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Developmental neuroplasticity of the white matter connectome in children with perinatal stroke

期刊: NEUROLOGY, 2020; 95 (18)

Objective To employ diffusion imaging connectome methods to explore network development in the contralesional hemisphere of children with perinatal stroke and its relationship to clinical function. We hypothesized alterations in global efficiency of the intact hemisphere would correlate with clinical disability. Methods Children with unilateral perinatal arterial (n = 26) or venous (n = 27) stroke and typically developing controls (n = 32) underwent 3T diffusion and T1 anatomical MRI and completed established motor assessments. A validated atlas coregistered to whole-brain tractography for each individual was used to estimate connectivity between 47 regions. Graph theory metrics (assortativity, hierarchical coefficient of regression, global and local efficiency, and small worldness) were calculated for the left hemisphere of controls and the intact contralesioned hemisphere of both stroke groups. Validated clinical motor assessments were then correlated with connectivity outcomes. Results Global efficiency was higher in arterial strokes compared to venous strokes (p < 0.001) and controls (p < 0.001) and was inversely associated with all motor assessments (all p < 0.012). Additional graph theory metrics including assortativity, hierarchical coefficient of regression, and local efficiency also demonstrated consistent differences in the intact hemisphere associated with clinical function. Conclusions The structural connectome of the contralesional hemisphere is altered after perinatal stroke and correlates with clinical function. Connectomics represents a powerful tool to understand whole brain developmental plasticity in children with disease-specific cerebral palsy.

Global prevalence and burden of HIV-associated neurocognitive disorder A meta-analysis

期刊: NEUROLOGY, 2020; 95 (19)

Objective To characterize the prevalence and burden of HIV-associated neurocognitive disorder (HAND) and assess associated factors in the global population with HIV. Methods We searched PubMed and Embase for cross-sectional or cohort studies reporting the prevalence of HAND or its subtypes in HIV-infected adult populations from January 1, 1996, to May 15, 2020, without language restrictions. Two reviewers independently undertook the study selection, data extraction, and quality assessment. We estimated pooled prevalence of HAND by a random effects model and evaluated its overall burden worldwide. Results Of 5,588 records identified, we included 123 studies involving 35,513 participants from 32 countries. The overall prevalence of HAND was 42.6% (95% confidence interval [CI] 39.7-45.5) and did not differ with respect to diagnostic criteria used. The prevalence of asymptomatic neurocognitive impairment, mild neurocognitive disorder, and HIV-associated dementia were 23.5% (20.3-26.8), 13.3% (10.6-16.3), and 5.0% (3.5-6.8) according to the Frascati criteria, respectively. The prevalence of HAND was significantly associated with the level of CD4 nadir, with a prevalence of HAND higher in low CD4 nadir groups (mean/median CD4 nadir <200 45.2% [40.5-49.9]) vs the high CD4 nadir group (mean/median CD4 nadir >= 200 37.1% [32.7-41.7]). Worldwide, we estimated that there were roughly 16,145,400 (95% CI 15,046,300-17,244,500) cases of HAND in HIV-infected adults, with 72% in sub-Saharan Africa (11,571,200 cases, 95% CI 9,600,000-13,568,000). Conclusions Our findings suggest that people living with HIV have a high burden of HAND in the anti-retroviral therapy (ART) era, especially in sub-Saharan Africa and Latin America. Earlier initiation of ART and sustained adherence to maintain a high-level CD4 cell count and prevent severe immunosuppression is likely to reduce the prevalence and severity of HAND.

Sleep duration, midday napping, and sleep quality and incident stroke The Dongfeng-Tongji cohort

期刊: NEUROLOGY, 2020; 94 (4)

