# PALLIATIVE CARE IN NEUROLOGY

EDITED BY : Raymond Voltz, Marianne de Visser and David Oliver PUBLISHED IN : Frontiers in Neurology

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ISSN 1664-8714 ISBN 978-2-88963-471-2 DOI 10.3389/978-2-88963-471-2

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# PALLIATIVE CARE IN NEUROLOGY

Topic Editors:

Raymond Voltz, Center for Palliative Medicine, University Hospital Cologne, Germany Marianne de Visser, Amsterdam University Medical Centre, Netherlands David Oliver, University of Kent, United Kingdom

Over the last 50 years palliative care has usually been associated with cancer patients but more recently there has been increased discussion of the role of palliative care for neurological patients.

In the past years, neurology has moved from being a purely diagnostic area to a very therapeutically active one. A further step needs to be taken to modify the therapeutic activity from "cure" to "care" depending on the patient's disease trajectory. Palliative care has been associated with care at the end of life, whereas it may be appropriate earlier in the disease progression, and will extend after death in the support of bereaved families. The care of patients with neurological disease, and their families, will encompass the psychological, spiritual and existential issues and neurologists, and the teams in which they work, should develop skills to consider all aspects of care, in order to maximize the quality of life of all involved, and enable patients to die peacefully.

Citation: Voltz, R., de Visser, M., Oliver, D., eds. (2020). Palliative Care in Neurology. Lausanne: Frontiers Media SA. doi: 10.3389/978-2-88963-471-2

# Table of Contents

*69 Death Anxiety and Depression in Amyotrophic Lateral Sclerosis Patients and Their Primary Caregivers* Marvin R. Grabler, Ute Weyen, Georg Juckel, Martin Tegenthoff and Paraskevi Mavrogiorgou-Juckel

Katharina M. Lex, Philip Larkin, Jürgen Osterbrink and Stefan Lorenzl

*90 Dementia and Parkinson's Disease: Similar and Divergent Challenges in Providing Palliative Care*

Jenny T. van der Steen, Herma Lennaerts, Danny Hommel, Bertie Augustijn, Marieke Groot, Jeroen Hasselaar, Bastiaan R. Bloem and Raymond T. C. M. Koopmans

*103 Supportive Care Needs in Glioma Patients and Their Caregivers in Clinical Practice: Results of a Multicenter Cross-Sectional Study* Mirjam Renovanz, Dorothea Maurer, Heike Lahr, Elke Weimann, Monika Deininger, Christian R. Wirtz, Florian Ringel, Susanne Singer and Jan Coburger

*112 Palliative Care for Stroke Patients and Their Families: Barriers for Implementation*

Tobias Steigleder, Rainer Kollmar and Christoph Ostgathe

*120 The "Surprise Question" in Neurorehabilitation—Prognosis Estimation by Neurologist and Palliative Care Physician; a Longitudinal, Prospective, Observational Study*

Markus Ebke, Andreas Koch, Kim Dillen, Ingrid Becker, Raymond Voltz and Heidrun Golla

Wenke Grönheit, Stoyan Popkirov, Tim Wehner, Uwe Schlegel and Jörg Wellmer

*147 Improvement of Restless Legs Syndrome Undertreatment of Cancer Pain With Morphine and Fentanyl*

Jan Gärtner, Karin Jaroslawski, Gerhild Becker and Christopher Boehlke

# Editorial: Palliative Care in Neurology

### David Oliver 1 \*, Marianne de Visser 2 and Raymond Voltz 3

1 Tizard Centre, University of Kent, Canterbury, United Kingdom, 2 Amsterdam University Medical Centre, Amsterdam, Netherlands, 3 Department of Palliative Medicine, Faculty of Medicine and University Hospital, University of Cologne, Köln, Germany

Keywords: palliative care, neurology, collaboration, ethical issues, quality of life

**Editorial on the Research Topic**

### **Palliative Care in Neurology**

The role of palliative care for people with progressive neurological disease has been increasingly discussed over the last 20 years (1–3). Initially, the focus was on amyotrophic lateral sclerosis (ALS) which "represents a paradigm for palliative care in neurological diseases" (4). Indeed, progression in ALS is rapid, leading to severe disability, rendering the patients fully dependent on the support of carers, and death occurs ∼3 years after disease onset in half of the patients. More recently a palliative care approach also found its way to diseases such as high-grade glioma of which the course is also relentlessly progressive like in ALS, Parkinson's disease (PD), and multiple sclerosis (MS). The two latter are also associated with progressive disability and a shortened life expectancy but have a more prolonged and thus unpredictable course.

The European Academy of Neurology (EAN), in collaboration with the European Association for Palliative Care (EAPC) have produced a Consensus paper on neurological palliative care, which outlines the need for a wider assessment of patients—physical, psychological, social and spiritual, and including consideration of end of life care and discussion of hastened death (3). Moreover, the support of carers, both family and professional has been emphasized (3).

This Research Topic has aimed to look at new developments in the palliative care of patients with neurological disease and the editors were heartened by the response and the papers submitted. They consider many different aspects of care and several different disease groups.

The need to assess carefully the various symptoms of all patients is emphasized in the paper by Anneser et al.. They found that neurological symptoms were common, both in patients with neurological diseases and other patients receiving palliative care. These symptoms may affect the quality of life of patients. However, the survey of neurologists in the Netherlands (Walter et al.) showed that discussions about treatment restrictions and the consideration of palliative care in PD and MS were often delayed until the later stages of the disease progression—cognitive decline was often the trigger. This has again shown that education of neurologists is important in enabling discussion about deterioration and end of life to take place earlier in the disease progression, as was suggested by the EAN/EAPC paper (3).

One way of enabling professionals to become more aware of the prognosis of the patient may be the use of the "Surprise Question"—"Would you be surprised if your patient would die in the next 12 months?" This was found to be useful, particularly when combined with an assessment of the symptom burden (Ebke et al.). There is also a need to ensure that the necessary expertise in the management of palliative care issues for neurological patients is more widely available. The innovative use of telemedicine in Bavaria, Germany was shown to help and support palliative care teams in the management of patients with neurological disease, when they do not have the specific expertise required (Weck et al.).

The role of palliative care for patients with ALS has been established for many years (5). The physical aspects may be complex and in particular the use of non-invasive ventilation (NIV)

### Edited and reviewed by:

Sean Ruland, Loyola University Medical Center, United States

> \*Correspondence: David Oliver

<EMAIL_ADDRESS>
### Specialty section:

This article was submitted to Neurocritical and Neurohospitalist Care, a section of the journal Frontiers in Neurology

Received: 29 November 2019 Accepted: 11 December 2019 Published: 09 January 2020

### Citation:

Oliver D, de Visser M and Voltz R (2020) Editorial: Palliative Care in Neurology. Front. Neurol. 10:1370. doi: 10.3389/fneur.2019.01370

**5**

for patients with respiratory muscle weakness was shown to be associated with improved QoL and survival (6), albeit many questions remained about timing and the minimum forced vital capacity (FVC). Khamankar et al. present a new approach to commencement of NIV with a protocol suggesting initiation for patients with a FVC of 80% or less, a higher level than is usually suggested, together with encouragement for regular usage and cough assistance. This approach would seem to improve survival- −30.8 months in their cohort, compared to a standard regime. This is a challenge to look carefully at how NIV is discussed and used.

The psychosocial issues for people with ALS are profound, facing a progressive deterioration in physical function over a short period of 2–3 years. Grabler et al. have shown that although depression, anxiety, and death anxiety are not particularly common in ALS patients, they found that they widely correlate with each other and should be addressed altogether. Caregivers' strain was related to both depression and anxiety. This again shows the importance of the care and support, and often intervention, for caregivers, to help them care for patients with ALS. A group in Leipzig in Germany are developing a shortterm intervention "Managing Cancer and Living Meaningfully (CALM)" which has been adapted for patients with ALS (Oberstadt et al.). This now needs to be validated to ascertain if this approach would be helpful in allowing patients to receive the support they need, both in terms of symptoms, relationships, and psychosocial well-being. The use of high technology alternative and augmentative communication systems is often very important as communication becomes difficult and Linse et al. discuss the issues of ensuring that equipment is used effectively to help patients strengthen self-determination, improve quality of life and reduce caregiver burden.

There is increasing interest in the role of palliative care for people with Parkinson's disease. The paper from Hanover, Germany shows that the quality of life of people with PD is poor, with motor deficits, impairment of daily living, depression and cognitive loss (Klietz et al.). However, although 72% had an unmet palliative care need, only 2.6% had received palliative care input. A new approach is described by Eggers et al. where in Cologne, Germany a network has been developed, with a model of care provided by a movement disorder neurologist and a PD nurse collaborating with neurologists across the area. This service did not seem to see late-stage disease patients and there appeared to be poor access and loss of follow-up toward the end of life. Many PD patients may be admitted for nursing home care as the disease progresses. Lex et al. looked at residents who are in a late stage of Parkinson Disease in residential care in Salzburg, Austria, and found that despite their severe disease, limiting their activities and mobility, they did not have a significant symptom burden and were content with their quality of life. They appreciated the closeness of family and nursing home care and family members were often reassured that the resident was being cared for and their anxiety and burden had lessened.

van der Steen et al. have shown that people with PD and those with dementia face uncertainty and increasing disability and cognitive loss and that palliative care can be helpful. There is a need to develop a palliative care approach to cope with the variable and protracted deterioration, ensuring symptoms are managed effectively, carers are supported and advance care plans are considered earlier.

Although in the past palliative care for neurological patients has tended to focus on ALS, and to a lesser extent PD and MS, there is increasing awareness of the role for other disease groups. Stroke is a very common cause of disability and death across the World and there is a need to look at this patient group and their palliative care needs (7). Steigleder et al. consider the challenges of providing care for stroke, when the outcome is uncertain and there may be rapid changes. They argue for a wider consideration of palliative care and consider the barriers of the implementation of this, and look at possible ways forward. Patients with high-grade glioma also face an uncertain future and the paper from Renovanz et al. shows that both patients with glioma and their carers have many psychological issues, particularly when receiving chemotherapy. They press for greater support of both patients and carers at these difficult times.

Many patients receiving palliative care may have neurological symptoms which need to be assessed and addressed. Grönheit et al. discuss the difficult area of managing epileptic seizures and status epilepticus and provide practical advice on medication and the mode of administration. Restless legs can be a very distressing symptom, for both person and bed partner. Gärtner et al. provide an interesting insight with a case study of a patient who responded to morphine. There is still much to learn and case studies may give us an insight, which can in turn lead to a deeper understanding and more effective management of symptoms.

The papers in this volume provide an opportunity to look at palliative care for neurological patients. This is expanding and in the USA the concept of neuro-palliative care is increasing—neurologists with extra palliative care training and experience, who are able to develop the multidisciplinary approach to people with neurological diseases (8). There are many challenges and all involved in the care of patient with neurological disease—neurologists, rehabilitation physicians, the wider multidisciplinary teams, palliative care specialists, primary care teams, patients and families—need to face these issues, and may require training to cope with the new areas (3). However, with the increase in a generalist palliative care approach listening to patients, helping to set goals and assessing all areas of care (physical, psychological, social, and spiritual) and collaborating with specialist palliative care services for more complex areas we can all learn to help patients with neurological diseases, to maintain their quality of life and enable a better quality of death (9, 10).

# AUTHOR CONTRIBUTIONS

All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.

# REFERENCES

**Conflict of Interest:** The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2020 Oliver, de Visser and Voltz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

# Neurological Symptoms in Palliative Care Patients

### *Johanna Anneser1 \*, Victoria Arenz1 and Gian Domenico Borasio2*

*1Palliative Care Team, Department of Psychosomatic Medicine and Psychotherapy, Klinikum rechts der Isar, Technical University Munich, Munich, Germany, 2Service de Soins palliatifs et de support, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Lausanne, Switzerland*

Background: Neurological expertise in palliative care may be required not only for patients with primary neurological disorders but also for patients with non-neurological diseases suffering from burdensome neurological symptoms. The aim of this study was to determine the prevalence of neurological diagnoses and symptoms in palliative care patients, as well as the related burden and impact on everyday life.

