Neuropathologie und Ätiologie fokaler Epilepsien - Blümcke, Ingmar; Hamer, Hajo (Der Nervenarzt, 2012)
In 2010 the International League against Epilepsy published a new classification of epilepsies. A major advance of this classification system is the acknowledgment of a genetic or pathologic-anatomic basis of epilepsy as important predictors of outcome (cause matters). This applies in particular to structural-metabolic lesions, which were frequently recognized in surgical specimens obtained from patients with drug-resistant focal epilepsy, i.e. hippocampal sclerosis, glioneuronal tumors, focal cortical dysplasias, vascular malformations, ischemia, intracerebral hemorrhage, glial scars or inflammation. A better understanding and classification of the etiopathology as well as the underlying molecular mechanisms will help to anticipate and appreciate the clinical course of a disease as well as to develop new and targeted drug treatment. Surgically available human brain tissue will be most helpful to support this approach but will also need careful neuropathological evaluation with accurate classification systems and use of terminology. © Springer-Verlag 2012.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Brain tumors; Dysplasia; Hippocampal sclerosis; Seizure

Neuroprotective dimethyl fumarate synergizes with immunomodulatory interferon beta to provide enhanced axon protection in autoimmune neuroinflammation - Reick, Christiane; Ellrichmann, Gisa; Thoene, Jan; Scannevin, Robert H.; Saft, Carsten; Linker, Ralf; Gold, Ralf (Experimental Neurology, 2014)
Despite recent advances in development of treatments for multiple sclerosis, there is still an unmet need for more effective and also safe therapies. Based on the modes of action of interferon-beta (IFN-?) and dimethyl fumarate (DMF), we hypothesized that anti-inflammatory and neuroprotective effects may synergize in experimental autoimmune encephalomyelitis (EAE).EAE was induced in C57BL/6 mice by immunization with MOG35-55-peptide. Murine IFN-? was injected s.c. every other day at 10.000IU, and DMF was provided at 15mg/kg by oral gavage twice daily. Control mice received PBS injections and were treated by oral gavage with the vehicle methylcellulose. Mice were scored daily by blinded observers and histological, FACS and cytokine studies were performed to further elucidate the underlying mechanism of action.Combination therapy significantly ameliorated EAE disease course in comparison to controls and monotherapy with IFN-?. Histological analyses showed a significant effect on axon preservation with almost twice as much axons present in inflamed lesions as compared to control. Remarkably, the effect on axonal preservation was more pronounced under combination therapy than with both monotherapies. Neither monotherapy nor combination therapy demonstrated modulation of cytokines and frequency of antigen presenting cells.Combination of IFN-? and DMF resulted in greater beneficial effects with improved tissue protection as compared to the respective monotherapies. Further combination studies of these safe therapies in human disease are warranted.
EVALuna2:22316

Neuropsychology and MRI correlates of neurodegeneration in SPG11 hereditary spastic paraplegia - Utz, Kathrin; Kohl, Zacharias; Marterstock, Dominique; Dörfler, Arnd; Winkler, Jürgen; Schmidt, Manuel; Regensburger, Martin (Orphanet Journal of Rare Diseases, 2022)
Background: SPG11-linked hereditary spastic paraplegia is characterized by multisystem neurodegeneration leading to a complex clinical and yet incurable phenotype of progressive spasticity and weakness. Severe cognitive symptoms are present in the majority of SPG11 patients, but a systematic and multidimensional analysis of the neuropsychological phenotype in a larger cohort is lacking. While thinning of the corpus callosum is a well-known structural hallmark observed in SPG11 patients, the neuroanatomical pattern of cortical degeneration is less understood. We here aimed to integrate neuropsychological and brain morphometric measures in SPG11. Methods: We examined the neuropsychological profile in 16 SPG11 patients using a defined neuropsychological testing battery. Long-term follow up testing was performed in 7 patients. Cortical and subcortical degeneration was analyzed using an approved, artificial intelligence based magnetic resonance imaging brain morphometry, comparing patients to established reference values and to matched controls. Results: In SPG11 patients, verbal fluency and memory as well as frontal-executive functions were severely impaired. Later disease stages were associated with a global pattern of impairments. Interestingly, reaction times correlated significantly with disease progression. Brain morphometry showed a significant reduction of cortical and subcortical parenchymal volume following a rostro-caudal gradient in SPG11. Whereas performance in memory tasks correlated with white matter damage, verbal fluency measures showed strong associations with frontal and parietal cortical volumes. Conclusions: The present data will help define neuropsychological and imaging read out parameters in early as well as in advanced clinical stages for future interventional trials in SPG11.
CRIS-Team Scopus Importer:2022-08-12
Keywords: Brain morphometry; Neuropsychology; Spastic paraplegia; SPG11; Verbal fluency

Neutral sphingomyelinase mediates the co-morbidity trias of alcohol abuse, major depression and bone defects - Kalinichenko, Liubov; Mühle, Christiane; Jia, Tianye; Anderheiden, Felix; Datz, Maria; Eberle, Anna-Lisa; Eulenburg, Volker; Granzow, Jonas; Hofer, Martin Jürgen; Hohenschild, Julia; Huber, Sabine; Kämpf, Stefanie; et al. (Molecular Psychiatry, 2021)
Mental disorders are highly comorbid and occur together with physical diseases, which are often considered to arise from separate pathogenic pathways. We observed in alcohol-dependent patients increased serum activity of neutral sphingomyelinase. A genetic association analysis in 456,693 volunteers found associations of haplotypes of SMPD3 coding for NSM-2 (NSM) with alcohol consumption, but also with affective state, and bone mineralisation. Functional analysis in mice showed that NSM controls alcohol consumption, affective behaviour, and their interaction by regulating hippocampal volume, cortical connectivity, and monoaminergic responses. Furthermore, NSM controlled bone–brain communication by enhancing osteocalcin signalling, which can independently supress alcohol consumption and reduce depressive behaviour. Altogether, we identified a single gene source for multiple pathways originating in the brain and bone, which interlink disorders of a mental–physical co-morbidity trias of alcohol abuse—depression/anxiety—bone disorder. Targeting NSM and osteocalcin signalling may, thus, provide a new systems approach in the treatment of a mental–physical co-morbidity trias.
CRIS-Team Scopus Importer:2021-10-08

Neutrophil-to-lymphocyte ratio as an independent predictor for unfavorable functional outcome in aneurysmal subarachnoid hemorrhage - Giede-Jeppe, Antje; Reichl, Jonathan; Sprügel, Maximilian; Lücking, Hannes; Hölter, Philip; Eyüpoglu, Ilker Yasin; Kuramatsu, Joji; Huttner, Hagen; Gerner, Stefan (Journal of Neurosurgery, 2019)
OBJECTIVEStroke-associated immunosuppression and inflammation are increasingly recognized as factors triggering infections and thus potentially influencing outcome after stroke. Several studies have demonstrated that elevated neutrophil-to-lymphocyte ratio (NLR) is a significant predictor of adverse outcomes for patients with ischemic stroke or intracerebral hemorrhage. Thus far, in patients with subarachnoid hemorrhage the association between NLR and outcome is insufficiently established. The authors sought to investigate the association between NLR on admission and functional outcome in aneurysmal subarachnoid hemorrhage (aSAH).METHODSThis observational study included all consecutive aSAH patients admitted to a German tertiary center over a 5-year period (2008-2012). Data regarding patient demographics and clinical, laboratory, and in-hospital measures, as well as neuroradiological data, were retrieved from institutional databases. Functional outcome was assessed at 3 and 12 months using the modified Rankin Scale (mRS) score and categorized into favorable (mRS score 0-2) and unfavorable (mRS score 3-6). Patients' radiological and laboratory characteristics were compared between aSAH patients with favorable and those with unfavorable outcome at 3 months. In addition, multivariate analysis was conducted to investigate parameters independently associated with favorable outcome. Receiver operating characteristic (ROC) curve analysis was undertaken to identify the best cutoff for NLR to discriminate between favorable and unfavorable outcome in these patients. To account for imbalances in baseline characteristics, propensity score matching was carried out to assess the influence of NLR on outcome measures.RESULTSOverall, 319 patients with aSAH were included. Patients with unfavorable outcome at 3 months were older, had worse clinical status on admission (Glasgow Coma Scale score and Hunt and Hess grade), greater amount of subarachnoidal and intraventricular hemorrhage (modified Fisher Scale grade and Graeb score), and higher rates of infectious complications (pneumonia and sepsis). A significantly higher NLR on admission was observed in patients with unfavorable outcome according to mRS score (median [IQR] NLR 5.8 [3.0-10.0] for mRS score 0-2 vs NLR 8.3 [4.5-12.6] for mRS score 3-6; p < 0.001). After adjustments, NLR on admission remained a significant predictor for unfavorable outcome in SAH patients (OR [95% CI] 1.014 [1.001-1.027]; p = 0.028). In ROC analysis, an NLR of 7.05 was identified as the best cutoff value to discriminate between favorable and unfavorable outcome (area under the curve = 0.614, p < 0.001, Youden's index = 0.211; mRS score 3-6: 94/153 [61.4%] for NLR ≥ 7.05 vs 67/166 [40.4%] for NLR < 7.05; p < 0.001). Subanalysis of patients with NLR levels ≥ 7.05 vs < 7.05, performed using 2 propensity score-matched cohorts (n = 133 patients in each group), revealed an increased proportion of patients with unfavorable functional outcome at 3 months in patients with NLR ≥ 7.05 (mRS score 3-6 at 3 months: NLR ≥ 7.05 82/133 [61.7%] vs NLR < 7.05 62/133 [46.6%]; p = 0.014), yet without differences in mortality at 3 months (NLR ≥ 7.05 37/133 [27.8%] vs NLR < 7.05 27/133 [20.3%]; p = 0.131).CONCLUSIONSAmong aSAH patients, NLR represents an independent parameter associated with unfavorable functional outcome. Whether the impact of NLR on functional outcome is related to preexisting comorbidities or represents independent causal relationships in the context of stroke-associated immunosuppression should be investigated in future studies.
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Neutrophil-to-Lymphocyte Ratio Is an Independent Predictor for In-Hospital Mortality in Spontaneous Intracerebral Hemorrhage - Giede-Jeppe, Antje; Bobinger, Tobias; Gerner, Stefan; Sembill, Jochen; Sprügel, Maximilian; Beuscher, Vanessa D.; Lücking, Hannes; Kuramatsu, Joji; Huttner, Hagen; Hölter, Philip (Cerebrovascular Diseases, 2017)
Stroke-associated immunosuppression and inflammation are increasingly recognized as factors that trigger infections and thus, potentially influence the outcome after stroke. Several studies demonstrated that elevated neutrophil-to-lymphocyte ratio (NLR) is a significant predictor of adverse outcomes in patients with ischemic stroke. However, little is known about the impact of NLR on short-term mortality in intracerebral hemorrhage (ICH).This observational study included 855 consecutive ICH-patients. Patient demographics, clinical, laboratory, and in-hospital measures as well as neuroradiological data were retrieved from institutional databases. Functional 3-months-outcome was assessed and categorized as favorable (modified Rankin Scale [mRS] 0-3) and unfavorable (mRS 4-6). We (i) studied the natural course of NLR in ICH, (ii) analyzed parameters associated with NLR on admission (NLROA), and (iii) evaluated the clinical impact of NLR on mortality and functional outcome.The median NLROA of the entire cohort was 4.66 and it remained stable during the entire hospital stay. Patients with NLR >=4.66 showed significant associations with poorer neurological status (National Institute of Health Stroke Scale [NIHSS] 18 [9-32] vs. 10 [4-21]; p < 0.001), larger hematoma volume on admission (17.6 [6.9-47.7] vs. 10.6 [3.8-31.7] mL; p = 0.001), and more frequently unfavorable outcome (mRS 4-6 at 3 months: 317/427 [74.2%] vs. 275/428 [64.3%]; p = 0.002). Patients with an NLR under the 25th percentile (NLR <2.606) - compared to patients with NLR >2.606 - presented with a better clinical status (NIHSS 12 [5-21] vs. 15 [6-28]; p = 0.005), lower hematoma volumes on admission (10.6 [3.6-30.1] vs. 15.1 [5.7-42.3] mL; p = 0.004) and showed a better functional outcome (3 months mRS 0-3: 82/214 [38.3%] vs. 185/641 [28.9%]; p = 0.009). Patients associated with high NLR (>=8.508 = above 75th-percentile) showed the worst neurological status on admission (NIHSS 21 [12-32] vs. 12 [5-23]; p < 0.001), larger hematoma volumes (21.0 [8.6-48.8] vs. 12.2 [4.1-34.9] mL; p < 0.001), and higher proportions of unfavorable functional outcome at 3 months (mRS 4-6: 173/214 vs. 418/641; p < 0.001). Further, NLR was linked to more frequently occurring infectious complications (pneumonia 107/214 vs. 240/641; p = 0.001, sepsis: 78/214 vs. 116/641; p < 0.001), and increased c-reactive-protein levels on admission (p < 0.001; R2 = 0.064). Adjusting for the above-mentioned baseline confounders, multivariable logistic analyses revealed independent associations of NLROA with in-hospital mortality (OR 0.967, 95% CI 0.939-0.997; p = 0.029).NLR represents an independent parameter associated with increased mortality in ICH patients. Stroke physicians should focus intensely on patients with increased NLR, as these patients appear to represent a population at risk for infectious complications and increased short-mortality. Whether these patients with elevated NLR may benefit from a close monitoring and specially designed therapies should be investigated in future studies.
EVALuna2:22531

Neutrophil-to-lymphocyte ratio is associated with increased cerebral blood flow velocity in acute bacterial meningitis - Giede-Jeppe, Antje; Atay, Selim; Koehn, Julia; Mrochen, Anne; Lücking, Hannes; Hölter, Philip; Volbers, Bastian; Huttner, Hagen B.; Hueske, Lena; Bobinger, Tobias (Scientific Reports, 2021)
In community-acquired bacterial meningitis (CABM) intracranial vascular alterations are devastating complications which are triggered by neuroinflammation and result in worse clinical outcome. The Neutrophil-to-Lymphocyte ratio (NLR) represents a reliable parameter of the inflammatory response. In this study we analyzed the association between NLR and elevated cerebral blood flow velocity (CBFv) in CABM-patients. This study included all (CABM)-patients admitted to a German tertiary center between 2006 and 2016. Patients’ demographics, in-hospital measures, neuroradiological data and clinical outcome were retrieved from institutional databases. CBFv was assessed by transcranial doppler (TCD). Patients’, radiological and laboratory characteristics were compared between patients with/without elevated CBFv. Multivariate-analysis investigated parameters independently associated with elevated CBFv. Receiver operating characteristic(ROC-)curve analysis was undertaken to identify the best cut-off for NLR to discriminate between increased CBFv. 108 patients with CABM were identified. 27.8% (30/108) showed elevated CBFv. Patients with elevated CBFv and normal CBFv, respectively had a worse clinical status on admission (Glasgow Coma Scale: 12 [9–14] vs. 14 [11–15]; p = 0.005) and required more often intensive care (30/30 [100.0%] vs. 63/78 [80.8%]; p = 0.01).The causative pathogen was S. pneumoniae in 70%. Patients with elevated CBFv developed more often cerebrovascular complications with delayed cerebral ischemia (DCI) within hospital stay (p = 0.031). A significantly higher admission-NLR was observed in patients with elevated CBFv (median [IQR]: elevated CBFv:24.0 [20.4–30.2] vs. normal CBFv:13.5 [8.4–19.5]; p < 0.001). Multivariate analysis, revealed NLR to be significantly associated with increased CBFv (Odds ratio [95%CI] 1.042 [1.003–1.084]; p = 0.036). ROC-analysis identified a NLR of 20.9 as best cut-off value to discriminate between elevated CBFv (AUC = 0.713, p < 0.0001, Youden's Index = 0.441;elevated CBFv: NLR ≥ 20.9 19/30[63.5%] vs. normal CBFv: NLR > 20.9 15/78[19.2%]; p < 0.001). Intracranial vascular complications are common among CABM-patients and are a risk factor for unfavorable outcome at discharge. Elevated NLR is independently associated with high CBFv and may be useful in predicting patients’ prognosis.
CRIS-Team Scopus Importer:2021-06-18

New aspects in the field of epilepsy - Rosenow, F.; Klein, K. M.; Strzelczyk, A.; Hamer, Hajo; Menzler, K.; Bauer, S.; Knake, S. (Der Nervenarzt, 2014)
Regarding epilepsy several new developments can be reported. The International League Against Epilepsy (ILAE) has suggested a new definition of epilepsy, for the first time including a definition of epilepsy resolution. Progress in the diagnosis relates to new genetic findings, improvements in magnetic resonance imaging (MRI) and the increasing use of stereo electroencephalograms (sEEG). Regarding treatment there are new clinically relevant data on the pathophysiology and prevention of sudden unexpected death in epilepsy (SUDEP). Zonisamide has been approved by the European Medicines Agency (EMA) for monotherapy in adults with focal seizures and combination therapy in children aged >= 6 years. Retigabin and perampanel have been approved but are currently taken off the market in Germany (only) because the Gemeinsamer Bundesausschuss (GBA, Joint Federal Committee) did not find any additional therapeutic value as compared to lamotrigine due to a lack of data. A decision regarding a new application for perampanel is pending. Regarding surgical treatment novel ablation techniques (e.g. stereotactic radiofrequency and laser ablation as well as focussed ultrasound ablation) and brain stimulation paradigms are under investigation. Experimental studies, generously supported by the European Union (EU) and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) are focusing on (opto-)genetic (e.g. using lentoviral transfection), epigenetic (e.g. micro-RNA-related) approaches and on the investigation of neuronal micronetworks.
EVALuna2:22382

New CaV1.2 channelopathy with high-functioning autism, affective disorder, severe dental enamel defects, a short QT interval, and a novel cacna1c loss-of-function mutation - Endres, Dominique; Decher, Niels; Röhr, Isabell; Vowinkel, Kirsty; Domschke, Katharina; Komlosi, Katalin; Tzschach, Andreas; Gläser, Birgitta; Schiele, Miriam A.; Runge, Kimon; Süß, Patrick; Schuchardt, Florian; et al. (International Journal of Molecular Sciences, 2020)
Complex neuropsychiatric-cardiac syndromes can be genetically determined. For the first time, the authors present a syndromal form of short QT syndrome in a 34-year-old German male patient with extracardiac features with predominant psychiatric manifestation, namely a severe form of secondary high-functioning autism spectrum disorder (ASD), along with affective and psychotic exacerbations, and severe dental enamel defects (with rapid wearing off his teeth) due to a heterozygous loss-of-function mutation in the CACNA1C gene (NM_000719.6: c.2399A > C; p.Lys800Thr). This mutation was found only once in control databases; the mutated lysine is located in the Cav1.2 calcium channel, is highly conserved during evolution, and is predicted to affect protein function by most pathogenicity prediction algorithms. L-type Cav1.2 calcium channels are widely expressed in the brain and heart. In the case presented, electrophysiological studies revealed a prominent reduction in the current amplitude without changes in the gating behavior of the Cav1.2 channel, most likely due to a trafficking defect. Due to the demonstrated loss of function, the p.Lys800Thr variant was finally classified as pathogenic (ACMG class 4 variant) and is likely to cause a newly described Cav1.2 channelopathy.
CRIS-Team Scopus Importer:2020-11-27
Keywords: Autism; CACNA1C; CaV1.2; Dental enamel defect; Short QT syndrome

New Perspectives for Spinal Cord Stimulation in Parkinson’s Disease-Associated Gait Impairment: A Systematic Review - Seufert, Christian; Borutta, Matthias; Regensburger, Martin; Zhao, Yining; Kinfe, Thomas Mehari (Biomedicines, 2024)
Parkinson’s Disease is a neurodegenerative disorder manifesting itself as a hypokinetic movement impairment with postural instability and gait disturbance. In case of failure and/or limited response, deep brain stimulation has been established as an alternative and effective treatment modality. However, a subset of PD patients with gait impairment represents a therapeutic challenge. A systematic review (2000–2023) was performed using PubMed, Embase, Web of Science, Scopus, and Cochrane Library databases to determine the efficacy, stimulation waveform/parameters, spine level, and outcome measures of spinal cord stimulation using different waveforms in PD patients with and without chronic pain. Spinal cord stimulation responsiveness was assessed within the pre-defined follow-up period in three groups (short-term follow-up = 0–3 months; intermediate follow-up = 3–12 months; and long-term follow-up = more than 12 months). In addition, we briefly outline alternative neurostimulation therapies and the most recent developments in closed-loop spinal cord stimulation relevant to PD. In summary, 18 publications and 70 patients from uncontrolled observational trials were included, with low-quality evidence and conflicting findings. First and foremost, the currently available data do not support the use of spinal cord stimulation to treat PD-related gait disorders but have confirmed its usefulness for PD-associated chronic pain.
CRIS-Team Scopus Importer:2024-09-06
Keywords: deep brain stimulation; freezing of gait; gait dysfunction; motor symptoms; movement disorders; neurodegenerative disorders; neuromodulation; neurostimulation; Parkinson’s Disease; spinal cord stimulation

New role for the (pro)renin receptor in T-cell development - Geisberger, Sabrina; Maschke, Ulrike; Gebhardt, Matthias; Kleinewietfeld, Markus; Manzel, Arndt; Linker, Ralf; Chidgey, Ann; Dechend, Ralf; Nguyen, Genevieve; Daumke, Oliver; Muller, Dominik N.; Wright, Mark D.; et al. (Blood, 2015)
The (pro)renin receptor (PRR) was originally thought to be important for regulating blood pressure via the renin-angiotensin system. However, it is now emerging that PRR has instead a generic role in cellular development. Here, we have specifically deleted PRR from T cells. T-cell-specific PRR-knockout mice had a significant decrease in thymic cellularity, corresponding with a 100-fold decrease in the number of CD4(+) and CD8(+) thymocytes, and a large increase in double-negative (DN) precursors. Gene expression analysis on sorted DN3 thymocytes indicated that PRR-deficient thymocytes have perturbations in key cellular pathways essential at the DN3 stage, including transcription and translation. Further characterization of DN T-cell progenitors leads us to propose that PRR deletion affects thymocyte survival and development at multiple stages; from DN3 through to DN4, double-positive, and single-positive CD4 and CD8. Our study thus identifies a new role for PRR in T-cell development.
EVALuna2:22337

Nfat/calcineurin signaling promotes oligodendrocyte differentiation and myelination by transcription factor network tuning. - Weider, Matthias; Starost, Laura Julia; Groll, Katharina; Küspert, Melanie; Sock, Elisabeth; Wedel, Miriam; Fröb, Franziska; Schmitt, Christian; Baroti, Tina; Hartwig, Anna; Hillgärtner, Simone; Piefke, Sandra; et al. (Nature Communications, 2018)
Oligodendrocytes produce myelin for rapid transmission and saltatory conduction of action potentials in the vertebrate central nervous system. Activation of the myelination program requires several transcription factors including Sox10, Olig2, and Nkx2.2. Functional interactions among them are poorly understood and important components of the regulatory network are still unknown. Here, we identify Nfat proteins as Sox10 targets and regulators of oligodendroglial differentiation in rodents and humans. Overall levels and nuclear fraction increase during differentiation. Inhibition of Nfat activity impedes oligodendrocyte differentiation in vitro and in vivo. On a molecular level, Nfat proteins cooperate with Sox10 to relieve reciprocal repression of Olig2 and Nkx2.2 as precondition for oligodendroglial differentiation and myelination. As Nfat activity depends on calcium-dependent activation of calcineurin signaling, regulatory network and oligodendroglial differentiation become sensitive to calcium signals. NFAT proteins are also detected in human oligodendrocytes, downregulated in active multiple sclerosis lesions and thus likely relevant in demyelinating disease.
UnivIS-Import:2018-09-11:Pub.2018.med.IB.LPCIPDBI.nfatca

Nimodipine fosters remyelination in a mouse model of multiple sclerosis and induces microglia-specific apoptosis - Schampel, Andrea; Volovitch, Oleg; Koeniger, Tobias; Scholz, Claus-Juergen; Joerge, Stefanie; Linker, Ralf; Wischmeyer, Erhard; Wunsch, Marie; Hell, Johannes W.; Erguen, Sueleyman; Kuerten, Stefanie (Proceedings of the National Academy of Sciences of the United States of America, 2017)
Despite continuous interest in multiple sclerosis (MS) research, there is still a lack of neuroprotective strategies, because the main focus has remained on modulating the immune response. Here we performed in-depth analysis of neurodegeneration in experimental autoimmune encephalomyelitis (EAE) and in in vitro studies regarding the effect of the well-established L-type calcium channel antagonist nimodipine. Nimodipine treatment attenuated clinical EAE and spinal cord degeneration and promoted remyelination. Surprisingly, we observed calcium channel-independent effects on microglia, resulting in apoptosis. These effects were cell-type specific and irrespective of microglia polarization. Apoptosis was accompanied by decreased levels of nitric oxide (NO) and inducible NO synthase (iNOS) in cell culture as well as decreased iNOS and reactive oxygen species levels in EAE. In addition, increased numbers of Olig2(+)APC(+) oligodendrocytes were detected. Overall, nimodipine application seems to generate a favorable environment for regenerative processes and therefore could be a treatment option for MS, because it combines features of immunomodulation with beneficial effects on neuroregeneration.
EVALuna2:22492

No evidence of disease activity status over 3 years in a real-world cohort of relapsing remitting MS patients in Germany - Huhn, Konstantin; Senger, Daniela; Utz, Kathrin S.; Schmidt, Manuel; Fröhlich, Katharina; Waschbisch, Anne; Seifert, Frank; Dörfler, Arnd; Lee, De-Hyung; Linker, Ralf A. (Multiple Sclerosis and Related Disorders, 2019)
BACKGROUND: Over the last decade, therapy of relapsing remitting multiple sclerosis (RRMS) has evolved with the approval of several new treatment concepts. Thus, treatment goals have become more ambitious aiming at "no evidence of disease activity" (NEDA). As NEDA-3, this concept comprises freedom of clinical disease progression and relapses as well as inflammatory MRI activity. So far, data on NEDA status mainly stem from post-hoc analyses of drug approval studies. Yet, less is known about the significance of NEDA in "real-world" clinical settings. Hence, our study aims at investigation of NEDA in a heterogeneous cohort of relapsing MS patients. METHODS: This is a retrospective single-center study at the Department of Neurology of the University Hospital Erlangen, Germany, including data of 306 patients with relapsing forms of MS (RMS) or clinical isolated syndrome (CIS) from 2009 to 2016. Inclusion required sufficient clinical information and in house cranial MRI follow-up data sets at baseline and at follow-up after one year with a potential extension to two and three year follow-up, if possible. NEDA-3 status, its correlation to clinical features, associated medication and NEDA failure (EDA) were analyzed. RESULTS: In a cohort of RMS patients at the early stages of the disease (median EDSS 1.5, mean disease duration 30 months) at baseline, 45% retained NEDA-3 status after one year. This percentage decreased in year two (29%) and three (21%) of follow-up. MRI criteria were responsible for loss of NEDA status in 64% of cases and CIS patients were more likely to sustain NEDA status. Therapy with monoclonal antibodies appeared superior in sustaining NEDA status as compared to injectables or oral treatment options. DISCUSSION: In our real-world analysis, we confirm the potential of NEDA for the evaluation and surveillance of MS disease activity, progression and therapy efficacy. Despite highly efficient immunomodulatory treatment, NEDA-3 was only preserved in a minority of patients. Monoclonal antibodies may yield best NEDA rates. Further studies are warranted to evaluate the value of the NEDA concept in real-world settings beyond standardized clinical studies.
EVALuna2:36277

Nonadherence to antiepileptic drugs in Germany: A retrospective, population-based study - Gollwitzer, Stephanie; Kostev, Karel; Hagge, Mareike; Lang, Johannes; Graf, Wolfgang; Hamer, Hajo (Neurology, 2016)
To assess the effect of patient and drug characteristics on medication adherence in people with epilepsy (PWE) in a large cohort representative of the German population.Information was obtained from the Disease Analyzer database that collects anonymous demographic and medical data from practice computer systems throughout Germany. From 2010 to 2013, adult PWE were retrospectively analyzed regarding demographic characteristics, comorbidities, and treatment with antiepileptic drugs (AED). Adherence was measured using the medication possession ratio (MPR). Individuals with an MPR <80% were classified as nonadherent. Multivariate regression models were applied to assess the association of different factors with adherence by calculating adjusted odds ratios (OR) with 95% confidence intervals.A total of 31,317 PWE were included. The mean MPR was 81.1% (SD 25.7%) with 64.7% of patients showing good adherence (MPR >80%). Patient-related factors associated with good adherence to AED treatment were West German residence (OR 1.23, p < 0.0001) and learning disability (OR 1.80, p < 0.0001). Adherence was higher in patients treated with new than old (OR 1.52, p < 0.0001) and branded than generic AED (OR 1.44, p < 0.0001). Among the most common AED, levetiracetam achieved best adherence (OR 2.85, p < 0.0001), valproate lowest. Two or more daily dosages reduced adherence (TID vs QD: OR 0.84, p = 0.005; BID vs QD: OR 0.86, p = 0.011).One third of PWE treated with AED in Germany showed poor adherence, which was related to demographic characteristics and drug properties. Administration of new, well-tolerated drugs in simple dosage regimens improved AED compliance.
EVALuna2:22472

Noncompliance of patients with driving restrictions due to uncontrolled epilepsy - Willems, Laurent M.; Reif, Philipp S.; Knake, Susanne; Hamer, Hajo; Willems, Constantin; Kraemer, Guenter; Rosenow, Felix; Strzelczyk, Adam (Epilepsy & Behavior, 2019)
Epilepsies are a common and chronic neurological disorder characterized by sustained risk of recurrent seizures. Because of paroxysmal and often unpredictable occurrence of seizures, patients with uncontrolled epilepsy are subject to disease-specific restrictions in daily life, such as their career choice or specific work limitations. According to German law and many other European and international guidelines, driving is strictly prohibited in patients with uncontrolled epilepsy so as to increase active and passive safety in public road traffic. Nevertheless. a significant percentage of patients probably do not comply with these legal restrictions and drive on a regular basis. For this study, we analyzed a representative German cohort with 302 patients (mean age: 45.0 years +/- 16.4; 48% male) with established epilepsy to identify the number of patients driving without permission. Overall, 58.6% (n = 177) of patients had a driving license, 71.1% (n 69/97) of patients were in seizure remission, and 52.7% (n = 108/205) of patients had uncontrolled epilepsy. Among patients in seizure remission, 54.6% (n = 53/97) reported regular driving while, among patients with uncontrolled epilepsy, 15.1% (n = 31/205) reported driving on a regular basis. No patient in the cohort stated driving without a valid license. Permanent employment, freelance work, the absence of a relevant disability, and living alone were identified as significant risk factors, which underlines the already existing evidence for the importance of a possible restricted access to the labor market as motive for disregarding legal driving restrictions.
CRIS-Team WoS Importer:2019-04-04

Non-Inferiority Trials in Stroke Research: What Are They, and How Should We Interpret Them? - Li, Linxin; Lioutas, Vasileios Arsenios; Akyea, Ralph K.; Gerner, Stefan; Lau, Kui Kai; Ramage, Emily; Katsanos, Aristeidis H.; Howard, George; Bath, Philip M. (Journal of Stroke, 2025)
Randomized clinical trials are important in both clinical and academic stroke communities with increasing numbers of new design concepts emerging. One of the “less traditional” designs that have gained increasing interest in the last decade is non-inferiority trials. Whilst the concept might appear straightforward, the design and interpretation of non-inferiority trials can be challenging. In this review, we will use exemplars from clinical trials in the stroke field to provide an overview of the advantages and limitations of non-inferiority trials and how they should be interpreted in stroke research.
CRIS-Team Scopus Importer:2025-02-28
Keywords: Clinical trial; Methodology; Non-inferiority; Stroke; Trial design

Noninvasive Collateral Flow Velocity Imaging in Acute Ischemic Stroke: Intraindividual Comparison of 4D-CT Angiography with Digital Subtraction Angiography - Mühlen, Iris; Kloska, Stephan P.; Gölitz, Philipp; Breuer, Lorenz; Ditt, Hendrik; Dörfler, Arnd; Hölter, Philip (Röfo-Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2019)
Purpose The collateral status can be defined not only by its morphological extent but also by the velocity of collateral filling characterized by the relative filling time delay (rFTD). The aim of our study was to compare different methods of noninvasive visualization of rFTD derived from 4D-CT angiography (4D-CTA) with digital substraction angiography (DSA) and to investigate the correlation between functional and morphological collateral status on timing-invariant CTA.
CRIS-Team WoS Importer:2019-09-20

Non-invasive EEG evaluation in epilepsy diagnosis - Rosenow, Felix; Klein, Karl Martin; Hamer, Hajo (Expert review of neurotherapeutics, 2015)
The EEG is an invaluable tool in the diagnosis of epilepsy which guides clinical management. It helps to determine if attacks are of epileptic origin, allows the estimation of the recurrence risk after a first seizure, aids in the diagnosis of the epilepsy syndrome and represents the gold standard in the presurgical evaluation of epilepsy. The EEG can also detect subclinical seizures as a cause of coma. In this review we discuss the sensitivity and specificity of the EEG, present the EEG findings and their significance in different epilepsy syndromes including focal and generalized epilepsies and describe the application of activation procedures.
EVALuna2:22395

Non-invasive optoacoustic imaging of glycogen-storage and muscle degeneration in late-onset Pompe disease. - Tan, Lina; Zschüntzsch, Jana; Meyer, Stefanie; Stobbe, Alica; Bruex, Hannah; Regensburger, Adrian; Claßen, Merle; Alves, Frauke; Jüngert, Jörg; Rother, Ulrich; Li, Yi; Danko, Vera; et al. (Nature Communications, 2024)
Pompe disease (PD) is a rare autosomal recessive glycogen storage disorder that causes proximal muscle weakness and loss of respiratory function. While enzyme replacement therapy (ERT) is the only effective treatment, biomarkers for disease monitoring are scarce. Following ex vivo biomarker validation in phantom studies, we apply multispectral optoacoustic tomography (MSOT), a laser- and ultrasound-based non-invasive imaging approach, in a clinical trial (NCT05083806) to image the biceps muscles of 10 late-onset PD (LOPD) patients and 10 matched healthy controls. MSOT is compared with muscle magnetic resonance imaging (MRI), ultrasound, spirometry, muscle testing and quality of life scores. Next, results are validated in an independent LOPD patient cohort from a second clinical site. Our study demonstrates that MSOT enables imaging of subcellular disease pathology with increases in glycogen/water, collagen and lipid signals, providing higher sensitivity in detecting muscle degeneration than current methods. This translational approach suggests implementation in the complex care of these rare disease patients.
EVALuna2:571098

Non-professional Phagocytes can phagocytize Necrotic Cells at any Stage of the Cell Cycle - Hofmann, Andrea; Seeberg, Jacob; Fietkau, Rainer; Distel, Luitpold (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Non-specific gastrointestinal features: Could it be Fabry disease? - Hilz, Max-Josef; Arbustini, Eloisa; Dagna, Lorenzo; Gasbarrini, Antonio; Goizet, Cyril; Lacombe, Didier; Liguori, Rocco; Manna, Raffaele; Politei, Juan; Spada, Marco; Burlina, Alessandro (Digestive and Liver Disease, 2018)
Non-specific gastrointestinal symptoms, including pain, diarrhoea, nausea, and vomiting, can be the first symptoms of Fabry disease. They may suggest more common disorders, e.g. irritable bowel syndrome or inflammatory bowel disease. The confounding clinical presentation and rarity of Fabry disease often cause long diagnostic delays and multiple misdiagnoses. Therefore, specialists involved in the clinical evaluation of non-specific upper and lower gastrointestinal symptoms should recognize Fabry disease as a possible cause of the symptoms, and should consider Fabry disease as a possible differential diagnosis. When symptoms or family history suggest Fabry disease, in men, low alpha-galactosidase A enzyme levels, and in women, specific Fabry mutations confirm the diagnosis. In addition to symptomatic treatments, disease-specific enzyme replacement therapy with recombinant human alpha-galactosidase A enzyme or chaperone therapy (migalastat) in patients with amenable mutations can improve the disease, including gastrointestinal symptoms, and should be initiated as early as possible after Fabry disease has been confirmed; starting enzyme replacement therapy at as young an age as possible after diagnosis improves long-term clinical outcomes. Improved diagnostic tools, such as a modified gastrointestinal symptom rating scale, may facilitate diagnosing Fabry disease in patients with gastrointestinal symptoms of unknown cause and thus assure timely initiation of disease-specific treatment.
EVALuna2:201940

No sex differences in long-term functional outcome after intracerebral hemorrhage - De Ridder, Inger; Kuramatsu, Joji; Gerner, Stefan; Madzar, Dominik; Lücking, Hannes; Kloska, Stephan; Dippel, Diederik; Schwab, Stefan; Huttner, Hagen (International Journal of Stroke, 2017)
Background There is conflicting evidence about the influence of sex on outcome after spontaneous intracerebral hemorrhage (sICH) and the majority of the research focused on mortality and short-term outcome only. We investigated sex differences in long-term functional outcome after sICH. Methods We used data from a prospective hospital registry and included all consecutive patients with ICH admitted to our institution between January 2006 and July 2014. Functional outcome was assessed by modified Rankin Scale evaluated 3 and 12 months after ICH. We explored the influence of sex on long-term functional outcome using multivariable regression models and additionally by means of propensity score matching. Results We analyzed 823 patients, of whom 380 (46%) women. Women were on average three years older (p < 0.001), men had more often deep hematomas (p = 0.01). Unadjusted mortality rates were significantly increased in women at three months (42% vs. 35%; odds ratio (OR): 1.35; 95% confidence interval (CI): 1.02-1.80). After adjusting for baseline prognostic factors there were no differences between men and women in short- and long-term mortality (OR = 1.01; 95% CI = 0.66-1.54 and OR = 1.04; 95%CI = 0.69-1.57, respectively) and short- and long-term unfavorable outcome (OR = 1.02; 95%CI = 0.67-1.55 and OR = 0.96; 95% CI = 0.62-1.48, respectively). Conclusion We found no sex-related differences in long-term functional outcome in patients with sICH. The apparently worse functional outcome in women can be explained by differences in age.
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Novel Antineuronal Autoantibodies With Somatodendritic Staining Pattern in a Patient With Autoimmune Psychosis - Endres, Dominique; Rauer, Sebastian; Pschibul, Alexander; Süß, Patrick; Venhoff, Nils; Runge, Kimon; Feige, Bernd; Denzel, Dominik; Nickel, Kathrin; Schweizer, Tina; Maier, Simon; Egger, Karl; et al. (Frontiers in Psychiatry, 2020)
Background: Autoimmune encephalitis, such as anti-NMDA-receptor encephalitis, typically presenting with subacute onset of neuropsychiatric symptoms, can be detected by antineuronal autoantibodies or inflammatory changes in the cerebrospinal fluid (CSF), as well as pathological alterations in electroencephalography (EEG), magnetic resonance imaging (MRI), or [18F]fluorodeoxyglucose positron emission tomography (FDG PET). For patients with predominant psychotic symptoms, the term autoimmune psychosis was proposed. Here, the authors present the case of a patient with probable autoimmune psychosis associated with unknown antineuronal antibodies. Case Presentation: A 18-year-old male patient with preexisting autism spectrum disorder developed a severe catatonic syndrome over 2.5 years. The MRI showed normal findings, the EEG depicted intermittent slowing, and the independent component analyses showed additional sharp spikes. However, FDG PET, the basic laboratory analysis and testing of the serum/CSF for well-characterized antineuronal autoantibodies were unsuspicious. The serum and CSF “tissue-based assay” using indirect immunofluorescence on unfixed murine brain tissue revealed antineuronal autoantibodies against an unknown epitope in granule cells in the cerebellum and to neurites of hippocampal interneurons with a somatodendritic staining pattern. The immunosuppressive treatment with high-dose glucocorticoids, plasma exchange, and rituximab led to partial improvement. Conclusion: The patient probably suffered from autoantibody-associated autoimmune psychosis. The special features of the case were that the patient (1) presented with mostly inconspicuous basic diagnostics, except for the altered EEG in combination with the detection of CSF autoantibodies directed against a currently unknown epitope, (2) experienced an isolated and long-lasting psychotic course, and (3) had pre-existing autism spectrum disorder. The detection of a probable autoimmune pathophysiology in such cases seems important, as it offers new and more causal immunosuppressive treatment alternatives.
CRIS-Team Scopus Importer:2020-09-04
Keywords: antibodies; autoimmune encephalitis; autoimmune psychosis; catatonia; encephalopathy; schizophrenia

Novel Biallelic CTSD Gene Variants Cause Late-Onset Ataxia and Retinitis Pigmentosa - Regensburger, Martin; Minakaki, Georgia; Kettwig, Matthias; Huchzermeyer, Cord; Eisenhut, Felix; Haack, Tobias B.; Kohl, Zacharias; Winkler, Jürgen (Movement Disorders, 2020)
CRIS-Team Scopus Importer:2020-05-29

Novel Homozygous FA2H Variant Causing the Full Spectrum of Fatty Acid Hydroxylase-Associated Neurodegeneration (SPG35) - German, Alexander; Jukic, Jelena; Laner, Andreas; Arnold, Philipp; Socher, Eileen; Mennecke, Angelika; Schmidt, Manuel; Winkler, Jürgen; Abicht, Angela; Regensburger, Martin (Genes, 2023)
Fatty acid hydroxylase-associated neurodegeneration (FAHN/SPG35) is caused by pathogenic variants in FA2H and has been linked to a continuum of specific motor and non-motor neurological symptoms, leading to progressive disability. As an ultra-rare disease, its mutational spectrum has not been fully elucidated. Here, we present the prototypical workup of a novel FA2H variant, including clinical and in silico validation. An 18-year-old male patient presented with a history of childhood-onset progressive cognitive impairment, as well as progressive gait disturbance and lower extremity muscle cramps from the age of 15. Additional symptoms included exotropia, dystonia, and limb ataxia. Trio exome sequencing revealed a novel homozygous c.75C>G (p.Cys25Trp) missense variant in the FA2H gene, which was located in the cytochrome b5 heme-binding domain. Evolutionary conservation, prediction models, and structural protein modeling indicated a pathogenic loss of function. Brain imaging showed characteristic features, thus fulfilling the complete multisystem neurodegenerative phenotype of FAHN/SPG35. In summary, we here present a novel FA2H variant and provide prototypical clinical findings and structural analyses underpinning its pathogenicity.<br
Keywords: hereditary spastic paraplegia; SPG35; FA2H; FAHN; genetic variant modeling

Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation - Andlauer, Till F. M.; Buck, Dorothea; Antony, Gisela; Bayas, Antonios; Bechmann, Lukas; Berthele, Achim; Chan, Andrew; Gasperi, Christiane; Gold, Ralf; Graetz, Christiane; Haas, Juergen; Hecker, Michael; et al. (Science Advances, 2016)
We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis.
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NOVEL MUTATIONS AND FINDINGS IN A COHORT OF MCLEOD NEUROACANTHOCYTOSIS, AN X-LINKED HD PHENOCOPY - Peikert, Kevin; Schlotter-Weigel, Beate; Montagnese, Federica; Reilich, Peter; Saft, Carsten; Marxreiter, Franz; Kohl, Zacharias; Evers, Stefan; Von Kalckreuth, Wolfgang; Buhmann, Carsten; Mayer, Beate; Walther, Ernst; et al. (JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2021)
Background McLeod syndrome (MLS) is an ultra-rare neurodegenerative X-linked disease caused by mutations in the XK gene, classified as one of the core neuroacanthocytosis syndromes. Together with the clinically very similar chorea-acanthocytosis it belongs to the heterogeneous group of ‘Huntington’s disease (HD) phenocopies’. Aims To characterize a cohort of HD phenocopies with the genetically confirmed diagnosis of McLeod syndrome. Methods This is a retrospective and prospective analysis of genotype and phenotype of sixteen McLeod cases. Results We longitudinally characterized the second largest cohort known to date. We identified novel XK mutations as well as deletions that extend into the PRRG1 gene (novel) and describe two contiguous gene deletion cases of MLS with X-linked chronic granulomatous disease (deletion also effecting the CYBB gene). This study confirms core features of MLS such as late onset hyperkinetic movements in association with neuro/myopathy, neuropsychiatric impairment, cardiac involvement, hyperCKemia. Novel aspects in this MLS series seem obstructive sleep apnea and epileptic seizure onset in childhood. Conclusions Our study expands the limited knowledge on the variable course, the various clinical manifestations and the genetic spectrum of a hereditary HD phenocopy syndrom
CRIS-Team WoS Importer:2022-04-15

NPT100-18A rescues mitochondrial oxidative stress and neuronal degeneration in human iPSC-based Parkinson's model. - Alecu, Julian; Sigutova, Veronika; Brazdis, Razvan Marius; Lörentz, Sandra; Marios-Evangelos, Bogiongko; Nursaitova, Anara; Regensburger, Martin; Roybon, Laurent; Galler, Kerstin Martina; Wrasidlo, Wolfgang; Winner, Beate; Prots, Iryna (BMC Neuroscience, 2025)
BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by protein aggregates mostly consisting of misfolded alpha-synuclein (αSyn). Progressive degeneration of midbrain dopaminergic neurons (mDANs) and nigrostriatal projections results in severe motor symptoms. While the preferential loss of mDANs has not been fully understood yet, the cell type-specific vulnerability has been linked to a unique intracellular milieu, influenced by dopamine metabolism, high demand for mitochondrial activity, and increased level of oxidative stress (OS). These factors have been shown to adversely impact αSyn aggregation. Reciprocally, αSyn aggregates, in particular oligomers, can impair mitochondrial functions and exacerbate OS. Recent drug-discovery studies have identified a series of small molecules, including NPT100-18A, which reduce αSyn oligomerization by preventing misfolding and dimerization. NPT100-18A and structurally similar compounds (such as NPT200-11/UCB0599, currently being assessed in clinical studies) point towards a promising new approach for disease-modification. METHODS: Induced pluripotent stem cell (iPSC)-derived mDANs from PD patients with a monoallelic SNCA locus duplication and unaffected controls were treated with NPT100-18A. αSyn aggregation was evaluated biochemically and reactive oxygen species (ROS) levels were assessed in living mDANs using fluorescent dyes. Adenosine triphosphate (ATP) levels were measured using a luminescence-based assay, and neuronal cell death was evaluated by immunocytochemistry. RESULTS: Compared to controls, patient-derived mDANs exhibited higher cytoplasmic and mitochondrial ROS probe levels, reduced ATP-related signals, and increased activation of caspase-3, reflecting early neuronal cell death. NPT100-18A-treatment rescued cleaved caspase-3 levels to control levels and, importantly, attenuated mitochondrial oxidative stress probe levels in a compartment-specific manner and, at higher concentrations, increased ATP signals. CONCLUSIONS: Our findings demonstrate that NPT100-18A limits neuronal degeneration in a human in vitro model of PD. In addition, we provide first mechanistic insights into how a compartment-specific antioxidant effect in mitochondria might contribute to the neuroprotective effects of NPT100-18A.
EVALuna2:586322
Keywords: iPSC; Dopaminergic neurons; Alpha-synuclein; Aggregation; Parkinson’s disease; Oxidative stress; NPT100-18A; Mitochondria; ROS

Nutrition, microbiome and multiple sclerosis : Current knowledge from basic research and clinical practice - Haghikia, A.; Linker, Ralf (Der Nervenarzt, 2018)
Epidemiological data indicate a disproportional increase in the incidence of multiple sclerosis (MS) over the last decades, particularly in industrialized countries. Although this increase is also associated with altered diagnostic criteria and improved sensitivity of imaging procedures, current data suggest that particularly alterations in our way of life play an important role. In recent years the importance of the gut and intestinal microbiome for some neurological diseases and in particular for MS was recognized. Because nutritional habits have a substantial influence on the composition of the microbiome and our nutrition has changed considerably in the last decades, nutritional components can play an important role in the pathogenesis of MS. In this further education article we summarize the currently available evidence on the role of the gut and on the effects of dietary components on the microbiome in the pathogenesis of MS.
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Objective sensor-based gait measures reflect motor impairment in multiple sclerosis patients: Reliability and clinical validation of a wearable sensor device - Felix, Flachenecker; Gaßner, Heiko; Julius, Hannik; De-Hyung, Lee; Peter, Flachenecker; Winkler, Jürgen; Eskofier, Björn; Linker, Ralf A.; Klucken, Jochen (Multiple Sclerosis and Related Disorders, 2020)
Background: Gait deficits are common in multiple sclerosis (MS) and contribute to disability but may not be easily detected in the early stages of the disease. Objectives: We investigated whether sensor-based gait analysis is able to detect gait impairments in patients with MS (PwMS). Methods: A foot-worn sensor-based gait analysis system was used in 102 PwMS and 22 healthy controls (HC) that were asked to perform the 25-foot walking test (25FWT) two times in a self-selected speed (25FWT_pref), followed by two times in a speed as fast as possible (25FWT_fast). The Multiple Sclerosis Walking Scale (MSWS-12) was used as a subjective measure of patient mobility. Patients were divided into EDSS and functional system subgroups. Results: Datasets between two consecutive measurements (test-retest-reliability) were highly correlated in all analysed mean gait parameters (e.g. 25FWT_fast: stride length r = 0.955, gait speed r = 0.969) Subgroup analysis between HC and PwMS with lower (EDSS≤3.5) and higher (EDSS 4.0–7.0) disability showed significant differences in mean stride length, gait speed, toe off angle, stance time and swing time (e.g. stride length of EDSS subgroups 25FWT_fast p ≤ 0.001, 25FWT_pref p = 0.003). The differences between EDSS subgroups were more pronounced in fast than in self-selected gait speed (e.g. stride length 25FWT_fast 33.6 cm vs. 25FWT_pref 16.3 cm). Stride length (25FWT_fast) highly correlated to EDSS (r=-0.583) and MSWS-12 (r=-0.668). We observed significant differences between HC and PwMS with (FS 0–1) and without (FS≥2) pyramidal or cerebellar disability (e.g. gait speed of FS subgroups p ≤ 0.001). Conclusion: Sensor-based gait analysis objectively supports the clinical assessment of gait abnormalities even in the lower stages of MS, especially when walking with fast speed. Stride length and gait speed where identified as the most clinically relevant gait measures. Thus, it may be used to support the assessment of PwMS with gait impairment in the future, e.g. for more objective classification of disability. Its role in home-monitoring scenarios need to be evaluated in further studies.
CRIS-Team Scopus Importer:2020-01-21
Keywords: Ambulatory sensing; EDSS; Gait analysis; Gait impairment; Mobility disability; 25 foot walk; Wearable sensors

Obstructive Sleep-Disordered Breathing Is More Common than Central in Mild Familial Dysautonomia - Hilz, Max-Josef; Möller, Sebastian; Buechner, Susanne; Czarkowska, Hanna; Ayappa, Indu; Axelrod, Felicia B.; Rapoport, David M. (Journal of Clinical Sleep Medicine, 2016)
In familial dysautonomia (FD) patients, sleep-disordered breathing (SDB) might contribute to their high risk of sleep-related sudden death. Prevalence of central versus obstructive sleep apneas is controversial but may be therapeutically relevant. We, therefore, assessed sleep structure and SDB in FD-patients with no history of SDB.11 mildly affected FD-patients (28 ± 11 years) without clinically overt SDB and 13 controls (28 ± 10 years) underwent polysomnographic recording during one night. We assessed sleep stages, obstructive and central apneas (>= 90% air flow reduction) and hypopneas (> 30% decrease in airflow with >= 4% oxygen-desaturation), and determined obstructive (oAI) and central (cAI) apnea indices and the hypopnea index (HI) as count of respective apneas/hypopneas divided by sleep time. We obtained the apnea-hypopnea index (AHI4%) from the total of apneas and hypopneas divided by sleep time. We determined differences between FD-patients and controls using the U-test and within-group differences between oAIs, cAIs, and HIs using the Friedman test and Wilcoxon test.Sleep structure was similar in FD-patients and controls. AHI4% and HI were significantly higher in patients than controls. In patients, HIs were higher than oAIs and oAIs were higher than cAIs. In controls, there was no difference between HIs, oAIs, and cAIs. Only patients had apneas and hypopneas during slow wave sleep.In our FD-patients, obstructive apneas were more common than central apneas. These findings may be related to FD-specific pathophysiology. The potential ramifications of SDB in FD-patients suggest the utility of polysomnography to unveil SDB and initiate treatment.A commentary on this article appears in this issue on page 1583.
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Occurence of Post-Traumatic Stress Symptoms, Anxiety and Depression in the Acute Phase of Transient Ischemic Attack and Stroke - Müller, Helge H.O.; Czwalinna, Katharina; Wang, Ruihao; Lücke, Caroline; Lam, Alexandra P.; Philipsen, Alexandra; Gschossmann, Jürgen M.; Moeller, Sebastian (Psychiatric Quarterly, 2021)
Rates of post-traumatic stress symptoms, anxiety and depression are increased in patients having experienced a transient ischemic attack (TIA) or stroke several months ago. However, data of psychiatric symptoms in the acute phase within the first days after ictus are lacking. In 20 patients with stroke and 33 patients with TIA we assessed disease severity by means of the NIHSS, levels of depression and anxiety by HADS, PTSD-like symptoms by PC-PTSD, quality of life (HrQoL) by SF-12, and coping style by brief COPE Inventory within the first 5 days after ictus. NIHSS on admission was lower in patients with TIA (0 ± 1) than in patients with stroke (3 ± 2, p < 0.001). HADS depression score was significantly higher in patients with stroke (7.0 ± 4.5) than in patients with TIA (4.9 ± 4.0). HADS anxiety score, HrQoL and coping styles were similar between TIA and stroke patients (p > 0.05). 5 and 3 of 33 TIA patients as well as 4 and 3 of 20 stroke patients had at least 11 points in the HADS anxiety and depression score respectively (p = 0.001). 2 of 33 TIA patients and 2 of 20 stroke patients had more than 2 points in the PC-PTSD (p = 0.646). We did not find consistent correlations between the NIHSS and the psychometric parameters. Within the first five days after patients having experienced a TIA or stroke PTSD-like, anxious and depressive symptoms are more common than in the general population. As the acute psychological status after ictus is predictive for psychiatric comorbidity years later physicians should pay attention and adequately treat psychiatric symptoms already in the acute phase of stroke. Trial Registration: German Clinical Trials Register, DRKS00021730, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021730, registered 05/19/2020- Retrospectively registered.
CRIS-Team Scopus Importer:2021-01-08
Keywords: Anxiety; Coping strategies; Depression; HRQoL; Myocardial infarction; PTSD; Stroke; TIA

Oligodendrocytes regulate the adhesion molecule ICAM-1 in neuroinflammation - Alvarado, M. N. Gonzalez; Aprato, J.; Baumeister, M.; Ekici, Arif Bülent; Kirchner, P.; Hoffmann, Alana; Winkler, Jürgen; Wegner, M.; Haase, S.; Linker, R. (Glia, 2021)
Recently, oligodendrocytes (Ol) have been attributed potential immunomodulatory effects. Yet, the exact mode of interaction with pathogenic CNS infiltrating lymphocytes remains unclear. Here, we attempt to dissect mechanisms of Ol modulation during neuroinflammation and characterize the interaction of Ol with pathogenic T cells. RNA expression analysis revealed an upregulation of immune-modulatory genes and adhesion molecules (AMs), ICAM-1 and VCAM-1, in Ol when isolated from mice undergoing experimental autoimmune encephalomyelitis (EAE). To explore whether AMs are involved in the interaction of Ol with infiltrating T cells, we performed co-culture studies on mature Ol and Th1 cells. Live cell imaging analysis showed direct interaction between both cell types. Eighty percentage of Th1 cells created contacts with Ol that lasted longer than 15 min, which may be regarded as physiologically relevant. Exposure of Ol to Th1 cells or their supernatant resulted in a significant extension of Ol processes, and upregulation of AMs as well as other immunomodulatory genes. Our observations indicate that blocking of oligodendroglial ICAM-1 can reduce the number of Th1 cells initially contacting the Ol. These results suggest that AMs may play a role in the interaction between Ol and Th1 cells. We identified Ol interacting with CD4+ cells in vivo in spinal cord tissue of EAE diseased mice indicating that our in vitro findings are of interest to further scientific research in this field. Further characterization and understanding of Ol interaction with infiltrating cells may lead to new therapeutic strategies enhancing Ol protection and remyelination potential. Oligodendrocytes regulate immune modulatory genes and adhesion molecules during autoimmune neuroinflammation Oligodendrocytes interact with Th1 cells in vitro in a physiologically relevant manner Adhesion molecules may be involved in Ol-Th1 cell interaction.
CRIS-Team WoS Importer:2021-07-16
Keywords: adhesion molecules; autoimmune neuroinflammation; EAE; oligodendrocytes; Th1 cells

Oligodendroglia and Myelin in Neurodegenerative Diseases: More Than Just Bystanders? - Ettle, Benjamin; Schlachetzki, Johannes; Winkler, Jürgen (Molecular Neurobiology, 2016)
Oligodendrocytes, the myelinating cells of the central nervous system, mediate rapid action potential conduction and provide trophic support for axonal as well as neuronal maintenance. Their progenitor cell population is widely distributed in the adult brain and represents a permanent cellular reservoir for oligodendrocyte replacement and myelin plasticity. The recognition of oligodendrocytes, their progeny, and myelin as contributing factors for the pathogenesis and the progression of neurodegenerative disease has recently evolved shaping our understanding of these disorders. In the present review, we aim to highlight studies on oligodendrocytes and their progenitors in neurodegenerative diseases. We dissect oligodendroglial biology and illustrate evolutionary aspects in regard to their importance for neuronal functionality and maintenance of neuronal circuitries. After covering recent studies on oligodendroglia in different neurodegenerative diseases mainly in view of their function as myelinating cells, we focus on the alpha-synucleinopathy multiple system atrophy, a prototypical disorder with a well-defined oligodendroglial pathology.
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Oligodendroglial α-synucleinopathy-driven neuroinflammation in multiple system atrophy - Hoffmann, Alana; Ettle, Benjamin; Battis, Kristina; Reiprich, Simone; Schlachetzki, Johannes; Masliah, Eliezer; Wegner, Michael; Kuhlmann, Tanja; Riemenschneider, Markus J.; Winkler, Jürgen (Brain Pathology, 2018)
Neuroinflammation and oligodendroglial cytoplasmic α-synuclein (α-syn) inclusions (GCIs) are important neuropathological characteristics of multiple system atrophy (MSA). GCIs are known to interfere with oligodendroglial maturation and consequently result in myelin loss. The neuroinflammatory phenotype in the context of MSA, however, remains poorly understood. Here, we demonstrate MSA-associated neuroinflammation being restricted to myeloid cells and tightly linked to oligodendroglial α-syncleinopathy. In human putaminal post-mortem tissue of MSA patients, neuroinflammation was observed in white matter regions only. This locally restricted neuroinflammation coincided with elevated numbers of α-syn inclusions, while gray matter with less α-synucleinopathy remained unaffected. In order to analyze the temporal pattern of neuroinflammation, a transgenic mouse model overexpressing human α-syn under the control of an oligodendrocyte-specific myelin basic protein (MBP) promoter (MBP29-hα-syn mice) was assessed in a pre-symptomatic and symptomatic disease stage. Strikingly, we detected an increased neuroinflammation in regions with a high α-syn load, the corpus callosum and the striatum, of MBP29-hα-syn mice, already at a pre-symptomatic stage. Furthermore, this inflammatory response was restricted to myeloid cells being highly proliferative and showing an activated, phagocytic phenotype. In contrast, severe astrogliosis was observed only in gray matter regions of MSA patients as well as MBP29-hα-syn mice. To further characterize the influence of oligodendrocytes on initiation of the myeloid immune response, we performed RNA sequencing analysis of α-syn overexpressing primary oligodendrocytes. A distinct gene expression profile including upregulation of cytokines important for myeloid cell attraction and proliferation was detected in α-syn overexpressing oligodendrocytes. Additionally, microdissected tissue of MBP29-hα-syn mice exhibited a similar cellular gene expression profile in white matter regions even pre-symptomatically. Collectively, these results imply an early crosstalk between neuroinflammation and oligodendrocytes containing α-syn inclusions leading to an immune response locally restricted to white matter regions in MSA.
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On Admission Lymphopenia in ICH Patients Is Associated with Increased Mortality and Poor Functional Outcome - Giede-Jeppe, Antje; Bobinger, Tobias; Gerner, Stefan; Lücking, Hannes; Kloska, Stephan; Kuramatsu, Joji; Schwab, Stefan; Huttner, Hagen (2016)
EVALuna2:22586

One-step Reprogramming of Human Fibroblasts into Oligodendrocyte-like Cells by SOX10, OLIG2, and NKX6.2 - Chanoumidou, Konstantina; Hernández-Rodríguez, Benjamín; Windener, Farina; Thomas, Christian; Stehling, Martin; Mozafari, Sabah; Albrecht, Stefanie; Ottoboni, Linda; Antel, Jack; Kim, Kee Pyo; Velychko, Sergiy; Cui, Qiao Ling; et al. (Stem Cell Reports, 2021)
Limited access to human oligodendrocytes impairs better understanding of oligodendrocyte pathology in myelin diseases. Here, we describe a method to robustly convert human fibroblasts directly into oligodendrocyte-like cells (dc-hiOLs), which allows evaluation of remyelination-promoting compounds and disease modeling. Ectopic expression of SOX10, OLIG2, and NKX6.2 in human fibroblasts results in rapid generation of O4+ cells, which further differentiate into MBP+ mature oligodendrocyte-like cells within 16 days. dc-hiOLs undergo chromatin remodeling to express oligodendrocyte markers, ensheath axons, and nanofibers in vitro, respond to promyelination compound treatment, and recapitulate in vitro oligodendroglial pathologies associated with Pelizaeus-Merzbacher leukodystrophy related to PLP1 mutations. Furthermore, DNA methylome analysis provides evidence that the CpG methylation pattern significantly differs between dc-hiOLs derived from fibroblasts of young and old donors, indicating the maintenance of the source cells’ “age.” In summary, dc-hiOLs represent a reproducible technology that could contribute to personalized medicine in the field of myelin diseases.
CRIS-Team Scopus Importer:2021-04-19
Keywords: ATAC-seq; compound screenin; direct conversion; epigenetic age; human fibroblasts; oligodendrocytes; PMD

Operation bei intrazerebraler Blutung? Kontra - Kuramatsu, J. B.; Huttner, Hagen (Der Nervenarzt, 2015)
EVALuna2:22378

Operative variations in temporal lobe epilepsy surgery and seizure and memory outcome in 226 patients suffering from hippocampal sclerosis - Rössler, Karl; Kasper, Burkhard; Shawarba, Julia; Walther, Katrin; Coras, Roland; Brandner, Sebastian; Winter, Fabian; Hamer, Hajo; Blümcke, Ingmar; Buchfelder, Michael (Neurological Research, 2021)
Objective: The aim of this retrospective cohort study was to assess seizure and memory outcomes following temporal lobe surgery in patients suffering from medically refractory temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). Methods: A retrospective monocentric data analysis was performed in consecutive patients who were operated on during 2002–2018. In the first decennium, standard temporal lobe resections (TLR) were predominately performed, and later, antero-temporal lobe resections (ATLR) were mainly performed. Seizure and memory outcomes over time were assessed according to ILAE/Engel classification and the Berlin Amnesia Test (BTA), respectively. Results: Altogether, 231 surgeries were performed on 226 patients (mean age, 40 years [range, 10–68 years]; male: female, 1:1.4; mean seizure duration, 25 years; and mean follow-up duration, 4.75 years [range, 1–16]). Recently, outcomes of 78.3% of the patients in the total cohort were classified as Engel class I, with 54.9% of patients being completely seizure free. The recent cohort of ATLR since 2012 showed significant more completely seizure-free patients than before 2012 (Engel IA 46.6% versus 67.7%, p < 0.0025, χ 2), although the Kaplan Meier analysis of all patients favors TLR for better seizure outcome (61% ATLR vs 73% TLR seizure free after 5 yrs, log rank p < 0.001). Verbal memory improved significantly in non-dominant patients. Minor neurological complications were noted (permanent severe complications, 0.4%; temporary severe complications, 4.8%). Conclusion: Significant improvements in seizure and memory outcomes were observed over time, with surgical technique and seizure duration as important prognostic factors. Early admittance for surgery may favor an excellent seizure outcome in patients undergoing temporal lobe resection for HS.
CRIS-Team Scopus Importer:2021-07-02
Keywords: amygdalo-hippocampectomy; antero-temporal resection; Hippocampal sclerosis; seizure outcome; standard temporal lobe resection; temporal lobe epilepsy

Optical coherence tomography in patients with a history of juvenile multiple sclerosis reveals early retinal damage - Huhn, K.; Lämmer, Robert; Oberwahrenbrock, T.; Laemmer, A.; Waschbisch, Anne; Gosar, D.; Brandt, A.; Paul, Friedemann; Linker, R. A.; Lee, D. -H. (European Journal of Neurology, 2015)
Some 3%-10% of patients with multiple sclerosis (MS) experience disease onset before the age of 18 years ('early' onset MS, EOMS). Optical coherence tomography is a non-invasive method to measure retinal nerve fibre layer thickness (RNFLT) and total macular volume (TMV) and may be useful to differentiate axonal and neuronal damage in the retina of patients with a history of EOMS. Here RNFLT and TMV in EOMS patients after a mean disease duration of 11.6 years were compared with patients with age- or disease-duration-matched later onset MS (LOMS) and healthy controls (HCs).In this observational cross-sectional study at two German academic MS centres, RNFLT and TMV were measured by spectral-domain optical coherence tomography in 32 HCs, 36 EOMS (mean age at onset 15.5 ± 2.0 years) and 58 LOMS patients.In comparison with HCs, EOMS patients displayed a significant reduction of RNFLT and TMV independently of a history of optic neuritis. In particular, RNFLT loss in EOMS was similar to that in LOMS and TMV loss was slightly higher compared with disease-duration-matched LOMS. In a generalized estimating model, the EOMS group also displayed a similar correlation between disease duration and RNFLT or TMV loss to LOMS patients.These data argue for a significant amount of axonal and neuronal damage in the retina of EOMS patients and may provide a structural basis for the observation that EOMS patients reach states of irreversible disability at a younger age than patients with LOMS.
EVALuna2:21183

Optimization on Hot-Forming Technologies - New Tool Designs and Alternative Heating Technologies for Tailored Properties - Kopp, C.; Griesbach, B.; Bader, K.-M.; Freudenberg, P.; Hezler, Christian; Russ, F. (Proceedings Tools and Forming, 2011)
LFT Import::2019-08-05 (1771)

Optimized angiographic computed tomography with intravenous contrast injection: An alternative to conventional angiography in the follow-up of clipped aneurysms? Clinical article - Gölitz, Philipp; Struffert, Tobias; Ganslandt, Oliver; Saake, Marc; Lücking, Hannes; Rösch, Julie; Knossalla, Frauke; Dörfler, Arnd (Journal of Neurosurgery, 2012)
Object. The purpose of this study was to evaluate the diagnostic accuracy of an optimized angiographic CT (ACT) program with intravenous contrast agent injection (ivACT) in the assessment of potential aneurysm remnants after neurosurgical clipping compared with conventional digital subtraction angiography (DSA). Methods. The authors report on 14 patients with 19 surgically clipped cerebral aneurysms who were scheduled to undergo angiographic follow-up. For each patient, the authors performed ivACT with dual rotational acquisition and conventional angiography including a 3D rotational run. The ivACT and 3D DSA data were reconstructed with different imaging modes, including a newly implemented subtraction mode with motion correction. Thereafter, the data sets were merged by the dual-volume technique, and freely rotatable 3D images were obtained for further analysis. Observed aneurysm remnants were electronically measured and classified for each modality by 2 experienced neuroradiologists. Results. Digital subtraction angiography and ivACT both provided high-quality images without motion artifacts. Artifact disturbances from the aneurysm clips led to a compromised, but still sufficient, image quality in 1 case. The ivACT assessed all aneurysm remnants as true-positive up to a minimal size of 2.6 x 2.4 mm in accordance with the DSA findings. There was a tendency for ivACT to overestimate the size of the aneurysm remnants. All cases without aneurysm remnants on DSA were scored correctly as true-negative by ivACT. Conclusions. By using an optimized image acquisition protocol as well as enhanced postprocessing algorithms, the noninvasive ivACT seems to achieve results comparable to those of conventional angiography in the follow-up of clipped cerebral aneurysms. The authors have shown that ivACT can provide reliable diagnostic information about potential aneurysm remnants after neurosurgical clipping with high sensitivity and specificity, sufficient for clinical decision making, at least for aneurysms in the anterior circulation located distal to the internal carotid artery. These preliminary results may be a promising step to replace conventional angiography by a noninvasive imaging technique in selected cases after aneurysm clipping.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Aneurysm clipping; Angiographic computed tomography; Follow-up imaging; Noninvasive imaging; Vascular disorders

Optimized angiographic CT using intravenous contrast injection: a noninvasive imaging option for the follow-up of coiled aneurysms? - Gölitz, Philipp; Struffert, Tobias; Kaschka, Iris; Roessler, Karl; Knossalla, F.; Dörfler, Arnd (American Journal of Neuroradiology, 2014)
Because recanalization of coiled cerebral aneurysms is reported to occur, follow-up imaging is mandatory, ideally noninvasively. Our study aimed to evaluate the accuracy of an optimized angiographic CT by using intravenous contrast material injection in the assessment of coiled cerebral aneurysms, compared with MR angiography and digital subtraction angiography, the criterion standard.We included 69 patients with 76 coiled cerebral aneurysms. In each patient, we performed an angiographic CT with intravenous contrast material injection with a dual rotational acquisition, a time-of-flight MR angiography, and a DSA. The angiographic CT with intravenous contrast material injection data was postprocessed by using newly implemented reconstructions modes and a dual-volume technique. An aneurysm occlusion rate was assessed in angiographic CT with intravenous contrast material injection and MRA; remnants were measured and correlated with DSA, respectively.Twenty-eight remnants were revealed by DSA with a mean size of 3.1 × 3.1 mm. Angiographic CT with intravenous contrast material injection demonstrated a sensitivity of 93% and a specificity of 96% in remnant detection. MRA showed almost identical accuracy (sensitivity of 93%, specificity of 100%). Assessment of remnant size by angiographic CT with intravenous contrast material injection and by MRA revealed a high significant correlation with DSA, respectively (P < .001).Optimized angiographic CT with intravenous contrast material injection and MRA demonstrated accuracy comparable with that of DSA in the follow-up of coiled aneurysms, respectively. The assessment of remnant size showed a high correlation with DSA for both techniques. Due to the lack of radiation exposure, MRA seems to be the preferred technique. However, angiographic CT with intravenous contrast material injection can be considered a reliable, noninvasive alternative in patients with MR imaging contraindications or in cases of compromising artifacts due to metal implants (ie, clips).
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Optimized Flat-Detector CT in Stroke Imaging: Ready for First-Line Use? - Eckert, Matthias; Gölitz, Philipp; Lücking, Hannes; Struffert, Tobias; Knossalla, Frauke; Dörfler, Arnd (Cerebrovascular Diseases, 2017)
Using flat-detector CT (FD-CT) for stroke imaging has the advantage that both diagnostic imaging and endovascular therapy can be performed directly within the Angio Suite without any patient transfer and time delay. Thus, stroke management could be speeded up significantly, and patient outcome might be improved. But as precondition for using FD-CT as primary imaging modality, a reliable exclusion of intracranial hemorrhage (ICH) has to be possible. This study aimed to investigate whether optimized native FD-CT, using a newly implemented reconstruction algorithm, may reliably detect ICH in stroke patients. Additionally, the potential to identify ischemic changes was evaluated.Cranial FD-CT scans were obtained in 102 patients presenting with acute ischemic stroke (n = 32), ICH (n = 45) or transient ischemic attack (n = 25). All scans were reconstructed with a newly implemented half-scan cone-beam algorithm. Two experienced neuroradiologists, unaware of clinical findings, evaluated independently the FD-CTs screening for hemorrhage or ischemic signs. The findings were correlated to CT, and rater and inter-rater agreement was assessed.FD-CT demonstrated high sensitivity (95-100%) and specificity (100%) in detecting intracerebral and intraventricular hemorrhage (IVH). Overall, interobserver agreement (? = 0.92) was almost perfect and rater agreement to CT highly significant (r = 0.81). One infratentorial ICH and 10 or 11 of 22 subarachnoid hemorrhages (SAHs) were missed of whom 7 were perimesencephalic. The sensitivity for detecting acute ischemic signs was poor in blinded readings (0 or 25%, respectively).Optimized FD-CT, using a newly implemented reconstruction algorithm, turned out as a reliable tool for detecting supratentorial ICH and IVH. However, detection of infratentorial ICH and perimesencephalic SAH is limited. The potential of FD-CT in detecting ischemic changes is poor in blinded readings. Thus, plain FD-CT seems insufficient as a standalone modality in acute stroke, but within a multimodal imaging approach primarily using the FD technology, native FD-CT seems capable to exclude reliably supratentorial hemorrhage. Currently, FD-CT imaging seems not yet ready for wide adoption, replacing regular CT, and should be reserved for selected patients. Furthermore, prospective evaluations are necessary to validate this approach in the clinical setting.
EVALuna2:22513

Oral Anticoagulants in the Oldest Old with Recent Stroke and Atrial Fibrillation - Polymeris, Alexandros A.; Macha, Kosmas; Paciaroni, Maurizio; Wilson, Duncan; Koga, Masatoshi; Cappellari, Manuel; Schaedelin, Sabine; Zietz, Annaelle; Peters, Nils; Seiffge, David J.; Haupenthal, David; Gaßmann, Luise; et al. (Annals of Neurology, 2021)
Objective To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged >= 85 years. Methods Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (<3 months) aged >= 85 versus <85 years. Primary outcome was the composite of recurrent stroke, intracranial hemorrhage (ICH) and all-cause death. We used simple, adjusted, and weighted Cox regression to account for confounders. We calculated the net benefit of DOAC versus VKA by balancing stroke reduction against the weighted ICH risk. Results In total, 5,984 of 6,267 (95.5%) patients were eligible for analysis. Of those, 1,380 (23%) were aged >= 85 years and 3,688 (62%) received a DOAC. During 6,874 patient-years follow-up, the impact of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome did not differ between patients aged >= 85 (HR >= 85y = 0.65, 95%-CI [0.52, 0.81]) and < 85 years (HR<85y = 0.79, 95%-CI [0.66, 0.95]) in simple (p(interaction) = 0.129), adjusted (p(interaction) = 0.094) or weighted (p(interaction) = 0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged >= 85 (+1.73 to +2.66) and < 85 years (+1.90 to +3.36 events/100 patient-years for ICH-weights 1.5 to 3.1). Interpretation The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old. ANN NEUROL 2021
CRIS-Team WoS Importer:2021-12-10

Oral Anticoagulation and Functional Outcome after Intracerebral Hemorrhage - Biffi, Alessandro; Kuramatsu, Joji; Leasure, Audrey; Kamel, Hooman; Kourkoulis, Christina; Schwab, Kristin; Ayres, Alison M.; Elm, Jordan; Gurol, M. Edip; Greenberg, Steven M.; Viswanathan, Anand; Anderson, Christopher D.; et al. (Annals of Neurology, 2017)
Oral anticoagulation treatment (OAT) resumption is a therapeutic dilemma in intracerebral hemorrhage (ICH) care, particularly for lobar hemorrhages related to amyloid angiopathy. We sought to determine whether OAT resumption after ICH is associated with long-term outcome, accounting for ICH location (ie, lobar vs nonlobar).We meta-analyzed individual patient data from: (1) the multicenter RETRACE study (n = 542), (2) a U.S.-based single-center ICH study (n = 261), and (3) the Ethnic/Racial Variations of Intracerebral Hemorrhage study (n = 209). We determined whether, within 1 year from ICH, OAT resumption was associated with: (1) mortality, (2) favorable functional outcome (modified Rankin Scale = 0-3), and (3) stroke incidence. We separately analyzed nonlobar and lobar ICH cases using propensity score matching and Cox regression models.We included 1,012 OAT-related ICH survivors (633 nonlobar and 379 lobar). Among nonlobar ICH survivors, 178/633 (28%) resumed OAT, whereas 86/379 (23%) lobar ICH survivors did. In multivariate analyses, OAT resumption after nonlobar ICH was associated with decreased mortality (hazard ratio [HR] = 0.25, 95% confidence interval [CI] = 0.14-0.44, p < 0.0001) and improved functional outcome (HR = 4.22, 95% CI = 2.57-6.94, p < 0.0001). OAT resumption after lobar ICH was also associated with decreased mortality (HR = 0.29, 95% CI = 0.17-0.45, p < 0.0001) and favorable functional outcome (HR = 4.08, 95% CI = 2.48-6.72, p < 0.0001). Furthermore, OAT resumption was associated with decreased all-cause stroke incidence in both lobar and nonlobar ICH (both p < 0.01).These results suggest novel evidence of an association between OAT resumption and outcome following ICH, regardless of hematoma location. These findings support conducting randomized trials to explore risks and benefits of OAT resumption after ICH. Ann Neurol 2017;82:755-765.
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Oscillations support short latency co-firing of neurons during human episodic memory formation - Roux, Frédéric; Parish, George; Chelvarajah, Ramesh; Rollings, David T.; Sawlani, Vijay; Hamer, Hajo; Gollwitzer, Stephanie; Kreiselmeyer, Gernot; Ter Wal, Marije J.; Kolibius, Luca; Staresina, Bernhard P.; Wimber, Maria; et al. (eLife, 2022)
Theta and gamma oscillations in the medial temporal lobe are suggested to play a critical role for human memory formation via establishing synchrony in neural assemblies. Arguably, such synchrony facilitates efficient information transfer between neurons and enhances synaptic plasticity, both of which benefit episodic memory formation. However, to date little evidence exists from humans that would provide direct evidence for such a specific role of theta and gamma oscillations for episodic memory formation. Here, we investigate how oscillations shape the temporal structure of neural firing during memory formation in the medial temporal lobe. We measured neural firing and local field potentials in human epilepsy patients via micro-wire electrode recordings to analyze whether brain oscillations are related to co-incidences of firing between neurons during successful and unsuccessful encoding of episodic memories. The results show that phase-coupling of neurons to faster theta and gamma oscillations correlates with co-firing at short latencies ( 20-30 ms) and occurs during successful memory formation. Phase-coupling at slower oscillations in these same frequency bands, in contrast, correlates with longer co-firing latencies and occurs during memory failure. Thus, our findings suggest that neural oscillations play a role for the synchronization of neural firing in the medial temporal lobe during the encoding of episodic memories.
CRIS-Team Scopus Importer:2022-12-23
Keywords: human; memory; neural firing; neuroscience; oscillations; single units; spikes; STDP

