Week 2 - F - Parkinsons Disease (symptoms, treatment) and Parkinsonism Flashcards
Where specifically in the substantia nigra does the loss of dopaminergic neurons occur in Parkinson’s disease?
It is the loss of dopaminergic neurons in the substantia nigra pars compacta
There are two common types of increased muscle tone What are they and how are they differentiated? What are the different regions of the brain affected?
Spasticity - occurs with upper motor nueron lesions affecting motor pathways in the motor cortex, cerebral hemispheres, brainstem and spinal cord - pyramidal display and velocity dependent
Rigidity - occurs in extrapyramidal conditions affecting the basal ganglia, commonly Parkinsons - this is extra-pyramidal and non-velocity depndent
Is rigidity or spascticity seen in Parkinsons and therefore what region of the brain is affected?
Rigidity is seen in Parkinsons - meaning the basal ganglia is affected
Movement disorders in the cerebellum show ataxia
What are the features of cerebellar lesions?
Cerebellar lesions - DANISH
Diadochokinesis - inability to make antagonist movements in succession
Ataxia - balance, co-ordination and speech
Nystagmus
Intention tremor - finger-nose testing
Slurred speech
Hypotonia
What are the hyperkinetic movement disorders as seen in extrapyramidal lesions?
Chorea - rapid, irregular voluntary movements typically involving proximal and distal muscles
Tremor - oscillation of agonist & antagonist muscle groups
Tics - sudden fast irregular movement usually in the same muscle group
Myoclonus - sudden fast irregular movement usually in the same body part
Sustained muscular spasms - dystonia
Chorea is the rapid irregular inovluntary muscle movements WHat type of appearance does this give? What are the three hallmark symptoms of parkinson’s?
Gives a dance like appearance in chorea
Parkinson’s - rigidity, bradkinesia, tremor
What are the dance like movements in chorea known as if the amplitude of the movements is large?
This would be Ballismus
What are the five regions of the basal ganglia? Name the groups they are sometimes called
- Caudate nucleus
- Putamen
- Globus Pallidus
- Subthalamic nucleus
- Substantia nigra
Caudate nucleus + Putamen + Globus Pallidus - corpus striatum
Cuadate nucleus + putamen - striatum
Putamen + Globus Pallidus - lentiform nucleus
Which part of the basal ganglia lies lateral to the lateral ventricles? Which is medial, putamen or globus pallidus? Which lies inferior immediately to the thalamus? What lies between the thalmus and the globus pallidus?
Caudate nucleus is lateral to lateral ventricles
Globus pallidus is medial to the putamen
Subthalamic nucleus is inferior to thalamus
INternal capsule is located between the globus pallidus and thalamus
What are the main functions of the cerbellum and the basal ganglia?
Cerebellum - mainly controls movement and coordination
Basal ganglia - Facilitates purposeful movement and inhibits unwanted movement - also has a role in posture and muscle tone
When the cortex tries to form a movement, the information are relayed via the basal ganglia and cerebellum before retunring to the cortex and then the motor tracts
When information reaches the basal ganglia, what region of the basal ganglia recieevs the info?
This would be the caudate nucleus
What are the four cardinal symptoms of Parkinsons disease?
Bradykinesia
Rigidity
Rest tremor
Postural and gait impairment
Motor features in PD are heterogenous, but there are broadly 2 subtypes What are the two subtypes of Parkinsons?
Tremor dominant where other motor symptoms such as bradykinesia and postural and gait disturbances arent as bad and Non-tremor dominant where all other motor symptoms are seemingly worse
Non-‐motor symptoms are common in earlyPD (as well as before the onset of motor features) and associated with reduced health-‐related quality of life What are some non-motor symptoms associated with Parkinson’s disease?
Sleep disorders (insomnia)
Memory problems
Olfactory dysfunction - anosmia
Autonomic dysfunction may also present eg urinary incontinence and constipation
Diagnosis occurs with the onset of motor symptoms Non-‐motor symptoms can be present for more than a decade before motor onset What is Parkinson’s disease due to?
