DISEASES OF THE SPINE
0195-5616/92 $0.00 + .20
DEGENERATIVE MYELOPATHY Roger M. Clemmons, DVM, PhD
Degenerative myelopathy (DM) is a neurodegenerative disease that is seen particularly in the German Shepherd. 1-4, 6 DM is a specific disorder characterized by widespread myelin and axon loss beginning in the thoracolumbar area of the spinal cord. The age of onset of DM is between 5 and 7 years. It may be confused with other disorders, including intervertebral disc protrusions, lumbosacral stenosis, and hip dysplasia, which also occur in older dogs. Most of the information about the pathophysiology and immunology of DM has come from studies of German Shepherds afflicted with the disease. Although other large breeds of dogs have been reported to show pathologic changes similar to DM in the German Shepherd, 1,4 immune studies and therapy in OM have been extensively examined only in German Shepherds. 3 As such, the author exercises clinical caution in making the diagnosis of OM in any other breed of dog. If a primary disease, surgical or otherwise, is found in the diagnostic workup of a dog other than the German Shepherd, treatment of the primary problem should be done without regard to OM. On the other hand, even if another disease process is found in a German Shepherd, the possibility of OM must be considered. CLINICAL SIGNS
Clinically OM is characterized by loss of· proprioceptive function, leading to progressive posterior ataxia. The ataxia is initially characterized by knuckling of the toes, wearing of the nails of the inner digits of the rear paws, and stumbling. Signs of hypermetria gradually From the Department of Small Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, Florida VETERINARY CLINICS OF NORTH AMERICA: SMALL ANIMAL PRACTICE VOLUME 22 • NUMBER 4 • JULY 1992
965
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CLEMMONS
develop. Other signs of upper motor neuronal dysfunction, including hyperactive tendon reflexes, crossed extensor reflexes, and Babinski's signs, develop over time. Once these later signs are easily elicited, the chance of therapeutic success is less. Pain sensation is largely spared, and afflicted dogs remain urinary and fecal continent until late in the course of OM. The disease is usually progressive, although fluctuations in clinical signs are frequently seen. The course of the disease is reported to be 6 months to 1 year from the first appearance of clinical signs. I, 4, 6 Patients maintained beyond the loss of rear leg function eventually develop foreleg dysfunction, finally succumbing to brain stem involvement. In some cases, signs of lower motor neuronal dysfunction may be seen. Although these patients account for fewer than 10% of the total number of dogs with OM, the presence of lower motor neuronal signs cannot be used as an exclusionary test for DM. These patients have the same general abnormalities, with the addition of localized motor unit disease characterized by decreased tendon reflexes. One limb is often more severely affected. Most of these dogs have no electromyographic changes, suggesting that the lesions are predominantly in the dorsal nerve roots. 4 It does not appear that this is a separate disease but is instead another manifestation of OM. The prognosis for this form of OM is worse, since the nerve root damage does not appear to be reversible. DIAGNOSIS
A diagnosis of OM should be suspected in any German Shepherd, or perhaps any large-breed dog, with progressive spinal ataxia and weakness. This is supported by the neurologic findings of diffuse thoracolumbar spinal cord dysfunction. Local hyperpathia is, for the most part, absent. The lack of urinary and fecal incontinence early in the course of OM helps rule out significant extradural disease. Results of clinicopathologic examination are generally within normal limits except for an elevation of protein in the cerebrospinal fluid (CSF) from the lumbar cistern. Findings on electromyographic examination are usually normal, supporting the localization of the disease process to the white matter pathways of the spinal cord. Spinal cord evoked potentials recorded over the dorsal aspect of the first cervical vertebrae after stimulation of the sciatic nerve indicate a diminished amplitude and prolonged or separated N I wave. The changes in the evoked potential worsen as the clinical signs of OM progress, suggesting that abnormal spinal cord conduction may be associated with the neurologic abnormalities seen in OM.3 Routine radiographic examination and myelography rule out the presence of significant spinal cord compression or segmental disease. Minor disc protrusions, spondylosis deformans, and osseous dural
DEGENERATIVE MYELOPATHY
967
metaplasia are commonly seen. Many DM patients also have hip dysplasia. Depressed cell-mediated immune responses to concanavalin A, phytohemagglutinin P,6 and pokeweed mitogen have been found to be a reliable laboratory test, in the presence of typical clinical signs, for the diagnosis of DM.3 Cell-mediated immune studies correlate with the presence and the severity of the disorder. These immune studies are of particular value when surgical procedures that could result in permanent neurologic deterioration are being considered. In those cases in which the cell-mediated immune responses are normal, treatment of the other identifiable cause of clinical signs has usually been beneficial. Circulating immune complexes are elevated in the sera of patients with DM. Moreover because the presence of specific circulating immune complexes appears to precede the development of immune deficits and clinical signs (in preliminary investigations), it appears that the immune complexes, by nature of their processing by circulating suppressor macrophages, are responsible for the depressed immune responses in DM. As such, it appears that DM is related to an immune dysfunction, by which abnormal antigen processing is associated with a chronic and progressive neurodegeneration. It is most likely that the elevations in circulating immune complexes and subsequent reduction in cell-mediated immunity are not the cause of DM but a response to the disease process within the nervous system. The development of serum markers for the specific diagnosis of DM seems to be possible. Preliminary investigations using one of these serum markers (85,000 molecular weight), uncovered through examination of circulating immune complexes, has been useful in confirming the presence of DM. Until the technique of isolating the antigenic components of the immune complexes has been perfected, the diagnosis of DM is best made on the clinical signs and history. Ruling out other disorders by careful examination of the differential diagnosis, including the use of myelographic examination, increases the confidence of the diagnosis. In the German Shepherd, at least, quantitation of total immune complexes or examination of lymphocyte blastogenesis to T cell mitogens may be used to provide additional support to the diagnosis ofDM. PATHOPHYSIOLOGY
The pathologic findings seen in DM have been thoroughly described;1, 2/ 4 however, the etiology of DM remains uncertain. Briefly, the pathologic changes most often reported in DM are loss of myelin and axons in the spinal cord that begins in the upper thoracic region. Whether the myelin is lost before or after axons is still unclear, but the most striking feature is that of decreased myelin in the white matter of the spinal cord. In addition, there is sclerosis caused by increased cellular and vascular elements in the regions of the most severe lesions.
