Parkinson's Disease

Front 1

Dr. James Parkinson first described Parkinson's in 1817 in this essay

Back 1

An Essay on the Shaking Palsy

Front 2

Mean age of onset for PD between ___-___ years

Back 2

58-62 years

Front 3

- Bradykinesia/Akinesia
- Resting Tremor
- Rigidity or increased "stiffness"
- Postural instability
- Dystonia

Back 3

Cardinal Motor Signs of parkinsonism

Front 4

Area of the brain involved in self-initiated movements
- when not enough activation, people have difficulty initiating voluntary movement and have to use other ares of their brain --> prefrontal area (executive functioning - thinking about what they want to do so they can activate SMA--> Premotor Area)
- Very fatiguing because everything is an effort

Back 4

Supplementary Motor Area

Front 5

Slowness of movement; inability to initiate adn execute a movement; "freezing" episodes

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Bradykinesia/Akinesia

Front 6

Affects proximal musculature early, with spread to muscles of face and extremities
- Types: Cogwheel, Leadpipe
- Leads to decreased ROM, slowness, and fatigue
- no trunk movement during gait
- "en bloc" - no dissociation between LE and trunk
- reduced ability to turn/rotate trunk

Back 6

Muscle Rigidity

Front 7

jerky, ratchetlike resistance to passive movement as muscles alternately tense and relax

Back 7

Cogwheel Rigidity

Front 8

Constant, uniform resistance to passive movement

Back 8

Leadpipe Rigidity

Front 9

Slowness and difficulty maintaining voluntary movement
- impaired ability to initiate and execute a movement (akinesia)
- slowness and reduction in movements lead to prolonged time to complete ADLs
- May experience "freezing" episodes
- Reflex movements may be impaired (eg. blinking and facial movements) so that they require concentrated volitional effort = "masked expression"

Back 9

Bradykinesia

Front 10

Present in 70% at initial dx
- usually begins unilaterally, affecting hand and UE
- Slow (4-7 Hz), pill-rolling
- Generally disappears with action or intention and sleep
- Stress and anxiety increase it

Back 10

Resting Tremor

Front 11

Loss of balance or lack of recovery of balance when perturbed
- respond to instability with abnormal muscle coactivation patterns
- difficulty with feed-forward postural control
- some pt's with PD have an abnormal gait with retropulsion, leading to backward falls
- rapid, festinating gait in combination with a stooped posture leads to forward falls

Back 11

Postural Instability

Front 12

- Fatigue
- Shuffling gait with decreased arm swing
- Decreased facial expression
- Muscle aches or cramps
- soft voice with poor annunciation
- Decreased hand dexterity
- Micrographia (smaller writing)
- Dysphagia
- Depression
- Feelings of fear and anxiety
- Memory problems
- confusion/dementia
- sialorrhea
- sleep disturbances (life-like nightmares)
- urinary problems
- constipation
- sexual dysfunction

Back 12

S/S of PD

Front 13

Idiopathic PD = 78% of all parkinsonism cases

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Primary Parkinsonism

Front 14

- Brain injur from strokes, toxins, trauma (boxing), infections (encephalitis, HIV), metabolic abnormalities (hypo- or hyper-thyroidism or parathyroidism, liver failure), drug-induced

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Secondary Parkinsonism

Front 15

- Progressive Supranuclear Palsy
- Multiple System Atrophy
- Corticobasalganglionic Degeneration

Back 15

Parkinson-Plus Syndromes

Front 16

Loss of balance or lack of recovery of balance when perturbed
- respond to instability with abnormal muscle coactivation patterns
- difficulty with feed-forward postural control
- some pt's with PD have an abnormal gait with retropulsion, leading to backward falls
- rapid, festinating gait in combination with a stooped posture leads to forward falls

Back 16

Postural Instability

Front 17

- Fatigue
- Shuffling gait with decreased arm swing
- Decreased facial expression
- Muscle aches or cramps
- soft voice with poor annunciation
- Decreased hand dexterity
- Micrographia (smaller writing)
- Dysphagia
- Depression
- Feelings of fear and anxiety
- Memory problems
- confusion/dementia
- sialorrhea
- sleep disturbances (life-like nightmares)
- urinary problems
- constipation
- sexual dysfunction

Back 17

S/S of PD

Front 18

Idiopathic PD = 78% of all parkinsonism cases

Back 18

Primary Parkinsonism

Front 19

- Brain injur from strokes, toxins, trauma (boxing), infections (encephalitis, HIV), metabolic abnormalities (hypo- or hyper-thyroidism or parathyroidism, liver failure), drug-induced

