Objective:We sought to determine whether MRI-based Cerebral Small Vessel Disease (CSVD) burden assessment, in addition to clinical and CT data, improved prediction of cognitive impairment after spontaneous Intracerebral Hemorrhage (ICH).Methods:We analyzed data from ICH survivors enrolled in a single-center prospective study. We employed three validated CSVD burden scores: global, cerebral amyloid angiopathy (CAA)-specific, hypertensive arteriopathy (HTNA)-specific. We quantified cognitive performance by administering the modified Telephone Interview for Cognitive Status (TICS-m) test. We utilized linear mixed models to model cognitive decline rates, and survival models for new-onset dementia. We calculated CSVD scores’ cut-offs to maximize predictive performance for dementia diagnosis.Results:We enrolled 612 ICH survivors, and followed them for a median of 46.3 months (Inter-Quartile Range: 35.5-58.7). A total of 214/612 (35%) participants developed dementia. Higher global CSVD scores at baseline were associated with faster cognitive decline (Coeff -0.25, Standard Error [SE] 0.02) and dementia risk (Sub-Hazard Ratio 1.35, 95% CI 1.10-1.65). The global score outperformed the CAA and HTNA scores in predicting post-ICH dementia (all p<0.05). Compared to a model including readily available clinical and CT data, inclusion of the global CSVD score resulted in improved prediction of post-ICH dementia (Area Under the Curve [AUC] 0.89, SE 0.02 vs. AUC 0.81, SE 0.03, p = 0.008 for comparison). Global CSVD scores ≥ 2 had highest sensitivity (83%) and specificity (91%) for dementia diagnosis.Conclusions:A validated MRI-based CSVD score is associated with cognitive performance after ICH, and improved diagnostic accuracy for predicting new onset of dementia.
IMPORTANCESelective 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. OBJECTIVE To determine whether SSRI use among survivors of primary ICH was associated with ICH recurrence and decreased severity of depressive symptoms. DESIGN, SETTING, AND PARTICIPANTSLongitudinal 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. MAIN OUTCOMES AND MEASURESWe 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. RESULTSMean 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.CONCLUSIONS AND RELEVANCE 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.
Introduction: Survivors of Intracerebral Hemorrhage (ICH) are at high risk for cognitive impairment. Previous studies clarified that Cerebral Small Vessel Disease (CSVD) is a primary contributor to post-ICH dementia, but these observations have failed to transform clinical or research practice standards to date. We sought to determine whether a validated MRI CSVD scoring system could readily predict cognitive impairment after ICH. Methods: We analyzed data from ICH survivors with no history of prior cognitive impairment, enrolled in a single-center prospective study. We reviewed MRI scans to compute: 1) a validated 6-point score for CSVD burden based on presence of microbleeds, white matter hyperintensities, lacunes and >20 basal ganglia enlarged perivascular spaces; 2) cortical atrophy. We quantified cognitive performance by: 1) administering the Telephone Interview for Cognitive Status (TICS) test; 2) identifying diagnosis of dementia based on medical records. We utilized linear mixed model analyses to identify predictors of changes in TICS score, and Cox regression to identify predictors of new-onset dementia. We calculated CSVD score cut-offs to maximize sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for diagnosis of dementia. Results: We enrolled 612 primary ICH survivors, and followed them for a median of 46.3 months (Inter-Quartile Range: 35.5-58.7). A total of 214/612 (35%) participants developed dementia. Increasing CSVD scores were associated with faster cognitive decline (Coeff -0.25, Standard Error 0.02) and dementia diagnosis (Hazard Ratio 1.33, 95% CI 1.08-1.64). Age, increasing atrophy scale score, lower TICS score at baseline and systolic blood pressure were also independently associated with faster cognitive decline and new-onset dementia (all p<0.001). A CSVD score cut-off of ≥ 2 had highest sensitivity (83%) and specificity (91%) for dementia diagnosis, with PPV of 84% and NPV of 91% respectively. Conclusion: This validated CSVD score is strongly associated with cognitive performance after ICH, with excellent predictive performance for future diagnosis of dementia. Our results support its implementation in clinical care and in future studies of post-ICH dementia.
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.
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