968
CLEMMONS
The most probable hypothesis is that DM represents an immunerelated neurodegenerative disease. This is supported by the presence of altered cell-mediated immune responses,6 the presence of circulating suppressor cells,S the presence of elevated circulating immune complexes (some of which appear to be disease specific),3 and the presence of plasma cell infiltrates in several organ systems, including the kidneys and intestinal tracts on necropsy examination. The immune dysfunction in DM, however, is probably not the cause of DM, rather a sign of the widespread nervous system pathology. Any theory of the etiology of DM must take into account these immune changes. Several investigators have proposed possible causes to explain the disease processes in DM. Nutritional factors have been thought to play a role because serum levels of vitamin B12 and vitamin E have been shown to be lower. 7, 8 One the other hand, providing additional nutritional support by replacing these vitamins has not altered the natural course of the disease. Studies are in progress that examine whether the tissue levels and the biologic activity of vitamin E are adequate in DM. Although no direct evidence for an infectious agent in DM has been found either by routine or electron microscopy, it is possible that DM is caused by a combination of genetic predisposition and exposure to an infectious agent. Whether DM represents a possible canine retrovirus infection or represents infection with a "scrapie-like" prion organism is under investigation. Serologic studies and transmission studies by injection of DM spinal cord tissue extract in other animal species, including weanling hamsters and newborn mice, have been inconclusive. No immediate pathology has been seen in these studies. Whether continued serial passage of tissues would lead to adaptation of an organism in such studies has not been determined.
TREATMENT The treatment program that has been found to be most successful includes a combination of exercise, vitamin support, and specific therapy with aminocaproic acid (EACA). The combination is much more effective than one part of the therapy alone. Although many other modes of therapy have been investigated, none is as effective. Exercise plays an important role in delaying the progression of the disease. We recommend an alternate-day exercise program including walking, running (if possible), and swimming. It is important to increase gradually the level of exercise to 30 minutes twice a week and 1 hour once a week. Although this is not always possible at first, it is a goal toward which the owners should strive. Allowing the patient free access to an outside exercise area is not adequate. Patients who do not receive this exercise owing to lack of owner compliance or inability of the owners to comply appear to have a poor prognosis. Sometimes this requires creative instruction by the veterinarian to help the owner in
DEGENERATIVE MYELOPATHY
969
achieving the goal. For example, hiring someone to provide the needed exercise can help owners who cannot physically exercise their animal. Although vitamins do not prevent DM progression, certain vitamin support appears to be beneficial. We recommend a high-potency vitamin B complex (stress tablets) twice a day, since this might provide support for neuroregeneration. Vitamin E (at 2000 IU/day) provides a nonsteroidal anti-inflammatory (NSAI) action and helps delay the progression of the signs of DM. Unfortunately it does not prevent the eventual deterioration from OM. Because vitamin E provides a NSAI action, we do not recommend the concurrent use of other NSAI drugs. If analgesia is needed, acetaminophen (Tylenol) may be given at 5 mg/ kg, not to exceed 20 mglkg/day. If further analgesia or anti-inflammatory action is required, the daily dose of vitamin E should be reduced to 100 IU/day for 3 to 6 days and the appropriate NSAI drug added to the patient's therapy. The only medication that the author has found that appears to alter the natural course of OM is EACA. The mechanism by which EACA exerts its beneficial actions is not clear. Clinically EACA therapy appears to prevent the progression or decrease the continued rate of progression of DM, suggesting that EACA works by blocking a final common pathway for neural tissue destruction. The rate of progression seems reduced by 50% in most patients. Moreover in approximately 15% to 20% of the cases, the condition appears to halt or improve while the patient receives EACA. Over the past 10 years, the author has used the tablet form of EACA to treat patients with DM.3 Owing to the expense of the trade drug (the only way the tablets are available), however, the author has switched to using the generic injectable form of EACA as an oral solution. Our experience to date indicates that the generic drug used in this manner is as effective, if not more effective, than the earlier tablet form. It has the major advantage of being much less expensive. To provide 1 month's supply