Parkinson’s DiseaseAlvin B. Lin, MD, FAAFPCAQ Geriatric MedicineSolo Practice, Las Vegas, NV

Disclosure StatementIt is the policy of the AAFP that all individuals in a position to control content disclose any relationships with commercial interests upon nomination/invitation of participation. Disclosure documents are reviewed for potential conflicts of interest. If conflicts are identified, they are resolved prior to confirmation of participation. Only participants who have no conflict of interest or who agree to an identified resolution process prior to their participation were involved in this CME activity.

All faculty and staff in a position to control content for this session have indicated they have no relevant financial relationships to disclose.

Learning Objectives

1. Distinguish Parkinson’s disease from other gait & movement disorders

2. Describe non-motor signs of Parkinson’s disease3. Select appropriate management strategies for patients

w/Parkinson’s disease, including assessment of (non)pharmacologic treatments

4. Recognize challenges in managing advanced stages of Parkinson’s disease

Distinguish Parkinson’s disease from other gait & movement disorders

AES Question

Question 1Your established 70yo M who is otherwise remarkably healthy presents c/o tremors improved w/glass of wine. What else might confirm Parkinson’s disease rather than essential tremor?

A. Involvement of head & voiceB. Worsening upon intentionC. Normal gait & balanceD. All of the aboveE. None of the above

Compare & Contrast

Parkinson’s diseaseMost often presents

unilaterallyMost commonly occurs at

restTremor, when present,

doesn’t affect head or voice

Essential TremorGenerally presents

bilaterallyPrimarily seen during

actionAffects hands, legs, head

& voice

Differential Diagnosis

Essential tremorNormal pressure hydrocephalusDementia w/Lewy bodiesMultiple system atrophyCorticobasal syndromeProgressive supranuclear palsy

Differential Diagnosis

Essential tremorNormal pressure hydrocephalusWet, wobbly & wacky ie incontinence, gait impairment &

cognitive impairmentDementia w/Lewy bodiesMultiple system atrophyCorticobasal syndromeProgressive supranuclear palsy

Differential Diagnosis

Essential tremorNormal pressure hydrocephalusDementia w/Lewy bodies Typically first causes cognitive impairment & hallucinations

followed by parkinsonism later onMultiple system atrophyCorticobasal syndromeProgressive supranuclear palsy

Differential Diagnosis

Essential tremorNormal pressure hydrocephalusDementia w/Lewy bodiesMultiple system atrophyParkinsonism plus ataxia, autonomic dysfunction esp

orthostasis & incontinenceCorticobasal syndromeProgressive supranuclear palsy

Differential Diagnosis

Essential tremorNormal pressure hydrocephalusDementia w/Lewy bodiesMultiple system atrophyCorticobasal syndromeParkinsonism plus dystonia, myoclonus, apraxia & aphasia

Progressive supranuclear palsy

Differential Diagnosis

Essential tremorNormal pressure hydrocephalusDementia w/Lewy bodiesMultiple system atrophyCorticobasal syndromeProgressive supranuclear palsyParkinsonism plus frequent falls early on, limited eye mvmts,

dysphagia, dysarthria & sleep problems

Describe non-motor signs of Parkinson’s disease

AES Question

Question 2Your now 75yo M w/Parkinson’s disease is worried about issues affecting his quality of life. Which of the following are non-motor symptoms of Parkinson’s?

A. Vivid dreams & hallucinationsB. Apathy & depressionC. ConstipationD. OrthostasisE. C & DF. All of the above

Back to BasicsParkinson’s disease Neurodegenerative disorder affecting dopamine-producing

substantia nigraMotor symptoms vary but may include Tremor, mainly at rest, ie pill rolling Often decreases or even disappears w/action or sensory stimulation

Bradykinesia Limb rigidity c/o “stiffness”: classic cogwheel esp by clenching contralateral fist

Gait & balance problems

Back to Basics

Parkinson’s disease Neurodegenerative disorder affecting dopamine-producing

substantia nigraNon-motor symptoms vary but may include Apathy & depression Bowel and/or bladder issues esp constipation & incontinence Sleep behavior disorders Loss of sense of smell and/or taste Cognitive impairment Hallucinations & delusions

Select appropriate management strategies for patients w/Parkinson’s disease, including assessment of (non)pharmacologic treatments

AES Question

Question 3Your now 77yo M w/confirmed Parkinson’s disease c/o functional loss enough that he’s read to consider pharmacologic options. Should you offer him:

A. AmantadineB. ApomorphineC. Carbidopa/LevodopaD. RopiniroleE. Selegiline

Therapeutic Options

IatrogenicPharmacologicNonpharmacologic

Therapeutic Options

IatrogenicPrevent head traumaStop antipsychotics & antiemetics if possible

PharmacologicNonpharmacologic

Therapeutic Options IatrogenicPharmacologic Levodopa (plus Carbidopa)Dopamine agonistsAmantadineAdenosine A2a antagonistsCOMT inhibitorsAnticholinergicsMAO-B inhibitors

Nonpharmacologic

Therapeutic Options IatrogenicPharmacologicNonpharmacologicPhysical therapy Exercise at least 2.5hr/wk incl Tai Chi, yoga, Pilates, dance, etc Smaller decline in mobility & QoL over 2yrs c/w no exercise

Occupational therapySurgical optionsMedicinal cannabisOTCs

Therapeutic Options

IatrogenicPharmacologicNonpharmacologic Physical therapyOccupational therapy Surgical optionsMedicinal cannabis Parkinson’s Foundation Consensus Statement on Use of Medicinal

Cannabis for Parkinson’s Disease https://bit.ly/2TiqfY7OTCs

Therapeutic Options IatrogenicPharmacologicNonpharmacologicPhysical therapyOccupational therapySurgical optionsMedicinal cannabisOTCs No evidence base to demonstrate effectiveness No quality control during manufacture

Pharmacologic OptionsLevodopa (plus Carbidopa) Converted to dopamine in brain Tremendous nausea & vomiting w/o Carbidopa blocking

peripheral conversionDopamine agonistsAmantadineAdenosine A2a antagonistCOMT inhibitorsAnticholinergicsMAO-B inhibitors

Pharmacologic OptionsLevodopa (plus Carbidopa) Disintegrating, immediate release, controlled release & extended

release formulations not necessarily interchangeableDopamine agonistsAmantadineAdenosine A2A antagonistCOMT inhibitorsAnticholinergicsMAO-B inhibitors

Pharmacologic OptionsLevodopa (plus Carbidopa) Disintegrating (Parcopa), immediate release (Sinemet), controlled

release (generic C/L CR) & extended release (Rytary) formulations not necessarily interchangeable

Dopamine agonistsAmantadineAdenosine A2A antagonistCOMT inhibitorsAnticholinergicsMAO-B inhibitors

Pharmacologic OptionsLevodopa (plus Carbidopa)Also available in combo w/Entacapone (dopamine agonist)

Dopamine agonistsAmantadineAdenosine A2A antagonistCOMT inhibitorsAnticholinergicsMAO-B inhibitors

Pharmacologic OptionsLevodopa (plus Carbidopa)Dopamine agonistsPramipexole, Ropinirole, Apomorphone (PO & IM) &

Rotigotine (transdermal)AmantadineAdenosine A2a antagonistCOMT inhibitorsAnticholinergicsMAO-B inhibitors

Pharmacologic OptionsLevodopa (plus Carbidopa)Dopamine agonistsAmantadine IR (Symmetrel) & ER (Gocovri & Osmolex)

Adenosine A2a antagonistCOMT inhibitorsAnticholinergicsMAO-B inhibitors

Pharmacologic OptionsLevodopa (plus Carbidopa)Dopamine agonistsAmantadineAdenosine A2a antagonist Istradefylline (Nourianz)

COMT inhibitorsAnticholinergicsMAO-B inhibitors

Pharmacologic OptionsLevodopa (plus Carbidopa)Dopamine agonistsAmantadineAdenosine A2a antagonistsCOMT inhibitors Blocks Levodopa metabolism Entacapone (Comtan), Opicapone (Ongentys) & Tolcapone

(Tasmar)AnticholinergicsMAO-B inhibitors

Pharmacologic OptionsLevodopa (plus Carbidopa)Dopamine agonistsAmantadineAdenosine A2a antagonistsCOMT inhibitorsAnticholinergicsBenztropine (Cogentin) & Trihexyphenidyl (fka Artane)

MAO-B inhibitors

Pharmacologic OptionsLevodopa (plus Carbidopa)Dopamine agonistsAmantadineAdenosine A2a antagonistsCOMT inhibitorsAnticholinergicsMAO-B inhibitorsRasagiline (Azilect), Safinamide (Xadago) & Selegiline

(Eldepryl & Zelapar),

Non-pharmacologic Options

Brain surgeryGI surgery

Non-pharmacologic Options

Brain surgeryDeep brain stimulationPallidotomy ThalamotomyUltrasound

GI surgery

Non-pharmacologic OptionsBrain surgeryDeep brain stimulation Approved 1997 for tremor Approved 2002 for advanced symptoms Approved 2016 for earlier stages Benefits last 5+yrs but not a cure & doesn’t slow progression

Pallidotomy ThalamotomyUltrasound

GI surgery

Non-pharmacologic OptionsBrain surgeryDeep brain stimulation Most effective for people w/

