L22 - CNS Channelopathies - Episodic Ataxia

Question 1

What is episodic ataxia?

Answer 1

• A number of different inherited conditions associated with a loss of co-ordination,
• Irregular and uncontrolled muscle contractions.
• 2 types

Question 2

What are the general symptoms of episodic ataxia?

Answer 2

• Trunk Instability
• Dizziness
• Veritgo
• Vomitting
• Blurry vision
• Headache

Question 3

Type 1 Episodic Ataxia

Answer 3

• TRiggered by physical or emotional stress
• Abrupt change in position.
• Onset is 10-20 years
• Autosomal dominant

Question 4

What casues type 1 Episodic ataxia?

Answer 4

• A KCNA1 channel mutation
• Loss of function mutation
• K+ KCNA1 cahnnel is highly expressed in the cerebellum and neuromuscular junction.

Question 5

What are possible treatments for Type 1 episodic ataxia?

Answer 5

• Acetozolamide - a carbonic anhydrase
  inhibitor.
• Phenytoin and carbamazepine - Na+ channel inhibitors

Question 6

Type 2 Episodic Ataxia

Answer 6

• Triggered by physical or emotinal stress
• Autosomal dominant
• Onset is child to teens

Question 7

What casues type 2 episodic ataxia

Answer 7

• A mutation in the CACNA1N channel, which causes reduction in the Ca+ influx.
• Resulting in problems with neurotransmitter release and controlling skeletal muscle.

Question 8

What are the 3 allelic disorders associated with CACNA1N mutations?

Answer 8

• Missense mutations - familial hemilegic
  migraine
• Spinocerebellar ataxi type 6 - repeat
  expansion C terminus.
• Clear mutation position & type determines phenotype.

Question 9

Where are CACNA1N channels located?

Answer 9

• In the purkinje and granule cells of the cerebellum.
• Also in cell bodies of the neurones