Parkinson's Disease Patients Research Articles

COMPARING DIRECTIONAL AND OMNIDIRECTIONAL DEEP BRAIN STIMULATION IN PARKINSON'S DISEASE PATIENTS.

In 2015, directional leads have been released in Europe for deep brain stimulation (DBS) and have been particularly used for subthalamic nucleus (STN) DBS for Parkinson's disease (PD). In this study we aimed to compare an omnidirectional and directional leads cohort of PD patients when it comes to clinical effectiveness and to assess the correlation with volume of tissue activated - target overlap (VTA-target). A total of 60 consecutive patients were retrospectively included. 27 patients with bilateral directional leads were compared to 33 patients with bilateral omnidirectional leads. MDS-UPDRS part III scores, levodopa equivalent daily dose (LEDD), and VTA overlaps using both motor STN region and motor improvement sweetspot volume were compared at 12 months after surgery. There is a significantly higher LEDD reduction in the directional leads group (51.3 % reduction vs 42.7% reduction, p= 0.042) when compared to the omnidirectional group, with similar MDS-UPDRS III motor scores at 12 months. Omnidirectional leads patients had a significantly superior VTA-motor STN overlap volume than directional leads patients (32.01 mm3 vs 20.38 mm2, p = 0.0226). In directional leads patients, LEDD reduction was correlated to VTA overlap with the overall motor improvement mean map sweetspot (R = 0.36, p = 0.036), which was not the case for omnidirectional leads patients (R = 0.11, p = 0.276). Forty one percent of patients implanted with directional leads had a directional stimulation setting at 12 months, compared to thirty three percent at 3 months follow up. In directional leads patient's subgroup analysis, there was no significant difference in MDS UPDRS III scores, LEDD reduction, VTA overlaps with motor STN or overall motor improvement mean map sweetspot between patients stimulated omnidirectionally and directionally at 12 months. At 12 months, when compared to omnidirectional leads, directional leads manage with smaller VTA-target overlaps to obtain comparable MDS-UPDRS III scores with greater LEDD reduction in STN DBS for PD patients.

Influence of parkinson's disease on complications and revisions in total hip and knee arthroplasty: insights from a matched pair analysis.

The outcome of elective total joint arthroplasty (TJA) in patients with Parkinson's disease (PD) is controversial due to the concomitant risk profile. This study investigated postoperative complications and revision rates following total hip (THA) and knee arthroplasty (TKA) in patients with PD. Ninety-six patients with PD undergoing THA or TKA were matched 1:1 with non-PD patients using propensity score matching for age, sex and comorbidity (Charlson Comorbidity index, CCI). Rates of revisions, medical and surgical complications were compared. Univariate and multivariate regression analyses were calculated. PD patients exhibited higher rates of revision-surgeries within 90days (13.5% vs. 5.2%; p = 0.048), medical complications (68.8% vs. 43.8%; p < 0.001) and surgical complications (40.6% vs. 21.9%; p = 0.005). Multivariate regression analysis confirmed PD as a significant risk factor for complications and long-term revision-surgeries. PD increases the risk of adverse outcomes following THA and TKA. Improvements in pre-operative planning and post-operative care are critical to the improvement of outcomes in this vulnerable population.

Impact of diabetes mellitus type two on incidence and progression of Parkinson's disease: a systematic review of longitudinal patient cohorts.

Parkinson's disease (PD) is a chronic neurodegenerative disease of the elderly. Patients suffer from progressive motor and non-motor symptoms. Further, PD patients often present geriatric features like multimorbidity and polypharmacotherapy. A frequent comorbidity of PD patients is diabetes mellitus type two (T2DM). In the last decade growing evidence emerged on the impact of T2DM on PD. Of the present review was to analyze the impact of T2DM on PD incidence and progression in patient cohorts. A systematic review of the literature was performed via PubMed and Google Scholar. Studies on longitudinal PD patient cohorts with at least 10 patients per group were included. The diabetic state of the patient had to be determined. In total, 15 studies were analyzed for this review. According to most of the included studies T2DM increases the risk of developing PD significantly. Disease progression is augmented by T2DM both for motor and cognitive impairments. Some studies also point out a correlation of motor worsening and diabetic status measured by the serum HbA1c level. In relation to biomarkers, PD patients with diabetes have higher neurofilament light chain and Tau level but lower Amyloid beta level. T2DM seems to be a risk factor for the development and progression of PD. PD patients should be screened for T2DM and treatment should be initiated promptly. There is still a lack of knowledge about the molecular mechanisms leading to interactions of these diseases.

