Diseases of the Peripheral Neuromuscular System

Chapter 72

George C. Farnbach


Peripheral neural or muscular disease can occasionally be confused with orthopaedic disease. While the distinguishing characteristics of these two categories of disease can usually be observed during the physical examination, diagnosis is not always a simple matter. The hallmark of neural and muscular diseases is disuse of the flaccid type: sore limbs are carried; denervated limbs are dragged. However, peripheral soft tissue disease is often incomplete, leading to weakness and ataxia that are sometimes difficult to distinguish from gait abnormalities due to pain from orthopaedic problems. It is the purpose of this chapter to discuss the major peripheral nerve, muscular, and neuromuscular diseases in the dog, many of which might be confused with orthopaedic disease.

Peripheral Neuropathies

Peripheral nerve disease may be categorized according to pathophysiological mechanism: inflammation, trauma, degeneration, or toxicosis. It may also be categorized according to anatomical site and functional loss: for example, generalized motor; generalized sensory; complete motor and sensory of right sciatic. Traumatic lesions are almost always focal and complete (e.g., sciatic injection neuropathy), although brachial root avulsions, which are not uncommon, are often focal and incomplete. The diagnosis and treatment of traumatic lesions are discussed fully in other chapters of this book and will not be described here.

Inflammatory neuropathies, including "coonhound paralysis"(2) and other acute and chronic forms,(11) are most often generalized and predominantly motor in type, but they may be localized(4) and they may be predominantly sensory* or mixed in their functional effects. The classic form of inflammatory neuropathy in the dog is a progressive weakness, which generally starts in the hindlegs, not associated with sensory or mental deficits. The onset may be insidious and progression slow, or signs may develop suddenly. The results of peripheral nerve testing are often variable. In severe cases, complete motor nerve block may occur, making motor nerve conduction velocity (MNCV) determination impossible. If the period from onset to examination is less than 5 to 7 days, no sign of denervation may be detectable on needle electromyography (EMG). These cases aside, the usual results of nerve testing and EMG are indicative of slowed MNCV and muscular denervation in the severely affected areas. The finding of normal MNCV, however, does not rule out inflammatory neuropathy, since the presence of only a few normal axons in a motor nerve can lead to normal MNCV.

*McGrath JT: Personal communication.

Additional tests that might be beneficial and that are often performed when inflammatory neuropathies are suspected include spinal fluid analysis and peripheral nerve biopsy. Unfortunately, the results of these tests are often inconclusive. Cummings and deLahunta(2) report an increased protein content in cerebrospinal fluid (CSF) in dogs with coonhound paralysis, while others(11) report normal protein levels. Nerve biopsies are often normal in the face of severe disease, presumably because the inflammation is either patchy in its distribution or located in the ventral roots and not in areas of the peripheral nerve from which biopsy specimens can be easily obtained.

Prognosis and treatment of inflammatory neuropathies (particularly the cases not associated with raccoon bites) also present problems for which there are no simple solutions. As in humans, the leading cause of death in patients with these diseases is pneumonia secondary to respiratory insufficiency. The debilitation produced by the disease can be long lasting as well as profound, and the level of support and nursing care required to maintain such animals may be Herculean. There is no hard rule about the duration of illness, but more rapid recoveries are more common in dogs in whom the onset of disease has been sudden. A logical mode of therapy would seem to include the use of immunosuppressive levels of corticosteroids, but such treatment may not be advisable because corticosteroids may hasten the advent of pulmonary complications.(11) My preference is to use high levels of corticosteroids for a brief period-2 to 3 days- and if they prove to be beneficial as judged by neurologic evaluation, they are continued as needed. If the trial corticosteroid regimen produces no improvement, the drugs are stopped, and the clinician is left with simply trying to maintain the animal until the disease reverses itself, if it does. Once recovery begins either with or without corticosteroids, most animals regain normal or near normal function. A few, however, may be left severely disabled. One dog in my experience has required long-term corticosteroid therapy, and signs recur if medication is stopped.

