Parkinson's Disease Flashcards
What is the second most common neurodegenerative disease?
Parkinson’s disease
What is the mean age of PD onset?
65
What are the most common risk factors for PD?
▪️ Male (1.5x)
▪️ Family history
▪️ Head injury
▪️ Pesticide exposure
What are the key motor symptoms of PD?
▪️ Tremor at rest
▪️ Rigidity (stiffness)
▪️ Bradykinesia (slowness)
▪️ Hypokinesia (poverty of movement)
What is the main motor indicator of early PD?
Unilateral signs and symptoms
How do the motor symptoms of PD changes as the disease progresses?
Become bilateral
What is the Hoehn and Yahr scale?
A measure of functional disability in PD
What are stages 1 and 2 on the Hoehn and Yahr scale?
Mild disability:
- Unilateral involvement with minimal or no functional disability
- Bilateral or midline involvement without impairment of balance
What is stage 3 on the Hoehn and Yahr scale?
Moderate disability:
▪️ Bilateral disease
▪️ Mild to moderate disability but physically independent
▪️ Impaired postural reflexes
What are stages 4 and 5 on the Hoehn and Yahr scale?
Severe disability:
- Severely disabling disease, still able to walk or stand unassisted
- Confinement to bed or wheelchair unless aided
What are some of the main non-motor symptoms of PD?
▪️ Neuropsychiatric/cognitive disorder
▪️ Sensory disorders
▪️ Medication-induced effects (e.g., ICD)
▪️ Urinary disorders and autonomic dysfunction
▪️ Fatigue and sexual dysfunction
▪️ Sleep disorder
▪️ Gastrointestinal disorders
What are the most common neuropsychiatric and cognitive symptoms of PD?
▪️ Psychosis (possibly drug-induced)
▪️ Depression
▪️ Anxiety
▪️ Apathy
▪️ Dementia
▪️ Hallucinations (particularly small children and animals)
What is DDS/ICD?
Dopamine Dysregulation Syndrome / Impulse Control Disorder
▪️ Behavioural problems resulting from prolonged use of dopaminergic medication such as L-DOPA
▪️ Characterised by increased gambling behaviours, hypersexuality, aggression, spending, binge eating etc
What symptoms in PD have the strongest correlation with quality of life?
Non-motor symptoms
What percentage of dopaminergic neurons are lost before motor symptoms become apparent?
50-70%
When is the prodromal stage of PD and what are the main symptoms?
Up to 20 years before motor symptoms
▪️ Hyposmia
▪️ Sleep disruption (e.g. RBD, loss of REM atonia)
▪️ Depression
▪️ Constipation
How long is the early motor stage of PD and what symptoms may become apparent?
3-6 years
▪️ Fatigue
▪️ Pain (subtle motor deficit?)
▪️ Diplopia (double vision)
How long is the mid stage of PD and what symptoms may become apparent?
4-12 years
▪️ Anxiety
▪️ Hypophonia (reduced speech intensity)
▪️ Dysphagia
▪️ Sleep disturbance (e.g., fragmentation)
How long is the late stage of PD and what symptoms may become apparent?
8 years
▪️ Dementia
▪️ Cognitive dysfunction
▪️ Hallucinations
▪️ Incontinence
▪️ Sexual dysfunction
▪️ Orthostatic hypotension (sudden BP drop when stand up)
What is the main pathological marker of PD?
▪️ Loss of dopaminergic neurons in the substantia nigra
▪️ Presence of Lewy bodies (abnormal accumulation of alpha-synuclein)
What are constant levels of dopamine necessary for?
▪️ Regulation of cortical excitation of striatal neurons
▪️ Stabilisation of the firing rate and excitability of striatal neurons
▪️ Modulations of plasticity of striatal neurons (LTP)
According to the Braak staging, where does Lewy body pathology start?
Olfactory bulb (explains prodromal hyposmia)
Where does the pathology spread to in the middle Braak stages?
▪️ Midbrain - substantia nigra (explaining onset of motor symptoms)
▪️ Neocortex
Where does PD pathology spread to in the late Braak stages?
Through the cortex (explaining cognitive dysfunction and dementia)
According to newer models of PD, what are the two subtypes?
▪️ Body-first PD
▪️ Brain-first PD
How is pathology proposed to spread in the body-first subtype of PD?
- Begins in gastrointestinal tract (explains constipation)
- Cardiovascular system and dorsal motor nucleus
- Locus coeruleus
- Substantia nigra
- Cortex
How does the brain-first PD subtype differ from the body-first subtype?
