Search

Most traumatic brain injuries (TBIs) are classified as mild (mTBI) based on admission Glasgow Coma Scale (GCS) scores of 13 to 15. The prevalence of persistent functional limitations for these patients is unclear.To characterize the natural history of recovery of daily function following mTBI vs peripheral orthopedic traumatic injury in the first 12 months postinjury using data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, and, using clinical computed tomographic (CT) scans, examine whether the presence (CT+) or absence (CT-) of acute intracranial findings in the mTBI group was associated with outcomes.TRACK-TBI, a cohort study of patients with mTBI presenting to US level I trauma centers, enrolled patients from February 26, 2014, to August 8, 2018, and followed up for 12 months. A total of 1453 patients at 11 level I trauma center emergency departments or inpatient units met inclusion criteria (ie, mTBI [n = 1154] or peripheral orthopedic traumatic injury [n = 299]) and were enrolled within 24 hours of injury; mTBI participants had admission GCS scores of 13 to 15 and clinical head CT scans. Patients with peripheral orthopedic trauma injury served as the control (OTC) group.Participants with mTBI or OTC.The Glasgow Outcome Scale Extended (GOSE) scale score, reflecting injury-related functional limitations across broad life domains at 2 weeks and 3, 6, and 12 months postinjury was the primary outcome. The possible score range of the GOSE score is 1 (dead) to 8 (upper good recovery), with a score less than 8 indicating some degree of functional impairment.Of the 1453 participants, 953 (65.6%) were men; mean (SD) age was 40.9 (17.1) years in the mTBI group and 40.9 (15.4) years in the OTC group. Most participants (mTBI, 87%; OTC, 93%) reported functional limitations (GOSE8) at 2 weeks postinjury. At 12 months, the percentage of mTBI participants reporting functional limitations was 53% (95% CI, 49%-56%) vs 38% (95% CI, 30%-45%) for OTCs. A higher percentage of CT+ patients reported impairment (61%) compared with the mTBI CT- group (49%; relative risk [RR], 1.24; 95% CI, 1.08-1.43) and a higher percentage in the mTBI CT-group compared with the OTC group (RR, 1.28; 95% CI, 1.02-1.60).Most patients with mTBI presenting to US level I trauma centers report persistent, injury-related life difficulties at 1 year postinjury, suggesting the need for more systematic follow-up of patients with mTBI to provide treatments and reduce the risk of chronic problems after mTBI.

Importance The etiology and significance of diffusion-weighted imaging (DWI) lesions in patients with acute intracerebral hemorrhage (ICH) remain unclear. Objective To evaluate which factors are associated with DWI lesions, whether associated factors differ by ICH location, and whether DWI lesions are associated with functional outcomes. Design, Setting, and Participants This analysis pooled individual patient data from 3 randomized clinical trials (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3 trial, Antihypertensive Treatment of Acute Cerebral Hemorrhage trial, and Intracerebral Hemorrhage Deferoxamine phase 2 trial) and 1 multicenter prospective study (Ethnic/Racial Variations of Intracerebral Hemorrhage). Patients were enrolled from August 1, 2010, to September 30, 2018. Of the 4782 patients, 1788 who underwent magnetic resonance imaging scans of the brain were included. Data were analyzed from July 1 to December 31, 2019. Main Outcomes and Measures The primary outcome consisted of factors associated with DWI lesions. Secondary outcomes were poor functional outcome, defined as a modified Rankin score (mRS) of 4 to 6, and mortality, both assessed at 3 months. Mixed-effects logistic regression was used to evaluate the association between exposures and outcomes. Subgroup analyses stratified by hematoma location were performed. Results After exclusion of 36 patients with missing data on DWI lesions, 1752 patients were included in the analysis (1019 men [58.2%]; mean [SD] age, 60.8 [13.3] years). Diffusion-weighted imaging lesions occurred in 549 patients (31.3%). In mixed-effects regression models, factors associated with DWI lesions included younger age (odds ratio [OR] per year, 0.98; 95% CI, 0.97-0.99), black race (OR, 1.64; 95% CI, 1.17-2.30), admission systolic blood pressure (OR per 10–mm Hg increase, 1.13; 95% CI, 1.08-1.18), baseline hematoma volume (OR per 10-mL increase, 1.12; 95% CI, 1.02-1.22), cerebral microbleeds (OR, 1.85; 95% CI, 1.39-2.46), and leukoaraiosis (OR, 1.59; 95% CI, 1.67-2.17). Diffusion-weighted imaging lesions were independently associated with poor mRS (OR, 1.50; 95% CI, 1.13-2.00), but not with mortality (OR, 1.11; 95% CI, 0.72-1.71). In subgroup analyses, similar factors were associated with DWI lesions in lobar and deep ICH. Diffusion-weighted imaging lesions were associated with poor mRS in deep but not lobar ICH. Conclusions and Relevance In a large, heterogeneous cohort of prospectively identified patients with ICH, results were consistent with the hypothesis that DWI lesions represent acute sequelae of chronic cerebral small vessel disease, particularly hypertensive vasculopathy. Diffusion-weighted imaging lesions portend a worse prognosis after ICH, mainly deep hemorrhages.

