Aseptic Meningitis: A Seasonal Concern
by James L. Moeller, MD
THE PHYSICIAN AND SPORTSMEDICINE - VOL 25 - NO. 7 - JULY 97
In Brief: Outbreaks of aseptic meningitis-like illnesses have occurred in high school football players for reasons that may include the close contact among players and the overlap of football season with the peak enterovirus season. The main symptoms are fever, headache, and neck or back stiffness; physical findings may include signs of meningeal irritation. Evaluation of the cerebrospinal fluid can confirm the diagnosis. Treatment of viral meningitis is generally supportive, and patients usually do well, while other forms of aseptic meningitis may require drug treatment or removal of inciting medications. Not sharing water bottles may help reduce risk.
Aseptic meningitis is a relatively uncommon, but not rare, syndrome that is usually seen in the enterovirus season—July, August, and September (1). Populations that appear to be more susceptible to aseptic meningitis, particularly viral meningitis, include children and elderly persons who interact or live in group settings. High school football players may also be at increased risk, perhaps because of the timing of football season and sharing of water bottles (2,3). Thus physicians should be alert to this possibility if players present with meningitis-like symptoms. Because of the ominous prognosis of bacterial meningitis, prompt and accurate diagnosis of meningitis in any form is necessary so that proper treatment can be initiated.
There are many causes of aseptic meningitis (table 1: not shown). "Viral" and "aseptic" are often used interchangeably when referring to meningitis, even though "aseptic" simply means "nonbacterial." Although several different pathogens, including Mycobacterium tuberculosis and various fungi, can cause aseptic meningitis, most cases are viral. Enteroviruses cause over half of the confirmed cases of viral meningitis (1,4,5). Viral meningitis can occur at any age, but usually occurs in people under the age of 40 (1,4), with those aged 5 to 15 most commonly affected (2).
The types of enteroviruses causing viral meningitis vary annually. Transmission is primarily fecal-oral with infection occurring across mucous membranes (1,5). After the virus has replicated within the gastrointestinal tract (1), viremia is established, followed by viral crossover at the blood-brain barrier into the subarachnoid space (1,5). Alterations in the blood-brain barrier then allow white blood cells (WBCs) and other inflammatory components into the cerebrospinal fluid (CSF) (5).
Most patients show some obvious signs and symptoms of meningitis. Fever, headache, vomiting (1,4,5), neck or back stiffness, photophobia (1,5), and mental states ranging from lethargy (1,4) to coma are often present.
The onset of symptoms may be acute (less than 24 hours) or subacute (occurring over 1 to 7 days). When a patient presents with acute meningitis, immediate treatment is the first consideration (1). A more specific diagnosis can be pursued after treatment has begun.
A subacute onset of symptoms usually causes physicians to consider a nonbacterial etiology. All types of meningitis, however, may develop acutely or subacutely, with most cases developing subacutely. In fact, up to 75% of patients who have bacterial meningitis have a subacute onset (1). The remainder of this article focuses on the subacute presentation.
Important elements of the history include the patient's age (5), the time of year (1,5), exposure to vectors such as mosquitoes and ticks, medications taken currently or recently, systemic illnesses, exposure to tuberculosis, travel out of the country, human immunodeficiency virus (HIV) risk factors, and history of meningitis (5). Inquiry should also be made about recent contact with anyone who had an acute illness, especially meningitis.
On physical examination, a patient who has meningitis is generally febrile and uncomfortable (5). Mental status is usually normal, but varying degrees of abnormal mental status may be present (1). A full neurologic examination should be performed whenever meningitis is suspected. Impaired sensorium or focal neurologic findings should raise suspicion of encephalitis or a space-occupying lesion such as a brain abscess (5). Fundoscopic examination for papilledema is important. Papilledema is very rare in meningitis, and its presence should raise the suspicion of a mass lesion. The possibility of an abscess should be considered when findings such as otitis media or sinusitis are present (5).
Signs of meningeal irritation should also be sought whenever meningitis is suspected. Kernig's sign and Brudzinski's sign are common with meningeal irritation (4,5). Kernig's sign is positive if resistance to passive leg extension occurs when the patient is seated or when the hip is flexed. Brudzinski's sign is positive if involuntary flexion of the hips occurs when the supine patient's neck is passively flexed abruptly.
Some other physical findings may increase suspicion of particular etiologic agents: Parotitis is associated with mumps, herpangina with Coxsackie virus, and herpetic lesions with herpesvirus (3).
