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

BACKGROUND Primary 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. OBJECTIVE The objective was to update the genetic and phenotypic spectrum of PBC in a large cohort from China. METHODS Five hundred eighty-four PBC families

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

BackgroundMagnetic resonance‐guided focused ultrasound (MRgFUS) is an established surgical treatment for essential tremor, providing tremor relief without the need for an incision or general anesthesia. Meta‐analyses have been limited in their exploration of the durability of the treatment effect.ObjectivesThe study aimed to assess the treatment effect and safety of this procedure over time. Different

BACKGROUND Lower urinary tract symptoms (LUTS) are common Parkinson's disease (PD), causing great impact. OBJECTIVE The 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. METHODS Participants were randomized to active/sham stimulation

BackgroundEssential tremor (ET) is one of the most prevalent movement disorders. However, the complete understanding of ET pathophysiology remains elusive.ObjectiveTo explore the pathophysiological role of primary motor cortex (M1) in ET, specifically exploring its neurophysiological changes and their correlation with voluntary motor abnormalities.MethodsWe recruited 30 ET patients and 18 healthy controls

BackgroundSpinocerebellar ataxia 27A (SCA27A) is a rare neurodegenerative disorder characterized by childhood‐onset tremor and progressive cerebellar dysfunction. SCA27A is usually caused by loss‐of‐function FGF14 variants.ObjectivesWe report the identification of a novel FGF14 variant in a five‐generation family with autosomal dominant ataxia and describe the clinical phenotype and response to subthalamic

BackgroundFreezing of gait (FoG) is a debilitating mobility disturbance that becomes increasingly resistant to dopaminergic pharmacotherapies with advancing Parkinson's disease (PD). The pathophysiology underlying the response of FoG to dopaminergic treatment is poorly understood. Prior vesicular acetylcholine transporter positron emission tomography (VAChT PET) imaging studies implicate the degeneration

BackgroundThe immune system likely plays a role in the pathogenesis of spinocerebellar ataxia type 3 (SCA3). Peripheral blood leukocytes are indicative of the immune status in neurodegenerative diseases. However, alterations in the characteristics of peripheral blood leukocytes at different stages of SCA3 and their potential roles in disease progression remain unclear.ObjectivesThe goal was to identify

BackgroundThe pathophysiology of idiopathic normal pressure hydrocephalus (iNPH) and its association with neurodegenerative disorders is poorly understood.ObjectivesThe aim was to determine the prevalence of α‐synuclein pathology in iNPH and its associations with clinical characteristics.MethodsWe used α‐synuclein seed amplification assay (synSAA) to retrospectively analyze cerebrospinal fluid (CSF)

BackgroundTemporal interference stimulation (TIS) is a novel noninvasive electrical stimulation technique to focally modulate deep brain regions; a minimum of two high‐frequency signals (f1 and f2 > 1 kHz) interfere to create an envelope‐modulated signal at a deep brain target with the frequency of modulation equal to the difference frequency: Δf = |f2 – f1|.ObjectiveThe goals of this study were to

BackgroundThe aim was to investigate if glymphatic function is impaired in patients with Huntington's disease (HD) and its clinical relevance.MethodsForty‐nine subjects carrying mutant Huntingtin (mHTT), comprising 35 manifest (mHD) and 14 pre‐manifest (PreHD), and 35 healthy controls (HC) were recruited in this study. The diffusion along perivascular spaces (ALPS) index and the percentage of perivascular

BackgroundFamilial adult myoclonus epilepsy (FAME) is a rare autosomal dominant disorder caused by the same intronic TTTTA/TTTCA repeat expansion in seven distinct genes. TTTTA‐only expansions are benign, whereas those containing TTTCA insertions are pathogenic.ObjectiveWe investigated the genetic basis of dominant cortical myoclonus without seizures in two unrelated families.MethodsRepeat‐primed polymerase

ObjectiveLow‐frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been associated with positive effects on verbal fluency (VF) in patients with Parkinson's disease. This prospective study investigates stimulation direction‐dependent and site‐specific effects of theta frequency DBS on VF.MethodsIn a double‐blind, cross‐over design (n = 20), we tested VF during left subthalamic