IMPORTANCE The ability of present-day etiologic stroke classification systems to generate subtypes with discrete stroke characteristics is not known. OBJECTIVE To test the hypothesis that etiologic stroke subtyping identifies different disease processes that can be recognized through their different clinical courses. DESIGN, SETTING, AND PARTICIPANTS We performed a head-to-head evaluation of the ability of the Causative Classification of Stroke (CCS), Trial of Org 10172 in Acute Stroke Treatment (TOAST), and ASCO (A for atherosclerosis, S for small-vessel disease, C for cardiac source, and O for other cause) classification systems to generate etiologic subtypes with different clinical, imaging, and prognostic characteristics in 1816 patients with ischemic stroke. This study included 2 cohorts recruited at separate periods; the first cohort was recruited between April 2003 and June 2006 and the second between June 2009 and December 2011. Data analysis was performed between June 2014 and May 2016. MAIN OUTCOMES AND MEASURES Separate teams of stroke-trained neurologists performed CCS, TOAST, and ASCO classifications based on information available at the time of hospital discharge. We assessed the association between etiologic subtypes and stroke characteristics by computing receiver operating characteristic curves for binary variables (90-day stroke recurrence and 90-day mortality) and by calculating the ratio of between-category to within-category variability from the analysis of variance for continuous variables (admission National Institutes of Health Stroke Scale score and acute infarct volume). RESULTS Among the 1816 patients included, the median age was 70 years (interquartile range, 58-80 years) (830 women [46%]). The classification systems differed in their ability to assign stroke etiologies into known subtypes; the size of the undetermined category was 33% by CCS, 53% by TOAST, and 42% by ASCO (P < .001 for all binary comparisons). All systems provided significant discrimination for the validation variables tested. For the primary validation variable (90-day recurrence), the area under the receiver operating characteristic curve was 0.71 (95% CI, 0.66-0.75) for CCS, 0.61 (95% CI, 0.56-0.67) for TOAST, and 0.66 (95% CI, 0.60-0.71) for ASCO (P = .01 for CCS vs ASCO; P < .001 for CCS vs TOAST; P = .13 for ASCO vs TOAST). The classification systems exhibited similar discrimination for 90-day mortality. For admission National Institutes of Health Stroke Scale score and acute infarct volume, CCS generated more distinct subtypes with higher between-category to within-category variability than TOAST and ASCO. CONCLUSIONS AND RELEVANCE Our findings suggest that the major etiologic stroke subtypes are distinct categories with different stroke characteristics irrespective of the classification system used to identify them. We further show that CCS generates discrete etiologic categories with more diverse clinical, imaging, and prognostic characteristics than either TOAST or ASCO.

