Parkinson's disease

Question 1

Pathophysiology of parkinson’s

Answer 1

1. lewy body protein deposits of alpha-synuclein
2. loss of dopaminergic neurons form pars compacta of substantia nigra of the midbrain
3. degeneration also occurs in other basal ganglia nuclei

Question 2

diagnosis

Answer 2

1. clinical diagnosis by recognizing physical signs and symptoms
2. DAT imaging to assess extent of neuron loss

Question 3

early onset Parkinsons

Answer 3

strongly linked to genetic factors

1. PARK 1 gene - codes for alpha synuclein protein
   - inherited AD
   - rare but major lewy body protein
2. PARK 2 - codes for Parkin protein
   - Autosomal recessive
   - responsible for most cases of juvenile PD

Question 4

Epidemiology

Answer 4

around twice as common in men

mean age of diagnosis is 65 years

Question 5

definition of Parkinson’s

Answer 5

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

Question 6

Clinical features of parkinson’s

Answer 6

patients develop a variety of non specific symptoms prior to motor symptoms

1. anaemia (present in 90%)
2. Depression + Anxiety
3. Aches and pains
4. REM sleep behavior disorder
5. Autonomic features - urinary urgency, postural hypotension
6. Restless leg syndrome

Question 7

Bradykinesia

Answer 7

1. slowing down of movements - progressive fatiguing and reduced amplitude
   - difficulty initiating movements
   - facial immobility : mask like
   - Serpentine stare - reduced frequency of spontaneous blinking
2. Short shuffling steps with reduced arm movements

Question 8

Tremor

Answer 8

1. presenting symptom in 70% of patients
2. unilateral initially spreading to leg
3. most marked at rest - reduces in motion
4. worse whens stressed or tired
5. typically ‘pin rolling’ ie. the thumb and index finger

Question 9

Rigidity

Answer 9

1. lead pipe - stiffnes son passive limb movements

2. cogwheel rigiity - stiffness occurs with tremor

Question 10

Postural and gait changes

Answer 10

1. stooped posture is characteristic

2. shuffling gait - slow turns, reduced stride length and reduced arm swing

Question 11

Speech and swallowing

Answer 11

1. quiet, indistinct flat voice
2. drooling
3. swallowing difficulty - increased risk of aspirayion pneumonia

Question 12

Cognitive and psychiatric changes

Answer 12

1. cognitive impairment and dementia in 80% of later stages
2. visual hallucinations and psychosis
3. depression and anxiety are common

Question 13

Drug-induced parkinsonism

Answer 13

• motor symptoms are generally rapid onset and bilateral

- rigidity and rest tremor are uncommon

Question 14

Names of anti-Parkinson’s medication

Answer 14

1. Levadopa
2. Dopamine receptor agonist - Bromocriptine/Ropinirole
3. Monoamine Oxidase - B inhibitors
4. Amantadine
5. Catechol-O-Methyl Transferase inhibitors
6. Anti muscarinics

Question 15

Levodopa ( mechanism of action )

Answer 15

1. a precursor of dopamine which is used as a dopamine supplement
2. precursor needs to be used because dopamine itself cannot cross the blood-brain barrier
3. Administered alongside ‘decarboxylase inhibitor’ ( carbidopa) to inhibit decaboxylase enzyme from converting Ldopa into dopaine peripherally

Question 16

Positive effects of Levadopa

Answer 16

1. improved motor symptoms
2. improves activities of daily living
3. fewer spec adverse side effects - excess sleepiness/hallucinations etc

Question 17

Adverse effects of Levadopa

Answer 17

1. ‘wearing off effect’ no longer effective in stimulating dopamine terminals// less effective overtime
2. dyskinesia ( invol writhing movements )
   - Dry mouth
   - Anorexia
   - Palpitations
   - Drowsiness

Question 18

MOAB inibitors ( mechanism of actions )

Answer 18

1. inhibits monoamine oxidase enzyme which breaks down dopamine
2. e,g, Selegiline

Question 19

Catechol-O-Methyl Transferase

Answer 19

1. Entacapone, tolcapone
2. COMT is an enzyme which transfers methyl group onto dopamine and inactivates it
3. this enzyme is inhibited and so more dopamine is avaliable

Question 20

Dopamine receptor agonist

Answer 20

1. Bromoccriptine/ Ropinirole

Question 21

Dopamine receptor agonist - Adverse side effects

Answer 21

1. Pulmonary + Cardiac fibrosis ( obtain ECG, ECHO, ESR and Chest x RAY prior to starting)
2. impulse control disorder - complete inhibition
3. more likely to cause hallucinations

Question 22

Anti muscarinics

Answer 22

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

Question 23

management of parkinson’s

Answer 23

1. first-line treatment:
   - if the motor symptoms are affecting the patient’s quality of life: levodopa
2. if the motor symptoms are not affecting the patient’s quality of life:
   dopamine agonist (non-ergot derived),
   levodopa
   monoamine oxidase B (MAO‑B) inhibitor
3. 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
   - catechol‑O‑methyl transferase (COMT) inhibitor as an adjunct

Question 24

Amantadine

Answer 24

1. mechanism is not fully understood, probably increases dopamine release and inhibits its uptake at dopaminergic synapses
2. side-effects include
   ataxia
   slurred speech
   confusion
   dizziness and livedo reticularis