Nilufer Yesilot

Interleukin-6 in neuro-Behçet's disease: association with disease subsets and long-term outcome.

Increased cerebrospinal fluid (CSF) IL-6 has been reported in patients with Behçets disease (BD) and neurological involvement. To elucidate the value of IL-6 as a marker of disease activity, serum and CSF IL-6 levels of 68 BD patients with acute (26) or chronic progressive (14) parenchymal involvement (pNB), dural sinus thrombosis (10), ischemic stroke (5) or headache (13) were measured by ELISA. Samples from multiple sclerosis, subacute sclerosing panencephalitis, and noninflammatory neurological disorders were used as controls. CSF but not serum samples of neuro-BD patients with acute pNB displayed significantly increased IL-6 levels as compared to other groups. Chronic progressive pNB patients also showed increased CSF IL-6 levels, albeit less prominent. Patients with increased CSF IL-6 levels were more likely to have increased CSF cell counts and total protein levels and these three parameters were correlated with long-term (3 years) disease outcome. In four chronic progressive patients, IL-6 was elevated despite otherwise normal CSF. CSF IL-6 seems to be a marker of disease activity and long-term outcome for pNB along with CSF cell count and protein levels. CSF IL-6 could be used in chronic progressive patients who have normal CSF cell, or protein levels to detect disease activity.

Demographic and geographic vascular risk factor differences in european young adults with ischemic stroke: The 15 cities young stroke study

Background and Purpose— We compared among young patients with ischemic stroke the distribution of vascular risk factors among sex, age groups, and 3 distinct geographic regions in Europe. Methods— We included patients with first-ever ischemic stroke aged 15 to 49 years from existing hospital- or population-based prospective or consecutive young stroke registries involving 15 cities in 12 countries. Geographic regions were defined as northern (Finland, Norway), central (Austria, Belgium, France, Germany, Hungary, The Netherlands, Switzerland), and southern (Greece, Italy, Turkey) Europe. Hierarchical regression models were used for comparisons. Results— In the study cohort (n=3944), the 3 most frequent risk factors were current smoking (48.7%), dyslipidemia (45.8%), and hypertension (35.9%). Compared with central (n=1868; median age, 43 years) and northern (n=1330; median age, 44 years) European patients, southern Europeans (n=746; median age, 41 years) were younger. No sex difference emerged between the regions, male:female ratio being 0.7 in those aged <34 years and reaching 1.7 in those aged 45 to 49 years. After accounting for confounders, no risk-factor differences emerged at the region level. Compared with females, males were older and they more frequently had dyslipidemia or coronary heart disease, or were smokers, irrespective of region. In both sexes, prevalence of family history of stroke, dyslipidemia, smoking, hypertension, diabetes mellitus, coronary heart disease, peripheral arterial disease, and atrial fibrillation positively correlated with age across all regions. Conclusions— Primary preventive strategies for ischemic stroke in young adults—having high rate of modifiable risk factors—should be targeted according to sex and age at continental level.

Gender differences in acute stroke: Istanbul medical school stroke registry.

BACKGROUND We aimed to investigate gender differences in Turkish stroke patients. MATERIAL AND METHODS Demographics, risk factors, clinical and etiologic subtypes, laboratory findings, clinical course, and in-hospital prognosis of 1 522 patients with ischemic stroke (IS) and 320 patients with intracerebral hemorrhage prospectively registered in the Istanbul Medical School Stroke Registry (1994-2004) were analyzed separately. RESULTS The mean age of IS patients was higher in females (n : 751) (P<0.0001). In males, smoking, ischemic heart disease, peripheral arterial disease, posterior circulation syndromes, and strokes due to large-artery atherosclerosis were more common (P<0.0001 for each). Prestroke disability, atrial fibrillation (P<0.0001), hypertension (P=0.041), modified Rankin Scale (mRS) 3-5 at admission (P<0.0001), total anterior circulation syndrome (P<0.0001), and cardioembolic stroke (P<0.0001) were more frequent in females. Female gender was an independent predictor of poor outcome (mRS 3-6). CONCLUSION Gender differences were observed exclusively in patients with IS. Although our patients were younger than those reported, gender differences were similar.

