Parkinson's Disease Flashcards
Define what is meant by Parkinsonism [1]
State the three main types [3]
Parkinsonism is any condition that causes movement abnormalities. Must have 2 symptoms from list of: Bradykinesia + muscle rigidity ro tremor or postural instability.
* Idiopathic PD
* Atypical Parkinson’s = Parkinson’s Plus Syndromes
* Secondary Parkinsonism
Describe the basic pathophysiology of PD
In Parkinson’s there is a deficiency of dopamine in the nigrostriatal pathway that links the substantia nigra to the basal ganglia, causing the basal ganglia to exert greater inhibitor effects on the thalamus and reduces excitatory input to the motor cortex
What’s the pathophysiological difference btw IPD and atypical PD? [1]
How do they manifest differently? [1]
IPD:
- Dopamine deficiency
- Later in disease: falling, dementia
Atypical PD:
- minimal to no dopamine deficiency
- early in disease: falling, dementia
Name 4 different classes of Parkinson’s Plus Syndromes [4]
State very basic manifestations of each
Progressive Supranuclear Palsy (PSP)
- often fall earlier in disease due to gaze restriction
Multiple Systems Atrophy (MSA) Early and more pronounced autonomic symptoms.
- MSA-P: more akin to PD but might have more autonomic symptoms than idiopathic PD. Often have dry eyes
- MSA-C: gait dysfunction; autonomic dysfunction required for dx
Corticobasal Degeneration (CBD)
- Apraxia, limb dystonia
Lewy Body Dementia (LBD)
- Fluctuating cognition, visual hallucinations, Parkinsonism, and sleep disorders.
Describe the difference between PD dementia and Dementia with Lewy body [1]
Parkinson’s disease dementia:
- dementia occurring in the setting of established Parkinson’s disease. This is defined as having Parkinson’s disease for more than one year before the onset of dementia.
Dementia with Lewy body:
- development of dementia and Parkinsonism concurrently. This is defined as developing dementia within one year of Parkinsonism features
What triad occurs in secondary parkinsonism due to normal pressure hydrocephalus? [3]
How do you treat? [1]
Triad:
- gait instability
- urinary incont
- cognitive decline
The three W’s of normal pressure hydrocephalus (NPH) are:
* Wet: Urinary incontinence
* Wobbly: Gait instability
* Wacky: Cognitive changes
Tx:
- perform a LP and take out fluid
retest above
- put in LP shunt
(efficacy??)
Name 4 autonomic symptoms associated with Parkinsonism [4]
Autonomic symptoms:
* Orthostatic hypotension
* Constipation
* Urinary dysfunction
* Erectile dysfunction
How can DaT scans help differentiate between idiopathic PD and benign essential tremor? [1]
Essential tremor has normal levels of Da
PD has reduced
Describe the clinical motor features of PD [+]
Need a triad of following for a diagnosis:
Resting tremor
- exacerbated by rest / improves when engages in purposeful actions
- ‘pill-rolling’
- begins as an intermittent tremor, and as the disease progresses the tremor becomes more continuous
- starts unilateral can progress to bilateral
Muscle rigidity
- ‘cogwheel rigidity’
- muscular stiffness, stooped posture, and reduced arm swing when walking
Bradykinesia
- reduction in manual dexterity of finger movements
- difficulty standing from a seated position
- troubles when walking
Other characteristics:
- Postural instability
- Mask-like facies (hypomimia)
- Micrographia
- Dysphagia (due to bradykinesia of pharyngeal muscles)
Describe the clinical non- motor features of PD [+]
Mood disturbance
* Depression (50%)
* Apathy ( 40%)
* Anxiety (30%)
Psychiatric symptoms
* Psychotic episodes (may be due to dopaminergic medications, underlying Lewy-body dementia, or both)
* Visual hallucinations
* Paranoid delusions (typically patients have good insight)
Sleep dysfunction
* Frequently restless legs syndrome, insomnia and daytime somnolence
* Frequent awakening through the night and early morning waking are common, independent from depression
Why is it important to ask about sleep disturbance in a ptx with ? PD? [1]
When taking a Hx, important to ask if they have vivid dreams / fight or shout in their dreams - as could indicate they have a REM sleep behaviourr disorder (close indication between this & PD)
Describe the three step approach to diagnosing PD [3]
Step 1: triad of muscular rigidity; resting tremor (4-6 Hz frequency); postural instability
Step 2. :Exclusion of various criteria
Step 3: 3+ supportive criteria (in addition to step 1)
* Unilateral onset
* Resting tremor
* Progressive disease
* Persistent asymmetry, affecting initial side of onset most
* Excellent response (70-100%) to levodopa treatment
* Severe levodopa-induced chorea
* Levodopa response for greater than 5 years
* Clinical course of greater than 10 years
How do you differentiate between PD and essential tremor? [3]
- An essential tremor worsens when holding the arms outstretched
- An essential tremor worsens with activities such as writing, whereas the tremor associated with Parkinson’s disease improves with purposeful actions
- Most often is symmetrical, however can sometimes be asymmetric
How do you differentiate between PD and MSA? [3]
In multiple system atrophy, there is usually a degree of cerebellar involvement (MSA-C), which is part of the exclusion criteria for Parkinson’s disease
Profound autonomic dysfunction leading to severe postural hypotension, urogenital dysfunction and a plethora of other features including cerebellar and corticospinal features.
