Idiopathic Parkinson's Disease Flashcards
mean age of onset
65
more common in males or females
males
aetiology
not fully understood, genetic and environemental factors
which form of PD is more likely to have a genetic component
early onset (<40)
what is the most prominent risk factor
age - prevalence increases sharply with age
what is the location of teh dopaminergic neurons that are affected
in the pars compacta of the substantia nigra of the basal ganglia
outline the pathophysiology
- 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
histology
Lewy bodies, these are eosinophilic alpha synculein inclusions
where are Lewy bodies found at the beginning and as disease progresses
initally in pars compacta of SN, they become more widespread as the disease progresses
which staging is used to classify pathology of PD and AD
Braak staging
when in the pathological timeline does the disease tend to present
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
which symtpoms develop first
prodromal premotor symptoms - around 7 years before motor symptoms
how many people get anosmia as part of teh premotor symptoms
90% - olfactory bulb is one of teh first structures to be affected
what is REM sleep behaviour disorder
vivid dreams and loss of normal muscle atonia during REM sleep - act out dreams
what other sleep related symptoms are seen
insomnia, sleep fragmentation, excessive daytime sleepiness
which autonomic features are seen
urinary urgency, hypotension
describe the pattern of body involvement of motor symptoms
almost always intially start on one side, eg arm, spread to ipsilateral leg, then finally to contralateral body
eventually involve axial muscles
describe the akinesia
- 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
what actions can pt perform to demonstrate akinesia
repeatedly oppose fingers/pronate and supinate arm
–> result is fatiguing and amplitude of movement decreases
which part of the movement is found to be the most difficult
- Initiating movement
- Rapid dexterous movements impaired causing difficulty writing (micrographia) and e.g. doing up buttons or zips
what happens to facial expression
facial immobility - gives a mask ike semblance of depression
what happens to blinking
rate decreases - serpentine stare
what happens to gait
decreased arm swing, small shuffling steps (festinating),
difficulty in first step or turning around - often freeze
how does posture change
becomes flexed and stooped
outline the progression of limb involvement in tremor
starts unilaterally in fingers, spreads to same leg and then opposite arm
when is the tremor present
at rest, stops when hand is in motion
how is the tremor classically described
pill rolling
what can exacerbate tremor
stress or emotion - like most tremors
how does rigidity rpesent
resistnace to passive movement around a joint - lead pipe
what is cogwheel rigidity
a combination of rigidty and tremor that can be felt during rapid supinationa nd pronation
what is the main danger with postural instability and balance disturbance
there is a greatly increased risk of falls - a late stage feature
this means that they may need assistance walking - impact QOL
what happens to speech
quiet, indistinct and flat
what changes happen to swallowing,and what problems does this cause
dysphagia - leads to drooling
diet chnages may be necessary
there is a risk of aspiration pneumonia
what is the most common psychiatric disorder assoicated
depression - due to disease impact and involvement of serotonin and adrenaline pathways
what cognitive and psychatric changes are seen and when
cognitive impairement, visual hallucinations, psychosis
late stage feature
what cognitive impairement can develop in late stage disease
Parkiinsons dementia
how do patients tend to first respond to treatment
dramatic improvement - honeymoon period
what is the aim of pharmacological treatment
to supplement depleted dopamine stores in the SN
what is the most effective drug in management
levodopa
when should you start levodopa
when symptoms start to impact QOL - due to honeymoon period?
describe how someone would respond to levodopa over time
- 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
what are teh long term effects of levodopa
- 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
is response ever lost to treatment
no
why would one use dopamine agonists first in younger patients
younger pt are more susceptible to levodopa induced motor fluccutations and dyskinesia - better to use D2 agonist first line if they have mild symtpoms
describe the mechansim of levodopa
it is a dopamine precursor that can cross the BBB and be convertef to dopamine in the CNS
why is levodopa used with carbidopa
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
how many times a day is levodopa initally given
3
describe the mechansim of dopamine agonists
act on the dopamine receptors directly - mimic dopamine
compare dopamine agonists to levodopa
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)
what is the use of MOAB inhibitors and COMT inhibitors
they prevent the brain and peripheral (respectively) breakdown of dopamine - can extend therapeutic benefit as an add on therapy or be used as monotherapy
which class of drugs shoudl someone with Parkinson’s avoid
anti dopaminergic - eg antipsychotics
which anti psychotic can be given if one is necessary
quietapine - very little D2 receptor activity
management of delirium in PD/LBD
quetiapine or lorazepam (short acting benzo, careful as can worsen delirium)
if an anti emetic is needed, which one is preferred
domperidone, doesnt cross the BBB to block Dopamine receptors in CTZ
how can motor complications be managed
increase dose frequency to challenge wearing ff
addition of COMT/MAOB to prolong action
slow release levodopa is available for overnight symptoms