Comprehensive assessment of caregiver burden and strain in early-stage Parkinson's disease: An exploratory study.

Parkinson's Disease (PD) is a progressive neurodegenerative disorder affecting motor and cognitive functions, reducing the quality of life (QoL) for both patients and caregivers. This study explored correlations between clinical and psychological factors in early-stage PD patients and their caregivers, focusing on disease burden and caregiver stress. Nineteen PD patients and their caregivers were assessed. For patients, we evaluated disease severity (Hoehn and Yahr), cognitive functions (Montreal Cognitive Assessment, MoCA), anxiety levels (Hamilton Rating Scale for Anxiety, HRS-A), and quality of life (Parkinson's Disease Questionnaire, PDQ-39). For caregiver, we assessed caregiver burden (Caregiver Burden Inventory, CBI), functional social support (Family Strain Questionnaire, FSQ), and anxiety level (HRS-A). Spearman's correlation analyzed relationships between patient factors and caregiver burden. Cognitive impairment (MoCA) negatively correlated with patient QoL (PDQ-Cogn; r = -0.48, p = 0.04). Caregiver anxiety (HRS-A) was positively correlated with physical (r = 0.65, p = 0.003) and emotional stress (r = 0.57, p = 0.01), and higher family stress (FSQ). Our study highlights the complex relationships between clinical and psychological factors in PD patients and their caregivers. This supports the need for integrated approaches that address the clinical management of PD and the caregivers' psychological well-being.

Parkinson's disease and deep brain stimulation of the subthalamic nucleus (STN-DBS): long-term disease evaluation and neuropsychological outcomes in a 9-year matched-controlled study.

Matched-controlled long-term disease evaluation and neuropsychological outcomes derived from deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson´s disease (PD) are lacking, with inconsistent results regarding the cognitive impact of this procedure. Here we study the long-term effects associated to DBS comparing outcomes with a matched control group. A prospective observational study of 40 patients with PD with bilateral STN-DBS, with a mean follow-up of 9 (6-12) years was conducted. Disease evaluation was performed using the UPDRS-III, UPDRS-II, Hoehn-Yahr, and Schwab-England scales. Neuropsychological assessments were achieved utilizing the MMSE, DRS, RAVLT, BVRT, Stroop, and verbal fluency tests. A control group was used for comparison. Statistical analysis was performed with SPSSv.26. 40 patients were included, with a mean age of 62.8 ± 8.5 at the time of intervention. An improvement in motor symptoms of 48.6% (p < 0.001) and a reduction in LED of 58.6% (p < 0.001) was observed. No significant differences were observed in the MMSE (p = 0.414), DRS (p = 0.251), memory or interference assessments. A worsening in the construction subscale of DRS (p < 0.05) and in verbal fluency (phonemic and semantic) (p < 0.05) was observed. A head-to-head comparison showed significant differences between groups. An age ≤ 60 years was associated with a good long-term clinical prognosis (p = 0.019;OR = 6.75). STN-DBS is an effective and safe therapeutic option for the control of motor symptoms. However, it is associated with a selective deterioration in some cognitive functions in the long term. This study comprehensively evaluates STN-DBS in Parkinson´s disease in the long term, with findings that should be considered when indicating surgery in PD patients.

Delirium after deep brain stimulation for Parkinson's disease: a meta-analysis of incidence and risk factors.

