8.2 Parkinson’s Disease Flashcards
Define Parkinsonism
Umbrella term for symptoms of Parkinson’s
What are the 4 cardinal features of parkinsons? (TRAP)
Tremor, Rigidity, Akinesia (bradykinesia), Postural instability
Describe the postural appearance of someone with parkinsonism and explain why
Stooped posture, spine bent forward and legs flexed. This allows the person to stay upright by overcoming the lack of back muscle function due to the bradykinesia. The knee flexion is a result of the stooped posture to compensate for lack of back muscles, NOT a symptom of Parkinson’s itself.
What is meant by a ‘masked face’ in a patient with parkinsons?
Masked face, because muscles don’t get activated often patients appear as if they are wearing a mask… ‘appear emotionless’. Reduced blinking is also seen
Describe the GATE of a patient with parkinsons
Short shuffling gate, ‘Akinesia’ (‘Braykinesia’ because there is some movement)
What is the defining feature of Parkinsons?
Bradykinesia (very specific to lack of dopaine in the basal ganglia)
Give 4 possible causes/associations with parkinsons and highlight the MAIN one
1) Idiopathic: most common (95%)
2) Genetic (rare) both autosomal dominant and recessive types exist
3) Vascular: multiple white matter infarcts
4) Post-infectious: post encephalitic parkinsonism
Name a medication that should NOT be given to a patient with Parkisnons and explain why
antiemetics, antipsychotics (dopamine antagonists)
In a patient with parkinsons, dopamine is already low and thus giving meds that block dopmine will put patient in a ‘parkinsonian crisis’ (extreme ridgidity and Akinesia)
Overall what is the action of dopamine on the direct vs indirect pathway?
Dopamine has an overall excitatory effect on the direct pathway and an inhibitory effect on the indirect pathway
Dopamine is constantly acting on either pathway depending on the responce required/decided by the basal ganglia
Describe the direct pathway
Describe the indirect pathway (The NO-GO pathway)
What releases dopamine in the motor pathway?
Substantia Niagra Compacta
Describe how loss of dopamine in Parkinsons affects the NO-GO system
Loss of dopamine leads to an increase in inhibition of the basal ganglia onto the cortex. Hence, we no longer have the GO signal and thus we NO-GO ➞ bradykinesia
What causes ‘Rigidity’
Tremor in muscles causes increased tone ➞ resistance to passive movement ‘cog-wheel’ ➞ rachet like interruptions
Creates a more flexed posture
Compare the effect on muscles in Parkinsons vs UMN lesions
Parkinsons: Agonist and antagonist muscles affected equally
UMN rigidity: Is greatest at the start and called ‘clasp-knife’
What is Akinesia (bradykinesia)
Slowness of voluntary movement due to a reduction in automatic movement – e.g arm swing when walking
Power retained
Describe the features of a tremour seen in a patient with parkinsons
‘pill-rolling’ rhythmic flexion/extension of fingers, supination-pronation of forearm
Increases during stress and reduces on movement
This is a resting tremour!
Describe the distribution of muscles affected in Parkinsons
Usually asymmetrical
What 2 features of parkinsons causes the ‘cog-wheel’ movement?
Ridgity and Bradykinesia (start-stop-start-stop etc…)
Why must we ask the patient to do BIG and FAST movements to elicit Bradykinesia
because we want to tire out their remaining dopamine. The remaining dopamine in the basal ganglia is able to provide some manner of go, but over time repetitive movements require a repeating go signal and dopamine is not an infinite resource hence, it is used up.
How do we manage Parkinsons disease? (include the patho of the drug you have mentioned)
Nothing slows the progress of PD
Treatment of choice is dopamine replacement with levodopa ➞ L-Dopa + peripheral decarboxylase inhibitors
L Dopa is a precursor of dopamine which is converted both peripherally and centrally by decarboxylation. As the majority of dopamine is converted peripherally before it reaches the brain we need to block peripheral decarboxylase using dopadecarboxylase inhibitors.
Also, only the precursor form of dopamine can cross the BBB and thus using dopadecarboxylase inhibitors prevents conversion into dopamine untill it reaches the brain
List 4 side effects of levodopa (L-dopa)
Nausea, hypotension, hallucinations, nightmares
Prolongued use of levodopa (L-dopa) can lead to what?
Explain why this occurs and when it is most prevelant?
Dyskinesias begin to appear due to receptor hypersensitivity which is worse at beginning of dose
Explain why the ‘on and off phenomenon’ of levodopa (L-dopa) occurs
When it is most prevelant
Worse symptoms occur at end of dose which can lead to ‘’on and off’’ phenomenon
This is because dopamine is stored in the brain and in early stages of disease one dose can last several hours
BUT after about 5 years brain loses ability to store dopamine so ‘’wearing off’’ occurs and doses become effective for shorter times
Give an agonist of dopamine that can be given instead of dopamine
Pramipexole
What 2 enzymes are involved in the breakdown of dopamine?
Give 2 drugs that inhibit each of these enzymes
MAO-B and COMT
MAO inhibitors (Rasagiline)
COMT inhibitors (Entacapone)
Give one other drug that may be used in management of Parkinsons
antimuscarinics
What is Huntington’s disease (incl its inherritance and mutation)
What is the average age of onset?
Progressive movement disorder with dementia
Autosomal dominant mutation of polyCAG on chromosome 4
Normal 20-40 adult onset
What is seen in the cortex of a patient with Huntingtons?
Cerebral atrophy particularly in the cortex, caudate and putamen
Describe the classical sign of Huntingtons
Progressive chorea: ceaseless rapid, jerky movements
(sign onset usually 30-40yrs old with death within 15yrs)
Give 3 management options for Huntingtons disease?
1) Psychological support
2) Antipsychotics
3) Tetrabenazine
** No treatment
What is Wilsons disease? (incl its inherritance)
Give 3 clinical features
Autosomal recessive disorder of copper metabolism.
If untreated causes neurological and hepatic dysfunction because copper accumulates in the basal ganglia, liver and eye
Clinical features: diverse
- Kayser-Fleischer rings
- Liver failure
- Parkinson’s–like tremor, dysarthria
What would be seen in an investigation of Wilsons?
How would you treat?
Investigations: raised urinary copper, reduced caeruloplasmin (carries Cu2+ around) and reduced serum copper
Treatment: penicillamine which chelates copper and increases excretion
Give 3 other important movement disorders
1) Benign essential tremor: tremor seen in fine movement
2) Dystonias: abnormal state of sustained muscle contraction
3) Parkinsonism: various drugs antagonise the dopamine receptors (This is really important!)
Give 5 types of Dystonias
1) Cervical dystonia
2) Writer’s cramp
3) Blepharospasm
4) Tic syndromes
5) Drug induced: antipsychotics, haloperidol, metoclopramide
What is Wernicke encephalopathy and what is the triad of symptoms seen
Cerebellar disorder caused by a Thiamine (vit B1) deficiency
Commonly seen in chronic alcoholics
Triad CF:
- Confusion
- Ophthalmoplegia (eye muscle paralysis)
- Atxia (no muscle control)
What can vertebrobasilar insufficiency (problem with basilar arteries) lead to?
Cerebellar infarct ➞ Ipsilateral limb ataxia, lateropulsion and hypotonia
List 4 common causes of cerebellar disorders
1) Alcohol
2) Hypothyroidism
3) Drug: Phenytoin, Li, amiodarone
4) Genetic
