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CHAPTER 72: Encephalomyelitis 671

enhancement, diffuse hyperintense lesions, and ring-enhancing lesions, of febrile seizures. Reactivation of HHV-6 in immunocompromised
depending on the type of involvement. CSF is nonspecific and typi- persons, especially in hematopoietic stem cell transplant patients, has
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cally shows mixed pleocytosis, high protein and low glucose levels. been recognized as an important cause of limbic encephalitis, charac-
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The most specific finding is CMV DNA by PCR in the CSF. A high terized by short-term memory loss, seizures, and insomnia. 50,51 Focal
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level of CMV DNA in the CSF may be an indicator of significant CMV encephalitis with HHV-6 has been reported in immunocompetent hosts,
encephalitis. CSF viral cultures are often insensitive but very specific. but its role in causing encephalitis in immunocompetent hosts is unclear.
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CMV inclusions or cytomegalocytes with typical “owl eye” appearance Diagnosis can be made by PCR assay for HHV-6 DNA in serum, plasma,
are seen in 50% of patients. The diagnosis is especially challenging and CSF. CSF PCR has a sensitivity of >95%. The increased frequency
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in AIDS patients because the clinical presentation is widely variable of latent virus in the CNS lowers the positive predictive value, but a high
and there may be coexisting processes including HIV encephalopathy, CSF viral load may support the diagnosis of encephalitis due to HHV-6.
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toxoplasmic encephalitis, CNS lymphoma, or coinfection with HSV or Serologic assays for HHV-6 IgM antibodies are often unreliable.
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VZV. CMVE in immunocompetent individuals manifests similar to MRI of the brain may show hyperintense signal on T2 images of the
immunocompromised patients though they are relatively younger and medial temporal lobe. Intravenous administration of ganciclovir or
have better prognosis. Ganciclovir, an acyclic nucleoside analogue foscarnet is recommended for the treatment of HHV-6 encephalitis in
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of acyclovir, and its prodrug valganciclovir are the accepted antiviral immunocompromised patients and may be considered in immunocom-
agents of choice for CMV. The standard dose of ganciclovir is 5 mg/kg petent patients. 47
intravenously every 12 hours, given for 2 to 3 weeks. The dose should
be adjusted in patients with renal dysfunction. Ganciclovir should be ■ HERPES B VIRUS
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continued as a maintenance dose until the CD4 counts are maintained Old World primates (macaques) are infected with B virus and they
above 100 for at least 6 months. The main side effect of ganciclovir is remain lifelong carriers, asymptomatically shedding the virus. Human
bone marrow suppression. In AIDS and ganciclovir-resistant patients, infection occurs after exposure to saliva, genital, or ocular secretions
adding foscarnet or cidofivir may be considered. 44 or CNS tissue of infected monkeys. Human infection can result in fatal
■ EPSTEIN-BARR VIRUS encephalitis. Human-to-human transmission has also been reported.
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EBV is associated with infectious mononucleosis and a large number of Vesicular eruptions appear at the site of inoculation followed by flu-
like illness with fever, chills, myalgia, malaise, and headache. When
other illnesses and is transmitted through intimate contact with symp- the virus invades the CNS, patients may develop cranial nerve deficits,
tomatic or asymptomatic persons shedding the virus. The virus can be dysarthria, ataxia, hyperesthesia, agitation, seizures, and paralysis.
