What is CNS Tuberculosis?
Mycobacterium tuberculosis is responsible for nearly 6% of central nervous system (CNS) infections that people catch in the community around the world. This bacteria can cause a type of infection called CNS Tuberculosis (CNS-TB) in three different forms:
* Tubercular meningitis (TBM), which affects the CNS all over
* CNS tuberculoma, which is focused in one area
* Spinal arachnoiditis – also known as tuberculous radiculomyelitis (TBRM), which only involves the spine
Among these, TBM is the main form as it makes up 70% to 80% of CNS-TB infections. TBM often shows up with signs and symptoms of meningitis that slowly worsen over time. The disease severity matches the length of the illness. Diagnosing TBM is quite difficult and usually delayed because its symptoms can be varied and unclear. Besides the symptoms, doctors also look for indicators in the cerebrospinal fluid (CSF) which include high levels of certain cells, low sugar levels, and high protein levels. It can sometimes be challenging to find Mycobacterium tuberculosis in the CSF, but if found, it confirms the diagnosis.
Radiological imaging techniques are typically very helpful in suggesting a diagnosis of CNS-TB. CNS-TB complications often include strokes caused by inflammation in blood vessels, paralysis in cranial nerves, multiple neurological impairments, and a condition called hydrocephalus. Usually, the suspicion of CNS-TB is enough for doctors to start prompt antitubercular therapy. The standard treatment includes four drugs – isoniazid, rifampin, pyrazinamide, and ethambutol, alongside corticosteroids to reduce complications and risk of death. However, diagnosing and managing CNS-TB can be complicated due to drug resistance, immune reactions, and HIV co-infection.
The success of the treatment depends on when it starts. Several factors determine the disease’s prognosis, with the most crucial being the stage of TBM at the time of initial diagnosis. If TBM is left untreated or undiagnosed, it can cause death within 5 to 8 weeks of the disease starting.
The CNS is protected from harmful bacteria in the blood by two barriers: the blood-brain barrier (BBB) and blood-CSF barrier (BCSFB). The BBB prevents substances in the blood from entering the CNS, while BCSFB controls the exchange between blood and CSF. However, research has shown that Mycobacterium tuberculosis can invade brain cells, thus promoting CNS infections. The bacteria can also use infected immune cells to cross the BBB, a process akin to the “Trojan Horse” strategy.
What Causes CNS Tuberculosis?
The bacteria that causes CNS-TB, known as MTB, can be seen using special dyes under a microscope, such as Ziehl-Neelsen, auramine-rhodamine, and Kinyoun stains. It’s important to note that the contribution of the other 4 Mycobacterium species in causing CNS-TB isn’t confirmed. Also, humans are the only known hosts or places where MTB can live. In most cases, people get infected through tiny droplets in the air from those already carrying the bacteria.
Risk Factors and Frequency for CNS Tuberculosis
MTB, a type of bacterial infection, affects approximately 25% to 30% of the global population. CNS-TB, a specific type of this infection, is found in 1% to 2% of those with active tuberculosis. CNS-TB makes up about 5% to 8% of all cases of tuberculosis that doesn’t affect the lungs in people who have a healthy immune system. The majority, or 70% to 80%, of people with CNS-TB have a condition called TBM.
In places like India and other parts of Asia, a condition called tuberculomas is quite common. Tuberculomas account for about 20% to 30% of all conditions that take up space within the skull. As an example of the prevalence of CNS-TB, in 2016 in the United States, there were about 9,272 diagnosed cases.
Since 2010, the number of people getting tuberculosis has been decreasing by 2% to 3% every year. This trend was especially noticeable in 2020, possibly due to efforts to limit the spread of diseases, travel restrictions, or missed or delayed tuberculosis diagnoses during the pandemic. However, the number of reported cases of tuberculosis increased by 9.4% between 2020 and 2021.
Even though medical technology has improved to better diagnose and treat CNS-TB, it’s still a serious condition. It has a death rate of 15% to 40%, with children unfortunately being the most affected.
Signs and Symptoms of CNS Tuberculosis
TB, or tuberculosis, affecting the central nervous system can take different forms, which produce different symptoms. Below is a brief overview of each:
- Tuberculous Meningitis (TBM): Patients usually experience symptoms like feeling tired, fever, night sweats, and headaches. This can progress to more severe symptoms, such as vomiting, changes in personality and confusion. Seizures and difficulty in moving or sensing can also develop. Children might have increased irritability, vomiting, and seizures. Around 20% to 30% of TBM patients may experience issues with their cranial nerves, which can lead to conditions like blindness.
- Tuberculoma: This form often shows up in younger people as lesions in the brain. The symptoms include headaches, seizures, gradual neurological problems, and optic nerve swelling sometimes combined with meningitis.
- Spinal Arachnoiditis: People with this condition usually show symptoms of radiculomyelopathy, an issue affecting the spinal nerve roots and spinal cord. Symptoms include pain radiating along a nerve, heightened sense of touch, loss of muscle strength, and incontinence. There might also be issues with blood supply to the spinal cord, leading to infarction, or tissue death.
