Trimethadione (Tridione) Nephrosis

Abstract

Trimethadione (Tridione) was first shown to be highly specific in petit mal epilepsy by Perlstein in 1946, and this has been amply confirmed by Lennox and others.1 It was recognized early that toxic side-effects may follow prolonged administration of the drug, such as dermatitis, hepatitis, photophobia, drowsiness, nausea, aplastic anemia, and agranulocytosis. Barnett and co-workers2 reported the first case of nephrotic syndrome following the use of trimethadione in 1948. Since then, four more cases have been reported with one death.3-5,7 One case followed the use of paramethadione (Paradione),6 a related drug. We are adding two additional cases of nephrosis following the trimethadione treatment for petit mal, both of which ended fatally. Report of CasesCase 1.\p=m-\Thiswas the first Maimonides Hospital admission of a 6-year-old white boy, who entered the hospital in coma on May 12, 1951. Four days prior to his admission the mother first noticed some swelling of the eyelids. After 48 hours this swelling disappeared. On the following morning edema was again evident, this time in¬ volving the entire face and the extremities. On the next morning, the fourth day of illness, the child appeared to be in coma. A urine examination at this time revealed a 4+ albuminuria. A diagnosis of nephrosis was made, and the child was admitted promptly to the hospital.Past History.-The patient was born at full term and had a spontaneous delivery. At about the third to fourth month of life, some suspicion was aroused that development was not proceeding normally. At about 11 months of age, the first convulsion occurred. A diagnosis of cerebral palsy with mental deficiency was made at that time. Convulsions at first were generalized, but after several months they became milder and resembled petit mal, occurring several times a day and con¬ sisting of stiffening of the body with momentary loss of consciousness. At 4 years of age trimetha¬ dione was started. Blood counts were done regularly every month throughout the period of observation. About six months before admission, urine exam¬ ination was performed and found to be normal.Family History--Both parents were alive and well. There was no history of familial or hereditary diseases.Physical Examination.-Examination revealed a well-nourished, well-developed child in coma. Tem¬ perature, pulse, and respirations were normal. Blood pressure was 135/86 mm. Hg. The face, especially around the lids, was moderately edematous. There was no abnormality of the ears, nose, and throat. The lungs were clear to percussion and auscultation. The heart was not enlarged to percussion. The point of maximal impulse was not seen or felt. There was a regular sinus rhythm, and no murmurs were heard. The abdomen revealed no evidence of ascites. The liver and spleen were not palpable, and no masses were felt. There was moderate spasticity of all extremities, especially marked on the left side. The left knee jerk was more active than the right. Babinski and ankle clonus signs were not elicited. Moderate edema was...

Clinical pharmacology of anticonvulsant compounds

“…A nephrotic syndrome and other nephrotoxic effects of trimethadione have been reported. s4 , 104 More recently, alopecia has been reported as a reversible side effect of trimethadione therapy. 55 The substitution of a less toxic but related single agent such as paramethadioneo generally offers the patient much less effective therapy.…”