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Parkinson's disease (PD) is characterized clinically by the presence of bradykinesia, rigidity, and tremor. Although upper limb rest tremor is the most common form of tremor in PD, lip/jaw tremor is identified in a proportion of these patients. We aimed to assess the frequency, features, and correlates of lip/jaw tremor in PD. We studied 229 consecutive patients with PD. There were 39 (17%) patients with lip/jaw tremor, 22 of them (56.4%) were males. Slight lip/jaw tremor was identified in n = 10 (25.6%), mild in n = 15 (38.5%), moderate in n = 13 (33.3%) and severe in n = 1 (2.6%) case. Patients with lip/jaw tremor had a positive association with older age, greater limb rest tremor scores (P = 0.009), and higher total MDS-UPDRS-III scores (P < 0.001) in the multivariate regression analysis. There were 6 patients with isolated lip/jaw tremor (i.e. without limb rest tremor). These patients were all male (P = 0.038), tended to be older (75.7 vs. 67.7 years, P = 0.078) and had greater cognitive impairment (P = 0.034) than the rest of the cohort, but there was no association with other body tremors or total motor score. Lip/jaw tremor was identified in 17% of cases; it was associated with greater motor severity and limb rest tremor, suggesting shared pathophysiology with limb rest tremor. A subgroup with isolated lip/jaw tremor showed reduced cognitive performance, but no association with other body tremors.
Vocal tremor profoundly impacts communication, social participation, and quality of life. Although expert auditory-perceptual ratings of vocal tremor severity align with acoustic voice outcomes (e.g., extent of frequency (f o) and intensity modulation), patient perception of their voice remains unexamined despite its clinical importance. This study aimed to characterize the relationship between patient-reported vocal tremor severity and acoustic voice outcomes at baseline and after botulinum toxin injections. Patients diagnosed with vocal tremor affecting multiple structures (ETvt) or tremor only observed in the larynx (LDvt) were recruited. Participants completed the voice section of the Quality of Life in Essential Tremor questionnaire to assess patient perception and performed sustained /ɑ/ at a comfortable pitch and volume, from which acoustic voice outcomes (rate and extent of fundamental frequency [fo ] and amplitude [dB] modulation) were derived. A subset of participants received botulinum toxin injections and were reassessed within the therapeutic window (within 12 weeks). Thirty participants (29 females; mean age = 72 years, SD = 11.40) were analyzed. Participants who rated their vocal tremor as "severe" demonstrated higher rate fo (β = 1.20, 95% CI: -0.10, 2.60 Hz) and rate dB (β = 2.30, 95% CI: 0.50, 4.10 Hz) compared to participants who rated their tremor as "moderate". Participants who rated their tremor as "marked" demonstrated higher rate fo (β = 1.50, 95% CI: 0.30, 2.60 Hz) compared to "moderate" ratings. Improvements in patient perception of vocal tremor and acoustic outcomes were highly heterogenous among seven participants who received botulinum toxin. Participants reporting more severe vocal tremor demonstrated more aberrant acoustic voice outcomes. After botulinum toxin injection, substantial heterogeneity was observed in acoustic voice measures which varied based on patient perception of change. These preliminary, exploratory findings provide a foundation for future investigations to define meaningful change in this population.
Tremor is the most common movement disorder; however, the pathophysiology of tremor remains elusive. While several neuropathological alterations in tremor disorders have been observed in post-mortem studies of human brains, a full understanding of the relationship between brain circuitry alterations and tremor requires testing in animal models. Additionally, tremor animal models are critical for our understanding of tremor pathophysiology, and/or to serve as a platform for therapy development. A PubMed search was conducted in May 2018 to identify published papers for review. The methodology used in most studies on animal models of tremor lacks standardized measurement of tremor frequency and amplitude; instead, these studies are based on the visual inspection of phenotypes, which may fail to delineate tremor from other movement disorders such as ataxia. Of the animal models with extensive tremor characterization, harmaline-induced rodent tremor models provide an important framework showing that rhythmic and synchronous neuronal activities within the olivocerebellar circuit can drive action tremor. In addition, dopamine-depleted monkey and mouse models may develop rest tremor, highlighting the role of dopamine in rest tremor generation. Finally, other animal models of tremor have involvement of the cerebellar circuitry, leading to altered Purkinje cell physiology. Both the cerebellum and the basal ganglia are likely to play a role in tremor generation. While the cerebellar circuitry can generate rhythmic movements, the nigrostriatal system is likely to modulate the tremor circuit. Tremor disorders are heterogeneous in nature. Therefore, each animal model may represent a subset of tremor disorders, which collectively can advance our understanding of tremor.
