Metabolic, nutritional and toxic neuropathies
- Lesion
Kidney failure, low thyroid, missing vitamins, alcohol, cancer drugs and heavy metals can all damage nerves, usually starting at the feet.
What it is
Many systemic disorders cause a distal symmetric, mostly axonal polyneuropathy. Uraemia causes a length-dependent neuropathy and restless legs, improved by dialysis or transplant. Hypothyroidism and acromegaly cause entrapment (carpal tunnel). Deficiencies of thiamine (dry beriberi), vitamin B12 (with spinal cord damage), vitamin B6, vitamin E and copper, often linked to alcohol use, malabsorption or bariatric surgery, damage nerves, as does excess B6. Toxic neuropathies follow chemotherapy (vincristine, taxanes, platinum, bortezomib, thalidomide), other drugs (isoniazid, metronidazole, nitrofurantoin, amiodarone) and metals and chemicals (lead, arsenic, mercury, organophosphates, hexacarbons).
Structure
- Most: distal axonal degeneration with loss of large and small fibres.
- Lead and some toxins: mixed axonal and demyelinating changes.
- Cisplatin and pyridoxine excess: loss of dorsal root ganglion neurons (neuronopathy).
- Hexacarbons (glue sniffing): giant axons filled with neurofilaments.
Step by step
- Toxins and deficiencies impair axonal transport, mitochondria or microtubules.
- The longest axons, which depend most on transport, fail first at their distal ends.
- Distal axons degenerate in a 'dying back' pattern.
- Some agents attack the sensory neuron body directly, causing non-length-dependent sensory loss.
- If the cause is removed early, axons regrow slowly; neuronal death is permanent.
Selected metabolic, nutritional and toxic causes
| Cause | Mechanism | Clue |
|---|---|---|
| Vitamin B12 deficiency | Defective myelin and methylation | Dorsal column signs, megaloblastic anaemia |
| Thiamine deficiency (dry beriberi) | Failed energy metabolism | Alcohol use, malnutrition; Wernicke encephalopathy |
| Uraemia | Retained toxins | Restless legs; better with transplant |
| Vincristine, taxanes | Microtubule disruption | Dose-related numbness, constipation |
| Cisplatin | Dorsal root ganglion damage | Sensory ataxia, hearing loss |
| Lead | Motor axonal injury | Wrist drop, anaemia with basophilic stippling |
| Organophosphates | Delayed axonopathy | Weeks after cholinergic poisoning |
Clinical notes
- A basic work-up for neuropathy includes glucose or HbA1c, B12, kidney and thyroid function, and serum protein electrophoresis.
- In malnutrition and alcohol use disorder, thiamine is given before glucose to prevent Wernicke encephalopathy.
- Chemotherapy-induced neuropathy is a leading reason to change cancer treatment.
Test yourself
Think of the answer, then tap the question to see it.
Which vitamin deficiency causes neuropathy with dorsal column and corticospinal tract damage?
Vitamin B12 deficiency (subacute combined degeneration).
Why does isoniazid cause neuropathy?
It causes functional vitamin B6 deficiency; pyridoxine prevents it.
Which metal causes wrist drop?
Lead.
How does vincristine damage nerves?
It disrupts microtubules, impairing axonal transport and causing distal axonal degeneration.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Vitamin B12 deficiency anemia: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2025); Beriberi: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2025); Lead poisoning: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.