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Background: Population-based studies have estimated that about 15% of ischemic strokes are caused by large-vessel cerebrovascular disease. We determined the types of large-vessel atherosclerosis responsible for ischemic strokes in a population-based stroke study. Methods: Patients with first-ever or recurrent ischemic stroke in the Greater Cincinnati area were identified during 2005 at all local hospitals. Study physicians assigned ischemic stroke subtypes. Overall event rates and incidence rates for first-ever events were calculated, and age-, race- and sex-adjusted to the 2000 US population. Results: There were 2,204 ischemic strokes, including 365 strokes of large-vessel subtype (16.6% of all ischemic strokes). Extracranial internal carotid artery (ICA) stenosis was associated with 8.0% of all ischemic strokes, while extracranial ICA occlusion and intracranial atherosclerosis were each associated with 3.5% of strokes. The annual rate of first-ever and recurrent stroke attributed to extracranial ICA was 13.4 (11.4–15.4) per 100,000 persons. We conservatively estimate that about 41,000 strokes may be attributed to extracranial ICA stenosis annually in the United States. Conclusions: Large-vessel atherosclerosis is an important cause of stroke, with extracranial ICA stenosis being significantly more common than extracranial ICA occlusion or intracranial atherosclerotic disease.

Background Spasticity often leads to symptomatic and functional problems that can cause disability for stroke survivors. We studied whether spasticity has a negative impact on health-related quality of life (HRQoL). Methods As part of the Greater Cincinnati/Northern Kentucky Stroke Study (NCT00642213), 460 ischemic stroke patients were interviewed during hospitalization and then followed over time. HRQoL was measured by the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores of the Short Form-12 (SF-12), EuroQol-5 dimension (EQ-5D), and Stroke-Specific Quality of Life (SSQOL) instruments, with lower scores indicating worse health. HRQoL differences between stroke survivors with and without spasticity were compared, adjusting for age, race, stroke severity, pre-stroke function, and comorbidities. Results Of the 460 ischemic stroke patients, 328 had spasticity data available 3 months after their stroke (mean age of 66 years, 49 % were female, and 26 % were black). Of these patients, 54 (16 %) reported having spasticity. Three months following their stroke, patients who reported spasticity had lower mean scores on the PCS (29.6 ± 1.4 vs 37.3 ± 0.6; P  < .001), EQ-5D (0.59 ± 0.03 vs 0.71 ± 0.01; P  < .001), and SSQOL (3.57 ± 0.08 versus 3.78 ± 0.03; P  = .03) compared with patients who did not report spasticity. Lower HRQoL scores were also observed at the 1-year (PCS, EQ-5D, and SSQOL) and 2-year (EQ-5D and SSQOL) interviews in those with spasticity compared with those without spasticity. Conclusions Statistically and clinically meaningful differences in HRQoL exist between stroke survivors with and without spasticity.

BackgroundThe REpeated ASSEssment of SurvivorS (REASSESS) study will conduct long-term cognitive, functional and neuropsychiatric performance assessments to determine whether evacuation of spontaneous intracerebral haemorrhage (ICH) reduces the risk of later cognitive decline in the ageing brain.Methods and analysisThis study will compare rates of cognitive decline under two treatment strategies for ICH. The first strategy is the use of minimally invasive surgery (MIS) with similar techniques as performed in (1) the Minimally Invasive Surgery plus rt-PA in the Treatment of Intracerebral haemorrhage Evacuation phase III (MISTIE III) trial, (2) the Early MiNimally-invasive Removal of IntraCerebral Haemorrhage (ENRICH) trial and (3) a single-centre cohort of consecutively treated patients with MIS. The second strategy is the current non-surgical standard of care using data from controls in MISTIE III and ENRICH and comparative data from The Ethnic/Racial Variations of ICH (ERICH) studyextended into the ERICH-Longitudinal study, which followed over 900 of ERICH cases with serial cognitive examinations. If successful, the REASSESS study could demonstrate that reduction of ICH volume is a critical target to reduce the risk of progressive cognitive decline, establish targets for residual haematoma volume reduction and determine if greater residual haematoma volume leads to a long-term inflammatory state.Ethics and disseminationApproval of this study was obtained from the Johns Hopkins University Institutional Review Board (IRB00311985). The findings of the study will be published in academic peer-reviewed journals.Trial registration number NCT05611918; ClinicalTrials.gov; registered on 23 May 2023.

