Classification of Muscle Disorders

Stephanie J. Valberg

A muscle disorder is usually suspected in large animals because of (1) increased, decreased, or abnormal muscle tone; (2) focal or generalized muscle damage (rhabdomyolysis); (3) muscle atrophy; or (4) exercise intolerance not associated with respira­tory, cardiovascular, or skeletal causes.

Altered Muscle Tone

Increased muscle tone may be neural in origin. For example, tetanus and strychnine poisoning increase muscle tone as a result of suppressed inhibition of upper motor neurons by interneurons. Increased motor neuron firing also occurs during seizures, with electrolyte imbalances, and with equine ear tick infestation. Visual, tactile, or auditory stimuli often precipitate painful sustained motor unit activity. Other probable neural disorders that intermittently increase muscle tone include periodic spasticity and spastic paresis in cattle, stiff horse syndrome, and “shivers” in draft and warmblood horses. Focal nerve root irritation may also result in focal muscle twitching.

Increased muscle tone can also arise from myopathic dis­orders. Persistently enhanced muscle tone may occur because of muscle contractures, which are characterized by fixation of myofilaments in a persistently shortened position without neural input.²² Contractures are usually extremely painful and associ­ated with rhabdomyolysis. Contractures occur with malignant hyperthermia and some forms of exertional myopathy. Intermit­tent, abnormal muscle contractions without rhabdomyolysis occur when sarcolemmal ion channels within the muscle cell membrane are dysfunctional.²³,²⁴ Caprine myotonia congenita and equine hyperkalemic periodic paralysis are examples of diseases caused by sarcolemmal ion channel dysfunction.

Moderate weakness in horses may be caused by central spinal cord disorders. More profound weakness may arise from neuropathies affecting motor neurons (equine motor neuron disease [EMND], hypocalcemia), decreased neural input at motor end plates (botulism), marked muscle atrophy (EMND) or rhabdomyolysis of postural muscles, or severe electrolyte imbalances (hypokalemia).

Muscle Atrophy

Atrophy is defined as a reduction in muscle size, specifically a reduction in muscle fiber diameter or cross-sectional area. Atrophy may occur in response to a variety of stimuli. Denerva­tion removes the normal low-level tonic neural stimulus that is necessary to maintain muscle fiber mass. Complete denerva­tion of a muscle results in more than a 50% loss of muscle mass within a 2- to 3-week period.^16,25 A good example of this is “Sweeney” in horses, in which the suprascapular nerve is damaged and muscles over the scapula atrophy. Other denervat­ing conditions such as EMND show a slower and more general­ized progression of gross muscle atrophy. Electromyographic abnormalities following denervation are apparent within 5 days, and it may take 3 weeks for maximal changes to develop. Increased insertional activity, positive sharp waves, and bizarre high-frequency discharges and fibrillation potentials are seen in denervated muscle.¹² Pyknotic nuclear clumps and small angular slow-twitch type I and fast-twitch type II fibers with concave sides are characteristic of neurogenic atrophy in muscle biopsies. In some cases, hypertrophy of remaining motor units may occur in neurogenic atrophy, and renervation is indicated by target fibers and fiber type grouping.

Muscle atrophy may also be caused by disuse, malnutrition, cachexia, corticosteroid excess, and immune-mediated myositis. Skeletal muscle is a plastic tissue, with approximately 1% to 5% of the contractile mass undergoing remodeling on a daily basis. If a negative nitrogen balance occurs, net protein withdrawal from the skeletal muscle mass begins within 48 to 72 hours. This type of atrophy is distinguished from neurogenic atrophy by a slower progression of atrophy, normal electro­myographic findings, and muscle biopsies that are characterized by primarily atrophy of type II muscle fibers.

Muscle Necrosis

Muscle necrosis (rhabdomyolysis) as evidenced by elevations in serum CK, LDH, and AST can be focal or generalized. Many infectious, toxic, nutritional, ischemic, and idiopathic factors result in muscle fiber necrosis. When attempting to identify an etiology, it is helpful to characterize rhabdomyolysis in horses as associated with exercise or not. Specific causes of exertional and nonexertional rhabdomyolysis are listed in Boxes 42.1 to 42.3.

