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.

Endovascular treatment of cerebral sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia.

INTRODUCTION: There is little data on the role of endovascular treatment (EVT) of cerebral venous sinus thrombosis (CVST) due to vaccine-induced immune thrombotic thrombocytopenia (VITT). Here, we describe clinical characteristics and outcomes of CVST-VITT patients who were treated with EVT. PATIENTS AND METHODS: We report data from an international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 6 March 2023. VITT was defined according to the Pavord criteria. RESULTS: EVT was performed in 18/136 (13%) patients with CVST-VITT (92% aspiration and/or stent retrieval, 8% local thrombolysis). Most common indications were extensive thrombosis and clinical or radiological deterioration. Compared to non-EVT patients, those receiving EVT had a higher median thrombus load (4.5 vs 3). Following EVT, local blood flow was improved in 83% (10/12, 95% confidence interval [CI] 54-96). One (6%) asymptomatic sinus perforation occurred. Eight (44%) patients treated with EVT also underwent decompressive surgery. Mortality was 50% (9/18, 95% CI 29-71) and 88% (8/9, 95% CI 25-66) of surviving EVT patients achieved functional independence with a modified Rankin Scale score of 0-2 at follow-up. In multivariable analysis, EVT was not associated with increased mortality (adjusted odds ratio, 0.66, 95% CI 0.16-2.58). DISCUSSION AND CONCLUSION: We describe the largest cohort of CVST-VITT patients receiving EVT. Half of the patients receiving EVT died during hospital admission, but most survivors achieved functional independence.

Sex differences in cerebral venous sinus thrombosis after adenoviral vaccination against COVID-19.

INTRODUCTION: Cerebral venous sinus thrombosis associated with vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is a severe disease with high mortality. There are few data on sex differences in CVST-VITT. The aim of our study was to investigate the differences in presentation, treatment, clinical course, complications, and outcome of CVST-VITT between women and men. PATIENTS AND METHODS: We used data from an ongoing international registry on CVST-VITT. VITT was diagnosed according to the Pavord criteria. We compared the characteristics of CVST-VITT in women and men. RESULTS: Of 133 patients with possible, probable, or definite CVST-VITT, 102 (77%) were women. Women were slightly younger [median age 42 (IQR 28-54) vs 45 (28-56)], presented more often with coma (26% vs 10%) and had a lower platelet count at presentation [median (IQR) 50x109/L (28-79) vs 68 (30-125)] than men. The nadir platelet count was lower in women [median (IQR) 34 (19-62) vs 53 (20-92)]. More women received endovascular treatment than men (15% vs 6%). Rates of treatment with intravenous immunoglobulins were similar (63% vs 66%), as were new venous thromboembolic events (14% vs 14%) and major bleeding complications (30% vs 20%). Rates of good functional outcome (modified Rankin Scale 0-2, 42% vs 45%) and in-hospital death (39% vs 41%) did not differ. DISCUSSION AND CONCLUSIONS: Three quarters of CVST-VITT patients in this study were women. Women were more severely affected at presentation, but clinical course and outcome did not differ between women and men. VITT-specific treatments were overall similar, but more women received endovascular treatment.

Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia in middle-income countries.

BACKGROUND: Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). Remarkably, cases of cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) have rarely been reported from LMICs. AIMS: We studied the frequency, manifestations, treatment, and outcomes of CVST-VITT in LMICs. METHODS: We report data from an international registry on CVST after COVID-19 vaccination. VITT was classified according to the Pavord criteria. We compared CVST-VITT cases from LMICs to cases from high-income countries (HICs). RESULTS: Until August 2022, 228 CVST cases were reported, of which 63 were from LMICs (all middle-income countries [MICs]: Brazil, China, India, Iran, Mexico, Pakistan, Turkey). Of these 63, 32 (51%) met the VITT criteria, compared to 103 of 165 (62%) from HICs. Only 5 of the 32 (16%) CVST-VITT cases from MICs had definite VITT, mostly because anti-platelet factor 4 antibodies were often not tested. The median age was 26 (interquartile range [IQR] 20-37) versus 47 (IQR 32-58) years, and the proportion of women was 25 of 32 (78%) versus 77 of 103 (75%) in MICs versus HICs, respectively. Patients from MICs were diagnosed later than patients from HICs (1/32 [3%] vs. 65/103 [63%] diagnosed before May 2021). Clinical manifestations, including intracranial hemorrhage, were largely similar as was intravenous immunoglobulin use. In-hospital mortality was lower in MICs (7/31 [23%, 95% confidence interval (CI) 11-40]) than in HICs (44/102 [43%, 95% CI 34-53], p = 0.039). CONCLUSIONS: The number of CVST-VITT cases reported from LMICs was small despite the widespread use of adenoviral vaccines. Clinical manifestations and treatment of CVST-VITT cases were largely similar in MICs and HICs, while mortality was lower in patients from MICs.

