Valproate for Treatment of Agitation in Neurosyphilis: A Case Report

Sir: The incidence of syphilis is low worldwide; however, its reemergence has been documented even in developed countries.¹ Developing countries like India and underdeveloped countries continue to have syphilis outbreaks on occasion.² Neurosyphilis with concurrent human immunodeficiency virus infection has raised fears of its recrudescence.³ Patients with the later stages of syphilis, especially neurosyphilis, may present with symptoms of virtually any psychiatric disorder.⁴ Here we report an interesting case of neurosyphilis presented to our psychiatric outpatient service.

Case report

Mr. A, a 55-year-old married man who lacked formal education and came from a lower socioeconomic, rural background, reported to our institute in November 2006 with an acute-onset illness of 1 year's duration characterized by irritable mood, restlessness, grandiose ideations, jocularity, disinhibition, decreased sleep, and demanding behavior in the initial 6 months followed by irritability, suspiciousness, and abusive, assaultive, and hallucinatory behavior (talking to self and smiling to self) for the next 5 months. In the last month, the patient had cognitive deficits (poor attention and concentration, immediate and recent memory deficits, impaired calculation, impulsivity, inability to recognize family members, and geographical disorientation), unprovoked aggression, agitation, unsteady gait, dysarthria, double incontinence, and inability to perform activities of daily living. He had received no treatment for the above symptoms. He had family history of chronic psychosis in a first-degree relative, personal history of high-risk sexual behavior, and nicotine dependence, and there was no significant past psychiatric/medical history. Premorbid personality was well adjusted.

On general physical examination, Mr. A had positive cortical release signs, brisk deep tendon reflexes, unsteady gait, dysarthria, and coarse tremors. Mental state evaluation revealed poor personal care; non–goal-directed restlessness and agitation; blunted affect; irrelevant speech; hallucinatory behavior; disorientation to time, place, and person; impaired attention and concentration; and impaired immediate and recent memory.

The patient was started on risperidone 2 mg/day, which was increased further to 3 mg/day for control of agitation and behavioral problems. Opinion from a neurologist was sought regarding his delirium. His serum and cerebrospinal fluid Venereal Disease Research Laboratory tests were positive in 1:16 and 1:2 dilutions, respectively. Trepanoma pallidum particle agglutination was positive in 1:20,480 dilutions. Computed tomography scan of the brain showed significant cortical atrophy with ex vacuo dilatation and subcortical hypodensities. Findings of other laboratory investigations were within normal limits. The diagnosis of neurosyphilis was made, and intravenous crystalline penicillin was started.

During treatment with risperidone 3 mg/day for 4 weeks, there was improvement in his psychotic symptoms, but there was no improvement in his agitation; hence, quetiapine 50 mg/day was started, which was increased to 400 mg/day because his agitation remained uncontrolled. The patient's agitation was not reduced during 4 weeks' treatment with quetiapine 400 mg/day, during which time he required frequent parenteral haloperidol 5 to 10 mg (at least once every 2–3 days) for management of agitation. He was then started on valproate 400 mg twice a day. There was marked reduction in the agitation and behavioral problems within 2 weeks, and the improvement was maintained throughout his stay in the hospital. At the time of discharge, Mr. A's behavioral problems and agitation had been reduced significantly, but his cognitive deficits remained the same.

Risperidone and quetiapine have been used in neurosyphilis for treating behavioral symptoms.⁵ However, in the present case both of the newer antipsychotics were ineffective in controlling behavioral symptoms. Valproate has been used successfully in treating agitation in dementias,⁶ delirium,⁷ and organic brain syndrome.⁸ In the present case, also valproate was able to decrease the agitation. There is evidence to suggest that valproate can bring down agitation very rapidly.⁹ This case report suggests that valproate can be used for controlling agitation in neurosyphilis.