Correlation between the MNCD classification-based staging of Parkinson's disease and quality of life: a cross-sectional study.

Parkinson's disease (PD) is a highly heterogeneous neurodegenerative disorder with varying clinical subtypes. Recently, a novel classification called MNCD (Motor/Non-motor/Cognition/Dependency) has been proposed, which can also include staging based on disease severity. We aim to investigate which staging, the MNCD classification and staging or Hoehn and Yahr (H&Y) staging, exhibits a stronger correlation with the 39-item Parkinson's Disease Questionnaire (PDQ-39). In a cross-sectional study conducted at our single center, 357 PD patients were recruited. Data encompassed scores from various assessments such as the Movement Disorder Society of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II, III and IV, Montreal Cognitive Assessment (MoCA), PDQ-39, and the H&Y scale. The mean age of these patients was 66.4 ± 9.1 years old, and the majority (54.6%) were male. MNCD stages: stage 1 (N = 3, 0.8%), stage 2 (N = 62, 17.4%), stage 3 (N = 187, 52.4%), stage 4 (N = 86, 24.1%), and stage 5 (N = 19, 5.3%). The top 5 most frequent PD-related clinical symptoms were sleep disturbances (89.6%), fatigue (69.7%), mild cognitive impairment (68.9%), constipation (65.8%), and postural instability (65.5%). The PDQ-39 demonstrated a positive correlation with both MNCD staging and H&Y staging. Moreover, the MNCD staging exhibited a stronger correlation with PDQ-39 compared to H&Y staging. The correlation between the MNCD classification and staging with the quality of life in PD patients is more statistically significant compared to the H&Y staging.

Grey matter alterations in restless legs syndrome: A coordinate-based meta-analysis.

Brain structural abnormalities in idiopathic restless legs syndrome have long been debated. Voxel-based morphometry is an objective structural magnetic resonance imaging technique to investigate regional grey matter volume or density differences between groups. In the last decade, voxel-based morphometry studies have exhibited inconsistent and conflicting findings regarding the presence and localization of brain grey matter alterations in restless legs syndrome. We therefore conducted a coordinate-based meta-analysis to quantitatively examine whether there were consistent grey matter findings in restless legs syndrome using the latest algorithms, seed-based d mapping with permutation of subject images. We included 12 voxel-based morphometry studies (13 datasets, 375 patients and 385 healthy controls). Our coordinate-based meta-analysis did not identify evidence of consistent grey matter alterations in restless legs syndrome. Grey matter alterations via voxel-based morphometry analysis are not therefore recommended to be used as a reliable surrogate neuroimaging marker for restless legs syndrome. This lack of consistency may be attributed to differences in sample size, genetics, gender distribution and age at onset, clinical heterogeneity (clinical course, anatomical distribution of symptoms, disease severity, disease duration, abnormal sensory profiles and comorbidity), and variations in imaging acquisition, data processing and statistical strategies. Longitudinal studies with multimodal neuroimaging techniques are needed to determine whether structural changes are dynamic and secondary to functional abnormalities.

[Application of diffusion tensor imaging in judging infarction time of acute ischemic cerebral infarction].

