Facial herpes zoster complicated by varicella zoster virus (VZV) encephalitis: The diagnostic significance of atypical lymphocytes in cerebrospinal fluid (CSF)

Abstract Background In general, viral infections of the central nervous system (CNS) manifest as encephalitis and, less commonly, as meningoencephalitis or aseptic meningitis. Varicella zoster virus (VZV) is an uncommon cause of encephalitis. Methods Herpes zoster (shingles) is a cutaneous reactivation of previous chickenpox infection due to VZV. Herpes zoster may be dermatomal (ie, 3 dermatomes). Decreased cell-mediated immunity from stress, steroids, or immunosuppressive drugs often precede dermatomal/disseminated herpes zoster. With herpes zoster, the closer the dermatomal involvement is to the CNS (ie, head/neck shingles), the more likely a patient will have symptomatic CNS involvement (eg, encephalitis). Except for the association of the herpes zoster rash and the simultaneous/subsequent encephalitis, there are few clinical features that distinguish VZV encephalitis from that due to other viruses. The cerebrospinal fluid (CSF) profile of VZV encephalitis is usually clinically indistinguishable from that due to of other causes of viral encephalitis. In VZV meningoencephalitis or encephalitis, the CSF typically shows a modest lymphocytic pleocytosis with normal CSF glucose levels, variably elevated CSF protein levels, and normal CSF lactic acid levels. Atypical lymphocytes are rare in the CSF with VZV encephalitis. Results We present the case of a 75-year-old woman who developed VZV encephalitis after having herpes zoster on her forehead. Except for facial herpes zoster, there were no clinically distinguishing features to determine the cause of her encephalitis. Her CSF had 800 white blood cells/high power field with 26% lymphocytes (17% atypical lymphocytes). The patient’s CSF glucose and CSF lactate dehydrogenase levels were normal, and her CSF protein was elevated. The CSF lactic acid was minimally elevated secondary to red blood cells in the CSF. Electroencephalogram showed general background slowing bilaterally, typical of viral encephalitis. The absence of unilateral focal frontotemporal/parietal lobe focus on electroencephalogram argued against the diagnosis of herpes simplex encephalitis. CSF atypical lymphocytes provided the key clue to the etiology of her encephalitis. CSF atypical lymphocytes are not uncommon in Epstein–Barr virus or cytomegalovirus encephalitis. Less commonly, atypical lymphocytes may be present in the CSF with enteroviruses, West Nile encephalitis, and Japanese encephalitis. VZV is a rare cause of atypical lymphocytes in the CSF but was the clue to the diagnosis before CSF polymerase chain reaction results for VZV were available. Her CSF polymerase chain reaction was negative for Mycobacterium tuberculosis, herpes simplex virus, human herpesvirus-6, cytomegalovirus, enteroviruses, and West Nile virus, but was positive for VZV. She made an uneventful recovery with acyclovir. Conclusion CSF atypical lymphocytes, if present, are an important diagnostic clue in some causes of viral encephalitis. The most common cause of nonseasonal viral encephalitis is herpes simplex virus, which is not associated with CSF atypical lymphocytes. Patients with Epstein–Barr virus, cytomegalovirus, West Nile encephalitis, and enteroviruses usually have extra-CNS signs and symptoms which should suggest the cause of the patient’s encephalitis. CSF atypical lymphocytes limit the differential diagnostic possibilities in patients with viral encephalitis and may be the key clue to the diagnosis, as in the case presented.