Movement Disorders Clinical Practice最新文献

Background: As Parkinson's disease (PD) progresses, motor fluctuations become increasingly difficult to manage with oral medications. Foslevodopa/foscarbidopa (LDp/CDp), delivered as a continuous 24-h/day subcutaneous infusion, offers continuous levodopa delivery and stable plasma levodopa levels that reduce motor fluctuations. LDp/CDp has been widely utilized since becoming commercially available.

Objectives: To provide practical guidance for clinicians on the real-world use of LDp/CDp, including information on patient selection, treatment initiation, dose adjustments, and long-term management.

Methods: This narrative review included investigator experience from studies of LDp/CDp and insights from clinicians with real-world experience with LDp/CDp, addressing many critical questions that clinicians may have when initiating and managing patients on therapy.

Results: Continuous 24-h infusion enables consistent, individualized symptom control, with improvements in motor fluctuations and quality of life. LDp/CDp therapy can be initiated, adjusted, and maintained in outpatient settings without hospitalization. While infusion site events are common, they are typically mild to moderate and manageable. Early detection and intervention are important for managing infusion site events. Systemic adverse events associated with dopaminergic therapies (eg, psychosis, hallucinations, nightmares), may require infusion rate adjustment, particularly at night. Setting clear expectations is key to successful therapy adoption and maintenance. It is essential to educate patients, care partners, and clinical teams.

Conclusions: LDp/CDp is a new treatment option for advanced PD (aPD). Treatment success depends on education, selecting appropriate patients, setting patient expectations, implementing individualized dosing strategies, and managing adverse effects.

Background: Fever and worsening rigidity in Parkinson's disease (PD) may resemble neuroleptic malignant syndrome (NMS). We examined PD patients diagnosed with NMS-regardless of whether diagnostic criteria were used-to establish the clinical characteristics and etiology.

Cases: Among 15 cases, 40% (6/15) required ICU admission, 27% (4/15) required mechanical ventilation, 80% (12/15) recovered, and 20% (3/15) died. 27% (4/15) had a reduction in carbidopa-levodopa as the primary trigger, 27% (4/15) had sepsis in addition to concurrent reductions in carbidopa-levodopa, 7% (1/15) had sepsis alone, 33% (5/15) were exposed to new or increased antidopaminergic drugs, and 7% (1/15) had deep brain stimulator (DBS) malfunction.

Literature review: Several terms to describe exacerbation of parkinsonism including NMS-like state and parkinsonism hyperpyrexia syndrome (PHS) have been proposed over the years but may be restrictive in their definitions and confounders exist.

Conclusions: Acute parkinsonism dopamine depletion syndrome (APDDS) might be a more encompassing term to describe to an acute exacerbation of preexisting parkinsonism resulting from recent reduction in dopaminergic or other Parkinson's therapy (eg, DBS failure), or exposure to antidopaminergics. Symptoms include increased rigidity, encephalopathy, hyperthermia, or autonomic instability. Sepsis is a frequent confounder and may be associated with concurrent reduction or discontinuation of carbidopa-levodopa.

Background: Impulse control disorders (ICDs) are most often associated with dopamine agonists and pulsatile dopamine replacement therapy such as oral levodopa and subcutaneous apomorphine. Intestinal levodopa-carbidopa gel may improve ICDs through rationalization of dopaminergic agents and/or a reduction of pulsatile dopaminergic stimulation, however the impact of subcutaneous foslevodopa/foscarbidopa (CSFLI) has not been reported to date.

Cases: We describe five men aged 50-68 with advanced Parkinson's disease (PD) and pre-existing ICDs who were switched to CSFLI. Four of them were transitioned directly from subcutaneous apomorphine infusions with the hope of improving ICD symptoms. All experienced worsening or persistent ICD symptoms, predominantly hypersexuality, after switching to CSFLI with a mean time to peak ICD symptoms of 4.5 weeks (range 2-6).

Conclusions: CSFLI may exacerbate ICDs in susceptible individuals. Pre-treatment screening and close monitoring are recommended.

Background: Myoclonus-dystonia (M-D) is a monogenic movement disorder, with proposed cerebellar dysfunction. Vergence eye movement deficits, characteristics of degenerative cerebellar disease, have not been studied in M-D. Cerebellar transcranial alternating current stimulation (tACS) is considered a potential therapeutic approach.