### *Edited by:*

*David John Oliver, University of Kent, United Kingdom*

### *Reviewed by:*

*Teneille Emma Gofton, University of Western Ontario, Canada Deepa Bhupali, University of Illinois at Chicago, United States Idris Baker, Abertawe Bro Morgannwg University Health Board, United Kingdom*

> *\*Correspondence: Johanna Anneser<EMAIL_ADDRESS>
### *Specialty section:*

*This article was submitted to Neurocritical and Neurohospitalist Care, a section of the journal Frontiers in Neurology*

*Received: 07 February 2018 Accepted: 09 April 2018 Published: 25 April 2018*

### *Citation:*

*Anneser J, Arenz V and Borasio GD (2018) Neurological Symptoms in Palliative Care Patients. Front. Neurol. 9:275. doi: 10.3389/fneur.2018.00275*

Methods: We analyzed retrospectively the medical records of 255 consecutive patients from a tertiary medical center, at the time point of referral to an inpatient palliative care consultation service. In addition, 100 patients prospectively answered a questionnaire which included the assessment of neurological symptoms, as well as numeric rating scales for quality of life, symptom-specific burden, and restrictions in everyday life.

Results: Forty-one patients (16%) suffered from a primary neurological disease. Most decisions regarding the termination of life-sustaining measures concerned this group (20/22, 91%). Neurological symptoms (excluding pain) were documented in 122 patients (48%) with an underlying non-neurological disease. In the questionnaire study, 98/100 patients reported at least one neurological or neuropsychiatric symptom, most frequently sleeping problems (*N* = 63), difficulty concentrating (*N* = 55), and sensory symptoms (*N* = 50). Vertigo/dizziness (*N* = 19) had the greatest impact on everyday life (7.57/10 ± 2.17) and the highest symptom-specific burden (7.14 ± 2.51). Difficulty concentrating (restrictions in everyday life/burden) and pain intensity were the only symptoms significantly correlated with quality of life (*r* = −0.36, *p* = 0.009/*r* = −0.32; *p* = 0.04; *r* = −0.327, *p* = 0.003).

Conclusion: Neurological diseases and symptoms are frequent among palliative care patients and are often associated with a high symptom burden, which may severely affect the patients' lives. It is thus of paramount importance to implement neurological expertise in palliative care.

Keywords: palliative care, neurological symptoms, prevalence, symptom burden, quality of life

# INTRODUCTION

Palliative care aims to provide physical, psychosocial, and spiritual care for terminally ill patients and their families. Although differences between countries exist, palliative care has been linked traditionally to oncological diseases and internal medicine/oncology specialists still constitute the largest part of the palliative care workforce in many countries (e.g., Germany, USA, Japan, and

**8**

Canada) (1–4), while neurologists constitute less than 3% of physicians that are certified in palliative care (1, 2, 4). On the other hand, neurological and neurosurgical diseases have been found to be the second most common conditions in patients seen by a palliative care inpatient consultation service (5) and the most common diagnostic group in patients with non-malignant diseases (6).

Several reviews advocate a better integration of palliative care in the overall care of patients with neurological diseases (7–9). Both neurological and palliative care expertise are required, e.g., for patients with intracranial processes in order to assess prognosis, to substantiate decisions on the withholding or withdrawal of life-sustaining measures and to help the family understand the nature of an imminent persistent vegetative state or brain death. Although care concepts for people with motor neuron diseases may be an encouraging example of the successful integration of palliative care and neurology, many patients with neurodegenerative, neuro-oncological as well as neurovascular diseases still have a wide range of unmet palliative care needs (9, 10).

In addition, neurological expertise is required for nonneurological palliative care patients suffering from neurological symptoms. Scarce data are available on the prevalence of neurological symptoms in a general palliative care population and most of the data have been assessed retrospectively. In a metaanalysis looking at symptom prevalence in a total of 25,000 patients with incurable cancer (11), "neurological symptoms" (without further specification) were documented in 15% of all patients and in 34% within their last 2 weeks of life. Even less is known about the relevance of neurological symptoms for the patients' lives (e.g., their subjective burden, the impact on patients' quality of life (QoL), or possible restrictions in the patients' everyday lives). We therefore combined a review of patient charts with a prospective questionnaire study in order to gain an overview of the frequency of neurological symptoms as well as their clinical relevance in a general palliative care population.

# MATERIALS AND METHODS

### Retrospective Chart Analysis

The charts of 255 consecutive patients who had been referred to the palliative care inpatient consultation service, were analyzed. Data were collected over a period of 9 months. Demographic data, diagnosis, reasons for current admission to the hospital, previous treatments as well as neurological and neuropsychiatric symptoms and preconditions—as listed in the patient charts prior to the referral to the palliative care team—were assessed.

## Prospective Questionnaire Study

A total of 100 consecutive inpatients, referred to the palliative care inpatient consultation service, who were willing to participate and able to give their written informed consent were included in the questionnaire study. The questionnaire was administered in the form of a structured interview. The specific symptom burden is the degree to which the patients' everyday lives were compromised by a symptom and the patients' overall QoL were assessed using 0–10 point numeric rating scales (NRSs). NRS is a validated measure for QoL and is considered to assess the patient's general QoL rather than only its healthrelated aspects (12).

In order to differentiate lightheadedness or pre-syncopal syndromes from vertigo/dizziness, we asked the patients for the sensation of spinning/swaying and/or unsteady gait.

Actual pain intensity was assessed using a visual analog scale (VAS). To be able to compare the symptom "pain" with other neurological/neuropsychiatric symptoms, we assessed also the symptom-specific burden and restrictions in everyday life due to pain. Neuropathic pain was diagnosed by clinical assessment of the pain characteristics and the association with typical symptoms in the same area (e.g., tingling, numbness).

The "Confusion Assessment Method" (CAM) questionnaire was used when delirium was suspected. The CAM is a validated instrument for the diagnosis of delirium in a variety of medical settings (13, 14).

The Patient Health Questionnaire (PHQ-4) was used to screen patients for anxiety and depression.

In addition, patients were asked to name the symptoms, which were currently most distressing to them (max. 5). All patients who agreed received a structured neurological examination. Diagnostic workup of burdensome neurological symptoms was offered if indicated (e.g., neuro-otologic tests in patients with vertigo/dizziness). In addition, all patients were offered psychological support if desired. Descriptive statistics was performed using SPSS 24 (IBM, Chicago, IL, USA). Correlation analysis (Spearman's rho) was performed. The study was carried out in accordance with the recommendations of the Ethics Committee of the Technical University Munich. The protocol was approved by the Ethics Committee of the Technical University Munich (No: 5682/13). All subjects gave written informed consent in accordance with the Declaration of Helsinki.

# RESULTS

### Analysis of Patient Charts Reasons for Admission to the Hospital as Documented in the Patient Chart

Patients from nine different departments had been referred to the palliative care inpatient consultation service. For patient characteristics, see **Table 1**. In 84 out of 255 patients (33%), the main reasons or one of the main reasons for admission to the hospital were neurological symptoms (other than pain). 28 patients (11%) had been admitted directly to the departments of neurology or neurosurgery. The presence of neurological symptoms and preconditions—as documented in the admission examination or discovered in other examinations during the hospital stay—was assessed. Patients were assigned to one of four groups. (10 patients remained unclassified due to incomplete data or unclear assignment):

Table 1 | Analysis of patients' medical records: patients' characteristics and neurological symptoms.

### Neurological symptoms as documented in the patient chart

*Group 1: primary neurological condition, group 2: neurological symptoms presumably caused by a non-neurological underlying disease, and group 3: neurological symptoms presumably independent from the underlying disease.*

In most cases, no detailed neurological medical history had been assessed and no in-depth neurological examination had been performed before admission to the palliative care team. The most frequent neurological symptoms mentioned in the patient files are shown in **Table 1**. Neuropsychiatric symptoms such as sleeping problems, difficulty concentrating and impaired memory had not been assessed on a regular basis. "Taste abnormalities" were documented in none of the patient records.

### Termination of Life-Sustaining Measures

After palliative care consultation, life-sustaining measures had been terminated in 22 patients, and 20 (91%) of them had been classified in group I (neurological condition as primary disease).

### Patient Questionnaire Study Patient Characteristics

For the questionnaire study, 100 of 255 consecutive patients who were willing to participate and able to give their informed consent were included (50% female; 98 patients with cancer, 13 of them with brain metastases). 73 of 255 were not able to give their informed consent, 39 patients declined to participate, 32 patients could not be approached before the involvement of the palliative care consultation service, 11 lacked sufficient knowledge of the German language. None of the 41 neurologic patients could be recruited (20 were unconscious, 15 patients—mostly severe stroke or advanced glioblastoma—were conscious, but unable to consent, 5 refused to participate, and 1 lacked sufficient knowledge of the German language). 98 patients reported at least one neurological or neuropsychiatric symptom excluding pain, 38 patients stated that a neurologist or psychiatrist had treated them before admission to the hospital. Clinical neurological examination was performed after the patient interviews and objectified the symptoms reported (e.g., extent and degree of paresis or paresthesia). The values for "restrictions in everyday life" and "burden due to a specific symptom" were correlated, except for taste abnormalities.

### Prevalence of Neurological Symptoms

The prevalence of neurological/neuropsychiatric symptoms, the symptom-specific burden, and restrictions in everyday life in patients participating in the questionnaire study is shown in **Table 2**. Sleeping problems (63/100), difficulties concentrating (55/100), and sensory symptoms (50/100) occurred most frequently. In addition, several neurological/neuropsychiatric symptoms were ranked among the most burdensome overall symptoms (**Table 3**).

### Neurological Symptoms and QoL

The mean QoL (±SD) (NRS 0–10) of all patients was 3.7 (±2.3). The only neurological non-pain symptom significantly correlated to QoL was difficulty concentrating (restrictions in everyday life: *r* = −0.36, *p* = 0.009; symptom-specific burden: *r* = −0.32; *p* = 0.04). In addition, the sum scores (restrictions in everyday life and symptom-specific burden) comprising the three most frequent neurological/neuropsychological symptoms (sleeping problems, difficulty concentrating and sensory symptoms) were significantly correlated with QoL (*r* = −0.348, *p* = 0.0004; *r* = −0.322, *p* = 0.001).

### Pain

52 patients reported having only one pain localization, 27 patients reported having two, and 5 reported having three pain localizations. The most frequent type of pain was predominantly nociceptive (45 patients), followed by mixed pain (29 patients), and predominantly neuropathic pain (10 patients). Actual pain intensity—as measured by a VAS—correlated significantly with Table 2 | Prevalence of symptoms, restrictions in everyday life and burden due to specific symptoms (NRS 0–10).

Table 3 | Most distressing symptoms at the time of the interview named by 100 palliative care patients.

*Neurological and neuropsychiatric symptoms as assessed in the questionnaire study are printed in bold.*

QoL (*r* = −0.327, *p* = 0.003). Restrictions in everyday life and subjective burden due to pain did not correlate significantly with patients' QoL (*r* = −0.135, *p* = 0.21; *r* = −0.07, *p* = 0.517).

### Depression and Anxiety (PHQ-4)

Normal scores (0–2) were found in 28 patients, mild distress (3–5) in 28 patients, moderate (6–8) in 23, and severe distress (9–12) in 21 patients. PHQ-4 showed a moderate correlation with QoL (*r* = 0.271, *p* = 0.007). The PHQ-4 depression subscore was significantly correlated with the neuropsychological symptom "difficulty concentrating" (*r* = 0.361 *p* = 0.003) and moderately, but significantly correlated with QoL (*r* = –0.271, *p* = 0.007).

### Delirium

"Confusion" was documented in 47 patient charts (18.4%), 12 were able to give their informed consent to study enrollment and underwent a screening test for delirium (CAM). The test-specific criteria for the diagnosis of "delirium" were fulfilled in 11 patients. No significant correlation with regard to age or gender was found in our study group.

### DISCUSSION

Several studies investigated the presence of burdensome symptoms in patients with advanced cancer and palliative care patients [for a review, see Ref. (11, 15)]. Isolated neurological symptoms such as agitation/delirium or vertigo/dizziness have been assessed in this context. However, a systematic and detailed analysis of neurological symptoms in palliative care patients has not been carried out before. We found that almost half of the palliative care patients without a primary neurological disease had neurological symptoms documented in their charts, and 98% of patients in the prospective study reported at least one burdensome neurological/ neuropsychological symptom. This is considerably higher than previously described (11). These findings have an immediate clinical relevance in that significant suffering arises from symptoms, which are underdiagnosed and therefore insufficiently treated. Our data suggest that this may be the case for a variety of neurological symptoms, which come with a high subjective burden and/or restrictions in everyday life, e.g., vertigo/dizziness, coordination difficulties, or double vision (**Table 2**).

