Movement Disorders最新文献

Background and objective: Memory impairment is a frequent and debilitating symptom in neurodegenerative disorders. The objective of this study was to provide proof-of-principle that deep brain stimulation during sleep can modify memory consolidation in people with Parkinson's disease depending on the stimulation frequency that is applied.

Methods: Twenty-four patients with Parkinson's disease who were treated with deep brain stimulation of the subthalamic nucleus were included in this single-blind pilot study. Six patients had to be excluded because of insomnia on the night of testing. Patients were randomized (1:1 ratio) to receiving either low frequency deep brain stimulation (4 Hz) or clinically used high frequency deep brain stimulation (130 Hz) during early non-rapid eye movement (NREM) sleep. The main outcome measure was overnight memory retention as measured by a validated declarative memory task.

Results: Patients receiving low frequency deep brain stimulation during early NREM sleep (n = 9, 4 females, mean age 61.1 ± 4.3 years) showed improved overnight memory retention (z = 2.549, P = 0.011). Patients receiving clinically used high frequency deep brain stimulation (n = 9, 2 females, mean age 62.2 ± 7.1) did not show any improvement (z = 1.023, P = 0.306) leading to a significant difference between groups (z = 2.214, P = 0.027). Stronger improvement in memory function was correlated with increased cortical low frequency activity after low frequency deep brain stimulation as measured by electroencephalography (ρ = 0.711, P = 0.037).

Conclusion: These results provide proof-of-principle that memory can be modulated by frequency-specific deep brain stimulation during sleep. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: The pentanucleotide (TTTCA) repeat expansion (exp) insertion, along with the accompanying (TTTTA)exp, causes familial cortical myoclonic tremor with epilepsy (FCMTE). The genotype-phenotype correlations and intergenerational instabilities related to (TTTCA)exp and (TTTTA)exp are still unclear.

Objective: The aim was to investigate the genotype-phenotype correlations and intergenerational instabilities related to (TTTCA)exp and (TTTTA)exp in FCMTE1.

Methods: We performed targeted long-read sequencing on 77 FCMTE1 patients. After quality control, metrics such as total repeat count, respective (TTTTA)exp and (TTTCA)exp count, and interruptions were assessed in 73 patients. Correlations between metrics and the patients' clinical features, as well as repeat instability during parental transmission, were analyzed.

Results: Among 73 alleles, the average total repeat counts were 848 ± 152 units, with (TTTTA)exp and (TTTCA)exp averaging 498 ± 196 units and 356 ± 110 units, respectively. (TTTCA)exp counts were inversely correlated with the age at onset for cortical tremor (Spearman's rho = -0.348, P = 0.005) and epilepsy (Spearman's rho = -0.424, P = 0.003). A negative correlation was found between (TTTCA)exp counts and relatively moderate seizure pattern with prodrome (odds ratio = 0.988, 95% confidence interval: 0.980-0.995, P = 0.002). During parental transmission, (TTTCA)exp counts increased significantly (P = 0.007), with maternal transmission showing a significantly larger increase compared to paternal transmission (P = 0.013).

Conclusion: The (TTTCA)exp insertion serves as the length-dependent pathogenic component within the two-motif repeat expansion. Its differential expanding nature during parental transmissions is highly associated with the genetic anticipation in FCMTE1. © 2024 International Parkinson and Movement Disorder Society.

Background: Population-scale databases majorly contribute to variant interpretation. The recently released Genome Aggregation Database (gnomAD) v4 offers a >5-fold increased sample size compared to v2.1.1. Pathogenic variants absent from v2.1.1 are now registered in v4 at a considerable rate. The implications on variant interpretation in dystonia are unknown.

Methods: All curated variants linked to the most common dominant forms of isolated dystonia were extracted from the International Parkinson's Disease and Movement Disorder Society Gene database. We compared variant population-frequencies and gene constraint metrics between gnomAD v2.1.1 and v4.

Results: The majority of dystonia-causing variants (192/247, 77.7%) remained absent from the newer gnomAD version. Of 219 variants absent from v2.1.1, 27 (12.3%) appeared for the first time in v4.1, including well-established pathogenic alleles. Gene constraints for GNAL and KMT2B significantly decreased in v4.

