CHAPTER 117
Infections of the Brain and Spinal Cord
The brain and spinal cord are remarkably resistant to infection, but when they become infected, the consequences are often very serious. Infections may be caused by bacteria, viruses, fungi, or, occasionally, protozoa or parasites. Another group of brain disorders that resemble infections, called spongiform encephalopathies, are caused by prions, which are abnormal protein molecules (see page 765).
Infections usually cause inflammation. For example, infection can cause meningitis, which is inflammation of the space within the layers of tissue (meninges) that cover the brain and spinal cord. This space (the subarachnoid space) contains cerebrospinal fluid, which flows between the meninges and helps cushion the brain and spinal cord. Without treatment, bacterial meningitis spreads to the brain, causing inflammation of brain tissue (encephalitis). Viral infections can also cause encephalitis. Usually, such infections also cause meningitis. Thus, usually when bacterial meningitis or viral encephalitis develops, the resulting disorder is technically meningoencephalitis. However, infection that affects mainly the subarachnoid space and meninges is usually called meningitis, and infection that affects mainly the brain is usually called encephalitis.
In meningitis and encephalitis, inflammation occurs throughout the brain and, in meningitis, throughout the spinal cord. But sometimes infection is confined to one area (localized) as a collection of pus, called an empyema or an abscess depending on where it is located. An abscess, which resembles a boil, can form anywhere in the body, including the brain. Fungi (such as aspergilli), protozoa (such as Toxoplasma gondii), and parasites (such as Taenia solium may cause a localized brain infection similar to an abscess.
Bacteria and other infectious organisms can reach the meninges and other areas of the brain in several ways:
By being carried by the blood
By entering the brain directly from the outside (for example, through a skull fracture or during surgery on the brain)
By spreading from nearby infected structures, such as the sinuses or middle ear
Acute Bacterial Meningitis
Acute bacterial meningitis is rapidly developing inflammation of the subarachnoid space (located within the layers of tissue covering the brain and spinal cord) that is caused by bacteria.
Older children and adults develop a stiff neck, usually with a fever and headache.
Infants and young children may have a high or low body temperature, be irritable or drowsy, or not eat well.
Antibiotics are effective if given promptly.
Usually, a spinal tap is done but typically after treatment is started.
Vaccines can prevent some forms of meningitis.
The subarachnoid space is located between the middle layer (arachnoid mater) and the thin inner layer (pia mater) of tissues (called meninges) that cover the brain and spinal cord (see art on page 624). This space contains the cerebrospinal fluid, which flows through the meninges, fills internal spaces within the brain, and helps cushion the brain and spinal cord.
When bacteria invade the subarachnoid space, the immune system eventually reacts to the invaders, and immune cells gather to defend the body against them. The result is inflammation. Severe inflammation can spread to blood vessels within the brain, sometimes causing clots to form. A stroke can result. Inflammation can also cause widespread damage to brain tissue, causing swelling (edema) and small areas of bleeding. If swelling is severe, it can increase pressure within the skull (intracranial pressure), causing parts of the brain to shift. If these parts are pressed through one of the small natural openings in the tissues that separate the brain into compartments, a life-threatening disorder called brain herniation results.
Bacterial meningitis is most common among infants, children, adolescents, and people over 55. Small epidemics of one particularly dangerous type of meningitis, called meningococcal meningitis, may occur among people living in close quarters, as occurs in military barracks and college dormitories.
Meningitis may also be caused by viruses, fungi, protozoa, cancer cells, certain drugs (which trigger an allergic reaction), and irritating substances (including air and chemicals).
Causes
Different species of bacteria cause meningitis in different settings.
If meningitis is acquired outside of a hospital or nursing home (in the community), it is usually caused by Neisseria meningitides (which causes meningococcal meningitis) or by Streptococcus pneumoniae. Both species are normally present in the external environment. They also reside in the nose and upper respiratory system of some people without causing harm. Occasionally, these organisms infect the brain without an identifiable reason. In other cases, infection develops because the immune system is weakened by a disorder or by a drug that suppresses it (immunosuppressant). The following increase the risk of developing bacterial infections, including meningitis:
Certain chronic disorders that affect the heart, lungs, liver, kidneys, joints, or the endocrine or immune system
Use of corticosteroids or immunosuppressants, which may be used to prevent rejection of an organ transplant or to treat disorders such as cancer and autoimmune disorders
Splenectomy (removal of the spleen)
Chronic infections of the middle ear, nose, or sinuses
Pneumococcal pneumonia
Sickle cell disease
Sometimes meningitis results from a head injury. For example, a skull fracture may create an opening between the nasal sinuses and the subarachnoid space. Bacteria can travel from the sinuses through the opening and infect the meninges.
Meningitis due to Streptococcus pneumoniae (pneumococcal meningitis) is becoming less common because people are now routinely vaccinated against it.
Listeria monocytogenes causes bacterial meningitis in newborns, pregnant women, and people over 50. Having kidney or liver failure or taking corticosteroids or immunosuppressants increases the risk of developing meningitis due to these bacteria.
Meningitis due to Escherichia coli (which normally resides in the colon and in feces) or Klebsiella bacteria usually develops after a widespread infection of the blood (sepsis), an infection acquired in a hospital, or surgery on the brain or spinal cord. People with a weakened immune system are more likely to develop sepsis and infections in a hospital and thus to develop meningitis due to these bacteria.
Meningitis due to Pseudomonas bacteria is more common among people with a weakened immune system.
Meningitis due to Staphylococcus aureus can occur after an injury or a surgical procedure that penetrates the skull or after infection of the heart valves (causing endocarditis) by these bacteria.
Newborns, whose immune system is not completely formed, are at increased risk of developing meningitis due to Escherichia coli or group B streptococci.
Symptoms
In older children and adults, the following symptoms may occur early:
Fever
Headache
Stiff neck (usually)
Vomiting is also common. These symptoms are sometimes preceded by a sore throat, cough, runny nose, or other symptoms suggesting a respiratory illness. The stiff neck is more than just sore. Trying to lower the chin to the chest causes pain and may be impossible. Moving the head in other directions is not as difficult.
In children up to 2 years old, some combination of the following usually occurs first:
High or low body temperature
Feeding problems
Vomiting
Irritability
Seizures
Sluggishness (lethargy)
High-pitched crying
Unlike older children or adults, infants younger than 1 year may not develop a stiff neck (see page 1761).
Adults may become seriously or desperately ill within 24 hours, and children even sooner.
In meningococcal meningitis, a rash (usually red and purple spots) sometimes develops. The rash is most prominent on the trunk and lower extremities. It may be difficult to see at first if people have dark skin.
The bacterial infection causes swelling of brain tissue. In children up to 2 years old, the swelling may make the soft spots between the skull bones (fontanelles) bulge. (These soft spots enable the skull to pass through the birth canal. They harden by about age 2 years.) The swelling may block the flow of cerebrospinal fluid around the brain, causing the fluid to accumulate and put pressure on the brain (a disorder called hydrocephalus). Sometimes a collection of pus (subdural empyema) forms under the outer layer (dura mater) of the meninges.
