Parkinson's Flashcards
what type of movement disorder is Parkinson’s?
akinetic rigid syndrome
types of parkinson’s related disease
drug induced parkinsonism
Parkinson’s disease
Parkinson’s plus disease
what are the cardinal features of parkinson’s?
rest tremor - disappears on movement
rigidity
bradykinesia - slow movements
postural instability
pathophysiology of parkinson’s
diminished/ loss of dopaminergic neurones in substantia nigra
lewi bodies form in brain - substantia nigra
downward movement control is lost as less dopamine is produced by dopaminergic neurones of substantia nigra
imaging for Parkinson’s
DaTscan
DaTscan findings
asymmetric
loss of tail on substantia nigra dopamine
minimal dopamine secretion
diagnosis of parkinson’s
clinical features
exclude other syndromes
DaT scan
trial L-dopa or apomorphine to see if it helps
apomorphine
quicker effect than L-dopa
How does L dopa work?
replaces what is lost
treatments for parkinson’s
Levodopa
dopamine agonists
surgery
dopamine agonists e.g.
apomorphine
risk of dopamine agonists
can cause dopamine dysregulation syndrome
changes behaviour
hypersexuality
gabbling addiction
levodopa
becomes less effective as disease progresses
resistance develops
symptoms then worsen
therapeutic zone can be very specific
too much levodopa
dyskinesia
surgery for parkinson’s
destructive lesion
chronic stimulation
reconstruction of lost circuitry
destructive lesions
create lesion in brain to treat the parkinson’s symptoms
use injections or gamma-knife
lesion in basal ganglia
chronic stimulation
electrode inserted into areas of the brain
deep brain stimulation into subthalamic nucleus
what are the risks of chronic stimulation/ deep brain stimulation
risk of temporary blindness due to proximity of optic nerve
risk of damage to swallowing areas
to avoid these risks electrodes are inserted while patient awake
reconstruction of host circuitry
stem cell transplant
differentiation into dopaminergic neurones
insert into basal ganglia
what drugs can cause parkinsonism?
antiemetics
antipsychotics
antiemetics that cause parkinsonism
cyclizine
metoclopramide
antipsychotics that cause parkinsonism
haloperidol
clozapine
deplete dopamine
what is parkinson’s plus syndrome?
parkinson’s features as well as additional features
examples of parkinson’s plus syndromes
PSP
MSA
Wilson’s disease
CBD
PSP
progressive supranuclear palsy
PSP
parkinsonism supranuclear gaze palsy pseudobulbar palsy dystonic rigidity of neck and trunk dysarthria dementia poor response to L dopa midbrain degeneration
supranuclear gaze palsy
unable to look up or down voluntarily
pseudobulbar palsy
very extreme mood swing type behaviour
MSA
multiple system atrophy
multiple system atrophy symptoms
parkinsonism autonomic failure cerebellar degeneration - poor balance pyramidal signs - spastic paraparesis and weakness sighs for no reason sleep apnoea
multiple system atrophy pathogenesis
area affected around pons
relay of all tracts is the area affected
hot cross bun appearance on MRI of midbrain
treatment for MSA
no response to L dopa treatments often unlikely to be beneficial anticholinergics BP support elastic stockings bed head up fludrocortisone
mean age of onset of PD?
45-60
0.5-1% of over 60s
2nd most common neurodegenerative disease
risk factors for PD?
genetics pesticides/ herbicides pollution age men more at risk drugs
symptoms of PD?
tremor at rest - 4-7Hz rigidity bradykinesia bilateral signs no sensory loss power is normal shuffling steps gait stooped gait with reduce arm swinging and narrow base slow, monotonous and slurred speech plain face/ facial stare reduced blinking rate depression dementia hallucinations greasy and sweaty skin heartburn dribbling dysphagia weight loss constipation
investigations/ diagnosis
clinical MRI will be normal dopamine transporter imaging = unreliable and expensive handwriting anosmia violent dreams no lab tests DaT scan trial of levodopa/ apomorphine
lewy bodies
can be seen throughout the brain
often cause co-existing dementia
dopamine and ACh in PD
dopamine is normally inhibitory at corpus striatum
normally dopamine inhibits ACh release in corpus striatum but in Parkinson’s too much ACh is released
there is cell death by excitotoxcity, oxidative stress and apoptosis
progression of PD
no remission
usual course = 10-15 years
doesn’t directly cause death
puts strain on the body, increasing susceptibility to infection
progression is unique to each person and rate of progression is variable
what is the main cause of death in PD?
bronchopneumonia as a result of dysphagia
how many stages of PD are there?
