Real Or Perceived Amyotrophic Lateral Sclerosis (ALS) Objectives

10/11/2019

Nursing Care and Considerations of Patients with Amyotrophic Lateral Sclerosis (ALS)

40th Annual Neurorehabilitation Conference on Traumatic Brain Injury, Stroke and Other Neurological Disorders Saturday & Sunday, November 16 & 17, 2019 Hyatt Regency Cambridge 575 Memorial Drive • Cambridge, MA encompasshealth.com/braintreerehab Vincent M. Vacca, Jr., MSN, RN

Conflicts of interest – Real or Perceived

• NONE

Amyotrophic Lateral Sclerosis (ALS) Objectives: 1. Following this presentation the learner will be able to list three signs and symptoms of motor neuron dysfunction found in ALS. 2. Following this presentation the learner will be able to explain three diagnostic tests utilized to establish diagnosis of ALS. 3. Following this presentation the learner will be able to describe three essential nursing interventions guided by best practices and care of patients with ALS.

1 10/11/2019

The median age of ALS onset is 55 years

• ALS affects about one in every 300 people. • About 30,000 currently with 5,000 new cases per year. • ALS is sporadic in 90% of cases and show familial inheritance in the remaining 10%. • Estimates of the median survival of people with ALS vary between 27 and 64 months. • Death from ALS is primarily pulmonary.

ALS is the most frequent motor neuron disorder in adults • Due to degeneration of upper and lower motor neurons in spinal and bulbar myotomes. • Most studies show male predominance with a gender ratio of 3:2, but gender differences are age related. • Age of onset tends to be later in females than in males (68.4 years vs. 61.5 years). • Limb-onset ALS is more frequent in males and bulbar onset predominates in females in all age groups.

There are multifactorial pathogenic processes underlying ALS • which are not yet fully determined. • Cellular events: • Oxidative stress, • Mitochondrial dysfunction, • Excitotoxicity (Glutamate), • Protein aggregation, • Impaired axonal transport, • Neuroinflammation, and • Dysregulated RNA signaling, • All can contribute to ALS.

2 10/11/2019

Upper & Lower Motor Neurons

• Clinical findings indicate where damage occurs: UMN v. LMN. • UMN disease/lesion/disorder results in increased muscle tone/reflexes. • Signs of UMN lesion: Weakness/Spasticity/Hyper-reflexia/ + Babinski/Clasp Knife. • LMN lesion results in decreased/absent muscle tone/reflexes. • Signs of LMN lesion: Weakness/Spasticity/Reduced tone & reflexes/fasiculations.

ALS – Lou Gehrig’s Disease

•Disease is motor not sensory. •May not see all the UMN & LMN signs but should see a mix of both.

3 10/11/2019

ALS is now universally recognized as a complex multisystem disorder • Approximately 15% of ALS patients have overt frontotemporal dementia (FTD), • and an additional 30–40% may have less severe cognitive impairment, that manifests largely as frontal lobe executive dysfunction.

Convincing evidence supports that ALS is a multisystem disease •not limited to motor areas alone but involving extra-motor areas as well and causing a variable degree of: •Cognitive, •Behavioral, •Dys-autonomic symptoms.

ALS symptoms usually begin in the distal limb or bulbar musculature, • and typically spread, causing progressive muscle weakness and eventually leading to death by respiratory insufficiency. • The median survival from symptom onset is 2–3 years, but there are great individual variations: (1) body region of onset (bulbar vs. spinal); (2) relative mix of UMN and LMN involvement; (3) progression rate; (4) age of onset, and (5) the presence of extra-motor symptoms.

4 10/11/2019

ALS • Will see ‘generalized’ weakness particularly - limb muscles. • The extra-ocular muscles/movements (EOMs) are preserved. • Many other cranial nerves affected leading to a ‘nasal speech’ pattern/swallowing impairment. (Bulbar)

Myelin sheath of nerves:

• Oligodendrocytes produce myelin. • Myelin facilitates signal transmission through the nerves at a rapid rate so we can respond to our environment in a split second. • In ALS oligodendrocytes degenerate and myelin is abnormal.

