MNP - myopathies Flashcards
Which ion channel are implicated in myotonia congenita?
Chloride channel
What is the histological finding in hyperadrenocorticism myopathy?
Type II atrophy
True or false: mitotane or trilostane has limited effect on muscle stiffness.
true
muscle weakness usually resolve with HC treatment severe muscle stiffness does not
Describe the specificities of type I and II myofibers.
Type I: slow = oxidative
Type II: fast = glycogene
Cite 5 infectious agents that may cause myositis in the dog and the cat
Neosporosis
Toxoplasmosis
Leishmaniosis
B. Burgdorferi
Leptospirosis
Ehrlichia canis
Hepatozoonosis
Trypanosomiasis
Trichinosis
Sarcocystosis
Microfilariasis
Clostridiosis
FIV
Sporotrichosis
R. ricketsii
Muscles hypertrophied in dystrophin deficient muscular dystrophy in dogs? In cats?
Dogs:
Semi-tendinous
Semi-membranous
Sartorius
Tongue
Cat: all
Mutation and breed associated with inherited form of hypokaliemic myopathy
Burmese
Mutation WNK4 (proteine kinase in distal nephron)
onset 1y, some without signs, maj episodic
signs not always assoc with low K
DDX ventroflexion in cats
HypoK
Myasthenia gravis
Hypothroidism
Diabetes
Organophosphate toxicity
Thiamine deficiency
Polymyositis
Cervical ischemic myelopathy
What are the abnormalities seen during EMG in dogs with hypercortisolism-associated SMS? Which muscles are more affected?
EMG: complex repetitive discharges and occasional myotonic discharges, fibrillation potentials, and positive sharp waves
Muscles: epaxial and proximal appendicular muscles > distal appendicular muscles
DDx inflammatory myopathies
Idiopathic (presumed immune-mediated or autoimmune)
Masticatory muscle myositis
Polymyositis: diffuse, extraocular, laryngeal
Dermatomyositis
Secondary (associated with other diseases)
Infectious
- Parasitic: Neosporosis, Toxoplasmosis,
- Hepatozoonosis, Trypanosomiasis, Trichinosis, Sarcocystosis, Microfilariasis
- Bacterial: Leptospirosis, Clostridial
- Rickettsial: Ehrlichia canis
- Viral: Feline immunodeficiency virus, other viral?
- Fungal: Sporotrichosis, Systemic mycosis
Connective tissue diseases: systemic lupus erythematosus
Paraneoplastic diseases: thymoma
Drug-induced myopathy: D-penicillamine, cimetidine, trimethoprim-sulfadiazine
What stains period acid-Schiff in muscle?
Glycogen and polysaccharide
What are the 4 genes implied in centronuclear myopathy in dogs? Which breeds are related?
HACD1 = PTPLA: Labrador retriever
BIN1: Great Dane
DMN2: Border Collie
MTM1 (XL): Labrador retriever, Rottweiler, Boykin spaniels, Maine Coon
What are the 2 drugs for myotonia congenita in dogs? In cats?
Procainamide (toxic in cats)
Mexiletine
Both are Na+ channel blockers
Phenytoin
What is the molecule for provocative test of Scotty cramps?
Methysergide: competitive serotonin antagonist
The following statements are correct, except:
1. Congenital myotonia is a channelopathy
2. In cases of rhabdomyolysis, there is elevation of CK concentrations
3. CK has a shorter life compared to AST
4. Dystrophin is a protein of the sarcoplasmic reticulum
4
What is the main histopathologic feature associated with steroid-induced myopathy?
Atrophy of type II muscle fibres
What are the risk factors for limber tail syndrome in Labrador Retriever?
Swimming
working dogs
Higher latitudes
genetic predisposition
What is the most frequent cause of muscles cramp in dogs?
Hypocalcemia secondary to hypoparathyroidism
The cause of MCs was hypocalcemia in 11/14 (79%) dogs: 9 dogs were affected by primary hypoparathyrodism, 1 dog by intestinal lymphoma and 1 dog by protein losing enteropathy.
