INTRODUCTION — Parkinson disease (PD) and the parkinsonian neurodegenerative disorders typically develop relatively slowly over several years. Affected patients and their families face increasing physical, psychosocial, and spiritual issues over this period of time. Palliative care has an important role in these conditions throughout the progression of disease, and particularly in the later stages as death approaches.
This topic will review the palliative care aspects of PD and related neurodegenerative disorders. Other clinical aspects of these disorders are reviewed elsewhere. (See "Initial pharmacologic treatment of Parkinson disease" and "Management of nonmotor symptoms in Parkinson disease" and "Nonpharmacologic management of Parkinson disease" and "Medical management of motor fluctuations and dyskinesia in Parkinson disease" and "Evaluation and treatment of insomnia, daytime sleepiness, and other sleep disorders in Parkinson disease" and "Device-assisted and lesioning procedures for Parkinson disease" and "Progressive supranuclear palsy (PSP): Clinical features and diagnosis" and "Progressive supranuclear palsy (PSP): Management and prognosis" and "Multiple system atrophy: Prognosis and treatment" and "Corticobasal degeneration" and "Prognosis and treatment of dementia with Lewy bodies".)
PARKINSON DISEASE AND PARKINSONISM — Symptoms and signs of parkinsonism (ie, bradykinesia, rest tremor, and rigidity) can be prominent in several neurodegenerative disorders, including PD, dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal degeneration (CBD). The average lifespan of patients diagnosed with these disorders is reduced.
Parkinson disease — PD is one of the more common progressive neurodegenerative diseases. The prevalence of PD increases with age. The cardinal features of PD are tremor, bradykinesia, and rigidity. Postural instability generally occurs late in the course of the disease. Other motor features of PD include craniofacial (eg, masked facial expression, hypophonia), visual (eg, hypometric saccades, eyelid-opening apraxia), musculoskeletal (eg, micrographia, stooped posture), and gait (eg, shuffling, short-stepped gait, freezing) abnormalities (table 1). In addition to motor involvement, PD is a complex disorder with diverse clinical features that include neuropsychiatric and nonmotor manifestations (table 2). (See "Clinical manifestations of Parkinson disease".)
The nonmotor manifestations of PD include the following:
●Cognitive dysfunction and dementia
●Psychosis
●Mood disorders including depression, anxiety, and apathy
●Sleep disturbances
●Excessive daytime somnolence
●Fatigue
●Autonomic dysfunction, including orthostasis, constipation, dysphagia, diaphoresis, urinary difficulties, and sexual dysfunction
●Olfactory dysfunction
●Pain and sensory disturbances
Treatment options for these nonmotor features of PD are limited, and palliative care may play an important role in their management [1].
Atypical parkinsonian disorders — Although PD is the most frequent cause of parkinsonism, atypical parkinsonian conditions (DLB, PSP, MSA, and CBD) account for 10 to 15 percent of patients with parkinsonism [2]. Distinguishing PD from these parkinsonian syndromes can be difficult, particularly in the early stages of disease. These conditions have overlapping features, but they usually can be differentiated based upon responsiveness to levodopa therapy and the appearance of signature features (eg, disordered eye movements with PSP, severe autonomic insufficiency with MSA, predominant early dementia with DLB, and unilateral apraxia in CBD). (See "Diagnosis and differential diagnosis of Parkinson disease".)
●Dementia with Lewy bodies (DLB) – DLB is the second most common cause of neurodegenerative dementia after Alzheimer disease and is characterized clinically by visual hallucinations, fluctuating cognition, and parkinsonism, which occurs in the majority but not in everyone. Other associated symptoms include repeated falls, syncope, autonomic dysfunction, neuroleptic sensitivity, delusions, hallucinations in nonvisual modalities, sleep disorders (particularly rapid eye movement [REM] sleep behavior disorder), and depression. (See "Clinical features and diagnosis of dementia with Lewy bodies".)
●Progressive supranuclear palsy (PSP) – PSP is an uncommon parkinsonian syndrome that can mimic PD in its early phase. PSP has several distinct clinical phenotypes. With the most common "classic" phenotype of PSP, known as the Steele-Richardson-Olszewski syndrome, the typical initial feature is a disturbance of gait resulting in falls. Supranuclear vertical ophthalmoparesis or ophthalmoplegia is the hallmark of PSP. Dysarthria, dysphagia, rigidity, frontal cognitive abnormalities, and sleep disturbances are additional common clinical features of the Steele-Richardson-Olszewski syndrome. The phenotype known as PSP-parkinsonism, which may be confused with idiopathic PD, is characterized by asymmetric onset of limb symptoms, tremor, and a moderate initial therapeutic response to levodopa. (See "Progressive supranuclear palsy (PSP): Clinical features and diagnosis".)
●Multiple system atrophy (MSA) – MSA is the collective term that has replaced the outdated entities known as olivopontocerebellar atrophy, striatonigral degeneration, and Shy-Drager syndrome. MSA commonly presents with parkinsonism, but patients also have varying degrees of dysautonomia, cerebellar involvement, and pyramidal signs. Two main subtypes are described: MSA-P, in which the initial symptoms are of parkinsonism, and MSA-C, in which cerebellar ataxia is prominent. Autonomic dysfunction may be seen in both subtypes.
The prominence of these manifestations along with symmetry of onset and poor response to levodopa suggests this diagnosis rather than PD. However, early in the course, some cases of MSA may resemble typical PD, including responsiveness to levodopa along with the presence of motor fluctuations and dyskinesia, only to evolve into the more typical profile of MSA later. Cognitive function in MSA tends to be relatively well preserved compared with PD and other parkinsonian syndromes, probably reflecting a lesser degree of cortical involvement. (See "Multiple system atrophy: Clinical features and diagnosis".)
