Neurology最新文献

Background and objectives: Race and ethnicity are proxy measures of sociocultural factors that influence cognitive test performance. Our objective was to compare different regression-based cognitive normative models adjusting for demographics and different combinations of easily accessible/commonly used social determinants of health (SDoH) factors, which may help describe cognitive performance variability historically captured by ethnoracial differences.

Methods: We performed cross-sectional analyses on data from Black and White participants without mild cognitive impairment/dementia in the Atherosclerosis Risk in Communities Study who attended visit 5 in 2011-2013. Participants underwent a battery of 11 cognitive tests (3 domains: memory, executive function, language). We fit 6 separate normative models for each cognitive test, all including age and education, with different combinations of race, the Wide Range of Achievement Test (education quality proxy), and area deprivation index (neighborhood deprivation) associated with current residence. We compared model fits and calculated concordances/discordances between models using z-scores derived from each normative model and a z-score <-1.5 threshold for impairment.

Results: Participants (n = 2,392) had a mean age of 74.4 years, 60.4% were female, and 17.1% were of self-reported Black race. The "Full" model with race alongside demographic and SDoH measures consistently outperformed other nested submodels (likelihood ratios ≥ 100) for all domains/tests except Delayed Word Recall. Models with education quality alone ("WRAT") generally outperformed models with neighborhood deprivation ("ADI") or race ("Race") alone for memory and language tests while "Race" models performed better for executive function tests. Adding neighborhood deprivation to education quality ("WRAT + ADI") did not improve models vs using "WRAT" alone. Across all domains/tests, the concordance compared with the "Full" model was lower for "Education" and "ADI" models than for other nested models. Although numbers were small, there was greater discordance among Black (range = 8.2%-23.2%) compared with White (range = 2.2%-3.4%) participants, particularly for Boston Naming Test and executive function tests.

Discussion: Education quality outperformed neighborhood disadvantage as an additional/alternative SDoH measure in normative models and may be useful to collect in cognitive aging studies. While performance varied across cognitive domains and tests, routinely reported SDoH variables (education level, education quality, late-life neighborhood deprivation) did not fully account for observed ethnoracial variability; future work should evaluate SDoH across the lifespan in more ethnoracially diverse populations.

Background and objectives: Large vessel vasculopathy (LVV), or moyamoya syndrome, increases the risk of stroke in patients with sickle cell disease (SCD), yet effective treatments are lacking. In atherosclerotic carotid disease, previous studies demonstrated elevated oxygen extraction fraction (OEF) as a predictor of ipsilateral stroke. In a SCD cohort, we examined hemispheric hemodynamic and oxygen metabolic dysfunction as tissue-based biomarkers of cerebral ischemic risk in patients with LVV.

Methods: Children and adults with SCD were recruited from a SCD clinic associated with a tertiary medical center and underwent prospective brain MRI and MR angiography. LVV was defined as ≥75% stenosis in a major anterior circulation artery, excluding occlusion or previous revascularization surgery. Baseline characteristics, cerebral blood flow (CBF), normalized OEF (nOEF), infarct volume, white matter microstructure, and brain volume were compared in hemispheres with vs without LVV. In a cross-sectional analysis, mixed-effects linear multivariable models examined the effect of LVV on: (1) CBF and nOEF, as tissue markers of hemodynamic and oxygen metabolic stress, respectively, and (2) endpoints of cerebral ischemic injury including infarct volume, white matter microstructure, and brain volume.

Results: Of 155 patients (22 [12-31] years, 57% female), 33 (21%) had ≥25% stenosis, 22 (14%) had ≥50% stenosis, 14 (9%) had 75%-99% stenosis, and 5 (3%) had 100% occlusion. After excluding hemispheres with previous revascularization surgery, LVV was present in 16 hemispheres from 11 patients. Hemispheres with (N = 16) vs without (N = 283) LVV had lower CBF (25.2 vs 32.1 mL/100 g/min, p = 0.01) and higher nOEF (0.99 vs 0.95, p = 0.02). On multivariable analysis, CBF was nonsignificantly lower (β = -0.16, p = 0.07) while nOEF remained higher in hemispheres with LVV (β = 0.04, p = 0.03). Moreover, LVV was associated with greater hemispheric infarct volume, microstructural disruption, and atrophy.

