Survivors Of Primary Intracerebral Hemorrhage Research Articles

Abstract P878: Racial and Ethnic Disparities in Early Hypertension Control After Intracerebral Hemorrhage

Introduction: Survivors of Intracerebral Hemorrhage (ICH) are at high risk of recurrent stroke. This risk is inversely proportional to average Blood Pressure (BP) after ICH. Racial/ethnic minority ICH survivors in the US demonstrate greater hypertension severity after ICH and are at higher risk of recurrent cerebral bleeding. Since most recurrent strokes occur within 12-18 months of index ICH, rapidly achieving BP control is likely to be crucial. We investigated the frequency, prognostic impact, and racial/ethnic disparities in uncontrolled short-term hypertension (HTN) after ICH. Methods: We analyzed data from prospective ICH cohort studies at Massachusetts General Hospital (MGH-ICH, n=1305) and the University of Hong Kong (HK-ICH, n=523). We classified HTN as controlled, uncontrolled or treatment-resistant and determined: 1) risk factors for uncontrolled and treatment-resistant HTN; and 2) whether HTN control at 3 months is associated with long-term BP control, stroke recurrence and mortality across self-reported race/ethnicity groups. Results: We followed 1828 ICH survivors (1128 White, 565 Asian, 59 Hispanic, 49 Black, 27 other) for a median of 46.2 months. Only 9 of 172 (5%) recurrent strokes occurred before 3 months after ICH. At 3 months, 713 participants (39%) had controlled HTN, 755 (41%) had undertreated HTN, and 360 (20%) had treatment-resistant HTN. BP measurements at 3 months were highly correlated with measurements during follow-up (p<0.001). Black, Hispanic and Asian race/ethnicity were associated with higher prevalence of uncontrolled HTN at 3 months (all p<0.05). Both undertreated and uncontrolled HTN at 3 months were associated with increased risk of recurrent stroke and mortality during follow-up (all p<0.05). Conclusions: Most ICH survivors have inadequate HTN control 3 months after ICH, with under-treatment accounting for the majority of cases. Three-month BP measurements are associated with inadequate long-term HTN control, higher recurrent stroke risk and mortality. ICH survivors self-reporting as Black, Hispanic or Asian appear to be at highest risk for uncontrolled HTN. Optimizing HTN control at 3 months is a unique opportunity to address racial/ethnic disparities in quality of care among survivors of primary ICH.

Association of Selective Serotonin Reuptake Inhibitor Use After Intracerebral Hemorrhage With Hemorrhage Recurrence and Depression Severity

Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat poststroke depression but are associated with increased incidence of first-ever intracerebral hemorrhage (ICH) in the general population. The decision to treat ICH survivors with SSRIs must therefore balance potential risks of ICH recurrence with presumed benefits on depressive symptoms. To determine whether SSRI use among survivors of primary ICH was associated with ICH recurrence and decreased severity of depressive symptoms. Longitudinal ICH cohort study at a tertiary care center enrolling from January 2006 to December 2017, with follow-up for a median of 53.2 months (interquartile range, 42.3-61.2 months). The study included 1279 consenting individuals (1049 White, 89 Black, 77 Hispanic, and 64 other race/ethnicity) of 1335 eligible patients presenting with primary ICH and who were discharged alive from initial hospitalization for stroke. We conducted univariable and multivariable analyses for ICH recurrence risk and depression severity, including subset analyses for patients with 1 or more of the following characteristics associated with high ICH recurrence risk: (1) lobar ICH; (2) presence of the apolipoprotein ε2/ε4 gene variants; (3) prior history of ICH/TIA/ischemic stroke; and (4) Black or Hispanic race/ethnicity. Mean age of study participants was 71.3 years, with 602 women (47%); of the 1279 participants, 1049 were White, 89 were Black, 77 were Hispanic, and 64 were other race/ethnicity. SSRI exposure was associated with both ICH recurrence (subhazard ratio [SHR], 1.31; 95% CI, 1.08-1.59) and resolution of post-ICH depression (SHR, 1.53; 95% CI, 1.12 2.09). Among those individuals at high risk for recurrent ICH, SSRIs were associated with further elevation in risk for ICH recurrence (SHR, 1.79; 95% CI, 1.22-2.64) compared with all other survivors of ICH (SHR, 1.20; 95% CI, 1.01-1.42; P = .008 for comparison of effect sizes). The association of SSRI with reduced depressive symptoms did not differ between high those at high risk for recurrent ICH and all other ICH survivors. Selective serotonin reuptake inhibitor exposure after ICH is associated with both improvement in depressive symptoms and increased risk of recurrent hemorrhagic stroke. Clinical history, neuroimaging data, and genetic biomarkers may help to identify survivors of ICH more likely to safely tolerate SSRI use.

