BACKGROUND: Branch atheromatous disease (BAD)–related stroke has emerged as a meaningful subtype of ischemic stroke yet remained understudied. We aimed to investigate the demographic, clinical, therapeutic, and prognostic characteristics of BAD-related stroke. METHODS: The BAD-study was a nationwide, multicenter, prospective, observational cohort study in 20 Chinese hospitals from June 2021 to June 2023, enrolling patients aged 18 to 80 years with BAD-related stroke within 72 hours of onset. Eligible single subcortical infarct in the territory of lenticulostriate artery and paramedian pontine artery was included. Clinical, laboratory, and treatment data were collected at baseline. The primary outcome was a proportion of good outcomes (modified Rankin Scale score, 0–2) at 90 days. Main secondary outcomes included early neurological deterioration (END), cerebrovascular event, major bleeding, and excellent outcome (modified Rankin Scale score, 0–1) during 90-day follow-up. RESULTS: We finally enrolled 476 patients, with a median age of 60 (interquartile range, 53–68) years, and 70.2% were male. The median National Institutes of Health Stroke Scale score was 3 (interquartile range, 2–6) at enrollment. Involvement of the lenticulostriate artery was more common than the paramedian pontine artery (60.7% versus 39.3%). END occurred in 14.7% of patients, with a median time from onset of 38 (interquartile range, 22–62) hours. The rates of good and excellent outcomes were 86.5% and 72%, respectively. Its 90-day stroke recurrence rate was 1.9%. Acute-phase therapy (from onset to 7 days of enrollment) showed heterogeneity and was not associated with prognosis. Multivariable logistic regression analysis identified the National Institutes of Health Stroke Scale score ≥4 at admission and END as negative predictors and extracranial artery stenosis as a positive predictor of good outcomes. Age ≥60 years, National Institutes of Health Stroke Scale score ≥4 at admission, and END were negative predictors of excellent outcomes. CONCLUSIONS: With distinct demographic, clinical, and prognostic characteristics, along with a high incidence of END and a low risk of stroke recurrence, BAD-related stroke could be categorized as a separate disease entity. Moreover, its acute-phase treatment strategies were undetermined, awaiting further high-quality studies.

Positioning a patient lying-flat in the acute phase of ischaemic stroke may improve recovery and reduce disability, but such a possibility has not been formally tested in a randomised trial. We therefore initiated the Head Position in Stroke Trial (HeadPoST) to determine the effects of lying-flat (0°) compared with sitting-up (≥30°) head positioning in the first 24 hours of hospital admission for patients with acute stroke. We plan to conduct an international, cluster randomised, crossover, open, blinded outcome-assessed clinical trial involving 140 study hospitals (clusters) with established acute stroke care programs. Each hospital will be randomly assigned to sequential policies of lying-flat (0°) or sitting-up (≥30°) head position as a ‘business as usual’ stroke care policy during the first 24 hours of admittance. Each hospital is required to recruit 60 consecutive patients with acute ischaemic stroke (AIS), and all patients with acute intracerebral haemorrhage (ICH) (an estimated average of 10), in the first randomised head position policy before crossing over to the second head position policy with a similar recruitment target. After collection of in-hospital clinical and management data and 7-day outcomes, central trained blinded assessors will conduct a telephone disability assessment with the modified Rankin Scale at 90 days. The primary outcome for analysis is a shift (defined as improvement) in death or disability on this scale. For a cluster size of 60 patients with AIS per intervention and with various assumptions including an intracluster correlation coefficient of 0.03, a sample size of 16,800 patients at 140 centres will provide 90 % power (α 0.05) to detect at least a 16 % relative improvement (shift) in an ordinal logistic regression analysis of the primary outcome. The treatment effect will also be assessed in all patients with ICH who are recruited during each treatment study period. HeadPoST is a large international clinical trial in which we will rigorously evaluate the effects of different head positioning in patients with acute stroke. ClinicalTrials.gov identifier: NCT02162017 (date of registration: 27 April 2014); ANZCTR identifier: ACTRN12614000483651 (date of registration: 9 May 2014). Protocol version and date: version 2.2, 19 June 2014.

Objective: To investigate aquaporin‐4 antibody (AQP4‐IgG) dynamics and relapse risk in patients with seropositive neuromyelitis optica spectrum disorder treated with immunosuppressants.Methods: This observational cohort study with prospectively collected data included 400 neuromyelitis optica spectrum disorder patients seropositive for AQP4‐IgG and treated with immunosuppressants. Serum AQP4‐IgG was detected by fixed cell‐based assay every 6 months.Results: After treatment with immunosuppressants, 128 patients became AQP4‐IgG seronegative. The median time to become seronegative for 400 patients was 76.4 months (61.4 months, NA). Among those patients with negative change of AQP4‐IgG, the mean annualized relapse rate significantly decreased after patients became seronegative (0.20 vs 0.77, p < 0.001), and a positive correlation was observed between time to become seronegative and relapse (OR 1.018, 95% CI 1.001–1.035, p < 0.05). Independent risk factors for AQP4‐IgG becoming seronegative were older age at onset, initiation of immunosuppressants at onset, and shorter disease duration before maintenance therapy. Independent risk factors for relapse included younger age (≤46.4 years) at onset, poly‐system involvement in the first attack, and unchanged or increased AQP4‐IgG titer. The relapse risk was not associated with sex, combination with connective tissue disease, seropositivity for systemic autoimmune antibodies, or incomplete recovery from the first attack.Interpretation: Patients with younger age at onset, poly‐system involvement in the first attack, and unchanged or increased titer of AQP4‐IgG are most likely to experience relapse under treatment with immunosuppressants. Time to AQP4‐IgG becoming seronegative and change of AQP4‐IgG titer may become the surrogate efficacy biomarkers in clinical trials. ANN NEUROL 2023;93:1069–1081

