Meningitis

Definition

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 , diseases of the immune system, and an inflammatory response to certain types of chemotherapy or other chemical agents. The most serious and the most difficult to treat types of meningitis tend to be those caused by bacteria.

Description

Meningitis is a particularly dangerous infection because of the very delicate nature of the brain. Brain cells are some of the only cells in the body that, once killed, will not regenerate themselves. Therefore, if enough brain tissue is damaged by an infection, then serious lifelong handicaps will remain.

In order to learn about meningitis, it is important to have a basic understanding of the anatomy of the brain. The meninges are three separate membranes, layered together, which 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 because of its involvement in the normal flow of the cerebrospinal fluid (CSF), a lubricating and nutritive fluid that bathes both the brain and the spinal cord.
• The innermost layer, the pia, helps direct blood vessels into the brain.
• The space between the arachnoid and the pia contains CSF, which helps insulate the brain from trauma. Many blood vessels, as well as peripheral and cranial nerves course through this space.

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 located within the meninges. A careful balance between CSF production and reabsorption is important to avoid the accumulation of too much CSF.

Because the brain is enclosed in the hard, bony case of the skull, any disease that produces swelling will be damaging to the brain. The skull cannot expand at all, so when the swollen brain tissue pushes up against the skull's hard bone, the brain tissue becomes damaged and the blood supply is compromised, and this tissue 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, causing damage to the left side of the brain, as well.

Another way that infections injure the brain involves the way in which the chemical environment of the brain changes in response to the presence of an infection. The cells of the brain require a very well-regulated environment. Careful balance of oxygen, carbon dioxide, sugar (glucose), sodium, calcium, potassium , and other substances must be maintained in order to avoid damage to brain tissue. An infection upsets this balance, and brain damage can occur when the cells of the brain are either deprived of important nutrients or exposed to toxic levels of particular substances.

The cells lining the brain's tiny blood vessels (capillaries) 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 substances that could be poisonous to brain tissue (toxins), as well as many agents of infection, from crossing from the blood stream into the brain tissue. While this barrier is obviously an important protective feature for the brain, it also serves to complicate treatment 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 is located.

Causes & symptoms

The most common infectious causes of meningitis vary according to an individual's age, habits, living environment, and health status. While nonbacterial types of meningitis are more common, bacterial meningitis is more potentially life-threatening. Three bacterial agents are responsible for about 80% of all bacterial meningitis cases. These bacteria are Haemophilus influenzae type b, Neisseria meningitidis (causing meningococcal meningitis), and Streptococcus pneumoniae (causing pneumococcal meningitis).

In newborns, the most common agents of meningitis are those that 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. The highest incidence of meningitis occurs in babies under a month old, with an increased risk of meningitis continuing through about two years of age.

Older children are more frequently infected by bacteria, including Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae.

Adults are most commonly infected by either S. pneumoniae or N. meningitidis, with pneumococcal meningitis the more common. Certain conditions predispose to this type of meningitis, including alcoholism and chronic upper respiratory tract infections (especially of the middle ear, sinuses, and mastoids).

N. meningitidis is the only organism that can cause epidemics of meningitis. For instance, cases have been reported when a child in a crowded day care situation or a military recruit in a crowded training camp has fallen ill with meningococcal meningitis.

There have been case reports in recent years of meningitis caused by Streptococcus bovis, an organism that is ordinarily found in the digestive tract of such animals as cows and sheep; and Pasteurella multocida, an organism that usually infects rabbits. Other atypical cases of meningitis include several caused by the anthrax bacillus. These cases have a high mortality rate.

Viral causes of meningitis include the herpes simplex virus, the mumps and measles viruses (against which most children are protected due to mass immunization programs), the virus that causes chickenpox , the rabies virus, and a number of viruses that are acquired through the bites of infected mosquitoes.

A number of medical conditions predispose individuals to meningitis caused by specific organisms. Patients with AIDS (acquired immunodeficiency syndrome) are more prone to getting meningitis from fungi, as well as from 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 other infections, including meningococcal and pneumococcal meningitis.

The majority of meningitis infections are acquired by transmission through the blood. A person may have another type of infection (for instance, infection of the lungs, throat, or tissues of the heart) caused by an organism that can also cause meningitis. If this initial infection is not properly treated, the organism will continue to multiply, find its way into the blood stream, and be delivered in sufficient quantities to invade past the blood-brain barrier. Direct spread occurs when an organism spreads to the meninges from infected tissue next to or very near the meninges. This can occur, for example, with a severe, poorly treated ear or sinus infection .

