BackgroundRecent studies have reported that expanded GCA repeats in the GLS gene can cause glutaminase deficiency with ataxia phenotype. However, to data, no studies have investigated the distribution and role of GCA repeats in the GLS gene of Chinese individuals.ObjectiveThe aim was to investigate the distribution of GCA repeats in Chinese individuals, including undiagnosed ataxia patients for identifying

Backgroundα‐Synuclein seed amplification assay on cerebrospinal fluid (CSF‐αSyn‐SAA) has shown high accuracy for Parkinson's disease (PD) diagnosis. The analysis of CSF‐αSyn‐SAA parameters may provide useful insight to dissect the heterogeneity of synucleinopathies.ObjectiveTo assess differences in CSF‐αSyn‐SAA amplification parameters in participants with PD stratified by rapid eye movement (REM)

BackgroundTourette syndrome (TS) and chronic tic disorder (CTD) may be associated with an increased risk of mortality, but specific causes of death are poorly understood.ObjectivesIn this matched cohort and sibling cohort study, we estimated the risk of all‐cause and cause‐specific mortality in individuals with TS/CTD, compared with unaffected matched individuals and unaffected full siblings.MethodsWe

BackgroundThe various symptoms of Parkinson's disease (PD) may change differently over time as the disease progresses. Tremor usually manifests early in the disease, but unlike other motor symptoms, its severity may diminish over time. The cerebral mechanisms underlying these symptom‐specific longitudinal trajectories are unclear. Previous magnetic resonance imaging (MRI) studies have shown structural

BackgroundVPS13A disease is an ultra‐rare disorder caused by loss of function mutations in VPS13A characterized by striatal degeneration and by red blood cell (RBC) acanthocytosis. VPS13A is a bridge‐like protein mediating lipid transfer at membrane contact sites.ObjectivesTo assess the lipid composition of patient‐derived RBCs.MethodsRBCs collected from 5 VPS13A disease patients and 12 control subjects

BackgroundPatients with Parkinson's disease (PD) present progressive deterioration in both motor and non‐motor manifestations. However, the absence of clinical biomarkers for disease progression hinders clinicians from tailoring treatment strategies effectively.ObjectivesTo identify electroencephalography (EEG) biomarker that can track disease progression in PD.MethodsA total of 116 patients with PD

BackgroundA CAG repeat expansion in THAP11 was recently found to be associated with spinocerebellar ataxia in two Chinese families. Expanded repeats ranged from 45 to 100 units, with CAA sequence interruptions in the 5′ region and an uninterrupted CAG tract in the 3′ tail.ObjectiveHere, we assess the population distribution of the THAP11 repeat, and its contribution to neurological diseases.MethodsWe

BackgroundThe identification of a heterozygous exonic GGC repeat expansion in ZFHX3 underlying spinocerebellar ataxia type 4 (SCA4) has solved a 25‐year diagnostic conundrum. We used adaptive long‐read sequencing to decipher the pathogenic expansion in the index Utah family and an unrelated family from Iowa of Swedish ancestry. Contemporaneous to our discovery, other groups identified the same repeat

BACKGROUND Spasticity is a common feature in patients with disruptions in corticospinal pathways. However, the term is used ambiguously. Here, spasticity is defined as enhanced velocity-dependent stretch reflexes and placed within the context of deforming spastic paresis encompassing other forms of muscle overactivity. OBJECTIVE This scoping review aims at evaluating the clinimetric quality of clinical

BackgroundAdaptive deep brain stimulation (aDBS) dynamically adjusts stimulation parameters according to patient needs. We recently showed that chronic aDBS utilizing invasive neural signals for feedback control is superior to conventional DBS (cDBS) during normal daily life in a 2‐month trial. The stability of aDBS over longer periods remains unclear.ObjectivesTo assess the effects of aDBS on motor

BackgroundElectronic medical record (EMR)–based studies hold great potential for epidemiologic investigations of Parkinson's disease (PD) causal factors and phenomenology, but diagnostic misclassification may obscure or bias inferences.ObjectivesThe aims were to determine the validity of PD diagnostic codes in the Veterans Administration (VA) national electronic medical databases and develop recommendations

Intracerebral calcium deposition, classified into primary familial brain calcification (PFBC) and secondary brain calcification, occurs within the brain parenchyma and vasculature. PFBC manifests with progressive motor decline, dysarthria, and cognitive impairment, with limited treatment options available. Recent research has suggested a link between dysfunction of the blood–brain barrier (BBB) and

Spastic Paraplegia 4 (SPG4) is a debilitating neurodegenerative disorder characterized by progressive muscle weakness and spasticity in the lower limbs, often leading to gait impairment. Central to SPG4 pathology is the die‐back degeneration of corticospinal tracts, primarily driven by mutations in the spastin protein encoded by the SPAST gene. SPAST gives rise to two major spastin isoforms, M1‐ and

