Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, was first described in the 19th century by French neurologist Dr. Jean-Martin Charcot. In the 20th century, ALS also became known as Lou Gehrig disease, named after the famous New York Yankees baseball player who had the disease. Lou Gehrig died from ALS in 1941 at the age of 37.1
ALS is the most common form of motor neuron disease and is the third-most common neurodegenerative disorder behind Alzheimer and Parkinson diseases.2 There are an estimated 300,000 individuals currently living with ALS in the US.3 The median age of onset is 55 and the disease incidence peaks between 70 and 75 years of age.1,4 Males are affected more than females. About 90% of ALS cases are determined to be sporadic, or acquired, while the remainder are considered familial or hereditary. Known risk factors include age and family history, but there is now evidence that cigarette smoking is also a risk factor for ALS.1
This article provides critical care nurses with information about the etiology and pathophysiology, signs and symptoms, and diagnosis of ALS, as well as nursing considerations to help patients at end of life. Although treatment can slow disease progression, it is important for critical care nurses to understand that treatment is not curative.
Etiology and pathophysiology
Although the underlying cause of ALS is not completely understood, a variety of damaging cellular events have been identified as suspected contributors to the pathology of ALS. These include:1,4
- oxidative stress
- mitochondrial dysfunction
- protein aggregation
- impaired axonal transport
- dysregulated RNA signaling.
The excitotoxicity hypothesis suggests that glutamate, which is a naturally occurring neurotransmitter may initiate a cascade that results in cell death of motor neurons. It is thought that excessive activation of glutamate receptors leads to increased intracellular calcium, which then triggers neuronal cell death.
Dysfunction and then failure of upper motor neurons (UMNs) in the brain, brainstem, and spinal cord—also known as the corticospinal tract—leads to lower motor neuron involvement causing atrophy or wasting of the corresponding muscle fibers. Muscle atrophy is the basis for the term amyotrophic in ALS.3,5
As UMNs become progressively dysfunctional early in the disease, a gradually developing asymmetric weakness usually becomes evident distally in one of the lower extremities. For example, individuals at this stage of the disease may experience lower motor neuron effects, including a unilateral foot drop or weakened lower extremity. Patients may also report painful muscle cramping with volitional movements, typically in the early hours of the morning, for example, while stretching in bed before arising. Disease progression is associated with muscle twitching or fasciculation. Another feature associated with UMN dysfunction is hyperactivity of the muscle-stretch reflexes, for example the knee-jerk reflex. Due to reflexive hyperactivity, individuals at this stage of the disease will experience muscle stiffness more than muscle weakness.3,5
If the initial presentation of ALS involves bulbar rather than limb muscles, the disease signs and symptoms are manifested by difficulty with chewing, swallowing, and movements of the face and tongue. There may also be exaggeration of the motor expressions of emotion, and involuntary excesses in weeping or laughing, which is called pseudobulbar affect.3,5
In ALS, any muscle or muscle group may be the first to show signs of disease, resulting in a unilateral or asymmetric impairment. As time passes, more and more muscles become involved until the disease takes on a symmetric distribution in all regions, including the muscles of respiration.3,5
UMN signs include hyperreflexia, spastic gait, and clonus or rhythmic muscular contractions and relaxations. Clonus is often accompanied by spasticity of affected muscles. Lower motor neuron (LMN) signs and symptoms include muscle atrophy, weakness, and flaccidity. It is characteristic of ALS that both UMNs and LMNs will eventually be affected. However, sensory, bowel, bladder, and cognitive functions are preserved throughout the disease. Ocular motility is also typically preserved until the very late stages of the disease.3,5 (See UMN and LMN signs and symptoms of ALS.)
