Idiopathic Parkinson's Disease

Question 1

mean age of onset

Answer 1

65

Question 2

more common in males or females

Answer 2

males

Question 3

aetiology

Answer 3

not fully understood, genetic and environemental factors

Question 4

which form of PD is more likely to have a genetic component

Answer 4

early onset (<40)

Question 5

what is the most prominent risk factor

Answer 5

age - prevalence increases sharply with age

Question 6

what is the location of teh dopaminergic neurons that are affected

Answer 6

in the pars compacta of the substantia nigra of the basal ganglia

Question 7

outline the pathophysiology

Answer 7

• progressive degeneration of dopaminergic neurons in PC of SN results in less dopamine being produced, other neurotransmitters are also affected, eg noradrenaline and ACh
• this affects teh output of the BG - overactive GABA from the globus pallidus internus (output nuclei) results in excessive inhibition
• there is decreased excitation of the motor cortex
• –> smooth, coordinated and controlled movement is not produced

Question 8

histology

Answer 8

Lewy bodies, these are eosinophilic alpha synculein inclusions

Question 9

where are Lewy bodies found at the beginning and as disease progresses

Answer 9

initally in pars compacta of SN, they become more widespread as the disease progresses

Question 10

which staging is used to classify pathology of PD and AD

Answer 10

Braak staging

Question 11

when in the pathological timeline does the disease tend to present

Answer 11

presents insidiously, usually the pathological process starts years before symptoms develop and at time of presentation often around 70% of Dopaminergic neurons are already lost

Question 12

which symtpoms develop first

Answer 12

prodromal premotor symptoms - around 7 years before motor symptoms

Question 13

how many people get anosmia as part of teh premotor symptoms

Answer 13

90% - olfactory bulb is one of teh first structures to be affected

Question 14

what is REM sleep behaviour disorder

Answer 14

vivid dreams and loss of normal muscle atonia during REM sleep - act out dreams

Question 15

what other sleep related symptoms are seen

Answer 15

insomnia, sleep fragmentation, excessive daytime sleepiness

Question 16

which autonomic features are seen

Answer 16

urinary urgency, hypotension

Question 17

describe the pattern of body involvement of motor symptoms

Answer 17

almost always intially start on one side, eg arm, spread to ipsilateral leg, then finally to contralateral body

eventually involve axial muscles

Question 18

describe the akinesia

Answer 18

• The cardinal clinical feature of Parkinsonism and is the main cause of disability
• Distinguished from other slowness of movement causes by a progressive fatiguing and decrement in the amplitude of repetitive movements

Question 19

what actions can pt perform to demonstrate akinesia

Answer 19

repeatedly oppose fingers/pronate and supinate arm

–> result is fatiguing and amplitude of movement decreases

Question 20

which part of the movement is found to be the most difficult

Answer 20

• Initiating movement
• Rapid dexterous movements impaired causing difficulty writing (micrographia) and e.g. doing up buttons or zips

Question 22

what happens to facial expression

Answer 22

facial immobility - gives a mask ike semblance of depression

Question 23

what happens to blinking

Answer 23

rate decreases - serpentine stare

Question 24

what happens to gait

Answer 24

decreased arm swing, small shuffling steps (festinating),

difficulty in first step or turning around - often freeze

Question 25

how does posture change

Answer 25

becomes flexed and stooped

Question 26

outline the progression of limb involvement in tremor

Answer 26

starts unilaterally in fingers, spreads to same leg and then opposite arm

Question 27

when is the tremor present

Answer 27

at rest, stops when hand is in motion

Question 28

how is the tremor classically described

Answer 28

pill rolling

Question 29

what can exacerbate tremor

Answer 29

stress or emotion - like most tremors

Question 30

how does rigidity rpesent

Answer 30

resistnace to passive movement around a joint - lead pipe

Question 31

what is cogwheel rigidity

Answer 31

a combination of rigidty and tremor that can be felt during rapid supinationa nd pronation

