SEIZURES: SIGNIFICANT SIDE EFFECT OF CHLORAMBUCIL THERAPY

Abstract

Of 88 children with nephrotic syndrome treated with 96 courses of chlorambucil and prednisone, 6 (3 males, 3 females) experienced seizures during therapy. Diagnoses by renal biopsy were: focal segmental glomerulosclerosis (3), mesangial proliferative variant (1) and minimal lesion (1); one steroid responsive patient was not biopsied. The age at onset of disease ranged from 1.1-6.2 yrs, duration of illness from 0.4-8.5 yrs. The dose of chlorambucil varied between 0.18-0.67mg/kg/d for 8 days-13 weeks of treatment (total dose 1.6-36.7mgAg). In all, seizures were initially focal with progression to generalized myoclonus; 3 had multiple seizures while on therapy. No child had previous seizures while on steroid therapy alone except one who had a seizure with hypertensive encephalopathy 4 yrs previously. No child had hypertension, fever or metabolic abnormality at the time of seizures. Lumbar puncture in 4 was within normal limits. EEG showed focal changes in 5 and diffuse slowing in one; follow-up EEG in 4 had returned to normal. No child had persistence of seizure activity after chlorambucil discontinued. Even though seizure activity can not be related to age, duration of illness, sex, dosage, duration of treatment, or underlying disease, chlorambucil appears to be implicated as a contributing factor to these seizures.