In a woman with acute transverse myelitis, thoracic sensory level, spinal cord MRI enhancement from T2‑T7, a lung mass, and CSF lymphocytic pleocytosis with markedly elevated protein, which antibody is most likely present?

Anti-Hu Antibody is Most Likely Present

In this woman with acute transverse myelitis, a thoracic sensory level at T2, patchy spinal cord enhancement from T2-T7, a lung mass, and CSF showing lymphocytic pleocytosis with markedly elevated protein (135 mg/dL), anti-Hu antibodies are most likely present, indicating paraneoplastic encephalomyelitis associated with small cell lung cancer. 1

Clinical Reasoning

This presentation is classic for paraneoplastic neurologic syndrome rather than the other options listed:

Why Anti-Hu (Paraneoplastic Encephalomyelitis):

• Lung mass + myelitis combination: Paraneoplastic encephalomyelitis and sensory neuropathy are caused by anti-Hu antibodies that cross-react with both small cell lung carcinoma antigens and human neuronal RNA-binding proteins, resulting in multiple neurologic deficits including myelopathy 1

• CSF profile matches: The lymphocytic pleocytosis with markedly elevated protein (135 mg/dL) is consistent with paraneoplastic syndromes, where CSF typically shows inflammatory changes 1

• Patchy enhancement pattern: The patchy enhancement from T2-T7 spanning multiple vertebral segments is characteristic of inflammatory/paraneoplastic myelitis rather than the longitudinally extensive transverse myelitis (≥3 vertebral segments with confluent enhancement) seen in neuromyelitis optica 1

• Small cell lung cancer association: SCLC is strongly associated with paraneoplastic neurologic syndromes including Lambert-Eaton syndrome, encephalomyelitis, and sensory neuropathy, all mediated by anti-Hu antibodies 1

Why NOT the Other Options:

HTLV-1: Would cause tropical spastic paraparesis/HTLV-1-associated myelopathy, but this presents with a more chronic, progressive course over months to years, not acute onset. The lung mass would be coincidental and unexplained 2

Aquaporin-4 (NMO-IgG): While this causes neuromyelitis optica with transverse myelitis, the MRI pattern is wrong. NMO typically shows longitudinally extensive transverse myelitis affecting ≥3 vertebral segments with confluent "cloud-like enhancement," not patchy enhancement 1. Additionally, NMO is not associated with lung masses 2

Enterovirus D68: Causes acute flaccid myelitis primarily in children, typically affecting the anterior horn cells (gray matter) of the cervical and thoracic cord, presenting with asymmetric flaccid paralysis. The sensory level and patchy white matter enhancement pattern here are inconsistent 1

Diagnostic Workup Recommendations

Immediate testing should include:

• Serum and CSF paraneoplastic antibody panel including anti-Hu, anti-Yo, anti-Ri, and anti-CRMP5, as paraneoplastic syndromes require both serum and CSF testing for optimal sensitivity 1, 3

• CT chest with contrast to characterize the lung mass, as SCLC is the most common malignancy associated with anti-Hu antibodies 1

• Brain MRI with contrast to evaluate for additional CNS involvement, as paraneoplastic encephalomyelitis can affect multiple CNS regions 1

• Comprehensive autoimmune encephalitis panel including anti-NMDAR, anti-VGKC complex, anti-LGI1, and anti-CASPR2 to exclude other antibody-mediated syndromes 1, 3

Critical Management Considerations

Treatment priorities:

• Tumor therapy is essential and the first priority, as response to cancer therapy favorably affects the course of paraneoplastic neurologic syndromes 4

• Initiate high-dose corticosteroids (methylprednisolone 1 g IV daily for 3-5 days) while awaiting antibody results, as early immunosuppressive treatment improves outcomes 1, 3

• Consider IVIg (0.4 g/kg/day for 5 days) or plasma exchange if inadequate response to steroids, particularly given the severity of presentation with 2/5 strength 1, 4

• Neurology consultation is mandatory for coordinated management of both the paraneoplastic syndrome and underlying malignancy 1

Prognostic Factors

Poor prognostic indicators present in this case:

• Abnormal spinal cord imaging with patchy enhancement correlates with worse outcomes in transverse myelitis 5
• Severe motor deficit (2/5 strength) at onset predicts poorer recovery 5
• Paraneoplastic neurologic syndromes, along with myocarditis, have higher fatality rates than other immune-related adverse events 1

Common pitfall: Delaying treatment while awaiting antibody results. Paraneoplastic antibody testing can take weeks, and neurologic damage may become irreversible. Empiric immunotherapy should be initiated immediately based on the clinical presentation of myelitis plus lung mass 1, 3