●Corticobasal degeneration (CBD) – CBD is a rare but usually distinctive form of parkinsonism. The classic description of CBD is that of a progressive asymmetric, often unilateral (at onset) movement disorder with symptoms initially affecting one limb, including various combinations of akinesia and extreme rigidity, dystonia, focal myoclonus, ideomotor apraxia, and alien limb phenomenon. Cognitive impairment is a common manifestation of CBD and may be a presenting feature, while the typical parkinsonian motor features may be absent in the early phase only to emerge later as the disease progresses. Important cognitive features of CBD include executive dysfunction, aphasia, apraxia, behavioral change, and visuospatial dysfunction, with relatively preserved episodic memory. The distinctive clinical phenotype and the lack of clear response to an adequate trial of levodopa are typical for CBD and help to distinguish it from PD. (See "Corticobasal degeneration".)
After a disease duration of 10 or more years, the majority of patients will have developed many nonmotor symptoms (including cognitive decline, dementia and psychosis, autonomic failure, sleep-wake cycle dysregulation, as well as depression, pain, and sensory symptoms) for which there are very limited treatment options, and palliative care may play an important role [3].
ROLE OF PALLIATIVE CARE — Palliative care is an interdisciplinary medical specialty that focuses on preventing and relieving suffering and on supporting the best possible quality of life for patients and their families facing serious illness. Important aspects include the management of medical symptoms and psychosocial problems, advance care planning (ACP), and spiritual comfort [4,5].
Interdisciplinary palliative care optimally involves a movement disorders specialist, a palliative care clinician or nurse, a social worker, a spiritual advisor, and services including physical and occupational therapy, speech and language pathology, and nutrition [6]. As the care of the patient becomes more complex with disease progression, it is helpful to have a clear leader. An interdisciplinary team should define, if possible, a key contact, although a group contact may be more practical to ensure advice and support is always available [7]. An integrated care model with a patient-centered perspective may be helpful in ensuring that there is a coordinated approach to care close to home, empowerment of the patient, case management, and specialist input as needed [8].
The person with PD or a parkinsonian disorder will often depend on the support of family or professional caregivers. In turn, caregivers will need support to avoid burnout and to facilitate the needs of the patient.
Initiating palliative care — Although PD and related parkinsonian conditions are chronic diseases with a relatively slow course, the principles of palliative care are appropriate throughout the disease progression. Optimally, patients with PD and associated diseases should receive palliative care according to their particular needs, whether physical, psychosocial, or spiritual. An expert consensus review suggests that palliative care should be integrated early in the disease trajectory [9]. Moreover, palliative care may be involved in an episodic way throughout the disease progression, with increased involvement at times of symptom or psychosocial need and reduced input at other times, but with continued monitoring to determine the need for community and medical services [9,10]. This individualized approach may be the most appropriate way of maximizing care and quality of life for patients and families.
Palliative care needs may be present from the time of diagnosis, as the diagnosis of PD and related disorders has an immediate emotional impact and also heralds changes in quality of life, social role, financial standing, and caregiver burden that result from a chronic neurodegenerative condition [11].
Evidence to support the feasibility and benefits of palliative care includes a randomized trial involving 210 patients with PD and related disorders and 175 caregivers, who were assessed to have moderate to high palliative care needs [12]. Compared with standard care, patients assigned to integrated outpatient palliative care administered by a neurologist, social worker, chaplain, and nurse, with guidance and selective involvement of a palliative medicine specialist, had improved quality-of-life scores and global symptom burden, greater completion of advance directives, and lower caregiver burden by 12 months. These benefits appeared to be greater for people with greater palliative care needs. Retention in the intervention was high, with more than 80 percent of patients completing all planned visits.
Advance care planning — Advance care planning (ACP) is an ongoing process in which patients, their families, and their health care providers reflect on the patient's goals, values, and beliefs; discuss how they should inform current and future medical care; and, ultimately, use this information to accurately document the patients' future health care choices. (See "Advance care planning and advance directives".)
Patients with PD and other parkinsonian disorders may face increasing problems with communication due to impaired speech, bradykinesia, apathy, and cognitive change. ACP allows the patient to express views on the goals of care, future treatments, intensive care unit interventions, resuscitation status, the place of care, the place of death (eg, home, hospice, or hospital), their will, and funeral plans while the person is able to do so (ie, as they can communicate clearly and have full capacity) [6]. These wishes can be incorporated into an advance directive to guide health care decision-making when capacity is lost. They may also wish to appoint a surrogate decision maker, who would be able to make decisions on their behalf if they are no longer able to do so. (See "Advance care planning and advance directives".)
Patients with PD and their caregivers have varied perspectives, preferences, and barriers that influence engagement with ACP [13]. As part of the process, clinicians should inform patients about the best estimate of their prognosis (considering that there is a large element of individual variability in the natural history) and treatment options, and help them formulate treatment decisions while incorporating patient preferences and values. Some patients with progressive neurologic disease are reluctant to discuss the future and their wishes [9]. However, in a survey sent to 585 patients with PD there were 267 responses, and 94 percent of responders wanted to discuss prognosis and treatment information early and include their family in such discussions [14]. Approximately one-half wanted early discussion of ACP, while over 25 percent wanted early discussions about end-of-life care planning. Within a separate qualitative study, patients with PD and their partners expressed a desire for a comprehensive tool for future planning and suggested a "roadmap" approach as a guide to decision-making, with opportunities to discuss planning and prognosis when certain life changes occur [15]. Thus, discussion about the future and planning for deterioration and end of life is often acceptable to patients and families.
Early discussions of hospice as a care option that also include an acknowledgment of the serious and life-limiting nature of the patient's underlying disease can increase the likelihood of future hospice enrollment. (See "Hospice: Philosophy of care and appropriate utilization in the United States", section on 'Discussing hospice with patients and families/loved ones'.)
Monitoring progression — Planning the care of patients with PD requires regular monitoring of the symptoms and disability, and several clinical rating scales may be employed to assess disease progression. As an example, the Hoehn and Yahr (HY) staging scale is a simple, commonly utilized method of capturing the symptom progression in PD [16]. The original HY scale divides the typical pattern of PD progression into five stages:
●Stage 1 – Only unilateral involvement, usually with minimal or no functional disability
●Stage 2 – Bilateral or midline involvement without impairment of balance
●Stage 3 – Bilateral disease: mild to moderate disability with impaired postural reflexes; physically independent
●Stage 4 – Severely disabling disease; still able to walk or stand unassisted
●Stage 5 – Confinement to bed or wheelchair unless aided
Progression through higher HY stages correlates with motor impairment and worsening quality of life [17]. However, the HY scale is heavily weighted towards postural instability as the main marker of disease severity and does not completely assess other motor impairments of PD, nor does it provide any information concerning the nonmotor symptoms of PD.
