Final Diagnosis -- Acute Pneumococcal Meningo-encephalitis



Streptococcus pneumoniae is the major cause of otitis media, sinusitis, meningitis and community-acquired bacterial pneumonia, as well as an infrequent cause of peritonitis, pelvic infections in women, septic arthritis, osteomyelitis, soft tissue infections and purulent endo- and pericarditis. Particularly severe or unusual pneumococcal infections can be seen in HIV-positive patients. 1, 2

The major host protection mechanism against pneumococcal infections is opsonophagocytosis. One of the most important virulence factors of S. pneumoniae is the presence of a polysaccharide capsule, which allows it to escape phagocytosis. However, anti-capsular antibodies acquired by exposure to the organism, or by vaccination, are effective in conferring protection against pneumococcal infections. The currently available pneumococcal vaccine incorporates 23 of the most pathogenic of the 80+ antigenically distinct capsular types that have been identified. 1, 2, 3

Other important pneumococcal virulence factors include: the teichoic acid and peptidoglycan constituents of the bacterial cell wall, surface proteins, pneumolysin (a cytoplasmic toxin released by autolysis of the cell) and, possibly, hyaluronidase (a glycosidase that degrades components of the extra-cellular matrix). 2, 3, 4

A number of conditions predispose to pneumococcal infections, including: defective antibody formation (congenital or secondary to conditions such as chronic lymphocytic leukemia, lymphoma or HIV infection); complement deficiency or dysfunction; neutropenia or neutrophilic dysfunction; splenectomy or splenic dysfunction; prior respiratory infections and inflammatory conditions such as cigarette smoking, asthma and COPD (chronic obstructive pulmonary disease). Multifactorial conditions, such as diabetes mellitus, renal insufficiency, liver cirrhosis, malnutrition, glucocorticosteroid therapy, alcoholism, cold exposure, stress, fatigue and excess likelihood of exposure to S. pneumoniae (such as occurs in daycare centers, college dormitories and military training camps), also contribute to host susceptibility to pneumococcal infection. 1, 2 Some factors that increase the risk of pneumococcal meningitis in particular are: chronic otitis media, head trauma with basilar skull fracture and cerebrospinal fluid (CSF) rhinorrhea. 5, 6

Bacterial meningitis is a severe, acute purulent infection of the leptomeninges and subarachnoid space. Extension of the inflammatory reaction into the brain parenchyma (meningoencephalitis) can result in increased intracranial pressure, seizures, stroke, coma and death. The mortality rate of bacterial meningitis can reach 25%, while adverse neurological outcomes are seen in upwards of 50% of survivors. 1, 4

Wide-spread use of the Haemophilus influenza type b vaccine, and the emergence and increasing prevalence of penicillin and cephalosporin-resistant strains of S. pneumoniae, have lead to changes in the epidemiologic profile of bacterial meningitis in the United States. Streptococcus pneumoniae is now the major cause of this disease, particularly in adults, accounting for around 15% of total meningitis cases in the United States, or approximately 1.1 cases per 100,000 population/year; it is also the leading cause of meningitis following head trauma, skull fractures and CSF leakage. 1, 2, 4, 5

The exact pathogenesis of pneumococcal meningitis remains unclear. The process begins by pneumococcal colonization of the nasopharynx, which can be followed by invasion into the perivascular space, bacteremia with subsequent seeding of the choroid plexus and breach of either the blood-brain barrier or the blood-CSF barrier by as yet unknown mechanisms. Direct extension of Streptococcus pneumoniae from the sinuses or middle ear into the subarachnoid space, particularly in trauma cases, represents an alternative route of CSF access. 2, 4, 5

Pneumococci can multiply rapidly in the CSF due to the absence of effective host defense mechanisms within it. 4, 5 However, it is not the pathogen itself that causes neurological complications, rather, it is the inflammatory reaction towards the invading pathogen that is responsible for the observed tissue damage and clinical manifestations of meningoencephalitis. 2, 3, 5

The polysaccharide capsule of Streptococcus pneumoniae lacks inflammatory potential and acts mainly as a protection against phagocytosis. The peptidoglycan and teichoic acid constituents of the pneumococcal cell wall are critical inducers of the inflammatory response. Lyses of bacteria and release of cell wall components in the subarachnoid space stimulates production of cytokines and chemokines by microglia, astrocytes, monocytes, microvascular endothelial cells and white blood cells (WBCs) in the CSF. The resulting inflammatory processes alter the permeability of the blood-brain barrier, leading to cerebral edema and leakage of serum proteins into the CSF, contributing to the formation of a purulent exudate in the subarachnoid space. The purulent exudate impedes the flow of CSF causing interstitial edema, obstructive and communicating hydrocephalus; it also engulfs the large arteries at the base of the brain causing vasculitis with narrowing of the arterial lumens, which, in turn, results in cerebral ischemia. The inflammatory process can involve the venous system leading to thrombosis of the major sinuses and thrombophlebitis of cerebral cortical veins. Increased intracranial pressure, resulting from cerebral edema, alterations of CSF hemodynamics and loss of cerebrovascular autoregulation, is an important consequence of the inflammatory reaction, and one which leads to further cerebral ischemia. 2, 3, 5

