What is ALS?
What is ALS?Amyotrophic lateral sclerosis (ALS) is a progressive, incurable neurodegenerative disease that leads to the irreversible degeneration of motor neurons. Motor neurons are the nerve cells in the spinal cord and brain that initiate and control muscle movement.
Only about 2 out of every 100,000 people will get the disease each year, and it typically affects those between ages 40 and 70. More than 90% of ALS cases are sporadic (no clear family history), and 5% to 10% of ALS cases are familial (inherited through a mutated gene).1 Typically, the disease will progress over 2 to 5 years after diagnosis. However, 20% of patients live for more than 5 years, and about 5% live for 20 years or more.2
The name describes the condition. Amyotrophic comes from the Greek. A means “no,” myo refers to “muscle,” and trophic means “nourishment.” Lateral refers to the areas in the spinal cord where portions of the nerve cells that signal and control the muscles are located. As this area degenerates, it leads to scarring or hardening, known as sclerosis.
How does ALS progress?
It varies. It does not progress linearly: There is no “ALS timeline.” As the disease advances, muscle weakness and atrophy spread, leading to difficulties with moving, speaking or forming words (dysarthria), breathing (dyspnea) and swallowing (dysphagia). Dysphagia makes it difficult to eat. At the same time, people with ALS burn calories at a faster rate than average. As a result, they lose weight rapidly and become malnourished.3
Because ALS disease progression varies by the individual, precise staging is tricky. That’s one reason the reason many clinicians — at least when dealing with patients and caregivers — will frame ALS progression in terms of three broad categories: early, middle and late. Some will add a fourth, termed the “end” or “final” stage.
Early-stage ALS
The first signs of ALS often occur long before diagnosis. It initially manifests one of two ways: as weakness in the limbs, called limb (or spinal) onset, or difficulty in speaking or swallowing, termed bulbar onset.4 Limb onset is far more common.5
Early symptoms can include muscle weakness, spasticity (tightness), cramping, and/or fasciculations (twitching). Because this frequently begins in the arms or hands, it makes daily tasks challenging. Symptoms typically start in one region of the body, although mild symptoms may affect other areas. The person may feel fatigued, have poor balance, have a weak grip or stumble when walking.
Bulbar-onset ALS begins in the face or neck. Early symptoms include slurred speech and hoarseness. The person may be experiencing ALS throat symptoms like difficulty chewing and swallowing — aspirating or choking while eating.6,7
Middle-stage ALS
How fast does ALS progress after the first symptoms? In the middle stage of ALS, the early-stage symptoms become worse. Muscle atrophy will spread to other parts of the body, increasing weakness. Some muscles become paralyzed, and some may become shortened, preventing joints from fully straightening.8
Overall weakness increases and walking becomes more challenging. If the person falls, they may not be able to get back up on their own. Driving is no longer an option, and the individual may need help with the activities of daily living.
Swallowing and chewing may become increasingly difficult over time, and the risk of choking increases. Breathing also becomes harder.
Some people experience uncontrollable bouts of laughing, called the pseudobulbar affect. These happen completely randomly and aren’t related to outside stimuli.
Late-stage ALS
In advanced ALS, most voluntary muscles are paralyzed, including those of the mouth and throat. So are those involved in breathing. Poor respiration can lead to fatigue, headaches and impaired thinking.9 It also increases their susceptibility to pneumonia. Ultimately, they may need to rely on a ventilator. Mobility is extremely limited. Talking and swallowing become more difficult. That makes eating exceptionally difficult, and the individual eventually will require a feeding tube.
Final stages of ALS
ALS is always fatal, and most deaths result from respiratory failure. Medications can relieve discomfort, anxiety and fear caused by respiratory insufficiency.
Hospice care helps ensure the person with ALS has the most peaceful, dignified and painless experience possible. In general, patients with a prognosis of six months or less are considered eligible for hospice, but that varies. Only a physician can make a prognosis, but these signs suggest that the person may be ready for hospice:10
Speech has become barely intelligible, unintelligible or impossible.
The person with ALS needs considerable assistance with — or is totally dependent on others for — eating, dressing and grooming.
The patient does not wish to be dependent on feeding tubes for nutrition and hydration
The patient does not want to be placed on a ventilator or wishes to discontinue mechanical ventilation
Hospice care can control pain and help manage symptoms while providing emotional and spiritual support for the person with ALS and their family. In addition, patients using hospice care are more likely to stay in their preferred location, die outside the hospital and receive appropriate pain management.11
How long does the final stage of ALS last? Patients who are in the terminal stage of the illness have a life expectancy of six months or less.
Turning to more precise staging
Framing ALS disease progression based on these four simple stages makes sense for helping patients and families understand what lies ahead. But for researchers and many physicians, it’s inadequate. Staging ALS is imprecise. The very nature of the disease means that there will never be a perfect way to measure progression, but researchers need more exact staging tools.
One, the Milano-Torino staging system (MiToS), is based on functional ability. It focuses on a number of functional domains with a loss of independent function: movement (which includes walking and self-care), swallowing, communicating and breathing.12
Another, more common, approach is the King’s ALS clinical staging system. It assesses anatomical spread of ALS based on the number of affected regions (bulbar, upper limb and lower limb). It also includes advanced stages defined by nutritional or respiratory failure.13 Scores range from Stage 1 for early disease with one region involved, to Stage 4, for late disease:
Stage 1: Symptom onset (involvement of first region)
Stage 2A: Diagnosis (35% of the way through the disease course)
Stage 2B: Involvement of second region (38%)
Stage 3: Involvement of third region (61%)
Stage 4A: Need for gastrostomy (a feeding tube) (77%)
Stage 4B: Need for noninvasive ventilation (80%)
A 2020 study found that both systems may effectively assess changes in patients’ clinical progression and treatment responses.14
Why accurate staging matters
Accurate staging is not only essential for clinical trials, but it may also inform how clinicians discuss ALS with patients and caregivers. “The independent and complementary nature of the 2 systems, one tracking anatomical spread of disease (the King’s Clinical Staging System) and the other focusing on loss of function (the MiToS system), means they can provide different insights that may be particularly important in counselling patients on the potential benefits of therapy,” the researchers wrote.14 [1]
Much remains unknown about this disease, and researchers around the world are trying to learn more develop new ALS therapies and diagnostics. To learn about some of these efforts, visit www.targetals.org/research/.
Notes
- Genetic Testing for ALS. ALS Association https://www.als.org/understanding-als/who-gets-als/genetic-testing
- Amyotrophic Lateral Sclerosis (ALS) Fact Sheet National Institute of Neurological Disorders and Stroke
- National Institute of Neurological Disorders and Stroke op. cit.
- https://alsnewstoday.com/forms-of-als/
- https://www.als.net/news/science-sunday-limb-and-bulbar-onset-als/
- https://emedicine.medscape.com/article/1170097-overview
- https://alsnewstoday.com/stages-of-als/
- https://alstreatment.com/als-progression-timeline/
- https://www.vitas.com/care-services/personalized-care-plans-by-diagnosis/als-lou-gehrigs-disease
- https://www.compassus.com/for-caregivers/is-it-the-right-time-for-hospice/end-of-life-care-for-als
- https://alsnewstoday.com/news-posts/2020/12/02/two-als-staging-systems-may-be-useful-assessment-tools-in-clinical-trials-study-suggests/
- Roche JC, Rojas-Garcia R, Scott KM, et al. A proposed staging system for amyotrophic lateral sclerosis. Brain. 2012;135(Pt 3):847-852. doi:10.1093/brain/awr351
- Ibid.
[1] Ibid.
