What is the diagnosis and treatment for a patient with paraparesis, multiple brain infarcts on MRI, multiple FDG-positive lymph nodes in the mesenteric region on PET, and a biopsy showing intracellular Acid-Fast Bacilli (AFB), suggesting possible CNS involvement and immunocompromised status, potentially with HIV and a low CD4 count?

CNS Tuberculosis with Disseminated Disease in an Immunocompromised Patient

This patient has disseminated tuberculosis with CNS involvement (tuberculous meningitis and/or tuberculomas) causing multiple brain infarcts and paraparesis, requiring immediate empirical anti-tuberculosis therapy without waiting for culture confirmation. 1

Immediate Management

Start empirical four-drug anti-tuberculosis therapy immediately - the combination of paraparesis, multiple brain infarcts, intracellular AFB on biopsy, and FDG-positive mesenteric lymph nodes strongly suggests disseminated TB with CNS involvement, which is a medical emergency where treatment delay is strongly associated with death. 1

Standard Anti-TB Regimen

• Intensive phase (2 months): Isoniazid 5 mg/kg (up to 300 mg daily), rifampin, pyrazinamide, and ethambutol 15 mg/kg as single daily doses 2, 3, 1
• Continuation phase (minimum 10 months): Isoniazid and rifampin for at least 10 additional months - CNS tuberculosis requires prolonged therapy beyond the standard 6-month pulmonary TB regimen 1

Critical Adjunctive Therapy

Administer corticosteroids (dexamethasone or prednisolone) to all patients with CNS tuberculosis regardless of disease severity - this reduces mortality and improves neurological outcomes in tuberculous meningitis. 1

Diagnostic Workup

Essential CSF Analysis

• Perform lumbar puncture immediately (unless contraindicated by mass effect) to examine CSF for: lymphocytic pleocytosis, elevated protein, and CSF:plasma glucose ratio <50% - these findings support TBM diagnosis 4, 1
• Submit large CSF volumes (≥5 mL) for AFB smear and culture - sensitivity of culture for tuberculous meningitis ranges from 25-70%, with highest yields from larger volumes 4
• Request CSF PCR for M. tuberculosis - though sensitivity in non-respiratory specimens may be poor, it can provide rapid confirmation when positive 4

HIV Testing and CD4 Count

Test for HIV infection immediately - the combination of disseminated TB, CNS involvement, and multiple brain infarcts suggests severe immunocompromise, likely HIV with low CD4 count. 4

• If HIV-positive with CD4 <200 cells/μL, initiate prophylaxis against Pneumocystis jirovecii pneumonia 5
• Screen for other opportunistic infections including CMV, toxoplasmosis, and cryptococcosis 4

Neuroimaging

MRI brain is essential to characterize the extent of CNS involvement - tuberculomas appear as ring-enhancing lesions, while tuberculous meningitis shows basilar meningeal enhancement and may cause vasculitis leading to infarcts. 1, 6

Special Considerations for HIV Co-infection

Antiretroviral Therapy Timing

If HIV-positive, initiate ART during TB treatment to ensure sustained viral suppression and immune reconstitution, but coordinate timing carefully with infectious disease specialists to manage drug interactions and immune reconstitution inflammatory syndrome (IRIS) risk. 5, 4

Drug Interactions

Avoid enzyme-inducing anticonvulsants (phenytoin, carbamazepine) if seizures occur, as they affect metabolism of both anti-TB drugs and antiretrovirals - use levetiracetam or valproate instead. 7, 2

Monitor for rifampin-ART interactions - rifampin induces cytochrome P450 enzymes and may reduce levels of protease inhibitors and some integrase inhibitors, requiring ART regimen adjustment. 4, 5

Monitoring During Treatment

Hepatotoxicity Surveillance

Obtain baseline transaminases and monitor monthly - patients with HIV co-infection, daily alcohol use, or age >35 have higher risk of isoniazid-associated hepatitis. 2

• Temporarily discontinue isoniazid if transaminases exceed 3-5 times upper limit of normal 2
• Daily alcohol users have particularly high risk and require closer monitoring 2

Neurological Monitoring

Monitor for visual changes monthly during the initial 60-day period when ethambutol dose is 25 mg/kg - ethambutol can cause optic neuritis, particularly at higher doses. 3

Assess for peripheral neuropathy - isoniazid depletes pyridoxine and can cause neuropathy, particularly in HIV-positive patients; consider pyridoxine supplementation. 2

Differential Diagnosis Considerations

Distinguishing from Primary CNS Lymphoma

The FDG-PET findings create diagnostic complexity - primary CNS lymphoma shows high FDG uptake while toxoplasmosis typically shows low uptake, but TB can show variable uptake patterns. 8, 9

• The presence of intracellular AFB on biopsy confirms mycobacterial infection 6, 10
• If AFB culture remains negative but clinical suspicion remains high, consider repeat biopsy or empirical treatment continuation 6

Other Opportunistic Infections

In HIV-positive patients with CD4 <200, the differential includes: 4

• Toxoplasmosis (most common, but biopsy showed AFB not tachyzoites)
• Cryptococcal meningitis (perform CSF cryptococcal antigen testing)
• Progressive multifocal leukoencephalopathy (JC virus PCR)
• CMV encephalitis (CSF CMV PCR)

Critical Pitfalls to Avoid

Never delay anti-TB therapy while awaiting culture confirmation - M. tuberculosis culture can take 6-8 weeks, and treatment delay in CNS TB is strongly associated with mortality and permanent neurological disability. 1

Do not use isoniazid alone or in two-drug regimens initially - this promotes resistance development; always use four-drug therapy in the intensive phase. 2

Avoid premature treatment discontinuation - CNS tuberculosis requires minimum 12 months total therapy (2 months intensive + 10 months continuation), not the standard 6-month pulmonary TB regimen. 1

Monitor for immune reconstitution inflammatory syndrome (IRIS) if initiating ART in HIV-positive patients - paradoxical worsening of TB manifestations can occur 2-8 weeks after ART initiation, potentially requiring increased corticosteroid doses. 4