Introduction

This expansive group of disorders includes diseases of peripheral nerve, skeletal muscle, and the neuromuscular junction (NMJ). In general, neuropathies are characterized by poor reflex activity and decreased muscle tone. Patients with myopathies often have evidence of weakness (often exercise-related), normal reflexes and sensory function (e.g., proprioception, nociception), muscle atrophy, and myalgia. Neuromuscular junction disorders are often typified by generalized weakness with normal sensory function. As a group, the diagnostic tests directed at arriving at a diagnosis are similar, regardless of the specific disease. A complete discussion of all the PNS disorders is beyond the scope of this presentation. Several selected neuropathies and myopathies will be discussed, in addition to a discussion of acquired myasthenia gravis (MG).

Selected Neuropathies

Paraneoplastic Neuropathy

These neuropathies are believed to develop as an indirect, rather than a primary effect of the underlying neoplasia. The pathogenesis of this phenomenon is unknown, but several hypotheses exist. Potential explanations include elaboration of some neurotoxic factor by the tumor, disruption of axonal and/or Schwann cell metabolism by the tumor, and an immunologic reaction to antigens shared by the neoplasm and peripheral nerve elements (i.e., innocent bystander reaction). A paraneoplastic polyneuropathy has been reported occasionally with pancreatic insulinomas, and the potential exists for the associated hypoglycemia to be responsible for the neuropathy. However, peripheral nerves are particularly resistant to the effects of hypoglycemia and peripheral neuropathy has not been associated with any other disease that results in hypoglycemia. The hypoglycemia is probably not a major contributing factor to the neuropathy. Clinical signs are variable and may range from a subclinical neuropathy to severe LMN tetraplegia. The existence of this phenomenon makes it imperative to rule out the existence of neoplasia in animals presenting with neuropathies, especially older patients. Diagnosis of an insulinoma is usually based upon an abnormal amended serum insulin/glucose ratio, and sometimes identifying the pancreatic tumor via ultrasound or exploratory laparotomy. Treatment is directed toward the underlying neoplasia. There is no specific treatment for the associated neuropathy. The prognosis for recovery from paraneoplastic neuropathies (assuming adequate control of the primary tumor) in dogs and cats is presently unknown. In people with paraneoplastic neuropathies, the prognosis is often poor for recovery. Prognosis for control of the underlying neoplasia depends largely upon tumor type and location.

Acute Idiopathic Polyradiculoneuritis (Coonhound Paralysis)

An idiopathic inflammatory disorder primarily involving both axons and myelin of ventral nerve roots occurs in dogs, and is probably one of the most common polyneuropathies in this species. Although much less common, an analogous polyneuropathy has been described in cats. Varying degrees of axonal and myelin loss in motor nerves explain the characteristic clinical signs. There is evidence that axonal loss is more prominent than demyelination in most dogs with polyradiculoneuritis. Demyelination is thought to be most severe in the ventral nerve roots in dogs, with minimal myelin loss in the major nerve trunks. Although the pathogenesis is uncertain, an autoimmune process is suspected. The term coonhound paralysis refers to those dogs with a history of being bitten or scratched by a raccoon shortly before developing clinical signs of disease. The term idiopathic polyradiculoneuritis refers to patients with an identical clinical disorder, but with no possible exposure to raccoons. These two subcategories probably reflect the same disease syndrome, with the trigger for the inflammatory process being as yet unidentified in the latter subcategory. The typical clinical scenario for acute idiopathic polyradiculoneuritis describes a rapidly developing LMN paresis/plegia, usually beginning in the pelvic limbs, and eventually involving the thoracic limbs. Most affected animals will progress to being either non-ambulatory tetraparetic or tetraplegic within 10 days of initial onset of clinical signs. It is not uncommon for this stage of dysfunction to be reached within a 72 hour period of time. Development of life-threatening respiratory paralysis is a concern, especially in the more rapidly developing cases. Loss of voice (dysphonia, aphonia) is common and some patients will also exhibit facial weakness. Spinal reflexes are typically absent (with the exception of the perineal reflex, which is normal), muscles are hypotonic, and neurogenic atrophy develops quickly in recumbent patients. Proprioceptive placing reactions will be normal in those animals that still have enough motor ability to perform the efferent limb of these tests. These patients retain the ability to urinate and defecate, and will readily eat and drink if the head is supported. Pain sensation also remains intact. In fact, these animals often seem hyperesthetic upon limb manipulation, which may reflect the inflammatory nature of the disease.

