Central Nervous System Infections

Encephalitis is a life-threatening inflammation of the brain parenchyma. Etiology is determined only in about half of cases, 20-50% of which are attributed to viruses.

Remember, patients with meningitis may be uncomfortable, lethargic, or distracted by headache, but in general, their cerebral function remains normal. On the other hand, abnormal brain function is a distinguishing feature of encephalitis, and patients can present with altered mental status, motor or sensory deficits, altered behavior and personality changes, and speech or movement disorders. This altered mental status can present in a number of ways, from subtle findings to complete unresponsiveness! To complicate things more, encephalitis can often present as an overlap syndrome with meningitis, which we label “meningoencephalitis.”



Clinically, however, encephalitis is defined as alteration in mental status lasting 24 hours or more that is associated with two or more of the following: fever, focal neurologic deficit, seizure, CSF pleocytosis, and abnormal findings on EEG. All patients should have neuroimaging to evaluate for a mass lesion or cerebral edema prior to LP and EEG. Unfortunately, despite thorough investigation, a specific cause is found in less than 50% of patients and most care is supportive. Start empiric acyclovir IV in all patients with encephalitis; once HSV is ruled out, this can be discontinued.

Let’s discuss some specific causes of encephalitis: (see the table below for an overview)

1)      HSV encephalitis: Herpes simplex encephalitis (due to infection with HSV-1) is by far the most common cause of encephalitis in the U.S. (50-70%). Most are a result of reactivation of latent virus. HSV encephalitis is characterized by unilateral or bilateral temporal lobe infection (MRI is more sensitive than CT at detecting this) although this is not necessary to diagnose HSV-1 encephalitis. CSF studies will classically show a lymphocytic pleocytosis. Check CSF for HSV PCR, which is greater than 95% sensitive and ~100% specific! (Keep in mind that sometimes the PCR can be negative early in infection so a repeat CSF specimen is often obtained for testing.) Viral culture is virtually useless (sensitivity of <5%) so don’t order it. HSV encephalitis is treated with acyclovir IV for 14-21 days.

2)      VZV encephalitis: Varicella-zoster virus (VZV) encephalitis can occur with acute varicella infection or with viral reactivation usually in immunosuppressed patients (HIV, patients receiving immunosuppressive therapy, etc.) VZV encephalitis is tricky: some patients may not have the characteristic skin lesions (sometimes CNS infection predates the lesions or the lesions don’t occur at all) and not all patients with the classic skin lesions have CNS involvement. VZV can also infect cerebral arteries, causing vasculitis, and presents as ischemic stroke rather than encephalitis! To confirm VZV involvement, send CSF for VZV PCR. Although there isn’t much data on VZV encephalitis treatment, treatment with acyclovir IV is recommended.

3)      West Nile neuroinvasive disease (WNND): The Aedes mosquito is the primary vector for WNV and most human infections occur in summer and early fall (when people are enjoying summer activities). Most infected people remain asymptomatic, with only 20% developing fever. The most severe presentation, WNND, luckily occurs only in <1% of infections with WNV. This can present as encephalitis, meningitis, myelitis or as an overlap syndrome and tends to be more prevalent in immunosuppressed patients and in adults over the age of 50. Limb weakness (which can be a single extremity or symmetrical) tends to be a unique characteristic—in severe cases, patient has acute flaccid paralysis that progresses to respiratory failure, similar to polio. Unlike the other two viruses, diagnosis of WNND is made with CSF serology, not PCR. Check CSF WNV serologies (specifically IgM), which is diagnostic of acute infection. Treatment is supportive.

Caution: there is serologic cross-reactivity between WNV and other flaviviruses (such as yellow fever, dengue, Japanese encephalitis virus and St. Louis encephalitis virus) so a positive serology test should be sent to your local public health department for confirmation!