Poor response to treatment
How do you differentiate between PD and PSP? [2]
PSP is characterised by vertical gaze dysfunction, dysarthria and cognitive decline.
Tremor is rare in this condition.
How do you differentiate between PD and LBD? [3]
Lewy-body dementia, the dementia usually occurs concomitantly with, or prior to, the development of parkinsonism
DLB is characterised by early onset dementia (< 1 year)
Characterised by a triad of visual hallucinations, fluctuating cognition, and parkinsonism
What is vascular parksinsonism caused by? [1]
How do changes usually occur? [1]
Vascular parkinsonism:
* Due to multiple infarcts affecting the basal ganglia
* Usually can be identified via a thorough history and radiological findings
* Probably step-wise progression rather than continuous
Describe the drug classes [3] and other management used in the tx of PD (name examples)
When first suspected by any medical professional, the NICE guidelines recommend that a person should be referred quickly and untreated to a specialist with Parkinson’s disease expertise first for assessment.
Levodopa (converted into dopamine for use within the brain by DOPA decarboxylase once it crosses the blood brain barrier) AND a DOPA decarboxylase inhibitor (DDCI) (to avoid peripheral conversion prior to passing BBB)
Monoamine oxidase B (MAO-B) inhibitors
- Inhibitors of MAO-B, which are responsible for degrading dopamine, therefore increasing the amount of dopamine available
- rasagiline and selegiline
COMT inhibitors
- Entacapone
- Inhibit the peripheral breakdown of levodopa by the COMT enzyme allowing more levodopa to cross the blood brain barrier
Anti-muscarinics
- e.g. procyclidine may be used although evidence is poor.
- Amantadine may be used as early monotherapy or late adjuvant to help with dyskinesia.
Non-selective dopamine agonists:
- Apomorphine
- generally reserved for advanced disease.
- It is given via subcutaneous injection/infusion, but can cause significant postural hypotension.
Dopamine agonists
- Mimic dopamine and bind to dopamine receptors to exert their effect
- Non-ergot (e.g. ropinirole, pramipexole)
- Ergot-derived dopamine agonists (e.g. bromocriptine, cabergoline)
Deep brain stimulation:
- For people whose symptoms are not adequately controlled by medical therapy
- This should never be used as first-line treatment
Adjuvant therapy:
- Physiotherapy (reduce falls)
- Speech therapy
- OT
qs about differentials between ps like ones.
Dopamine agonists are associated with side-effects and one particular issue is the development of []
Dopamine agonists are themselves associated with side-effects and one particular issue is the development of impulse-control disorders.
Describe how you create a management plan for a PD depending on their symptoms [+]
First-line treatment for early stage disease depends on the impact of the motor symptoms on the patient’s quality of life
- If motor symptoms IMPACT on quality of life - levodopa
- If motor DO NOT IMPACT - dopamine agonist, levodopa or MAO-B inhibitors
Whether it is a DA; MOABIn or levodopa - should be determined by:
- The patient’s current symptom profile
- Patient age
- Current co-morbidities and existing medications
- RIsks of meds
Deep brain stimulation:
- For people whose symptoms are not adequately controlled by medical therapy
PD
According to the NICE guidelines, [drug class] should not be used first line, only if required as an adjunct or alternative after failure of initial therapy
According to the NICE guidelines, ergot-derived dopamine agonists (e.g bromocriptine, cabergoline) should not be used first line, only if required as an adjunct or alternative after failure of initial therapy
Deep brain stimulation:
The two primary cortical structures to be targeted are the []
What is the aim of the procedure? [1]
The two primary cortical structures to be targeted are the globus pallidus interna and the subthalamic nucleus
This procedure aims to correct the imbalance created by reduced function of the substantia nigra, to improve the symptoms for patients
Which aspects of PD does DBS help [2] but also cause a risk for [3]
The evidence suggests that this procedure improves motor function and movement abnormalities, however poses a risk of strokes, confusion and speech dysfunction
Describe the different complications that PD patients are at risk of
Autonomic dysfunction: abnormalities in the control of normal bodily homeostasis
- Postural hypotension
- Constipation
- Urinary dysfunction - increased frequency and urgency
Recurrent falls:
Cognitive impairment
Dopamine-receptor agonists can help alleviate symptoms such as [3]
Dopamine-receptor agonists can help alleviate symptoms such as tremors, rigidity and bradykinesia.