Back 19

Secondary Parkinsonism

Front 20

- Progressive Supranuclear Palsy
- Multiple System Atrophy
- Corticobasalganglionic Degeneration

Back 20

Parkinson-Plus Syndromes

Front 21

- Most common of hte Parkinson-plus syndromes
- Damage in basal ganglia, brainstem, thalamus, and frontal cortex
- Sx include: postural instability leading to falls within first year of disease onset, supranuclear opthalmoplegia (vertical gaze paresis, especially in the downward direction)
- Prognosis - 9.7 year median survival from onset of sx

Back 21

Progressive Supranuclear Palsy (PSP)

Front 22

- postural instability leading to falls within the first year of disease onset
- supranuclear opthalmoplegia - vertical gaze paresis, especially in the downward direction

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Sx of Progressive Supranuclear Palsy (PSP)

Front 23

- Progressive, idiopathic degenerative process begining in adulthood
- Sx: varying degress of parkinsonism, autonomic failure, cerebellar dysfunction, and pyramidal signs (UMN, corticospinal)
- Poorly responsive to levadopa or dopamine agonists
- orthostatic hypotension develops in 66% of pts
- prognosis: median survival in one study was 6.2 years with a range of 0.5-24 years

Back 23

Multiple System Atrophy (MSA)

Front 24

Varying degrees of parkinsonism, cerebellar dysfunction, autonomic failure, pyramidal signs, orthostatic hypotension, festination of speech

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Sx of Multiple System Atrophy (MSA)

Front 25

- Cortical atrophy of the frontal and parietal lobes and loss of dopamine in the substantia nigra
- Sx: focal rigidity, bradykinesia, tremor, marked dystonia (usually in one arm), often have limb apraxia
- Prognosis - severe disability and death within 10 years

Back 25

Corticobasalganglionic Degeneration (CBGD)

Front 26

Focal rigidity, bradykinesia, tremor, marked dystonia (usually in one arm), limb apraxia

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Sx of Corticobasalganglionic Degeneration (CBGD)

Front 27

Can't produce a movment upon request (motor planning)

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Apraxia

Front 28

- Begins slowly, usually on one side of the body and then involves the other side
- Slow, variable rate of progression, lasting between 20-30 years after onset
- May have normal lifespan because it begins so late in life and progresses slowly
- Progression of disability assessed using: Hoehn and Yahr Classification of Disability and/or United Parkinson Disease Rating Scale (UPDRS)

Back 28

Clinical Course for Idiopathic Parkinson's Disease

Front 29

Five stages within Stage 1 indicating minimal disease involvement to Stage 5, indicating severe involvement

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Hoehn and Yahr Classification of Disability (for PD)

Front 30

Contains: 1) Mentation, Behavior, and Mood, 2) ADL and 3) Motor scales

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United Parkinson Disease Rating Scale (UPDRS)

Front 31

- Postural Instability Gait Disturbed (PIGD)
- Tremor Predominant
- Early Frontal Dementia with Bradykinesia and Rigidty

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Variants of Primary PD

Front 32

Dominant sx include postural instability and gait disturbance

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Postural Instability Gait Disturbed (PIGD)

Front 33

Tremor is the main sx; few problems with bradykinesia or postural instability

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Tremor Predominant PD

Front 34

PD Pathology
- Disease affects melanin-containing monoamine neurons of the brain, particularly the dopamine neurons in the ______ of the brainstem
- Results in decreased dopamine levels in other parts of the basal ganglia with immportant motor functions (putamen and caudate = striatum)

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substatia nigra pars compacta (SNpc)

Front 35

- a pathologic hallmark of PD
- round, intracytoplasmic inclusions consisting mainly of misfolded alpha-synuclein protein found in monoamine neurons
- found in abnormally increased amount

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Lewy Bodies

Front 36

Dopamine is excitatory - selects movements you want to do

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Direct Pathway (D1)

Front 37

Dopamine is inhibitory - stops movements you don't want to do

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Indirect Pathway (D2)

Front 38

- Sporadic PD
- Familial PD
- Environmental
- Combination of Cellular Mechanisms

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Etiology of Primary PD

Front 39

- Experimental model for production of Parkinsonism in animals. ____ is structurally similar to certain pesticides
- Metabolism of ____ in astrocytes and metabolite is taken up by dopaminergic neuron mitocondria.
- Metabolite inhibits complex I (NADH-CoQ1) fo the mitochondrial respiratory chain --> ATP production falls --> cell death

