Aseptic meningitis
You don't need to be Editor-In-Chief to add or edit content to WikiDoc. You can begin to add to or edit text on this WikiDoc page by clicking on the edit button at the top of this page. Next enter or edit the information that you would like to appear here. Once you are done editing, scroll down and click the Save page button at the bottom of the page.
| Aseptic meningitis Classification and external resources | |
| ICD-10 | G03. Nonpyogenic meningitis |
|---|---|
| ICD-9 | 322.0 Nonpyogenic menigitis |
| DiseasesDB | 945 |
| eMedicine | NEURO/697 |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-525-6884
Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2] Phone:617-525-7431
Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [3] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
Synonyms and Key words: Viral meningitis
Aseptic meningitis is a condition in which the layers lining of the brain, or meninges, become inflamed and a pyogenic bacterial source is not to blame. Meningitis is diagnosed on a history of characteristic symptoms and certain examination findings (e.g. Kernig's sign). Investigations should show an increase in the number of leukocytes present in the cerebrospinal fluid (CSF), obtained via lumbar puncture, (normal being fewer than five visible per microscopic high power field).
The term aseptic is frequently a misnomer, implying a lack of infection. On the contrary, many cases of aseptic meningitis represent infection with viruses or mycobacteria that cannot be detected with routine methods. While the advent of polymerase chain reaction has increased the ability of clinicians to detect viruses such as enterovirus, cytomegalovirus, and herpes virus in the CSF, many viruses can still escape detection. Additionally, mycobacteria frequently require special stains and culture methods that make their detection difficult. When CSF findings are consistent with meningitis, and microbiologic testing is unrevealing, clinicians typically assign the diagnosis of aseptic meningitis—making it a relative diagnosis of exclusion.
Aseptic meningitis can result from non-infectious causes; it is a relatively infrequent side effect of medications, and can be an early finding in autoimmune disease.
Nomenclature
Wallgren coined the term aseptic meningitis in 1925 and defined it as a disease with acute onset that had typical systematic symptoms of meningeal involvement, in association with a cerebrospinal fluid (CSF) typical of meningitis (typically with a mononuclear cell predominance). Additionally, there was absence of bacteria on stain and culture and there was no identifiable parameningeal infection. Patients typically had a relatively short and benign course. Other terms sometimes included in the umbrella ‘aseptic meningitis’ (AM) are lymphocytic, viral, chemical, non-bacterial and sterile. Currently, the term AM is used to describe patients with no detectable bacterial cause after initial CSF evaluation. Unfortunately, it is often difficult to predict who will have a life-threatening disease from those who will rapidly recover without specific treatment.
Epidemiology and Demographics
Aseptic meningitis is relatively common, with an incidence of around 10/100,000. The male:female ratio is around 1:1.
There are approximately 8,300 – 12,700 cases of AM / year in the U.S., however this is likely a gross underestimate due to underreporting.
- There is a marked seasonal variability, similar to that of enterovirus, which is the most commonly diagnosed cause of AM.
Classification
There is no formal classification system. It is usually by the causative organism if identified.
Pathophysiology
Invasion into or past the meninges by a pathogen can set up a local inflammatory response. The clinical signs are due to this meningeal irritation - for example, Kernig's sign is due to pain produced by stretching of the inflamed meninges.
Many different viruses can cause meningitis. About 90% of cases of viral meningitis are caused by members of a group of viruses known as enteroviruses, such as coxsackieviruses and echoviruses. These viruses are more common during summer and fall months. Herpesviruses and the mumps virus can also cause viral meningitis.
The study of AM is complicated in that there can be a yearly variation in the viruses that are prevalent, as well as differences in geography, diagnostic techniques and the definition of AM.
- One study (from 1960, in the U.S, Europe and the Far East) reported that out of 430 cases of AM, a specific cause was found in 71%.
- 42% had enterovirus, 22% mumps, 12% poliovirus, 12% lymphocytic choriomeningitis virus, 5% leptospirosis, 2% herpes simplex, 1% arboviruses and <1% had Tuberculosis (TB).
- If a study like this were to be repeated today, there would obviously be an increase in HIV and Lyme disease (as well as other previously unrecognized causes of AM such as epidural steroid injection and drugs) and a fall in polio and mumps.
- Enteroviruses currently are thought to account for > 80% of identifiable cases of AM.
- This group (members of the picornavirus family) includes coxsackievirus A&B, echovirus, enterovirus, hepatitis A and poliovirus.
- Transmission is fecal – oral, and the viruses have a worldwide distribution.
- Although disease can occur year-round, it peaks in the summer and early fall.
- Children tend to be affected more commonly than adults, though community and hospital outbreaks can also occur.
- In addition to the typical presentation of meningitis, patients also tend to have viral exanthems, and may get myopericarditis, conjunctivitis and other typical enteroviral syndromes (i.e. hand-foot and mouth disease).
