Definition
Encephalitis is an acute inflammatory process that affects brain tissue and is almost always accompanied by inflammation of the adjacent meninges (tissues lining the brain). There are many types of encephalitis, most of which are caused by viral infections.
Meningitis is an inflammation of the membranes (meninges) that surround the brain and spinal cord. Meningitis may be caused by many different viruses and bacteria, or by diseases that can cause inflammation of tissues of the body without infection (such as systemic lupus erythematosus). Viral meningitis is sometimes called aseptic meningitis to indicate it is not the result of a bacterial infection.
Description
Encephalitis can be divided into two forms, primary and secondary encephalitis, according to the two methods by which the viruses infect the brain. Primary encephalitis occurs when a virus directly invades the brain and spinal cord. Primary encephalitis can happen to people at any time of the year (sporadic encephalitis), or can be part of an outbreak (epidemic encephalitis). Secondary, or post-infectious encephalitis occurs when a virus first infects another organ and secondarily enters the brain.
Meningitis is an inflammation of the membranes that surround the brain and spinal cord, and may be caused by many different viruses and bacteria, or by non-infectious inflammatory diseases. Encephalitis is a distinct disease from meningitis, although, clinically, the two often share signs and symptoms of inflammation of the meninges.
Demographics
Determining the true incidence of encephalitis in the United States is difficult because reporting policies are neither standardized nor rigorously enforced. Several thousand cases of viral encephalitis are reported yearly. HSE (herpes simplex encephalitis), the most common cause of sporadic encephalitis in other western countries, is still relatively rare in the United States, with an overall incidence of two cases per one million persons per year.
Arboviruses (viruses transmitted to humans by blood-sucking insects such as mosquitoes and ticks) are the most common causes of episodic encephalitis. These statistics may be misleading because most people bitten by arbovirus-infected insects do not develop clinical disease, and only 10% of those develop overt encephalitis. Among less common causes of viral encephalitis, varicella-zoster encephalitis (a complication of the condition commonly known as shingles) has an incidence of one in 2000 infected people.
Internationally, Japanese virus encephalitis (JE), occurring principally in Japan, Southeast Asia, China, and India, is the most common viral encephalitis outside the United States.
In 1995, there were 5755 cases of bacterial meningitis reported in United States. This is a dramatic decrease from the 12,920 cases reported in 1986, probably due to the decrease in Haemophilus influenzae meningitis since the introduction of the Hib vaccine. The occurrences by infectious agents in 1995 are as follows:
- Streptococcus pneumoniae: 1.1 per 100,000 persons
- Neisseria meningitides: 0.6 per 100,000 persons
- Streptococcus: 0.3 per 100,000 persons
- Listeria monocytogenes: 0.2 per 100,000 persons
- Haemophilus influenzae: 0.2 per 100,000 persons
The incidence of meningitis in newborns has shown no significant change in the last 25 years. Viral meningitis is the most common form of aseptic meningitis and, since the introduction of the mumps vaccine, is caused by enteroviruses in up to 85% of cases. The incidence of encephalitis is more difficult to estimate because of difficulty in establishing the diagnosis. One report estimates an incidence of one in 500–1,000 infants and in the first six months of life.
Causes and symptoms
Causes
The causes of encephalitis are usually infectious, but may also be due to some noninfectious causes. Three broad categories of viruses—herpes viruses, viruses responsible for childhood infections, and arboviruses (viruses harbored by mosquitoes and ticks, and transferred through their bite)—typically trigger encephalitis.
ENCEPHALITIS AND HERPES VIRUSES Some herpes viruses that cause common infections may also cause encephalitis. These include:
- Herpes simplex virus. There are two types of herpes simplex virus (HSV) infections. HSV type 1 (HSV-1) causes cold sores or fever blisters around the mouth. HSV type 2 (HSV-2) causes genital herpes. HSV is the most common cause of sporadic encephalitis, with HSV-1 being the more common culprit. When untreated, the mortality rate from herpes simplex encephalitis is between 60–80%. That number drops to 15–20% with treatment.
- Varicella-zoster virus. This virus is responsible for chicken pox and shingles. It can cause encephalitis in adults and children, but the cases tend to be mild.
- Epstein-Barr virus. This herpes virus causes infectious mononucleosis. If encephalitis develops, it's usually mild, but more severe forms can result in death in up to 8% of cases.
