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Background: A naturally occurring loss-of-function mutation in the gene for C-C chemokine receptor type 5 (CCR5-Δ32) has recently been reported as a protective factor in post-stroke motor and cognitive recovery. We sought to examine whether this mutation also prevented the development of depressive symptoms up to 2 years after a stroke. Methods: Participants were survivors of a first-ever mild to moderate ischemic stroke or transient ischemic attack from the TABASCO prospective study who underwent a 3 T MRI at baseline and were examined by a multiprofessional team 6, 12 and 24 months after the event, including an evaluation of depressive symptoms using the Geriatric Depression Scale. Results: CCR5-Δ32 status and a baseline depression evaluation were available for 435 patients. Compared with noncarriers, CCR5-Δ32 carriers (16.1%) had fewer depressive symptoms at admission (p = 0.035) and at 6 months (p < 0.001), 12 months (p < 0.001) and 24 months (p = 0.006) after the index event. This association remained significant at 6 and 12 months after adjustment for age, sex, education, antidepressant use, ethnicity and the presence of cortical infarcts. These findings were more robust in women. Compared to baseline, depressive symptoms in CCR5-Δ32 noncarriers tended to remain stable or grow worse over time, but in CCR5-Δ32 carriers, symptoms tended to improve. Limitations: A limitation of this study was the exclusion of patients who had a severe stroke or who had pre-stroke depression. Conclusion: Carriers of the CCR5-Δ32 allele had a lower tendency to develop depressive symptoms post-stroke, and this phenomenon was more prominent in women. These findings could have clinical implications; they suggest a mechanism-based treatment target for post-stroke depression. Drugs mimicking this loss-of-function mutation exist and could serve as a novel antidepressant therapy.

Background: Migraine is known to mildly increase the risk for ischemic stroke and is associated with vascular MRI markers. However, the potential effect of chronic headache (CH) on stroke outcomes has not been studied. Objective: We aimed to assess the interrelation between CH and post-stroke cognitive impairment. Methods: Data from 455 patients with a first ever stroke from the TABASCO study was available. All patients underwent 3T brain MRI, blood analysis, and a serial cognitive assessment at baseline and 6, 12, and 24 months after. Results: Eighty-five (18.7%) patients reported suffering from CH, of whom 53 (62.4%) reported symptoms of photophobia or nausea, and 34 (40%) reported an aura. CH was associated with female sex, lower prevalence of T2DM (p

Contains fulltext : 235277.pdf (Publisher’s version ) (Closed access) BACKGROUND: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. METHODS: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. FINDINGS: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. INTERPRETATION: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. FUNDING: British Heart Foundation and Stroke Association.

Introduction: The COVID-19 pandemic overwhelmed health-care systems worldwide, and medical care for other acute diseases was negatively impacted. We aimed to investigate the effect of the COVID-19 outbreak on admission rates and in-hospital care for acute stroke and transient ischemic attack (TIA) in Israel, shortly after the start of the pandemic. Methods: We conducted a retrospective observational study, based on data reported to the Israeli National Stroke Registry from 7 tertiary hospitals. All hospital admissions for acute stroke or TIA that occurred between January 1 and April 30, 2020 were included. Data were stratified into 2 periods according to the timing of COVID-19 restrictions as follows: (1) “pre-pandemic” – January 1 to March 7, 2020 and (2) “pandemic” – March 8 to April 30, 2020. We compared the weekly counts of hospitalizations between the 2 periods. We further investigated changes in demographic characteristics and in some key parameters of stroke care, including the percentage of reperfusion therapies performed, time from hospital arrival to brain imaging and to thrombolysis, length of hospital stay, and in-hospital mortality. Results: 2,260 cases were included: 1,469 in the pre-COVID-19 period and 791 in the COVID-19 period. Hospital admissions significantly declined between the 2 periods, by 48% for TIA (rate ratio [RR] = 0.52; 95% CI 0.43–0.64) and by 29% for stroke (RR = 0.71; 95% CI 0.64–0.78). No significant changes were detected in demographic characteristics and in most parameters of stroke management. While the percentage of reperfusion therapies performed remained unchanged, the absolute number of patients treated with reperfusion therapies seemed to decrease. Higher in-hospital mortality was observed only for hemorrhagic stroke. Conclusion: The marked decrease in admissions for acute stroke and TIA, occurring at a time of a relatively low burden of COVID-19, is of great concern. Public awareness campaigns are needed as patients reluctant to seek urgent stroke care are deprived of lifesaving procedures and secondary prevention treatments.

Background Susac syndrome (SuS) is a rare condition characterized by a clinical triad of sensorineural hearing loss, branch artery occlusion and encephalopathy. This study reports an increased incidence of SuS in Israel. We describe the clinical characteristics of these patients, diagnostic procedures and the use and subsequent outcomes of newly published treatment guidelines. Methods This is a single center retrospective study. Patients who were diagnosed with SuS between July 2017 and August 2018 were enrolled in this study. Results Seven patients were diagnosed with SuS according to the diagnostic criteria in a time period of 13 months. The annual incidence was recently evaluated in Austria to be 0.024/100000, therefore, our case series represent at least a 5.4- fold increase in the annual incidence of SuS expected in Israel and a 7-fold increase in the annual incidence expected in our medical center. Mean time from the onset of the symptoms to diagnosis was three weeks and follow-up time was twenty four months. Recent exposure to cytomegalovirus was serologically evident in three patients and one patient had high titer of anti-streptolysin antibody. All patients underwent brain MRI, fluorescein angiography and audiometry. All patients were treated according to the newly recommended guidelines. All patients achieved clinical and radiological stability. Conclusions We report of an increased incidence of SuS in Israel. Infectious serological findings may imply a post infectious mechanism. The use of the recommended diagnostic procedures reduced the time to diagnosis. Newly published treatment guidelines led to favorable clinical outcomes.

Background and Aims Occupational status may influence physical and mental post-stroke outcomes. We aimed to evaluate the association between occupational status and type, or engagement in social and family activities, neuroimaging measures and cognitive decline (CD) in a prospective cohort of stroke patients. Methods We included 273 first-ever stroke survivors at working age. All patients underwent 3T MRI at admission, as well as clinical and cognitive assessments at admission, 6, 12 and 24 months thereafter. Results Ninty nine (36.3%) of the participants were unemployed prior to the stroke. Age, sex, work type, other comorbidities, stroke severity or location were not associated with return to work. Patients who returned to work (87.4%) had better cognitive results and less depressive symptoms than those who retired after the event. Pre-stroke unemployment was associated with diabetes mellitus, hypertension, dyslipidemia, depression, poorer cognitive scores and brain atrophy. During the follow-up, 11% developed CD. CD was more common among previously unemployed than employed participants (19.2% vs. 6.3%, p = 0.001). Multiple regression adjusted for risk factors, revealed that pre-stroke unemployment was an independent predictor of CD (HR, 3.0; 95% CI: 1.06–8.44). Furthermore, engagement in mentally stimulating jobs decreased the risk for CD. Conclusions Pre-stroke unemployment and post-stroke work disruption were each associated with depression and poorer cognitive performance up to two years post-stroke, as well as with brain atrophy at admission. Retirement after the stroke may increase the risk of developing CD. These results highlight the importance of continued employment in preserving cognitive abilities among stroke survivors.

