Refractory Idiopathic Absence Status Epilepticus: A Probable Paradoxical Effect of Phenytoin and Carbamazepine

Abstract

Summary: Purpose:To compare the frequency of seizures and status epilepticus and their response to first-line drugs in patients with idiopathic generalized epilepsies receiving carbamazepine or phenytoin to those receiving other drugs or no treatment.Methods: We performed a retrospective chart review of all cases of idiopathic generalized epilepsies treated by the authors between 1985 and 1994. We compared seizure frequency and mean intravenous benzodiazepine dose required to control absence status epilepticus, intraindividually in subjects on carbamazepine or phenytoin before and after discontinuation of these compounds, and interindividually to subjects without treatment or receiving other drugs.Results: Bouts of absence or tonic-clonic status epilepticus and seizures in subjects treated with phenytoin or carbamazepine at therapeutic concentrations were considerably more frequent and proved intractable to treatment with valproic acid or benzodiazepines, compared with a cohort of subjects also with idiopathic generalized epilepsies, but naive to, or receiving subtherapeutic or therapeutic doses of other agents.Conclusions: Our observations strongly suggest that therapeutic concentrations of phenytoin and carbamazepine exacerbate idiopathic generalized epilepsies. Subjects in whom absence is one of the seizure types seem at a particularly high risk for responding paradoxically. These findings underscore the value of accurate classification of seizures and particularly the syndromic approach to diagnosis and point to the potential for iatrogenic complications with indiscriminate use of antiseizure drugs. Key Words: Idiopathic generalized epilepsiesAbsence status epilepticus-Refractoriness-Paradoxical effects-Phenytoin-Carbamazepine.Convulsive status epilepticus refractory to appropriate treatment is well recognized and comprises a sizable percentage of all cases of status (1,2). In contrast, idiopathic generalized absence status epilepticus (IGASE), refractory to appropriate drugs, is rate (3-6). A survey of the literature revealed that complete control was attained in 93% of cases from 10 different studies (7).Paradoxical increases in seizure frequency is a recognized, but difficult-to-document, adverse effect of antiepileptic agents (8-10). The main limitation evident in the existing body of literature is a lack of systematic observations over reasonably long periods of time to minimize the confounding effect of the inherently high variability in seizure frequency, a phenomenon known as "regression of seizure frequency to the median" (9, I 1 ).In addition, the majority of reported cases have been patients with symptomatic epilepsy. We report eight carefully studied cases (Group 1) with idiopathic generalized epilepsy (ICE) on phenytoin (PHT) and carbamazepine (CBZ) with very frequent, seemingly intractable absence (AS) and tonic-clonic seizures who presented in absence status epilepticus (ASE) that proved refractory to intravenous high-dose benzodiazepines (BZDs). The lack of response in these cases was in star...

Nonconvulsive status epilepticus: a diagnostic and therapeutic challenge in the intensive care setting

“…The corresponding ictal EEG shows generalized spikewave discharges at a frequency of around 3 Hz [Baykan et al 2002;Kimura and Kobayashi, 1996]. Commonly, the condition is treated successfully by intravenous (iv) administration of 10 mg diazepam or 4 mg lorazepam [Osorio et al 2000;Thomas et al 1992;Tomson et al 1992]. Owing to the favourable response to first-line anticonvulsants, management of typical absence SE rarely requires ICU facilities.…”

Management of seizures in critically ill patients

“…The intravenous formulation of carbamazepine has been successfully used in animal models to control seizures [82], but has not been marketed yet in the United States. Carbamazepine can exacerbate the nonconvulsive seizures of the Lennox-Gastaut syndrome in childhood or induce myoclonic, partial [83], or absence SE [84,85]. This situation can be particularly resistant to treatment with other AEDs, can cause increased intracranial pressure or transient magnetic resonance imaging abnormalities [85], and can only respond to withholding of the drug [83].…”

The Etiology and Diagnosis of Status Epilepticus

“…Intravenous valproate has been used in pediatric epilepsy patients with refractory SE (67). In absence or idiopathic myoclonic SE, carbamazepine or phenytoin may provoke generalized SE (68) and earlier substitution with valproate may be successful (69).…”