Osteopontin attenuates inflammation via JAK2/STAT1 pathway in hyperglycemic rats after intracerebral hemorrhage - Gong, Lei; Manaenko, Anatol; Fan, Ruiming; Huang, Lei; Enkhjargal, Budbazar; Mcbride, Devin W.; Ding, Yan; Tang, Jiping; Xiao, Xiaoqiu; Zhang, John H. (Neuropharmacology, 2018)
Acute intracerebral hemorrhage (ICH) complicated by hyperglycemia is associated with aggravation of post-stroke inflammation, leading to exacerbation of brain edema and predicting poor neurological outcomes and higher mortality of patients. Osteopontin (OPN) is a neuroprotective glycoprotein, which is able to attenuate brain injury induced by hemorrhagic stroke. In the current study we investigated whether OPN will decrease the inflammatory post-ICH response as well as attenuate brain edema and neurological deficits in hyperglycemic rats. We employed a collagenase model of ICH on male Sprague-Dawley rats (n = 148) rats and 50% of Dextrose was injected intraperitoneally (i.p) 3 h after ICH (ICH + HG). Intranasal administration of recombinant OPN (rOPN) was performed 1 h after ICH. The development of brain injury was evaluated by brain water content (BWC) and neurological deficits, western blot and immunohistochemistry study. Small interfering ribonucleic acid (siRNA) for integrin-β1 receptor and a JAK2 agonist, Coumermycin A1 (C-A1), were used for detailed investigation of the molecular pathway. The administration of OPN (3 μg) significantly improved neurobehavior and increased expression of OPN and integrin-β1 receptor in the brain followed with decrease of neutrophil infiltration, JAK2, STAT1, TNF-a, IL-1b, MMP-9 and brain edema in the ICH + HG + OPN rats compared with ICH + HG rats. The effects of OPN were reversed by the intervention of intergrin-β1 siRNA and C-A1. In conclusion, rOPN attenuated ICH-induced brain inflammation in hyperglycemic rats, leading to attenuation of brain edema and improving neurological functions. Effects of rOPN were mediated at least partly by integrin-β1 induced inhibition of JAK2/STAT1 pathway.
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Overexpression of synphilin-1 promotes clearance of soluble and misfolded alpha-synuclein without restoring the motor phenotype in aged A30P transgenic mice - Casadei, Nicolas; Pöhler, Anne-Maria; Tomas-Zapico, Cristina; Torres-Peraza, Jesus; Schwedhelm, Ivo; Witz, Annemarie; Zamolo, Irina; De Heer, Raymond; Spruijt, Berry; Noldus, Lucas P. J. J.; Klucken, Jochen; Lucas, Jose J.; et al. (Human Molecular Genetics, 2014)
Lewy bodies and neurites are the pathological hallmark of Parkinson's disease. These structures are composed of fibrillized and ubiquitinated alpha-synuclein suggesting that impaired protein clearance is an important event in aggregate formation. The A30P mutation is known for its fast oligomerization, but slow fibrillization rate. Despite its toxicity to neurons, mechanisms involved in either clearance or conversion of A30P alpha-synuclein from its soluble state into insoluble fibrils and their effects in vivo are poorly understood. Synphilin-1 is present in Lewy bodies, interacting with alpha-synuclein in vivo and in vitro and promotes its sequestration into aggresomes, which are thought to act as cytoprotective agents facilitating protein degradation. We therefore crossed animals overexpressing A30P alpha-synuclein with synphilin-1 transgenic mice to analyze its impact on aggregation, protein clearance and phenotype progression. We observed that co-expression of synphilin-1 mildly delayed the motor phenotype caused by A30P alpha-synuclein. Additionally, the presence of N- and C-terminal truncated alpha-synuclein species and fibrils were strongly reduced in double-transgenic mice when compared with single-transgenic A30P mice. Insolubility of mutant A30P and formation of aggresomes was still detectable in aged double-transgenic mice, paralleled by an increase of ubiquitinated proteins and high autophagic activity. Hence, this study supports the notion that co-expression of synphilin-1 promotes formation of autophagic-susceptible aggresomes and consecutively the degradation of human A30P alpha-synuclein. Notably, although synphilin-1 overexpression significantly reduced formation of fibrils and astrogliosis in aged animals, a similar phenotype is present in single- and double-transgenic mice suggesting additional neurotoxic processes in disease progression.
EVALuna2:25326

Oxidative stress-induced posttranslational modifications of alpha-synuclein: specific modification of alpha-synuclein by 4-hydroxy-2-nonenal increases dopaminergic toxicity - Xiang, Wei; Schlachetzki, Johannes; Helling, Stefan; Bussmann, Julia C.; Berlinghof, Marvin; Schäffer, Tilman; Marcus, Katrin; Winkler, Jürgen; Klucken, Jochen; Becker, Cord-Michael; Klucken, Jochen (Molecular and Cellular Neuroscience, 2013)
Aggregation and neurotoxicity of misfolded alpha-synuclein (?Syn) are crucial mechanisms for progressive dopaminergic neurodegeneration associated with Parkinson's disease (PD). Posttranslational modifications (PTMs) of ?Syn caused by oxidative stress, including modification by 4-hydroxy-2-nonenal (HNE-?Syn), nitration (n-?Syn), and oxidation (o-?Syn), have been implicated to promote oligomerization of ?Syn. However, it is yet unclear if these PTMs lead to different types of oligomeric intermediates. Moreover, little is known about which PTM-derived ?Syn species exerts toxicity to dopaminergic cells. In this study, we directly compared aggregation characteristics of HNE-?Syn, n-?Syn, and o-?Syn. Generally, all of them promoted ?Syn oligomerization. Particularly, HNE-?Syn and n-?Syn were more prone to forming oligomers than unmodified ?Syn. Moreover, these PTMs prevented the formation of amyloid-like fibrils, although HNE-?Syn and o-?Syn were able to generate protofibrillar structures. The cellular effects associated with distinct PTMs were studied by exposing modified ?Syn to dopaminergic Lund human mesencephalic (LUHMES) neurons. The cellular toxicity of HNE-?Syn was significantly higher than other PTM species. Furthermore, we tested the toxicity of HNE-?Syn in dopaminergic LUHMES cells and other cell types with low tyrosine hydroxylase (TH) expression, and additionally analyzed the loss of TH-immunoreactive cells in HNE-?Syn-treated LUHMES cells. We observed a selective toxicity of HNE-?Syn to neurons with higher TH expression. Further mechanistic studies showed that HNE-modification apparently increased the interaction of extracellular ?Syn with neurons. Moreover, exposure of differentiated LUHMES cells to HNE-?Syn triggered the production of intracellular reactive oxygen species, preceding neuronal cell death. Antioxidant treatment effectively protected cells from the damage triggered by HNE-?Syn. Our findings suggest a specific pathological effect of HNE-?Syn on dopaminergic neurons.
EVALuna2:4685

Pain in Fabry Disease: Practical Recommendations for Diagnosis and Treatment - Politei, Juan M.; Bouhassira, Didier; Germain, Dominique P.; Goizet, Cyril; Guerrero-Sola, Antonio; Hilz, Max-Josef; Hutton, Elspeth J.; Karaa, Amel; Liguori, Rocco; Ueceyler, Nurcan; Zeltzer, Lonnie K.; Burlina, Alessandro (Cns Neuroscience & Therapeutics, 2016)
Patients with Fabry disease (FD) characteristically develop peripheral neuropathy at an early age, with pain being a crucial symptom of underlying pathology. However, the diagnosis of pain is challenging due to the heterogeneous and nonspecific symptoms. Practical guidance on the diagnosis and management of pain in FD is needed.In 2014, experts met to discuss recent advances on this topic and update clinical guidance.Emerging disease-specific tools, including FabryScan, Fabry-specific Pediatric Health and Pain Questionnaire, and Würzburg Fabry Pain Questionnaire, and more general tools like the Total Symptom Score can aid diagnosis, characterization, and monitoring of pain in patients with FD. These tools can be complemented by more objective and quantifiable sensory testing. In male and female patients of any age, pain related to FD can be an early indication to start disease-specific enzyme replacement therapy before potentially irreversible organ damage to the kidneys, heart, or brain occurs.To improve treatment outcomes, pain should be diagnosed early in unrecognized or newly identified FD patients. Treatment should include: (a) enzyme replacement therapy controlling the progression of underlying pathology; (b) adjunctive, symptomatic pain management with analgesics for chronic neuropathic and acute nociceptive, and inflammatory or mixed pain; and (c) lifestyle modifications.
EVALuna2:22448

Pain-related evoked potentials in patients with large, mixed, and small fiber neuropathy - Siedler, Gabriela; Sommer, Claudia; Ueceyler, Nurcan (Clinical Neurophysiology, 2020)
Objective: To investigate A-delta fiber pathways in patients with large, mixed, and small fiber neuropathies using pain-related evoked potentials (PREP).
CRIS-Team WoS Importer:2020-03-10

Paradoxical kinesia in Parkinson's disease revisited: Anticipation of temporal constraints is critical - Distler, Michael; Schlachetzki, Johannes; Kohl, Zacharias; Winkler, Jürgen; Schenk, Thomas (Neuropsychologia, 2016)
Slowness of movement, called bradykinesia is the cardinal symptom of Parkinson's disease. Under distinct but not yet well-defined circumstances, patients with Parkinson's disease are able to overcome bradykinesia. One common hypothesis for this phenomenon termed paradoxical kinesia in Parkinson's disease postulates that the presentation of external sensory triggers is pivotal to elicit significant increase of motor velocity. In the present study, we examined an alternative hypothesis, namely that an internal cue in the absence of sensory cues are linked to paradoxical kinesia. To test this alternative hypothesis, patients with Parkinson's disease and healthy age-matched controls (n=9 per group) performed two movement tasks. In the stationary-object prehension task, subjects had to pick up a stationary target object. For the escaping-object task, the participants had to pick up the target object before it moved out of reach. The time available to reach for the object was adjusted individually to ensure comparable difficulty across participants. Reaction time, movement duration, and maximum velocity were assessed for both movement tasks. In Parkinson's disease patients and healthy controls, anticipation of the imminent movement of a target object significantly decreased reaction time, movement duration, and increased maximum movement velocity. The increase of maximum movement velocity in the escape-condition was significantly more pronounced for Parkinson's disease patients as compared to healthy controls. We provide evidence that internal cues such as temporal constraints are sufficient to diminish the cardinal clinical symptom of bradykinesia in Parkinson's disease. Our results suggest that expectations rather than sensory cues are critical for the emergence of paradoxical kinesia and we discuss the implications of our findings for an account of paradoxical kinesia.
EVALuna2:33521

Parametric color coding of digital subtraction angiography in the evaluation of carotid cavernous fistulas - Gölitz, Philipp; Struffert, Tobias; Lücking, Hannes; Roesch, J.; Knossalla, F.; Ganslandt, Oliver; Deuerling-Zheng, Y.; Dörfler, Arnd (Clinical Neuroradiology, 2013)
Purpose: Angiographic assessment of carotid cavernous fistulas (CCFs) can be complex. Our purpose was to examine whether the use of parametric color coding in the postprocessing of DSA series is advantageous in the evaluation of CCFs. Methods: We enrolled 16 patients with angiographically proven CCFs. Endovascular treatment was performed in 14 cases. For postprocessing of digital subtraction angiography (DSA) series, a newly implemented algorithm of parametric color coding was used, turning sequential images of two-dimensional (2D)-DSA series into a single color-coded image. Angiographic data of initial, interventional, and postinterventional 2D-DSA series were compared with color-coded images. Whether parametric color coding could facilitate evaluation of fistula architecture and provide a more precise estimation of fistula venous drainage patterns as well as whether flow analysis could reveal objective changes during and after treatment were investigated. Results: In 56 % of the cases, parametric color coding was observed to facilitate visualization of fistula angioarchitecture. Estimation of fistula drainage flow patterns was considered to be improved in 31 % of the cases. For assessment of hemodynamic changes during and after treatment, parametric color coding was assumed to be helpful in 21 % of the cases, especially because revealing flow changes that were not visible on 2D-DSA series were now visible. Conclusions: Parametric color coding is a fast application tool that might provide additional support in the angiographic evaluation of CCFs. Visualization of complex fistula architecture could be facilitated, and flow analysis might improve assessment of venous drainage patterns, thereby increasing overall diagnostic confidence. During and after treatment, hemodynamic changes that were not visible on 2D-DSA series could now be depicted. © 2012 Springer-Verlag Berlin Heidelberg.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Cerebrovascular disease; Digital subtraction angiography; Endovascular treatment; Image postprocessing

Parenchymatous hematoma in patients with atraumatic subarachnoid hemorrhage: Characteristics, treatment, and clinical outcomes - Gerner, Stefan; Hülsbrink, Robert; Reichl, Jonathan; Mrochen, Anne; Eyüpoglu, Ilker Yasin; Brandner, Sebastian; Dörfler, Arnd; Engelhorn, Tobias; Kuramatsu, Joji; Schwab, Stefan; Huttner, Hagen (International Journal of Stroke, 2020)
Background: Data regarding the influence of concomitant parenchymatous hematoma (PH) on long-term outcomes in patients with atraumatic subarachnoid hemorrhage (SAH) are scarce. Further, it is not established if these patients benefit from surgical intervention. Aim: The aim of this study was to determine the influence of concomitant PH in SAH patients on functional long-term outcome, and whether these patients may benefit from surgical hematoma evacuation. Methods: Over a 5-year period, all consecutive patients with SAH treated at the Departments of Neurology, Neuroradiology, and Neurosurgery, at the University Hospital Erlangen (Germany) were recorded. In addition to the clinical and imaging characteristics of SAH, we documented the presence, location, and volume of PH as well as treatment parameters. Outcome assessment at 12 months included functional outcome (modified Rankin scale (mRS), favorable = 0–2), health-related quality of life, and long-term complications. For outcome analysis, a propensity score matching (ratio 1:1, caliper 0.1) was performed to compare SAH patients with and without PH. Sub-analyses were performed regarding PH treatment (surgical evacuation vs. conservative). Results: A total of 494 patients with atraumatic SAH were available. Eighty-five (17.2%) had PH on initial imaging. SAH patients with PH had a worse clinical condition on admission and had a greater extent of subarachnoid/intraventricular hemorrhage. Median PH volume was 11.0 ml (5.4–31.8) with largest volumes observed in patients with ruptured middle cerebral artery (MCA)-aneurysm (31.7 ml (16.3–43.2)). After propensity-score matching (PSM), patients with PH had worse functional outcomes at 12 months (modified Rankin scale (mRS) 0–2: PH 31.8% vs. ØPH57.7% p < 0.001), and a lower rate of self-reported health compared to patients without PH (EQ-5D VAS: PH 50(30–70) vs. ØPH 80(65–95); p < 0.001). In PH patients, surgical evacuation was associated with a higher rate of favorable outcome at 12 months compared to those treated conservatively (surgery 14/28 (50.0%) vs. conservative 14/57 (24.6%); adjusted odds-ratio (OR; 95%CI): 1.34 (1.08–1.66); p = 0.001), irrespective of aneurysm location. Subgroup-analysis revealed positive associations of surgical hematoma evacuation with outcome in subgroups with larger PH volumes (>10 ml; OR (95%CI): 1.39 (1.09–1.79)), frontal PH location (OR 1.59 (1.14–2.23)), and early surgery (within 600 min after onset; OR 1.42 (1.03–1.94)). Conclusions: Concomitant PH occurs frequently in patients with SAH and is associated with functional impairment after 1 year. Surgical evacuation of PH may improve outcomes in these patients, irrespective of aneurysm-location.
CRIS-Team Scopus Importer:2020-11-27
Keywords: Cerebral hemorrhage; complications; intracerebral hemorrahage; subarachnoid hemorrhage; surgery; treatment

Parenchymatous hemorrhage is associated with unfavorable longterm outcome in patients with atraumatic subarachnoid hemorrhage - Gerner, Stefan; Kuramatsu, J.; Reichl, J.; Eyüpoglu, Ilker Yasin; Buchfelder, Michael; Dörfler, Arnd; Struffert, Tobias; Schwab, Sibylle; Huttner, Hagen (2017)
EVALuna2:34024

Parkinson’s disease as a Working Model for Global Healthcare Restructuration: The Internet of Things and Wearables Technologies - Pasluosta, Cristian Federico; Gaßner, Heiko; Winkler, Jürgen; Klucken, Jochen; Eskofier, Björn (5th EAI International Conference on Wireless Mobile Communication and Healthcare, 2015)

Parkinson's disease or multiple system atrophy: potential separation by quantitative susceptibility mapping - Marxreiter, Franz; Lambrecht, Vera; Mennecke, Angelika; Hanspach, Jannis; Jukic, Jelena; Regensburger, Martin; Herrler, Jürgen; German, Alexander; Kassubek, Jan; Groen, Georg; Mueller, Hans-Peter; Laun, Frederik Bernd; et al. (Therapeutic Advances in Neurological Disorders, 2023)
Background:Due to the absence of robust biomarkers, and the low sensitivity and specificity of routine imaging techniques, the differential diagnosis between Parkinson's disease (PD) and multiple system atrophy (MSA) is challenging. High-field magnetic resonance imaging (MRI) opened up new possibilities regarding the analysis of pathological alterations associated with neurodegenerative processes. Recently, we have shown that quantitative susceptibility mapping (QSM) enables visualization and quantification of two major histopathologic hallmarks observed in MSA: reduced myelin density and iron accumulation in the basal ganglia of a transgenic murine model of MSA. It is therefore emerging as a promising imaging modality on the differential diagnosis of Parkinsonian syndromes. Objectives:To assess QSM on high-field MRI for the differential diagnosis of PD and MSA. Methods:We assessed 23 patients (nine PDs and 14 MSAs) and nine controls using QSM on 3T and 7T MRI scanners at two academic centers. Results:We observed increased susceptibility in MSA at 3T in prototypical subcortical and brainstem regions. Susceptibility measures of putamen, pallidum, and substantia nigra reached excellent diagnostic accuracy to separate both synucleinopathies. Increase toward 100% sensitivity and specificity was achieved using 7T MRI in a subset of patients. Magnetic susceptibility correlated with age in all groups, but not with disease duration in MSA. Sensitivity and specificity were particularly high for possible MSA, and reached 100% in the putamen. Conclusion:Putaminal susceptibility measures, in particular on ultra-high-field MRI, may distinguish MSA patients from both, PD and controls, allowing an early and sensitive diagnosis of MSA.
CRIS-Team WoS Importer:2023-03-17

Partial pharmacologic blockade shows sympathetic connection between blood pressure and cerebral blood flow velocity fluctuations - Hilz, Max-Josef; Wang, Ruihao; Marthol, Harald; Liu, Mao; Tillmann, Alexandra; Riss, Stephan; Hauck, Paulina; Hoesl, Katharina M.; Wasmeier, Gerald; Stemper, Brigitte; Köhrmann, Martin (Journal of the Neurological Sciences, 2016)
Cerebral autoregulation (CA) dampens transfer of blood pressure (BP)-fluctuations onto cerebral blood flow velocity (CBFV). Thus, CBFV-oscillations precede BP-oscillations. The phase angle (PA) between sympathetically mediated low-frequency (LF: 0.03-0.15Hz) BP- and CBFV-oscillations is a measure of CA quality. To evaluate whether PA depends on sympathetic modulation, we assessed PA-changes upon sympathetic stimulation with and without pharmacologic sympathetic blockade. In 10 healthy, young men, we monitored mean BP and CBFV before and during 120-second cold pressor stimulation (CPS) of one foot (0°C ice-water). We calculated mean values, standard deviations and sympathetic LF-powers of all signals, and PAs between LF-BP- and LF-CBFV-oscillations. We repeated measurements after ingestion of the adrenoceptor-blocker carvedilol (25mg). We compared parameters before and during CPS, without and after carvedilol (analysis of variance, post-hoc t-tests, significance: p<0.05). Without carvedilol, CPS increased BP, CBFV, BP-LF- and CBFV-LF-powers, and shortened PA. Carvedilol decreased resting BP, CBFV, BP-LF- and CBFV-LF-powers, while PAs remained unchanged. During CPS, BPs, CBFVs, BP-LF- and CBFV-LF-powers were lower, while PAs were longer with than without carvedilol. With carvedilol, CPS no longer shortened resting PA. Sympathetic activation shortens PA. Partial adrenoceptor blockade abolishes this PA-shortening. Thus, PA-measurements provide a subtle marker of sympathetic influences on CA and might refine CA evaluation.
EVALuna2:22459

Pathogenic SCN2A variants cause early-stage dysfunction in patient-derived neurons - Asadollahi, Reza; Delvendahl,; Muff, R.; Tan, G.; Rodrieguez, D. G.; Turan, Sören; Russo, M.; Oneda, B.; Joset, P.; Boonsawat, P.; Masood, R.; Mocera, M.; et al. (Human Molecular Genetics, 2023)
Pathogenic heterozygous variants in SCN2A, which encodes the neuronal sodium channel Na(V)1.2, cause different types of epilepsy or intellectual disability (ID)/autism without seizures. Previous studies using mouse models or heterologous systems suggest that Na(V)1.2 channel gain-of-function typically causes epilepsy, whereas loss-of-function leads to ID/autism. How altered channel biophysics translate into patient neurons remains unknown. Here, we investigated iPSC-derived early-stage cortical neurons from ID patients harboring diverse pathogenic SCN2A variants [p.(Leu611Valfs*35); p.(Arg937Cys); p.(Trp1716*)] and compared them with neurons from an epileptic encephalopathy (EE) patient [p.(Glu1803Gly)] and controls. ID neurons consistently expressed lower Na(V)1.2 protein levels. In neurons with the frameshift variant, Na(V)1.2 mRNA and protein levels were reduced by similar to 50%, suggesting nonsense-mediated decay and haploinsufficiency. In other ID neurons, only protein levels were reduced implying Na(V)1.2 instability. Electrophysiological analysis revealed decreased sodium current density and impaired action potential (AP) firing in ID neurons, consistent with reduced Na(V)1.2 levels. In contrast, epilepsy neurons displayed no change in Na(V)1.2 levels or sodium current density, but impaired sodium channel inactivation. Single-cell transcriptomics identified dysregulation of distinct molecular pathways including inhibition of oxidative phosphorylation in neurons with SCN2A haploinsufficiency and activation of calcium signaling and neurotransmission in epilepsy neurons. Together, our patient iPSC-derived neurons reveal characteristic sodium channel dysfunction consistent with biophysical changes previously observed in heterologous systems. Additionally, our model links the channel dysfunction in ID to reduced Na(V)1.2 levels and uncovers impaired AP firing in early-stage neurons. The altered molecular pathways may reflect a homeostatic response to Na(V)1.2 dysfunction and can guide further investigations.
CRIS-Team WoS Importer:2023-05-26

Patient perspectives on the use of digital medical devices and health data for AI-driven personalised medicine in Parkinson’s Disease - Paccoud, Ivana; Valero, Mayca Marín; Marín, Laura Carrasco; Bontridder, Noémi; Ibrahim, Alzhraa; Winkler, Jürgen; Fomo, Messaline; Sapienza, Stefano; Khoury, Fouad; Corvol, Jean Christophe; Fröhlich, Holger; Klucken, Jochen (Frontiers in Neurology, 2024)
Introduction: Parkinson’s Disease (PD) affects around 8.5 million people currently with numbers expected to rise to 12 million by 2040. PD is characterized by fluctuating motor and non-motor symptoms demanding accurate monitoring. Recent advancements in digital medical devices (DMDs) like wearables and AI offer promise in addressing these needs. However, the successful implementation of DMDs in healthcare relies on patients’ willingness to adopt and engage with these digital tools. Methods: To understand patient perspectives in individuals with PD, a cross-sectional study was conducted as part of the EU-wide DIGIPD project across France, Spain, and Germany. Multidisciplinary teams including neurodegenerative clinics and patient organizations conducted surveys focusing on (i) sociodemographic information, (ii) use of DMDs (iii) acceptance of using health data (iv) preferences for the DMDs use. We used descriptive statistics to understand the use of DMDs and patient preferences and logistic regression models to identify predictors of willingness to use DMDs and to share health data through DMDs. Results: In total 333 individuals with PD participated in the study. Findings revealed a high willingness to use DMDs (90.3%) and share personal health data (97.4%,) however this differed across sociodemographic groups and was more notable among older age groups (under 65 = 17.9% vs. over 75 = 39.29%, p = 0.001) and those with higher education levels less willing to accept such use of data (university level = 78.6% vs. 21.43% with secondary level, p = 0.025). Providing instruction on the use of DMDs and receiving feedback on the results of the data collection significantly increased the willingness to use DMDs (OR = 3.57, 95% CI = 1.44–8.89) and (OR = 3.77, 95% CI = 1.01–14.12), respectively. Conclusion: The study emphasizes the importance of considering patient perspectives for the effective deployment of digital technologies, especially for older and more advanced disease-stage patients who stand to benefit the most.
CRIS-Team Scopus Importer:2025-02-04
Keywords: acceptance of digital medical devices; Adoption of AI; Parkinson’s Disease; patient preferences; patient-centeredness; personalized medicine; trust; use of health data

Patient preferences for disease-modifying drugs in multiple sclerosis therapy: a choice-based conjoint analysis - Utz, Kathrin S.; Hoog, Jana; Wentrup, Andreas; Berg, Sebastian; Laemmer, Alexandra; Jainsch, Britta; Waschbisch, Anne; Lee, De-Hyung; Linker, Ralf; Schenk, Thomas (Therapeutic Advances in Neurological Disorders, 2014)
With an increasing number of disease-modifying treatments (DMTs) for multiple sclerosis (MS), patient preferences will gain importance in the decision-making process. We assessed patients' implicit preferences for oral versus parenteral DMTs and identified factors influencing patients' treatment preference.Patients with relapsing-remitting MS (n = 156) completed a questionnaire assessing treatment preferences, whereby they had to decide between pairs of hypothetical treatment scenarios. Based on this questionnaire a choice-based conjoint analysis was conducted.Treatment frequency and route of administration showed a stronger influence on patient preference compared with frequency of mild side effects. The latter attribute was more important for treatment-naïve patients compared with DMT-experienced patients. The higher the Extended Disability Status Scale score, the more likely pills, and the less likely fewer side effects were preferred. Pills were preferred over injections by 93% of patients, when treatment frequency and frequency of side effects were held constant. However, preference switched to injections when pills had to be taken three times daily and injections only once per week. Injections were also preferred when pills were associated with frequent side effects.Our results suggest that route of administration and treatment frequency play an important role in the patients' preference for a given DMT.
EVALuna2:22318

Patient-relevant therapy goals and benefits in the treatment of epilepsy - Klein, Toni Maria; Blome, Christine; Westermayer, Vivien; Cuny, Jeanne; Hamer, Hajo (QUALITY OF LIFE RESEARCH, 2021)
CRIS-Team WoS Importer:2021-12-03

Patients’ and caregivers’ perception of multidimensional and palliative care in amyotrophic lateral sclerosis – protocol of a German multicentre study - Linse, Katharina; Weber, Constanze; Reilich, Peter; Schöberl, Florian; Boentert, Matthias; Petri, Susanne; Rödiger, Annekathrin; Posa, Andreas; Otto, Markus; Wolf, Joachim; Zeller, Daniel; Brunkhorst, Robert; et al. (Neurological Research and Practice, 2024)
Introduction: Amyotrophic lateral sclerosis (ALS) is an inevitably fatal condition that leads to a progressive loss of physical functioning, which results in a high psychosocial burden and organizational challenges related to medical care. Multidimensional and multiprofessional care is advised to meet the complex needs of patients and their families. Many healthcare systems, including Germany, may not be able to meet these needs because non-medical services such as psychological support or social counselling are not regularly included in the care of patients with ALS (pwALS). Specialised neuropalliative care is not routinely implemented nor widely available. Caregivers of pwALS are also highly burdened, but there is still a lack of support services for them. Methods: This project aims to assess the perceptions and satisfaction with ALS care in Germany in pwALS and their caregivers. This will be achieved by means of a cross-sectional, multicentre survey. The examination will assess, to which extend the patients’ needs in the six domains of physical, psychological, social, spiritual, practical and informational are being met by current care structures. This assessment will be linked to mental well-being, subjective quality of life, attitudes toward life-sustaining measures and physician-assisted suicide, and caregiver burden. The study aims to recruit 500 participants from nationwide ALS centres in order to draw comprehensive conclusions for Germany. A total of 29 centres, mostly acquired via the clinical and scientific German Network for Motor Neuron Diseases (MND-NET), will take part in the project, 25 of which have already started recruitment. Perspective: It is intended to provide data-based starting points on how current practice of care in Germany is perceived pwALS and their caregivers and how it can be improved according to their needs. Planning and initiation of the study has been completed. Trial registration: The study is registered at ClinicalTrails.gov; NCT06418646
CRIS-Team Scopus Importer:2024-07-19
Keywords: Amyotrophic lateral sclerosis; Caregiver burden; Motor neuron disease; Palliative care; Psychosocial care; Quality of care

Patients on NOACs in the Emergency Room - Gerner, Stefan; Huttner, Hagen (Current Neurology and Neuroscience Reports, 2019)
Purpose of ReviewDespite the increasing use of NOACs, there is still uncertainty on how to treat NOAC patients presenting with neurological emergencies. Initial assessment of coagulation status is challenging but essential in these patients to provide best-possible treatment in case of ischemic or hemorrhagic stroke. Meanwhile, anticoagulation reversal strategies have been suggested; yet, the optimal management is still unestablished. The current review aims to provide up-to-date information on (i) how to identify patients with NOAC intake, (ii) which therapies are feasible in the setting of ischemic and hemorrhagic stroke as well as traumatic intracranial hemorrhage, and (iii) how to proceed with patients requiring emergency lumbar puncture.Recent FindingsDespite several expert opinions, there is still an ongoing debate which NOAC patients presenting with ischemic stroke may benefit from recanalizing strategies and whether these treatment approaches can be performed safely. Results from two phase IV trials investigating the efficacy of NOAC-specific reversal agents in case of major bleeding seem promising with regard to hemostatic parameters, but these antidotes have not been verified to clinically benefit patients, and approval by authorities in parts is still pending.SummarySpecific reversal agents are on the way and will provide new treatment options in patients with NOAC-related ischemic and hemorrhagic stroke. Up to now, the decision which patients should undergo recanalizing treatment for ischemic stroke, or which specific pharmacological reversal treatment in hemorrhagic stroke should be initiated, has to be made cautiously on an individual basis after assessing hemostatic parameters.
CRIS-Team WoS Importer:2019-06-18

Patients with Multiple System Atrophy show higher variability of gait compared to Parkinson patients: impact of walking velocity - Sidoroff, V.; Raccagni, C.; Klucken, Jochen; Seppi, K.; Wenning, G. K.; Gaßner, Heiko (EUROPEAN JOURNAL OF NEUROLOGY, 2020)
CRIS-Team WoS Importer:2020-06-16

Pattern of Functional TTX-Resistant Sodium Channels Reveals a Developmental Stage of Human iPSC- and ESC-Derived Nociceptors - Eberhardt, Esther; Havlicek, Steven; Schmidt, Diana; Link, Andrea; Neacsu, Cristian; Kohl, Zacharias; Hampl, Martin; Kist, Andreas; Klinger, Alexandra; Nau, Carla; Schüttler, Jürgen; Alzheimer, Christian; et al. (Stem Cell Reports, 2015)
Human pluripotent stem cells (hPSCs) offer the opportunity to generate neuronal cells, including nociceptors. Using a chemical-based approach, we generated nociceptive sensory neurons from HUES6 embryonic stem cells and retrovirally reprogrammed induced hPSCs derived from fibroblasts. The nociceptive neurons expressed respective markers and showed tetrodotoxin-sensitive (TTXs) and -resistant (TTXr) voltage-gated sodium currents in patch-clamp experiments. In contrast to their counterparts from rodent dorsal root ganglia, TTXr currents of hPSC-derived nociceptors unexpectedly displayed a significantly more hyperpolarized voltage dependence of activation and fast inactivation. This apparent discrepancy is most likely due to a substantial expression of the developmentally important sodium channel NAV1.5. In view of the obstacles to recapitulate neuropathic pain in animal models, our data advance hPSC-derived nociceptors as a better model to study developmental and pathogenetic processes in human nociceptive neurons and to develop more specific small molecules to attenuate pain.
EVALuna2:2465

PD-L1 positive astrocytes attenuate inflammatory functions of PD-1 positive microglia in models of autoimmune neuroinflammation - Linnerbauer, Mathias; Beyer, Tobias; Nirschl, Lucy; Farrenkopf, Daniel; Lößlein, Lena; Vandrey, Oliver; Peter, Anne; Tsaktanis, Thanos; Kebir, Hania; Laplaud, David; Oellinger, Rupert; Engleitner, Thomas; et al. (Nature Communications, 2023)
Multiple Sclerosis (MS) is a chronic autoimmune inflammatory disorder of the central nervous system (CNS). Current therapies mainly target inflammatory processes during acute stages, but effective treatments for progressive MS are limited. In this context, astrocytes have gained increasing attention as they have the capacity to drive, but also suppress tissue-degeneration. Here we show that astrocytes upregulate the immunomodulatory checkpoint molecule PD-L1 during acute autoimmune CNS inflammation in response to aryl hydrocarbon receptor and interferon signaling. Using CRISPR-Cas9 genetic perturbation in combination with small-molecule and antibody-mediated inhibition of PD-L1 and PD-1 both in vivo and in vitro, we demonstrate that astrocytic PD-L1 and its interaction with microglial PD-1 is required for the attenuation of autoimmune CNS inflammation in acute and progressive stages in a mouse model of MS. Our findings suggest the glial PD-L1/PD-1 axis as a potential therapeutic target for both acute and progressive MS stages.
CRIS-Team Scopus Importer:2023-09-22

Peak Edema Extension Distance: An Edema Measure Independent from Hematoma Volume Associated with Functional Outcome in Intracerebral Hemorrhage - Giede-Jeppe, Antje; Gerner, Stefan T.; Sembill, Jochen; Kuramatsu, Joji; Lang, Stefan; Lücking, Hannes; Staykov, Dimitre; Huttner, Hagen B.; Volbers, Bastian (Neurocritical Care, 2023)
Background: Our objective was to test the association between hematoma volume and long-term (> 72 h) edema extension distance (EED) evolution and the association between peak EED and early EED increase with functional outcome at 3 months in patients with intracerebral hemorrhage (ICH). Methods: This retrospective cohort study included patients with spontaneous supratentorial ICH between January 2006 and January 2014. EED, an edema measure defined as the distance between the hematoma border and the outer edema border, was calculated by using absolute hematoma and edema volumes. We used multivariable logistic regression accounting for age, ICH volume, and location and receiver operating characteristic analysis for assessing measures associated with functional outcome and EED evolution. Functional outcome after 3 months was assessed by using the modified Rankin Scale (0–3 = favorable, 4–6 = unfavorable). To identify properties associated with peak EED multivariable linear and logistic regression analyses were conducted. Results: A total of 292 patients were included. Median age was 70 years (interquartile range [IQR] 62–78), median ICH volume on admission 17.7 mL (IQR 7.9–40.2), median peak perihemorrhagic edema (PHE) volume was 37.5 mL (IQR 19.1–60.6), median peak EED was 0.67 cm (IQR 0.51–0.84) with an early EED increase up to 72 h (EED72–0) of 0.06 cm (− 0.02 to 0.15). Peak EED was found to be independent of ICH volume (R 2 = 0.001, p = 0.6). In multivariable analyses, peak EED (odds ratio 0.224, 95% confidence interval [CI] [0.071–0.705]) and peak PHE volume (odds ratio 0.984 [95% CI 0.973–0.994]) were inversely associated with favorable functional outcome at 3 months. Receiver operating characteristic analysis identified a peak PHE volume of 26.8 mL (area under the curve 0.695 [95% CI 0.632–0.759]; p ≤ 0.001) and a peak EED of 0.58 cm (area under the curve 0.608 [95% CI 0.540–0.676]; p = 0.002) as best predictive values for outcome discrimination. Conclusions: Compared with absolute peak PHE volume, peak EED represents a promising edema measure in patients with ICH that is largely hematoma volume-independent and nevertheless associated with functional outcome.
CRIS-Team Scopus Importer:2023-12-08
Keywords: Early EED increase; Edema; EED; ICH; PHE

Peak perihemorrhagic edema correlates with functional outcome in intracerebral hemorrhage - Volbers, Bastian; Giede-Jeppe, Antje; Gerner, Stefan; Sembill, Jochen; Kuramatsu, Joji; Lang, Stefan; Lücking, Hannes; Staykov, Dimitre; Huttner, Hagen (Neurology, 2018)
Objective To evaluate the association of perihemorrhagic edema (PHE) evolution and peak edema extent with day 90 functional outcome in patients with intracerebral hemorrhage (ICH) and identify pathophysiologic factors influencing edema evolution. Methods This retrospective cohort study included patients with spontaneous supratentorial ICH between January 2006 and January 2014. ICH and PHE volumes were studied using a validated semiautomatic volumetric algorithm. Multivariable logistic regression and propensity score matching (PSM) accounting for age, ICH volume, and location were used for assessing measures associated with functional outcome and PHE evolution. Clinical outcome on day 90 was assessed using the modified Rankin Scale (0-3 = favorable, 4-6 = poor). Results A total of 292 patients were included. Median age was 70 years (interquartile range [IQR] 62-78), median ICH volume on admission 17.7 mL (IQR 7.9-40.2). Besides established factors for functional outcome, i.e., ICH volume and location, age, intraventricular hemorrhage, and NIH Stroke Scale score on admission, multivariable logistic regression revealed peak PHE volume (odds ratio [OR] 0.984 [95% confidence interval (CI) 0.973-0.994]) as an independent predictor of day 90 outcome. Peak PHE volume was independently associated with initial PHE increase up to day 3 (OR 1.060 [95% CI 1.018-1.103]) and neutrophil to lymphocyte ratio on day 6 (OR 1.236 [95% CI 1.034-1.477; PSM cohort, n = 124]). Initial PHE increase (PSM cohort, n = 224) was independently related to hematoma expansion (OR 3.647 [95% CI 1.533-8.679]) and fever burden on days 2-3 (OR 1.456 [95% CI 1.103-1.920]). Conclusion Our findings suggest that peak PHE volume represents an independent predictor of functional outcome after ICH. Inflammatory processes and hematoma expansion seem to be involved in PHE evolution and may represent important treatment targets.
EVALuna2:34919

Peak Troponin I Levels Are Associated with Functional Outcome in Intracerebral Hemorrhage - Gerner, Stefan; Auerbeck, Katrin; Sprügel, Maximilian; Sembill, Jochen; Madzar, Dominik; Gölitz, Philipp; Kuramatsu, Joji; Schwab, Stefan; Huttner, Hagen; Hölter, Philip (Cerebrovascular Diseases, 2018)
Background: Troponin I is a widely used and reliable marker of myocardial damage and its levels are routinely measured in acute stroke care. So far, the influence of troponin I elevations during hospital stay on functional outcome in patients with atraumatic intracerebral hemorrhage (ICH) is unknown. Methods: Observational single-center study including conservatively treated ICH patients over a 9-year period. Patients were categorized according to peak troponin I level during hospital stay (<= 0.040, 0.041-0.500, > 0.500 ng/mL) and compared regarding baseline and hematoma characteristics. Multivariable analyses were performed to investigate independent associations of troponin levels during hospital stay with functional outcome -assessed using the modified Rankin Scale (mRS; favorable 0-3/unfavorable 4-6) -and mortality after 3 and 12 months. To account for possible con-founding propensity score (PS)-matching (1: 1; caliper 0.1) was performed accounting for imbalances in baseline characteristics to investigate the impact of troponin I values on outcome. Results: Troponin elevations (> 0.040 ng/mL) during hospital stay were observed in 308 out of 745 (41.3%) patients and associated with poorer status on admission (Glasgow Coma Scale/National Institute of Health Stroke Scale). Multivariable analysis revealed troponin I levels during hospital stay to be independently associated with unfavorable outcome after 12 months (risk ratio [95% CI]: 1.030 [1.009-1.051] per increment of 1.0 ng/mL; p = 0.005), but not with mortality. After PS-matching, patients with troponin I elevation (= 0.040 ng/mL) versus those without had a significant higher rate of -unfavorable outcome after 3 and 12 months (mRS 4-6 at 3 months: < 0.04 ng/mL: 159/265 [60.0%] versus = 0.04 ng/mL: 199/266 [74.8%]; p < 0.001; at 12 months: < 0.04 ng/mL: 141/248 [56.9%] versus <= 0.04 ng/mL: 179/251 [71.3%]; p = 0.001). Conclusions: Troponin I elevations during hospital stay occur frequently in ICH patients and are independently associated with functional outcome after 3 and 12 months but not with mortality. (c) 2018 S. Karger AG, Basel
EVALuna2:34936