Older children and adults can become irritable, confused, then increasingly drowsy. Drowsiness can progress to unresponsiveness that requires vigorous stimulation for arousal (stupor), coma, and death. The swelling increases pressure inside the skull and can hamper blood flow, sometimes causing symptoms of stroke, including paralysis. Some people have seizures.
In most people with meningococcal meningitis, the bloodstream and many organs are also infected—a disorder called meningococcemia. Meningococcemia can become severe within hours. As a result, areas of tissue may die, and bleeding may occur under the skin (causing red spots or purple blotches), in mucous membranes, and within the digestive tract and other organs. Without treatment, blood pressure drops, leading to shock and death. Typically, bleeding occurs within the adrenal glands, which shut down, making shock worse. This disorder, called the Waterhouse-Friderichsen syndrome, is often fatal unless treated promptly.
Sometimes meningitis develops while people are being treated for another infection (such as an ear or throat infection). Or early meningitis may be mistaken for another infection and be treated with antibiotics. In either case, the symptoms of meningitis are much milder than normal, making meningitis more difficult to recognize.
COMMON INFECTIONS THAT CAN CAUSE MENINGITIS
| ORGANISM | COMMENTS |
| Bacterial infections | |
| Infection with Escherichia coli | Newborns, older people, and people with a weakened immune system are affected most often. Meningitis due to these bacteria usually develops after a widespread infection of the blood (sepsis), an infection acquired in a hospital, or surgery on the brain or spinal cord. |
| Infection with Klebsiella bacteria | Meningitis due to these bacteria usually develops after sepsis, an infection acquired in a hospital, or surgery on the brain or spinal cord, or in people with a weakened immune system. |
| Infection with Listeria monocytogenes | Newborns, people over 50, pregnant women, people with kidney or liver failure or disorders of the immune system, and people who take drugs that affect the immune system are most often affected. These bacteria may be present in unpasteurized milk products and on many butcher’s meat counters. |
| Infection with Neisseria meningitides | Meningitis due to these bacteria (meningococcal meningitis) is highly contagious and dangerous and causes small epidemics among people living in close quarters. It can cause death within 24 hours. |
| Infection with group B streptococci | Newborns are affected most often. |
| Infection with Streptococcus pneumoniae | Pneumococcal meningitis occurs more often in infants, alcoholics, and people with ear infections. These bacteria also cause pneumococcal pneumonia, which increases the risk of meningitis. |
| Lyme disease | The bacteria that cause Lyme disease are spread by ticks. Lyme disease is common in certain areas of the northeastern United States. Lyme disease can affect the skin, joints, heart, brain, and spinal cord. |
| Rocky Mountain spotted fever | The bacteria that cause this infection are transmitted by ticks. The symptoms resemble those of meningitis, but the infection is not meningitis. |
| Syphilis | If untreated, syphilis can affect the brain, layers of tissue that cover it (meninges), or both several years after the original infection (or much earlier in people who have HIV infection or AIDS). |
| Tuberculosis | Immigrants from areas where tuberculosis is common (such as Asia, Africa, or Latin America), homeless people, and people with HIV infection or AIDS are affected most often. |
| Viral infections | |
| Enteroviral infections | Enteroviruses are commonly present in the digestive tract and may cause infection when hands are not washed adequately after going to the toilet. Spread among family members is common. |
| Herpes simplex virus type 2 infection | This virus causes genital herpes and can cause recurrent episodes of meningitis called Mollaret’s meningitis. |
| Human immunodeficiency virus (HIV) infection | Meningitis can develop days to weeks after the initial infection. |
| Cytomegalovirus infection | In people with HIV infection, this virus can cause a painful meningitis that affects spinal nerves in the lower back. |
| Infectious mononucleosis | Rarely, this infection, caused by the Epstein-Barr virus, spreads to the meninges. |
| Mumps | Mumps is a common cause of meningitis worldwide but not in the United States because children are routinely vaccinated against it. |
| West Nile virus infection | This infection is spread by mosquitoes. |
| Lymphocytic choriomeningitis | Most often, this infection results from exposure to dust or food contaminated by waste products from mice and hamsters. |
| Fungal infections | |
| Cryptococcosis | People with HIV infection, AIDS, or other disorders that weaken the immune system are usually affected. |
| Coccidioidomycosis | This infection occurs mostly in the southwestern United States. |
| AIDS = acquired immunodeficiency syndrome; HIV = human immunodeficiency virus. | |
Diagnosis
If a child 2 years old or younger has an unexplained fever and a parent senses that the child is ill, the parent should see or call a doctor immediately, particularly if symptoms do not resolve after an adequate dose of acetaminophen. Children require immediate medical attention if they do any of the following:
Become increasingly irritable or unusually sleepy
Have a low body temperature
Refuse to eat
Have seizures
Develop a stiff neck
Adults require immediate medical attention if they have any of the following:
Confusion
Stupor
Seizures
Some combination of fever, rash, and a stiff neck
During the physical examination, doctors look for telltale signs of meningitis, such as a stiff neck and skin rash. When doctors suspect rapidly developing meningitis, they withdraw a sample of the person’s blood and send it to a laboratory, where the bacteria can be grown (cultured) overnight. If bacteria are detected, bacterial infection is confirmed. Culture also helps identify which bacteria are causing infection. Culture results can take up to 2 days. At some hospitals, new blood tests can provide the same information within a few hours.
A spinal tap (lumbar puncture—see art on page 635) is done but usually not until after tests, such as computed tomography (CT) of the brain and sometimes blood clotting tests, are done to determine whether a spinal tap is safe. CT of the head is done to check for a mass (such as a hemorrhage, tumor, or abscess), which may increase pressure within the skull. If pressure is increased, the brain may shift downward, causing brain herniation.
During a spinal tap, a thin needle is inserted between two vertebrae in the lower spine to withdraw cerebrospinal fluid. Doctors look closely at the fluid, which is normally clear but is cloudy in meningitis. The fluid’s pressure is measured. Pressure is usually high in meningitis. Sugar and protein levels and the number and type of white blood cells in the fluid are determined. This information helps doctors distinguish between bacterial and viral infections. The fluid is examined under a microscope to check for and identify bacteria. If bacteria are seen, other tests are done to rapidly identify certain bacteria, such as Neisseria meningitidis and Streptococcus pneumoniae. Some of these tests can detect proteins (antigens) on the surface of bacteria and thus identify them. The polymerase chain reaction (PCR) technique, which produces many copies of a gene, may be used to identify the bacteria’s unique DNA sequence.
The cerebrospinal fluid is also cultured, and after 24 hours, the resulting bacteria are tested to determine which antibiotics are effective against them (called susceptibility testing). Then, antibiotic therapy, which was already started, can be adjusted if necessary.
Until the cause of meningitis is confirmed, other tests using cerebrospinal fluid or blood samples may be done to check for viruses, fungi, cancer cells and other substances that routine tests do not identify. Testing for herpes simplex virus, which can infect the brain (causing encephalitis), is particularly important.
Doctors also take samples of blood, urine, and mucus from the nose and throat, and in people who have a rash, they may use a small needle to remove fluid and tissue from under the skin where the rash is. These samples are cultured and examined under the microscope to see whether bacteria are present.
