Lesions of Peripheral Nerves

Lesions of peripheral nerves

The various nerve fibre types within a peripheral nerve are shown in Table 18.50. All are myelinated except the C fibres, which carry impulses from pain receptors.

·  Mechanisms of damage to peripheral nerves

o  Demyelination

o  Axonal degeneration

o  Wallerian degeneration

o  Compression

o  Infarction

o  Infiltration

·  Nerve regeneration

·  Definitions

Mechanisms of damage to peripheral nerves

The peripheral nerve consists of two principal cellular structures – the axon, with its anterior horn cell, and the myelin sheath, which is produced by Schwann cells between each node of Ranvier. Blood supply is via vasa nervorum. Six principal mechanisms, some of which may coexist, cause malfunction of the nerve as a whole:

• demyelination

• axonal degeneration

• Wallerian degeneration

• compression

• infarction

• infiltration.

Demyelination

When the Schwann cell is damaged, the myelin sheath is disrupted, causing marked slowing of nerve conduction. This occurs in the Guillain–Barré syndrome, in the neuropathy which follows diphtheria, and in hereditary sensorimotor neuropathies, where there are defects in myelin production.

Axonal degeneration

Here the primary lesion affects the axon, which dies back from the periphery. Conduction velocity tends to remain normal because axonal continuity is maintained in surviving fibres. Axonal degeneration occurs typically in toxic neuropathies.

Wallerian degeneration

This describes changes following section of a nerve. The axon and the distal myelin sheath degenerate, over the course of several weeks.

Compression

This causes focal, also called segmental demyelination at the point of compression with disruption of the myelin sheath. This occurs typically in entrapment neuropathies such as the carpal tunnel syndrome.

Infarction

Microinfarction of vessels supplying the nerve occurs in arteritis, such as polyarteritis nodosa, and in diabetes. Wallerian degeneration occurs distal to the focal area of ischaemia.

Infiltration

Peripheral nerves are infiltrated by inflammatory cells in sarcoidosis or leprosy, or by malignant cells.

Nerve regeneration

Regeneration occurs either by remyelination, when recovering Schwann cells spin new myelin sheaths around the axon, or by axonal growth down the nerve sheath and axonal sprouting from the stump. Axonal growth takes place at a rate of up to 1 mm daily. In a chronic polyneuropathy, sprouts from terminal axons of normal motor axons reinnervate denervated muscle fibres; giant polyphasic units are then seen on electromyography.

Definitions

• Neuropathy means a pathological process affecting a peripheral nerve or nerves.

•Mononeuropathy is a process affecting a single nerve.

•Mononeuritis multiplex (multiple mononeuropathy) is a process affecting several or multiple nerves.

•Polyneuropathy is a diffuse, symmetrical disease process, usually progressing proximally. It is either acute, subacute or chronic and the course progressive, relapsing or towards recovery. Polyneuropathy may be motor, sensory, sensorimotor (i.e. mixed) or autonomic. Polyneuropathies are classified broadly into demyelinating and axonal types, depending upon which principal pathological process predominates. It is often not possible to separate these varieties clinically.

•Radiculopathy means a disease process affecting the nerve roots.

Mononeuropathies

·  Peripheral nerve compression or entrapment

·  Carpal tunnel syndrome

·  Ulnar nerve compression

·  Radial nerve compression

·  Meralgia paraesthetica

·  Common peroneal nerve palsy

·  Mononeuritis multiplex (multiple mononeuropathy)

Peripheral nerve compression or entrapment

See Table 18.51

Damage to a nerve by compression is either acute (e.g. due to a tourniquet or other sustained pressure) or chronic, such as in entrapment neuropathy. In both, demyelination predominates, but some axonal degeneration occurs.

Acute compression usually affects nerves which are exposed anatomically (e.g. the common peroneal nerve at the head of the fibula). Entrapment develops where a nerve passes through relatively tight anatomical passages (e.g. the carpal tunnel).

These conditions are diagnosed largely from the clinical features. Diagnosis is confirmed by nerve conduction studies and electromyography. The most common conditions are mentioned below. All are more common in people with diabetes. In countries where leprosy is prevalent, such as in India, this disease is a cause of an apparently isolated nerve lesion, which, if seen in the UK, would be likely to be caused by compression or entrapment.

Carpal tunnel syndrome

(p. 456)

This is the common condition of median nerve compression at the wrist. Many cases are idiopathic, but this entrapment neuropathy is sometimes seen in:

• hypothyroidism

• diabetes mellitus

• pregnancy and obesity

• rheumatoid arthritis

• acromegaly.

There is nocturnal tingling and pain in the hand (and sometimes forearm) followed by weakness of the thenar muscles. Wasting of abductor pollicis brevis develops, with sensory loss of the palm and radial three-and-a-half fingers. Tinel’s sign may be positive, i.e. tapping on the carpal tunnel will reproduce the pain.

