Aseptic Meningitis Last Updated: March 14, 2005 Rate this Article Definition Aseptic meningitis is an illness characterized

by serous inflammation of the linings of the brain (ie, meninges), usually with an accompanying mononuclear pleocytosis. Clinical symptomatology is varied and includes predominantly headache and fever. The illness is usually mild and runs its course without treatment; however, some cases can be severe and life threatening. Aseptic meningitis syndrome is not caused by pyogenic bacteria, but can be caused by multiple conditions including infectious viral and nonviral causes and many noninfectious etiologies. Hence, this term is no longer synonymous with viral meningitis, although the two often are used interchangeably. Background Aseptic meningitis is a common, rarely fatal condition usually caused by certain viruses. Fortunately, most people exposed to these viruses experience no symptoms or only mild symptoms without meningitis. Meningitis means inflammation of the membranes covering the brain and spinal cord. OVERVIEW AND GENERAL INFORMATION Section 3 of 9 Author Information Introduction Overview And General Information Specific Causes Evaluation And Diagnosis Treatment Differential Diagnosis, Complications, Prognosis, And Prevention Related Conditions Bibliography Frequency Aseptic meningitis is one of the most common infections of the meninges. It occurs in individuals of all ages, although it is more common in children, especially during summer. No racial differences are reported. Aseptic meningitis tends to occur 3 times more frequently in males than in females. In meningitis caused by the mumps virus, both sexes are affected equally. Causes, incidence, and risk factors The most common causes of viral meningitis are the enteroviruses, herpesviruses, and HIV. HIV may cause aseptic meningitis, mostly at the time of seroconversion. While HIV spreads via the hematogenous route, rabies, polio, and herpesviruses are neurotrophic (ie, spread through neurons). Coxsackieviruses and echoviruses, which are types of enteroviruses, account for approximately half of cases of aseptic meningitis. Other enteroviruses and mumps are additional causes. The incidence of these infections increases in the summer and early fall. Enteroviruses are spread by hand-to-mouth contact and to a

lesser extent by respiratory and fecal routes. Among viruses, enteroviruses are the most common cause of aseptic meningitis. These are small, nonenveloped RNA viruses of the picornavirus family with various serotypes. More than 50 subtypes have been linked with meningitis. Adenoviruses are respiratory viruses that rarely cause meningitis. Mumps was a common cause of aseptic meningitis in the United States until the mumps vaccination came into use. In several countries, mumps virus remains a common pathogen in aseptic meningitis. It is spread by respiratory secretions, with increased incidence in the spring. Herpesvirus, both type 1 (herpes simplex [HSV] or herpes labialis) and type 2 (genital herpes), can cause meningitis in children and especially infants. Varicella-zoster virus, another herpesvirus, causes encephalitis but only in those who are immunocompromised. Geographic and seasonal patterns of arbovirus infection depend on the life cycle of arthropod vectors, animal reservoirs, and their contact with human subjects. Eastern equine encephalitis virus (EEEV) usually is observed in Atlantic and Gulf regions, whereas western equine encephalitis virus (WEEV) is prevalent in the western part of the United States. WEEV is responsible for more aseptic meningitis cases than EEEV. Approximately 15% of St Louis encephalitis virus (SLEV) infections result in meningitis. In children, this incidence is as high as 60%. SLEV infection can occur in both rural and urban areas. In the rural setting, the virus tends to follow the same pattern as WEEV. Conversely, in urban settings, outbreaks tend to be more explosive. Approximately 18% of people infected with Colorado tick fever develop meningitis. This infection primarily occurs in the Rocky Mountain area, because Dermacentor andersoni ticks that are infected by the virus are limited to the western mountainous areas. Only 3% of patients with Venezuelan encephalitis are known to develop acute meningitis. This virus has spread into Florida and some southwestern states. Initially, it leads to influenzalike illness in most people. Lymphocytic choriomeningitis virus (LCMV), an arenavirus, is an extremely rare cause of meningitis. LCMV infection occurs by contact with dust or food contaminated by excreta of rodents. These cases tend to be more common in the winter. Human infections tend to occur in both laboratory and home settings. Viral meningitis is a relatively common disorder. In one county in Minnesota, the incidence of viral meningitis was 10.9 per 100,000 person-years from 1950 to 1981, with most cases occurring in the summer months. Incidence of aseptic meningitis has been reported as 11 per 100,000 person-years, compared to a rate of 8.6 per 100,000 for bacterial meningitis. In the United States, a specific cause is usually identifiable in 10-15% of cases of meningitis. Pathophysiology

