A5059290458- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Advanced MRI Techniques and Applications
- DNA Repair Mechanisms
- Advanced Neuroimaging Techniques and Applications
- Vestibular and auditory disorders
- Epilepsy research and treatment
- Fetal and Pediatric Neurological Disorders
- Dementia and Cognitive Impairment Research
- Visual perception and processing mechanisms
- Stuttering Research and Treatment
- Neurobiology of Language and Bilingualism
- Functional Brain Connectivity Studies
- Amyotrophic Lateral Sclerosis Research
- Neurological and metabolic disorders
- Neuroscience of respiration and sleep
- Hearing, Cochlea, Tinnitus, Genetics
- Alzheimer's disease research and treatments
- Neural dynamics and brain function
- Neonatal and fetal brain pathology
- Ultrasound and Hyperthermia Applications
- Health, Environment, Cognitive Aging
- Ultrasound Imaging and Elastography
German Center for Neurodegenerative Diseases
2016-2025
University Hospital Bonn
2016-2025
University of Bonn
2007-2025
Mayo Clinic in Arizona
2025
Max Delbrück Center
2024
Charité - Universitätsmedizin Berlin
2024
Ludwig-Maximilians-Universität München
2023
University Hospital Schleswig-Holstein
2023
University of Lübeck
2023
Medizinische Hochschule Hannover
2023
To delineate the full phenotypic spectrum, discriminative features, piloting longitudinal progression data, and sample size calculations of replication factor complex subunit 1 (RFC1) repeat expansions, recently identified as causing cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS).Multimodal RFC1 screening (PCR, Southern blot, whole-exome/genome sequencing-based approaches) combined with cross-sectional deep phenotyping in (1) cross-European cohort A (70 families) ≥2...
Abstract Ataxia due to an autosomal dominant intronic GAA repeat expansion in FGF14 [GAA-FGF14 ataxia, spinocerebellar ataxia 27B (SCA27B)] has recently been identified as one of the most common genetic late-onset ataxias. We here aimed characterize its phenotypic profile, natural history progression, and 4-aminopyridine (4-AP) treatment response. conducted a multi-modal cohort study 50 GAA-FGF14 patients, comprising in-depth phenotyping, cross-sectional longitudinal progression data (up 7...
The clinical heterogeneity of Alzheimer's disease is not reflected in the rather diffuse cortical deposition amyloid-β. We assessed relationship between symptoms, vivo tau pathology, amyloid distribution, and hypometabolism variants using novel multimodal PET imaging techniques. Tau pathology was primarily observed brain regions related to symptoms overlapped with areas hypometabolism. In contrast, amyloid-β diffusely distributed over entire cortex. may thus serve as a valuable biomarker for...
Article8 June 2020Open Access Source DataTransparent process Neurofilaments in spinocerebellar ataxia type 3: blood biomarkers at the preataxic and ataxic stage humans mice Carlo Wilke orcid.org/0000-0002-7250-8597 Hertie Institute for Clinical Brain Research (HIH), Center of Neurology, University Tübingen, Germany German Neurodegenerative Diseases (DZNE), Search more papers by this author Eva Haas Medical Genetics Applied Genomics, Centre Rare Diseases, Kathrin Reetz Department RWTH Aachen...
There is now robust evidence that the cerebellum-apart from its well-established role in motor control-is crucially involved a wide spectrum of cognitive and affective functions. Clinical neuropsychological studies together with anatomical advanced neuroimaging have yielded significant insights into specific features clinical relevance cerebellar involvement normal cognition mood.
Quantifying the volume of cerebellum and its lobes is profound interest in various neurodegenerative acquired diseases. Especially for most common spinocerebellar ataxias (SCA), which first antisense oligonculeotide-base gene silencing trial has recently started, there an urgent need quantitative, sensitive imaging markers at pre-symptomatic stages stratification treatment assessment. This work introduces CerebNet, a fully automated, extensively validated, deep learning method lobular...
