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Copyright © 2018 World Stroke Organization, Rationale: After a cerebral vein thrombosis, there is an increased risk of further venous thromboembolic events. The optimal duration of anticoagulation after cerebral vein thrombosis is unknown. Aim: To compare efficacy and safety of a policy of short- (3–6 months) versus long-term (12 months) anticoagulation (any type venous thromboembolic events) after cerebral vein thrombosis for the prevention of venous thromboembolic events. Sample size estimates: A sample of 1428 patients (749 per arm) allows detecting a reduction from 10 to 5% in the risk of venous thromboembolic event recurrence with 80% power at 5% significance, with 3% dropout rate. Methods and design: An international multicenter, prospective cluster-randomized trial with equal allocation between both interventions (ISRCTN25644448). Each cluster is a participating center, which accepted to be randomly allocated to one of the anticoagulation policies. Eligible patients are adults with radiologically confirmed cerebral vein thrombosis within 30 days, and stable to initiate post-acute anticoagulation. Patients judged by the investigator to be an absolute indication for permanent anticoagulation are excluded. Follow-up is at 6, 12 and 24 months. Study outcomes: Primary efficacy outcome is any symptomatic and confirmed fatal/nonfatal venous thromboembolic event (recurrent-cerebral vein thrombosis or non-cerebral venous thromboembolic event). Primary safety outcomes include bleeding events during treatment periods and death from any cause. Discussion: This study responds to a knowledge gap in the post-acute management of cerebral vein thrombosis patients by comparing short- versus long-term anticoagulation for the prevention of venous thromboembolic event recurrence.

Background and Aims Mortality and bad outcome by stroke are higher in developing countries than in industrialized countries. Health-care system efficiency could explain these disparities. Our objective was to identify the impact on short- and middle-term outcomes of patients with acute ischemic stroke (AIS) among public and private Mexican medical care. Methods We analyzed data from patients with AIS included in the Primer Registro Mexicano de Isquemia Cerebral (PREMIER) study. Transient ischemic attacks (TIAs) and ambulatory patients were excluded. Mortality and good outcome were assessed by the modified Rankin Scale (mRS) and analyzed at 1, 3, and 12 months of follow-up. Results From 1246 patients with AIS included in the registry, 1123 were hospitalized, either in public (n = 881) or in private (n = 242) hospitals. There were no significant differences regarding age and gender. In private settings, patients had a higher educational level, a major frequency of dyslipidemia, a previous stroke and TIA, less overweight and obesity, a sedentary lifestyle, and diabetes; stroke severity, the rate of systemic complications, the length of stay, and in-hospital mortality were also lower; a major frequency of thrombolysis was observed when compared with public hospitals. Our study showed a better outcome (mRS score ≤2) in private scenarios and a higher mortality in patients treated in public hospitals at short- and middle-term follow-ups. Conclusions A polarized medical practice was observed in the AIS care in this large multicenter cohort of Mexico. There is evidence of an advantage for private scenarios, possibly related with an optimal infrastructure or with a strong patient's economic status.

Background/Aims: To evaluate the relationship between hippocampal volume and cognitive decline in patients with dementia due to probable Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI) and education, and the possible relationship between cognitive reserve and education in this population. Methods: From February 2013 to October 2015, 76 patients (25 men, 51 women) were classified according to the NIA-AA diagnostic criteria. We used two 3.0-tesla MRI scanners and performed manual hippocampal volumetry. Results: Twenty-six patients were found to have AD, 20 aMCI and 30 had normal aging (NA). The mean normalized hippocampal volume in age-, sex- and education (years)-matched subjects was 2.38 ± 0.51 cm3 in AD (p < 0.001), 2.91 ± 0.78 cm3 in aMCI (p = 0.019) and 3.07 ± 0.76 cm3 in NA. Conclusion: Psychometric test (MMSE and MoCA) scores had a good to strong positive correlation with statistically significant differences in the entire population and healthy subjects but not among dementia patients and lower educational level groups. The patients with low education had greater hippocampal volumes, which is in line with the cognitive reserve theory; lower-educated individuals can tolerate less neuropathology and will thus show less atrophy at a similar level of cognitive performance than higher-educated subjects.

Background and Purpose— Local infections of the head or neck are a cause of cerebral venous thrombosis. Treatment of infectious cerebral venous thrombosis with heparin is controversial. We examined whether this treatment was associated with intracranial hemorrhagic complications and poor clinical outcome. Methods— We retrieved data from a prospective cohort study of 624 cerebral venous thrombosis patients. We compared patients with and without an infection of the head or neck and anticoagulated versus not anticoagulated. We examined death or dependency and new intracerebral hemorrhages. Results— Six hundred four of 624 patients were eligible for the study. Fifty-seven patients had an infection of the head or neck (9.4%). Comparing data between infection and noninfection patients, the frequency of therapeutic doses of heparin was similar in both groups (82.5% versus 83.7%). New intracerebral hemorrhages were more common in patients with an infection (12.3% versus 5.3%; P =0.04), but death or dependency did not differ between patients with and without an infection (15.8% versus 13.7%). In patients with an infection of the head or neck, there was no significant difference in the frequency of new intracerebral hemorrhages and poor outcome between patients who did or did not receive therapeutic doses of heparin. Conclusions— New intracerebral hemorrhages were more frequent in patients with an infection. The use of therapeutic doses of heparin did not seem to influence the risk of new intracranial hemorrhages or poor clinical outcome, but the number of patients who did not receive anticoagulation was too small to draw firm conclusions about safety of heparin in adults with cerebral venous thrombosis and an infection of the head or neck.

Summary Cerebral venous thrombosis (CVT) is a relatively rare form of stroke usually affecting young individuals. CVT is characterized by the diversity of its neurologic manifestations, which require a high level of clinical suspicion for diagnosis and prompt, appropriate treatment. Multiple circumstances have been associated with CVT, such as prior medical conditions, transient situations, certain medications, and some predisposing conditions. Headache, focal neurologic deficit, and seizures are the most frequent clinical manifestations at onset. MRI in combination with venography has become the imaging modality of choice, as this technique has a high sensitivity and specificity for establishing a diagnosis. CT venography is an alternative to MRI because this technique produces similar diagnostic results. Pharmacologic treatment of CVT with anticoagulants is widely accepted. Per 100 cases, the recurrence of CVT is 2.8% and the mortality of CVT is 10%.