Relevant anatomy and physiology
The motor cortex of the brain processes incoming signals, plans, and creates the electrical impulses that quickly lead to voluntary muscle movements. The myelinated nerve fibers that descend from the motor cortex to the brainstem and spinal cord are called the UMNs, and the nerves exiting from the spinal cord that connect to skeletal muscles are the LMNs.7,8 (See Motor neuron changes in ALS.) Myelin is a fatty substance that is produced in both the central and peripheral nervous systems. Myelin forms a sheath that wraps around nerve axons and provides vital supporting functions as well as increases the rate of nerve conduction to target muscles and organs. The myelin sheath acts as an insulator that protects the integrity and facilitates the speed and intensity of the nerve impulse that reaches the target muscle or muscle group. Disruptions of the myelin sheath occur in ALS and contribute to the muscle dysfunction seen in ALS.3,9
Beginning at the motor cortex of the brain, the UMNs descend through the brain and decussate or cross over in the medulla to form the lateral corticospinal tract. The lateral corticospinal tract contains over 90% of nerve fibers present in the corticospinal tract and runs the entire length of the spinal cord. (See The corticospinal tract.) The lateral corticospinal tract is primarily responsible for voluntary movement of the contralateral limbs. The UMN then synapses with an LMN in the anterior horn of the spinal cord at the appropriate level. The LMN then exits the spinal cord to synapse to a skeletal muscle. In ALS the dysfunction occurs at the UMN, in the lateral corticospinal tract, leading to a slower and weaker nerve impulse arriving at the synapse to the LMN. The slower and weaker nerve impulse arriving at the LMN leads to the motor signs seen in ALS, which are a combination of hyperreflexia, spasticity and weakness of the specific muscles or muscle groups.7,8
Signs and symptoms
Signs and symptoms of ALS depend on which somatosensory motor cortex area and corresponding UMN nerve fibers are affected. Approximately 70% of individuals present with upper or lower limb-onset ALS, about 25% have bulbar-onset disease, and the remaining 5% have truncal muscle onset, which can include respiratory muscle involvement. Bulbar involvement is an LMN manifestation of ALS and is associated with weakness in both palatal and tongue muscles and movement. Dysphagia, or difficulty swallowing, and dysarthria, or slurring of speech, are seen with bulbar involvement. Cervical level onset ALS, which can affect UMNs and or LMNs, is associated with upper-limb signs of weakness or spasticity and can be either unilateral or bilateral. For example, weakness of upper limbs presents problems affecting daily activities such as hair washing and combing, teeth brushing, and difficulties with precise movements such as catching, pinching, grasping, and manipulating small objects. Lumbar-onset ALS is associated with signs and symptoms that can include muscle fasciculation, muscle wasting, and weakness of the lower extremities.5,8
UMN signs can be further divided into negative and positive signs. Negative signs and symptoms involve loss of motor control, and include weakness, loss of dexterity, fatigue, and impaired motor planning and control. Positive signs and symptoms are increased and spastic muscle activity and exaggerated spinal reflexes. Positive signs include hyperreflexia, clonus or involuntary, rhythmic, muscular contractions and relaxations, spasticity, and spasms. LMN signs typically present with muscle atrophy, paralysis of individual muscles, fasciculation, hypotonia, and hyporeflexia.6
As ALS progresses, it eventually causes such severe dysphagia and dyspnea that the individual is unable to speak above a whisper, swallow or breathe effectively, and generally dies from respiratory failure. Death from ALS typically occurs 3 to 5 years following disease onset.10
Currently there is no specific biomarker used to diagnose ALS. The diagnosis of ALS remains clinical, based on the detection of UMN signs, LMN signs, and the exclusion of ALS mimics. Within the disease class known as motor neuron diseases, ALS makes up approximately 70% of the total number of cases. Other motor neuron diseases that mimic ALS include; isolated bulbar palsy, progressive muscular atrophy and primary lateral sclerosis.11 ALS pathology involves a mix of both UMN and LMN signs.4 In addition to clinical evaluation, a diagnosis is made with nerve conduction studies and electromyography. Nerve conduction studies measure the ability of nerves to send impulses to muscles and electromyography measures presence and strength of electrical activity during muscle contraction and relaxation. Another study called electrical impedance myography measures stimulation changes in muscles and can be used to predict the spread of disease to other muscles. Imaging of the brain and spinal cord, including computed tomography, MRI, and serum lab studies, are used to rule out differential diagnoses that also manifest with muscle weakness, but are not ALS.4,6
A committee of the World Federation of Neurology has established diagnostic guidelines for ALS.4 Essential for the diagnosis is simultaneous upper and lower motor neuron involvement with progressive weakness and the exclusion of alternative diagnoses. According to World Federation guidelines, ALS diagnosis is considered definite when three or four of the following sites of UMNs and/or LMNs are involved:
When only two sites are involved, the diagnosis is probable, and when only one site is implicated, the diagnosis is possible.1 (See The four regions of the body.)
