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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.

Few data describing pre-diagnosis changes in patients with inflammatory bowel disease (IBD) exist. We aimed to determine if there is a pattern of change in use of health resources, medications and laboratory results in the years preceding diagnosis.This retrospective study used electronic medical records of Maccabi Health Services (MHS). Patients with IBD ≥ 16 years of age and minimum of 5-years follow-up were identified by entry into the MHS IBD registry and included in the analysis. Demographic, clinical, medication and laboratory data were collected. Generalized estimating equation model was applied to study trends and compare between years.This study included 5643 patients with IBD. Of these, 3039 (53.8%) had Crohn's disease (CD), 2322 (41.1%) had ulcerative colitis (UC) and 282 (5%) had indeterminate colitis (IC). Laboratory parameters including white blood cells, platelets and C-reactive protein showed significant increases while haemoglobin and mean cell volume showed significant decreases in mean values in the 2 years prior to diagnosis with stable values prior to that (p 0.0001). Parameters such as creatinine, total protein and albumin showed significant, progressive decreases in mean values starting 5 years prior to diagnosis (p 0.0001). Patients with CD had distinct laboratory trends when compared with patients with UC.Changes in laboratory parameters, healthcare service and medication use occur during the 5-year period before IBD diagnosis. These data can have future clinical applicability by developing a composite score and referral algorithm introducing red flags into primary care visits and appropriate referral for specialist care.

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 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 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 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.

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.

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.

To evaluate the interrelationship among impaired renal function, brain pathology on imaging, and cognitive decline in a longitudinal poststroke cohort.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.Baseline data were available for 431 participants. Participants with a CCl60 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 p0.001). After 2 years, 15.5% of the participants were diagnosed with cognitive impairment. Multiple logistic regression analysis, controlling for traditional risk factors, suggested CCl60 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).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.

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.

Cerebral atrophy has been detected in patients with Parkinson’s disease (PD) both with and without dementia, however differentiation based on genetic status has thus far not yielded robust findings. We assessed cortical thickness and subcortical volumes in a cohort of PD patients and healthy controls carriers of the G2019S mutation in the LRRK2 gene and the common GBA mutations, in an attempt to determine whether genetic status influences structural indexes. Cortical thickness and subcortical volumes were computed and compared between six groups of participants; idiopathic PD, GBA-PD, LRRK2-PD, non-manifesting non-carriers (NMNC), GBA-non-manifesting carriers (NMC) and LRRK2-NMC utilizing the FreeSurfer software program. All participants were cognitively intact based on a computerized cognitive assessment battery. Fifty-seven idiopathic PD patients, 9 LRRK2-PD, 12 GBA-PD, 49 NMNC, 41 LRRK2-NMC and 14 GBA-NMC participated in this study. Lower volumes among patients with PD compared to unaffected participants were detected in bilateral hippocampus, nucleus accumbens, caudate, thalamus, putamen and amygdala and the right pallidum (p = 0.016). PD patients demonstrated lower cortical thickness indexes in a majority of regions assessed compared with non-manifesting participants. No differences in cortical thickness and subcortical volumes were detected within each of the groups of participants based on genetic status. Mutations in the GBA and LRRK2 genes are not important determinants of cortical thickness and subcortical volumes in both patients with PD and non-manifesting participants. PD is associated with a general reduction in cortical thickness and sub-cortical atrophy even in cognitively intact patients.

We tested a newly described molecular memory system, CCR5 signaling, for its role in recovery after stroke and traumatic brain injury (TBI). CCR5 is uniquely expressed in cortical neurons after stroke. Post-stroke neuronal knockdown of CCR5 in pre-motor cortex leads to early recovery of motor control. Recovery is associated with preservation of dendritic spines, new patterns of cortical projections to contralateral pre-motor cortex, and upregulation of CREB and DLK signaling. Administration of a clinically utilized FDA-approved CCR5 antagonist, devised for HIV treatment, produces similar effects on motor recovery post stroke and cognitive decline post TBI. Finally, in a large clinical cohort of stroke patients, carriers for a naturally occurring loss-of-function mutation in CCR5 (CCR5-Δ32) exhibited greater recovery of neurological impairments and cognitive function. In summary, CCR5 is a translational target for neural repair in stroke and TBI and the first reported gene associated with enhanced recovery in human stroke.

