Can flat-detector CT after successful endovascular treatment predict long-term outcome in patients with large vessel occlusion? An Alberta Stroke Programme Early CT Score–based study - Knott, Michael; Hölter, Philip; Hock, Stefan; Mühlen, Iris; Gerner, Stefan; Sprügel, Maximilian; Huttner, Hagen; Schwab, Stefan; Engelhorn, Tobias; Dörfler, Arnd (Neurological Sciences, 2022)
Purpose: Recent studies postulate a high prognostic value of the Alberta Stroke Programme Early CT Score (ASPECTS) applied on non-contrast whole-brain flat-detector CT (FDCT) after successful endovascular treatment (EVT). The aim of this study was the evaluation of long-term patient outcome after endovascular treatment using postinterventional FDCT. Methods: Using a local database (Stroke Research Consortium in Northern Bavaria, STAMINA), 517 patients with successful endovascular treatment (modified Thrombolysis in Cerebral Infarction (mTICI) ≥ 2B) due to acute ischaemic stroke (AIS) and large vessel occlusion (LVO) of the anterior circulation were recruited retrospectively. In all cases, non-contrast FDCT after EVT was analysed with special focus at ASPECTS. These results were correlated with the functional outcome in long-term (modified Rankin Scale (mRS) shift from pre-stroke to 90 days after discharge). Results: A significant difference in FDCT-ASPECTS compared to the subgroup of favourable vs. unfavourable outcome (Δ mRS) (median ASPECTS 10 (10–9) vs. median ASPECTS 9 (10–7); p = 0,001) could be demonstrated. Multivariable regression analysis revealed FDCT-ASPECTS (OR 0.234, 95% CI − 0.102–0.008, p = 0.022) along with the NHISS at admission (OR 0.169, 95% CI 0.003–0.018, p = 0.008) as independent factors for a favourable outcome. Cut-off point for a favourable outcome (Δ mRS) was identified at an ASPECTS ≥ 8 (sensitivity 90.6%, specificity 35%). Conclusion: For patients with LVO and successful EVT, FDCT-ASPECTS was found to be highly reliable in predicting long-term outcome.
CRIS-Team Scopus Importer:2022-12-02
Keywords: ASPECTS; Endovascular treatment; Flat-detector CT; Stroke

Can stapedius reflex testing objectively measure muscle function in Pompe patients? - Hilz, Max-Josef; Hoppe, Ulrich; Möller, Sebastian; Wang, Ruihao; Koehn, Julia (Clinical Case Reports, 2015)
We assessed the value of stapedius reflex testing as an objective measurement of striated muscle function in four patients with Pompe disease. Common tests of disease severity and efficacy of enzyme replacement therapy (ERT) yield highly variable results that depend on patient cooperation and day-to-day performance, whereas stapedius reflex thresholds improved in seven of eight ears after 2 years of ERT.
EVALuna2:19973

Can we predict cognitive decline after initial diagnosis of multiple sclerosis? Results from the German National early MS cohort (KKNMS) - Johnen, Andreas; Buerkner, Paul-Christian; Landmeyer, Nils C.; Ambrosius, Bjoern; Calabrese, Pasquale; Motte, Jeremias; Hessler, Nicole; Antony, Gisela; Koenig, Inke R.; Klotz, Luisa; Hoshi, Muna-Miriam; Aly, Lilian; et al. (Journal of Neurology, 2019)
BackgroundCognitive impairment (CI) affects approximately one-third of the patients with early multiple sclerosis (MS) and clinically isolated syndrome (CIS). Little is known about factors predicting CI and progression after initial diagnosis.MethodsNeuropsychological screening data from baseline and 1-year follow-up of a prospective multicenter cohort study (NationMS) involving 1123 patients with newly diagnosed MS or CIS were analyzed. Employing linear multilevel models, we investigated whether demographic, clinical and conventional MRI markers at baseline were predictive for CI and longitudinal cognitive changes.ResultsAt baseline, 22% of patients had CI (impairment in 2 cognitive domains) with highest frequencies and severity in processing speed and executive functions. Demographics (fewer years of academic education, higher age, male sex), clinical (EDSS, depressive symptoms) but no conventional MRI characteristics were linked to baseline CI. At follow-up, only 14% of patients showed CI suggesting effects of retesting. Neither baseline characteristics nor initiation of treatment between baseline and follow-up was able to predict cognitive changes within the follow-up period of 1 year.ConclusionsIdentification of risk factors for short-term cognitive change in newly diagnosed MS or CIS is insufficient using only demographic, clinical and conventional MRI data. Change-sensitive, re-test reliable cognitive tests and more sophisticated predictors need to be employed in future clinical trials and cohort studies of early-stage MS to improve prediction.
CRIS-Team WoS Importer:2019-02-21

Cardiac stunning as first manifestation of multiple sclerosis: A case report reminding us not to overlook cardiovascular autonomic dysfunction in multiple sclerosis - Hilz, Max-Josef (Multiple sclerosis journal, 2016)
Autonomic dysfunction is common but frequently overlooked in multiple sclerosis (MS) patients. The case of a Tako-Tsubo cardiomyopathy on which this commentary is based shows that centrally triggered autonomic dysfunction may be the first life-threatening manifestation of MS.
EVALuna2:22462

Cardioembolic Stroke Risk and Recovery After Anticoagulation-Related Intracerebral Hemorrhage - Murphy, Meredith P.; Kuramatsu, Joji; Leasure, Audrey; Falcone, Guido J.; Kamel, Hooman; Sansing, Lauren H.; Kourkoulis, Christina; Schwab, Kristin; Elm, Jordan J.; Gurol, M. Edip; Huy Tran,; Greenberg, Steven M.; et al. (Stroke, 2018)
Background and Purpose- Whether to resume oral anticoagulation treatment after intracerebral hemorrhage (ICH) remains an unresolved question. Previous studies focused primarily on recurrent stroke after ICH. We sought to investigate the association between cardioembolic stroke risk, oral anticoagulation therapy resumption, and functional recovery among ICH survivors in the absence of recurrent stroke. Methods- We conducted a joint analysis of 3 observational studies: (1) the multicenter RETRACE study (German-Wide Multicenter Analysis of Oral Anticoagulation Associated Intracerebral Hemorrhage); (2) the Massachusetts General Hospital ICH study (n=166); and (3) the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage; n=131). We included 941 survivors of ICH in the setting of active oral anticoagulation therapy for prevention of cardioembolic stroke because of nonvalvular atrial fibrillation and without evidence of ischemic stroke and recurrent ICH at 1 year from the index event. We created univariable and multivariable models to explore associations between cardioembolic stroke risk (based on CHA2DS2-VASc scores) and functional recovery after ICH, defined as achieving modified Rankin Scale score of ≤3 at 1 year for participants with modified Rankin Scale score of >3 at discharge. Results- In multivariable analyses, the CHA2DS2-VASc score was associated with a decreased likelihood of functional recovery (odds ratio, 0.83 per 1 point increase; 95% CI, 0.79-0.86) at 1 year. Anticoagulation resumption was independently associated with a higher likelihood of recovery, regardless of CHA2DS2-VASc score (odds ratio, 1.89; 95% CI, 1.32-2.70). We found an interaction between CHA2DS2-VASc score and anticoagulation resumption in terms of association with increased likelihood of functional recovery (interaction P=0.011). Conclusions- Increasing cardioembolic stroke risk is associated with a decreased likelihood of functional recovery at 1 year after ICH, but this association was weaker among participants resuming oral anticoagulation therapy. These findings support, including recovery metrics, in future studies of anticoagulation resumption after ICH.
EVALuna2:34937

Cardiovagal responses to autonomic challenges are reduced after six months of Fingolimod-therapy in patients with multiple sclerosis - de Rojas Leal, Carmen; Wang, Ruihao; Roy, Sankanika; Liu, Mao; Canavese, F.; Hoesl, K.; Winder, K.; Lee, De-Hyung; Linker, Ralf; Hilz, M. J. (2017)
EVALuna2:22569

Cardiovascular autonomic dysfunction: A cause of acute COVID-19 complications and persistent post-COVID-19 complaints? - Hilz, Max-Josef (European Journal of Neurology, 2023)
CRIS-Team Scopus Importer:2023-02-24

Cardiovascular autonomic dysfunction in patients with posterior circulation ischemic stroke - Wang, Ruihao; Macha, Kosmas; Koehn, Julia; Siedler, Gabriela; Winder, Klemens; Gerner, Stefan; Schwab, Stefan; Kohrmann, Martin; Hilz, Max-Josef; Kallmünzer, Bernd (JOURNAL OF THE NEUROLOGICAL SCIENCES, 2021)
CRIS-Team WoS Importer:2021-12-03

CARDIOVASCULAR AUTONOMIC MODULATION THREE MONTHS POST STROKE IMPROVES IN PATIENTS WITH ISCHEMIA IN THE RIGHT MIDDLE CEREBRAL ARTERY TERRITORY - Wang, Ruihao; Macha, Kosmas; Köhn, Julia; Marsch, Armin; Winder, Klemens; Gerner, Stefan; Koehrmann, M.; Schwab, Stefan; Kallmünzer, Bernd; Hilz, Max-Josef (INTERNATIONAL JOURNAL OF STROKE, 2020)
CRIS-Team WoS Importer:2021-01-22

Cardiovascular autonomic regulation correlates with cognitive performance in patients with a history of traumatic brain injury - Wang, Ruihao; Muresanu, Dafin; Hösl, Katharina; Hilz, Max-Josef (Neurological Sciences, 2023)
Background and objective: Traumatic brain injury (TBI) may afflict brain areas contributing to both cardiovascular autonomic regulation and cognitive performance. To evaluate possible associations between both functions in patients with a history of TBI (post-TBI-patients), we determined correlations between cardiovascular autonomic regulation and cognitive function in post-TBI-patients. Methods: In 86 post-TBI-patients (33.1 ± 10.8 years old, 22 women, 36.8 ± 28.9 months after injury), we monitored RR intervals (RRI), systolic and diastolic blood pressures (BPsys, BPdia), and respiration (RESP) at rest. We calculated parameters of total cardiovascular autonomic modulation (RRI-standard-deviation (RRI-SD), RRI-coefficient-of-variation (RRI-CV), RRI-total-powers), sympathetic (RRI-low-frequency-powers (RRI-LF), normalized (nu) RRI-LF-powers, BPsys-LF-powers) and parasympathetic modulation (root-mean-square-of-successive-RRI-differences (RMSSD), RRI-high-frequency-powers (RRI-HF), RRI-HFnu-powers), sympathetic-parasympathetic balance (RRI-LF/HF-ratios), and baroreflex sensitivity (BRS). We used the Mini-Mental State Examination and Clock Drawing Test (CDT) to screen the general global and visuospatial cognitive function, and applied the standardized Trail Making Test (TMT)-A assessing visuospatial abilities and TMT-B assessing executive function. We calculated correlations between autonomic and cognitive parameters (Spearman’s rank correlation test; significance: P < 0.05). Results: CDT values positively correlated with age (P = 0.013). TMT-A values inversely correlated with RRI-HF-powers (P = 0.033) and BRS (P = 0.043), TMT-B values positively correlated with RRI-LFnu-powers (P = 0.015), RRI-LF/HF-ratios (P = 0.036), and BPsys-LF-powers (P = 0.030), but negatively with RRI-HFnu-powers (P = 0.015). Conclusions: In patients with a history of TBI, there is an association between decreased visuospatial and executive cognitive performance and reduced parasympathetic cardiac modulation and baroreflex sensitivity with relatively increased sympathetic activity. Altered autonomic control bears an increased cardiovascular risk; cognitive impairment compromises quality of life and living conditions. Thus, both functions should be monitored in post-TBI-patients.
CRIS-Team Scopus Importer:2023-07-07
Keywords: Cardiovascular autonomic regulation; Cognitive performance; Correlations; Executive function; Traumatic brain injury; Visuospatial function

Cardiovascular fingolimod effects on rapid baroreceptor unloading are counterbalanced by baroreflex resetting - Hilz, Max-Josef; Roy, Sankanika; de Rojas Leal, Carmen; Liu, Mao; Canavese, Francesca; Winder, Klemens; Hoesl, Katharina M.; Lee, De Hyung; Linker, Ralf A.; Wang, Ruihao (Neurological Sciences, 2021)
Background and purpose: Initial cardiovascular fingolimod effects might compromise baroreflex responses to rapid blood pressure (BP) changes during common Valsalva-like maneuvers. This study evaluated cardiovascular responses to Valsalva maneuver (VM)-induced baroreceptor unloading and loading upon fingolimod initiation. Patients and methods: Twenty-one patients with relapsing-remitting multiple sclerosis performed VMs before and 0.5, 1, 2, 3, 4, 5, and 6 hours after fingolimod initiation. We recorded heart rate (HR) as RR intervals (RRI), systolic and diastolic BP (BPsys, BPdia) during VM phase 1, VM phase 2 early, VM phase 2 late, and VM phase 4. Using linear regression analysis between decreasing BPsys and RRI values during VM phase 2 early, we determined baroreflex gain (BRG) reflecting vagal withdrawal and sympathetic activation upon baroreceptor unloading. To assess cardiovagal activation upon baroreceptor loading, we calculated Valsalva ratios (VR) between maximal and minimal RRIs after strain release. Analysis of variance or Friedman tests with post hoc analysis compared corresponding parameters at the eight time points (significance: p < 0.05). Results: RRIs at VM phase 1, VM phase 2 early, and VM phase 2 late were higher after than before fingolimod initiation, and maximal after 4 hours. Fingolimod did not affect the longest RRIs upon strain release, but after 3, 5, and 6 hours lowered the highest BPsys values during overshoot and all BPdia values, and thus reduced VRs. BRG was slightly higher after 3 and 5 hours, and significantly higher after 4 hours than before fingolimod initiation. Conclusions: VR-decreases 3–6 hours after fingolimod initiation are physiologic results of fingolimod-associated attenuations of BP and HR increases at the end of strain and do not suggest impaired cardiovagal activation upon baroreceptor loading. Stable and at the time of HR nadir significantly increased BRGs indicate improved responses to baroreceptor unloading. Thus, cardiovascular fingolimod effects do not impair autonomic responses to sudden baroreceptor loading or unloading but seem to be mitigated by baroreflex resetting.
CRIS-Team Scopus Importer:2021-01-29
Keywords: Baroreflex gain; Baroreflex resetting; Cardiovascular fingolimod effects; Multiple sclerosis; Valsalva maneuver

Cardiovascular medication seems to promote recovery of autonomic dysfunction after stroke - Wang, Ruihao; Koehrmann, Martin; Kollmar, Rainer; Köhn, Julia; Schwab, Stefan; Kallmünzer, Bernd; Hilz, Max-Josef (Journal of Neurology, 2022)
Background Stroke may compromise cardiovascular-autonomic modulation (CAM). The longitudinal post-stroke CAM alterations remain unclear as previous studies excluded patients with cardiovascular medication. This study evaluated whether CAM dysfunction improves after several months in patients under typical clinical conditions, i.e., without excluding patients with cardiovascular medication. Methods In 82 ischemic stroke patients [33 women, 64.9 +/- 8.9 years, NIHSS-scores 2 (interquartile range 1-5)], we evaluated the applications of cardiovascular medication before stroke, during autonomic tests performed within 1 week, 3 and 6 months after stroke onset. We determined resting RR intervals (RRI), systolic, diastolic blood pressures (BPsys), respiration, parameters reflecting total CAM [RRI-standard deviation (RRI-SD), RRI-total powers], sympathetic [RRI-low-frequency powers (RRI-LF), BPsys-LF powers] and parasympathetic CAM [RMSSD, RRI-high-frequency powers (RRI-HF powers)], and baroreflex sensitivity. ANOVA or Friedman tests with post hoc analyses compared patient data with data of 30 healthy controls, significance was assumed for P < 0.05. Results More patients had antihypertensive medication after than before stroke. First-week CAM testing showed lower RRIs, RMSSD, RRI-SDs, RRI-total powers, RRI-HF powers, and baroreflex sensitivity, but higher BPsys-LF powers in patients than controls. After 3 and 6 months, patients had significantly higher RRIs, RRI-SDs, RRI-total powers, RMSSDs, RRI-HF powers, and baroreflex sensitivity, but lower BPsys-LF powers than in the 1st week; RMSSDs and RRI-HF powers no longer differed between patients and controls. However, 6-month values of RRIs, RRI-SDs, and baroreflex sensitivity were again lower in patients than controls. Conclusions Even mild strokes compromised cardiovagal modulation and baroreflex sensitivity. After 3 months, CAM had almost completely recovered. Recovery might be related to the mild stroke severity. Presumably, CAM recovery was also promoted by the increased application of cardiovascular medication. Yet, slight CAM dysfunction after 6 months suggests continuing autonomic vulnerability.
CRIS-Team WoS Importer:2022-06-24

Case report: Cerebrospinal fluid neutrophilic pleocytosis upon intrathecal triamcinolone injection - Tsaktanis, Thanos; Stritzelberger, Jenny; To, Vi Tuong Daniel; Uhl, Martin; Schwab, Stefan; Heuß, Dieter Felix; Rothhammer, Veit (Frontiers in Neurology, 2024)
Intrathecal corticosteroids, initially employed in the 1950s, faced declining use due to complications like arachnoiditis and aseptic meningitis. Triamcinolone, which is nowadays used as intrathecally applied glucocorticoid formulation, has been shown to beneficially influence spasticity without demonstrable influence on disease activity or progression. We here present the case of a patient with recurrent episodes of aseptic cerebrospinal fluid (CSF) neutrophilic pleocytosis over a year following intrathecal triamcinolone treatment. CSF analyses revealed a post-injection CSF cytokine profile resembling cytokine release reaction rather than drug hypersensitivity. This case thus highlights a potential side effect of intrathecal triamcinolone injection with yet unclear clinical relevance, underscores the need for further assessment of clinical benefits of intrathecal triamcinolone, and emphasizes potential short and long-term side effects associated with extended intrathecal triamcinolone use.
CRIS-Team Scopus Importer:2024-05-24
Keywords: chemical meningitis; inflammatory CSF syndrome; intrathecal injection of triamcinolone; side effect; spasticity; triamcinolone

Cavernoma-related epilepsy: Review and recommendations for management - Report of the Surgical Task Force of the ILAE Commission on Therapeutic Strategies - Rosenow, Felix; Alonso-Vanegas, Mario A.; Baumgartner, Christoph; Blümcke, Ingmar; Carreno, Maria; Gizewski, Elke R.; Hamer, Hajo; Knake, Susanne; Kahane, Philippe; Lueders, Hans O.; Mathern, Gary W.; Menzler, Katja; et al. (Epilepsia, 2013)
Cerebral cavernous malformations (CCMs) are well-defined, mostly singular lesions present in 0.4-0.9% of the population. Epileptic seizures are the most frequent symptom in patients with CCMs and have a great impact on social function and quality of life. However, patients with CCM-related epilepsy (CRE) who undergo surgical resection achieve postoperative seizure freedom in only about 75% of cases. This is frequently because insufficient efforts are made to adequately define and resect the epileptogenic zone. The Surgical Task Force of the Commission on Therapeutics of the International League Against Epilepsy (ILAE) and invited experts reviewed the pertinent literature on CRE. Definitions of definitive and probable CRE are suggested, and recommendations regarding the diagnostic evaluation and etiology-specific management of patients with CRE are made. Prospective trials are needed to determine when and how surgery should be done and to define the relations of the hemosiderin rim to the epileptogenic zone.© 2013 International League Against Epilepsy.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Cavernous hemangioma; Epilepsy surgery; Etiology; Outcome; Risk factors

CD133-Positive Membrane Particles in Cerebrospinal Fluid of Patients with Inflammatory and Degenerative Neurological Diseases - Bobinger, Tobias; May, Lisa-Sophie; Lücking, Hannes; Kloska, Stephan; Burkardt, Petra; Spitzer, Philipp; Maler, Juan M.; Corbeil, Denis; Huttner, Hagen (Frontiers in Cellular Neuroscience, 2017)
Background: Analysis of cerebrospinal fluid (CSF) is a frequently used diagnostic tool in a variety of neurological diseases. Recent studies suggested that investigating membrane particles enriched with the stem cell marker CD133 may offer new avenues for studying neurological disease. In this study, we evaluated the amount of membrane particle-associated CD133 in human CSF in neuroinflammatory and degenerative diseases. Methods: We compared the amount of membrane particle-associated CD133 in CSF samples collected from 45 patients with normal pressure hydrocephalus, parkinsonism, dementia, and cognitive impairment, chronic inflammatory diseases and 10 healthy adult individuals as controls. After ultracentrifugation of CSF, gel electrophoresis and immunoblotting using anti-CD133 monoclonal antibody 80B258 were performed. Antigen-antibody complexes were detected using chemiluminescence. Results: The amount of membrane particle-associated CD133 was significantly increased in patients with normal pressure hydrocephalus (p < 0.001), parkinsonism (p = 0.011) as well as in patients with chronic inflammatory disease (p = 0.008). Analysis of CSF of patients with dementia and cognitive impairment revealed no significant change compared with healthy individuals. Furthermore, subgroup analysis of patients with chronic inflammatory diseases demonstrated significantly elevated levels in individuals with relapsing-remitting multiple sclerosis (p = 0.023) and secondary progressive multiple sclerosis (SPMS; p = 0.010). Conclusion: Collectively, our study revealed elevated levels of membrane particle-associated CD133 in patients with normal pressure hydrocephalus, parkinsonism as well as relapsing-remitting and SPMS. Membrane glycoprotein CD133 may be of clinical value for several neurological diseases.
EVALuna2:22515

Cécile and Oskar Vogt: their life, work, and contribution to epileptology Cécile & Oskar Vogt: Leben, Werk und ihr Beitrag zur Epileptologie - Kasper, Burkhard S. (Clinical Epileptology, 2025)
Cécile and Oskar Vogt were brain researchers who systematically investigated the structure and function of the central nervous system together over decades. At the turn of the century in Berlin, even before 1900, they started their cytoarchitectonic and myeloarchitectonic studies using whole brain sections and began performing cortical stimulation experiments in different species, which they continued until their death. With the restricted resources of a private Berlin flat, they started their “Neurology Central Station,” which became the university neurology laboratory in 1902 and the Kaiser Wilhelm Institute (KWI) for brain research in 1914. As late as 1931, they moved into a newly built modern KWI at Buch in Berlin. This KWI represented the first institute of its kind worldwide, made possible by generous support from the Krupp family and the Rockefeller Foundation. Removed from the Berlin institute by the Nazi regime, they built a new institute in the black forest. Their legacy today is saved and continued by the Cécile and Oskar Vogt Institute for Brain Research in Düsseldorf, Germany. As part of the Vogt group, Korbinian Brodmann developed his famous cytoarchitectonic map. They discussed their cortical stimulation results and compared them to those of Otfrid Foerster and Wilder Penfield, among others. The Vogts worked on abundant topics. Although they did not study epilepsy explicitly, Ammon’s horn sclerosis (AHS) represented a central lesion in their work, for the Vogts observed “selective vulnerability of brain regions” and explained this by their theory of pathoclisis. Selective vulnerability was discussed controversially for AHS in epilepsy, but turned out to be quite correct, although the Vogts were not able to prove their concept given the methods of the time. Many of Cécile and Oskar Vogt’s results still have an impact today and represent an important fundament of modern epileptology.
CRIS-Team Scopus Importer:2025-05-09
Keywords: Architectonic; Cécile Vogt; History of epileptology; Oskar Vogt; Pathoclisis

Cellular plasticity and myeloid inflammation in the adult brain are independent of the transcriptional modulator DREAM - Masanetz, Rebecca Katharina; Baum, Wolfgang; Schett, Georg; Winkler, Jürgen; Süß, Patrick (Neuroscience Letters, 2023)
The downstream regulatory element antagonist modulator (DREAM) modulates ion channel function and gene transcription. Functionally, DREAM is implicated in physiological and pathological processes including cell proliferation, inflammation, and nociception. Despite its multiple functions and robust expression in forebrain tissue, neurons and glial cells, the role of DREAM in regard to cellular plasticity and tumor necrosis factor (TNF)-mediated inflammation is largely unexplored. Here, we demonstrate that adult hippocampal neurogenesis as well as the density and plasticity of glial cells in the hippocampus and thalamus are independent of the presence of DREAM. Further, DREAM deletion does not alter the regional myeloid response and inflammatory gene expression induced by chronic peripheral inflammation in mice overexpressing human TNF. Our data suggest that despite their highly dynamic regulation, neural cell plasticity and adult neurogenesis in the hippocampus do not depend on the multifunctional protein DREAM. Furthermore, TNF-mediated myeloid inflammation in the brain persists in the absence of DREAM.
CRIS-Team Scopus Importer:2023-01-20
Keywords: Adult hippocampal neurogenesis; DREAM; Glia; Neuroinflammation; Pain; Proliferation

Cellular repair strategies in Parkinson's disease - Winner, Beate; Vogt Weisenhorn, Daniela M.; Lie, Chichung D.; Blümcke, Ingmar; Winkler, Jürgen (Therapeutic Advances in Neurological Disorders, 2009)
Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting 0.7% of the elderly population (defined as over 65 years of age). PD is clinically characterized by resting tremor, muscular rigidity, hypokinesia and postural instability. These motor symptoms result largely from the deficiency or dysfunction of dopaminergic neurons in the substantia nigra. Histopathological analysis reveals depletion of dopaminergic neurons as well as eosinophilic intracytoplasmic inclusions (Lewy bodies) in surviving neurons of the substantia nigra and other brain regions. The molecular pathogenesis is linked to protein misfolding by compromised alpha-synuclein and/or related proteins (synucleinopathy). Therefore, successful therapy of motor symptoms aims for the restoration of dopaminergic neurotransmission. Pharmacological drug treatment is usually effective only at an early stage of the disease but cannot halt progressive neuronal degeneration. With recent developments in stem cell technology, cell repair or replacement approaches came into focus. Here, we review new therapeutic strategies resulting from the innate propensity of the adult brain to generate new neurons, either by pharmacological stimulation of endogenous adult stem cell population or exogenous cell transplantation modalities. © 2009, SAGE Publications. All rights reserved.
CRIS-Team Scopus Importer:2024-08-07
Keywords: Alpha-synuclein; Neurodegeneration; Neurogenesis; Stem cells; Transplantation

Cellular replacement strategies and adult neurogenesis in idiopathic Parkinson's disease - Marxreiter, Franz; Storch, A.; Winkler, Jürgen (Der Nervenarzt, 2016)
Parkinson's disease (PD) is the most common age-related movement disorder and characterized by slowly progressive neurodegeneration resulting in motor symptoms, such as bradykinesia, rigidity, tremor and postural instability. Moreover, non-motor symptoms, such as hyposmia, anxiety and depression reduce the quality of life in PD. Motor symptoms are associated with a distinct striatal dopaminergic deficit resulting from axonal dysfunction and neuronal loss in the substantia nigra (SN). Recent progress in stem cell technology allows the optimization of cellular transplantation strategies in order to alleviate the motor deficit, which potentially leads to a reactivation of this therapeutic strategy. Besides neurodegenerative processes impaired adult neurogenesis and consequentially reduced endogenous cellular plasticity may play an important role in PD. This article discusses the notion that non-motor symptoms in PD may partly be explained by reduced adult neurogenesis in the olfactory bulb and hippocampus.
EVALuna2:33516

Central Autonomic Dysfunction Delays Recovery of Fingolimod Induced Heart Rate Slowing - Hilz, Max-Josef; Intravooth, Tassanai; Möller, Sebastian; Wang, Ruihao; Lee, De-Hyung; Koehn, Julia; Linker, Ralf (PLoS ONE, 2015)
In multiple sclerosis (MS) patients, Fingolimod may induce prolonged heart-rate slowing which might be caused by MS-related central autonomic lesions.To evaluate whether MS-patients with prolonged heart-rate slowing (> six hours) upon Fingolimod show cardiovascular-autonomic dysfunction before Fingolimod-initiation.Before Fingolimod-initiation, we recorded electrocardiographic RR-intervals (RRIs) and blood-pressure (BP) at rest, upon standing-up, during metronomic deep-breathing, Valsalva-maneuver, and "sustained-handgrip-exercise" in 21 patients with relapsing-remitting MS, and 20 healthy persons. We calculated sympathetic and parasympathetic cardiovascular parameters, including low- (LF) and high-frequency (HF) powers of RRI- and BP-oscillations, RRI-RMSSDs, RRI- and BP-changes during handgrip-exercise, parasympathetic heart-rate-slowing in relation to BP-overshoot after Valsalva-strain-release. We compared values of healthy persons and patients with and without prolonged heart-rate slowing after Fingolimod-initiation (ANOVA; significance: p<0.05).Upon Fingolimod-initiation, 7/21 patients had prolonged HR-slowing. Before Fingolimod, these patients had higher resting BP and higher BP increase during handgrip-exercise than had the other participants (p<0.05). They did not reduce parasympathetic HR-parameters upon standing-up. After Valsalva-strain-release, their parasympathetic HR-slowing in response to BP-overshoot was four times higher than in the other participants (p<0.05).The autonomic cardiovascular dysfunction in MS-patients with delayed HR-re-acceleration upon Fingolimod-initiation suggests that MS-related central autonomic lesions compromise HR-re-acceleration upon Fingolimod.German Clinical Trial Register DRKS00004548 http://drks-neu.uniklinik-freiburg.de/drks_web/setLocale_EN.do.
EVALuna2:22339

Cerebral aneurysm treatment using flow-diverting stents: in-vivo visualization of flow alterations by parametric colour coding to predict aneurysmal occlusion: preliminary results - Gölitz, Philipp; Struffert, Tobias; Roesch, Julie; Ganslandt, Oliver Thomas; Knossalla, Frauke; Dörfler, Arnd (European Radiology, 2015)
After deployment of flow-diverting stents (FDS), complete aneurysm occlusion is not predictable. This study investigated whether parametric colour coding (PCC) could allow in vivo visualization of flow alterations induced by FDS and identify favourable or adverse flow modulations.Thirty-six patients treated by FDS were analyzed. Preinterventional and postinterventional DSA-series were postprocessed by PCC and time-density curves (TDCs) were calculated. The parameters aneurysmal inflow, outflow, and relative time-to-peak (rTTP) were calculated. Preinterventional and postinterventional values were compared and related to occlusion rate.Postinterventional inflow showed a mean reduction of 37%, outflow of 51%, and rTTP a prolongation of 82%. Saccular aneurysm occlusion occurred if a reduction of at least 15% was achieved for inflow and 35% for outflow (sensitivity: 89%, specificity: 82%). Unchanged outflow and a slightly prolonged rTTP were associated with growth in one fusiform aneurysm.PCC allows visualization of flow alterations after FDS treatment, illustrating "flow diverting effects" by the TDC shape and indicating mainly aneurysmal outflow and lesser inflow changes. Quantifiable parameters (inflow, outflow, rTTP) can be obtained, thresholds for predicting aneurysm occlusion determined, and adverse flow modulations assumed. As a rapid intraprocedural tool, PCC might support the decision to implant more than one FDS.o After deployment of a flow-diverting stent, complete aneurysm occlusion is unpredictable. o Parametric colour coding offers new options for visualizing in vivo flow alterations non-invasively. o Quantifiable parameters, i.e., aneurysmal inflow/outflow can be obtained allowing prognostic stratification. o Rapid, intraprocedural application allows treatment monitoring, potentially contributing to patient safety.
EVALuna2:22356

Cerebral Ischemia in Patients on Direct Oral Anticoagulants - Macha, Kosmas; Marsch, Armin; Siedler, Gabriela; Breuer, Lorenz; Strasser, Erwin; Engelhorn, Tobias; Schwab, Stefan; Kallmünzer, Bernd (Stroke, 2019)
Background and Purpose- In patients with ischemic stroke on therapy with vitamin K antagonists, stroke severity and clinical course are affected by the quality of anticoagulation at the time of stroke onset, but clinical data for patients using direct oral anticoagulants (DOACs) are limited. Methods- Data from our registry including all patients admitted with acute cerebral ischemia while taking oral anticoagulants for atrial fibrillation between November 2014 and October 2017 were investigated. The activity of vitamin K antagonists was assessed using the international normalized ratio on admission and categorized according to a threshold of 1.7. DOAC plasma levels were measured using the calibrated Xa-activity (apixaban, rivaroxaban, and edoxaban) or the Hemoclot-assay (dabigatran) and categorized into low (<50 ng/mL), intermediate (50-100 ng/mL), or high (>100 ng/mL). Primary objective was the association between anticoagulant activity and clinical and imaging characteristics. Results- Four hundred sixty patients were included (49% on vitamin K antagonists and 51% on DOAC). Patients on vitamin K antagonists with low international normalized ratio values had higher scores on the National Institutes of Health Stroke Scale and a higher risk of large vessel occlusion on admission. For patients on DOAC, plasma levels were available in 75.6% and found to be low in 49 (27.7%), intermediate in 41 (23.2%), and high in 87 patients (49.2%). Low plasma levels were associated with higher National Institutes of Health Stroke Scale scores on admission (low: 8 [interquartile range, 3-15] versus intermediate: 4 [1-11] versus high: 3 [0-8]; P<0.001) and higher risk of persisting neurological deficits or cerebral infarction on imaging (85.7% versus 75.6% versus 54.0%; P<0.001). Low DOAC plasma levels were an independent predictor of large vessel occlusion (odds ratio, 3.84 [95% CI, 1.80-8.20]; P=0.001). Conclusions- The activity of anticoagulation measured by specific DOAC plasma levels on admission is associated with stroke severity and presence of large vessel occlusion.
CRIS-Team Scopus Importer:2019-07-19
Keywords: anticoagulants; atrial fibrillation; direct oral anticoagulants; ischemic stroke; plasma level

Cerebral lesion correlates of sympathetic cardiovascular activation in multiple sclerosis - Winder, Klemens; Linker, Ralf A.; Seifert, Frank; Wang, Ruihao; Lee, De Hyung; Engelhorn, Tobias; Dörfler, Arnd; Fröhlich, Katharina; Hilz, Max-Josef (Human Brain Mapping, 2019)
Cardiovascular autonomic dysfunction is common in multiple sclerosis (MS) and contributes significantly to disability. We hypothesized that cerebral MS-lesions in specific areas of the central autonomic network might account for imbalance of the sympathetic and parasympathetic cardiovascular modulation. Therefore, we used voxel-based lesion symptom mapping (VLSM) to determine associations between cardiovascular autonomic dysfunction and cerebral MS-related lesion sites. In 74 MS-patients (mean age 37.0 ± 10.5 years), we recorded electrocardiographic RR-intervals and systolic and diastolic blood pressure. Using trigonometric regressive spectral analysis, we assessed low (0.04–0.15 Hz) and high (0.15–0.5 Hz) frequency RR-interval-and blood pressure-oscillations and determined parasympathetically mediated RR-interval–high-frequency modulation, mainly sympathetically mediated RR-interval–low-frequency modulation, sympathetically mediated blood pressure-low-frequency modulation, and the ratios of sympathetic and parasympathetic RR-interval-modulation as an index of sympathetic-parasympathetic balance. Cerebral MS-lesions were analyzed on imaging scans. We performed a VLSM-analysis correlating parameters of autonomic dysfunction with cerebral MS-lesion sites. The VLSM-analysis showed associations between increased RR-interval low-frequency/high-frequency ratios and lesions most prominently in the left insular, hippocampal, and right frontal inferior opercular region, and a smaller lesion cluster in the right middle cerebellar peduncle. Increased blood pressure-low-frequency powers were associated with lesions primarily in the right posterior parietal white matter and again left insular region. Our data indicate associations between a shift of cardiovascular sympathetic-parasympathetic balance toward increased sympathetic modulation and left insular and hippocampal lesions, areas of the central autonomic network. The VLSM-analysis further distinguished between right inferior fronto-opercular lesions disinhibiting cardiac sympathetic activation and right posterior parietal lesions increasing sympathetic blood pressure modulation.
CRIS-Team Scopus Importer:2019-08-23
Keywords: autonomic dysfunction; insular lesion; multiple sclerosis; visceral arousal; voxel-based lesion symptom mapping

Cerebral lesions in the central pain matrix are associated with headache in multiple sclerosis - Fröhlich, Kilian; Macha, Kosmas; Siedler, Gabriela; Sekita, Alexander; Haupenthal, David; Mrochen, Anne; Wang, Ruihao; Schembs, Leah; Dörfler, Arnd; Seifert, Frank; Schwab, Stefan; Winder, Klemens (Scientific Reports, 2025)
Headache is very frequent in multiple sclerosis. However, the question whether headache is just coincidental or may be secondary due to inflammatory cerebral multiple sclerosis lesions is yet to be clarified. This study intended to evaluate the distribution of cerebral lesion sites and the potential presence of specific lesion clusters in patients with multiple sclerosis and comorbid headache using voxel-based lesion symptom mapping (VLSM). Patients with multiple sclerosis and headache were prospectively identified and included in a university neurological center between 2017 and 2023. Only patients with headache onset after first manifestation of multiple sclerosis were included. Demographic and clinical data were assessed, and lesion volumes calculated. Cerebral lesion sites were correlated voxel-wise with presence and absence of headache using non-parametric permutation testing. A cohort of multiple sclerosis patients served as controls for the VLSM-analysis. 48 multiple sclerosis patients with headache were included, as well as 92 controls without headache. Of the 48 patients with headache, 39 (81%) were female and nine (19%) were male. Mean age was significantly higher in headache patients than in controls (51 + / − 11 vs. 42 + / − 11 years, p < 0.05). EDSS, disease duration and lesion volumes did not significantly differ between both groups. Lesion overlap of all patients demonstrated a distribution of white matter lesions consistently in all subcortical brain areas. The VLSM-analysis showed associations between headache and lesion clusters in the left insula, left hippocampus and right thalamus. In our study, multiple sclerosis lesions in the left insula, left hippocampus and right thalamus were associated with headache in multiple sclerosis patients. The data therefore indicates that headache in multiple sclerosis may, in a proportion of patients, result from lesions in the central nervous systems’ pain processing network. Trial registration: No. 93_17 B, Ethics committee of the University Hospital Erlangen-Nürnberg.
CRIS-Team Scopus Importer:2025-04-01
Keywords: Cerebral lesions; Headache; Multiple sclerosis; Voxel-based lesion symptom mapping

Cerebral lesions sites in neurosarcoidosis: a lesion mapping study - Fröhlich, Kilian; Mrochen, Anne; Wang, Ruihao; Haupenthal, David; Macha, Kosmas; Siedler, Gabriela; Knott, Michael; Dörfler, Arnd; Schwab, Stefan; Winder, Klemens (Journal of Neurology, 2023)
Background and purpose: Sarcoidosis is a granulomatous disease of unknown etiology affecting the central nervous system in up to 15% of the patients. Diagnosis of neurosarcoidosis is very challenging due to the heterogeneity of its clinical manifestation. This study intended to evaluate the distribution of cerebral lesion sites and the potential presence of specific lesion clusters in neurosarcoidosis patients using voxel-based lesion symptom mapping (VLSM). Methods: Patients with neurosarcoidosis were retrospectively identified and included between 2011 and 2022. Cerebral lesion sites were correlated voxel-wise with presence and absence of neurosarcoidosis using non-parametric permutation test. Multiple sclerosis patients served as controls for the VLSM-analysis. Results: Thirty-four patients (mean age 52 ± 15 years) of whom 13 were diagnosed with possible, 19 with probable and 2 with confirmed neurosarcoidosis were identified. Lesion overlap of neurosarcoidosis patients demonstrated a distribution of white matter lesions in all brain areas, with a periventricular predilection similar to multiple sclerosis. In contrast to multiple sclerosis controls, no propensity for lesions in proximity of the corpus callosum was observed. Neurosarcoidosis lesions appeared smaller and lesion volume was lower in the neurosarcoidosis cohort. The VLSM analysis showed minor associations between neurosarcoidosis and damaged voxels in the bilateral frontobasal cortex. Conclusions: The VLSM analysis yielded significant associations in the bilateral frontal cortex, suggesting that leptomeningeal inflammatory disease with following cortical involvement is a quite specific feature in neurosarcoidosis. Lesion load was lower in neurosarcoidosis than in multiple sclerosis. However, no specific pattern of subcortical white matter lesions in neurosarcoidosis was revealed.
CRIS-Team Scopus Importer:2023-07-21
Keywords: Cerebral lesions; Neurosarcoidosis; Sarcoidosis; Voxel-based lesion symptom mapping

