Predictors and Prognostic Implications of Hemorrhagic Transformation Following Cerebral Endovascular Thrombectomy in Acute Ischemic Stroke: A Multicenter Analysis.

PURPOSE: Hemorrhagic transformation (HT) following cerebral endovascular thrombectomy (EVT) for large vessel occlusion (LVO) in acute ischemic stroke is associated with poor outcome. Recent studies have shown that EVT can be efficacious in imaging-selected patients as late as 6-24 h from onset (late time window; LTW). We sought to determine predictors and prognostic implications of HT following EVT in LTW. METHODS: Consecutive patients undergoing EVT for LVO were recruited into a prospective multicenter database. HT was divided into petechial hemorrhagic-infarction and parenchymal hematoma (PH) type 1 or 2 defined as confluent hemorrhage covering < or > than 1/3 of the infarct volume, respectively. Multivariate analyses were performed to determine variables associated with HT subtypes. RESULTS: Among 611 patients included (mean age 70.5 ± 12.5 years; median NIHSS 16), 115 (18.8%) had HT and 33 of them (5.4%) had PH2. Independent PH2 predictors included failed recanalization (OR 7.0, 95% CI 2.3-21.6), longer time from symptom onset to admission (OR 1.002 per minute 95% CI 1.001-1.003) and hyperlipidemia (OR 3.12; 95%CI 1.12-8.7). HT was not associated with outcome. In contrast, PH2 patients had lower favorable outcome rates (14.3 vs 41.6%, p = 0.004) and higher mortality rates (39 vs 17%, p = 0.001). Patients who underwent EVT in the late versus early window had similar PH2 rates (4.5 vs 6.7%, p = 0.27). In multivariate models, PH2 tripled the odds of both 90-day poor outcome (OR 3.1, 95% CI 1.01-9.5) and 90-day mortality (OR 3.2, 95% CI 1.4-7.3). CONCLUSIONS: PH2 following EVT is associated with increased mortality and unfavorable outcome rates. Rates of PH2 are not different between LTW patients and those treated < 6 h from symptom onset.

Cerebral microinfarcts disruption of remote cortical thickness.

INTRODUCTION: Cerebral microinfarcts (CMI) are common lesions, carrying an important contribution to small-vessel-related cognitive impairment. CMIs were previously found to cause local microstructural damage and disruption of white matter integrity. This study examines CMIs influence on cortical thickness in remote brain areas. METHODS: Six small silent diffuse weighted imaging (DWI) lesions corresponding to subacute CMI were identified among five patients who underwent baseline and follow-up MRI scans from the Tel-Aviv Acute Brain Stroke Cohort (TABASCO). Regions of interest (ROIs) corresponding to the site of the DWI lesions and of the non-lesioned contralateral hemisphere (control ROI) were co-registered. DTI tractography was additionally performed to reconstruct the white matter tracts containing the ROIs. The normalized cortical thickness was calculated for the DWI lesional tract as well as for the contralateral non-lesional tract, and the lesion-to-control cortical thickness ratio (CTR) was calculated. RESULTS: Post-lesional scans, performed 25.1 ± 1.2 months after CMI detection, demonstrated reduced mean CTR within the ROI from 1.8 to 1.1 (p = 0.032). There was no difference between the CTR of the right hemisphere relative to those on the left hemisphere, or between the CTR change of the cortical and non-cortical CMI. DISCUSSION: This study demonstrated the prolonged influence of CMI on cortical thickness in remote ROI. The total number of CMIs is difficult to determine, however it has been shown that detecting even a single CMI suggests the existence of hundreds to thousands lesions. Therefore, the cumulative impact of these widely distributed lesions on cerebral cortex may have a significant contribution to the development of vascular cognitive impairment.

Increased incidence of Susac syndrome: a case series study.

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.

Clinical and radiological determinants of transient symptoms associated with infarction (TSI).

