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Clinical and Genetic Traits of Hereditary Canine Myopathies
ACVIM 2003
Dr. Stephane Blot, DVM, PhD, DECVN
Ecole Veterinaire d'Alfort, France

INTRODUCTION

For the past 15 years, tremendous work has been done in the clinical identification of several inherited myopathies, but a lot of work remains to be done in the knowledge of the lethal gene and in the understanding of the pathogenesis. This presentation will review various inherited myopathies with a special focus on the autosomal recessive transmitted form of a Labrador retriever myopathy.

GENERAL CLINICAL PRESENTATION

The typical sign is locomotor weakness. It is usually worsen after exercise or disappears with exercise (myotonia). Weakness may be discrete with a stiff gait, tremors, an abnormal posture such as neck ventroflexion, palmigradic or plantigradic stance, splaying digits, bunny hopping gait, or a difficulty in negotiating simple motions. Weakness may also be extreme mimicking a neurogenic disease (tetraplegia). Muscle atrophy is bilaterally symmetric, however hypertrophy can occurred in some territories. In most cases, hypotony with preserved tendon reflexes is encountered. Hypertonic muscles are observed in myotonia. Absent tendon reflexes are sometimes encountered in congenital myopathies or later in the course of degenerative myopathies. Muscular fibrosis and contracture inducing reduced range of articular movement is frequent. Several other striated muscles such as masticatory, extra-ocular, cardiac, digestive or respiratory musculature may display in conjunction to skeletal striated muscles or alone clinical deficits. A myopathy should be suspected in front of regurgitation, vomiting, dysphagia, dysphonia, or ophtalmoplegia. Weakness is a non specific sign thus the diagnostic requires the use of specialized ancillary tools (electromyography, biochemical analyses, muscle biopsy). A classification can be done upon the knowledge of the gene, its product or the transmission pattern (table 1).

MUSCULAR DYSTROPHIES

Muscular dystrophies are a heterogeneous group of inherited myopathies clinically defined by a progressive muscular weakness and wasting, elevated creatine kinases level, and histologically characterized by chronic degeneration and regeneration of muscle fibers with fibrosis and replacement of myofibers by adipocytes. More than 20 forms of muscular dystrophy are known in human beings; most likely many of theses also occur in dogs and remain to be discovered.

X-linked muscular dystrophy

X-linked muscular dystrophy results from alteration of a huge dystrophin gene which is carried by the X chromosome. The absence of dystrophin or the production of a deficient dystrophin at the sarcolemme leads to degeneration of the muscle fibers.

The dystrophin deficiency is the most common muscular dystrophy (1, 2). It was first confirmed in the Golden Retriever (mutation in the intron 6). Since then, the disease has been detected in the Rottweiler (exon 5, German short haired pointer (large deletion), and the Labrador retriever (intron 20). It was suspected in the Samoyed, the Groenendaeler Shepherd, the Irish Terrier, the Brittany Spaniel, the Rat Terrier, the Pembroke Welsh Corgi, the Miniature Schnauzer and the Japanese Spitz dog. The first clinical signs appears early at 8 weeks and are manifested by stiff gait and reduced opening of the mouth. Within few weeks, exercise intolerance and muscle atrophy appear. Hypertrophy of the tongue and of the diaphragm can lead to severe digestive signs. Posture is modified: abduction of the elbows, adduction of the hocks, palmigradic and plantigradic stance and lordosis. Signs stabilize towards 6 months and movement becomes restricted with onset of contractures. Death may occur within the first few days, or the animal may well survive for several years but die because of difficulty in eating or from bronchopneumonia (50% of death at 15 months of age). A dilated cardiomyopathy occurs later, leading to death ultimately. CK level is markedly elevated (10,000-100,000 U/L), but varies with time. Electromyography reveals high frequency and pseudomyotonic discharges.

Muscle biopsy discloses necrosis, fibrosis, regeneration and sites of intracellular calcification. Fiber size varies with numerous centralized nuclei. Dystrophin is absent on immunohistochemistry and on western blots. Prednisolone (0.5 mg/kg/d) may improve the demeanor of the affected dogs. Breeders are advised not to breed the mother because of its very likely carrier status.

Non X-linked muscular dystrophies

Several case reports of canine muscular dystrophies without dystrophin deficiency are reported in the literature. Clinical phenotype is nearly similar to dystrophin deficiency. The molecular deficiency and the transmission pattern were rarely characterized, thus no breeding program can be advised.

LABRADOR RETRIEVER MYOPATHY

The autosomal recessive Labrador Retriever myopathy, reported in United States, Australia, Great Britain, Switzerland and France, has been initially described as a dystrophic disease affecting type 2 muscles fibers, however, the search for involvement of dystrophin or of proteins involved in muscular dystrophy has remained fruitless (1).

Clinical signs appear within 8 weeks to 11 months of age, the peak being around 3 months. General weakness with muscle atrophy, low head carriage and a bunny hopping gait are mainly noted. Fatigability may be time-variable with acute but short crisis of paraplegia. The animal exhibits a very slender profile contrasting with the muscular stature of a healthy Labrador. Noteworthy, whatever the age, tendon reflexes are absent or reduced. Occasionally, there is kyphosis or megaoesophagus. Clinical signs stabilize after 8 months of age, except the acute crisis that vanishes within few days, the disease is not lethal by itself but death induced by bronchopneumonia can occur in adult affected dogs.

