11.18.2024

Amyotrophic Lateral Sclerosis (ALS) – Wrangling the Symptom Management Rodeo

INTRODUCTION1-4

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a rare, incurable, progressive neurodegenerative disease that directly affects the motor neuron system (muscles involved in swallowing, speaking, breathing, and ambulation).5 An estimated 5,600 persons in the United States are diagnosed with ALS each year, with annual incidence rates at 2 – 3 persons per 100,000 population. This is the same number of persons diagnosed with multiple sclerosis and 5 times higher than Huntington’s disease.

There are two types of ALS:

  • Sporadic ALS has a median age of onset of 65 years and 90% of the cases present with no known family history or presence of a genetic mutation.
  • Familial ALS is associated with a gene mutation and has a median age of onset of 50 years, with 5% to 10% of the cases having a known family history of ALS. There is a 50% chance each offspring will inherit the gene mutation and may develop the disease.

SIGNS AND SYMPTOMS

People with ALS progressively lose control of their muscles with weakness as the most common first symptom. Not all persons with ALS experience the same symptoms or sequence of progression, but all persons with ALS (PALS) will experience progressive muscle weakness and paralysis.

Early symptom onset is characterized in one of two ways:6

  • Limb onset ALS, the most common type, is when initial symptoms begin in the muscles that control the legs, feet, arms and hands (e.g., tripping, dropping things).
  • Bulbar onset ALS, making up one-third of ALS diagnoses, is when symptoms begin in the face or neck.7 It is described as weakness, affecting the muscles that control swallowing or speech, leading to trouble swallowing (dysphagia), slurred speech, and changes in vocal pitch.

Dysphagia, poor appetite, and/or difficulty self-feeding due to arm weakness in ΑLS leads to insufficient caloric and fluid intake resulting in weight loss, worsened weakness, and fatigue. Dysphagia also increases the risk for aspiration and choking. When weight loss or dysphagia are evident, patients should be referred to a speech language pathologist and nutritionist who can recommend high-calorie and high-protein nutritional supplements, food and liquid consistency modifications, and safer swallowing techniques. Indications for the need of an enteral tube for feeding also need to be assessed.8,9

Muscle cramps, spasticity (stiff muscles) and twitching (fasciculations) affecting the tongue and limbs may also be present early in the disease process. Other symptoms occurring in early to mid-disease include:

  • Drooling (sialorrhea) – Saliva is produced by the salivary glands in response to stimuli such as the sight and/or smell of food. Those with ALS continue to produce the same amount of saliva, but as ALS progresses, they lose their ability to swallow, causing saliva to pool in the mouth with resultant drooling. While drooling may cause skin irritation and embarrassment, aspirating saliva can also precipitate choking or pneumonia, a leading cause of death for ALS patients.7
  • Fatigue – Fatigue is reported in approximately 90 percent of PALS. Fatigue due to hypoventilation may improve with noninvasive ventilation such as bilevel positive airway pressure (BPAP) delivered via a BiPAP® machine. Fatigue may be associated with riluzole, a medication used to treat ALS, but is more commonly a manifestation of the effort required to perform daily activities.8
  • Pseudobulbar affect (PBA) – PBA is characterized by involuntary, sudden and frequent episodes of laughing and/or crying that do not match the patient’s mood. It is thought to result from structural damage to sensory and motor neurons.10

As ALS progresses, symptoms can include shortness of breath and difficulty breathing (dyspnea) and cognitive impairment (often underdiagnosed):

  • Dyspnea – Early symptoms of respiratory insufficiency include οrthοрnеa, morning headache, daytime fatigue, and difficulty breathing on exertion. This happens when the muscles involved in respiration are affected. First-line treatment is BPAP for patients who tolerate it. The need for permanent ventilatory support is inevitable to assist with breathing as the disease progresses however and may include tracheostomy.10
  • Frontotemporal dementia (FTD) – Persons with ALS (PALS) have an increased incidence of FTD, a form of dementia characterized by symptoms of apathy, difficulties planning and organizing, and often either behavioral disturbances or language impairment. Since many PALS develop severe dysarthria and impaired motor function affecting ability to write, it is sometimes difficult to fully assess cognitive function in advanced stages. It is estimated that up to 30 percent of PALS have cognitive impairments in planning and organizing while not meeting criteria for dementia while up to 15 percent do meet criteria for FTD.10

Other symptoms as ALS progresses include inability to stand, walk or get out of bed. Since ALS only affects motor neurons, the senses of taste, smell, sight, hearing and touch are not affected. For many PALS, the muscles of the eyes and bladder are also not affected.11

SYMPTOM MANAGEMENT

In 2020, Brizzi KT, et al published the results of a survey of 764 persons with ALS (PALS) and 378 caregivers of living persons with ALS (C-LPALS).12 The aim of the study was to elicit perspectives about the biggest challenges of living with ALS, feedback on care, and priorities for clinical research. The data captured the most common symptoms experienced with weakness, fatigue, and problems with speech as the top 3 symptoms for PALS.

