Meningitis is a potentially fatal inflammation of the meninges, the thin, membranous covering of the brain and the spinal cord. Meningitis is most commonly caused by infection (by bacteria, viruses, or fungi), although it can also be caused by bleeding into the meninges, cancer, or diseases of the immune system.

History

Before antibiotics were available, bacterial meningitis was a dreaded disease, taking a toll on the young and leaving those who survived blind, deaf, or mentally retarded. A pioneer in the research of this disease and its cure was Dr. Sara Elizabeth Branham (1888–1962), who worked at the National Institute of Health in the early part of the twentieth century. Initially, she performed research on bacterially caused food poisoning; but after the epidemic years of World War I (1914–1918), she worked on the specific antiserum to combat meningitis. During World War I, cases of the disease ran rampant among soldiers, often leading to lengthy quarantines to prevent its further spread. Knowing that many strains of infectious bacteria could be responsible, Branham developed laboratory procedures that enabled technicians to determine which type of infection was present. At that time, the only treatment for meningitis was an antiserum (developed from horses) that had been losing its effectiveness over the years. Branham substituted a more effective serum extracted from rabbits. In 1937, Branham and a coworker discovered that the newly developed sulfonamide drugs (sulfonamides) were effective in treating meningitis. Sulfadiazine was then used along with antiserum as an effective treatment and was responsible for keeping meningitis at bay during World War II (1939–1945). Branham wrote widely about the disease and was recognized for her dedicated work with awards and honorary degrees.

Anatomical considerations

The meninges are three separate membranes, layered together, which serve to encase the brain and spinal cord. The dura is the toughest, outermost layer, and is closely attached to the inside of the skull. The middle layer, the arachnoid, is important in the normal flow of the cerebrospinal fluid (CSF), a lubricating fluid that bathes both the brain and the spinal cord. The innermost layer, the pia, helps direct brain blood vessels into the brain. The space between the arachnoid and the pia contains CSF, which serves to help insulate the brain from trauma. Through this space course many blood vessels.

CSF, produced within specialized chambers deep inside the brain, flows over the surface of the brain and spinal cord. This fluid serves to cushion these relatively delicate structures, as well as supplying important nutrients for brain cells. CSF is reabsorbed by blood vessels which are located within the meninges.

Because the brain is enclosed in the hard, bony case of the skull, any disease process that produces swelling will ultimately prove destructive to the brain. The skull cannot expand at all, so when swollen brain tissue pushes up against the skull’s hard bone, the brain tissue becomes damaged and may ultimately die. Furthermore, swelling on the right side of the brain will not only cause pressure and damage to that side of the brain, but by taking up precious space within the tight confines of the skull, the left side of the brain will also be pushed up against the hard surface of the skull. This action causes reciprocal damage to that side of the brain as well.

The cells of the brain require a very well-regulated environment for optimal function. Careful balance of oxygen, carbon dioxide, glucose (sugar), sodium, calcium, potassium, and other substances must be maintained in order to avoid damage to the relatively unforgiving brain tissue.

The cells lining the brain’s capillaries (tiny blood vessels) are specifically designed to prevent many substances from passing into brain tissue. This is commonly referred to as the blood-brain barrier. The blood-brain barrier prevents various toxins (substances which could be poisonous to brain tissue), as well as many agents of infection, from crossing from the blood stream into the brain tissue. While this barrier obviously is an important protective feature for the brain, it also serves to complicate therapy in the case of an infection, by making it difficult for medications to pass out of the blood and into the brain tissue where the infection resides.

Infectious causes of meningitis

The most common infectious causes of meningitis vary according to an individual host’s age, habits and living environment, and health status. In newborns, the most common agents of meningitis are those which are contracted from the newborn’s mother, including Group B streptococci (becoming an increasingly common infecting organism in the newborn period), Escherichia coli, and Listeria monocytogenes. Older children are more frequently infected by Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae, while adults are infected by S. pneumoniae and N. meningitidis. N. meningitidis is the only organism that can cause epidemics of meningitis. These have occurred in particular when a child in a crowded day-care situation or a military recruit in a crowded training camp has fallen ill with N. meningitidis meningitis.