Cerebral lipogranuloma: A penetrating traumatic brain injury - Hagen, Manuel; Coras, Roland; Engelhorn, Tobias; Schwab, Stefan; Seifert, Frank (Neurology, 2020)
CRIS-Team Scopus Importer:2020-12-11

CEREBROSPINAL FLUID BIOMARKERS FOR CEREBRAL AMYLOID ANGIOPATHY - Sembill, Jochen; Lusse, C.; Linnerbauer, Mathias; Sprügel, Maximilian; Mrochen, Anne; Knott, Michael; Hölter, Philip; Engelhorn, Tobias; Schmidt, M.; Dörfler, Arnd; Oberstein, Timo; Maler, Juan Manuel; et al. (INTERNATIONAL JOURNAL OF STROKE, 2022)
CRIS-Team WoS Importer:2022-11-18

Cerebrospinal fluid biomarkers for cerebral amyloid angiopathy - Sembill, Jochen; Lusse, Christoph; Linnerbauer, Mathias; Sprügel, Maximilian; Mrochen, Anne; Knott, Michael; Engelhorn, Tobias; Schmidt, Manuel; Dörfler, Arnd; Oberstein, Timo; Maler, Juan Manuel; Kornhuber, Johannes; et al. (Brain Communications, 2023)
Integrating cerebrospinal fluid-biomarkers into diagnostic workup of patients with sporadic cerebral amyloid angiopathy may support early and correct identification. We aimed to identify and validate clinical- and cerebrospinal fluid-biomarkers for in vivo diagnosis of cerebral amyloid angiopathy. This observational cohort study screened 2795 consecutive patients admitted for cognitive complaints to the academic departments of neurology and psychiatry over a 10-year period (2009–2018). We included 372 patients with available hemosiderin-sensitive MR imaging and cerebrospinal fluid-based neurochemical dementia diagnostics, i.e. Aβ40, Aβ42, t-tau, p-tau. We investigated the association of clinical- and cerebrospinal fluid-biomarkers with the MRI-based diagnosis of cerebral amyloid angiopathy, applying confounder-adjusted modelling, receiver operating characteristic and unsupervised cluster analyses. We identified 67 patients with cerebral amyloid angiopathy, 76 patients with Alzheimer’s disease, 75 patients with mild cognitive impairment due to Alzheimer’s disease, 76 patients with mild cognitive impairment with unlikely Alzheimer’s disease and 78 healthy controls. Patients with cerebral amyloid angiopathy showed a specific cerebrospinal fluid pattern: average concentration of Aß40 [13 792 pg/ml (10 081–18 063)] was decreased compared to all controls (P < 0.05); Aß42 [634 pg/ml (492–834)] was comparable to Alzheimer’s disease and mild cognitive impairment due to Alzheimer’s disease (P = 0.10, P = 0.93) but decreased compared to mild cognitive impairment and healthy controls (both P < 0.001); p-tau [67.3 pg/ml (42.9–91.9)] and t-tau [468 pg/ml (275–698)] were decreased compared to Alzheimer’s disease (P < 0.001, P = 0.001) and mild cognitive impairment due to Alzheimer’s disease (P = 0.001, P = 0.07), but elevated compared to mild cognitive impairment and healthy controls (both P < 0.001). Multivariate modelling validated independent clinical association of cerebral amyloid angiopathy with older age [odds-ratio: 1.06, 95% confidence interval (1.02–1.10), P < 0.01], prior lobar intracerebral haemorrhage [14.00 (2.64–74.19), P < 0.01], prior ischaemic stroke [3.36 (1.58–7.11), P < 0.01], transient focal neurologic episodes (TFNEs) [4.19 (1.06–16.64), P = 0.04] and gait disturbance [2.82 (1.11–7.15), P = 0.03]. For cerebrospinal fluid-biomarkers per 1 pg/ml, both lower Aß40 [0.9999 (0.9998–1.0000), P < 0.01] and lower Aß42 levels [0.9989 (0.9980–0.9998), P = 0.01] provided an independent association with cerebral amyloid angiopathy controlled for all aforementioned clinical confounders. Both amyloid biomarkers showed good discrimination for diagnosis of cerebral amyloid angiopathy among adjusted receiver operating characteristic analyses (area under the receiver operating characteristic curves, Aß40: 0.80 (0.73–0.86), P < 0.001; Aß42: 0.81 (0.75–0.88), P < 0.001). Unsupervised Euclidian clustering of all cerebrospinal fluid-biomarker-profiles resulted in distinct segregation of cerebral amyloid angiopathy patients from all controls. Together, we demonstrate that a distinctive set of cerebrospinal fluid-biomarkers effectively differentiate cerebral amyloid angiopathy patients from patients with Alzheimer’s disease, mild cognitive impairment with or without underlying Alzheimer’s disease, and healthy controls. Integrating our findings into a multiparametric approach may facilitate diagnosing cerebral amyloid angiopathy, and may aid clinical decision-making, but warrants future prospective validation.
CRIS-Team Scopus Importer:2023-07-21
Keywords: biomarker; cerebral amyloid angiopathy; cerebrospinal fluid; dementia; small vessel disease

Cerebrospinal fluid microRNAs are potential biomarkers of temporal lobe epilepsy and status epilepticus - Raoof, Rana; Jimenez-Mateos, Eva M.; Bauer, Sebastian; Tackenberg, Bjoern; Rosenow, Felix; Lang, Johannes; Onugoren, Muejgan Dogan; Hamer, Hajo; Huchtemann, Tessa; Koertvelyessy, Peter; Connolly, Niamh M. C.; Pfeiffer, Shona; et al. (Scientific Reports, 2017)
There is a need for diagnostic biomarkers of epilepsy and status epilepticus to support clinical examination, electroencephalography and neuroimaging. Extracellular microRNAs may be potentially ideal biomarkers since some are expressed uniquely within specific brain regions and cell types. Cerebrospinal fluid offers a source of microRNA biomarkers with the advantage of being in close contact with the target tissue and sites of pathology. Here we profiled microRNA levels in cerebrospinal fluid from patients with temporal lobe epilepsy or status epilepticus, and compared findings to matched controls. Differential expression of 20 microRNAs was detected between patient groups and controls. A validation phase included an expanded cohort and samples from patients with other neurological diseases. This identified lower levels of miR-19b in temporal lobe epilepsy compared to controls, status epilepticus and other neurological diseases. Levels of miR-451a were higher in status epilepticus compared to other groups whereas miR-21-5p differed in status epilepticus compared to temporal lobe epilepsy but not to other neurological diseases. Targets of these microRNAs include proteins regulating neuronal death, tissue remodelling, gliosis and inflammation. The present study indicates cerebrospinal fluid contains microRNAs that can support differential diagnosis of temporal lobe epilepsy and status epilepticus from other neurological and non-neurological diseases.
EVALuna2:22535

Cerebrovascular complications of immunologically mediated heparin-induced thrombocytopenia - Macha, K.; Kloska, Stephan; Dörfler, Arnd; Raaz-Schrauder, D.; Schwab, Sibylle; Köhrmann, Martin; Seifert, Frank (Fortschritte der Neurologie - Psychiatrie, 2014)
Immunologically mediated heparin-induced thrombocytopenia (HIT) is a thrombotic disease caused by antibodies occurring after heparin exposure. Thrombocytopenia occurs within a few days after heparin exposure, about half of HIT-patients develop venous or arterial thrombotic complications. Neurological complications of HIT are mainly ischaemic stroke and sinus vein thrombosis. To ensure the primary clinical diagnosis functional and immunological assays for antibody detection are available. The probability for the occurrence of HIT depends on the nature of heparin employed (LMWH vs. UFH) and individual patient characteristics such as gender and primary disease (medical vs. surgical patients). In the case of suspected HIT heparin administration should be discontinued immediately and replaced by an alternative anticoagulation to prevent the expansion or development of further thrombotic complications. Herein we report a case of a patient suffering from HIT-associated embolic cerebral ischaemic stroke.
EVALuna2:22326

Cerebrovascular involvement in Fabry disease: current status of knowledge - Kolodny, Edwin; Fellgiebel, Andreas; Hilz, Max-Josef; Sims, Katherine; Caruso, Paul; Phan, Thanh G.; Politei, Juan; Manara, Renzo; Burlina, Alessandro (Stroke, 2015)
EVALuna2:22267

Cetuximab-Induced Aseptic Meningitis in a Patient with Colorectal Cancer: A Case Report and Review of Literature - Jäger, Jakob; Sprügel, Maximilian; Brunner, Tamara; Uhl, Martin; Schwab, Stefan; Vitali, Francesco; Wein, Axel; Volbers, Bastian (Case Reports in Neurology, 2022)
Cetuximab is a chimeric IgG1 monoclonal antibody against epidermal growth factor receptor. It is approved by the European medical agency for the treatment of RAS wild-type metastatic colorectal cancer and metastatic squamous cell cancer of the head and neck. Few cases of aseptic meningitis, primarily associated with the first administration of cetuximab in patients with squamous cell cancer, have been reported. So far, there was only 1 case in a patient with metastatic colorectal cancer. We report on a 50-year-old Caucasian patient with metastatic rectum carcinoma who suffered from headache, fever, and neck stiffness 3 h after the first administration of cetuximab (400 mg/m(2)). CSF examination revealed an excessive pleocytosis with a white blood cell count of 2,433/mu L. He was diagnosed with cetuximab-induced aseptic meningitis since clinical symptoms and CSF pleocytosis resolved within days, and further diagnostic workup revealed no infectious cause. Cetuximab-induced aseptic meningitis is a rare and severe drug reaction with predominance in treating squamous cell cancer of the head and neck. Clinical presentation and CSF findings suggest acute meningoencephalitis. In all reported cases, the course of the disease was benign and self-limited. Empiric antimicrobial and antiviral therapy are suggested until infectious causes can be ruled out. A lower dosage of cetuximab and a premedication including antihistamines and glucocorticosteroids may lower the risk of a re-occurrence if cetuximab therapy is continued.
CRIS-Team WoS Importer:2023-01-27

Changes in Gastrointestinal Microbiome Composition in PD: A Pivotal Role of Covariates - Cosma-Grigorov, Alexandra; Meixner, Holger; Mrochen, Anne; Wirtz, Stefan; Winkler, Jürgen; Marxreiter, Franz (Frontiers in Neurology, 2020)
Altered gut microbiota may trigger or accelerate alpha-synuclein aggregation in the enteric nervous system in Parkinson's disease (PD). While several previous studies observed gut microbiota alterations in PD, findings like diversity indices, and altered bacterial taxa itself show a considerable heterogeneity across studies. We recruited 179 participants, of whom 101 fulfilled stringent inclusion criteria. Subsequently, the composition of the gut microbiota in 71 PD patients and 30 healthy controls was analyzed, sequencing V3–V4 regions of the bacterial 16S ribosomal RNA gene in fecal samples. Our goal was (1) to evaluate whether gut microbiota are altered in a southern German PD cohort, (2) to delineate the influence of disease duration, stage, and motor impairment, and (3) to investigate the influence of PD associated covariates like constipation and coffee consumption. Aiming to control for a large variety of covariates, strict inclusion criteria were applied. Finally, propensity score matching was performed to correct for, and to delineate the effect of remaining covariates (non-motor symptom (NMS) burden, constipation, and coffee consumption) on microbiota composition. Prior to matching altered abundances of distinct bacterial classes, orders, families, and genera were observed. Both, disease duration, and stage influenced microbiome composition. Interestingly, levodopa equivalent dose influenced the correlation of taxa with disease duration, while motor impairment did not. Applying different statistical tests, and after propensity score matching to control for NMS burden, constipation and coffee consumption, Faecalibacterium and Ruminococcus were most consistently reduced in PD compared to controls. Taken together, similar to previous studies, alterations of several taxa were observed in PD. Yet, further controlling for PD associated covariates such as constipation and coffee consumption revealed a pivotal role of these covariates. Our data highlight the impact of these PD associated covariates on microbiota composition in PD. This suggests that altered microbiota may mediate the protective effect of i.e., coffee consumption and the negative effect of constipation in PD.
CRIS-Team Scopus Importer:2020-10-16
Keywords: biomarker; constipation; covariates; gut; microbiome; non-motor symptoms; Parkinson's disease

Changes in Immunosuppressive Treatment of Chronic Graft-versus-Host Disease: Comparison of 2 Surveys within Allogeneic Hematopoietic Stem Cell Transplant Centers in Germany, Austria, and Switzerland - Wolff, Daniel; Hilgendorf, Inken; Wagner-Drouet, Eva; Jedlickova, Zuzana; Ayuk, Francis; Zeiser, Robert; Schäfer-Eckart, Kerstin; Gerbitz, Armin; Stadler, Michael; Klein, Stefan; Middeke, Jan Moritz; Lawitschka, Anita; et al. (Biology of Blood and Marrow Transplantation, 2019)
Chronic graft-versus-host disease (cGVHD) remains the leading cause of late morbidity and mortality. Despite the growing number of treatment options in cGVHD, evidence remains sparse. The German-Austrian-Swiss GVHD Consortium performed a survey on clinical practice in treatment of cGVHD among transplant centers in Germany, Austria, and Switzerland in 2009 and 2018 and compared the results. The survey performed in 2009 contained 20 questions on first-line treatment and related issues and 4 questions on second-line scenarios followed by a survey on all systemic and topic treatment options known and applied, with 31 of 36 transplant centers (86%) responding. The survey in 2018 repeated 7 questions on first-line treatment and 3 questions on second-line scenarios followed by an updated survey on all current systemic treatment options known and applied, with 29 of 66 centers (43%) responding. In summary, the results show a large overlap of first-line treatment practice between centers and the 2 surveys because of a lack of new data that changes practice, except significant heterogeneity of treatment of cGVHD progressive onset type, which can be explained by the lack of trials focusing on this high-risk entity. In contrast, treatment options applied to second-line therapy vary considerably, with new agents like ibrutinib and ruxolitinib entering clinical practice. Moreover, treatment of bronchiolitis obliterans syndrome demonstrates heterogeneity in applied therapeutic options and sequence because of a lack of controlled data and different conclusions from already existing evidence. In summary, the survey results demonstrate an increasing number of treatment options applied to cGVHD accompanied by a significant heterogeneity in second-line treatment and underline the urgent need for clinical trials and registry analyses on rare entities with high mortality like progressive onset type and lung involvement of cGVHD.
CRIS-Team Scopus Importer:2019-05-02
Keywords: Allogeneic hematopoietic stem cell transplantation; Bone marrow transplantation; Chronic graft-versus-host disease; Immunosuppressive therapy

Changes of disease characteristics and disease-modifying treatment within one year in the National German MS cohort - Ambrosius, B.; Hessler, N.; Antony, G.; Konig, I. R.; Hoshi, M-M.; Aly, L.; Luessi, F.; Groppa, S.; Klotz, L.; Meuth, S. G.; Tackenberg, B.; Stoppe, M.; et al. (2018)
EVALuna2:201948

Characterisation of the transition area at partial hot stamped car body components by the 3-point bending test - Hezler, Christian; Kopp, C.; Bader, M.; Griesbach, B.; Merklein, Marion; Russ, F. (Proceedings SCT2011, 2011)
LFT Import::2019-08-05 (1649)

Characteristics and healthcare situation of adult patients with tuberous sclerosis complex in German epilepsy centers - Hamer, Hajo; Pfaefflin, Margarete; Baier, Hartmut; Boesebeck, Frank; Franz, Melanie; Holtkamp, Martin; Kurlemann, Gerhard; May, Theodorw.; Mayer, Thomas; Metzner, Mirjam; Steinhoff, Bernhard J.; Stodieck, Stefan; et al. (Epilepsy and Behavior, 2018)
The objective of the present study was to collect systematic data on the care of adult patients with tuberous sclerosis complex (TSC) in German epilepsy centers, to describe the characteristics of patients in this age group, and to clarify whether and how the recommended interdisciplinary care is implemented.This retrospective survey involved 12 major epilepsy centers in Germany. Aggregated data were collected based on an electronic questionnaire that addressed the sociodemographic data, characteristics of the epilepsy syndromes, and general healthcare setting of adult patients with TSC.The survey included 262 patients (mean age: 36.2±9.0years) with TSC, most of whom were reported to live in either a home for persons with a disability (37.0%), a residential care home (6.9%), or with their parents (31.1%). A further 13.0% were self-sustaining, and 8.8% were living with a partner. Most patients presented with focal (49.6%) or multifocal (33.2%) epilepsy, with complex partial, dialeptic, and automotor seizures in 66% of patients and generalized tonic-clonic seizures in 63%. Drug-refractory epilepsy was seen in 78.2% of patients, and 17.6% were seizure-free at the time of the survey. Of the 262 patients, presurgical diagnostics were performed in 27% and epilepsy surgery in 9%, which rendered 50% of these patients seizure-free. Renal screening had been performed in 56.1% within the last three years and was scheduled to be performed in 58.0%. Cases of renal angiomyolipoma were present in 46.9% of the patients. Dermatologic and pulmonary screenings were known to be planned for only few patients.Despite TSC being a multisystem disorder causing considerable impairment, every fifth adult patient is self-sustaining or living with a partner. In clinical practice, uncontrolled epilepsy and renal angiomyolipoma are of major importance in adult patients with TSC. Most patients suffer from focal or multifocal epilepsy, but epilepsy surgery is performed in less than 10% of these patients. Interdisciplinary TSC centers may help to optimize the management of patients with TSC regardless of age and ensure early and adequate treatment that also considers the advances in new therapeutic options.
EVALuna2:51820

Characteristics in Non-Vitamin K Antagonist Oral Anticoagulant-Related Intracerebral Hemorrhage - Gerner, Stefan; Kuramatsu, Joji; Sembill, Jochen; Sprügel, Maximilian; Hagen, Manuel; Knappe, Ruben U.; Endres, Matthias; Haeusler, Karl Georg; Sobesky, Jan; Schurig, Johannes; Zweynert, Sarah; Bauer, Miriam; et al. (Stroke, 2019)
Background and Purpose Given inconclusive studies, it is debated whether clinical and imaging characteristics, as well as functional outcome, differ among patients with intracerebral hemorrhage (ICH) related to vitamin K antagonists (VKA) versus non-vitamin K antagonist (NOAC)-related ICH. Notably, clinical characteristics according to different NOAC agents and dosages are not established.
CRIS-Team WoS Importer:2019-06-18

Characteristics of people with epilepsy in three Eastern African countries - a pooled analysis - Stelzle, Dominik; Kaducu, Joyce; Schmidt, Veronika; Welte, Tamara; Ngowi, Bernard J.; Matuja, William; Escheu, Gabrielle; Hauke, Peter; Richter, Vivien; Ovuga, Emilio; Pfausler, Bettina; Schmutzhard, Erich; et al. (BMC Neurology, 2022)
Background Epilepsy is one of the most common neurological disorders worldwide. Yet, its treatment gap is large in some areas and especially in sub-Saharan Africa data on clinical, radiological and semiological characteristics, as well as on treatment of persons with epilepsy (PWE) are still scarce. Methods We pooled data from four cross-sectional studies on epilepsy in eastern Africa. Two studies from Malawi and Uganda were community-based; two studies in Tanzania (urban Dar es Salaam and rural Haydom) were hospital-based. Clinical characteristics of PWE were assessed by the same questionnaire. Additionally, data on treatment were collected and computed tomography (CT) scans were performed. Results Overall, 1179 PWE were included in our analysis (581 (49.3%) female, median age 22 years (IQR 15-32 years)). Up to 25% of the patients had focal onset seizures. Those showed a higher rate of remarkable CT scan findings, with especially post-ischaemic and neurocysticercosis-associated lesions, compared to PWE with generalized onset seizures (35.1% vs. 20%). The majority of the patients experienced tonic-clonic seizures (70-85%). Only 67-78% of PWE received anti-seizure medication (ASM) treatment in the community-based studies, mostly monotherapy with phenobarbital, phenytoin or carbamazepine. Yet, underdosage was frequent and a large proportion of PWE received alternative non-ASM treatment consisting of herbal treatment (up to 83%) and/or scarification (up to 20%). Conclusions Epilepsy is common in sub-Saharan Africa, often caused by neurocysticercosis or ischaemic strokes. PWE suffer from high seizure rates and subsequent injuries, as well as from socio-economic consequences due to insufficient ASM treatment. This pooled analysis illustrates the need for structural programmes for adequate identification, education, assessment and treatment of PWE in sub-Saharan Africa.
CRIS-Team WoS Importer:2022-09-09

Characterization of gait variability in multiple system atrophy and Parkinson's disease - Sidoroff, Victoria; Raccagni, Cecilia; Kaindlstorfer, Christine; Eschlboeck, Sabine; Fanciulli, Alessandra; Granata, Roberta; Eskofier, Björn; Seppi, Klaus; Poewe, Werner; Willeit, Johann; Kiechl, Stefan; Mahlknecht, Philipp; et al. (Journal of Neurology, 2020)
Background Gait impairment is a pivotal feature of parkinsonian syndromes and increased gait variability is associated with postural instability and a higher risk of falls. Objectives We compared gait variability at different walking velocities between and within groups of patients with Parkinson-variant multiple system atrophy, idiopathic Parkinson's disease, and a control group of older adults. Methods Gait metrics were recorded in 11 multiple system atrophy, 12 Parkinson's disease patients, and 18 controls using sensor-based gait analysis. Gait variability was analyzed for stride, swing and stance time, stride length and gait velocity. Values were compared between and within the groups at self-paced comfortable, fast and slow walking speed. Results Multiple system atrophy patients displayed higher gait variability except for stride time at all velocities compared with controls, while Parkinson's patients did not. Compared with Parkinson's disease, multiple system atrophy patients displayed higher variability of swing time, stride length and gait velocity at comfortable speed and at slow speed for swing and stance time, stride length and gait velocity (all P < 0.05). Stride time variability was significantly higher in slow compared to comfortable walking in patients with multiple system atrophy (P = 0.014). Variability parameters significantly correlated with the postural instability/gait difficulty subscore in both disease groups. Conversely, significant correlations between variability parameters and MDS-UPDRS III score was observed only for multiple system atrophy patients. Conclusion This analysis suggests that gait variability parameters reflect the major axial impairment and postural instability displayed by multiple system atrophy patients compared with Parkinson's disease patients and controls.
CRIS-Team WoS Importer:2021-01-22

Chorea and the effectiveness of steroids in a patient with the syndrome of transient headache with neurologic deficits and cerebrospinal fluid lymphocytosis: A case report - Zhao, Lu; Wang, Ruihao; Fang, Hui; Song, Bo; Liang, Dongyi; Xu, Yuming (Journal of Pain Research, 2019)
Background: The clinical manifestations of the transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL) syndrome are variable, and involuntary movements have not been reported. The etiology and treatment of the syndrome are not entirely clarified. Case: A 25-year-old female presented with recurrent transient headache, involuntary movements (left upper extremity chorea) and paralysis. Lumbar punctures showed intracranial hypertension and cerebrospinal fluid pleocytosis. Symptoms and intracranial hypertension were relieved after administration of steroids. Discussion/conclusion: Chorea may also present in the HaNDL syndrome. Steroids might relieve the symptoms of the HaNDL syndrome, which indicates the possible treatment strategy for HaNDL and supports the infectious or postinfectious autoimmune etiology hypothesis.
CRIS-Team Scopus Importer:2019-08-06
Keywords: Intracranial hypertension; Involuntary movement; Steroids; Syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL)

Chronic Kidney Disease and Clinical Outcomes in Patients with Intracerebral Hemorrhage - Beuscher, Vanessa D.; Sprügel, Maximilian; Gerner, Stefan; Sembill, Jochen; Madzar, Dominik; Reindl, Caroline; Lücking, Hannes; Lang, Stefan; Kuramatsu, Joji; Huttner, Hagen; Hölter, Philip (Journal of Stroke and Cerebrovascular Diseases, 2020)
Background and Purpose: The influence of chronic kidney disease (CKD) on functional outcome in intracerebral hemorrhage (ICH) is scarcely investigated and reported findings are conflicting mostly because of nonaccounting for imbalances. Aim of the present study was to determine the impact of CKD on functional long-term outcome in ICH-patients. Methods: In this observational cohort study of spontaneous ICH-patients admitted to our Department of Neurology between 2006 and 2015 we investigated retrospectively as primary outcome the dichotomized functional status (modified-Rankin-Scale = 0-3-versus-4-6) at 12 months according to renal function (CKD versus non-CKD), including categorial estimates of the glomerular filtration rate subanalyses. Confounding was addressed by propensity-score(ps)-matching and adjusted multivariable regression analyses. Results: We identified 1076 eligible ICH-patients, of which 131 (12.2%) suffered from CKD on hospital admission. Confounders associated with CKD consisted of hypertension (P = .023), Diabetes mellitus (P = .001), prior ischemic stroke and/or transitory ischemic attack (TIA) (P = .021), congestive heart failure (P < .01), impaired liver function (P < .01), antiplatelet therapy (P = .01), poorer premorbid functional status (P < .01), and deep ICH-location (P = .006). After balancing for confounding, patients with CKD showed a significantly decreased rate of favorable functional outcome at 12 months (CKD:29 of 111(26.1%)-versus-non-CKD:78 of 206 (37.9%); P = .035). Subanalyses showed that stages of CKD were evenly associated with mortality at 12 months (GFR category G3a, OR:2.811; CI (1.130-6.994); P = .026; GFR category G3b, OR:1.874; CI (.694-5.058); P = .215; GFR category G4, OR:10.316; CI (1.976-53.856); P = .006; GFR category G5, OR:8.989; CI (1.900-42.518); P = .006). Conclusions: As compared to ICH-patients without CKD, those with CKD show increased rates of mortality and worse functional outcomes even after statistical correction for imbalanced baseline characteritsics. This finding is presumably linked to comorbidity and warrants further investigation in prospective studies.
CRIS-Team Scopus Importer:2020-04-28
Keywords: Chronic kidney disease; critical care; intracerebral hemorrhage; mortality; outcome

Chronic peripheral inflammation: A possible contributor to neurodegenerative diseases - Süß, Patrick; Lana, Addison J.; Schlachetzki, Johannes C.M. (Neural Regeneration Research, 2021)
The contribution of chronic peripheral inflammation to the pathogenesis of neurodegenerative diseases is an outstanding question. Sustained activation of the peripheral innate and adaptive immune systems occurs in the context of a broad array of disorders ranging from chronic infectious diseases to autoimmune and metabolic diseases. In addition, progressive systemic inflammation is increasingly recognized during aging. Peripheral immune cells could potentially modulate the cellular brain environment via the secretion of soluble molecules. There is an ongoing debate whether peripheral immune cells have the potential to migrate into the brain under certain permissive circumstances. In this perspective, we discuss the possible contribution of chronic peripheral inflammation to the pathogenesis of age-related neurodegenerative diseases with a focus on microglia, the resident immune cells of the brain parenchyma.
CRIS-Team Scopus Importer:2021-02-12
Keywords: aging; Alzheimer's disease; inflammation; innate immune system; microglia; neurodegeneration; Parkinson's disease

Chronic Peripheral Inflammation Causes a Region-Specific Myeloid Response in the Central Nervous System - Süß, Patrick; Hoffmann, Alana; Rothe, Tobias; Ouyang, Zhengyu; Baum, Wolfgang; Staszewski, Ori; Schett, Georg; Prinz, Marco; Krönke, Gerhard; Glass, Christopher K.; Winkler, Jürgen; Schlachetzki, Johannes (Cell Reports, 2020)
Systemic immune dysregulation contributes to the development of neuropsychiatric and neurodegenerative diseases. The precise effect of chronic peripheral immune stimulation on myeloid cells across anatomical brain regions is unclear. Here, we demonstrate brain-region-specific differences in myeloid responses induced by chronic peripheral inflammation. This shift in the myeloid compartment is associated with the appearance of an inflammatory myeloid subpopulation in the cortex, striatum, and thalamus accompanied by regional transcriptomic fingerprints that include induction of chemokines, complement factors, and endothelial adhesion molecules. In contrast, myeloid immune responses within the hippocampus and cerebellum are subtle or absent. Treatment with the anti-tumor necrosis factor α (anti-TNF-α) antibody infliximab ablates the region-specific inflammatory response. A region-specific myeloid cell response to chronic peripheral inflammation is observed in postmortem brains from individuals with rheumatoid arthritis. Our data suggest that chronic peripheral inflammation has heterogeneous effects on the brain, as evidenced by the spectrum of myeloid cell responses observed across brain regions.
CRIS-Team Scopus Importer:2020-03-31
Keywords: blood-brain barrier; brain regions; chronic peripheral inflammation; CNS myeloid cells; human rheumatoid arthritis; microglia

Chronic valproate or levetiracetam treatment does not influence cytokine levels in humans - Guenther, Sabina; Bauer, Sebastian; Hagge, Mareike; Knake, Susanne; Olmes, David G.; Tackenberg, Bjoern; Rosenow, Felix; Hamer, Hajo M. (Seizure-European Journal of Epilepsy, 2014)
There is growing evidence that complex interactions between seizures and the immune system shape the course of epilepsy. However, systematic analyses of the effects of antiepileptic drugs (AED) on the immune system in humans are rare. We performed a prospective study on the influence of the widely used AED valproate and levetiracetam on interictal immunological parameters.36 patients were prospectively included. 15 were started on valproate (5 female (33%), age 54±27 years, 12 (80%) on monotherapy), 21 on levetiracetam (10 female (48%), age 45±19 years, 17 (81%) on monotherapy). Before treatment and after 3 months, we performed a differential blood count and analyzed the distribution of CD3(+)CD4(+)-, CD3(+)CD8(+)- and CD4(+)CD25(+)-leukocyte subsets using flow cytometry. In addition, we determined the concentrations of IL-1?, IL-6, TNF-? and MCP-1 in the peripheral blood using ELISAs.Valproate intake resulted in a significant decrease of the total white blood count (6.96±1.23/nl vs. 6.13±1.57/nl, p=0.026) and of absolute count and percentage of neutrophils (4.60±1.05/nl vs. 3.69±1.30/nl, p=0.01; 65.4±7.9% vs. 59.5±11.5%, p=0.01, respectively). The percentage of CD3(+)CD4(+)-lymphocytes dropped significantly (50.4±10.9% vs. 45.3±12.3%, p=0.002). Levetiracetam treatment resulted in a decrease of the percentage of CD4(+)CD25(+)-lymphocytes (26.1±8.0% vs. 21.5±9.2%, p=0.01) but did not significantly alter absolute counts. Neither valproate nor levetiracetam were associated with significant changes in cytokines.Valproate intake results in profound changes of white blood cell count and subset distribution. Cytokine levels were not influenced by valproate or levetiracetam.
EVALuna2:22288

Classification of paroxysmal events and the four-dimensional epilepsy classification system - Luders, Hans; Vaca, Guadalupe Fernandez-Baca; Akamatsu, Naoki; Amina, Shahram; Arzimanoglou, Alexis; Baumgartner, Christoph; Benbadis, Selim R.; Bleasel, Andrew; Bermeo-Ovalle, Adriana; Bozorgi, Alireza; Carreno, Mar; Devereaux, Michael; et al. (Epileptic Disorders, 2019)
This educational review describes the classification of paroxysmal events and a four-dimensional epilepsy classification system. Paroxysmal events are classified as epileptic and non-epileptic paroxysmal events. Non-epileptic events are, in turn, classified as psychogenic and organic paroxysmal events. The following four dimensions are used to classify epileptic paroxysmal events: ictal semiology, the epileptogenic zone, etiology, and comorbidities. Efforts are made to keep these four dimensions as independent as possible. The review also includes 12 educational vignettes and three more detailed case reports classified using the 2017 classification of the ILAE and the four-dimensional epilepsy classification. In addition, a case is described which is classified using the four-dimensional epilepsy classification with different degrees of precision by an emergency department physician, a neurologist, and an epileptologist. [Published with video sequences on www.epilepticdisorders.com].
EVALuna2:204546

Classification of primary cerebral lymphoma and glioblastoma featuring dynamic susceptibility contrast and apparent diffusion coefficient - Eisenhut, Felix; Schmidt, Manuel; Putz, Florian; Lettmaier, Sebastian; Fröhlich, Kilian; Arinrad, Soheil; Coras, Roland; Lücking, Hannes; Lang, Stefan; Fietkau, Rainer; Dörfler, Arnd (Brain Sciences, 2020)
This study aimed to differentiate primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) via multimodal MRI featuring radiomic analysis. MRI data sets of patients with histological proven PCNSL and GBM were analyzed retrospectively. Diffusion-weighted imaging (DWI) and dynamic susceptibility contrast (DSC) perfusion imaging were evaluated to differentiate contrast enhancing intracerebral lesions. Selective (contrast enhanced tumor area with the highest mean cerebral blood volume (CBV) value) and unselective (contouring whole contrast enhanced lesion) Apparent diffusion coefficient (ADC) measurement was performed. By multivariate logistic regression, a multiparametric model was compiled and tested for its diagnostic strength. A total of 74 patients were included in our study. Selective and unselective mean and maximum ADC values, mean and maximum CBV and ratioCBV as quotient of tumor CBV and CBV in contralateral healthy white matter were significantly larger in patients with GBM than PCNSL; minimum CBV was significantly lower in GBM than in PCNSL. The highest AUC for discrimination of PCNSL and GBM was obtained for selective mean and maximum ADC, mean and maximum CBV and ratioCBV. By integrating these five in a multiparametric model 100% of the patients were classified correctly. The combination of perfusion imaging (CBV) and tumor hot-spot selective ADC measurement yields reliable radiological discrimination of PCNSL from GBM with highest accuracy and is readily available in clinical routine.
CRIS-Team Scopus Importer:2020-12-04
Keywords: ADC; DSC; Glioblastoma; MRI; Multimodal; Primary central nervous system lymphoma

Clinical and genetic characterization of SPG11: Hereditary Spastic Paraplegia with thin corpus callosum - Winner, Beate; Winkler, Jürgen; Uyanik, Goekhan; Cirak, Sebahattin; Hehr, Ute; et al. (Neuromuscular Disorders, 2006)

Clinical and genetic features of amyotrophic lateral sclerosis patients with C9orf72 mutations - Wiesenfarth, Maximilian; Gunther, Kornelia; Muller, Kathrin; Witzel, Simon; Weiland, Ulrike; Mayer, Kristina; Herrmann, Christine; Brenner, David; Schuster, Joachim; Freischmidt, Axel; Lule, Dorothee; Meyer, Thomas; et al. (Brain Communications, 2023)
An expansion of the GGGGCC hexanucleotide in the non-coding region of C9orf72 represents the most common cause of familial amyotrophic lateral sclerosis. The objective was to describe and analyse the clinical and genetic features of amyotrophic lateral sclerosis patients with C9orf72 mutations in a large population. Between November 2011 and December 2020, clinical and genetic characteristics of n = 248 patients with amyotrophic lateral sclerosis carrying C9orf72 mutations were collected from the clinical and scientific network of German motoneuron disease centres. Clinical parameters included age of onset, diagnostic delay, family history, neuropsychological examination, progression rate, phosphorylated neurofilament heavy chain levels in CSF and survival. The number of repeats was correlated with the clinical phenotype. The clinical phenotype was compared to n = 84 patients with SOD1 mutations and n = 2178 sporadic patients without any known disease-related mutations. Patients with C9orf72 featured an almost balanced sex ratio with 48.4% (n = 120) women and 51.6% (n = 128) men. The rate of 33.9% patients (n = 63) with bulbar onset was significantly higher compared to sporadic (23.4%, P = 0.002) and SOD1 patients (3.1%, P < 0.001). Of note, 56.3% (n = 138) of C9orf72, but only 16.1% of SOD1 patients reported a negative family history (P < 0.001). The GGGGCC hexanucleotide repeat length did not influence the clinical phenotypes. Age of onset (58.0, interquartile range 52.0-63.8) was later compared to SOD1 (50.0, interquartile range 41.0-58.0; P < 0.001), but earlier compared to sporadic patients (61.0, interquartile range 52.0-69.0; P = 0.01). Median survival was shorter (38.0 months) compared to SOD1 (198.0 months, hazard ratio 1.97, 95% confidence interval 1.34-2.88; P < 0.001) and sporadic patients (76.0 months, hazard ratio 2.34, 95% confidence interval 1.64-3.34; P < 0.001). Phosphorylated neurofilament heavy chain levels in CSF (2880, interquartile range 1632-4638pg/ml) were higher compared to sporadic patients (1382, interquartile range 458-2839pg/ml; P < 0.001). In neuropsychological screening, C9orf72 patients displayed abnormal results in memory, verbal fluency and executive functions, showing generally worse performances compared to SOD1 and sporadic patients and a higher share with suspected frontotemporal dementia. In summary, clinical features of patients with C9orf72 mutations differ significantly from SOD1 and sporadic patients. Specifically, they feature a more frequent bulbar onset, a higher share of female patients and shorter survival. Interestingly, we found a high proportion of patients with negative family history and no evidence of a relationship between repeat lengths and disease severity.
CRIS-Team Scopus Importer:2023-05-12
Keywords: motor neuron disease

Clinical and Imaging Characteristics in Noac-Related Intracerebral Hemorrhage. - Gerner, Stefan; Kuramatsu, Joji; Schwab, Stefan; Huttner, Hagen (STROKE, 2019)
CRIS-Team WoS Importer:2019-08-23

Clinical and patient-reported outcomes and neurofilament response during tofersen treatment in SOD1-related ALS—A multicenter observational study over 18 months - Meyer, Thomas; Schumann, Peggy; Weydt, Patrick; Petri, Susanne; Weishaupt, Jochen H.; Weyen, Ute; Koch, Jan C.; Günther, René; Regensburger, Martin; Boentert, Matthias; Wiesenfarth, Maximilian; Koc, Yasemin; et al. (Muscle & Nerve, 2024)
Introduction/Aims: In amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (SOD1-ALS), tofersen received accelerated approval in the United States and is available via expanded access programs (EAP) outside the United States. This multicenter study investigates clinical and patient-reported outcomes (PRO) and serum neurofilament light chain (sNfL) during tofersen treatment in an EAP in Germany. Methods: Sixteen SOD1-ALS patients receiving tofersen for at least 6 months were analyzed. The ALS progression rate (ALS-PR), as measured by the monthly change of the ALS functional rating scale—revised (ALSFRS-R), slow vital capacity (SVC), and sNfL were investigated. PRO included the Measure Yourself Medical Outcome Profile (MYMOP2), Treatment Satisfaction Questionnaire for Medication (TSQM-9), and Net Promoter Score (NPS). Results: Mean tofersen treatment was 11 months (6–18 months). ALS-PR showed a mean change of −0.2 (range 0 to −1.1) and relative reduction by 25%. Seven patients demonstrated increased ALSFRS-R. SVC was stable (mean 88%, range −15% to +28%). sNfL decreased in all patients except one heterozygous D91A-SOD1 mutation carrier (mean change of sNfL −58%, range −91 to +27%, p <.01). MYMOP2 indicated improved symptom severity (n = 10) or yet perception of partial response (n = 6). TSQM-9 showed high global treatment satisfaction (mean 83, SD 16) although the convenience of drug administration was modest (mean 50, SD 27). NPS revealed a very high recommendation rate for tofersen (NPS +80). Discussion: Data from this EAP supported the clinical and sNfL response to tofersen in SOD1-ALS. PRO suggested a favorable patient perception of tofersen treatment in clinical practice.
CRIS-Team Scopus Importer:2024-06-28
Keywords: amyotrophic lateral sclerosis (ALS); clinical course; neurofilament light chain (NfL); patient-reported outcomes; tofersen

