Jack A. Madsen

Lamotrigine High-Dose Tolerability and Safety in Patients with Epilepsy: A Double-Blind, Placebo-Controlled, Eleven-Week Study

Summary: Purpose: This study was undertaken to evaluate the dose tolerability and safety of a chronic ascending twice‐daily (b.i.d.) dosage regimen of 700 mg/day larnotrigine (LTG) and to include determination of the LTG pharmacokinetic profile at doses 500 mg/day in patients receiving concomitant enzyme‐inducing antiepileptic drugs (AEDs).

The coincidence of diffuse electroencephalographic spike-wave paroxysms and brain tumors.

PATIENTS with brain tumors occasionally have paroxysmal electroencephalographic dysrhythmias which resemble the three-per-second, spike and wave discharges of centrencephalic, petit ma1 epilepsy. “Secondary” subcortical epileptiform discharges of this type are thought to differ from those of “primary” subcortical epilepsy because of background irregularities, focal asymmetries, and slower spike-wave frequencies.’ Some authors emphasize, however, that patients with clinical petit ma1 frequently demonstrate atypical paroxysmal discharges and may show features which one cannot distinguish from secondary subcortical epilepsy.2-4 Other clinical criteria must be scrutinized to differentiate this important group from the less significant genetic form of epilepsy. Ajmone Marsan and Lewis, in 1960, reported two cases of brain tumor with diffuse spike-wave, electroencephalographic paroxysms and reviewed eleven others from the literature.5 Their analysis indicated that the phenomena were related to each other and not merely a chance coincidence of two different neurologic disorders. This report reviews the clinical, electroencephalographic, and pathological aspects of all reported cases and adds two additional cases. Although the pathogenesis of bilaterally synchronous spike and wave discharges is controversial, this review suggests that the electroencephalographic abnormality is related more closely to age than to other etiological factors.

Effects of SKF525A, Phenobarbital, Fasting, and Carnitine on the Anticonvulsant Activity and Neurotoxicity of Valproate in Mice

Summary: The anticonvulsant potency of valproate (VPA), as measured by the maximal electroshock seizure model in mice, was improved by pretreatment with the microsomal inhibitor SKF525A and by fasting, but was reduced by chronic phenobarbital pretreatment. Carnitine did not significantly alter the anticonvulsant properties of VPA. These findings suggest that the efficacy of VPA can be improved by factors that alter its metabolic pattern.

Interaction between phenobarbital and thioridazine

The effects of thioridazine (TDZ) on serum phenobarbital (PB) and phenytoin (PHT) were studied in mentally retarded persons. Persons taking these drug combinations were identified and matched on the basis of age, sex, body weight, and antiepileptic drug (AED) dosage with persons from the same population who were taking only the AEDs. Trough, steady state serum levels were obtained as part of regular AED monitoring schedules. Serum level of PB per unit dose was significantly less with concomitant administration of TDZ (100 to 200 mg/day) than when PB was given alone. This effect seemed to be TDZ dose-responsive. TDZ had no consistent effects on serum PHT.

Pilot study of fluzinaimide (N‐methyl‐3‐[3‐(trifluoromethyl) phenoxy]‐1‐azetidinecarboxamide) in refractory partial seizures

We conducted a pilot study of Auzinamide in 15 adults with refractory partial seizures. After a baseline period, fluzinamide was added to the existing regimen of phenytoin and carbamazepine and increased to maximum tolerated dose. Common side effects included dizziness, diplopia, ataxia, headache, nausea, and rash, resulting in patient withdrawal in six cases. Seizures became less frequent in four of the nine patients who completed the 8-week trial.