1) To develop a machine learning approach for detecting stroke cases and subtypes from hospitalization data, 2) to assess algorithm performance and predictors on real-world data collected by a large-scale epidemiology study in the US; and 3) to identify directions for future development of high-precision stroke phenotypic signatures. We utilized 8,131 hospitalization events (ICD-9 codes 430-438) collected from the Greater Cincinnati/Northern Kentucky Stroke Study in 2005 and 2010. Detailed information from patients' medical records was abstracted for each event by trained research nurses. By analyzing the broad list of demographic and clinical variables, the machine learning algorithms predicted whether an event was a stroke case and, if so, the stroke subtype. The performance was validated on gold-standard labels adjudicated by stroke physicians, and results were compared with stroke classifications based on ICD-9 discharge codes, as well as labels determined by study nurses. The best performing machine learning algorithm achieved a performance of 88.57%/93.81%/92.80%/93.30%/89.84%/98.01% (accuracy/precision/recall/F-measure/area under ROC curve/area under precision-recall curve) on stroke case detection. For detecting stroke subtypes, the algorithm yielded an overall accuracy of 87.39% and greater than 85% precision on individual subtypes. The machine learning algorithms significantly outperformed the ICD-9 method on all measures (P value<0.001). Their performance was comparable to that of study nurses, with better tradeoff between precision and recall. The feature selection uncovered a subset of predictive variables that could facilitate future development of effective stroke phenotyping algorithms. By analyzing a broad array of patient data, the machine learning technologies held promise for improving detection of stroke diagnosis, thus unlocking high statistical power for subsequent genetic and genomic studies.

Appropriate thromboprophylaxis for patients with atrial fibrillation (AF) remains a national challenge. We hypothesized that provision of decision support in the form of an Atrial Fibrillation Decision Support Tool (AFDST) would improve thromboprophylaxis for AF patients. We conducted a cluster randomized trial involving 15 primary care practices and 1,493 adults with nonvalvular AF in an integrated health care system between April 2014 and February 2015. Physicians in the intervention group received patient-level treatment recommendations made by the AFDST. Our primary outcome was the proportion of patients with antithrombotic therapy that was discordant from AFDST recommendation. Treatment was discordant in 42% of 801 patients in the intervention group. Physicians reviewed reports for 240 patients. Among these patients, thromboprophylaxis was discordant in 63%, decreasing to 59% 1 year later (P = .02). In nonstratified analyses, changes in discordant care were not significantly different between the intervention group and control groups. In multivariate regression models, assignment to the intervention group resulted in a nonsignificant trend toward decreased discordance (P = .29), and being a patient of a resident physician (P = .02) and a higher HAS-BLED score predicted decreased discordance (P = .03), whereas female gender (P = .01) and a higher CHADSVASc score (P = .10) predicted increased discordance. Among patients whose physicians reviewed recommendations of the decision support tool discordant therapy decreased significantly over 1 year. However, in nonstratified analyses, the intervention did not result in significant improvements in discordant antithrombotic therapy.

