Parkinson’s Disease
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Case presentation
Definitions
Disease features
Pathology
Epidemiology
Treatments
George
•  58 y.o. successful architect in large firm
•  5/2010 –new onset tremor in right hand
•  handwriting has becoming smaller, less legible
•  10/2010- neurologic examination
•  right hand tremor at rest, can control, but returns when
distracted
•  slowed movements on right
•  muscle rigidity R > L
George
•  Reports ↑ problems since late 2009
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lost client due to failure to pick up errors
taking much more time to complete routine tasks
referrals have dropped off substantially
partner in firm suggesting he go on disability
fatigued – leaving work early, going to bed before 9PM
forgetting to pay bills at home
yard work taking more time due to slowed movement
PARKINSONISM
(‘pill-rolling’)
(slowed movement)
(‘lead-pipe’ or ‘cog-wheel’)
Clinical Features: Secondary motor
symptoms
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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
Clinical Features: Non-motor symptoms
Early
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loss of sense of smell
constipation
REM behavior disorder
mood disorders
orthostatic hypotension
Later
•  sleep disturbances
•  incontinence
•  sexual problems
•  excessive saliva
•  weight loss or gain
•  fatigue
•  Cognitive impairment
•  memory difficulties, slowed thinking,
confusion, dementia
•  Psychiatric
•  Depression, anxiety
Parkinsonian Syndromes
•  Idiopathic
•  Parkinson’s Disease
•  Symptomatic
•  Infectious
(‘Awakenings’)
•  Toxic (Manganese, CO,
MPTP)
•  Drug-induced
(neuroleptics)
•  Post-traumatic (boxers)
PD Motor Difficulties off-meds
NBC Today Show Interview (1991)
After Emergence of Post-traumatic Parkinsonism
Basal Ganglia
PD reflects Dopamine Insufficiency
Lewy body
Deposition of
a-synuclein
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
•  Rare juvenile onset
EPIDEMIOLOGY
Parkinson’s Disease
•  Peak age at onset = 60
•  2% lifetime risk, 4% if
affected relative
•  850K in US
•  M:F = 3:2
•  Highest rate in Hispanics,
lowest in African Americans
•  Can live 20+ yrs with
treatment
Incidence by Period
Olmstead Co., MN
GENETIC FACTORS IN PD
•  Twin Studies
•  Similar MZ – DZ concordance in 193 twin pairs
•  In 16 twin pairs with early PD (< age 50), concordance was
4/4 MZ pairs & 2/12 DZ pairs, suggesting strong genetic
contribution to early onset cases
•  Family Studies
•  Southern Italian family
•  ~ 10% have autosomal-dominant, autopsy-proven PD
•  Single base substitution on chromosome 4 at the gene that
codes for alpha-synuclein protein.
•  High levels of alpha-synuclein aggregates found in Lewy
bodies
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
MPTP Model of PD
•  Parkinsonism seen in drug addicts exposed to
synthetic heroin (MPTP) (cf ‘Awakening the Frozen
Addicts’, 1993 BBC special on Youtube)
•  Progressed over several weeks and improved
modestly with dopamine replacement therapy
•  No other neuronal involvement (‘pure
parkinsonism’)
•  MPTP in primates induces parkinsonism and
selective degeneration of nigro-striatal DA neurons
•  Chemical resemblance to some herbicides and
pesticides suggests possible toxic etiology of PD
via oxidative stress/other mechanisms
PARKINSON’S DISEASE
Non-Motor Features
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Cognitive Dysfunction
Depression
Hallucinations (late)
Autonomic dysfunction
Personality change
•  restricted vs.
compulsive behavior
PARKINSON’S DISEASE
Associated Features
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Nigro-Striatal Pathway
Meso-limbic & Meso-cortical
Pathways
Hypomimia (masked facies)
•  Dementia
Shuffling or festinating gait
•  Depression
(stooped posture,
•  Personality
imbalance, short steps)
Postural instability (easily
Extra-CNS Structures
pulled off balance)
•  Dermatitis
Hypophonia (soft voice)
•  Constipation
Dystonia (painful muscle
•  Sensory deficits
contractions)
Neuropsychological Profile in Early PD
(Elgh et al., 2009)
•  Community-based (geographically-based
referral center)
•  Only included patients who met PD criteria
one year after initial baseline exam
•  Comprehensive neuropsych exam within 1-2
mos of prior to initiation of medications
•  Compared performances to age & gender
matched controls (controls better educated)
Adjusted for age,
gender, education
and psychomotor
speed
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 (‘off-on’, ‘wearing
off’ periods) 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
∙ 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. George’s Results
WAIS-III
WMS-III
CVLT
SS
SS
Similarities
15
Rey – Figure Copy
1
Block Design
10
Trail Making A
5
Letter-Num Seq.
13
Trail Making B
7
Digit Symbol
6
Phonemic Fluency
3
Imm. Memory
10
Category Fluency
12
Delayed Memory
9
Grooved Pegboard
4
Initial Learning
7
WCST Errors
3
Long Delay Free Recall
16
Categories
5
Impressions/Recommendations
•  Clinically significant weaknesses in processing speed and
executive function
•  Consistent with impairments in multiple domains in earlyonset PD
•  Sufficient to explain his work and ADL deficits
•  Recommendations
•  Eligible for disability under current policy
•  Cognitive rehab. focused on executive dysfunction
•  Part-time consulting to exploit his wealth of knowledge
George’s Results
WAIS-III
WMS-III
CVLT
Base
line
Base
line
3 yrs
3 yrs
Similarities
15
14
Rey – Figure Copy
1
n/a
Block Design
10
5
Trail Making A
5
3
Letter-Num Seq.
13
7
Trail Making B
7
2
Digit Symbol
6
4
Phonemic Fluency
3
2
Imm. Memory
10
9
Category Fluency
12
6
Delayed Memory
9
5
Grooved Pegboard
4
3
Initial Learning
7
5
WCST Errors
3
1
Long Delay Free Recall
16
9
Categories
5
1