Introduction: Information regarding hospital arrival times after acute ischaemic stroke (AIS) has mainly been gathered from countries with specialised stroke units. Little data from emerging nations are available. We aim to identify factors associated with achieving hospital arrival times of less than 1, 3, and 6 hours, and analyse how arrival times are related to functional outcomes after AIS. Methods: We analysed data from patients with AIS included in the PREMIER study (Primer Registro Mexicano de Isquemia Cerebral) which defined time from symptom onset to hospital arrival. The functional prognosis at 30 days and at 3, 6, and 12 months was evaluated using the modified Rankin Scale. Results: Among 1096 patients with AIS, 61 (6%) arrived in

Resumen: Introducción: La información sobre el tiempo de llegada hospitalaria después de un infarto cerebral (IC) se ha originado en países con unidades especializadas en ictus. Existe poca información en naciones emergentes. Nos propusimos identificar los factores que influyen en el tiempo de llegada hospitalaria a 1, 3 y 6 h y su relación con el pronóstico funcional después del ictus. Métodos: Se analizó la información de pacientes con IC incluidos en el estudio Primer Registro Mexicano de Isquemia Cerebral (PREMIER) que tuvieran tiempo definido desde el inicio de los síntomas hasta la llegada hospitalaria. El desenlace funcional se evaluó mediante la escala modificada de Rankin a los 30 días, 3, 6 y 12 meses. Resultados: De 1.096 pacientes con IC, 61 (6%) llegaron en < 1 h, 250 (23%) en < 3 h y 464 (42%) en < 6 h. Favorecieron la llegada temprana en < 1 h: el antecedente familiar de cardiopatía isquémica y ser migrañoso; en < 3 h: edad 40-69 años, antecedente familiar de hipertensión, antecedente personal de dislipidemia y cardiopatía isquémica, así como la atención en hospital privado; en < 6 h: antecedente familiar de hipertensión, ser migrañoso, ictus previo, cardiopatía isquémica y atención en hospital privado. La llegada hospitalaria tardía se asoció a ictus lacunar y alcoholismo. Solo el 2,4% recibió trombólisis. Independientemente de la trombólisis, la llegada en < 3 h se asoció a menor mortalidad a los 3 y 6 meses, además de menos complicaciones intrahospitalarias. Conclusiones: Una proporción importante de pacientes tuvo un tiempo de llegada hospitalaria temprana; sin embargo, menos del 3% recibió trombólisis. Aunque muchos factores se asociaron a la llegada temprana, es prioritario identificar las barreras intrahospitalarias que obstaculizan la trombólisis. Abstract: Introduction: Information regarding hospital arrival times after acute ischaemic stroke (AIS) has mainly been gathered from countries with specialised stroke units. Little data from emerging nations is available. We aim to identify factors associated with achieving hospital arrival times of less than 1, 3, and 6 hours, and analyse how arrival times are related to functional outcomes after AIS. Methods: We analysed data from patients with AIS included in the PREMIER study (Primer Registro Mexicano de Isquemia Cerebral) which defined time from symptom onset to hospital arrival. The functional prognosis at 30 days and at 3, 6, and 12 months was evaluated using the modified Rankin Scale. Results: Among 1096 patients with AIS, 61 (6%) arrived in

Background: Isolated posterior fossa parenchymal lesions associated with cerebral venous thrombosis (CVT) are rare. Posterior fossa lesions are an independent predictor of death in CVT. We aim to describe the characteristics and outcome of patients with CVT and isolated posterior fossa lesions and assess the safety of anticoagulation in patients with posterior fossa lesions associated with CVT. Methods: We retrieved data from all patients with posterior fossa parenchymal lesions in the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) cohort related to clinical features, therapy and outcome. Fisher's exact test was used to evaluate associations. To assess the safety of anticoagulation in CVT patients with posterior fossa lesions we considered all patients with a lesion in this topography, either isolated or with concomitant supratentorial lesions, and compared the rate of new intracranial haemorrhages on repeated imaging with the remaining cohort. Results: Out of 624 patients, 12 had isolated posterior fossa lesions and 14 had posterior fossa lesion with accompanying supratentorial lesions. The lateral sinus was most frequently occluded (n = 11). Involvement of the superior sagittal sinus was significantly less frequent compared to the remaining patients of the cohort (p = 0.013). None of the patients with isolated posterior fossa lesion died but 3 remained dependent on follow-up. Poor outcome (modified Rankin Scale ≥3) was more frequent in patients with any posterior fossa lesion, even when on anticoagulation (29.2% vs. 11.9%; OR 3.04; 95% CI 1.2-7.6; p = 0.018). Of the 24 anticoagulated patients with a posterior fossa lesion, 3 (12.5%) had new haemorrhages on repeated imaging, compared with 30 out of 495 anticoagulated patients (6.1%) without posterior fossa lesions (p = 0.19). Conclusions: We describe the largest series of CVT patients with associated posterior fossa lesions. When compared to anticoagulated CVT patients without posterior fossa lesions, CVT patients with posterior fossa lesions on full anticoagulation did not have a significant increase in the rate of new intracranial haemorrhages.

Background and Purpose: The efficacy of cerebrospinal fluid shunting to reduce intracranial hypertension and prevent fatal brain herniation in acute cerebral venous thrombosis (CVT) is unknown. Method: From the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) and a systematic literature review, we retrieved acute CVT patients treated only with shunting (external ventricular drain, ventriculoperitoneal or ventriculojugular shunt). Outcome was classified at 6 months and final follow-up by the modified Rankin Scale (mRS). Results: 15 patients were collected (9 from the ISCVT and 6 from the review) who were treated with a shunt (external ventricular drain in 6 patients, a ventriculoperitoneal shunt in 8 patients or an unspecified type of shunt in another one). Eight patients (53.3%) regained independence (mRS 0-2), while 2 patients (13.3%) were left with a severe handicap (mRS 4-6) and 4 (26.7%) died despite treatment. Five patients with parenchymal lesions were shunted within 48 h from admission deterioration, 4 with an external ventricular drain: 2 (40%) recovered to independence, 2 (40%) had a severe handicap and 1 (20%) died. In contrast, all 3 patients with intracranial hypertension and no parenchymal lesions receiving a ventriculoperitoneal shunt later than 48 h regained independence. Conclusion and Implications: A quarter of acute CVT patients treated with a shunt died, and only half regained independence. With the limitation of the small number of subjects, this review suggests that shunting does not appear to be effective in preventing death from brain herniation in acute CVT. We cannot exclude that shunting may benefit patients with sustained intracranial hypertension and no parenchymal lesions.