Clinical and radiological outcome after mechanical thrombectomy in acute ischemic stroke: What matters? - Kaschka, Iris; Kloska, Stephan; Struffert, Tobias; Engelhorn, Tobias; Gölitz, Philipp; Kurka, Natalia; Köhrmann, Martin; Schwab, Stefan; Dörfler, Arnd (Neuroradiology Journal, 2016)
Recent studies have shown the efficacy of mechanical thrombectomy in acute ischemic stroke. We sought to identify prognostic parameters for clinical and radiological outcome after mechanical thrombectomy.In 34 patients (age 72 ± 13 years, 64.7% women) with acute occlusion of the distal ICA and/or M1 segment who were treated with mechanical thrombectomy, the Spearman correlation was performed to assess potential prognostic outcome parameters (age, NIHSS, ASPECT, thrombus length (TL), clot burden score (CBS), relative filling time delay (rFTD), time to recanalization (TTR) and TICI score). The modified Rankin scale (mRS) and the Alberta Stroke Program Early CT (ASPECT) score were used for clinical and radiological outcome, respectively. Receiver operating characteristic (ROC) analysis was performed to assess parameters predicting favorable clinical (?mRS <= 2) and radiological outcome (?ASPECT <= 2).Variables associated with favorable clinical outcome included NIHSS, TL, TTR and TICI score (p <= 0.01) with NIHSS <= 15 (p = 0.001, area under the curve (AUC) 0.87), TL <= 2 cm (p = 0.017, AUC 0.75), TTR <= 231 min (p = 0.001 AUC 0.88) and TICI >= 2b (p = 0.050, AUC 0.70). Shorter TTR and higher TICI scores were associated with favorable radiological outcome (p < 0.001) with TTR <= 224 min (p = 0.023, AUC 0.77) and TICI >= 2b (p = 0.000, AUC 0.86).Fast and complete recanalization is essential to achieve a favorable radiological and functional outcome after mechanical thrombectomy in acute ischemic stroke. Age, CBS and collateral supply play a subordinate role.
EVALuna2:22544

Clinical benefit of MAO-B and COMT inhibition in Parkinson’s disease: practical considerations - Regensburger, Martin; Ip, Chi Wang; Kohl, Zacharias; Schrader, Christoph; Urban, Peter P.; Kassubek, Jan; Jost, Wolfgang H. (Journal of Neural Transmission, 2023)
Inhibitors of monoamine oxidase B (MAO-B) and catechol-O-methyltransferase (COMT) are major strategies to reduce levodopa degradation and thus to increase and prolong its effect in striatal dopaminergic neurotransmission in Parkinson’s disease patients. While selegiline/rasagiline and tolcapone/entacapone have been available on the market for more than one decade, safinamide and opicapone have been approved in 2015 and 2016, respectively. Meanwhile, comprehensive data from several post-authorization studies have described the use and specific characteristics of the individual substances in clinical practice under real-life conditions. Here, we summarize current knowledge on both medication classes, with a focus on the added clinical value in Parkinson’s disease. Furthermore, we outline practical considerations in the treatment of motor fluctuations and provide an outlook on ongoing studies with MAO-B and COMT inhibitors.
CRIS-Team Scopus Importer:2023-03-31
Keywords: COMT inhibitors; MAO-B inhibitors; Motor fluctuations; Parkinson’s disease

Clinical characterization of common pathogenic variants of SOD1-ALS in Germany - Wiesenfarth, Maximilian; Forouhideh-Wiesenfarth, Yalda; Elmas, Zeynep; Parlak, Özlem; Weiland, Ulrike; Herrmann, Christine; Schuster, Joachim; Freischmidt, Axel; Müller, Kathrin; Siebert, Reiner; Günther, Kornelia; Fröhlich, Elke; et al. (Journal of Neurology, 2024)
Pathogenic variants in the Cu/Zn superoxide dismutase (SOD1) gene can be detected in approximately 2% of sporadic and 11% of familial amyotrophic lateral sclerosis (ALS) patients in Europe. We analyzed the clinical phenotypes of 83 SOD1-ALS patients focusing on patients carrying the most frequent (likely) pathogenic variants (R116G, D91A, L145F) in Germany. Moreover, we describe the effect of tofersen treatment on ten patients carrying these variants. R116G patients showed the most aggressive course of disease with a median survival of 22.0 months compared to 198.0 months in D91A and 87.0 months in L145F patients (HR 7.71, 95% CI 2.89–20.58 vs. D91A; p < 0.001 and HR 4.25, 95% CI 1.55–11.67 vs. L145F; p = 0.02). Moreover, R116G patients had the fastest median ALSFRS-R progression rate with 0.12 (IQR 0.07–0.20) points lost per month. Median diagnostic delay was 10.0 months (IQR 5.5–11.5) and therefore shorter compared to 57.5 months (IQR 14.0–83.0) in D91A (p < 0.001) and 21.5 months (IQR 5.8–38.8) in L145F (p = 0.21) carriers. As opposed to D91A carriers (50.0%), 96.2% of R116G (p < 0.001) and 100.0% of L145F (p = 0.04) patients reported a positive family history. During tofersen treatment, all patients showed a reduction of neurofilament light chain (NfL) serum levels, independent of the SOD1 variant. Patients with SOD1-ALS carrying R116G, D91A, or L145F variants show commonalities, but also differences in their clinical phenotype, including a faster progression rate with shorter survival in R116G, and a comparatively benign disease course in D91A carriers.
CRIS-Team Scopus Importer:2024-08-23
Keywords: Amyotrophic lateral sclerosis; Clinical phenotype; Motor neuron disease; SOD1; Tofersen

Clinical features, pathogenesis, and treatment of myasthenia gravis: a supplement to the Guidelines of the German Neurological Society - Melzer, Nico; Ruck, Tobias; Fuhr, Peter; Gold, Ralf; Hohlfeld, Reinhard; Marx, Alexander; Melms, Arthur; Tackenberg, Bjoern; Schalke, Berthold; Schneider-Gold, Christiane; Zimprich, Fritz; Meuth, Sven G.; et al. (Journal of Neurology, 2016)
Myasthenia gravis (MG) is an autoimmune antibody-mediated disorder of neuromuscular synaptic transmission. The clinical hallmark of MG consists of fluctuating fatigability and weakness affecting ocular, bulbar and (proximal) limb skeletal muscle groups. MG may either occur as an autoimmune disease with distinct immunogenetic characteristics or as a paraneoplastic syndrome associated with tumors of the thymus. Impairment of central thymic and peripheral self-tolerance mechanisms in both cases is thought to favor an autoimmune CD4(+) T cell-mediated B cell activation and synthesis of pathogenic high-affinity autoantibodies of either the IgG1 and 3 or IgG4 subclass. These autoantibodies bind to the nicotinic acetylcholine receptor (AchR) itself, or muscle-specific tyrosine-kinase (MuSK), lipoprotein receptor-related protein 4 (LRP4) and agrin involved in clustering of AchRs within the postsynaptic membrane and structural maintenance of the neuromuscular synapse. This results in disturbance of neuromuscular transmission and thus clinical manifestation of the disease. Emphasizing evidence from clinical trials, we provide an updated overview on immunopathogenesis, and derived current and future treatment strategies for MG divided into: (a) symptomatic treatments facilitating neuromuscular transmission, (b) antibody-depleting treatments, and
EVALuna2:22518

Clinical/perfusion CT CBV mismatch as prognostic factor in intraarterial thrombectomy in acute anterior circulation stroke - Saake, Marc; Breuer, Lorenz; Gölitz, Philipp; Köhrmann, Martin; Schwab, Stefan; Dörfler, Arnd; Kloska, Stephan (Clinical Neurology and Neurosurgery, 2014)
Contradictory results were reported for the outcome after endovascular recanalization (ERT) in acute anterior circulation ischemic stroke. We assessed whether a clinical/perfusion CT cerebral blood volume (CBV) mismatch concept (CPM) can identify patients who will benefit from reperfusion therapy.Imaging and clinical data of 58 consecutive ERT cases with acute anterior circulation stroke (ICA, M1, proximal M2) undergoing intraarterial thrombectomy within 4.5h after symptom onset were analyzed retrospectively. CPM was defined as NIHSS>=8 and PCT CBV ASPECTS>=7. Minor CBV lesion was defined as PCT CBV ASPECTS>=7.All baseline characteristics other than blood glucose did not differ between the paired groups. Revascularization was achieved in 87.9% of all patients without significant difference between the paired groups. Favorable clinical outcome after 3 months (mRS<=2) resulted in 29.3% of all patients, in contrast to 47.4% of the CPM positive and 52.2% of the minor CBV lesion groups.CPM can identify patients who will benefit from reperfusion therapy in acute anterior circulation ischemic stroke.
EVALuna2:14386

Clinical relevance of source location in frontal lobe epilepsy and prediction of postoperative long-term outcome - Mu, Jie; Rampp, Stefan; Carrette, Evelien; Roessler, Karl; Sommer, Bjoern; Schmitt, Friedhelm Carl; De Tiege, Xavier; Hamer, Hajo; Boon, Paul; Pauli, Elisabeth; Blümcke, Ingmar; Zhou, Dong; et al. (Seizure-European Journal of Epilepsy, 2014)
To evaluate the value of magnetoencephalography (MEG) source localization in localization of epileptic activities and predicting surgical outcome in frontal lobe epilepsies (FLE).Forty-six patients with presurgical MEG evaluation and intractable FLE surgery (28 male patients) were analyzed retrospectively with a mean follow-up of 5 years. Dipole analysis was performed for MEG source imaging (MSI). The localization of dipole clusters in relation to the dominant hemisphere, lesions, resection cavity and functional cortex were analyzed. The predictive value of MSI in respect to clinical outcome with long-term postoperative follow up was evaluated.Interictal focal epileptic activities were found in 82.6% (38/46) patients with monofocal activity 81.6% (31/38) and multifocal activities 18.4% (7/38). Seizure free rate was 47.9% at the mean follow-up of 5.0 ± 4.0 years (median 11.5, range 2-57). Seizure recurrence mainly occurred in the first 1 year after surgery. In the monofocal epileptic activity group, 58.1% (18/31) of the patients were seizure free, predicitng postoperative seizure freedom better than multifocal localization 0% (0/7) (p=0.028). Dipole clusters were completely resected in 70.9% of monofocal activity patients, which had higher seizure free rates compared to partial resection (p=0.002). In patients with surgery in the dominant hemisphere, seizure control was less likely (p=0.006).MSI contributes to the clinical prediction of postoperative outcome in FLE patients. MSI may non-invasively disclose early epileptogenic lesions, pointing to a resectable lesion, and it then facilitates shortcut route of presurgical evaluation.
EVALuna2:7256

Clinical Relevance of Standardized Mobile Gait Tests. Reliability Analysis Between Gait Recordings at Hospital and Home in Parkinson's Disease: A Pilot Study - Gaßner, Heiko; Sanders, Philipp; Dietrich, Alisa; Marxreiter, Franz; Eskofier, Björn; Winkler, Jürgen; Klucken, Jochen (Journal of Parkinson's Disease, 2020)
BACKGROUND: Gait impairments in Parkinson's disease (PD) are quantified using inertial sensors under standardized test settings in the hospital. Recent studies focused on the assessment of free-living gait in PD. However, the clinical relevance of standardized gait tests recorded at the patient's home is unclear. OBJECTIVE: To evaluate the reliability of supervised, standardized sensor-based gait outcomes at home compared to the hospital. METHODS: Patients with PD (n = 20) were rated by a trained investigator using the Unified Parkinson Disease Rating Scale (UPDRS-III). Gait tests included a standardized 4×10 m walk test and the Timed Up and Go Test (TUG). Tests were performed in the hospital (HOSPITAL) and at patients' home (HOME), and controlled for investigator, time of the day, and medication. Statistics included reliability analysis using Intra-Class correlations and Bland-Altman plots. RESULTS: UPDRS-III and TUG were comparable between HOSPITAL and HOME. PD patients' gait at HOME was slower (gait velocity Δ= -0.07±0.11 m/s, -6.1%), strides were shorter (stride length Δ= -9.2±9.4 cm; -7.3%), and shuffling of gait was more present (maximum toe-clearance Δ= -0.7±2.5 cm; -8.8%). Particularly, narrow walkways (<85 cm) resulted in a significant reduction of gait velocity at home. Reliability analysis (HOSPITAL vs. HOME) revealed excellent ICC coefficients for UPDRS-III (0.950, p < 0.000) and gait parameters (e.g., stride length: 0.898, p < 0.000; gait velocity: 0.914, p < 0.000; stance time: 0.922, p < 0.000; stride time: 0.907, p < 0.000). CONCLUSION: This pilot study underlined the clinical relevance of gait parameters by showing excellent reliability for supervised, standardized gait tests at HOSPITAL and HOME, even though gait parameters were different between test conditions.
CRIS-Team Scopus Importer:2020-11-13
Keywords: gait analysis; home monitoring; Parkinson’s disease; telemedicine; wearable sensors

Clinical/scientific notes - Möller, Sebastian; Hilz, Max-Josef; Blinzler, C.; Köhn, Julia; Dörfler, Arnd; Schwab, Stefan; Köhrmann, Martin (Neurology, 2012)
CRIS-Team Scopus Importer:2022-08-05

Clinical, serological and genetic predictors of response to immunotherapy in anti-IgLON5 disease - Grueter, Thomas; Moellers, Franziska E.; Tietz, Anja; Dargvainiene, Justina; Melzer, Nico; Heidbreder, Anna; Strippel, Christine; Kraft, Andrea; Hoeftberger, Romana; Schoeberl, Florian; Thaler, Franziska S.; Wickel, Jonathan; et al. (Brain, 2022)
In a large cohort of anti-IgLON5 disease patients, Gruter et al. reveal early inflammatory CSF changes, subacute relapses, and association of HLA-DRB1*10:01 with higher autoantibody titre, consistent with a primary autoimmune nature of the disease. Immunotherapy is effective if initiated early, prior to major neurodegeneration.
CRIS-Team WoS Importer:2023-01-06

Clinical Studies Targeting Stroke and Ischemic Insults - Lundbye, Justin; Lyden, Patrick D.; Polderman, Kees H.; Schwab, Stefan (Therapeutic Hypothermia and Temperature Management, 2017)
EVALuna2:33131

CLIPPERS with longitudinally extensive transverse myelitis: Role of T versus B cells - Olmes, David G.; Metz, Imke; Lee, De-Hyung; Rosenwald, Andreas; Dörfler, Arnd; Brueck, Wolfgang; Linker, Ralf (Journal of the Neurological Sciences, 2018)
EVALuna2:35521

Cocreating the Visualization of Digital Mobility Outcomes: Delphi-Type Process With Patients - Lumsdon, Jack; Wilson, Cameron; Alcock, Lisa; Becker, Clemens; Benvenuti, Francesco; Bonci, Tecla; van den Brande, Koen; Brittain, Gavin; Brown, Philip; Buckley, Ellen; Caruso, Marco; Caulfield, Brian; et al. (JMIR Formative Research, 2025)
Background: Recent technological advances in wearable devices offer new potential for measuring mobility in real-world contexts. Mobilise-D has validated digital mobility outcomes to provide novel outcomes and end points in clinical research of 4 different long-term health conditions (Parkinson disease, multiple sclerosis, chronic obstructive pulmonary disease, and proximal femoral fracture). These outcomes also provide unique information that is important to patients; however, there is limited literature that explores the optimal methods to achieve this, such as the best way to visualize patients’ data. Objective: This study aimed to identify meaningful outcomes for each condition and how to best visualize them from the perspective of end users. Methods: Using a Delphi-type protocol with patients as subject matter experts, we gathered iterative feedback on the cocreation of visualizations through 3 rounds of questionnaires. An open-ended questionnaire was used in round 1 to understand what aspects of mobility were most influenced by their health condition. These responses were mapped onto relevant digital mobility outcomes and walking experiences and then prioritized for visualization. Using patient responses, we worked alongside researchers, clinicians, and a patient advisory group to develop visualizations that depicted a week of mobility data. During rounds 2 and 3, participants rated usefulness and ease of understanding on a 5-point Likert scale and provided unstructured feedback in comment boxes for each visualization. Visualizations were refined using the feedback from round 2 before receiving further feedback in round 3. Results: Participation varied across rounds 1 to 3 (n=48, n=79, and n=78, respectively). Round 1 identified important outcomes and contexts for each health condition, such as walking speed and stride length for people with Parkinson disease or multiple sclerosis and number of steps for people with chronic obstructive pulmonary disease or proximal femoral fracture. The consensus was not reached for any visualization reviewed in round 2 or 3. Feedback was generally positive, and some participants reported that they were able to understand the visualization and interpret what the visualization represented. Conclusions: Through the feedback provided and existing data visualization principles, we developed recommendations for future visualizations of mobility- and health-related data. Visualizations should be readable by ensuring that large and clear fonts are used and should be friendly for people with vision impairments, such as color blindness. Patients have a strong understanding of their own condition and its variability; hence, adding additional factors into visualizations is recommended to better reflect the nuances of a condition. Ensuring that outcomes and visualizations are meaningful requires close collaboration with patients throughout the development process.
CRIS-Team Scopus Importer:2025-05-23
Keywords: cocreation; data visualization; digital mobility outcomes; mobility; wearable devices

Cognitive functions over the course of 1 year in multiple sclerosis patients treated with disease modifying therapies - Utz, Kathrin S.; Lee, De-Hyung; Laemmer, Alexandra; Waschbisch, Anne; Linker, Ralf; Schenk, Thomas (Therapeutic Advances in Neurological Disorders, 2016)
Disease-modifying therapies (DMTs) are applied to delay or prevent disease progression in multiple sclerosis (MS). While this has mostly been proven for physical symptoms, available studies regarding long-term effects of DMTs on cognitive functions are rare and sometimes inconsistent due to methodological shortcomings. Particularly in the case of fingolimod, comprehensive data on cognitive functions are not yet available. Therefore, we set out to reliably assess cognitive functions in patients with relapsing-remitting MS (RRMS) treated with DMTs over 1 year.Cognitive functions were assessed with eight tests at three timepoints: baseline, 6-month follow up and 12-month follow up. First, we investigated whether the stability of cognitive functions (i.e. not falling below the 5% cut-off in more than one test) over 1 year in RRMS patients (n = 41) corresponds to the stability in healthy individuals (n = 40) of a previous study. Second, we compared the percentage of declined and improved patients in the different tests. Third, we compared patients treated with fingolimod (n = 22) with patients treated with natalizumab (n = 11) with regard to cognitive stability. Fourth, based on the patient data, the Reliable Change Index was applied to compute cut-offs for reliable cognitive change.Approximately 75% of RRMS patients treated with DMTs remained stable over the course of 1 year. The Paced Auditory Serial Addition Test (PASAT) and the Spatial Recall Test (SPART), produced improvements in 12.5% and 30.6%, respectively, probably due to practice effects. Patients treated with fingolimod did not differ from patients treated with natalizumab with regard to cognitive stability.Cognitive functions remain relatively stable under DMT treatment over 1 year, irrespective of the type of medication. Furthermore, the tests PASAT and SPART should be interpreted cautiously in studies examining performance changes over time. The provided RCI norms may help clinicians to determine whether a difference in two measurements observed in a RRMS patient is reliable.
EVALuna2:22528

Cognitive impairment correlates with autonomic dysfunction in patients with a history of traumatic brain injury - Hilz, Max-Josef; de Rojas Leal, Carmen; Roy, Sankanika; Liu, Mao; Hoesl, Katharina M.; Winder, Klemens; Wang, Ruihao (2018)
EVALuna2:201954

Combination of defined catwalk gait parameters for predictive locomotion recovery in experimental spinal cord injury rat models - Timotius, Ivanna; Bieler, Lara; Couillard-Despres, Sebastien; Sandner, Beatrice; Garcia-Ovejero, Daniel; Labombarda, Florencia; Estrada, Veronica; Müller, Hans W.; Winkler, Jürgen; Klucken, Jochen; Eskofier, Björn; Weidner, Norbert; et al. (eNeuro, 2021)
In many preclinical spinal cord injury (SCI) studies, assessment of locomotion recovery is key to understanding the effectiveness of the experimental intervention. In such rat SCI studies, the most basic locomotor recovery scoring system is a subjective observation of animals freely roaming in an open field, the Basso Beattie Bresnahan (BBB) score. In comparison, CatWalk is an automated gait analysis system, providing further parameter specifications. Although together the CatWalk parameters encompass gait, studies consistently report single parameters, which differ in significance from other behavioral assessments. Therefore, we believe no single parameter produced by the CatWalk can represent the fully-coordinated motion of gait. Typically, other locomotor assessments, such as the BBB score, combine several locomotor characteristics into a representative score. For this reason, we ranked the most distinctive CatWalk parameters between uninjured and SC injured rats. Subsequently, we combined nine of the topmost parameters into an SCI gait index score based on linear discriminant analysis (LDA). The resulting combination was applied to assess gait recovery in SCI experiments comprising of three thoracic contusions, a thoracic dorsal hemisection, and a cervical dorsal column lesion model. For thoracic lesions, our unbiased machine learning model revealed gait differences in lesion type and severity. In some instances, our LDA was found to be more sensitive in differentiating recovery than the BBB score alone. We believe the newly developed gait parameter combination presented here should be used in CatWalk gait recovery work with preclinical thoracic rat SCI models.
CRIS-Team Scopus Importer:2021-03-19
Keywords: CatWalk; Gait parameter; Linear discriminant analysis; Locomotion recovery; Preclinical development; Spinal cord injury

Combined Accelerometer and EMG Analysis to Differentiate Essential Tremor from Parkinson’s Disease - Haji Ghassemi, Nooshin; Marxreiter, Franz; Pasluosta, Cristian Federico; Schlachetzki, Johannes; Schramm, A; Eskofier, Björn; Klucken, Jochen (38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society of the IEEE Engineering in Medicine and Biology Society EMBC'16, 2016)

Combined analysis of sensor data from hand and gait motor function improves automatic recognition of Parkinson's disease - Barth, Jens; Sünkel, Michael; Bergner, Katharina; Schickhuber, Gerald; Winkler, Jürgen; Klucken, Jochen; Eskofier, Björn (Engineering in Medicine and Biology Society (EMBC), 2012 Annual International Conference of the IEEE, 2012)
Objective and rater independent analysis of movement impairment is one of the most challenging tasks in medical engineering. Especially assessment of motor symptoms defines the clinical diagnosis in Parkinson's disease (PD). A sensor-based system to measure the movement of the upper and lower extremities would therefore complement the clinical evaluation of PD. In this study two different sensor-based systems were combined to assess movement of 18 PD patients and 17 healthy controls. First, hand motor function was evaluated using a sensor pen with integrated accelerometers and pressure sensors, and second, gait function was assessed using a sports shoe with attached inertial sensors (gyroscopes, accelerometers). Subjects performed standardized tests for both extremities. Features were calculated from sensor signals to differentiate between patients and controls. For the latter, pattern recognition methods were used and the performance of four classifiers was compared. In a first step classification was done for every single system and in a second step for combined features of both systems. Combination of both motor task assessments substantially improved classification rates to 97% using the AdaBoost classifier for the experiment patients vs. controls. The combination of two different analysis systems led to enhanced, more stable, objective, and rater independent recognition of motor impairment. The method can be used as a complementary diagnostic tool for movement disorders.

Comment on 2018 ESC/ESH Guidelines for the management of arterial hypertension - Haeusler, Karl Georg; Huttner, Hagen; Kuramatsu, Joji (European Heart Journal, 2019)
CRIS-Team Scopus Importer:2019-07-26

Community-level prevalence of epilepsy and of neurocysticercosis among people with epilepsy in the Balaka district of Malawi: A cross-sectional study - Keller, Luise; Stelzle, Dominik; Schmidt, Veronika; Carabin, Hélène; Reinhold, Ann Kristin; Keller, Claudius; Welte, Tamara; Richter, Vivien; Amos, Action; Boeckman, Lindsay; Harrison, Wendy; Winkler, Andrea S. (Plos Neglected Tropical Diseases, 2022)
BACKGROUND: Epilepsy and neurocysticercosis (NCC) prevalence estimates in sub-Saharan Africa are still scarce but show important variation due to the population studied and different screening and diagnosis strategies used. The aims of this study were to estimate the prevalence of epileptic seizures and epilepsy in the sampled population, and the proportion of NCC among people with epilepsy (PWE) in a large cross-sectional study in a rural district of southern Malawi. METHODS: We conducted a community-based door-to-door screening study for epileptic seizures in Balaka, Malawi between October and December 2012. Past epileptic seizures were reported through a 15-item questionnaire answered by at least one person per household generating five major criteria. People who screened positive were further examined by a neurologist to establish diagnosis. Patients diagnosed with epilepsy were examined and offered Taenia solium cyst antigen and antibody serological tests, and a CT scan for the diagnosis of NCC. RESULTS: In total, screening information on 69,595 individuals was obtained for lifetime occurrence of epileptic seizures. 3,100 (4.5%) participants screened positive, of whom 1,913 (62%) could be followed-up and underwent further assessment. Lifetime prevalence was 3.0% (95% Bayesian credible interval [CI] 2.8 to 3.1%) and 1.2% (95¼I 0.9 to 1.6%) for epileptic seizures and epilepsy, respectively. NCC prevalence among PWE was estimated to be 4.4% (95¼I 0.8 to 8.5%). A diagnosis of epilepsy was ultimately reached for 455 participants. CONCLUSION: The results of this large community-based study contribute to the evaluation and understanding of the burden of epilepsy in the population and of NCC among PWE in sub-Saharan Africa.
CRIS-Team Scopus Importer:2022-09-30

Comparative Socioeconomic Study Of Patients In Germany With Dravet Syndrome, Refractory Epilepsy Or Epilepsy In Seizure Remission, And Their Caregivers - Strzelczyk, A.; Schubert-Bast, S.; Bast, T.; Bettendorf, U.; Hamer, Hajo; Herting, A.; Kalski, M.; Kay, L.; Kieslich, M.; Klein, K. M.; Kluger, G.; Kurlemann, G.; et al. (EPILEPSIA, 2019)
CRIS-Team WoS Importer:2019-11-15

Comparing sparse inertial sensor setups for sagittal-plane walking and running reconstructions - Dorschky, Eva; Nitschke, Marlies; Mayer, Matthias; Weygers, Ive; Gaßner, Heiko; Seel, Thomas; Eskofier, Björn; Koelewijn, Anne (Frontiers in Bioengineering and Biotechnology, 2025)
Estimating spatiotemporal, kinematic, and kinetic movement variables with little obtrusion to the user is critical for clinical and sports applications. One possible approach is using a sparse inertial sensor setup, where sensors are not placed on all relevant body segments. Here, we investigated if movement variables can be estimated similarly accurate from sparse sensor setups as from a full lower-body sensor setup. We estimated the variables by solving optimal control problems with sagittal plane lower-body musculoskeletal models, in which we minimized an objective that combined tracking of accelerometer and gyroscope data with minimizing muscular effort. We created simulations for 10 participants at three walking and three running speeds, using seven sensor setups with between two and seven sensors located at the feet, shank, thighs, and/or pelvis. We found that differences between variables estimated from inertial sensors and those from optical motion capture were small for all sensor setups. Including all sensors did not necessarily lead to the smallest root mean square deviations (RMSDs) and highest coefficients of determination ( (Formula presented.) ). Setups without a pelvis sensor led to too much forward trunk lean and inaccurate spatiotemporal variables. Mean RMSDs were highest for the setup with two foot-worn inertial sensors (largest error in knee angle during running: 18 deg vs. 11 deg for the full lower-body setup), and ranged between 4.8–18 deg for the joint angles, between 1.0–5.4 BW BH% for the joint moments, and between 0.03 BW–0.49 BW for the ground reaction forces. We found strong or moderate relationships ( (Formula presented.) ) on average for all kinematic and kinetic variables, except for the hip and knee moment for five out of the seven setups. The large range of the coefficient of determination for most kinetic variables indicated individual differences in simulation quality. Therefore, we conclude that we can perform a comprehensive sagittal-plane motion analysis with sparse sensor setups as accurately as with a full sensor setup with sensors on the feet and on either the pelvis or the thighs. Such a sparse sensor setup enables comprehensive movement analysis outside the laboratory, by increasing usability of inertial sensors.
CRIS-Team Scopus Importer:2025-03-14
Keywords: gait analysis; gait simulations; inertial measurement units; optimal control; trajectory optimization

Comparing the effects of isocaloric oral and i.v. application of nutrient solutions on olfactory functioning - Bachlechner, Stephan; Denzer-Lippmann, M.; Wielopolski, Jan; Fische, Mr; Büttner, Andrea; Dörfler, Arnd; Schöfl, Christof; Münch, Georg; Kornhuber, Johannes; Thürauf, Norbert (2016)
EVALuna2:33154

Comparison of different normalization strategies for the analysis of glomerular microRNAs in IgA nephropathy - Bockmeyer, Clemens L.; Saeuberlich, Karen; Wittig, Juliane; Esser, Marc; Röder, Sebastian; Vester, Udo; Hoyer, Peter F.; Agustian, Putri A.; Zeuschner, Philip; Amann, Kerstin Ute; Daniel, Christoph; Becker, Jan U. (Scientific Reports, 2016)
Small nucleolar RNAs (snoRNAs) have been used for normalization in glomerular microRNA (miRNA) quantification without confirmation of validity. Our aim was to identify glomerular reference miRNAs in IgA nephropathy. We compared miRNAs in human paraffin-embedded renal biopsies from patients with cellular-crescentic IgA-GN (n = 5; crescentic IgA-GN) and non-crescentic IgA-GN (n = 5; IgA-GN) to mild interstitial nephritis without glomerular abnormalities (controls, n = 5). Laser-microdissected glomeruli were used for expression profiling of 762 miRNAs by low-density TaqMan arrays (cards A and B). The comparison of different normalization methods (GeNormPlus, NormFinder, global mean and snoRNAs) in crescentic IgA-GN, IgA-GN and controls yielded similar results. However, levels of significance and the range of relative expression differed. In median, two normalization methods demonstrated similar results. GeNormPlus and NormFinder gave different top ranked reference miRNAs. Stability ranking for snoRNAs varied between cards A and B. In conclusion, we suggest the geometric mean of the most stable reference miRNAs found in GeNormPlus (miR-26b-5p), NormFinder (miR-28-5p) and snoRNAs (RNU44) as reference. It should be considered that significant differences could be missed using one particular normalization method. As a starting point for glomerular miRNA studies in IgA nephropathy we provide a library of miRNAs.
EVALuna2:25525

Comparison of scoring tools for the prediction of in-hospital mortality in status epilepticus - Reindl, Caroline; Knappe, Ruben U.; Sprügel, Maximilian; Sembill, Jochen; Müller, Tamara; Hamer, Hajo; Huttner, Hagen; Madzar, Dominik (Seizure-European Journal of Epilepsy, 2018)
PURPOSE: Several scoring tools have been developed for the prognostication of outcome after status epilepticus (SE). In this study, we compared the performances of STESS (Status Epilepticus Severity Score), mSTESS (modified STESS), EMSE-EAL (Epidemiology-based Mortality Score in Status Epilepticus- Etiology, Age, Level of Consciousness) and END-IT (Encephalitis-NCSE-Diazepam resistance-Image abnormalities-Tracheal intubation) in predicting in-hospital mortality after SE. METHOD: Data collected retrospectively from a cohort of 287 patients with SE were used to calculate STESS, mSTESS, EMSE-EAL, and END-IT scores. The differences between the scores' performances were determined by means of area under the ROC curve (AUC) comparisons and McNemar testing. RESULTS: The in-hospital mortality rate was 11.8%. The AUC of STESS (0.628; 95% confidence interval (CI), 0.529-0.727) was similar to that of mSTESS (0.620; 95% CI, 0.510-0.731), EMSE-EAL (0.556; 95% CI, 0.446-0.665), and END-IT (0.659; 95% CI, 0.550-0.768; p > .05 for each comparison) in predicting in-hospital mortality. STESS with a cutoff of 3 was found to have lowest specificity and number of correctly classified episodes. EMSE-EAL with a cutoff at 40 had highest specificity and showed a trend towards more correctly classified episodes while sensitivity tended to be low. END-IT with a cutoff of 3 had the most balanced sensitivity-specificity ratio. CONCLUSIONS: EMSE-EAL is as easy to calculate as STESS and tended towards higher diagnostic accuracy. Adding information on premorbid functional status to STESS did not enhance outcome prediction. END-IT was not superior to other scores in prediction of in-hospital mortality despite including information of diagnostic work-up and response to initial treatment.
EVALuna2:201931

Comparison of Two Automated Computed Tomography Perfusion Applications to Predict the Final Infarct Volume After Thrombolysis in Cerebral Infarction 3 Recanalization - Mühlen, Iris; Sprügel, Maximilian; Hölter, Philip; Hock, Stefan; Knott, Michael; Huttner, Hagen; Schwab, Stefan; Kallmünzer, Bernd; Dörfler, Arnd (Stroke, 2022)
Background: Several automated computed tomography perfusion software applications have been developed to provide support in the definition of ischemic core and penumbra in acute ischemic stroke. However, the degree of interchangeability between software packages is not yet clear. Our study aimed to evaluate 2 commonly used automated perfusion software applications (Syngo.via and RAPID) for the indication of ischemic core with respect to the follow-up infarct volume (FIV) after successful recanalization and with consideration of the clinical impact. Methods: Retrospectively, 154 patients with large vessel occlusion of the middle cerebral artery or the internal carotid artery, who underwent endovascular therapy with a consequent Thrombolysis in Cerebral Infarction 3 result within 2 hours after computed tomography perfusion, were included. Computed tomography perfusion core volumes were assessed with both software applications with different thresholds for relative cerebral blood flow (rCBF). The results were compared with the FIV on computed tomography within 24 to 36 hours after recanalization. Bland-Altman was applied to display the levels of agreement and to evaluate systematic differences. Results: Highest correlation between ischemic core volume and FIV without significant differences was found at a threshold of rCBF<38% for the RAPID software (r=0.89, P<0.001) and rCBF<25% for the Syngo software (r=0.87, P<0.001). Bland-Altman analysis revealed best agreement in these settings. In the vendor default settings (rCBF<30% for RAPID and rCBF<20% for Syngo) correlation between ischemic core volume and FIV was also high (RAPID: r=0.88, Syngo: r=0.86, P<0.001), but mean differences were significant (P<0.001). The risk of critical overestimation of the FIV was higher with rCBF<38% (RAPID) and rCBF<25% (Syngo) than in the default settings. Conclusions: By adjusting the rCBF thresholds, comparable results with reliable information on the FIV after complete recanalization can be obtained both with the RAPID and Syngo software. Keeping the software specific default settings means being more inclusive in patient selection, but forgo the highest possible accuracy in the estimation of the FIV.
CRIS-Team WoS Importer:2022-05-13

COMPASS 31 bladder sub-scores correlate with uroflow parameters in patients with relapsing-remitting multiple sclerosis - Wang, Ruihao; Fröhlich, Kilian; Winder, Klemens; Singer, W.; Lee, D.; Linker, R.; Hilz, Max-Josef (EUROPEAN JOURNAL OF NEUROLOGY, 2022)
CRIS-Team WoS Importer:2022-07-22

Compensatory neuritogenesis of serotonergic afferents within the striatum of a transgenic rat model of Parkinson's disease - Stemick, Judith; Gauer, Carina; Wihan, Jeanette; Moceri, Sandra; Xiang, Wei; von Hörsten, Stephan; Kohl, Zacharias; Winkler, Jürgen (Brain Research, 2020)
The majority of patients with Parkinson's disease (PD) suffer from L-DOPA-induced dyskinesia (LID). Besides a dysfunctional dopaminergic system, changes of the serotonergic network may be linked to this severe and adverse symptom. Particularly, serotonergic neurons have the potential to synthesize dopamine, likely associated with a disproportional dopamine release within the striatum. We hypothesized that the serotonergic system is adaptively altered in the striatum due to the reduced dopaminergic input. To answer this question, we analyzed a transgenic rat PD model ubiquitously expressing human α-synuclein using a bacterial artificial chromosome. Neurite analysis showed a profound loss of dopaminergic fibers by 30–40% within the dorsal striatum paralleled by a 50% reduction of dopaminergic neurons in the substantia nigra pars compacta. In contrast, serotonergic fibers showed an increased fiber density in the dorsal striatum by 100%, while the number of serotonergic neurons within the raphe nuclei (RN) and its proximal neuritic processes were unaffected. Furthermore, both the dopaminergic and serotonergic fiber density remained unchanged in the neighboring motor cortex M1/M2. Interestingly, essential enzymes required for L-DOPA turnover and dopamine release were expressed in serotonergic neurons of the RN. In parallel, the serotonergic autoreceptor levels involved in a serotonergic negative feedback loop were reduced within the striatum, suggesting a dysfunctional neurotransmitter release. Overall, the increased serotonergic fiber density with its capacity for dopamine release within the striatum suggests a compensatory, site-specific serotonergic neuritogenesis. This maladaptive serotonergic plasticity may be linked to adverse symptoms such as LIDs in PD.
CRIS-Team Scopus Importer:2020-10-02
Keywords: Dopamine; L-DOPA-induced dyskinesia; Parkinson's disease; Serotonin; Striatum; α-synuclein

Comprehensive Multimodal Deep Learning Survival Prediction Enabled by a Transformer Architecture: A Multicenter Study in Glioblastoma - Gomaa, Ahmed; Huang, Yixing; Hagag, Amr; Schmitter, Charlotte; Höfler, Daniel; Weissmann, Thomas; Breininger, Katharina; Schmidt, Manuel; Stritzelberger, Jenny; Delev, Daniel; Coras, Roland; Dörfler, Arnd; et al. (Neuro-Oncology Advances, 2024)
Keywords: Survival prediction; deep learning; glioblastoma; MR; prognosis; multimodal data

Comprehensive visualization of paresthesia in breast cancer survivors - Jud, Sebastian; Hatko, Reinhard; Maihoefner, Christian; Bani, Mayada; Schrauder, Michael G.; Lux, Michael P.; Beckmann, Matthias; Bani, Gassan; Eder, Irina; Fasching, Peter; Löhberg, Christian; Rauh, Claudia; et al. (Archives of Gynecology and Obstetrics, 2014)
As breast cancer survivors are benefiting increasingly from advanced forms of therapy, the side effects of locoregional treatment in the adjuvant setting are becoming more and more important. This article presents a new method of assessing the spatial distribution of paresthesia in breast cancer survivors after different locoregional treatments.A structured questionnaire assessing paresthesia, with body pictograms for marking paresthesia areas, was completed by 343 breast cancer survivors. The image information was digitized, generating gray-scale summation images with numbers from 0, indicating black (100 % of the patients had paresthesia), to 255, indicating white (none had paresthesia). The resulting map visualization showed the locations of paresthesia on body pictograms. The group included patients who had undergone breast-conserving surgery (BCS) and mastectomy, and also patients who had received percutaneous and interstitial radiation.A total of 56.5 % of the patients stated that they had paresthesia. The paresthesia areas were distributed within the range suggested by clinical experience. Most patients stated that they had paresthesia in the upper outer quadrant and axilla. Patients who had undergone mastectomy or percutaneous radiotherapy appeared to have more paresthesia on some areas of the body surface. Patients who had undergone mastectomy indicated larger areas of paresthesia than those with BCS-4,066 pixels (px) vs. 2,275 px. Radiotherapy did not appear to influence the spatial distribution of paresthesia.Paresthesia is a common symptom after breast cancer treatment. This paper describes a new method of assessing this side effect to improve and individualize treatment for it in the future.
EVALuna2:17450

Compromised cardiovascular autonomic modulation in patient with acute ischemic stroke improves after three & six months - Wang, Ruihao; Macha, Kosmas; Köhn, Julia; Köhn, Julia; Siedler, Gabriela; Winder, Klemens; Gerner, Stefan; Schwab, Stefan; Koehrmann, M.; Kallmünzer, Bernd; Hilz, Max-Josef (EUROPEAN JOURNAL OF NEUROLOGY, 2021)
CRIS-Team WoS Importer:2021-07-23

