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Reversible parkinsonism and cognitive impairment with chronic valproate use

From the Department of Neurology (Dr. Armon), Jerry L. Pettis Memorial Veterans Affairs Medical Center and Loma Linda University Medical School and Medical Center, Loma Linda, CA; the Department of Neurology (Dr. Shin), Mayo Clinic and Mayo Foundation, Rochester, MN; the Neurodiagnostic Center (P. Miller, S. Carwile, and E. Brown), Psychology (Dr. Edinger), and Audiology/Speech Pathology (Dr. Paul) Services, Department of Veterans Affairs Medical Center, Durham, NC; and the Department of Psychiatry (Dr. Edinger), Duke University Medical Center, Durham, NC.
Presented in part at: the 43rd annual meeting of the American Academy of Neurology, Boston, MA, April 1991; the 116th annual meeting of the American Neurologic Association and the 5th Symposium on Etiology, Pathogenesis and Prevention of Parkinson's Disease, Seattle, WA, September 1991; the 45th annual meeting of the American Epilepsy Society, Philadelphia, PA, December 1991; and the 44th annual meeting of the American Academy of Neurology, San Diego, CA, May 1992.
Received December 5, 1995. Accepted in final form February 21, 1996.
Address correspondence and reprint requests to Dr. Armon, Department of Neurology, Jerry L. Pettis Memorial Veterans' Affairs Medical Center, 11201 Benton Street, Loma Linda, CA 92357.

Following our initial report of the insidious development of reversible, valproate-induced hearing, motor, and cognitive dysfunction in two patients, we evaluated 36 patients in an epilepsy clinic who had been taking therapeutic levels of valproate for at least 12 months; 29 of these patients were examined according to a prospective protocol. We observed varying degrees of parkinsonism and cognitive impairment, from none to severe. Discontinuation of valproate in 32 affected patients led to subjective and objective improvement on follow-up testing at least 3 months later. Improvement was greatest in patients who were affected most. We conclude that a syndrome of reversible parkinsonism and cognitive impairment may develop insidiously in patients who have been treated with valproate for more than 12 months. The association with valproate may be overlooked due to the insidious onset.

NEUROLOGY 1996;47: 626-635

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