A 23 year-old black male with past medical history of chronic cough presented for a witnessed, new-onset seizure. He was initially brought to an outside emergency department where a head CT showed possible septic emboli to the brain, then transferred to our institution for higher level of care. He reported diaphoresis, muscle aches, and a 20-lb weight loss over the last three months. Other than the above, review of systems was negative for confusion, headache, vision changes, slurred speech, focal weakness, numbness, urinary incontinence, bowel incontinence, rashes, or arthralgias.
Upon further history, the patient had undergone a recent workup for chronic cough and fevers one month ago. He was found to have right-sided hilar and mediastinal adenopathy by chest CT and underwent bronchoscopy. Bronchoalveolar lavage at the time was negative for TB, but positive for Streptococcus viridans and methicillin-susceptible Staphylococcus aureus. Multiple transbronchial biopsies were negative for malignancy or granulomas. He also had negative serologies for human immunodeficiency virus (HIV), cytomegalovirus (CMV), Bartonella, and syphilis, and was discharged with a course of antimicrobials for presumed bacterial pneumonia. Travel history was significant for a visit to Key Largo, Florida eight months ago. The patient was a college student and denied alcohol, tobacco, recreational drug use, or exposure to recent sick contacts.
Vitals on admission were significant for elevated heart rate of 98 beats per minute. Physical exam revealed a tongue laceration and decreased right-sided breath sounds, but no neurological abnormalities. Labs were notable for microcytic anemia with low percent iron saturation, ESR 78 mm/hr, and CRP 5.59 mg/dL. Immunoglobulin (IgG, IgM, IgA) levels showed no evidence of humoral immunodeficiency. QuantiFERON-TB Gold was positive. CT chest showed predominantly right-sided pleural effusion and mediastinal lymphadenopathy (Fig. 1). Brain MRI with and without contrast showed multiple, peripherally enhancing lesions in the right frontal and temporal lobes, cerebellum, and lower pons (Fig. 2). Thoracentesis was performed and pleural fluid studies revealed an exudative pleural effusion with white blood cell (WBC) count of 3,559/mm3, red blood cell (RBC) count of 49,234/mm3, glucose of 4 mg/dL, and lactate dehydrogenase (LDH) of 1860 U/L. Pleural fluid studies were negative for bacterial or fungal growth, but culture-positive for Mycobacterium tuberculosis (MTB) and contained elevated levels of adenosine deaminase 18.7 U/L (reference range 0.0-9.4 U/L). A nucleic acid amplification test revealed no MTB resistance to rifampin. The patient also underwent lumbar puncture and cerebrospinal fluid (CSF) studies revealed WBC 2/mm3, RBC 11/mm3, total protein 47 mg/dL, and glucose 47 mg/dL. His CSF showed negative growth for bacteria, virus, fungus, or acid-fast bacilli (AFB). Blood cultures were negative for bacterial growth and a transthoracic echocardiogram was negative for vegetations. Electroencephalogram was normal.
A rheumatologic laboratory workup was also performed. Although the patient tested positive for anti-nuclear antibodies (ANA) and antibodies against chromatin, he had negative antibodies against Smith (Sm), double stranded DNA (dsDNA), Jo-1, ribonucleoprotein (RNP), rheumatoid factor (RF), cyclic citrullinated peptide (CCP), Sjogren's-syndrome-related antigens A and B (SSA/Ro and SSB/La), and centromere. He also tested negative for cytoplasmic and perinuclear-antineutrophil cytoplasmic antibodies (c-ANCA and p-ANCA).
On hospital day four, the patient received the diagnosis of active CNS TB manifesting as tuberculomas after his pleural fluid tested AFB smear-positive, and after alternative etiologies were ruled out as the cause of his seizure. He was promptly started on rifampin, isoniazid, pyrazinamide, ethambutol (RIPE), and vitamin B6. Levetiracetam was also initiated the day of admission for seizure prophylaxis. Throughout his stay, the patient remained hemodynamically stable and had no additional seizures nor neurological deficits. After two weeks of inpatient monitoring, the patient was discharged to undergo RIPE therapy for two months, followed by rifampin and isoniazid maintenance therapy. Repeat brain MRI at 6 months showed nearly complete resolution of most of the lesions; the pontine lesion decreased in size from 12 mm to 0.4 mm.