Movement Disorders Clinical Practice最新文献

Background: Gait and mobility impairments are early markers of disease-related decline in individuals with Friedreich's ataxia (FRDA).

Objectives: This study aimed to identify the digital gait measures most discriminative of individuals with FRDA from healthy controls (HC) during an instrumented walking assessment. We also investigated if top discriminative gait measures correlated with disease severity.

Methods: We recruited 24 participants with FRDA and 24 HCs to complete a 2-min walk at a natural pace while wearing six wearable sensors on the hands, feet, sternum, and lower lumbar area. AUCs between FRDA and HC compared 51 gait measures, including standard deviations as estimates of variability, to discriminate between ataxic and normal gait. Spearman's correlation coefficients assessed the relationships between the most discriminative measures and ataxia severity from clinical outcome measures.

Results: We identified 10 measures with strong discriminative ability for gait characteristics of FRDA. The most discriminative measure was double-support time SD (AUC = 0.98, ICC = 0.95); a measure of variability. Eight out of the 10 most discriminate measures involved excessive gait variability in the FRDA group. The top five discriminative gait measures significantly correlated with the mFARS USS (r = 0.45-0.63) and two discriminative gait measures significantly correlated with the FARS ADL (r = 0.62 and 0.5). Test-retest reliability of the top measures were high (ICC = 0.85-0.98).

Conclusions: Digital gait measures from wearable sensors were discriminative, reliable, and showed concurrent validity for evaluating ataxia severity during an instrumented walk test. These results suggest promising utility of digital gait outcomes for use in FRDA clinical trials.

Background: Equitable representation in clinical trials is essential to informing evidence-based treatment and reducing health disparities. No evidence is available about racial, ethnic and sex representation in Tourette's Syndrome (TS) treatment trials.

Objectives: To evaluate racial, ethnic and sex representation in randomized controlled trials (RCTs) of TS medications.

Methods: We searched CENTRAL, Embase, PsycINFO, PubMed, Web of Science Core Collection and ClinicalTrials.gov for TS RCTs conducted in the US. The primary outcome was participation-to-prevalence ratio (PPR), the proportion of trial participants in racial, ethnic and sex subgroups divided by the proportion of individuals in the corresponding subgroup in the US population. Data were pooled through random-effects meta-analysis. Temporal trends were explored using meta-regression.

Results: Overall, 40 RCTs involving 1717 participants were included. All trials reported sex, but only 22 (55%) and 12 (30%) provided race and ethnicity data, respectively. Reporting of race and ethnicity improved over time (meta-regression coefficient (b) 1.80, 95% confidence interval [CI] 0.62-2.98 per decade, P = 0.002). Asian (PPR 0.46, 95% CI 0.29-0.75, P = 0.002), Black (PPR 0.44, 95% CI 0.34-0.57, P < 0.001), Hispanic (PPR 0.41, 95% CI 0.27-0.64, P < 0.001) and female (PPR 0.75, 95% CI 0.65-0.85, P < 0.001) individuals were underrepresented. Only Hispanic enrollment improved over time (b 0.78, 95% CI 0.35-1.20 per decade, P < 0.001).

Conclusions: There are disparities in racial, ethnic and sex representation in RCTs of TS medications. Under-enrollment of minority participants may reflect disparities in terms of actual diagnosis of the condition, recruitment of minority individuals for participation in research studies or both.

Background: There is a need to better evaluate Parkinson's disease (PD) impact on daily lives of People with Parkinson's (PwP).

Objectives: To conceptualize a novel digital tool, the MDS PD e-Diary that has been commissioned by the International Parkinson's disease and Movement Disorders Society.

Methods: Using a modified Delphi methodology, we sought consensus among key stakeholders (PwP, care partners, PD specialists, industry, regulatory representatives) through online questionnaires, focus groups, and a broad community survey.

Results: The consensus resulted in a multiplatform patient-reported outcome tool to track PD progression. It includes an Item Bank of symptoms and activities featuring two interconnected user modes. The personal mode is a customizable self-tracking tool that allows data sharing with professionals to improve standard care. The research mode employs a predefined responsive item to enhance research and clinical trials.

