A randomized double‐blind trial of prednisolone alone or with azathioprine in myasthenia gravis

Abstract

We compared prednisolone (PRED) and azathioprine (MA) versus prednisolone alone in the treatment of MG. Prednisolone alone or combined with azathioprine is widely used in the treatment of MG, but no randomized placebo-controlled comparative trial data are available. The prednisolone dose and clinical outcome were compared in a multicenter randomized double-blind study of 34 MG patients who were followed up for 3 years. One group (PRED + AZA) received prednisolone (on alternate days) plus azathioprine (2.5 mgkg); the other group received prednisolone on alternate days plus placebo (PRED + PLAC). Initial high-dose prednisolone (1.5 mgkg on alternate days) was tapered at remission to the minimal dose required to maintain remission. The prednisolone dose did not differ significantly between the two groups at 1 year (median values: PRED + MA, 37.5 mg on alternate days; PRED + PLAC, 45 mg on alternate days) but was reduced at 2 and 3 years in the PRED + MA group (median value at 3 years: PRED + AZA, 0 mg on alternate days; PRED + PLAC, 40 mg on alternate days; p = 0.02). Relapses and failures to remit over the 3 years were more frequent in the PRED + PLAC group. There was a sharp rise in the anti-acetylcholine receptor (AChR) titers in the PRED + PLAC group at 2 years. Incidence of side effects was slightly less in the PRED + MA group. Azathioprine as an adjunct to alternate day prednisolone in the treatment of antibody-positive generalized MG reduces the maintenance dose of prednisolone and is associated with fewer treatment failures, longer remissions, and fewer side effects.

Objective To analyze clinical, electrophysiologic, and neuroradiologic characteristics and prognostic factors in a group of patients with temporal lobe epilepsy (TLE) and complex partial seizures (CPS) occurring exclusively or predominantly after they fall asleep or before they awaken.

Background CPS arising during sleep are classically identified with frontal lobe epilepsy. TLE associated with seizures occurring only or predominantly during sleep (nocturnal TLE) is less common.

Methods From a series of patients with refractory TLE studied between 1980 and 1996, the authors identified 26 patients (15 men) with nonlesional nocturnal TLE (mean age, 40 years). Clinical and laboratory characteristics of these individuals were studied and compared with a group of 72 age-matched, randomly selected patients with nonlesional TLE and predominantly diurnal seizures (diurnal TLE).

Results Mean age at seizure onset was similar for both groups (16.3 versus 18.7 years). In the nocturnal TLE group, 2 of 26 patients had a positive family history of epilepsy, 18 reported an aura, 4 presented with CPS in clusters, 11 had unilateral and 15 bilateral temporal EEG abnormalities, and 14 of 21 studied had unilateral mesial temporal atrophy. None of these factors differed significantly in the two groups except for higher frequency of the following in the diurnal TLE group compared with the nocturnal TLE group: positive family history for epilepsy (33% versus 8%, p = 0.01), estimated frequency of seizures (median, 14 versus 2 per month; p < 0.01), and presence of antecedent febrile convulsions (33% versus 11%, p = 0.04). In the nocturnal TLE group, eight patients underwent surgical therapy and became seizure free (follow-up, >12 months). Only two were seizure free on medication. Conclusions: Infrequent and nonclustered seizures, rare family history of epilepsy, and low prevalence of childhood febrile convulsions characterize nocturnal TLE. Within the TLEs, the nocturnal TLE form seems to have a better surgical prognosis.