Viral causes of meningitis include the herpes simplex viruses, mumps and measles viruses (against which most children are protected due to mass immunization programs), the virus that causes chicken pox, the rabies virus, and a number of viruses that are acquired through the bite of infected mosquitoes. Patients with AIDS (acquired immune deficiency syndrome) are more susceptible to certain infectious causes of meningitis, including by certain fungal agents, as well as by the agent that causes tuberculosis. Patients who have had their spleens removed, or whose spleens are no longer functional (as in the case of patients with sickle cell disease) are more susceptible to certain infections, including those caused by N. meningitidis and S. pneumoniae.

How the infectious agents of meningitis gain access to the meninges

The majority of meningitis infections are acquired by blood-borne spread. An individual may have another type of infection (of the lungs, throat, or tissues of the heart) caused by an organism that can also cause meningitis. The organism multiplies, finds its way into the blood stream, and is delivered in sufficient quantities to invade past the blood-brain barrier.

Direct spread occurs when an already resident infectious agent spreads from infected tissue next to or very near the meninges, for example from an ear or sinus infection. Patients who suffer from skull fractures provide openings to the sinuses, nasal passages, and middle ears. Organisms that frequently live in the human respiratory system can then pass through these openings to reach the meninges and cause infection. Similarly, patients who undergo surgical procedures or who have had foreign bodies surgically placed within their skulls (such as tubes to drain abnormal amounts of accumulated CSF) have an increased risk of the organisms causing meningitis being introduced to the meninges.

The least common method by which the organisms causing meningitis are transmitted, but one of the most interesting, is called intraneural spread. This involves an organism spreading along a nerve, and using that nerve as a kind of ladder into the skull where the organism can multiply and cause meningitis. Herpes simplex virus is known to use this type of spread, as is the rabies virus.

Symptoms of meningitis

The most classic symptoms of meningitis (particularly of bacterial meningitis) include fever, headache, vomiting, photophobia (sensitivity to light), irritability, lethargy (severe fatigue), and stiff neck. The disease progresses with seizures, confusion, and eventually coma.

A young infant may not show the classic signs of meningitis. Early in infancy, a baby’s immune system is not yet developed enough to mount a fever in response to infection, so fever may be absent. Some infants with meningitis have seizures as their only identifiable symptom.

How meningitis damages the brain

Damage due to meningitis occurs from a variety of phenomena. The action of infectious agents on the brain tissue is one direct cause of damage. Other types of damage may be due to mechanical effects of swelling of brain tissue, and compression against the bony surface of the skull. Swelling of the meninges may interfere with the normal absorption of CSF by blood vessels, causing accumulation of CSF and damage due to resulting pressure on the brain. Interference with the brain’s carefully regulated chemical environment may cause damaging amounts of normally present substances (carbon dioxide, potassium) to accumulate. Inflammation may cause the blood-brain barrier to become less effective at preventing the passage of toxic substances into brain tissue.

Long term complications of meningitis

The most frequent long-term effects of meningitis include deafness and blindness, due to compression of specific nerves and brain areas responsible for the senses of hearing and sight. Some patients develop permanent seizure disorders, requiring lifetime treatment with anti-seizure medications. Scarring of the meninges may result in obstruction of the normal flow of CSF, causing abnormal accumulation of CSF. This may be a chronic problem for some patients, requiring the installation of tubes to regularly drain the accumulation.

Diagnosis

A number of techniques are used when examining a patient suspected of having meningitis to verify the diagnosis. Certain manipulations of the head (lowering the head, chin towards chest, for example) are difficult to perform and painful for a patient with meningitis.

The most important test used to diagnosis meningitis is the lumbar puncture (commonly called a spinal tap). Lumbar puncture (LP) involves the insertion of a thin needle into a space between the vertebrae in the lower back, and the withdrawal of a small amount of CSF. The CSF is then examined under a microscope. Normal CSF contains set percentages of glucose and protein. These percentages will vary with bacterial, viral, or other causes of meningitis. For example, bacterial meningitis causes a greatly lower than normal percentage of glucose to be present in CSF, as the bacteria are essentially eating the host’s glucose, and using it for their own nutrition and energy production. Normal CSF should contain no white blood cells (infection fighting cells), so the presence of white blood cells in CSF is another indication of meningitis. Some of the withdrawn CSF is also put into special laboratory dishes to allow growth of the infecting organism, which can then be identified more easily.