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.

Decompressive surgery in cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia.

BACKGROUND AND PURPOSE: Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is an adverse drug reaction occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. CVST-VITT patients often present with large intracerebral haemorrhages and a high proportion undergoes decompressive surgery. Clinical characteristics, therapeutic management and outcomes of CVST-VITT patients who underwent decompressive surgery are described and predictors of in-hospital mortality in these patients are explored. METHODS: Data from an ongoing international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 10 May 2022, were used. Definite, probable and possible VITT cases, as defined by Pavord et al. (N Engl J Med 2021; 385: 1680-1689), were included. RESULTS: Decompressive surgery was performed in 34/128 (27%) patients with CVST-VITT. In-hospital mortality was 22/34 (65%) in the surgical and 27/94 (29%) in the non-surgical group (p < 0.001). In all surgical cases, the cause of death was brain herniation. The highest mortality rates were found amongst patients with preoperative coma (17/18, 94% vs. 4/14, 29% in the non-comatose; p < 0.001) and bilaterally absent pupillary reflexes (7/7, 100% vs. 6/9, 67% with unilaterally reactive pupil, and 4/11, 36% with bilaterally reactive pupils; p = 0.023). Postoperative imaging revealed worsening of index haemorrhagic lesion in 19 (70%) patients and new haemorrhagic lesions in 16 (59%) patients. At a median follow-up of 6 months, 8/10 of surgical CVST-VITT who survived admission were functionally independent. CONCLUSIONS: Almost two-thirds of surgical CVST-VITT patients died during hospital admission. Preoperative coma and bilateral absence of pupillary responses were associated with higher mortality rates. Survivors often achieved functional independence.

Incidence of Guillain-Barré syndrome following SARS-CoV-2 immunization: Analysis of a nationwide registry of recipients of 81 million doses of seven vaccines.

BACKGROUND AND PURPOSE: Information on Guillain-Barré syndrome (GBS) as an adverse event following immunization (AEFI) against SARS-CoV-2 remains scarce. We aimed to report GBS incidence as an AEFI among adult (≥18 years) recipients of 81,842,426 doses of seven anti-SARS-CoV-2 vaccines between December 24, 2020, and October 29, 2021, in Mexico. METHODS: Cases were retrospectively collected through passive epidemiological surveillance. The overall observed incidence was calculated according to the total number of administered doses. Vaccines were analyzed individually and by vector as mRNA-based (mRNA-1273 and BNT162b2), adenovirus-vectored (ChAdOx1 nCov-19, rAd26-rAd5, Ad5-nCoV, and Ad26.COV2-S), and inactivated whole-virion-vectored (CoronaVac) vaccines. RESULTS: We identified 97 patients (52 males [53.6%]; median [interquartile range] age 44 [33-60] years), for an overall observed incidence of 1.19/1,000,000 doses (95% confidence interval [CI] 0.97-1.45), with incidence higher among Ad26.COV2-S (3.86/1,000,000 doses, 95% CI 1.50-9.93) and BNT162b2 recipients (1.92/1,00,000 doses, 95% CI 1.36-2.71). The interval (interquartile range) from vaccination to GBS symptom onset was 10 (3-17) days. Preceding diarrhea was reported in 21 patients (21.6%) and mild COVID-19 in four more (4.1%). Only 18 patients were tested for Campylobacter jejuni (positive in 16 [88.9%]). Electrophysiological examinations were performed in 76 patients (78.4%; axonal in 46 [60.5%] and demyelinating in 25 [32.8%]); variants were similar across the platforms. On admission, 91.8% had a GBS disability score ≥3. Seventy-five patients (77.3%) received intravenous immunoglobulin, received seven plasma exchange (7.2%), and 15 (15.5%) were treated conservatively. Ten patients (10.3%) died, and 79.1% of survivors were unable to walk independently. CONCLUSIONS: Guillain-Barré syndrome was an extremely infrequent AEFI against SARS-CoV-2. The protection provided by these vaccines outweighs the risk of developing GBS.