Deep brain stimulation (DBS) is a valuable treatment for Parkinson's disease (PD), but postoperative delirium (POD) is a common complication. Understanding the risk factors for POD is crucial for optimizing patient selection and developing preventative measures. This systematic review and meta-analysis aims to identify predictors of POD in PD patients undergoing DBS surgery. We conducted a comprehensive search of four major databases for cohort studies on POD in patients undergoing DBS for PD, up to June 2024. Two reviewers independently screened studies, assessed the risk of bias using the Newcastle-Ottawa Scale, and extracted data. Meta-analysis was conducted using Review Manager, with heterogeneity assessed the I2 statistic and chi-square p value. Subgroup and sensitivity analyses were also performed to explore the consistency of findings. Eleven studies, including 1,368 patients, were analyzed to determine the incidence of POD in PD patients undergoing DBS. The incidence of POD in PD patients undergoing DBS, which was found to be 21% (95% CI: [14.6%, 27.4%]). Age, Mini-Mental State Examination (MMSE), and Non-Motor Symptom Scale (NMSS) were significant predictors, with effect sizes of (OR = 1.10, 95% CI: [1.06, 1.15], P < 0.00001), (OR = 0.85, 95% CI: [0.72, 1.00], P = 0.05), and (OR = 1.01, 95% CI: [1.00, 1.02], P = 0.04), respectively. However, gender, UPDRS-III ON score, brain atrophy, diabetes, Hamilton Anxiety Score (HAMA), operation time, disease duration, BMI, and cerebral infarction were not significant predictors. This meta-analysis suggests that age, cognitive function, and non-motor symptoms are important factors associated with POD patients undergoing DBS surgery. Further research with larger sample sizes and diverse populations is needed to confirm these findings and identify more specific predictors.

Fear of falling impairs spatiotemporal gait parameters, mobility, and quality of life in Parkinson's disease: a cross-sectional study.

Fear of Falling (FOF) significantly affects Parkinson's Disease (PD) patients by limiting daily activities and reducing quality of life (QoL). Though common in PD, the relation between FOF, mobility, and QoL remains unclear. This study examines the connections between FOF, gait, daily motor activity, and QoL in PD patients. Fifty PD patients on stable levodopa therapy were enrolled, excluding those with dementia or walking impairments. Assessments included UPDRS-III, Hoehn and Yahr, MoCA, Berg Balance scale, Geriatric Depression Scale and Fall Efficacy Scale International (FES-I). QoL was evaluated using PDQ39. The Timed-Up-and-Go (TUG) test was performed at regular and fast paces, with data collected via smartphone apps for TUG gait parameters and for 24-h quantity of movement monitoring (Activity Index, AIX). A subgroup of 10 patients also underwent 24-h gait monitoring. FOF was found in 38% of patients, correlating with worse motor scores and QoL (UPDRS-III, 26 vs 17, p < 0.0001; PDQ39 36 vs 14, p < 0.0001). FOF patients showed slower walking (0.73m/s vs 1.13m/s, p < 0.001), reduced step length (0.151 vs 0.220m, p < 0.001), and poorer adaptation to fast walking and environment (being unable to vary their speed and frequency). FOF and sex were both associated with a reduced mobility QoL, with a significant contribution of AIX only in women (r -0.648, p = 0.012). This study supports the existence of a significant correlation between FOF, motor activity and QoL in PD, especially in women, emphasize the need for targeted interventions, early rehabilitation and prospective studies focusing on gender.

Association between Parkinson's disease and risk of colorectal cancer: A systematic review and meta‐analysis

AbstractThis study aims to investigate the relationship between Parkinson's disease (PD) and colorectal cancer (CRC) risk by a systematic review and meta‐analysis. Using Embase, Pubmed, and Cochrane Library databases, 21 articles reporting clinical data of 1,635,873 PD patients and 10,388,842 healthy individuals were finally included. Based on the results of pooled analysis, we found that PD patients exhibited a decreased risk of CRC (relative risk (RR) = 0.74; 95% confidence interval (CI), 0.68–0.80). In contrast to case‐control (RR = 0.80; 95% CI, 0.64–1) and cohort studies (RR = 0.72; 95% CI, 0.66–0.79), the combined risk of PD patients with CRC in Asian nations (RR = 0.67; 95% CI, 0.58–0.78) was lower than that in Western countries (RR = 0.76; 95% CI, 0.70–0.82). In comparison to rectal cancer (RR = 0.82; 95% CI, 0.69–0.97), PD patients exhibited a lower combined risk of colon cancer (RR = 0.76; 95% CI, 0.67–0.86). Furthermore, the combined CRC risks for patients in studies published before 2010 and after 2010 were 0.76 (RR = 0.76; 95% CI, 0.66–0.88) and 0.74 (RR = 0.74; 95% CI, 0.68–0.80), respectively. These findings indicate that patients with PD had a reduced risk of CRC. Future studies are merited in exploring pathological molecular linkages or underlying mechanisms of inverse association between CRC and PD.

