Valproic acid toxicity mimicking multiple system atrophy

Abstract

Recently, there have been several reports of unusual reversible neurotoxicity associated with valproic acid, including parkinsonism, cognitive impairment, and hearing loss.1-6⇓⇓⇓⇓⇓ We report a patient on long-term valproic acid treatment for epilepsy who developed a neurodegenerative condition mimicking multiple system atrophy that completely reversed on cessation of valproate. A 67-year-old woman was prescribed valproic acid in 1987 for post-traumatic generalized seizures. Over the subsequent 2 years, she had no seizures but developed imbalance, urinary incontinence, and mild cognitive impairment. A head CT scan showed enlarged ventricles and cerebral atrophy, so a ventriculoperitoneal shunt was inserted for suspected normal pressure hydrocephalus. She did not improve. Over the next 5 years, she developed memory loss, limited upgaze, resting tremor, increased tone, brisk reflexes, and bilateral extensor plantar responses. She continued taking valproic acid and for several months took levodopa without benefit. By 1995 she had dysarthria, …