Lab Tests Hold the Key
It is virtually impossible to distinguish between bacterial and aseptic meningitis with clinical findings alone (6). The most important laboratory test for diagnosing meningitis—and the most useful tool for distinquishing between aseptic and bacterial forms—is prompt CSF analysis. The CSF should be studied for cell count and differentials, glucose levels (as compared with a simultaneous serum glucose), lactate, and protein levels. Various cultures, stains, and assays are also important, depending on the setting.
CSF cell count. In patients who have aseptic meningitis, the CSF cell count is usually less than 1,200 per mm3 (5). Mononuclear cells are usually predominant in these patients, but polymorphonuclear (PMN) cells may predominate early in the course of the disease (5,6,8). Bacterial meningitis, like aseptic meningitis in early stages, causes pleocytosis (usually greater than 1,000 per mm3 (1,6), along with a predominance of PMNs (6). Because of similarities between CSF results in aseptic and bacterial meningitis, many feel that, with a subacute presentation in an otherwise stable patient, repeat evaluation of the CSF to look for a shift from PMNs to mononuclear cells is warranted prior to antibiotic therapy (5,6,8). The total cell count is usually, but not always, higher in bacterial meningitis.
CSF protein. CSF protein elevations are common with both bacterial and aseptic meningitis. Meningitis caused by viral agents often produces a smaller increase in CSF protein levels, but as with cell counts, frequent similarities between protein levels in aseptic and bacterial meningitis raise doubts about the usefulness of CSF protein counts in distinquishing meningitis types (5).
CSF glucose. CSF glucose levels should be compared with simultaneous serum glucose levels. A ratio of CSF glucose to serum glucose of approximately 66% is considered normal (5,6). In patients who have aseptic meningitis, CSF serum glucose ratios are usually within the normal range, (5) whereas bacterial meningitis causes a decrease in CSF glucose (1,6,8). However, as with cell counts, differentials, and protein measurements, the ranges of glucose values for the two types overlap considerably.
It is difficult to diagnose bacterial vs aseptic meningitis on the grounds of CSF cell count, differential, protein, and glucose evaluations alone. Test results in 30% to 40% of patients who have nontuberculous bacterial meningitis will fall in the range of values typical of tuberculous, fungal, and viral meningitis (1).
CSF lactate. Tests for CSF lactate and serum C-reactive protein (CRP) concentrations may be helpful for distinguishing between bacterial and viral meningitis. CSF lactate levels of greater than 6 mmol/L indicate bacterial meningitis, in contrast to lactate levels in viral meningitis of less than 3 mmol/L (17). Bacterial meningitis will cause a CRP level higher than 20 mg/L (18).
Cultures and stains. Cultures of the CSF are extremely helpful for determining specific bacterial causes of meningitis, and may be the only laboratory results that clearly differentiate bacterial from viral meningitis. Bacterial cultures should always be performed (1,5), and culturing for fungi and staining for AFB should be considered (5). Other tests for M tuberculosis, such as high-performance liquid chromatography, which uses fluorescence for detection of mycolic acids (9-11), or polymerase chain reaction (PCR) assays (12,13), may assist rapid diagnosis in cases of tuberculous meningitis. Gram's staining is helpful if bacteria are present. India ink studies to look for cryptococcus may also need to be obtained. Viral cultures may be of use but are very difficult; the isolation rate of enteroviruses ranges from 43% to 77%, depending on the serotype (19). Viral serology is not helpful in the acute setting as obtaining acute and convalescent sera takes 3 weeks (5), but it may be helpful in making a final diagnosis of viral vs other forms of aseptic meningitis. PCR can enable rapid detection of herpes simplex virus (HSV) in the CSF (14,15). Rapid HSV detection is important because, although infection with HSV-2 is usually self limited, HSV-1 infections may cause a rapidly progressing, fatal encephalitis (16).
WBC counts. Peripheral WBC counts have not been shown to be helpful in distinguishing bacterial from aseptic meningitis (5,6). In either form, the WBC count can be normal, slightly elevated, or greatly elevated. The differential of the peripheral WBC count has not proven to be of benefit either (6).
The most important step in treating subacute aseptic meningitis is a fast and accurate diagnosis. Treatment for patients who have viral meningitis is generally supportive, and the course is usually benign (5). Intravenous hydration and antipyretics may be required.