Pearls & Oy-sters: Moyamoya Vasculopathy and Its Association With Congenital Heart Disease - Osterloh, Justus; Heim, Christian; Siedler, Gabriela; Engelhorn, Tobias; Dörfler, Arnd; Schwab, Stefan; Kallmünzer, Bernd (Neurology, 2021)
CRIS-Team Scopus Importer:2021-06-25

Pearls & Oy-sters: SARS-CoV-2 Infection of the CNS in a Patient With Meningeosis Carcinomatosa - Steininger, Philipp; Seifert, Frank; Balk, Stefanie; Kuramatsu, Joji; Kremer, Andreas; Coras, Roland; Engelhorn, Tobias; Maier, Clara; Tenbusch, Matthias; Korn, Klaus; Enßer, Armin (Neurology, 2021)
CRIS-Team Scopus Importer:2021-03-26

Performance of different osteosynthesis materials in microvascular fibula free flap reconstruction - Nobis, Christopher-Philipp; Lutz, Rainer; Weber, Margarete; Preidl, Raimund; Goetze, Elisabeth; Frohwitter, Gesche; Kesting, Marco Rainer (British Journal of Oral and Maxillofacial Surgery, 2022)
Purpose: Fibula free flap (FFF) is the main reconstructive choice for large mandibular defects. Recent improvements were made regarding planning and surgical procedure, but choice of osteosynthesis material (OSM) for segment-fixation remains controversial. Materials and methods: A retrospective cohort study obtained clinical and radiological data from FFF-patients. Data was screened for OSM, surgical procedure and complications as OSM fractures, loosening, exposure, or insufficient osseous consolidation. Results: 80 patients with FFF were included. Planning was CAD/CAM (n=29), Recon Guide (n=26) or without planning (n=25). OSM was 2.0mm-miniplates in standard (n=26), preformed (n=6), CAD/CAM (n=14) or ReconGuide (n=23) variation and 2.3mm-reconstruction-plates in standard (n=5) or CAD/CAM (n=6) variation. Complications were observed in 21 cases, fractures in 10 times overall, but with low rates for preformed (n=1), ReconGuide (n=3) and none for CAD/CAM. Analysis detected significant correlations between used OSM and plate exposure (p = .000), but none regarding fracture (p = .275), loosening (p = .714) or insufficient osseous consolidation (p = .208). No correlations were observed between complications and OSM (p = .609) or diagnosis (p = .716). Conclusion: Fixation of FFF segments for reconstruction is possible with various OSM providing good clinical outcome. No significant differences were detected regarding prevention of complications by any osteosynthesis material (miniplate vs. macroplate). Although no differences were detected, miniplate usage is advocated whenever clinically reasonable, due to more facile reintervention possibilities and reduced implanted foreign material. Nevertheless, decision for ideal OSM must remain patient-specific and cannot be generalized.
CRIS-Team Scopus Importer:2022-04-08
Keywords: CAD/CAM; complications; fibula free flap; miniplate; osteosynthesis; ReconGuide

Perihemorrhagic edema revisiting hematoma volume, location and surface - Sprügel, Maximilian; Kuramatsu, J. B.; Volbers, Bastian; Koelbl, K.; Gerner, Stefan; Lücking, Hannes; Dörfler, Arnd; Schwab, Stefan; Huttner, Hagen; Hölter, Philip (JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2019)
CRIS-Team WoS Importer:2019-07-19

Perihemorrhagic edema: Revisiting hematoma volume, location, and surface - Sprügel, Maximilian; Kuramatsu, Joji; Volbers, Bastian; Gerner, Stefan; Sembill, Jochen; Madžar, Dominik; Bobinger, Tobias; Kölbl, Kathrin; Lücking, Hannes; Dörfler, Arnd; Schwab, Stefan; Huttner, Hagen; et al. (Neurology, 2019)
OBJECTIVE: To determine the influence of intracerebral hemorrhage (ICH) location and volume and hematoma surface on perihemorrhagic edema evolution. METHODS: Patients with ICH of the prospective Universitätsklinikum Erlangen Cohort of Patients With Spontaneous Intracerebral Hemorrhage (UKER-ICH) cohort study (NCT03183167) between 2010 and 2013 were analyzed. Hematoma and edema volume during hospital stay were volumetrically assessed, and time course of edema evolution and peak edema correlated to hematoma volume, location, and surface to verify the strength of the parameters on edema evolution. RESULTS: Overall, 300 patients with supratentorial ICH were analyzed. Peak edema showed a high correlation with hematoma surface (R2 = 0.864, p < 0.001) rather than with hematoma volumes, regardless of hematoma location. Smaller hematomas with a higher ratio of hematoma surface to volume showed exponentially higher relative edema (R2 = 0.755, p < 0.001). Multivariable logistic regression analysis revealed a cutoff ICH volume of 30 mL, beyond which an increase of total mass lesion volume (combined volume of hematoma and edema) was not associated with worse functional outcome. Specifically, peak edema was associated with worse functional outcome in ICH <30 mL (odds ratio [OR] 2.63, 95% confidence interval [CI] 1.68-4.12, p < 0.001), contrary to ICH ≥30 mL (OR 1.20, 95% CI 0.88-1.63, p = 0.247). There were no significant differences between patients with lobar and those with deep ICH after adjustment for hematoma volumes. CONCLUSIONS: Peak perihemorrhagic edema, although influencing mortality, is not associated with worse functional outcomes in ICH volumes >30 mL. Although hematoma volume correlates with peak edema extent, hematoma surface is the major parameter for edema evolution. The effect of edema on functional outcome is therefore more pronounced in smaller and irregularly shaped hematomas, and these patients may particularly benefit from edema-modifying therapies.
CRIS-Team Scopus Importer:2019-09-27

Perioperative changes in cortical excitability, mood, and quality of life in patients with primary hyperparathyroidism: a pilot study using transcranial magnetic stimulation - Hermsen, A.; Eienbröker, A.; Haag, A.; Mylius, V.; Hamer, Hajo; Menzler, K.; Karakas, E.; Rosenow, F. (European Journal of Endocrinology, 2014)
Serum calcium (Ca(2)(+)) and parathyroid hormone (PTH), amongst others, modify cortical excitability. Alterations in cortical excitability were shown in patients with epilepsy as well as hyper- or hypoparathyroidism. In patients with primary hyperparathyroidism (pHPT), preoperative elevated serum calcium and parathyroidectomy (PTx) may affect mood and quality of life. We hypothesized that perioperative changes in Ca(2)(+) and PTH in pHPT will affect cortical excitability and improve subjective health.Transcranial magnetic stimulation (TMS) was performed before and after surgery in 15 pHPT patients. We measured resting motor threshold, cortical silent period (CSP), short intracortical inhibition, and intracortical facilitation. Health questionnaires were administered before, 1 day and 6 months after PTx, along with the disease-specific Pasieka's parathyroid assessment of symptoms (PAS), which was, to our knowledge, its first use in German.SURGERY WAS SUCCESSFUL IN ALL PATIENTS. TMS-MEASUREMENTS REMAINED UNCHANGED WHEN ANALYZING ALL PATIENTS IN THIS PILOT STUDY. POSTOPERATIVELY, DEPRESSION DECLINED (P=0.05) AND QUALITY OF LIFE IMPROVED SIGNIFICANTLY (P=0.001) IN THE SF-36-SUBSCALES: vitality, social functioning, mental health and subjective health transition (post-hoc analysis). The PAS proved early relief of disease-specific symptoms (P<0.001).We found unchanged cortical excitability comparing pre- and post-PTx in this pilot study. Mood and quality of life improved postoperatively. The German PAS is valuable in detecting disease-specific changes early after PTx.
EVALuna2:22381

Peripheral CD19+ B-cell counts and infusion intervals as a surrogate for long-term B-cell depleting therapy in multiple sclerosis and neuromyelitis optica/neuromyelitis optica spectrum disorders - Ellrichmann, Gisa; Bolz, Jan; Peschke, Maren; Duscha, Alexander; Hellwig, Kerstin; Lee, De-Hyung; Linker, Ralf; Gold, Ralf; Haghikia, Aiden (Journal of Neurology, 2019)
BACKGROUND: With ocrelizumab another drug is available for the treatment of multiple sclerosis (MS). Little is known on the long-term use of ocrelizumab on immune cell subsets, and no surrogate markers are available. Rituximab (RTX) has been in off-label use for the treatment of MS, neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD) for > 10 years. OBJECTIVE: We evaluated the long-term depletion and repopulation rate of peripheral CD19+ B-cells as a potential surrogate for the clinical outcome, and whether it may serve for dosage and time-to-infusion decision making. METHODS: We evaluated the CD19+ and CD4+/8+ T-cell counts in n = 153 patients treated with RTX (132 MS, 21 NMO/NMOSD). The dosages ranged from 250 to 2000 mg RTX. Depletion/repopulation rates of CD19+ B-cells as well as long-term total lymphocyte cell counts, were assessed and corroborated with EDSS, ARR (annualized relapse rate), MRI, and time to reinfusion. RESULTS: CD19+ B-cells' repopulation rate significantly varied depending on the dosage applied leading to individualized application intervals (mean 9.73 ± 0.528 months). Low/absent CD19+ B-cell counts were associated with reduced ARR, EDSS, and GD+-MRI-lesions. Long-term B-cell-depleting therapy led to a transiently skewed CD4+/8+ T-cell ratio due to reduced CD4+ T-cells and absolute lymphocyte counts, which recovered after the second cycle. CONCLUSION: Our data suggest that CD19+ B-cell repopulation latency may serve as surrogate marker for individualized treatment strategies in MS and NMO/NMOSD, which proved clinically equally effective in our cohort as evaluated by previous studies.
EVALuna2:36322

Peripheral pulse measurement after ischemic stroke: A feasibility study - Kallmünzer, Bernd; Bobinger, Tobias; Kahl, Nicolas; Kopp, Markus; Kurka, Natalia; Hilz, Max-Josef; Marquardt, Lars; Schwab, Stefan; Köhrmann, Martin (Neurology, 2014)
To investigate feasibility and diagnostic accuracy of measurement of the peripheral pulse (MPP) at the radial artery as a simple, noninvasive screening tool for paroxysmal atrial fibrillation (pAF) in patients after acute ischemic stroke.Two hundred fifty-six patients with acute ischemic stroke and the patients' relatives at a tertiary stroke center were prospectively included. Participants were instructed for characteristics of atrial fibrillation (AF) in MPP using standardized educational material. Measurements of participants as well as a health care professional were then compared with simultaneous blinded ECG to evaluate diagnostic accuracy parameters.MPP by the health care professional or patients' relatives had a diagnostic sensitivity of 96.5% and 76.5%, respectively, with 94.0% and 92.9% specificity for the detection of AF. Self-measurements were reliably performed by 89.1% of competent patients with a diagnostic sensitivity of 54.1% and 96.2% specificity. False-positive results were limited to 6 cases (2.7%) with a positive predictive value of 76.9% and a negative predictive value of 90.0%.With a low rate of false-positive results, MPP offers an easy, ubiquitously available, noninvasive, first-step screening tool to guide ECG diagnostics for pAF after ischemic stroke. The data warrant a prospective trial evaluating the efficacy of MPP-guided ECG diagnostics in secondary prevention after stroke, which is now underway.This study provides Class I evidence that MPP by patients or relatives accurately distinguishes AF from normal heart rhythm as compared with continuous ECG.
EVALuna2:22299

PERIPHERAL PULSE MEASUREMENTS FOR THE DETECTION OF SILENT ATRIAL FIBRILLATION: RESULTS FROM THE PROSPECTIVE, CONTROLLED TRIAL "KNOW YOUR PULSE POST STROKE" - Kallmünzer, Bernd; Macha, Kosmas; Wang, Ruihao; Siedler, Gabriela; Stoll, Svenja; Marsch, Armin; Gerner, Stefan; Winder, Klemens; Koehn, J.; Schwab, Stefan; Koehrmann, M. (INTERNATIONAL JOURNAL OF STROKE, 2020)
CRIS-Team WoS Importer:2021-01-22

Persistence with antiepileptic drugs in epilepsy patients treated in neurological practices in Germany - Jacob, Louis; Hamer, Hajo; Kostev, Karel (Epilepsy and Behavior, 2017)
The goal of this study was to analyze the persistence with antiepileptic drugs (AED) and associated factors in patients followed in neurological practices in Germany.This study included patients aged 18years or over who received two initial diagnoses of epilepsy and a first prescription of AED between 2007 and 2015 in a neurological practice (index date). The main outcome measure was the rate of AED persistence within five years of the index date. Kaplan-Meier analyses were performed to study treatment persistence as a function of age. A Cox proportional hazards regression model was used to estimate the relationship between non-persistence and demographic/clinical variables.A total of 8192 patients followed in neurological practices were included. After five years of follow-up, 41.1% (<=40years), 45.2%, (41-60years) and 50.1% (>60years) of patients followed in neurological practices were persistent (log-rank p-value<0.001). A negative association was found between discontinuation and age (<=40years vs. >60years: OR=1.19, 95% CI: 1.09-1.31; 41-60years vs. >60years: OR=1.10, 95% CI: 1.01-1.19). Furthermore, patients receiving old AED (OR=1.16, 95% CI: 1.01-1.34) or gabapentin (OR=1.46, 95% CI: 1.16-1.83) and those diagnosed with depression (OR=1.12, 95% CI: 1.03-1.21) were at a higher risk of non-persistence, whereas those receiving levetiracetam (OR=0.69, 95% CI: 0.60-0.80) or lamotrigine (OR=0.88, 95% CI: 0.79-0.97) and those with dementia (OR=0.74, 95% CI: 0.65-0.83) were at a lower risk.The rate of epilepsy patients persistent with AED was low after five years of treatment. Age, gender, co-morbidities, and drug characteristics were associated with this persistence.
EVALuna2:22554

Perturbation during treadmill training improves dynamic balance and gait in Parkinson’s disease: A single-blind randomized controlled pilot trial - Steib, Simon; Klamroth, Sarah; Gaßner, Heiko; Pasluosta, Cristian Federico; Eskofier, Björn; Winkler, Jürgen; Klucken, Jochen; Pfeifer, Klaus (Neurorehabilitation and Neural Repair, 2017)

Perturbation Treadmill Training Improves Clinical Characteristics of Gait and Balance in Parkinson's Disease - Gaßner, Heiko; Steib, Simon; Klamroth, Sarah; Pasluosta, Cristian Federico; Adler, Werner; Eskofier, Björn; Pfeifer, Klaus; Winkler, Jürgen; Klucken, Jochen (Journal of Parkinson's Disease, 2019)
Background: Impaired gait and postural stability are cardinal motor symptoms in Parkinson's disease (PD). Treadmill training improves gait characteristics in PD. Objective: This study investigates if postural perturbations during treadmill training improve motor performance and particularly gait and postural stability in PD. Methods: This work presents secondary outcome measures of a pilot randomized controlled trial. PD patients (n=43) recruited at the University Hospital Erlangen were randomly allocated to the experimental (perturbation treadmill training, PTT, n=21) or control group (conventional treadmill training, CTT, n=22). Outcome measures were collected at baseline, after 8 weeks of intervention, and 3 months follow-up. Motor impairment was assessed by the Unified Parkinson Disease Rating Scale part-III (UPDRS-III), Postural Instability and Gait Difficulty score (PIGD), and subitems 'Gait' and 'Postural stability' by an observer blinded to the randomization. Intervention effects were additionally compared to progression rates of a matched PD cohort (n=20) receiving best medical treatment (BMT). Results: Treadmill training significantly improved UPDRS-III motor symptoms in both groups with larger effect sizes for PTT (-38%) compared to CTT (-20%). In the PTT group solely, PIGD -34%, and items 'Gait' -50%, and 'Postural stability' -40% improved significantly in comparison to CTT (PIGD -24%, 'Gait' -22%, 'Postural stability' -33%). Positive effects persisted in PTT after 3 months and appeared to be beneficial compared to BMT. Conclusions: Eight weeks of PTT showed superior improvements of motor symptoms, particularly gait and postural stability. Sustainable effects indicate that PTT may be an additive therapy option for gait and balance deficits in PD.
CRIS-Team Scopus Importer:2019-06-18
Keywords: Gait analysis; Parkinson's disease; postural stability; treadmill training

Perturbation Treadmill Training – Introducing Postural Challenge and Practice Variability in Gait Rehabilitation of Parkinson’s Patients - Steib, Simon; Klamroth, Sarah; Gaßner, Heiko; Goßler, Julia; Winkler, Jürgen; Eskofier, Björn; Klucken, Jochen; Pfeifer, Klaus (Human Movement and Technology, 2016)

Phase-amplitude coupling measures for determination of the epileptic network: A methodological comparison - Ali, Ryshum; Gollwitzer, Stephanie; Reindl, Caroline; Hamer, Hajo; Coras, Roland; Blümcke, Ingmar; Buchfelder, Michael; Hastreiter, Peter; Rampp, Stefan (Journal of Neuroscience Methods, 2022)
CRIS-Team WoS Importer:2022-05-13
Keywords: EEG; Epilepsy; Phase-Amplitude Coupling

Phenobarbital in super-refractory status epilepticus (PIRATE): A retrospective, multicenter analysis - Kunst, Stefan; Rojo, Mikel L.; Schmidbauer, Moritz O.; Pelz, Johann; Mueller, Annekatrin; Minnerup, Jens; Meyer, Lennart; Madžar, Dominik; Reindl, Caroline; Madlener, Marie; Malter, Michael; Neumann, Bernhard; et al. (Epilepsia, 2023)
Objective: Super-refractory status epilepticus (SRSE) is an enduring or recurring SE after 24 h or more of general anesthesia. This study aimed to evaluate the efficacy and safety of phenobarbital (PB) for the treatment of SRSE.
CRIS-Team WoS Importer:2023-05-12

Physical Activity in Multiple Sclerosis: A Comparative Study of Vitamin D, BDNF and Regulatory T Cell Populations - Waschbisch, Anne; Wenny, Ingrid; Tallner, Alexander; Schwab, Stefan; Pfeifer, Klaus; Mäurer, Mathias (European neurology, 2012)

Physical and mental health comorbidities of patients with epilepsy in Germany – A retrospective cohort study - Uepping, Peter; Hamer, Hajo; Scholten, Jerome; Kostev, Karel (Epilepsy & Behavior, 2021)
Aims: The aim of this study was to estimate the prevalence of physical and psychological comorbidities in patients with epilepsy in Germany in order to better understand the complex clinical picture and its consequences. Methods: This retrospective cohort study included adult individuals with a diagnosis of epilepsy between January 2018 and December 2018 (index date). Patients with epilepsy were matched 1:1 with patients without epilepsy by age, sex, and physician. The study outcomes included the associations between epilepsy and different physical and mental disorders documented within 365 days after the index date as well as multimorbidity defined as at least two, three, four, and five different diagnoses. The present study used multivariate logistic regression models with all study disorders as dependent variables and epilepsy as an impact variable. Results: After 1:1 matching, the present study included 7942 patients with and 7942 patients without epilepsy (mean age: 58.0 years; 49.7% female). Epilepsy was significantly positively associated with nine disorders, and the strongest associations were with mental retardation (Odds Ratio (OR): 21.11 (95% Confidence Intervals (CI): 12.52–35.59)), cerebrovascular diseases (OR: 3.14 (95% CI: 2.80–3.55)), and dementia (OR: 1.72 (95% CI: 1.47–2.01)). Epilepsy was associated with significantly increased odds of multimorbidity. Conclusion: In summary, individuals with epilepsy have an increased prevalence of comorbidities that increase with age. Further research should be undertaken in this area, including the etiology of comorbidities.
CRIS-Team Scopus Importer:2021-03-05
Keywords: Cohort study; Comorbidity; Epilepsy; Multimorbidity

Physics-Informed Conditional Autoencoder Approach for Robust Metabolic CEST MRI at 7T - Rajput, Junaid R.; Möhle, Tim A.; Fabian, Moritz; Mennecke, Angelika; Sembill, Jochen; Kuramatsu, Joji; Schmidt, Manuel; Dörfler, Arnd; Maier, Andreas; Zaiß, Moritz (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), 2023)
Chemical exchange saturation transfer (CEST) is an MRI method that provides insights on the metabolic level. Several metabolite effects appear in the CEST spectrum. These effects are isolated by Lorentzian curve fitting. The separation of CEST effects suffers from the inhomogeneity of the saturation field B1. This leads to inhomogeneities in the associated metabolic maps. Current B1 correction methods require at least two sets of CEST-spectra. This at least doubles the acquisition time. In this study, we investigated the use of an unsupervised physics-informed conditional autoencoder (PICAE) to efficiently correct B1 inhomogeneity and isolate metabolic maps while using a single CEST scan. The proposed approach integrates conventional Lorentzian model into the conditional autoencoder and performs voxel-wise B1 correction and Lorentzian line fitting. The method provides clear interpretation of each step and is inherently generative. Thus, CEST-spectra and fitted metabolic maps can be created at arbitrary B1 levels. This is important because the B1 dispersion contains information about the exchange rates and concentration of metabolite protons, paving the way for their quantification. The isolated maps for tumor data showed a robust B1 correction and more than 25% increase in structural similarity index (SSIM) with gadolinium reference image compared to the standard interpolation-based method and subsequent Lorentzian curve fitting. This efficient correction method directly results in at least 50% reduction in scan time.
CRIS-Team Scopus Importer:2023-11-03
Keywords: Acquisition time; Bound loss; CEST; Interpretability; Lorentzian fit; Physics-informed autoencoder

Physiological effects of cigarette smoking in the limbic system revealed by 3 tesla magnetic resonance spectroscopy - Mennecke, Angelika; Gossler, Andrea; Hammen, Thilo; Dörfler, Arnd; Stadlbauer, Andreas; Roesch, Julie; Kornhuber, Johannes; Bleich, Stefan; Dölken, Marc; Thürauf, Norbert (Journal of Neural Transmission, 2014)
Several studies and recent models of effects of nicotine, the main addictive and psychoactive component in tobacco, point to action of the drug on the limbic system during maintenance of addiction, either direct or indirect via projections from the ventral tegmental area. The objective of this study was to demonstrate physiological effects of cigarette smoking on the hippocampus and the grey matter of the dorsal anterior cingulate cortex in the human brain with regard to addiction and withdrawal. This aim was achieved by group comparisons of results of magnetic resonance spectroscopy between non-smokers, smokers and smokers during withdrawal. 12 smokers and 12 non-smokers were measured with single voxel proton magnetic resonance spectroscopy for total N-acetyl aspartate, glutamate and glutamine, choline-containing compounds, myo-inositol and total creatine in the right and the left hippocampus and in the right and the left dorsal anterior cingulate cortex. Smokers were examined twice, first during regular cigarette smoking and second on the third day of nicotine withdrawal. The ratios to total creatine were used for better reliability. In our study, Glx/tCr was significantly increased and tCho/tCr was significantly decreased in the left cingulate cortex in smokers compared to non-smokers (p = 0.01, both). Six out of seven smokers showed normalization of the Glx/tCr in the left cingulate cortex during withdrawal. Although these results are preliminary due to the small sample size, our results confirm the assumption that cigarette smoking interferes directly or indirectly with the glutamate circuit in the dorsal anterior cingulate cortex.
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Physiology and pathophysiology of female sexual function - Hilz, Max-Josef; Wang, Ruihao (Elsevier, 2022)
Female sexual dysfunction (FSD) affects many million women. The FSD prevalence can be as high as 43% among women younger than 60 years. Classifications include disorders of desire, arousal, orgasm, and pain. Revised DSM-5 definitions include female sexual interest/arousal disorder (FSIAD), genitopelvic pain/penetration disorder (GPPD), and female orgasmic disorder (FOD). Sexual function requires interaction of multiple levels and areas of the central and peripheral somatic and autonomic nervous system. Among central areas involved in arousal and sexual responses are the ventral medullary reticular formation, nucleus paragigantocellularis in the ventral medulla, periaqueductal gray, mesencephalic ventral tegmental area, neurons in the central tegmental mesencephalic region, the medial amygdala, and the medial preoptic area (MPOA). Central neurotransmitters include dopamine (enhances sexual desire, arousal), norepinephrine (gates sensory input from genitalia and maintains sexual arousal), acetylcholine (mediates lubrication and vaginal engorgement), histamine, serotonin (diminishes excitatory effects, interferes with arousal and orgasm), prolactin (causes sexual satiety and postorgasmic relief), oxytocin (promotes sexual receptivity and bonding). Peripheral sympathetic and parasympathetic pathways are similar in men and women. Hormones influence female sexual function. Progesterone furthers partner-receptivity, estrogens enhance desire, arousal, sensory thresholds, and genital arterial blood flow. Testosterone helps initiate sexual activity. FSD etiologies include psychogenic and psychiatric disorders; cardiovascular, neurological, muscular, endocrine problems; infectious diseases; or medications such as selective serotonin reuptake inhibitors (SSRIs), and many others. Therapeutic approaches of FSD mainly include psychoeducation, estrogen replacement, pain treatment physiotherapy, or biofeedback.
CRIS-Team Scopus Importer:2024-12-16
Keywords: Biofeedback; Estrogen replacement; Female sexual dysfunction; Female sexual function; Pain treatment physiotherapy; Psychoeducation

Physiotherapy improves motor function in patients with the Parkinson variant of multiple system atrophy: A prospective trial - Raccagni, C.; Goebel, G.; Gaßner, Heiko; Granata, Roberta; Ndayisaba, Jean Pierre; Seebacher, Barbara; Schoenherr, Gudrun; Mitterhuber, Jakob; Hendriks, Pascalle; Kaindlstorfer, Christine; Eschlboeck, Sabine; Fanciulli, Alessandra; et al. (Parkinsonism & Related Disorders, 2019)
Background and objectives: Gait impairment and reduced mobility are disabling symptoms of multiple system atrophy. While physiotherapy is increasingly recognized as a valuable supplement to pharmacotherapy for patients with Parkinson's disease, data on the efficacy of physiotherapy for multiple system atrophy are lacking. This study aimed to explore the feasibility of two consecutive exercise-based interventions in patients with multiple system atrophy. Subjects and Methods: We included 10 patients with the parkinsonian variant of multiple system atrophy and 10 patients with Parkinson's disease, matched for gender and Hoehn & Yahr stage (≤3). Interventions consisted of a five-day inpatient physiotherapy program followed by a five-week unsupervised home-based exercise program. Outcomes included instrumented gait analysis, patient questionnaires, clinical rating scales and physical tests. Patients were examined at baseline, after the first inpatient treatment and again after the home-based intervention. Additionally, a structured telephone interview was performed immediately after the second intervention period. Results: Both patient groups exhibited a similar improvement of gait after the interventions, as measured by instrumented gait analysis. These effects reached their maximum level after inpatient physiotherapy and remained stable following the home-based exercise program. Patient questionnaires also showed improvements after the interventions, but motor clinical rating scales did not. Conclusion: Our pilot results suggest that a short-term bout of physiotherapy is feasible, safe and improves gait performance in patients with multiple system atrophy. This highlights the potential of physiotherapy for this disabling condition where pharmacotherapy typically achieves poor effects. The present findings warrant a larger controlled study.
CRIS-Team Scopus Importer:2019-10-01
Keywords: Atypical parkinsonian disorders; Home-based training; Multiple system atrophy; Parkinson's disease; Physiotherapy

Pivotal Role for CD16+ Monocytes in Immune Surveillance of the Central Nervous System - Waschbisch, Anne; Schröder, Sina; Schraudner, Dana; Sammet, Laura; Weksler, Babette; Melms, Arthur; Pfeifenbring, Sabine; Stadelmann, Christine; Schwab, Stefan; Linker, Ralf A. (Journal of Immunology, 2016)
Monocytes represent a heterogeneous population of primary immune effector cells. At least three different subsets can be distinguished based on expression of the low-affinity Fc?RIII: CD14(++)CD16 -: classical monocytes, CD14(++)CD16(+) intermediate monocytes, and CD14(+)CD16 ++: non-classical monocytes. Whereas CD16 -: classical monocytes are considered key players in multiple sclerosis (MS), little is known on CD16(+) monocytes and how they contribute to the disease. In this study, we examined the frequency and phenotype of monocyte subpopulations in peripheral blood, cerebrospinal fluid (CSF), and brain biopsy material derived from MS patients and controls. Furthermore, we addressed a possible monocyte dysfunction in MS and analyzed migratory properties of monocyte subsets using human brain microvascular endothelial cells. Our ex vivo studies demonstrated that CD16(+) monocyte subpopulations are functional but numerically reduced in the peripheral blood of MS patients. CD16(+) monocytes with an intermediate-like phenotype were found to be enriched in CSF and dominated the CSF monocyte population under noninflammatory conditions. In contrast, an inversed CD16(+) to CD16 -: CSF monocyte ratio was observed in MS patients with relapsing-remitting disease. Newly infiltrating, hematogenous CD16(+) monocytes were detected in a perivascular location within active MS lesions, and CD16(+) monocytes facilitated CD4(+) T cell trafficking in a blood -: brain barrier model. Our findings support an important role of CD16(+) monocytes in the steady-state immune surveillance of the CNS and suggest that CD16(+) monocytes shift to sites of inflammation and contribute to the breakdown of the blood-brain barrier in CNS autoimmune diseases.
EVALuna2:22432

Pivotal role of choline metabolites in remyelination - Skripuletz, Thomas; Manzel, Arndt; Gropengieer, Karoline; Schaefer, Nora; Gudi, Viktoria; Singh, Vikramjeet; Tejedor, Laura Salinas; Joerg, Stefanie; Hammer, Anna; Voss, Elke; Vulinovic, Franca; Degen, Diane; et al. (Brain, 2015)
Neuroprotective approaches for central nervous system regeneration have not been successful in clinical practice so far and compounds that enhance remyelination are still not available for patients with multiple sclerosis. The objective of this study was to determine potential regenerative effects of the substance cytidine-5'-diphospho (CDP)-choline in two different murine animal models of multiple sclerosis. The effects of exogenously applied CDP-choline were tested in murine myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. In addition, the cuprizone-induced mouse model of de- and remyelination was used to specifically test the hypothesis that CDP-choline directly increases remyelination. We found that CDP-choline ameliorated the disease course of experimental autoimmune encephalomyelitis and exerted beneficial effects on myelin, oligodendrocytes and axons. After cuprizone-induced demyelination, CDP-choline effectively enhanced myelin regeneration and reversed motor coordination deficits. The increased remyelination arose from an increase in the numbers of proliferating oligodendrocyte precursor cells and oligodendrocytes. Further in vitro studies suggest that this process is regulated by protein kinase C. We thus identified a new mechanism to enhance central nervous system remyelination via the choline pathway. Due to its regenerative action combined with an excellent safety profile, CDP-choline could become a promising substance for patients with multiple sclerosis as an add-on therapy.
EVALuna2:22341

Plasma Neurofilaments: Potential Biomarkers of SPG11-Related Hereditary Spastic Paraplegia - Krumm, Laura; Winkler, Jürgen; Winner, Beate; Regensburger, Martin (Movement Disorders, 2024)
CRIS-Team Scopus Importer:2024-03-08

Plectin-related scapuloperoneal myopathy with treatment-responsive myasthenic syndrome - Argente-Escrig, H.; Schultheis, D.; Kamm, L.; Schowalter, M.; Thiel, C.; Türk, M.; Clemen, C. S.; Muelas, N.; Castañón, M. J.; Wiche, G.; Herrmann, H.; Vilchez, J. J.; et al. (Neuropathology and Applied Neurobiology, 2020)
CRIS-Team Scopus Importer:2020-08-28

Pointing in visual periphery: is DF's dorsal stream intact? - Hesse, Constanze; Ball, Keira; Schenk, Thomas (PLoS ONE, 2014)
Observations of the visual form agnosic patient DF have been highly influential in establishing the hypothesis that separate processing streams deal with vision for perception (ventral stream) and vision for action (dorsal stream). In this context, DF's preserved ability to perform visually-guided actions has been contrasted with the selective impairment of visuomotor performance in optic ataxia patients suffering from damage to dorsal stream areas. However, the recent finding that DF shows a thinning of the grey matter in the dorsal stream regions of both hemispheres in combination with the observation that her right-handed movements are impaired when they are performed in visual periphery has opened up the possibility that patient DF may potentially also be suffering from optic ataxia. If lesions to the posterior parietal cortex (dorsal stream) are bilateral, pointing and reaching deficits should be observed in both visual hemifields and for both hands when targets are viewed in visual periphery. Here, we tested DF's visuomotor performance when pointing with her left and her right hand toward targets presented in the left and the right visual field at three different visual eccentricities. Our results indicate that DF shows large and consistent impairments in all conditions. These findings imply that DF's dorsal stream atrophies are functionally relevant and hence challenge the idea that patient DF's seemingly normal visuomotor behaviour can be attributed to her intact dorsal stream. Instead, DF seems to be a patient who suffers from combined ventral and dorsal stream damage meaning that a new account is needed to explain why she shows such remarkably normal visuomotor behaviour in a number of tasks and conditions.
EVALuna2:22322

Polyhydroxyphenylvalerate/polycaprolactone nanofibers improve the life-span and mechanoresponse of human IPSC-derived cortical neuronal cells - Cerrone, Federico; Pozner, Tatyana; Siddiqui, Aarif; Ceppi, Paolo; Winner, Beate; Rajendiran, Murugan; Babu, Ramesh; Ibrahim, Hossam S.; Rodriguez, Brian J.; Winkler, Jürgen; Murphy, Keith J.; O'Connor, Kevin E. (Materials Science and Engineering C, 2020)
The physico-chemical characteristics of the extracellular matrix (ECM) cause mechanical cues that could elicit responses in the survival rate of cortical neuronal cells. Efficient neurite outgrowth in vitro, is critical for successful cultivation of cortical neuronal cells and the potential for attempts at regeneration of the central nervous system (CNS) in vivo. Relatively soft and hydrophilic, microbially synthesized aromatic polyester, polyhydroxyphenylvalerate (PHPV) was blended 50:50 with the stiff and hydrophobic polycaprolactone (PCL) and electrospun in microfibers for use in a 3D (CellCrown™) configuration and in a 2D coverslip coated configuration. This blend allows a 2.3-fold increase in the life-span of human induced pluripotent stem derived cortical neuronal cells (hiPS) compared to pure PCL fibers. HiPS-derived cortical neuronal cells grown on PHPV/PCL fibers show a 3.8-fold higher cumulative neurite elaboration compared to neurites grown on PCL fibers only. 96% of cortical neuronal cells die after 8 days of growth when plated on PCL fibers alone while >83% and 55% are alive on PHPV/PCL fibers on day 8 and day 17, respectively. An increased migration rate of cortical neuronal cells is also promoted by the blend compared to the PCL fibers alone. The critical survival rate improvement of hiPS derived cortical neuronal cells on PHPV/PCL blend holds promise in using these biocompatible nanofibers as implantable materials for regenerative purposes of an active cortical neuronal population after full maturation in vitro.
CRIS-Team Scopus Importer:2020-03-27
Keywords: Cortical neurons; Electrospinning; HiPSC; Mechanoresponse; Neuroregeneration; Polyhydroxyalkanoates

Position paper of a German interdisciplinary round table on future designs of trials on adjunctive treatment with antiseizure drugs - Hamer, Hajo; Holtkamp, Martin; Kaiser, Thomas; Fey, Susanne; Rozinat, Klaus; Mayer, Thomas; Schulze-Bonhage, Andreas (Seizure-European Journal of Epilepsy, 2020)
Purpose: Current trials on adjunctive treatment with antiseizure drugs often do not reveal results which are relevant for clinical practice. Method: Therefore, an interdisciplinary group of German experts discussed a new framework for future antiseizure drug (ASD) trials in adults. This group included members of the executive board of the German Society of Epileptology, of the German institutes for health technology assessment (HTA), of patient organizations and of drug manufacturers. Agreement was reached by consensus decision making after intensive discussion of the findings of a narrative review of the current literature. Results: The group jointly recommends that ASD trials in adults should be based on and include relevant patient groups, e.g. elderly patients and patients with relevant co-morbidities, should adopt a study duration of at least 12 months, should avoid placebo arms, should include active comparators of clinical relevance, may be designed as open label trials with blinded outcome measurements, should focus on patient relevant outcomes that reflect the impact of benefits and harms of treatments on daily living, such as seizure freedom and seizure severity as well as retention rate, functional outcomes and quality of life as compound measures, and should avoid arbitrary and non-sensitive primary endpoints such as dichotomized changes in seizure frequency. Conclusions: This paper focused on improved head-to-head trials on adjunctive treatment with antiseizure drugs. The group welcomes any further work and discussion to enhance future studies which can be applied to the entire spectrum of potentially meaningful study populations and outcomes.
CRIS-Team Scopus Importer:2020-03-27
Keywords: Active comparator; Antiseizure drugs/ASD; Outcome; Placebo; Trials

Possible second motor neuron damage in neuromyelitis optica - Laemmer, A. B.; Maihöfner, Christian; Gölitz, Philipp; Schwab, Sibylle; Lee, D. H.; Linker, R. A.; Schramm, Axel (Clinical Neurophysiology, 2014)
EVALuna2:22245

Posterior circulation ischemic stroke not involving the brainstem is associated with cardiovascular autonomic dysfunction - Wang, Ruihao; Kohrmann, Martin; Kollmar, Rainer; Köhn, Julia; Schwab, Stefan; Kallmünzer, Bernd; Hilz, Max-Josef (European Journal of Neurology, 2022)
Background and purpose Ischemic stroke may induce cardiovascular autonomic dysfunction, but most previous studies have included patients with anterior circulation ischemic stroke or brainstem stroke. It remains unclear whether posterior circulation ischemic stroke (PCIS) without brainstem involvement also compromises cardiovascular autonomic modulation (CAM). Therefore, we aimed to assess CAM in PCIS patients with and without brainstem involvement. Methods In four subgroups of 61 PCIS patients (14 occipital lobe, 16 thalamic, 12 cerebellar, and 19 brainstem strokes) and 30 healthy controls, we recorded RR intervals (RRIs), systolic (SBP) and diastolic blood pressure (DBP), and respiration at supine rest during the first week after stroke onset. We calculated parameters reflecting total CAM (RRI-standard deviation [RRI-SD], RRI-total powers), predominantly sympathetic CAM (RRI-low-frequency [LF] powers and SBP-LF powers] and parasympathetic CAM (root mean square of successive RRI differences [RMSSD], RRI-high-frequency [HF] powers), sympathetic-parasympathetic balance (RRI-LF/HF ratios), and baroreflex sensitivity (BRS). Values were compared among the four PCIS groups and controls using one-way ANOVA Kruskal-Wallis tests, with post-hoc analyses. Significance was assumed for p < 0.05. Results In each PCIS subgroup, values for RRI, RRI-SD, RMSSD, RRI-HF powers, and BRS were significantly lower, while SBP-LF powers were higher than in the controls. Only in patients with occipital lobe stroke were RRI-LF/HF ratios significantly higher than in controls. Otherwise, autonomic variables did not differ among the four PCIS subgroups. Conclusions During the first week after stroke onset, our PCIS patients with occipital lobe, thalamic, cerebellar, or brainstem strokes all had reduced cardiovagal modulation, compromised baroreflex, and increased peripheral sympathetic modulation. The RRI-LF/HF ratios suggest that sympathetic predominance is slightly more prominent after occipital lobe stroke. PCIS may trigger cardiovascular autonomic dysfunction even without brainstem involvement.
CRIS-Team WoS Importer:2022-06-24

