Myasthenia

Question 1

Where is affected here

Answer 1

Neuromuscular junction

Question 2

Which ones are acquired?

Answer 2

Myasthenia gravis

Transient neonatal myasthenia gravis (born to mothers with MG)

Infantile botulism

Question 3

Which one is congenital?

Answer 3

Congenital myasthenic syndromes

Question 4

Give some general info on autoimmune myasthenia

Answer 4

Acetylcholine receptor antibody - ocular and generalised

Fatigue

Isolated ptosis and ocular weakness

Crisis: Respiratory and bulbar - dysarthria/nasal speech

Question 5

Investigations in autoimmune myasthenia

Answer 5

AChR abs

Anti MUSK abs

Receptive nerve stimulation

Question 6

Treatment for autoimmune myasthenia

Answer 6

Pyridostigmine

Prednisolone

Immuno suppression

Plasma exchange

Ventilation

Thymectomy

Question 7

What is infantile botulism

Answer 7

Infant botulism is caused by anaerobic bacteria

Ventilation is needed

Question 8

Give me information on presynaptic CMS

Answer 8

5% are presynaptic - CHAT (choline acetlytransferase)

Question 9

Give me information on synaptic CMS

Answer 9

10% are synaptic (basal lamina-associated)

COLQ (collagen tail of ACHE)

Question 10

Give me information on postsynaptic CMS

Answer 10

85% are postsynaptic

e subunit of ACHR - Rapsyn - Dok-7

Question 11

Slow channel

Answer 11

Most common

Autsomal dominant

Postsynaptic

Quinidine and Fluoxedine - normalise AChR opening time

Question 12

Fast channel

Answer 12

Very rare

No distinguishing factors

Treatment: Cholinesterase inhibitors and 3,4-diaminopyridine

Question 13

Low AChR expression

Answer 13

Half of all identified CMS patients

> 60 different mutations - most mutations in e subunit

Treatment: Cholinesterase inhibitors and 3,4-diaminopyridine

Question 14

MuSK-Dok7-Rapsyn pathway

Answer 14

Specific receptor thyrsine kinase

Activer by agrin released by motor neurons through LPR4

Agrin - triggers AChR collection via rapsyn

MuSK is coactivated by Dok-7

Question 15

Rapsyn deficiency

Answer 15

Neonatal/antenatal - Arthogryphosis multiplex (joint stiffness), respiratory disorder and severe progression

Mild forms in childhood and adulthood

Initially severe in infancy and may recover in adolescence

Question 16

Dok-7 myasthenia

Answer 16

Irish

LGMD phenotype

Question 17

When do Congenital Myasthenic Syndromes start

Answer 17

Childhood

Question 18

Are Congenital Myasthenic Syndromes more or less common than autoimmune MG

Answer 18

Less - 1 in 50,000 in Europe

Question 19

Currently, how many genes are responsible for CMS

Answer 19

20

Question 20

How does CMS progress in adulthood

Answer 20

It gets worse; Scoliosis

Question 21

Is CMS Autosomal recessive or dominant

Answer 21

Family history - most are Autosomal Recessive

Question 22

What triggers CMS

Answer 22

Infections

Pregnancy

Menstrual periods

Question 23

What is associated with mortality in CMS

Answer 23

Acute respiratory failure

Question 24

Treatment for CMS?

Answer 24

Favourable effect of cholinesterase inhibitors, but several types worsen with

Question 25

Are the same symptoms like fatigability and ptosis present in CMS

Answer 25

Yes, although ptosis is hard to recognise in a child

Question 26

Are reflexes preserved

Answer 26

Yes

Question 27

What does AChR antibody affect

Answer 27

Ocular and generalised

Question 28

What does Anti MUSK antibody affect

Answer 28

Bulbar and Respiratory

Question 29

What is the clinical presentation of CMS

Answer 29

Hypotonia Ophthalmoplegia Ptosis Dysphonia Dysphagia Facial paresis Muscle fatigability