Aseptic meningitis

Aseptic meningitis is an inflammation of the meninges with lymphocytic pleocytosis in the cerebrospinal fluid in the absence of a pathogen according to the results of a biochemical bacteriological study of the CSF.

The most common cause of aseptic meningitis is viruses, other causes may be infectious or non-infectious. The disease manifests itself with fever, headache and meningeal symptoms. Aseptic meningitis of viral etiology usually resolves on its own. Treatment is symptomatic.

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What causes aseptic meningitis?

Aseptic meningitis develops under the influence of infectious (for example, rickettsia, spirochetes, parasites) and non-infectious causes (for example, intracranial tumors and cysts, chemotherapy drugs, systemic diseases).

Enteroviruses, primarily ECHO and Coxsackie viruses, are the predominant causative agents. Mumps is a common causative agent in many countries; it has become rare in the United States due to vaccination programs. Enteroviruses and mumps are acquired via the respiratory or gastrointestinal tract and disseminated hematogenously. Mollaret meningitis is a benign serous recurrent meningitis characterized by the presence of large atypical monocytes (previously thought to be endothelial cells) in the CSF; herpes simplex virus type II or other viruses are thought to be the cause. Viruses that cause encephalitis usually also cause mild serous meningitis.

Some bacteria, in particular spirochetes (causative agents of syphilis, Lyme borreliosis and leptospirosis) and rickettsia (causative agents of typhus, Rocky Mountain spotted fever and ehrlichiosis) can also act as causative agents of aseptic meningitis. Pathological changes in the CSF can be transient or persistent. In a number of bacterial infectious diseases - mastoiditis, sinusitis, brain abscess and infective endocarditis - reactive changes in the cerebrospinal fluid characteristic of aseptic meningitis are observed. This occurs due to the fact that the generalized inflammatory process induces the development of systemic vasculitis and reactive pleocytosis in the CSF even in the absence of bacteria.

Causes of aseptic meningitis

Infection	Examples
Bacterial	Brucellosis, cat scratch disease, cerebral Whipple's disease, leptospirosis, Lyme disease (neuroborreliosis), lymphogranuloma venereum, mycoplasma infection, rickettsial infection, syphilis, tuberculosis
Post-infectious hypersensitivity reactions	Possible for many viral infections (eg, measles, rubella, smallpox, cowpox, chickenpox)
Viral	Chickenpox; Coxsackie virus, ECHO virus; Polio; West Nile fever; Eastern and Western equine encephalitis; Herpes simplex virus; HIV infection, cytomegalovirus infection; Infectious hepatitis; Infectious mononucleosis; Lymphocytic choriomeningitis; Mumps; St. Louis encephalitis
Fungal and parasitic	Amebiasis, coccidioidomycosis, cryptococcosis, malaria, neurocysticercosis, toxoplasmosis, trichinosis

Non-infectious

Medicines	Azathioprine, carbamazepine, ciprofloxacin, cytosine arabinoside (high dose), immunoglobulin, muromonab CD3, isoniazid, NSAIDs (ibuprofen, naproxen, sulindac, tolmetin), monoclonal antibody 0KT3, penicillin, phenazopyridine, ranitidine, trimethoprim-sulfamethoxazole
Lesions of the meninges	Behcet's disease with nervous system involvement, leakage of intracranial epidermoid tumor or craniopharyngioma effusion into CSF, meningeal leukemia, tumors of the dura mater, sarcoidosis
Parameningeal processes	Brain tumor, chronic sinusitis or otitis, multiple sclerosis, stroke
Reaction to endolumbar drug administration	Air, antibiotics, chemotherapeutic drugs, spinal anesthetics, iophendilate, other dyes
Reaction to the introduction of the vaccine	For many, especially for whooping cough, rabies and smallpox
Other	Lead meningitis, Mollaret meningitis

"Aseptic" in this context refers to cases in which bacteria are not detected by routine bacterioscopy and culture. These cases include some bacterial infections.

