Key Facts

Peripheral neuropathy is extremely common. Systematic approach to classification (fibre type, distribution, pathology, tempo) narrows the differential efficiently. NCS/EMG is essential for distinguishing axonal from demyelinating neuropathy.

Epidemiology

Prevalence ~2-3% (up to 8% in over-55s). Diabetic neuropathy affects ~50% of diabetic patients. Alcohol-related neuropathy in ~10% of chronic alcoholics. ~25% remain idiopathic despite investigation (chronic idiopathic axonal polyneuropathy — CIAP).

Aetiology

Common causes by pattern:

• Distal symmetric polyneuropathy (commonest): diabetes (most common overall), alcohol, B12 deficiency, drugs (chemotherapy — cisplatin, vincristine, taxanes; isoniazid; amiodarone; metformin-induced B12 deficiency), chronic kidney disease, hypothyroidism
• Mononeuritis multiplex: vasculitis (PAN, GPA, EGPA), diabetes, sarcoidosis, leprosy, amyloidosis, paraneoplastic
• Demyelinating neuropathy: CIDP, GBS, CMT (hereditary), anti-MAG paraprotein
• Small fibre neuropathy: diabetes, amyloidosis, Fabry disease, sarcoidosis (NCS may be normal)

Pathophysiology

Axonal degeneration: damage to the axon itself (dying-back pattern — distal to proximal); NCS shows reduced CMAP/SNAP amplitudes with preserved conduction velocities. Causes: metabolic, toxic, nutritional. Demyelination: damage to the myelin sheath; NCS shows reduced conduction velocities, prolonged distal latencies, conduction block. Causes: immune-mediated (CIDP, GBS), hereditary (CMT).

Sensory Neuropathy

• Large-fibre loss: numbness, tingling, loss of vibration/proprioception, sensory ataxia (positive Romberg), absent ankle jerks
• Small-fibre loss: burning pain, dysaesthesia, reduced pain/temperature sensation; autonomic features; NCS may be NORMAL

Motor Neuropathy

• Distal weakness: foot drop (common peroneal), wrist drop (radial), hand weakness
• Muscle wasting, fasciculations (if LMN affected)

Autonomic Neuropathy

• Postural hypotension, resting tachycardia, gustatory sweating, erectile dysfunction, gastroparesis, constipation/diarrhoea, bladder dysfunction

Key Patterns

• Glove-and-stocking: length-dependent; diabetes, alcohol, B12
• Mononeuritis multiplex: painful, asymmetric, multiple named nerves; vasculitis
• Proximal + distal weakness: CIDP, GBS

Red Flags

• Rapidly progressive weakness → GBS
• Mononeuritis multiplex → vasculitis (urgent investigation)
• Weight loss + neuropathy → malignancy, amyloidosis
• Young patient with neuropathy → hereditary (CMT), Fabry disease
• Predominant motor neuropathy → think CIDP, multifocal motor neuropathy

Bedside

• Neurological examination: sensory modalities (light touch, pinprick, vibration, proprioception), power, reflexes, gait (Romberg)
• Monofilament testing: 10g monofilament for diabetic foot screening

Bloods (First-Line)

• HbA1c / fasting glucose: diabetes
• FBC: macrocytosis (B12, alcohol)
• B12 and folate: deficiency
• TFTs: hypothyroidism
• U&Es: renal failure
• LFTs and GGT: alcohol
• SPEP + immunofixation: paraprotein
• ESR/CRP: vasculitis, infection

Bloods (Second-Line — Guided by Clinical Suspicion)

• ANCA, ANA, dsDNA, complement: vasculitis
• HIV, hepatitis B/C: infectious causes
• Anti-neuronal antibodies: paraneoplastic
• Serum ACE: sarcoidosis
• Urine Bence Jones: myeloma
• Alpha-galactosidase A: Fabry disease (young patients)

Neurophysiology

• NCS/EMG: essential; distinguishes axonal from demyelinating; identifies mononeuritis multiplex pattern; guides further investigation

Special Tests

• Nerve biopsy (sural): vasculitis, amyloidosis, sarcoidosis; rarely needed
• Skin biopsy: intraepidermal nerve fibre density — gold standard for small fibre neuropathy
• Genetic testing: CMT (PMP22 duplication for CMT1A)
• Lumbar puncture: if CIDP/GBS suspected

Treat Underlying Cause

• Diabetes: optimise glycaemic control (NICE NG28)
• B12 deficiency: hydroxocobalamin 1 mg IM on alternate days × 2 weeks, then every 2-3 months
• Alcohol: abstinence, thiamine supplementation (Pabrinex IV initially, then oral thiamine 100 mg TDS)
• Drug-induced: stop or reduce offending agent
• CIDP: immunotherapy (see CIDP section)
• Vasculitis: immunosuppression (steroids ± cyclophosphamide)

Neuropathic Pain Management (NICE CG173)

• First-line: amitriptyline 10-75 mg ON, duloxetine 60-120 mg OD, gabapentin 300-3600 mg/day, or pregabalin 150-600 mg/day
• Second-line: combination of above; tramadol for acute rescue
• Topical: capsaicin 0.075% cream, lidocaine 5% plasters (localised neuropathic pain)
• Specialist: referral to pain clinic for refractory neuropathic pain

Rehabilitation

• Physiotherapy: gait training, balance, falls prevention
• Orthotics: ankle-foot orthoses for foot drop
• Occupational therapy: adaptive devices

Referral Criteria

• Neurology: diagnostic uncertainty, suspected CIDP/vasculitis, atypical features, progressive motor neuropathy
• Rapidly progressive or mononeuritis multiplex: urgent referral

Depends on cause. Diabetic neuropathy: progressive if glycaemic control poor; pain may improve with good control. B12 deficiency: partially reversible if treated early (neurological damage may be permanent if delayed). CIDP: ~80% respond to treatment. Idiopathic neuropathy (CIAP): generally slowly progressive, minimal disability. Vasculitic neuropathy: prognosis depends on underlying disease and treatment response.

Axonal vs Demyelinating Neuropathy

Causes of Mononeuritis Multiplex (Exam Favourite)