Abstracts

To correlate the appearance of phenobarbital (PB) withdrawal seizures in a patient with a decrease in the number of GABA[sub]A[/sub] receptors (GABAR) seen during PB withdrawal in PB-dependent rats., A patient, seizure-free for three years following removal of a cavernous angioma of her right anterolateral temporal lobe, had been taking PB for 11 years before surgery and was maintained on PB 150 mg/d for 3 years after surgery. The patient had a baseline of one psychic aura every two weeks. The decision was made to taper PB and to replace it with a non-inducing anti-epileptic drug. The patient kept accurate daily records of auras and seizures on a long-term continuous basis., A gradual reduction of PB was started and lamotrigine (LTG) slowly titrated, but typical complex seizures occurred when PB taper reached 60 mg/d. Conversion to LTG failed because of rash. PB was increased back to 90 mg/d and levetiracetam (LEV) was initiated and titrated to a dose of 500 mg BID. PB was then reduced by 15 mg every three weeks. When the patient was on PB 45 mg/d and LEV 500 mg BID, the frequency of auras increased, and LEV was increased to 750 mg BID. Seizures appeared when the patient was on PB 30 mg/d and LEV 750 mg BID. During the first week after PB was stopped and the patient was on LEV 1000 mg BID, there were 4 seizures. The seizures continued for 3 weeks after PB was stopped. After this time, there were no additional seizures and the dose of LEV remained constant at 1000 mg BID. The patient experienced anxiety and insomnia during the slow PB taper., This case demonstrates a [quot]threshold[quot] for PB withdrawal seizures at 45 to 60 mg/d and cessation of withdrawal seizures following PB discontinuation. At a dose of PB 90 mg/d, the patient had a plasma PB level of 11 mcg/ml. Assuming clearance did not change, withdrawal seizures appeared when the PB level was 5-8 mcg/ml. Withdrawal seizures were not controlled by LEV but ceased three weeks post complete withdrawal. Our data are explainable by a [quot]resetting[quot] of her GABAR. [³H]Muscimol binding to GABAR in rat brain homogenates was reduced by 25% in withdrawing animals for up to 10 days after chronic PB exposure (Tanaka et al., 1991). Similarly, there was a decrease in the [alpha]1 subunit of the GABAR in rat pups that had been exposed to PB for 30 days (Raol et al., 2005). Attenuation in the number of GABAR during PB withdrawal may account for the presence of PB withdrawal seizures in a patient who had been seizure-free. Termination of the withdrawal seizures may be associated with a resetting of the levels and types of GABAR.[figure1],