parkinsons Flashcards
define parkinsons
chronic, progressive neurodegenerative conditions that occurs secondary to loss of dopaminergic neurones within substania nigra
what is parkinsonism?
- Parkinsonism: bradykinesia and at least one of: resting tremor, rigidity, postural instability
who is more at risk of parkinson’s?
Epidemiology: 1.5x more common in men
- One of the most common neurological disorders lifetime risk of 2.7%
- Peaks between ages of 55-65yrs and has slowly progressive onset
what does the basal ganglia do?
Physiology: basal ganglia are involved in movement helps start and fine tune movement by motor cortex
- Functions of basal ganglia: inhibition of muscle tone, coordinated/ slow/ sustained movement, suppression of useless patterns of movement, initiation of movement
what causes parkinson’s?
Aetiology: idiopathic
- Very small proportion (2-3% of the cases) are causes by monogenic causes – single gene variant causing disease
- Majority of cases are linked to complex interaction between genetics and environment
when may parkinson’s present?
PD may not be apparent until a substantial number of neurones have been lost within substania nigra (around 50-80%)
what is the direct pathway within basal ganglia and what does it do?
Direct pathway: mostly stimulatory pathway: shorter pathway and mostly off and linked to D1 receptors
- Activation of direct leads to a series of neural connections through basal ganglia and eventually leads to initiation of movement
- dopamine that is released from substania nigra via dopaminergic neurones are able to activate the direct pathway via D1 leading to generation of movement
what is the indirect pathway in the basal ganglia and what does it do?
indirect pathway: mostly an inhib pathway – a longer and linked to D2 receptors
- activation is essential to inhib muscular tone to prevent unnecessary movement
- dopamine released from substania nigra via dopaminergic neurones are able to inhib the inhibitory pathway generation of movement
how is dopamine involved within parkinson’s?
dopamine: acts on direct and indirect pathway to permit movement generation
- this process is finely tuned and provides coordinated movement
- PD: issue with initiation of movement
how may the symptoms present in PD?
Symptoms: unilateral symptoms at onset with gradual onset that develop into bilateral signs
- Motor symptoms
- Non motor complications: depression, dementia, sleep disturbances, autonomic dysfunction causing ill-health
what are the three main features of PD?
Classic features: bradykinesia, resting ‘pill rolling’ tremor and cogwheel rigidity
what shows bradykinesia?
- Bradykinesia: general slowing of voluntary movements, reduced arm swing, reduction in the amplitude with repetitive movements
what indicates a tremor?
- Tremor: can be induced by distraction, pill rolling movement:
describe pill rolling tremor
rubbing grains of sand in between finger and thumb
how may rigidity present?
- Rigidity: increase resistance to passive movement, cogwheel due to superimposed tremor
apart from the classic three symptoms seen within PD, what other symptoms/ features may be seen?
- Expressionless face – parkinsonian mask
- Micrographia – small writing
- Soft voice
- Drooling of salvia
- Shuffling gait – festinating gait
- Glabellar tap:
- Depression
- Bowel and bowel symptoms: urgency, incontinence, constipation
- Sleep disorder
- Sexual dysfunction
what is glabellar tap?
repeated tapping of forehead and associated with persistent blinking
how is the diagnosis of PD made?
Diagnosis: clinical judgement made by bradykinesia and another major feature of parkinsonism
- UK parkinson’s disease society (PDS) brina bank diagnosis criteria
what are the 4 steps involved in the parkinson diagnosis?
- identification of features
- identify exclusion criteria
- identification supporting PD
- absence of red flags
what signs identify parkinsons?
- Bradykinesia + (muscular rigidty/ postural instability/ resting tremor) - one of the three as well as bradykinesia
what need to be excluded within PD diagnosis?
- Repeated strokes and stepwise progression
- Head trauma – history
- Definite encephalitis
- Sustained remission
- Unilateral features after 3 years
oculogyric crisis
antipyschotic/ dopamine depleting drugs
other atypical neuro features
what is oculogyric crisis?
form of dystonic movement characterised by paroxysmal, conjugate and typically upward deviation of eyeball which can occur for hours to seconds usually acute
what supports parkinsons - need 3 of these points?
- Progressive disorder, unilateral disorder, resting tremor
- Persistent asymmetry
- Excellent response to levodopa
what neuro red flags need to be out ruled for PD diagnosis?