ARBOVIRUSES The mosquito season varies according to geographic location. Arbovirus transmission, therefore, also varies according to season, the cycle of viral transmission, and local climatic conditions. Six encephalitis disease groups caused by arboviruses are monitored by the United States Centers for Disease Control (CDC) and include:
- St. Louis encephalitis
- West Nile encephalitis
- Powassan encephalitis
- Eastern equine encephalitis
- Western equine encephalitis
- California serogroup viral encephalitis, which includes infections with the following viruses: La Crosse, Jamestown Canyon, snowshoe hare, trivittatus, Keystone, and California encephalitis viruses.
OTHER CAUSES OF ENCEPHALITIS Bacterial pathogens (disease-causing organisms), such as rickettsial disease, mycoplasma, and cat scratch disease, are rare, but often involve inflammation of the meninges. Encephalitis can be due to parasites and fungi. Insects, such as mosquitoes in the eastern and southeastern United States can also spread encephalitis.
CAUSES OF MENINGITIS Viral meningitis is the most common infection of the Central Nervous System (CNS). It most frequently occurs in children younger than one year of age. Enteroviruses (viruses that causes infections of the gastrointestinal tract) are the most common causative agent and are a frequent cause of febrile illnesses in children. Other viral pathogens include paramyxoviruses, herpes, influenza, rubella, and adenovirus. Meningitis may occur in up to half of children younger than three months with enteroviral infections. Enteroviral infections can occur any time during the year, but are normally associated with outbreaks in the summer and fall. Viral infections cause an inflammatory response, but to a lesser degree than bacterial infections. Damage from viral meningitis may be due to an associated encephalitis and increased intracranial pressure.
Bacterial meningitis is fairly uncommon, but can be extremely serious. There are two main types of bacterial meningitis, which cause most of the reported bacterial cases: meningococcal and pneumococcal. Haempohilus influenzae type b (Hib), which was recently a major cause of bacterial meningitis, has now been almost eliminated by the vaccination of infants. The most common causative organisms in the first month of life are Escherichia coli and group B streptococci. Listeria monocytogenes infection also occurs in patients in this age range and accounts for 5–10% of cases. In people older than two months, S. pneumoniae and N. meningitides currently cause the majority of the cases of bacterial meningitis. H. influenzae may still occur, especially in children who have not received the Hib vaccine.
Symptoms
Symptoms of encephalitis include sudden fever, headache, vomiting, heightened sensitivity to light, stiff neck and back, confusion and impaired judgment, drowsiness, weak muscles, a clumsy and unsteady gait (manner of walking), bulging in the soft spots (fontanels) of the skull in infants, and irritability. More severe or late symptoms include loss of consciousness, seizures, muscle weakness, or sudden severe dementia.
Symptoms of meningitis, which may appear suddenly, often include high fever, severe and persistent headache, stiff neck, nausea, and vomiting. Changes in behavior such as confusion, sleepiness, and difficulty waking up are extremely important symptoms and may require emergency treatment.
In infants, symptoms of meningitis may include high-pitched cry, moaning cry, whimpering, dislike of being handled, fretfulness, arching of the back, neck retraction, blank, staring expression, difficulty in waking, lethargia, fever, cold hands and feet, refusing to feed or vomiting, pale, blotchy skin color. In adults, symptoms of meningitis may include vomiting, headache, drowsiness, seizures, high temperature, joint pain, stiff neck, and aversion to light.
Arboviral infections may be asymptomatic or may result in illnesses of variable severity. Arboviral meningitis is characterized by fever, headache, and stiff neck. Arboviral encephalitis is characterized by fever, headache, and altered mental status that ranges from confusion to coma. Signs of brain dysfunction such as numbness or paralysis, cranial nerve palsies, visual or hearing deficits, abnormal reflexes, and generalized seizures may also be present.
Diagnosis
Encephalitis or meningitis is suspected by a physician when the symptoms described above are present. The physician diagnoses encephalitis or meningitis after a careful examination and testing. The examination includes special maneuvers to detect signs of inflammation of the membranes that surround the brain and spinal cord (meninges). Tests that are used in the evaluation of individuals suspected of having encephalitis or meningitis include blood counts, blood cultures, coagulation studies, bacterial antigen studies of urine and serum, brain scanning, and spinal fluid analysis.
The most common method of diagnosing encephalitis and meningitis is to analyze the cerebrospinal fluid surrounding the brain and spinal cord. A needle inserted into lower spine extracts a sample of fluid for laboratory analysis, which may reveal the presence of an infection or an increased white blood cell count, a signal that the immune system is fighting an infection. The cerebrospinal fluid may also be slightly bloody if small hemorrhages have occurred. Diagnosis of herpes simplex encephalitis can be difficult, but advances using sensitive DNA methods have allowed detection of the virus in spinal fluid.
