Background: Major intracerebral hemorrhage (ICH) trials have largely been unable to demonstrate therapeutic benefit in improving functional outcomes. This may be partly due to the heterogeneity of ICH outcomes based on their location, where a small strategic ICH could be debilitating, thus confounding therapeutic effects. We aimed to determine the ideal hematoma volume cutoff for different ICH locations in predicting ICH outcomes. Methods: We retrospectively analyzed consecutive ICH patients enrolled in the University of Hong Kong prospective stroke registry from January 2011 to December 2018. Patients with premorbid modified Rankin Scale score >2 or who underwent neurosurgical intervention were excluded. ICH volume cutoff, sensitivity, and specificity in predicting respective 6-month neurological outcomes (good [modified Rankin Scale score 0–2], poor [modified Rankin Scale score 4–6], and mortality) for specific ICH locations were determined using receiver operating characteristic curves. Separate multivariate logistic regression models were also conducted for each location-specific volume cutoff to determine whether these cutoffs were independently associated with respective outcomes. Results: Among 533 ICHs, the volume cutoff for good outcome according to ICH location was 40.5 mL for lobar, 32.5 mL for putamen/external capsule, 5.5 mL for internal capsule/globus pallidus, 6.5 mL for thalamus, 17 mL for cerebellum, and 3 mL for brainstem. ICH smaller than the cutoff for all supratentorial sites had higher odds of good outcomes (all P <0.05). Volumes exceeding 48 mL for lobar, 41 mL for putamen/external capsule, 6 mL for internal capsule/globus pallidus, 9.5 mL for thalamus, 22 mL for cerebellum, and 7.5 mL for brainstem were at greater risk of poor outcomes (all P <0.05). Mortality risks were significantly higher for volumes that exceeded 89.5 mL for lobar, 42 mL for putamen/external capsule, and 21 mL for internal capsule/globus pallidus (all P 0.8), except in predicting good outcome for cerebellum. Conclusions: ICH outcomes differed with location-specific hematoma size. Location-specific volume cutoff should be considered in patient selection for ICH trials.

Background: Recent trials have shown that low‐density lipoprotein cholesterol (LDL‐C) <1.80 mmol/L (<70 mg/dL) is associated with a reduced risk of major adverse cardiovascular events in White patients with ischemic stroke with atherosclerosis. However, it remains uncertain whether the findings can be generalized to Asian patients, or that similar LDL‐C targets should be adopted in patients with stroke without significant atherosclerosis. Methods and Results: We performed a prospective cohort study and recruited consecutive Chinese patients with ischemic stroke with magnetic resonance angiography of the intra‐ and cervicocranial arteries performed at the University of Hong Kong between 2008 and 2014. Serial postevent LDL‐C measurements were obtained. Risk of major adverse cardiovascular events in patients with mean postevent LDL‐C <1.80 versus ≥1.80 mmol/L, stratified by presence or absence of significant (≥50%) large‐artery disease (LAD) and by ischemic stroke subtypes, were compared. Nine hundred four patients (mean age, 69±12 years; 60% men) were followed up for a mean 6.5±2.4 years (mean, 9±5 LDL‐C readings per patient). Regardless of LAD status, patients with a mean postevent LDL‐C <1.80 mmol/L were associated with a lower risk of major adverse cardiovascular events (with significant LAD: multivariable‐adjusted subdistribution hazard ratio, 0.65; 95% CI, 0.42–0.99; without significant LAD: subdistribution hazard ratio, 0.53; 95% CI, 0.32–0.88) (both P <0.05). Similar findings were noted in patients with ischemic stroke attributable to large‐artery atherosclerosis (subdistribution hazard ratio, 0.48; 95% CI, 0.28–0.84) and in patients with other ischemic stroke subtypes (subdistribution hazard ratio, 0.64; 95% CI, 0.43–0.95) (both P <0.05). Conclusions: A mean LDL‐C <1.80 mmol/L was associated with a lower risk of major adverse cardiovascular events in Chinese patients with ischemic stroke with and without significant LAD. Further randomized trials to determine the optimal LDL‐C cutoff in stroke patients without significant atherosclerosis are warranted.