ObjectivesTo investigate trajectories of regional brain volume changes in multiple system atrophy (MSA) and their potential utility as surrogate markers of disease progression in the cerebellar subtype (MSA‐C).BackgroundReliable biomarkers for tracking disease progression in MSA are urgently needed. Although several studies have explored neuroimaging markers, imaging measures that are reliable and

BackgroundEpidural electrical spinal cord stimulation has been studied for more than a decade for Parkinson's disease symptoms, but compelling evidence for its effectiveness is still lacking.ObjectiveThe aim of this study was to evaluate the effectiveness of spinal cord stimulation in Parkinson's disease.MethodsParticipants had Parkinson's disease diagnosis, gait impairment and freezing of gait, and

BackgroundMotor cortex disinhibition, as measured by impaired short‐interval intracortical inhibition (SICI) using transcranial magnetic stimulation (TMS), is a well‐established feature of Parkinson's disease (PD). However, its substantial variability among patients remains unexplained, prompting questions about its origin, clinical relevance, and connection to disease heterogeneity.ObjectiveBased

BackgroundLittle is known about the prognostic value of plasma biomarkers in mild cognitive impairment with Lewy bodies (MCI‐LB).ObjectivesTo investigate the association of four plasma biomarkers with disease progression in MCI.MethodsPlasma amyloid‐beta (Aβ)42/40, glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and phosphorylated tau 181 (pTau181) were measured at baseline in a

BackgroundBridge‐like lipid transfer proteins (BLTPs) mediate bulk lipid transport at membrane contact sites. Mutations in BLTPs are linked to both early‐onset neurodevelopmental and later‐onset neurodegenerative diseases, including movement disorders. The tissue specificity and temporal requirements of BLTPs in disease pathogenesis remain poorly understood.ObjectiveThe objective of this study was

BACKGROUND Cognitive impairment in Parkinson's disease (PD) is a key non-motor complication during the disease course. OBJECTIVES A review of detailed cognitive instruments to detect mild cognitive impairment (PD-MCI) or dementia (PDD) is needed to establish optimal tests that facilitate diagnostic accuracy. METHODS We performed a systematic literature review of tests that assess memory, language including

BackgroundChronic ataxias, a complex group of over 300 diseases, pose significant diagnostic challenges because of their clinical and genetic heterogeneity. Here, we propose that artificial intelligence (AI) can aid in the identification and understanding of these disorders through the utilization of a smart virtual assistant.ObjectivesThe aim is to develop and validate an AI‐powered virtual assistant

BackgroundThe burden of non‐motor symptoms in Parkinson's disease (PD) can be measured with the Non‐Motor Symptoms Scale (NMSS) and the International Parkinson and Movement Disorder Society Non‐Motor Rating Scale (MDS‐NMS), for which scoring systems, structure and clinical coverage differ.ObjectivesThe goal was to develop conversion formulas between the NMSS and the MDS‐NMS scores.MethodsData from

BackgroundAntidopaminergic medications (ADM) are often used for symptom management of Huntington's disease (HD). Evidence from past research suggests that ADMs are associated with worse clinical outcomes in HD, but their impact on various domains remains underexplored.ObjectiveWe used causal inference analysis to understand the impact of ADM use on measures of clinical progression in HD across multiple

BackgroundDyskinesia is a motor complication of Parkinson's disease (PD) posing therapeutic challenges. The optimal therapy for dyskinesia in PD has not been identified due to the lack of comprehensive evaluation of treatments.ObjectiveThe aim was to compare the efficacy and safety of interventions for alleviating levodopa‐induced dyskinesia in PD.MethodsWe conducted a Bayesian network meta‐analysis

BackgroundSubthalamic beta oscillations are a biomarker for bradykinesia and rigidity in Parkinson's disease (PD), incorporated as a feedback signal in adaptive deep brain stimulation with potential for guiding electrode contact selection. Understanding their longitudinal stability is essential for successful clinical implementation.ObjectivesWe aimed to analyze the long‐term dynamics of beta peak

BackgroundNo objective biomarkers exist for diagnosing and classifying tremor syndromes.ObjectiveThe aim was to develop and validate a deep learning (DL) algorithm for classifying tremors from hand‐drawn pen‐on‐paper spirals.MethodsWe recruited participants with dystonic tremor (DT), essential tremor (ET), essential tremor plus (ETP), Parkinson's disease (PD), cerebellar ataxia (AT), and healthy volunteers

