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“UNDERUTILIZED” TEST MAY BE THE KEY TO MENINGITIS DIAGNOSIS
NEW YORK CITY—The clinical dilemmas in the diagnosis of meningitis are to differentiate bacterial from viral disease and to sort out the conditions that mimic acute bacterial meningitis, according to Burke A. Cunha, MD. Speaking at the Second Biennial New York Symposium on Neurologic Emergencies and Neurocritical Care, Dr. Cunha, Chief of the Infectious Diseases Division at Winthrop–University Hospital in Mineola, New York, said that the combination of cerebrospinal fluid (CSF) analysis and the clinical picture can usually provide a working diagnosis on which to base empiric antibiotic therapy.
The measurement of lactic acid in CSF is of particular value, said Dr. Cunha, who is also Professor of Medicine at the State University of New York School of Medicine at Stony Brook. “CSF lactic acid is an underappreciated and underutilized test that has been derided in the literature,” Dr. Cunha said, “but when used correctly it gives important diagnostic information that is available almost immediately.”
INITIAL CSF ASSESSMENT
The determination of lactic acid is “second in importance only to the Gram stain for differentiating between bacterial and viral meningitis,” Dr. Cunha explained. If the CSF lactic acid level is less than 3 mmol/L, the patient has aseptic meningitis or a parameningeal infection. CSF lactic acid levels greater than 10 mmol/L point to bacterial meningitis, and levels between 3 and 6 mmol/L are difficult to interpret but usually indicate partially treated meningitis.
Gram stains of CSF are positive in more than 90% of patients with bacterial meningitis, Dr. Cunha said, and meningitis is usually due to a single organism, so a mixed morphology suggests an alternate diagnosis (eg, brain abscess). The differential diagnosis when CSF is purulent but the Gram stain shows no organism, Dr. Cunha said, includes meningitis caused by Streptococcus pneumoniae or Neisseria meningitidis, “but if there are few white blood cells in the CSF the infection is probably pneumococcal.”
Gram-positive cocci, Dr. Cunha said, suggest S pneumoniae but may suggest Staphylococcus aureus septic emboli to the CNS in an intravenous drug user or a patient with endocarditis, or Staphylococcus epidermidis in a patient with an atrioventricular shunt. “Subacute bacterial endocarditis presents as aseptic meningitis,” he said, “but the meningitis is purulent in acute bacterial endocarditis.” The most important Gram-positive bacillus found in CSF is Listeria, which usually infects the elderly or patients with T-lymphocyte defects, Dr. Cunha said. The finding of Gram-negative cocci, however, implies N meningitidis (meningococcal disease) unless the CSF analysis reveals a polymicrobial process, while Gram-negative bacilli are most commonly due to Haemophilus influenzae.
Modest elevations in CSF protein levels, Dr. Cunha said, are not diagnostically useful. According to Dr. Cunha, when the CSF contains predominantly polymorphonuclear leukocytes and glucose is decreased, the differential diagnosis includes partially treated bacterial meningitis or meningitis caused by Listeria. “The CSF lactic acid measurement will identify partially treated meningitis,” he said, “and the Gram stain will reveal Listeria as a Gram-positive bacillus.”
RECOGNIZING MENINGOCOCCAL MENINGITIS
The salient clinical feature of meningococcal meningitis is the speed with which the illness appears and becomes critical. A crucial diagnostic clue, Dr. Cunha pointed out, is the timing of associated fever blisters. In herpes meningoencephalitis, herpes labialis typically precedes the neurologic syndrome by a week or more, he said. “Simultaneous meningitis and herpes labialis makes pneumococcal or meningococcal disease the likely diagnosis,” he added.
Prognosis in meningococcal meningitis is related to the number of petechial lesions, Dr. Cunha commented. “The greater the number of asymmetric extremity and truncal petechiae,” he said, “the less likely that the patient will survive.” He urged that antibiotic therapy be started immediately if the patient has irregular petechial lesions distributed all over the body, a purulent milky CSF, and Gram-negative diplococci in or around white blood cells in the CSF.
Dr. Cunha said that pneumococcal meningitis can also be associated with asymmetric extremity and truncal petechial lesions, and even fever blisters, especially in children and asplenic persons, but the Gram stain is rarely negative and the meningitis tends to follow community-acquired pneumococcal pneumonia. Other causes of petechial lesions include S aureus infection and Rocky Mountain spotted fever, which can mimic viral meningitis. “With S aureus the petechial lesions are more symmetric on the extremities and CSF lactic acid levels will be high, but in Rocky Mountain spotted fever the petechiae are distributed symmetrically about the wrists and ankles and the CSF chemistry profile resembles that of viral meningitis,” he noted.
