Amyotrophic Lateral Sclerosis (ALS): Definition, Disease Progression and Prognosis

1. National Hospice and Palliative Care Organization’sPalliative Care Resource SeriesPalliative Care in ALSWritten by: Mara Lugassy, MDHospice Medical DirectorMJHS Hospice and Palliative CareAssistant ProfessorDepartment of Family and Social MedicineAlbert Einstein College of Medicine

2. Amyotrophic Lateral Sclerosis (ALS): Definition, Disease Progression and Prognosis • Progressive fatal neurodegenerative disorder • Destruction of upper and lower motor neurons in brain and spinal cord • Upper motor neuron: spasticity, clonus, hyperreflexia • Lower motor neurons: weakness, atrophy, fasciculation • No known cure

3. ALS: Definition, Disease Progression and Prognosis • 80% limb onset; 20% bulbar onset • Progressive involvement all limbs and axial muscles • Progressive impairment oral, pharyngeal and respiratory muscles • Loss of ability to speak, swallow and breathe • Complete dependency for ADLs and near total paralysis • Relative sparing of extraocular movements and bladder/bowel function • Death from respiratory failure Tiryaki E, Horak H. ALS and Other Motor Neuron Disease. Continuum. Vol 20(5). Oct. 2014. 1185-1207

4. ALS: Definition, Disease Progression and Prognosis • Median survival 3-5 years • Highly variable survival times • Prognosis can be modified to some degree by treatment options • Approximately 10% of patients with ALS survive >10 years • Predictors of poorer prognosis: • Older age • Bulbar onset • More rapid progression in early stages of disease Chio A, Logroscino G, Hardiman O, et al. Prognostic factors in ALS: A critical review. Amyotroph Lateral Scler. 2009 ; 10(5-6): 310–323

5. Palliative Care in ALS • Multifaceted role: • Symptom control • goals of care discussions • patient and family support • assistance with transitions of care • Recent RTC demonstrating improvements in quality of life and symptom burden in ALS and other neurodegenerative diseases with early referral to specialist level palliative care Veronese S, Gallo G, Valle A, et al. Specialist palliative care improves the quality of life in advanced neurodegenerative disorders: NE-PAL, a pilot randomised controlled study. BMJ Support Palliat Care. 2015 Jul 16.

6. Palliative Care in ALS • A collaborative effort • Important role for multiple disciplines throughout disease course • Multidisciplinary ALS clinics: • Early access to specialist therapies • improved coordination of care • Increased median survival (19 months vs. 11 months in retrospective review of 417 patients) • Improvement in quality of life Aridegbe T, Kandler R, Walters SJ, et al. The natural history of motor neuron disease: assessing the impact of specialist care. Amyotroph Lateral Scler Frontotemporal Degener 2013; 14:13-19. Van den Berg JP, Kalmijn S, Lindeman E, et al. Multidisciplinary ALS care improves quality of life in patients with ALS. Neurology. 2005 Oct 25;65(8)1264-7.

7. Multi-disciplinary ALS Care • Physician (neurologist, palliative care, gastroenterologist) • Nurse • Social worker • Occupational/Physical therapist • Speech and Language Pathologist • Respiratory Therapist • Dietitian • Psychologist

8. Disease Modifying Pharmacotherapy - Riluzole • Glutamate inhibitor • Only medication approved for treatment of ALS • Prolongs survival (or time to tracheostomy) by 2-3 months • Modest slowing of decline in limb and bulbar function • Does not reverse or improve existing symptoms • No evidence regarding impact on quality of life • Side effects: GI symptoms, fatigue • Monitor LFTs Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev 2012; 3:CD001447.

9. Symptom Management • Sialorrhea • Thickened secretions • Pain • Muscle Cramps • Spasticity • Pseudobular affect

10. Symptom Management: Sialorrhea • Excessive drooling • Can be managed by: • minimization of sweet and sour foods which stimulate the salivary glands • use of suction devices • pharmacotherapy, including tricyclic antidepressants and anticholinergic medications. • Botulinum toxin and radiation therapy may provide benefit in cases of severe drooling.

