Myasthenias

Question 1

what autoantibodies are seen in myasthenia gravis and Lamert-Eaton myasthenic syndrome?

Answer 1

against AChR, MuSK and LRP4 on post synaptic neurone.

Antibodies against presynaptic voltage-gated calcium channels.

Question 2

What conditions are associated with MG and Lambert Eaton syndrome?

Answer 2

MG: autoimmune manifestations and thymic hyperplasia or thymoma.

Lambert Eaton: small cell line carcinoma (S-CLC)

Question 3

what is the most common ocular presentation in MG? What do Bulbar muscles control and what is most dangerous muscles that MG affects?

Answer 3

ocular manifestations often asymmetric.
Bulbar muscles control chewing and swallowing and speech.
most dangerous muscles are intercostals (respiratory effects not normally clinically isolated)

Question 4

What infections can bulbar muscle weakness lead to?

Answer 4

Aspiration and respiratory infections.

Question 5

which age and gender group is MG more prevalent in?

Answer 5

In females and older generation incidences are increasing whilst the number for child cases same.

Question 6

What might you also suspect if someone has MG?

Answer 6

Clinically silent thymoma.

Question 7

What kind of Ab associated with AChR and MusK Ab?

Answer 7

ACHR: IgG1 and 3)
MuSK: IgG2 and IgG4

Question 8

What are MusK MG patients more and less likely to present with?

Answer 8

More likely to present with generalised MG, less likely to be ocular MG.

Question 9

3 kinds of mechanisms of action of ACHR MG?

Answer 9

Ab binding and blocking
Ab binding and endocytosis
Ab binding and complement activation- end plate damage and flattening.

Question 10

How do MuSK IgG2 and IgG4 antibodies affect ACHR clustering?

Answer 10

Bind to MuSK and prevenitng interaction with LRP4. Agrin can no longer bring LRP4/MusK complexes together.
No longer phosphorylation of DOK7 and no clustering of ACHR via rapsyn.

Question 11

Which has associations with thymus pathology, MG with ACHR or MUsK Ab?

Answer 11

ONly ACHR ab associated with thymoma, not for MusC.

Therefore Musk MG won’t respond to thymectomy.

Question 12

Difference in ACHR and MusK response to steroids and immunosuppression and plasma exchange?

Answer 12

very good response to immunosuppression for ACHR, variable for MuSK.

good and very good response to plasma exchange for ACHR and MuSK

Question 13

How might LRP4 ab cause pathology?

Answer 13

a similar mechanism to MUSK.

Question 14

Which MG is bulbar weakness more commonly seen?

Answer 14

in MuSK ab.

Question 15

What are characterisitc feautres of hyperplasia in thymus?

Answer 15

LN like structure with germinal centres in the medulla.

GC surrounded by myoid cells.

Question 16

What are myoid cells surrounding GCs in thymic hyperplasia like and what do they express?

Answer 16

muscle-like ceslls expressing ACHR- role in triggering ACHR autoantibodies.

Question 17

What might you see in MG patients when you do a repetitive nerve stimulation test?

Answer 17

reduced result for this.

Question 18

What can you use to inceresae Ach in synpase in MG patients?

Answer 18

anticholinesterase agents.

Question 19

Immune suppression treatments for MG patients?

Answer 19

steroids, and immunosuppressants
rituximab
IVIG and PLEX.
thymectomy
anti FCR?

Question 20

Which form of MG responds better to rituximab?

Answer 20

MuSK Ab MG (because ACHR pathology may be caused more by CD20- plasma cells? and Musk by CD20+ plasmablasts?)

Question 21

Specific treatments for ACHR form of MG?

Answer 21

anti C5- complement inhibitors.
thymectomy.
proteasome inhibitors.

Question 22

What do thymomas and thymus in late onset of MG lack expression of?
What other autoantibodies is this associated with?

Answer 22

AIRE, which may have implications for autoimmunity.

Also associated with anti IFNa/Il-12 ab- infections?