What's amyotrophic lateral sclerosis?
Amyotrophic lateral sclerosis is a progressive neurodegenerative disease of the upper and lower motor neurons, producing combined signs of muscle weakness and wasting with fasciculations (lower motor neuron) and spasticity with brisk reflexes (upper motor neuron). Onset may be limb or bulbar (dysarthria, dysphagia); respiratory failure is the usual cause of death, while sensation and, for most patients, cognition are relatively spared, with a frontotemporal dementia overlap in a minority. About 90% of cases are sporadic and roughly 10% familial, with C9orf72 and SOD1 the most common familial causes (TARDBP and FUS next); ALS is not generally inherited. There is no cure. Riluzole and edaravone offer modest benefit, tofersen is an antisense therapy specific to SOD1-related ALS, and multidisciplinary care including respiratory support (such as noninvasive ventilation), nutrition, and symptom management is central to extending survival and protecting quality of life.
| Also indexed as | ORPHA:803, MONDO:0004976 |
|---|---|
| Features mapped | 19 |
| Treatments mapped | 6 |
| Published sources | 14 |
| Last reviewed | 2026-08-04 |
Signs and symptoms
Upper limb muscle weakness
Amyotrophic lateral sclerosis often starts with painless weakness in one part of the body. When it begins in a limb, it can show up as weakness in the hand. The weakness then spreads to other regions over time.
Frontotemporal dementia
While thinking is preserved in most people, some develop frontotemporal dementia, which affects behaviour and language. ALS and this form of dementia share underlying biology, including TDP-43 changes and C9orf72.
Neurodegeneration
Neurodegeneration was thought to be mainly caused by proteins clumping together, but scientists now know that RNA also actively drives the disease.
Fasciculations
Fasciculations are fine, involuntary muscle twitches visible under the skin. They reflect lower-motor-neuron irritation and are a common early sign.
Hyperreflexia
Overactive (brisk) reflexes are a sign of upper-motor-neuron involvement and, alongside the muscle wasting of lower-motor-neuron loss, point to the combined picture typical of ALS.
Paralysis
As amyotrophic lateral sclerosis progresses, the loss of motor neurons can lead to paralysis, meaning a loss of the ability to move affected muscles.
Dysarthria
Slurred or difficult speech (dysarthria) is common when the muscles of the mouth and throat are affected, and for some people it is the first symptom.
Dysphagia
Difficulty swallowing (dysphagia) develops as the tongue and throat muscles weaken. It affects nutrition and raises the risk of food or fluid entering the lungs, so it is managed actively.
Dyspnea
Dyspnea is the feeling of struggling to breathe, and it can be a major physical and emotional burden. In ALS it comes from weakening of the muscles used for breathing, not from a disease of the lungs themselves.
Respiratory failure
As the muscles that control breathing weaken, breathing becomes harder over time. Breathing support, such as noninvasive ventilation, becomes an important part of care and is the main reason the disease shortens life.
Spasticity
Spasticity, stiffness and tightness of the muscles, comes from upper-motor-neuron involvement and can affect movement and comfort.
Generalized muscle weakness
ALS is a disease in which nerve cells that control muscles gradually break down, causing muscles to weaken and shrink.
Skeletal muscle atrophy
As the motor neurons that drive movement are lost in amyotrophic lateral sclerosis, the muscles they supply can waste away. This wasting is called muscle atrophy.
Adult onset
ALS starts in adulthood and gradually destroys the nerve cells in the brain and spinal cord that control movement.
Degeneration of the lateral corticospinal tracts
In amyotrophic lateral sclerosis, the upper motor neurons in the brain break down over time. This degeneration is part of what produces the progressive weakness of the condition.
Degeneration of anterior horn cells
In amyotrophic lateral sclerosis, the lower motor neurons in the brainstem and spinal cord break down over time. This degeneration is part of what produces the progressive weakness of the condition.
Autosomal dominant inheritance
When ALS is linked to an identified causal gene variant, it is most often inherited in an autosomal dominant manner, meaning a single altered copy of the gene is enough to cause it.
Pseudobulbar paralysis
Amyotrophic lateral sclerosis usually shows signs of both upper motor neuron problems (muscle stiffness and spasticity) and lower motor neuron problems (weakness, muscle twitches, wasting, and floppiness) at the same time.
