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Prognosis and Multidisciplinary Care
ALS is a rare degenerative disorder of motor neurons of the cerebral cortex, brainstem, and spinal cord that results in progressive wasting and paralysis of voluntary muscles. The median age of onset is 55, and the disease has a slight male predominance. Fifty percent of patients with ALS die within three years of symptoms onset; 90% of patients die within five years. Patients with bulbar-onset ALS are more likely to die sooner. Riluzole is the only FDA-approved disease-modifying therapy for patients with ALS. Studies have indicated that this drug extends median survival by two to three months.
In addition, data suggest that multidisciplinary care improves quality of life and survival in patients with ALS. Traynor et al found that survival increased by 7.5 months among all patients in multidisciplinary clinics; patients with bulbar onset lived 9.5 months longer.
Managing Muscle Cramps
Recent studies suggest that muscle cramps occur in 85% of patients with ALS. Cramps can vary in severity and can be debilitating, said Dr. Weiss. Some patients can have as many as 50 cramps per day. Few efficacious treatments for managing this symptom of ALS are available. A recent trial showed that patients who received either 300 mg or 900 mg of mexiletine experienced significant declines in cramping.
Spasticity
It is common for patients with ALS to develop spasticity. Several therapies that may reduce spasticity include baclofen, tizanidine, diazepam, and botulinum toxin injections. The baclofen pump might be more helpful than these therapies for patients who have upper motor neuron dominance.
Sialorrhea
Sialorrhea occurs when patients are unable to clear extra saliva due to weakness in the oropharyngeal muscles. Doses of 600 mg to 1,200 mg of guaifenesin twice per day may be beneficial in managing sialorrhea. Other drying agents such as atropine drops and glycopyrrolate may also be efficacious. These drying agents may cause urinary retention in older patients, Dr. Weiss cautioned.
Amitriptyline can also help manage sialorrhea. It also improves sleep and reduces depression. Hyoscyamine, the transdermal scopolamine patch, and botulinum toxin injections into the submandibular glands may also be beneficial for patients. A suction machine or a mechanical in-exsufflator can also help manage this symptom of ALS.
Emotional Incontinence and Depression
Pseudobulbar affect, also known as emotional incontinence, affects as much as 50% of patients with ALS and is more common in bulbar ALS. This condition causes patients to have uncontrollable episodes of laughing and crying that are inconsistent with the patients’ mood. A randomized controlled trial found that dextromethorphan–quinidine was beneficial in managing these emotional symptoms. Other treatments include tricyclic antidepressants and selective serotonin reuptake inhibitors.
Reactive clinical depression occurs in 9% to 11% of patients with ALS. Once the ALS diagnosis is confirmed, patients should be counseled about their prognosis; their spouses and family members should also be offered counseling. Antidepressants such as tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors should be offered to all patients. These drugs may help to elevate mood, stimulate appetite, and improve sleep.
Respiratory Insufficiency and Falls
Respiratory insufficiency is one of the leading causes of death among patients with ALS. Patients with this condition may have morning headaches, vivid dreams and nightmares, frequent nocturnal arousals, fatigue, excessive daytime somnolence, and dyspnea on exertion. The American Academy of Neurology recommends that patients start noninvasive ventilation if their sniff nasal pressure is less than 40 cm, their maximal inspiratory pressure is less than –60 cm, or their forced vital capacity is less than 50%.
Bourke et al found that noninvasive ventilation was associated with improvement in quality of life and survival in patients with ALS. The median survival was increased by 205 days, and quality of life was maintained above 75% of baseline on the sleep apnea quality of life index score. In addition, patients who have a peak cough expiratory flow of less than 270 L/min should be offered a mechanical in-exsufflator suction device. If the patient does not tolerate noninvasive ventilation, then palliative medicine and hospice may be appropriate, said Dr. Weiss.
Evidence suggests that 2% of patients with ALS die from fall-related complications. Risk factors for falls in ALS include muscle weakness, deficits in gait or balance, and cognitive impairment. Assistive devices, wheelchairs, and physical therapy can help prevent falls. Some patients may need a brace to help stabilize their gait.
Managing Frontotemporal Dementia
Research suggests that 10% of patients with ALS develop frontotemporal dementia. Nearly 50% of these patients demonstrate behavioral changes such as apathy, disinhibition, and hostility. In addition, the incidence of frontotemporal dementia is higher in patients with familial ALS. The treatment of frontotemporal dementia remains symptomatic.
