Background:A growing number of identified genes increasingly reveal genetic overlaps between neurodevelopmental disorders and combined dystonia syndromes. Case report:We report a 61-year-old man with a neurodevelopmental disorder, mild ataxic signs and generalized dystonia who had been misdiagnosed with cerebral palsy for 40 years. Whole-exome sequencing identified a novel heterozygous pathogenic frameshift variant in TBL1XR1. Discussion:TBL1XR1 variants are classically associated with Pierpont syndrome and autism spectrum disorder. Although movement disorders have been reported, this case suggests generalized dystonia as a possible additional manifestation. It highlights the value of retrospective genetic phenotyping and next-generation sequencing in adults with long-standing neurodevelopmental diagnoses.
Background:Essential tremor (ET) has been increasingly recognized to involve non-motor symptoms, including sleep disturbances. Essential Tremor Plus (ET-plus), is characterized by additional neurological "soft signs" and may display greater non-motor symptom burden. Despite emerging evidence from polysomnographic studies, large-scale subjective evaluations of sleep across the ET spectrum remain limited. Objectives:To assess the prevalence and severity of sleep disturbances in ET and ET-plus using validated sleep questionnaires, and to compare with healthy controls. Methods:This study was conducted at NIMHANS, Bengaluru, and included 100 patients (60 ET and 40 ET-plus) and 100 healthy controls. Tremor severity was assessed using TETRAS and FTMRS, and sleep symptoms with ESS, PSQI, Mayo Sleep Questionnaire, RLS-Q, BQ, GAD-7 and PHQ-9. Non-parametric tests and effect size estimations were used for group comparisons. Results:ET-plus patients were older and exhibited greater tremor severity than ET. Global PSQI scores differed significantly among ET and ET Plus vs controls (p < 0.001), with ET-plus reporting the poorest sleep quality. ET and ET-plus demonstrated significantly higher ESS (p < 0.001) and greater prevalence of probable RBD, RLS, and sleep apnea risk compared with controls. Tremor disability scores correlated with PSQI scores in ET-plus, suggesting an interaction between motor and non-motor burden. Conclusions:Both ET and ET plus have significant sleep dysfunction with ET-plus patients showing markedly poorer sleep quality, higher daytime somnolence, and greater parasomnia prevalence than ET and controls. These findings highlight the clinical relevance of routine sleep assessment in ET and may impact quality of life and management.
We report a 41-year-old man of African descent from the Northern Minas Gerais/Jequitinhonha Valley region of Brazil - historically characterized by geographic isolation, predominantly Afro-Indigenous ancestry, and structural consanguinity - born to first-degree cousin parents, who presented with progressive axonal sensorimotor neuropathy, cerebellar ataxia, dysarthria, and oculomotor abnormalities. His sister had died with a similar untreated neurological syndrome. Three serial electroneuromyographic studies demonstrated stable chronic axonal polyneuropathy with complete bilateral absence of sural, fibular, and plantar sensory potentials, and active distal denervation. Brain MRI, unchanged over a two-year interval, showed T2/FLAIR hyperintense foci in both cerebellar hemispheres and the right middle cerebellar peduncle with cerebellar atrophy, without diffusion restriction or contrast enhancement. Next-generation sequencing (NGS; Mendelics®; 101-gene hereditary neuropathy panel) identified a homozygous pathogenic variant in the POLG gene (c.2243G>C; p.Trp748Ser - ClinVar ID 13507), confirming the diagnosis of mitochondrial DNA depletion syndrome type 4B (OMIM #613662). The patient's paternal great-grandfather was from the state of Ceará, a region with documented European colonization, providing a plausible route for the introduction of this classically European founder allele into his Afro-Brazilian lineage, with homozygosity emerging through consanguinity. To our knowledge, this is the first report of p.Trp748Ser in a patient of African descent, directly challenging its presumed ethnic exclusivity. Clinical and electrophysiological stability over 2.5 years is consistent with the favorable course reported in p.W748S homozygotes. This case underscores the importance of POLG-related ataxia as a diagnostic consideration in patients of non-European ancestry presenting with axonal neuropathy and cerebellar signs, and highlights the consequences of underrepresentation of populations of African descent in genetic disease research.
