Progression of ALS
ALS is by definition a progressive disorder that involves degeneration of the motor system at all levels. Although there are no available objective measures of disease progression, the rate of progression can be assessed using an outcome measure called the "ALS Functional Rating Scale Revised (ALSFRS-R)", a 12-item instrument administered as a clinical interview or patient-reported questionnaire that produces a score between 48 (normal function) and 0 (severe disability) (Cederbaum et al., 1999). Currently, this is the standard way to stage the severity of function of patients throughout the country. However, in 2012, Roche et al. proposed a universal and objective measure of disease progression that sought to define easily identified clinical milestones that could be shown to occur at specific points in the disease course, reflect disease progression and impact prognosis and treatment. Therefore, they proposed the following simple staging system for ALS:
However, this system is only partially validated so far and the order and rate of symptom progression varies greatly from person to person. According to the ALS association, at the onset of ALS the symptoms may be so slight that they are frequently overlooked. With regard to the appearance of symptoms and the progression of the illness, the course of the disease may include the following:
For patients with initial bulbar symptoms, progression is faster and prognosis is poorer due to the increased risk of aspiration and pneumonia. These patients typically have 3 years mean duration as compared to 5 years for limb onset patients. In addition, progression tends to be slower in patients who are younger than 40 at onset (Sabatelli et al., 2008). However, for patients in later stages of the disease, difficulty in chewing and swallowing increases the risk of choking or of aspirating food into the lungs. Aspiration pneumonia can develop, and maintaining a healthy weight can become a significant problem that may require the insertion of a feeding tube. As the diaphragm and intercostal muscles of the rib cage that support breathing weaken, measures of lung function such as vital capacity and inspiratory pressure diminish. At this point, some patients choose palliative hospice care as most people with ALS die of respiratory failure or pneumonia. Although respiratory support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Most people with ALS die from respiratory failure, usually within three to five years from the onset of symptoms. The median survival time from onset to death is around 39 months, and only 4% survive longer than 10 years (Turner et al., 2003). For a detailed analysis of the progression of dysarthria in ALS, please see the Dysarthria section.
References:
Cederbaum, J.M., Stambler, N., Malta, E., Fuller, C., Hilt, D., Thurmond, B., & Nakanishi, A. (1999). The ALSFRS-R: A revised ALS functional rating scale that incorporates assessments of respiratory function. Journal of Neurological Science, 169(1-2), 13-21.
Roche, J.C., Rojas-Garcia, R., Scott, K.M., Scotton, W., Ellis, C.E., Burman, R., Wijesekera, L., Turner, M.R., Leigh, P.N., Shaw, C.E., & Al-Chalabi, A. (2012). A proposed staging system for amyotrophic lateral sclerosis. Brain, 136(11), 2-24.
Sabatelli, M., Madia, F., Conte, A., Luigetti, M., Zollino, M., Mancuso, I., Monaco, M., Lippi, & G., Tonali, P. (2008). Natural history of young-adult amyotrophic lateral sclerosis. Neurology, 71(12), 876-881.
Symptoms. alsa.org. Retrieved November 22, 2013, from http://alsa.org.
Turner, M.R., Parton, M.J., Shaw, C.E., Leigh, P.N., & Al-Chalabi, A. (2003). Prolonged survival in motor neuron disease: A descriptive study of the King's database 1990-2002. Journal of Neurology, Neurosurgery, and Psychiatry, 74(7), 995-997.
- Stage 1: Symptom onset (involvement of first region).
- Stage 2A: Diagnosis.
- Stage 2B: Involvement of a second region.
- Stage 3: Involvement of a third region.
- Stage 4A: Need for gastrostomy.
- Stage 4B: Need for respiratory support (non-invasive ventilation).
However, this system is only partially validated so far and the order and rate of symptom progression varies greatly from person to person. According to the ALS association, at the onset of ALS the symptoms may be so slight that they are frequently overlooked. With regard to the appearance of symptoms and the progression of the illness, the course of the disease may include the following:
- muscle weakness in one or more of the following: hands, arms, legs or the muscles of speech
- swallowing or breathing
- fasciculations and cramping of muscles, especially those in the hands and feet
- impairment of the use of the arms and legs
- "thick speech" and difficulty in projecting the voice
- in more advanced stages, shortness of breath, difficulty in breathing and swallowing
For patients with initial bulbar symptoms, progression is faster and prognosis is poorer due to the increased risk of aspiration and pneumonia. These patients typically have 3 years mean duration as compared to 5 years for limb onset patients. In addition, progression tends to be slower in patients who are younger than 40 at onset (Sabatelli et al., 2008). However, for patients in later stages of the disease, difficulty in chewing and swallowing increases the risk of choking or of aspirating food into the lungs. Aspiration pneumonia can develop, and maintaining a healthy weight can become a significant problem that may require the insertion of a feeding tube. As the diaphragm and intercostal muscles of the rib cage that support breathing weaken, measures of lung function such as vital capacity and inspiratory pressure diminish. At this point, some patients choose palliative hospice care as most people with ALS die of respiratory failure or pneumonia. Although respiratory support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Most people with ALS die from respiratory failure, usually within three to five years from the onset of symptoms. The median survival time from onset to death is around 39 months, and only 4% survive longer than 10 years (Turner et al., 2003). For a detailed analysis of the progression of dysarthria in ALS, please see the Dysarthria section.
References:
Cederbaum, J.M., Stambler, N., Malta, E., Fuller, C., Hilt, D., Thurmond, B., & Nakanishi, A. (1999). The ALSFRS-R: A revised ALS functional rating scale that incorporates assessments of respiratory function. Journal of Neurological Science, 169(1-2), 13-21.
Roche, J.C., Rojas-Garcia, R., Scott, K.M., Scotton, W., Ellis, C.E., Burman, R., Wijesekera, L., Turner, M.R., Leigh, P.N., Shaw, C.E., & Al-Chalabi, A. (2012). A proposed staging system for amyotrophic lateral sclerosis. Brain, 136(11), 2-24.
Sabatelli, M., Madia, F., Conte, A., Luigetti, M., Zollino, M., Mancuso, I., Monaco, M., Lippi, & G., Tonali, P. (2008). Natural history of young-adult amyotrophic lateral sclerosis. Neurology, 71(12), 876-881.
Symptoms. alsa.org. Retrieved November 22, 2013, from http://alsa.org.
Turner, M.R., Parton, M.J., Shaw, C.E., Leigh, P.N., & Al-Chalabi, A. (2003). Prolonged survival in motor neuron disease: A descriptive study of the King's database 1990-2002. Journal of Neurology, Neurosurgery, and Psychiatry, 74(7), 995-997.