Peripheral Neuropathy

📋 Key Information Summary

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Peripheral neuropathy affects approximately 2–8% of the Australian adult population; diabetic sensorimotor polyneuropathy is the most common cause encountered in primary care.
Classify neuropathy by distribution (length-dependent vs multifocal vs focal), fibre type (motor, sensory, autonomic), tempo (acute, subacute, chronic), and pattern (axonal vs demyelinating) to guide investigations and management.
Red flags requiring urgent referral: rapidly progressive weakness over days to weeks (suspect GBS), respiratory compromise, asymmetric motor involvement, autonomic instability, or suspected vasculitic neuropathy.
Initial workup should include HbA1c/fasting glucose, serum B12 and folate, serum protein electrophoresis (SPEP), thyroid function, renal function (eGFR), full blood count, liver function tests, and autoimmune screening (ANA, anti-MAG, ANCA where indicated).
Nerve conduction studies (NCS) and electromyography (EMG) are the gold standard for confirming peripheral neuropathy, distinguishing axonal from demyelinating patterns, and identifying focal compressive lesions (MBS item 11005).
First-line analgesics for painful diabetic neuropathy are gabapentinoids (pregabalin, gabapentin) and SNRIs (duloxetine); both are PBS-listed for this indication in Australia.
Tricyclic antidepressants (amitriptyline, nortriptyline) are effective second-line agents but carry significant anticholinergic burden — use with caution in patients aged >65 years and those with cardiac conduction abnormalities.
Topical capsaicin 8% patch (Qutenza®) and lignocaine 5% patches are useful adjuncts for localised neuropathic pain; capsaicin requires PBS Authority approval for refractory cases.
Carpal tunnel syndrome is the most common mononeuropathy; confirm with NCS/EMG before surgical referral. Conservative measures (splinting, ergonomic modification) should be trialled for at least 6–8 weeks before considering carpal tunnel release.
Always screen for treatable aetiologies — particularly diabetes, B12 deficiency, hypothyroidism, and alcohol-related neuropathy — before attributing neuropathy to idiopathic causes.
Assess for fall risk, foot ulceration, and autonomic symptoms (orthostatic hypotension, gastroparesis, erectile dysfunction) as these significantly affect morbidity in chronic peripheral neuropathy.
Aboriginal and Torres Strait Islander Australians have higher rates of diabetes-related neuropathy; culturally safe foot care programmes and early screening are essential to reduce amputation rates.

Introduction & Australian Epidemiology

Peripheral neuropathy refers to damage or dysfunction of one or more peripheral nerves, producing sensory, motor, and/or autonomic symptoms. It represents one of the most common neurological presentations in Australian primary care and is a leading cause of morbidity, falls, foot ulceration, and impaired quality of life.

The prevalence of peripheral neuropathy in the general Australian population is estimated at 2–8%, rising sharply with age and the presence of diabetes mellitus. Diabetic peripheral neuropathy (DPN) affects up to 50% of individuals with type 2 diabetes during their lifetime, making it the most common cause in Australia. The Australian Institute of Health and Welfare (AIHW) reports that diabetes-related peripheral complications, including neuropathy, contribute significantly to the burden of preventable hospitalisations and lower-limb amputations, particularly among Aboriginal and Torres Strait Islander peoples.

Other common aetiologies encountered in Australian practice include chronic alcohol-related neuropathy, vitamin B12 deficiency (particularly in older adults and those on long-term metformin or proton pump inhibitors), chemotherapy-induced peripheral neuropathy (CIPN), chronic inflammatory demyelinating polyneuropathy (CIDP), and hereditary neuropathies such as Charcot–Marie–Tooth disease.

Early recognition, appropriate classification, and identification of reversible causes are the cornerstones of effective management. This guideline provides a structured approach to evaluation, investigation, and evidence-based management of peripheral neuropathy within the Australian healthcare context.

Aetiology	Estimated Prevalence	Key Australian Context
Diabetes mellitus (type 1 & 2)	Up to 50% of people with diabetes	Most common cause; ~1.3 million Australians with diagnosed diabetes (NDSS 2023)
Chronic alcohol use	Up to 65% with heavy use	Often co-exists with nutritional deficiency
Vitamin B12 deficiency	5–15% of adults >65 years	Risk increased with metformin and PPI use
Chemotherapy-induced (CIPN)	30–70% depending on agent	Platinum agents, taxanes, vinca alkaloids most implicated
Chronic inflammatory demyelinating polyneuropathy (CIDP)	1–9 per 100,000	Treatable — IVIg PBS-listed for CIDP
Charcot–Marie–Tooth disease	~1 in 2,500	Most common inherited neuropathy; genetic testing available
Idiopathic	Up to 25–30% of cases	Diagnosis of exclusion after comprehensive workup

Evaluation & Classification

A systematic approach to classifying peripheral neuropathy is essential for narrowing the differential diagnosis and guiding investigations. Classification should address four domains: distribution, fibre type involvement, tempo, and underlying pathophysiology.

