Heather Ene, MD

Associate Professor

Univers ity of Colorado Denver

Departments of PMR and Neurology

July 2011

PARKINSON DISEASEDANCE FOR PD WORKSHOP

Normal Motor Control• Central Nervous System

• Premotor, Supplementary Motor and Primary Motor Cortex

• Sensory Cortex

• Limbic System Structures

• Basal ganglia

• Thalamus

• Cerebellum

• Brainstem

• Spinal Cord

• Lower motor and sensory neurons

• Muscle fibers

Multiple Segregated Parallel Loops

Basal Ganglia

• Caudate

• Putamen

• Globus Pallidus

• Subthalamic Nucleus

• Substantia Nigra

Role of the Basal Ganglia • Selection and accentuation of

certain motor patterns, to the exclusion of others• Center-surround concept

• Preparation for movement

• Scaling of speed and amplitude of movement

• Motor learning • Sequencing of motor patterns

• Termination of an ongoing motor program

• Behavioral learning based upon reward• Part of the development of habits/motor

learning

• Sensory processing

Concept of Parkinson Disease

• Widespread neuro-degenerative disorder• Central and peripheral nervous systems involved

• Multiple neurotransmitter systems affected

• Different presenting symptoms & progression• Tremor predominant form

• Postural instability gait disorder form

• Multiple genetic associations

Pathology of PD

•Cumulative loss of dopaminergic neurons in the substantia nigra compacta (SNc) is responsible for key motor features of the PD, particularly bradykinesia.

•Lewy bodies accumulate in multiple brain regions, starting in the brainstem, and affecting multiple neurotransmitter systems (Braak 2003)

• May explain some of the “non-motor” features

Physiology of PD Motor Symptoms*

• Conceptualized as an imbalance between excitatory and inhibitory input from the BG via the thalamus to the cortex.

• The result is excessive inhibition of the cortex.

• *particularly bradykinesia

Early Symptoms

• Decreased sense of smell

• Sleep disorders

• REM d/o

• Excessive daytime sleepiness

• Insomnia

• Shoulder pain

• Restless leg syndrome

• Autonomic dysfunction

• Constipation

• Urinary frequency and urgency

• Sexual dysfunction

• Mood disorders

• Depression, anxiety

Cardinal Motor Features

•4-6 Hz rest tremor– Similar frequency “re-emergent”

postural tremor

•Bradykinesia/hypokinesia – Slowness of initiation of voluntary

movement with progressive reduction in speed and amplitude of repetitive actions

•Rigidity

•Loss of postural reflexes– Generally occurs later in disease

Clinical Diagnosis

•Presence of cardinal motor features.• Early symptoms are often unrecognized as early PD until the motor symptoms

develop.

•Characteristics of symptom onset and progression.

•Response to levodopa (dopamine replacement).

•Lack of features suggesting an alternative diagnosis.

• There are many Parkinson disease mimics.

Adapted from Jankovic 2007

Motor Symptoms Non-motor Symptoms

Tremor, bradykinesia, rigidity, postural instabilityCognitive symptoms: executive dysfunction, bradyphrenia, tip-of-the-tongue (word finding) phenomenon, hallucinations

Hypomimia, dysarthria, dysphagia, sialorrhoeaPsychiatric symptoms: depression, anxiety, apathy, anhedonia, fatigue, impulse control disorder

Decreased arm swing, shuffling gait, festination, difficulty arising from chair and turning in bed

Sensory symptoms: anosmia, ageusia, pain, paresthesias, abnormal eye movements – difficulty reading, defective eye-hand coordination, visual spatial dysfunction, impaired color discrimination

Micrographia, cutting food, feeding, hygiene, slow activities of daily living

Dysautonomia: orthostatic hypotension, constipation, urinary and sexual dysfunction, abnormal sweating, seborrhoea

Melanoma

Weight loss

Glabellar reflex, blepharospasm, dystonia, striatal deformity, scoliosis, camptocormia

Sleep disorders: REM behavior disorder, vivid dreams, daytime drowsiness, sleep fragmentation, restless legs syndrome

Frequent Concerns• Poorly controlled tremor

• Wearing off of medications before next dose

• Dyskinesias

• Falls/near falls

• Orthostatic hypotension (leading to falls)

• Cognitive impairment

• Anxiety

• Pain (often present, but not often mentioned)

Medication Choices

• Degree of disability

• Age of the patient

• Most bothersome symptoms

• Other medical conditions

• Side effect profile

• Risk of medication induced motor fluctuations

• Cost

Pharmacological TreatmentMotor Symptoms

• Dopamine replacement

• Levodopa/Carbidopa (Sinemet)

• Dopamine agonists

• Pramipexole (Mirapex)

