Neurotuberculosis: an update

Abstract

Tuberculous (TB) meningitis (TBM), accounting for 70-80% of cases of neurotuberculosis, is one of the most severe forms of extrapulmonary tuberculosis. Two-thirds of new TB cases come from eight countries. Polymorphisms in toll-interleukin-1 receptor domain and in leukotriene A4 hydrolase (LTA4H) gene, affect the risk of inflammation in TBM. The common site of tuberculoma in children is cerebellum, and they may rarely develop tuberculous encephalopathy which has a high mortality. Young females with a high cerebrospinal fluid (CSF) protein have an increased predisposition to develop optochiasmatic arachnoiditis. Spinal TB meningitis may mimic transverse myelitis or Guillain-Barre syndrome. An extra-neural focus of TB should be sought clinically and radiologically as it may indicate safer and more accessible sites for diagnostic samplings. Cartridge-based nucleic acid amplification test (CBNAAT), also known as Genexpert test, is a polymerase chain reaction (PCR)-based method for detection of TB which also detects rifampicin resistance as it targets the rpob gene of mycobacteria. Line probe assays, based on PCR and reverse hybridization methods, identify mutations associated with drug resistance within a week. TBM being a paucibacillary disease, often evades a definite diagnosis and empirical treatment for a minimum of 9 months is warranted based on clinical judgement. All TBM patients should receive adjunctive corticosteroids, even those with HIV infection. Drug resistance is strongly associated with previous treatment and bedaquiline as well as delamanid have received approvals for multidrug resistant (MDR) TB. The key principle of managing MDR TB is never to add a single drug to a failing regimen. Correct combination and duration of most effective second line drugs in MDR TB require further modifications. Early shunting should be considered in those with hydrocephalus failing medical management. The single most important determinant of outcome is the stage of TBM at which treatment has been started.

Keywords: Bedaquiline; Chronic meningitis; Delamanid; Drug resistance; Paradoxical reaction; Rifampicin.