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Motor Neurone Disease / ALS — Long-Term Management

Registrar reference · NICE NG42 · EAN · Gold Coast criteria
Compiled Jun 2026
Verify doses & access
Care > drugs
Decision support only — MND is managed by neurology and a multidisciplinary team, and the framing here is deliberately honest: the interventions that extend survival are the clinic, ventilation and nutrition, not the drugs, which are marginal. Exclude the one genuinely treatable mimic (multifocal motor neuropathy) before settling the diagnosis. Median survival is 2–3 years from onset but the spread is wide. Verify all doses and current access.
1 What actually changes survival
Multidisciplinary clinicstrongest lever
Everyone, from diagnosis.
Attendance at a specialist MND multidisciplinary clinic extends survival and improves quality of life — a larger effect than any drug. Neurology, respiratory, dietitian, speech, OT/PT, palliative care, MND nurse.
Non-invasive ventilationsurvival + QoL
Respiratory muscle failure develops.
NIV improves survival and sustains quality of life Bourke — median gain ~7 months, largest with preserved bulbar function. Start at the first sign of hypoventilation, not late.
Riluzolemodest
All, unless contraindicated.
Riluzole 50 mg bd prolongs survival ~2–3 months (Cochrane). The mainstay drug, but be honest with patients about the size of the effect. Monitor LFTs.
Gastrostomy + nutritiontiming matters
Dysphagia or weight loss.
Maintains weight and hydration; place before FVC falls too low (safer >50% predicted; RIG if FVC low). Weight loss is a poor prognostic sign.
Precision option: tofersen (intrathecal) for the ~2% with SOD1-ALS VALOR. Marginal or gone: edaravone (small subgroup benefit, not funded here); AMX0035/Relyvrio withdrawn in 2024 after the PHOENIX phase 3 failed despite a positive phase 2 CENTAUR. Harmful: diaphragm pacing worsened survival DiPALS. Everything in §5 is symptom control — it transforms quality of life without extending it.
2 Diagnose it — and exclude the treatable mimic

The pattern & the phenotypes

  • CoreProgressive, painless weakness with upper and lower motor neurone signs in the same regions; fasciculations, wasting, spasticity, brisk reflexes. No sensory loss, no early sphincter involvement — if present, doubt the diagnosis.
  • PhenotypesALS (UMN+LMN); PLS (UMN only, slow); PMA (LMN only); progressive bulbar palsy (speech/swallow onset, worse prognosis).
  • CriteriaGold Coast criteria (2020) simplified diagnosis: progressive motor impairment + UMN and LMN dysfunction in ≥1 region (or LMN in ≥2), with other causes excluded.
  • DelayDiagnosis is typically 10–16 months late — a real problem, since the levers above work better earlier.

Before you commit to the label

  • MMNMultifocal motor neuropathy is the mimic you cannot miss — pure LMN, conduction block on NCS, anti-GM1, and it responds to IVIg. Treatable.
  • OthersCervical/lumbar spondylotic myelo-radiculopathy, Kennedy disease (SBMA), inclusion body myositis, CIDP, myasthenia, thyrotoxicosis, paraneoplastic.
  • GeneticsC9orf72 (commonest familial, links to FTD), SOD1, TARDBP, FUS. ~10% familial; offer genetic counselling, and SOD1 testing matters now it is actionable (tofersen).
  • CognitionUp to half have cognitive/behavioural change; ~15% meet FTD criteria (§6). Neurofilament light is a supportive/prognostic biomarker.
3 Disease-modifying therapy — the honest picture

What to offer

  • Riluzole50 mg bd, glutamate modulator; ~2–3 month survival gain; LFT monitoring. Offer to everyone who wants it.
  • TofersenIntrathecal antisense oligonucleotide for SOD1-ALS only; VALOR missed its primary endpoint but lowered neurofilament, and open-label data support use; FDA accelerated approval 2023.
  • EdaravoneFree-radical scavenger; benefit confined to an early, faster-progressing subgroup; not funded in Australia/UK/EU on current evidence.

Read the evidence critically

  • AMX0035A cautionary tale: CENTAUR (phase 2) looked positive, PHOENIX (phase 3, 2024) was negative, and the drug was withdrawn. Small early trials in ALS mislead.
  • ConfoundingObservational "riluzole works better than the trials show" studies are confounded — riluzole users also get MDT care and NIV.
  • FramingThe drugs slow, they don't stop. The honest conversation names the modest size and directs energy to the clinic, breathing and nutrition.
4 Respiratory — monitor early, ventilate early

Monitoring

  • TestsFVC (sitting and supine) — a supine drop flags diaphragm weakness; SNIP (sniff nasal inspiratory pressure); overnight oximetry ± capnography.
  • SymptomsOrthopnoea, morning headache, unrefreshing sleep, daytime somnolence — hypoventilation before the numbers collapse.
  • PrognosisRespiratory failure is the usual cause of death; once FVC <50% predicted, mortality climbs steeply.

