Tuberculous meningitis
Encyclopedia
Tuberculous meningitis is also known as TB meningitis or tubercular meningitis.
Tuberculous meningitis
is Mycobacterium tuberculosis
infection of the meninges
—the system of membrane
s which envelops the central nervous system
. It is the most common form of CNS
tuberculosis
.
and headache
are the cardinal features. Confusion
is a late feature and coma
bears a poor prognosis. Meningism
is absent in a fifth of patients with TB meningitis. Patients may also have focal neurological deficits.
of the meninges is the cardinal feature and the inflammation is concentrated towards the base of the brain. When the inflammation is in the brain stem subarachnoid area, cranial nerve roots may be affected. The symptoms will mimic those of space-occupying lesions. Infection begins in the lungs and may spread to the meninges by a variety of routes.
Blood-borne spread certainly occurs and 25% of patients with miliary TB have TB meningitis, presumably by crossing the blood-brain barrier
; but a proportion of patients may get TB meningitis from rupture of a cortical focus in the brain (a so-called Rich focus
); an even smaller proportion get it from rupture of a bony focus in the spine. It is rare and unusual for TB of the spine to cause TB of the central nervous system
, but isolated cases have been described.
collected by lumbar puncture
. When collecting CSF for suspected TB meningitis, a minimum of 1ml of fluid should be taken (preferably 5 to 10ml).
The CSF usually has a high protein, low glucose and a raised number of lymphocytes. Acid-fast bacilli are sometimes seen on a CSF smear, but more commonly, M. tuberculosis is grown in culture. A spiderweb clot in the collected CSF is characteristic of TB meningitis, but is a rare finding.
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.
More than half of cases of TB meningitis cannot be confirmed microbiologically, and these patients are treated on the basis of clinical suspicion only. The culture of TB from CSF takes a minimum of two weeks, and therefore the majority of patients with TB meningitis are started on treatment before the diagnosis is confirmed.
(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, a systematic review of NAAT by the NHS Health Technology Assessment Programme concluded that for diagnosing tuberculous meningitis "Individually, the AMTD test appears to perform the best (sensitivity 74% and specificity 98%) [page 87]" . In the NHS meta-analysis
, they found the pooled prevalence of TB meningitis to be 29% [page 85]; however there was much heterogeneity in the reported sensitivities. Using a clinical calculator, these numbers yield a positive predictive value
of 94% and a negative predictive value
of 90%; however the 30% prevalence may be high due to referral bias. Alternate estimates of disease prevalence can be entered into the clinical calculator to refine the predictive values.These intcances vary from patient to patient according to their pathology.
or MRI
may show features strongly suggestive of TB meningitis, but cannot diagnose it.
The treatment of TB meningitis is isoniazid
, rifampicin
, pyrazinamide
and ethambutol
for two months, followed by isoniazid and rifampicin alone for a further ten months. Steroids are always used in the first six weeks of treatment (and sometimes for longer). A few patients may require immunomodulator
y agents such as thalidomide
.
Treatment must be started as soon as there is a reasonable suspicion of the diagnosis. Treatment must not be delayed while waiting for confirmation of the diagnosis.
Hydrocephalus
occurs as a complication in about a third of patients with TB meningitis and will require a ventricular shunt. The addition of aspirin may improve mortality, possibly by reducing complications such as infarcts.
Tuberculous meningitis
Meningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...
is Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...
infection of the meninges
Meninges
The meninges is the system of membranes which envelopes the central nervous system. The meninges consist of three layers: the dura mater, the arachnoid mater, and the pia mater. The primary function of the meninges and of the cerebrospinal fluid is to protect the central nervous system.-Dura...
—the system of membrane
Mesothelium
The mesothelium is a membrane that forms the lining of several body cavities: the pleura , peritoneum and pericardium . Mesothelial tissue also surrounds the male internal reproductive organs and covers the internal reproductive organs of women...
s which envelops the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
. It is the most common form of CNS
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
.
Clinical features
FeverFever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
and headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
are the cardinal features. Confusion
ConFusion
ConFusion is an annual science fiction convention organized by the Stilyagi Air Corps and its parent organization, the Ann Arbor Science Fiction Association. Commonly, it is held the third weekend of January. It is the oldest science fiction convention in Michigan, a regional, general SF con...
is a late feature and coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
bears a poor prognosis. Meningism
Meningism
Meningism is the triad of nuchal rigidity , photophobia and headache. It is a sign of irritation of the meninges, such as seen in meningitis, subarachnoid hemorrhages and various other diseases...
is absent in a fifth of patients with TB meningitis. Patients may also have focal neurological deficits.
Pathology
Mycobacterium tuberculosisMycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...
of the meninges is the cardinal feature and the inflammation is concentrated towards the base of the brain. When the inflammation is in the brain stem subarachnoid area, cranial nerve roots may be affected. The symptoms will mimic those of space-occupying lesions. Infection begins in the lungs and may spread to the meninges by a variety of routes.
Blood-borne spread certainly occurs and 25% of patients with miliary TB have TB meningitis, presumably by crossing the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
; but a proportion of patients may get TB meningitis from rupture of a cortical focus in the brain (a so-called Rich focus
Rich focus
A Rich focus is a tuberculous granuloma occurring on the cortex of the brain that ruptures into the subarachnoid space, causing tuberculous meningitis.It is named for Arnold Rice Rich who first described it....
