Peripheral neuropathies I: Clinical approach and investigations

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Peripheral neuropathies I

Clinical approach and investigations

Peripheral neuropathies are very variable, both in their clinical manifestations and in their aetiology (Table 1). These three sections give an overview of peripheral nerve disease, with the third concentrating on the common isolated peripheral nerve lesions.

Table 1 Relationship of presentation of neuropathy to aetiology

Pathology

Peripheral nerves can be affected in three ways (Fig. 1). These mechanisms of injury are not mutually exclusive and in some conditions there are contributions from all three mechanisms:

1. Axonal degeneration.

2. Demyelination.

3. Vascular nerve damage.

Fig. 1 Effects on peripheral nerve conduction of common neuropathies. (a) Normal; (b) axonal degeneration; (c) demyelination; (d) vascular lesion.

Axonal degeneration

The axon degenerates as a result of many different toxic, metabolic, nutritional and physical (such as cold or trauma) insults and in genetic conditions. The longest axons are most severely affected. These changes result in distal weakness, wasting or sensory loss depending on the involvement of motor and sensory fibres. If the neurone remains intact and the pathological process is reversed, there is scope for regeneration. If the neurone is lost, there is no scope for regeneration.

Demyelination

In this process, the myelin is lost but the axon is preserved. The demyelination prevents conduction and produces weakness but not wasting. Repair of demyelination, remyelination, can be quick. Many demyelinating neuropathies also have some associated axonal degeneration. Demyelination can occur in inflammatory diseases, when it tends to be patchy, and in inherited or metabolic neuropathies, when it tends to be uniform.

Vascular nerve damage

The blood supply to peripheral nerves can be disrupted, producing infarcts of peripheral nerves. This then produces isolated axonal degeneration in the axons distal to the site of infarct. This usually occurs with vasculitic illness.

Clinical features

Peripheral neuropathies can be sensory or motor, though usually there is a combination with one predominant. The clinical features depend on the underlying pathological process and the speed of onset. Axonal neuropathies result in wasting of muscles with loss of distal tendon reflexes. Demyelinating neuropathies are not associated with muscle wasting, but usually there is areflexia. In some types of neuropathy, the autonomic nervous system can also be affected.

There are four patterns of clinical presentation of peripheral nerve disease (Fig. 2):

1. Distal symmetrical neuropathy. This is the most common presentation of axonal neuropathies. There is distal sensory and motor dysfunction, affecting the legs more than the arms; sensory changes in the hands are noted when sensory changes in the legs get to the knees.

2. Multifocal neuropathies. There is an asymmetrical involvement, without involving specifically named nerves. This is usually the presentation of demyelinating or vasculitic neuropathies.

3. Mononeuropathies. The involvement of an individual named nerve. The most commonly affected nerves are described on page 106.

4. Mononeuritis multiplex. The involvement of multiple named nerves. This is relatively uncommon and is highly suggestive of a vasculitis.

Fig. 2 Clinical patterns of peripheral nerve involvement in vasculitic neuropathies.

The speed of onset can be divided into acute, less than 4 weeks, subacute, developing over 1–6 months, and chronic, developing over 6 months. This is useful in the diagnosis of aetiology.

Diagnosis and differential diagnosis

The diagnosis of a peripheral neuropathy falls into two parts.

Is it a peripheral neuropathy?

In most patients, this is straightforward, presenting with one of the clinical syndromes described above. There are a few difficult situations:

Patients with an acute-onset weakness of the arms and legs. The differential diagnosis here is between an acute neuropathy, usually Guillain–Barré syndrome, a cervical spinal cord or brain stem lesion, myasthenia gravis and an acute myopathy. Reflex changes, sensory findings and ancillary investigations including nerve conduction studies may be needed to clarify this. N.B. The most common and dangerous erroneous differential diagnosis given in patients with acute neuropathies is hysteria.

Patients with weakness and wasting in the limbs without sensory signs. The differential diagnosis lies between a predominantly motor neuropathy and anterior horn cell disease, such as amyotrophic lateral sclerosis and a myopathy. Neurophysiology may be needed to clarify matters.

What type of peripheral neuropathy is it?

This is a good example of different levels of diagnosis. For example, the clinical diagnosis could be of a chronic distal symmetrical sensorimotor neuropathy. Neurophysiology establishes this to be an axonal neuropathy, and further investigations find this to be a distal symmetrical axonal sensorimotor neuropathy – caused by diabetes.

The time course and pattern of clinical presentation along with the neurophysiological disturbance give an indication of likely aetiology, which needs to be confirmed by further investigations. This is summarized in Table 1.

Investigations

The investigations will be directed by the clinical presentation. Nerve conduction studies are essential in understanding the pattern of the neuropathy. Ancillary investigations are directed at establishing associations with the syndrome or finding the aetiology.

In a patient with an acute demyelinating neuropathy, finding an acellular CSF with raised protein is further corroboration of the diagnosis of Guillain–Barré syndrome.

A patient with an axonal distal sensorimotor neuropathy without a clinical indicator of aetiology will need a screen of investigations to look for systemic and deficiency states (Box 1).

The diagnosis of certain inherited neuropathies can now be made by finding the appropriate genetic abnormality using molecular genetics (see below). In other patients in whom there is apparently no family history of neuropathy, a diagnosis can be made by examining the patient’s relatives and finding other affected members.

A patient with possible vasculitic neuropathy may need a nerve biopsy if the diagnosis cannot be reached by other means. Nerve biopsy may also be helpful in patients with sarcoidosis, amyloidosis or a disabling neuropathy where the diagnosis has not been made despite extensive investigations.

Formal autonomic function tests may be helpful. Autonomic involvement is prominent in diabetic and amyloid neuropathies, rare inherited neuropathies and Guillain–Barré syndrome.

Peripheral neuropathies I clinical approach and investigations

Peripheral nerve damage is either axonal, demyelination or vascular, or a combination of these.

Neuropathies can present with distal symmetrical loss, asymmetrical loss, mononeuropathies and, rarely, mononeuritis multiplex.

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