Palliative care for Parkinson disease and atypical parkinsonian disorders

INTRODUCTION — 

Parkinson disease (PD) and other parkinsonian neurodegenerative disorders typically develop relatively slowly over several years. Affected patients and their families and caregivers 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, particularly in the later stages as death approaches.

This topic will review the palliative care aspects of PD and related neurodegenerative disorders. Palliative and hospice care of patients with advanced dementia is reviewed separately. (See "Care of patients with advanced dementia".)

EARLY DISEASE SPECTRUM — 

Parkinsonism (which refers to 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) (table 1).

Parkinson disease — PD is one of the most common neurodegenerative diseases of adulthood and a major cause of neurologic morbidity and mortality worldwide. The median age at diagnosis is approximately 70 years, and the incidence rises with age. (See "Epidemiology, pathogenesis, and genetics of Parkinson disease", section on 'Epidemiology'.)

The cardinal features of PD are tremor, bradykinesia, and rigidity. Postural instability is also common but typically develops later in the course of the disease. Other typical motor features include masked facial expression, hypophonia, micrographia, stooped posture, and gait abnormalities (eg, shuffling, short-stepped gait, freezing) (table 2). (See "Clinical manifestations of Parkinson disease".)

PD has a wide range of nonmotor manifestations, including cognitive dysfunction and dementia, psychosis, mood disorders, sleep disturbances, excessive daytime sleepiness, autonomic dysfunction, pain, and sensory disturbances (table 3). Most of these symptoms are not responsive to dopaminergic therapies used to treat motor features, and palliative care plays an important role in their management [1]. (See "Management of nonmotor symptoms in Parkinson disease" and "Insomnia, daytime sleepiness, and other sleep disorders in Parkinson disease".)

Atypical parkinsonian disorders — Parkinsonism can be prominent in neurodegenerative disorders other than PD, including DLB, PSP, MSA, and CBD, which account for 10 to 15 percent of patients with parkinsonism [2]. As in PD, the majority of patients will develop many nonmotor symptoms in the later stages of disease for which palliative care may play an important role.

●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 of patients but not in all (table 4). 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, but all manifest with the hallmark symptom of supranuclear ophthalmoparesis or ophthalmoplegia (table 5). With the most common "classic" phenotype of PSP, known as Richardson syndrome, the typical initial feature is a disturbance of gait resulting in falls. Additional clinical features include dysarthria, dysphagia, rigidity, frontal cognitive abnormalities, and sleep disturbances. The phenotype known as PSP-parkinsonism, which may be confused with 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 (table 6). Two main subtypes are described: MSA parkinsonian type (MSA-P), in which the initial symptoms are of parkinsonism, and MSA cerebellar type (MSA-C), in which cerebellar ataxia is prominent. Autonomic dysfunction may be seen in both subtypes. (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 (table 7). 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. (See "Corticobasal degeneration".)

ADVANCED DISEASE

Disease progression and prognosis — PD is a progressive neurodegenerative disease that usually shortens life expectancy. Progression of symptoms is highly variable, however, and it is not possible to predict future course of PD for a given individual at the time of diagnosis.

●Motor complications – Motor symptoms tend to be highly responsive to dopaminergic therapies early in the disease course, but motor fluctuations and "wearing off" develop in 30 to 40 percent of patients by five years and up to 60 percent by ten years. (See "Medical management of motor fluctuations and dyskinesia in Parkinson disease", section on 'Symptom spectrum'.)

●Progression of disability – A transition from disease impairment to disability (loss of independent function) generally occurs between three and seven years after diagnosis [3]. In a study of 142 patients with PD followed from 2000 to 2012, approximately 77 percent had a poor outcome (ie, death, dementia, or postural instability) at 10 years after diagnosis [4]. A small group of patients have a particularly slow rate of disease progression, maintaining balance and postural stability for ≥10 years and lacking severe disability even at ≥20 years.

