37: NMJ disorders

Question 1

What Ab’s would be present if a patient with myasthenia clinically does not have Ab’s to AChR?

Answer 1

Muscle-specific tyrosine kinase (MuSK);
low-density lipoprotein receptor-related protein 4 (LRP4)

Question 2

What are the most common types of weakness in MG?

Answer 2

Extra-ocular;
bulbar (difficulty with swallowing, chewing, and speaking) with nasal and slurred speech

Question 3

What is seen in folks with anti-MuSK Ab-associated MG? Who does it tend to affect?

Answer 3

Younger females;
look for severe oculobulbar weakness along with tongue and facial atrophy, with tongue fasciculations;
look for neck, shoulder, and respiratory weakness with little or no ocular weakness;
or you see a pattern similar to anti-AChR Ab-associated MG

Question 4

What test can improve ptosis with MG?

Answer 4

Ice pack test

Question 5

In what condition can MG be seen as a rare complication?

Answer 5

Cancer patients treated with immune checkpoint inhibitors

Question 6

What can immune checkpoint inhibitors lead to?

Answer 6

Myasthenia, myositis, GBS, CIDP

Question 7

How to treat MG provoked by ICPI’s?

Answer 7

Plasmapharesis and high-dose steroids; need to stop the drug

Question 8

Other causes of autoimmune MG?

Answer 8

Transient neonatal MG and penicillamine treatment

Question 9

Major difference between LEMS and MG on NCS?

Answer 9

Low CMAP amplitude for LEMS typically

Question 10

Diagnostic yield of MG on RNS increases with what nerves stimulated?

Answer 10

Proximal nerves, as proximal muscles usually involved more than distal

Question 11

What should be done if there is no significant decrement on RNS studies at baseline?

Answer 11

Exercise testing (1 min of exercise, then RNS at 1-min intervals for the next 3-4 mins, looking for CMAP decrement with post-exercise exhaustion)

Question 12

What do MUAP’s look like with NMJ disorders?

Answer 12

Unstable, small and short-duration, or both

Question 13

What is the clinical correlate of blocking?

Answer 13

Muscle weakness

Question 14

What is an advantage of SFEMG or RNS?

Answer 14

Can show increased jitter even without clinical weakness

Question 15

What filter settings change with SFEMG? What is the distance single-fiber muscle action potential need to be to be recorded for SFEMG?

Answer 15

Low freq filter increased to 500-1000 Hz;
200-300 um, to only catch single muscle fibers close to the needle

Question 16

What is necessary to deem the upper limit of jitter of a muscle abnormal? How to make a diagnosis of NMJ disorder?

Answer 16

More than 10% of the pairs studied must exceed the upper limit of normal;
Mean jitter must be abnormal, or ULN jitter must be abnormal in more than 10% of individual pairs

Question 17

Increased _____ is consistent with an NMJ disorder;
when does blocking typically occur?

Answer 17

jitter;
mean consecutive difference (measure of jitter) is more than 80-100 us

Question 18

What is the most sensitive test to demonstrate impaired NMJ transmission?

Answer 18

SFEMG

Question 19

Pathogenesis of LEMS?

Answer 19

Immune-mediated;
look for IgG Ab’s directed at presynaptic P/Q and N-type voltage-gated Ca channels

Question 20

What is seen with LEMS clinically not usually seen with MG?

Answer 20

DTR’s usually reduced or absent

Question 21

With slow RNS before and after exercise in LEMS, what happens with decrement and the baseline CMAP?

Answer 21

Decrement in both places;
however, baseline CMAP larger post-exercise than pre-exercise

Question 22

What trick can be used if patient has low or borderline low CMAP amplitude at rest and you suspect LEMS?

Answer 22

Repeat the distal motor stim after 10 seconds of maximal exercise, looking for post-exercise facilitation of the CMAP

Question 23

What are CMAP amplitudes in botulism? How does the increment compare after brief exercise or fast RNS?

Answer 23

Low, like LEMS;
increment is present, but not as much as LEMS

Question 24

What is seen spontaneous activity wise and on SFEMG for botulism?

Answer 24

Fibs and PSW’s;
Increased jitter and blocking

Question 25

With congenital myasthenic syndromes, what muscles are affected mostly?

Answer 25

Extraocular, bulbar, and proximal muscles

Question 26

What is the most common subgroup of congenital myasthenic syndromes (CMS)?

Answer 26

Postsynaptic CMSs more common than AChase deficiency, more common than presynaptic CMSs (post > AChase > pre)

Question 27

What mutations account for most CMSs?

Answer 27

DOK-7 (activator of MuSK essential for formation of the NMJ; simplified postsynaptic membrane) and RAPSN (reduced number and density of AChR’s)