Flashcards in Parkinson's Disease Deck (45):
What are the 4 cardinal signs of Parkinson's?
(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)
What is the pathophysiology of Parkinson's?
destruction of dopaminergic neurons in the brain stem (particularly the substantia nigra) leading to development of dopamine deficiency and the development of Lewy Bodies
What is the primary defect in Parkinson's?
loss of dopamine in the corpus stratium (the caudate and lentiform nuclei)
What is the pathological hallmark of Parkinson's?
Lewy bodies - abnormal aggregates of protein (alpha-synuclein) that develop inside nerve cells - definitive diagnosis but only seen on autopsy
What is the substantia nigra?
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
When do symptoms of Parkinson's appear?
when 70-80% of dopaminergic neurons have died
What is Parkinsonism?
any of a group of nervous system disorders with symptoms similar to Parkinson's Disease
How is clinically established Parkinson's diagnosed?
presence of parkinsonism, no absolute exclusion criteria, at least 2 supportive criteria, and no red flags
What are supportive factors for a diagnosis of Parkinson's?
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
What is bradykinesia?
generalized slowness of movement, starts distally (in arms with decrease in manual dexterity of fingers), progresses to dragging of legs/shuffling gait
How does tremor present in Parkinson's?
unilateral resting tremor (not engaged in purposeful activities) - can be intermittent
How does rigidity present in Parkinson's?
increased resistance to passive movement, often begins unilaterally
What is cogwheel rigidity?
ratchet pattern of resistance and relaxation
What is leadpipe rigidity?
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
What is the common hand motion associated with Parkinson's?
pill rolling of hand
What is the "pull test"?
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
What are the craniofacial motor features of Parkinson's?
hypomimia (masked facial expression), decreased spontaneous eye blink, sialorrhea (excessive salivation)
What are some red flags that could suggest a diagnosis other than Parkinson's?
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
What is a positive dopaminergic challenge test?
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
What is the first-line treatment for Parkinson's?
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)
What are some additional pharmacological treatments for Parkinson's?
dopamine agonists, monoamine oxidase (MAO) B inhibitors, antichlinergic agents, amantadine, catechol-O-methyl transferase (COMT) inhibitors
What are some side effects of levodopa?
nausea (take with food early in treatment), somnolence, dizziness, headache, confusion, hallucinations, delusions, agitation, psychosis, orthostatic hypotension
What is carbidopa?
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
What is the mechanism of action of dopamine agonists (bromocriptine/Parlodel, pramipexole/Mirapex, ropinirole/Requip) in Parkinson's?
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
What is the mechanism of action of MAO B inhibitors (selegiline - 5 mg daily, rasagiline - 1 mg daily) in Parkinson's?
delays destruction of neurons and inhibits metabolic breakdown of dopamine (AE: nausea, headache, insomnia, confusion, enhanced levodopa AEs)
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?
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)
What is the mechanism of action of amantadine (Symmetrel/Symadine - 200-300 mg/day) in Parkinson's?
unknown - antiviral medication - useful for akinesia and rigidity (AE: livedo reticularis [mottled skin], ankle edema)
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?
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
What is deep brain stimulation?
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
What is Parkinson disease?
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
What is the "gold standard" for diagnosis of Parkinson's disease?
neuropathological examination (can only be done on autopsy)
What are red flags in the diagnosis of Parkinson's disease?
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
What are the criteria for clinically established Parkinson's?
presence of parkinsonism, no absolute exclusion criteria, at least two supportive criteria
What are supportive criteria of the diagnosis of Parkinson's?
clear response to dopaminergic therapy, presence of levodopa-induced dyskinesia, rest tremor of a limb, presence of olfactory loss or cardiac sympathetic denervation
What are the criteria for clinically probable Parkinson's?
presence of parkinsonism, no absolute exclusion criteria, presence of red flags is counterbalanced by supportive criteria (no more than 2 red flags allowed)
What is parkinsonism-hyperpyrexia syndrome?
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
Why should the phenothiazine antiemetics, prochlorperazine and metoclopramide, be avoided in patients with Parkinson's?
they are dopamine receptor blockers that can aggravate parkinsonian symptoms
What is the "wearing off phenomenon"?
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)
What is dopaminergic dysregulation syndrome?
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)
What are common motor fluctuations associated with the wearing off phenomenon?
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
What are approaches to treating the wearing off phenomenon?
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
What is chorea?
involuntary movement that jump from one place to anther, being unpredictable in time and place
What type of tremor is common in Parkinson's disease?
involuntary "pill-rolling" movement of the hands, jaw, face and legs - often asymmetrical
What is restless leg syndrome?
neurological disorder characterized by throbbing, pulling, creeping, or other unpleasant sensations in the legs and an uncontrollable, and sometimes overwhelming, urge to move them