1 - mild symptoms 2 - worsening symptoms 3 - mid-stage 4 - severe and limiting symptoms 5 - advanced and debilitating
stage 1 of PD
tremor and unilateral movement symptoms
changes in posture, walking and facial expressions
stage 2 of PD
tremor rigidity bilateral movement symptoms walking problems poor posture able to live alone but daily tasks are challenging
stage 3 of PD
loss of balance
bradykinesia
falls more common
impaired daily activities
stage 4of PS
able to stand unassisted but walked required
need support with daily activities and unable to live alone
stage 5 of PD
unable to stand or walk due to stiffness wheelchair needed or bed ridden constant nursing required hallucinations and delusions motor and non-motor symptoms
rating PD scales
Hoehn and yahr stages
unified parkinson’s disease rating scale
Hoehn and yahr stages
monitor motor symptoms and progression
Unified parkinson’s disease rating scale
accounts for motor and non-motor symptoms, mental functioning, mood and social interaction
accounts for cognitive difficulties, ability to carry out daily activities and treatment complications
other causes of Parkinsonism/ differentials
alzheimers multi-infarct dementia repeated head injury drugs vascular events, orthostatic hypotension with atonic bladder, dementia, wilson's disease, apraxic gait parkinson's plus syndrome multi-system atrophy progressive supranuclear palsy
what drugs can cause parkinsonism?
neuroleptics
dopamine reducing drugs - dopamine antagonists
what are the treatments for PD?
Dopamine agonists
L-dopa
drugs that release dopamine
MAO-B inhibitors
Dopamine agonists mechanism of action
bind to dopamine receptors and mimic the effects of dopamine
L dopa mechanism of action
dopamine precursor so increases the amount of dopamine in CNS - can cross BBB
MAO-B inhibitors
selective inhibition of monoamine oxidase B which metabolises dopamine
therefore increasing dopamine levels in the brain
L-dopa downsides
efficacy decreases over time
on-off effect
side effects of L-dopa
nausea GI upset dyskinesia - unwanted movements psychosis impulse control disorders hypotension arrhythmia confusion disorientation insomnia nightmares
impulse control disorders
compulsive eating compulsive shopping hypersexuality punding pathological gambling
side effects of MAO-B inhibitors
postural hypotension
atrial fibrillation
can be very serious
anticholinergic side effects
dry mouth dizziness urinary retention anxiety confusion tachycardia hallucinations insomnia memory problems
contraindications for anticholinergics
urinary retention
acute glaucoma
GI obstruction
prostate problems
psychological effects of PD
depression and anxiety are most common hallucinations memory problems dementia psychosis delusions impulse control disorders apathy sleep disorders panic attacks lonliness
what is apathy?
diminished motivation and goal directed behaviour
progressive supranuclear palsy symptoms
falls balance problems paralysis vertical gaze parkinsonism cognitive impairment progressive and varying course
age of onset of progressive supranuclear palsy
60-65
7 years survival on average
treatment for progressive supranuclear palsy
poorly responds to L-dopa
symptoms of multi-system atrophy
parkinsonism cerebellar problems autonomic problems - postural hypotension akinesia rigidity
treatment for multi-system atrophy
responds poorly to L-dopa
what is multi-system atrophy?
degenerative neurological disorder
symptoms of Wilson’s disease
parkinsonism liver failure renal failure wide neurological problems parkinsonism chorea akinesia tremors rigidity personality and behavioural problems cognitive impairment
Wilson’s disease age of onset
6-20
treatment of wilson’s disease
Penicillamine
treat early and can be very well controlled
pathogenesis of wilson’s disease
autosomal recessive condition
causes problems with copper metabolism so copper is deposited in the liver, basal ganglia, cornea and kidneys
what happens to the direct and indirect pathways in PD?
loss of activation of direct and loss of inhibition of indirect pathways