Treatment with a splint at night or a local steroid injection in the wrist gives temporary relief. When the condition occurs in pregnancy, owing to fluid retention, it is often self-limiting. Surgical decompression of the carpel tunnel is a simple and definitive treatment.

Ulnar nerve compression

This typically occurs at the elbow, where the nerve is compressed in the cubital tunnel. It follows fracture of the ulna or prolonged or recurrent pressure on the nerve at this site.

Wasting of the ulnar-innervated muscles develops (hypothenar muscles and interossei) together with sensory loss in the ulnar one-and-a-half fingers.

Decompression and transposition of the nerve at the elbow may be necessary.

The deep, solely motor, branch of the ulnar nerve may be damaged in the palm by recurrent pressure from tools, e.g. a screwdriver, crutches or cycle handlebars.

Radial nerve compression

The radial nerve is compressed acutely against the humerus, such as when the arm is draped over a hard chair for several hours (‘Saturday night palsy’). Wrist drop and weakness of finger extension and of brachioradialis follow. Recovery is usual within 1–3 months.

Meralgia paraesthetica

Entrapment of the lateral cutaneous nerve of the thigh beneath the inguinal ligament causes burning, tingling and numbness on the anterolateral aspect of the thigh. Many patients are obese; weight reduction helps to relieve the symptoms. Division of the inguinal ligament is not usually effective.

Common peroneal nerve palsy

When the common peroneal (lateral popliteal) nerve is compressed against the head of the fibula, following prolonged squatting, wearing a plaster cast, prolonged bedrest or coma, there is foot drop and weakness of ankle eversion. Frequently no cause is found. A patch of numbness on the anterolateral border of the shin or dorsum of the foot develops. Recovery is usual, though not invariable, within several months.

Mononeuritis multiplex (multiple mononeuropathy)

Mononeuritis multiplex occurs in:

• diabetes mellitus

• leprosy (still the most common worldwide cause)

• vasculitis

• sarcoidosis

• amyloidosis

• malignancy

• neurofibromatosis

• HIV infection.

Diagnosis is largely clinical, supported by electrical studies. Several nerves become affected, for example sequential involvement of an ulnar nerve, a lateral popliteal and radial, over the course of some weeks. When mononeuritis multiplex is symmetrical, there may be difficulties separating it clinically from polyneuropathy. Treatment is that of the underlying disease.

Polyneuropathies

Many toxins and disease processes are known to be associated with polyneuropathy (see below), though the cause of the majority of cases remains undetermined. The most common presentation is a chronic or subacute sensorimotor neuropathy. A classification of poly-neuropathy is given in Table 18.52.

·  Guillain–Barré syndrome (acute inflammatory or postinfective polyneuropathy)

·  CLINICAL FEATURES

·  DIAGNOSIS

·  COURSE AND MANAGEMENT

·  Chronic inflammatory demyelinating polyneuropathy (CIDP)

·  Diphtheritic neuropathy

·  Idiopathic chronic sensorimotor neuropathy

·  Cranial polyneuropathy

·  Metabolic, toxic and vitamin-deficiency neuropathies

·  Metabolic neuropathies

o  Diabetes mellitus

o  Uraemia

o  Thyroid disease

o  Porphyria

o  Amyloidosis

o  Refsum’s disease

·  Toxic neuropathies

o  Alcohol

o  Drugs

o  Industrial toxins

·  Vitamin-deficiency neuropathies

o  Thiamin (vitamin B1)

o  Wernicke–Korsakoff syndrome

o  Pyridoxine (vitamin B6)

o  Vitamin B12 (cobalamin)

o  Subacute combined degeneration of the cord

·  Hereditary sensorimotor neuropathies (HMSN)

·  Peroneal muscular atrophy

·  HMSN type III

·  Other polyneuropathies

·  Neuropathy in cancer

·  Neuropathies with systemic diseases and vasculitis

o  The POEMS syndrome

·  Autonomic neuropathy

Guillain–Barré syndrome (acute inflammatory or postinfective polyneuropathy)

CLINICAL FEATURES

This demyelinating neuropathy, which is the most common recognizable acute neuropathy, has an autoallergic basis. It follows 1–3 weeks after infection that is often trivial, and rarely identified. Campylobacter infection is, however, a recognized cause of GBS. The patient complains of weakness of distal limb muscles and/or distal numbness. This ascends over several days or over a period up to three weeks. In mild cases there is little disability, before spontaneous recovery begins, but in some 20% of cases the respiratory and facial muscles are affected and the patient may become paralysed.

Weakness, areflexia and sensory loss are found in an ascending pattern from the fingers and toes.