S&S – Bulbar & Limbs

• Voluntary muscle weakness, stiffness, twitching, cramps, spasticity, difficulty with posture, muscle atrophy, stiffness, slurred/nasal speech, dysphagia, chewing. • Usual onset is in arms/hands – will have difficulty writing or buttoning a shirt/tying a shoe for example. • If legs – awkward gait, stumbling, tripping. • Later stages: dyspnea & dysphagia. • Difficulties with Speaking/Swallowing & Breathing – eventual respiratory failure. • Poor prognosis and decreased survival time correlate with the nutritional status of patients with ALS. • If speech related symptoms appear first it’s called Bulbar onset ALS. • If limbs first – it’s Limb onset ALS.

5 10/11/2019

Weight loss and malnutrition are two common features of ALS • associated with a poor prognosis. • There is evidence suggesting that increased energy intake and a higher body mass index (BMI) of 30–35 may slow ALS progression and alter the clinical course of the disease. • Alter food consistency, integrate postural advice such as tucking the chin and flexing the neck when eating, consume oral nutrition supplements, and enteral or parenteral nutrition. • The value of EN likely exceeds that of maintaining BMI, studies have shown that EN can significantly decrease anxiety related to choking and, improve quality of life.

Review: Executive dysfunction is the most commonly cited cognitive impairment in ALS • Executive function encompasses several higher-order processes: • planning, • organization, • goal-directed activity, • working memory, • initiation, • behavioral regulation, and inhibitory control, • situation-appropriate decision-making on the basis of projected positive and negative outcomes in novel, complex or ambiguous situations. • Verbal fluency impairment has been consistently reported in ALS. • Language dysfunction is increasingly recognized as a core feature of ALS and has been consistently detected in patients without executive dysfunction. 17

Adherence to treatment - cognitive dysfunction;

• compliance with assistive devices, • participation in clinical trials, • making informed financial and end-of-life decisions, • choices in participating in non-licensed treatments are just some of the aspects of a patient journey which may be significantly affected by cognitive or behavioral deficits. • Cognitive impairment in ALS is widely regarded as a negative prognostic indicator and linked to reduced survival. • Neuropsychological deficits in ALS are thought to be associated with increased caregiver burden and reduced quality of life. • The recognition of the far-reaching effects of neuropsychological deficits on nearly all aspects of ALS care, caregiver support, resource allocation, and prognosis, led to the inclusion of specialist neuropsychologists as core members of ALS multidisciplinary teams worldwide. 18

6 10/11/2019

ALS survival • ~50% live up to 3 years after diagnosis. • ~10% live > 10 years after diagnosis. • Can affect anyone regardless of race/gender/ethnicity. • Does not affect senses of touch, smell, hearing, vision and taste. • No apparent risk factors – 90-95% occurs randomly. • 5-10% genetic. • Death is usually caused by respiratory failure - loss of motor neurons supplying innervation to the diaphragm and chest wall muscles. • The rate of decline of Forced Vital Capacity (FVC) predicts survival of patients with ALS.

ALS diagnosis

• Helpful to also ask a family member about some of the changes as the patient may not notice it as keenly as another. • Ex. Have your muscles shrunk or your voice changed. • Early diagnosis is challenging as the signs may be minimal. • The changes with ALS are consistent and progressive. • There are not ‘good’ days or ‘bad’ days.

ALS is a deadly disease – accurate diagnosis essential. • Electromyogram (EMG) is an accurate & confirmatory test for ALS done while patient is alive. • Patients/families need to understand the diagnosis. • End-of-life planning becomes essential.