Question 32

what is the main danger with postural instability and balance disturbance

Answer 32

there is a greatly increased risk of falls - a late stage feature this means that they may need assistance walking - impact QOL

Question 33

what happens to speech

Answer 33

quiet, indistinct and flat

Question 34

what changes happen to swallowing,and what problems does this cause

Answer 34

dysphagia - leads to drooling diet chnages may be necessary there is a risk of aspiration pneumonia

Question 35

what is the most common psychiatric disorder assoicated

Answer 35

depression - due to disease impact and involvement of serotonin and adrenaline pathways

Question 36

what cognitive and psychatric changes are seen and when

Answer 36

cognitive impairement, visual hallucinations, psychosis late stage feature

Question 37

what cognitive impairement can develop in late stage disease

Answer 37

Parkiinsons dementia

Question 38

how do patients tend to first respond to treatment

Answer 38

dramatic improvement - honeymoon period

Question 39

what is the aim of pharmacological treatment

Answer 39

to supplement depleted dopamine stores in the SN

Question 40

what is the most effective drug in management

Answer 40

levodopa

Question 41

when should you start levodopa

Answer 41

when symptoms start to impact QOL - due to honeymoon period?

Question 42

describe how someone would respond to levodopa over time

Answer 42

* at first - dramatic positive response - honeymoon period * doses wear off - duration of effectiveness of each dose becomes shorter - pt may experience akinesia (not enough Dopamine) * eventually, on-off phenomenon - sudden unpredictable transitions between akinesia and dyskinesia (too much Dopamine * basically, disease progresses, medications become less effective and complications develop

Question 43

what are teh long term effects of levodopa

Answer 43

* Wearing off (motor fluctuations) – drug wears off and may experience akinesia/bradykinesia before next dose * Dyskinesia (overshoot – involuntary movements) reflects overstimulation of dopamine receptors à reduce dopaminergic supplementation * Impulsive and compulsive behaviour * Withdrawal symptoms if stopped suddenly (maybe because of impulsive/compulsive behaviour) – depression, anxiety, pain * Psychosis * Hallucinations

Question 44

is response ever lost to treatment

Answer 44

no

Question 45

why would one use dopamine agonists first in younger patients

Answer 45

younger pt are more susceptible to levodopa induced motor fluccutations and dyskinesia - better to use D2 agonist first line if they have mild symtpoms

Question 46

describe the mechansim of levodopa

Answer 46

it is a dopamine precursor that can cross the BBB and be convertef to dopamine in the CNS

Question 47

why is levodopa used with carbidopa

Answer 47

carbidopa prevents the peripheral conversion of levodopa to dopamine and thus reduces the side effects of peripheral circulating dopamine - nausea and vomiting this also means more of the drug acts in the CNS - greater efficacy

Question 48

how many times a day is levodopa initally given

Answer 48

3

Question 49

describe the mechansim of dopamine agonists

Answer 49

act on the dopamine receptors directly - mimic dopamine

Question 50

compare dopamine agonists to levodopa

Answer 50

they are elss well tolerated and generally give less good symptoms control however, they are assoicated with fewer motor complications in the long term (5 year period)

Question 51

what is the use of MOAB inhibitors and COMT inhibitors

Answer 51

they prevent the brain and peripheral (respectively) breakdown of dopamine - can extend therapeutic benefit as an add on therapy or be used as monotherapy

Question 52

which class of drugs shoudl someone with Parkinson's avoid

Answer 52

anti dopaminergic - eg antipsychotics

Question 53

which anti psychotic can be given if one is necessary

Answer 53

quietapine - very little D2 receptor activity

Question 54

management of delirium in PD/LBD

Answer 54

quetiapine or lorazepam (short acting benzo, careful as can worsen delirium)

Question 55

if an anti emetic is needed, which one is preferred

Answer 55

domperidone, doesnt cross the BBB to block Dopamine receptors in CTZ

Question 56

how can motor complications be managed

Answer 56

increase dose frequency to challenge wearing ff addition of COMT/MAOB to prolong action slow release levodopa is available for overnight symptoms