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Background: The underlying risk factors for young-onset cryptogenic ischaemic stroke (CIS) remain unclear. This multicentre study aimed to explore the association between heavy alcohol consumption and CIS with subgroup analyses stratified by sex and age., Methods: Altogether, 540 patients aged 18-49 years (median age 41; 47.2% women) with a recent CIS and 540 sex-matched and age-matched stroke-free controls were included. Heavy alcohol consumption was defined as >7 (women) and >14 (men) units per week or at least an average of two times per month ≥5 (women) and ≥7 (men) units per instance (binge drinking). A conditional logistic regression adjusting for age, sex, education, hypertension, cardiovascular diseases, diabetes, hypercholesterolaemia, current smoking, obesity, diet and physical inactivity was used to assess the independent association between alcohol consumption and CIS., Results: Patients were twice as more often heavy alcohol users compared with controls (13.7% vs 6.7%, p<0.001), were more likely to have hypertension and they were more often current smokers, overweight and physically inactive. In the entire study population, heavy alcohol consumption was independently associated with CIS (adjusted OR 2.11; 95% CI 1.22 to 3.63). In sex-specific analysis, heavy alcohol consumption was associated with CIS in men (2.72; 95% CI 1.25 to 5.92), but not in women (1.56; 95% CI 0.71 to 3.41). When exploring the association with binge drinking alone, a significant association was shown in the entire cohort (2.43; 95% CI 1.31 to 4.53) and in men (3.36; 95% CI 1.44 to 7.84), but not in women., Conclusions: Heavy alcohol consumption, particularly binge drinking, appears to be an independent risk factor in young men with CIS., Competing Interests: Competing interests: JP: shareholder of Olvi Oyj. TT: has served/serves on scientific advisory boards for Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Inventiva and Portola Pharm., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Importance: One of 10 patients develop epilepsy in the late phase after cerebral venous thrombosis (CVT) diagnosis but predicting the individual risk is difficult., Objective: To develop and externally validate a prognostic score to estimate the individual risk of post-CVT epilepsy., Design, Setting, and Participants: This observational cohort study included both retrospective and prospective patients enrolled from 1994 through 2022. For development of the DIAS3 score, data from the International CVT Consortium (n = 1128), a large international hospital-based multicenter CVT cohort, were used. For validation, data from 2 independent multicenter cohorts, the ACTION-CVT (n = 543) and the Israel CVT study (n = 556), were used. Of 2937 eligible, consecutively enrolled adult patients with radiologically verified CVT, 710 patients with a history of epilepsy prior to CVT, follow-up less than 8 days, and missing late seizure status were excluded., Exposure: The prediction score (DIAS3) was developed based on available literature and clinical plausibility and consisted of 6 readily available clinical variables collected during the acute phase: decompressive hemicraniectomy, intracerebral hemorrhage at presentation, age, seizure(s) in the acute phase (excluding status epilepticus), status epilepticus in the acute phase, and subdural hematoma at presentation., Main Outcome and Measure: Time to a first late seizure, defined as occurring more than 7 days after diagnosis of CVT., Results: Of 1128 patients included in the derivation cohort (median age, 41 [IQR, 30-53] years; 805 women [71%]), 128 (11%) developed post-CVT epilepsy during a median follow-up of 12 (IQR, 3-26) months. According to the DIAS3 score, the predicted 1-year and 3-year risk of epilepsy in individual patients ranged from 7% to 68% and 10% to 83%, respectively. Internal and external validation showed adequate discrimination in the derivation cohort (1 year and 3 years: C statistic, 0.74; 95% CI, 0.70-0.79) and the 2 independent validation cohorts, (ACTION-CVT) 1 year: C statistic, 0.76; 95% CI, 0.67-0.84; 3 years: C statistic, 0.77; 95% CI, 0.66-0.84; and Israel CVT study 1 year: C statistic, 0.80; 95% CI, 0.75-0.86. Calibration plots indicated adequate agreement between predicted and observed risks., Conclusions and Relevance: The DIAS3 score (freely available online) is a simple tool that can help predict the risk of post-CVT epilepsy in individual patients. The model can improve opportunities for personalized medicine and may aid in decision-making regarding antiseizure medication, patient counseling, and facilitation of research on epileptogenesis in CVT.