Background: The short (s) allele of a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) is related to reduced serotonin transporter efficiency and an increased vulnerability to stress and mental disorders. The 5-HTTLPR s allele was reported as associate with hypothalamic-pituitary-adrenal (HPA)-axis reactivity to stress, depression and negatively impact on memory. Acute stroke is associated with elevated cortisol levels as part of the body’s reaction to a stress provoking event. We investigated whether 5-HTT genotype interacts with physiological stress to impact on outcome after stroke. Methods: Data from 485 non-depressed cognitively intact first-ever mild to moderate stroke patients from the TABASCO study were available. Patients underwent 3T MRI scans, saliva cortisol measure and comprehensive neuropsychological assessments at admission, 6, and 12 and 24 months thereafter. Results: Carriers of the 5-HTT-s allele (23.2%) had significantly higher admission bedtime salivary cortisol (p=0.042) and more depressive symptoms 12 and 24 months after the index event (p=0.043, p=0.05, respectively) than non-carriers. Higher admission salivary cortisol levels negatively correlated with hippocampal and amigdalar volume at admission (r=-0.257, p=0.004; r=-0.177, p=0.048, respectively) as well as with lower cognitive and higher depression scores 24 months post-stroke (r=-0.2, p=0.032, r=0.245, p=0.007, respectively). The association between salivary cortisol levels, depressive and cognitive scores was stronger in 5-HTT-s carriers than non-carriers. Conclusions: We report that carriers of the 5-HTT-s allele may be at risk to develop depressive symptoms post-stroke. The interactive effects of the s allele and cortisol levels on hippocampal volume and post-stroke depressive symptoms, as well as cognitive performance, suggest that the negative effect of the serotonin polymorphism on the development of post-stroke depression and cognitive decline is mediated by the HPA axis. Since genetic factors may influence vulnerability to the adverse effects of stress, serotonin receptors may provide a novel target for therapeutics to prevent depression and cognitive deterioration in stroke patients.

BACKGROUND AND OBJECTIVE Previous studies suggest that excessive cortisol levels after stroke are associated with cognitive dysfunction. However, limited data exist regarding associations between post-stroke cortisol levels, brain abnormalities, genetic factors, and cognitive outcome. We sought to study these issues in a longitudinal stroke survivors cohort. METHODS Data from 182 cognitively intact ischemic stroke patients from the TABASCO study were available. Saliva cortisol levels (bedtime and post-awakening) and cognitive assessments were obtained on admission, and 6, 12, and 24 months thereafter. During hospitalization, patients underwent 3T MRI scans and APOE genotyping. RESULTS Higher bedtime cortisol levels immediately post-stroke were associated with larger neurological deficits (p

Background Stroke is a major cause of cognitive impairment and dementia. However, the underlying mechanisms beyond post-stroke cognitive impairment (PSCI) are not fully explained to date. Objective We studied the contribution of vascular pathology measures to PSCI, separate from and in conjunction with pathologic markers associated with Alzheimer's disease (AD). Methods Data from 397 cognitively intact ischemic stroke patients were available. All patients underwent 3T MRI and evaluated for white matter hyperintensity volume (WMHV) and integrity, ischemic lesions, small vessel disease (SVD) markers and grey matter (GM), hippocampal and cerebrospinal fluid (CSF) volumes. Comprehensive cognitive tests were performed on admission and after two years. We used multiple regression to evaluate the contributions of vascular pathology measures (Framingham risk score, WMHV, and existence of SVD) and AD-associated markers (apolipoprotein E4 status and hippocampal volume). Results During two years follow-up, 80 participants (20.2%) developed PSCI. Low GM and cortex volume and high WMHV and CSF volume, but not the new lesion volume, predicted the development of PSCI in a dose-dependent relationship (p = 0.001). Vascular related imaging markers and risk factors predicted PSCI better than AD related markers (p Conclusions Brain structural measures, including total GM volume, WMHV, and CSF volume were independently associated with PSCI and may serve as early biomarkers for risk prediction. In our sample, vascular pathology measures contributed significantly better to PSCI prediction than markers associated with AD. The newly detected ischemic lesion has not emerged as biomarker for PSCI risk, thus maybe a part of the ongoing vascular pathology.

Contains fulltext : 208975.pdf (Publisher’s version ) (Open Access) BACKGROUND: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. METHODS: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. FINDINGS: Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1.34 years [IQR 0.19-2.44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1.35 (95% CI 1.20-1.50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2.45 (1.82-3.29) for intracranial haemorrhage and 1.23 (1.08-1.40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4.55 [95% CI 3.08-6.72] for intracranial haemorrhage vs 1.47 [1.19-1.80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5.52 [3.36-9.05] vs 1.43 [1.07-1.91]; and for >/=20 cerebral microbleeds, aHR 8.61 [4.69-15.81] vs 1.86 [1.23-1.82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48-84] per 1000 patient-years vs 27 intracranial haemorrhages [17-41] per 1000 patient-years; and for >/=20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years). INTERPRETATION: In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden. FUNDING: British Heart Foundation and UK Stroke Association.

Background Many patients with large vessel occlusion (LVO) who are otherwise candidates for endovascular treatment (EVT) have had previous strokes. We aimed to examine the effect of previous stroke on outcome after EVT. Methods Consecutive patients with LVO were prospectively entered into a National Acute Stroke registry of patients undergoing EVT. Patients treated with EVT were divided into those with and without previous strokes. The rates of favorable reperfusion status, mortality, and excellent outcome at 90 days post-stroke as well as symptomatic intracranial hemorrhage (sICH) were evaluated. Results A total of 390 underwent EVT and 35 had previous strokes. Patients with previous strokes were significantly older; more frequently had a history of prior myocardial infarction and more often had pre-existing functional disability. Favorable target vessel recanalization was less frequently achieved in patients with previous strokes (60% vs. 82%; p = 0.005) and ordinal regression analysis for functional outcome revealed higher frequency of deterioration at three months in patients with previous strokes. Nevertheless, 9% of these patients maintained their previous disability state and sICH rates did not differ between the groups. Mortality rates at one year post stroke were significantly higher in patients with previous strokes (37% vs. 16%; p = 0.005). Conclusions Previous strokes are associated with higher likelihoods of mortality and unfavorable outcome in patients with LVO undergoing EVT. However, because some of these patients maintain their previous disability state, the presence of previous stroke should not be used as an exclusion criterion from EVT.

Background B-mode and Color Doppler ultrasonography (CDUS) are the methods of choice for screening and determining the degree of Carotid artery stenosis. The evaluation of stenosis with calcification may be hampered by a common CDUS artifact known as acoustic shadow (AS). Our objective was to assess the change in reliability of CDUS readings in the presence of an AS artifact. Methods Single center retrospective observational study. Included were patients with either an AS artifact or high-grade stenosis (defined by peak systolic velocity (PSV) > 240 cm/s) demonstrated in CDUS, and had a CT angiography (CTA) done within 6 months of the sonographic exam. All subjects were identified through the Tel-Aviv Sorasky medical center (TASMC) CDUS unit registry from which clinical information was extracted. CDUS images were manually reviewed grading AS magnitude. All CTAs were reviewed and reconstructed for accurate assessment of percent stenosis and were used as gold standard. Results The study cohort included 227 consecutive patients (corresponding with 454 internal carotid arteries) meeting inclusion criteria. 43.2% of the arteries (n = 195) had an AS artifact present on CDUS, regardless of percent stenosis, with a large artifact present in 6.7% arteries (n = 30). Older age was significantly related to the presence of AS artifact (p

