Diazepam to improve acute stroke outcome: results of the early GABA-Ergic activation study in stroke trial. a randomized double-blind placebo-controlled trial.

BACKGROUND: We tested whether diazepam, a GABA-ergic drug that also inhibits brain nitric monoxide formation, improves acute stroke prognosis. METHODS: 880 patients, randomized within 12 h of acute stroke, received diazepam 10 mg or placebo by rectiole, as soon as possible, followed by 10-mg tablets twice daily for 3 days. Primary outcome was independence (Rankin score <3) at 3 months; secondary outcome was complete recovery (Barthel index >or=95 or Rankin score

Stroke and idiopathic Parkinson's disease: does a shortage of dopamine offer protection against stroke?

Data on the relationship between idiopathic Parkinson's disease (IPD) and stroke are conflicting. In this study, we examined the frequency of IPD in stroke patients registered in the Maastricht Stroke Registry. With the use of three different search strategies, we found eight individuals with IPD amongst a total of 1,516 stroke patients. We had expected to find approximately 30 IPD patients (relative risk 0.27; 95% confidence interval 0.11-0.53), based on IPD prevalence figures from a Dutch population-based study. We speculate that dopamine deficiency may protect against ischaemic brain damage, perhaps by reducing the effects of excitotoxicity.

Diazepam treatment to increase the cerebral GABAergic activity in acute stroke: a feasibility study in 104 patients.

In preparation of a trial on the neuroprotective effect of GABAergic activation by a benzodiazepine, we performed a feasibility study in 104 patients with acute (less than 24 h) stroke. 5 mg diazepam twice daily for 5 days (n = 44) was well tolerated, feasible, and appeared to be safe. Testing a dose of 10 mg twice daily for 5 days (n = 17) was stopped early because of drowsiness around day 5, interfering with regular patient care. A dose of 10 mg twice daily for 3 days was well tolerated, despite reported drowsiness in 12 of 43 patients. First-dose application by rectiole was feasible in 97% of the 104 patients. No blood pressure drop or respiratory arrest or insufficiency were detected, whereas the 2-week case fatality rate was similar to that of controls matched for age, sex, and stroke severity. We conclude that testing the GABAergic activity during the acute phase of stroke by 10 mg diazepam twice daily for 3 days is well tolerated and practically feasible, and it does not subject patients to an increased risk of potential serious adverse effects. Preparations for a large randomized trial are in a final stage.

Late seizures following a first symptomatic brain infarct are related to large infarcts involving the posterior area around the lateral sulcus.

Controversies exist concerning factors that contribute to the occurrence of epileptic seizures after stroke. Therefore, we studied prospectively the occurrence of seizures in 322 patients with a first-ever CT-confirmed symptomatic territorial brain infarct involving the cortex. We also studied potential risk factors for seizures, and gave special attention to cortical infarct location. Fifty-four patients developed post-stroke seizures. We distinguished between early- and late-onset seizures, occurring within two weeks following stroke-onset, or later than two weeks, respectively. We found that patients of 65 years or older with a cardioembolic brain infarct involving the middle temporal or post-central gyrus, had an almost eight times increased risk of early-onset seizures, whereas patients with a large brain infarct involving the supramarginal or superior temporal gyrus, had a five times increased risk of late-onset seizures. We conclude that risk factors and epileptogenic cortical areas for post brain infarct seizures can be identified, which however, differ between early- and late-onset seizures. These two seizure types may also differ in terms of seizure mechanism. Our findings may influence the decision on prophylactic treatment with antiepileptic drugs in stroke patients.

Is haemodynamical compromise a specific cause of border zone brain infarcts following cardiac surgery?

We evaluated the hypothesis that if hypotension or hypoperfusion is a major cause of border zone brain infarction, infarcts following cardiac surgery will be likely to be located in the vascular border zone areas, whereas cerebral perfusion would be lower compared with non-border zone infarcts. Ten of 37 patients with brain infarction following cardiac surgery had an infarct in one of the vascular border zones on CT. Haemodynamical characteristics and clinical features did not differ between border zone infarcts and remaining infarct subgroups. We conclude that compared with stroke series brain infarcts following cardiac surgery are more frequently located in one of the vascular border zone areas, but peri-operative haemodynamic compromise alone does not sufficiently explain this difference. Other possible mechanisms, such as showers of (micro-)emboli, should also be considered.

Silent brain infarcts in 755 consecutive patients with a first-ever supratentorial ischemic stroke. Relationship with index-stroke subtype, vascular risk factors, and mortality.

