Parkinson's Disease Flashcards
Helpful historical features for diagnosing Parkinson’s
- Presence of parasomnias/REM sleep behavior disorders
- Micrographia
- Mask fascies / flat affect
- Shuffling gait and difficulty turning
- Hyposmia (80 - 100% of patients over the course of the disease)
Families of drugs used to treat Parkinson’s
- Dopaminergic agonists (levodopa/carbidopa)
- MAO type B inhibitors
- Catechol-O-methyltransferase (COMT) inhibitors
Main four Parkinson’s Plus syndromes
- Dementia with Lewy Bodies
- Multiple systems atrophy
- Corticobasal degeneration
- Progressive supranuclear palsy
Parkinsonism
Clinical triad of bradykinesia, rigidity, and resting tremor
Sometimes also includes postural instability, which develops later in the disease progression.
Gets its name from Parkinson’s disease, but appears in many clinical scenarios. The most common cause is idiopathic Parkinson’s disease
Causes of secondary parkinsonism
- Drug exposure
- Stroke
- Parkinson’s Plus syndrome
Lewy bodies
Inclusion bodies of alpha synuclein that develop in neurons in both Parkinson’s Disease and Lewy Body dementia
Appear as an eosinophilic cytoplasmic inclusion consisting of a dense core surrounded by a halo of 10-nm-wide radiating fibrils
Vascular parkinsonism
Results from subcortical infarcts affecting the extrapyramidal motor system
Should be considered in a patient with a history of stroke, CAD, or PAD who presents with new onset parkinsonism
More commonly associated with “negative” Parkinsonian symptoms (bradykinesia, rigidity). Tremor is often absent.
Drug-induced parkinsonism
Caused by dopamine blocking agents: antipsychotics, antiemetics (specifically metoclopramide)
Multiple Systems Atrophy
- Associated with parkinsonism or cerebellar features with prominent autonomic insufficiency
- Orthostatic hypotension, constipation, urinary frequency, impotence
- Two forms:
- MSA-P: MSA with parkinsonism
- MSA-C: MSA with cerebellar dysfunction
Diffuse Lewy Body disease (aka Lewy Body Dementia)
- Dementia syndrome frequently associated with Parkinsonism
- Key features:
- Parkinsonism
- Clinical fluctuation
- Visual hallucinations
- Marked sensitivity to neuroleptics
- Pathology:
- Diffuse Lewy bodies
- Loss of cholinergic neurons
- Treatment:
- Cholinesterase inhibitors (stigmines)
- Quetiapine and clozapine (the atypical antipsychotics) are preferred as they are less likely to worsen parkinsonian symptoms
- Parkinsonian symptoms generally less responsive to carbidopa/levodopa than primary PD
Corticobasal degeneration
- Neurodegenerative disorder with Parkinsonism and prominent ataxia
-
Alien limb phenomenon is often observed and is considered a hallmark finding
- Feeling that the limb has a mind of its own and is controlling its own movements
- Predominantly unilateral, much like primary Parkinson’s Disease
Progressive supranuclear palsy
- Neurodegenerative condition which presents with parkinsonism and impaired voluntary vertical gaze
-
Impaired downward gaze is the most specific historical finding
- Often presents as gaze limitations leading to frequent falls
- Doll’s eyes testing remains intact (unlike vistibular lesions), as brainstem pathways are unaffected
How much of PD is familial vs sporadic?
10% familial
90% sporadic
Levodopa
Crosses the blood-brain barrier (unlike dopamine) and is converted to dopamine on the other side.
Peripheral breakdown in the gut is inhibited by adding carbidopa to block the activity of aromatic amino acid decarboxylase. Levodopa is also broken down by the enzyme COMT, so COMT inhibitors (entacapone, tolcapone) are also useful adjunct therapies.
Treatment paradigms generally favor levodopa sparing therapies initially unless symptoms are severe at the time of diagnosis (as levodopa will inevitably lead to levodopa-induced dyskinesia over time). Over time, response to levodopa may become fluctuant.
COMT inhibitors
Entacapone, tolcapone
Dopamine agonists for PD
Cross the blood brain barrier and act predominantly at D2 receptors without requiring conversion.
Include pramipexole, ropinirole, and rotigotine.
More likely to cause problems with impulsivity, including dopamine-induced gambling syndrome, excessive shopping, and hypersexual tendencies.
MAO-B inhibitors for PD
Selegiline, rasagiline
Improve symptoms in patients with mild disease as a monotherapy, and can also be used as an adjunct to levodopa.
Many clinicians prefer MAO-B inbitiors for patients younger than 75 and/or with mild PD.
These drugs should be used cautiously with other drugs that may induce serotonin syndrome.
Amantadine for PD
Acts by blocking glutamate NMDA receptors
Has mild attenuation of the cardinal parkinsonian symptoms of resting tremor and dystonia.
Similar to MAO-B inbitiors, amantadine may be used for early and/or mild PD.
Also shown to help alleviate levodopa-induced dyskinesias.
Deep brain stimulation for PD
For cases refractory to medical therapy
Dementia is an exclusion criterion, as worsening of dementia has been reported following DBS.
Involves placement of stimulating electrodes into the subthalamic nucleus or globus pallidus interna bilaterally.
Dopaminergic antagonist antiemetics
Prochlorperazine (aka compazine)
and metoclopramide (aka reglan)
Dopaminergic depleting medications
Reserpine, tetrabenazine
Both are centrally acting vesicular monoamine transporter blockers which reduce outflow of all monoamines (dopamine, serotonin, norepinephrine, and histamine)
Reserpine is usually used as an antihypertensive, while tetrabenazine is used to treat choreiform movement disorders like Huntington’s. Both may cause drug-induced parkinsonism, similar to antipsychotics and dopamine-blocking antiemetics.
Best “test” for true Parkinson’s disease
Therapeutic trial of levodopa
If they don’t respond well, it is more likely to be something else (or maybe a Parkinson’s Plus syndrome like LBD)
Hot-Cross Bun sign in the brainstem on MRI
Present in multiple systems atrophy
Two components of “bradykinesia”
- Slower movements
- Lower amplitude movements
Anticholinergics in Parkinson’s disease
- Can be used in younger patients who (1) will have relatively unaffected cognition and (2) will likely need levodopa later in life, but will live for more than ~15 years and experience its side effects
- Some of the anticholinergis used for this purpose are:
- Trihexyphenidyl
- Benztropine
- Biperiden
Main side effect of amantadine
~5% of patients may develop livedo reticularis and peripheral edema
Parkinson’s drugs and where they work
