ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. The key word being “progressive” – ALS causes worsening muscle weakness, disability and eventual paralysis over time. So can ALS truly come on slowly and gradually? Or does it always involve rapid progression of symptoms? Let’s take a closer look.
What is ALS?
ALS stands for Amyotrophic Lateral Sclerosis. It is a motor neuron disease that progressively damages and kills the nerve cells responsible for controlling voluntary muscle movement. Over time, as motor neurons degenerate and die, the brain loses its ability to initiate and control muscle movement.
The most common early symptoms of ALS include:
- Muscle weakness in the arms, legs, mouth or throat
- Twitching and cramping of muscles (fasciculations)
- Difficulty speaking and swallowing (dysarthria and dysphagia)
- Tripping or falling
As ALS advances, muscle weakness and atrophy spread throughout the body. This leads to complete paralysis and problems with breathing, eating, speaking and other basic functions. Although ALS does not directly affect the senses or a person’s cognitive abilities, most people with ALS die from respiratory failure within 2-5 years from the onset of noticeable symptoms.
At this time, there is no cure for ALS and treatment focuses on relieving symptoms and maintaining quality of life for as long as possible. Riluzole is the only FDA-approved medication for ALS and has been shown to prolong survival by just a few months. Ultimately, ALS causes devastating disability and remains a fatal disease.
Is there a slow progression form of ALS?
The clinical course of ALS is highly variable from one person to another. In most cases, ALS follows a classic pattern of progressive loss of motor function and relatively rapid decline over 2-5 years. However, ALS can also sometimes follow an atypical, slow course.
Primary lateral sclerosis (PLS)
In primary lateral sclerosis (PLS), the disease progresses much more gradually than typical ALS. Muscle weakness and spasticity slowly accumulate over many years, usually starting in the legs. In PLS, loss of upper motor neurons leads symptoms like stiffness, spasms, and walking difficulties. PLS differs from ALS in that people with PLS generally don’t develop lower motor neuron signs like muscle atrophy and twitching.
Many neurologists consider PLS to be a variant form of ALS that involves selective degeneration of upper motor neurons. Progression of PLS may span more than 10-15 years in some cases. Eventually most patients do develop some lower motor neuron features consistent with ALS.
Progressive muscular atrophy (PMA)
Progressive muscular atrophy (PMA) is another atypical slow variant of ALS. In PMA, there is progressive lower motor neuron loss leading to muscle atrophy and weakness. However, upper motor neuron signs like spasticity and hyperreflexia are generally absent, at least early on. Cases of PMA may progress slowly over more than a decade before any signs of upper motor neuron damage appear. Like PLS, many experts think PMA represents a subtype of ALS.
Factors that influence rate of progression in ALS
While slow forms of ALS like PLS and PMA do exist, they only account for about 10% of ALS cases. In typical ALS, the rate of progression can vary quite a bit from one person to the next. What factors play a role in determining how rapidly someone’s ALS will advance?
Age of onset
Younger people with ALS tend to experience a more aggressive form of the disease with faster progression of symptoms. Older age of onset (over 70 years old) is linked to slower progression on average.
Site of onset
The initial site of symptom onset often correlates with progression rate. ALS that begins in the arms or legs is associated with slower progression compared to ALS that starts with bulbar symptoms like speech or swallowing difficulties. Bulbar onset ALS carries the worst prognosis.
El Escorial criteria
The El Escorial research criteria categorize ALS patients based on degree of diagnostic certainty and spread of symptoms. People with “definite” ALS based on clinical presentation tend to have faster progression than those with only “possible” or “probable” ALS. Widespread symptoms also predict faster progression.
Genetic factors
About 10% of ALS cases are directly caused by genetic mutations. Some genetic forms, like those linked to C9orf72, SOD1 and FUS mutations have been associated with faster progression rates. Sporadic ALS linked to no known genetic cause can also demonstrate variable progression rates however.
| Factor | Slow Progression | Fast Progression |
|---|---|---|
| Age of onset | Older age at onset | Younger age at onset |
| Site of onset | Limb onset ALS | Bulbar onset ALS |
| Diagnostic certainty | “Possible” or “probable” ALS | “Definite” ALS |
| Genetics | Sporadic or unknown genetic form | Known familial genetic mutation |
Measuring and predicting progression rate in ALS
Because the clinical course of ALS is so variable, doctors use a variety of methods to measure progression rate and predict outcomes:
ALS Functional Rating Scale (ALSFRS-R)
The ALSFRS-R scale assesses degree of functional impairment in areas like walking, handwriting, speech, swallowing and respiratory function. The rate of decline on the ALSFRS-R over time provides an objective measure of progression rate. Faster dropping scores indicate more rapid advancement.