Supplemental Material for Impact of previous stroke on outcome after thrombectomy in patients with large vessel occlusion by Ronen R Leker, Jose E Cohen, Anat Horev, David Tanne, David Orion, Guy Raphaeli, Jacob Amsalem, Jonathan Y Streifler, Hen Hallevi, Natan M Bornstein, Nour E Yaghmour, Gregory Telman and On Behalf of the NASIS-REVASC Study Group: for the ECASS-4 study group in International Journal of Stroke

Background and Aims: Patients with emergent large-vessel occlusion (ELVO) that present earlier than 4 h from onset are usually treated with bridging systemic thrombolysis followed by endovascular thrombectomy (EVT). Whether direct EVT (dEVT) could improve the chances of favorable outcome remains unknown. Methods: Consecutively, prospectively enrolled patients with ELVO presenting within 4 h of onset were entered into a National Acute Stroke Registry of patients undergoing revascularization. Patients treated with bridging were compared to those treated with dEVT. Excellent outcome was defined as having a modified Rankin Scale score ≤1 at 90 days following stroke. Results: Out of 392 patients that underwent thrombectomy, 270 (68%) presented within 4 h and were included. Of those, 159 (59%) underwent bridging and 111 (41%) underwent dEVT. Atrial fibrillation and congestive heart failure were more common in the dEVT group (43 vs. 30%, p = 0.04 and 20 vs. 8%, p = 0.009, respectively), but other risk factors, demographics, stroke severity and subtypes as well as baseline vessel patency state and time metrics did not differ. Excellent target vessel recanalization defined as TICI 3 (thrombolysis in cerebral infarction score) was more common in the dEVT group (75 vs. 61%, p = 0.03), but in-hospital mortality, discharge destinations, short- and long-term excellent outcome rates did not differ. On multivariate regression analysis, treatment modality did not significantly modify the chances of excellent outcome at discharge (OR 0.7; 95% CI 0.3–1.5) or at 3 months (OR 0.78 95% CI 0.4–1.4). Conclusions: The chances of attaining excellent functional outcomes are similar in ELVO patients undergoing dEVT or bridging.

Background: Stroke considerably increases the risk of dementia, while occupational status may influence physically and mentally long-term outcome after the event. We aimed to evaluate the interrelationship between occupational status, brain pathology on imaging and cognitive decline in a longitudinal post-stroke cohort. Methods: Data from 252 persons at working age ( Results: The working rate before stroke was 68.7%, and 60.4% 12 months later. Pre-stroke unemployment was associated with reduced cortical thickness and white matter volume, severity of the neurological deficit, poorer cognitive scores at 12 and 24 months, higher depression scores, and elevated inflammation (p=0.002, p=0.049, p=0.001, p=0.002, p Conclusions: Pre-stroke unemployment was independently associated with brain atrophy, depression, higher mortality, and poorer performance in cognitive evaluation 2 years post-stroke. T2DM, stroke severity and pre-stroke unemployment were independent predictors of this decline, as well as early retirement after the stroke. These results emphasizing the advantage of employment versus early retirement in an attempt to reserve health and cognitive abilities.

The hippocampus is known to play a vital role in learning and memory and was demonstrated as an early imaging marker for Alzheimer's disease (AD). However, its role as a predictor for mild cognitive impairment and dementia following stroke is unclear. The main purpose of this study was to examine the associations between hippocampal volume, mean diffusivity (MD) and connectivity and cognitive state following stroke. Eighty three consecutive first ever mild to moderate stroke or transient ischemic attack (TIA) survivors from our ongoing prospective TABASCO (Tel Aviv Brain Acute Stroke Cohort) study underwent magnetic resonance imaging scans within 7 days of stroke onset. Hippocampal volume was measured from T1 weighted images, hippocampal mean diffusivity was calculated from diffusion tensor imaging and connectivity was calculated from resting state fMRI. Global cognitive assessments were evaluated during hospitalization and 6 and 12 months later using a computerized neuropsychological battery. Multiple linear regression analysis was used to test which of the hippocampi measurements best predict cognitive state. All three imaging parameters were significantly correlated to each other (|r's| >0.3, P's

Background and Purpose— Patients with stroke are at risk for developing cognitive impairment. We tested whether the assessment of balance and gait can enhance the prediction of long-term cognitive outcome in stroke survivors. Methods— Participants were patients with first-ever, mild-moderate ischemic stroke or transient ischemic attack from the Tel Aviv Brain Acute Stroke Cohort (TABASCO) study, a large prospective cohort study, who underwent 3-T MRI and were followed for ≥2 years using neurological, neuropsychological, and mobility examinations 6, 12, and 24 months after the index event. Results— Data were available for 298 patients (age: 66.7±9.6 years). Forty-six participants (15.4%) developed cognitive decline (CD) over the 2 years of follow-up. The CD group and cognitively intact group did not differ in their neurological deficits or in their infarct volume or location. Nonetheless, 6 months after stroke, the Timed Up and Go test took longer in those who later developed CD ( P P P P =0.006). Separate analyses of the patients with transient ischemic attack revealed similar results. Multivariate regression analysis showed that Timed Up and Go times >12 s at 6 months after stroke/transient ischemic attack was a significant independent risk marker of CD 24 months after stroke (odds ratio=6.07, 95% confidence interval: 1.36–27.15). Conclusions— These results suggest that measures of balance and gait are significant risk markers of cognitive status 2 years after stroke. Relatively simple, performance-based tests of mobility may enhance the identification of stroke/transient ischemic attack survivors who have an increased risk of developing CD. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01926691.

Background and Purpose— Type 2 diabetes mellitus (T2DM) is associated with diseases of the brain, kidney, and vasculature. However, the relationship between T2DM, chronic kidney disease, brain alterations, and cognitive function after stroke is unknown. We aimed to evaluate the inter-relationship between T2DM, impaired renal function, brain pathology on imaging, and cognitive decline in a longitudinal poststroke cohort. Methods— The TABASCO (Tel Aviv brain acute stroke cohort) is a prospective cohort of stroke/transient ischemic attack survivors. The volume and white matter integrity, ischemic lesions, and brain and hippocampal volumes were measured at baseline using 3-T MRI. Cognitive tests were performed on 507 patients, who were diagnosed as having mild cognitive impairment, dementia, or being cognitively intact after 24 months. Results— At baseline, T2DM and impaired renal function (estimated creatinine clearance [eCCl] Conclusions— T2DM and impaired renal function are independently associated with abnormal brain structure, as well as poorer performance in cognitive tests, 2 years after stroke. The presence of both conditions quadruples the risk for cognitive decline. T2DM and lower eCCl have an independent and additive effect on brain atrophy and the risk of cognitive decline. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01926691.

It is unknown which patient will benefit most from hospital admission after transient ischemic attack (TIA). Our aim was to define predictors of a positive hospital outcome.We used two cohorts of TIA patients: the University of Texas at Houston Stroke Center (UTH); and Tel-Aviv Sourasky Medical Center in Israel (TASMC) for external validation. We retrospectively reviewed medical records and imaging data. We defined positive yield (PY) of the hospital admission as identification of stroke etiologies that profoundly changes clinical management.The UTH cohort included 178 patients. 24.7% had PY. In the multivariate analysis, the following were associated with PY: coronary disease (CAD); age; and acute infarct on DWI. We then derived a composite score termed the PY score to predict PY. One point is scored for: age60, CAD, and acute infarct on DWI. The proportion of PY by PY score was as follows: 0-6%; 1-22%; 2-47%; 3-67% (p0.001). In the validation cohort PY score was highly predictive of PY and performed in a very similar manner.Our data suggest, the PY score may enable physicians to make better admission decisions and result in better, safer and more economical care for TIA patients.