In addition to inflammatory neuropathies, degenerative or toxic neuropathies are seen occasionally in the canine population. (3) The neuropathies of the toxic variety are usually of a mixed functional loss (i.e., both motor and sensory), although the presenting signs are most often referable to the motor deficits. Typically, these animals manifest an insidious onset of signs with gradual progression. Signs include weakness, ataxia, and loss of muscle mass and tone. Peripheral nerve testing often demonstrates a marked slowing in either MNCV or sensory nerve conduction velocity (SNCV) or both. Needle EMG may or may not show abnormal resting activity. The observable electrophysiological abnormalities are most often more pronounced in the more peripheral areas, suggesting a "dying back" phenomenon.(1) Diagnosis is made on the basis of peripheral nerve biopsy results. The degenerative neuropathies appear to be untreatable. Treatment of toxic neuropathies depends upon identification of the toxin, where possible, and action appropriate to the nature of the toxin.

Diseases of the Neuromuscular Junction


Perhaps the most common disease of the neuromuscular junction in the dog is canine myasthenia gravis, which appears to be similar, at least in its pathophysiology, to the human form of the disease. While presentations may be variable, a history of exercise-dependent weakness is classic. Affected animals may, however, appear weak independent of exercise, or they may manifest periodic weakness. In fact, whenever weakness without obvious cause is encountered, myasthenia should be considered. In the dog, as in humans, the adult-onset form of this disease has been demonstrated to be associated with humoral antibodies antagonistic acetylcholine receptors located on the postsynaptic muscle.(7)

The diagnosis of myasthenia can be confirmed either pharmacologically or electrophysiologically. The pharmacologic test depends upon the animal's response to a short-acting acetylcholinesterase inhibitor. Marked improvement in strength in response to the slow intravenous injection of less than 2.2 mg/kg of edrophonium chloride is considered positive for a clinical diagnosis of myasthenia. Neuromuscular junction testing of myasthenic animals demonstrates a decremental response of 20% or more upon repetitive stimulation at rates less than 7 Hz. This decrement can be eliminated through the use of cholinesterase inhibitors. Treatment consists of oral dosage with long-acting anticholinesterases such as neostigmine bromide at a rate of 0.55 mg/kg three times daily. In the dog, this medication can usually be eliminated after less than 2 to 3 weeks. We have seen one dog in whom complete and permanent reversal of signs was achieved by the edrophonium test described above.


In certain areas of the United States and in other parts of the world, a common disease of the neuromuscular junction is that produced by a toxin present in the saliva of gravid ticks of many species. This disease, tick paralysis, is seen as an ascending paralysis of skeletal muscle produced by the inhibitory effects of the toxin on the presynaptic release of acetylcholine in the nerve terminal. According to Soulsby,(13) all but two of the varieties of ticks described are capable of producing the disease. Signs include weakness, which may be profound, without sensory deficit. The disease may be fatal, with death due to respiratory paralysis. In the United States, recovery from paralysis usually occurs within 1 to 3 days after removal of the ticks.(5)

Diseases of Muscle


The most frequently seen nontraumatic disease of muscle in the dog is polymyositis. This condition produces a variety of signs that may be either acute or insidious and chronic in nature. It also produces a spectrum of histopathologic changes in affected muscle. This variability has led to a variety of classifications for the signs produced by the disease process: atrophic myositis, eosinophilic myositis, and polymyositis among others. All of these classifications have in common an idiopathic immunologic attack on muscle tissue, and all appear to be responsive to corticosteroid therapy. It appears, therefore, more reasonable to stress their similarities than their differences, and the single classification of polymyositis is most appropriate.

As noted above, polymyositis produces a spectrum of presenting signs. Affected animals may manifest only certain aspects of the disease, and any animal showing lameness or painful muscles for which other causes are not obvious should be suspected of polymyositis. The most common sign and the most easily recognized is trismus (lockjaw), which persists even under anesthesia, but it is not invariably present. When trismus is present, it may be accompanied by either swelling or wasting of the masticatory musculature. Other signs that are often seen with or without trismus include stiff gait, stiff and painful neck, and generalized muscle tenderness. In some cases the muscles of the larynx and pharynx and the esophagus may also be involved.