Distribution Pattern

Pattern	Description	Common Causes
Length-dependent (distal symmetric)	Symptoms begin in the feet and progress proximally in a "stocking-glove" distribution; hands involved once symptoms reach mid-calf level	Diabetes, alcohol, B12 deficiency, idiopathic, CIPN
Multifocal (mononeuritis multiplex)	Asymmetric involvement of individual peripheral nerves, often at separate anatomical sites; may become confluent over time	Vasculitis (e.g. PAN, EGPA), sarcoidosis, diabetes, HIV, leprosy
Focal (single nerve)	Isolated involvement of a single nerve with clear anatomical localisation	Compression (CTS, ulnar, peroneal), trauma, nerve infarction
Proximal and distal (generalised)	Diffuse involvement from outset with prominent proximal weakness	GBS, CIDP, paraneoplastic, critical illness polyneuropathy

Fibre Type Involvement

Large-fibre sensory: Vibration and proprioception loss, sensory ataxia, reduced reflexes, positive Romberg sign. Patients report numbness, unsteadiness, and difficulty with fine motor tasks.
Small-fibre sensory: Burning pain, tingling, allodynia, and temperature sensation loss with preserved reflexes and normal NCS. Diagnosed clinically or with skin punch biopsy (intraepidermal nerve fibre density). Small-fibre neuropathy is increasingly recognised as a cause of burning feet with "normal" nerve conduction studies.
Motor: Weakness, cramping, fasciculations, muscle wasting, and reduced or absent reflexes. Suggests anterior horn cell, motor root, plexus, or motor-predominant nerve pathology.
Autonomic: Orthostatic hypotension, gastroparesis, bladder dysfunction, erectile dysfunction, gustatory sweating, resting tachycardia. Consider diabetic autonomic neuropathy, amyloidosis, or autoimmune autonomic ganglionopathy.

Tempo of Onset

Acute (days to <4 weeks): Guillain–Barré syndrome (GBS), vasculitis, toxins, porphyria, diphtheria. Requires urgent hospital assessment.
Subacute (4–8 weeks): CIDP, paraneoplastic, nutritional deficiency, toxic exposures, vasculitis.
Chronic (>8 weeks): Diabetic neuropathy, hereditary neuropathies, chronic alcohol use, idiopathic. Most common pattern in general practice.

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Red Flags — Urgent Referral Required:

Rapidly progressive ascending weakness over hours to days (suspect GBS) — admit acutely for respiratory monitoring and IVIg
Respiratory compromise (forced vital capacity <20 mL/kg or declining FVC) — ICU transfer
Asymmetric motor involvement with pain (suspect vasculitis or mononeuritis multiplex)
Autonomic instability: labile blood pressure, cardiac arrhythmias, urinary retention
Prominent proximal weakness with areflexia (suspect GBS, CIDP, or critical illness polyneuropathy)
New-onset neuropathy in a patient with known malignancy (suspect paraneoplastic)
Saddle anaesthesia with bladder/bowel dysfunction (consider cauda equina — not peripheral neuropathy, but an important differential)

Pathophysiology: Axonal vs Demyelinating

Feature	Axonal	Demyelinating
NCS pattern	Reduced amplitudes, normal/mildly slowed conduction velocities	Markedly slowed conduction velocities, prolonged distal motor latencies, conduction block, temporal dispersion
Common causes	Diabetes, alcohol, B12 deficiency, toxins	GBS (AIDP), CIDP, anti-MAG neuropathy, CMT1
Prognosis	Slow recovery (months to years); may be irreversible	Often treatable with immunotherapy; good prognosis if identified early
Key investigation	NCS/EMG, skin biopsy (small fibre)	NCS/EMG, CSF (elevated protein in GBS/CIDP), nerve biopsy rarely needed

Initial Laboratory Workup

A structured tiered approach to investigation ensures that common, treatable causes are identified efficiently before progressing to specialist testing.

Tier 1 — First-Line Investigations (All Patients)

These tests should be ordered for every patient presenting with suspected peripheral neuropathy in primary care:

Essential

HbA1c and fasting glucose

Diabetes is the most common cause; HbA1c ≥6.5% (48 mmol/mol) diagnostic. Consider oral glucose tolerance test (OGTT) if HbA1c borderline (5.7–6.4%) — up to 10% of DPN patients have isolated impaired glucose tolerance.

Essential

Serum vitamin B12 and folate

B12 deficiency causes subacute combined degeneration. Check methylmalonic acid (MMA) and homocysteine if B12 is borderline (150–250 pmol/L). Risk factors: metformin use >4 years, PPI use >1 year, vegan/strict vegetarian diet, pernicious anaemia, age >65 years.

Essential

Serum protein electrophoresis (SPEP) with immunofixation

Screen for monoclonal gammopathy, multiple myeloma, Waldenström macroglobulinaemia, POEMS syndrome, and AL amyloidosis. Anti-MAG antibodies should be ordered if IgM paraprotein is detected.

Essential

Thyroid function tests (TSH, fT4)

Hypothyroidism causes a mild axonal sensorimotor neuropathy; reversible with treatment. Hyperthyroidism may cause a rare thyrotoxic neuropathy.

Essential

Renal function (eGFR, creatinine, urea, electrolytes)

Chronic kidney disease causes uraemic neuropathy. eGFR also guides medication dosing adjustments (gabapentin, pregabalin). Refer for nephrology input if eGFR <30 mL/min/1.73 m².

Essential

Full blood count (FBC)

Macrocytosis suggests B12/folate deficiency or alcohol use. Pancytopaenia may indicate B12 deficiency or marrow infiltration.

Essential

Liver function tests (LFTs)

Elevated GGT supports chronic alcohol use. Transaminases and albumin assess hepatic function for medication dose adjustment and nutritional status.

Tier 2 — Second-Line Investigations (Directed by Clinical Suspicion)

Available

Antinuclear antibody (ANA), extractable nuclear antigens (ENA)

Consider in suspected autoimmune connective tissue disease (SLE, Sjögren syndrome). Sjögren syndrome causes a sensory ganglionopathy or sensorimotor neuropathy.

Available

ANCA (p-ANCA, c-ANCA)

Suspect vasculitis with mononeuritis multiplex, constitutional symptoms, elevated ESR/CRP. Microscopic polyangiitis and EGPA most commonly associated with peripheral neuropathy.

Available

HIV serology, hepatitis B & C serology

HIV causes distal symmetric polyneuropathy and GBS; hepatitis C associated with cryoglobulinaemic vasculitis and mononeuritis multiplex.

Available

Anti-ganglioside antibodies (anti-GM1, anti-GQ1b)

GBS subtyping: anti-GM1 in AMAN variant, anti-GQ1b in Miller Fisher syndrome. Request through specialist.

