12th August 2024

Metabolic and toxic neuropathies

Diabetic neuropathy

This can manifest in multiple different ways, the most common of which is a length-dependent (i.e. distal onset ‘glove-and-stocking’), symmetric, sensory-predominant neuropathy. Other forms include autonomic neuropathy, polyradiculopathies, cranial mononeuropathies (typically oculomotor nerve), and mononeuritis multiplex.

Alcoholic neuropathy

This symmetric distal-onset neuropathy is due to direct axonal toxicity, often complicated by nutritional deficiency causing demyelination. Sensory symptoms generally precede motor. Dry beriberi is a term used to describe a demyelinating polyneuropathy caused by thiamine deficiency, which may occur in the context of chronic alcohol misuse.

Porphyria

Acute intermittent porphyria (AIP) is a rare autosomal dominant metabolic disorder resulting from a deficiency of porphobilinogen deaminase. Most patients present in their 20-30s, and females are much more likely to manifest symptoms, though gene frequency is equal between males and females. Exacerbating factors include smoking, medications, stress and sex hormones.

The constellation of symptoms includes abdominal pain, vomiting, psychiatric symptoms, peripheral neuropathies (motor predominance), hypertension, tachycardia and hyponatraemia. Severe manifestations include seizures, quadriplegia and respiratory failure. In an acute attack, urine may turn deep red on exposure to light and is tested for elevated urinary porphobilinogen. Treatment is with haem arginate (hemin).

Porphyria cutanea tarda (PCT) is caused by reduced uroporphyrinogen decarboxylase activity. Presentation is generally with a photosensitive rash. In later stages of the disease, a liver impairment may be seen. Testing shows increased plasma and urine porphyrins.

Lead poisoning

This may cause a similar pattern of symptoms to porphyria. The blood lead level is used to guide whether chelation therapy with DMSA (dimercaptosuccinic acid) or EDTA (ethylenediaminetetraacetic acid) is indicated.

Drug-induced polyneuropathy

Many drugs may cause peripheral neuropathy. Some of the most strongly associated are listed here:

• Antimicrobials: fluoroquinolones, nitrofurantoin, metronidazole, isoniazid and dapsone
• Chemotherapy agents: vinca alkaloids, taxanes and platinum-based regimens
• TNF (tumor necrosis factor) or immune checkpoint inhibitors
• Phenytoin
• Amiodarone
• Colchicine