BACKGROUND The phenomenon of slow coronary flow (SCF) in the presence of normal coronary arteries may indicate endothelial dysfunction, which is characteristic of an early stage in the development of atherosclerosis. Measurement of the Carotid Intima-Media Thickness (CIMT) allows identification of early stages of atherosclerosis. CIMT might offer a non-invasive method of diagnosing SCF patients. Previous studies demonstrated conflicting results regarding the relationship between these two phenomena. In the present study, we examined the association between coronary flow velocity and the degree of CIMT in patients with angiographically normal coronary arteries. METHODS Coronary arterial blood flow velocity was measured using two methods - Corrected Thrombolysis in Myocardial Infarction (TIMI) Frame Count (CTFC) and Coronary Clearance Frame Count (CCFC). In addition, we measured the level of the CIMT using a special automated computerized software. RESULTS Seventy Five consecutive patients were prospectively recruited. No correlation was found between CIMT and mean CTFC (r = -0.08, p = NS) or mean CCFC (r = -0.07, p = NS). In addition, CIMT values did not differ between the SCF and the Normal coronary flow (NCF) groups (0.796 mm vs. 0.805 mm, respectively, p = 0.733). Patients with SCF had higher levels of hematocrit (39.9% vs. 36.1%, p < 0.001), LDL cholesterol (101.1 mg/dl vs. 85.8 mg/dl, p = 0.01) and higher rate of current smokers (28.9% vs. 10.8%, p = 0.05). CONCLUSIONS Patients with angiographically normal coronary arteries and SCF do not have increased CIMT values. However, current smoking, higher LDL cholesterol and hematocrit levels are all related to slower coronary blood flow.

Purpose Stroke imaging studies during the acute phase are likely to precede several vascular brain mechanisms, which have an important role in patient outcome. The aim of this study was to identify within the lesion area during the subacute phase (≥1 day) reactive tissue, which may have the potential for recovery. Methods Twenty seven stroke patients from two cohorts were included. MRI performed during the subacute phase included conventional, perfusion and diffusion imaging. In cohort I, unsupervised multiparametric classification of the lesion area was performed. In cohort II threshold based classification was performed during the subacute phase, and radiological outcome was assessed at follow-up scan. Results Three tissue classes were identified in cohort I, referred to as irreversibly damaged, intermediary, and reactive tissue. Based on threshold values defined in cohort I, the reactive tissue was identified in 11/13 patients in cohort II, and showed tissue preservation/partial recovery in 9/11 patients at follow-up scan. The irreversibly damaged tissue was identified in 7/13 patients in cohort II, and predicted tissue necrosis in all cases. Conclusion Identification of reactive tissue following stroke during the subacute phase can improve radiological assessment, contribute to the understanding of brain recovery processes and has implications for new therapeutic approaches. Magn Reson Med 72:1381–1388, 2014. © 2013 Wiley Periodicals, Inc.

a b s t r a c t Background: Lesion size in fluid attenuation inversion recovery (FLAIR) images is an important clinical parameter for patient assessment and follow-up. Although manual delineation of lesion areas consid- ered as ground truth, it is time-consuming, highly user-dependent and difficult to perform in areas of indistinct borders. In this study, an automatic methodology for FLAIR lesion segmentation is proposed, and its application in patients with brain tumors undergoing therapy; and in patients following stroke is demonstrated. Materials and methods: FLAIR lesion segmentation was performed in 57 magnetic resonance imaging (MRI) data sets obtained from 44 patients: 28 patients with primary brain tumors; 5 patients with recurrent- progressive glioblastoma (rGB) who were scanned longitudinally during anti-angiogenic therapy (18 MRI scans); and 11 patients following ischemic stroke. Results: FLAIR lesion segmentation was obtained in all patients. When compared to manual delineation, a high visual similarity was observed, with an absolute relative volume difference of 16.80% and 20.96% and a volumetric overlap error of 24.87% and 27.50% obtained for two raters: accepted values for automatic methods. Quantitative measurements of the segmented lesion volumes were in line with qualitative radiological assessment in four patients who received anti-anogiogenic drugs. In stroke patients the proposed methodology enabled identification of the ischemic lesion and differentiation from other FLAIR hyperintense areas, such as pre-existing disease. Conclusion: This study proposed a replicable methodology for FLAIR lesion detection and quantification and for discrimination between lesion of interest and pre-existing disease. Results from this study show the wide clinical applications of this methodology in research and clinical practice. © 2013 Published by Elsevier Ireland Ltd.

Background Acute ischemic stroke (AIS) is a common neurological event that causes varying degrees of disability. AIS outcome varies considerably, from complete recovery to complete loss of tissue and function. This diversity is partly explained by the compensatory ability of the collateral circulation and the ensuing cerebral flow grade. The collateral flow to the anterior circulation largely supplies the cortical areas. The deep brain tissue is supplied by penetrating arteries and has little or no collateral supply. Although these brain compartments differ substantially in their collateral supply, there are no published data on the different effects the collateral circulation has on them. In addition, the influence of baseline collateral flow on the final infarct size following endovascular or reperfusion therapies remains unknown. This study was designed to determine the effect of the collateral circulation on cortical infarct volume and deep infarct volume, and to investigate the relation between the collateral grade, response to reperfusion therapy and clinical outcome. Methods We studied consecutive patients presenting to our medical center between April 2008 and April 2012 with AIS and anterior proximal artery occlusion. To be included patients had to undergo a computerized tomographic angiographic study within 12 h of symptom onset demonstrating the occlusion. Imaging data and clinical and laboratory values were extracted retrospectively from the original scans and medical records. Cortical infarct volume (CIV) and deep infarct volume (DIV) were calculated as well as collateral grade. Clinical outcome was assessed at discharge using the modified Rankin Scale (mRS). Results Of the 51 study patients, 13 were treated conservatively, 22 received intravenous recombinant tissue plasminogen activator, and 16 received intra-arterial thrombolysis. The collateral grading was similar for all three treatment groups. While there was a moderate inverse correlation between the collateral grade and CIV (Spearman’s rho = −0.49, P

Neurofibromatosis type 1 (NF1) and its related disorders (NF1-Noonan syndrome (NFNS) and Watson syndrome (WS)) are caused by heterozygous mutations in the NF1 gene. Pulmonary stenosis (PS) occurs more commonly in NF1 and its related disorders than in the general population. This study investigated whether PS is associated with specific types of NF1 gene mutations in NF1, NFNS and WS. The frequency of different NF1 mutation types in a cohort of published and unpublished cases with NF1/NFNS/WS and PS was examined. Compared with NF1 in general, NFNS patients had higher rates of PS (9/35=26% vs 25/2322=1.1%, P value

Background: Progression of neurological deficit (PND) is a frequent complication of acute subcortical ischemic stroke (SCS). The role of intracranial atherosclerosis (IAS) in PND is controversial. Our goal was to evaluate IAS on admission, as predictor of PND in SCS patients. Methods: SCS patients were identified from our prospective database from 2004 to 2008. Clinical and laboratory data were collected from charts, and radiographic data from original radiographs. The proximal intracranial arteries were graded as patent, irregular, stenotic, or occlusion. IAS was defined as irregularity or stenosis. PND was defined as a change in the National Institutes of Health Stroke Scale >1 point. Results: Two hundred and two SCS patients were identified. In 14%, PND occurred at a median of 2 days from onset. Univariate analysis by infarct location showed the following to be associated with PND: for anterior circulation infarcts (centrum semiovale/basal ganglia), M1 atherosclerosis (p = 0.042); for posterior circulation infarcts, vertebral artery atherosclerosis (p = 0.018). For both groups, we found a non-significant association with age (p = 0.2) and HbA1c levels (p = 0.095). No association was found with admission glucose levels. Multivariate analysis showed the following association with PND: for anterior circulation infarcts, M1 atherosclerosis (OR 4.7; 95% CI 1.2–18.8; p = 0.03); for pontine infarcts, vertebral artery atherosclerosis (OR 5.8; 95% CI 1.1–29.4; p = 0.033). There was an increase in PND likelihood with an increasing number of atherosclerotic vessels. Discussion: In our cohort of SCS patients, PND was associated with IAS of the responsible vessels. These results suggest a role for IAS in the pathogenesis of PNF in SCS patients.

