📋 Key Information Summary
- Upper motor neurone (UMN) lesions produce spastic weakness with hyperreflexia and upgoing plantars; lower motor neurone (LMN) lesions cause flaccid weakness with hyporeflexia and fasciculation — localising the lesion level is the first critical step in every weak patient.
- Neurogenic vs myogenic weakness is distinguished by pattern of involvement (proximal vs distal), CK, EMG/NCS, and when needed muscle biopsy — CK >5× normal with myalgia demands urgent assessment for rhabdomyolysis.
- Essential tremor is the most common tremor in general practice (postural ± kinetic, bilateral, family history positive); Parkinsonian tremor is resting, asymmetric, and accompanied by bradykinesia and rigidity.
- Multiple sclerosis (MS) — Australian prevalence ≈ 33 000; MRI brain/spine with gadolinium is the cornerstone investigation; disease-modifying therapies (DMTs) require neurologist initiation and authority PBS prescribing.
- Myasthenia gravis (MG) — fatigable weakness (ptosis, diplopia, bulbar symptoms), anti-AChR antibodies positive in ~85%, ice-pack test is a useful bedside screening tool; acetylcholinesterase inhibitors are first-line symptomatic therapy.
- Motor neurone disease (MND) — progressive UMN + LMN signs without sensory loss; median survival 2–3 years; riluzole (PBS Authority Required) extends survival by ≈3 months; early multidisciplinary care is essential.
- Peripheral neuropathy — commonest cause in Australia is diabetes mellitus; glove-and-stocking sensory loss ± weakness; nerve conduction studies differentiate demyelinating from axonal subtypes.
- Wernicke encephalopathy (WE) is a medical emergency — give IV thiamine 300–500 mg immediately on clinical suspicion; do NOT wait for confirmatory tests; the classic triad (confusion, ataxia, ophthalmoplegia) is present in only ~16% of cases.
- Any acute onset focal neurological deficit must be treated as stroke until proven otherwise — activate the stroke pathway and aim for CT brain within 20 minutes of arrival.
- Red-flag features requiring same-day specialist referral or emergency presentation: rapidly progressive weakness, respiratory compromise, new-onset bilateral leg weakness, suspected myasthenic or cholinergic crisis, and signs of raised intracranial pressure.
- Aboriginal and Torres Strait Islander Australians experience higher rates of diabetic neuropathy, stroke, and delayed access to neurology services — culturally safe care and remote telehealth pathways are critical to closing the gap.
- Thiamine deficiency is common in chronic alcohol use, bariatric surgery, hyperemesis gravidarum, and prolonged TPN — prescribe thiamine replacement empirically in all at-risk patients before glucose administration.
Introduction & Australian Epidemiology
Neurological complaints account for an estimated 10–20% of general practice consultations in Australia. Patients frequently present with non-specific symptoms — weakness, tremor, diplopia, or sensory disturbance — that challenge diagnosticians to localise the lesion (central vs peripheral, nerve vs muscle), identify the underlying aetiology, and initiate time-critical management. This article provides an Australian-focused, evidence-based framework for evaluating and managing the most common neurological dilemmas encountered in primary care.
Key Australian epidemiological data:
- Stroke: ~56 000 new or recurrent strokes per year; leading cause of adult disability (AIHW 2023).
- Multiple sclerosis: ~33 000 Australians living with MS; highest prevalence in Tasmania and south-eastern mainland states; female-to-male ratio ≈3:1 (MS Australia).
- Myasthenia gravis: prevalence ≈ 20–50 per 100 000; can occur at any age, peaks in women aged 20–40 and men aged 50–70.
- Motor neurone disease: ~2 000 Australians diagnosed annually; lifetime risk ≈1 in 300 (MND Australia).
- Diabetic peripheral neuropathy: affects up to 50% of people with type 2 diabetes over their lifetime (Baker IDI / Diabetes Australia).
- Wernicke encephalopathy: often unrecognised; autopsy studies suggest prevalence of 1–2% in the general population and up to 12–42% in chronic alcohol use cohorts.
Diagnostic anchoring risk: The most dangerous error in neurological diagnosis is premature closure — attributing new weakness to a known condition (e.g. diabetic neuropathy) when an alternative pathology (e.g. cord compression, stroke) is developing. Always reconsider the diagnosis when the clinical trajectory changes.