Connecting real-world digital mobility assessment to clinical outcomes for regulatory and clinical endorsement–the Mobilise-D study protocol - Mikolaizak, A. Stefanie; Rochester, Lynn; Maetzler, Walter; Sharrack, Basil; Demeyer, Heleen; Mazzà, Claudia; Caulfield, Brian; Garcia-Aymerich, Judith; Vereijken, Beatrix; Arnera, Valdo; Miller, Ram; Piraino, Paolo; et al. (PLoS ONE, 2022)
Background The development of optimal strategies to treat impaired mobility related to ageing and chronic disease requires better ways to detect and measure it. Digital health technology, including body worn sensors, has the potential to directly and accurately capture real-world mobility. Mobilise-D consists of 34 partners from 13 countries who are working together to jointly develop and implement a digital mobility assessment solution to demonstrate that real-world digital mobility outcomes have the potential to provide a better, safer, and quicker way to assess, monitor, and predict the efficacy of new interventions on impaired mobility. The overarching objective of the study is to establish the clinical validity of digital outcomes in patient populations impacted by mobility challenges, and to support engagement with regulatory and health technology agencies towards acceptance of digital mobility assessment in regulatory and health technology assessment decisions. Methods/design The Mobilise-D clinical validation study is a longitudinal observational cohort study that will recruit 2400 participants from four clinical cohorts. The populations of the Innovative Medicine Initiative-Joint Undertaking represent neurodegenerative conditions (Parkinson’s Disease), respiratory disease (Chronic Obstructive Pulmonary Disease), neuro-inflammatory disorder (Multiple Sclerosis), fall-related injuries, osteoporosis, sarcopenia, and frailty (Proximal Femoral Fracture). In total, 17 clinical sites in ten countries will recruit participants who will be evaluated every six months over a period of two years. A wide range of core and cohort specific outcome measures will be collected, spanning patient-reported, observer-reported, and clinician-reported outcomes as well as performance-based outcomes (physical measures and cognitive/mental measures). Daily-living mobility and physical capacity will be assessed directly using a wearable device. These four clinical cohorts were chosen to obtain generalizable clinical findings, including diverse clinical, cultural, geographical, and age representation. The disease cohorts include a broad and heterogeneous range of subject characteristics with varying chronic care needs, and represent different trajectories of mobility disability. Discussion The results of Mobilise-D will provide longitudinal data on the use of digital mobility outcomes to identify, stratify, and monitor disability. This will support the development of widespread, cost-effective access to optimal clinical mobility management through personalised healthcare. Further, Mobilise-D will provide evidence-based, direct measures which can be endorsed by regulatory agencies and health technology assessment bodies to quantify the impact of disease-modifying interventions on mobility.
CRIS-Team Scopus Importer:2022-10-21

Consensus based framework for digital mobility monitoring - Kluge, Felix; Del Din, Silvia; Cereatti, Andrea; Gaßner, Heiko; Hansen, Clint; Helbostad, Jorunn L.; Klucken, Jochen; Küderle, Arne; Mueller, Arne; Rochester, Lynn; Ullrich, Martin; Eskofier, Björn; et al. (PLoS ONE, 2021)
Digital mobility assessment using wearable sensor systems has the potential to capture walking performance in a patient's natural environment. It enables monitoring of health status and disease progression and evaluation of interventions in real-world situations. In contrast to laboratory settings, real-world walking occurs in non-conventional environments and under unconstrained and uncontrolled conditions. Despite the general understanding, there is a lack of agreed definitions about what constitutes real-world walking, impeding the comparison and interpretation of the acquired data across systems and studies. The goal of this study was to obtain expert-based consensus on specific aspects of real-world walking and to provide respective definitions in a common terminological framework. An adapted Delphi method was used to obtain agreed definitions related to real-world walking. In an online survey, 162 participants from a panel of academic, clinical and industrial experts with experience in the field of gait analysis were asked for agreement on previously specified definitions. Descriptive statistics was used to evaluate whether consent (> 75% agreement as defined a priori) was reached. Of 162 experts invited to participate, 51 completed all rounds (31.5% response rate). We obtained consensus on all definitions ("Walking" > 90%, "Purposeful" > 75%, "Real-world" > 90%, "Walking bout" > 80%, "Walking speed" > 75%, "Turning" > 90% agreement) after two rounds. The identification of a consented set of real-world walking definitions has important implications for the development of assessment and analysis protocols, as well as for the reporting and comparison of digital mobility outcomes across studies and systems. The definitions will serve as a common framework for implementing digital and mobile technologies for gait assessment and are an important link for the transition from supervised to unsupervised gait assessment.
CRIS-Team WoS Importer:2021-09-03

Consensus statement on the definition of neurogenic supine hypertension in cardiovascular autonomic failure by the American Autonomic Society (AAS) and the European Federation of Autonomic Societies (EFAS) : Endorsed by the European Academy of Neurology (EAN) and the European Society of Hypertension (ESH) - Fanciulli, Alessandra; Jordan, Jens; Biaggioni, Italo; Calandra-Buonaura, Giovanna; Cheshire, William P.; Cortelli, Pietro; Eschlboeck, Sabine; Grassi, Guido; Hilz, Max-Josef; Kaufmann, Horacio; Lahrmann, Heinz; Mancia, Giuseppe; et al. (Clinical Autonomic Research, 2018)
PURPOSE: Patients suffering from cardiovascular autonomic failure often develop neurogenic supine hypertension (nSH), i.e., high blood pressure (BP) in the supine position, which falls in the upright position owing to impaired autonomic regulation. A committee was formed to reach consensus among experts on the definition and diagnosis of nSH in the context of cardiovascular autonomic failure. METHODS: As a first and preparatory step, a systematic search of PubMed-indexed literature on nSH up to January 2017 was performed. Available evidence derived from this search was discussed in a consensus expert round table meeting in Innsbruck on February 16, 2017. Statements originating from this meeting were further discussed by representatives of the American Autonomic Society and the European Federation of Autonomic Societies and are summarized in the document presented here. The final version received the endorsement of the European Academy of Neurology and the European Society of Hypertension. RESULTS: In patients with neurogenic orthostatic hypotension, nSH is defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, measured after at least 5 min of rest in the supine position. Three severity degrees are recommended: mild, moderate and severe. nSH may also be present during nocturnal sleep, with reduced-dipping, non-dipping or rising nocturnal BP profiles with respect to mean daytime BP values. Home BP monitoring and 24-h-ambulatory BP monitoring provide relevant information for a customized clinical management. CONCLUSIONS: The establishment of expert-based criteria to define nSH should standardize diagnosis and allow a better understanding of its epidemiology, prognosis and, ultimately, treatment.
EVALuna2:213464

Consensus statements and recommendations from the ESO-Karolinska Stroke Update Conference, Stockholm 11-13 November 2018 - Ahmed, Niaz; Audebert, Heinrich; Turc, Guillaume; Cordonnier, Charlotte; Christensen, Hanne; Sacco, Simona; Sandset, Else Charlotte; Ntaios, George; Charidimou, Andreas; Toni, Danilo; Pristipino, Christian; Köhrmann, Martin; et al. (European Stroke Journal, 2019)
The purpose of the European Stroke Organisation-Karolinska Stroke Update Conference is to provide updates on recent stroke therapy research and to give an opportunity for the participants to discuss how these results may be implemented into clinical routine. The meeting started 22 years ago as Karolinska Stroke Update, but since 2014 it is a joint conference with European Stroke Organisation. Importantly, it provides a platform for discussion on the European Stroke Organisation guidelines process and on recommendations to the European Stroke Organisation guidelines committee on specific topics. By this, it adds a direct influence from stroke professionals otherwise not involved in committees and work groups on the guideline procedure. The discussions at the conference may also inspire new guidelines when motivated. The topics raised at the meeting are selected by the scientific programme committee mainly based on recent important scientific publications. This year's European Stroke Organisation-Karolinska Stroke Update Meeting was held in Stockholm on 11-13 November 2018. There were 11 scientific sessions discussed in the meeting including two short sessions. Each session except the short sessions produced a consensus statement (Full version with background, issues, conclusions and references are published as web-material and at and ) and recommendations which were prepared by a writing committee consisting of session chair(s), scientific secretary and speakers. These statements were presented to the 250 participants of the meeting. In the open meeting, general participants commented on the consensus statement and recommendations and the final document were adjusted based on the discussion from the general participants Recommendations (grade of evidence) were graded according to the 1998 Karolinska Stroke Update meeting with regard to the strength of evidence. Grade A Evidence: Strong support from randomised controlled trials and statistical reviews (at least one randomised controlled trial plus one statistical review). Grade B Evidence: Support from randomised controlled trials and statistical reviews (one randomised controlled trial or one statistical review). Grade C Evidence: No reasonable support from randomised controlled trials, recommendations based on small randomised and/or non-randomised controlled trials evidence.
CRIS-Team WoS Importer:2019-09-24

Consistent Value of Two-Stage Pedicle Flaps in the Age of Microsurgical Maxillofacial Reconstruction - Frohwitter, Gesche; Lutz, Rainer; Baran, Christoph; Weber, Margarete; Nobis, Christopher-Philipp; Rau, A.; Kesting, Marco Rainer (Journal of Maxillofacial and Oral Surgery, 2021)
Introduction: Up to the second half of the twentieth century, pedicled flaps marked the gold standard in reconstructive surgery. Followed by the introduction of microsurgical techniques, these flaps were increasingly abandoned. We conducted a retrospective study to determine the value of two-stage pedicle flaps in modern maxillofacial reconstruction. Material & Methods: A chart review from October 2017 to November 2020 was performed to identify patients who were treated by a two-stage pedicle flap in our Department of Oral and Maxillofacial Surgery. Results: A total of 31 patients, 17 female and 14 males received 36 two-stage pedicle flaps. All patients were in noticeably impaired health condition with a majority of ASA-score 3. The defect location mainly contained extraoral resections (58.3%). A variety of flaps were harvested consisting of buccal flaps, Abbe flaps, forehead flaps, deltopectoral flaps, nasolabial flaps, and a tubed flap. Discussion: The study outlines two indications for the use of two-stage pedicle flaps. Firstly, as a back-up strategy in heavily pre-treated wound beds and secondly in an almost contrarily indication as a first-choice reconstructive option of the facial skin in esthetic demanding cases. Conclusion: The timesaving and straight forward surgical approach as well as their low postsurgical complications and strong long-time success rates secure the two-stage pedicle flap a justified niche role in times of microsurgical maxillofacial reconstruction.
CRIS-Team Scopus Importer:2021-09-03
Keywords: Back-up procedures; Pedicle flaps; Reconstructive surgery; Transplant autonomy

Contactless Heart Rate Estimation using a 61 GHz Continuous-Wave Radar - Krauß, Daniel; Richer, Robert; Albrecht, Nils Christian; Küderle, Arne; Abel, Luca; Leutheuser, Heike; Jukic, Jelena; German, Alexander; Kölpin, Alexander; Winkler, Jürgen; Eskofier, Björn (IEEE-EMBS International Conference on Body Sensor Networks: Sensor and Systems for Digital Health, 2023)
I. INTRODUCTION According to estimations by the World Health Organization, more than 8.5 million people are diagnosed with Parkinson’s disease, making it the second most prevalent neurodegenerative disorder worldwide [1]. While the most commonly-known symptoms are motor symptoms, the disease is also characterized by sleep-related non-motor symptoms such as rapid- eye-movement sleep behavior disorder, insomnia, or daytime sleepiness. Therefore, reliable sleep monitoring is crucial for the diagnosis and treatment. As traditional sleep monitoring is obtrusive and hard to perform longitudinally, the contactless measurement of biosignals at home is a promising alternative for meaningful analysis of sleep [2]. Previous research has shown encouraging results in the extraction of relevant biosignals such as heart sounds or respi- ration waves from radar data [3]. However, there is insufficient research on assessing the robustness against different sleeping positions, as well as the combination of multiple radar sensors. For that reason, this work aims to present a radar sens- ing system for nocturnal heart sound extraction using a bi- directional Long short-term memory network. In particular, we combine the information collected by four radar sensors placed horizontally at thorax height under the bed mattress. Furthermore, we compared the extracted heart rate with respect to different sleeping positions and upright sitting. II. METHODS The data used in this work were obtained from an overnight sleep study of 17 participants (age: 27.6 ± 8.4; 52.9% female), resulting in a total of 99.5 hours of sleep data. The dataset includes polysomnography recordings and simultaneous sig- nals captured by four 61 GHz continuous wave doppler radars. For each radar sensor, heart sounds were extracted from the raw signals using a pre-trained bi-directional LSTM model. On the model output, we performed a threshold-based peak detection to identify individual heart beats. To fuse the output of the four sensors, we selected the sensor with the highest number of detected heart beats for every 30-second window. Subsequently, the selected beats were utilized to calculate the mean heart rate, which was then compared with the heart rate extracted from the electrocardiogram data for each respective 30-second window. III. RESULTS & DISCUSSION Our results show that the mean absolute error of the extracted heart rate is 1.53 ± 2.14 bpm (Table 1). This performance is consistent across right, left, supine, or prone pose. Only when participants were sitting in the bed, the extraction performance dropped noticeably. However, this posture is not relevant for the analysis of specific sleep patterns. Our findings underline the potential of contactless vital sign monitoring for unobtrusive sleep analysis. This allows for longitudinal and more realistic measurements of sleep patterns. Thus, it is a promising step towards transferring sleep labora- tories into a home monitoring environment.

Contrast-enhanced angiographic computed tomography for detection of aneurysm remnants after clipping: a comparison with digital subtraction angiography in 112 clipped aneurysms - Gölitz, Philipp; Struffert, Tobias; Ganslandt, Oliver Thomas; Lang, Stefan; Knossalla, Frauke; Dörfler, Arnd (Neurosurgery, 2014)
For preclusion of remnants after aneurysm clipping, a reliable, noninvasive imaging technique is desirable.To evaluate the reliability of optimized angiographic computed tomography with intravenous contrast agent injection (ivACT) in detecting remnants after aneurysmal clipping compared with digital subtraction angiography (DSA), the gold standard.We included 84 patients with 112 clipped cerebral aneurysms of the anterior circulation. For treatment, 116 clips of cobalt and 57 clips of titanium alloy were used. In each patient, we performed an ivACT with dual rotational acquisition and a DSA. Data from ivACT were postprocessed with a dual-volume technique with newly implemented reconstructions modes. Aneurysm remnants were measured, classified, and correlated with DSA by 2 raters.In total, 12 remnants were revealed by DSA, meaning a prevalence of 11%. IvACT demonstrated a sensitivity of 75% to 92% and a specificity of 99% in detecting remnants up to a minimal size of 0.7 × 0.3 mm. Classification of remnants by ivACT was identical to that by DSA, and assessment of size showed a significant correlation with DSA (P < .001). No significant differences between cobalt and titanium alloy were revealed concerning artifacts.Optimized ivACT with enhanced postprocessing demonstrated high sensitivity and specificity in detecting remnants after aneurysm clipping in the anterior circulation. Classification and assessment of remnant size and detection of relevant parent artery stenosis showed high accuracy of ivACT compared with DSA. Our results indicate that ivACT might become a noninvasive alternative to DSA for postsurgical control.
EVALuna2:22328

Co-occurrence of antibodies against dipeptidyl-peptidase-like protein-6 and aquaporin-4 during a case of paraneoplastic encephalitis - Bien, Christian G.; Schänzer, Anne; Dargvainiene, Justina; Dogan-Onugoren, Muejgan; Woermann, Friedrich; Strickler, Alexander (Clinical Neurology and Neurosurgery, 2020)
CRIS-Team Scopus Importer:2020-07-31
Keywords: Aquaporin-4 antibodies; DPPX antibodies; Encephalitis; Encephalomyelitis; Paraneoplastic neurological syndrome

Cooling in intracerebral hemorrhage (CINCH) trial: Protocol of a randomized German-Austrian clinical trial - Kollmar, Rainer; Juettler, Eric; Huttner, Hagen; Dörfler, Arnd; Staykov, Dimitre; Kallmünzer, Bernd; Schmutzhard, Erich; Schwab, Stefan; Broessner, Gregor (International Journal of Stroke, 2012)
Background: Intracerebral hemorrhage accounts for up to 15% of all strokes and is frequently associated with poor functional outcome and high mortality. So far, there is no clear evidence for a specific therapy, apart from general stroke unit or neurointensive care and management of secondary complications. Promising experimental and pilot clinical data support the use of therapeutic hypothermia after intracerebral hemorrhage. Aims: The study aims to determine if therapeutic hypothermia improves survival rates and reduces cerebral lesion volume after large intracerebral hemorrhage compared with conventional treatment. Material and methods: The Cooling in IntraCerebral Hemorrhage trial is a prospective, multicenter, interventional, randomized, parallel, two-arm (1:1) phase II trial with blinded end-point adjudication. Enrolment: 50 patients (age: 18 to 65 years) with large (25 to 64ml on cranial computertomography), primary intracerebral hemorrhage of the basal ganglia or thalamus within 6 to 18h after symptom onset are randomly allocated to therapeutic hypothermia for eight-days or conventional temperature management. In the therapeutic hypothermia group, a target temperature of 35·0°C is achieved by endovascular catheters and followed by slow controlled rewarming. Data analysis is based on the intent-to-treat population. The primary outcome measure of the study is the development in total lesion volume on cranial computertomography (intracerebral hemorrhage plus perihemorrhagic edema on day 8±0·5 and day 11±0·5 after intracerebral hemorrhage) and the mortality after 30 days. Secondary end-points are the in-hospital mortality, mortality, and functional outcome (modified Rankin Scale and Barthel-Index) after 90 and 180 days. Safety measures include any adverse events associated with therapeutic hypothermia. Discussion: In the face of a lack of evidence-based therapies for patients with large intracerebral hemorrhage, new promising approaches are desperately needed, but need evaluation in randomized controlled trials. Conclusion: The results of Cooling in IntraCerebral Hemorrhage trial are believed to directly influence future therapy of large intracerebral hemorrhage. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Edema; Hypothermia; Intracerebral hemorrhage; Neuroprotection; Stroke

Coregistrating magnetic source and magnetic resonance imaging for epilepsy surgery in focal cortical dysplasia - Kasper, Burkhard; Roessler, Karl; Hamer, Hajo; Dörfler, Arnd; Blümcke, Ingmar; Coras, Roland; Rösch, Julie; Mennecke, Angelika; Wellmer, Joerg; Sommer, Bjoern; Lorber, Bogdan; Lang, Johannes D.; et al. (NeuroImage: Clinical, 2018)
Background: Epilepsy surgery for focal cortical dysplasia type II (FCD II) offers good chances for seizure freedom, but remains a challenge with respect to lesion detection, defining the epileptogenic zone and the optimal resection strategy. Integrating results from magnetic source imaging from magnetoencephalography (MEG) with magnetic resonance imaging (MRI) including MRI postprocessing may be useful for optimizing these goals. Methods: We here present data from 21 adult FCD II patients, investigated during a 10 year period and evaluated including magnetic source imaging. 16 patients had epilepsy surgery, i.e. histopathologically verified FCD II, and a long follow up. We present our analysis of epileptogenic zones including MEG in relation to structural data according to MRI data and relate these results to surgical outcomes. Results: FCD II in our cohort was characterized by high MEG yield and localization accuracy and MEG showed impact on surgical success-rates. MEG source localizations were detected in 95.2% of patients and were as close as 12.3 ± 8,1 mm to the MRI-lesion. After a mean follow up of >3 years, we saw >80% Engel I outcomes, with more favourable outcomes when the MEG source was completely resected (Fishers exact test 0,033). Conclusion: We argue for a high value of conducting a combined MEG-MRI approach in the presurgical workup and the resection strategy in patients with FCD II related epilepsy.
EVALuna2:35523

Correction to: Clinical characterization of common pathogenic variants of SOD1-ALS in Germany (Journal of Neurology, (2024), 271, 10, (6667-6679), 10.1007/s00415-024-12564-1) - Wiesenfarth, Maximilian; Forouhideh-Wiesenfarth, Yalda; Elmas, Zeynep; Parlak, Özlem; Weiland, Ulrike; Herrmann, Christine; Schuster, Joachim; Freischmidt, Axel; Müller, Kathrin; Siebert, Reiner; Günther, Kornelia; Fröhlich, Elke; et al. (Journal of Neurology, 2025)
In the original version of this article, the disease progression rates (ALSFRS-R between onset and last visit) were not reported in points lost per month as described in the text, but in points lost per week (in the text, Tables 2, 3 and Fig. 1b). This affects the progression rates in the text, Tables 2, 3 and Fig. 1b. In the abstract, fifth sentence which previously read Moreover, R116G patients had the fastest median ALSFRS-R progression rate with 0.12 (IQR 0.07–0.20) points lost per month. Should have read Moreover, R116G patients had the fastest median ALSFRS-R progression rate with 0.51 (IQR 0.28–0.87) points lost per month. In the section “ALSFRS‑R, progression rate and diagnostic delay” first paragraph which previously read Consistent with the survival data, SOD1-ALS patients with R116G variants showed a median disease progression rate of 0.12 ALSFRS-R points lost per month (IQR 0.07–0.20) between onset and last visit, which was more pronounced compared to patients with pathogenic D91A (0.03, IQR 0.02–0.08; n = 8; p = 0.02) and L145F variants (median 0.06, IQR 0.04–0.14; n = 6; p = 0.21), while D91A and L145F patients showed a quite similar, slow median progression rate (p = 0.35; Fig. 1b). Moreover, these differences in ALSFRS-R progression rate were already detected in an early phase of the disease, as a decline of 0.62 points (IQR 0.25–0.76; n = 14) per month in ALSFRS-R was found in patients with R116G variants compared to 0.16 (IQR 0.09–0.44; n = 8; p = 0.04) in patients with D91A and 0.38 with L145F variants (IQR 0.14–1.05; n = 6; p = 0.73) between the onset of the disease and the first visit at a MND reference center. In line with this faster disease progression, also the median delay of ALS diagnosis in patients carrying R116G variants was shorter (median 10.0 months, IQR 5.5–11.5; n = 13) than in patients with D91A (median 57.5 months, IQR 14.0–83.0; n = 6; p < 0.001) and in patients with L145F variants (median 21.5 months, IQR 5.8–38.8; n = 4; p = 0.27; Fig. 1c). Of note, median ALSFRS-R progression rates in patients with R116G, D91A and L145F were lower compared to patients carrying less frequent SOD1 variants (0.50, IQR 0.13–1.38; n = 32; Table 2). Median ALSFRS-R at first visit was 42.5 (IQR 39.0–45.0; n = 14) in patients with R116G and therefore higher compared to 37.5 (IQR 32.0–40.8; n = 8) in D91A (p = 0.04; Fig. 1d) and similar to L145F carriers (43.0, IQR 23.0–45.3; n = 6; p = 0.83; Fig. 1d). Should have read Consistent with the survival data, SOD1-ALS patients with R116G variants showed a median disease progression rate of 0.51 ALSFRS-R points lost per month (IQR 0.28–0.87) between onset and last visit, which was more pronounced compared to patients with pathogenic D91A (0.14, IQR 0.08–0.33; n = 8; p = 0.02) and L145F variants (median 0.27, IQR 0.17–0.62; n = 6; p = 0.24), while D91A and L145F patients showed a quite similar, slow median progression rate (p = 0.28; Fig. 1b). Moreover, these differences in ALSFRS-R progression rate were already detected in an early phase of the disease, as a decline of 0.62 points (IQR 0.25–0.76; n = 14) per month in ALSFRS-R was found in patients with R116G variants compared to 0.16 (IQR 0.09–0.44; n = 8; p = 0.04) in patients with D91A and 0.38 with L145F variants (IQR 0.14–1.05; n = 6; p = 0.73) between the onset of the disease and the first visit at a MND reference center. In line with this faster disease progression, also the median delay of ALS diagnosis in patients carrying R116G variants was shorter (median 10.0 months, IQR 5.5–11.5; n = 13) than in patients with D91A (median 57.5 months, IQR 14.0–83.0; n = 6; p < 0.001) and in patients with L145F variants (median 21.5 months, IQR 5.8–38.8; n = 4; p = 0.27; Fig. 1c). Of note, median ALSFRS-R progression rates in patients with D91A and L145F were lower compared to patients carrying less frequent SOD1 variants (0.50, IQR 0.13–1.38; n = 32; Table 2). Median ALSFRS-R at first visit was 42.5 (IQR 39.0–45.0; n = 14) in patients with R116G and therefore higher compared to 37.5 (IQR 32.0–40.8; n = 8) in D91A (p = 0.04; Fig. 1d) and similar to L145F carriers (43.0, IQR 23.0–45.3; n = 6; p = 0.83; Fig. 1d). In the section “Clinical phenotype in patients with homozygous and heterozygous D91A allele genotype” second and third paragraph which previously read Patients carrying a D91A on both alleles, i.e. in homozygous state (n = 6) all had a spinal onset of the disease, with a mean age of onset of 53.2 years (SD ± 12.7 years; n = 6), equal shares of males and females, but a positive family history of ALS in only 33.3%. ALS was diagnosed after a diagnostic delay of 35.0 months (mean, SD ± 31.2; n = 3). At first visit patients showed a median ALSFRS-R of 41.0 (IQR 38.0–44.0; n = 4), which declined in the median 0.04 points/month (IQR 0.02–0.08) until the last visit. Two patients with homozygous allele genotype died during the observation period after 141.0 and 198.0 months, respectively. Age of onset in patients with heterozygous (n = 4) D91A allele genotype was 46.8 years (SD ± 15.5 years; n = 4). 75.0% (n = 3) of the included four patients were female and family history was also apparently negative in 75.0% (n = 3). All patients had a spinal onset of the disease. ALS was diagnosed after a mean delay of 78.0 months (SD ± 17.0 months; n = 3). ALSFRS-R was 35.0 (median, IQR 27.0–37.0; n = 4) at first visit and showed a median progression rate of 0.03 points lost/month (IQR 0.02–0.11; n = 4) until the last visit. Should have read Patients carrying a D91A on both alleles, i.e. in homozygous state (n = 6) all had a spinal onset of the disease, with a mean age of onset of 53.2 years (SD ± 12.7 years; n = 6), equal shares of males and females, but a positive family history of ALS in only 33.3%. ALS was diagnosed after a diagnostic delay of 35.0 months (mean, SD ± 31.2; n = 3). At first visit patients showed a median ALSFRS-R of 41.0 (IQR 38.0–44.0; n = 4), which declined in the median 0.17 points/month (IQR 0.07–0.33) between onset and the last visit. Two patients with homozygous allele genotype died during the observation period after 141.0 and 198.0 months, respectively. Age of onset in patients with heterozygous (n = 4) D91A allele genotype was 46.8 years (SD ± 15.5 years; n = 4). 75.0% (n = 3) of the included four patients were female and family history was also apparently negative in 75.0% (n = 3). All patients had a spinal onset of the disease. ALS was diagnosed after a mean delay of 78.0 months (SD ± 17.0 months; n = 3). ALSFRS-R was 35.0 (median, IQR 27.0–37.0; n = 4) at first visit and showed a median progression rate of 0.11 points lost/month (IQR 0.08–0.46; n = 4) between onset and the last visit. Tables 2 and 3 which previously read Table 2 Clinical features of patients with different variants of the SOD1 gene (Figure presented.) Table 3 Clinical features of ALS patients with homozygous and heterozygous SOD1 D91A genotypes (Figure presented.) Tables 2 and 3 should have read (Table presented.) (Table presented.) Clinical features of patients with different variants of the SOD1 gene R116G (n = 26) D91A (n = 10) L145F (n = 6) Others (n = 41) Age of onset (median, IQR) 52.0 (47.0–60.3) (n = 22) 50.0 (41.0–64.3) (n = 10) 54.0 (44.8–56.3) (n = 6) 48.0 (33.5–58.0) (n = 40) Male 69.2% (n = 18) 40.0% (n = 4) 66.7% (n = 4) 50.0% (n = 20) Female 30.8% (n = 8) 60.0% (n = 6) 33.3% (n = 2) 50.0% (n = 20) Spinal 100.0% (n = 18) 100.0% (n = 6) 100.0% (n = 6) 82.1% (n = 32) Bulbar 0.0% (n = 0) 0.0% (n = 0) 0.0% (n = 0) 17.9% (n = 7) Positive 96.2% (n = 25) 50.0% (n = 5) 100% (n = 6) 82.1% (n = 32) Negative 3.8% (n = 1) 50.0% (n = 5) 0% (n = 0) 17.9% (n = 7) ALSFRS-R (1st visit) (median, IQR) 42.5 (39.0–45.0) (n = 14) 37.5 (32.0–40.8) (n = 8) 43.0 (23.0–45.3) (n = 6) 38.0 (30.0–44.0) (n = 31) Progression rate (median, IQR) (onset to last visit) 0.51 (0.28–0.87) (n = 14) 0.14 (0.08–0.33) (n = 8) 0.27 (0.17–0.62) (n = 6) 0.50 (0.13–1.38) (n = 32) BMI in kg/m2 (median, IQR) 26.8 (24.9–27.7) (n = 9) 25.2 (19.8–27.4) (n = 6) 26.3 (24.4–31.1) (n = 4) 25.8 (21.9–30.5) (n = 17) Diagnostic delay in months (median, IQR) 10.0 (5.5–11.5) (n = 13) 57.5 (14.0–83.0) (n = 6) 21.5 (5.8–38.8) (n = 4) 12.0 (4.8–39.3) (n = 23) Survival in months (median) 22.0 (n = 22) 198.0 (n = 10) 87.0 (n = 6) 248.0 (n = 38) Versus R116G (HR, 95% CI) (0.13, 0.05–0.35) (0.24, 0.09–0.65) (0.43, 0.20–0.96) Versus D91A (HR, 95% CI) (7.71, 2.89–20.58) (9.10, 0.34–239.5) (2.19, 0.73–6.62) Versus L145F (HR, 95% CI) (4.25, 1.55–11.67) (0.11, 0.00–2.92) (1.14, 0.29–4.57) Versus others (HR, 95% CI) (2.30, 1.04–5.12) (0.46, 0.15–1.38) (0.88, 0.22–3.50) Upper motor neuron (UMN) 0.0% (n = 0) 20.0% (n = 1) 0.0% (n = 0) 6.3% (n = 1) Lower motor neuron (LMN) 14.3% (n = 1) 20.0% (n = 1) 66.6% (n = 2) 62.5% (n = 10) Classical ALS (UMN and LMN) 85.7% (n = 6) 60.0% (n = 3) 33.3% (n = 1) 31.3% (n = 5) ALSFRS-R ALS Functional Rating Scale-Revised, BMI body mass index Clinical features of ALS patients with homozygous and heterozygous SOD1 D91A genotypes Homozygous (n = 6) Heterozygous (n = 4) Age of onset (mean, SD) 53.2 (± 12.7) (n = 6) 46.8 (± 15.5) (n = 4) Male 50.0% (n = 3) 25.0% (n = 1) Female 50.0% (n = 3) 75.0% (n = 3) Spinal 100.0% (n = 3) 100.0% (n = 3) Bulbar 0.0% (n = 0) 0.0% (n = 0) Positive 66.7% (n = 4) 25.0% (n = 1) Negative 33.3% (n = 2) 75.0% (n = 3) ALSFRS-R (1st visit) (median, IQR) 41.0 (38.0–44.0) (n = 4) 35.0 (27.0–37.0) (n = 4) Progression rate (median, IQR) (onset to last visit) 0.17 (0.07–0.33) (n = 4) 0.11 (0.08–0.46) (n = 4) BMI in kg/m2 (mean, SD) 23.0 (± 2.4) (n = 2) 25.2 (± 5.3) (n = 4) Diagnostic delay in months (mean, SD) 35.0 (± 31.2) (n = 3) 78.0 (± 17.0) (n = 3) ALSFRS-R ALS Functional Rating Scale-Revised, BMI body mass index Figure 1 which previously appeared as (Figure presented.) Fig. 1 Clinical characteristics in R116G carriers vs. D91A carriers (homozygous and heterozygous) vs. L145F carriers. Boxplots show median (IQR; minimum–maximum). (a) age of onset (b) progression rate (c) diagnostic delay (d) ALSFRS-R at first visit. Experimental units n = number (a) R116G n = 22, D91A n = 10, p = 0.6814, R116G n = 22, L145F n = 6, p = 0.9239, D91A n = 10, L144F n = 6, p = 0.9798 (b) R116G n = 14, D91A n = 8, p = 0.0183, R116G n = 14, L145F n = 6, p = 0.2125, D91A n = 8, L145F n = 6, p = 0.3526 (c) R116G n = 13, D91A n = 6, p = 0.0008, R116G n = 13, L145F n = 4, p = 0.2723, D91A n = 6, L145F n = 4, p = 0.1286 (d) R116G n = 14, D91A n = 8, p = 0.0439, R116G n = 14, L145F n = 6, p = 0.08256, D91A n = 8, L145F n = 6, p = 0.4336. Mann–Whitney U test was used for two group comparison. A P-value of ≤ 0.05 was regarded as statistically significant. ALSFRS-R Amyotrophic lateral sclerosis functional rating scale revised Figure 1 should have appeared as shown below (Figure presented.) Clinical characteristics in R116G carriers vs. D91A carriers (homozygous and heterozygous) vs. L145F carriers. Boxplots show median (IQR; minimum–maximum). (a) Age of onset, (b) progression rate, (c) diagnostic delay, (d) ALSFRS-R at first visit. Experimental units n = number (a) R116G n = 22, D91A n = 10, p = 0.6814, R116G n = 22, L145F n = 6, p = 0.9239, D91A n = 10, L144F n = 6, p = 0.9798; (b) R116G n = 14, D91A n = 8, p = 0.0159, R116G n = 14, L145F n = 6, p = 0.2391, D91A n = 8, L145F n = 6, p = 0.2824; c R116G n = 13, D91A n = 6, p = 0.0008, R116G n = 13, L145F n = 4, p = 0.2723, D91A n = 6, L145F n = 4, p = 0.1286; (d) R116G n = 14, D91A n = 8, p = 0.0439, R116G n = 14, L145F n = 6, p = 0.08256, D91A n = 8, L145F n = 6, p = 0.4336. Mann–Whitney U test was used for two group comparison. A P-value of ≤ 0.05 was regarded as statistically significant. ALSFRS-R amyotrophic lateral sclerosis Functional Rating Scale Revised
CRIS-Team Scopus Importer:2025-04-01

Correction to: Development and clinical validation of inertial sensor-based gait-clustering methods in Parkinson's disease (J Neuroeng Rehabil (2019) 16:77 DOI: 10.1186/s12984-019-0548-2) - Nguyen, An; Roth, Nils; Haji Ghassemi, Nooshin; Hannink, Julius; Seel, Thomas; Klucken, Jochen; Gaßner, Heiko; Eskofier, Björn (Journal of neuroEngineering and rehabilitation, 2019)
The original article [1] contained an error whereby Fig. 6 contained a minor shading glitch affecting its presentation. This has now been corrected.
CRIS-Team Scopus Importer:2019-08-06

Correction to: Erectile Dysfunction - Hilz, Max-Josef; Wang, Ruihao; Vodušek, David B. (Springer International Publishing, 2023)
CRIS-Team Scopus Importer:2024-12-16

Correction to: Expression of Inflammatory Mediators in Biofilm Samples and Clinical Association in Multiple Sclerosis Patients in Remission—A Pilot Study (Life, (2024), 14, 3, (367), 10.3390/life14030367) - Fehlhofer, Jakob Paul; Ries, Jutta; Nickel, Florian; Rothhammer, Veit; Schwab, Stefan; Kesting, Marco Rainer; Buchbender, Mayte (Life, 2024)
The reference 22 was deleted in the original publication [1]. With this correction, the order of some references has been adjusted accordingly. The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated.
CRIS-Team Scopus Importer:2024-09-06

Correction to: Gait variability as digital biomarker of disease severity in Huntington’s disease (Journal of Neurology, (2020), 10.1007/s00415-020-09725-3) - Gaßner, Heiko; Jensen, Dennis; Marxreiter, Franz; Kletsch, Anja; Bohlen, Stefan; Schubert, Robin; Muratori, Lisa M.; Eskofier, Björn; Klucken, Jochen; Winkler, Jürgen; Reilmann, Ralf; Kohl, Zacharias (Journal of Neurology, 2020)
The original version of this article unfortunately contained a mistake. The name of one author is not presented correctly in the author group. The correct name should be Franz Marxreiter.
CRIS-Team Scopus Importer:2020-04-03

Correction to: Ganglioglioma with adverse clinical outcome and atypical histopathological features were defined by alterations in PTPN11/KRAS/NF1 and other RAS-/MAP-Kinase pathway genes (Acta Neuropathologica, (2023), 10.1007/s00401-023-02561-5) - Hoffmann, Lucas; Coras, Roland; Kobow, Katja; López-Rivera, Javier A.; Lal, Dennis; Leu, Costin; Najm, Imad; Nürnberg, Peter; Herms, Jochen; Harter, Patrick N.; Bien, Christian G.; Kalbhenn, Thilo; et al. (Acta Neuropathologica, 2023)
In the original publication, incorrect version of Fig. 3 and wrong format of Table 1 were published. Specifically, the labels in Fig. 3 were missing and columns of Table 1 were not in the right format. The correct versions of Fig. 3 and Table 1 are shown below. The original article has been corrected.
CRIS-Team Scopus Importer:2023-05-05

Correction to: Gap Analysis Regarding Prognostication in Neurocritical Care: A Joint Statement from the German Neurocritical Care Society and the Neurocritical Care Society - Wartenberg, Katja E.; Hwang, David Y.; Haeusler, Karl Georg; Muehlschlegel, Susanne; Sakowitz, Oliver W.; Madžar, Dominik; Hamer, Hajo; Rabinstein, Alejandro A.; Greer, David M.; Hemphill, J. Claude; Meixensberger, Juergen; Varelas, Panayiotis N. (Neurocritical Care, 2019)
This article was updated to correct the spelling of Karl Georg Haeusler.
CRIS-Team Scopus Importer:2019-08-30

Correction to: Neck cooling induces blood pressure increase and peripheral vasoconstriction in healthy persons (Neurological Sciences, (2020), 41, 9, (2521-2529), 10.1007/s10072-020-04349-x) - Köhn, Julia; Wang, Ruihao; de Rojas Leal, Carmen; Kallmünzer, Bernd; Winder, Klemens; Köhrmann, Martin; Kollmar, Rainer; Schwab, Stefan; Hilz, Max-Josef (Neurological Sciences, 2021)
The article “Neck cooling induces blood pressure increase and peripheral vasoconstriction in healthy persons”, written by Julia Koehn, Ruihao Wang, Carmen de Rojas Leal, Bernd Kallmünzer, Klemens Winder, Martin Köhrmann, Rainer Kollmar, Stefan Schwab and Max J. Hilz, was originally published Online First without Open Access. After publication in volume 41, issue 9, page 2521–2529 the authors decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to © The Author(s) 2020 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4.0. The original article has been corrected.
CRIS-Team Scopus Importer:2021-07-16

Correction to: Routine diagnostics for neural antibodies, clinical correlates, treatment and functional outcome (Journal of Neurology, (2020), 10.1007/s00415-020-09814-3) - Bien, Christian G.; Bien, Corinna I.; Dogan Onugoren, Müjgan; De Simoni, Desiree; Eigler, Verena; Haensch, Carl Albrecht; Holtkamp, Martin; Ismail, Fatme S.; Kurthen, Martin; Melzer, Nico; Mayer, Kristina; von Podewils, Felix; et al. (Journal of Neurology, 2020)
The original version of this article unfortunately contained a mistake.
CRIS-Team Scopus Importer:2020-05-22