Patients who suffer from skull fractures possess abnormal openings to the sinuses, nasal passages, and middle ears. Organisms that usually live in the human respiratory system without causing disease can pass through openings caused by such fractures, 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 meningitis.

Organisms can also reach the meninges via an uncommon but interesting method called intraneural spread. This involves an organism invading the body at a considerable distance away from the head, spreading along a nerve, and using that nerve as a sort 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.

The classic symptoms of meningitis (particularly of bacterial meningitis) include fever, headache, vomiting , sensitivity to light (photophobia), irritability, severe fatigue (lethargy), stiff neck, and a reddish purple rash on the skin. Untreated, the disease progresses with seizures, confusion, and eventually coma.

A very 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. However, checking an infant's temperature to see if it is high or low could be an indication. Some infants with meningitis have seizures as their only identifiable symptom. Similarly, debilitated elderly patients may not have fever or other identifiable symptoms of meningitis.

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 the mechanical effects of swelling and compression of brain tissue 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 from the 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.

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 diagnose meningitis is the lumbar puncture (LP), commonly called a spinal tap. Lumbar puncture 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 to look for bacteria or fungi. 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 smaller 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 infection-fighting cells (white blood 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 lab dishes to allow growth of the suspected infecting organism, which can then be identified more easily. Special immunologic and serologic tests may also be used to help identify the infectious agent.

In rare instances, CSF from a lumbar puncture cannot be examined because the amount of swelling within the skull is so great that the pressure within the skull (intracranial pressure) 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 doing so 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, heart beat, consciousness). Death or permanent debilitation follows herniation of the brain stem.

Treatment

Because meningitis is a potentially deadly condition, doctors should be contacted immediately for diagnosis and treatment. Alternative treatments should be used only to support the recovery process following appropriate antibiotic treatments, or used concurrently with antibiotic treatments.

General recommendations

Patients should be well rested in bed, preferably in a darkened room. They should be given lots of fluids and nutritious foods. Patients should avoid processed foods and those with high fat and sugar content. Fats are difficult to digest in severely ill patients; sugar tends to depress the immune system and impede recovery process. Patients should also take vitamin A (up to 10,000 IU per day), B-complex vitamins (up to 1,500 mg per day), and vitamin C (up to 2 g per day) to help keep the body strong and prevent future infections. Additionally, the patient may consider taking other antioxidants, essential fatty acids (EFAs), and/or participate in therapies, such as massage therapy and movement therapies (e.g., t'ai chi ).

Other treatments

Alternative therapies, such as homeopathy, traditional Chinese medicine , and Western herbal medicine may help patients regain their health and build up their immune systems. The recovering individual, under the direction of a professional alternative therapist, may opt to include mushrooms into his or her diet to stimulate immune function. Contact an experienced herbalist or homeopathic practitioner for specific remedies.

Allopathic treatment

Antibiotics are the first line of treatment for bacterial meningitis. In recent years, however, doctors have turned to such newer medications as vancomycin or the fluoroquinolones to treat bacterial meningitis because strains of S. pneumoniae and N. meningitidis have emerged that are resistant to penicillin and the older antibiotics. Because of the effectiveness of the blood-brain barrier in preventing the passage of substances into the brain, medications must be delivered directly into the patient's veins (intravenously) at very high doses. Antiviral drugs (acyclovir) may be helpful in shortening the course of viral meningitis, and antifungal medications are available as well. Patients who develop seizures will require medications to halt the seizures and prevent their return.

Expected results

Viral meningitis is the least severe type of meningitis, and patients usually recover with no long-term effects from the infection. Bacterial infections, however, are much more severe, and progress rapidly. Without very rapid treatment with the appropriate antibiotic, the infection can swiftly lead to coma and death in less than a day's time. While death rates from meningitis vary depending on the specific infecting organism, the overall death rate is just under 20%.

The most frequent long-term effects of meningitis include deafness and blindness, which may be caused by the compression of specific nerves and brain areas responsible for the senses of hearing and sight. Some patients develop permanent seizure disorders, requiring lifelong treatment with antiseizure 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 shunt tubes to drain the accumulation regularly.

Some cases of sudden and unexplained death in adults have been attributed to rapidly developing meningitis.

Prevention

Prevention of meningitis primarily involves the appropriate treatment of other infections an individual may acquire, particularly those that have a track record of seeding to the meninges (such as ear and sinus infections). Preventive treatment with antibiotics is sometimes recommended for the close contacts of an individual who is ill with meningococcal or H. influenzae type b meningitis. A meningococcal vaccine exists, and is sometimes recommended to individuals who are traveling to very high risk areas. A vaccine for H. influenzae type b is now given to babies as part of the standard array of childhood immunizations.