### Sensory Symptoms

The prevalence of sensory symptoms (numbness, tightness, tingling, and burning) reported in patients with advanced cancer and in palliative care patients varies widely from 6 to 36% (16–19). These variations may be caused by the different characteristics of the populations investigated, but also by the differing assessment methods used. Not surprisingly, it has been found that the prevalence of many symptoms is considerably lower when assessed using medical records as compared with studies using questionnaires or structured interviews (11). Correspondingly, the prevalence of sensory symptoms in our questionnaire study (50%) was markedly higher than the results from the chart reviews (9%).

### Dysgeusia

Similar results were obtained for the prevalence of "taste abnormalities" (dysgeusia) in palliative care patients: in our study, the occurrence of dysgeusia in the patients' charts was 0%, while 32% of patients in the questionnaire study reported taste abnormalities. Similarly, a previous interview study found that 86% of palliative care patients had taste abnormalities (20), while dysgeusia was documented in only 1–2% of patients' charts (17, 18).

 "Vertigo"—defined as an erroneous sense of motion and unsteadiness—is a relatively common condition, which also occurs in the general population: a survey in Germany reported a 12-month prevalence of 22.9% (21), while the point prevalence in palliative care patients with cancer was 10% (18). "Dizziness" is a term mostly used in a wider sense, which includes symptoms that range from a vague feeling of unsteadiness to severe vertigo. Pooled prevalence of dizziness in patients with incurable cancer was 17% in a previous study (11) and is similar to the occurrence found in our study (19%). Our questionnaire allowed only an initial screening for dizziness/vertigo without providing an accurate diagnosis. A detailed analysis of dizziness/vertigo in palliative care patients is urgently warranted, since effective treatment is available for many forms of this symptom (22).

### Pain

Pain had a prevalence of 84% in our palliative care population with a high symptom-specific burden and relevance for everyday life. Actual pain intensity correlated significantly with QoL, while symptom-related burden and restrictions in everyday life due to pain did not. An association between pain and QoL has been described previously, using the "brief pain inventory" (23, 24), but also an NRS (25). In contrast to the VAS assessing actual pain intensity, our items asking for a "symptom-specific burden" or "restrictions in everyday life" implicate significant elements of personal judgment and/or coping and may therefore provide different results when correlated with QoL. 39% of our predominantly oncologic—patients suffered from neuropathic pain. This matches the prevalence of neuropathic pain in cancer patients assessed in palliative care (43%) and hospice settings (35%) (26). A recent review revealed that neuropathic pain in cancer patients is often insufficiently treated because of "incorrect use of co-analgesics" (27).

### Delirium

In 47 (19%) patient charts from our cohort, "confusion" was documented. This percentage matches previous observations in a palliative care population (28). Since patients had to give informed consent to participate in the prospective study, only 12 patients underwent CAM testing in the context of our study, which was positive in 11 patients. Prevalence, diagnosis, treatment, and prognosis of confusion/delirium in palliative care patients have been widely studied (29). Recently, a randomized controlled trial showed that palliative care patients treated with standard neuroleptic medication had more delirium-specific symptoms, more side effects and a shorter survival rate than placebo-treated patients (30). This underscores the necessity of a careful diagnostic evaluation and individualized management of delirium in palliative care. Expertise in neuropharmacology and in the early detection of extra-pyramidal side effects of neuroleptic medication may be helpful to tailor treatment for these patients.

### Anxiety and Depression

Anxiety and depression are common symptoms in palliative care patients (31) with an estimated prevalence ranging between 7 and 49% (32). Correspondingly, 21% of our patients scored 9–12/12 in the PHQ, indicating severe psychological distress.

# Sleeping Problems

Similar to previous studies (33–35), sleeping problems were a frequent complaint among palliative care patients with a relatively high symptom-specific burden and impact on everyday activities. Sleep problems are multifactorial in many patients, although the moderate correlation with subjective burden due to pain suggests that inappropriate pain therapy may contribute to sleep disturbances in our patient population.

## Cognitive Symptoms

A frequent occurrence of mild-to-moderate self-reported cognitive symptoms, such as difficulty concentrating or memory disturbances, has been described previously in palliative care and cancer patients (16, 17). In addition, in a previous study, cancer outpatients named "difficulty concentrating" as one of the 13 topranked symptoms (36). Correspondingly, difficulty concentrating was the only symptom (except pain) significantly correlated with QoL in our study. A previous report showed that complaints of difficulty concentrating did not correlate with objective measurements of cognitive function in palliative care patients (37). In our study group "difficulty concentrating" correlated significantly with the PHQ-4 depression subscore. It has been shown previously that the prevalence of depression in palliative care patients and patients with advanced cancer is greater than in the general population (38). Since difficulty concentrating is a complaint which is frequently associated with depression (39), this symptom may be part of a coexisting depressive syndrome. However, cognitive impairment and difficulty concentrating may also be accompanying symptoms of CNS processes or side effects of radiation therapy [for review, see Ref. (40)]. Expertise in organic forms of cognitive impairment may be helpful for the diagnostic classification of these symptoms in order to initiate appropriate treatment.

# Neurological/Neuropsychological Symptoms and QoL

The significant correlations between the sum scores of the three most frequently reported neurological/neuropsychiatric symptoms (sleeping problems, difficulty concentrating, and sensory symptoms) and QoL, as well as the frequency at which neurological problems are reported to be one of the most distressing overall symptoms (**Table 3**), underscore the extent to which these symptoms may compromise the patients' well-being. Many neurological symptoms that turned out to be burdensome in the questionnaire study had not been assessed prior to the referral to the palliative care team. This underlines previous findings that physicians frequently tend to focus on their specialized scope of practice rather than giving sufficient attention to burdensome (e.g., neurological) symptoms in severely ill patients (41).

# Patients With Primary Neurological Diagnoses

The percentage of patients with a primary neurological diagnosis (16%) in our retrospective cohort is higher than the proportions found in previous studies (9.2 and 8.8%) (5, 6); one of which however excluded patients with primary brain tumors (5). In our study, the overwhelming majority (91%) of decisions regarding termination of life-sustaining measures (e.g., terminal extubation, termination of artificial hydration, and nutrition) were taken in patients with primary neurological diseases. This is in line with the findings of Liu et al. (6), who showed that "eliciting goals of care" was the most frequent reason for palliative care consultations among neurological patients. In-depth knowledge of the course and prognosis of neurological diseases is indispensable when discussing treatment options with the patients' families. Generally, there is an increasing awareness that many patients suffering from neurological diseases have palliative care needs (7, 8) and efforts have been made to improve the education of neurologists in this context (42).

### Neurological Expertise in Palliative Care

Given the high prevalence and the considerable burden of neurological symptoms in palliative care patients, as well as the relatively high percentage of patients with primary neurological disorders, it becomes evident that neurological expertise is crucial in palliative care. It can be fostered by increased neurological training in postgraduate palliative care education, as well as by recruiting neurologists in specialized palliative care centers. However, relatively few neurologists choose to abandon their primary specialty to concentrate on palliative medicine full-time. Clinical rotations of neurologists in palliative care teams may not only help to integrate neurological knowledge into palliative care, but also open up career options for young neurologists (2).

### Limitations

The single center design may limit the generalizability of the study. However, referral of patients from nine different departments of our university hospital resulted in a highly heterogeneous study population with a wide range of diagnoses. Our study was conducted in a tertiary medical center that has departments of neurology and neurosurgery. Therefore, the number of patients with primary neurological disorders may be higher than in less specialized hospitals. In the prospective cohort, 98% of patients suffered from cancer. The significance of the results from the questionnaire study may therefore apply primarily to oncological palliative care patients. Unfortunately, this also reflects the disproportionate prevalence of tumor patients in most specialized palliative care centers worldwide.

# REFERENCES

Similar to other centers (43, 44) patients with non-malignant diseases including primary neurological disorders were referred to our palliative care consult service only at a very late stage. These patients were unable to consent and could not recruited for the prospective study. Similarly, patients of all disease stages and neurological symptoms that affected their ability to consent (e.g., delirium) were excluded from the study. Hence, the prevalence of neurologic symptoms in a general palliative care population may be even higher and the symptoms more burdensome than found in our prospective study group.

Finally, the NRSs for the assessment of symptom-specific burden and for restrictions in everyday life used in our study had not been validated previously. However, NRSs allow for a direct comparison between specific neurological symptoms and help reducing the study burden for the severely ill patients to a minimum.

# CONCLUSION

A majority of palliative care patients in our study suffered from neurological symptoms in varying degrees, frequently causing considerable symptom burden and restrictions in everyday life. Some of these symptoms are not well documented in patient charts and may remain undiagnosed and untreated. In addition, the question of withdrawal of life-sustaining treatment is most frequently posed in patients with primary neurological diseases. In consequence, palliative care teams are confronted on a daily basis with complex neurological questions and burdensome neurologic symptoms. This underscores the importance of the neurological expertise in palliative care teams.

# AUTHOR CONTRIBUTIONS

JA was involved in the conception and design of the study, the statistical analysis and interpretation of data, and drafted the manuscript. VA was involved in the design of the study, in the acquisition of data, and approved the final manuscript. GB was involved in the conception of the study, and critically reviewed, revised, and approved the manuscript.

# FUNDING

The study has been supported by a grant no. H420 7218 9999 22190 from the "Stifterverband für die Deutsche Wissenschaft."

**Conflict of Interest Statement:** The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

*Copyright © 2018 Anneser, Arenz and Borasio. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.*

# The Role of Palliative Care in Chronic Progressive Neurological Diseases—A Survey Amongst Neurologists in the Netherlands

Hannah A. W. Walter 1†, Antje A. Seeber 1 \* † , Dick L. Willems 2 and Marianne de Visser 1

*1 Department of Neurology, Amsterdam University Medical Center, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands, 2 Section of Medical Ethics, Department of General Practice, Amsterdam University Medical Center, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands*

Background: Chronic progressive neurological diseases like high grade glioma (HGG), Parkinson's disease (PD), and multiple sclerosis (MS) are incurable, and associated with increasing disability including cognitive impairment, and reduced life expectancy. Patients with these diseases have complex care needs. Therefore, timely advance care planning (ACP) is required. Our aim was to investigate timing and content of discussions on treatment restrictions, i.e., to initiate, withhold, or withdraw treatment in patients with HGG, PD, and MS, from the neurologists' perspective.

### Edited by:

*Barak Bar, Loyola University Medical Center, United States*

### Reviewed by:

*Jeanne Teitelbaum, McGill University, Canada RajaNandini Muralidharan, Winthrop University Hospital, United States*

> \*Correspondence: *Antje A. Seeber<EMAIL_ADDRESS>
*†These authors have contributed equally to this work*

### Specialty section:

*This article was submitted to Neurocritical and Neurohospitalist Care, a section of the journal Frontiers in Neurology*

Received: *08 September 2018* Accepted: *14 December 2018* Published: *14 January 2019*

### Citation:

*Walter HAW, Seeber AA, Willems DL and de Visser M (2019) The Role of Palliative Care in Chronic Progressive Neurological Diseases—A Survey Amongst Neurologists in the Netherlands. Front. Neurol. 9:1157. doi: 10.3389/fneur.2018.01157* Methods: We performed a national online survey amongst consultants in neurology and residents in The Netherlands. The questionnaire focused on their daily practice concerning timing and content of discussions on treatment restrictions with patients suffering from HGG, PD or MS. We also inquired about education and training in discussing these issues.

Results: A total of 125 respondents [89 neurologists (71%), 62% male, with a median age of 44 years, and 36 residents (29%), 31% male with a median age of 29 years] responded. Initial discussions on treatment restrictions were said to take place during the first year after diagnosis in 28% of patients with HGG, and commonly no earlier than in the terminal phase in patients with PD and MS. In all conditions, significant cognitive decline was the most important trigger to advance discussions, followed by physical decline, and initiation of the terminal phase. Most discussed issues included ventilation, resuscitation, and admission to the intensive care unit. More than half of the consultants in neurology and residents felt that they needed (more) education and training in having discussions on treatment restrictions.

Conclusion: In patients with HGG discussions on treatment restrictions are initiated earlier than in patients with PD or MS. However, in all three diseases these discussions usually take place when significant physical and cognitive decline has become apparent and commonly mark the initiation of end-of-life care. More than half of the responding consultants in neurology and residents feel the need for improvement of their skills in performing these discussions.

Keywords: palliative care, advance care planning, nervous system diseases, decision making, Parkinson's disease, multiple sclerosis, glioma

# INTRODUCTION

Chronic progressive neurological diseases like amyotrophic lateral sclerosis (ALS), high grade glioma (HGG), Parkinson's disease (PD), and multiple sclerosis (MS) are incurable and often associated with a shortened life expectancy. Patients with these diseases have a host of unmet physical, cognitive, psychosocial, and spiritual needs and experience problems in coordination and continuity of care (1, 2). There is growing evidence that early integration of palliative care improves the quality of life of these patients and their significant others. However, realization of this integration appears to be challenging in every day practice (3–8). The presence of communication barriers, e.g., speech impairment frequently observed in ALS and PD, and cognitive or behavioral disturbances as are found in HGG, PD, and MS complicate matters even more.