Essential tremor (ET) is characterized by often disabling action tremors. No pharmacological agent has been developed specifically for symptomatic treatment. Anecdotal reports describe tremor improvement with cannabis, but no evidence exists to support these claims. We conducted a phase Ib/II double-blind, placebo-controlled, crossover pilot trial in participants with ET to investigate tolerability, safety, and efficacy of Tilray TN-CT120 LM, an oral pharmaceutical-grade formulation containing tetrahydrocannabinol (THC) 5 mg and cannabidiol (CBD) 100 mg. Our objectives were to determine if short-term THC/CBD exposure improved tremor amplitude and was tolerated. Participants with ET were randomized (1:1) to receive either TN-CT120 LM or placebo. Dose titration, driven by tolerability, was attempted every 2-3 days to three capsules daily maximum. Participants remained on the highest tolerated dose for two weeks before returning to complete assessments. After completing the first arm, participants titrated off the agent, underwent a three-week washout, and then returned for the same procedures with the alternate compound. The primary endpoint was tremor amplitude change from baseline using digital spiral assessment. Secondary endpoints explored safety and tolerability. Among thirteen participants screened, seven were eligible and enrolled. Five completed all visits; one withdrew following a serious adverse event, and another did not tolerate the lowest dose. Intent-to-treat analyses performed for six participants did not reveal significant effects on primary or secondary endpoints. This pilot trial did not detect any signals of efficacy of THC/CBD in ET. Although preliminary due to the small sample size, our data do not support anecdotal reports of cannabinoid effectiveness for ET. This double-blind, randomized, placebo-controlled efficacy and tolerability pilot trial did not detect any signals of efficacy of oral cannabidiol and tetrahydrocannabinol in reducing essential tremor amplitude using either digital outcome measures or clinical rating scales. The oral cannabinoids were well-tolerated by most (five out of seven) participants.
This prospective study is one of the largest clinical trials in essential tremor to date. Study findings suggest that individualized non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction and improves quality of life for many essential tremor patients. Two previous randomized, controlled, single-session trials demonstrated efficacy of non-invasive neuromodulation therapy targeting the median and radial nerves for reducing hand tremor. This current study evaluated efficacy and safety of the therapy over three months of repeated home use. This was a prospective, open-label, post-clearance, single-arm study with 263 patients enrolled across 26 sites. Patients were instructed to use the therapy twice daily for three months. Pre-specified co-primary endpoints were improvements on clinician-rated Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) and patient-rated Bain & Findley Activities of Daily Living (BF-ADL) dominant hand scores. Other endpoints included improvement in the tremor power detected by an accelerometer on the therapeutic device, Clinical and Patient Global Impression scores (CGI-I, PGI-I), and Quality of Life in Essential Tremor (QUEST) survey. 205 patients completed the study. The co-primary endpoints were met (p≪0.0001), with 62% (TETRAS) and 68% (BF-ADL) of 'severe' or 'moderate' patients improving to 'mild' or 'slight'. Clinicians (CGI-I) reported improvement in 68% of patients, 60% (PGI-I) of patients reported improvement, and QUEST improved (p = 0.0019). Wrist-worn accelerometer recordings before and after 21,806 therapy sessions showed that 92% of patients improved, and 54% of patients experienced ≥50% improvement in tremor power. Device-related adverse events (e.g., wrist discomfort, skin irritation, pain) occurred in 18% of patients. No device-related serious adverse events were reported. This study suggests that non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction in many essential tremor patients.
