contact with the face, including trying to drink (hydrophobia). Hallucinations and fluctuating
consciousness proceed to coma, paralysis, and death within a week.
Diagnosis can be challenging. Presence of antibodies in serum (if unvaccinated) or CSF is
diagnostic but not terribly sensitive. Immunofluorescence can often detect virus in nerve twigs
surrounding hair follicles in skin biopsied from the nape of the neck. PCR has been used to
detect virus in saliva. Despite numerous attempts at treatment, only one or two individuals
have survived (24).
ENCEPHALITIS MIMICS
Mental status changes are common in many patients with systemic infections, particularly in
older individuals—typically in the absence of nervous system infection. Confusional states in
septic patients—even with sources as localized as urinary tract infections or pneumonia—are
so commonplace that clinicians rarely question the underlying pathophysiology. However in
some infections CNS changes can be disproportionately prominent; in these a number of
mechanisms may underlie these changes.
Patients with rickettsia [particularly Rocky Mountain spotted fever (RMSF)] and
ehrlichia/anaplasma (particularly human monocytic and granulocytic ehrlichiosis) infections
can have severe headaches and prominent mental status changes. In both, the disorder caused
by these intracellular organisms probably is less an encephalitis than an infectious vasculitis.
RMSF in particular can be associated with significant cerebral edema and stupor. CSF typically
demonstrates a modest lymphocytic pleocytosis and increased protein; CSF glucose is most
often normal. Autopsy studies demonstrate perivascular inflammatory infiltrates and
occasionally intravascular thrombi in the brain, pathologic changes that could easily explain
the seizures that sometimes accompany RMSF. Focal CNS findings are relatively infrequent in
patients with these infections and survivors typically do not have prominent neurologic
sequelae. Whether ehrlichia infections have significant neurologic involvement remains
unclear—although headaches and alterations of consciousness are described frequently, only a
few case reports have described focal brain abnormalities.
Diagnosis can be quite challenging. Organisms can sometimes be identified in buffy coat
isolates, using special stains. Serologic studies using immunofluorescence or ELISA can be
useful but titers may be negative very early in infection and often comparison of acute and
convalescent sera is necessary for diagnosis. Treatment with doxycycline is quite effective.
Legionnaire’s disease similarly does not infect the brain but causes altered cognitive
function with remarkable frequency—out of proportion to any associated hypoxia or other
metabolic abnormalities. This infection can often be suspected clinically by its multisystem
involvement—often with prominent early gastrointestinal symptoms (diarrhea and abdominal
pain), bradycardia, and hepatic and renal involvement. Diagnosis typically rests on the
combination of rapidly worsening changes on chest radiograms, and either serologic or
urinary antigen testing.
Patients with bacterial endocarditis similarly can have CNS manifestations related more
to involvement of the cerebral vasculature than of the brain itself. Signs and symptoms are
typically nonspecific—except when a septic embolism causes either a stroke or a mycotic
aneurysm that ruptures. CSF examination can demonstrate minor abnormalities. Diagnosis can
be quite challenging.
Similarly, noninfectious inflammatory disorders can affect the CNS—most prominently
CNS systemic lupus erythematosus. Again, findings are typically nonfocal; either on exam or
imaging, but cerebral edema can be prominent. Since many of these patients are on chronic
immunosuppression, one of the greatest diagnostic challenges can be differentiating between
insufficiently controlled lupus or a superimposed opportunistic infection in an immunocom-
promised patient.
DIAGNOSTIC APPROACH
Given the broad array of disorders, what is the most straightforward approach to the ill patient
with altered mental status? As illustrated in Figure 1, the first step is a clinical assessment,
focusing on the history. What were the earliest symptoms and how did the disorder evolve? If
neurologic involvement is evident from the outset (seizures, persisting focal deficits), the
Encephalitis and Its Mimics in Critical Care 161