Parkinson’s Disease Flashcards
What is the difference between incidence and prevalence?
Prevalence:
- how many people there are with a condition at a given time
Incidence:
- probability of occurrence of a particular medical condition
Why is the prevalence of people with Parkinson’s disease higher than the incidence?
People with Parkinson’s tend to live for a long time
Prevalance and incidence are increasing as the population is getting older
What is the definition of Parkinsonism?
A clinical syndrome comprising:
Bradykinesia
and at least one of:
- Tremor
- Rigidity
- Postural instability
What is bradykinesia?
Slowness of movement
What is the definition of Parkinson’s disease?
- The most common cause of Parkinsonism
- it is due to specific pathology in the brainstem and basal ganglia - Lewy bodies and neuronal degeneration
- it involves certain clinical features - asymmetry, sustained response to levodopa etc.
Why is it important to know the clinical features of Parkinson’s disease?
Certain clinical features at the time of diagnosis help to distinguish from other causes of Parkinsonism
What are the 4 categories of causes of Parkinsonism?
- Neurodegenerative conditions
- Drug-induced
- Vascular
- Metabolic
What neurodegenerative conditions can cause parkinsonism?
What is a term for these conditions?
- Parkinson’s disease (PD)
- dementia with Lewy bodies (DLB)
- progressive supranuclear palsy (PSP)
- multiple system atrophy (MSA)
The bottom three conditions are known as Parkinson’s Plus
They all have the features of Parkinsonism but the processes that happen in the brain and the rapidity of decline is faster than PD
What can cause drug-induced parkinsonism?
Parkinsonism is caused by a lack of available dopamine
this can occur due to degeneration of neurones or dopamine-blocking drugs
these are dopamine agonists (anti-psychotics, anti-emetics)
What are the vascular causes of parkinsonism?
Tiny blood vessels around the basal ganglia being damaged can induce parkinsonism
What is the main metabolic cause of parkinsonism?
Wilson’s disease
What are the risk factors for Parkinson’s disease?
Advancing age:
- 1% 60 years, 4% 80 years
- 5% cases are diagnosed < 40 years old
- male > female 3:2
- caucasians > Asians and africans
- rural living and farmers
- family history
What environmental risk factors lead to increased risk of Parkinson’s disease?
- Pesticide exposure
- prior head injury
- rural living
- beta-blocker use
- agricultural occupation
- well water drinking
What are the environmental risk factors that decrease risk of Parkinson’s disease?
- Tobacco smoking
- coffee drinking
- NSAID use
- calcium channel blocker use
- alcohol consumption
Why may calcium blockers decrease risk of Parkinson’s disease?
Substantia nigra cells exposed to increased calcium ion flux because of maintained autonomous electrical activity
What are the 2 pathological hallmarks of Parkinson’s disease?
- Early degeneration and death of dopaminergic neurones within the substantia nigra pars compacta of the basal ganglia
- a-syn - Lewy body (cell body) and Lewy neurite (axons)
This is the accumulation of abnormal protein that is wrapped in Lewy body
What is the abnormal protein that accumulates in Parkinson’s disease?
A - synuclein protein
this is a soluble protein that becomes insoluble and triggers a cascade of reactions that leads to the death of the dopamine releasing neurones
What is meant by “prodrome”?
Period before diagnosis
changes in the brain are happening but the patient hasn’t yet development movement symptoms
What are examples of things which may occur during the prodrome phase?
This can go back to 20 years prior to diagnosis or more
includes constipation, REM sleep behaviour disorder, lack of sense of smell and being tired during the day
What is meant by the “easy” stage of Parkinson’s disease?
The first 10 years after diagnosis
drugs can be used to replace dopamine that will treat both the motor and non-motor symptoms during this period
What is meant by the “hard” stage of Parkinson’s disease?
The more complicated symptoms of Parkinson’s start to arise
- psychosis and hallucinations
- dementia
- swallowing problems
- problems with blood pressure control
60-70% of dopamine cells are lost before the tremor and stiffness of movement arises
How is the progression of Parkinson’s disease linked to pathology?
The a-synuclein protein deposition begins in the bottom part of the brain (medulla)
the deposition then progressively moves up the brainstem and through the brain over time
the protein deposition may originate outside of the brain altogether, explaining the symptoms in the prodromal phase
What prodromal symptoms may be explained by the deposition of a-synuclein protein around the body?
- Abnormal protein deposition in the gut may cause constipation
- it may be deposited around the vagus nerve in the heart to cause cardiac symptoms
- deposition around the olfactory bulb leads to loss of sense of smell
- nuclei that secrete noradrenaline and serotonin may be infiltrated, leading to depression
After diagnosis (blue line), deposition of a-synuclein protein causes what types of symptoms?
Deposition in the frontal lobe leads to mild cognitive impairment
Deposition in the parietal and occipital lobes leads to dementia and hallucinations
What are the non-motor features associated with Parkinson’s disease?
- Anosmia
- sleep disturbance
- depression and anxiety
- cognitive issues - mild cognitive impairment and dementia
- psychotic symptoms - visual hallucinations and delusions
- constiaption
- urine issues - hyperexcitability
- postural hypertension
- pain
What is anosmia?
Lack of sense of smell
What types of sleep disturbances are seen in Parkinson’s disease?
Excessive sleep
or
REM sleep behaviour disorder
How is a clinical diagnosis of Parkinson’s disease made?