Post-Stroke Cardiovascular Complications and Neurogenic Cardiac Injury: JACC State-of-the-Art Review - Sposato, Luciano A.; Hilz, Max-Josef; Aspberg, Sara; Murthy, Santosh B.; Bahit, M. Cecilia; Hsieh, Cheng Yang; Sheppard, Mary N.; Scheitz, Jan F. (Journal of the American College of Cardiology, 2020)
Over 1.5 million deaths worldwide are caused by neurocardiogenic syndromes. Furthermore, the consequences of deleterious brain-heart interactions are not limited to fatal complications. Cardiac arrhythmias, heart failure, and nonfatal coronary syndromes are also common. The brain-heart axis is implicated in post-stroke cardiovascular complications known as the stroke-heart syndrome, sudden cardiac death, and Takotsubo syndrome, among other neurocardiogenic syndromes. Multiple pathophysiological mechanisms with the potential to be targeted with novel therapies have been identified in the last decade. In the present state-of-the-art review, we describe recent advances in the understanding of anatomical and functional aspects of the brain-heart axis, cardiovascular complications after stroke, and a comprehensive pathophysiological model of stroke-induced cardiac injury.
CRIS-Team Scopus Importer:2020-12-04
Keywords: cardiovascular; inflammation; MACE; neurocardiogenic; stroke

Posttranslational modification and mutation of histidine 50 trigger alpha synuclein aggregation and toxicity - Xiang, Wei; Menges, Stefanie; Schlachetzki, Johannes; Meixner, Holger; Hoffmann, Anna-Carin; Schlötzer-Schrehardt, Ursula; Becker, Cord-Michael; Winkler, Jürgen; Klucken, Jochen; Klucken, Jochen (Molecular Neurodegeneration, 2015)
Aggregation and aggregation-mediated formation of toxic alpha synuclein (aSyn) species have been linked to the pathogenesis of sporadic and monogenic Parkinson's disease (PD). A novel H50Q mutation of aSyn, resulting in the substitution of histidine by glutamine, has recently been identified in PD patients. We have previously shown that the lipid peroxidation product 4-hydroxy-2-nonenal (HNE) induces the formation of HNE-aSyn adducts, thereby promoting aSyn oligomerization and increasing its extracellular toxicity to human dopaminergic neurons. Intriguingly, we identified histidine 50 (H50) of aSyn as one of the HNE modification target residues. These converging lines of evidence support the hypothesis that changes in H50 via posttranslational modification (PTM) and mutation trigger the formation of aggregated, toxic aSyn species, which interfere with cellular homeostasis. In the present study, we aim to elucidate 1) the role of H50 in HNE-mediated aSyn aggregation and toxicity, and 2) the impact of H50 mutation on aSyn pathology. Besides the PD-related H50Q, we analyze a PD-unrelated control mutation, in which H50 is replaced by an arginine residue (H50R).Analysis of HNE-treated aSyn revealed that H50 is the most susceptible residue of aSyn to HNE modification and is crucial for HNE-mediated aSyn oligomerization. Overexpression of aSyn with substituted H50 in H4 neuroglioma cells reduced HNE-induced cell damage, indicating a pivotal role of H50 in HNE modification-induced aSyn toxicity. Furthermore, we showed in vitro that H50Q/R mutations substantially increase the formation of high density and fibrillar aSyn species, and potentiate the oligomerization propensity of aSyn in the presence of a nitrating agent. Cell-based experiments also revealed that overexpression of H50Q aSyn in H4 cells promotes aSyn oligomerization. Importantly, overexpression of both H50Q/R aSyn mutants in H4 cells significantly increased cell death when compared to wild type aSyn. This increase in cell death was further exacerbated by the application of H2O2.A dual approach addressing alterations of H50 showed that either H50 PTM or mutation trigger aSyn aggregation and toxicity, suggesting an important role of aSyn H50 in the pathogenesis of both sporadic and monogenic PD.
EVALuna2:4709

Posttraumatic stress disorder in patients after transient ischemic attack: A one-year follow-up - Utz, Kathrin S.; Kiphuth, Ines C.; Schenk, Thomas (Journal of psychosomatic research, 2019)
Objective: We aimed to determine the prevalence of posttraumatic stress disorder (PTSD) 12 months after transient ischemic attack (TIA). Method: TIA patients of our previous investigation (examined 3 months after the event) were again examined 12 months after the diagnosis. PTSD and associated variables were assessed via self-rating instruments. Results: Eighty-four patients were included in the analyses. Twelve months after TIA the prevalence of probable PTSD was reduced (8.3%) compared to that found 3 months after TIA (29.6%). Coping assessed 3 months after TIA predicted long-term PTSD severity. Conclusion: Although the prevalence of probable PTSD decreased 12 months after experiencing a TIA compared to 3 months after TIA, prevalence of probable PTSD is still increased relative to that in the general population.
CRIS-Team Scopus Importer:2019-05-16
Keywords: Coping; Posttraumatic stress disorder; Quality of life; Transient ischemic attack

Postural Instability Inference in Parkinson's Disease Patients Using Wearable Sensors - Pasluosta, Cristian Federico; Barth, Jens; Gaßner, Heiko; Winkler, Jürgen; Klucken, Jochen; Eskofier, Björn (88th Congress of the Deutschen Gesellschaft für Neurologie mit Fortbildungsakademie (DGN), 2015)

Potential of Exosomes for the Treatment of Stroke - Hong, Shi Bin; Yang, Hua; Manaenko, Anatol; Lu, Jianfei; Mei, Qiyong; Hu, Qin (Cell Transplantation, 2019)
Stroke is the result of blockage or rupture of blood vessels in the brain and is the leading cause of death and disability in the world. Currently only a very limited number of therapeutic approaches are available for treatment of stroke patients, and the vast majority of neuroprotective agents that tested positively in pre-clinical studies failed in clinical trials. In recent years, the clinical value of the use of exosomes for stroke treatment has received widespread attention due their unique characteristics such as low immunogenicity, low toxicity and biodegradability, ability to cross the blood–brain barrier (BBB), and their important role in communication between cells. More and more evidence suggests that the secretion of exosomes is the mechanism underlying the protection induced by mesenchymal stromal cells (MSCs) after stroke. Exosomes are thought to support brain restoration and induce repairing effects, including neurovascular remodeling, and anti-apoptosis and anti-inflammatory effects. Recent reports have focused on the clinical application of exosomes as a potential drug delivery approach. This review focuses on the ability of exosomes to interrupt the stroke-induced pathologic processes of stroke, and on publications describing how to achieve more effective treatment of stroke with exosomes.
CRIS-Team Scopus Importer:2019-08-16
Keywords: exosome; microRNA; stroke

Potential of Sodium MRI as a Biomarker for Neurodegeneration and Neuroinflammation in Multiple Sclerosis - Huhn, Konstantin; Engelhorn, Tobias; Linker, Ralf A.; Nagel, Armin Michael (Frontiers in Neurology, 2019)
In multiple sclerosis (MS), experimental and ex vivo studies indicate that pathologic intra-and extracellular sodium accumulation may play a pivotal role in inflammatory as well as neurodegenerative processes. Yet, in vivo assessment of sodium in the microenvironment is hard to achieve. Here, sodium magnetic resonance imaging ((NaMRI)-Na-23) with its non-invasive properties offers a unique opportunity to further elucidate the effects of sodium disequilibrium in MS pathology in vivo in addition to regular proton based MRI. However, unfavorable physical properties and low in vivo concentrations of sodium ions resulting in low signal-to-noise-ratio (SNR) as well as low spatial resolution resulting in partial volume effects limited the application of (NaMRI)-Na-23. With the recent advent of high-field MRI scanners and more sophisticated sodium MRI acquisition techniques enabling better resolution and higher SNR, (NaMRI)-Na-23 revived. These studies revealed pathologic total sodium concentrations in MS brains now even allowing for the (partial) differentiation of intra-and extracellular sodium accumulation. Within this review we (1) demonstrate the physical basis and imaging techniques of (NaMRI)-Na-23 and (2) analyze the present and future clinical application of (NaMRI)-Na-23 focusing on the field of MS thus highlighting its potential as biomarker for neuroinflammation and -degeneration.
CRIS-Team WoS Importer:2019-02-22

Practical "1-2-3-4-Day" Rule for Starting Direct Oral Anticoagulants After Ischemic Stroke With Atrial Fibrillation: Combined Hospital-Based Cohort Study - Kimura, Shunsuke; Toyoda, Kazunori; Yoshimura, Sohei; Minematsu, Kazuo; Yasaka, Masahiro; Paciaroni, Maurizio; Werring, David J.; Yamagami, Hiroshi; Nagao, Takehiko; Yoshimura, Shinichi; Polymeris, Alexandros; Zietz, Annaelle; et al. (Stroke, 2022)
Background: The "1-3-6-12-day rule" for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severity. Methods: The combined data of prospective registries in Japan, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-nonvalvular atrial fibrillation (September 2011 to March 2014) and RELAXED (February 2014 to April 2016) were used. Patients were divided into transient ischemic attack and 3 stroke subgroups by the National Institutes of Health Stroke Scale score: mild (0-7), moderate (8-15), and severe (>= 16). The early treatment group was defined as patients starting DOACs earlier than the median initiation day in each subgroup. Outcomes included a composite of recurrent stroke or systemic embolism, ischemic stroke, and severe bleeding within 90 days. Six European prospective registries were used for validation. Results: In the 1797 derivation cohort patients, DOACs were started at median 2 days after transient ischemic attack and 3, 4, and 5 days after mild, moderate, and severe strokes, respectively. Stroke or systemic embolism was less common in Early Group (n=785)-initiating DOACS within 1, 2, 3, and 4 days, respectively-than Late Group (n=1012) (1.9% versus 3.9%; adjusted hazard ratio, 0.50 [95% CI, 0.27-0.89]), as was ischemic stroke (1.7% versus 3.2%, 0.54 [0.27-0.999]). Major bleeding was similarly common in the 2 groups (0.8% versus 1.0%). On validation, both ischemic stroke (2.4% versus 2.2%) and intracranial hemorrhage (0.2% versus 0.6%) were similarly common in Early (n=547) and Late (n=1483) Groups defined using derivation data. Conclusions: In Japanese and European populations, early DOAC initiation within 1, 2, 3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding. These findings support ongoing randomized trials to better establish the optimal timing of DOAC initiation.
CRIS-Team WoS Importer:2022-05-13

Pre- and Postictal Changes in the Innate Immune System: Cause or Effect? - Lang, Johannes; Olmes, David G.; Proske, Manuel; Hagge, Mareike; Dogan Onugoren, Mujgan; Rothhammer, Veit; Schwab, Stefan; Hamer, Hajo (European neurology, 2021)
Introduction: Recent studies have shown that inflammatory processes might play a role in epileptogenesis. Their role in ictogenesis is much less clear. The aim of this study was to investigate peri-ictal changes of the innate immune system by analyzing changes of immune cells, as well as pro- and anti-inflammatory cytokines. Methods: Patients with active epilepsy admitted for video-EEG monitoring for presurgical evaluation were included. Blood was sampled every 20 min for 5 h on 3 consecutive days until a seizure occurred. After a seizure, additional samples were drawn immediately, as well as 1 and 24 h later. To analyze the different populations of peripheral blood mononuclear cells, all samples underwent FACS for CD3, CD4, CD8, CD56, CD14, CD16, and CD19. For cytokine analysis, we used a custom bead-based multiplex immunoassay for IFN-gamma, IL-1 beta, IL-1RA, IL-4, IL-6, IL-10, IL-12, IL-17, MCP-1, MIP-1 alpha, and TNF alpha. Results: Fourteen patients with focal seizures during the sampling period were included. Natural killer (NK) cells showed a negative correlation (rho = -0.3362, p = 0.0195) before seizure onset and an immediate increase to 1.95-fold afterward. T helper (T-H) and B cells decreased by 2 and 8%, respectively, in the immediate postictal interval. Nonclassical and intermediate monocytes decreased not until 1 day after the seizures, and cytotoxic T (T-C) cells showed a long-lasting postictal increase by 4%. IL-10 and MCP-1 increased significantly after seizures, and IL-12 decreased in the postictal phase. Discussion/Conclusion: Our study argues for a role of the innate immune system in the pre- and postictal phases. NK cells might be involved in preictal changes or be altered as an epiphenomenon in the immediate preictal interval.
CRIS-Team WoS Importer:2021-07-09

Prediction of Recurrent Ischemic Stroke Using Registry Data and Machine Learning Methods: The Erlangen Stroke Registry - Vodencarevic, Asmir; Weingärtner, Michael; Caro, J. Jaime; Ukalovic, Dubravka; Zimmermann-Rittereiser, Marcus; Schwab, Stefan; Kolominsky-Rabas, Peter (Stroke, 2022)
BACKGROUND: There have been multiple efforts toward individual prediction of recurrent strokes based on structured clinical and imaging data using machine learning algorithms. Some of these efforts resulted in relatively accurate prediction models. However, acquiring clinical and imaging data is typically possible at provider sites only and is associated with additional costs. Therefore, we developed recurrent stroke prediction models based solely on data easily obtained from the patient at home. METHODS: Data from 384 patients with ischemic stroke were obtained from the Erlangen Stroke Registry. Patients were followed at 3 and 12 months after first stroke and then annually, for about 2 years on average. Multiple machine learning algorithms were applied to train predictive models for estimating individual risk of recurrent stroke within 1 year. Double nested cross-validation was utilized for conservative performance estimation and models' learning capabilities were assessed by learning curves. Predicted probabilities were calibrated, and relative variable importance was assessed using explainable artificial intelligence techniques. RESULTS: The best model achieved the area under the curve of 0.70 (95% CI, 0.64-0.76) and relatively good probability calibration. The most predictive factors included patient's family and housing circumstances, rehabilitative measures, age, high calorie diet, systolic and diastolic blood pressures, percutaneous endoscopic gastrotomy, number of family doctor's home visits, and patient's mental state. CONCLUSIONS: Developing fairly accurate models for individual risk prediction of recurrent ischemic stroke within 1 year solely based on registry data is feasible. Such models could be applied in a home setting to provide an initial risk assessment and identify high-risk patients early.
CRIS-Team Scopus Importer:2022-07-08
Keywords: ischemic stroke; machine learning; probability; recurrence; registries

Prediction of response to total sleep deprivation by autonomic heart rate parameters? - Rechlin, Thomas; Hegmann, Harald; Weis, Maria; Stemmler, Mark; Claus, Detlef; Kaschka, Wolfgang (Biological Psychiatry, 1995)
Keywords: Sleep deprivation; heart rate variability; autonomic parameters

Predictive Value Of Preoperative Magnetoencephalography (MEG) For Seizure Outcome In Surgery Of Long Term Epilepsy Associated Tumors - Roessler, K.; Heynold, Elisabeth; Kasper, Burkhard; Coras, R.; Blumcke, I.; Hamer, Hajo; Buchfelder, Michael; Rampp, Stefan (EPILEPSIA, 2019)
CRIS-Team WoS Importer:2019-11-15

Predictors of New Cerebral Microbleeds in Patients with Antiplatelet Drug Therapy - Wobith, Maria; Mayer, Christian; Belke, Marcus; Haag, Anja; Gerstner, Anja; Teepker, Michael; Strzelczyk, Adam; Werner, Rita; Hamer, Hajo; Rosenow, Felix; Menzler, Katja; Knake, Susanne (Journal of Stroke and Cerebrovascular Diseases, 2016)
Cerebral microbleeds (CMB) are associated with an increased risk for ischemic and especially hemorrhagic stroke. The aim of the present study is to identify patients at high risk for the development of new CMB after initiation of an antiplatelet drug therapy.Patients received magnetic resonance imaging (MRI) within 1 week after initiation of an antiplatelet drug treatment due to a first ischemic stroke (n = 58) and after a follow-up period of 6 months (n = 40). We documented the presence and the number of CMB at baseline and follow-up and analyzed the influence of possible risk factors including vascular risk factors, stroke etiology, and number of CMB at baseline using stepwise logistic regression and Spearman's correlation coefficient. We compared progression rates of CMB in relation to each risk factor using the Mann-Whitney U-test.The logistic regression model could correctly predict the presence of CMB in 70.7% of patients at baseline and 80% at follow-up. The model correctly identified 85% of patients with new CMB. We observed progression of CMB in 40% of the patients. The overall progression rate was .8 CMB per patient. The progression rate was significantly influenced by age more than 70 years and atherothrombotic stroke. The number of new CMB correlated significantly with the number of CMB at baseline.We found several predictors of CMB after initiation of antiplatelet drug therapy. The results help to identify patients who need closer monitoring and thorough control of risk factors in order to lower the risk of new CMB and associated complications.
EVALuna2:22489

Pre-existing parasympathetic dominance seems to cause persistent heart rate slowing after 6 months of fingolimod treatment in patients with multiple sclerosis - Hilz, Max-Josef; Canavese, Francesca; de Rojas Leal, Carmen; Lee, De Hyung; Linker, Ralf A.; Wang, Ruihao (Clinical Autonomic Research, 2024)
Purpose: Vagomimetic fingolimod effects cause heart rate (HR) slowing upon treatment initiation but wear off with sphingosine-1-phosphate receptor downregulation. Yet, prolonged HR slowing may persist after months of fingolimod treatment. We evaluated whether cardiovascular autonomic modulation differs before and 6 months after fingolimod initiation between patients with RRMS with and without initially prolonged HR slowing upon fingolimod initiation. Methods: In 34 patients with RRMS, we monitored RR intervals (RRI) and blood pressure (BP), at rest and upon standing up before fingolimod initiation. Six hours and 6 months after fingolimod initiation, we repeated recordings at rest. At the three time points, we calculated autonomic parameters, including RRI standard deviation (RRI-SD), RRI-total-powers, RMSSD, RRI high-frequency [HF] powers, RRI and BP low-frequency (LF) powers, and baroreflex sensitivity (BRS). Between and among patients with and without prolonged HR slowing upon fingolimod initiation, we compared all parameters assessed at the three time points (analysis of variance [ANOVA] with post hoc testing; significance: p < 0.05). Results: Six hours after fingolimod initiation, all patients had decreased HRs but increased RRIs, RRI-SDs, RMSSDs, RRI-HF-powers, RRI-total-powers, and BRS; 11 patients had prolonged HR slowing. Before fingolimod initiation, these 11 patients did not decrease parasympathetic RMSSDs and RRI-HF-powers upon standing up. After 6 months, all parameters had reapproached pretreatment values but the 11 patients with prolonged HR slowing had lower HRs while the other 23 patients had lower parasympathetic RMSSDs and RRI-HF-powers, and BRS than before fingolimod initiation. Conclusion: Our patients with prolonged HR slowing upon fingolimod initiation could not downregulate cardiovagal modulation upon standing up even before fingolimod initiation, and 6 months after fingolimod initiation still had more parasympathetic effect on HR while cardiovagal modulation and BRS were attenuated in the other 23 patients. Pre-existing parasympathetic predominance may cause prolonged HR slowing upon fingolimod initiation.
CRIS-Team Scopus Importer:2024-10-18
Keywords: Active standing; Fingolimod; Heart rate slowing; Parasympathetic predominance; Relapsing–remitting multiple sclerosis; Sphingosine-1-phosphate receptor

Pre-operative sensor-based gait parameters predict functional outcome after total knee arthroplasty - Kluge, Felix; Hannink, Julius; Pasluosta, C. F.; Klucken, Jochen; Gaßner, Heiko; Gelse, Kolja; Eskofier, Björn; Krinner, Sebastian (Gait & Posture, 2018)

Presence of Concomitant Systemic Cancer is Not Associated with Worse Functional Long-Term Outcome in Patients with Intracerebral Hemorrhage - Spuergel, Maximilian I.; Kuramatsu, Joji; Gerner, Stefan; Sembill, Jochen; Hartwich, Julius; Giede-Jeppe, Antje; Madzar, Dominik; Beuscher, Vanessa D.; Lücking, Hannes; Struffert, Tobias; Schwab, Stefan; Huttner, Hagen; et al. (Cerebrovascular Diseases, 2017)
Data on clinical characteristics and outcome of patients with intracerebral hemorrhage (ICH) and concomitant systemic cancer disease are very limited.Nine hundred and seventy three consecutive primary ICH patients were analyzed using our prospective institutional registry over a period of 9 years (2006-2014). We compared clinical and radiological parameters as well as outcome - scored using the modified Rankin Scale (mRS) and analyzed in a dichotomized fashion as favorable outcome (mRS = 0-3) and unfavorable outcome (mRS = 4-6) - of ICH patients with and without cancer. Relevant imbalances in baseline clinical and radiological characteristics were adjusted using propensity score (PS) matching.Prevalence of systemic cancer among patients with ICH was 8.5% (83/973). ICH patients with cancer were older (77 [70-82] vs. 72 [63-80] years; p = 0.002), had more often prior renal dysfunction (19/83 [22.9%] vs.107/890 [12.0%]; p = 0.005), and smaller hemorrhage volumes (10.1 [4.8-24.3] vs. 15.3 [5.4-42.9] mL; p = 0.017). After PS-matching there were no significant differences neither in mortality nor in functional outcome both at 3 months (mortality: 33/81 [40.7%] vs. 55/158 [34.8%]; p = 0.368; mRS = 0-3: 28/81 [34.6%] vs. 52/158 [32.9%]; p = 0.797) and 12 months (mortality: 39/78 [50.0%] vs. 70/150 [46.7%]; p = 0.633; mRS = 0-3: 25/78 [32.1%] vs. 53/150 [35.3%]; p = 0.620) among patients with and without concomitant systemic cancer. ICH volume tended to be highest in patients with hematooncologic malignancy and smallest in urothelial cancer.Patients with ICH and concomitant systemic cancer on average are older; however, they show smaller ICH volumes compared to patients without cancer. Yet, mortality and functional outcome is not different in ICH patients with and without cancer. Thus, the clinical history or the de novo diagnosis of concomitant malignancies in ICH patients should not lead to unjustified treatment restrictions.
EVALuna2:22553

Prevalence and impact on outcome of electrocardiographic early repolarization patterns among stroke patients: a prospective observational study - Bobinger, Tobias; Kallmünzer, Bernd; Kopp, Markus; Kurka, Natalia; Hilz, Max-Josef; Huttner, Hagen; Schwab, Stefan; Köhrmann, Martin; Arnold, Martin (Clinical Research in Cardiology, 2015)
Early repolarization pattern (ER) gained attention as a risk factor for ventricular arrhythmia and sudden cardiac death in the general population. While electrocardiographic abnormalities are frequent findings in stroke patients, data on ER pattern in this population are lacking.We assessed the prevalence of ER pattern in consecutive acute stroke patients at a tertiary stroke center. Functional outcome after 90 days was analyzed to determine the effect of an ER pattern on mortality. Multivariate logistic regression analysis was used to identify factors associated with an ER pattern.Out of 1141 consecutive stroke patients 771 patients remained for analysis after application of exclusion criteria. ER was observed in 62 (8.04%) patients. ER was more prevalent among subjects with intracerebral and subarachnoidal hemorrhage (13.0%) than among patients with ischemic stroke (7.0%; p = 0.024). Multiple regression analysis revealed QRS-duration (OR 0.972 95% CI 0.950-0.994, p = 0.012), QT-duration (OR 1.009, 95% CI 1.004-1.014, p = 0.001) and mechanical ventilation on admission (OR 0.320, 95% CI 0.136-0.752, p = 0.009) as independent predictors for ER. Overall ER on admission was not associated with increased mortality at 3-month follow-up (ER 11.3% vs. non-ER 9.2%; p = 0.582).ER is frequently found among patients with acute cerebrovascular events and is more prevalent in patients with hemorrhagic compared to ischemic events. Our study yields no evidence that ER is associated with worse outcome or mortality after stroke.
EVALuna2:12024

Prevalence and influencing factors of chronic post-traumatic stress disorder in patients with myocardial infarction, transient ischemic attack (TIA) and stroke – an exploratory, descriptive study - Dollenberg, Aurora; Moeller, Sebastian; Lücke, Caroline; Wang, Ruihao; Lam, Alexandra P.; Philipsen, Alexandra; Gschossmann, Jürgen; Hoffmann, Falk; Müller, Helge H.O. (BMC Psychiatry, 2021)
Background: Cardio- and cerebrovascular events such as myocardial infarction (MI), stroke and transient ischemic attack (TIA) are leading causes of death and disability and have also been associated with poor mental outcomes. In addition, cardio- and cerebrovascular events may pose the risk of experiencing a sudden traumatic occurrence of symptoms during ictus and thus contribute to high rates of PTSD as well as high rates of subsequent depression and anxiety. Moreover, MI, TIA and stroke survivors with PTSD, depressive and anxiety symptoms may have poorer health-related quality of life (HRQoL) and poorer disease prognosis than patients who do not develop psychiatric symptoms after ictus. However, data on the prevalence of PTSD, anxiety and depression, as well as the HRQoL, coping strategies and potential risk factors for development of PTSD in these patients, are rare. Methods: In an exploratory, descriptive study we interviewed 112 patients (54 MI, 18 TIA, 40 stroke; mean age: 69.5 years, 55.4% males) from three general physician practices and used psychometric self-assessment tools to determine the occurrence of PTSD and psychosomatic comorbidity, anxiety and depression and to assess HRQoL and coping strategies. We evaluated disease severity and compared the patient groups to each other. Moreover, we assessed psychological outcome differences between patients with or without PTSD after ictus. Results: The prevalence of PTSD after MI, TIA and stroke was 23.2%. The patients who developed PTSD had higher rates of depression, anxiety and maladaptive coping as well as reduced HRQoL. Adaptive coping was positively related to better mental HRQoL and negatively related to anxiety and depression. Disease severity of MI, TIA and stroke was not related to PTSD, depression, anxiety or physical HRQoL. Conclusions: Experiencing MI, TIA or stroke means confronting a life-threatening event for those affected and, therefore, these can be regarded as traumatic events. Cerebral and cardiovascular events increase the risk of developing chronic PTSD with subsequent increased depression and anxiety and reduced HRQoL. These findings emphasize the need for early screening and diagnosis of PTSD in somatically ill patients, which should be followed by specialized treatment, as PTSD hampers overall (somatic) disease prognosis. Trial registration: German Clinical Trials Register, DRKS00021730, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021730, registered 05/19/2020 - Retrospectively registered.
CRIS-Team Scopus Importer:2021-06-18
Keywords: Anxiety; Coping strategies; Depression; HRQoL; Myocardial infarction; PTSD; Stroke; TIA

Prevalence of sport injuries in Olympic combat sports: a cross-sectional study examining one Olympic period - Lambert, Christophe; Ritzmann, Ramona; Lambert, Sheena; Lachmann, Daniel; Malliaropoulos, Nikolaos G.; Gesslein, Markus; Peters, Nicholas; Shafizadeh, Sven (Journal of Sports Medicine and Physical Fitness, 2022)
BACKGROUND: Due to full contact impacts in combat sports, the risk of injuries is elevated. The aim of this study is to report severe injuries among athletes in Olympic combat sports. Specific injury types, time loss, and the performance level after injury are examined. METHODS: Survey to investigate injuries in Olympic combat sports during the time period from 2012-2016. Reported injuries were analyzed by anatomical location, injury type, gender, time loss, and performance level. RESULTS: The three injuries resulting in the longest time loss (ACL rupture: judo= 37 weeks; karate = 49 weeks; shoulder dislocation: wrestling = 41 weeks; shoulder rotator cuff injury: wrestling = 32 weeks) also accounted for the largest proportion of athletes with career-ending injuries (ACL rupture: judo = 28%; karate = 67%; shoulder dislocation: wrestling = 40%; shoulder rotator cuff injury: wrestling = 50%). Taekwondo and fencing had the shortest time loss (<12 weeks) among all combat sports. More injuries occurred during training (58%) as compared to competition (42%). Injury prevalence of competitive athletes was significantly higher as compared to recreational athletes. Male athletes suffered significantly more anterior cruciate ligament injuries (72% vs. 56%; P<0.05), unspecific shoulder injuries (89% vs. 47%; P<0.01), and elbow ligament injuries (57% vs. 30%; P<0.05) during training. CONCLUSIONS: The study shows that there are important differences between "punching and kicking" and "throwing" martial arts in terms of specific injury types. In judo and wrestling, the injuries are more likely to affect the joints (knee and shoulder). Therefore, injury prevention these sports should focus on strength training of the muscles surrounding the joints and on defensive reactionary movements to avoid dangerous biomechanical joint angles. In "punching and kicking" sports, injuries of the hands and feet, due to the large impact forces of strikes and kicks, could be reduced by improved protective equipment on hands and feet.
CRIS-Team Scopus Importer:2022-11-04

Prevalence, utilization, and costs of antiepileptic drugs for epilepsy in Germany – a nationwide population-based study in children and adults - Hamer, Hajo; Dodel, Richard; Strzelczyk, Adam; Balzer-Geldsetzer, Monika; Reese, Jens-Peter; Schöffski, Oliver; Graf, Wolfgang; Schwab, Stefan; Knake, Susanne; Oertel, Wolfgang; Rosenow, Felix; Kostev, Karel (Journal of Neurology, 2012)
<h2 class="Heading" style="border: 0px; font-weight: 400; font-stretch: inherit; font-size: 24px; line-height: 1.2; font-family: Georgia, 'New Century Schoolbook', 'Nimbus Roman No9 L', serif; margin: 7px 0px; padding: 0px; vertical-align: baseline; outline: 0px; letter-spacing: 0.02em; width: 580px; color: rgb(51, 51, 51);"> Nationwide analyses of drug use can provide a prevalence estimate of the underlying disease and can help in understanding the characteristics of treatment. This study aimed for such analyses regarding the utilization of antiepileptic drugs (AED) for epilepsy in Germany. In 2009, all 4,115,705 AED prescriptions of all German patients with statutory health insurance (70,011,508 persons) were retrospectively analyzed. The IMS® LRx database served as data source, which accesses nationwide pharmacy data centers processing all German prescription data. To establish the age and sex-specific percentage of patients taking AED because of epilepsy, we used a second database, Disease Analyzer®, which covered a representative sample of the German population (7.2 million patients) and contained ICD10 codes alongside with prescription data. The period prevalence of patients taking AED because of epilepsy was 9.1/1,000 (children/adolescents: 5.2/1,000; elderly: 12.5/1,000). Of the patients, 83.1 % took at least one of four AED: valproate (29.8 %), carbamazepine (26.4 %), lamotrigine (21.4 %), and levetiracetam (16.9 %). Oxcarbazepine and sultiame were popular with pediatricians. Elderly patients frequently received phenytoin and primidone. More than half of the patients were treated by family physicians; 68 % took AED in monotherapy and 7.9 % received >2 AED (children/adolescents: 12.5 %). The costs for AED prescribed for epilepsy amounted to €285.1 Mio (median AED costs/patient: €158/a). The German 2009 prevalence of epileptic patients taking AED was 9.1/1,000. Family physicians cared for the majority of patients. Prevalence and prescribing patterns changed with age. Costs of AED against epilepsy added up to 1 % of total medication costs in Germany.
WiSo-Import:2015-03-26:4184
Keywords: Epilepsy; Prevalence; Antiepileptic drugs; Costs; Children; Elderly

Primary cilia and SHH signaling impairments in human and mouse models of Parkinson's disease - Schmidt, Sebastian; Luecken, Malte D.; Truembach, Dietrich; Hembach, Sina; Niedermeier, Kristina M.; Wenck, Nicole; Pfluegler, Klaus; Stautner, Constantin; Boettcher, Anika; Lickert, Heiko; Ramirez-Suastegui, Ciro; Ahmad, Ruhel; et al. (Nature Communications, 2022)
Parkinson's disease (PD) as a progressive neurodegenerative disorder arises from multiple genetic and environmental factors. However, underlying pathological mechanisms remain poorly understood. Using multiplexed single-cell transcriptomics, we analyze human neural precursor cells (hNPCs) from sporadic PD (sPD) patients. Alterations in gene expression appear in pathways related to primary cilia (PC). Accordingly, in these hiPSC-derived hNPCs and neurons, we observe a shortening of PC. Additionally, we detect a shortening of PC in PINK1-deficient human cellular and mouse models of familial PD. Furthermore, in sPD models, the shortening of PC is accompanied by increased Sonic Hedgehog (SHH) signal transduction. Inhibition of this pathway rescues the alterations in PC morphology and mitochondrial dysfunction. Thus, increased SHH activity due to ciliary dysfunction may be required for the development of pathoetiological phenotypes observed in sPD like mitochondrial dysfunction. Inhibiting overactive SHH signaling may be a potential neuroprotective therapy for sPD.
CRIS-Team WoS Importer:2022-08-26

Probable Autoimmune Catatonia With Antibodies Against Cilia on Hippocampal Granule Cells and Highly Suspicious Cerebral FDG-Positron Emission Tomography Findings - Endres, Dominique; Prüss, Harald; Rauer, Sebastian; Süß, Patrick; Venhoff, Nils; Feige, Bernd; Schweizer, Tina; Nickel, Kathrin; Maier, Simon; Egger, Karl; Domschke, Katharina; Meyer, Philipp T.; et al. (Biological Psychiatry, 2020)
CRIS-Team Scopus Importer:2020-04-14

Probable Autoimmune Depression in a Patient With Multiple Sclerosis and Antineuronal Antibodies - Endres, Dominique; Rauer, Sebastian; Venhoff, Nils; Süß, Patrick; Dersch, Rick; Runge, Kimon; Fiebich, Bernd L.; Nickel, Kathrin; Matysik, Miriam; Maier, Simon; Domschke, Katharina; Egger, Karl; et al. (Frontiers in Psychiatry, 2020)
Background: In a subgroup of patients with mood disorders, clear-cut organic disorders are responsible for depressive symptoms (e.g., autoimmune diseases such as multiple sclerosis or systemic lupus erythematosus). In these cases, an organic affective disorder can be diagnosed. Case Presentation: The authors present the case of a 59-year-old male patient who developed a severe depressive episode over approximately 6 months and was, therefore, admitted to the hospital. In retrospect, he reported that, at age 39, he suffered from self-limiting sensory disturbances and muscle weakness in both legs. The current magnetic resonance imaging of his brain showed several conspicuous FLAIR-hyperintense supratentorial white matter lesions compatible with chronic inflammatory brain disease. Imaging of the spinal axis revealed no clear spinal lesions. Cerebrospinal fluid (CSF) analyses showed CSF-specific oligoclonal bands. Therefore, multiple sclerosis was diagnosed. Further CSF analyses, using tissue-based assays with indirect immunofluorescence on unfixed murine brain tissue, revealed a (peri-)nuclear signal and a strong neuritic signal of many neurons, especially on granule cells in the cerebellum, hippocampus, and olfactory bulb, as well as in the corpus callosum. Additionally, antinuclear antibody (ANA) titers of 1:12,800 and a lymphopenia were detected in blood tests. Further system clarification showed no suspicion of rheumatic or oncological disease. Anti-inflammatory treatment led to rapid and sustained improvement. Conclusion: The present patient suffered from a probable “autoimmune depression” in the context of newly diagnosed multiple sclerosis with typical MRI and CSF pathologies, alongside mild concomitant latent systemic autoimmune process (with high-titer ANAs and lymphopenia) and unknown antineuronal antibodies. The case report illustrates that a depressive syndrome suggestive of primary idiopathic depressive disorder may be associated with an autoimmune brain involvement. The detection of such organic affective disorders is of high clinical relevance for affected patients, as it enables alternative and more causal treatment approaches.
CRIS-Team Scopus Importer:2020-09-11
Keywords: autoantibody; autoimmune encephalitis; connective tissue disease; depression; multiple sclerosis

Prognosis of pacing-dependent patients with cardiovascular implantable electronic devices - Grimm, Wolfram; Erdmann, Barbara; Grimm, Kathrin; Kreutz, Julian; Parahuleva, Mariana (Herzschrittmachertherapie und Elektrophysiologie, 2024)
Background: Data on the prognostic significance of pacing dependency in patients with cardiovascular implantable electronic devices (CIEDs) are sparse. Methods: The prognostic significance of pacing dependency defined as absence of an intrinsic rhythm ≥ 30 bpm was determined in 786 patients with CIEDs at the authors’ institution using univariate and multivariate regression analysis to identify predictors of all-cause mortality. Results: During 49 months median follow-up, death occurred in 63 of 130 patients with pacing dependency compared to 241 of 656 patients without pacing dependency (48% versus 37%, hazard ratio [HR] 1.34; 95% confidence interval [CI]: 1.02–1.78, P = 0.04). Using multivariate regression analysis, predictors of all-cause mortality included age (HR 1.07; 95% CI: 1.05–1.08, P < 0.01), history of atrial fibrillation (HR 1.32, 95% CI: 1.03–1.69, P < 0.01), chronic kidney disease (HR 1.28; 95% CI: 1.00–1.63, P = 0.048) and New York Heart Association (NYHA) class ≥ III (HR 2.00; 95% CI: 1.52–2.62, P < 0.01), but not pacing dependency (HR 1.15; 95% CI: 0.86–1.54, P = 0.35). Conclusions: In contrast to age, atrial fibrillation, chronic kidney disease and heart failure severity as indexed by NYHA functional class III or IV, pacing dependency does not appear to be an independent predictor of all-cause mortality in patients with CIEDs.
CRIS-Team Scopus Importer:2024-02-16
Keywords: Chronic kidney disease; Heart failure; Implantable cardioverter-defibrillator; Pacing dependency; Permanent pacemaker

Prognostic Accuracy of CTP Summary Maps in Patients with Large Vessel Occlusive Stroke and Poor Revascularization after Mechanical Thrombectomy-Comparison of Three Automated Perfusion Software Applications - Mühlen, Iris; Borutta, Matthias; Siedler, Gabriela; Engelhorn, Tobias; Hock, Stefan; Knott, Michael; Hölter, Philip; Volbers, Bastian; Schwab, Stefan; Dörfler, Arnd (Tomography, 2022)
Background: Innovative automated perfusion software solutions offer support in the management of acute stroke by providing information about the infarct core and penumbra. While the performance of different software solutions has mainly been investigated in patients with successful recanalization, the prognostic accuracy of the hypoperfusion maps in cases of futile recanalization has hardly been validated. Methods: In 39 patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation and poor revascularization (thrombolysis in cerebral infarction (TICI) 0-2a) after mechanical thrombectomy (MT), hypoperfusion analysis was performed using three different automated perfusion software solutions (A: RAPID, B: Brainomix e-CTP, C: Syngo.via). The hypoperfusion volumes (HV) as Tmax > 6 s were compared with the final infarct volumes (FIV) on follow-up CT 36-48 h after futile recanalization. Bland-Altman analysis was applied to display the levels of agreement and to evaluate systematic differences. Based on the median hypoperfusion intensity ratio (HIR, volumetric ratio of tissue with a Tmax > 10 s and Tmax > 6 s) patients were dichotomized into high- and low-HIR groups. Subgroup analysis with favorable (<0.6) and unfavorable (>= 0.6) HIR was performed with respect to the FIV. HIR was correlated to clinical baseline and outcome parameters using Pearson's correlation. Results: Overall, there was good correlation without significant differences between the HVs and the FIVs with package A (r = 0.78, p < 0.001) being slightly superior to B and C. However, levels of agreement were very wide for all software applications in Bland-Altman analysis. In cases of large infarcts exceeding 150 mL the performance of the automated software solutions generally decreased. Subgroup analysis revealed the FIV to be generally underestimated in patients with HIR >= 0.6 (p < 0.05). In the subgroup with favorable HIR, however, there was a trend towards an overestimation of the FIV. Nevertheless, packages A and B showed good correlation between the HVs and FIVs without significant differences (p > 0.2), while only package C significantly overestimated the FIV (-54.6 +/- 56.0 mL, p = 0.001). The rate of modified Rankin Scale (mRS) 0-3 after 3 months was significantly higher in favorable vs. unfavorable HIR (42.1% vs. 13.3%, p = 0.02). Lower HIR was associated with higher Alberta Stroke Program Early CT Score (ASPECTS) at presentation and on follow-up imaging, lower risk of malignant edema, and better outcome (p < 0.05). Conclusion: Overall, the performance of the automated perfusion software solutions to predict the FIV after futile recanalization is good, with decreasing accuracy in large infarcts exceeding 150 mL. However, depending on the HIR, FIV can be significantly over- and underestimated, with Syngo showing the widest range. Our results indicate that the HIR can serve as valuable parameter for outcome predictions and facilitate the decision whether or not to perform MT in delicate cases.
CRIS-Team WoS Importer:2022-07-08