●Life expectancy – Most studies suggest that mortality is modestly increased for patients with PD compared with age-matched controls [4-9]. A systematic review and meta-analysis found that mortality ratios varied widely among included studies, but nearly all showed increased mortality in PD, with a pooled mortality ratio of 1.5 [10]. Median survival from diagnosis ranged from 6 to 22 years. Increasing age and presence of dementia were associated with an increased risk of mortality.

●Cause of death – 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 [11].

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'.)

Hospice eligibility — 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. 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.

A working group sponsored by the Parkinson's Foundation has proposed guidance to identify patients who have needs that would make them hospice eligible under the United States (US) Medicare hospice benefit [12]. Based on systematic review of the literature and relevant US 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 – 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, 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). Aspiration pneumonia may be a particular indicator that death will occur soon, reflecting generalized weakness and swallowing and breathing difficulties [13-15].

•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 disease progression – 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 – Advanced dementia and meets hospice referral criteria based on US Medicare eligibility guidelines for dementia (table 8 and table 9) or other prognostic tools [16,17] (see "Care of patients with advanced dementia", section on 'Predicted life expectancy')

Recognizing that a patient may be approaching the end of life helps all involved (patient, family/caregivers, and professional) to be prepared and anticipate 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/caregivers for the loss. Ideally, preparation for advanced-stage disease and end of life care 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' below.)

COMPONENTS OF PALLIATIVE CARE

Interdisciplinary team approach — Interdisciplinary palliative care for PD 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 therapy, and nutrition consultation [18].

As the disease progresses and care becomes more complex, 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 [19]. An integrated care model with a patient-centered perspective helps to ensure a coordinated approach to care close to home, empowerment of the patient, family and caregiver support, case management, and specialist input as needed [20].

Initiating palliative care — 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 [13]. Thus, although the four-stage paradigm of PD (see 'Monitoring symptoms and progression' below) considers a fourth "palliative phase," palliative approaches should be integrated earlier in the disease course to maximize benefit and patient autonomy in decision-making. (See 'Advance care planning' below.)

Expert consensus panels have endorsed early integration of palliative care for patients with PD and related disorders [21]. Moreover, palliative care may be involved in an episodic way throughout the disease, 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 [21,22]. Care delivery may involve both primary (generalist) and secondary (specialty or subspecialty) palliative care tailored to resources and patient needs (table 10) [23]. This individualized approach may be the most appropriate way of maximizing care and quality of life for patients and families. (See "Primary palliative care", section on 'Definition of primary versus subspecialty palliative care'.)

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; eligible patients were assessed to have moderate to high palliative care needs [24]. 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. A subsequent trial showed similar although more modest benefits of a telehealth palliative care intervention delivered in coordination with community neurology practices [25].

Advance care planning — Advance care planning (ACP) is an ongoing process in which patients, their families/caregivers, 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.

ACP should not be seen as a one-time event, and preferences are not static. Rather, care plans should be revisited over time to ensure they still reflect the wishes of the person with PD. This may be particularly important when ACP is initiated early, as anticipating the wishes of the future self may be especially challenging in PD [26].

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 while they are able to do so (ie, when they can communicate clearly and have full capacity). ACP may include guidance on [18]:

●Future treatments including artificial hydration and nutrition and intensive care unit interventions

●Resuscitation status

●Place of care

●Place of death (eg, home, hospice, or hospital)

●Will

●Funeral plans

These wishes can be incorporated into an advance directive to guide health care decision-making when capacity is lost. In parallel, we encourage designation of a surrogate decision-maker, who would be called on to make real-time treatment decisions on the patient's behalf if they are no longer able to do so. Having both a surrogate and an advance directive may reduce emotional burden on the surrogate and ensure that the patient voice is represented in future decisions. (See "Advance care planning and advance directives".)

Patients with PD and their caregivers have varied perspectives, preferences, and barriers that influence engagement with ACP [27]. 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. (See 'Disease progression and prognosis' above.)

Some patients with progressive neurologic disease are reluctant to discuss the future and their wishes [21]. 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 [28]. 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 [29]. Thus, discussion about the future and planning for deterioration and end of life is often acceptable to patients and families/caregivers.