Conclusions: A growing number of dystonia-linked alleles are seen in gnomAD v4. The presence in population-scale data does not preclude pathogenicity. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: Depression is a common nonmotor complication in Parkinson's disease (PD). However, few studies have evaluated the efficacy of first-line psychological therapies for depression in this patient population.

Objectives: This randomized controlled trial evaluated the efficacy of interpersonal psychotherapy (IPT), an empirically validated intervention for depression that focuses on the bidirectional relationship between mood disturbance and interpersonal and social stressors. A secondary aim was to assess maintenance of treatment gains at 6-month follow-up.

Methods: Participants with PD stages I to III and a comorbid depressive disorder were randomly assigned to 12 sessions of IPT (n = 32) or supportive therapy (ST) (n = 31), our active control intervention. The primary outcome was the Hamilton Depression Rating Scale (HAM-D) administered blindly by telephone. Secondary outcomes included self-report depression and anxiety, quality of life, clinician-rated motor symptom, interpersonal relationships, and attachment style.

Results: IPT compared to ST resulted in a greater reduction in posttreatment HAM-D scores (least square mean difference = -3.77, 95% confidence interval [CI]: -6.19 to -1.34, P = 0.003) and was associated with a greater odds of meeting remission (odds ratio = 3.23, 95% CI: 1.10-9.51, P = 0.034). The advantage of IPT over ST on HAM-D scores and remission rates was not sustained at the 6-month follow-up. Both treatments improved self-report depression, anxiety, quality of life, and aspects of interpersonal functioning.

Conclusions: This trial demonstrates the benefits of acute treatment with IPT in reducing depressive symptoms in PD. Clinicians should consider psychotherapy, alone or in combination with medication, as an important treatment option for PD depression. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: Deep brain stimulation is a treatment for advanced Parkinson's disease and currently tuned to target motor symptoms during daytime. Parkinson's disease is associated with multiple nocturnal symptoms such as akinesia, insomnia, and sleep fragmentation, which may require adjustments of stimulation during sleep for best treatment outcome.

Objectives: There is a need for a robust biomarker to guide stimulation titration across sleep stages. This study aimed to investigate whether evoked resonant neural activity (ERNA) is modulated by sleep.

Methods: We recorded local field potentials from the subthalamic nucleus of four Parkinson's patients with externalized electrodes while applying single stimulation pulses to investigate the effect of sleep on ERNA.

Results: We found that ERNA features change with wakefulness and sleep stages and are correlated with canonical frequency bands and heart rate.

Conclusions: Given that ERNA modulates with sleep, it could be used as a robust marker for automatic stimulation titration during sleep. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: Dementia with Lewy bodies (DLB) commonly exhibits a complex neuropathology, sharing characteristics with Alzheimer's disease (AD), including tau aggregates. However, studies using the ¹⁸F-AV-1451 tau tracer have shown inconsistent findings regarding both the extent and topographical distribution of tau pathology in DLB.

Objectives: Our aim was to elucidate the topographical patterns of tau deposition in DLB and to investigate the in vivo pathological distinction between DLB and AD in virtue of the ¹⁸F-Florzolotau positron emission tomography (PET) imaging.

Methods: This cross-sectional study enrolled patients with DLB (n = 24), AD (n = 43), and cognitively healthy controls (n = 18). Clinical assessments and ¹⁸F-Florzolotau PET imaging were performed. ¹⁸F-Florzolotau binding was quantitatively assessed on PET images using standardized uptake value ratios and voxel-wise analysis.

Results: ¹⁸F-Florzolotau PET imaging revealed widespread tau deposition across various cortical regions in DLB, uncovering heterogeneous topographical patterns. Among patients, 54.17% showed patterns similar to AD, whereas 16.67% exhibited distinct patterns. Compared to AD, DLB exhibited a unique in vivo neuropathological profile, characterized by a lower tau protein burden, heterogeneous topographical distributions, and a specific role of the medial temporal lobe in tau pathology.

Conclusions: ¹⁸F-Florzolotau PET imaging elucidated tau pathology patterns in DLB, providing valuable insights for future in vivo pathological differentiation and potential disease-modifying therapies. © 2024 International Parkinson and Movement Disorder Society.