It is due to the degeneration of the dopaminergic neurons in the substantia nigra pars compacta
What type of dementia occurs with Parkinson’s disease? Seen in over 80% of patients after having Parkinson’s for at least 20 years
This would be Lewy-body dementia
Advanced stages of Parkinsons are characterized by the emergence of complications related to long-‐term symptomatic treatment What are some of the advanced stage treatment complication symptoms? What are treatment resitant symptoms also?
Treatment complications - dyskinesis and psychosis
Treatment resistant - freezing gait, postural imbalance, speech dysfucntion
What are the options for treating the parkinsons treatment induced pshycosis?
Psychotic symptoms (hallucinations and delusions) with all Parkinson’s disease treatments (and the higher risk with dopamine agonists).
If the psychosis is well tolerated do not treat
Can try offering an atypical antipsychotic such as quetiapine - works more on serotonin channels than dopamine like the typicals If this fails then clozapine - rigorous monitoring
Under a microscope what can be seen in the substantia nigra neurons before they die? On gross examiantion what does the substantia nigra look like in parkinsson? What region of the brain does the substantia nigra lie?
- -Can see a-synuclein protein forming Lewy bodies or Lewy nitrites under a microscope
- -On gross examination the darker substantia nigra appears to have faded due to the dopaminergic neurons dying (can see the cerebral aqueduct hole also)
- -Superior midbrain
Why are the non-motor symtpoms of Parkinson’s thought to occur? Eg autonomic dysfunction (urinary incontinence and constipation), sleep disruption, anosmia
Thought to come about due to dysfunction in other parts of the brain ie the prefrontal cortex
Rapid eye movement sleep behaviour disorder is one of the sleep disturbances that may occur in Parkinson’s disease What occurs in this condition? How is this disorder diagnosed?
REMSBD is a type of parasomnia
Parasomnias are a category of sleep disorders that involve abnormal movements, behaviors, emotions, perceptions, and dreams that occur while falling asleep, sleeping, between sleep stages, or during arousal from sleep.
Diagnosed using an overnight polysomnography
Polysomnography, also called a sleep study, is a test used to diagnose sleep disorders.
What is the treatment for rapid eye movement sleep behaviour disorder?
1st line - clonazepam - benzodiazepine or melatonin at bedtime is the treatment for this
UK Parkinson’s disease Scociety Brain Bank clinical diagnostic criteria This includes bradykinesia + one or more of which symptoms?
Muscular rigidity 4-6Hz tremor
Postural instability
Pathological hallmarks are loss of dopaminergic neurons within the SNpc (substantia nigra pars compacta) and Lewy body pathology What would be seen on microscopy of the substantia nigra again?
Would see the misfolded a-synuclein protein which forms Lewy bodies and Lewy nitrites
a-synculein (SNCA - synuclein-alpha) protein is what forms the lewy body in Parkinson’s disease What is the most common and second most common neurodegenerative diseases?
Alzheimer’s disease is the most common neurodegenerative disease Parkinson’s disease is the second most common neurodegenerative disease
What gender is most commonly affected by Parkinson’s disease? Increasing age is a big factor in Parkinson’s, Above what age is age a risk factor?
Male are more commonly affected 3:2- and above the age of 40 is when risk of Parkinson’s increases
Which two genes are most commonly associated with autosomal dominant and autosomal recessive parkinsons if they have acquired a mutation?
Autosomal dominant - this would be the LRRK 2 gene Autosomal recessive - this would be the Parkin gene
The genetic contribution to Parkinson’s has long been recognized by the increased risk associated with a positive family history of parkinson’s or tremor What was the first gene to be associated with Parkinson’s? What is the most important gene associated with Parkinsons?
SNCA which encodes alpha-synuclein was the first gene to be associated with Parkinson’s
Mutation in the GBA gene is the greatest genetic risk factor for Parkinsons disease
currently parkinson’s disease only has symptomatic treatment control but we are unable to stop the neurodegeneration What is the mainstay drug for Parkinson’s treatment? how does this drug work? What is it often given in combination with and why?
