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1. General Introduction
It is helpful to distinguish meningitis from two other major categories of central nervous system (CNS) infection, namely, encephalitis and mass lesions (mainly brain abscess) because the most common causes of these syndromes are quite different. Meningitis may be caused by a variety of organisms (bacteria, viruses, fungi) whereas encephalitis is usually caused by viruses and brain abscess is usually caused by bacteria.
Meningitis (inflammation of the meninges) is characterized by fever, headache, stiff neck, sometimes photophobia, and an abnormal cerebrospinal fluid (CSF) examination. Encephalitis and mass lesions usually have features of cerebral disturbance such as somnolence, seizures, and focal findings (e.g. weakness of a limb). [Some aggressive forms of meningitis (e.g. tuberculous, pneumococcal) can cause vascular thromboses or even superficial cerebritis, mimicking to some extent encephalitis.]
Infection can occur in the CNS through four routes: hematogenous spread, contiguous spread (e.g. from paranasal sinuses, middle ear), direct inoculation (after surgery or accidental trauma) and, for a few agents, by retrograde spread up nerves (HSV, rabies).
Most cases of bacterial meningitis begin with infection in the nasopharynx (which may be only minimally symptomatic). The infection spreads either by the hematogenous route or directly through the pharyngeal epithelium into the CNS. Encapsulated organisms (see slide) are prime offenders because, in the absence of specific antibody, their capsules protect them against phagocytic defenses.
3. Clinical Features
Inflammation of the meninges causes fever, headache, and sometimes photophobia. There is usually nuchal rigidity though this may be minimal or absent in the very young or old and in patients with HIV infection. There is often an antecedent prodrome (fever, aching, perhaps sore throat). The CSF is almost always abnormal.
The pattern of CSF abnormality (the “CSF profile”) together with the pace (rapidity of onset) of the disease, certain clinical clues (age of the patient, presence of immunosuppression, presence of cranial nerve palsies), allow the physician to develop a likely diagnosis. In the case of bacterial meningitis, the common causes differ markedly according to the age and immune status of the patient (see slide titled Risk Groups). Infection by Hemophilus influenzae, which used to be the most common cause of bacterial meningitis in young children, has nearly disappeared as a result of the vaccine.
Three CSF profiles are common (see slide titled CSF "Profiles"): (a) purulent – with abundant pleocytosis, mainly PMNs, and a low glucose (often less than 20 mg/dl), usually caused by bacteria and usually featuring an abrupt onset; (b) lymphocytic low glucose – with fewer than 500 cells/mm3 of CSF, mainly lymphocytes, a moderately low (and falling) glucose, a subacute onset, and, often, cranial nerve palsies, caused by a variety of treatable infections as well as some noninfectious conditions; and (c) lymphocytic normal glucose – with a modest lymphocytic pleocytosis and a normal glucose level, caused mainly by enteroviruses.
It should be noted that these CSF profiles evolve over hours and days and, especially in the case of the lymphocytic low glucose profile, repeated taps may be needed to detect a significantly falling glucose level. As bacterial meningitis is treated, the CSF profile moves from purulent to lymphocytic low glucose to lymphocytic normal glucose. Listeria infection, though grouped with purulent infections, may have a subacute onset and lymphocytic pleocytosis. West Nile Virus infection can produce a meningitis, encephalitis, or a poliovirus like illness (destruction of anterior horn cells).
The diagnosis of meningitis is made by the clinical picture and CSF profile. The identification of the cause is made by gram-stain and culture (for bacteria), viral culture and possibly PCR for viruses. Perhaps the single most important category to be aware of is the lymphocytic low glucose profile: early on, it can be mistaken for the lymphocytic normal glucose profile, attributed to viral infection and not treated. Infections which may be fatal if not treated can thereby be overlooked – including tuberculous, fungal (cryptococcus, histoplasma, coccidioides), and spirochetal (Lyme, syphilis) infections. (See slide for some methods of diagnosis of these infections.) Of the causes of lymphocytic low glucose meningitis, the most difficult to diagnose is tuberculosis. Often, it must be treated empirically (while awaiting culture results) after other causes have been ruled out.
For initial empiric treatment in children and adults, a cephalosporin is recommended (aimed at the meningococcus and the small possibility of Staphylococcus aureus, Hemophilus influenzae or a gram-negative enteric organism) together with vancomycin (to cover for penicillin-resistant pneumococci). Based on the results of a recent study, it is recommended that dexamethasone be started at the same time as antibiotic treatment is begun in order to quell the inflammatory reaction and produce a better outcome. Once the results of cultures and sensitivity testing are available, this regimen can be modified.
6. Ancillary Material
- de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002;347(20):1549-56.
- Hasbun R, Abrahams J, Jekel J, Quagliarello VJ. Computed tomography of the head before lumbar puncture in adults with suspected meningitis. N Engl J Med 2001;345(24):1727-33.
- Quagliarello VJ, Scheld WM. Treatment of bacterial meningitis. N Engl J Med 1997;336(10):708-16.
- Saez-Llorens X, McCracken GH, Jr. Bacterial meningitis in children. Lancet 2003;361(9375):2139-48.
- Schuchat A, Robinson K, Wenger JD, et al. Bacterial meningitis in the United States in 1995. Active Surveillance Team. N Engl J Med 1997;337(14):970-6.