Motor Weakness — UMN vs LMN Lesions
The first step in evaluating any patient with weakness is to determine whether the lesion involves the upper motor neurone (UMN) pathway (cortex → brainstem → spinal cord) or the lower motor neurone (LMN) pathway (anterior horn cell → peripheral nerve → neuromuscular junction → muscle). This distinction guides all subsequent investigation and management.
Clinical Features: UMN vs LMN
| Feature | UMN Lesion | LMN Lesion |
|---|---|---|
| Tone | Spasticity (velocity-dependent ↑) | Flaccidity (↓) |
| Reflexes | Hyperreflexia; clonus | Hyporeflexia or absent |
| Plantar response | Extensor (Babinski positive) | Flexor or absent |
| Muscle bulk | Preserved (disuse atrophy late) | Atrophy (often early and focal) |
| Fasciculation | Absent | Present (especially MND) |
| Pattern | Pyramidal distribution (extensors in UL, flexors in LL) | Myotomal or peripheral nerve territory |
| Common causes | Stroke, MS, cord compression, MND | Radial nerve palsy, GBS, anterior horn cell disease, motor neuropathy |
Localising UMN Lesions
1
Brain (cortex/subcortex)
Contralateral weakness, often with cortical signs (aphasia if dominant hemisphere, neglect if non-dominant). Consider stroke, tumour, abscess.
2
Brainstem
Crossed signs (ipsilateral cranial nerve palsy + contralateral limb weakness). CN VI, VII, XII most commonly affected. Consider posterior fossa stroke, demyelination.
3
Spinal cord
Sensory level, bladder/bowel dysfunction, bilateral UMN signs below lesion. Distinguish complete from incomplete syndromes (Brown-Séquard, central cord, anterior cord).
Mixed UMN/LMN Patterns
The presence of both UMN and LMN signs in the same limb or region is a hallmark of motor neurone disease (MND/ALS) and should prompt urgent neurology referral. Other causes of mixed patterns include cervical spondylotic myelopathy with concurrent radiculopathy and combined system disease (vitamin B12 deficiency).
Cauda equina syndrome: Bilateral LMN leg weakness + saddle anaesthesia + urinary retention = surgical emergency. Requires urgent MRI and spinal surgical review within 24 hours. Do not delay for outpatient imaging.
Neurogenic vs Myogenic Muscle Weakness
Once UMN pathology has been excluded, the clinician must differentiate neurogenic (LMN / peripheral nerve / neuromuscular junction) weakness from myogenic (primary muscle disease) weakness. The pattern of weakness, associated features, and targeted investigations guide this distinction.
Distinguishing Features
| Feature | Neurogenic | Myogenic |
|---|---|---|
| Distribution | Distal predominant; follows nerve/root territory | Proximal predominant (shoulders, hips); symmetric |
| Reflexes | ↓ or absent early | Preserved until late/severe disease |
| Fasciculation | Often present (MND, radiculopathy) | Absent |
| CK | Normal or mildly ↑ | Often markedly ↑ (↑↑↑ in rhabdomyolysis, inflammatory myositis) |
| Myalgia | Usually absent | Common in inflammatory and metabolic myopathies |
| EMG pattern | Neurogenic motor unit changes (large, polyphasic); fibrillation potentials | Short-duration, low-amplitude, polyphasic units; early recruitment |
| NCS | Abnormal (conduction block, slowing, or reduced CMAP) | Normal motor and sensory conduction |
| Common aetiologies | Diabetic neuropathy, GBS, CIDP, CMT, radiculopathy, MND | Inflammatory myositis, statin myopathy, metabolic myopathy, muscular dystrophy |
Key Investigations in Primary Care
Essential
Creatine kinase (CK)
Markedly elevated CK (>5× ULN) suggests myopathy or rhabdomyolysis; levels >10 000 U/L with acute kidney injury require emergency management.
Essential
Nerve conduction studies / Electromyography (NCS/EMG)
Definitive test to differentiate neurogenic from myogenic pathology. Available at major hospitals; MBS Item 11012 (consultant neurologist). Wait times in regional areas may be 4–8 weeks.
Available
MRI muscle / MRI neurography
Identifies muscle oedema (inflammatory myositis), fatty infiltration (chronic myopathy), or nerve enlargement (CIDP, hereditary neuropathy).
Available
Muscle biopsy
Gold standard for inflammatory myositis and metabolic myopathies. Performed by surgeon; requires coordination with neuropathology. MBS Item 30062.
