Amyotrophic lateral sclerosis (ALS): an animated, cited guide

This page needs JavaScript for its animations. The outline and key answers are below, and every claim in the full version carries a numbered citation.

Not medical advice. ALS Companion is an educational synthesis of published literature. It does not replace a clinician.

What is in it

What ALS is Who gets it, the numbers, and the ways it starts.
Upper and lower motor neurons Two neurons, two sets of signs, animated.
TDP-43 and what goes wrong A protein leaves the nucleus and clumps.
Genes: C9orf72, SOD1 and more Familial ALS, repeat expansions and genetic testing.
Diagnosis and criteria The Gold Coast, revised El Escorial and Awaji criteria, as a calculator.
The differential Conditions that can look like ALS, and how they differ.
ALSFRS-R and the course The 12-item scale, the progression rate and the stages.
Riluzole, edaravone and others What each drug targets and what the trials found.
Tofersen An antisense drug that lowers SOD1, for SOD1-ALS.
Breathing and NIV Weak breathing muscles, the tests, and when ventilation is offered.
Swallowing and feeding tubes Why weight matters and when a gastrostomy is discussed.
Living with ALS Communication, cognition, symptoms, planning and end of life.
Nursing care Assessment, giving the medicines, teaching and documentation.
Toward a cure Every route under study, with the evidence for each.
History and people From Charcot to tofersen.
Flashcards, quiz and glossary Revision for students.
Sources Every reference behind the guide.

Part 3 · Treatment & care

Breathing and NIV

The breathing muscles weaken in ALS, slowly and often first at night. Scrub the timeline to watch the diaphragm, the FVC curve and one night's oxygen and CO2 change, and switch non-invasive ventilation (NIV) on or off. Then try the trigger checker to see how six guidelines read the same test results.

Timeline

Schematic, not to scale, and not one person's course. The FVC slope follows the Bourke cohort as summarised by AAN 2009 (about 2.2% a month before NIV, 1.1% after); SNIP, peak cough flow and the night traces are illustrative shapes. Threshold lines: FVC 80% (EFNS; NICE, Canada and the US panel with symptoms), 65% upright (Canada), 50% (AAN, NICE, US panel); SpO2 90% (US panel); CO2 45 mmHg (EFNS morning, Canada daytime). ^{70,145,332,401,470,543}

NIV trigger checker: six guidelines side by side

Enter test results and symptoms. The checker shows which published triggers each document lists are met by those values. It is an educational reading of the guidelines, not a recommendation: the documents frame these as triggers for discussion and referral, not automatic treatment, and it cannot say whether NIV is right for any one person. ^{145,332,401,470,506,543}

Load an example

Breathing tests FVC or VC, % predictedLeave blank if not measured

SNIP (sniff nasal inspiratory pressure), cmH2O MIP (maximal inspiratory pressure), cmH2OEnter the size: 55 for a reading of −55 SNIP or MIP fell by more than 10 cmH2O over 3 months

Symptoms and signs OrthopnoeaBreathless lying flat Other respiratory or night-time symptomsBreathlessness, disturbed or unrefreshing sleep, morning headaches, daytime sleepiness, poor concentration SignsFast or shallow breathing, weak cough or sniff, abdominal paradox, use of accessory muscles

Overnight oximetry and CO2 Overnight oximetry CO2 valueLeave blank if not measured

How each document words its triggers: AAN 2009 Figure 2; EFNS 2012 as tabulated by Dorst and Ludolph 2019 (the EFNS full text was not accessible, so these values are second-hand); NICE NG42 Table 2 and its blood-gas advice; the Canadian 2020 recommendations; the 2021 US technical expert panel (ONMAP), whose proposals are reimbursement criteria for neuromuscular disease in general; and EAN 2024, which gives no numbers. 6 kPa is about 45 mmHg. ^{20,145,332,401,470,506,543}

Living with NIV, cough, and the later choices

Adherence

NIV works when it is used for hours

Offered BiPAP below FVC 50%, people using it more than 4 h a day had a median survival of 14.2 months from the start, against 7.0 months with less use and 4.6 months when it was declined. ²⁶⁷
In one Italian centre, 44 of 71 people (61.9%) tolerated NIV for 4 h a day or more; mild or moderate bulbar symptoms predicted tolerance (OR 6.09). ²⁹⁹
Non-compliance was 75% in people with ALS and frontotemporal dysfunction against 38% in classic ALS; 94% of NIV users said they would choose it again. ³³²
Nasal masks are better tolerated and easier to talk through but can leak through the mouth with bulbar weakness; any mask can cause facial pressure sores. ¹⁴⁵