Conclusion: The MDS PD e-Diary was designed to capture PD progression and its impact on PwP lives, potentially transforming research and clinical practice. Its further development and validation processes are underway.

Background: Effective drug treatment of motor and non-motor symptoms in Parkinson's disease (PD) often requires the administration of several anti-Parkinson drugs in complex treatment regimens. The successful autonomous application of drugs places high demands on therapy adherence, which in turn relies on sufficient medication knowledge. However, limited information exists regarding the medication knowledge among PD patients.

Objectives: The aim of this study was to determine the knowledge of PD patients regarding drug treatment, device-aided therapies and to explore potential factors influencing this knowledge.

Methods: The study was conducted as a prospective, cross-sectional, interview-based investigation, enrolling 70 patients. Knowledge on medication was standardized according to the number of drugs taken and expressed as a medication knowledge quotient (MKQ).

Results: The median MKQ was reasonably high at 4.9 (IQR 3.5-5.9), without influence of sex and disease duration. Increasing age (p = 0.003), decreasing cognitive function (p < 0.001), low educational attainment (p < 0.001) and dispensing responsibility for drug provision (p < 0.001) negatively influenced MKQ. Knowledge regarding anti-Parkinson's drugs (ATC N04) was significantly higher than knowledge of other drug classes (p < 0.001). In contrast, knowledge of device-aided treatment options was poor.

Conclusion: PD patients displayed a high level of medication knowledge, particularly regarding anti-Parkinson's drugs. Age and the accompanying cognitive impairment had a negative impact on medication knowledge. By contrast, knowledge of the key features of device-aided treatment options requires considerable improvement.

Background: Parkinson's Disease (PD) is a progressive neurodegenerative disorder primarily characterized by motor symptoms such as tremors, rigidity, and bradykinesia. Structural brain changes, including atrophy in the midbrain, basal ganglia, and cortical regions such as the frontal and temporal lobes, are observed in advanced stages. Deep brain stimulation (DBS) is an established treatment for motor symptoms in advanced PD, significantly improving motor function and quality of life. However, its effects on brain structure and function remain poorly understood, with conflicting cognitive outcomes and growing interest in potential disease-modifying effects.

Objectives: This review aims to summarize published neuroimaging studies investigating structural and functional brain changes following DBS treatment in PD patients.

Methods: A literature search was conducted to identify neuroimaging studies that examined post-DBS brain changes in PD patients. Studies reporting findings on metabolism, blood flow, functional connectivity, and structural atrophy were reviewed.

Results: Published findings indicate increased metabolism, blood flow, and connectivity in multiple motor-related regions following DBS. Structural atrophy in the hippocampus and midbrain structures has also been reported. However, findings on functional connectivity changes in non-motor cortical regions remain inconsistent. Study limitations include small sample sizes, variability in imaging techniques, and differences in assessment conditions.

Conclusions: While DBS produces measurable neuroimaging changes in PD patients, definitive conclusions regarding its effects on brain structure and function remain elusive. Future research with larger, well-controlled cohorts and standardized methodologies is necessary to clarify the impact of DBS beyond symptomatic relief.

Background: Pisa Syndrome (PS) is an abnormal postural deformity characterized by lateral trunk flexion leading to significant disability in patients with Parkinson's disease (PD). Botulinum toxin (BTX) and deep brain stimulation (DBS) have emerged as potential interventions.

Objectives: To systematically review the available evidence on the efficacy and safety of BTX and DBS in managing PS in patients with idiopathic PD.

Methods: A systematic review was conducted following PRISMA guidelines. PubMed and Embase were searched for studies reporting BTX or DBS interventions for PS in PD patients. Outcomes included lateral trunk flexion (LTF) angle, pain scores, and clinical scales assessing posture. Risk of bias was assessed using RoB-2, ROBINS-I, and JBI tools. Meta-analyses were performed using random-effects models for BTX-related outcomes.