Evaluating Rates of Recurrent Ischemic Stroke Among Young Adults With Embolic Stroke of Undetermined Source: The Young ESUS Longitudinal Cohort Study.

Importance: Cryptogenic strokes constitute approximately 40% of ischemic strokes in young adults, and most meet criteria for the embolic stroke of undetermined source (ESUS). Two randomized clinical trials, NAVIGATE ESUS and RESPECT ESUS, showed a high rate of stroke recurrence in older adults with ESUS but the prognosis and prognostic factors among younger individuals with ESUS is uncertain. Objective: To determine rates of and factors associated with recurrent ischemic stroke and death and new-onset atrial fibrillation (AF) among young adults. Design, Setting, and Participants: This multicenter longitudinal cohort study with enrollment from October 2017 to October 2019 and a mean follow-up period of 12 months ending in October 2020 included 41 stroke research centers in 13 countries. Consecutive patients 50 years and younger with a diagnosis of ESUS were included. Of 576 screened, 535 participants were enrolled after 1 withdrew consent, 41 were found to be ineligible, and 2 were excluded for other reasons. The final follow-up visit was completed by 520 patients. Main Outcomes and Measures: Recurrent ischemic stroke and/or death, recurrent ischemic stroke, and prevalence of patent foramen ovale (PFO). Results: The mean (SD) age of participants was 40.4 (7.3) years, and 297 (56%) participants were male. The most frequent vascular risk factors were tobacco use (240 patients [45%]), hypertension (118 patients [22%]), and dyslipidemia (109 patients [20%]). PFO was detected in 177 participants (50%) who had transthoracic echocardiograms with bubble studies. Following initial ESUS, 468 participants (88%) were receiving antiplatelet therapy, and 52 (10%) received anticoagulation. The recurrent ischemic stroke and death rate was 2.19 per 100 patient-years, and the ischemic stroke recurrence rate was 1.9 per 100 patient-years. Of the recurrent strokes, 9 (64%) were ESUS, 2 (14%) were cardioembolic, and 3 (21%) were of other determined cause. AF was detected in 15 participants (2.8%; 95% CI, 1.6-4.6). In multivariate analysis, the following were associated with recurrent ischemic stroke: history of stroke or transient ischemic attack (hazard ratio, 5.3; 95% CI, 1.8-15), presence of diabetes (hazard ratio, 4.4; 95% CI, 1.5-13), and history of coronary artery disease (hazard ratio, 10; 95% CI, 4.8-22). Conclusions and Relevance: In this large cohort of young adult patients with ESUS, there was a relatively low rate of subsequent ischemic stroke and a low frequency of new-onset AF. Most recurrent strokes also met the criteria for ESUS, suggesting the need for future studies to improve our understanding of the underlying stroke mechanism in this population.

The role of left atrial enlargement and age in the prediction of recurrence in embolic strokes of undetermined source / El papel del crecimiento auricular izquierdo y la edad como predictores de recurrencia en infarto cerebral embólicos de origen indeterminado

Abstract Objectives: Left atrial disease is an independent risk factor for ischemic stroke and can be used to predict atrial fibrillation (AF). We examine whether left atrial enlargement (LAE) could predict stroke recurrence in patients with embolic stroke of undetermined source (ESUS). Materials and methods: Sixty-four patients with a confirmed diagnosis of ESUS were followed for a median of 22 months. Clinical data and echocardiogram findings were recorded. The echocardiogram interpretation was performed centrally and blindly. The Brown ESUS – AF score was used to categorize patients into high (human resource planning [HRP]: score > 2) and low-risk patients (non-HRP score 0-1). Stroke recurrence was the primary outcome. Results: The median age was 62 years (range: 22-85 years); and 33 (51.6%) were men. The median initial NIHSS score was three points (range: 0-27). Twelve (18.8%) patients were categorized as HRP. We found a significant tendency toward recurrence among HRP versus non-HRP patients. Three (25%) HRP versus 2 (3.8%) non-HRP experienced recurrence (OR: 8.3 95% CI 1.2-57; p=0.042); this association was related to severe atrial dilatation (OR: 14.5 95% CI 0.78-277, p = 0.02) and age > 75 years (OR: 12.7 95% CI 1.7-92.2, p = 0.03). We found no differences in recurrence in a univariate analysis. Conclusions: Patients with severe LAE who are 75 years old or older have a significant tendency to experience stroke recurrence.