Observational studies have indicated that antidepressant medications, particularly serotonin reuptake inhibitors like sertraline, paroxetine, and trazadone, decrease disinhibition, anxiety, repetitive behaviors, and impulsivity. Although antipsychotic medications like quetiapine or olanzapine can limit agitation, they must be used cautiously, as they can cause extrapyramidal side effects. In addition, behavioral modification may also be helpful for problematic behavior. Finally, these patients
Dysphagia and Malnourishment
Between 16% and 55% of patients with ALS become malnourished because of dysphagia. This condition is characterized by difficulty with chewing and swallowing, nasal regurgitation, or coughing when drinking liquids. Nutritional status must be monitored every three months in patients with ALS, said Dr. Weiss. In addition, their BMI must be calculated and their weight measured. Paganoni et al found that the risk of death increased sevenfold in patients with ALS who had a BMI less than 18.5. Patients with ALS also need to be queried about the severity of choking, duration of meals, and caloric intake. A speech therapist should evaluate patients at every visit. Dietary changes might also be necessary and may include thickening liquids and preparing food that forms easily into a bolus.
As this disease progresses, patients may need a percutaneous gastrostomy (PEG) tube. According to the American Academy of Neurology practice guidelines, it is time to discuss PEG placement when a patient with ALS starts to lose weight. When a patient’s forced vital capacity is over 50%, the procedure can be done safely. When it is less than 50%, the procedure entails an increased risk of complications, including death.
Managing Dysarthria and Hospice
More than 95% of patients with ALS lose their ability to speak before they die. This condition, known as dysarthria, is difficult to treat. Almost all patients with bulbar-onset ALS and nearly 70% of patients with spinal-onset ALS develop dysarthria. Alternative augmentative communication devices and speech pathologists can be helpful. The Speakit application is a free speech-generating device available for the iPad, and a DynaVox device is a more costly augmentative and alternative communication tool. These devices help patients to communicate their needs and to stay connected to others.
As ALS advances, patients might require palliative medicine or hospice care. Before a patient reaches advanced stages of the disease, he or she should fill out a directive and Physician Orders for Life-Sustaining Treatment form, said Dr. Weiss. Patients must meet one of two criteria to receive Medicare reimbursement for hospice care. The first is a forced vital capacity of less than 30% with dyspnea at rest. The second is rapid progression of the disease with life-threatening complications (eg, infections) over 12 months or severe nutritional impairment over 12 months. Treatments for terminal dyspnea include morphine sulfate, oxygen, lorazepam, and chlorpromazine. These medications may depress respiratory drive, however, said Dr. Weiss.
Current Research and Recently Completed Trials
Smith et al found that dextromethorphan–quinidine may improve bulbar function. In addition, recent studies have found that diaphragmatic pacing, an FDA-approved technique, shortened the survival of patients with ALS by one year. An interanalysis found that patients using the diaphragmatic pacer died prematurely, compared with patients who had sham surgery in which electrodes were not implanted. Several phase II studies have suggested that tirasemtiv is substantially beneficial in decelerating slow vital capacity. Finally, a 24-week randomized controlled trial found that edaravone improved function in patients with definite or probable ALS. Edaravone was FDA-approved in May 2017.
—Erica Tricarico
Suggested Reading
Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev. 2012;(3):CD001447.
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):1218-1226.
Paganoni S, Deng J, Jaffa M, et al. Body mass index, not dyslipidemia, is an independent predictor of survival in amyotrophic lateral sclerosis. Muscle Nerve. 2011;44(1):20-24.
Shefner JM, Wolff AA, Meng L, et al. A randomized, placebo-controlled, double-blind phase IIb trial evaluating the safety and efficacy of tirasemtiv in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2016;17(5-6):426-435.
Smith R, Pioro E, Myers K, et al. Enhanced bulbar function in amyotrophic lateral sclerosis: The nuedexta treatment trial. Neurotherapeutics. 2017 Jan 9 [Epub ahead of print].
Traynor BJ, Alexander M, Corr B, et al. Effect of multidisciplinary amyotrophic lateral sclerosis (ALS) clinic on ALS survival: a population based study, 1996-2000. J Neurol Neurosurg Psychiatry. 2003;74(9):1258-1261.
Weiss MD, Macklin EA, Simmons Z, et al. A randomized trial of mexiletine in ALS: Safety and effects on muscle cramps and progression. Neurology. 2016;86(16):1474-1481.