Background Recent studies have demonstrated that even survivors of mild stroke experience residual damage, which persists and in fact increases in subsequent years. About 45% of stroke victims remain with different levels of disability. Identifying factors associated with poststroke cognitive and neurological decline could potentially yield more effective therapeutic opportunities. Aims and hypothesis We hypothesize that data based on biochemical, neuroimaging, genetic and psychological measures can, in aggregate, serve as better predictors for subsequent disability, cognitive and neurological deterioration, and suggest possible interventions. Design The Tel-Aviv Brain Acute Stroke Cohort (TABASCO) study is an ongoing, prospective cohort study that will recruit approximately 1125 consecutive first-ever mild–moderate stroke patients. It is designed to evaluate the association between predefined demographic, psychological, inflammatory, biochemical, neuroimaging and genetic markers, measured during the acute phase, and long-term outcome: subsequent cognitive deterioration, vascular events (including recurrent strokes), falls, affect changes, functional everyday difficulties and mortality. Discussion This study is an attempt to comprehensively investigate the long-term outcome of mild–moderate strokes. Its prospective design will provide quantitative data on stroke recurrence, the incidence of other vascular events and the evaluation of cognitive, affective and functional decline. Identifying the factors associated with poststroke cognitive and functional decline could potentially yield more effective therapeutic approaches.

Background: The ‘spot sign’ is a bright spot on computerized tomography angiography (CTA) source images predictive of hematoma growth. Contrast extravasation (CE) is seen on routine head CT following CTA as pooling of contrast within the hematoma. Our aim was to re-evaluate the predictive value of both the spot sign and CE and measure the reliability of scoring them. Methods: Consecutive cases of spontaneous intracerebral hemorrhage (ICH) presenting within 4 h. The presence of a ‘spot’ and CE, ICH and intraventricular hemorrhage volume at baseline and on follow-up scans were assessed. Clinical outcome was captured using the modified Rankin Scale on hospital discharge. Results: We identified 28 patients with a mean age of 56.8 years, median ICH volume of 19 ml, and median NIH Stroke Scale score on admission of 17.5. 11/27 (40.7%) had a positive spot and 13/22 (59.1%) had CE. Interrater reliability was 0.812 (95% CI 0.57–0.91, p < 0.001) for the spot sign and 0.952 (95% CI 0.89–0.98, p < 0.001) for CE. ICH volume increased in 16/28 (57.1%) patients. Both the spot sign and CE were associated with ICH growth (p < 0.001) and poor outcome (p < 0.001). Conclusions: In ICH patients, the presence of the spot sign or CE is highly correlated with early ICH growth. In our experience, CE is a more sensitive predictor of ICH growth with a better negative predictive value than the spot sign; CE is more consistently identified even by experienced clinicians. Postcontrast CT should be done routinely after CTA in patients presenting with ICH within 4 h. Patients who are CE-positive may be candidates for hemostatic therapies or early surgical intervention.

Background Both caffeinol and hypothermia are neuroprotective in preclinical models of transient middle cerebral artery occlusion. We tested whether combining caffeinol and hypothermia with tissue plasminogen activator (t-PA) in patients with acute stroke is safe and feasible. Methods Twenty patients with acute ischemic stroke were treated with caffeinol (caffeine 8-9 mg/kg + ethanol 0.4 g/kg intravenously [IV] × 2 hours, started by 4 hours after symptom onset) and hypothermia (started by 5 hours and continued for 24 hours [target temperature 33-35°C] followed by 12 hours of rewarming). IV t-PA was given to eligible patients. Meperidine and buspirone were used to suppress shivering. Results All patients received caffeinol, and most reached target blood levels. Cooling was attempted in 18 patients via endovascular (n = 8) or surface (n = 10) approaches. Two patients were not cooled due to catheter or machine failure. Thirteen patients reached target temperature; average time from symptom onset was 9 hours and 43 minutes. The last 5 hypothermia patients received surface cooling with iced saline induction and larger doses of meperidine; all patients reached target temperature, on average within 2 hours and 30 minutes from induction and 6 hours and 21 minutes from symptom onset. Three patients died: one from symptomatic hemorrhage, one from malignant cerebral edema, and one from unrelated medical complications. No adverse events were attributed to caffeinol. One patient had reduced respiratory drive due to meperidine, requiring BiPAP. Discussion Combining caffeinol with hypothermia in patients with acute stroke given IV t-PA is feasible. A prospective placebo-controlled randomized study is needed to further assess safety and to test the efficacy of caffeinol, hypothermia, or both.

Background: Ischemic stroke is a leading cause of morbidity. Assessing the chances of recovery is critical to optimize poststroke care. Methods: We used a cohort of patients from the Virtual International Stroke Trial Archive that participated in acute stroke trials (control arm) and were followed for 90 days. The cohort was grouped by day 7 (D7) modified Rankin scale (mRS) scores. Variables that were associated with good outcome (mRS 0–2 at 90 days) in the univariate analysis were entered into a logistic regression model to determine the independent good outcome criteria for each D7 mRS tier. Results: We analyzed 1,798 patients. The independent good outcome criteria identified for different mRS tiers were: D7 mRS of 3: age ≤70, 0–2 vascular risk factors, D7 NIH Stroke Scale (NIHSS) arm strength ≤1, D7 NIHSS language score = 0; D7 mRS of 4: age ≤70, male, D7 NIHSS facial palsy ≤1, D7 NIHSS visual = 0, D7 NIHSS leg strength ≤1, D7 NIHSS dysarthria = 0; D7 mRS of 5: age ≤70, IV tPA treatment, D7 NIHSS dysarthria = 0, D7 NIHSS leg strength ≤2. For each mRS tier, we observed a graded increase in the percentage of the primary and secondary end points with increase in the number of criteria. Conclusions: We identified clinical variables that predict good outcome, are specific to each day 7 mRS tier, and enable easy and informative assessment of the patient’s likelihood of achieving varying degrees of recovery at day 90. These results may be useful in both clinical practice and research but require validation in an independent patient cohort.

