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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

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.

Outline• Background

• Pathology of PD

• Medical Management of PD

• PT Management of PD

• Future Directions in PD

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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

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)

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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

PD - Video• PD - Video

• What do you notice about the person’s posture, gait, overall mobility?

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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 Syndromeso 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

Substantia Nigra & the Extrapyramidal System

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Dopamine synthesis

Dopamine pathways in human brain

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.

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Balance &

Falls

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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.

Differential Diagnosis

• Idiopathic PDo No atypical sign

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

• Parkinsonism Syndromeso More symmetricalo 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

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• 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 dysfunctionIII: 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

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

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

DaTscan

Measures of Severity in PD

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

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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

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

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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

Limitations of levodopa

Efficacy tends to decrease as the disease progresses

Chronic treatment associated with adverse events

(motor fluctuations, dyskinesias and

neuropsychiatric problems)

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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.

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

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Physical Therapy Management of Parkinson’s

Disease

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 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.

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Limitations To Current 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.

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. Restorative

3. Compensatory?

1. Compensatory2. Preventative

3. Restorative?

1. Compensatory2. Preventative

Patient/family/caregiver training and educationPsychological support

Referral 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

• Comparing the effects of voluntary exercise (VE)

and forced exercise (FE) on PD symptoms, motor function, and bimanual dexterity

o 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 feedforward 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 BIGoAmplitude 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 PDNational Parkinson Foundation (www.parkinson.org)

American Parkinson Disease Association

(www.apdaparkinson.org)

Davis Phinney Foundation (www.davisphinneyfoundation.org)

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

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

• Know your 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.

http://www.youtube.com/watch?v=pL_LZgAEsnM