In a few rare instances, lumbar puncture cannot be performed, because the amount of swelling within the skull is so great that the intracranial pressure (pressure within the skull) is extremely high. This pressure is always measured immediately upon insertion of the LP needle. If it is found to be very high, no fluid is withdrawn, because withdrawal of fluid could cause herniation of the brain stem. Herniation of the brain stem occurs when the part of the brain connecting to the spinal cord is thrust through the opening at the base of the skull into the spinal canal. Such herniation will cause compression of those structures within the brain stem that control the most vital functions of the body (breathing, heartbeat, consciousness). Death or permanent debilitation follows herniation of the brain stem.

Treatment

Antibiotic medications (forms of penicillins and cephalosporins, for example) are the most important element of treatment against bacterial agents of meningitis. Because of the effectiveness of the blood-brain barrier in preventing passage of substances into the brain, medications must be delivered directly into the patient’s veins (intravenous or IV) at very high doses. Antiviral medications (acyclovir) may be helpful in the case of viral meningitis, and antifungal medications are available as well.

Other treatment for meningitis involves decreasing inflammation (with steroid preparations) and paying careful attention to the balance of fluids, glucose, sodium, potassium, oxygen, and carbon dioxide in the patient’s system. Patients who develop seizures will require medications to halt the seizures and prevent their return.

KEY TERMS

Blood-brain barrier —A blockade of cells separating the circulating blood from elements of the central nervous system (CNS); it acts as a filter, preventing many substances from entering the central nervous system.

Cerebrospinal fluid (also called CSF) —Fluid made in chambers within the brain; this fluid then flows over the surface of the brain and spinal cord, providing nutrition to cells of the nervous system, as well as cushioning.

Lumbar puncture (also called LP) —A medical test in which a very narrow needle is inserted into a specific space between the vertebrae of the lower back in order to draw off and examine a sample of CSF.

Meninges —The three layer membranous covering of the brain and spinal cord, composed of the dura, arachnoid, and pia. Provides protection for the brain, as well as housing many blood vessels.

Prevention

A series of vaccines against Haemophilus influenzae, started at two months of age, has greatly reduced the incidence of that form of meningitis. Vaccines also exist against Neisseria meningitidis and Streptococcus pneumoniae bacteria, but these vaccines are only recommended for those people who have particular susceptibility to those organisms, due to certain immune deficiencies, lack of a spleen, or sickle cell anemia.

Because N. meningitidis is known to cause epidemics of disease, close contacts of patients with such meningitis (other children in day care with the patient, other military personnel within the same training camp, and people living within the patient’s household), are treated with Rifampin^® (or rifampicin). This generally prevents spread of the disease.

Mothers with certain risk factors may be treated with antibiotics during labor, to prevent the passage of certain organisms which may cause meningitis in the newborn (particularly Group B streptococcus).

Resources

BOOKS

Andreoli, Thomas E., et al. Cecil Essentials of Medicine. Philadelphia: W.B. Saunders Company, 2004.

Cormican, M.G. and M.A. Pfaller. “Molecular Pathology of Infectious Diseases,” in Clinical Diagnosis and Management by Laboratory Methods. 20th ed. Philadelphia: W. B. Saunders, 2001.

Janner, Donald. A Clinical Guide to Pediatric Infectious Disease. Philadelphia, PA: Lippincott Williams & Wilkins, 2005.

Kasper, Dennis L., et al. Harrison’s Principles of Internal Medicine. New York: McGraw Hill, Medical Pub. Division, 2005.

Kobayashi, G., Patrick R. Murray, Ken Rosenthal, and Michael Pfaller. Medical Microbiology. St. Louis, MO: Mosby, 2003.

Koch, A.L. Bacterial Growth and Form Dordrecht: Kluwer Academic Publishers, 2001.

The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck, 2006.

Richman, D.D., and R.J. Whitley. Clinical Virology. 2nd ed. Washington: American Society for Microbiology, 2002.

Shmaefsky, Brian. Meningitis. Philadelphia, PA: Chelsea House Publishers, 2005.

Tunkel, Allan R. Bacterial Meningitis. Philadelphia: Lippincott Williams & Wilkins, 2001.

PERIODICALS

“Epidemics Of Meningococcal Disease. African Meningitis Belt, 2001.” Weekly Epidemiological Record/World Health Organization 76, no. 37 (2001): 282-288.

Tsukahara, Hirokazu. “Oxidant And Antioxidant Activities In Childhood Meningitis.” Life Sciences 71, no. 23 (2002): 2797.

Rosalyn Carson-DeWitt

The Gale Encyclopedia of Science