Background: Incidence of cryptogenic ischemic stroke (CIS) in young adults is increasing. Early left atrial (LA) myopathy might be 1 of the underlying mechanisms, but this has only been scarcely explored., Objectives: The purpose of this study was to assess the association between increased LA stiffness and CIS in young adults., Methods: In the multicenter SECRETO (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome) study, LA function was analyzed by speckle tracking echocardiography in 150 CIS patients (aged 18-49 years) and 150 age- and sex-matched controls. Minimum and maximum LA volumes, LA reservoir and contractile strain were measured. LA stiffness was calculated by the ratio: mitral peak E-wave velocity divided by mitral annular e' velocity (E/e')/LA reservoir strain and considered increased if ≥0.22. Increased LA volumes, LA stiffness, and/or reduced LA strain indicated LA myopathy. Logistic regression was used to determine the relation between LA stiffness and CIS and the clinical variables associated with LA stiffness., Results: Increased LA stiffness was found in 36% of patients and in 18% of controls ( P  < 0.001). Increased LA stiffness was associated with a 2.4-fold (95% CI: 1.1-5.3) higher risk of CIS after adjustment for age, sex, comorbidities, and echocardiographic confounders ( P  = 0.03). In patients, obesity, pre-CIS antihypertensive treatment, older age, and lower LA contractile strain were all related to increased LA stiffness (all P  < 0.05)., Conclusions: LA myopathy with increased LA stiffness and impaired LA mechanics more than doubles the risk of CIS in patients under the age of 50 years. This provides new insights into the link between LA dysfunction and CIS at young ages. (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome [SECRETO]; NCT01934725)., Competing Interests: The SECRETO study has been funded by the 10.13039/501100002341Academy of Finland under grant numbers 318075 and 322656, Helsinki and Uusimaa Hospital District (TYH2018318), and 10.13039/501100006306Sigrid Juselius Foundation. Dr Cramariuc has received clinical researcher funds and open project support from the Regional Health Authorities in Western Norway (project numbers F-12557 and F-12615). Dr Sarkanen has received grant number 322663 from the Academy of Finland. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.PERSPECTIVESCOMPETENCY IN MEDICAL KNOWLEDGE: Young adults with increased LA stiffness have significantly higher risk of CIS independent of LA size and in the absence of atrial fibrillation. TRANSLATIONAL OUTLOOK: Patients with premature LA disease may benefit from early intervention, like antithrombotic therapy. This should be further investigated in clinical studies addressing preventive and therapeutic interventions in young patients at high risk of ischemic stroke., (© 2024 The Authors.)

Background and Purpose: A prognostic score was developed to predict dependency and death after cerebral venous thrombosis (CVT) to identify patients for targeted therapy in future clinical trials., Methods: Data from the International CVT Consortium were used. Patients with pre-existent functional dependency were excluded. Logistic regression was used to predict poor outcome (modified Rankin Scale score 3-6) at 6 months and Cox regression to predict 30-day and 1-year all-cause mortality. Potential predictors derived from previous studies were selected with backward stepwise selection. Coefficients were shrunk using ridge regression to adjust for optimism in internal validation., Results: Of 1454 patients with CVT, the cumulative number of deaths was 44 (3%) and 70 (5%) for 30 days and 1 year, respectively. Of 1126 patients evaluated regarding functional outcome, 137 (12%) were dependent or dead at 6 months. From the retained predictors for both models, the SI 2 NCAL 2 C score was derived utilizing the following components: absence of female-sex-specific risk factor, intracerebral hemorrhage, infection of the central nervous system, neurological focal deficits, coma, age, lower level of hemoglobin (g/l), higher level of glucose (mmol/l) at admission, and cancer. C-statistics were 0.80 (95% confidence interval [CI] 0.75-0.84), 0.84 (95% CI 0.80-0.88) and 0.84 (95% CI 0.80-0.88) for the poor outcome, 30-day and 1-year mortality model, respectively. Calibration plots indicated a good model fit between predicted and observed values. The SI 2 NCAL 2 C score calculator is freely available at www.cerebralvenousthrombosis.com., Conclusions: The SI 2 NCAL 2 C score shows adequate performance for estimating individual risk of mortality and dependency after CVT but external validation of the score is warranted., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objectives: We examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association., Materials and Methods: This prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura., Results: After adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS., Conclusions: Abdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Objectives: There is a worldwide increase in the incidence of stroke in young adults, with major regional and ethnic differences. Advancing knowledge of ethnic and regional variation in causes and outcomes will be beneficial in implementation of regional health care services. We studied the global distribution of risk factors, causes, and 3-month mortality of young patients with ischemic stroke, by performing a patient data meta-analysis from different cohorts worldwide., Methods: We performed a pooled analysis of individual patient data from cohort studies that included consecutive patients with ischemic stroke aged 18-50 years. We studied differences in prevalence of risk factors and causes of ischemic stroke between different ethnic and racial groups, geographic regions, and countries with different income levels. We investigated differences in 3-month mortality by mixed-effects multivariable logistic regression., Results: We included 17,663 patients from 32 cohorts in 29 countries. Hypertension and diabetes were most prevalent in Black (hypertension, 52.1%; diabetes, 20.7%) and Asian patients (hypertension 46.1%, diabetes, 20.9%). Large vessel atherosclerosis and small vessel disease were more often the cause of stroke in high-income countries (HICs; both p < 0.001), whereas "other determined stroke" and "undetermined stroke" were higher in low and middle-income countries (LMICs; both p < 0.001). Patients in LMICs were younger, had less vascular risk factors, and despite this, more often died within 3 months than those from HICs (odds ratio 2.49; 95% confidence interval 1.42-4.36)., Discussion: Ethnoracial and regional differences in risk factors and causes of stroke at young age provide an understanding of ethnic and racial and regional differences in incidence of ischemic stroke. Our results also highlight the dissimilarities in outcome after stroke in young adults that exist between LMICs and HICs, which should serve as call to action to improve health care facilities in LMICs., (© 2021 American Academy of Neurology.)

