1. Parkinson’s Disease Definitions Disease features Pathology
Epidemiology
Treatments

2. (‘lead-pipe’ or ‘cog-wheel’)
PARKINSONISM
(‘pill-rolling’)
(slowed movement)
(‘lead-pipe’ or ‘cog-wheel’)

3. Dx of Parkinson’s Disease

4. Clinical Features: Secondary motor symptoms
Freezing
Micrographia
Masked faces
Unwanted accelerations
Rapid stammering speech
Festinating gait
Stooped posture
Dystonia
Impaired motor dexterity/coordination
Poverty of movement (decreased arm swing)
Akathisia
Speech problems
Hypophonia
Slurred
aprosody
Difficulty swallowing
Drooling

5. Clinical Features: Non-motor symptoms
Early
Later
sleep disturbances
incontinence
sexual problems
excessive saliva
weight loss or gain
fatigue
Cognitive impairment
memory difficulties, slowed thinking, confusion, dementia
Psychiatric
Depression, anxiety
loss of sense of smell
constipation
REM behavior disorder
mood disorders
orthostatic hypotension

6. Parkinsonian Syndromes
Idiopathic
Parkinson’s Disease
Symptomatic
Infectious
Toxic
Drug-induced
Post-traumatic

7. NBC Today Show Interview (1991) After Emergence of Post-traumatic Parkinsonism

8. Basal Ganglia

9. PD reflects Dopamine Insufficiency

12. Lewy body
Deposition of
a-synuclein

13. EPIDEMIOLOGY Parkinson’s Disease
Prevalence ~ 1,000,000
Annual incidence of about 50,000 – 60,000
Net prevalence increase of 15,000 patients annually
Average age of onset: 50 – 65 years old
85% of patients over age 65

14. EPIDEMIOLOGY Parkinson’s Disease
Peak age at onset = 60
2% lifetime risk, 4% if affected relative
850K in US
M:F = 3:2
Can live 20+ yrs with treatment
Incidence by Period
Olmstead Co., MN

15. ENVIRONMENTAL RISK FACTORS
Case-control studies show increased risk of PD with exposure to:
Herbicides, Pesticides
Living in a rural environment
Consumption of well water
Proximity to industrial plants or quarries
Smoking associated with lower risk

16. PARKINSON’S DISEASE Non-Motor Features
Cognitive Dysfunction
Depression
Hallucinations (late)
Autonomic dysfunction
Personality change
restricted vs. compulsive behavior

17. PARKINSON’S DISEASE Associated Features
Nigro-Striatal Pathway
Meso-limbic & Meso-cortical
Pathways
Hypomimia
Shuffling or festinating gait
Postural instability
Hypophonia
Dystonia
Dementia
Depression
Personality
Dermatitis
Constipation
Sensory deficits
Extra-CNS Structures

18. Adjusted for age, gender, education and psychomotor speed
Elgh et al., 2009

20. Symptomatic Treatment for PD
Replacement (Levodopa/Carbidopa) –
provide exogenous DA
most effective in relieving symptoms
use is typically delayed
may hasten emergence of diurnal fluctuations and dyskinesias
typically not prescribed until gait/postural problems arise or job is threatened
visual hallucinations, vivid dreams or nightmares occur in 20% of older patients

21. Motor fluctuations
Duration of levodopa benefit for motor symptoms decreases with disease progression
OFF
“Good” ON
without dyskinesia
“Bad” ON
with dyskinesia
Treatment-induced impairment

22. Treatment goal: Maximize Good ON time
OFF
“Good” ON
without dyskinesia
“Bad” ON
with dyskinesia

23. Mid-stage with moderate motor fluctuations
Early PD AM
midday
evening
C/L IR 25/100 1
Rasagiline 1mg
Mid-stage with moderate motor fluctuations
7AM
10AM
1PM
4PM
7PM
bedtime
C/L IR 25/100
1.5 1
C/L CR 50/200
Comtan 200mg
Pramipexole 0.5mg
Advanced with severe motor fluctuations
7AM
9AM
11AM
1PM
3PM
5PM
7PM
9PM
11PM
C/L IR 25/100 2 1
1.5
C/L CR 50/200
Comtan 200mg
0.5
Selegiline 5mg
Amantadine 100mg
Pahwa 2006 Neurology 66:983

24. ∙ changes the brain firing pattern but does not slow the progression of the neurodegeneration
∙ associated with reduction of sxs, so may enable reduction of medication
∙ can lead to a significant improvement in dyskinesias
∙ does not improve cognitive symptoms in PD and indeed may worsen them, so it is not generally used if there are signs of dementia. 

25. DBS clinical trial endpoint: Patient diaries