Muscle weakness
Progressive muscle weakness with wasting (atrophy) is the central feature, as the motor neurons that drive the muscles are lost. It often starts in one limb or in speech and swallowing and spreads over time.
How it is diagnosed
Amyotrophic lateral sclerosis
Diagnosed using: Next-generation sequencing.
“DNA samples from 244 index patients were screened for variants in the pathogenic genes SOD1, FUS, TDP43, and C9ORF72, of which 146 were also subjected to genome-wide next-generation sequencing.”
Amyotrophic lateral sclerosis
Diagnosed using: electromyography.
“Amyotrophic lateral sclerosis is diagnosed based on clinical features, which can be supported by results of electromyography.”
Amyotrophic lateral sclerosis
Diagnosed using: revised El Escorial criteria.
“Phenotypic heterogeneity, manifesting as bulbar-, spinal-, or respiratory-onset variants, complicates its early diagnosis, which thus necessitates the rigorous application of the revised El Escorial criteria and emerging biomarkers such as neurofilament light chain.”
Treatment and management
What the research describes, not a recommendation. Treatment decisions belong with your clinician.
This covers treatments that appear in the published research mapped here. Investigational and experimental therapies are not included, so their absence is a boundary of this map, not a sign they do not exist.
riluzole
Riluzole is the longest-established medicine for ALS. It modestly extends survival, and although the effect is limited it is a standard part of treatment.
Used to help with: Amyotrophic lateral sclerosis.
“Compared to placebo, ALS patients taking riluzole had 36% higher probability of surviving (OR: 1.36, I2 = 4%, p = 0.03, FEML) while those in the edaravone group had 1.44 point lower ALSFRS-R score (SMD: 1.44, p = 0.19, I2 = 98%, REML) at study end.”
noninvasive ventilation
Noninvasive ventilation is breathing support delivered through a mask rather than a tube. Used early as the breathing muscles weaken, it improves quality of life and survival and is a central part of supportive care.
Used to help with: Amyotrophic lateral sclerosis.
“This article explores the role of early noninvasive ventilation in improving the quality of life and survival rates in patients with amyotrophic lateral sclerosis (ALS).”
tofersen
Tofersen targets a specific genetic form of ALS linked to changes in the SOD1 gene. Like riluzole and edaravone, it can ease the disease but cannot prevent or halt it.
Used to help with: Amyotrophic lateral sclerosis.
“Drugs like riluzole, edaravone, and tofersen treat disease symptoms or are designed for a specific pathological mutation (e.g., SOD1), but they cannot prevent or halt the disease.”
dextromethorphan/quinidine
Dextromethorphan/quinidine has been reported to reduce bulbar symptoms in amyotrophic lateral sclerosis, including difficulty speaking (dysarthria) and difficulty swallowing (dysphagia).
Used to help with: Amyotrophic lateral sclerosis.
“In amyotrophic lateral sclerosis (ALS), dextromethorphan/quinidine (DMQ) has been reported to reduce bulbar symptoms, including dysarthria and dysphagia.”
multidisciplinary care
Care from a specialized multidisciplinary team of neurologists, nurses, therapists, dietitians, and social workers is associated with improved survival and quality of life in amyotrophic lateral sclerosis.
Used to help with: Amyotrophic lateral sclerosis.
“Specialized multidisciplinary teams, comprising neurologists, nurses, therapists, dietitians, and social workers, are associated with improved survival (4-7 months) and quality of life.”
edaravone
Edaravone is an oral medication that is associated with slowing the progression of amyotrophic lateral sclerosis by up to 2 to 4 months.
Used to help with: Amyotrophic lateral sclerosis.
“Riluzole and edaravone are oral medications that slow ALS progression by up to 2 to 4 months, and tofersen is an intrathecally administered gene therapy for patients with SOD1 gene variants.”
How to read the evidence labels
Where this comes from
This guide is built from 14 published source(s). Every claim above links back to one of them. Click any source ID to read the original on PubMed.
Take it further
Printed, source-linked documents built from this condition's graph — ready to bring to an appointment or attach to a coverage request. Every claim carries its published source, the same as this guide.