BackgroundThe prognostic significance of the affected hemisphere in haemorrhagic stroke remains uncertain. We aimed to determine the relationship between the affected hemisphere (right or left) and differences in non-motor outcomes, including mood and pain, in patients with acute, supratentorial intracerebral haemorrhage (ICH). These non-motor outcomes are often overlooked in studies following ICH but impact patient recovery and well-being.MethodsA secondary prespecified analysis of the Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation (MISTIE) III study—a randomised, international, multicentre, placebo-controlled trial of participants with spontaneous, non-traumatic, supratentorial ICH of 30 mL or more that evaluated minimally invasive surgery with thrombolysis compared with standard medical care. Outcomes included EQ-5D three-level version (EQ-5D-3L, composite and individual non-motor components) and modified Rankin scale (mRS) scores at days 30, 180 and 365 post-ICH.ResultsA total of 493 participants were eligible for analysis at day 30 following ICH. In multivariable analyses, patients with right hemispheric ICH were more likely to report problems with pain and discomfort at days 30 (β=0.257 (95% CI 0.131, 0.383)), 180 (β=0.213 (95% CI 0.090, 0.336)) and 365 (β=0.209 (95% CI 0.090, 0.328)) post-ICH. Patients with right hemispheric ICH were also more likely to report problems with anxiety and depression at days 30 (β=0.160 (95% CI 0.030, 0.291)) and 180 (β=0.171 (95% CI 0.049, 0.293)) following ICH. There were no differences in mRS scores between patients with left or right-sided haemorrhages.ConclusionsRight hemispheric lesions were associated with increased reports of mood-related symptoms (depression, anxiety) and pain in patients with acute ICH over time.Trial registration number NCT01827046.

IntroductionCurrent guidelines recommend blood pressure (BP) lowering in patients after acute intracerebral haemorrhage (ICH) without guidance on initial choice of antihypertensive class. This study sought to determine if initial antihypertensive class differentially effects acute BP lowering in a large multiethnic ICH cohort.MethodsSubjects enrolled in the Ethnic/Racial Variations in ICH study between August 2010 and August 2017 with elevated admission BP and who received labetalol, nicardipine or hydralazine monotherapy as initial antihypertensive were analysed. Primary outcomes were systolic and diastolic BP changes from baseline to first BP measurement after initial antihypertensive treatment. Secondary outcomes included haematoma expansion (HE), hospital length of stay (LOS) and modified Rankin Score (mRS) up to 12 months after ICH. Exploratory outcomes assessed effects of race/ethnicity. Linear and logistic regression analyses, adjusted for relevant covariates, were performed to determine associations of antihypertensive class with outcomes.ResultsIn total, 1156 cases were used in analyses. Antihypertensive class was associated with diastolic BP change (p=0.003), but not systolic BP change (p=0.419). Initial dosing with nicardipine lowered acute diastolic BP than labetalol (least square mean difference (labetalol-nicardipine)=5.47 (2.37, 8.57), p<0.001). Initial antihypertensive class was also found to be associated with LOS (p=0.028), but not with HE (p=0.406), mortality (p=0.118), discharge disposition (p=0.083) or mRS score at discharge, 3, 6 and 12 months follow-up (p=0.262, 0.276, 0.152 and 0.36, respectively). Race/ethnicity variably affected multivariable models.ConclusionIn this large acute ICH cohort, initial antihypertensive class was associated with acute diastolic, but not systolic, BP-lowering suggesting differential effects of antihypertensive agents.Trial registration number NCT01202864.

Background and purposePatients with stroke can experience neurological deterioration in the prehospital setting. We evaluated patients with stroke to determine factors associated with prehospital neurological deterioration (PND).MethodsAmong the Greater Cincinnati/Northern Kentucky region (population ~1.3 million), we screened all 15 local hospitals’ admissions from 2010 for acute stroke and included patients aged ≥20. The GCS was compared between emergency medical services (EMS) arrival and hospital arrival, with decrease ≥2 points considered PND. Data obtained retrospectively included demographics, medical history and medication use, stroke subtype (eg, ischaemic stroke (IS), intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH)) and IS subtype (eg, small vessel, large vessel, cardioembolic), seizure at onset, time intervals between symptom onset, EMS arrival and hospital arrival, EMS level of training, and blood pressure and serum glucose on EMS arrival.ResultsOf 2708 total patients who had a stroke, 1092 patients (median (IQR) age 74 (61–83) years; 56% women; 21% black) were analysed. PND occurred in 129 cases (12%), including 9% of IS, 24% of ICH and 16% of SAH. In multivariable analysis, black race, atrial fibrillation, haemorrhagic subtype and ALS level of transport were associated with PND.ConclusionHaemorrhage and atrial fibrillation is associated with PND in stroke, and further investigation is needed to establish whether PND can be predicted. Further studies are also needed to assess whether preferential transport of patients with deterioration to hospitals equipped with higher levels of care is beneficial, identify why race is associated with deterioration and to test therapies targeting PND.

Many studies show that a major barrier to short-term treatment of stroke is patient or bystander delay in responding to stroke symptoms. Most studies have found that less than half of stroke/transient ischemic attack (TIA) events result in a 911 call. We sought to determine which symptoms prompt the public to call 911. A population of 1.3 million within a 5-county region was screened for TIA and all strokes in 1999 using all local hospital International Classification of Diseases, Ninth Edition, codes for stroke (430-436) during 1999. Documented stroke symptoms were abstracted from the medical record. Symptoms were grouped as weakness, numbness, speech/language, confusion/decreased level of consciousness, headache, visual changes, and dizziness/vertigo/coordination. Cases included in this analysis had their strokes at home or work and presented to an emergency department. Logistic regression assessed which symptoms predicted a 911 call, adjusting for age, race, sex, prior stroke, baseline disability, overall stroke severity, home vs work, and stroke subtype. Two thousand nine hundred seventy-five stroke/TIA patients met inclusion criteria, of whom 40% used emergency medical services. After adjustment, symptoms that increased odds of a 911 call were weakness, confusion/decreased level of consciousness, speech/language, and dizziness/coordination/vertigo. Numbness was less likely to result in a 911 call as were visual changes. The presence of headache was not associated with the decision to call 911. The public appears to respond differently based on the type of stroke symptom, independent of overall severity. Public awareness messages regarding stroke warning signs should be designed with this in mind.

Background and Purpose: Very few cases of intracranial aneurysms (IAs) in twins have been reported. Previous work has suggested that vulnerability to IA formation is heritable. Twin studies provide an opportunity to evaluate the impact of genetics on IA characteristics, including IA location. We therefore sought to examine IA location concordance, multiplicity, and rupture status within affected twin-pairs. Methods: The Familial Intracranial Aneurysm study was a multicenter study whose goal was to identify genetic and other risk factors for formation and rupture of IAs. The study required at least three affected family members or an affected sibling pair for inclusion. Subjects with fusiform aneurysms, an IA associated with an AVM, or a family history of conditions known to predispose to IA formation, such as polycystic kidney disease, Ehlers-Danlos syndrome, Marfan syndrome, fibromuscular dysplasia, or moyamoya syndrome were excluded. Twin-pairs were identified by birth date and were classified as monozygotic (MZ) or dizygotic (DZ) through DNA marker genotypes. In addition to zygosity, we evaluated twin-pairs by smoking status, major arterial territory of IAs, and rupture status. Location concordance was defined as the presence of an IA in the same arterial distribution (ICA, MCA, ACA, and vertebrobasilar), irrespective of laterality, in both members of a twin-pair. The Fisher exact test was used for comparisons between MZ and DZ twin-pairs. Results: A total of 16 affected twin-pairs were identified. Location concordance was observed in 8 of 11 MZ twin-pairs but in only 1 of 5 DZ twin-pairs (p = 0.08). Three MZ subjects had unknown IA locations and comprised the three instances of MZ discordance. Six of the 11 MZ twin-pairs and none of the 5 DZ twin-pairs had IAs in the ICA distribution (p = 0.03). Multiple IAs were observed in 11 of 22 MZ and 5 of 10 DZ twin-pairs. Thirteen (13) of the 32 subjects had an IA rupture, including 10 of 22 MZ twins. Conclusions: We found that arterial location concordance was greater in MZ than DZ twins, which suggests a genetic influence upon aneurysm location. The 16 twin-pairs in the present study are nearly the total of affected twin-pairs that have been reported in the literature to date. Further studies are needed to determine the impact of genetics in the formation and rupture of IAs.