Correction to: Routine diagnostics for neural antibodies, clinical correlates, treatment and functional outcome (Journal of Neurology, (2020), 267, 7, (2101-2114), 10.1007/s00415-020-09814-3) - Bien, Christian G.; Bien, Corinna I.; Onugoren, Mujgan Dogan; De Simoni, Desiree; Eigler, Verena; Haensch, Carl-Albrecht; Holtkamp, Martin; Ismail, Fatme S.; Kurthen, Martin; Melzer, Nico; Mayer, Kristina; Von Podewils, Felix; et al. (Journal of Neurology, 2021)
The article Routine diagnostics for neural antibodies, clinical correlates, treatment and functional outcome, written by Christian G. Bien, Corinna I. Bien, Müjgan Dogan Onugoren, Desiree De Simoni, Verena Eigler, Carl-Albrecht Haensch, Martin Holtkamp, Fatme S. Ismail, Martin Kurthen, Nico Melzer, Kristina Mayer, Felix von Podewils, Helmut Rauschka, Andrea O. Rossetti, Wolf-Rudiger Schäbitz, Olga Simova, Karsten Witt, Romana Höftberger and Theodor W. May, was originally published Online First without Open Access. After publication in volume 267, issue 7, page 2101–2114 the author decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to © The Author(s) 2021 and this article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Open Access funding enabled and organized by Projekt DEAL. The original article has been corrected.
CRIS-Team Scopus Importer:2021-07-23

Correction to: Telemedicine in general neurology: use of audiovisual consultation for on call back-up service in an acute care hospital - Janssen, Frank; Awadallah, Mohammed; Alhalabi, Awed; Koerber, Barbara; Lang, Reinhard; Scibor, Mateusz; Handschu, Rene (Journal of Neurology, 2019)
The original version of this article unfortunately contained a mistake in the acknowledgement section.
EVALuna2:206748

Correlation between clinical severity and extent of autonomic cardiovascular impairment in the acute phase of subarachnoid hemorrhage - Borutta, Matthias; Gerner, Stefan T.; Möser, Philip; Hölter, Philip; Engelhorn, Tobias; Dörfler, Arnd; Huttner, Hagen B.; Schwab, Stefan; Kuramatsu, Joji; Köhn, Julia (Journal of Neurology, 2022)
Background and aim: To assess associations between clinical severity and possible dysfunction of autonomic cardiovascular modulation within the acute phase after spontaneous subarachnoid hemorrhage (SAH). Methods: In this prospective observational study, in 51 patients with spontaneous SAH, Hunt-and-Hess scores (H&H) were assessed and cardiovascular autonomic modulation was monitored within 24 h after SAH-onset. From 5 min time-series of R–R-intervals (RRI) and blood-pressure (BP) recordings, we calculated autonomic parameters including time-domain [RRI-coefficient-of-variation (RRI-CV) and square-root-of-the-mean-squared-differences-of-successive-RRIs (RMSSD)] and frequency-domain parameters [low- and high-frequency-powers of RRI- and BP-modulation (RRI-LF-, RRI-HF-, SBP-LF-powers) and RRI-total-powers]. Data were compared to those of 20 healthy volunteers. Results: RRI- and BP-values did not differ between groups. Yet, parameters of sympathetic (RRI-LF-powers 141.0 (18.9–402.4) ms2 vs 442.3 (246.8–921.2) ms2, p = 0.001) and total autonomic modulation (RRI-CV 2.4 (1.2–3.7) ms2 vs 3.7 (3.1–5.3) ms2, p = 0.001) were significantly lower in patients than in controls. Subgroup analyses (patients with H&H < 3 vs H&H ≥ 3) and Spearman-rank-correlations revealed increasing loss of sympathetic (RRI-LF-powers 338.6 (179.7–710.4) ms2 vs 72.1 (10.1–175.9) ms2, p = 0.001, rho = − 0.524) and total autonomic modulation (RRI-CV 3.5 (2.3–5.4) ms2 vs 1.6 (1.0–2.8) ms2, p < 0.001, rho = − 0.519) with higher H&H-scores. Multiple-logistic-regression underlined the significant influence of H&H-scores on sympathetic (RRI-LF-powers, p = 0.033) and total autonomic modulation (RRI-CV, p = 0.040) compared to possible confounders (e.g., age, intubation). Conclusion: Within the acute phase, spontaneous SAH induces a decrease in sympathetic and total autonomic cardiovascular modulation. Higher H&H-scores were associated with increasing autonomic dysfunction and may therefore augment the risk of cardiovascular complications and poor clinical outcome.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Autonomic nervous system; Heart rate variability; Hunt and Hess; Subarachnoid hemorrhage

Corrigendum: Cathepsin D Variants Associated With Neurodegenerative Diseases Show Dysregulated Functionality and Modified α-Synuclein Degradation Properties (Frontiers in Cell and Developmental Biology, (2021), 9, (581805), 10.3389/fcell.2021.581805) - Bunk, Josina; Prieto Huarcaya, Susy; Drobny, Alice; Dobert, Jan; Walther, Lina; Rose-John, Stefan; Arnold, Philipp; Zunke, Friederike (Frontiers in Cell and Developmental Biology, 2021)
In the original article, there was a mistake in Figure 1C as published. In the Coomassie brilliant blue (CBB) protein staining, which was used as additional loading control (besides GAPDH), 11 instead of 10 sample lanes (+ protein ladder) were shown in the original Figure 1C. This mistake resulted from an additional sample (transfection control), that was loaded on the far right. This lane was not shown in both immunoblots (CTSD and GAPDH), but accidentally was still shown in the CBB control. The corrected Figure 1C appears below. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. (Figure presented.).
CRIS-Team Scopus Importer:2021-07-16
Keywords: alpha-synuclein; cathepsin D; lysosomal degradation; lysosomes; molecular dynamics simulation; neuronal ceroid lipofuscinoses; Parkinson's disease

Corrigendum: “Electrodiagnostic assessment of the autonomic nervous system: A consensus statement endorsed by the American Autonomic Society, American Academy of Neurology, and the International Federation of Clinical Neurophysiology” (Clinical Neurophysiology (2021) 132(2) (666–682), (S138824572030585X), (10.1016/j.clinph.2020.11.024)) - Cheshire, William P.; Freeman, Roy; Gibbons, Christopher H.; Cortelli, Pietro; Wenning, Gregor K.; Hilz, Max-Josef; Spies, Judith M.; Lipp, Axel; Sandroni, Paola; Wada, Naoki; Mano, Tadaaki; Kim, Hyun Ah; et al. (Clinical Neurophysiology, 2021)
The authors would like to inform you that the name of the 11th author, Tadaaki Mano, was incorrectly stated as Akiko Mano in their published article. The correct details updated as above. The authors apologise for this error.
CRIS-Team Scopus Importer:2021-03-26

Corrigendum: Feasibility and Diagnostic Accuracy of Ischemic Stroke Territory Recognition Based on Two-dimensional Projections of Three-dimensional Diffusion MRI Data - Wrosch, Jana Katharina; Volbers, Bastian; Gölitz, Philipp; Gilbert, Daniel; Schwab, Stefan; Dörfler, Arnd; Kornhuber, Johannes; Groemer, Teja Wolfgang (Frontiers in Neurology, 2017)
[This corrects the article on p. 239 in vol. 6, PMID: 26635717.].
EVALuna2:22534

Corrigendum to “Fluoxetine ameliorates behavioral and neuropathological deficits in a transgenic model mouse of α-synucleinopathy” Exp Neurol. 2012 April; 234(2): 405–416 (Fluoxetine ameliorates behavioral and neuropathological deficits in a transgenic model mouse of α-synucleinopathy (2012) 234(2) (405–416), (S001448861200009X), (10.1016/j.expneurol.2012.01.008)) - Ubhi, Kiren; Inglis, Chandra; Mante, Michael; Patrick, Christina; Adame, Anthony; Spencer, Brian; Rockenstein, Edward; May, Verena Elisabeth Luise; Winkler, Juergen; Masliah, Eliezer (Experimental Neurology, 2024)
The authors regret that during the process of assembling the panels for Fig. 4 and error occurred where the incorrect panel was used to represent the the non transgenic saline PCNA condition in Fig. 4F. The corrected Fig. 4 including panel 4F is provided below. We apologize for any inconvenience caused, and have confirmed that the conclusions were not affected.[Formula presented]
CRIS-Team Scopus Importer:2024-07-19

Corrigendum to “RIP1-RIP3-DRP1 pathway regulates NLRP3 inflammasome activation following subarachnoid hemorrhage”. Experimental Neurology. 2017 Sep: 295:116–124. (Experimental Neurology (2017) 295 (116–124), (S0014488617301425), (10.1016/j.expneurol.2017.06.003)) - Zhou, Keren; Shi, Ligen; ZhenWang,; Zhou, Jingyi; Manaenko, Anatol; Reis, Cesar; Chen, Sheng; Zhang, Jianmin (Experimental Neurology, 2024)
The authors regret that the picture in Fig. 6C was mistakenly picked in the article as originally published. The authors show the correct picture in the newly provided Fig. 6. This change will not have any effect on the results of the study.[Formula presented] The authors would like to apologise for any inconvenience caused.
CRIS-Team Scopus Importer:2024-05-03

Corticosteroids in patients with vestibular neuritis: An updated meta-analysis - Bogdanova, Anna; Dlugaiczyk, Julia; Heckmann, Josef Georg; Schwab, Stefan (Acta Neurologica Scandinavica, 2022)
Vestibular neuritis is a common neuro-otological entity. Therapeutically, corticosteroids are advised, although the evidence is limited. The objective of this review is to update meta-analyses of clinical trials that address the question of whether patients with vestibular neuritis treated with corticosteroids show better recovery than control patients. The electronic databases Medline, Scopus and Cochrane were searched for clinical trials for the years 1970-2020 without language restriction. Data were extracted, and outcome parameters were subjected to conventional and cumulative meta-analysis using a commercially available software program (). Finally, 15 trials with 363 participants in the treatment and 489 in the control groups were identified and could be included. Eight studies were judged to be at high risk of bias. The odds ratio (OR) for good outcome in the acute phase was 3.1 (95% CI 1.2-7.8; p = .015) in favour of steroid treatment leading to the number needed to treat (NNT) = 6 (95% CI 4-23). The odds ratio (OR) for restoration of vestibular function in the follow-up was 2.4 (95% CI 1.3-4.4; p = .004) for the benefit of steroid treatment resulting in a NNT = 7 (95% CI 5-18). The results of the cumulative statistics did not differ. The risk of adverse effects was higher in patients treated with steroids with an OR of 10.9 (95% CI 1.3-93.8; p = .015) and an estimated number needed to harm (NNH) = 4 (95% CI 3-19). The advantage for corticosteroids remained when differentiating between patients who participated in randomized or non-randomized clinical trials. Steroid treatment in vestibular neuritis resulted in a statistically significant benefit compared to control therapies. However, broad heterogeneity of the studies, mostly low-grade quality of studies, high risk of bias and broad confidence intervals put the findings into perspective allowing only a careful judgement of some benefit of corticosteroids. The findings, however, support the call for an adequately powered and well-designed randomized controlled trial to re-evaluate the effectiveness of corticosteroids.
CRIS-Team WoS Importer:2022-09-09

Costs of epilepsy and cost-driving factors in children, adolescents, and their caregivers in Germany - Riechmann, Janna; Strzelczyk, Adam; Reese, Jens P.; Boor, Rainer; Stephani, Ulrich; Langner, Cornelia; Neubauer, Bernd A.; Oberman, Bettina; Philippi, Heike; Rochel, Michael; Seeger, Juergen; Seipelt, Peter; et al. (Epilepsia, 2015)
To provide first data on the cost of epilepsy and cost-driving factors in children, adolescents, and their caregivers in Germany.A population-based, cross-sectional sample of consecutive children and adolescents with epilepsy was evaluated in the states of Hessen and Schleswig-Holstein (total of 8.796 million inhabitants) in all health care sectors in 2011. Data on socioeconomic status, course of epilepsy, and direct and indirect costs were recorded using patient questionnaires.We collected data from 489 children and adolescents (mean age ± SD 10.4 ± 4.2 years, range 0.5-17.8 years; 264 [54.0%] male) who were treated by neuropediatricians (n = 253; 51.7%), at centers for social pediatrics ("Sozialpaediatrische Zentren," n = 110, 22.5%) and epilepsy centers (n = 126; 25.8%). Total direct costs summed up to EUR1,619 ± EUR4,375 per participant and 3-month period. Direct medical costs were due mainly to hospitalization (47.8%, EUR774 ± EUR3,595 per 3 months), anticonvulsants (13.2%, EUR213 ± EUR363), and ancillary treatment (9.1%, EUR147 ± EUR344). The total indirect costs amounted to EUR1,231 ± EUR2,830 in mothers and to EUR83 ± EUR593 in fathers; 17.4% (n = 85) of mothers and 0.6% (n = 3) of fathers reduced their working hours or quit work because of their child's epilepsy. Independent cost-driving factors were younger age, symptomatic cause, and polytherapy with anticonvulsants. Older age, active epilepsy, symptomatic cause, and polytherapy were independent predictors of higher antiepileptic drug (AED) costs, whereas younger age, longer epilepsy duration, symptomatic cause, disability, and parental depression were independent predictors for higher indirect costs.Treatment of children and adolescents with epilepsy is associated with high direct costs due to frequent inpatient admissions and high indirect costs due to productivity losses in mothers. Direct costs are age-dependent and higher in patients with symptomatic epilepsy and polytherapy. Indirect costs are higher in the presence of a child's disability and parental depression.
EVALuna2:22370

Could the 2017 ILAE and the four-dimensional epilepsy classifications be merged to a new “Integrated Epilepsy Classification”? - Rosenow, Felix; Akamatsu, Naoki; Bast, Thomas; Bauer, Sebastian; Baumgartner, Christoph; Benbadis, Selim; Bermeo-Ovalle, Adriana; Beyenburg, Stefan; Bleasel, Andrew; Bozorgi, Alireza; Brázdil, Milan; Carreño, Mar; et al. (Seizure-European Journal of Epilepsy, 2020)
Over the last few decades the ILAE classifications for seizures and epilepsies (ILAE-EC) have been updated repeatedly to reflect the substantial progress that has been made in diagnosis and understanding of the etiology of epilepsies and seizures and to correct some of the shortcomings of the terminology used by the original taxonomy from the 1980s. However, these proposals have not been universally accepted or used in routine clinical practice. During the same period, a separate classification known as the “Four-dimensional epilepsy classification” (4D-EC) was developed which includes a seizure classification based exclusively on ictal symptomatology, which has been tested and adapted over the years. The extensive arguments for and against these two classification systems made in the past have mainly focused on the shortcomings of each system, presuming that they are incompatible. As a further more detailed discussion of the differences seemed relatively unproductive, we here review and assess the concordance between these two approaches that has evolved over time, to consider whether a classification incorporating the best aspects of the two approaches is feasible. To facilitate further discussion in this direction we outline a concrete proposal showing how such a compromise could be accomplished, the “Integrated Epilepsy Classification”. This consists of five categories derived to different degrees from both of the classification systems: 1) a “Headline” summarizing localization and etiology for the less specialized users, 2) “Seizure type(s)”, 3) “Epilepsy type” (focal, generalized or unknown allowing to add the epilepsy syndrome if available), 4) “Etiology”, and 5) “Comorbidities & patient preferences”.
CRIS-Team Scopus Importer:2020-03-17
Keywords: 2017 ILAE classification; Classification; Classification merger; Epilepsy classification; Four-dimensional epilepsy; Integrated epilepsy classsifcation; Semiological seizure classification

Critique of the 2017 epileptic seizure and epilepsy classifications - Lüders, Hans; Akamatsu, Naoki; Amina, Shahram; Baumgartner, Christoph; Benbadis, Selim; Bermeo-Ovalle, Adriana; Bleasel, Andrew; Bozorgi, Alireza; Carreño, Mar; Devereaux, Michael; Fernandez-Baca Vaca, Guadalupe; Francione, Stefano; et al. (Epilepsia, 2019)
This article critiques the International League Against Epilepsy (ILAE) 2015-2017 classifications of epilepsy, epileptic seizures, and status epilepticus. It points out the following shortcomings of the ILAE classifications: (1) they mix semiological terms with epileptogenic zone terminology; (2) simple and widely accepted terminology has been replaced by complex terminology containing less information; (3) seizure evolution cannot be described in any detail; (4) in the four-level epilepsy classification, level two (epilepsy category) overlaps almost 100% with diagnostic level one (seizure type); and (5) the design of different classifications with distinct frameworks for newborns, adults, and patients in status epilepticus is confusing. The authors stress the importance of validating the new ILAE classifications and feel that the decision of Epilepsia to accept only manuscripts that use the ILAE classifications is premature and regrettable.
CRIS-Team Scopus Importer:2019-05-07
Keywords: classification; epileptogenic zone; etiology; semiology

Cryo-TEM structure of β-glucocerebrosidase in complex with its transporter LIMP-2 - Dobert, Jan; Schäfer, Jan-Hannes; Dal Maso, Thomas; Ravindran, Priyadarshini; Huard, Dustin J. E.; Socher, Eileen; Schildmeyer, Lisa A.; Lieberman, Raquel L.; Versées, Wim; Moeller, Arne; Zunke, Friederike; Arnold, Philipp (Nature Communications, 2025)
Targeting proteins to their final cellular destination requires transport mechanisms and nearly all lysosomal enzymes reach the lysosome via the mannose-6-phosphate receptor pathway. One of the few known exceptions is the enzyme β-glucocerebrosidase (GCase) that requires the lysosomal integral membrane protein type-2 (LIMP-2) as a proprietary lysosomal transporter. Genetic variations in the GCase encoding gene GBA1 cause Gaucher’s disease (GD) and present the highest genetic risk factor to develop Parkinson’s disease (PD). Activators targeting GCase emerge as a promising therapeutic approach to treat GD and PD, with pre-clinical and clinical trials ongoing. In this study, we resolve the complex of GCase and LIMP-2 using cryo-electron microscopy with the aid of an engineered LIMP-2 shuttle and two GCase-targeted pro-macrobodies. We identify helix 5 and helix 7 of LIMP-2 to interact with a binding pocket in GCase, forming a mostly hydrophobic interaction interface supported by one essential salt bridge. Understanding the interplay of GCase and LIMP-2 on a structural level is crucial to identify potential activation sites and conceptualizing novel therapeutic approaches targeting GCase. Here, we unveil the protein structure of a mannose-6-phosphate-independent lysosomal transport complex and provide fundamental knowledge for translational clinical research to overcome GD and P
Keywords: Cryoelectron microscopy; Enzymes; Membrane proteins; Parkinson's disease

CSF1R-Mediated Myeloid Cell Depletion Prolongs Lifespan But Aggravates Distinct Motor Symptoms in a Model of Multiple System Atrophy - Battis, Kristina; Florio, Jazmin B.; Mante, Michael; Lana, Addison; Naumann, Isabel; Gauer, Carina; Lambrecht, Vera; Müller, Sarina Katrin; Cobo, Isidoro; Fixsen, Bethany; Kim, Ha Yeon; Masliah, Eliezer; et al. (Journal of Neuroscience, 2022)
As the CNS-resident macrophages and member of the myeloid lineage, microglia fulfill manifold functions important for brain development and homeostasis. In the context of neurodegenerative diseases, they have been implicated in degenerative and regenerative processes. The discovery of distinct activation patterns, including increased phagocytosis, indicated a damaging role of myeloid cells in multiple system atrophy (MSA), a devastating, rapidly progressing atypical parkinsonian disorder. Here, we analyzed the gene expression profile of microglia in a mouse model of MSA (MBP29-ha-syn) and identified a disease-associated expression profile and upregulation of the colony-stimulating factor 1 (Csf1). Thus, we hypothesized that CSF1 receptor-mediated depletion of myeloid cells using PLX5622 modifies the disease progression and neuropathological phenotype in this mouse model. Intriguingly, sex-balanced analysis of myeloid cell depletion in MBP29-ha-syn mice revealed a two-faced outcome comprising an improved survival rate accompanied by a delayed onset of neurological symptoms in contrast to severely impaired motor functions. Furthermore, PLX5622 reversed gene expression profiles related to myeloid cell activation but reduced gene expression associated with transsynaptic signaling and signal release. While transcriptional changes were accompanied by a reduction of dopaminergic neurons in the SNpc, striatal neuritic density was increased upon myeloid cell depletion in MBP29-ha-syn mice. Together, our findings provide insight into the complex, two-faced role of myeloid cells in the context of MSA emphasizing the importance to carefully balance the beneficial and adverse effects of CSF1R inhibition in different models of neurodegenerative disorders before its clinical translation.
CRIS-Team Scopus Importer:2022-11-04
Keywords: colony-stimulating factor 1 receptor; motor function; multiple system atrophy; myeloid cells; neuron-micro-glia interaction; PLX5622

CSF1R-mediated myeloid cell depletion shifts the ratio of motor cortical excitatory to inhibitory neurons in a multiple system atrophy model - Gauer, Carina; Battis, Kristina; Schneider, Yanni; Florio, J. B.; Mante, M.; Kim, H. Y.; Rissman, R. A.; Hoffmann, Alana; Winkler, Jürgen (Experimental Neurology, 2024)
Motor cortical circuit functions depend on the coordinated fine-tuning of two functionally diverse neuronal populations: glutamatergic pyramidal neurons providing synaptic excitation and GABAergic interneurons adjusting the response of pyramidal neurons through synaptic inhibition. Microglia are brain resident macrophages which dynamically refine cortical circuits by monitoring perineuronal extracellular matrix and remodelling synapses. Previously, we showed that colony-stimulating factor 1 receptor (CSF1R)-mediated myeloid cell depletion extended the lifespan, but impaired motor functions of MBP29 mice, a mouse model for multiple system atrophy. In order to better understand the mechanisms underlying these motor deficits we characterized the microglial involvement in the cortical balance of GABAergic interneurons and glutamatergic pyramidal neurons in 4-months-old MBP29 mice following CSF1R inhibition for 12 weeks. Lack of myeloid cells resulted in a decreased number of COUP TF1 interacting protein 2-positive (CTIP2+) layer V pyramidal neurons, however in a proportional increase of calretinin-positive GABAergic interneurons in MBP29 mice. While myeloid cell depletion did not alter the expression of important presynaptic and postsynaptic proteins, the loss of cortical perineuronal net area was attenuated by CSF1R inhibition in MBP29 mice. These cortical changes may restrict synaptic plasticity and potentially modify parvalbumin-positive perisomatic input. Collectively, this study suggests, that the lack of myeloid cells shifts the neuronal balance toward an increased inhibitory connectivity in the motor cortex of MBP29 mice thereby potentially deteriorating motor functions.
CRIS-Team Scopus Importer:2024-03-08
Keywords: Colony-stimulating factor 1 receptor; Excitation-inhibition balance; GABAergic interneurons; Microglia-neuron-interaction; Motor cortex; Multiple system atrophy; PLX5622; Pyramidal neurons

CT-derived left ventricular global strain: a head-to-head comparison with speckle tracking echocardiography - Ammon, Fabian; Bittner, D.; Hell, M.; Mansour, H.; Achenbach, Stephan; Marwan, Mohamed; Arnold, Martin (International Journal of Cardiovascular Imaging, 2019)
We assessed CT-derived left ventricular strain in a cohort of patients referred for transcatheter aortic valve implantation (TAVI) and validated it against 2 dimensional speckle tracking echocardiography as the gold standard. 65 consecutive patients with symptomatic aortic valve stenosis referred for CT imaging prior to TAVI were included in this analysis. For all patients, retrospectively ECG-gated multi-phase functional CT data sets acquired with identical reconstruction parameters were available. All data sets were acquired using a third generation dual source system. In all patients, multiphase reconstructions in increments of 10% of the cardiac cycle were rendered (slice thickness 0.75, increment 0.5 mm, medium smooth reconstruction kernel) and transferred to a dedicated workstation (Ziostation2, Ziosoft Inc., Tokyo, Japan). Additional functional reconstructions for dynamic assessment and quantification of strain were processed. Multiplanar reconstructions (MPR) of the left ventricle similar to standard echocardiographic 4, 2 and apical 3 chamber views were rendered in CT. Similar to echocardiographic longitudinal strain, the perimeter of the left ventricle was manually traced within the myocardium and peak maximal shortening as a parameter representing longitudinal strain was calculated for each view and averaged to obtain a marker for global longitudinal strain (CT perimeter-derived strain). Furthermore, for quantification of 3-dimensional strain, endocardial and epicardial borders of myocardium were marked in six short axis views and peak maximum 3- dimensional strain of the myocardium was calculated in standard six basal, six mid and four apical segments. 3-dimensional strain values of the 16 standard segments as well as perimeter-derived strain values in the three standard windows were averaged to obtain global strain. Echocardiography was performed in all patients before CT data acquisition. Digital loops were acquired from three apical views (four-, two-, and three chamber views). For assessment of 2 dimensional global longitudinal strain (GLS), recordings were processed with acoustic-tracking software allowing offline semiautomated speckle-based strain analyses. The mean age of all 65 patients was 81 ± 5 years. The mean echocardiographic ejection fraction and mean echocardiographic GLS were 50 ± 12% and −13.6 ± 4.5%, respectively. The mean CT-derived peak 3-dimensional global strain and mean peak strain derived by perimeter was 43.2 ± 13.5% and −11.2 ± 3.5%, respectively. Both CTderived global 3D-strain and perimeter derived strain showed a significant correlation to GLS derived by echocardiography (r = −0.8, p < 0.0001 for 3D strain and r = 0.71, p < 0.0001 for perimeter-derived strain). Bland-Altman analysis showed a systematic underestimation (i. e. worse strain values) of CT perimeter-derived strain compared to GLS by echocardiography (mean difference −2.4% with 95% limits of agreement between 4% to −9%). ROC Curve analysis assuming a normal GLS when less than −18% showed that a CT-derived peak 3-dimensional global strain cut-off-value of 45% has a sensitivity of 91% and a specificity of 60% for detecting normal left ventricular strain (AUC 0.81, p = 0.001). For CT perimeter-derived strain, a cut-off value of −12%—assuming a normal echocardiographic GLS when less than −18%—achieved a sensitivity of 82% and a specificity of 61% (AUC of 0.82, p = 0.001) for detecting abnormal left ventricular strain. Using dedicated software, assessment of CT-derived left ventricular strain is feasible and comparable to strain derived by echocardiographic 2 dimensional speckle tracking.
CRIS-Team Scopus Importer:2019-05-07
Keywords: Cardiac CT angiography; Echocardiography; Left ventricular global strain; Speckle tracking

CT-derived left ventricular global strain in aortic stenosis patients referred for transcatheter aortic valve implantation: a head-to-head comparison with echocardiography - Ammon, Fabian; Bittner, D.; Hell, M.; Schuhbaeck, A.; Röther, Jens; Feyrer, R.; Achenbach, Stephan; Marwan, Mohamed; Arnold, Martin (EUROPEAN HEART JOURNAL, 2018)
CRIS-Team WoS Importer:2019-03-15

CT-derived left ventricular global strain in aortic valve stenosis patients: A comparative analysis pre and post transcatheter aortic valve implantation - Ammon, Fabian; Bittner, D.; Röther, Jens; Mekkhala, N.; Hell, M.; Schuhbaeck, A.; Gitsioudis, Gitsios; Feyrer, R.; Schlundt, Christian; Achenbach, Stephan; Marwan, Mohamed; Arnold, Martin (Journal of Cardiovascular Computed Tomography, 2018)
INTRODUCTION: We assessed the potential of CT strain to detect changes in myocardial function in patients referred for TAVI pre and post intervention. PATIENTS AND METHODS: 25 consecutive patients with symptomatic aortic valve stenosis in whom TAVI had been performed were included in this analysis. Functional CT data sets acquired before and 3 to 6 months after TAVI were available. Multiphase reconstructions in increments of 10% of the cardiac cycle were rendered and transferred to a dedicated workstation (Ziostation2, Ziosoft Inc., Tokyo, Japan). For quantification of left ventricular strain, multiplanar reconstructions of the left ventricle in standard 4 chamber, 2 chamber as well as apical 3 chamber views were rendered. The perimeter of the left ventricle was traced dynamically through the cardiac cycle. Peak strain was calculated for each patient pre and post intervention. Furthermore, for quantification of 3-dimensional maximum principal strain, 2 volumetric regions of interests (VOI) were placed per each basal, mid and apical segment of the previously mentioned MPRs and peak maximal principal strain was calculated. Maximum principal strain as well as perimeter-derived longitudinal strain values in the three standard windows were averaged to obtain global strain. RESULTS: 25 patients were included in this analysis (mean age 78 ± 9 years, 13 males). Peak global maximum principal strain was significantly higher at follow-up compared to baseline (0.46 ± 0.19 vs. 0.59 ± 0.18, respectively, p = 0.001). Similarly global longitudinal strain derived by perimeter was significantly lower - implying better contraction - compared to baseline (-8.6% ± 2.8% vs. -9.8% ± 2.6%, respectively, p = 0.006). CONCLUSION: Using dedicated software, assessment of CT derived left ventricular strain is feasible. In patients treated with transcatheter aortic valve replacement, CT-derived parameters of global myocardial strain improve onshort-term follow-up.
EVALuna2:35994

Current and historical individual data about exposure of workers in the rayon industry to carbon disulfide and their validity in calculating the cumulative dose - Göen, Thomas; Schramm, Axel; Baumeister, Thomas; Uter, Wolfgang; Drexler, Hans (International Archives of Occupational and Environmental Health, 2014)
The objective of the study was to investigate how exposure to carbon disulfide (CS2) in a rayon-manufacturing plant has changed within two decades and whether it is possible to calculate valid data for the individual cumulative exposure.The data for CS2 concentration in air and biological exposure monitoring (2-thio-1,3-thiaxolidine-4-carboxylic acid (TTCA) in urine) from two cross-sectional studies, performed in 1992 (n = 362) and 2009 (n = 212) in a German rayon-manufacturing plant, were compared to data obtained from company-internal measurements between the studies.Using the data from the cross-sectional studies and company-internal data, cumulative external exposure and the cumulative internal exposure were calculated for each worker. External and internal CS2 exposure of the employees decreased from 1992 (medians 4.0 ppm and 1.63 mgTTCA/g creatinine) to 2009 (medians 2.5 ppm and 0.86 mg/g). However, company-internal CS2 data do not show a straight trend for this period. The annual medians of the company-internal measurement of external exposure to CS2 have varied between 2.7 and 8.4 ppm, in which median values exceeded 5 ppm generally since 2000. The annual medians for the company-internal biomonitoring assessment ranged between 1.2 and 2.8 mg/g creatinine. The cumulative CS2 exposure ranged from 8.5 to 869.5 ppm years for external exposure and between 1.30 and 176.2 mg/g creatinine years for the internal exposure. Significant correlations were found between the current air pollution and the internal exposure in 2009 but also between the cumulative external and internal CS2 exposure.Current exposure data, usually collected in cross-sectional studies, rarely allow a reliable statement on the cumulative dose, because of higher exposure in the past and of fluctuating courses of exposure. On the other hand, company-internal exposure data may be affected by non-representative measurement strategies. Some verification of the reliability of cumulative exposure data may be possible by testing the correlation between cumulative exposure data of external assessment and biological monitoring.
EVALuna2:5395

Current Symptomatic and Disease-Modifying Treatments in Multiple System Atrophy - Meszaros, Lisa; Hoffmann, Alana; Wihan, Jeanette; Winkler, Jürgen (International Journal of Molecular Sciences, 2020)
Multiple system atrophy (MSA) is a rare, severe, and rapidly progressive neurodegenerative disorder categorized as an atypical parkinsonian syndrome. With a mean life expectancy of 6-9 years after diagnosis, MSA is clinically characterized by parkinsonism, cerebellar ataxia, autonomic failure, and poor l-Dopa responsiveness. Aside from limited symptomatic treatment, there is currently no disease-modifying therapy available. Consequently, distinct pharmacological targets have been explored and investigated in clinical studies based on MSA-related symptoms and pathomechanisms. Parkinsonism, cerebellar ataxia, and autonomic failure are the most important symptoms targeted by symptomatic treatments in current clinical trials. The most prominent pathological hallmark is oligodendroglial cytoplasmic inclusions containing alpha-synuclein, thus classifying MSA as synucleinopathy. Additionally, myelin and neuronal loss accompanied by micro- and astrogliosis are further distinctive features of MSA-related neuropathology present in numerous brain regions. Besides summarizing current symptomatic treatment strategies in MSA, this review critically reflects upon potential cellular targets and disease-modifying approaches for MSA such as (I) targeting α-syn pathology, (II) intervening neuroinflammation, and (III) neuronal loss. Although these single compound trials are aiming to interfere with distinct pathogenetic steps in MSA, a combined approach may be necessary to slow down the rapid progression of the oligodendroglial associated synucleinopathy.
CRIS-Team Scopus Importer:2020-06-09
Keywords: disease-modifying therapy; drug development; multiple system atrophy; parkinsonian disorders

Current treatment concepts in intracerebral hemorrhage - Huttner, Hagen; Kuramatsu, J. B. (Medizinische Klinik - Intensivmedizin und Notfallmedizin, 2017)
In recent years, various important studies investigating the management of intracerebral hemorrhage (ICH) have been published. However, these have not entered guideline recommendations yet. Therefore, essential results are summarized here and the findings are integrated into current treatment concepts.Based on a dedicated literature review and the authors' experience, up-to-date and high-quality investigations were identified.Randomized data and meta-analyses provide evidence that aggressive blood-pressure reduction (targeting a systolic blood pressure <140 mm Hg) appears safe and reduces hematoma enlargement. ICH associated with intake of vitamin K antagonists should be reversed immediately using prothrombin complex concentrates (PCC) and vitamin K, targeting at least international normalized ratio levels below 1.3. For dabigatran-related ICH, an antidote (idarucizumab) is available for reversal, but in ICH under the use of factor Xa inhibitors evidence is poor. However, reversal should be carried out using high-dosed PCC (50 IU/kg PCC). Routine hematoma evacuation surgery cannot be advocated, yet new minimally invasive strategies provide promising results. In patients with acute occlusive hydrocephalus, an external ventricular drain should be placed and utilizing intraventricular lysis appears safe, reduces mortality, and is associated with improved functional outcome. Adding lumbar drainage to this treatment strategy may reduce permanent shunt dependency. The sum of treatment measures and specialized care at high-volume centers improves outcome in patients with ICH.
EVALuna2:22561

Current value of intraoperative electrocorticography (iopECoG) - Roessler, Karl; Heynold, Elisabeth; Buchfelder, Michael; Stefan, Hermann; Hamer, Hajo (Epilepsy & Behavior, 2019)
Objective: Intraoperative electrocorticography (iopECoG) can contribute to delineate the resection borders of the anticipated epileptogenic zone in epilepsy surgery. However, it has several caveats that should be considered to avoid incorrect interpretation during intraoperative monitoring.
CRIS-Team WoS Importer:2019-04-04

Dabigatran for prevention of stroke after embolic stroke of undetermined source - Diener, Hans Christoph; Sacco, Ralph L.; Donald Easton, J.; Granger, Christopher B.; Bernstein, Richard A.; Uchiyama, Shinichiro; Kreuzer, Jörg; Cronin, Lisa; Cotton, Daniel; Grauer, Claudia; Brueckmann, Martina; Chernyatina, Marina; et al. (New England Journal of Medicine, 2019)
BACKGROUND Cryptogenic strokes constitute 20 to 30% of ischemic strokes, and most cryptogenic strokes are considered to be embolic and of undetermined source. An earlier randomized trial showed that rivaroxaban is no more effective than aspirin in preventing recurrent stroke after a presumed embolic stroke from an undetermined source. Whether dabigatran would be effective in preventing recurrent strokes after this type of stroke was unclear. METHODS We conducted a multicenter, randomized, double-blind trial of dabigatran at a dose of 150 mg or 110 mg twice daily as compared with aspirin at a dose of 100 mg once daily in patients who had had an embolic stroke of undetermined source. The primary outcome was recurrent stroke. The primary safety outcome was major bleeding. RESULTS A total of 5390 patients were enrolled at 564 sites and were randomly assigned to receive dabigatran (2695 patients) or aspirin (2695 patients). During a median follow-up of 19 months, recurrent strokes occurred in 177 patients (6.6%) in the dabigatran group (4.1% per year) and in 207 patients (7.7%) in the aspirin group (4.8% per year) (hazard ratio, 0.85; 95% confidence interval [CI], 0.69 to 1.03; P=0.10). Ischemic strokes occurred in 172 patients (4.0% per year) and 203 patients (4.7% per year), respectively (hazard ratio, 0.84; 95% CI, 0.68 to 1.03). Major bleeding occurred in 77 patients (1.7% per year) in the dabigatran group and in 64 patients (1.4% per year) in the aspirin group (hazard ratio, 1.19; 95% CI, 0.85 to 1.66). Clinically relevant nonmajor bleeding occurred in 70 patients (1.6% per year) and 41 patients (0.9% per year), respectively. CONCLUSIONS In patients with a recent history of embolic stroke of undetermined source, dabigatran was not superior to aspirin in preventing recurrent stroke. The incidence of major bleeding was not greater in the dabigatran group than in the aspirin group, but there were more clinically relevant nonmajor bleeding events in the dabigatran group.
CRIS-Team Scopus Importer:2019-05-28

Dabigatran Plasma Levels in Acute Cerebrovascular Events - Volbers, Bastian; Köhrmann, Martin; Kallmünzer, Bernd; Kurka, Natalia; Breuer, Lorenz; Ringwald, Juergen; Schwab, Stefan (Journal of Stroke and Cerebrovascular Diseases, 2016)
Oral anticoagulation with dabigatran was shown to be effective for stroke prevention in patients with nonvalvular atrial fibrillation without the need for laboratory monitoring. However, a recent publication based on data of the Randomized Evaluation of Long-Term Anticoagulation Therapy study reported that ischemic stroke and bleeding outcomes are correlated with dabigatran plasma concentration (DPC). DPC was determined at a prespecified time point and correlated with cardiovascular events at any time during follow-up. Because of the known variability of DPC, among others depending on renal function, this approach might compromise data evaluation. We report on dabigatran plasma levels in acute cerebrovascular events.Consecutive patients with acute ischemic stroke (AIS) or intracerebral hemorrhage (ICH) while taking dabigatran were retrospectively identified if admission DPC was available. DPC was determined using the diluted thrombin time (Hemoclot (HYPHEN BioMed, Neuville sur Oise, France)). Creatinine clearance (CrCl) was determined by measuring creatinine in plasma and 24-hour urine.Fifteen AIS and 4 ICH patients were included. Median DPC on admission was significantly higher in ICH patients than in AIS patients (135 ng/mL [interquartile range IQR 79-218] and 69.1 ng/mL [IQR 20.6-85.0], respectively; P = .035). Increased CrCl (values above published normal range) was correlated with lower median DPC (60 ng/mL [IQR 10-69] versus 100 ng/mL [IQR 79-157] in patients with normal CrCl, P = .01).Higher DPC was found in ICH patients than in AIS patients in temporal proximity to the event. Both decreased and increased renal functions seem to have an important influence on DPC.
EVALuna2:15996

Data-driven re-referencing of intracranial EEG based on independent component analysis (ICA) - Michelmann, Sebastian; Treder, Matthias S.; Griffiths, Benjamin; Kerren, Casper; Roux, Frederic; Wimber, Maria; Rollings, David; Sawlani, Vijay; Chelvarajah, Ramesh; Gollwitzer, Stephanie; Kreiselmeyer, Gernot; Hamer, Hajo; et al. (Journal of Neuroscience Methods, 2018)
BACKGROUND: Intracranial recordings from patients implanted with depth electrodes are a valuable source of information in neuroscience. They allow for the unique opportunity to record brain activity with high spatial and temporal resolution. A common pre-processing choice in stereotactic EEG (S-EEG) is to re-reference the data with a bipolar montage. In this, each channel is subtracted from its neighbor, to reduce commonalities between channels and isolate activity that is spatially confined. NEW METHOD: We challenge the assumption that bipolar reference effectively performs this task. To extract local activity, the distribution of the signal source of interest, interfering distant signals, and noise need to be considered. Referencing schemes with fixed coefficients can decrease the signal to noise ratio (SNR) of the data, they can lead to mislocalization of activity and consequently to misinterpretation of results. We propose to use Independent Component Analysis (ICA), to derive filter coefficients that reflect the statistical dependencies of the data at hand. RESULTS: We describe and demonstrate this on human S-EEG recordings. In a simulation with real data, we quantitatively show that ICA outperforms the bipolar referencing operation in sensitivity and importantly in specificity when revealing local time series from the superposition of neighboring channels. COMPARISON WITH EXISTING METHOD(S): We argue that ICA already performs the same task that bipolar referencing pursues, namely undoing the linear superposition of activity and will identify activity that is local. CONCLUSIONS: When investigating local sources in human S-EEG, ICA should be preferred over re-referencing the data with a bipolar montage.
EVALuna2:201937

