Neurology: Parkinson's & Benign Essential Tremor Flashcards
Give some causes of Parkinsonism?
1) Parkinson’s disease
2) Drugs e.g. antipsychotics, metoclopramide
3) Progressive supranuclear palsy
4) multiple system atrophy
5) Wilson’s disease
6) post-encephalitis
7) dementia pugilistica (secondary to chronic head trauma e.g. boxing)
8) toxins: carbon monoxide, MPTP
What is Parkinson’s disease (PD)?
A progressive neurodegenerative condition caused by degeneration of dopaminergic neurons in the substantia nigra.
What triad of features is seen in PD?
he reduction in dopaminergic output results in a classical triad of features:
1) Bradykinesia
2) Tremor
3) Rigidity
Are the symptoms of PD characteristically symmetrical or asymmetrical?
Asymmetrical
Mean age of PD diagnosis?
65y
Is PD more common in men or women?
2x more common in men
What is bradykinesia?
How may it typically present?
Slowness of movement:
- Small steps when walking (“shuffling” gait) with reduced arm swinging
- Handwriting gets smaller and smaller (micrographia)
- Difficulty in initiating movement (e.g., going from standing still to walking)
- Rapid frequency of steps to compensate for the small steps and avoid falling (“festinating” gait)
What is the frequency of the tremor in PD?
3-5 Hertz
Describe the tremor seen in PD
- typically ‘pill-rolling’, i.e. in the thumb and index finger
- worse when stressed or tired
- improves with voluntary movement
When is the tremor in PD most marked?
At rest
When does the tremor in PD improve?
With voluntary movement
What makes the tremor in PD get worse?
- Stressed or tired
- When the patient is distracted: e.g. Performing a task with the other hand (e.g., miming the act of painting a fence) exaggerates the tremor.
What is rigidity?
Rigidity is resistance to the passive movement of a joint.
How to test rigidity in PD?
Taking a hand and passively flexing and extending the arm at the elbow demonstrates tension in the arm that gives way to movement in small increments (like little jerks).
What are the 2 types of ridigity that can be seen in PD?
1) Cogwheel rigidity
2) Leadpipe rigidity
Cogwheel vs leadpipe rigidity?
Cogwheel - a combination of lead-pipe rigidity with tremor, jerking resistance to movement
Leadpipe - a constant resistance to motion throughout the entire range of movement.
Other features seen in PD?
1) Reduced facial movements and facial expressions (hypomimia)
2) Depression (affects about 40%)
3) Sleep disturbance and insomnia
4) Anosmia
5) Postural instability (increasing the risk of falls)
6) Cognitive impairment and memory problems
7) Drooling of saliva
Parkinson’s tremor vs benign essential tremor:
a) symmetry
2) frequency
3) better/worse at rest
4) better/worse with intentional movement
5) other Parkinson’s features
6) change with alcohol
PD tremor:
a) asymmetrical
2) 3-5 Hz
3) worse at rest
4) better with intentional movement
5) other Parkinson’s features
6) no change with alcohol
Benign essential tremor:
a) symmetrical
b) 6-12 Hz
3) better at rest
4) worse with intentional movement
5) no other Parkinson’s features
6) improves with alcohol
Describe features of drug-induced parkinsonism vs features of PD
Drug-induced parkinsonism has slightly different features to Parkinson’s disease:
1) motor symptoms are generally rapid onset and bilateral
2) rigidity and rest tremor are uncommon
If there is difficulty differentiating between essential tremor and PD, what investigation can be considered?
I‑FP‑CIT single photon emission computed tomography (SPECT).
What is multiple system atrophy?
A rare condition where the neurones of various systems in the brain degenerate, including the basal ganglia.
Features of multiple system atrophy?
1) Parkinsonism features
2) Autonomic dysfunction: causing postural hypotension, constipation, abnormal sweating and sexual dysfunction
3) Cerebellar dysfunction: causing ataxia
What is dementia with lewy bodies?
A type of dementia associated with features of Parkinsonism.
Associated symptoms in dementia with lewy bodies?
1) Parkinsonism
2) visual hallucinations
3) delusions
4) REM sleep disorders
5) fluctuating consciousness.
4 groups of treatment options in PD?
1) Levodopa (combined with peripheral decarboxylase inhibitors)
2) COMT inhibitors
3) Dopamine agonists
4) Monoamine oxidase-B inhibitors
What is Levodopa?
A synthetic dopamine taken orally.
What is levodopa usually combined with?
a peripheral decarboxylase inhibitor (e.g., carbidopa and benserazide)
Give 2 examples of peripheral decarboxylase inhibitors
1) carbidopa
2) benserazide
Purpose of combining levadopa with a peripheral decarboxylase inhibitor?
stops it from being metabolised in the body before it reaches the brain.
1st line treatment option in PD if the motor symptoms are affecting the patient’s quality of life?