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 symptoms and progression — Planning the care of patients with PD requires regular monitoring of symptoms and disability.

Rating scales may be useful in the monitoring of patients with PD, such as the modified Edmonton Symptom Assessment System for PD (ESAS-PD) [30] or the Palliative Care Outcome Scale symptoms list for PD (POS-S PD) [31]. The ESAS-PD includes the 10 symptom domains of the ESAS (table 11) plus assessment of stiffness, constipation, dysphagia, and confusion. The use of a scale allows the main issues for patients with advancing disease to be identified and managed appropriately and to assess response to intervention.

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 [32]. 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 [33]. 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 [34].

Another paradigm divides progression of PD and atypical parkinsonian disorders into four arbitrary stages [35]:

●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 [36]. Of course, these aims are complementary, and palliative care needs may be present from the time of diagnosis. (See 'Initiating palliative care' above.)

Symptom management in early-stage disease

Motor symptoms in Parkinson disease — Levodopa is the most effective drug for the symptomatic treatment of PD and is the preferred initial therapy for most patients if symptoms, particularly those related to bradykinesia, become intrusive or troublesome (algorithm 1). Other dopaminergic therapies that may be used as initial therapy in select patients include dopamine agonists, monoamine oxidase (MAO) B inhibitors, and amantadine. (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 adjunctive medications such as dopamine agonists, catechol-O-methyltransferase (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. Amantadine can be effective for dyskinesia. (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, lesioning procedures including magnetic resonance imaging (MRI)-guided focused ultrasound, and device-assisted infusions of dopaminergic medications (eg, levodopa-carbidopa intestinal gel, subcutaneous foslevodopa-foscarbidopa, and subcutaneous apomorphine). These treatments are discussed in detail separately. (See "Device-assisted and lesioning procedures for Parkinson disease".)

Nonpharmacologic therapies play an important role in motor symptom management as well, including education; support groups and emotional support (table 12); and rehabilitative therapies including exercise, physical therapy, and speech therapy. (See "Nonpharmacologic management of Parkinson disease".)

Nonmotor symptoms in Parkinson disease — Management of the nonmotor symptoms of PD is essential to palliative care, as reviewed in detail separately:

●Mood disorders, including depression, anxiety, and apathy (see "Management of nonmotor symptoms in Parkinson disease", section on 'Depression')

●Cognitive impairment and dementia (see "Cognitive impairment and dementia in Parkinson disease")

●Psychosis, including visual hallucinations and delusions (see "Management of nonmotor symptoms in Parkinson disease", section on 'Psychosis')

●Insomnia, excessive daytime sleepiness, rapid eye movement (REM) sleep behavior disorder, and other sleep disturbances (see "Insomnia, daytime sleepiness, and other sleep disorders in Parkinson disease")

●Dysphagia, which is common and underrecognized in PD (see "Management of nonmotor symptoms in Parkinson disease", section on 'Dysphagia')

●Autonomic dysfunction, including constipation, sialorrhea, rhinorrhea, sexual dysfunction, orthostatic hypotension, and urinary difficulties (see "Management of nonmotor symptoms in Parkinson disease", section on 'Autonomic dysfunction')

●Musculoskeletal and neuropathic pain (see "Management of nonmotor symptoms in Parkinson disease")

Atypical parkinsonian disorders — There are no proven effective disease-modifying therapies for the atypical parkinsonian disorders (including DLB, PSP, MSA, and 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 in Parkinson disease' above). An interdisciplinary approach is essential.

Additional disease-specific guidance on symptom management is reviewed separately:

●(See "Prognosis and treatment of dementia with Lewy bodies".)

●(See "Progressive supranuclear palsy (PSP): Management and prognosis".)

●(See "Multiple system atrophy: Prognosis and treatment".)

●(See "Corticobasal degeneration", section on 'Management'.)

Family and other caregivers

Caregiver burden — Family and other caregivers are a key source of support and care as the disease progresses [37]. 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 by unpaid family members and friends, privately hired workers, or agency-employed workers. (See "Palliative care delivery in the home", section on 'Role of caregivers'.)