Early evidence: observational cohorts

Cough

Peak cough flow: 270 and 160 L/min

AAN 2009: peak cough flow above 160 L/min is needed to clear secretions, and clinicians recommend assistive devices below 270 L/min (Class III). The same 270 L/min mark triggered mechanically assisted coughing in Bach's single-centre series of 101 people. ^33,332
Mechanical insufflation-exsufflation raised peak cough flow by 26% in bulbar and 28% in non-bulbar patients, against 11-13% for manually assisted cough (Level C for clearing secretions). ³³²
NICE: breath stacking and/or manually assisted cough first, assisted breath stacking next, then a mechanical cough assist device; Canada suggests MI-E twice daily below 270 L/min (expert consensus). ^401,470
In a 40-person pilot RCT, breath stacking and MI-E did not differ significantly in chest infections, admissions or survival. Secretion problems are reported by 40-60% of people with ALS. ^60,442

Early evidence: small trials, consensus

Harm in trials

Diaphragm pacing shortened survival

The NeuRx pacing system received a US Humanitarian Device Exemption before any randomised data existed. ^143,145
DiPALS (UK, 74 people): median survival 11.0 months with NIV plus pacing against 22.5 months with NIV alone (adjusted HR 2.27); recruitment was stopped. ¹⁴³
RespiStimALS (France, 74 people, FVC 60-80%): NIV-free survival 6.0 months with active stimulation against 8.8 months with sham (HR 1.96); stopped for excess mortality. ²¹⁰
EAN 2024 makes a strong recommendation against diaphragm pacing in ALS. ⁵⁰⁶

Established: two RCTs found harm

Tracheostomy

Use differs widely by country

84% of US neurologists said fewer than 10% of their ALS patients had tracheostomy ventilation, against 32% of Japanese neurologists; over 70% in both groups would decline it for themselves. ⁴³⁹
9.5% in a German register (mostly without NIV first); 31.3% (87 of 279) in one Italian centre in 2001-2010; a US review states up to 95% in the US choose not to have it. ^403,479,481
In a propensity-matched Japanese registry, median overall survival was 11.33 years with it against 4.61 without. ²²³
In a German home-ventilation study, 81% of tracheostomy users had been tracheotomised without informed consent. EAN 2024 asks for it to be discussed in advance care planning so that emergency invasive ventilation can be avoided. ^256,506

End of life

Stopping ventilation at the person's request

The APM guidance (2015) states that in UK law a person with capacity may refuse or ask to withdraw assisted ventilation, invasive or not, and that withdrawal at their request is not assisted suicide. ²⁵
It states that the cause of death remains the disease, giving the wording "1a ventilatory failure (due to) 1b advanced motor neurone disease". ²⁵
In 95 UK accounts (2015-2024), 94% involved NIV and 92% of people were ventilator-dependent for more than 22 h a day; median time from removal to death was 30 minutes (10 minutes to over 54 hours), and 94% had medication beforehand, usually an opioid plus midazolam, titrated. ⁶⁴
NICE asks for support from professionals experienced in stopping NIV, the medicines and the legal frameworks. ⁴⁰¹

Tests

What the numbers predict

SNIP tracked diaphragm pressure (r = 0.9) and was the test most often still possible at the last visit (96%, against 86% for FVC and 81% for MIP). ³⁴⁸
For death within 6 months, FVC below 50% had 58% sensitivity and 96% specificity; SNIP below 40 cmH2O had 97% and 79%. ³⁴⁸
A mean night-time saturation below 93% went with a mean survival of 7 months against 18 months above it (Class IV). ³³²
With marked bulbar weakness no test predicted high CO2 (AAN 2009). NICE still measures SpO2 but not FVC, SNIP or MIP when severe bulbar or cognitive problems make the interfaces unsuitable, and since 2022 notes that oximeters may overestimate saturation in people with dark skin. ^332,401

Where the sources disagree

When to start. AAN 2009 uses FVC below 50%, while EFNS, NICE and Canada also count FVC below 80% with symptoms. Dorst and Ludolph argue that the EFNS criteria rest on opinion and that earlier NIV may be better; a sham-controlled pilot of early NIV (54 people) found a small FVC benefit and no survival difference, and how well people without symptoms keep using it is uncertain. ^{145,246,332,401}

Severe bulbar weakness. Bourke 2006 found no survival benefit in this subgroup, and NICE limits NIV there to possible benefit for sleep-related symptoms. EAN 2024 asks that every effort be made to allow NIV regardless of bulbar function, citing later retrospective data. ^{70,145,401,506}

Tracheostomy. Rates differ several-fold between countries and centres, and Rabkin's surveys suggest neurologists' attitudes, not only patients' preferences, account for part of the gap. ^{223,439,479,481}

For swallowing, weight and the feeding tube, which is timed against the same FVC curve, see Swallowing and feeding tubes.