Background:Essential Tremor (ET) has traditionally been regarded as a pure motor disorder. However, emerging evidence suggests associations with non-motor symptoms, including cognitive impairment, psychiatric disturbances, and sleep abnormalities. REM Sleep Behavior Disorder (RBD) is a known prodromal feature of alpha-synucleinopathies such as Parkinson's disease (PD). The relationship between ET and RBD remains unclear, with previous studies reporting variable prevalence rates. Objective:This study aimed to determine the prevalence of probable RBD (pRBD) among patients with ET using the REM Sleep Behavior Disorder Single-Question Screen (RBD1Q). Methods:In this single-center, cross-sectional study, we identified ET patients from the Parkinson's Disease Center and Movement Disorders Clinic at Baylor College of Medicine. Eligible patients were contacted and screened for pRBD using the RBD1Q. A small cohort of healthy controls, including spouses, was also screened. Demographic and clinical characteristics were compared between ET patients with and without pRBD. Results:Among 245 ET patients, 21.2% screened positive for pRBD. There were no significant differences in age, age at tremor onset, or tremor duration between patients with and without pRBD. There was a significantly higher percentage of males among ET patients with pRBD (63.5% vs. 48.7%, p = 0.045). Discussion:In this study, pRBD screen positivity was relatively more common in ET patients than historical controls. These findings suggest that sleep-related symptoms may be relevant in ET and support further study with polysomnographic confirmation of RBD and longitudinal follow-up of these symptoms in ET patients.
Background:Dystonia is an under-recognized yet clinically significant feature of Progressive supranuclear palsy (PSP), contributing to disability and impaired motor function. Method:In this prospective study, we examined the clinical and neuroimaging details of eighty-eight consecutive PSP patients who visited our movement disorder clinic [2024-2025]. Patients fulfilling the 2017 Movement Disorder Society-PSP criteria for possible or probable PSP were enrolled after ethics approval and informed consent. We aimed to evaluate the prevalence, phenomenology, subtype associations, clinical and neuroimaging correlates of dystonia. Additionally, a literature search was performed and 29 articles were included for detailed review. Result:The literature review identified predominantly retrospective studies, reporting dystonia in approximately 30-60% of the patients, with variable patterns of cranio-cervical and limb involvement. In our prospective cohort, dystonia was present in 64.8% (n = 57) cases. PSP-RS was the most frequent subtype (39.8%), followed by PSP-P (26.1%) and PSP-CBS (23.8%). Dystonia was more common in PSP-RS and PSP-CBS, with predominant limb dystonia in PSP-CBS, and cranio-cervical dystonia in PSP-RS. A trend toward earlier dystonia was observed in PSP-CBS. Patients with dystonia demonstrated lower Midbrain to pons ratios and higher Magnetic resonance parkinsonism index, suggesting greater brainstem involvement. Botulinum toxin therapy resulted in clinical improvement in selected dystonia patients. Conclusion:Dystonia is a frequent and clinically meaningful feature in PSP. Our prospective study expands upon the existing literature by demonstrating distinct subtype-specific patterns and neuroimaging correlates, supporting the concept of a "dystonia spectrum" in PSP and highlighting its relevance for clinical recognition and management.
Although Lansoprazole, a proton pump inhibitor, is quite safe, there have been occasional reports of associated neurological dysfunction. We present a middle-aged man who developed bilateral asterixis within few hours of the first dose of lansoprazole. Interestingly, the jerks disappeared rapidly after discontinuation of lansoprazole.
Camptocormia is a disabling postural disorder characterized by involuntary forward flexion of the thoracolumbar spine that resolves in the supine position. It is mostly associated with Parkinson's disease and parkinsonian syndromes, but may also occur in dystonia, paraspinal myopathies, and after exposure to some drugs. Available treatments, including postural aids, medication adjustment, and deep brain stimulation, are often only partly effective and may carry risk. Because overactivity of trunk flexor muscles is thought to contribute to camptocormia, botulinum neurotoxin (BoNT) has emerged as a potential treatment. This review critically evaluates the published literature on BoNT treatment of camptocormia. We searched Medline, Google Scholar, and Scopus for English-language publications published through April 1, 2026, identifying nine reports including three case series and six single case reports. No randomized placebo-controlled trials were found. Most studies used onabotulinumtoxinA, but injection targets, dosing, and outcome measures varied. Improvement in posture, reduced pain and functional benefits were described. The most consistent benefit was with bilateral injection of the rectus abdominis and external oblique muscles, whereas isolated psoas or iliopsoas injections were less effective. Overall, BoNT appears promising for the treatment of camptocormia; however, randomized, placebo-controlled trials are needed to confirm efficacy and establish optimal treatment protocols. The studies should be conducted with caution because long-term outcome data are limited and reported efficacy has been modest.
