Parkinson's

Question 1

Characteristics of Parkinson’s syndrome

Answer 1

-Bradykinesia (poverty of movement/ hypokinesia, short shuffling steps with reduced arm swinging, difficulty initiating movement)
-Rigidity (lead pipe, cogwheel due to superimposed tremor)
-Tremor (most marked at rest, 3-5 Hz, worse when stressed or tired, improves with voluntary movement, pin-rolling)
-Postural instability

Question 2

Other characteristics features of Parkinson’s

Answer 2

Other characteristic features
mask-like facies
flexed posture
micrographia
drooling of saliva
psychiatric features: depression is the most common feature (affects about 40%); dementia, psychosis and sleep disturbances may also occur
impaired olfaction
REM sleep behaviour disorder
fatigue
autonomic dysfunction:
postural hypotension

Question 3

Underlying structure targeted in Parkinsonism

Answer 3

-Extrapyramidal
=basal ganglia
=certain brain stem nuclei
=Connections

Question 4

What does the Extrapyramidal system do?

Answer 4

-Modifying and organising movements
=Encouraging wanted movements
=Inhibiting unwanted movements
=Organising individual movements into actions

-Sequenced learned voluntary acts
-Semi-automatic movements
-Emotional movements

Question 5

Describe bradykinesia

Answer 5

-Primary cause of motor disability
-Slowness and difficulty in performing actions
=Initiating, stopping, executing
-Actions formed of sequenced patterns
=walking, writing
-Individual movements= power unaffected

Question 6

Where is bradykinesia especially seen in?

Answer 6

-Learned, sequenced actions that are done automatically (walking)
-Automatic things like blinking, swallowing saliva, fidgeting
-Emotional/ communicative actions (non-verbal gestures, facial expressions)

Question 7

Describe rigidity in Parkinson’s

Answer 7

-Increased in tone
-Different in spasticity in UMN pyramidal disease

Question 8

Describe tremor in Parkinson’s

Answer 8

-Not necessary for Parkinsonism
-Most obvious feature
=Present at rest
=3-5 Hz
=Worse when stressed or tired
=Improves with voluntary movement
=Pill-rolling

Question 9

Actual causes of Parkinson’s

Answer 9

-Drug-induced
-Idiopathic disease
-Other primary degenerative diseases
-Miscellaneous

Causes of Parkinsonism
Parkinson’s disease
drug-induced e.g. antipsychotics, metoclopramide*
progressive supranuclear palsy
multiple system atrophy
Wilson’s disease
post-encephalitis
dementia pugilistica (secondary to chronic head trauma e.g. boxing)
toxins: carbon monoxide, MPTP

Question 10

Drug causes of Parkinson’s

Answer 10

-Chlorpromazine (anti-psychotic) in young
-Prochlorperazine (anti-nausea) in old

motor symptoms are generally rapid onset and bilateral
rigidity and rest tremor are uncommon

Question 11

Describe idiopathic Parkinson’s disease

Answer 11

-Lewy bodies
-Substantia nigra neuronal death
-Related loss of neuromelanin
-Deposition of abnormal folded protein- alpha-synuclein
-Nigro-striatal dopaminergic deficit

-Neurogenerative disease

Parkinson’s disease is a progressive neurodegenerative condition caused by degeneration of dopaminergic neurons in the substantia nigra. The reduction in dopaminergic output results in a classical triad of features: bradykinesia, tremor and rigidity. The symptoms of Parkinson’s disease are characteristically asymmetrical.

Question 12

Clinical signs of idiopathic Parkinson’s disease for diagnosis

Answer 12

-Insidious onset, Men twice as common, 65+
-Gradually progressive
-Parkinsonian features
=Postural instability not an early feature
-Typically unilateral onset
-No other features (pure= cerebellar ataxia, pyramidal weakness)

Question 13

Investigations for IPD

Answer 13

-Arguably none in typical cases
-CT/MR imaging not routinely necessary = SPECT
-DAT-Scan may be helpful when uncertain
-Dopaminergic agent trial

Question 14

Types of treatment for Parkinson’s

Answer 14

-Prophylactic
-Symptomatic
-Disease-modifying

Question 15

IPD treatment (symptomatic)

Answer 15

-Levodopa (motor symptoms)
-Dopamine agonist
-Monoamine oxidase B
-COMT inhibitor

-DDA (Direct Dopamine Agonists)= Ropinorole
-LDOPA (Madopar, Sinemet) (dopamine precursor)
-Selegeline (monoamine oxidase inhibitor)
-Amantadine
-Anticholinergic drugs

For first-line treatment:
if the motor symptoms are affecting the patient’s quality of life: levodopa
if the motor symptoms are not affecting the patient’s quality of life: dopamine agonist (non-ergot derived), levodopa or monoamine oxidase B (MAO-B) inhibitor

If a patient continues to have symptoms despite optimal levodopa treatment or has developed dyskinesia then NICE recommend the addition of a dopamine agonist, MAO-B inhibitor or catechol-O-methyl transferase (COMT) inhibitor as an adjunct.