Background: Lipoprotein(a) [Lp(a)] is a risk factor of coronary heart disease, however, its effects on stroke are less well-defined. Methods: We performed a single-center, retrospective case-control study in 1,953 and 196 ischemic stroke and hemorrhagic stroke in-hospital patients, respectively. Controls were healthy individuals that were matched for sex and age (±5 years) for the ischemic (1:1 ratio) and hemorrhagic (1:2 ratio) stroke. Lp(a) concentration was measured using the latex agglutination turbidimetric method. Logarithmic transformation and quartile categorization were applied to adjust for the skewed distribution of Lp(a). Conditional logistic regression models were used to assess the association between Lp(a) and stroke risk. Results: Median Lp(a) concentration was higher in stroke patients when compared with controls (12.2 vs. 8.60 mg/dL) and hemorrhagic strokes (14.40 vs. 13.40 mg/dL). The conditional multivariate analysis revealed a positive association between Lp(a) and ischemic stroke (OR =2.03, 2.36, and 2.03 for quartiles 2, 3 and 4, respectively, vs. quartile 1; P<0.001). In addition, elevated Lp(a) was also significantly associated with increased hemorrhagic stroke risk, after adjusted for potential covariates (OR =1.93, 3.24, and 2.19 for quartile 2, 3 and 4 respectively vs. quartile 1, P<0.05). The stratified analyses for ischemic and hemorrhagic stroke revealed significant association between elevated log-transformed Lp(a) and ischemic stroke in men. Furthermore, there was a trend towards a higher stroke risk for younger patients compared with older patients. Conclusions: Elevated serum Lp(a) is significantly positively correlated with ischemic and hemorrhagic stroke risk in the Chinese Han population, especially among men and younger patients.

Background: It was uncertain if direct endovascular thrombectomy (ET) was superior to bridging thrombolysis (BT) for patients with acute ischemic stroke caused by large‐vessel occlusions. We aimed to examine real‐world clinical outcomes of ET using nationwide registry data in China and to compare the efficacy and safety between BT and direct ET. Methods and Results: Patients treated with ET from a nationwide registry study in China were included. Rapid neurological improvement, intracranial hemorrhage, and in‐hospital mortality were compared between the 2 groups using multivariate logistic models and propensity‐score matching analyses. A total of 7674 patients from 592 stroke centers were included. The median onset‐to‐puncture time, onset‐to‐door time, and door to puncture time were 290, 170, and 99 minutes, respectively. A total of 2069 (27.0%) patients received BT treatment. Patients in the BT group had a significantly shorter onset‐to‐puncture time (235 versus 323 minutes; P <0.001) and onset‐to‐door time (90 versus 222 minutes; P <0.001) compared with the direct ET group. The prior use of intravenous thrombolysis was associated with a higher rate of rapid neurological improvement (adjusted odds ratio [OR], 0.83; 95% CI, 0.71–0.96) and higher risk of intracranial hemorrhage (adjusted OR, 1.46; 95% CI, 1.18–1.80) in multivariate analyses and propensity‐score matching analyses. Conclusions: This study reflects the current application of ET in China. More patients received direct ET than BT. Our results suggested that favorable short‐term outcomes could be achieved with BT compared with direct ET. Higher risk of intracranial hemorrhage was observed in the BT group.

Objective: The aim of this systematic review and meta-analysis was to provide evidence that biomarkers of large artery atherosclerosis, including arterial stenosis and greater carotid intima-media thickness (cIMT), may serve as clinical markers of subclinical haemorrhage-prone cerebral small vessel disease, reflected by cerebral microbleeds (CMBs). Methods: We searched PubMed, MEDLINE, Web of Science, EMBASE and the Cochrane Library to identify relevant studies published before 1 July 2016. The association between arterial stenosis and CMBs was estimated by the OR and 95% CI. The association of cIMT and CMBs was calculated using the standardised mean difference (SMD). Heterogeneity and publication bias were explored. Results: 8 studies including a total of 7160 participants were pooled in the meta-analysis. 6 of the included studies were cross-sectional, except that 2 were prospective. We found a significant association between arterial stenosis >50% and the presence of CMBs (OR 1.95, 95% CI 1.13 to 3.36, I²=56.1%). A fixed-effects model suggested that patients with CMBs were more likely to have a greater cIMT (SMD 0.20, 95% CI 0.11 to 0.28, I²=24.7%). Conclusions: This systematic review and meta-analysis found that there is a relationship between large artery atherosclerosis and CMBs. Future studies are needed to confirm the impact of atherosclerosis on the CMBs, which may have potential therapeutic implications.