The clinical presentation of tuberculous meningitis is similar to other forms of chronic meningitis, which can make the diagnosis difficult to make and the differential broad. The clinical presentation is associated with fever, headache, altered sensorium, and focal neurologic deficits.  Typical neurologic deficits include facial palsy.[5] The additional diagnostic difficulty is that the symptoms can be present anywhere from a few days and up to six months. The clinical presentation of TBM is similar regardless of HIV status.[4]

Tuberculous meningitis assessment is by obtaining cerebrospinal fluid (CSF) for analysis. Typically, the CSF reveals low glucose, elevated protein, and modestly elevated WBC count with a lymphocytic predominance. The CSF analysis most closely resembles the CSF analysis of viral meningitis.[6]

Confirming the diagnosis of TB is a difficult diagnostic dilemma; this is especially true in resource-poor areas. Definitive diagnosis results from positive identification of MTB in the CSF. Standard Ziehl-Neelsen acid-fast bacilli (AFB) identification smears from CSF are highly unreliable. The positive yield of the AFB smear is broad with results ranging from 0% to 87%.[5] CSF mycobacterium cultures are variable in their yield and are only positive 40 to 83% of the time and can take from 6 to 8 weeks to grow.[6]   Daily large volume spinal taps, over a series of several days, sent for microbiological analysis can improve the culture sensitivity greater than 85%.[7] 

Various new sophisticated modalities for testing for antigens and antibodies specific for TB exist using PCR, but they have not won wide acceptance or utilization; this is due to a lack of access to the testing and high variability in the specificity of the results of the tests.  The choice of diagnostic in most cases is going to depend on the resources available. Despite advances in the development of improved and accurate diagnostic modalities MTB, confirmation by culture in the CSF remains the gold standard globally.[5][6][7] Culture allows for assessment of drug sensitivity results. Drug-resistant MTB carries up to twice the mortality.[7]

These diagnostic difficulties lead to decreased recognition of tuberculous meningitis and have led to the development of clinical algorithms to aid in the diagnosis of TBM and differentiation from other forms of meningitis.  The diagnostic algorithm bases its results on CSF values and patient clinical presentation. The criteria consist of the duration of symptoms greater than or equal to 5 days, neurologic impairment, CSF to serum blood glucose level ratio less than 0.5 and CSF protein level greater than 100 mg/dl. These algorithms have been tested in several trials; however, these have been retrospective trials and have not received validation through prospective trials. Therefore, high clinical suspicion must remain based on patient risk factors to diagnose TBM.[8][9]

Neuroimaging can further aid in the diagnosis of TBM. Magnetic resonance imaging (MRI) has demonstrated superiority to computed tomography (CT), as it is higher quality for assessment of the brainstem and spine in the detection of TBM. Imaging can assess cerebral infarcts, cerebral edema, and meningeal enhancement. CT imaging is best used to rule out the emergent complication of TBM related hydrocephalus that could result in the need for immediate neurosurgical intervention.  CT imaging can also show basal exudates.[7]

It is imperative that anti-tuberculous treatment starts in a timely fashion to reduce morbidity and mortality in tuberculous meningitis. First-line anti-tuberculous treatments have excellent CSF penetration. Treatment for TBM consists of two months of daily isoniazid (INH), rifampin (RIF), pyrazinamide (PZD) and either streptomycin (SM) or ethambutol (EMB). This regimen is then followed by 7 to 10 months of INH and RIF. This treatment plan is based on the assumption that the MTB is not a resistant strain. Drug sensitivities, however, can take months to result, at which time, treatment can be tailored to the identification of the drug sensitivities.[7]

Adjunctive therapy with corticosteroids has been used in the treatment of TBM. The goal of steroid treatment is to dampen the over-exaggerated response of the immune system which causes most of the neurologic complications seen with TBM including tissue damage and brain edema. There has been concern that steroids would reduce the penetration in the CSF of the anti-tuberculous medication but to date studies that have not shown this to occur. Studies have demonstrated improved clinical outcomes and reduced mortality with the administration of steroids. While there are no trials comparing which steroid is superior, mainstay treatment has been daily intravenous dexamethasone for up to four weeks followed by a four-week oral taper.[7] 

• Bacterial meningitis

• Viral meningitis

• Encephalitis of all causes

• Intracranial space-occupying lesions of various etiologies including infectious and non-infectious

• Non-specific viral syndromes

• Sepsis

• Acute cerebral vascular accident (CVA)

• A sympathomimetic syndrome due to drug abuse

• Delirium associated with urinary tract infection

Tuberculous meningitis is considered the deadliest form of MTB infection.[3] TBM carries a mortality rate between 20 and 67% with anti-tuberculous treatment and is fatal without treatment.[6] Patients at both ends of extremes of age and patients with HIV co-infection carry the highest mortality.[3][10] Prognosis of TBM depends on the patients’ neurologic status at the time of initial presentation and timeliness of the initiation of anti-tuberculous agents.[5] Patient who develop hydrocephalus secondary to MTB also has a poor prognosis even with neurosurgical intervention.[7][10]  

Tuberculous meningitis can cause a myriad of neurologic sequela that can be present at the time from the initial presentation and can produce residual effects even after successful treatment.[2]

Some significant complications to remember include:

• Hydrocephalus due to obstruction of CSF outflow causing raised intracranial pressure
• Hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion, this is seen in 40 to 50% of patients with TBM
• Tuberculomas can occur independently of TBM and have not been shown to be affected by adjunctive steroid treatment
• Vasculitis and stroke occur in 15 to 57% of patient with TBM depending on which diagnostic modalities is used in diagnosis with MRI being superior in diagnosis than CT.  

The primary goal in TB treatment of all forms involves medication regimen adherence. The treatment of all varieties of TB is lengthy, and without strict adherence, resistance develops which creates a considerable public health risk.

MTB eradication is a top priority in global health. Health care professionals across all disciplines are vital to the continued progress of this global effort. Globally, eradication efforts have involved every aspect of society. Collaboration between frontline clinicians, infectious disease nurses, pharmacists, and all government health entities will greatly improve the outcomes in these efforts. Public and private sector contributions are imperative to the advancements in diagnostic modalities and treatments in MTB.[11]

Tuberculous meningitis is a serious condition that requires an interprofessional team that includes physicians, with an emphasis on an infectious disease specialist, specialty infection control nurses, and pharmacy. By working together and maintaining open communication, the patient can receive appropriate care in a timely fashion. [Level V]