7 10/11/2019

Early diagnosis offers the best prognosis for a longer, quality life while living with the disease. • Many medications are used to relieve symptoms but there are only 2 pharmacologic agents indicated for the management of ALS. • For 2 decades, riluzole had been the mainstay of disease-modifying therapy, but in 2017, edaravone became the second agent approved in the management of patients with ALS. • The mechanism of either agent is not well known. • Riluzole is thought to reduce damage to motor neurons through an inhibitory effect on glutamate release. • Edaravone is thought to act as a neuroprotective agent that prevents oxidative stress damage as a free radical scavenger.

• Muscle biopsy to investigate muscles in more detail. ALS Diagnosis • Electromyography (EMG) to measure electrical activity of muscles during contraction and relaxation. • No Specific test – like a biomarker. • Cortical thickness seems to be the • MRI – Can rule out herniated disc most promising neuroimaging (cervical), spinal cord tumors etc…w/ biomarker of ALS. similar symptoms. • Quantitative iron imaging is a very • Nerve conduction studies (NCS) – promising biomarker in ALS. measure ability of nerves to send impulses to muscles. • Diagnostic testing is done to exclude other neurologic • Genetic testing. conditions that have some • Electrical impedance myography - can similarity to ALS. measure changes in affected muscles – can also be used predict spread to other muscles.

Potential ALS mimickers include • cerebral lesions, • skull base tumors, • cervical spondylotic myelopathy, • stroke, and • thoraco/lumbo/sacral radiculopathy. • The revised criteria of the World Federation of Neurology Research Group on Motor Neuron Diseases recommend conventional imaging in “clinically probable” or “possible ALS”.

8 10/11/2019

ALS is terminal; has no cure and limited but important treatments • Riluzole – FDA approved 1995 – reduces glutamate in the synapse. • Extends survival by about 6 months. • This could be significant for the patient. • Diazepam – Spasticity • Gabapentin - Pain • Vitamin E can delay progression. • L-Dopa (PD) can increase dopamine concentrations. • Palliative care consult – grief, end of life planning. • Remember that patients with ALS are cognitively intact throughout.

Riluzole •Riluzole extended the median time to tracheostomy or death of patients with ALS by ~ 6 months in clinical trials. •Riluzole is recommended for all patients with ALS; however, there are few data to indicate if it is effective in patients who had onset more than 5 years prior.

Edaravone • is an antioxidant and free radical scavenger that was initially developed as an intravenous (IV) treatment of acute ischemic stroke. • It was approved by the FDA in May 2017. • Mechanism of action: antioxidant and free radical scavenger. • Efficacy: improves functional score, but long-term survival data are not fully evaluated. • Safety: relatively well tolerated; most common AEs are: gait disturbance, headache, dermatitis. • Other considerations: pharmacokinetics less variable than riluzole; high cost (>$145,000/year).

9 10/11/2019

Neither riluzole nor edaravone was shown to improve ALS symptomology:

• Cramps • Pain • Fatigue • Emotional lability • Spasticity • Communication • Pseudobulbar affect difficulties • Persistent saliva and • Constipation bronchial secretions • Depression • Excessive or violent • Insomnia yawning • Anxiety • Laryngospasm

Modafinil & NSAID’s

• Modafinil - demonstrated improved endurance in ALS with 1 study showing that 76% of patients with ALS responded to therapy versus 14% of patients who received a placebo. • NSAID’s - A typical characteristic of ALS is neuroinflammation. • Neuroinflammation is promoted by cyclooxygenase-2 (COX-2), and the activity of COX-2 can be inhibited by non-steroidal anti-inflammatory drugs (NSAIDs). • NSAIDs may have neuroprotective effects.

The Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) • is an instrument for evaluating the functional status of patients with ALS. • It can be used to monitor functional change in a patient over time. • Measures: (1) speech (2) salivation (3) swallowing (4) handwriting (5) cutting food and handling utensils (with or without gastrostomy) (6) dressing and hygiene (7) turning in bed and adjusting bed clothes (8) walking (9) climbing stairs (10) breathing

10 10/11/2019

Negative prognostic factors include:

• bulbar and respiratory site of disease onset, • executive dysfunction, & • decline in the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) prior to first evaluation.

