Case Presentation: An 87-year-old female with a history of end stage renal disease on hemodialysis (HD), presented to the ED with slurred speech, altered mental status, and generalized weakness for a day. At baseline she was alert and oriented to person, place, and time. Four days prior to admission, she was diagnosed with herpes zoster due to a significant a rash over her back and left hip. She was started on valacyclovir 500 mg three times a day. She received a total of 3 doses prior to development of neurological symptoms. On initial assessment, vital signs showed blood pressure of 190/96, afebrile and a normal finger stick glucose level. On physical exam, she was altered, with mild slurring of speech but no facial asymmetry or droop. Rest of the exam was unremarkable. She got a CT head and MRI brain per stroke protocol, which were negative for any acute intracranial process. Aspirin, high dose statin, and antihypertensives were started. Considering acute onset of neurological symptoms, negative stroke workup, and history concerning for acyclovir toxicity, she underwent emergent HD. Her symptoms improved with two rounds of HD and spinal tap was deferred. She was started on renally-adjusted dose of acyclovir for herpes zoster infection. No additional episode of toxicity was reported on follow up and improvement of herpes zoster infection was witnessed.
Discussion: Acyclovir and its prodrug valacyclovir, commonly used drugs for treatment of herpes are renally excreted. As a result, pharmacokinetics may be significantly affected by renal impairment, leading to toxicity. The direct effects of valacyclovir on the brain remain unclear, but high concentrations of valacyclovir may inhibit deoxyribonucleic acid polymerase, resulting in alteration of the mitochondrial function and subsequent neurotoxicity.Symptoms of neurotoxicity are usually seen after one to three days of starting the medication. Disturbances in the level of consciousness and confusion are the most frequently reported symptoms, followed by disturbances of perception, including hallucinations. Less commonly, neurotoxicity may manifest as ataxia, dysarthria, myoclonus, or rhabdomyolysis and in the most severe cases as seizures, coma, and death.It is very important to differentiate acyclovir neurotoxicity from herpes zoster virus-associated encephalitis, since the treatment of one will worsen the prognosis of the other. Encephalitis usually presents within one to two weeks from onset of vesicular skin eruption with symptoms of confusion and somnolence, although headache and fever are more common. History of presenting illness plays a pivotal role in differentiating the two diseases. Although, the mainstay of treatment for acyclovir neurotoxicity is stopping the offending drug, hemodialysis can also help in reducing the levels of the drug in bloodstream. It is an important tool for distinguishing between drug-induced neurotoxicity versus viral encephalitis.
Conclusions: Differentiating acyclovir neurotoxicity from herpes zoster virus associated encephalitis poses a diagnostic dilemma. A good history of presenting illness is vital to decide treatment plan. Extreme caution should be maintained while treating herpes zoster infection in patients with renal impairment.