BackgroundHereditary ataxias are genetically diverse, yet up to 75% remain undiagnosed due to technological and financial barriers. The GGC repeat expansion in ZFHX3, responsible for spinocerebellar ataxia type 4 (SCA4), has only been described in individuals of Northern Europeandescent.ObjectiveUncover the genetic etiology of suspected hereditary movement disorders.MethodsWe performed Oxford Nanopore

BackgroundFunctional speech disorder (FND‐speech) is a subtype of functional neurological disorder, yet quantitative characterization of its motor and cognitive‐linguistic features remains underexplored.ObjectiveThis study aimed to quantitatively characterize FND‐speech by comparing acoustic and linguistic features in individuals with FND‐speech with healthy control subjects (HCs). The potential of

BackgroundIn some patients with parkinsonism and abnormal dopamine transporter (DAT) imaging using [123I]FP‐CIT single‐photon emission computed tomography (SPECT), subsequent clinical evolution does not fit well with a neurodegenerative diagnosis.ObjectiveThe objective was to analyze the results of positron emission tomography (PET) with the recently developed DAT radioligand [18F]FE‐PE2I in patients

BackgroundStimulation‐induced dyskinesias (SID) from deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) are uncommon; however, they are increasingly recognized. Once considered transient and indicative of effective neuromodulation, SID are now seen as potential therapy‐limiting side effects, akin to internal capsule activation. The mechanism and anatomical

BackgroundExcessive daytime sleepiness (EDS) is a disabling symptom of Lewy body disorders (LBD). The hypothalamus is a key sleep–wake regulator and is involved in Lewy pathology, but its contribution to EDS in LBD remains unclear.ObjectivesTo use diffusion‐weighted magnetic resonance imaging (MRI) to detect hypothalamic microstructure and determine its relationship to EDS symptoms in LBD in an exploratory

BackgroundParkinson disease (PD) disease‐modifying therapy (DMT) trials generally recruit individuals from teaching hospitals. Whether these participants represent the broader PD population is unclear.ObjectiveThe objective was to compare individuals with PD seen by neurologists in teaching hospitals early in their disease—a proxy for DMT trial‐eligible cohorts—with individuals seen in other settings

Neuroimaging with positron emission tomography (PET) has been instrumental in elucidating neurobiological mechanisms behind therapeutical trials in Parkinson's disease (PD). A variety of medical and neurosurgical interventions have been evaluated using many radioligands that reveal molecular basis for target engagement and brain responses in relation to clinical outcome measures. This review article

BackgroundPlasma phosphorylated tau181 (pTau181) is proving to be a useful predictor of Alzheimer's disease (AD). AD co‐pathology is frequently observed across the Lewy body disease (LBD) spectrum.ObjectiveTo determine whether pTau181 in LBD is associated with postmortem Alzheimer's disease neuropathologic changes (ADNC) and with antemortem positron emission spectrometry measurements of β‐amyloid and

BackgroundObject‐location memory impairment in Huntington's disease (HD) occurs from premanifest period and declines as HD progresses, however, pathogenesis of object‐location memory is unknown. The striatum and hippocampus are affected in HD, functionally interacting allowing intact object‐location memory.ObjectivesThe present study investigated if object location memory impairment in premanifest

BackgroundA previous case series showed that Nocebo Hypothesis Cognitive Behavioral Therapy (NH‐CBT) is a promising treatment for Functional Neurological Symptom Disorder (FNSD).ObjectivesTo further evaluate the potential efficacy of NH‐CBT in participants with FNSD (motor type).MethodsThis phase IIb pilot, randomized, parallel group trial compared the efficacy of NH‐CBT (n = 20) with an active control

BackgroundLower urinary tract symptoms (LUTS) are common Parkinson's disease (PD), causing great impact.ObjectiveThe goal was to undertake a phase II randomized control trial of transcutaneous tibial nerve stimulation (TTNS) delivered by Geko device for LUTS related to overactive bladder (OAB) in PD, an easy to use of the shelf solution.MethodsParticipants were randomized to active/sham stimulation

BackgroundParkinson's disease (PD) varies widely across individuals in clinical manifestations and course of progression. Identification of distinct biological subtypes could explain this heterogeneity, identify its pathophysiology, and predict disease progression.ObjectivesOur aim was to compare longitudinal clinical trajectories and brain atrophy patterns between clinical subtypes defined at the

BackgroundIn persons with Parkinson's disease (PD) and related disorders (PDRD), rates of end‐of‐life (EoL) hospitalization are greatest, and rates of hospice utilization lowest, among men and persons of color. Reasons for these differences are unknown.ObjectiveThe aim of this study was to determine whether attitudes toward EoL care differ by sex and race/ethnicity in persons with PDRD.MethodsIn this