Supportive care and treatments

• Nutritional support – early – easy to • Occupational Therapy – assist with chew and swallow but nutritionally preserving strength in hands/arms complete. and maintain independence as long as • Later stages – nutrition via enteral possible. feeding tube approach. • Speech Therapy – adaptive techniques • Physical Therapy – can assist with to improve speech and reducing pain and enhancing mobility. communication. • Low impact exercises for muscle • Psychological & Social Support for strength, mobility (ROM), patient/family – especially to prepare cardiovascular tone. for final stages of the disease. • Ventilatory support (NIV/PPV)– mechanical ventilation can prolong survival.

ALS = loss of motor neurons in the spinal cord, brainstem and motor cortex • Bulbar involvement leading to dysarthria and dysphagia is observed over the disease progression, but can be the region first affected in about one-third of ALS patients. • Severe dysphagia is a potential cause of malnutrition, which is a poor prognostic factor in ALS; as a result, nutritional assessment is a critical point of disease management. • Percutaneous endoscopic gastrostomy (PEG) is a standard procedure for feeding dysphagic amyotrophic lateral sclerosis (ALS) patients.

11 10/11/2019

Our study shows that in spite of PEG insertion, survival remains shorter in bulbar-onset patients • Probably, malnutrition is not the main reason for shorter survival in bulbar-onset patients. • As there is no evidence that respiratory function is more rapidly impaired in bulbar-onset than in spinal-onset patients, the poor outcome of bulbar patients should result from other problems, such as saliva aspiration or cough ineffectiveness.

• Survive a median time of eight months after PEG.Pena MJ, Ravasco P, Machado M, et al. What is the relevance of percutaneous endoscopic gastrostomy on the survival of patients with amyotrophic lateral sclerosis? Amyotrophic Lateral Sclerosis. 2012;13(6):550-554. doi:10.3109/17482968.2012.684215.

(ALS) is a progressive degenerative disease with respiratory insufficiency as its usual fatal consequence • Recently, the United States Food and Drug Administration (FDA) approved a Humanitarian Device Exemption (HDE) for a diaphragm pacing system for ALS patients. • A respiratory pacer simulates spontaneous breathing by delivering repetitive electrical stimuli to the phrenic nerve or its terminal branches, which contract the diaphragm and bring about inspiration. • Transmission of the pacer signals relies on an intact respiratory lower motor neuron (LMN) pathway including the phrenic motor neurons and their axons, the neuromuscular junction, and the diaphragm muscle. • Therefore, patients with respiratory insufficiency due to neurological conditions with upper motor neuron (UMN) lesions such as central hypoventilation, brainstem lesions, and spinal cord injuries can benefit from respiratory pacing.

Can phrenic pacing work in ALS?

• respiratory pacing cannot maintain the patency of the upper airway and may aggravate the airway collapse if pacing occurs out of synchrony with the spontaneous upper airway inspiratory dilation. • Concerns regarding the anesthesia, the procedure, device malfunction/failure. • Currently, non-invasive ventilation (NIV) is the standard care for management of respiratory failure in ALS. It increases the 18-month survival and significantly slows the decline in FVC (−3.5% change/month) compared to non-users (−8.3% change/month), and improves quality of life.

12 10/11/2019

Review: Prognosis – ALS is terminal/fatal disease with no known cure • Median survival is 3 years after • Patients with ALS and their appearance of symptoms. caregivers are at risk for • 20% live up to 5 years depression, feelings of • 10% live up to 10 years hopelessness, and anxiety as the • 5% live up to 20 years disease progresses. • Patients should try to maintain • Patients should prepare normalcy in their lives, for advanced directives for their instance, employment, social care, including respiration and activities, and standard and nutritional management, and preventive medical care (eg, end-of-life care. dental care, vaccinations).