Stroke is one of the most common causes of adult-onset epilepsy. We aimed to develop a model to predict poststroke epilepsy (PSE) after a first-ever ischemic stroke, incorporating neuroimaging features of incident stroke. We analyzed clinical and neuroimaging features of patients with first-ever acute ischemic stroke consecutively admitted to Massachusetts General Hospital, United States. We performed competing risk regression with all-cause mortality as a competing event and derived the final multivariable model using backward stepwise elimination by the Akaike Information Criterion. We externally validated the model in 3 international cohorts in Hong Kong (Queen Mary Hospital [HK-QMH], Ruttonjee Hospital [HK-RH]) and Japan (National Cerebral and Cardiovascular Center) by discrimination and calibration and compared its performance with the SeLECT and SeLECT2.0 scores. We included a final derivative cohort of 1,436 patients with a mean age of 67.4 years and a slight male predominance (54.7%), along with a total of 2,534 patients in the validation cohorts. PSE, defined as the occurrence or recurrence of unprovoked seizure >7 days after stroke, occurred in 5.5% of the overall study population. Six variables (infarct size [Is], cortical involvement [C], hemorrhagic transformation [H], early seizures [E], MCA involvement [Mi], and age younger than 65 [A]) were independent predictors included in the final model and formed the IsCHEMiA score. Model discrimination was consistent across all cohorts, with c-statistics of 0.870 (United States), 0.852 (HK-QMH), 0.857 (HK-RH), and 0.826 (Japan). The model was well calibrated at 1 and 3 years after stroke in the overall validation cohort. The IsCHEMiA score improved the prediction of PSE compared with SeLECT in all cohorts and the overall study population (c-statistic 0.848 vs 0.782, z = 5.170, p < 0.0001). For example, an IsCHEMiA score of 3 predicts a low risk of PSE at 1 year (2%) and 5 years (6%) while an IsCHEMiA score ≥8 predicts a high risk at 1 year (67%) and 5 years (78%). The IsCHEMiA score is an improved and readily applicable predictive model developed and validated using international stroke cohorts in the modern era of reperfusion therapies. It serves as a foundation for personalized management and may guide future clinical trials on antiepileptogenic therapies in acute ischemic stroke.

Background: Intracerebral hemorrhage (ICH) survivors are at high risk for recurrent stroke and cardiovascular events. Blood pressure (BP) control represents the most potent intervention to lower these risks, but optimal treatment targets in this patient population remain unknown. We sought to determine whether survivors of ICH achieving more intensive BP control than current guideline recommendations (systolic BP <130 mmHg and diastolic BP <80 mmHg) were at lower risk of major adverse cardiovascular and cerebrovascular events and mortality. Methods: We analyzed data for 1828 survivors of spontaneous ICH from 2 cohort studies. Follow-up BP measurements were recorded 3 and 6 months after ICH, and every 6 months thereafter. Outcomes of interest were major adverse cardiovascular and cerebrovascular events (recurrent ICH, incident ischemic stroke, myocardial infarction), vascular mortality (defined as mortality attributed to recurrent ICH, ischemic stroke, or myocardial infarction), and all-cause mortality. Results: During a median follow-up of 46.2 months, we observed 166 recurrent ICH, 68 ischemic strokes, 69 myocardial infarction, and 429 deaths. Compared with survivors of ICH with systolic BP 120 to 129 mmHg, participants who achieved systolic BP 75 years or with modified Rankin Scale score 4 to 5, systolic BP <120 mmHg was associated with increased all-cause mortality (AHR, 1.38 [95% CI, 1.02–1.85] and AHR, 1.36 [95% CI, 1.03–1.78], respectively), but not vascular mortality. We found no differences in outcome rates between survivors of ICH with diastolic BP <70 versus 70 to 79 mmHg. Conclusions: Targeting systolic BP <120 mmHg in select groups of survivors of ICH could result in decreased major adverse cardiovascular and cerebrovascular events risk without increasing mortality. Our findings warrant investigation in dedicated randomized controlled trials.