Direct neurotoxicity is another important mechanism of brain damage in pneumococcal meningoencephalitis. Pneumolysin, cytokines and other bacterial components and inflammatory agents induce the production of excitatory amino acids (such as glutamate), reactive oxygen and nitrogen agents (free oxygen radicals, nitric oxide, peroxynitrite, etc.) and other mediators in the brain which bring about massive apoptosis of brain cells. 2, 3, 5

Bacterial meningitis classically presents with a triad of headache, fever and stiff neck. The stiff neck is a result of inflammation surrounding and involving spinal nerves and nerve roots; it is a pathognomonic sign of meningeal irritation that can occasionally be absent. Other signs and symptoms that can be seen in bacterial meningitis include: lethargy, altered mental status, focal neurologic deficits, seizure activity, coma, nausea, vomiting, and photophobia, in addition to findings related to increased intracranial pressure such as papilledema. The disease may progress rapidly, over a few hours, or it may become progressively worse over several days. 2, 5, 6, 7

Neuroimaging does not usually aid in the diagnoses of purulent meningitis, but can be useful in diagnosing complications such as abscesses, hydrocephalus or ischemia. 5, 7 The "gold standard" for diagnosis of bacterial meningitis is direct examination, chemical analysis, gram stain and culture of the CSF. Cerebrospinal fluid abnormalities in bacterial meningitis include a markedly increased opening pressure (>180 mm H2O), increased presence of white blood cells (normal: 0-5 lymphocytes/ mm3, bacterial meningitis: 10 - 10,000 WBCs/mm3 with polymorphonuclear predominance), decreased glucose content (normal: 45-85, bacterial meningitis: < 40 mg/dL) and increased protein concentration (normal: 15-45, bacterial meningitis: >50 mg/dL). Red blood cells (RBCs) are usually absent from both normal and bacterial meningitis CSF; however, RBCs can be seen in both cases if the spinal tap was traumatic. Not all cases of bacterial meningitis have typical CSF findings, and some values, particularly glucose concentration, need to be interpreted within the clinical context. CSF glucose values are normally 50-70% of blood glucose values, therefore, use of a CSF/serum glucose ratio can correct for a decreased CSF glucose value masked by hyperglycemia. A CSF/serum glucose ratio of 0.31 or less is highly suggestive of bacterial meningitis. 5, 6 Gram stains of the CSF show gram-positive cocci in 70 to 90+ % of untreated pneumococcal meningitides; blood or CSF cultures are almost always positive in these cases as well. Tests to detect pneumococcal antigens in the CSF, such as latex agglutination (LA), are useful in the diagnosis of bacterial meningitis in patients who have already been started on antibiotic therapy, and in whom the gram stain and culture results are negative. However, a negative LA test does not rule out bacterial meningitis because the sensitivity of these tests may not always high enough. 2, 5, 6

The initial treatment of pneumococcal meningitis consists of supportive therapy and anti-microbials, including vancomycin (because of its certain anti-microbial efficacy) and a ß-lactam (because it crosses the blood-brain barrier reliably and the organism may be susceptible to it). However, susceptibility testing of the cultured Streptococcus pneumoniae strain must be performed, and therapeutic agents modified accordingly, for definitive anti-microbial treatment. 2, 5, 6


  1. Koneman EW; Allen SD; Janda WM; Schreckenberger PC; Winn Jr WC. Color Atlas and Textbook of Diagnostic Microbiology, 5th edition: Lippincott Williams & Wilkins, 1997.
  2. Musher DM. Streptococcus pneumoniae. In: Mandell, Bennett and Dolin, ed. Principles and Practice of Infectious Diseases. Vol. 2: Churchill Livingstone, 2000:2128-2147.
  3. Gillespie SH, Balakrishnan I. Pathogenesis of pneumococcal infection. J Med Microbiol 2000; 49:1057-67.
  4. Meli DN, Christen S, Leib SL, Tauber MG. Current concepts in the pathogenesis of meningitis caused by Streptococcus pneumoniae. Curr Opin Infect Dis 2002; 15:253-7.
  5. Roos KL. Acute bacterial meningitis. Semin Neurol 2000; 20:293-306.
  6. Tierney LM, McPhee SJ, Papadakis MA, ed. Current Medical Diagnosis & Treatment 2002: Appleton & Lange, 2002.
  7. Gray F, Nordmann P. Bacterial infections. In: Graham DI, Lantos PL, ed. Greenfield's Neuropathology, 6th edition: Arnold, 1997.

Contributed by Suzanne Bakdash, MD, MPH, Marta Couce, MD , PhD, Larry Nichols, MD & William Pasculle, ScD

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