ventriculoencephalitis and dementia in the immunocompromised. HSV6 can cause enceph-
alitis similar to HSV1 and has been associated with febrile seizures in infants. Ebstein–Barr
virus has been associated with a similar clinical picture, but has not been shown to respond to
acyclovir or other antivirals.
West Nile Virus
With over 1,200 cases of neuroinvasive disease in 2007 (21), West Nile virus is now probably
the commonest cause of encephalitis in the United States (with virtually the same number of
cases as there are due to HSV1). Unlike herpes, West Nile is one of the large group of diseases
referred to as arthropod borne, or arboviruses. These agents, which include the equine
encephalitis viruses, Venezuela, St. Louis, and others, share the ability to infect multiple
species. West Nile appears to have been brought to the United States by infected birds and was
originally recognized for being highly lethal in some but not all bird species.
Key to the transmissibility of any of these infections is its production of prolonged
viremia in some host species, and the presence of mosquitoes or other vectors that feed on both
the infected reservoir species and on humans (22). This interspecies promiscuity is essential to
the transmission of this large group of pathogens, which can persist in the environment in
reservoir hosts, and periodically infect humans when a large group of nonimmune individuals
is exposed. Since there are hundreds of asymptomatic or minimally symptomatic infections for
every neuroinvasive case, “herd immunity” normally takes over after the infection is present in
the environment for a period of time—presumably the reason the incidence of cases has moved
like a wave across the United States from east to west since its initial introduction.
West Nile is a flavivirus (the family that includes and is named for Yellow Fever virus), a
broad group that includes dengue, tick borne encephalitis, Japanese encephalitis, and St. Louis
encephalitis viruses. It was first detected in North America in 1999. In the Middle East, serologic
studies indicate up to 40% of the population has had asymptomatic infection. Studies in the
United States suggest 80% of infections are asymptomatic with most of the remainder developing
nonspecific symptoms with fever, head and back pain, and GI symptoms all occurring with some
frequency. Neuroinvasive disease develops in fewer than 1% of infected individuals. Mortality
among these is about 10%. Disease severity increases with age, with most mortality occurring in
individuals over 50. Over half the survivors of neuroinvasive disease have sequelae (22).
Neuroinvasive disease causes meningitis; a polio-like syndrome of flaccid lower motor
neuron–type weakness occurs in about half. Involvement of the brainstem and basal ganglia
appears to be common with extrapyramidal syndromes, tremors and ataxia occurring with
some frequency. Patients often have a peripheral leucopenia and CSF lymphocytosis.
Diagnosis is by serologic testing [IgG (immunoglobulin G) and IgM (immunoglobulin M)
antibodies in serum and CSF] and PCR. MRIs have shown abnormalities in the spinal cord,
brainstem, and basal ganglia. No specific treatment is available.
Rabies
Fortunately human rabies is extremely rare in the United States, with typically 1 case per year
nationwide. However there is a significant incidence among animals, and when human cases
occur, there often is some delay in diagnosis, resulting in additional individuals being
exposed, and then requiring prophylaxis. This too is a zoonosis, existing in innumerable
mammalian species. Transmission requires transfer of virus-containing secretions or tissue
through mucosa or broken skin. Since the virus has an affinity for the muscle endplates,
infection is particularly efficient when a bite introduces the virus directly into muscle. Once
introduced, virions are transported within axons to the dorsal root ganglion neurons and
multiply, then on to the spinal cord and brainstem. This asymptomatic incubation period lasts
weeks to years (23). Once the virus is in the nervous system, patients develop fever, anxiety,
muscle aches, and nonspecific symptoms. Neuropathic symptoms ranging from itching to pain
may develop at the inoculation site. Ultimately patients develop either paralytic rabies or the
encephalitic form. In the former, patients develop a Guillain Barre–like picture, with fever,
sensory and motor symptoms, facial involvement, and sphincter dysfunction. More common is
the encephalitic form in which patients develop inspiratory spasms, precipitated by any
160 Halperin