Discussion: Beyond greater infarct burden, LVV was associated with hemispheric atrophy and white matter microstructural injury. As an indicator of active hypoxia, elevated nOEF likely represents a compensatory response to flow-limiting stenosis in hemispheres with LVV. The study is limited by a small number of patients with severe stenosis. Future studies are needed to evaluate the potential of tissue-based CBF and nOEF in assessing stroke risk and guide timely treatment of vasculopathy in SCD.

Background and objectives: Deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus (ANT) has been shown to be effective in treating some patients with medically refractory epilepsy. However, it remains unknown how seizures spread through the ANT relative to other thalamic nuclei. This study aimed to investigate, through simultaneous recordings from both ANT and pulvinar (PLV) nucleus, their roles in seizure propagation. Our goal was to determine whether the ANT is the primary site of seizure propagation in the human thalamus, especially for focal seizure originating in the medial temporal lobe.

Methods: In a retrospective design, we studied EEGs and clinical notes of patients with refractory epilepsy who were implanted with stereo-EEG (sEEG) electrodes across cortical regions, some of which were extended to reach various sites of the thalamus (i.e., multisite thalamic recordings). We selected patients from the Stanford Comprehensive Epilepsy Center with both ANT and PLV electrodes and collected information about the timing and anatomy of seizure activity in the seizure onset zones, usually temporal, and the 2 thalamic sites.

Results: We recruited 17 (5 female, mean age 32 years) adult patients with simultaneous ipsilateral ANT and PLV recordings. In all patients, the procedure was safe without any complications. In 100% of patients, the thalamus was involved during seizures (in 88% both ANT and PLV and in 82% first the PLV). In patients with confirmed hippocampal or amygdalar onset seizures, 62% had initial involvement and 100% had subsequent involvement of the PLV nucleus. Only 31% showed initial propagation to ANT. All focal-to-bilateral tonic-clonic seizures and most of the focal impaired awareness seizures had early involvement of both ANT and PLV, with rapid spread to the contralateral nuclei.

Discussion: sEEG of thalamic nuclei simultaneously provides an opportunity to understand propagation patterns of seizures with respect to each thalamic subdivision at the individual level. The patterns of seizure propagation, as we report here, provide insights about the prominent involvement of the PLV nucleus during seizure propagation. This may motivate future prospective work in larger cohorts of patients to understand how thalamic propagation may predict response to resective/ablative surgery or whether personalization of DBS (for instance, PLV instead of, or together with, ANT) could improve clinical outcomes.

Background and objectives: Acute stroke is associated with a spectrum of functional deficits. The objective of this analysis was to explore whether the importance of individual risk factors differ by stroke severity, which may be of relevance to public health strategies to reduce disability.

Methods: INTERSTROKE is an international case-control study of risk factors of first acute stroke (recruitment 2007-August 2015) in 32 countries. Stroke severity was measured using the modified Rankin Scale (mRS) score within 72 hours of admission to hospital. Severe stroke is defined as mRS scores of 4-6 (and non-severe stroke, score of 0-3). We used multinomial logistic regression to estimate comparative odds ratios (ORs; 95% CIs) for severe and non-severe stroke and tested for heterogeneity (p_{heterogeneity}). We also conducted a matched case-case analysis (matched for age, sex, country, and primary stroke subtype) to determine whether the prevalence of risk factors differed significantly between severe and non-severe stroke. A significant difference in the association of a risk factor of severe stroke compared with non-severe stroke was defined as p < 0.05 for both p_{heterogeneity} and p_case-case.