Prognostication after intracerebral hemorrhage: a review. - Witsch, Jens; Siegerink, Bob; Nolte, Christian H.; Sprügel, Maximilian; Steiner, Thorsten; Endres, Matthias; Huttner, Hagen (Neurological Research and Practice, 2021)
BACKGROUND: Approximately half of patients with spontaneous intracerebral hemorrhage (ICH) die within 1 year. Prognostication in this context is of great importance, to guide goals of care discussions, clinical decision-making, and risk stratification. However, available prognostic scores are hardly used in clinical practice. The purpose of this review article is to identify existing outcome prediction scores for spontaneous intracerebral hemorrhage (ICH) discuss their shortcomings, and to suggest how to create and validate more useful scores. MAIN TEXT: Through a literature review this article identifies existing ICH outcome prediction models. Using the Essen-ICH-score as an example, we demonstrate a complete score validation including discrimination, calibration and net benefit calculations. Score performance is illustrated in the Erlangen UKER-ICH-cohort (NCT03183167). We identified 19 prediction scores, half of which used mortality as endpoint, the remainder used disability, typically the dichotomized modified Rankin score assessed at variable time points after the index ICH. Complete score validation by our criteria was only available for the max-ICH score. Our validation of the Essen-ICH-score regarding prediction of unfavorable outcome showed good discrimination (area under the curve 0.87), fair calibration (calibration intercept 1.0, slope 0.84), and an overall net benefit of using the score as a decision tool. We discuss methodological pitfalls of prediction scores, e.g. the withdrawal of care (WOC) bias, physiological predictor variables that are often neglected by authors of clinical scores, and incomplete score validation. Future scores need to integrate new predictor variables, patient-reported outcome measures, and reduce the WOC bias. Validation needs to be standardized and thorough. Lastly, we discuss the integration of current ICH scoring systems in clinical practice with the awareness of their shortcomings. CONCLUSION: Presently available prognostic scores for ICH do not fulfill essential quality standards. Novel prognostic scores need to be developed to inform the design of research studies and improve clinical care in patients with ICH.
EVALuna2:470180
Keywords: Cerebrovascular disease; Stroke; Intracerebral hemorrhage; Prognosis; Outcome research

Prognostic factors in ALS: a comparison between Germany and China - Dorst, Johannes; Chen, Lu; Rosenbohm, Angela; Dreyhaupt, Jens; Hübers, Annemarie; Schuster, Joachim; Weishaupt, Jochen H.; Kassubek, Jan; Gess, Burkhard; Meyer, Thomas; Weyen, Ute; Hermann, Andreas; et al. (Journal of Neurology, 2019)
Objective: Several independent prognostic factors, such as age of onset, type of onset, body mass index (BMI), and progression rate have been identified for amyotrophic lateral sclerosis (ALS) in Caucasians. The aim of this study was to identify such factors in Chinese patients and to compare their impact with German patients. Methods: Comparison of prognostic factors was based on two hospital-based registries. The registry of the German Network for Motor Neuron Diseases contains 3100 patients with ALS. The Chinese registry comprises 2101 patients who were collected between 2003 and 2015 in the metropolitan area of Beijing. Results: Disease progression was slower in China [median loss of 0.50 points (IQR 0.26–0.87 points) versus 0.55 points (IQR 0.28–1.00 points) of ALS functional rating scale revised (ALS-FRS-R) score per month; p < 0.0001]. Survival of patients with ALS was similar in Germany and China (p > 0.05). We found that younger age of onset (p < 0.0001), spinal onset (p < 0.0001), high BMI (p < 0.0001) and low progression rate (p < 0.0001) were positive prognostic factors in China as well as in Germany. Interpretation: Prognostic factors, which are known to modify the course of disease in Caucasians, apply to Chinese patients as well. The results indicate that despite the apparent differences regarding genotype and clinical phenotype, findings from interventional studies in Caucasians aiming at disease-modifying prognostic factors (such as body weight) may be transferred to Chinese patients.
CRIS-Team Scopus Importer:2019-05-02
Keywords: Amyotrophic lateral sclerosis; China; Germany; Motor neuron disease; Prognostic factors; Survival

Prognostic influence of witness/victim experiences and PTSD-specific symptoms on working and educational capacity: a comparison between two groups of individuals post-trauma - Mueller, Helge H.; Möller, Sebastian; Hilger, York; Sperling, Wolfgang (Annals of General Psychiatry, 2015)
Trauma exposure depends of the type of trauma and can result in the development of posttraumatic stress disorder (PTSD). The type of traumatization (such as Holocaust experiences and other sources of trauma) and specific symptoms of PTSD have influences on the outcome, and specific symptoms of PTSD influence personal and professional outcomes. Another factor is the role of the victim in their traumatization. Some patients are actively traumatized through being victims of torture, while others are passively traumatized by witnessing the traumatization of others.We compared two groups of victim/witness trauma sufferers (PTSD vs. Holocaust-experience PTSD (HE-PTSD)) with regard to PTSD symptoms, educational and working capacity, and functional outcome parameters.HE-PTSD survivors with victim/witness trauma experience showed substantially more specific PTSD symptoms and higher symptom-specific intensities but had high social function and education levels. The intensity and type of intrusive memories and sociodemographic factors do not seem to have a prognostic influence on working or educational outcomes.Identifying the combined victim/witness experience seems to play an important prognostic role in the assessment of PTSD victims. Further studies should consider these findings within other specific traumatization groups.
EVALuna2:22275

Programmed Cell Death after Intracerebral Hemorrhage - Bobinger, Tobias; Burkardt, Petra; Huttner, Hagen; Manaenko, Anatol (Current Neuropharmacology, 2018)
BACKGROUND: Intracerebral hemorrhage (ICH) accounts for up to 15% of all strokes and is characterized by high rates of mortality and morbidity. The post-ICH brain injury can be distinguished in 1) primary, which are caused by disruption and mechanical deformation of brain tissue due to hematoma growth and 2) secondary, which are induced by microglia activation, mitochondrial dysfunction, neurotransmitter and inflammatory mediator release. Although these events typically lead to necrosis, the occurrence of programmed cell death has also been reported after ICH. METHODS: We reviewed recent publications describing advance in pre- and clinic ICH research. RESULTS: At present, treatment of ICH patients is based on oral anticoagulant reversal, management of blood pressure and other medical complications. Several pre-clinical studies showed promising results and demonstrated that anti-oxidative and anti-inflammatory treatments reduced neuronal cell death, however, to date, all of these attempts have failed in randomized controlled clinical trials. Yet, the time frame of administration may be crucial in translation from animal to clinical studies. Furthermore, the latest pre-clinical research points toward the existence of other, apoptosisunrelated forms kinds of programmed cell death. CONCLUSION: Our review summarizes current knowledge of pathways leading to programmed cell death after ICH in addition to data from clinical trials. Some of the pre-clinical results have not yet demonstrated clinical confirmation, however they significantly contribute to our understanding of post-ICH pathology and can contribute to development of new therapeutic approaches, decreasing mortality and improving ICH patients' quality of life.
EVALuna2:36546

PROPHYLACTIC AND PROLONGED HYPOTHERMIA IN POOR-GRADESAH REDUCES DEGREE OF VASOSPASM AND RATE OF DELAYED CEREBRAL INFARCTIONS - Kuramatsu, J. B.; Kollmar, Rainer; Staykov, Dimitre; Kloska, Stephan; Dörfler, Arnd; Eyüpoglu, Ilker Yasin; Schwab, Stefan; Huttner, Hagen (2016)
EVALuna2:22484

Propionate induced bacterial-derived histamine promotes resolution of synovial inflammation - Dürholz, Kerstin; Lucas, Sébastien; Schmid, Eva; Schaelter, F.; Frech, Michael; Azizov, Vugar; Hofmann, Jörg; Iljazovic, A.; Strowig, T.; Taudte, Verena; Fromm, Martin; Xiang, Wei; et al. (EUROPEAN JOURNAL OF IMMUNOLOGY, 2022)
CRIS-Team WoS Importer:2023-01-27

Propionic Acid Rescues High-Fat Diet Enhanced Immunopathology in Autoimmunity via Effects on Th17 Responses - Haase, Stefanie; Mäuerer, Jonas; Duscha, Alexander; Lee, De-Hyung; Balogh, Andras; Gold, Ralf; Mueller, Dominik N.; Haghikia, Aiden; Linker, Ralf A. (Frontiers in Immunology, 2021)
High-fat diets (HFD) are linked to obesity and associated comorbidities and induce pathogenic T helper (Th) 17 cells while decreasing regulatory T cells (Treg). This pro-inflammatory environment also aggravates immunopathology in experimental autoimmune encephalomyelitis (EAE) as a prototype model of T cell mediated autoimmunity. The strong association of HFD to obesity as well as the increasing risk of autoimmunity in the Western world stresses the importance to identify compounds that counteract this metabolically induced pro-inflammatory state in humans. One prominent candidate is the short-chain fatty acid propionate (PA) that was recently identified as potent therapy in the autoimmune disease multiple sclerosis by enhancing Treg cell frequencies and functionality. Mice were fed a HFD rich lauric acid (LA) and treated either with water or PA during MOG35-55-EAE. We analyzed Treg and Th17 cell frequencies in different tissues, antigen-specific cell proliferation and cytokine secretion, investigated Treg cell functionality by suppression assays and IL-10 signaling blockade and employed Western blotting to investigate the involvement of p38-MAPK signaling. Finally, we performed an explorative study in obese and non-obese MS patients, investigating fecal PA concentrations as well as peripheral Th17 and Treg frequencies before and after 90 days of daily PA intake. As compared to controls, mice on a HFD displayed a more severe course of EAE with enhanced demyelination and immune cell infiltration in the spinal cord. PA treatment prevented this disease enhancing effect of HFD by inhibiting Th17 mediated inflammatory processes in the gut and the spleen. Blocking experiments and signaling studies revealed p38-MAPK and IL-10 signaling as important targets linking the beneficial effects of PA treatment and reduced inflammation due to enhanced Treg frequency and functionality. An explorative study in a small group of MS patients revealed reduced PA concentrations in fecal samples of obese MS patients compared to the non-obese group, coinciding with increased Th17 but decreased Treg cells in obese patients. Importantly, PA intake could restore the Treg-Th17 homeostasis. Our data thus identify Th17 responses as an important target for the beneficial effects of PA in HFD and obesity in addition to the recently identified potential of PA as a Treg inducing therapy in T cell mediated autoimmunity.
CRIS-Team Scopus Importer:2021-06-25
Keywords: EAE; high-fat diet; immunosuppression; multiple sclerosis; propionic acid

Propofol-related urine discoloration in a patient with fatal atypical intracerebral hemorrhage treated with hypothermia - Regensburger, Martin; Huttner, Hagen; Dörfler, Arnd; Schwab, Stefan; Staykov, Dimitre (SpringerPlus, 2014)
Introduction: Mild therapeutic hypothermia is an increasingly recognised treatment option to reduce perihemorrhagic edema in severe intracerebral hemorrhage. Case description: We report the case of a 77-year old woman with atypical intracerebral hemorrhage that was treated with mild hypothermia in addition to osmotic therapy. The patient’s urine subsequently showed a green discoloration. Urine discoloration was completely reversible upon discontinuation of propofol. Discussion and evaluation: Propofol-related urine discoloration may have been provoked by hypothermia. Due to the benign nature of this side effect, propofol should be stopped and gastrointestinal function should be supported. Conclusion: More studies are needed to show a causal role of hypothermia and related decreased enzymatic function.
CRIS-Team Scopus Importer:2021-08-17
Keywords: Enterohepatic circulation; Hypothermia; Intracerebral hemorrhage; Liver enzyme function; Urine discoloration

Proposal: different types of alteration and loss of consciousness in epilepsy - Lueders, Hans; Amina, Shahram; Bailey, Christopher; Baumgartner, Christoph; Benbadis, Selim; Bermeo, Adriana; Carreno, Maria; Devereaux, Michael; Diehl, Beate; Eccher, Matthew; Edwards, Jonathan; Fastenau, Philip; et al. (Epilepsia, 2014)
There are at least five types of alterations of consciousness that occur during epileptic seizures: auras with illusions or hallucinations, dyscognitive seizures, epileptic delirium, dialeptic seizures, and epileptic coma. Each of these types of alterations of consciousness has a specific semiology and a distinct pathophysiologic mechanism. In this proposal we emphasize the need to clearly define each of these alterations/loss of consciousness and to apply this terminology in semiologic descriptions and classifications of epileptic seizures. The proposal is a consensus opinion of experienced epileptologists, and it is hoped that it will lead to systematic studies that will allow a scientific characterization of the different types of alterations/loss of consciousness described in this article.
EVALuna2:22297

Proposal of a rating scale to recognize Fabry disease in patients with nonspecific gastrointestinal symptoms - Hilz, Max-Josef; Arbustini, Eloisa; Dagna, Lorenzo; Gasbarrini, Antonio; Goizet, Cyril; Lacombe, Didier; Liguori, Rocco; Manna, Raffaele; Politei, Juan; Spada, Marco; Burlina, Alessandro (2018)
EVALuna2:201957

Protective Functions of Reactive Astrocytes Following Central Nervous System Insult - Linnerbauer, Mathias; Rothhammer, Veit (Frontiers in Immunology, 2020)
Astrocytes play important roles in numerous central nervous system disorders including autoimmune inflammatory, hypoxic, and degenerative diseases such as Multiple Sclerosis, ischemic stroke, and Alzheimer’s disease. Depending on the spatial and temporal context, activated astrocytes may contribute to the pathogenesis, progression, and recovery of disease. Recent progress in the dissection of transcriptional responses to varying forms of central nervous system insult has shed light on the mechanisms that govern the complexity of reactive astrocyte functions. While a large body of research focuses on the pathogenic effects of reactive astrocytes, little is known about how they limit inflammation and contribute to tissue regeneration. However, these protective astrocyte pathways might be of relevance for the understanding of the underlying pathology in disease and may lead to novel targeted approaches to treat autoimmune inflammatory and degenerative disorders of the central nervous system. In this review article, we have revisited the emerging concept of protective astrocyte functions and discuss their role in the recovery from inflammatory and ischemic disease as well as their role in degenerative disorders. Focusing on soluble astrocyte derived mediators, we aggregate the existing knowledge on astrocyte functions in the maintenance of homeostasis as well as their reparative and tissue-protective function after acute lesions and in neurodegenerative disorders. Finally, we give an outlook of how these mediators may guide future therapeutic strategies to tackle yet untreatable disorders of the central nervous system.
CRIS-Team Scopus Importer:2020-10-30
Keywords: Alzheimer’s disease; astrocytes; astrogliosis; ischemic stroke; multiple sclerosis; neurodegeneration; neuroinflammation; protective

Protective mucosal immunity against SARS-CoV-2 after heterologous systemic RNA-mucosal adenoviral vector immunization - Lapuente, Dennis; Fuchs, Julian; Willar, J.; Antao, A.; Eberlein, V.; Uhlig, N.; Issmail, L.; Schmidt, Anna; Oltmanns, Friederike; Peter, Anne; Müller-Schmucker, Sandra; Irrgang, P.; et al. (EUROPEAN JOURNAL OF IMMUNOLOGY, 2022)
CRIS-Team WoS Importer:2023-01-27

Proteolysis of CD44 at the cell surface controls a downstream protease network - Woehner, Birte; Li, Wenjia; Hey, Sven; Drobny, Alice; Werny, Ludwig; Becker-Pauly, Christoph; Lucius, Ralph; Zunke, Friederike; Linder, Stefan; Arnold, Philipp (Frontiers in Molecular Biosciences, 2023)
The cell surface receptor cluster of differentiation 44 (CD44) is the main hyaluronan receptor of the human body. At the cell surface, it can be proteolytically processed by different proteases and was shown to interact with different matrix metalloproteinases. Upon proteolytic processing of CD44 and generation of a C-terminal fragment (CTF), an intracellular domain (ICD) is released after intramembranous cleavage by the γ-secretase complex. This intracellular domain then translocates to the nucleus and induces transcriptional activation of target genes. In the past CD44 was identified as a risk gene for different tumor entities and a switch in CD44 isoform expression towards isoform CD44s associates with epithelial to mesenchymal transition (EMT) and cancer cell invasion. Here, we introduce meprin β as a new sheddase of CD44 and use a CRISPR/Cas9 approach to deplete CD44 and its sheddases ADAM10 and MMP14 in HeLa cells. We here identify a regulatory loop at the transcriptional level between ADAM10, CD44, MMP14 and MMP2. We show that this interplay is not only present in our cell model, but also across different human tissues as deduced from GTEx (Gene Tissue Expression) data. Furthermore, we identify a close relation between CD44 and MMP14 that is also reflected in functional assays for cell proliferation, spheroid formation, migration and adhesion.
CRIS-Team Scopus Importer:2023-03-24
Keywords: ADAM10; CD44; cell adhesion; meprin β; MMP14; MMP2; shedding; tumor spheroid

Psychiatric Presentation of Anti-NMDA Receptor Encephalitis - Endres, Dominique; Rauer, Sebastian; Kern, Winfried; Venhoff, Nils; Maier, Simon J.; Runge, Kimon; Süß, Patrick; Feige, Bernd; Nickel, Kathrin; Heidt, Timo; Domschke, Katharina; Egger, Karl; et al. (Frontiers in Neurology, 2019)
Background: Anti-N-methyl D-aspartate (NMDA) receptor encephalitis is an autoimmune condition characterized by neuropsychiatric symptoms, including epileptic seizures, movement disorders, autonomic instability, disturbances of consciousness, paranoia, delusions, and catatonia. Ovarian teratomas and viral infections, typically Herpes simplex viruses, have previously been demonstrated to precipitate anti-NMDA receptor encephalitis, but in many cases, the trigger remains unclear. The detection of anti-NMDA receptor antibodies in cerebrospinal fluid (CSF), in combination with other CSF, electroencephalography (EEG), or magnetic resonance imaging (MRI) abnormalities, typically leads to diagnostic clarification. Case Presentation: We present the case of a 22-year-old female patient who developed an acute polymorphic psychotic episode 3 days after receiving a booster vaccination against tetanus, diphtheria, pertussis, and polio (Tdap-IPV). Her psychiatric symptoms were initially diagnosed as a primary psychiatric disorder. Her MRI, EEG, and CSF results were non-specific. Anti-NMDA receptor IgG antibodies against the GluN1 subunit were detected in her serum (with a maximum titer of 1:320), but not in her CSF. [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) showed pronounced relative hypermetabolism of her association cortices and a relative hypometabolism of the primary cortices, on the basis of which an anti-NMDA receptor encephalitis diagnosis was made, and treatment with a steroid pulse was initiated. The treatment led to fast and convincing clinical improvement with normalization of neuropsychological findings, considerable improvement of FDG-PET findings, and decreasing antibody titers. Conclusion: The patient's psychiatric symptoms were most likely caused by anti-NMDA receptor encephalitis. Her polymorphic psychotic symptoms first occurred after she had received a Tdap-IPV booster vaccination. Although the vaccination cannot have caused the initial antibody formation since IgG serum antibodies were detected only 3 days after administration of the vaccine, the vaccine may have exerted immunomodulatory effects. MRI, EEG, and CSF findings were non-specific; however, FDG-PET identified brain involvement consistent with anti-NMDA receptor encephalitis. This case shows the importance of implementing a multimodal diagnostic work-up in similar situations. The negative CSF antibody finding furthermore fits to the hypothesis that the brain may act as an immunoprecipitator for anti-NMDA receptor antibodies.
CRIS-Team Scopus Importer:2019-12-03
Keywords: anti-NMDA receptor encephalitis; antibodies; autoimmune psychosis; encephalopathy; steroids; vaccination

Psychische Verfassung nicht behinderter MS-Patienten - Tallner, Alexander; Waschbisch, Anne; Hentschke, Christian; Pfeifer, Klaus; Mäurer, Mathias (Der Nervenarzt, 2009)

Psychogenic nonepileptic seizures: clinical characteristics and outcome - Volbers, Bastian; Walther, Katrin; Kurzbuch, Katrin; Erdmann, Laura; Gollwitzer, Stephanie; Lang, Johannes; Onugoren, Muejgan Dogan; Schwarz, Michael; Schwab, Stefan; Hamer, Hajo (Brain and Behavior, 2022)
Background: Clinical characteristics, outpatient situation, and outcome in patients with psychogenic nonepileptic seizures (PNES) remain to be elucidated. Methods: Patients diagnosed with PNES after video-electroencephalography (EEG) monitoring (VEM) 03/2000–01/2016 at the Erlangen Epilepsy Center were surveyed between June 2016 and February 2017. Primary outcome was PNES cessation defined as no PNES episodes within > = 12 months prior to the interview. Secondary outcome variables included quality of life (QoL) and dependency. Sensitivity analysis included patients with proven PNES during VEM without comorbid epilepsy. Results: Ninety-nine patients were included (median age 38 (interquartile range (IQR 29–52)) years; 68 (69%) females, follow-up 4 (IQR 2.1–7.7) years). Twenty-eight (28%) patients suffered from comorbid epilepsy. Twenty-five (25%) patients reported PNES cessation. Older age at symptom onset (odds ratio (OR) related to PNES cessation: 0.95 (95% CI 0.90–0.99)), comorbid epilepsy (OR 0.16 (95% CI 0.03–0.83)), anxiety disorder (OR 0.15 (95% CI 0.04–0.61)), and tongue biting (OR 0.22 (95% CI 0.03–0.91)) remained independently associated with ongoing PNES activity after adjustment. Sensitivity analysis (n = 63) revealed depressive disorder (OR 0.03 (95% CI 0.003–0.34)) instead of anxiety as independent predictor, while this seemed relevant only in patients older than 26 years at onset (OR 0.04 (95% CI 0.002–0.78) versus OR 0.21 (95% CI 0.02–1.84) in patients younger than 26 years). PNES cessation was associated with increased median QoL (8 (IQR 7–9) versus 5.5 (IQR 4–7); p <.001) and an increased frequency of financial independency (14 (56%) versus 21 (28%); p =.01). Conclusions: We found poor outcomes in PNES especially in older patients at onset with comorbid depressive disorder. Comorbid epilepsy also seems to be a major risk factor of ongoing PNES activity, which in turn affects patients’ daily living.
CRIS-Team Scopus Importer:2022-04-22
Keywords: activities of daily living; mental disorders; nonepileptic seizures; patient-relevant outcome; prognosis

Psychological distress after subarachnoid hemorrhage: patient support groups can help us better detect it - Noble, Adam J.; Schenk, Thomas (Journal of the Neurological Sciences, 2014)
One-quarter of subarachnoid hemorrhage (SAH) survivors develop psychological distress. This impedes recovery. Limitations to existing care pathways mean that distress often goes undetected. We need to know how to better identify it.Support groups for SAH exist in many countries. No research has been conducted on them. Distressed patients might be concentrated amongst them. If true, this could offer a low-cost way to help better identify distress. We conducted the first study to determine which survivors access such groups, their needs and compared them to the wider SAH population.414 UK SAH survivors affiliated with national support groups were recruited. They completed a questionnaire, including validated measures of anxiety, depression and posttraumatic stress, and asked whether they had been examined or treated for distress post-SAH. Regression established factors associated with treatment.Participants' mean age at SAH was 44.6 and 312 (75%) were female. Most (68.4%) reported a cerebral aneurysm as their SAH's cause and were treated with coiling. Median years since SAH were three. Over three-quarters of participants were experiencing clinical distress. Regression found distressed participants were twice as likely to have been examined and treated for distress. Nevertheless, 47% of distressed participants had not been examined for distress post-SAH and 55% had not been offered treatment.Psychological distress is overrepresented amongst support groups. Members also tend to be younger and female. Establishing referral pathways from support groups to health-systems might improve detection of distress and allow the benefits of improved survival from SAH to be fully realized.
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Psychological long-term outcome in patients with psychogenic nonepileptic seizures - Walther, Katrin; Volbers, Bastian; Erdmann, Laura; Onugoren, Muejgan Dogan; Gollwitzer, Stephanie; Kasper, Burkhard; Kurzbuch, Katrin; Lang, Johannes; Schwab, Stefan; Schwarz, Michael; Hamer, Hajo (Epilepsia, 2019)
Objective To examine the long-term outcome of psychological status, personality, and health-related quality of life (HRQoL) in patients with psychogenic nonepileptic seizures (PNES) and to define predictors of favorable outcome of cessation of PNES. Method Patients diagnosed with PNES during video-electroencephalography (EEG) monitoring at the Erlangen Epilepsy Center were contacted 1-16 years after communicating the diagnosis. Follow-up information from each participant was obtained by interview (PNES outcome) and by self-reported questionnaires of psychological symptoms (Beck Depression Inventory-II, Symptom Checklist-90-Standard, Dissociative Symptoms questionnaire), personality traits (Freiburg Personality Inventory-Revised), and HRQoL (36-Item Short Form Health Survey). Results Fifty-two patients participated in the study (mean age +/- standard deviation [SD] 40.5 +/- 14.0 years; 75% female, follow-up: 5.3 +/- 4.2 years). Nineteen patients (37%) were free of PNES for the past 12 months. Patients with persisting PNES were older at disease onset (32.9 vs 22.3 years, P < 0.01) and diagnosis (40.5 vs 27.2 years, P < 0.001), and showed worse psychological functioning, lower extraversion and life satisfaction, and higher inhibitedness and worse HRQoL than PNES-free patients. Patients with cessation of PNES were within the normal range in all dimensions. Cessation of PNES was best predicted by younger age at PNES onset and higher extraversion. Significance Outcome of PNES is poor, psychopathology is high, and HRQoL is low in patients with persistent PNES but may normalize with PNES cessation. High introversion and older age at PNES onset are risk factors for persistent PNES.
CRIS-Team WoS Importer:2019-04-16

Psychosocial long-term outcome in patients with psychogenic non-epileptic seizures - Walther, Katrin; Volbers, Bastian; Erdmann, Laura; Kurzbuch, Katrin; Lang, Johannes; Müller, Tamara; Reindl, Caroline; Schwarz, Michael; Schwab, Stefan; Hamer, Hajo (Seizure-European Journal of Epilepsy, 2020)
Purpose: To evaluate psychosocial long-term outcome in patients diagnosed with psychogenic nonepileptic seizures (PNES) and to predict outcome of PNES, economic status, and quality of life (QoL) at follow-up. Methods: Patients diagnosed with PNES in the video-EEG-monitoring unit at our Epilepsy center between 2002–2016 were contacted by phone 1–16 years after communicating the diagnosis. Patients underwent a structured interview asking for current PNES status, psychosocial situation (economic status, marital status, setting of living, driving), depression, and QoL. Results: Of 70 PNES patients without comorbid epilepsy (age: 41.1 ± 13.5 years; 74 % female, follow-up: 5.2 ± 4.2 years), 23 patients (33 %) reported to be free of PNES during the last 12 months. Patients with cessation of PNES were younger at PNES onset (p < .01) and diagnosis (p < .01) and had a higher education (p < .05). At follow-up, the proportion of economically active patients only increased in individuals with cessation of PNES (p < .001) while an increased number of patients with persisting PNES relied on governmental support (p < .001). Cessation of PNES was associated with better mood (p < .01) and QoL (p < .001). In multiple regression models, cessation of PNES was only predicted by younger age at onset, while good economic outcome was determined by younger age and good economic status at diagnosis and cessation of PNES at follow-up. Good QoL at follow-up was predicted by low depressive symptoms, freedom of PNES, and economic activity at follow-up. Conclusion: Long-term outcome in patients with PNES remains to be poor and the majority of patients continue to have PNES. Cessation of PNES was associated with good economic outcome, mood, and QoL.
CRIS-Team Scopus Importer:2020-11-27
Keywords: Employment; Long-term outcome; Marital status; Mood; Psychogenic non-epileptic seizures; Quality of life

Psychosocial outcome in epilepsy after extratemporal surgery - Walther, Katrin; Onugoren, Muejgan Dogan; Buchfelder, Michael; Gollwitzer, Stephanie; Graf, Wolfgang; Kasper, Burkhard; Kriwy, Peter; Kurzbuch, Katrin; Lang, Johannes; Roessler, Karl; Schwab, Stefan; Schwarz, Michael; et al. (Epilepsy and Behavior, 2018)
OBJECTIVE: Only limited data exist on psychosocial long-term outcome after epilepsy surgery in patients with extratemporal epilepsy. The aim of this study was to investigate psychosocial outcome after extratemporal epilepsy surgery and to assess factors predicting favorable outcome. METHOD: Sixty-five out of 104 eligible patients who had undergone extratemporal epilepsy surgery at our epilepsy center between 1990 and 2015 (mean age: 42.2. years; 75% of the resections in the frontal lobe) completed a questionnaire asking about seizure status, employment status, marital and living situation, driving status, depressive symptoms, and quality of life (QOL). Follow-up was on average 9.2years after surgery (range: 1-26years). RESULTS: Thirty-eight (58%) patients were free of disabling seizures (Engel class I), and 28 (43%) have not experienced any seizures after surgery (Engel class IA). Employment rate in the primary labor market remained at 45%, but more patients lost employment (14%) than gained employment (8%). Postoperative employment was predicted by preoperative employment (p=.007), seizure freedom (p=.025), older age at seizure onset (p=.018), younger age at follow-up (p=.035), and female gender (p=.048). Seizure-free patients were more likely to be driving; have a partner, particularly in males; and have lower depressive scores. Quality of life at follow-up was best predicted by employment (p=.012), partnership (p=.025), and seizure freedom (p=.025). In contrast, recurrence of seizures and early seizure onset were associated with poor psychosocial outcome, particularly in men. CONCLUSION: The study provides support that extratemporal surgery can lead to improved QOL and favorable psychosocial outcome. Seizure freedom is important but not the only determinant of good psychosocial outcome.
EVALuna2:35520

Publisher Correction: Nfat/calcineurin signaling promotes oligodendrocyte differentiation and myelination by transcription factor network tuning - Weider, Matthias; Starost, Laura Julia; Groll, Katharina; Küspert, Melanie; Sock, Elisabeth; Wedel, Miriam; Fröb, Franziska; Schmitt, Christian; Baroti, Tina; Hartwig, Anna; Hillgärtner, Simone; Piefke, Sandra; et al. (Nature Communications, 2018)
The originally published version of this Article omitted Tanja Kuhlmann and Michael Wegner as jointly supervising authors. This has now been corrected in both the PDF and HTML versions of the Article.
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Pull Test Estimation in Parkinson's Disease Patients using Wearable Sensor Technology - Pasluosta, Cristian Federico; Barth, Jens; Gaßner, Heiko; Klucken, Jochen; Eskofier, Björn (37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society EMBC ’15, 2015)

Pupillometry in the follow-up of patients undergoing EVT - prediction of space-occupying hemispheric infarction - Kossel, Clara-Sophie; Kobus, Franca; Borutta, Matthias; Kärtner, Maximilian; Kuramatsu, Joji; Engelhorn, Tobias; Schwab, Stefan; Köhn, Julia (Journal of Neurology, 2023)
Background: Despite benefits of endovascular treatment (EVT) for large vessel occlusion (LVO) ischemic stroke, space-occupying brain edema (BE) represents a detrimental complication. In critical-care settings, CT-imaging is needed for monitoring these patients. Yet, bed-side techniques with the potential to predict whether patients develop BE or not would facilitate a time- and cost-efficient patient care. We assessed clinical significance of automated pupillometry in the follow-up of patients undergoing EVT. Methods: From 10/2018 to 10/2021, neurocritical-care-unit patients were retrospectively enrolled after EVT of anterior circulation LVO. We monitored parameters of pupillary reactivity [light-reflex-latency (Lat), constriction- and redilation-velocities (CV, DV), percentage-change-of-apertures (per-change); NeurOptics-pupilometer®] up to every hour on day 1–3 of ICU stay. BE was defined as midline shift ≥ 5 mm on follow-up imaging 3–5 days after EVT. We calculated mean values of intra-individual differences between successive pairs of parameters (mean-deltas), determined best discriminative cut-off values for BE development (ROC-analyses), and evaluated prognostic performance of pupillometry for BE development (sensitivity/specificity/positive-/negative-predictive-values). Results: 3241 pupillary assessments of 122 patients [67 women, 73 years (61.0–85.0)] were included. 13/122 patients developed BE. Patients with BE had significantly lower CVs, DVs, and smaller per-changes than patients without BE. On day 1 after EVT mean-deltas of CV, DV, and per-changes were significantly lower in patients with than without BE. Positive-predictive-values of calculated thresholds to discriminate both groups were considerably low, yet, we found high negative-predictive-values for CV, DV, per-changes, and mean-deltas (max.: 98.4%). Conclusion: Our data suggest associations between noninvasively detected changes in pupillary reactivity and BE early after LVO-EVT. Pupillometry may identify patients who are unlikely to develop BE and may not need repetitive follow-up-imaging or rescue-therapy.
CRIS-Team Scopus Importer:2023-06-30
Keywords: Automated pupillometry; Endovascular treatment; Ischemic stroke; Large vessel occlusion; Pupillary reactivity

Quality of life and correlating factors in children, adolescents with epilepsy, and their caregivers: A cross-sectional multicenter study from Germany - Riechmann, Janna; Willems, Laurent M.; Boor, Rainer; Kieslich, Matthias; Knake, Susanne; Langner, Cornelia; Neubauer, Bernd A.; Oberman, Bettina; Philippi, Heike; Reese, Jens P.; Rochel, Michael; Schubert-Bast, Susanne; et al. (Seizure-European Journal of Epilepsy, 2019)
Purpose: To identify factors correlating with poorer quality of life (QoL) in children and adolescents with epilepsy and regarding QoL and depression of their caregivers in Germany. Method: A cross-sectional multicenter study on QoL and depression was performed in two representative German states (Hessen and Schleswig-Holstein). Variance analysis, linear regression, and bivariate correlation were used to identify correlating factors for poorer QoL and symptoms of depression. Results: Data from 489 children and adolescents (mean age 10.4 ± 4.2 years, range 0.5–17.8; 54.0% male) and their caregivers were collected. We identified missing seizure freedom (p = 0.046), concomitant diseases (p = 0.007), hospitalization (p = 0.049), recent status epilepticus (p = 0.035), living in a nursing home or with foster parents (p = 0.049), and relevant degree of disability (p = 0.007) to correlate with poorer QoL in children and adolescents with epilepsy. Poorer QoL of caregivers was associated with longer disease duration (p = 0.004), non-idiopathic (mainly structural-metabolic) epilepsy (p = 0.003), ongoing seizures (p = 0.003), concomitant diseases (p = 0.003), relevant disability (p = 0.003), or status epilepticus (p = 0.003) as well as with unemployment of the primary caretaker (p = 0.010). Symptoms of depression of caregivers were associated with non-idiopathic epilepsy (p = 0.003), concomitant diseases (p = 0.003), missing seizure freedom (p = 0.007), status epilepticus (p = 0.004), or a relevant disability (p = 0.004) of their ward. A poorer QoL value of the children and adolescents correlated with a poorer QoL value of the caregivers (p < 0.001). Conclusions: Epilepsy shows a considerable impact on QoL and symptoms of depression. Early and effective therapy should focus on reduction of seizure frequency and the probability for developing status epilepticus. Furthermore, comprehensive care should pay attention at comorbidities, consequences of disability and dependency on others.
CRIS-Team Scopus Importer:2019-05-02
Keywords: Anticonvulsants; Antiepileptic drug; Depression; Seizure; Status epilepticus

Quantifying postural instability in Parkinsonian gait from inertial sensor data during standardised clinical gait tests - Hannink, Julius; Kluge, Felix; Gaßner, Heiko; Klucken, Jochen; Eskofier, Björn (2017 IEEE 14th International Conference on Wearable and Implantable Body Sensor Networks (BSN), 2017)

Quantitative 1H and 23Na muscle MRI in Facioscapulohumeral muscular dystrophy patients - Gerhalter, Teresa; Marty, Benjamin; Gast, Lena; Porzelt, Katharina; Heiß, Rafael; Uder, Michael; Schwab, Stefan; Carlier, Pierre G.; Nagel, Armin Michael; Türk, Matthias (Journal of Neurology, 2020)
Objective: Our aim was to assess the role of quantitative 1H and 23Na MRI methods in providing imaging biomarkers of disease activity and severity in patients with Facioscapulohumeral muscular dystrophy (FSHD). Methods: We imaged the lower leg muscles of 19 FSHD patients and 12 controls with a multimodal MRI protocol to obtain STIR-T2w images, fat fraction (FF), water T2 (wT2), water T1 (wT1), tissue sodium concentration (TSC), and intracellular-weighted sodium signal (inversion recovery (IR) and triple quantum filter (TQF) sequence). In addition, the FSHD patients underwent muscle strength testing. Results: Imaging biomarkers related with water mobility (wT1 and wT2) and ion homeostasis (TSC, IR, TQF) were increased in muscles of FSHD patients. Muscle groups with FF > 10% had higher wT2, wT1, TSC, IR, and TQF values than muscles with FF < 10%. Muscles with FF < 10% resembled muscles of healthy controls for these MRI disease activity measures. However, wT1 was increased in few muscles without fat replacement. Furthermore, few STIR-negative muscles (n = 11/76) exhibited increased wT1, TSC, IR or TQF. Increased wT1 as well as 23Na signals were also present in muscles with normal wT2. Muscle strength was related to the mean FF and all imaging biomarkers of tibialis anterior except wT2 were correlated with dorsal flexion. Conclusion: The newly evaluated imaging biomarkers related with water mobility (wT1) and ion homeostasis (TSC, IR, TQF) showed different patterns compared to the established markers like FF in muscles of FSHD patients. These quantitative biomarkers could thus contain valuable complementary information for the early characterization of disease progression.
CRIS-Team Scopus Importer:2020-10-23
Keywords: Facioscapulohumeral muscular dystrophy; Quantitative MRI; Sodium MRI; Triple quantum filter; Water T

