MNP - junctionopathy

Question 1

What is the particularity of repetitive nerve stimulation in CHAT myasthenic syndrome?

Answer 1

High frequency conditioning train requires to observe decremental response

Question 2

What is the key concept to differentiate focal from generalized myasthenia gravis?

Answer 2

Focal involve skeletal muscle group(s) that does not involve appendicular skeletal muscle
-> facial, esophageal, pharyngeal, and laryngeal skeletal muscles

Generalized involve appendicular skeletal muscle weakness, which can range from mild to severe, with or without facial, esophageal, pharyngeal, or laryngeal skeletal muscle involvement.

Question 3

What are the 4 structures that can be implied in focal MG?

Answer 3

Following skeletal muscles:
Facial
Oesophageal
Pharyngeal
Laryngeal

Question 4

What are the 4 subtypes of generalized MG?

Answer 4

Non-thymoma associated

Thymoma associated

Thiourylene medication associated (only cats)
- Carbimazole
- Methimazole
Reversible (excellent outcome)

Seronegative (only dogs)

Question 5

What is the rate of one-year mortality in dogs with MG? Cats?

Answer 5

Dogs: 40-60%
Cats: 15%
In cats with generalized non-thymoma MG without megaoesophagus: 100% survival

Question 6

What is the particularity for RNS in presynaptic CMS?

Answer 6

Preceding high frequency conditioning required before slow RNS to show decrement

A period of exercise is required before skeletal muscle weakness and fatigability: at that time, palpation can identify hypertonicity

Question 7

What is the treatment of presynaptic CMS?

Answer 7

Guanidine
3,4-diaminopyridine (3,4-DAP)
increase Ach in synaptic cleft

Question 8

What are the cause for false-negative MG?

Answer 8

Too early (no seroconversion)
Corticosteroids
Damage to the antigenic epitopes during solubilization
Majority of Ab bound in the skeletal muscle
Autoantibodies being direct against toxin binding site

Question 9

What is the proportion of MG cats with megaoesophagus?

Answer 9

37-50%

Question 10

Breeds predisposed to congenital myasthenia gravis

Answer 10

Springer spaniel
Jack Russell terrier
Miniature Dachshund (may regress spontanously at 6 months)
Samoyed
Smooth haired fox terrier (predisposed to concomitant megaesophagus)
Old danish pointing dog

Question 11

What is the classification of congenital myasthenic syndromes and cite one mutation in each category ?

Answer 11

Presynaptic: CHAT
Synaptic: COLQ
Postsynaptic: CHRNE

Question 12

What is the reaction catalyzed by creatine kinase?

Answer 12

ADP + phosphocreatine -> creatine + ATP

Question 13

True or false: seronegative myasthenia gravis has been described in cats.

Answer 13

false

Question 14

What are the 2 striational autoantibodies that can be found in dogs with myasthenia gravis?

Answer 14

Anti-titin receptors
Anti-ryanodine receptors

Attention: only in seropositive dogs for AChR, mainly non-thymoma associated, but also some thymoma-associated.
Not in cats!

Question 15

True or false: Positive serum antibodies against AchR are found in thiourylene associated myasthenia gravis.

Answer 15

True

Question 16

What is the incidence of a concurrent cranial mediastinal mass in dogs and cats with MG?

Answer 16

Dogs: 3.4%
Cats: 52%

Question 17

In which congenital myasthenic syndrome AChE inhibitors cannot be used ? What is a proposed treatment?

Answer 17

COLQ
Albuterol (beta2 adrenergic receptor agonist) -> stabilize NMJ and decrease AChR dispersion
Note: 3,4-DAP and AChE-I worsen signs

Question 18

What are the conditions to evoke seronegative myasthenia gravis?

Answer 18

General and neurological examination, pharmacologic, and electrophysiologic findings consistent with MG
Normalization of clinical signs after AChE-I treatment
Serum AChR autoantibody testing by radioimmunoassay to have been negative at least twice.

Question 19

For each congenital myasthenic syndrome in dogs and cats, give: affected NMJ component, mechanism of defect, protein, gene, species/breeds.

