Week 9: Parkinson's disease Flashcards
What are the top 2 most common neurodegenerative conditions?
- Alzheimer’s
2. Parkinson’s
What is parkinsonism?
A clinical syndrome comprising of: -bradykinesia and at least one of: -tremor -rigidity -postural instability
What is the most common cause of parkinsonism?
parkinson’s disease
What are the specific clinical symptoms of PD?
- asymmetry of parkinsonism symptoms at onset
- sustained response to levodopa medication
What are the 4 causes of parkinsonism?
- Neurodegenerative conditions
- Drug-induced
- dopamine antagonists (anti-psychotics) - Vascular
- Metabolic
- Wilson’s disease
Which 3 neurodegenerative conditions make up the umbrella term ‘parkinson’s plus’?
- Dementia with lewy bodies
- Progressive supranuclear palsy
- Multiple system atrophy
What are the risk factors for idiopathic/sporadic PD?
- advancing age
- M>F ratio 3:2
- caucasians > asians and africans
- rural living and farmers -pesticides
- family history
Which lifestyle factors are said to decrease the risk of PD?
- tobacco
- coffee
- NSAID use
- alcohol consumption
Explain the two pathological hallmarks of PD
- Early degeneration and death of dopaminergic neurones within the substantia nigra pars compacta of the basal ganglia (lack of dopamine)
- Abnormal a-syn-lewy body protein and lewy neurite
Explain symptoms that might be present in the prodrome phase of PD
(before diagnosis)
- constipation
- RBD (REM sleep behaviour disorder)
- EDS (excessive daytime sleepiness)
- hyposmia - reduced sence of smell
- depression
What are the symptoms after diagnosis in order of progression?
- pain
- fatigue
- tremor
- rigidity
- anosmia
- bradykinesia
- urinary symptoms
- dementia
- dyskinesia
- dysphagia
- postural instability
- freezing of gait
- psychosis
How do we diagnose PD?
Diagnosis is made based on movement/motor symptoms and clinical examination:
- asymmetric signs
- bradykinesia plus at least one of: tremor, rigidity, postural instability
What is bradykinesia?
- slow and small movements with less rhythm
- slowed gait with shuffling steps
- reduced facial expression (hypomimia) and blinking
- reduced gesticulation
- small hand writing (micrographia)
What is freezing of gait?
- difficulty initiating movement
- slowed pace
- small steps
- sttooped, flexed posture
What are the features of the tremor in PD?
- in 70% of cases
- usually begins in one hand, then spreads bilaterally
- 4-7 Hz
How could we diagnose PD through imaging?
- CT, MRIs in PD are usually normal
- DaTscan - nuclear medicine sam - abnormal in PD but exposes patients to radiation and isn’t specific for PD
What is the gold standard medication for PD?
Levodopa (L-dopa): dopamine replacement –> increases dopaminergic stimulation of basal ganglia neurones
What drug is given to prevent levodopa being broken down before reaching the brain?
dopa decarboxylase inhibitor
What are the adverse effects of too much dopaminergic stimulation?
- dyskinesia
- dystonia/chorea
- confusion
- hallucinations
- impulse control disorders
What happens to the therapeutic window as PD progresses in a patient?
- therapeutic window narrows
- so patient will have more ‘off’ time when the medication isn’t working or is working too much (hyperkinetic)
What are 3 key features of neurodegenerative disorders?
- loss of neurones
- progressive
- irreversible
How is PD an ‘akinetic-rigid’ syndrome?
loss of voluntary movement, increased muscle tone
What is the most common cause of death associated to PD?
Bronchopneumonia
Which pathway is lost in PD?
Nigro-striatal inhibitory/excitatory pathway
Which drugs decrease dopamine breakdown?
MAO and COMT inhibitors
Why do we give L-DOPA as a combination therapy?
- usually, only 1% of L-DOPA would reach the brain, the rest would be metabolised in the intestines
- we overcome this by giving l-dopa with carbidopa which prevents breakdown of L-DOPA
What are some adverse effects of L-DOPA?
- ‘on-off’ effects –> worsening of PD symptoms
- nausea, vomiting, anorexia
- dyskinesias
- tachycardia
- hypotension
- insomnia, confusion
What does selegiline do?
prevents breakdown of dopamine
How is Huntington’s the mirror opposite of PD?
- it is a disorder of excessive and continual movement
- main symptoms are chorea and dementia
- starts at 30-50 typically
- juvenile onset more severe
what are the symptoms of Huntington’s?
- irritability
- moodiness
- antisocial behaviour
- fidgeting
- restlessness
- dementia
- gross choreiform movements
Why does a huntington patient find it difficult to stop movement?
- we’re loosing the inhibitory outputs from the striatum that project to the thalamus and back to the substantia nigra
- mutation in protein called huntingtin
- selective cell loss in cerebral cortex and corpus striatum
How is Huntington’s inherited and where is the gene defect?
- autosomal dominant
- gene defect on short arm of chromosome 4
- gives rise to an expanded and repeated CAG
