Management of Parkinson's Disease

Question 1

What causes the motor symptoms of PD

Answer 1

A result of the loss of dopaminergic projections from the substantia nigra pars compacta to the striatum

Question 2

Levodopa

Answer 2

Prodrug of DA
Converted to DA by dopa-decarboxylase (present in CNS and PNS)
Most potent symptomatic treatment for PD motor symptoms
Administered with a dopa decarboxylase inhibitor to minimize peripheral side effects

Question 3

DA agonists

Answer 3

Directly stimulate post-synaptic DA receptors
Provide moderate symptomatic benefit, can be used alone or as adjunctive
Risk of impulse control disorders (D3 receptor)
Ex: Pramipexole, ropinirole, rotigotine

Question 4

MAO-B inhibitors

Answer 4

Inhibit the metabolism of endogenous and exogenous DA by MAO-B
Provide weak symptomatic benefit, extend duration of action of levadopa (need DA to work)
Monotherapy in early disease, then adjunctive
Ex: selegiline, rasagiline, safinamide

Question 5

Amantadine

Answer 5

Mild symptomatic benefit for the motor symptoms of PD, especially tremor
Also effective for dyskinesias
Monotherapy (early) or adjunct

Question 6

Anticholinergics

Answer 6

Useful for the treatment of tremor in PD
Use is limited by its side effects, and possible increased risk of dementia with long term use
Only useful for cognitively intact patients with young onset

Question 7

COMT inhibitors

Answer 7

Block the metabolism of DA by COMT
Must be done in conjunction with levodopa
Important side effect is orange urine
Ex: entacapone

Question 8

What is the problem with abrupt withdrawal of levodopa/DA agonists fro patients with advanced PD?

Answer 8

Can precipitate a neuroleptic-malignant syndrome-like condition that is life threatening

Question 9

What intervention is neuroprotective?

Answer 9

Physical activity (cardio, strength, balance)

Question 10

4 examples of motor fluctuations

Answer 10

Wearing off
Delayed kicking in
Freezing of gait
Off dystonia

Question 11

Wearing off

Answer 11

Generally begins as end-of-dose failure
< 4 hour duration of an adequate dose of levadopa
Offs become deeper and more severe with disease progression

Question 12

Delayed kicking in

Answer 12

Taking > 30 mins for a dose of levodopa to start working
Especially common for the first AM dose
Due to delayed gastric emptying, constipation, or poor constipation from competition with aas

Question 13

Off-period dystonia

Answer 13

Commonly occurs in the early morning when plasma levodopa is low
Usually manifests as leg cramps +/- toe curling
Can be treated with any of the meds

Question 14

Dyskinesias

Answer 14

Abnormal, involuntary movements related to dopaminergic therapy
May be ballistic, choreiform, or dystonic
Can be at peak dose, or diphasic (D-I-D)
Use lowest effective dose
Amantadine is best treatment

Question 15

How do you treat

1. Peak dose dyskinesia
2. Diphasic dyskinesia

Answer 15

1. Smaller, more frequent doses

2. Like wearing off (increase dose)

Question 16

Freezing of gait

Answer 16

Occurs more commonly when off (treat as per wearing off)
Droxidopa shows modest improvement, also levo/carbi intestinal gel
Physio and sensory tricks can help

Question 17

Pallidotomy

Answer 17

Mainly historical significance
Involves lesioning the GP to improve motor symptoms
Mechanism not well understood - disruption of disordered pathways
Mostly replaced by DBS

Question 18

Levodopa/carbidopa intestinal gel

Answer 18

Continuous infusion via PEG-J

Results in less fluctuations, improvement in dyskinesias and possible improvement in freezing of gait

Question 19

Deep brain stimulation

Answer 19

DBS of GPi and STN
Mimics the best “on” state of the patient and does not treat levodopa unresponsive symptoms
STN is most favored (can reduce medication dose)
Generally reserved for younger, cognitively intact patients

Question 20

Non-motor symptoms

Answer 20

Occur almost universally and tend to have a greater impact on QoL than motor
May fluctuate independently of motor
Non-motor fluctuations an be managed with the same strategies as motor fluctuations
Non-fluctuating non motor symptoms are managed in the same way as someone without PD