In Vivo UV-Induced Fluorescence Spectroscopy of Skin in Parkinson's Disease.

Characteristic patterns of UV-induced skin autofluorescence were determined for patients with Parkinson's disease (PD) and associated with dysmetabolic alterations, such as nonenzymatic protein glycation, an increase in extracellular matrix stiffness, impaired metabolism of tissue fluorophores, mitochondrial dysfunction, and accumulation of aberrant proteins. Key differences in skin autofluorescence spectra were for the first time observed in PD, making it possible to discriminate between PD patients and healthy persons or individuals without signs of chronic neurodegeneration. Namely, skin fluorescence related to the reflected signal upon excitation with UV light at 375 nm was lower in PD patients.

What does it mean when the pleasant smells come and go? Correlation between UPSIT odor identification status and fluctuation of non-motor symptoms in Parkinson's disease.

Parkinson's disease (PD) is characterized by motor and non-motor symptoms, including olfactory dysfunction. Prior studies have shown that olfaction deteriorates with disease progression, however fluctuations in olfaction and related PD symptoms have been less explored. This study aimed to investigate correlations between changes in odor identification ability and PD symptoms. PD patients recruited from Taichung Veterans General Hospital underwent at least two consecutive Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and University of Pennsylvania Smell Identification Test (UPSIT) evaluations. The patients were grouped based on changes in olfactory identification ability between evaluations, and fluctuations in PD symptoms were compared between groups. Ninety-seven PD patients with 114 complete sets of data were analyzed. Significant divergent results were observed between changes in five MDS-UPDRS non-motor subscores and the conversion status of five pleasant odors, including anxiety vs. bubble gum, apathy vs. banana, dizziness vs. coconut, urination vs. root beer, and dopamine dysregulation syndrome (DDS) vs. grape. Fluctuations in the ability to detect pleasant odors, may have a complex interaction with other non-motor symptoms, including in the neurobehavioral and autonomic domains. Serial monitoring of olfactory function, particularly with pleasant odors, may provide valuable insights for tracking non-motor symptoms in PD and warrants further investigation into their therapeutic implications.

Novel Objective Tool to Assess Tremor Reveals Unilateral Focused Ultrasound Improves Tremor Bilaterally.

Tremor in essential tremor and in tremor-dominant Parkinson's disease is assessed by subjective observations in patients undergoing focused ultrasound thalamotomy, a minimally invasive procedure intended to alleviate tremor in these patients. To develop an objective tool for tremor analysis to be used before and after focused ultrasound thalamotomy treatment in the treated hand (contralateral to ablation) and non-treated (ipsilateral to ablation). Using image processing and signal processing that utilized images of a Archimedes spiral drawing, we created a tool to analyze tremor. First, we showed that the proposed tool reproduces known clinical dynamics on the treated hand, and then we used it to evaluate the clinical dynamics on the non-treated hand. Using the tool we developed, we were able to demonstrate a significant reduction in tremor following focused ultrasound thalamotomy among 132 essential tremor and 26 tremor-dominant Parkinson's disease patients in the treated hand using drawings of Archimedes spirals up to 1 year following the procedure. Thus, we reproduced known clinical data and therefore validated the proposed tool. In addition, we were able to demonstrate a significant improvement in the non-treated hand as well as a significant deterioration in the efficacy of focused ultrasound thalamotomy over time. Our objective method, which incorporated image processing and signal processing, provided a quantitative measure of tremor reduction following focused ultrasound thalamotomy. It demonstrated significant improvement in tremors in the treated and non-treated hands following focused ultrasound thalamotomy as well as deterioration in the efficacy of treatment over time. If replicated in other studies, this method may complement current subjective assessments.

Disrupted Paraventricular Hypothalamic Nucleus Functional Connectivity in Parkinson's Disease With Constipation.