Importance Response to intensive blood pressure (BP) lowering in acute intracerebral hemorrhage (ICH) might vary with the degree of underlying cerebral small vessel disease. Objectives To characterize cerebral microbleeds (CMBs) in acute ICH and to assess the potential for interaction between underlying small vessel disease (as indicated by CMB number and location) and assignment to acute intensive BP targeting for functional outcomes and hematoma expansion. Design, Setting, and Participants Preplanned subgroup analyses in the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial were performed. The ATACH-2 was an open-label international randomized clinical trial that investigated optimal acute BP lowering in 1000 patients with acute ICH. Analyses followed the intent-to-treat paradigm. Participants were enrolled between May 2011 and September 2015 and followed up for 3 months. Eligible participants were aged at least 18 years with ICH volumes less than 60 mL on computed tomography (CT) and a Glasgow Coma Scale score of at least 5 on initial assessment, in whom study drug could be initiated within 4.5 hours of symptom onset. Eight hundred thirty-three participants were excluded, leaving 167 who had an interpretable axial T2*-weighted gradient-recalled echo sequence on magnetic resonance imaging to assess CMBs for inclusion in these subgroup analyses. Main Outcomes and Measures The primary outcome of interest was death or disability (modified Ranking Scale score, 4-6) at 3 months. The secondary outcome of interest was hematoma volume expansion of at least 33% on a CT scan obtained 24 hours after randomization compared with the entry scan. Results A total of 167 patients were included; their mean (SD) age was 61.9 (13.2) years, and 98 (58.7%) were male. Cerebral microbleeds were present in 120 patients. Forty-six of 157 (29.3%) patients had poor outcome (modified Ranking Scale score, ≥4), and hematoma expansion was observed in 29 of 144 (20.1%) patients. Risk of poor outcome was similar for those assigned to intensive vs standard acute BP lowering among patients with CMBs (relative risk, 1.19; 95% CI, 0.61-2.33;P = .61) and those without CMBs (relative risk, 1.42; 95% CI, 0.43-4.70;P = .57), and no significant interaction was observed (interaction coefficient, 0.18; 95% CI, −1.20 to 1.55;P = .80). Risk of hematoma expansion was also similar, and no significant interaction between treatment and CMBs was observed (interaction coefficient, 0.62; 95% CI, −1.08 to 2.31;P = .48). Conclusions and Relevance Cerebral microbleeds are highly prevalent among patients with ICH but do not seem to influence response to acute intensive BP treatment. Trial Registration ClinicalTrials.gov Identifier:NCT01176565

The computed tomographic angiography (CTA) spot sign is associated with intracerebral hemorrhage (ICH) expansion and may mark those patients most likely to benefit from intensive blood pressure (BP) reduction.To investigate whether the spot sign is associated with ICH expansion across a wide range of centers and whether intensive BP reduction decreases hematoma expansion and improves outcome in patients with ICH and a spot sign.SCORE-IT (Spot Sign Score in Restricting ICH Growth) is a preplanned prospective observational study nested in the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-II) randomized clinical trial. Participants included consecutive patients with primary ICH who underwent a CTA within 8 hours from onset at 59 sites from May 15, 2011, through December 19, 2015. Data were analyzed for the present study from July 1 to August 31, 2016.Patients in ATACH-II were randomized to intensive (systolic BP target,140 mm Hg) vs standard (systolic BP target,180 mm Hg) BP reduction within 4.5 hours from onset. Expansion of ICH was defined as hematoma growth of greater than 33%, and an unfavorable outcome was defined as a 90-day modified Rankin Scale score of 4 or greater (range, 0-6). The association among BP reduction, ICH expansion, and outcome was investigated with multivariable logistic regression.A total of 133 patients (83 men [62.4%] and 50 women [37.6%]; mean [SD] age, 61.9 [13.1] years) were included. Of these, 53 (39.8%) had a spot sign, and 24 of 123 without missing data (19.5%) experienced ICH expansion. The spot sign was associated with expansion with sensitivity of 0.54 (95% CI, 0.34-0.74) and specificity of 0.63 (95% CI, 0.53-0.72). After adjustment for potential confounders, intensive BP treatment was not associated with a significant reduction of ICH expansion (relative risk, 0.83; 95% CI, 0.27-2.51; P = .74) or improved outcome (relative risk of 90-day modified Rankin Scale score ≥4, 1.24; 95% CI, 0.53-2.91; P = .62) in spot sign-positive patients.The predictive performance of the spot sign for ICH expansion was lower than in prior reports from single-center studies. No evidence suggested that patients with ICH and a spot sign specifically benefit from intensive BP reduction.clinicaltrials.gov Identifier: NCT01176565.