What Is Known and Objective: Oxcarbazepine (OXC) is an antiepileptic drug. Patients suffering from chronic kidney disease with an estimated glomerular filtration rate below 30 ml/min/1.73 m 2 require dose adjustments for OXC., Case Summary: A 31-year-old man was admitted with a history of diplopia, ataxia and dizziness attacks that had disappeared after a regular haemodialysis sessions for three months. Medical history was remarkable for primary antiphospholipid syndrome (APS). However, no signs of new-onset APS-related neurological involvement were present. Then, it was revealed that the patient had been using 2400 mg/day of OXC for four months, despite the prescription of half of this dose. Serum OXC level was 50 mcg/ml (reference: 3-35 mcg/ml) before a regular haemodialysis session. All symptoms disappeared in a few days after reducing to 1200 mg/day and never recurred., What Is New and Conclusion: We reported a chronic OXC intoxication in a patient on maintenance haemodialysis. To the best of our knowledge, it is the first chronic OXC intoxication case in the literature. It could be related to episodic removal of OXC and its metabolites via haemodialysis. Consequently, dose modification of drugs is a pivotal point in haemodialysis patients. Chronic drug intoxications must be kept in mind in haemodialysis patients with unexplained symptoms., (© 2021 John Wiley & Sons Ltd.)

Background and Aims: Cryptogenic ischemic strokes (CIS) are treated with antiplatelets for stroke prevention in routine clinical practice. The objective of this study was to investigate whether the CHADS 2 and CHA 2 DS 2 -VASc scores may be used to identify the patients with CIS at higher risk of ischemic stroke despite antiplatelet therapy., Material and Methods: We calculated CHADS 2 and CHA 2 DS 2 -VASc scores in patients with first ever CIS; those previously managed with antiplatelets (AP group) and in those without antiplatelets (non-AP group), using the prospectively recorded data of the Istanbul Medical School Stroke Registry from 1996-2014., Results: Of the 4466 IS patients, 886 patients with first ever IS had complete data for score calculation. Seventy-five (39 women) of them were diagnosed with CIS. CHADS 2 and CHA 2 DS 2 -VASc scores were significantly higher in the AP group of 19 patients in comparison to the non-AP group of 56 patients (P = 0.005 and P = 0.009, respectively). ROC curve analyses showed an area under curve (AUC) of 0.705 (CI: 0.57-0.84; P = 0.008) for CHADS 2 score ≥3 and AUC of 0.699 (CI: 0.57-0.82; P = 0.01) for CHA 2 DS 2 -VASc score ≥4. Vascular diseases were more frequent in the AP group and these patients were older than the patients in the non-AP group (P = 0.025, P = 0.024; respectively)., Conclusions: CHA 2 DS 2 -VASc score ≥ 4 and CHADS 2 score ≥3 may be used as a predictor of the occurrence of IS despite regular antiplatelet use and suggest an embolic source which will respond better to anticogulation. Our results support that CHADS 2 and CHA 2 DS 2 -VASc scores may be useful to identify subgroups among patients with CIS for individualizing diagnostic approach, planning future workup and preventive treatment., Competing Interests: None