Background: Current evidence shows that uric acid is a potent antioxidant whose serum concentration increases rapidly after acute ischemic stroke (AIS). Nevertheless, the re-lationship between serum uric acid (SUA) levels and AIS outcome remains debatable. We aimed to describe the prognostic significance of SUA in AIS. Methods: We studied 463 patients (52% men, mean age 68 years, 13% with glomerular filtration rate Results: Mean SUA concentration at hospital arrival was 6.1 ± 3.7 mg/dl (362.8 ± 220.0 μmol/l). Compared with cases with higher SUA levels at hospital admission, patients with ≤4.5 mg/dl (≤267.7 μmol/l; the lowest tertile of the sample) had more cases of a very good 30-day outcome (30.5 vs. 18.9%, respectively; p = 0.004). SUA was not associated with mortality or functional dependence (mRS >2) at 30 days, or with any outcome measure at 3, 6 or 12 months poststroke. After adjustment for age, gender, stroke type and severity (NIHSS Conclusions: A low SUA concentration is modestly associated with a very good short-term outcome. Our findings support the hypothesis that SUA is more a marker of the magnitude of the cerebral infarction than an independent predictor of stroke outcome.

Objective: To analyse the outcome of cerebral venous thrombosis (CVT) patients presenting with isolated headache, specifically to compare isolated headache patients with early vs. late CVT diagnosis. Method: In the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) database we compared the outcome of patients with isolated headache and a CVT diagnosed early (≤7 days from onset) vs. late (>7 days). We retrieved 100 patients with isolated headache, 52 patients with early CVT diagnosis (early isolated headache) and 48 with late CVT diagnosis (late isolated headache). Results: Neurological worsening was more frequent within early isolated headache patients (23% vs. 8%) (p = 0.045). At the last follow-up (median 411 days), 93% patients had a complete recovery, and 4% were dead or dependent, with no significant difference between early isolated headache and late isolated headache. Conclusion: The outcome of CVT patients with isolated headache diagnosed early or late was similarly favourable, but there was a higher proportion of neurological worsening in the acute phase among early isolated headache patients, who need close neurological monitoring.

Resumen: Antecedentes: En menores de 45 años, el infarto cerebral (IC) criptogénico representa hasta el 40% de los casos. El objetivo de la presente serie es determinar la tasa de recurrencia, la evolución clínica funcional a largo plazo y las características de imagen de pacientes menores de 45 años, con IC criptogénico. Métodos: 98 pacientes con diagnóstico confirmado de IC criptogénico fueron seguidos durante una mediana de 54 meses (rango de 12 a 238). Registramos los datos demográficos, factores de riesgo, hallazgos clínicos, de laboratorio y de imagen, así como las complicaciones y la evolución funcional. La evaluación de los casos incluyó estudios de imagen vascular intra y extracraneal, ecocardiograma y dos determinaciones de estudios protrombóticos. Resultados: Esta serie representa el 11% de los casos de IC en jóvenes en nuestro hospital. La edad promedio de los casos fue de 39,5 ± 5, 48 (49%) fueron mujeres, 6 (6%) tenían hipertensión arterial, 11 (11%) hipercolesterolemia, 7 (7%) antecedente de migraña, 32 (33%) de tabaquismo activo y 11 (11%) de alcoholismo. Todos los casos fueron manejados con aspirina. Se observó buen pronóstico funcional (Rankin 0 a 2) en 65 (66%) casos y recurrencia en 4 (4%). La circulación anterior (parcial en 56%, total 12%) fue la más afectada y en 87 (88%) casos el infarto fue único. Conclusiones: En esta serie, los IC criptogénicos fueron mayoritariamente únicos, con baja recurrencia y buen pronóstico funcional a largo plazo. Los infartos totales de circulación anterior se correlacionaron con mal pronóstico. Abstract: Background: Around 40% of strokes in young people are labelled as infarcts of undetermined cause. The aim of this study was to determine the image characteristics, the long-term functional outcome and recurrence after cryptogenic ischaemic stroke. Methods: We studied ninety-eight patients under 45 years of age during a median follow up of 54 months (range 12-238), with ischaemic stroke of undetermined cause. We registered vascular risk factors, clinical syndrome, laboratory and imaging results. We used Rankin disability score to assess functional outcome. The cases were evaluated with intracranial and extracranial vascular imaging studies, echocardiogram, and at least two determinations of prothrombotic states. Results: In our hospital 11% of the patients with cerebral infarction under 45 years of age were labelled as cryptogenic. The mean age of the cases was 39.5 ± 5, 48 (49%) were women, 6 (6%) had arterial hypertension, 7 (7%) prior history of migraine, 32 (33%) were active smokers, 11 (11%) had hypercholesterolemia, and 11 (11%) had alcoholism. All cases were treated with aspirin. We observed good functional outcome (Rankin 0-2) in 65 (65%) cases. The anterior circulation was the most affected (partial in 56%, total in 12%). Infarction was unique in 87 (88%) cases. Recurrence was observed in 4 (4%) cases. Conclusions: In this study cryptogenic cerebral infarctions were mostly single, had low recurrence and good functional outcome in the long-term follow-up. Total anterior circulation infarctions correlated with poor outcome. Palabras clave: Infarto cerebral en joven, Pronóstico, Recurrencia, Keywords: Cryptogenic infarct, Recurrence, Outcome