• Ropirinole (Requip)

• Rotigotine (Neupro)*

• Bromocriptine (Parlodel)

• Apomorphine (Apokyn)

• COMT Inhibitors

• Entacapone (Comtan)

• Tolcapone (Tasmar)

• MAO B Inhibitors

• Selegiline (Eldepryl and Zelapar)

• Rasagiline (Azilect)

• Anticholingergics

• Trihexyphenidyl (Artane)

• Benztropine (Cogentin)

• Increased dopamine release and decreased reuptake + NMDA receptor blockade

• Amantadine (Symmetrel)

Pharmacological Treatment

COMT = catechol O-methyltransferase, MAO = monoamine oxidase

Deep Brain Stimulation (DBS)

• Electrodes implanted in the subthalamic nucleus (STN) or globus pallidus internus (GPi)

• Leads are tunneled under the skin and connected to a neurostimulator placed under the clavicle.

• Hand held programmer used to adjust stimulation parameters.

• Patients have limited control.

• High-frequency stimulation used for “neuromodulation”• Mechanism of action poorly

understood. • Probably decreases the excessive

output of the basal ganglia upon the thalamus and allows the thalamus to excite the cortex.

DBS Indications

• Advanced PD (?)

• Severe medically “refractory” tremor

• Medication-induced complications impacting quality of life

• Levodopa responsive impairments• Except tremor

• Cognitively intact

• Absence of significant or uncontrolled psychiatric problems

• Realistic expectations

DBS Outcomes• Increased “on time”

• Decreased rigidity, bradykinesia, akinesia and tremor

• Decreased medication use and medication-induced dyskinesia

• Improved quality of sleep and total sleep time

• Decreased pain???

DBS Outcomes• Variable effect upon postural instability and speech

impairment – can be worse!!!!!

• Possible cognitive decline - temporary or permanent

• Depression and anxiety may increase if dopaminergic medications are significantly reduced

• Impulse control problems

• Significant weight gain

Restorative Surgery

• Experimental

• Gene transfer

• Stem cell transplantation

Exercise

• Possible neuroprotective effects - particularly high intensity aerobic activity.

• Possible pro-degenerative effects of inactivity

• Management of PD motor symptoms.

• Ex. Tremor, rigidity, bradykinesia

• Management of PD nonmotor symptoms.

• Ex. Depression, anxiety, sleep dysregulation, pain

Skilled Therapies

• Improve strength and activity tolerance

• Teach “tricks” for overcoming or adapting to motor limitations

• Provide education patient and family on strategies to accomplish activities of daily living (ADLs)

• Access appropriate adaptive equipment and orthotics

Aerobic Training for PD

• Treadmill training is associated with:

• Improved overall aerobic conditioning

• Decreased energy expenditure during walking

• Improved overground gait measures, including increased speed and stride length

Aerobic Training for PD

• Body Weight Supported Treadmill:

• Increased speed

• High repetition

• Active engagement

• Sensory experience of more normal gait mechanics

• Multisensory cues

• Task-specific training

Aerobic Training for PD

• Cycling:

• Improved aerobic conditioning

• Forced-cycling at a high pedaling rate is associated with:

• Off medications improvements in tremor, rigidity and bradykinesia

• Improved upper extremity function

Resistance Training

• Evidence for primary weakness, in addition to deconditioning.

• The weakness may contribute to postural instability.

• Weakness + slowness may also contribute to difficulties with sit-stand transfers, gait and stair climbing.

Resistance Training

• Progressive resistance exercises are safe, well tolerated and are associated with:

• Increased strength in target muscles

• Improved sit-stand transfers

• Improved balance

• Improved gait velocity and stride length

Spinal Flexibility Programs

• Spinal range of motion is decreased even in early PD.

• Poor spinal flexibility is associated with decreased balance.

• Spinal flexibility can be improved with targeted exercise.

• Interventions include:

• Schenkman’s Axial Mobility Program, NPF Fitness Counts Program, PD yoga classes, Tai Chi, Quigong, Dance

Rhythmic Cueing

• Use of external auditory stimuli to facilitate movement initiation and continuation.

• Rhythmic pacing alone (metronomic) or embedded.

• Postulated to “circumvent disordered circuitry and entrain rhythmic motor responses”, perhaps via cerebellar connections to premotor cortex.

Rhythmical Cueing

• Associated with rapid improvements:

• Increased gait velocity and stride length

• Increased step cadence (number of steps/time)

• Improved lower extremity muscle activation patterns

• Improved postural instability and gait scores on UPDRS

• Modest decrease in freezing of gait (FOG) severity

Visual Cueing

• Use of lines drawn ┴ to direction of gait to increase gait speed and step length.

