Peripheral neuropathy

Introduction
Peripheral neuropathy is a disorder resulting from damage to the peripheral nerves, which carry sensory, motor, and autonomic signals between the central nervous system and the rest of the body. It can be caused by a wide range of systemic diseases, toxic exposures, nutritional deficiencies, infections, and inherited disorders. Clinical presentation varies depending on the type and distribution of nerves affected.

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Classification

1. By Nerve Type Involved

• Sensory neuropathy: Affects sensory fibers → numbness, tingling, pain.

• Motor neuropathy: Affects motor fibers → weakness, muscle atrophy.

• Autonomic neuropathy: Affects autonomic fibers → blood pressure instability, sweating abnormalities, GI/bladder dysfunction.

• Mixed sensorimotor neuropathy: Most common type.

2. By Distribution

• Mononeuropathy: Single nerve involvement (e.g., carpal tunnel syndrome).

• Mononeuritis multiplex: Multiple noncontiguous nerves affected.

• Polyneuropathy: Symmetrical involvement of multiple nerves, often starting distally (“glove and stocking” pattern).

3. By Pathology

• Axonal neuropathy: Damage to the axon.

• Demyelinating neuropathy: Damage to myelin sheath (e.g., Guillain–Barré syndrome, chronic inflammatory demyelinating polyneuropathy).

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Etiology

Metabolic and Endocrine

• Diabetes mellitus (most common cause worldwide).

• Hypothyroidism.

• Chronic kidney disease (uremic neuropathy).

Nutritional Deficiencies

• Vitamin B12, B1 (thiamine), B6, vitamin E deficiency.

Infectious

• HIV, Lyme disease, hepatitis C, leprosy.

Autoimmune and Inflammatory

• Guillain–Barré syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP), vasculitis.

Toxic

• Alcohol, heavy metals (lead, arsenic, mercury), certain chemotherapy drugs (cisplatin, vincristine), excessive vitamin B6.

Hereditary

• Charcot–Marie–Tooth disease and other inherited neuropathies.

Other

• Paraneoplastic syndromes, amyloidosis, sarcoidosis.

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Pathophysiology
Peripheral nerve damage results from direct injury to axons, demyelination, or both. Axonal degeneration leads to reduced nerve conduction amplitude, while demyelination slows conduction velocity. Chronic damage can cause secondary muscle atrophy and loss of reflexes.

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Clinical Features

Sensory symptoms:

• Numbness, tingling (“pins and needles”), burning pain.

• Allodynia (pain from non-painful stimuli).

• Loss of proprioception and vibration sense.

Motor symptoms:

• Weakness (distal more than proximal in polyneuropathy).

• Muscle wasting.

• Foot drop or wrist drop.

Autonomic symptoms:

• Orthostatic hypotension.

• Anhidrosis or hyperhidrosis.

• GI symptoms: Constipation, diarrhea, gastroparesis.

• Bladder dysfunction.

• Sexual dysfunction.

Pattern:

• Symmetrical distal (“stocking-glove”) distribution in most polyneuropathies.

• Asymmetrical or focal in mononeuropathies/mononeuritis multiplex.

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Investigations

Basic laboratory tests (guided by history and examination):

• Fasting glucose, HbA1c.

• Thyroid function tests.

• Serum vitamin B12 ± methylmalonic acid.

• Renal and liver function tests.

• ESR, CRP.

• Serum protein electrophoresis (for monoclonal gammopathy).

Specific tests:

• Autoantibody testing (ANA, ANCA) if autoimmune suspected.

• Infectious serology (HIV, hepatitis B/C, Lyme).

• Heavy metal screening if exposure suspected.

Electrodiagnostic studies:

• Nerve conduction studies and electromyography (NCS/EMG) to distinguish axonal vs demyelinating neuropathy and assess severity.

Other:

• Nerve biopsy in selected unclear cases.

• Genetic testing for suspected hereditary neuropathy.

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Management

1. Treat Underlying Cause

• Tight glycemic control in diabetes.

• Vitamin replacement (e.g., vitamin B12 1 mg IM daily for 1 week, weekly for 1 month, then monthly).

• Stop offending drugs/toxins.

• Treat infections (antibiotics for Lyme, antiretrovirals for HIV).

• Manage autoimmune causes with immunosuppressive therapy (corticosteroids, IV immunoglobulin, plasma exchange).

2. Symptomatic Treatment

Pain management (neuropathic pain agents):

• Amitriptyline: 10–75 mg orally at night.

• Duloxetine: 30–60 mg orally once daily.

• Pregabalin: 75–300 mg orally twice daily.

• Gabapentin: 300–1,200 mg orally three times daily.

• Topical capsaicin or lidocaine patches for focal pain.

Motor symptoms:

• Physical therapy to maintain muscle strength and prevent contractures.

• Orthotic devices for foot drop/wrist drop.

Autonomic symptoms:

• Orthostatic hypotension: Increased fluid and salt intake, compression stockings, midodrine (2.5–10 mg orally three times daily), or fludrocortisone (0.1–0.2 mg daily).

• GI symptoms: Dietary modifications, prokinetics (e.g., metoclopramide 10 mg before meals).

• Bladder dysfunction: Timed voiding, intermittent catheterization if needed.

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Prevention and Lifestyle Measures

• Control diabetes, hypertension, and other chronic diseases.

• Avoid excessive alcohol consumption.

• Balanced diet with adequate vitamins and minerals.

• Protective footwear to prevent injury in patients with sensory loss.

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Prognosis

• Depends on cause: Some neuropathies (e.g., due to B12 deficiency) are reversible with treatment; others (e.g., hereditary forms) are progressive.

• Early diagnosis and management can slow progression and improve quality of life.