); an even smaller proportion get it from rupture of a bony focus in the spine. It is rare and unusual for TB of the spine to cause TB of the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
, but isolated cases have been described.
Diagnosis
Diagnosis of TB meningitis is made by analysing cerebrospinal fluidCerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
collected by lumbar puncture
Lumbar puncture
A lumbar puncture is a diagnostic and at times therapeutic procedure that is performed in order to collect a sample of cerebrospinal fluid for biochemical, microbiological, and cytological analysis, or very rarely as a treatment to relieve increased intracranial pressure.-Indications:The...
. When collecting CSF for suspected TB meningitis, a minimum of 1ml of fluid should be taken (preferably 5 to 10ml).
The CSF usually has a high protein, low glucose and a raised number of lymphocytes. Acid-fast bacilli are sometimes seen on a CSF smear, but more commonly, M. tuberculosis is grown in culture. A spiderweb clot in the collected CSF is characteristic of TB meningitis, but is a rare finding.
ELISPOT
ELISPOT
The Enzyme-linked immunosorbent spot assay is a common method for monitoring immune responses in humans and animals. It was developed by Cecil Czerkinsky in 1983....
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.
More than half of cases of TB meningitis cannot be confirmed microbiologically, and these patients are treated on the basis of clinical suspicion only. The culture of TB from CSF takes a minimum of two weeks, and therefore the majority of patients with TB meningitis are started on treatment before the diagnosis is confirmed.
Nucleic acid amplification tests (NAAT)
This is a heterogeneous group of tests that use polymerase chain reactionPolymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....
(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, a systematic review of NAAT by the NHS Health Technology Assessment Programme concluded that for diagnosing tuberculous meningitis "Individually, the AMTD test appears to perform the best (sensitivity 74% and specificity 98%) [page 87]" . In the NHS meta-analysis
Meta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...
, they found the pooled prevalence of TB meningitis to be 29% [page 85]; however there was much heterogeneity in the reported sensitivities. Using a clinical calculator, these numbers yield a positive predictive value
Positive predictive value
In statistics and diagnostic testing, the positive predictive value, or precision rate is the proportion of subjects with positive test results who are correctly diagnosed. It is a critical measure of the performance of a diagnostic method, as it reflects the probability that a positive test...
of 94% and a negative predictive value
Negative predictive value
In statistics and diagnostic testing, the negative predictive value is a summary statistic used to describe the performance of a diagnostic testing procedure. It is defined as the proportion of subjects with a negative test result who are correctly diagnosed. A high NPV means that when the test...
of 90%; however the 30% prevalence may be high due to referral bias. Alternate estimates of disease prevalence can be entered into the clinical calculator to refine the predictive values.These intcances vary from patient to patient according to their pathology.
Imaging
Imaging studies such as CTComputed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
or MRI
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
may show features strongly suggestive of TB meningitis, but cannot diagnose it.
Treatment
See: tuberculosis treatmentTuberculosis treatment
Tuberculosis treatment refers to the medical treatment of the infectious disease tuberculosis .The standard "short" course treatment for TB is isoniazid, rifampicin , pyrazinamide, and ethambutol for two months, then isoniazid and rifampicin alone for a further four months...
The treatment of TB meningitis is isoniazid
Isoniazid
Isoniazid , also known as isonicotinylhydrazine , is an organic compound that is the first-line antituberculosis medication in prevention and treatment. It was first discovered in 1912, and later in 1951 it was found to be effective against tuberculosis by inhibiting its mycolic acid...
, rifampicin
Rifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...
, pyrazinamide
Pyrazinamide
Pyrazinamide is a drug used to treat tuberculosis. The drug is largely bacteriostatic, but can be bacteriocidal on actively replicating tuberculosis bacteria.-Abbreviations:...
and ethambutol
Ethambutol
Ethambutol is a bacteriostatic antimycobacterial drug prescribed to treat tuberculosis. It is usually given in combination with other tuberculosis drugs, such as isoniazid, rifampicin and pyrazinamide....
for two months, followed by isoniazid and rifampicin alone for a further ten months. Steroids are always used in the first six weeks of treatment (and sometimes for longer). A few patients may require immunomodulator
Immunomodulator
An immunomodulator, also known as an immunotherapy is a substance which has an effect on the immune system.- Immunosuppressants :Inhibits immune response in organ transplantation and autoimmune diseases.- Immunostimulants :...
y agents such as thalidomide
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
.
Treatment must be started as soon as there is a reasonable suspicion of the diagnosis. Treatment must not be delayed while waiting for confirmation of the diagnosis.
Hydrocephalus
Hydrocephalus
Hydrocephalus , also known as "water in the brain," is a medical condition in which there is an abnormal accumulation of cerebrospinal fluid in the ventricles, or cavities, of the brain. This may cause increased intracranial pressure inside the skull and progressive enlargement of the head,...
occurs as a complication in about a third of patients with TB meningitis and will require a ventricular shunt. The addition of aspirin may improve mortality, possibly by reducing complications such as infarcts.