Patrícia Canhão

Prognosis of Cerebral Vein and Dural Sinus Thrombosis Results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT)

Background and Purpose— The natural history and long-term prognosis of cerebral vein and dural sinus thrombosis (CVT) have not been examined previously by adequately powered prospective studies. Methods— We performed a multinational (21 countries), multicenter (89 centers), prospective observational study. Patients were followed up at 6 months and yearly thereafter. Primary outcome was death or dependence as assessed by modified Rankin Scale (mRS) score >2 at the end of follow-up. Results— From May 1998 to May 2001, 624 adult patients with CVT were registered. At the end of follow-up (median 16 months), 356 patients (57.1%) had no symptom or signs (mRS=0), 137 (22%) had minor residual symptoms (mRS=1), and 47 (7.5%) had mild impairments (mRS=2). Eighteen (2.9%) were moderately impaired (mRS=3), 14 (2.2%) were severely handicapped (mRS=4 or 5), and 52 (8.3%) had died. Multivariate predictors of death or dependence were age >37 years (hazard ratio [HR]=2.0), male sex (HR=1.6), coma (HR=2.7), mental status disorder (HR=2.0), hemorrhage on admission CT scan (HR=1.9), thrombosis of the deep cerebral venous system (HR=2.9), central nervous system infection (HR=3.3), and cancer (HR=2.9). Fourteen patients (2.2%) had a recurrent sinus thrombosis, 27 (4.3%) had other thrombotic events, and 66 (10.6%) had seizures. Conclusions— The prognosis of CVT is better than reported previously. A subgroup (13%) of clinically identifiable CVT patients is at increased risk of bad outcome. These high-risk patients may benefit from more aggressive therapeutic interventions, to be studied in randomized clinical trials.

Effect of a Novel Free Radical Scavenger, Edaravone (MCI-186), on Acute Brain Infarction

Edaravone, a novel free radical scavenger, demonstrates neuroprotective effects by inhibiting vascular endothelial cell injury and ameliorating neuronal damage in ischemic brain models. The present study was undertaken to verify its therapeutic efficacy following acute ischemic stroke. We performed a multicenter, randomized, placebo-controlled, double-blind study on acute ischemic stroke patients commencing within 72 h of onset. Edaravone was infused at a dose of 30 mg, twice a day, for 14 days. At discharge within 3 months or at 3 months after onset, the functional outcome was evaluated using the modified Rankin Scale. Two hundred and fifty-two patients were initially enrolled. Of these, 125 were allocated to the edaravone group and 125 to the placebo group for analysis. Two patients were excluded because of subarachnoid hemorrhage and disseminated intravascular coagulation. A significant improvement in functional outcome was observed in the edaravone group as evaluated by the modified Rankin Scale (p = 0.0382). Edaravone represents a neuroprotective agent which is potentially useful for treating acute ischemic stroke, since it can exert significant effects on functional outcome as compared with placebo.

Causes and Predictors of Death in Cerebral Venous Thrombosis

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.

Thrombolytics for Cerebral Sinus Thrombosis

Background and Purpose: The use of thrombolytics is frequently mentioned in patients with cerebral venous or dural sinus thrombosis (CVDST) who deteriorate despite anticoagulant therapy. The aim of this review was to collect all the published information about their use in CVDST and to assess their efficacy and safety. Methods: To find cases of CVDST treated with thrombolytics, we performed a MEDLINE search from 1966 to July 2001, checked all reference lists of studies found and hand searched volumes of 11 journals. Data was extracted by means of a standardised data extraction form. Proportions and 95% confidence intervals (CI) were calculated for outcomes and complications of thrombolytics. Cases were stratified according to variables that may influence the outcome and subgroups were compared by odds ratios and 95% CI. Results: No randomised clinical trial (RCT) was found. Seventy-two studies (169 patients) were included. Urokinase was the thrombolytic most frequently administered (76%). In the majority of cases the thrombolytic was locally infused in the occluded sinus (88%). At discharge, 10 cases (7%; 95% CI 3–12%) were dependent and 9 cases (5%; 95% CI 2–9%) died. Intracranial haemorrhages occurred in 17% of cases. In 5% they were associated with clinical deterioration. Extracranial haemorrhages occurred in 21%, but only 2% required blood transfusion. Conclusions: Thrombolytics appeared to be reasonably safe in CVDST, but its efficacy cannot be assessed from the published data. Considering that CVDST is an uncommon disease, a randomised controlled trial to assess effectiveness and safety of local thrombolytics in cases of CVDST with poor prognosis is difficult but not impossible to undertake, on a multicentre international collaboration trial.