Constipation is one of the most common non-motor symptoms in patients with Parkinson's disease (PD), which could manifest during the early stage of the disease. However, the etiology of constipation in PD remains largely unknown. Previous studies supported that gastrointestinal dysfunction may be associated with functional connectivity alterations in paraventricular hypothalamic nucleus (PVN). Therefore, this study aimed to investigate the potential contribution of the PVN to the pathogenesis of constipation in a cohort of early-stage patients with PD and to compare brain network organization between PD patients with and without constipation. A total of 66 PD patients (PD with constipation and without constipation) and 30 healthy controls were prospectively enrolled. All participants acquired T1-weighted and resting-state fMRI scans. Then we employed voxel-based morphometry analysis and functional connectivity analysis. We observed a decreased functional connectivity in the PVN-pontine tegmentum pathway in PD patients with constipation compared to the patients without constipation (p = 0.006, t = 5.37), while we did not find any changes in basal ganglia circuitry between these two groups. In addition, we found that the functional connectivity between PVN and pontine tegmentum was negatively associated with the UPDRS I, II, III and NMSS scores (p < 0.05). Meanwhile, these two types of patients also showed substantial differences in functional connections linking the inferior frontal gyrus and cerebellum with multiple brain regions. We discovered no statistical difference in gray matter volume among these two groups. Our study provides further insights into the dysfunctional mechanisms of constipation, suggesting that abnormal PVN functional connectivity may be related to the mechanism of constipation in PD. Meanwhile, the inferior frontal gyrus and cerebellum may be involved in the occurrence of constipation in PD patients.

Investigation of the validity, reliability and psychometric properties of the Turkish version of the Ottawa sitting scale in patients with Parkinson’s disease

The Ottawa Sitting Scale is a tool for the multidimensional assessment of sitting balance. This study aimed to investigate the validity, reliability, and psychometric properties of the Turkish version of the Ottawa Sitting Scale (OSS-TR) in Turkish-speaking patients with Parkinson’s disease (PD). The study included 56 patients diagnosed with PD based on the UK Brain Bank Criteria. Construct validity of the OSS-TR was established through the evaluation of structural and convergent validity. Explanatory factor analysis and confirmatory factor analysis (CFA) were carried out to determine the structural validity. Convergent validity was analysed by examining the relationships between OSS-TR with the Berg Balance Scale (BBS) and Trunk Impairment Scale (TIS). The test-retest reliability of the scale was assessed by intraclass correlation coefficient (ICC) and internal consistency was assessed by Cronbach’s alpha coefficient. The good fit determined according to the model fit criteria based on the CFA results confirmed the structural validity. Furthermore, the high associations between OSS-TR with the BBS (r = 0.766) and TIS (r = 0.720) supported convergent validity (p < 0.05). Test-retest reliability of the OSS-TR was excellent (ICC = 0.867). Moreover, internal consistency was high (Cronbach’s alpha = 0.948). The OSS-TR is a valid and reliable instrument for assessing sitting balance in Turkish-speaking PD patients. Regarding the results of the study, OSS-TR can be considered useful in the evaluation of sitting balance among PD patients in clinical and research settings.

An update on drug repurposing in Parkinson's disease: Preclinical and clinical considerations.

The strategy of drug repositioning has historically played a significant role in the identification of new treatments for Parkinson's disease. Still today, numerous clinical and preclinical studies are investigating drug classes, already marketed for the treatment of metabolic disorders, for their potential use in Parkinson's disease patients. While drug repurposing offers a promising, fast, and cost-effective path to new treatments, these drugs still require thorough preclinical evaluation to assess their efficacy, addressing the specific neurodegenerative mechanisms of the disease. This review explores the state-of-the-art approaches to drug repurposing for Parkinson's disease, highlighting particularly relevant aspects. Preclinical studies still predominantly rely on traditional neurotoxin-based animal models, which fail to effectively replicate disease progression and are characterized by significant variability in model severity and timing of drug treatment. Importantly, for almost all the drugs analyzed here, there is insufficient data regarding the mechanism of action responsible for the therapeutic effect. Regarding drug efficacy, these factors may obviously render results less reliable or comparable. Accordingly, future preclinical drug repurposing studies in the Parkinson's disease field should be carried out using next-generation animal models like α-synuclein-based models that, unfortunately, have to date been used mostly for studies of disease pathogenesis and only rarely in pharmacological studies.

