Movement Disorders Clinical Practice最新文献

Background: Dystonia may respond to VMAT2 inhibition.

Objectives: Providing pilot data on the safety, tolerability, and efficacy of deutetrabenazine in non dopa-responsive dystonia.

Methods: Deutetrabenazine was titrated by adults with isolated dystonia. Primary study endpoints included the proportion who maintained the individual, maximum tolerated dose for 6 weeks, and how many titrated to 48 mg/day. Secondary endpoints included rates of QTc prolongation/arrhythmias, suicidality, excessive daytime sleepiness, cognitive decline, and drug-induced parkinsonism. Exploratory endpoints for clinical efficacy were assessed.

Results: Among 15 participants, four (26.7%) withdrew early and six (40%) titrated to 48 mg/day. Common adverse events included fatigue and diarrhea. Secondary safety endpoints did not change significantly, but MDS-UPDRS III scores worsened by ≥3 points in seven participants (46.7%). PGI-C and the blinded CGI-C and GDS improved in three women with blepharospasm.

Conclusions: Most participants tolerated deutetrabenazine for 6 weeks, and those with blepharospasm may have benefitted from its use.

Background: Genomic variations associated with dystonia in Asian Indians remain largely unknown.

Objectives: To identify genomic alterations associated with dystonia in the Asian Indian population using next generation sequencing approaches.

Methods: From September 2018 to December 2023, we enrolled 745 individuals including probands with dystonia and family members, in the Indian Movement Disorder Registry and Biobank. Clinical and demographic data were captured on a REDCap platform. We performed whole exome sequencing (WES) on DNA specimens obtained from 267 individuals with isolated, combined or complex dystonia. Variants were classified according to joint guidelines of American College of Medical Genetics and Genomics (ACMG) and Association of Molecular Pathology (AMP).

Results: The mean age of the WES cohort was 33.8 ± 16.2 years, and mean age at onset (AAO) of dystonia was 25.6 ± 17.7 years. 62.2% had isolated dystonia, 7.9% combined and 29.2% had complex phenotypes. WES identified pathogenic/ likely pathogenic variants in 54 patients (20.2%) including 14 novel variants in known dystonia genes. Variants in THAP1 were most common followed by PANK2, GLB1, PLA2G6, TOR1A, ANO3, VPS16, SGCE, SPG7, FTL and other genes. Multifocal/generalized distribution of dystonia [OR: 4.1; 95% CI 1.4-12.2, P = 0.011] and family history [OR: 4.3; 95% CI 2.1-8.9, P < 0.001] were associated with positive yield on WES.

Conclusion: THAP1 was the most frequent dystonia associated gene in this cohort. Singleton WES identifiedpotentially pathogenic variants in approximately one out of five patients tested, and contributed to management decisions in 4%.

Background: Impulse control disorders (ICD) are common side effects of dopaminergic treatment in Parkinson's disease (PD). Whereas some studies show a reduction in ICD after subthalamic nucleus deep brain stimulation (STN-DBS), others report worsening of ICD or impulsivity.

Objective: The aim was to study ICD in the context of STN-DBS using an objective measure of decision-making.

Methods: Ten PD patients performed an effort-based decision-making task alongside neuropsychiatric and cognitive evaluation before and 4 months after STN-DBS. Further, 33 PD patients underwent the same experimental procedures just once after an average 40 months of chronic STN-DBS. Participants were examined preoperatively in the medication on state and postoperatively in the medication on/stimulation ON state. Mixed linear models were used to assess the impact of ICD and STN-DBS on acceptance rate and decision time in the task while controlling for motor symptom burden, cognitive measures, and dopaminergic medication.

Results: Results revealed an increased willingness to exert high levels of effort in return for reward in patients with ICD, but acceptance rate was not modulated by chronic STN-DBS. Further, ICD, cognitive processing speed, and STN-DBS were all identified as positive predictors for faster decision speed. ICD scores showed a tendency to improve 4 months after STN-DBS, without an increase in apathy scores.

Conclusions: Chronic STN-DBS and ICD facilitate effort-based decision-making by speeding up judgment. Furthermore, ICD enhances the willingness to exert high levels of effort for reward. Both STN-DBS and dopaminergic medication impact motivated behavior and should be titrated carefully to balance neuropsychiatric symptoms.

Background: Limited evidence exists regarding the meaningfulness of symptoms experienced in early Parkinson's disease (PD).

Objectives: To identify the most bothersome symptoms experienced by people with early PD, leveraging data from the Parkinson's Disease Patient Report of Problems (PD-PROP) questionnaire within the Fox Insight Study.

