AC - Parkinson's Disease

Question 1

What are the cardinal features of parkinson’s disease?

Answer 1

1. Hypokinesia/bradykinesia
2. Resting tremor
3. Increased tone/rigidity

Question 2

What are some features of hypokinesia/bradykinesia?

Answer 2

Micrographia
Reduced facial expression - masked fascies
Reduced blinking 
Monotomous speech 
Gait abnormalities

Question 3

What are the features of a parkinsonian gait?

Answer 3

Reduced arm swing
Hesitancy initiating gait 
Freezing at obstacles 
Pedestal turning 
Festination - increaseing velocity of gait with reducing stride length 
Leaning forward
Shuffling gait

Question 4

What are features of the resting tremor & increased tone?

Answer 4

Resting tremor usually improves slightly with movement, often worse on one side. Hx of dropping things or difficulty with fine movement

Increased tone associated with cog-wheeling and contributes to impaired gait

Question 5

What are other features of parkinson’s?

Answer 5

Depression, dementia 
Visual hallucinations 
Sleep disturbance 
Anosmia 
constipation 
Postural instability - hx of falls 
Autonomic dysfunction - orthostatic hypotension, labile BP, urinary incontinence/urgency/frequency

Question 6

What are common early signs of PD?

Answer 6

Impaired smell, urinary changes and constipation

Question 7

What is the basic pathophysiology of PD?

Answer 7

Destruction of dopaminergic neurones in the Substantia nigra - 80% destruction before symptomatic
Results from mitochondrial DNA dysfunction, ubiquitan-protease system and alpha-synuclein misfolding

Question 8

What are the pharmacological Rx options for PD?

Answer 8

1. Increase dopamine synthesis - Levodopa
2. Dopamine receptor agonist - Cabergoline
3. Dopamine breakdown inhibitors - COMT inhibitors, MOAB inhibitors (Selegiline)

Question 9

Describe features of Levodopa & use in PD Rx

Answer 9

Levodopa is precursor to dopamine - can’t use dopamine as strong emetic agent
Use in conjunction with peripheral conversion inhibitor (Carbidopa) to reduce side effects
Requires some dopaminergic neurons to work but can accelerate their destruction - debate about timing of commencement
Decreased effectiveness with long term use - require higher doses, results in weaning off effect and motor fluctuations

Question 10

What are the side effects of levodopa & effects of decreased effectiveness?

Answer 10

N+V, headache, visual hallucinations, confusion, orthostatic hypotension, arrhythmias

Weaning effect - pronounced end of dose reduced effect. Can lead to acute akinesia

Motor fluctuations - failure to turn ‘on’ (state of symptom control) or unpredictable fluctuations b/w ‘on’ / ‘off’ state

Overmedication - leads to EPSE - dystonia (involuntary muscle spasms i.e. of eyes, larynx), dyskinesia (abnormal movements similar to chorea)

Question 11

What medication is preferred in younger patients?

Answer 11

Dopamine receptor agonists - cabergoline
Can be used as monotherapy
Similar side effects to levodopa but more pronounced visual hallucinations & pulmonary/cardiac fibrosis