About This Page
This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- MND/ALS affects both upper and lower motor neurones — mixed UMN+LMN signs in the SAME limb is the hallmark
- NO sensory involvement, NO eye movement abnormality, NO sphincter disturbance early — these distinguish MND from mimics
- Median survival: 3–5 years from symptom onset (variable)
- Riluzole is the only licensed disease-modifying drug — extends survival by ~3 months
- Non-invasive ventilation (NIV) improves survival and quality of life in respiratory failure
Overview
Motor neurone disease (MND) is a progressive neurodegenerative disease affecting upper motor neurones (corticospinal tracts) and lower motor neurones (anterior horn cells of the spinal cord and brainstem motor nuclei). The most common form is amyotrophic lateral sclerosis (ALS, ~80%), which features combined UMN and LMN signs. Other variants include progressive bulbar palsy (PBP, ~10–20%), progressive muscular atrophy (PMA, purely LMN), and primary lateral sclerosis (PLS, purely UMN). Frontotemporal dementia (FTD) coexists in ~15% and cognitive/behavioural change occurs in up to 50%.
Epidemiology
MND has a UK incidence of approximately 2 per 100,000 per year, with a prevalence of ~7 per 100,000. Mean age at onset is 60–65 years. It is slightly more common in men (1.5:1). Most cases are sporadic; approximately 5–10% are familial (C9orf72 repeat expansion is the most common genetic cause in the UK). Risk factors include advancing age, male sex, smoking, and military service.
Clinical Features
Symptoms
Progressive asymmetric limb weakness — typically starts in one hand or foot
Wasting of small muscles of the hand (split hand sign — thenar > hypothenar wasting)
Fasciculations — visible muscle twitching (LMN sign)
Dysphagia: difficulty swallowing (bulbar onset)
Dysarthria: slurred or nasal speech
Breathlessness: diaphragmatic weakness — orthopnoea, morning headache from nocturnal hypoventilation
Muscle cramps
Emotional lability (pseudobulbar affect) — involuntary crying or laughing
Signs
Combined UMN + LMN signs in the same limb — the diagnostic hallmark
LMN signs: wasting, fasciculations, reduced reflexes, flaccid weakness
UMN signs: spasticity, hyperreflexia, upgoing plantars, clonus
Tongue fasciculations and wasting (bulbar LMN)
Brisk jaw jerk (bulbar UMN)
NO sensory loss, NO cerebellar signs, NO eye movement abnormality
Investigations
First-line
Electromyography (EMG) and nerve conduction studiesEMG shows widespread denervation (fibrillations, fasciculations, large motor unit potentials) with normal sensory nerve conduction. Supports diagnosis and excludes mimics
MRI brain and spinal cordTo exclude structural mimics: cervical myelopathy, spinal cord compression, MS, tumour
BloodsCK (mildly raised in MND), TFTs, B12, folate, calcium, glucose, protein electrophoresis — to exclude treatable mimics
Second-line
Respiratory function testsFVC (forced vital capacity) — baseline and serial monitoring. FVC <50% predicted indicates need for NIV discussion. SNIP (sniff nasal inspiratory pressure) and nocturnal oximetry
Lumbar punctureIf diagnosis uncertain — to exclude inflammatory conditions (CIDP, MS)
Specialist
Genetic testingC9orf72 repeat expansion, SOD1 — consider if family history of MND or FTD
1
Disease-modifying treatment
- Riluzole 50 mg BD — the only licensed disease-modifying drug. Extends survival by approximately 2–3 months. Monitor LFTs
- Start as early as possible after diagnosis
2
Respiratory management
- Serial FVC monitoring every 2–3 months
- Non-invasive ventilation (NIV) when FVC <50% or symptoms of respiratory failure — improves survival and quality of life
- Discuss respiratory management options early including views on invasive ventilation
3
Symptom management
- Dysphagia: SALT assessment, modified diet, PEG/RIG feeding tube when indicated
- Sialorrhoea (drooling): glycopyrronium, hyoscine patch, botulinum toxin
- Spasticity: baclofen, physiotherapy
- Pain: neuropathic pain agents, opioids for terminal phase
- Emotional lability: SSRI or dextromethorphan/quinidine
- Communication aids: referral to SALT and assistive technology
4
MDT and end-of-life care
- MDT assessment every 2–3 months: neurology, respiratory, SALT, dietetics, OT, physiotherapy, palliative care, psychology
- Advance care planning — discuss early while capacity retained: preferred place of death, views on PEG/NIV/invasive ventilation
- Palliative care involvement from diagnosis — not just end-of-life
- DVLA: must notify — individual assessment required
Complications
- Respiratory failure: The usual cause of death. NIV extends survival and improves quality of life
- Aspiration pneumonia: From bulbar dysfunction and dysphagia
- Malnutrition and weight loss: Dysphagia and hypermetabolism — PEG/RIG tube when indicated
- Frontotemporal dementia: Co-occurs in ~15% — behavioural variant most common. Cognitive change in up to 50%
- Depression and anxiety: Screen and treat — specialist psychological support
- Venous thromboembolism: Immobility — prophylaxis as appropriate
UKMLA Exam Tips
- 1Combined UMN + LMN signs in the SAME limb WITHOUT sensory involvement = think MND
- 2Fasciculations + wasting + brisk reflexes in the same limb = classic MND pattern
- 3Tongue fasciculations = bulbar MND. Brisk jaw jerk = UMN bulbar involvement
- 4NO sensory loss, NO eye movement abnormality, NO cerebellar signs — these EXCLUDE MND
- 5Riluzole extends survival by ~3 months — only licensed disease-modifying drug
- 6NIV for respiratory failure — discuss EARLY before crisis
- 7Progressive bulbar palsy: dysarthria + dysphagia predominate. Worst prognosis variant (~2 years)
practicetest your knowledge on motor neurone diseaseApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — neurology and beyond.
open q-bank regional clinical guidance
Motor Neurone Disease: guidance by region
Recommendations, thresholds and pathways can differ. Open the page written for the jurisdiction you need.