Outcomes derived from digital health technologies (DHTs) are promising candidate markers for monitoring Parkinson's disease (PD) progression. They have the potential to represent a significant shift in clinical research and therapeutic development in PD. However, their ability to track disease progression is yet to be established. This systematic review aimed to identify digital biomarkers capable

BackgroundRapid eye movement (REM) sleep behavior disorder (RBD) may precede motor symptoms in Parkinson's disease (PD) by years. According to a recent hypothesis, premotor RBD (pRBD) is a marker of the PD body‐first subtype, where synucleinopathy originates from the peripheral autonomic nervous system. Conversely, in the brain‐first subtype, pathology would arise in the brain. Functional connectivity

The age‐standardized prevalence of Parkinson's disease (PD) has increased substantially over the years and is expected to increase further. This emphasizes the need to identify modifiable risk factors of PD, which could form a logical entry point for the prevention of PD. The World Health Organization (WHO) has recommended reducing exposure to specific environmental factors that have been reported

Background and ObjectiveMemory impairment is a frequent and debilitating symptom in neurodegenerative disorders. The objective of this study was to provide proof‐of‐principle that deep brain stimulation during sleep can modify memory consolidation in people with Parkinson's disease depending on the stimulation frequency that is applied.MethodsTwenty‐four patients with Parkinson's disease who were treated

BackgroundThe pentanucleotide (TTTCA) repeat expansion (exp) insertion, along with the accompanying (TTTTA)exp, causes familial cortical myoclonic tremor with epilepsy (FCMTE). The genotype–phenotype correlations and intergenerational instabilities related to (TTTCA)exp and (TTTTA)exp are still unclear.ObjectiveThe aim was to investigate the genotype–phenotype correlations and intergenerational instabilities

BackgroundPopulation‐scale databases majorly contribute to variant interpretation. The recently released Genome Aggregation Database (gnomAD) v4 offers a >5‐fold increased sample size compared to v2.1.1. Pathogenic variants absent from v2.1.1 are now registered in v4 at a considerable rate. The implications on variant interpretation in dystonia are unknown.MethodsAll curated variants linked to the

BackgroundDepression is a common nonmotor complication in Parkinson's disease (PD). However, few studies have evaluated the efficacy of first‐line psychological therapies for depression in this patient population.ObjectivesThis randomized controlled trial evaluated the efficacy of interpersonal psychotherapy (IPT), an empirically validated intervention for depression that focuses on the bidirectional

BackgroundDeep brain stimulation is a treatment for advanced Parkinson's disease and currently tuned to target motor symptoms during daytime. Parkinson's disease is associated with multiple nocturnal symptoms such as akinesia, insomnia, and sleep fragmentation, which may require adjustments of stimulation during sleep for best treatment outcome.ObjectivesThere is a need for a robust biomarker to guide

BACKGROUND Dementia with Lewy bodies (DLB) commonly exhibits a complex neuropathology, sharing characteristics with Alzheimer's disease (AD), including tau aggregates. However, studies using the 18F-AV-1451 tau tracer have shown inconsistent findings regarding both the extent and topographical distribution of tau pathology in DLB. OBJECTIVES Our aim was to elucidate the topographical patterns of tau

BackgroundAlthough neuromelanin‐sensitive magnetic resonance imaging (NM‐MRI) has been used to evaluate early neurodegeneration in Parkinson's disease, studies concentrating on the locus coeruleus (LC) in pre‐dementia stages of dementia with Lewy bodies (DLB) are lacking.ObjectivesThe aims were to evaluate NM‐MRI signal changes in the LC in patients with mild cognitive impairment with Lewy bodies (MCI‐LB)

BackgroundAlterations in gut microbiota are observed in Parkinson's disease (PD). Previous studies on microbiota‐derived metabolites in PD were small‐scale and post‐diagnosis, raising concerns about reverse causality.ObjectivesOur goal was to prospectively investigate the association between plasma microbial metabolites and PD risk within a metabolomics framework.MethodsA nested case–control study

BackgroundSpinocerebellar ataxia type 3 (SCA3) is an autosomal dominant inherited neurodegenerative disorder for which there is currently no cure, nor effective treatment strategy.ObjectiveOur aim was to investigate the safety and efficacy of high‐dose ganglioside GM1 (ganglioside‐monosialic acid) pulse treatment in patients with SCA3.MethodsPatients were randomly allocated to receive either high‐dose

BackgroundThe age at onset (AAO) of Parkinson's disease (PD) varies widely among individuals and significantly influences disease progression and prognosis. However, few genome‐wide association studies (GWASs) have investigated genetic variants determining AAO, particularly in East Asian populations.ObjectivesTo identify single‐nucleotide polymorphisms (SNPs) affecting AAO of PD in Korean patients