Background and Purpose— Herniation attributable to unilateral mass effect is the major cause of death in cerebral venous thrombosis (CVT). Decompressive surgery may be lifesaving in these patients. Methods— Retrospective registry of cases of acute CVT treated with decompressive surgery (craniectomy or hematoma evacuation) in 22 centers and systematic review of all published cases of CVT treated with decompressive surgery. The primary outcome was the score on the modified Rankin Scale (mRS) score at last follow-up, dichotomized between favorable (mRS score, 0–4) and unfavorable outcome (mRS score, 5 or death). Secondary outcomes were complete recovery (mRS score 0–1), independence (mRS score, 0–2), severe dependence (mRS score, 4–5), and death at last available follow-up. Results— Sixty-nine patients were included and 38 were from the registry. Decompressive craniectomy was performed in 45 patients, hematoma evacuation was performed in 7, and both interventions were performed in 17 patients. At last follow-up (median, 12 months) only 12 (17.4%) had un unfavorable outcome. Twenty-six (37.7%) had mRS score 0 to 1, 39 (56.5%) had mRS score 0 to 2, 4 (5.8%) were alive with mRS score 4 to 5, and 11 (15.9%) patients died. Three of the 9 patients with bilateral fixed pupils recovered completely. Comatose patients were less likely to be independent (mRS score 0–2) than noncomatose patients (45% versus 84%; P =0.003). Patients with bilateral lesions were more likely to have unfavorable outcomes (50% versus 11%; P =0.004) and to die (42% versus 11%; P =0.025). Conclusions— In CVT patients with large parenchymal lesions causing herniation, decompressive surgery was lifesaving and often resulted in good functional outcome, even in patients with severe clinical conditions.

Background: Around 40% of strokes in young people are labelled as infarcts of undetermined cause. The aim of this study was to determine the image characteristics, the long-term functional outcome and recurrence after cryptogenic ischaemic stroke. Methods: We studied ninety-eight patients under 45 years of age during a median follow up of 54 months (range 12–238), with ischaemic stroke of undetermined cause. We registered vascular risk factors, clinical syndrome, laboratory and imaging results. We used Rankin disability score to assess functional outcome. The cases were evaluated with intracranial and extracranial vascular imaging studies, echocardiogram, and at least two determinations of prothrombotic states. Results: In our hospital 11% of the patients with cerebral infarction under 45 years of age were labelled as cryptogenic. The mean age of the cases was 39.5±5, 48 (49%) were women, 6 (6%) had arterial hypertension, 7 (7%) prior history of migraine, 32 (33%) were active smokers, 11 (11%) had hypercholesterolemia, and 11 (11%) had alcoholism. All cases were treated with aspirin. We observed good functional outcome (Rankin 0–2) in 65 (65%) cases. The anterior circulation was the most affected (partial in 56%, total in 12%). Infarction was unique in 87 (88%) cases. Recurrence was observed in 4 (4%) cases. Conclusions: In this study cryptogenic cerebral infarctions were mostly single, had low recurrence and good functional outcome in the long-term follow-up. Total anterior circulation infarctions correlated with poor outcome. Resumen: Antecedentes: En menores de 45 años, el infarto cerebral (IC) criptogénico representa hasta el 40% de los casos. El objetivo de la presente serie es determinar la tasa de recurrencia, la evolución clínica funcional a largo plazo y las características de imagen de pacientes menores de 45 años, con IC criptogénico. Métodos: 98 pacientes con diagnóstico confirmado de IC criptogénico fueron seguidos durante una mediana de 54 meses (rango de 12 a 238). Registramos los datos demográficos, factores de riesgo, hallazgos clínicos, de laboratorio y de imagen, así como las complicaciones y la evolución funcional. La evaluación de los casos incluyó estudios de imagen vascular intra y extracraneal, ecocardiograma y dos determinaciones de estudios protrombóticos. Resultados: Esta serie representa el 11% de los casos de IC en jóvenes en nuestro hospital. La edad promedio de los casos fue de 39,5±5, 48 (49%) fueron mujeres, 6 (6%) tenían hipertensión arterial, 11 (11%) hipercolesterolemia, 7 (7%) antecedente de migraña, 32 (33%) de tabaquismo activo y 11 (11%) de alcoholismo. Todos los casos fueron manejados con aspirina. Se observó buen pronóstico funcional (Rankin 0 a 2) en 65 (66%) casos y recurrencia en 4 (4%). La circulación anterior (parcial en 56%, total 12%) fue la más afectada y en 87 (88%) casos el infarto fue único. Conclusiones: En esta serie, los IC criptogénicos fueron mayoritariamente únicos, con baja recurrencia y buen pronóstico funcional a largo plazo. Los infartos totales de circulación anterior se correlacionaron con mal pronóstico. Keywords: Cryptogenic infarct, Recurrence, Outcome, Palabras clave: Infarto cerebral en joven, Pronóstico, Recurrencia

Background and purpose: Although pregnancy and postpartum have long been associated with stroke, there is a dearth of information in Latino-American populations. The aim of this study was to describe the cerebrovascular complications occurring during pregnancy/postpartum and compare the characteristics amongst stroke types occurring in this period in Hispanic women. Patients and methods: We studied 240 women with cerebrovascular complications during pregnancy and the first 5 weeks postpartum, from our stroke registry. Patients were classified into three groups: cerebral venous thrombosis (CVT), ischaemic stroke (IS), and intracerebral hemorrhage (ICH). For each group, clinical data, timing of the event, and outcome were analyzed. Results: Of the 240 women, 136 had CVT (56.7%), 64 IS (26.7%), and 40 ICH (16.6%). In 72 women (30%), the event occurred during pregnancy, in 153 (64%) during postpartum, and in 15 (6%) closely related to labor. CVT was more common in the first trimester of pregnancy and in the second and third weeks following delivery; whilst IS and ICH were seen mainly during pregnancy and the first 2 weeks following delivery. Pre-eclampsia/eclampsia was more common in patients with ICH (57.5%) and IS (36%) than in those with CVT (9.6%) (P