Importance Hematoma expansion is an important determinant of outcome in spontaneous intracerebral hemorrhage (ICH) due to small vessel disease (SVD), but the association between the severity of the underlying SVD and the extent of bleeding at the acute phase is unknown to date. Objective To investigate the association between key magnetic resonance imaging (MRI) markers of SVD (as per the Standards for Reporting Vascular Changes on Neuroimaging [STRIVE] guidelines) and hematoma volume and expansion in patients with lobar or deep ICH. Design, Setting, and Participants Analysis of data collected from 418 consecutive patients admitted with primary lobar or deep ICH to a single tertiary care medical center between January 1, 2000, and October 1, 2012. Data were analyzed on March 4, 2016. Participants were consecutive patients with computed tomographic images allowing ICH volume calculation and MRI allowing imaging markers of SVD assessment. Main Outcomes and Measures The ICH volumes at baseline and within 48 hours after symptom onset were measured in 418 patients with spontaneous ICH without anticoagulant therapy, and hematoma expansion was calculated. Cerebral microbleeds, cortical superficial siderosis, and white matter hyperintensity volume were assessed on MRI. The associations between these SVD markers and ICH volume, as well as hematoma expansion, were investigated using multivariable models. Results This study analyzed 254 patients with lobar ICH (mean [SD] age, 75 [11] years and 140 [55.1%] female) and 164 patients with deep ICH (mean [SD] age 67 [14] years and 71 [43.3%] female). The presence of cortical superficial siderosis was an independent variable associated with larger ICH volume in the lobar ICH group (odds ratio per quintile increase in final ICH volume, 1.49; 95% CI, 1.14-1.94; P = .004). In multivariable models, the absence of cerebral microbleeds was associated with larger ICH volume for both the lobar and deep ICH groups (odds ratios per quintile increase in final ICH volume, 1.41; 95% CI, 1.11-1.81; P = .006 and 1.43; 95% CI, 1.04-1.99; P = .03; respectively) and with hematoma expansion in the lobar ICH group (odds ratio, 1.70; 95% CI, 1.07-2.92; P = .04). The white matter hyperintensity volumes were not associated with either hematoma volume or expansion. Conclusions and Relevance In patients admitted with primary lobar or deep ICH to a single tertiary care medical center, the presence of cortical superficial siderosis was an independent variable associated with larger lobar ICH volume, and the absence of cerebral microbleeds was associated with larger lobar and deep ICHs. The absence of cerebral microbleeds was independently associated with more frequent hematoma expansion in patients with lobar ICH. We provide an analytical framework for future studies aimed at limiting hematoma expansion.

Importance Calcium is a key cofactor of the coagulation cascade and may play a role in the pathophysiology of intracerebral hemorrhage (ICH). Objective To investigate whether a low serum calcium level is associated with an increase in the extent of bleeding in patients with ICH as measured by baseline hematoma volume and risk of hematoma expansion. Design, Setting, and Participants Prospective cohort study of 2103 consecutive patients with primary ICH ascertained during the period between 1994 and 2015 at an academic medical center. The statistical analysis was performed in January 2016. Main Outcomes and Measures Total calcium level was measured on admission, and hypocalcemia was defined as a serum calcium level of less than 8.4 mg/dL. Baseline and follow-up hematoma volumes, detected by noncontrast computed tomography, were measured using a computer-assisted semiautomatic analysis. Hematoma expansion was defined as an increase of more than 30% or 6 mL from baseline ICH volume. Associations between serum calcium level and baseline hematoma volume and between serum calcium level and ICH expansion were investigated in multivariable linear and logistic regression models, respectively. Results A total of 2123 patients with primary ICH were screened, and 2103 patients met the inclusion criteria (mean [SD] age, 72.7 [12.5] years; 54.3% male patients), of whom 229 (10.9%) had hypocalcemia on admission. Hypocalcemic patients had a higher median baseline hematoma volume than did normocalcemic patients (37 mL [IQR, 15-72 mL] vs 16 mL [IQR, 6-44 mL]; P P P = .01), after adjusting for other confounders. Conclusions and Relevance Hypocalcemia correlates with the extent of bleeding in patients with ICH. A low calcium level may be associated with a subtle coagulopathy predisposing to increased bleeding and might therefore be a promising therapeutic target for acute ICH treatment trials.

