Journal of Movement Disorders最新文献

Objective: Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive neuroendocrine disorder characterized by a variety of endocrine and neurological manifestations, including extrapyramidal symptoms and intellectual disability.

Methods: This report presents the genetic characterization of five Iranian patients with WSS, including the first Iranian patient to undergo deep brain stimulation (DBS).

Results: We highlight five Iranian patients with mutations in the DCAF17 gene presenting with variable features of WSS, with symptom onset in early adolescence. Whole exome sequencing identified four homozygous variants (c.436delC, c.982-2A>G, c.580C>T, and c.838+1G>A) within the DCAF17 gene in the probands. Patients had variable responses to common therapies, and one patient achieved significant improvement following DBS.

Conclusion: We expand the clinical and genetic heterogeneity among Iranian patients and suggest the c.436delC variant as a founder mutation in the region. We highlight the importance of considering WSS in patients with both neurological and endocrine symptoms and suggest DBS as a potential treatment option.

Objective: People with Parkinson's disease (PwPD) experience a gradual decline in bed mobility independence as the disease progresses. Identifying factors associated with nonindependence in daytime bed mobility is crucial for developing effective interventions to increase independence. We investigated factors associated with nonindependence in daytime bed mobility in PwPD.

Methods: This cross-sectional study included 109 PwPD (Hoehn and Yahr [HY] stage 2-4). Patients' bed mobility ability (turning in bed, supine-to-sitting, and sitting-to-supine) was assessed during the daytime, and they were categorized into independent and nonindependent groups. Potential factors associated with bed mobility independence, including components of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (rigidity, bradykinesia, tremor, axial symptoms), neck/trunk/hip strength, the Mini-Mental State Examination, and the Trail Making Test-A and B, were evaluated.

Results: The nonindependent group presented significantly increased axial symptoms, increased rigidity in the upper and lower limbs and neck, increased upper limb bradykinesia, and decreased trunk flexion/extension strength in all bed mobility tasks (p<0.05). Multivariate regression analyses revealed that axial symptoms, upper limb rigidity, and trunk extension strength were highly discriminative for nonindependence in turning in bed (the area under the curve [AUC]=0.84). Similarly, upper limb rigidity and axial symptoms were predictive of nonindependence in supine-to-sitting and sitting-to-supine movements (AUC=0.78, 0.92). A significant difference in axial symptoms between the HY stage 4 subgroups was observed only in the sitting-to-supine movement.

Conclusion: Our findings indicate that axial symptoms and upper limb rigidity are key factors contributing to nonindependence in daytime bed mobility tasks among PwPD. Targeting these factors in rehabilitation may help mitigate the decline in bed mobility independence in PwPD.

Objective: To evaluate the efficacy of istradefylline in Parkinson's disease patients experiencing motor fluctuations with and without dyskinesia and characterize potential predictors for treatment-emergent dyskinesia with istradefylline.

Methods: Pooled analysis of 8 phase 2b/3 trials of istradefylline (20 or 40 mg/day) versus placebo.

Results: Data from 2,719 patients, 56% of whom presented with baseline dyskinesia, were analyzed post hoc. The presence of baseline dyskinesia did not affect the mean decrease in "OFF" time with dyskinesia, increase in "ON" time without troublesome dyskinesia, or improvement in the Unified Parkinson's Disease Rating Scale motor score associated with istradefylline treatment. Dyskinesia was reported in 17% of patients receiving istradefylline, with higher rates for women (21%), patients with a BMI <18.5 kg/m2 (22%), and patients receiving catechol-o-methyltransferase inhibitors plus dopamine agonists (22%) and monoamine oxidase B inhibitors (25%).

Conclusion: Istradefylline treatment resulted in greater reductions in total "OFF" hours/day and increases in "ON" time without troublesome dyskinesia than did placebo, regardless of the presence or absence of preexisting dyskinesia.

Objective: Delayed ON is a condition in which Parkinson's disease (PD) patients do not experience the effect of levodopa in time after taking the dosage. The ability of various oral levodopa regimens to overcome this problem has been poorly investigated. To evaluate the efficacy of levodopa/benserazide dispersible tablets in PD patients with delayed ON to the first morning dose.

Methods: This multicenter, randomized, crossover trial involved 40 eligible PD patients with delayed ON. The participants were randomized to receive either levodopa/benserazide 100 mg dispersible or regular tablets for 4 weeks, followed by a one-week wash-out interval and an alternate drug for another 4 weeks. Participants took the investigational drug with the first morning dose of their antiparkinsonian medications. Other medications were not changed during the trial. The primary outcome was changes in time-to-ON after the first-morning dose recorded in a special diary before and after each therapy. We also evaluated changes in parkinsonism, motor fluctuations, and dyskinesia using the Unified PD Rating Scale and the Unified Dyskinesia Rating Scale. Finally, we investigated whether efficacy was affected by Helicobacter pylori status via baseline serum samples from every participant.

Results: Nine patients dropped out during the trial. The time-to-ON was significantly reduced by the dispersible tablet compared with the regular tablet (-34.72 vs. -23.81 minutes, p=0.014). There were no significant changes in parkinsonian severity or dyskinesia with either drug. The dispersible formulation was beneficial for both Helicobacter pylori-positive and -negative groups.

Conclusion: Levodopa/benserazide dispersible formulations can improve time-to-ON without exacerbating dyskinesia in PD patients suffering from delayed ON.

Research on the pathophysiology of Parkinson's disease (PD) has traditionally been performed with functional magnetic resonance imaging (fMRI); however, only a few studies have been conducted in longitudinal cohorts. In the present literature review, we aim to summarize the most recent progress in functional fMRI studies in prospective cohorts and, more specifically, in combination with other biomarkers to track the disease progression of PD. This review focuses on the potential application of multimodal longitudinal functional approaches based on the current evidence for the purpose of understanding disease progression and monitoring future therapeutic interventions.