Diagnostic confirmation can be achieved through results of serum creatine phosphokinase (CPK) determination, EMG studies, and muscle biopsy. In my experience, virtually all animals in whom the results of muscle biopsy were positive and in whom a response to corticosteroid therapy was seen manifested remarkably elevated serum CPK levels,(6) although other investigators report far less correlation.(8) EMG studies generally reveal fibrillation potentials, positive sharp waves, and sometimes bizarre high-frequency activity in affected areas of muscle, although if the muscle damage is sufficiently severe, electrical silence may prevail. Histopathology of biopsy material, when positive, may reveal any phase or combination of acute and chronic inflammatory destruction of muscle. Eosinophils may or may not be seen in the biopsy material, and their presence or absence in the peripheral circulation, while interesting, is probably inconsequential. If the biopsy results are positive for inflammatory muscle disease, the diagnosis of polymyositis should be regarded as definitive; if the biopsy results are normal or equivocal and the EMG is abnormal and serum CPK elevated, a tentative diagnosis of polymyositis can be made and therapy instituted.

Therapy for polymyositis is most appropriately approached as a control program using adjusted doses of glucocorticoids. Even when long-term trismus has been present, the use of corticosteroids is adequate to restore function. However, if the disease process has affected the muscles of deglutition, functional restoration may not be complete and the threat of inhalation pneumonia may persist. The initial dose of corticosteroid should be in the immunosuppressive range (e.g., prednisone, 1 mg-2 mg/kg/day) until the active process is brought under control as judged by return to normal of serum CPK levels. Subsequently, the dose may have halved at appropriate intervals while improvement or stability is monitored. Roughly half of the cases of canine polymyositis require some low level of maintenance corticosteroid to prevent recurrence of the disease. Other dogs may not require maintenance doses but are always subject to recurrence of the disease and should be monitored closely at regular intervals.

While not described in the literature, a not uncommon practice to reduce the often present trismus is to pry apart the jaws while the animals is under anesthesia. Often crude tools such as automobile jacks are employed for this purpose! Such procedures are unnecessary, and their benefit, if any, is only short-term. We have not seen a case of trismus due to polymyositis that did not respond to glucocorticoids, but we have seen several animals that have suffered unnecessarily from jaw prying that was of no benefit. Since medical management is effective, there is no reason to attempt to physically overcome the trismus associated with polymyositis, and the temptation to do so should be avoided.


Degenerative myopathies can often be easily confused with canine polymyositis. Indeed, many times the affected muscles are those of mastication and deglutition, although other muscles may be involved as well. It is our experience that when the masticatory muscles are involved in this condition, trismus is not present. Presentation generally is accompanied by muscle wasting, either general or limited to certain areas. Pain and stiffness are not usually part of the history as they are in polymyositis, and weakness and exercise intolerance referable to the affected areas are the major complaints.

Laboratory findings in animals with this condition are variable. Serum CPK levels may not be elevated, depending presumably on the presence of active muscle disease. EMG results may be normal or equivalent to those seen in polymyositis. Muscle biopsy results are also variable, but never are there the signs of inflammation that characterize polymyositis. Frequently, degenerative changes are seen, and they may or may not be associated with attempted regeneration. Occasionally there is evidence of disease of the macrovasculature of muscle, and sometimes the only histopathology reportable is consistent with neurogenic atrophy. Such variability of histopathologic changes surely suggests different pathophysiological mechanisms among these cases. They have been brought together here by the simple fact that they show no signs of inflammation and that the animals affected show no improvement with anti-inflammatory therapy. These cases are rare, but they must be distinguished from canine polymyositis.


Another rare but notorious disease of canine muscle is myotonia. This disease occurs in humans in a variety of forms, some of which are malignant. It also has been recorded in the goat (benign) and in the horse (not benign). In the dog, the disease is most often seen in connection with Cushing's disease of either the natural or iatrogenic type.

