Parkinsonism Flashcards
What is the main cause of Parkinsonism?
Idiopathic Parkinson’s Disease
Describe the pathology of IPD
Loss of dopaminergic neurones in the basal ganglia - most notably the substantia nigra (inadequate dopamine transmission). Surviving neurons contain aggregations of a protein called Lewy bodies.
In some cases Lewy bodies seen throughout brain - in such cases there is often co-existing dementia.
IPD is a slowly progressive disorder, without remission. True or false?
True
What is the mean age of onset of IPD?
45-60
Symptoms of Parkinson’s are seen once levels of dopamine are what percentage below normal levels?
20-40%
Parkinsonism is often described as a triad of…
Tremor
Rigidity
Bradykinesia
Signs are initially worse on one side. True or false?
True - neurodegenerative disorders are not symmetrical
May progress to be bilateral
Describe the tremor seen in IPD
Resting tremor - disappears with deliberate activity
Pill rolling - rolling of thumb over fingers
4-6 Hz
Describe the bradykinesia seen in IPD
Slow movements
Slow to initiate
Decrease in amplitude with repetition
Fine motor movements particularly affected
Describe the rigidity seen in IPD
Increased resistance to passive movement - sometimes called lead pipe rigidity
Rigidity equal in extensors and flexors
Can be called cogwheel rigidity - temporarily gives way at certain points
What signs are associated with the patient’s gait?
Slow Shuffling steps Pitched forward Reduced arm swing Narrow based Turning on block Freezing at obstacles
What non motor symptoms are seen in IPD?
Autonomic dysfunction - postural hypotension, constipation, urinary frequency/ urgency, dribbling of saliva
Sleep disturbance - REM sleep disorder
Depression
Dementia
Hallucinations are common- combination of the disease and drugs used to treat it (often not unpleasant)
Speech - slow and monotonous (may be lost in late stages)
What is typically seen in a patient’s hand writing?
Typically smaller and more spidery
Do patients experience changes in sense of smell?
Yes - anosmia
How is IPD diagnosed?
Clinically - signs and symptoms
To diagnose Parkinsonism what 2 elements are necessary?
Bradykinesia
Rigidity
(Tremor may be predominant in some people, but absent in others)
What does a significant improvement with treatment suggest?
The cause is IPD rather than other causes of parkinsonism
What is the main treatment used?
Levodopa - a dopamine precursor.
Dopamine cannot cross the BBB, so a precursor is given
What is L-dopa given with?
A dopa-decarboxylase inhibitor e.g carbidopa
- prevents too much conversion to dopamine in the peripheries and allows increased amounts of levodopa to cross BBB
How long does it take for the benefits of L-dopa to be seen?
2-3 weeks
What are the side effects of levodopa?
Dyskinesia Painful dystonia - increased tone Psychosis Compulsive behaviours - gambling, sexual Nausea and GI upset On- off effect at end of the dose
Why should levodopa be started late?
Efficacy reduces with time, requiring larger and more frequent dosing, which increases side effects.
Also response fluctuations occur with prolonged use - unpredictable freezing and pronounced end of dose reduced response
Why should levodopa not be stopped suddenly?
Risk of acute akinesia and neuroleptic malignant syndrome
Why are dopamine agonists useful?
They can delay starting levodopa and allow lower doses of levodopa once PD progresses.
What are some examples of dopamine agonists?
Ropinirole
Pramipexole
What are some side effects of dopamine agonists?
Drowsiness, day time sleeping
Hallucinations
Compulsive behaviour
What is Apomorphine?
A potent DA agonist used with continuous SC infusion - evens out end of dose effects.
Or can use rescue pen for sudden freezing
How do COMT inhibitors work?
Prevent methylation of levodopa - so increase its availability
Help with motor complications especially in late disease
What should be closely monitored with COMT inhibitors?
LFTs as can cause hepatic complications
Give an example of a COMT inhibitor
Tolcapone
How do MAO-B inhibitors work?
Reduce the degradation of dopamine secreted by dopaminergic neurons
When are MAO-B inhibitors used?
Any disease stage, but often used as an alternative to dopamine agonists in early PD.
What are the side effects of MAO-B inhibitors?
AF
postural hypotension
What are some examples of MAO-B inhibitors?
