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Supplements A Managed Care Perspective on Scientific Advances in Amyotrophic Lateral Sclerosis
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Amyotrophic Lateral Sclerosis: Disease State Overview
Darrell Hulisz, PharmD, RPh
ALS Managed Care Considerations
Briana Santaniello, PharmD, MBA
Participating Faculty

Amyotrophic Lateral Sclerosis: Disease State Overview

Darrell Hulisz, PharmD, RPh
A case-control study by Harrison et al described 36 patients with ALS classified as “ALS reversals” who were compared with 10,723 patients from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database.56 Of the control group, 6352 patients had available family history and demographic data available for comparison. Twenty-three patients were diagnosed with clinically probable lab-supported or clinically probable ALS, 7 with PMA, 4 with definite ALS, and 2 with clinically possible ALS. Twenty patients’ diagnoses were verified by chart review and 16 patients through review of the literature. Reversals were measured by ALSFRS-R gains of at least 4 points, denervation resolution as determined by EMG, and/or improved manual muscle testing strength. When compared with the control group, patients with ALS reversal were more likely to take curcumin, copper, azathioprine, fish oil, vitamin D, and glutathione. However, this finding should not be interpreted as a definite correlation, but as a possible hypothesis for future studies. The authors concluded that although all the patients with ALS reversal did not have El Escorial clinically definite ALS diagnoses, the possibility of ALS was high. They additionally suggested that the patients with ALS reversal may have genetic mutations, leading to disease “reversal” via reinnervation, and whole genome sequencing will be performed to further explore this theory. Studying these patients with reversal may lead to a better understanding of ALS and treatments that delay and ultimately cure the disease.

Best Practices

A patient with ALS wrote, “ALS patients can have a zeal for life rare among patients with other diseases. Shorter life expectancy often spurs patients with ALS to make life experiences and relationships deeper. It is helpful to understand the concept that ‘everyone has a wheelchair,’ and that no one avoids life’s crises forever.”12 This quote is a silver lining in the struggles experienced by patients with ALS. It illustrates that despite patients having to accept the challenges of ALS, they should maximize their potential and time. To assist patients with better management, guidance with best practice recommendations has been developed. The ALS Worldwide guidance includes a multidisciplinary approach to manage symptoms and provide patient support.57 Multidisciplinary team members may include neurologists; pulmonologists; respiratory, occupational, physical, massage, and speech therapists; social workers; nutritionists; support organizations; behavioral health specialists; and pharmacists. According to a review by the Quality Standards Subcommittee of the American Academy of Neurology (AAN), specialized multidisciplinary teams should be considered for patients with ALS to potentially decrease mortality (level B), increase quality of life (level C), and optimize the delivery of healthcare (level B).11 Additionally, the team may support the organization with achieving performance measures developed by the AAN. The measures include developing and updating a multidisciplinary care plan; cognitive and behavioral impairment screening; offering of therapies for ALS symptoms; inquiring about the patient’s respiratory status and referring the patient for pulmonary function testing; screening for impaired nutrition, weight loss, and dysphagia; offering nutritional support; communicating support referral; reviewing disease-modifying pharmacotherapy; discussing noninvasive ventilation treatment with respiratory-insufficient patients; assisting with end-of-life planning; and assessing the patient for falls.58

Neurologists assess, monitor, and treat patients. They are also involved in clinical trials and research that may be beneficial to the patient. The respiratory team, consisting of pulmonologists and respiratory therapists, provides patients with respiratory support because breathing issues are a key symptom in progressive ALS. Occupational therapists are essential to identifying a patient’s challenges with ADLs and assisting them with modifying their current practices or overcoming these challenges. Despite earlier beliefs that exercise damages muscles in patients with ALS, it has been proven to help muscles maintain their power and energy, and the lack of exercise can be harmful. However, patients are usually advised to maintain their current activity level if they are able to do so safely and comfortably.59 Physical therapists are best suited to assist patients with achieving their exercise capacity. Even though massage may be considered a luxury, it is beneficial to both patients and caregivers due to the physical strain of the disease. Caregivers often lift heavy items and regularly shift patients. Because patients are at risk from aspiration due to loss of muscle function, speech therapists not only assist with language, but also assess the patient’s capability to chew and swallow food.

