Aseptic Meningitis

December 31, 2006

A 23-year-old man presents to the emergency department with fever, headache,and photophobia. His illness began 5 days earlier with malaise, followed byfever, prostration, nausea, and vomiting. After 3 days, a severe headache developed,accompanied by photophobia; the headache did not respond to over-thecounteranalgesics.

Case 1

Young Man With Fever, SevereHeadache, and Photophobia

A 23-year-old man presents to the emergency department with fever, headache,and photophobia. His illness began 5 days earlier with malaise, followed byfever, prostration, nausea, and vomiting. After 3 days, a severe headache developed,accompanied by photophobia; the headache did not respond to over-thecounteranalgesics.

HISTORY

The patient was previously healthy, and he takes no long-term medications.To his knowledge, he has not been exposed to anyone with a contagiousdisease. However, he has casual contact with many people in the course of hiswork: he is a subway conductor, and the trains have been crowded lately becauseit is the winter holiday season.

PHYSICAL EXAMINATION

Temperature is 39.4C (103F); heart rate, 92 beats per minute; respirationrate, 12 breaths per minute; and blood pressure, 110/70 mm Hg. Mucosae aredry, and the eyes are injected. Lymph nodes are not enlarged. Lungs and heartare normal. Bowel sounds are diminished, but the abdomen is soft, nontender,and without masses. No rash is present. A neurologic examination reveals slightnuchal rigidity but no focal or lateralized findings. Mentation is normal.

LABORATORY RESULTS

LABORATORY RESULTSHemoglobin level is 14.2 g/dL, white blood cell (WBC) count is 5300/?L(59% granulocytes and 41% lymphocytes), and platelet count is 159,000/?L.Creatinine level is 1.2 mg/dL, blood urea nitrogen level is 5 mg/dL, and electrolytelevels are normal with no anion gap. Transaminase levels are normal.Blood glucose level is 84 mg/dL. Analysis of cerebrospinal fluid (CSF) revealsa WBC count of 452/?L (5% segmented forms, 95% lymphocytes); glucoselevel, 70 mg/dL; and protein level, 89 mg/dL. A CSF specimen is sent for microbiologicevaluation; results are pending.

Which of the following is the most likely cause of this patient's illness?

A.

Streptococcus pneumoniae.

B.

West Nile virus.

C.

Neisseria meningitidis.

D.

An enterovirus.

Case 1:

CORRECT ANSWER: D

Because this patient has a febrile illness with severe headache,photophobia, and slight nuchal rigidity, meningitis figuresprominently in the differential diagnosis. All 4 organismslisted are associated with meningitis. The CSF findingsand the epidemiologic features of the case will beparticularly helpful in identifying the causative organism.The pleocytosis of less than 500/μL with a predominantlymphocytosis, normal CSF glucose level, and elevatedCSF protein level are typical of viral, or aseptic, meningitis.On occasion, a lymphocytic predominance is seen inbacterial meningitis very early in the disease; however, ahigher total WBC count with a marked polymorphonuclearpredominance and a concomitant decrease in theCSF glucose level are more typical findings.When meningitis is suspected, Gram staining of aCSF sample can demonstrate the gram-negative diplococciof

N meningitidis

or the gram-positive cocci of pneumococcaldisease. However, the timing of this patient's CSF examination(roughly 5 days since symptom onset) and thenature of the findings make both

N meningitidis

(choice C)and

S pneumoniae

(choice A) unlikely causes of his illness.Nonetheless, many clinicians who have deemed an illnessserious enough to perform lumbar puncture will initiateempiric broad-spectrum antimicrobial therapy pending theresults of CSF culture.

1

This patient was given parenteralceftriaxone pending culture results.West Nile virus infection (choice B) is a newly emerginginfectious disease in the United States. It is caused by aflavivirus and involves an enzootic cycle with mosquito andbird vectors (crows are especially common). Its incidenceand geographic range are growing yearly. The West Nilevirus causes a mild illness that does not require medical attentionin most persons. Aseptic meningitis occurs in about1% of those infected, and a serious, life-threatening meningoencephalitisin still fewer--although the latter presentationis significantly more common in the elderly.

2

The clinicaland CSF findings seen here would not be inconsistentwith West Nile virus infection. However, this patient'sillness developed in the winter, and in the United States,West Nile virus infection has been a late summer phenomenon.Thus, the patient's age and the time of year makesevere West Nile virus infection unlikely here.The most likely diagnosis is

aseptic meningitis

, a relativelycommon condition in the United States. Although itis most often seen in children, aseptic meningitis affects allage groups. There is a 3:1 male predominance. In about15% of patients, the causative virus is identifiable--usuallyvia polymerase chain reaction (PCR) screening, which hasbecome the key diagnostic tool for most viral pathogens.The most common causative agents are the enteroviruses(choice D)--small nonenveloped RNA viruses that areusually spread by the hand-to-mouth route. Enteroviruses(which include polioviruses, coxsackieviruses, and echoviruses)account for 50% to 80% of aseptic meningitis caseswith an identifiable pathogen.

3

Other, less common causesof aseptic meningitis are arboviruses, HIV-1, and mumpsvirus. Epstein-Barr virus, cytomegalovirus, and influenzavirus are only rarely associated with an aseptic meningitissyndrome.Typical findings in patients with aseptic meningitis aresimilar to those seen here: headache, fever, stiff neck,malaise, nausea and vomiting, and photophobia. Focal signsand mental obtundation are rare and suggest another diagnosis.The prognosis is good; almost all patients recover in5 to 14 days with supportive care that consists of fluids andanalgesics. Rarely, severe illness with complications thateventually lead to death--such as pulmonary edema andhemorrhage and myocarditis--occurs. Such severe casesare most commonly seen in children younger than 5 years(the majority of deaths from aseptic meningitis occur in thisage group).

4

Outcome of this case.

Gram staining of a CSF samplewas negative for organisms, and after 24 hours the culturedspecimen displayed no growth. These results definitivelyexcluded bacterial meningitis. Parenteral ceftriaxonewas then stopped, and the patient was treated with fluidsand analgesics. He slowly improved and was dischargedon day 5. Subsequently, CSF PCR studies were positivefor enterovirus.

References:

REFERENCES:

1.

Quagliarello VJ, Scheld WM. Treatment of bacterial meningitis.

N Engl J Med.

1997;336:708-716.

2.

Peterson LR, Marfin AA. West Nile virus: a primer for the clinician.

Ann InternMed.

2002;137:173-179.

3.

Dolin R. Enterovirus 71-emerging infections and emerging questions.

N EnglJ Med.

1999;341:984-985.

4.

Ho M, Chen ER, Hsu KH, et al, for the Taiwan Enterovirus Epidemic WorkingGroup. An epidemic of enterovirus 71 infection in Taiwan.

N Engl J Med.

1999;341:929-935.