BackgroundMultiple system atrophy (MSA) is a neurodegenerative disease pathologically characterized by the presence of glial cytoplasmic inclusions (GCI) composed of α‐synuclein aggregates. In Parkinson's disease, increases in monounsaturated fatty acids (MUFA) in phospholipid membranes promote α‐synuclein binding, aggregation, and toxicity, and the inhibition of stearoyl‐CoA desaturase (SCD), the

BackgroundCongenital mirror movement disorders (CMMs) are clinically and genetically heterogeneous in human patients. CMMs have not been documented to occur spontaneously in animals.ObjectiveThe objective of this work was to document the first case of CMMs spontaneously occurring in Weimaraner dogs and to identify the underlying genetic cause.MethodsClinical and pathological investigations were performed

BackgroundWith disease‐modifying drugs for degenerative ataxias on the horizon, ecologically valid measures of gait performance that can detect patient‐relevant changes in trial‐like time frames are highly warranted.ObjectivesIn this 2‐year longitudinal study, we aimed to unravel ataxic gait measures sensitive to longitudinal changes in patients' real lives using wearable sensors.MethodsWe assessed

BackgroundGlial cell line–derived neurotrophic factor (GDNF) is required for development and survival of dopaminergic neurons. A previous trial evaluating lower‐dose adeno‐associated virus serotype 2–GDNF (AAV2‐GDNF) bilateral intraputaminal infusion in participants with advanced Parkinson's disease (PD) achieved 26% mean putaminal coverage and was associated with stable motor features with no unexpected

BackgroundPrimary brain calcification (PBC) is a monogenic inherited disease characterized by calcifications in basal ganglia and other brain regions, with seven causative genes identified and highly heterogeneous genetic and phenotypic spectrum.ObjectiveThe objective was to update the genetic and phenotypic spectrum of PBC in a large cohort from China.MethodsFive hundred eighty‐four PBC families were

BackgroundParkinson's disease (PD) is the most common neurodegenerative movement disorder and one of the world's fastest‐growing neurological diseases. Although the exact causes of PD are unknown, mitochondrial dysfunction and inflammation may have significant roles in disease progression. As well as being prevalent in the brain, there is also evidence that peripheral mitochondrial dysfunction and

BackgroundAlpha‐synuclein‐related neurodegeneration affects sleep figures, whether in the prodromal (rapid eye movement [REM] sleep behavior disorder, iRBD) or established (Parkinson's disease [PD] and multiple system atrophy [MSA]) stages.ObjectiveTo look for abnormal intrusions of REMs in non‐REM sleep in alpha‐synucleinopathies.MethodsClinical measures and polysomnography were collected from 554

BackgroundLaryngeal dystonia (LD) is an isolated focal dystonia causing involuntary spasms in the laryngeal muscles that selectively impair speech production. LD is characterized as a functional and structural neural network disorder; however, the mechanistic aspects of network dysfunction in dystonia remain unknown.ObjectiveWe hypothesized that iron‐induced abnormal metabolic processes may underlie

BackgroundParkinsonism in infancy is rare and is highly correlated with the presence of dystonia. Advances in treating and characterizing developmental and infantile degenerative parkinsonism have highlighted the need for a specialized assessment scale.ObjectiveThe aim of this study was to design and validate a scale that effectively assesses parkinsonism‐dystonia in early life.MethodsThe Infantile

Atypical parkinsonian syndromes (APs) are characterized by parkinsonian features combined with additional motor and non‐motor signs and symptoms. Neurophysiological studies have contributed to clarifying differences and similarities between APs and idiopathic Parkinson's disease (PD) and to unravel specific pathophysiological features of APs. A comprehensive and updated evaluation of the potential

BackgroundParkinson's disease (PD) results from complex interactions among environmental, genetic, and aging factors. Telomeres, which ensure chromosome stability, naturally shorten with cell division, contributing to aging and cellular senescence. However, studies investigating telomere length (TL) in PD have produced inconsistent results.ObjectiveThis study aims to explore the relationship between

Dystonia is a movement disorder with varied clinical features and diverse etiologies. Here we present a revision of the 2013 consensus definition and classification of dystonia in light of subsequent publications and experience with its application during the last decade. A panel of movement disorder specialists with expertise in dystonia reviewed the original document and proposed some revision. There

BackgroundThe genetic landscape of pediatric cerebellar disorders (PCDs) in Finland is undefined.ObjectivesThe objective was to define epidemiological, clinical, neuroradiological, and genetic characteristics of PCDs in Northern Finland.MethodsA longitudinal population‐based cohort study of children with a movement disorder or a cerebellar malformation (diagnosis ≤16 years; study period 1970–2022)

BackgroundIn the 1920s, Jules Froment extensively studied conditions that might exacerbate rigidity in persons with Parkinson's disease (PD).ObjectiveThis cross‐sectional, controlled study aimed at investigating the physiological basis, in particular motor cortical contribution to enhanced rigidity during contralateral extremity movements.MethodsMotor‐evoked potentials (MEPs) were recorded in 42 patients

