Dont pick me
What are the symptoms associated with Parkinson's? What is the general age of onset?
Pill Rolling tremor (at rest), Shuffling gait, trouble imitating movement, Cogwheel rigidity
What are ways of lifestyle management for PD?
Exercise is the big one, keeps the Substantia Nigra more active, anti-oxidant foods
Main drug to treat PD that is gold standard and its MOA
Bonus-what enzyme is this related too
L-Dopa/Carbidopa, works since it increases metabolite that can be converted to dopamine via Dopa Decarboxylase
Researchers are working with hippocampal neurons and stimulate action potential of these cells.
This graph is shown:
What neurotransmitter is this likely showing the activity of?
A. Dopamine
B. Norepinephrine
C. acetylcholine
D. Glutamate
E. GABA
D. Glutamate
Glutamate is highly active in Hippocampus as well as Acetylcholine, but this shows an action potential activation so its Glutamate
How do you clinically diagnose Parkinson's disease and who can do so? How can you identify the severity of the disease?
Psychiatrists, Neurologists, Neurosurgeons
UPDRS-Unified Parkinson's Disease Rating Scale
Mild, Moderate, Severe
Mild (0-32), 33-58, 59+ Severe (for motor part only)
Why is it important to closely monitor L-Dopa/Carbidopa levels?
Side effects are strong for L-Dopa and also this leads to a less natural L-Dopa, which leads to worsening of symptoms since our body stops naturally making L-Dopa
How does Deep Brain stimulation work and why is it used as an alternative?
Implant that conducts an AP with high energy that leads to inhibition of GPi and STN that lead to stimulation of Thalamus
How does L-Dopa lead to heart problems? Why do you give it with Carbidopa for this reason?
L-Dopa leads to an increase in the metabolite of Dopamine, although this is converted to dopamine to help in the CNS, it is done peripherally also.
Dopamine on the heart leads to increased cardiac function and stress on the heart
Carbidopa inhibits peripheral decarboxylase so dopamine is not overly increased in the periphery
Acetylcholine is increased, Dopamine and Serotonin are decreased
What is seen histologically with Parkinson's disease and why how does it lead to dysfunction
Lewy bodies that contain alpha-synuclein aggregate in mitochondria and lead to dysfunction; smaller aggregates within the mitochondria lead to cell apoptosis
Play patient and doctor and act out a neurological exam for a PD patient
Based on group agreement
Why is depression so commonly seen in PD patients?
Two reasons
Decrease in dopamine/reward pathway
difficulty handling diagnosis
Why are COMT inhibitors effective? Give an example of this drug. Give an adverse effect
Entacapone (PNS) and Tolcapone (CNS and PNS);
Inhibit COMT which is supposed to breakdown dopamine; increases level by keeping the neurotransmitter longer
Tolcapone is very hepatotoxic
PD affects 1 to 2 people per 1000 at any time; the prevalence increases with age to affect 1% of the population above 60 years. 5% to 10% of patients have a genetic predisposition. The incidence and prevalence of PD do increase with advancing age; the condition is more common in men than women.More common in caucasians
Risk factors for PD; name some genes
Genetics, age, race
Genes include-
What is a side effect of Selegiline and how does this drug work?
Inhibits MAO-b which breaks down Dopamine more than serotonin; this can lead to serotonin buildup which can lead to serotonin syndrome which can lead to hypertensive syndrome
Board question
D.
What is the pathophysiology of PD? How does this lead to tremor
Destruction of Substantia Nigra Pars Compacta leading to loss of dopaminergic neurons which also leads to a dysregulation of basal ganglia function like globus pallidus interna and STN
Loss of dopamine means there is deregulation of direct and indirect pathway;
What is the function of the globus pallidus interna and why is does it matter?
Leads to release of GABA that functions on the thalamus. Thalamus is the main regulator for motor and sensation. If thalamus is inhibited, movement becomes less regulated
Expected MRI findings in PD
Specific brain MRI findings associated with PSP include atrophy of the midbrain with enlargement of the third ventricle, tegmental atrophy and an abnormal superior profile of the midbrain, signal increase in the midbrain and in the inferior olives, as well as frontal and temporal lobe atrophy
What are the functions of Synaxtin-1 and SNAP-25 and why does this matter in PD?
Synaxtin-1 and SNAP-25 are SNARE proteins. SNARE proteins are important in the function of exocytosis of the vesicle containing neurotransmitters.
Dysfunction of these is a reason why you have a decrease in neurotransmitters
Explain what how PD affects the brain to a 10-year-old
I will decide if ya get points
Outline the basal ganglia pathway for direct and indirect pathway
Image
Why is Synaptobrevin and how does it affect vesicles?
Synaptobrevin attaches to the vesicle and helps it reach the synaptic terminal so that SNAP-25 and other SNARE proteins can help lead to eventual neurotransmitter release
How does STN play a part in PD?
In Parkinson’s disease, the loss of dopamine input to the striatum (the input region of the basal ganglia) leads to a cascade of effects on the STN: