James Zisfein

Single-Dose Oral Phenytoin Loading

A single 18 mg/kg dose of oral phenytoin capsules or suspension (mean dose, 1.3 g) was given to 44 patients with recent seizures and no detectable serum phenytoin level. Mean serum phenytoin levels after loading for patients receiving capsules were 6.8 micrograms/mL at two hours, 9.7 micrograms/mL at three to five hours, 12.3 micrograms/mL at six to ten hours, and 15.1 micrograms/mL at 16 to 24 hours. Mean levels for patients receiving suspension were slightly, but not significantly, lower than for patients receiving capsules. No seizures occurred during an eight-hour observation period after loading. Drug toxicity was minimal. Single-dose, 18 mg/kg oral phenytoin loading provides rapid therapeutic levels and is well tolerated.

Combination valproate—carbamazepine therapy in partial epilepsies resistant to carbamazepine monotherapy

Eighteen patients with poorly controlled partial epilepsy on carbamazepine monotherapy at maximum tolerated doses were treated with valproate adjunctive therapy. Both medications were maintained for at least 3 months at the highest tolerated doses. Three patients had >50% decrease in seizure frequency on bitherapy; six patients were moderately improved, with a 22–44% decrease in seizure frequency; the remaining nine patients were unchanged or worsened; with up to a 49% increase in seizure frequency. Five of six patients with more than four seizures per month improved on bitherapy. Four patients had a shift of predominant seizure type from tonic—clonic to complex partial; two of these patients were moderately improved and two had an overall increase in seizures. Clinical toxicity was common on bitherapy, managed by a reduction in carbamazepine dose in most patients. We conclude that valproate—carbamazepine bitherapy may be beneficial in approximately half of patients who have failed high-dose carbamazepine monotherapy; however, marked improvement is infrequent. Valproate—carbamazepine bitherapy is also frequently associated with clinical anticonvulsant toxicity at the beginning of bitherapy, but this is generally easily managed with medication adjustment.

Use of CT in epilepsy : does it matter how long you wait ?

Computer tomography (CT) of the brain is of value for finding potentially correctable lesions in adult patients with new onset seizures. The value of CT is unknown, however, for finding such lesions in adult chronic epileptic patients without prior CT. We compared a group of 177 adult patients who had CT within a year from the onset of seizures to a group of 93 patients who had a history of seizures for more than a year before CT was performed. In the first group, 33 potentially correctable lesions (19%) were found including 17 tumors. The group with chronic epilepsy had 4 (4%) potentially correctable lesions: 3 arteriovenous malformations and 1 meningioma. It seems that CT is of value in discovering potentially removable lesions in chronic epileptic patients, but the likelihood is relatively small. The incidence of stable structural lesions seems to be similar in the two groups.

Single-dose oral phenytoin loading is superior to divided-dose loading**

Phenytoin (PHT) loading is indicated for acute seizure prophylaxis. Oral loading is safer than intravenous loading but is slower and less reliable. Oral PHT loading has historically been accomplished in several divided doses because of concerns about toxicity and the possibility of delayed or incomplete absorption of a single large dose. Single-dose and divided-dose PHT loading have not been compared previously in a controlled clinical study. We randomized 54 emergency department patients in need of acute seizure prophylaxis to singledose or divided-dose loading. All patients received a total dose of 20 mg/kg extended PHT capsules. The divided-dose patients received four equally divided doses in 9 h. At 3 h after the first loading dose, 48% of the single-dose patients had therapeutic levels of ⩾10.0 mg/L as compared with 5% of divided-dose patients. At 6 h, 68% of the single-dose patients had therapeutic levels as compared with 24% of divided-dose patients. Adverse effects were mild and were similar in both groups. We conclude that oral PHT loading for acute seizure prophylaxis should be accomplished in a single dose