Misconceptions about palliative care are common, amongst health care professionals and patients. First, palliative care is often considered to be synonymous with hospice care or end-of-life care (9). Second, illness trajectories of progressive neurological diseases vary from rapidly progressive (ALS, HGG) to prolonged and fluctuating (PD, MS). Patients with these diseases have significantly different symptom profiles, psychosocial issues, and spiritual needs (1, 10, 11). Consequently, their caregivers' burden is equally variable. Third, knowledge about palliative care needs in chronic progressive neurological diseases is just emerging (3, 12, 13). Fourth, health care professionals in general are found to not be familiar with communication skills needed to deliver bad news and to discuss advance care planning (ACP) (14–19).

ACP is a communication process in which patients' wishes, preferences, and goals with regard to future (palliative) care, including end-of-life care, are discussed in a timely, and iterative manner (20, 21). ACP includes considerations about diseaseand symptom-specific treatment, resuscitation and other lifeprolonging modalities, treatment restrictions, end-of-life wishes and appointment of surrogate decision-makers. There is an increasing body of evidence, mostly from research in patients with cancer and other non-neurological chronic progressive diseases, that ACP improves both the quality of end-of-life care, as well as patient and family satisfaction, and may reduce stress, anxiety, and depression in surviving relatives (22, 23). In ALS, the paradigmatic disease for palliative care in neurodegenerative disorders, it is common knowledge that discussions about future care should be done in an ongoing, iterative way (2, 24, 25). There is sparse evidence that in patients who are severely ill after stroke or with dementia, ACP is restricted to discussions about the care in the last phase of life (26). The same applies to ACP in patients with HGG (12, 27). Whether and how ACP takes place in long-term follow-up of patients with PD and MS has not been investigated so far.

The objective of our study was 2-folded. First, we aimed to investigate timing and content of discussions on treatment restrictions, i.e., to initiate, withhold, or withdraw treatment in the course of HGG, PD, and MS, from the neurologist's perspective. The focus was on these three conditions because in the Netherlands neurologists generally are involved in the follow-up of patients with HGG, PD, and MS, whereas specialists of other disciplines take care of patients with ALS, dementia, and post-stroke sequelae. Second, we compared our results with international data about ACP in patients with ALS.

# MATERIALS AND METHODS

# Study Design and Population

We conducted a national cross-sectional survey amongst consultants in neurology and residents in The Netherlands. For reasons of privacy, we approached the potential participants via the secretariat of the neurology departments with the request to provide the physicians with the link to the online questionnaire. In order to maximize the response rate, two reminders were sent within the following 3 months. Data collection started in February 2016 and ended in August 2016. The questionnaire focused on three progressive neurological diseases, i.e., HGG, PD, and MS.

# Ethics Approval

Dutch law specifies that ethics approval is only needed when 'participants are subject to procedures or are required to follow rules of behavior' (http://www.ccmo.nl/en/your-researchdoes-it-fall-under-the-wmo). As this was not the case, written informed consent was not required from the participants, as confirmed in a letter from the AMC local research ethics committee (REC) from 11th October 2018. Participants knew that the received data would be treated confidentially and used anonymized only, and that they could withdraw from the study at any moment, without explanation.

## Survey Questionnaire

The questionnaire was designed by the authors, partly based on the literature and partly based on the results of in-depths interviews with neurologists by one of the authors (AAS) (28). The online tool Survey Monkey (www.surveymonkey.com) was used. The questionnaire consisted of 57 questions, subdivided into three different sections. In the first section, questions were raised about the experiences of neurologists and residents with timing and content of discussions on potential treatment restrictions held with patients suffering from HGG, PD, and MS. Actually, we used the terms "considerations," "initiating," "withholding," and/or "withdrawing," and "common/accepted treatment option." In the second section, neurologists were asked to elaborate on a recent case of HGG, PD, or MS in which such discussions took place. In the third section, there were questions on education and training in communicating treatment restrictions with patients and families. The questions were either pre-structured or open-ended. Two pilots were done amongst 10 neurologists and the questionnaire was adjusted according to their feedback.

### Analysis

Data analysis was conducted by SPSS (IBM Corp. Released 2016. IBM SPSS Statistics for Windows, Version 24.0. Armonk, NY: IBM Corp). Frequencies and proportions were calculated by descriptive statistics for categorical variables. Mean and standard deviation and median and range were calculated for continuous variables. Open-ended questions were analyzed and coded by three authors (HAWW, AAS, MdV).

### RESULTS

There were 991 consultants and 341 residents who were contacted via their medical secretariats. One hundred twenty-five of them responded to the online survey, 89 (71%) consultants and 36 (29%) residents, from 63 hospitals (out of 79), yielding an overall response rate of 15% participants, but a response rate of 80% neurology practices. A total of 72 (58%) respondents (58 neurologists and 14 residents) filled in the survey completely. Therefore, the data was analyzed with a varying number of missing values.

### Profile of Respondents

**Table 1** shows the demographics of the respondents. Amongst consultants in neurology, 48 (54%) worked as general neurologist, 35 (39%) also had a subspecialty area, and 41 (46%) worked in a subspecialty area only. Twenty (22%) neurologists had specific expertise in movement disorders, 18 (20%) in neuro-oncology and 19 (19%) in MS. Within the group of residents, 25 (75%) worked in general neurology, and 15 (44%) also worked in a subspecialty area. Nine residents (26%) worked in a subspecialty niche only. Eight (22%) residents had specific expertise in neuromuscular diseases, 4 (12%) in movement disorders, 3 (9%) in neuro-oncology, 1 (3%) in MS, and 6 (18%) in vascular neurology.

The demographics of the respondents of our survey were consistent with those of the general population of neurologists in the Netherlands ("Nivel survey") (29). The median age of neurologists in our survey was 44 years (range 39–56.5), compared to 49 years in the Nivel survey. Sixty-two percent was male compared to 72% in the Nivel survey. **Figure 1** shows that the distribution of our respondents across the 13 Dutch provinces was similar to that of specialists in general1 .

\**In The Netherlands, the duration of neurological training is 6 years.*

1Available online at: https://capaciteitsorgaan.nl/app/uploads/2017/04/2017\_04\_ 24-DEF-Regionale-spreiding-medisch-specialisten.pdf

# Discussions on Treatment Restrictions: Frequency and Participants

Most consultants in neurology (n = 74, 85%) and residents (n = 32, 91%) reported to have had discussions on treatment restrictions more than once per 6 months. Thirteen percent (n = 14) of the consultants had had one or more discussions per week. Thirty-four (40%) of the neurologists reported that they had had a discussion on treatment restrictions with more than 5 patients over the past 12 months. Of the residents 37% (n = 13) had had one or two of these conversations over the past 12 months. Ninety-two percent (n = 75) of the consultants in neurology and 65% (n = 22) of the residents reported that most of the time these discussions had taken place with the patient and a caregiver, in 8% (n = 7) and 35% (n = 12), respectively, only with a caregiver, and not once with the patient only. Fiftyfive percent (n = 44) of the consultants and 53% (n = 17) of the residents reported to have had two-tiered discussions on treatment restrictions.

# Discussions on Treatment Restrictions: Timing

Eighty-seven percent (n = 59) of the consultants in neurology and 92% (n = 23) of the residents were of the opinion that a doctor should initiate the discussions. Twenty-four to 33% of our respondents replied that they initiated the discussion "when the patient brings up the subject" and 16–26% "when the patient's family brings up the subject." In PD and MS, discussions on treatment restrictions took rarely place at diagnosis, and not once within the first year of diagnosis (**Figure 2**). Seventy-one percent (n = 56) of the neurologists and 70% (n = 77) of the residents, respectively, discussed treatment considerations in the terminal stages of PD and MS. In HGG, 28% (n = 18) of the respondents discussed treatment restrictions within the first year of diagnosis, 68% (n = 60) "when physical decline started" and 61% (n = 54) in the terminal phase. "The start of cognitive decline" triggered a discussion in 8, 5, and 4% in HGG, PD, and MS, respectively, whereas "when clear cognitive decline had started" led to discussions in 56, 47, and 44% in HGG, PD and MS, respectively (**Figure 2**).

## Reflections on Discussions on Treatment Restrictions in Recent Cases

Respondents were asked to recall the most recent patient with HGG, PD, or MS with whom they had discussed a treatment restriction. Demographics and diagnosis of respondents' cases are summarized in **Table 2**. The median time since the discussion had taken place was 1 month (range 1 week−60 months). Sixty percent (n = 38) of the patients had cognitive decline and 23% (n = 15) were incompetent, of whom 13 (87%) had HGG and 2 (13%) PD. Eighty percent (n = 53) of the respondents reported that both patients and caregivers had been present during the discussions. In two instances (3%) the patient was alone, and in 4 (6%) only the caregiver was present. The mean duration of conversations was 29 (SD 13.3) min for neurologists, and 31 min (SD 14.1) for residents.

There was no consensus on the treatment policy between physician and patient or caregiver/family in 23% (n = 15) of the cases for the following reasons: "The patient was not ready to discuss the subject," "Patients' caregivers were not ready to discuss the subject," "The patient did not understand why a

treatment should be stopped" or "The patient's relatives did not understand why a treatment should be stopped". In 12 cases (80%) a follow-up appointment was planned, and in 7 cases (47%) the respondent said to have complied with the patient's or relatives' wishes.

*PD, Parkinson's disease; HGG, high grade glioma; MS, multiple sclerosis.*

TABLE 3 | Considered treatment options per disease (percentages).

\**In a small number of responses "corticosteroids" were mentioned as discussed treatment option in PD patients. Perhaps this should be considered an error, since this drug is very unusual in PD.*

# Discussing Treatment Initiation or Withdrawal

Reasons to discuss treatment restrictions varied. "Acceleration of the disease process" was the main reason in 37% (n = 22) of the respondents and "Unexpectedly severe functional decline" was mentioned in 10% (n = 6). Other reasons included "Exhaustion of the possibilities to favorably influence the disease process" in 28% (n = 11) and the "The patient brought up the issue" in 8% (n = 5) of the cases. When asked which treatment modalities were considered, respondents could choose "initiate" or "withhold/withdraw". For patients with PD, resuscitation (n = 12, 75%), ventilation (n = 12, 75%), admission to intensive care unit (n = 12, 75%), and feeding tube (n = 10, 63%) were the most discussed issues. In HGG, respondents discussed ventilation (n = 34, 79%), resuscitation (n = 33, 77%), surgery (n = 32, 74%), and admission to the intensive care unit (n = 31, 72%). In MS, disease-specific medication was discussed in five instances (71%), non-disease specific medication in four (57%) (i.e., medication for urine incontinence or anti-depressants) and admission to hospital in four (57%).

**Table 3** shows the discussions of treatment modalities (initiate or withhold/withdraw) in the specific disease groups in percentages.

When asked which terminal care options were discussed, pain alleviation was mentioned in 70% (n = 28) of the cases, alleviation of dyspnea in 55% (n = 22), and psychosocial support in 53% (n = 21) of the cases. Palliative sedation was discussed in 60% (n = 24) of the cases.

When asked if, in retrospect, the respondents would have discussed treatment restrictions earlier in the disease process, 27% (n = 17) agreed with this statement. Asked for reasons to postpone discussions the following statements were provided: "The patient could not handle it" (25%, n = 4), "I did not want to deprive hope" (19%, n = 3), "Lack of suffering of the patient" (19%, n = 3) and in one case the neurologist said it would have taken too much time.

Preferred location for terminal care was discussed by 88% (n = 36) of the respondents. The option "treatment at home" was mentioned in 42% (n = 15) of the cases, and the options "hospice" in 36% (n = 13).

### Interpretation of the Meaning of Palliative Care

Respondents were asked "What does palliative care mean in your opinion?" Amongst the 77 neurologists and residents who responded to this question, 48% (n = 37) used the word "comfort," 29% (n = 22) considered palliative care as "relief of suffering" and in 17% (n = 13) it was coded as "quality of life." "Terminal phase," "end-of-life" or "no extension of life" was mentioned in 21% (n = 16). Thirteen percent (n = 10) of respondents used the description "no cure possible" and 12% (n = 9) "symptomatic treatment." The term "supportive care" was used by 9% (n = 7).