• U-Step laser cane or laser walker for FOG.

Dance

•Combination of rhythmic, visual and tactile cueing

•Social contact

•Emotional responseMark Morris Dance Group

Dance

•Hackney 2007:• Twenty 1 hour sessions of Argentine Tango over 13

weeks (n=9) v. structured strength and flexibility program (n=10).

• Both groups showed significant improvements in UPDRS III, a trend toward decreased FOG, and slight improvement in gait velocity.

• Tango group showed additional improvements in Berg Balance Test and a trend toward improvement in the Timed Up and Go Test.

Dance• Hackney 2009

• Twenty 1 hour sessions of Argentine Tango (n=14) v. twenty 1 hour sessions of Fox Trot over 13 weeks (n=17 ) v. no intervention (n=17).

• Both dance groups showed significant improvements in the Berg Balance Scale, 6- minute walk distance, and backward stride length .• No improvement seen in controls

• Tango group showed improvement in FOG• No improvement in Fox Trot group and worsening in controls

• Controls showed sign worsening on UPDRSIII

Amplitude-Specific Training

• Bradykinesia and hypokinesia are cardinal features of PD.

• Faulty sensorimotor processing leads to reduced gain in the motor command for selecting and reinforcing movement amplitude.

• Part of the problem may be related to abnormal perception of the energy cost of the movement

Amplitude-Specific Training

•LVST/LOUD (Lee Silverman Voice Treatment)

• Consciously increasing volume

• Modification of speech patterns• Ex. use of shorter sentences

• Breathing exercises

• Range-of-motion exercises for the muscles of speech

• Significant long-term (2 years) improvements in vocal loudness and speech intelligibility

• Transfer of improvements from LVST to swallow and facial expression

Amplitude-Specific Training•Training BIG• Based upon observation that speed increases with

increased movement amplitude.

• Use of repetitive large amplitude full body movements, with directed attention to the feeling of “moving big”.

• May be most effective for earlier stage of PD.• Possibly due to increasing impairment of directed attention in later

stages.

• Transfer of cued repetitive movement to un-cued functional tasks (reaching and gait) observed.

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References• Hirsch MA HF, Hirsch HVB. From Research to Practice: Rehabilitation of

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• Iansek R. Interdisciplinary Rehabilitation in Parkinson’s Disease. Parkinson’s Disease; Advances in Neurology. Lippincott, Williams and Wilkins. 1999;Chap 76:555-559.

• Johnell O, Melton LJ, Atkinson EJ.. Fracture risk in patients with parkinsonism: a population based study in Olmstead County, Minnesota. Age Ageing1992;21:32-38.

• Kern DS and Kumar R. Deep brain stimulation. The Neurologist 2007;13:237-252.

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• Lim I, van Wegen E, de Goede C, Deutekom M, Nieuwboer A, Willems A, Jones D, Rochester L, Kwakkel G. Effects of external rhythmical cueing on gait in patients with Parkinson’s disease: a systematic review. Clin Rehabil2005;19:695-713.

• Liotti M, Vogel D, Brown S Hypophonia in Parkinson’s disease: neural correlates of voice treatment revealed by PET. Neurology 2003;60:432-440.

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• Schenkman M, Morey M, Kuchibhalta. Spinal flexibilit and balance control among community-dwelling adults with and without Parkinson’s disease. J Gerontol MS2000;55:M441-445.

• Schenkman M, Cutson TM, Maggie K, Chandler J, Pieper CF, Ray L, Laub KC. Exercise to improve spinal flexibility and function for people with Parkinson’s Disease: a randomized, controlled trial. J Am Geriatric Soc 1998;46:1207-1216.

• Sideway B, Anderson J, Danielson G, Martin L, Smith G. Effects of long-term gait training using visual cues in an individual with Parkinson Disease. Phys Ther.2006;86:186-194.

• Smith AD, Zigmond MJ. Can the brain be protected through exercise? Lessons from an animal model of parkinsonism. Exp Neurol 2003;184(1):31-39.

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• Tillerson J, Cohen A, Caudle M, Zigmond M, Shallert T. Forced nonuse in unilateral parkinsonian rats exacerbates injury. J Neurosci 2002;22(15):6790-6799.

• Tillerson J, Cohen A, Philhower J, Miller G, Zigmond M, Shallert T. Forced limb-use effects on the behavioural and neurochemical effects of 6-hydroxydopamine. J Neurosci2001;21(12):4427-4435.

• Tillerson JL, Cohen WM, Reveron ME, Miller GW. Exercise induces behavioral recovery and attenuates neurochemical deficits in rodent models of Parkinson’s disease. J Neurosci 2003;119:899-911.

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