Available

Serum copper, caeruloplasmin, zinc

Copper deficiency (may mimic B12 deficiency), zinc toxicity. Check if history of gastric surgery, excessive zinc supplementation, or denture cream use.

Available

Gluten coeliac serology (anti-tTG IgA)

Coeliac disease associated with cerebellar ataxia and sensorimotor neuropathy; may be subclinical.

Tier 3 — Specialist Investigations

Specialist

Nerve conduction studies (NCS) and electromyography (EMG)

Gold standard for confirming neuropathy, distinguishing axonal from demyelinating patterns, identifying focal compression, and assessing severity. MBS item 11005 (nerve conduction studies). Available at most major Australian hospitals and private neurophysiology clinics; typical wait 2–8 weeks.

Specialist

Lumbar puncture (CSF analysis)

Albumino-cytological dissociation (elevated protein, normal cell count) supports GBS or CIDP. MBS item 11500.

Specialist

Skin punch biopsy (intraepidermal nerve fibre density)

Diagnosis of small-fibre neuropathy when NCS/EMG is normal. Available at select centres (e.g. Royal Melbourne Hospital, Royal Prince Alfred Hospital). MBS item 30100.

Specialist

Nerve biopsy (sural nerve)

Rarely required; reserved for suspected vasculitis, amyloidosis, or sarcoidosis when non-invasive tests are inconclusive. MBS item 30100.

Specialist

Genetic testing (CMT gene panel, PMP22 duplication)

Charcot–Marie–Tooth disease gene panels available through Australian clinical genetics services. CMT1A (PMP22 duplication) accounts for ~50% of CMT cases. MBS item 73294.

Specialist

Paraneoplastic antibody panel

Anti-Hu (ANNA-1), anti-CV2, anti-amphiphysin. Consider in subacute sensory neuronopathy with known or suspected malignancy. Available through specialised immunology laboratories.

Clinical Presentation & Diagnostic Criteria

Symptoms

The clinical presentation of peripheral neuropathy depends on the fibre types affected and the distribution of nerve involvement. Patients commonly present with a combination of positive and negative symptoms:

Positive sensory symptoms: Burning, tingling, "pins and needles," electric-shock sensations, allodynia (pain from non-painful stimuli), hyperalgesia. Often worse at night, disrupting sleep.
Negative sensory symptoms: Numbness, "dead" feeling in feet, loss of temperature sensation, reduced proprioception leading to unsteadiness.
Motor symptoms: Distal weakness (foot drop, difficulty rising from a chair), muscle wasting, cramps, fasciculations.
Autonomic symptoms: Orthostatic dizziness, resting tachycardia, gastroparesis (early satiety, nausea), constipation or diarrhoea, erectile dysfunction, urinary retention, gustatory sweating, dry eyes/mouth.

Examination Findings

A focused neurological examination should assess:

Sensation: Light touch (cotton wool), pinprick, vibration (128 Hz tuning fork on medial malleolus and great toe), proprioception (great toe), temperature (cold tuning fork or thermal roller).
Reflexes: Ankle jerbs are typically the first to be lost in length-dependent neuropathy. Symmetrically absent ankle jerbs with preserved knee jerbs is a classic early finding.
Motor: Great toe extension (L5 — extensor hallucis longus), foot dorsiflexion, toe walking, heel walking. Assess for interosseous wasting and pes cavus in chronic/hereditary cases.
Gait and balance: Romberg test, tandem gait (heel-to-toe walking). Sensory ataxia worsens when visual input is removed.
Autonomic: Lying and standing blood pressure (orthostatic drop ≥20 mmHg systolic or ≥10 mmHg diastolic), resting heart rate.
Foot examination: Calluses, ulcers, Charcot deformity (rocker-bottom foot), dry/cracked skin, fungal infections. Monofilament testing (10 g Semmes–Weinstein) for diabetic screening — loss of sensation at ≥1 site indicates at-risk foot (MBS item 2401 for annual diabetic foot check).

Diagnostic Criteria for Common Presentations

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Diabetic sensorimotor polyneuropathy (Toronto criteria): Requires (1) symptoms or signs of neuropathy, (2) abnormal nerve conduction studies in ≥2 nerves (one usually sural), and (3) exclusion of other causes. The Michigan Neuropathy Screening Instrument (MNSI) is a validated bedside screening tool.

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GBS (NINDS criteria): Required features — progressive, relatively symmetric weakness of limbs with areflexia. Supportive features — mild sensory signs, cranial nerve involvement, autonomic dysfunction, elevated CSF protein, NCS showing demyelination (AIDP pattern). Exclusions — pure sensory symptoms, bowel/bladder dysfunction at onset, polio, botulism.

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CIDP (EFNS/PNS 2021 criteria): Progressive or relapsing symmetric proximal and distal weakness with sensory impairment developing over ≥8 weeks, with NCS showing acquired demyelinating features (conduction block, temporal dispersion, prolonged distal latencies, slowed conduction velocities) and CSF protein >0.45 g/L.

Management of Painful Neuropathy

Painful peripheral neuropathy significantly impairs quality of life, sleep, mood, and functional capacity. Management should be multimodal, combining pharmacotherapy with non-pharmacological strategies and addressing comorbid sleep disturbance and mood disorders. The goal is ≥50% reduction in pain score (NRS/VAS) or meaningful improvement in function, with regular reassessment at 4–6 week intervals.

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Important: Opioids are not recommended for chronic neuropathic pain. They carry significant risks of dependence, tolerance, and opioid-induced hyperalgesia, with limited evidence of sustained benefit. Reserve for acute severe pain episodes or palliative situations only. Simple analgesics (paracetamol, NSAIDs) have minimal efficacy in neuropathic pain.