The HY scale can be used in atypical parkinsonian disorders (ie, dementia with Lewy bodies [DLB], progressive supranuclear palsy [PSP], multiple system atrophy [MSA], and corticobasal degeneration [CBD]). Compared with patients who have PD, limited data suggest that patients with atypical parkinsonian disorders experience shorter latencies in HY stage progression, consistent with more rapid disease progression [18].
Another paradigm divides progression of PD and atypical parkinsonian disorders into four arbitrary stages [19]:
●Diagnosis, beginning with the first recognition of symptoms and problems
●Maintenance, on stable medication and without postural instability
●Complex, with increasing disability, motor and nonmotor impairments, and frequent changes in medications
●Palliative, characterized by inability to tolerate adequate dopaminergic therapy, and disabling or life-threatening comorbidities
In the final palliative phase, the main emphasis of care shifts from pharmacologic control of symptoms to measures that enhance quality of life [20]. Of course, these aims are complimentary, and as noted earlier (see 'Initiating palliative care' above), palliative care needs may be present from the time of diagnosis.
MANAGEMENT OF PARKINSON DISEASE
Motor symptoms — The major drugs available for the treatment of PD motor symptoms include:
●Levodopa
●Dopamine agonists
●Monoamine oxidase (MAO) B inhibitors
●Anticholinergic agents
●Catechol-O-methyl transferase (COMT) inhibitors
Levodopa is the most effective drug for the symptomatic treatment of PD and is the drug of first choice if symptoms, particularly those related to bradykinesia, become intrusive or troublesome. (See "Initial pharmacologic treatment of Parkinson disease".)
As symptoms become more bothersome or disabling, and motor fluctuations with dyskinesia emerge, the regimen of medications may need to be modified. Motor fluctuations are alterations between periods of being "on," during which the patient enjoys a good response to a dose of levodopa, and being "off," during which the patient experiences worsening parkinsonian symptoms. Dyskinesia consists of various types of abnormal involuntary movements, which are due to the effects of levodopa. A number of strategies may be useful for patients with PD who develop motor fluctuations and dyskinesia. In general, these include adjusting the levodopa regimen and adding adjunct medication such as dopamine agonists, COMT inhibitors, or MAO B inhibitors. Adjusting dietary protein is appropriate for those in whom a careful history reveals that protein interference is a problem. (See "Medical management of motor fluctuations and dyskinesia in Parkinson disease".)
For patients with advanced typical levodopa-responsive PD and motor fluctuations whose condition cannot be further improved by noninvasive medical therapy, device-assisted treatment options include deep brain stimulation, continuous levodopa-carbidopa intestinal gel infusion delivered through a percutaneous gastrojejunostomy tube by a battery-powered pump, and continuous subcutaneous apomorphine infusion administered by a battery-powered pump (available in some countries but not in the United States). These treatments are discussed in detail separately. (See "Device-assisted and lesioning procedures for Parkinson disease".)
Education is essential in order to provide patients with PD and their families with understanding and control over the disorder. In addition, the emotional and psychological needs of the patient and family should be addressed. Support groups are a valuable resource (table 3). Regular exercise and various physical therapy modalities offer substantial benefit for improving motor function and quality of life in patients with PD. Speech therapy may be helpful in improving speech volume and maintaining voice quality, as dysarthria and hypophonia are common manifestations of PD. No specific diet influences the course of PD, but a high-fiber diet and adequate hydration can help to reduce the constipation of PD, while large, high-fat meals that slow gastric emptying and interfere with medication absorption should be avoided. (See "Nonpharmacologic management of Parkinson disease".)
Nonmotor symptoms — Management of the nonmotor symptoms of PD, which is essential to palliative care, is reviewed here briefly and discussed in detail separately. (See "Management of nonmotor symptoms in Parkinson disease".)
●Psychosis is a frequent complication seen in PD, and it is characterized mainly by visual hallucinations and delusions. The management of psychosis in PD involves identifying and treating the underlying causes and contributory factors, which may include infection, delirium, dementia, and adverse effects of drugs, including those that are used to treat PD (algorithm 1). Psychoactive medications are potential culprits and should be reduced or stopped if possible. Stopping all potentially offending antiparkinsonian drugs is usually not an option, but dose reduction, particularly of drugs other than levodopa, can frequently be accomplished with amelioration of hallucinations and little loss of drug-related benefit. Antiparkinsonian drugs may be reduced or stopped in reverse order of their potency and effectiveness if hallucinations are causing disability, beginning with anticholinergic drugs, followed by amantadine, then COMT inhibitors, and dopamine agonists. Levodopa should be the last of a drug combination to be reduced, since it is essential in almost all patients with PD and has the best therapeutic index. Treatment with quetiapine, pimavanserin, or clozapine is an option if all other measures fail. (See "Management of nonmotor symptoms in Parkinson disease", section on 'Psychosis'.)
●Dementia occurs in the majority of patients with PD, especially in late stages. Cholinesterase inhibitors confer a modest benefit in some patients with PD and dementia, but treatment response should be monitored routinely and therapy tapered off if there are no observed benefits or if not tolerated. (See "Cognitive impairment and dementia in Parkinson disease".)
●Sleep disturbances in PD may present as insomnia, excessive daytime sleepiness, rapid eye movement (REM) sleep behavior disorder, restless legs syndrome, and periodic limb movements of sleep (see "Clinical manifestations of Parkinson disease", section on 'Sleep disorders'). The management of these problems is complex.
•The treatment of excessive daytime sleepiness in PD involves efforts to improve nocturnal sleep hygiene and to treat causes of poor nocturnal sleep due to parkinsonian bed immobility and stiffness. Pharmacologic treatments that may offer some benefit include the careful use of a bedtime dose of levodopa, daytime treatment with simulants such as modafinil or methylphenidate, or judicious use of coffee. (See "Evaluation and treatment of insomnia, daytime sleepiness, and other sleep disorders in Parkinson disease", section on 'Excessive daytime sleepiness'.)