Background:Essential tremor (ET) is one of the most common movement disorders, yet reported prevalence estimates vary widely, likely because of differences in ascertainment strategies, which can influence data validity and comparability. Electronic healthcare records (EHRs) offer an opportunity to estimate prevalence at the population level. However, the impact of these strategies remains incompletely understood, raising questions about the accuracy and generalizability of the resulting estimates. Methods:We conducted a retrospective, population-based cross-sectional study using EHR data from the Geisinger Health System (GHS) to identify cases of ET. Cases were mapped to a census-defined population of 1,081,934 individuals aged ≥10 years in Northeast-Central Pennsylvania on April 1, 2020. ET prevalence was assessed using two ascertainment strategies: (1) the neurology cohort and (2) the all-specialties cohort. Age-threshold, age-specific, and sex-stratified prevalence estimates were calculated, along with age-standardized rates based on the 2020 U.S. population. Results:Crude prevalence of ET was 0.261% (95% CI, 0.252-0.271) in the neurology cohort and 0.653% (95% CI, 0.638-0.668) in the all-specialties cohort. Age-standardized prevalence was 0.40% (95% CI, 0.39-0.41) and 1.01% (95% CI, 1.00-1.02), respectively. Prevalence increased progressively with age across both ascertainment strategies, and sex-stratified analyses demonstrated similar age-related patterns with a modest female predominance, particularly in the all-specialties cohort. Discussion:ET prevalence estimates vary substantially depending on ascertainment strategy, with broader EHR-based definitions identifying more than twice as many cases as neurologist-restricted approaches. These findings highlight the importance of standardization in improving comparability across studies.
Background:Essential Tremor (ET) is the most prevalent movement disorder in adults yet remains underrepresented in digital biomarker research. As therapies evolve, the absence of validated digital endpoints represents a growing translational gap. We introduce TRACE (Technology Readiness And Clinical Evidence), a novel five-tier validation maturity framework, and apply it in a scoping review of the ET digital biomarker literature. Methods:A PRISMA-ScR scoping review was conducted across four databases (2000-2025). Studies were eligible if they reported quantitative digital tremor measurement in ten or more ET participants. Each study was assigned to the highest satisfied TRACE tier: technical verification (T1), referenced clinical validity (T2), ambulatory and longitudinal utility (T3), clinical trial readiness (T4), or economic and implementation readiness (T5). Results:One hundred and sixty-five studies were included: wearable inertial measurement units (n = 114), digitised handwriting (n = 16), computer vision (n = 15), surface EMG (n = 10), voice (n = 6), and gait (n = 4). One hundred and fifty-four (93%) were T2; nine T3; two T4, both deploying the Cala Health TAPS wristband; none T5. Home or ambulatory deployment was present in 13 studies, minimum detectable change data in three, and patient-reported outcome correlation in 11. Discussion:Only 11 studies across two modalities were classified beyond T2, demonstrating ambulatory or longitudinal evidence beyond supervised clinical validation; the TAPS wristband is the sole platform to achieve Tier 4. Home deployment, minimum detectable change derivation anchored to patient experience, and patient-reported outcome integration remain key prerequisites before digital tremor metrics can function as trial endpoints or inform routine practice. Highlights:Despite rapid advances in digital outcome measures for Parkinson's disease, essential tremor remains largely overlooked. Reviewing 165 studies across six sensing modalities, we introduce TRACE, a five-tier validation framework, and find that while 93% of devices demonstrate basic clinical validity, only two achieve clinical trial readiness.