The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is an instrument for evaluating the functional status of patients with ALS. The scale has a minimum of 0 points and a maximum of 48 points. It can be used to monitor functional change in a patient over time. Each category has several point-associated conditions with lower points resulting from increased impairment. The scale shows close agreement with objective measurements of muscle strength and pulmonary function. It also is sensitive to changes in the patient condition resulting from disease progression and is both reliable and consistent as a testing and retesting tool.12
The ALSFRS-R score is calculated using a patient survey that assesses activities of daily living and respiratory function. It is currently considered the primary metric for assessing overall ALS disease progression. Decline in ALSFRS-R score signifies disease progression.12 (See ALS resources.)
Two drugs approved by the FDA are considered disease-modifying treatments for ALS—riluzole and edaravone. Although the precise mechanism of action for either drug is unknown, riluzole is thought to reduce damage to motor neurons through an inhibitory effect on the excitatory neurotransmitter glutamate release. Riluzole extended the median time to tracheostomy or death of patients with ALS by 2 to 3 months in clinical trials. Edaravone is thought to act as a neuroprotective agent that prevents oxidative stress damage to nerve cells as a free radical scavenger. Edaravone is an antioxidant and free radical scavenger that was initially developed as an I.V. treatment of acute ischemic stroke. It was approved by the FDA in May 2017 for use in ALS. Although edaravone is an option that may offer some benefit to individuals with ALS, it is not curative and there are significant drug-related concerns that must be addressed. First, edaravone is only available as an I.V. medication. Second is the high cost with estimates of approximately $145,000/year.13
Supportive pharmacologic therapies can include muscle relaxants for muscle cramps, which are commonly experienced by individuals with ALS. Fatigue is another common component of ALS. The drug modafinil has demonstrated improved endurance in ALS with one study showing that 76% of patients with ALS responded favorably to this therapy. Muscle fasciulations and spasticity which typically occur early in the disease process due to muscle wasting or atrophy may be managed with drugs such as baclofen or tizanidine. Many individuals with ALS experience excessive drooling, or sialorrhea. Anticholinergic drugs can be beneficial to manage sialorrhea. Individuals with ALS may experience involuntary and excessive emotional manifestations such as laughing or crying due to a pseudobulbar effect associated with ALS. Antidepressants or other mood-altering drugs may be beneficial to these patients.3,13
Although no curative pharmacologic therapy exists for ALS, a variety of rehabilitative aids may substantially assist ALS patients. Foot-drop splints facilitate ambulation by preventing tripping. Finger extension splints can potentiate gripping ability. Respiratory support by artificial airway and mechanical ventilation may be life-sustaining. For some individuals noninvasive positive pressure ventilation provides transient relief (weeks to months) from respiratory insufficiency and can prevent or manage hypercarbia and hypoxemia. Also extremely beneficial for airway protection and maintenance is cough augmentation with a mechanical insufflation-exsufflation device. This is highly effective in clearing airways and preventing aspiration pneumonia. When bulbar disease prevents normal chewing and swallowing, a gastrostomy tube is helpful by providing a route for restoring normal nutrition and hydration. Currently, a variety of speech synthesizers are available to augment speech, especially when there is advanced bulbar involvement. These devices facilitate oral communication.3
End of life
On average, an individual with ALS can live up to 5 years after symptom onset. Shortly after onset, patients, families, and caregivers should discuss advanced planning and begin to make decisions regarding end-of-life care. Patients with ALS often retain the mental capacity to make decisions about end-of-life care even when close to death. ALS can impair the patient's communication abilities, so it is essential to plan for end-of-life care before communication skills deteriorate. Individuals should be offered the option to create a living will and/or advance directives to detail their end-of-life preferences and plans while still in an early stage of ALS.14
Patients should consider if they wish to prolong their life with mechanical ventilation by an artificial airway, such as a tracheostomy, or if they would be unhappy with this quality of life.14
Individuals with ALS may also struggle emotionally with facing death from the disease and require emotional support from their family, friends, and caregivers. Critical care nurses and other healthcare professionals should anticipate these needs. Promote patient-centered care by enhancing communication between the patient, their family, and care providers.14