When the protecting barriers of the brain, including the skull, meninges, and blood-brain barrier, are broached by a pathogen, meningitis can result. Predisposing factors include preexisting diabetes mellitus, immunosuppression, otitis media, pneumonia, sinusitis, and alcohol abuse. Meningeal inflammation and irritation elicit a protective reflex to prevent stretching of the inflamed and hypersensitive nerve roots, which is detectable clinically as neck stiffness or meningeal signs. Meningeal irritation due to inflammation also may cause headache and cranial nerve palsies. When cerebral edema and elevated intracranial pressure occur, alterations in mental status, headache, vomiting, seizures, and cranial nerve palsies may ensue. Clinical features Most acute viral meningitides produce symptoms with variations depending on the particular virus. Some individuals may experience a biphasic type of illness with nonspecific constitutional symptoms followed by meningitis. The viruses that commonly cause aseptic meningitis may be spread for weeks after infection. The time course of acute viral meningitis varies. The onset may occur within a matter of hours or evolve more slowly over a few days. Usually, maximum deficit appears within 3-6 days after exposure. Headache, fever, stiff neck, photophobia, drowsiness, myalgias, malaise, chills, sore throat, abdominal pain, nausea, and vomiting usually characterize acute viral meningitis. Focal signs, seizures, and profound lethargy are rarely a part of this syndrome. The diagnosis may be suggested by associated skin manifestations such as the rash of varicella zoster, genital lesions for HSV-2, or a mild maculopapular rash occurring in the summer and fall months with enteroviruses. Occasionally, patients may exhibit altered levels of consciousness including confusion and visual hallucinations. Meningeal signs Neck stiffness in meningitis is tested by gentle forward flexion of the neck with the patient lying in the supine position. Meningeal irritation also can be tested by the jolt accentuation of headache. This is tested by asking the patient to turn his or her head horizontally at a frequency of 2-3 rotations per second. Worsening of a baseline headache represents a positive sign. Severe meningeal irritation may result in the patient assuming the tripod position (termed Amoss sign or Hoyne sign) with the knees and hips flexed, the back arched lordotically, the neck extended, and the arms brought back to support the thorax.

When passive neck flexion in a supine patient results in flexion of the knees and hips, a positive Brudzinski sign is entertained. Yet another sign, the contralateral reflex, is present if passive flexion of one hip and knee causes flexion of the contralateral leg. Kernig sign is elicited with the patient lying supine and the hip flexed at 90. A positive sign is present when extension of the knee from this position elicits resistance or pain in the lower back or posterior thigh. Papilledema or absence of venous pulsations upon funduscopic examination indicates increased intracranial pressure. Rash Some enteroviral infections produce a rash that usually accompanies the onset of fever and persists for 4-10 days. In infections due to coxsackieviruses A5, 9, or 16 or echoviruses 4, 6, 9, 16, or 30, the rash is typically maculopapular and nonpruritic, may be confined to the face and trunk, or may involve extremities, including the palms and soles. In coxsackievirus A16 and, rarely, in other group A serotype infections, a vesicular rash may involve the hands, feet, and oropharynx. Herpangina, characterized by gray vesicular lesions on the tonsillar fossae, soft palate, and uvula, can accompany infection caused by group A coxsackievirus. With echovirus 9 infections, a petechial rash resembling meningococcemia typically is observed. The epidemiologic setting (eg, time of year, exposure to insects, local community) and accompanying systemic manifestations may be helpful in making a presumptive diagnosis. Most importantly, remember that with a few exceptions, the clinical and laboratory findings accompanying acute viral meningitis are insufficiently distinct to allow an etiologic diagnosis, and distinguishing these disorders from a number of nonviral diseases may be difficult. SPECIFIC CAUSES Section 4 of 9 Author Information Introduction Overview And General Information Specific Causes Evaluation And Diagnosis Treatment Differential Diagnosis, Complications, Prognosis, And Prevention Related Conditions Bibliography