Prognosis and Multidisciplinary Care
ALS is a rare degenerative disorder of motor neurons of the cerebral cortex, brainstem, and spinal cord that results in progressive wasting and paralysis of voluntary muscles. The median age of onset is 55, and the disease has a slight male predominance. Fifty percent of patients with ALS die within three years of symptoms onset; 90% of patients die within five years. Patients with bulbar-onset ALS are more likely to die sooner. Riluzole is the only FDA-approved disease-modifying therapy for patients with ALS. Studies have indicated that this drug extends median survival by two to three months.
In addition, data suggest that multidisciplinary care improves quality of life and survival in patients with ALS. Traynor et al found that survival increased by 7.5 months among all patients in multidisciplinary clinics; patients with bulbar onset lived 9.5 months longer.
Managing Muscle Cramps
Recent studies suggest that muscle cramps occur in 85% of patients with ALS. Cramps can vary in severity and can be debilitating, said Dr. Weiss. Some patients can have as many as 50 cramps per day. Few efficacious treatments for managing this symptom of ALS are available. A recent trial showed that patients who received either 300 mg or 900 mg of mexiletine experienced significant declines in cramping.
Spasticity
It is common for patients with ALS to develop spasticity. Several therapies that may reduce spasticity include baclofen, tizanidine, diazepam, and botulinum toxin injections. The baclofen pump might be more helpful than these therapies for patients who have upper motor neuron dominance.
Sialorrhea
Sialorrhea occurs when patients are unable to clear extra saliva due to weakness in the oropharyngeal muscles. Doses of 600 mg to 1,200 mg of guaifenesin twice per day may be beneficial in managing sialorrhea. Other drying agents such as atropine drops and glycopyrrolate may also be efficacious. These drying agents may cause urinary retention in older patients, Dr. Weiss cautioned.
Amitriptyline can also help manage sialorrhea. It also improves sleep and reduces depression. Hyoscyamine, the transdermal scopolamine patch, and botulinum toxin injections into the submandibular glands may also be beneficial for patients. A suction machine or a mechanical in-exsufflator can also help manage this symptom of ALS.
Emotional Incontinence and Depression
Pseudobulbar affect, also known as emotional incontinence, affects as much as 50% of patients with ALS and is more common in bulbar ALS. This condition causes patients to have uncontrollable episodes of laughing and crying that are inconsistent with the patients’ mood. A randomized controlled trial found that dextromethorphan–quinidine was beneficial in managing these emotional symptoms. Other treatments include tricyclic antidepressants and selective serotonin reuptake inhibitors.
Reactive clinical depression occurs in 9% to 11% of patients with ALS. Once the ALS diagnosis is confirmed, patients should be counseled about their prognosis; their spouses and family members should also be offered counseling. Antidepressants such as tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors should be offered to all patients. These drugs may help to elevate mood, stimulate appetite, and improve sleep.
Respiratory Insufficiency and Falls
Respiratory insufficiency is one of the leading causes of death among patients with ALS. Patients with this condition may have morning headaches, vivid dreams and nightmares, frequent nocturnal arousals, fatigue, excessive daytime somnolence, and dyspnea on exertion. The American Academy of Neurology recommends that patients start noninvasive ventilation if their sniff nasal pressure is less than 40 cm, their maximal inspiratory pressure is less than –60 cm, or their forced vital capacity is less than 50%.
Bourke et al found that noninvasive ventilation was associated with improvement in quality of life and survival in patients with ALS. The median survival was increased by 205 days, and quality of life was maintained above 75% of baseline on the sleep apnea quality of life index score. In addition, patients who have a peak cough expiratory flow of less than 270 L/min should be offered a mechanical in-exsufflator suction device. If the patient does not tolerate noninvasive ventilation, then palliative medicine and hospice may be appropriate, said Dr. Weiss.
Evidence suggests that 2% of patients with ALS die from fall-related complications. Risk factors for falls in ALS include muscle weakness, deficits in gait or balance, and cognitive impairment. Assistive devices, wheelchairs, and physical therapy can help prevent falls. Some patients may need a brace to help stabilize their gait.
Managing Frontotemporal Dementia
Research suggests that 10% of patients with ALS develop frontotemporal dementia. Nearly 50% of these patients demonstrate behavioral changes such as apathy, disinhibition, and hostility. In addition, the incidence of frontotemporal dementia is higher in patients with familial ALS. The treatment of frontotemporal dementia remains symptomatic.
