Journal of Movement Disorders最新文献

Objective: : Studies outlining the genetic architecture of Parkinson's disease in India are sparse, and juvenile parkinsonism is underrepresented in the literature. The objective was to study the clinical, therapeutic, and genetic profiles of patients with juvenile parkinsonism and to correlate their phenotypic-genotypic characteristics.

Methods: : This retrospective chart review was conducted in patients with suspected genetically mediated juvenile parkinsonism (onset ≤21 years) who underwent genetic testing at a tertiary care center in India from 2015-2024. The available phenotypic-genotypic characteristics were evaluated and compared between Gene (+) and Gene (-) patients.

Results: : Forty patients (22 males, 55.0%) with juvenile parkinsonism were included, with mean ages at onset and presentation of 15.85±4.96 years and 26.37±10.11 years, respectively. The mean duration of illness was 10.43±10.49 years. A positive family history was present in 40.0% of the participants, and consanguinity was present in 45%. Bradykinesia was the most common motor symptom (95.0%), and cognitive impairment was the most common nonmotor symptom (17.5%). Pathogenic/likely pathogenic variants were identified in 27 patients (67.5%), with variants in PRKN being the most common (n=8 patients), followed by those in PLA2G6 (n=7 patients). Gene (+) patients had significantly more severe disease with a better levodopa response and more frequent familial consanguinity, oculomotor abnormalities, motor fluctuations, and dyskinesia. Compared with PARK-PRKN patients, PARK-PLA2G6 patients had significantly more dystonia, gaze restriction, and pyramidal signs and more severe disease at presentation, with a lower levodopa equivalent daily dose and fewer motor fluctuations.

Conclusion: : More than two-thirds (67.5%) of the juvenile parkinsonism patients in our cohort had an underlying monogenic cause. PARK-PRKN, PARK-PLA2G6, and PARK-SYNJ1 are the common causes of genetically mediated juvenile parkinsonism in India.

Nocturnal hypokinesia (NH) is common in patients with moderate-stage Parkinson's disease (PD). This open-label, single-arm pilot study aimed to assess the effect of bedtime opicapone administration on NH and to evaluate the clinical utility of the Nocturnal Hypokinesia Questionnaire (NHQ). The primary endpoint was the change in the NHQ score from baseline to week 6. Fifteen patients were included. The mean change in the NHQ score after the 6-week treatment was -0.9 points (95% confidence interval [CI]: -2.4, 0.5; p=0.187), which was not statistically significant. However, NHQ domain 2 (getting out of bed) significantly improved, with a mean change of -0.3 points (95% CI: -0.6, -0.1; p=0.025). The administration of opicapone in patients with PD and NH did not result in a significant improvement in NH, although it was associated with an improvement in the single domain of getting out of bed. Further studies are needed to establish the efficacy of opicapone for treating NH.

Embouchure dystonia (ED) is a task-specific disorder of voluntary fine motor control that has a severe impact on musicians' ability to perform. One critical skill for professional musicians is the ability to produce sustained notes with an even loudness, however this ability in ED has not been well defined. The present study therefore examined the time-varying dynamics of loudness in ED compared to healthy musicians, as well as its relationship to F0 variability, applying sound analysis of sustained notes. The findings revealed a significantly greater varia-bility with respect to both loudness and F0 among ED patients. Furthermore, loudness and F0 variability were strongly correlated, suggesting a shared pathological basis. We conclude that F0 variability and loudness instability are reliable measures for objectively characterising ED and assisting accurate diagnosis. The incorporating of quantitative acoustic tools into future diagnostic and therapeutic frameworks has the potential to enhance the objectivity and repro-ducibility of ED assessment.

Objective: This study aims to characterize the phenotypic spectrum and therapeutic outcome of patients with DYT-TOR1A of Indian and Asian origin.

Methods: A retrospective chart review of patients with genetically confirmed DYT-TOR1A (c.907_909delGAG;p.Glu303del variant) from a tertiary care centre in India.

Results: 12 patients (11 males, 91.7%) were recruited with a median age at onset of 10.5 years (8-17years) and duration of five years (2months - 31years). All had an isolated and progressive dystonia phenotype. Eight patients (66.7%) had onset in childhood, and limb-onset was noted in 10 (83.3%) patients. Five patients (41.7%) underwent bilateral GPi-DBS within a median duration of 4 years (2.5-6.5 years) from the onset with significant improvement.

Conclusion: This Indian patient cohort shows a strong male predominance and a consistent early involvement of the upper limbs. A shorter duration of illness with greater severity highlights the need for early recognition and potential surgical intervention.

Beta-propeller protein-associated neurodegeneration (BPAN) is a rare X-linked disorder caused by pathogenic variants in WDR45 gene. Early diagnosis remains challenging due to nonspecific presentations in childhood. We report six pediatric patients with BPAN, identified through genetic testing performed during the evaluation of neurodevelopmental disorders. All were female and exhibited early developmental delay, severe language impairment, and varying degrees of motor dysfunction. Seizures occurred in four patients with varying severity. Two patients showed signs of central precocious puberty. Serum neuron-specific enolase was elevated in all tested patients. Brain MRI revealed corpus callosum thinning in all cases. Iron accumulation in the substantia nigra and globus pallidus was observed in only two older patients. WDR45 variants included two nonsense, two splice-site, one in-frame deletion, and one novel frameshift deletion. Our findings highlight early clinical features that may aid in recognizing BPAN prior to the emergence of distinctive MRI abnormalities or degenerative-phase manifestations.