CK level is almost normal. Electromyography reveals early fibrillation potentials, slow positive waves and repetitive complex discharges, with varied frequencies amongst muscles. Muscle biopsy shows a marked variation of muscle fiber diameter, with small-sized angular or round-shaped fibers and large fibers with centralized nuclei. Subsequently, most fibers display centrally placed nuclei, the sarcoplasmic architecture is disorganized and in proximal appendicular muscles, the muscle fiber slow type is highly and precociously predominant. Endomysial fibrosis spreads slightly out, adipocytes replace some fiber and necrosis is visible on rare occasion.

In our French colony, we localized the disease on canine chromosome 2 (CFA02); the gene and its product are under investigation. The availability of genetic markers allows breeders to eliminate asymptomatic carriers from breeding (3).

MYOTONIA AND PERIODIC PARALYSES

Myotonia congenita

Myotonia is characterized by prolonged muscle contraction in response to mechanical, electrical, or voluntary contraction. The mechanism of non dystrophic myotonia is related to dysfunction of one or several ionic sarcolemma channels (chloride channel for myotonia, calcium channel for periodic paralysis and sodium channel for both). In Chow-Chow and in Miniature Schnauzer, myotonia appears to be inherited through an autosomal recessive mode (4).

Clinical signs are visible soon after the pup became ambulatory. Immediately after rest, the gait is stiff and animals may frequently fall forwards with the forelimbs spread out. Affected dogs have difficulty in rising from sternal recumbency; a stridorous breathing and regurgitations are described. There is an enlargement of proximal limb and axial musculature. Progressive muscle rigidity regresses significantly as exercise is prolonged, but is worsen by cold (except in the miniature Schnauzer). A gradual deterioration may appear, or affected dogs seem to stabilize after a few months. But because of the premature nature of clinical myotonia, bone or articular deformations may appear. Noteworthy, mandibular shortening and distoclusion is frequent in affected Miniature Schnauzers.

A myotonic dimple persists several seconds after percussion of the surface of a muscle. The CK level is normal or only moderately increased (below 600 U/L). Electromyography records high frequency discharges that wax and wane, these are called myotonic discharges. True myotonic discharges should be distinguished from complex repetitive discharges. Muscle biopsy displays mild abnormalities such as increased variability in diameter, hypertrophic fibers, and increased centralized nuclei.

There is no satisfactory therapy; antagonists to voltage gated sodium channel (procainamide, mexiletine) seem the most effective to decrease the clinical myotonia.

A molecular screening test is now available to readily identify Miniature Schnauzer carriers (www.vet.upenn.edu/penngen) and to eliminate them from breeding. In a study of 300 asymptomatic dogs, 20% were heterozygotes (4).

Periodic paralysis

Hyperkalemic periodic paralysis is characterized by episodes of flaccid paralysis associated with increased serum potassium. A disease analogous has been reported in a dog (4).

Myotonic dystrophy

Myotonic dystrophy is an inherited multisystemic disease where a muscular dystrophy occurs with clinical myotonia and myotonic discharges. Canine Myotonic dystrophy was suspected in two isolated case reports (4).

METABOLIC MYOPATHY (5)

Glycogenosis

Glycogenosis are uncommon storage diseases due to an inborn enzymatic deficiency in the glycolytic metabolism, and lead to the accumulation of glycogen-like material in cells. Signs are non-specific. Muscular weakness, syncope, rhabdomyolysis, and occasional convulsions caused by hypoglycemia after a period of fasting or moderate exercise are clinical hallmarks. Amongst the seven types discovered in human beings, only three types have currently been identified in dogs.

Type II glycogenosis is caused by a deficiency in alpha-glucosidase (acid maltase). This fatal disease is described in Lapland dogs with an autosomal recessive trait. The clinical signs, dysphagia, frequent vomiting and polypnea, appear towards the age of 6 months. The animals die in their second year.

Type III glycogenosis is caused by a deficiency in amylo-1.6-glucosidase. Described in German shepherd and Akita dogs, clinical signs appear during the second month and the disease is rapidly fatal.

Type VII glycogenosis is caused by a phosphofructokinase deficiency and has been identified in English Springer Spaniels and in Cocker Spaniels. The animals show intermittent exercise intolerance and suffer from muscle cramp and hemolytic anemia at approximately 8 months of age. Death may occur after acute hemolysis in the course of a hyperventilation phase. It is inherited as an autosomal recessive trait (6, 7) and a molecular test is available (www.vet.upenn.edu/penngen) to identify carriers.

Mitochondrial myopathies

Mitochondrial myopathies are complex diseases defined by a functional abnormality (an enzymatic deficiency) or a structural abnormality of the mitochondria (membrane transporter deficiency). A pyruvate dehydrogenase deficiency has been identified in the Clumber Spaniel and in the Sussex Spaniel. In these dogs, exercise leads to collapse and severe metabolic acidosis (1).

Table 1. Example of inherited myopathies and transmission patterns

Disease
Mode of inheritance
Gene location
Gene product
Breed

Muscular dystrophies

X-linked
XR
ChrX

distinct mutations
dystrophin
Golden retriever, Rottweiler,

German short haired pointer,

Labrador retriever...

Non X-linked
AR

AR or AD
ND

ND
Laminin alpha2

ND
Mix breed dog

Rottweiler...