Background and Purpose— There is no consensus whether to use unfractionated heparin or low–molecular weight heparin for the treatment of cerebral venous thrombosis. We examined the effect on clinical outcome of each type of heparin. Methods— A nonrandomized comparison of a prospective cohort study (the International Study on Cerebral Vein and Dural Sinus Thrombosis) of 624 patients with cerebral venous thrombosis. Patients not treated with heparin (n=107) and those who sequentially received both types of heparin (n=99) were excluded from the primary analysis. The latter were included in a secondary analysis, allocated according to the type of heparin given first. The primary end point was functional independency at 6 months (modified Rankin scale score ≤2). Secondary end points were complete recovery (modified Rankin scale score 0 to 1), mortality, and new intracranial hemorrhages. Results— A total of 119 patients received low–molecular weight heparin (28%) and 302 received unfractionated heparin (72%). Significantly more patients treated with low–molecular weight heparin were functionally independent after 6 months, both in univariate analysis (odds ratio, 2.1; CI, 1.0 to 4.2) and after adjustment for prognostic factors and imbalances (odds ratio, 2.4; CI, 1.0 to 5.7). In the secondary analysis, there was a similar, nonsignificant trend (odds ratio, 1.7; CI, 0.80 to 3.6). Low–molecular weight heparin was associated with less new intracerebral hemorrhages (adjusted odds ratio, 0.29; CI, 0.07 to 1.3), especially in patients with intracerebral lesions at baseline (adjusted odds ratio, 0.19; CI, 0.04 to 0.99). There was no difference in complete recovery and mortality. Conclusions— This nonrandomized study in patients with cerebral venous thrombosis suggests a better efficacy and safety of low–molecular weight heparin over unfractionated heparin. Low–molecular weight heparin seems preferable above unfractionated heparin for the initial treatment of cerebral venous thrombosis.

Background and Purpose— Cerebellar venous infarction or hemorrhage due to isolated venous thrombosis of the posterior fossa is a rare form of intracranial vein thrombosis that can be unsuspected in clinical practice. Methods— We studied 230 patients with intracranial vein thrombosis, identifying 9 (3.9%: 7 women, mean age 34 years) with neuroimaging or histopathologic evidence of localized posterior fossa vein thrombosis causing parenchymal injury limited exclusively to the cerebellum. Results— All patients had an insidious presentation suggesting other diagnoses. Intracranial hypertension (n=6) and cerebellar (n=4) syndromes were the main clinical presentations. Intracranial vein thrombosis was idiopathic in 3 patients; associated with puerperium in 3; and with contraceptives, protein C deficiency, and dehydration in 1 case each. CT was abnormal but not diagnostic in 5 patients, showing a cerebellar hypodensity with fourth ventricle compression and variable hydrocephalus in 5 patients, and cerebellar hemorrhage in 2. Conventional MRI provided diagnosis in 6 cases, showing the causal thrombosis and cerebellar involvement; angiography was practiced in 2 of them, confirming the findings identified by MRI. In the other 3 patients, diagnosis was reached by histopathology. Thromboses were localized at the straight sinus (n=4), lateral sinuses (n=3), and superior petrosal vein (n=2). The acute case fatality rate was 22.2% (n=2), 1 (11.1%) patient was discharged in a vegetative state, 1 (11.1%) was severely disabled, and 5 (55.6%) were moderately disabled. Conclusions— Isolated venous thrombosis of the posterior fossa is infrequent and implies a challenging diagnosis. Risk factors for intracranial vein thrombosis and atypical cerebellar findings on CT should lead to further MRI assessment.

Background and Purpose: Brain imaging of patients with acute cerebral venous thrombosis often shows parenchymal hemorrhagic and nonhemorrhagic lesions. The clinical relevance of nonhemorrhagic lesions is poorly known. Method: In the International Study on Cerebral Vein and Dural Sinus Thrombosis cohort, demographic, clinical, risk factor, prognosis and imaging findings were compared between patients with parenchymal nonhemorrhagic lesions and no hemorrhagic lesions (NHL) and (1) patients with parenchymal hemorrhagic lesions (HL) and (2) patients without brain lesions. Predictors of prognosis at the end of follow-up in the NHL group were analyzed by bivariate and Cox regression methods. Results: We identified 147 patients (23.6%) with NHL. When compared to patients without brain lesions (n = 309), those with NHL more often presented mental status disturbances, aphasia, decreased alertness, motor deficits, seizures, occlusions of the straight sinus, deep venous system and cortical veins. Patients with NHL had a better prognosis in the acute phase and at the end of follow-up than those with HL, but a worse one than patients without brain lesions, as more NHL patients were dead or dependent (modified Rankin Scale score = 3–6) at discharge (19.7 vs. 6.5%, p < 0.001) and final follow-up (14.3 vs. 7.4%, p = 0.03). In Cox regression analysis, coma (HR = 13.7; 95% CI = 4.3–43.7) and thrombosis of the deep venous system (HR = 3.5; 95% CI = 1.4–8.7) were associated with death or dependency at the end of follow-up. Conclusion: Cerebral venous thrombosis patients with NHL are intermediate between patients without brain lesions and those with HL, both in initial clinical picture and prognosis.

Background and Purpose— Although intracerebral hemorrhages are frequent in patients with cerebral venous thrombosis, and lead to worse outcome, predictors of outcome in cerebral venous thrombosis patients with intracerebral hemorrhages have never been evaluated in adequately powered studies. Methods— This study was conducted as a part of the International Study on Cerebral Vein and Dural Sinus Thrombosis. We evaluated predictors of outcome in cerebral venous thrombosis patients who had an “early intracerebral hemorrhage,” ie, intracerebral hemorrhages already present at time of diagnosis of cerebral venous thrombosis by a logistic regression analysis, with a modified Rankin scale 3 to 6 at month 6 as dependent variable. The same analysis was performed with “delayed intracerebral hemorrhages,” ie, intracerebral hemorrhages that occurred after the diagnosis of cerebral venous thrombosis, as dependent variable. Results— Of 624 patients recruited in International Study on Cerebral Vein and Dural Sinus Thrombosis, 245 (39%) had an early intracerebral hemorrhage: at month 6, 51 (21%) of them had a modified Rankin Scale 3 to 6. Independent predictors of having modified Rankin scale 3 to 6 at month 6 were older age (adjusted odds ratio for 1-year increase in age, 1.05; 95% CI, 1.02 to 1.08); male gender (adjusted odds ratio, 3.25; 95% CI, 1.29 to 8.16); having a deep cerebral venous system thrombosis (adjusted odds ratio, 5.43; 95% CI, 1.67 to 17.61) or a right lateral sinus thrombosis (adjusted odds ratio, 2.56; 95% CI, 1.03 to 6.40); and having a motor deficit (adjusted odds ratio, 2.94; 95% CI, 1.21 to 7.10). Of the 36 patients who had a delayed intracerebral hemorrhage, those who had a modified Rankin scale 3 to 6 at month 6 were less likely to have received heparin at the acute stage, and more likely to have had early intracerebral hemorrhage. Conclusion— Among patients with early intracerebral hemorrhage, those who were older, men, had a thrombosis of the deep cerebral venous system or of the right lateral sinus, and a motor deficit were at higher risk for death or dependency at month 6. This subgroup of patients with predictors of poor outcome can be the target for new therapeutic strategies.

