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Febrile Illness With Neurologic Complications in an Older Man

Article

A 77-year-old man is brought to the emergency department after severaldays of illness that began with fever, nausea, emesis, and headache. Muscleweakness and associated myalgia developed; the weakness became so severethat the patient needed help to get out of bed and walk to the bathroom.The day before he came to the hospital, he slept much of the time and wasdifficult to arouse.

A 77-year-old man is brought to the emergency department after severaldays of illness that began with fever, nausea, emesis, and headache. Muscleweakness and associated myalgia developed; the weakness became so severethat the patient needed help to get out of bed and walk to the bathroom.The day before he came to the hospital, he slept much of the time and wasdifficult to arouse.

HISTORY
For several years, the patient has had mild diabetes, which is well controlledby glyburide, 10 mg/d. Last year, congestive heart failure was diagnosed;the ejection fraction at that time was 40%. Nonetheless, the patient, whois retired, has been active and able to care for himself. He recently returnedfrom a 2-week Labor Day vacation on Long Island, NY.

PHYSICAL EXAMINATION
The patient is lethargic. Temperature is 39oC (102.2oF); heart rate,110 beats per minute; and blood pressure, 105/75 mm Hg. Heart, lungs, andabdomen are normal, and neck is supple. There is no pallor or icterus of themucosae. Although the patient is able to move all extremities, his musclesare diffusely weak. There are no localized neurologic findings; however, he issomnolent and difficult to arouse.

LABORATORY RESULTS
White blood cell count is 12,000/μL with a normal differential. Serumsodium level is 131 mEq/L, and glucose level is 278 mg/dL. Lumbar punctureshows the cerebrospinal fluid (CSF) to have a protein level of 400 mg/dL, anormal glucose level, and a pleocytosis of 980 white blood cells/μL with 88%lymphocytes.

Which of the following is not true about the most likely diagnosis inthis patient?

A. Advanced age (greater than 70 years) is the risk factor most likely to bepredictive of death.
B. This patient will benefit from plasmapheresis for 7 days.
C. There is roughly a 50% probability that this patient will have long-termmorbidity as a result of this illness.
D. The most efficient method of diagnosis is detection of IgM antibody inthe patient's serum or CSF.

CORRECT ANSWER: B
This patient's presentation is typical of West Nile virus infection,which is well known in the Eastern hemisphere butwas not introduced into the United States until 1999. Thevirus's geographic distribution in this country has expandedrapidly; each summer more cases are reported. The virus isa flavivirus that contains a single-stranded RNA core and isrelated to the virus that causes St Louis encephalitis.

Epidemiologic clues. The epidemiology and ecologyof the West Nile virus have been well studied and described.1 Its primary enzootic cycle involves birds andmosquitoes. More than 20 species of North Americanmosquitoes have been shown to spread the virus; themost frequently affected birds are corvids (which includecrows and jays).When the mosquitopopulationescalates, the primaryenzooticcycle expands;the number of"bridge vector"mosquitoes(those that biteboth humansand birds) increasessufficientlyto causehuman outbreaksof the disease.

This patient'shistorycontains 2 strong epidemiologic clues to a diagnosis ofWest Nile virus infection. First, he had recently traveled toan area susceptible to mosquito infestation (Long Island,NY). Second, the timing of his trip coincided with the periodof peak incidence of West Nile virus infection in theUnited States (the last 2 weeks of August and the first 2weeks of September). The incubation period for the infectionis 2 to 14 days, which also fits well with the historyhere. The clinical presentation--an acute febrile illnesswith features of encephalitis and/or meningitis--is typicalas well.

Most West Nile virus infections are mild; thus, infectedpersons usually do not seek medical attention. Advancedage is the key risk factor for serious disease.Roughly 1 in 150 infections results in neurologic involvement;the risk of such involvement increases exponentiallywith age, beginning at age 50 years.2 In fact, it is prudentto seriously consider West Nile virus infection in anyolder adult in whom unexplained encephalitis or meningitisdevelops in late summer or early fall.3

CSF clues. The CSF findings here-pleocytosis withlymphocytic predominance, elevated protein, and normalglucose-are typical of West Nile virus infection. Thepleocytosis would be unusual in Guillain-Barr syndrome,which can be confused with West Nile in patients withprofound muscle weakness. Patients with Guillain-Barrésyndrome-but not those with West Nile virus infection-benefit from pheresis therapy. Treatment of West Nile,clearly the most likely diagnosis here, is supportive. Thus,choice B is not true.

CSF testing is an excellent method of establishingthe diagnosis of West Nile virus infection. A CSF enzymelinkedimmunosorbent assay (ELISA) that tests for IgMantibody is 95% sensitive.3 (A serum IgM ELISA is 90%sensitive.) This makes choice D true.

Prognosis. Once neurologic complications have developed,as in this man, fatality rates of 10% to 15% are therule.2 The most important risk factor for a fatal outcome isage greater than 70 years, so choice A is true. Other riskfactors include encephalitis with muscle weakness and alteredconsciousness.

Unfortunately, the prognosis for patients who surviveserious West Nile virus infection is guarded. Long-termmorbidity (in the form of residual fatigue, memory loss,and weakness with impaired ambulation) has been reportedin roughly 50% of survivors.4 Thus, choice C is alsotrue.

Outcome of this case. West Nile virus infection wasdiagnosed by CSF IgM ELISA. The patient survived theillness; however, 6 months later he still had persistentmuscle weakness and decreased mental acuity. He is ableto remain at home but needs significant help in caring forhimself.

References:

REFERENCES:1. West Nile virus activity-United States, 2001. MMWR. 2002;51:497-501.
2. Nash D, Mostashari F, Fine A, et al. The outbreak of West Nile virus infectionin the New York City area in 1999. N Engl J Med. 2001;344:1807-1814.
3. Petersen LR, Marfin AA. West Nile virus: a primer for the clinician. Ann InternMed. 2002;137:173-179.
4. Weiss D, Carr D, Kellachan J, et al. Clinical findings of West Nile virus infectionin hospitalized patients, New York and New Jersey, 2000. Emerg Infect Dis.2001;7:654-658.

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