Outcomes of Decompressive Surgery for Patients With Severe Cerebral Venous Thrombosis: DECOMPRESS2 Observational Study.

BACKGROUND: Decompressive neurosurgery is recommended for patients with cerebral venous thrombosis (CVT) who have large parenchymal lesions and impending brain herniation. This recommendation is based on limited evidence. We report long-term outcomes of patients with CVT treated by decompressive neurosurgery in an international cohort. METHODS: DECOMPRESS2 (Decompressive Surgery for Patients With Cerebral Venous Thrombosis, Part 2) was a prospective, international cohort study. Consecutive patients with CVT treated by decompressive neurosurgery were evaluated at admission, discharge, 6 months, and 12 months. The primary outcome was death or severe disability (modified Rankin Scale scores, 5-6) at 12 months. The secondary outcomes included patient and caregiver opinions on the benefits of surgery. The association between baseline variables before surgery and the primary outcome was assessed by multivariable logistic regression. RESULTS: A total of 118 patients (80 women; median age, 38 years) were included from 15 centers in 10 countries from December 2011 to December 2019. Surgery (115 craniectomies and 37 hematoma evacuations) was performed within a median of 1 day after diagnosis. At last assessment before surgery, 68 (57.6%) patients were comatose, fixed dilated pupils were found unilaterally in 27 (22.9%) and bilaterally in 9 (7.6%). Twelve-month follow-up data were available for 113 (95.8%) patients. Forty-six (39%) patients were dead or severely disabled (modified Rankin Scale scores, 5-6), of whom 40 (33.9%) patients had died. Forty-two (35.6%) patients were independent (modified Rankin Scale scores, 0-2). Coma (odds ratio, 2.39 [95% CI, 1.03-5.56]) and fixed dilated pupil (odds ratio, 2.22 [95% CI, 0.90-4.92]) were predictors of death or severe disability. Of the survivors, 56 (78.9%) patients and 61 (87.1%) caregivers expressed a positive opinion on surgery. CONCLUSIONS: Two-thirds of patients with severe CVT were alive and more than one-third were independent 1 year after decompressive surgery. Among survivors, surgery was judged as worthwhile by 4 out of 5 patients and caregivers. These results support the recommendation to perform decompressive neurosurgery in patients with CVT with impending brain herniation.

Coma in adult cerebral venous thrombosis: The BEAST study.

BACKGROUND AND PURPOSE: Coma is an independent predictor of poor clinical outcomes in cerebral venous thrombosis (CVT). We aimed to describe the association of age, sex, and radiological characteristics of adult coma patients with CVT. METHODS: We used data from the international, multicentre prospective observational BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) study. Only positively associated variables with coma with <10% missing data in univariate analysis were considered for the multivariate logistic regression model. RESULTS: Of the 596 adult patients with CVT (75.7% women), 53 (8.9%) patients suffered coma. Despite being a female-predominant disease, the prevalence of coma was higher among men than women (13.1% vs. 7.5%, p = 0.04). Transverse sinus thrombosis was least likely to be associated with coma (23.9% vs. 73.3%, p < 0.001). The prevalence of superior sagittal sinus thrombosis was higher among men than women in the coma sample (73.6% vs. 37.5%, p = 0.01). Men were significantly older than women, with a median (interquartile range) age of 51 (38.5-60) versus 40 (33-47) years in the coma (p = 0.04) and 44.5 (34-58) versus 37 (29-48) years in the non-coma sample (p < 0.001), respectively. Furthermore, an age- and superior sagittal sinus-adjusted multivariate logistic regression model found male sex (odds ratio = 1.8, 95% confidence interval [CI] = 1.0-3.4, p = 0.04) to be an independent predictor of coma in CVT, with an area under the receiver operating characteristic curve of 0.61 (95% CI = 0.52-0.68, p = 0.01). CONCLUSIONS: Although CVT is a female-predominant disease, men were older and nearly twice as likely to suffer from coma than women.

A scoring tool to predict mortality and dependency after cerebral venous thrombosis.

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 SI2 NCAL2 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 SI2 NCAL2 C score calculator is freely available at www.cerebralvenousthrombosis.com. CONCLUSIONS: The SI2 NCAL2 C score shows adequate performance for estimating individual risk of mortality and dependency after CVT but external validation of the score is warranted.