Pharmacological Management — Treatment Algorithm

1

First-Line Monotherapy

Gabapentinoid (pregabalin or gabapentin) OR SNRI (duloxetine). Choose based on comorbidities: gabapentinoids for comorbid anxiety/insomnia; duloxetine for comorbid depression or anxiety.

2

Optimise Dose or Switch Class

If inadequate response at adequate dose after 4–8 weeks, switch to the other first-line class or consider combination therapy. Add topical agent for localised areas.

3

Second-Line / Combination

TCA (amitriptyline or nortriptyline) — avoid in elderly/cardiac disease. Combination: gabapentinoid + SNRI or gabapentinoid + low-dose TCA. Tramadol may be considered short-term for refractory pain.

4

Specialist Referral

If pain remains refractory despite two adequate trials, refer to a pain medicine specialist or neurologist. Consider capsaicin 8% patch, lignocaine patches, spinal cord stimulation, or intrathecal therapies.

First-Line Agents

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Pregabalin

Lyrica® · Generic available · α2δ calcium channel ligand

Adult dose Start 75 mg PO BD, titrate to 150 mg BD over 1 week; max 300 mg BD (600 mg/day). Reduce dose in renal impairment.

Paediatric dose Not recommended <18 years for neuropathic pain (limited data)

Renal adjustment eGFR 30–60: max 150 mg BD. eGFR 15–30: 25–75 mg BD. eGFR <15: 25 mg OD. Dialysis: 25–50 mg OD + post-dialysis supplement.

Hepatic adjustment Not hepatically metabolised — no adjustment required

Key side effects Somnolence, dizziness, weight gain, peripheral oedema. Risk of misuse — Schedule 4 in Australia.

PBS status ✔ PBS General Benefit — Authority Required for neuropathic pain >3 months

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Gabapentin

Neurontin® · Generic available · α2δ calcium channel ligand

Adult dose Start 300 mg PO nocte, titrate to 300 mg TDS over 1–2 weeks; target 1800–3600 mg/day in divided doses (TDS). Start low, go slow.

Paediatric dose Limited data; specialist supervision if used

Renal adjustment eGFR 30–59: max 600 mg BD. eGFR 15–29: max 300 mg OD. eGFR <15: 300 mg alternate days. Dose after haemodialysis.

Hepatic adjustment Not hepatically metabolised — no adjustment required

Key side effects Dizziness, somnolence, weight gain, peripheral oedema. TID dosing may reduce compliance.

PBS status ✔ PBS General Benefit — Authority Required for neuropathic pain

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Duloxetine

Cymbalta® · Generic available · SNRI

Adult dose Start 30 mg PO OD for 1 week, then increase to 60 mg OD. Maximum 120 mg/day (though 60 mg is usually sufficient for neuropathic pain).

Paediatric dose Not recommended <18 years for neuropathic pain

Renal adjustment eGFR <30: avoid or use with caution (limited data)

Hepatic adjustment Avoid in severe hepatic impairment (Child-Pugh C)

Key side effects Nausea (most common initially, improves in 1–2 weeks), dry mouth, constipation, dizziness, increased sweating. Avoid with MAOIs. Caution in uncontrolled hypertension.

PBS status ✔ PBS General Benefit — Authority Required for neuropathic pain

Second-Line Agents

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Amitriptyline

Endep® · Generic available · TCA (tertiary amine)

Adult dose Start 10–25 mg PO ON at night, titrate gradually to 50–150 mg ON. Lower doses (10–50 mg) often effective for neuropathic pain compared to antidepressant doses.

Paediatric dose Not recommended for neuropathic pain in children

Renal adjustment No specific adjustment, but use lower doses

Hepatic adjustment Avoid in severe hepatic impairment

Key side effects Anticholinergic effects (dry mouth, constipation, urinary retention, blurred vision), sedation, weight gain, QT prolongation. Cardiac risk: ECG baseline in patients >50 years or with cardiac history. Avoid in patients with QTc >470 ms.

PBS status ✔ PBS General Benefit

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Nortriptyline

Allegron® · Generic available · TCA (secondary amine)

Adult dose Start 10–25 mg PO ON at night, titrate to 50–150 mg ON. May be better tolerated than amitriptyline with less sedation and fewer anticholinergic effects.

Paediatric dose Not recommended for neuropathic pain in children

Renal adjustment No specific adjustment

Hepatic adjustment Use with caution in hepatic impairment

Key side effects Less sedating than amitriptyline; still carries QT prolongation risk. Therapeutic drug monitoring available (target 200–600 nmol/L).

PBS status ✔ PBS General Benefit

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Venlafaxine

Effexor-XR® · Generic available · SNRI

Adult dose Start 37.5 mg PO OD (extended release), titrate to 150–225 mg OD. At lower doses, primarily serotonergic; noradrenergic effect at ≥150 mg.

Renal adjustment eGFR 10–30: reduce dose by 50%

Hepatic adjustment Reduce dose by 50% in hepatic impairment

Key side effects Nausea, dizziness, hypertension (dose-related — monitor BP), discontinuation syndrome. Must taper gradually.

PBS status ✔ PBS General Benefit — for depression; neuropathic pain is off-label but supported by evidence

Topical Therapies

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Capsaicin 8% Patch

Qutenza® · TRPV1 receptor agonist (defunctionalisation)

Dose Applied by healthcare professional for 30 minutes (peripheral neuropathy) or 60 minutes (postherpetic neuralgia) to affected area. Repeat every 3 months as needed.

Indication Refractory localised peripheral neuropathic pain (e.g. focal painful diabetic neuropathy of the feet)

Key side effects Application site pain (transient, usually 1–2 hours), erythema. Topical anaesthetic may be applied pre-treatment.

PBS status ⚠ PBS Authority Required — for refractory neuropathic pain failing ≥2 systemic agents

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Lignocaine 5% Medicated Plaster

Versatis® · Local anaesthetic (sodium channel blocker)

Dose Apply up to 3 plasters to the affected area for up to 12 hours in a 24-hour period. Avoid on broken or inflamed skin.