•The management of insomnia, REM sleep behavior disorder, restless legs syndrome, periodic limb movements of sleep, and sleep-disordered breathing is discussed separately. (See "Evaluation and treatment of insomnia, daytime sleepiness, and other sleep disorders in Parkinson disease", section on 'Insomnia' and "Insomnia in palliative care" and "Rapid eye movement sleep behavior disorder" and "Management of restless legs syndrome and periodic limb movement disorder in adults".)
●Fatigue is a common symptom of PD but can be managed in some cases by exploring underlying secondary causes. Medications may be used for empiric treatment of fatigue, including amantadine and stimulants such as methylphenidate and pemoline. However, the response to these is often disappointing. (See "Management of nonmotor symptoms in Parkinson disease", section on 'Fatigue'.)
●Depression is the most common neuropsychiatric disturbance seen in PD, but there is no clear consensus regarding the use of antidepressants in patients with PD. In the absence of a clear first choice, drug selection should be based on potential advantages versus potential side effects. It seems reasonable to start with selective serotonin reuptake inhibitor (SSRI) in most patients, as the likelihood of adverse events is lower with SSRIs than with tricyclic antidepressants. Patients with PD who have apathy as a feature of depression can be treated with antidepressant medications, as there is no specific treatment for apathy or abulia in the absence of depression. Potential concerns with the use of SSRIs in patients with PD include the possibility of aggravating motor symptoms and the possibility of an adverse interaction with selegiline, an MAO B inhibitor sometimes used to treat PD. Although the use of SSRIs in PD with or without selegiline appears to be safe, caution is advised when introducing these drugs. (See "Management of nonmotor symptoms in Parkinson disease", section on 'Depression'.)
●Pain is a common symptom in PD and is often underrecognized. Use of a pain rating scale developed in patients with PD may be helpful in the clinic [21]. Pain related to musculoskeletal rigidity and bradykinesia may improve with dopaminergic medication and with deep brain stimulation, while painful focal dystonia (often induced by levodopa) can be treated with adjustment of the dopaminergic drug regimen or injections of botulinum toxin [22,23]. Mild to moderate pain that does not respond to these measures can be treated with nonopioid analgesics, such as acetaminophen and nonsteroidal antiinflammatory drugs (NSAIDs). More severe pain may require opioid analgesics in an individualized titrated dose. (See "Clinical manifestations of Parkinson disease", section on 'Pain'.)
●Nausea medications should be approached with caution, as certain drugs can worsen parkinsonism. Domperidone (not available in the United States) or ondansetron are preferred antiemetics. (See 'Final stages of disease' below.)
Autonomic dysfunction — Autonomic problems in PD include orthostasis, constipation, dysphagia, drooling, diaphoresis, urinary difficulties, and sexual dysfunction. These problems are also present in multiple system atrophy (MSA). The autonomic symptoms in MSA are generally more severe than in PD.
●Orthostatic hypotension in PD is one of the more disabling features of autonomic dysfunction. The first step in management is to modify or stop medications that can cause or worsen orthostatic hypotension (table 4), if possible [24]. Nonpharmacologic steps include increased fluid and salt intake, compression stockings, physical maneuvers (eg, abdominal binders), and exercise. Pharmacologic therapy includes medications such as fludrocortisone, midodrine, droxidopa, and pyridostigmine. (See "Treatment of orthostatic and postprandial hypotension".)
●Slowed gastrointestinal motility is a prominent nonmotor feature of PD related to autonomic dysfunction of smooth muscle contractility in the intestinal walls. Slow gastric motility can delay absorption of antiparkinson medications, and poor colonic motility is responsible for constipation, which is a common symptom in the prodromal or premotor phase of PD. Colonic motility also slows as people age [25]. The general approach to the management of constipation is reviewed separately. (See "Management of chronic constipation in adults".)
●Dysphagia in the early stages of the disease may respond to antiparkinsonian medications such as levodopa or dopamine agonists, which can improve flexibility and speed during swallowing in some patients. However, these drugs do not consistently improve swallowing in advanced stages. Swallow rehabilitation therapy and dietary modification can help patients with mild oropharyngeal dysphagia. Oropharyngeal dysphagia in patients with PD is reviewed in more detail separately. (See "Swallowing disorders and aspiration in palliative care: Definition, pathophysiology, etiology, and consequences", section on 'Parkinson disease' and "Swallowing disorders and aspiration in palliative care: Assessment and strategies for management".)
The use of enteral nutrition for patients with severe dysphagia and risk of aspiration is also an option. However, the available evidence suggests that tube feeding for patients with cognitive impairment or dementia does not improve nutritional status, prevent aspiration, or prolong life. (See "Care of patients with advanced dementia", section on 'Oral versus tube feeding'.)
●Sialorrhea or drooling is common in PD and can be treated with botulinum toxin injections into the salivary glands, oral glycopyrrolate, sublingual atropine in the form of a 1 percent ophthalmic solution, or sublingual ipratropium. (See "Management of nonmotor symptoms in Parkinson disease", section on 'Sialorrhea'.)
●Urinary difficulties related to autonomic dysfunction include urgency, frequency of micturition, and incontinence; the most common cause is detrusor hyperreflexia. These may cause distress and disability and need careful assessment, as often there is coexistent pathology contributing to the symptoms, such as prostatism in older men. There are no proven treatments for urinary incontinence in PD [26]. Intermittent catheterization may be necessary and may be a sign of deterioration and need for institutional care in advanced PD [27].
●Sexual dysfunction in PD is a complex problem that can range from underactivity to hypersexuality induced by the use of dopamine agonists. There are diverse causes, including autonomic dysfunction, motor dysfunction, mood disorders, and medication side effects. Management begins with a comprehensive evaluation for treatable causes [26]. Limited evidence suggests that phosphodiesterase-5 inhibitors may be beneficial for men with PD who have erectile dysfunction, but these medications may increase the risk of orthostatic hypotension. (See "Sexual dysfunction in older adults" and "Evaluation of male sexual dysfunction" and "Overview of sexual dysfunction in females: Epidemiology, risk factors, and evaluation" and "Treatment of male sexual dysfunction" and "Overview of sexual dysfunction in females: Management".)