Quantitative 7T sodium magnetic resonance imaging of the human brain using a 32-channel phased-array head coil: Application to patients with secondary progressive multiple sclerosis - Wilferth, Tobias; Mennecke, Angelika; Gast, Lena; Lachner, Sebastian; Müller, Max; Rothhammer, Veit; Huhn, Konstantin; Uder, Michael; Dörfler, Arnd; Nagel, Armin Michael; Schmidt, Manuel (NMR in Biomedicine, 2022)
Apparent tissue sodium concentrations (aTSCs) determined by 23Na brain magnetic resonance imaging (MRI) have the potential to serve as a biomarker in pathologies such as multiple sclerosis (MS). However, the quantification is hindered by the intrinsically low signal-to-noise ratio of 23Na MRI. The purpose of this study was to improve the accuracy and reliability of quantitative 23Na brain MRI by implementing a dedicated postprocessing pipeline and to evaluate the applicability of the developed approach for the examination of MS patients. 23Na brain MRI measurements of 13 healthy volunteers and 17 patients with secondary progressive multiple sclerosis (SPMS) were performed at 7 T using a dual-tuned 23Na/1H birdcage coil with a receive-only 32-channel phased array. The aTSC values were determined for normal appearing white matter (NAWM) and normal appearing gray matter (NAGM) in healthy subjects and SPMS patients. Signal intensities were normalized using the mean cerebrospinal fluid (CSF) sodium concentration determined in 37 separate patients receiving a spinal tap for routine diagnostic purposes. Five volunteers underwent MRI examinations three times in a row to assess repeatability. Coefficients of variation (CoVs) were used to quantify the repeatability of the proposed method. aTSC values were compared regarding brain regions and subject cohort using the paired-samples Wilcoxon rank-sum test. Laboratory CSF sodium concentration did not differ significantly between patients without and with MS (p = 0.42). The proposed quantification workflow for 23Na MRI was highly repeatable with CoVs averaged over all five volunteers of 1.9% ± 0.9% for NAWM and 2.2% ± 1.6% for NAGM. Average NAWM aTSC was significantly higher in patients with SPMS compared with the control group (p = 0.009). Average NAGM aTSC did not differ significantly between healthy volunteers and MS patients (p = 0.98). The proposed postprocessing pipeline shows high repeatability and the results can serve as a baseline for further studies establishing 23Na brain MRI as a biomarker in diseases such as MS.
CRIS-Team Scopus Importer:2022-08-19
Keywords: 7 T; brain MRI; multiple sclerosis

Quantitative Corticospinal Tract Assessment in Acute Intracerebral Hemorrhage - Volbers, Bastian; Mennecke, Angelika; Kästle, Nicola; Huttner, Hagen; Schwab, Stefan; Schmidt, Manuel; Engelhorn, Tobias Martin; Dörfler, Arnd (Translational Stroke Research, 2020)
Intracerebral hemorrhage (ICH) prognostication during the acute phase is often subjective among physicians and often affects treatment decisions. The present study explores objective imaging parameters using quantitative corticospinal tract (CST) fiber reconstruction during the acute phase of ICH and correlates these parameters with functional outcome and patient recovery. We prospectively enrolled nonsurgical spontaneous supratentorial ICH patients and obtained an MRI scan on day 5 ± 1. Q-space diffeomorphic reconstruction was performed using DSI Studio, and quantitative anisotropy (QA) was calculated. The CST was reconstructed based on QA. The dichotomized modified Rankin Scale score on day 90 (favorable outcome = 0–2) and Barthel Index (favorable recovery = 100 on day 90 or improvement between discharge and day 90 > 60%) were assessed. Thirty-three patients, median age 72 years (interquartile range (IQR) 64–83), 21 female (64%), 21 (64%) with lobar hemorrhage, median ICH volume on admission 15.0 (IQR 7.0–27.4) mL, were included. Sixteen patients (48%) had a favorable outcome and 24 (73%) had a favorable recovery. The mean number of ipsilesional reconstructed CST fiber pathways was higher in patients with favorable outcomes (153 (standard deviation (SD) 103) vs. 60 (SD 39), p = 0.003) and predicted outcome after adjustment (Exp(B) = 1.016 (95% CI = 1.002–1.030)). QA in the ipsilesional posterior limb of the internal capsule showed a trend towards an association with favorable outcome (Exp(B) = 1.194 (95% CI = 0.991–1.439 (adjusted))). The total (ipsilesional + contralesional) number of reconstructed fiber pathways was associated with favorable recovery (Exp(B) = 1.025 (95% CI = 1.003–1.047 (adjusted))). Quantitative tractography parameters assessed in the acute phase of ICH may represent a promising predictor of long-term outcome and recovery. This might facilitate prognostic evaluation and organization of rehabilitation.
CRIS-Team Scopus Importer:2020-10-02
Keywords: All rehabilitation; DWI; Intracerebral hemorrhage; MRI; Outcome research

Quantitative EEG After Subarachnoid Hemorrhage Predicts Long-Term Functional Outcome - Gollwitzer, Stephanie; Müller, Tamara; Hopfengärtner, Rüdiger; Rampp, Stephan; Merkel, Jasmin; Hagge, Mareike; Jukic, Jelena; Lang, Johannes; Madžar, Dominik; Onugoren, Müjgan Dogan; Huttner, Hagen; Schwab, Stefan; et al. (Journal of Clinical Neurophysiology, 2019)
PURPOSE: Delayed cerebral ischemia is a major complication after subarachnoid hemorrhage. Our previous study showed that alpha power reduction in continuous quantitative EEG predicts delayed cerebral ischemia. In this prospective cohort, we aimed to determine the prognostic value of alpha power in quantitative EEG for the long-term outcome of patients with subarachnoid hemorrhage. METHODS: Adult patients with nontraumatic subarachnoid hemorrhage were included if admitted early enough for EEG to start within 72 hours after symptom onset. Continuous six-channel EEG was applied. Unselected EEG signals underwent automated artifact rejection, power spectral analysis, and detrending. Alpha power decline of ≥40% for ≥5 hours was defined as critical EEG event based on previous findings. Six-month outcome was obtained using the modified Rankin scale. RESULTS: Twenty-two patients were included (14 male; mean age, 59 years; Hunt and Hess grade I-IV; duration of EEG monitoring, median 14 days). Poor outcome (modified Rankin scale, 2-5) was noted in 11 of 16 patients (69%) with critical EEG events. All six patients (100%) without EEG events achieved an excellent outcome (modified Rankin scale 0, 1) (P = 0.0062; sensitivity 100%, specificity 54.5%). Vasospasm detected with transcranial Doppler/Duplex sonography appeared 1.5 days after EEG events and showed weaker association with outcome (P = 0.035; sensitivity 100%, specificity 45.5%). There was no significant association between EEG events and ischemic lesions on imaging (P = 0.1). Also, no association between ischemic lesions and outcome was seen (P = 0.64). CONCLUSIONS: Stable alpha power in quantitative EEG reflects successful therapy and predicts good functional outcome after subarachnoid hemorrhage. Critical alpha power reduction indicates an increased risk of poor functional outcome.
CRIS-Team Scopus Importer:2019-05-03

Quantitative EEG may predict weaning failure in ventilated patients on the neurological intensive care unit - Welte, Tamara; Gabriel, Maria; Hopfengaertner, Ruediger; Rampp, Stefan; Gollwitzer, Stephanie; Lang, Johannes; Stritzelberger, Jenny; Reindl, Caroline; Madzar, Dominik; Sprügel, Maximilian; Huttner, Hagen; Kuramatsu, Joji; et al. (Scientific Reports, 2022)
Neurocritical patients suffer from a substantial risk of extubation failure. The aim of this prospective study was to analyze if quantitative EEG (qEEG) monitoring is able to predict successful extubation in these patients. We analyzed EEG-monitoring for at least six hours before extubation in patients receiving mechanical ventilation (MV) on our neurological intensive care unit (NICU) between November 2017 and May 2019. Patients were divided in 2 groups: patients with successful extubation (SE) versus patients with complications after MV withdrawal (failed extubation; FE), including reintubation, need for non-invasive ventilation (NIV) or death. Bipolar six channel EEG was applied. Unselected raw EEG signal underwent automated artefact rejection and Short Time Fast Fourier Transformation. The following relative proportions of global EEG spectrum were analyzed: relative beta (RB), alpha (RA), theta (RT), delta (RD) as well as the alpha delta ratio (ADR). Coefficient of variation (CV) was calculated as a measure of fluctuations in the different power bands. Mann–Whitney U test and logistic regression were applied to analyze group differences. 52 patients were included (26 male, mean age 65 ± 17 years, diagnosis: 40% seizures/status epilepticus, 37% ischemia, 13% intracranial hemorrhage, 10% others). Successful extubation was possible in 40 patients (77%), reintubation was necessary in 6 patients (12%), 5 patients (10%) required NIV, one patient died. In contrast to FE patients, SE patients showed more stable EEG power values (lower CV) considering all EEG channels (RB: p < 0.0005; RA: p = 0.045; RT: p = 0.045) with RB as an independent predictor of weaning success in logistic regression (p = 0.004). The proportion of the EEG frequency bands (RB, RA RT, RD) of the entire EEG power spectrum was not significantly different between SE and FE patients. Higher fluctuations in qEEG frequency bands, reflecting greater fluctuation in alertness, during the hours before cessation of MV were associated with a higher rate of complications after extubation in this cohort. The stability of qEEG power values may represent a non-invasive, examiner-independent parameter to facilitate weaning assessment in neurocritical patients.
CRIS-Team Scopus Importer:2022-05-20

Quantitative sensory phenotyping in chronic neuropathic pain patients treated with unilateral L4-dorsal root ganglion stimulation - Kinfe, Thomas Mehari; von Willebrand, Nico; Stadlbauer, Andreas; Buchfelder, Michael; Yearwood, Thomas L.; Muhammad, Sajjad; Chaudhry, Shafqat R.; Gravius, Sascha; Randau, Thomas; Winder, Klemens; Maihöfner, Christian; Gravius, Nadine; et al. (Journal of Translational Medicine, 2020)
Background: In a previous study, we reported that selective dorsal root ganglion stimulation (DRGSTIM) at DRG level L4 promoted a favorable outcome for complex regional pain syndrome (CRPS) patients along with DRGSTIM-related changes of inflammatory biomarkers in blood and saliva. The impact on somatosensation is largely unknown. Herein, we assessed the quantitative sensory profile to quantify L4-DRGSTIM effects in CRPS patients. Methods: Twelve refractory CRPS patients (4 female; 8 male; mean age 69 ± 9 years) received standardized quantitative sensory testing (QST) protocol at baseline and after 3 months of unilateral L4-DRGSTIM assessing nociceptive and non-nociceptive thermal and mechanical sensitivity of the knee affected by CRPS and the contralateral non-painful knee area. Results: At baseline, CRPS subjects showed significantly increased thresholds for warmth, tactile and vibration detection (WDT, MDT and VDT) and exaggerated pain summation (WUR). After 3 months of unilateral L4-DRGSTIM all pain parameters exhibited trends towards normalization of sensitivity accumulating to a significant overall normalization for pain sensitivity (effect size: 0.91, p < 0.01), while with the one exception of WDT all non-nociceptive QST parameters remained unchanged. Overall change of non-nociceptive detection was negligible (effect size: 0.25, p > 0.40). Notably, reduction of pain summation (WUR) correlated significantly with pain reduction after 3 months of L4-DRGSTIM. Conclusions: Selective L4-DRGSTIM lowered ongoing pain in CRPS patients and evoked significant normalization in the pain domain of the somatosensory profile. Thermoreception and mechanoreception remained unchanged. However, larger randomized, sham-controlled trials are highly warranted to shed more light on effects and mechanisms of dorsal root ganglion stimulation on quantitative sensory characteristics. The study protocol was registered at the 15.11.2016 on German Register for Clinical Trials (DRKS ID 00011267). https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011267.
CRIS-Team Scopus Importer:2020-10-30
Keywords: Complex regional pain syndrome; Dorsal root ganglion stimulation; Objective measures for neurostimulation; Sensory quantitative testing

Quantitative susceptibility mapping depicts severe myelin deficit and iron deposition in a transgenic model of multiple system atrophy - Lambrecht, Vera; Hanspach, Jannis; Hoffmann, Alana; Seyler, Lisa; Mennecke, Angelika; Straub, Sina; Marxreiter, Franz; Bäuerle, Tobias; Winkler, Jürgen; Laun, Frederik Bernd (Experimental Neurology, 2020)
Despite internationally established diagnostic criteria, multiple system atrophy (MSA) is frequently misdiagnosed, particularly at disease onset. While neuropathological changes such as demyelination and iron deposition are typically detected in MSA, these structural hallmarks were so far only demonstrated post-mortem. Here, we examine whether myelin deficit observed in a transgenic murine model of MSA can be visualized and quantified in vivo using specific magnetic resonance imaging (MRI) approaches. Reduced myelin content was measured histologically in prototypical white matter as well as mixed grey-white matter regions i.e. corpus callosum, anterior commissure, and striatum of transgenic mice overexpressing human α-synuclein under the control of the myelin basic protein promotor (MBP29-hα-syn mice). Correspondingly, in vivo quantitative susceptibility mapping (QSM) showed a strongly reduced susceptibility contrast in white matter regions and T2-weighted MR imaging revealed a significantly reduced grey-white matter contrast in MBP29-hα-syn mice. In addition, morphological analysis suggested a pronounced, white matter-specific deposition of iron in MBP29-hα-syn mice. Importantly, in vivo MRI results were matched by comprehensive structural characterization of myelin, iron, and axonal directionality. Taken together, our results provide strong evidence that QSM is a very sensitive tool measuring changes in myelin density in conjunction with iron deposition in MBP29-hα-syn mice. This multimodal neuroimaging approach may pave the way towards a novel non-invasive technique to detect crucial neuropathological changes specifically associated with MSA.
CRIS-Team Scopus Importer:2020-04-28
Keywords: Iron; Multiple system atrophy; Myelin imaging; Quantitative susceptibility mapping; White matter

Radar-Based Tremor Quantification Using Deep Learning for Improved Parkinson’s and Palliative Care Assessment - Mejdani, Desar; Bräunig, Johanna; Grießhammer, Stefan; Krauß, Daniel; Steigleder, Tobias; Engel, Lukas; Jukic, Jelena; Rozhdestvenskaya, Anna; Winkler, Jürgen; Eskofier, Björn; Ostgathe, Christoph; Vossiek, Martin (IEEE Transactions on Radar Systems, 2024)
Tremor is one of the most prevalent movement disorders, which is especially observed in patients with Parkinson’s disease (PD) and other conditions common in palliative care (PC). Effective treatment and monitoring of disease progression are crucial in the context of PC for patients suffering from movement disorders. To this aim, accurate and continuous detection and assessment of tremor characteristics, such as the tremor frequency, is required. Current evaluations by clinicians conducted during sporadic consultations are subjective and intermittent. Radar sensors provide continuous, objective evaluations of tremor motion in patient monitoring, offering a contactless, light-independent, and privacy-preserving method that directly measures tremor’s radial motion through the Doppler effect. As previous radar-based research lacks continuous tremor monitoring in realistic scenarios, this study uses a frequency-modulated continuous-wave (FMCW) radar to detect subtle tremor motions and estimates their frequencies amid challenges such as large body motion interference in a clinical setting. Seventeen healthy participants were instructed to mimic tremors in their right hand while performing three diagnostics movements frequently used in tremor assessment, and two activities that were inspired by common daily tasks encountered in PC settings. Tremor detection and frequency estimation was enabled using suitable radar signal preprocessing followed by a neural network comprising convolutional and recurrent layers. Reference frequencies were obtained from an inertial measurement unit (IMU) attached to the participants’ right hands. Cross-validation revealed a mean absolute error (MAE) of 1.47 Hz in radar-based frequency estimation compared with the reference and a 90% accuracy in distinguishing the presence or absence of tremor, highlighting the proposed approach’s high potential for future tremor assessmen
Keywords: Sensors; Radar antennas; Palliative care; Frequency estimation; Doppler effect; Chirp; Kinetic theory; Doppler radar; Deep learning; Parkinson's disease; Deep learning; neural network; palliative care (PC); Parkinson’s disease (PD); radar; tremor

Radiopacity of intracerebral hemorrhage correlates with perihemorrhagic edema - Wagner, Irina; Volbers, Bastian; Hilz, Max-Josef; Schwab, Stefan; Staykov, Dimitre; Dörfler, Arnd (European Journal of Neurology, 2012)
Background: Experimental evidence indicates that iron plays a key role in edema formation after intracerebral hemorrhage (ICH). We investigated the relationship between ICH radiopacity on CT as a marker of hematoma iron content and perihemorrhagic edema (PHE) after ICH. Methods: We retrospectively investigated patients with spontaneous lobar and ganglionic supratentorial ICH who received follow-up CT scans during the first 7days after symptom onset (d1, d2-4, d5-7). Measurements of ICH and edema volumes were taken using a semiautomatic threshold-based volumetric algorithm. Radiopacity of the blood clot was determined using the mean Hounsfield unit (HU) count of the ICH. Results: A total of 117 patients aged 71.92±11.55years with spontaneous ICH (34.63±32.44ml) were included in the analysis. Mean ICH radiopacity was 59.7±3.4HU. We found significantly larger relative PHE at d2-4 (1.7±0.9 vs. 1.3±0.8; P=0.032) and d5-7 (2.0±1.3 vs. 1.3±0.9; P=0.007) and larger peak relative PHE (2.3±1.6 vs. 1.6±1.1; P=0.006) in patients with ICH radiopacity >60HU (n=59), as compared to patients with ICH radiopacity <60HU (n=58). Conclusions: Higher ICH radiopacity, reflecting higher in vivo hematoma iron content, is associated with more PHE after ICH. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Intracerebral hemorrhage; Perihemorrhagic edema; Radiopacity

Radiosensitivity in individuals with tuberous sclerosis complex - Kuhlmann, Lukas; Stritzelberger, Jenny; Fietkau, Rainer; Distel, Luitpold; Hamer, Hajo (Discover Oncology, 2024)
Benign tumors, but rarely cancer, are common in patients with tuberous sclerosis complex (TSC). Blood samples from patients undergoing treatment for TSC at our institution were analyzed for their individual sensitivity to ionizing radiation. Blood samples were collected from 13 adult patients with TSC. The samples were irradiated ex vivo and analyzed by 3-color fluorescence in situ hybridization. In each patient, aberrations were analyzed in 200 metaphases of chromosomes 1, 2, and 4 and scored as breaks. Radiosensitivity was determined by mean breaks per metaphase (B/M) and compared to both healthy donors and oncologic patients. The radiosensitivity (B/M) of the TSC patient cohort (n = 13; female: 46.2%, B/M: 0.48 ± 0.11) was clearly increased compared to healthy individuals of similar age (n = 90; female: 54.4%; B/M: 0.40 ± 0.09; p = 0.001). There was no difference compared to age-matched oncological patients (n = 78; female: 67.9%; B/M 0.49 ± 0.14; p = 0.246). Similarly, the proportion of radiosensitive (B/M > 0.5) and distinctly radiosensitive individuals (B/M > 0.6) was increased in the TSC and oncological patient cohorts (TSC: 30.8% and 7.7%, oncological patients: 46.2% and 14.1%) compared to the healthy individuals (11.1% and 2.2%). Although patients with TSC develop mostly benign and rarely malignant tumors, they are similarly sensitive to radiation as patients with malignant tumors.
CRIS-Team Scopus Importer:2024-10-18
Keywords: Chromosomal aberrations; In situ hybridization; Ionizing radiation; Radiosensitivity; TSC1; TSC2; Tuberous sclerosis complex

Rapid recovery of poststroke cardiac autonomic dysfunction: Causes to be considered - Wang, Ruihao; Moeller, Sebastian; Akhundova, Aynur; Marthol, Harald; Kollmar, Rainer; Köhrmann, Martin; Hilz, Max-Josef (European Journal of Neurology, 2023)
Background and purpose: Acute stroke frequently causes cardiovascular–autonomic dysfunction (CAD). Studies of CAD recovery are inconclusive, whereas poststroke arrhythmias may wane within 72 h. We evaluated whether poststroke CAD recovers within 72 h upon stroke onset in association with neurological improvement or increased use of cardiovascular medication. Methods: In 50 ischemic stroke patients (68 ± 13 years old) who—prior to hospital-admission—had no known diseases nor took medication affecting autonomic modulation, we assessed National Institutes of Health Stroke Scale (NIHSS) scores, RR intervals (RRIs), systolic and diastolic blood pressure (BP), respiration rate, parameters reflecting total autonomic modulation (RRI SD, RRI total powers), sympathetic modulation (RRI low-frequency powers, systolic BP low-frequency powers), and parasympathetic modulation (square root of mean squared differences of successive RRIs [RMSSD], RRI high-frequency powers), and baroreflex sensitivity within 24 h (Assessment 1) and 72 h after stroke onset (Assessment 2) and compared data to those of 31 healthy controls (64 ± 10 years). We correlated delta NIHSS values (Assessment 1 – Assessment 2) with delta values of autonomic parameters (Spearman rank correlation tests; significance: p < 0.05). Results: At Assessment 1, patients were not yet on vasoactive medication and had higher systolic BP, respiration rate, and heart rate, that is, lower RRIs, but lower RRI SD, RRI coefficient of variance, RRI low-frequency powers, RRI high-frequency powers, RRI total powers, RMSSDs, and baroreflex sensitivity. At Assessment 2, patients were on antihypertensives, had higher RRI SD, RRI coefficient of variance, RRI low-frequency powers, RRI high-frequency powers, RRI total powers, RMSSDs, and baroreflex sensitivity but lower systolic blood pressure and NIHSS values than at Assessment 1; values no longer differed between patients and controls except for lower RRIs and higher respiration rate in patients. Delta NIHSS scores correlated inversely with delta values of RRI SD, RRI coefficient of variance, RMSSDs, RRI low-frequency powers, RRI high-frequency powers, RRI total powers, and baroreflex sensitivity. Conclusions: In our patients, CAD recovery was almost complete within 72 h after stroke onset and correlated with neurological improvement. Most likely, early initiation of cardiovascular medication and probably attenuating stress supported rapid CAD recovery.
CRIS-Team Scopus Importer:2023-06-02
Keywords: autonomic recovery; cardiovascular autonomic dysregulation; cardiovascular medication; ischemic stroke; stroke severity

Rapid titration protocol – Experiences with a dynamic novel titration regime for vagus nerve stimulation in a group of depressive patients - Moeller, Sebastian; Wang, Ruihao; Aydin, M.; Lam, Alexandra P.; Sitter, Aileen; Grüter, J.; Philipsen, Alexandra; Müller, Helge H.O. (Journal of Clinical Neuroscience, 2019)
Vagus nerve stimulation (VNS) is an established tool in the psychiatric armamentarium for patients with therapy-resistant depression (TRD) with response rates of approximately 60%. So far, VNS is titrated slowly during ambulatory in-office visits. Thus, antidepressive effects can be expected after approximately six months. We report our experiences with a rapid dosing regime (RDR) with titration start shortly after VNS-implantation. We retrospectively analysed data of six patients with TRD who received VNS. Stimulation parameters were evaluated with regard to clinical side effects, heart rates (HR) and blood pressures (BP). Depressive symptoms were measured by Montgomery-Asberg Depression Rating Scale (MADRS) one week before and three months after implantation of the VNS. All patients received first stimulation between one and four days after surgery. We elevated output current using 0.25 mA titration steps. We increased output current between one and four days after the last titration. All patients received 1.0 mA output current after eight to 14 days post-surgery. HR and BP remained stable in all patients. All side effects were mild and temporary. MADRS scores were significantly lower three months after VNS-implantation (24 ± 8) than one week before VNS-implantation (42 ± 4; p = 0.028). The therapeutic range of VNS-parameters for antidepressive effect was reached quicker without finding increased numbers of side effects. Consequently, by using RDR the antidepressive effect of VNS-therapy for patients with TRD could be reached earlier than using slow titration. Our presented RDR might be able to significantly shorten the “clinical effect gap” due to the neurobiological and titration-related latency.
CRIS-Team Scopus Importer:2019-08-30
Keywords: Dosing; Therapy-resistant depression; TRD; Vagus nerve; Vagus nerve stimulation; VNS

Rare meets rarer: anti-synthetase syndrome in a patient with facio-scapulo-humeral muscular dystrophy - Valor-Mendez, Larissa; Manger, Bernhard; Winterholler, Martin; Schett, Georg; Tuerk, Mattias; Knitza, Johannes (Rheumatology, 2022)
CRIS-Team WoS Importer:2022-07-08

Real-Time, In Vivo Monitoring, and Quantitative Assessment of Intra-Arterial Vasospasm Therapy - Gölitz, Philipp; Kaschka, Iris; Lang, Stefan; Roessler, Karl; Knossalla, Frauke; Dörfler, Arnd (Neurocritical Care, 2016)
Our study aimed to evaluate whether the effect of an intra-arterial vasospasm therapy can be assessed quantitatively by in vivo blood flow analysis using the postprocessing algorithm parametric color coding (PCC).We evaluated 17 patients presenting with acute clinical deterioration due to vasospasm following subarachnoidal hemorrhage treated with intra-arterial nimodipine application. Pre- and post-interventional DSA series were post-processed by PCC. The relative time to maximum opacification (rTmax) was calculated in 14 arterially and venously located points of interest. From that data, the pre- and post-interventional cerebral circulation time (CirT) was calculated. Additionally, the arterial vessel diameters were measured. Pre- and post-interventional values were compared and tested for significance, respectively.Flow analysis revealed in all arterial vessel segments a non-statistically significant prolongation of rTmax after treatment. The mean CirT was 5.62 s (±1.19 s) pre-interventionally and 5.16 s (±0.81 s) post-interventionally, and the difference turned out as statistically significant (p = 0.039). A significantly increased diameter was measurable in all arterial segments post-interventionally.PCC is a fast applicable imaging technique that allows via real-time and in vivo blood flow analysis a quantitative assessment of the effect of intra-arterial vasospasm therapy. Our results seem to validate in vivo that an intra-arterial nimodipine application induces not only vasodilatation of the larger vessels, but also improves the microcirculatory flow, leading to a shortened cerebral CirT that reaches normal range post-interventionally. Procedural monitoring via PCC offers the option to compare quantitatively different therapy regimes, which allows optimization of existing approaches and implementation of individualized treatment strategies.
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Real world application of ocrelizumab in multiple sclerosis: Single-center experience of 128 patients - Prockl, Victoria; Nickel, Franziska; Utz, Kathrin S.; Fröhlich, Kilian; Engelhorn, Tobias; Hilz, Max-Josef; Lee, De-Hyung; Linker, Ralf; Huhn, Konstantin (Journal of the Neurological Sciences, 2020)
Background: Pivotal trials showed good clinical efficiency of the monoclonal antibody ocrelizumab while being well tolerated and manageable in multiple sclerosis (MS). However, data on adverse events in everyday practice are scarce. Hence, our study aims at investigating short-term tolerability of ocrelizumab in a “real-world” setting. Methods: In this retrospective cohort study, data of 128 (86 relapsing-remitting, 42 progressive) MS patients at initiation of ocrelizumab were analyzed at the MS center of the University of Erlangen, Germany. Additionally, follow-up data of 68 patients at 6-months retreatment were analyzed. Structured phone interviews were applied after ocrelizumab initiation to report undocumented side effects. Results: Patients predominantly switched from monoclonal antibodies (46%), orals (20%), injectables (10%), steroids or immunosuppressants (each 8%), with a mean interval of 9.0 months after the last application of the previous immunotherapy. Applying a combined premedication with steroids, antihistamines and antipyretics for >90% of patients, ocrelizumab treatment was well tolerated and mainly comprised mild (n = 59/128 at initiation, n = 5/68 at 6 months retreatment) and rarely moderate (n = 7/128 at initiation, n = 2/68 at 6 months) side effects. Predominantly mild infusion related reactions (IRR) were reported with a declining percentage over the follow-up applications. Infections occurred rarely. No severe side effects were observed. Secondary, treatment appeared efficient when looking at clinical surrogates of stable disease. Discussion: Our study delineates good short-term tolerability of ocrelizumab in a miscellaneous “real-world” MS cohort. Additional studies are warranted to confirm these beneficial findings and to reveal safety concerns in the longer-term follow-up.
CRIS-Team Scopus Importer:2020-06-26
Keywords: B-cell depletion; CD 20; Immunomodulatory treatment; Monoclonal antibody; Multiple sclerosis; Ocrelizumab; Side effects

Real-World Stair Ambulation Characteristics Differ Between Prospective Fallers and Non-Fallers in Parkinson’s Disease - Roth, Nils; Ullrich, Martin; Küderle, Arne; Gladow, Till; Marxreiter, Franz; Gaßner, Heiko; Kluge, Felix; Klucken, Jochen; Eskofier, Björn (IEEE Journal of Biomedical and Health Informatics, 2022)
Falls are among the leading causes of injuries or death for individuals from the age of 65 and the prevalence of falls is especially high for patients suffering from neurological diseases like Parkinson’s disease (PD). Due to advancements in wearable sensor technology, inertial measurement units (IMUs) can be integrated unobtrusively into patients’ everyday lives to monitor various mobility and gait parameters, which are related to common risk factors like reduced balance and reduced lower-limb muscle strength, or lower range of joints. Although stair ambulation is a fundamental part of our daily lives and is known for its unique challenges for the gait and balance system, long-term gait analysis studies have not investigated real-world stair ambulation parameters yet. Therefore, we applied a recently published gait analysis pipeline on real-world foot-worn IMU data of 40 PD patients over a recording period of two weeks to extract objective gait parameters from level walking but also from stair ascending and stair descending gait. In combination with fall records from a prospective three-month follow-up phase, we investigated group differences in gait parameters of future fallers compared to non-fallers for each individual gait activity. We found significant differences in stair ascending and descending parameters. Stance time was increased by up to 20% and gait speed reduced by up to 16% for fallers compared to non-fallers during stair walking. These differences were not present in level walking parameters. Hence, these results suggest that real-world stair ambulation provides sensitive parameters for mobility and fall risk due to the unique challenges stairs add to the balance and control system. Our work complements existing gait analysis studies by adding new insights into mobility and gait performance during real-world gait.
CRIS-Team Scopus Importer:2022-07-22
Keywords: ascending; Biomedical monitoring; descending; fall risk; free-living; gait analysis; Hospitals; inertial measurement unit; Legged locomotion; Monitoring; Stairs; Three-dimensional displays; Wearable sensors

Recent Machine Learning Advancements in Sensor-Based Mobility Analysis: Deep Learning for Parkinson’s Disease Assessment - Eskofier, Björn; Lee, Sunghoon I.; Daneault, Jean-Francois; Golabchi, Fatemeh N.; Ferreira-Carvalho, Gabriela; Vergara-Diaz, Gloria; Sapienza, Stefano; Costante, Gianluca; Klucken, Jochen; Kautz, Thomas; Bonato, Paolo (Proceedings of the 38th IEEE Engineering in Medicine and Biology Society Conference (EMBC 2016), 2016)
The development of wearable sensors has opened the door for long-term assessment of movement disorders. However, there is still a need for developing methods suitable to monitor motor symptoms in and outside the clinic. The purpose of this paper was to investigate deep learning as a method for this monitoring. Deep learning recently broke records in speech and image classification, but it has not been fully investigated as a potential approach to analyze wearable sensor data. We collected data from ten patients with idiopathic Parkinson’s disease using inertial measurement units. Several motor tasks were expert-labeled and used for classification. We specifically focused on the detection of bradykinesia. For this, we compared standard machine learning pipelines with deep learning based on convolutional neural networks. Our results showed that deep learning outperformed other state-of-the-art machine learning algorithms by at least 4.6 % in terms of classification rate. We contribute a discussion of the advantages and disadvantages of deep learning for sensor-based movement assessment and conclude that deep learning is a promising method for this field.

Recombinant pro-CTSD (cathepsin D) enhances SNCA/α-Synuclein degradation in α-Synucleinopathy models. - Huarcaya, Alice Prieto; Drobny, Susy; Marques, Andre R. A.; Di Spiezio, Alessandro; Dobert, Jan; Balta, Denise; Werner, Christian; Rizo Garza, Tania; Gallwitz, Lisa; Bub, Simon; Stojkovska, Iva; Belur, Nandkishore R.; et al. (Autophagy, 2022)
Parkinson disease (PD) is a neurodegenerative disorder characterized by the abnormal intracellular accumulation of SNCA/α-synuclein. While the exact mechanisms underlying SNCA pathology are not fully understood, increasing evidence suggests the involvement of autophagy as well as lysosomal deficiencies. Because CTSD (cathepsin D) has been proposed to be the major lysosomal protease involved in SNCA degradation, its deficiency has been linked to the presence of insoluble SNCA conformers in the brain of mice and humans as well as to the transcellular transmission of SNCA aggregates. We here postulate that SNCA degradation can be enhanced by the application of the recombinant human proform of CTSD (rHsCTSD). Our results reveal that rHsCTSD is efficiently endocytosed by neuronal cells, correctly targeted to lysosomes and matured to an enzymatically active protease. In dopaminergic neurons derived from induced pluripotent stem cells (iPSC) of PD patients harboring the A53T mutation within the SNCA gene, we confirm the reduction of insoluble SNCA after treatment with rHsCTSD. Moreover, we demonstrate a decrease of pathological SNCA conformers in the brain and within primary neurons of a ctsd-deficient mouse model after dosing with rHsCTSD. Boosting lysosomal CTSD activity not only enhanced SNCA clearance in human and murine neurons as well as tissue, but also restored endo-lysosome and autophagy function. Our findings indicate that CTSD is critical for SNCA clearance and function. Thus, enzyme replacement strategies utilizing CTSD may also be of therapeutic interest for the treatment of PD and other synucleinopathies aiming to decrease the SNCA burden.Abbreviations: aa: amino acid; SNCA/α-synuclein: synuclein alpha; APP: amyloid beta precursor protein; BBB: blood brain barrier; BF: basal forebrain; CBB: Coomassie Brilliant Blue; CLN: neuronal ceroid lipofuscinosis; CNL10: neuronal ceroid lipofuscinosis type 10; Corr.: corrected; CTSD: cathepsin D; CTSB: cathepsin B; DA: dopaminergic; DA-iPSn: induced pluripotent stem cell-derived dopaminergic neurons; dox: doxycycline; ERT: enzyme replacement therapy; Fx: fornix, GBA/β-glucocerebrosidase: glucosylceramidase beta; h: hour; HC: hippocampus; HT: hypothalamus; i.c.: intracranially; IF: immunofluorescence; iPSC: induced pluripotent stem cell; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LSDs: lysosomal storage disorders; MAPT: microtubule associated protein tau; M6P: mannose-6-phosphate; M6PR: mannose-6-phosphate receptor; MB: midbrain; mCTSD: mature form of CTSD; neurofil.: neurofilament; PD: Parkinson disease; proCTSD: proform of CTSD; PRNP: prion protein; RFU: relative fluorescence units; rHsCTSD: recombinant human proCTSD; SAPC: Saposin C; SIM: structured illumination microscopy; T-insol: Triton-insoluble; T-sol: Triton-soluble; TEM: transmission electron microscopy, TH: tyrosine hydroxylase; Thal: thalamus.
Keywords: alpha-synuclein; cathepsin D; lysosomal degradation; lysosomal storage disorders; parkinson disease; synucleinopathies

Recommendations for Standards of Network Care for Patients with Parkinson's Disease in Germany - Prell, Tino; Siebecker, Frank; Lorrain, Michael; Eggers, Carsten; Lorenzl, Stefan; Klucken, Jochen; Warnecke, Tobias; Buhmann, Carsten; Tonges, Lars; Ehret, Reinhard; Wellach, Ingmar; Wolz, Martin (Journal of Clinical Medicine, 2020)
Although our understanding of Parkinson's disease (PD) has improved and effective treatments are available, caring for people with PD remains a challenge. The large heterogeneity in terms of motor symptoms, nonmotor symptoms, and disease progression makes tailored individual therapy and individual timing of treatment necessary. On the other hand, only limited resources are available for a growing number of patients, and the high quality of treatment cannot be guaranteed across the board. At this point, networks can help to make better use of resources and improve care. The working group PD Networks and Integrated Care, part of the German Parkinson Society, is entrusted to convene clinicians, therapists, nurses, researchers, and patients to promote the development of PD networks. This article summarizes the work carried out by the working group PD Networks and Integrated Care in the development of standards of network care for patients with PD in Germany.
CRIS-Team WoS Importer:2020-06-26

Recommendations for the management of cerebral and cerebellar infarction with swelling: a statement for healthcare professionals from the American Heart Association/American Stroke Association - Wijdicks, Eelco F. M.; Sheth, Kevin N.; Carter, Bob S.; Greer, David M.; Kasner, Scott E.; Kimberly, W. Taylor; Schwab, Stefan; Smith, Eric E.; Tamargo, Rafael J.; Wintermark, Max (Stroke, 2014)
There are uncertainties surrounding the optimal management of patients with brain swelling after an ischemic stroke. Guidelines are needed on how to manage this major complication, how to provide the best comprehensive neurological and medical care, and how to best inform families facing complex decisions on surgical intervention in deteriorating patients. This scientific statement addresses the early approach to the patient with a swollen ischemic stroke in a cerebral or cerebellar hemisphere.The writing group used systematic literature reviews, references to published clinical and epidemiology studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize existing evidence and to indicate gaps in current knowledge. The panel reviewed the most relevant articles on adults through computerized searches of the medical literature using MEDLINE, EMBASE, and Web of Science through March 2013. The evidence is organized within the context of the American Heart Association framework and is classified according to the joint American Heart Association/American College of Cardiology Foundation and supplementary American Heart Association Stroke Council methods of classifying the level of certainty and the class and level of evidence. The document underwent extensive American Heart Association internal peer review.Clinical criteria are available for hemispheric (involving the entire middle cerebral artery territory or more) and cerebellar (involving the posterior inferior cerebellar artery or superior cerebellar artery) swelling caused by ischemic infarction. Clinical signs that signify deterioration in swollen supratentorial hemispheric ischemic stroke include new or further impairment of consciousness, cerebral ptosis, and changes in pupillary size. In swollen cerebellar infarction, a decrease in level of consciousness occurs as a result of brainstem compression and therefore may include early loss of corneal reflexes and the development of miosis. Standardized definitions should be established to facilitate multicenter and population-based studies of incidence, prevalence, risk factors, and outcomes. Identification of patients at high risk for brain swelling should include clinical and neuroimaging data. If a full resuscitative status is warranted in a patient with a large territorial stroke, admission to a unit with neurological monitoring capabilities is needed. These patients are best admitted to intensive care or stroke units attended by skilled and experienced physicians such as neurointensivists or vascular neurologists. Complex medical care includes airway management and mechanical ventilation, blood pressure control, fluid management, and glucose and temperature control. In swollen supratentorial hemispheric ischemic stroke, routine intracranial pressure monitoring or cerebrospinal fluid diversion is not indicated, but decompressive craniectomy with dural expansion should be considered in patients who continue to deteriorate neurologically. There is uncertainty about the efficacy of decompressive craniectomy in patients >=60 years of age. In swollen cerebellar stroke, suboccipital craniectomy with dural expansion should be performed in patients who deteriorate neurologically. Ventriculostomy to relieve obstructive hydrocephalus after a cerebellar infarct should be accompanied by decompressive suboccipital craniectomy to avoid deterioration from upward cerebellar displacement. In swollen hemispheric supratentorial infarcts, outcome can be satisfactory, but one should anticipate that one third of patients will be severely disabled and fully dependent on care even after decompressive craniectomy. Surgery after a cerebellar infarct leads to acceptable functional outcome in most patients.Swollen cerebral and cerebellar infarcts are critical conditions that warrant immediate, specialized neurointensive care and often neurosurgical intervention. Decompressive craniectomy is a necessary option in many patients. Selected patients may benefit greatly from such an approach, and although disabled, they may be functionally independent.
EVALuna2:22286