Intronic GAA repeat expansions in the fibroblast growth factor 14 gene (
Abstract RFC1 disease, caused by biallelic repeat expansion in RFC1, is clinically heterogeneous terms of age onset, disease progression and phenotype. We investigated the role size influencing clinical variables disease. also assessed presence meiotic somatic instability repeat. In this study, we identified 553 patients carrying expansions measured 392 cases. Pearson’s coefficient was calculated to assess correlation between at onset. A Cox model with robust cluster standard errors adopted...
Abstract Background Given that new therapeutic options for spinocerebellar ataxias are on the horizon, there is a need markers reflect disease‐related alterations, in particular, preataxic stage, which clinical scales lacking sensitivity. Objective The objective of this study was to quantify regional brain volumes and upper cervical spinal cord areas ataxia type 3 vivo across entire time course disease. Methods We applied segmentation approach included lobular subsegmentation cerebellum...
ABSTRACT Background Clinical scales such as the Scale for Assessment and Rating of Ataxia (SARA) cannot be used to study ataxia at home or assess daily fluctuations. The objective current was develop a video‐based instrument, SARA , measuring severity easily independently home. Methods Based on feasibility self‐application, we selected 5 items (gait, stance, speech, nose‐finger test, fast alternating hand movements) (range, 0–28). We compared with total scores in 526 patients spinocerebellar...
Clinical trials in spinocerebellar ataxia type 3 (SCA3) will require biomarkers for use as outcome measures.To evaluate total tau (t-tau), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCHL1) and neurofilament light-chain (NfL) fluid SCA3, ATXN3 mutation carriers (n = 143) controls 172) were clinically assessed, the plasma concentrations of four proteins analysed on Simoa HD-1 platform. Eleven carrier cerebrospinal samples t-tau phosphorylated (p-tau181 )....
ABSTRACT Measures of step variability and body sway during gait have shown to correlate with clinical ataxia severity in several cross‐sectional studies. However, serve as a valid progression biomarker, these measures prove their sensitivity robustly capture longitudinal change, ideally within short time frames (eg, 1 year). We present the first multicenter analysis study spinocerebellar ataxias. performed combined (n = 28) (1‐year interval, n 17) Spinocerebellar Ataxia type 3 subjects...
Abstract Background Clinical trials for upcoming disease‐modifying therapies of spinocerebellar ataxias (SCA), a group rare movement disorders, lack endpoints sensitive to early disease progression, when therapeutics will be most effective. In addition, regulatory agencies emphasize the importance biological outcomes. Objectives READISCA, transatlantic clinical trial readiness consortium, investigated whether advanced multimodal magnetic resonance imaging (MRI) detects pathology progression...
Our objective was to evaluate the diagnostic performance of a convolutional neural network (CNN) trained on multiple MR imaging features lumbar spine, detect variety different degenerative changes spine. One hundred and forty-six consecutive patients underwent routine clinical MRI spine including T2-weighted were retrospectively analyzed using CNN for detection labeling vertebrae, disc segments, as well presence herniation, bulging, spinal canal stenosis, nerve root compression,...
This study was undertaken to identify magnetic resonance (MR) metrics that are most sensitive early changes in the brain spinocerebellar ataxia type 1 (SCA1) and 3 (SCA3) using an advanced multimodal MR imaging (MRI) protocol multisite trial setting.
<h3>Background and Objective:</h3> In spinocerebellar ataxia, ataxia onset can be preceded by mild clinical manifestation, cerebellar and/or brainstem alterations or biomarkers modifications. READISCA is a prospective, longitudinal observational study of patients with ataxias type 1 3 to provide essential markers for therapeutic interventions. We looked clinical, imaging biological that are present at an early-stage the disease. <h3>Methods:</h3> enrolled carriers pathological <i>ATXN1</i>...
Monitoring of disease severity is great importance for treatment and management clinical trials. The Scale Assessment Rating Ataxia (SARA) a frequently used, short easily applicable scale used to assess the ataxia. objective our study was develop training certification tool SARA. SARA scores were recorded according standardized protocol rated by three experts in consensus. Four hundred thirty-eight videos 67 patients included tool. tutorial section demonstrates complete examination on...