Cerebral Venous and Sinus Thrombosis in Women

Background and Purpose— Little is known about the gender-specific manifestations of cerebral venous and sinus thrombosis, a disease that is much more common in women than men. Methods— We used data of the International Study on Cerebral Vein and Dural sinus Thrombosis (ISCVT), a multicenter prospective observational study, to analyze gender-specific differences in clinical presentation, etiology, and outcome of cerebral venous thrombosis. Results— Four hundred sixty-five of a total of 624 patients were women (75%). Women were significantly younger, had less often a chronic onset of symptoms, and had more often headache at presentation. There were no gender differences in ancillary investigations or treatment. A gender-specific risk factor (oral contraceptives, pregnancy, puerperium, and hormonal replacement therapy) was present in 65% of women. Women had a better prognosis than men (complete recovery 81% versus 71%l P=0.01), which was entirely due to a better outcome in female patients with gender-specific risk factors. Women without gender-specific risk factors are similar to men in clinical presentation, risk factor profile, and outcome. Logistic regression analysis confirmed that the absence of gender-specific risk factors is a strong and independent predictor of poor outcome in women with sinus thrombosis (OR, 3.7; CI, 1.9 to 7.4). Conclusions— Our study identified important differences between women and men in presentation, course, and risk factors of cerebral venous and sinus thrombosis and showed that women with a gender-specific risk factor have a much better prognosis than other patients.

Decompressive Surgery in Cerebrovenous Thrombosis A Multicenter Registry and a Systematic Review of Individual Patient Data

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.

Predictors of Outcome in Patients With Cerebral Venous Thrombosis and Intracerebral Hemorrhage

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.

Early Seizures in Cerebral Vein and Dural Sinus Thrombosis Risk Factors and Role of Antiepileptics

Backgound and Purpose— The risk of seizure early after the diagnosis of cerebral vein and dural sinus thrombosis (CVT) is not known, and the use of prophylactic antiepileptic (AED) medication in the acute phase of CVT is controversial. Methods— In a multicenter, prospective, observational study, we analyzed the risk factors for seizures experienced before the diagnosis of CVT was confirmed (presenting seizures) or within the following 2 weeks (early seizures). The risk of occurrence of early seizures was compared in 4 risk strata and related to whether patients received AEDs or not. Criteria for the strata were “presenting seizures” and “supratentorial lesions.” Results— Two hundred forty-five of 624 (39.3%) patients with CVT experienced presenting seizures, and 43 (6.9%) patients had early seizure. In logistic-regression analysis, supratentorial lesion (odds ratio [OR]=4.05, 95% CI=2.74 to 5.95), cortical vein thrombosis (OR=2.31, 95% CI=1.44 to 3.73), sagittal sinus thrombosis (OR=2.18, 95% CI=1.50 to 3.18), and puerperal CVT (OR=2.06, 95% CI=1.19 to 3.55) were associated with presenting seizures, whereas supratentorial lesion (OR=3.09, 95% CI=1.56 to 9.62) and presenting seizures (OR=1.74, 95% CI=0.90 to 3.37) predicted early seizures. The risk of early seizures in patients with supratentorial lesions and presenting seizures was significantly lower when AED prophylaxis was used (1 with seizures in 148 patients with AEDs vs 25 in 47 patients without AEDs; OR=0.006, 95% CI=0.001 to 0.05). Conclusions— CVT patients with supratentorial lesions had a higher risk for both presenting and early seizures, whereas patients with presenting seizures had a higher risk of recurrent seizures within 2 weeks. Our results support the prescription of AEDs in acute CVT patients with supratentorial lesions who present with seizures.

Cerebral Vein and Dural Sinus Thrombosis in Elderly Patients

Backgound and Purpose— The clinical features and prognosis of cerebral vein and dural sinus thrombosis (CVT) in elderly patients have not been previously described. Methods— In a multicenter prospective observational study, we compared clinical and imaging features, risk factors, and outcome of adult patients aged <65 (young and middle-aged patients) and ≥65 years (elderly patients). Results— A total of 624 adult patients with CVT were registered and followed-up for a median of 16 months. Fifty-one (8.2%) were aged ≥65 years. Presentation as an isolated intracranial hypertension syndrome was less frequent in elderly patients (4/51 versus 139/573, P=0.008), whereas depressed consciousness (17 versus 97, P=0.005), and mental status changes (22 versus 115, P=0.001) were more frequent in the elderly. The prognosis of elderly patients was considerably worse than that of younger patients, as only 49% of elderly patients made a complete recovery (versus 82% in younger patients), whereas 27% died and 22% were dependent at the end of follow-up (versus 7 and 2% respectively in younger patients). Carcinoma (5 cases) was more frequent as a risk factor for CVT in elderly patients (P=0.017). During follow-up, elderly patients were more likely to experience thrombotic events (HR=4.8, 95% CI=1.9 to 11.9) and were less likely to experience severe headaches (HR=0.2, 95% CI=0.02, 0.97). Conclusions— Elderly patients with CVT have a distinctive clinical presentation: isolated intracranial hypertension is uncommon, whereas mental status and alertness disturbances are common. The prognosis of CVT is worse in elderly patients.

Seizures at the onset of subarachnoid haemorrhage.

In a prospective study of 253 patients with subarachnoid haemorrhage, 16 (6.3%) had seizures at the onset of bleeding. None had a previous history of seizures. One was an alcoholic. None had metabolic imbalance. Hemiparesis, Hunt’s grade >3, the amount of subarachnoid blood and the presence of an aneurysm were significantly more frequent in patients with seizures at the onset of subarachnoid haemorrhage. Although rebleeding and mortality or severe disability at discharge were more frequent in these patients, seizures were not a significant predictor of prognosis. One of the survivors with early seizures developed recurrent epileptic seizures 1 year later.