Movement Disorders Clinical Practice最新文献

Background: The globus pallidus internus (GPi) is the traditional evidence-based deep brain stimulation (DBS) target for treating dystonia. Although patients with isolated "primary" dystonia respond best to GPi-DBS, some are primary or secondary nonresponders (improvement <25%), showing variability in clinical response.

Objective: The aim was to survey current practices regarding alternative DBS targets for isolated dystonia patients with focus on nonresponders to GPi-DBS.

Methods: A 42-question survey was emailed and distributed during a DBS conference to clinicians involved in DBS for dystonia. The survey covered (1) use of alternative DBS targets as primary or rescue options, (2) target selection based on dystonia phenomenology, (3) experience with secondary nonresponders to GPi-DBS, and (4) management of patients with additional DBS leads.

Results: The response rate was 53.8%, including neurologists and neurosurgeons from 28 DBS centers in 13 countries; 89% of neurologists and 86% of neurosurgeons used alternative DBS targets to GPi, with subthalamic nucleus being the most common initial or rescue alternative to GPi. Patients with additional tremor received DBS in the ventral intermediate nucleus or caudal zona incerta. Individual experience ranged from 5 to 25 patients. Most patients were still receiving dual target stimulation at the last follow-up.

Conclusions: We show that more than 85% of surveyed clinicians use alternative DBS targets, mostly in some isolated dystonia patients not adequately responsive to GPi-DBS. More knowledge is needed to evaluate outcomes in alternative targets and establish the best strategies for managing insufficient GPi-DBS response in dystonia patients with diverse phenomenology. Our article contributes to establishing a clearer time frame and criteria for defining nonresponders in dystonia patients undergoing DBS.

Background: Stiff Person Spectrum Disorders (SPSD) are classically defined by the presence of muscle stiffness, spasms and hyperactivity of the central nervous system. There is a notable correlation between neurophysiological features and the clinical hallmark of SPSD, which has greatly encouraged the use of these techniques for diagnostic purposes. Besides, electrophysiological techniques allow for a functional evaluation of the 'hyperactivity of the CNS', thus offering the opportunity to clarify the mechanisms underlying this disorder. This review delves into the current knowledge on the electrophysiological aspects of SPSD, highlighting the pivotal role of various studies in unravelling its pathophysiology.

Methods: Literature review for studies on SPSD that included a neurophysiological evaluation.

Results: We first examined the abnormal neurophysiological findings of SPSD across the central nervous system, from the spinal circuit to the motor cortex. Subsequently, we discussed their pathological implications and explored how these findings can be interpreted within the framework of an immune-mediated disorder.

Conclusions: Two primary questions remain unanswered: the localization of the primary abnormality within the central nervous system and the connection between the autoimmune basis of SPSD and its neurophysiological aspects. Addressing these questions could provide invaluable insights into SPSD etiology and targeted therapeutic strategies.

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.