Treatment
Because acute bacterial meningitis can lead to death within hours, treatment is started as soon as possible, without waiting for the results of diagnostic tests and usually before a spinal tap is done. Several antibiotics are given intravenously, often in the emergency department. Doctors choose antibiotics that are effective against the bacteria most likely to be causing the infection. However, because doctors cannot identify the bacteria causing the infection based on symptoms alone, they usually choose several antibiotics that are effective against many organisms. Also, an antiviral drug that is effective against the herpesvirus that causes inflammation of the brain (encephalitis) is given. Once the infecting organism, usually a specific species of bacteria, is identified, the antibiotics are changed to ones that are most effective against that organism, and any unnecessary antibiotics and antiviral drugs are stopped.
A corticosteroid, such as dexamethasone, is given 15 minutes before or at the same time as the first antibiotic dose. The corticosteroid is continued for 2 to 4 days. Corticosteroids are given to suppress inflammation caused by fragments of bacteria, which are produced when antibiotics break bacteria apart. This inflammation causes swelling that can damage the brain. Corticosteroids can also reduce pressure within the skull and, if the adrenal glands are damaged, replace the corticosteroids normally produced by these glands.
Fluids lost because of fever, sweating, vomiting, and poor appetite are replaced. Because bacterial meningitis often affects many organs and causes serious complications, people are usually admitted to the intensive care unit.
Complications may require specific treatment.
Seizures: Anticonvulsants are given (see table on page 716).
Shock: Additional fluids and sometimes drugs (given intravenously) are given to increase blood pressure and treat shock (see page 350), as can occur in the Waterhouse-Friderichsen syndrome.
Coma: Mechanical ventilation is used.
Dangerously increased pressure within the skull: Mechanical ventilation is used to decrease the amount of carbon dioxide in the blood and thus quickly but briefly reduce pressure in the cerebrospinal fluid. Then mannitol or a similar drug is given intravenously. Mannitol causes water in the brain to move into the bloodstream and thus reduces cerebrospinal fluid pressure within the skull. Pressure within the skull may be monitored with a gauge or a small tube (catheter) connected to a gauge. The device is inserted through a tiny opening drilled through the skull. The catheter can also be used to remove cerebrospinal fluid and thus reduce pressure when necessary.
Subdural empyema: A surgeon may have to drain an empyema with a needle to ensure a successful recovery.
Prognosis
If treated early, most people recover well. But when treatment is delayed, permanent brain damage or death is more likely, especially in very young children and older people. In some people, seizures require lifelong treatment. Neurologic problems, such as permanent mental impairment, paralysis, and hearing loss, may also result.
Prevention
People with acute meningitis (particularly meningococcal meningitis) are usually placed in isolation until the infection is controlled and they can no longer spread the infection, usually for a few days or less. Vaccines for several forms of meningitis are available.
Meningococcal Meningitis: A vaccine can help prevent this type of meningitis. It is given to children 2 years old or older whose immune system is weakened. It is also recommended for the following people:
Adolescents
Students living in dormitories
Military recruits
People who may be repeatedly exposed to the bacteria
The vaccine is also used when an epidemic occurs or when there is a threat of an epidemic in a self-contained group of people (such as those living in military barracks). Family members, medical personnel, and others in close contact with people who have meningococcal meningitis should be given an antibiotic (such as rifampin or ciprofloxacin taken by mouth or ceftriaxone given by injection) as a preventive measure.
Meningitis Due to Streptococcus pneumoniae: A vaccine that helps protect against this infection is now routinely given to children.
SOME NONINFECTIOUS CAUSES OF MENINGITIS
| TYPE | EXAMPLES |
| Brain disorders | Cancer that has spread to the brain from other parts of the body (such as leukemia, lymphoma, melanoma, and breast or lung cancer) Sarcoidosis Behçet’s syndrome Craniopharyngioma |
| Drugs that affect the immune system | Azathioprine Cyclosporine Cytosine arabinoside Intravenous immune globulin OKT3 Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, naproxen, sulindac, and tolmetin |
| Other drugs | Antibiotics (such as ciprofloxacin, isoniazid, penicillin, trimethoprim-sulfamethoxazole, and other sulfa drugs) Carbamazepine Phenazopyridine Ranitidine |
| Substances injected into the subarachnoid space* | Antibiotics Chemotherapy Dyes used in imaging procedures Anesthetics |
| Vaccines | Pertussis (whooping cough) Rabies Smallpox |
| * The space that contains cerebrospinal fluid and is located between layers of tissue covering the brain and spinal cord (meninges). | |
Meningitis Due to Haemophilus influenzae: Children are now routinely immunized with Haemophilus influenzae type b vaccine, which has virtually eliminated what once was the most common cause of meningitis in children.
Chronic Meningitis
Chronic meningitis is a slowly developing inflammation of the subarachnoid space (located within the layers of tissues covering the brain and spinal cord) that lasts a month or longer.
People may have a fever, a stiff neck, a headache, double vision, or difficulty walking, or they may become confused.
Imaging of the head and a spinal tap are required for diagnosis.
Treatment depends on the cause.
The subarachnoid space is located between the middle layer (arachnoid mater) and the thin inner layer (pia mater) of the tissues that cover the brain and spinal cord (meninges—see art on page 624).
Chronic meningitis resembles acute bacterial meningitis, but the causes are different and the infection and inflammation develop more slowly, over weeks and months rather than hours and days. If symptoms have been present for a month or more, meningitis is described as chronic.
Causes
Chronic meningitis is usually due to infection, most commonly tuberculosis.
Infectious organisms invade the brain or the subarachnoid space and multiply slowly over weeks or months. Such organisms include the bacteria that cause tuberculosis or syphilis and fungi such as Cryptococcus neoformans or Coccidioides immitis. These fungi are more likely to cause chronic meningitis in people with a weakened immune system, such as those with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
Acute bacterial meningitis that has been partially treated but not eliminated by antibiotics may evolve into chronic meningitis.
Disorders that are not infections can also cause chronic meningitis. They include sarcoidosis and certain cancers, such as leukemia, lymphoma, brain tumors, and some cancers that spread (metastasize) to the brain from other parts of the body (such as breast or lung cancer).
Chemotherapy drugs that are injected directly into the subarachnoid space (such as methotrexate), drugs used to prevent rejection of a transplanted organ (such as cyclosporine and OKT3), and even nonsteroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen—see page 644) can cause mild to moderate meningitis that lasts days to a few weeks. If treatments are repeated, the meningitis may last longer.
Symptoms
The symptoms of chronic meningitis are similar to those of acute bacterial meningitis, except that they develop more slowly and gradually, usually over weeks rather than days. Also, fever is often less severe.
Headache, confusion, a stiff neck, and backache are common. People may have difficulty walking. Weakness, pins-and-needles sensations, numbness, facial paralysis, and double vision are also common. Facial paralysis and double vision occur when meningitis affects the cranial nerves (which go directly from the brain to various parts of the head, neck, and trunk).