Postural tremor can sometimes occur in spinocerebellar ataxias (SCAs). However, the prevalence and clinical characteristics of postural tremor in SCAs are poorly understood, and whether SCA patients with postural tremor have different ataxia progression is not known. We studied postural tremor in 315 patients with SCA1, 2, 3, and 6 recruited from the Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA), which consists of 12 participating centers in the United States, and we evaluated ataxia progression in these patients from January 2010 to August 2012. Among 315 SCA patients, postural tremor was most common in SCA2 patients (SCA1, 5.8%; SCA2, 27.5%; SCA3, 12.4%; SCA6, 16.9%; p = 0.007). SCA3 patients with postural tremor had longer CAG repeat expansions than SCA3 patients without postural tremor (73.67 ± 3.12 vs. 70.42 ± 3.96, p = 0.003). Interestingly, SCA1 and SCA6 patients with postural tremor had a slower rate of ataxia progression (SCA1, β = -0.91, p < 0.001; SCA6, β = -1.28, p = 0.025), while SCA2 patients with postural tremor had a faster rate of ataxia progression (β = 1.54, p = 0.034). We also found that the presence of postural tremor in SCA2 patients could be influenced by repeat expansions of ATXN1 (β = -1.53, p = 0.037) and ATXN3 (β = 0.57, p = 0.018), whereas postural tremor in SCA3 was associated with repeat lengths in TBP (β = 0.63, p = 0.041) and PPP2R2B (β = -0.40, p = 0.032). Postural tremor could be a clinical feature of SCAs, and the presence of postural tremor could be associated with different rates of ataxia progression. Genetic interactions between ataxia genes might influence the brain circuitry and thus affect the clinical presentation of postural tremor.
The 12th International Meeting on Neuroacanthocytosis, Cohen Syndrome, and other VPS13-related Disorders was held on September 12th-14th, 2025, at the Jules Gonin Eye Hospital in Lausanne, Switzerland. This long-standing series of international symposia has traditionally focused on neuroacanthocytosis syndromes and associated disorders. The program further broadened its scope to include Cohen syndrome, reflecting the growing recognition of shared molecular features and common unsolved questions across VPS13-related disorders. The aim of the meeting was to present the latest updates in the field, from both clinical and basic science perspectives, and to facilitate collaboration and exchange of ideas among researchers, clinicians, and the patient community. An important aspect of these meetings is the active involvement of patients, their relatives and caregivers, who were invited to attend scientific sessions, in addition to participating in parallel patient-oriented sessions. A total of 20 oral communications were presented in eight scientific sessions accompanied by two keynote lectures, short talks by selected poster presenters, and the 2025 "Glenn Irvine Prize" award lecture.
The aim was to assess incidence, prevalence and risk factors of medication-induced tremor in African-Caribbean patients with severe mental illness (SMI). A prospective study of SMI patients receiving care from the only mental health service of the previous Dutch Antilles. Eight clinical assessments, over 18 years, focused on movement disorders, medication use, and resting tremor (RT) and (postural) action tremor (AT). Risk factors were modeled with logistic regression for both current (having) tremor and for tremor at the next time point (developing). The latter used a time-lagged design to assess medication changes prior to a change in tremor state. Yearly tremor incidence rate was 2.9% and mean tremor point prevalence was 18.4%. Over a third of patients displayed tremor during the study. Of the patients, 5.2% had AT with 25% of cases persisting to the next time point, while 17.1% of patients had RT of which 65.3% persisted. When tremor data were examined in individual patients, they often had periods of tremor interspersed with periods of no tremor. Having RT was associated with age (OR=1.07 per year; 95% confidence interval 1.03-1.11), sex (OR=0.17 for males; 0.05-0.78), cocaine use (OR=10.53; 2.22-49.94), dyskinesia (OR=0.90; 0.83-0.97), and bradykinesia (OR=1.16; 1.09-1.22). Developing RT was strongly associated with previous measurement RT (OR=9.86; 3.80-25.63), with previous RT severity (OR=1.22; 1.05-1.41), and higher anticholinergic load (OR= 1.24; 1.08-1.43). Having AT was associated with tremor-inducing medication (OR= 4.54; 1.90-10.86), cocaine use (OR=14.04; 2.38-82.96), and bradykinesia (OR=1.07; 1.01-1.15). Developing AT was associated with, previous AT severity (OR=2.62 per unit; 1.64-4.18) and tremor reducing medication (OR=0.08; 0.01-0.55). Long-stay SMI patients are prone to developing tremors, which show a relapsing-remitting course. Differentiation between RT and AT is important as risk factors differ and they require different prevention and treatment strategies.
