Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. It causes loss of muscle control and paralysis due to the death of motor neurons. ALS is considered a rapidly progressive disease, with muscle weakness and atrophy developing over a course of just a few years. However, in some cases ALS follows a more gradual course, leading to questions about whether it can truly be slow progressing.
What is ALS?
ALS specifically affects motor neurons, which are nerve cells in the brain and spinal cord that provide the controlling signals for muscle movement. As motor neurons die, the brain loses its ability to initiate and control muscle movement. Without this controlling signal, muscles weaken and atrophy. ALS does not usually impair a person’s mind, personality or intelligence.
Eventually ALS affects control of the muscles needed to move, speak, eat and breathe. As muscle function deteriorates, people progressively lose the ability to walk, use their hands and arms, talk and swallow. Most people with ALS die from respiratory failure, usually within 3 to 5 years from the onset of symptoms.
However, about 10 percent of people with ALS survive for 10 years or longer. This raises the question of whether ALS can sometimes be a more slowly progressing disease.
Typical ALS Progression
ALS normally progresses quite rapidly after symptoms begin. The rate of progression can be measured using the ALS Functional Rating Scale (ALSFRS-R). This scale measures physical function in four domains:
– Fine motor tasks
– Gross motor tasks
– Bulbar symptoms (speech and swallowing)
– Breathing
Patients are scored from 0 to 4 in each domain, for total score of 0 to 48. A score of 0 indicates no usable function while a score of 48 indicates normal function in all areas.
In typical ALS, patients lose an average of about 1 point per month on the ALSFRS-R. This indicates a relatively rapid decline in physical abilities over time.
Some key facts about the usual rapid progression of ALS:
– Average survival time from onset to death is 3 to 5 years.
– About 50% of patients survive for ~3 years after symptoms begin.
– About 10% of patients survive for 10 or more years.
– Only 4% survive longer than 20 years.
– Decline is quite rapid once symptoms appear, averaging a 1 point per month decrease in ALSFRS-R score.
So while about 10% of ALS patients experience slower progression with longer survival, the overall course is still considered rapid and aggressive without treatment.
What is Considered Slow Progression in ALS?
There is no definitive cut-off for what is considered slowly progressive ALS. However, some key features that may indicate slower progression include:
– Survival longer than 10 years. While typical survival is 3-5 years, slower progression would likely involve surviving longer than the average patient. 10 years is sometimes used as a cut-off.
– Slower rate of decline on ALSFRS-R scale. Typical decline is 1 point per month. Slower progression may show a decline closer to 0.5 points per month.
– Slower loss of physical abilities. Patients may retain greater muscle strength and physical function for longer than typical.
– Muscle atrophy and weakness developing slowly over many years. Rapid progression can lead to significant atrophy in months, while slower progression shows less muscle wasting over years.
– Gradual onset of symptoms over longer timespan. Slow progression cases can have initial symptoms develop subtly over several years.
– Younger age at onset. Earlier-onset ALS is linked to slower progression in some cases.
So while “slow” is not precisely defined, key features include longer survival, slower rate of measured decline, slower muscle loss, subtle onset, and earlier age of onset.
What Factors Influence Slower Progression in ALS?
Researchers continue working to understand why some ALS patients experience a more gradual, slowly progressing form of the disease. Some factors that may play a role include:
Age at Onset
Younger age of onset, before age 45, has been associated with slower progression in some studies. Earlier-onset ALS may follow a more gradual course.
Site of Symptom Onset
Initial symptoms in the limbs, rather than bulbar region, may predict slower progression. Bulbar onset involves initial difficulty speaking or swallowing and portends faster progression.
Lack of Bulbar Involvement
Bulbar symptoms involving muscles for speaking and swallowing are linked with faster progression. Their absence may allow slower progression.
Type of Motor Neuron Affected
Loss of upper motor neurons (in brain) predicts faster progression compared to early loss of lower motor neurons (in spinal cord, brainstem).
Presence of Disease Modifiers
Gene modifiers or other factors may hinder the disease process. For example, C9orf72 gene abnormality predicts faster decline.
Environmental Factors
Unknown environmental variables could affect the disease course. For example, exercise and activity could theoretically slow progression.
The factors underlying slow progression are still under investigation. Identifyingmodifiers that hinder the disease could reveal therapeutic targets.
Characteristics of Slowly Progressing ALS Cases
Small proportions of ALS patients follow a more gradual, slowly advancing course. Some characteristics of these slow progression cases include:
Younger Age of Onset
Slowly progressing ALS patients tend to develop symptoms at a younger age, often before age 45. Earlier-onset disease may differ biologically.
Longer Time to Diagnosis
Slow progression can delay the definitive ALS diagnosis, with symptoms evolving subtly over years. Typical rapid ALS is diagnosed within about 12 months of symptom onset.
Lower Disability at Diagnosis
Slowly advancing patients have less significant disability and higher ALSFRS-R scores at diagnosis compared to typical rapidly progressing patients.