Rasagiline
Selegiline
Is IPD more common in men or women?
Twice as common in men
How does the face often appear in IPD?
Mask like
What type of nerve cells are lost in the substantia nigra in IPD?
Pigmented nerve cells
What medication can be given to manage drooling of saliva?
Glycopyrronium bromide
What is dyskinesia?
Involuntary writhing movements
In IPD the patient may initially have an intention tremor. True or false?
True (then may develop to resting)
Why is Haloperidol contraindicated in patients with Parkinson’s disease?
It is a dopamine antagonist that can worsen symptoms
What kind of sleep problems are seen in IPD?
Excessive daytime sleepiness (due to getting poor night sleep or use of dopaminergic medications especially dopamine agonists)
Sleep apnea
REM sleep behaviour disorder (do not have the normal relaxation of muscles during their dreams, so they act them out during REM sleep - may shout, kick, grind teeth)
If excessive daytime sleepiness occurs, what should the patient not do?
Drive
Medication should be adjusted to control symptoms
Modafinil can be considered
How long does it approximately take for levodopa to have reduced effectiveness?
Usually by 2 years
If postural hypotension occurs, what should be done?
Medication review
If symptoms persist - midodrine : acts as on peripheral alpha adrenergic receptors to increase arterial resistance
If a patient with Parkinson’s disease cannot take levodopa orally, what can they be given?
A dopamine agonist patch as rescue medication to prevent acute dystonia.
It is important not to acutely stop levodopa
Why are ergot derived medications not recommended?
Risk of fibrotic reactions
When is amantadine often used?
May reduce involuntary movements (dyskinesia) causes by other Parkinson’s drugs, without making symptoms worse.
Can help reduce stiffness
Antimuscarinics are used to treat mainly…
Drug induced Parkinsonism rather than IPD
Help tremor and rigidity
Examples: procyclidine, benzotropine
What enzyme converts l-dopa to dopamine in the peripheries?
Dopa decarboxylase (Inhibited by carbidopa)
What is the name of the pathway that connects the pars compacta and striatum?
Nigrostriatal pathway
Helps to stimulate the cerebral cortex and trigger movements
Does IPD cause weakness?
No
Helps distinguishing it from motor cortex or corticospinal pathway diseases
As IPD evolves, what are the 4 distinct stages?
Early stage soon after diagnosis - symptoms mild and normal life possible
Maintenance stage - good response to treatment and no major disability
Advanced stage - poor response to drugs with motor side effects
Palliative stage - unable to live independently and in need of multidisciplinary support
IPD is the main cause of Parkinsonism, but there are others….
Drug induced Parkinsonism
Vascular pseudoparkinsonism
Parkinson’s plus syndromes
Describe vascular pseudoparkinsonism
Also called lower limb Parkinsonism
Difficultly walking and maintaining balance
Example: diabetic / hypertensive patient with postural instability and falls
What drugs can cause drug induced Parkinsonism?
Usually those that affect dopamine levels in the brain - antipsychotics, some CCBs, metaclopramide, prochlorperazine
How is drug induced Parkinsonism different from IPD?
Difficult to distinguish
Tremors and postural instability may be less severe
Describe progressive supranuclear palsy
Early postural instability Slowing of movement Difficulty moving eyes - vertical gaze palsy Rigidity of trunk > limbs Symmetrical onset Speech and swallowing problems Little tremor Poorly responsive to levodopa
Describe multiple system atrophy (shy- Drager syndrome)
Early autonomic features - erectile dysfunction, postural hypotension, atonic bladder
Cerebellar signs - impaired balance, so prone to falls
Pyramidal signs
Rigidity more than tremor
When diagnosing IPD, what conditions should be excluded?
Frontotemporal dementia
Cerebellar pathology
If an alternative cause is suspected, what can be done to rule out structural pathology?
MRI
What is a DaTscan?
A tool used to confirm IPD diagnosis
DaTscan is a drug injected into bloodstream - it attaches to the dopamine transporter found on dopamine neurons . Imaging equipment used to identify presence of DaTscan. Less area lights up with PD
Falls early in the disease suggest…
One of the Parkinson’s Plus syndromes
In IPD falls normally occur later in disease