Hypertension Severity, Race/Ethnicity and Stroke Recurrence Risk among Oldest Old Intracerebral Hemorrhage Survivors

Background Oldest old (age ≥80 years) survivors of Intracerebral Hemorrhage (ICH) may be at higher risk for stroke recurrence, reflecting increasing hypertension severity with aging. Because minority ICH survivors (African American and Hispanic) are at higher risk of stroke recurrence, oldest-old individuals in these racial/ethnic groups are likely to be at even higher risk. We sought to determine whether: 1) oldest old ICH survivors are at higher risk for stroke recurrence; and 2) minority oldest-old ICH survivors are at even higher risk for recurrent stroke than age-matched white counterparts. Methods We analyzed data from survivors of primary ICH, enrolled in two prospective studies (the ICH study at Massachusetts General Hospital and the Longitudinal Extension of the ERICH study). Exposures of interest include patients’ demographics (including self-reported race/ethnicity), medical history, ICH characteristics, Blood Pressure (BP) measurements and medications exposures during follow-up. Outcome of interest was recurrent stroke (i.e. ICH and/or ischemic stroke) during follow-up. Results We enrolled 1938 ICH survivors, including 507 aged ≥80 years (435 white, 38 African American, and 34 Hispanic) and 1431 aged Conclusion Oldest old ICH survivors, and specifically minority survivors age ≥80 years, are at higher risk for stroke recurrence and more likely to demonstrate inadequate blood pressure control. Future ICH studies will benefit from focusing on blood pressure control among oldest old survivors, with specific emphasis on African Americans.

Abstract TP428: Hypertension Severity and Stroke Recurrence Risk among Oldest Old Intracerebral Hemorrhage Survivors

Introduction: Oldest old (age ≥80 years) survivors of Intracerebral Hemorrhage (ICH) may be at higher risk for stroke recurrence, reflecting increasing hypertension severity with aging. Dedicated longitudinal studies of ICH in the oldest old are lacking, yet urgently needed as they represent an ever-increasing proportion of survivors. We sought to determine whether: 1) oldest old ICH survivors are at higher risk for stroke recurrence; 2) hypertension severity accounts for disparities in stroke recurrence risk across age categories. Methods: We analyzed data from survivors of primary ICH, enrolled in a single-center prospective study. Exposures of interest include patients’ demographics, medical history, ICH characteristics, Blood Pressure (BP) measurements and medications exposures during follow-up. Outcomes of interest included ICH and/or ischemic stroke events during follow-up. Results: We enrolled 1464 ICH survivors (441 ≥80 years and 1023 <80 years). In multivariable analyses lobar ICH location, white non-Hispanic background and female gender were independently associated with ICH at age ≥80 years (all p<0.05). ICH survivors age ≥80 years had higher systolic BP during follow-up (≥80 years: median 148 mmHg, IQR 139-156 vs. <80 years: median 138, IQR 132-145, p<0.001), but they were less likely to receive anti-hypertensive treatment (≥80 years: 233/442, 53% vs <80 years: 603/1023, 59%, p=0.003). Hypertension severity interacted with advancing age (interaction p<0.001) to further increase stroke recurrence risk among oldest old ICH survivors with frank hypertension (Figure 1). Conclusion: Oldest old ICH survivors are more likely to be female, white non-Hispanic, to present with lobar ICH, and to demonstrate inadequate blood pressure control. They are at higher risk for stroke recurrence, with hypertension severity playing a pivotal role. Future ICH studies will benefit from focusing on blood pressure control among oldest old survivors.