Results: Sixteen studies comprising 113 patients with PD and PS were included. Of these, 96 patients received BTX injections and 17 underwent DBS. Pooled analysis of four BTX studies (n = 45) showed a significant reduction in LTF angle (MD: 5.94°; 95% CI: 1.05 to 10.84) and VAS pain score (MD: 3.36; 95% CI: 1.73 to 4.99). Among the 17 patients treated with DBS, 14 received subthalamic nucleus (STN) stimulation, and the remainder underwent PPN or GPi targeting. Improvement in trunk posture was observed in 13 (76%) DBS cases.

Conclusions: This review finds that BTX injections are safe and effective for managing PS in PD, showing consistent, although modest, benefits in reducing posture abnormalities and pain. DBS shows promise, particularly with STN targeting, but stronger evidence is needed to confirm its efficacy.

Background: Parkinson's disease and atypical parkinsonism are characterized by motor and non-motor symptoms. As the disease advances, planning for end-of-life (EoL) care becomes increasingly important. However, consensus-based European guidelines for advance care planning and documentation of EoL care preferences for parkinsonism are lacking. Understanding current documentation practices for EoL care across Europe is an essential first step towards formulating such guidelines.

Objectives: Provide an overview of the status of EoL care documentation in selected regions of Austria, Estonia, Germany, Greece, Italy and Sweden.

Methods: Individuals diagnosed with moderate to severe parkinsonism, participating in the PD_Pal trial were enrolled. We reviewed participants' electronic health records (EHRs) and other documentation (eg, advance directives kept at home). A questionnaire was used to extract information on documented EoL care preferences.

Results: One hundred eighty nine participants were included (n = 182 Parkinson's disease; n = 7 atypical parkinsonism). Documented EoL care preferences were identified in 70% of the participants in Germany, 21% in Austria, 17% in Sweden, 7% in Greece, 3% in Italy, and 0% in Estonia. Participants more frequently documented their EoL preferences in advance directives than in EHRs. The content of the documentation was largely general, with limited attention to parkinsonism-specific issues.

Conclusions: We found considerable variability in the presence of EoL care documentation across European regions. Public awareness and availability of advance directive templates likely contributed to the higher percentage of German participants with advance directives. These should be considered as best practices for enabling individuals with parkinsonism to document their preferences and receive care aligned with them.

Background: Movement disorders have recently emerged as important neurologic manifestations of the 22q11.2 microdeletion that affects nearly one in every 2000 live births.

Objective: We aimed to map the existing evidence regarding the spectrum, diagnosis and treatment, and etiopathogenesis of movement disorders associated with 22q11.2 microdeletion, highlight key gaps, and provide recommendations for future research.

Methods: We conducted a comprehensive search of MEDLINE, Embase, CENTRAL, and reference lists to identify relevant clinical and preclinical studies, and summarize data on clinico-pathologic features, risk factors, and pathophysiology of movement disorders associated with molecularly defined 22q11.2 microdeletions.

Results: Forty-three (clinical: n = 41/43, 95%; preclinical: n = 2/43, 5%) studies met eligibility criteria. Most clinical studies (35/41, 85%) involved adults, of which 51% (21/41) were case series/reports, and the remainder observational studies. Key findings included: (1) emphasis on parkinsonism but emerging evidence for multiple other motor phenotypes, (2) non-specific findings on routine neuroimaging, albeit with promising early results of certain modalities (eg, volumetric analyses, molecular imaging) and fluid-based biomarkers, particularly for parkinsonism, and (3) multifaceted etiologic and pathophysiologic processes beyond those attributable to medication side effects. Prevailing gaps include research design limitations, heterogeneity of diagnostic methods, and limited systematic data on etiopathogenesis and treatments.

Conclusions: Current evidence supports an expanding spectrum of motor phenotypes associated with 22q11.2 microdeletion, with emerging data reporting potentially useful clinical markers and non-drug-related risk modifiers and underlying mechanisms. Addressing prevailing gaps will require enhanced research designs with up-to-date diagnostic and genetic methodologies, robust preclinical models, and cross-disciplinary collaborations.