Cognitive Outcome after Acute Spontaneous Intracerebral Hemorrhage: Analysis of the iDEF Randomized Trial.

INTRODUCTION: The impact of intracerebral hemorrhage (ICH) on cognition and the determinants of cognitive recovery early after ICH remain elusive. In this post hoc analysis of the intracerebral hemorrhage deferoxamine (iDEF) trial, we examined the trajectories of cognitive impairment and the determinants of early cognitive recovery after ICH. METHODS: We examined baseline factors associated with a 90-day cognitive outcome and constructed generalized linear mixed models to examine the trajectory of cognitive function over time among iDEF participants. Cognition was measured by the Montreal Cognitive Assessment (MoCA) scores on days 7, 30, and 90. RESULTS: 291 were available for analysis under the trial's modified intention-to-treat definition (38% female, mean age 60.3 ± 12.0 years, median NIHSS 13, IQR 8-18). The median baseline ICH volume was 12.9 IQR (6.4-26.0) mL; 59 (20%) of the ICH cases were lobar, 120 (41%) had intraventricular extension. There was an overall significant increase in total MOCA score with time (p < 0.0001). Total MOCA score increased by an estimated 3.9 points (95% CI: 3.1, 4.7) between the day 7 and day 30 assessments and by an additional 2.9 points (95% CI: 2.2, 3.6) between the day 30 and day 90 assessments. Despite the overall improvement, 134 of 205 (65%) patients with an available 90-day MoCA score remained cognitively impaired with a score <26 on day 90. Older age, higher NIHSS score, baseline ICH volume, intraventricular hemorrhage, and perihematoma edema had an adjusted negative impact on cognitive recovery. CONCLUSIONS: Although ICH survivors exhibit significant improvement of cognitive status over the first 3 months, cognitive performance remains impaired in the majority of patients. Among factors independently associated with worse cognitive recovery, higher baseline ICH, intraventricular blood and perihematomal edema volumes, are potential therapeutic targets that merit further exploration.

Rationale and Design of the Statins Use in Intracerebral Hemorrhage Patients (SATURN) Trial.

INTRODUCTION: The benefits and risks of HMG-CoA reductase inhibitor (statin) drugs in survivors of intracerebral hemorrhage (ICH) are unclear. Observational studies suggest an association between statin use and increased risk of lobar ICH, particularly in patients with apolipoprotein-E (APOE) ε2 and ε4 genotypes. There are no randomized controlled trials (RCTs) addressing the effects of statins after ICH leading to uncertainty as to whether statins should be used in patients with lobar ICH who are at high risk for ICH recurrence. The SATURN trial aims to evaluate the effects of continuation versus discontinuation of statin on the risk of ICH recurrence and ischemic major adverse cerebro-cardio-vascular events (MACCE) in patients with lobar ICH. Secondary aims include the assessment of whether the APOE genotype modifies the effects of statins on ICH recurrence, functional and cognitive outcomes and quality of life. METHODS: The SATURN trial is a multi-center, pragmatic, prospective, randomized, open-label, Phase III clinical trial with blinded end-point assessment. A planned total of 1456 patients with lobar ICH will be recruited from 140 sites in the United States, Canada and Spain. Patients presenting within seven days of a spontaneous lobar ICH that occurred while taking a statin, will be randomized (1:1) to continuation (control) vs. discontinuation (intervention) of the same statin drug and dose that they were using at ICH onset. The primary outcome is the time to recurrent symptomatic ICH within a two-year follow-up period. The primary safety outcome is the occurrence of ischemic MACCE. CONCLUSION: The results will help to determine the best strategy for statin use in survivors of lobar ICH and may help to identify if there is a subset of patients who would benefit from statins.

Etiology of Primary Cerebellar Intracerebral Hemorrhage Based on Topographic Localization.