- Atypical Presentations: Sometimes, CNS-TB presents unusually in 10% to 30% of adult patients with widespread TB. These patients might have multiple small areas of inflammation throughout the brain. TBM can also present as gradual cognitive decline or mental health conditions in rare cases. Some people might also have multiple brain nerve issues or complications with fluid build-up in the brain.
- Tuberculous Meningitis and HIV Infection: Those with both HIV and TBM generally experience the same symptoms and have the same outlook as those with just TBM. However, they are more likely to have normal spinal fluid results, making imaging tests more crucial. They are also more likely to develop tuberculoma in the brain and should be aware that conditions that mimic TBM are often concurrent in HIV sufferers.
Testing for CNS Tuberculosis
Diagnosing Tuberculous Meningitis, a condition caused by a certain type of bacteria invading the central nervous system, can be quite challenging. Traditional methods used for diagnosis can be unreliable and take a long time. Doctors typically rely on a mix of patient history, neurological exams, cerebrospinal fluid (CSF) analysis, and brain imaging to make a diagnosis.
New molecular techniques can help to identify the bacteria in the cerebrospinal fluid, but a definite diagnosis is not always possible. This uncertainty often necessitates starting treatment without a confirmed diagnosis to avoid any risks associated with delaying treatment. It’s also important to explore factors like the patient’s history of tuberculosis exposure which can be identified in a significant number of children with Tuberculous Meningitis.
Looking for signs of active infection in areas outside the nervous system can occasionally help in diagnosis. In many child and adult cases, chest X-rays are useful. Similarly, blood tests might show mild anemia, increased white blood cells, and low sodium levels. A positive tuberculin test can add supporting evidence, especially in children, though a negative result does not rule out the disease. An eye exam might also reveal signs that can help with diagnosis.
When examining cerebrospinal fluid, certain features can be indicative of Tuberculous Meningitis. The fluid may contain a higher number of certain types of cells and high protein content. The sugar levels in the fluid may also be lower than normal.
Microscopic and molecular tests can be used to detect the bacteria in the CSF, but these tests are not always reliable. Some cutting-edge techniques like Xpert MTB/rifampin, a type of DNA test, have been recommended by the World Health Organization for confirming diagnoses in certain circumstances. Other promising tests include lipoarabinomannan detection and interferon-γ release assays. Adenosine deaminase (ADA), a specific enzyme whose levels increase in Tuberculous Meningitis, might be additionally helpful in diagnosis.
Brain imaging also plays a key role in making a timely and accurate diagnosis. Techniques include computed tomography (CT) or magnetic resonance imaging (MRI), with the latter often providing more detailed images. Some common findings in Tuberculous Meningitis include brain inflammation, fluid buildup inside the skull, and tissue damage in the form of strokes.
Lastly, signs of Tuberculous Meningitis may also be visible in the spinal cord, with techniques like phase-contrast MRI able to uncover signs such as swelling and altered signals in the cord.
Treatment Options for CNS Tuberculosis
Central Nervous System Tuberculosis – a highly deadly disease that is challenging to diagnose -may be treated with antituberculous therapy and corticosteroids on initial suspicion. Patients must be continuously monitored for drug reaction and disease complications. No universally accepted drug combination, dosage, or treatment duration is known, so doctors must consider the susceptibility to drugs and how the patient reacts to the treatment.
For drug-susceptible tuberculosis, four oral medications are generally used in the first two months: isoniazid, rifampicin, pyrazinamide, and ethambutol. Then, pyrazinamide and ethambutol may be discontinued, extending the regimen for at least seven months. If pyrazinamide is not used in the initial phase, treatment may be stretched to 18 months.
The treatment for drug-resistant tuberculosis is similar but more complicated due to overlapping drug reaction profiles. Treating tuberculomas, or growths caused by tuberculosis, involves using standard antituberculous therapy for 9-12 months, with over 80% of patients experiencing clinical and physical improvement by nine months. If more traditional methods fail, surgery may be employed.
For viral tuberculosis, therapy is recommended for 6-9 months or even up to 24 months, depending on the patient’s response, with surgery considered in severe cases.
The use of complementary steroid therapy remains a topic of ongoing debate due to mixed data on its effectiveness. However, prescriptions such as dexamethasone have been shown to improve survival rates when used alongside standard treatment. Other anti-inflammatory drugs, like Thalidomide and Infliximab, have also been used with some success.
Monitoring for worsening symptoms is key for patients undertaking treatment as Clinical or radiological deterioration may occur even when treatment initially seems to be working.
HIV-positive patients naïve to antiretroviral therapy should begin their therapy 8 to 10 weeks after starting antituberculous therapy to reduce the risk of early tuberculosis-associated complications.
If the disease causes hydrocephalus, or fluid accumulation in the brain, it can be initially managed with corticosteroids, diuretics, and temporary external ventricular drainage. If standard treatment efforts are ineffective, surgery may be considered.
