Numbness or altered sensation
Red flags
- Sensory level on the trunk +/- bladder or bowel change = cord compression - MRI whole spine today, dexamethasone if malignant
- Saddle anaesthesia + bilateral sciatica + urinary retention = cauda equina - MRI today
- Rapidly ascending numbness and weakness with areflexia = GBS - serial FVC, not oximetry
- Sudden onset, one side, face + arm + leg = stroke or TIA - code stroke pathway
- Pure sensory stroke = thalamic or internal capsule lacune
- Numbness with fever, back pain and raised inflammatory markers = epidural abscess
- Dissociated sensory loss (pain/temperature lost, proprioception spared) = intramedullary cord lesion until excluded
- New numbness in a patient with cancer = metastasis, leptomeningeal disease, paraneoplastic, or chemotherapy toxicity
- Nitrous oxide use, bariatric surgery, or vegan diet with a spastic-ataxic gait = B12 deficiency - treat before the deficit becomes fixed
- Painless ulceration, burns or Charcot joint - the sensory loss is already dangerous
Differential by mechanism
Step 1 - localise by the PATTERN, not the cause
| Pattern | Localisation | Causes |
|---|---|---|
| Total unilateral loss of ALL modalities | Thalamus or upper brainstem | Infarct, haemorrhage, tumour, demyelination. "Pure sensory stroke" = VPL thalamic lacune |
| All modalities lost in a well-defined area | Posterior nerve root, or a peripheral nerve | Radiculopathy (disc, zoster, malignancy); mononeuropathy. A peripheral nerve lesion usually also has a motor deficit; a root lesion follows a dermatome |
| Isolated spinothalamic loss (pain + temperature) | Anterior cord, central cord, or small fibres | Syringomyelia (cape distribution, suspended, dissociated), Brown-Sequard - CONTRALATERAL leg, anterior spinal artery thrombosis, lateral medullary syndrome (contralateral to the other signs, face ipsilateral), small-fibre peripheral neuropathy |
| Isolated dorsal column loss (vibration + proprioception) | Posterior columns or large fibres | Subacute combined degeneration, Brown-Sequard - IPSILATERAL leg, Friedreich ataxia and other spinocerebellar degenerations, MS, tabes dorsalis, large-fibre peripheral neuropathy, sensory neuronopathy (dorsal root ganglionopathy) - carcinoma, diabetes, Sjogren syndrome, cisplatin, B6 excess |
| Glove-and-stocking, symmetric, length-dependent | Peripheral nerve | Diabetes, alcohol, B12, uraemia, hypothyroid, drugs, paraprotein, hereditary |
| Sensory level on the trunk | Spinal cord | Compression, transverse myelitis, infarct, tumour, abscess |
| Mononeuritis multiplex (asymmetric, sequential named nerves) | Vasa nervorum | Vasculitis, diabetes, leprosy, sarcoid, HIV, cryoglobulinaemia, amyloid |
| Perioral + hands, symmetrical, episodic | Metabolic | Hyperventilation, hypocalcaemia, hypomagnesaemia |
| Non-anatomical, splitting the midline exactly, vibration "stopping" at the sternum | Functional | A positive diagnosis, made on positive signs - not a diagnosis of exclusion |
Step 2 - then ask the time course
- Seconds-minutes -> vascular (stroke/TIA), seizure (Jacksonian march over seconds), migraine aura (march over 20-30 min, positive symptoms)
- Hours-days -> inflammatory, compressive, infective
- Weeks-months -> tumour, degenerative, nutritional, toxic
- Years, distal, symmetric -> metabolic or hereditary polyneuropathy
Focused history
Define it
- "Numb, or pins and needles, or does it hurt?"
