Polyneuropathies

Peripheral neuropathy is common, often distressing, and sometimes disabling or even fatal. The prevalence is about 24 per 1000, rising with age to 80 per 1000.¹ Most polyneuropathies are chronic and usually develop over several months. Three main patterns of polyneuropathy can be distinguished and each has a different differential diagnosis:

• Acute symmetrical peripheral neuropathy
• Chronic symmetrical peripheral neuropathy
• Multiple mononeuropathy

Both peripheral and cranial nerves are affected either by axonal degeneration (nerve becomes electrically inert within one week) or demyelination, which initially leaves the axon intact and results in blockage or slowing of conduction.

Patients with polyneuropathy may present with altered sensation, pain, weakness, or autonomic symptoms.

• Acute symmetrical polyneuropathy, e.g. Guillain-Barre syndrome, is uncommon. Acute multiple mononeuropathy requires urgent assessment as the commonest cause is vasculitis and prompt treatment with steroids, with or without cyclophosphamide, may prevent further irreversible nerve damage
• In sensory polyneuropathy, usually, the feet are affected first. Paraesthesiae, numbness, burning pain, and loss of vibration sense and position sense are prominent. Muscle wasting may occur. The sensory neuropathy may be subacute with ataxia caused by loss of sense of posture
• Predominantly motor peripheral neuropathies include Guillain-BarrT syndrome, Charcot-Marie-Tooth disease, porphyria, lead poisoning and diphtheria
• Possible causes of painful peripheral neuropathy include alcoholic neuropathy, diabetic amyotrophy, porphyria, vitamin B1 or B12 deficiency and carcinoma
• Polyneuropathy often affects the autonomic nervous system. Typical symptoms are constipation, loss of bowel or bladder control, orthostatic hypotension, the skin may become pale and dry, and sweating may be reduced
• Hereditary causes of polyneuropathy may also cause hammer toes, high arches, and scoliosis

The cause of chronic polyneuropathy is often unknown. The most common causes of peripheral neuropathy are:

• Diabetic neuropathy
• Nutritional, including alcohol (with or without vitamin B1 deficiency), B12 deficiency

Others causes include:

• Heavy metal poisoning, e.g. lead, mercury
• Infection, e.g. HIV, leprosy, diphtheria, tetanus, botulism
• Malignancy, e.g. carcinoma of the lung, carcinoma of the breast, myeloma
• Metabolic, e.g. hypothyroidism, liver failure, renal failure, acute intermittent porphyria
• Chronic vascular disease, e.g. polyarteritis nodosa, systemic lupus erythematosus
• Chronic inflammatory demyelinative polyneuropathy
• Postinfective polyneuritis, e.g. Guillain-Barre syndrome
• Sarcoidosis
• Drugs, e.g. isoniazid, vincristine, phenytoin, nitrofurantoin, gold and excess amounts of vitamin B6 (pyridoxine)
• Congenital, e.g. Charcot-Marie-Tooth, Friedreich's ataxia, Refsum's disease, Fabry's disease

Initial tests include:

• Urine: glucose, protein
• Haematology: full blood count, ESR, vitamin B12, folate
• Biochemistry: fasting glucose, renal function, liver function and thyroid function

Further investigations will depend on the outcome of clinical assessment and initial investigation results:

• Neurophysiology testing with assessment of distal and proximal nerve stimulation; electrophysiological procedures are helpful in determining the pathological process which may be either an axonopathy, a myelinopathy or a neuronopathy.²
• Biochemistry: Serum protein electrophoresis, serum angiotensin converting enzyme
• Immunology: Antinuclear factor, antiextractable nuclear antigen antibodies (anti-Ro, anti-La), antineutrophil cytoplasmic antigen antibodies
• Urine: Bence-Jones protein
• Cerebrospinal fluid: Cells, protein, immunoglobulin oligoclonal bands
• Immunology: Ati-HIV antibodies, antineuronal antibodies (Hu, Yo), antigliadin antibodies, serum angiotensin converting enzyme, antiganglioside antibodies, antimyelin associated glycoprotein antibodies
• Search for carcinoma, lymphoma, or solitary myeloma
• Molecular genetic tests, e.g. for Charcot-Marie-Tooth
• Nerve biopsy may be required

• Preventive and palliative treatments include foot care, weight reduction, sensible footwear and foot orthoses
• Patients with severe leg weakness may need walking aids
• Simple wrist splints can help weak wrist extension
• Disabled patients require help from a multidisciplinary team including an occupational therapist and a physiotherapist

Drugs

• Specific treatment depends on the cause
• Good control of glucose and blood pressure in patients with diabetes may improve or at least slow the progress of neuropathy.
• Chronic inflammatory demyelinative polyneuropathy is treatable with corticosteroids, intravenous immunoglobulin, plasma exchange, and some immunosuppressant drugs.³
• Multifocal motor neuropathy, responds to intravenous immunoglobulin,⁴ and possibly immunosuppressant drugs but not to corticosteroids or plasma exchange.
• No specific treatment is available for chronic idiopathic axonal polyneuropathy.
• Painful neuropathy is difficult to treat. The most useful drugs are anticonvulsants, especially gabapentin and carbamazepine, and tricyclic antidepressants, especially amitriptyline. Opioid drugs may be required.⁵

• With loss of sensation, recurrent injury to joints may lead to permanent joint destruction (Charcot's joint)
• May lead to disability, social isolation or loss of independence, especially in the elderly