Observational studies have indicated that antidepressant medications, particularly serotonin reuptake inhibitors like sertraline, paroxetine, and trazadone, decrease disinhibition, anxiety, repetitive behaviors, and impulsivity. Although antipsychotic medications like quetiapine or olanzapine can limit agitation, they must be used cautiously, as they can cause extrapyramidal side effects. In addition, behavioral modification may also be helpful for problematic behavior. Finally, these patients
Dysphagia and Malnourishment
Between 16% and 55% of patients with ALS become malnourished because of dysphagia. This condition is characterized by difficulty with chewing and swallowing, nasal regurgitation, or coughing when drinking liquids. Nutritional status must be monitored every three months in patients with ALS, said Dr. Weiss. In addition, their BMI must be calculated and their weight measured. Paganoni et al found that the risk of death increased sevenfold in patients with ALS who had a BMI less than 18.5. Patients with ALS also need to be queried about the severity of choking, duration of meals, and caloric intake. A speech therapist should evaluate patients at every visit. Dietary changes might also be necessary and may include thickening liquids and preparing food that forms easily into a bolus.
As this disease progresses, patients may need a percutaneous gastrostomy (PEG) tube. According to the American Academy of Neurology practice guidelines, it is time to discuss PEG placement when a patient with ALS starts to lose weight. When a patient’s forced vital capacity is over 50%, the procedure can be done safely. When it is less than 50%, the procedure entails an increased risk of complications, including death.
Managing Dysarthria and Hospice
More than 95% of patients with ALS lose their ability to speak before they die. This condition, known as dysarthria, is difficult to treat. Almost all patients with bulbar-onset ALS and nearly 70% of patients with spinal-onset ALS develop dysarthria. Alternative augmentative communication devices and speech pathologists can be helpful. The Speakit application is a free speech-generating device available for the iPad, and a DynaVox device is a more costly augmentative and alternative communication tool. These devices help patients to communicate their needs and to stay connected to others.
As ALS advances, patients might require palliative medicine or hospice care. Before a patient reaches advanced stages of the disease, he or she should fill out a directive and Physician Orders for Life-Sustaining Treatment form, said Dr. Weiss. Patients must meet one of two criteria to receive Medicare reimbursement for hospice care. The first is a forced vital capacity of less than 30% with dyspnea at rest. The second is rapid progression of the disease with life-threatening complications (eg, infections) over 12 months or severe nutritional impairment over 12 months. Treatments for terminal dyspnea include morphine sulfate, oxygen, lorazepam, and chlorpromazine. These medications may depress respiratory drive, however, said Dr. Weiss.
Current Research and Recently Completed Trials
Smith et al found that dextromethorphan–quinidine may improve bulbar function. In addition, recent studies have found that diaphragmatic pacing, an FDA-approved technique, shortened the survival of patients with ALS by one year. An interanalysis found that patients using the diaphragmatic pacer died prematurely, compared with patients who had sham surgery in which electrodes were not implanted. Several phase II studies have suggested that tirasemtiv is substantially beneficial in decelerating slow vital capacity. Finally, a 24-week randomized controlled trial found that edaravone improved function in patients with definite or probable ALS. Edaravone was FDA-approved in May 2017.
—Erica Tricarico
Suggested Reading
Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev. 2012;(3):CD001447.
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):1218-1226.
Paganoni S, Deng J, Jaffa M, et al. Body mass index, not dyslipidemia, is an independent predictor of survival in amyotrophic lateral sclerosis. Muscle Nerve. 2011;44(1):20-24.
Shefner JM, Wolff AA, Meng L, et al. A randomized, placebo-controlled, double-blind phase IIb trial evaluating the safety and efficacy of tirasemtiv in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2016;17(5-6):426-435.
Smith R, Pioro E, Myers K, et al. Enhanced bulbar function in amyotrophic lateral sclerosis: The nuedexta treatment trial. Neurotherapeutics. 2017 Jan 9 [Epub ahead of print].
Traynor BJ, Alexander M, Corr B, et al. Effect of multidisciplinary amyotrophic lateral sclerosis (ALS) clinic on ALS survival: a population based study, 1996-2000. J Neurol Neurosurg Psychiatry. 2003;74(9):1258-1261.
Weiss MD, Macklin EA, Simmons Z, et al. A randomized trial of mexiletine in ALS: Safety and effects on muscle cramps and progression. Neurology. 2016;86(16):1474-1481.