Available
Autoimmune panel (ANA, anti-Jo-1, anti-Mi-2, anti-SRP, anti-MDA5)
Specific autoantibodies define myositis subtypes and predict cancer-associated myositis risk.
Statin myopathy: Patients on statins (atorvastatin, rosuvastatin) presenting with proximal myalgia and elevated CK should have the statin ceased. CK >10× ULN or symptoms persisting beyond 2 weeks after cessation warrants neurology referral to exclude immune-mediated necrotising myopathy (anti-HMGCR antibodies).
Tremor
Tremor is the most common movement disorder encountered in general practice. The key diagnostic approach involves characterising the tremor type (resting, postural, kinetic, intention), distribution (unilateral vs bilateral), associated features, and age of onset.
Classification of Tremor
| Tremor Type | Characteristics | Frequency | Key Associations |
|---|---|---|---|
| Essential tremor (ET) | Postural ± kinetic; bilateral upper limbs; improves with alcohol; family history positive in ~50% | 4–12 Hz | Most common adult tremor; head tremor ("no-no" common); voice tremor |
| Parkinsonian tremor | Resting tremor; asymmetric onset; pill-rolling; suppressed with voluntary movement | 4–6 Hz | Bradykinesia + rigidity + postural instability; α-synucleinopathy |
| Dystonic tremor | Irregular, jerky; associated with dystonic posture; "geste antagoniste" (sensory trick reduces tremor) | Variable | Cervical dystonia, writer's cramp |
| Cerebellar / intention tremor | Low frequency; worsens towards target (finger–nose–finger); gait ataxia, nystagmus | 2–5 Hz | MS plaques, stroke, alcohol, medications (phenytoin) |
| Enhanced physiological tremor | Fine postural tremor; bilateral; exacerbated by anxiety, caffeine, thyrotoxicosis, medications | 8–12 Hz | β-agonists, lithium, valproate, caffeine, anxiety |
| Functional (psychogenic) tremor | Variable frequency; entrainable; distractible; onset abrupt; non-anatomical spread | Variable | Positive clinical features (Hoover sign); psychiatric comorbidity |
Essential Tremor — Pharmacological Management
Propranolol
Deralin® / Inderal® · Non-selective β-blocker
Adult dose
40 mg PO BD, titrate to 80–320 mg/day in divided doses (or long-acting 80–160 mg OM)
Paediatric dose
0.5–1 mg/kg/day PO in 2–3 divided doses (specialist initiation)
Renal / hepatic
No renal adjustment; caution in hepatic impairment (reduce dose)
PBS status
✔ PBS General Benefit
Primidone
Mysoline® · Anticonvulsant
Adult dose
Start 12.5–25 mg PO nocte, titrate slowly to 250–750 mg/day in 2–3 divided doses
Renal / hepatic
Reduce dose in renal impairment; contraindicated in severe hepatic disease
PBS status
✔ PBS General Benefit
Second-line for essential tremor: Gabapentin (titrate to 1200–3600 mg/day), topiramate (50–200 mg/day), or clonazepam (0.5–2 mg/day). Refractory cases may benefit from botulinum toxin injections (specialist) or deep brain stimulation (DBS) targeting the ventral intermediate nucleus of the thalamus.
Parkinsonian Tremor — When to Refer
Any patient with a resting tremor, bradykinesia (progressive slowness of movement with decrement and amplitude reduction on repetitive tasks), and rigidity should be referred to a general neurologist or movement disorder specialist for confirmation and initiation of dopaminergic therapy. In Australia, DaTSCAN (MBS Item 61408) may be used when the diagnosis is uncertain but is not required in clear clinical presentations.
Red flags in a tremor patient — refer urgently: Acute onset tremor (consider Wilson disease if <50 years, toxin, drug effect), unilateral progressive tremor with headache/vomiting (posterior fossa mass), new tremor with confusion and liver disease (hepatic encephalopathy, Wilson disease), and asterixis (flapping tremor of outstretched hands indicating metabolic encephalopathy).
Multiple Sclerosis (MS)
Multiple sclerosis is a chronic autoimmune demyelinating disease of the central nervous system and the most common cause of non-traumatic neurological disability in young Australian adults. Australia has one of the highest prevalence rates globally, with an estimated 33 000 people living with MS (MS Australia, 2023). The female-to-male ratio is approximately 3:1, and median age of onset is 30 years.
