Neuromuscular Disorders

Karen Kline, DVM

Neuromuscular disorders are diseases that affect the neuromuscular components: the nerve root, the peripheral nerve, the neuromuscular junction and the muscle. Causes of these disease are multiple and can be classified according to the DAMNIT scheme of disease etiology (degenerative, anomalous, metabolism, neoplastic, nutritional, infectious/inflammatory, immune-mediated, traumatic, toxin). Diagnostics for these disorders depend on the signalment, history, physical and neurologic exams and include routine and advanced bloodwork, endocrine testing titers, electrodiagnostics such as electromyography and surgical biopsies of muscle and/or nerve . This lecture will focus on the 4 components of the neuromuscular system and their disorders.

Neuropathies involve lesions in the peripheral nerve (axon, myelin sheath). They are common in domestic animals with the canine being the most commonly represented. A large percentage are congenital or hereditary and are poorly understood pathophysiologically. Clinical signs of neuropathies are caused by dysfunction of structures innervated by the motor nerve and sensory fibers. The lower motor neuron (LMN) is the final common pathway between the CNS and target organs and can be somatic (skeletal muscle) or autonomic (smooth muscle). Clinical signs of LMN dysfunction include: flaccid muscles, weakness, paralysis, muscle atrophy, hypo or areflexia, and +/- sensory loss. Pathologic changes in the nerve can include axonal degeneration, demyelination, cell body disease, axon disease and, most commonly, Wallerian degeneration.

Congenital/hereditary disorders include canine giant axonal neuropathy, Boxer neuropathy, hypertrophic Neuropathy of Tibetan Mastiffs, Canine sensory neuropathies, and canine laryngeal paralysis (hereditary/acquired forms). Most of these diseases are degenerative in nature and may not be treatable.

Inflammatory/Immune-mediated neuropathies include polyradiculoneuritis or "Coonhound paralysis". This disease has been recognized in hunting dogs who are exposed to raccoon saliva, but also has been seen in dogs with no exposure to racoons. The disease is similar to human acute polyneuritis (Guillain-Barre syndrome). The cause is an acute, multifocal immune-mediated demyelination and degeneration of the axon. There is a possible link to racoon saliva, but has not been proven. The disease attacks primarily the ventral roots and spinal nerves. Neurologic signs develop in some dogs 7 to 14 days post-exposure and early clinical signs can include pelvic spreading to front limb paresis that progresses to tetraplegia and hyporeflexia. After 3 to 5 days diffuse neurogenic muscle occurs. The cranial nerve, sacral and caudal nerve roots are all generally spared, so the patient can urinate, defecate and retain normal mentation and CNN function. Few reports of respiratory paralysis have been seen. Interestingly, most dogs are still able to wag their tails, but most have a voice change. Diagnostics include an accurate history, assessment of vaccination status, routine bloodwork and/or electrodiagnostics (if concern over other LMN diseases). Rabies should always be included as a differential if vaccination status is questionable. Treatment is supportive and includes excellent nursing care, physical therapy, and avoidance of decubital ulcers. Improvement can take 4-8 weeks and the prognosis is generally good to excellent for recovery.

Metabolic diseases that affect the peripheral nerve include diabetes mellitus (DM), especially in the feline, and hypothyroidism. DM is theorized to slow axonal transport due to hyperglycemia effects. Hypothyroidism has been theorized to lead to axonal degeneration and demyelination due to low levels of T4 (thyroxine). Clinical signs are associated with either neuropathic and/or myopathic changes. Diagnostics and treatment are aimed at finding the underlying cause.

