Reactive meningitis

According to the etiology, inflammation of the soft and arachnoid membranes of the brain (leptomeninges) - meningitis - can be bacterial, viral, parasitic or fungal. Or it could be non-infectious or reactive meningitis. 

Epidemiology

According to statistics, with systemic lupus erythematosus, non-infectious meningitis is observed in 1.4-2% of cases, with sarcoidosis - in 10%, and with blood cancers - in 5-15% of patients.

Causes of the reactive meningitis

Key causes of reactive  meningitis  include non-infectious autoimmune diseases, cancer, head trauma or brain surgery, a variety of pharmacological agents, and certain vaccines. [1], [2]

Similar are the risk factors for its development.

Meningitis of this type can develop:

• with  systemic lupus erythematosus  (SLE); [3], [4] 
• with  Behcet's disease  (systemic vasculitis); [5]
• in patients with  idiopathic thrombocytopenic purpura ;
• in cases of  sarcoidosis , and can be diagnosed as neurosarcoidosis in the form of chronic meningitis; [6], [7] 
• with melanoma, breast and gastrointestinal cancer, lung adenocarcinoma,  T-cell lymphoma  (non-Hodgkin's),  acute lymphoblastic leukemia in children . [8]

 The use of non-steroidal anti-inflammatory drugs (NSAIDs) can lead to the development of drug-induced  aseptic meningitis; fluoroquinolone antibiotic Ciprofloxacin, anti-tuberculosis antibiotic Isoniazid and sulfonamides; anticonvulsants Carbamazepine (Finlepsin) and Lamotrigine (Lamotrin); the immunosuppressant Azathioprine; medicines for the treatment of gastric ulcer (Ranitidine, Ranigast, Zantaka, etc.) or the treatment of gout (Allopurinol); some means for epidural anesthesia; anticancer drugs (Methotrexate, Pemetrexed, Cytarabine), as well as monoclonal antibodies (Infliximab, Adalimumab, Cetuximab). [9]

Pathogenesis

Patients with systemic lupus erythematosus are more likely to develop infections due to both immune problems and immunosuppressant therapy. At the same time, according to the results of studies, in 50% of cases, pathogenic bacteria in the cerebrospinal fluid (even in the presence of lymphocytic or neutrophilic pleocytosis) are not detected by microbiological methods, therefore meningitis is defined as aseptic.

Most often in SLE, the pathogenesis of reactive meningitis without revealing an infectious etiology is explained by non-inflammatory thickening of the endothelium of the vascular walls of the capillaries of the brain membrane in response to the action of autoantibodies circulating in the cerebrospinal fluid, which is defined as immune-mediated vasculopathy. In addition, it is suggested that lupus anticoagulant (a prothrombotic antibody that binds to phospholipids of cell membranes of blood platelets) can cause occlusion of small vessels with the development of chronic tissue hypoxia.

Also, the mechanism of damage to the meninges in lupus is seen in the effect on the choroid plexus of antigen-antibody complexes that penetrate the blood-brain barrier. And some experts believe that the whole thing is non-steroidal anti-inflammatory drugs and immunity-suppressing drugs taken for a long time with this autoimmune pathology.

In the presence of the previously named oncological diseases, non-infectious meningitis is a consequence of the spread of cancer cells to the meninges, and it can be defined as neoplastic meningitis, meningeal or leptomeningeal  carcinomatosis .

In cases of drug-induced reactive meningitis, the mechanism of alteration of the meninges can be associated both with reactions of increased autoimmune sensitivity to the active substances of pharmacological drugs, and with their side effects.

Symptoms of the reactive meningitis

The first signs of reactive meningitis may be intense headaches and fever.

In general, its symptoms are typical of meningitis and include: stiffness (stiffness) of the muscles of the neck, nausea and vomiting, increased sensitivity of the eyes to light (photophobia), and changes in mental state in the form of confusion.

Reactive meningitis in a newborn may manifest itself only with nonspecific symptoms (increased irritability or drowsiness).

In addition to headache, hydrocephalus, swallowing problems, and cranial nerve palsies may be common in neoplastic meningitis.

Drug-induced reactive meningitis usually shows neurological symptoms such as numbness, paresthesias, and seizures.

Complications and consequences

This type of meningitis can lead to serious complications (such as deafness or hydrocephalus) as well as long-term consequences such as epilepsy or cognitive impairment.

Diagnostics of the reactive meningitis

Diagnosis of reactive or non-infectious meningitis is carried out in a complex manner and is based on clinical symptoms, laboratory tests and hardware imaging.

Analyzes include cytological and  general analysis of cerebrospinal fluid  (CSF), as well as bakposev or PCR blood test.

Instrumental diagnostics uses  magnetic resonance imaging (MRI) of the brain .

Differential diagnosis

The differential diagnosis should rule out bacterial and other types of infectious meningitis, as well as  meningismus .

Treatment of the reactive meningitis

Treatment options may vary depending on the specific cause of meningitis.

In cases of non-infectious (reactive) meningitis, treatment is directed at the causative disease, meaning treatment options vary.

Stop taking drugs that cause an increased response with alteration of the meninges.

Supportive care is also given to reduce the intensity of symptoms.

In addition, in a serious condition of patients - until the results of the CSF analysis are obtained, antibacterial drugs and corticosteroids are urgently used preventively. They are canceled if the cerebrospinal fluid is sterile, that is, after the exclusion of infectious causes.

For patients with leptomeningeal carcinomatosis, a combination of radiation therapy and chemotherapy (with the introduction of an anticancer drug into the cerebrospinal fluid by lumbar puncture) is indicated.

Prevention

Currently, the prevention of the development of reactive meningitis can only concern the prescription and use of drugs that may be involved in its occurrence, as well as monitoring the condition of patients in the treatment of which such medications are used.

Forecast

The prognosis of the outcome of non-infectious meningitis depends on the disease that provoked it. For example, most patients with neoplastic reactive meningitis, if untreated, live for one to one and a half months, dying due to progressive neurological dysfunction; with therapy, survival is three to six months.