BackgroundHigh‐frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves Parkinson's disease (PD) motor symptoms but may deteriorate verbal fluency (VF). Theta stimulation showed potential cognitive benefits associated with motor worsening.ObjectivesThis randomized, double‐blind, crossover study evaluated the efficacy and safety of combined theta‐gamma frequency stimulation on

BackgroundDifferentiating progressive supranuclear palsy (PSP) from other parkinsonian disorders may be challenging.ObjectivesTo investigate the role of transforming growth factor beta‐1 (TGFβ1) in PSP.MethodsA total of 33 PSP, 39 Parkinson's disease (PD), 8 multiple system atrophy (MSA) patients, and 50 healthy controls (HC) were enrolled. TGFβ1 levels, including both active and inactive forms (latency‐associated

BackgroundThe efficacy and adverse events (AEs) of bilateral magnetic resonance‐guided focused ultrasound (MRgFUS) thalamotomies for essential tremor (ET) have not been compared to those of deep brain stimulation (DBS). Furthermore, it is uncertain whether second‐side thalamotomies can be positioned differently from the first without compromising effectiveness.ObjectiveWe aimed to indirectly compare

BACKGROUND Neuronal α-synuclein disease (NSD) is defined by the presence of an in vivo biomarker of neuronal alpha-synuclein (n-asyn) pathology. The NSD integrated staging system (NSD-ISS) for research describes progression across the disease continuum as stages 0 to 6. OBJECTIVE The aim was to assess 5-year longitudinal change in NSD-ISS in early disease. METHODS Analysis included a subset of participants

BackgroundDeep brain stimulation (DBS) elicits oscillatory local field potentials in patients with Parkinson's disease (PD) and other movement disorders. Greater knowledge about the fast dynamics of these neural responses could shed light on circuit pathophysiology and inform novel approaches to neuromodulation therapies.ObjectivesTo compare short‐term neuroplasticity in the globus pallidus interna

The evolution of the corticospinal tract (CST) is closely linked to the development of skilled voluntary movements in mammals. The main evolutionary divergence concerns the position of the CST within the spinal cord white matter and its postsynaptic targets in the grey matter. Here, we examine the developmental steps contributing to the CST projection pattern from an evolutionary point of view. Recent

BackgroundDefects of mitochondrial ATP synthase (ATPase) represent an emerging, yet incompletely understood group of neurodevelopmental diseases with abnormal movements.ObjectiveThe aim of this study was to redefine the phenotypic and mutational spectrum of movement disorders linked to the ATPase subunit‐encoding genes ATP5F1A and ATP5F1B.MethodsWe recruited regionally distant patients who had been

Long‐read sequencing methodologies provide powerful capacity to identify all types of genomic variations in a single test. Long‐read platforms such as Oxford Nanopore and PacBio have the potential to revolutionize molecular diagnostics by reaching unparalleled accuracies in genetic discovery and long‐range phasing. In the field of dystonia, promising results have come from recent pilot studies showing

Knowledge of the genetic factors in normal pressure hydrocephalus (NPH) is rapidly evolving, with significant advances in recent years. We conducted a systematic review examining genetic contributions to NPH risk. Ovid Embase, Ovid Medline, Web of Science, and Cochrane Central were searched from inception through October 14, 2024, for human studies in English reporting familial NPH cases, genetic variants

BackgroundFatigue in Parkinson's disease (PD) is a prevalent and debilitating non‐motor symptom. Despite its significant impact on quality of life, the underlying neurochemical and network‐based mechanisms remain poorly understood.ObjectivesThis observational study applied a multimodal imaging approach to explore potential links between the functional connectivity of neurotransmitter‐specific circuits

BackgroundThe Movement Disorder Society Non‐Motor Rating Scale (MDS‐NMS) assesses severity and frequency of non‐motor symptoms (NMS) in Parkinson's disease (PD) and is rater‐administered. The MDS‐NMS Questionnaire (MDS‐NMS‐Q), developed as a briefer (i.e., assessing symptom severity only), self‐completed version of the MDS‐NMS, is also a 13‐domain, 52‐symptom instrument with a separate non‐motor fluctuations

BackgroundIndividual variability in clinical response to dopamine replacement therapy (DRT) is a key barrier to efficacious treatment for patients with Parkinson's disease (PD). A better understanding of the neurobiological sources of such interindividual differences is necessary to personalize DRT prescribing, inform future clinical interventions, and motivate translational research.ObjectiveOne potential

BACKGROUND There are currently no disease-modifying therapies (DMTs) registered for Parkinson's disease (PD). The Edmond J. Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative will expedite clinical assessment of putative DMTs through a multi-arm multistage (MAMS) trial, testing several treatments against a common placebo arm and replacing unsuccessful therapies early. OBJECTIVE