Editors' note: Poststroke epilepsy in long-term survivors of primary intracerebral hemorrhage

In “Poststroke epilepsy in long-term survivors of primary intracerebral hemorrhage,” Lahti et al. investigated the incidence and predisposing factors for development of poststroke epilepsy (PSE) after primary intracerebral hemorrhage (PICH) during a long-term follow-up. In this retrospective study, they found that 83/615 intracerebral hemorrhage (ICH) patients (13.5%) developed PSE. In their analysis, they found that subcortical hematoma location and early seizures increased the risk of PSE after PICH in long-term survivors, while hypertension seemed to reduce the risk. In response to this article, Dr. Zelano shares similar results of his study looking at a registry of 10,195 patients with ICH, out of whom 12.4% developed PSE over a median follow-up time of 4.8 years. In “Poststroke epilepsy in long-term survivors of primary intracerebral hemorrhage,” Lahti et al. investigated the incidence and predisposing factors for development of poststroke epilepsy (PSE) after primary intracerebral hemorrhage (PICH) during a long-term follow-up. In this retrospective study, they found that 83/615 intracerebral hemorrhage (ICH) patients (13.5%) developed PSE.

Author response: Poststroke epilepsy in long-term survivors of primary intracerebral hemorrhage.

We thank Dr. Zelano for the comments on our article1 and for bringing his study to our attention. The results from this register-based Swedish cohort study2 were unavailable: the article could not be found through PubMed or MEDLINE searches, and was published online shortly before our manuscript was sent for review.

Reader response: Poststroke epilepsy in long-term survivors of primary intracerebral hemorrhage.

I read with interest the article by Lahti et al.1 on the incidence of poststroke epilepsy (PSE) in 615 intracerebral hemorrhage (ICH) survivors, out of whom 13% developed PSE during a median follow-up of 6.4 years. The article is very interesting and in line with the emerging notion that PSE is more common than previously thought. However, the authors were mistaken in their statement that long-term incidence of PSE after ICH had not been previously investigated.

Spotlight on the June 6 issue

#### Notable in Neurology This issue features an article that evaluates the burden of deep and lobar lacunes in intracerebral hemorrhage due to cerebral amyloid angiopathy and hypertensive small vessel disease, and another that investigates the involvement of human leukocyte antigen loci in aromatic antiepileptic drug-induced cutaneous adverse reactions. A featured article examines placebo and nocebo responses in restless legs syndrome. ### Poststroke epilepsy in long-term survivors of primary intracerebral hemorrhage![Graphic][1] In a long-term follow-up study, the authors sought … [1]: /embed/inline-graphic-1.gif

Poststroke epilepsy in long-term survivors of primary intracerebral hemorrhage.

To identify the incidence and predisposing factors for development of poststroke epilepsy (PSE) after primary intracerebral hemorrhage (PICH) during a long-term follow-up. We performed a retrospective study of patients who had had their first-ever PICH between January 1993 and January 2008 in Northern Ostrobothnia, Finland, and who survived for at least 3 months. These patients were followed up for PSE. The associations between PSE occurrence and sex, age, Glasgow Coma Scale (GCS) score on admission, hematoma location and volume, early seizures, and other possible risk factors for PSE were assessed using the Cox proportional hazards regression model. Of the 615 PICH patients who survived for longer than 3 months, 83 (13.5%) developed PSE. The risk of new-onset PSE was highest during the first year after PICH with cumulative incidence of 6.8%. In univariable analysis, the risk factors for PSE were early seizures, subcortical hematoma location, larger hematoma volume, hematoma evacuation, and a lower GCS score on admission, whereas patients with infratentorial hematoma location or hypertension were less likely to develop PSE (all variables p < 0.05). In multivariable analysis, we found subcortical location (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.35-3.81, p < 0.01) and early seizures (HR 3.63, 95% CI 1.99-6.64, p < 0.01) to be independent risk factors, but patients with hypertension had a lower risk of PSE (HR 0.54, 0.35-0.84, p < 0.01). Subcortical hematoma location and early seizures increased the risk of PSE after PICH in long-term survivors, while hypertension seemed to reduce the risk.