BACKGROUND: The definition of transient ischemic attack was traditionally based on clinical features only. The wide use of magnetic resonance imaging (MRI) led to the definition of a new entity - transient symptoms associated with infarction (TSI). It is unclear why patients with similar radiological infarctions may have different clinical manifestation - ranging from complete symptoms resolution to major neurological sequelae. We sought to determine which factors differentiate acute diffuse weighted imaging (DWI) lesion presentation - stroke versus TSI. METHODS: 282 Participants, recruited for the Tel-Aviv Brain Acute Stroke Cohort study (TABASCO), were enrolled consecutively. Participants underwent extensive cognitive evaluation, wide laboratory tests and brain MRI scans evaluated for cerebral small vessel disease (SVD) biomarkers, according to the STRIVE protocol. Demographic and clinical characteristics were also examined. RESULTS: A total of 239 patients had stroke and 43 patients had TSI. TSI patients had smaller average lesion volume (0.77 cm3 versus 2.64 cm3, p = 0.002). Lesion location did not differentiate TSI and stroke. Stroke patients had elevated inflammatory markers, unrelated to lesion size (CRP 4.2 mg/L versus 1.7 mg/L, p = 0.011). TSI patients had better global cognitive score and MoCA score at admission and 24 months following the index event (p < 0.001). TSI patients also had better Berg balance score (p = 0.004). No significant association was found with MRI SVD markers. CONCLUSIONS: Lesion size, but not location, differentiates TSI and stroke, especially at a cutoff value of 10 cm3. Elevated inflammatory response was linked to worse course independently of lesion volume. Cognitive and high function tests are associated to the clinical phenotype of ischemic lesion and may be a marker of brain reserve and compensatory abilities. SVD markers do not differ between TSI and stroke patients and probably do not fully capture the extent of brain vascular pathology and reserve.

High hair cortisol concentrations predict worse cognitive outcome after stroke: Results from the TABASCO prospective cohort study.

BACKGROUND AND PURPOSE: The role of stress-related endocrine dysregulation in the development of cognitive changes following a stroke needs further elucidation. We explored this issue in a longitudinal study on stroke survivors using hair cortisol concentrations (HCC), a measure of integrated long-term cortisol levels. METHODS: Participants were consecutive cognitively intact first-ever mild-moderate ischemic stroke/transient ischemic attack (TIA) survivors from the Tel Aviv Brain Acute Stroke Cohort (TABASCO) study. They underwent 3T magnetic resonance imaging (MRI) scanning and were cognitively assessed at admission, and at 6, 12 and 24 months post-stroke. Scalp hair samples were obtained during the initial hospitalization. RESULTS: Full data on baseline HCC, MRI scans and 2 years neuropsychological assessments were available for 65 patients. Higher HCC were significantly associated with a larger lesion volume and with worse cognitive results 6, 12 and 24 months post-stroke on most of the neurocognitive tests. 15.4% of the participants went on to develop clinically significant cognitive decline in the follow-up period, and higher HCC at baseline were found to be a significant risk factor for this decline, after adjustment for age, gender, body mass index and APOE e4 carrier status (HR=6.553, p=0.038). CONCLUSIONS: Our findings suggest that individuals with higher HCC, which probably reflect higher long-term cortisol release, are prone to develop cognitive decline following an acute stroke or TIA.

Cognitive assessment in proximity to acute ischemic stroke/transient ischemic attack: comparison of the montreal cognitive assessment test and mindstreams computerized cognitive assessment battery.

BACKGROUND/AIMS: Even mild stroke survivors may sometimes experience residual cognitive damage. No consensus has emerged about which cognitive test is most appropriate for the diagnosis of poststroke cognitive impairment. We aim to compare a computerized battery of neuropsychological tests for memory, attention and executive functions (MindStreams®) with the Montreal Cognitive Assessment (MoCA) to detect mild-to-moderate cognitive impairments in poststroke patients. METHODS: Subjects enrolled to the TABASCO (Tel Aviv Brain Acute Stroke Cohort) study, a prospective study which includes consecutive first-ever mild-to-moderate stroke patients, were included. All participants underwent neurological and cognitive evaluations. RESULTS: A total of 454 patients with transient ischemic attack (TIA) or stroke are reported. Their mean MoCA and MindStreams scores were lower than normal; however, the TIA group presented significantly better scores using either method. The correlation between the MoCA and the computerized global score was 0.6 (p < 0.001). A significant correlation was found between the subcategory scores (executive function, memory and attention). However, the MoCA identified many more subjects with low scores (<26) compared to the MindStreams (70.6 vs. 15.7%). CONCLUSION: Our results demonstrate that either of the modalities alone is sensitive enough for identifying subtle cognitive impairment and none picks up substantially more cognitive losses than the other in patients with cerebrovascular disease.