- The CSF is typically not helpful and diagnosis typically depends upon identification of the viral antigen by ELISA (enzyme-linked immunosorbent assay).
- Rx is supportive and the majority of patients do well.
- In countries that don’t have the polio vaccine, 90% of cases are clinically insignificant, 4-8% will get AM (non-paralytic polio) and < 1% will develop paralytic poliomyelitis.
- Mumps: a paramyxovirus that is spread via respiratory droplets, direct contact and by fomites.
- Although the incidence in the U.S. had dropped by 95% since the development of the vaccine, it continues to be a major problem worldwide with ~ 1 – 10% of infected patients developing AM.
- Again, although it can be seen year round, it most commonly occurs in the late winter and spring.
- Mumps should be specifically suspected when AM follows parotitis, orchitis, oophoritis and pancreatitis.
- Diagnosis is by culture and the prognosis tends to be excellent.
- Lymphocytic choriomeningitis virus (LCM) is an arenavirus that is spread to humans via contact with rodents or their excrement.
- LCM AM peaks in the late-fall and early winter, and diagnosis is made via chest x-ray or by seeing a fourfold rise in antibody titer between acute and convalescent sera.
- Herpes simplex virus (HSV) is the most common cause fatal encephalitis in the U.S. and it is crucial to differentiate meningitis from encephalitis.
- As opposed to encephalitis, which is usually due to HSV-1, meningitis is more frequently caused by HSV-2.
- The diagnosis is usually clinical (occasionally seen in patients with genital lesions) but the virus can be Cx from the CSF or buffy coat.
- The prognosis is generally quite good, and it is not clear whether prescription alters the course for mild cases.
- Human immunodeficiency virus (HIV) is an increasingly recognized cause of AM.
- AM can occur during initial infection as well as during seroconversion.
- Additionally, HIV can cause recurrent and chronic meningitis, occasionally with cranial nerve abnormalities (esp. V, VII, and VIII).
- Diagnosis can be made via CSF Cx and polymerase chain reaction (PCR) for viral DNA, though availability is limited.
- Arboviruses typically cause encephalitis, but in their milder forms can cause AM.
- The most likely of these to present as AM is St. Louis encephalitis, and all typically occur during the warmer months.
- Diagnosis is made serologically, and is mainly important as a public health measure.
- Prescription is supportive.
- Other, non-viral infectious causes include:
- TB: had CN abnormalities in 20 – 30% and is often accompanied by SIADH (inappropriate secretion of antidiuretic hormone), altered MS (multiple sclerosis) and a reduced CSF glucose.
- Mycoplasma pneumoniae.
- Listeria monocytogenes: often thought to be aseptic due to a negative gram stain and a slightly higher frequency of a CSF lymphocytosis.
- Brucellosis: causes neuro disease in < 5% of cases but AM is the most common
- Leptospirosis, Borrelia, and fungal meningitis (especially crypto, but also cocci and histo) can also be seen.
- The list of non-infectious causes of AM is huge:
- Sarcoidosis, SLE (systemic lupus erythematosus) and Behçet's disease are the most common systemic illnesses to be associated with AM.
Enteroviruses, the most common cause of viral meningitis, are most often spread through direct contact with respiratory secretions (e.g., saliva, sputum, or nasal mucus) of an infected person. This usually happens by shaking hands with an infected person or touching something they have handled, and then rubbing your own nose or mouth. The virus can also be found in the stool of persons who are infected. The virus is spread through this route mainly among small children who are not yet toilet trained. It can also be spread this way to adults changing the diapers of an infected infant. The incubation period for enteroviruses is usually between 3 and 7 days from the time you are infected until you develop symptoms. You can usually spread the virus to someone else beginning about 3 days after you are infected until about 10 days after you develop symptoms.
Risk Factors
The viruses that cause viral meningitis are contagious. Enteroviruses, for example, are very common during the summer and early fall, and many people are exposed to them. However, most infected persons either have no symptoms or develop only a cold or rash with low-grade fever. Only a small proportion of infected persons actually develop meningitis. Therefore, if you are around someone who has viral meningitis, you have a moderate chance of becoming infected, but a very small chance of developing meningitis.
Causes
The cause can be infectious or non-infectious.