Fungi and protozoa can cause purulent meningitis with the development of sepsis and changes in the cerebrospinal fluid, characteristic of bacterial meningitis, with the difference that the pathogens are not detected by bacterioscopy of a stained smear and are therefore classified in this category.

Non-infectious causes of meningeal inflammation include tumor infiltration, rupture of intracranial cyst contents into the cerebrospinal fluid circulation, endolumbar drug administration, lead poisoning, and irritation with contrast agents. Reactive inflammation may develop as a hypersensitivity reaction to systemic drug administration. The most common hypersensitivity reactions are caused by NSAIDs (especially ibuprofen), antimicrobials (especially sulfonamides), and immunomodulators (intravenous immunoglobulins, monoclonal antibodies, cyclosporine, vaccines).

Symptoms of aseptic meningitis

Aseptic meningitis following premorbid flu-like syndrome (without runny nose) is manifested by fever and headache. Meningeal signs are less pronounced and develop more slowly than in acute bacterial meningitis. The general condition of the patient is satisfactory, systemic or non-specific symptoms predominate. Focal neurological symptoms are absent. In patients with non-infectious inflammation of the meninges, body temperature is usually normal.

Diagnosis of aseptic meningitis

Aseptic meningitis is suspected in the presence of fever, headache, and meningeal symptoms. Before performing a lumbar puncture, it is necessary to perform CT or MRI of the skull, especially if a space-occupying intracranial process is suspected (in the presence of focal neurological symptoms or optic disc edema). Changes in the CSF in aseptic meningitis are reduced to a moderate or significant increase in intracranial pressure and lymphocytic pleocytosis in the range from 10 to more than 1000 cells / μl. At the very beginning of the disease, a small number of neutrophils can be detected. The concentration of glucose in the CSF is within normal limits, protein is within normal limits or moderately increased. To identify the virus, PCR is performed with a CSF sample, in particular, Mollaret's meningitis is confirmed by detecting DNA of the herpes simplex virus type II in the CSF sample. Reactive aseptic meningitis to the administration of drugs is a diagnosis of exclusion. The diagnostic algorithm is formed based on clinical and anamnestic data, which involves a targeted search among a number of possible pathogens (rickettsiosis, Lyme borreliosis, syphilis, etc.).

Differential diagnosis of bacterial meningitis, which requires urgent specific treatment, and aseptic meningitis, which does not, is sometimes problematic. Detection of even minor neutrophilia in the cerebrospinal fluid, which is acceptable in the early stage of viral meningitis, should be interpreted in favor of the early stage of bacterial meningitis. CSF parameters are also similar in cases of partially treated bacterial meningitis and aseptic meningitis. Representatives of Listeria spp., on the one hand, are practically not identified by bacterioscopy of a Gram-stained smear, but on the other hand, they induce a monocytic reaction in the cerebrospinal fluid, which should be interpreted rather in favor of aseptic than bacterial meningitis. It is well known that the tubercle bacillus is very difficult to detect bacterioscopically and that changes in cerebrospinal fluid parameters in tuberculosis are almost identical to changes in aseptic meningitis; However, to verify the diagnosis of tuberculous meningitis, they rely on the results of a clinical examination, as well as an elevated protein level and a moderately reduced glucose concentration in the CSF. Sometimes, idiopathic intracranial hypertension debuts under the guise of aseptic meningitis.

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Treatment of aseptic meningitis

In most cases, the diagnosis of aseptic meningitis is obvious, the therapeutic algorithm includes mandatory rehydration, pain relief and antipyretic drugs. If the examination fails to completely exclude the possibility of listeriosis, partially treated or early bacterial meningitis, the patient is prescribed antibiotics effective against traditional pathogens of bacterial meningitis until the final results of the cerebrospinal fluid test are obtained. In the case of reactive aseptic meningitis, discontinuing the causative drug usually leads to rapid relief of symptoms. Acyclovir is prescribed for the treatment of Mollaret meningitis.