Objectives: To assess vergence and prosaccade performance as markers of cerebellar dysfunction in M-D and to evaluate the effects of cerebellar 50 Hz tACS on these eye movements.

Methods: Vergence and prosaccade performance were examined in 14 M-D patients carrying pathogenic SGCE variants and 14 healthy controls. A subgroup (n = 7) received real and sham 50 Hz cerebellar tACS in a randomized, double-blind design.

Results: M-D patients showed prolonged latency and reduced gain of convergence compared to controls. Divergence did not differ between groups. Prosaccade peak velocity was reduced in M-D patients. 50 Hz cerebellar tACS showed no effect on eye movements.

Conclusion: Impaired convergence supports cerebellar involvement in M-D. Further studies should identify affected pathways.

Background: Assessment of disease progression in Parkinson's disease (PD) usually relies on longitudinal follow-up, which is often impractical in large real-world cohorts. Cross-sectional approaches may provide pragmatic proxies to explore relative motor deterioration using routine clinical data.

Objectives: To explore clinical and non-motor correlates of estimated relative motor progression in PD using a simple ratio-based index-MDS-UPDRS Part III (OFF medication) divided by disease duration.

Methods: In this retrospective cross-sectional study, 711 patients with idiopathic PD were classified as slow or fast progressors based on the cohort median of the MDS-UPDRS III (OFF)/disease duration ratio (7.31 points/year). Motor, non-motor, demographic, and treatment-related variables were compared between groups. Multivariable logistic regression analyses were used to identify clinical features associated with higher estimated progression.

Results: Patients with higher estimated motor burden per year showed greater non-motor symptom burden, higher residual motor load (ON/OFF ratio), and a higher prevalence of the akinetic-rigid phenotype. In multivariable analyses, non-motor symptom burden, residual motor ratio, shorter disease duration, and akinetic-rigid phenotype were independently associated with higher estimated progression. Among non-motor domains, Sleep/Fatigue and Miscellaneous symptoms showed specific associations. The models demonstrated good within-cohort explanatory performance (Nagelkerke R² = 0.42-0.47) in this cross-sectional cohort.

Conclusions: This study presents a simple ratio-based proxy to explore relative motor progression in PD. While not a validated longitudinal progression measure, it may serve as a pragmatic exploratory tool for descriptive stratification of large clinical cohorts. Longitudinal validation is required.

Background: Parkinson's disease (PD) is a neurodegenerative disorder accompanied by cognitive impairment, which increases a risk of dementia as the condition progresses. Although monoamine oxidase B (MAO-B) inhibitors, such as selegiline, rasagiline and safinamide, are used to treat motor symptoms in PD, their impacts on cognitive performance remain unclear.

Objectives: This study systematically evaluated and compared the impacts of MAO-B inhibitors on global cognitive performance and performance of individual cognitive domains in patients with PD.

Methods: Databases were searched through PubMed/Medline, Embase, and Cochrane Library from the inception to May 30, 2025. Thirteen randomized controlled trials (RCTs) evaluating cognitive outcomes in patients with PD treated with selegiline, rasagiline or safinamide were included. Standardized mean differences (SMDs) for global cognition and five cognitive sub-domains were pooled, respectively, using random-effects models. Publication bias and methodological quality were also assessed.

Results: 13 RCTs met inclusion criteria. Network meta-analysis showed that only rasagiline significantly improved global cognition compared to placebo (SMD, 0.863; 95% CI, 0.064-1.663), whereas selegiline and safinamide did not show any statistical difference when compared to placebo. None of the MAO-B inhibitors demonstrated significant effects on specific cognitive sub-domains (ie, attention, executive function, memory, language, and visuospatial abilities).

Conclusions: Rasagiline may provide global cognitive benefits in PD, but MAO-B inhibitors, including rasagiline, generally did not demonstrate significant effects on individual cognitive domains. These findings suggest limited cognitive impacts of MAO-B inhibitors beyond managing the motor symptoms. Further large-scale, long-term studies using domain-specific cognitive assessments are warranted to clarify their roles in cognitive performance in patients with PD.