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.

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.

Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is a disorder of unknown etiology, predominantly affecting obese women of childbearing age. IIH is uncommon in men, with a reported female-to-male ratio of 8:1. The pathogenesis of IIH is poorly understood. Several mechanisms have been suggested, but no one mechanism has been able to account for all manifestations of the disease. This research aims to characterize the obesity phenotype(s) of men with IIH in order to find potential inducers for this disease.This is a cross-sectional study based on subjects' medical records. It compared anthropometric parameters between 22 men with IIH, 60 healthy men, and 44 females with IIH. One-way analysis with age and body mass index included as covariates was applied for the assessment of the difference in fat distribution among the three groups.No significant differences were observed between the male IIH cohort and healthy males for age, BMI, and waist measurements, whereas hip circumference was significantly larger in the IIH cohort (114 ± 13 vs. 104 ± 16 cm; respectively, p0.001). Consequently, waist-to-hip ratio (WHR) was significantly lower in the male IIH cohort (0.88 ± 0.08 vs. 0.95 ± 0.12; p0.001). While no significant differences were observed for age and hip measurements between male IIH and female IIH cohorts, waist circumference and waist-to-hip ratio (WHR) were significantly larger in the male cohort (102 ± 19 cm vs. 95 ± 13 cm, p0.001; 0.88 ± 0.08 vs. 0.78 ± 0.06, p0.001, respectively). All these results maintained after adjustment for age and BMI.This is the first report of body fat distribution patterns in men with IIH. Whereas male IIH have larger central fat deposition than female IIH patients, abdominal fatness is less accentuated in IIH men compared to normal obese men. The later observation is in agreement with similar results regarding female IIH patients. We believe that these findings justify further investigation into the involvement of various fat depots in the pathogenesis of IIH in men and women alike.

Purpose: Previous reports have connected between Idiopathic intracranial hypertension (IIH), obesity and different hormonal states. The aim of this study was to characterize the endocrine profile in women with IIH. Methods: This is a data-based study of 51 IIH patients. We measured anthropometric parameters and assessed hormonal profile including cortisol, testosterone, bioavailable testosterone (BT), prolactin, dehydroepiandrosterone sulfate (DHEA-S), androstenedione, insulin, aldosterone, estradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Pearson or Spearman rank correlation for non-normally distributed variables were calculated to evaluate the relation among the anthropometric measurements: age, body mass index (BMI), waist and hip circumference and waist to hip ratio (WHR) with hormones levels. Results: Seventy-eight percent of the cohort had WHR50.85 and 21.6% had a WHR40.85. Increased levels of testosterone, BT and androstenedione were all positively related to younger age of diagnosis in patient who are diagnosed after the age of 25 (R =1.066, 0.845, 0.735, p50.001, =0.024, 0.019, respectively). No correlation was found between any of the analyzed hormones and the duration of the disease, WHR or BMI, except insulin, which was positively related to BMI (R = 0.461, p = 0.001). Conclusions: Increased levels of circulating androgens are associated with earlier age of onset of IIH in women.

