Myopathy should be considered in patients with obvious difficulties in walking or with an abnormal gait but normal paw positioning reactions (conscious proprioception). In contrast, in patients with gait disturbances caused by a spinal cord lesion (paresis), paw positioning reaction is usually lost before paresis develops. Other signs of generalized muscular diseases include: exercise intolerance, weakness (often exercise induced), bunny hopping gait, muscle atrophy or hypertrophy, stiff/stilted, short-strided gait, ventroflexion of the neck (more common in cats), megaesophagus and difficulties in prehending/swallowing food, whereas the paw positioning reaction, segmental spinal reflexes, and cranial nerve test are usually normal in pure myopathies. Sometimes, those clinical symptoms can only be induced by exercise, whereas the relaxed patient might be completely normal. Exercise tests should be used to monitor body temperature since some myopathies are characterized by excessive heat production (i.e., exercise-induced collapse). Changes of body temperature, however, should be compared to temperature changes in healthy patients after performing the same exercise as the diseased patient.

In cases of suspected muscular diseases the following diagnostic tests should be considered:

 Blood chemistry: creatine kinase (CK), aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH), potassium, calcium, magnesium, sodium, glucose, cholesterol

 Complete blood count

 Chest radiographs (check for megaesophagus, thymoma)

 Tensilon test (injection of the ultra-short-acting acetylcholine esterase inhibitor edrophonium hydrochloride)

 Urine analysis (incl. amino acid screening to check for abnormal concentration of certain metabolites)

 Electrodiagnostics (electromyography, nerve conduction studies)

 Muscle biopsies

 Additional tests:

 Lactate/pyruvate before and after exercise to diagnose mitochondrial myopathies (samples have to be stored in special containers: check with your laboratory before taking blood samples)

 2M-antibody titer - anti-AChR antibody titer for myasthenia gravis

 Serology/PCR for infectious agents - genetic tests for primary myopathies (exercise-induced collapse in Labrador retrievers, central core-like myopathy, myotonia congenita, malignant hyperthermia syndrome, Magyar Vizsla myositis or myopathies secondary to storage diseases

 Tests for endocrinopathies - carnitine concentration in muscle, plasma and urine - plasma cholinesterase activity

 Cardiac troponin I

One or more muscle enzymes (CK, ASAT; LDH) may be elevated. However, normal muscle enzymes do not rule out myopathic disease.

The Tensilon test may help to establish a clinical diagnosis of acquired myasthenia gravis, though measuring acetylcholine receptor antibodies is considered the gold standard. Short-term blocking of acetylcholine degradation using the esterase inhibitor edrophonium allows more acetylcholine to be available resulting in partial or complete resolution of clinical symptoms for a few minutes. A strong positive response is very suggestive of myasthenia gravis, whereas a mild response might be seen with many neuromuscular diseases.

Electromyography often reveals spontaneous muscle activity in anesthetized patients, when healthy muscle should be electrically silent. The pattern of spontaneous electrical activity (positive sharp waves, fibrillation potentials, myotonic discharges, pseudomyotonic discharges) may be indicative of a certain type of muscular pathology; they are, however, rarely pathognomonic for a specific etiology. In addition, spontaneous muscle activity may be caused by primary muscle pathology as well as by muscle pathology secondary to denervation. Therefore, if electromyography reveals spontaneous activity, nerve conduction studies should be performed as well in order to differentiate between myopathy and neuropathy.

If primary myopathy is suspected based on the results of electrodiagnostic tests, muscle biopsies should be taken and analyzed. However, myopathies are often part of a more generalized neuromuscular disease involving muscles as well as peripheral nerves. Therefore, combined muscle and nerve biopsies should be considered, since the diagnostic yield may be increased by analyzing both tissues simultaneously. The decision on which muscle is biopsied should be based on the following considerations: muscle pathology is often more severe in more proximal appendicular muscles, take biopsies from muscles with more severe changes on electromyography, do not biopsy fibrotic muscles with end-stage disease, biopsy muscles for which there is previous interpretive experience (i.e., cranial tibial muscles, triceps muscle, biceps muscles, vastus lateralis muscle, temporal muscle), harvest muscles from a site remote to tendinous insertions and aponeurosis, do not biopsy muscles where electromyography has been performed before, since needle insertion may cause artificial muscle lesions, biopsy muscle with low expected morbidity. The nerve chosen for biopsy does ideally innervate the biopsied muscle facilitating interpretation of muscles and/or nerve pathology. Muscle biopsies obtained by an open approach are superior to those retrieved by any percutaneous sampling method. The major disadvantage of the latter is the limitation in sampling size. Whenever possible, one should aim for samples of one cubic centimeter in size.

The most information is obtained from fresh frozen muscle specimen. Therefore, muscle samples should be collected in isopentane precooled in liquid nitrogen and shipped on dry ice. Alternatively, muscle and nerve tissue is stored in a saline-dampened gauze sponge in a small container shipped under refrigeration using an overnight service to a laboratory specialized in evaluation of nerve and muscle specimen.

Do not store muscle specimen in formalin since analysis of paraffin-embedded samples is of limited value only. However, check with your laboratory which type of storing and shipping is most appropriate to them. In adequately collected, processed and shipped muscle samples, regular hematoxylin-eosin staining as well as staining for fiber-type distribution, enzyme activities and detection of storage products can be performed.

Histopathological examination rarely results in a definite diagnosis of a specific disease (i.e., dystrophin deficiency, storage disease, central core myopathy); more commonly the identified pathology is assigned to a certain type of diseases (i.e., inflammatory, toxic-metabolic, degenerative) with an additional list of most likely differentials. In that case, further tests are often necessary.

The following diseases might be considered if primary myopathy is suspected:

 Inflammatory: infectious:

 Bacterial (clostridia, Leptospira), protozoal (Toxoplasma, Neospora), rickettsial (Ehrlichia)

 Viral immune-mediated: necrotizing polymyositis, dermatomyositis, masticatory myositis

 Neoplastic/paraneoplastic: lymphoma, rhabdomyosarcoma, paraneoplastic polymyositis

 Non-inflammatory:

 Immune-mediated: myasthenia gravis

 Metabolic/toxic: hypothyroidism (dog), hyperthyroidism (cat), hypoadrenocorticism (dog), hyperadrenocorticism, mitochondrial myopathies, storage diseases, electrolyte imbalances (i.e., hypokalemia), hypoglycemia, organophosphate/carbamate intoxication

 Nutritional: vitamin E deficiency

 Vascular: ischemic myopathy

 Unclassified: exercise-induced collapse, myotonia, central-core myopathy, Labrador myopathy, exertional rhabdomyolysis, muscular dystrophy, feline hypertrophic muscular dystrophy

Therapy has to be based on a specific diagnosis. However, in cases, where a diagnosis could not be established despite appropriate diagnostic tests, an unspecific treatment using nutritional supplements can be tried: L-carnitine (50 mg/kg PO BID) and coenzyme Q10 (100 mg/dog/day PO).

Additional information on clinical signs, diagnostic tests and therapy of myopathies can be found in:

1.  Shelton GD. Neuromuscular diseases. Vet Clin North Am Small Anim Pract. 2002 (January).

2.  Shelton GD. Neuromuscular diseases II. Vet Clin North Am Small Anim Pract. 2004 (November).

3.  Shelton GD. Routine and specialized laboratory testing for the diagnosis of neuromuscular diseases in dogs and cats. Vet Clin Pathol. 2010 (September).