Case Presentation: A 75-year-old man with atrial fibrillation and no neurologic history presented to the emergency department with a one day history of somnolence, aphasia, and generalized weakness. He was nonverbal and minimally responsive to sternal rub. The patient had been diagnosed with herpes zoster in a thoracic dermatomal distribution two days prior to presentation and had been started on valacyclovir outpatient. The patient remained afebrile without headache, focal neurological deficits, or meningeal signs throughout the hospitalization. A stroke workup was initiated in the emergency room which included a negative computerized tomography (CT) head and negative CT angiogram head and neck; magnetic resonance imaging was deferred due to the patient’s pacemaker. An electrocardiogram revealed atrial fibrillation with a paced rhythm and echocardiogram revealed a normal ejection fraction with no intracardiac thrombus or atrial septal defects. His labs including urinalysis were unremarkable and his international normalized ratio was within therapeutic range. Electroencephalogram revealed the interictal expression of epilepsy. Lorazepam and levetiracetam were initiated and valacyclovir was discontinued per neurology recommendations. The patient’s mental status greatly improved and he was near his baseline status prior to discharge.
Discussion: Valacyclovir neurotoxicity can result in status epilepticus, altered consciousness, confusion, aphasia, or hallucinations within 72 hours of treatment, especially in patients with renal insufficiency. It is essential to rule out other etiologies such as meningitis, encephalitis, vascular causes, and neuropsychiatric disorders via imaging, EEG, and CSF analysis when diagnosing valacyclovir toxicity. Treatment includes prompt discontinuation of valacyclovir and hemodialysis in severe cases. In the case of valacyclovir-induced status epilepticus, phenytoin, benzodiazepines, and other antiepileptics are helpful. High dose valacyclovir predisposes to neurotoxicity. In the elderly population and patients with renal impairment, adequate hydration and a reduced dose should be considered due to renal elimination of valacyclovir.
Conclusions: Valacyclovir neurotoxicity should be considered in patients recently treated for herpes zoster, herpes labialis, herpes genitalis, or varicella zoster presenting with altered mental status, confusion, dysarthria, hallucinations, agitation, or seizures. Elderly population and renal impairment predisposes to valacyclovir neurotoxicity and dose adjustment is encouraged.