A5082051712- Neurological disorders and treatments
- Genetic Neurodegenerative Diseases
- Neurological diseases and metabolism
- Parkinson's Disease Mechanisms and Treatments
- Metabolism and Genetic Disorders
- Botulinum Toxin and Related Neurological Disorders
- Glycogen Storage Diseases and Myoclonus
- Neurological and metabolic disorders
- Porphyrin Metabolism and Disorders
- Lysosomal Storage Disorders Research
- Hereditary Neurological Disorders
- Genetics and Neurodevelopmental Disorders
- Mitochondrial Function and Pathology
- Autoimmune Neurological Disorders and Treatments
- Economic and Social Issues
- RNA regulation and disease
- Congenital Heart Disease Studies
- Biochemical and Molecular Research
- Health and Medical Studies
- Epilepsy research and treatment
- Public Administration and Political Analysis
- Economic and Business Studies
- Medical and Health Sciences Research
- Transcranial Magnetic Stimulation Studies
- Neurogenetic and Muscular Disorders Research
University College London
2008-2024
Ludwig-Maximilians-Universität München
2014-2024
LMU Klinikum
2021-2024
Royal Free London NHS Foundation Trust
2024
General University Hospital in Prague
2024
Royal Manchester Children's Hospital
2024
Comenius University Bratislava
2024
Klinik und Poliklinik für Neurologie
2023
University of Duisburg-Essen
2022
Essen University Hospital
2022
Although many recessive loci causing parkinsonism dystonia have been identified, these do not explain all cases of the disorder.We used homozygosity mapping and mutational analysis in three individuals from two unrelated families who presented with adult-onset levodopa-responsive dystonia-parkinsonism, pyramidal signs cognitive/psychiatric features, cerebral cerebellar atrophy on magnetic resonance imaging but absent iron basal ganglia.We identified areas chromosome 22 and, subsequently,...
Voltage-gated potassium channel complex antibodies, particularly those directed against leucine-rich glioma inactivated 1, are associated with a common form of limbic encephalitis that presents cognitive impairment and seizures. Faciobrachial dystonic seizures have recently been reported as immunotherapy-responsive, brief, frequent events often predate the this encephalitis. However, these observations were made from retrospective study without serial assessments. Here, we undertook first...
Paroxysmal dyskinesias are episodic movement disorders that can be inherited or sporadic in nature. The pathophysiology underlying these remains largely unknown but may involve disrupted ion homeostasis due to defects cell-surface channels nutrient transporters. In this study, we describe a family with paroxysmal exertion-induced dyskinesia (PED) over 3 generations. Their PED was accompanied by epilepsy, mild developmental delay, reduced CSF glucose levels, hemolytic anemia echinocytosis,...
In this study, we combined linkage analysis with whole-exome sequencing of two individuals to identify candidate causal variants in a moderately-sized UK kindred exhibiting autosomal-dominant inheritance craniocervical dystonia. Subsequent screening these large number familial and sporadic cases cervical dystonia led the identification total six putatively pathogenic mutations ANO3, gene encoding predicted Ca2+-gated chloride channel that show be highly expressed striatum. Functional studies...
Neuronal ceroid lipofuscinoses (NCLs) comprise a heterogeneous group of metabolic storage diseases that present with the accumulation autofluorescent lipopigment, neurodegeneration and premature death. Nine genes have been thus far identified as cause different types NCL, ages at onset ranging from around birth to adult, although underlying etiology disease still remains elusive. We family typical NCL pathology in which we performed exome sequencing single homozygous mutation ATP13A2 fully...
Parkinson's disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization investigate over 3,000 genes encode druggable proteins predict their efficacy as targets for disease. expression protein quantitative trait loci mimic exposure medications, we examine the causal effect on risk (in two large cohorts), age at onset progression. propose 23...
Niemann-Pick disease type C is a rare lysosomal storage disorder. We evaluated the safety and efficacy of
Abstract We present the clinical details and dopamine transporter SPECT scan results of 10 patients with arm tremor, including a rest component reduced swing on affected side, in whom possibility PD had been raised. All signs dystonia or components their tremor that were compatible dystonic none true akinesia fatiguing decrement, even after mean follow‐up period 5.8 years. normal scans. Clinicians should be aware primary adult‐onset can an asymmetric resting impaired sometimes also facial...