Human immunodeficiency virus infections HIV infects and selectively destroys T4 lymphocytes, causing immunodeficiency. As a result of this acquired immunodeficiency, patients are prone to opportunistic infections. In particular, patients are susceptible to toxoplasmosis, cryptococcosis, other fungal infections, cytomegalovirus, and papovavirus infections. They also develop cerebral or other extranodal B-cell lymphomas. This is due to loss of the surveillance function of T

cells. HIV also infects the CNS directly, causing aseptic meningitis, encephalitis, leukoencephalopathy, and myelopathy. HIV encephalitis is characterized by progressive intellectual impairment, behavior disturbances, and sensorimotor deficits. DNA analysis helps to detect HIV in the brains of these patients, and HIV-specific immunoglobulin is produced intrathecally. Congenital HIV encephalitis is more severe than the adult forms and may result in microcephaly and basal ganglia calcification. Nonviral infectious etiologies In contrast to the viral causes of aseptic meningitis, nonviral causes of meningitis usually have a more complicated course and always must be considered because they can be managed with specific treatments. Consider partially treated bacterial meningitis, especially in the presence of a history of previous oral antimicrobial therapy and when cerebrospinal fluid (CSF) exhibits persistently low glucose or polymorphonuclear pleocytosis. Latex agglutination tests may be useful in these patients. Tuberculous meningitis In a healthy host, CNS tuberculosis usually takes the form of a meningitis that causes an acute-to-subacute illness characterized by fever, headache, drowsiness, meningism, and confusion over a period of approximately 2-3 weeks. Less frequent presentations include atypical febrile seizures in children, isolated cranial nerve palsies, bilateral papilledema, and acute confusional states. Tuberculous meningitis (TBM) is difficult to diagnose, and a high index of suspicion is needed for making an early diagnosis. Elucidate the patient's recent contact with tuberculosis. The prodrome is usually nonspecific, including headache, vomiting, photophobia, and fever. In one study, only 2% of subjects reported meningitic symptoms. The duration of presenting symptoms may vary from 1 day to 9 months, although 55% of individuals presented with symptoms of fewer than 2 weeks' duration. In 1948, British Medical Research Council developed a method for staging the severity of the disease. Stage I describes the early nonspecific symptoms and signs including apathy, irritability, headache, malaise, fever, anorexia, nausea, and vomiting, without any alteration in the level of consciousness. Stage II describes altered consciousness without coma or delirium but with minor focal neurological signs. Symptoms and signs of meningism and meningitis are present, in addition to focal neurological deficits, isolated cranial nerve palsies, and abnormal involuntary movements. Stage III describes an advanced state with stupor or coma, dense neurological deficits, seizures, posturing, and/or abnormal movements. The prognosis is related directly to the clinical stage of diagnosis. The occurrence of the syndrome of inappropriate antidiuretic hormone secretion is common and also is linked to a poor prognosis.

Apart from papilledema, fundus examination occasionally may reveal the presence of a retinal tuberculoid, a small grayish white choroidal nodule, highly suggestive of tuberculosis. These lesions are said to be more common in miliary disease than in other forms. Tremor is the most common movement disorder observed in the course of TBM. Chorea more frequently is found in young children. Deep vascular lesions are more common among patients with movement disorders. Tuberculous radiculomyelitis (TBRM) is a complication of TBM that rarely has been reported in the modern medical literature. TBRM develops at various periods after TBM, even in patients who are treated adequately after sterilization of the CSF. The most common symptoms are subacute paraparesis, radicular pain, bladder disturbance, and subsequent paralysis. CSF evaluation usually demonstrates an active inflammatory response with a very high protein level. MRI and CT scans are critical in making the diagnosis, revealing loculation and obliteration of the subarachnoid space along with linear intradural enhancement. As in other forms of paradoxical reactions to antituberculous treatment, evidence exists that steroid treatment may have a beneficial effect. In addition, 2 rare forms of TBM include tuberculous serous meningitis, characterized by signs and symptoms of a mild meningitis with spontaneous recovery, and tuberculous encephalopathy, which usually occurs in a young child with progressive primary TB: the presentation of a reduced level of consciousness with few focal signs and meningismus is typical. Diffuse edema and white matter pallor with demyelination are found pathologically. The pathogenesis is uncertain but is presumed to be immune mediated. Diagnosis is important, because anecdotal reports suggest a good response to corticosteroids. TBM may have an acute presentation. Sometimes it may present with cranial nerve deficits, or it may have a more indolent course involving headache, meningismus, and altered mental status. CSF findings include elevated opening pressure, protein levels of 100-500 mg/dL, WBC count of 10-500/mm3, and hypoglycorrhachia. Since bacterial cultures require several weeks, the polymerase chain reaction (PCR) technique for Mycobacterium tuberculosis may be very useful. Brucellosis Brucellosis is an infection with a bacterium of one of the Brucella species, usually Brucella abortus (cattle), Brucella melitensis, Brucella ovis (sheep, goats), Brucella suis (pigs), or rarely Brucella canis (dogs). Its distribution is worldwide, but it is most common in the Mediterranean regions, Africa, the Middle East, India, Central Asia, Mexico, and Central and South America. Persons at highest risk of brucellosis are those who work with animals that are infected, such as veterinarians and ranchers, and persons who consume raw milk or cheeses made with raw milk. Brucellosis also may be transmitted to humans if they are exposed inadvertently to live brucellosis vaccine by a needlestick or other accident.