- Negative symptoms (loss, deadness) -> a destructive lesion
- Positive symptoms (tingling, burning, electric, allodynia) -> irritative/neuropathic
- Exact distribution - ask the patient to trace it with a finger; whether it crosses the midline and where it stops is diagnostic
- Onset, march, duration, remission, relapse
- Associated weakness, gait change, clumsiness, bladder/bowel/sexual dysfunction
- Lhermitte sign (electric shock down the spine on neck flexion) -> dorsal columns, cervical cord
- Pain: back pain (root, cord), neck pain (dissection, cord)
Cause-directed
- Diabetes, alcohol, thyroid, renal disease
- Diet - vegan, bariatric surgery, nitrous oxide ("nangs") use -> B12
- Drugs - chemotherapy (platins, taxanes, vincristine, bortezomib, thalidomide), metronidazole, isoniazid, nitrofurantoin, amiodarone, phenytoin, excess pyridoxine
- Sicca symptoms, rash, arthralgia, Raynaud -> connective tissue disease, vasculitis
- Weight loss, night sweats, smoking -> malignancy, paraneoplastic
- Family history and look at the patient's parents' feet -> hereditary neuropathy
- Occupational and vibration exposure; repetitive activity; recent travel; HIV risk
- Previous episodes of neurological symptoms that resolved -> MS
Focused examination
Map it before you name it
1. Sensory testing to the modality
- Pinprick and temperature (spinothalamic) and vibration (128 Hz tuning fork) and joint position sense (dorsal column) - always test both systems separately; dissociation is the whole game
- Light touch, two-point discrimination
- Work from abnormal to normal for numbness, and normal to abnormal for hyperaesthesia
- Define the upper level on the trunk anteriorly and posteriorly (the cord level is often 1-2 segments above the sensory level)
2. Romberg - falls with eyes closed = proprioceptive (dorsal column) loss, not cerebellar
3. Reflexes - absent = LMN/root/nerve; brisk with upgoing plantars = cord or above
4. Power by myotome, tone, wasting, fasciculation
5. Gait - high-stepping (foot drop), spastic-ataxic (SCDC), sensory ataxic (stamping)
Then look for the cause
- Palpate peripheral nerves (ulnar, common peroneal, greater auricular) - thickened in CMT1, leprosy, amyloid, CIDP
- Feet: pes cavus and clawing (hereditary), ulcers, callus, Charcot joint, pulses
- Skin: vasculitic purpura, rash, zoster, angiokeratoma (Fabry), hypopigmented anaesthetic patches (leprosy)
- Tinel and Phalen at the wrist; Spurling for cervical root
- Fundoscopy (optic atrophy - MS, B12), pupils (Argyll Robertson - tabes)
- Cranial nerves: crossed sensory loss (face one side, body the other) = lateral medulla
- General: lymphadenopathy, hepatosplenomegaly, breast/prostate/testicular examination, glossitis, koilonychia
Investigation strategy
First-line in almost everyone
- FBE, UEC, LFT, HbA1c or OGTT, TFT, B12 and active B12/homocysteine + methylmalonic acid, folate
- ESR/CRP, serum protein electrophoresis + immunofixation + serum free light chains (paraprotein is a common and reversible cause - do not omit it)
- Copper and caeruloplasmin if myelopathy or a history of bariatric surgery or zinc excess
Directed by the localisation
| Localisation | Test |
|---|---|
| Brain/brainstem/thalamus | CT then MRI brain; CTA/MRA if vascular; stroke work-up (ECG, echo, carotids) |
| Spinal cord | MRI whole spine with gadolinium - urgently if a level or sphincter involvement. Then CSF (cells, protein, OCB), AQP4 and MOG antibodies, B12, copper, HTLV-1, syphilis |
| Root | MRI of the relevant spine segment; EMG/NCS at >=3 weeks (paraspinal denervation, preserved SNAPs) |
| Plexus | MRI brachial/lumbosacral plexus, CT chest for apical tumour, EMG/NCS |
| Peripheral nerve | NCS/EMG - the pivotal test: demyelinating vs axonal, symmetric vs multifocal |
| Small fibre | Skin biopsy for intraepidermal nerve fibre density, quantitative sensory testing, autonomic testing (NCS are normal - a normal NCS does NOT exclude neuropathy) |
Second-line when the cause is unclear
- HIV, hepatitis B and C, syphilis serology; cryoglobulins, hepatitis C if vasculitic
- ANA/ENA (anti-Ro/La for Sjogren), ANCA, rheumatoid factor, complement
- Anti-ganglioside antibodies (GM1 for multifocal motor neuropathy, GQ1b for Miller Fisher), anti-MAG if IgM paraprotein
- Paraneoplastic and autoimmune encephalitis panel (anti-Hu for sensory neuronopathy, CV2/CRMP5, amphiphysin) + CT chest/abdomen/pelvis +/- PET
- Genetic testing - PMP22 first if demyelinating; transthyretin (ATTRv) if progressive axonal with autonomic, cardiac or carpal tunnel features
- Nerve biopsy (sural) - reserved for suspected vasculitis, amyloid or atypical CIDP
Management
A. Treat the cause - this is where the benefit is
| Cause | Action |
|---|---|
| Cord/cauda equina compression | Urgent decompression +/- dexamethasone and radiotherapy |
| Stroke | Acute stroke pathway then secondary prevention |
| B12 deficiency / nitrous oxide | IM hydroxocobalamin without waiting for confirmation; stop nitrous oxide. Give B12 before folate - folate alone precipitates SCDC |