Diagnosis
Computed tomography (CT) or magnetic resonance imaging (MRI) of the head, followed by a spinal tap (lumbar puncture) with examination of the cerebrospinal fluid, can confirm the diagnosis.
By examining the cerebrospinal fluid, doctors can distinguish between chronic and acute meningitis. In chronic meningitis, the number of white blood cells in the fluid is higher than normal but is usually lower than that in acute bacterial meningitis. Also, the type of white cells is usually different. Some infectious organisms that cause chronic meningitis, such as the fungus Cryptococcus neoformans, are readily visible under a microscope, but many, such as the bacteria that cause tuberculosis, are not.
The cerebrospinal fluid is always sent to a laboratory, where the organism, if present, can be grown (cultured) and identified. However, culturing may take weeks. Special techniques, which may provide results more quickly, may be used to identify fungi and the bacteria that cause tuberculosis and syphilis. For example, the polymerase chain reaction (PCR) technique, which produces many copies of a gene, may identify the unique DNA sequence of the bacteria that cause tuberculosis.
Other tests on cerebrospinal fluid are done, depending on which disorders are suspected. For example, the fluid may be analyzed for cancer cells if metastatic cancer is suspected.
Treatment
The cause of meningitis is treated. For example, chronic meningitis due to sarcoidosis is usually treated with corticosteroids (such as prednisone) for several weeks. Chronic meningitis due to cancer is treated with chemotherapy, radiation therapy, or both. The chemotherapy drug is injected directly into the subarachnoid space through an Ommaya reservoir. This device is implanted under the scalp and delivers the drug slowly, over days or weeks, through a small tube to the spaces around the brain.
Treatment of chronic meningitis due to an infection depends on the organism. Chronic meningitis due to a fungus is usually treated with antifungal drugs given intravenously or by mouth. Amphotericin B, flucytosine, and fluconazole are used most often. When the infection is particularly difficult to cure, amphotericin B is sometimes injected directly into the cerebrospinal fluid, either by repeated spinal taps or through an Ommaya reservoir. When chronic meningitis is due to Cryptococcus neoformans amphotericin B is usually combined with flucytosine.
Aseptic Meningitis
Aseptic meningitis is inflammation of the subarachnoid space (located within the layers of tissue covering the brain and spinal cord) that is diagnosed when standard testing does not detect bacteria.
Viruses, often those frequently present in the digestive tract, are the most common cause.
Headache, stiff neck, fever, and nausea may develop over days.
A spinal tap is done, and if standard tests of cerebrospinal fluid detect inflammation but no bacteria that could cause it, aseptic meningitis is diagnosed.
Acetaminophen and fluids can relieve symptoms, but otherwise treatment depends on the cause.
In aseptic meningitis, the space between middle and inner layers of tissues covering the brain and spinal cord (meninges) is inflamed. This space, called the subarachnoid space, forms a channel for cerebrospinal fluid, which flows over the surface of the brain and spinal cord (see art on page 624).
Causes
Aseptic meningitis is usually caused by a virus but occasionally has another cause. Unless comprehensive testing is done, the cause is often unidentified.
Viruses: Some viruses can directly infect the meninges and subarachnoid space around the brain and suddenly cause meningitis. Among the most common are
Enteroviruses (which are often present in the digestive tract), such as echovirus and coxsackievirus
Mosquito-borne viruses (usually West Nile virus)
Infections caused by these viruses can occur in epidemics.
Other viruses directly cause infection that occurs as isolated cases (sporadically). They include the herpes simplex virus, Epstein-Barr virus, human immunodeficiency virus (HIV), varicella-zoster virus (that causes chickenpox), and mumps virus. Mumps is a common cause of meningitis worldwide, but it is uncommon in the United States because vaccination is widespread. In Mollaret’s meningitis, aseptic meningitis occurs repeatedly. It is caused by herpes simplex virus type 2, which causes most cases of genital herpes. Viruses that cause encephalitis usually also cause some degree of meningitis.
Bacteria: Sometimes aseptic meningitis is diagnosed when meningitis is caused by bacteria that are hard to identify, such as the bacteria that cause Lyme disease, syphilis, or tuberculosis.
Other Conditions: Aseptic meningitis may be caused by the following (see table on page 755):
Fungi
Certain noninfectious disorders
Certain drugs, particularly drugs that affect the immune system
Reactions to certain vaccines, such as those for pertussis (whooping cough) or rabies
Injection of drugs or dyes (for treatment or diagnosis) in the subarachnoid space
Symptoms
Meningitis often develops after or at the same time as a flu-like illness or viral infection that causes mild symptoms. These symptoms are often general and may include fever, a general feeling of illness (malaise), cough, muscle aches, and headache.
Usually, aseptic meningitis causes symptoms that are similar to those of bacterial meningitis (fever, headache, vomiting, sluggishness, and a stiff neck). However, people do not become as ill. People may not have a fever, particularly when the cause is not an infection.
Most people recover in 1 to 2 weeks.
Diagnosis
When meningitis is suspected, a spinal tap (lumbar puncture) is usually done to obtain a sample of cerebrospinal fluid, and standard tests are done on the fluid. They include determining the number and type of white blood cells in the fluid and growing (culturing) bacteria in the fluid so that they can be identified (see page 753). Doctors diagnose aseptic meningitis when the cerebrospinal fluid contains excess white blood cells (indicating inflammation) but standard tests do not detect any bacteria that could be the cause.
Usually, standard tests do not include culturing viruses, which is technically difficult and may take many days. (An exception is enteroviruses, which can be cultured.) Instead, the polymerase chain reaction (PCR) technique is used to identify viruses (such as herpesviruses and HIV) and to measure levels of antibodies to the virus in cerebrospinal fluid and blood. Antibody levels are measured initially and 3 to 4 weeks later. Then the measurements are compared. If antibody levels increase much more in the cerebrospinal fluid than in the blood, the virus probably caused the meningitis. If the increase in cerebrospinal fluid and blood is about as same, the virus probably infected the body but did not cause the meningitis.
Treatment
The cause, if identified, is treated. For example, if the bacteria that cause Lyme disease, syphilis, or tuberculosis are identified, antibiotics specific for those bacteria are used. Cancer is treated with surgery, radiation therapy, or chemotherapy, as appropriate. If a drug is the cause, it is stopped or the dose is reduced. Most viral infections are not treated with antiviral drugs and resolve on their own. However, Mollaret’s meningitis is treated with acyclovir, and cytomegalovirus infection is treated with ganciclovir.
If doctors suspect aseptic meningitis but cannot rule out bacterial meningitis at the initial examination, several antibiotics are given as if bacterial meningitis were the diagnosis. Doctors do not wait for test results. If tests do not detect any bacteria in the cerebrospinal fluid and if the fluid contains levels of sugar, protein, and white blood cells that suggest aseptic meningitis, antibiotics are stopped.
Regardless of the cause, symptoms are treated. Acetaminophen, given by mouth, and fluids, given by mouth or intravenous injection, can relieve headache and fever.
Rabies
Rabies is a viral infection of the brain that is transmitted by animals and that causes inflammation of the brain and spinal cord. Once the virus reaches the spinal cord and brain, rabies is fatal.