Clinical Subtypes
| Subtype | Frequency | Characteristics |
|---|---|---|
| Relapsing-remitting (RRMS) | ~85% at onset | Discrete relapses with full or partial recovery; stable between attacks |
| Secondary progressive (SPMS) | ~50% of RRMS within 15–20 yrs | Gradual worsening after initial RRMS course ± superimposed relapses |
| Primary progressive (PPMS) | ~10–15% | Steady decline from onset without distinct relapses; more common in men; later age onset |
Common Presenting Features
- Optic neuritis: Unilateral painful vision loss, relative afferent pupillary defect (RAPD); fundoscopy usually normal (retrobulbar). MRI shows optic nerve enhancement. 50% risk of MS within 15 years.
- Sensory symptoms: Paraesthesia, band-like tightness around trunk or limbs (Lhermitte sign — electric shock sensation on neck flexion suggests cervical cord plaque).
- Motor: UMN pattern weakness, spastic paraparesis.
- Cerebellar: Ataxia, intention tremor, scanning speech.
- Brainstem: Diplopia (internuclear ophthalmoplegia), facial numbness, vertigo, dysarthria.
- Bladder dysfunction: Urinary urgency, frequency, retention — very common and often under-reported.
Diagnostic Investigations
Essential
MRI brain and spine with gadolinium
Cornerstone of MS diagnosis. Demonstrates dissemination in space (≥1 T2 lesion in ≥2 of: periventricular, juxtacortical/cortical, infratentorial, spinal cord) and dissemination in time (simultaneous gadolinium-enhancing and non-enhancing lesions, or new T2 lesion on follow-up).
Essential
Lumbar puncture — CSF analysis
Oligoclonal bands (≥2 bands in CSF not present in serum) support diagnosis. Elevated IgG index. MBS Item 11012 performed in hospital or specialist rooms.
Available
Visual evoked potentials (VEP)
Prolonged P100 latency supports subclinical optic neuritis. Less commonly required since MRI availability improved.
Available
Serum neurofilament light chain (NfL)
Emerging biomarker for disease activity and treatment response; not yet routine in Australian practice but increasingly available through pathology services.
Acute Relapse Management
Methylprednisolone
Solu-Medrol® · Corticosteroid
Adult dose
1 g IV daily for 3–5 days (± oral prednisolone taper 1 mg/kg reducing over 2 weeks); some centres use 500 mg PO BD for 5 days as equivalent outpatient regimen
Renal / hepatic
No specific renal adjustment; caution in hepatic impairment and diabetes (hyperglycaemia risk)
PBS status
✔ PBS General Benefit (PO); ✔ PBS General Benefit (IV in hospital)
Disease-modifying therapies (DMTs): Over 15 DMTs are PBS-listed in Australia for relapsing MS, including injectable (interferon-β, glatiramer), oral (dimethyl fumarate, fingolimod, teriflunomide, cladribine, siponimod, ozanimod, ponesimod, diroximel fumarate), and infusion therapies (natalizumab, ocrelizumab, alemtuzumab). All require Authority Required PBS prescription initiated by a neurologist. Ocrelizumab is the only approved DMT for PPMS. Early DMT initiation (within the first clinical event meeting DIS + DIT criteria) improves long-term outcomes.
Myasthenia Gravis (MG)
Myasthenia gravis is an antibody-mediated autoimmune disorder of the neuromuscular characterised by fatigable weakness. In Australia, prevalence is approximately 20–50 per 100 000. The disease is classified by antibody type (anti-AChR ~85%, anti-MuSK ~5–8%, seronegative ~7%) and by clinical distribution (ocular, generalised, bulbar).
Clinical Features
- Ocular MG (≥50% present here): Ptosis (often asymmetric), diplopia — symptoms worse in evening and with sustained upgaze.
- Generalised MG: Proximal limb weakness, difficulty rising from chairs, dysphagia, dysarthria, nasal speech.
- Bulbar MG: Jaw fatigue with chewing, nasal regurgitation, aspiration risk.
- Key clinical sign: Fatigability — weakness worsens with repetitive use and improves with rest.
Bedside Tests
1
Ice-pack test
Apply ice pack over closed eye for 2 minutes. Improvement of ptosis by ≥2 mm is positive (sensitivity ~80%, specificity ~95%). Useful in ED and general practice.
2
Sustained upgaze
Ask patient to look upward for 60 seconds. Progressive ptosis or inability to maintain gaze suggests MG.
3
Fatigable weakness testing
Count to 50 or read aloud for 2 minutes — nasal voice, dysarthria, or voice fatigue may emerge. Shoulder abduction held for 60 seconds may demonstrate proximal fatigability.