Disabling tremors Wearing-off spells Medication-induced dyskinesias

Doesn’t improve speech, swallowing, cognition or gait freezingPallidotomy ThalamotomyUltrasound

GI surgery

Non-pharmacologic OptionsBrain surgery Deep brain stimulation Pallidotomy Surgical lesion placed at contralateral globus pallidus Improves severe motor fluctuations ie dyskinesia & on/off responses from

long-term Levodopa Improves tremor, stiffness/rigidity & bradykinesia no longer managed by

medications Not a good option if haven’t responded to Levodopa

Thalamotomy Ultrasound

GI surgery

Non-pharmacologic OptionsBrain surgeryDeep brain stimulationPallidotomy Thalamotomy Surgical lesion at contralateral thalamus Improves severe tremor not responsive to meds Doesn’t improve bradykinesia, speech or gait difficulties May perform bilaterally but incr risk of speech & cognitive

impairmentUltrasound

GI surgery

Non-pharmacologic Options

Brain surgeryDeep brain stimulationPallidotomy ThalamotomyUltrasound FDA approved using transducer helmet to focus u/s energy to lesion

specific tremor inducing sites ID’d by MRI Not recommended if very thick skull or can’t undergo MRI

GI surgery

Non-pharmacologic Options

Brain surgeryGI surgeryDuopa is C/L in gel form delivered enterally via PEG/J tube

via cassette/pumpCandidate if responds to Levodopa but 3+hrs off time &

failed dopamine agonists or MAO-B inhibitors

Recognize challenges in managing advanced stages of Parkinson’s disease

AES Question

Question 4Family of your now 85yo M w/confirmed Parkinson’s disease report difficulty caring him b/c he’s very forgetful, paranoid from hallucinations, sleeps during the day & is up all night, falls frequently, and coughs during meals. Options to stage PD include:

A. Parkinson’s FoundationB. Hoehn & YahrC. UPDRSD. All of the above

Staging Parkinson’s Disease

Parkinson’s FoundationHoehn & YahrUPDRS (Unified Parkinson’s Disease Rating Scale)

Staging Parkinson’s Disease

Parkinson’s FoundationStage 1 mild symptoms don’t interfere w/ADLs, typically

unilateralStage 2 worsening symptoms, typically bilateral, still lives

aloneStage 3 mid-stage, loss of balance & bradykinesia w/falls,

remains independentHoehn & YahrUPDRS (Unified Parkinson’s Disease Rating Scale)

Staging Parkinson’s Disease

Parkinson’s FoundationStage 4 severe & limiting symptoms, requires DME for

mobility, needs assist w/ADLs, unable to live aloneStage 5 requires wc or is bedridden, hallucinations &

delusionsHoehn & YahrUPDRS (Unified Parkinson’s Disease Rating Scale)

Staging Parkinson’s Disease

Parkinson’s FoundationHoehn & Yahr (1967)Stage 1 Unilateral involvement only usually with minimal or

no functional disabilityStage 2 Bilateral or midline involvement without impairment

of balanceStage 3 Bilateral disease: mild to moderate disability with

impaired postural reflexes; physically independentUPDRS (Unified Parkinson’s Disease Rating Scale)

Staging Parkinson’s Disease

Parkinson’s FoundationHoehn & Yahr (1967)Stage 4 Severely disabling disease; still able to walk or stand

unassistedStage 5 Confinement to bed or wheelchair unless aided

UPDRS (Unified Parkinson’s Disease Rating Scale)

Staging Parkinson’s Disease

Parkinson’s FoundationHoehn & Yahr (modified 1983)Stage 1 Unilateral involvement onlyStage 1.5 Unilateral and axial involvementStage 2 Bilateral involvement without impairment of balanceStage 2.5 Mild bilateral disease with recovery on pull test

UPDRS (Unified Parkinson’s Disease Rating Scale)

Staging Parkinson’s Disease

Parkinson’s FoundationHoehn & Yahr (modified 1983)Stage 3 Mild to moderate bilateral disease; some postural

instability; physically independentStage 4 Severe disability; still able to walk or stand

unassistedStage 5 Wheelchair bound or bedridden unless aided

UPDRS (Unified Parkinson’s Disease Rating Scale)

Staging Parkinson’s Disease

Parkinson’s FoundationHoehn & YahrUPDRS (Unified Parkinson’s Disease Rating Scale)Gold standard for Neurologists 6 segments Mentation, Behavior, and Mood ADL Motor sections

Staging Parkinson’s Disease

Parkinson’s FoundationHoehn & YahrUPDRS (Unified Parkinson’s Disease Rating Scale)Gold standard for Neurologists 6 segments Complications of Therapy (in the past week) Modified Hoehn and Yahr Scale Schwab and England ADL scale