MANAGEMENT OF ATYPICAL PARKINSONIAN DISORDERS — There are no proven effective disease-modifying therapies for the atypical parkinsonian disorders, including dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal degeneration (CBD), although some will respond modestly to levodopa early in the course of illness. Common supportive interventions for these disorders include nutrition consultation, speech and language therapy, occupational therapy, physical therapy, and walking aids. Physical therapy is important for fall prevention, reduction in contractures, and maintenance of mobility. Occupational therapy may promote longer independence in performing activities of daily living. Nonmotor symptoms associated with these disorders may be managed similarly to PD (see 'Nonmotor symptoms' above). An interdisciplinary approach is essential.
●For patients with DLB, nonpharmacologic behavioral therapies, when appropriate, are preferred over medications, which have a high rate of adverse effects. A treatment trial with a cholinesterase inhibitor may ameliorate cognitive and behavioral symptoms. If disabling psychotic symptoms persist after initiating treatment with cholinesterase inhibitors, cautious addition of a very low-dose second-generation antipsychotic drug (eg, quetiapine) is an option, after informing patients and caregivers of the risks, including the development of severe neuroleptic sensitivity reactions. Levodopa is used for treatment of disabling parkinsonism, beginning with low doses and slow upward titration while monitoring for increased psychosis. Rapid eye movement (REM) sleep behavior disorder often responds to low doses of melatonin or clonazepam. (See "Prognosis and treatment of dementia with Lewy bodies".)
Palliative care of patients with dementia is reviewed separately. (See "Care of patients with advanced dementia".)
●There are no treatments that alter the natural history of disease in PSP and no drugs that provide significant symptomatic benefit for motor symptoms as seen with levodopa in idiopathic PD. Eyelid crutches, alone or in combination with botulinum toxin therapy, may be useful for eyelid-opening apraxia and blepharospasm, which can be severe enough to render a PSP patient functionally blind. (See "Progressive supranuclear palsy (PSP): Management and prognosis", section on 'Management'.)
●There is no effective disease-modifying or neuroprotective treatment for MSA. Management is symptomatic. A poor or unsustained response to levodopa therapy is generally observed in patients with MSA, but some patients with clinically probable MSA do better with levodopa treatment than without it. Chronic orthostatic hypotension due to autonomic dysfunction is a frequent problem in MSA and is managed as discussed above (see 'Nonmotor symptoms' above). Depression is a common problem with MSA and may require counseling or antidepressant pharmacotherapy. Focal dystonia may be alleviated by botulinum toxin injection. Dysphagia should be monitored with respect to the need for feeding tube placement. Laryngeal stridor may benefit from nocturnal positive pressure ventilation; severe cases may necessitate tracheostomy. There are no effective medications for the cerebellar manifestations of ataxia and gait impairment. (See "Multiple system atrophy: Prognosis and treatment", section on 'Management'.)
●For patients with CBD, there are no medications that provide significant symptomatic benefit for motor symptoms as seen with levodopa in idiopathic PD. Treatment remains targeted at symptom amelioration. Baclofen and anticholinergics may be useful for rigidity and dystonia, and clonazepam is helpful in some cases for myoclonus.
Propranolol, clonazepam, gabapentin, topiramate, and primidone can be tried to treat tremor, but sustained benefit is rare. Depression is common and should be recognized early so that appropriate treatment can be implemented. For patients with cognitive dysfunction, it is reasonable to prescribe a cholinesterase inhibitor. (See "Corticobasal degeneration", section on 'Management'.)
CAREGIVER BURDEN — The person with PD or an atypical parkinsonian disorder depends on the support of family or professional caregivers as the disease progresses. In turn, caregivers will need support to facilitate the care of the patient [28]. Caregivers usually help with activities of daily living such as bathing, dressing, transferring, toileting, and eating, as well as instrumental activities of daily living such as grocery shopping and meal preparation. Such services can be provided informally by unpaid family members and friends or formally by privately hired workers or by agency-employed workers. (See "Palliative care delivery in the home", section on 'Role of caregivers'.)
Informal caregivers (eg, family and friends) caring for a loved one at home are at risk for significant emotional, physical, social, and financial stress. Family members may find the progressive deterioration difficult to cope with, especially when accompanied by reduced communication, impaired mobility, cognitive loss, and mood disorders [29-31]. They may have received little information on PD [29,32], although many are ambivalent as to how much information they would like to receive, particularly about prognosis [32]. However, there are many needs of the family caregivers as they face increasing care roles. One study found that caregivers were providing up to 13 of 17 possible activities of living with a median of six hours per day in one study, with the provision of help in toileting causing the greatest stress [30]. A survey of 47 family caregivers of patients with PD found that care was often done by the spouse, usually the wife, with little help from other family members and professional help only late in the disease progression [31]. In the months before death, help from a home health care agency or a privately paid aide was provided to 36 and 43 percent of the group, respectively.
Family caregivers may feel that they have little guidance from professionals and they may describe social isolation, feelings of helplessness, and an increase in dependence on them for the care of the person with PD [30]. Some may postpone their own needs, and often a crisis may be reached with exhaustion, resulting in an increased need for care of the person with PD, or precipitating admission to respite care [30]. One study of caregivers found that the proportion who were prepared for the physical needs of the patient or for the patient's death was only 45 and 53 percent, respectively [31]. Many (38 percent) reported that they were "somewhat or to a great deal" surprised that the patient died when they did.
CAREGIVER SUPPORT — There should be a careful balance in the support offered to family caregivers. This needs to be assessed individually, as some caregivers wish to receive more information but others are reluctant to discuss in depth [30,31]. Caregivers may desire emotional support and information about the course of PD, future care issues, and the use of medication [28]. Many may be disinclined to relinquish care to others even though the care burden is adversely affecting them [30]. Moreover, the care provided needs to be of sufficient expertise to ensure that the support is acceptable, as inexperienced help may be seen negatively and care rejected [31].