Necrosis represents injury to organelles within a muscle fiber or within a segment of that fiber. Many myopathies associated with generalized rhabdomyolysis interrupt normal muscle metabolism, and cell death results from an inability to maintain homeostasis within the myofiber. Although a variety of external or internal insults may cause rhabdomyolysis, they often share a final common pathway leading to cell death.²⁷ Under normal conditions, considerable energy is expended by muscle cells to pump the calcium that accumulates in the sarcoplasm during contraction into the sarcoplasmic reticulum. If cell membrane function is disrupted or if the energy pathways that generate adenosine triphosphate for the calcium pump are impaired, excessive calcium may accumulate in the sarco­plasm. Although some calcium can be sequestered by the mitochondria, eventually mitochondria become overloaded and oxidative metabolism ceases; oxygen free radicals are generated; phospholipases are activated, inducing the arachi­donic cascade; calcium-dependent proteases are stimulated; and complement is activated.

Muscle ischemia occurs commonly with acute trauma, the compartment syndrome in recumbent animals, downer syn­drome, and vascular occlusion. Compartment syndrome often involves the triceps muscle or extensors of the hindlimb because

■ BOX 42.1

■ BOX 42.2

Classification of Nonexertional Myopathies in Horses

Classification of Exertional Myopathies in Horses

1. Infectious

• Viral

• Sarcocystis fayeri

• Anaplasma phagocytophilum

• Streptococcus equi

• Clostridium spp.

• Abscesses

2. Immune mediated

• Infarctive purpura hemorrhagica

• Immune-mediated myositis

3. Nutritional myopathies

• Nutritional myodegeneration

• Selenium deficiency, vitamin E deficiency

• Vitamin E-deficient myopathy

4. Toxic myopathies

• Feed contaminants

• Ionophores

• Plant toxins

• Trematones

• Hypoglycin A

5. Traumatic or anesthetic

• Focal muscle strain

• Fibrotic myopathy

• Postanesthetic myopathy

6. Muscle cramping

• Electrolyte disturbances

• Hypocalcemia

• Synchronous diaphragmatic flutter

• Ear ticks

• Shivers

7. Myotonia

• Myotonia congenita

• Myotonia dystrophica

• Hyperkalemic periodic paralysis

8.

• Glycogen branching enzyme deficiency

• Polysaccharide storage myopathy type 1

• Polysaccharide storage myopathy type 2

• Malignant hyperthermia

1. Focal muscle strain

2. Sporadic exertional rhabdomyolysis

• Dietary imbalances:

• Vitamin E, selenium, electrolytes

• Exercise in excess of training

• Exhaustion

3. Chronic exertional rhabdomyolysis

• Polysaccharide storage myopathy type 1

• Polysaccharide storage myopathy type 2

• Malignant hyperthermia

• Recurrent exertional rhabdomyolysis

• Idiopathic exertional rhabdomyolysis

■ BOX 42.3

Classification of Myopathies in Food Animals

1. Infectious

• Clostridium

• Sarcocystis

2. Nutritional

• Selenium, vitamin E

• Hypokalemia

3. Toxic

• Feed additives

• Ionophores

• Plants

• Gossypol, Cassia, white snakeroot

• Chemical

4. Traumatic

• Muscle crush syndrome

5. Genetic

• Caprine myotonia

• Bovine pseudomyotonia

• Porcine malignant hyperthermia

• Bovine and ovine myophosphorylase deficiency

• Porcine RN(-) glycogen storage disease

they are often compressed in down animals or during anesthesia. Hypotension during surgery contributes to the development of this syndrome. Acute muscle infarction may occur with purpura hemorrhagica or disseminated intravascular coagulation, and on postmortem examination characteristic well-demarcated areas of hemorrhagic necrosis are evident. Muscle areas in contact with the ground in recumbent animals are most sus­ceptible to infarctions in animals with vasculitis. Clinically, acute infarctions are an extremely painful condition that may resemble colic. Chronic occlusive diseases, such as iliac thrombosis, often allow collateral circulation to develop, thereby avoiding acute signs of ischemia at rest. Although muscle has an impressive ability to regenerate, if a disease process is severe enough to disrupt the basement membrane, muscle may be replaced by connective tissue and fat. This occurs most fre­quently after trauma, such as following tearing of the semi­membranosus or tendinosus in horses (fibrotic myopathy), and with severe infarctions.