Methods: Individuals with a self-reported diagnosis of PD completed the PD-PROP questionnaire, reporting up to five most bothersome symptoms. Symptom types and frequencies were derived through a combination of human expertise and machine learning.

Results: Participants (N = 8536) were 0.9 years since diagnosis, predominantly white (96%), male (53.3%), and with an average age of 64.6 years. Top most bothersome motor symptoms were tremor (55.9%) and gait issues (36.7%). Top most bothersome non-motor symptoms were pain/discomfort (33.1%) and physical fatigue (27.5%).

Conclusions: This study underscores the complexity of early PD symptomatology. Future consideration of diverse patient experiences is needed to improve therapeutic and outcome measurement strategies.

Background: Patients with parkinsonism are more likely than age-matched controls to be admitted to hospital. It may be possible to reduce the cost and negative impact by identifying patients at highest risk and intervening to reduce hospital-related costs. Predictive models have been developed in nonparkinsonism populations.

Objectives: The aims were to (1) describe the reasons for admission, (2) describe the rates of hospital admission/emergency department attendance over time, and (3) use routine data to risk stratify unplanned hospital attendance in people with parkinsonism.

Methods: This retrospective cohort study used Clinical Practice Research Datalink GOLD, a large UK primary care database, linked to hospital admission and emergency department attendance data. The primary diagnoses for nonelective admissions were categorized, and the frequencies were compared between parkinsonism cases and matched controls. Multilevel logistic and negative binomial regression models were used to estimate the risk of any and multiple admissions, respectively, for patients with parkinsonism.

Results: There were 9189 patients with parkinsonism and 45,390 controls. The odds of emergency admission more than doubled from 2010 to 2019 (odds ratio [OR] 2.33; 95% confidence interval [CI] 1.96, 2.76; P-value for trend <0.001). Pneumonia was the most common reason for admission among cases, followed by urinary tract infection. Increasing age, multimorbidity, parkinsonism duration, deprivation, and care home residence increased the odds of admission. Rural location was associated with reduced OR for admission (OR 0.79; 95% CI 0.70, 0.89).

Conclusions: Our risk stratification tool may enable empirical targeting of interventions to reduce admission risk for parkinsonism patients.

Background: Reduced cerebrospinal fluid (CSF) clearance may play a vital role in the pathogenesis of normal pressure hydrocephalus (NPH), but the radiologic marker is yet to be elucidated.

Objectives: This open-label study presents two novel neuroimaging biomarkers based on enlarged perivascular spaces (ePVS) of the sub-insular territory: the Hedgehog and Hedgehog-Halo (H-H) sign, designed to predict gait symptom severity and tap response in NPH.

Methods: We retrospectively reviewed 203 patients with possible NPH with baseline magnetic resonance imaging and gait analyses before and after lumbar puncture (LP). The Hedgehog/H-H sign was scored using T2-weighted images. The clinical severity at baseline and post-tap gait improvement was compared in patients with and without Hedgehog/H-H sign. The association between Hedgehog/H-H sign and post-tap gait outcomes was assessed using multivariate regression. The diagnostic performance of Hedgehog/H-H sign was compared with conventional radiological markers.

Results: Patients with H-H showed higher global disability and more severe gait impairment than those without any signs. Following LP, patients with Hedgehog/H-H sign significantly improved in various gait parameters, unlike those with neither sign. Additionally, sub-insular ePVS was significantly associated with post-tap gait improvement after adjusting covariates. Finally, the Hedgehog/H-H sign showed a higher performance than conventional markers in predicting post-tap gait response.

Conclusions: The Hedgehog/H-H sign is a useful neuroimaging biomarker related to the severity and tap response in NPH. This biomarker can be readily applied in clinical practice before undergoing LP, independent of conventional radiological signs. Further research is warranted to determine applicability in predicting post-shunt gait response.

Background: Few studies have examined the effectiveness and duration of mindfulness-based therapies for tics in Tourette's syndrome. This study combined habit reversal therapy (HRT) with acceptance and commitment therapy (ACT).

Objectives: To evaluate the efficacy and response duration of HRT + ACT in reducing tic severity in adults with Tourette's Syndrome.

Methods: Tic severity was assessed at baseline, post-intervention, and at 6- and 12-month follow-ups using the Yale Global Tic Severity Scale (YGTSS) and video assessments. The intervention included eight weekly 1-h sessions.

Results: Mixed-effects regression showed significant reductions in tic severity post-treatment (b = -10.36, P = 0.002), maintained at 6 months (b = -8.19, P = 0.012) and 12 months (b = -8.82, P = 0.009). Video assessments confirmed these findings.

Conclusion: The HRT + ACT protocol effectively reduced tic severity, with benefits lasting 12 months. These results support further trials to compare HRT + ACT with HRT alone.