▪️ Begins in substantia nigra
▪️ Absence of classic non-motor prodromal phase
What other neurotransmitters may be involved in PD, contributing to the clinical heterogeneity?
▪️ Serotonin
▪️ Noradrenaline
▪️ Acetylcholine
What is required for the diagnosis of PD?
Motor symptoms - usually the triad of tremor, bradykinesia, and rigidity
What type of scan can be used to support PD diagnosis?
DaTSCAN
How does DaTSCAN work?
▪️ Radioactive nucleotide injected
▪️ Binds to dopamine transporters
▪️ Visualise using SPECT
▪️ Decreased binding in PD due to loss of dopaminergic neurons
What are the three things you can look for with a DaTSCAN?
▪️ Decreased binding indicating decreased dopamine uptake
▪️ Symmetry of decrease
▪️ Gradient - usually putamen lost first, followed by caudate
What percentage of PD patients have olfactory dysfunction?
70-100%
Typically underreported
Usually prodromal hyposmia but in same cases its late onset or complete anosmia
What can you use to test olfactory function?
UPSIT
(University of Pennsylvania Smell Identification Test)
What PD pathology likely underpins the increased prevalence of prodromal RBD?
Alpha-synuclein
What percentage of PD cases can be attributable to genetic mutations?
5-10%
What is the status of genetic testing in PD?
▪️ Not routine and costly
▪️ Presently unhelpful - no treatments that can be offered based on findings
▪️ May be inconclusive
▪️ Currently research based
What other degenerative disease may present with Parkinsonism?
▪️ Multiple System Atrophy
▪️ Progressive Supranuclear Palsy
What differential diagnoses should be consider when assessing for PD?
▪️ Other causes of parkinsonism (e.g., MSA, PSP, drug-induced, vascular, infections)
▪️ Tremor disorders (e.g., essential tremor, dystonic tremor)
If someone presents with only a tremor, what should you consider in diagnosis?
▪️ Essential tremor
▪️ Dystonic tremor
How might you distinguish essential tremor from PD?
▪️ Tremor not present at rest, only when performing action
▪️ Very symmetrical
(BUT can sometimes develop PD later so should observe patients carefully!)
What are the three main approaches to pharmacological treatment of PD?
▪️ Increase levodopa levels
▪️ Inhibit MAO and COMT enzymes to prevent dopamine breakdown
▪️ Dopamine receptor agonists
What are the three main options for the pharmacological treatment of PD?
▪️ Levodopa
▪️ Monoamine oxidase B inhibitor
▪️ Dopamine agonist
How do you choose which medication to use?
Personal preference based on side effects, comorbidities etc
(e.g., younger individual may prefer more potent treatment to function better)
What happens with levodopa therapy in the early stages of disease?
▪️ Smooth, long duration of benefit
▪️ Low incidence of dyskinesias (uncontrolled, erratic movements)
What happens with levodopa therapy in the mid-stage of disease?
▪️ Rapid onset of benefit due to more diminished dopamine stores
▪️ Diminished duration of benefit
▪️ Increased incidence of dyskinesias
▪️ Fall after peak dyskinesia
What happens with levodopa therapy in the advanced stage of disease?
▪️ Clinical response mirror levodopa plasma
▪️ Much shorter duration of benefit
▪️ ‘On’ time is associated with dyskinesias
▪️ Steep drop back to ‘off’ time
What motor complications are often seen in the later stages of disease?
Dopamine-induced motor fluctuations
“On/off” phenomena with dyskinesia (unstable PD)
What are the two key factors involved in the development of motor fluctuations?
▪️ Progressive degeneration - loss of ability to store dopamine and release it slowly
▪️ Pulsatile stimulation - typically take tablets three times daily, little we can do in between doses
What can we use to prevent motor fluctuations and development of dyskinesias?
Non-oral therapies and continuous drug delivery (CDD) (e.g., infusions)
What is the first-line option for continuous dopamine delivery?
Transdermal rotigotine
(Patch that releases dopamine continuously over 24 hours)
What more invasive options could be considered for CDD?
▪️ Subcutaneous apomorphine infusion (dopamine agonist in an insulin-like pump)
▪️ Intra-jejunal levodopa infusion (PEG, required surgery, patient can control dose)
Where are electrodes typically placed for the use of DBS in PD?
Subthalamic nucleus