Objective: To assess the association between migraine and cryptogenic ischemic stroke (CIS) in young adults, with subgroup analyses stratified by sex and presence of patent foramen ovale (PFO)., Methods: We prospectively enrolled 347 consecutive patients aged 18 to 49 years with a recent CIS and 347 age- and sex-matched (±5 years) stroke-free controls. Any migraine and migraine with (MA) and migraine without aura (MO) were identified by a screener, which we validated against a headache neurologist. We used conditional logistic regression adjusting for age, education, hypertension, diabetes, waist-to-hip ratio, physical inactivity, current smoking, heavy drinking, and oral estrogen use to assess independent association between migraine and CIS. The effect of PFO on the association between migraine and CIS was analyzed with logistic regression in a subgroup investigated with transcranial Doppler bubble screen., Results: The screener performance was excellent (Cohen kappa > 0.75) in patients and controls. Compared with nonmigraineurs, any migraine (odds ratio [OR] = 2.48, 95% confidence interval [CI] = 1.63-3.76) and MA (OR = 3.50, 95% CI = 2.19-5.61) were associated with CIS, whereas MO was not. The association emerged in both women (OR = 2.97 for any migraine, 95% CI = 1.61-5.47; OR = 4.32 for MA, 95% CI = 2.16-8.65) and men (OR = 2.47 for any migraine, 95% CI = 1.32-4.61; OR = 3.61 for MA, 95% CI = 1.75-7.45). Specifically for MA, the association with CIS remained significant irrespective of PFO. MA prevalence increased with increasing magnitude of the right-to-left shunt in patients with PFO., Interpretation: MA has a strong association with CIS in young patients, independent of vascular risk factors and presence of PFO. ANN NEUROL 2021;89:242-253., (© 2020 American Neurological Association.)

Background: Periodic EEG patterns are mostly associated with critical illnesses and acute disruptions of the central nervous system. Periodic or cyclic seizures are extremely rare phenomena, most of which are nonconvulsive, only reported in critically ill patients. Here we report a patient with periodic focal impaired awareness seizures following a minor stroke and address possible pathophysiological mechanisms., Case: A 49 years old male patient presented with periodic seizures, associated with an acute stroke in the left occipital and parietal regions. These focal seizures, recorded during long-term video-EEG monitoring in the scalp EEG, appeared every 9-11 min, and responded to iv valproic acid treatment but not to iv treatments of diazepam, phenytoin, and levetiracetam., Discussion: We believe that the blood-brain barrier disruption due to stroke, in conjunction with hyperglycemia and antiphospholipid antibodies have led to an imbalance of the surrounding tissue and sustained hyperexcitability to a point of pacemaker potentials. It is tempting to speculate that repetitive cycles of cortical spreading depression due to tissue injury have aided the periodicity of the seizures., Conclusion: Continuous EEG monitoring is crucial, not only to diagnose and appropriately treat accompanying subtle seizures but also to further understand the underlying intriguing pathophysiological processes like periodicity., (© 2021 The Authors.)

Objective: To examine the incidence, characteristics, treatment, and predictors of late seizures (LS) after cerebral venous thrombosis (CVT), we described these features in a registry of 1,127 patients with CVT., Methods: We included consecutive adult patients from an international consortium of 12 hospital-based CVT registries. We excluded patients with a history of epilepsy or with <8 days of follow-up. We defined LS as seizures occurring >7 days after diagnosis of CVT. We used multivariable Cox regression to identify predictors of LS., Results: We included 1,127 patients with CVT. During a median follow-up of 2.0 years (interquartile range [IQR] 1.0-6.3), 123 patients (11%) experienced ≥1 LS (incidence rate for first LS 30 per 1,000 person-years, 95% confidence interval [CI] 25-35). Median time to first LS was 5 months (IQR 1-16 months). Baseline predictors of LS included status epilepticus in the acute phase (hazard ratio [HR] 7.0, 95% CI 3.9-12.6), decompressive hemicraniectomy (HR 4.2, 95% CI 2.4-7.3), acute seizure(s) without status epilepticus (HR 4.1, 95% CI 2.5-6.5), subdural hematoma (HR 2.3, 95% CI 1.1-4.9), and intracerebral hemorrhage (HR 1.9, 95% CI 1.1-3.1). Eighty-five patients (70% of patients with LS) experienced a recurrent seizure during follow-up, despite the fact that 94% received antiepileptic drug treatment after the first LS., Conclusion: During a median follow-up of 2 years, ≈1 in 10 patients with CVT had LS. Patients with baseline intracranial bleeding, patients with acute symptomatic seizures, and those who underwent decompressive hemicraniectomy were at increased risk of developing LS. The high recurrence risk of LS justifies epilepsy diagnosis after a first LS., (© 2020 American Academy of Neurology.)

