Paraneoplastic Sensory Neuronopathy

Paraneoplastic sensory neuronopathy is a rare subacute inflammatory destruction of dorsal root ganglion neurons with cancer, typically with anti-Hu (ANNA-1) antibodies and small cell lung cancer (in 75%). Others are anti-CRMP5, anti-amphiphysin and cancers of breast, ovary and lymphoma.

Pathophysiology. Cytotoxic T cells and antibodies attack sensory neurons in dorsal root ganglia, giving irreversible loss of large and small sensory fibres.

Asymmetric, patchy numbness, burning pain and paraesthesia, evolving over weeks to months, involving the limbs, trunk and face. Loss of proprioception causes sensory ataxia, pseudoathetosis and areflexia, with preserved strength. Autonomic, limbic or cerebellar involvement may coexist.

Red flags.

• Subacute asymmetric sensory loss with ataxia in a smoker.
• Weight loss or cough.

Nerve conduction studies show absent or reduced sensory action potentials with normal motor studies. MRI of the spine may show dorsal column T2 hyperintensity. CSF shows mild pleocytosis and raised protein. Test serum for anti-Hu, CRMP5, amphiphysin and other onconeural antibodies. Search for cancer: CT chest, abdomen and pelvis, FDG-PET, and bronchoscopy if required, repeated at 3 to 6 months.

Differential diagnosis.

• Sjogren syndrome neuronopathy, cisplatin and pyridoxine toxicity.
• Vitamin B12 and E deficiency, HIV and chronic inflammatory neuropathy.
• Cerebellar ataxia with neuropathy and vestibular areflexia syndrome.

Treat the tumour, since outcomes depend on cancer control.

Tumour therapy. Chemotherapy, radiotherapy or surgery for small cell lung cancer and other cancer.

Immunotherapy. Response is limited, and early use gives best chances.

• Methylprednisolone 1 g IV daily for 3 to 5 days.
• Intravenous immunoglobulin 0.4 g/kg daily for 5 days, or plasma exchange.
• Cyclophosphamide 750 mg/m2 IV monthly or rituximab 1 g IV twice, 2 weeks apart, in selected cases.

Neuropathic pain. Gabapentin 300 mg daily, increased to 600 to 1200 mg three times daily (adjust to eGFR), or pregabalin 75 to 300 mg twice daily, or duloxetine 30 to 60 mg daily.

Rehabilitation. Balance and sensory re-education, walking aids and falls prevention.

Monitoring. Neurological function, and cancer surveillance for 4 years.

Referral and escalation. Refer to neurology and oncology.