Journal of Movement Disorders最新文献

Objective: Access to care for people with Parkinson's disease (PD), particularly to device-aided therapies (DAT), is not equally distributed. The objective was to analyze accessibility to DAT (deep brain stimulation, intraduodenal levodopa pump therapy, and apomorphine pump therapy) in Poland.

Methods: We analyzed the distribution of DAT use in Poland by determining the number of persons with PD receiving one of the three DATs during 2015-2021.

Results: In 2021, the number of persons receiving DAT in Poland was 0.56% of the total PD population, increasing from 0.21% in 2015. Overall, deep brain stimulation was the preferred DAT in Poland, but strong regional differences in the use of the other DATs were observed. Accessibility to DAT was negatively associated with average annual income (p < 0.001).

Conclusion: Access to DAT for persons with PD in Poland is still limited, and strong regional differences in accessibility were observed, although its general increase over the last decade is encouraging.

Tubulin beta 4A class IVa (TUBB4A) spectrum disorders include autosomal dominant dystonia type 4 or hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC syndrome). However, in rare cases, only mild hypomyelination in the cortex with no basal ganglia atrophy may be observed. We report a case of a family with TUBB4A mutation and complicated hereditary spasticity paraplegia (HSP). We performed quadro whole-exome sequencing (WES) on the family to identify the causative gene of progressive spastic paraparesis with isolated hypomyelination leukodystrophy. We identified a novel TUBB4A p.F341L mutation, which was present in all three affected patients but absent in the unaffected father. The affected patients presented with adult-onset TUBB4A disorder, predominant spastic paraparesis with/without ataxia, and brain hypomyelination with no cognitive impairment or extrapyramidal symptoms. In the literature, HSP is considered a TUBB4A spectrum disorder.

Objective: A large body of literature has examined the links between the use of dopamine replacement therapy (DRT) in Parkinson's disease (PD) and the development of "impulsive-compulsive behaviors (ICBs)." Little is known regarding the link between the development of ICBs and health-related quality of life (HRQOL). We aimed to explore the factors that are associated with poorer HRQOL, especially in relation to DRT-induced ICBs, in a sample of PD patients.

Methods: This PARKADD (PARK: PARKinson's disease; ADD: behavioral ADDictions) study was a prospective case‒control study initially designed to assess the factors associated with ICBs in PD patients. A prospective clinical follow-up was added, aiming to capture the long-term evolution of HRQOL in relation to ICBs occurring or worsening after the beginning of PD. We focused on sociodemographic and PD characteristics and the history or presence of ICBs. HRQOL was measured using the Parkinson's Disease Questionnaire-8. A multivariate linear regression was performed to identify factors related to poorer HRQOL.

Results: A total of 169 patients were eligible for the follow-up study. The presence of an ICB, a higher levodopa equivalent daily dose (LEDD) and a longer PD duration were significantly associated with poorer HRQOL, with an interaction between LEDD and PD duration.

Conclusion: The presence of an ICB was related to poorer HRQOL and should be considered a crucial factor for the management of PD patients. Several studies were recently published that provide guidelines for the management of these patients, with recommendations based on two key principles: prevention and specific treatment.

Circadian disruption is being increasingly recognized as a critical factor in the development and progression of Parkinson's disease (PD). This review aims to provide an in-depth overview of the relationship between circadian disruption and PD by exploring the molecular, cellular, and behavioral aspects of this interaction. This review will include a comprehensive understanding of how the clock gene system and transcription-translation feedback loops function and how they are diminished in PD. The article also discusses the role of clock genes in the regulation of circadian rhythms, as well as the impact of clock gene dysregulation on mitochondrial function, oxidative stress, and neuroinflammation, including the microbiota-gut-brain axis, which have all been proposed as being crucial mechanisms in the pathophysiology of PD. Finally, this review highlights potential therapeutic strategies targeting the clock gene system and circadian rhythm for the treatment of PD.

Intracellular α-synuclein (α-syn) inclusions are a neuropathological hallmark of Lewy body disease (LBD) and multiple system atrophy (MSA), both of which are termed synucleinopathies. LBD is defined by Lewy bodies and Lewy neurites in neurons, while MSA displays glial cytoplasmic inclusions in oligodendrocytes. Pathological α-syn adopts an ordered filamentous structure with a 5-10 nm filament diameter, and this conformational change has been suggested to be involved in the disease onset and progression. Synucleinopathies also exhibit characteristic ultrastructural and biochemical properties of α-syn filaments, and α-syn strains with distinct conformations have been identified. Numerous experimental studies have supported the idea that pathological α-syn self-amplifies and spreads throughout the brain, during which processes the conformation of α-syn filaments may drive the disease specificity. In this review, we summarize the ultrastructural features and heterogeneity of α-syn filaments in the brains of patients with synucleinopathy and in experimental models of seeded α-syn aggregation.