### Education in Palliative Care

Sixty-four percent (n = 44) of the consultants in neurology and 75% (n = 18) of the residents reported that they were neither educated nor trained in discussions on treatment restrictions in chronic progressive neurological disease. Fifty-seven percent (n = 39) reported that they felt a need for education. Amongst the 25 consultants and 6 residents who were educated or trained, 14 consultants and 4 residents received this education as undergraduates, 18 consultants, and 3 residents during training, and 12 consultants on-the-job. Twenty-two consultants and 5 residents had had education via interactive lessons, for example a role-play, 13 consultants, and 2 residents had had education by supervision. Twenty one of the educated or trained consultants and 5 residents felt that their education/training had been sufficient for their work in clinical practice.

### DISCUSSION

Our survey indicates that in The Netherlands the timing of discussions on treatment restrictions in patients with three chronic progressive neurological diseases (HGG, PD, and MS) varies considerably. The consultants in neurology and residents who responded to our online survey, reported that these discussions regularly took place in the first year of diagnosis in HGG, and mostly in the terminal phase of PD and MS. In all conditions, significant cognitive decline was the most important trigger for the respondents to advance discussions, followed by physical decline, and the terminal phase.

As the response rate was rather low and selection bias might have taken place the findings of our survey have to be interpreted with caution (see also "strengths and limitations"). Importantly, the results are in line with previously reported findings that discussions on treatment restrictions in chronic progressive neurological diseases most often take place after a sudden decline of patients' condition (12, 26, 30).

In ALS, which is considered a paradigmatic disease for palliative care, rapid motor deterioration often includes bulbar impairment leading to speech impairment (31). According to (best practice) guidelines the imminent communication barrier allows no delay in initiating discussions on patients' expectations, wishes and preferences regarding treatment options/restrictions and end-of-life issues (2). There is also a rapid decline in patients with HGG, and in addition the presence of significant cognitive impairment, delirium, communication difficulties, and loss of consciousness impairs their decision-making capacities (12). Up to 79% of patients with HGG have cognitive impairment before treatment, and more than 50% lack full decision-making capacity 4 months after diagnosis (32, 33). This percentage increases, especially in the last months of life (27). However, initiating ACP from diagnosis onwards is still a matter of debate in this patient group (34). In PD and MS, cognitive impairment is also common. In PD, 60% of patients have dementia after a disease duration of 12 years, preceded by a period of mild cognitive impairment, which can even be present at diagnosis (35, 36). Frequencies of cognitive impairment in patients with MS range from 40 to 75% and can become manifest at all stages and in all subtypes of the disease (37, 38) Importantly, cognitive impairment in MS at time of diagnosis is considered a marker of most aggressive pathology (39). In the first consensus review on the development of palliative care in neurology it is therefore recommended to initiate discussions on future care options and wishes early in the course of chronic progressive neurological diseases, especially when cognitive, and communication impairment are likely to occur (40).

Literature on optimal timing of ACP in chronic progressive neurological diseases is scarce. In ALS, ongoing communication of future (palliative) care from diagnosis onwards is strongly recommended, preferably by a multidisciplinary team (40, 41). However, in practice, even in the follow-up of patients with ALS ACP appears to be regularly delayed or triggered by the occurrence of life-threatening complications (30, 42). It is of note that there is a perceived lack of awareness of advance directives amongst health care professionals, in particular hospital staff, which obviously limits the effectiveness of such documents (43, 44). Advance directives are equally underutilized by patients since a study found that only 30% patients with ALS complete them (7). To support both physicians and ALS patients to be better prepared, the recently published NICE guideline recommends to offer patients with ALS the opportunity to discuss their treatment preferences and concerns about care at the end of life at trigger points such as "at diagnosis," "if there is a significant change in respiratory function," or "if interventions such as gastrostomy or non-invasive ventilation are needed" (2). Regarding the timing of the discussions, the guideline also advises to take into account the person's current communication ability, cognitive status, and mental capacity. These recommendations are partly based on interviews with patients or (bereaved) caregivers' views. They want sufficient information to be able to take well-considered decisions, as it gives them a feeling of having choice and control over their treatment (14, 45, 46). Timely discussions on end-of life care, options and preferences, have also been shown to lower anxiety, and distress in ALS patients and their caregivers (44).

In the first guideline of the European Association for Neuro-Oncology for palliative care in adults with glioma ACP is defined as a process which is 'concerned with [. . . ] preferences related to non-treatment decisions or preferred place of death. The guideline stresses that ACP is most effective when it is started in a timely fashion, allowing patients, caregivers, and physicians to proactively address the challenges together during the course of the disease'(12) . Indeed, there is growing awareness of the importance to openly communicate about patients' expectations, wishes, and preferences during the entire disease trajectory (34). However, in daily practice ACP in patients with HGG is still closely linked to the terminal phase, concerning both timing and content (47). Up to 40% of patients with HGG seem not to be involved in any end-oflife discussion, and the timing of end-of-life discussions may vary widely (1–140 days) (48). A retrospective study amongst physicians on end-of-life decision-making in patients with HGG showed that important topics were life-prolonging treatment (38%), admission to hospital (49%), palliative sedation (29%), and euthanasia (38%). Treatment was withheld in 29% of patients and concerned medication (antibiotics, dexamethasone), radiotherapy, placement of ventricular drain, and artificial administration of food or fluids (27). In our survey the most discussed topics were "resuscitation," "invasive ventilation," and "admission to ICU." One reason for these differences might be that we tried to avoid focusing on the last phase of life in our survey.

In contrast to both ALS and HGG, PD and MS are slowly progressive diseases with an often fluctuating course, unexpected declines, and gradual accumulation of impairments causing significant unmet needs (10, 49, 50). Recently, a study on preferences of patients with PD for communication about ACP showed that most (but not all) of them want prognosis and treatment information early, and that many expect their healthcare providers to bring up these issues (51). A qualitative study involving patients with PD underlined this: about half of the interviewees wanted their neurologist to raise the subject of ACP as an adjunct to usual care (49). And a survey amongst surrogates of patients in advanced stages of PD indicated that living wills might be completed by up to 94% of the patients, but shared with a physician by only 38% of them (52).

In a survey study on MS patients' palliative care needs the majority of respondents found it important to address the progression of disease and ACP. More than one-third wished to talk about end-of-life issues (53). One study addressing longterm care planning showed that on average only 11% healthcare providers discussed this issue, ranging from 10 to 26% for mildly affected and severely affected patients, respectively (54).

Currently, there are efforts being made to incorporate palliative care principles in PD and MS patients' long-term follow-up (1, 7, 8, 40). In line with that, the use of triggers to identify significant deterioration has been suggested, and end-of-life care needs are being mapped (15, 55). Pertinent topics to discuss in advanced PD and MS should include tube feeding, the use of antibiotics in case of infection, non-invasive ventilation in case of respiratory failure, and resuscitation (56).

In our survey, the most discussed treatment options with PD patients or their caregivers were "resuscitation," "invasive ventilation," "admission to ICU," and "use of a feeding tube." In MS the issues of "disease-specific medication" and "nondisease specific medication" and "admission to hospital" were most frequently discussed. Due to the small sample size (PD = 16, MS = 7) it is not possible to draw any conclusions about this discrepancy.

The results of our survey suggest that in most cases the consultants in neurology decided on the timing of discussions on treatment restrictions, and indeed the respondents were of the opinion that a doctor should initiate these conversations. However, they also appeared to be sensitive to the wishes of the patient or the patient's family if they brought up the subject. Uncertainty about optimal timing often causes postponement of discussions on treatment restrictions (57). In our survey reasons to postpone discussions included "I did not want to deprive hope" and "The patient could not handle it." A "wait and see policy" concerning discussions about the appropriate amount of future care seems to be a quite common strategy of many healthcare professionals (58–63).

At the end of our survey, we asked via an open-ended question what "palliative care" meant to the participating consultants in neurology and residents. There was a great variety of responses of which the terms "comfort," "quality of life," "end-of-life care," and "terminal care" were mentioned most frequently. This is consistent with previous research amongst health care professionals, including neurologists (1). One common misconception is that discussions on future (palliative) care may signal the 'beginning of the end', despite the finding that usual neurological care during follow-up of patients with chronic progressive diseases can go hand in hand with palliative care, including ACP (9, 64). The term "palliative care" is not only confusing for neurologists, but also for patients who might not be interested in "palliative care," but willing to attend a team-based clinic providing intensive symptom management and psychosocial support (15). Therefore, some clinicians suggest to talk about "supportive care" (65). In our survey 7% of the consultants in neurology associated palliative care with supportive care.

In our study, most neurologists reported that they were experienced in having discussions on treatment restrictions, i.e., not initiating or withdrawing treatment. However, when asked about their education 66% of the respondents reported that they had not been educated or trained in having these conversations, and about half of them indicated that they felt a need for education on this topic. Those who were trained felt that it was sufficient for daily practice. Various authors have described a general lack of education in palliative care skills amongst physicians, residents, and students (15, 66–70). A recent study investigating the effectiveness of training in palliative and endof-life communication skills in medical students showed that nearly 80% indicated retention of communication skills after 1 year with regard to "giving bad news," followed by "talking about death and dying," and "end-of-life preferences/do not resuscitate" in 40–45% of the students (71). Overall, there is quite some evidence that communication training improves discussions on diagnosis, treatment options, and preferences including end-oflife care as experienced by both healthcare professionals and patients with progressive diseases and their caregivers (16, 72– 76). Interestingly, a lack of an empathic response was noted as a gap in the neurologists' skills by patients and caregivers (14).

### Strengths and Limitations

To the best of our knowledge our survey is the first addressing the daily practice of consultants in neurology and residents in the Netherlands concerning discussions on treatment restrictions in patients with PD and MS. We found one study in which physicians and bereaved relatives were questioned about decision-making and end-of-life practices in patients with HGG (27).

The overall response rate to our survey was 15%, which is rather low. However, we assume that this still represents a fair proportion of the neurological practices since in most hospitals subspecialized neurologists care for patients with HGG, PD, or MS, respectively. Additionally, the relatively low response rate may be explained by the distribution of the questionnaire via the secretariat of the neurology department for privacy reasons. There are other limitations. First, there may have been "self-selection bias." The majority of respondents had a specialization area so we cannot exclude that consultants in neurology and residents with a special affinity with the topic filled in the questionnaire. Second, due to privacy reasons we do not have information about the non-respondents. Third, we might have influenced the respondents' views. As we aimed to study discussions on treatment restrictions during the whole disease process, we cautiously avoided to use the terms "palliative care" and "end-of-life care" in the questionnaire. Still, it may well be that the phrasing of our questionnaire has triggered certain associations given the responses suggesting that discussing treatment restrictions was closely linked to (starting) end-of-life care. Finally, our data concerning the content of discussions are more representative of HGG than PD and MS due to unequal response rates.

In conclusion, our study suggests that discussions on initiating, withholding, or withdrawing treatment in patients with HGG, PD, and MS are mainly determined by significant cognitive and physical deterioration or the imminent terminal phase. Thus, they usually take place at advanced stages of the disease. The reasons are multilayer and changing daily practice will be a complex challenge. However, education in palliative care skills and knowledge of the overall interest of patients to be involved may be an important step to improve daily clinical practice.

Concrete future research projects arising from our findings should specifically investigate patients' wishes and preferences regarding timing and content of discussions about future care options.

# AUTHOR CONTRIBUTIONS

HAWW contributed in analyzing the data, interpretation of the data, writing, and revising of the manuscript, and accepts responsibility for the corresponding author. AAS contributed to the study design, data collection, interpretation of the data, and writing and revising of the manuscript. DLW contributed to the study design, interpretation of the data, and writing and revising of the manuscript. MdV contributed to the study design, interpretation of the data, and writing and revising of the manuscript. All authors are in agreement with the contents of the manuscript and provide approval for publication of the content.

### REFERENCES

### FUNDING

This study was funded by the Netherlands Organization for Health Research and Development (ZonMw project sj.152.005) which was not involved in any part of the study itself.

### ACKNOWLEDGMENTS

We thank Albert Hijdra for his important role in conceptualizing this study, and Alice Karsten from the Department of General Practice, Amsterdam University Medical Center, location Academic Medical Center, University of Amsterdam, for building the online version of the survey, circulating the survey and collecting respondents' data. We are very grateful for the time the participating consultants in neurology and residents devoted on filling in the survey.

**Conflict of Interest Statement:** The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2019 Walter, Seeber, Willems and de Visser. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Martin Klietz\*† , Amelie Tulke† , Lars H. Müschen, Lejla Paracka, Christoph Schrader, Dirk W. Dressler and Florian Wegner*

*Department of Neurology, Hannover Medical School, Hannover, Germany*

Background: Parkinson's disease (PD) is the second most frequent neurodegenerative disease of the elderly. Patients suffer from various motor and non-motor symptoms leading to reduced health-related quality of life (HRQOL) and an increased mortality. Their loss of autonomy due to dementia, psychosis, depression, motor impairments, falls, and swallowing deficits defines a phase when palliative care interventions might help to sustain or even improve quality of life.

### *Edited by:*

*Giuseppe De Michele, University of Naples Federico II, Italy*

### *Reviewed by:*

*Miguel Coelho, Universidade de Lisboa, Portugal Alessandro Tessitore, Università degli Studi della Campania "Luigi Vanvitelli" Caserta, Italy Silvio Peluso, Azienda Ospedaliera Universitaria Federico II, Italy*

> *\*Correspondence: Martin Klietz*

<EMAIL_ADDRESS>
*† These authors have contributed equally to this work.*

### *Specialty section:*

*This article was submitted to Movement Disorders, a section of the journal Frontiers in Neurology*

*Received: 30 September 2017 Accepted: 19 February 2018 Published: 06 March 2018*

### *Citation:*

*Klietz M, Tulke A, Müschen LH, Paracka L, Schrader C, Dressler DW and Wegner F (2018) Impaired Quality of Life and Need for Palliative Care in a German Cohort of Advanced Parkinson's Disease Patients. Front. Neurol. 9:120. doi: 10.3389/fneur.2018.00120*

Objective: The aim of this study was to investigate the current status of palliative care implementation and quality of life in a local cohort of advanced PD patients in order to frame and improve future care.

Methods: 76 geriatric patients with advanced idiopathic PD meeting the inclusion criteria for palliative care interventions were clinically evaluated by neurological examination using Movement Disorders Society Unified Parkinson's Disease Rating Scale, Barthel Index, Montreal Cognitive Assessment Test, and a structured interview concerning palliative care implementation.

results: HRQOL is severely reduced in our cohort of geriatric advanced PD patients. We found motor deficits, impairment of activities of daily living, depression, and cognitive decline as most relevant factors determining decreased HRQOL. Only 2.6% of our patients reported present implementation of palliative care. By contrast, 72% of the patients indicated an unmet need for palliative care.

conclusion: Quality of life is dramatically affected in advanced PD patients. However, we found palliative care to be implemented extremely rare in their treatment concept. Therefore, geriatric patients suffering from advanced PD should be enrolled for palliative care to provide adequate and holistic treatment which may improve or sustain their quality of life.

Keywords: advanced Parkinson's disease, palliative care, end-of-life care, quality of life, non-motor symptoms

# INTRODUCTION

Parkinson's disease (PD) is the second most frequent neurodegenerative disease of the elderly (1). Despite good treatment options in early disease with fair sustainment of quality of life, in advanced stages of PD therapy can be challenging and quality of life is dramatically reduced (2–4). Additional to motor symptoms such as rigidity, tremor, bradykinesia, and postural instability, patients are affected

**25**

by non-motor symptoms such as depression, obstipation, urinary incontinence, psychiatric disease, and cognitive deficits (5). This symptom burden markedly affects quality of life measured as health-related quality of life (HRQOL) of PD patients and induces caregiver burden as well (6–11). HRQOL and influencing factors are well characterized in early PD, especially dementia is related to poor quality of life and shortened survival (12). Comparatively little is known about determining factors of HRQOL in patients with advanced PD suitable for palliative care interventions (13). Advanced PD patients live with a high symptom burden and an increased risk of mortality, thus, meeting criteria for palliative care. Caregivers of these patients have a high caregiver burden showing a high incidence of depressive symptoms in a small cohort in Germany (caregivers of 20 advanced PD patients) (10).

For advanced PD patients, early implementation of palliative care (e.g., hospice and nursing service, advanced care planning, like feeding in the case of swallowing deficits, airway management, and symptom focused therapy) and end-of-life planning may be the key to adequate treatment and sustainment of quality of life (14). Still, palliative care is offered rarely to these patients (15).  In geriatric patients with advanced PD, drug therapy is often limited by side effects and contraindications due comorbidity. Thus, sufficient symptomatic therapy provided by palliative care concepts can be crucial.

In contrast to the emerging acknowledgment and integration of palliative care in other medical fields, the implementation of palliative care remains uncommon in the treatment of advanced PD in Germany (17). Currently, there are no data available on palliative care implementation in advanced PD treatment and its effects on HRQOL in Germany. Miyasaki et al. report good relief of symptoms in a Canadian study using the Edmonton Symptom Assessment System for PD for palliative care interventions in advanced PD patients (14). Another study reports clinical palliative care interventions for patients with atypical parkinsonisms (18).

To specify the needs of geriatric PD patients in advanced stages of disease, we performed a clinical study investigating HRQOL, its influencing factors, and the extent of palliative care implementation in a local cohort. The aim of this study was to investigate the current status of palliative care implementation in the German health system and to evaluate HRQOL and its influencing factors in this particular group of patients, in order to frame and improve future interventions.

## PATIENTS AND METHODS

We obtained approval from the local Ethics Committee of Hannover Medical School (No. 3123-2016), and patients or their caregivers gave written informed consent. 76 patients with idiopathic PD were recruited from (1) our movement disorder outpatient clinic, (2) our neurological wards, (3) local PD patient support groups, and (4) outpatient neurologists in the region of Hannover, Germany. PD patients who had been admitted *via* the emergency department to our neurological wards were not included in our study until successful treatment had led to a stable condition again. Inclusion criteria for geriatric advanced PD were defined as Hoehn and Yahr stage (H&Y) 3 or more (scored during the on period), 65 years of age or older, disease duration of at least 5 years, and loss of autonomy due to PD (19) because these patients are most likely suitable for palliative care interventions. Patients with atypical parkinsonism and those suffering from much more troublesome comorbidities were excluded from this study.

Participants were examined using MDS-UPDRS (assessment of PD symptoms in the clinical on), MoCA test [cognitive screening test, range from 0 to 30 points, 30–26 points were considered as normal cognitive function, 25–21 points as mild cognitive impairment, and below 21 points as suspicious for dementia (20, 21)], Barthel Index (general performance, activities of daily living), and PDQ-39 (HRQOL specifically constructed and validated for PD). To avoid anosognosia affecting HRQOL measurement, we included demented PD patients only after involvement of the corresponding caregivers who were able to exclude anosognosia as relevant confounder. Furthermore, a structured interview was performed to define the need for and evaluate the frequency of palliative care in these patients. In detail, we evaluated patients' current accommodation and care, such as living at their own home either with or without help by professional caregivers or residing in a nursing home or in a hospice. Participants were asked if they had an advance directive including specific restrictions of therapy and whether they had determined a health-care proxy or someone granted general power of attorney. Patients were interviewed on current implementation of palliative care, such as an outpatient palliative care or hospice service. They also stated if palliative care matters had been addressed by their physicians in the past and whether they had discussed palliative care matters within their family. Finally, they were asked if and with whom—their doctors, family, and friends or others—they wished to discuss palliative care matters and where they would wish to die. Deep brain stimulation, duodopa treatment, and subcutaneous apomorphine therapy as well as oral PD medication was noted for each patient and the equivalence dosage of levodopa was calculated according to Tomlinson et al. (22). A full medical history of all participants was taken, if available, comorbidities and medication were noted from the most updated physician's letter.

Statistical analysis was performed using Graphpad Prism 5.00 (San Diego, CA, USA). Data were analyzed by calculating mean, SD, and range. Comparison between two groups was performed by unpaired Student's *t*-test. Comparison between more than two groups was performed by one-way ANOVA and Newman–Keuls post-test. Correlations were calculated by linear regression analysis (*r*2 = 1 − SSreg/SStot, where SSreg is the variance (sum of squares) of the data of the linear regression model and SStot is the total variance of the *Y* values) and using the sample Pearson correlation coefficient. A *p*-value lower than 0.05 was considered as significant.

### RESULTS

### Quality of Life in Patients with Advanced Parkinson's Disease

In our study, we included 76 patients with advanced PD, 53.9% were female. Our patients presented with a mean H&Y of 4.0 (SD 0.7; range 3–5), and the mean age was 76 years (SD 6.1; range 65–89 years). Mean disease duration was 17.3 years (SD 7.3; range 5–38 years). Participants suffered from severe restrictions in the activities of daily living measured by the Barthel Index (mean 61.8 points; SD 25.4; range 10–100) and by the MDS-UPDRS part II (mean 31.4; SD 8.1; range 16–48).

68 out of 76 PD patients (89.5%) presented with cognitive deficits estimated by a MoCA test score below 26 points and a mean score of 18.4 points (SD 7.8; range 0–30). 50.0% of patients scored below 21 points in the MoCA test which is considered to be highly suggestive for dementia (20, 21). Before study participation, some of our patients (22.4%) had already been diagnosed with dementia according to the S3 guideline for dementia of the German Society of Neurology based on (23). To our surprise, antidementive drugs had been prescribed to only two patients (2.6%). Psychiatric symptoms, measured by the MDS-UPDRS part I item 1.1 "hallucinations and psychosis" (score equal to 2 or more), were reported by 34 patients (44.7%). Almost the same proportion of patients (38.2%) was prescribed neuroleptic drugs (e.g., clozapine or quetiapine).

Depressive mood was present in 52.6% of our patients (40/76) measured by the MDS-UPDRS part I item 1.3 "depressed mood" (score equal to 2 or more). However, a diagnosis of depression in the patients' previous medical documents had been established in only 10.5%, whereas antidepressive medication was prescribed to 15.8% of patients. More extensive and time consuming additional assessments of specific depression and anxiety symptoms could not be performed in this study due to the limited general condition of the patients.

Our patients presented with severe motor impairment determined by the MDS-UPDRS III (60.8 points; SD 16; range 24–96) in the clinical examination. In the MDS-UPDRS part IV, 64.5% of patients reported dyskinesias and 48.7% complained about functional impairments due to dyskinesias. Off-phases were present in 75% of the patients with functional impairment of daily activities. Dystonia in the off-phase was reported by 26.3% of the patients.

The PDQ-39 scale HRQOL was drastically reduced (mean 50.8%; SD 12.4%; range 16.7–75%). Patient characteristics are summarized in **Table 1**.

We found highly significant correlations between HRQOL and the activities of daily living measured by the Barthel Index (*p* < 0.0001; *r* = −0.6946; *r*2 = 0.4825; **Figure 1A**), the MDS-UPDRS part II (*p* < 0.0001; *r* = 0.6586; *r*2 = 0.4338; **Figure 1B**), and motor impairment evaluated by MDS-UPDRS part III (*p* < 0.0001; *r* = 0.4562; *r*2 = 0.2081; **Figure 1C**). MDS-UPDRS part I did not correlate in total score with HRQOL (*p* = 0.12; *r* = 0.2049; *r*2 = 0.0420); however, the items "depressed mood" (*p* < 0.0001; *r* = 0.4862; *r*2 = 0.2364; **Figure 1E**), "hallucinations and psychosis" (*p*= 0.0018; *r*= 0.4841; *r*2= 0.2344; **Figure 1F**), and "anxious mood" (*p* = 0.0431; *r* = 0.2689; *r*2 = 0.0723; **Figure 1G**) correlated significantly with the PDQ-39. HRQOL correlated significantly with cognitive deficits measured by MoCA test (*p* = 0.0002; *r* = −0.4136; *r*2 = 0.1711; **Figure 1D**) and the item "cognitive impairment" of MDS-UPDRS part I (*p* < 0.0001; *r* = −0.5833; *r*2 = 0.3402).