Labrador retriever myopathy
AR
Chr2
ND
Labrador retriever

Myotonia congenita
AR
Chr14*
ClC-1 (chloride channel)
Miniature Schnauzer (Chow-Chow)

Hyperkaliemic periodic paralysis
ND
ND
Sodium channel?
American Pit Bull Terrier

Myotonic dystrophy
ND
ND
ND
Boxer dog, Rhodesian Ridgeback

Malignant hyperthermia
AD
Chr01
RYR1 (ryanodine receptor)
Mixed breed

Metabolic myopathies

Glycogen storage disease

Type II
AR
ND
Acid maltase
Lapland dog

Type III
AR
ND
Amylo 1-6 glucosidase
German shepherd, Akita

Type VII
AR
Chr10*
M-type Phosphofructokinase
English Springer Spaniel, Cocker Spaniel (same mutation for both breeds)



Inheritance: XR: sex-linked recessive, AD: autosomal dominant, AR: autosomal recessive. ND: Not Determined.

Location: chromosomal assignment of the morbid locus, or of the gene when known, * result obtained from the syntenic maps between human and canine chromosomes.

CONCLUSIONS

Inherited myopathies in dogs are relatively uncommon and may be difficult to diagnose. They display non-specific signs and require specialized diagnostic tests. A correct diagnosis is important for the owner because the prognosis varies for the various diseases. It is all the more so since several inherited diseases can occur in the same breed. A definite diagnosis is also important as knowledge of the inheritance patterns and the availability of molecular tests are of significant relevance to breeders. So far, few canine diseases have been discovered in comparison to numerous ones in human beings. Therefore, it is important to be aware of the existence of additional muscular disorders.

REFERENCES

1. G. D. Shelton and E. Engvall. Muscular dystrophies and other inherited myopathies. Vet Clin North Am Small Anim Pract 32 (1):103-124, 2002.

2. S. Blot, N. Carelle, N. Deburgrave, C. Escriou, V. Chetboul, J.-C. Kaplan, and F. Leturcq. LRMD: a new canine model of dystrophinopathy in a Labrador Retriever strain. J Neurol Sci 199:S9, 2002.

3. L. Tiret, S. Blot, J. L. Kessler, H. Gaillot, and J. J. Panthier. Genetic mapping of the canine centronuclear myopathy (cCNM). J Neurol Sci 199:S11, 2002.

4. C. H. Vite. Myotonia and disorders of altered muscle cell membrane excitability. Vet Clin North Am Small Anim Pract 32 (1):169-87, vii, 2002.

5. S. R. Platt. Neuromuscular complications in endocrine and metabolic disorders. Vet Clin North Am Small Anim Pract 32 (1):125-146, 2002.

6. U. Giger, M. P. Reilly, T. Asakura, C. J. Baldwin, and J. W. Harvey. Autosomal recessive inherited phosphofructokinase deficiency in English springer spaniel dogs. Anim Genet 17:15-23, 1986.

7. U. Giger, B. F. Smith, C. B. Woods, D. F. Patterson, and H. Stedman. Inherited phosphofructokinase deficiency in an American Cocker Spaniel. J Am Vet Med Assoc 201:1569-1571, 1992.

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)
Stephane Blot, DVM, Ph.D, DECVN
Ecole Veterinaire d'Alfort
7, av du General de Gaulle
Maisons-Alfort Cedex F-94700
FRANCE

Funded by AFM; Employed by ENVA

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AUTRE TEXTE, plus général
Canine and Feline Myopathies
Western Veterinary Conference 2002
Paul A. Cuddon Veterinary Specialists of Northern Colorado
Loveland, Colorado, USA

Objectives

To understand the gamut of different etiologies for muscle disease in the dog and cat.

To know which breeds of dogs have an inherited predisposition for certain myopathies.

To know which diagnostic tests are valuable to reach a diagnosis of lipid myopathy, immune-mediated muscle disease, and metabolic/endocrine associated myopathy.

To know the options for treatment and the prognosis for the various myopathies seen in the dog and cat.

Key Points

Myopathies in small animals are divided into inherited/suspected inherited myopathies and acquired myopathies.

Numerous breeds are predisposed to inherited myopathies, including the Chow Chow and miniature Schnauzer (myotonia); Golden Retriever and Irish Terrier (X-linked muscular dystrophy); and Collies and Shelties (dermatomyositis).

Acquired myopathies can be either functional or structural. Functional myopathies include the mitochondrial myopathies while the structural myopathies include immune-mediated disease and those secondary to metabolic or endocrine diseases.

Immune-mediated myopathies are subdivided into localized and generalized myositis.

Masticatory myositis represents a focal myositis secondary to immune attack against the Type 2M myofibers that are unique to the muscles of mastication. This disease can present as either acute, swelling of the muscles with accompanying pain, or chronic, progressive atrophy. Definitive diagnosis is made via serum anti-type 2M myofiber antibody assay.

Polymyositis can be either associated with other immune disease or neoplasia, or a breed associated immune disease in Newfoundlands.

Muscle biopsy is the diagnosis of choice in dogs with polymyositis.

Immune-mediated myopathies are best treated with immunosuppression via p0rednisone and azathioprine. Cyclophosphamide may be used in refractory cases.

Myopathies are commonly associated with metabolic and endocrine disease. Cats develop a polymyopathy secondary to a total body depletion of potassium. Dogs can develop a myopathy secondary to hypothyroidism and Cushing’s disease.

Treatment of the primary metabolic/endocrine dysfunction will improve or reverse the myopathic signs.

Overview

Myopathies in small animals consist of both inherited or suspected inherited myopathies and those that are related to metabolic/endocrine disease, infectious disease or immune mediated dysfunction.