Cerebral venous thrombosis following an immunoglobulin-E mediated anaphylactic reaction.

BACKGROUND: Prothrombotic and pro-inflammatory states are known cerebral venous thrombosis risk factors. To date, two cases of venous thrombotic events after immunoglobulin-E mediated anaphylaxis have been reported. Herein, we describe the first case of cerebral venous thrombosis in close temporal relation with an immunoglobulin-E mediated anaphylactic event. CASE DESCRIPTION: A 51-year-old female presented with headache, language, and mental disturbance lasting for two days. Two days before the onset, she had undergone a provocative test with deflazacort to study an allergy history; after the test she developed a severe anaphylactic reaction. There were no other comorbidities, and in addition to contraceptive pill, she did not take other medications. On admission the patient was drowsy, with anomic aphasia, inattention and memory impairment. Magnetic Resonance Imaging depicted a left caudate and lenticulo-capsulo-thalamic venous infarct and thrombosis in the deep venous system. The patient was treated with anticoagulation and showed progressive improvement. Neoplastic and pro-thrombotic diseases were excluded. CONCLUSION: The close temporal association between the anaphylactic reaction and cerebral venous thrombosis suggests that anaphylactic reaction could have been a cerebral venous thrombosis precipitating factor. Immunoglobulin-E have been suggested to have prothrombotic activity by stimulating the release of platelet activation factor, thromboxane A2 and serotonin. This case adds on to the available information on possible cerebral venous thrombosis associated conditions.

Genome-Wide Association Study Identifies First Locus Associated with Susceptibility to Cerebral Venous Thrombosis.

OBJECTIVE: Cerebral venous thrombosis (CVT) is an uncommon form of stroke affecting mostly young individuals. Although genetic factors are thought to play a role in this cerebrovascular condition, its genetic etiology is not well understood. METHODS: A genome-wide association study was performed to identify genetic variants influencing susceptibility to CVT. A 2-stage genome-wide study was undertaken in 882 Europeans diagnosed with CVT and 1,205 ethnicity-matched control subjects divided into discovery and independent replication datasets. RESULTS: In the overall case-control cohort, we identified highly significant associations with 37 single nucleotide polymorphisms (SNPs) within the 9q34.2 region. The strongest association was with rs8176645 (combined p = 9.15 × 10-24 ; odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.76-2.31). The discovery set findings were validated across an independent European cohort. Genetic risk score for this 9q34.2 region increases CVT risk by a pooled estimate OR = 2.65 (95% CI = 2.21-3.20, p = 2.00 × 10-16 ). SNPs within this region were in strong linkage disequilibrium (LD) with coding regions of the ABO gene. The ABO blood group was determined using allele combination of SNPs rs8176746 and rs8176645. Blood groups A, B, or AB, were at 2.85 times (95% CI = 2.32-3.52, p = 2.00 × 10-16 ) increased risk of CVT compared with individuals with blood group O. INTERPRETATION: We present the first chromosomal region to robustly associate with a genetic susceptibility to CVT. This region more than doubles the likelihood of CVT, a risk greater than any previously identified thrombophilia genetic risk marker. That the identified variant is in strong LD with the coding region of the ABO gene with differences in blood group prevalence provides important new insights into the pathophysiology of CVT. ANN NEUROL 2021;90:777-788.

Mean Platelet Volume is a Prognostic Marker in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis.