Approximately 10% of patients diagnosed clinically with early Parkinson's disease (PD) have normal dopaminergic functional imaging (Scans Without Evidence Dopaminergic Deficit [SWEDDs]). An important subgroup SWEDDs are those asymmetric rest tremor resembling parkinsonian tremor. Clinical and pathophysiological features which could help to distinguish from PD not been explored. We therefore studied clinical details including non-motor symptoms in 25 tremulous comparison tremor-dominant...
Abstract Seven autosomal recessive genes associated with juvenile and young‐onset Levodopa‐responsive parkinsonism have been identified. Mutations in PRKN , DJ‐1 PINK1 are a rather pure parkinsonian phenotype, more benign course sustained treatment response absence of dementia. On the other hand, Kufor‐Rakeb syndrome has additional signs, which distinguish it clearly from Parkinson's disease including supranuclear vertical gaze palsy, myoclonic jerks, pyramidal cognitive impairment....
The 2 major types of neurodegeneration with brain iron accumulation (NBIA) are the pantothenate kinase type (PANK2)-associated (PKAN) and NBIA2 or infantile neuroaxonal dystrophy (INAD) due to mutations in phospholipase A2, group VI (PLA2G6) gene. We have recently demonstrated clinical heterogeneity patients PLA2G6 gene by identifying a poorly defined subgroup who present late dystonia parkinsonism. report genetic features 7 cases mutations. Brain was available 5 an age death ranging from 8...
Dystonia is characterized by two main pathophysiological abnormalities: 'reduced' excitability of inhibitory systems at many levels the sensorimotor system, and 'increased' plasticity neural connections in circuits a brainstem spinal level. A surprising finding recent papers has been fact that abnormalities inhibition similar to those organic dystonia are also seen patients who have psychogenic dystonia. To try determine critical feature might separate conditions, we investigated cortical...
Kufor Rakeb disease (KRD, PARK9) is an autosomal recessive extrapyramidal-pyramidal syndrome with generalized brain atrophy due to ATP13A2 gene mutations. We report clinical details and investigational results focusing on radiological findings of a genetically-proven KRD case. Clinically, there was early onset levodopa-responsive dystonia-parkinsonism pyramidal signs eye movement abnormalities. Brain MRI revealed putaminal caudate iron accumulation bilaterally. Our add the group syndromes...
The proline-rich transmembrane protein (PRRT2) gene was recently identified using exome sequencing as the cause of autosomal dominant paroxysmal kinesigenic dyskinesia (PKD) with or without infantile convulsions (IC) (PKD/IC syndrome). Episodic neurologic disorders, such epilepsy, migraine, and movement often coexist are thought to have a shared channel-related etiology. To investigate further frequency, spectrum, phenotype PRRT2 mutations, we analyzed this in 3 large series episodic...
Levodopa induced dyskinesias (LID) are a common problem which ultimately limit the effective treatment of patients with Parkinson's disease (PD). There is accumulating evidence that LID develop due to abnormal synaptic plasticity, in turn influenced by release brain derived neurotrophic factor (BDNF).The influence functional polymorphism BDNF gene on risk developing large cohort PD (n = 315), who were independently and variably treated levodopa and/or other dopaminergic treatments, was...
Deep brain stimulation of the internal pallidum (GPi-DBS) is an established therapeutic option in treatment-refractory dystonia, and identification factors predicting surgical outcome needed to optimize patient selection.
Our understanding of the syndromes Neurodegeneration with Brain Iron Accumulation (NBIA) continues to grow considerably. In addition core pantothenate kinase-associated neurodegeneration (PKAN, NBIA1) and PLA2G6-associated (PLAN, NBIA2), several other genetic causes have been identified (including FA2H, C19orf12, ATP13A2, CP FTL). parallel, clinical pathological spectrum has broadened new age-dependent presentations are being described. There is also growing recognition overlap between...