Movement Disorders Clinical Practice最新文献

Background: Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder characterized by progressive spasticity and lower limb weakness. The most common forms of autosomal dominant HSP are caused by pathogenic variants in SPAST (SPG4 or HSP-SPAST), ATL1 (SPG3A or HSP-ATL1), and REEP1 (SPG31 or HSP-REEP1).

Objectives: We performed an MDSGene Systematic Review to determine in-depth genotype-phenotype associations and to estimate longitudinal progression, to inform prognostication and clinical trial stratification.

Methods: We systematically collected demographic, phenotypic, and genetic data from published reports of individuals affected by these forms of HSP using the MDSGene protocol.

Results: We reviewed 2177 affected individuals, including 1670 individuals with HSP-SPAST, 356 with HSP-ATL1 and 151 with HSP-REEP1. HSP-ATL1 was associated with an earlier age at onset compared to HSP-SPAST and HSP-REEP1. Toe-walking was more frequently reported in HSP-ATL1 (10.4%) and HSP-REEP1 (3.3%) than HSP-SPAST (0.3%). Upper limb hyperreflexia and abnormalities of bladder function were more frequent in HSP-SPAST than HSP-ATL1 or HSP-REEP1. Sufficient data was available to estimate disease progression for HSP-SPAST; this showed that Spastic Paraplegia Rating Scale (SPRS) scores increased with increasing age at examination after the age of 40 years. Truncating variants were more frequent in HSP-SPAST and HSP-REEP1 than HSP-ATL1.

Conclusion: Overall, HSP-ATL1, HSP-SPAST and HSP-REEP1 demonstrated differences in clinical phenotypes. To our knowledge, this is the first systematic review to model longitudinal progression using SPRS scores in HSP. Missing data is a limiting factor in all these comparisons, highlighting the need for uniform data collection. Online resources can be found at https://www.mdsgene.org/.

Background: Significant weight loss (SWL) is considered a common complication of Parkinson's disease (PD).

Objective: Our aim was (1) to compare the frequency of SWL in people with PD (PwP) vs. healthy controls (HC), (2) to identify predictors of SWL in PwP, and (3) to analyze the relationship between SWL and quality of life (QoL) and autonomy for activities of daily-living (ADL).

Methods: In this prospective 5-year follow-up population-based observational study, PwP and HC from the COPPADIS cohort with repetitive weight examinations over 5 years were included. A decrease >10% in weight at 5 years (V5) compared to baseline (V0) was defined as SWL. Regression models were applied to identify predictors of SWL.

Results: Mean weight decreased in PwP (N = 407; 61.9 ± 8.9 years old, 57% males) from 75.5 ± 13.2 at V0 to 73.8 ± 13.5 at V5 (P < 0.0001) but not in HC (N = 110; 61.9 ± 7.4 years old, 52.7% males; from 75.9 ± 13.8 at V0 to 76.3 ± 15.1 at V5 [P = 0.878]). The frequency of SWL was twice as high in PwP than in HC (18.2% [74/407] vs 9.1% [10/110]; P = 0.013). SWL at V5 was associated with a worse QoL and autonomy for ADL (P < 0.0001). To be older (P = 0.014) and an impairment from V0 to V5 in motor complications (UPDRS-IV) (P = 0.001) and mood (BDI-II) (P = 0.009) were associated with SWL in PwP.

Conclusion: SWL is frequent in PwP and is associated to a worse QoL and decreased autonomy for ADL.

Background: Although resting tremor is a characteristic feature of Parkinson's disease (PD), many patients also suffer from action tremor. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in reducing motor symptoms. However, it is unclear to what extent STN-DBS improves action tremor in PD, particularly kinetic tremor.

Objectives: Evaluate the effectiveness of STN-DBS on resting, postural, and kinetic tremor, with particular focus on kinetic tremor.

Methods: PD patients treated with bilateral STN-DBS were included. Patients with a score of ≥1 for tremor subtypes in either stimulation condition were included for tremor subtype analyses. The Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) was administered OFF-medication, for both the OFF- and ON-stimulation condition, 6-12 months post-surgery. Wilcoxon signed-rank tests were used and effect sizes calculated. In addition, sensitivity analyses and a systematic literature review was performed.

Results: 422 patients were included. For tremor subtype analyses, 251 patients were included for resting tremor amplitude, 270 for resting tremor constancy, 215 for postural tremor and 144 for kinetic tremor. DBS significantly improved all tremor subtypes (P < 0.001). Effect sizes were very large across tremor subtypes (Cohen's d > 1.00). Mean percentage improvement was comparable among resting (71.3%), postural (64.6%), and kinetic (65.1%) tremor. Similarly, the proportion of patients experiencing complete bilateral tremor resolution was consistent across tremor subtypes, 50.2% for resting, 55.8% for postural, and 51.4% for kinetic tremor.

Conclusions: Bilateral STN-DBS appears to improve all tremor subtypes in PD equally, including postural and kinetic tremor.