Background: Pisa syndrome (PS) is a reversible lateral trunk deviation that arises as a complication in a subset of patients with Parkinson's disease (PD). Effective therapeutic options remain limited, and standardized protocols are lacking. Extracorporeal shockwave therapy (ESWT), an intervention with emerging antidystonic and antispastic properties, has shown promising effects on muscle spasms and dystonia. We aimed at evaluating the feasibility, safety, and preliminary therapeutic effects of ESWT combined with botulinum toxin (BoNT) for reducing paraspinal muscle tone and pain in patients with PS. Methods: This crossover observational study analyzed data collected in routine clinical practice in patients with PS undergoing focused ESWT applied to ipsilateral paraspinal muscles immediately prior to BoNT injections. Fifteen patients were enrolled, and eleven completed the full protocol, which included ESWT+BoNT and sham ESWT+BoNT administered according to clinical scheduling, with a washout phase lasting no less than 3 months between treatment conditions. Clinical evaluations were performed at baseline, immediately post-treatment, and at 1 and 3 months post-treatment. Outcome measures included lateral trunk flexion angle, UPDRS part III scores, pain intensity ratings, quality of life assessments, and surface electromyography (sEMG) of axial muscles. Results: The primary finding was a significant immediate reduction in lateral trunk flexion following active ESWT compared with sham (p = 0.038). However, no sustained effects were observed at 1 or 3 month post-treatment for posture, motor severity, pain, or patient-reported outcomes. sEMG analysis did not demonstrate significant modifications in muscle activation patterns. ESWT was well tolerated, only mild, transient discomfort was reported, and no systemic adverse events occurred. Discussion: These findings provide evidence that focused ESWT may acutely reduce lateral trunk flexion in PS when used as an adjunct to BoNT. Larger studies are warranted to better define its therapeutic potential.
We read with interest the recent prospective study by Louis et al. examining longitudinal changes in intention tremor severity in essential tremor. The study provides valuable data addressing an important and previously understudied question regarding whether intention tremor worsens over time. While the findings demonstrate a significant group-level increase in intention tremor severity, we urge caution in extending these clinical observations to conclusions about progressive cerebellar degeneration. In the absence of direct structural, imaging, or pathological evidence, longitudinal progression of a cerebellar-related clinical sign does not necessarily confirm underlying neurodegenerative changes. Furthermore, the substantial heterogeneity observed in tremor trajectories, with a considerable proportion of patients showing stable or improved intention tremor, suggests that progression is not uniform and may reflect phenotypic variability within essential tremor rather than a universal degenerative process. Future studies incorporating direct measures of cerebellar structure and function, along with longer follow-up and phenotypic stratification, will be important to clarify the relationship between intention tremor progression and underlying cerebellar pathology.
Background: Evidence for rehabilitation after thalamotomy for writer's cramp is limited. We report immediate effects of multimodal rehabilitation. Case Report: A woman in her 20s with complex writer's cramp underwent left Vo/Vim thalamotomy. Postoperatively, she completed a 6-day program combining fine motor training, transcutaneous electrical nerve stimulation, and vibration. Thalamotomy reduced dystonia (Writer's Cramp Rating Scale [WCRS]: movement, 12 to 4; speed, 2 to 1), and rehabilitation yielded immediate writing speed gains and progressive functional recovery; although WCRS scores remained stable. Discussion: Combining bottom-up neuromodulation with task-specific training was associated with immediate gains, suggesting it may facilitate early motor relearning. Highlights A young woman with writer's cramp underwent a thalamotomy; followed by early multimodal rehabilitation that combined transcutaneous electrical nerve stimulation, vibratory stimulation, and fine motor training. Video-supported assessments and quantitative measures indicated reproducible within-session gains and short-term improvements in writing time, dexterity, and quality of life.