Social workers assist with direction on the navigation of the social services system, end-of life-planning, such as advanced directives, and other available resources, such as transportation and support groups for both the patient and patient’s caregiver. Considering that maintaining adequate nutritional stores and caloric intake is essential to life, nutritionists are key members of the team. Support organizations are available to assist the patient, caregiver, and researcher. Such organizations include the ALS Association, Muscular Dystrophy Association (MDA), and Motor Neurone Disease Association. Psychosocial support, especially from professionals who understand patients with ALS, is beneficial for the patient, patients’ family, and caregiver. The patient may need support making decisions on matters such as making advanced directives. Additionally, the clinic coordinator may assist the patient with the navigation of the medical process, answering questions, collecting information to relay to the respective healthcare professionals, and addressing the patient’s needs and desires.57

The pharmacist is responsible for managing the medication-related aspect of the patient’s care, educating the patient, and assessing the patient’s medication regimen for potential errors, cost savings, adherence, and preference.57 In a study by Jefferies et al, the 2 major interventions performed by a clinical pharmacist participating on a multidisciplinary ALS team were optimizing medication regimens to manage the symptoms of ALS and medication monitoring.60 Additionally, the pharmacist’s interventions allowed more time for the neurologist to focus on neurological complaints. In general, the pharmacists may also be involved in deprescribing, determining the best medication formulations and delivery devices based on the patient’s current level of functioning and physical abilities, and assisting with medication alternatives based on the insurance formularies.

In addition to the items mentioned above, patients may need genetic counseling. Patients with familial ALS may have genetic testing performed. After taking a thorough medical and family history, a genetic counselor will walk the patient through risk evaluation and genetic testing impact.61 The Genetic Information Nondiscrimination Act of 2008 prohibits genetic discrimination from health insurance providers and employers, but not disability, life, and long-term care insurance.62

There are several diseases with symptoms similar to ALS, and most of these conditions are treatable. Because of this, the ALS Association recommends that a person diagnosed with ALS seek a second opinion from an ALS expert—someone who diagnoses and treats many patients with ALS and has training in this medical specialty.33 The ALS Association maintains a list of recognized experts in the field of ALS. Also, local ALS Association chapters or the national office may be contacted. Groups that provide support for patients and research include the ALS Association, the MDA, and the Les Turner ALS Foundation.12

Early diagnosis, participation in clinical trials, being able to identify signs and symptoms, and referral to a multidisciplinary specialty clinic are considered best practices.57 The Centers for Disease Control and Prevention (CDC)’s National Amyotrophic Lateral Sclerosis (ALS) Registry is the only population-based registry in the United States that gathers information for the purpose of studying ALS.63 Goals of the registry include estimating the incidence and prevalence of ALS, studying risk factors associated with ALS, and providing a database for research to improve the care of patients with ALS.64 The registry collects information, such as gender, age, physical activity, family history, military service information, work history, and environmental and occupational risk factors.64 In addition to collecting survey information, the CDC collects and stores the biological samples of the National ALS Registry patients in the National ALS Biorepository.65 The type of biological samples collected includes proteins, blood, DNA, urine, cells, and tissue.65 The collection also includes a postmortem component involving the collection of bone, brain, skin, spinal cord, muscle, and cerebral spinal fluid.65 Informing patients about these registries and the impact of their involvement on the future of ALS may lead to discovery of more about various aspects of ALS, such as improved knowledge and treatments.


ALS is a devastating disease. It is difficult to diagnose, debilitating, and has a short survival and poor prognosis for most patients. Unfortunately, there is currently no cure. With the invention of DNA technology, several potential therapy targets have been identified. Through the advancements of medicine and voluntary enrollment of patients with ALS into registries, a better understanding of ALS and therapies will ensue. In the interim, patients should be referred to a multidisciplinary team who will assist them, their families, and caregivers with managing the disease.

Author affiliation: Associate Professor, Department of Family Medicine, Case Western Reserve University School of Medicine; Clinical Pharmacy Specialist, University Hospitals Medical Group, Cleveland, OH.
Funding source: This activity is supported by educational funding provided by Mitsubishi Tanabe Pharma America, Inc. 
Author disclosure: Dr Hulisz has no relevant financial relationships with commercial interests to disclose.
Authorship information: Concept and design; critical revision of the manuscript for important intellectual content; and administrative, technical, or logistic support.
Address correspondence to:
Dr Hulisz gratefully acknowledges Kisha O’Neal Gant, PharmD, for her contributions to the development of this article. 
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