A Multicenter Study of 1144 Patients with Cerebral Venous Thrombosis: The VENOST Study

BACKGROUND Based on a number of small observational studies, cerebral venous sinus thrombosis has diverse clinical and imaging features, risk factors, and variable outcome. In a large, multicenter cerebral venous thrombosis (VENOST) study, we sought to more precisely characterize the clinical characteristics of Caucasian patients. METHODS All data for the VENOST study were collected between the years 2000 and 2015 from the clinical follow-up files. Clinical and radiological characteristics, risk factors, and outcomes were compared in terms of age and sex distribution. RESULTS Among 1144 patients 68% were women, and in older age group (>50 years) male patients were more prevalent (16.6% versus 27.8%). The most frequent symptoms were headache (89.4%) and visual field defects (28.9%) in men, and headache (86.1%) and epileptic seizures (26.8%) in women. Gynecological factors comprised the largest group in women, in particular puerperium (18.3%). Prothrombotic conditions (26.4%), mainly methylenetetrahydrofolate reductase mutation (6.3%) and Factor V Leiden mutation (5.1%), were the most common etiologies in both genders. 8.1% of patients had infection-associated and 5.2% had malignancy-related etiology that was significantly higher in men and older age group. Parenchymal involvement constitutively hemorrhagic infarcts, malignancy, and older age was associated with higher Rankin score. Epileptic seizures had no effect on prognosis. CONCLUSIONS Clinical and radiological findings were consistent with previous larger studies but predisposing factors were different with a higher incidence of puerperium. Oral contraceptive use was not a prevalent risk factor in our cohort. Malignancy, older age, and hemorrhagic infarcts had worse outcome.

A Case Report of Cerebral Venous Thrombosis in Polycythemia Vera Presenting with Intracranial and Spinal Subdural Hematoma.

Spinal subdural hematoma (SDH) is a rare condition and can be caused by several factors. Concomitant cranial and spinal SDH is even much less common. We present a 77-year-old male patient with lower back pain, paraparesis, and urinary retention following a sudden onset headache. Imaging revealed concomitant cranial and spinal SDH related to cerebral venous thrombosis (CVT) associated with hemorrhagic venous infarct. Laboratory examinations were consistent with polycythemia vera. There was no history of trauma and previous cranial surgery. Brain angiography did not reveal any evidence of arteriovenous fistula or vascular malformation. Since lower back pain occurred shortly after the headache and there was no other reasonable explanation for spinal hemorrhage, we suppose that the mechanism of spinal SDH is the migration of blood from the intracranial compartment. Therefore, this is the first report of concomitant spinal SDH and cerebral hemorrhage associated with CVT in a patient with myeloproliferative disease.

Glycoprotein Ib-alpha Kozak polymorphism in ischemic stroke.

Abstract Background: Recently, a T/C polymorphism in the Kozak sequence of glycoprotein Ib-alpha (GPIb-alpha) gene at position −5 from the initiator ATG codons, has been identified. The presence of −5C allele increases the surface expression of GPIb-IX–V complex in a gene dosage-dependent manner. It has been suggested that higher receptor levels might increase the adhesiveness of the platelets and confer risk for thrombosis. In this study, we aimed to investigate the association between GPIb-alpha Kozak polymorphism and ischemic stroke. Methods: We prospectively and consecutively recruited 231 patients (118 women and 113 men; mean age: 65±14·2 years) with first ever ischemic stroke admitted to Istanbul Faculty of Medicine Edip Aktin Stroke Unit between April 2007 and June 2009. Demographic features, risk factors, clinical, and etiological subtypes were analyzed. As the control group, 220 unrelated healthy subjects were included. Results: We found that 156 patients had TT, 70 patients had TC, and 5 patients had CC genotype. At least one copy of C allele carriers were overrepresented in the ischemic stroke group (32·5%) compared with controls (23%) [odds ratio (OR): 0·61; 95% confidence interval (CI): 0·40–0·93; P = 0·03]. Among etiologic subtypes, the distribution of C allele carriers was the highest in patients with undetermined etiology (45%) and it was significantly higher than controls (OR: 0·36; 95% CI: 0·20–0·65; P = 0·0008). In other subtypes, there was no association with Kozak −5C allele. Conclusion: In conclusion, these encouraging preliminary results show that GPIb-alpha T/C polymorphism might increase the risk of ischemic stroke, especially in those with undetermined etiology.