Idiopathic causes of neuropathies include distal denervating disease, distal polyneuropathy in the canine, idiopathic CNN VII neuropathy, (most common in the Cocker Spaniel), idiopathic "old dog" vestibular disease and trigeminal neuritis. The underlying cause of these diseases are unknown and may be linked to an infectious, immune-mediated or degenerative etiology. Trauma is the most common cause of neuropathies in domestic animals (mechanical blow, gunshot, fracture, pressure, iatrogenic). Neurotmesis implies complete severance of all nerve structures. Axon temesis involves damage to nerve fibers resulting in axonal degeneration, but regeneration can occur since the nerve sheath is intact. Neuropraxia involves mild contusion or pressure, to the nerve, but no structural damage. Brachial plexus neuropathy involves avulsion/compression of the ventral nerve roots and/or dorsal (sensory) roots. Clinical signs consist of LMN signs to the affected limb (areflexia, hypotonia, neurogenic muscle atrophy and plegia. Diagnosis is made through history, and at times electrodiagnostics. Prognosis is variable, depending upon the extent of the injury.

Other neuropathies include paraneoplastic myoneuropathy that can occur secondary to neoplasia. Pathogenesis is theorized to be linked to paraneoplastic effects on the muscle or nerve tissue (immune-mediated, degenerative or inflammatory in nature). Diagnosis and treatment is based on finding the underlying cause. Prognosis is guarded and the neurologic signs may remain after treatment. Ischemic myoneuropathy has been described in both the cat and dogs and is linked with thromboembolism which can occur secondary to any condition that predisposes the patient to a thromboembolic state. Examples include hypertrophic cardiomyopathy in the feline, Cushings disease, immune-mediated disease, or glomerular disease in either species. Diagnosis, treatment and prognosis is based upon determining and treating the underlying disease.

Myopathies are diseases that affect the muscle and follow the DAMNIT scheme in terms of etiology. Congenital and hereditary myopathies include myotonic myopathy and the newly recognized syndromes of metabolic myopathies of which hereditary Labrador Retriever myopathy is a subcategory. These diseases are associated with in born defects in muscle oxidative metabolism and , in some cases, mitochondrial dysfunction. Diagnosis is based upon findings on electrodiagnostics and muscle biopsy as well as findings on special immunostaining of muscle and electron microscopy. Treatment is based upon the underlying cause and consists mainly of dietary supplementation and exercise modification. Another category of myopathies are those of immune-mediated origin. Masticatory myositis is an immune-mediated disorder that affects the Type 2M muscle fibers of the muscles of mastication in the canine. Only these muscles are selectively affected. Clinical signs include pain on opening the mouth, temporal and masseter, muscle atrophy, and in chronic cases, inability to open the mouth (trismus) due to fibrosis. Diagnosis is made by history and the presence of Type 2M antibodies in the serum. Treatment is composed of immunosuppressive doses of corticosteroids that are tapered over weeks. The prognosis is generally guarded to good for recovery if diagnosed early. Another category of immune-mediated muscle disease is polymyositis, which is an inflammatory disease of the muscle that has been associated with systemic lupus erythematosus. Signs are consistent with neuromuscular dysfunction and diagnosis is through muscle biopsy (lymphocytic infiltration of muscle fibers). Treatment is with tapering doses of corticosteroids over weeks to months. One must be careful to establish a definitive diagnosis on muscle biopsy to rule out other infectious causes of myoneuropathy such as Toxoplasma gondii and Neospora caninum.

Junctionopathies involve abnormal neurotransmission of ACh (acetylchloine) at the neuromuscular junction. These disorders include botulism, tick paralysis, myasthenia gravis and aminoglycoside intoxication. All mimic diffuse peripheral neuropathies (LMN signs, and or hyporeflexia) except for myasthenia gravis which mimics a peripheral myopathy (episodic weakness). Botulism is diagnosed through a history of carrion ingestion and the findings of LMN signs and a CNN VII neuropathy. Treatment is supportive. Tick paralysis is diagnosed by response to tick removal. Acquired myasthenia gravis is diagnosed by history and a positive ACh receptor antibody titer in the serum. Treatment is with long acting ACh esterase inhibitors (ie pyridostigmine bromide, Mestinon^�) and immunosuppressives such as azothiaprine, (Imuran^�).

Diagnosis and treatment of neuromuscular disorders can be challenging and, at times, frustrating. Accurate owner history and neurologic evaluation is essential for early diagnosis and management.