6 research outputs found
Preoperative REM Sleep Behavior Disorder and Subthalamic Nucleus Deep Brain Stimulation Outcome in Parkinson Disease 1 Year After Surgery
International audienceBackground and Objectives To determine whether patients with Parkinson disease (PD) eligible for subthalamic nucleus deep brain stimulation (STN-DBS) with probable REM sleep behavior disorder (RBD) preoperatively could be more at risk of poorer motor, nonmotor, and quality of life outcomes 12 months after surgery compared to those without RBD.Methods We analyzed the preoperative clinical profile of 448 patients with PD from a French multicentric prospective study (PREDISTIM) according to the presence or absence of probable RBD based on the RBD Single Question and RBD Screening Questionnaire. Among the 215 patients with PD with 12 months of follow-up after STN-DBS, we compared motor, cognitive, psycho-behavioral profile, and quality of life outcomes in patients with (pre-opRBD+) or without (pre-opRBDâ) probable RBD preoperatively.Results At preoperative evaluation, pre-opRBD+ patients were older (61 ± 7.2 vs 59.5 ± 7.7 years; p = 0.02), had less motor impairment (Movement Disorder Societyâsponsored version of the Unified Parkinsonâs Disease Rating Scale [MDS-UPDRS] III âoffâ: 38.7 ± 16.2 vs 43.4 ± 7.1; p = 0.03) but more nonmotor symptoms on daily living activities (MDS-UPDRS I: 12.6 ± 5.5 vs 10.7 ± 5.3; p < 0.001), had more psychobehavioral manifestations (Ardouin Scale of Behavior in Parkinson's Disease total: 7.7 ± 5.1 vs 5.1 ± 0.4; p = 0.003), and had worse quality of life (Parkinson's Disease Questionnaireâ39: 33 ± 12 vs 29 ± 12; p = 0.03), as compared to pre-opRBDâ patients. Both pre-opRBD+ and pre-opRBDâ patients had significant MDS-UPDRS IV score decrease (â37% and â33%, respectively), MDS-UPDRS III âmed âoffâ/stim âonââ score decrease (â52% and â54%), and dopaminergic treatment decrease (â52% and â49%) after surgery, with no between-group difference. There was no between-group difference for cognitive and global quality of life outcomes.Conclusions In patients with PD eligible for STN-DBS, the presence of probable RBD preoperatively is not associated with a different clinical outcome 1 year after neurosurgery. Trial Registration Information NCT02360683.Classification of Evidence This study provides Class II evidence that in patients with PD eligible for STN-DBS, the presence of probable RBD preoperatively is not associated with poorer outcomes 1 year post surgery
Unravelling the etiology of sporadic late-onset cerebellar ataxia in a cohort of 205 patients: a prospective study
BACKGROUND: Despite recent progress in the field of genetics, sporadic late-onset (>â40Â years) cerebellar ataxia (SLOCA) etiology remains frequently elusive, while the optimal diagnostic workup still needs to be determined. We aimed to comprehensively describe the causes of SLOCA and to discuss the relevance of the investigations. METHODS: We included 205 consecutive patients with SLOCA seen in our referral center. Patients were prospectively investigated using exhaustive clinical assessment, biochemical, genetic, electrophysiological, and imaging explorations. RESULTS: We established a diagnosis in 135 (66%) patients and reported 26 different causes for SLOCA, the most frequent being multiple system atrophy cerebellar type (MSA-C) (41%). Fifty-one patients (25%) had various causes of SLOCA including immune-mediated diseases such as multiple sclerosis or anti-GAD antibody-mediated ataxia; and other causes, such as alcoholic cerebellar degeneration, superficial siderosis, or Creutzfeldt-Jakob disease. We also identified 11 genetic causes in 20 patients, including SPG7 (nâ=â4), RFC1-associated CANVAS (nâ=â3), SLC20A2 (nâ=â3), very-late-onset Friedreich's ataxia (nâ=â2), FXTAS (nâ=â2), SCA3 (nâ=â1), SCA17 (nâ=â1), DRPLA (nâ=â1), MYORG (nâ=â1), MELAS (nâ=â1), and a mitochondriopathy (nâ=â1) that were less severe than MSA-C (pâ<â0.001). Remaining patients (34%) had idiopathic late-onset cerebellar ataxia which was less severe than MSA-C (pâ<â0.01). CONCLUSION: Our prospective study provides an exhaustive picture of the etiology of SLOCA and clues regarding yield of investigations and diagnostic workup. Based on our observations, we established a diagnostic algorithm for SLOCA
Mini-Exome Coupled to Read-Depth Based Copy Number Variation Analysis in Patients with Inherited Ataxias
International audienceNext-generation sequencing (NGS) has an established diagnostic value for inherited ataxia. However, the need of a rigorous process of analysis and validation remains challenging. Moreover, copy number variations (CNV) or dynamic expansions of repeated sequence are classically considered not adequately detected by exome sequencing technique. We applied a strategy of mini-exome coupled to read-depth based CNV analysis to a series of 33 patients with probable inherited ataxia and onset <50 years. The mini-exome consisted of the capture of 4,813 genes having associated clinical phenotypes. Pathogenic variants were found in 42% and variants of uncertain significance in 24% of the patients. These results are comparable to those from whole exome sequencing and better than previous targeted NGS studies. CNV and dynamic expansions of repeated CAG sequence were identified in three patients. We identified both atypical presentation of known ataxia genes (ATM, NPC1) and mutations in genes very rarely associated with ataxia (ERCC4, HSD17B4). We show that mini-exome bioinformatics data analysis allows the identification of CNV and dynamic expansions of repeated sequence. Our study confirms the diagnostic value of the proposed genetic analysis strategy. We also provide an algorithm for the multidisciplinary process of analysis, interpretation, and validation of NGS data