We also correlated the Barthel Index and MoCA scale with the MDS-UPDRS scores to check for co-correlations. Scores from the Barthel Index correlated significantly with MDS-UPDRS part I (*p*< 0.0001; *r*= 0.5177; *r*2= 0.2680), part II (*p*< 0.0001; *r*= 0.7601; *r* = 0.5778) and part III (*p* < 0.0001; *r* = 0.6920; *r*2 = 0.4789), interestingly, they did not correlate with motor complications in the MDS-UPDRS part IV (*p* = 0.9910; *r* = 0.0013; *r*2 < 0.0001). Concerning the MoCA score of the patients we found significant correlations with the MDS UPDRS part I (*p*< 0.0001; *r*=−0.4843; *r*2 = 0.2345), part II (*p* < 0.0001; *r* = −0.5160; *r*2 = 0.2663) and

*H&Y, Hoehn and Yahr stage; MDS-UPDRS, Movement Disorders Society Unified Parkinson's Disease Rating Scale part I-IV; MoCA, Montreal Cognitive Assessment test; PDQ-39, Parkinson's Disease Quality of life form 39; LED, calculated l-DOPA equivalence dosage.*

Figure 1 | Significant correlations of health-related quality of life (HRQOL) with different scales und symptoms. (A) Negative correlation of HRQOL and Barthel Index (*p* < 0.0001; *r* = −0.6946; *r* 2 = 0.4825). (B) Correlation of HRQOL with Movement Disorders Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part II (*p* < 0.0001; *r* = 0.6586; *r* 2 = 0.4338) and (C) MDS-UPDRS part III (*p* < 0.0001; *r* = 0.4562; *r* 2 = 0.2081). (D) Negative correlation of HRQOL and Montreal Cognitive Assessment test (MoCA) (*p* = 0.0002; *r* = −0.4136; *r* 2 = 0.1711). (E) Correlations of HRQOL with MDS-UPDRS part I item "depressed mood" (*p* < 0.0001; *r* = 0.4862; *r* 2 = 0.2364) and (F) MDS-UPDRS part I item hallucinations and psychosis (*p* = 0.0018; *r* = 0.4841; *r* 2 = 0.2344) and (G) MDS-UPDRS item "anxious mood" (*p* = 0.0431; *r* = 0.2689; *r* 2 = 0.0723). (H) Non-significant correlation of HRQOL and levodopa equivalence dosage (LED) (*p* = 0.5035; *r* = 0.0825; *r* 2 = 0.0068).

III (*p* < 0.0001; *r* = −0.7163; *r*2 = 0.5131) but not with part IV (*p* = 0.2849; *r* = −0.1241; *r*2 = 0.0154). Additionally, we found a significant correlation of MoCA scores and the MDS-UPDRS part I items "anxious mood" (*p*= 0.0063; *r*=−0.3108; *r*2= 0.0966) and "hallucinations and psychosis" (*p* = 0.0011; *r* = −0.3667; *r*2 = 0.1345).

Regarding motor complications measured by the MDS-UPDRS part IV and their impact on HRQOL, we found no correlation of dyskinesias and HRQOL (MDS-UPDRS IV item 1, *p* = 0.9342; *r* = 0.0096; *r*2 < 0.0001 and 2, *p* = 0.3794; *r* = 0.1029; *r*2 = 0.0106). The frequency of off-time correlated significantly with HRQOL (*p* = 0.0339; *r* = 0.2454; *r*2 = 0.0602); however, the functional impairment of off-time (item 4, *p* = 0.1267; *r* = 0.1779; *r*2 = 0.0316) and the complexity of off-phases (MDS-UPDRS IV item 5, *p* = 0.1480; *r* = 0.1686; *r*2 = 0.0284) did not correlate with HRQOL. Off-dystonia correlated significantly with HRQOL (*p* = 0.0490; *r* = 0.2280; *r*2 = 0.0520).

Treatment regimens markedly differed between individual patients. The number of prescribed PD drugs ranged from one to six groups of medication [levodopa + decarboxylase inhibitor; dopamine agonist; MAOB inhibitor (14.5%); safinamide (8.7%); amantadine (17.6%); COMT inhibitor (40.1%)]. The vast majority received levodopa therapy (98.5%). More than one-third was treated with additional dopamine agonists (41.2%). Interestingly, the calculated equivalence dosage of levodopa did not correlate with HRQOL at all (*p* = 0.5035; *r* = 0.0825; *r*2 = 0.0068; **Figure 1H**). We included 14 patients with DBS (18.4%), 9 patients with duodopa intrajejunal therapy (11.8%) and 3 patients with apomorphine subcutaneous pump (3.9%). No significant differences in HRQOL and motor impairment were found in patients with DBS or duodopa therapy compared to each other and to the cohort with oral medication only (*p*> 0.05, one-way ANOVA and Newman–Keuls post-test). Due to the low number of patients, we did not calculate any data for the apomorphine group.

In the medical documents of our PD patients, we screened for systemic diseases. Note, we excluded patients predominantly suffering from another severe disease than PD. We found 30.3% of patients to be diagnosed with arterial hypertension. Cardiovascular disease, excluding arterial hypertension, was present in 27.6% of the cohort. Diabetes type 1 or 2 was diagnosed in 7.9%; other endocrine diseases, such as hypothyreosis, were present in 13.2% of the patients.

# Palliative Care in Advanced Parkinson's Disease

Approximately half of our patients managed to schedule regular appointments with an outpatient neurologist. Most neurological consultations of the other patients had to be done *via* the emergency department.

We found 70% of our patients to have an advance directive and a health-care proxy. However, hardly any patient was provided with additional palliative care at their home or had ever consulted their treating physicians on palliative care matters (**Table 2**). Overall, we found palliative care to be provided to only 2 out of 76 severely diseased PD patients (2.6%). 72% of the patients expressed an unmet need for information concerning palliative care, especially about advance care planning concerning endof-life care (EoLC). In more than 40% of the patients, there had been no discussion about EoLC in the family. Almost half of the patients preferred to consult with their general physician or outpatient neurologist about palliative care matters (**Figure 2**). The majority of patients wishes to die at home. However, it remains challenging to simultaneously receive professional palliative and neurological care guaranteeing fair symptom control in order to honor this wish in dignity (**Figure 2**).

### DISCUSSION

By applying the following inclusion criteria, we defined a palliative care intervention phase of advanced PD according to Saleem et al. (15): H&Y 3 or more, 65 years of age or older, disease duration of at least 5 years, and loss of autonomy due to PD. Patients' parameters such as treatment plans and equivalence dosage of levodopa were in line with earlier reports of long-term surviving PD cohorts from Australia (24) and the US (13). However, patients recruited in our study were older (75.5 years) compared to the Sidney cohort (71 years) (24) and the US cohort (69.5 years) (13). Our patients presented with a higher mean H&Y and a mean disease duration of 17 years, which was 2 years longer than in the study of Hely et al. from 2005 (24). We specifically aimed to measure a geriatric population and, thus, set the inclusion criteria for age at 65 years or older to recruit a more homogeneous group as PD patients seem to reach the palliative care intervention phase of PD in the age of 65 and older (25).

Cognitive deficits were prominent in all comparable cohorts and were impacting HRQOL, nevertheless the prevalence of cognitive deficits and dementia measured by the MoCA Test was dramatically increased in our group of patients compared to the other cohorts. Hely et al. (24) found 48% of the long time PD patients to be demented, measured by the Mini-Mental State Test, whereas Hassan et al. (13) reported a mean MoCA score of 22.6 in their cohort. In our cohort, the MoCA score was markedly lower with a mean value of 18.4 points. We measured HRQOL with the well-established and validated PDQ-39 form (26). In all comparable cohorts, quality of life is decreased significantly and the reduction is related to the duration of disease (2, 13, 24, 27). Hassan et al. (13) described

Table 2 | Palliative care implementation in geriatric advanced Parkinson's disease patients (*n* = 76).

Klietz et al. Palliative Care in Advanced PD

a decrease of 35.8% in quality of life measured in the PDQ-39, which was less prominent than in our cohort (50.8% and SD 12.4%). Considering the higher mean age, comparably long disease duration and extraordinary high prevalence of cognitive decline, it seems likely for our patients to have markedly decreased HRQOL. In our collective of advanced PD patients, we identified motor symptoms, cognitive decline, depression, hallucinations, anxiety, and impairment in the activities of daily living as main factors significantly correlating with decreased HRQOL. In accordance to other studies motor symptoms, cognitive deficits, depression, and psychiatric symptoms showed the strongest correlation with decreased HRQOL (2, 3, 6, 11, 12, 27). In regard to motor complications of advanced PD patients, the most dominant factor in our study appears to be the amount of off-time per day. We also found off-dystonia to negatively impact HRQOL. Interestingly, dyskinesias did not show a significant correlation with HRQOL in our study. It seems that dyskinesias did not or only mildly impact HRQOL in advanced PD (28–30). Therefore, treatment of motor complications should specially aim to reduce off-time of PD patients in advanced stages.

Former studies in advanced PD did not investigate possible benefits of invasive therapies such as DBS or duodopa pump therapy in a palliative setting, which is why we compared HRQOL in patients receiving DBS or duodopa to patients treated with oral medication only. Despite a previously reported positive effect on quality of life of DBS (31) and duodopa treatment (32) for individual patients, we were not able to show a higher HRQOL in our small DBS and duodopa groups compared to patients receiving oral PD medication only.

By considering comorbidities of advanced PD patients, we found cardiovascular disease and hypertension to be the most frequent systemic diseases in their medical history. Generally, PD patients suffer less often from cardiovascular disease and hypertension (33). PD patients may have a special cardiovascular profile of comorbidities compared to the general population possibly caused by peripheral autonomic disturbances. In the context of palliative care, it is important to notice that the cause of death in PD patients is pneumonia to a huge proportion (34), whereas the frequency of cardiovascular and cerebrovascular causes of death is reduced to values of control populations (33, 35, 36). Therefore, we would expect only a limited effect of cardiovascular disease and hypertension on the HRQOL of our PD cohort.

As shown in our data and by others, HRQOL is dramatically decreased in the palliative intervention phase of PD (13, 24). Palliative care may help to sustain or even improve quality of life in these patients by targeting specific symptoms, especially those determining poor HRQOL (14, 17). Only 2 of our 76 patients received palliative care at all, which is in line with observations of Saleem et al. (15) who also found rare implementation of palliative care in advanced PD patients in the UK. Reason for that might be a lack of awareness of clinical criteria when and how to initiate palliative care in PD (19, 37). In our study, a high number of patients reported the wish to die at home, which is in accordance with previous publications (16, 38). However, neurologists and general physicians may not be fully aware of the increased mortality of PD patients and consequently fail to duly address advance care planning during their consultations (39). It is necessary to encourage patients and their caregivers to discuss EoLC and note life-sustaining treatment orders for

and discharge to a hospice. Even in the palliative intervention phase, the end-of-life care (EoLC) represents only a small proportion of palliative therapies.

better care planning according to their individual wishes (40, 41). In regard to the high prevalence of cognitive decline in our cohort, an early advance care planning is of fundamental importance. Additionally, health care by proxy should be discussed in early course of the disease. In later disease stages, decision-making related to goal of care could be compromised by cognitive impairments (42). For excellent reports of advance directives in patients with dementia in the context of ethical and law issues, see Ref. (43, 44). Clearly, defined clinical criteria indicating a time point for palliative care implementation might help to improve future treatment for advanced PD patients. Richfield et al. have defined possible mile stones for initiation of EoLC such as swallowing problems, recurrent infections, marked decline in physical function, first aspiration pneumonia, cognitive difficulties, weight loss, and significant complex symptoms (37, 45). With occurrence of these symptoms, palliative care interventions are helpful and initiation of EoLC should be evaluated.

Especially in Germany, we are just at the beginning of properly providing palliative care for neurological patients in general. To serve that purpose, it seems constructive to form interdisciplinary teams (e.g., neurologist, palliative care specialist, PD nurse, and social worker) following the model of Miyasaki et al. in Canada (14). Thereby, the awareness of neurologists concerning palliative care in advanced PD could be improved. Considering our data and recent literature (15, 16), we suggest the following model for palliative care in PD (**Figure 3**).

Possible limitations of our study are the monocentric approach with a moderately high number of patients (*n* = 76) as well as the restrictive inclusion criteria defining a severely burdened subgroup of PD patients. Due to the evaluation of numerous patient characteristics and extensive neurological examination, it did not seem feasible to apply additional and more specific questionnaires for depression and anxiety. However, for a general

## REFERENCES

and fast assessment of anxiety and depression, the items of the MDS-UPDRS part I can be used in clinical practice (46). We plan the detailed investigation of this issue in a future study explicitly focusing on depression and anxiety symptoms based on our recent results.

In our study, we found that palliative care is not yet a fixed component of PD treatment which is in line with general observations in German PD patients, although implementation of palliative care in advanced PD can be crucial and is often called for. This characterization of severely diseased PD patients contributes novel clinical data and forms the basis for further trials aiming to improve palliative care implementation in advanced PD patients in order to establish optimal symptom control, sustain quality of life, reduce caregiver burden, and prevent caregiver burnout (10). Our data emphasize the urgent need of palliative care in geriatric advanced PD patients.

# ETHICS STATEMENT

We obtained approval from the local Ethics Committee of Hannover Medical School (No. 3123-2016), and patients or their caregivers gave written informed consent.