Patients who have experienced intracerebral hemorrhage (ICH) appear to develop cognitive impairment at high rates, both early after ICH and over the long term.To identify and compare risk factors for early and delayed dementia after ICH.A longitudinal study enrolled patients who had experienced ICH from January 1, 2006, to December 31, 2013. A total of 738 participants 18 years or older, without pre-ICH dementia, who presented to a tertiary care academic institution with primary ICH were included in the analyses of early post-ICH dementia (EPID). After accounting for incident dementia and mortality at 6 months, 435 participants were included in the analyses of delayed post-ICH dementia (DPID).Intracerebral hemorrhage.Cognitive performance was captured using the modified Telephone Interview for Cognitive Status test. Outcomes included EPID, diagnosed within 6 months after ICH, and DPID, diagnosed beyond 6 months after ICH.Among 738 patients who had experienced ICH (mean [SD] age, 74.3 [12.1] years; 384 men [52.0%]), 140 (19.0%) developed dementia within 6 months. A total of 435 patients without dementia at 6 months were followed up longitudinally (median follow-up, 47.4 months; interquartile range, 43.4-52.1 months), with an estimated yearly incidence of dementia of 5.8% (95% CI, 5.1%-7.0%). Larger hematoma size (hazard ratio [HR], 1.47 per 10-mL increase; 95% CI, 1.09-1.97; P .001 for heterogeneity) and lobar location of ICH (HR, 2.04; 95% CI, 1.06-3.91; P = .02 for heterogeneity) were associated with EPID but not with DPID. Educational level (HR, 0.60; 95% CI, 0.40-0.89; P .001 for heterogeneity), incident mood symptoms (HR, 1.29; 95% CI, 1.02-1.63; P = .01 for heterogeneity), and white matter disease as defined via computed tomography (HR, 1.70; 95% CI, 1.07-2.71; P = .04 for heterogeneity) were associated with DPID but not EPID.Incident dementia early after ICH is strongly associated with hematoma size and location. Delayed incident dementia is frequent among patients who have experienced ICH and is not prominently associated with acute characteristics of ICH. These findings suggest the existence of heterogeneous biological mechanisms accounting for early vs delayed cognitive decline among patients who have experienced ICH.

Many clinical trials focus on restricting hematoma expansion following acute intracerebral hemorrhage (ICH), but selecting those patients at highest risk of hematoma expansion is challenging.To develop a prediction score for hematoma expansion in patients with primary ICH.Prospective cohort study at 2 urban academic medical centers among patients having primary ICH with available baseline and follow-up computed tomography for volumetric analysis (817 patients in the development cohort and 195 patients in the independent validation cohort).Hematoma expansion was assessed using semiautomated software and was defined as more than 6 mL or 33% growth. Covariates were tested for association with hematoma expansion using univariate and multivariable logistic regression. A 9-point prediction score was derived based on the regression estimates and was subsequently tested in the independent validation cohort.Hematoma expansion occurred in 156 patients (19.1%). In multivariable analysis, predictors of expansion were as follows: warfarin sodium use, the computed tomography angiography spot sign, and shorter time to computed tomography (≤ 6 vs6 hours) (P .001 for all), as well as baseline ICH volume (30 [reference], 30-60 [P = .03], and60 [P = .005] mL). The incidence of hematoma expansion steadily increased with higher scores. In the independent validation cohort (n = 195), our prediction score performed well and showed strong association with hematoma expansion (odds ratio, 4.59; P .001 for a high vs low score). The C statistics for the score were 0.72 for the development cohort and 0.77 for the independent validation cohort.A 9-point prediction score for hematoma expansion was developed and independently validated. The results open a path for individualized treatment and trial design in ICH aimed at patients at highest risk of hematoma expansion with maximum potential for therapeutic benefit.