Back 39

MPTP - Environmental Toxin model

Front 40

- At least 2 out of 4 cardinal sx: resting tremor, bradykinesia, rigidity, postural instability
- Absence of secondary causes (drugs, metabolic, etc)
CT scan or MRI used to r/o other disorders
- Definitive only at autopsy

Back 40

Diagnosis of PD

Front 41

According to Honolulu-Asia aging study
- Olfactory deficits
- Obesity
- Constipation
- Slow Reaction Times

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factors associated with getting PD or having Lewy Bodies in brain were midlife:

Front 42

Mean survival after onset of PD is ____ years
- longer in non-demented PD (tremor predominant are at less risk for dementia than PIGD)
- Longer with L-dopa use, especially if drug started early in disease

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15 years

Front 43

- Older age at onset (>57 yrs)
- Rigidity/hypokinesia as presenting sx
- PIGD

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Worse prognosis in PD

Front 44

- Resting tremor
- Bradykinesia
- Rigidity
- Postural Instability

Back 44

4 Cardinal Sx of PD

Front 45

Pulmonary complications, UTIs, complications of falls and fractures

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Most common cause of death in PD

Front 46

_____ drugs improve motor funciton, reduce both the morbidity and mortality of PD, and improve quality of life

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Dopaminergic Drugs

Front 47

- First developed in the 1960s; most clinically effective drug for the Sx of PD
- Still the "gold standard" for PD medications

Back 47

Levadopa

Front 48

Combination of levadopa and carbidopa that crosses the BBB
- turned into dopamine within the nerve cell
- alleviates bradykinesias and rigidity with less effect on tremor

Back 48

Sinemet

Front 49

Orhtostatic hypotension, dyskinesias, hallucinations, sleepiness

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Side Effects of Sinemet/Levodopa

Front 50

- Action - directly stimulate dopamine receptors
- Brands - Mirapex (pramipexole), Requip (ropinirole), Upima (apomorpine)

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Dopamine Agonists

Front 51

- Actions - potentiate levadopa; prevent degredation by COMT
- Brands - Comtan (Entacapone), Stalevo (Levadopa and Entacapone), Tasmar (tolcapone)

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COMT Inhibitors

Front 52

-Actions- reduce overactivity of ACh; inhibit DA reuptake in striatum - good for tremors
- Brands - Artane (trihexyphenidyl HCl), Cogentin (benztropine mesylate), Kemadrin (procyclidine hydrocloride)

Back 52

Anticholinergics

Front 53

Action - Inhibits MAO-B that degrades DA
- often used earlier; neuroprotective effect
- Brands - Eldepryl (selegiline hydrochloride), Azilect (rasagiline)

Back 53

Selegiline/Rasagiline

Front 54

- Action - releases DA; decreases DA reuptake; DA agonist
- Brands - Symmetrel (amantadine hydrochloride)

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amantadine

Front 55

- Shorter tx horizon; lower risk of long-term complicatoins; comorbidities
- Levadopa well tolerate; effective; sedating adjunctive medications avoided
- some DA-agonist drugs aren't well tolerated in this population

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Initial Therapy for the Elderly PD patient

Front 56

- Long-term tx horizon; increased risk of long-term complications
- Levadopa-sparing/neuroprotective strategies (eg. selegiline, DA agonists)

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Initial Therapy in the Young PD patient

Front 57

Surgery permanently destroys overactive globus pallidus internus (GPi) to eliminate rigidity and significantly reduce contralateral tremor, bradykinesia, and balance problems

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Pallidotomy

Front 58

Destroys part of the VL thalamic nucleus to relieve contralateral tremors

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Thalamotomy

Front 59

- Many pts experience reduction of their PD sx (tremors, rigidity, bradykinesias, dyskinesias) and can greatly reduce their medications
- reduction in meds leads to significant improvement in side effects such as dyskinesias

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Benefits of Deep Brain Stimulation (DBS)

Front 60

- Most pts must still take medications
- amoutn of reduction in sx varies
- non-motor sx (gait and balance) of PD not affected - still have issues with postural instability

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Limitations of Deep Brain Stimulation (DBS)

Front 61

Grafting of fetal cells or autotransplantaiton with the pt's own adrenal medullary cells to replace the dopamine-producing cells inthe substantia nigra. Remans controversial
- mixed results - some benefited, others worse

Back 61

Fetal Cell Transplantation

Front 62

Research to try to make human embryonic stem cells into dopamine-producing neurons that can be used to tx PD

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Stem Cell Research