OBJECTIVE: To evaluate the clinical application value of diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) in judging infarction time phase of acute ischemic cerebral infarction. METHODS: To retrospective analysis DTI images of 52 patients with unilateral acute ischemic cerebral infarction (hyper-acute, acute and sub-acute) from the Affiliated Yancheng Hospital of Southeast University Medical College, which diagnosed by clinic and magnetic resonance imaging. Set the regions of interest (ROIs) of infarction lesions, brain tissue close to infarction lesions and corresponding contra (contralateral normal brain tissue) on DTI parameters mapping of fractional anisotropy (FA), volume ratio anisotropy (VRA), average diffusion coefficient (DCavg) and exponential attenuation (Exat), record the parameters values of ROIs and calculate the relative parameters value of infarction lesion to contra. Meanwhile, reconstruct the DTT images based on the seed points (infarction lesion and contra). The study compared each parameter value of infarction lesions, brain tissue close to infarction lesions and corresponding contra, also analysed the differences of relative parameters values in different infarction time phases. RESULTS: The DTT images of acute ischemic cerebral infarction in each time phase could show the manifestation of fasciculi damaged. The DCavg value of cerebral infarction lesions was lower and the Exat value was higher than contra in each infarction time phase (P<0.05). The FA and VRA value of cerebral infarction lesions were reduced than contra only in acute and sub-acute infarction (P<0.05). The FA, VRA and Exat value of brain tissue close to infarction lesions were increased and DCavg value was decreased than contra in hyper-acute infarction (P<0.05). There were no statistic differences of FA, VRA, DCavg and Exat value of brain tissue close to infarction lesions in acute and sub-acute infarction. The relative FA and VRA value of infarction lesion to contra gradually decreased from hyper-acute to sub-acute cerebral infarction (P<0.05), but there were no difference of the relative VRA value between acute and sub-acute cerebral infarction. The relative DCavg value of infarction lesion to contra in hyper-acute infarction than that in acute and sub-acute infarction (P<0.05), however there was also no difference between acute and sub-acute infarction. ROC curve showed the best diagnosis cut off value of relative FA, VRA and DCavg of infarction lesions to contra were 0.852, 0.886 and 0.541 between hyper-acute and acute cerebral infarction, the best diagnosis cut off value of relative FA was 0.595 between acute and sub-acute cerebral infarction, respectively. CONCLUSION: The FA, VRA, DCavg and Exat value have specific change mode in acute ischemic cerebral infarction of different infarction time phases, which can be combine used in judging infarction time phase of acute ischemic cerebral infarction without clear onset time, thus to help selecting the reasonable treatment protocols.

Comparison of the Efficacy and Safety Between Intravenous Thrombolysis, Direct Endovascular Therapy, and Bridging Therapy for Acute Basilar Artery Occlusion in Cerebral Infarction Patients.

OBJECTIVE: To compare the efficacy and safety of intravenous thrombolysis, direct endovascular therapy (EVT), and bridging therapy (BT = intravenous thrombolysis + EVT) for acute basilar artery occlusion cerebral infarction. METHODS: One hundred and fourteen patients with acute basilar artery occlusion cerebral infarctions admitted between January 2020 and August 2023 were selected. Differences in the reperfusion rate, prognosis, incidence of stroke-associated pneumonia, and mortality rate were compared among the 3 groups. RESULTS: There was no statistically significant difference in the percentage of patients who achieved successful reperfusion (86.8% vs. 84.2%) or complete reperfusion (72.1% vs. 68.4%) between the direct EVT and BT groups (both P > 0.05). There were no statistically significant differences in the rates of symptomatic intracranial hemorrhage (3.7% vs. 10.3% vs. 10.5%, P = 0.763). There were statistically significant differences in the rates of good prognosis (modified ranking scale score 0-2) (59.3% vs. 30.9% vs. 26.3%, P = 0.021), stroke-related pneumonia (29.6% vs. 66.2% vs. 36.8%, P = 0.002), and mortality (14.8% vs. 48.5% vs. 42.1%, P = 0.010) among the 3 treatment groups. According to the binary logistic regression analysis, a good prognosis was independently associated with a baseline National Institutes of Health Stroke Scale score ≤ 10 (odds ratio, 3.714; 95% confidence interval, 1.207-11.430; P = 0.022) and the incidence of stroke-associated pneumonia (odds ratio, 0.640; 95% confidence interval, 0.484-0.845; P = 0.002). CONCLUSIONS: Although there were differences in prognosis, mortality, and incidence of complications among the 3 treatment groups, after adjusting for confounding factors, prognosis was independently correlated only with the baseline NIHSS score and stroke-associated pneumonia but not with treatment methods.

Chronic smoking and brain gray matter changes: evidence from meta-analysis of voxel-based morphometry studies.

Structural neuroimaging studies on chronic smokers using voxel-based morphometry (VBM) had provided cumulative evidence of gray matter (GM) changes relative to nonsmokers. However, not all the studies reported entirely consistent findings. Here, we aimed at identifying consistent GM anomalies in chronic smokers by performing a meta-analysis, and a systematic search of VBM studies on chronic smokers and nonsmokers published in PubMed and Embase database from 2000 to April 2012. Meta-analysis was performed using a newly improved voxel-based meta-analytic tool, namely effect size signed differential mapping, to quantitatively explore the GM abnormalities between chronic smokers and nonsmokers. A total of 7 eligible VBM studies involving 213 chronic smokers and 205 nonsmokers met the inclusion criteria. A considerable regional GM volume decrease was detected in the anterior cingulate cortex (ACC) (BA 24) extending to BA32 in chronic smokers. The findings remain largely unchanged in the entire brain jackknife sensitivity analyses. The results of the present meta-analysis provide evidence of GM changes in ACC in chronic smokers which may be an important potential therapeutic neuro-target for nicotine dependence.