The virus can be transmitted when people are bitten by an infected animal, usually a wild animal.
Rabies can cause restlessness and confusion or paralysis.
A skin biopsy can detect the virus.
Infection can be prevented by immediately cleaning the wound and by injecting rabies vaccine and immune globulin.
From the point of entry (usually a bite), the rabies virus travels along nerves to the spinal cord and then to the brain, where it multiplies. From there, it travels along other nerves to the salivary glands and into the saliva. Once the rabies virus reaches the spinal cord and brain, rabies is fatal. However, the virus takes at least 10 days—usually 30 to 50 days—to reach the brain (how long depends on the bite’s location). During that interval, measures can be taken to stop the virus and help prevent death.
Rabies causes an estimated 55,000 deaths worldwide each year. Most deaths occur in rural areas of Asia and Africa. In the United States, only a few people die each year.
Causes
The rabies virus is present in many species of wild and domestic animals throughout most of the world. Animals with rabies may be sick for several weeks before they die. During that time, they often spread the disease.
The rabies virus, which is present in the saliva of a rabid animal, is transmitted when the animal bites or, very rarely, licks another animal or a person. The virus cannot pass through intact skin. It can enter the body only through a puncture or another break in the skin or through the nose or mouth when many airborne droplets containing the virus are inhaled (as can occur in a cave that contains infected bats).
Many different mammals—such as dogs, cats, bats, raccoons, skunks, and foxes—can transmit rabies to people. Rabies rarely affects rodents (such as hamsters, guinea pigs, gerbils, squirrels, chipmunks, rats, and mice), rabbits, or hares. In the United States, these animals have not been known to cause rabies among people. Rabies does not affect birds and reptiles.
In the United States, vaccination has largely eliminated rabies in dogs, and the source of rabies is almost always wild animals, usually bats. In many cases, the bat bites are unnoticed. Most deaths due to rabies result from being bitten by an infected bat.
Worldwide, during the last 30 years, most people who have contracted rabies were bitten by rabid wild animals. In most countries of Latin America, Africa, Asia, and the Middle East (where vaccination of dogs is not widespread), rabies in dogs is fairly common, and dogs are responsible for most deaths due to rabies.
Symptoms
The wound from the bite may be painful or numb. Bat bites typically cause no symptoms.
Symptoms appear when the rabies virus reaches the brain or spinal cord, usually 30 to 50 days after a person is bitten. However, this interval can vary from 10 days to more than a year. The closer the bite to the brain (for example, on the face), the more quickly symptoms appear.
Rabies may begin with a fever, headache, and a general feeling of illness (malaise). Most people become restless, confused, and uncontrollably excited. Their behavior may be bizarre. They may hallucinate and have insomnia. Saliva production greatly increases. Spasms of the muscles in the throat and larynx occur because rabies affects the area in the brain that controls swallowing, speaking, and breathing. The spasms can be excruciatingly painful. A slight breeze or an attempt to drink water can trigger the spasms. Thus, people with rabies cannot drink. For this reason, the disease is sometimes called hydrophobia (fear of water).
As the disease spreads through the brain, people become more confused and agitated. Eventually, coma and death result. The cause of death can be blockage of airways, seizures, exhaustion, or widespread paralysis.
Did You Know…
In the United States, people who are bitten by rabbits and most small rodents—such as hamsters, gerbils, squirrels, rats, and mice—almost never need a rabies vaccination.
Bats are responsible for most deaths due to rabies in the United States.
In 20% of people, rabies begins with paralysis of the limb that was bitten. The paralysis then moves through the body. In these people, thinking is typically unaffected, and most of the other symptoms of rabies do not develop.
Diagnosis
Doctors suspect rabies when people have a headache, confusion, and other symptoms of the disease, especially if people have been bitten by an animal or exposed to bats (for example, if they were exploring a cave). However, many people with rabies are unaware of having been bitten by an animal or exposed to bats. A sample of skin is taken (usually from the neck) and examined under a microscope (skin biopsy) to determine whether the virus is present. Samples of saliva and urine are also examined to check for the virus. A spinal tap (lumbar puncture) is done to obtain a sample of cerebrospinal fluid, which is also examined. A variation of the polymerase chain reaction (PCR) technique, which produces many copies of a gene, is often used to identify the bacteria’s unique DNA sequence. Several samples of these fluids, taken at different times, are tested to increase the chances of detecting the virus.
Who Should Receive the Rabies Vaccine?
In the United States, the decision to give the rabies vaccine to a person who has been bitten by an animal depends on the type and status of the animal.
For people bitten by a pet dog, cat, or ferret: If the animal appears healthy and can be observed for 10 days, the vaccine is not given unless the animal develops symptoms of rabies. If the animal develops any symptom suggesting rabies, people are given vaccine immediately. Animals that develop symptoms of rabies are put to sleep (euthanized), and their brain is examined for the rabies virus. If the animal is still healthy after 10 days, it did not have rabies at the time of the bite, and vaccine is not needed.
If an animal has or appears to have rabies, the vaccine is given immediately.
If the status of an animal cannot be determined—for example, because it escaped—public health officials are consulted to determine how likely rabies is and whether the vaccine should be given.
For people bitten by skunks, raccoons, foxes, most other carnivores, or bats: Such an animal is considered rabid unless it can be tested and the results are negative. Usually, the vaccine is given immediately. Waiting to observe wild animals for 10 days is not recommended.
Because people may not notice a bat bite, they are given the vaccine if a bite seems possible. For example, if someone awakens and a bat is in the room, the vaccine is given.
For people bitten by livestock, small rodents, large rodents (such as woodchucks and beavers), rabbits, or hares: Each biting incident is considered individually, and public health officials are consulted. People who are bitten by hamsters, guinea pigs, gerbils, squirrels, chipmunks, rats, mice, other small rodents, rabbits, or hares almost never require rabies vaccination.
Treatment
After symptoms develop, no treatment can help. The infection is virtually always fatal. Treatment involves relieving symptoms and making people as comfortable as possible.
Prevention
Before an Animal Bite: Avoiding being bitten by animals, especially wild animals, is best. Pets that are not known and wild animals should not be approached. Signs of rabies in wild animals may be subtle, but their behavior is typically abnormal, as in the following:
Wild animals may not appear vicious, shy, or afraid when people approach them.
Nocturnal animals (such as bats, skunks, raccoons, and foxes) are out during the day.
Bats make unusual noises or have difficulty flying.
Animals bite without being provoked.
Animals are weak or agitated and vicious.
An animal that may be rabid should not be picked up to try to help it. A sick animal often bites. If an animal appears sick, people should call local health authorities, who can help remove it.
People who are likely to be exposed to the rabies virus should be given an injection of the rabies vaccine before exposure. Such people include veterinarians, laboratory workers who handle animals that may be rabid, people who live or stay more than 30 days in developing countries where rabies in dogs is widespread, and people who explore bat caves. Vaccination protects most people to some degree for the rest of their life. However, protection decreases with time, and if exposure is likely to continue, people should get a booster dose of vaccine every 2 years.