- Rapid development of gait impairment, early bulbar dysfunction, non -progressive motor symptoms, reps dysfunction, early severe autonomic dysfunction
what is parkinson plus syndrome?
group of conditions that may get mistaken for parkinsons
- They affect wider area and can cause more complex disease
what are parkinson plus syndrome examples?
MSA
dementia with Lewy Body
progressive supranuclear palsy
corticobasal degeneration
what is MSA and how is it different to parkinsons?
- MSA: mutli system atrophy – adult onset, rapidly progressive characterised by autonomic dysfunction – severe postural hypotension, urogenital dysfunction poor response to levodopa
what is PSP and how is it different to PD?
- Progressive supranuclear palsy (PSP): typically presents at 50-60yrs and characterised by vertical gae, dysarthria and cognitive decline. Tremor is rare
what is dementia with lewy body and how does it differentiate to PD?
- Dementia with Lewy Body (DLB): early onset dementia with <1yr has Parkinson features. May have hallucinations and fluctuating consciousness
what is seen within corticobasal degeneration?
- Corticobasal degen (CBD): progressive dementia, parkinsonism and limb apraxia.
what is apaxia?
Apraxia: problems with motor planning eg unable to wave hello
what investigations are needed?
- Clinical diagnosis
- Neuro imaging – CT/MRI to rule out others eg cerebrovascular disease
- PET: with fluorodopa to help localise dopamine deficiency within basal ganglia
- Striatal dopamine transporter using 123I-FP-CIT single photon emission CT – DaTscan differentiate Parkinsonism from essential tremor
what are motor complications of PD?
- Motor ‘on-off’ fluctuations- switch from dyskinesia to immobility within minutes
- Dyskinesia – hyperkinetic movement due to dosing of medications
- Freezing of gait – can not complete movement
- Wearing off phenomenon – towards end of dose
- Falls
what are non motor complications of PD?
- Aspiration pneumonia
- Nutritional deficiency, dysphagia, weight loss
- Bladder, bowel and sexual dysfunction
- Pressure sores, postural hypotension
- Impulse control disorders and psychosis
describe the tremor in Parkinson’s?
- Tremor: 4-6Hz, worse at morning (at rest), asymmetrical can be both sides but it will be worse on dominant side, pill rolling
describe features of bradykinesia?
- Micrographia, spidery writing
- Repetitive movements go from large – small
- Face: parkinson’s mask, lack of eye blinking (serpentine stare)
- Gait: slow hesitant, stooped posture, inability to stop or turn, poor arm swing
- Speech: initially monotonous, as PD worsens it becomes tremulous, slurring dysarthria (due to bradykinesia, tremor, rigidity)
describe cogwheel rigidity
- Cogwheel rigidity: seen in those with damage in extrapyramidal damage tracts no matter what pressure/ velocity it will not give way
name some conditions that can have parkinsonism?
dementia with lewy body, wilsons – build up of copper (can go into basal ganglia)
drug induced
parkinson plus syndromes
what drugs can cause parkinsonism?
- Drug induced: dopamine antagonists (anti-psychotics, metoclopramide, MPTP)
describe the parkinson plus syndromes
- Parkinson plus: MSA (Parkinson features + autonomic dysfunction + ataxia), PSP (slow movements + Parkinson + cant look up with eyes)
what features would you assess for parkinson’s?
- Observe: face, tremor (ask them to close eyes and count back)
- Assess upper tone: demonstrate cogwheel rigidity, kinnier Wilson distract them and lift one arm and then test tone on another
- Repetitive hand movements: writhing, glabellar tap (tap forehead eventually you would stop blinking but in PD keep blinking)
- Speech, get them to stand up, assess gait and turning
- Retropulsion and anteropulsion: pulling on shoulders and they would fall in that direction
what is wilsons disease?
disorder of cu metabolism
what is low cauroplasm?
gh urinary copper and low serum copper
what can copper deposition do?
- Copper deposition: basal ganglia disease, liver cirrhosis, kaiser-fleischer rings, kidney disease, low IQ, cardiomyopathy
how would copper deposition cardiomyopathy present on an ECG?
ST segment depression
T wave inversion
how do you treat wilsons disease?
penicillamine (copper chelating agent)
name some tremor differentials?
