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Flashcards in Parkinson's Deck (17)
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Prevalence & incidence of PD

- Prevalence 1% of the population above 65 years NL 100-150/100.000
- Incidence 5-25/100.000 NL 10/100.000

Man ≥ Woman
Diagnosis 50-70 years Onset typically between 50-60 years of age, and slowly progresses with age Average onset is 62.4 years of age


4 key symptoms of PD

•Tremor- Usually Tremor at rest and stops when person attemps to grab something
•Bradykinesia- Slowness in initiation and execution of voluntary Movements
•Rigidity- Increase of Muscle tone and resistance to movement
•Postural instability- abnormal fixation of posture, equilibrium


Additional motor symptoms of PD:

•Mask face
•Speech impairment


Non-motor symptoms of PD

•Cognitive dysfunction and dementia
•Psychosis and hallucinations
•Mood disorders (depression, anxiety)
•Sleep disturbances
•Autonomic dysfunction (constipation)
•Olfactory dysfunction
•Pain and sensory disturbances
•Dermatologic findings (seborrhea)


Two places of origin:

- substantia nigra
- ventral tegmental area


Idiopathic cell death in PD

•Abnormal protein formation Ubiquitine-proteasomal system
•Mitochondreal dysfunction Oxidative stress Excitotoxicity
•Genetic factors
•Immune system


Levels of striatal DA at the time that symptoms appear

Most symptoms do not appear until striatal DA levels decline by at least 70-80%


Description of Lewy bodies:

Morphology - Spherical 8-30 μm in diameter, eosinophilic
Central core: granular aggregates
Peripheral halo: fibrils and neurofilaments
Main constituent : α-synuclein


Features of Levodopa treatment:

•Dopamine precursor
Passage blood-brain barrier
COMT inhibitors: Block the action of Catechol-O-methyltransferase, an enzyme that breaks down dopamine
Entacapone or Tolcapone
•Periferal dopamine synthesis
Nausea, vomitus, orthostatic hypotension
Levodopa + Periferal decarboxilase inhibitor
•Motor on-off fluctuations
•Wearing off effect
•Hallucinations, psychosis, agitation


Dopamine agonists in PD (other than L-Dopa):

Direct stimulation dopamine receptors
 act LIKE dopamine at brain synapses where dopamine is usually present
Pergolide, pramipexol, ropinorol
Apomorfin (pump)

 Used both as adjuncts to L-Dopa therapy and in younger Parkinson’s disease patients
 Side effects similar to levodopa, but less likely to develop involuntary movements, more likely to cause hallucinations


Thalamotomy in PD

Involves destruction of small amounts of tissue in the thalamus—major center for relaying messages
Can cause slurred speech and lack of coordination


Pallidotomy in PD

electric current used to destroy small amount of tissue in the pallidum (globus pallidus)
May improve tremors, rigidity by interrupting pathway between globus pallidus and thalamus


Fetal Cell transplant therapy for PD

stem cells obtained via aborted fetus, grown in culture, transplanted into Parkinson’s patient at nigrostriatal pathway
New cells establish connections and “replace” cells originally lost, these cells function normally and even produce dopamine


Autologous "Self" transplant for PD

analagous to fetal cell transplant, except that precursor nerve cells are taken from patient and coaxed to produce dopamine, then implanted back into original patient
Reduces threat of autoimmune response associated with FCT therapy


Main toxic models of PD

- MPTP (monkeys/mice) (local infusion of MPP+ into the SNc or striatum)
- All the clinical symptoms which are also present in PD in monkeys. Efficient treatment with L-Dopa.
- 6-OHDA - 6-hydroxydopamine
-6-OHDA rat model mimics DA neuron loss and motor deficit
-Treatment L-DOPA and DBS STN efficient to improve motor deficit
(is a neurotoxic synthetic organic compound used by researchers to selectively destroy dopaminergic and noradrenergic neurons in the brain. 6-OHDA is thought to enter the neurons via the dopamine and noradrenaline (norepinephrine) reuptake transporters. Oxidopamine is often used in conjunction with a selective noradrenaline reuptake inhibitor (such as desipramine) to selectively destroy dopaminergic neurons only.)
- Rotenone
- Paraquat (Maneb)


Problems with toxic PD models

- -No progressive DA neuron loss
-No Lewy bodies
-Non-motor sympstoms are not present
Rotenone & Paraquat:
-Non-motor sympstoms are not present
-Variability in the individual response to the toxin


Transgenic PD models:

- alpha-synuclein (PARK1) - DA neuron loss & motor def., no LB-like inclusions
- UCHL (PARK5) - DA neuron loss and motor def.; no LB-like inclusions
- LRRK2 (PARK8) - same