Lecture 7: Parkinson's Disease

Question 1

PD: Definition

Answer 1

• Progressive neurodegenerative disease
• Clinically: characterised by resting tremor, muscle rigidity and other non-motor impairments
• Pathologically: loss of dopaminergic neurons in the SNpc and presence of lewy bodies

Question 2

Prevalence

Answer 2

• second most com neurodegenrative disorder
• males more than females (evens out after menopause)
• 50-80 yrs onset

Question 3

Motor Symptoms

Answer 3

• Tremor at rest
• rigidity
• akinesia
• bradykinesia
• postural instability
  must have at least two of these symptoms, with one being tremor or bradykinesia

Question 4

Premotor symptoms

Answer 4

• hyposmia
• depression
• constipation
• sleep disturbances

Question 5

Cognitive changes

Answer 5

• Executive function
• Visuospatial function
• Can progress to parkinson’s disease-dementia

Question 6

Diagnosis

Answer 6

• no definitive tests (presents a significant problem as when symptoms present, ~80% of dopamine neurons are lost)
• relies on clinical symptoms, ruling out other diseases and levadopa response

Question 7

Risk factors

Answer 7

• age
• familial (5-10% have genetic cause)
• idiopathic 90-95%
  likely to be a mix of genetic and environmental causes

Question 8

Genetic mutations

Answer 8

• alpha synuclien
• UCHL1
• parkin

Question 9

Environmental factors

Answer 9

• history of TBI
• industrial chemicals
• pesticide and herbicide exposure
  Protective: tea, coffee and smoking

Question 10

Pathways

Answer 10

• Direct: promotes executive planned motor action by exciting cortical neurons
• Indirect: opposite
  These pathways are balanced for smooth execution of movement

Question 11

Dopamine and BG

Answer 11

• dopamine facilitates movement
• Reinforces activity of direct pathway
• reverses activity of indirect pathway
• results in excitation of cortical neurons and movement

Question 12

Lewy Bodies

Answer 12

• abnormal intracellular deposits of alpha-synuclein (thought to be involved in synaptic transmission usually)
• starts in BS then spreads throughout the cortex

Question 13

Other NT involved

Answer 13

• NA
• ACh
• 5HT

Question 14

Treatment

Answer 14

- No cure, just treat symptoms 
Levadopa
- Gold standard
- Dopamine cant cross BB, L-dopa is a precursor of dopamine 
- Over time becomes less effective

Question 15

SE of l-dopa

Answer 15

• acute: schizophrenia like symptoms, hypotension, weight loss
• long term: dyskinesia (abnormal movement): occurs in 80% of patients, gradually ineffective after several years