NeuroPalliative Care

Dr. J. Miyasaki, MD, MEd, FRCPC

Professor, Director Parkinson and Movement Disorders Program, Co-Director, the

Complex Neurologic Symptoms Clinic

Division of Neurology, University of Alberta

Faculty/Presenter Disclosure

• Faculty: Janis Miyasaki

• Relationships with financial sponsors:

- Grants/Research support: Allergan; Patient Centered Outcome Research Institute

-Speakers Bureau/Honoraria: N/A

- Consulting Fees: GE

- Patents: N/A

- Other: UptoDate: Royalty for book

1. Prevalence, natural history, pathophysiology, end of

life trajectory, symptoms relevant to palliative care,

treatments of the symptoms of:

2. Severe Acute Brain Injury, PD and related disorders

and dementia, MS, ALS

3. In 45 minutes with mandatory 15 minutes of

interaction

Objectives

Theoretical Trajectories of Dying

2Lunney, JR et al. Patterns of Functional Decline at End of Life. JAMA, 289(18): 2387-2392.

Opportunities for Palliative Care

Approach

Ho

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Dia

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Level of

Function

Time

Illnesses have Motor and Non-motor symptoms

Undetected pain is often reason behind MAID requests

Cognitive decline occurs in many illnesses thought of as

purely motor

Find a motivated neurologist in an academic setting to

partner with you

Consider attending clinics with advanced illness patients

to learn common scenarios and treatment tips

Overarching Theme of Neurologic Illness and

Palliation

Typical neuroleptics

Atypical neuroleptics – except quetiapine or clozapine

Metoclopramide, nozinan

Nearly all neurologic patients will have dementia at the

end of life – therefore, delirium may not be avoidable if

good pain control is also required

Medications to Avoid with Neurologic Patients

Ischemic stroke

Intracerebral or subarachnoid hemorrhage

Traumatic brain injury

Inflammatory brain injury

Severe Acute Brain Injury

1%/year in Canada

Third most common cause of mortality (after heart attack

and all cancers combined)

Risk factors: hypercholesterolemia

Diabetes

Smoking

Cocaine, heroine, methamphetamine

Stroke Prevalence

Behavioral Pain Scale

Common Symptoms after SABI

Paroxysmal sympathetic hyperactivitiy

Hyperthermia

Hypertension

Tachycardia, tachypnea

Increased muscle tone

Diaphoresis

Storming

Symptoms after SABI

Triggers for Conversations about Goals

Triggers for Conversations

Inability to maintain hydration and caloric intake + One

of:

Palliative Performance Scale < 40%

Weight loss >10%/6mo or >7.5%/3mo

Serum albumin low

Dysphagia severe enough to prevent receiving sufficient

food and fluid to sustain life and patient does not receive

artificial nutrition and hydration

Consider LTC and Community Pall or Inpatient

Palliative Care if:

275-500/100,000 prevalence

Average age of onset 55 years

Mean survival: 15 years

Pathophysiology: progressive neurodegenerative

disorder with unknown etiology

Parkinson disease

Parkinson’s disease – “slow” progression

Lewy body dementia – cognitive change precedes or

within 1 y of motor, cognitive fluctuations, hallucinations

Multiple system atrophy- dysautonomia + parkinsonism

or ataxia

Synucleinopathies

With permission from Lang and

Lozano, NEJM, 1998

What predicts mortality in Parkinson’s disease

Neurology 2010;75:1270

Williams,

Neurology

2006

Cause of Death Over 10 y

Williams-Gray JNNP 2013

Bothersome or disabling pain not responsive to PD

medication management

Behavioural complications requiring reduced motor

control

Caregiver distress or burnout

Recent or repeated hospitalizations

Loss of ability to drive

Falls or need for gait assistance

Cognitive impairment

Potential Triggers for Palliative Conversations

Behavioural issues: hallucinations, delusions, wandering

Significant dysphagia

Hospitalization from aspiration pneumonia

Weight loss

Existential distress

Acceleration in changes in functional status

Triggers

Rotigotine 3 mg (patch) = 100 mg Levodopa

Beware confusion, somnolence, psychosis

Rectal Levodopa:

Crush 10 tabs 100/25

Add to 10 ml 50% H2O, 50% glycerol + 1 g citric acid

100 ml/ml

Shake well before use

Unable to Swallow

Rotigitine patch (beware psychosis/confusion, orthostatic

hypotension)

Rectal levodopa

Give regular levodopa by PEG if in place – be aware

duration of action will be approx. 30-60 min/dose

Alternatives to Oral Levodopa

Outcomes

ESAS-PD improved significantly (56 to 40)and to similar

extent as those with endstage metastatic cancer (48 to 39)

p <0.0001 (95% CI 10,21)

Symptoms responding most to interventions: Dysphagia,

constipation, anxiety, pain, drowsiness and other

Zarit Caregiver Burden Scale (modified) improved from

mean V1 43.5 to V2 36 (p < 0.0001, 95% CI 6, 9) (max

score 96)

Cause of death in clinic

130 patients: 33 deaths

Place of death: LTC 4

Home 29 (community palliative care)

Palliative inpt unit 4

Acute care hospital 6 (no hospice bed 1)

Cause of death: aspiration pneumonia 26

died in sleep 5

other 2

NO metoclopramide, nozinan, any typical or atypical

neuroleptic

EXCEPT quetiapine and clozapine

Do NOT stop Parkinson medications unless imminently

dying

Practical Tips

Prevalence: 10-20/100,000

Life expectancy: 5 years (range 2 years-20)

Pathophysiology: synucleinopathy

Many symptoms overlap with PD, but compressed in time

course – always changing, relentless, more pain

Multiple System Atrophy

Jnnp Glasmacher, Leigh, Saha

What predicts mortality in MSA

Edmonton Symptom Assessment

System:MSA

0

2

4

6

8

10

12

Pain Tiredness Drowsiness Nausea Appetite SOB Depression Anxiety Wellbeing

MSA: Other Important Symptoms

Confusion

What predicts mortality in Progressive

Supranuclear Palsy?

Alzheimer disease: 4.4% of the population 65+

19/1000 population

Vascular dementia: 26% of all dementias

Prevalence 0.6-2% of those over 65 y

What specific dementia diagnoses do you know?

AD accounts for 60-80% of all cases

Amnestic – short then immediate, last remote

Socially appropriate

Vascular dementia 10-28%

Stepwise progression

Lewy body dementia 5-20%

Cognitive fluctuations, hallucinations, dysautonomia

Exactly like Park dis dementia except within 1 y of motor

symptoms

Dementia

5-10%

Onset 45-64 (younger than AD)

Executive dysfunction: poor decision-making, lack of

empathy, impulsiveness

Can occur with ALS

May be inherited as autosomal dominant

Frontotemporal Dementia

From Neuropalliative Care, 2018

Functional Assessment Staging

At FAST 7 25% 6 month mortality, median survival 1.3 years

Steps for Dementia Palliation

Stage/Trigger Palliative Care Interventions

Time of Dx

New behavioural symptoms

GOC

PD, POA

Rx depression, cognitive symptoms

Caregiver support

Moderate: new or inc agitation

Inc dependency

Screen and treat Psychiatric Sx

Safety screening: finances, driving,

abuse

Caregiver support

Assess care needs

Severe: incontinence

Dec ambulation, frequent falls

Dec ability to have a conversation

Choking dysphagia

Pneumonia, Weight loss,

Hospitalizations

Symptom management

GOC reassessment

De-prescribe medications of limited

benefit

Consider hospice or LTC referral

Pain Assessment in Advanced Dementia (PAINAD)

