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 2 · Diagnosis & course

The differential: ALS mimics

Several conditions can look like ALS early on, and some of them are treatable. Press Play to walk the decision points doctors describe, then pick a condition to see where it branches off and which test separates it.

Pick a condition

Decision points

A teaching simplification of published reviews. Real work-ups run several of these checks at once and repeat them over time.

Conditions and features

Each row is a condition from the reviews read for this guide; the first row is ALS itself for reference. A dash means the feature is not described for that condition in those sources. Click a row, or use the buttons above, to show where the condition branches off in the tree.

Condition	UMN signs	LMN signs	Sensory	Sphincters	Eye movements	Pace	Key test

Also named in the same reviews: neuralgic amyotrophy (severe pain at onset, then arrest), Hirayama disease (young men, one-sided C7–T1 weakness, flexion MRI), adrenomyeloneuropathy (very-long-chain fatty acids), primary progressive MS (MRI, CSF bands), paraneoplastic syndromes and adult polyglucosan body disease. ^194,202,502

Red flags for another diagnosis

Prominent sensory featuresCopper deficiency, CIDP, Kennedy disease
Sphincter, visual or autonomic disturbanceMyelopathy, HSP
Basal ganglia signsParkinsonian syndromes, hexosaminidase A deficiency
Abnormal eye movementsMyasthenia gravis
Fluctuating or fatigable weaknessMyasthenia gravis
Severe pain at onsetNeuralgic amyotrophy; brachial radiation plexopathy
Conduction block or demyelinationMMN, CIDP
Weakness out of proportion to wastingMMN
No progression over timeBenign fasciculations, other slow mimics

Red flags as listed across the sources; the conditions under each are examples drawn from the table above. ^{133,194,202,413,502}

How often the first diagnosis changes

7.3%

Irish ALS Register

Of 437 referrals in 1993–1997, 32 were later rediagnosed. Multifocal motor neuropathy (7, 22%) and Kennedy disease (4, 13%) were the commonest. 84% of the mimics had met only the "suspected" or "possible" El Escorial levels, 13% "probable" and 3% "definite". ⁴⁹⁷

Scottish MND Register

Of 552 people registered, 46 had another diagnosis, and a potentially beneficial treatment existed for half of them. Failure to progress, atypical features or test results prompted the revision. ¹³³

≈10%

Across population studies

Nearly 10% of people diagnosed with ALS turn out to have another condition, and a few conditions account for most of these. No register figure more recent than these two was found for this guide. ^202,502

Exam hookTreatable mimics to exclude: MMN (conduction block, anti-GM1, IVIG), cervical spondylotic myelopathy (neck pain, sphincters, nothing above the neck; MRI), bulbar myasthenia (fatigable, ptosis; RNS and antibodies) and Kennedy disease (low SNAPs, gynaecomastia, CAG expansion in AR). ^{194,284,285,502}

In plain wordsSeveral other conditions can look like ALS early on, some of them treatable, so doctors check for them first. Numbness, double vision, bladder trouble or weakness that comes and goes are clues that something else may be going on.