Clinical vignette:A 59-year-old man with essential tremor (ET) and bilateral symptoms initially underwent left thalamic MRI-guided focused ultrasound (MRgFUS) at an outside institution to address tremor in the right upper extremity. Despite an initial improvement, the benefit waned within one year, and there was significant progression of right upper extremity tremor and disabling left upper extremity tremor. Clinical dilemma:Tremor recurrence following MRgFUS highlights a common clinical challenge in the management of medication-refractory ET. When tremor re-emerges, clinicians must determine whether to pursue re-lesioning or transition to an alternative surgical strategy such as deep brain stimulation (DBS). Clinical solution:Following a multidisciplinary evaluation, staged bilateral ventral intermediate nucleus of the thalamus DBS (VIM-DBS) surgery was performed and resulted in bilateral tremor control. Gap in knowledge:There is no consensus regarding the optimal management when tremor recurs post-MRgFUS. Guiding principles for balancing re-lesioning vs. DBS remain undefined in clinical practice. Highlights:Tremor recurrence following MR-guided focused ultrasound highlights the limitations of fixed lesioning in a progressive disorder. This case illustrates that staged bilateral deep brain stimulation can provide durable, adjustable tremor control even when stimulation is delivered within a previously focused ultrasound lesioned target.
Background:Spinocerebellar ataxias (SCAs) are a diverse group of inherited disorders characterized by progressive cerebellar dysfunction. Beyond the classic ataxic features, dystonia is an important manifestation across both common and uncommon SCA subtypes. The complete clinical spectrum, pathophysiology, and treatment of dystonia in SCA remain incompletely understood. Objectives:This review aims to summarize the current literature on dystonia in SCAs, outlining its prevalence, clinical presentations, underlying mechanisms, and therapeutic strategies. Methods:The authors conducted a systematic literature review in PubMed (up to October 2025) with various search terms related to dystonia and spinocerebellar ataxia, including specific SCA types. Full text articles were included in the review based on clinical relevance. Results:Dystonia has been observed in the common SCAs such as SCA1, 2, and 3, as well as several of the rarer SCA types. While focal dystonias such as cervical dystonia and task-specific dystonia (writer's cramp) are frequent manifestations, generalized dystonias are also documented. Dystonia may follow the ataxia, or can be the presenting symptom itself. Dystonia in SCA results from dysfunction in the interconnected brain networks primarily involving the cerebellum, basal ganglia, thalamus, and sensorimotor cortex. An altered dopaminergic signalling may be present as well. Treatment responses to levodopa, anticholinergics, botulinum toxin, and deep brain stimulation vary widely, underscoring the need for individualized therapeutic approaches. Conclusions:Recognizing dystonia as a part of the SCA spectrum is important for timely diagnosis and management. Further studies are required to elucidate the mechanisms and explore the targeted interventions.
Background:Magnetic Resonance Guided Focused Ultrasound Thalamotomy (MRgFUS) is a non-surgical treatment option for medically refractory Essential Tremor (ET) or tremor dominant Parkinson's Disease. Case Report:A 75-year-old left-handed man with medically refractory essential tremor presented for MRgFUS evaluation. During workup, contrast-enhanced brain MRI revealed an incidental right frontal arteriovenous malformation. After discussion of management options, the patient elected not to pursue treatment of the newly diagnosed AVM and proceeded with tremor-focused therapy. Discussion:It is possible to effectively utilize MRgFUS for treatment of tremors in carefully selected patients with cerebral AVMs by designating the malformation as a no pass zone.
Background: Juvenile DNAJC6-associated Parkinson's disease is a rare cause of early-onset parkinsonism with limited treatment data. Case Report: We describe a 15-year-old female with a novel DNAJC6 variant presenting with progressive tremor, bradykinesia, and postural instability. Although initially responsive to levodopa, she developed severe medication-induced motor fluctuations refractory to multiple pharmacological therapies. Due to disabling tremor, bilateral globus pallidus internus deep brain stimulation (GPi-DBS) was performed, resulting in marked and sustained tremor reduction. Discussion: This case highlights the severe course of DNAJC6-associated juvenile parkinsonism and supports GPi-DBS as an effective option for refractory tremor.
