Parkinson's Disease

Question 1

What are the 4 cardinal signs of Parkinson’s?

Answer 1

(1) asymmetric resting tremor (4-6 Hz tremor observed in a fully resting limb that is suppressed when initiating movement), (2) bradykinesia (slowness of movement/difficulty initiating movement and decreased speed as movements are continued), (3) rigidity (lead-pipe resistance to passive movement), and (4) gait disturbance/hypokinesia (partial or complete loss of muscle movement due to disruption in basal ganglia)

Question 2

What is the pathophysiology of Parkinson’s?

Answer 2

destruction of dopaminergic neurons in the brain stem (particularly the substantia nigra) leading to development of dopamine deficiency and the development of Lewy Bodies

Question 3

What is the primary defect in Parkinson’s?

Answer 3

loss of dopamine in the corpus stratium (the caudate and lentiform nuclei)

Question 4

What is the pathological hallmark of Parkinson’s?

Answer 4

Lewy bodies - abnormal aggregates of protein (alpha-synuclein) that develop inside nerve cells - definitive diagnosis but only seen on autopsy

Question 5

What is the substantia nigra?

Answer 5

brain structure located in the mesencephalon (midbrain) that plays an important role in reward and movement - parts of the substantia nigra appear darker than neighboring areas due to high levels of neuromelanin in dopaminergic neurons

Question 6

When do symptoms of Parkinson’s appear?

Answer 6

when 70-80% of dopaminergic neurons have died

Question 7

What is Parkinsonism?

Answer 7

any of a group of nervous system disorders with symptoms similar to Parkinson’s Disease

Question 8

How is clinically established Parkinson’s diagnosed?

Answer 8

presence of parkinsonism, no absolute exclusion criteria, at least 2 supportive criteria, and no red flags

Question 9

What are supportive factors for a diagnosis of Parkinson’s?

Answer 9

unilateral onset, masked facies (decline in spontaneous facial expression), hypophonia (soft speech)/monotone, gait disorder/falls, flexed posture (forward tilt of trunk, reduced arm swinging, shuffling gate), persistent asymmetry

Question 10

What is bradykinesia?

Answer 10

generalized slowness of movement, starts distally (in arms with decrease in manual dexterity of fingers), progresses to dragging of legs/shuffling gait

Question 11

How does tremor present in Parkinson’s?

Answer 11

unilateral resting tremor (not engaged in purposeful activities) - can be intermittent

Question 12

How does rigidity present in Parkinson’s?

Answer 12

increased resistance to passive movement, often begins unilaterally

Question 13

What is cogwheel rigidity?

Answer 13

ratchet pattern of resistance and relaxation

Question 14

What is leadpipe rigidity?

Answer 14

an increase in muscle tone causes a sustained resistance to passive movement throughout the whole range of motion, with no fluctuations - test by grasping elbow at antecubital region and flexing/extending or pronating/supinating the forearm

Question 15

What is the common hand motion associated with Parkinson’s?

Answer 15

pill rolling of hand

Question 16

What is the “pull test”?

Answer 16

giving a firm pull on the shoulders from behind the patient to check postural reflexes - normal = maintain balance or take only one step; loss of reflexes = multiple steps/fall

Question 17

What are the craniofacial motor features of Parkinson’s?

Answer 17

hypomimia (masked facial expression), decreased spontaneous eye blink, sialorrhea (excessive salivation)

Question 18

What are some red flags that could suggest a diagnosis other than Parkinson’s?

Answer 18

rapid progression of gait impairment, absence of progression of motor symptoms, early bulbar dysfunction (speech and swallowing), impaired inspiration, severe autonomic failure in the first 5 years, recurrent falls, repetitive anterocollis (neck flexion), bilateral symmetric parkinsonism, poor response to Levodopa

Question 19

What is a positive dopaminergic challenge test?

