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Parkinson’s Disease: what it is and how it is

managed.

An Allied Health Education Webinar

Chad Swank, PT, PhD, NCSCSwank@mail.twu.edu

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Objectives1) Discuss the pathology of Parkinson's disease.

2) Discuss the pharmacological and surgical management of people with PD.

3) Develop suitable physical therapy intervention strategy for people with PD.

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Outline• Background

• Pathology of PD

• Medical Management of PD

• PT Management of PD

• Future Directions in PD

Background

Incidence of PD• 1 to 1.5 million cases in the US

o 60,000 new cases each year

• Typically develops after age 65

• Affects men and women equally

• No social, ethnic, economic boundaries

• More prevalent in industrial countries

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PD facts:

• Direct and indirect costs associated with PD

exceed $20 billion annually in United States

(Weintraub et al., 2008)

o individual costs are 3.3 times higher for

people with PD with cognitive dysfunction

(Vossius et al., 2011)

• With aging population, burden of PD continues

to increase

o Number of PD cases in individuals ≥50 years

predicted to reach 8.7 million worldwide in

next 25 years (Dorsey et al., 2007)

Implications of PD

• People with Parkinson Disease are 5 times more likely to fall

• 70% of people fall more than once per year

• Within 10 years, 25% of people with PD will have a fractured hip

• Hip fractures constitute 47% of total fractures

Pathology of Parkinson’s Disease

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PD - Videos• PD – Video #1

o Reference: (https://www.youtube.com/watch?v=ITv2SJjuAB8)

• PD – Video #2

• What do you notice about the person’s posture,

gait, overall mobility?

What is PD?• Chronic, progressive, neurologic disorder

o Characterized by motor and nonmotor symptoms

o Pathogenesis involves degeneration of dopaminergicneurons in substantia nigra decreasing binding sites for DA.

Types:

• Idiopathic PD

o Most common (78%)

o Late-onset (> 40 yrs)

o Early-onset/ young-onset (< 40)

4-40%

• Secondary PD

o Caused by toxins

• Parkinson’s Plus Syndromes

o Neurodegenerative diseases that cause PD-like symptoms

Basal Ganglia Anatomy

Input

Output •Maintains “readiness”•Modulates spacial orientation-time-force-tone•Cognitive, perceptual emotional, motivation (caudate nucleus)•Planning and programming movement through selection and inhibition of specific motor synergies

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Substantia Nigra & the Extrapyramidal System

Dopamine synthesis

Dopamine pathways in human brain

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Motor Features of PD

Resting tremor1,2

• 70% of patients

• “Pill-rolling” tremor in hands

• Can involve lips, chin, jaw, legs

Bradykinesia1,3,4• 80-90% of patients

• Most disabling symptom of PD

Rigidity1,4

• >90% of patients

• “Cogwheel” (fluctuating) or “lead pipe” (continuous)

Postural instability1

• Indicative of advanced-stage PD

• Frequent cause of fallsPD, Parkinson’s disease.1. Jankovic. J Neurol Neurosurg Psychiatry. 2008;79(4):368-376. 2. Bhidayasiri. Postgrad Med J. 2005;81(962):756-762. 3. Berardelli et al. Brain. 2001;124(pt 111):2131-2146. 4. Weintraub et al. Am J Manag Care. 2008;14(2 suppl):S40-S48.

Postural Instability

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Nonmotor Features of PDPsychiatric disorders1

• Depression in up to 40% of patients

• Anxiety in ~30% of patients

Cognitive disorders1,2

• Mild cognitive impairment

• Dementia in 15-40% of patients

Sleep abnormalities1,3• >70% of patients

• REM sleep behavior disorder

Autonomic dysfunction1-3

• Constipation

• Orthostatic hypotension

Sensory3 • Olfactory dysfunction

Miscellaneous1,2 • Fatigue and weight loss

PD, Parkinson’s disease; REM, rapid eye movement.1. Thanvi et al. Postgrad Med J. 2003;79(936):561-565. 2. Fahn and Sulzer. NeuroRx. 2004;1(1):139-154. 3. Jankovic. J Neurol Neurosurg Psychiatry. 2008;79(4):368-376.

