parkinson's

Question 1

symptomatic hallmarks of movement disorders

Answer 1

• tremor
• athetosis
• chorea
• dystonia
• tics

Question 2

athetosis

Answer 2

slow movements, twisting and writing

Question 3

chorea

Answer 3

brief, jerky, rapid, unpredictable movements

Question 4

dystonia

Answer 4

sustained muscle contraction
repetitive movements

Question 5

tics

Answer 5

sudden repetitive, non-rhythmic motor movement

Question 6

synucleinopathy

Answer 6

• mutation of alpha-synuclein > duplication/triplication of normal alpha-synuclein gene
• mutation of leucine-rich repeat kinase-2-gene (LRRK2) > autosomal dominant familial parkinsonism
• mutation in parkin gene > early onset; autosomal recessive familial parkinsonism

Question 7

risk factors

Answer 7

high risk;
- pesticides (rotenone)
- environmental or endogenous toxins
- vitamin D deficiency
- people working in teaching, health care, farming, exposed to lead or manganesse

low risk;
- cigarette smokers
- coffee
- anti-inflammatory disease
- high serum uric acid levels.

Question 8

progression of PD
Braak stages

Answer 8

1. olfactory nucleus, lower brianstem
2. higher brainstem
3. substantia nigra
4. mesocortex and thalamus
5. entire neocortex

Question 9

symptom classification

Answer 9

1. symptoms only on 1 side
2. symptoms on both sides, NO balance problems
3. symptoms on both sides, balance problems, patients can still function independently
4. symptoms on both sides, balance problems, patients need daily help
5. severly disabled state; nursing care

Question 10

hallmarks of PD

Answer 10

• cell death in dopaminergic neurons; less dopamine available
• lewy bodies with a-synuclein aggregation in the cell body of neurons

Question 11

extracellular a-synuclein

Answer 11

interacts with microglia and astrocytes, release of cytokines, which affects other neurons.

Question 12

dopamine pathways

Answer 12

• nigrostriatal pathway
• mesolimbic pathway
• mesocortical pathway
• tuberohypophyseal pathway

Question 13

dopamine synthesis and metabolism

Answer 13

tyrosine > dopa > dopamine

metabolized by MAO and COMT

Question 14

dopamine receptors

Answer 14

D1 - D1, D5
Gs activation > increase cAMP and PK
stimulation of AMPA-, NMDA-receptor and L-Ca2+-channels.

D2 - D2, D3, D4
Gi activation > decrease cAMP, increase K+ channel conductivity
pre and postsynaptic inhibition

Question 15

functional aspects

Answer 15

• motor control > nigrostraital system
  antipsychotic drugs are D2 antagonist, blocking D2 in mesolimbic pathway
• behavioral aspects > mesolimbic and mesocortical system
  amphetamine releases both dopamine and noradrenaline
• endocrine control > tuberohypophyseal system
  dopamine inhibits prolactin secretion and promote growth hormone production
• vomiting, nausea
  dopamine agonists induce nausea
  D2 receptors associated with initiation of nausea

Question 16

direct basal ganglia pathway

Answer 16

cause movement, thalamus is activated
substantia nigra is inhibited, less GABA to the thalamus, thereby LESS inhibition, causing movement

Question 17

indirect basal ganglia pathway

Answer 17

no movement, thalamus is inhibited
by activation of globus, more GABA to thalamus, inhibited > no movement

Question 18

therapy

Answer 18

• restore dopamine activity;
  levodopa, dopamine agonists, MAO-B inhibitors, COMT inhibitors.
• restoring balance between cholinergic and dopaminergic system
• blocking acetylcholine

Question 19

levodopa

Answer 19

can cross the BBB, metabolised in the brain by D1-3 receptors to dopamine.
» source of dopamine, restoring dopamine activity
in combination with carbidopa 10% in brain

Question 20

dopamine receptor agonists

Answer 20

increase the uptake of dopamine
do not compete for active transport into the blood and across the BBB
first in line therapy

bromocriptine; D2 agonist
pergolide; D1 and D2 agonist
pramipexole; D3 agonist
ropinirole; D2 agonist
rotigotine;

Question 21

MAO inhibitors

Answer 21

blocks the metabolism of dopamine, increasing dopamine levels

selegiline
rasagiline; early treatment

Question 22

COMT inhibitors

Answer 22

inhibition of DOPA decarboxylase leads to upregulation of other pathways;
COMT turns dopamine into 3-OMD, 3-OMD competes with L-DOPA for transport proteins to cross BBB.

tolcapone
entacapone
» prolong actions of levodopa

stalevo; combination of tolcapone, entacapone and levodopa

Question 23

other procedures

Answer 23

surgery
neuroprotection
gene therapy
drug-induced PD