## AUTHOR CONTRIBUTIONS

MK and FW planed the study. AT, MK, LM, LP, and DD recruited the patients. MK, AT, LP, and FW analyzed the data. MK, AT, LM, LP, CS, DD, and FW wrote and corrected the manuscript.

# ACKNOWLEDGMENTS

This study was supported by a Grant of Hilde-Ulrichs foundation Frankfurt am Main, Germany, to MK. The authors thank N. Ziegler, L. Diekstall, and H. Gorzolla for excellent assistance.

dopaminergic therapy: how do they correlate with quality of life? *ISRN Neurol* (2014) 2014:1–4. doi:10.1155/2014/587302

scale, the ESAS-PD. *Parkinsonism Relat Disord* (2012) 18:S6–9. doi:10.1016/j. parkreldis.2012.06.013

**Conflict of Interest Statement:** The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The reviewer SP and handling Editor declared their shared affiliation.

*Copyright © 2018 Klietz, Tulke, Müschen, Paracka, Schrader, Dressler and Wegner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.*

# Alleviation of Psychological Distress and the improvement of Quality of Life in Patients With Amyotrophic Lateral sclerosis: Adaptation of a short-term Psychotherapeutic intervention

### *Moritz Caspar Franz Oberstadt1 \*, Peter Esser 2 , Joseph Classen1 and Anja Mehnert 2*

*1Department of Neurology, University Medical Center Leipzig, Leipzig, Germany, 2Department of Medical Psychology and Medical Sociology, University Medical Center Leipzig, Leipzig, Germany*

### *Edited by:*

*Raymond Voltz, Uniklinik Köln, Germany*

### *Reviewed by:*

*Elizabeth Ann Mauricio, Mayo Clinic, United States Fiore Manganelli, Azienda Ospedaliera Universitaria Federico II, Italy*

### *\*Correspondence:*

*Moritz Caspar Franz Oberstadt<EMAIL_ADDRESS>
### *Specialty section:*

*This article was submitted to Neuromuscular Diseases, a section of the journal Frontiers in Neurology*

*Received: 17 January 2018 Accepted: 26 March 2018 Published: 16 April 2018*

### *Citation:*

*Oberstadt MCF, Esser P, Classen J and Mehnert A (2018) Alleviation of Psychological Distress and the Improvement of Quality of Life in Patients With Amyotrophic Lateral Sclerosis: Adaptation of a Short-Term Psychotherapeutic Intervention. Front. Neurol. 9:231. doi: 10.3389/fneur.2018.00231*

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that is inevitably fatal. To be diagnosed with a terminal illness such as ALS deeply affects one's personal existence and goes along with significant changes regarding the physical, emotional, and social domains of the patients' life. ALS patients have to face a rapidly debilitating physical decline which restrains mobility and impairs all activities of daily living. This progressive loss of autonomy may lead to a sense of hopelessness and loss of quality of life, which in turn may even result in thoughts about physician-assisted suicide. Here, we would like to propose a psychotherapeutic manualized, individual, semi-structured intervention to relieve distress and promote psychological well-being in ALS patients. This short-term intervention was originally developed for advanced cancer patients. "Managing Cancer and Living Meaningfully (CALM)" focuses on the four dimensions: (i) symptom management and communication with healthcare providers, (ii) changes in self and relations with close others, (iii) spirituality, sense of meaning and purpose and (iv) thinking of the future, hope, and mortality. We suggest to supplement the concept by two additional dimensions which take into account specific issues of ALS patients: (v) communication skills, and (vi) emotional expression and control. This therapeutic concept named "*M*anag*I*ng *B*urden in *A*LS and *L*iving *M*eaningfully (mi-BALM)" may be a further treatment option to help improving quality of life of ALS patients.

Keywords: amyotrophic lateral sclerosis, psychotherapeutic intervention, calm, quality of life, distress

# AMYOTROPHIC LATERAL SCLEROSIS (ALS)

Amyotrophic lateral sclerosis represents a rapidly progressing neurodegenerative disease and is characterized by a degeneration of motor neurons (1). ALS affects the upper motor neurons projecting from the cortex to the brainstem and the spinal cord as well as the lower motor neurons projecting from the brainstem or spinal cord to the muscles (1). The initial presentation of ALS varies considerably between patients: while some patients first experience muscle weakness in the limbs, referred to as spinal onset, others initially suffer from dysarthria and dysphagia, characterized as bulbar onset. Bulbar onset appears in about one-third of patients with ALS and is often associated with emotional lability, which may arise from disconnection of brainstem structures from cortical inhibition (2, 3). Limb-onset weakness accounts for 60% of cases, presents usually asymmetrically and may first develop in either the upper or lower limbs. Apart from weakness, additional symptoms may include spasticity as a sign for upper motor neuron loss, and fasciculations, cramps and muscle atrophy as signs for lower motor neuron loss. Death usually results from respiratory failure which is caused by the loss of nerve supply of the respiratory muscles (3). The average life expectancy of patients with ALS is 2–3 years from the onset of symptoms, while a minority (4%) survive for 10 years or even longer (4, 5). The incidence of ALS is about two cases per 100,000 individuals and the age of onset peaks at 70–74 years (6).

In most cases, ALS appears to develop sporadically, although some patients have a familial disease which is associated with mutations in genes that have a wide range of functions (3). The primary symptoms of ALS are associated with motor dysfunction, such as muscle weakness or dysphagia, but more than 40% of ALS patients additionally develop cognitive or behavioral symptoms in advanced stage of the disease and about 14% of patients present with accompanying frontotemporal dementia (7).

# MENTAL BURDEN AND CHALLENGES IN THE PROGRESSION OF THE DISEASE

To be diagnosed with a life-threatening illness, such as ALS, deeply affects one's personal existence and involves a variety of changes in the physical, emotional, and mental-cognitive aspects of a patients' life. At first, ALS patients realize the debilitating physical symptoms due to muscle weakness impairing mobility and autonomy in all activities of daily living (8). A characteristic of ALS is the impairment to communicate verbally due to dysarthria, which means a motor disorder of speech characterized by abnormalities of the articulation and reduced intelligibility of speech. Dysarthria appears in 25–30% of ALS patients as a first or predominant sign in early stage (9) and the potential loss of speech has been rated as one of the three worst aspects of the disease by ALS patients (10). Furthermore, patients suffer from numerous symptoms, including pain, spasticity, difficulty in swallowing, weight loss, and respiratory insufficiency that require intensive treatment by a multidisciplinary care team (11). Among the wide range of symptoms, pain seems to be particularly frequent and to play a major role in affecting the quality of life in ALS patients (12, 13). Moreover, progressive muscle weakness leads to dependence on others like familial caregivers and/or a multiprofessional care team because of immobility (8). Patients have to face mental-cognitive challenges, to adapt to the new life situation and to decide about permanent and invasive medical measures including gastrostomy tube placement and assisted ventilation during disease progress (14). With the respect to the progredient loss of the ability to speak, patients and their related persons have to find new ways of communication, such as computer-based communication devices, such as eyetracking systems (15). Progressive loss of autonomy and control may lead to severe emotional reactions, including of help- and hopelessness and a complete loss of motivation (16). Regarding potential risk factors for emotional impairments caused by the disease, hopelessness in ALS patients is predicted by the belief that life is determined by forces beyond his or her own control (external locus of control) and a lack of meaning of life, but not by socioeconomic or demographic factors, length or severity of illness, social support satisfaction or spiritual belief (17). Just as hopelessness, depressive symptoms are not related to time since diagnosis, the degree of disability or the progression of the illness (18), but slightly increase with speed of disease progression (19). Depression scores vary considerably between studies and range from 35 to 57% (20–24). Compared to other somatic patient groups including patients with cancer or heart failure, ALS patients most frequently ask for physician-assisted suicide (25, 26). Emotion in ALS patients may be difficult to recognize because emotional expression is frequently altered by the disease. Up to 49% of ALS patients show uncontrollable outbursts of laughter or crying without any appropriate environmental trigger and may be either more pronounced or even incongruent with the underlying emotional state (27, 28). This emotional expression disorder is named "pseudobulbar affect" and poses a problem in correct recognition and interpretation of emotional signs, not only for related persons, but also in therapeutic settings (29).

Taken together, previous research indicates a broad spectrum of physical, emotional, and mental-cognitive challenges for ALS patients (**Table 1**), which all have to be addressed by a multimodal (psycho-)therapy.

## FUNDAMENTALS OF PSYCHOLOGICAL INTERVENTIONS IN PALLIATIVE CARE

The high prevalence of mental burden like anxiety and depression, including hopelessness, despair, and demoralization in palliative patients demonstrate the need for effective psychological interventions integrated in palliative care concepts (30). Psychological

Table 1 | Specific aspects of amyotrophic lateral sclerosis (ALS) for (psycho-) therapeutic settings.

interventions can address a wide spectrum of objectives in palliative care and together aim to reduce psychosocial distress and maintain quality of life in patients and their caregivers (31). These interventions intend to help the patient and family in coping with the fear of death and dying, managing anxiety, and reducing feelings of isolation, sadness, despair, and depression (32). Other psychological approaches address problems associated with changes of social roles and relationships, increasing dependence on others, the need to adjust to impaired functional status, and existential concerns, such as the search for meaning in life, hope, sense of dignity, grief, and spirituality (32). Clinical psychotherapeutic care for patients with progressing diseases comprises a variety of interventions and techniques, all of which have to be integrated into a multidisciplinary care plan. These include cognitive behavioral therapy, psychodynamic therapy, narrative interventions, relaxation and guided imagery, mindfulness-based interventions, meaning-focused interventions, art therapy, and dignity therapy (33).

# Psychotherapeutic Topics and Psychological Needs in Palliative Settings

The "psychotherapeutic work and goals in palliative care settings generally differ in several aspects from psychological interventions for patients with early or curative diseases or physically healthy individuals" (32).

In palliative settings, psychotherapeutic support starts with the diagnosis of the incurable disease. After communication of the diagnosis, patients often need time for reflection and room in which they can express their emotions. Because the delivery and communication of the diagnosis and its consequences is a crucial and emotionally relevant moment for the patient and his/ her relatives, a psychologist in the medical team provides the patients with an additional opportunity to express their feelings and fears (34).

Furthermore, the time frame for psychotherapeutic interventions may be limited, especially in the case of ALS patients. Usually, "patients can be see" by the psychotherapist "only a few times, depending on their physical condition, the course of the disease," and the setting (inpatient vs. outpatient). "The limited time has several implications for the development of a trustful and sustainable therapeutic relationship and psychotherapeutic treatment planning" (32). Treatment planning often depends on the stage and course of the disease and always has to be flexible enough to take into account spontaneous changes in the supportive care needs of patients or their caregivers. These and rapid changes in the course of the disease may place high demands on the clinical psychologist with regards to flexibility, empathy, and understanding of the patient's situation (32).

"Treatment planning for patients with serious illnesses must also consider that communication with the patient and caregiver can be hampered by severe health conditions" (32). In ALS patients, poor articulation or even the inability to speak, and, in some cases, cognitive impairment and behavioral changes may significantly affect communication (35).

In addition, communication with the patient and caregiver can be compromised by unclear or divergent perceptions and prognostic awareness about the goals of treatment and the curability of the disease. Prognostic awareness contains multifactorial components, such as awareness of (i) the terminal nature of one's illness, (ii) the purpose of treatment, or (iii) a shortened life expectancy (36). Palliative care patients show a wide range of prognostic awareness, reaching from 0 to 75% (37).

There are multiple reasons why patients report limited or inaccurate prognostic awareness including the lack of information given by physicians, such as incomplete understanding of the information, intentional or unintentional denial to accept the prognosis, and the phenomenon of "double awareness": mixed states of awareness, hope for cure or hope for longer survival, despair or (partly) denial (36, 37).

Having this phenomenon of *double awareness* in mind, "the clinical psychologist is often faced with the difficult task of encouraging patients and caregivers to cope adaptively while promoting acceptance" (32). "Support for coping may focus on maintaining hope and quality of life, and reducing psychological stress. Acceptance may require that patients and caregivers face realistic treatment goals and treatment decisions, which themselves may negatively affect the psychosocial well-being of the patient and the family" caregivers. "The psychologist must be prepared to manage the emotional responses of the patient and the caregiver" and, finally, "clinical psychologists working in palliative care settings must be prepared to deal with" their own emotional reactions caused "by the closeness to death and dying," helplessness, and existential or spiritual questions about the meaning of life and death (32).

# INTRODUCTION OF THE PSYCHOTHERAPEUTIC SHORT-TERM INTERVENTION BASED ON CALM IN ALS PATIENTS