Parkinson's Disease Flashcards
What is Parkinson’s disease?
- a progressive neurodegenerativve condition
- caused by degeneration of dopaminergic neurones in the substantia nigra
- this is part of the basal ganglia, which has a role in regulation of motor signalling
there is a gradual but progressive fail in the production of dopamine
What is the classic triad of symptoms?
What is significant about these symptoms?
- bradykinesia
- resting tremor
- rigidity
- these symptoms are ASYMMETRICAL with one side being affected more than the other
Who is typically affected by Parkinson’s disease?
- it is twice as common in men
- the mean age of diagnosis is around 65 years
How is the tremor in Parkinson’s disease described?
“pill rolling tremor”
- it looks as though they are rolling a pill between their fingertips and thumb
What is the frequency of the tremor?
4-6 Hz
it occurs 4 to 6 times each second
When is the tremor worse / better?
- the tremor is more pronounced when resting
- it improves during voluntary movement
- it becomes worse when the patient is distracted or stressed / tired
ask the patient to perform a task with the other hand (e.g. mime the motion of painting a fence) will exaggerate the tremor
What is significant about the tremor?
it is unilateral
How is the rigidity in Parkinson’s disease described?
“cogwheel rigidity”
- when passively flexing / extending the arm at the elbow, there is tension in the arm that gives way to movement in small increments (small jerks)
- this is due to the superimposed tremor
this is different to “lead pipe rigidity” in which there is uniform resistance to movement
What is meant by bradykinesia?
- this describes how movements beome smaller and slower
- there are often hesitations / pauses during continued movement
sometimes described as hypokinesia = this is a decrease in amplitude of movement
What symptoms result from the development of bradykinesia?
- handwriting becomes smaller and smaller (micrographia)
- they have a “shuffling gait” as can only take small steps when walking
- difficulty initiating movement (e.g. from standing still to walking)
- difficulty in turning around, having to take many small steps
- hypomimia - reduced facial movements + facial expressions
How is gait changed in Parkinson’s disease?
- they have a “shuffling gait” as they take many small steps
- there is reduced arm swinging
- they also have a stooped posture
What other features can sometimes affect patients with Parkinson’s disease?
- depression
- sleep disturbance / insomnia
- REM sleep behaviour disorder
- anosmia (loss of sense of smell)
- postural instability
- cognitive impairment + memory problems
What are the differences between a Parkinson’s tremor and benign essential tremor?
- BET tends to improve at rest
- it is symmetrical
- it is worse with intentional movement
- it improves with alcohol
What are the 4 main Parkinson’s-plus syndromes?
- multiple system atrophy
- dementia with Lewy Bodies
- progressive supranuclear palsy
- corticobasal degeneration
What is multiple system atrophy?
- the neurones of multiple systems in the brain degenerate
- the degeneration of the basal ganglia results in a Parkinson’s presentation
- the degeneration in other areas leads to autonomic + cerebellar dysfunction
What are the additional symptoms seen in multiple system atrophy?
cerebellar dysfunction:
- ataxia
autonomic dysfunction:
- constipation
- postural hypotension
- abnormal sweating
- sexual dysfunction
What is dementia with Lewy bodies?
- a type of dementia associated with features of Parkinsonism
- it causes progressive cognitive decline
- there is a decline in thinking, reasoning + independent function
What is dementia with Lewy bodies?
- a type of dementia associated with features of Parkinsonism
- it causes progressive cognitive decline
- there is a decline in thinking, reasoning + independent function
What are some of the symptoms associated with Lewy body dementia?
- REM sleep behaviour disorder
- fluctating consciousness
- recurrent visual hallucinations / delusions
- spontaneous changes in attention / alertness
What is REM sleep behaviour disorder?
- a sleep disorder in which the patient physically acts out vivid, unpleasant dreams during REM sleep
- this involves vocal sounds and sudden, often violent arm and leg movements
How can Lewy body dementia be differentiated from isolated Parkinson’s disease?