Infectious
Viruses
- HSV 1 and 2
- HIV
- Enteroviruses
- Varicella zoster
- Epstein-Barr virus
- CMV
- Lymphocytic choriomeningitis virus
Bacteria
- Partially treated meningitis
- Endocarditis
- Mycoplasma
- Mycobacterium tuberculosis
- Borrelia burgdorferi
- Treponema pallidum
- Brucella
Fungi
- Cryptococcus neoformans
- Blastomyces dermatitidis
Parasites
Non-infectious
Drugs
Systemic Diseases
Miscellaneous
Diagnosis
Our main task is to identify bacterial or other treatable causes of meningitis as well as to decide if empiric antibiotic / antiviral therapy is necessary. Additionally, we should be able to identify benign etiologies in order to prevent unnecessary testing / treatment. The history should focus on exact details of disease onset and associated Sx as well as PMH (including immunosuppression), travel, exposure to animals, insects and their excrement, and HIV risk factors. One should also consider likely etiologies depending upon geography and time of year. Spanos et.al. developed a predictive model based on age, month, CSF/serum glucose ratio and the CSF poly count. [1] [1] [1] [1]
- As rough guidelines go, AM tends to have a CSF WBC count < 500 (though > several thousand can be seen) with a mononuclear cell predominance. The protein is generally normal (can be high) and glucose is usually normal.
- PMNs can predominate in the 1st 48h in up to 2/3 of patients.
- Other lab tests, such as the C-reactive protein, the Limulus lysate assay, LDH etc. have been looked at, but are generally not recommended due to their poor sensitivity and specificity.
- Unfortunately, there are no formal recommendations for which treatment for bacterial processes can be withheld and therefore Rx needs to be individualized.
Symptoms and Signs
These are varied, depending on the causative organism. There are usually non-specific constitutional symptoms lasting for hours or days. These are then followed by meningitis, characterised by headache, stiff neck, fever, photophobia, drowsiness, and myalgia. A rash may be present, which could suggest a particular virus - for example, varicella zoster. However, a non-blanching purpuric rash is not associated with meningitis and suggests systemic bacterial infection.
The more common symptoms of meningitis are fever, severe headache, stiff neck, bright lights hurting the eyes, drowsiness or confusion, and nausea and vomiting. In babies, the symptoms are more difficult to identify. They may include fever, fretfulness or irritability, difficulty in awakening the baby, or the baby refuses to eat. The symptoms of meningitis may not be the same for every person.
Laboratory Tests
Usually the history and examination will arouse suspicion. Confirmation is mainly through CSF findings:
- Less than 500 mononuclear cells/mm³ (pleocytosis) should develop with 8-48 hours
- Normal glucose
- Elevated pressure
- Elevated protein
- No findings which suggest another diagnosis - e.g. negative bacteria antigen tests, no lactate
- PCR may identify a causative organism
Viruses may be cultured from swabs of other areas, such as the throat.
Blood tests are rarely helpful in establishing the diagnosis (but may be of use to establish baseline chemistry). Imaging is useful in excluding other diagnoses, or identifying other features of infection by an organsim - for example, a chest X-ray may be useful if tuberculosis is suspected.
Treatment
No specific treatment for viral meningitis exists at this time. Most patients completely recover on their own. Doctors often will recommend bed rest, plenty of fluids, and medicine to relieve fever and headache.
Anti-pathogenic
If the causative organism has been identified and has a specific therapy, this should be started.
Bacteria
Even though true aseptic meningitis cannot be caused by pyogenic bacteria, broad-spectrum antibiotic cover should be started as the consequences of misdiagnosing a bacterial meningitis are dire, and relatively easily avoided. For non-pyogenic bacteria, local sensitivities should be taken into account, but generally broad-spectrum is best. Some bacteria are normally sensitive to certain drugs - for example, rifampicin is good for Brucella.
Viruses
HSV, varicella and CMV have a specific antiviral therapy; most other viruses do not. For HSV the treatment of choice is acyclovir[1]
Fungi
Amphotericin B and fluconazole are the best antifungals in most situations.
Supportive
This will be the majority of the treatment. Fluids, analgesia and antiemetics should cover most cases. Antipyretics should be used judiciously - fever can be a natural response. Steroids are not recommended unless raised intracranial pressure occurs. Phenytoin and other anticonvulsants can be used is seizures occur, but prophylaxis is not recommended.
Complications
Seizures, encephalitis and cognitive problems can develop, although rarely.
Prognosis
In immunocompetent individuals, the disease is usually mild and self-limiting. Full recovery 5-14 days afterwards is normal.
Prevention/Screening
Vaccines are available for some organisms that cause aseptic menigitis. Good infection control in hospital, as ever, is recommended. If the causative organism is contagious, steps may need to be taken to isolate the individual and protect the community.
Primary Prevention
Because most persons who are infected with enteroviruses do not become sick, it can be difficult to prevent the spread of the virus. However, adhering to good personal hygiene can help to reduce your chances of becoming infected. If you are in contact with someone who has viral meningitis, the most effective method of prevention is to wash your hands thoroughly and often. Also, cleaning contaminated surfaces and soiled articles first with soap and water, and then disinfecting them with a dilute solution of chlorine-containing bleach (made by mixing approximately ¼ cup of bleach with 1 gallon of water) can be a very effective way to inactivate the virus, especially in institutional settings such as child care centers.
References
Health science > Medicine | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Specialties and Subspecialties |
| ||||||||||||||||
| Other | |||||||||||||||||
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