BACKGROUND AND OBJECTIVES: There is conflicting data regarding the association between platelet parameters and prognosis of stroke patients treated with intravenous thrombolysis. We aimed to analyze this association in a cohort of patients treated with rtPA. MATERIAL AND METHODS: Retrospective, observational study in adult ischemic stroke patients treated with rtPA between January 2015 and February 2017. Demographic and clinical characteristics, stroke severity (NIHSS), etiology (TOAST), mean platelet volume (MPV), platelet count (PC), platelet distribution width (PDW) and functional outcome (mRS) at discharge and 90 days were recorded. The association between platelet parameters and unfavorable prognosis (mRS 3-6) was tested using non-parametric tests and logistic regression analysis. RESULTS: 267 patients were included, 134 (50.2%) females, with a median (IQR) age of 74 years (64-82). The median admission NIHSS was 14 (8-19) and the most frequent etiology was cardioembolism (n = 115, 43.1%). At discharge, 170 (63.7%) patients had mRS 3-6. MPV values were higher in patients with mRS 3-6 (median 8.2fL versus 7.8fL, p = 0.013). This association remained significant (OR = 1.36, 95% CI 1.003-1.832, p = 0.048) after adjustment for variables associated with prognosis. There were no significant associations between other platelet parameters and prognosis. There was a trend to unfavorable prognosis at 90 days in patients with higher MPV. Regarding the association between platelet parameters and hemorrhagic transformation, higher PDW was associated with more severe hemorrhagic transformation (PH1/PH2). CONCLUSIONS: Higher MPV values were associated with unfavorable prognosis at discharge in patients treated with intravenous thrombolysis. Future studies should address its added value in stroke prediction models.

Early Recanalization in Patients With Cerebral Venous Thrombosis Treated With Anticoagulation.

Background and Purpose- The hypothesis that venous recanalization prevents progression of venous infarction is not established in patients with cerebral venous thrombosis (CVT). Evidence is also scarce on the association between residual symptoms, particularly headache, and the recanalization grade. We aimed to assess, in patients with CVT treated with standard anticoagulation, (1) the rate of early venous recanalization, (2) whether lack of early recanalization was predictor of parenchymal brain lesion progression, and (3) the prevalence and features of persistent headache according to the recanalization grade achieved. Methods- PRIORITy-CVT (Pathophysiology of Venous Infarction - Prediction of Infarction and Recanalization in CVT) was a multicenter, prospective, cohort study including patients with newly diagnosed CVT. Standardized magnetic resonance imaging was performed at inclusion (≤24 hours of therapeutic anticoagulation), days 8 and 90. Potential imaging predictors of recanalization were predefined and analyzed at each anatomical segment. Primary outcomes were rate of early recanalization and brain lesion progression at day 8. Secondary outcomes were headache (days 8 and 90) and functional outcome (modified Rankin Scale at days 8 and 90). Results- Sixty eight patients with CVT were included, of whom 30 (44%) had parenchymal lesions. At the early follow-up (n=63; 8±2 days), 68% (n=43) of patients had partial recanalization and 6% (n=4) full recanalization. Early recanalization was associated both with early regression (P=0.03) and lower risk of enlargement of nonhemorrhagic lesions (P=0.02). Lesions showing diffusion restriction (n=12) were fully reversible in 66% of cases, particularly in patients showing early venous recanalization. Evidence of new or enlarged hemorrhagic lesions, headache at days 8 and 90, and unfavorable functional outcome at days 8 and 90 were not significantly different in patients achieving recanalization. Conclusions- Venous recanalization started within the first 8 days of therapeutic anticoagulation in most patients with CVT and was associated with early regression of nonhemorrhagic lesions, including venous infarction. There was an association between persistent venous occlusion at day 8 and enlargement of nonhemorrhagic lesions.

Herpes simplex virus 2 vasculitis as cause of ischemic stroke in a young immunocompromised patient.

Herpes simplex virus 2 (HSV-2) is a very rare cause of central nervous system (CNS) infections. We report a case of a young woman with a left middle cerebral artery (MCA) ischemic stroke. The patient had history of HIV-1 infection, with periods of therapeutic non-compliance. Initial computed tomography (CT) imaging studies showed stenosis of the M1 segment of the left MCA, and magnetic resonance imaging (MRI) confirmed infarction of the MCA territory. Serial transcranial Doppler ultrasound revealed progressive occlusion of the MCA and stenosis of the left anterior cerebral artery. Systemic investigation for other causes of stroke was normal. Lumbar puncture revealed a mildly inflammatory cerebrospinal fluid, and HSV-2 DNA was identified by PCR, with a positive viral load in favor of active replication. No other viral or microbiological infections were identified. MRI angiography confirmed a vasculitic process involving the left carotid artery, and a HSV-2 vasculitis diagnosis was assumed. The patient started acyclovir with improvement of clinical features and imaging abnormalities. In the HIV-infected patient, stroke is a multifactorial common cause of morbidity. The physician should take into account a broad differential diagnosis including rare causes and atypical presentations of common etiologies, including HSV-1 and HSV-2 CNS infection.

