MNP - junctionopathy Flashcards
What is the particularity of repetitive nerve stimulation in CHAT myasthenic syndrome?
High frequency conditioning train requires to observe decremental response
What is the key concept to differentiate focal from generalized myasthenia gravis?
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.
What are the 4 structures that can be implied in focal MG?
Following skeletal muscles:
Facial
Oesophageal
Pharyngeal
Laryngeal
What are the 4 subtypes of generalized MG?
Non-thymoma associated
Thymoma associated
Thiourylene medication associated (only cats)
- Carbimazole
- Methimazole
Reversible (excellent outcome)
Seronegative (only dogs)
What is the rate of one-year mortality in dogs with MG? Cats?
Dogs: 40-60%
Cats: 15%
In cats with generalized non-thymoma MG without megaoesophagus: 100% survival
What is the particularity for RNS in presynaptic CMS?
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
What is the treatment of presynaptic CMS?
Guanidine
3,4-diaminopyridine (3,4-DAP)
increase Ach in synaptic cleft
What are the cause for false-negative MG?
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
What is the proportion of MG cats with megaoesophagus?
37-50%
Breeds predisposed to congenital myasthenia gravis
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
What is the classification of congenital myasthenic syndromes and cite one mutation in each category ?
Presynaptic: CHAT
Synaptic: COLQ
Postsynaptic: CHRNE
What is the reaction catalyzed by creatine kinase?
ADP + phosphocreatine -> creatine + ATP
True or false: seronegative myasthenia gravis has been described in cats.
false
What are the 2 striational autoantibodies that can be found in dogs with myasthenia gravis?
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!
True or false: Positive serum antibodies against AchR are found in thiourylene associated myasthenia gravis.
True
What is the incidence of a concurrent cranial mediastinal mass in dogs and cats with MG?
Dogs: 3.4%
Cats: 52%
In which congenital myasthenic syndrome AChE inhibitors cannot be used ? What is a proposed treatment?
COLQ
Albuterol (beta2 adrenergic receptor agonist) -> stabilize NMJ and decrease AChR dispersion
Note: 3,4-DAP and AChE-I worsen signs
What are the conditions to evoke seronegative myasthenia gravis?
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.
For each congenital myasthenic syndrome in dogs and cats, give: affected NMJ component, mechanism of defect, protein, gene, species/breeds.
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
What are the specific features of COLQ mutation in cats compared to dogs?
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
cite drugs that can alter neuromuscular function
Lidocaine, gentamicin
Procaine, metronidazole
Tetracyclines
Which are the 2 positive and 2 negative factors associated with clinical remission in dogs with MG?
Positively associated with clinical remission
Younger age
Comorbid endocrine disease
Negatively associated with clinical remission
Initial AChR Ab concentration
Regurgitation
No clinical improvement: 29%
AchR are permeable to
Na+ and K+
% megaoesophagus in aquired myasthenia gravis in dog
dog: 90%
rare in congenital form
breed with congenital myasthenia with spontaneous remission
and with good prognosis
smooth haired miniature dashund
Devon Rex and Jack can survive years
Post synaptic congenital myasthenia gravis
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
synaptic congenital myasthenia gravis
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.
presynaptic congen myasthenia gravis
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
cat treatment associated with myasthenia gravis devt
methimazole (antib AchR)
diagnosis myasthenia gravis
% seronegative dog
immunoprecipitation radioimmunoassay ab anti AchR
can be normalised with 1 w corticoids
2% seroneg
edrophonium chloride test/neostigmine methylsulfate
decrement, single fiber electromyography
treatment and % remission dog myasthenia
pyridostigmide bromide, neostigmine bromide
89% remission at an average 6m
cat/dog breeds predisposed to aquired myasthenia
cat: Somali
Abyssian
dog: Akita, Sccottish terrier, german shorthaired pointer, Chihuahua
% cranial mediastinal mass in cat with aquired myasthenia gravis
52%
98% tymoma 2% lymphoma
clinical outcome not associated with presence mass
clinical outcome did not differ between surgical or medical treat
factors associated with clinical remission of myasthenia
younger age
comorbid endocrine disease
negativ ass: initial AchR ab concent, regurgitation