- Anxiety
- Hyperthyroidism
- Drugs eg B2 agonists
- Cerebellar disease (intentional) stroke, alcoholism, B12 deficient. Seen on finger to nose test
- Essential tremor
describe an essential tremor?
- 5-8Hz
- Tremor occurs when trying to adopt a posture
- Shaking occasionally at rest on intention
- Typically worse on upper limbs
what can make an essential tremor worse?
caffeine, poor sleep, stress/ anxiety
what can make an essential tremor improved?
alcohol
how can manage essential tremor?
: sleep and stress controls. Beta adrenergic antagonists propranolol, primidone, topiramate.
what is chorea?
dance like (choreography) rhythmical, non purposeful movements
what conditions can cause chorea?
- Basal ganglia lesion, huntingtons, sydenham’s (rheumatic fever caused by strep A), benign hereditary chorea
what drugs can cause chorea?
- Drug causes: levodopa, phenytoin, alcohol, oral contraceptive
what is athetosis?
slow moving, typically in fingers
what can cause athetosis?
- Causes: damage to basal ganglia (ischaemia, athetoid cerebral palsy – due to kernicterus, excess bilirubin, associated with dystonia’s)
what is hemiballismus?
: violent, contouring, continuous movements – usually rotational
- Unilateral
what can cause hemiballismus?
- Secondary to infarction/ haemorrhage of contralateral subthalamic nucleus
- Eg left sided stroke would cause this on right side
what is myoclonus?
violent, sudden jerks of single or groups of muscles
what can cause myoclonus?
- Causes: nocturnal, paramyoclonus multiplex
what is seen in neuroleptic complications?
akathisia
acute dystonia
chronic traditive dyskinesia
what is akathisia?
restless, repetitive and irresistible to move
what is acute dystonia?
acute muscle contractions, spasmodic torticollis (neck), trismus (in mouth), oculogyric crisis (dystonia of the eyes)
how is neuroleptic complications get resolved?
IV anti-muscarinics
what is chronic tarditive dyskinesia?
mouthing and lip smacking, grimaces, eye blinking seen after several months of anti-psychotics
what drugs can cause neuroleptic complications?
anti-psychotics and some anti-emetics
what are tics?
idiosyncratic movements of face, neck or hands which are part of normal motor gestures
what can be seen as simple tics?
- Simple tics: sniffing, facial grimaces are common in childhood and may resolve
what is gilles de la tourettes syndrome?
multiple tics (motor and speech)
- Associated with behavioural problems eg ADHD or OCD
- Childhood and adolescence, more common in males
- Lifelong
what is dystonia?
prolonged muscular contraction eg spasm
what are causes of dystonia?
- Causes: primary torsion dystonia, dopamine responsive dystonia,
what drugs can induce dystonia?
- Drug induced: metoclopramide, prochlorperazine, anti-psychotics
how can you distinguish between asterixis and tremor?
Asterixis: can be distinguished from tremor on the basis of prolonged absence of EMG activity during flapping seen in hypercapnia, encephalitis
what signs are seen in Multi system atrophy - MSA?
autonomic dysfunction
cerebellar dysfunction
what is seen with dementia LB?
parkinsons
hallucinations, delusions
REM sleep disorder
fluctuating consciousness
what can be seen in PSP?
balance issues, mobility, frequent falls
change in behaviour
what is PSP?
progressive supranuclear palsy
what is CBD?
corticbasal degeneration
what signs are seen in CBD?
problems recalling words, aphasia, short term memory loss
why is levodopa prescribed with peripheral decarboxylase inhib?
helps dopamine go in
what is COMT inhib?
carbidopa-levodopa
give an example of COMT inhib?
entacapone
what is the MOA of COMT inhib?
prevents dopamine breakdown
give an example of a dopamine agonist?
rotigotine
what is the risk in using dopamine agonists?
pulmonary fibrosis
impulse issues
what can be seen within impulse issues with dopamine agonists?
addiction - internet, sex, shopping
give examples of monoamine oxidase-B inhib?
selegiline
rasagiline
what is the moa of monoamine oxidase B inhib?
prevents dopmaine breakdown
what are the mian side effects of levodopa?
dyskinesia - excessive motor activity from too much dopamine
what signs are seen in dyskinesia?
dystonia, chorea, athetosis
what is athetosis?
writhing/ twisting of wrists
what can be prescribed to help in dyskinesia from excess levadopa?
amantadine