Deep Brain Stimulation for Chronic Facial Pain: An Individual Participant Data (IPD) Meta-Analysis - Qassim, HebatAllah; Zhao, Yining; Ströbel, Armin; Regensburger, Martin; Buchfelder, Michael; Souza de Oliveira, Daniela; Del Vecchio, Alessandro; Kinfe, Thomas Mehari (Brain Sciences, 2023)
Despite available, advanced pharmacological and behavioral therapies, refractory chronic facial pain of different origins still poses a therapeutic challenge. In circumstances where there is insufficient responsiveness to pharmacological/behavioral therapies, deep brain stimulation should be considered as a potential effective treatment option. We performed an individual participant data (IPD) meta-analysis including searches on PubMed, Embase, and the Cochrane Library (2000–2022). The primary endpoint was the change in pain intensity (visual analogue scale; VAS) at a defined time-point of ≤3 months post-DBS. In addition, correlation and regression analyses were performed to identify predictive markers (age, duration of pain, frequency, amplitude, intensity, contact configuration, and the DBS target). A total of seven trials consisting of 54 screened patients met the inclusion criteria. DBS significantly reduced the pain levels after 3 months without being related to a specific DBS target, age, contact configuration, stimulation intensity, frequency, amplitude, or chronic pain duration. Adverse events were an infection or lead fracture (19%), stimulation-induced side effects (7%), and three deaths (unrelated to DBS—from cancer progression or a second stroke). Although comparable long-term data are lacking, the current published data indicate that DBS (thalamic and PVG/PAG) effectively suppresses facial pain in the short-term. However, the low-quality evidence, reporting bias, and placebo effects must be considered in future randomized-controlled DBS trials for facial pain.
CRIS-Team Scopus Importer:2023-04-07
Keywords: deep brain stimulation; efficacy; facial pain; placebo; predictive outcome measures; safety

Deep learning based decoding of single local field potential events - Schilling, Achim; Gerum, Richard; Böhm, Claudia; Rasheed, Jwan; Metzner, Claus; Maier, Andreas; Reindl, Caroline; Hamer, Hajo; Krauß, Patrick (NeuroImage, 2024)
How is information processed in the cerebral cortex? In most cases, recorded brain activity is averaged over many (stimulus) repetitions, which erases the fine-structure of the neural signal. However, the brain is obviously a single-trial processor. Thus, we here demonstrate that an unsupervised machine learning approach can be used to extract meaningful information from electro-physiological recordings on a single-trial basis. We use an auto-encoder network to reduce the dimensions of single local field potential (LFP) events to create interpretable clusters of different neural activity patterns. Strikingly, certain LFP shapes correspond to latency differences in different recording channels. Hence, LFP shapes can be used to determine the direction of information flux in the cerebral cortex. Furthermore, after clustering, we decoded the cluster centroids to reverse-engineer the underlying prototypical LFP event shapes. To evaluate our approach, we applied it to both extra-cellular neural recordings in rodents, and intra-cranial EEG recordings in humans. Finally, we find that single channel LFP event shapes during spontaneous activity sample from the realm of possible stimulus evoked event shapes. A finding which so far has only been demonstrated for multi-channel population coding.
CRIS-Team Scopus Importer:2024-07-19
Keywords: Auditory cortex; Auditory neuroscience; Auto-encoder; Deep learning; Embeddings; Intracranial EEG (iEEG); Local field potentials; Speech perception; Stereotactic EEG (sEEG)

Defects in ER-endosome contacts impact lysosome function in hereditary spastic paraplegia - Allison, Rachel; Edgar, James R.; Pearson, Guy; Rizo, Tania; Newton, Timothy; Guenther, Sven; Berner, Fiamma; Hague, Jennifer; Connell, James W.; Winkler, Jürgen; Lippincott-Schwartz, Jennifer; Beetz, Christian; et al. (The Journal of Cell Biology, 2017)
Contacts between endosomes and the endoplasmic reticulum (ER) promote endosomal tubule fission, but the mechanisms involved and consequences of tubule fission failure are incompletely understood. We found that interaction between the microtubule-severing enzyme spastin and the ESCRT protein IST1 at ER-endosome contacts drives endosomal tubule fission. Failure of fission caused defective sorting of mannose 6-phosphate receptor, with consequently disrupted lysosomal enzyme trafficking and abnormal lysosomal morphology, including in mouse primary neurons and human stem cell-derived neurons. Consistent with a role for ER-mediated endosomal tubule fission in lysosome function, similar lysosomal abnormalities were seen in cellular models lacking the WASH complex component strumpellin or the ER morphogen REEP1. Mutations in spastin, strumpellin, or REEP1 cause hereditary spastic paraplegia (HSP), a disease characterized by axonal degeneration. Our results implicate failure of the ER-endosome contact process in axonopathy and suggest that coupling of ER-mediated endosomal tubule fission to lysosome function links different classes of HSP proteins, previously considered functionally distinct, into a unifying pathway for axonal degeneration.
EVALuna2:9354

Deficits in cognitive estimation in patients with right-frontal and right-temporal lobe epilepsy Neuropsychologische Schätzdefizite bei rechtsfrontaler und rechtstemporaler Epilepsie - Schwarz, Michael; Benkowitsch, Edith; Schneider, Katrin; Walther, Katrin; Hamer, Hajo (Zeitschrift für Neuropsychologie, 2021)
Background: Previous studies revealed a right-hemispheric dominance for cognitive estimation processes. Objectives: This study explored estimation impairments in patients with focal temporal and frontal lobe epilepsies. Methods: 109 patients (right frontal, left frontal, right temporal-mesial, right temporal-neocortical, left temporal-mesial, left temporal-neocortical) and a control group with 67 subjects were included. All subjects underwent an extensive neuropsychological assessment including the Test zum kognitiven Schätzen (TKS; Brand et al., 2002). Hypothesis: It was expected that right-hemispheric lesions would be associated with impairments in cognitive estimation. Results: Patients with right-frontal and right-temporal mesial focus showed significant estimation deficits compared to the other groups. Conclusion: This study shows that the right hemisphere dominantly participates in cognitive estimation.
CRIS-Team Scopus Importer:2021-06-11
Keywords: cognitive estimation; epilepsy; frontal lobe; hippocampus; laterality; temporal lobe

Defining benchmark outcomes for mesial temporal lobe epilepsy surgery: A global multicenter analysis of 1119 cases - Drexler, Richard; Ricklefs, Franz L.; Ben-Haim, Sharona; Rada, Anna; Wörmann, Friedrich; Cloppenborg, Thomas; Bien, Christian G.; Simon, Matthias; Kalbhenn, Thilo; Colon, Albert; Rijkers, Kim; Schijns, Olaf; et al. (Epilepsia, 2024)
Objective: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE). Methods: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow-up. Patients were risk-stratified by applying outcome-relevant comorbidities, and benchmarks were calculated for low-risk (“benchmark”) cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. Results: A total of 1119 patients with a mean age (range) of 36.7 (1–74) years and a male-to-female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in-hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%–72.9% of cases per center and leaving 742 patients in the high-risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow-up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1-year follow-up) and ≥69.5% (mean follow-up of 39.0 months). Significance: This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques.
CRIS-Team Scopus Importer:2024-03-15
Keywords: benchmarking; neurosurgery; outcome; quality; seizure

Delayed action does not always require the ventral stream: a study on a patient with visual form agnosia - Hesse, Constanze; Schenk, Thomas (Cortex, 2014)
It has been suggested that while movements directed at visible targets are processed within the dorsal stream, movements executed after delay rely on the visual representations of the ventral stream (Milner & Goodale, 2006). This interpretation is supported by the observation that a patient with ventral stream damage (D.F.) has trouble performing accurate movements after a delay, but performs normally when the target is visible during movement programming. We tested D.F.'s visuomotor performance in a letter-posting task whilst varying the amount of visual feedback available. Additionally, we also varied whether D.F. received tactile feedback at the end of each trial (posting through a letter box vs posting on a screen) and whether environmental cues were available during the delay period (removing the target only vs suppressing vision completely with shutter glasses). We found that in the absence of environmental cues patient D.F. was unaffected by the introduction of delay and performed as accurately as healthy controls. However, when environmental cues and vision of the moving hand were available during and after the delay period, D.F.'s visuomotor performance was impaired. Thus, while healthy controls benefit from the availability of environmental landmarks and/or visual feedback of the moving hand, such cues seem less beneficial to D.F. Taken together our findings suggest that ventral stream damage does not always impact the ability to make delayed movements but compromises the ability to use environmental landmarks and visual feedback efficiently.
EVALuna2:22298

Demonstration of brain region-specific neuronal vulnerability in human iPSC-based model of familial Parkinson's disease - Brazdis, Razvan Marius; Alecu, Julian E.; Marsch, Daniel; Dahms, Annika; Simmnacher, Katrin; Lörentz, Sandra; Brendler, Anna; Schneider, Yanni; Marxreiter, Franz; Roybon, Laurent; Winner, Beate; Xiang, Wei; et al. (Human Molecular Genetics, 2020)
Parkinson's disease (PD) is a neurodegenerative disorder characterized by protein inclusions mostly composed of aggregated forms of α-synuclein (α-Syn) and by the progressive degeneration of midbrain dopaminergic neurons (mDANs), resulting in motor symptoms. While other brain regions also undergo pathologic changes in PD, the relevance of α-Syn aggregation for the preferential loss of mDANs in PD pathology is not completely understood yet. To elucidate the mechanisms of the brain region-specific neuronal vulnerability in PD, we modeled human PD using human-induced pluripotent stem cells (iPSCs) from familial PD cases with a duplication (Dupl) of the α-Syn gene (SNCA) locus. Human iPSCs from PD Dupl patients and a control individual were differentiated into mDANs and cortical projection neurons (CPNs). SNCA dosage increase did not influence the differentiation efficiency of mDANs and CPNs. However, elevated α-Syn pathology, as revealed by enhanced α-Syn insolubility and phosphorylation, was determined in PD-derived mDANs compared with PD CPNs. PD-derived mDANs exhibited higher levels of reactive oxygen species and protein nitration levels compared with CPNs, which might underlie elevated α-Syn pathology observed in mDANs. Finally, increased neuronal death was observed in PD-derived mDANs compared to PD CPNs and to control mDANs and CPNs. Our results reveal, for the first time, a higher α-Syn pathology, oxidative stress level, and neuronal death rate in human PD mDANs compared with PD CPNs from the same patient. The finding implies the contribution of pathogenic α-Syn, probably induced by oxidative stress, to selective vulnerability of substantia nigra dopaminergic neurons in human PD.
CRIS-Team Scopus Importer:2020-05-26

Demyelinating disease and anti-N-methyl-D-aspartate receptor immunoglobulin G antibodies: a case report - Waschbisch, Anne; Kallmünzer, Bernd; Schwab, Stefan; Gölitz, Philipp; Vincent, Angela; Lee, De Hyung; Linker, Ralf (BMC Research Notes, 2014)
Anti-N-methyl-D-aspartate receptor immunoglobulin G antibodies directed against the GluN1 subunit are considered highly specific for anti-N-methyl-D-aspartate receptor encephalitis, a severe clinical syndrome characterized by seizures, psychiatric symptoms, orofacial dyskinesia and autonomic dysfunction.Here we report a 33 year old Caucasian male patient with clinically definite multiple sclerosis who was found to be positive for anti-N-methyl-D-aspartate receptor antibodies. Rituximab therapy was initiated. On the 18 months follow-up visit the patient was found to be clinically stable, without typical signs of anti-N-methyl-D-aspartate receptor encephalitis.Our findings add to the growing evidence for a possible association between anti-N-methyl-D-aspartate receptor encephalitis and demyelinating diseases.
EVALuna2:22345

Dentate gyrus astrocytes exhibit layer-specific molecular, morphological and physiological features - Karpf, Julian; Unichenko, Petr; Chalmers, Nicholas; Beyer, Felix; Wittmann, Marie-Theres; Schneider, Julia; Fidan, Elif; Reis, André; Beckervordersandforth, Jan; Brandner, Sebastian; Liebner, Stefan; Falk, Sven; et al. (Nature Neuroscience, 2022)
Neuronal heterogeneity has been established as a pillar of higher central nervous system function, but glial heterogeneity and its implications for neural circuit function are poorly understood. Here we show that the adult mouse dentate gyrus (DG) of the hippocampus is populated by molecularly distinct astrocyte subtypes that are associated with distinct DG layers. Astrocytes localized to different DG compartments also exhibit subtype-specific morphologies. Physiologically, astrocytes in upper DG layers form large syncytia, while those in lower DG compartments form smaller networks. Astrocyte subtypes differentially express glutamate transporters, which is associated with different amplitudes of glutamate transporter-mediated currents. Key molecular and morphological features of astrocyte diversity in the mice DG are conserved in humans. This adds another layer of complexity to our understanding of brain network composition and function, which will be crucial for further studies on astrocytes in health and disease.
CRIS-Team Scopus Importer:2022-12-09

Depletion of donor-specific anti-HLA A2 alloantibodies in a hematopoietic cell transplant recipient using directed mismatched platelet transfusions - Spriewald, Bernd M.; Bach, Christian; Zingsem, Jürgen; Strobel, Joachim; Winkler, Jürgen; Mackensen, Andreas; Rösler, Wolf (Bone Marrow Transplantation, 2018)
EVALuna2:34275

Design of TRUST, a non-interventional, multicenter, 3-year prospective study investigating an integrated patient management approach in patients with relapsing-remitting multiple sclerosis treated with natalizumab - Ziemssen, Tjalf; Gass, Achim; Wuerfel, Jens; Bayas, Antonios; Tackenberg, Bjoern; Limmroth, Volker; Linker, Ralf; Maeurer, Mathias; Haas, Judith; Stangel, Martin; Meergans, Matthias; Harlin, Olof; et al. (BMC Neurology, 2016)
Natalizumab provides rapid and high-efficacy control of multiple sclerosis disease activity with long-term stabilization. However, the benefits of the drug are countered by a risk of developing progressive multifocal leukoencephalopathy in patients infected with the John Cunningham Virus. Close monitoring is required in patients with increased progressive multifocal leukoencephalopathy risk receiving natalizumab in the long-term for an optimal benefit-risk evaluation. Standardized high-quality monitoring procedures may provide a superior basis for individual benefit and risk evaluation and thus improve treatment decisions. The non-interventional study TRUST was designed to capture natalizumab effectiveness under real-life conditions and to examine alternate approaches for clinical assessments, magnetic resonance imaging monitoring and use of biomarkers for progressive multifocal leukoencephalopathy risk stratification.TRUST is a non-interventional, multicenter, prospective cohort study conducted at approximately 200 German neurological centers. The study is intended to enroll 1260 relapsing-remitting multiple sclerosis patients with ongoing natalizumab therapy for at least 12 months. Patients will be followed for a period of 3 years, irrespective of treatment changes after study start. Data on clinical, subclinical and patient-centric outcomes will be documented in order to compare the effectiveness of continuous versus discontinued natalizumab treatment. Furthermore, the type and frequency of clinical, magnetic resonance imaging and biomarker assessments, reasons for continuation or discontinuation of therapy and the safety profile of natalizumab will be collected to explore the impact of a systematic patient management approach and its potential impact on patient outcome. Specifically, the role of biomarkers, the use of expert opinions, the impact of high-frequency magnetic resonance imaging assessment for early progressive multifocal leukoencephalopathy detection and the role of additional radiological and clinical expert advice will be explored.TRUST was initiated in spring 2014 and enrollment is anticipated to be completed by mid 2016. Annual interim analyses will deliver continuous information and transparency with regard to the patient cohorts and the completeness and quality of data as well as closely monitor any safety signals in the natalizumab-treated cohort. The study's results may provide insights into opportunities to improve the benefit-risk assessment in clinical practice and support treatment decisions.
EVALuna2:22446

Detecting Misfolded α-Synuclein in Blood Years before the Diagnosis of Parkinson's Disease - Kluge, Annika; Schaeffer, Eva; Bunk, Josina; Sommerauer, Michael; Röttgen, Sinah; Schulte, Claudia; Roeben, Benjamin; von Thaler, Anna Katharina; Welzel, Julius; Lucius, Ralph; Heinzel, Sebastian; Xiang, Wei; et al. (Movement Disorders, 2024)
Background: Identifying individuals with Parkinson's disease (PD) already in the prodromal phase of the disease has become a priority objective for opening a window for early disease-modifying therapies. Objective: The aim was to evaluate a blood-based α-synuclein seed amplification assay (α-syn SAA) as a novel biomarker for diagnosing PD in the prodromal phase. Methods: In the TREND study (University of Tuebingen) biennial blood samples of n = 1201 individuals with/without increased risk for PD were taken prospectively over 4 to 10 years. We retrospectively analyzed blood samples of 12 participants later diagnosed with PD during the study to detect and amplify pathological α-syn conformers derived from neuronal extracellular vesicles using (1) immunoblot analyses with an antibody against these conformers and (2) an α-syn-SAA. Additionally, blood samples of n = 13 healthy individuals from the TREND cohort and n = 20 individuals with isolated rapid eye movement sleep behavior disorder (iRBD) from the University Hospital Cologne were analyzed. Results: All individuals with PD showed positive immunoblots and a positive α-syn SAA at the time of diagnosis. Moreover, all PD patients showed a positive α-syn SAA 1 to 10 years before clinical diagnosis. In the iRBD cohort, 30% showed a positive α-syn SAA. All healthy controls had a negative SAA. Conclusions: We here demonstrate the possibility to detect and amplify pathological α-syn conformers in peripheral blood up to 10 years before the clinical diagnosis of PD in individuals with and without iRBD. The findings of this study indicate that this blood-based α-syn SAA assay has the potential to serve as a diagnostic biomarker for prodromal PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
CRIS-Team Scopus Importer:2024-05-03
Keywords: biomarker; neuron-derived extracellular vesicles; Parkinson's disease; seed amplification assay; α-synuclein

Detection of Gait From Continuous Inertial Sensor Data Using Harmonic Frequencies - Ullrich, Martin; Küderle, Arne; Hannink, Julius; Del Din, Silvia; Gaßner, Heiko; Marxreiter, Franz; Klucken, Jochen; Eskofier, Björn; Kluge, Felix (IEEE Journal of Biomedical and Health Informatics, 2020)
Mobile gait analysis using wearable inertial measurement units (IMUs) provides valuable insights for the assessment of movement impairments in different neurological and musculoskeletal diseases, for example Parkinson's disease (PD). The increase in data volume due to arising long-term monitoring requires valid, robust and efficient analysis pipelines. In many studies an upstream detection of gait is therefore applied. However, current methods do not provide a robust way to successfully reject non-gait signals. Therefore, we developed a novel algorithm for the detection of gait from continuous inertial data of sensors worn at the feet. The algorithm is focused not only on a high sensitivity but also a high specificity for gait. Sliding windows of IMU signals recorded from the feet of PD patients were processed in the frequency domain. Gait was detected if the frequency spectrum contained specific patterns of harmonic frequencies. The approach was trained and evaluated on 150 clinical measurements containing standardized gait and cyclic movement tests. The detection reached as sensitivity of 0.98 and a specificity of 0.96 for the best sensor configuration (angular rate around the medio-lateral axis). On an independent validation data set including 203 unsupervised, semi-standardized gait tests, the algorithm achieved a sensitivity of 0.97. Our algorithm for the detection of gait from continuous IMU signals works reliably and showed promising results for the application in the context of free-living and non-standardized monitoring scenario
Keywords: Accelerometer; Fourier transform; Gyroscope; Parkinsons disease; Walking bouts

Detection of neuron-derived pathological alpha-synuclein in blood - Kluge, Annika; Bunk, Josina; Schaeffer, Eva; Drobny, Alice; Xiang, Wei; Knacke, Henrike; Bub, Simon; Lueckstaedt, Wiebke; Arnold, Philipp; Lucius, Ralph; Berg, Daniela; Zunke, Friederike (Brain, 2022)
To date, no reliable clinically applicable biomarker has been established for Parkinson's disease. Our results indicate that a long anticipated blood test for Parkinson's disease may be realized. Following the isolation of neuron-derived extracellular vesicles of Parkinson's disease patients and non-Parkinson's disease individuals, immunoblot analyses were performed to detect extracellular vesicle-derived alpha-synuclein. Pathological alpha-synuclein forms derived from neuronal extracellular vesicles could be detected under native conditions and were significantly increased in all individuals with Parkinson's disease and clearly distinguished disease from the non-disease state. By performing an alpha-synuclein seeding assay these soluble conformers could be amplified and seeding of pathological protein folding was demonstrated. Amplified alpha-synuclein conformers exhibited beta-sheet-rich structures and a fibrillary appearance. Our study demonstrates that the detection of pathological alpha-synuclein conformers from neuron-derived extracellular vesicles from blood plasma samples has the potential to evolve into a blood-biomarker of Parkinson's disease that is still lacking so far. Moreover, the distribution of seeding-competent alpha-synuclein within blood exosomes sheds a new light of pathological disease mechanisms in neurodegenerative disorders.
CRIS-Team WoS Importer:2022-07-01
Keywords: α-synuclein; Parkinson’s disease; biomarker; neuron-derived extracellular vesicles; seeding assay

Detection of unsupervised standardized gait tests from real-world inertial sensor data in Parkinson’s disease - Ullrich, Martin; Mücke, Annika; Küderle, Arne; Roth, Nils; Gladow, Till; Gaßner, Heiko; Marxreiter, Franz; Klucken, Jochen; Eskofier, Björn; Kluge, Felix (IEEE Transactions on Neural Systems and Rehabilitation Engineering, 2021)
Gait tests as part of home monitoring study protocols for patients with movement disorders may provide valuable standardized anchor-points for real-world gait analysis using inertial measurement units (IMUs). However, analyzing unsupervised gait tests relies on reliable test annotations by the patients requiring a potentially error-prone interaction with the recording system. To overcome this limitation, this work presents a novel algorithmic pipeline for the automated detection of unsupervised standardized gait tests from continuous real-world IMU data. In a study with twelve Parkinson’s disease patients, we recorded real-world gait data over two weeks using foot-worn IMUs. During continuous daily recordings, the participants performed series of three consecutive 4x10-Meters-Walking-Tests (4x10MWTs) at different walking speeds, besides their usual daily-living activities. The algorithm first detected these gait test series using a gait sequence detection algorithm, a peak enhancement pipeline, and subsequence Dynamic Time Warping and then decomposed them into single 4x10MWTs based on the walking speed. In the evaluation with 419 available gait test series, the detection reached an F1-score of 88.9% and the decomposition an F1-score of 94.0%. A concurrent validity evaluation revealed very good agreement between spatio-temporal gait parameters derived from manually labelled and automatically detected 4x10MWTs. Our algorithm allows to remove the burden of system interaction from the patients and reduces the time for manual data annotation for researchers. The study contributes to an improved automated processing of real-world IMU gait data and enables a simple integration of standardized tests into continuous long-term recordings. This will help to bridge the gap between supervised and unsupervised gait assessment.
Keywords: Machine learning; activity recognition; accelerometer; gyroscope; legged locomotion; protocol; diseases; pipelines; monitoring; hospitals; annotations

Detection radius of EMG for fasciculations: Empiric study combining ultrasonography and electromyography. - Regensburger, Martin; Tenner, Felix; Möbius, Cornelia; Schramm, A (Clinical Neurophysiology, 2017)
OBJECTIVE The aims of this study were to investigate the detection radius and sensitivity of EMG for fasciculations. METHODS Muscle ultrasonography was performed simultaneously to EMG recordings in patients with fasciculations in the context of amyotrophic lateral sclerosis. Ultrasonography and EMG parameters were analyzed for selected fasciculations. RESULTS A total of 381 fasciculations were detected by ultrasonography in 18 muscles of 10 patients. Out of these, 125 (33%) were EMG-negative. In contrast, none of the fasciculations detected by EMG were ultrasonography-negative. EMG detection probability decreased significantly with increasing distance from the center of the fasciculation. EMG detection rate was 98% when the EMG needle was located within the fasciculation and 50% at 7.75 mm distance from the fasciculation center. In addition, EMG detection depended significantly on cross-sectional area of the fasciculation and presence of neurogenic changes. CONCLUSIONS For detecting the same fasciculations, EMG is less sensitive than ultrasonography. EMG detection probability decreases sharply at a distance comparable to motor unit size. SIGNIFICANCE These results extend previous knowledge about superior sensitivity of ultrasonography for fasciculations. Moreover, our novel bimodal detection method provides first in vivo data about the EMG detection radius for fasciculations in a clinical setting.

Development and clinical validation of inertial sensor-based gait-clustering methods in Parkinson's disease - Nguyen, An; Roth, Nils; Haji Ghassemi, Nooshin; Hannink, Julius; Seel, Thomas; Klucken, Jochen; Gaßner, Heiko; Eskofier, Björn (Journal of neuroEngineering and rehabilitation, 2019)
BackgroundGait symptoms and balance impairment are characteristic indicators for the progression in Parkinson's disease (PD). Current gait assessments mostly focus on straight strides with assumed constant velocity, while acceleration/deceleration and turning strides are often ignored. This is either due to the set up of typical clinical assessments or technical limitations in capture volume. Wearable inertial measurement units are a promising and unobtrusive technology to overcome these limitations. Other gait phases such as initiation, termination, transitioning (between straight walking and turning) and turning might be relevant as well for the evaluation of gait and balance impairments in PD.MethodIn a cohort of 119 PD patients, we applied unsupervised algorithms to find different gait clusters which potentially include the clinically relevant information from distinct gait phases in the standardized 4x10 m gait test. To clinically validate our approach, we determined the discriminative power in each gait cluster to classify between impaired and unimpaired PD patients and compared it to baseline (analyzing all straight strides).ResultsAs a main result, analyzing only one of the gait clusters constant, non-constant or turning led in each case to a better classification performance in comparison to the baseline (increase of area under the curve (AUC) up to 19% relative to baseline). Furthermore, gait parameters (for turning, constant and non-constant gait) that best predict motor impairment in PD were identified.ConclusionsWe conclude that a more detailed analysis in terms of different gait clusters of standardized gait tests such as the 4x10 m walk may give more insights about the clinically relevant motor impairment in PD patients.
CRIS-Team WoS Importer:2019-07-12

Development of a questionnaire to measure patient-relevant needs and benefits in the treatment of epilepsy (PBI-Epilepsy) - Janke, Toni Maria; Cuny, Jeanne; Blome, Christine; Wittig-Moßner, Doris; Hamer, Hajo (Epilepsy and Behavior, 2025)
Objective: Therapeutic goals in epilepsy treatment may be highly individual. The aim of the present study was to develop a questionnaire assessing patients’ needs and benefits of epilepsy treatment, the Patient Benefit Index on Epilepsy (PBI-Epilepsy). Methods: We recruited adult patients during their stay at a university based epilepsy centre. Patients completed a survey asking about their burden and treatment goals. Data were categorised using qualitative content analysis. The final category system was discussed in an expert panel. The questionnaire was pre-tested using cognitive debriefing and adapted until no changes were required anymore. Results: In the open survey, 25 people with epilepsy participated (60.0 % female, 33.2 years, 1–55 years epilepsy). The final category system included nine main categories (namely psyche, working life, seizures, therapy, leisure activities, social relationships, mobility, body, everyday life activities). From this, the expert panel developed a first draft of the PBI-Epilepsy. The questionnaire went through five rounds of cognitive debriefing with 29 patients (51.7 % female, 34.6 years, 2–37 years epilepsy). We decided to develop two versions of the questionnaire depending on the patient's treatment (medical or surgical). A bipolar response scale was used in the part asking about treatment benefits, as epilepsy treatment can lead to both improvement and deterioration. The final questionnaire consists of two parts (patient needs and treatment benefits) each encompassing 21 items. Conclusion: We aimed to reflect the wide range of issues that are relevant for people with epilepsy while developing a questionnaire that is short and easy for patients to understand.
CRIS-Team Scopus Importer:2024-12-06
Keywords: Patient benefit; Patient benefit index; Patient-reported outcome; PBI; Questionnaire development

Dexamethasone in Patients with Spontaneous Intracerebral Hemorrhage: An Updated Meta-Analysis - Wintzer, Stephanie; Heckmann, Josef Georg; Huttner, Hagen; Schwab, Stefan (Cerebrovascular Diseases, 2020)
Background: Spontaneous intracerebral hemorrhage (ICH) is a frequent cerebrovascular disorder and still associated with high mortality and poor clinical outcomes. The purpose of this review was to update a 15-year-old former meta-Analysis on randomized clinical trials (RCTs) addressing the question of whether ICH patients treated with dexamethasone have better outcomes than controls. Methods: The electronic databases PubMed, SCOPUS, and Cochrane as well as web platforms on current clinical trials were searched for the years 1970-2020 without constriction on language. Data were extracted and outcomes were pooled for conventional and cumulative meta-Analysis using a commercial software program (www.Meta-Analysis.com). Results: Finally, 7 RCTs were identified and analyzed including 248 participants in the dexamethasone groups and 242 in the control groups. Five studies showed a high risk of bias. The overall relative risk (RR) for death was 1.32 (95% confidence interval [CI] 0.99-1.76; p = 0.06) and did not differ significantly between the 2 groups. After exclusion of studies with high risk of bias, the RR for death was 1.37 (95% CI 0.54-3.42; p = 0.51). The RR for poor outcome did not differ significantly between the 2 groups analyzed for all included studies (RR = 0.69; 95% CI 0.47-1; p = 0.05) and after exclusion of studies with high risk of bias (RR = 0.7; 95% CI 0.45-1.08; p = 0.11). The RR for complications did not differ significantly including all studies (RR = 1.29; 95% CI 0.77-2.17; p = 0.34) and after exclusion of studies with high risk of bias (RR = 1.27; 95% CI 0.18-8.89; p = 0.81). The cumulative statistics delivered no other results; however, it pointed out fewer complications over time in the dexamethasone group. Conclusion: Clear evidence of a beneficial or negative effect of dexamethasone is still lacking. Modern RCTs or observational studies with propensity design are necessary to evaluate the efficacy and safety of treatment with dexamethasone in patients with ICH.
CRIS-Team Scopus Importer:2020-10-02

Diagnosis of spontaneous cervical artery dissection may be associated with increased prevalence of posttraumatic stress disorder - Speck, Verena; Noble, Adam; Kollmar, Rainer; Schenk, Thomas (Journal of Stroke and Cerebrovascular Diseases, 2014)
Receiving information that one has a dissected cervical artery, which can cause a stroke at any time, is obviously traumatic, but details about the psychiatric and psychosocial sequelae are not known. We investigated the prevalence of and risk factors for posttraumatic stress disorder (PTSD) in patients with spontaneous cervical artery dissection (CD) and the impact of PTSD on their psychosocial functioning.Patients admitted because of CD between 2006 and 2010 were retrospectively examined using a diagnostic PTSD measure (Posttraumatic Diagnostic Scale). Patients between 2011 and 2012 were examined prospectively. To identify potential predictors for PTSD, we examined all patients' stress coping strategies (brief COPE inventory), anxiety and depression (Hospital Anxiety and Depression Scale), impairment by preventive medication, time since diagnosis and their neurologic (modified Rankin Scale) and cognitive status. To identify the psychosocial impact of PTSD, we examined quality of life (Short-Form 36).Data of 47 retrospectively contacted patients and 15 prospectively examined patients were included. Twenty-eight patients (45.2%) met the diagnostic criteria for PTSD. A significantly reduced health-related quality of life (HRQoL) was found in 27 patients (43.5%) for mental health and in 8 patients (12.9%) for physical health. Results of logistic regression analysis revealed that the use of maladaptive coping strategies was predictive of the disorder (P < .0001). Age, sex, mRS score, impairment caused by medication, and time since diagnosis were not predictive for PTSD. The presence of PTSD itself was the only significant predictor for reduced mental HRQol (P = .0004). Age, sex, mRS score, impairment caused by medication, and total Hospital Anxiety and Depression Scale score were not predictive for reduced mental HRQoL.PTSD seems to occur frequently in patients with CD and is associated with reduced mental HRQoL. Because the presence of a maladaptive coping style is correlated with PTSD, teaching patients better coping skills might be helpful.
EVALuna2:22243

Diagnostic value of prehospital ECG in acute stroke patients - Bobinger, Tobias; Kallmnzer, Bernd; Kopp, Markus; Kurka, Natalia; Heider, Stefan; Schwab, Stefan; Köhrmann, Martin; Arnold, Martin (Neurology, 2017)
To investigate the diagnostic yield of prehospital ECG monitoring provided by emergency medical services in the case of suspected stroke.Consecutive patients with acute stroke admitted to our tertiary stroke center via emergency medical services and with available prehospital ECG were prospectively included during a 12-month study period. We assessed prehospital ECG recordings and compared the results to regular 12-lead ECG on admission and after continuous ECG monitoring at the stroke unit.Overall, 259 patients with prehospital ECG recording were included in the study (90.3% ischemic stroke, 9.7% intracerebral hemorrhage). Atrial fibrillation (AF) was detected in 25.1% of patients, second-degree or greater atrioventricular block in 5.4%, significant ST-segment elevation in 5.0%, and ventricular ectopy in 9.7%. In 18 patients, a diagnosis of new-onset AF with direct clinical consequences for the evaluation and secondary prevention of stroke was established by the prehospital recordings. In 2 patients, the AF episodes were limited to the prehospital period and were not detected by ECG on admission or during subsequent monitoring at the stroke unit. Of 126 patients (48.6%) with relevant abnormalities in the prehospital ECG, 16.7% received medical antiarrhythmic therapy during transport to the hospital, and 6.4% were transferred to a cardiology unit within the first 24 hours in the hospital.In a selected cohort of patients with stroke, the in-field recordings of the ECG detected a relevant rate of cardiac arrhythmia. The results can add to the in-hospital evaluation and should be considered in prehospital care of acute stroke.
EVALuna2:22506

Diagnostic value of the 2017 McDonald criteria in patients with a first demyelinating event suggestive of relapsing-remitting multiple sclerosis - Lee, De-Hyung; Peschke, Maren; Utz, K. S.; Linker, R. A. (European Journal of Neurology, 2019)
Background and purposeFor the diagnosis of relapsing-remitting multiple sclerosis (RRMS), the revised 2017 McDonald criteria include cerebrospinal fluid specific oligoclonal bands as a new criterion for dissemination in time. Amongst other things, one expectation of the new criteria is to marginalize the diagnosis of clinically isolated syndrome (CIS), thus allowing for a faster and at the same time still reliable diagnosis of RRMS.
CRIS-Team WoS Importer:2019-02-27

Diagnostik bei Polyneuropathien - Heuss, D. (Internist, 2020)
The diagnosis of polyneuropathy (PNP) is based on the anamnesis and description of complaints of the patient and clinical findings. The type of distribution as well as known diseases and drug toxic factors can provide indications. Electromyography and electroneurography can be used to differentiate between axonal and demyelinating PNP. The laboratory examinations are initially directed towards frequent and treatable causes. These are then expanded depending on the suspected diagnosis. Analysis of cerebrospinal fluid (CSF) is facultative and should be carried out when there is a suspicion of a certain form of PNP with CSF findings indicative of the diagnosis. Nerve biopsy is indicated when the etiology of a severe or progressive PNP cannot be clarified by less invasive means and can have consequences for the treatment. A genetic investigation can be meaningful with a positive family anamnesis or with typical signs of hereditary PNP. Depending on the neuropathy and context, the diagnostic approach is structured differently. The special diagnostics for small fiber neuropathy and amyloid neuropathy as well as for diabetes and alcohol abuse are dealt with in detail in this article. Numerous cases of polyneuropathy remain unexplained and regularly have a favourable prognosis.
CRIS-Team Scopus Importer:2020-03-13
Keywords: Alcohol abuse; Amyloid neuropathies; Diabetes mellitus; Diagnostic certainty; Small fiber neuropathy

Diagnostik Lumbar Puncture - Step by Step - Siedler, Gabriela; Kallmünzer, Bernd; Schwab, Stefan (Deutsche Medizinische Wochenschrift, 2019)
Performing a diagnostic lumbar puncture is an essential clinical skill for the clinician. The procedure is of high importance for both, the emergency care for patients with suspected infection of the cerebral nervous system or subarachnoidal hemorrhage, as well as the elective diagnostic work up of chronic disease including multiple sclerosis and dementia. Furthermore the technique's principles are applied for spinal anesthesia or the intrathecal administration of drugs. This article describes a Standard Operating Procedure for the lumbar puncture step by step. Based on the latest evidence, it particularly focusses on clinically relevant questions and practical aspects.
EVALuna2:204469

Die Geschichte des ‚Freezing-of-gait‘ beim Parkinson-Syndrom – vom Phänomen zum Symptom - Klucken, Jochen; Winkler, Jürgen; Krüger, Rejko; Jost, Wolfgang (Fortschritte der Neurologie - Psychiatrie, 2020)
The background of the freezing-of-gait (FOG) phenomenon in Parkinson's syndrome is presented in this review. The following issues are addressed: characterization of the symptom freezing and its subtypes that challenge standardized diagnostic procedures; available assessment methods generating freezing-related parameters that not only support clinical studies but can also be applied in everyday care, and current therapy options. FOG exists in different subtypes, and clinical and diagnostic definitions are limited by subjective characterization and semi-standardized tests. FOG-specific drug options are not existing, apart from the optimization of dopaminergic medication, which may also be due to the poor discriminatory power of standardized diagnostics. This is also true for deep brain stimulation. Both of these therapeutic options may be due not only to the complex neural network alterations as a motor-control correlate of FOG, but also because of challenging diagnostic assessments methodologies. Innovative, wearable, sensor-based diagnostic strategies are currently being developed, and supportive therapies using tools and technologies focusing on 'cueing' are becoming increasingly well accepted. Even though high level evidence is missing, they provide a helpful treatment option for individualized therapy. It can be assumed that these options will become particularly popular due to technological progress and likely alter the everyday treatment challenges faced by doctors and therapists.
CRIS-Team Scopus Importer:2020-10-02

Die Relevanz der neuen DIVI-Empfehlung zur Struktur und Ausstattung von Intensivstationen für die Neuromedizin - Waydhas, Christian; Hoffmann, Florian; van den Hooven, Thomas; Markewitz, Andreas; Riessen, Reimer; Schwab, Stefan; Unterberg, Andreas (Der Nervenarzt, 2023)
EVALuna2:536993

Dietary fatty acids and susceptibility to multiple sclerosis - Haase, Stefanie; Haghikia, Aiden; Gold, Ralf; Linker, Ralf (Multiple sclerosis journal, 2018)
The gut microbiome as well as dietary habits have recently been established as environmental contributors to the pathogenesis of multiple sclerosis (MS), a T-cell-mediated autoimmune disease of the central nervous system (CNS).To summarize recent findings on the Janus-faced effects of dietary short-chain fatty acids (SCFAs) and long-chain fatty acids (LCFAs) on T-cell immunity with a special focus on the gut and the microbiome as an interface linking diet and T-cell responses during MS.Review article.The autoimmune basis of MS most likely stems from an imbalance between pro-inflammatory T helper cell (Th)1 and Th17 cells and anti-inflammatory or regulatory mechanisms including regulatory T cells (Treg). Hence, the rationale of currently available therapeutic interventions is to either suppress pathogenic Th1/Th17 and/or to foster Treg responses. Dietary fatty acids are often discussed for their detrimental role in MS. However, recent studies investigating saturated fatty acids in animal models of MS revealed harmful as well as beneficial effects depending on their aliphatic chain length.Dietary SCFAs constitute interesting candidates as safe and potent add-on therapy in the immunomodulatory treatment armamentarium for relapsing-remitting MS.
EVALuna2:22562

Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine - Haghikia, Aiden; Joerg, Stefanie; Duscha, Alexander; Berg, Johannes; Manzel, Arndt; Waschbisch, Anne; Hammer, Anna; Lee, De-Hyung; May, Caroline; Wilck, Nicola; Balogh, Andras; Ostermann, Annika I.; et al. (Immunity, 2015)
Growing empirical evidence suggests that nutrition and bacterial metabolites might impact the systemic immune response in the context of disease and autoimmunity. We report that long-chain fatty acids (LCFAs) enhanced differentiation and proliferation of T helper 1 (Th1) and/or Th17 cells and impaired their intestinal sequestration via p38-MAPK pathway. Alternatively, dietary short-chain FAs (SCFAs) expanded gut T regulatory (Treg) cells by suppression of the JNK1 and p38 pathway. We used experimental autoimmune encephalomyelitis (EAE) as a model of T cell-mediated autoimmunity to show that LCFAs consistently decreased SCFAs in the gut and exacerbated disease by expanding pathogenic Th1 and/or Th17 cell populations in the small intestine. Treatment with SCFAs ameliorated EAE and reduced axonal damage via long-lasting imprinting on lamina-propria-derived Treg cells. These data demonstrate a direct dietary impact on intestinal-specific, and subsequently central nervous system-specific, Th cell responses in autoimmunity, and thus might have therapeutic implications for autoimmune diseases such as multiple sclerosis.
EVALuna2:22371

Differences in Intrusive Memory Experiences in Post-traumatic Stress Disorder after Single, Re- and Prolonged Traumatization - Mueller, Helge H.; Möller, Sebastian; Jenderek, Konstanze; Stroebel, Armin; Wiendieck, Kurt; Sperling, Wolfgang (Frontiers in Psychology, 2016)
Intrusive memory experiences (IMEs) are a common symptom of post-traumatic stress disorder (PTSD). Sensory perceptions of IMEs in the PTSD context vary substantially. The present research examined 20 patients with a single trauma, 20 re-traumatized patients and 80 Holocaust-traumatized patients who suffered from PTSD. Our results revealed significant differences in IME frequency based on the types of trauma experience. The findings suggest that patients with prolonged (Holocaust) traumata suffered from visual (65%) and combined visual/acoustic intrusive memories (29%), whereas visual memory experiences were most frequent (90%) among single-trauma patients. The trauma experience and the intrusive memory trigger stimulus were interdependent. The type of trauma critically affects the traumatic experience. Future studies should focus on these findings to improve PTSD therapeutic options.
EVALuna2:23807

Differential influence of hippocampal subfields to memory formation: insights from patients with temporal lobe epilepsy - Coras, Roland; Pauli, Elisabeth; Li, Jinmei; Schwarz, Michael; Roessler, Karl; Buchfelder, Michael; Hamer, Hajo; Stefan, Hermann; Blümcke, Ingmar (Brain, 2014)
To clarify the anatomical organization of human memory remains a major challenge in clinical neuroscience. Experimental data suggest dentate gyrus granule cells play a major role in memory acquisition, i.e. pattern separation and rapid pattern completion, whereas hippocampal CA1 neurons are implicated in place memory and autobiographical memory retrieval. Patients with temporal lobe epilepsy present with a broad spectrum of memory impairment, which can be assessed during clinical examination. Although long seizure histories may contribute to a pathophysiological reorganization of functional connectivity, surgical resection of the epileptic hippocampus offers a unique possibility to anatomically study the differential contribution of hippocampal subfields to compromised learning and memory in humans. Herein, we tested the hypothesis of hippocampal subfield specialization in a series of 100 consecutive patients with temporal lobe epilepsy submitted to epilepsy surgery. Memory profiles were obtained from intracarotid amobarbital testing and non-invasive verbal memory assessment before surgery, and correlated with histopathologically quantified cell loss pattern in hippocampal subfields obtained from the same patients using the new international consensus classification for hippocampal sclerosis proposed by the International League against Epilepsy (HS ILAE). Interestingly, patients with CA1 predominant cell loss (HS ILAE Type 2; n = 13) did not show declarative memory impairment and were indistinguishable from patients without any hippocampal cell loss (n = 19). In contrast, 63 patients with neuronal loss affecting all hippocampal subfields including CA1, CA4 and dentate gyrus (HS ILAE Type 1), or predominant cell loss in CA4 and partially affecting also CA3 and dentate gyrus (HS ILAE Type 3, n = 5) showed significantly reduced declarative memory capacities (intracarotid amobarbital testing: P < 0.001; verbal memory: P < 0.05). Our results suggested an alternative model of how memory processing can be organized amongst hippocampal subfields, and that CA1 pyramidal cells are less critically involved in declarative human memory acquisition compared to dentate gyrus granule cells or CA4/CA3 pyramidal cells.
EVALuna2:7242

Differentiation of atypical Parkinson syndromes - Hoeglinger, Guenter U.; Kassubek, Jan; Csoti, Ilona; Ehret, Reinhard; Herbst, Heinz; Wellach, Ingmar; Winkler, Jürgen; Jost, Wolfgang H. (Journal of Neural Transmission, 2017)
In distinction to idiopathic Parkinson's disease (PD), the diagnosis of atypical Parkinson syndromes comprises dementia with Lewy bodies (DLB), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). We set out to write a state-of-the-art guideline as to which investigations and examinations help to differentiate PD vs. atypical Parkinson syndromes in clinical routine.
EVALuna2:36375

Dimethyl fumarate in multiple sclerosis: latest developments, evidence and place in therapy - Linker, Ralf; Haghikia, Aiden (Therapeutic Advances in Chronic Disease, 2016)
Dimethyl fumarate (DMF) is one of the newer additions to the armamentarium of potent immunomodulators for the treatment of relapsing-remitting multiple sclerosis (RRMS). After more than 2 years of real-world experience and more than 190,000 patients currently treated with DMF worldwide, it is a good timepoint to review the experience gathered so far and to re-evaluate the potential of this first-line oral multiple sclerosis (MS) drug. Post-hoc analyses of clinical and magnetic resonance imaging (MRI) data, some comprising more than 6 years of drug exposure including patients from the clinical trials, and the overall notion in clinical practice widely confirm the good efficacy of DMF in RRMS. Despite an overall good safety profile, it became also clear that the necessary clinical vigilance while using DMF may not be neglected. So far, four reported cases of progressive multifocal leukoencephalopathy (PML), a towering shadow over many MS therapies, warrant proper attention in newly-updated risk management plans. This review recapitulates efficacy and safety aspects of DMF therapy in relation to reported data from the pivotal clinical trials. In addition, we summarize recent insights into DMF mechanisms of action drawn from the field of basic research which may have important implications for clinical practice.
EVALuna2:22549

Direct delivery of antigens to dendritic cells via antibodies specific for endocytic receptors as a promising strategy for future therapies - Lehmann, Christian; Heger, Lukas; Heidkamp, Gordon Frederik; Baranska, Anna; Lühr, Jennifer; Hoffmann, Alana; Dudziak, Diana (Vaccines, 2016)
Dendritic cells (DCs) are the most potent professional antigen presenting cells and are therefore indispensable for the control of immunity. The technique of antibody mediated antigen targeting to DC subsets has been the basis of intense research for more than a decade. Many murine studies have utilized this approach of antigen delivery to various kinds of endocytic receptors of DCs both in vitro and in vivo. Today, it is widely accepted that different DC subsets are important for the induction of select immune responses. Nevertheless, many questions still remain to be answered, such as the actual influence of the targeted receptor on the initiation of the immune response to the delivered antigen. Further efforts to better understand the induction of antigen-specific immune responses will support the transfer of this knowledge into novel treatment strategies for human diseases. In this review, we will discuss the state-of-the-art aspects of the basic principles of antibody mediated antigen targeting approaches. A table will also provide a broad overview of the latest studies using antigen targeting including addressed DC subset, targeted receptors, outcome, and applied coupling techniques.
Created from Fastlane, Scopus look-up
Keywords: Antigen targeting; Antigen targeting antibodies; Cancer; CLR; DC; DCIR; DEC205; Dendritic cell subsets; moDC; Vaccine

Direct imaging of white matter ultrashort T2∗ components at 7 Tesla - Müller, Max; Egger, Nico; Sommer, Stefan; Wilferth, Tobias; Meixner, Christian; Laun, Frederik Bernd; Mennecke, Angelika; Schmidt, Manuel; Huhn, Konstantin; Rothhammer, Veit; Uder, Michael; Dörfler, Arnd; et al. (Magnetic Resonance Imaging, 2022)
Purpose: To demonstrate direct imaging of the white matter ultrashort T2∗ components at 7 Tesla using inversion recovery (IR)-enhanced ultrashort echo time (UTE) MRI. To investigate its characteristics, potentials and limitations, and to establish a clinical protocol. Material and methods: The IR UTE technique suppresses long T2∗ signals within white matter by using adiabatic inversion in combination with dual-echo difference imaging. Artifacts arising at 7 T from long T2∗ scalp fat components were reduced by frequency shifting the IR pulse such that those frequencies were inverted likewise. For 8 healthy volunteers, the T2∗ relaxation times of white matter were then quantified. In 20 healthy volunteers, the UTE difference and fraction contrast were evaluated. Finally, in 6 patients with multiple sclerosis (MS), the performance of the technique was assessed. Results: A frequency shift of −1.2 ppm of the IR pulse (i.e. towards the fat frequency) provided a good suppression of artifacts. With this, an ultrashort compartment of (68 ± 6) % with a T2∗ time of (147 ± 58) μs was quantified with a chemical shift of (−3.6 ± 0.5) ppm from water. Within healthy volunteers' white matter, a stable ultrashort T2∗ fraction contrast was calculated. For the MS patients, a significant fraction reduction in the identified lesions as well as in the normal-appearing white matter was observed. Conclusions: The quantification results indicate that the observed ultrashort components arise primarily from myelin tissue. Direct IR UTE imaging of the white matter ultrashort T2∗ components is thus feasible at 7 T with high quantitative inter-subject repeatability and good detection of signal loss in MS.
Created from Fastlane, Scopus look-up
Keywords: 7 Tesla; Multiple sclerosis; Myelin; Relaxometry; Ultrashort echo time (UTE); White matter

Directional coupling of slow and fast hippocampal gamma with neocortical alpha/beta oscillations in human episodic memory - Griffiths, Benjamin J.; Parish, George; Roux, Frederic; Michelmann, Sebastian; van der Plas, Mircea; Kolibius, Luca D.; Chelvarajah, Ramesh; Rollings, David T.; Sawlani, Vijay; Hamer, Hajo; Gollwitzer, Stephanie; Kreiselmeyer, Gernot; et al. (Proceedings of the National Academy of Sciences of the United States of America, 2019)
Episodic memories hinge upon our ability to process a wide range of multisensory information and bind this information into a coherent, memorable representation. On a neural level, these 2 processes are thought to be supported by neocortical alpha/beta desynchronization and hippocampal theta/gamma synchronization, respectively. Intuitively, these 2 processes should couple to successfully create and retrieve episodic memories, yet this hypothesis has not been tested empirically. We address this by analyzing human intracranial electroencephalogram data recorded during 2 associative memory tasks. We find that neocortical alpha/beta (8 to 20 Hz) power decreases reliably precede and predict hippocampal "fast" gamma (60 to 80 Hz) power increases during episodic memory formation; during episodic memory retrieval, however, hippocampal "slow" gamma (40 to 50 Hz) power increases reliably precede and predict later neocortical alpha/beta power decreases. We speculate that this coupling reflects the flow of information from the neocortex to the hippocampus during memory formation, and hippocampal pattern completion inducing information reinstatement in the neocortex during memory retrieval.
EVALuna2:204498

Directly Reprogrammed Human Neurons Retain Aging-Associated Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic Defects - Mertens, Jerome; Paquola, Apua C. M.; Ku, Manching; Hatch, Emily; Boehnke, Lena; Ladjevardi, Shauheen; Mcgrath, Sean; Campbell, Benjamin; Lee, Hyungjun; Herdy, Joseph R.; Goncalves, J. Tiago; Toda, Tomohisa; et al. (Cell Stem Cell, 2015)
Aging is a major risk factor for many human diseases, and in vitro generation of human neurons is an attractive approach for modeling aging-related brain disorders. However, modeling aging in differentiated human neurons has proved challenging. We generated neurons from human donors across a broad range of ages, either by iPSC-based reprogramming and differentiation or by direct conversion into induced neurons (iNs). While iPSCs and derived neurons did not retain aging-associated gene signatures, iNs displayed age-specific transcriptional profiles and revealed age-associated decreases in the nuclear transport receptor RanBP17. We detected an age-dependent loss of nucleocytoplasmic compartmentalization (NCC) in donor fibroblasts and corresponding iNs and found that reduced RanBP17 impaired NCC in young cells, while iPSC rejuvenation restored NCC in aged cells. These results show that iNs retain important aging-related signatures, thus allowing modeling of the aging process in vitro, and they identify impaired NCC as an important factor in human aging.
EVALuna2:25346

Direct Oral Anticoagulant Plasma Levels for the Management of Acute Ischemic Stroke - Marsch, Armin; Macha, Kosmas; Siedler, Gabriela; Breuer, Lorenz; Strasser, Erwin; Engelhorn, Tobias; Dörfler, Arnd; Schwab, Stefan; Kallmünzer, Bernd (Cerebrovascular Diseases, 2019)
Introduction: The management of acute ischemic stroke in patients on direct oral anticoagulants (DOACs) is challenging. However, the substance-specific plasma level could guide treatment decisions on recanalization therapies. We present a plasma-level-based protocol for emergency treatment of stroke patients on oral anticoagulants. Bleeding complications and clinical outcome for patients on DOACs are reported and compared to patients on vitamin K antagonists (VKAs). Methods: In patients with acute ischemic stroke and suspected use of DOACs within 48 h prior to hospital admission, plasma levels were measured using the calibrated Xa-activity (apixaban, edoxaban, rivaroxaban) or the Hemoclot®-assay (dabigatran). Levels <50 ng/mL were supportive for thrombolysis, while high values >100 ng/mL excluded patients from recombinant tissue plasminogen activator use. For patients on VKAs, the cutoff was set at international normalized ratio of 1.7. Endovascular thrombectomy of a large vessel occlusion was performed independently from coagulation testing. Consecutive patients were included in an observational registry. Results: Five hundred and twenty-two patients (261 on VKAs and 261 on DOACs) were included. Thirty patients (11.5%) on VKAs and 24 (9.2%) on DOACs received thrombolysis, followed by mechanical thrombectomy in 10 and 14 patients, respectively. Seventeen patients in each group received thrombectomy only. Symptomatic intracranial hemorrhage associated with thrombolysis occurred in 1 patient on VKA (3.3%) and 1 on DOAC (4.2%; p = 0.872). The turnaround time of specific assays did not show a significant delay in comparison to standard coagulation parameters. Conclusion: DOAC plasma levels could support decisions on emergency treatment of ischemic stroke. Systemic thrombolysis below suggested thresholds appears preliminary feasible and safe without an excess in bleeding complications.
CRIS-Team Scopus Importer:2019-09-24

Direct oral anticoagulants versus Vitamin K antagonists after a recent ischemic stroke or TIA- a pooled individual patient data analysis - Seiffge, David; Paciaroni, Maurizio; Wilson, Duncan; Koga, Masatoshi; Macha, Kosmas; Cappellari, Manuel; Schaedelin, Sabine; Shakeshaft, Clare; Takagi, Masahito; Tsivgoulis, Georgios; Bonetti, Bruno; Kallmünzer, Bernd; et al. (NEUROLOGY, 2019)
CRIS-Team WoS Importer:2019-08-02

Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation - Seiffge, David J.; Paciaroni, Maurizio; Wilson, Duncan; Koga, Masatoshi; Macha, Kosmas; Cappellari, Manuel; Schaedelin, Sabine; Shakeshaft, Clare; Takagi, Masahito; Tsivgoulis, Georgios; Bonetti, Bruno; Kallmünzer, Bernd; et al. (Annals of Neurology, 2019)
Objective: We compared outcomes after treatment with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and a recent cerebral ischemia. Methods: We conducted an individual patient data analysis of seven prospective cohort studies. We included patients with AF and a recent cerebral ischemia (<3 months before starting oral anticoagulation) and a minimum follow-up of 3 months. We analyzed the association between type of anticoagulation (DOAC versus VKA) with the composite primary endpoint (recurrent ischemic stroke [AIS], intracerebral hemorrhage [ICH], or mortality) using mixed-effects Cox proportional hazards regression models; we calculated adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs). Results: We included 4,912 patients (median age, 78 years [interquartile range IQR, 71–84]; 2,331 [47.5%] women; median National Institute of Health Stroke Severity Scale at onset, 5 [IQR, 2–12]); 2,256 (45.9%) patients received VKAs and 2,656 (54.1%) DOACs. Median time from index event to starting oral anticoagulation was 5 days (IQR, 2–14) for VKAs and 5 days (IQR, 2–11) for DOACs (p = 0.53). There were 262 acute ischemic strokes (AISs; 4.4%/year), 71 intracranial hemorrrhages (ICHs; 1.2%/year), and 439 deaths (7.4%/year) during the total follow-up of 5,970 patient-years. Compared to VKAs, DOAC treatment was associated with reduced risks of the composite endpoint (HR, 0.82; 95% CI, 0.67–1.00; p = 0.05) and ICH (HR, 0.42; 95% CI, 0.24–0.71; p < 0.01); we found no differences for the risk of recurrent AIS (HR, 0.91; 95% CI, 0.70–1.19; p = 0.5) and mortality (HR, 0.83; 95% CI, 0.68–1.03; p = 0.09). Interpretation: DOAC treatment commenced early after recent cerebral ischemia related to AF was associated with reduced risk of poor clinical outcomes compared to VKA, mainly attributed to lower risks of ICH. ANN NEUROL 2019.
CRIS-Team Scopus Importer:2019-05-17

Disability-Adjusted Life-Years Associated with Intracerebral Hemorrhage and Secondary Injury - Haupenthal, David; Kuramatsu, Joji; Volbers, Bastian; Sembill, Jochen; Mrochen, Anne; Balk, Stefanie; Hölter, Philip; Lücking, Hannes; Engelhorn, Tobias; Dörfler, Arnd; Schwab, Stefan; Huttner, Hagen; et al. (JAMA Network Open, 2021)
Importance: Intracerebral hemorrhage (ICH) contributes significantly to the global burden of disease. Objective: To examine the association of ICH and secondary injury with disability-adjusted life-years (DALYs) for the individual patient. Design, Setting, and Participants: This cohort study was conducted using data from the Universitätsklinikum Erlangen Cohort of Patients With Spontaneous Intracerebral Hemorrhage study. Consecutive patients admitted to a single tertiary care center from January 1, 2006, to December 31, 2015, were included. The sample comprised patients with oral anticoagulation-associated ICH (OAC-ICH) or primary spontaneous ICH (non-OAC-ICH). Statistical analysis was conducted from October 1 to December 31, 2020. Exposures: ICH occurrence and secondary injury. Main Outcomes and Measures: DALYs, years of life lost (YLL), and years lived with disability (YLD) were analyzed by hematoma location, ICH volume, and secondary injury (ie, hematoma expansion [HE], intraventricular hemorrhage [IVH], and perihemorrhagic edema [PHE]). Results: Among 1322 patients with ICH, 615 (46.5%) were women and the mean (SD) age at hospital admission was 71 (13) years; ICH was associated with a mean (SD) of 9.46 (8.08) DALYs, 5.72 (8.29) YLL, and 3.74 (5.95) YLD. There were statistically significant differences in mean (SD) DALYs by extent of hematoma volume (< 10 mL ICH: 7.05 [6.79] DALYs; 10-30 mL ICH: 9.91 [8.35] DALYs; >30 mL ICH: 12.42 [8.47] DALYs; P <.001) and ICH location (deep location: 10.60 [8.35] DALYs; lobar location: 8.18 [7.63] DALYs; cerebellum: 8.14 [6.80] DALYs; brainstem: 12.63 [9.21] DALYs; P <.001). Regarding population-level disease burden of secondary injuries after ICH, there was a statistically significant difference in mean (SD) by injury type, with 0.94 (3.19) DALYs for HE, 2.45 (4.16) DALYs for IVH, and 1.96 (2.66) DALYs for PHE (P <.001) among the entire ICH cohort. Regarding individual-level exposure to secondary injuries after ICH, there were a mean (SD) 7.14 (6.62) DALYs for HE, 4.58 (4.75) DALYs for IVH, and 3.35 (3.28) DALYs for PHE among patients with ICH affected by secondary injuries. Conclusions and Relevance: These findings suggest that there is a high burden of disability associated with ICH and secondary injuries, and the findings may guide public health strategies. The study findings further suggest that IVH and PHE may be relevant for the overall outcome of patients with ICH, that DALYs may represent a viable outcome parameter for studies to evaluate treatment outcomes in ICH research, and that IVH and PHE may represent potential treatment targets..
CRIS-Team Scopus Importer:2021-07-30

Disease Modeling of Neuropsychiatric Brain Disorders Using Human Stem Cell-Based Neural Models - Kaindl, Johanna; Winner, Beate (Behavioral Neurogenomics, 2019)
Human pluripotent stem (PS) cells are a relevant platform to model human-specific neurological disorders. In this chapter, we focus on human stem cell models for neuropsychiatric disorders including induced pluripotent stem (iPS) cell-derived neural precursor cells (NPCs), neurons and cerebral organoids. We discuss crucial steps for planning human disease modeling experiments. We introduce the different strategies of human disease modeling including transdifferentiation, human embryonic stem (ES) cell-based models, iPS cell-based models and genome editing options. Analysis of disease-relevant phenotypes is discussed. In more detail, we provide exemplary insight into modeling of the neurodevelopmental defects in autism spectrum disorder (ASD) and the process of neurodegeneration in Alzheimer's disease (AD). Besides monogenic diseases, iPS cell-derived models also generated data from idiopathic and sporadic cases.
CRIS-Team Scopus Importer:2019-12-24
Keywords: Disease modeling; hiPSC-derived neurons; hiPSCs; Neuropsychiatric disorders; Organoids

Disseminated Multifocal Intracerebral Bleeding Events in Three Coronavirus Disease 2019 Patients on Extracorporeal Membrane Oxygenation As Rescue Therapy. - Bihlmaier, Karl; Coras, Roland; Willam, Carsten; Grampp, Steffen; Jabari, Samir; Eichhorn, Philip; Haller, Florian; Kuramatsu, Joji; Schwab, Stefan; Castellanos, Ixchel; Birkholz, Torsten; Schüttler, Jürgen; et al. (Critical Care Explorations, 2020)
Objectives: To describe three coronavirus disease 2019 patients suffering from acute respiratory distress syndrome under venovenous extracorporeal membrane oxygenation therapy and tight anticoagulation monitoring presenting a novel pattern of multifocal brain hemorrhage in various degrees in all cerebral and cerebellar lobes. Design: Clinical observation of three patients. Post mortem examinations. Setting: Two ICUs at the University Hospital Erlangen. Patients: Three patients (medium age 56.6 yr, two male with hypertension and diabetes, one female with no medical history) developed severe acute respiratory distress syndrome on the basis of a severe acute respiratory syndrome coronavirus 2 infection. All required mechanical ventilation and venovenous extracorporeal membrane oxygenation support. Interventions: Clinical observation, CT, data extraction from electronic medical records, and post mortem examinations. Main Results: We report on an unusual multifocal bleeding pattern in the white matter in three cases with severe acute respiratory distress syndrome due to coronavirus disease 2019 undergoing venovenous extracorporeal membrane oxygenation therapy. Bleeding pattern with consecutive herniation was found in CT scans as well as in neuropathologic post mortem examinations. Frequency for this unusual brain hemorrhage in coronavirus disease 2019 patients with extracorporeal membrane oxygenation therapy at our hospital is currently 50%, whereas bleeding events in extracorporeal membrane oxygenation patients generally occur at 10-15%. Conclusions: Multifocality and high frequency of the unusual white matter hemorrhage pattern suggest a coherence to coronavirus disease 2019. Neuropathological analyses showed circumscribed thrombotic cerebrovascular occlusions, which eventually led to microvascular and later on macrovascular disseminated bleeding events. However, signs of cerebrovascular inflammation could not be detected. Polymerase chain reaction analyses of brain tissue or cerebrospinal fluid remained negative. Increased susceptibility for fatal bleeding events should be taken into consideration in terms of systemic anticoagulation strategies in coronavirus disease 2019.
EVALuna2:313697
Keywords: acute respiratory distress syndrome; cerebral microhemorrhage; coronavirus disease 2019; extracorporeal membrane oxygenation; intracerebral bleeding

Distinct Effects of Chronic Dopaminergic Stimulation on Hippocampal Neurogenesis and Striatal Doublecortin Expression in Adult Mice - Salvi, Rachele; Steigleder, Tobias; Schlachetzki, Johannes; Waldmann, Elisabeth; Schwab, Stefan; Winner, Beate; Winkler, Jürgen; Kohl, Zacharias (Frontiers in Neuroscience, 2016)
While adult neurogenesis is considered to be restricted to the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ), recent studies in humans and rodents provide evidence for newly generated neurons in regions generally considered as non-neurogenic, e.g., the striatum. Stimulating dopaminergic neurotransmission has the potential to enhance adult neurogenesis in the SVZ and the DG most likely via D2/D3 dopamine (DA) receptors. Here, we investigated the effect of two distinct preferential D2/D3 DA agonists, Pramipexole (PPX), and Ropinirole (ROP), on adult neurogenesis in the hippocampus and striatum of adult naïve mice. To determine newly generated cells in the DG incorporating 5-bromo-2'-deoxyuridine (BrdU) a proliferation paradigm was performed in which two BrdU injections (100 mg/kg) were applied intraperitoneally within 12 h after a 14-days-DA agonist treatment. Interestingly, PPX, but not ROP significantly enhanced the proliferation in the DG by 42% compared to phosphate buffered saline (PBS)-injected control mice. To analyze the proportion of newly generated cells differentiating into mature neurons, we quantified cells co-expressing BrdU and Neuronal Nuclei (NeuN) 32 days after the last of five BrdU injections (50 mg/kg) applied at the beginning of 14-days DA agonist or PBS administration. Again, PPX only enhanced neurogenesis in the DG significantly compared to ROP- and PBS-injected mice. Moreover, we explored the pro-neurogenic effect of both DA agonists in the striatum by quantifying neuroblasts expressing doublecortin (DCX) in the entire striatum, as well as in the dorsal and ventral sub-regions separately. We observed a significantly higher number of DCX(+) neuroblasts in the dorsal compared to the ventral sub-region of the striatum in PPX-injected mice. These results suggest that the stimulation of hippocampal and dorsal striatal neurogenesis may be up-regulated by PPX. The increased generation of neural cells, both in constitutively active and quiescent neurogenic niches, might be related to the proportional higher D3 receptor affinity of PPX, non-dopaminergic effects of PPX, or altered motor behavior.
EVALuna2:5538

Distinct forebrain regions define a dichotomous astrocytic profile in multiple system atrophy - Schneider, Yanni; Gauer, Carina; Andert, Marie; Hoffmann, Alana; Riemenschneider, M. J.; Krebs, W.; Chalmers, Nicholas; Lötzsch, C.; Naumann, Ulrike; Xiang, Wei; Rothhammer, Veit; Beckervordersandforth, Ruth; et al. (Acta Neuropathologica Communications, 2024)
The growing recognition of a dichotomous role of astrocytes in neurodegenerative processes has heightened the need for unraveling distinct astrocytic subtypes in neurological disorders. In multiple system atrophy (MSA), a rare, rapidly progressing atypical Parkinsonian disease characterized by increased astrocyte reactivity. However the specific contribution of astrocyte subtypes to neuropathology remains elusive. Hence, we first set out to profile glial fibrillary acidic protein levels in astrocytes across the human post mortem motor cortex, putamen, and substantia nigra of MSA patients and observed an overall profound astrocytic response. Matching the post mortem human findings, a similar astrocytic phenotype was present in a transgenic MSA mouse model. Notably, MSA mice exhibited a decreased expression of the glutamate transporter 1 and glutamate aspartate transporter in the basal ganglia, but not the motor cortex. We developed an optimized astrocyte isolation protocol based on magnetic-activated cell sorting via ATPase Na+/K+ transporting subunit beta 2 and profiled the transcriptomic landscape of striatal and cortical astrocytes in transgenic MSA mice. The gene expression profile of astrocytes in the motor cortex displayed an anti-inflammatory signature with increased oligodendroglial and pro-myelinogenic expression pattern. In contrast, striatal astrocytes were defined by elevated pro-inflammatory transcripts accompanied by dysregulated genes involved in homeostatic functions for lipid and calcium metabolism. These findings provide new insights into a region-dependent, dichotomous astrocytic response—potentially beneficial in the cortex and harmful in the striatum—in MSA suggesting a differential role of astrocytes in MSA-related neurodegenerative processes.
CRIS-Team Scopus Importer:2024-01-12

Distinct Pattern of Microgliosis in the Olfactory Bulb of Neurodegenerative Proteinopathies - Kohl, Zacharias; Schlachetzki, Johannes; Feldewerth, Judith; Hornauer, Philipp; Muench, Martina; Adame, Anthony; Riemenschneider, Markus J.; Winkler, Jürgen; Masliah, Eliezer (Neural Plasticity, 2017)
The olfactory bulb (OB) shows early neuropathological hallmarks in numerous neurodegenerative diseases, for example, in Alzheimer's disease (AD) and Parkinson's disease (PD). The glomerular and granular cell layer of the OB is characterized by preserved cellular plasticity in the adult brain. In turn, alterations of this cellular plasticity are related to neuroinflammation such as microglia activation, implicated in the pathogenesis of AD and PD, as well as frontotemporal lobe degeneration (FTLD). To determine microglia proliferation and activation we analyzed ionized calcium binding adaptor molecule 1 (Iba1) expressing microglia in the glomerular and granular cell layer, and the olfactory tract of the OB from patients with AD, PD dementia/dementia with Lewy bodies (PDD/DLB), and FTLD compared to age-matched controls. The number of Iba1 and CD68 positive microglia associated with enlarged amoeboid microglia was increased particularly in AD, to a lesser extent in FTLD and PDD/DLB as well, while the proportion of proliferating microglia was not altered. In addition, cells expressing the immature neuronal marker polysialylated neural cell adhesion molecule (PSA-NCAM) were increased in the glomerular layer of PDD/DLB and FTLD cases only. These findings provide novel and detailed insights into differential levels of microglia activation in the OB of neurodegenerative diseases.
EVALuna2:35932

DIVI-Recommendations on the infrastruture of adult intensive care units - Waydhas, Christian; Riessen, Reimer; Markewitz, Andreas; Hoffmann, Florian; Frey, Lorenz; Boettiger, Bernd W.; Brenner, Sebastian; Brenner, Thorsten; Deffner, Teresa; Deininger, Matthias Manfred; Janssens, Uwe; Kluge, Stefan; et al. (Medizinische Klinik - Intensivmedizin und Notfallmedizin, 2023)
This document on the Structure and Equipment for Intensive Care Units of the German Association for Intensive and Emergency Care (DIVI) aims at providing guidance and recommendations for the requirements of (infra)structure, personal, and organization of intensive care units. The recommendations are based on a systematic literature search and a formal consensus process from a group of multi-disciplinary and multiprofessional specialists from the DIVI. The recommendations comprise a 3-staged level of intensive care units, a 3-staged level of care with respect to severity of illness, the staffing requirement of physicians, nurses, physiotherapists, pharmacists, psychologists, and other specialists. Furthermore, proposals concerning the equipment and the construction of ICUs are supplied.
CRIS-Team WoS Importer:2023-05-26

DNA methylation-based classification of malformations of cortical development in the human brain - Jabari, Samir; Kobow, Katja; Pieper, Tom; Hartlieb, Till; Kudernatsch, Manfred; Polster, Tilman; Bien, Christian G.; Kalbhenn, Thilo; Simon, Matthias; Hamer, Hajo; Roessler, Karl; Feucht, Martha; et al. (Acta Neuropathologica, 2022)
Malformations of cortical development (MCD) comprise a broad spectrum of structural brain lesions frequently associated with epilepsy. Disease definition and diagnosis remain challenging and are often prone to arbitrary judgment. Molecular classification of histopathological entities may help rationalize the diagnostic process. We present a retrospective, multi-center analysis of genome-wide DNA methylation from human brain specimens obtained from epilepsy surgery using EPIC 850 K BeadChip arrays. A total of 308 samples were included in the study. In the reference cohort, 239 formalin-fixed and paraffin-embedded (FFPE) tissue samples were histopathologically classified as MCD, including 12 major subtype pathologies. They were compared to 15 FFPE samples from surgical non-MCD cortices and 11 FFPE samples from post-mortem non-epilepsy controls. We applied three different statistical approaches to decipher the DNA methylation pattern of histopathological MCD entities, i.e., pairwise comparison, machine learning, and deep learning algorithms. Our deep learning model, which represented a shallow neuronal network, achieved the highest level of accuracy. A test cohort of 43 independent surgical samples from different epilepsy centers was used to test the precision of our DNA methylation-based MCD classifier. All samples from the test cohort were accurately assigned to their disease classes by the algorithm. These data demonstrate DNA methylation-based MCD classification suitability across major histopathological entities amenable to epilepsy surgery and age groups and will help establish an integrated diagnostic classification scheme for epilepsy-associated MCD.
CRIS-Team Scopus Importer:2021-12-03
Keywords: Brain development; Cortical malformation; Deep learning; Epigenetic; Epilepsy

Do all patients in the epilepsy monitoring unit experience the same level of comfort? A quantitative exploratory secondary analysis - Egger-Rainer, Andrea; Hettegger, Sophie Martina; Feldner, Raphael; Arnold, Stephan; Bosselmann, Christian; Hamer, Hajo; Hengsberger, Anna; Lang, Johannes; Lorenzl, Stefan; Lerche, Holger; Noachtar, Soheyl; Pataraia, Ekaterina; et al. (Journal of Advanced Nursing, 2021)
Aims To find out which variables may be associated with comfort of patients in an epilepsy monitoring unit. Design Exploratory, quantitative study design. Methods Data were collected from October 2018 to November 2019 in Austria and Southern Germany. A total of 267 patients of 10 epilepsy centres completed the Epilepsy Monitoring Unit Comfort Questionnaire which is based on Kolcaba's General Comfort Questionnaire. Secondary data analysis were conducted by using descriptive statistics and an exploratory model building approach, including different linear regression models and several sensitivity analyses. Results Total comfort scores ranged from 83 to 235 points. Gender, occupation and centre turned out to be possible influential variables. On average, women had a total comfort score 4.69 points higher than men, and retired persons 28.2 points higher than high school students >= 18 years. Comfort scores of younger patients were lower than those of older patients. However, age did not show a statistically significant effect. The same could be observed in marital status and educational levels. Conclusion When implementing comfort measures, nurses must be aware of variables which could influence the intervention negatively. Especially, high school students >= 18 years should be supported by epilepsy specialist nurses, in order to reduce uncertainty, anxiety and discomfort. But, since the identified variables account only for a small proportion of the inter-individual variability in comfort scores, further studies are needed to find out additional relevant aspects and to examine centre-specific effects more closely. Impact Nurses ensure patient comfort during a hospital stay. However, there are variables that may impair the effectiveness of the nursing measures. Our study showed that the experience of comfort was highly individual and could be explained by sociodemographic variables only to a limited extent. Nurses must be aware that additional factors, such as the situation in the individual setting, may be relevant.
CRIS-Team WoS Importer:2021-12-03

Does participation in art classes influence performance on two different cognitive tasks? - Schindler, Manuel; Maihöfner, Christian; Bolwerk, Anne; Lang, Frieder (Aging & Mental Health, 2017)
OBJECTIVES: Effects of two mentally stimulating art interventions on processing speed and visuo-spatial cognition were compared in three samples. METHOD: In a randomized 10-week art intervention study with a pre-post follow-up design, 113 adults (27 healthy older adults with subjective memory complaints, 50 healthy older adults and 36 healthy younger adults) were randomly assigned to one of two groups: visual art production or cognitive art evaluation, where the participants either produced or evaluated art. ANOVAs with repeated measures were computed to observe effects on the Symbol-Digit Test, and the Stick Test. RESULTS: Significant Time effects were found with regard to processing speed and visuo-spatial cognition. Additionally, there was found a significant Time × Sample interaction for processing speed. The effects proved robust after testing for education and adding sex as additional factor. CONCLUSION: Mental stimulation by participation in art classes leads to an improvement of processing speed and visuo-spatial cognition. Further investigation is required to improve understanding of the potential impact of art intervention on cognitive abilities across adulthood.
EVALuna2:36362

Dopamine receptor activation promotes adult neurogenesis in an acute Parkinson model - Winner, Beate; Hagl, Christian; Klucken, Jochen; Aigner, Ludwig; Masliah, Eliezer; Winkler, Jürgen; et al. (Experimental Neurology, 2009)
Cell proliferation of neural progenitors in the subventricular zone (SVZ) of Parkinson disease (PD) patients and animal models is decreased. It was previously demonstrated that the neurotransmitter dopamine modulates cell proliferation in the embryonic brain. The aim of the present study was to analyze whether oral treatment with the dopamine receptor agonist pramipexole (PPX) modulates adult neurogenesis in the SVZ/olfactory bulb system in a dopaminergic lesion model. 6-Hydroxydopamine (6-OHDA) lesioned adult rats received either PPX (1.0 mg/kg) or PBS orally twice daily and bromodeoxyuridine (BrdU, a cell proliferation marker) for 10 days and were perfused immediately after treatment or 4 weeks after PPX withdrawal. Stereological analysis revealed a significant augmentation in SVZ proliferation by PPX. Consecutively, enhanced neuronal differentiation and more new neurons were present in the olfactory bulb 4 weeks after PPX withdrawal. In addition, dopaminergic neurogenesis was increased in the olfactory bulb after PPX treatment. Motor activity as assessed by using an open field paradigm was permanently increased even after long term PPX withdrawal. In addition, we demonstrate that D2 and D3 receptors are present on adult rat SVZ-derived neural progenitors in vitro, and PPX specifically increased mRNA levels of epidermal growth factor receptor (EGF-R) and paired box gene 6 (Pax6).Oral PPX treatment selectively increases adult neurogenesis in the SVZ-olfactory bulb system by increasing proliferation and cell survival of newly generated neurons. Analyzing the neurogenic fate decisions mediated by D2/D3 signaling pathways may lead to new avenues to induce neural repair in the adult brain. (C) 2009 Elsevier Inc. All rights reserved.
Keywords: Adult neurogenesis; Neural progenitor cells; Dopamine; Parkinson; Dopamine agonist; Pramipexole

Dopaminergic lesioning impairs adult hippocampal neurogenesis by distinct modification of α-synuclein - Schlachetzki, Johannes; Grimm, Thomas; Schlachetzki, Zinayida; Ben Abdallah, Nada M. B.; Ettle, Benjamin; Voehringer, Patrizia; Ferger, Boris; Winner, Beate; Nuber, Silke; Winkler, Jürgen (Journal of Neuroscience Research, 2016)
Nonmotor symptoms of cognitive and affective nature are present in premotor and motor stages of Parkinson's disease (PD). Neurogenesis, the generation of new neurons, persists throughout the mammalian life span in the hippocampal dentate gyrus. Adult hippocampal neurogenesis may be severely affected in the course of PD, accounting for some of the neuropsychiatric symptoms such as depression and cognitive impairment. Two important PD-related pathogenic factors have separately been attributed to contribute to both PD and adult hippocampal neurogenesis: dopamine depletion and accumulation of alpha-synuclein (alpha-syn). In the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model, altered neurogenesis has been linked merely to a reduced dopamine level. Here, we seek to determine whether a distinct endogenous alpha-syn expression pattern is associated, possibly contributing to the hippocampal neurogenic deficit. We observed a persistent reduction of striatal dopamine and a loss of tyrosine hydroxylase-expressing neurons in the substantia nigra pars compacta in contrast to a complete recovery of tyrosine hydroxylase-immunoreactive dopaminergic fibers within the striatum. However, dopamine levels in the hippocampus were significantly decreased. Survival of newly generated neurons was significantly reduced and paralleled by an accumulation of truncated, membrane-associated, insoluble alpha-syn within the hippocampus. Specifically, the presence of truncated alpha-syn species was accompanied by increased activity of calpain-1, a calcium-dependent protease. Our results further substantiate the broad effects of dopamine loss in PD-susceptible brain nuclei, gradually involved in the PD course. Our findings also indicate a detrimental synergistic interplay between dopamine depletion and posttranslational modification of alpha-syn, contributing to impaired hippocampal plasticity in PD. (C) 2015 Wiley Periodicals, Inc.
EVALuna2:25336
Keywords: MPTP; C-terminal-cleaved alpha-synuclein; calpain-1

