Parkinson's Disease Flashcards
PD is an example of what type of movement disorder? Is this pyramidal or extrapyramidal?
Hypokinetic / extrapyramidal
Which part of the brain is affected in PD?
Basal ganglia
What specific part of the basal ganglia is affected in PD?
The pars compacta region of the substantia nigra
What is the key pathological feature of PD?
Loss of dopaminergic neurones in the substantia nigra
Sections through the brainstem in a PD sufferer would show what? What does this correlate with?
Loss of the normally dark black pigment of the substantia nigra / correlates with dopaminergic cell loss
Symptoms of PD generally do not tend to show until there is what?
Loss of around 60% of neurones in the substantia nigra
The neurones which remain in the substantia nigra in PD can often accumulate what? Within where?
The protein alpha-synuclein within Lewy bodies
What are Lewy bodies?
Abnormal aggregates of protein that develop inside nerve cells
In terms of describing the pathophysiology of PD, the degeneration of dopaminergic neurones in the substantia nigra are associated with what? Which leads to what?
A decrease in dopamine levels which leads to increased basal ganglia inhibitory output and hypokinetic symptoms
What are the risk factors for developing PD?
Increasing age, male gender, family history, other environmental/genetic factors
What feature increases the probability of a genetic cause for PD?
Early onset, particularly < 40 years
A mutation in the PARK2 gene is responsible for causing what?
Typical, early onset (< 50 years) PD
A mutation in the ATP13A2 gene is responsible for causing what?
Atypical, juvenile onset (children/teens) PD
Around 50% of patients with PD aged < 50 have a mutation in which gene?
PARK2
LRRK2 and SNCA are both genes in which mutations can lead to PD. How are these inherited?
Autosomal dominant
PARKIN and PINK1 are both genes in which mutations can lead to PD. How are these inherited?
Autosomal recessive
What are the 3 main groups of symptoms of PD?
Hypokinetic motor symptoms, hyperkinetic motor symptoms and non-motor symptoms
What are the 3 main hypokinetic motor symptoms of PD?
Bradykinesia/akinesia, rigidity and postural instability
The rigidity in PD is often described as what?
Cogwheeling
Rigidity is a feature of PD which can cause what?
A stooped posture and an expressionless ‘mask like’ face
Which of the 3 main hypokinetic motor features of PD usually develops last? This can often lead to what?
Postural instability, often leads to falls
What is the only hyperkinetic motor feature of PD?
Resting tremor
What are the 4 main non-motor features which can be seen in PD?
Hyposmia/anosmia, sleep disorders, depression/psychosis/dementia, autonomic features
What are some examples of autonomic features which may be seen in PD?
GI/bladder dysfunction, postural hypotension
Motor features in PD are heterogenous, but what are the two broad subtypes?
Tremor dominant (with relative absence of other features) and non-tremor dominant
What are the outcomes of tremor dominant PD when compared with non-tremor dominant PD?
Slower rate of progression and less functional disability
How do the motor symptoms of PD usually start?
They usually start asymmetrically, often as a resting tremor in one arm
In PD, what tends to come first - motor or non-motor symptoms?
Non-motor
Essential Parkinsonism can be defined as bradykinesia and at least one of what other features?
Resting tremor, postural instability or rigidity
What are some additional motor features of PD which are not included in the criteria for essential Parkinsonism?
Stooped, fixed or dystonic posture, hypomimia (masked face), shuffling gait
What is cogwheel rigidity?
A superimposed clicking resistance, often attributed to the underlying tremor
What is lead pipe rigidity?
Constant resistance throughout passive movement
Idiopathic PD is diagnosed how?
It is a diagnosis of exclusion
Idiopathic PD is a clinical diagnosis and can be confirmed with what?
Essential Parkinsonism, no alternative explanation for symptoms (e.g. drugs), responsiveness to Levodopa
Before diagnosing idiopathic PD, what should you exclude?
Treatable causes of asthenia e.g. anaemia or hypothyroidism
Does tremor occur in all patients with PD?
No, around 70%
Patients with idiopathic PD should NOT present with what?
Early onset bulbar problems, dementia/hallucinations, eye movement disorder or intrusive autonomic features
What is a useful test to do to diagnose PD and why?
Idiopathic PD usually responds to treatment with Levodopa, so a trial of this to see if there is an improvement in symptoms is a good test to do
What test can be done to visualise neurodegeneration in the basal ganglia in PD?
MRI
What test can be done to assess dopamine levels in the basal ganglia in PD?
SPECT
In PD, symptomatic treatments are used to do what?
Enhance intracerebral dopamine or stimulate dopamine receptors
What is the main symptomatic drug for PD and what is its mechanism of action?
Levodopa - a dopamine precursor
What is the 2nd line symptomatic drug group for PD? What are some examples?
Dopamine agonists - apomorphine, ropinirole and pramipexole
What are some last line symptomatic drug treatments for PD?
Monoamine oxidase type B inhibitors and amantadine
Why is dopamine itself not used to treat PD?
Because it does not cross the BBB
When should treatment for PD be initiated?
When symptoms are causing discomfort and disability
Which symptoms of PD respond reliably to dopaminergic treatment in early disease?
Bradykinesia and rigidity
Which symptom of PD is inconsistently responsive to dopaminergic treatment?
Resting tremor
What can be an effective treatment for tremor in PD?
Anticholinergic agents e.g. trihexyphenidyl
What are some non-oral therapies that can be used for PD?
Continuous apomorphine infusions and deep brain stimulation
Dopamine agonists and Levodopa are associated with what side effects?
Nausea, daytime somnolence and oedema
Dopamine agonists can cause what kind of disorders?
Impulse control disorders
Dopamine agonists should not be prescribed in who?
Patients with a history of addiction/OCD/impulsive personalities and the elderly (especially with cognitive impairment)
Which drug used to treat PD has the greatest symptomatic benefit? What are its downsides?
Levodopa / associated with motor complications (dyskinesias) and reduced effect after 5-10 years
Younger patients with PD are often started on which drug first?
Dopamine agonists
What are the main long term complications of dopaminergic therapies for PD?
Motor and non-motor fluctuations, dyskinesias, psychosis
What are motor/non-motor fluctuations?
Alterations between periods of good motor/non-motor symptom control and periods of reduced motor/non-motor symptom control
Which dyskinesias are most likely to be caused by Levodopa? They tend to occur when?
Involuntary chorieform or dystonic movements / when levodopa concentrations are at maximum
What is it known as if involuntary dyskinesias occur at the beginning or the end of a levodopa dose?
Diphasic dyskinesia
What type of hallucinations are most likely to occur in PD?
Visual
What problems with regards to sleep can be seen in PD?
REM sleep disorders and restless legs
