Objectives: To define the clinical characteristics of acyclovir neurotoxicity and to outline how to distinguish it from viral encephalitis.
Design: Case series of acyclovir neurotoxicity.
Setting: All cases reported in Index Medicus or in bibliographic reviews of acyclovir neurotoxicity plus two representative studies of Varicella zoster and Herpes simplex virus encephalitis.
Subjects: Thirty-five patients who developed neuropsychiatric symptoms during acyclovir therapy.
Interventions: Analysis of the patients' demographics, risk factors, acyclovir dosages and duration, clinical and laboratory findings and outcome.
Main outcome measures: All clinical and laboratory findings that were statistically significantly different from viral encephalitis.
Results: The median age was 53.3 years. The most common predisposing factors were the use of other potentially neurotoxic medications (17 cases) and acute or chronic renal failure (15 cases). Acyclovir levels were frequently found above the therapeutic range. The characteristic manifestations were confusion (15 cases), hallucination or delirium (9 cases), agitation (8 cases) and lethargy (10 cases). Few patients had associated tremors (11 cases). Fever, headache, seizures and focal neurologic findings were distinctly rare. Cerebrospinal fluid and computed tomography were normal except in patients with other central nervous system disorders. Symptoms appeared within 2 days of therapy in the majority and resolved completely within several days of discontinuing acyclovir.
Conclusions: Acyclovir neurotoxicity is a self-limiting, dose-dependent phenomenon which is more common in the elderly, in patients with renal failure or in association with other neurotoxic medications. It is distinguished from viral encephalitis by its sudden onset, absence of fever or headache, lack of focal neurologic findings and normal cerebrospinal fluid.