Seventy-eight patients with aseptic cerebral venous thrombosis between 1966 and 1990 were reviewed in order to determine prognostic factors for this condition. Sixty-eight patients were women. The average age of the patients was 30.5 years. Fifty-two percent of patients developed the thrombosis during the postpartum or puerperal stage. The clinical manifestations that were associated with a poor prognosis were: stupor or coma, bilateral pyramidal tract signs, generalized seizures, meningeal signs, bilateral lesions on computed tomography, and hemorrhagic cerebrospinal fluid. Using these clinical features, a prognostic scale is proposed with a positive predictive value of 0.98 for a good prognosis and 0.96 for a poor prognosis.

Thirty-five young patients with ischemic stroke were studied via color-flow echocardiography in order to detect patent foramen ovale. The stroke patients were divided into two groups: those with undetermined stroke etiology (Group I) and those with determined stroke etiology (Group II). The prevalence of patent foramen ovale was 67% in Group I and 43% in Group II. Our results suggest that patent foramen ovale is more frequent in stroke patients, especially in patients without defined etiology. We also suggest that paradoxical embolism is more frequent than previously thought.

Background and Purpose: We describe the natural history, functional prognosis and long-term recurrences of patients with dissection of cervical arteries (DCA) in a sequential observational study. Methods: We describe 130 patients with angiographically-proven DCA admitted to the Neurology Institute in Mexico City (Mexico), and analyzed clinical and neuroimaging data, treatment and outcome. Treatment with either anticoagulation or aspirin was decided by the primary physician. Primary outcome measures were recurrence (stroke and death) and clinical outcome at 6 months. Follow-up studies were performed to determine recanalization. Results: Mean age was 35.4 years; 4 patients died (3%) and 126 were followed for 3,906 person/years; 17 patients (13%) had a heralding ischemic cerebral event (6 strokes, 11 TIAS) about 8 days before the diagnosis of DCA. After diagnosis, recurrent ischemic stroke occurred in 6 patients (4.8%) within the 2 first weeks (1.5 persons/1,000 follow-up years). No significant differences were found between aspirin and anticoagulation. Recanalization was more frequent in vertebral dissections. Complete recanalization of vertebral dissections was associated with a favorable prognosis [OR 3.2 (95% CI 1.1–8.8; p = 0.02)]. Conclusions: In Mexico, DCA affects young adults and may present with a heralding stroke or TIA. We found rare, early ischemic recurrences. Vertebral territory dissections had better prognosis than carotid ones, particularly in patients with demonstrated complete recanalization.

Intracerebral hemorrhage (ICH) accounts for approximately 10% of strokes. Its causes include hypertension and cerebral amyloid angiopathy in the middle-aged and elderly, respectively, while vascular malformations predominate in the younger than 45 years old population. Recurrence of ICH is not as low as it was traditionally thought, and overall it is about 4.5% for an aggregate of several studies with different lengths of follow-up. Most of these recurrences occur over a 1-2 year period after the initial episode of ICH, but late recurrence (over several years) is not uncommon, leading to cumulative frequencies of recurrence of up to 25-55% after 7-8 years of follow-up in some series. The main risk factors for recurrence are age, poorly controlled hypertension, lobar location (probably due to cerebral amyloid angiopathy), presence of asymptomatic microhemorrhages, and carrying the ϵ2 and ϵ4 alleles of the apolipoprotein E gene. The initial location of ICH (ganglionic vs. lobar) is generally predictive of the same topography for the recurrent event. Recurrent ICH is associated with high mortality, in the order of 70%.

Background and Purpose— The causes of death of patients with cerebral venous thrombosis (CVT) have not been systematically addressed in previous studies. We aimed to analyze the causes and predictors of death during the acute phase of CVT in the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) to identify preventable or treatable causes. Methods— ISCVT is a multinational, prospective, observational study including 624 patients with CVT occurring between May 1998 and May 2001, in which 27 patients (4.3%) died during the acute phase, 21 (3.4%) within 30 days from symptom onset. Inclusion forms and a questionnaire assessing the causes of death were analyzed. A logistic regression analysis was performed to identify the predictors of death within 30 days from symptom onset of CVT. Results— Median time between onset of symptoms and death was 13 days and between diagnosis and death, 5 days. Causes of death were mainly transtentorial herniation due to a unilateral focal mass effect (10 patients) or to diffuse edema and multiple parenchymal lesions (10 patients). Independent predictors of death were coma (odds ratio [OR], 8.8; 95% confidence interval [CI], 2.8 to 27.7), mental disturbance (OR, 2.5; 95% CI 0.9 to 7.3), deep CVT thrombosis (OR, 8.5; 95% CI, 2.6 to 27.8), right intracerebral hemorrhage (OR, 3.4; 95% CI, 1.1 to 10.6), and posterior fossa lesion (OR, 6.5; 95% CI, 1.3 to 31.7). Worsening of previous focal or de novo focal deficits increased the risk of death. Conclusions— The main causes of acute death were neurologic, the most frequent mechanism being transtentorial herniation.