ALS & Nursing Diagnoses • Impaired physical mobility – • Limitation of physical movement; related to progressive weakness. • Self-care deficit (ADL’s) related to weakness/cramps • Risk for self-feeding deficit; self-bathing deficit; self- dressing deficit; self-toileting deficit. • Risk for impaired skin integrity related to immobility, nutritional deficiency.

ALS & Nursing Diagnoses

• Potential for impaired respiratory function. • Decreased PO2/Increased PCO2, increased use of accessory muscles, decreased vital capacity, difficulty clearing airway secretions, daytime sleepiness. • Potential for impaired swallowing. • Sialorrhea, dysphagia, aspiration. • Risk for impaired communication. • Articulation deficit.

13 10/11/2019

ALS & Nursing Diagnoses • Pain. • Seen with immobility, contractures, subluxation, pressure. • Anxiety – related to progression of disease/impending death. • Emotional lability, worry about death impact, powerless, fear of dying process, caregiver/caregiver stress.

ALS Review

14 10/11/2019

ALS Review

Review: ALS is now universally recognized

• as a complex multisystem disorder with considerable extra-motor involvement. • The neuropsychological manifestations of frontotemporal, parietal, and basal ganglia involvement in ALS have important implications for • compliance with assistive devices, • survival, • participation in clinical trials, • caregiver burden, and the • management of individual care needs.

Future Directions/Clinical Trials - ALS • Stem Cell Therapies – can become any cell in the body and is useful for cell growth and repair. • Replenish cells where affected by ALS • Neural stem cells & Edaravone • Together are better than Riluzole, improved movement, reversed progression, extended lifespan.

15 10/11/2019

Future Directions/Clinical Trials - ALS

• Gene Therapies – deliver healthy copy of dysfunctional genes. • Bone marrow cells that secrete glial-cell derived neurotrophic factor (GDNF). • Normally GDNF keeps nerve cells healthy and alive. • Individual with ALS have lower levels of GDNF and nerve cell impairment. • NurOwn – study completed in 2018. • Safe, well tolerated and decreased rate of decline 6 months after injections. • Other clinical trials continue – even if not successful every clinical trial adds new knowledge for future trials.

469 completed/ongoing studies found for: ALS (Amyotrophic Lateral Sclerosis) • https://clinicaltrials.gov/ct2/home

Although rare, ALS is a devastating disease

• The National ALS Registry monitors ALS prevalence in the United States. • Registry data are important for trend analysis and the identification of possible risk factors.

16 10/11/2019

Motor neuron disease represents an important group of neurodegenerative disorders, • mainly represented by ALS. • Primary motor neuron involvement and degeneration and secondary mechanisms including glial cell pathological processes represent the most important features in the pathophysiology of ALS. • Astrocyte and microglial dysfunctions have been widely demonstrated in patients and animal models of ALS. • More studies are needed to establish specific molecular features linked to glial dysfunction at the microcellular level and its extracellular involvement, to allow new pharmacological perspectives and provide data about the natural history of the different genetic forms and variants of ALS. 49

Objectives #1 1. Signs and symptoms of ALS on 1. Following this upper and lower motor neurons presentation the includes: • Impaired gait due to muscle learner will be able weakness of voluntary limb to list three signs muscles. • Dysphagia associated with and symptoms of swallowing muscle weakness. • Dyspnea associated with lower motor weakness of respiratory muscles. neuron disease found in ALS. 50

2. Diagnostic testing in ALS is done to Objectives #2 exclude other neuro-muscular disorders leading to diagnosis of ALS. 2. Following this • Electromyography (EMG) to measure electrical activity of presentation the muscles during contraction and learner will be able to relaxation. • Nerve conduction studies (NCS) – explain three measure ability of nerves to send diagnostic tests impulses to muscles. • Electrical impedance myography - utilized to establish can measure changes in affected diagnosis of ALS. muscles – can also be used predict spread to other muscles.