Hereditary or Suspected Hereditary Myopathies

1. Hereditary Myotonia Of Chow Chows - autosomal recessive trait

2. Myotonia of Miniature Schnauzers, Great Danes, Cocker Spaniels, and Staffordshire terriers

3. Autosomal Recessive Myopathy With Type 1 Predominance In Labrador Retrievers

4. Muscular Dystrophy Of Golden Retrievers and Irish terriers - an X-linked defect in the dystrophin gene - identical to Duchenne muscular dystrophy

5. Canine Familial Dermatomyositis - Collies and Shelties - inherited disease with variable expressivity

Canine Lipid Storage Myopathies

Etiology and Pathogenesis

Abnormal amounts of lipid accumulate in muscle with the lipid accumulation being the predominant pathologic alteration

Most are associated with a derangement of carnitine metabolism (either primary or secondary), with mitochondrial abnormalities, or with disorders of fatty acid oxidation involving ß-oxidation

Clinical Findings

Acute or chronic poorly localizable muscle pain

Muscle atrophy

Weakness

Stiffness

Lameness

Exercise intolerance

Muscle tremors

+/- Cardiomyopathy

Seen in any aged dog with no sex predilection, although majorityare adults

Diagnosis

Electrophysiology - EMG and CMAP amplitudes

Muscle biopsy - accumulation of lipid droplets within myofibers in fresh- frozen muscle biopsies (oil red-O stain)

Evaluation of lactate (pre and post-exercise) and pyruvate levels in plasma and urine

Carnitine quantitation (total, free, and esterified) in muscle, plasma, and urine

Quantitative urine organic acid analysis - differentiates pathologic causes of lactic acidemia

Treatment

If low levels of muscle carnitine (primary) - oral L-carnitine at 50 mg/kg BID. Response is not as good in animals where the decrease in muscle carnitine is secondary to significant lactic and pyruvic aciduria

Coenzyme Q10–1 mg/kg PO daily

Riboflavin - 50–100 mg PO daily

Vitamin C - 50 mg/kg PO daily

Dietary manipulation - low fat, high carbohydrate, high protein diet with supplementation with medium-chain triglycerides

Acquired Myopathies

Inflammatory Myopathies (Myositis)

Protozoal Myositis

Etiology and pathogenesis

Toxoplasma gondii or Neospora caninum.

Neospora caninum is now thought to be the major cause of a radiculoneuritis and polymyositis occurring typically in young pups between 2 and 4 months of age.

Infection in most instances is thought to extend from the dam via the placenta.

Clinical findings

Different syndromes of the disease may be seen.

Cases with severe polyradiculoneuritis and polymyositis often have progressive rigid paraplegia with the limbs being difficult or impossible to flex even under anesthesia.

Pelvic limb reflexes cannot be elicited, although pain sensation often is retained.

The muscles are often firm on palpation and may be atrophied.

In such cases, the thoracic limbs appear clinically normal.

Other dogs have signs predominantly of polymyositis, with generalized weakness that worsens on exercise.

Diagnosis

Often increased serum CK level

May be an eosinophilia.

Serum titers to N. caninum have been positive; titers to T. gondii usually negative.

EMG studies.

Muscle biopsies confirm the presence of necrotizing polymyositis, although protozoal cysts may be difficult to find.

Immune Myositis of Masticatory Muscles

Etiology and pathogenesis

This is an autoimmune disorder directed against the Type 2M myofibers peculiar to the dorsal group of masticatory muscles innervated by the mandibular nerve.

These have different origins in embryological development.

There are circulating antibodies to Type 2M masticatory muscle fiber proteins which do not cross react with limb muscle fibers.

There is a necrotizing myositis, with regenerative changes and infiltrates of predominantly mononuclear cells.

In the more chronic forms, connective tissue is markedly increased.

Clinical findings

The clinical presentation can be divided into acute and chronic forms, although intermediate stages also are seen.

In the acute disease:

There is swelling of the muscles, sometimes sufficient to produce exophthalmos and pain on opening the mouth.

The masticatory muscles may feel edematous.

Tonsils and submaxillary lymph nodes may be enlarged.

Pyrexia can be present and the dog may show a degree of malaise.

There often is a neutrophilia and in some instances eosinophilia.

Mild anemia and raised globulin levels also may be present.

The chronic disease:

May follow an acute episode or develop insidiously.

Major features - atrophy of masticatory muscles and limitation of jaw opening.

Atrophy is usually, though not invariably, bilateral.

On muscle biopsy, there is multifocal inflammation, fiber necrosis and an increase in connective tissue, particularly perimysial. Muscle biopsy reveals inflammatory cell infiltrates.

Diagnosis

Suspected on clinical grounds and confirmed by biopsy.

Eosinophils are not a distinctive feature.

On electromyography, there is an increase in insertion and spontaneous activity (in severely fibrotic muscles, there is no activity).

In acute disease, CK is usually increased, although this may not be the case in chronic disease.

Serum anti-type 2M myofiber antibody assay.

Differential Diagnosis

Should be distinguished from neurogenic atrophy following mandibular nerve damage.

Treatment

In both the acute and chronic diseases, glucocorticoids (Prednisolone 1–2 mg/kg orally bid for 4 weeks, then reduce to 1/2 mg/kg orally bid for 1 month then decrease dosage further) are indicated to suppress the inflammation, reduce connective tissue formation and suppress the autoimmune response.

Treatment with immuno-suppressive doses should be continued for at least a month, even though the acute signs may have resolved.

The disease often recurs, so repeated or continuous therapy may be necessary.