Association of polymorphism in rs2736990 of the α-synuclein gene with Parkinson's disease in a Chinese population.

BACKGROUND AND OBJECTIVE: Previous genetic studies in Parkinson's disease (PD) have provided conclusive evidence for association of genes with strong biological rationale for PD. Recently several studies in different populations have found a strong association between idiopathic PD and the single-nucleotide polymorphism (SNP) rs2736990, located within an intron of the α-synuclein (SNCA) gene. In this study, we aimed to verify these findings and to explore the characteristic of the association in a subset of Chinese Han PD patients. MATERIALS AND METHODS: A total of 515 unrelated patients with sporadic PD and 450 healthy ethnically matched control subjects were recruited consecutively for the study. Patients and healthy controls were genotyped for SNCA rs2736990 variant by polymerase chain reaction - ligase detection reaction. RESULTS: Our data showed a significant association between the rs2736990 polymorphism and PD, the frequency of the allele C in PD patients was significantly higher than that in controls (P = 0.017, OR = 1.26, 95% confident intervals (CI) =1.04-1.51). The distribution of C > T genotypes was different between patients and controls (P = 0.027). Furthermore, allele C of SNP rs2736990 in early-onset PD was significantly more frequent than that in healthy controls (P = 0.007, odds ratio = 1.60, 95% CI = 1.13-2.26). CONCLUSIONS: Our study demonstrated that SNCA rs2736990 C > T polymorphism was associated with susceptibility to PD in Chinese Han population. Further studies are needed to replicate the association we found.

Factors correlated with excessive daytime sleepiness in patients with Parkinson's disease: A polysomnography study.

OBJECTIVE: To explore the factors correlated with excessive daytime sleepiness (EDS) in patients with Parkinson's disease (PD). METHODS: A total of 239 PD patients were divided into two groups based on the presence of EDS (Epworth Sleepiness Scale score≥10) (PD-EDS vs. PD-non-EDS). Participants underwent an extensive assessment to determine demographic features, disease severity, polysomnography characteristics, and nonmotor symptoms. RESULTS: Of the 239 patients, 56 patients (23.4%) were classified as having PD combined with EDS. Binary logistic regression analysis showed that fatigue (Fatigue Severity Scale [FSS] score ≥4) (odds ratio [OR] [95% CI] = 4.897 [2.376-10.095], p < .001) and the respiratory-related microarousal index (OR [95% CI] = 2.063 [1.085-3.923], p = .027) were independent risk factors for EDS in PD patients. A priori-determined stratified analysis showed that after adjustment for confounding factors, the association of the respiratory-related microarousal index with EDS was significant (OR = 4.404, 95% CI 1.673-11.592, p trend = .036) in patients with respiratory arousal index scores in the highest quintile compared with those with scores in the lowest quintile. CONCLUSION: Our data revealed a close association among the respiratory-related microarousal index, FSS scores, and EDS. It can be speculated that fragmented sleep and pathological abnormalities of the central nervous system resulting in changes in arousal are major influencing factors of EDS in PD.

Effect of cerebral small vessel disease on cognitive impairment in Parkinson's disease.

OBJECTIVES: To explore the association between cerebral small vessel disease (cSVD) and cognitive impairment (CI) in Parkinson's disease (PD). METHODS: 81 PD patients were recruited into the study from September 2018 to December 2020. The demographic characteristics and radiologic and laboratory data were collected. Cognitive assessments were carried out using the Montreal Cognitive Assessment. The association between cSVD and cognitive impairment was analyzed using univariate and binary logistic regression analysis. RESULTS: The binary logistic regression analysis showed that, after correcting for age, educational years, hyperhomocysteinemia, hypertension, and diabetes mellitus, total cSVD scores (OR 1.55, 95% CI 1.07-2.27, P = 0.02), the presence of paraventricular white matter hyperintensity (PVH) (OR 11.78, 95% CI 3.08-45.01, P < 0.001), white matter hyperintensity (WMH) (OR 7.95, 95% CI 2.28-27.79, P = 0.001), and perivascular space (PVS) (OR 6.66, 95% CI 2.08-21.40, P = 0.001) were independent risk factors for PD-CI. CONCLUSION: The presence of cSVD was associated with cognitive dysfunction in patients with PD. It may be beneficial to manage cSVD to prevent the progression of cognitive impairment in patients with PD.