Prognosis and Multidisciplinary Care
ALS is a rare degenerative disorder of motor neurons of the cerebral cortex, brainstem, and spinal cord that results in progressive wasting and paralysis of voluntary muscles. The median age of onset is 55, and the disease has a slight male predominance. Fifty percent of patients with ALS die within three years of symptoms onset; 90% of patients die within five years. Patients with bulbar-onset ALS are more likely to die sooner. Riluzole is the only FDA-approved disease-modifying therapy for patients with ALS. Studies have indicated that this drug extends median survival by two to three months.
In addition, data suggest that multidisciplinary care improves quality of life and survival in patients with ALS. Traynor et al found that survival increased by 7.5 months among all patients in multidisciplinary clinics; patients with bulbar onset lived 9.5 months longer.
Managing Muscle Cramps
Recent studies suggest that muscle cramps occur in 85% of patients with ALS. Cramps can vary in severity and can be debilitating, said Dr. Weiss. Some patients can have as many as 50 cramps per day. Few efficacious treatments for managing this symptom of ALS are available. A recent trial showed that patients who received either 300 mg or 900 mg of mexiletine experienced significant declines in cramping.
Spasticity
It is common for patients with ALS to develop spasticity. Several therapies that may reduce spasticity include baclofen, tizanidine, diazepam, and botulinum toxin injections. The baclofen pump might be more helpful than these therapies for patients who have upper motor neuron dominance.
Sialorrhea
Sialorrhea occurs when patients are unable to clear extra saliva due to weakness in the oropharyngeal muscles. Doses of 600 mg to 1,200 mg of guaifenesin twice per day may be beneficial in managing sialorrhea. Other drying agents such as atropine drops and glycopyrrolate may also be efficacious. These drying agents may cause urinary retention in older patients, Dr. Weiss cautioned.
Amitriptyline can also help manage sialorrhea. It also improves sleep and reduces depression. Hyoscyamine, the transdermal scopolamine patch, and botulinum toxin injections into the submandibular glands may also be beneficial for patients. A suction machine or a mechanical in-exsufflator can also help manage this symptom of ALS.
Emotional Incontinence and Depression
Pseudobulbar affect, also known as emotional incontinence, affects as much as 50% of patients with ALS and is more common in bulbar ALS. This condition causes patients to have uncontrollable episodes of laughing and crying that are inconsistent with the patients’ mood. A randomized controlled trial found that dextromethorphan–quinidine was beneficial in managing these emotional symptoms. Other treatments include tricyclic antidepressants and selective serotonin reuptake inhibitors.
Reactive clinical depression occurs in 9% to 11% of patients with ALS. Once the ALS diagnosis is confirmed, patients should be counseled about their prognosis; their spouses and family members should also be offered counseling. Antidepressants such as tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors should be offered to all patients. These drugs may help to elevate mood, stimulate appetite, and improve sleep.
Respiratory Insufficiency and Falls
Respiratory insufficiency is one of the leading causes of death among patients with ALS. Patients with this condition may have morning headaches, vivid dreams and nightmares, frequent nocturnal arousals, fatigue, excessive daytime somnolence, and dyspnea on exertion. The American Academy of Neurology recommends that patients start noninvasive ventilation if their sniff nasal pressure is less than 40 cm, their maximal inspiratory pressure is less than –60 cm, or their forced vital capacity is less than 50%.
Bourke et al found that noninvasive ventilation was associated with improvement in quality of life and survival in patients with ALS. The median survival was increased by 205 days, and quality of life was maintained above 75% of baseline on the sleep apnea quality of life index score. In addition, patients who have a peak cough expiratory flow of less than 270 L/min should be offered a mechanical in-exsufflator suction device. If the patient does not tolerate noninvasive ventilation, then palliative medicine and hospice may be appropriate, said Dr. Weiss.
Evidence suggests that 2% of patients with ALS die from fall-related complications. Risk factors for falls in ALS include muscle weakness, deficits in gait or balance, and cognitive impairment. Assistive devices, wheelchairs, and physical therapy can help prevent falls. Some patients may need a brace to help stabilize their gait.
Managing Frontotemporal Dementia
Research suggests that 10% of patients with ALS develop frontotemporal dementia. Nearly 50% of these patients demonstrate behavioral changes such as apathy, disinhibition, and hostility. In addition, the incidence of frontotemporal dementia is higher in patients with familial ALS. The treatment of frontotemporal dementia remains symptomatic.