Transcutaneous afferent patterned stimulation (TAPS) is a non-invasive, wrist-worn neurostimulation therapy that has demonstrated acute and short-term lasting tremor reduction in patients with essential tremor (ET). However, the longer-term improvement in underlying tremor severity from consistent use of TAPS has not been fully explored. We conducted a retrospective analysis of the multicenter PROSPECT trial, which evaluated twice-daily TAPS use over three months in patients with ET. Underlying tremor improvement was assessed by comparing pre-stimulation tremor severity at baseline with pre-stimulation tremor severity at 1- and 3-month follow-up visits. Tremor severity was measured using the Bain & Findley Activities of Daily Living (BF-ADL) scale and the Tremor Research Group's Essential Tremor Rating Assessment Scale (TETRAS). Responders were defined as patients demonstrating at least a 1-point improvement on any qualifying task. Among 192 patients with available data, pre-stimulation BF-ADL scores improved significantly by 2.0 points at 1 month and 2.7 points at 3 months compared with baseline (p < 0.001). Pre-stimulation TETRAS scores also showed significant improvements at both time points (p < 0.001). Measurements at 1 and 3 months were made an average of 16.2 hours after the prior stimulation session. Over 80% of patients met responder criteria for underlying tremor improvement on BF-ADL and TETRAS at both follow-up visits. Improvements were observed even among patients using TAPS approximately once daily. Consistent use of TAPS was associated with significant improvement in underlying tremor severity in patients with essential tremor. These findings suggest that regular TAPS use may confer sustained therapeutic benefit.
Although the motor and non-motor features of essential tremor (ET) have been characterized in detail, it is not known whether ET patients suffer psychologically and whether those who are close to them consider them to be suffering in this way. Fifty ET patients and 50 "close others" (COs), identified by patients "as someone who knows you well and sees you often" and who can "provide a different perspective on your well-being", reported their own depressive symptoms, daily stress, and perceptions of patient psychological suffering and patient overall suffering with validated scales. ET patients' tremor severity, duration, disability, cognition, and number of medications were also assessed. ET patients reported levels of psychological suffering within the range documented in arthritis and dementia patients from previous studies, and COs perceived significantly more psychological suffering in patients than patients reported themselves. Regression models, controlling for tremor severity, duration, and disability revealed that patients' greater psychological suffering was associated with greater patient depression. The greater perceptions of COs of patient psychological and overall suffering were associated with greater CO depression and daily stress. Sensitivity analysis showed that patients' cognitive status or number of medications did not affect the results. Multidisciplinary teams caring for ET patients should look beyond simple clinical ET indicators. They should be aware of patient experiences and perceptions of COs of psychological and overall suffering. This will help guide the development of evidence-based, supportive interventions that improve communication about the needs of ET patients and those who are close to them.
High intensity focused ultrasound (HiFU) is a relatively new incisionless intervention used for treatment of essential tremor and Parkinson's disease tremor. Understanding the indications, benefits, risks and limitations of HiFU, as well as how it compares to deep brain stimulation (DBS), is important in guiding appropriate recommendations for prospective patients. Current literature on efficacy and safety of HiFU in essential tremor and Parkinson's disease was reviewed. We additionally reviewed data on the patients who presented to our center for HiFU consultation, including outcomes of patients with low skull density ratios, and distances traveled for the procedure. HiFU is an effective and generally well-tolerated treatment for tremor. Adverse events, especially gait instability, are typically temporary but should be discussed with patients. The risk of tremor recurrence in certain patients with Parkinson's disease is also of note. Identifying appropriate candidates for either intervention remains crucial and involves considering each patient's circumstances and preferences, potential adverse effects, and practical aspects like access to follow-up and expectations. Data on bilateral HiFU lesioning, use of HiFU in patients with low skull density ratios, and emerging targets like the pallidothalamic tract are discussed as well.