Resumen Objetivos: La patología atrial izquierda es factor de riesgo independiente para infarto cerebral y puede utilizarse para predecir fibrilación auricular. Examinamos si el crecimiento aurícular izquierdo puede predecir recurrencia en pacientes con infarto embolico de origen indeterminado (ESUS). Materiales y métodos: Sesenta y cuatro pacientes con diagnóstico confirmado de ESUS fueron seguidos por una mediana de seguimiento de 22 meses. Registramos los datos clínicos y ecocardiográficos. La interpretación ecocardiográfica fue centralizada y cegada. La escala de Brown ESUS – AF fue utilizada para categorizar a los pacientes en riesgo alto (HRP puntaje > 2) y bajo riesgo (no-HRP: puntaje 0-1). El descenlace primario fue recurrencia de infarto cerebral. Resultados: Mediana de edad fue de 62 años (rango: 22-85 años); 33 (51.6%) fueron hombres. La mediana inicial de la escala de NIHSS fue de 3 putnos (rango de 0 a 27). 12 (18.8%) pacientes fueron de alto riesgo (HRP) y 52 (81.3%) de bajo riesgo (non- HRP). El grupo HRP mostró tendencia significatica hacia mayor recurrencia. Tres (25%) HRP versus 2 (3.8%) no-HRP experimentaron recurrencia (OR: 8.3 IC 95% 1.2-57; p = 0.042); esta asociación se relacionó con dilatación auricular severa (OR: 14.5 IC 95% 0.78-277, p = 0.02) y edad > 75 años (OR: 12.7 IC 95% 1.7-92.2, p = 0.03). En el análisis multivarioado, no encontramos significativas. Conclusiones: El crecimiento auricular izquierdo severo y la edad mayor de 75 años mostraron tendencia significativa a recurrencia de infarto cerebral.

Bilateral Decompressive Craniectomy in Malignant Cerebral Venous Thrombosis.

INTRODUCTION: Despite the extremely favourable prognosis of patients with cerebral venous thrombosis (CVT), death occurs in 10-15% of patients. In severe cases of malignant CVT with supratentorial haemorrhagic lesions, cerebral oedema and brain herniation, decompressive surgery may be the only life-saving treatment. PATIENT AND METHODS: We present the case of a puerperal young woman with progressive headache, seizures and decreased alertness. Thrombosis of the entire superior sagittal sinus with bifrontal venous infarcts and midline shift was confirmed by magnetic resonance imaging with venography sequencing. Despite medical treatment with anticoagulation, progressive neurological deterioration was observed, so bilateral, frontal decompressive craniectomy was performed. RESULTS: At the 6-month follow-up, we observed partial functional recovery with a modified Rankin score of 3. DISCUSSION: Bilateral decompressive craniectomy may be a life-saving therapeutic option when medical therapy fails and there are clinical and radiological features of progression in both cerebral hemispheres. LEARNING POINTS: Malignant cerebral venous thrombosis presents with diffuse haemorrhagic lesions or cerebral oedema associated with brain herniation and rapid clinical deterioration.Decompressive surgery may be the only life-saving treatment in severe cases.Early and adequate intervention based on the characteristics of the lesions allowed preservation of life and improvement in long-term functionality.

Characterization of Patients with Embolic Strokes of Undetermined Source in the NAVIGATE ESUS Randomized Trial.

BACKGROUND: The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial is a randomized phase-III trial comparing rivaroxaban versus aspirin in patients with recent ESUS. AIMS: We aimed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups. METHODS: We enrolled 7213 patients at 459 sites in 31 countries. Prespecified subgroups for primary safety and efficacy analyses included age, sex, race, global region, stroke or transient ischemic attack prior to qualifying event, time to randomization, hypertension, and diabetes mellitus. RESULTS: Mean age was 66.9 ± 9.8 years; 24% were under 60 years. Older patients had more hypertension, coronary disease, and cancer. Strokes in older subjects were more frequently cortical and accompanied by radiographic evidence of prior infarction. Women comprised 38% of participants and were older than men. Patients from East Asia were oldest whereas those from Latin America were youngest. Patients in the Americas more frequently were on aspirin prior to the qualifying stroke. Acute cortical infarction was more common in the United States, Canada, and Western Europe, whereas prior radiographic infarctions were most common in East Asia. Approximately forty-five percent of subjects were enrolled within 30 days of the qualifying stroke, with earliest enrollments in Asia and Eastern Europe. CONCLUSIONS: NAVIGATE-ESUS is the largest randomized trial comparing antithrombotic strategies for secondary stroke prevention in patients with ESUS. The study population encompasses a broad array of patients across multiple continents and these subgroups provide ample opportunities for future research.

