Source: NEJM

Fever and Altered Mental Status

Posted by Sara Fazio May 17th, 2013

In the latest Case Record of the Massachusetts General Hospital, 76-year-old man with chronic renal disease was admitted to this hospital because of fever, worsening renal function, and confusion. Brain imaging revealed a small amount of material with restricted diffusion layering in the occipital horns of the lateral ventricles. Typical bacterial organisms that commonly cause acute meningitis in older patients are Streptococcus pneumoniae, Neisseria meningitidis, Hemophilus influenzae, and Listeria monocytogenes. The administration of empirical antimicrobial agents should be started before results of blood tests and culture of the cerebrospinal fluid are available.

Clinical Pearls
What tickborne infections are in the differential diagnosis of altered mentation? Infection with B. burgdorferi is more commonly associated with central nervous system infection than human granulocytic anaplasmosis (infection with Anaplasma phagocytophilum) or human monocytic ehrlichiosis (infection with Ehrlichia chaffeensis). Early disseminated Lyme disease typically occurs several weeks to months after the tick bite, and lymphocytic meningitis can be accompanied by cranial-nerve palsy. Rocky Mountain spotted fever (infection with Rickettsia rickettsii) can cause fever, thrombocytopenia, and lymphocytic meningitis. Most patients with this disease present with a rash, but the absence of a rash does not rule out the diagnosis, although it makes it less likely. What are the clinical manifestations of West Nile virus infection? Although 60 to 80% of patients infected with West Nile virus remain asymptomatic, West Nile fever develops in approximately 20% and is characterized by typical influenza-like symptoms of fever, myalgias, malaise, and anorexia. A maculopapular rash can appear in a quarter to half of patients and portends a lower risk for neuroinvasive disease. Patients with neurologic symptoms may have encephalitis, meningitis, or flaccid paralysis. Physical examination may reveal a coarse tremor, myoclonus, or such parkinsonian features as rigidity and cogwheeling.

Morning Report Questions

Q: How is West Nile virus infection diagnosed? A: A brief, low-level viremia occurs early in the course of many arboviral infections in humans; however, viremia is typically of short duration and overlaps with the asymptomatic period of clinical incubation. As a result, direct detection of arbovirus by nucleic acid testing is often no longer possible by the time a patient comes to the attention of clinicians. Therefore, serologic tests are the mainstay of diagnosis. Serum IgM is frequently detectable by the time patients with arboviral infections present for clinical care, and several days later, the IgG level becomes elevated. Patients may be seronegative if tested very early in the course of infection, so repeat testing of a convalescent-phase serum sample may be necessary if the diagnosis is strongly suspected. For patients with neuroinvasive disease, detection of virus-specific IgM in the cerebrospinal fluid (CSF) is also very useful; since IgM does not readily diffuse across the blood-brain barrier, finding it in the CSF suggests that antibody is being synthesized intrathecally in response to viral antigen that is present in the central nervous system. Q: What is the most common viral cause of meningoencephalitis? A: In general, herpes simplex virus type 1 is likely the most common viral infection leading to encephalitis. Depending on the season, arboviruses are not an uncommon cause of infection. During mosquito season in the eastern United States, West Nile virus, eastern equine encephalitis virus, St. Louis encephalitis virus, and La Crosse virus are in circulation. The largest outbreak of West Nile infection in recent U.S. history occurred in 2012, and approximately half of the cases were classified as neuroinvasive and 236 deaths were attributed to the virus that year. Typically, enteroviruses cause meningitis, but some types have been associated with encephalitis. Less common viral causes of encephalitis include human immunodeficiency virus, varicella zoster virus, and the mumps and measles viruses.