Investigations
Essential
Anti-AChR antibodies (binding, blocking, modulating)
Positive in ~85% of generalised MG, ~50% of ocular MG. Available through major pathology labs (MBS Item 66515).
Essential
Anti-MuSK antibodies
Order if AChR-negative. Associated with prominent bulbar and facial weakness. May not respond well to cholinesterase inhibitors.
Available
CT chest / MRI mediastinum
Screen for thymoma in all newly diagnosed MG patients (present in ~10–15% of AChR-positive MG).
Available
Repetitive nerve stimulation (RNS) / Single-fibre EMG
Decremental response on RNS (≥10% decrement at 2–3 Hz stimulation). Single-fibre EMG is most sensitive test but requires specialist equipment and expertise.
Pharmacological Management
Pyridostigmine
Mestinon® · Acetylcholinesterase inhibitor
Adult dose
30–60 mg PO TDS–QID (max 120 mg per dose); onset 15–30 min, duration 3–4 h; long-acting 180 mg nocte available
Paediatric dose
7 mg/kg/day PO in 5–6 divided doses (neonatal/juvenile MG — specialist management)
Renal / hepatic
Use with caution; reduce dose in renal impairment; hepatic impairment — no specific guidelines, titrate to response
PBS status
⚠ PBS Authority Required
Myasthenic crisis: Acute respiratory failure from severe bulbar/respiratory muscle weakness. Peak inspiratory pressure (PiMax) <–20 cmH₂O or vital capacity <20 mL/kg warrants ICU admission, non-invasive or invasive ventilation, and urgent plasma exchange (PLEX) or IV immunoglobulin (IVIg 2 g/kg over 2–5 days). Avoid medications that worsen MG: aminoglycosides, fluoroquinolones, β-blockers, magnesium, D-penicillamine, neuromuscular blocking agents.
Long-term Immunosuppression (Specialist-Initiated)
Patients with generalised MG requiring ongoing immunosuppression are managed by neurologists. First-line steroid-sparing agent is azathioprine (PBS Authority Required). Mycophenolate mofetil, ciclosporin, and tacrolimus are second-line options. Rituximab is increasingly used for refractory MG, particularly MuSK-MG. Newer targeted therapies including eculizumab (anti-C5 complement inhibitor) and efgartigimod (anti-FcRn) are available for refractory AChR-positive generalised MG.
Motor Neurone Disease (MND)
Motor neurone disease (MND) — also known as amyotrophic lateral sclerosis (ALS) — is a progressive, fatal neurodegenerative disorder affecting both upper and lower motor neurones. Approximately 2 000 Australians are diagnosed annually, with a median survival of 2–3 years from symptom onset. There is no cure; management focuses on symptom control, maintaining quality of life, and multidisciplinary care.
Clinical Features — Overlapping UMN + LMN Signs
| Region | UMN Signs | LMN Signs |
|---|---|---|
| Bulbar | Spastic dysarthria, pseudobulbar affect (emotional lability) | Tongue fasciculation, atrophy, flaccid dysarthria |
| Upper limb | Spastic tone, hyperreflexia | Hand intrinsic wasting, fasciculation, grip weakness |
| Lower limb | Spastic paraparesis, upgoing plantars | Foot drop, wasting of anterior compartment |
| Respiratory | Spastic diaphragm (rare) | Diaphragm weakness — orthopnoea, morning headaches, daytime somnolence |
Mimics of MND — must be excluded: Cervical spondylotic myelopathy/radiculopathy (most common mimic; MRI cervical spine essential), multifocal motor neuropathy (treatable with IVIg; anti-GM1 antibodies), Kennedy disease (X-linked bulbar-spinal; gynaecomastia, sensory involvement), inclusion body myositis, and myasthenia gravis.
El Escorial / Awaji Diagnostic Criteria
Diagnosis requires evidence of UMN + LMN dysfunction in ≥2 body regions (bulbar, cervical, thoracic, lumbosacral), progression of symptoms, and exclusion of alternative diagnoses. EMG showing widespread denervation and reinnervation is supportive. Revised Awaji criteria allow fasciculation potentials to substitute for fibrillation potentials as evidence of active denervation.
