A 67-year-old male presented with a two-week history of recurrent fever and one week of mental dullness and generalized limb weakness culminating in inability to walk. Fever peaked at 39.3 °C and prior treatment with ceftriaxone produced no improvement. On admission the patient was apathetic, slow to respond, with impaired recent memory and calculation but preserved orientation and judgment. Muscle strength was 3/5 in all limbs. Neck stiffness was present; Kernig and Brudzinski signs were negative. Initial management included osmotic dehydration with mannitol for raised intracranial pressure.
Lumbar puncture on hospital day two documented an elevated opening pressure (250 mmH2O). CSF analysis revealed marked inflammatory changes: nucleated cells 310 × 10^6/L with lymphocytic predominance, protein 2.19 g/L, glucose 2.2 mmol/L, and chloride 96.4 mmol/L. Microbiologic testing demonstrated a positive CSF GeneXpert MTB/RIF assay for Mycobacterium tuberculosis, whereas CSF acid-fast staining and CSF metagenomic next-generation sequencing (mNGS) were negative. Serum T-SPOT.TB was borderline. Autoimmune testing by cell-based indirect immunofluorescence showed GFAP antibodies positive in serum (1:100) and CSF (1:10). Antibodies to AQP4, MOG, and MBP were negative. Tumor markers were largely normal apart from mildly elevated total PSA. Serum sodium was low (129.4 mmol/L).
Brain MRI at presentation showed multiple abnormal cortical and subcortical T2/FLAIR hyperintense lesions involving the right frontal, insular, and occipital regions, abnormal sulcal hyperintensity in the right hemisphere, and multiple linear and punctate leptomeningeal contrast enhancements. Chest CT identified partial consolidation in both lower lobes and subpleural fibrotic changes at the apices.
Based on the clinical syndrome of meningitis and encephalopathy, a positive CSF GeneXpert result, CSF inflammatory profile, and positive GFAP antibodies in CSF and serum, clinicians diagnosed concurrent tuberculous meningoencephalitis and GFAP astrocytopathy. Antituberculous therapy initiated included isoniazid, rifampicin, ethambutol, pyrazinamide, and moxifloxacin. Immunotherapy began with intravenous methylprednisolone (250 mg/day for 5 days, then 125 mg/day for 3 days) followed by oral prednisone 60 mg/day.
The patient demonstrated clinical improvement within 10 days: normalized temperature, resolution of meningeal signs, better responsiveness, and improved limb strength enabling assisted ambulation. After one month of combined treatment muscle strength returned to normal, but cognitive deficits persisted (MMSE 23, MoCA 18). Prednisone was discontinued at one month. Repeat MRI performed at that time showed increased T2/FLAIR hyperintensity and newly developed nodular and more prominent leptomeningeal enhancement despite ongoing antituberculous therapy. Prednisone 60 mg/day was reintroduced for four weeks and then tapered by 10 mg every two weeks.
At three-month follow-up, fever and limb weakness had not recurred, though memory and calculation deficits remained. Repeat lumbar puncture showed improvement: opening pressure fell to 100 mmH2O, CSF WBC declined to 130 × 10^6/L, protein decreased to 1.56 g/L, and glucose and chloride increased. GFAP antibodies in both serum and CSF converted to negative. Follow-up brain MRI showed marked regression of previously enhanced lesions after steroid reintroduction and tapering.
This case illustrates the substantial clinical, CSF, and imaging overlap between tuberculous meningoencephalitis and GFAP astrocytopathy, which can complicate diagnosis. Tuberculous meningoencephalitis often yields low direct-pathogen detection rates in CSF; GeneXpert provided positive evidence here while acid-fast staining and mNGS were negative. GFAP astrocytopathy can present with fever, meningitic features, hyponatremia, and leptomeningeal or perivascular enhancement on MRI, contributing to misdiagnosis risk. The presence of GFAP antibodies in CSF and serum and steroid responsiveness supported a coexisting autoimmune process in this patient.
Radiological deterioration after steroid withdrawal raised two principal considerations: a paradoxical reaction related to effective antituberculous therapy, or relapse/persistence of autoimmune inflammation due to inadequate immunosuppression. Paradoxical worsening in tuberculous central nervous system disease is recognized within the first three months of therapy and is attributed to exaggerated host inflammatory responses to mycobacterial antigens released during treatment. GFAP astrocytopathy is also prone to relapse during steroid tapering. In this case, reintroduction of glucocorticoids produced radiologic and laboratory improvement and seroconversion to GFAP antibody negativity, favoring an autoimmune component responsive to immunomodulation.
Pathogenically, infection-triggered exposure of intracellular antigens and subsequent T cell–mediated responses have been proposed as potential links between CNS infection and autoimmune GFAP-targeted disease. The report acknowledges these mechanisms remain speculative; a coincidental coexistence cannot be excluded.
Management implications include the need for combined anti-infective and immunomodulatory therapy when both processes are suspected, close monitoring for paradoxical reactions or autoimmune relapse, and careful planning of steroid tapering to minimize clinical and radiologic deterioration.
Concurrent tuberculous meningoencephalitis and GFAP astrocytopathy represent a rare overlap syndrome with overlapping clinical, cerebrospinal fluid, and imaging features. Diagnosis relies on integrated clinical, microbiological, and antibody testing. These cases may experience paradoxical or autoimmune-related worsening during steroid tapering, and optimal care requires coordinated anti-tuberculous treatment with thoughtfully timed immunosuppression and close follow-up.