PARKINSONS DISEASE RESEARCH, EDUCATION, AND CLINICAL CENTER HOUSTON VA MEDICAL CENTER

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PARKINSONS DISEASERESEARCH, EDUCATION, AND
CLINICAL CENTERHOUSTON VA MEDICAL CENTER
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PARKINSONSDISEASERecent Advances in Therapy
Eugene C. Lai, M.D., Ph.D. Baylor College of
Medicine Houston VA Medical Center
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PARKINSONS DISEASEClassical Clinical Features

• Resting Tremor
• Cogwheel Rigidity
• Bradykinesia
• Postural Instability

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PARKINSONS DISEASEAssociated Clinical Features

• Micrographia
• Hypophonia
• Hypomimia
• Shuffling gait / festination
• Drooling
• Dysphagia
• Autonomic dysfunction
• Depression
• Dementia

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PARKINSONS DISEASE

• Parkinsons disease is a progressive
• neurodegenerative disease. Although
• treatment is available to achieve symptomatic
  improvement, its management is both a challenge
  and an art. Care of patients with advanced
  disease need clinical experience,
• patient cooperation and utilization of all
  available treatment options.

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PARKINSONS DISEASEIncidence and Epidemiology
Prevalence Rate 200 per 100,000 Rare for
individuals lt 40 years of age 1 for
individuals gt 60 years of age 2 for
individuals gt 85 years of age Men gt
Women Incidence rate 20 per 100,000 (annually)
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How common is Parkinsons disease?

• The National Parkinsons Foundation estimates
  that up to 1.5 million Americans have the disease
• Approximately 50,000 new cases are diagnosed each
  year

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STAGES OFPARKINSONS DISEASE

• EARLY - no functional impairment
• MILD - honeymoon period
• MODERATE - multiple drugs, occupational and
  social activities affected
• SEVERE - side effects from drugs, resistant to
  therapy, reduced quality of life
• LATE - dependent in ADL, wheelchair or bed bound

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PARKINSONS DISEASEPathophysiology

• Involvement of Basal Ganglia, primarily
  Substantia Nigra and Globus Pallidus
• Depletion of CNS dopamine
• Imbalanced cholinergic/dopaminergic transmission

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TREATMENT OPTIONSOF A PARKINSONS DISEASE

• Pharmacological treatments
• Non-pharmacological treatments
• Surgical treatments

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PARKINSONS DISEASEDrug Therapy

• Monoamine oxidase-B inhibitor
• Levodopa
• Anticholinergics
• Dopamine agonists
• COMT inhibitor

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PHARMACOLOGIC MANAGEMENT OF PARKINSONS DISEASE
Without functional disability
Selegiline ?
With mild functional disability
Amantadine Trihexyphenidyl Tricyclics Dopamine
agonist
With moderate functional disability
Carbidopa/levodopa Dopamine agonist COMT inhibitor
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COMPLICATIONS IN ADVANCEDPARKINSONS DISEASE

• Motor fluctuations
• Dyskinesias
• Posture, gait, falling
• Neuropsychiatric problems
• Sleep disorders
• Sensory phenomena
• Dysautonomias
• Speech disturbances

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MOTOR FLUCTUATIONS

• Unpredictable response
• No on response
• Wearing off
• Complex on-off oscillations
• Freezing

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DYSKINESIA

• Peak dose dyskinesia
• Dyskinesia-improvement-dyskinesia
• Dystonia
• Complex movements

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GENERAL TREATMENT STRATEGIES FOR MOTOR
COMPLICATIONS

• Individualize treatment
• Adjust medication combination
• Substitute controlled-release with regular
  levodopa
• Dose levodopa regularly
• Smaller doses of levodopa increase frequency
• Increase GI transit time
• Modify distribution of dietary protein

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SPECIFIC TREATMENT STRATEGIES FORMOTOR
COMPLICATIONS

• Adjust levodopa dosage
• Maximize dopamine agonist
• Add COMT inhibitor
• Simplify medication regimen
• Amantadine or clozapine for dyskinesia
• Anxiolytics