TNF-R1 Correlates with Cerebral Perfusion and Acute Ischemia Following Subarachnoid Hemorrhage.

BACKGROUND: Early cerebral hypoperfusion and ischemia occur after subarachnoid hemorrhage (SAH) and influence clinical prognosis. Pathophysiological mechanisms possibly involve inflammatory mediators. TNF-α has been associated with complications and prognosis after SAH. We investigated the relation of perfusion parameters and ischemic lesions, with levels of TNF-α main receptor, TNF-R1, after SAH, and their association with prognosis. METHODS: We included consecutive SAH patients admitted within the first 72 h of SAH onset. Blood samples were simultaneously collected from a peripheral vein and from the parent artery of the aneurysm. Levels of TNF-R1 were measured using ELISA (R&D Systems Inc., USA). CT perfusion and MRI studies were performed in the first 72 h. Correlation and logistic regression analysis were used to identify outcome predictors. RESULTS: We analyzed 41 patients. Increased levels of TNF-R1 correlated with increased Tmax (arterial: r = -0.37, p = 0.01) and prolonged MTT (arterial: r = 0.355, p = 0.012; venous: r = 0.306, p = 0.026). Increased levels of both arterial and venous TNF-R1 were associated with increased number of lesions on DWI (p = 0.006). In multivariate analysis, venous TNFR1 levels > 1742.2 pg/mL (OR 1.78; 95%CI 1.18-2.67; p = 0.006) and DWI lesions (OR 14.01; 95%CI 1.19-165.3; p = 0.036) were both independent predictors of poor outcome (mRS ≥ 3) at 6 months. CONCLUSION: Increased levels of TNF-R1 in arterial and venous blood correlate with worse cerebral perfusion and with increased burden of acute ischemic lesions in the first 72 h after SAH. Venous levels of TNF-R1 and DWI lesions were associated with poor outcome at 6 months. These results highlight the pathophysiological role of TNF-α pathways in SAH and suggest a possible role of combined imaging and laboratorial markers in determining prognosis in acute SAH.

Brush Sign Is Associated With Increased Severity in Cerebral Venous Thrombosis.

Background and Purpose- The brush sign (BS) is an abnormally accentuated signal drop of the subependymal and deep medullary veins in paramagnetic-sensitive magnetic resonance sequences, previously described in acute ischemic stroke. We aimed to describe the BS in patients with thrombosis of the cerebral veins and sinuses and explore its association with clinical severity, thrombosis extent, parenchymal brain lesion, and clinical prognosis. Methods- We assessed consecutive adult patients admitted to 2 university hospitals with diagnosis of acute thrombosis of the cerebral veins and sinuses and imaging assessment with magnetic resonance imaging, including paramagnetic-sensitive sequences. Demographics, imaging findings, clinical presentation, and functional outcome at 3 months were analyzed according to the presence of BS. Results- In 118 patients included, BS was observed in gradient-echo T2*weighted (T2*WI) in 16% and susceptibility-weighted imaging in 13% of cases. All patients with BS had thrombosis of the superior sagittal sinus, straight sinus, or deep venous system. BS was associated with ipsilateral parenchymal lesion (odds ratio, 6.4; 95% CI, 1.9-21.1; P=0.002) and higher thrombus load (median [interquartile range] 5 [4-6] versus 2 [2-4]); P<0.0001). BS was also associated with focal neurological deficits (OR 4.2; 95%CI, 1.4-12.7, P=0.01). The functional outcome at 3 months was not significantly different in patients with BS. Conclusions- BS in T2*WI and susceptibility-weighted imaging was observed in approximately one in 7 patients with acute thrombosis of the cerebral veins and sinuses. BS was significantly associated with ipsilateral parenchymal brain lesion, extent of thrombosis, and manifestation with focal neurological deficits. This suggests that BS can represent a marker of severity in thrombosis of the cerebral veins and sinuses.

One-Year Risk of Stroke after Transient Ischemic Attack or Minor Stroke.

