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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Most common pattern: distal symmetric sensorimotor polyneuropathy with "glove-and-stocking" sensory loss
- Two most common causes in the UK: diabetes (~30%) and alcohol (~10%). Together ~40–50% of cases
- Investigate with nerve conduction studies (NCS), bloods (glucose/HbA1c, B12, TFTs, protein electrophoresis)
- Neuropathic pain: amitriptyline, duloxetine, gabapentin, or pregabalin first-line (NICE CG173)
- Treat underlying cause where possible: glycaemic control, alcohol cessation, B12 replacement
Overview
Peripheral neuropathy refers to damage or dysfunction of one or more peripheral nerves. It is classified by distribution (mononeuropathy, mononeuritis multiplex, polyneuropathy), pathology (axonal or demyelinating), fibre type (sensory, motor, autonomic, or mixed), and aetiology. The most common pattern is a chronic distal symmetric sensorimotor polyneuropathy, typically axonal, presenting with glove-and-stocking sensory loss starting in the feet. Diabetes mellitus is the most common cause worldwide. Other important causes include alcohol, B12 deficiency, chronic kidney disease, hypothyroidism, drugs (chemotherapy, amiodarone), and paraproteinaemias.
Epidemiology
Peripheral neuropathy affects approximately 2–8% of the general population, rising to ~50% of people with diabetes. It is more common with increasing age. In up to 25% of cases, no cause is identified (cryptogenic/idiopathic neuropathy). Hereditary neuropathies (Charcot-Marie-Tooth disease) affect approximately 1 in 2,500.
Clinical Features
Symptoms
Numbness and tingling in feet and hands (glove-and-stocking distribution)
Burning, shooting, or electric-shock pain (neuropathic pain)
Loss of balance — proprioceptive loss causes sensory ataxia
Weakness — distal > proximal (foot drop in peroneal neuropathy, wrist drop in radial neuropathy)
Autonomic symptoms: postural hypotension, erectile dysfunction, gastroparesis, bladder dysfunction (diabetic autonomic neuropathy)
Painless injuries and foot ulcers (loss of protective sensation — diabetic foot)
Signs
Reduced sensation distally: loss of vibration sense (first to go), light touch, pinprick, proprioception
Absent ankle jerks (early sign)
Distal muscle wasting (intrinsic foot muscles, small muscles of hands)
High-stepping gait (foot drop)
Charcot joint: painless deformed joint with neuropathic arthropathy (especially diabetic)
Positive Romberg test (proprioceptive loss)
Investigations
First-line
BloodsHbA1c/fasting glucose (diabetes), B12, folate, TFTs, U&Es (CKD), LFTs (alcohol), serum protein electrophoresis (paraprotein), FBC, ESR/CRP
Nerve conduction studies (NCS) and EMGConfirms neuropathy, classifies as axonal (reduced amplitudes) or demyelinating (reduced velocities, conduction block), and distribution
Second-line
Urine Bence Jones proteinIf paraprotein detected — screen for myeloma
Anti-neuronal antibodiesAnti-MAG, anti-GM1 (multifocal motor neuropathy), anti-ganglioside panel
HIV test, syphilis serologyIf risk factors present
Specialist
Nerve biopsy (sural nerve)Rarely needed — for vasculitic neuropathy, amyloidosis, or diagnostically uncertain cases
Genetic testingPMP22 duplication (CMT1A) — most common form of Charcot-Marie-Tooth disease
Management
NICE CG173 (Neuropathic pain), 2013/20201
Treat underlying cause
- Diabetes: optimise glycaemic control (slows progression but rarely reverses established neuropathy)
- Alcohol: cessation + thiamine supplementation
- B12 deficiency: IM hydroxocobalamin replacement
- Hypothyroidism: levothyroxine
- Drug-induced: withdraw causative agent if possible
2
Neuropathic pain management (NICE CG173)
- First-line (choose one): amitriptyline 10–75 mg at night, duloxetine 60–120 mg/day, gabapentin 300–3600 mg/day, or pregabalin 150–600 mg/day
- If first-line fails: switch to another first-line agent. If partial response: consider combination
- Tramadol: short-term rescue only — not for long-term use
- Capsaicin cream 0.075%: for localised neuropathic pain
- Specialist referral if pain refractory to two first-line agents
3
Foot care (diabetic neuropathy)
- Annual foot examination: monofilament testing, pulse palpation
- Patient education: daily foot inspection, appropriate footwear, avoid walking barefoot
- Prompt treatment of foot ulcers — MDT diabetic foot clinic
Complications
- Falls and injuries: Proprioceptive loss and motor weakness — fall risk assessment
- Diabetic foot ulcers: Loss of protective sensation → unnoticed injuries → infection → amputation
- Charcot neuroarthropathy: Painless progressive joint destruction — especially midfoot in diabetes
- Chronic pain: Neuropathic pain can be severe and refractory — significant impact on quality of life
- Autonomic neuropathy: Postural hypotension (falls), gastroparesis, silent MI, erectile dysfunction
UKMLA Exam Tips
- 1Glove-and-stocking sensory loss + absent ankle jerks = distal symmetric polyneuropathy — check glucose and B12
- 2Diabetes and alcohol together account for ~40–50% of all peripheral neuropathy
- 3Vibration sense (dorsal column) is typically lost first in peripheral neuropathy
- 4Neuropathic pain treatment (NICE CG173): amitriptyline, duloxetine, gabapentin, or pregabalin — all first-line choices
- 5Mononeuritis multiplex (multiple individual nerves affected): think vasculitis, diabetes, sarcoidosis, leprosy
- 6Charcot-Marie-Tooth: pes cavus, distal wasting ("inverted champagne bottle legs"), autosomal dominant
- 7Acute symmetric ascending weakness + areflexia = GBS (not chronic polyneuropathy)
practicetest your knowledge on peripheral neuropathyApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — neurology and beyond.
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Peripheral Neuropathy: guidance by region
Recommendations, thresholds and pathways can differ. Open the page written for the jurisdiction you need.