Behçet’s disease as a causative factor of cerebral venous sinus thrombosis: subgroup analysis of data from the VENOST study

OBJECTIVE This study was performed to determine the rate of cerebral venous sinus thrombosis (CVST) among cases of Behçets disease (BD) included in a multicentre study of cerebral venous sinus thrombosis (VENOST). METHODS VENOST was a retrospective and prospective national multicentre observational study that included 1144 patients with CVST. The patients were classified according to aetiologic factors, time of CVST symptom onset, sinus involvement, treatment approach and prognosis. RESULTS BD was shown to be a causative factor of CVST in 108 (9.4%) of 1144 patients. The mean age of patients in the BD group was 35.27 years and 68.5% were men, whereas in the non-BD CVST group, the mean age was 40.57 years and 28.3% were men (P < 0.001). Among the aetiologic factors for patients aged 18-36 years, BD was predominant for men, and puerperium was predominant for women. The onset of symptoms in the BD group was consistent with the subacute form. The transverse sinuses were the most common sites of thrombosis, followed by the superior sagittal sinuses. The most common symptom was headache (96.2%), followed by visual field defects (38%). CONCLUSIONS BD was found in 9.4% of patients in our VENOST series. Patients with BD were younger and showed a male predominance. The functional outcome of CVST in patients with BD was good; only 12% of patients presenting with cranial nerve involvement and altered consciousness at the beginning had a poor outcome (modified Rankin Score ⩾2).

Crossing Y-Solitaire thrombectomy as a rescue treatment for refractory acute occlusions of the middle cerebral artery

Background Mechanical thrombectomy using a stent retriever has become the standard of care for acute large-vessel occlusions in the anterior circulation. Clots that are refractory to single stent retriever thrombectomy remain a challenge for neurointerventionalists. Objective To assess the efficacy and safety of double stent retriever (crossing Y-Solitaire) thrombectomy as a rescue treatment for acute middle cerebral artery (MCA) occlusions that are refractory to single stent retriever thrombectomy. Methods We retrospectively reviewed the databases of our hospitals to identify patients who presented with an acute MCA occlusion and were treated with crossing Y-Solitaire thrombectomy. The angiographic (Thrombolysis in Cerebral Infarction (TICI) scale) and clinical outcomes (National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores) and complications were assessed. Results Ten patients were included in the study. The median initial NIHSS score and Alberta Stroke Program Early CT Score (ASPECTS) were 19.0 and 9.6, respectively. Crossing Y-Solitaire thrombectomy was performed as a rescue technique after unsuccessful single Solitaire thrombectomy passes in all cases. Successful recanalization (TICI 2b/3) was achieved in 8 (80%) patients. We observed asymptomatic reperfusion hemorrhages in 2 (20%) patients. No procedural related complications were seen other than reversible vasospasms in 5 (50%) patients. Sixty percent of the patients had a mRS score of between 2 and 0 at 90 days after the procedure. There was no mortality. Conclusion Crossing Y-Solitaire thrombectomy seems to be an effective and safe alternative rescue technique to treat refractory MCA bifurcation occlusions that are refractory to standard thrombectomy procedures.

CLINICAL FEATURES OF CANCER ASSOCIATED ISCHEMIC STROKE

Introduction Cerebrovascular disease is the second most common cause of central nervous system involvement in cancer patients after metastases. Procoagulant substances secreted by tumour cells, cancer therapy, and embolus from tumour have been implicated in ischemic stroke (IS) in cancer patients. Methods Four thousand twenty patients with IS were prospectively recorded to the Istanbul Medical School Stroke Registry from August 1997 to May 2016. Ninety-two patients with IS and cancer and 3928 IS patients without cancer constituted the two groups. Results Hypertension, hyperlipidemia, and congestive heart failure were less commonly encountered in cancer stroke patients. Lacunar and posterior circulation syndromes were less common and total anterior circulation syndrome was more common in cancer patients (p<0.001). Multiple territory infarcts were more frequently seen in patients having overt or non-overt disseminated intravascular coagulopathy (DIC) compared to those without DIC. Median survival was significantly shorter in patients with cancer-related stroke. Conclusion Cancer associated stroke without other underlying etiology is a specific group of stroke patients presenting with multiple territorial infarcts, overt or non-overt disseminated intravascular coagulopathy, and poor prognosis.

Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design

Background Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. Key hypotheses/aims (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. Design Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case–control study enrolling patients aged 18–49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient–control pairs enrolled by the end of 2018. Summary SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.