Resources

BOOKS

"Meningitis." The Medical Advisor: The Complete guide to Alternative & Conventional Treatments. Home Edition. Richmond, VA: Time Life Inc., 1997.

Ray, C. George. "Central Nervous System Infections." In Sherris Medical Microbiology: An Introduction to Infectious Diseases, edited by Kenneth J. Ryan. Norwalk, CT: Appleton and Lange, 1994.

Swartz, Morton N. "Bacterial Meningitis." In Cecil Textbook of Medicine, edited by J. Claude Bennett and Fred Plum. Philadelphia: W.B. Saunders, 1996.

PERIODICALS

Aronin, S. I. "Current Pharmacotherapy of Pneumococcal Meningitis." Expert Opinion on Pharmacotherapy 3 (February 2002): 121–129.

Black, M., and D. I Graham. "Sudden Unexplained Death in Adults Caused by Intracranial Pathology." Journal of Clinical Pathology 55 (January 2002): 44–50.

Green, B. T., K. M. Ramsey, and P. E. Nolan. "Pasteurella multocida Meningitis: Case Report and Review of the Last 11 Years." Scandinavian Journal of Infectious Disease 34 (2002): 213–217.

Meissner, Judith W. "Caring for Patients With Meningitis." Nursing (July 1995): 50+.

Schuchat, Anne, et al. "Bacterial Meningitis in the United States in 1995." New England Journal of Medicine (October 2, 1997).

Tasyaran, M. A., O. Deniz, M. Ertek, and K. Cetin. "Anthrax Meningitis: Case Report and Review." Scandinavian Journal of Infectious Diseases 34 (2002): 66–67.

Tunkel, A. R., and W. M. Scheld. "Treatment of Bacterial Meningitis." Current Infectious Disease Reports 4 (February 2002): 7–16.

Vilarrasa, N., A. Prats, M. Pujol, et al. "Streptococcus bovis Meningitis in a Healthy Adult Patient." Scandinavian Journal of Infectious Diseases 34 (2002): 61–62.

ORGANIZATIONS

American Academy of Neurology. 1080 Montreal Avenue, St. Paul, MN 55116. (612) 695-1940. <http://www.aan.com>.

Meningitis Foundation of America. 7155 Shadeland Station, Suite 190, Indianapolis, IN 46256-3922. (800) 668-1129. <http://www.musa.org/welcome.htm>.

Mai Tran

Rebecca J. Frey, PhD

Meningitis

History

Anatomical considerations

Infectious causes of meningitis

How the infectious agents of meningitis gain access to the meninges

Symptoms of meningitis

How meningitis damages the brain

Long term complications of meningitis

Diagnosis

Treatment

Prevention

Resources

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

Meningitis

Definition

Meningitis is a serious 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, diseases of the immune system, and an inflammatory response to certain types of chemotherapy or other chemical agents. The most serious and difficult-to-treat types of meningitis tend to be those caused by bacteria. In some cases, meningitis can be a potentially fatal condition.

Description

Meningitis is a particularly dangerous infection because of the very delicate nature of the brain. Brain cells are some of the only cells in the body that, once killed, will not regenerate themselves. Therefore, if enough brain tissue is damaged by an infection, serious, life-long handicaps will remain.

In order to learn about meningitis, it is important to have a basic understanding of the anatomy of the brain. The meninges are three separate membranes, layered together, which 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 because of its involvement in the normal flow of the cerebrospinal fluid (CSF), a lubricating and nutritive fluid that bathes both the brain and the spinal cord.
• The innermost layer, the pia, helps direct blood vessels into the brain.
• The space between the arachnoid and the pia contains CSF, which helps insulate the brain from trauma. Many blood vessels course through this space.

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 located within the meninges. A careful balance between CSF production and reabsorption is important to avoid the accumulation of too much CSF.

Because the brain is enclosed in the hard, bony case of the skull, any disease that produces swelling will be damaging to the brain. The skull cannot expand at all, so when the 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, causing damage to the left side of the brain as well.

Another way that infections injure the brain involves the way in which the chemical environment of the brain changes in response to the presence of an infection. The cells of the brain require a very well-regulated environment. Careful balance of oxygen, carbon dioxide, sugar (glucose), sodium, calcium, potassium, and other substances must be maintained in order to avoid damage to brain tissue. An infection upsets this balance, and brain damage can occur when the cells of the brain are either deprived of important nutrients or exposed to toxic levels of particular substances.

