Parkinson's

Question 1

What is Parkinsonism?

Answer 1

A clinical syndrome characterized by slowness and poverty of the movement, stiffness. Can have many causes: PD, secondary parkinsonism, hereditary parkinsonism, atypical parkinsonism

Question 2

What are motor symptoms of PD?

Answer 2

• Slowness and poverty of the movement
• Rigidity
• Tremor
• Postural instability (balance)
• Restless legs
• Daytime sleepiness
• Impaired sense of smell
• Sleep apnea
• pain

Question 3

What are non-motor symptoms of PD?

Answer 3

• Urinary frequence
• Anxiety
• Depression
• Deficits in memory
• Deficits in attention

Question 4

Basic mechanism of PD?

Answer 4

• Degeneration of Substantia nigra (this causes motor symptoms and apoptosis). Motor symptoms occurs after 50% of niagral cell lost and 80% after striatal dopamine lost
• Microscopic mechanism: interneuronal lewy bodies which mainly consist of alpha-synuclein, neuronal loss, gliosis
• Macroscopic mechanism: paleness of substantia nigra
• In addition to changes in substantia nigra, also changes in: cerebral cortex, hypothalamus, spinal cord, peripheral ANS etc..

Question 5

What are clinical manifestations of PD?

Answer 5

PD can also manifest as:

• Small hand writing
• Masked face/reduced blinking
• Stooped posture
• Muscle cramps

Question 6

What are the risk factors?

Answer 6

• Age (most important)
• Gender (male > female)
• Genetic factors
• Antibiotics
• Positive family history (15%)

Question 7

What are the “protective factors”?

Answer 7

• Coffee

- Smoking

Question 8

Genetics of PD?

Answer 8

• Gene mutations in SCNA, PRKN, PINK1, GBA…

- Probably heterogeneous

Question 9

Is PD inherited?

Answer 9

• PD is mostly sporadic

- Small part (15%) has positive family history and this percent increases in close relatives

Question 10

How is the PD diagnosis made?

Answer 10

The PD diagnosis is based to:

• History
• Clinical symptoms (motor + non-motor) and signs
• Exclusion of other causes
• No specific biomarkers available
• False positives up to 15%-25%

There is three (3) basic step for diagnosis of PD:
Step 1: Clinical criteria (Parkinsonism must be present! also bradykinesia and rigity or resting tremor (or both).

step 2: Exclusion criteria

Step 3: Red flags, supportive criteria

-Also neuroimaging is used as a help to diagnose PD (degeneration of substantia nigra and changes in other brain areas). It can be used to exclude other causes. PET, MRI, CT

Question 11

Treatment of PD?

Answer 11

• No therapy proven curative or disease modifying (drug therapy)
• Drug therapy: MAO-B inhibitors (inhibition of DA break down), levadopa (DA replacement, most effective), DA antagonist, COMT inhibitor (inhibition of DA break down), combinations
• Main goal of drug therapy is enhancement of striatal dopaminergic activity
• Surgical therapy (DBS) reduced motoric symptoms
• Levadopa drug therapy is most effective because its penetrated the blood-brain barrier (DA not)