The incidence in the United States is fewer than 0.5 cases per 100,000 population. Clinical symptoms are extremely variable. The most common presentation is of symptoms appearing 1-2 months after exposure. In the acute form, brucellosis takes the form of a flulike illness, with fever, sweats, malaise, anorexia, headache, myalgia, and back pain. In the undulant form (<1 year from onset of illness), symptoms include undulant fevers, arthritis, and orchiepididymitis in males. Neurological sequelae occur in as many as 5% of patients. In the chronic form (>1 year from onset), a chronic fatigue syndrome-like picture with depression and arthritis is typical. Other complications of brucellosis include granulomatous hepatitis, spondylitis, anemia, leukopenia, thrombocytopenia, uveitis, optic neuritis, papilledema, and endocarditis. Diagnosis is confirmed by the isolation of bacteria from the Brucellaceae family from a bacterial culture or an increase over time in antibodies in the blood that are specific for Brucella species. Other etiologies Lyme meningitis manifests several weeks after the skin lesions have appeared but may occur while erythema migrans lesions are still present. Hypoglycorrhachia is not a prominent finding in the CSF. Facial nerve palsy, sometimes bilaterally, may be observed. Acute monocytic ehrlichiosis is another tick-borne infection that may present similarly to aseptic meningitis. Laboratory tests may reveal pancytopenia and elevated hepatic transaminases, BUN, and creatinine. Syphilitic meningitis is becoming more common in the AIDS era. It may coexist with the primary infection or follow it by as many as 2 years. Because of the lack of a typical clinical presentation, CSF Venereal Disease Research Laboratory test (VDRL) always must be included in the workup of aseptic meningitis. Fungal meningitis occurs primarily in patients with AIDS and after organ transplantation, immunosuppressive chemotherapy, or long-term corticosteroid therapy. Nonetheless, the most common fungal meningitis pathogen, Cryptococcus neoformans, can occur in immunocompetent patients. Cryptococcal antigen assay on CSF can be helpful in these situations. Summary - Differential diagnosis of aseptic meningitis syndrome Infectious etiologies Viruses Enteroviruses - Polio, coxsackievirus, echovirus HSV types 1 and 2 Varicella-zoster virus Adenovirus Epstein-Barr virus LCMV

HIV Influenza virus types A and B Bacteria Partially treated meningitis Parameningeal infection Endocarditis Mycoplasma pneumoniae M tuberculosis Ehrlichiosis - Monocytic, granulocytic Borrelia burgdorferi Treponema pallidum Brucella species Fungi C neoformans Histoplasma capsulatum Coccidioides immitis Blastomyces dermatitides Parasites Toxoplasma gondii Taenia solium (cysticercosis) Noninfectious causes Drugs Nonsteroidal anti-inflammatory drugs (NSAIDs)