Risk Factors for Unfavorable Outcomes in Surgically Treated Brainstem Cavernous Malformations.

OBJECTIVE: Brainstem cavernous malformations (BSCMs) account for up to 18% of all intracranial cavernous malformations. Due to their complex anatomic location, they represent a significant challenge for neurosurgeons. As such, the identification of risk factors associated with negative outcomes is of significant importance. We analyze a series of 50 cases of BSCMs treated surgically in order to identify risk factors for unfavorable outcomes. METHODS: Patients who underwent surgical resection of BSCM at our institution between 2000 and 2015 were retrospectively reviewed. Univariate and multivariable logistic regression models were used to identify predictors of unfavorable outcomes, defined as those with a modified Rankin score (mRs) of >2. RESULTS: Fifty Latin American patients, with a mean age of 35.85 ± 13.06 years, consisting of 29 females (58%) and 21 males (42%), underwent surgical resection. Mean modified Rankin Scale (mRs) score at admission was 2.6 ± 1.05, and the mean BCSM size was 18.00 ± 7.19 mm. The rate of gross total resection was 92%. Overall, 80% of patients showed improved or unchanged clinical status at the last follow-up period; however, only 58% of patients had a favorable outcome with a mean mRs of 2.33 ± 1.136. Multivariable logistic binary regression identified hemorrhagic recurrence (P = 0.040), lower cranial nerve deficit (P = 0.019), and BSCMs >15 mm in diameter (P = 0.006) as predictive factors for unfavorable surgical outcomes. CONCLUSION: BSCM size, compromise of lower cranial nerves, and hemorrhagic recurrence before surgery were identified as risk factors associated with unfavorable outcomes of surgically treated BSCMs in this cohort.

Rebleeding and Outcome in Patients with Symptomatic Brain Stem Cavernomas.

PURPOSE: We sought to evaluate the long-term functional outcomes and identify the potential risk factors for rebleeding in patients with brain stem cavernous malformations (BCMs) who presented with hemorrhages and were surgically or conservatively treated and prospectively monitored. METHODS: From January 1990 to July 2015, we included patients with first hemorrhagic episodes secondary to single BCMs. Modified Rankin score (mRS) was used for neurological status assessment. Univariate and multivariate regression statistics were used to identify the risk factors for rebleeding. RESULTS: A total of 99 patients with BCMs hemorrhages were included (59 [59.6%] women, mean age 37± 13 years). As initial treatments, 37 patients (37.4%) underwent surgery and 62 (62.6%) received conservative treatment. The median follow-up was 3.33 years (interquartile range 1.16-7 years; 408.3 patient/years). The rebleeding rate by patient/year was 10% in conservatively treated patients. Deterioration was significantly more frequent in patients with rebleeding (p = 0.0001). At the end of the follow-up, the mRS were favorable in 49 patients (65.3%) without rebleeding, whereas only 8 (33.3%) with rebleeding evolved to favorable outcomes (p = 0.006). Lesion size >18 mm (hazards ratio, HR 3.34, 95% CI 1.54-7.26; p = 0.0001) and ventral location or crossing the brain stem's midpoint (HR 2.5, 95% CI 1.14-5.46; p = 0.022) were associated with a major risk of rebleeding in the univariate analysis, but only a lesion >18 mm remained statistically significant (HR 2.7, 95% CI 1.2-6.21; p = 0.016) in the multivariate analysis. CONCLUSION: A lesion size >18 mm was the principal factor associated with hemorrhage recurrence. The overall functional outcome was good. However, significant morbidity was attributable to rebleeding.

Morphological classification of penetrating artery pontine infarcts and association with risk factors and prognosis: The SPS3 trial.