Indication Localised neuropathic pain, particularly postherpetic neuralgia; useful as adjunctive therapy in peripheral neuropathy

Key side effects Application site reactions (erythema, pruritus). Systemic absorption minimal with intact skin.

PBS status ✘ Not PBS listed — available at patient's expense (~$80–120 per pack of 30)

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Capsaicin 0.075% Cream

Zacin® · TRPV1 agonist

Dose Apply TDS–QID to affected area. Effects develop over 2–4 weeks of regular use. Patient must persist despite initial burning.

Indication Mild localised neuropathic pain; less effective than 8% patch

Key side effects Application site burning (common initially, diminishes with continued use). Avoid contact with eyes and mucous membranes. Wash hands thoroughly.

PBS status ✔ PBS General Benefit

Sleep and Mood Considerations

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Neuropathic pain and mental health are closely interlinked. Up to 50% of patients with chronic painful neuropathy develop clinically significant depression and/or anxiety. Insomnia is almost universal. Screen with PHQ-9 and GAD-7 at baseline and follow-up. Address sleep hygiene as a priority — poor sleep amplifies central sensitisation and pain perception.

Sleep: Non-pharmacological measures include sleep hygiene education, cognitive behavioural therapy for insomnia (CBT-I), and avoiding daytime napping. Pregabalin and amitriptyline may improve sleep through their sedating properties. Avoid benzodiazepines and Z-drugs long-term.
Depression/Anxiety: Duloxetine is the preferred agent when comorbid depression exists. Consider psychology referral (MBS items 80110/80115 for Mental Health Treatment Plan). Safety-net for suicidal ideation with regular follow-up.
Exercise: Moderate-intensity aerobic exercise (≥150 minutes/week) improves neuropathic pain severity, mood, and cardiovascular fitness. Refer to exercise physiologist where available.
Alcohol cessation: Essential in alcohol-related neuropathy; refer to addiction medicine or local alcohol and drug service. Thiamine replacement (100 mg PO BD) in addition to addressing nutrition.

Non-Pharmacological Approaches

Transcutaneous electrical nerve stimulation (TENS): May provide short-term relief; minimal side effects. Available OTC. PBS not applicable.
Physiotherapy and balance training: Reduces fall risk; important in sensory ataxia and large-fibre neuropathy. Physiotherapy referral (MBS item 10950–10970).
Occupational therapy: Footwear assessment, orthotics, assistive devices, and home safety modifications.
Foot care education: Daily foot inspection, appropriate footwear, avoid walking barefoot, regular podiatry review (MBS item 10950 for diabetic foot care).

Mononeuropathies

Focal mononeuropathies are common in clinical practice and are most frequently caused by compression or entrapment at anatomical sites of vulnerability. The three most frequently encountered mononeuropathies in Australian primary care are carpal tunnel syndrome (median nerve), ulnar neuropathy at the elbow, and peroneal neuropathy at the fibular head.

Carpal Tunnel Syndrome (Median Neuropathy at the Wrist)

Feature	Details
Epidemiology	Most common entrapment neuropathy; prevalence 3–5% of the Australian adult population. More common in women (3:1), age 40–60 years. Bilateral in up to 50%.
Risk factors	Repetitive wrist flexion/extension, vibration tool use, pregnancy, obesity, diabetes, hypothyroidism, rheumatoid arthritis, wrist fracture (history), haemodialysis, hereditary neuropathy with liability to pressure palsies (HNPP).
Symptoms	Numbness, tingling, and pain in the median nerve distribution (thumb, index, middle, and radial half of ring finger). Symptoms typically nocturnal, often waking the patient; relieved by shaking/flicking the wrist ("flick sign"). May radiate proximally to the forearm and shoulder.
Examination	Tinel sign (percussion over carpal tunnel), Phalen manoeuvre (forced wrist flexion for 60 seconds), thenar wasting (late finding), reduced two-point discrimination in median nerve distribution. Sensitivity of provocative tests is moderate (50–70%); confirm with NCS.
NCS confirmation	Prolonged distal motor latency of median nerve (>4.2 ms) and/or reduced sensory conduction velocity across the carpal tunnel compared to ulnar nerve. MBS item 11005. Severity grading guides management.

Carpal Tunnel — Conservative Management

Wrist splinting: Neutral-position wrist splint worn at night for ≥6 weeks. Most effective for mild-to-moderate symptoms. Available OTC (~$20–40). First-line for pregnancy-related CTS.
Ergonomic modification: Avoid sustained wrist flexion/extension; ergonomic keyboard/mouse; work station assessment (refer to occupational therapist).
Corticosteroid injection: Methylprednisolone 40 mg or triamcinolone 20 mg injected into the carpal tunnel (MBS item 18350). Provides short-to-medium term relief (6–12 weeks). May be repeated once. Does not alter long-term course. Useful as a bridge to surgery or diagnostic trial.
Treat underlying causes: Thyroid function, glycaemic control, weight management, rheumatological disease management.

Carpal Tunnel — When to Refer for Surgery

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Indications for surgical referral (carpal tunnel release):

Failure of conservative management (splinting ± injection) after ≥6–8 weeks
Severe NCS findings (absent sensory responses, prolonged motor latency >6.5 ms)
Thenar wasting or significant motor weakness (inability to oppose thumb)
Persistent numbness or constant symptoms (not just nocturnal)
Patient preference for definitive treatment

Carpal tunnel release (open or endoscopic) has a success rate of >90%. Endoscopic release may allow earlier return to work. Performed by hand surgeon, orthopaedic surgeon, or plastic surgeon. MBS item 49824.