Background: There is no proven treatment for stroke progression in patients with subcortical infarcts. Eptifibatide, a glycoprotein IIb/IIIa inhibitor, might halt stroke progression by improving flow in the microcirculation. Methods: We conducted a retrospective analysis of patients with subcortical stroke who experienced deterioration and were treated with eptifibatide (loading dose 180 μg/kg; infusion 2 μg/kg/min) for 24–48 h. Oral antiplatelet agents were started 6 h before discontinuation of eptifibatide. Results: Twenty-four patients with subcortical strokes were treated. The median admission NIHSS score was 5.0, which worsened to 8.5 (motor 5.0) before starting eptifibatide. The median NIHSS score 24 h after starting eptifibatide was 5.5. At 24 h, 42% had motor NIHSS scores less than or equal to pre-deterioration scores (50% for total NIHSS), and 50% had improved at least 1 motor point compared to pre-eptifibatide scores, which was sustained until hospital discharge. At discharge, the median total NIHSS score was 4.5. Ninety-two percent of patients were discharged home or to inpatient rehabilitation. Treatment was stopped early in 1 case due to a platelet drop Conclusions: Eptifibatide infusion may be safe in patients with subcortical ischemic strokes. Future studies are needed to test the safety and potential efficacy of this agent in subcortical stroke progression.

Objective To examine whether depressive symptoms after a stroke or a transient ischemic attack (TIA) increase the risk of cognitive impairment and functional deterioration at 2-year follow-up. Methods Participants were survivors of first-ever, mild-to-moderate ischemic stroke or TIA from the TABASCO prospective cohort study who underwent 3T magnetic resonance imaging and were examined by a multiprofessional team 6, 12, and 24 months after the event using direct interviews, depression scales, and neurologic, neuropsychological, and functional evaluations. The main outcome was the development of cognitive impairment, either mild cognitive impairment (MCI) or dementia. MCI was diagnosed by a decline on at least 1 cognitive domain (≥ 1.5 SD) of the Montreal Cognitive Assessment score and/or on the computerized neuropsychological battery, as compared with age- and education-matched published norms. Dementia was diagnosed by a consensus forum that included senior neurologists specializing in memory disorders and a neuropsychologist. Results Data were obtained from 306 consecutive eligible patients (mean age: 67.1 ± 10.0 years) who were admitted to the department of emergency medicine at the Tel Aviv Medical Center from April 1, 2008, to December 1, 2011, within 72 hours from onset of symptoms of TIA or stroke. Of these patients, 51 (16.7%) developed cognitive impairment during a 2-year follow-up. Multivariate regression analysis showed that a Geriatric Depression Scale (GDS) score ≥ 6 at admission and at 6 months after the event was a significant independent marker of cognitive impairment 2 years after the stroke/TIA (OR = 3.62, 95% CI, 1.01-13.00; OR = 3.68, 95% CI, 1.03-13.21, respectively). A higher GDS score at 6 months was also related to a worse functional outcome (P Conclusions Our results support depression screening among stroke and TIA survivors as a tool to identify patients who are prone to have a worse cognitive and functional outcome. These patients may benefit from closer medical surveillance and a more intensive treatment approach. Trial registration ClinicalTrials.gov identifier: NCT01926691.

article Background: In 45% of cases of intracerebral hemorrhage (ICH) the hematoma extends into the ventricles (IVH). Intraventricular inflammation may be one mechanism by which IVH exerts deleterious effects. Tissue plasminogen activator instillation into the ventricles (IVT) has been studied for the treatment of IVH; however, its effect on IVH-induced inflammation is unknown. The purpose of this work was to describe the inflammatory response in the CSF following IVH and compare it in patients treated or not treated with IVT. Methods: Consecutive patients diagnosed with IVH and treated with ventriculostomy were selected from our prospective stroke registry from November 2004 to July 2007. CSF protein, glucose, and WBC (corrected for RBC number) from samples collected up to 19 days after IVH were captured. Patients with evidence of CSF infection were excluded. Results: 29 patients were identified: 18 in the IVT group and 11 in the non-IVT group. The two groups were comparable in terms of stroke severity and IVH volume. A brisk cellular inflammatory reaction developed around day 2, lasted 5 days and then subsided. IVT seemed to attenuate this response. There were no differences in clinical outcomes between groups. Conclusions: IVH induces intrathecal inflammatory response that peaks at day 5. IVT appears to modify this inflammation. Further work is needed to study the relationship between the intraventricular inflammatory response and patient outcome.

Objective: The purpose of this study was to assess the incidence of deterioration, fluctuation, and associated risk of poor outcome in patients with subcortical stroke (SCS). Methods: We conducted a prospective observational study, enrolling patients admitted with SCS based on their clinical examination and imaging studies. An NIH Stroke Scale evaluation was performed daily and whenever deterioration in examination was detected. Neurologic deterioration was defined as a motor score increase of at least 1 on the NIH Stroke Scale. Modified Rankin Scale scores at discharge were used to assess outcome. Results: Among 90 enrolled patients, 37 (41%) deteriorated, 75% of them in the first 24 hours after enrollment. Administration of tissue plasminogen activator was significantly associated with deterioration (hazard ratio 2.25; 95% confidence interval [CI]: 1.13–4.49) even after controlling for the association of deterioration with the early poststroke period. Deterioration conferred an increased risk of poor outcome (modified Rankin Scale scores 3–6) at discharge (relative risk: 1.80; 95% CI: 1.71–1.93). Reversion back to predeterioration deficits occurred in 38% of patients, and was associated with reduced risk of poor outcome at discharge (relative risk: 0.12; 95% CI: 0.02–0.83). Treatment with tissue plasminogen activator conferred better chances of spontaneous recovery to predeterioration deficits after initial deterioration (hazard ratio: 4.36; 95% CI: 1.36–14.01). Conclusion: More than 40% of patients with SCS deteriorate neurologically. Deterioration tends to occur early after stroke, spontaneously reverses in approximately one-third of cases, and poses an increased risk of poor outcome. Therapies are needed to prevent, arrest, or reverse deterioration in patients with SCS.

Background and Purpose— Recombinant-activated factor VII (rFVIIa) is an investigational treatment for intracerebral hemorrhage (ICH). We have evaluated the drug’s treatment effect based on time to treatment. Methods— ICH patients treated up to 4 hours from symptom onset were divided based on time to treatment: ≤3 hours (3H) and 3 to 4 hours (4H). Head CT was done at baseline and 24 hours. Outcome measures included: ICH growth at 24 hours, mortality, favorable outcome and discharge disposition. A cohort of nontreated matched ICH patients was used to asses the clinical efficacy. Results— Forty-six patients were treated with rFVIIa: 24 in the 3H group (range 70 to 180 minutes), 22 in the 4H group (range 181 to 300). One hundred and forty-eight patients formed the control group. Mean baseline ICH volume was 8.8 mL for 3H and 10.1 mL for 4H. Mean 24-hour volume was 9.3 mL for 3H (absolute increase 1.05 mL, relative increase 11.9%) and 11.5 mL for 4H (absolute increase 1.1 mL, relative increase 10.9%); P =0.47 is for the difference in relative increase. Mortality was 12.5% for 3H group, 13.6% for 4H, and 13.1% for the control. In the 3H group, 58.3% were discharged with a poor outcome, compared with 54.5% in 4H and 54.1% in the control. Thrombotic adverse events occurred in 11.1% of patients treated with rFVIIa. Conclusions— In our off-label with rFVIIa, we did not find evidence of a treatment effect based on time to treatment. Other criteria should be sought to identify patients who might benefit clinically from rFVIIa.