Despite the significance of tremor in Parkinson's disease (PD) diagnosis, classification, and patient's quality of life, there is a relative lack of data on prevalence and relationship of different tremor types in PD. The presence of rest tremor (RT) and action tremor (AT; defined as combination of both postural and kinetic tremor) was determined and RT severity was defined using the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) at baseline in the Progression Marker Initiative (PPMI, n = 423), the Fox Investigation for New Discovery of Biomarkers (BioFIND, n = 118) and the Parkinson's Disease Biomarkers Program (PDBP, n = 873) cohorts. Across baseline data of all three cohorts, RT prevalence (58.2%) was higher than AT prevalence (39.0%). Patients with RT had significantly higher (Chi-square test, p < 0.05) prevalence of AT compared to patients without RT in the PPMI (40.0% versus 30.1%), BioFIND (48.0% versus 40.0%) and PDBP (49.9% versus 21.0%) cohorts. Furthermore, patients with AT had significantly (Student t-test, p < 0.05) higher RT severity that those without AT in PPMI (5.7 ± 5.4 versus 3.9 ± 3.3), BioFIND, 6.4 ± 6.3 versus 3.8 ± 4.4) and PDBP (6.4 ± 6.6 versus 3.7 ± 4.4) cohorts. In the BioFIND cohort, the prevalence of all types of tremor and their combinations significantly decreased from the off-state to on-state. The RT is the most frequent tremor type and present in more than half of the PD patients. However, AT is also present in nearly one-third of the PD patients. Our results also indicate that RT and AT may have cross-interactions in PD, and that dopaminergic treatment influences both RT and AT.
Myoclonus is a hyperkinetic movement disorder presenting as rapid jerky involuntary movements. The etiology of myoclonus differs between in-hospital and outpatient clinic settings. Historically, those in the hospital typically develop myoclonus from toxic-metabolic or hypoxic-ischemic etiologies, whereas those presenting to a clinic tend to have an underlying neurodegenerative etiology. We retrospectively reviewed charts of both inpatient and outpatient adult cases with myoclonus at New York Presbyterian Brooklyn Methodist Hospital over 10 years. Data were analyzed with descriptive statistical methods to elucidate demographics, etiologies, and outcomes. Overall, 279 inpatient (56.63% female aged 70.61 + 15.76 years) and 85 outpatient (52.9% female aged 64.3 + 16.3 years) individuals were included in our study. Outpatient cases were younger on average than inpatient counterparts (p < 0.05). While more Caucasian individuals were seen in the outpatient setting, more black individuals were seen in the inpatient setting; ethnic distributions did not differ significantly between the two cohorts (p > 0.05). Longer symptom duration was prevalent in outpatient cases (IQR 3-45 months) compared to inpatient (IQR < 1-4 days) ones (p < 0.05). Etiological distributions varied between the two cohorts, with toxic/drug-induced, metabolic (non-genetic), and static hypoxic/ischemic etiologies predominating our inpatient cohort, and neurodegenerative, inflammatory/autoimmune/paraneoplastic, and idiopathic etiologies more prevalent in the outpatient setting. Spinal nervous system lesion and toxic/drug-induced outpatient cases tended to present focally, but inflammatory/autoimmune/paraneoplastic etiologies were associated with axial-predominant symptoms among our outpatient cohort (p < 0.05). Responses to treatment of underlying etiology and/or anti-seizure drugs was robust in both settings overall, with over 70% of individual cases showing response. Myoclonus in the inpatient and outpatient settings have differences in etiology and symptom duration, with longer duration and more neurodegenerative and inflammatory/autoimmune/paraneoplastic etiologies predominating in the outpatient cohort compared to the inpatient one. List of causes of myoclonus do not typically differentiate between the presentation in inpatient and outpatient settings. If the causes differ by setting, listing causes by setting may aid clinicians in ranking a priori probabilities.
Classically, the onset of head tremor in essential tremor (ET) patients follows that of hand tremor, such that there is a somatotopic spread of involved areas. Here we present a series of seven self-reportedly "unaffected" relatives of ET cases. These seven were clinically asymptomatic and had normal levels of arm tremor on examination, yet each evidenced a transient head wobble on examination. We estimate the prevalence of this phenotype within the two studies from which cases were ascertained. ET cases and their self-reportedly affected and unaffected relatives, enrolled in two family studies, underwent a medical history and videotaped neurological examination. In seven self-reportedly "unaffected" relatives, a transient and subtle head wobble was seen, always during sustained phonation, speech, or reading aloud. Total tremor score (a measure of arm tremor) ranged from 5 to 12 (i.e., mild tremor within the range of normal). The prevalence of this phenotype of early head tremor was 3.7% in one study and 23.1% in the other. We present a series of seven individuals who had early head tremor in an evolving transition state from normal to ET. These cases raise a number of broad clinical, phenotypic, and pathophysiological issues about ET.