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

Contains fulltext : 170402.pdf (Publisher’s version ) (Open Access) Post-stroke dementia (PSD) or post-stroke cognitive impairment (PSCI) may affect up to one third of stroke survivors. Various definitions of PSCI and PSD have been described. We propose PSD as a label for any dementia following stroke in temporal relation. Various tools are available to screen and assess cognition, with few PSD-specific instruments. Choice will depend on purpose of assessment, with differing instruments needed for brief screening (e.g., Montreal Cognitive Assessment) or diagnostic formulation (e.g., NINDS VCI battery). A comprehensive evaluation should include assessment of pre-stroke cognition (e.g., using Informant Questionnaire for Cognitive Decline in the Elderly), mood (e.g., using Hospital Anxiety and Depression Scale), and functional consequences of cognitive impairments (e.g., using modified Rankin Scale). A large number of biomarkers for PSD, including indicators for genetic polymorphisms, biomarkers in the cerebrospinal fluid and in the serum, inflammatory mediators, and peripheral microRNA profiles have been proposed. Currently, no specific biomarkers have been proven to robustly discriminate vulnerable patients ('at risk brains') from those with better prognosis or to discriminate Alzheimer's disease dementia from PSD. Further, neuroimaging is an important diagnostic tool in PSD. The role of computerized tomography is limited to demonstrating type and location of the underlying primary lesion and indicating atrophy and severe white matter changes. Magnetic resonance imaging is the key neuroimaging modality and has high sensitivity and specificity for detecting pathological changes, including small vessel disease. Advanced multi-modal imaging includes diffusion tensor imaging for fiber tracking, by which changes in networks can be detected. Quantitative imaging of cerebral blood flow and metabolism by positron emission tomography can differentiate between vascular dementia and degenerative dementia and show the interaction between vascular and metabolic changes. Additionally, inflammatory changes after ischemia in the brain can be detected, which may play a role together with amyloid deposition in the development of PSD. Prevention of PSD can be achieved by prevention of stroke. As treatment strategies to inhibit the development and mitigate the course of PSD, lowering of blood pressure, statins, neuroprotective drugs, and anti-inflammatory agents have all been studied without convincing evidence of efficacy. Lifestyle interventions, physical activity, and cognitive training have been recently tested, but large controlled trials are still missing.

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.

Several studies have suggested that thrombophilic risk factors are more prevalent in individuals with idiopathic intracranial hypertension (IIH), and that a prothrombic state may be involved in the etiopathogenesis of this disease. We examine thrombophilic factors in a group of patients with IIH in relation to obesity. In addition, we reviewed the relevant literature and performed a meta-analysis. Thrombophilia work-up was performed on 51 patients with IIH at least 1 month following their first episode. Samples for the analysis of factor V Leiden (FVL), prothrombin gene variant (PGV) G20210A and methylenetetrahydrofolate reductase (MTHFR) were available in an additional 30 patients, that is 81 patients in all. Meta-analysis was performed. Of the 51 patients 40 were obese. Increased concentrations of fibrinogen, D-Dimer, factor VIII, factor IX and factor XI were found in 15, 7, 7, 6 and 2 patients, respectively, all obese. The circulating anticoagulant, measured by dilute Russell's viper venom time (dRVVT assay), found mainly in obese. All 51 patients were negative for the anticardiolipin antibody (IgG immunoglobulin G) and IgG anti-beta2 glycoprotein I. In the meta-analysis antiphospholipid antibodies were significantly associated with IIH [odds ratio (OR) of 4.25 (1.68-12.60)], similar to the association with high factor VIII [OR = 16.17 (2.87-91.01)], higher plasminogen activator inhibitor-1 (PAI-1) levels [OR = 6.91 (2.28-20.91)], and high lipoprotein (a) [LP(a)] [OR = 3.54 (1.54-8.70)]. Obesity often observed in IIH patients is frequently linked with thrombophilic factors. Thus, we believe that dysmetabolism could be the thrombophilic target for treatment in patients with IIH.

To characterize the obesity phenotype(s) in patients with idiopathic intracranial hypertension (IIH).Database study.We studied 44 consecutive patients with IIH, in addition to 184 women attending the obesity clinic of the same medical center and 199 obese women participating in the first Israeli national survey on health and nutrition conducted in 1999 and 2000.Anthropometric parameters were compared with those of 2 control groups of the same age range.Weight, height, and waist and hip circumference were measured.Forty subjects, comprising 91.0% of this cohort, were either overweight (body mass index, 25.0-29.9 kg/m(2)) or obese (body mass indexor = 30 kg/m2). Mean waist circumference was 95.3 cm for IIH, 99.8 cm for the national survey, and 114.5 cm for the obesity clinic cohort (P0.001), whereas hip circumference was 121 cm for IIH, 118.4 cm for the national survey, and 125.8 cm (P = not significant) for the obesity clinic cohorts. Waist-to-hip ratio, a descriptive measure of body fat distribution approximately reflecting upper to lower body fat ratio, was 0.79 in the patients with IIH, 0.84 in the national survey group, and 0.91 in the obesity clinic cohort (P0.001; all comparisons were adjusted for age and body mass index).In IIH, fat tends to preferentially accumulate in the lower body relative to other obese women of the same range. Whereas most complications of obesity, such as hypertension, diabetes, dyslipidemia, and the metabolic syndrome, are linked to upper body adiposity, IIH may represent a unique condition potentially induced by nonvisceral fat-related mechanisms.The authors have no proprietary or commercial interest in any materials discussed in this article.