Answer 19

clinically significant improvement (15-30% or more) in the Unified Parkinson Disease Rating Scale one hour after a dose of levodopa or 20 minutes after sub-Q apomorphine - absence of an observable response to high-dose levadopa (1000-1500 mg daily for at least 2 months) makes the diagnosis of Parkinson’s extremely unlikely

Question 20

What is the first-line treatment for Parkinson’s?

Answer 20

Levodopa or carbidopa-levodopa (sinemet or madopar - 10/100, 25/100, 25/250 mg) - start low and titrate up - avoid taking with high protein meals - most effective in treating bradykinetic symptoms - titrate to lowest dose that produces useful clinical response (300-600 mg of levadopa/day)

Question 21

What are some additional pharmacological treatments for Parkinson’s?

Answer 21

dopamine agonists, monoamine oxidase (MAO) B inhibitors, antichlinergic agents, amantadine, catechol-O-methyl transferase (COMT) inhibitors

Question 22

What are some side effects of levodopa?

Answer 22

nausea (take with food early in treatment), somnolence, dizziness, headache, confusion, hallucinations, delusions, agitation, psychosis, orthostatic hypotension

Question 23

What is carbidopa?

Answer 23

a peripheral decarboxylase inhibitor that blocks conversion of levodopa to dopamine within the systemic circulation (more dopamine is able to cross the blood/brain barrier) - helps prevent nausea, vomiting, and orthostatic hypotension

Question 24

What is the mechanism of action of dopamine agonists (bromocriptine/Parlodel, pramipexole/Mirapex, ropinirole/Requip) in Parkinson’s?

Answer 24

stimulate dopamine receptors (will be ineffective in patients with no response to levadopa) - can be used a adjunct to levodopa or as monotherapy - more beneficial in younger patients (AE: hypotension, cardiac dysfunction, nausea/vomiting, peripheral edema, impulse control disorders) - use as first-line treatment for patients < 65 years old, dosage: 2-6 mg TID

Question 25

What is the mechanism of action of MAO B inhibitors (selegiline - 5 mg daily, rasagiline - 1 mg daily) in Parkinson’s?

Answer 25

delays destruction of neurons and inhibits metabolic breakdown of dopamine (AE: nausea, headache, insomnia, confusion, enhanced levodopa AEs)

Question 26

What is the mechanism of action of anticholinergics (trihexyphenidyl/Artane - 0.5-1 mg BID; benztropine/Cogentin - 0.5-2 mg BID) in Parkinson’s?

Answer 26

block the action of acetylcholine, a chemical messenger that helps to send messages from your nerves to your muscles - tend to improve tremor more than slowness and stiffness (AE: confusion, hallucinations, dry mouth, blurred vision, constipation, urinary retention, tachycardia)

Question 27

What is the mechanism of action of amantadine (Symmetrel/Symadine - 200-300 mg/day) in Parkinson’s?

Answer 27

unknown - antiviral medication - useful for akinesia and rigidity (AE: livedo reticularis [mottled skin], ankle edema)

Question 28

What is the mechanism of action of COMT inhibitors (entacapone/Comtan - 200 mg with each dose of levodopa up to 8 doses per day; tolcapone/Tasmar - 100 mg TID) in Parkinson’s?

Answer 28

ineffective when given alone - increases the plasma half-life of levodopa - mainly used to treat motor fluctuations (AE: dyskinesia, hallucinations, confusion, nausea, orthostatic hypotension) - mainly used for patients experiencing “wearing off” periods

Question 29

What is deep brain stimulation?

Answer 29

implantation of a battery-operated medical device that delivers electrical stimulation to targeted areas of the brain to block abnormal nerve signals that cause tremor and Parkinson’s symptoms

Question 30

What is Parkinson disease?

Answer 30

a chronic, progressive neurodegenerative disorder characterized by 4 cardinal signs - at a minimum, bradykinesia and tremor or rigidity must be present - beneficial response to dopamine is supportive of the diagnosis

Question 31

What is the “gold standard” for diagnosis of Parkinson’s disease?