Trimethoprim-sulfamethoxazole, amoxicillin OKT3 Azathioprine Intravenous immunoglobulin Isoniazid Intrathecal methotrexate Intrathecal cystine arabinoside Vaccination Allopurinol Systemic diseases Sarcoidosis Leptomeningeal cancer Posttransplantation lymphoproliferative disorder Systemic lupus erythematosus Wegener granulomatosis CNS vasculitis Behet disease Vogt-Koyanagi-Harada syndrome Miscellaneous Arachnoiditis Migraine Postinfectious syndromes Quick Find Author Information

Introduction Overview And General Information Specific Causes Evaluation And Diagnosis Treatment Differential Diagnosis, Complications, Prognosis, And Prevention Related Conditions Bibliography Click for related images. Continuing Education CME available for this topic. Click here to take this CME. Patient Education Click here for patient education.

EVALUATION AND DIAGNOSIS Section 5 of 9 Author Information Introduction Overview And General Information Specific Causes Evaluation And Diagnosis Treatment Differential Diagnosis, Complications, Prognosis, And Prevention Related Conditions Bibliography

Suspicion of viral meningitis is based on the clinical presentation and presence of certain CSF findings. Presence of less than 500 mononuclear cells/mm3 of CSF (pleocytosis) is characteristic. Occasionally, early examination may reveal acellular fluid or predominance of polymorphonuclear leukocytes, but the typical mononuclear pleocytosis develops in 8-48 hours. CSF pressure may be elevated, whereas the glucose level is characteristically normal or only modestly decreased. CSF protein level usually is elevated (50-100 mg/dL). Other test results include negative bacterial antigen tests and low levels of tumor necrosis factor (TNF) and lactate.

If performed, immunoglobulin concentration and oligoclonal bands may be noted. Increased protein content and pleocytosis may persist for months after convalescence; oligoclonal bands may remain detectable even longer. PCR screening of CSF has become an important diagnostic tool and can help in the isolation of several viruses. Sometimes, the organism may be detected directly in the CSF, blood, or stool, but usually the diagnosis is based on serologic tests. Choice of tests and their interpretation depend on the particular organism involved. Culture is the criterion standard for diagnosis, but it may not be positive in all patients. Direct viral isolation is of limited value in making the diagnosis, since it takes several days. Arboviruses and enteroviruses can be isolated from the blood but seldom are recoverable at the time of clinically evident meningitis. Coxsackievirus and echovirus can be isolated from stool or CSF and sometimes from throat swabs. Mumps virus can be isolated from saliva, throat swabs, or CSF. HSV-2 can be cultured from CSF or swabs taken from genital lesions. LCMV can be isolated from CSF or blood. Seroconversion, demonstrated by a 4-fold or higher increase in antibody titer between acute and convalescent sera, can be helpful in making a diagnosis. However, virus-specific immunoglobulin M (IgM) antibodies provide a quick and more accurate early diagnosis. Serum laboratory findings can be highly variable and depend on the causative agent. The WBC count usually is not elevated, but an increase or decrease can occur, usually with a lymphocytic predominance. A high serum amylase level is observed in patients with mumps because of involvement of the salivary glands or pancreas. CT scan and MRI are not helpful in making the diagnosis of aseptic meningitis. They are performed for excluding alternative diagnoses in certain situations. Chest x-ray may be indicated when tuberculosis is suspected as an underlying cause. Tuberculin skin test also may be indicated when tuberculosis is suspected as an underlying cause of aseptic meningitis. Summary of appropriate diagnostic investigations Lab tests

CBC, differential, platelet count Sedimentation rate, antinuclear antibody, rheumatoid factor Sjgren syndrome antigens A and B Serum protein electrophoresis Lyme titer (enzyme-linked immunosorbent assay [ELISA]) VDRL, fluorescent treponemal antibody absorption test (FTA-ABS) Acute and convalescent sera for virus-specific IgG or IgM to enteroviruses, arboviruses, adenoviruses, LCMV, Epstein-Barr virus, and HSV-2 Imaging studies Chest x-ray, posteroanterior and lateral MRI of brain/spine Other - Intradermal tuberculin test (purified protein derivative [PPD]) CSF studies Gram stain, bacterial culture and sensitivity Acid-fast bacillus, India ink Cryptococcal antigen Cell count Protein, glucose, and gamma globulin Latex agglutination test for Haemophilus influenzae type b VDRL, FTA-ABS PCR for HSV (varicella-zoster virus also in immunocompromised patients), M tuberculosis Virus-specific IgM antibodies to B burgdorferi and Brucella, Histoplasma, and Coccidioides species Angiotensin-converting enzyme (ACE) level

