Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (112 page)

   Blood cultures are positive in approximately 10% of patients.

   Toxoplasma serology is recommended in patients with HIV infection. Other specific serologic testing is performed on the basis of epidemiologic risk.

   Laboratory findings due to associated primary disease.

ENCEPHALITIS

Encephalitis is a disease characterized by diffuse or localized inflammation of the brain parenchyma associated with neurologic dysfunction. Historically, viruses have been primary in the infectious etiology of encephalitis. Effective vaccination has reduced the incidence of several of the viruses that have been prominent causes of encephalitis, like mumps and measles viruses. The range of pathogens capable of causing encephalitis is broad. A specific diagnosis cannot be established in a significant number of patients with suspected infectious encephalitis. In patients in whom a diagnosis is established, approximately 70% are viral, approximately 20% bacterial, and approximately 10% other causes (prion, parasitic, fungal). Of note,
Mycoplasma pneumoniae
has been recognized as the cause of encephalitis in a significant proportion (approximately 30%) of children with encephalitis. Molecular testing is recommended; specific anti-
M. pneumoniae
serology was insensitive for detection. In addition, encephalitis and encephalopathy may be caused by a variety of noninfectious medical conditions.

A number of viruses are capable of causing encephalitis, either by direct infection or as an immune-mediated postinfection syndrome. Influenza; measles, mumps, and rubella; and varicella-zoster viruses have all been implicated in postinfectious encephalitis.

   
Herpes simplex virus
: HSV, usually type 1, is a common cause of sporadic encephalitis.

   
Arboviruses
(St. Louis, eastern equine, western equine, Venezuelan equine, West Nile): Arboviral encephalitis had been uncommon until the emergence of West Nile virus, which is now the most common cause of arboviral infection in the United States. These viruses show seasonal variability reflecting the distribution and activity of their mosquito vectors.

   
Rabies
: Rabies is uncommon in regions with effective vaccination programs, but low-level endemic infection is seen in host species inaccessible to vaccination, like bats and raccoons. Travel and animal exposure history are critical for timely diagnosis and treatment.

   
HIV
: HIV is neurotropic, and CNS involvement may result in a variety of types of neurologic dysfunction. In addition, severe immunosuppression associated with AIDS results in increased risk for opportunistic CNS pathogens, like CMV and JC virus.

   
Other viruses
: Encephalitis caused by other viruses is uncommon in the United States, but sporadic or epidemic encephalitis is seen in other countries caused by agents such as Arenavirus (lymphocytic choriomeningitis virus) and Nipah and Hendra viruses.

   Clinical Presentation

Patients present with headache, nausea, and vomiting; fever may be present. Patients usually develop changes in mental status, from subtle behavioral changes to frank obtundation. Seizures are common. Focal neurologic abnormalities may occur. Nuchal rigidity suggests a meningeal component (meningoencephalitis or isolated meningitis).

   Diagnosis and Laboratory Findings

Detailed history and physical examination are important in the assessment of patients. Some agents, such as rabies, may have restricted modes of transmission; other agents may show geographic restriction due to the range of the pathogen or intermediate vectors. Temporal lobe involvement suggests HSV infection. Preceding flaccid paralysis is suggestive of West Nile virus infection. Specific diagnostic testing should prioritize agents with the highest pretest probability based on presenting signs, symptoms, and epidemiology.

   CSF usually shows signs of inflammation, but these may be nonspecific. Findings overlap with aseptic meningitis and paraspinal abscesses. There is usually mild to moderate CSF pleocytosis (<250 cells/mm
³
), with lymphocyte predominance. The presence of significant numbers of RBCs suggests a necrotizing encephalitis, like HSV. Protein may be mildly elevated (<150 mg/dL). CSF glucose is usually not decreased (>50% of simultaneous serum glucose concentration).