Answer 31

neuropathological examination (can only be done on autopsy)

Question 32

What are red flags in the diagnosis of Parkinson’s disease?

Answer 32

potential signs of alternate pathology: rapid progression of gait impairment, absence of progression of motor symptoms over 5 years or more, early bulbar dysfunction (severe dysphona, dysarthria, or dysphagia) within first 5 years, inspiratory dysfunction, severe autonomic failure (orthostatic hypotension, urinary retention/incontinence) in first 5 years, recurrent falls, contractures of hand/feet, absence of nonmotor symptoms, pyramidal tract signs, bilateral symmetric parkinsonism

Question 33

What are the criteria for clinically established Parkinson’s?

Answer 33

presence of parkinsonism, no absolute exclusion criteria, at least two supportive criteria

Question 34

What are supportive criteria of the diagnosis of Parkinson’s?

Answer 34

clear response to dopaminergic therapy, presence of levodopa-induced dyskinesia, rest tremor of a limb, presence of olfactory loss or cardiac sympathetic denervation

Question 35

What are the criteria for clinically probable Parkinson’s?

Answer 35

presence of parkinsonism, no absolute exclusion criteria, presence of red flags is counterbalanced by supportive criteria (no more than 2 red flags allowed)

Question 36

What is parkinsonism-hyperpyrexia syndrome?

Answer 36

neuroleptic malignant syndrome in the context of sudden withdrawal or dose reductions of levadopa or dopamine agonists (symptoms - anxiety, panic attacks, depression, sweating, nausea, pain, fatigue, dizziness, drug craving) - replace medications at dose prior to onset of symptoms

Question 37

Why should the phenothiazine antiemetics, prochlorperazine and metoclopramide, be avoided in patients with Parkinson’s?

Answer 37

they are dopamine receptor blockers that can aggravate parkinsonian symptoms

Question 38

What is the “wearing off phenomenon”?

Answer 38

increase in motor fluctuations (dyskinesia, abnormal cramps and dystonia) that can occur in patients after 5-10 years of treatment with levadopa or dopamine agonists (likely due to progressive degeneration of nigrostriatal dopamine terminals, which limits uptake and release of dopamine)

Question 39

What is dopaminergic dysregulation syndrome?

Answer 39

compulsive use of dopaminergic drugs - leads to hypomania/mania, impulse control disorders (hypersexuality, pathologic gambling, compulsive buying), and punding (intense fascination with repetitive handling and examination of mechanical objects)

Question 40

What are common motor fluctuations associated with the wearing off phenomenon?

Answer 40

re-emergence of parkinsonian motor problems, unpredictable “off” periods, freezing of gait, failure of “on” response, acute akinesia (sudden exacerbation of Parkinson’s symptoms that lasts for several days and is poorly responsive to treatment), dyskinesia (chorea, dystonia, ballism, myoclonus) - can be exacerbated by protein intake

Question 41

What are approaches to treating the wearing off phenomenon?

Answer 41

reduce protein intake, reduce the intervals between levadopa doses, try alternative formulation of levadopa, add dopamine agonist, add sub-Q apomorphine (dopamine agonist), add COMT inhibitor (entacapone first), add MAO B inhibitor

Question 42

What is chorea?

Answer 42

involuntary movement that jump from one place to anther, being unpredictable in time and place

Question 43

What type of tremor is common in Parkinson’s disease?

Answer 43

involuntary “pill-rolling” movement of the hands, jaw, face and legs - often asymmetrical

Question 44

What is restless leg syndrome?

Answer 44

neurological disorder characterized by throbbing, pulling, creeping, or other unpleasant sensations in the legs and an uncontrollable, and sometimes overwhelming, urge to move them

Question 45

What are Lewy bodies?

Answer 45

abnormal aggregates of protein that develop inside nerve cells in Parkinson’s disease - pathological hallmark of Parkinson’s (identifiable on autopsy)