17 10/11/2019

3. Both pharmacologic and non- pharmacologic interventions are Objectives #3 provided by nurses to provide best practices and care to patients with ALS. 3. Following this • Riluzole – FDA approved (1995) extends survival by about 6 months, presentation the which could be very significant for the learner will be able to patient. • Edaravone – FDA approved (2017) describe three improves functional score, but long- essential nursing term survival data are not fully evaluated. interventions guided • Nutritional support – early – easy to by best practices and chew and swallow but nutritionally complete. care of patients with • Palliative care consult – grief, end of ALS. life planning.

Resources for patients and families affected by ALS: • ALS Association www.alsa.org • ALS Therapy Development • Institute www.als.net • fALS Connect https://fals.patientcrossroads.org • Family Caregiver Alliance www.caregiver.org • Les Turner ALS Foundation www.lesturnerals.org • MDA (Muscular Dystrophy Association) www.mda.org • National Alliance for Caregiving www.caregiving.org • National Family Caregiver Action Network www.caregiveraction.org • Prize4Life www.prize4life.org • Project A.L.S. www.projectals.org • ALS ONE www.alsone.org/ • http://www.alsfindingacure.org/

ALS References • Andrews, J. A., Meng, L., Kulke, S. F., Rudnicki, S. A., Wolff, A. A., Bozik, M. E., Malik, F. I., … Shefner, J. M. (2017). Association Between Decline in Slow Vital Capacity and Respiratory Insufficiency, Use of Assisted Ventilation, Tracheostomy, or Death in Patients With Amyotrophic Lateral Sclerosis. JAMA neurology, 75(1), 58-64. • Schultz J. Disease-modifying treatment of amyotrophic lateral sclerosis. Am J Manag Care. 2018 Aug;24(15 Suppl):S327-S335. • Larson, T. C., Kaye, W., Mehta, P., & Horton, D. K. (2018). Amyotrophic Lateral Sclerosis Mortality in the United States, 2011-2014. Neuroepidemiology, 51(1-2), 96-103. • Mazón, M., Vázquez Costa, J. F., Ten-Esteve, A., & Martí-Bonmatí, L. (2018). Imaging Biomarkers for the Diagnosis and Prognosis of Neurodegenerative Diseases. The Example of Amyotrophic Lateral Sclerosis. Frontiers in neuroscience, 12, 784. doi:10.3389/fnins.2018.00784 • Jawaid, A., Khan, R., Polymenidou, M., & Schulz, P. E. (2018). Disease-modifying effects of metabolic perturbations in ALS/FTLD. Molecular neurodegeneration, 13(1), 63. doi:10.1186/s13024-018-0294-0 • Christidi, F., Karavasilis, E., Rentzos, M., Kelekis, N., Evdokimidis, I., & Bede, P. (2018). Clinical and Radiological Markers of Extra- Motor Deficits in Amyotrophic Lateral Sclerosis. Frontiers in neurology, 9, 1005. doi:10.3389/fneur.2018.01005 • Souza, Paulo Victor Sgobbi de, Pinto, Wladimir Bocca Vieira de Rezende, Rezende Filho, Flávio Moura, & Oliveira, Acary Souza Bulle. (2016). Far beyond the motor neuron: the role of glial cells in amyotrophic lateral sclerosis. Arquivos de Neuro-Psiquiatria, 74(10), 849-854. https://dx.doi.org/10.1590/0004-282X20160117 • Bader, M.K., Littlejohns, L.R. & Olson, D.M. (2016) AANN Core Curriculum for Neuroscience Nursing 6th Edition Chapter 23 Motor Neuron Diseases, pages 574-577. • Bellomo, T.L. & Cichminski, L. (2015) Amyotrophic lateral sclerosis: What nurses need to know. Nursing 2015; October Volume 45 Number 10, pages 45-51