BACKGROUND: Previous studies conducted between 1997 and 2003 estimated that the risk of stroke or an acute coronary syndrome was 12 to 20% during the first 3 months after a transient ischemic attack (TIA) or minor stroke. The TIAregistry.org project was designed to describe the contemporary profile, etiologic factors, and outcomes in patients with a TIA or minor ischemic stroke who receive care in health systems that now offer urgent evaluation by stroke specialists. METHODS: We recruited patients who had had a TIA or minor stroke within the previous 7 days. Sites were selected if they had systems dedicated to urgent evaluation of patients with TIA. We estimated the 1-year risk of stroke and of the composite outcome of stroke, an acute coronary syndrome, or death from cardiovascular causes. We also examined the association of the ABCD(2) score for the risk of stroke (range, 0 [lowest risk] to 7 [highest risk]), findings on brain imaging, and cause of TIA or minor stroke with the risk of recurrent stroke over a period of 1 year. RESULTS: From 2009 through 2011, we enrolled 4789 patients at 61 sites in 21 countries. A total of 78.4% of the patients were evaluated by stroke specialists within 24 hours after symptom onset. A total of 33.4% of the patients had an acute brain infarction, 23.2% had at least one extracranial or intracranial stenosis of 50% or more, and 10.4% had atrial fibrillation. The Kaplan-Meier estimate of the 1-year event rate of the composite cardiovascular outcome was 6.2% (95% confidence interval, 5.5 to 7.0). Kaplan-Meier estimates of the stroke rate at days 2, 7, 30, 90, and 365 were 1.5%, 2.1%, 2.8%, 3.7%, and 5.1%, respectively. In multivariable analyses, multiple infarctions on brain imaging, large-artery atherosclerosis, and an ABCD(2) score of 6 or 7 were each associated with more than a doubling of the risk of stroke. CONCLUSIONS: We observed a lower risk of cardiovascular events after TIA than previously reported. The ABCD(2) score, findings on brain imaging, and status with respect to large-artery atherosclerosis helped stratify the risk of recurrent stroke within 1 year after a TIA or minor stroke. (Funded by Sanofi and Bristol-Myers Squibb.).

Ischemic Lesions in Acute and Subacute Perimesencephalic Subarachnoid Hemorrhage.

OBJECTIVE: Perimesencephalic hemorrhage (PMH) is a subtype of nonaneurysmal subarachnoid hemorrhage (SAH). In patients with aneurysmal SAH, the occurrence of acute ischemic lesions is associated with severity and poor outcome. We investigated the frequency of ischemic lesions on DWI in patients with PMH and compared it with the frequency of ischemic lesions in patients with aneurysmal SAH. SUBJECTS AND METHODS: From a prospective cohort of 80 patients with acute spontaneous SAH, we included 15 patients with PMH and 39 patients with aneurysmal SAH who were matched on the basis of their clinical condition (World Federation of Neurological Societies grade 1 or 2). MRI was performed less than 72 hours after SAH, 8-10 days after SAH, or at both points in time. The number and distribution of lesions previously seen on DWI that were also seen on a second MRI examination were assessed. Nonparametric tests were used to compare groups. RESULTS: Early acute ischemic lesions (those identified < 72 hours after SAH) were found in 46.2% of patients with PMH and in 62.9% of patients with aneurysmal SAH. No significant differences in the number of acute ischemic lesions between groups were noted less than 72 hours after SAH (median, 0.5 lesion [interquartile range {IQR}, two lesions] in patients with PMH vs one lesion [IQR, three lesions] in patients with aneurysmal SAH [p = 0.48] or 8-10 days after SAH (median, 0.5 lesion [IQR, four lesions] in patients with PMH vs 1.5 lesions [IQR, three lesions] in patients with aneurysmal SAH [p = 0.26]). However, 58.3% of patients with aneurysmal SAH had new infarcts at 8-10 days, compared with 7.1% of patients with PMH. Patients with PMH had diffuse ischemic lesions, whereas patients with aneurysmal SAH in the anterior circulation had mainly supratentorial lesions. CONCLUSION: Early ischemic lesions appeared on DWI both in patients with PMH and in patients with aneurysmal SAH. The number of lesions increased during the time window for vasospasm, mainly in patients with aneurysmal SAH. Further studies are required to better understand the pathophysiologic mechanisms behind early ischemia in patients with PMH and their impact on prognosis.

Imaging predictors of outcome in acute spontaneous subarachnoid hemorrhage: a review of the literature.