Objective To investigate the associations of sleep duration, midday napping, sleep quality, and change in sleep duration with risk of incident stroke and stroke subtypes. Methods Among 31,750 participants aged 61.7 years on average at baseline from the Dongfeng-Tongji cohort, we used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident stroke. Results Compared with sleeping 7 to <8 hours/night, those reporting longer sleep duration (>= 9 hours/night) had a greater risk of total stroke (hazard ratio [HR] 1.23; 95% confidence interval [CI] 1.07-1.41), while shorter sleep (<6 hours/night) had no significant effect on stroke risk. The HR (95% CI) of total stroke was 1.25 (1.03-1.53) for midday napping >90 minutes vs 1-30 minutes. The results were similar for ischemic stroke. Compared with good sleep quality, those with poor sleep quality showed a 29%, 28%, and 56% higher risk of total, ischemic, and hemorrhagic stroke, respectively. Moreover, we observed significant joint effects of sleeping >= 9 hours/night and midday napping >90 minutes (HR 1.85; 95% CI 1.28-2.66), and sleeping >= 9 hours/night and poor sleep quality (HR 1.82; 95% CI 1.33-2.48) on risk of total stroke. Furthermore, compared with persistently sleeping 7-9 hours/night, those who persistently slept >= 9 hours/night or switched from 7 to 9 hours to >= 9 hours/night had a higher risk of total stroke. Conclusions Long sleep duration, long midday napping, and poor sleep quality were independently and jointly associated with higher risks of incident stroke. Persistently long sleep duration or switch from average to long sleep duration increased the risk of stroke.

Renal impairment on clinical outcomes following endovascular recanalization

期刊: NEUROLOGY, 2020; 94 (5)

ObjectiveTo determine the influence of renal impairment (RI) on clinical outcomes at 3 months and the risk of recurrent stroke in patients presenting with emergent large vessel occlusion (ELVO) treated with emergent endovascular treatment (EVT).MethodsConsecutive patients with anterior circulation stroke due to ELVO treated with EVT in 21 endovascular centers were included. Multivariate regressions were used to evaluate the association of RI with mortality, functional independence (modified Rankin Scale [mRS] score 0-2), and functional improvement (shift in mRS score) at 3 months. The association between RI and the risk of recurrent stroke was evaluated with multivariate competing-risk regression analyses.ResultsA total of 628 patients with ELVO (mean age 64.7 12.5 years, median NIH Stroke Scale score 17 points, 99 [15.8%] with RI) who underwent EVT were enrolled. After adjustment for other relevant variables, multivariate regression analysis indicated that RI was independently associated with functional independence (adjusted odds ratio 0.53, 95% confidence interval [CI] 0.29-0.96, p = 0.035) at 3 months but not with mortality or functional improvement. Multivariate competing-risk regression analysis showed that patients with RI who received EVT had a significantly higher risk of recurrent stroke (adjusted hazard ratio 2.56, 95% CI 1.27-5.18, p = 0.009) compared to those with normal renal function.ConclusionOur results suggest that RI is an independent predictor of functional independence at 3 months and long-term risk of recurrent stroke in patients with ELVO treated with EVT.

Relationship between elevated plasma trimethylamine N-oxide levels and increased stroke injury

期刊: NEUROLOGY, 2020; 94 (7)

Objective To investigate whether elevated plasma trimethylamine N-oxide (TMAO) levels are associated with initial stroke severity and infarct volume. Methods This cross-sectional study included 377 patients with acute ischemic stroke and 50 healthy controls. Plasma TMAO levels were assessed at admission. Stroke infarct size and clinical stroke severity were measured with diffusion-weighted imaging and the NIH Stroke Scale (NIHSS). Mild stroke was defined as an NIHSS score < 6. Results Plasma TMAO levels were higher in patients with ischemic stroke than in healthy controls (median 5.1 vs 3.0 mu mol/L; p < 0.001). Every 1-mu mol/L increase in TMAO was associated with a 1.13-point increase in NIHSS score (95% confidence interval [CI] 1.04-1.29; p < 0.001) and 1.69-mL increase in infarct volume (95% CI 1.41-2.03; p < 0.001) after adjustment for vascular risk factors. At admission, 159 patients (42.2%) had experienced a mild stroke, and their plasma TMAO levels were lower compared to those with moderate to severe stroke (median 3.6 vs 6.5 mu mol/L; p < 0.001). The area under the receiver operating characteristics curve of plasma TMAO level in predicting moderate to severe stroke was 0.794 (95% CI 0.748-0.839; p < 0.001), and the optimal cutoff value was 4.95 mu mol/L. The sensitivity and specificity of TMAO levels >= 4.95 mu mol/L for moderate to severe stroke were 70.2% and 79.9%, respectively. Conclusions Patients with ischemic stroke had higher plasma TMAO levels compared to healthy controls. Higher plasma TMAO level at admission is an independent predictor of stroke severity and infarct volume in patients with acute ischemia.