Tuberculostearic acid Cytology Clinical diagnosis The diagnosis of viral meningitis is based on the clinical presentation and CSF findings that include lymphocyte-predominant pleocytosis of fewer than 500 cells per mm3, normal glucose concentration, normal or slightly elevated protein, and negative bacterial antigen tests. Other findings, including low concentrations of TNF and lactic acid, add further validity. As a potent mediator of inflammation, the cytopathic cytokine TNF has been considered to be a strong candidate in the pathogenesis of CNS diseases such as meningitis as well as demyelinating disease (and its animal model, experimental autoimmune encephalomyelitis). In patients with multiple sclerosis, production of TNF alpha is significantly higher before exacerbation than in stable disease. TNF alpha has been demonstrated to have potential as a predictor of clinical outcome in children with acute bacterial meningitis. TNF alpha was markedly higher in children with acute bacterial meningitis than in controls. All patients with TNF alpha levels greater than 1500 pg/mL died. TREATMENT Section 6 of 9 Author Information Introduction Overview And General Information Specific Causes Evaluation And Diagnosis Treatment Differential Diagnosis, Complications, Prognosis, And Prevention Related Conditions Bibliography

Empiric antibiotic coverage Given the potential for serious neurological morbidity and the persistently high mortality rates of bacterial meningitis, rapid institution of antibiotic coverage is essential when the diagnosis of bacterial meningitis is suspected. Most studies suggest that rapid sterilization of CSF reduces mortality and long-term sequelae rates. Generally, if imaging studies are indicated before lumbar puncture, blood cultures and empiric antibiotic therapy should be instituted before the imaging studies; these are unlikely to decrease diagnostic sensitivity if CSF is tested for bacterial antigens. No specific treatment exists for most of the viruses; therefore, treatment, for the most part, is supportive and includes analgesics, antinausea medications, intravenous fluids, and prevention and treatment of complications.

Headache and fever usually can be treated with judicious doses of acetaminophen. Severe hyperthermia (>40C) may require vigorous therapy, but mild temperature elevation may serve as a natural defense mechanism, and some people believe it should be left untreated. Strict isolation is not necessary. When enteroviral infection is suspected, take precautions in handling stools and wash hands carefully. Persons with measles, chickenpox, rubella, or mumps virus infections also should observe the usual precaution of isolation from susceptible individuals. Antiviral therapy Effective antiviral therapy is available against HSV-1, varicella, and cytomegalovirus. In immunosuppressed patients, long-term therapy may be necessary. Acyclovir antiviral therapy is recommended for immunocompetent hosts with HSV-2 meningitis and a primary genital herpes infection. Valacyclovir has become available for recurrent genital herpes but provides no advantage over acyclovir. The general trend is to avoid corticosteroids because of their inhibitory effects on host immune responses. Nucleoside analogs, such as acyclovir, initially are phosphorylated by viral thymidine kinase to eventually form a nucleoside triphosphate. These molecules inhibit HSV polymerase with 30-50 times the potency of human alpha-DNA polymerase. For meningitis caused by HSV-2, acyclovir is the drug of choice. Valacyclovir and foscarnet are alternative antiviral agents. Triple drug therapy, using isoniazid, rifampin, and pyrazinamide, is the most appropriate choice for tuberculosis. For unusual bacteria, broad-spectrum antibiotics are excellent. Penicillin and ceftriaxone are used for meningitis caused by actinomycetes and spirochetes. Doxycycline or rifampin is an excellent choice for Brucella infection. Gentamicin can be used for infections caused by Pasteurella tularensis. Antifungal agents of choice include amphotericin B, fluconazole, and flucytosine. Occasionally, glucocorticoids, such as dexamethasone, are useful when meningitis is associated with signs of increased intracranial pressure. Remarkable recovery may be achieved in some patients who become comatose. Vigorous support and avoidance of complications are very important in these patients.