Electroencephalography (EEG) measures the waves of electrical activity produced by the brain. It is often used to diagnose and manage seizure disorders. A number of small electrodes are attached to the scalp. The patient remains still during the test and at times may be asked to breathe deeply and steadily for several minutes or to stare at a patterned board. At times, a light may be flashed into eyes. These actions are meant to stimulate the brain. The electrodes pick up the electrical impulses from brain and send them to the EEG machine, which records the brain waves on a moving sheet of paper. An abnormal EEG result may suggest some of diseases, but a normal result does not rule them out.
Brain imaging, using computed tomography (CT) or magnetic resonance imaging (MRI) may reveal swelling of brain. These techniques may reveal another condition with signs and symptoms that are similar to encephalitis, such as a concussion.
Rarely, if diagnosis of herpes simplex encephalitis isn't possible using DNA methods or by CT or MRI scans, a physician may take a small sample of the brain tissue, or biopsy, for analysis to determine if the virus is present. Physicians usually attempt treatment with antiviral medications before suggesting brain biopsy.
Blood testing can confirm the presence of West Nile virus in the body by drawing a sample of blood for laboratory analysis. When infected with West Nile virus, an analysis of blood sample may show a rising level of an antibody against the virus, a positive DNA test for the virus or a positive virus culture.
Treatment team
The treatment team may include a pediatrician or a general practitioner, an infectious disease specialist and/or a critical care specialist, a neurosurgeon, a neurologist or a neonatologist. Others professionals may give support during hospitalization for intravenous antibiotics or other specific procedures.
Treatment
Treatment for meningitis depends on the cause and on the symptoms. Antiviral medications may be used if a virus is involved. Antibiotics are prescribed for bacterial infections. If the causative organism is unknown, antibiotic regimes can be based on the child's age. In infants aged 30 days or younger, ampicillin is usually prescribed along with an aminoglycoside or a cephalosporin (cefotaxime) medication. In children aged 30–60 days, ampicillin and a cephalosporin (ceftriaxone or cefotaxime) can also be used. However, since S. pneumoniae occasionally occurs in this age range, vancomycin should be part of treatment instead of ampicillin. In older children, cephalosporin or ampicillin plus chloramphenicol can be used. Often, rifampicin is given (in meningococcal bacterial meningitis cases) as a preventative measure to roommates, close family members, or others who may have come in contact with an infected person.
In addition, anticonvulsant medications may be used if there are seizures. Corticosteroids may be needed to reduce brain swelling and inflammation. Dexamethasone is usually indicated for children with suspected meningitis who are older than six weeks and is recommended for treatment of infants and children with H. influenzae meningitis. Sedatives may be needed for irritability or restlessness and over-the-counter medications may be used for fever and headache.
Until a bacterial cause of CNS inflammation is excluded, the treatment should include parenteral (given by injection) antibiotics. Treatment with a third-generation cephalosporin antibiotic, such as cefotaxime sodium (Claforan) or ceftriaxone sodium (Rocephin), is usually recommended. Vancomycin (Lyphocin, Vancocin, Vancoled) should be added in geographic areas where strains of S. pneumoniae resistant to penicillin and cephalosporins have been reported.
Encephalitis can be difficult to treat because the viruses that cause the disease generally don't respond to many medications. The exceptions are herpes simplex virus and varicella-zoster virus, which respond to the antiviral drug acyclovir, and is usually administered intravenously in the hospital for at least ten days.
Treatment is available for many symptoms of encephalitis. Patients with headache should rest in a quiet, dark environment and take analgesics. Narcotic therapy may be needed for pain relief; however, medication induced changes in level of consciousness should be avoided. Anticonvulsant medication and anti-inflammatory drugs to reduce swelling and pressure within the skull are usually prescribed. Otherwise, treatment mainly consists of rest and a healthy diet including plenty of liquids.
Recovery and rehabilitation
As opposed to many untreatable neurological conditions, encephalitis and meningitis are diseases that, given the adequate treatment described above, often resolve with complete recovery. It is very important that the disease's cause is promptly identified and treated before any complication is irreversibly established. Physical and speech therapy are often helpful when neurological deficits remain, as are occupational therapists and audiologists.