Objective: To identify characteristics, predictors, and outcomes of acute symptomatic seizures (ASS) in cerebral venous thrombosis (CVT), we investigated 1,281 consecutive adult patients with CVT included from 12 hospitals within the International CVT Consortium., Methods: We defined ASS as any seizure between symptom onset and 7 days after diagnosis of CVT. We stratified ASS into prediagnosis and solely postdiagnosis ASS. Status epilepticus (SE) was also analyzed separately. We analyzed predictors for ASS and the association between ASS and clinical outcome (modified Rankin Scale) with multivariable logistic regression., Results: Of 1,281 eligible patients, 441 (34%) had ASS. Baseline predictors for ASS were intracerebral hemorrhage (ICH; adjusted odds ratio [aOR] 4.1, 95% confidence interval [CI] 3.0-5.5), cerebral edema/infarction without ICH (aOR 2.8, 95% CI 2.0-4.0), cortical vein thrombosis (aOR 2.1, 95% CI 1.5-2.9), superior sagittal sinus thrombosis (aOR 2.0, 95% CI 1.5-2.6), focal neurologic deficit (aOR 1.9, 95% CI 1.4-2.6), sulcal subarachnoid hemorrhage (aOR 1.6, 95% CI 1.1-2.5), and female-specific risk factors (aOR 1.5, 95% CI 1.1-2.1). Ninety-three (7%) patients had solely postdiagnosis ASS, best predicted by cortical vein thrombosis (positive/negative predictive value 22%/92%). Eighty (6%) patients had SE, independently predicted by ICH, focal neurologic deficits, and cerebral edema/infarction. Neither ASS nor SE was independently associated with outcome., Conclusion: ASS occurred in one-third of patients with CVT and was associated with brain parenchymal lesions and thrombosis of the superficial system. In the absence of prediagnosis ASS, no subgroup was identified with sufficient risk of postdiagnosis ASS to justify prophylactic antiepileptic drug treatment. We found no association between ASS and outcome., (© 2020 American Academy of Neurology.)

Background: Early diagnosis of cerebral venous sinus thrombosis (CVST) associated with reproductive health-related risk factors (RHRF) including pregnancy, puerperium, and oral contraceptive (OC) use can prevent severe neurological sequelae; thus, the symptoms must be documented in detail for each group., Methods: Out of 1144 patients with CVST, a total of 777 women were enrolled from a multicenter for the study of cerebral venous sinus thrombosis (VENOST). Demographic, biochemical, clinical, and radiological aspects were compared for 324 cases with RHRF and 453 cases without RHRF., Results: The mean age of the RHRF (-) group (43.2 ± 13 years) was significantly higher than of the RHRF (+) group (34 ± 9 years). A previous history of deep venous thrombosis (3%), isolated cavernous sinus involvement (1%), cranial neuropathy (13%), comorbid malignancy (7%), and its disability scores after 12 months (9%) were significantly higher in the RHRF (-) group. The RHRF (+) group consisted of 44% cases of puerperium, 33% cases of OC users and 23% of pregnant women. The mean age was found to be higher in OC users (38 ± 9 years). A previous history of deep venous thrombosis was slightly higher in the pregnancy subgroup (4%). Epileptic seizures were more common in the puerperium group (44%)., Conclusion: The results of our study indicate that the risk of CSVT increases parallel to age, OC use, and puerperium period. In addition, when considering the frequency of findings and symptoms, epileptic seizures in the puerperium subgroup of the RHRF (+) group and malignancies in the RHRF (-) group may accompany the CSVT. In daily practice, predicting these risks for the CSVT and early recognition of the symptoms will provide significant benefits to patients., Competing Interests: The authors declared that they have no conflicts of interest for this article., (Copyright © 2020 Derya Uluduz et al.)