Pharmacological Management
Riluzole
Rilutek® · Glutamate release inhibitor
Adult dose
50 mg PO BD (take 1 hour before or 2 hours after food)
Duration
Ongoing until disease progression or intolerance; extends median survival by approximately 2–3 months
Renal / hepatic
Contraindicated if ALT/AST >5× ULN; monitor LFTs monthly for 3 months then periodically; no renal adjustment
PBS status
🔒 PBS Authority Required (Specialist)
Edaravone
Radicava® · Free radical scavenger
Adult dose
60 mg IV infusion over 60 min; daily for 14 consecutive days, then 14 days off, then 10 of 14 days per cycle (28-day cycles)
Renal / hepatic
Caution in renal impairment; monitor hepatic function
PBS status
🔒 Not PBS-listed (access via Special Access Scheme or private prescription)
Symptomatic and Supportive Management
- Sialorrhoea: Glycopyrrolate 1 mg PO BD–TDS or hyoscine patch 1.5 mg/72 h; botulinum toxin injections to salivary glands (specialist).
- Pseudobulbar affect: Dextromethorphan/quinidine (Nuedexta®) — not PBS-listed; or SSRIs (off-label).
- Spasticity: Baclofen 5–20 mg PO TDS; tizanidine; botulinum toxin for focal spasticity.
- Cramps: Quinine sulfate (limited by TGA restrictions); magnesium; levetiracetam (limited evidence).
- Nutrition: Early dietitian involvement; percutaneous endoscopic gastrostomy (PEG) or radiologically inserted gastrostomy (RIG) when BMI declining or swallowing unsafe — ideally before FVC falls below 50% predicted.
- Respiratory: Non-invasive ventilation (NIV) when FVC <80% predicted or symptomatic nocturnal hypoventilation; referral to respiratory and sleep medicine; advance care planning including discussion of tracheostomy ventilation preferences.
- Multidisciplinary care: MND Australia care co-ordination; neurologist, respiratory physician, physiotherapist, occupational therapist, speech pathologist, dietitian, palliative care, social worker, and psychologist.
Peripheral Neuropathy
Peripheral neuropathy affects an estimated 2–8% of the general population and up to 50% of people with long-standing diabetes mellitus. The most common pattern is a length-dependent, sensorimotor, axonal polyneuropathy presenting with glove-and-stocking sensory loss. Accurate characterisation of the neuropathy pattern — distal vs proximal, axonal vs demyelinating, sensory vs motor — is essential for identifying treatable causes.
Classification by Pattern
| Pattern | Characteristics | Key Causes |
|---|---|---|
| Length-dependent (distal symmetric) | Stocking-glove sensory loss; distal weakness late | Diabetes, alcohol, B12 deficiency, chemotherapy, chronic kidney disease |
| Acute inflammatory demyelinating polyradiculoneuropathy (AIDP / GBS) | Acute ascending flaccid weakness + areflexia; may have respiratory involvement | Post-infectious (Campylobacter, CMV, EBV); treat with IVIg or PLEX |
| Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) | Progressive or relapsing proximal + distal weakness; areflexia; treatable | Autoimmune; IVIg, corticosteroids, plasma exchange |
| Mononeuritis multiplex | Multiple individual nerve territories affected sequentially | Vasculitis (granulomatosis with polyangiitis, PAN), diabetes, sarcoidosis, HIV, leprosy |
| Small fibre neuropathy | Burning pain, allodynia; normal NCS; preserved reflexes and motor function | Diabetes, idiopathic, Sjögren syndrome, celiac disease, Fabry disease |
Investigations — Tiered Approach
Tier 1 — First-line bloods (all patients)
- HbA1c / fasting glucose
- Vitamin B12, folate, methylmalonic acid
- FBC, ESR, CRP
- Renal function (eGFR), LFTs
- TFTs
- Serum protein electrophoresis + free light chains (screen for paraproteinaemia)
- Hepatitis B & C serology, HIV (if risk factors)
Tier 2 — Specialist-directed investigations
- Nerve conduction studies / EMG (MBS Item 11012)
- Anti-ganglioside antibodies (anti-GM1, anti-MAG)
- ANA, ANCA, anti-SSA/SSB (vasculitis, Sjögren)
- Nerve biopsy (sural nerve — vasculitis, amyloid)
- Skin punch biopsy for intraepidermal nerve fibre density (small fibre neuropathy)
- Genetic testing (CMT — PMP22 duplication, MFN2 mutations)
Neuropathic Pain Management
Pregabalin
Lyrica® · Gabapentinoid / α2δ ligand
Adult dose
Start 75 mg PO BD, titrate to 150–300 mg PO BD over 2–4 weeks; max 600 mg/day
Renal adjustment
eGFR 30–60: max 300 mg/day; eGFR 15–30: max 150 mg/day; eGFR <15: max 75 mg/day
PBS status
⚠ PBS Authority Required
Duloxetine
Cymbalta® · SNRI
Adult dose
30 mg PO daily for 1 week, then 60 mg PO daily; max 120 mg/day
Renal / hepatic
Avoid if eGFR <30; contraindicated in severe hepatic impairment
PBS status
⚠ PBS Authority Required
Guillain-Barré syndrome (GBS): Acute ascending weakness + areflexia following a viral illness is a neurological emergency. Refer immediately to hospital. Spirometry every 4–6 hours if bulbar/respiratory weakness present. First-line treatment is IVIg 0.4 g/kg/day for 5 days (PBS Authority Required in hospital). Plasma exchange is equally effective but less available. Corticosteroids are not effective in GBS.