Unpaid 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 [38-40]. They may have received little information on PD [38,41], although many are ambivalent as to how much information they would like to receive, particularly about prognosis [41]. Importantly, caregivers' needs regarding information may differ from those of the person with PD. It may be necessary to consider and address the information needs of these individuals separately in order to support the caregiver role and maintain the patient/caregiver dyad.

There are many other 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 [39]. A survey of 47 family caregivers of patients with PD found that care was often done by the spouse, who received little help from other family members and professional help only late in the disease progression [40]. 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 [39]. Some may postpone their own needs; 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 [39]. One study of caregivers found that only 45 percent were prepared for the physical needs of the patient and only 53 percent were prepared for the patient's death [40]. 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 [39,40].

Caregivers may desire emotional support and information about the course of PD, future care issues, and the use of medication [37]. Many may be disinclined to relinquish care to others even though the care burden is adversely affecting them [39]. Moreover, the care provided needs to be of sufficient expertise to ensure that the support is acceptable, as inexperienced helpers may be seen negatively and be rejected by the primary caregivers [40].

Specific measures that may provide caregiver relief include the following [18]:

●Day care programs (or respite care) 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 burden of caring stressful [42]. 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 'Social and emotional support'.)

Bereavement counseling may be needed after the death of the person with PD [39], particularly if the caregiver has become isolated during end-stage deterioration and even more so after the death. Counseling may include screening for prolonged grief disorder (table 13) and appropriate referral for those at high risk. In some cases, prebereavement counseling may be appropriate and can help address current as well as anticipated loss and grief. (See "Bereavement and grief in adults: Clinical features".)

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 [39].

Support groups are invaluable for providing helpful information to families and caregivers. Support groups for PD are listed in the table (table 12). Additional support groups for atypical parkinsonian disorders include:

●Lewy Body Dementia Association

●CurePSP – North America

●The PSP Association – United Kingdom

●Mission MSA

●Multiple System Atrophy Trust – United Kingdom

Support from all professionals and volunteers involved in the care of a person with PD and their family/caregivers 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 [43].

LATE-STAGE SYMPTOMS AND HOSPICE 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 with PD and related disorders at the end of life often experience a variety of symptoms, which may include pain, worsening parkinsonism, dyspnea, nausea, anorexia, fatigue, and mood disorders.

Pain management — It is important to consider discomfort and pain from undertreated motor symptoms in patients with PD, particularly when dopaminergic therapies have been altered in the terminal phase of illness. Terminal stiffness is not commonly reported, but reduced mobility in bed may increase pressure area discomfort, while the "off" state can be associated with nonmotor discomfort. For the small percentage of patients with advanced illness at the end of life who have refractory pain, palliative sedation is an option. (See 'Parkinsonism' below and "Palliative sedation".)

Otherwise, opioid analgesics are the mainstay of treatment for patients with moderate to severe pain at the end of life. Nonopioid analgesics such as acetaminophen (paracetamol) and nonsteroidal anti-inflammatory drugs (NSAIDs) may be used for mild or moderate pain and can provide analgesia that is additive to that produced by opioids.

Parkinsonism — Reduction of antiparkinson medications is a common management strategy in patients with PD 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 parkinsonism-hyperpyrexia syndrome, which presents with hyperthermia and rigidity like neuroleptic malignant syndrome. In addition, abruptly stopping a dopamine agonist has been associated with dopamine agonist withdrawal syndrome, including symptoms such as anxiety, panic attacks, depression, sweating, nausea, pain, fatigue, dizziness, and drug craving. (See "Medical management of motor fluctuations and dyskinesia in Parkinson disease", section on 'Parkinsonism-hyperpyrexia syndrome' and "Initial pharmacologic treatment of Parkinson disease", section on 'Dopamine agonist withdrawal syndrome (DAWS)'.)

In some patients, the continuation of antiparkinson therapy is important to reduce rigidity, which, in turn, may cause pain and distress. For patients unable to swallow, three main options exist for continued dopaminergic therapy:

●Transdermal rotigotine – Rotigotine can facilitate dopaminergic therapy at the end of life when the oral route is not available but should be used cautiously due to concerns that it may be associated with terminal delirium [44]; lower doses may be as effective at managing symptoms with lower delirium rates [45].