Clinical trials
The National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Neurological Disorders and Stroke (NINDS) support and conduct research on encephalitis and meningitis. Much of this research is aimed at learning more about the cause(s), prevention, and treatment of these disorders. Ongoing clinical trials as of early 2004 include:
- Valacyclovir for long-term therapy of Herpes simplex encephalitis; IVIG—West Nile encephalitis: Safety and Efficacy; Structure of the Herpes Simplex Virus Receptor; sponsored by National Institute of Allergy and Infectious Diseases
- Natural History of West Nile Virus Infection; Omr-IgG-am™ for Treating Patients with or at High Risk for West Nile Virus Disease; sponsored by Warren G. Magnuson Clinical Center
- Intrathecal Gemcitibine to Treat Neoplastic Meningitis; Intrathecal Gemcitabine in Treating Patients with Cancer and Neoplastic Meningitis; sponsored by Baylor College of Medicine
Updated information on clinical trials can be found at the National Institutes of Health clinical trials website at www.clinicaltrials.org.
Prognosis
The prognosis for encephalitis varies. Some cases are mild, short and relatively benign and patients have full recovery. Other cases are severe, and permanent impairment or death is possible. The acute phase of encephalitis may last for one to two weeks, with gradual or sudden resolution of fever and neurological symptoms. Neurological symptoms may require many months before full recovery. Prognosis for people with viral meningitis is usually good.
With early diagnosis and prompt treatment, most patients recover from meningitis. However, in some cases, the disease progresses so rapidly that death occurs during the first 48 hours, despite early treatment. Permanent neurological impairments including memory, speech, vision, hearing, muscle control, and sensation difficulties can occur in people who survive severe cases of meningitis and encephalitis.
The prognosis for appropriately treated meningitis has improved, but there is still a 5% mortality rate and significant morbidity (lasting impairment). The prognosis varies with the age of the person, clinical condition, and infecting organism.
Special concerns
A person's exposure to mosquitoes and other insects that harbor arboviruses can be reduced by taking precautions when in a mosquito-prone area. Insect repellents containing DEET provide effective temporary protection form mosquito bites. Long sleeves and pants should be worn when outside during the evening hours of peak mosquito activity. When camping outside, intact mosquito netting over sleeping areas reduces the risk of mosquito bites. Communities also employ large-scale spraying of pesticides to reduce the population of mosquitoes, and encourage citizens to eliminate all standing water sources, such as in bird baths, flower pots, and tires stored outside to eliminate possible breeding grounds for mosquitoes.
Although large epidemics of meningococcal meningitis do not occur in the United States, some countries experience large, periodic outbreaks. Overseas travelers should check to see if meningococcal vaccine is recommended for their destination. Travelers should receive the vaccine at least one week before departure, if possible. A vaccine to prevent meningitis due to S. pneumoniae (also called pneumococcal meningitis) can also prevent other forms of infection due to S. pneumoniae. The pneumococcal vaccine is not effective in children under two years of age, but it is recommended for all individuals over 65 years of age and younger people with certain chronic medical conditions.
Resources
BOOKS
Kandel, Eric R. Principles of Neural Science. New York: McGraw-Hill/Appleton & Lange, 2000.
Kolb, Bryan, and Ian Q. Whishaw. Introduction to Brain and Behavior. New York: W. H. Freeman & Co, 2001.
Roos, Karen L. Meningitis: 100 Maxims. London: Edward Arnold, 1996.
PERIODICALS
Chandesris, M. O., et al. "A case of Influenza virus encephalitis in south of France." Rev Med Interne 25 (2004): 78–82.
Kurt-Jones, E. A., et al. "Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis." Proc Natl Acad Sci USA (2004): 1315–1320.
OTHER
Information on Arboviral Encephalitides. Centers for Disease Control and Prevention. (April 10, 2004). http://www.cdc.gov/ncidod/dvbid/arbor/arbdet.htm
NINDS Encephalitis and Meningitis Information Page. National Institutes of Neurological Disorders and Stroke. (April 10, 2004). http://www.ninds.nih.gov/health_and_medical/disorders/encmenin_doc.htm
Top 20 Meningitis FAQs. Meningitis Foundation of America. (April 10, 2004). http://www.musa.org/faqs.htm
ORGANIZATIONS
Meningitis Foundation of America, Inc. 7155 Shadeland Station Suite 190, Indianapolis, Indiana 46256-3922. (317) 595-6383 or (800) 668-1129; Fax: (317) 595-6370. support@musa.org. http://www.musa.org/.
National Institute of Allergy and Infectious Diseases (NIAID). 31 Center Drive, Rm. 7A50 MSC 2520, Bethesda, Maryland 20892-2520. (301) 496-5717. http://www.niaid.nih.gov/.
Centers for Disease Control and Prevention (CDC), Division of Vector-Borne Infectious Diseases. P.O. Box 2087, Fort Collins, Colorado 80522. (800) 311-3435. dvbid@ cdc.gov. http://www.cdc.gov/ncidod/dvbid/index.htm.
Bruno Marcos Verbeno
Iuri Drumond Louro, M.D., Ph.D.