Recommendations for the Organization of Multidisciplinary Clinical Care Teams in Parkinson's Disease - Radder, Danique L. M.; Nonnekes, Jorik; Nimwegen, Marlies Van; Eggers, Carsten; Abbruzzese, Giovanni; Alves, Guido; Browner, Nina; Chaudhuri, K. Ray; Ebersbach, Georg; Ferreira, Joaquim J.; Fleisher, Jori E.; Fletcher, Peter; et al. (Journal of Parkinson's Disease, 2020)
BACKGROUND: Optimal management in expert centers for Parkinson's disease (PD) usually involves pharmacological and non-pharmacological interventions, delivered by a multidisciplinary approach. However, there is no guideline specifying how this model should be organized. Consequently, the nature of multidisciplinary care varies widely. OBJECTIVE: To optimize care delivery, we aimed to provide recommendations for the organization of multidisciplinary care in PD. METHODS: Twenty expert centers in the field of multidisciplinary PD care participated. Their leading neurologists completed a survey covering eight themes: elements for optimal multidisciplinary care; team members; role of patients and care partners; team coordination; team meetings; inpatient versus outpatient care; telehealth; and challenges towards multidisciplinary care. During a consensus meeting, outcomes were incorporated into concept recommendations that were reviewed by each center's multidisciplinary team. Three patient organizations rated the recommendations according to patient priorities. Based on this feedback, a final set of recommendations (essential elements for delivery of multidisciplinary care) and considerations (desirable elements) was developed. RESULTS: We developed 30 recommendations and 10 considerations. The patient organizations rated the following recommendations as most important: care is organized in a patient-centered way; every newly diagnosed patient has access to a core multidisciplinary team; and each team has a coordinator. A checklist was created to further facilitate its implementation. CONCLUSION: We provide a practical tool to improve multidisciplinary care for persons with PD at the organizational level. Future studies should focus on implementing these recommendations in clinical practice, evaluating their potential applicability and effectiveness, and comparing alternative models of PD care.
CRIS-Team Scopus Importer:2020-08-14
Keywords: guideline; interdisciplinary; multidisciplinary; organization of care; Parkinson’s disease; practice-based evidence

Recommendations for tilt table testing and other provocative cardiovascular autonomic tests in conditions that may cause transient loss of consciousness : Consensus statement of the European Federation of Autonomic Societies (EFAS) endorsed by the American Autonomic Society (AAS) and the European Academy of Neurology (EAN). - Thijs, Roland D.; Brignole, Michele; Falup-Pecurariu, Cristian; Fanciulli, Alessandra; Freeman, Roy; Guaraldi, Pietro; Jordan, Jens; Habek, Mario; Hilz, Max-Josef; Pavy-Letraon, Anne; Stankovic, Iva; Struhal, Walter; et al. (Autonomic Neuroscience-Basic & Clinical, 2021)
An expert committee was formed to reach consensus on the use of Tilt Table Testing (TTT) in the diagnosis of disorders that may cause transient loss of consciousness (TLOC) and to outline when other provocative cardiovascular autonomic tests are needed. While TTT adds to history taking, it cannot be a substitute for it. An abnormal TTT result is most meaningful if the provoked event is recognised by patients or eyewitnesses as similar to spontaneous ones. The minimum requirements to perform TTT are a tilt table, a continuous beat-to-beat blood pressure monitor, at least one ECG lead, protocols for the indications stated below and trained staff. This basic equipment lends itself to perform (1) additional provocation tests, such as the active standing test carotid sinus massage and autonomic function tests; (2) additional measurements, such as video, EEG, transcranial Doppler, NIRS, end-tidal CO2 or neuro-endocrine tests; (3) tailor-made provocation procedures in those with a specific and consistent trigger of TLOC. TTT and other provocative cardiovascular autonomic tests are indicated if the initial evaluation does not yield a definite or highly likely diagnosis, but raises a suspicion of (1) reflex syncope, (2) the three forms of orthostatic hypotension (OH), i.e. initial, classic and delayed OH, as well as delayed orthostatic blood pressure recovery, (3) postural orthostatic tachycardia syndrome or (4) psychogenic pseudosyncope. A therapeutic indication for TTT is to teach patients with reflex syncope and OH to recognise hypotensive symptoms and to perform physical counter manoeuvres.
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Recommendations for tilt table testing and other provocative cardiovascular autonomic tests in conditions that may cause transient loss of consciousness Consensus statement of the European Federation of Autonomic Societies (EFAS) endorsed by the American Autonomic Society (AAS) and the European Academy of Neurology (EAN) - Thijs, Roland D.; Brignole, Michele; Falup-Pecurariu, Cristian; Fanciulli, Alessandra; Freeman, Roy; Guaraldi, Pietro; Jordan, Jens; Habek, Mario; Hilz, Max-Josef; Traon, Anne Pavy-Le; Stankovic, Iva; Struhal, Walter; et al. (Clinical Autonomic Research, 2021)
An expert committee was formed to reach consensus on the use of tilt table testing (TTT) in the diagnosis of disorders that may cause transient loss of consciousness (TLOC) and to outline when other provocative cardiovascular autonomic tests are needed. While TTT adds to history taking, it cannot be a substitute for it. An abnormal TTT result is most meaningful if the provoked event is recognised by patients or eyewitnesses as similar to spontaneous events. The minimum requirements to perform TTT are a tilt table, a continuous beat-to-beat blood pressure monitor, at least one ECG lead, protocols for the indications stated below and trained staff. This basic equipment lends itself to the performance of (1) additional provocation tests, such as the active standing test, carotid sinus massage and autonomic function tests; (2) additional measurements, such as video, EEG, transcranial Doppler, NIRS, end-tidal CO2 or neuro-endocrine tests; and (3) tailor-made provocation procedures in those with a specific and consistent trigger of TLOC. TTT and other provocative cardiovascular autonomic tests are indicated if the initial evaluation does not yield a definite or highly likely diagnosis, but raises a suspicion of (1) reflex syncope, (2) the three forms of orthostatic hypotension (OH), i.e. initial, classic and delayed OH, as well as delayed orthostatic blood pressure recovery, (3) postural orthostatic tachycardia syndrome or (4) psychogenic pseudosyncope. A therapeutic indication for TTT is to teach patients with reflex syncope and OH to recognise hypotensive symptoms and to perform physical counter manoeuvres.
CRIS-Team WoS Importer:2021-04-02

Recommendations on the structure, personal, and organization of intensive care units - Waydhas, Christian; Riessen, Reimer; Markewitz, Andreas; Hoffmann, Florian; Frey, Lorenz; Böttiger, Bernd W.; Brenner, Sebastian; Brenner, Thorsten; Deffner, Teresa; Deininger, Matthias M.; Janssens, Uwe; Kluge, Stefan; et al. (Frontiers in Medicine, 2023)
Background: Intensive care units (ICU) are central facilities of medical care in hospitals world-wide and pose a significant financial burden on the health care system. Objectives: To provide guidance and recommendations for the requirements of (infra)structure, personal, and organization of intensive care units. Design and setting: Development of recommendations based on a systematic literature search and a formal consensus process from a group of multidisciplinary and multiprofessional specialists from the German Interdisciplinary Association of Intensive Care and Emergency Medicine (DIVI). The grading of the recommendation follows the report from an American College of Chest Physicians Task Force. Results: The recommendations cover the fields of a 3-staged level of intensive care units, a 3-staged level of care with respect to severity of illness, qualitative and quantitative requirements of physicians and nurses as well as staffing with physiotherapists, pharmacists, psychologists, palliative medicine and other specialists, all adapted to the 3 levels of ICUs. Furthermore, proposals concerning the equipment and the construction of ICUs are supplied. Conclusion: This document provides a detailed framework for organizing and planning the operation and construction/renovation of ICUs.
CRIS-Team Scopus Importer:2023-09-29
Keywords: guideline; intensive care medicine; organization; personal; quality of care; recommendation; structural requirements

Reduced Cancer Incidence in Huntington's Disease: Analysis in the Registry Study - Mcnulty, Paul; Pilcher, Richard; Ramesh, Raviram; Necuiniate, Renata; Hughes, Alis; Winkler, Jürgen; Farewell, Daniel; Holmans, Peter; Jones, Lesley (Journal of Huntington's Disease, 2018)
Background: People with Huntington's disease (HD) have been observed to have lower rates of cancers. Objective: To investigate the relationship between age of onset of HD, CAG repeat length, and cancer diagnosis. Methods: Data were obtained from the European Huntington's disease network REGISTRY study for 6540 subjects. Population cancer incidence was ascertained from the GLOBOCAN database to obtain standardised incidence ratios of cancers in the REGISTRY subjects. Results: 173/6528 HD REGISTRY subjects had had a cancer diagnosis. The age-standardised incidence rate of all cancers in the REGISTRY HD population was 0.26 (CI 0.22-0.30). Individual cancers showed a lower age-standardised incidence rate compared with the control population with prostate and colorectal cancers showing the lowest rates. There was no effect of CAG length on the likelihood of cancer, but a cancer diagnosis within the last year was associated with a greatly increased rate of HD onset (Hazard Ratio 18.94, p < 0.001). Conclusions: Cancer is less common than expected in the HD population, confirming previous reports. However, this does not appear to be related to CAG length in HTT. A recent diagnosis of cancer increases the risk of HD onset at any age, likely due to increased investigation following a cancer diagnosis.
CRIS-Team Scopus Importer:2021-07-19
Keywords: cancer; Huntington's disease; neurodegeneration; trinucleotide repeat

Reduced pupillary modulation in patients with relapsing-remitting Multiple Sclerosis is associated with longer disease duration and higher disease severity - Wang, Ruihao; Roy, Sankanika; de Rojas Leal, Carmen; Liu, Mao; Hoesl, K.; Lee, De-Hyung; Linker, Ralf; Hilz, Max-Josef (2018)
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Reduced synaptic activity and dysregulated extracellular matrix pathways in midbrain neurons from Parkinson’s disease patients - Stern, Shani; Lau, Shong; Manole, Andreea; Rosh, Idan; Percia, Menachem Mendel; Ben Ezer, Ran; Shokhirev, Maxim N.; Qiu, Fan; Schafer, Simon; Mansour, Abed Alfatah; Mangan, Kile P.; Stern, Tchelet; et al. (npj Parkinson’s Disease, 2022)
Several mutations that cause Parkinson’s disease (PD) have been identified over the past decade. These account for 15–25% of PD cases; the rest of the cases are considered sporadic. Currently, it is accepted that PD is not a single monolithic disease but rather a constellation of diseases with some common phenotypes. While rodent models exist for some of the PD-causing mutations, research on the sporadic forms of PD is lagging due to a lack of cellular models. In our study, we differentiated PD patient-derived dopaminergic (DA) neurons from the induced pluripotent stem cells (iPSCs) of several PD-causing mutations as well as from sporadic PD patients. Strikingly, we observed a common neurophysiological phenotype: neurons derived from PD patients had a severe reduction in the rate of synaptic currents compared to those derived from healthy controls. While the relationship between mutations in genes such as the SNCA and LRRK2 and a reduction in synaptic transmission has been investigated before, here we show evidence that the pathogenesis of the synapses in neurons is a general phenotype in PD. Analysis of RNA sequencing results displayed changes in gene expression in different synaptic mechanisms as well as other affected pathways such as extracellular matrix-related pathways. Some of these dysregulated pathways are common to all PD patients (monogenic or idiopathic). Our data, therefore, show changes that are central and convergent to PD and suggest a strong involvement of the tetra-partite synapse in PD pathophysiology.
CRIS-Team Scopus Importer:2022-08-26

Reduction in subventricular zone-derived olfactory bulb neurogenesis in a rat model of Huntington's disease is accompanied by striatal invasion of neuroblasts - Kandasamy, Mahesh; Rosskopf, Michael; Wagner, Katrin; Klein, Barbara; Couillard-Despres, Sebastien; Reitsamer, Herbert A.; Stephan, Michael; Nguyen, Huu Phuc; Riess, Olaf; Bogdahn, Ulrich; Winkler, Jürgen; von Hörsten, Stephan; et al. (PLoS ONE, 2015)
Huntington's disease (HD) is an inherited progressive neurodegenerative disorder caused by an expanded CAG repeat in exon 1 of the huntingtin gene (HTT). The primary neuropathology of HD has been attributed to the preferential degeneration of medium spiny neurons (MSN) in the striatum. Reports on striatal neurogenesis have been a subject of debate; nevertheless, it should be considered as an endogenous attempt to repair the brain. The subventricular zone (SVZ) might offer a close-by region to supply the degenerated striatum with new cells. Previously, we have demonstrated that R6/2 mice, a widely used preclinical model representing an early onset HD, showed reduced olfactory bulb (OB) neurogenesis but induced striatal migration of neuroblasts without affecting the proliferation of neural progenitor cell (NPCs) in the SVZ. The present study revisits these findings, using a clinically more relevant transgenic rat model of late onset HD (tgHD rats) carrying the human HTT gene with 51 CAG repeats and mimicking many of the neuropathological features of HD seen in patients. We demonstrate that cell proliferation is reduced in the SVZ and OB of tgHD rats compared to WT rats. In the OB of tgHD rats, although cell survival was reduced, the frequency of neuronal differentiation was not altered in the granule cell layer (GCL) compared to the WT rats. However, an increased frequency of dopamenergic neuronal differentiation was noticed in the glomerular layer (GLOM) of tgHD rats. Besides this, we observed a selective proliferation of neuroblasts in the adjacent striatum of tgHD rats. There was no evidence for neuronal maturation and survival of these striatal neuroblasts. Therefore, the functional role of these invading neuroblasts still needs to be determined, but they might offer an endogenous alternative for stem or neuronal cell transplantation strategies.
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Re-evaluation of the stroke prognostication using age and NIH Stroke Scale index (SPAN-100 index) in IVT patients - the-SPAN 10065 index - Möbius, Cornelia; Blinzler, Christian; Schwab, Stefan; Koehrmann, Martin; Breuer, Lorenz (BMC Neurology, 2018)
BACKGROUND: The SPAN-100 index adds patient age and baseline NIHSS-score and was introduced to predict clinical outcome after acute ischemic stroke (AIS). Even with high NIHSS-scores younger patients cannot reach a SPAN-100-positive status (index ≥100). We aimed to evaluate the SPAN-100 index among a large, contemporary cohort of i.v.-thrombolysed AIS-patients and exclusively among older patients who can at least theoretically achieve SPAN-100-positivity. METHODS: The SPAN-100 index was applied to AIS-patients receiving i.v.-thrombolysis (IVT) in our institution between 01/2006 and 01/2013. Clinical outcome and symptomatic intracerebral hemorrhage rates were compared between SPAN-100-positive and -negative patients. Furthermore we excluded patients < 65 years, without any theoretical chance to achieve SPAN-100-positivity, and re-evaluated the index (SPAN65-100 index). RESULTS: SPAN-100-positive IVT-patients (124/1002) had a 9-fold increased risk for unfavorable outcome compared to SPAN-negative patients (OR 9.39; 95% CI 5.87-15.02; p < 0.001). The odds ratio for mortality was 7.48 (95% CI 4.90-11.43; p < 0.001). No association was found between SPAN-100-positivity and sICH-incidence (OR 0.88; 95% CI 0.31-2.53; p = 0.810). SPAN65-100-positivity (124/741) was associated with an 8-fold increased risk for unfavorable outcome (OR 7.6; 95% CI 4.71-12.22; p < 0.001) but not associated with higher sICH-rates (OR 0.86; 95% CI 0.29-2.53; p < 0.001). CONCLUSIONS: Also for patients ≥65 years the SPAN-100 index can be a fast, easy method to predict clinical outcome of IVT-patients in everyday practice. However, it should not be used to determine the risk of sICH after IVT. Based on a SPAN-positive status IVT should not be withheld from AIS-patients merely because of feared sICH-complications.
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Regional Differences in Thrombectomy Rates : Secondary use of Billing Codes in the MIRACUM (Medical Informatics for Research and Care in University Medicine) Consortium - Haverkamp, Christian; Ganslandt, Thomas; Horki, Petar; Boeker, Martin; Dörfler, Arnd; Schwab, Stefan; Berkefeld, Joachim; Pfeilschifter, Waltraud; Niesen, Wolf-Dirk; Egger, Karl; Kaps, Manfred; Brockmann, Marc A.; et al. (Clinical Neuroradiology, 2018)
Mechanical thrombectomy, in addition to intravenous (i.v.) thrombolysis is recommended for treatment of acute stroke in patients with large vessel occlusions (LVO) in the anterior circulation up to 6 h after symptom onset. We compared thrombectomy rates of eight university hospitals of the MIRACUM consortium to analyze the implementation of this guideline in clinical routine.Anonymized billing data in a standardized format were loaded into a local i2b2 data warehouse by applying already existing extract, transform and load (ETL) routines. A locally executed uniform SQL (structured query language) query delivered aggregated site data for all inpatients with a discharge diagnosis of ischemic stroke (ICD-10 I63) containing counts for type of acute treatment, type of admission and age groups, which were centrally analyzed with R.From 2014 to 2016, the thrombectomy rate almost doubled from a mean of 4.7% to 9.6%, although significant differences between centers exist (range in 2016: 5.8-17%). The number of drip-and-ship procedures increased in 3 out of 8 centers. There was no evidence for a decrease in thrombectomy rates during weekends/holiday or among patients older than 80 years, but this age group is more likely to receive i.v. recombinant tissue plasminogen activator (rtPA).The observed increase of thrombectomy rates and drip-and-ship procedures without a significant difference between weekdays and weekends or patients of different ages is substantiating a rapid implementation of stroke guidelines within the analyzed neurovascular centers. The prototype of the MIRACUM Data Integration Center already contributes to health services research in Germany.
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Regulation of the programmed cell death protein 1/programmed cell death ligand 1 axis in relapsing-remitting multiple sclerosis - Tsaktanis, Thanos; Linnerbauer, Mathias; Lößlein, Lena; Farrenkopf, Daniel; Vandrey, Oliver; Peter, Anne; Cirac, Ana; Beyer, Tobias; Nirschl, Lucy; Grummel, Verena; Mühlau, Mark; Bussas, Matthias; et al. (Brain Communications, 2023)
The programmed cell death protein 1/programmed cell death ligand 1 axis plays an important role in the adaptive immune system and has influence on neoplastic and inflammatory diseases, while its role in multiple sclerosis is unclear. Here, we aimed to analyse expression patterns of programmed cell death protein 1 and programmed cell death ligand 1 on peripheral blood mononuclear cells and their soluble variants in multiple sclerosis patients and controls, to determine their correlation with clinical disability and disease activity. In a cross-sectional study, we performed in-depth flow cytometric immunophenotyping of peripheral blood mononuclear cells and analysed soluble programmed cell death protein 1 and programmed cell death ligand 1 serum levels in patients with relapsing-remitting multiple sclerosis and controls. In comparison to control subjects, relapsing-remitting multiple sclerosis patients displayed distinct cellular programmed cell death protein 1/programmed cell death ligand 1 expression patterns in immune cell subsets and increased soluble programmed cell death ligand 1 levels, which correlated with clinical measures of disability and MRI activity over time. This study extends our knowledge of how programmed cell death protein 1 and programmed cell death ligand 1 are expressed in the membranes of patients with relapsing-remitting multiple sclerosis and describes for the first time the elevation of soluble programmed cell death ligand 1 in the blood of multiple sclerosis patients. The distinct expression pattern of membrane-bound programmed cell death protein 1 and programmed cell death ligand 1 and the correlation between soluble programmed cell death ligand 1, membrane-bound programmed cell death ligand 1, disease and clinical factors may offer therapeutic potential in the setting of multiple sclerosis and might improve future diagnosis and clinical decision-making.
CRIS-Team Scopus Importer:2023-09-15
Keywords: autoimmunity; checkpoint; co-regulation; neuroinflammation; PBMCs

Relationship between Physical Activity and Mental Health in Multiple Sclerosis Patients without Limitation of Physical Function: A Cross-Sectional Explorative Study. - Tallner, Alexander; Pfeifer, Klaus; Wenny, Ingrid; Mäurer, Mathias; Waschbisch, Anne (Annual Meeting of the American Academy of Neurology, 2009)

Relevance of sonography for botulinum toxin treatment of cervical dystonia: an expert statement - Schramm, Axel; Baeumer, Tobias; Fietzek, Urban; Heitmann, Susanne; Walter, Uwe; Jost, Wolfgang H. (Journal of Neural Transmission, 2015)
Botulinum neurotoxin A (BoNT A) is the first-line treatment for cervical dystonia. However, although BoNT A has a favorable safety profile and is effective in the majority of patients, in some cases the treatment outcome is disappointing or side effects occur when higher doses are used. It is likely that in such cases either the target muscles were not injected accurately or unintended weakness of non-target muscles occurred. It has been demonstrated in clinical trials for spastic movement disorders that sonography-guided BoNT A injections could improve treatment outcome. As the published evidence for a benefit of sonography-guided BoNT injection in patients with cervical dystonia is scarce, it is the aim of this review to discuss the relevance of sonography in this indication and provide a statement from clinical experts for its use. The clear advantage of sonography-guided injections is non-invasive, real-time visualization of the targeted muscle, thus improving the precision of injections and potentially the treatment outcomes as well as avoiding adverse effects. Other imaging techniques are of limited value due to high costs, radiation exposure or non-availability in clinical routine. In the hands of a trained injector, sonography is a quick and non-invasive imaging technique. Novel treatment concepts of cervical dystonia considering the differential contributions of distinct cranial and cervical muscles can reliably be implemented only by use of imaging-guided injection protocols.
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Reliability and limitations of automated arrhythmia detection in telemetric monitoring after stroke - Kurka, Natalia; Bobinger, Tobias; Kallmünzer, Bernd; Koehn, Julia; Schellinger, Peter D.; Schwab, Stefan; Köhrmann, Martin (Stroke, 2015)
Guidelines recommend continuous ECG monitoring in patients with cerebrovascular events. Studies on intensive care units (ICU) demonstrated high sensitivity but high rates of false alarms of monitoring systems resulting in desensitization of medical personnel potentially endangering patient safety. Data on patients with acute stroke are lacking.One-hundred fifty-one consecutive patients with acute cerebrovascular events were prospectively included. Automatically identified arrhythmia events were analyzed by manual ECG analysis. Muting of alarms was registered. Sensitivity was evaluated by beat-to-beat analysis of the entire recorded ECG data in a subset of patients. Ethics approval was obtained by University of Erlangen-Nuremberg.A total of 4809.5 hours of ECG registration and 22 509 alarms were analyzed. The automated detection algorithm missed no events but the overall rate of false alarms was 27.4%. Only 0.6% of all alarms indicated acute life-threatening events and 91.4% of these alarms were incorrect. Transient muting of acoustic alarms was observed in 20.5% patients.Continuous ECG monitoring using automated arrhythmia detection is highly sensitive in acute stroke. However, high rates of false alarms and alarms without direct therapeutic consequence cause desensitization of personnel. Therefore, acoustic alarms may be limited to life-threatening events but standardized manual evaluation of all alarms should complement automated systems to identify clinically relevant arrhythmias.
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Reliability and validity of a new, sensor-based system for gait analysis in patients with multiple sclerosis - Flachenecker, F.; Gaßner, Heiko; Lee, De-Hyung; Eskofier, Björn; Klucken, Jochen; Flachenecker, P.; Linker, Ralf (2017)
EVALuna2:22575

Reliability of clinical and instrumented balance assessments in patients with Parkinson’s Disease - Steib, Simon; Gaßner, Heiko; Eskofier, Björn; Winkler, Jürgen; Pfeifer, Klaus; Klucken, Jochen (ISPGR World Congress, 2015)

Reply: Adult-onset distal spinal muscular atrophy: A new phenotype associated with KIF5A mutations - Brenner, David; Rosenbohm, Angela; Yilmaz, Ruestem; Mueller, Kathrin; Grehl, Torsten; Petri, Susanne; Meyer, Thomas; Grosskreutz, Julian; Weydt, Patrick; Ruf, Wolfgang; Neuwirth, Christoph; Weber, Markus; et al. (Brain, 2019)
CRIS-Team Scopus Importer:2021-07-19

Reply: Beneficial effects of exogenous CDP-choline (citicoline) in EAE - Skripuletz, Thomas; Gudi, Viktoria; Baumgärtner, Wolfgang; Linker, Ralf A.; Stangel, Martin (Brain, 2015)
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Reply: Is there evidence of a subordinate role of the hippocampal CA1 field for declarative memory formation? - Coras, Roland; Pauli, Elisabeth; Blümcke, Ingmar (Brain, 2015)
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Reply to "Laterality of motor control as revealed in biceps electromyography: Why seizures always start in the major hemisphere" - Hagge, Mareike; Hamer, Hajo (Clinical Neurophysiology, 2016)
EVALuna2:22450

Report on the 5'th scientific meeting of the " Verein zur Förderung des Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in Motzen, Germany, Oct. 25th - Oct. 27th, 2013 - Linker, Ralf; Magnus, Tim; Korn, Thomas; Kleinschnitz, Christoph; Meuth, Sven G.; Alexaki, Ismini; Berer, Kerstin; Brunkhorst, Robert; Göb, Eva; Groh, Janos; Grozdanov, Veselin; Haase, Nadine; et al. (Experimental & Translational Stroke Medicine, 2013)
From october 25th - 27th 2013, the 5th NEUROWIND e.V. meeting was held in Motzen, Brandenburg, Germany. This year more than 60 doctoral students and postdocs from over 25 different groups working in German university hospitals or research institutes attended the meeting to discuss their latest findings in the fields of neuroimmunology, neurodegeneration and neurovascular research. All participants appreciated the stimulating environment in Motzen, Brandenburg, and people took the opportunity for scientific exchange, discussion about ongoing projects and already started further collaborations. Like in the previous years, the symposium was regarded as a very well organized platform to support research of young investigators in Germany.According to the major aim of NEUROWIND e.V. to support younger researchers in Germany the 3rd NEUROWIND YOUNG SCIENTIST AWARD for experimental neurology was awarded to Ruth Stassart working in the group of Klaus Armin Nave and Wolfgang Brück (MPI Göttingen and Department of Neuropathology, Göttingen Germany). The successful work was published in Nature Neuroscience entitled " A role for Swann cell-derived neuregulin-1 in remyelination" This outstanding paper deals with the function of Schwann cell neuregulin as an endogenous factor for myelin repair. The award is endowed with 20.000 Euro sponsored by Merck Serono GmbH, Darmstadt, Germany (unrestricted educational grant).This year's keynote lecture was given by Albert Ludolph, Head of the Department of Neurology at the University Clinic of Ulm. Dr. Ludolph highlighted the particular role of individual scientists for the development of research concepts in Alzheimeŕs disease (AD) and frontotemporal dementia (FTD). © 2013 Linker et al.; licensee BioMed Central Ltd.
CRIS-Team Scopus Importer:2020-09-22

Resection of cerebral gangliogliomas causing drug-resistant epilepsy: short- and long-term outcomes using intraoperative MRI and neuronavigation - Sommer, Bjoern; Wimmer, Cornelia; Coras, Roland; Blümcke, Ingmar; Lorber, Bogdan; Hamer, Hajo; Stefan, Hermann; Buchfelder, Michael; Roessler, Karl (Neurosurgical Focus, 2015)
OBJECT Cerebral gangliogliomas (GGs) are highly associated with intractable epilepsy. Incomplete resection due to proximity to eloquent brain regions or misinterpretation of the resection amount is a strong negative predictor for local tumor recurrence and persisting seizures. A potential method for dealing with this obstacle could be the application of intraoperative high-field MRI (iopMRI) combined with neuronavigation. METHODS Sixty-nine patients (31 female, 38 male; median age 28.5 ± 15.4 years) suffering from cerebral GGs were included in this retrospective study. Five patients received surgery twice in the observation period. In 48 of the 69 patients, 1.5-T iopMRI combined with neuronavigational guidance was used. Lesions close to eloquent brain areas were resected with the implementation of preoperative diffusion tensor imaging tractography and blood oxygenation level-dependent functional MRI (15 patients). RESULTS Overall, complete resection was accomplished in 60 of 69 surgical procedures (87%). Two patients underwent biopsy only, and in 7 patients, subtotal resection was accomplished because of proximity to critical brain areas. Excluding the 2 biopsies, complete resection using neuronavigation/iopMRI was documented in 33 of 46 cases (72%) by intraoperative imaging. Remnant tumor mass was identified intraoperatively in 13 of 46 patients (28%). After intraoperative second-look surgery, the authors improved the total resection rate by 9 patients (up to 91% [42 of 46]). Of 21 patients undergoing conventional surgery, 14 (67%) had complete resection without the use of iopMRI. Regarding epilepsy outcome, 42 of 60 patients with seizures (70%) became completely seizure free (Engel Class IA) after a median follow-up time of 55.5 ± 36.2 months. Neurological deficits were found temporarily in 1 (1.4%) patient and permanently in 4 (5.8%) patients. CONCLUSIONS Using iopMRI combined with neuronavigation in cerebral GG surgery, the authors raised the rate of complete resection in this series by 19%. Given the fact that total resection is a strong predictor of long-term seizure control, this technique may contribute to improved seizure outcome and reduced neurological morbidity.
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Resection of dominant fusiform gyrus is associated with decline of naming function when temporal lobe epilepsy manifests after the age of five: A voxel-based lesion-symptom mapping study - Reindl, Caroline; Allgäuer, Andrea; Kleiser, Benedict; Onugoren, Müjgan Dogan; Lang, Johannes; Welte, Tamara; Stritzelberger, Jenny; Winder, Klemens; Schwarz, Michael; Gollwitzer, Stephanie; Trollmann, Regina; Rösch, Julie; et al. (NeuroImage: Clinical, 2022)
Objective: To determine patients’ characteristics and regions in the temporal lobe where resections lead to a decline in picture naming. Methods: 311 patients with left hemispheric dominance for language were included who underwent epilepsy surgery at the Epilepsy Center of Erlangen and whose picture naming scores (Boston Naming Test, BNT) were available preoperatively and 6-months postoperatively. Surgical lesions were mapped to an averaged template based on preoperative and postoperative MRI using voxel-based lesion-symptom mapping (VBLSM). Postoperative brain shifts were corrected. The relationship between lesioned brain areas and the presence of a postoperative naming decline was examined voxel-wise while controlling for effects of overall lesion size at first in the total cohort and then restricted to temporal lobe resections. Results: In VBLSM in the total sample, a decline in BNT score was significantly related to left temporal surgery. When only considering patients with left temporal lobe resections (n = 121), 40 (33.1%) significantly worsened in BNT postoperatively. VBLSM including all patients with left temporal resections generated no significant results within the temporal lobe. However, naming decline of patients with epilepsy onset after 5 years of age was significantly associated with resections in the left inferior temporal (extent of BNT decline range: 10.8− 14.4%) and fusiform gyrus (decline range: 12.1−18.4%). Significance: Resections in the posterior part of the dominant fusiform and inferior temporal gyrus was associated with a risk of deterioration in naming performance at six months after surgery in patients with epilepsy onset after 5 years of age but not with earlier epilepsy onset.
CRIS-Team Scopus Importer:2022-08-19
Keywords: Basal temporal language area; Epilepsy surgery; Gyrus fusiformis; Lesion localization; Naming; Neuropsychological outcome

Resective surgery for medically refractory epilepsy using intraoperative MRI and functional neuronavigation: the Erlangen experience of 415 patients - Roessler, Karl; Hofmann, Andrea; Sommer, Bjoern; Grummich, Peter; Coras, Roland; Kasper, Burkhard; Hamer, Hajo; Blümcke, Ingmar; Stefan, Hermann; Nimsky, Christopher; Buchfelder, Michael (Neurosurgical Focus, 2016)
Intraoperative overestimation of resection volume in epilepsy surgery is a well-known problem that can lead to an unfavorable seizure outcome. Intraoperative MRI (iMRI) combined with neuronavigation may help surgeons avoid this pitfall and facilitate visualization and targeting of sometimes ill-defined heterogeneous lesions or epileptogenic zones and may increase the number of complete resections and improve seizure outcome.To investigate this hypothesis, the authors conducted a retrospective clinical study of consecutive surgical procedures performed during a 10-year period for epilepsy in which they used neuronavigation combined with iMRI and functional imaging (functional MRI for speech and motor areas; diffusion tensor imaging for pyramidal, speech, and visual tracts; and magnetoencephalography and electrocorticography for spike detection). Altogether, there were 415 patients (192 female and 223 male, mean age 37.2 years; 41% left-sided lesions and 84.9% temporal epileptogenic zones). The mean preoperative duration of epilepsy was 17.5 years. The most common epilepsy-associated pathologies included hippocampal sclerosis (n = 146 [35.2%]), long-term epilepsy-associated tumor (LEAT) (n = 67 [16.1%]), cavernoma (n = 45 [10.8%]), focal cortical dysplasia (n = 31 [7.5%]), and epilepsy caused by scar tissue (n = 23 [5.5%]).In 11.8% (n = 49) of the surgeries, an intraoperative second-look surgery (SLS) after incomplete resection verified by iMRI had to be performed. Of those incomplete resections, LEATs were involved most often (40.8% of intraoperative SLSs, 29.9% of patients with LEAT). In addition, 37.5% (6 of 16) of patients in the diffuse glioma group and 12.9% of the patients with focal cortical dysplasia underwent an SLS. Moreover, iMRI provided additional advantages during implantation of grid, strip, and depth electrodes and enabled intraoperative correction of electrode position in 13.0% (3 of 23) of the cases. Altogether, an excellent seizure outcome (Engel Class I) was found in 72.7% of the patients during a mean follow-up of 36 months (range 3 months to 10.8 years). The greatest likelihood of an Engel Class I outcome was found in patients with cavernoma (83.7%), hippocampal sclerosis (78.8%), and LEAT (75.8%). Operative revisions that resulted from infection occurred in 0.3% of the patients, from hematomas in 1.6%, and from hydrocephalus in 0.8%. Severe visual field defects were found in 5.2% of the patients, aphasia in 5.7%, and hemiparesis in 2.7%, and the total mortality rate was 0%.Neuronavigation combined with iMRI was beneficial during surgical procedures for epilepsy and led to favorable seizure outcome with few specific complications. A significantly higher resection volume associated with a higher chance of favorable seizure outcome was found, especially in lesional epilepsy involving LEAT or diffuse glioma.
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Response to Gurevich and colleagues: The effect of enzyme replacement therapy on clinical outcomes in male patients with Fabry disease: a systematic literature review by a European panel of experts - Germain, Dominique P.; Falissard, B.; Hilz, Max-Josef; Spada, M.; Wanner, Christoph; Elliott, Perry M. (Molecular Genetics and Metabolism Reports, 2019)
CRIS-Team Scopus Importer:2019-08-30
Keywords: Agalsidase alfa; Agalsidase beta; Enzyme replacement therapy; Fabry disease

Restarting Therapeutic Anticoagulation in Patients with Intracerebral Hemorrhage and Mechanical Heart Valves - Kuramatsu, Joji; Sembill, Jochen; Schwab, Stefan; Huttner, Hagen (2018)
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Resumption of oral anticoagulation after spontaneous intracerebral hemorrhage - Sembill, Jochen; Kuramatsu, Joji; Schwab, Stefan; Huttner, Hagen (Neurological Research and Practice, 2019)
Background: Given an ageing population the incidence of both patients suffering from intracerebral hemorrhage (ICH) and those requiring oral anticoagulation will increase. Up to now there are no results from randomized trials available whether or not, and when, ICH survivors should resume OAC. This review summarizes the most important observational studies, and initiated ongoing trials, to help guiding physicians in daily routine decision making. Findings: Several large observational studies and meta-analyses verified that OAC resumption was associated with a significant reduction of thromboembolic complications and mortality without leading to increased rates of recurrent ICH. OAC resumption seemed further associated with improved functional recovery and favorable long-term outcome. Given the general bleeding risk reduction in patients using Non–vitamin K antagonist oral anticoagulants (NOAC) compared to Vitamin-K-antagonist (VKA), NOAC use should also be preferred after ICH, although specific comparative studies are pending. Patients with lobar ICH need special attention as these patients showed increased ICH recurrence rates, why decision making should include extended diagnostic work-up evaluating cerebral microbleed burden, cortical subarachnoid hemorrhage and superficial siderosis. Further, patients with mechanical heart valves need specific consideration as restarting VKA may be unsafe until two weeks, whereas optimal balancing of hemorrhagic with thromboembolic complications may allow earlier re-initiation one week after ICH. In patients with atrial fibrillation, resumption generally should take place between 4 and 8 weeks after ICH depending on a patient’s individual risk profile. Left atrial appendage occlusion (LAAO) might represent an alternative strategy in high-risk patients. Ongoing clinical trials will clarify whether OAC resumption versus LAAO versus no antithrombotic therapy may represent the best possible secondary stroke prevention in ICH survivors with atrial fibrillation. Conclusions: According to observational data OAC resumption after ICH seems beneficial and safe. Ongoing clinical trials will create evidence regarding treatment effects of pharmaceutical resumption and interventional alternatives. Yet, individual decision making weighing the patient’s individual thromboembolic versus hemorrhagic risks remains essential.
CRIS-Team Scopus Importer:2024-12-16
Keywords: Intracerebral hemorrhage; Intracranial hemorrhage; Oral anticoagulation; Resumption; Secondary prophylaxis; Stroke prevention

Retention, dosing, tolerability and patient reported seizure outcome of Zonisamide as only add-on treatment under real-life conditions in adult patients with partial onset seizures: Results of the observational study ZOOM - Hamer, Hajo; Baulac, Michel; Mcmurray, Rob; Kockelmann, Edgar (Seizure-European Journal of Epilepsy, 2016)
Zonisamide is licensed for adjunctive therapy for partial-onset seizures with or without secondary generalisation in patients 6 years and older and as monotherapy for the treatment of partial seizures in adult patients with newly diagnosed epilepsy, and shows a favourable pharmacokinetic profile with low interaction potential with other drugs. The aim of the present study was to gather real-life data on retention and modalities of zonisamide use when administered as only add-on treatment to a current AED monotherapy in adult patients with partial-onset seizures.This multicenter observational study was performed in 4 European countries and comprised three visits: baseline, and after 3 and 6 months. Data on patients' retention, reported efficacy, tolerability and safety, and quality of life was collected. Of 100 included patients, 93 could be evaluated.After 6 months, the retention rate of zonisamide add-on therapy was 82.8%. At this time, a reduction of seizure frequency of at least 50% was observed in 79.7% of patients, with 43.6% reporting seizure freedom over the last 3 months of the study period. Adverse events were reported by 19.4% of patients, with fatigue, agitation, dizziness, and headache being most frequent. Approximately 25% of patients were older than 60 years, many of whom suffered from late-onset epilepsy. Compared to younger patients, these patients showed considerable differences with regard to their antiepileptic drug regimen at baseline, and slightly higher responder and retention rates at 6 months.Despite limitations due to the non-interventional open-label design and the low sample size, the results show that zonisamide as only add-on therapy is well retained, indicating effectiveness in the majority of patients under real-life conditions.
EVALuna2:22377

Retinal imaging and axonal degeneration in later onset multiple sclerosis - Huhn, Konstantin; Lämmer, Robert; Meng, Hanna Zimmermann; Laemmer, Alexandra; Waschbisch, Anne; Utz, Kathrin; Giess, Rene Markus; Paul, Friedemann; Linker, Ralf; Lee, De-Hyung (Journal of the Neurological Sciences, 2016)
Multiple Sclerosis (MS) is a chronic inflammatory disease of the CNS typically affecting younger adults and resulting in neuro-axonal degeneration already at early stages of the disease. Less is known about the effects of a later disease onset (LOMS, onset >50years of age). Analysis of retinal layers by optical coherence tomography (OCT) is a non-invasive method to investigate retinal and neuro-axonal degeneration. We applied OCT to detect differences in retinal damage depending on a later disease manifestation.14 LOMS patients, 14 age- and 14 disease duration-matched normal onset (NOMS) patients with a relapsing remitting disease course and 15 healthy controls (HC) were included. OCT measurement of peripapillary retinal nerve fiber layer (RNFL), total macular volume (TMV), combined ganglion cell/inner plexiform layer (GCIPL), inner nuclear layer (INL) and outer retinal layers (ORL) was conducted. Furthermore, analysis of clinical features and of effects of previous optic neuritis (ON) was performed RESULTS: In a GEE based analysis of age- and disease duration matched NOMS, LOMS patients show no significant differences in retinal layer thickness whereas ON significantly reduced thickness of retinal layers. All MS groups display lower retinal layer thickness as compared to HC independently of type of onset.Our LOMS findings are well in line with published OCT data of normal onset MS. As the degree of retinal layer thinning was similar in MS subgroups, retinal neurodegeneration in MS may occur independently of time of disease onset.
EVALuna2:21282