Ulnar Neuropathy at the Elbow (Cubital Tunnel Syndrome)

Feature	Details
Epidemiology	Second most common entrapment neuropathy. More common in men. Associated with prolonged elbow flexion, resting elbow on hard surfaces, cubitus valgus (post-fracture), rheumatoid arthritis.
Symptoms	Tingling and numbness in the ring and little fingers (ulnar 1½ fingers), medial forearm. May experience medial elbow pain. Worsened by elbow flexion (e.g. phone use, driving). Wasting of intrinsic hand muscles (interossei, hypothenar muscles) in advanced cases — grip weakness, difficulty with fine motor tasks (e.g. opening jars).
Examination	Tinel sign at the cubital tunnel, Froment sign (flexion of thumb IP joint during lateral pinch — weakness of adductor pollicis), Wartenberg sign (abducted little finger — weakness of third palmar interosseous), claw hand deformity (MCP extension with IP flexion of ring and little fingers in severe cases). Test sensation over dorsal ulnar hand (dorsal cutaneous branch — spared if entrapment is at Guyon canal).
Diagnosis	NCS showing slowing of ulnar nerve conduction across the elbow (<50 m/s or >10 m/s drop from above to below elbow). MBS item 11005.

Ulnar Neuropathy — Conservative Management

Activity modification: Avoid prolonged elbow flexion (>90°), avoid leaning on elbow, avoid holding phone to ear — use speakerphone or headset. Pad elbow when resting on desks.
Elbow splinting: Night-time elbow extension splint (maintain at 45° flexion) for 6–12 weeks. May improve mild-to-moderate symptoms.
Physiotherapy: Nerve gliding exercises (ulnar nerve glide technique), strengthening of affected muscles, ergonomic advice.

Ulnar Neuropathy — When to Refer for Surgery

Failure of conservative management after 3 months
Intrinsic hand muscle wasting or weakness on examination
Severe NCS findings (absent responses, marked slowing)
Progressive symptoms despite activity modification

Surgical options include simple decompression, anterior transposition (submuscular or subcutaneous), or medial epicondylectomy. Anterior transposition is preferred for subluxating ulnar nerve or severe cases. MBS item 49826. Prognosis depends on severity at the time of surgery — motor recovery is less predictable if significant wasting is present.

Peroneal Neuropathy at the Fibular Head (Common Peroneal Nerve)

Feature	Details
Epidemiology	Most common lower limb mononeuropathy. Risk factors: significant weight loss (loss of protective perineural fat), prolonged bed rest/immobilisation, leg crossing, kneeling, plaster cast application, bariatric surgery, lithotomy position during surgery.
Symptoms	Foot drop (difficulty dorsiflexing the foot) and ankle eversion weakness. Numbness over the dorsum of the foot and lateral leg. High-stepping gait to compensate. Patients may report tripping or scuffing the foot while walking.
Examination	Weakness of ankle dorsiflexion (tibialis anterior — L4/L5), great toe dorsiflexion (extensor hallucis longus), ankle eversion (peronei — L5/S1). Ankle inversion is preserved (tibial nerve — S1). Reduced sensation over the lateral leg and dorsum of the foot. Reflexes are typically preserved (ankle jerk innervated by tibial nerve). Tinel sign at the fibular head.
Diagnosis	NCS showing reduced amplitude or absent superficial peroneal sensory response and/or prolonged distal motor latency or reduced CMAP amplitude of the peroneal nerve. Motor conduction across the fibular head shows localised slowing. MBS item 11005.

Peroneal Neuropathy — Conservative Management

Address the cause: Avoid leg crossing, avoid kneeling, pad the fibular head when sitting (e.g. wheelchair users), change positions frequently.
Ankle-foot orthosis (AFO): A lightweight AFO or foot-drop splint maintains the foot in a neutral position, improving gait and preventing falls. Prescribed by rehabilitation physician or orthotist. MBS item 10950–10970 (physiotherapy) and MBS item 19500 (orthotic prescription).
Physiotherapy: Strengthening of dorsiflexors and evertors, gait retraining, balance exercises. Referral to physiotherapist or exercise physiologist.
Monitoring: Most compression peroneal neuropathies recover spontaneously over 3–6 months with conservative management. Serial NCS at 3-month intervals to track recovery if no clinical improvement.

Peroneal Neuropathy — When to Refer for Surgery

No clinical improvement after 3–4 months of conservative management
Identifiable compressive mass (e.g. ganglion cyst, tumour) requiring excision
Complete foot drop with absent motor responses on NCS after 3 months
Traumatic nerve injury (laceration, fracture) — early surgical exploration

Surgical decompression of the common peroneal nerve at the fibular head may be performed by a peripheral nerve surgeon. MBS item 49824. Functional electrical stimulation (FES) devices for foot drop may be considered as an alternative to AFO in selected patients.

Mononeuropathy	Nerve Root	Key Clinical Test	Conservative Tx Duration	Surgery Indication
Carpal tunnel	Median (C6–T1)	Phalen, Tinel, thenar strength	6–8 weeks	Failure conservative Rx, motor weakness, severe NCS
Ulnar at elbow	Ulnar (C8–T1)	Froment, interosseous wasting	3 months	Muscle wasting, severe NCS, progressive symptoms
Peroneal at fibular head	Common peroneal (L4–S1)	Foot drop, eversion weakness, Tinel at fib head	3–4 months	No recovery at 4 months, identifiable mass, trauma

Monitoring

Regular monitoring is essential to assess treatment efficacy, detect disease progression, manage side effects, and reduce complications such as falls and foot ulceration.

Monitoring Schedule

Baseline

Comprehensive neurological examination, pain score (NRS 0–10), functional assessment (e.g. Norfolk QOL-DN for diabetic neuropathy), baseline ECG if starting TCA, baseline renal function (for gabapentinoid dosing), PHQ-9/GAD-7 screening, fall risk assessment, monofilament testing, footwear assessment.

