6. Peripheral Neuropathy

MD, MSc, CMedEd, MACP, FRACP, FRCP-London · Senior Associate Dean, Collaboration for InterProfessional Health Education Research & Scholarship (CIPHERS)

Authors

Keely Coxon, MD
Dawn DeWitt, MD

In this module

Peripheral nerves

Role: Carry sensory and motor information between the brain/spinal cord (central nervous system (CNS)) and the rest of the body.
Each peripheral nerve is individually myelinated, produced by Schwann cells (vs. oligodendrocytes in CNS).

Types of peripheral nerves

Motor nerves*
Sensory nerves*
Autonomic nerves
Note

Signal movement of muscles under voluntary control. This includes skeletal muscle, which allows us to conduct everyday activities like walking, holding objects, and chewing.

Relay sensations of pain, temperature, and touch from the body back to the brain.

Control the involuntary actions of muscles and organs. The autonomic nervous system regulates breathing, digestion/GI motility, cardiac pacemaker cells, and certain glandular secretions.

*Some nerves are mixed, with both motor and sensory functions.

What is peripheral neuropathy?

Dysfunction of peripheral nerves, generally resulting from damage to the axon and/or myelin sheath.

Peripheral neuropathies are usually divided into two categories:

Examples

Guillain-Barré syndrome.
Chronic inflammatory.
Demyelinating polyneuropathy (CIDP).

Examples

Diabetic neuropathy.
Toxin exposure (including ETOH, drugs).

Common exam findings

Weakness.
Muscle atrophy.
Changes in sensation:
- Pain.
- Paresthesias.
- Loss of sensation.
Decreased or absent deep tendon reflexes (DTRs).

Principle causes of peripheral neuropathy

Autoimmunity (inflammatory demyelinative polyradiculoneuropathies).
Vasculitis (connective tissue diseases).
Systemic illness (diabetes, uremia, sarcoidosis, myxedema, acromegaly).
Cancer (paraneoplastic neuropathy).
Infections (diphtheria, leprosy, lyme disease, AIDS, herpes zoster).
Dysproteinemia (myeloma, cryoglobulinemia).
Nutritional deficiencies and alcoholism.
Compression and trauma.
Toxic industrial agents and drugs.
Inherited neuropathies.

Source: Pathological Patterns of Neuropathy.

Pathophysiology of peripheral neuropathy

It is useful to classify peripheral neuropathies as mononeuropathies (for example, carpal tunnel syndrom) or polyneuropathies (such as diabetic neuropathy).

Segmental demyelination
Wallerian degeneration
Axonal degeneration

Degeneration of myelin sheath; spares axon.
May present unilaterally or bilaterally (symmetric).
E.g., Guillain-Barre syndrome (axonal neuropathy in severe cases); Charcot-Marie-Tooth disease; MGUS-related neuropathy.

Focal mononeuropathy caused by direct trauma to nerve (e.g., compression, lesion, infarction); axon begins to degenerate distal to insult.

Most often these are length dependent (the signs and symptoms are most prominent in the lower extremities compared to the upper extremities).
- A.k.a. “dying back” phenomenon; begins distally and progresses in a proximal direction.
Generally presents as symmetric polyneuropathy with noticeable weakness.
E.g., diabetic polyneuropathy, HIV- and HCV-related neuropathy.

Note

Most common causes of adult-onset neuropathy in developed nations: Diabetes and alcoholism. Thirty to 40 percent of peripheral neuropathies are idiopathic, especially in older patients with mild symptoms.

Diagnostic studies in peripheral neuropathy

The AAN guideline says the highest-yield studies are fasting blood sugar, B12 level, and SPEP.

Electromyography (EMG)

Helps distinguish a primary muscle disorder (myopathy) from neuropathy.

Nerve conduction studies (NCS)

Helps distinguish axonal processes from demyelinating.
Axonal = decreased amplitude of action potential.
Demyelinating = slowed conduction velocity.

Nerve biopsy

Less-commonly done, but can help with definitive diagnosis.

Lumbar puncture

CSF can be useful in diagnosing certain neuropathies, especially inflammatory.

Labs

CBC: WBC [inflammation/infection], anemias.
CMP: metabolic derangements.
ANA.
CRP.
ESR.
TSH.
A1C.
B12.

Electromyography

An EMG involves inserting a thin needle electrode into a muscle . . .

A nerve conduction study (or nerve conduction velocity, “NCV,” test) involves measuring how fast a nerve impulse travels between electrodes.

Electrical activity of nerves is measured as: Sensory nerve action potential (SNAP) and Compound muscle action potential (CMAP) Axonal neuropathy has decreased amplitude Demyelination shows reduced conduction velocity.

Previous image

Next image

Axonal vs. demyelinating neuropathies

	Axonal Neuropathies	Demyelinating Neuropathies
Etiology	Trauma (including compression). Metabolic conditions. Drug and toxin exposure, especially industrial and agricultural chemicals.	Inflammatory examples Acute inflammatory demyelinating polyneuropathy (AIDP; Guillain-Barre syndrome is most common cause). Chronic inflammatory demyelinating polyneuropathy (CIDP) Hereditary example Charcot-Marie-Tooth disease (“hereditary motor sensory neuropathy [HMSN]”).
Pathophysiology	Direct insult to nerve axon results in degeneration distal to the site of injury (“Wallerian degeneration”). May also involve myelin sheath.	Myelin facilitates more rapid conduction of nerve impulses demyelinating processes block or slow normal conduction velocity.
Diagnosis	Labs may reveal metabolic derangement or evidence to support toxin exposure. NCS: Decreased amplitude of nerve action potential.	History Acute vs. chronic. Family history is important! Recent illness (esp due to Campylobacter jejuni) or vaccination Guillain Barre syndrome. Clinical course Inflammatory: Tends to present with “patchy” axonal damage. May see partial or full recovery over time (weeks/months). Hereditary: Tends to involve diffuse axonal damage, with slowly progressive course. EMG/NCS Slowed conduction velocity.
Management	Can often be treated by addressing the source of the axonal damage.	Chronic inflammatory neuropathies: May be able to treat using steroids, immunosuppressive medications, IVIG, and more. Guillain-Barre syndrome: Depending on severity, may consider IVIG.

Image credits

Unless otherwise noted, images are from Adobe Stock.