Specific measures that may provide caregiver relief include the following [6]:
●Day care programs for patients that allow the caregiver to socialize and meet their own needs
●Engaging multiple family members to assist in patient care (eg, for one-half day each week)
●Ensuring that patients sleep well
Psychosocial support may be very helpful, as many caregivers find the emotional burdens of caring stressful [33]. Referral of the patient and/or caregivers to a psychologist or social worker experienced in dealing with chronic illness is appropriate in some cases. Caregiver support groups can be a valuable forum for sharing experiences. In other instances, referral for legal, financial, or occupational counseling may be helpful. (See "Nonpharmacologic management of Parkinson disease", section on 'Support'.)
Bereavement counseling may be needed after the death of the person with PD [30], particularly if the caregiver has become isolated during end-stage deterioration and even more so after the death. Furthermore, the void after death may be deeply felt as the caregivers must face and adjust to the loss of the complicated role that they had accepted and developed, even if reluctantly, as a caregiver. The isolation is often worsened by the loss of social contact with others who were involved with providing care alongside them [30].
Support groups are invaluable for providing helpful information to families and caregivers. Support groups for PD are listed in the table (table 3). Additional support groups for related disorders include:
●Lewy Body Dementia Association
●CurePSP – North America
●The PSP Association – United Kingdom
●The Multiple System Atrophy Coalition
●Multiple System Atrophy Trust – United Kingdom
Support from all professionals and volunteers involved in the care of a person with PD and their family becomes more important as the caregiver burden increases. This support may include regular supervision, education about the disease, advice on how to cope as the patient deteriorates, and team meetings with the opportunity to discuss the feelings and issues raised in the provision of care. There is evidence that increased knowledge, the development of a team approach, and ongoing support may help to reduce the risks of emotional exhaustion and burnout [34].
FINAL STAGES OF DISEASE — Most studies suggest that mortality is modestly increased for patients with PD compared with age-matched controls. However, disease progression in PD is variable, and there are no symptoms or signs in idiopathic PD that allow a practitioner to accurately predict the future course of PD for any given individual. (See "Clinical manifestations of Parkinson disease", section on 'Disease progression and prognosis'.)
Disease progression in the atypical parkinsonian disorders is generally more rapid than in PD, but as with PD, the lifespan of individual patients is difficult to predict. (See "Prognosis and treatment of dementia with Lewy bodies", section on 'Prognosis' and "Multiple system atrophy: Prognosis and treatment", section on 'Prognosis' and "Corticobasal degeneration", section on 'Prognosis' and "Progressive supranuclear palsy (PSP): Management and prognosis", section on 'Prognosis'.)
Life expectancy and hospice eligibility — The disease progression and deterioration of PD and related diseases may be slow and may not be appreciated by the patient, family, or professional caregivers. There may be no specific change that heralds that the terminal stage may be approaching. Validated predictive tools for end-of-life prognosis are not available for PD, and it can be difficult to determine the most appropriate timing for hospice referral. (See 'Hospice care' below.)
A working group sponsored by the Parkinson's Foundation has proposed guidance to identify patients who have needs that would likely benefit from hospice/palliative care [35]. Based on systematic review of the literature and relevant United States Medicare guidelines for hospice eligibility in patients with dementia and other neurologic diseases, hospice referral should be considered in patients meeting any of the following three criteria:
●Advanced disease as manifested by any of the following:
•Critical nutrition impairment in the prior year (inability to maintain sufficient fluid/caloric intake and dehydration, or body mass index [BMI] <18, or 10 percent weight loss over six months and refusal of artificial feeding methods)
•Life-threatening complications in the prior year (recurrent aspiration pneumonia, falls with fractures, pyelonephritis, sepsis, recurrent fever, or stage 3 or 4 pressure ulcers)
•Motor symptoms that are poorly responsive to dopaminergic medications or that cannot be treated with dopaminergic medications due to unacceptable side effects and result in significant impairments in the ability to perform self-care
●Rapid or accelerating motor dysfunction (including gait and balance) or nonmotor disease progression (including severe dementia, dysphagia, bladder dysfunction, and, in multiple system atrophy [MSA], stridor) and disability (restricted to bed or chair-bound status, unintelligible speech, need for pureed diet, and/or major assistance needed for activities of daily living)
●Advanced dementia and meets hospice referral criteria based on Medicare eligibility guidelines for dementia (table 5 and table 6) or other prognostic tools [36,37] (see "Care of patients with advanced dementia", section on 'Life expectancy and hospice eligibility')
Aspiration pneumonia may be a particular indicator that death will occur soon, reflecting generalized weakness and swallowing and breathing difficulties [11,38,39]. Common causes of death include infection, often aspiration pneumonia; complications of the disease, such as after a fall; exhaustion and weight loss due to excessive dyskinesia and frailty; and other comorbidities that occur in the aging population [40].
Rating scales may be useful in monitoring the palliative care needs of patients with PD, such as the modified Edmonton Symptom Assessment System for PD (ESAS-PD) [41] or the Palliative Care Outcome Scale symptoms list for PD (POS-S PD) [42]. The use of a scale allows the main issues for patients with advancing disease to be identified and managed appropriately. The scores in advanced PD have been shown to be similar to those of patients with metastatic cancer, who benefit from palliative care [41,43].
The importance of recognizing that a patient may be approaching the end of life is in helping all involved (patient, family, and professional) to be prepared and anticipate the future needs. These issues, if not already addressed, involve everyone's awareness of the patient's end-of-life directive; planning for end-of-life supportive care, including where care and death will occur; completing any important financial matters such as a will; and preparing the family for the loss. Ideally, advance care planning (ACP) should take place much earlier in the disease course while the patient still is able to communicate clearly and has full capacity. (See 'Advance care planning' above and "Advance care planning and advance directives".)