To summarize, the treatment of Central Nervous System Tuberculosis is contingent on the patient’s susceptibility to drugs, the type of tuberculosis (drug-susceptible or resistant), the presence of other diseases (e.g., HIV), and the overall progression of the disease.
What else can CNS Tuberculosis be?
Diagnosing Tuberculosis Meningitis (TBM) can be tough because there are many conditions that can look very similar. It is crucial for doctors to rule out other diseases that can cause chronic meningitis or meningoencephalitis, especially in people with weakened immune systems. These conditions can include:
- Fungal meningitis (especially cryptococcal meningitis)
- Neurobrucellosis
- Neurosyphilis
- Neuroborreliosis
- Neurosarcoidosis
- Treated bacterial meningitis
- Neoplastic meningitis
- Systemic inflammation affecting the Central Nervous System (CNS)
Brain scans and neuropathology can be key tools for doctors as they navigate these challenging diagnoses.
A Tuberculoma, another form of brain tuberculosis, can look very similar to several other conditions:
- Neurocysticercosis
- Cryptococcoma
- Central Nervous System (CNS) lymphoma
- Primary or metastatic brain tumors
Some types of brain infections and inflammations, like herpes simplex and parameningeal infections (like brain abscesses), can also resemble a Tuberculoma. CNS toxoplasmosis, a parasitic infection, is another important possibility to rule out, particularly in those with HIV.
In diagnosing spinal arachnoiditis, a condition caused by inflammation of the protective membranes around the brain and spinal cord, doctors need to distinguish it from other spinal diseases:
- Intradural spinal tuberculoma
- Extradural compressive myelopathy related to tuberculous spondylitis, a form of spinal tuberculosis
- Noncompressive acute transverse myelitis
- Guillain-Barre syndrome
Cytomegalovirus polyradiculopathy, an illness that affects the nerves, can also confuse diagnoses, especially in people with HIV.
What to expect with CNS Tuberculosis
The outlook for Central Nervous System Tuberculosis (CNS-TB) remains grim even with treatment. The mortality rate for Tuberculous Meningitis (TBM), a form of CNS-TB, varies between 9.8% and 57%. This condition is known to cause significant neurological issues, particularly affecting children.
Numerous factors can predict the mortality rate and neurological complications. These factors include age, length of symptom occurrence, Glasgow Coma Scale score (which measures a person’s consciousness level), absence of headaches, the protein level in the Cerebrospinal Fluid (CSF), the severity of arachnoiditis (a type of brain inflammation), presence of complications, and severity stage as determined by the Medical Research Council.
Possible Complications When Diagnosed with CNS Tuberculosis
Tuberculosis of the central nervous system (CNS-TB) can be fatal or cause severe complications. Early complications can emerge from an inflammation of the membranes covering the brain and spinal cord, leading to issues such as fluid build-up in the brain, loss of vision related to ocular complications, specific neurological problems, stroke, partial paralysis from inflammation of the arteries, brain swelling, seizures induced by the formation of nodules or abscess in the brain, and disorders related to the production and secretion of antidiuretic hormone. Inflammation of the spinal cord is seen in 10% of cases of TBM and can pave the way to adverse outcomes. It’s noteworthy that about 10-30% of people with TBM end up with long-lasting neurological problems, including the aforementioned complications, in addition to learning disabilities, dementia, hormonal disorders, and walking disturbances.
Complications of CNS-TB:
- Fluid build-up in the brain
- Loss of vision related to ocular complications
- Specific neurological problems
- Stroke
- Partial paralysis from inflammation of the arteries
- Brain swelling
- Seizures induced by the formation of nodules or abscess in the brain
- Disorders related to the production and secretion of antidiuretic hormone
- Inflammation of the spinal cord
- Learning disabilities
- Dementia
- Hormonal disorders
- Walking disturbances
Recovery from CNS Tuberculosis
Treatment for TBM requires intensive rehabilitation and careful medical treatment to decrease disability and promote healing. The rehabilitation process should start during the hospital stay or while in intensive care, and continue at home after discharge. The rehabilitation should include various sensory stimulation techniques to help the brain recover, along with specific postures and positioning to prevent problems related to being immobilized.
Such treatment also includes both passive and active exercises to maintain muscle strength and specific therapy for the chest to reduce the risk of pneumonia and aspirating, or breathing in foreign substances. Long-term rehabilitation is crucial for patients who continue to have neurological issues.
Preventing CNS Tuberculosis
patients and their caregivers need to understand the importance of taking medications consistently, especially since Tuberculosis in the central nervous system (CNS-TB) requires long-term treatment. They also need to be aware of the possible complications that can arise from both the disease and its treatment. It’s essential for patients and their family members to make regular hospital trips, undergo necessary medical tests, and follow up closely with their doctor. This helps to make sure that the disease is improving and also helps to prevent any bad reactions to the medication.