It is unlikely that atrophy in chronic cases will improve much.

May lead to an inability to open the jaw.

Polymyositis

Etiology and Pathogenesis

Polymyositis is a poorly understood, suspected autoimmune myopathy.

Although this syndrome can occur at any age in dogs, almost all documented cases have been in adult animals with a reported predilection for large breeds and with a higher incidence in females.

These findings are similar to reports in people, where polymyositis is uncommon in childhood and most adult cases occur in the fifth and sixth decades of life, again with a greater predilection for women.

A breed associated polymyositis, however, has recently been recognized in young Newfoundlands.

The immune reaction in polymyositis appears to be predominantly T cell-mediated. There is an oligoclonal expansion of autoaggressive T cells which show increased expression of activation molecules (CD25 and HLA-DR) and increased adhesion capacity.

The T cells in muscle biopsies from human polymyositis are mainly CD3+CD8+ and LFA-1+ cells. Endothelial cells and myofibers surrounded by T cells show an increased staining for ICAM-1.

It is thought that LFA-1/ICAM-1 interactions enable activated CD8+ T cells to migrate selectively into the inflamed muscle and to adhere to MHC-class I-positive myofibers, the suspected principal target, leading to tissue injury.

The induction of MHC-class I antigens in muscle fibers precedes the inflammatory cell infiltration.

The specific sarcolemmal membrane antigen is unknown, although evidence points to it being an endogenous self-antigen rather than an endogenous viral antigen.

An association with systemic lupus erythrematosus (SLE) has been described.

Other cases with a probable immune-based arthritis/ polymyositis complex unassociated with SLE have been recognized.

A relationship between myositis and malignancy also has been suggested. An immune, paraneoplastic syndrome associated with thymoma may be seen.

Diagnosis

Presence of classic clinical signs (stiff-stilted gait, muscle atrophy, generalized muscle tremors, exercise-induced weakness, dysphagia, megaesophagus, and possible laryngeal paralysis).

Generalized spontaneous muscle activity on electrophysiology.

Variable increases in serum CK and AST.

Muscle biopsy.

Treatment

Immunosuppressive doses of prednisone (1–1.5 mg/kg orally twice daily.

Azathioprine at 2 mg/kg once daily initially then try to decrease to 2 mg/kg every other day.

Continue steroid immunosuppression until serum CK returns into normal range.

Metabolic Polymyopathy

Feline Hypokalemic Polymyopathy

Clinical signs

Affected cats have a sudden onset of generalized weakness, pronounced cervical ventroflexion and a reluctance to walk.

Clinical pathology

Decreased serum K+ (2.0–3.3 mEq/L)

Increased CK (up to 10,000 IU/L)

Increased serum creatinine and/or BUN and metabolic acidosis

These cats - usually have negative FeLV titers.

Other diagnostic tests

Generalized EMG abnormalities are usually detected although muscle biopsies are often normal on L.M.

Dietary potassium is often marginal (< 0–3%) and there is an increased renal potassium loss.

Pathophysiology

Decreased potassium produces initial muscle cell membrane hyperpolarization.

With continued K+ decrease - the membrane becomes more permeable to Na+ leading to hypopolarization and myopathic weakness.

A K+ - losing nephropathy has been postulated as the cause for the total body K+ depletion.

Treatment

K+ supplementation produces improvement with a gradual but complete resolution of the polymyopathy (oral and/or parenteral).

Endocrine Related Myopathy

Hypothyroidism

Subclinical to clinical myopathy in mature dogs proposed to be related to a disturbance in CHO metabolism

Preferential type II myofiber atrophy

Treatment of hypothyroidism with Levothyroxine reverses the signs

Cushing’s Disease

Degenerative myopathy secondary to xs glucocorticoids

Type II myofiber atrophy, subsarcolemmal masses, focal necrosis, fiber size variation, & fiber splitting

Stiff gait, muscle atrophy, pelvic limb rigidity, and pseudomyotonia (dimpling and EMG changes)

Treatment of the Cushing’s disease tends to improve signs although this is dependent on the severity and chronicity of the disease.

Summary

Myopathies in dogs and cats can be either inherited (muscular dystrophy and myotonia) or acquired (polymyositis, masticatory myositis, and endocrine/metabolic associated myopathy. Recognition that certain breeds are predisposed to myopathy will aid the clinician in diagnosing these diseases in young dogs. The lipid storage and metabolic myopathies will be discovered through functional testing of the dog (carnitine and lactate levels) in combination with muscle biopsy. Both the acute and chronic forms of masticatory myositis are easily recognized on physical examination and are definitively diagnosed via a serum antibody assay. Polymyositis presents with an array of clinical signs. It is best diagnosed by muscle biopsy analysis. A diagnosis of metabolic or endocrine myopathy is usually made with the recognition and positive diagnosis of the underlying metabolic or endocrine dysfunction. There is usually no specific treatment for the myopathy in these cases, but treatment of the underlying disease will commonly improve or reverse the muscle disease.

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)
Paul A. Cuddon,
Veterinary Specialists of Northern Colorado
Loveland, Colorado, USA

[CC & Ul]

EEEEEUUUUUUUUUUUUUUUUUUUHHHHHHHHHHHHHHHHH
EN FRANCAIS CADONNE QUOI ?????????????????????????

[bgmumu]

lol tu me l'enleve de la bouche CC & Ul

Je ne comprend pas l'anglais moi non plus
_________________

Parfois, c'est ça aussi l'amour: laisser partir ceux que l'on aime...