Results: Of patients with acute stroke (n = 13,460), 64.0% (n = 8,612) were reported to have mRS scores of 0-3 and 36.0% (n = 4,848) scores of 4-6. The mean age was 61.7 years for patients with non-severe stroke and 62.9 years for patients with severe stroke (p = 0.72). 38.1% (n = 3,278) of patients with non-severe stroke and 44.6% (n = 2,162) of patients with severe stroke were female. Hypertension (OR 3.21; 95% CI 2.97-3.47 for severe stroke, OR 2.87; 95% CI 2.69-3.05 for non-severe stroke; p_{heterogeneity} = 0.03; p_case-case < 0.001), atrial fibrillation (OR 4.70; 95% CI 4.05-5.45 for severe stroke, OR 3.61; 95% CI 3.16-4.13 for non-severe stroke; p_{heterogeneity} = 0.009; p_case-case < 0.001), and smoking (OR 1.87; 95% CI 1.72-2.03 for severe stroke, OR 1.65; 95% CI 1.54-1.77 for non-severe stroke; p_{heterogeneity} = 0.02; p_case-case < 0.001) had a stronger association with severe stroke, compared with non-severe stroke. The waist-to-hip ratio had a stronger association with non-severe stroke compared with severe stroke (p_{heterogeneity} < 0.001; p_case-case < 0.001).

Discussion: Hypertension, atrial fibrillation, and smoking had a stronger magnitude of association with severe stroke (compared with non-severe stroke) while the increased waist-to-hip ratio had a stronger magnitude of association with non-severe stroke.

Background and objectives: Although dexmedetomidine (DEX) is widely administered during endovascular treatment (EVT) to enhance procedural adherence of patients with acute ischemic stroke (AIS) with large vessel occlusion, there is limited research on the association of DEX and outcomes among these patients. Hence, this study aimed to explore the safety and outcomes of DEX during conscious sedation (CS) in a real-world setting among patients undergoing EVT.

Methods: This study was an individual patient-level pooled analysis of 2 multicenter randomized clinical trials RESCUE-BT and DEVT. This study included patients who underwent EVT because of occlusion of the internal carotid artery or middle cerebral artery. The DEX group included those receiving intraprocedural DEX for CS, whereas the patients without intraprocedural DEX sedation were categorized into the non-DEX group. The primary outcome was functional independence (modified Rankin Scale score of 0-2 at 90 days). Adjusted odds ratio (aOR) and 95% CI were obtained by logistic regression models.

Results: A total of 728 patients were included in this study, of whom 308 (42.3%) were female. The median (interquartile range) age was 69 (59-76) years; the median baseline NIH Stroke Scale score was 16 (12-19). Compared with the non-DEX group, the DEX group had a significantly lower rate of functional independence (40.3% vs 51.3%; aOR 0.66; 95% CI 0.46-0.93; p = 0.019). There was a significantly higher rate of unstable procedural hemodynamics in the DEX group (9.7% vs 2.3%; aOR 4.60, 95% CI 2.12-9.99, p < 0.001). In subgroup analysis, similar results were found in intraprocedural DEX-treated patients when compared with local anesthesia or intraprocedural midazolam-treated patients, respectively.

Discussion: There was a negative association between procedural DEX administration during CS and functional outcomes in patients with AIS receiving EVT in a real-world setting. A larger cohort is warranted to validate our findings.

Classification of evidence: This study provides Class II evidence that the use of DEX during EVT of AIS is associated with a worse outcome compared with other agents.

A 50-year-old male patient presented with a 10-year history of progressive cerebellar ataxia, multifocal dystonia with dystonic tremors, and oculomotor abnormalities including bilateral ptosis, slow saccades, and reduced range of ocular movements. There were no signs of cognitive impairment, parkinsonism, autonomic dysfunction, or muscle weakness, and the family history was unremarkable. This case presents the diagnostic approach to adult-onset cerebellar ataxia with dystonia and abnormal eye movements. In this era of genomic testing, our case highlights the role of clinical phenotyping and the utility of whole-exome sequencing in ataxias.