BACKGROUND: Cerebellar intracerebral hemorrhage (cICH) is often attributed to hypertension or cerebral amyloid angiopathy (CAA). However, deciphering the exact etiology can be challenging. A recent study reported a topographical etiologic relationship with superficial cICH secondary to CAA. We aimed to reexamine this relationship between topography and etiology in a separate cohort of patients and using the most recent Boston criteria version 2.0. METHODS: We performed a retrospective analysis of consecutive patients with primary cICH admitted to a tertiary academic center between 2000 and 2022. cICH location on brain computed tomography/magnetic resonance imaging scan(s) was divided into strictly superficial (cortex, surrounding white matter, vermis) versus deep (cerebellar nuclei, deep white matter, peduncular region) or mixed (both regions). Magnetic resonance imaging was rated for markers of cerebral small vessel disease. We assigned possible/probable versus absent CAA using Boston criteria 2.0. RESULTS: We included 197 patients; 106 (53.8%) were females, median age was 74 (63-82) years. Fifty-six (28%) patients had superficial cICH and 141 (72%) deep/mixed cICH. Magnetic resonance imaging was available for 112 (57%) patients (30 [26.8%] with superficial and 82 [73.2%] with deep/mixed cICH). Patients with superficial cICH were more likely to have possible/probable CAA (48.3% versus 8.6%; odds ratio [OR], 11.43 [95% CI, 3.26-40.05]; P<0.001), strictly lobar cerebral microbleeds (51.7% versus 6.2%; OR, 14.18 [95% CI, 3.98-50.50]; P<0.001), and cortical superficial siderosis (13.8% versus 1.2%; OR, 7.70 [95% CI, 0.73-80.49]; P=0.08). Patients with deep/mixed cICH were more likely to have deep/mixed cerebral microbleeds (59.2% versus 3.4%; OR, 41.39 [95% CI, 5.01-341.68]; P=0.001), lacunes (54.9% versus 17.2%; OR, 6.14 [95% CI, 1.89-19.91]; P=0.002), severe basal ganglia enlarged perivascular spaces (36.6% versus 7.1%; OR, 7.63 [95% CI, 1.58-36.73]; P=0.01), hypertension (84.4% versus 62.5%; OR, 3.43 [95% CI, 1.61 to -7.30]; P=0.001), and higher admission systolic blood pressure (172 [146-200] versus 146 [124-158] mm Hg, P<0.001). CONCLUSIONS: Our results suggest that superficial cICH is strongly associated with CAA whereas deep/mixed cICH is strongly associated with hypertensive arteriopathy.

An updated systematic review and meta-analysis investigating perihematomal edema and clinical outcome after intracerebral hemorrhage.

OBJECTIVES: The relationship between perihematomal edema (PHE) and intracerebral hemorrhage (ICH) outcomes is uncertain. Given newly published studies, we updated a previous systematic review and meta-analysis assessing the prognostic impact of PHE on ICH outcomes. MATERIALS AND METHODS: Databases were searched through September 2022 using pre-defined keywords. Included studies used regression to examine the association between PHE and functional outcome (assessed by modified Rankin Scale [mRS]) and mortality. The study quality was assessed using the Newcastle-Ottawa Scale. The overall pooled effect, and secondary analyses exploring different subgroups were obtained by entering the log transformed odds ratios and their confidence intervals into a DerSimonian-Laird random effects meta-analysis. RESULTS: Twenty-eight studies (n=8655) were included. The pooled effect size for overall outcome (mRS and mortality) was 1.05 (95% CI 1.03, 1.07; p<0.00). In secondary analyses, PHE volume and growth effect sizes were 1.03 (CI 1.01, 1.05) and 1.12 (CI 1.06, 1.19), respectively. Results of subgroup analyses assessing absolute PHE volume and growth at different time points were: baseline volume 1.02 (CI 0.98, 1.06), 72-hour volume 1.07 (CI 0.99, 1.16), growth at 24 hours 1.30 (CI 0.96, 1.74) and growth at 72 hours 1.10 (CI 1.04, 1.17). Heterogeneity across studies was substantial. CONCLUSIONS: This meta-analysis indicates that PHE growth, especially within the first 24 hours after ictus, has a stronger impact on functional outcome and mortality than PHE volume. Definitive conclusions are limited by the large variability of PHE measures, heterogeneity, and different evaluation time points between studies.