4–6 weeks

Reassess pain response (target ≥30% reduction). Titrate medications. Check for side effects (sedation, weight gain with gabapentinoids; nausea with duloxetine; anticholinergic effects with TCAs). Review sleep quality.

12 weeks

Reassess pain response (target ≥50% reduction). If inadequate response, switch or combine agents. Repeat ECG if TCA dose adjusted. Renal function check if on gabapentinoid (or if eGFR was borderline).

6 months

Comprehensive review. Consider need for ongoing medication. Repeat HbA1c if diabetic. Assess for disease progression (new neurological deficits). Foot examination (annual minimum for diabetic patients; more frequent if high-risk feet). Refer to pain specialist or neurologist if refractory.

Ongoing (6–12 monthly)

Stable patients: annual neurological review, annual diabetic foot check (MBS item 2401), ongoing medication review, fall risk reassessment. Monofilament testing annually for diabetic patients. Repeat NCS only if clinical change suspected.

Complications to Monitor

Falls: Peripheral neuropathy is an independent risk factor for falls. Use the Timed Up and Go (TUG) test or Physiological Profile Assessment (PPA). Refer to falls prevention programme if TUG >12 seconds.
Foot ulceration: Annual monofilament testing in diabetic patients (MBS item 2401). High-risk feet: podiatry review every 3 months, appropriate footwear, daily self-inspection education.
Charcot neuroarthropathy: Acute hot, swollen, red foot in a patient with peripheral neuropathy — consider Charcot until proven otherwise. Urgent plain X-ray and MRI. Refer to endocrinology/orthopaedics. RHDAustralia guidelines apply for management.
Autonomic neuropathy: Orthostatic hypotension, resting tachycardia, gastroparesis, erectile dysfunction. Annual screening in diabetic patients. Assess lying and standing blood pressure at each visit.

Special Populations

🤰

Pregnancy

Carpal tunnel syndrome is very common in pregnancy (up to 30–60% in the third trimester) due to fluid retention. Usually self-limiting — resolves postpartum in most cases.

Management: Conservative measures first — wrist splinting, ergonomic modification. Corticosteroid injection may be considered if severe and affecting function.

⚠️ Pregabalin: Avoid in pregnancy (Category B3 — limited human data; animal studies show developmental toxicity). Duloxetine: Category B2 — use only if benefits outweigh risks; neonatal withdrawal possible in third trimester.

⚠️ Amitriptyline: Category C — use with caution; neonatal withdrawal symptoms reported. Avoid in third trimester if possible.

✅ Safe options: Paracetamol, physical therapy, splinting, TENS. Gabapentin has limited data but may be considered under specialist guidance if severe refractory pain.

Refer to obstetric medicine or maternal-fetal medicine specialist for neuropathic pain management in pregnancy. Avoid nerve conduction studies during pregnancy unless essential (theoretical concern, though no proven risk).

👶

Paediatrics

Peripheral neuropathy in children is uncommon and requires thorough investigation for hereditary causes (CMT — most common), inflammatory/infectious causes (GBS), and metabolic conditions (Fabry disease, leucodystrophies).

Hereditary neuropathies (CMT) should be suspected in a child with pes cavus, hammer toes, difficulty running, distal weakness, and a positive family history. Referral to paediatric neurology for genetic testing is essential.

⚠️ Pregabalin/gabapentin: Not approved for neuropathic pain in children <18 years. If required, specialist management only.

⚠️ Duloxetine: Not approved <18 years for neuropathic pain. TCA use in children is restricted.

All children with peripheral neuropathy should be referred to a paediatric neurologist. NCS/EMG in children requires experienced paediatric neurophysiology services (available at major children's hospitals — RCH Melbourne, CHW Sydney, QCH Brisbane).

👴

Elderly (≥65 years)

Peripheral neuropathy prevalence increases significantly with age, even in non-diabetic populations. Age-related "senile" neuropathy is a mild sensory axonal neuropathy of uncertain significance.

Polypharmacy risk: Carefully review medication list for neuropathy-inducing drugs — metronidazole, isoniazid, nitrofurantoin, phenytoin, vincristine, amiodarone, colchicine, statins (rare).

⚠️ Amitriptyline: Avoid in patients >65 years (Beers criteria — high anticholinergic burden, falls risk, QT prolongation, cognitive impairment). If TCA required, prefer nortriptyline at lower doses with ECG monitoring.

⚠️ Gabapentinoids: Start at lower doses (pregabalin 25–50 mg BD, gabapentin 100–200 mg OD) due to increased sensitivity to CNS side effects and reduced renal clearance. Falls risk is significantly increased.

⚠️ Duloxetine: Start at 30 mg OD, titrate cautiously. Monitor for hyponatraemia (SIADH risk) and blood pressure elevation.

Falls prevention is a priority. Assess lying/standing blood pressure, home safety, and mobility aids. Regular podiatry referral for foot care. Multidisciplinary team approach involving GP, neurologist, physiotherapist, podiatrist, and occupational therapist.

🫘

Renal Impairment

Uraemic neuropathy develops in CKD stages 4–5 (eGFR <30 mL/min/1.73 m²), particularly in patients approaching dialysis. Distal symmetric sensorimotor pattern. May improve with renal transplant.

Both gabapentin and pregabalin are renally cleared — mandatory dose reduction. Pregabalin is removed by haemodialysis — supplemental dose required post-dialysis.

⚠️ Pregabalin: eGFR 30–60: max 150 mg BD. eGFR 15–30: 25–75 mg BD. eGFR <15: 25 mg OD. HD: dose post-dialysis.

⚠️ Gabapentin: eGFR 30–59: max 600 mg BD. eGFR 15–29: 300 mg OD. eGFR <15: 300 mg alternate days. HD: 300 mg post-dialysis.

⚠️ Duloxetine: Avoid if eGFR <30 mL/min/1.73 m² (limited data and hepatic metabolite accumulation).

