parkinsons

Question 1

73 y.o. man admitted for routine hernia repair.

wife says his voice has changed, words becoming hard to understand, mumbles

you suspect he has dysarthria

(a) O/E, speech normal but words poorly articulated. expressionless face, reduced blink rate, tendency to drool.

likely dx?

Answer 1

idiopathic Parkinson’s disease

Question 2

(b) what other features would you look for on examination? suggest 4

Answer 2

1. rigidity (leadpipe / cogwheel)
2. bradykinesia + loss of arm swing
3. pill-rolling resting tremor
4. festinant gait

Question 3

(c) what pathophysiological change underlies this disease?

Answer 3

degeneration of dopaminergic neurones in the substantia nigra

reduced inhibitory dopaminergic activity of the nigrostriatal pathway

Question 4

(e) the usual rx for this condition is a combination of 2 drugs given as a single preparation. what are these and why is the combination necessary.

Answer 4

1. Levodopa
2. Peripheral dopa decarboxylase inhibitor (Carbidopa)

(Sinemet is combination)

Peripheral dopa decarboxylase inhibitor helps prevent the metabolism of L-dopa before reaching dopaminergic neurones, therefore reducing side-effects.

Question 5

(e) name two classes of drugs (with one example of each) that can cause these sx

Answer 5

1. antipsychotics (typical) - haloperidol
2. antiemetics (dopamine antagonist) - metoclopramide

Question 6

64 y.o. man attends GP complaining of tiredness and “shakiness”

finds it difficult to get started walking, feels unsteady on his feet, generally slower at activities

wife states shakiness in his hands has gradually worsened and he gets frustrated trying to fasten buttons

noticed that his writing has become very small and barely legible

GP suspects idiopathic PD

(a) clinical features of PD comprise a classical triad. what are they? suggest a feature of each you would expect to see on examination.

Answer 6

1. tremor
   
   • present at rest / occur in the hands, legs, tongue, lips, eyes
   • not present upon movement / disappears during sleep / pill-rolling movement
2. rigidity
   
   • felt throughout the ROM / present in limbs, trunk and neck / often asymmetrical / lead-pipe / cog-wheel
3. bradykinesia
   
   • expressionless face / quiet / monotonous voice / poor fine motor tasking / turning using the trunk / slow, shuffling gait

Question 7

(b) what sensory signs would you expect to see in PD?

Answer 7

none

Question 8

(c) explain how the pathological process occuring in the brain results in the clinical features

Answer 8

• degeneration of melanin containing dopaminergic neurones of the substantia nigra
• reduced inhibitory dopaminergic activity of the nigrostriatal pathway
• cholinergic hyperactivity from corpus striatus
• parkinsonian syndrome ensues
• loss of approximately 70% of neurones required before sx appear

Question 9

(d) PD can be classified as an akinetic-rigid syndrome.
* *list 3 other examples of akinetic rigid syndrome.**

Answer 9

1. drug-induced parkinsonism
2. MPTP-induced parkinsonism
3. post-encephalitic parkinsonism
4. Parkinsonism plus
5. childhood akinetic-rigid syndrome

Question 10

(e) what is the difference between parkinsonism and idiopathic parkinson’s disease?

Answer 10

parkinsonism denotes a syndrome that appears clinically similar to idiopathic parkinson’s disease but has a different pathological or aetiological basis

Question 11

(f) name 2 classes of drugs used in the rx of PD that act centrally. describe their MOA.

Answer 11

1. dopamine precursor
   
   • ^{e.g. L-dopa}
   • ^{an immediate precursor of dopamine, able to penetrate BBB where it is then decarboxylated to dopamine and thus, replenishes domanine content of corpus striatum}
2. monoamine oxidase B inhibitors
   
   • ^{inhibit dopamine degradation in CNS}
3. dopamine agonists
   
   • ^{mimics effects of dopamine by acting on D2 receptors}
4. dopamine releases
   
   • ^{facilitate neuronal dopamine release and inhibit its reuptake into nerves}
5. anticholinergic drugs
   
   • ^{act antagonistically at muscarinic receptors that mediate strial cholinergic excitation}

Question 12

(g) draw a synapse and mark on the figure where the 2 drugs act

Question 13

(h) what issues need to be considered when using drug therapy for the rx of PD? suggest 2

Answer 13

1. side effects of medication
2. cost of medication - on multiple drugs for many years
3. time course of drug administration due to ‘wearing off’ effect

Question 14

(i) what psychiatric illness is common folowing dx in pts suffering from PD and what may you use to treat this?

Answer 14

depression treated with an SSRI / MAOI / tricyclics

Question 15

A 78-year old man with known Parkinson’s disease presents to his GP as he feels hat his symptoms are worsening. He complains that one minute his arms completely “lock off” and he can’t move them at all, then the next they are
“shaking like a leaf”.

dx?

Answer 15

“on-off” effect

Question 16

A 52-year old woman presents with a 6 month history of falls associated with dizziness. On examination she has marked postural hypotension and is ataxic.

dx?

Answer 16

multisystem atrophy / Shy-Drager syndrome

Question 17

A previously fit and well 71-year old man presents to the GP with a productive cough. However, while he is there the GP notices he has a stooped posture, takes small, shuffling steps when he walks and has poor ‘swing through’ of the right upper limb. He also notes cogwheel rigidity of the right upper limb.

dx?

Answer 17

idiopathic PD

Question 18

A 48-year old man presents to his GP with what he describes as an increased frequency of ‘tics’. He has uncontrollable, brief, jerky, movements that flit from one part of the body to another.

dx?

Answer 18

Huntington’s chorea

Question 19

A 19-year old man is referred to neurology outpatients with ‘features of Parkinson’s disease’. His liver function tests are deranged and he has reduced copper and caeruloplasmin levels.

dx?

Answer 19

Wilson’s disease

Question 20

A 68- year- old man presents with a 2 year history of gradually reducing mobility. Clinical examination of the patient demonstrates parkinsonism.

(a) Name 3 cardinal motor features of parkinsonism?

Answer 20

• Rest tremor
• Bradykinesia
• Rigidity
• Postural instability

Question 21

(b) Clinically you diagnose Parkinson’s disease. Name 3 other possible causes of parkinsonism.

Answer 21

• Parkinson plus disorders: progressive supranuclear palsy, multiple systems atrophy, corticobasal degeneration;
• Dementia with Lewy bodies
• Cerebrovascular disease
• Drug-induced: neuroleptics (eg. chlorpromazine, haloperidol), anti-emetics (eg. metoclopramide, prochlorperazine), sodium valproate, lithium, tetrabenazine;
• Toxins: manganese, MPTP;
• Miscellaneous: Wilson’s disease, normal pressure hydrocephalus, post-encephalitic parkinsonism;

Question 22

(c) List 2 non-motor symptoms of Parkinson’s disease.

Answer 22

• Neuropsychiatric: Depression, anxiety, dementia;
• Autonomic: Constipation, urinary disturbance, erectile dysfunction, excess salivation / sweating, postural hypotension;
• Sleep: REM sleep behaviour disorder, restless legs syndrome, daytime somnolence;
• Other: Hyposmia, fatigue, pain and sensory symptoms.

Question 23

(d) You decide to prescribe levodopa for the patient. List 1 early and 1 chronic side effects of levodopa therapy

Answer 23

Early:

Dopaminergic – nausea & vomiting, confusion / hallucinations, postural hypotension.

Chronic:

Motor complications – on / off fluctuations, levodopa-induced dyskinesias.