HATTIE ALEXANDER (1901–1968)

Hattie Alexander, a dedicated pediatrician, medical educator, and researcher in microbiology, won international recognition for deriving a serum to combat influenzal meningitis, a common disease that previously had been nearly always fatal to infants and young children. Alexander subsequently investigated microbiological genetics and the processes whereby bacteria, through genetic mutation, acquire resistance to antibiotics. In 1964, as president of the American Pediatric Society, she became one of the first women to head a national medical association.

As an intern at the Harriet Lane Home of Johns Hopkins Hospital from 1930 to 1931, Alexander became interested in influenzal meningitis. The source of the disease was Hemophilus influenzae, a bacteria that causes inflammation of the meninges, the membranes surrounding the brain and spinal cord. In 1931, Alexander began a second internship at the Babies Hospital of the Columbia-Presbyterian Medical Center in New York City. There, she witnessed first-hand the futility of medical efforts to save babies who had contracted influenzal meningitis.

Alexander's early research focused on deriving a serum (the liquid component of blood, in which antibodies are contained) that would be effective against influenzal meningitis. Serums derived from animals that have been exposed to a specific disease-producing bacterium often contain antibodies against the disease and can be developed for use in immunizing humans against it. Alexander knew that the Rockefeller Institute in New York City, however, had been able to prepare a rabbit serum for the treatment of pneumonia, another bacterial disease. Alexander therefore experimented with rabbit serums, and by 1939 was able to announce the development of a rabbit serum effective in curing infants of influenzal meningitis.

In the early 1940s, Alexander experimented with the use of drugs in combination with rabbit serum in the treatment of influenzal meningitis. Within the next two years, she saw infant deaths due to the disease drop by eighty percent.

The cells lining the brain's tiny blood vessels (capillaries) 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 substances that could be poisonous to brain tissue (toxins), as well as many agents of infection, from crossing from the blood stream into the brain tissue. While this barrier is obviously an important protective feature for the brain, it also serves to complicate treatment 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 is located.

Causes and symptoms

The most common infectious causes of meningitis vary according to an individual's age, habits, living environment, and health status. While nonbacterial types of meningitis are more common, bacterial meningitis is the more potentially life-threatening. Three bacterial agents are responsible for about 80% of all bacterial meningitis cases. These bacteria are Haemophilus influenzae type b, Neisseria meningitidis (causing meningococcal meningitis), and Streptococcus pneumoniae (causing pneumococcal meningitis).

In newborns, the most common agents of meningitis are those that 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. The highest incidence of meningitis occurs in babies under a month old, with an increased risk of meningitis continuing through about two years of age.

Older children are more frequently infected by the bacteria Haemophilus influenzae, Neisseria meningitidis, and Streptococci pneumoniae.

Adults are most commonly infected by either S. pneumoniae or N. meningitidis, with pneumococcal meningitis the more common. Certain conditions predispose to this type of meningitis, including alcoholism and chronic upper respiratory tract infections (especially of the middle ear, sinuses, and mastoids).

N. meningitidis is the only organism that can cause epidemics of meningitis. In particular, these have occurred when a child in a crowded day-care situation or a military recruit in a crowded training camp has fallen ill with meningococcal meningitis.

Viral causes of meningitis include the herpes simplex virus, the 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 bites of infected mosquitoes.

A number of medical conditions predispose individuals to meningitis caused by specific organisms. Patients with AIDS (acquired immune deficiency syndrome) are more prone to getting meningitis from fungi, as well as from 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 other infections, including meningococcal and pneumococcal meningitis.

The majority of meningitis infections are acquired by blood-borne spread. A person may have another type of infection (of the lungs, throat, or tissues of the heart) caused by an organism that can also cause meningitis. If this initial infection is not properly treated, the organism will continue to multiply, find its way into the blood stream, and be delivered in sufficient quantities to invade past the blood brain barrier. Direct spread occurs when an organism spreads to the meninges from infected tissue next to or very near the meninges. This can occur, for example, with a severe, poorly treated ear or sinus infection.

Patients who suffer from skull fractures possess abnormal openings to the sinuses, nasal passages, and middle ears. Organisms that usually live in the human respiratory system without causing disease can pass through openings caused by such fractures, 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 meningitis.

Organisms can also reach the meninges via an uncommon but interesting method called intraneural spread. This involves an organism invading the body at a considerable distance away from the head, 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.

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

A very 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. Similarly, debilitated elderly patients may not have fever or other identifiable symptoms of meningitis.

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 the mechanical effects of swelling and compression of brain tissue 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 from the 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.

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 diagnose 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 to look for bacteria or fungi. 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 infection-fighting cells (white blood 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 lab dishes to allow growth of the infecting organism, which can then be identified more easily. Special immunologic and serologic tests may also be used to help identify the infectious agent.