After an Animal Bite: Immediately after being bitten, people should clean the wound thoroughly with soap and water. Deep puncture wounds are flushed out with running water. Then people should see a doctor. Doctors clean the wound further with an antiseptic called benzalkonium chloride. They may trim ragged edges of the wound.
Doctors also try to determine the likelihood that rabies was transmitted. Early determination is essential because rabies can usually be prevented if appropriate measures are taken promptly.
No test can determine whether the rabies virus has been transmitted immediately after an animal bite. Thus, people who have been bitten may be given immune globulin and vaccine by injection to prevent rabies. Rabies immune globulin, which consists of antibodies to the virus, provides protection immediately but only for a short time. The rabies vaccine stimulates the body to produce antibodies to the virus. The vaccine provides protection that begins more gradually but that lasts for a much longer time.
Whether vaccine and immune globulin are needed depends on whether people have been previously immunized with rabies vaccine and what the type and status of animal are. For example, doctors determine the following:
Whether the animal was a dog, a raccoon, or something else
Whether it appeared sick
Whether the attack was provoked
Whether the animal is available for observation
If people need preventive treatment and have not been immunized previously, they are given rabies immune globulin and rabies vaccine right away (on day 0). Immune globulin is injected around the wound if possible. They are given four more injections of the vaccine on days 3, 7, 14, and 28. The injection site may be painful and swollen but usually only slightly. Serious allergic reactions are rare.
If people have already been vaccinated, the risk of developing rabies is reduced. However, the wound must be cleaned promptly, and an injection of rabies vaccine is given immediately and on day 3.
Encephalitis
Encephalitis is inflammation of the brain that occurs when a virus directly infects the brain or when a virus or something else triggers inflammation. The spinal cord may also be involved, resulting in a disorder called encephalomyelitis.
People may have a fever, headache, or seizures, and they may feel sleepy, numb, or confused.
Magnetic resonance imaging of the head and a spinal tap are usually done.
Treatment involves relieving symptoms and sometimes using antiviral drugs.
Encephalitis can occur in the following ways:
A virus directly infects the brain.
A virus that caused an infection in the past becomes reactivated and directly damages the brain.
A virus or vaccine triggers a reaction that makes the immune system attack brain tissue (an autoimmune reaction).
Infections that can directly lead to encephalitis can occur in epidemics or occasionally as isolated cases (sporadically).
Epidemic Encephalitis: In the United States, the most common types of epidemic encephalitis are caused by arboviruses. Arboviruses are viruses transmitted to people through the bites of arthropods, usually mosquitoes, fleas, or ticks. (Arbovirus is short for arthropod-borne virus.) The viruses are transmitted to arthropods when arthropods bite infected animals. Many species of domestic animals and birds carry these viruses.
Epidemics occur in people only periodically—when the population of mosquitoes or infected animals increases. They tend to occur when arthropods are biting—for mosquitoes and ticks, usually during warm weather. Infection spreads from arthropod to person, not from person to person.
Many arboviruses can cause encephalitis. The different types of encephalitis that result are usually named for the place the virus was discovered or the animal species that typically carries it.
In the United States, mosquitoes spread several types of encephalitis, including the following:
La Crosse encephalitis is caused by the La Crosse virus (also called California virus). It is most common in the Midwest but can occur anywhere in the country. This encephalitis accounts for most cases in children. Many cases are mild and undiagnosed. Fewer than 1% of infected people die from it.
Eastern equine encephalitis occurs predominantly in the eastern United States. It affects mainly young children and people older than 55. In children younger than 1 year, it can cause severe symptoms and permanent nerve or brain damage. Over half of infected people die.
West Nile encephalitis, once present only in Europe and Africa, first appeared in the New York City area in 1999. It has spread throughout the United States. Several species of birds are the host for the virus. This encephalitis affects mainly older people. West Nile encephalitis develops in less than 1% of people who develop West Nile fever. About 10% of people with West Nile encephalitis die; however, those who have just West Nile fever usually recover fully.
St. Louis encephalitis occurs throughout the United States but particularly in the Southeast (including Florida), Texas, and some Midwestern states. Epidemics once occurred about every 10 years but are now rare.
Western equine encephalitis can occur throughout the United States but, for unknown reasons, has largely disappeared since 1988. It can affect all age groups but mainly children younger than 1 year.
In other parts of the world, encephalitis is caused by different but related arboviruses. Examples are Venezuelan equine encephalitis and Japanese encephalitis, both spread by mosquitoes.
Sporadic Encephalitis: In the United States, sporadic encephalitis is usually caused by herpes simplex virus type 1. Herpes simplex virus causes up to one third of cases of encephalitis. It occurs at any time of the year and is fatal if not treated. Human immunodeficiency virus (HIV) causes a slowly developing brain infection, resulting in HIV-associated encephalopathy (also called HIV-associated or AIDS dementia).
Reactivation of a Previous Infection: Encephalitis can result from reactivation of herpes simplex virus type 1, varicella zoster virus (which causes chicken-pox), or the virus that causes measles (which leads to a usually fatal disorder called subacute sclerosing panencephalitis years after measles occurs). After reactivated infection, brain damage can be severe.
Autoimmune Encephalitis: After certain infections or vaccines, the body’s immune system sometimes attacks the layers of tissue that wrap around nerve fibers (called the myelin sheath) in the brain and spinal cord The attack occurs because proteins in myelin resemble those in the virus. As a result, nerve transmission becomes very slow. The resulting disorder, called acute disseminated encephalomyelitis, resembles multiple sclerosis except that symptoms do not come and go as they do in multiple sclerosis. The viruses most often involved include Epstein-Barr virus, cytomegalovirus, and herpes simplex virus.
Symptoms
Before symptoms of encephalitis start, people may have digestive symptoms, such as nausea, vomiting, diarrhea, or abdominal pain. Or they may feel as if they are getting a cold or the flu and have cough, fever, a sore throat, a runny nose, swollen lymph nodes, and muscle aches.
Symptoms of encephalitis include
Fever
Headache
Personality changes or confusion
Seizures
Paralysis or numbness
Sleepiness that can progress to coma and death
People may vomit and have a stiff neck, but these symptoms tend to be less common and less severe than when caused by meningitis.
Encephalitis due to the herpes simplex virus causes headache, fever, and flu-like symptoms at first. People also have seizures, sometimes accompanied by strange smells, vivid flashbacks, or sudden, intense emotions. As the encephalitis progresses, people become confused, have difficulty speaking and remembering, have repeated seizures, then lapse into coma.
HIV-associated encephalopathy can cause gradual personality changes, problems with coordination, and dementia.
If the spinal cord is affected, parts of the body may feel numb and weak. Which parts are affected depend on which parts of the spinal cord are affected (see art on page 794). People may have difficulty controlling bladder and bowel function. If the infection is severe, people may lose sensation, become paralyzed, and lose control of the bladder and bowels.
Did You Know…
Long after a case of measles or chickenpox, the virus can be reactivated and cause inflammation in the brain.
Diagnosis
Doctors suspect encephalitis based on symptoms, especially if an epidemic is in progress. Magnetic resonance imaging (MRI) can detect typical abnormalities in the brain, confirming encephalitis. If MRI is not available, computed tomography (CT) may be done. It can help doctors exclude disorders that can cause similar symptoms (such as stroke and brain tumor) and check for disorders that can make doing a spinal tap dangerous.