Observation 0 1 2

Breathing Normal Occ laboured

breathing, short

hyperventilation

Noisy laboured,

longer period of

hypervent or CS

Negative

Vocalization

None Occ moan/groan

Low level neg

Repeated calling

out, loud moaning,

groaning, crying

Facial Expression Smiling or

inexpressive

Sad, Frightened,

Frown

Grimacing

Body Language Relaxed Tense, distressed

pacing, fidgeting

Rigid, fisting,

pulled up, striking

Consolability No need to

console

Distressed or

reassured by

voice or touch

Unable to console,

distract

Warden, 2003

Screen for hunger, thirst, need to urinate,

defecate/constipation, inability to communicate

Strained staff/caregiver

Past history of physical or sexual trauma may make even

good nursing care traumatic

Unmet Physical or Emotional Needs

Leading cause of institutionalization and death in older

population

Severe functional limitation occurs

Explore GOC early while patients still capable

Behavioural management is challenging

Practice Tips

290/100,000

Highest in Edmonton

Relapsing Remitting – means recovery after attacks

Primary Progressive – progressive decline after

diagnosis, may have acute relapses but less recovery

Secondary Progressive: start as relapsing remitting and

then become progressive

Related: Acute Disseminated EncephaloMyelitis

Multiple Sclerosis

Multiple disease modifying therapies mean patients receive

intensive therapy

Degree of immunosuppression correlates with risk of

Progressive Multifocal Leukoencephalopathy

Congestive Heart Failure

Pulmonary Fibrosis

Cognitive decline varies with disease burden

MS: Challenges based on Age and Previous

Treatments

Disability is assessed by the Expanded Disability Status

Scale – heavily weighted by mobility

0: asymptomatic

1-3 moderate but ambulatory independently

6 wheelchair

9 bedridden 10 dead

MS: The Challenge of Advanced Disability

Fatigue

Cognitive changes

Communication/Dysphagia

Spasticity

Tremor

Social Isolation

Marital breakdown

MS Advanced Symptoms

Early: Time of diagnosis

Acute Demyelinating Encephalomyelopathy or Neuromyelitis

Optica

First presentation requiring ICU stay

Potential Triggers for Palliative Care

Having to change or stop work

Loss of ability to drive

Chronic pain

Marital breakdown, loss of caregiver support

Wheelchair required

Urinary incontinence or catheterization required

Cognitive changes

Advanced Disease Triggers

Advancing cognitive dysfunction and dementia

Admission to long term care

De-prescribing immune modulating treatments

Dysphagia, risk of aspiration and reduced nutritional

intake

Recurrent infections/hospitalizations

Later Stage Disease Triggers

Up to 80% of patients

Spasticity

Spasm (hemifacial spasm, trigeminal neuralgia or

other)

Neuropathic pain

Skin or pressure ulcers

Pain

Physiotherapy

Baclofen 10-40 mg tid: unsteadiness, excessive

weakness, confusion

Gabapentin (?), dantrolene

Botulinum toxin

Cannabis: Delirium

Spasticity

Avoid overheating

Amantadine: anticholinergic effects 100-200 mg bid

Methylphenidate

Modafanil

Fatigue

Occupational therapy

Weights on wrist

Typically refractory to treatment

NO effective medications

DBS occasionally successful – may precipitate attack

Tremor

Awareness that cough may not be present

Careful hand feeding

PEG has not been assessed but can be useful

If drooling is disabling, consider

Atropine patch (cut in ½ or ¼)