Identifying potential genes driving ferroptosis in the substantia nigra and dopaminergic neurons in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder marked by dopaminergic (DA) neuron degeneration in the substantia nigra (SN). Conventional dopamine replacement therapies provide limited long-term efficacy and significant side effects. Emerging evidence suggests ferroptosis-a form of cell death driven by iron-dependent lipid peroxidation-contributes to PD pathology, though direct evidence linking dysregulation of ferroptosis-related genes in DA neuron loss in PD remains limited. This study explores the expression of ferroptosis-associated genes in the SN and DA neurons of PD patients, identifying potential therapeutic targets. We analyzed two independent RNA-seq datasets, GSE7621 and GSE8397 (GPL-96), from the GEO database to identify common differentially expressed ferroptosis-related genes in the SN of PD patients. We also conducted Gene Ontology and pathway enrichment analyses of these genes to explore the underlying mechanisms and constructed a protein-protein interaction network. The findings were further validated using an additional dataset, GSE49036. We further explored the dysregulation of these ferroptosis-related genes in DA neurons using RNA-seq data GSE169755, derived from DA neurons isolated from the SN of PD patients and controls. Lastly, the proposed hypothesis was experimentally validated in an in vitro PD model. This comprehensive multi-dataset analysis uncovers novel insights into the expression of ferroptosis-related genes in PD, suggesting potential biomarkers and therapeutic targets for mitigating DA neuron loss and PD progression.

The role of the somatosensory cortex in self-paced movement impairment in Parkinson's disease.

The aim of this work was to study the differences at the whole-brain level between self-paced and cued movement processing in Parkinson's disease (PD). High density electroencephalogram (HD-EEG) was recorded during the performance of self-paced movements (Bereitschaftspotential - BP) and visually cued movements (VMT) in PD patients (n=38) and in a group of healthy controls (HC, n=23). Oscillatory changes in the alpha, beta, and gamma frequencies were evaluated and correlated to the clinical scales- MDS-UPDRS and Freezing of Gait Questionnaire (FOGQ). The main difference in the alpha range was an activation in the basal ganglia area during VMT performance as compared to BP performance; this activation was present only in HC. The most important finding was observed in the high beta range: a higher activation of the right postcentral area during BP performance in PD subjects as compared to HC, correlating to the severity of FOG. Moreover, PD patients had lower gamma activation of the right frontal areas. A simplification of motor circuits and a hyperactivation of the right somatosensory cortex were observed in PD subjects. Future studies should be focused on this area to confirm or disprove its role in FOG.

Network topology and metabolic alterations in early- and mid-stage Parkinson's disease: insights from fluorodeoxyglucose PET imaging.

Parkinson's disease (PD) is a neurodegenerative disorder with distinct metabolic alterations in the brain, which are detectable via 18F-FDG PET. This study aims to delineate glucose metabolism patterns and network topology changes across early- and mid-stage PD patients. A total of 80 PD patients (Hoehn-Yahr stages 1-3) were retrospectively analyzed, including 40 early-stage and 40 mid-stage cases, along with 40 age-matched healthy controls. All participants underwent 18F-FDG PET imaging. The brain metabolic activity was quantified, and network topology was assessed using graph theory metrics. Statistical comparisons between PD stages and control groups were performed to identify significant differences in metabolic patterns and network alterations. Early-stage PD patients exhibited hypermetabolism in regions such as the pons and thalamus, with significant differences in metabolic activity compared with controls. Mid-stage PD patients showed more extensive hypermetabolism in the pons, right cerebellum, and putamen, alongside hypometabolism in the cuneus and calcarine regions. Hub node connectivity analysis revealed decreased connectivity in temporal and occipital lobes for both stages, while the limbic and frontal lobes showed enhanced connectivity. Compared with early-stage PD, mid-stage PD had reduced connectivity in the limbic system but increased in the frontal and occipital lobes. 18F-FDG PET imaging reveals progressive metabolic disruptions and network changes in PD, offering potential biomarkers for disease staging and therapeutic targeting, while also aiding in the understanding of disease progression and guiding therapeutic interventions.