11. Symptom Management: Thickened Secretions • Difficulty with expectoration and mucous plugging • May be exacerbated by anticholinergic medications used to treat sialorrhea. • Thickened secretions can be managed by: • Increasing fluid intake • Air humidification • Use of mucolytics, including guaifenesin and N-Acetyl cysteine. • Expectoration of secretions can also be facilitated by use of a cough assist device.

12. Symptoms: Pain • Significant impact on quality of life • Musculoskeletal • Immobility • Atrophy • Increased pressure on bones and joints • Interventions • Attention to positioning and repositioning • Gentle stretching and range of motion activities • Analgesics: acetaminophen, NSAIDS, opioids

13. Symptoms: Muscle Cramps • Occur in up to 95% • Stretching, positioning, massage • Limited evidence: • Antiepileptics (levetiracetam, phenytoin, carbamazepine) • Benzodiazepines • Baclofen • Quinine – no longer recommended due to risk of toxicities • Mexiletine • Recent phase II randomized controlled study: reduction in cramp frequency and intensity Weiss MD, Macklin EA, Simmons Z, et al. Mexiletine ALS Study Group. A randomized trial of mexiletine in ALS: Safety and effects on muscle cramps and progression. Neurology 2016 Apr 19;86(16):1474-81. Caress JB, Ciarlone SL, Sullivan EA et al. Natural history of muscle cramps in amyotrophic lateral sclerosis. Muscle Nerve. 2016 Apr;53(4):513-7

14. Symptoms: Spasticity • Can result in pain, contractures, falls • Interfere with care • Stretching, positioning, massage • Muscle relaxants • Baclofen, tizanidine • May worsen weakness

15. Symptoms: Pseudobulbar Affect • Sudden uncontrollable outbursts of laughter or crying • Degeneration of corticobulbar tracts • Occurs in multiple neurologic conditions • Leads to embarrassment, social isolation, associated with reduced quality of life • Can be mistaken for depression

16. Symptoms: Pseudobulbar Affect • Interventions: • Education of patients and families • Dextromethorphan-quinidine (20 mg/10 mg) • Tricyclic antidepressants, SSRIs Brooks BR, Thisted RA, Appel SH, et al. Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial. Neurology. 2004;63(8):1364. Rix Brooks B, Crumpacker D, Fellus J, et al. PRISM: A novel research tool to assess the prevalence of pseudobulbar affect symptoms across neurologic conditions. PLoS One. 2013; 8(8): e72232

17. Cognitive Impairment • Occurs in approximately 50% of patients with ALS • Ranges from subtle findings to dementia • Deficits in executive function • Memory relatively preserved • Frontotemporal dementia in 15% • Need to consider capacity in medical decision making/goals of care discussions

18. Communication Deficits • Dysarthria progressing to total loss of speech • Significant impact on quality of life • Source of emotional distress • Compensatory Strategies • Minimize distractions • Slowing of speech • Over articulation (pronounce each sound) • Listener repeats understood words Körner S, Sieniawski M, Kollewe K, et al. Speech therapy and communication device: impact on quality of life and mood in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2013 Jan;14(1):20-5.

19. Augmentative/Alternative Communication • Augmentative communication: supports or supplements impaired speech • Ex. Voice amplifier in hypophonia • Alternative communication: used in the absence of speech • Ex. Letter board • Needs change as disease progresses • Early use can improve quality of life and mood in patients and caregivers Londral A, Pinto A, Pinto S, Azevedo L, De Carvalho M. Quality of life in amyotrophic lateral sclerosis patients and caregivers: Impact of assistive communication from early stages. Muscle Nerve. 2015;52(6):933

20. ALS and Nutrition • Significant source of concern for patients and caregivers • Multiple barriers • Physical impairment to feeding (arm weakness) • Progressive dysphagia • Fear of choking • Extensive time and energy devoted to obtaining adequate nutrition • BMI <18.5 associated with shorter survival Karam C, Paganoni S, Joyce N et al. Palliative care issues in amyotrophic lateral sclerosis: an evidence-based review. American Journal of Hospice and Palliative Medicine. 2016 vol 33(1)84-92.

