Clinical 4: Parkinsons Disease

Question 1

What is Parkinsons?

Answer 1

Parkinson’s disease (PD) is a long-term degenerative disorder of the CNS that mainly affects the motor system.

• Insidious assymetrical onset
• More common with advancing age (3% >65yrs)
• Only 8% of those with Parkinson’s disease develop it before 40
• 13yrs average between diagnosis and death (a relentless process)

Question 2

What are the cardinal clinical features? (TRAB)

Answer 2

• Rest or Re-emergent/postural Tremor
• Rigidity (non-swinging arms when walking, cogwheel rigidity)
• Postural Abnormalities: (difficulty arising from a chair, stooped posture, takes several steps to turn)
• Bradykinesia/slowness of movement (impassive face, abnormal gait, shortened stride, freezing)

Question 3

What is bradykinesia Decrement

Answer 3

A specific type of Bradykinesia.

Big amplitude movement that decrease!

Question 4

Cogwheel Rigidity

Answer 4

Abnormal rigor in muscle tissue characterized by jerky movments when the muscle is passively stretched.

Noticably in wrist.

Question 5

What do you need to make a diagnosis?

Answer 5

• 2 or more cardinal features
• Progressive symptoms
• Response to ‘levadopa’
• When there’s no alternative cause of symptoms

Question 6

What’s the pathology of Parkinsons Disease?

Answer 6

• Degeneration of dopamergic neurons in the substantia nigra.
• Presense of ‘Lewy Bodies’ also in the substantia Nigra; containing a-synuclein

Question 7

What is the Pathogenesis of Parkinsons Disease?

Answer 7

An ideopathic disease (unknown)

Genetic Susceptibility: gene mutation on chromosome 4 cause an early-onset, hereditary form of Parkinsons. Causes too much a-synuclein.

Toxins: MPTP-Parkinsonism (from wrongly made heroin)

Infections: Von Economo’s encephalitis ⇒ parkinsonism

Question 8

What drug treatments for parkinsons are out there?

Answer 8

No cure! Only symptomatic treatments available! (these ‘replace’ the deficient dopamine but nothing can stop the loss of dopaminergic neurons)

• Levodopa + dopa decarboxylase inhibitor (dopamine precursor that can cross the BBB to the brain)
• Dopamine Agonists
• Anticholinergics

Question 9

What surgical treatments are available for Parkinsons?

Answer 9

• Stereotactic thalamotomy (for tremor)
• Stereotactic pallidotomy (improves all features of parkinson’s incl. dyskinesia)
• Transplantation of dopamine-producing tissue (eg; fetal stem cells)
• Deep brain stimulation (inhibits overactive neurons non-invasively)

Question 10

Why is stereotactic pallidotomy preffered over thalamotomy?

Answer 10

The thalamotomy is in a smaller area (so dangerous) and it only reduces tremor symptoms.

Pallidotomy improves all TRAP features of Parkinsons, and is done to the globus pallidus of the STN, when the patient is awake, using a grid like structure. The patient has to be awak to know you are not affecting the internal capsule

Question 11

Deep Brain Stimulation

Answer 11

Electrodes inserted and connected to a stimultor to rebalance the basal ganglia circuit.

treats motor fluctuations and dyskinesia

**only a minority of patients candidates for this!

Question 12

Some of the late complications of Parkinsons are?

Answer 12

• Cognitive Abnormalities: confusion, hallucinations, dementia (lewy bodies)
• Emotional disturbances: anxiety, depression
• Postural Hypotension
• Fluctuations of too much/not enough dopamine: (50% of patients five years post treatment): as the disease progresses the time-slot of treatment decreases

Question 13

How can we decrease fluctuations?

Answer 13

1. Duadopa: Pump+tube into the duodenum at a small level/dose
2. Luadopa: H₂SO₄ + morphine is a dopamine agonist, pumped into the fat under the skin.