As the name suggests, myotonia is associated with an abnormal stiffness of muscular origin. There is considerable laboratory and clinical evidence demonstrating that the abnormality resides in the muscle cell membrane and is electrophysiological in its effects. However, there appears to be more than one type of membrane lesion capable of producing the disease. In the caprine form of myotonia and in at least one form of human myotonia,(10) the manifestations of the disease can be traced to an abnormality (deficiency) in chloride permeability across the muscle membrane. This type of deficiency, be it natural or laboratory-produced, creates an electrical instability in the membrane that leads to self-generated action potentials in the muscle fiber following any normally produced action potential. It is these repetitive action potentials that account for the "dive-bomber" activity that is the EMG hallmark of the disease. It is also from these repetitive secondary potentials that the clinical signs of stiffness are derived. In the canine and equine forms of myotonia and in the more severe forms of disease in humans these secondary repetitive action potentials occur, but they may be of an origin different from the chloride permeability abnormality seen in caprine myotonia, since measurements in these cases have shown chloride conductance to be normal.

In the case of canine myotonia, the diagnosis can be made on the basis of clinical signs and EMG findings. Whenever canine myotonia is encountered, Cushing's disease should be suspected and its presence or absence demonstrated. When hyperadrenocorticalism is found, it should be treated appropriately first. Endocrinologic therapy may or may not relieve the signs of myotonia. If it does not, or if there is no endocrinologic abnormality, treatment of the myotonia per se may be attempted, but success in this approach is minimal. In humans, the drug of choice for the myotonic condition is phenytoin. In the dog this drug is excreted so rapidly and absorbed so poorly(9) that it is rarely effective. Quinidine and procainamide are two other membrane-stabilizing drugs that may prove useful in control of myotonia.


Clinicians who are confronted with a degenerative myopathy or indeed with any myopathy of unknown origin are occasionally tempted to make the diagnosis of canine muscular dystrophy. Unfortunately, this temptation has not been avoided often enough. In humans, the definition

of muscular dystrophy includes two elements: a progressive muscular disease and evidence of genetic transmission.(12) The veterinary profession is hampered in pursuing these two elements-the first because the muscular basis is often difficult and expensive to demonstrate and the second because breeders eliminate weak and sickly animals from their blood lines. While this is a handicap for the myologist, it is no doubt best for the canine population in general. These difficulties notwithstanding, there are reports of muscular dystrophy in the dog,(14) but because of the common breeding practices these cases are very rare.



1. Brown MJ, Martin JR, Ashbury AK: Painful diabetic neuropathy: A morphometnc study. Arch Neurol 33:164, 1976

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3. Cummings JF, deLahunta A: Hypertrophic neuropoathy in a dog. Acta Neuropathol 29:325, 1974

4. Cummings JF, deLahunta A, Lorenz MD et al: Canine brachial plexus neuritis: A syndrome resembling serum neuritis in man. Cornell Vet 63:590, 1973

5. deLahunta A: Veterinary Neuroanatomy and Clinical Neurology. Philadelphia, WB Saunders, 1977

6. Farnbach GC: Myositis in the dog. Compendium on Continuing Education 1:183, 1979

7. Garlepp M, Farrow B. Kay P et al: Antibodies to the acetylcholine receptor in myasthenic dogs. Immunology 37:807, 1979

8. Kornegay JN, Gorgacz EJ, Dawe DL et al: Polymyositis in the dog. J Am Vet Med Assoc 176:431, 1980

9. Kowalczyk DF: Correlation of serum phenytoin with administration of oral and intravenous phenytoin in dogs. J Vet Pharmacol Ther 3:237, 1980

10. Lipicky RJ, Bryant SH, Solomon JH: Cable parameters, sodium, potassium, chloride and water content and potassium efflux in isolated intercostal muscle of normal volunteers and patients with myotonia congenita. J Clin Invest Res 50:2091, 1971

11. Northington JW, Brown MJ, Farnbach GC et al: Acute idiopathic polyneuropathy in the dog. J Am Vet Med Assoc 179:375, 1981

12. Rowlands LP: Are the muscular dystrophies neurogenic? Ann NY Acad Sci 228:244, 1974

13. Soulsby EJL (ed): Helminths, Arthropods and Protozoa of Domestic Animals, 6th ed. Baltimore, Williams & Wilkins, 1968

14. Wentink GH et al: Myopathy with a possible recessive X-linked inheritance in a litter of Irish terriers. Vet Pathol 9:328, 1972