For severe cases, meticulous care in an intensive care setting with respiratory and nutritional support is warranted. Many patients who have aseptic meningitis can be cared for on an outpatient basis, but those who have profound headache, nausea, vomiting, or CSF pleocytosis with a polymorphonuclear leukocyte predominance should be admitted for observation with antibiotic coverage for bacterial meningitis at the discretion of the managing clinician. Specific diagnosis is useful for prognosis of an individual patient and for epidemiologic aspects of the population that is at risk. Patients with measles, chickenpox, rubella, or mumps virus infections must be isolated from susceptible individuals. Effective vaccines are available for polio, measles, mumps, and rubella. Illnesses related to these viruses have declined dramatically in countries with effective vaccination strategies. Vaccination against Japanese encephalitis has been effective in controlling the infection in Asia. A vaccine against varicella recently has been introduced. Rabies is the only infection in which the vaccine is given after exposure to the virus. DIFFERENTIAL DIAGNOSIS, COMPLICATIONS, PROGNOSIS, AND PREVENTION Section 7 of 9 Author Information Introduction Overview And General Information Specific Causes Evaluation And Diagnosis Treatment Differential Diagnosis, Complications, Prognosis, And Prevention Related Conditions Bibliography

Differential diagnosis Since no specific treatment is available for acute viral meningitis in immunocompetent individuals (except meningitis due to herpes) and since the presentation is often nonspecific, exclusion of other conditions becomes highly important. Until CSF findings become available, the differential diagnosis of aseptic meningitis is very broad, encompassing many toxic and vascular diseases including those listed in Specific Causes. Complications Seizures sometimes can complicate meningitis; however, prophylactic anticonvulsants are not recommended routinely. If seizures develop, they can be controlled with phenytoin and phenobarbital. If status epilepticus develops, appropriate therapy should be provided to prevent secondary brain injury.

Encephalitis may develop in some patients. The most common sequela following mumps meningoencephalitis is sensorineural deafness. Hydrocephalus from aqueductal stenosis has been reported as a late sequela of mumps meningitis and encephalitis in children. If persistent cognitive problems occur after recovery from acute meningitis, especially in terms of residual suboptimal functioning in the workplace or in school, referral for formal neuropsychological testing clarifies the nature of the complaint both to the physician and to the patient and helps separate psychological adjustment factors from organic dysfunction. Full recovery from viral meningitis usually occurs within 1-2 weeks of onset, though fatigue, lightheadedness, and asthenia may persist for months in some patients. Aseptic meningitis has low rates of morbidity and mortality, except when it occurs in the perinatal period. Advise individuals to call their health care provider if symptoms of aseptic meningitis develop. Prognosis Aseptic meningitis is usually a benign disease; most people exposed to these viruses experience either no symptoms or mild symptoms, and they usually experience full recovery in 5-14 days after onset of symptoms. However, fatigue and lightheadedness may persist longer in some people. Prevention Hand washing, immunization (eg, against mumps), and other general good health measures may reduce the risk of developing an infection that can progress to meningitis. Many of the causes of meningitis are communicable and, if one case of meningitis is diagnosed within a community, appropriate steps may need to be taken immediately to prevent the further spread of the disease. Since viruses that are passed in the stool cause most cases, people diagnosed with aseptic meningitis should be sure to wash their hands thoroughly after using the toilet. Always wash hands after changing diapers. RELATED CONDITIONS Section 8 of 9 Author Information Introduction Overview And General Information Specific Causes Evaluation And Diagnosis Treatment Differential Diagnosis, Complications, Prognosis, And Prevention Related Conditions Bibliography