Long-read sequencing revealed complex biallelic pentanucleotide repeat expansions in RFC1-related Parkinson’s disease

Biallelic intronic pentanucleotide repeat expansions, mainly (AAGGG)exp and/or (ACAGG)exp in RFC1, are detected in cerebellar ataxia, neuropathy and vestibular areflexia syndrome, late-onset ataxia, and in a wide disease spectrum including Charcot-Marie-Tooth disease, multiple system atrophy, and Parkinson’s disease (PD). However, the genotype-phenotype correlation and underlying mechanism are mostly unknown. We screened RFC1-repeat expansions in 1445 patients with parkinsonism. Comprehensive genetic and clinical, and pathological assessments were performed. We report two early-onset patients with PD carrying complex biallelic pentanucleotide repeat expansions in RFC1. Long-read sequencing revealed a novel repeat configuration of (AGGGG)exp(AAGGG)14 and a possible somatic variant of (AAGGG)exp(AATGG)exp(AAGGG)exp in the (AAGGG)exp alleles in two RFC1-related PD patients. RNA foci were detected in the (AGGGG)exp-expressed HEK293T cell line as well as (AAGGG)exp and (ACAGG)exp, supporting (AGGGG)exp as a novel pathogenic repeat motif. This work revealed complex genotypes with novel repeat configuration of (AGGGG)exp and possible somatic (AATGG)exp insertion in RFC1-related PD.

Adult Neurogenesis in the Subventricular Zone of Patients with Huntington's and Parkinson's Diseases and following Long-Term Treatment with Deep Brain Stimulation.

Parkinson's and Huntington's diseases are characterized by progressive neuronal loss. Previous studies using human postmortem tissues have shown the impact of neurodegenerative disorders on adult neurogenesis. The extent to which adult neural stem cells are activated in the subventricular zone and whether therapeutic treatments such as deep brain stimulation promote adult neurogenesis remains unclear. The goal of the present study is to assess adult neural stem cells activation and neurogenesis in the subventricular zone of patients with Huntington's and Parkinson's diseases who were treated or not by deep brain stimulation. Postmortem brain samples from Huntington's and Parkinson's disease patients who had received or not long-term deep brain stimulation of the subthalamic nucleus were used. Our results indicate a significant increase in the thickness of the subventricular zone and in the density of proliferating cells and activated stem cells in the brain of Huntington's disease subjects and Parkinson's disease patients treated with deep brain stimulation. We also observed an increase in the density of immature neurons in the brain of these patients. Overall, our data indicate that long-term deep brain stimulation of the subthalamic nucleus promotes cell proliferation and neurogenesis in the subventricular zone that are reduced in Parkinson's disease. Taken together, our results also provide a detailed characterization of the cellular composition of the adult human subventricular zone and caudate nucleus in normal condition and in Parkinson's and Huntington's diseases and demonstrate the plasticity of these regions in response to neurodegeneration. ANN NEUROL 2025.

Prevalence and associations of self-reported sleep problems in a large sample of patients with Parkinson's disease.

Sleep problems are important comorbid features of, and risk factors for, neurodegenerative diseases such as Parkinson's disease (PD). To assess the prevalence and associations of sleep problems in patients with PD we analysed data from almost 54,000 participants in the Fox Insight study, including data from 38,588 patients with PD. Sleep problems are common in PD, with ~84% of respondents with PD reporting difficulty falling or staying asleep. Experiences of insomnia, restless leg syndrome, vivid dreams, acting out dreams, and the use of sleep medication are over-represented in patients with PD compared with matched healthy controls. Male sex and PD onset before the age of 50 were also associated with a greater risk of sleep problems. A physician diagnosis of insomnia was associated with more symptoms of depression, impairment of cognition-dependent independence, and a lower quality of life. Sleep problems were also associated with a higher prevalence of OFF periods compared with PD patients without sleep problems. 6.7% of PD patients endorsed sleep complaints as their most bothersome symptom, and reported non-specific poor sleep quality as the most common sleep problem. These patients also had a better quality of life and lower depression and cognitive impairments than patients for whom postural instability was their most bothersome symptom, indicating the relative burden of sleep problems is contextualised by the severity of motor symptoms. Overall, these findings reinforce the high prevalence of sleep problems in a very large sample of PD patients, and indicate important associations of sleep problems with daily function and quality of life in PD.