We describe a case illustrating a challenging diagnostic dilemma of Mycobacterium haemophilum infection in a woman with longitudinally extensive transverse myelitis and disseminated brain lesions.

A 22-year-old woman presented with bilateral leg weakness and T2 signal abnormalities throughout the thoracolumbar spinal cord with a single nodular region of enhancement. Peripheral T-spot, HIV, myelin oligodendrocyte glycoprotein antibody, and aquaporin 4 antibody were negative; CSF protein, cell count, and oligoclonal bands were normal. She had no TB risk factors. She was treated empirically for neuromyelitis optica spectrum disorder with three rounds of high dose methylprednisolone, monthly immunoglobulin, and rituximab. Over two months, she developed new lesions in the spinal cord and middle cerebellar peduncle, and later had multifocal enhancing lesions with tract-like appearance in the brainstem, deep grey nuclei, and bilateral cerebral hemispheres. Three brain biopsies demonstrated necrotizing granulomas and acid-fast staining bacilli; cultures were negative. Biopsies sent for PCR testing for bacterial, fungal and mycobacterial pathogens returned positive for M. haemophilum. She improved with intravenous rifampin, azithromycin, and moxifloxacin, and required a ventriculoperitoneal shunt for elevated intracranial pressures. Workup for immunodeficiencies is ongoing. 

Longitudinally extensive transverse myelitis, while most often associated with autoimmune processes, can occur in the context of mycobacterial or other infections. In antibody-negative cases, clinicians should be cautious when the clinical course does not align with typical autoimmune responses and should pursue alternative diagnostics for infections. While nontuberculous mycobacteria are rare causes of neurologic infections, their incidence is rising globally. Although diagnosing these infections can be difficult due to poor culture growth, timely identification is critical, as they often respond to appropriate antimicrobial treatment.