In 3/14 cases (21%) the cause was not identified, and all 3 dogs were German Shepherds.
Muscle stiffness in dog with hypercortisolism
1. Is associated with worse prognosis than dog without locomotor signs
2. Resolve with HC treatment in the majority of dog
3. Can involve masticatory muscles
3
What are the 3 patterns of muscles cramp in dogs?
Pattern I = migrating pattern: sudden onset of stiffness and abduction of 1 thoracic limb, failure to bear the weight lasting few seconds, followed by a sustained muscular contraction with flexion of 1 pelvic limb and fall in lateral recumbency
Pattern II = pelvic limbs pattern: prolonged muscular contraction and flexion of the pelvic limbs. When these dogs were forced to continue physical activity, MCs migrated between the pelvic limbs, without involvement of thoracic limbs
Pattern III =single-limb pattern: abrupt contraction and flexion of the single limb, without any migration toward other limbs
Muscle cramp is always triggered by prompting the dogs to move: true or false?
False
In only 9/14 (64%)
Muscle cramp is always painful: true or false?
True
8/14 (58%) dogs were overtly painful with 6/14 (42%) showing mild discomfort.
In canine idiopathic polymyositis the muscles most affected are:
proximal muscles
What are the 5 causes of myotonia?
Dystrophy
Non-dystrophy
Myotonia congenita: CLCN1
Pseudomyotonia: SLC7A10
Hyperkaliemic periodic paralysis: SCN4A (EQ)
Potassium aggraved myotonia
Attention: feline hypokaliemic periodic polymyopathy causes myalgia and weakness
In canine dermatomyositis the muscles most affected are:
Temporalis muscle group
Distal muscle group
How can the dogs with X-linked myopathy be identified within the first weeks of age ?
Serum CK level which may be up to 300 times normal
types of muscular dystrophy in cats
X-linked dystrophin def : Main Coon, DSH
merosin = laminin alpha2 def: Siamese, Main Coon
sarcoglycane def: DSH
specificities of muscular dytrophy in cat
muscle hyperthrophy
macroglossia + lingual calcium deposit
scalloped appearence of diaphram (thickening), megaoeso, esophageal stricture
treatment for megaoesophagus
sildenafil: phosphodiesterase inhib
type of muscular dystrophy in dog
X-linked DMD:
COL6A1 Landseer
COL6A3 in Lab, Amsatff
LARGE 1 in Lab
LAMA2 Staffordshire bull T
SCG (sarcoglycane) Boston Terrier, miniat Dashund
muscular dystrophy in Amsatff
mut COL6A3 (Ullrich-like)
onset 6m
progressive weakness, joint contracture, distal joints hyperlaxity
abnormal CK, joint effusion. EMG: PSW and fib in m bellies superficial level.
histo: variab m fiber size, atrophic fibers round shape. Sporadic necrotic fibers undergoing phagocytosis, endomysial fibrosis.
Improvement with rehab, AINS
distinction with COL6A1: distal joint laxity and angular contract, no prolonged sleeping, less severe prog
hereditary myotonia: mut, breed, histo
mut CLCN1 (Cl channel)
myotonic potential: wax and wane
muscle hypertrophy, warm-up effect
histo: varaition diam fibre
breeds: Miniat Schnauzer, Australian cattle, Lab Ret, American Bulldog, goat
diff hypokalieamia cat
decrease intake
GI losses
renal losses ( hyperlado, chronic kidney disease, diabetus mellit)
hypercoticism (iatro, one case)
hyperthyroidism
fluid overadministration, overuse od diuretic
hereditary in Burmese (WNK4)
hyperK ->hyperpolaris of sarcolemma resting pot ->refractory to depol
myopathy in Labrador
musc dystrophy: DMD, COL6A3, LARGE 1
myopath:
congenit dyserythropoiesis and polymyopathy
myotub myopathy MTM1
centronucl myopath PTPLA1
muscle biospy in centronuclear myopathy
central nuclei and dark center with sub-sarcolemmal peripheral halos with oxidative reactions
mutations for centronuclear myopathy/myotub myopathy
centronuclear:
Labrador PTPLA
Great Dane BIN1
Border Collie DNM2
myotub (X linked):
Labrador, Rottweiler, Boykin spaniel MTM1
MNP diseases in main coon
spinal muscular atrophy LIXI
myotubular myopathy MTM1
laminin deficient musc dystrophy
centronuclear myopathy
onset 1-7m
X-linked condition signs earlier, progress more rapidely and more severe signs
centralized nuceli, atrophy type II myofiber, mitochondrial aggregate
predisposition immune mediated polymyositis
Viszla
Newfoundland
Boxer
colagen 6 deficiency in labrador
6m
hypometric in all 4 limbs
Hyperfelxion of carpi, tarsi, and stifles.