Wernicke Encephalopathy
Wernicke encephalopathy (WE) is an acute, reversible condition caused by thiamine (vitamin B1) deficiency. If untreated, it progresses to Korsakoff syndrome — a chronic amnestic disorder with devastating functional consequences. WE remains significantly under-diagnosed in Australian hospitals; autopsy studies suggest that clinical diagnosis captures only 16–20% of cases (Harper et al.).
Clinical diagnosis — treat on suspicion: The classic triad of confusion, ataxia, and ophthalmoplegia is present in fewer than 16% of cases. Any patient with altered mental status + risk factors for thiamine deficiency should receive immediate IV thiamine. Do NOT wait for confirmatory tests. Do NOT give glucose before thiamine — glucose metabolism consumes remaining thiamine reserves and can precipitate or worsen Wernicke encephalopathy.
Caine Diagnostic Criteria (≥2 of 4 required)
1
Dietary deficiency
Chronic alcohol misuse, anorexia nervosa, bariatric surgery, prolonged vomiting (hyperemesis gravidarum), TPN without supplementation, prolonged fasting
2
Oculomotor abnormalities
Nystagmus (most common), bilateral lateral rectus palsy (CN VI), horizontal or combined gaze palsies; complete ophthalmoplegia is rare
3
Cerebellar dysfunction
Gait ataxia — broad-based, tandem gait failure; limb ataxia less common; may be masked by concurrent peripheral neuropathy
4
Altered mental state
Confusion, apathy, inattention, global disorientation; may mimic delirium from other causes
Thiamine Replacement — Emergency Protocol
Thiamine (Vitamin B1)
Benevit® IV · Water-soluble vitamin
Adult dose — suspected WE
300–500 mg IV in 100 mL normal saline over 30 minutes TDS for 3–5 days, then 250 mg IV/IM daily for a further 5 days or until clinical improvement; transition to 100 mg PO TDS ongoing
Prophylaxis dose (at-risk patients)
100 mg PO daily (or 100–300 mg IV if malabsorption suspected)
Route
IV is mandatory in acute WE — oral bioavailability is low and unreliable; IM is acceptable if IV access not immediately available
Renal / hepatic
No dose adjustment required — water-soluble vitamin, excess excreted renally
Safety
Anaphylaxis is rare but reported; administer in resuscitation-capable setting; observe for 30 min post-infusion
PBS status
✔ PBS General Benefit (IV and oral formulations)
Risk Factors Requiring Thiamine Prophylaxis
- Chronic alcohol use disorder (most common cause in Australia)
- Hyperemesis gravidarum
- Bariatric / gastrointestinal surgery (malabsorption)
- Prolonged nasogastric suction / total parenteral nutrition without B-vitamin supplementation
- Anorexia nervosa or prolonged fasting
- HIV/AIDS, malignancy (increased metabolic demand)
- Dialysis-dependent chronic kidney disease
Korsakoff syndrome: If Wernicke encephalopathy is not treated promptly, patients may develop irreversible anterograde amnesia, confabulation, and personality change. Up to 80% of patients who survive WE untreated progress to Korsakoff syndrome. Long-term residential care may be required.
Special Populations
Pregnancy
MS in pregnancy: Relapse risk decreases during pregnancy (especially 3rd trimester) but increases 3–6 months post-partum. Most DMTs must be ceased pre-conception (washout periods vary — teriflunomide requires cholestyramine washout; fingolimod must be stopped ≥2 months before conception due to rebound relapse risk). Glatiramer and interferon-β are considered lowest risk if DMT required during pregnancy. Alemtuzumab and cladribine have minimum 6-month washout.