Autonomic features (see below) are sometimes seen. There is a rare proximal form of the condition that initially affects the ocular muscles and in which ataxia is found (Miller–Fisher syndrome).

DIAGNOSIS

This is established on clinical grounds and is confirmed by nerve conduction studies, which show the slowing of conduction, prolonged distal motor latency and/or conduction block seen in demyelinating neuropathies. The CSF contains a normal cell count and sugar level but the protein is frequently raised to 1–3 g L–1.

The differential diagnosis includes other paralytic illnesses such as poliomyelitis, botulism or primary muscle disease.

COURSE AND MANAGEMENT

In the untreated case, recovery begins to take place after the initial period of progression of up to three weeks. However by this time, paralysis may be so severe as to require assisted ventilation. It is essential, even in the early stages, that particular attention be paid to measuring ventilatory function (vital capacity, blood gases) repeatedly and recognizing the development of weakness of bulbar muscles. Prolonged assisted ventilation may be necessary. Subcutaneous heparin should be given to reduce the risk of venous thrombosis.

High-dosage intravenous -globulin reduces the duration and severity and should be given to all patients. Serum of patients should be screened for IgA deficiency before -globulin is given – severe allergic reactions due to IgG antibodies may occur if this congenital deficiency is present.

Plasmapheresis is also of proven benefit in shortening the period of disability. Corticosteroids have been used to treat the Guillain–Barré syndrome but are not of proven value in improving the outcome.

Recovery, though gradual over many months, is usual but may be incomplete.

Chronic inflammatory demyelinating polyneuropathy (CIDP)

This condition, recognized in the 1980s, is a polyneuropathy which develops over weeks or months, usually with a relapsing and remitting course. CSF protein is raised and segmental demyelination is seen in peripheral nerves, with Schwann cells arranged in lamellae resembling an onion skin – hence the pathological term, onion bulbs. The neuropathy responds to steroids and to -globulin, which is used in exacerbations. There is particular interest in this neuropathy because, in some cases, plaques resembling MS lesions are seen on MRI, in both the brain and spinal cord.

The outlook is variable, but many cases, with steroid therapy run a benign course over many years. Recovery occasionally occurs.

There are several other varieties of this condition – the classical demyelinating form, an axonal form, and mononeuritis multiplex.

Diphtheritic neuropathy

Demyelinating neuropathy is caused by the exotoxin of Corynebacterium diphtheriae (see p. 24). Palatal weakness followed by pupillary paralysis and a sensorimotor neuropathy occur several weeks after faucial infection. The condition is now rare in countries where immunization against diphtheria is practised efficiently.

Idiopathic chronic sensorimotor neuropathy

The patient complains of a progressive symmetrical numbness and tingling in the hands and feet, which spreads proximally in a glove and stocking distribution. There is distal weakness, which also ascends. Rarely the cranial nerves are affected. Tendon reflexes involving affected nerves are lost. The symptoms may progress over many months, remain static or remit at any stage. Autonomic features are sometimes seen.

Investigation (nerve conduction studies and electromyography) shows either axonal degeneration or demyelination, or features of both these processes. Peripheral nerve biopsy is also helpful in classifying these cases, some of which are diagnosed as chronic inflammatory demyelinating polyneuropathy (see above).

Cranial polyneuropathy

This describes simultaneous or sequential cranial nerve lesions, which occur in malignant infiltration, particularly with lymphomas, and in sarcoidosis

Metabolic, toxic and vitamin-deficiency neuropathies

The most common of these neuropathies are shown in Table 18.53. All are due to impairment of normal metabolism of the axon, myelin or both.

Metabolic neuropathies

Diabetes mellitus

Several varieties of neuropathy occur in diabetes mellitus:

• symmetrical sensory polyneuropathy

• acute painful neuropathy

• mononeuropathy and multiple mononeuropathy:

cranial nerve lesions

isolated peripheral nerve lesions (e.g. median)

• diabetic amyotrophy

• autonomic neuropathy.

These are discussed in more detail on see p. 982.

Uraemia

Progressive sensorimotor neuropathy occurs in chronic uraemia. The response to dialysis is variable but the neuropathy usually improves after renal transplantation.

Thyroid disease

A mild chronic sensorimotor neuropathy is sometimes seen in both hyperthyroidism and hypothyroidism (see pp. 937 and 932). Myopathy also occurs in hyperthyroidism (p. 937).

Porphyria

Acute intermittent porphyria is a rare metabolic disorder (see p. 1003) in which there are episodes of a severe, mainly proximal, neuropathy, sometimes associated with abdominal pain, confusion and later coma. Alcohol and barbiturates may precipitate attacks.

Amyloidosis

This is described on p. 1002. Either a polyneuropathy or a multineuritis multiplex occurs.