Normal thoracic withdrawal and myotatic reflexes. Pelvic limb withdrawal and patellar reflexes mildly reduced.
excessive variability in myofiber size, atrophic fibers having a round shape and of both fiber types, small numbers of myofibers containing internal nuclei, endomysial fibrosis, mild to moderate mononuclear cell infiltrations, and subsarcolemmal accumulations of NADH‐TR positive material. collagen VI is present by immunostaining in the interstitium but specifically absent in the sarcolemma.
other breeds: COL6A3 American Stafford Terrier
COL6A1 Landseer
slow progression
Muscles hypertrophied in dystrophin deficient muscular dystrophy?
Dog: semi tendinous, semi membranous, sartorius, tongue
Cat: all
neoplasia associated with polymyositis
bronchogenic carcinoma, lymphoma, myeloid leukemia, tonsillar carcinoma
signs sarcocystis infection
muscular myositis and ataxia
liver injury as elevated serum enzymes and hyperbilirubinemia
Sarcocystis caninum, and Sarcocystis svanai
Dogs were either singly infected with S. caninum or multiply coinfected with S. caninum and S. svanai
limb girdle muscular dystrophy in Boston terriers/ miniature Dashnund
SGCD (sarcoglycan) in Boston SGDCA in m Dashund
inherited autosomal myopathies that preferentially affect voluntary muscles of the shoulders and hips
absence of sarcoglycan-sarcospan complex by immunostaining
Muscle wasting, dysphagia, exercise intolerance, lethargy, and failure to thrive were accompanied by progressive gait abnormalities including a short, stilted gait
muscle degenerative changes and calcific deposits
hereditary affection associated with mitochondria
subacute necrotizing encephalopathy or Leigh syndrome: SLC19A3 in Alaskan Huskies and in Yorkshire terriers; a cytochrome b variant causing canine spongiform leukoencephalomyelopathy in Australian blue heelers and Shetland sheepdogs; and a NDUFS7 variant in a Jack Russell–Chihuahua mixed-breed dog
Nuclear gene variants associated with canine mitochondrial myopathies
- PDP1 gene encoding the phosphatase enzyme that activates the pyruvate dehydrogenase complex, in Clumber and Sussex spaniels
- SLC25A12 mitochondrial aspartate/glutamate carrier gene that causes an inflammatory myopathy in Dutch shepherd dogs
- ACADVL gene encoding the very-long-chain acryl-CoA dehydrogenase associated with exercise-induced myopathy in German Hunting terriers
- mitochondrial myopathy in Old English Sheepdogs associated with reduced mitochondrial mRNA and decreased cytochrome c oxidase activities in fibroblasts and skeletal muscle
- sensory ataxic neuropathy with mut mitochondrial tRNATyr gene has been described in golden retriever dogs
- cardiomyopathy and arrhythmia have been described in a family of Rhodesian ridgeback dogs with a missense variant in the nuclear gene QIl1
- mitochondrial myopathy in standart Poodle, DYNLT1 retrogene into the nuclear genome
Mitochondrial myopathy standart poodle
Patellar reflexes were absent bilaterally and withdrawal reflexes were reduced
increase lactate pre+post exerc
DYNLT1 gene encodes an important regulator of the voltage-dependent anion channel VDAC, a gated porin that permits the transport of peptides, metabolites and ions
stain: Gomori trichrome stain can identify the presence of ragged-red fibers. variability in myofiber size. several myofibers contained internal dark blue deposits with the SDH mitochondrial-specific reaction.