In rare instances, CSF from a lumbar puncture cannot be examined because the amount of swelling within the skull is so great that the pressure within the skull (intracranial pressure) 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 doing so 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, heart beat, consciousness). Death or permanent debilitation follows herniation of the brain stem.

Treatment

Antibiotic medications (forms of penicillin 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 the passage of substances into the brain, medications must be delivered directly into the patient's veins (intravenously, or by IV), at very high doses. Antiviral drugs (acyclovir) may be helpful in shortening the course of viral meningitis, and antifungal medications are available as well.

Other treatments for meningitis involve 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— An arrangement of cells within the blood vessels of the brain that prevents the passage of toxic substances, including infectious agents, from the blood and into the brain. It also makes it difficult for certain medications to pass into brain tissue.

Cerebrospinal fluid (CSF)— Fluid made in chambers within the brain which then flows over the surface of the brain and spinal cord. CSF provides nutrition to cells of the nervous system, as well as providing a cushion for the nervous system structures. It may accumulate abnormally in some disease processes, causing pressure on and damage to brain structures.

Lumbar puncture (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 a sample of CSF for further examination.

Meninges— The three-layer membranous covering of the brain and spinal cord, composed of the dura, arachnoid, and pia. It provides protection for the brain and spinal cord, as well as housing many blood vessels and participating in the appropriate flow of CSF.

Prognosis

Viral meningitis is the least severe type of meningitis, and patients usually recover with no long-term effects from the infection. Bacterial infections, however, are much more severe, and progress rapidly. Without very rapid treatment with the appropriate antibiotic, the infection can swiftly lead to coma and death in less than a day's time. While death rates from meningitis vary depending on the specific infecting organism, the overall death rate is just under 20%.

The most frequent long-term effects of meningitis include deafness and blindness, which may be caused by the compression of specific nerves and brain areas responsible for the senses of hearing and sight. Some patients develop permanent seizure disorders, requiring life-long 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 shunt tubes to drain the accumulation regularly.

Prevention

Prevention of meningitis primarily involves the appropriate treatment of other infections an individual may acquire, particularly those that have a track record of seeding to the meninges (such as ear and sinus infections). Preventive treatment with antibiotics is sometimes recommended for the close contacts of an individual who is ill with meningococcal or H. influenzae type b meningitis. A meningococcal vaccine exists, and is sometimes recommended to individuals who are traveling to very high risk areas. A vaccine for H. influenzae type b is now given to babies as part of the standard array of childhood immunizations.

Resources

ORGANIZATIONS

American Academy of Neurology. 1080 Montreal Ave., St. Paul, MN 55116. (612) 695-1940. 〈http://www.aan.com〉.

Meningitis Foundation of America. 7155 Shadeland Station, Suite 190, Indianapolis, IN 46256-3922. (800) 668-1129. 〈http://www.musa.org/welcome.htm〉.

Meningitis

Definition

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 (bacteria, viruses, or fungi ), although it can also be caused by bleeding into the meninges, cancer, diseases of the immune system, and an inflammatory response to certain types of chemotherapy or other chemical agents. The most serious and difficult-to-treat types of meningitis tend to be those caused by bacteria.

Description

Meningitis is a particularly dangerous infection because of the very delicate nature of the brain. Brain cells are among a very small number of cells in the body that, once killed, will not regenerate. Therefore, if enough brain tissue is damaged, serious, life-long handicaps may remain.

To understand meningitis, it is important to have a basic understanding of the anatomy of the brain. The meninges are three separate membranes layered together that encase the brain and spinal cord:

• The dura is the toughest, outermost layer, and is closely attached to the inside of the skull.
• The arachnoid, the middle layer, is important because of its involvement in the normal flow of the cerebrospinal fluid (CSF), a lubricating and nutritive fluid that bathes both the brain and the spinal cord.
• The pia, the innermost layer, helps direct blood vessels into the brain.

The space between the arachnoid and the pia contains CSF, which helps insulate the brain from trauma. Many blood vessels course through this space.

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 to supply important nutrients for brain cells. CSF is reabsorbed by blood vessels located within the meninges. A careful balance between CSF production and reabsorption is important to avoid the accumulation of too much CSF.

Because the brain is enclosed in the hard, bony case of the skull, any disease that produces swelling of the brain will be damaging. The skull cannot expand at all; so, when any swollen brain tissue pushes up against the skull's hard bone, brain tissue may become damaged and ultimately die. Swelling on one side of the brain will not only cause pressure and damage to that side of the brain, but, because it takes up precious space within the tight confines of the skull, the opposite side of the brain will also be pushed against the skull, causing damage to that side also.