Spontaneous subarachnoid hemorrhage (SAH) accounts for about 5% of strokes, but has a very high morbidity and mortality. Many survivors are left with important cognitive impairment and are severely incapacitated. Prediction of complications such as vasospasm and delayed cerebral ischemia, and of clinical outcome after SAH, is challenging. Imaging studies are essential in the initial evaluation of SAH patients and are increasingly relevant in assessing for complications and prognosis. In this article, we reviewed the role of imaging studies in evaluating early brain injury and predicting complications as well as clinical and neuropsychological prognosis after acute SAH.

Venous and arterial TNF-R1 predicts outcome and complications in acute subarachnoid hemorrhage.

BACKGROUND: There is increasing evidence for the role of inflammation in clinical outcome after subarachnoid hemorrhage (SAH). Specifically, the TNF-alfa(α) pathway seems to be relevant after SAH. Although the TNF-α main receptor, TNF-R1 is associated with aneurysm growth and rupture, its relation to prognosis is unknown. We sought to compare TNF-R1 levels in peripheral venous blood and arterial blood closer to the ruptured aneurysm to study the association of TNF-R1 blood levels with poor prognosis (modified Rankin Scale > 2 at discharge, 3 and 6 months) and complications (hydrocephalus or delayed cerebral ischemia/DCI) following SAH. METHODS: We included consecutive SAH patients admitted in the first 72 h of symptoms. Blood samples were simultaneously collected from a peripheral vein and from the main parent artery of the aneurysm. Levels of TNF-R1 were measured using enzyme-linked immunosorbent assays. RESULTS: We analyzed 58 patients. Arterial and venous levels of TNF-R1 were correlated (R = 0.706, p < 0.001). In multivariate regression analysis, venous TNF-R1 was an independent predictor of poor outcome at 6 months after adjusting by age and sex [odds ratio (OR) 11.63; 95% CI 2.09-64.7, p = 0.005] and after adjusting by Glasgow Coma Scale and Fisher scales (OR 8.74; 95% CI 1.45-52.7, p = 0.018). There was no association of TNF-R1 with DCI. A cut-off for arterial TNF-R1 of 1523.7 pg/mL had 75% sensitivity/66% specificity for the prediction of hydrocephalus. CONCLUSION: Levels of venous TNF-R1 are associated with poor outcome in SAH. A specific association was found between levels of arterial TNF-R1 and hydrocephalus. These results are consistent with the role of TNF-α pathway in SAH and need to be validated in larger cohorts.

Etiologic Evaluation of Ischemic Stroke in Young Adults: A Comparative Study between Two European Centers.

INTRODUCTION: Identifying the cause of ischemic stroke in young adults is often difficult. Our objective was to compare the etiologic diagnostic strategy for ischemic stroke in young adults between 2 European centers and investigate the influence of workup variations in the diagnosed etiologies. PATIENTS AND METHODS: We included patients aged 18-55 years admitted for ischemic stroke or transient ischemic attack to the stroke units of Santa Maria Hospital in Lisbon, Portugal, and Innsbruck University Hospital in Innsbruck, Austria, between 2014 and 2016. Etiology and diagnostic procedures were compared between centers. RESULTS: We included 156 patients from Innsbruck University Hospital and 110 patients from Santa Maria Hospital. Search for intracranial large-vessel disease was performed mainly by computed tomography/magnetic resonance angiography in Innsbruck (83.9% versus 52.7%; P < .01) and by transcranial Doppler in Lisbon (91.8% versus 43.2%; P < .01). Transoesophageal echocardiography was preferred in Innsbruck for detecting paradoxical embolism (80.0% versus 68.2%; P < .05), whereas in Lisbon contrast transcranial Doppler was preferred (80.9% versus 3.9%; P < .01). For investigation of other causes, Lisbon patients were more commonly screened for thrombophilia (100.0% versus 92.3%; P < .05) and autoimmune disorders (91.7% versus 44.5%; P < .01) while in Innsbruck consultation by other specialists was more frequent (51.6% versus 10.0%; P < .01). No significant differences were found in etiologies between centers. CONCLUSION: The differences in diagnostic workup did not influence etiologic diagnosis. Extensive laboratory testing does not seem to influence diagnosis of stroke of other determined cause, emphasizing the importance of a clinically-oriented approach for the etiologic diagnosis of stroke in young adults.

