Acute Meningitis

Allan R. Tunkel, Diederik van de Beek, W. Michael Scheld

Keywords

adjunctive corticosteroids; bacterial meningitis; central nervous system infections; cerebrospinal fluid; chemoprophylaxis; conjugate vaccines; eosinophilic meningitis; meningitis; spirochetal meningitis; viral meningitis

Meningitis, or inflammation of the meninges, is identified by an abnormal number of white blood cells in cerebrospinal fluid (CSF). Acute meningitis is clinically defined as a syndrome characterized by the onset of meningeal symptoms over the course of hours to up to several days. Headache is a prominent early symptom, often followed later by a state of abnormal consciousness, or coma. Examination reveals few focal findings early during infection, although signs of meningeal irritation are common. The acute meningitis syndrome blurs imperceptibly into the syndromes of chronic meningitis (see Chapter 86) and encephalitis (see Chapter 87). Chronic meningitis has an onset measured in weeks to months (but is generally defined when symptoms, signs, and the CSF remain abnormal for at least 4 weeks), whereas encephalitis is distinguished by the presence of decreased mentation (i.e., abnormal state of consciousness, with or without seizures) early in the course of disease with minimal meningeal signs. The distinction between these syndromes is clinically useful in guiding management but is clearly artificial in terms of etiology and pathology. For example, tuberculous meningitis may have a subacute or a chronic onset.

The acute meningitis syndrome may be caused by a wide variety of infectious agents and may also be a manifestation of noninfectious diseases (Table 89-1). Diseases in which meningeal symptoms occur but are not predominant are excluded from the table. Many of the causes of chronic meningitis, which can be manifested acutely, have been omitted but are listed in Chapter 86. Here, we review the common infectious causes of acute meningitis, with particular emphasis on epidemiology and etiology, pathogenesis and pathophysiology, clinical manifestations, diagnosis, management, and prevention.

TABLE 89-1

Differential Diagnosis of Acute Meningitis

Major Infectious Causes

Viruses

Nonpolio enteroviruses ^a

Arboviruses^b

Herpesviruses^c

Lymphocytic choriomeningitis virus

Human immunodeficiency virus

Adenovirus

Parainfluenza virus types 2 and 3

Rickettsiae

Rickettsia rickettsii

Rickettsia conorii

Rickettsia prowazekii

Rickettsia typhi

Orientia tsutsugamushi

Ehrlichia and Anaplasma spp.

Bacteria

Haemophilus influenzae

Neisseria meningitidis

Streptococcus pneumoniae

Listeria monocytogenes

Escherichia coli

Streptococcus agalactiae

Propionibacterium acnes

Staphylococcus aureus

Staphylococcus epidermidis

Enterococcus spp.

Klebsiella pneumoniae

Pseudomonas aeruginosa

Salmonella spp.

Acinetobacter spp.

Viridans streptococci (e.g., S. salivarius)
Streptococcus gallolyticus

Fusobacterium necrophorum

Stenotrophomonas maltophilia

Streptococcus pyogenes

Streptococcus suis

Pasteurella multocida

Capnocytophaga canimorsus

Nocardia spp.

Mycobacterium tuberculosis

Spirochetes

Treponema pallidum (syphilis)

Borrelia burgdorferi (Lyme disease)
Borrelia miyamotoi

Leptospira spp.

Protozoa and Helminths

Naegleria fowleri

Angiostrongylus cantonensis

Baylisascaris procyonis

Taenia solium

Toxocara spp.

Strongyloides stercoralis (hyperinfection syndrome)

Other Infectious Syndromes

Parameningeal foci of infection^d

Infective endocarditis

Viral postinfectious syndromes

Postvaccination^e

Noninfectious Causes and Diseases of Unknown Etiology

Intracranial Tumors and Cysts

Craniopharyngioma

Dermoid/epidermoid cyst

Teratoma

Medications

Antimicrobial agents^f

Nonsteroidal anti-inflammatory agents^g

Muromonab-CD3 (OKT3)

Azathioprine

Cytarabine (high dose)

Carbamazepine^h

Immune globulin

Ranitidine

Phenazopyridine

Systemic Illnesses

Systemic lupus erythematosus
Behçet’s disease
Sarcoidosis

Vogt-Koyanagi-Harada syndrome

Procedure-Related

After neurosurgery

Spinal anesthesia

Intrathecal injectionsⁱ

Chymopapain injection

Miscellaneous

Seizures

Migraine or migraine-like syndromes

^a Primarily echoviruses and coxsackieviruses.

^b In the United States, the major etiologic agents are the mosquito-borne California, St. Louis, Eastern equine, and West Nile viruses and the tick-borne Colorado tick fever.

^c Primarily herpes simplex virus type 2 but also herpes simplex virus type 1, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6.

^d Brain abscess, sinusitis, otitis, mastoiditis, subdural empyema, epidural abscess, venous sinus thrombophlebitis, pituitary abscess, cranial osteomyelitis.

