Treatment of Myopathies and Neuropathies

Chapter 240

Treatment of Myopathies and Neuropathies

Neuromuscular diseases can be difficult diagnostic challenges with only a limited number of available therapeutic options. However, the most common diseases affecting muscle and peripheral nerve are treatable if a correct diagnosis is reached before irreversible pathologic changes occur. For other neuromuscular diseases, particularly the inherited myopathies and neuropathies, no therapeutic options currently are available. The old dictum “To help, or at least to do no harm” (Hippocrates) is particularly true for this group of diseases. Beginning a trial of corticosteroid treatment before performing at least the minimum necessary diagnostic tests can delay or impair the ability to reach a correct diagnosis, delay initiation of specific therapies, and possibly result in irreversible contractures or even death of the animal. Further, glucocorticoid treatment results in a polydipsic and polyphagic animal with an increased susceptibility to infection.

The first important step is to achieve accurate neuroanatomic localization. Neuromuscular diseases are disorders of the motor unit and as such affect neuronal cell bodies in the ventral gray matter (ventral horn) of the spinal cord (motor neuron disease), peripheral nerve (neuropathies), neuromuscular junction (disorders of neuromuscular transmission), and muscle (myopathies). A careful neurologic examination is critical. If the wrong anatomic localization is made, an incorrect diagnostic pathway will be chosen and valuable time wasted. An incorrect diagnosis can lead to inappropriate treatments that may result in severe debilitation or be life threatening.

Once clinical signs have been localized to the neuromuscular system, specific laboratory testing should be performed to reach an accurate diagnosis. Testing to collect a minimum data set for neuromuscular diseases should include a complete blood cell count, serum chemistry profile including creatine kinase (CK) activity and electrolyte concentrations, thyroid screen, urinalysis, and, in most cases, acetylcholine receptor antibody titer to test for myasthenia gravis. Electrodiagnostic testing, including electromyography and measurement of sensory and motor nerve conduction velocity, provides important information regarding the distribution and nature of the disorder but requires specialized equipment and expertise. Cerebrospinal fluid analysis may be beneficial in disorders of nerve roots such as acute polyradiculoneuritis and protozoal diseases. A definitive diagnosis ultimately requires histopathologic evaluation of appropriately collected and processed muscle and peripheral nerve biopsy specimens. Although a specific diagnosis may not be reached in all cases, information regarding the underlying pathologic process can guide empiric therapy.

Treatment of the most common inflammatory myopathies (masticatory muscle myositis, polymyositis, infectious myositis) and noninflammatory myopathies (endocrine and exogenous corticosteroid induced), the less common noninflammatory myopathies (inherited myopathies), and the neuropathies are described in this chapter. Specific treatments for the various clinical forms of myasthenia gravis are covered in Chapter 239.

Treatment of Inflammatory Myopathies

The inflammatory myopathies, including the immune-mediated forms (masticatory muscle myositis, polymyositis, extraocular myositis, and dermatomyositis) and those associated with infectious diseases (particularly infections with the protozoal organisms Toxoplasma gondii, Neospora caninum, and Hepatozoon americanum) are relatively common in dogs. Myositis associated with neoplasia as a paraneoplastic or preneoplastic process occurs less commonly. Inflammatory myopathies occur rarely in cats as a paraneoplastic syndrome (thymoma) or associated with feline immunodeficiency virus (FIV) or feline leukemia virus (FeLV) infection. In my experience, purely immune-mediated inflammatory myopathies are uncommon in cats. Following a histologic diagnosis of an inflammatory myopathy, infectious diseases should be ruled out by serologic testing, and screening for neoplasia should be initiated. If results are negative, an immune-mediated cause is likely.

Masticatory Muscle Myositis

Masticatory muscle myositis (MMM) is the most common inflammatory myopathy occurring in dogs and occurs in rare cases in cats. In MMM clinical signs are restricted to the muscles of mastication without involvement of the limb muscles or other muscle groups. MMM has been recognized in most breeds of dogs and can begin as early as 3 months of age. Although MMM is a bilateral disease, clinical signs can appear unilateral, with one side affected more markedly than the other. A particularly severe, breed-associated form of MMM has been identified recently in young cavalier King Charles spaniels. In the acute form of MMM, pain and swelling of the masticatory muscles and trismus are common clinical findings. Typically the jaws cannot be opened, even under anesthesia. The cause of this inability to the open the jaw in the acute stage has not been identified, and fibrosis is not obvious in muscle biopsy specimens. In the chronic stage there is atrophy of the masticatory muscles with or without jaw pain or immobility. In end-stage MMM, atrophy is severe, and the jaw may not open more than a couple of centimeters. In muscle biopsy specimens in end-stage disease, there is severe loss of muscle mass and replacement with fibrous tissue. MMM is very responsive to corticosteroid therapy in the acute stages and moderately so in the chronic stages. Once end-stage MMM is present, typically there is only minimal, if any, response to corticosteroids.

