Motor neurone disease

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

MND is a group of progressive neurodegenerative motor syndromes. Amyotrophic lateral sclerosis combines upper and lower motor neurone involvement; progressive muscular atrophy is lower-motor-predominant and primary lateral sclerosis upper-motor-predominant; progressive bulbar palsy begins with speech and swallowing. Symptoms include focal hand wasting, foot drop, cramps, fasciculation, stiffness, loss of dexterity, slurred speech, choking and breathlessness. Eye movements, sensation and bladder function are often preserved until late, so prominent sensory loss, early sphincter dysfunction, fluctuating fatigability or ocular weakness should redirect the differential. Mimics include cervical myelopathy, multifocal motor neuropathy, myasthenia, inclusion-body myositis, Kennedy disease, thyroid or B12 disorders and structural lesions.

Diagnosis is clinical and supported by EMG evidence of active and chronic denervation across regions. MRI brain or spine excludes structural disease, and bloods address metabolic, inflammatory, infectious and paraprotein mimics. Genetic testing is increasingly relevant, especially with family history, frontotemporal features or young onset, and requires counselling because penetrance and implications vary. Do not delay referral until every region shows both upper and lower motor signs. At diagnosis introduce the multidisciplinary team: neurology, specialist nursing, respiratory, speech and language, dietetics, physiotherapy, occupational therapy, psychology, palliative care, gastroenterology and social services. Provide information at the person's pace and identify how they wish difficult updates communicated.

Care anticipates predictable losses. Respiratory review includes symptoms, cough and FVC or VC with SNIP or maximal inspiratory pressure; bulbar weakness can make mouthpiece tests unreliable. Nocturnal oximetry plus transcutaneous CO2 or sleep study may clarify early hypoventilation. Offer NIV when symptoms and tests indicate, with cough augmentation, suction and secretion plans. Speech therapy should introduce voice banking and communication technology before speech becomes unusable. Monitor weight and mealtime burden and discuss gastrostomy before marked respiratory compromise. Riluzole is offered for ALS; it modestly extends survival but does not restore power. Treat sialorrhoea, thick secretions, cramps, spasticity, pain and emotional lability individually. Discuss driving, work, benefits, lasting powers, advance decisions, ventilation withdrawal preferences and preferred place of care without implying that palliative involvement means abandonment.

Key points

Motor neurone disease causes progressive motor weakness with upper motor neurone signs, lower motor neurone signs or both, usually without sensory loss or sphincter disturbance.
Lower motor neurone findings are wasting, fasciculation and weakness with reduced reflexes; upper motor neurone findings include spasticity, brisk reflexes, clonus and extensor plantar responses.
Presentation may be limb onset, bulbar onset with dysarthria or dysphagia, or less commonly respiratory onset; persistent isolated symptoms still need mimic exclusion.
Refer suspected MND without delay to a neurologist and then a coordinated multidisciplinary team; repeated musculoskeletal treatment can waste crucial planning time.
Assess cognition and behaviour because frontotemporal executive or language change affects communication, capacity, adherence and family support.
Offer riluzole for amyotrophic lateral sclerosis according to NICE, discussing modest survival benefit and liver and haematological monitoring rather than promising symptom improvement.
Monitor forced vital capacity or vital capacity plus SNIP or maximal inspiratory pressure and symptoms every 2–3 months or sooner when decline accelerates.
Non-invasive ventilation can improve quality of life and survival; discuss it before crisis, adapt interfaces and communication and clarify that oxygen alone can worsen unrecognised hypoventilation.
Discuss gastrostomy early while swallowing, respiratory reserve and decision-making allow choice; waiting for severe weight loss or aspiration increases procedural risk.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Sporadic neurodegeneration

Most MND arises without an identifiable single cause through interacting age-related, cellular and genetic susceptibility affecting motor neurons.

Inherited motor-neurone disease

Pathogenic variants including C9orf72, SOD1 and other genes cause familial or apparently sporadic disease and may guide counselling or targeted treatment eligibility.

Frontotemporal overlap

Shared genetic and protein biology links MND with frontotemporal degeneration, producing executive, behavioural or language change in a clinically important subgroup.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Protein and cellular dysfunction
Abnormal protein handling, RNA processing, mitochondrial stress and impaired axonal transport disrupt vulnerable upper and lower motor neurons.
2
Motor-neuron degeneration
Loss of corticospinal neurons causes spasticity and brisk reflexes, while anterior-horn and bulbar motor-neuron loss causes weakness, wasting and fasciculation.
3
Progressive network spread
Degeneration extends between limb, bulbar and respiratory motor systems, steadily reducing voluntary movement while sensation is usually preserved.
4
Ventilatory and bulbar failure
Diaphragmatic, cough and swallowing weakness cause hypoventilation, secretion retention, aspiration and nutritional decline as disease progresses.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Mixed motor signsRed flag

Focal wasting and fasciculation alongside brisk reflexes, spasticity or extensor plantars in progressive weakness strongly suggests combined motor neurone degeneration.