Another way that infections injure the brain involves the way the chemical environment of the brain changes in response to that infection. Brain cells require a very well-regulated environment. Careful balance of oxygen, carbon dioxide, sugar (glucose), sodium, calcium, potassium, and other substances must be maintained to avoid damage to brain tissue. An infection upsets this balance. Brain damage can occur when cells are either deprived of important nutrients or exposed to toxic levels of particular substances.

The cells lining the brain's tiny blood vessels (capillaries) 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 substances that could be harmful to brain tissue (toxins), as well as many agents of infection, from crossing from the blood stream into the brain tissue. While this barrier is obviously an important protective feature for the brain, it also serves to complicate treatment in the case of an infection by making it difficult for medications to pass out of the blood and into the brain tissue where an infection is located.

Causes and symptoms

The most common infectious causes of meningitis vary according to an individual's age, habits, living environment, and health status. While nonbacterial types of meningitis are most common, bacterial meningitis is the more potentially life threatening. Three bacterial agents are responsible for about 80% of all bacterial meningitis cases. These bacteria are Haemophilus influenzae type b, Neisseria meningitidis (causing meningococcal meningitis), and Streptococcus pneumoniae (causing pneumococcal meningitis).

In newborns, the most common agents of meningitis are those contracted from the newborn's mother, including Group B streptococci (which is becoming an increasingly common infecting organism in the new-born period), Escherichia coli, and Listeria monocytogenes. The highest incidence of meningitis occurs in babies younger than a month old, with an increased risk of meningitis continuing through about two years of age.

Older children are more frequently infected by the bacteria Haemophilus influenzae, Neisseria meningitidis, and Streptococci pneumoniae.

Adults are most commonly infected by either S. pneumoniae or N. meningitidis, with pneumococcal meningitis the most common. Certain conditions predispose an individual to this type of meningitis, including alcoholism and chronic upper respiratory tract infections (especially of the middle ear, sinuses, and mastoids).

N. meningitidis is the only organism that can cause epidemics of meningitis. In particular, these appear to occur when a child in a crowded day-care situation, or a military recruit in a crowded training camp, has fallen ill with meningococcal meningitis.

Viral causes of meningitis include the herpes simplex virus, the 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 bites of infected mosquitoes.

A number of medical conditions predispose individuals to meningitis caused by specific organisms. People with AIDS (acquired immunodeficiency syndrome) are more prone to getting meningitis from fungi, as well as from the agent that causes tuberculosis. Persons who have had their spleens removed, or whose spleens are no longer functional (as in the case of individuals with sickle cell disease ) are more susceptible to meningococcal and pneumococcal meningitis.

The majority of meningitis infections are acquired by blood-borne spread. A person may have another type of infection (of the lungs, throat, or tissues of the heart ) caused by an organism that can also cause meningitis. If this initial infection is not properly treated, the organism will continue to multiply, find its way into the blood stream, and be delivered in sufficient quantities to pass the blood brain barrier. Direct spread occurs when an organism spreads to the meninges from infected tissue next to or very near the meninges. This can occur, for example, with a severe, poorly treated ear or sinus infection.

Persons who suffer from skull fractures possess abnormal openings to the sinuses, nasal passages, and middle ears. Organisms that usually live in the human respiratory system without causing disease can pass through such openings, reach the meninges, and cause infection. Similarly, people 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 meningitis.

Organisms can also reach the meninges via an uncommon but interesting method called intraneural spread. This involves an organism invading the body at a considerable distance away from the head, spreading along a nerve, and using that nerve as a 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.

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

A very 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. In some infants with meningitis, seizures are the only identifiable symptom. Similarly, debilitated elderly people may not have fever or other identifiable symptoms of meningitis.

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 the mechanical effects of swelling and compression of brain tissue against the skull. Swelling of the meninges may interfere with the normal absorption of CSF by blood vessels, causing accumulation of CSF and damage from the resulting pressure on the brain. Interference with the brain's carefully regulated chemical environment may cause abnormal and 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.

Diagnosis

A number of techniques are used when examining a person 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 person with meningitis.

The most important test used to diagnose 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 to look for bacteria or fungi. 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 decreased percentage of glucose in the CSF because the bacteria are essentially consuming or "eating" that glucose and using it for their own nutrition and energy production. Normal CSF should contain no infection-fighting cells (white blood cells), so the presence of white blood cells in CSF is another indication of meningitis. Some of the withdrawn CSF is put into special lab dishes to allow growth of the infecting organism, which can then be identified more easily. Special immunologic and serologic tests may also be used to help identify the infectious agent.