Interventions

  • NIVStart at the first hypoventilation (orthopnoea + reduced inspiratory pressure, or symptomatic hypercapnia) — survival and QoL benefit (§1).
  • SecretionsMechanical insufflation-exsufflation (cough assist) for weak cough; suction; treat sialorrhoea (§5) and thick secretions (carbocisteine, hydration).
  • Don'tDiaphragm pacing worsens survival — do not use DiPALS.
  • TracheostomyInvasive ventilation prolongs life but with high burden and dependency; rarely chosen, and only after explicit informed discussion.
5 Symptom control — where quality of life is won

Bulbar & secretions

  • SialorrhoeaAmitriptyline, glycopyrrolate, hyoscine; botulinum toxin to salivary glands or gland radiotherapy if refractory.
  • Thick mucusHydration, carbocisteine, nebulised saline; a suction unit and cough assist.
  • PBAPseudobulbar affect → dextromethorphan-quinidine, or an SSRI/amitriptyline.

Motor & comfort

  • SpasticityBaclofen, tizanidine; physio for contracture prevention.
  • CrampsMexiletine has trial evidence; stretching; quinine is a last resort.
  • PainMusculoskeletal from immobility/weak muscles → analgesia, positioning, PT.

Function & mood

  • CommunicationBank the voice early; speech-generating devices, eye-gaze tech as speech fails.
  • MobilityOT/PT, aids, wheelchair, home modification — stay ahead of the decline.
  • Mood/sleepDepression, anxiety and insomnia are common and treatable; ask.
6 Cognition, capacity & caregivers

The ALS–FTD spectrum

  • ScreenUse the ECAS (Edinburgh Cognitive and Behavioural ALS Screen) — designed for motor disability. Cognitive/behavioural change is common; frank FTD in ~15%, often C9orf72.
  • Why it mattersBehavioural variant FTD affects capacity, adherence and advance-care decisions — and it changes the family's experience. Identify it before the big conversations.

The caregiver

  • BurdenCaregiver strain is heavy and predicts poor outcomes for both. Assess and support it directly — respite, psychology, MND association services.
  • CoordinationThe MND nurse/care coordinator holds the plan together between clinic visits.
7 Advance care planning & the end of life

Plan early, revisit often

  • TimingStart advance care planning early, while communication and cognition are intact — decisions about NIV limits, tracheostomy, gastrostomy, resuscitation and place of care.
  • PalliativeInvolve palliative care early, not as a final referral; it improves quality of life alongside active management.
  • TrackingALSFRS-R quantifies functional decline and frames prognosis over time.

The terminal phase

  • DyspnoeaAnticipatory opioids and benzodiazepines relieve breathlessness and distress at the end; plan for NIV withdrawal if the patient chooses to stop.
  • FearPatients fear "choking to death" — reassure that a well-managed respiratory death is peaceful with anticipatory medication.
  • VADVoluntary assisted dying is lawful in Victoria (and all Australian states); MND is a common qualifying condition. Respond openly if raised, and know the referral pathway.
Guidelines. NICE NG42 (motor neurone disease: assessment and management); EAN guideline on ALS management; Gold Coast diagnostic criteria (Shefner 2020); MND Australia.   Trials & reviews. Bensimon (NEJM 1994) & Lacomblez (Lancet 1996) riluzole; Cochrane riluzole review (~2–3 month survival); Bourke NIV RCT (Lancet Neurology 2006 — survival + QoL); DiPALS diaphragm pacing (Lancet Neurology 2015 — harmful); edaravone (Lancet Neurology 2017 subgroup); VALOR tofersen for SOD1 (NEJM 2022); CENTAUR (AMX0035, phase 2) → PHOENIX (phase 3 negative, 2024 — drug withdrawn); Brown & Al-Chalabi ALS review (NEJM 2017); "New developments in diagnosis and management of MND," Br Med Bull 2024.   Caveats. The survival evidence sits with multidisciplinary care, NIV and nutrition; drug effects are modest and, for AMX0035, reversed on phase 3. Exclude multifocal motor neuropathy (IVIg-responsive) before diagnosing MND. Prognosis is heterogeneous — PLS is slow, bulbar and respiratory-onset are fast, C9orf72 tends faster. Access to tofersen/edaravone is region-specific; confirm locally. Verify all doses. Companion to the neurology set (stroke, seizures, migraine, Parkinson's, MS).