Nemaline myopathy in American bulldogs
NEB (nebulin) stabilizes the actin thin filament of skeletal muscle sarcomeres
generalized muscle weakness, exercise intolerance, and tremors beginning at approximately 2 months
myopathy was relatively non-progressive
Atrophy of the cervical and
dorsal thoracic limb muscles was noted with bilateral
hypertrophy of the triceps muscles.
marked variability in myofiber size and generalized atrophy. od-like
inclusion bodies highlighted with the modified Gomori trichrome stain
Inflammatory Myopathy in Dutch Shepherd Dogs
SLC25A12 mitochondrial aspartate-glutamate transporter known as the neuron and muscle specific aspartate glutamate carrier 1. proinflammatory milieu and strong support for oxidative stress
onset 5m
Inflammatory Myopathy in the Dutch Kooiker Dog
onset 4y, death 5.5y (respond to steroids but deteriorated
dysphagia (40%), a possible (tetra)paresis/stiff gait (92%) and/or a combination of these clinical signs, dyspnea 22%, myalgia 14%
elevated CK (even in dogs with only dysphagia), 2/87 megaeso
EMG: abnormal spont act 91%
moderate-to-marked, chronic-active, diffuse, interstitial and myofibre-directed lymphohistiocytic myositis. The location of the infiltrate was mainly in the endomysium, or a combination of endomysium and perimysium. Myofiber invasion is mostly driven by CD3+>CD8+ T cells and macrophages»_space; CD20+ B-cells
No correlation was found between the type of inflammation, the severity of the inflammation and the CK activity or clinical signs.
breed** also predisposed to hereditary necrotizing myelopathy**
Polymyositis in the Hungarian Vizsla
predominantly the muscles of mastication
and only in a limited number are clinical signs of locomotion problems identified
Anticorps associated with polymyositis in Boxer/Newfoundland/Visla
Boxer dogs and Newfoundlands: sarcolemma-specific autoantibodies
Vizslas: MHC-II haplotype is associated with the disease
histopathological feature of polymyositis
Histopathological findings in PM consist of a multifocal, mixed predominantly mononuclear cell infiltration of varying severity depending on the sampled muscles and stage of the disease. Degenerative features, including myofibre diameter variations with fibre atrophy, nuclear internalization, necrosis, myofibre loss and fibrosis, and regenerative changes like nuclear rowing, compensatory hypertrophy and regenerating fibres, are frequently seen in the muscles of affected animals
inflammatory infiltrates in PM includes lymphocytes, predominantly of the T-cell type with cytotoxic CD8+ T-cells, in greater number than CD4+ T-cells, and lesser numbers of dendritic cells, macrophages, and B-cells. CD8+ lymphocytes are distributed along the endomysium surrounding necrotic myocytes and invading viable muscle fibres. In contrast, in MMM, CD4+ T-cells and B-cells are more commonly reported distribution is concentrated along the perimysium and perivascularly
Muscle Hypertrophy, Dysphagia, and Gait Abnormalities in Young French Bulldogs
CLCN1 and PDE4C
oil red 0 stain
neutral triglycerid, forlipid storage myopathy
in fatty acid oxidation disorder and carnitine deficiency
Periodic acid schiff reaction
external (basal) lamina
glycogen
myelin
for glycogen storage disorder and polysaccharide storage disorder (amylase resistant)
NADH dehydrogenase
mitochondria or tubular aggregate (sarcoplasmic reticulum)
aci phosphatase reaction
lysosome (in macrophage for inflam, deposit in acid maltase deficiency)
esterase stain
motor endplate
mutations centronuclear myopathy
DNM2 dynamin 2 aut dom Border Collie
BIN1 aut rec > dom Great Dane
TTN titin aut rec
MTM1 myotubularin X linked Labrador
PTPLA aut rec Labrador
abnomalies in endocytosis
