Abstracts

Hepatic dysfunction has only previously been reported once in the medical literature(1). We report here a patient with biopsy-confirmed eosinophilic hepatitis and hepatic dysfunction associated with the use of ethosuximide.
Case summary: A previously healthy cognitively normal 12 year old female was evaluated for refractory seizures consisting of sudden brief loss of postural tone in the right upper limb, both upper limbs, and/or head. EEG findings consisted of frequent hhigh amplitude diphasic left centro-temporal sharp waves significantly activated by sleep with otherwise normal background rhythms. Brain MRI scan was normal. Treatment with carbamazepine, oxcarbazepine, lamotrigine, topiramate, and levetiracetam failed to control episodes of apparent epileptic negative myoclonus. She was being treated with lamotrigine 250mg/day and levetiracetam 1350mg/day when a baseline ALT was 21 U/L prior to initiating a trial of ethosuximide. The lamotrigine was tapered off over 6 weeks while ethosuximide was advanced to 1000mg/day resulting in complete control of her epileptic negative myoclonus. Eight weeks after commencing ethosuximide therapy she bacame fatigued then developed slowly progressive nausea, anorexia, weight loss, abdominal discomfort, and ultimately recurrent vomiting.
An ALT was then elevated at 706 U/L. Serologies for hepatitis A,B, and C were negative. Epstein-Barr virus serologies were negative. CMV IgM titer was negative and her ANA was postive only at 1:40 speckled pattern with a negative anti-DNA antibody. Prior to her liver biopsy performed 11 weeks after beginning ethosuximide labs revealed: direct bilirubin of 2.1mg/dL, ALT 1885 U/L, AST 1487 U/L, LDH 2692 U/L, Alk Phos 465 U/L, albumin 4.0 mg/dL and prothrombin time was normal.
Liver biopsy revealed portal and periportal chronic active inflammation, eosinophilic infiltration, and hepatocellular degeneration and necrosis, multifocal giant cell transformation, hepatocellular and canalicular cholestasis, and portal fibrosis.
Ethosuximide and levetiracetam had been discontinued and the patient was treated with prednisone for four weeks followed by a four week taper. Her liver functin tests returned to normal within 3 months and have remained normal. She has remained free of epileptic negative myoclonus without anti-epileptic medication for the past 6 months and her wake and sleep EEG was normal 5 months after her medications were discontinued
One prior case of elevated AST to the 200 U/L range in a 1 year old which resolved after discontinuation of ehtosuximide has been reported. This child had previously been treated with valproic acid and phenobarbital and acetazolamide(1). Persistent gastrointestinal complaints in patients on ethosuximide may have causes other than local gastric irritation and should be considered and eliminated.
(1) Coulter DL. Ethosuximide-induced liver dysfunction. Arch Neurol 1983;40:393-394.