Neurotransmitters
________ is an excitatory neurotransmitter and ________ is an inhibitory neurotransmitter
Glutamate is an excitatory neurotransmitter and GABA is an inhibitory neurotransmitter
___________ is the most effective treatment for motor symptoms of Parkinson's disease, but is associated with time and dosage-dependent increase in dyskinesia
Levodopa
D2 receptors are used in the _______ pathway and ________ movement
D2 receptors are used in the indirect pathway and inhibit movement
True or False: Motor signs in Parkinson's disease are usually bilateral at onset and symmetrical
False! Motor signs are usually unilateral at onset (may progress to both sides) and asymmetrical (more pronounced on one side)
Neurodegenerative movement disorders are caused by damage to the _____________ leading to loss of inhibition of the thalamus and unwanted movements
basal gangloin
Surplus of this neurotransmitter (in the nucleus basalis of Meynert) likely causes the dyskinesia found in Parkinson's disease
Acetylcholine
Overstimulation of D2 receptors by levodopa or dopamine agonists may induce ______________, especially in older patients with concurrent dementia or other psychiatric disorders.
Psychosis and hallucinations
TRUE! L-DOPA, in contrast to dopamine, can cross the blood-brain barrier.
Parkinson disease is a clinical diagnosis, a definitive diagnosis requires postmortem confirmation of __________ found in substantia nigra, brainstem, and cortex.
Lewy bodies (aggregates of misfolded alpha-synuclein)
Wilson disease can cause neurologic symptoms when _______ accumulates in the _________
Bonus: What is the inheritance pattern for Wilson's disease.
Wilson disease can cause neurologic symptoms when copper accumulates in the CNS (basal ganglia, brain stem, cerebellum).
Bonus: Autosomal Recessive
Depletion of these two neurotransmitters (found in the ralph nuclei) likely cause depressive symptoms in Parkinson's patients.
Serotonin and noradrenaline
mechanism of action of this drug is to prevent the peripheral conversion of levodopa to dopamine, which reduces the side effects of levodopa and increases the amount of levodopa available to the brain
Decarboxylase Inhibitors (Carbidopa)
What are the cardiovascular effects of dopamine?
Raises BP (at high doses), HR, and Cardiac Output
Approximately ____ % of Parkinson's cases have a family history for this disorder.
Bonus for +100 pts, why might Canadians be at increased risk of developing Parkinson's disease?
Approximately 10-15% of Parkinson's cases have a family history for this disorder.
Familial cases of Parkinson's disease can be caused by mutations in the LRRK2, PARK7, PINK1, PRKN, or SNCA gene
Bonus: low levels of Vitamin D are a risk factor (also: exposure to manganese, high iron intake, and hx of traumatic brain injury).
Parkinson's disease is caused by the loss of ________ neurons found in the ___________.
Huntington's disease is caused by the loss of _______ found in the __________.
Parkinson's disease is caused by the loss of dopaminergic neurons in the substantial nigra pars compact (leads to depigmentation).
Huntington's disease is caused by the loss of GABAergic neurons found in the striatum (striatum= caudate+putamen).
Huntington's Disease is associated with ____ dopamine, ______ GABA, and ____ ACh in the brain.
Huntington's disease is associated with increased dopamine, decreased GABA, and decreased ACh in the brain.
__________ is the drug of choice for akinetic crisis (severe dopamine deficiency) and acts by __________ the NMDA receptor which increases dopamine release and decreases dopamine reuptake in the central neurons.
Amantadine is the drug of choice for akinetic crisis (severe dopamine deficiency) and acts by antagonising the NMDA receptor which increases dopamine release and decreases dopamine reuptake in the central neurons.
PD is a result of dopaminergic neuron degeneration in the substantial nigra leading to dopamine deficiency. Which pathway (direct or indirect) of the basal ganglia is affected?
Indirect Pathway
Name 3 signs of pre-clinical stage PD
Pre-clinical stage:
Constipation
Anosmia
Mood disorder
Sleep Disturbances (REM sleep behavior disorder, restless leg syndrome, excessive daytime sleepiness)
Hemiballism is usually caused by a __________
Hemiballism is usually caused by a stroke that affects the subthalamic nucleus.
Hemiballismus is a hyperkinetic involuntary movement disorder characterized by intermittent, sudden, violent, involuntary, flinging, or ballistic high amplitude movements involving the ipsilateral arm and leg caused dysfunction in the central nervous system of the contralateral side
Glutamate is called an excitotoxin because it can cause nerves to become overexcited and lead to _________
Brain cell damage or death
In deep brain stimulation, stimulating electrodes are implanted and target _____(name 1 of the 2 structures)
Subthalamic nucleus and internal globus pallidus
_________ breaks down dopamine into DOPAC. _________ drug class inhibits this enzyme which results in decreased dopamine metabolism in the brain.
MAO-B (Monoamine Oxidase B), MAO-B inhibitors (selegiline, rasagiline)
True or False: Pharmacotherapy DOES alter the disease trajectory in PD, and treatment should be initiated early to improve prognosis
False: Pharmacotherapy DOES NOT alter the disease trajectory in PD; initiate when symptoms interfere with quality of life.
List 4 motor and 3 non-motor signs of Parkinsons
Motor:
Parkinsonism, Bradykinesia (slowed movements), Resting tremor, Rigidity, Postural instability, Gait problems, Many others (glabellar reflex, microphagia, etc)
*Parkinsonism is required for the diagnosis of Parkinson disease.
Non-motor:
Autonomic symptoms, Neuropsychiatric symptoms, disordered sleeping, Anosmia