Jeremy Molad

Only White Matter Hyperintensities Predicts Post-Stroke Cognitive Performances Among Cerebral Small Vessel Disease Markers: Results from the TABASCO Study

BACKGROUND White matter hyperintensities (WMH) were shown to predict cognitive decline following stroke or transient ischemic attack (TIA). However, WMH are only one among other radiological markers of cerebral small vessel disease (SVD). OBJECTIVE The aim of this study was to determine whether adding other SVD markers to WMH improves prediction of post-stroke cognitive performances. METHODS Consecutive first-ever stroke or TIA patients (n = 266) from the Tel Aviv Acute Brain Stroke Cohort (TABASCO) study were enrolled. MRI scans were performed within seven days of stroke onset. We evaluated the relationship between cognitive performances one year following stroke, and previously suggested total SVD burden score including WMH, lacunes, cerebral microbleeds (CMB), and perivascular spaces (PVS). RESULTS Significant negative associations were found between WMH and cognition (p < 0.05). Adding other SVD markers (lacunes, CMB, PVS) to WMH did not improve predication of post-stroke cognitive performances. Negative correlations between SVD burden score and cognitive scores were observed for global cognitive, memory, and visual spatial scores (all p < 0.05). However, following an adjustment for confounders, no associations remained significant. CONCLUSION WMH score was associated with poor post-stroke cognitive performance. Adding other SVD markers or SVD burden score, however, did not improve prediction.

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.

Impaired renal function is associated with brain atrophy and poststroke cognitive decline

Objective: To evaluate the interrelationship among impaired renal function, brain pathology on imaging, and cognitive decline in a longitudinal poststroke cohort. Methods: The Tel Aviv Brain Acute Stroke Cohort study is a prospective cohort of mild-moderate ischemic stroke/TIA survivors without dementia who underwent a 3T MRI and were cognitively assessed at admission and for 24 months following stroke. Renal function was evaluated at admission by creatinine clearance (CCl) estimation. The volumes of ischemic lesions and preexisting white matter hyperintensities (WMH), brain atrophy, and microstructural changes of the normal-appearing white matter tissue were measured using previously validated methods. Results: Baseline data were available for 431 participants. Participants with a CCl <60 mL/min at baseline performed significantly worse in all cognitive tests over time (p = 0.001) than those with a CCl ≥60 mL/min and had larger WMH volume and cortical atrophy and smaller hippocampal volume (all p < 0.001). After 2 years, 15.5% of the participants were diagnosed with cognitive impairment. Multiple logistic regression analysis, controlling for traditional risk factors, suggested CCl <60 mL/min at baseline as a significant predictor for the development of cognitive impairment 2 years after the index stroke (odds ratio 2.01 [95% confidence interval 1.03–3.92], p = 0.041). Conclusions: Impaired renal function is associated with increased WMH volume and cortical atrophy, known biomarkers of the aging brain, and is a predictor for cognitive decline 2 years after stroke/TIA. Decreased renal function may be associated with cerebral small vessel disease underlying poststroke cognitive decline, suggesting a new target for early intervention.

Association of statin use with spontaneous intracerebral hemorrhage: A cohort study