Background and Purpose— Intra-arterial therapy (IAT) promotes recanalization of large artery occlusions in acute ischemic stroke. Despite high recanalization rates, poor clinical outcomes are common. We attempted to optimize a score that combines clinical and imaging variables to more accurately predict poor outcome after IAT in anterior circulation occlusions. Methods— Patients with acute ischemic stroke undergoing IAT at University of Texas (UT) Houston for large artery occlusions (middle cerebral artery or internal carotid artery) were reviewed. Independent predictors of poor outcome (modified Rankin Scale, 4–6) were studied. External validation was performed on IAT-treated patients at Emory University. Results— A total of 163 patients were identified at UT Houston. Independent predictors of poor outcome ( P ≤0.2) were identified as score variables using sensitivity analysis and logistic regression. Houston Intra-Arterial Therapy 2 (HIAT2) score ranges 0 to 10: age (≤59=0, 60–79=2, ≥80 years=4), glucose (P P =0.02). Results from the cohort of Emory (198 patients) were consistent; patients with HIAT2 score ≥5 had 6× greater odds of poor outcome at discharge and at 90 days. HIAT2 outperformed other previously published predictive scores. Conclusions— The HIAT2 score, which combines clinical and imaging variables, performed better than all previous scores in predicting poor outcome after IAT for anterior circulation large artery occlusions.

Background and Purpose— Inflammation may contribute to cognitive impairment after stroke. Inflammatory markers are associated with hippocampal atrophy. We tested whether markers of inflammation, erythrocyte sedimentation rate (ESR), and serum levels of C-reactive protein are associated with reduced hippocampal volume and poor cognitive performance among stroke survivors. Methods— We analyzed 368 consecutive cases from our prospective study of first-ever mild–moderate stroke patients. MRI, cognitive tests, and inflammatory markers were determined. Patients were reevaluated 6 and 12 months after the event. Results— ESR remained unchanged in follow-up examinations, suggesting a chronic inflammation background in some patients. Higher levels of C-reactive protein and ESR were associated with worse performance in cognitive tests, particularly memory scores. This association was maintained for ESR (but not C-reactive protein) after adjustment for confounders ( P =0.002). Patients with smaller hippocampi had inferior cognitive results. Moreover, in a multivariate regression model, higher ESR values (but not C-reactive protein) were related to reduced hippocampal volume ( P =0.049). Conclusions— This report shows a strong relationship between ESR and hippocampal volume, as well as with cognitive performance among poststroke patients. This could plausibly relate to incipient cognitive decline via hippocampal pathways.

E. Kliper, E. Ben Assayag, S. Shenhar-Tsarfaty, L. Shopin, H. Hallevi, E. Uriel, A. Korczyn A, N. M. Bornstein, T. Hendler, O. Aizenstein, and D. Ben Bashat D The Wohl institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, Departments of Neurology, Tel Aviv Sourasky Medical Center, Israel, Israel, Departments of Radiology, Tel Aviv Sourasky Medical Center, Israel, Israel, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Israel, Israel

Background and Purpose— Patients with intracerebral hemorrhage (ICH) are at high risk for development of deep venous thrombosis. Current guidelines state that low-dose subcutaneous low molecular weight heparin or unfractionated heparin may be considered at 3 to 4 days from onset. However, insufficient data exist on hematoma volume in patients with ICH before and after pharmacological deep venous thrombosis prophylaxis, leaving physicians with uncertainty regarding the safety of this practice. Methods— We identified patients from our stroke registry (June 2003 to December 2007) who presented with ICH only or ICH+intraventricular hemorrhage and received either low molecular weight heparin subcutaneously or unfractionated heparin within 7 days of admission and had a repeat CT scan performed within 4 days of starting deep venous thrombosis prophylaxis. We calculated the change in hematoma volume from the admission and posttreatment CTs. Hematoma volume was calculated using the ABC/2 method and intraventricular hemorrhage volumes were calculated using a published method of hand drawn regions of interest. Results— We identified 73 patients with a mean age of 63 years and median National Institutes of Health Stroke Scale score 11.5. The mean baseline total hematoma volume was 25.8 mL±23.2 mL. There was an absolute change in hematoma volume from pre- and posttreatment CT of −4.3 mL±11.0 mL. Two patients developed hematoma growth. Repeat analysis of patients given pharmacological deep venous thrombosis prophylaxis within 2 or 4 days after ICH found no increase in hematoma size. Conclusions— Pharmacological deep venous thrombosis prophylaxis given subcutaneously in patients with ICH and/or intraventricular hemorrhage in the subacute period is generally not associated with hematoma growth.

Objectives: Antiplatelet therapy (APT) promotes bleeding; therefore, APT might worsen outcome in patients with intracerebral hemorrhage (ICH). We performed a systematic review and meta-analysis to address the hypothesis that pre-ICH APT use is associated with mortality and poor functional outcome following ICH. Methods: The Medline and Embase databases were searched in February 2008 using relevant key words, limited to human studies in the English language. Cohort studies of consecutive patients with ICH reporting mortality or functional outcome according to pre-ICH APT use were identified. Of 2,873 studies screened, 10 were judged to meet inclusion criteria by consensus of 2 authors. Additionally, we solicited unpublished data from all authors of cohort studies with >100 patients published within the last 10 years, and received data from 15 more studies. Univariate and multivariable-adjusted odds ratios (ORs) for mortality and poor functional outcome were abstracted as available and pooled using a random effects model. Results: We obtained mortality data from 25 cohorts (15 unpublished) and functional outcome data from 21 cohorts (14 unpublished). Pre-ICH APT users had increased mortality in both univariate (OR 1.41, 95% confidence interval [CI] 1.21 to 1.64) and multivariable-adjusted (OR 1.27, 95% CI 1.10 to 1.47) pooled analyses. By contrast, the pooled OR for poor functional outcome was no longer significant when using multivariable-adjusted estimates (univariate OR 1.29, 95% CI 1.09 to 1.53; multivariable-adjusted OR 1.10, 95% CI 0.93 to 1.29). Conclusions: In cohort studies, APT use at the time of ICH compared to no APT use was independently associated with increased mortality but not with poor functional outcome.

Angiosarcoma (AS) is a rare understudied soft tissue sarcoma exhibiting endothelial cell differentiation. We sought to evaluate AS natural history in the largest patient cohort reported to date and further unravel commonly deregulated molecular events of potential therapeutic utility.Medical records of AS patients (n = 222) treated at our institution from 1993 to 2007 were reviewed. Univariable and multivariable analyses were used to identify independent outcome prognosticators. An AS tissue microarray (n = 68 human specimens) was constructed for immunohistochemical analysis of multiple potential drugable kinase-related molecular markers.Forty-three (19.4%) metastatic AS patients and 179 patients (80.6%) with localized disease were included. Median survival of localized versus metastatic AS was 49 (range, 2-188) versus 10 (range, 1-69) months (P0.0001). Patients with localized AS who underwent complete surgical resection (n = 136; 76%) demonstrated significantly better outcome compared with those with unresectable tumors (n = 43; 24%; P0.0001). Of several factors identified on univariable analysis as significantly adverse for disease-specific survival, tumor size (5 cm vs.or = 5 cm, P = 0.01) and epithelioid histologic component (P = 0.008) remained significant on multivariable analysis as independent adverse prognosticators in complete resection patients. Immunohistochemistry identified significant overexpression of vascular endothelial growth factor-A and C as well as p-AKT, p-4EBP1, and eIF4E in human AS.AS harbors a dismal outcome and even patients with disease amenable to complete surgical resection exhibit a 5-year disease-specific survival of only 53%. There is a crucial need for better therapies. Data presented here support further study of the AKT/mTOR pathway as novel molecular targets for AS therapy.

