Peripheral Neuropathy

Question 1

Peripheral neuropathy

Answer 1

Peripheral neuropathy is a broad term that refers to any disorder of the peripheral nervous system.

Question 2

Peripheral neuropathies can be further divided into different forms depending on the type and pattern of nerve involvement. These include:

Answer 2

Polyneuropathy: refers to generalised involvement of multiple peripheral nerves
Radiculopathy: refers to involvement of a spinal nerve root
Plexopathy: refers to involvement of a network of nerves known as a plexus (e.g. brachial plexus)
Mononeuropathy: refers to involvement of a single nerve
Mononeuritis multiplex: refers to simultaneous or sequential involvement of ≥ 2 separate nerves

Question 3

We have grouped the major causes of peripheral neuropathy into the categories below (not an exhaustive list):

Answer 3

Idiopathic
Vascular: vasculitis
Metabolic: diabetes mellitus, hypothyroidism
Infective: HIV, Lyme disease, hepatitis C
Inflammatory: chronic inflammatory demyelinating polyneuropathy
Autoimmune: Guillain-Barré syndrome, connective tissue diseases
Neoplastic: paraneoplastic syndromes, multiple myeloma, tumours (causing compression)
Nutritional: Vitamin B12 or folate deficiency
Drugs: chemotherapy, Isoniazid, Metronidazole
Systemic illness: critical illness, chronic kidney disease, chronic liver disease, amyloidosis
Toxic: heavy metals, alcohol
Trauma: usually due to compression
Hereditary: Charcot-Marie tooth, familial amyloidosis

Question 4

Regardless of the underlying aetiology, damage to peripheral nerves is caused by three major mechanisms:

Answer 4

Axonal degeneration: damage to nerve axons. Typically causes a ‘dying-back phenomenon’ that starts distal and progresses proximally. Usually causes symmetrical polyneuropathy with weakness
Wallerian degeneration: damage to the nerve axon due to a lesion or physical compression (e.g. carpal tunnel syndrome). Commonly seen in mononeuropathies with the portion of the nerve distal to the compression affected
Demyelination: degeneration of the myelin sheath is seen. In pure demyelination, there is sparing of the axon. The clinical presentation is more variable

Question 5

Polyneuropathies

Answer 5

Polyneuropathies often are often ‘length-dependent’ meaning more distal nerves are affected first.

Question 6

Answer 6

Polyneuropathy with ‘glove and stocking’ distribution

Question 7

There are many different causes of polyneuropathy and the onset and disease course largely depends on the aetiology. For example, … polyneuropathy often starts as a slowly progressive sensory/painful polyneuropathy. On the other hand, … can cause an acute, rapidly progressive polyneuropathy with predominant weakness.

Answer 7

There are many different causes of polyneuropathy and the onset and disease course largely depends on the aetiology. For example, diabetic polyneuropathy often starts as a slowly progressive sensory/painful polyneuropathy. On the other hand, Guillain-Barré syndrome can cause an acute, rapidly progressive polyneuropathy with predominant weakness.

Question 8

…: a collection of muscles innervated by a single spinal nerve root
…: an area of skin supplied by a single spinal nerve root

Answer 8

Myotome: a collection of muscles innervated by a single spinal nerve root
Dermatome: an area of skin supplied by a single spinal nerve root

Question 9

Sciatica is a non-specific clinical description of pain affecting the back and/or leg.

Answer 9

It is typically used to describe a sharp or burning pain that radiates from the buttock along the course of the sciatic nerve down the posterior/lateral leg and usually to the foot or ankle. The sciatic nerve is formed by a combination of nerve roots L4, L5, S1, S2, and S3. Therefore, the involvement of any of these nerve roots alone or in combination can cause a variety of sciatic-like symptoms.

Sciatica is therefore the clinical manifestation of lumbosacral radiculopathies. However, the difficulty arises in the fact that the term is used more generally as a reference to lower back pain that may be non-radicular in origin (i.e. not caused by radiculopathy). Therefore, when a patient has ‘sciatica’ it is important to determine exactly what is meant by the term and whether there is ‘radicular’ quality to the pain.

Question 10

A mononeuropathy refers to damage or dysfunction of a single peripheral nerve.

Answer 10

Mononeuropathy is a broad term that refers to damage or dysfunction of a single peripheral nerve. This typically leads to a characteristic set of clinical features with motor and/or sensory dysfunction relating to the usual function of the nerve involved.

Mononeuropathies are commonly due to entrapment or compression as peripheral nerves have to travel through small openings and between other major structures. Compression of the nerve may be internal (e.g. nerve tumour), or external (e.g. fracture, compressive clothing, unusual posture).

Question 11

There are many peripheral nerves in the body and each may be affected in different ways as the course of each nerve is different. We can broadly think of mononeuropathies in three groups:

Answer 11

Cranial mononeuropathies: relates to the 12 paired nerves arising from the brain and brainstem
Upper limb mononeuropathies: relates to the peripheral nerves involved in upper limb function
Lower limb mononeuropathies: relates to the peripheral nerves involved in lower limb function

Question 12

A plexus refers to a collection of proximal segments of peripheral nerves.