In rare instances a lumbar puncture cannot be performed because of the amount of swelling and pressure within the skull (intracranial pressure). This pressure is measured immediately upon insertion of an LP needle. If it is found to be high, no fluid is withdrawn because doing so 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, heart beat, consciousness). Death or permanent debilitation follows herniation of the brain stem.

Treatment

Antibiotic medications (forms of penicillin and cephalosporins, for example) are the most important elements of treatment against bacterial meningitis. Because of the effectiveness of the blood-brain barrier in preventing passage of substances into the brain, medications must be delivered directly into an affected person's veins (intravenously, or IV), at very high doses. Antiviral drugs (acyclovir) may be helpful in shortening the duration of viral meningitis, and antifungal medications are also available.

Other treatments involve decreasing inflammation (with steroid preparations) and paying careful attention to the balance of fluids, glucose, sodium, potassium, oxygen, and carbon dioxide in a person's system. People who develop seizures will require medications to halt the seizures and prevent their return.

Prognosis

Viral meningitis is the least severe type, and persons usually recover with no long-term effects from the infection. Bacterial infections, however, are much more severe, and rapidly progress. Without very rapid treatment with the appropriate antibiotic, an infection can swiftly lead to coma and death, often in less than 24 hours. While death rates from meningitis vary depending upon the specific infecting organism, the overall death rate is just under 20%.

The most frequent long-term effects of meningitis include deafness and blindness, which may be caused by the compression of specific nerves and brain areas responsible for the senses of hearing and sight. Some people develop permanent seizure disorders, requiring life-long treatment with antiseizure 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 people, requiring the installation of shunt tubes to drain the accumulation on a regular basis.

Health care team roles

Family physicians, pediatricians, emergency physicians, or internists usually make the initial diagnosis of meningitis. Laboratory technicians identify organisms that cause meningitis. Nurses and other hospital staff provide supportive care, and patient and family education. Occasionally, physical therapists are needed to help the patient recover lost muscle functioning.

KEY TERMS

Arachnoid mater— The middle layer of the meninges.

Blood-brain barrier— An arrangement of cells within the blood vessels of the brain that prevents toxic substances, infectious agents, and many medications, from passing from the blood into the brain.

Cerebrospinal fluid (CSF)— Fluid made in chambers within the brain which then flows over the surface of the brain and spinal cord. CSF provides nutrition to cells of the nervous system, as well as providing a cushion for the nervous system structures.

Dura mater— The outermost layer of the meninges.

Lumbar puncture (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 obtain a sample of CSF for examination.

Meninges— The three-layer membranous covering of the brain and spinal cord, composed of the dura, arachnoid, and pia. It provides protection for the brain and spinal cord, as well as housing many blood vessels and participating in the appropriate flow of CSF.

Photophobia— Abnormal sensitivity to light.

Pia mater— The innermost layer of the meninges.

Prevention

Prevention of meningitis primarily involves the appropriate treatment of other infections an individual may acquire, particularly those known to seed to the meninges (such as ear and sinus infections). Preventive treatment with antibiotics is sometimes recommended for those in close contacts with an individual who is ill with meningococcal or H. influenzaetype b meningitis. A meningococcal vaccine is sometimes recommended to individuals traveling to very high risk areas. A vaccine for H. influenzae type b is now given to babies as part of the standard array of childhood immunizations.

Resources

BOOKS

Adams, Raymond D, Maurice Victor, and Allan H. Ropper. Adam's & Victor's Principles of Neurology, 6th ed. New York: McGraw Hill, 1997.

Koroshetz, Walter J, and Morton N. Swartz. "Chronic and Rrecurrent Meniingitis." In Harrison's Principles of Internal Medicine, 14th ed. Ed. Anthony S. Fauci, et al. New York: McGraw-Hill, 1998, 2434-2439.

Nath, Avindra, and Joseph R. Berger. "Acute Viral Meningitis and Encephalitis." In Cecil Textbook of Medicine, 21st ed. Ed. Lee Goldman and J. Claude Bennett. Philadelphia: W.B. Saunders, 2000, 2123-2126.

Pollard, Andrew J., and Martin C. J. Maiden. Meningococcal Disease: Methods and Protocols. Totowa: Humana Press, 2001.

Prober, Charles G. "Acute Bacterial Meningitis Beyond the Neonatal Period." In Nelson Textbook of Pediatrics 16th ed. Ed. Richard E. Behrman et al., Philadelphia: Saunders, 2000, 751-757.

――――――. "Eosinophilic Meningitis." In Nelson Textbook of Pediatrics 16th ed. Ed. Richard E. Behrman et al., Philadelphia: Saunders, 2000, 760-761.