Objective:To examine the risk of cervical spine complications in individuals with focal cervical dystonia (CD) treated with botulinum toxin (BoNT) injections. Background:CD is a movement disorder characterized by involuntary twisting and turning of the neck, often accompanied by a jerky tremor. Owing to the persistent abnormal forces exerted on the cervical spine, cervical spine pathology has been reported in approximately 30% of patients; however, data on this risk in the context of BoNT therapy are lacking. Design/Methods:In a retrospective analysis of CD patients receiving BoNT therapy, we determined the prevalence of cervical spine complications, including degenerative cervical spinal stenosis, myelopathy, radiculopathy, and atlantoaxial dislocation. Data on treatments including pain medications and interventions both surgical such as cervical laminectomy, discectomy, anterior cervical discectomy and fusion (ACDF), posterior cervical instrumentation and fusion (PCF), and non-surgical like radiofrequency ablation, and medial branch blocks were extracted. In addition, we conducted a literature review of cervical spine complications reported as associated with CD. Results:In a cohort of 320 patients receiving regular BoNT therapy and followed longitudinally for 5 or more years, we found 17 individuals (5.3%) with new onset cervical stenosis (n = 11), radiculopathy (n = 5) or myelopathy (n = 4), developing after the diagnosis of CD and initiation of BoNT therapy (58.8% developing in the first 5 years). The neck pain in these individuals was managed with opioid medications in addition to BoNT injections and oral muscle relaxants. While procedures such as medial branch blocks (n = 5), radiofrequency ablation (n = 2), and epidural steroid injections (n = 8) were employed for controlling pain, surgical interventions such as laminectomy (n = 3), discectomy (n = 4), PCF (n = 1), and ACDF (n = 3) were warranted in some individuals. Conclusion:Cervical spine complications following a diagnosis of CD may necessitate opioid therapy, nerve blocks, ablative procedures, and/or surgical interventions. In contrast to prior reports from the predominantly pre-BoNT era, which estimated complication rates of approximately 30%, our cohort, well managed with BoNT therapy, demonstrated a considerably lower risk of cervical spine complications (5.3%). These findings suggest that early initiation of BoNT therapy, by effectively controlling abnormal involuntary forces exerted on the cervical spine, may reduce the risk of secondary cervical spine complications.
Background: Myoclonus-dystonia (M-D) is a rare hyperkinetic movement disorder most commonly associated with SGCE mutations, while KCTD17 represents a less frequent but distinct genetic cause. Case Report: A 23-year-old man with childhood-onset Tourette-like symptoms developed progressive dystonia, upper-limb-predominant dystonia, upper-limb-predominant myoclonus, and laryngeal involvement. Genetic testing identified a pathogenic KCTD17 mutation in the patient and his affected mother. Discussion: This case illustrates that Tourette-like manifestations may occur as an early presentation of KCTD17-related myoclonus-dystonia and underscores the importance of longitudinal reassessment and genetic evaluation. Highlights This case describes a genetically confirmed KCTD17-related myoclonus-dystonia presenting with early Tourette-like features. It highlights the diagnostic complexity arising from overlapping phenomenology, the importance of longitudinal reassessment, and the role of genetic testing in atypical, progressive, or treatment-refractory tic-like presentations.
Background:The Archimedes spiral test is widely used in clinical neurology to evaluate tremor, yet its diagnostic performance for essential tremor (ET) remains unclear and methodologically inconsistent across studies. Objective:To determine the diagnostic accuracy of the Archimedes spiral test for distinguishing ET from healthy controls (HC) and to identify methodological and technological factors associated with improved performance. Methods:A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines (PROSPERO: CRD420251167793). Eight studies (1,046 participants) were included. Risk of bias was assessed with QUADAS-2. Pooled diagnostic accuracy was estimated using a random-effects model, and subgroup/meta-regression analyses examined the impact of digital acquisition, AI algorithms, EMG/accelerometry, and execution parameters. Results:The pooled diagnostic accuracy was 0.89 (95% CI: 0.77-0.95; I² = 75.4%). Technology-assisted methods (digital capture or AI-based analysis) demonstrated higher accuracy (0.91; 95% CI: 0.79-0.96) than manual approaches (0.78; 95% CI: 0.70-0.84), although differences did not reach statistical significance. Exploratory analyses suggested that medication withdrawal, absence of arm support, digital recording, and standardized execution protocols may contribute to improved diagnostic performance. Conclusions:The Archimedes spiral shows moderate-to-high diagnostic accuracy for ET, particularly when combined with digital acquisition and objective analytic methods. Given the small number of available studies and substantial methodological heterogeneity, these findings should be interpreted as exploratory. Standardized digital protocols may enhance reproducibility and support the development of scalable, clinic-ready tremor biomarkers.