Bulbar onsetRed flag

Progressive slurred or nasal speech, weak tongue with fasciculation, choking and emotional lability can precede obvious limb weakness.

Respiratory onsetRed flag

Orthopnoea, morning headache, unrefreshing sleep, weak cough and daytime somnolence with preserved lungs can reflect diaphragmatic and respiratory muscle weakness.

Frontotemporal overlap

Apathy, disinhibition, rigid behaviour, loss of empathy, executive dysfunction or language change can accompany MND and affect safety and decisions.

Communication vulnerability

Severe dysarthria may conceal intact cognition and capacity; provide eye-gaze, alphabet or electronic communication before interpreting silence as inability.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Neurological examination across regionsFirst step
Why
Demonstrate progressive upper and lower motor neurone involvement and identify sensory, ocular or sphincter clues to mimics.
Interpretation and limitations
Concordant bulbar, cervical, thoracic and lumbosacral signs increase diagnostic confidence; absence of one sign early does not justify prolonged delay.
02
EMG and nerve-conduction studies
Why
Show active and chronic denervation and exclude conduction block, diffuse sensory neuropathy or neuromuscular junction disease.
Interpretation and limitations
EMG samples several regions and supports but does not replace clinical progression; conduction block suggests potentially treatable multifocal motor neuropathy.
03
MRI brain and spine
Why
Exclude cord compression, tumour, inflammatory disease, stroke and other structural explanations for the motor syndrome.
Interpretation and limitations
Common degenerative changes must match the distribution; incidental cervical disease should not explain bulbar or widespread lower motor findings falsely.
04
Mimic blood screen
Why
Assess thyroid, B12 or folate, calcium, CK, inflammatory, paraprotein, infection and other history-led reversible causes.
Interpretation and limitations
Mild CK elevation can occur from denervation; a major rise or clear myopathic pattern shifts assessment towards muscle disease.
05
Respiratory function assessment
Why
Measure ventilatory and cough reserve before symptoms become a crisis and guide NIV timing.
Interpretation and limitations
Use FVC or VC plus SNIP or maximal inspiratory pressure, symptoms and trajectory; normal oxygen saturation alone is inadequate.
06
Genetic counselling and testing
Why
Identify an inherited MND-FTD cause where results aid diagnosis, family advice or treatment eligibility.
Interpretation and limitations
Consent must cover uncertain penetrance and relatives; testing an affected person is distinct from predictive testing in an unaffected family member.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Cervical myelopathy

Sensory symptoms, sphincter change and concordant cord compression favour myelopathy; mixed upper and lower motor signs can otherwise closely resemble MND.

Multifocal motor neuropathy

Asymmetric lower motor-neurone weakness with conduction block and no upper motor-neurone signs supports a treatable immune neuropathy.

Myasthenia or myopathy

Fatigable ocular-bulbar weakness suggests junctional disease, while proximal weakness with muscle enzyme or myopathic findings supports muscle disease.

Functional weakness

Positive inconsistency and preserved automatic strength support FND; progressive atrophy, fasciculation and denervation indicate motor-neuron loss.

Additional chapter-specific clues

Mimic featureRed flag

Prominent numbness, a sensory level, sphincter dysfunction, fluctuating ptosis or pain-dominant weakness should prompt investigation for neuropathy, cord disease or junction disorder.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01SuspectRefer progressive motor dysfunction earlyFirst stepFocal weakness, wasting, fasciculation, spasticity or bulbar dysfunction progresses without a sensory explanation.

1Map upper and lower motor signs across regions, document progression and ask about speech, swallowing, breathing, cognition, sensation and sphincters.
2Arrange urgent neurology referral and targeted EMG, imaging and mimic bloods rather than requiring textbook-complete ALS before specialist review.
3Assess nutrition, cough, supine breathing and communication immediately because supportive needs can predate diagnostic certainty.
4On diagnosis link the person and family to the MND multidisciplinary team and provide a named route for rapid change.

02RespiratoryOffer support before emergency ventilationSymptoms or serial respiratory tests show declining ventilatory or cough reserve.

1Review orthopnoea, sleep, morning headache, somnolence, chest infections, cough and secretion handling with FVC or VC and SNIP or pressure measures.
2Use overnight oximetry with CO2 assessment or specialist sleep testing when daytime measures and symptoms are discordant.
3Discuss and trial NIV with interface, humidification, communication and carer support, adding cough augmentation or suction as needed.
4Create an emergency plan and discuss future invasive ventilation and possible NIV withdrawal preferences before communication or capacity deteriorates.

