For refractory SE, intravenous propofol, midazolam, or pentobarbital have been used.106 Propofol and midazolam are preferable to pentobarbital in most stroke patients, who are more prone to hypotensive effects because of age and comorbidity. Drug-induced coma with these agents is also a consideration in refractory complex partial SE.
Eclampsia and other hypertensive conditions
For acute seizures due to eclampsia, phenytoin and benzodiazepines may have a role, but recent studies suggest that intravenous magnesium is the mainstay of treatment.25,26 One regimen is a 4-g load, followed by continuous infusion of 2–4 g per hour, to maintain a level of 4–8 mg/dL without losing deep tendon reflexes and muscle strength.
Whether this regimen should also be used in hypertensive or immunosuppressant-related posterior leukoencephalopathy is not known. When hypertension is clearly a causal factor, rapid control of blood pressure using labetalol or nitroprusside is recommended.
Stroke treatments sometimes need to be modified because of the coexistence of seizures or the use of AEDs. The enzyme-inducing AEDs (phenytoin, carbamazepine, phenobarbital) produce major increases in warfarin , so that warfarin doses must be adjusted when these AEDs are initiated or withdrawn, or when major dose changes are made.
Furthermore, warfarin may be contraindicated if seizures are not completely controlled and sometimes result in falls. This is a concern mainly in patients with atrial fibrillation, the best-supported indication for anticoagulation. Alternative treatments, such as adjusted subcutaneous heparin or low-molecular-weight heparin preparations, are likely to pose similar risk of serious bleeding in those prone to falls or other . Antiplatelet agents have lower risk but also lower in stroke prevention for those with atrial fibrillation. Antiplatelet agents must be used with caution in patients on valproate.
For those undergoing surgery, including endarterectomies, aneurysm clipping, or resection of a vascular malformation, postoperative changes in absorption and metabolism of AEDs must be considered. Medications with intravenous formulations do not pose a problem, as doses are equivalent to the oral forms. Medications without parenteral forms generally can be given via a nasogastric tube, but only if the gastrointestinal tract is functional. Pharmacies can prepare suppositories for rectal administration in some cases, as for carbamazepine.
An alternative is temporary administration of an alternative drug intravenously. For example, 1 mg of lorazepam two or three times daily can provide adequate antiseizure coverage in many cases for 1 or 2 days. If longer parenteral administration is required, phenytoin is a reasonable alternative.
Postoperative metabolic changes are another consideration. Phenytoin levels fall after general anesthesia, and carefully following levels and giving boluses as needed can prevent seizures in this setting. Carbamazepine levels may fall initially, either because oral doses are missed or because absorption is decreased, but on the next day the levels may sometimes rise significantly. Clinical toxicity often does not occur, however, because the increase may be due to diminished conversion to the somewhat more toxic epoxide .
Folate and homocysteine levels
Another potential issue is the recent observation that many AEDs not only decrease folic acid levels, but also increase levels of homocysteine, a recently identified risk factor for stroke.107 A surprising finding was that this effect was not limited to the older enzyme-inducing AEDs, which that are known to increase folate metabolism, although the numbers of patients taking newer medications were small. The effects were larger in older individuals and in men. Although most patients had folate and homocysteine levels in the normal range, there may still be implications for stroke risk.
A final consideration in modifying stroke treatment when patients have seizures concerns the unusual condition of vasculitis. Hepatic enzymes metabolize the immunosuppressant drugs used to treat these conditions, including cyclosporine A and corticosteroids, and doses may need to be increased when inducing AEDs are added. Furthermore, cyclosporine A can lower the and must be used with caution in seizure patients.
Adapted from: Bromfield, EB, and Henderson GV. Seizures and cerebrovascular disease. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;269–289.
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