Etiology/Pathophys
Clinical Features
Diagnosis
Treatment
You Will Not Survive
100
This is the substantia nigra
What is B?
100
This is the earliest symptom of Parkinson disease
Bonus: name two additional pre-clinical symptoms
What is constipation?
Bonus: anosmia, REM sleep behavior disorder, restless leg syndrome, excessive daytime sleepiness
100
Parkinson disease is a...
What is a "clinical diagnosis"?
100
This inhibits DOPA decarboxylase to decrease peripheral side effects of L-DOPA
What are decarboxylase inhibitors (carbidopa, benserazide)?
100
A diagnosis of Parkinson disease is established with this
What is having two or more supportive criteria plus the absence of both red flags and absolute exclusion criteria?
200
Familial mutations in these genes are responsible for 10-15% of Parkinson disease cases (name 3 of 4)
What are alpha-synuclein (SNCA), glucocerebrosidase (GBA), dardarin (LRRK2), and parkin (PARK2)?
200
Motor signs usually present like this in Parkinson disease
What is unilateral or asymmetrical?
200
This is the function of MRI in diagnosing Parkinson disease
What is to rule out other possible diagnoses?
Note: imagine is not routinely required for diagnosis
200
This treatment is recommended for Px w/ severe motor symptoms
Bonus: what does it target?
What is deep brain stimulation?
Bonus: subthalamic nucleus or internal globus pallidus
200
This is a key buzzword for Parkinson disease (NOT "pill-rolling" tremor)
Bonus: how might this be described in a clinical vignette question stem?
What is "cogwheel rigidity"?
Bonus: described as passive motion eliciting a jerking-like motion; an overaly of increased muscle tonus and resting trmor
300
This class of drugs can cause drug-induced parkinsonism (secondary parkinsonism)
Bonus: why?
What are typical antipsychotics (e.g. haloperidol)?
Bonus: they have anti-dopaminergic effects
300
Parkinsons presentations can be remembered with the pneumonic:
"Parkinsonism TRAPs the Px", which stands for this
Tremor
Rigidity
Akinesia
Postural instability
300
This is a symptom of Parkinson disease
What is micrographia?
300
These block the conversion of L-DOPA to 3-O-methyldopa in the periphery
What are COMT inhibitors (entacapone, tolcapone)?
Extra: inhibits catechol-O-methyltransferase (COMT), tolcapone also inhibits COMT in the CNS (used in refractory Parkinson disease)
Extra: MAO-B inhibitors have a similar function in the CNS only to increase bioavailability of L-DOPA and thus decrease the demand
300
The pneumonic A2B2C2D2 can be used to remember the treatments available for Parkinson disease and it stands for this
What is:
A2: Anti-muscarinics and Amantidine
B2: Bomocriptine and MAO-B inhibitors
C2: COMT inhibitors and Carbidopa
D2: L-DOPA and nonergot Dopamine agonists
400
This is the function of dopamine in movement
What is it stimulates the direct pathway and inhibits the indirect pathway?
400
These are some neuropsychiatric symptoms associated with Parkinson disease (name 3)
What are depression, cognitive problems (develops in advanced disease), apathy, and behavioral changes (e.g. irritability and impulsivity)?
400
These are the supportive criteria for a Parkinson diagnosis (name 2)
What is a clear response to dopaminergic therapy, a resting tremor of a limb, and the presence of either olfactory loss or cardiac sympathetic denervation on MIBG scintigraphy
400
Nausea, vomiting, and orthostatic hypotension
What are the peripheral side effects of levodopa therapy?
Note: can be reduced with combination with decarboxylase inhibitors (carbidopa)
400
These are the absolute exclusion criteria for Parkinson disease (there are 9, since this is the evil category, name at least 5)
What are:
- Cerebellar abnormalities, including oculomotor dysfunction
- Downward vertical supranuclear gaze palsy or selective slowing of downward vertical saccades
- Diagnosis of probably frontotemporal dementia in first 5 years of disease
- Parkinsonism features restricted to lower limbs for 3+ years
- Treatment w/ a dopamine receptor blocker or a dopamine-depleting agent in a dose and time-course consistent w/ drug-induced Parkinsonism
- Absence of observable response to high-dose levodopa despite at least moderate severity of the disease
- Unequivocal cortical sensory loss, clear limb apraxia, or progressive aphasia
- Normal functional neuroimaging of the presynaptic dopaminergic system
- Potential alternative condition associated w/ Parkinsonism and plausibly connected to the patient’s symptoms
500
A 59yo woman comes to the physician because of worsening coordination and involuntary movements in her left hand for 6 months. Her husband reports that she has been withdrawn and apathetic during this period as well. Examination reveals a bimanual, rhythmic, low-frequency tremor in her left hand. ROM is normal in her arms and legs, however, active movements are slow and there is increased resistance to passive flexion and extension in the limbs. She walks with a shuffling gait and takes small steps. What is the pathophysiological cause of this patient's condition?
Neuronal degradation due to misfolded proteins such as alpha-synuclein (called Lewy bodies)
Note: While these misfolded proteins play a key role in Parkinson pathogenesis, the factors instigating neurodegeneration and loss of dopaminergic neurons are multifaceted and not well understood
500
A 67yo man comes to his physicians w/ worsening tremor that began one year ago. He also has a tremor in his left hand that improves when he uses it. He also reports feeling stiffer on a daily basis, and he has fallen twice in the past year. Further evaluation of this patient reveals reduced amplitude on foot tapping. Why?
Slowed and reduced amplitude on repetitive movements = bradykinesia (Hallmark feature of Parkinson disease)
Loss of dopaminergic neurons leads to a dopamine deficiency in the striatum, thus leading to a decreased excitatory signaling to the motor cortex (resulting in bradykinesia)
500
You found the free square!
+500
500
A 72yo woman comes to her physician because she is seeing things that she knows are not there. She also reports a lack of motivation to do daily tasks. Three years ago, she was diagnosed with Parkinson disease and was started on levodopa/carbidopa. Her younger brother has schizophrenia. She currently takes levothyroxine for hypothyroidism. Neurological exam shows mild resting tremor of her hands and bradykinesia. Her thought processes are organized and logical. What is the most likely cause of her symptoms?
Adverse effect of her Parkinson medication (levodopa/carbidopa)
Note: Overstimulation of D2 receptors in the CNS can lead to psychosis and hallucinations. This risk increases w/ age, other psychiatric conditions, and long duration and high concentrations of levadopa treatments.
500
A 55yo man comes to the physician with a 6 month history of worsening involuntary movement of his left hand. He reports that it takes him longer than usual to get up from a chair and that his symptoms are worse when he is stressed from work. Neurological examination shows difficulty initiating movement and a tremor in the left hand at rest. The tremor decreases when the Px is asked to draw a circle. What is the first-line therapy for treating this patient?
Px <65yoa w/ no significant comorbidities: nonergot dopamine agonists are often used as first-line therapy.
Note: Levodopa can also be used, but is associated with greater side effects such as drug-induced dyskinesias. Dopamine agonists have been shown to delay the onset of motor complications, and thus are often used as first-line therapy