The Essential Tremor Rating Assessment Scale (TETRAS) is a popular scale for essential tremor (ET), but its activities of daily living (ADL) and performance (P) subscales are based on a structured interview and physical exam. No patient-reported outcome (PRO) scale for ET has been developed according to US regulatory guidelines. Develop and validate a TETRAS PRO subscale. Fourteen items, rated 0-4, were derived from TETRAS ADL and structured cognitive interviews of 18 ET patients. Convergent validity analyses of TETRAS PRO versus TETRAS ADL, TETRAS-P, and the Quality of Life in Essential Tremor Questionnaire (QUEST) were computed for 67 adults with ET or ET plus. Test-retest reliability was computed at intervals of 1 and 30 days. The influence of mood (Hospital Anxiety and Depression Scale, HADS) and coping behaviors (Essen Coping Questionnaire, ECQ) was examined with multiple linear regression. TETRAS PRO was strongly correlated (r > 0.7) with TETRAS ADL, TETRAS-P, and QUEST and exhibited good to excellent reliability (Cronbach alpha 95%CI = 0.853-0.926; 30-day test-retest intraclass correlation 95%CI = 0.814-0.921). The 30-day estimate of minimum detectable change (MDC) was 6.6 (95%CI 5.2-8.0). TETRAS-P (rsemipartial = 0.607), HADS depression (rsemipartial = 0.384), and the coping strategy of information seeking and exchange of experiences (rsemipartial = 0.176) contributed statistically to TETRAS PRO in a multiple linear regression (R2 = 0.67). TETRAS PRO is a valid and reliable scale that is influenced strongly by tremor severity, moderately by mood (depression), and minimally by coping skills. The MDC for TETRAS PRO is probably sufficient to detect clinically important change.
Neuropathic tremor occurs with damage to the peripheral nervous system. Guillain-Barré syndrome (GBS) causes acute paralysis following nerve inflammation sometimes resulting in long-term disability. It is unclear how frequent and severe tremor is following GBS. We aimed to assess the frequency and features of tremor following GBS. We enrolled 18 patients with GBS treated in a secondary care center within a 4-year period. Evaluations were done with the Fahn-Tolosa-Marin tremor rating scale (FTM-TRS). We compared these features with a cohort of consecutive patients with untreated essential tremor (ET). There were 13 males and 5 females with a mean age at evaluation (S.D.) of 41.5 ± 14.0 years and at GBS onset of 40.2 ± 13.7. No patient had history of tremor before GBS. Upper limb tremor was identified in 16 (89%) cases, 35.5% of patients had FTM-TRS score ≥10 points. Tremor was mostly kinetic, jerky with low amplitude with a total score of 10.94 ± 11.84 in the FTM-TRS. Compared with patients with ET, those with GBS-tremor were younger and had lower scores in all subscales of the FTM-TRS (P value < 0.05 for all comparisons). In a multivariate linear regression analysis "days of hospitalization" had a positive association with the total FTM-TRS score (P = 0.001). Tremor was common following GBS. This tremor is mild compared with patients with ET, but adds functional impact.
