7 - Parkinson's Disease Flashcards
is tremor always present in PD?
no - absent in 30%
what genetic factors can result in PD?
- recessive genes - parkin
- dominant genes - SNCA
- dysfunction in cellular pathways
what are environmental factors that can result in PD?
- toxins - paraquat (herbicide commonly used in rural USA)
- ? spread of toxic/infective agents from gut/olfactory systems
what are the diagnostic criteria for PD?
- bradykinesia + tremor and/or rigidity
- absence of red flags
at least one of: - clear response to dopaminergic therapy
- levodopa-induced dyskinesia
- rest tremor
- olfactory loss
list 4 red flags for PD diagnosis
- symmetrical onset
- early gait abnormality and falls
- pyramidal tract signs
- poor levodopa response
- supranuclear gaze palsy
- early dementia
early gait abnormality, supranuclear gaze palsy, and early dementia would be red flags for PD - what may they be indicative of instead?
PSP - progressive supranuclear palsy
dysautonomia (disorder of involuntary functions), ataxia (disorders of coordination, balance and speech) and stridor (inspiration + expiration) are red flags for PD - what are they indicative of instead?
MSA - multiple system atrophy
apraxia (loss of ability to carry out skilled movement), myoclonus (twitching of muscles), alien limb (hand acts independently) are red flags for PD - what may they be indicative of instead?
CBS - corticobasal syndrome
what are possible pre-motor symptoms in PD?
- REM sleep behaviour disorder - act out dreams during night
- anosmia - loss of sense of smell
- constipation
- depression
- pain
what is the typical age of onset of PD?
- > 60
- young onset - (<40) in 5%
what is the mechanism of bradykinesia?
- increased inhibitory output to brainstem
- increased inhibitory output to thalamus and motor cortex
bradykinesia is associated with abnormal oscillations in basal ganglia circuits - what abnormal frequency is this?
20Hz
when is rigidity most obvious?
during slow movements
when is spasticity most obvious?
during velocity-dependent movements
what is the pathophysiology of rigidity in the periphery?
- reduced inhibition from type Ib fibres
- overactive type II fibres
- increased activity due to peripheral stimulation
what is the pathophysiolofy of rigidity in the central system?
- altered GABA and ACh activity in interneurons
- altered inhibition in indirect pathway
tremor is absent in roughly what % of PD pts?
30
is tremor more or less responsive to dopaminergic drugs?
less
where is tremor initiated? what brain region amplifies tremor activity?
initiated - basal ganglia
amplified - cerebellar-thalamo-cortical loops
what drugs are commonly used to treat tremor?
rasagiline
why isn’t dopamine given directly to treat PD?
it doesn’t pass the BBB - hence why it’s given as L-dopa
why are dopamine agonists less preferred than levodopa?
- more adverse effects
- impulse control disorders
- withdrawal problems
what are two motor complications in PD?
- wearing-off and motor functions
- L-dopa-induced dyskinesia
what are the mechanisms of motor complications in PD?
- there is pulsatile dopaminergic stimulation
- serotonin neurones try to compensate for lack of DA neurones
- not specialised for this = abnormal handling
- = abnormal synaptic plasticity
what are 4 impulse control disorders associated with PD?
- pathological gambling
- hypersexuality
- compulsive shopping
- binge eating
what are some risk factors for impulse control disorders related to PD?
- dopamine agonist use>levodopa
- smoking
- male
- young-onset PD
- depression
- family history of gambling or alcoholism
abrupt withdrawal of PD medications can result in what?
neuroleptic malignant syndrome
what is neuroleptic malignant syndrome?
- high fever
- stiffness of muscles
- altered mental state (paranoid behaviour)
- autonomic dysfunction (causes wide swings of BP, excessive sweating, excessive salivary production)
what are 2 later stage PD symptoms?
- axial symptoms
- dementia, psychosis
what are ‘axial’ symptoms in PD?
- falls, gait disturbance
- high risk of fractures
- dysphagia, speech disturbance
- generally poor levodopa response
what medications can help with dementia and psychosis related to PD?
rivastigmine
how do SPECT scans work?
single photons registered by rotating gamma camera
how do PET scans work?
two gamma-rays emitted at 180 degrees detected by static rings of detectors
what is the main difference between SPECT and PET scans?
SPECT - low cost, poor resolution, long tracer half life
PET - higher cost, better resolution
fluorodeoxyglucose is a measure of what?
marker of synaptic activity in the brain
fluorodopa binds to what in the brain?
bind to vesicles containing dopamine