Amitriptyline/nortriptyline: no specific renal adjustment, but lower starting doses. Refer to nephrology for uraemic neuropathy management. Dialysis adequacy optimisation may improve symptoms.

🫁

Hepatic Impairment

Alcoholic liver disease is frequently associated with peripheral neuropathy from combined direct alcohol toxicity and nutritional deficiency (thiamine, B12, folate).

⚠️ Duloxetine: Contraindicated in severe hepatic impairment (Child-Pugh C). Avoid in significant liver disease due to hepatotoxicity risk.

⚠️ Amitriptyline/nortriptyline: Reduce dose in hepatic impairment; increased risk of drug accumulation and hepatotoxicity. Monitor LFTs.

Pregabalin and gabapentin: no hepatic metabolism — safe in hepatic impairment (preferred agents in this population). Address underlying liver disease and nutritional deficiency. Thiamine 100 mg PO/IV BD for all patients with alcohol-related liver disease.

🛡️

Immunocompromised

HIV-associated distal sensory polyneuropathy (DSPN) is the most common neurological complication of HIV. Also consider cytomegalovirus (CMV) polyradiculopathy — acute onset, ascending weakness — requires urgent treatment with ganciclovir.

Post-transplant neuropathy may be related to immunosuppressant toxicity (tacrolimus — especially painful small-fibre neuropathy) or chronic rejection-mediated vasculitis.

Chemotherapy-induced peripheral neuropathy (CIPN) — dose-limiting toxicity of platinum agents (oxaliplatin, cisplatin), taxanes (paclitaxel), vinca alkaloids (vincristine), bortezomib, and thalidomide. Discuss dose modification with oncologist.

All first-line neuropathic pain agents may be used; drug interactions with antiretrovirals should be checked (particularly duloxetine with ritonavir). Refer to infectious diseases or transplant physician for complex cases.

Aboriginal and Torres Strait Islander Health

Aboriginal and Torres Strait Islander Health Considerations

Higher disease burden

Aboriginal and Torres Strait Islander Australians have 3.5 times the rate of diabetes-related lower limb amputation compared to non-Indigenous Australians (AIHW 2023). Peripheral neuropathy is a major contributing factor. Type 2 diabetes prevalence is 3–4 times higher in Indigenous Australians, with earlier onset and more aggressive complications.

Remote access challenges

Nerve conduction studies (NCS/EMG) are not available in most remote communities. Telehealth assessment via neurologist may assist with clinical decision-making. Royal Flying Doctor Service (RFDS) and visiting specialist outreach programmes are essential for access to neurophysiology services. Waiting times for NCS may be 3–6 months in regional and remote areas.

Foot care programmes

High-risk foot services, as outlined by RHDAustralia (Remote Area Health Corps) and the National Aboriginal Community Controlled Health Organisation (NACCHO), are critical. Annual diabetic foot checks should be incorporated into chronic disease management plans (MBS item 721/723). Community-controlled health services should have trained Aboriginal health practitioners to perform monofilament testing and basic foot care.

Cultural safety

Engage Aboriginal and Torres Strait Islander health workers in neuropathy education, foot care, and medication discussions. Use culturally appropriate health promotion materials. Recognise the importance of family, community, and Country in health decision-making. Ensure continuity of care through trusted healthcare providers.

Alcohol and substance use

Alcohol-related neuropathy is a significant contributor in some communities. Interventions must be trauma-informed and culturally safe. Referral to Aboriginal Community Controlled Health Organisations (ACCHOs) for alcohol and drug support services. Address social determinants of health.

Medication access

Pregabalin and duloxetine are PBS-listed but may be difficult to access in remote communities without regular pharmacy supply. Close-the-Gap PBS co-payment ensures no out-of-pocket cost for eligible patients. Ensure prescriptions are written for dispensing through remote area Aboriginal health services. Medication adherence support through Aboriginal health workers is essential.

📚 References

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2. Callaghan BC, Price RS, Feldman EL. Diagnostic and therapeutic advances in the assessment and treatment of diabetic peripheral neuropathy. JAMA. 2015;314(10):1054–1055. doi:10.1001/jama.2015.9079
3. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162–173. doi:10.1016/S1474-4422(14)70251-0
4. Pop-Busui R, Boulton AJM, Feldman EL, et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care. 2017;40(1):136–154. doi:10.2337/dc16-2042
5. Australian Institute of Health and Welfare (AIHW). Diabetes: Australian Facts. Canberra: AIHW; 2023. Cat. no. CVD 83.
6. Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force. J Peripher Nerv Syst. 2021;26(3):251–263.
7. National Health and Medical Research Council (NHMRC). National Evidence-Based Guideline for Prevention, Identification and Management of Foot Complications in Diabetes. Melbourne: NHMRC; 2011.
8. Royal Australian College of General Practitioners (RACGP). Management of Type 2 Diabetes: A Handbook for General Practice. Melbourne: RACGP; 2020.
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10. Burns J, Ouvrier R, Estilow T, et al. Validation of the Charcot–Marie–Tooth disease pediatric scale as an outcome measure of disability. Ann Neurol. 2012;71(5):642–652. doi:10.1002/ana.23572
11. Traub R, Xiao J, Leung E, et al. Australian burden of disease study: impact and causes of illness and death in Aboriginal and Torres Strait Islander people 2018. Aust N Z J Public Health. 2023;47(2):100028.
12. RHDAustralia (Remote Area Health Corps). Standard Treatment Manual for Primary Health Care. 6th ed. Darwin: RHDAustralia; 2022.
13. Padua L, Coraci D, Erra C, et al. Carpal tunnel syndrome: clinical features, diagnosis, and management. Lancet Neurol. 2016;15(12):1273–1284. doi:10.1016/S1474-4422(16)30231-9
14. Pharmaceutial Benefits Advisory Committee (PBAC). PBS Schedule. Canberra: Department of Health and Aged Care; 2024.