Movement Disorders最新文献

Background: Spinocerebellar ataxia type 2 (SCA2) is a rare, inherited neurodegenerative disease characterized by progressive deterioration in both motor coordination and cognitive function. Atrophy of the cerebellum, brainstem, and spinal cord are core features of SCA2; however, the evolution and pattern of whole-brain atrophy in SCA2 remain unclear.

Objective: We undertook a multisite, structural magnetic resonance imaging (MRI) study to comprehensively characterize the neurodegeneration profile of SCA2.

Methods: Voxel-based morphometry analyses of 110 participants with SCA2 and 128 controls were undertaken to assess groupwise differences in whole-brain volume. Correlations with clinical severity and genotype, and cross-sectional profiling of atrophy patterns at different disease stages, were also performed.

Results: Atrophy in SCA2 versus controls was greatest (Cohen's d >2.5) in the cerebellar white matter (WM), middle cerebellar peduncle, pons, and corticospinal tract. Very large effects (d >1.5) were also evident in the superior cerebellar, inferior cerebellar, and cerebral peduncles. In the cerebellar gray matter (GM), large effects (d >0.8) were observed in areas related to both motor coordination and cognitive tasks. Strong correlations (|r| > 0.4) between volume and disease severity largely mirrored these groupwise outcomes. Stratification by disease severity exhibited a degeneration pattern beginning in the cerebellar and pontine WM in preclinical subjects; spreading to the cerebellar GM and cerebro-cerebellar/corticospinal WM tracts; and then finally involving the thalamus, striatum, and cortex in severe stages.

Conclusion: The magnitude and pattern of brain atrophy evolve over the course of SCA2, with widespread, nonuniform involvement across the brainstem, cerebellar tracts, and cerebellar cortex; and late involvement of the cerebral cortex and striatum. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: Dysregulated leukotriene signaling is proposed to be involved in pathogenesis of Parkinson's disease (PD).

Objective: The objective was to examine the safety and tolerability of montelukast, a cysteinyl-leukotriene receptor1 and GPR17 antagonist, in patients with PD. Secondary outcomes were target engagement, effects on PD signs/symptoms, and central neuroinflammation.

Methods: Fifteen PD patients were recruited to a 12-week open-label trial of 20 mg bi-daily montelukast treatment. Patients underwent ratings with the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS), the Montreal Cognitive Assessment (MoCA), Beck's Depression Inventory (BDI), Parkinson's Disease Questionnaire-39 (PDQ-39), [¹¹C]PBR28-PET, and lumbar punctures before and during montelukast treatment.

Results: All patients completed the study. Three patients reported loose stool. No serious adverse events related to treatment were reported. MDS-UPDRS-Total scores improved by 6.9 points. Very low levels of montelukast were detected in all cerebrospinal fluid (CSF) samples and resulted in a reduction in inflammation/metabolism markers. [¹¹C]PBR28 binding was lowered in high, but not mixed, affinity binders after montelukast.

Conclusions: Montelukast crosses the blood-brain barrier at very low levels and is well tolerated and safe in PD patients. Preliminary effects on neuroinflammation and clinical scores motivate a future randomized controlled trial (RCT) in PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: The Movement Disorders Society Unified Parkinson Disease Rating Scale (MDS-UPDRS), Part III, is the gold standard for assessing motor symptoms in Parkinson's disease (PD). However, motor symptoms fluctuate significantly from day to day, potentially limiting the sensitivity of this scale for trials with short duration and crossover designs. This study investigated whether day-to-day variability in motor symptoms exceeds the minimal clinically important difference (MCID) in the MDS-UPDRS, Part III.

Methods: Twenty PD participants (Hoehn & Yahr stages 1.5-3) underwent 10 weekly off-medication assessments by one assessor on the same morning. Several determinants of day-to-day variability were explored.

Results: Symptom variability often exceeded the MCID for worsening and improvement. Current mental stress and fatigue did not correlate with worse scores, nor did physical activity and sleep quality in the previous week.

Conclusions: These findings suggest that day-to-day symptom variability impacts MDS-UPDRS scores in smaller and shorter-duration trials of symptomatic interventions. Continuous monitoring using wearable sensors may offer more accurate and reliable measures for evaluating PD motor symptoms in clinical studies. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: Pallidal neurostimulation is an effective treatment for severe isolated dystonia, but long-term data from clinical trials are lacking.

Objectives: To evaluate long-term efficacy and safety of pallidal neurostimulation in patients with isolated generalized or segmental dystonia.

Methods: Extension study of the prospective multicenter trial (n = 40; July 2002 to May 2004), all patients received effective stimulation and underwent regular follow-up. The 10-year follow-up (n = 31) included Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor and disability score, Beck Depression Inventory, Beck Anxiety Inventory, and Mattis Dementia Rating Scale. Primary and secondary endpoints compared motor symptoms, disability scores, mood, and cognition changes.

Results: Thirty-one patients (12 female), aged 23-72 years, completed the 10-year study extension. Per protocol analysis showed sustained significant improvement in BFMDRS motor scores at 10 years compared with baseline, without significant change from the 6-month or 5-year follow-up. On average, motor scores decreased by 25.3 ± 5.2 points at 10 years (P < 0.0001; 56% improvement). Individual outcomes varied, with 27 responders (≥25% improvement; mean improvement 65.2 ± 21.4%) and 13 non-responders compared with baseline. Sustained improvements were seen in disability, mood, and anxiety scores. Cognition remained stable.

Conclusions: This study presents the longest prospective, multicenter follow-up of pallidal neurostimulation in generalized and segmental dystonia. Two-thirds of patients showed strong and stable long-term improvements of dystonia, confirming sustained efficacy and safety over 10 years in treatment-refractory dystonic patients. However, one-third experienced primary (3/40) or secondary (10/40) treatment failure. Diagnostic advances, including genetic testing, and technological progress in pallidal neurostimulation may help to reduce the non-responder rates in the future. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: Recent studies have suggested that retinal changes measured with optical coherence tomography are detectable in early Parkinson's disease (PD), highlighting the potential of ophthalmic biomarkers for diagnosis and monitoring.

Objective: We set out to investigate the relationship between optic disc pallor measured in fundoscopy images and both prevalent and incident PD.

Methods: We analyzed color fundus photographs from 787 UK Biobank participants: 89 with prevalent PD, 317 with incident PD, and 381 age- and sex-matched controls. Optic disc pallor in several zones was quantified using semi-automated software. We used logistic and linear regression, adjusted for relevant covariates, to test for associations between disc pallor and PD status and duration.

Results: Participants with prevalent PD had significantly paler optic discs globally (OR per standard deviation [SD] increase = 1.39 [CI: 1.08-1.81], P = 0.012) and across several zones compared to controls. Each year since PD diagnosis was associated with a 1.37 SD increase in global pallor (standardized β = 1.37 [SE = 0.61], P = 0.029), and a similar increase across several zones, however, this finding was sensitive to outliers with long disease duration. No significant associations were observed for the incident PD group.

Conclusions: Optic disc pallor is significantly associated with PD and may become more pronounced with disease duration. This suggests that optic disc pallor, measured in routinely taken color fundus photographs, may serve as a biomarker for PD-related neurodegeneration. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.