Paraneoplastic myelitis

Paraneoplastic myelitis is a diverse group of spinal cord disorders caused by mechanisms unrelated to metastases, infections, coagulopathy, or metabolic issues. It leads to rapidly progressive spastic paresis and can involve other parts of the nervous system. Commonly associated antibodies include anti-Hu, anti-CRMP5, and anti-amphiphysin antibodies, with a strong association with small cell lung cancer (SCLC) and other malignancies. Treatment focuses on removing the tumor source and suppressing the immune response. Plasma exchange or intravenous immune globulin (IVIG) may be used initially, followed by glucocorticoids, cyclophosphamide, or rituximab if needed. Early tumor identification and management can stabilize or improve the neurological syndrome.

Understanding Paraneoplastic Myelitis

Paraneoplastic myelitis is a group of disorders impacting the spinal cord due to immune-mediated mechanisms linked to cancer, rather than direct metastases or infections. It often presents with rapidly progressive spastic paresis, sometimes accompanied by bowel and bladder dysfunction. This condition can co-occur with encephalitis, sensory neuronopathy, motor neuronopathy, autonomic dysfunction, or stiff-person syndrome. Commonly associated antibodies include anti-Hu, anti-CRMP5, and anti-amphiphysin, with small cell lung cancer (SCLC) being the most frequent underlying malignancy.

Therapeutic Approach

The primary therapeutic approach involves treating the underlying tumor and suppressing the immune response. This may include:

• Plasma Exchange: Typically, five exchanges over 7 to 14 days.
• Intravenous Immune Globulin (IVIG): Administered at 0.4 g/kg daily for five days.
• Glucocorticoids: For instance, methylprednisolone at 1 gram daily for five days.
• Cyclophosphamide: Administered at 750 mg/m2 monthly for four to six months.
• Rituximab: Given at 375mg/m2 weekly for 4 weeks.

Considerations for Specific Treatments

• Cyclophosphamide: Hold treatment if neutrophils are below 1.0 or platelets below 100. Dose adjustments are necessary for reduced creatinine clearance. For detailed guidelines, visit: http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Cyclophosphamide_monograph_1June2013_formatted.pdf. 
• Rituximab: Hold if neutrophils are below 1.0 or platelets below 100. Premedication with paracetamol, hydrocortisone, and chlorpheniramine is recommended. Assessment for progressive multifocal leucoencephalopathy is crucial. For more information, refer to: http://www.bccancer. bc.ca/drug-database-site/Drug%20Index/Rituximab_monograph.pdf

References

1. Allenbach Y, et al. High risk of cancer in autoimmune necrotizing myopathies.
2. McCabe DJH, et al. Paraneoplastic “stiff person syndrome” with metastatic adenocarcinoma and anti-Ri antibodies.
3. Richard S, et al. An immunologic syndrome featuring transverse myelitis after bone marrow transplant.
4. Giometto B, et al. Treatment for paraneoplastic neuropathies.
5. Leypoldt F, et al. Successful treatment of anti-Ri-associated paraneoplastic myelitis.
6. Sampson JB, et al. Paraneoplastic myopathy: response to intravenous immunoglobulin.