Symptom priorities of ALS at end of life are reportedly different than those described by Brizzi KT, et al. According to an article by Sethi A (2022), the most prominent symptoms of ALS during late stages are dyspnea, anxiety and secretions.6,13

PHARMACOTHERAPY

There are four medications currently approved by the FDA for treatment of ALS.14 Of these, riluzole may be the most familiar. The data supporting the outcomes of these medications is not encouraging. Consider discontinuing treatment that is neither curative, nor palliative. Riluzole may be safely discontinued abruptly without causing withdrawal symptoms. It is unclear if the same holds true for the other 3 agents. Discontinuation of any of the disease-modifying therapies below may decrease the risk of adverse effects and potential drug interactions.5,15

A combination of pharmacologic and non-pharmacologic approaches to symptom management in ALS may provide the most benefit. The below table provides a summary of interventional strategies to manage common symptoms.4,13,14,16 Some non-pharmacologic interventions may not be conducive with patients’ goals of care. Assess for appropriateness before recommending.

CAREGIVER SUPPORT

Persons with ALS need 24/7 support. It is important that caregivers providing that support are equipped with resources on understanding the disease and how to navigate and prepare for what’s ahead. Organizations like the ALS Association provide educational resources along with access to local and online support groups that celebrate networking amongst other caregivers.17

KEY TAKEAWAYS

ALS is a rare, terminal, progressively degenerative disease affecting the muscles involved in swallowing, speaking, breathing, and ambulation. Disease-modifying therapies, such as riluzole, provide little benefit at the end of life and may contribute to medication burden, adverse effects and drug interactions. Medical management should prioritize the most bothersome symptoms at this stage including dyspnea, anxiety, and sialorrhea. Most patients with ALS succumb to respiratory failure while enrolled in hospice and it is not uncommon for some to deteriorate suddenly.9 A multimodal approach to care including symptom management, non-pharmacologic interventions, psychosocial, spiritual, and practical support to both patients and their caregivers prove the most beneficial to achieve comfort goals.8

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REFERENCES

  1. ALS Association. Understanding ALS. Accessed Nov 12, 2024. Available from: als.org/understanding-als.
  2. Adiao KJ, et al. Efficacy and safety of mexiletine in amyotrophic lateral sclerosis: A systematic review of randomized controlled trials. Neurodegener Dis Manag. 2020 Dec;10(6):397-407. https://doi.org/10.2217/nmt-2020-0026
  3. Armon C. Amyotrophic Lateral Sclerosis. In: Medscape Drugs & Diseases: Neurology. Talavera F, (ed), (Accessed Nov 12, 2024). Available from: https://emedicine.medscape.com/article/1170097-overview
  4. Houseman G, Kelley M. palliative care for patients in the USA with amyotrophic lateral sclerosis: Current challenges. Nursing: Research and Reviews. 2015:5 119–127. https://doi.org/10.2147/NRR.S77066
  5. Scott K, Shannon R, Roche-Green, et al. Pharmacologic Management Strategies in ALS. In: Palliative Care Network of Wisconsin Fast Facts. Nov 30, 2023. https://www.mypcnow.org/fast-fact/pharmacologic-management-strategies-in-als/
  6. Muscular Dystrophy Association. Amyotrophic Lateral Sclerosis Fact Sheet. Accessed Nov 12, 2024. Available from: https://www.mda.org/sites/default/files/2024/04/ALS-Fact-Sheet.pdf
  7. Scott K, Shannon R, Roche-Green A. Fast Facts, and Concepts #299. Management of sialorrhea in ALS. Nov 11, 2024. https://www.mypcnow.org/fast-fact/management-of-sialorrhea-in-als/
  8. Galvez-Jimenez N, Quinn C. Symptom-based management of amyotrophic lateral sclerosis. In: UpToDate, Shefner JM, Morrison RS, Goddeau RP, (Eds), (Accessed Nov 12, 2024).
  9. Frydman JL, Pedowitz E, Lindenberger E. Nutrition for Patients with Amyotrophic Lateral Sclerosis (ALS). Nov 11, 2024. Available from: https://www.mypcnow.org/fast-fact/nutrition-for-patients-with-amyotrophic-lateral-sclerosis-als/
  10. Ahmed A, et al. Pseudobulbar affect: Prevalence and management. Ther Clin Risk Manag. 2013;9:483-489. https://doi.org/10.2147/TCRM.S53906
  11. ALS Association. Understanding ALS: ALS symptoms and diagnosis. Accessed Nov 12, 2024. Available from: https://www.als.org/understanding-als/symptoms-diagnosis
  12. Brizzi KT, Bridges JFP, Yersak J, et al. Understanding the needs of people with ALS: A national survey of patients and caregivers. Amyotroph Lateral Scler Frontotemporal Degener. 2020;21(5-6): 355-363. https://doi:10.1080/21678421.2020.1760889.
  13. Sethi A. Everett E, Mehta A, et.al. The role of specialty palliative care for amyotrophic lateral sclerosis. Am J Hosp Palliat Care 2022;39(7):865-873.https://doi:10.1177/10499091211049386.
  14. Clinical Pharmacology [database online]. Tampa, FL: Elsevier/Gold Standard, Inc.; 2024.
  15. Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev. 2012;(2); CD000147. https://doi:10.1002/14651858.CD001447
  16. Thompson E. Pharmacist considerations for treating patients with ALS. S. Pharmacist. Aug 19, 2019. Available from: https://www.uspharmacist.com/article/pharmacist-considerations-for-treating-patients-with-als
  17. org. Resources for Caregivers. Accessed Nov 12, 2024. Available from: https://www.als.org/navigating-als/for-caregivers/caregiver-resources

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