CNS Tuberculosis

Excerpt

Mycobacterium tuberculosis is responsible for 5.9% of community-acquired central nervous system (CNS) infections worldwide. Neurological or CNS tuberculosis (CNS-TB) may take 1 of 3 clinicopathological forms:

1. Tubercular meningitis (TBM), affecting the CNS diffusely

2. CNS tuberculoma, the focal type

3. Spinal arachnoiditis, also called "tuberculous radiculomyelitis" (TBRM), involving only the spine

Of these forms, TBM predominates as it causes 70% to 80% of CNS-TB infections. TBM presents with subacute-to-chronic meningitis signs and symptoms, with disease severity commensurate with illness duration. Diagnosis is fraught with challenges and is often delayed due to the varied and nonspecific presentations. Besides the clinical clues, diagnostic indicators in cerebrospinal fluid (CSF) include mononuclear pleocytosis, low sugar values, and high protein concentrations. Identifying Mycobacterium tuberculosis (MTB) in CSF by staining, culture methods, and molecular analysis is confirmatory but may be challenging.

Advanced radiological imaging techniques are usually of great assistance in making presumptive diagnoses. Vasculitic infarcts, cranial nerve (CN) palsies, multiple neurological deficits, and hydrocephalus frequently complicate CNS-TB. A strong clinical suspicion is typically enough to start prompt antitubercular therapy. The 4-drug regimen of isoniazid, rifampin, pyrazinamide, and ethambutol with adjunctive corticosteroid reduces morbidity and mortality. However, CNS-TB diagnosis and management may be complicated by drug resistance, immune reconstitution inflammatory syndrome (IRIS), and HIV coinfection.

Treatment efficacy depends upon the timing. Multiple factors determine the prognosis, the most important being the TBM clinical stage at initial presentation. Untreated or unrecognized TBM may cause death within 5 to 8 weeks of disease onset.

Normal Protective Barriers of the Central Nervous System

The CNS is shielded from potentially harmful blood-borne bacteria by 2 vascular barriers: the blood-brain barrier (BBB) and blood-CSF barrier (BCSFB). The BBB, primarily consisting of brain microvascular endothelial cells, regulates the passage of substances between the blood and CNS with tight junctions and specialized transport mechanisms. Supporting elements like pericytes and astrocytes also play crucial roles in maintaining BBB integrity. In contrast, the BCSFB is formed by choroid plexus epithelial cells and the arachnoid membrane, similarly employing tight junctions to control the exchange between blood and CSF.

However, in vitro and animal models have shown that MTB can invade brain endothelial cells by rearranging cellular actin molecules. The MTB gene Rv0931c is implicated in promoting CNS infection by facilitating bacillary endothelial adhesion. MTB may also exploit the "Trojan horse" mechanism, utilizing infected macrophages and neutrophils to traverse the BBB.