Sensory Neuronopathy

Sensory neuronopathy (ganglionopathy) is a disorder of the dorsal root ganglion neurons, causing asymmetric, non-length-dependent sensory loss with severe sensory ataxia and pseudoathetosis, with preserved strength. It is distinct from length dependent sensory neuropathy.

It is rare, with an estimated incidence of under 1 in every 100,000 people each year. Onset is usually in adult life, and the causes include autoimmune, paraneoplastic and toxic conditions.

Causes. Paraneoplastic (anti-Hu, particularly with small cell lung cancer), Sjögren syndrome, autoimmune and idiopathic forms, chemotherapy (cisplatin, oxaliplatin, paclitaxel), pyridoxine toxicity, HIV, hepatitis C, varicella zoster, and hereditary causes (mitochondrial, Friedreich ataxia).

Course. Subacute and progressive in paraneoplastic disease, and slowly progressive in Sjögren syndrome and idiopathic disease; toxic forms may partly recover after stopping the agent.

Pathophysiology.

Immune attack, direct toxicity or genetic injury destroys dorsal root ganglion neurons, with secondary degeneration of central and peripheral sensory axons.

The loss is permanent when neurons die, so early treatment of reversible causes is critical.

• Patchy, asymmetric numbness and paraesthesia of face, trunk, arms and legs, often beginning in the arms.
• Severe sensory ataxia: loss of joint position sense, pseudoathetosis, a positive Romberg test and wide based gait.
• Areflexia, preserved strength and normal cognition.
• Neuropathic pain; autonomic involvement and sicca symptoms in some.
• Systemic features of the underlying cause, such as weight loss and cough.

Red flags.

• Rapid progression with weight loss, smoking history or cough (paraneoplastic).
• Cerebellar, limbic or autonomic features (paraneoplastic encephalomyelitis).
• Exposure to vitamin B6 in high doses or chemotherapy.

• Clinical diagnosis from the pattern, supported by nerve conduction studies showing reduced or absent sensory nerve action potentials with normal motor studies.
• Antibodies: anti-Hu (ANNA-1), CV2/CRMP5, amphiphysin, antinuclear antibodies, extractable nuclear antigens (anti-Ro and anti-La), rheumatoid factor and cryoglobulins.
• MRI of the spine may show dorsal column T2 hyperintensity; lip biopsy or Schirmer testing for Sjögren syndrome.
• Whole body imaging (CT or PET) for occult cancer, repeated if negative; bronchoscopy as needed.
• Blood tests: B12, B6, copper, HIV, hepatitis, serum protein electrophoresis; cerebrospinal fluid analysis.

Differential diagnosis. Length dependent polyneuropathy, chronic inflammatory demyelinating polyneuropathy, subacute combined degeneration, Friedreich ataxia, tabes dorsalis, multiple sclerosis, spinal cord lesions and functional sensory loss.

• Treat the cause: stop neurotoxic chemotherapy or pyridoxine; treat cancer (the best treatment for paraneoplastic disease); treat infection.
• Immunotherapy for autoimmune and paraneoplastic disease within weeks of onset: methylprednisolone 1000 mg intravenously once daily for 3 to 5 days. Maximum 5 g in a course. Monitor blood pressure, glucose, mood, infection and gastric protection. Avoid with active untreated infection; use caution in diabetes, peptic ulcer and psychosis.
• Intravenous immunoglobulin 2 g/kg in total over 2 to 5 days, repeated every 4 to 8 weeks if there is benefit. Maximum 2 g/kg in any 4 week period. Monitor renal function, thrombosis, hypersensitivity and aseptic meningitis; check IgA before the first dose. Avoid in IgA deficiency with anti-IgA antibodies; use caution in renal impairment and heart failure.
• Longer term immunosuppression (rituximab or cyclophosphamide) in Sjögren syndrome and severe disease, through a specialist.
• Rehabilitation: physiotherapy, visual compensation, gait aids, home safety and occupational therapy.
• Neuropathic pain: pregabalin 75 mg orally twice daily, increased after 1 week to 150 mg twice daily, then to a maximum of 300 mg twice daily (600 mg daily). Monitor sedation, weight gain, oedema, mood and misuse. Adjust for renal function: creatinine clearance 30 to 59 mL/min, 75 to 300 mg daily; 15 to 29 mL/min, 25 to 150 mg daily; under 15 mL/min, 25 to 75 mg daily. Avoid in pregnancy unless benefit outweighs risk.
• Foot and joint protection from unnoticed injury.

Monitoring. Review at 4 to 6 weeks, then every 3 months; repeat tumour screening for 2 to 4 years in suspected paraneoplastic disease; track disability.

Referral and escalation. Neurology and oncology urgently when paraneoplastic disease is suspected; rheumatology for Sjögren syndrome.

Special groups. Pregnancy: avoid pregabalin and cyclophosphamide where possible. Older adults: falls prevention is the priority.