03Anticipatory carePreserve nutrition, communication and choiceBulbar, limb or cognitive progression begins to alter daily life.

1Introduce communication aids and voice banking early, assess swallowing and meal duration and monitor weight at each multidisciplinary review.
2Discuss gastrostomy while respiratory reserve and participation permit safer informed choice, without framing tube feeding as obligatory.
3Treat saliva, secretions, spasticity, cramps, pain and emotional lability with target-specific trials and therapy input.
4PreferredReview work, driving, equipment, home care, advance decisions, lasting powers and preferred place of care at the person's chosen pace.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

NICE recommends riluzole to extend survival for amyotrophic lateral sclerosis; it is not expected to restore lost muscle strength.

Riluzole

50 mg orally twice daily, taken consistently in relation to food according to the current product information and specialist prescription.

Monitor liver enzymes and blood count under the specialist schedule; nausea, fatigue and rare neutropenia or hepatic injury require review and interacting hepatotoxic drugs matter.

Reduces troublesome thin saliva and aspiration or communication burden in selected people with bulbar dysfunction.

Glycopyrronium bromide for sialorrhoea

Use a low oral or enteral specialist dose and titrate against drooling, secretion thickness and anticholinergic adverse effects.

Can thicken secretions, dry the mouth, worsen constipation or retention and make airway clearance harder; pair with cough and secretion assessment.

Can reduce painful spasticity and spasms when upper motor neurone features impair care or mobility.

Baclofen for spasticity

Start at a low dose, often 5 mg three times daily, and titrate slowly to comfort and function under specialist review.

Weakness, sedation and respiratory effects may worsen function; renal adjustment and gradual withdrawal are essential, and tone may sometimes aid transfers.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Respiratory failure

Progressive inspiratory and expiratory weakness causes nocturnal then daytime hypoventilation, infection and life-threatening ventilatory failure over time.

Dysphagia and malnutrition

Bulbar weakness causes prolonged meals, aspiration, dehydration and weight loss, reducing resilience and complicating later feeding procedures.

Communication loss

Dysarthria and limb weakness can remove speech, writing and device access unless augmentative communication is introduced early.

Immobility and cognitive burden

Weakness causes falls, pressure injury, pain and dependence, while frontotemporal change can complicate capacity, adherence and family coping.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

NICE advises multidisciplinary review usually every 2–3 months, sooner with rapid change, covering motor, bulbar, respiratory, cognitive and social domains.
Trend FVC or VC, SNIP or maximal inspiratory pressure, cough effectiveness, orthopnoea, sleep and morning symptoms rather than pulse oximetry alone.
Measure weight, meal duration, choking, hydration and communication and revisit gastrostomy and augmentative communication before crisis.
During riluzole follow specialist liver and blood monitoring and ask about nausea, fatigue, infection and new jaundice or dark urine.
Review equipment, falls, pressure care, pain, saliva, bowel function, mood, carer strain, benefits and home adaptations at each team contact.
Revisit advance decisions and ventilation preferences when the person wishes or clinical options change, verifying communication and decision-specific capacity.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Fasciculation needs context

Visible twitches occur benignly, but fasciculation with progressive weakness, wasting and abnormal reflexes is a different clinical signal.

Dysarthria is not incapacity

Motor speech failure can coexist with intact understanding; accessible communication is a prerequisite before assessing consent or cognition.

Saturation misses ventilation

Neuromuscular carbon-dioxide retention can evolve with apparently acceptable oxygen saturation, and unmonitored oxygen may worsen hypercapnia.

Gastrostomy timing is risk management

Early discussion preserves choice and allows safer placement; it does not force a procedure and can be revisited as values and function change.

Palliative and active care coexist

Symptom control, NIV, communication technology and advance planning all improve active living and are not mutually exclusive with life-prolonging treatment.

11Common pitfallsFrequent interpretation and management errors.

01
Waiting for every limb to show both upper and lower motor signs before referring a clearly progressive motor syndrome.
02
Attributing hand wasting to cervical degeneration despite bulbar signs, widespread fasciculation or progression beyond one anatomical level.
03
Using normal resting oxygen saturation to reassure about orthopnoea, weak cough and morning headache without respiratory mechanics or CO2 assessment.
04
Discussing communication aids, gastrostomy or NIV only after speech, nutrition or respiratory reserve has severely deteriorated.
05
Presenting riluzole as a symptomatic cure rather than a modest disease-modifying option requiring liver and blood monitoring.
06
Assuming severe dysarthria means cognitive incapacity and excluding the person from decisions before providing an accessible communication method.