Correlation Between Intracranial Carotid Artery Calcification and Prognosis of Acute Ischemic Stroke After Intravenous Thrombolysis.

Objective: To investigate the correlation between prognosis and intracranial carotid artery calcification (ICAC) in patients with acute ischemic stroke (AIS) who receive intravenous thrombolysis (IVT). Methods: A total of 156 AIS patients who received IVT from March 2019 to March 2020 were enrolled. The modified Woodcock visual score was used to evaluate ICAC in nonenhanced head CT scans. Patients were divided into high calcification burden (HCB; score ≥3) and low calcification burden (LCB; score <3) groups. Demographic, laboratory, imaging and clinical data were compared between the two groups, and whether HCB was a prognostic factor was evaluated. Results: Compared with the LCB group, the HCB group had a higher incidence of atrial fibrillation (49.2 vs.22.1%, P < 0.001) and coronary heart disease (24.6 vs. 10.0%, P = 0.019) and higher serum homocysteine [15.31 (12.15, 17.50) vs. 14.40 (11.20, 16.20), P = 0.036] and hemoglobin A1c (6.93 ± 1.77 vs. 6.37 ± 0.74, P = 0.023) levels. Binary logistic regression analysis showed that atrial fibrillation (OR = 3.031, 95% CI: 1.312-7.006, P = 0.009) and HbA1c (OR = 1.488, 95% CI: 1.050-2.109, P = 0.026) were independent risk factors for ICAC. After adjusting for other risk factors, symptomatic-side and bilateral ICACs were independent risk factors for poor prognosis (OR = 1.969, 95% CI: 1.220-3.178, P = 0.006), (OR = 1.354, 95% CI: 1.065-1.722, P = 0.013) and mortality (OR = 4.245, 95% CI: 1.114-16.171, P = 0.034), (OR = 2.414, 95% CI = 1.152-5.060, P = 0.020) in patients with AIS who received IVT. Conclusion: ICAC is closely related to the prognosis of acute ischemic stroke after intravenous thrombolysis.

Association of cerebral microvascular perfusion and diffusion dynamics detected by intravoxel incoherent motion-diffusion weighted imaging with initial neurological function and clinical outcome in acute ischemic stroke.

BACKGROUND: This work aimed to explore the association of cerebral microvascular perfusion and diffusion dynamics measured by intravoxel incoherent motion (IVIM) imaging with initial neurological function and clinical outcome in acute stroke. METHODS: In total, 39 patients were assessed with admission National Institutes of Health Stroke Scale (NIHSS) and day-90 modified Rankin Scale (mRS). The parametrical maps of IVIM were obtained, including apparent diffusion coefficient (ADC), pseudo-diffusion coefficient (D*), true diffusion coefficient (D) and perfusion fraction (f). The fD* was the product of f and D*. Moreover, the ratios of lesioned/contralateral parameters (rADC, rD, rD*, rf and rfD*) were also obtained. The differences of these parameters between the poor outcome group and good outcome group were evaluated. Partial correlation analysis was used to evaluate the correlations between the admission NIHSS/day-90 mRS and each parameter ratio, with lesion volumes controlled. RESULTS: The ADC, D, D*, f and fD* values of lesions were significantly reduced than those of the contralateral regions. The rADC and rD were significantly decreased in the poor outcome group than good outcome group (all p < 0.01). With lesion volume controlled, rADC showed a weak negative correlation (r = -0.340, p = 0.037) and a notable negative correlation (r = -0.688, p < 0.001) with admission NIHSS score and day-90 mRS score, respectively. In addition, rD showed a strong negative correlation (r = -0.731, p < 0.001) with day-90 mRS score. CONCLUSION: Significant negative correlations were revealed between IVIM derived diffusion dynamics parameters and initial neurological function as well as clinical outcome for patients with acute ischemic stroke. IVIM can be therefore suggested as an effective non-invasive method for evaluating the acute ischemic stroke.