BackgroundParkinson's disease (PD) is the second most common, and the fastest‐growing neurodegenerative disorder with unclear etiology in most cases. Therefore, the identification of non‐genetic risk factors for PD pathology is crucial to develop effective preventative or therapeutic strategies. An increasing number of evidence suggests that central insulin resistance might have an essential role in

BACKGROUND Chronic musculoskeletal pain often co-occurs with Parkinson's disease (PD); however, whether individuals with chronic pain have a higher risk of developing PD is unclear. OBJECTIVES To investigate the associations between chronic pain and incident risk of three neurodegenerative parkinsonism categories including PD, multiple system atrophy (MSA), and progressive supranuclear palsy (PSP)

BackgroundNo clinical trials have been reported on the use of focused ultrasound (FUS) for treating cervical dystonia.ObjectiveWe aimed to confirm the efficacy and safety of FUS pallidothalamic tractotomy for cervical dystonia.MethodsThis was a prospective, open‐label, non‐controlled pilot study. The primary outcome was defined as a change in the score for the Toronto Western Spasmodic Torticollis

BackgroundThe cerebellar cognitive affective syndrome (CCAS) encompasses cognitive and affective symptoms in patients with cerebellar disorders, for which no proven treatment is available.ObjectivesOur primary objective was to study the effect of cerebellar anodal transcranial direct current stimulation (tDCS) on cognitive performance in CCAS patients. Secondary effects on ataxia severity, mood, and

BackgroundHigh positivity rate of skin phosphorylated α‐synuclein (P‐SYN) was observed in Parkinson's disease (PD). Bullous pemphigoid (BP) is one of the most common autoimmune skin diseases associated with PD.ObjectivesOur aim was to investigate whether BP patients might be a targeted risk population for the screening of skin P‐SYN.MethodsSkin P‐SYN expression was evaluated by immunohistochemistry

BackgroundProgressive supranuclear palsy (PSP) is a rare and fatal neurodegenerative disorder for which there are currently no disease‐modifying treatments. Recent trials of potential therapies had durations of 12 months, which may be insufficient because of nonrandom missingness due to death. Longer durations, incorporating PSP Rating Scale and survival, can reduce the potential for type II error

BackgroundHereditary spastic paraplegia (HSP) is characterized by progressive lower limb weakness and spasticity, with unknown genetic cause in many cases.ObjectivesTo identify novel genetic causes of HSP.MethodsPhenotypic characterization, genetic screening, transcriptome sequencing, and peroneal nerve biopsy were conducted in a Chinese HSP family.ResultsWe found a homoplasmic MT‐TV (mitochondrial

Advances in genetic technologies and disease modeling have greatly accelerated the pace of introducing and validating molecular‐genetic contributors to disease. In dystonia, there is a growing convergence across multiple distinct forms of the disease onto core biological processes. Here, we discuss two of these, the endosome‐autophagosome‐lysosome pathway and the integrated stress response, to highlight

BackgroundThe p.Ser71Arg RAB32 variant was recently associated with Parkinson's disease (PD).ObjectiveThe aim was to investigate the presence of RAB32 variants in a large multiethnic group of individuals affected and unaffected by PD.MethodsWe queried our proprietary database that contains exome/genome sequencing data of >180,000 individuals. Additional PD patients were genotyped, and proximal p.Ser71Arg‐associated

BackgroundOrthostatic tremor (OT) is a rare movement disorder characterized by a feeling of unsteadiness and a high‐frequency tremor in the legs (13–18 Hz) relieved by sitting or walking.ObjectivesThe aims were to study the brain electrophysiology captured chronically in a person with medication‐refractory OT while standing and walking and in the semi‐recumbent position using bilateral ventral intermedius

BackgroundMotor and nonmotor fluctuations adversely impact the quality of life in Parkinson's disease (PD). Dysautonomia, a feature frequently associated with PD and a possible adverse effect of dopaminergic therapy, may be comorbid with fluctuations.ObjectiveWe sought to evaluate the effect of dysautonomia on motor and nonmotor fluctuations in PD.MethodsTwo hundred subjects with PD were evaluated

BackgroundIn Parkinson's disease (PD), postural instability and gait disorder (PIGD) symptoms are associated with a worse prognosis for an unknown reason.ObjectiveThe objective was to explore the relationship between cannabinoid receptor type 1 (CB1R) availability and motor symptoms in PD with [18F]FMPEP‐d2 positron emission tomography (PET).MethodsFifteen individuals with PD underwent [18F]FMPEP‐d2

BackgroundEfficacy of deep brain stimulation (DBS) relies on accurate lead placement as well as optimization of the stimulation parameters. Although clinical software tools are now available, programming still largely relies on a monopolar review, a tedious process for both patients and programmers.ObjectiveThis study investigates the safety and feasibility of prospective automated connectomic DBS