HOSPICE CARE — Hospice provides medical care and support services to a patient with a terminal illness where the focus is on the best quality of life rather than prolonging life. The hospice philosophy aims to help patients achieve comfort and quality of life and death with dignity. The care and treatment provided are based on the patient's and family's goals and values. The hospice model is one of interdisciplinary, comprehensive team care that addresses the physical, psychological, social, and spiritual aspects of the end-of-life experience. Hospice care can be provided in hospitals, nursing homes, hospice inpatient facilities, and the home. (See "Hospice: Philosophy of care and appropriate utilization in the United States", section on 'The hospice model of care'.)
Services provided by hospice include symptom control, nursing care and support at home, psychosocial and spiritual care, respite care, and bereavement care. A key component is symptom control in advanced illness. Patients at the end of life often experience a variety of symptoms, which may include pain, worsening parkinsonism, dyspnea, nausea, anorexia, fatigue, and mood disorders. (See "Care of patients with advanced dementia".)
Pain management — Opioid analgesics are the mainstay of treatment for patients with moderate to severe pain in patients at the end of life. Nonopioid analgesics such as acetaminophen (known as paracetamol outside of the United States) and the nonsteroidal antiinflammatory drugs (NSAIDs) may be used for mild or moderate pain and can provide analgesia that is additive to that produced by opioids. For the small percentage of patients with advanced illness at the end of life who have refractory pain, palliative sedation is an option. (See "Palliative sedation".)
Parkinsonism — The continuation of antiparkinsonian therapy is important to reduce rigidity, which in turn may cause pain and distress. For patients unable to swallow, options include transdermal rotigotine and apomorphine by injection or continuous infusion. The use of apomorphine requires a test dose prior to ongoing treatment . For patients with a gastrostomy or nasogastric feeding tube, levodopa tablets can be crushed and given through the tube. For patients with dysphagia, orally disintegrating carbidopa-levodopa (Parcopa) is a potential treatment option. (See "Initial pharmacologic treatment of Parkinson disease", section on 'Swallowing restrictions'.)
Reduction of antiparkinson medications is a common management strategy in patients who are no longer receiving therapeutic benefit. Levodopa and dopamine agonists should be tapered gradually over several weeks or more, when possible. Sudden withdrawal of levodopa or dopamine agonists is not advised because of the rare precipitation of the parkinsonism-hyperpyrexia syndrome, which presents with hyperthermia and rigidity like the neuroleptic malignant syndrome. In addition, abruptly stopping a dopamine agonist has been associated with the dopamine agonist withdrawal syndrome, with symptoms that include anxiety, panic attacks, depression, sweating, nausea, pain, fatigue, dizziness, and drug craving. (See "Initial pharmacologic treatment of Parkinson disease", section on 'Parkinsonism-hyperpyrexia syndrome' and "Initial pharmacologic treatment of Parkinson disease", section on 'Dopamine agonist withdrawal syndrome'.)
Dyspnea and secretions — Among patients receiving palliative care for advanced terminal illness, the causes of dyspnea are often untreatable. However, if a treatable cause of dyspnea is found (eg, bronchospasm, pulmonary emboli, upper airway obstruction, pleural effusion), specific treatment of that process may be appropriate depending upon the invasiveness of the therapy and the patient's values and preferences. (See "Assessment and management of dyspnea in palliative care", section on 'Symptom assessment'.)
For patients who can tolerate them, nonpharmacologic interventions that may be of benefit for dyspnea include pulmonary rehabilitation (exercise training, breathing strategies such as pursed-lip breathing), ergonomics, and accommodation strategies, such as relaxation, modification of activity level, and use of a fan to blow air on the face. Chest wall and intrapulmonary percussive vibration and mechanical insufflation-exsufflation devices can be helpful for patients who have difficulty mobilizing secretions. (See "Assessment and management of dyspnea in palliative care", section on 'General measures for all patients'.)
Oxygen can be used for short-term relief in patients who are hypoxemic at rest or with minimal exertion. However, oxygen has not been shown to relieve dyspnea in nonhypoxemic patients. The use of noninvasive positive pressure ventilation (NPPV) in dyspneic patients at the end of life remains controversial because it generally requires initiation in hospital and may be life prolonging without necessarily improving quality of life. NPPV may be a reasonable choice for patients who otherwise require sedating doses of opioids to control dyspnea but wish to be as awake as possible, and for dying patients who wish to forestall death briefly for a specific goal. Before such treatment is initiated, the goals, timeframe for reevaluation, criteria for continuation, and plan for eventual withdrawal of NPPV should be discussed. For patients receiving palliative care who have distressing dyspnea, systemic opioids are the first-line agents. For patients with dyspnea that is refractory to opiates or accompanied by anxiety, benzodiazepines may be a useful adjunctive therapy. (See "Assessment and management of dyspnea in palliative care", section on 'Management'.)
For patients at the end of life with severe dyspnea that cannot be relieved with standard measures, the use of palliative sedation proportionate to relief of distress, including doses titrated to achieve unconsciousness if necessary, is an accepted strategy. Palliative sedation refers to use of nonopioid drugs, including benzodiazepines, barbiturates, and propofol, to control refractory symptoms (eg, pain, dyspnea, agitated delirium). The indications for palliative sedation and its implementation are discussed separately. (See "Overview of managing common non-pain symptoms in palliative care", section on 'Palliative sedation'.)
Any patient in the final stage of life may have problems clearing secretions and develop the "death rattle." These gurgling and crackling sounds that result from increased secretions can be distressing to the family. Increased airway secretions may interfere with a patient's ability to sleep, worsen dyspnea, precipitate uncomfortable coughing spells, and predispose to infections. In addition to reassuring the patient's family, proper positioning and encouraging the family to cleanse the mouth with sponge sticks can be helpful. Discontinuing nonessential intravenous fluids or enteral feedings combined with positioning the patient on his or her side helps move the secretions out of the airway. However, in some patients discontinuing fluids or enteral feeding may not be acceptable to the family/caregiver, or these maneuvers may not be helpful. Evidence of benefit from pharmacologic interventions to dry secretions is scant. Use of glycopyrrolate is generally preferred over atropine and scopolamine hydrobromide because of fewer central effects. Outside of the United States, scopolamine (hyoscine) hydrobromide and scopolamine (hyoscine) butylbromide may be used. (See "Palliative care: The last hours and days of life", section on 'Airway secretions'.)
