Amyotrophic lateral sclerosis (ALS), known in France as Charcot’s disease, gradually destroys the nerve cells that control voluntary muscles, and the early signs of ALS are often subtle. It usually begins between the ages of 50 and 70 with a single discreet change: a less nimble hand, a foot that catches, speech that turns thick and slurred. In Europe, it affects about 2 people per 100,000 each year. Recognizing these first signs early shortens a diagnostic odyssey of nearly a year and opens access to specialist care.
In brief – ALS, called Charcot’s disease in France, is a rare neurodegenerative disease that destroys motor neurons in both the brain and the spinal cord. The result is muscle weakness that spreads step by step from one region to the next. The early signs of ALS affect a limb in about two thirds of cases: a clumsy hand, a foot that catches, a wasting muscle. In one third of cases, they involve speech or swallowing, with slurred speech or choking on liquids. Three features should raise concern: real weakness, progressing from one month to the next, with no tingling or loss of sensation. By contrast, isolated twitches with normal strength are almost always benign. In a Mayo Clinic cohort, none of the 121 patients followed for up to 32 years developed motor neuron disease. When a sign looks suspicious, your primary care doctor refers you to a neurologist, and electromyography remains the key test.
What is ALS?
ALS stands for amyotrophic lateral sclerosis, a degeneration of the motor neurons described by the neurologist Jean-Martin Charcot at the Salpêtrière hospital in Paris in the 19th century. In the United States it is also called Lou Gehrig’s disease, after an American baseball player diagnosed in 1939, while France still calls it Charcot’s disease. It spares sensation and, in general, eye movements: the person feels normally, but their muscles obey less and less well.
The name describes the lesion. “Lateral sclerosis” refers to the hardening of the lateral columns of the spinal cord, where the fibers of the upper motor neuron run. “Amyotrophic” means that the muscle wastes away for lack of nerve input. The first signs usually appear between the ages of 50 and 70. According to MedlinePlus, the health information service of the US National Library of Medicine, death typically occurs 3 to 5 years after symptoms begin, with wide individual variation.
ALS remains rare. A systematic review of 37 studies puts the European incidence at 2.08 new cases per 100,000 inhabitants per year. Prevalence there reaches 5.4 cases per 100,000 (Chiò et al., 2013). A worldwide meta-analysis of 44 studies, covering 13,146 patients, found a standardized rate of 1.68 per 100,000 person-years. This rate is higher in Northern Europe than in East Asia (Marin et al., 2017).
Watch out for similar names. Charcot-Marie-Tooth disease, an inherited neuropathy that affects the peripheral nerves and sensation, has nothing to do with ALS. “Charcot foot”, for its part, is a bone complication of diabetes.
Why ALS weakens the muscles
ALS strikes two successive nerve relays. The upper motor neuron sits in the motor cortex, the lower motor neuron in the spinal cord and brainstem. When the lower one disappears, the muscle is no longer stimulated: it wastes away and starts to twitch. When the upper one fails, movements become stiff and slow.
This double damage is the signature of ALS and explains the unusual mix of signs a neurologist looks for. Its causes remain partly unknown, but four mechanisms are now documented.
- Protein aggregation: in 2006, a Philadelphia team identified the protein TDP-43 as the main component of the abnormal inclusions found in diseased motor neurons (Neumann et al., 2006). This failure of protein recycling links ALS to the loss of proteostasis, one of the hallmarks of cellular aging.
- Genes: about 10% of cases are familial, according to Inserm, France’s national institute for health and medical research. A repeat expansion in the C9orf72 gene is present in one third of familial cases of European ancestry. It is the most common genetic cause identified to date (Renton et al., 2011).
- Excess glutamate: in excessive amounts, this neurotransmitter overstimulates and then exhausts motor neurons. Riluzole, the first approved drug, targets this pathway.
- Energy and inflammation: Inserm describes failing mitochondria and chronic activation of the brain’s immune cells, the microglia, which fuel progression.
In early ALS, the muscles compensate for the loss of neurons. The remaining nerve fibers take over the muscle fibers left behind, a process called reinnervation. Weakness only becomes visible once this compensation is overwhelmed, which explains why the disease often starts so quietly.
| Neuron affected | Location | What the person notices | What the neurologist looks for |
|---|---|---|---|
| Upper motor neuron | Motor cortex of the brain | Stiffness, slow and clumsy movements, uncontrollable laughing or crying | Brisk reflexes, Babinski sign, spasticity |
| Lower motor neuron | Spinal cord and brainstem | Weakness, muscle wasting, fasciculations, cramps | Muscle atrophy, visible fasciculations, abnormal electromyography findings |
The 8 early signs of ALS according to science
The early signs of ALS are focal: they start in a single region of the body, often on one side, then spread to neighboring regions. In a cohort of 304 patients followed in Boston, three initial signs sped up the diagnosis: fasciculations, slurred speech and leg weakness (Paganoni et al., 2014).
