What Special Considerations Are Needed for Individuals with Amyotrophic Lateral Sclerosis, Parkinson’s Disease, and Multiple Sclerosis?

Introduction and Scope of the Problem

Neurodegenerative diseases affect adults of all ages and are associated with complex physical and neuropsychiatric symptoms, progressive functional impairments, and high levels of personal and caregiver suffering. Although amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Parkinson’s disease (PD) are distinct disease entities varying in prevalence and disease trajectories, they share numerous characteristics and care needs. All are associated with multiple domains of loss and profound disruptions of patient roles and relationships. Despite significant neurological advancements in the understanding and treatment of these diseases in recent decades, they all remain incurable and are associated with significant symptom burden.

Palliative care services are underutilized in MS and PD compared to ALS, due in large part to differences in disease trajectories. Whereas ALS is a relentlessly progressive and sometimes rapidly fatal condition, MS and PD are chronic conditions that generally progress slowly over a period of many years. Other barriers to palliative care include prognostic uncertainty and lack of recognition by health providers, patients, and families about the meaning and benefits of palliative care. Core palliative care tasks include communication and setting expectations with patients and families, management of symptoms, psychosocial support, and coordination of medical and social services. These tasks may take place over a short time for a rapidly progressive case of ALS or over many years for MS or PD. There is an increasing recognition of the role that palliative care teams play in supporting patients with neurodegenerative disease and their loved ones throughout the disease course.

Patients with neurodegenerative diseases require a comprehensive multispecialty approach and care coordination. Patients commonly have difficulties accessing coordinated care. Multidisciplinary care models are most widely accepted as the evidence-based standard of care for ALS and are associated with quality of life and survival benefits. More than 180 multidisciplinary ALS clinics operate in the United States (U.S.) certified by voluntary disease organizations, including the ALS Association and Muscular Dystrophy Association (MDA). Although interdisciplinary clinics for MS and PD care are also becoming more common and increasingly recognized as optimal care models, many patients lack access to this type of coordinated care team. Furthermore, these disease-specific clinics rarely formally incorporate palliative care specialists, although it is becoming more common.

Epidemiology and Disease Trajectory

Neurodegenerative diseases vary greatly in their prevalence, risk factors, typical onset age, and disease trajectories. Recognizing disease patterns and expected future trajectories is essential to helping patients and their families plan for the future.

The estimated prevalence of ALS in the U.S. is around 5 per 100,000 people. Median survival from onset is 3 to 5 years, but 5% to 10% of patients survive more than 10 years. Bulbar-onset ALS, presenting initially with dysarthria or dysphagia without significant spinal involvement, along with older age at the time of diagnosis are both associated with worse prognoses. The vast majority of patients die from respiratory failure. There are two U.S. Food and Drug Administration (FDA)-approved disease-modifying medications for ALS that have been shown to have modest survival benefit: riluzole and edaravone. Riluzole, a glutamate antagonist that is taken orally twice daily, has been shown to increase life expectancy by approximately 2 to 3 months. Adverse effects are relatively minor and include fatigue, nausea, and hepatotoxicity. Edaravone, a free radical scavenger administered through intravenous infusion (4-week cycle with 2 weeks on and 2 weeks off), has been shown to slow the rate of functional neurological decline by 33% in a select subset of patients with low severity of illness. The main side effects include headache and gait disturbance.

Prevalence estimates of MS in the U.S. range from 150 to 362 per 100,000 individuals, although rates vary geographically. The typical MS course spans decades, and although the disease usually causes progressive disability over years, many patients will eventually die of other causes. Compared to the general population, studies have shown that patients with MS have a threefold increased risk for death and a 6- to 10-year shorter life expectancy. Deaths attributed to MS are commonly caused by infection, especially respiratory and urinary tract related, and are often associated with the immobility and disability that come with advanced disease, such as aspiration pneumonia.

The majority of MS cases are the relapsing-remitting type (approximately 85%) characterized by attacks (relapses) of new or worsening neurological symptoms followed by periods of partial or complete recovery (remission) where symptoms are stable. This phase is often followed by a secondary progressive phase with continuing gradual decline that lacks periods of improvement. Approximately 15% of patients present with primary progressive MS, which is characterized by progressive accumulation of disability without relapses or remissions. Patients with relapsing disease have been found to outlive patients with primary progressive MS by about 7 years with a twofold higher mortality risk in primary progressive MS compared to relapsing remitting MS. Disease-modifying therapies, including the injectables interferon beta-1a, interferon beta-1b, and glatiramer acetate, and the oral treatments dimethyl fumarate, diroximel fumarate, and teriflunomide, decrease the rates of relapse and disease progression in relapsing-remitting MS. More active MS is treated with the infusion therapies ocrelizumab, natalizumab, and alemtuzumab and the oral therapies fingolimod, cladribine, and siponimod. Ocrelizumab is approved for the treatment of primary progressive MS. Relapses are typically treated with corticosteroids. As with other serious progressive illnesses, effective palliative care for MS includes helping patients weigh the potential benefits and burdens of disease-modifying therapies on an ongoing basis throughout the disease course.

The prevalence of PD is approximately 572 per 100,000 among those 45 years of age and older. It is listed by the U.S. Centers for Disease Control and Prevention as the 14th leading cause of death in the U.S. PD predominantly affects older people and is characterized by gradually worsening motor and nonmotor symptoms over a period of years. There are no disease-modifying therapies currently available, but many individuals with PD derive significant benefit from dopaminergic medications. Certain surgical therapies such as deep brain stimulation may also be used to control motor symptoms. The majority of people living with PD will die from complications of their neurodegenerative disease, and common causes of death are aspiration pneumonia and falls resulting in injuries such as hip fractures and/or head trauma

PD is the most common cause of parkinsonism. In patients with rapid progression and limited response to typical therapies used in PD, a group of conditions called atypical parkinsonian disorders, including dementia with Lewy bodies, progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration, should be considered.

Relevant Pathophysiology

ALS is the most common motor neuron disease and is characterized by upper and lower motor neuron loss. This motor neuron degeneration causes progressive limb, axial, and neck weakness; dysarthria; dysphagia; and respiratory failure. The cause of ALS is unknown. Common upper motor neuron symptoms, caused by degeneration of the neural pathway above the anterior horn of the spinal cord, include spasticity, increased muscle tone, and increased deep tendon reflexes with gait instability. Lower motor neuron symptoms, including weakness, atrophy, and fasciculations, result from degeneration of nerve fibers traveling from the anterior horn of the spinal cord to the associated muscles. Bulbar symptoms such as dysarthria and dysphagia may be caused by both upper and lower motor neuron dysfunction.

MS is an inflammatory demyelinating disease of the central nervous system. Although the cause of MS is unknown, it is most widely believed to be autoimmune in origin. The disease causes inflammation, demyelination, and axonal degeneration of the central nervous system. MS may present with any variety of neurological signs or symptoms, but the most common are sensory symptoms, visual loss, and muscle weakness. Typically, sensory symptoms are described as numbness, tingling, electrical, cold, or itching. Lesions of the descending motor tracts of the spinal cord may lead to spasticity, hyperreflexia, and weakness of the legs.

PD is a complex motor system disorder associated with a wide array of nonmotor symptoms. The cardinal features of PD are tremor, rigidity, and bradykinesia. Postural instability is also a common feature of PD that generally occurs later in the disease. Like ALS and MS, the cause of PD is unknown. Dopamine depletion causes disruption of the basal ganglia circuits, resulting in bradykinesia and other parkinsonian symptoms.

Summary of Evidence Regarding Treatment Recommendations