Forced vital capacity (FVC)
Forced vital capacity (FVC) measures the volume of air a person can forcibly exhale. Declining FVC reflects worsening respiratory muscle weakness. Rapid deterioration of FVC over months can predict faster progression.
Creatine kinase levels
Creatine kinase is an enzyme released with muscle breakdown. Higher blood levels of creatine kinase are associated with faster progression rates in ALS.
Neurofilament light chain
Neurofilament light chain is a protein released by degenerating motor neurons. Elevated levels in blood or CSF appear to correlate with more rapidly advancing ALS. Neurofilament assays may emerge as useful biomarkers to monitor disease progression.
Progression rate formulas
By inputting clinical data like age of onset and site of onset into mathematical models, neurologists can estimate an approximate ALS progression rate for prognostic purposes. Examples include the MiToS formula and Precise ALS calculator.
Can ALS progression slow down over time?
While ALS inevitably leads to worsening disability, the rate of decline is almost never perfectly linear. Periods of faster progression may be followed by plateaus where symptoms temporarily stabilize. However, ALS progression never permanently reverses or significantly slows down long-term. Symptoms may fluctuate day-to-day, but the overall trajectory remains decline.
Periods of temporary stabilization in ALS are likely related to:
- The cyclical, stuttering nature of motor neuron degeneration
- Neurological compensation and remodeling
- Effects of medications like riluzole
- Gaining assistive equipment like wheelchairs and ventilators
- Lifestyle changes to conserve energy and reduce strain
Unfortunately these factors only briefly slow down symptom progression and do not dramatically alter the course of ALS. The steady functional decline inevitably resumes. There are no proven treatments that permanently stop or reverse the progression of ALS.
Examples of slowly progressive ALS cases
To illustrate the variable progression rates in ALS, here are two examples of real-life cases with atypically slow progression:
Case 1: PLS beginning at age 63
A 63 year old man developed progressive walking difficulties due to leg stiffness and spasticity. Weakness was limited to his legs. After 3 years he began using a cane, and after 5 years required a wheelchair for mobility. Mild arm and hand weakness developed 7 years into his disease course, but he remained capable of writing and performing self-care. No muscle atrophy or lower motor neuron signs were observed over 10+ years of gradual progression. This case is consistent with primary lateral sclerosis.
Case 2: Limb onset ALS beginning at age 57
A 57 year old woman noticed the onset of right hand clumsiness along with occasional muscle twitches. Mild right arm and leg weakness and atrophy developed over the next 2 years, causing difficulty with fine motor tasks. Her symptoms spread slowly to involve her left side by year 4. At 6 years from symptom onset she remained capable of slow ambulation and self-care. Her course was slowly progressive compared to typical ALS.
Can early ALS symptoms come and go?
In the earliest stages, subtle symptoms of ALS may seem to fluctuate in severity or disappear for periods of time. For example, early muscle twitching or hand weakness could improve temporarily, giving the false impression that things are getting better. This is likely due to the patchy nature of motor neuron damage early on.
As the disease progresses and more motor neurons are lost, variability in symptoms tends to decrease. Waxing and waning becomes less apparent as deficits become more fixed. Periods of plateaus may still occur, but the overall trajectory is downward. While symptom fluctuations can occur very early on, true reversibility of ALS symptoms does not happen.
What is the life expectancy for slowly progressive ALS?
Life expectancy can be extended in the slow variants of ALS like PLS and PMA compared to more classic ALS. Some studies have found:
- Average survival in PLS may be around 15 years after initial symptoms
- Average survival in PMA may be 10+ years
- In typical ALS, average survival is only 2-5 years
However, prognosis depends greatly on the specific circumstances of each patient. Slowly progressive ALS is still ultimately fatal in most cases. Providing adequate breathing support and nutrition can prolong survival even many years after onset. The course of ALS remains highly variable.
Key points
– While ALS usually involves relatively rapid progression over 2-5 years, slower variants like PLS and PMA do occur in about 10% of cases
– Older age at onset, limb onset symptoms, and less diagnostic certainty predict slower progression on average
– Progression rate can be measured via tools like the ALSFRS-R scale and FVC test
– Periodic plateaus may temporarily slow decline, but ALS progression is never permanently reversed
– Slow forms of ALS allow longer average survival of 10-15 years, but remain incurable
Conclusion
ALS typically causes rapid worsening of muscle weakness and disability over months to a few years. However, in a minority of patients the disease follows a more indolent course spanning many years or even decades before becoming severely disabling. Gradual onset of symptoms and very slow progression is rare but certainly possible in ALS. Accurately measuring the rate of progression and predicting outcomes remains challenging due to the substantial variability between individual patients. While slower progressing forms of ALS provide hope and extend the timeframe for living well with the disease, there are currently no interventions that prevent the steady decline in muscle function and eventual paralysis caused by ALS. Continued research is critically needed to find treatments that substantially slow or halt the progression of all forms of ALS.