Answer 19

Presynaptic
Defect in ACh synthesis
ChAT = choline acetyltransferase
CHAT
Dogs: Old Danish Pointing dogs

Synaptic
AChE deficiency
Collagen-like tail subunit of asymmetric AChE
COLQ
Dogs: Labrador, Golden – Cats: Devon Rex, Sphynx

Postsynaptic
AChR deficiency
Acetylcholine receptor subunit epsilon
CHRNE
Dogs: Jack Russell Terrier, Heideterrier

Question 20

What are the specific features of COLQ mutation in cats compared to dogs?

Answer 20

Later onset (3-23 weeks vs. 2-8 weeks in dogs)

Decrease skeletal muscle mass
Dorsal protrusion of scapulae
Dystrophic changes
EMG changes (PSW, CRD)

RNS can be within normal limits
Normal postsynaptic AChR concentration

Question 21

cite drugs that can alter neuromuscular function

Answer 21

Lidocaine, gentamicin
Procaine, metronidazole
Tetracyclines

Question 22

Which are the 2 positive and 2 negative factors associated with clinical remission in dogs with MG?

Answer 22

Positively associated with clinical remission
Younger age
Comorbid endocrine disease

Negatively associated with clinical remission
Initial AChR Ab concentration
Regurgitation

No clinical improvement: 29%

Question 23

AchR are permeable to

Answer 23

Na+ and K+

Question 24

% megaoesophagus in aquired myasthenia gravis in dog

Answer 24

dog: 90%
rare in congenital form

Question 25

breed with congenital myasthenia with spontaneous remission and with good prognosis

Answer 25

smooth haired miniature dashund Devon Rex and Jack can survive years

Question 26

Post synaptic congenital myasthenia gravis

Answer 26

Jack Russel, Heiredale T mut **CHRNE** (cholinergic recept nicot epsilon) onset **6-8w** decrement, **dim AchR** **improvement with AchE inhib but dev resistance** **Heideterrier < 1w affected initially TL**

Question 27

synaptic congenital myasthenia gravis

Answer 27

**Labrador, Golden, Sphinx, devon Rex** mut **acetylcholinesterase** (COLQ). Onset **2-3w**. Decremental resp, **marginaly decrease AchR**. **Worsening with pyridostigmine/edrophoium**. Improvement in Golden with **albuterol**. (bet2ago) In cat musc atrophy, protrusion scapulae, PSW and complex rep discharge at EMG. Dystrophic change in m biopsy, normal AchR.

Question 28

presynaptic congen myasthenia gravis

Answer 28

**Old Danish Pointing dog** (Gammel Dansk Honsehunds) mutation **choline acetyltransferase** (CHAT) -> synthesis of ACh. Onset **12-16w**. decrement only after **high freq stim**. Treat: **guanidine** in human 3,4-DAP (diaminopyridine) **no improvement with AchEi**

Question 29

cat treatment associated with myasthenia gravis devt

Answer 29

methimazole (antib AchR)

Question 29

diagnosis myasthenia gravis % seronegative dog

Answer 29

immunoprecipitation radioimmunoassay ab anti AchR can be normalised with 1 w corticoids 2% seroneg edrophonium chloride test/neostigmine methylsulfate decrement, single fiber electromyography

Question 30

treatment and % remission dog myasthenia

Answer 30

pyridostigmide bromide, neostigmine bromide 89% remission at an average 6m

Question 31

cat/dog breeds predisposed to aquired myasthenia

Answer 31

cat: Somali Abyssian dog: Akita, Sccottish terrier, german shorthaired pointer, Chihuahua

Question 32

% cranial mediastinal mass in cat with aquired myasthenia gravis

Answer 32

52% 98% tymoma 2% lymphoma clinical outcome not associated with presence mass clinical outcome did not differ between surgical or medical treat

Question 33

factors associated with clinical remission of myasthenia

Answer 33

younger age comorbid endocrine disease negativ ass: initial AchR ab concent, regurgitation