BACKGROUND AND PURPOSE: We wanted to establish independent associations of various clinical variables, computed tomographic (CT) scan features, presenting stroke subtypes, and outcome with the presence of silent infarcts on CT. METHODS: We studied 755 consecutive patients in a prospective registration of patients with first-ever supratentorial atherothrombotic, cardioembolic, or lacunar stroke or stroke of undetermined cause by multiple logistic regression analysis. RESULTS: Two hundred six patients (27%) with a first symptomatic territorial or small deep ischemic stroke had one or more silent infarcts on CT. Of all silent lesions, 169 (82%) were small and deep. Silent infarcts were significantly more strongly associated with a lacunar than atherothrombotic (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.02 to 2.47; P = .039) or cardioembolic (OR, 1.89; 95% CI, 1.2 to 2.99; P = .005) index stroke. Silent territorial lesions were more strongly associated with cardioembolic than with lacunar stroke but not with atherothrombotic stroke. In this respect, no differences were found between the atherothrombotic and undetermined-cause group. Advanced age and hypertension were the only risk factors that were significantly associated with silent infarcts (OR, 1.76; 95% CI, 1.14 to 2.71; P = .011; and OR, 1.58; 95% CI, 1.13 to 2.21; P = .007; respectively), mainly because of a strong independent association of these risk factors with silent small deep infarcts (OR, 1.75; 95% CI, 1.10 to 2.79; P = .018; and OR, 1.57; 95% CI, 1.09 to 2.24; P = .014; respectively). A cardioembolic source or atrial fibrillation in specific was not independently associated with any type or number of silent infarcts. Significant carotid stenosis (diameter reduction > 50%) was not significantly associated with any type of silent lesion. Initial severe handicap (Rankin Scale score > 3), 30-day case fatality rate, and 1-year mortality were not affected by the presence of silent infarcts. CONCLUSIONS: The strong association of silent small deep lesions with first symptomatic small deep infarcts suggests a common underlying mechanism (presumably small-vessel vasculopathy), whereas cardiogenic embolism and large-vessel thromboembolism are the most likely causes in both silent and first symptomatic territorial infarcts. Single or multiple silent infarcts do not predict a cardioembolic stroke mechanism in first symptomatic supratentorial brain infarcts. As silent infarcts do not predict the cause of carotid embolic stroke in first symptomatic brain infarcts, their presence should not influence the decision on carotid surgery. Silent infarcts do not affect the degree of initial handicap, 30-day case fatality, or 1-year mortality. The significance of silent infarcts for predicting possible future cognitive decline and risk of recurrent stroke deserves further study.

Isolated hemiataxia after supratentorial brain infarction.

Acute isolated hemiataxia is in most cases due to infratentorial (cerebellar) stroke. It has only twice been described in supratentorial stroke--namely, after thalamic infarction and a capsular haemorrhage. Three patients with isolated hemiataxia after a supratentorial brain infarct are described. These patients were seen in a period of five years during which 899 patients with a first supratentorial brain infarct were registered. Clinically the hemiataxia was of the cerebellar type. In two patients, CT and MRI showed a small, deep (lacunar) infarct restricted to the posterior limb of the internal capsule, a site not previously reported in isolated hemiataxia. The third patient had a small, deep (lacunar) infarct in the thalamus extending into the adjacent posterior limb of the internal capsule. Isolated hemiataxia after a supratentorial brain infarct is a very rare clinical stroke syndrome. The cerebellar type hemiataxia was most likely caused by interruption of the cerebellar pathways at the level of the internal capsule. Our cases confirm prior observations that the cerebellar pathways run through the posterior part of the posterior limb of the internal capsule separately from the motor and sensory pathways.

Cooperative study on the value of long term anticoagulation in patients with stroke and non-rheumatic atrial fibrillation.

The benefits of long term anticoagulant treatment of patients with non-rheumatic atrial fibrillation and cerebral infarction were studied by comparing two series of patients with stroke from centres with different policies on anticoagulant treatment. The long term prognosis of 50 patients from the Oxfordshire community stroke project, who did not receive anticoagulants, was compared with that of 70 similar patients from Maastricht, who were treated with anticoagulants. After a mean follow up of 27 months there was no significant difference in either the rate of survival or the rate of recurrent stroke between the two groups. These data suggest that any benefit of anticoagulation is modest. A large randomised trial is planned to establish whether long term anticoagulant treatment is of value and, if so, to what extent.