Across the world, TB is still a serious public health issue that primarily affects underdeveloped nations [8]. Moreover, due in part to co-infection with HIV, its prevalence has increased in wealthy countries. According to the 2019 WHO report, there were 10 million new cases and 1.5 million fatalities [9]. TB typically affects the lungs or other organs on occasion (extrapulmonary). Tuberculous meningitis localization is rare. A significant obstacle to national, regional, and international TB control strategies is drug-resistant TB. Fluoroquinolones and aminoglycosides are two second-line antibacterials against which some MDR pathogens have established additional resistance mechanisms. Around 200,000 fatalities and 500,000 new cases of MDR-TB or rifampicin-resistant TB (RR-TB) are reported each year globally [10].

Tuberculous meningitis is a subacute meningeal condition, which presents itself in different stages: The first stage is characterized by nonspecific symptoms: subfebrileness, headache, irritability, drowsiness, malaise, vomiting, photophobia, apathy and low weight/weight loss. In infants, it can be present symptoms: stagnation/loss of landmarks in development, fever, cough, altered consciousness, and convulsions. Neck stiffness is characteristically absent. It lasts about 1-2 weeks. The presence of signs and symptoms nonspecific makes it difficult to suspect and diagnose TBM in the first stage. A history of contact with a patient with an active form of tuberculosis (~ 50% cases) can be also important.

The second stage is usually characterized by an onset suddenly, with the following signs: lethargy, stiffness of the neck, positive meningeal signs, hypertonia, convulsions, vomiting, and focal neurological deficit. Along the way, the development of hydrocephalus occurs, the increase in intracranial pressure, encephalitis with orientation/movement/ movement disorders speech, involvement of the cranial nerves (30% -50% cases), the most common - the VI-th nerve, and loss of vision. Next comes the third stage, in which the association takes place posture of decortication/decerebration, hemiplegia, coma, and possibly death [11].

Seizures are a rare symptom of TBM in adults, and their presence should encourage the doctor to rule out other conditions including cerebral tuberculoma or bacterial or viral meningitis. In contrast, seizures are a common symptom of TBM in children, occurring in up to 50% of pediatric cases. When allowed to progress without treatment, coma, and death almost always ensue. In survivors of TBM, neurologic sequelae may occur that include mental retardation in children, sensorineural hearing loss, hydrocephalus, cranial nerve palsies, stroke-associated lateralizing neurological deficits, seizures, and coma [12].

TBM diagnosis can be challenging, and it can not even be supported by conclusive microbiologic confirmation but simply by clinical and early cerebrospinal fluid (CSF) findings. The likelihood of TBM is increased by several clinical traits, including greater symptom duration (>six days), significant CSF pleocytosis, and the presence of localized impairments. The following are typical CSF findings of TBM: lymphocytic-predominant pleocytosis. Total white cell counts are usually between 100 and 500 cells/μL. Very early in the disease, lower counts and neutrophil predominance may be present, elevated protein levels, typically between 100 and 500 mg/dL, low glucose, usually less than 45 mg/dL, or CSF: plasma ratio <0.5 [5].

With the crucial caveat that a single sample has limited sensitivity, in the range of 20%-40%, a CSF sample should be sent for an acid-fast smear. For a microbiologic diagnosis, several daily large volumes (10-15 mL) of lumbar punctures are frequently required; four spinal taps raise sensitivity to >85% [13-14]. Even though culture has a low sensitivity (40-80%) and can take many weeks, it should be used to assess medication susceptibility. Important prognostic and therapeutic ramifications of drug-resistance strains include TBM caused by isoniazid- (INH-) resistant M. tuberculosis strains.

It is important to stress that a negative CSF test for M. tuberculosis DNA or acid-fast bacilli does not rule out the diagnosis of TBM or eliminate the need for empiric therapy if the clinical suspicion is high. Mycobacterial DNA may be detectable in the CSF for up to a month after treatment begins, although the sensitivity of CSF smear and culture rapidly declines following treatment [5].

Through numerous research, molecular biology has proven to be successful even on paucibacillary samples by enabling the identification and detection of anti-TB medication resistance. The World Health Organization (WHO) recommends the quick, automated GeneXpert MTB/RIF nucleic acid amplification test for the simultaneous identification of MTC and rifampicin resistance in pulmonary and extrapulmonary specimens. In cerebral spine fluid, it is more than 80% sensitive [15] In our case, GeneXpert MTB/RIF allowed the identification of MTC and detection of rifampicin resistance.

