What is neuropathy?

What is Neuropathy?

Neuropathy is damage to peripheral nerves that causes symptoms ranging from numbness and tingling to severe pain, weakness, and autonomic dysfunction, affecting approximately 1% of adults worldwide with prevalence increasing to 7% in those over 65 years. 1, 2

Core Definition and Pathophysiology

Neuropathy refers to damage affecting the peripheral nervous system, which includes all nerves outside the brain and spinal cord. 1 The condition encompasses:

• Sensory symptoms: Pain, tingling, numbness, or "pins-and-needles" sensations, with inability to feel hot/cold or pain 3
• Motor symptoms: Muscle weakness, balance problems, twitching, cramping, muscle wasting, or difficulties with swallowing and breathing 3
• Autonomic symptoms: Dizziness, faintness, digestive problems, sexual dysfunction, sweating abnormalities, and urination difficulties 3

Clinical Presentation Patterns

Distribution and Progression

Neuropathy is typically length-dependent and symmetric, meaning symptoms begin in the longest nerve axons (toes) and progress proximally over time, affecting sensory axons more than motor axons. 1

• Symptoms characteristically start distally in the feet and may progress up the limbs 3
• Asymmetrical symptoms should prompt investigation for other etiologies, as peripheral neuropathy is invariably symmetrical 4
• Up to 50% of cases may be asymptomatic, placing patients at risk for injuries and foot ulcers if preventive care is not implemented 3

Neuropathic Pain Characteristics

When pain is present, it has distinctive features:

• Burning pain, "electrical shock" sensations, stabbing or knife-like pains, and uncomfortable tingling affect up to 50% of patients 4
• Allodynia (pain from normally non-painful stimuli like clothing touching skin) is common 4
• Patients describe walking as "barefoot on marbles" or "barefoot on hot sand" 4
• Pain is characteristically more severe at night, causing sleep disturbance 4
• Altered temperature perceptions occur, with feet feeling abnormally warm or cold 4

Common Causes

Diabetes is the most common cause of neuropathy, affecting approximately 206 million people worldwide and accounting for more than 50% of peripheral neuropathy in Western populations. 1

Other major causes include:

• Idiopathic: 20-27% of cases have no identifiable cause after diagnostic testing 1, 2
• Toxic/medication-induced: Chemotherapy agents (cisplatin, paclitaxel, vincristine), amiodarone, HIV medications, alcohol 1, 5
• Nutritional deficiencies: Particularly vitamin B12 1
• Hereditary conditions: Charcot-Marie-Tooth disease 1, 5
• Monoclonal gammopathies 1
• Nerve compression: Carpal tunnel syndrome (most common mononeuropathy, affecting 5% of population) 2

Clinical Impact

The burden of neuropathy extends beyond physical symptoms:

• Neuropathic pain significantly impacts quality of life, causing severe sleep disturbance, fatigue, and reduced daily activities 4
• Over two-thirds of patients with painful diabetic neuropathy experience anxiety and/or depression 4
• The impact on quality of life, mood, and sleep exceeds the burden of the causative pathology 6

Diagnostic Approach

Initial Screening

For diabetic patients specifically:

• Assessment should begin at diagnosis of type 2 diabetes and 5 years after diagnosis of type 1 diabetes, with annual re-evaluation thereafter 3
• Neurologic testing should include temperature sensation, pinprick sensation (small-fiber function), vibration perception using 128-Hz tuning fork (large-fiber function), pressure sensation, and ankle reflexes 3
• Annual 10-g monofilament testing identifies feet at risk for ulceration and amputation 3

Key Diagnostic Considerations

Neuropathy is a diagnosis of exclusion—nondiabetic neuropathies may be present in people with diabetes and may be treatable. 3

Conditions to exclude include:

• Cervical and lumbar disease (nerve root compression, spinal stenosis) 3
• Cerebral infarction 3
• Guillain-Barré syndrome 3
• Severe arteriovenous disease 3
• Drug neurotoxicity 3
• Metabolic toxicants from renal insufficiency 3

Recommended Initial Laboratory Testing

• Fasting blood glucose (for diabetes) 1, 7
• Serum B12 with metabolites (methylmalonic acid with or without homocysteine) 1, 7
• Serum protein electrophoresis with immunofixation (for monoclonal gammopathies) 1, 7
• Complete blood count and comprehensive metabolic profile 7
• Thyroid-stimulating hormone 7

Prognosis

The prognosis depends on the underlying cause, but complete reversal of nerve damage is uncommon even when treatments are available. 1 Glycemic control can effectively prevent diabetic peripheral neuropathy in type 1 diabetes and may modestly slow progression in type 2 diabetes, but does not reverse neuronal loss. 3