Patients with ALS are unique individuals with a variety of perspectives on end-of-life care. Critical care nurses are well situated to provide a holistic end-of-life care approach to patients with ALS.14
Encourage patients to remain involved in decision-making regarding pursuit or rejection of life-sustaining support. These individuals may need assistance coping with and processing their fears of the future. The coping process during any degenerative disease can vary among patients. Discovering and trying to understand how individuals cope with the situation allows healthcare providers as well as those affected to develop a collaborative and acceptable plan for the end-of-life phase. Keeping communication channels open between clinicians, the patient, and family is critical to delivering optimal patient care at the end-of-life phase of ALS.14
Because the presentation and progression of ALS can vary between patients, critical care nurses should discuss comprehensive aspects of ALS with patients to learn how each wants treatment to proceed.14
Patients may resent relinquishing control of various facets of their lives to their families or caregivers. Timing is vital when planning discussions about life-sustaining measures. Clinicians should remain alert to all aspects of each patient's ALS journey. For example, some patients prefer to die at home in the presence of family than in a healthcare facility. Healthcare providers should explore and facilitate this option and help coordinate it when possible. Each patient experience is unique, so allowing patients into the decision-making process as early as possible can give them a sense of control over their end-of-life process.14
All healthcare providers need to understand and be aware of the patients' wishes throughout their entire journey of ALS care. Healthcare providers must communicate to the patient in such a way that the patient and/or family or caregivers do not feel pressured to make life-sustaining decisions that may not be acceptable to them. A consultation with palliative care specialists could improve communication and interactions for the patient with ALS.14
Because most individuals with ALS have lived independently before their diagnosis, some may resist accepting advice or assistance from healthcare providers. The reality of their physical deterioration means they cannot continue living as they used to. This is a significant emotional hurdle that healthcare providers must recognize and respond to in a sensitive and patient-centered manner. Holistic care provided by nurses can assist and generate satisfaction and an overall sense of peace in daily functioning for these individuals and their families. The challenges associated with losing their independence can be exacerbated if patients and families perceive that healthcare providers are not providing clear information in a sensitive and respectful manner. By providing a holistic approach to care with empathy for the patient's experience can provide comfort during disease progression and especially during the end-of-life phase.14
Patients' decisions about their own life-sustaining support are essential and should include full disclosure by healthcare providers, so that every individual with ALS can make the best decisions for them.14
Comprehensive nursing care along with holistic elements (focusing on mind, body, spirit, and emotional well-being) can help critical care nurses positively impact patients with ALS at the end of life.14
There are currently over 600 clinical trials worldwide studying all aspects of ALS.15
In the US, the CDC and other collaborators maintain a national ALS registry. The purpose of this national ALS registry is to:
- better describe the incidence and prevalence of ALS in the US.
- examine appropriate factors, both environmental and occupational, that may be associated with the disease.
- better outline key demographic factors (such as age, race or ethnicity, gender, and family history of individuals who are diagnosed with the disease) associated with the disease.
- better examine the connection between ALS and other motor neuron disorders that can be confused with ALS, misdiagnosed as ALS, and in some cases progress to ALS.15
ALS is a relentless and progressive disease process without remissions or exacerbations. The rate of progression of ALS varies between affected individuals but the symptoms, which typically appear in a unilateral or asymmetric limb, will spread in a predictable manner eventually causing life-threatening neuromuscular respiratory failure. Nurses are in a key position to provide holistic care and support to patients and families throughout their ALS journey.
- ALS Association www.alsa.org
- ALS Therapy Development Institute www.als.net
- ALSFRS-R tool https://n.neurology.org/content/suppl/2006/10/07/67.7.1294.DC1/E3.pdf
- 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
- Project A.L.S. www.projectals.org
- ALS ONE www.alsone.org
- ALS Finding a Cure www.alsfindingacure.org.
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