Blood neurofilament light chain in Parkinson disease and atypical parkinsonisms: A protocol for systematic review and meta-analysis.

BACKGROUND: Neurofilament light chain (NfL), an index of neuroaxonal injury, is a promising diagnostic and prognostic fluid biomarker with high translational value in many neurodegenerative disorders. Blood NfL measurement has been an exciting and active field of research in idiopathic Parkinson disease (PD) and atypical parkinsonisms. However, blood NfL levels in these parkinsonisms from existing literature were inconsistent. No comprehensive meta-analysis has ever been conducted. METHODS: Three major biomedical electronic databases PubMed, Embase, and Web of Science were comprehensively searched from inception to July 10, 2020. This protocol will be prepared based on the guidelines recommended by the statement of Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Original observational studies that measured blood (serum/plasma) NfL concentrations in patients with parkinsonisms (multiple system atrophy [MSA], progressive supranuclear palsy [PSP], corticobasal syndrome [CBS], and dementia with Lewy bodies [DLB]), and healthy controls (HCs) will be included. Quality assessment of the included studies will be performed using the Newcastle Ottawa Scale (NOS). Meta-analyses will be conducted using the STATA software version 13.0. The standardized mean differences as the measure of effect size and 95% confidence intervals were calculated for each comparison of blood NfL levels. Heterogeneity analysis, sensitivity analysis, publication bias, subgroup analysis, and meta-regression analysis will be carried out to test the robustness of the results. RESULTS: The meta-analysis will obtain the effect sizes of blood NfL levels in the following comparisons: PD versus HC, MSA versus HC, PSP versus HC, CBS versus HC, DLB versus HC, MSA versus PD, PSP versus PD, CBS versus PD, and DLB versus PD. CONCLUSIONS: The present meta-analysis will provide the quantitative evidence of NfL levels in idiopathic PD and atypical parkinsonisms, hoping to facilitate differential diagnoses in clinical practice. REGISTRATION NUMBER: INPLASY202070091.

Cerebrospinal fluid and blood levels of neurofilament light chain in Parkinson disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Parkinson disease (PD) is a common neurodegenerative disorder. Elevations of neurofilament light chain (NfL) concentrations in the cerebrospinal fluid (CSF) and blood are a marker of neuronal/axonal injury and degeneration. However, CSF and blood NfL alterations in patients with PD from existing studies remain inconclusive. To better understand these conflicting data, we will conduct a meta-analysis. METHODS: We will comprehensively search PubMed, Embase, and Web of Science databases from each database's inception to 7th June, 2020. This protocol will conform to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols. We will only include original studies published in English that evaluated differences of NfL concentrations in the CSF or blood between idiopathic PD patients and healthy controls. The Newcastle-Ottawa Scale will be used to evaluate the quality of the included studies. Meta-analyses will be carried out using the STATA software version 13.0. Between-group difference of NfL concentrations in the CSF and blood will be expressed as the weighted standardized mean difference. A random-effects model will be used. Supplementary analyses, such as heterogeneity analysis, sensitivity analysis, publication bias, subgroup analysis, and meta-regression analysis will be performed. RESULTS: The meta-analysis will provide the differences of NfL concentrations in the CSF and blood between patients with PD and healthy controls and will show the magnitudes of their effect sizes. CONCLUSIONS: This meta-analysis will provide the evidence of NfL concentrations in the CSF and blood in PD and we hope that our study has an important impact on clinical practice. REGISTRATION NUMBER: INPLASY202060025.

Predictors of Good Outcomes in Stroke Thrombolysis Guided by Tissue-Window.