Ergot-derived dopamine receptor agonists (bromocriptine, cabergoline, pergolide) have been associated with [3]
Ergot-derived dopamine receptor agonists (bromocriptine, cabergoline, pergolide) have been associated with pulmonary, retroperitoneal and cardiac fibrosis.
Levodopa usually combined with a decarboxylase inhibitor (e.g. [] or [])
There is usually reduced effectiveness with time (usually by [] years).
Levodopa usually combined with a decarboxylase inhibitor (e.g. carbidopa or benserazide)
There is usually reduced effectiveness with time (usually by 2 years).
Describe some of the adverse effects of levodopa therapy [+]
Unwanted effects:
Dyskinesia (involuntary writhing movements)
‘on-off’ effect
Dry mouth
Anorexia
Palpitations
Postural hypotension
Psychosis
Drowsiness
Avoid levodopa treatment with [drug type / class] as they contraindicate the effects of levodopa
Do not use with antipsychotics as they contraindicate the effects of levodopa
Why should patients avoid eating large amounts of cheese and alcohol if using a MAO-In inhibitor [1]
- Selegiline, Rasagiline
Hypertensive crisis may occur if large amounts of tyramine (an amine broken down by MAO) are consume so patient must cut down on aged cheeses and alcohol
Name two drugs might use for a PD patient’s LUTS? [2]
Solifenacin, mirabegron
If a patient has PD and is suffering from impulse control disorders, which drug class should you remove?
Dopamine agonists
Levodopa
COMTs
MAO-In
If a patient has PD and is suffering from impulse control disorders, which drug class should you remove?
Dopamine agonists
Levodopa
COMTs
MAO-In
Why is not continuing PD tx / abruptly stopping PD treatment bad? [1]
Life threatening and potentially fatal Parkinsonism-hyperpyrexia syndrome
Give two drugs that are contraindicated in PD [2]
Give two drugs that are contraindicated in PD. Metoclopramide and haloperidol
Which of the following causes more risk of hallucinations if given after initial levodopa tx?
Dopamine agonists
Amantadine
MAO-B inhibitors
COMT inhibitors
Which of the following causes more risk of hallucinations if given after initial levodopa tx?
Dopamine agonists
Amantadine
MAO-B inhibitors
COMT inhibitors
Consider [] to manage drooling of saliva in people with Parkinson’s disease.
Consider glycopyrronium bromide to manage drooling of saliva in people with Parkinson’s disease.
Impulse control disorders have become a significant issue in recent years. These can occur with any dopaminergic therapy but are more common with:
Dopamine agonists
Amantadine
MAO-B inhibitors
COMT inhibitors
Impulse control disorders have become a significant issue in recent years. These can occur with any dopaminergic therapy but are more common with:
Dopamine agonists
Amantadine
MAO-B inhibitors
COMT inhibitors
If a patient with PD continues to have postural hypotension which drug can be considered? [1]
If symptoms persist then midodrine (acts on peripheral alpha-adrenergic receptors to increase arterial resistance) can be considered.
Vitamin [] supplementation is indicated in Parkinson’s disease.
Vitamin A
Vitamin B
Vitamin C
Vitamin D
Vitamin E
Vitamin [] supplementation is indicated in Parkinson’s disease.
Vitamin A
Vitamin B
Vitamin C
Vitamin D
Vitamin E
Pyschosis
palpitations
Hypotension
Hypotension
Bromocriptine may cause pulmonary, retroperitoneal and cardiac fibrosis
Antipsychotics may cause parkinsonism
metoclopramide
Parkinsonism, autonomic disturbance, cerebellar signs - multiple system atrophy
MSA
PSP
