Nutritional Polyneuropathy

Nutritional polyneuropathy is a symmetric, length dependent neuropathy from deficiency of vitamins and nutrients, including thiamine (beriberi), vitamin B12, folate, vitamin B6 (deficiency and excess), vitamin E, copper and niacin. Risk groups are people with malnutrition, bariatric surgery, malabsorption (coeliac disease, inflammatory bowel disease), alcohol use, strict vegan diets without supplements, restrictive eating, long term proton pump inhibitor or metformin use, and prolonged parenteral nutrition.

Pathophysiology. Deficiency impairs myelin synthesis, axonal energy metabolism and neurotransmitter production, causing axonal degeneration and sometimes myelopathy.

Numbness, burning, paraesthesia and weakness in the feet and legs, loss of vibration and proprioception, sensory ataxia and reduced reflexes. Vitamin B12, copper and vitamin E deficiency may cause myelopathy with spasticity, and optic neuropathy. Thiamine deficiency causes dry beriberi (neuropathy) or wet beriberi (heart failure) and Wernicke encephalopathy. Pellagra causes dermatitis, diarrhoea and dementia.

Red flags.

• Confusion, ophthalmoplegia or ataxia (Wernicke).
• Subacute combined degeneration with spasticity.
• Heart failure with neuropathy.

Measure vitamin B12 (with methylmalonic acid and homocysteine if borderline), folate, thiamine (erythrocyte transketolase or whole blood), vitamin B6, vitamin E, copper and caeruloplasmin, zinc, full blood count (macrocytosis or anaemia), coeliac serology, glucose and thyroid function. Nerve conduction studies show axonal neuropathy. MRI of spine for suspected myelopathy (dorsal column T2 hyperintensity). Assess diet, surgery and drugs.

Differential diagnosis.

• Diabetic, alcoholic and uraemic neuropathy.
• Toxic and drug induced neuropathy, paraproteinaemic neuropathy and HIV neuropathy.
• Hereditary neuropathy and nitrous oxide related myeloneuropathy.

Replace the deficiency early, since recovery is limited if treatment is delayed.

Thiamine. 100 mg orally three times daily for beriberi neuropathy, and 500 mg IV three times daily for 2 to 3 days if Wernicke encephalopathy is possible, before glucose.

Vitamin B12. Hydroxocobalamin 1 mg IM on alternate days until no further improvement, then 1 mg every 2 months (or 1 mg IM three times weekly for neurological involvement for 2 weeks). Oral cyanocobalamin 1000 microgram daily if the cause is dietary.

Folate. Folic acid 5 mg daily, given only after B12 deficiency has been excluded or treated.

Vitamin E. 100 to 400 mg daily in deficiency, and higher doses in malabsorption.

Copper. 8 mg elemental copper daily orally for 1 week, then 4 mg daily for a week, then 2 mg daily (IV copper for severe disease). Stop excess zinc.

Vitamin B6. Stop excess supplements, and give 50 mg daily in deficiency.

Niacin. Nicotinamide 300 to 500 mg daily in divided doses.

Underlying cause. Treat malabsorption, review drugs (metformin, proton pump inhibitor), nutrition support and dietitian input. Bariatric patients need lifelong supplements.

Pain and rehabilitation. Gabapentin or amitriptyline, physiotherapy and foot care.

Monitoring. Repeat levels at 1 to 3 months, and neurological recovery over 6 to 12 months.

Referral and escalation. Refer to neurology and dietitian.

Special groups. In pregnancy, give folic acid and B12 as needed.