Extra-cranial venous flow in patients with multiple sclerosis.

INTRODUCTION: Recently, a chronic state of impaired venous drainage from the central nervous system, termed chronic cerebrospinal venous insufficiency (CCSVI) was claimed to be a pathologic condition exclusively seen in patients with multiple sclerosis (MS), suggesting that cerebral venous congestion plays a significant role in the pathogenesis of MS. This hypothesis has gained enormous attention among patients and physicians but has been questioned since. METHODS: Twenty seven patients with MS and 32 healthy controls underwent color extra cranial Doppler exam aimed to detect four parameters of abnormal venous flow: no Doppler-detected flow in the IJV or vertebral veins (VV), reflux in the internal jugular veins (IJVs), venous flow stenosis in the IJVz (cross sectional area <0.3 cm) or reverted postural control in the IJV. RESULTS: Except for one healthy patient, blood flow direction in the IJVs was normal in all subjects. When aiming to detect at least one parameter of abnormal venous flow per subject, two parameters or three parameters no significant difference was found between subjects and controls (p = 0.707, 0.62, 0.849 respectively). CONCLUSION: We found no evidence to suggest that MS patients have excess of CCSVI. In addition we failed to observe a typical venous flow pattern in MS patients. Until carefully designed controlled studies to investigate CCVSI have been completed, invasive and potentially dangerous endovascular procedures as therapy for MS should be discouraged.

Prior antiplatelet therapy and outcome following intracerebral hemorrhage: a systematic review.

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.

Intraventricular hemorrhage: Anatomic relationships and clinical implications.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is frequently associated with intraventricular hemorrhage (IVH), which is an independent predictor of poor outcome. The purpose of this study was to examine the relationship between ICH volume and anatomic location to IVH, and to determine if ICH decompression into the ventricle is truly beneficial. METHODS: We retrospectively analyzed the CT scans and charts of all patients with ICH admitted to our stroke center over a 3-year period. Outcome data were collected using our prospective stroke registry. RESULTS: We identified 406 patients with ICH. A total of 45% had IVH. Thalamic and caudate locations had the highest IVH frequency (69% and 100%). ICH volume and ICH location were predictors of IVH (p < 0.001). Within each location, decompression ranges (specific volume ranges where ventricular rupture tends to occur) were established. Patients with IVH were twice as likely to have a poor outcome (discharge modified Rankin scale of 4 to 6) (OR 2.25, p = 0.001) when compared to patients without IVH. Caudate location was associated with a good outcome despite 100% incidence of IVH. Spontaneous ventricular decompression was not associated with better outcome, regardless of parenchymal volume reduction (p = 0.72). CONCLUSIONS: Intraventricular hemorrhage (IVH) occurs in nearly half of patients with spontaneous intracerebral hemorrhage (ICH) and is related to ICH volume and location. IVH is likely to occur within the "decompression ranges" that take into account both ICH location and volume. Further, spontaneous ventricular decompression does not translate to better clinical outcome. This information may prove useful for future ICH trials, and to the clinician communicating with patients and families.

Modification of neutrophil adhesion to human endothelial cell line in acute ischemic stroke by dipyridamole and candesartan.

Ischemic stroke is a leading cause of disability. Inflammation of the vessel wall following neutrophil adhesion to vascular endothelium may contribute to ischemic damage. We studied the effect of a platelet inhibitor and an angiotensin II receptor antagonist: alone or in combination, on the adhesion of neutrophils to endothelial cell line in stroke patients. Neutrophils were collected from 12 patients with ischemic stroke within 48 h. Six patients with previous stroke and six healthy volunteers served as control. Neutrophils were incubated with dipyridamole, candesartan or both and allowed to adhere to human endothelial cell line (ECV-304). Adhesion and expression of adhesion molecules (AM) were determined using fluorescence-activated cell-sorting (FACS). Dipyridamole and the combination of dipyridamole and candesartan inhibited significantly the adhesion of neutrophils from ischemic stroke patients as compared to controls with a prominent additive effect. No inhibition was seen in the control groups. These drugs also reduced significantly the expression of the AM Mac-1. Both candesartan and dipyridamole inhibited the adhesion of neutrophils to vascular endothelium in ischemic stroke patients but not in chronic stroke patients or healthy persons. This effect may be related to specific downregulation of Mac-1 by these drugs or other intracellular events.