ASEPTIC AND VIRAL MENINGITIS
In aseptic meningitis, Dr. Cunha said, defervescence is usually slow. In addition, CSF glucose levels usually are not decreased, as they are in bacterial meningitis. “There are three key exceptions, however,” he warned: “Herpes meningoencephalitis, lymphocytic choriomeningitis, and mumps meningitis.” CSF glucose is also decreased in fungal, tuberculous, and amebic meningitis and by the presence of red blood cells in the CSF.
According to Dr. Cunha, two viral forms of meningitis can mimic bacterial meningitis—enteroviral meningitis and herpes meningoencephalitis. “Enteroviral meningitis is a summer illness associated with a maculopapular rash, sore throat, and diarrhea, with a negative CSF Gram stain and a normal CSF lactic acid level,” he said.
Herpes meningoencephalitis results in a very different clinical and laboratory picture. “Herpes, the great imitator, is nonseasonal and often causes dense and prolonged cognitive and neurologic defects,” Dr. Cunha explained. Moreover, electroencephalographic studies, which reflect this disease earlier than imaging, reveal a unilateral temporal lobe focus. Like bacterial meningitis, however, and in contradistinction to most viral forms of meningitis, herpes meningoencephalitis is characterized by elevated polymorphonuclear leukocyte counts and red blood cells in CSF.
NOTEWORTHY MIMICS
According to Dr. Cunha, other mimics of acute bacterial meningitis include brain abscess with a ventricular leak, endocarditis, leptospirosis, lupus cerebritis, Lyme disease, meningeal carcinomatosis, meningeal sarcoid, and Mycoplasma meningoencephalitis. Most of these, he said, can be diagnosed on the basis of their non-neurologic manifestations. However, brain abscess “can be tricky,” he said. “The CSF profile resembles that of bacterial meningitis, except that the protein level is very highly elevated, and the number of white blood cells can exceed 100,000.”
Leptospirosis used to be rare, Dr. Cunha said, but is now seen increasingly in world travelers. “Leptospirosis is the only aseptic meningitis in which the CSF bilirubin level is higher than the peripheral bilirubin,” he pointed out. The clinical picture includes conjunctival suffusion, and the encephalopathic features may be enhanced by hepatic failure, if present.
The patient with Mycoplasma meningoencephalitis, Dr. Cunha added, will have “sky-high” cold agglutinin titers and a recent history of pharyngitis, otitis, or pneumonia. “Titers greater than 1:64 are diagnostic for mycoplasmal infection,” he said, “but in patients with meningitis titers are 1:1000 or more.”
The diagnosis of Rocky Mountain spotted fever is based on seasonal and exposure factors, but Dr. Cunha cited several clinical clues: “Patients have bilateral periorbital edema and extremity edema of the backs of the hands and feet. The only other diseases that cause these are toxic shock syndrome and Kawasaki disease, and they are not usually associated with encephalopathy.”
EMPIRIC THERAPY
Dr. Cunha emphasized the importance of using “meningeal doses” of antibiotics. “The drug has to be given in a high enough dose to ensure that the CSF concentration is adequate against the suspected neuropathogens,” he said. Currently, the combination of ceftriaxone and ampicillin is the empiric treatment of choice for bacterial meningitis, he stated. If culture fails to reveal Listeria, he added, the ampicillin can be discontinued after 24 hours. If Listeria is documented, however, the ceftriaxone is discontinued and ampicillin is given in “meningeal doses”—12 g/d for two weeks. Patients with herpes meningoencephalitis are treated with acyclovir.
The use of the CSF lactic acid, however, determines the need for empiric therapy for meningitis at Winthrop–University Hospital, Dr. Cunha reported. Standard therapy when meningitis was suspected had been to treat with ceftriaxone for 72 hours, he said. However, if the CSF lactic acid level is normal (which rules out a bacterial cause), ceftriaxone is not given, thus saving “significant expenses related to intravenous antibiotic use and hospitalization.”
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—Elliot Richman
Suggested Reading
1. Bailey EM, Domenico P, Cunha BA. Bacterial or viral meningitis? Postgrad Med. 1990;88:217-223.
2. Cunha BA. The diagnosis and therapy of acute bacterial meningitis. In: Schlossberg D, ed. Infections of the Nervous System. Clinical Topics in Infectious Disease. New York, Springer-Verlag, in press.
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