Paraneoplastic Myelopathy

Paraneoplastic myelopathy is subacute progressive spinal cord dysfunction associated with cancer, caused by immune attack, and not by metastasis or treatment. It is rare. Syndromes include necrotising myelopathy, longitudinally extensive transverse myelitis and neuromyelitis optica spectrum disorder (anti-aquaporin-4), anti-CRMP5 (CV2) myelopathy, anti-amphiphysin myelopathy, stiff person syndrome, and subacute motor neuronopathy (lymphoma).

Associated tumours include small cell lung cancer, breast cancer, lymphoma, ovarian cancer and thymoma.

Pathophysiology. Antibody and T-cell responses to antigens shared between tumour and cord damage grey and white matter, and may produce necrosis.

Subacute, progressive paraparesis or quadriparesis over weeks to months, sensory level, bladder and bowel dysfunction, and spasticity, often with other paraneoplastic features (encephalopathy, neuropathy, optic neuritis). In necrotising myelopathy, rapid ascending paralysis occurs.

Red flags.

• Rapidly progressive myelopathy in a patient with cancer or risk factors (smoker).
• Concurrent optic neuritis, or area postrema syndrome.

MRI of the spine shows long segment T2 hyperintensity (often tract specific, such as lateral columns in CRMP5) with or without enhancement, and exclude compression or metastasis. CSF shows mild pleocytosis, raised protein and oligoclonal bands. Serum and CSF antibody panel (aquaporin-4, MOG, CRMP5, amphiphysin, Hu, Ri). Search for cancer: CT chest, abdomen and pelvis, FDG-PET, mammography, testicular or pelvic imaging, repeated after 3 to 6 months. Exclude infection, vitamin B12 deficiency, copper deficiency and radiation myelopathy.

Differential diagnosis.

• Spinal metastasis and radiation myelopathy.
• Idiopathic transverse myelitis, multiple sclerosis and neuromyelitis optica spectrum disorder.
• Vitamin B12 deficiency, infection and spinal dural arteriovenous fistula.

Treat the tumour and start immunotherapy early.

Tumour therapy. Surgery, chemotherapy or radiotherapy with oncology.

Immunotherapy.

• Methylprednisolone 1 g IV daily for 3 to 5 days, then prednisolone taper.
• Plasma exchange (5 sessions) or intravenous immunoglobulin 0.4 g/kg daily for 5 days.
• Rituximab 1 g IV twice, 2 weeks apart, or cyclophosphamide 750 mg/m2 IV monthly for refractory disease.

Supportive care. Spasticity treatment (baclofen 5 mg three times daily, increased to 30 to 80 mg daily), bladder care, venous thromboembolism prophylaxis (enoxaparin 40 mg SC daily), pressure care and rehabilitation.

Prognosis. Variable. Necrotising myelopathy is often fatal. Antibody to surface antigen (aquaporin-4) responds better.

Monitoring. Neurological examination, MRI at 3 months and tumour surveillance.

Referral and escalation. Refer urgently to neurology and oncology.