BACKGROUND: Pontine infarcts are common and often attributed to small vessel disease ("small deep infarcts") or basilar branch atherosclerosis ("wedge shaped"). A well-described morphological differentiation using magnetic resonance images has not been reported. Furthermore, whether risk factors and outcomes differ by morphology, or whether infarct morphology should guide secondary prevention strategy, is not well characterized. METHODS: All participants in the Secondary Prevention of Small Subcortical Strokes Study with magnetic resonance imaging -proven pontine infarcts were included. Infarcts were classified as well-circumscribed small deep (small deep infarct, i.e. lacunar), paramedian, atypical paramedian, or other based on diffusion-weighted imaging, T2/fluid-attenuated inversion recovery, and T1-magnetic resonance images. Inter-rater reliability was high (90% agreement, Cohen's kappa = 0.84). Clinical and radiologic features independently associated with small deep infarct versus paramedian infarcts were identified (multivariable logistic regression). Differences in stroke risk and death were assessed using Cox proportional hazards. RESULTS: Of the 3020 patients enrolled, 644 had pontine infarcts; 619 images were available: 302(49%) small deep infarct, 245 (40%) paramedian wedge, 35 (6%) atypical paramedian, and 37 (6%) other. Among vascular risk factors, only smoking (OR 2.1, 95% CI 1.3-3.3) was independently associated with small deep infarct versus paramedian infarcts; on neuroimaging, old lacunes on T1/fluid-attenuated inversion recovery (OR 1.8, 1.3-2.6) and intracranial stenosis (any location) ≥50% (OR 0.62, 0.41-0.96). Small deep infarct versus paramedian was not predictive of either recurrent stroke or death, and there was no interaction with assigned treatment. CONCLUSIONS: Pontine infarcts can be reliably classified based on morphology using clinical magnetic resonance images. Few risk factors differed between small deep infarct and paramedian infarcts with no differences in recurrent stroke or mortality. There was no difference in response to different antiplatelet or blood pressure treatment strategies between these two groups. REGISTRATION: http://www.clinicaltrials.gov/NCT00059306.

Multiple hereditary exostoses and stroke due to vertebral artery dissection.

UNLABELLED: Vascular complications related to multiple hereditary exostoses are uncommon. We present a 39-year-old male patient with multiple exostoses in the upper and lower limbs with an associated positive familial history of such lesions. He experienced a sudden onset of left-side ataxia and hypoesthesia secondary to a left lateral medullary infarction, which was due to a stenotic-pattern vertebral artery dissection (V1-V4). This complication is very rare as a differential diagnosis in the vertebro-basilar dissection spectrum, and a nonspecific relation has been found. ABBREVIATIONS: MHEMultiple hereditary exostosesATangiotomographyVADvertebral artery dissectionCADcervical artery dissectionOIosteogenesis imperfecta.

Alteraciones neuropsicológicas asociadas en pacientes con infarto lacunar / Neuropsychological disorders associated with patients with lacunar infarct / Alterações neuropsicológicas associadas em pacientes com enfarte lacunar

Existe poca evidencia del deterioro cognoscitivo que defina el perfil del paciente con Infarto Lacunar (IL). El propósito de este estudio fue identificar las alteraciones neuropsicológicas en este tipo de pacientes. La muestra estuvo compuesta por 16 pacientes con IL y 16 participantes sanos con una edad promedio de 63 ± 9.41 y 64.75 ± 9.06 años y una escolaridad de 7.55 ± 4.34 y 7.94 ± 3.51, respectivamente. Se valoró la función cognoscitiva mediante un instrumento de tamizaje y una batería neuropsicológica. El análisis estadístico se llevó a cabo a través de la prueba Kruskal-Wallis y la U de Man-Whitney. Los pacientes con IL se caracterizan por la alteración de dominios como planeación, fluidez verbal, cambio atencional, habilidad visoconstructiva y velocidad de procesamiento de la información (p < 0.050). El IL se relaciona con el deterioro del funcionamiento ejecutivo y de velocidad de procesamiento, debido a la interrupción de circuitos frontocortico-subcorticales asociados con su correcto desempeño.

There is little evidence of cognitive impairment to define the profile of patients with Lacunar Infarction (IL). The purpose of this study was to identify the neuropsychological disorders in these patients. The sample consisted of 16 patients with IL and 16 healthy control participants with an average age of 63 ± 9.41 and 64.75 ± 9.06 years, and average schooling of 7.55 ± 4.34 and 7.94 ± 3.51, respectively. Cognitive function was assessed using a screening tool and a neuropsychological battery. Statistical analysis was carried out by the Kruskal-Wallis and Mann-Whitney U tests. Patients with IL are characterized by the alteration of domains such as planning, verbal fluency, attention switching, visoconstructive skill and information processing speed (p <0.050). The IL is related to the impairment of executive functioning and processing speed, due to the interruption of frontocortico-subcortical circuits associated with their proper performance.