Neuroimaging can be useful in the diagnosis of TBM. Basal meningeal enlargement and hydrocephalus are typical TBM neuroradiologic characteristics [5]. There may also be nodular-enhancing lesions, cerebral edema, and hypodensities brought on by cerebral infarcts. The imaging test of choice for identifying TBM-related anomalies is magnetic resonance imaging (MRI), which is superior to computed tomography (CT) for assessing the brainstem and spine. Nonetheless, CT is sufficient for a quick assessment of hydrocephalus associated with TBM for potential surgical intervention.

The MTB-DR plus and MTB-DRsl genotyping assays, in addition to the GeneXpert MTB/RIF, enable the diagnosis of MTC from lung clinical specimens or cultured samples. Rifampicin and isoniazid resistance are detected using the MTBDRplus test [7]. The MTB-DRsl test is made to look for ethambutol resistance on the embB gene, fluoroquinolone resistance on the rrs gene, and aminoglycoside resistance on the gyrA gene. For the identification of resistance to rifampicin, isoniazid, fluoroquinolones, and aminoglycosides, the MTBDRplus test and the MTBDRsl test have a sensitivity higher than 80% [16].

In our case, the CSF was positive by GeneXpert MTB/RIF with the detection of rifampicin resistance. The MTBDRplus test confirmed resistance to rifampicin and isoniazid and the MTBDRsl test showed additional resistance to Hydrazide, Ethionamide, Quinolone, Amikacin, Kanamycin, and Capreomycin.

Primary drug resistance is defined as resistance in a patient who has never received TB treatment. Antibacillary medication resistance can also be secondary. Mycobacterium tuberculosis treatment places selection pressure on the population, which causes a decline in susceptible bacilli, a rise in drug-resistant mutations, and the formation of drug resistance (acquired resistance).  It seems safe to assume that our patient has acquired primary drug resistance by being in contact with her brother-in-law.

The WHO recommends a brief regimen of 9-11 months for treating MDR-TB in all of its variants, which comprises a 4-6 month loading phase with high doses of amikacin, moxifloxacin, ethionamide, clofazimine, pyrazinamide, ethambutol, and isoniazid. Patients are given moxifloxacin, clofazimine, pyrazinamide, and ethambutol during the maintenance phase. 2020 saw an update to the WHO's recommendations that short regimens without injectables be replaced with shorter regimens that incorporate bedaquiline. If the three drugs have never been combined before, 2019 WHO trial that the FDA approved suggests bedaquiline, linezolid, and pretomanide for 9 months to treat multiresistant tuberculosis or XDR-TB [16].

Pyrazinamide has excellent penetration into the CSF and is a key drug in reducing the total treatment time for drug-susceptible TB. Given that the newer generation fluoroquinolones, such as levofloxacin, and moxifloxacin, have excellent CSF penetration and safety profiles as well as strong effectiveness against the majority of M. tuberculosis strains, FQN would seem to have considerable potential as part of the first-line therapy for TBM. The addition of an FQN to the usual regimen improved anti-TB performance as determined by several clinical parameters in a randomized controlled study for the treatment of TBM. Although there was no significant difference in mortality, the study's power was probably insufficient to show such a relationship. Among new anti-TB agents, bedaquiline (TMC207, a diarylquinoline) and demand (OPC-67683, a nitro-dihydroimidazo-oxazole) appear to be the most promising drugs [17].

It is advised to assess therapy tolerance as well as conduct clinical, bacteriological, and radiological surveillance. The use of new anti-TB medications like linezolid and bedaquiline has helped the prognosis of MDR pulmonary and extrapulmonary TB. The availability of still-active molecules affects the treatment's effectiveness. Those with XDR-TB and HIV infection have had high mortality, nevertheless. The rise of MDR and XDR strains as well as their synergistic connection with TB may help to explain this [15].

Prognosis is influenced by the neurologic state at the time of presentation and the length of time until treatment begins heavily influences the prognosis for TBM. When the diagnosis of TBM is suspected, empiric treatment should start right once because any delay in treatment can exacerbate the prognosis, even though the course of TBM is typically not as fast or fulminant as meningitis caused by pyogenic bacteria. According to several case studies, the death rate ranges from 7% to 65% in industrialized nations and from up to 69% in impoverished regions [18-19]. Comorbidities, substantial neurologic involvement at admission, rapid disease progression, and advanced or very young age all increase the chance of death. Up to 50% of survivors experience neurologic aftereffects [20].