Written By Sahasra Thridandapani
Disease Overview
Amyotrophic Lateral Sclerosis (ALS), often referred to as Lou Gehrig's disease, is a neurodegenerative disorder that impacts the nerve cells in the brain and spinal cord. It represents the most common motor neuron disease in adults, with an average of 1–2.6 cases per 100,000 a year. The disease primarily manifests in individuals aged 58–60 years, with an average survival from onset to death of 3–4 years. In the USA alone, 12,187 prevalent cases were diagnosed between October 19, 2010, and December 31, 2011. Sporadic ALS includes 90–95% of cases, while 5–10% are familial ALS. ALS diagnosis relies on clinical evaluation and is usually more prominent in an individual’s seventies. Though this is a progressive disease without a cure, understanding the manifestations and causes can help better understand how to manage its symptoms.
FALS & SALS
Familial Amyotrophic Lateral Sclerosis (FALS) and Sporadic Amyotrophic Lateral Sclerosis (SALS) represent two distinct categories of the same neurodegenerative disorder, ALS. FALS comprises 5-10% of all ALS cases. It exhibits a clear hereditary pattern that has been passed along down generations. Specific genetic mutations, such as SOD1, C9ORF72, and FUS, are transmitted within families, contributing to the clustering of ALS cases. The onset of FALS symptoms varies in age, and disease progression differs among affected family members. Despite its hereditary nature, the prognosis for FALS is similar to sporadic cases, with an average survival from onset to death ranging between 3 to 5 years. On the other hand, Sporadic ALS (SALS) comprises 90-95% of ALS cases, occurring without a familial history of the disease. SALS is characterized by genetic complexity, lacking a clear hereditary pattern. Recent research suggests a contribution from a combination of genetic susceptibility and environmental factors in SALS development with an onset to death similar to FALS.
Risk of Advances in Genetic Markers:
Superoxide Dismutase 1 (SOD1) is a key genetic marker in ALS, discovered in 1993 and studied by Chio Rosen and Millecamps. 12-20% of FALS and 1-2% of ` SALS are associated with the SOD1 genome. SOD1, an antioxidant enzyme, neutralizes harmful radicals generated during cellular metabolism. In ALS, SOD1 mutations lead to a toxic gain of function, configuring the protein’s normal function, and leading to motor neuron degeneration. Another gene mutation that results in FALS and SALS is the C9ORF72 gene mutation. The C9ORF72 gene undergoes an abnormal expansion of a hexanucleotide repeat sequence. This expanded repeat leads to the production of abnormal FNA and protein products that are thought to lead to toxicity, disrupting cellular functions and contributing to motor neuron degeneration.
Signs & Symptoms of ALS
Many signs and symptoms can hint at the early progression of ALS in an individual. An example includes troubled walking due to muscle weakness. Since ALS causes a gradual loss of motor neurons individuals with ALS may experience difficulty lifting their feet, maintaining balance, and coordinating movements. Some individuals may develop spasticity which results in muscle stiffness and involuntary muscle contractions. Another example is difficulty swallowing and slurred speech also known as dysphagia and dysarthria, respectively. Since ALS, degrades both upper (head) and lower (spine) motor neurons, the motor neutrons control voluntary muscle movements, including speech and swallowing. The Bulbar region, which includes the muscles responsible for speech and swallowing, is affected leading to slurred speech or difficulty articulating words. Furthermore, the muscles of the tongue, lips, vocal cords, and jaw are affected, leading to changes in speech quality. Individuals with ALS may have difficulty directing food and liquids from the mouth to the stomach, leading to a risk of choking and aspiration (inhaling food or liquid into the airways). Lastly, thinking and behavioral changes are highly prominent in individuals with ALS. For example, in some ALS cases, particularly those associated with mutations in the C9ORF72 gene, individuals may develop Frontotemporal Dementia (FTD). FTD can result in changes in personality, social behavior, and executive function.
Diagnostic Procedures
Many procedures can be done to detect ALS. An electromyogram (EMG) can detect abnormalities in the electrical activity of muscles, which can help figure out the impact of motor neuron degeneration on muscle function. A specific type of EMG is a Meedle EMG, in which fine needle electrodes are inserted into the muscles being tested. These electrodes record the electrical activity of the muscle during contraction and at rest. During the process, if fasciculations (involuntary muscle twitches) and fibrillations are present then it is a sign of motor neuron dysfunction. Along with EMG, nerve conduction study measures a nerve’s ability to send impulses to muscles in different areas to detect nerve damage. Another diagnostic procedure that can be done is an MRI (Magnetic Resonance Imaging). An MRI produces images of the brain and spinal cord by using radio waves and electromagnetic fields. It can reveal conditions such as herniated disks or spine tumors that can lead to ALS symptoms and presence. Another procedure that can be done is a spinal tap, also known as a lumbar puncture, in which spinal fluid is removed using a small needle between 2 vertebrae to remove CSF (cerebrospinal fluid). Protein levels are analyzed from the CSF and the detection of proteins such as neurofilament proteins can prove the presence of ALS.
Treatments/Procedures
Riluzole
Since ALS is an incurable condition, treatment can only be done to slow the progression of the condition. According to the Food and Drug Administration, Riluzole including Rilutek, Exservan, and Tiglutik has been approved as a medication for ALS. This medication can increase life expectancy by 25%. This medication is known to regulate the activity of the neurotransmitter glutamate. In ALS, there is a presence of increased glutamate in the synaptic spaces around the motor neurons. Excessive glutamate can lead to excitotoxicity, where overstimulation of neurons can lead to cell damage, so Riluzole can help regulate this. Furthermore, riluzole has antioxidative properties which can reduce oxidative stress caused by ALS.