| Diabetes | Glycaemic control plus the other metabolic risk factors - tight glycaemia prevents neuropathy in type 1, far less so in type 2 |
| Alcohol | Abstinence + thiamine, then broad B group and nutrition |
| CIDP / MMN / GBS | IVIg (steroids work in CIDP but WORSEN multifocal motor neuropathy), plasma exchange |
| Vasculitis | Corticosteroid + cyclophosphamide or rituximab |
| Paraprotein / amyloid | Haematology referral; treat the clone; ATTRv - tafamidis, patisiran, vutrisiran |
| Drug-induced | Stop or substitute; document the dose at which it started |
| Entrapment | Splinting, activity modification, injection, decompression |
B. Neuropathic pain - if present
- First-line: amitriptyline, duloxetine, gabapentin or pregabalin - equivalent efficacy, choose by comorbidity
- Amitriptyline 10 mg nocte (5 mg if frail), inc by 10 mg every 5-7 days to 25-75 mg - anticholinergic, falls, urinary retention, QT
- Duloxetine 30 mg daily -> 60 mg - best evidence in diabetic neuropathy; also treats comorbid depression
- Gabapentin 300 mg nocte, titrated to 900-1800 mg/day (max 3600) - renal dose adjustment
- Pregabalin 75 mg bd, titrated - misuse and diversion are real; pregabalin is now a monitored medicine in Australian real-time prescription monitoring
- Switch to another first-line agent if one fails; combine only if monotherapy at adequate dose and duration fails (OPTION-DM)
- Trigeminal neuralgia is the exception - carbamazepine first-line
- Topical: capsaicin 8% patch, lidocaine 5% patch for localised pain
- *Opioids are not first-line and should generally be avoided; there is no role for NSAIDs or paracetamol in true neuropathic pain*
C. Protect the insensate part - the bit that is always forgotten
- Daily foot inspection, well-fitted footwear, podiatry, no hot water bottles or heaters
- Falls prevention, home OT assessment, night lighting for sensory ataxia
- Driving assessment if proprioception is impaired
- Physiotherapy, balance retraining; exercise has the best evidence of any intervention for symptoms and function
Traps
- *A normal nerve conduction study does not exclude neuropathy* - it is blind to small fibres. Skin biopsy or QST is the test
- Test pinprick and vibration separately - dissociated loss is the single most localising finding, and it is invisible if you only test light touch
- The cord level is usually 1-2 segments ABOVE the clinical sensory level - image generously
- Crossed sensory loss (ipsilateral face, contralateral body) = lateral medulla, not a hemisphere lesion
- Brown-Sequard: dorsal column loss IPSILATERAL, spinothalamic loss CONTRALATERAL and 1-2 levels below
- *Never give folate before B12* - it precipitates or worsens subacute combined degeneration
- A "normal" serum B12 does not exclude deficiency - check active B12, homocysteine and methylmalonic acid, especially with nitrous oxide use
- Steroids and IVIg both work in CIDP, but steroids make multifocal motor neuropathy worse
- Mononeuritis multiplex is vasculitis until proven otherwise - it needs urgent immunosuppression, not a nerve conduction study next month
- Bilateral carpal tunnel syndrome in a man over 60 with cardiac symptoms = think ATTR amyloidosis**
- Do not blame diabetes for an asymmetric, rapidly progressive, or predominantly motor neuropathy - look further
- Functional sensory loss is diagnosed on positive signs (exact midline splitting, vibration stopping at the sternum, inconsistency on distraction) - and it is a diagnosis, not an accusation
- Chemotherapy neuropathy is dose-limiting: report it early - the deficit may not reverse
Talk track
1. Localise before you list causes
- "I'd approach this anatomically - is the lesion in the brain, cord, root, plexus, peripheral nerve or small fibre? The distribution and the modalities involved tell me that before I think about aetiology."
2. The pattern that decides it
- "I test pinprick and temperature separately from vibration and joint position sense. Dissociated loss points me to the cord - spinothalamic loss alone to a central or anterior cord lesion, dorsal column loss alone to subacute combined degeneration or a posterior column process."
3. What I would not miss
- "A sensory level with bladder involvement is cord compression until I've imaged the whole spine, and saddle anaesthesia with bilateral sciatica is a cauda equina syndrome that gets an MRI today."
4. The reversible causes
- "Then I actively look for what's treatable - B12 including nitrous oxide use, a paraprotein, thyroid, diabetes, alcohol, drugs, and vasculitis - because mononeuritis multiplex is vasculitis until proven otherwise."
5. Investigation with a purpose
- "Nerve conduction studies answer whether it's axonal or demyelinating and whether it's symmetric or multifocal, which reorders the differential completely. And I'd remember a normal study doesn't exclude a small-fibre neuropathy."
6. Close on function
- "Then the practical consequences - foot care and ulcer prevention, falls risk, driving, and a realistic conversation about neuropathic pain, where I'd aim for a meaningful reduction rather than abolition."
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