NICE reminds us of the risk of acute akinesia or neuroleptic malignant syndrome if medication is not taken/absorbed (for example due to gastroenteritis) and advise against giving patients a ‘drug holiday’ for the same reason.

Impulse control disorders have become a significant issue in recent years. These can occur with any dopaminergic therapy but are more common with:
dopamine agonist therapy
a history of previous impulsive behaviours
a history of alcohol consumption and/or smoking

If excessive daytime sleepiness develops then patients should not drive. Medication should be adjusted to control symptoms. Modafinil can be considered if alternative strategies fail.

If orthostatic hypotension develops then a medication review looking at potential causes should be done. If symptoms persist then midodrine (acts on peripheral alpha-adrenergic receptors to increase arterial resistance) can be considered.

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

Question 16

Why are there emerging problems in IPD treatment longer term?

Answer 16

-Progressive disease (treatment is symptomatic)
-Drug toxicity
-CNS plasticity- changes in neuronal transmission
=Reduced efficacy
=Shorter durations of response
=Fluctuations in disability
=Unpredictable and variable response- emergence of involuntary movements (chorea, Athetosis, dystonia/ confusion, hallucinations, dementia)

Question 17

Signs of Parkinson’s disease

Answer 17

-Reduced arm swing
-Difficulty with balance and coordination
-No loss of power or sensation
-Postural instability
-Short shuffling steps
-Difficulty initiating movement
-Lead pipe rigidity and cogwheel (superimposed tremor)
-Flexed posture

Question 18

Overview of Levodopa

Answer 18

-More improvement in motor symptoms
-More improvement in activities of daily living
-More motor complications
-Fewer specific adverse effects: excessive sleepiness, hallucinations, impulse control disorders

nearly always combined with a decarboxylase inhibitor (e.g. carbidopa or benserazide)
this prevents the peripheral metabolism of levodopa to dopamine outside of the brain and hence can reduce side effects
common adverse effects:
dry mouth
anorexia
palpitations
postural hypotension
psychosis
some adverse effects are due to the difficulty in achieving a steady dose of levodopa
end-of-dose wearing off: symptoms often worsen towards the end of dosage interval. This results in a decline of motor activity
‘on-off’ phenomenon: large variations in motor performance, with normal function during the ‘on’ period, and weakness and restricted mobility during the ‘off’ period
dyskinesias at peak dose: dystonia, chorea and athetosis (involuntary writhing movements)
these effects may worsen over time with - clinicians therefore may limit doses until necessary
it is important not to acutely stop levodopa, for example, if a patient is admitted to hospital
if a patient with Parkinson’s disease cannot take levodopa orally, they can be given a dopamine agonist patch as rescue medication to prevent acute dystonia

Question 19

Overview of dopamine agonists

Answer 19

-Less improvement in motor symptoms
-Less improvement in activities of daily living
-Fewer motor complications
-More specified adverse events

e.g. bromocriptine, ropinirole, cabergoline, apomorphine
ergot-derived dopamine receptor agonists (bromocriptine, cabergoline) have been associated with pulmonary, retroperitoneal and cardiac fibrosis. The Committee on Safety of Medicines advice that an echocardiogram, ESR, creatinine and chest x-ray should be obtained prior to treatment and patients should be closely monitored
patients should be warned about the potential for dopamine receptor agonists to cause impulse control disorders and excessive daytime somnolence
more likely than levodopa to cause hallucinations in older patients. Nasal congestion and postural hypotension are also seen in some patients

Question 20

Overview of MAO-B inhibitors

Answer 20

-Less improvement in motor symptoms and activities of daily living
-Fewer motor complications
-Fewer adverse events

e.g. selegiline
inhibits the breakdown of dopamine secreted by the dopaminergic neurons

Question 21

Overview of Amantadine

Answer 21

-No evidence of improvement in motor/ activities
-mechanism is not fully understood, probably increases dopamine release and inhibits its uptake at dopaminergic synapses
side-effects include ataxia, slurred speech, confusion, dizziness and livedo reticularis

Question 22

Overview of COMT inhibitors

Answer 22

-Improvement in motor and activties, off time reduction, more adverse reactions, lower hallucination risk

-(Catechol-O-Methyl Transferase) inhibitors
e.g. entacapone, tolcapone
COMT is an enzyme involved in the breakdown of dopamine, and hence may be used as an adjunct to levodopa therapy
used in conjunction with levodopa in patients with established PD

Question 23

Overview of Antimuscarinics

Answer 23

-block cholinergic receptors
now used more to treat drug-induced parkinsonism rather than idiopathic Parkinson’s disease
help tremor and rigidity
e.g. procyclidine, benzotropine, trihexyphenidyl (benzhexol)