Background and purpose The pathophysiology of Parkinson’s disease (PD) remains unclear. Voxel‐based morphometry (VBM) detects local structural differences in brain tissue such as grey matter volume (GMV) between groups, which is helpful in understanding the pathophysiology of PD. Published VBM studies of GMV changes in PD have shown inconsistent results. Therefore, a voxel‐wise meta‐analysis of VBM studies was conducted to detect consistent GMV changes in PD. Methods The published literature was searched comparing whole‐brain GMV between PD patients and healthy controls (HCs) using VBM. Coordinates were extracted for the clusters of significant GMV differences between PD patients and HCs. The meta‐analysis was performed by seed‐based d mapping software. Results A total of 63 studies with 2867 PD patients and 1990 HCs were included. Significant GMV reductions in some brain regions were detected in PD patients, which were involved in the basal ganglia, theory of mind, vocal and visual networks. These findings remained largely unchanged in the jackknife sensitivity analysis, and no significant heterogeneity or publication bias was detected. Conclusions Parkinson’s disease patients have GMV reductions in a number of brain regions involved in specific networks. These findings provide morphological evidence for the pathophysiology of PD.

Purpose: This study aimed to identify consistent gray matter volume (GMV) changes in the two subtypes of multiple system atrophy (MSA), including parkinsonism subtype (MSA-P), and cerebellar subtype (MSA-C), by conducting a voxel-wise meta-analysis of whole brain voxel-based morphometry (VBM) studies.Method: VBM studies comparing MSA-P or MSA-C and healthy controls (HCs) were systematically searched in the PubMed, Embase, and Web of Science published from 1974 to 20 October 2020. A quantitative meta-analysis of VBM studies on MSA-P or MSA-C was performed using the effect size-based signed differential mapping (ES-SDM) method separately. A complementary analysis was conducted using the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) method, which allows a familywise error rate (FWE) correction for multiple comparisons of the results, for further validation of the results.Results: Ten studies were included in the meta-analysis of MSA-P subtype, comprising 136 MSA-P patients and 211 HCs. Five studies were included in the meta-analysis of MSA-C subtype, comprising 89 MSA-C patients and 134 HCs. Cerebellum atrophy was detected in both MSA-P and MSA-C, whereas basal ganglia atrophy was only detected in MSA-P. Cerebral cortex atrophy was detected in both subtypes, with predominant impairment of the superior temporal gyrus, inferior frontal gyrus, temporal pole, insula, and amygdala in MSA-P and predominant impairment of the superior temporal gyrus, middle temporal gyrus, fusiform gyrus, and lingual gyrus in MSA-C. Most of these results survived the FWE correction in the complementary analysis, except for the bilateral amygdala and the left caudate nucleus in MSA-P, and the right superior temporal gyrus and the right middle temporal gyrus in MSA-C. These findings remained robust in the jackknife sensitivity analysis, and no significant heterogeneity was detected.Conclusion: A different pattern of brain atrophy between MSA-P and MSA-C detected in the current study was in line with clinical manifestations and provided the evidence of the pathophysiology of the two subtypes of MSA.

BackgroundA large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers.MethodsA total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed.Findings155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition.ConclusionsOur data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

Background: The causal relationship between serum lipid levels and the risk of Parkinson's disease (PD) remains largely uncertain. We summarized the existing controversial evidence on this topic. Methods: We searched the electronic databases for observational studies from January 1988 to March 2020. We applied random-effects models to calculate pooled relative risk (RR) with their 95% confidence intervals (CI). Random-effects dose-response meta-analyses were further conducted to explore the dose-risk relationship. Results: Twelve cohort studies and three case-control studies were included in this meta-analysis. Higher levels of serum low-density lipoprotein cholesterol (LDL-C) were inversely associated with the subsequent risk of PD (RR 0.73, 95% CI 0.57–0.93), whereas, there were no associations between serum levels of total cholesterol (TC) (RR 0.91, 95% CI 0.73–1.13), high-density lipoprotein cholesterol (HDL-C) (RR 0.97, 95% CI 0.73–1.27), or triglycerides (TG) (RR 0.85, 95% CI 0.55–1.29) and the risk of PD. Further dose-response meta-analysis revealed that every 38.6 mg/dL (1mmol/L) increase in serum LDL-C correlates with a 7% decreased risk of PD. Conclusions: Our paper supports the protective effect of higher serum LDL-C on the subsequent risk of PD. More prospective cohort studies are warranted to confirm the conclusion, and further fundamental researches are needed to elucidate the underlying biological mechanisms.

