Parkinson's Disease

Question 1

Define what is meant by Parkinsonism [1]

State the three main types [3]

Answer 1

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

Question 2

Describe the basic pathophysiology of PD

Answer 2

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

Question 3

What’s the pathophysiological difference btw IPD and atypical PD? [1]

How do they manifest differently? [1]

Answer 3

IPD:
- Dopamine deficiency
- Later in disease: falling, dementia

Atypical PD:
- minimal to no dopamine deficiency
- early in disease: falling, dementia

Question 4

Name 4 different classes of Parkinson’s Plus Syndromes [4]

State very basic manifestations of each

Answer 4

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.

Question 5

Describe the difference between PD and dementia with DLB [1]

Answer 5

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

Question 6

What triad occurs in secondary parkinsonism due to normal pressure hydrocephalus? [3]

How do you treat? [1]

Answer 6

Triad:
- gait instability
- urinary incont
- cognitive decline

Tx:
- perform a LP and take out fluid
retest above
- put in LP shunt
(efficacy??)

Question 7

Name 4 autonomic symptoms associated with Parkinsonism [4]

Answer 7

Autonomic symptoms:
* Orthostatic hypotension
* Constipation
* Urinary dysfunction
* Erectile dysfunction

Question 8

How can DaT scans help differentiate between idiopathic PD and benign essential tremor? [1]

Answer 8

Essential tremor has normal levels of Da

PD has reduced

Question 9

Describe the clinical motor features of PD [+]

Answer 9

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)

Question 10

Describe the clinical non- motor features of PD [+]

Answer 10

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

Question 11

Why is it important to ask about sleep disturbance in a ptx with ? PD? [1]

Answer 11

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)

Question 12

Describe the three step approach to diagnosing PD [3]

Answer 12

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

Question 13

How do you differentiate between PD and essential tremor? [3]

Answer 13

• 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

Question 14

How do you differentiate between PD and MSA? [3]

Answer 14

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

Question 15

How do you differentiate between PD and PSP? [2]

Answer 15

PSP is characterised by vertical gaze dysfunction, dysarthria and cognitive decline.

Tremor is rare in this condition.

Question 16

How do you differentiate between PD and LBD? [3]

Answer 16

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

Question 17

What is vascular parksinsonism caused by? [1]

How do changes usually occur? [1]

Answer 17

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

Question 18

Describe the drug classes [3] and other management used in the tx of PD (name examples)

Answer 18

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

Question 19

qs about differentials between ps like ones.

Question 20

Dopamine agonists are associated with side-effects and one particular issue is the development of []

Answer 20

Dopamine agonists are themselves associated with side-effects and one particular issue is the development of impulse-control disorders.

Question 21

Describe how you create a management plan for a PD depending on their symptoms [+]

Answer 21

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

Question 22

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

Answer 22

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

Question 23

Deep brain stimulation:

The two primary cortical structures to be targeted are the []

What is the aim of the procedure? [1]

Answer 23

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

Question 24

Which aspects of PD does DBS help [2] but also cause a risk for [3]

Answer 24

The evidence suggests that this procedure improves motor function and movement abnormalities, however poses a risk of strokes, confusion and speech dysfunction

Question 26

Describe the different complications that PD patients are at risk of

Answer 26

Autonomic dysfunction: abnormalities in the control of normal bodily homeostasis
- Postural hypotension
- Constipation
- Urinary dysfunction - increased frequency and urgency

Recurrent falls:

Cognitive impairment

Question 27

Dopamine-receptor agonists can help alleviate symptoms such as [3]

Answer 27

Dopamine-receptor agonists can help alleviate symptoms such as tremors, rigidity and bradykinesia.

Question 28

Ergot-derived dopamine receptor agonists (bromocriptine, cabergoline, pergolide) have been associated with [3]

Answer 28

Ergot-derived dopamine receptor agonists (bromocriptine, cabergoline, pergolide) have been associated with pulmonary, retroperitoneal and cardiac fibrosis.

Question 29

Levodopa usually combined with a decarboxylase inhibitor (e.g. [] or [])

There is usually reduced effectiveness with time (usually by [] years).

Answer 29

Levodopa usually combined with a decarboxylase inhibitor (e.g. carbidopa or benserazide)

There is usually reduced effectiveness with time (usually by 2 years).

Question 30

Describe some of the adverse effects of levodopa therapy [+]

Answer 30

Unwanted effects:
Dyskinesia (involuntary writhing movements)
‘on-off’ effect
Dry mouth
Anorexia
Palpitations
Postural hypotension
Psychosis
Drowsiness

Question 31

Avoid levodopa treatment with [drug type / class] as they contraindicate the effects of levodopa

Answer 31

Do not use with antipsychotics as they contraindicate the effects of levodopa

Question 32

Why should patients avoid eating large amounts of cheese and alcohol if using a MAO-In inhibitor [1]

- Selegiline, Rasagiline

Answer 32

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

Question 33

Name two drugs might use for a PD patient’s LUTS? [2]

Answer 33

Solifenacin, mirabegron

Question 34

If a patient has PD and is suffering from impulse control disorders, which drug class should you remove?

Dopamine agonists
Levodopa
COMTs
MAO-In

Answer 34

If a patient has PD and is suffering from impulse control disorders, which drug class should you remove?

Dopamine agonists
Levodopa
COMTs
MAO-In

Question 35

Why is not continuing PD tx / abruptly stopping PD treatment bad? [1]

Answer 35

Life threatening and potentially fatal Parkinsonism-hyperpyrexia syndrome

Question 36

Give two drugs that are contraindicated in PD [2]

Answer 36

Give two drugs that are contraindicated in PD. Metoclopramide and haloperidol

Question 37

Which of the following causes more risk of hallucinations if given after initial levodopa tx?

Dopamine agonists
Amantadine
MAO-B inhibitors
COMT inhibitors

Answer 37

Which of the following causes more risk of hallucinations if given after initial levodopa tx?

Dopamine agonists
Amantadine
MAO-B inhibitors
COMT inhibitors

Question 38

Consider [] to manage drooling of saliva in people with Parkinson’s disease.

Answer 38

Consider glycopyrronium bromide to manage drooling of saliva in people with Parkinson’s disease.

Question 39

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

Answer 39

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

Question 40

If a patient with PD continues to have postural hypotension which drug can be considered? [1]

Answer 40

If symptoms persist then midodrine (acts on peripheral alpha-adrenergic receptors to increase arterial resistance) can be considered.

Question 41

Vitamin [] supplementation is indicated in Parkinson’s disease.

Vitamin A
Vitamin B
Vitamin C
Vitamin D
Vitamin E

Answer 41

Vitamin [] supplementation is indicated in Parkinson’s disease.

Vitamin A
Vitamin B
Vitamin C
Vitamin D
Vitamin E