●Apomorphine – Use of apomorphine by injection or continuous infusion is not common but can be an option when there is significant terminal stiffness and transdermal options have failed [46]. Apomorphine can cause nausea and hypotension and requires a test dose and premedication prior to treatment. (See "Device-assisted and lesioning procedures for Parkinson disease", section on 'Continuous subcutaneous apomorphine'.)

●Enteral route – For patients with a gastrostomy or nasogastric feeding tube, levodopa tablets can be crushed and given through the tube or, where available (outside the United States), converted to dispersible benserazide-levodopa capsules and dissolved in water. (See "Medical management of motor fluctuations and dyskinesia in Parkinson disease", section on 'Swallowing restrictions'.)

Dyspnea and secretions — Dyspnea and airway secretions are common in patients receiving palliative care for advanced terminal illness, including those with PD and related disorders. Symptom assessment and management are the same as in other patients with terminal illness, as reviewed in detail separately. (See "Assessment and management of dyspnea in palliative care" and "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 and related disorders at the end of life. We prefer ondansetron for central nausea because it does not carry risk of worsening parkinsonism, but use requires vigilance for worsening constipation. Domperidone (not available in the United States) may be used when gastroparesis is suspected, noting the safety concerns with prolonged use (>1 week).

Medications that can cause drug-induced parkinsonism should be avoided, particularly haloperidol, olanzapine, and metoclopramide, which have a high risk of worsening parkinsonism. Levomepromazine (which has been used successfully alongside rotigotine [45]) and cyclizine (which has been associated with dystonia) may be considered as second-line strategies with caution.

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 toward 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. (See "Palliative care: Overview of mouth care at the end of life".)

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 [47]. 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 goals of care and patient and family/caregiver preferences. (See "Stopping nutrition and hydration at the end of life", section on 'Our approach'.)

Delirium and agitation — Delirium can arise in the last hours and days of life, presenting as confusion, restlessness, agitation, and/or day-night reversal. The risk of terminal delirium in patients with PD is at the upper end of the range for all individuals who are dying (up to 66 percent); this is possibly related to dopaminergic replacement strategies [48-50]. Management is reviewed separately. (See "Palliative care: The last hours and days of life", section on 'Delirium'.)

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 [51]. Perhaps more important than specific location is the desire to feel safe in a setting where one's own needs and those of one's family and caregivers are met.

Based on mortality data in England, the most common places of death for individuals with PD and related disorders are nursing hospitals (38 percent), nursing homes (39 percent), and homes (19 percent) [52]. A small but increasing fraction of patients (2 percent) die in a hospice facility. In another population-based study examining death certificate data on patients with PD in 11 countries, hospitals were the most frequent place of death in France, Hungary, and South Korea, while nursing homes were the most frequent in the United States, Canada, Belgium, the Czech Republic, and New Zealand [53]. Homes were the most frequent place of death in Mexico, Italy, and Spain.

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; 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 [54]. 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: Parkinsonian syndromes" 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

●Parkinsonian disorders – 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 'Early disease spectrum' above and 'Advanced disease' above.)

●Role of palliative care – 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 'Components of palliative care' above.)

●Advance care planning – 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.)

●Symptom management – 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 'Symptom management in early-stage disease' above.)

●Caregiver support – 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 'Family and other caregivers' above.)

●Final stages of disease – Certain events may correlate with the final stages of disease and trigger a hospice referral, including (see 'Disease progression and prognosis' above and 'Hospice eligibility' above):

•Swallowing problems

•Recurring infection

•Marked decline in functional status

•First episode of aspiration pneumonia

•Cognitive difficulties

•Weight loss

•Significant complex symptoms

●Hospice care – 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 delirium. (See 'Late-stage symptoms and hospice care' above.)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges David Oliver, BSc, FRCP, FRCGP, who contributed to earlier versions of this topic review.