Myasthenia gravis: May flare in the first trimester or post-partum. Pyridostigmine is safe in pregnancy. Neonatal transient MG (from transplacental AChR antibodies) occurs in ~10–20% of infants. Avoid magnesium sulfate for pre-eclampsia management — use alternative antihypertensives.
Hyperemesis gravidarum: High risk for Wernicke encephalopathy — prescribe thiamine 100 mg PO daily or IV if vomiting prevents oral intake.
Neuropathic pain: Pregabalin and gabapentin are generally avoided in pregnancy (limited safety data, potential teratogenicity). Amitriptyline is Category C. Discuss risk–benefit with specialist.
Paediatrics
Paediatric MS: ~3–5% of MS cases present before age 18. Higher relapse rate and greater lesion burden at onset. MRI protocols and DMT selection require specialist paediatric neurology input.
Juvenile MG: Predominantly ocular in children <12 years. Often seronegative. Pyridostigmine 7 mg/kg/day in divided doses. Thymectomy may be considered in generalised juvenile MG.
GBS in children: Rare but important; IVIg dosing is 2 g/kg total (divided over 2–5 days). Corticosteroids are not beneficial.
Charcot-Marie-Tooth disease: Most common inherited neuropathy in children; pes cavus, distal wasting, steppage gait. Genetic testing (PMP22 duplication) readily available. Supportive orthotics and physiotherapy.
Elderly
Diagnostic challenge: Elderly patients commonly have multimorbidity (diabetes, B12 deficiency, vascular disease) that may mask new neurological diagnoses. Low threshold for neuroimaging if new neurological signs develop.
Medication-related tremor: Review medications — valproate, lithium, β-agonists, SSRIs, and metoclopramide (tardive dyskinesia) are common culprits.
MS in older adults: PPMS is more common at later onset. Diagnostic workup must exclude compressive myelopathy, small vessel disease, and neuromyelitis optica spectrum disorder (NMOSD — anti-AQP4 antibodies).
Polypharmacy caution: Pyridostigmine and neuropathic pain medications (pregabalin, duloxetine) — start low, titrate slowly; increased fall risk.
Renal Impairment
Pregabalin: Significant renal clearance — mandatory dose reduction by eGFR (see peripheral neuropathy section above). Accumulation causes somnolence, oedema, and confusion.
Uraemic neuropathy: Distal sensorimotor polyneuropathy common in CKD stage 4–5. Often improves after renal transplantation.
Riluzole: No dose adjustment in renal impairment, but active metabolites may accumulate — monitor.
IVIg: Use with caution in renal impairment — sucrose-containing formulations are nephrotoxic; prefer non-sucrose IVIg preparations. Monitor creatinine during infusion.
Hepatic Impairment
Riluzole: Contraindicated if baseline ALT/AST >5× ULN. Monitor LFTs monthly for first 3 months.
Hepatic encephalopathy: Can mimic Wernicke encephalopathy; asterixis (flapping tremor) is characteristic. Treat underlying precipitant; lactulose + rifaximin.
Duloxetine: Contraindicated in severe hepatic impairment (Child-Pugh C); use with caution in moderate impairment.
Propranolol: High first-pass metabolism — increase dose interval or reduce dose in significant liver disease.
Immunocompromised
DMTs in MS: Natalizumab carries risk of progressive multifocal leukoencephalopathy (PML) — highest risk in JCV antibody-positive patients with prior immunosuppression and >2 years of natalizumab use. Fingolimod increases herpes zoster risk — consider shingrix vaccination pre-initiation.
HIV-associated neuropathy: Distal symmetric polyneuropathy is the most common neurological complication of HIV. Some antiretrovirals (d4T, ddI, ddC) are directly neurotoxic. CMV polyradiculopathy requires urgent IV ganciclovir.
Post-transplant neurotoxicity: Calcineurin inhibitors (tacrolimus, ciclosporin) may cause posterior reversible encephalopathy syndrome (PRES), tremor, or seizures. Monitor drug levels closely.
Aboriginal and Torres Strait Islander Health Considerations
Aboriginal and Torres Strait Islander Health
Neurological conditions disproportionately affect Aboriginal and Torres Strait Islander Australians due to higher prevalence of risk factors (diabetes, alcohol-related harm, rheumatic heart disease, rheumatic fever), later presentation, and barriers to specialist access. Culturally safe, trauma-informed care is essential in all encounters.
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