Purpose: To improve prescribing in older adults, criterion sets have been introduced from different countries. While current criterion sets are useful to some extent, they do not meet the need in some European countries. Turkish inappropriate medication use in the elderly (TIME) criteria was planned to meet this need., Methods: In phase 1, the user friendly sets: STOPP/START version2 and CRIME criteria were combined. National experts composed of geriatricians and non-geriatricians were invited to review and comment. In phase 2, thorough literature review was performed and reference-based revisions, omissions, and additions were made. Explanatory additions were added to some criteria to improve application in practice. In phase 3, all working group members reviewed the criteria/explanations and agreed on the final content., Results: Phase 1 was performed by 49 expert academicians between May and October 2016. Phase 2 was performed by 23 working group academicians between October 2016 and November 2018 and included face-to-face interviews between at least two geriatrician members and one criterion-related specialist. Phase 3 was completed between November 2018-March 2019 with review and approval of all criteria by working group academicians. As a result, 55 criteria were added, 17 criteria were removed, and 60 criteria were modified from the first draft. A total of 153 TIME criteria composed of 112 TIME-to-STOP and 41 TIME-to-START criteria were introduced., Conclusion: TIME criteria is an update screening tool that differs from the current useful tools by the interactive study of experts from geriatrics and non-geriatrics, inclusion of practical explanations for some criteria and by its eastern European origin. TIME study respectfully acknowledges its roots from STOPP/START and CRIME criteria. Studies are needed whether it would lead improvements in older adults' health.

Purpose: The aim of this study is to evaluate the presence and prognostic impact of early seizures in cerebral venous sinus thrombosis patients (CVST)., Method: VENOST is a retrospective and prospective national multicenter observational study. CVST patients with or without epileptic seizures (ES) were analyzed and compared in terms of demographic and imaging data, causative factors, clinical variables, and prognosis in a total of 1126 patients., Results: The mean age of the patients in the ES group was 39.73 ± 12.64 and 40.17 ± 14.02 years in the non-ES group (p > 0.05). Epileptic seizures were more common (76.6 %) in females (p < 0.001). Early ES occurred in 269 of 1126 patients (23.9 %). Epileptic seizures mainly presented in the acute phase (71.4 %) of the disease (p < 0.001). Majority of these (60.5 %) were in the first 24 h of the CVST. The most common neurological signs were focal neurologic deficits (29.9 %) and altered consciousness (31.4 %) in the ES group. Superior sagittal sinus (SSS) and cortical veins (CV) involvement were the most common sites of thrombosis and the mostly related etiology were found puerperium in seizure group (30.3 % vs 13.9 %). Patients with seizures had worse outcome in the first month of the disease (p < 0.001) but these did not have any influence thereafter., Conclusions: In this largest CVST cohort (VENOST) reported female sex, presence of focal neurological deficits and altered consciousness, thrombosis of the SSS and CVs, hemorrhagic infarction were risk factors for ES occurrence in patients with CVST., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to disclose., (Copyright © 2020. Published by Elsevier Ltd.)

A 24-year-old female patient diagnosed with cyanotic CHD had undergone a correction procedure at the age of eight. She had a normal motor and mental development until the age of 23. Later she had functional and cognitive decline following heart failure. Brain MRI showed enlargement of the cerebral arterial and venous system. The changes of central nervous system vasculature occurring in operated cyanotic CHD are not well known. Thanks to advances in this field, more cyanotic CHD patients reach adulthood nowadays and clinicians need to be familiar with the neurological conditions and potential neuroradiological changes.