Abstract TMP113: Long-term Cognitive Decline After Intracerebral Hemorrhage

Introduction: Cerebral small vessel disease (CSVD) is the leading cause of Vascular Cognitive Impairment (VCI). Although Intracerebral Hemorrhage (ICH) is the most severe manifestation of CSVD, VCI among ICH survivors has been the subject of limited investigations. Hypothesis: We sought to test these hypotheses: 1) long-term cognitive decline rates are substantial even among initially non-demented ICH survivors; 2) underlying CSVD plays a substantial role in determining post-ICH long-term cognitive decline. Methods: We enrolled survivors of primary ICH, with no evidence of dementia 6 months post-hemorrhage, in a single-center longitudinal observational study. Presence and severity of CSVD was assessed at enrollment using two established markers of CSVD on CT (CT-defined white hatter hypodensity [CT-WMH]) and MRI (cerebral microbleeds [CMBs]). We captured blood pressure measurements during follow-up via review of medical records. Cognitive performance was assessed using the Modified Telephone Interview for Cognitive Status (TICS-m), a standardized validated telephone-based cognitive battery. We constructed multivariate models of cognitive decline rate, defined as slope of TICS-m scores over time. Results: A total of 275 ICH survivors qualified for inclusion in our analyses; of these 83 (30%) developed incident dementia and 33 (12%) developed incident Mild Cognitive Impairment (MCI) at 5 years (Figure). CSVD imaging markers were associated with cognitive decline rate (CT-WMH: p=0.001, CMBs: p=0.003), as were pulse pressure (p=0.003) and systolic blood pressure variation coefficient (p=0.034). Conclusions: Long-term cognitive decline is frequent and substantial among ICH survivors not demented at time of ICH, and strongly associates with severity of underlying CSVD. Our findings suggest that it is the extent of CSVD and not particular ICH characteristics that are most associated with long-term cognitive decline in survivors of ICH.

Antiplatelet use after intracerebral hemorrhage

Survivors of intracerebral hemorrhage are at risk for recurrent intracerebral hemorrhage and ischemic cardiovascular and cerebrovascular disease. To determine whether antiplatelet therapy increases the risk of recurrent intracerebral hemorrhage. The authors reviewed data from consecutive survivors of primary intracerebral hemorrhage enrolled in a single-center prospective cohort study. Survivors were followed by telephone interview; recurrent intracerebral hemorrhage and post-index antiplatelet agent use and duration were recorded. Cox proportional hazards models was used with antiplatelet agent exposure as a time-dependent variable to assess the effect of antiplatelet agent use on recurrent intracerebral hemorrhage, stratified by lobar and deep hemispheric location. Recurrent intracerebral hemorrhage was more common in survivors of lobar hemorrhage compared with survivors of deep hemorrhage (cumulative 2-year rate 22% vs 4%; p = 0.007). Antiplatelet agents were prescribed in 22% of intracerebral hemorrhage survivors (27/127 lobar, 19/80 deep hemispheric), most commonly for prevention of ischemic heart disease. Antiplatelet agent use was not associated with intracerebral hemorrhage recurrence in survivors of either lobar hemorrhage (hazard ratio [HR] 0.8, 95% CI 0.3 to 2.3, p = 0.73) or of deep hemorrhage (HR 1.2, 95% CI 0.1 to 14.3, p = 0.88). Antiplatelet agent use is relatively common following intracerebral hemorrhage but did not appear to be associated with a large increased risk of intracerebral hemorrhage recurrence in this observational study.