Diagnosis is made based on movement / motor symptoms and based on clinical examination
asymmetric signs (often one sided to begin with) at onset
look for bradykinesia plus at least one of:
- tremor
- rigidity
- postural instability
How do you often test for bradykinesia?
Ask the patient to finger tap
watch how fast they are able to do this, whether they slow down, what the rhythm is like etc.
What signs may be indicative of bradykinesia?
Slow and small movements with less rhythm:
- slowed gait with shuffling steps
- reduced facial expression and blinking
- reduced gesticulation (use of gestures)
- small handwriting
usually notice a reduced arm swing when walking on one side
What is the problem with the method of making a clinical diagnosis of Parkinson’s disease?
Diagnosis is based on movement even though it is a whole body disorder
Late to make the diagnosis as many other changes have been occurring over time
What changes in gait may be observed in a patient with Parkinson’s disease?
- Difficulty initiating
- slowed pace
- small steps
- stooped flexed posture
- ‘festinating’
- several steps needed to turn
- reduced arm swing
- freezing
What is hypomimia?
Reduced facial expression
this is through lack of facial movement due to slowness in Parkinson’s patients
What is micrographia?
What is the tremor like in a Parkinson’s patient?
How many patients have a tremor?
70% of people with PD have a tremor
it usually begins in one hand and then spreads bilaterally
it is a rest tremor (worse at rest)
it has 4-6 Hz frequency
leg and jaw tremors are also seen
What types of rigidity are present in Parkinson’s disease?
- Stiffness
- “lead-pipe” rigidity - the stiffness is throughout the patient’s range of movement
- “cogwheel” rigidity - this is rigidity mixed with a tremor
What would Parkinson’s disease look like through imaging?
Structural imaging (CT, MRI) in PD is usually normal or shows non-specific age related change
There is no problem with the structure of the brain, but with the release of dopamine
What type of imaging is used to detect Parkinson’s disease?
DaTscan
this is a nuclear medicine scan where a tracer (radioactive iodine) is injected that binds to dopaminergic neurones
this shows how many receptors are present and whether there is a reduction, suggesting neurodegenerative parkinsonian disease
What would a normal result and a Parkinson’s disease result look like on a DaTscan?
What are the drawbacks of using this test?
- Normal shows a “comma”
- Parkinson’s disease shows a “full-stop”
- ionising radiation is not specific to Parkinson’s disease
- this test cannot distinguish between ‘Parkinson Plus’ conditions
- the DaTscan will be normal if dopamine is blocked due to drugs
What is involved in the non-pharmacological treatment of Parkinson’s disease?
- Physiotherapy
- occupational therapy
- speech and language therapy
What is involved in the pharmacological treatment of Parkinson’s disease?
Drugs to increase dopaminergic stimulation of the remaining neurones in the basal ganglia
this treats the movement symptoms
What are the stages involved in dopamine metabolism?
- Tyrosine is converted to L-Dopa by tyrosine hydroxylase
- L-dopa is converted to dopamine by dopa decarboxylase
- dopamine is broken down into inactive metabolites by monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT)
What are the 4 mechanisms of pharmacological motor treatment?
- Dopamine replacement - levodopa + dopa decarboxylase inhibitor
- dopamine agonists
- monoamine oxidase inhibition (MAO-B)
- Catechol-O-methyl transferase (COMT) inhibitors
What are examples of dopamine replacement drugs?
Levodopa + dopa decarboxylase inhibitor
- co-careldopa
- co-beneldopa
- duodopa
What are examples of monoamine oxidase inhibitors?
- Rasagaline
- selegaline
- safinamide
What are examples of dopamine agonists?
- Ropinerole
- pramipexole
- rotigotine
- apomorphine
What are examples of catechol-O-methyl transferase inhibitors?
- Entacapone (with carbidopa/ levodopa)
- tolcapone
- opicapone
Which drugs work by the following mechanisms?
Levodopa is the precursor of dopamine
dopa decarboxylase prevents it from being broken down in the blood, so that it can become available in the brain
Why may dopamine agonists lead to impulse control disorders?
The reward pathway (mesolimbic) leads to release of dopamine when stimulated
drugs stimulate these pathways, leading to the release of dopamine
this can lead to increased impulsivity and risk-taking behaviours
What are some of the adverse effects of too much dopaminergic stimulation?
- Dyskinesia - abnormal movements
- confusion
- hallucinations
- impulse control disorders
over time, the balance between giving enough drugs to promote “on” state but not too much that dyskinesia (or other adverse effects) occur
What happens to the therapeutic window for pharmacological motor treatment as disease progresses?
At diagnosis there is a very large therapeutic window and patients respond well to dopamine agonists
as the disease progresses, the therapeutic window narrows
the patient is either “on” with dyskinesia or “off” with slow parkinsonian movements
patient can go from being stiff and slow to having excessive movements with no correlation to when medication is taken
What factors need to be considered when “balancing things out” with medication?
Movements:
- tremor
- rigidity
- bradykinesia
mental state:
- confusion
- hallucinations
- delusions
What are the 3 main advanced therapies for PD?
- Apomorphine - a dopamine agonist placed under the skin
- Duodopa - dopamine agonist gel in the duodenum
- deep brain stimulation - inhibits output pathways from the basal ganglia, allowing medication doses to be reduced
What is meant by REM sleep behaviour disorder?
When does it occur?
It is a brainstem problem so can arise a long time before symptoms are noticed
It is not like sleep walking as the patient doesn’t tend to leave the bed
the brain is active and dreams are occurring during REM sleep