Recanalization in Cerebral Venous Thrombosis.

Background and Purpose- The role of recanalization of the occluded dural sinus or vein in the outcome of patients with cerebral venous thrombosis (CVT) is not established. We aimed to systematically review, in patients with CVT, (1) the recanalization rate and its association with (2) clinical outcome and (3) CVT recurrence. Methods- Systematic search in MEDLINE (Medical Literature Analysis and Retrieval System Online), Cochrane Library, and clinicaltrials.gov (inception to September 2017). We considered cohort studies reporting the recanalization rate in adult patients with CVT treated with anticoagulation. Reported rates of venous recanalization at the last follow-up, functional outcome defined using the modified Rankin scale at last follow-up dichotomized for favorable (0-1) and unfavorable (2-6) outcome, and recurrence rate of CVT according to recanalization status were extracted independently by 2 authors. Meta-analyses of proportions were performed using Freeman-Tukey double arcsine transformation. Functional outcomes according to the recanalization status were compared using meta-analysis and ordinal logistic regression. We conducted sensitivity analyses for time to assessment of recanalization and study quality. Results- Four hundred sixty-eight studies were identified, and 19 studies were included. (1) We found report of 694 patients with recanalization in the follow-up among 818 cases of CVT. The overall pooled proportion of patients achieving recanalization was 85% (95% confidence interval, 80-89; I2=58%). In studies with higher methodological quality, the recanalization rate was 77% (95% confidence interval, 70-82; I2=0%). (2) There was a significant increase in the chance of favorable outcome (modified Rankin scale, 0-1) in patients with recanalization with a pooled odds ratio of 3.3 (95% confidence interval, 1.2-8.9; I2=32%) in the random effects meta-analysis and a common odds ratio of 3.3 (95% confidence interval, 1.7-6.3) in the ordinal logistic regression. (3) Data on CVT recurrence according to recanalization was scarce. Conclusions- The overall rate of recanalization in patients receiving anticoagulation was 85%, but exclusion of severe patients from follow-up imaging is a plausible source of bias. Lack of venous recanalization was associated with worse clinical outcome.

Comparison of cerebral perfusion in perimesencephalic subarachnoid hemorrhage and aneurysmal subarachnoid hemorrhage.

PURPOSE: Perimesencephalic hemorrhage (PMH) is a benign subtype of nonaneurysmal subarachnoid hemorrhage (SAH). We aimed to investigate if cerebral perfusion in PMH is less affected than in aneurysmal SAH (aSAH). METHODS: From a prospective cohort of 80 patients with spontaneous SAH, we included PMH patients (n = 15) and selected aSAH patients (n = 39) with similar clinical grade at admission (World Federation of Neurosurgeons Scale-WFNS I/II). Computed tomography (CT) perfusion was performed at < 72 h and/or at 8-10 days. Cerebral perfusion parameter values were compared between groups with nonparametric tests. Subgroup analyses compared PMH and aSAH patients stratified according to aneurysmal location (anterior or posterior circulation) and blood burden (Fisher grade). RESULTS: At < 72 h, no significant differences in perfusion parameters were found between PMH and aSAH patients. At 8-10 days, PMH patients had lower MTT than aSAH patients, and a trend for higher CBF. PMH patients had higher CBF and CBV at < 72 h when compared to posterior circulation aSAH patients. When compared to aSAH patients with similar blood burden, PMH patients had higher CBF and lower MTT at < 72 h, and lower MTT at 8-10 days. CONCLUSION: PMH patients had better cerebral perfusion compared to patients with aSAH, particularly during the vasospasm time window. After stratifying for the amount of blood, PMH patients also had better cerebral perfusion in the first 72 h after SAH. These results are in line with the better clinical presentation and prognosis of PMH, and possibly with a different etiology.