――――――. "Viral Meningoencephalitis." In Nelson Textbook of Pediatrics 16th ed. Ed. Richard E. Behrman et al., Philadelphia: Saunders, 2000, 757-760.

Scheld, W. Michael. "Bacterial Meningitis, Brain Abscess, and Other Suppurative Intracranial Infections." In Harrison's Principles of Internal Medicine 14th ed. Ed. Anthony S. Fauci, et al. New York: McGraw-Hill, 1998, 2419-2434.

Tyler, Kenneth L. "Aseptic Meningitis, Viral Encephalitis, and Prion Diseases." In Harrison's Principles of Internal Medicine 14th ed. Ed. Anthony S. Fauci, et al. New York: McGraw-Hill, 1998, 2451-2457.

PERIODICALS

Agarwal, R., and A. J. Emmerson. "Should Repeat Lumbar Punctures be Routinely Done in Neonates with Bacterial Meningitis? Results of a Survey into Clinical Practice." Archives of Diseases of Children 84, no. 5 (2001): 451-452.

Colby, C. E., W. J. Steinbach, and A. K. Haiman. "A 10-week Old Infant with Meningitis." Clinics in Pediatrics 40, no. 3 (2001): 155-158.

Glennie, L. "Meningitis: A Rash Diagnosis." Nursing Times 96, no. 12 (2000): 44-45.

Kerr, C. "Meningitis Hits West Africa." Trends in Microbiology 9, no. 5 (2001): 203-205.

van den Berg, H., M. van der Flier, and M. D. van de Wetering. "Cytarabine-Induced Aseptic Meningitis." Leukemia 15, no. 4 (2001): 697-699.

von Vigier, R. O., S. M. Colombo, P. B. Stoffel, P. Meregalli, A. C. Truttmann, and M. G. Bianchetti. "Circulating Sodium in Acute Meningitis." American Journal of Nephrology 21. no. 2 (2001): 87-90.

ORGANIZATIONS

American Academy of Emergency Medicine. 611 East Wells Street, Milwaukee, WI 53202. (800) 884-2236. 〈http://www.aaem.org〉.

Meningitis Foundation of America Inc. 7155 Shadeland Station, Suite 190, Indianapolis, Indiana 46256-3922. (800) 668-1129 or (317) 595-6383. 〈http://www.musa.org/default.htm〉.

OTHER

American Academy of Family Practice. 〈http://www.aafp.org/afp/990515ap/2761.html.,〉 and 〈http://www.aafp.org/afp/971001ap/tunkel.html〉.

Association of State and Territorial Directors of Health Promotion and Public Health Education. 〈http://www.astdhpphe.org/infect/bacmeningitis.html〉.

Centers for Disease Control and Prevention. 〈http://www.cdc.gov/od/oc/media/pressrel/r991021.htm.,〉 and 〈http://www.cdc.gov/ncidod/dbmd/diseaseinfo/meningococcal_g.htm〉.

Meningitis Research Foundation of UK. 〈http://www.meningitis.org.uk〉.

National Institute for Medical Research (UK). 〈http://www.nimr.mrc.ac.uk/MillHillEssays/1999/meningitis.htm〉.

National Institute of Neurological Disorders and Stroke. 〈http://www.ninds.nih.gov/health_and_medical/disorders/encmenin_doc.htm〉.

National Library of Medicine. 〈http://www.nlm.nih.gov/medlineplus/meningitis.html〉.

National Meningitis Trust of UK. 〈http://www.meningitis-trust.org.uk/frame.htm〉.

University of Illinois School of Medicine. 〈http://www.mckinley.uiuc.edu/health-info/dis-cond/commdis/meningit.html〉.

University of Maryland College of Medicine. 〈http://umm.drkoop.com/conditions/ency/article/000680.htm〉.

Meningitis

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 .

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 which 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 which 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, causing 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 ofoxygen , 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 which causes chicken pox, the rabies virus, and a number of viruses which 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 which 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 which 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 which 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 very 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 life-time 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 lab 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, heart beat, 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.

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. 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, 1993.

Berkow, Robert, and Andrew J. Fletcher. The Merck Manual of Diagnosis and Therapy. Rahway, NJ: Merck Research Laboratories, 1992.

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

Isselbacher, Kurt J., et al. Harrison's Principles of Internal Medicine. New York: McGraw Hill, 1994.

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.

Krugman, Saul, et al. Infectious Diseases of Children. St. Louis: Mosby-Year Book, Inc., 1992.

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

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

Willett, Edward. Meningitis (Diseases and People). Berkeley Heights, NJ: Enslow Publsihers, 1999.

periodicals

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

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

Rosalyn Carson-DeWitt

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.