A spinal tap (lumbar puncture) is done to obtain a sample of cerebrospinal fluid. Usually, the spinal fluid contains white blood cells, red blood cells, or both. To identify the virus causing encephalitis, doctors take samples of blood and cerebrospinal fluid and test them for antibodies to the virus when the person is sick and later when the person is convalescing. If the increase in antibodies in cerebrospinal fluid is greater than the increase in the blood, the diagnosis is confirmed. Sometimes techniques are used to grow (culture) viruses in the cerebrospinal fluid so that they can be identified more easily. Enteroviruses can be cultured, but most other viruses cannot.
If doctors suspect that herpes simplex infection is the cause, the polymerase chain reaction (PCR) technique is usually used to identify the virus. PCR can detect the genetic material of the herpes simplex virus. Prompt identification of this virus is essential because the encephalitis it causes is serious and can be fatal. Rarely, a sample of brain tissue is removed and examined under a microscope (biopsy) to determine whether herpes simplex virus or another organism is the cause.
Treatment
If herpes simplex virus cannot be excluded, the antiviral drug acyclovir is given. Acyclovir is effective against herpes simplex and herpes zoster viruses. Usually, several antibiotics are also given in case the cause is bacteria. Cytomegalovirus encephalitis can be treated with ganciclovir.
For HIV-associated encephalopathy, a combination of drugs (see page 1261) helps the immune system function better and delays the progression of the infection and its complications, including dementia.
For other viruses and most other causes, no specific treatment is available. Treatment usually involves relieving symptoms and, when necessary, providing life support until the infection subsides—in about 1 to 2 weeks.
Lymphocytic Choriomeningitis
Lymphocytic choriomeningitis is a flu-like disorder caused by an arenavirus and often followed by meningitis. It occurs when the tissues covering the brain and spinal cord become inflamed.
Rodents can transmit the virus to people through contaminated dust or food.
The infection may cause no symptoms, a flu-like illness, or meningitis.
If symptoms suggest meningitis, a spinal tap is done.
Treatment aims to relieve symptoms.
Most people recover completely.
The arenavirus that causes lymphocytic choriomeningitis is commonly present in rodents, especially gray house mice and hamsters. These animals are usually infected by the virus for life and excrete it in urine, feces, semen, and nasal secretions. Most often, exposure to dust or food contaminated by these waste products causes the disorder in people. The disorder usually occurs in autumn and winter when wild rodents seek shelter indoors.
Symptoms
Most people have no symptoms or very mild symptoms. Symptoms, if they develop, often occur in two phases.
First, flu-like symptoms develop 5 to 10 days after exposure to the virus. Typically, people have a fever of about 101 to 104° F (38.3 to 40° C), sometimes accompanied by shaking. People may feel generally ill (malaise), nauseated, light-headed, and weak. They may have muscle pains, a headache behind the eyes worsened by bright light, and a poor appetite. The throat may become sore. After 5 days to 3 weeks, the flu-like symptoms may subside for 1 or 2 days.
In the second phase, flu-like symptoms recur and other symptoms develop. Knuckle and finger joints may become painful and swollen, and the testes may become inflamed, swollen, and painful. People may lose their hair or vomit. Meningitis may develop, causing a headache and stiff neck, but it tends to be less severe than in acute bacterial meningitis.
Most people who develop meningitis recover completely. However, headaches and fever may recur periodically for months.
Diagnosis
At first, the disorder appears to be the flu, so usually no tests are done.
If symptoms suggest meningitis, a spinal tap (lumbar puncture) is done to obtain a sample of the cerebrospinal fluid. If lymphocytic choriomeningitis is present, the cerebrospinal fluid usually contains many white blood cells, mostly lymphocytes. A sample of blood is also obtained.
The disorder is diagnosed by identifying the virus or by detecting antibodies to the virus in blood or cerebrospinal fluid.
Treatment
No specific treatment is available. Doctors try to relieve the symptoms until the disorder subsides—in about 1 to 2 weeks.
Progressive Multifocal Leukoencephalopathy
Progressive multifocal leukoencephalopathy is a rare infection of the brain that is caused by the JC virus.
People with a weakened immune system are most likely to get the disorder.
People may become clumsy, have trouble speaking, and become partially blind, while mental function declines rapidly.
Death usually occurs within 9 months.
Imaging of the head and a spinal tap are done.
Treating the disorder that weakened the immune system may help.
Progressive multifocal leukoencephalopathy results from infection by the JC virus (which is not related to Creutzfeldt-Jakob disease). The JC virus is often acquired during childhood. Most adults have been infected with the JC virus but do not develop the disorder. The virus appears to remain inactive until something (such as a weakened immune system) allows it to be reactivated and start to multiply. Thus, the disorder affects mainly people whose immune system has been weakened by a disorder, such as leukemia, lymphoma, or acquired immunodeficiency syndrome (AIDS), or by drugs that suppress the immune system (immunosuppressants). Such drugs may be used to prevent rejection of transplanted organs or to treat autoimmune disorders, such as systemic lupus erythematosus (lupus) or multiple sclerosis.
Symptoms
The JC virus appears to cause no symptoms until it is activated.
Symptoms may begin gradually, but they usually worsen rapidly. They vary depending on which part of the brain is infected. In about two of three people, mental function declines rapidly and progressively, causing dementia. Speaking becomes increasingly difficult. People may become partially blind. Walking may become difficult. Rarely, headaches and seizures occur. Death is common within 1 to 9 months of when symptoms start, but a few people survive longer (about 2 years).
Diagnosis
Progressively worsening symptoms in people with a weakened immune system suggest the diagnosis. Magnetic resonance imaging (MRI) of the head is done. It can usually detect abnormalities that suggest the diagnosis.
A spinal tap (lumbar puncture) is done to obtain a sample of cerebrospinal fluid. The polymerase chain reaction (PCR) technique can detect the JC virus in the cerebrospinal fluid. Sometimes the diagnosis is not confirmed until after people have died, when brain tissue can be examined.
Treatment
No treatment has proved effective. However, if the disorder that has weakened the immune system is treated, people survive longer. For example, if the cause is AIDS, highly active antiretroviral therapy is used.
If people are taking immunosuppressants, stopping the drugs may cause progressive multifocal leukoencephalopathy to subside.
Abscess of the Brain
A brain abscess is a localized collection of pus in the brain.
An abscess may form in the brain when bacteria from an infection elsewhere in the head or in the bloodstream or from a wound enter the brain.
Headache, sleepiness, nausea, weakness on one side of the body, or seizures may result.
Imaging of the head is required.
Antibiotics are given, sometimes followed by surgery.
Brain abscesses are fairly uncommon. They can result from an infection that spreads from somewhere else in the head (such as a tooth, the nose, or an ear) or that spreads from another part of the body through the bloodstream to the brain. An abscess may form when bacteria enter after a head wound that penetrates the brain, including those that occur during brain surgery.