Challenges in Advanced Parkinson’s

ConstipationDementiaDepression & anxietyDroolingFatigueOrthostatic hypotensionPsychosis (hallucinations and/or delusions)

Challenges in Advanced Parkinson’s

Constipation Lifestyle changes Exercise Diet (high fiber w/plenty of fluids)

Over-the-counter optionsPrescription options

Challenges in Advanced Parkinson’s

Constipation Lifestyle changesOver-the-counter options Fiber supplements Stool softeners Laxatives Enemas

Prescription options

Challenges in Advanced Parkinson’s

Constipation Lifestyle changesOver-the-counter optionsPrescription options Nothing approved for PD assoc constipation Linaclotide (Linzess) Lubiprostone (Amitiza) Plecanitide (Trulance)

Challenges in Advanced Parkinson’s

Dementia Typically occurs late in course of PD For semantics, dementia that occurs early, prior to or within 1st year

of parkinsonism symptoms, is labeled Lewy body dementiaOnly Rivastigmine (Exelon) is approved for PD dementiaBut could also consider Donepezil (Aricept) Or Galantamine (Razadyne)

And Memantine (Namenda)

Challenges in Advanced Parkinson’s

Depression & anxietyMost commonly used SSRIs & SNRIs Paroxetine (Paxil) & venlafaxine (Effexor XR) have each

demonstrated improvement in mood w/o worsening motor symptomsBe careful re benzodiazepine use as these can cause

confusion, sleepiness & imbalance

Challenges in Advanced Parkinson’s

DroolingSide effect of decr swallowing frequencyCan be embarrassing & socially isolatingAlways weigh benefits vs risks Botulinum toxin injections

IncobotulinumtoxinA (Xeomin) RimabotulinumtoxinB (Myobloc)

Anticholinergics Trihexyphenidyl (fka Artane) Glycopyrrolate (fka Robinul)

Challenges in Advanced Parkinson’s

FatigueDifficult to describeMore than drowsiness or extreme tirednessBehavioral strategies Regular exercise Short naps

Manage comorbiditiesPrescription options

Challenges in Advanced Parkinson’s

FatigueDifficult to describeMore than drowsiness or extreme tirednessBehavioral strategiesManage comorbidities Sleep problems Depression

Prescription options

Challenges in Advanced Parkinson’s

FatigueDifficult to describeMore than drowsiness or extreme tirednessBehavioral strategiesManage comorbiditiesPrescription options Stimulants

Methylphenidate (Ritalin) etc Wakefulness promoting agents Etc

Challenges in Advanced Parkinson’s

FatigueDifficult to describeMore than drowsiness or extreme tirednessBehavioral strategiesManage comorbiditiesPrescription options Stimulants Wakefulness promoting agents

Modafinil (Provigil) etc Etc

Challenges in Advanced Parkinson’s

FatigueDifficult to describeMore than drowsiness or extreme tirednessBehavioral strategiesManage comorbiditiesPrescription options Stimulants Wakefulness promoting agents Etc

IR amantadine, Rasagiline (Azilect) & selegiline may decr fatigue in add’n to PD motor symptoms

Challenges in Advanced Parkinson’s

Orthostatic hypotensionBehavioral changesDietary changesPrescriptions options Droxidopa (Northera) converts into norepinephrine Fludrocortisone (Florinef) Midodrine (ProAmatine)

Challenges in Advanced Parkinson’s

PsychosisHallucinations – seeing/hearing things that aren’t thereDelusions – false, often paranoid, beliefsAs always, must weigh risks vs benefitsAll antipsychotics carry “black box” warning re incr risk of

death in elderly w/dementiaDiscuss w/ and educate family re egosyntonic vs

egodystonic symptomsConsider pimavanserin (Nuplazid), quetiapine (Seroquel) or

clozapine (Clozaril)

Challenges in Advanced Parkinson’s

Consider for hospice or palliative care if Male, >61yo at onset, currently 75-85yo w/accelerated decr

in BMI, complicated by CAD/CVD, CHF, DM & pressure ulcersWorsening motor symptoms & global disability Fractures in last 3-5yrsDysphagia w/pneumoniaDementia +/- hallucinations Incontinence +/- urosepsis

https://jnnp.bmj.com/content/jnnp/92/6/629.full.pdf

Practice Recommendations

Look for Parkinson disease motor symptoms esp as part of fall evaluationLook for Parkinson disease non-motor symptoms esp in

those w/constipation, drooling, hallucinations/delusions & orthostatic hypotensionConsider & discuss palliative care or hospice in

advance stages

Answers

1. E2. F3. C4. D