BACKGROUND: Recently studies suggested that assessment of tissue-window can effectively guide thrombolysis in acute ischemic stroke patients with unknown time of onset or late presenting. This study aimed to evaluate predictors of good outcomes from thrombolysis in these patients. METHODS: Acute ischemic stroke patients received thrombolysis guided by computed tomography perfusion (CTP) from October 2018 to August 2019 were reviewed. Baseline characteristics and outcomes were collected. Good outcomes were defined as modified Rankin scale scores of 0 to 2 at 90 days. Logistic regression analysis was performed and the receiver operating characteristics analysis was used to determine cut-off values for the predictors of outcomes. RESULTS: Sixty-three patients were enrolled. The median age was 64 (interquartile range 57.75 to 72.5) years. The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 8 (interquartile range 3 to 13) and 41 (65.1%) patients had a good outcome at 90 days. Multivariate regression analysis showed smaller perfusion lesion (the sum of ischemic penumbra and infarcted core) (odds ratio: 0.961; 95% confidence interval, 0.931-0.992; P=0.013) and lower baseline NIHSS score (odds ratio: 0.759; 95% confidence interval, 0.644-0.895; P=0.001) were significant predictors for good outcomes. Receiver operating characteristics analysis was utilized to define optimal cut-off values for perfusion lesion [cut-off, 59 mL; area under curve (AUC), 0.761; sensitivity, 0.57; specificity, 0.93; P=0.001], ischemic penumbra (cut-off, 43.5 mL; AUC, 0.761; sensitivity, 0.62; specificity, 0.90; P=0.001), infarcted core (cut-off, 9.5 mL; AUC, 0.665; sensitivity, 0.43; specificity, 0.93; P=0.035), and baseline NIHSS score (cut-off, 8.5; AUC, 0.880; sensitivity, 0.81; specificity, 0.88; P<0.001). CONCLUSIONS: This study suggested that smaller perfusion lesion and lower baseline NIHSS score may be helpful to predict favorable prognosis of stroke patients who receive thrombolysis guided by tissue-window.

Gray matter alterations in restless legs syndrome: A coordinate-based meta-analysis.

BACKGROUND: Voxel-based morphometry (VBM) is an objective structural magnetic resonance imaging (MRI) technique which allows researchers to investigate group-level differences in regional gray matter (GM) volume or density over the whole brain. In the last decade, VBM studies in restless leg syndrome (RLS) have exhibited inconsistent and conflicting findings. METHODS: Studies will be identified through a computerized literature search of the following databases: PubMed, Web of Science, and Embase until October 1, 2018 and updated on March 1, 2020. This protocol will be performed in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P). In addition, we will follow the recent guidelines and recommendations for coordinate-based meta-analysis (CBMA). This CBMA will be performed with the seed-based d mapping with permutation of subject images (SDM-PSI) software. RESULTS: This CBMA will offer the latest evidence of GM alterations in RLS. CONCLUSIONS: To our knowledge, this will be the first CBMA that pooled VBM findings in RLS. This quantitative evidence of GM alterations will characterize brain morphometry of RLS. PROSPERO REGISTRATION NUMBER: CRD42018117014.

Endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion (BEST): an open-label, randomised controlled trial.

BACKGROUND: Previous randomised trials have shown an overwhelming benefit of mechanical thrombectomy for treating patients with stroke caused by large vessel occlusion of the anterior circulation. Whether endovascular treatment is beneficial for vertebrobasilar artery occlusion remains unknown. In this study, we aimed to investigate the safety and efficacy of endovascular treatment of acute strokes due to vertebrobasilar artery occlusion. METHODS: We did a multicentre, randomised, open-label trial, with blinded outcome assessment of thrombectomy in patients presenting within 8 h of vertebrobasilar occlusion at 28 centres in China. Patients were randomly assigned (1:1) to endovascular therapy plus standard medical therapy (intervention group) or standard medical therapy alone (control group). The randomisation sequence was computer-generated and stratified by participating centres. Allocation concealment was implemented by use of sealed envelopes. The primary outcome was a modified Rankin scale (mRS) score of 3 or lower (indicating ability to walk unassisted) at 90 days, assessed on an intention-to-treat basis. The primary safety outcome was mortality at 90 days. Secondary safety endpoints included the rates of symptomatic intracranial haemorrhage, device-related complications, and other severe adverse events. The BEST trial is registered with ClinicalTrials.gov, NCT02441556. FINDINGS: Between April 27, 2015, and Sept 27, 2017, we assessed 288 patients for eligibility. The trial was terminated early after 131 patients had been randomly assigned (66 patients to the intervention group and 65 to the control group) because of high crossover rate and poor recruitment. In the intention-to-treat analysis, there was no evidence of a difference in the proportion of participants with mRS 0-3 at 90 days according to treatment (28 [42%] of 66 patients in the intervention group vs 21 [32%] of 65 in the control group; adjusted odds ratio [OR] 1·74, 95% CI 0·81-3·74). Secondary prespecified analyses of the primary outcome, done to assess the effect of crossovers, showed higher rates of mRS 0-3 at 90 days in patients who actually received the intervention compared with those who received standard medical therapy alone in both per-protocol (28 [44%] of 63 patients with intervention vs 13 [25%] of 51 with standard therapy; adjusted OR 2·90, 95% CI 1·20-7·03) and as-treated (36 [47%] of 77 patients with intervention vs 13 [24%] of 54 with standard therapy; 3·02, 1·31-7·00) populations. The 90-day mortality was similar between groups (22 [33%] of 66 patients in the intervention vs 25 [38%] of 65 in the control group; p=0·54) despite a numerically higher prevalence of symptomatic intracranial haemorrhage in the intervention group. INTERPRETATION: There was no evidence of a difference in favourable outcomes of patients receiving endovascular therapy compared with those receiving standard medical therapy alone. Results might have been confounded by loss of equipoise over the course of the trial, resulting in poor adherence to the assigned study treatment and a reduced sample size due to the early termination of the study. FUNDING: Jiangsu Provincial Special Program of Medical Science.