[dogalement]

excusez pour la langue,mais sur le site ou est l'article il n'y a pas le francais...
c'est pas évident a comprendre et malgré mes quelques bases...je suis pas tout.....
si quelqu'un peut traduire un peu ... c'est (tu l'avais compris Céline ...)
sur cette saloperie de maladie dont est atteind rescap.
merci aux éventuels traducteurs si ils peuvent éclairer ce dialecte......!
_________________
"le temps est le grand art de l'homme"
Napoléon 1er 1807

[gisounet]

Eh, les filles, sur votre souris, vous avez une fonction : translate page, et voila ce que ça donne

Voilà le texte:
Traits cliniques et génétiques de Myopathies canin héréditaire
ACVIM 2003
Dr. Stephane Blot, DVM, PhD, DECVN
D'Alfort d'Ecole Veterinaire, France

INTRODUCTION

Pendant les 15 dernières années, le travail énorme a été effectué dans l'identification clinique de plusieurs myopathies hérités, mais beaucoup de travail reste à effectuer dans la connaissance du gène mortel et dans la compréhension de la pathogénie. Cette présentation passera en revue de divers myopathies hérités avec un foyer spécial sur la forme transmise récessive autosomal d'un chien d'arrêt de Labrador myopathy.

PRÉSENTATION CLINIQUE GÉNÉRALE

Le signe typique est faiblesse locomotrice. Il est habituellement empirent après exercice ou disparaissent avec l'exercice (myotonia). La faiblesse peut être discrète avec une démarche raide, des tremblements, un maintien anormal tel que le ventroflexion de cou, la position palmigradic ou plantigradic, les chiffres d'évasement, la démarche de houblonnage de lapin, ou une difficulté en négociant des mouvements simples. La faiblesse peut également être extrémité imitant une maladie neurogène (tetraplegia). Le muscle atrophy est bilatéralement symétrique, toutefois le bidon d'hypertrophie s'est produit dans quelques territoires. Dans la plupart des cas, hypotony avec des réflexes préservés de tendon est produit. On observe des muscles hypertoniques dans le myotonia. Des réflexes absents de tendon sont parfois produits dans les myopathies congénitaux ou plus tard au cours des myopathies dégénératifs. La fibrose musculaire et la contracture induisant la gamme réduite du mouvement articulaire est fréquente. Plusieurs autres muscles striés tels que la musculature de masticatoire, supplémentaire-oculaire, cardiaque, digestive ou respiratoire peuvent montrer dans la conjonction aux muscles striés squelettiques ou aux seuls déficits cliniques. On devrait suspecter un myopathy devant le regurgitation, vomissant, dysphagia, dysphonia, ou ophtalmoplegia. La faiblesse est un signe non spécifique que le diagnostic exige ainsi l'utilisation des outils auxiliaires spécialisés (électromyographie, analyses biochimiques, biopsie de muscle). Une classification peut être faite sur la connaissance du gène, de son produit ou du modèle de transmission (tableau 1).

DYSTROPHIES MUSCULAIRE

Les dystrophies musculaires sont un groupe hétérogène de myopathies hérités médicalement définis par une faiblesse musculaire progressive et les kinases de gaspillage et élevées de créatine de niveau, et histologiquement caractérisé par la dégénération et la régénération chroniques des fibres de muscle avec la fibrose et le remplacement des myofibers par des adipocytes. Plus de 20 formes de dystrophie musculaire sont connues dans les êtres humains; très probablement plusieurs de thèses également se produisent chez les chiens et restent à découvrir.

dystrophie musculaire X-liée

la dystrophie musculaire X-liée résulte du changement d'un gène énorme de dystrophin qui est porté par le chromosome de X. L'absence du dystrophin ou de la production d'un dystrophin déficient au sarcolemme mène à la dégénération des fibres de muscle.

L'insuffisance de dystrophin est la dystrophie musculaire la plus commune (1, 2). On l'a confirmé la première fois dans le chien d'arrêt d'or (mutation dans l'intron 6). Depuis lors, la maladie a été détectée dans le Rottweiler (l'exon 5, short allemand haired l'indicateur (grande suppression), et le chien d'arrêt de Labrador (intron 20). On l'a suspecté dans le Samoyed, le berger de Groenendaeler, le Terrier irlandais, le Brittany Spaniel, le rat Terrier, le Pembroke Gallois Corgi, le Schnauzer miniature et le chien japonais de Spitz. Les premiers signes cliniques apparaît tôt à 8 semaines et est manifestés par démarche raide et ouverture réduite de la bouche. Dans peu de semaines, l'intolérance et le muscle d'exercice atrophy apparaissent. L'hypertrophie de la langue et du diaphragme peut mener aux signes digestifs graves. Le maintien est modifié: abduction des coudes, de l'invocation des hocks, de la position palmigradic et plantigradic et de la lordose. Les signes stabilisent vers 6 mois et le mouvement devient restreint avec le début des contractures. La mort peut se produire dans les jours premiers, ou l'animal peut jaillir survivent pendant plusieurs années mais meurent en raison de la difficulté en mangeant ou du bronchopneumonia (50% de la mort à 15 mois d'âge). Une cardiomyopathie dilatée se produit plus tard, menant à la mort finalement. Le niveau de CK est nettement élevé (10.000-100.000 U/l), mais change avec du temps. L'électromyographie indique des décharges à haute fréquence et pseudomyotonic.