BackgroundLevodopa‐induced dyskinesia (LID) in Parkinson's disease (PD) is associated with ‘false neurotransmitter’ release of dopamine from serotonin (5‐HT) neurons. NLX‐112 is a first‐in‐class, highly selective 5‐HT1A receptor agonist which counteracts LIDs in experimental PD models.ObjectivesThe primary objective was to evaluate the safety and tolerability of NLX‐112 compared with placebo in people

Essential tremor (ET) is a common movement disorder with a strong genetic basis. Magnetic resonance imaging (MRI), particularly diffusion‐weighted MRI (dMRI) and T1 MRI, have been used to identify brain abnormalities of ET patients. However, the mechanisms by which genetic risk affects the brain to render individuals vulnerable to ET remain unknown. We aimed to understand how ET manifests by identifying

BackgroundPatients with mutations in the monocarboxylate transporter 8 (MCT8, SLC16A2) suffer from X‐linked recessive Allan‐Herndon‐Dudley syndrome (AHDS), which is characterized by developmental delay and a severe movement disorder. Current trials using thyroid hormone derivatives to overcome the transporter defect have failed to achieve patient‐oriented therapeutic goals.ObjectivesOur aim was to

BackgroundNovel commercial brain‐sense neurostimulators enable us to contextualize brain activity with symptom and medication states in real‐life ambulatory settings in Parkinson's disease (PD). Although various candidate biomarkers have been proposed for adaptive deep brain stimulation (DBS), a comprehensive comparison of their ambulatory profiles is lacking.ObjectivesTo systematically compare the

BackgroundADCY5‐related dyskinesia is a rare disorder caused by mutations in the ADCY5 gene resulting in abnormal involuntary movements. Currently, there are no standardized guidelines to treat this condition.ObjectiveThe aim of this study was to evaluate the efficacy of theophylline administration in improving symptoms and quality of life in patients with ADCY5‐related dyskinesia.MethodsA retrospective

ObjectiveTo update evidence‐based medicine recommendations for treating motor fluctuations of Parkinson's disease (PD).BackgroundThe International Parkinson and Movement Disorder Society (MDS) Evidence Based Medicine in Movement Disorders Committee recommendations for the treatments of PD were first published in 2002 and regularly updated. The current review uses a new methodology, including the Cochrane

Genetic factors play a central role in neurodegenerative disorders. Over the past few decades, significant progress has been made in identifying the causative genes of numerous monogenic disorders, largely due to the widespread adoption of next‐generation sequencing (NGS) technologies in both research and clinical settings. However, many likely monogenic disorders still lack an accurate molecular diagnosis

BackgroundMultiple system atrophy (MSA) shares clinical features with idiopathic Parkinson’ s disease (iPD) and progressive supranuclear palsy (PSP), yet reliable biomarkers for differential diagnosis remain elusive.ObjectivesThis study aimed to evaluate Piezo1/2 expression in urinary exfoliated cells as a potential biomarker for MSA differentiation.MethodsPiezo1/2 expression levels were quantified

BackgroundEssential tremor is hypothesized to emerge from synchronized oscillatory activity within the cerebello‐thalamo‐cortical circuit. However, this hypothesis has not yet been tested using local field potentials directly recorded from the thalamus alongside signals from both the cortex and cerebellum, leaving a gap in the understanding of essential tremor.ObjectivesTo clarify the importance of

BackgroundThe Patient‐Reported Outcome Measure of Ataxia (PROM‐Ataxia) has been validated cross‐sectionally but not longitudinally.ObjectiveWe aimed to validate PROM‐Ataxia as a measure of patient experience of disease over time, examine overall and domain‐specific progression, and test convergent validity with other clinical outcome assessments (COAs).MethodsWe derived PROM‐Ataxia data from 176 patients

BackgroundBilateral deep brain stimulation (DBS) and unilateral magnetic resonance–guided focused ultrasound (MRgFUS), with potential future second‐side treatment targeting the thalamic ventral intermediate nucleus (VIM), are currently the two best‐established interventions for pharmaco‐resistant tremors, but treatment selection is hampered by the lack of comparative evidence.ObjectiveTo provide the