Movement Disorders最新文献

Background: Temporal interference stimulation (TIS) is a novel noninvasive electrical stimulation technique to focally modulate deep brain regions; a minimum of two high-frequency signals (f₁ and f₂ > 1 kHz) interfere to create an envelope-modulated signal at a deep brain target with the frequency of modulation equal to the difference frequency: Δf = |f₂ - f₁|.

Objective: The goals of this study were to verify the capability of TIS to modulate the subthalamic nucleus (STN) with Δf and to compare the effect of TIS and conventional deep brain stimulation (DBS) on the STN beta oscillations in patients with Parkinson's disease (PD).

Methods: DBS leads remained externalized after implantation, allowing local field potentials (LFPs) recordings in eight patients with PD. TIS was performed initially by two pairs (f₁ = 9.00 kHz; f₂ = 9.13 kHz, 4 mA peak-peak per pair maximum) of scalp electrodes placed in temporoparietal regions to focus the envelope signal maximum (Δf = 130 Hz) at the motor part of the STN target.

Results: The comparison between the baseline LFPs and recordings after TIS and conventional DBS sessions showed substantial suppression of high beta power peak after both types of stimulation in all patients.

Conclusions: TIS has the potential to effectively modulate the STN and reduce the beta oscillatory activity in a completely noninvasive manner, as is traditionally possible only with intracranial DBS. Future studies should confirm the clinical effectiveness of TIS and determine whether TIS could be used to identify optimal DBS candidates and individualize DBS targets. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Objective: Low-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been associated with positive effects on verbal fluency (VF) in patients with Parkinson's disease. This prospective study investigates stimulation direction-dependent and site-specific effects of theta frequency DBS on VF.

Methods: In a double-blind, cross-over design (n = 20), we tested VF during left subthalamic theta stimulation (stimulation-off, omnidirectional, and threedirectional stimulation conditions). DBS electrode localization and electric field calculations were performed (n = 18). Probabilistic sweet spot mapping identified voxels with significant change in VF.

Results: Best directional stimulation improved VF performance significantly compared with the stimulation-off and omnidirectional stimulation condition. This effect followed a medial-to-anterolateral gradient with higher VF improvement observed on the border between the motor and associative subparts of the STN.

Conclusion: We provide first proof-of-principle evidence that directional theta frequency DBS improves VF, possibly related to stimulation of the anterolateral STN. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Objectives: To investigate trajectories of regional brain volume changes in multiple system atrophy (MSA) and their potential utility as surrogate markers of disease progression in the cerebellar subtype (MSA-C).

Background: Reliable biomarkers for tracking disease progression in MSA are urgently needed. Although several studies have explored neuroimaging markers, imaging measures that are reliable and reproducible at the individual-level are lacking.

Methods: Longitudinal three-dimensional (3D)-T1 images from multiple cohorts of 21 subjects with probable MSA-C, 19 with probable MSA-parkinsonian subtype (MSA-P), 113 with Parkinson's disease, and 227 healthy controls were processed using the FreeSurfer longitudinal pipeline. Extracted volumes were assessed for individual longitudinal trajectories, intra-individual variability, and pontine regional volume decline.

Results: Pontine volumes showed lower intra-individual variability in measurements compared with other infratentorial brain regions. All probable MSA-C patients exhibited a decline in pontine volume, ranging from -3.6% to -16.8% per year (mean: -9.1%), falling more than two standard deviations below the mean of healthy controls. In MSA-C, the temporal dynamics of pontine volumes exhibited nonlinear changes, characterized by progressive atrophy in the earlier period of the disease, followed by a pre-plateau phase associated with advanced disability in the later period. Predictive modeling suggests that pontine atrophy may begin before symptom onset of MSA-C.

Conclusions: Pontine volume is a sensitive marker of disease progression, exhibiting a nonlinear decline with low intra-individual variability in measurements and greater volume loss in the earlier stages, reaching a pre-plateau phase in the later stages with advanced disability. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: Epidural electrical spinal cord stimulation has been studied for more than a decade for Parkinson's disease symptoms, but compelling evidence for its effectiveness is still lacking.

Objective: The aim of this study was to evaluate the effectiveness of spinal cord stimulation in Parkinson's disease.

Methods: Participants had Parkinson's disease diagnosis, gait impairment and freezing of gait, and no pain. Paddle electrodes were implanted at the T2-T4 level. After 6 months of parameter selection, subthreshold and sham stimulation were compared through a double-blinded randomized evaluation and further compared with suprathreshold stimulation. A second 6- to 8-month period of parameter adjustment and a final long-term open evaluation followed. Outcomes were determined via Timed Up and Go (TUG), Movement Disorders Society Unified Parkinson's Disease Scale (MDS UPDRS) Part III, Mini BESTest, New Freezing of Gait Questionnaire, Parkinson's Disease Questionnaire 39, Fall Efficiency Scale International, and accelerometer-based gait analysis. Functional magnetic resonance imaging was also performed during the double-blind evaluation period.

Results: This study was terminated for futility after eight patients underwent implantation and seven completed double-blind evaluations. TUG duration ON stimulation was median 11.59 (19.7-10.9) seconds on medication and 24.49 (48.1-13.7) seconds off medication, which was not statistically different from sham with 12.38 (13.7-11.8) and 16.93 (30-14.4) seconds on respective medication status. Likewise, no significant differences were found for MDS UPDRS Part III scores, respectively, ON active stimulation for 29 (33.5-23) and 42 (51-40) seconds and on sham 28 (30.5-26) and 50 (51.5-44) seconds. No effect from stimulation was identified in any other outcome.