Answer 12

When spinal nerve roots exit the spinal cord they may enter a plexus. A plexus simply refers to a branching network of nerves (or vessels). They may arise from the merging of spinal nerves (e.g. cervical plexus, lumbosacral plexus) or the merging of autonomic nerves around major organs (e.g. cardiac plexus, coeliac plexus).

With spinal nerve plexuses, they are formed by a merging and intertwining of proximal segments of peripheral nerves before they form individual nerves more distally. This means that information from multiple spinal nerve roots may be conveyed along a single peripheral nerve.

The two major plexuses are the brachial and lumbosacral. When there is damage or dysfunction of a plexus it is known as a plexopathy.

Question 13

Brachial plexus

This is formed by the nerve roots C5-T1. It is divided into different regions known as trunks, divisions, cords, and terminal branches. There are different causes of brachial plexopathy that may be broadly divided into traumatic and non-traumatic. The clinical presentation depends on the pattern of involvement of the brachial plexus:

Answer 13

Traumatic: contact sport, difficult birth (e.g. Erbs’ palsy with the arm held in Waiter’s tip position), road traffic accident
Non-traumatic: neuralgic amyotrophy (an inflammatory disorder of brachial plexus), other rare causes (e.g. thoracic outlet syndrome)

Question 14

Lumbosacral plexus

Answer 14

The lumbosacral plexus is formed by the nerve roots L1-S4. Each root divides into anterior and posterior branches that subsequently merge and intertwine to form individual nerves. Damage to the lumbosacral plexus is commonly due to trauma and leads to a constellation of symptoms including asymmetrical weakness, numbness, and paraesthesia in the distribution of multiple lumbosacral nerve roots.

Question 15

Mononeuritis multiplex

Answer 15

Mononeuritis multiplex refers to simultaneous or sequential involvement of ≥2 separate nerves.

Question 16

What are key investigations to confirm peripheral neuropathy?

Answer 16

Electromyography and nerve conduction studies are key investigations to confirm peripheral neuropathy.

Question 17

Electrodiagnostic tests

Electrodiagnostic tests can be used to confirm peripheral neuropathy and these should be requested and interpreted in line with the clinical presentation. The two main tests include electromyography (EMG) and nerve conduction studies (NCS):

Answer 17

Electromyography (evaluates muscle units): this refers to an assessment of the electrical activity of muscles. It can assess activity during rest and voluntary contraction. It is important in the assessment and diagnosis of neuromuscular disease. It helps to differentiate between the different types of peripheral neuropathy (e.g. motor mononeuropathies, plexopathy) as well as muscle abnormalities (e.g. neuromuscular junction, myopathy). EMG records the electrical potentials generated in a muscle belly through the insertion of a needle
Nerve conduction studies (evaluates peripheral nerves): this refers to an assessment of individual peripheral nerve function. It essentially involves activating nerves electrically over several points on the skin of the upper/lower limbs and measuring the response. The test involves assessing both the size (i.e. amplitude) and speed (i.e. velocity) of signals through the motor and sensory fibres. These studies can determine the type of injury (e.g. demyelinating, axonal degeneration or conduction block from compression).

Question 18

A wide number of investigations can be requested to determine the cause of peripheral neuropathy. The choice of test largely depends on the type of peripheral neuropathy, clinical presentation and pattern of involvement.

Answer 18

Full blood count: may show macrocytic anaemia suggestive of vitamin B12 or folate deficiency. Macrocytosis may also be a feature of some haematological malignancies and alcohol excess
Renal function: assess for chronic kidney disease
HbA1c: assess for diabetes mellitus
Thyroid function tests: assess for hypothyroidism
Immunological: immunoglobulins and protein electrophoresis for plasma cell disorders (e.g. myeloma)
Autoimmune tests: ANA, ENA, Anti-CCP, complement for connective tissue diseases
Virology/Infection: serology for hepatitis C, syphilis, or Lyme disease
Heavy metals: copper, lead
Vitamins: B12, folate, pyridoxine
Imaging: MRI, CT or US may be needed if there is concern about compression or structural lesions
Biopsy: a nerve biopsy may be rarely performed
Genetic testing: specialist test that may be considered for hereditary causes

Question 19

It is important to also consider the symptoms of the patient who may be experiencing painful paraesthesia and/or motor weakness. These patients may require neuropathic pain medications to reduce the severity of the symptoms (e.g. Gabapentin, …) and may require additional help from allied health professionals (e.g. physiotherapy and occupational therapy if disabling foot drop).

Answer 19

It is important to also consider the symptoms of the patient who may be experiencing painful paraesthesia and/or motor weakness. These patients may require neuropathic pain medications to reduce the severity of the symptoms (e.g. Gabapentin, duloxetine) and may require additional help from allied health professionals (e.g. physiotherapy and occupational therapy if disabling foot drop).