La biopsie de muscle révèle la nécrose, la fibrose, la régénération et les emplacements de la calcification intracellulaire. La taille de fibre change avec de nombreux noyaux centralisés. Dystrophin est absent sur les taches immunohistochemistry et sur occidentales. Prednisolone (0,5 mg/kg/d) peut améliorer le demeanor des chiens affectés. Des sélectionneurs sont conseillés de ne pas multiplier la mère en raison de son statut très probable de porteur.

Dystrophies musculaires non X-liés

Plusieurs enferment des rapports des dystrophies musculaires canins sans insuffisance de dystrophin sont rapportés dans la littérature. Le phénotype clinique est presque semblable à l'insuffisance de dystrophin. L'insuffisance moléculaire et le modèle de transmission ont été rarement caractérisés, ainsi aucun programme de multiplication ne peut être conseillé.

CHIEN D'ARRÊT MYOPATHY DE LABRADOR

Le chien d'arrêt récessif autosomal de Labrador myopathy, rapporté aux Etats-Unis, Australie, Grande-Bretagne, Suisse et France, a été au commencement décrit car une maladie dystrophic affectant des fibres de muscles du type 2, cependant, la recherche de la participation du dystrophin ou des protéines impliquées dans la dystrophie musculaire a (1) stérile resté.

Les signes cliniques apparaissent dans 8 semaines aux 11 mois de l'âge, la crête étant autour 3 mois. La faiblesse générale avec le chariot principal atrophy et bas de muscle et une démarche de houblonnage de lapin sont principalement notées. Fatigability peut être temps-variable avec la crise aiguë mais courte du paraplegia. L'animal montre un profil très mince différant de la stature musculaire d'un Labrador sain. Remarquable, celui que l'âge, réflexes de tendon soient absent ou réduit. De temps en temps, il y a cyphose ou de megaoesophagus. Les signes cliniques stabilisent après 8 mois d'âge, à moins que la crise aiguë qui disparaît dans peu de jours, la maladie ne soit pas mortelle par elle-même mais la mort induite par bronchopneumonia peut se produire chez les chiens affectés par adulte.

Le niveau de CK est presque normal. L'électromyographie indique des potentiels tôt de fibrillation, positif lent ondule et des décharges réitérées de complexe, avec des fréquences diverses parmi des muscles. La biopsie de muscle montre une variation marquée de diamètre de fibre de muscle, avec les fibres angulaires ou rond-formées de petite taille et les grandes fibres avec les noyaux centralisés. Plus tard, la plupart des fibres montrent les noyaux centralement placés, l'architecture sarcoplasmique est désorganisée et dans des muscles appendiculaires proximaux, le type lent de fibre de muscle est fortement et precociously prédominant. La fibrose d'Endomysial étend légèrement, les adipocytes remplacent une certaine fibre et la nécrose est évidente à l'occasion rare.

Dans notre colonie française, nous avons localisé la maladie sur le chromosome canin 2 (CFA02); le gène et son produit sont à l'étude. La disponibilité des repères génétiques permet à des sélectionneurs d'éliminer les porteurs asymptomatiques de multiplier (3).

MYOTONIA ET PARALYSIES PÉRIODIQUES

Congenita de Myotonia

Myotonia est caractérisé par contraction prolongée de muscle en réponse à la contraction mécanique, électrique, ou volontaire. Le mécanisme du myotonia non dystrophic est lié au dysfonctionnement d'un ou plusieurs canaux ioniques de sarcolemme (canal de chlorure pour le myotonia, canal de calcium pour la paralysie périodique et canal de sodium pour tous les deux). Dans le chow-chow et dans Schnauzer miniature, le myotonia semble être hérité par un mode récessif autosomal (4).

Les signes cliniques sont évidents peu après que le chiot soit devenu ambulatoire. Juste après le repos, la démarche est raide et les animaux peuvent fréquemment tomber expédie avec les forelimbs étendus. Les chiens affectés ont la difficulté en se levant du recumbency de sternal; une respiration stridorous et des regurgitations sont décrits. Il y a un agrandissement de membre proximal et de musculature axiale. La rigidité progressive de muscle régresse de manière significative pendant que l'exercice est prolongé, mais est empirent par le froid (excepté dans le Schnauzer miniature). Une détérioration progressive peut apparaître, ou les chiens affectés semblent stabiliser après quelques mois. Mais en raison de la nature prématurée du myotonia clinique, l'os ou les déformations articulaires peut apparaître. Le rapetissement et le distoclusion remarquables et mandibulaires est fréquent dans Schnauzers miniature affecté.

Une fossette myotonic persiste plusieurs secondes après la percussion de la surface d'un muscle. Le niveau de CK est normal ou seulement modérément accru (en-dessous de 600 U/l). L'électromyographie enregistre les décharges à haute fréquence qui cirent et s'affaiblissent, ceux-ci s'appellent les décharges myotonic. Les véritables décharges myotonic devraient être distinguées des décharges réitérées complexes. La biopsie de muscle montre des anomalies douces telles que la variabilité accrue de diamètre, les fibres hypertrophiques, et les noyaux centralisés accrus.

Il n'y a aucune thérapie satisfaisante; les antagonistes au sodium à déchenchements périodiques par tension creusent des rigoles (procaïnamide, mexiletine) semblent les plus efficaces pour diminuer le myotonia clinique.

Un essai de criblage moléculaire est maintenant disponible pour identifier aisément les porteurs miniatures de Schnauzer (www.vet.upenn.edu/penngen) et pour les éliminer de la multiplication. Dans une étude de 300 chiens asymptomatiques, 20% étaient des heterozygotes (4).