Introduction: Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients., Methods and Analysis: The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence., Ethics and Dissemination: Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This study was performed to determine the rate of cerebral venous sinus thrombosis (CVST) among cases of Behçet's 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)., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Ischaemic stroke in young adults encompasses approximately 5 - 15% of all ischaemic strokes, depending on the selected upper age limit. The key features of the disease, including incidence, risk factors, underlying causes, mortality, outcomes, as well as long-term risks of recurrent events are different from those for elderly patients. There is also evidence indicating that these characteristics may differ ethnically and geographically. It is clinically important to recognize such differences not only for correct diagnosis and treatment, but also for introducing accurate preventive measures. Ethnic differences may stem from several factors, including genetic influence, and necessitate different approaches, such as personalized diagnostic work-up based on patient characteristics., Conclusion: In this review, we summarize and discuss the existing data on the geographic and ethnic differential characteristics of young adult ischaemic stroke., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objectives: Oligoclonal bands (OCB) of immunoglobulins (IgG) in the cerebrospinal fluid (CSF) provides an evidence for the humoral response and have been screened in the CSF and serum of patients revealing 5 different patterns. In this study, patients with Behçet's disease (BD) are screened in a larger sample to potentially provide information about the possible role of CSF oligoclonal immunoglobulins in the diagnosis of this disease., Methods: Paired CSF and serum samples from 121 consecutive BD patients with neurological complaints (43 women and 78 men) were included in this study. Parenchymal NBD was diagnosed in 74 patients, and 22 patients had cerebral venous sinus thrombosis (CVST); of the remaining patients, 18 had primary headache disorders not directly associated with BD, and 7 had a cerebrovascular event. OCB of IgG were detected by isoelectric focusing on agarose and immunoblotting of matched serum and CSF sample pairs. Intrathecal production of IgG only is considered positive (Pattern 2 or 3)., Results: In the whole group, only 8 patients had OCB in the CSF showing pattern 2. All these positive cases had parenchymal neuro-BD (10.8% positive and 78.4% negative in parenchymal neuro-BD group). All other groups were negative., Conclusions: The rare presence of oligoclonal IgG bands in CSF can be utilized as another laboratory finding in the diagnosis of NBD.

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.

Introduction: Treatment of spontaneous supratentorial intracerebral hemorrhage (SICH) is controversial. This study aims to evaluate the outcome and invasiveness of one surgical approach that provides complete evacuation of SICH, the image-guided keyhole evacuation., Methods: The technique was employed in 20 consecutive patients, nine of whom harbored deep hematomas. The hematoma was evacuated through a keyhole minicraniotomy, 2.5 cm in diameter. Computerised tomographic (CT) scan was performed at the end of the procedure to confirm completeness of evacuation. Invasiveness was assessed by comparing initial neurological status determined by Glasgow Coma Scale (GCS) scores and National Institutes of Health Stroke Scale (NIHSS) scores with the third and seventh postoperative day scores, and by radiological findings. Outcome at six months was assessed by the Extended Glasgow Outcome Scale, and by comparing the initial and 6 month modified Rankin Scale scores., Results: Mean age was 63.7+/-14.8 years, mean volume was 41.6+/-17.5 mL, and mean time to surgery was 17.6+/-13.2 h. CT scans at the end of the procedure showed complete evacuation (mean 97.5%), and 60% decrease of both mean midline shift and mean edema volume (p=0.005). Neurological assessment at the end of the first postoperative week showed significant improvement (p<0.0001). At six months, 90% of the patients had achieved recovery to independence, and one patient had died., Conclusion: The image-guided keyhole approach allowed prompt evacuation of SICH and resulted in a high rate of functional recovery and low mortality. This is a minimally invasive technique that is highly effective in immediate and complete hematoma evacuation.

Objective: The aim of this study was to determine the long term clinical course and prognosis of subclinical ('silent') neurological involvement in Behçet's disease (BD)., Methods: We included patients with BD who did not have any neurological complaints other than headache, dizziness or other non-specific complaints, that showed abnormal neurological findings (Silent Group). We compared these patients with the patients with overt parenchymal neuro-Behçet's disease (Overt Group). Cases with at least 8 years of follow-up were included., Results: There were 22 patients in the Silent Group (15M, 7F), with a mean follow-up of 12.8 +/- 4 years. Magnetic resonance imaging was abnormal in 8 of 21 patients, while neuropsychological testing revealed mild abnormalities in 15 of 20 patients. During the follow up period, 3 patients of the Silent Group had 4 overt neurological attacks. In the last visit, 21 patients were independent, while one that had previously developed overt neurological attack was deceased. The Overt Group consisted of 51 patients (45M, 6F). In the Overt Group the ratio of males was higher, nearing a marginal significance (p = 0.051); whereas age at onset of BD, and frequency of other organ manifestations of BD were not different. In the Overt Group at the final visit, 19 patients were independent (37%), while the remaining were either dependent to others, or deceased, which was significantly higher when compared to the Silent Group(p=0.005)., Conclusion: Silent neurological involvement in BD seems to represent a milder form of the disease, since the mortality and disability rate in this group is significantly low.