Sodium phenylbutyrate-taurursodiol (Relyvrio)
Relyvrio can reduce the functional decline of ALS by 25% according to the FDA. Endoplasmic Reticulum (ER) stress has been proven to be regulated using sodium phenylbutyrate. The accumulation of misfolded proteins from ALS is treated by Relyrio via its protective effect on neurons. Misfolded proteins can contribute to the formation of aggregates in ALS. Improving protein folding may reduce the burden of misfolded proteins.
Breathing Care:
As muscles weaken due to ALS, breathing becomes more troubling. Therefore, breathing care helps maintain and support respiratory function as long as possible from complications such as pneumonia and other respiratory infections. A specific type of intervention used is a non-invasive ventilation (NIV) device such as a bilevel positive airway pressure (BiPAP) machine. This machine can help improve oxygenation levels which is essential for one’s overall being. Another type of device includes a cough assist device. Due to the weakened respiratory muscle, one’s ability to cough can be impaired leading to infections. Therefore, this device can generate a cough to clear the airways.
Physical Therapy
Physical Therapy is part of a comprehensive care plan for ALS patients who are undergoing motor neuron degradation and muscle weakness/atrophy. Some key aspects of physical therapy include range of motion exercises and adaptative equipment/assistive devices. Range of motion exercises help prevent joint stiffness and maintain flexibility in muscles and joints by adapting to an individual's abilities. Furthermore, assistive equipment such as mobility aids, braces, wheelchairs, or any other devices that can enhance independence help facilitate daily activity in ALS patients.
Riluzole Experiment Results
As we have established, ALS is a noncurable disease, but some treatments, like those listed above, can be effective in minimizing the progression and severity of the clinical manifestation. As seen in this treatment groups vs placebo experiment, the percentage of patients remaining in stage 4, following this experiment, has significantly declined. Leaving behind the complexity of the placebo concept, in general, patients suffering from stage 4 have seen some hope and prolongment of their state of being.
Lifestyle Modifications
Nutrition and Swallowing Management: Working with dieticians and speech therapists can help assess individual nutritional needs and provide guidance on dietary choices. One needs to constantly monitor their caloric intake to prevent any unintentional weight less. This is essential to maintaining overall health, especially in a more severe stage of ALS.
Communication Strategies: As communicative strategies are hindered due to the progression of ALS, alternative communication methods such as text-to-speech devices can help slowly regain the function of expression.
Emotional and Psychological Support: Suddenly being told that one is suffering from a terminal illness can destroy oneself. During these dire times, it's important for the patients to stay in touch with their emotions and cope with the emotional challenges by seeking support from mental health professionals, support groups, etc.
Works Cited
ALS (Amyotrophic Lateral Sclerosis) | Brain Institute | OHSU. (n.d.). Www.ohsu.edu. https://www.ohsu.edu/brain-institute/als-amyotrophic-lateral-sclerosis
Aschenbrenner, D. S. (2023). New Drug Approved For ALS. AJN, American Journal of Nursing, 123(1), 22–23. https://doi.org/10.1097/01.naj.0000911516.31267.67
Belzil, V. V., Valdmanis, P. N., Dion, P. A., Daoud, H., Kabashi, E., Noreau, A., Gauthier, J., Hince, P., Desjarlais, A., Bouchard, J.-P. ., Lacomblez, L., Salachas, F., Pradat, P.-F. ., Camu, W., Meininger, V., Dupre, N., & Rouleau, G. A. (2009). Mutations in FUS cause FALS and SALS in French and French Canadian populations. Neurology, 73(15), 1176–1179. https://doi.org/10.1212/wnl.0b013e3181bbfeef
Cucovici, A., Fontana, A., Ivashynka, A., Russo, S., Renna, V., Mazzini, L., Gagliardi, I., Mandrioli, J., Martinelli, I., Lisnic, V., Muresanu, D. F., Zarrelli, M., Copetti, M., & Leone, M. A. (2021). The Impact of Lifetime Alcohol and Cigarette Smoking Loads on Amyotrophic Lateral Sclerosis Progression: A Cross-Sectional Study. Life, 11(4), 352. https://doi.org/10.3390/life11040352
Fang, T., Al Khleifat, A., Meurgey, J.-H., Jones, A., Leigh, P. N., Bensimon, G., & Al-Chalabi, A. (2018). Stage at which riluzole treatment prolongs survival in patients with amyotrophic lateral sclerosis: a retrospective analysis of data from a dose-ranging study. The Lancet Neurology, 17(5), 416–422. https://doi.org/10.1016/s1474-4422(18)30054-1
Mayo Clinic Staff. (2019, August 6). Amyotrophic Lateral Sclerosis (ALS) - Symptoms and Causes. Mayo Clinic; Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/amyotrophic-lateral-sclerosis/symptoms-causes/syc-20354022
PhD, L. F. (n.d.). Living with ALS - ALS News Today. https://alsnewstoday.com/living-with-als/
Roggenbuck, J., Quick, A., & Kolb, S. J. (2017). Genetic testing and genetic counseling for amyotrophic lateral sclerosis: an update for clinicians. Genetics in Medicine, 19(3), 267–274. https://doi.org/10.1038/gim.2016.107
SOD1 - an overview | ScienceDirect Topics. (n.d.). Www.sciencedirect.com. Retrieved December 31, 2023, from https://www.sciencedirect.com/topics/neuroscience/sod1#:~:text=Mutations%20in%20the%20gene%20for
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