^e Mumps, measles, polio, pertussis, rabies, vaccinia.

^f Trimethoprim, sulfamethoxazole, trimethoprim-sulfamethoxazole, ciprofloxacin, penicillin, isoniazid, metronidazole, cephalosporins, pyrazinamide.

^g Ibuprofen, sulindac, naproxen, tolmetin, diclofenac, ketoprofen.

^h In patients with connective tissue diseases.

ⁱ Air, isotopes, antimicrobial agents, antineoplastic agents, corticosteroids, radiographic contrast media.

Epidemiology and Etiology

Viral Meningitis

Viruses are the major cause of the aseptic meningitis syndrome, a term used to define any meningitis (infectious or noninfectious), particularly one with a lymphocytic pleocytosis, for which a cause is not apparent after initial evaluation and routine stains and cultures of CSF.¹^,² Common viral etiologic agents that cause the acute aseptic meningitis syndrome are discussed in the following paragraphs.

Enteroviruses

Enteroviruses, currently the leading recognizable cause of aseptic meningitis syndrome, account for 85% to 95% of all cases in which a pathogen is identified.¹^,² Estimates from the Centers for Disease Control and Prevention (CDC) indicate that 10 to 15 million symptomatic enteroviral infections occur annually in the United States, which includes 30,000 to 75,000 cases of meningitis.³ However, these figures are most likely an underestimation of the true incidence because of underreporting of enteroviral cases from state laboratories to the CDC. Enteroviruses are worldwide in distribution. In temperate climates they appear with a marked summer/fall seasonality, although in tropical and subtropical areas a high year-round incidence is observed. Periods of warm weather and wearing sparse clothing may facilitate the fecal-oral spread of these organisms; enteroviruses have also been recovered from houseflies, wastewater, and sewage²; and disease has been reported after swimming in sewage-contaminated seawater.⁴ Approximately 100 serotypes of nonpolio enteroviruses have been recognized; in the United States, the 14 most commonly occurring enteroviral serotypes account for more than 80% of isolates.³^,⁵ From 2006-2008, based on data from two laboratory-based surveillance systems (the National Enterovirus Surveillance System and the National Respiratory and Enteric Virus Surveillance System), about 70% of cases occurred during July to October and the five most common were coxsackievirus B1, echovirus 6, echovirus 5, echovirus 18, and coxsackievirus A9, accounting for 54% of total serotyped detections.⁶ In addition, enteroviruses 70 and 71 have been reported to commonly cause central nervous system (CNS) disease.⁷^–¹⁰ Outbreaks of enteroviral meningitis have also been reported. One outbreak involved 29 travelers in a school-organized trip to Mexico¹¹; most cases were caused by echovirus 30 and coxsackievirus A1. From 2005 to 2008, enterovirus 71 was detected in 29 patients in Denmark,¹² with meningitis the most common diagnosis; other reported enteroviral meningitis outbreaks have been caused by coxsackievirus B3¹³ and echovirus 18.¹⁴^,¹⁵ Some enteroviral serotypes (namely, echoviruses 22 and 23) have been reclassified into the newly assigned genus Parechovirus; human parechovirus type 3 has been associated with severe disease and reported to cause viral meningitis.¹⁶

Infants and young children are the primary victims of enteroviral meningitis because they are the most susceptible host population (i.e., they are without previous exposure and immunity) within the community. More than one episode of enteroviral meningitis may develop, although the same enteroviral serotype has not been implicated more than once in any immunocompetent patient.² Enteroviruses are also the most common causes of aseptic meningitis in adults.¹⁷^,¹⁸ Immunodeficiency (specifically congenital or acquired impaired humoral immunity) and possibly physical exercise may predispose to enteroviral meningitis.²^,⁵ Cases of enteroviral meningoencephalitis have also been seen in patients treated with the chimeric anti-CD20 monoclonal antibody rituximab.¹⁹^,²⁰

Mumps Virus

In an unimmunized population, mumps is one of the most common causes of aseptic meningitis and encephalitis; symptomatic meningitis is estimated to occur in 10% to 30% of mumps patients overall,²¹ although in a recent outbreak of 2597 cases of mumps in the United States only 11 cases of meningitis were reported.²² In another outbreak of mumps orchitis from 2000 to 2001 in 67 patients in Gran Canaria Island, 9 patients had clinical and biochemical evidence of mumps meningitis.²³ CNS disease caused by mumps virus can occur in patients without evidence of parotitis,²^,²¹ and 40% to 50% of patients with mumps meningitis have no evidence of salivary gland enlargement. Meningitis is the most common neurologic manifestation of infection with mumps virus²^,²¹ and is usually a benign and self-limited process. Males are affected two to five times more often than females, and the peak incidence is in children aged 5 to 9 years. Cases of vaccine-associated mumps meningitis have also been reported.