Many types of bacteria, including Staphylococcus aureus and Bacteroides fragilis can cause a brain abscess. Toxoplasma gondii (see page 1225), a protozoan, and fungi, such as aspergilli, are common causes of brain abscess in people who have a weakened immune system. The immune system may be weakened by disorders such as human immunodeficiency virus (HIV) infection, which leads to acquired immunodeficiency syndrome (AIDS), or by drugs that suppress the immune system. Such drugs may be used to prevent rejection of a transplanted organ or to treat cancer or autoimmune disorders.
Fluid collects around a brain abscess. As a result, the surrounding brain tissue swells, and pressure within the skull increases. The larger the abscess, the greater the swelling and the pressure. If the abscess leaks or breaks and the pus enters the cerebrospinal fluid, acute meningitis results.
Symptoms
A brain abscess can cause many different symptoms, depending on its location, its size, and the extent of inflammation and swelling around the abscess. People may have a headache, feel nauseated, vomit, become unusually drowsy, and then lapse into coma (which is often occurs when pressure within the brain continues to increase). Seizures may occur, one side of the body may become weak, or thinking may be impaired. Symptoms can develop over days or weeks. A fever and chills may occur at first but then disappear.
Diagnosis
The best test for diagnosing a suspected brain abscess is magnetic resonance imaging (MRI) that uses a substance called gadolinium. Gadolinium, a paramagnetic contrast agent that is injected intravenously, shows up in injured brain regions that have lost their blood-brain barrier—in other words, lost their ability to be highly selective in what molecules are permitted entry from blood into the brain. (Gadolinium is not harmful.) Alternatively, computed tomography (CT) that uses a dye visible on x-rays (radiopaque dye) can be done. MRI has higher resolution and can show early abnormalities better than CT. However, additional tests may be needed to establish the diagnosis because a brain tumor or damage due to a stroke can resemble an abscess. A specialized form of MRI, called magnetic resonance spectroscopy, can distinguish between an abscess (which contains dead or dying tissue) and a tumor (which contains living rapidly duplicating cells).
To identify the causative organism, doctors withdraw a sample of pus from the abscess with a needle. It is examined under a microscope and sent to a laboratory to grow (culture) bacteria in the fluid so that they can be identified. MRI or CT is used to guide the needle into the abscess. For this procedure (called stereotactic aspiration or biopsy), a frame is attached to the skull. The frame provides reference points that can be identified on the MRI or CT scan and enable doctors to guide the needle precisely into the abscess.
Treatment
A brain abscess is fatal unless treated with antibiotics and possibly surgery. The most commonly used antibiotics are cephalosporins (such as cefotaxime or ceftriaxone), vancomycin or nafcillin, and metronidazole. An antibiotic is usually given for 4 to 6 weeks, and MRI or CT is repeated every 2 weeks to monitor the response to treatment. If the abscess does not shrink, a surgeon may have to drain the abscess with a needle (using stereotactic techniques to guide placement of the needle) or perform open surgery to remove the entire abscess. Recovery may be quick or slow depending on how successful surgery is, how many abscesses are present, and how well the person’s immune system is functioning. If people with a weakened immune system have an abscess due to Toxoplasma gondii or a fungus, they must take antibiotics for the rest of their life.
Doctors treat the swelling and increased pressure within the skull aggressively because these effects can permanently damage the brain. Corticosteroids, such as dexamethasone, and other drugs that reduce swelling and pressure (such as mannitol) may be used.
Anticonvulsants may be given to prevent seizures.
Subdural Empyema
A subdural empyema is a collection of pus that develops under the top layer of tissue (dura mater) covering the brain, rather than in the brain itself.
A subdural empyema develops between the outer (dura mater) and middle (arachnoid mater) layers of the tissues that cover the brain (meninges).
A subdural empyema may result from a sinus infection, a severe ear infection, a head injury, surgery involving the head, or a blood infection. The same kinds of bacteria that cause brain abscesses can cause subdural empyemas. In children younger than 5 years, meningitis often accompanies a subdural empyema.
Like a brain abscess, a subdural empyema can cause headache, sleepiness, seizures, and other signs of brain dysfunction. The symptoms can evolve over several days, and without treatment, they progress rapidly to coma and death.
Diagnosis and Treatment
Use of a dye visible on x-rays (radiopaque dye also known as contrast) makes a subdural empyema visible on magnetic resonance imaging (MRI) or computed tomography (CT). A spinal tap is of little help and may be dangerous. In infants, a needle can sometimes be inserted directly into the empyema through a fontanelle (a soft spot between the skull bones) to drain the pus, relieve pressure, and help doctors make the diagnosis.
Subdural empyemas must be drained surgically. If the infection occurred because of an abnormality in the sinuses, the surgeon usually repairs the abnormality at the same time. Antibiotics are given intravenously.
Parasitic Infections
In some parts of the world, brain infections may be due to worms or other parasites. These infections are more common in developing countries and rural areas. They are less common in the United States.
Cysticercosis: This infection is caused by pork tapeworm larvae (see page 1223). It is the most common parasitic infection in the Western Hemisphere. After people eat food contaminated with cysticercus eggs, secretions in the stomach cause the eggs to hatch into larvae. The larvae enter the bloodstream and are distributed to all parts of the body, including the brain. The larvae form cysts that can cause headaches and seizures. The cysts degenerate and the larvae die, triggering inflammation, swelling, and symptoms such as headaches, seizures, personality changes, and mental impairment.
Sometimes the cysts block the flow of cerebrospinal fluid within the spaces of the brain (ventricles) putting pressure on the brain. This disorder is called hydrocephalus. Increased pressure can cause headaches, nausea, vomiting, and sleepiness.
Magnetic resonance imaging (MRI) or computed tomography (CT) can often show the cysts. But blood tests and a spinal tap (lumbar puncture) to obtain a sample of cerebrospinal fluid are often needed to confirm the diagnosis.
The infection is treated with albendazole or praziquantel. Corticosteroids are given to reduce the inflammation that occurs as the larvae die. Seizures are treated with anticonvulsants.
Occasionally, surgery is necessary to place a drain (shunt) to remove the excess cerebrospinal fluid and relieve the hydrocephalus. The shunt is a piece of plastic tubing placed in the spaces within the brain. The tubing is run under the skin, usually to the abdomen, where excess fluid can drain. Surgery to remove cysts from the brain may also be needed.
Other Infections: Echinococcosis (hydatid disease) and coenurosis are infections with other types of tapeworm larvae. Echinococcosis can produce large cysts in the brain. Coenurosis produces cysts, which can block the flow of fluid around the brain similar to cysticercosis.
Schistosomiasis is an infection caused by blood flukes (see page 1222).
Echinococcosis, coenurosis, and schistosomiasis can cause symptoms similar to those of cysticercosis, including seizures, headaches, personality changes, and mental impairment.
Doctors can usually diagnose these infections based on results from MRI or CT, but sometimes a spinal tap is needed. The spinal fluid may show a distinct type of inflammation with white cells called eosinophils.
These three infections are usually treated with drugs, such as albendazole, mebendazole, praziquan-tel, and pyrantel pamoate, but sometimes cysts must be removed surgically.