Flashcards in Parkinson's Disease and Movement Disorders Deck (61)
Prognosis of Parkinson's post-diagnosis
10-20 years post-diagnosis
What does Parkinsonism mean?
the person has PD-like symptoms, but can be induced by other means, such as antipsychotics
When does Parkinson's disease usually present?
in the 60s-70s, but 5-10% present before age 40
Where is the neurological deficit with Parkinson's disease?
deficit in the extrapyramidal system
chronic, progressive, irreversible disease, leading to tremor and muscular rigidity
Parkinson's disease symptoms
resting tremor; akinesia; muscular rigidity; compromised cognitive functions; comorbid depression (25% of pts)
Describe the rigidity of Parkinson's disease
flexors and extensors both contracted, so pts often quite fatigued
Pathophysiology of PD
cell death in the substantia nigra; decreased DAergic innervation in the basal ganglia
Structures in the basal ganglia (striatum)
caudate nucleus; putamen; globus pallidus; terminal projection fields from the SNc
What does the striatum do?
striatum allows a movement to occur, so damage to normal excitation/inhibition circuitry will disturb normal execution of movements
What kind of circuits are the direct and indirect pathways?
Reduced direct pathway activity causes
greater inhibition of GPe; GPe is inhibitory, so this results in less inhibition of STN
What does increased activity of STN contribute to
overactivity of GPi/SNr
Increased activity of GPi/SNr causes
causes increased inhibition of the thalamus
What happens when thalamus activity is decreased/?
results in reduced motor commands from cortex, resulting in the motor symptoms of PD
What does the thalamus normally do?
thalamus is excitatory and normally provides activation of the cortex to allow execution of motor commands from the basal ganglia
Etiology of PD
2. Environmental factors (pesticide exposure)
3. Redox hypothesis
4. Genetic factors (familial, parkin, LRRK2, alpha-synuclein)
DA toxic, oxidized, creates ROS and oxidative stress to DA neurons - which may be particularly vulnerable to this stress
What is the correlation between smoking and Parkinson's Disease?
inverse correlation between smoking and PD, which has been theorized to result from nicotine in cigarettes; independent of smoking's harmful health effects and dose-dependent
Rate-limiting enzyme in DA production
What does the L-dopa approach rely on
relies on the remaining, live DA neurons to produce increased amounts of DA
1. Pramipexole (Mirapex)
2. Ropinirole (Requip)
3. Rotigotine (NeuroPro)
Used to mimic the action of DA in the indirect pathway
DA D2 and D3 agonists
Carbidopa is an inhibitor of
peripheral L-dopa metabolism, which helps to direct a greater percentage of the L-dopa to the CNS and allows the dose of L-dopa to be reduced
What does reducing the dose of L-dopa help with?
helps to reduce the onset of dyskinesias and reduces other side effects like GI problems
What enzyme does Carbidopa inhibit?
L-aromatic amino acid decarboxylase
What is Sinemet?
Levo-dopa + Carbidopa
Positive aspects of Sinemet
better survival; bradykinesia and rigidity improved; mood improvement
Problems with Sinemet
decreased prolactin; increased GH; arrhythmias; postural hypotension; nausea initially