In some patients, other medications may be used. Certain types of viruses should be treated with antiviral agents, but this is usually when encephalitis is present. With HSV infection, acyclovir is the treatment of choice. When meningitis is caused by M tuberculosis, isoniazid and rifampin are the major components of therapy (16).
When the diagnosis is uncertain, antibiotics can be started while cultures are pending (1). Antibiotic choices are generally based on the age of the patient as well as pathogens common to the hospital or region. If a bacterial cause is ruled out, antibiotics may be withdrawn. Currently, however, many feel that for patients who present subacutely, evaluation of the CSF should be repeated 6 to 24 hours after the initial examination and before starting antibiotics—particularly when CSF findings are indeterminate and Gram's stain is negative (5,6,8).
A Football Connection?
There have been multiple reports of aseptic meningitis-like illnesses in high school football players. Between 1978 and 1980, seven outbreaks in four states were reported (2,3).
For several reasons, high school football players may be at greater risk of aseptic meningitis. Factors that may increase the risk are the concurrence of football practice and games with peak enterovirus season, frequent physical contact among football players, sharing of water bottles, and the greater physical exertion among football players as compared with participants in other sports. The latter factor may predispose these athletes to aseptic meningitis where other athletes exposed to the same enterovirus might have a milder clinical illness (2). Other team sports are played in the enterovirus season and present similar aseptic meningitis risk factors, but there have been no reports of outbreaks among these players. Perhaps the amount of head contact in football increases the risk.
Changes in CSF cell count and biochemistry consistent with aseptic meningitis have been noted following brain and spinal cord injury (20,21). It is hypothesized that these injuries may cause bleeding into the CSF coupled with an inflammatory response, resulting in increased WBC count (20,21). A study of patients who had spinal cord injuries showed a corrected WBC count of 48.9 per mm3 in patients whose lumbar punctures were performed within 7 days of injury. The majority of the cells were PMNs (57.8%), followed by lymphocytes (23.4%), and finally monocytes (19.6%). Elevated CSF protein was also found (mean elevation 125 mg/dL) (21). The patients in these studies (20,21) were all victims of non-sports-related trauma. The similarities, however, may lead to the question: Does head trauma from football or other collision sports alter CSF cell count and biochemistry, potentially mimicking aseptic meningitis in laboratory tests? The available evidence leaves this question unanswered.
Aseptic meningitis has also been shown to result from exposure to certain medications (4,5,7,22) and other chemicals (1,7). Chemical-induced aseptic meningitis generally occurs because of direct contact of the irritant with the meninges. Substances that may cause this entity include radiologic contrast dyes, chemotherapeutic agents (1,7) various other drugs, detergents, preservatives, and even talc (table 2: not shown) (7).
Aseptic meningitis induced by nonsteroidal anti-inflammatory drugs (NSAIDs) appears to be a hypersensitivity reaction (4,7,22) and is most commonly seen in patients who have concomitant diseases such as systemic lupus erythematosus (7,22) or connective tissue disease (7). Ibuprofen in particular is one of the more common causes of drug-induced aseptic meningitis (4,7,22). Because many people use over-the-counter ibuprofen for headaches and the aches and pains associated with physical activity, the true etiology of aseptic meningitis in some patients may be difficult to discover.
Drug-induced aseptic meningitis is a diagnosis of exclusion (4,7,22). Discontinuation of the offending drug usually leads to resolution of symptoms in less than 48 hours (4,22).
Precautions for Prevention
Because the reasons for athletes' possibly increased risk of aseptic meningitis are speculative, it is difficult to suggest how to reduce the risk, but eliminating sharing of common drinking water and ice sources such as hoses, water bottles, and team coolers may be of some benefit. In addition, hand washing is good for prevention of many illnesses including aseptic meningitis, conjunctivitis, flu, and gastroenteritis.
Dr Moeller is associate director of primary care sports medicine and an assistant professor in the departments of family medicine and orthopedic surgery at the University of Pittsburgh Medical Center in Pittsburgh. He is a member of the American College of Sports Medicine and the American Medical Society for Sports Medicine. Address correspondence to James L. Moeller, MD, Director, Primary Care Sports Medicine, University Orthopaedics, Inc, 3471 Fifth Ave, Kaufman Bldg, Ste 1000, Pittsburgh, PA 15213; e-mail to [email protected].
Copyright (C) 1997. The McGraw-Hill Companies. All Rights Reserved