Rate of stroke recurrence in patients with primary intracerebral hemorrhage.

Primary intracerebral hemorrhage (PICH) is a devastating illness with high early mortality. Hypertension is a major risk factor both for ischemic cerebrovascular disease and for intracranial hemorrhage. Survivors of PICH are at risk for both recurrent hemorrhage and ischemic cerebrovascular disease. We sought to determine the rate of recurrence of ICH or cerebral ischemia in a cohort of PICH patients at the Toronto Hospital, Toronto, Canada. A retrospective search of computerized hospital records from 1986 to 1996 for patients with a discharge diagnosis of intracerebral hemorrhage (International Classification of Diseases, Ninth Revision-Clinical Modification [ICD-9-CM] code 431) was conducted to identify the index cases. Charts were abstracted for demographic and clinical characteristics. CT scans, MR scans, or radiologist reports were reviewed. To determine recurrence, the database was linked to the Ontario Provincial Government Vital Statistics Registry and to the Canadian Institute for Health Information database of hospital discharge abstracts. Logistic regression analysis was used to identify predictive factors for mortality after PICH. A Cox proportional hazards model was fitted to identify predictive factors for recurrent ICH or stroke. A total of 746 charts were identified by computer search. After abstraction, 423 index patients with PICH were identified. Of these, 27.4% died in the first 30 days of their admission. Predictors of death were age, intraventricular rupture of hemorrhage, and trilobar hemorrhage. The recurrence rate for PICH was 2.4% (95% CI 1.4% to 3. 9%) per year, whereas the recurrence rate for ischemic cerebrovascular disease was 3.0% (95% CI 1.8% to 4.7%) per year. The only significant predictor of readmission for ICH was lobar location of the index hemorrhage, with a hazard ratio of 3.8 (95% CI 1.2 to 12.0). PICH has a high 30-day mortality rate. Survival from the initial insult portends a moderate risk of recurrence of 2. 4% per year for PICH and 3.0% per year for ischemic cerebrovascular disease. Patients with PICH are at risk for both ischemic stroke or TIA and recurrent hemorrhage; thus, PICH may be a marker for ischemic stroke. Patients with lobar hemorrhage have a 3.8-fold increased risk of recurrent ICH.

Recurrence of bleeding in patients with primary intracerebral hemorrhage.

Rebleeding in patients with primary intracerebral hemorrhage is considered uncommon, but there are no precise data to support this opinion. The purpose of this study was to assess the incidence and predictors of recurrent bleeding in survivors of primary intracerebral hemorrhage. As part of a prospective study, 112 survivors of a first primary intracerebral hemorrhage were followed up for a mean period of 84.1 months after their discharge. To ascertain risk factors that may influence rebleeding, several demographic, medical history, clinical, and laboratory variables were collected and analyzed. Twenty-four percent (27/112) of survivors experienced one or more rebleeding during the follow-up period, in 8 cases (30%) in the first year of follow-up; in the others recurrence occurred later, up to 11.5 years. Rebleeding had a high mortality rate: 70% of patients died as a consequence of their second or third hemorrhage. Univariate and multivariate analyses showed that lobar location of the first hemorrhage was the only significant predictor of rebleeding. Patients with rebleeding were more frequently older, more often had a history of previous transient ischemic attack or ischemic stroke, and less often had hyperlipidemia than patients without rebleeding, although these correlations did not reach statistical significance. During follow-up, poor control of arterial hypertension was found in 7% of hypertensive patients without rebleeding and in 47% of hypertensive patients with rebleeding. Our study showed that rebleeding after a first primary intracerebral hemorrhage is not as uncommon as is usually believed. The risk of rebleeding seems to be particularly high after hemorrhage at the junction of the gray and white matter, a site regarded as typical of hemorrhages due to amyloid angiopathy, and when arterial hypertension is poorly controlled.