Glycopyrolate

Botulinum toxin injections: worsen dysphagia

Dysphagia

May have any combination of problems

Overactive: spastic bladder, oxybutynin, catheterization

Detrusor sphincter dyssynergia: botulinum toxin

injection, bethanechol, catheterization

Retention: catheterization

Consider urodynamics

Bladder Dysfunction

Up to 60%

Higher risk if limbic involvement, during relapses

NOT related to duration of illness

Suicidality 4 x population controls

monitor patients treated for depression

Requests for MAID 4 x population controls in Belgium

Depression and Suicidality

Incidence 2/100,000/y

Age of Onset: 55-70 y

Mean survival: 3-5 y

Motor: fasciculations, cramps, weakness, muscle wasting

Bulbar onset: facial weakness, dysphagia, dysarthria,

respiratory failure and inability to wean from ventilator

Cognitive: Frontotemporal dementia 45-55%,

pseudobulbar affect

Amyotrophic Lateral Sclerosis

Better accuracy if patient is followed over time

Faster progression if: Age >75

Bulbar onset

BMI < 25

ALS Functional Rating Scale: 25% decline in functional

status

Prognostication

ALS Functional Rating Scale

4 3 2 1 0

Speech Normal Abn Repeat Speech combined w

nonvocal

communication

none

Salivation None Slight Moderate Marked excess Drooling

Swallow Normal Early

problem

Dietary

consistency

Tube feeding Nothing by

mouth

Handwrit

ing

Normal Slow Not all

legible

Able to hold pen but

not write

Unable to

hold pen

Cutting

food and

feeding

Normal Slow Needs some

help

Food must be cut Need to be

fed

ALS Functional Rating Scale

4 3 2 1 0

Turn in Bed Normal Slow With difficulty Initiate but

not alone

Helpless

Walking Normal Early prob Walks with

assistance

Nonambulat

ory

No purposeful

leg movement

Dressing

and

Hygiene

Normal Effortful Some help Needs

assistance

Total Care

Climbing

Stairs

Normal Slow Mild

unsteadiness

Needs

assistance

Unable to do

Breathing Normal SOBOE SOB at rest Intermittent

ventilator

Ventilator

dependent

Riluzole: inhibits glutamate release, extends life by 3

months

Edaravone: Slows progression as measured by ALSFRS

Unclear if any survival benefits

Treatments

Most ALS Programs will have established pathways for

non-invasive ventilation using BiPAP

Initially used at night

Use may extend into day

Choice to stop BiPAP at this point or any time after

<10% of US patients pursue tracheostomy and

mechanical ventilation

Non-Invasive Ventilation

Physiotherapy

Little high level evidence

Baclofen 10 mg tid up to 80 mg/d

Tizanidine

Benzodiazepines: clonazepam 0.5-2 mg tid

Botulinum toxin

Levetiracetam

Spasticity

Sudden, involuntary, painful contractions

Baclofen, vitamin E, gabapentin (open label evidence)

Quinine sulfate: associated with higher risk of cardiac

arrhythmia and removed from US market

Mexiletine

ECG for prolonged QT

Cramps

Frontotemporal dementia patients early on can be

socially appropriate and not able to reason

Early loss of executive function: use Montreal Cognitive

Assessment Scale

Cognitive impairment present in 50% of patients

Potential Pitfalls

At time of diagnosis, a palliative approach is appropriate

Change in ALS FRS

Progressive weight loss

FVC < 50% or MIP < -60 cmH20

Worsening dysarthria or dysphagia

Serious Illness Triggers

Difficulty communicating

Dyspnea

Choking episodes

Insomnia

Pain

Depression mood (40%), Anxiety (30%) and confusion

(10%)

Common Problems in the Last Month of Life

Early morning HA

Vivid dreaming

Dyspnea on exertion

Inability to lie flat

Nocturnal hypercapnea

Respiratory Impairment

If FVC <50% or MIP < -60 cm H2O

BiPAP is typically organized by the ALS clinic

Improves QOL but does not extend survival for those with

bulbar symptoms

Non-Invasive Ventilation

<10% pursue this option

Patients report sustained QOL

Family report significant decrease in QOL

Tracheostomy and ventilator support

Lung recruitment strategies: partner with respirologist

early in course of illness

Bronchodilators

Glycopyrrolate for sialorrhea: 1-2 mg qid (delirium)

Morphine in low dose for dyspnea

Dyspnea Treatment

Early requests often due to fear or unaddressed

symptoms

Oregon review: ALS second most common condition

Loss of autonomy

Inability to engage in activities

MAID

Medication Oral Rectal IV IM SC

Phenytoin + No + No No

Valproic Acid + + + No No

Levetiracetam + + + + +

Phenobarbital + + + + +

Carbamazepine + + No No No

Midazolam + + + + +

Lorazepam + + + + +

Typical neuroleptics

Atypical neuroleptics – except quetiapine or clozapine

Metoclopramide, nozinan

Nearly all neurologic patients will have dementia at the

end of life – therefore, delirium may not be avoidable if

good pain control is also required

Medications to Avoid with Neurologic Patients

1. People DO die of neurologic illness

2. Symptom burden is high and often over y – decades

3. Symptoms typically include motor and non-motor

4. Treatments may not be compatible with optimal motor

function

5. Treatment may not be typical of the palliative care

toolkit

6. Medications can worsen mental status

Conclusions

References

Thank you

miyasaki@ualberta.ca