21. ALS and Nutrition: Dysphagia and Nutrition Management • Involvement of nutritionist and speech/swallowing therapist • Modification of food consistency • Add thickener to liquids • Puree solid foods • Multiple swallows with each bite • Avoid distractions while eating • Chin tuck and other techniques • Addition of calorie rich foods • Oral supplements

22. ALS and Nutrition: Feeding Tubes • Consider with weight loss, insufficient oral intake, dehydration or choking episodes • Potential benefits • Stabilize weight loss • Improve overall survival time • Possible improvement of quality of life • Access for medications • Can continue to eat as tolerated for pleasure without pressure of maintaining nutrition • Risks: complications from procedures, blockage, infection, does not eliminate risk of aspiration. Miller RG, Jackson CE, Kasarskis EJ et al. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009;73(15):1218

23. ALS and Nutrition: Feeding Tubes • Discuss early in disease course • Very personal decision • Consider timing of placement in context of respiratory status • Should be placed before vital capacity falls below 50% of predicted • Increased procedure risks with declining respiratory status • Review conditions under which patient might desire feeds to be withdrawn Miller RG, Jackson CE, Kasarskis EJ et al. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009;73(15):1218.

24. Respiratory Impairment • Progressive weakness of muscles of respiration • Hypoventilation • Best monitored by serial vital capacities • <50% predicted frequently associated with respiratory symptoms • <30% predicted risk of respiratory failure or death • Early signs • Daytime fatigue • Headache • Orthopnea • Nighttime dyspnea Rabinstein AA, Wijdicks EF. Warning signs of imminent respiratory failure in neurological patients. Semin Neurol. 2003;23(1):97

25. Respiratory Impairment: Noninvasive Positive Pressure Ventilation • Improved survival time • RTC 41 patients: Survival advantage of 205 days in ALS patients without severe bulbar dysfunction using noninvasive ventilation compared to standard care. • Improvement in quality of life • Improvement in symptom burden • Variety of masks available to increase tolerance • Less well tolerated in: • Dementia • Bulbar ALS Radunovic A, Annane D, Rafiqu MK, Mustfa N. Mechanical ventilation for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Sys Review.2013 Mar 28;(3):CD004427.

26. Respiratory Impairment: Management of Dyspnea • Assessment and treatment of additional underlying causes • pulmonary edema, pneumonia, bronchospasm • Opioids • Benzodiazepines • Concurrent management of secretions • Supplemental oxygen not recommended in absence of overt hypoxia

27. Respiratory Impairment:Mechanical Ventilation • Should be discussed early, on ongoing basis • Avoid decision making in emergent situations • Highly personal decision, views may change over time • Implemented in < 10% of patients • Should also discuss possible circumstances for withdrawal • Locked in status • Dementia

28. End-of-Life Care • Address patient and family concerns • Fear of choking or suffocation • Typically progressively decreased responsiveness due to hypercapnia • Reassurance regarding availability of symptom control measures and non-abandonment • Dyspnea • Secretions • Multiple routes available for administration of comfort medications • Referral to hospice and other supportive measures

29. ALS and Hospice • Critically impaired breathing capacity • Vital capacity <40% of normal • Dyspnea at rest, orthopnea, weakened cough or other signs of respiratory decline • Mechanical ventilation declined • Rapid progression of ALS and critical nutritional impairment evidenced by • Bedbound status • Barely or unintelligible speech • Dysphagia requiring purees • Progressive weight loss • Dependency in ADLs

30. ALS and the Military • Increased incidence of ALS with military service, independent of location, time of service, or branch of military • Considered a service connected diagnosis • Entitled to range of benefits if ALS developed during or following military service (at least 90 days of active duty) • regardless of branch, type of service, or location ALS in the Military: Unintended Consequences of Military Service. Feb 4, 2013. ASL Association.alsa.org/als-care/veterans/military-white-paper.html

31. Benefits for Veterans • Coverage of medications, medical care, and medical equipment • Disability compensation • Special Monthly Compensation • Specially adaptive housing grant • Automobile grant • Adaptive Equipment • Aid and Attendant allowance • Dependency and Indemnity compensation

32. ALS Resources • ALS association • Multidisciplinary clinics • Patient/caregiver resources • Equipment lending • Local organizations • Home based care • In person or online support communities • patientslikeme.com

33. Summary • ALS benefits from a multidisciplinary approach to care. • Goals of care should be addressed early and on an ongoing basis. • Despite the lack of cure, interventions exist that may prolong survival and improve quality of life.