Background: Sleep disorders are common but under-researched symptoms in patients with multiple system atrophy (MSA). We investigated the frequency and factors associated with sleep-related symptoms in patients with MSA and the impact of sleep disturbances on disease severity. Methods: This cross-sectional study involved 165 patients with MSA. Three sleep-related symptoms, namely Parkinson's disease (PD)-related sleep problems (PD-SP), excessive daytime sleepiness (EDS), and rapid eye movement sleep behavior disorder (RBD), were evaluated using the PD Sleep Scale-2 (PDSS-2), Epworth Sleepiness Scale (ESS), and RBD Screening Questionnaire (RBDSQ), respectively. Disease severity was evaluated using the Unified MSA Rating Scale (UMSARS). Results: The frequency of PD-SP (PDSS-2 score of ≥18), EDS (ESS score of ≥10), and RBD (RBDSQ score of ≥5) in patients with MSA was 18.8%, 27.3%, and 49.7%, respectively. The frequency of coexistence of all three sleep-related symptoms was 7.3%. Compared with the cerebellar subtype of MSA (MSA-C), the parkinsonism subtype of MSA (MSA-P) was associated with a higher frequency of PD-SP and EDS, but not of RBD. Binary logistic regression revealed that the MSA-P subtype, a higher total UMSARS score, and anxiety were associated with PD-SP; that male sex, a higher total UMSARS score, the MSA-P subtype, and fatigue were associated with EDS; and that male sex, a higher total UMSARS score, and autonomic onset were associated with RBD in patients with MSA. Stepwise linear regression showed that the number of sleep-related symptoms (PD-SP, EDS, and RBD), disease duration, depression, fatigue, and total Montreal Cognitive Assessment score were predictors of disease severity in patients with MSA. Conclusions: Sleep-related disorders were associated with both MSA subtypes and the severity of disease in patients with MSA, indicating that sleep disorders may reflect the distribution and degree of dopaminergic/non-dopaminergic neuron degeneration in MSA.

Background Abnormal eye movements are common in spinocerebellar ataxias Type 3 (SCA3). We conducted the research to explore the frequency of abnormal eye movements in Chinese patients with SCA3, to compare the demographic and clinical characteristics between SCA3 patients with and without each type of abnormal eye movement, and to explore the correlation between abnormal eye movements and the severity of ataxia. Methods Seventy-four patients with SCA3 were enrolled in this cross-sectional study. Six types of abnormal eye movements including impaired smooth pursuit, increased square-wave jerks (SWJ), gaze-evoked nystagmus (GEN), slowing of saccades, saccadic hypo/hypermetria and supranuclear gaze palsy were evaluated by experienced neurologists. The severity of ataxia was evaluated by Scale for the Assessment and Rating of Ataxia (SARA). Results The prevalence of impaired smooth pursuit, increased SWJ, GEN, slowing of saccades, saccadic hypo/hypermetria and supranuclear gaze palsy in Chinese SCA3 patients was 28.4, 13.5, 78.4, 41.9, 23.0, and 5.4%, respectively. SCA3 patients with GEN had higher scores of International Cooperative Ataxia Rating Scale (ICARS-IV) and total ICARS, and longer length of CAG repeat than patients without GEN. SCA3 patients with slowing of saccades had a longer disease duration, higher scores of ICARS-I, ICARS-II, total ICARS and SARA than patients without slowing of saccades. SCA3 patients with saccadic hypo/hypermetria had higher scores of ICARS-III, ICARS-IV, and SARA than patients without saccadic hypo/hypermetria. The demographic and clinical characteristics did not differ significantly between SCA3 patients with and without impaired smooth pursuit, increased SWJ, or supranuclear gaze palsy. Multivariate linear regression showed that the number of abnormal eye movements (0–6), disease duration, Hamilton Depression Rating Scale-24 (HDRS-24) score, and CAG repeat length were positively correlated with SARA score, whereas Montreal Cognitive Assessment (MoCA) score was negatively correlated with SARA score in SCA3. Conclusions An increased number of abnormal eye movement types correlated with the severity of ataxia in SCA3.

Background: While a cochlear implant (CI) can restore access to audibility in deaf children, implanted children may still have difficulty in concentrating. Previous studies have revealed a close relationship between sensory gating and attention. However, whether CI children have deficient auditory sensory gating remains unclear.Methods: To address this issue, we measured the event-related potentials (ERPs), including P50, N100, and P200, evoked by paired tone bursts (S1 and S2) in CI children and normal-hearing (NH) controls. Suppressed amplitudes for S2 compared with S1 in these three ERPs reflected sensory gating during early and later phases, respectively. A Swanson, Nolan, and Pelham IV (SNAP-IV) scale was performed to assess the attentional performance.Results: Significant amplitude differences between S1 and S2 in N100 and P200 were observed in both NH and CI children, indicating the presence of sensory gating in the two groups. However, the P50 suppression was only found in NH children and not in CI children. Furthermore, the duration of deafness was significantly positively correlated with the score of inattention in CI children.Conclusion: Auditory sensory gating can develop but is deficient during the early phase in CI children. Long-term auditory deprivation has a negative effect on sensory gating and attentional performance.

No abstract