Abstracts

Rationale: Levetiracetam (LEV) is a widely used anti-seizure medication (ASM) approved for the treatment of focal and myoclonic seizures [1]. Its favorable properties include linear pharmacokinetics, lack of hepatic metabolism and protein binding, and lack of drug-drug interactions [2]. Adverse effects secondary to LEV are minimal, with fatigue, somnolence, headache, dizziness, and irritability being most frequently reported [2]. Dose adjustment of LEV is necessary in cases of renal impairment due to the drug’s predominant renal excretion [3].

Methods: We present a patient who developed multifocal myoclonus secondary to LEV toxicity in the setting of chronic kidney disease. Brain MRI and CT as well as extensive bloodwork were done. Daily clinical examination and continuous video-EEG monitoring demonstrated the finding reported herein.

Results: A 52-year-old woman with a past medical history of chronic kidney disease on hemodialysis, hypertension, and hypothyroidism was admitted to the George Washington University Hospital for cauterization following heavy vaginal bleeding secondary to a loop electrosurgical excision procedure. She suffered an intraoperative cardiac arrest with subsequent return of spontaneous circulation after 6 minutes. Thereafter, she had a witnessed seizure which was treated with Lorazepam 6 mg and Levetiracetam 1 g. Initial neurological examination revealed uprolling of eyes with occasional spontaneous blinks, increased tone in all extremities, withdrawal to a noxious stimulus in the right leg, and clonus in the left leg. Blood tests revealed elevated creatinine (5.7 mg/dL, clearance: 8.29 mL/min), elevated BUN (42 mg/dL), respiratory acidosis (pH: 7.31, pCO2 45.2 mmHg), and anemia (Hematocrit: 32.1%). Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) of the brain showed no evidence of acute intracranial pathology. Electroencephalogram (EEG) initially showed evidence of bifrontal seizures and lateralized periodic discharges (LPDs) culminating into non-convulsive status epilepticus that resolved after treatment with propofol, LEV 1500 mg BID, and lacosamide 200 mg BID. After one week of seizure freedom, ASMs were adjusted for renal dosing to LEV 500 BID and lacosamide 100 BID. Nonetheless, the patient developed multifocal myoclonus evidenced by muscle artifact in the right frontal and left occipital leads without ictal correlate on EEG. Levetiracetam toxicity was confirmed with a supratherapeutic level of 49.8 mg/dL. Myoclonus ceased concomitantly with discontinuation of LEV and normalization of drug levels.

Conclusions: While LEV has been shown to be an efficient anti-myoclonic agent, we describe a unique case which suggests that an excess of this medication can lead to a paradoxical effect. One may hypothesize a dose-dependent effect on myoclonus with more effective binding activation of SV2A receptors at low concentrations and possible quiescence at higher concentrations. Detailed review of additional cases of and risks of potential levetiracetam toxicity would be integral in further understanding its properties and mechanisms of action.

References
1) Abou-Khalil B. Levetiracetam in the treatment of epilepsy. Neuropsychiatr Dis Treat 2008;4:507–23.
2) Beran RG et al. Efficacy and safety of levetiracetam 1000–3000 mg/day in patients with refractory partial-onset seizures : a multicenter , open-label single-arm study. Epilepsy Res 2005;63:1–9.
3) Patsalos PN. Clinical Pharmacokinetics of Levetiracetam. Clin Pharmacokinet 2004;43:707–24.
4) Vulliemoz S et al. Levetiracetam accumulation in renal failure causing myoclonic encephalopathy with triphasic waves. Seizure 2009;18:376–8.

Funding: Please list any funding that was received in support of this abstract.: None.