Early Prediction of Delayed Ischemia and Functional Outcome in Acute Subarachnoid Hemorrhage: Role of Diffusion Tensor Imaging.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) parameters are markers of cerebral lesion in some diseases. In patients with acute subarachnoid hemorrhage (SAH), we investigated whether DTI parameters measured at <72 hours might be associated with delayed cerebral ischemia (DCI) and with poor functional outcome at 3 months (modified Rankin Scale score ≥3). METHODS: DTI was performed in a prospective cohort of 60 patients with nontraumatic SAH at <72 hours. Association of fractional anisotropy and apparent diffusion coefficient values at <72 hours with the occurrence of DCI and outcome at 3 months was evaluated with logistic regression models, adjusting for known predictors of prognosis. RESULTS: At <72 hours after SAH, fractional anisotropy values at the cerebellum were associated with DCI occurrence (78% less odds of DCI for each 0.1 increase in fractional anisotropy; P=0.019). Early apparent diffusion coefficient values were not associated with DCI. After adjusting for confounding variables, an increase of 10 U in apparent diffusion coefficient at the frontal centrum semiovale corresponded to 15% increased odds of poor outcome (P=0.061). CONCLUSIONS: DTI parameters at <72 hours post-SAH are independently associated with the occurrence of DCI and functional outcome. These preliminary results suggest the role of DTI parameters as surrogate markers of prognosis in nontraumatic SAH.

Safety of Pregnancy After Cerebral Venous Thrombosis: Results of the ISCVT (International Study on Cerebral Vein and Dural Sinus Thrombosis)-2 PREGNANCY Study.

BACKGROUND AND PURPOSE: Pregnancy is associated with increased risk of venous thrombotic events, including cerebral venous thrombosis. We aimed to study the complications and outcome of subsequent pregnancies in women with previous cerebral venous thrombosis. METHODS: Follow-up study of women with acute cerebral venous thrombosis at childbearing age included in a previously described cohort (International Study of Cerebral Vein and Dural Sinus Thrombosis). Patients were interviewed by local neurologists to assess rate of venous thrombotic events, pregnancy outcomes, and antithrombotic prophylaxis during subsequent pregnancies. RESULTS: A total of 119 women were included, with a median follow-up of 14 years. Eighty-two new pregnancies occurred in 47 women. In 83% (68 of 82), some form of antithrombotic prophylaxis was given during at least 1 trimester of pregnancy or puerperium. Venous thrombotic events occurred in 3 pregnancies, including 1 recurrent cerebral venous thrombosis. Two of the 3 women were on prophylactic low-molecular-weight heparin at the time of the event. Outcomes of pregnancies were 51 full-term newborns, 9 preterm births, 2 stillbirths, and 20 abortions (14 spontaneous). CONCLUSIONS: In women with prior cerebral venous thrombosis, recurrent venous thrombotic events during subsequent pregnancies are infrequent.

Evolution of diffusion tensor imaging parameters after acute subarachnoid haemorrhage: a prospective cohort study.

INTRODUCTION: Few studies assessed diffusion tensor imaging (DTI) changes in the acute phase of subarachnoid haemorrhage (SAH). We prospectively evaluated DTI parameters in the acute phase of SAH and 8-10 days after and analysed whether changes could be related to SAH severity or to the development of delayed cerebral ischemia (DCI). METHODS: Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) changes over time were assessed in a prospective cohort of patients with acute SAH. Two MRI studies were performed at <72 h (MRI-1) and 8-10 days (MRI-2). DTI parameters were recorded in 15 ROIs. Linear mixed regression models were used. RESULTS: Forty-two patients were included. Subtle changes in DTI parameters were found between MRI-1 and MRI-2. At the posterior limb of internal capsule (PLIC), a weak evidence of a 0.02 mean increase in FA (p = 0.064) and a 17.55 × 10-6 mm2/s decrease in ADC (p = 0.052) were found in MRI-2. Both FA and ADC changed over time at the cerebellum (increase of 0.03; p = 0.017; decrease of 34.73 × 10-6 mm2/s; p = 0.002, respectively). Patients with DCI had lower FA values on MRI-1 and lower ADC on MRI-2, although not reaching statistical significance, compared to non-DCI patients. DTI parameters on MRI-1 were not correlated to clinical admission scales. CONCLUSION: ADC and FA values show subtle changes over time in acute SAH at the PLIC and cerebellum although not statistically associated with the severity of SAH or the occurrence of DCI. However, DTI changes occurred mainly in DCI patients, suggesting a possible role of DTI as a marker of DCI.