Drug-induced aseptic meningitis

The incidence of drug-induced meningitis (DIAM) is unknown. Many antimicrobials, such as trimethoprim-sulfamethoxazole, ciprofloxacin, cephalexin, metronidazole, amoxicillin, penicillin, and isoniazid, are causes of aseptic meningitis. In addition, the xanthine oxidase inhibitor allopurinol has been implicated in causing aseptic meningitis. DIAM is a complication in which numerous other drugs, namely nonsteroidal anti-inflammatory drugs (NSAIDs), ranitidine, carbamazepine, vaccines against hepatitis B and mumps, immunoglobulins, OKT3 monoclonal antibodies (ie, directed against the T3 receptor and, therefore, pan T-cell antibodies), co-trimoxazole, radiographic agents, and muromonabCD3, also have been associated. A high index of suspicion is needed to make an accurate diagnosis of DIAM. Diagnostic accuracy in clinical care depends on a complete history and physical examination. The clinical presentation does not help in differentiating DIAM from infectious meningitis. The CSF profile (ie, neutrophilic pleocytosis) does not allow DIAM to be distinguished from infectious meningitis. Systemic lupus erythematosus is the single most frequent underlying condition associated with DIAM. Recurrent DIAM is well known; females usually predominate, and the frequency varies with the different underlying conditions. Pathophysiology The pathogenic mechanisms of DIAM are diverse and presumably differ from drug to drug. A hypersensitivity mechanism (especially types 1 and 3) is considered for cases related to NSAIDs, intravenous immunoglobulin, and antibiotics. OKT3 cases are believed to be mediated, at least in part, by cytokine release. Why such reactions are confined selectively to the CSF compartment is unclear. Treatment includes discontinuation of the offending drug and a search for potential etiology of the meningitis. Patients should be treated with a third-generation cephalosporin if bacterial meningitis remains a possibility. Full recovery without sequelae is typical. Vogt-Koyanagi-Harada syndrome Exact etiology of this condition remains uncertain. Originally, the Vogt-Koyanagi syndrome was described independently of the Harada syndrome. However, the clinical manifestations of both overlap sufficiently to justify their combination into one single entity. Typically, it affects dark-skinned individuals or those of Asian races. Symptoms consist of impaired vision, headache, tinnitus, impaired hearing, photophobia, vertigo, vomiting, and seizures. Findings include alopecia, cavities, vitiligo, iridocyclitis, uveitis, and serous retinal detachments. Occasionally, elevated protein and pleocytosis have been found in the CSF. The disease usually occurs in the third decade of life and follows a recurrent course. Many neurological manifestations are believed to be secondary to adhesive arachnoiditis. Cranial nerve palsies and hemipareses may result. Confusion, psychosis, and seizures also have been reported.

Prednisone therapy in moderate to high doses improves this condition. Behet syndrome The cause of Behet syndrome remains uncertain. A triad of uveitis, painful oral ulcers, and genital ulcers characterizes this disease. Other manifestations include arthritis and thrombophlebitis. CNS manifestations occur in 18% of patients with Behet syndrome and include meningoencephalitis, benign intracranial hypertension, papilledema, brainstem lesions, cranial nerve palsies, spinal cord lesions, and mental status changes. Mollaret meningitis Mollaret meningitis is a rare form of recurrent meningitis originally described by Mollaret in 1944. According to Bryun, who further refined the clinical diagnostic criteria, the condition is characterized by (1) recurrent episodes of severe headache, meningismus, and fever; (2) CSF pleocytosis with large endothelial cells (ie, Mollaret cells), neutrophils, and lymphocytes; (3) recurrent attacks separated by symptom-free periods of weeks to months; (4) spontaneous remission of symptoms and signs; and (5) no known causative agent. Cases without fever, with increased CSF gamma globulin and transient neurological signs and symptoms, have been reported. Transient neurological abnormalities, including seizures, diplopia, pathologic reflexes, cranial nerve pareses, hallucinations, and coma, occur in as many as 50% of patients. Mollaret cells, considered by many to be the hallmark of Mollaret meningitis (although not pathognomonic), are observed early and may comprise 60-70% of cells in the CSF. These cells are usually present for only the first 24 hours and can be missed easily. After the first 24 hours, the CSF shows a lymphocytic predominance with cell counts usually less than 3000/mm3. Hypoglycorrhachia (ie, low CSF glucose concentration) is reported in one third of the patients. CSF protein usually is elevated mildly. Recent data suggest that HSV-2 and, less frequently, HSV-1 may be etiologic in some if not most cases of Mollaret meningitis. Hence, acyclovir (intravenous or oral) or valacyclovir (oral only) are worthy of consideration for both therapy and prophylaxis. BIBLIOGRAPHY Section 9 of 9 Author Information Introduction Overview And General Information Specific Causes Evaluation And Diagnosis Treatment Differential Diagnosis, Complications, Prognosis, And Prevention Related Conditions Bibliography