In dogs with coonhound paralysis, there is a history of an encounter with a raccoon approximately 1–2 weeks prior to the onset of clinical signs. In patients with idiopathic polyradiculoneuritis, identical clinical features are present as described, with no possibility of a raccoon scratch or bite. Many, if not most of these dogs will exhibit abnormal EMG activity with normal motor nerve conduction velocities (MCV). The patients often do not have enough functional axons to ambulate, but the remaining axons have essentially normal myelination. CSF examination may demonstrate increased protein levels. There is no specific therapy for this disease. Glucocorticoids have been suggested, but there is no evidence of efficacy. Nursing care, physical therapy, and proper nutrition are essential for recovery. The inflammatory phase of this disorder is believed to be transitory, but the damaged axons need to remyelinate and, to some degree, regrow.

The prognosis for full recovery is often favorable, but it is typically prolonged, usually taking several weeks to several months. Some patients develop life-threatening respiratory paresis/paralysis in the acute phase of the disease (usually those dogs whose signs progress rapidly over 72 hours) and may need to be mechanically ventilated. Re-exposure to raccoons is to be avoided in dogs having recovered from coonhound paralysis, as this may trigger a relapse of disease symptoms.

Selected Myopathies

Autoimmune Polymyositis

This is an autoimmune inflammatory disease of unknown pathogenesis primarily affecting the appendicular muscles. It is more commonly reported in dogs than cats. While any age or breed dog can be affected, most are middle-aged large breed dogs of either sex. Young Boxers and Newfoundlands may be predisposed, and this may be a pre-neoplastic disorder in the former breed. Clinical signs may be acute or chronic and may include generalized weakness that is often worsened by exercise, hyperesthesia upon muscle palpation (myalgia), regurgitation (due to megaesophagus), dysphagia, depression, fever, muscle swelling acutely, muscle atrophy chronically, shifting leg lameness, and voice change. Diagnosis is based upon typical clinical findings, as well as results of various diagnostic tests. CK levels may be elevated, EMG examination typically reveals abnormalities, and muscle biopsy reveals myofiber necrosis, phagocytosis, and regeneration, with a nonsuppurative inflammatory infiltrate. Immunoglobulin localization to the sarcolemma may also be demonstrable immunohistochemically. Treatment consists of oral prednisone therapy at immunosuppressive doses (e.g., 1–2 mg/kg, q 12 hours) until clinical remission is achieved, with subsequent tapering of the dose. The prognosis is generally favorable, although relapses may occur.

Masticatory Myositis

This is an autoimmune disorder in which antibodies are directed against the muscles of mastication (e.g., temporalis, masseter, pterygoid muscles). The pathogenesis of this disease is uncertain, but the distinct myosin isoform and myofiber type (Type II M) of masticatory muscles may explain why they are preferentially targeted by the immune response Dogs of numerous breeds (usually large breeds) and both sexes have been reported with this disorder, but the German Shepherd dog seems to particularly predisposed. Most dogs with masticatory myositis are young adults. Cats are rarely reported with this disorder. Clinical signs typically include painful swelling of the masticatory muscles and varying degrees of trismus. The clinical signs are often acute in onset and may be recurrent. Exophthalmos and fever are also occasionally observed. Palpation of the masticatory muscles and attempts to force the jaws open often elicit a painful response. Diagnosis of this disorder is based on clinical features and demonstration of antibody directed against Type II M myofibers in serum. CK levels may also be elevated and EMG examination often reveals abnormalities. Muscle biopsies may reveal varying degrees of inflammatory infiltrates, and myofiber necrosis and phagocytosis. Treatment is immunosuppressive doses of prednisone (1–2 mg/kg per os, q 12 hours) for 3–4 weeks, after which the dosage is tapered to every other day. Tapering is slowly continued in order to achieve the lowest every other day dosage that will control clinical signs. Most dogs will show a favorable response to therapy, but relapses are common. In some cases, prednisone can be replaced by azathioprine as the maintenance immunosuppressant drug, relieving some or all of the side effects associated with glucocorticoid therapy. In general, the prognosis for this disease is favorable.

Acquired Myasthenia Gravis

Acquired myasthenia gravis (MG) is an autoimmune disorder in which autoantibodies directed against nicotinic ACh receptors of skeletal muscle are produced, resulting in muscle weakness. Focal, generalized, and acute fulminating forms of MG have been described in dogs and cats. Focal MG is characterized by the lack of obvious appendicular (limb) muscle weakness, Generalized MG patients exhibit obvious appendicular weakness. Acute fulminating MG is a rapidly progressing form of the disorder that is often fatal. Definitive diagnosis of MG is typically made via a positive serum test for circulating autoantibodies directed against the nicotinic ACh receptor. Treatment consists of anticholinesterase agents, often combined with immunosuppressive therapy. Prognosis is guarded, generally being more favorable in cases in which megaesophagus is absent or corrected with therapy.