Regional gray matter reductions associated with mild cognitive impairment in Parkinson's disease: A meta-analysis of voxel-based morphometry studies.

Mild cognitive impairment (MCI) is inconclusively associated with regional gray matter (GM) abnormalities in Parkinson's disease (PD). We aimed to quantitatively evaluate whole-brain voxel-based morphometry (VBM) studies that have investigated brain GM changes in PD patients with MCI (PD-MCI). Seed-based d Mapping, a well-validated coordinate-based meta-analytic approach, was utilized. We included 20 VBM studies that reported 22 datasets containing 504 patients with PD-MCI and 554 PD patients without MCI (PD-NCI). The most reliable finding identified in this meta-analysis was that patients with PD-MCI exhibited greater GM atrophy in the left anterior insula than those with PD-NCI. Our findings further suggest that several moderators (age, gender, educational level, disease stage, severity of motor disability, and the severity of cognitive impairments) in PD-MCI individuals, as well as scanner field-strength, may drive heterogeneous GM changes across studies. GM abnormalities in the anterior insula, an important cognitive hub involved in switching between neural networks, contribute to understanding the neural substrates of MCI in PD, which may serve as a biomarker of PD-MCI.

Risk Factors for Mild Cognitive Impairment in Patients with Aneurysmal Subarachnoid Hemorrhage Treated with Endovascular Coiling.

OBJECTIVE: To assess the potential early risk factors of mild cognitive impairment after aneurysmal subarachnoid hemorrhage. METHODS: We prospectively enrolled patients with aneurysmal subarachnoid hemorrhage treated with endovascular coiling during a 5-year period. The demographic characteristics and radiologic and laboratory data were collected. Cognitive assessments were carried out using the Montreal Cognitive Assessment at 6 months after ictus. Multivariate logistic regression was used to determine the risk factors associated with the development of mild cognitive impairment. RESULTS: Of 152 patients, 59 patients (39%) developed cognitive impairment 6 months later. Univariate analysis showed that the patients with anterior communicating artery or anterior cerebral artery aneurysms (P < 0.001) with Glasgow Outcome Scale score of 7 or less at ictus (P = 0.002), Hunt and Hess grade of 3 or higher (P = 0.002), and Fisher grade of 3 or higher (P = 0.032) were more likely to develop mild cognitive impairment. The risk of mild cognitive impairment was increased for patients who had delayed cerebral ischemia (P = 0.040) and hydrocephalus (P = 0.002). In multivariate logistic regression analysis, mild cognitive impairment was independently associated with anterior communicating artery or anterior cerebral aneurysms (odds ratio [OR], 11.046; 95% confidence interval [CI], 3.371-36.198; P < 0.001), delayed cerebral ischemia (OR, 6.153; 95% CI, 1.587-23.855; P = 0.009), and hydrocephalus (OR, 8.768; 95% CI, 2.115-36.345; P = 0.003). CONCLUSIONS: The location of the aneurysm, delayed cerebral ischemia, and hydrocephalus were independently associated with the occurrence of mild cognitive impairment after aneurysmal subarachnoid hemorrhage and can contribute to improved identification of patients at high risk for mild cognitive impairment.