Focal task-specific dystonia of the musicians' arm (FTSDma) is an unusual and challenging disorder, often causing significant disability with loss of performing careers. The etiology and optimal management of this disorder remains unclear. We reviewed records and videos of 173 patients with FTSDma, 50 patients with writer's cramp (WC), and 16 with other forms of arm dystonia (OD), evaluated by a single examiner in clinical practice over a 25-year period. Detailed analysis of clinical features and videotaped examinations in slow motion (what we call "deep phenotyping") allowed separation of patients into four categories: "precision-grip" dystonia (groups I and III); "power-grip" dystonia (group II); and "proximal dystonia" (group IV). We compared these results to deep phenotyping of patients with FTSDma, WC and OD patients reported in the literature. FTSDma usually affects men, involves the right hand, and begins in the fourth decade. The precision hand of pianists and guitarists (digits 1, 2, 3) was preferentially affected in the right arm, and many of the remaining patients involved the power hand of either arm (digits 3, 4, 5). The dystonic phenotype of the bow arm of string players and drumming arm of stick drummers bore striking resemblance to WC and racquet dystonia, almost always involving the wrist, forearm or shoulder. Deep phenotyping of FTSDma reveals similarities in dystonic phenotype between instrument classes, likely related to shared technical demands, and unexpected similarities between other forms of task-specific upper extremity dystonia. A network model to explain these findings is proposed.
Essential tremor (ET) is one of the most common movement disorders. Previous estimates of ET prevalence vary due to multiple factors. This study estimated the prevalence of diagnosed ET. The prevalence of diagnosed ET was estimated among adults with continuous enrollment in 2022 and ≥1 additional year of prior baseline enrollment in the Merative™ MarketScan® Research Databases, a US administrative claims database. ET was defined as ≥2 ET claims within 12 months of one another during the 2016-2022 study period. The proportion of patients receiving treatment was defined as having a claim for possible medication for ET in 2022 among those with diagnosed ET who had an additional 6 months of follow-up following the first ET diagnosis claim. Age-standardized estimates of the number of US adults with diagnosed ET were calculated using 2024 US population census projections. The prevalence of diagnosed ET was 0.28% before age standardization, ranging from 0.06% (18-40 years) to 1.61% (≥75 years); 74% of patients overall received possible treatment. After standardization, prevalence was 0.42%; in 2024, 1.1 million US adults were estimated to have diagnosed ET. Estimates of the prevalence of diagnosed ET in the US were susceptible to the choice of case definition, nearly doubling (ie, 2.1 million US adults) with a more sensitive definition. ET affects a substantial proportion of the US adult population. Selecting appropriate case definitions and using methods such as standardization are critical for estimating valid and generalizable chronic condition prevalences with real-world data. This study found that 1.1 million US adults were estimated to have been diagnosed with essential tremor, with the sensitivity analyses yielding additional estimates. Estimating reliable and generalizable prevalences of diagnosed chronic conditions requires selection of appropriate case definitions and standardization to the general population.
In the field of translational neuroscience research, it is critical to utilize a large animal model to test the feasibility, safety, and functionality of novel therapies. Here, we describe a protocol for the development of a large animal model of tremor. In a pig model, tremor was induced with harmaline and measured with wireless accelerometers attached to the limbs. Three different doses of harmaline were tested and three repetitive injections were made at 72-hour intervals. To fully characterize the drug-induced tremor, onset time, tremor amplitude, maintained duration, and peak tremor frequency were analyzed. Harmaline-induced tremor appeared immediately following intravenous injection of harmaline. Tremor was maintained over 2 hours. Its frequency was 10-16 Hz, which was independent of doses. Dose-dependent responses were observed in tremor amplitude, triggering time, and tremor-maintained duration. Repetitive injection of harmaline desensitized the harmaline effect. We provide a detailed protocol for training, drug injection, device selection, and tremor recording optimized to create a swine model of tremor with harmaline. Our protocol provides reliable tremor in pigs and suggests pig as a valid translational large animal model of tremor.
Whether low-frequency deep brain stimulation (DBS) in the caudal zona incerta (cZi) can improve cerebellar ataxia symptoms remains unexplored. We report a 66-year-old man initially diagnosed with essential tremor and subsequently developed cerebellar ataxia after bilateral cZi DBS implantation. We tested the effects of low-frequency DBS stimulations (sham, 10 Hz, 15 Hz, 30 Hz) on ataxia severity. Low-frequency cZi DBS improves ataxic speech at 30 Hz, but not at 10 Hz or 15 Hz in this patient. Low-frequency DBS did not improve gait or stance. Therefore, low-frequency stimulation may play a role in treating ataxic speech. The finding of this case study suggests that bilateral low-frequency DBS at 30 Hz in the caudal zona incerta has the potential to improve ataxic speech but has limited impact on gait and stance. The involvement of zona incerta in speech warrants further investigation.