Background: Recent intensive low-density lipoprotein cholesterol (LDL-C) lowering trials, including FOURIER, ODYSSEY OUTCOMES, and Treat Stroke to Target (TST) trials, have mostly refuted the concern surrounding statin use, LDL-C lowering, and intracerebral hemorrhage (ICH) risk. However, the results from these trials may not be fully applied to ICH survivors, as the populations studied were mainly patients without prior ICH, in whom the inherent ICH risk is more than 10 times lower than that of ICH survivors. Although available literature on statin use after ICH has demonstrated no excess risk of recurrent ICH, other potential factors that may modify ICH risk, especially hypertension control and ICH etiology, have not generally been considered. Notably, data on LDL-C levels following ICH are lacking. Aims: We aim to investigate the association between LDL-C levels and statin use with ICH risk among ICH survivors, and to determine whether the risk differed with patients’ characteristics, especially ICH etiology. Methods: Follow-up data of consecutive spontaneous ICH survivors enrolled in the University of Hong Kong prospective stroke registry from 2011 to 2019 were retrospectively analyzed. ICH etiology was classified as cerebral amyloid angiopathy (CAA) using the modified Boston criteria or hypertensive arteriopathy, while the mean follow-up LDL-C value was categorized as <1.8 or ⩾1.8 mmol/L. The primary endpoint was recurrent ICH. The association of LDL-C level and statin use with recurrent ICH was determined using multivariable Cox regression. Pre-specified subgroup analyses were performed, including based on ICH etiology and statin prescription. Follow-up blood pressure was included in all the regression models. Results: In 502 ICH survivors (mean age = 64.2 ± 13.5 years, mean follow-up LDL-C = 2.2 ± 0.6 mmol/L, 28% with LDL-C <1.8 mmol/L), 44 had ICH recurrence during a mean follow-up of 5.9 ± 2.8 years. Statin use after ICH was not associated with recurrent ICH (adjusted hazard ratio (AHR) = 1.07, 95% confidence interval (CI) = 0.57–2.00). The risk of ICH recurrence was increased for follow-up LDL-C <1.8 mmol/L (AHR = 1.99, 95% CI = 1.06–3.73). This association was predominantly observed in ICH attributable to CAA (AHR = 2.52, 95% CI = 1.06–5.99) and non-statin users (AHR = 2.91, 95% CI = 1.08–7.86). Conclusion: The association between post-ICH LDL-C <1.8 mmol/L and recurrent ICH was predominantly observed in CAA patients and those with intrinsically low LDL-C (non-statin users). While statins can be safely prescribed in ICH survivors, LDL-C targets should be individualized and caution must be exercised in CAA patients.

: Background: Uncontrolled blood pressure (BP) in intracerebral hemorrhage (ICH) survivors is common and associated with adverse clinical outcomes. We investigated whether characteristics of the ICH itself were associated with uncontrolled BP at follow-up. Methods: Subjects were consecutive patients aged ⩾18 years with primary ICH enrolled in the prospective longitudinal ICH study at Massachusetts General Hospital between 1994 and 2015. We assessed the prevalence of uncontrolled BP (mean BP ⩾140/90 mmHg) 6 months after index event. We used multivariable logistic regression models to assess the effect of hematoma location, volume, and event year on uncontrolled BP. Results: Among 1492 survivors, ICH was lobar in 624 (42%), deep in 749 (50%), cerebellar in 119 (8%). Lobar ICH location was associated with increased risk for uncontrolled BP after 6 months (OR 1.35; 95% CI [1.08–1.69]). On average, lobar ICH survivors were treated with fewer antihypertensive drugs compared to the rest of the cohort: 2.1 ± 1.1 vs 2.5 ± 1.2 (p < 0.001) at baseline and 1.8 ± 1.2 vs. 2.4 ± 1.2 (p < 0.001) after 6 months follow-up. After adjustment for the number of antihypertensive drugs prescribed, the association of lobar ICH location with risk of uncontrolled BP was eliminated. Conclusions: ICH survivors with lobar hemorrhage were more likely to have uncontrolled BP after 6 months follow-up. This appears to be a result of being prescribed fewer antihypertensive medications. Future treatment strategies should focus on aggressive BP control after ICH independent of hemorrhage location.