cultured from oropharyngeal secretions in about 10% to 20% of healthy After CNS symptoms develop, mortality is almost 100%. The diagnosis
asymptomatic adults. The incidence of asymptomatic shedding of the is made by viral detection by culture or PCR assay of vesicles at site of
virus is much higher in immunosuppressed persons. The majority of bite or serology by demonstrating a fourfold increase in convalescent
persons acquiring the infection have a subclinical illness or are asymp- stage antibody titers. Serologic testing is not helpful as there is antigenic
tomatic. CNS involvement as a complication of EBV infection occurs in cross-reactivity between herpes B virus and HSV-1 and HSV-2. The
less than 1% of cases. Neurologic complications reported are encephalitis, yield of CSF culture for the virus is low but PCR assay for the virus in
aseptic meningitis, transverse myelitis, Guillain-Barré syndrome, cranial the CSF can be performed. Treatment is prompt decontamination of the
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nerve palsies, optic neuritis, and peripheral neuritis. Most patients who wound inflicted by the monkey and starting prophylactic antiviral
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develop encephalitis present with features of acute mononucleosis, such therapy. Valacyclovir is the preferred agent and should be initiated at
as fever, pharyngitis, and lymphadenopathy. It is rare that the neurologi- the time of exposure and not delayed until symptoms develop. For
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cal manifestations are the only feature of EBV infection. Encephalitis may established disease without signs or symptoms of CNS involvement,
present as a rapidly progressive and severe illness with seizures, person- acyclovir, valacyclovir, or ganciclovir is appropriate. In patients with
ality changes and rarely may result in a coma. The majority of patients CNS symptoms, IV ganciclovir is recommended for a minimum of
with neurologic complications recover completely. The peripheral white 14 days or until all CNS symptoms have resolved. 47,56 Suppression
blood cell count may range from 12,000 to 18,000/µL with lymphocy- of latent infection with oral administration of valacyclovir may be
tosis. CSF analysis often reveals mononuclear pleocytosis with normal considered after treating an acute infection.
glucose and normal or slightly elevated protein concentration. Atypical
lymphocytes may also be present in the CSF. Heterophile antibodies in FLAVIVIRIDAE
the serum may be detectable either at the beginning or later during the
acute illness. Serologic testing for IgM antibodies to viral capsid antigen The viruses in this genus associated with infections of the central ner-
(IgM VCA) is highly specific and sensitive in the diagnosis of acute EBV vous system are Japanese encephalitis virus, West Nile virus, St Louis
infection. CSF PCR assay for EBV viral DNA may assist in the diagnosis encephalitis virus, Powassan virus, Murray Valley encephalitis virus,
of EBV encephalitis, but may give false-positive results. Therefore, a and Tick-borne encephalitis virus. They are zoonotic viruses and are
positive EBV PCR result in the CSF should be interpreted with caution, transmitted to humans by arthropods.
to support a diagnosis of EBV infection. T2-weighted MRI of the brain ■ WEST NILE VIRUS
taking into consideration other supporting clinical and laboratory data
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may show increased signal in the cortical white, gray matter and spinal West Nile virus (WNV) is a positive-stranded RNA virus in the family
cord. Treatment is supportive. The 2008 Clinical Practice Guidelines by Flaviviridae. It was first described in Uganda in 1937 and has made its
the Infectious Diseases Society of America do not recommend the use of way to North America in 1990s. Humans are infected through mos-
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acyclovir in the treatment of encephalitis due to EBV. With regard to the quito (Culex) bites. Most of the WNV infections are asymptomatic or
use of corticosteroids, the Society opined that such therapy may provide cause a mild self-limiting febrile illness. Less than 1% of infected patients
some benefit, but recommended weighing the potential risks against the develop neurologic disease manifesting as meningitis, encephalitis,
benefits. Successful treatment with IV ganciclovir has been reported in and poliomyelitis-like disease. WNV encephalitis presents with rapid
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immunocompromised patients with EBV encephalitis. 48 onset of headache, photophobia, back pain, confusion, and continued
■ HUMAN HERPES VIRUS 6 fever. Endemic areas, summer months, and mosquito exposure should
lead one to consider WNV infection. Diagnosis is by serology, WNV
Almost all humans are infected with human herpes virus 6 (HHV-6) antigen–specific ELISA, and IgM antibody–specific ELISA will confirm
by the age of 2 years. HHV-6 is associated with exanthema subitum infection. MRI is the imaging of choice and basal ganglia, thalami,
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(roseola), an illness in infants and young children that is a major cause brain stem, ventral horns, and spinal cord are commonly involved.

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