Conclusions: No effect of spinal cord stimulation in Parkinson's disease symptoms was identified. © 2025 International Parkinson and Movement Disorder Society.

Background: Motor cortex disinhibition, as measured by impaired short-interval intracortical inhibition (SICI) using transcranial magnetic stimulation (TMS), is a well-established feature of Parkinson's disease (PD). However, its substantial variability among patients remains unexplained, prompting questions about its origin, clinical relevance, and connection to disease heterogeneity.

Objective: Based on biological links between olfaction and motor function, we aimed to investigate the possible relationship between motor cortex disinhibition and olfactory dysfunction in PD.

Methods: We assessed motor cortex disinhibition, as measured by SICI, and olfactory dysfunction, as measured by the Sniffin' Stick Test 12 items (SST-12), in a new cohort of early-to-mid-stage PD patients (n = 45) and age-matched and gender-matched healthy controls (n = 35).

Results: We obtained moderate-to-extreme Bayesian evidence that patients had the expected decrease of cortical inhibition and decrease of olfactory function, with neither feature correlating with the clinical motor severity. Cortical disinhibition and olfactory dysfunction were correlated, with strong-to-extreme evidence, both considering all subjects (n = 80), only healthy controls (n = 35), only patients (n = 45), or only levodopa-naïve patients (n = 20). We tested and excluded age as a possible confounding factor. The evidence from causal inference analysis supported a mediation role of PD that aligned more with an internal pathogenic mechanism than with an external one.

Conclusion: These findings suggest that motor cortex disinhibition and olfactory dysfunction might be linked by a common early pathogenic process in PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: Spinocerebellar ataxia 27A (SCA27A) is a rare neurodegenerative disorder characterized by childhood-onset tremor and progressive cerebellar dysfunction. SCA27A is usually caused by loss-of-function FGF14 variants.

Objectives: We report the identification of a novel FGF14 variant in a five-generation family with autosomal dominant ataxia and describe the clinical phenotype and response to subthalamic nucleus deep brain stimulation (STN-DBS) and 4-aminopyridine (4-AP).

Methods: Whole genome sequencing was performed on the proband, two affected sisters (Patients 2 and 3), and one unaffected sister (III5). Sanger sequencing was performed to confirm the variant and sequence additional family members.

Results: A novel heterozygous in-frame deletion (p.Val119del) in FGF14 was identified in this family affected by childhood-onset tremor followed by late-onset progressive ataxia. Two patients showed significant tremor reduction following STN-DBS and balance improvement with 4-AP.

Conclusions: We identified a novel likely pathogenic FGF14 variant segregating in a family with SCA27A. Additionally, we suggest STN-DBS and 4-AP as promising treatment options for this condition. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: Bridge-like lipid transfer proteins (BLTPs) mediate bulk lipid transport at membrane contact sites. Mutations in BLTPs are linked to both early-onset neurodevelopmental and later-onset neurodegenerative diseases, including movement disorders. The tissue specificity and temporal requirements of BLTPs in disease pathogenesis remain poorly understood.

Objective: The objective of this study was to determine tissue-specific and aging-dependent roles for VPS13A and BLTP2 using Drosophila models.

Methods: We generated tissue-specific knockdowns of the VPS13A ortholog (Vps13) and the BLTP2 ortholog (hobbit) in neurons and muscles of Drosophila. We analyzed age-dependent locomotor behavior, neurodegeneration, and synapse development and function.

Results: Neuron-specific loss of the VPS13A ortholog caused neurodegeneration followed by aging-dependent movement deficits and reduced lifespan, whereas muscle-specific loss affected only lifespan. In contrast, neuronal loss of the BLTP2 ortholog resulted in severe early-onset locomotor defects without neurodegeneration, whereas muscle loss impaired synaptogenesis and neurotransmission at the neuromuscular junction.

Conclusions: VPS13A maintains neuronal survival, whereas BLTP2 orchestrates synaptic development. The phenotypic specificity of BLTP function provides mechanistic insights into distinct disease trajectories for BLTP-associated disorders. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: Cognitive impairment in Parkinson's disease (PD) is a key non-motor complication during the disease course.

Objectives: A review of detailed cognitive instruments to detect mild cognitive impairment (PD-MCI) or dementia (PDD) is needed to establish optimal tests that facilitate diagnostic accuracy.

Methods: We performed a systematic literature review of tests that assess memory, language including premorbid intelligence, and visuospatial domains (for tests of attention and executive functions see accompanying review) to determine suitability to assess cognition in PD. Based on in-depth scrutiny of psychometric and other relevant clinimetric properties, tests were rated as "recommended," "recommended with caveats," "suggested," or "listed" by the International Parkinson and Movement Disorder Society (IPMDS) panel of experts according to the IPMDS Clinical Outcome Assessment Scientific Evaluation Committee guidelines.

Results: We included 39 tests encompassing 48 outcome measures. Seven tests (different versions or subtests of the test counted once) were recommended, including four for memory, one for visuospatial domains, one for language (including three measures), and one for estimated premorbid intelligence. Furthermore, 10 tests (12 measures) were "recommended with caveats," 11 were "suggested," and 11 (15 measures) were "listed."

Conclusions: Recommended neuropsychological tests in memory, visuospatial functions, and language are proposed to guide the assessment of cognitive impairment and its progression in PD-MCI and PDD, and for use in clinical trials to stratify participants or as outcome measures. Novel measures being developed will need extensive validation research to be "recommended." © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.