Introduction: Post-stroke patients are at high risk of developing cognitive decline. Previous studies have examined only limited magnetic resonance imaging (MRI) parameters for prediction of cognitive status following stroke Aim: To determine radiological markers associated with different cognitive domains in post-stroke patients. Materials and Methods: Patients from the TABASCO (Tel-Aviv Brain Acute Stroke Cohort), a prospective cohort of first-ever mild-moderate ischemic stroke patients, were Included (N=141). All patients underwent a 3T MRI and were cognitively assessed at admission and 2 later. Multiple regression models were used to assess which of the imaging measures best associated with cognitive scores 2 years after the index event. Results: After controlling for both age and education, the comparisons between cognitively intact and impaired patients revealed significant differences between the two groups in relative CSF volume, white matter lesion (WML) load and white matter microstructural integrity, reflected as mean diffusivity (MD), radial diffusivity (Dr) and axial diffusivity (Da) values ( p’s Discussion: Our results highlight the role of hippocampal MD and WML load as markers for cognitive performances. We suggest that these imaging markers best demonstrated "brain intergrity"

Trauma causes variable risk of posttraumatic stress symptoms (PTSS) owing to yet-unknown genome–neuronal interactions. Here, we report co-intensified amygdala and ventromedial prefrontal cortex (vmPFC) emotional responses that may overcome PTSS in individuals with the single-nucleotide polymorphism (SNP) rs17228616 in the acetylcholinesterase (AChE) gene. We have recently shown that in individuals with the minor rs17228616 allele, this SNP interrupts AChE suppression by microRNA (miRNA)-608, leading to cortical elevation of brain AChE and reduced cortisol and the miRNA-608 target GABAergic modulator CDC42, all stress-associated. To examine whether this SNP has effects on PTSS and threat-related brain circuits, we exposed 76 healthy Israel Defense Forces soldiers who experienced chronic military stress to a functional magnetic resonance imaging task of emotional and neutral visual stimuli. Minor allele individuals predictably reacted to emotional stimuli by hyperactivated amygdala, a hallmark of PTSS and a predisposing factor of posttraumatic stress disorder (PTSD). Despite this, minor allele individuals showed no difference in PTSS levels. Mediation analyses indicated that the potentiated amygdala reactivity in minor allele soldiers promoted enhanced vmPFC recruitment that was associated with their limited PTSS. Furthermore, we found interrelated expression levels of several miRNA-608 targets including CD44, CDC42 and interleukin 6 in human amygdala samples (N=7). Our findings suggest that miRNA-608/AChE interaction is involved in the threat circuitry and PTSS and support a model where greater vmPFC regulatory activity compensates for amygdala hyperactivation in minor allele individuals to neutralize their PTSS susceptibility.

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 0.005), and with cognitive state 6 and 12 months after the event. Multiple regression analyses demonstrated the predictive role of hippocampal mean diffusivity (β = -0.382, P = 0.026) on cognitive state, above and beyond that of volume and connectivity of this structure. To our knowledge, the combination of hippocampal volume, mean diffusivity and connectivity in first ever post stroke or TIA patients has not yet been considered in relation to cognitive state. The results demonstrate the predictive role of hippocampal mean diffusivity, suggesting that these changes may precede and contribute to volumetric and connectivity changes in the hippocampi, potentially serving as a marker for early identification of patients at risk of developing cognitive impairment or dementia.

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.

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