Objective To examine the association between statin exposure in a dose-dependent manner and intracerebral hemorrhage (ICH) in a large nationwide study. Methods The computerized database of the largest health care provider in Israel was used to identify diagnosed ICH among new users of statins, who started statin treatment between 2005 and 2010. We assessed a dose–response relationship between ICH and statins, using the average atorvastatin equivalent daily dose (AAEDD). Multivariable Cox proportional hazard regression models, adjusted for baseline disease risk score, were applied to estimate the hazard ratio of ICH. Results Of the 345,531 included patients, 1,304 were diagnosed with ICH during a median follow-up of 9.5 years (interquartile range 7.6–11.0). Overall, 75.3% of patients had AAEDD <10 mg/d, 19.0% had AAEDD 0–19.9 mg/d, and 5.7% had AAEDD ≥20 mg/d. The corresponding proportions were 81.0%, 15.0%, 4.0% among ICH cases, and 75.3%, 19.0%, 5.7% among non-ICH cases. Compared to those with AAEDD <10 mg/d (reference), the adjusted hazard ratio (HR) for ICH was 0.68 (95% confidence interval [CI] 0.58–0.79) in those with AAEDD 10–19.9 mg/d, and 0.62 (0.47–0.81) in those with AAEDD ≥20 mg/d. Compared to the lowest baseline total cholesterol quartile, the adjusted HR for ICH was 0.71 (95% CI 0.62–0.82), 0.55 (0.47–0.64), and 0.57 (0.49–0.67) in those in the second, third, and highest quartiles, respectively. The results were similar and robust among highly persistent statin users and after controlling for the change in cholesterol level. Conclusions This study confirms that the risk of ICH decreases with increasing cholesterol levels, but suggests that statin use might be associated with decreased risk of ICH.

Type 2 Diabetes Mellitus and Impaired Renal Function Are Associated With Brain Alterations and Poststroke Cognitive Decline.

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] <60 mL/min) were associated with smaller brain and hippocampal volumes, reduced cortical thickness, and worse white matter microstructural integrity. Two years later, both T2DM and eCCl <60 mL/min were associated with poorer cognitive scores, and 19.7% of the participants developed cognitive decline (mild cognitive impairment or dementia). Multiple analysis, controlling for age, sex, education, and apolipoprotein E4, showed a significant association of both T2DM and eCCl <60 mL/min with cognitive decline. Having both conditions doubled the risk compared with patients with T2DM or eCCl <60 mL/min alone and almost quadrupled the risk compared with patients without either abnormality. 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.

Computed Tomography Perfusion-Based Decision Making for Acute Ischemic Stroke—Missing the Mismatch

The emerging use of mechanical thrombectomy for acute ischemic stroke treatment focuses on the importance of patient selection. Computed tomography perfusion (CTP) is one of widely used techniques. However, the accuracy and reliability of this modality is in debate among vascular neurologists. We present a case of an 80-year-old man admitted because of acute ischemic stroke. CT angiography demonstrated left proximal M2 occlusion. As CTP demonstrated signs of large ischemic core with no significant penumbra, mechanical thrombectomy was not performed following tPA administration. Twenty-four hours after thrombolysis, the patient was neurologically intact. Both non-contrast CT and magnetic resonance imaging (MRI) demonstrated small stroke involving the left caudate. Differences between CTP and MRI diffuse-weighted imaging were previously described. However, in the presented case, these differences were brought to extreme, precluding endovascular treatment. In our opinion, this case emphasizes why CTP should not be used for patient exclusion among patients in the early time frame for intervention. Such patients should be evaluated by MRI or by clinical-radiological mismatch only. CTP may have a role in selecting patients for endovascular intervention in borderline circumstances such as prolonged time window, wake-up stroke, etc.

Abstract TMP92: Keep On Working. Occupational Status Before and After Stroke Protects the Brain, General Health and Cognitive Status

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 interrela...

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.

Symptomatogenic acute cervical artery dissection following dental procedure — Case series

INTRODUCTION Cervical artery dissection (CAD) is an important cause of ischemic stroke which may occur following minor traumatic neck manipulations or hyperextension. This paper describes four cases of CAD secondary to dental procedures. CASES Four patients were admitted to the neurology department due to various neurological deficits, which developed subsequently to dental procedure. CT angiography demonstrated CAD in all patients. No predisposing background disease or other neck manipulations were found. DISCUSSION We describe four cases of dental procedure induced CAD. Since dental procedures are very common, CAD incidence may be higher than recognized. High clinical suspicion is crucial for promoting vascular imaging and diagnosis, especially among patients with non-neurologically symptomatic CAD. We suggest avoiding prolonged neck hyperextension during dental procedures, especially under general anesthesia, in order to prevent this rare but dramatic complication.