Observational studies have indicated that antidepressant medications, particularly serotonin reuptake inhibitors like sertraline, paroxetine, and trazadone, decrease disinhibition, anxiety, repetitive behaviors, and impulsivity. Although antipsychotic medications like quetiapine or olanzapine can limit agitation, they must be used cautiously, as they can cause extrapyramidal side effects. In addition, behavioral modification may also be helpful for problematic behavior. Finally, these patients
Dysphagia and Malnourishment
Between 16% and 55% of patients with ALS become malnourished because of dysphagia. This condition is characterized by difficulty with chewing and swallowing, nasal regurgitation, or coughing when drinking liquids. Nutritional status must be monitored every three months in patients with ALS, said Dr. Weiss. In addition, their BMI must be calculated and their weight measured. Paganoni et al found that the risk of death increased sevenfold in patients with ALS who had a BMI less than 18.5. Patients with ALS also need to be queried about the severity of choking, duration of meals, and caloric intake. A speech therapist should evaluate patients at every visit. Dietary changes might also be necessary and may include thickening liquids and preparing food that forms easily into a bolus.
As this disease progresses, patients may need a percutaneous gastrostomy (PEG) tube. According to the American Academy of Neurology practice guidelines, it is time to discuss PEG placement when a patient with ALS starts to lose weight. When a patient’s forced vital capacity is over 50%, the procedure can be done safely. When it is less than 50%, the procedure entails an increased risk of complications, including death.
Managing Dysarthria and Hospice
More than 95% of patients with ALS lose their ability to speak before they die. This condition, known as dysarthria, is difficult to treat. Almost all patients with bulbar-onset ALS and nearly 70% of patients with spinal-onset ALS develop dysarthria. Alternative augmentative communication devices and speech pathologists can be helpful. The Speakit application is a free speech-generating device available for the iPad, and a DynaVox device is a more costly augmentative and alternative communication tool. These devices help patients to communicate their needs and to stay connected to others.
As ALS advances, patients might require palliative medicine or hospice care. Before a patient reaches advanced stages of the disease, he or she should fill out a directive and Physician Orders for Life-Sustaining Treatment form, said Dr. Weiss. Patients must meet one of two criteria to receive Medicare reimbursement for hospice care. The first is a forced vital capacity of less than 30% with dyspnea at rest. The second is rapid progression of the disease with life-threatening complications (eg, infections) over 12 months or severe nutritional impairment over 12 months. Treatments for terminal dyspnea include morphine sulfate, oxygen, lorazepam, and chlorpromazine. These medications may depress respiratory drive, however, said Dr. Weiss.
Current Research and Recently Completed Trials
Smith et al found that dextromethorphan–quinidine may improve bulbar function. In addition, recent studies have found that diaphragmatic pacing, an FDA-approved technique, shortened the survival of patients with ALS by one year. An interanalysis found that patients using the diaphragmatic pacer died prematurely, compared with patients who had sham surgery in which electrodes were not implanted. Several phase II studies have suggested that tirasemtiv is substantially beneficial in decelerating slow vital capacity. Finally, a 24-week randomized controlled trial found that edaravone improved function in patients with definite or probable ALS. Edaravone was FDA-approved in May 2017.
—Erica Tricarico
Suggested Reading
Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev. 2012;(3):CD001447.
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):1218-1226.
Paganoni S, Deng J, Jaffa M, et al. Body mass index, not dyslipidemia, is an independent predictor of survival in amyotrophic lateral sclerosis. Muscle Nerve. 2011;44(1):20-24.
Shefner JM, Wolff AA, Meng L, et al. A randomized, placebo-controlled, double-blind phase IIb trial evaluating the safety and efficacy of tirasemtiv in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2016;17(5-6):426-435.
Smith R, Pioro E, Myers K, et al. Enhanced bulbar function in amyotrophic lateral sclerosis: The nuedexta treatment trial. Neurotherapeutics. 2017 Jan 9 [Epub ahead of print].
Traynor BJ, Alexander M, Corr B, et al. Effect of multidisciplinary amyotrophic lateral sclerosis (ALS) clinic on ALS survival: a population based study, 1996-2000. J Neurol Neurosurg Psychiatry. 2003;74(9):1258-1261.
Weiss MD, Macklin EA, Simmons Z, et al. A randomized trial of mexiletine in ALS: Safety and effects on muscle cramps and progression. Neurology. 2016;86(16):1474-1481.