Tuberculous meningitis, also known as TB meningitis or tubercular meningitis, is a specific type of bacterial

meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, intense headache, vomiting and neck stiffness and occasion ...

caused by the ''

Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb), also known as Koch's bacillus, is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' ha ...

'' infection of the

meninges In anatomy, the meninges (; meninx ; ) are the three membranes that envelop the brain and spinal cord. In mammals, the meninges are the dura mater, the arachnoid mater, and the pia mater. Cerebrospinal fluid is located in the subarachnoid spac ...

—the system of membranes which envelop the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

Signs and symptoms

Fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...

and

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

are the cardinal features; confusion is a late feature and

coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to Nociception, respond normally to Pain, painful stimuli, light, or sound, lacks a normal Circadian rhythm, sleep-wake cycle and does not initiate ...

bears a poor prognosis. Meningism is absent in a fifth of patients with TB meningitis. Patients may also have focal neurological deficits.

Causes

'' of the meninges is the cardinal feature and the inflammation is concentrated towards the base of the

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

. When the inflammation is in the

brain stem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is co ...

subarachnoid area,

cranial nerve Cranial nerves are the nerves that emerge directly from the brain (including the brainstem), of which there are conventionally considered twelve pairs. Cranial nerves relay information between the brain and parts of the body, primarily to and f ...

roots may be affected. The symptoms will mimic those of space-occupying lesions. Blood-borne spread certainly occurs, presumably by crossing the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

, but a proportion of patients may get TB meningitis from rupture of a cortical focus in the brain; an even smaller proportion get it from rupture of a bony focus in the spine.

Pathophysiology

The pathophysiology of tuberculous meningitis involves bacterial invasion of the brain

parenchyma upright=1.6, Lung parenchyma showing damage due to large subpleural bullae. Parenchyma () is the bulk of functional substance in an animal organ such as the brain or lungs, or a structure such as a tumour. In zoology, it is the tissue that ...

meninges or cortex, causing the formation of small subpial foci. These foci, termed Rich foci, are necrotic and expand as the colonies within them multiply. Tubercle (focal) rupture in the

subarachnoid In anatomy, the meninges (; meninx ; ) are the three membranes that envelop the brain and spinal cord. In mammals, the meninges are the dura mater, the arachnoid mater, and the pia mater. Cerebrospinal fluid is located in the subarachnoid sp ...

space causes meningitis.

Diagnosis

Diagnosis of TB meningitis is made by analysing

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ven ...

collected by lumbar puncture. When collecting CSF for suspected TB meningitis, a minimum of 1 ml of fluid should be taken (preferably 5 to 10 ml). The CSF usually has a high protein, low glucose and a raised number of lymphocytes.

Acid-fast bacilli Acid-fastness is a physical property of certain bacterial and Eukaryote, eukaryotic cell (biology), cells, as well as some Sub-cellular, sub-cellular structures, specifically their resistance to decolorization by acids during laboratory staining p ...

are sometimes seen on a CSF smear, but more commonly, ''M. tuberculosis'' is grown in culture. A spiderweb clot in the CSF that has been collected is rare but indicative of TB meningitis. ELISPOT testing is not useful for the diagnosis of acute TB meningitis and is often false negative, but may paradoxically become positive after treatment has started, which helps to confirm the diagnosis.

Nucleic acid amplification tests (NAAT)

This is a group of tests that use

polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to make millions to billions of copies of a specific DNA sample rapidly, allowing scientists to amplify a very small sample of DNA (or a part of it) sufficiently to enable detailed st ...

(PCR) to detect mycobacterial nucleic acid. These test vary in which nucleic acid sequence they detect and vary in their accuracy. The two most common commercially available tests are the amplified mycobacterium tuberculosis direct test (MTD, Gen-Probe) and Amplicor. In 2007, review concluded that for diagnosing tuberculous meningitis "Individually, the AMTD test appears to perform the best (sensitivity 74% and specificity 98%)", they found the pooled prevalence of TB meningitis to be 29%. The fully automated PCR test using the Cepheid GeneXpert system of the Xpert Ultra MTB/RIF has improved sensitivity of up to 77% in persons with HIV and TB meningitis.

Treatment

The treatment of TB meningitis is

isoniazid Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the treatment of tuberculosis. For active tuberculosis, it is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol. F ...

, rifampicin,

pyrazinamide Pyrazinamide is a medication used to treat tuberculosis. For active tuberculosis, it is often used with rifampicin, isoniazid, and either streptomycin or ethambutol. It is not generally recommended for the treatment of latent tuberculosis. It i ...

and

ethambutol Ethambutol (EMB, E) is a medication primarily used to treat tuberculosis. It is usually given in combination with other tuberculosis medications, such as isoniazid, rifampicin and pyrazinamide. It may also be used to treat ''Mycobacterium avi ...

for two months, followed by isoniazid and rifampicin alone for a further ten months. Steroids help reduce the risk of death in those without HIV. Steroids can be used in the first six weeks of treatment, A few people may require

immunomodulator Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...

y agents such as

thalidomide Thalidomide, sold under the brand names Contergan and Thalomid among others, is an oral administered medication used to treat a number of cancers (e.g., multiple myeloma), graft-versus-host disease, and many skin disorders (e.g., complication ...

Hydrocephalus Hydrocephalus is a condition in which cerebrospinal fluid (CSF) builds up within the brain, which can cause pressure to increase in the skull. Symptoms may vary according to age. Headaches and double vision are common. Elderly adults with n ...

occurs as a complication in about a third of people with TB meningitis. The addition of aspirin may reduce or delay mortality, possibly by reducing complications such as cerebral infarctions.

References

External links

{{DEFAULTSORT:Tuberculous Meningitis Tuberculosis Meningitis