Prediction of intracerebral hemorrhage (ICH) in patients with cavernous angiomas is not totally elucidated. The aims of our study were to determine the rate of cerebral hemorrhage, its associated factors, and the clinical outcome in patients with cavernous angiomas in a Hispanic population.We studied 133 patients with cavernous angiomas. The patients were classified into two groups depending on whether they presented an ICH. A comparative analysis of demographics and clinical data, neuroimaging characteristics, and prognosis was carried out in patients with and without hemorrhage. The hemorrhage rate (expressed as the percentage per patient per year) was also estimated.Seventy-eight patients (59%) had hemorrhage. Non-lobar location of angiomas was associated with hemorrhage [OR 4.82 (CI 95% 2.17-10.73; p=0.001)]. In contrast, factors associated with a decreased risk of hemorrhage were a family history of epilepsy [OR 0.30 (CI 95% 0.10-0.79; p=0.016)] and lobar location of the angiomas [OR 0.21 (CI 95% 0.09-0.46; p=0.001)]. The hemorrhagic rate of 1.71% per patient per year was influenced by the location. It was only 1.22% per patient per year in lobar angiomas and 2.33, 2.39, and 2.82% per patient per year for brainstem, cerebellum, and deep hemispheric angiomas, respectively.The non-lobar location of cavernous angiomas gives a higher risk of hemorrhage in our Mexican mestizo population, without the hemorrhage being related to either age or sex.

Background and Purpose— Elevated plasma levels of homocysteine are associated with an increased risk of deep-vein thrombosis. Through a case–control study, we examined the potential association among homocysteine, folate and vitamin B 12 levels, and the common C677→T mutation in the methylene tetrahydrofolate reductase ( MTHFR ) gene in patients with cerebral venous thrombosis (CVT). Methods— Forty-five patients with CVT and 90 control subjects were studied. Plasma levels of homocysteine (fasting and after methionine load), folate, and vitamin B 12 were measured. Genotyping of the MTHFR gene was also performed. The estimated risk of CVT associated with hyperhomocysteinemia, low vitamin levels, and MTHFR mutation were expressed as odds ratio (OR) and its 95% CI (crude and after adjusting by other independent variables). Results— The adjusted OR for CVT associated with high (>90th percentile) fasting levels of homocysteine was 4.6 (1.6 to 12.8). The association between low plasma folate values (MTHFR mutation in patients with CVT (22% versus 10%), but it was not statistically significant ( P =0.098). Patients with MTHFR mutation and low folate levels presented the highest homocysteine levels. Conclusions— High plasma concentrations of homocysteine and low plasma folate levels were associated with an increased risk of CVT in this population in which low socioeconomic conditions and deficient nutritional status may contribute to its relatively high incidence.

Background and Purpose— We investigated whether lacunar infarct (LI) patients with >1 lacune have different vascular risk factors, a different prognosis, and poorer functional outcome than those with a single lacune. Methods— The study included 175 first-ever LI patients. The group was divided according to the presence of multiple (n=136) or single (n=39) LI. The association of single or multiple LI with the principal vascular risk factors, leukoaraiosis, outcome, and recurrence was investigated with logistic regression models that included age, sex, and cardiac disease. Results— No significant differences were found between single and multiple LI with respect to age, hypertension, hyperlipidemia, smoking, and heavy alcohol drinking. Diabetes mellitus (odds ratio [OR], 2.43; 95% CI, 1.09 to 5.4), high levels of hematocrit (>0.47) (OR, 1.09; 95% CI, 1.04 to 1.21), and leukoaraiosis (OR, 3.58; 95% CI, 1.77 to 7.51) were significantly related to multiple but not to single LI. Stroke recurrence rate was 7.7% in patients with single LI and 24.3% in the multiple LI group (OR, 3.84; 95% CI, 1.1 to 13.3). During a median follow-up of 12 months (range, 6 to 156 months), 94% of the single LI patients and 77.2% of the multiple LI patients had favorable outcomes (Rankin Scale score 0 to 2) (OR, 5.4; 95% CI, 1.25 to 23.9). Conclusions— Diabetes mellitus, leukoaraiosis, and high levels of hematocrit are important risk factors in patients with >1 LI. The presence of multiple LI may be an important prognostic indicator not only for functional recovery but also for a higher rate of recurrence.

Background and Purpose— Although headache is the most common symptom in cerebral venous thrombosis, 5% to 30% of patients do not report headache at baseline. Characteristics of these patients have not been investigated. Methods— In post hoc analysis of the International Study on Cerebral Vein and Dural Sinus Thrombosis study, patients who might not have been able to report headache (aphasia, stupor, coma, or mental status disorder) were excluded. Results— Three hundred eighty-two of the original 624 patients (61%) were included, of whom 38 (10%) did not report headache at baseline. Patients without headache were older (mean age, 45 versus 37; P =0.001) and less often female (63% versus 77%; P =0.06). Paresis (42% versus 27%; P =0.05) and seizures (58% versus 32%; P =0.001) were more common in patients without headache, whereas papilledema was less common (8% versus 35%; P =0.001). Isolated cortical vein thrombosis (16% versus 2%; P =0.001), brain parenchymal lesions (66% versus 46%; P =0.02), and malignancies (18% versus 6%; P =0.009) were more common among patients without headache. Outcome at last follow-up was worse in patients without headache (modified Rankin Scale, 0–1; 76% versus 89%; P =0.04; mortality, 13% versus 5%; P =0.05), but after adjustment for prognostic variables, headache was not an independent predictor of outcome. Conclusions— Patients with cerebral venous thrombosis but without headache are a heterogeneous subgroup, in which older patients, men, and some associated conditions are over-represented. Patients without headache had a worse clinical outcome, but after adjustment for imbalances, headache was not an independent predictor of outcome.

Background and Purpose —The frequency of intracerebral hemorrhages (ICHs) in people aged ≤40 years has been poorly studied. We investigated the incidence, causes, locations, and prognosis of ICH in young patients. Methods —We evaluated all consecutive patients with neuroimaging evidence or pathological confirmation of symptomatic ICH. We excluded patients with primary subarachnoid or traumatic hemorrhage, past evidence of vascular malformation, or brain tumor. We analyzed the risk factors, number, locations, and causes of ICH, and final outcome measured by the modified Glasgow Outcome Scale. Results —We retrospectively evaluated 200 patients (mean age, 27 years; range, 15 to 40 years). The most frequent risk factors were tobacco use (20%), hypocholesterolemia (35%), hypertension, (13%), and alcohol use (10%). The locations of ICH were lobar (55%), basal ganglia/internal capsule (22%), and others (24%). The most common causes of ICH were vascular malformations (49%), including cavernous angioma, and hypertension (11%). Cryptogenic ICH was considered in 15%. Other causes included cerebral venous thrombosis (5%) and sympathomimetic drug use (4%). The majority of patients with ICH that resulted from hypertension were aged >31 years (odds ratio, 3.48), and those with ICH that resulted from arteriovenous malformations were aged Conclusions —ICHs in young people are mainly lobar in location and result from vascular malformation. Hypertension causes most cases in which the ICH is located in the basal ganglia. Mortality and morbidity in the acute phase are low and are related to hypertension as the cause of ICH.

