7 - Parkinson's Disease

Question 1

what are the core clinical features of PD?

Answer 1

• bradykinesia + rigidity
• resting tremor

Question 2

is tremor always present in PD?

Answer 2

no - absent in 30%

Question 3

what genetic factors can result in PD?

Answer 3

• recessive genes - parkin
• dominant genes - SNCA
• dysfunction in cellular pathways

Question 4

what are environmental factors that can result in PD?

Answer 4

• toxins - paraquat (herbicide commonly used in rural USA)
• ? spread of toxic/infective agents from gut/olfactory systems

Question 5

what are the diagnostic criteria for PD?

Answer 5

• bradykinesia + tremor and/or rigidity
• absence of red flags
  at least one of:
• clear response to dopaminergic therapy
• levodopa-induced dyskinesia
• rest tremor
• olfactory loss

Question 6

list 4 red flags for PD diagnosis

Answer 6

• symmetrical onset
• early gait abnormality and falls
• pyramidal tract signs
• poor levodopa response
• supranuclear gaze palsy
• early dementia

Question 7

early gait abnormality, supranuclear gaze palsy, and early dementia would be red flags for PD - what may they be indicative of instead?

Answer 7

PSP - progressive supranuclear palsy

Question 8

dysautonomia (disorder of involuntary functions), ataxia (disorders of coordination, balance and speech) and stridor (inspiration + expiration) are red flags for PD - what are they indicative of instead?

Answer 8

MSA - multiple system atrophy

Question 9

apraxia (loss of ability to carry out skilled movement), myoclonus (twitching of muscles), alien limb (hand acts independently) are red flags for PD - what may they be indicative of instead?

Answer 9

CBS - corticobasal syndrome

Question 10

what are possible pre-motor symptoms in PD?

Answer 10

• REM sleep behaviour disorder - act out dreams during night
• anosmia - loss of sense of smell
• constipation
• depression
• pain

Question 11

what is the typical age of onset of PD?

Answer 11

• > 60
• young onset - (<40) in 5%

Question 12

what is the mechanism of bradykinesia?

Answer 12

• increased inhibitory output to brainstem
• increased inhibitory output to thalamus and motor cortex

Question 13

bradykinesia is associated with abnormal oscillations in basal ganglia circuits - what abnormal frequency is this?

Answer 13

20Hz

Question 14

when is rigidity most obvious?

Answer 14

during slow movements

Question 15

when is spasticity most obvious?

Answer 15

during velocity-dependent movements

Question 16

what is the pathophysiology of rigidity in the periphery?

Answer 16

• reduced inhibition from type Ib fibres
• overactive type II fibres
• increased activity due to peripheral stimulation

Question 17

what is the pathophysiolofy of rigidity in the central system?

Answer 17

• altered GABA and ACh activity in interneurons
• altered inhibition in indirect pathway

Question 18

tremor is absent in roughly what % of PD pts?

Answer 18

30

Question 19

is tremor more or less responsive to dopaminergic drugs?

Answer 19

less

Question 20

where is tremor initiated? what brain region amplifies tremor activity?

Answer 20

initiated - basal ganglia
amplified - cerebellar-thalamo-cortical loops

Question 21

what drugs are commonly used to treat tremor?

Answer 21

rasagiline

Question 22

why isn’t dopamine given directly to treat PD?

Answer 22

it doesn’t pass the BBB - hence why it’s given as L-dopa

Question 23

why are dopamine agonists less preferred than levodopa?

Answer 23

• more adverse effects
• impulse control disorders
• withdrawal problems

Question 24

what are two motor complications in PD?

Answer 24

• wearing-off and motor functions
• L-dopa-induced dyskinesia

Question 25

what are the mechanisms of motor complications in PD?

Answer 25

• there is pulsatile dopaminergic stimulation
• serotonin neurones try to compensate for lack of DA neurones
• not specialised for this = abnormal handling
• = abnormal synaptic plasticity

Question 26

what are 4 impulse control disorders associated with PD?

Answer 26

• pathological gambling
• hypersexuality
• compulsive shopping
• binge eating

Question 27

what are some risk factors for impulse control disorders related to PD?

Answer 27

• dopamine agonist use>levodopa
• smoking
• male
• young-onset PD
• depression
• family history of gambling or alcoholism

Question 28

abrupt withdrawal of PD medications can result in what?

Answer 28

neuroleptic malignant syndrome

Question 29

what is neuroleptic malignant syndrome?

Answer 29

• high fever
• stiffness of muscles
• altered mental state (paranoid behaviour)
• autonomic dysfunction (causes wide swings of BP, excessive sweating, excessive salivary production)

Question 30

what are 2 later stage PD symptoms?

Answer 30

• axial symptoms
• dementia, psychosis

Question 31

what are ‘axial’ symptoms in PD?

Answer 31

• falls, gait disturbance
• high risk of fractures
• dysphagia, speech disturbance
• generally poor levodopa response

Question 32

what medications can help with dementia and psychosis related to PD?

Answer 32

rivastigmine

Question 33

how do SPECT scans work?

Answer 33

single photons registered by rotating gamma camera

Question 34

how do PET scans work?

Answer 34

two gamma-rays emitted at 180 degrees detected by static rings of detectors

Question 35

what is the main difference between SPECT and PET scans?

Answer 35

SPECT - low cost, poor resolution, long tracer half life
PET - higher cost, better resolution

Question 36

fluorodeoxyglucose is a measure of what?

Answer 36

marker of synaptic activity in the brain

Question 37

fluorodopa binds to what in the brain?

Answer 37

bind to vesicles containing dopamine