Nausea — High-quality data to guide the treatment of nausea are lacking for patients with PD or another parkinsonian syndrome at the end of life. Domperidone (not available in the United States) or ondansetron can be used. Medications that can cause drug-induced parkinsonism should be avoided, particularly haloperidol and metoclopramide, which have a high risk of worsening parkinsonism, and levomepromazine, cyclizine, and olanzapine. (See "Drug-induced parkinsonism", section on 'Causative drugs'.)
Hydration and nutrition — As a patient with PD comes to the end of life, there may be issues to consider about nutrition and hydration. Many families and caregivers fear their loved one will starve or suffer dehydration towards the end of life. However, the restriction of food and fluids as swallowing becomes more difficult rarely leads to significant symptoms apart from a dry mouth. Good mouth care and sips of fluids can alleviate this problem. Some nutrition and fluid may be continued if a patient has a gastrostomy, although the needs of the patient may be reduced. The use of infusions of fluid, either intravenously or subcutaneously, is debated, but there is little evidence that the continuation of clinically assisted hydration would prolong life or extend the dying process, or whether stopping hydration will hasten death [44]. However, the presence of an infusion can be unpleasant for a patient and may lead to problems such as fluid overload, increased chest secretions, and bladder/vomiting issues. Intravenous hydration and enteral feeding should be stopped if there is evidence that it is not beneficial or is deleterious to the patient. The management of these potential problems is intricately related to a patient's advance directive regarding what measures, if any, should be implemented should these circumstances materialize.
Place of death — Most people express the wish to die in familiar surroundings, such as at home or at the nursing home where they live [45]. However, this goal often is not achieved for people with PD.
●A population-based study of national mortality data from England (from 1993 to 2010) showed that for patients with PD, death at home was recorded for only 10 percent [46]. Most died in a nursing or residential care home (46 percent) or hospital (43 percent), while few died in hospice (<1 percent).
●Another population-based study in 11 countries examining death certificate data from 2008 found wide variations in the place of death from PD [47]. Hospital was the most frequent place of death in several countries, including France, Hungary, and South Korea, while nursing home was the most frequent in New Zealand, Belgium, the United States, Canada, and the Czech Republic. Home was the most frequent place of death in Mexico, Italy, and Spain.
●In a study from northeast England, the recorded place of death from PD (n = 236) from years 2008 to 2011 was in hospital (47 percent), in a nursing or residential care home (25 percent), or at home (24 percent) [48]. Of the 110 patients who died in hospital, the proportion with documented end-of-life discussions was only 9 percent. During hospital admission, rotigotine patches and apomorphine were used for only 10 percent and 2 percent, respectively, whereas a nasogastric tube was placed in 25 percent. These findings suggest that hospital admission may disrupt the patient's care, and medication may not be given as regularly as at home, with the risk of increasing disability.
The smaller numbers of patients dying at home may reflect the increasing disability and risk of dementia and confusion during the disease progression in an older adult population, when family caregivers, particularly spouses, may not be able to cope at home. There is limited evidence that good care in a nursing home can reassure the family that the move of their loved one from home was the right decision to achieve relief from the burden of direct care. In one study, nursing home residents with PD, although severely disabled, were content and had an improved quality of life [49]. Thus, nursing home care may be a good option for both patients and families.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Parkinson disease" and "Society guideline links: Palliative care".)
PATIENT PERSPECTIVE TOPIC — Patient perspectives are provided for selected disorders to help clinicians better understand the patient experience and patient concerns. These narratives may offer insights into patient values and preferences not included in other UpToDate topics. (See "Patient perspective: Parkinson disease".)
SUMMARY AND RECOMMENDATIONS
●Symptoms and signs of parkinsonism (ie, bradykinesia, rest tremor, and rigidity) are prominent in Parkinson disease (PD), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal degeneration (CBD). The average lifespan of patients diagnosed with these disorders is reduced. (See 'Parkinson disease and parkinsonism' above.)
●Interdisciplinary palliative care for PD and related disorders optimally involves a movement disorders specialist, a palliative care clinician, a social worker, a spiritual advisor, and services where appropriate, including a nutritionist and physical, occupational, and speech therapists. Palliative care needs may be present from the time of diagnosis. (See 'Role of palliative care' above.)
●Advance care planning (ACP) allows the aware patient to express views on the goals of care, future treatments, intensive care unit interventions, resuscitation status, the place of care, the place of death (eg, home, hospice, or hospital), their will, and funeral plans. (See 'Advance care planning' above.)
●Management of the motor, nonmotor, and autonomic symptoms of PD and related disorders is complex. It requires careful assessment and involvement of the multidisciplinary team to help the patient, family, and caregivers maintain the best quality of life and to uphold their wishes and aims. (See 'Management of Parkinson disease' above and 'Nonmotor symptoms' above and 'Autonomic dysfunction' above and 'Management of atypical parkinsonian disorders' above.)
●Caregivers are at risk for significant emotional, physical, social, and financial stress. Specific measures that may provide caregiver relief include providing day care programs for patients that allow the caregivers to socialize and meet their own needs, engaging multiple family members to assist in patient care, offering respite care, and ensuring that patients sleep well. (See 'Caregiver burden' above and 'Caregiver support' above.)
●Disease progression in PD is variable, with few good predictors. Atypical parkinsonian disorders generally progress more rapidly than PD, but as with PD, the lifespan of individual patients is difficult to predict. However, certain events may correlate with the final stages of disease and trigger a hospice referral, including (see 'Final stages of disease' above):
•Swallowing problems
•Recurring infection
•Marked decline in functional status
•First episode of aspiration pneumonia
•Cognitive difficulties
•Weight loss
•Significant complex symptoms
●Hospice provides medical care and support services to a patient with a terminal illness where the focus is on symptom control and quality of life rather than prolonging life. Patients at the end of life often experience a variety of symptoms, which may include pain, worsening parkinsonism, dyspnea, nausea, anorexia, fatigue, and mood disorders. (See 'Hospice care' above.)