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Differential Diagnosis

• Idiopathic PDo No atypical sign

o No resistance to L-dopa in first 5 years of treatment

• Parkinsonism Syndromeso More symmetrical

o Rapid progression (HY 3 in 3 years)

o Early falls

o Earlier axial involvement

o Associated signs:

• Oculomotor disorders

• Pyramidal signs

• Cerebellar syndromes• Apraxia

• Seizures

• Early cognitive impairment

• Dysautonomia

• Idiopathic PDo Most common at 65%o 2nd cause of motor disability after stroke

• Progressive Supranuclear Palsy (PSP)o 5% of parkinsonism syndromeso Dx made after 3 years; mean survival = 6 years

• Multiple System Atrophy (MSA)o 10% of parkisonism syndromes; mean survival = 9 yearso Atypical progressive presentation

• Corticobasal Degeneration (CBD)o 1% prevelance; onset in 6th decade

• Dementia with Lewy Bodies (DLB)o Combo of cognitive disorders, hallucinations & falls

Prevalence

UK brain bank criteria to Diagnose PD

I: Is Bradykinesia (slowness of movement) present?

II: Are two of the below present?

___ Rigidity (Stiffness in arms, leg, or neck)

___ 4-6 Hertz resting tremor___ Postural instability not caused by primary visual,

vestibular, cerebellar, proprioceptive dysfunction

III: Are at least 3 of the below present?

___ Unilateral onset

___ Rest tremor present

___ Progressive disorder

___ Persistent asymmetry affecting side of onset most

___ Excellent response (70-100%) to levodopa

___ Severe levodopa induced dyskinesia___ Levodopa response for 5 years or more

___ Clinical course of 5 years or more

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FMT-PET images of a healthy individual and PD patients. FMT uptake declines asymmetrically in the early stages, mostly in the posterior putamen.

FMT-PET (6-[18F]fluoro-L-m-tyrosine)

Asari et al. BMC Neurology 2011, 11:35

National Parkinson’s Association: An update on DAT Scanning for Parkinson’s Disease Diagnosis April 2014

DaTscan

Measures of Severity in PD

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Hoehn & Yahr Stages of PD

• Stage I: unilateral

• Stage II: bilateral without impaired balance

• Stage III: bilateral - recovery on pull test

• Stage IV: highly disabled; can still walk

• Stage V: totally disabled

Modified Hoehn and Yahr Staging for Parkinson’s

Stage 0 No signs of disease

Stage 1 Unilateral disease

Stage 1.5 Unilateral plus axial involvement

Stage 2 Bilateral disease, without impairment of balance

Stage 2.5 Mild bilateral disease, with recovery on pull test

Stage 3 Mild to moderate bilateral disease; some postural

instability; physically independent

Stage 4 Severe disability; still able to walk or stand unassisted

Stage 5 Wheelchair bound or bedridden unless aided

UPDRS

• Unified Parkinson’s Disease Rating Scale

• Developed by an international group of neurologists

o UPDRS

- Mentation

- ADL’s, medical complications

- Motor impairment

- Modified HY scale

- Schwab and England ADL Scale

• Interrater reliability: r = 0.8

• Part III correlates well with the HY (r = 0.8)

• Part III can be converted to an HY stage

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Parkinson Disease QuestionnairePDQ-39

• 39 questions• 8 aspects of QOL

o Mobilityo Activities of daily livingo Emotionso Stigmao Social supporto Cognitiono Communicationo Bodily discomfort

• Cronbach’s alpha 0.72–0.95

• Test–retest 0.76–0.93

Hagell & Nygren 2007

PDQ-8

• 8 questions• Relates with PDQ-39

o Pearson's r=0.96, ICC=0.95

Tan et al 2004

Medical Management of Parkinson’s Disease

Use of levodopa

Late 1950s: L-dihydroxyphenylalanine (L-DOPA; levodopa),

a precursor of dopamine that crosses the blood-brain barrier,

could restore brain dopamine levels and motor functions in

animals treated with catecholamine depleting drug

(reserpine)

First treatment attempts in PD patients with levodopa

resulted in dramatic but short-term improvements; took years

before it became an established and successful treatment

Still today, levodopa cornerstone of PD treatment; virtually

all patients benefit

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Limitations of levodopa

Efficacy tends to decrease as the disease progresses

Chronic treatment associated with adverse events

motor fluctuations & dyskinesias

neuropsychiatric problems

decreased bone density

orthostatic hypotension

Pharmacologic Therapies for PD

Pharmacological Management o Levodopa (L-dopa) – act on D1 receptor

• For motor disability

• Sinemet, Parcopa, Sinemet CR, Stalevo

o Dopamine agonist – act on D2 receptor• Stimulates DA receptors

• Lessens motor complications

• May delay use of levadopa

• Miripex, Requip

o MAO-B Inhibitors• Selegiline, Azilect

o COMT-inhibitors• taken with levodopa that can help levodopa work longer and better

• Comtan, Tasmar

o Anticholinergics• Artane, Cogentin

o Others• Amantadine

Side Effects: dyskinesias, nausea, orthostatic hypotension, confusion, hallucinations, headache, agitation, psychosis.