- cognitive impairment typically occurs before parkinsonism
- both features tend to occur within 1 year of each other
- in PD, the motor symptoms tend to present at least one year before the cognitive symptoms
What is the characteristic pathological feature of Lewy body dementia?
- positive immunohistochemistry staining for alpha-synuclein
- the Lewy bodies within the substantia nigra stain brown
What 2 main features are unique to Lewy body dementia and do not occur in other forms?
- cognition is fluctating - this does not occur in other forms of dementia
- there are early impairments in attention + executive function (in Alzheimer’s there is just memory loss)
What medication must be avoided in Lewy body dementia?
neuroleptics
- patients are very sensitive and may develop irreversible parkinsonism
- the patient will deteriorate rapidly following introduction of an antipsychotic agent
neuroleptics = medications that block dopamine receptors
e.g. haloperidol, olanzapine, clozapine, paliperidone, thioridazine etc.
What is the treatment for Lewy body dementia?
- the same treatment for Alzheimers
- acetylcholinesterase inhibitors and memantine are used
- ACh esterase inhibitors = donepezil + rivastigmine
How are the symptoms of drug-induced parkinsonism different?
- the motor symptoms are rapid onset and bilateral
- rigidity and resting tremor are uncommon
How is Parkinson’s disease diagnosed?
- diagnosis is clinical by a specialist with experience in diagnosing Parkinson’s
- NICE recommend using the UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria
- SPECT can be considered if there is difficulty differentiating from BET
SPECT = single photon emission computed tomography
Who can initiate treatment for Parkinson’s disease?
- management is guided by a specialist
- management is tailored to each individual patient and their response to different medications
What is the most effective drug for controlling motor symptoms in PD?
Who is this offered to?
levodopa
- this is synthetic dopamine
- it is offered to newly diagnosed patients whose motor symptoms are significantly affecting their QoL
- it tends to be reserved for when other treatments are not managing to control symptoms
- this is because it becomes less effective over time
What must levodopa be co-prescribed with?
peripheral decarboxylase inhibitors
- these stop the levodopa from being broken down before it enters the brain
- e.g. carbidopa and benserazide
What combination drugs can be given that include levodopa + peripheral decarboxylase inhibitor?
co-benyldopa:
- levodopa + benserazide
co-careldopa:
- levodopa + carbidopa
What is the main side effect associated with levodopa?
- when the level of dopamine is too high, patients can develop dyskinesias
- these are abnormal movements associated with excessive motor activity
What are the 3 main dyskinesias associated with excessive dopamine?
chorea:
- abnormal involuntary jerking movements
athetosis:
- involuntary writhing movements, usually in the fingers or feet
dystonia:
- excessive muscle contraction results in abnormal postures / exaggerated movements
What medication may be given to extend the effective duration of levodopa?
entacapone
- this is a COMT inhibitor
- the COMT enzyme metabolises levodopa in the body / brain
- inhibiting COMT enzyme slows the breakdown of levodopa to extend its effective duration
COMT = catechol-o-methyltransferase
How do dopamine agonists work?
What are examples?
- they mimic dopamine in the basal ganglia to stimulate dopamine receptors
- examples include:
- bromocryptine
- pergolide
- carbergoline
When are dopamine agonists used in the treatment of PD?
- they are used to delay the use of levodopa
- and then in conjunction with levodopa to reduce the dose of levodopa needed to control symptoms
- they are LESS EFFECTIVE than levodopa in controlling symptoms
What is the most significant side effect of dopamine agonists?
pulmonary fibrosis
How do monoamine oxidase-B inhibitors work?
- monoamine oxidase enzymes break down neurotransmitters such as adrenaline, serotonin & dopamine
- MAO-B is more specific to dopamine
- MAO-B inhibitors block this enzyme to increase circulating dopamine
When are MAO-B inhibitors used to treat PD?
- they are used to delay the use of levodopa
- they are then used in conjunction with levodopa to reduce the dose needed to control symptoms
What are examples of MAO-B inhibitors?
- selegiline
- rasagiline