Background and Purpose— Cocaine is a cause of intracerebral hemorrhage (ICH), but there are no large studies that have characterized the location, pathology, and outcome of patients with cocaine-associated ICH. Methods— We performed a retrospective analysis of all patients admitted to our stroke service from 2004 to 2007 who had nontraumatic ICH and urine drug screens positive for cocaine and compared them with similar patients who had negative drug screens for cocaine. Results— We identified 45 patients with cocaine-associated ICH and 105 patients with cocaine-negative ICH. There were no significant differences in age or gender, but there was a significantly higher incidence of black patients in the cocaine-positive group. Cocaine-associated ICH patients had higher admission blood pressures, significantly more subcortical hemorrhages, and higher rates of intraventricular hemorrhage compared to patients with cocaine-negative ICH. Cocaine-positive patients had worse functional outcome, defined as modified Rankin Scale score >3 at the time of discharge (OR, 4.90; 95% CI, 2.19–10.97), and were less likely to be discharged home or to inpatient rehabilitation. Patients with cocaine-associated ICH were nearly 3-times more likely to die during their acute hospitalization when compared to cocaine-negative patients. Conclusion— Recent cocaine ingestion is associated with hemorrhages that occur more frequently in subcortical locations, have a higher risk of intraventricular hemorrhage, and have a poor prognosis compared to patients with cocaine-negative, spontaneous ICH.

Background and Purpose— The safety of thrombolytic therapy in patients with cocaine-associated acute ischemic stroke (CIS) is unknown. Methods— We conducted a retrospective review of patients with CIS who presented to our stroke center. Thrombolytic treatment was compared between cocaine-positive (n=29) and cocaine-negative (n=75) patients. We also compared patients with CIS treated with tissue plasminogen activator versus those who did not receive tissue plasminogen activator (n=58). Safety outcomes were determined by the incidence of symptomatic intracerebral hemorrhage, in-hospital mortality, and modified Rankin Scale at hospital discharge. Results— There were no complications in tissue plasminogen activator-treated patients with CIS. Cocaine-positive and cocaine-negative treated patients had similar stroke severity and safety outcomes. Patients with CIS treated with tissue plasminogen activator had more severe strokes on baseline National Institutes of Health Stroke Scale but similar safety outcomes compared with nontreated patients with CIS. Conclusion— Thrombolytic therapy for CIS appears to be safe in this small study. Further research is needed to more definitively assess safety and efficacy of tissue plasminogen activator for CIS.

Background and Purpose— Intra-arterial recanalization therapy (IAT) is increasingly used for acute stroke. Despite high rates of recanalization, the outcome is variable. We attempted to identify predictors of outcome that will enable better patient selection for IAT. Methods— All patients who underwent IAT at the University of Texas Houston Stroke Center were reviewed. Poor outcome was defined as modified Rankin Scale score 4 to 6 on hospital discharge. Findings were validated in an independent data set of 175 patients from the University of California at Los Angeles Stroke Center. Results— One hundred ninety patients were identified. Mean age was 62 years and median baseline National Institutes of Health Stroke Scale score was 0.18. Recanalization rate was 75%, symptomatic hemorrhage rate was 6%, and poor outcome rate was 66%. Variables associated with poor outcome were: age, baseline National Institutes of Health Stroke Scale, admission glucose, diabetes, heart disease, previous stroke, and the absence of mismatch on the pretreatment MRI. Logistic regression identified 3 variables independently associated with poor outcome: age ( P =0.049; OR, 1.028), National Institutes of Health Stroke Scale ( P =0.013; OR, 1.084), and admission glucose ( P =0.031; OR, 1.011). Using these data, we devised the Houston IAT score: 1 point for age >75 years; 1 for National Institutes of Health Stroke Scale score >18, and 1 point for glucose >150 mg/dL (range, 0 to 3 mg/dL). The percentage of poor outcome by Houston IAT score was: score of 0, 44%; 1, 67%; 2, 97%; and 3, 100%. Recanalization rates were similar across the scores ( P =0.4). Applying Houston IAT to the external cohort showed comparable trends in outcome and nearly identical rates in the Houston IAT therapy 3 tier. Conclusions— The Houston IAT score estimates the chances of poor outcome after IAT, even with recanalization. It may be useful in comparing cohorts of patients and when assessing the results of clinical trials.

Background: The drip-and-ship method of treating stroke patients may increase the use of tissue plasminogen activator (t-PA) in community hospitals. Objective: The safety and early outcomes of patients treated with t-PA for acute ischemic stroke (AIS) by the drip-and-ship method were compared to patients directly treated at a stroke center. Methods: The charts of all patients who were treated with intravenous (i.v.) t-PA at outside hospitals under the remote guidance of our stroke team and were then transferred to our facility were reviewed. Baseline NIHSS (National Institutes of Health Stroke Scale) scores, onset-to-treatment (OTT), and arrival-to-treatment (ATT) times were abstracted. The rates of in-hospital mortality, symptomatic hemorrhage (sICH), early excellent outcome (modified Rankin Scale [mRS] ≤ 1), and early good outcome (discharge home or to inpatient rehabilitation) were determined. Results: One hundred sixteen patients met inclusion criteria. Eighty-four (72.4%) were treated within 3 h of symptom onset. The median estimated NIHSS score was 9.5 (range 3–27). The median OTT time was 150 min, and the median ATT was 85 min. These patients had an in-hospital mortality rate of 10.7% and sICH rate of 6%. Thirty percent of patients had an early excellent outcome and 75% were discharged to home or inpatient rehabilitation. When these outcome rates were compared with those observed in patients treated directly at our stroke center, there were no statistical differences. Conclusions: In this small retrospective study, drip-and-ship management of delivering i.v. t-PA for AIS patients did not seem to compromise safety. However, a large prospective study comparing drip-and-ship management to routine care is needed to validate the safety of this approach to treatment.

Intraventricular extension of intracerebral hemorrhage (IVH) is an independent predictor of poor outcome. IVH volume may be important in outcome prediction and management; however, it is difficult to measure routinely.We reviewed the charts and computed tomographies of a cohort of consecutive patients with IVH. The cohort was divided into two groups: index and validation by random sampling. IVH and intracerebral hemorrhage (ICH) volume were measured manually in all patients. IVH was also graded using a simple classification system termed IVH score (IVHS). Clinical outcome was determined by the modified Rankin Scale (mRS) at discharge and in-hospital death. Poor outcome was defined as mRS 4-6.One hundred seventy-five patients were analyzed, 92 in the index group and 83 in the validation group. Exponential regression yielded the following formula for estimating IVH volume (mL): eIVHS/5 (R = .75, p0.001). The IVH estimation formula was then verified in the validation group (R = .8, p0.001). The following correlations with mRS were obtained: IVH volume R = .305; ICH volume R = .468; total volume [TV] R = .571 (p0.001 for all three correlations). Partial correlation of TV with mRS controlling for ICH volume yielded R = .3 for TV (p0.001). Logistic regression model comparing ICH and TV association with poor outcome yielded the following: ICH odds ratio = 5.2, 95% confidence interval 2.3-11.6, p0.001; TV odds ratio = 41.6, 95% confidence interval 9.6-180.6, p0.001. Substituting TV for ICH volume in the ICH score resulted in a significant increase in the specificity from 64% to 87% for predicting mortality.IVHS enables clinicians to rapidly estimate IVH volume. The addition of IVH to ICH volume increases its predictive power for poor outcome and mortality significantly. IVHS and TV may be used in clinical practice and clinical trials of patients with ICH.