1. A hand that loses its dexterity
This is the most classic onset of ALS in its spinal form. Buttoning a shirt, turning a key or picking up a coin becomes laborious, with no pain or numbness. The muscle between the thumb and index finger often wastes before the one at the base of the little finger. This “split hand” sign is rarely seen in other diseases and proves highly specific (Eisen and Kuwabara, 2012).
2. A foot that catches, or unexplained falls
Weakness in the muscles that lift the foot makes you trip on a rug or a step, sometimes on one side only. The foot then slaps the ground with each stride. In ALS, this sign is often blamed at first on sciatica or a worn hip. In the Boston study, 52% of patients had received another diagnosis before ALS, after seeing an average of three doctors.
3. Localized muscle wasting
A hollow appears on the back of the hand, at the shoulder or in the calf, while overall body weight stays stable. This asymmetric wasting sets ALS apart from age-related muscle loss, which remains diffuse and symmetrical. The affected muscle loses strength at the same time as volume.
4. Twitching and cramps alongside weakness
Fasciculations are small involuntary contractions visible under the skin. In ALS, they come with weakness or wasting of the same muscle, and with unusual cramps, sometimes in the thigh, the hand or the abdomen. Isolated twitches with normal strength do not carry this meaning.
5. Slurred or nasal speech
The bulbar form accounts for about one third of cases, according to Inserm. Speech becomes slow and poorly articulated, or the voice sounds nasal. Family and friends often notice it before the person does. A Cleveland Clinic review of 21 studies shows that bulbar onset shortens the time to diagnosis (Richards et al., 2020).
6. Choking on liquids and drooling
Drinking triggers coughing, meals take longer, and saliva builds up because it is swallowed less well, not because too much is produced. The tongue may thin and quiver at rest. These problems raise the risk of malnutrition and aspiration pneumonia, which is why they are worth raising with a doctor early.
7. Unexplained weight loss
Weight drops without dieting, driven by muscle wasting, eating difficulties and higher energy expenditure. A team in Limoges, France, followed 92 patients: each 5% loss of usual body weight at diagnosis raised the risk of death by 30% (Marin et al., 2011). Nutrition is therefore part of treatment from the very start.
8. A change in behavior, or uncontrollable laughing and crying
Apathy, disinhibition, and trouble finding words or planning can precede or accompany the motor signs. According to the consensus criteria revised in 2017, neuropsychological deficits affect more than 50% of people with the disease (Strong et al., 2017). Bouts of disproportionate laughing or crying, known as pseudobulbar affect, reflect upper motor neuron damage and do not necessarily match the mood the person actually feels.
| Type of onset | Share of cases | Typical first signs | Distinctive feature |
|---|---|---|---|
| Spinal (arms, legs) | About two thirds | Clumsy hand, foot that catches, a wasting muscle, cramps | Later diagnosis, especially after 60 |
| Bulbar (speech, swallowing) | About one third | Slurred or nasal speech, choking on liquids, quivering tongue | Faster diagnosis, more guarded outlook |
| Respiratory | Very rare | Shortness of breath when lying down, morning headaches, daytime sleepiness | Most severe form, according to Inserm |
The delay between the first sign and the diagnosis remains long: a median of 11.5 months in Boston, and 10 to 16 months in the Cleveland Clinic review. It grows longer after 60, in sporadic forms, and when ALS begins in a limb. A European review confirms that older age and bulbar onset are associated with shorter survival (Chiò et al., 2009).
Harmless symptom or ALS warning sign: how to tell the difference
Most people who fear they have ALS do not have it. Isolated fasciculations are the textbook example. At the Mayo Clinic, 121 patients with benign fasciculations, a normal examination and a normal electromyogram were contacted again 2 to 32 years later. None had developed motor neuron disease (Blexrud et al., 1993).
A telling detail: 40 of these 121 patients worked in health care, a field that knows ALS well and where people watch their own muscles closely. Nineteen had noticed their twitching after a viral infection. Coffee, lack of sleep and intense exercise are other frequently reported triggers.
Three criteria call for a prompt medical visit. The first is objective weakness: a movement becomes impossible, not just tiring. The second is progression from one month to the next, the third the absence of sensory symptoms. ALS rarely causes tingling, burning or loss of sensation, which point instead to a pinched nerve or a neuropathy.
| What you notice | Rather reassuring | Reason to see a doctor |
|---|---|---|
| Twitching | Widespread, shifting, normal strength, stable for months | Localized in a muscle that is weakening or wasting |
| Cramps | Calves at night, after exertion or dehydration | Frequent, in unusual areas, with loss of strength |
| Clumsy hand | Tingling fingers at night, joint pain | Painless loss of strength, hollow between thumb and index finger |
| Foot that catches | Low back pain running down the leg with numbness | Painless foot drop that worsens month after month |
| Change in voice | Hoarseness during a cold, gone within 3 weeks | Persistent slurred speech, with episodes of choking |
| Muscle fatigue | General tiredness after a bad night or an infection | Localized weakness that prevents a specific movement |
A diffuse, symmetrical loss of strength after 60 is most often due to sarcopenia, covered in our article on muscle loss. Measuring your grip strength once a year gives an objective benchmark and helps spot an asymmetry between the two hands. A resting tremor and slowed movements point more toward Parkinson’s disease. Both diseases share a failure to clear damaged proteins, explained in our pillar page on the loss of proteostasis.