OBJETIVO: Evaluar la frecuencia y los factores determinantes de aterosclerosis carotidea en una comunidad de la ciudad de Mexico. MATERIAL Y METODOS: Se realizo, de julio de 1993 a enero de 1996, una ultrasonografia carotidea en 145 participantes del proyecto CUPA, que consiste en un estudio de vigilancia epidemiologica. Se investigo la presencia de aterosclerosis carotidea y su relacion con factores de riesgo cardiovascular. RESULTADOS: La prevalencia de aterosclerosis carotidea detectada por ultrasonografia fue de 64.8%. En 64 personas (44.1%) se documento engrosamiento del complejo intima-media de la pared aterial y en 82 sujetos (56.5%) se observaron placas de ateroma (concomitantes con engrosamiento intima-media en 52 individuos). En solo ocho personas (5.5%) las placas de ateroma se asociaron a estenosis hemidamicamente significativa. No se encontraron diferencias en la prevalencia de aterosclerosis en relacion con el sexo (hombres, 61.9% y mujeres, 66.0%). Los factores de riesgo asociados con aterosclerosis fueron: edad (p

Background and Purpose —The frequency of recurrent primary cerebral hemorrhage (RPCH), mainly in cases related to hypertension, has been considered low. This study investigated the frequency, mechanisms, and prognosis of RPCH. Methods —We evaluated 359 patients with neuroimaging evidence of cerebral hemorrhage and selected 22 with RPCH. Results —Five patients (23%) were older than 70 years at the first cerebral hemorrhage. Mean ages at the first and second hemorrhages were 60 and 63 years, respectively. Risk factors included hypertension (86%), diabetes (27%), and tobacco and alcohol use (each 14%). Hypocholesterolemia was demonstrated in 35% of the patients. The most common pattern of recurrent bleeding was ganglionic-ganglionic, mainly related to hypertension. Overall mortality was 32%. Forty-one percent and 27% of patients, respectively, had incapacitating and nonincapacitating sequelae; 2 of the latter had RPCH with a lobar location. Ganglionic-ganglionic hemorrhage was associated with a poor prognosis; otherwise, this pattern was uncommon in patients with nonincapacitating sequelae. Analysis of the control of risk factors, primarily hypertension after the first cerebral hemorrhage, disclosed that 56% of patients did not gain subsequent control. Conclusions —Rebleeding after a first primary intracerebral hemorrhage is not uncommon. The main topographic pattern of bleeding, ganglionic-ganglionic, is likely the result of hypertension; the less common lobar-lobar pattern probably results from amyloid angiopathy.

Although a considerable body of scientific data is now available on neuroprotection in acute ischaemic stroke, this field is not yet established in clinical practice. At its third meeting, the European Ad Hoc Consensus Group considered the potential for neuroprotection in acute stroke and the practical problems attendant on the existence of a very limited therapeutic window before irreversible brain damage occurs, and came to the following conclusions. Neuroprotectants in Clinical Development: Convincing clinical evidence for an efficacious neuroprotective treatment in acute stroke is still required. Caution should be exercised in interpreting and extrapolating experimental results to stroke patients, who are a very heterogeneous group. The limitations of the time windows and the outcome measures chosen in trials of acute stroke therapy have an important influence on the results. The overall distribution of functional outcomes provides more statistical information than the proportion above a threshold outcome value. Neurological outcome should also be assessed. Neuroprotectants should not be tested clinically in phase II or phase III trials in a time window that exceeds those determined in experimental studies. The harmful effects of a drug in humans may override its neuroprotective potential determined in animals. Agents that act at several different levels in the ischaemic cascade may be more effective than those with a single mechanism of action. Current In-Hospital Management of Acute Stroke: The four major physiological variables that must be monitored and managed are blood pressure, arterial blood gas levels, body temperature, and glycaemia. The effects of controlling these physiological variables have not been studied in prospective trials, though they may all contribute to the outcome of acute ischaemic stroke and affect the duration of the therapeutic window. Optimal physiological parameters are inherently neuroprotective. Trials of new agents for the treatment of acute stroke should aim to maintain these physiological variables as close to normal as possible, and certainly within strictly defined limits. The Place of Neuroprotectants in Acute Stroke Management: Stroke patients are a very heterogeneous group with respect to stroke mechanisms and severity, general condition, age and co-morbidities. At the present time, the only firm guideline than can be proposed for patient selection is the need for early admission to enable neuroprotectant and/or thrombolytic treatment to be started as soon as possible within the therapeutic window. The severity of potential side-effects will largely determine who should assess a patient with suspected stroke and initiate treatment. There is little information on which to base the duration of neuroprotectant therapy, and more experimental data are needed. Even if prehospital treatment proves to be feasible, it should not replace comprehensive stroke management in a specialist hospital unit. Clinical trials of neuroprotectants should only be performed in stroke units. The combined approach of restoring blood flow and providing neuroprotection may be the most productive in human stroke, but current clinical trial design will have to change in order to test combination therapy. Important side-effects are those that interfere with any possible benefit or increase mortality. Pharmaco-Economic Aspects of Neuroprotectants: The early increase in hospital costs associated with neuroprotectant therapy may be balanced by the shorter length of hospital stay and lesser degree of disability of the surviving patients. The overall direct financial cost is highly dependent on the number of patients eligible for neuroprotectant therapy, which is itself dependent on the length of the therapeutic window and the severity of potential side-effects. A treatment that achieves a good functional outcome is the most cost-effective approach.