Background: Responsiveness and minimal clinically important difference (MCID) are among the psychometric properties necessary for interpreting results. However, responsiveness and MCID of the Falls Efficacy Scale-International (FES-I) and the Biodex Balance System (Biodex-BS) in individuals with Parkinson's disease (PD) have not yet been determined.

Objectives: The objective of this study is to establish the responsiveness and MCID of FES-I and Biodex-BS, as well as Berg Balance Scale, Time up and Go (TUG) test, Tinetti Gait and Balance Scale (TGBS), and Mini-Balance Evaluation Systems Test in PD.

Methods: In this prospective observational cohort study, 86 individuals with PD were assessed. Responsiveness was evaluated utilizing 11 predefined hypotheses. MCID was calculated using anchor and distribution-based methods. In this study, the Global Rating of Change-Patient (GRC-P) and Global Rating of Change-Therapist (GRC-T) and the Activity-Specific Balance Confidence Scale (ABC) were used as anchors. ROC analysis was utilized in the anchor-based method.

Results: The Fall Risk Test-Overall Stability Index (FRT-OSI), one of the Biodex-BS parameters, showed the highest responsiveness. TUG and FES-I indicated a substantial responsiveness, while the TGBS demonstrated the lowest responsiveness. MCID of FRT-OSI, which had the highest responsiveness, had 0.78 with the distribution-based method. In the anchor-based method, MCID with GRC-P, GRC-T, and ABC anchors were 0.54, 0.95, and 0.54, respectively.

Conclusions: FRT-OSI demonstrated the highest responsiveness in PD. TUG and FES-I may be used as alternatives when a Biodex-BS is inaccessible. TGBS clinical utility may be limited. MCIDs determined in this study may help interpret the clinical importance of the results.

Background: Pain is one of the most disabling non-motor symptoms in adult-onset isolated dystonia (AOID). The Pain in Dystonia Scale (PIDS) was developed and validated in cervical dystonia. Its applicability to other focal subtypes remains unknown.

Objectives: To validate the PIDS in patients with craniofacial and upper limb dystonia, expanding its use beyond cervical dystonia.

Methods: We conducted a two-phase cross-sectional validation study in independent cohorts from Calgary, Canada and Italy. The Calgary pilot cohort (n = 20) included participants with craniofacial and/or upper limb dystonia who completed the PIDS twice for test-retest reliability and a battery of comparator scales. The Italian cohort (n = 109) was recruited through the Italian Dystonia Registry and completed the PIDS after cross-cultural adaptation. Internal consistency, test-retest reliability, construct validity, and distribution properties were assessed using established psychometric standards.

Results: Pain was highly prevalent (90.0% Calgary; 96.3% Italy), with anatomical distribution varying by dystonia subtype. Internal consistency was high across both cohorts (Cronbach's alpha 0.82-0.96), with minimal floor and ceiling effects. Test-retest reliability in the pilot cohort was excellent (ICC = 0.85). Construct validity was supported by strong correlations between PIDS scores and established pain and quality-of-life measures. Functional impact and pain modulators were consistently reported across cohorts, with stress identified as the most frequent aggravating factor and rest and stretching as common relieving factors.

Conclusions: The PIDS demonstrates reliability, validity, and feasibility in craniofacial and upper limb dystonia, supporting its adoption for evaluating dystonia-related pain in clinical and research settings across the main focal subtypes.

Background: Orthostatic tremor (OT) and orthostatic myoclonus (OM) are rare hyperkinetic disorders characterized by unsteadiness during stance. Substantial clinical overlap limits the prognostic and therapeutic value of categorical diagnostic labels.

Objectives: To assess whether a multidomain disease burden framework provides more meaningful stratification than traditional OT/OM diagnoses and to identify phenotypic subgroups.

Methods: We conducted a cross-sectional analysis of 58 patients with OT/OM who underwent multidomain assessment. A composite Disease Burden Score (DBS) was derived from five domains: symptom severity, functional limitation, comorbidity burden, medication exposure, and fall risk. Patients were classified into high- and low-burden groups. Predictors of high disease burden were evaluated using Firth logistic regression and random forest classifiers. Latent class analysis (LCA) identified subgroups, and concordance between DBS strata and latent classes was assessed. Exploratory k-means and hierarchical clustering were performed for validation.

Results: DBS stratification distinguished high- and low-burden patients with strong accuracy (AUC = 0.96). All five domains contributed to burden classification, although individual regression coefficients were imprecise. LCA identified four subgroups: low-burden, functionally impaired, comorbidity-dominant, and globally burdened. These subgroups did not align with OT/OM diagnostic categories. Concordance between LCA classes and DBS strata was weak (Cramer's V = 0.176). Demographic variables and SF-36 quality-of-life domains did not differ across latent classes.

Conclusion: Multidomain clinical data enable disease-burden stratification and reveal phenotypic heterogeneity in orthostatic movement disorders. Limited correspondence with traditional diagnoses supports a spectrum-based model. DBS and LCA offer complementary frameworks for individualized assessment, warranting validation in larger and longitudinal cohorts.