What to do about possible early signs of ALS
When weakness is progressing, the right step is a prompt medical visit rather than anxious searching online. Your primary care doctor checks strength, reflexes and sensation, then refers you to a neurologist if needed.
- Note the date of onset, the side affected and the movements that have become difficult: this log makes any progression objective.
- Weigh yourself every week and report any unintended weight loss.
- Ask someone close to you to film a short clip of you speaking or walking, to compare from one appointment to the next.
- Seek care without delay in case of repeated choking, shortness of breath when lying down, or falls.
- Ask whether electromyography (EMG) is indicated: this test records the electrical activity of nerves and muscles.
- If the diagnosis is being considered, ask for a referral to a specialist ALS center; France has about twenty, according to Inserm.
The diagnosis remains clinical and requires ruling out the diseases that mimic ALS: compression of the cervical spinal cord by arthritis of the neck, multifocal motor neuropathy, myasthenia gravis or certain myopathies. The Gold Coast criteria first require a progressive motor deficit and the exclusion of other causes. They also require signs of both motor neurons in one region, or of the lower motor neuron in two regions (Shefner et al., 2020). An MRI and blood tests complete the electromyography.
No treatment can stop ALS today, but several measures extend survival or preserve quality of life. Their effects, as measured in studies, are summarized below.
| Measure | Study | Main result |
|---|---|---|
| Riluzole 100 mg per day | Bensimon et al., 1994 (155 patients) and Miller et al., 2012 (1,477 patients) | Median survival raised from 11.8 to 14.8 months, a gain of 2 to 3 months |
| Non-invasive ventilation | Bourke et al., 2006 (41 randomized patients) | 205 more days of median survival when swallowing is preserved, quality of life maintained |
| Follow-up at a multidisciplinary clinic | Traynor et al., 2003 (344 Irish patients, observational study) | Median survival extended by 7.5 months, one-year mortality reduced by 29.7% |
| Tofersen (SOD1 mutation) | Miller et al., 2022 (108 patients) | Lower levels of SOD1 protein and neurofilaments, primary clinical endpoint not met at 28 weeks |
Tofersen shows why early detection matters. In the trial extension, patients treated from the start lost 3.5 fewer points at 52 weeks on the ALSFRS-R functional rating scale. The comparison is with patients who started 28 weeks later and remains exploratory. Inserm presents it as the first drug that appears to slow ALS, reserved for a minority of patients who carry a mutation in the SOD1 gene. To follow research advances on neurodegenerative diseases, sign up for our health newsletter.
Frequently asked questions about ALS
Can isolated twitches be early signs of ALS?
Very rarely. Fasciculations with normal strength and a normal neurological examination are almost always benign. In a Mayo Clinic cohort, none of the 121 patients followed for 2 to 32 years developed motor neuron disease. What should raise concern is twitching combined with weakness or wasting of the same muscle, progressing from one month to the next.
What is the difference between ALS and multiple sclerosis?
Multiple sclerosis is an autoimmune disease that attacks the myelin sheath of the nerves, mainly affects young adults and often progresses in relapses. It frequently causes problems with sensation or vision. ALS destroys the motor neurons themselves, tends to begin between 50 and 70, progresses without remission and spares sensation.
Which test confirms ALS?
No single test is enough. The neurologist relies on the clinical examination and on electromyography, which reveals motor neuron damage even in muscles that are still strong. An MRI of the brain and cervical spinal cord, along with blood tests, rules out the diseases that mimic it. The international Gold Coast criteria, proposed in 2020, formalize this reasoning.
Is ALS hereditary?
In about 10% of cases, according to Inserm, the disease runs in families and is linked to a mutation, most often in the C9orf72, SOD1, TARDBP or FUS genes. In nine cases out of ten, it occurs with no family history. Genetic testing should be discussed with a neurologist and a genetic counselor, because it can open access to a targeted treatment such as tofersen.
What is the life expectancy with ALS?
Median survival from the first signs ranges from 20 to 48 months depending on the study. Yet 10 to 20% of patients live more than 10 years, according to a European review published in 2009. Older age and bulbar onset worsen the outlook. Riluzole, non-invasive ventilation, nutritional support and care at a specialist center extend survival.
Can ALS be prevented?
No measure has been shown to prevent the disease. Smoking and certain occupational exposures are being studied as risk factors, with no causal link established. The only real room for action lies in detection. Recognizing progressive weakness early gives faster access to diagnosis, clinical trials and the care that prolongs survival.
Medical disclaimer. The information provided here is for informational purposes only and does not constitute medical advice. It does not replace a consultation. Ask a healthcare professional before changing your diet, taking dietary supplements or starting a new practice, especially if you have a medical condition, are pregnant or are under treatment. Dietary supplements do not replace a balanced diet or medical follow-up. Progressive muscle weakness, or trouble speaking or swallowing, warrants a prompt medical visit.
