Termination of absence status epilepticus by low‐dose intravenous levetiracetam

Abstract

To the Editors: There is increasing data to support the efficacy and safety of levetiracetam (LEV) in the treatment of idiopathic generalized epilepsies (IGE) (Grünewald, 2005; Berkovic et al., 2007). However, the successful use of oral or intravenous (i.v.) LEV in patients with IGE presenting with absence status epilepticus (ASE) has not been reported to date. In a 37-year-old male, history and video-EEG disclosed IGE with the first manifestation of a generalized tonic-clonic seizure at the age of 27 years and frequent ASE with cognitive impairment of mild to moderate severity lasting up to several days. Previous antiepileptic medication included valproic acid, lamotrigine, topiramate, and zonisamide, but not LEV. After withdrawal of antiepileptic drugs during video-EEG monitoring, a habitual ASE occurred which was characterized by subtle but consistent attentional and executive disturbances as well as a cognitive slowing of fluctuating albeit gradually augmenting intensity. The patient was still responsive and showed good recollection of ictal events. The EEG displayed discontinuous generalized 3–5 Hz sharp-slow-wave-complexes. The number and the duration of these epileptiform potentials substantially increased in the course of the ASE. About 19 h after the clinical onset of ASE, neuropsychological examination by the Trail Making Test A and B (Reitan, 1992) revealed a marked reduction of cognitive speed and mental flexibility. Generalized epileptic activity was present in up to 60% of the time on surface EEG. The patient eventually stated that the subjective strain was no longer tolerable. We therefore administered 500 mg i.v. LEV within 5 min. After 20 min, additional 500 mg LEV was infused over 15 min. After the administration of the first 250 mg i.v. LEV, the patient reported a substantial relief; and after infusion of 500 mg LEV, he felt that he was back to his normal self. Repeated neuropsychological examination after i.v. administration of 500 and 1,000 mg LEV revealed a dose-dependent improvement in cognitive performance, which finally reached a normal level after application of 1,000 mg i.v. LEV (Fig. 1A and 1B). Accordingly, a ddose-dependent reduction down to baseline values of both the number of the generalized epileptiform potentials and the total of their duration was observed (Fig. 1C and 1D). The clinical and electrophysiological effects of i.v. LEV were sustained without any relapse during the following 6 h of observation. There were no adverse reactions. Dose-dependent and sustained effects of i.v. levetiracetam (LEV) on neuropsychological performance (A and B) and EEG (C and D). Onset, initiation of administration of i.v. LEV during absence status epilepticus; TMT, Trail Making Test, indicator of cognitive speed (TMT-A) and flexibility (TMT-B); ETP, generalized epileptiform potentials (mean values based on measurements of 5 min, besides 1 min measurement after administration of 250 mg i.v. LEV). ASE is a prolonged nonconvulsive state of ongoing or intermittent epileptic activity with cognitive or behavioral changes. Established therapeutic options include the i.v. administration of a benzodiazepine or valproic acid (Kaplan, 2005; Shorvon & Walker, 2005). However, sedation or respiratory depression is not uncommon after administration of benzodiazepines. In our patient with IGE, low-dose i.v. LEV led to an immediate and sustained interruption of a prolonged ASE without any undesired side effects. As reported in complex focal status epilepticus in focal epilepsies (Knake et al., 2008; Schulze-Bonhage et al., 2007), also in IGE the administration of i.v. LEV may be an effective and well-tolerated alternative to benzodiazepines in the treatment of nonconvulsive status epilepticus. Conflict of interest: We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. None of the authors has any conflict of interest to disclose.