Gray Matter Abnormalities Associated With Chronic Back Pain: A Meta-Analysis of Voxel-based Morphometric Studies.

BACKGROUND: Studies employing voxel-based morphometry have reported inconsistent findings on the association of gray matter (GM) abnormalities with chronic back pain (CBP). We, therefore, performed a meta-analysis of available studies to identify the most consistent GM regions associated with CBP. METHODS: The PubMed, Embase, and Web of Science databases were searched from January 2000 to May 29, 2016. Comprehensive meta-analyses of whole-brain voxel-based morphometry studies to identify the most robust GM abnormalities in CBP were conducted using the Seed-based d Mapping software package. RESULTS: A total of 10 studies, comprising 293 patients with CBP and 624 healthy controls, were included in the meta-analyses. The most robust findings of regional GM decreases in patients with CBP compared with healthy controls were identified in the bilateral medial prefrontal cortex extending to the anterior cingulate cortex, the right medial prefrontal cortex extending to the orbitofrontal cortex. Regional GM decreases in the left anterior insula were less robustly observed. CONCLUSIONS: The present study demonstrates a pattern of GM alterations in CBP. These data further advance our understanding of the pathophysiology of CBP.

Aberrant spontaneous low-frequency brain activity in amnestic mild cognitive impairment: A meta-analysis of resting-state fMRI studies.

Recent resting-state functional magnetic resonance imaging (rs-fMRI) studies have provided strong evidence of abnormal spontaneous brain activity in amnestic mild cognitive impairment (aMCI). However, the conclusions have been inconsistent. A meta-analysis of whole-brain rs-fMRI studies that measured differences in the amplitude of low-frequency fluctuations (ALFF) between aMCI patients and healthy controls was conducted using the Seed-based d Mapping software package. Twelve studies reporting 14 datasets were included in the meta-analysis. Compared to healthy controls, patients with aMCI showed decreased ALFFs in the bilateral precuneus/posterior cingulate cortices, bilateral frontoinsular cortices, left occipitotemporal cortex, and right supramarginal gyrus and increased ALFFs in the right lingual gyrus, left middle occipital gyrus, left hippocampus, and left inferior temporal gyrus. A meta-regression analysis demonstrated that the increased severity of cognitive impairment in aMCI patients was associated with greater decreases in ALFFs in the cuneus/precuneus cortices. Our comprehensive meta-analysis suggests that aMCI is associated with widespread aberrant regional spontaneous brain activity, predominantly involving the default mode, salience, and visual networks, which contributes to understanding its pathophysiology.

Gray matter abnormalities associated with fibromyalgia: A meta-analysis of voxel-based morphometric studies.

OBJECTIVES: Studies employing voxel-based morphometry (VBM) have reported inconsistent findings on the association of gray matter (GM) abnormalities with fibromyalgia. The aim of the present study is to identify the most prominent and replicable GM areas that involved in fibromyalgia. METHODS: A systematic search of the PubMed database from January 2000 to September 2015 was performed to identify eligible whole-brain VBM studies. Comprehensive meta-analyses to investigate regional GM abnormalities in fibromyalgia were conducted with the Seed-based d Mapping software package. RESULTS: Seven studies, reporting nine comparisons and including a grand total of 180 fibromyalgia patients and 126 healthy controls, were included in the meta-analyses. In fibromyalgia patients compared with healthy controls, regional GM decreases were consistently found in the bilateral anterior cingulate/paracingulate cortex/medial prefrontal cortex, the bilateral posterior cingulate/paracingulate cortex, the left parahippocampal gyrus/fusiform cortex, and the right parahippocampal gyrus/hippocampus. Regional GM increases were consistently found in the left cerebellum. Meta-regression demonstrated that age was correlated with GM anomalies in fibromyalgia patients. CONCLUSIONS: The current meta-analysis identified a characteristic pattern of GM alterations within the medial pain system, default mode network, and cerebro-cerebellar circuits, which further supports the concept that fibromyalgia is a symptom complex involving brain areas beyond those implicated in chronic pain.