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Dopamine and Gait

• Dopamine improves gait automaticity by altering

striatal, limbic, and cerebellar processing.

Surgical Treatment

• Deep Brain Stimulation (DBS)o Thalamic (Vim DBS): reduces tremor

o Pallidal (GPi DBS): reduces tremor, rigidity, bradykinesia, and gait disorder

o Subthalamic nucleus (STN DBS): reduces tremor, rigidity, bradykinesia, and gait disorder

Physical Therapy Management of Parkinson’s

Disease

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Intervention Framework

Parkinson’s Disease

Indirect Impairments

-Musculoskeletal

-CardiovascularDirect Impairments-Rigidity

-Tremor

-Bradykinesia

-Postural Instability Disability

-Decreased mobility

-Decreased quality of life

-Decreased ADL’s

Medicine

Rehabilitation

What is the Older Evidence?

• Patients with Parkinson’s disease benefit from PT in

addition to standard medications. de Goede et al. Arch Phys Med Rehabil

2001

• Current literature suggests benefits of physical

intervention, but results are not conclusive. Deane KHO et al,

Cochrane Review, 2001

• Exercise, treadmill training, balance training, cued

activities probably effective to improve functional

outcomes, but results not lasting. Suchowersky et al, Neurology 2006

• PT unlikely to influence disease itself but can improve

daily functioning and may influence secondary health

problems. Keus et al. Movement Disorders 2007.

Limitations To Evidence

• Most studies are for individuals in earlier

stages of PD

• Little evidence exists regarding the best

approach for individuals later in the disease

• Recruitment for these studies can be a challenge due to the progressive nature of

the disease.

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Newer Evidence…

Principles for Exercise in PD

• Goal based learning

• Experience-dependent neuroplasticity

• Aerobic training

• Enhanced cognitive engagemento Feedback

o Attentional demand

o Motivation

• Feasibilityo Optimal medication status

Given the Current Evidence ...

• For which patients is physical intervention

appropriate?

• How should the intervention be structured?

• Should the intervention be tailored differently

for patients in different stages of PD?

• What results should be expected from

physical intervention and in each stage?

Theoretical Framework Across Continuum

Disease Stage

Evaluation Findings

Intervention Strategies

Additional Roles and Interventions

Early Stage Middle Stage Late Stage

•Minimal impairments•Minimal activity limitations

•No participation restrictions

•Increasing severity of impairments

•Min/Mod activity limitations

•Min/Mod participation restrictions

•Severe impairments•Severe activity limitations

•Severe participation restrictions

1. Preventative2. Restorative3. Compensatory?

1. Compensatory2. Preventative3. Restorative?

1. Compensatory2. Preventative

Patient/family/caregiver training and educationPsychological supportReferral to other health care professionals

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Early Stage Physical Therapy Interventions

Benefits of Exercise• 2 years of supervised and structured exercise is

effective at improving functional performance outcomes in individuals with moderate PD (Prodoehl et al., 2015)

o Clinicians should include structured and supervised exercise in the long-term plan of care for individuals with PD.

• PRE can significantly improve muscle size, muscle strength, muscle endurance, and neuromuscular function and can significantly impact bradykinesia, postural instability, and patient-perceived quality of life (David et al., 2012)

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Benefits of Exercise• Intensive rehabilitation might slow down the

progression of motor decay, delaying the need for

increasing drug treatment demonstrating a possible

neuroprotective effect (Frazzitta et al., 2015)

Agility Program

Boxing Video

http://www.punchingoutparkinsons.org/

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Middle Stage Physical Therapy Interventions

Treadmill Training for Gait

• Miya et al. 2000o Results: Significantly improved UPDRS total & # steps for BWSTT

• Skidmore et al 2008

o Precautions must be taken to prevent falls &

monitor blood pressure instability during exercise

o Treadmill training is feasible, may reduce

symptom severity, & improve fitness.