Mainstay drug is levodopa Works by crossing blood brain barrier where it is converted to dopamine (dopamine cannot readily cross blood brain barrier itself) - try not to start early
Often prescribed as a levodopa/carbidopa combination drug Carbidopa inhibits the aromatic amino acid decarboxylase which breaks down levodopa peripherally therefore reducing its levels in the brain
Which 2 type of drug can be given as monotherapy in mild Parkinsons? Give an example of these drugs and how they work
Dopamine agonsits - monotherapy if PArkinson’s isnt too severe
Ropinirole and bromocriptine - they act on the D2 agonists in the brain
They can be given in mild PD and hence lower the starting dose of levodopa when it is required MOA-B inhibitors - monamine oxidase B inhibitors- eg selegilline as an alternativ to dopamine agonsits in early PD - MAO-B breaks down dopamine usually
What is the other enzyme apart form aromatic amino acid decarboxylase that breaks down levodopa known as and there is therefore a drug for this?
This enzyme is catechol-o-methyltransferase and COMT inhibitors exist to prevent this enzymes effects
Examples are entacpne and tolcapone
Impulsive control disorders often occur when people take dopamine agonists When should dopamine agonists be avoided?
In people with a history of addiction, OCD, and in the elderly or cognitively impaired as it increases the risk of hallucinations
Why is it wise to delay the starting dose of levodopa or only use when really needed?
- After 5-10 years, wearing off, dose of Levodopa starts being less effective and patient needs more drug to stop their symptoms coming back.
- Therefore, delay starting Levodopa early on in disease or use Levodopa along with Dopamine Agonist Dopamine agonsits / MOAB inhibitors, first line then COMT inhibittors, levodopa
Levodopa provides the greatest symptomatic benefit, but long term use is associated with motor complications (dyskinesia and motor fluctuations) What drug can be given for these symptoms?
Amantadine - weak dopamine agonist
New patient with Parkinson’s disease presents Which drug can be prescribed? WHich drug is also an option for 1st line treatment? If PArkinson’s progresses, what is the treatment option?
Prescribe a dopamine agonist - ropinirole or bromocriptine
Can try a Monoamine oxidase B inhibitor (MAO-B inhibitor) eg selegeline or rasagaline
Precribe levodopa if parkinsons progresses with a dopa-decarboxylase inhibitor - eg carbidopa or methyldopa
Psychosis in PD is most efficiently managed with which drug? What is depression in PD managed with? If somebody presents with delirium and has PD, which drug choice is given?
Well managed with clozapine - or quetiapine (both anti-psychotics)
Depression is managed with SSRI - eg citalopram or fluoxetine or even tri-cyclic antidepressants
Delirium if the person has PD or Lewy body demtentia- give quetiapine and not haloperidol (has slight dopamine antagonsit actions)
What is Parkinsons associated dementia treated with (Lewy body)? What other type of dementia is this drug used in?
Rivastigmine - anticholinesterase inhibitor
Used in Lewy body dementia and Alzheimer’s dementia
What are the four cardinal signs of Parkinson’s disease? How many Hertz is the tremor and what is it described as? What type of gait?
Rest tremor - 4-6Hz and pill rolling tremor
Muscular rigidity
Bradykinesia
Postural and gait impairment - stooped posutre and shuffling gait
How is the tremor best elicited in Parkinsons? What is the decreased facial expression and eye blinking known as? Is parkinson’s disease asymmetrical or symmetrcial? ie are the motor symptoms asymmetrical or not
Best elicited whilst patient is focussed on a mental task ie counting back from 100
This is known as hypomimia
The motor symptoms in parkinsons disease are asymmetrical
Vascular Parkinsonism Which part of the body does this particularly affect? Which motor parkinoson disease sign is absent here?
This predominantly affects the lower limbs (lower limb Parkinson’s)
Rest tremor is usually absent however
There is a poor levodopa response seen here
Parkinsonism can happen due to drugs What drug group is the most common cause of Parkinsonism? Name a drug given for gastroparesis that also causes it?
Neurleptic drugs ie antipsychotic drugs - parkinsons induced psychosis needs treated but can worsen parkinson symptoms
Metoclopramide
Name 2 neurleptics(anti-psychotics) that can be given in Parkinson’s? Would group of anti-psychotics do they belong to? name the one not to be given to treat delirium?
Dont give haloperidol
Clozapine and quetiapine belong to the atypical anti-psychotics - less effect on dopamine
