A 5-year-old female child with valproic acid (VPA)-related alteration of consciousness and brain atrophy that progressed over a 3 day period and resolved within 12 hours of discontinuing VPA is reported from Dokkyo University School of Medicine and Shimotsuga General Hospital, Tochigi, Japan. Seizures began at 2 years of age, EEG showed bilateral temporal and central focal spikes, and treatment with VPA (15 mg/kg/d) was effective until a generalized clonic seizure occurred at 5 years. CT was normal, VPA serum level was 25.7 mcg/mL, and the dose was increased to 20 mg/kg/d, resulting in a serum level of 76.4 mcg/mL. After 3 months on this dose and over a period of 3 days, she developed an alteration of consciousness. She had difficulty stating her name and had little interest in her surroundings. Neurologic examination, liver function tests and serum ammonia were normal. VPA level was 107 mcg/mL, the CT showed enlargement of cerebral sulci and evidence of brain atrophy, and the EEG awake revealed diffuse background slowing. VPA was discontinued, and consciousness level returned to normal within 12 hours. After 1 week, a repeat EEG was normal, and serial CT showed improvement within 1 month and normal appearance in 2 months. Phenobarbital was substituted, and at 5 month follow-up, her behavior and mental function were normal. [1]

COMMENT. Reversible dementia and pseudoatrophy of the brain associated with valproate treatment have been reported previously (McLachlan RS (1987), Papazian O et al (1995), and Guerrini R et al (1998) - authors’ citations). The differential diagnosis includes VPA-related encephalopathy with hyperammonemia, mitochondrial disorders, cytochrome c deficiency, carnitine deficiency with hepatic failure, and paradoxical VPA-induced status absence. Changes in consciousness during treatment with VPA should suggest possible drug toxicity and reversible cerebral atrophy.

The safety and efficacy of IV valproate in pediatric status epilepticus is reported in 18 patients from Harbor-UCLA Medical Center, Torrance, CA [2]. All 18 patients regained baseline mental status within 1 hour of seizure cessation. Post-infusion plasma VPA levels ranged from 51 to 138 mcg/ml.