Predictive role of heterozygous p.R4810K of RNF213 in the phenotype of Chinese moyamoya disease

期刊: NEUROLOGY, 2020; 94 (7)

ObjectivePrecise genetic analyses were conducted with ring finger protein 213 (RNF213) in relation to a particular clinical phenotype in Chinese patients with moyamoya disease (MMD) to determine whether heterozygosity is responsible for the early-onset and severe form of this disease.MethodsA case-control study for RNF213 p.R4810K involving 1,385 Chinese patients with MMD and 2,903 normal control participants was performed. Correlation analyses between genotype and phenotype or different clinical features were also statistically explored.ResultsAn obvious trend was observed: the carrying rate of RNF213 p.R4810K gradually decreased when moving from coastal cities in northeast, north, and east China to southern cities or inland areas. Higher frequencies of p.R4810K were observed in patients with MMD compared with control participants (odds ratio, 48.1; 95% confidence interval, 29.1-79.6; p = 1.6 x 10(-141)). In addition, the onset age of all patients with the GA and AA genotypes were lower than with the GG genotype, and the median onset age was 40.0, 36.0, and 11.5 years with GG, GA, and AA, respectively, thereby confirming that those with GA or AA could acquire MMD during early life stages. Patients with MMD with the GA genotype were more susceptible to posterior cerebral artery (PCA) involvement compared to those with the GG genotype (38.4% vs 23.3%, p = 8.3 x 10(-7)).ConclusionsStrong evidence suggests that the carrying rate of RNF213 p.R4810K is closely related MMD risk in China and has given rise to an earlier onset age and more severe PCA involvement.

Teaching NeuroImages: Pathology and thromboembolism of carotid web

期刊: NEUROLOGY, 2020; 94 (7)

A 43-year-old woman without relevant medical history presented with acute middle cerebral artery (MCA) occlusion (figure 1A). Thrombophilia and vasculitis were ruled out and echocardiography was normal. Carotid web was considered because a shelf-like protrusion arising from the left carotid bulb (figure 1C) was found, which is suspected as the cause of embolization in MCA.(1) Carotid endarterectomy was performed. The diaphragm-like structure demonstrated smooth muscle cell-rich intima, increased elastic tissue, and myxoid degeneration (figure 2, A and B). The superimposed thrombosis was identified in the web pocket (figure 2C). Postoperative CT angiography showed spontaneous recanalization of left MCA (figure 1B).

Questionnaire-based diagnosis of benign paroxysmal positional vertigo

期刊: NEUROLOGY, 2020; 94 (9)

ObjectivesTo develop a simple questionnaire for self-diagnosis of benign paroxysmal positional vertigo (BPPV).MethodsWe developed a questionnaire that consisted of 6 questions, the first 3 to diagnose BPPV and the next 3 to determine the involved canal and type of BPPV. From 2016 to 2017, 578 patients with dizziness completed the questionnaire before the positional tests, a gold standard for diagnosis of BPPV, at the Dizziness Clinic of Seoul National University Bundang Hospital.ResultsOf the 578 patients, 200 were screened to have BPPV and 378 were screened to have dizziness/vertigo due to disorders other than BPPV. Of the 200 patients with a questionnaire-based diagnosis of BPPV, 160 (80%) were confirmed to have BPPV with positional tests. Of the 378 patients with a questionnaire-based diagnosis of non-BPPV, 24 (6.3%) were found to have BPPV with positional tests. Thus, the sensitivity, specificity, and precision of the questionnaires for the diagnosis of BPPV were 87.0%, 89.8%, and 80.0% (121 of 161, 95% confidence interval 74.5%-85.5%). Of the 200 patients with a questionnaire-based diagnosis of BPPV, 30 failed to respond to the questions 4 through 6 to determine the involved canal and type of BPPV. The questionnaire and positional tests showed the same results for the subtype and affected side of BPPV in 121 patients (121 of 170, 71.2%).ConclusionThe accuracy of questionnaire-based diagnosis of BPPV is acceptable.Classification of evidenceThis study provides Class III evidence that, in patients with dizziness, a questionnaire can diagnose BPPV with a sensitivity of 87.0% and a specificity of 89.8%.

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