Because of the propensity for fibrosis, an early and accurate diagnosis is critical to achieve a positive clinical outcome. The serum CK activity usually is normal or only mildly elevated. Although a serologic assay currently is available for the diagnosis of MMM (through demonstration of antibodies to type IIM fibers by either immunohistochemical analysis or enzyme-linked immunosorbent assay), a biopsy of the temporalis muscle also is recommended to determine severity of the disease and long-term prognosis. Previous receipt of corticosteroid therapy at immunosuppressive dosages for longer than 7 to 10 days can lower antibody titers and produce negative results. In addition, animals with chronic, end-stage MMM can test negative for antibodies against type IIM fibers because most fibers of this type have been destroyed, which removes the antigenic stimulus. If a biopsy specimen is collected, care must be taken to ensure that the correct muscle is sampled. A common mistake is to biopsy the frontalis and not the temporalis muscle. The frontalis muscle lies directly under the skin and is not part of the masticatory muscle group. A biopsy specimen from the frontalis muscle will not be diagnostic. Instructions for collection of an appropriate temporalis muscle biopsy specimen are given in a 2004 review of MMM by Melmed and colleagues (2004).

Following confirmation of the diagnosis of MMM, immunosuppressive therapy with prednisone should be initiated at 1 to 2 mg/kg q12h PO. Treatment should be continued until the level of CK activity (if elevated) has returned to the reference range, jaw mobility has returned to normal, and clinically evident jaw pain has resolved. Prednisone dosage then should be gradually decreased to the lowest alternate-day dose that keeps the dog free of clinical signs and continued for a period of at least 4 to 6 months. Relapses are common if treatment is stopped too soon. The most frequent causes of a poor clinical outcome are a delay in initiating appropriate treatment, inappropriate dosages of corticosteroids, and treatment for too short a period of time. If prednisone is poorly tolerated, other immunosuppressive drugs such as azathioprine may be added to reduce the glucocorticoid dosages. There are no controlled clinical trials examining the efficacy of any therapeutic regimens in the treatment of canine inflammatory myopathies; thus recommendations for the use of other agents, including cyclosporine, mycophenolate mofetil, and intravenous immunoglobulin, cannot be given.

In end-stage MMM, fibrosis may be severe, and the jaw may open only a few centimeters, if that. In these cases resolution of clinical signs with corticosteroid therapy should not be expected. Maintenance of hydration and adequate nutrition may be problematic, and dogs may have generalized muscle wasting from malnourishment related to the lack of food intake. Under no circumstances should the jaw be opened forcibly, even under sedation or anesthesia, because a jaw fracture may result. Surgical procedures such as mandibular symphysiotomy or partial mandibulectomy or hemimandibulectomy may allow tongue movement for lapping food and water. These procedures are best performed by a surgical specialist. The position of the tongue should be noted under anesthesia to avoid inadvertent protrusion and swelling from venous congestion.


Polymyositis (PM) is an immune-mediated inflammatory myopathy that can affect all muscle groups, including the masticatory muscles, the limb muscles, and the esophageal, pharyngeal, and laryngeal muscles. PM can occur alone or as part of a generalized autoimmune disorder such as systemic lupus erythematosus. The serum CK activity may be normal or mildly to moderately elevated, depending on the degree of muscle damage and the distribution of cellular infiltrates. The IIM antibody titer yields negative results in most cases, even with clinical involvement of the masticatory muscles. Clinical signs may include a stiff, stilted gait; muscle atrophy; variable myalgia; regurgitation and dysphagia; and contractures in chronic PM.

The diagnosis of PM is confirmed by muscle biopsy findings. Biopsy specimens should be collected from more than one muscle since cellular infiltrates can have a patchy distribution and may be missed on individual biopsy specimens. The large proximal limb muscles such as the vastus lateralis or biceps femoris of the pelvic limb and the triceps muscle of the thoracic limb are suggested as biopsy sites. Once a diagnosis of an inflammatory disorder has been histologically confirmed and infectious agents have been ruled out, immunosuppressive therapy should be initiated as for MMM. The serum CK activity should be monitored, and the animal should be observed for resolution of clinical signs. Because cardiac muscle also may be involved, testing for cardiac troponin I is warranted. Periodic screening for an underlying neoplasia also is suggested, particularly in the boxer breed. Breed-associated PM has been described in vizsla and Newfoundland dogs.

Extraocular Muscle Myositis

A focal, presumed immune-mediated inflammatory myopathy, extraocular myositis, selectively affects the extraocular muscles while sparing the masticatory and limb muscles. The clinical presentation is that of a bilateral exophthalmos in the acute stage or a restrictive strabismus in the chronic stage. The serum CK concentration is normal, and results of IIM antibody testing are negative. A presumptive diagnosis of extraocular myositis can be made by clinical presentation, a negative result on the IIM antibody test, and demonstration of swollen extraocular muscles by orbital ultrasonography or magnetic resonance imaging. In the acute stage resolution of clinical signs with immunosuppressive dosages of corticosteroids can be rapid. In chronic stages of extraocular myositis with fibrosis of the extraocular muscles, a favorable response to immunosuppression should not be expected. Restrictive strabismus may result when treatment is inappropriate or delayed.

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Treatment of Myopathies and Neuropathies
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