Cycling

• Man with bicycle video

Reference: (https://www.youtube.com/watch?v=aaY3gz5tJSk)

• Comparing the effects of voluntary exercise (VE) and forced exercise (FE) on PD symptoms, motor function, and bimanual dexterityo Aerobic fitness improved in PD patients following both VE

and FE interventions.

o Only FE resulted in improvements of motor function and bimanual dexterity.

o FE may lead to a shift in motor control strategy, from feedback to a greater reliance on feed forward processes, suggesting FE may be altering central motor control processes.

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ALBERTS, J.L., S.M. LINDER, A.L. PENKO, M.J. LOWE, and M. PHILLIPS. It is not about the bike, it is about the pedaling: forced exercise and parkinson’sdisease.

Exerc. Sport Sci. Rev., Vol. 39, No. 4, pp. 177Y186, 2011.

Training BIG

oAmplitude of movement important

o Intensity of training

oUses auditory & cognitive cuing

External Cues• External cues are effective for improving the

gait parameters and psychomotor performance of PD patients (Rocha et al., 2014)

• Types of cues:o Visual

o Auditory

o Sensorial

o Cognitive

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Examples of Cueing• Proprioceptive - practice recognizing limb positions with eyes

closed

• Somatosensory – tactile or vibratory

• Cognitive

o Mental simulation

o Rehearsal of movement

• Visual

o Feedback regarding body position using mirrors

o Lines drawn on the floor

o Flashing lights, targets

• Auditory

o Rhythmic acoustic feedback

o Music

o Metronome

Functional Tips/Tricks

• EPDA | COPING STRATEGIES

http://epda.eu.com/copingstrategies/en/category.htm

Example - Getting Up From A Seated Position

• Consider starting position

• Determine efficient strategy

– Use of arms

– To rock or not?

– Counting

• Modify environment

– Chair with higher seat

– Lift chairs

– Chair with handles

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Late Stage Physical Therapy Interventions

Clinical Decisions

• As patients approach later stages of PDo Emphasis shifts from

• correction to compensation

• Patient, family, and care-giver training

o Preventive strategies should be incorporated to minimize sequelae (e.g., hip fracture, pneumonia)

o The role of the caregiver is critical• training for caregiver

• impact on the caregiver should be considered

• strategies should be included to assist the caregiver to meet his/her own needs.

PD-specific Assistive Devices• Things to consider

o Need to address variety of functional l imitations

o Need to be practical!

• 2 references: o Assistive devices alter gait patterns in Parkinson disease: Advantages of the

four-wheeled walker. Kegelmeyer, et al., Gait & Posture 38 (2013) 20-24

o A review of assistive technologies for people with Parkinson’s disease. Cunningham et al., Technology and Health Care 17 (2009) 269-279.

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Measures of Function in PD

NeuroEDGE PD

• http://www.neuropt.org/professional-resources/neurology-

section-outcome-measures-recommendations/parkinson-disease

Future Directions in Parkinson’s Disease

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Case Example• A 78-year-old man presented with a 15-year

history of chronic constipation. At age 68, he experienced a near complete loss of his

sense of smell. Recently, he has developed an unusual sleep disorder, characterized by

abrupt and at times combative behavior during the night that has resulted in injury to

his spouse on two separate occasions; he is referred to a sleep disorders clinic.

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Pharmacological Approach

• Levodopa/carbidopa intestinal gel (LCIG,

marketed as Duodopa®)o developed to minimize the fluctuation in levodopa plasma levels

seen in oral administration by providing a continuous influx of

steady levels of levodopa

o personal pump directly administers the LCIG into the duodenum,

the main site of intestinal absorption

• Proposed benefits include a significant “off” time reduction and dyskinesia along with a

significant improvement in gait disorders and quality of life

Non-invasive Brain Stimulation

Community Based Exercise Programs

• Development of collaborative interventions (i.e.

people with PD, physicians, caregivers, researchers)

to manage PD

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Resources for PDParkinson’s Foundation

• National Parkinson Foundation (www.parkinson.org)

• Parkinson’s Disease Foundation (www.pdf.org)

American Parkinson Disease Association (www.apdaparkinson.org)

Davis Phinney Foundation (www.davisphinneyfoundation.org)

Michael J. Fox Foundation (www.michaeljfox.org)

• Know your local community resources!o support groups for patient and family, free exercise classes, information sessions,

respite care, and other organizations involved within caring for this population in your area.

Questions