Parkinson's Disease

Question 1

EPIDEMIOLOGY

Answer 1

• 0.1%
• 2x more common in men
• rare <50, affects 1.5% 70-79y, 3.5% >80y.

Question 2

CLINICAL FEATURES:

1. TRAP
2. Early symptoms
3. Tremor(70% untreated pts)
4. Rigidity
5. Face and speech
6. Posture and gait
7. Cognition
8. Psychiatric

Answer 2

1. Tremor, Rigidity, Akinesia/Bradykinesia, Postural instability
2. Difficulty in fine movements(micrographia), tremor, feeling of slowing down
3. Characteristically unilateral onset, typically resting tremor affecting hands. 3-5 Hz, pill-rolling.
4. Most evident in elbow and wrists, cogwheeling. lead pipe
5. Face immobile(mask-like), drooling, dysarthria w monotonous voice
6. Stooped, loss of arm swing, short steps, difficulty starting/stopping, loss of postural reflexes
7. Bradyphrenia later in disease, >25% progress to dementia.
8. Depression(about 40%), psychosis, sleep disturbances

Question 3

DDx:

Answer 3

1. Essential tremor:
   - more prominent on sustained posture/movement. no resting tremor.
   - yes-yes head tremor/titubation/trombone tremor of tongue
2. Unilateral hemiparesis
3. Muscular/rheumatic diseases(muscle stiffness)
4. Malignancy
   - fatigue and weight loss
5. Depression
   - slowness of thought and actions
6. Diffuse cerebrovascular disease
   - ‘marche à petit pas’
7. Normal Pressure Hydrocephalus
   - apraxic gait
8. Drug-induced
   - phenotiazines and antipsychotics
   - motor Sx. generally rapid onset and bilat.
   - rigidity and resting tremor uncommon
9. Wilson’s disease
   - younger pts
10. Parkinson’s plus syndromes
    - rare
    - share same features but different pathological findings
11. Lewy body dementia

Question 4

PATHOLOGY AND AETIOLOGY

Answer 4

1. loss of pigmented dopaminergic cells in substantia nigra
2. Lewy bodies in remaining neurones
3. Genetic f(especially affecting mitochondrial fn) and env f.

Question 5

INVESTIGATIONS

Answer 5

1. Primarily clinical Dx.
2. Head CT/MRI to exclude NPH/small vessel disease
3. isotope DAT distinguishes btw Parkinsonism and essential tremor or drug-induced Parkinsonism

Question 6

DRUG TX

Answer 6

1. Levodopa preparations
   - Sinemet, Madopar
   - Sinemet CR, Madopar CR
   - reduced effectiveness w time.
   - dyskineisa, on-off effect, dry mouth, anorexia, palpitations, postural hypotension, psychosis, drowsiness
2. Dopamine agonists
   - SE: nausea, dizziness, confusion, sleepiness(excessive daytime sleepiness), altered behaviour(impulse control behaviour), can cause hallucinations in older pts, postural hypotension, nasal congestion
   - Bromocriptine(ergot-derived), Lisuride(broad-spectrum)
   - Ergot ie Pergolide, Cabergoline(more specific to D2 dopamine R); can cause cardiac valvular fib, pulm., retroperitoneal fibrosis.
   - Non-ergot ie apomorphine, ropinirole, pramipexole(SC pump), Rotigotine(patch)
3. Amantadine
   - Dopamine releasing agents
   - weak symptomatic effects, helps dyskinesia
   - SE: ataxia, confusion, slurred speech, dizziness, livedo reticularis.
4. MAO type B inhibitor
   - selegiline, rasagiline
   - mild symptomatic effect, smoothens delivery of levodopa
5. COMT inhibitor ie entacapone
   - augments levodopa effect
6. Anti-Ch
   - Benztropine, procyclidine, trihexyphenidyl(benzhexol)
   - useful for tremor, rigidity prominent adverse effects
   - used more in drug-induced parkinsonism.

Question 7

THERAPEUTIC NOTES

Answer 7

1. Delay tx until disabling Sx. onset.
2. Levodopa and dopamine agonists for severe disease.
   - <70y, dopamine agonist and if >70y, levdopa
3. Before initiating ergot-derived dopamine agonists: echo, CXR, ESR, creatinine.
4. Levodopa used together w decarboxylase inhibitor(carbidopa/benserazide)
   - prev peripheral metab. of levodopa to dopamine

Question 8

COMPLICATIONS OF TX

• 75% pts after 5y
• due to resistance to levodopa and narrowed therapeutic window

Answer 8

a) Fluctuations
- increase freq. of doses
- smoothen levodopa through MAO type B inhibitor/COMT inhibitor/dopamin agonist/CR levodopa

b) Dyskinesia
- chorea+athetosis; severe, painful dystonia
- smoothen levodopa, reduce levodopa doses. dopamine agonist or with amantadine

c) Drug failure
- gradual increase in loss of postural stability.

Question 9

OTHER TX:

1. Depression
2. Hallucinations
3. Salivary drooling
4. Nausea

Answer 9

1. Antidepressants
2. Small dose quetiapine
3. Anticholinergics
4. Domperidone. Avoid other antiemetics.