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POSTURAL INSTABILITY, GAIT IMBALANCE, AND FALLING

• Start hesitation
• Retropulsion
• Festination
• Rigidity
• Freezing
• Orthostatic hypotension
• Associated neurologic deficits
• Orthopedic symptoms
• Environmental causes

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TREATMENTS TO IMPROVE MOBILITY AND AVOID FALLS

• Keep active
• Exercise regularly
• Physical therapy
• Adjust medication regimen
• Sensory cues
• Assistive devices
• Safety-proof living environment

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NEUROPSYCHIATRIC PROBLEMS INPARKINSONS DISEASE

• Depression
• Hallucination/delirium
• Behavioral fluctuation -Anxiety/panic -Agitation
• Cognitive impairment

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TREATMENT OF NEUROPSYCHIATRIC PROBLEMS IN
PARKINSONS DISEASE

• Antidepressants
• Reduce/discontinue medications
• Atypical neuroleptics
• Counseling
• Anxiolytics
• Keep active/exercise
• Educate caregivers

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SLEEP DISORDERS IN PARKINSONS DISEASE

• Insomnia
• REM behavior disorder
• Nightmares
• Obstructive sleep apnea
• Excessive daytime sleepiness

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TREATMENT OF SLEEP DISORDERS IN PD

• Treat depression/anxiety
• Add controlled-release levodopa at bedtime
• Sleep hygiene program
• Short-acting sedative hypnotics
• Minimize nocturia
• Clonazepam for RBD
• Discontinue tricyclic drugs and MAO inhibitors
• Avoid stimulants in evening
• Evaluate sleep disorder
• Judicious use of stimulants for EDS

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SENSORY PHENOMENA IN PARKINSONS DISEASE

• Rigidity/cramps
• Dystonic pain
• Musculoskeletal pain associated with immobility
• Heaviness in limbs

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TREATMENT OF SENSORY PHENOMENA IN PD

• Stretching exercises
• Medication adjustment
• Physical therapy
• Baclofen
• NSAIDs
• Botulinum toxin injection

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DYSAUTONOMIAS IN PARKINSONS DISEASE

• Constipation
• Urinary problems
• Sexual problems
• Orthostatic hypotension
• Impaired thermoregulation
• Dysphagia
• Siarrhea/drooling

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SPEECH DISORDER IN PARKINSONS DISEASE

• Hypokinetic dysarthria
• Lack of control of speaking rate
• Monotone
• Hoarse/breathy voice
• Stuttering
• Hypophonia
• Imprecise pronunciation/mumbling

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TREATMENT OF SPEECH DISORDER IN PD

• Behavioral (drill, exercise)
• Instrumental (prosthetics, amplifier)
• Surgical
• Pharmaco-therapeutic

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NON-PHARMACOLOGIC INTERVENTIONS IN PD

• Education
• from healthcare providers support groups
• avoid misinformation incomplete information
• Support
• professional peer support
• emotional financial counseling
• Exercise
• keep active avoid deconditioning
• regular stretching exercises
• physical therapy
• Nutrition
• balanced diet suitable consistency
• nutritional counseling

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MEDICALLY REFRACTORY SYMPTOMS OF ADVANCED PD

• Dopa-induced dyskinesia
• Excessive tremor
• On-off motor fluctuation
• Rigidity with pain
• Freezing

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Surgical Treatments for Parkinsons Disease

• Ablative
• Thalamotomy, Pallidotomomy
• Electrical Stimulation
• VIM Thalamus, GPi, STN
• Transplant
• Autologous Adrenal, Human Fetal, Xenotransplants,
  Genetically Engineered Transplants
• Intrathecal Drugs

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Deep Brain Stimulation
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DEEP BRAIN STIMULATION (DBS)

• High frequency, pulsatile electrical stimulation
• Stereotactically placed into target nucleus
• Can be activated and deactivated by an external
  magnet
• Exact physiology unknown, but higher frequencies
  mimic cellular ablation, not stimulation

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EFFICACY OF DEEP BRAIN STIMULATION (DBS)

• Thalamic DBS is a safe and effective treatment
  for medically refractory ET and PD tremor
• It can be performed bilaterally
• The precise mechanism of action is unknown
• DBS of GPi STN seems to improve all aspects of
  PD motor symptoms