Levodopa
1st line treatment in PD if the motor symptoms are not affecting the patient’s quality of life?
Aopamine agonist (non-ergot derived), levodopa or monoamine oxidase B (MAO‑B) inhibitor
Which class of drug in PD provides the most improvement in motor symptoms?
Levodopa
What are 2 combination drugs given in PD? (i.e. levodopa + peripheral decarboxylase inhibitor)?
1) Co-beneldopa (levodopa and benserazide), with the trade name Madopa
2) Co-careldopa (levodopa and carbidopa), with the trade name Sinemet
What is the main side effect of levodopa?
Dyskinesia (abnormal movements associated with excessive motor activity)
Give 3 examples of dyskinesia that may be seen in levodopa use
1) Dystonia (where excessive muscle contraction leads to abnormal postures or exaggerated movements)
2) Chorea (abnormal involuntary movements that can be jerking and random)
3) Athetosis (involuntary twisting or writhing movements, usually in the fingers, hands or feet)
What may be given to manage dyskinesia associated with levodopa?
Amantadine (a glutamate antagonist)
What are COMT inhibitors?
inhibitors of catechol-o-methyltransferase (COMT).
Give an example of a COMT inhibitor used in PD
entacapone
What is the role of the COMT enzyme?
The COMT enzyme metabolises levodopa in both the body and brain.
Purpose of giving COMT inhibitor (e.g. entacapone) in PD?
Entacapone is taken with levodopa (and a decarboxylase inhibitor) to slow the breakdown of the levodopa in the brain. It extends the effective duration of the levodopa.
Give 3 examples of dopamine agonists used in PD
1) Bromocriptine
2) Pergolide
3) Cabergoline
Levodopa vs dopamine agonists in PD?
Dopamine agonists are less effective than levodopa in reducing symptoms.
When are dopamine agonists typically used in PD?
They are typically used to delay the use of levodopa, then used in combination with levodopa to reduce the required dose.
What is a notable side effect of prolonged use of dopamine agonists?
Pulmonary fibrosis
What are Monoamine oxidase-B inhibitors?
Monoamine oxidase-B inhibitors block the action of monoamine oxidase-B enzymes, helping to increase the circulating dopamine.
Use of monoamine oxidase-B inhibitors in PD?
Monoamine oxidase enzymes break down neurotransmitters such as dopamine, serotonin and adrenaline. Monoamine oxidase-B is more specific to dopamine.
They are typically used to delay the use of levodopa, then in combination with levodopa to reduce the “end of dose” worsening of symptoms.
Give 2 examples of Monoamine oxidase-B inhibitors used in PD?
1) Selegiline
2) Rasagiline
PD medication can be associated with impulse control disorders.
These can occur with any dopaminergic therapy but are more common which which class of drug?
Dopamine agonists
What are 2 risk factors for a patient developing an impulse control disorder on PD medication?
1) a history of previous impulsive behaviours
2) a history of alcohol consumption and/or smoking
Common side effects of levodopa?
dry mouth
anorexia
palpitations
postural hypotension
psychosis
Some adverse effects are due to the difficulty in achieving a steady dose of levodopa.
Give some examples:
1) End-of-dose wearing off: symptoms often worsen towards the end of dosage interval, which results in a decline of motor activity
2) ‘On-off’ phenomenon: large variations in motor performance, with normal function during the ‘on’ period, and weakness and restricted mobility during the ‘off’ period
3) Dyskinesias at peak dose: dystonia, chorea and athetosis (involuntary writhing movements)
What is reason for not acutely stopping levodopa (e.g. if 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
What class of drug is used to treat drug-induced parkinsonism?
Anticholinergics e.g. Procyclidine
What is a benign essential tremor?
It is characterised by a fine tremor affecting all the voluntary muscles.
A relatively common condition associated with older age.
Features of benign essential tremor?
- Tremor most notable in hands
Can affect other areas:
- Head tremor
- Jaw tremor
- Vocal tremor
describe the tremor in benign essential tremor
1) Fine tremor (6-12 Hz)
2) Symmetrical
3) More prominent with voluntary movement
4) Worse when tired, stressed or after caffeine
5) Improved by alcohol
6) Absent during sleep
What are the key differentials of a tremor?
1) PD
2) Benign essential tremor
3) Multiple sclerosis
4) Huntington’s chorea
5) Hyperthyroidism
6) Fever
7) Dopamine antagonists (e.g., antipsychotics)
Management for a benign essential tremor?
There is no definitive treatment for benign essential tremor. The tremor is not harmful and does not require treatment if it is not causing functional or psychological problems.
What are 2 medications that may be used in benign essential tremor?
1) Propranolol (a non-selective beta blocker)
2) Primidone (a barbiturate anti-epileptic medication)
What is the role of monoamine oxidase B?
Monoamine oxidase-B (MAO-B) is an enzyme in the body that breaks down several chemicals in the brain, including dopamine.