Existe pouca evidência da deterioração cognoscitiva que defina o perfil do paciente com Enfarte Lacunar (IL). O propósito deste estudo foi identificar as alterações neuropsicológicas neste tipo de pacientes. A mostra foi composta por 16 pacientes com IL e 16 participantes sãos com uma idade média de 63 ± 9.41 e 64.75 ± 9.06 anos e uma escolaridade de 7.55 ± 4.34 e 7.94 ± 3.51, respectivamente. Avaliou-se a função cognoscitiva mediante um instrumento de tamizagem e uma bateria neuropsicológica. A análise estadística foi feita através do teste Kruskal-Wallis e a U de Man-Whitney. Os pacientes com IL se caracterizan pela alteração de dominios como planejamento, fluêcia verbal, mudança atencional, habilidade visoconstructiva e velocidade de processamento da informação (p < 0.050). O IL se relaciona com a deterioração do funcionamento executivo e da velocidade de processamento, devido à interrupção de circuitos frontocortico-subcorticais associados com seu correto desempenho.

Vascular cognitive disorders and depression after first-ever stroke: the Fogarty-Mexico Stroke Cohort.

BACKGROUND AND PURPOSE: Stroke is the major cause of vascular behavior and cognitive disorders worldwide. In developing countries, there is a dearth of information regarding the public health magnitude of stroke. The aim of the Fogarty-Mexico cohort was to assess the prevalence of vascular behavioral and cognitive disorders, ranging from mild vascular cognitive impairment (VCI) to vascular dementia (VaD), in a cohort of acute first-ever symptomatic stroke patients in Mexico. METHODS: A total of 165 consecutive, first-ever stroke patients admitted to the National Institute of Neurology and Neurosurgery in Mexico City, were included in the cohort. Patients were eligible if they had an ischemic stroke, primary intracerebral hemorrhage, or cerebral venous thrombosis (CVT). Stroke diagnosis required the presence of an acute focal deficit lasting more than 24 h, confirmed by a corresponding lesion on CT/MRI. Stroke severity was established with the NIH Stroke Scale. The pre-stroke functional status was determined by the IQCODE. Three months after the occurrence of stroke, 110 survivor patients returned for follow-up and were able to undergo functional outcome (modified Rankin scale, Barthel index), along with neurological, psychiatric, neuropsychological, laboratory, and imaging assessments. We compared depression, demographic, and clinical and imaging features between patients with and without dementia, and between patients with VCI and those with intact cognition. RESULTS: Of the 110 patients (62% men, mean age 56 ± 17.8, education 7.7 ± 5.2 years) 93 (84%) had ischemic strokes, 14 (13%) intracerebral hemorrhage, and 3 (3%) CVT. The main risk factors were hypertension (50%), smoking (40%), hypercholesterolemia (29%), hyperhomocysteinemia (24%), and diabetes (22%). Clinical and neuropsychological evaluations demonstrated post-stroke depression in 56%, VCI in 41%, and VaD in 12%; 17% of the latter had pre-stroke functional impairment (IQCODE >3.5). Cognitive deficits included executive function in 69%, verbal memory in 49%, language in 38%, perception in 36%, and attention in 38%. Executive dysfunction occurred in 36% of non-demented subjects, 65% of them with mild-moderate deficits in daily living activities. Female gender (p ≤ 0.054), older age (mean age 65.6 years vs. 49.3, p < 0.001), diabetes (p ≤ 0.004), illiteracy and lower education (p ≤ 0.001), and PSD (p = 0.03) were significantly higher in VCI-VaD compared with cognitively intact post-stroke subjects. We could not demonstrate an association with lesion site and distribution of the cognitive deficits. CONCLUSIONS: The Fogarty-Mexico cohort recruited relatively young acute stroke patients, compared with other Mexican stroke cohorts. PSD and VCI occurred frequently but prevalence of VaD (12%) was lower than expected. A high prevalence of treatable stroke risk factors suggests that preventive interventions are advisable.