Abstracts

Rationale: Seizures in Wilson’s disease (WD) are a rare occurrence. However, reports from centers specialized in the care of patients with WD, document a prevalence of seizures as high as 4-6%. Methods: We report a patient with WD who developed non-convulsive status epilepticus (SE) during chelating therapy with Tetrathiomolybdate (TTM) and review the last 20 years of the related medical literature (English or not). Results: A 55 year-old right handed man with WD (low serum ceruloplasmin 0.11 g/L; high 24 hour urine copper excretion 1.33 micromol/d; and bilateral K-F rings) with parkinsonian features and liver cirrhosis was admitted due to seizures. Seizures began on week 4 of treatment with TTM (Phase III Study of Dose Regimen in Neurological Wilson's Disease) Seizures were characterized by forced clonic eye and head deviation to the right followed by unresponsiveness, bilateral eye blinking and right hand automatism. EEG confirmed frequent clinical seizures arising from the left frontal region. Treatment was initiated with levetiracetam 1000mg BID but he developed non-convulsive status epilepticus with nonclinical seizures every 5-10 minutes as confirmed by Video-EEG. Seizures lasted 1-2 minutes each. Seizures were easily controlled within 24 hours with fosphenytoin, midazolam and levetiracetam. MRI of the brain showed diffuse brain atrophy, mineralization of the basal ganglia, and patchy FLAIR increase signal in the left frontal lobe. He was discharged on levetiracetam 1500mg BID and has remained seizure free. The most recent medical literature describes 6 patients with WD who developed SE but only 4 were available for review. Two of the patients developed SE at the presentation of the disease and before chelating treatment. Two patients developed seizures after a year of treatment with D-penicillamine. SE type was GTC in 3 cases. EEG showed epileptogenic foci in the left frontal in 2 cases, bifrontal in one and diffuse slowing in one. All MRIs had white matter lesions in both frontal lobes in addition to the findings related to mineralization of the basal ganglia. SE was treated with a combination of phenytoin and benzodiazepines in all cases. Conclusions: Non-convulsive status epilepticus is a very rare occurrence in WD. Our case is the only one reported in which SE developed during chelating treatment with TTM. Given the fact that SE developed in two patients prior to treatment with chelating agents, the pathophysiology of the seizures may not be related to specific chelating therapy but rather to copper neurotoxicity. There are no reports from specialized Epilepsy Centers about the incidence and prevalence of seizures and SE in patients with WD.