Limb Onset of Symptoms
Most patients with slow progression have initial symptoms in the limbs, like weakness of hands, arms, legs or feet. Bulbar onset involving speech/swallowing muscles predicts faster progression.
Longer Survival
Slow progressors survive significantly longer, with cases of 20+ years not uncommon. Average survival for typical ALS is only 3-5 years.
Younger Age at Death
Despite slower progression and longer disease duration, patients with slowly progressing ALS still die at a younger age than the normal population. However, they live decades longer than patients with typical rapidly advancing ALS.
Low Incidence of Dementia
Slowly progressing forms of ALS have a much lower likelihood of frontotemporal dementia compared to typical ALS. Dementia correlates with faster motor decline.
So while not fully understood, slowly progressing ALS does occur. Younger onset age, limb symptoms, lack of bulbar involvement, and lack of dementia help characterize more gradual cases.
Prognosis for Slow Progressing ALS
The long-term prognosis with slowly progressing ALS is better compared to typical rapidly advancing disease. However, patients still face eventual progression of weakness and associated disability. Key prognostic factors include:
Average survival around 15 years
Median survival is about 15 years for patients with slowly progressing ALS. This compares to just 2-4 years for most ALS patients.
High likelihood of being wheelchair bound
Nearly all slow progressors eventually require wheelchair use as leg muscles weaken. At 10 years, over 75% of patients are wheelchair dependent.
Most patients die from respiratory failure
Despite slower decline, most slowly progressing ALS patients eventually die due to respiratory muscle involvement leading to failure.
High risk of aspiration pneumonia
Weakness of bulbar muscles causes swallowing difficulty and aspiration risk. Aspiration pneumonia is a leading cause of death for slower progressors.
Potential for cardiac and pulmonary involvement
Slow progressors may also develop cardiac arrhythmias or respiratory muscle weakness that can worsen prognosis.
So while slowly progressing ALS patients live longer, nearly all will eventually develop significant weakness, swallowing issues, and respiratory impairment. However, the slower decline offers a much better long-term prognosis compared to typical ALS.
Key Takeaways
ALS is a rapidly progressive and fatal neurodegenerative disease in most cases. However, a small proportion of patients experience a more gradual, slowly progressing form of ALS. Key takeaways about this slowly progressing variant include:
– No firm criteria define slow progression, but features include longer survival, slower disability progression, subtle onset, and younger age at diagnosis.
– Factors like younger age of onset, site of initial symptoms, and lack of dementia may play a role in slow progression.
– Slow progressors live 10-20 years or longer, while typical survival is only 2-5 years.
– Slowly progressing patients still face high risks of weakness, swallowing impairment, and eventual respiratory failure.
– Understanding factors that slow ALS progression may reveal therapeutic targets to expand treatment options.
– Slowly progressing ALS represents an important subset providing insight into disease modifiers and variability.
So while most ALS patients undergo rapid progression, an important minority experience a more gradual form of the disease. Recognizing slow progressing ALS can refine diagnosis and prognostic predictions for these patients. Ongoing research aims to expand treatment options by leveraging knowledge from these unique long-term survivors.
Frequently Asked Questions
Can you live 20 years with ALS?
It is extremely rare to live 20 years or longer with ALS. However, a small subset of patients with slowly progressing disease can survive 2 decades or more. These long-term survivors represent only around 4% of all ALS patients.
What is the longest someone has lived with ALS?
The longest reported survivor with ALS lived to be 80 years old after being diagnosed at age 37. He required ventilator support from ages 45-80 and was confined to a wheelchair, but survived over 40 years with slowly progressing disease. Most ALS patients live only 2-5 years after diagnosis.
Can ALS symptoms come and go?
ALS symptoms and muscle weakness are usually persistent and gradually progressive over time. Temporary remissions or symptom fluctuations are quite rare. If symptoms seem to resolve and return, it may warrant re-evaluation for ALS or consideration of a different neurological diagnosis.
What helps slow down ALS?
There are no proven treatments that significantly slow progression of ALS long-term. However, managing symptoms, maintaining nutrition, using assistive devices, and remaining as active as possible can help stabilize patients. Several medications like Radicava may modestly slow decline in certain patients.
Can ALS progress fast then slow down?
In most cases, ALS follows a steady course after initial symptoms appear. Progression may be rapid or more gradual depending on subtype, but the rate of decline typically remains consistent over time. Sudden changes in progression speed are uncommon.
Conclusion
While ALS normally follows a relatively rapid course leading to significant disability within 2-5 years, a small subset of patients experience a more slowly progressing form of the disease. These cases present clues about factors that may slow the ALS disease process and extend survival by many years or even decades. Continuing to characterize and study slowly progressing ALS can provide hope for future treatments aimed at altering the speed of progression. In the meantime, recognizing slower progression can refine prognostic expectations and help guide management for these unique long-term survivors living with ALS.