Doppler pulsatility index in spontaneous intracerebral hemorrhage - Kiphuth, Ines C.; Huttner, Hagen; Dörfler, Arnd; Schwab, Stefan; Köhrmann, Martin (European neurology, 2013)
Background and Purpose: Elevated intracranial pressure (ICP) as a result of intracerebral hemorrhage (ICH) and perihematomal edema often leads to tissue shift, which can be identified in cross-sectional imaging and presents a known predictor of functional outcome. Pulsatility indices (PIs) of the intracranial arteries as measured by transcranial Doppler sonography (TCD) may serve as surrogate parameters for ICP. This study aims to investigate whether PI correlates with ICP and midline shift and serves as a reliable predictor of functional outcome in patients with ICH. Methods: Within a 1-year period between April 2009 and April 2010, 136 patients with acute spontaneous, supratentorial ICH were admitted to our tertiary care hospital. One-hundred and twenty-four patients fulfilled the inclusion criteria and were eligible for analysis. TCD and transcranial duplex sonography were performed on admission and at least once more during hospital stay. Functional outcome was assessed 6 months after discharge. Correlation analyses, logistic regression analyses and receiver operating characteristic curves were calculated. Results: One-hundred and twenty-four patients were included in the analysis. Six-month mortality amounted to 39.5%. The ICH score and PIs of the middle cerebral artery were independent predictors of outcome 6 months after discharge. Conclusions: Early PI monitoring by TCD correlated with ICP and may be used to predict the outcome after 6 months. Copyright © 2013 S. Karger AG, Basel.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Functional outcome; Intracerebral hemorrhage; Midline shift; Pulsatility index; Transcranial duplex sonography

Do we understand the pathophysiology of gastrointestinal symptoms in patients with 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 (2018)
EVALuna2:201958

Do We Walk Differently at Home? A Context-Aware Gait Analysis System in Continuous Real-World Environments - Roth, Nils; Wieland, Georg P.; Küderle, Arne; Ullrich, Martin; Gladow, Till; Marxreiter, Franz; Klucken, Jochen; Eskofier, Björn; Kluge, Felix (2021 43rd Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), 2021)
Driven by the advancements of wearable sensors and signal processing algorithms, studies on continuous real-world monitoring are of major interest in the field of clinical gait and motion analysis. While real-world studies enable a more detailed and realistic insight into various mobility parameters such as walking speed, confounding and environmental factors might skew those digital mobility outcomes (DMOs), making the interpretation of results challenging. To consider confounding factors, context information needs to be included in the analysis. In this work, we present a context-aware mobile gait analysis system that can distinguish between gait recorded at home and not at home based on Bluetooth proximity information. The system was evaluated on 9 healthy subjects and 6 Parkinsons disease (PD) patients. The classification of the at home/not at home context reached an average F1-score of 98.2 ± 3.2 %. A context-aware analysis of gait parameters revealed different walking bout length distributions between the two environmental conditions. Furthermore, a reduction of gait speed within the at home context compared to walking not at home of 8.9 ± 9.4 % and 8.7 ±5.9 % on average for healthy and PD subjects was found, respectively. Our results indicate the influence of the recording environment on DMOs and, therefore, emphasize the importance of context in the analysis of continuous motion data. Hence, the presented work contributes to a better understanding of confounding factors for future real-world studies.
Keywords: Legged locomotion; Bluetooth; Signal processing algorithms; Environmental factors; Biology; Motion analysis; Wearable sensors; Gait; Gait Analysis; Humans; Parkinsons Disease; Walking; Walking speed

Dressing Apraxia as Initial Manifestation of Creutzfeldt-Jakob Disease - Heckmann, Josef G.; Vachalova, Ivana; Vynogradova, Irina; Schwab, Stefan (Tremor and Other Hyperkinetic Movements, 2020)
Background: Creutzfeldt-Jakob disease (CJD) is a rare prion disease characterized by rapidly progressive dementia.
CRIS-Team WoS Importer:2020-07-24

Druggable transcriptomic pathways revealed in Parkinson’s patient-derived midbrain neurons - van den Hurk, Mark; Lau, Shong; Marchetto, Maria C.; Mertens, Jerome; Stern, Shani; Corti, Olga; Brice, Alexis; Winner, Beate; Winkler, Jürgen; Gage, Fred H.; Bardy, Cedric (npj Parkinson’s Disease, 2022)
Complex genetic predispositions accelerate the chronic degeneration of midbrain substantia nigra neurons in Parkinson’s disease (PD). Deciphering the human molecular makeup of PD pathophysiology can guide the discovery of therapeutics to slow the disease progression. However, insights from human postmortem brain studies only portray the latter stages of PD, and there is a lack of data surrounding molecular events preceding the neuronal loss in patients. We address this gap by identifying the gene dysregulation of live midbrain neurons reprogrammed in vitro from the skin cells of 42 individuals, including sporadic and familial PD patients and matched healthy controls. To minimize bias resulting from neuronal reprogramming and RNA-seq methods, we developed an analysis pipeline integrating PD transcriptomes from different RNA-seq datasets (unsorted and sorted bulk vs. single-cell and Patch-seq) and reprogramming strategies (induced pluripotency vs. direct conversion). This PD cohort’s transcriptome is enriched for human genes associated with known clinical phenotypes of PD, regulation of locomotion, bradykinesia and rigidity. Dysregulated gene expression emerges strongest in pathways underlying synaptic transmission, metabolism, intracellular trafficking, neural morphogenesis and cellular stress/immune responses. We confirmed a synaptic impairment with patch-clamping and identified pesticides and endoplasmic reticulum stressors as the most significant gene-chemical interactions in PD. Subsequently, we associated the PD transcriptomic profile with candidate pharmaceuticals in a large database and a registry of current clinical trials. This study highlights human transcriptomic pathways that can be targeted therapeutically before the irreversible neuronal loss. Furthermore, it demonstrates the preclinical relevance of unbiased large transcriptomic assays of reprogrammed patient neurons.
CRIS-Team Scopus Importer:2022-10-28

DSC Brain Perfusion Using Advanced Deconvolution Models in the Diagnostic Work-Up of Dementia and Mild Cognitive Impairment: A Semiquantitative Comparison with HMPAO-SPECT-Brain Perfusion - Schmidt, Manuel; Engelhorn, Tobias; Lang, Stefan; Lücking, Hannes; Hölter, Philip; Fröhlich, Kilian; Ritt, Philipp; Maler, Juan Manuel; Kuwert, Torsten; Kornhuber, Johannes; Dörfler, Arnd (Journal of Clinical Medicine, 2020)
Background: SPECT (single-photon emission-computed tomography) is used for the detection of hypoperfusion in cognitive impairment and dementia but is not widely available and related to radiation dose exposure. We compared the performance of DSC (dynamic susceptibility contrast) perfusion using semi- and fully adaptive deconvolution models to HMPAO-SPECT (99mTc-hexamethylpropyleneamine oxime-SPECT). Material and Methods: Twenty-seven patients with dementia of different subtypes including frontotemporal dementia (FTD) and mild cognitive impairment (MCI) received a multimodal diagnostic work-up including DSC perfusion at a clinical 3T high-field scanner and HMPAO-SPECT. Nineteen healthy control individuals received DSC perfusion. For calculation of the hemodynamic parameter maps, oscillation-index standard truncated singular value decomposition (oSVD, semi-adaptive) as well as Bayesian parameter estimation (BAY, fully adaptive) were performed. Results: Patients showed decreased cortical perfusion in the left frontal lobe compared to controls (relative cerebral blood volume corrected, rBVc: 0.37 vs. 0.27,p= 0.048, adjusted for age and sex). Performance of rBVc (corrected for T1 effects) was highest compared to SPECT for detection of frontal hypoperfusion (sensitivity 83%, specificity 80% for oSVD and BAY, area under curve (AUC) = 0.833 respectively,p< 0.05) in FTD and MCI. For nonleakage-corrected rBV and for rBF (relative cerebral blood flow), sensitivity of frontal hypoperfusion was above 80% for oSVD and for BAY (rBV: sensitivity 83%, specificity 75%, AUC = 0.908 for oSVD and 0.917 for BAY,p< 0.05 respectively; rBF: sensitivity 83%, specificity 65%, AUC = 0.825,p< 0.05 for oSVD). Conclusion: Advanced deconvolution DSC can reliably detect pathological perfusion alterations in FTD and MCI. Hence, this widely accessible technique has the potential to improve the diagnosis of dementia and MCI as part of an interdisciplinary multimodal imaging work-up. Advances in knowledge: Advanced DSC perfusion has a high potential in the work-up of suspected dementia and correlates with SPECT brain perfusion results in dementia and MCI.
CRIS-Team WoS Importer:2020-07-31

Dual-Center, Dual-Platform Microrna Profiling Identifies Plasma Biomarkers of Adult Temporal Lobe Epilepsy - Raoof, R.; Bauer, S.; El Naggar, H.; Brennan, G.; Hill, T.; Brindley, E.; Connolly, N.; Mcardle, H.; Spain, E.; Forster, R.; Prehn, J.; Hamer, Hajo; et al. (2018)
EVALuna2:201943

Dynamic footprint based locomotion sway assessment in α-synucleinopathic mice using Fast Fourier Transform and Low Pass Filter - Timotius, Ivanna; Canneva, Fabio; Minakaki, Georgia; Pasluosta, Cristian Federico; Moceri, Sandra; Casadei, Nicolas; Riess, Olaf; Winkler, Jürgen; Klucken, Jochen; von Hörsten, Stephan; Eskofier, Björn (Journal of Neuroscience Methods, 2018)
Background Sway is a crucial gait characteristic tightly correlated with the risk of falling in patients with Parkinson´s disease (PD). So far, the swaying pattern during locomotion has not been investigated in rodent models using the analysis of dynamic footprint recording obtained from the CatWalk gait recording and analysis system. New Methods We present three methods for describing locomotion sway and apply them to footprint recordings taken from C57BL6/N wild-type mice and two different α-synuclein transgenic PD-relevant mouse models (α-synm-ko, α-synm-koxα-synh-tg). Individual locomotion data were subjected to three different signal processing analytical approaches: the first two methods are based on Fast Fourier Transform (FFT), while the third method uses Low Pass Filters (LPF). These methods use the information associated with the locomotion sway and generate sway-related parameters. Results The three proposed methods were successfully applied to the footprint recordings taken from all paws as well as from front/hind-paws separately. Nine resulting sway-related parameters were generated and successfully applied to differentiate between the mouse models under study. Namely, α-synucleinopathic mice revealed higher sway and sway itself was significantly higher in the α-synm-koxα-synh-tg mice compared to their wild-type littermates in eight of the nine sway-related parameters. Comparison with Existing Method Previous locomotion sway index computation is based on the estimated center of mass position of mice. Conclusions The methods presented in this study provide a sway-related gait characterization. Their application is straightforward and may lead to the identification of gait pattern derived biomarkers in rodent models of P
EVALuna2:32788
Keywords: Locomotion; sway; gait analysis; CatWalk system; Parkinson's disease; alpha-synuclein transgenic

Dynamic footprints of α-synucleinopathic mice recorded by CatWalk gait analysis - Timotius, Ivanna; Canneva, Fabio; Minakaki, Georgia; Pasluosta, Cristian Federico; Moceri, Sandra; Casadei, Nicolas; Riess, Olaf; Winkler, Jürgen; Klucken, Jochen; von Hörsten, Stephan; Eskofier, Björn (Data in Brief, 2018)
Characterizing gait is important in the study of movement disorders, also in clinical mouse models. Gait data are therefore necessary for the development of gait analysis methods and the study of diseases. This article presents gait data of two α-synucleinopathic transgenic mouse models and their non-transgenic littermate, backcrossed into the C57BL/6N genetic background. The animal gait was recorded using CatWalk system, which provides the information for each run about the paw positions, paw print sizes, and paw intensities as a function of time or video frame. A total of 90 run data files are provided in this article.
Keywords: Data; gait analysis; CatWalk system; Parkinson's disease; alpha-synuclein transgenic.

Dysfunction of spatacsin leads to axonal pathology in SPG11-linked hereditary spastic paraplegia - Perez-Branguli, Francesc; Mishra, Himanshu Kumar; Prots, Iryna; Havlicek, Steven; Kohl, Zacharias; Saul, Domenica; Rummel, Christine; Dorca-Arevalo, Jonatan; Regensburger, Martin; Graef, Daniela; Sock, Elisabeth; Blasi, Juan; et al. (Human Molecular Genetics, 2014)
Hereditary spastic paraplegias are a group of inherited motor neuron diseases characterized by progressive paraparesis and spasticity. Mutations in the spastic paraplegia gene SPG11, encoding spatacsin, cause an autosomal-recessive disease trait; however, the precise knowledge about the role of spatacsin in neurons is very limited. We for the first time analyzed the expression and function of spatacsin in human forebrain neurons derived from human pluripotent stem cells including lines from two SPG11 patients and two controls. SPG11 patients'-derived neurons exhibited downregulation of specific axonal-related genes, decreased neurite complexity and accumulation of membranous bodies within axonal processes. Altogether, these data point towards axonal pathologies in human neurons with SPG11 mutations. To further corroborate spatacsin function, we investigated human pluripotent stem cell-derived neurons and mouse cortical neurons. In these cells, spatacsin was located in axons and dendrites. It colocalized with cytoskeletal and synaptic vesicle (SV) markers and was present in synaptosomes. Knockdown of spatacsin in mouse cortical neurons evidenced that the loss of function of spatacsin leads to axonal instability by downregulation of acetylated tubulin. Finally, time-lapse assays performed in SPG11 patients'-derived neurons and spatacsin-silenced mouse neurons highlighted a reduction in the anterograde vesicle trafficking indicative of impaired axonal transport. By employing SPG11 patient-derived forebrain neurons and mouse cortical neurons, this study provides the first evidence that SPG11 is implicated in axonal maintenance and cargo trafficking. Understanding the cellular functions of spatacsin will allow deciphering mechanisms of motor cortex dysfunction in autosomal-recessive hereditary spastic paraplegia.
EVALuna2:4956

Dysmorphic neurons as cellular source for phase-amplitude coupling in Focal Cortical Dysplasia Type II - Rampp, Stefan; Rössler, Karl; Hamer, Hajo; Illek, Margit; Buchfelder, Michael; Dörfler, Arnd; Pieper, Tom; Hartlieb, Till; Kudernatsch, Manfred; Kölble, Konrad; Peixoto-Santos, Jose Eduardo; Blümcke, Ingmar; et al. (Clinical Neurophysiology, 2021)
Objective: Reliable localization of the epileptogenic zone is necessary for successful epilepsy surgery. Neurophysiological biomarkers include ictal onsets and interictal spikes. Furthermore, the epileptic network shows oscillations with potential localization value and pathomechanistic implications. The cellular origin of such markers in invasive EEG in vivo remains to be clarified. Methods: In the presented pilot study, surgical brain samples and invasive EEG recordings of seven patients with surgically treated Focal Cortical Dysplasia (FCD) type II were coregistered using a novel protocol. Dysmorphic neurons and balloon cells were immunohistochemically quantified. Evaluated markers included seizure onset, spikes, and oscillatory activity in delta, theta, gamma and ripple frequency bands, as well as sample entropy and phase-amplitude coupling between delta, theta, alpha and beta phase and gamma amplitude. Results: Correlations between histopathology and neurophysiology provided evidence for a contribution of dysmorphic neurons to interictal spikes, fast gamma activity and ripples. Furthermore, seizure onset and phase-amplitude coupling in areas with dysmorphic neurons suggests preserved connectivity is related to seizure initiation. Balloon cells showed no association. Conclusions: Phase-amplitude coupling, spikes, fast gamma and ripples are related to the density of dysmorphic neurons and localize the seizure onset zone. Significance: The results of our pilot study provide a new powerful tool to address the cellular source of abnormal neurophysiology signals to leverage current and novel biomarkers for the localization of epileptic activity in the human brain.
CRIS-Team Scopus Importer:2021-02-19
Keywords: Electrophysiological markers; Epilepsy; Focal cortical dysplasia; Invasive EEG

Early Degeneration of Both Dopaminergic and Serotonergic Axons - A Common Mechanism in Parkinson's Disease - Grosch, Janina; Winkler, Jürgen; Kohl, Zacharias (Frontiers in Cellular Neuroscience, 2016)
Motor symptoms in Parkinson's disease (PD) are tightly linked to the degeneration of substantia nigra dopaminergic neurons and their projections into the striatum. Moreover, a broad range of non-motor symptoms like anxiety and depression frequently occur in PD, most likely related to the loss of serotonergic neurons and their projections into corresponding target regions. Strikingly, nigral dopaminergic neurons and raphe serotonergic neurons are severely affected in PD showing characteristic hallmarks of PD neuropathology, in particular alpha-synuclein containing Lewy bodies and Lewy neurites. So far, the initial events underlying neurodegenerative processes in PD are not well understood. Several observations, however, indicate that neurites and synapses of diseased neurons may be the first subcellular compartments compromised by alpha-synuclein associated pathology. In particular axonal pathology and deficits in axonal transport may be leading to the onset of synucleinopathies such as PD. This review will highlight current findings derived from imaging and neuropathological studies in PD patients, as well as cellular and animal PD models, which define the initial underlying structural and molecular events within dopaminergic and serotonergic circuits leading to the 'dying back' degeneration of axonal projections in PD.
EVALuna2:33511

Early Initiation of Anticoagulation with Direct Oral Anticoagulants in Patients after Transient Ischemic Attack or Ischemic Stroke - Macha, Kosmas; Volbers, Bastian; Bobinger, Tobias; Kurka, Natalia; Breuer, Lorenz; Huttner, Hagen; Schwab, Stefan; Köhrmann, Martin (Journal of Stroke and Cerebrovascular Diseases, 2016)
Direct oral anticoagulants (DOACs) are increasingly used for secondary prevention of cardioembolic stroke. While DOACs are associated with a long-term reduced risk of intracranial hemorrhage compared to vitamin K antagonists, pivotal trials avoided the very early period after stroke and few data exist on early initiation of DOAC therapy post stroke.We retrospectively analyzed data from our prospective database of all consecutive transient ischemic attack (TIA) or ischemic stroke patients with atrial fibrillation treated with DOACs during hospital stay. As per our institutional treatment algorithm for patients with cardioembolic ischemia DOACs are started immediately in TIA and minor stroke (group 1), within days 3-5 in patients with infarcts affecting one third or less of the middle cerebral artery, the anterior cerebral artery, or the posterior cerebral artery territories (group 2) as well as in infratentorial stroke (group 3) and after 1-2 weeks in patients with large infarcts (> 1/3 MCA territory, group 4). We investigated baseline characteristics, time to initiation of DOAC therapy after symptom onset, and hemorrhagic complications.In 243 included patients, administration of DOAC was initiated 40.5 hours (interquartile range [IQR] 23.0-65.5) after stroke onset in group 1 (n = 41) and after 76.7 hours (IQR 48.0-134.0), 108.4 hours (IQR 67.3-176.4), and 161.8 hours (IQR 153.9-593.8) in groups 2-4 (n = 170, 28, and 4), respectively. Two cases of asymptomatic intracranial hemorrhage (.8%) and 1 case of symptomatic intracranial hemorrhage (.4%) were observed, both in group 2.No severe safety issues were observed in early initiation of DOACs for secondary prevention after acute stroke in our in-patient cohort.
EVALuna2:22461

EARLY MANIFESTATION AND RAPID SYMPTOM PROGRESSION IN A CASE OF HOMOZYGOUS TRINUCLEOTIDE EXPANSION IN THE TBP-GENE IN AUTOSOMAL DOMINANT SPINOCEREBELLAR ATAXIA TYPE 17 - Forras, Patricia Vanda; Wilfling, Sibylle; Mrochen, Anne; Dufke, Claudia; Linker, Ralf; Hehr, Ute; Kohl, Zacharias (JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2022)
CRIS-Team WoS Importer:2022-12-23

Early postoperative tumor progression predicts clinical outcome in glioblastoma-implication for clinical trials - Merkel, Andreas; Soeldner, Dorothea; Wendl, Christina; Urkan, Dilek; Kuramatsu, Joji; Seliger, Corinna; Proescholdt, Martin; Eyupoglu, Ilker Y.; Hau, Peter; Uhl, Martin (Journal of Neuro-Oncology, 2017)
Molecular markers define the diagnosis of glioblastoma in the new WHO classification of 2016, challenging neuro-oncology centers to provide timely treatment initiation. The aim of this study was to determine whether a time delay to treatment initiation was accompanied by signs of early tumor progression in an MRI before the start of radiotherapy, and, if so, whether this influences the survival of glioblastoma patients. Images from 61 patients with early post-surgery MRI and a second MRI just before the start of radiotherapy were examined retrospectively for signs of early tumor progression. Survival information was analyzed using the Kaplan-Meier method, and a Cox multivariate analysis was performed to identify independent variables for survival prediction. 59 percent of patients showed signs of early tumor progression after a mean time of 24.1 days from the early post-surgery MRI to the start of radiotherapy. Compared to the group without signs of early tumor progression, which had a mean time of 23.3 days (p = 0.685, Student's t test), progression free survival was reduced from 320 to 185 days (HR 2.3; CI 95% 1.3-4.0; p = 0.0042, log-rank test) and overall survival from 778 to 329 days (HR 2.9; CI 95% 1.6-5.1; p = 0.0005). A multivariate Cox regression analysis revealed that the Karnofsky performance score, O-6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, and signs of early tumor progression are prognostic markers of overall survival. Early tumor progression at the start of radiotherapy is associated with a worse prognosis for glioblastoma patients. A standardized baseline MRI might allow for better patient stratification.
EVALuna2:22524

Early prediction of delayed cerebral ischemia in subarachnoid hemorrhage based on quantitative EEG: A prospective study in adults - Gollwitzer, S.; Groemer, Teja W.; Rampp, Stefan; Hagge, Mareike; Olmes, D.; Huttner, Hagen; Schwab, Sibylle; Madzar, D.; Hopfengaertner, R.; Hamer, Hajo (Clinical Neurophysiology, 2015)
Delayed cerebral infarction (DCI) has a significant impact on mortality and morbidity of patients with subarachnoid hemorrhage (SAH). The aim of this study was to define quantitative EEG (qEEG) parameters for the early and reliable prediction of DCI and compare the validity and time course of qEEG to standard procedures.12 consecutive unselected SAH patients (8 female, mean age 52 years, Hunt-and-Hess grade I-IV) were prospectively examined. Continuous six channel EEG monitoring was started within 48 h after admission (mean duration 5.2 days; range: 2-12 days). All raw and unselected EEG signal underwent automated artifact rejection, Short Time Fast Fourier Transformation and a detrending procedure in order to analyze regional spectral power changes in different frequency bands. According to clinical standards, transcranial Doppler sonography (TCD) was performed at least on alternate days and repeat cerebral computer tomography (CCT) as needed.6 patients (50%) developed vasospasm/DCI. Decrease of ?40% in power persisting over ?5h in the alpha band and ?6h in the theta band marked the optimal cut-off to detect DCI (sensitivity 89%, specificity 77% for alpha). EEG changes preceded detection of vasospasm/DCI in standard procedures by 2.3d ays. Changes in the beta and delta band as well as in the alpha/delta ratio demonstrated lower correlation with imminent DCI.Focal reduction in alpha power may represent a valid, observer independent, non-invasive and continuous marker for vasospasm/DCI in SAH patients.qEEG indicates imminent ischemia earlier than established diagnostic tools, such as TCD.
EVALuna2:22268

Early versus late start of direct oral anticoagulants after acute ischaemic stroke linked to atrial fibrillation: an observational study and individual patient data pooled analysis - De Marchis, Gian Marco; Seiffge, David J.; Schaedelin, Sabine; Wilson, Duncan; Caso, Valeria; Acciarresi, Monica; Tsivgoulis, Georgios; Koga, Masatoshi; Yoshimura, Sohei; Toyoda, Kazunori; Cappellari, Manuel; Bonetti, Bruno; et al. (Journal of Neurology Neurosurgery and Psychiatry, 2021)
Objective The optimal timing to start direct oral anticoagulants (DOACs) after an acute ischaemic stroke (AIS) related to atrial fibrillation (AF) remains unclear. We aimed to compare early (<= 5 days of AIS) versus late (>5 days of AIS) DOAC-start. Methods This is an individual patient data pooled analysis of eight prospective European and Japanese cohort studies. We included patients with AIS related to non-valvular AF where a DOAC was started within 30 days. Primary endpoints were 30-day rates of recurrent AIS and ICH. Results A total of 2550 patients were included. DOACs were started early in 1362 (53%) patients, late in 1188 (47%). During 212 patient-years, 37 patients had a recurrent AIS (1.5%), 16 (43%) before a DOAC was started; 6 patients (0.2%) had an ICH, all after DOAC-start. In the early DOAC-start group, 23 patients (1.7%) suffered from a recurrent AIS, while 2 patients (0.1%) had an ICH. In the late DOAC-start group, 14 patients (1.2%) suffered from a recurrent AIS; 4 patients (0.3%) suffered from ICH. In the propensity score-adjusted comparison of late versus early DOAC-start groups, there was no statistically significant difference in the hazard of recurrent AIS (aHR=1.2, 95% CI 0.5 to 2.9, p=0.69), ICH (aHR=6.0, 95% CI 0.6 to 56.3, p=0.12) or any stroke. Conclusions Our results do not corroborate concerns that an early DOAC-start might excessively increase the risk of ICH. The sevenfold higher risk of recurrent AIS than ICH suggests that an early DOAC-start might be reasonable, supporting enrolment into randomised trials comparing an early versus late DOAC-start.
CRIS-Team WoS Importer:2021-12-03

EARLY VERSUS LATE START OF DIRECT ORAL ANTICOAGULANTS AFTER AN ISCHEMIC STROKE LINKED TO ATRIAL FIBRILLATION - A MULTICENTER, PROPENSITY SCORE ADJUSTED ANALYSIS. - De Marchis, G. M.; Seiffge, D.; Schadelin, S.; Wilson, D.; Caso, V.; Acciarresi, M.; Tsivgoulis, G.; Koga, M.; Yoshimura, S.; Toyoda, K.; Cappellari, M.; Bonetti, B.; et al. (INTERNATIONAL JOURNAL OF STROKE, 2020)
CRIS-Team WoS Importer:2021-01-22

Economic burden of disease and mortality of intracranial haemorrhage under oral FXai: a German claims data analysis - Huttner, Hagen B.; Scherg, Felix; Kopke, Katarina; Schultze, Michael; Kossack, Nils; Gerner, Stefan T.; Kuramatsu, Joji; Schwab, Stefan (Neurological Research and Practice, 2025)
Background: Intracranial haemorrhage (ICH) is one of the most serious complications of anticoagulant therapy with oral factor Xa inhibitors (FXai). To meet an urgent medical need of optimising treatment pathways, we assessed the frequency of ICH during oral FXai treatment, as well as the associated burden on the German healthcare system. Methods: Our study was based on a claims database comprising over 4 million people with statutory health insurance in Germany. The study included people initiating oral FXai treatment for the first time between 2016 and 2021, and who experienced ICH during a three-year treatment period. For a balanced comparison of hospitalisations, costs, and mortality, propensity score matching between patients with and without ICH was performed. Results: During the study period, 78,086 patients had started oral FXai therapy, of which 530 experienced ICH during the therapy. The incidence rate of ICH was highest within the first 90 days after the start of oral FXai therapy during follow-up with 0.64 events per 100 patient-years (PY; 95% CI: 0.52–0.77%). Three-month mortality rates were significantly higher among patients who had experienced an ICH event (39.4%; 95% CI: 35.4–43.8%), as opposed to patients without ICH (5.9%; 95% CI: 4.2–8.3%). This difference prevailed during follow-up, while mortality increased at roughly equal rates in both patient groups. Patients with ICH were on average hospitalised for 40.4 days/PY (95% CI: 35.7 days – 45.2 days) in the first year after the event; comparable patients without ICH were hospitalised for 10.8 days/PY (95% CI: 8.3 days – 13.2 days). Annual total costs per patient were €37,328 (95% CI: €32,243–€42,412) for patients with ICH, and €10,564 (95% CI: €9,298–€11,831) for patients without ICH. Hospitalisation costs were the main driver with 86.1% versus 50.8%, respectively. Conclusions: Incidence rates of ICH during oral FXai therapy were within the range of other published real-world data. Duration of hospitalisations, associated costs, and mortality were high and significantly higher for patients with ICH than for comparable patients without ICH. The high burden on the healthcare system highlights the need for preventive measures and more efficient treatment pathways for patients with ICH under oral FXai therapy.
CRIS-Team Scopus Importer:2025-04-11
Keywords: Anticoagulation; Direct oral anticoagulant; DOAC; ICH; Intracranial haemorrhage; Oral factor Xa inhibitor; Oral FXai

Economic evaluation of Motor Neuron Diseases: a nationwide cross-sectional analysis in Germany - Heinrich, Felix; Cordts, Isabell; Günther, René; Stolte, Benjamin; Zeller, Daniel; Schröter, Carsten; Weyen, Ute; Regensburger, Martin; Wolf, Joachim; Schneider, Ilka; Hermann, Andreas; Metelmann, Moritz; et al. (Journal of Neurology, 2023)
Background and objectives: Motor Neuron Diseases (MND) are rare diseases but have a high impact on affected individuals and society. This study aims to perform an economic evaluation of MND in Germany. Methods: Primary patient-reported data were collected including individual impairment, the use of medical and non-medical resources, and self-rated Health-Related Quality of Life (HRQoL). Annual socio-economic costs per year as well as Quality-Adjusted Life Years (QALYs) were calculated. Results: 404 patients with a diagnosis of Amyotrophic Lateral Sclerosis (ALS), Spinal Muscular Atrophy (SMA) or Hereditary Spastic Paraplegia (HSP) were enrolled. Total annual costs per patient were estimated at 83,060€ in ALS, 206,856€ in SMA and 27,074€ in HSP. The main cost drivers were informal care (all MND) and disease-modifying treatments (SMA). Self-reported HRQoL was best in patients with HSP (mean EuroQoL Five Dimension Five Level (EQ-5D-5L) index value 0.67) and lowest in SMA patients (mean EQ-5D-5L index value 0.39). QALYs for patients with ALS were estimated to be 1.89 QALYs, 23.08 for patients with HSP and 14.97 for patients with SMA, respectively. Cost-utilities were estimated as follows: 138,960€/QALY for ALS, 525,033€/QALY for SMA, and 49,573€/QALY for HSP. The main predictors of the high cost of illness and low HRQoL were disease progression and loss of individual autonomy. Conclusion: As loss of individual autonomy was the main cost predictor, therapeutic and supportive measures to maintain this autonomy may contribute to reducing high personal burden and also long-term costs, e.g., care dependency and absenteeism from work.
CRIS-Team Scopus Importer:2023-07-07
Keywords: Cost of illness (COI); Cost-utilities; Health-related Quality of Life (HRQoL); Motor Neuron Disease (MND); Quality-adjusted life years (QALYs); Socio-economic burden

Eculizumab use in neuromyelitis optica spectrum disorders: real-world evidence from Germany and Austria - Ringelstein, M.; Asseyer, S.; Lindenblatt, G.; Fischer, K.; Pul, R.; Ozalp, S. -H.; Lohmann, L.; Giglhuber, K.; Haeussler, V.; Karenfort, M.; Hellwig, K.; Paul, F.; et al. (MULTIPLE SCLEROSIS JOURNAL, 2022)
CRIS-Team WoS Importer:2022-12-09

Eculizumab Use in Neuromyelitis Optica Spectrum Disorders Routine Clinical Care Data From a European Cohort - Ringelstein, Marius; Asseyer, Susanna; Lindenblatt, Gero; Fischer, Katinka; Pul, Refik; Skuljec, Jelena; Revie, Lisa; Giglhuber, Katrin; Häußler, Vivien; Karenfort, Michael; Hellwig, Kerstin; Paul, Friedemann; et al. (Neurology, 2024)
Background and Objectives Attack prevention is crucial in managing neuromyelitis optica spectrum disorders (NMOSDs). Eculizumab (ECU), an inhibitor of the terminal complement cascade, was highly effective in preventing attacks in a phase III trial of aquaporin-4 (AQP4)-IgG seropositive(+) NMOSDs. In this article, we evaluated effectiveness and safety of ECU in routine clinical care. Methods We retrospectively evaluated patients with AQP4-IgG+ NMOSD treated with ECU between December 2014 and April 2022 at 20 German and 1 Austrian university center(s) of the Neuromyelitis Optica Study Group (NEMOS) by chart review. Primary outcomes were effectiveness (assessed using annualized attack rate [AAR], MRI activity, and disability changes [Expanded Disability Status Scale EDSS]) and safety (including adverse events, mortality, and attacks after meningococcal vaccinations), analyzed by descriptive statistics. Results Fifty-two patients (87% female, age 55.0 ± 16.3 years) received ECU for 16.2 (interquartile range [IQR] 9.6 – 21.7) months. Forty-five patients (87%) received meningococcal vaccination before starting ECU, 9 with concomitant oral prednisone and 36 without. Seven of the latter (19%) experienced attacks shortly after vaccination (median: 9 days, IQR 6–10 days). No postvaccinal attack occurred in the 9 patients vaccinated while on oral prednisone before starting ECU and in 25 (re-)vaccinated while on ECU. During ECU therapy, 88% of patients were attack-free. The median AAR decreased from 1.0 (range 0–4) in the 2 years preceding ECU to 0 (range 0–0.8; p < 0.001). The EDSS score from start to the last follow-up was stable (median 6.0), and the proportion of patients with new T2-enhancing or gadolinium-enhancing MRI lesions in the brain and spinal cord decreased. Seven patients (13%) experienced serious infections. Five patients (10%; median age 53.7 years) died on ECU treatment (1 from myocardial infarction, 1 from ileus with secondary sepsis, and 3 from systemic infection, including 1 meningococcal sepsis), 4 were older than 60 years and severely disabled at ECU treatment start (EDSS score ≥ 7). The overall discontinuation rate was 19%. Discussion Eculizumab proved to be effective in preventing NMOSD attacks. An increased risk of attacks after meningococcal vaccination before ECU start and potentially fatal systemic infections during ECU—particularly in patients with comorbidities—must be considered. Further research is necessary to explore optimal timing for meningococcal vaccinations. Classification of Evidence This study provides Class IV evidence that eculizumab reduces annualized attack rates and new MRI lesions in AQP4-IgG+ patients with NMOSD.
CRIS-Team Scopus Importer:2024-10-25

Effectiveness of Lumbar Cerebrospinal Fluid Drain Among Patients With Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial. - Wolf, Stefan; Mielke, Dorothee; Barner, Christoph; Malinova, Vesna; Kerz, Thomas; Wostrack, Maria; Czorlich, Patrick; Salih, Farid; Engel, Doortje C.; Ehlert, Angelika; Staykov, Dimitre; Alturki, Abdulrahman Y.; et al. (JAMA Neurology, 2023)
IMPORTANCE: After aneurysmal subarachnoid hemorrhage, the use of lumbar drains has been suggested to decrease the incidence of delayed cerebral ischemia and improve long-term outcome. OBJECTIVE: To determine the effectiveness of early lumbar cerebrospinal fluid drainage added to standard of care in patients after aneurysmal subarachnoid hemorrhage. DESIGN, SETTING, AND PARTICIPANTS: The EARLYDRAIN trial was a pragmatic, multicenter, parallel-group, open-label randomized clinical trial with blinded end point evaluation conducted at 19 centers in Germany, Switzerland, and Canada. The first patient entered January 31, 2011, and the last on January 24, 2016, after 307 randomizations. Follow-up was completed July 2016. Query and retrieval of data on missing items in the case report forms was completed in September 2020. A total of 20 randomizations were invalid, the main reason being lack of informed consent. No participants meeting all inclusion and exclusion criteria were excluded from the intention-to-treat analysis. Exclusion of patients was only performed in per-protocol sensitivity analysis. A total of 287 adult patients with acute aneurysmal subarachnoid hemorrhage of all clinical grades were analyzable. Aneurysm treatment with clipping or coiling was performed within 48 hours. INTERVENTION: A total of 144 patients were randomized to receive an additional lumbar drain after aneurysm treatment and 143 patients to standard of care only. Early lumbar drainage with 5 mL per hour was started within 72 hours of the subarachnoid hemorrhage. MAIN OUTCOMES AND MEASURES: Primary outcome was the rate of unfavorable outcome, defined as modified Rankin Scale score of 3 to 6 (range, 0 to 6), obtained by masked assessors 6 months after hemorrhage. RESULTS: Of 287 included patients, 197 (68.6%) were female, and the median (IQR) age was 55 (48-63) years. Lumbar drainage started at a median (IQR) of day 2 (1-2) after aneurysmal subarachnoid hemorrhage. At 6 months, 47 patients (32.6%) in the lumbar drain group and 64 patients (44.8%) in the standard of care group had an unfavorable neurological outcome (risk ratio, 0.73; 95% CI, 0.52 to 0.98; absolute risk difference, -0.12; 95% CI, -0.23 to -0.01; P = .04). Patients treated with a lumbar drain had fewer secondary infarctions at discharge (41 patients [28.5%] vs 57 patients [39.9%]; risk ratio, 0.71; 95% CI, 0.49 to 0.99; absolute risk difference, -0.11; 95% CI, -0.22 to 0; P = .04). CONCLUSION AND RELEVANCE: In this trial, prophylactic lumbar drainage after aneurysmal subarachnoid hemorrhage lessened the burden of secondary infarction and decreased the rate of unfavorable outcome at 6 months. These findings support the use of lumbar drains after aneurysmal subarachnoid hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01258257.
EVALuna2:536995

Effect of helium preconditioning on neurological decompression sickness in rats - Zhang, Rongjia; Yu, Yongchao; Manaenko, Anatol; Bi, Hongda; Zhang, Ning; Zhang, Ling; Zhang, Ting; Ye, Zhouheng; Sun, Xuejun (Journal of Applied Physiology, 2019)
Decompression sickness (DCS) occurs because of an excessively rapid and extensive reduction of the ambient pressure. Bubble-induced spinal cord ischemia is generally considered as a part of neurological DCS pathogenesis. Because helium preconditioning (HPC) recently demonstrated beneficial properties against ischemic damage, we hypothesized that HPC may decrease the neurological deficits of DCS in rats. Seventy-five male Sprague-Dawley rats were divided into a non-HPC group ( n = 25) and a HPC group ( n = 25) and 25 naive animals that were euthanized for histological examination ( n = 5) or anesthetized for baseline somatosensory evoked potential (SSEP) recordings ( n = 20). To induce DCS, rats were compressed with air to a pressure of 709 kPa for 60 min and decompressed at a rate of 203 kPa/min. HPC was administered as three episodes of 79% helium-21% oxygen mixture inhalation for 5 min interspersed with 5 min of air breathing. We found that HPC resulted in significantly decreased DCS incidence and delay of DCS onset. HPC also improved animal performance on the grip test after decompression and significantly ameliorated decompression-induced decrease of platelet number. Furthermore, the incidence of abnormal SSEP waves and histological spinal lesions was significantly reduced by HPC. We conclude that HPC can decrease the occurrence of DCS and ameliorate decompression-induced neurological deficits. NEW & NOTEWORTHY Helium preconditioning ameliorates decompression-induced neurological deficits in rats. Helium breathing before air dives may prevent neurological deficit and attenuate symptoms after decompression.
CRIS-Team Scopus Importer:2019-05-02
Keywords: decompression sickness; helium preconditioning; neurological deficit; somatosensory evoked potential; spinal cord injury