Paralysie périodique

La paralysie périodique de Hyperkalemic est caractérisée par des épisodes de la paralysie flasque liés au potassium accru de sérum. Une maladie analogue a été rapportée chez un chien (4).

Dystrophie de Myotonic

La dystrophie de Myotonic est une maladie multisystemic héritée où une dystrophie musculaire se produit avec le myotonia clinique et les décharges myotonic. On a suspecté la dystrophie canine de Myotonic dans deux rapports d'isolement de cas (4).

MYOPATHY MÉTABOLIQUE (5)

Glycogenosis

Glycogenosis sont les maladies rares de stockage dues à une insuffisance enzymatique innée dans le métabolisme glytolytique, et mènent à l'accumulation de glycogène-comme le matériel en cellules. Les signes sont non spécifiques. La faiblesse musculaire, la syncope, le rhabdomyolysis, et les convulsions occasionnelles provoquées par hypoglycemia après une période du jeûne ou de l'exercice modéré sont les cachets cliniques. Parmi les sept types découverts dans les êtres humains, seulement trois types ont été actuellement identifiés chez les chiens.

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http://gisoucreations.free.fr/

[gisounet]

Ann, Rescap a t'il reçu des vaccins? J'ai lu des articles terribles, condamnant les vaccins. Pour les humains, la vaccination aurait déclenché des scléroses en plaques, pour ne parler que de ça.

Sur ce site, il y a des articles qui donnent le frisson:

http://www.angryvet.org/francais/03_articles/vaccinations.htm

dont voici un aperçu:

Les cocktails de vaccins

Les vaccins à valence multiple (cocktail) qui sont d'usage courant en médecine vétérinaire et qui peuvent contenir un mélange de cinq à sept et meme neuf vaccins différents sont très pratiques du point de vue commercial et ils réduisent le traumatisme associé à l'inoculation. Mais, du point de vue médical, ces vaccins ne sont pas sans inconvénients et ils soulèvent pour plusieurs raisons une vive controverse dans le milieu vétérinaire.

D'une part, ils ne permettent pas de vacciner avec discernement selon le cas particulier de l'animal et ils ne nécessitent aucune connaissance approfondie des maladies en question. L'animal est vacciné systématiquement meme contre des maladies qu'il est peu probable qu'il contracte41. D'autre part, ces vaccins seraient à l'origine d'un nombre indéterminé d'échecs vaccinatoires et de réactions post-vaccinales indésirables.

Dans des conditions naturelles, seuls un ou deux microbes à la fois peuvent menacer un individu, jamais cinq, six ou neuf à la fois. Bombardé par des doses excessives de corps étrangers différents et de façon répétée, submergé par cette invasion massive, le système immunitaire s'embrouille et se trouve incapable de réagir efficacement; la vaccination risque donc d'échouer.

Par ailleurs, le système immunitaire peut s'affoler et fabriquer par erreur des anticorps qui attaquent et détruisent des éléments vitaux de son propre corps, comme les globules rouges et les plaquettes (éléments du sang intervenant dans la coagulation42). Selon le Dr Jean Dodds, une vétérinaire américaine, ces réactions ont lieu peu de temps après la vaccination, en général dans les mois qui suivent, et se traduisent par des hémorragies internes très graves difficiles à arreter et bien souvent fatales (maladies hémolytiques auto-immunes, thrombocytopénie, etc.). La fréquence de ces réactions est inconnue, mais les chiens de race pure ayant un système immunitaire défectueux (rottweiler, doberman, épagneul, etc.) seraient particulièrement prédisposés43.

Enfin, la grande pluralité de ces vaccins et la concentration élevée d'antigènes3qu'ils contiennent seraient aussi en cause dans l'apparition des cancers de peau chez le chat44.

Autres réactions adverses

De nombreuses autres réactions adverses ont été observées tant chez le chien que chez le chat. En voici une liste succincte:

réactions d'hypersensibilité (allergie au vaccin, états anaphylactiques);
suppression du système immunitaire et déclenchement d'une maladie latente, comme la leucémie, la péritonite infectieuse, l'immunodéficience féline;
interférence avec les résultats de certains tests diagnostiques (ELISA) entraînant de faux résultats positifs;
susceptibilité accrue aux allergies, soit au pollen, à la nourriture ou meme à son propre corps (maladie auto-immune de la thyroïde, du rein, des globules rouges, des plaquettes, etc.);
aggravation de certaines affections existantes, comme le cancer, l'épilepsie, les allergies.
À ces réactions s'ajoute la possibilité que se développe une forme atténuée de la maladie (virulence résiduelle) ou que, en raison d'une contamination bactérienne ou virale du vaccin, diverses maladies infectieuses se manifestent (variante de la maladie de Creutzfeldt-Jakob, par exemple).

En outre, certaines maladies chroniques, aussi bien chez les animaux que chez les humains, seraient en partie reliées à la persistance, dans les cellules, du corps des virus et des protéines utilisés dans les vaccins. Ce phénomène expliquerait l'augmentation récente du nombre de maladies chroniques chez les humains et chez les animaux45
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http://gisoucreations.free.fr/

[dogalement]

oui,rescap est vacciné...........

surtout avec une pension........

je vaccine serieux !!!

affreux l'article.......

et dire que dans 10 ans les vaccins seront peut etre déconseillés........
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"le temps est le grand art de l'homme"
Napoléon 1er 1807