of the drug, we mix 192 mL of EACA (250 mg/mL for injection) with 96 mL of a hematinic compound (Lixotinic), creating a solution (288 mL) that provides 500 mg of EACA in each 3 mL of the solution. This should be refrigerated between doses. The dose of EACA is 500 mg every 8 hours. After beginning EACA therapy, clinical improvement will generally be seen within the first 8 weeks of therapy. Costlbenefit must be weighed carefully in those patients who do not respond by stabilization or remission of clinical signs. There is probably no benefit in those patients who are already paralyzed by DM, yet they should, at least, receive a trial with EACA, since some improve. The only side effect that has been seen with the tablet form of EACA has been rare gastrointestinal upset (1 % of cases), usually in patients with existing irritative colitis. 3 With the generic form of the drug, given orally, some patients experience inappetence at the start of the medication (5% of cases). This has usually been resolved by giving the drug with or following a small amount of food. Some patients experience borborygmus and flatulence secondary to the hematinic product. In those instances, the EACA solution is given alone. The
970
CLEMMONS
hematinic does, however, improve the taste of the medication. At the doses used to treat OM, there have been no cardiovascular, neuromuscular, or hematologic abnormalities noted. In the past, the treatment of OM was with corticosteroids, even though corticosteroids do not halt the progression of the disease. In fact, the long-term use of high doses of corticosteroids can increase muscle wasting and lead to greater speed of deterioration owing to their catabolic properties. Corticosteroids can help in the treatment of exacerbations that occur during the course of OM. Once the exacerbation is under control, it is best to stop the corticosteroid until a new exacerbation occurs. The method of corticosteroid dosing that we recommend is prednisone in a decreasing regimen beginning at an initial level of 1 mg/kg/day given in 3 equal doses for 3 days. This is reduced to 0.33 mg/kg every 12 hours for 2 days. A maintenance dosage of 0.5 mglkg every other day, in the morning, is continued for about 2 weeks (3 weeks of total corticosteroid therapy) or until remission has occurred. If there is no improvement in the first 5 days, or worsening occurs, further corticosteroid usage is probably not indicated. The current recommendation of OM therapy is exercise, vitamin supplementation, judicious use of glucocorticoids, and trials with EACA. If EACA is effective, improvement will usually be seen within 8 weeks of the initiation of therapy. Accurate and early diagnosis of OM is essential, since the chances of successful therapy are markedly improved if therapy is begun early in the course of the disease. German Shepherds with OM can have concurrent disease such as cauda equina syndrome or disc protrusion. Because surgery can markedly worsen clinical signs in OM patients, OM should be excluded before considering surgical intervention. SUMMARY
OM in the German Shepherd is an immune-related disorder whose clinical signs are explained by a widespread degeneration of the white matter pathways in the thoracolumbar spinal cord. Therapy includes exercise, vitamin supplementation, and EACA medication. Avoiding unnecessary surgical procedures is also important to preclude permanent deterioration that can result following surgery in OM patients. In dogs other than German Shepherds, other identifiable causes should be treated. Additional confirmation of the diagnosis of DM may be assisted by performing cell-mediated immune studies or other serodiagnostic tests as they become available. References 1. Averill DR: Degenerative myelopathy in the aging German shepherd dog: Clinical and pathologic findings. J Am Vet Med Assoc 162:1045, 1973
DEGENERATIVE MYELOPATHY
971
2. Braund KG, Vandevelde M: German shepherd dog myelopathy-a morphologic and morphometric study. Am J Vet Res 39:1309, 1978 3. Clemmons RM: Degenerative myelopathy. In Kirk RW, ed: Current Veterinary Therapy x. Philadelphia, WB Saunders, 1989, p 830 4. Griffith IR, Duncan 10: Chronic degenerative radiculomyelopathy in the dog. J Small Anim Pract 16:461, 1975 5. Waxman FJ, Clemmons RM, Hinrichs OJ: Progressive myelopathy in older German shepherd dogs. II. Presence of circulating suppressor cells. J Immunol 124:1216, 1980 6. Waxman FJ, Clemmons RM, Johnson G, et al: Progressive myelopathy in older German shepherd dogs. I. Depressed responses to thymus-dependent mitogens. J ImmunoI124:1209, 1980 7. Williams DA, Batt RM, Sharp NJH: Degenerative myelopathy in German shepherd dogs: An association with mucosal biochemical changes and bacterial overgrowth in the small intestines. Clin Sci 66:25P, 1984 8. Williams DA, Prymak C, Baughan J: Tocopherol (vitamin E) status in canine degenerative myelopathy. In Proceedings of the 3rd Annual Veterinary Medical Forum, 1985, p 154
Address reprint requests to Roger M. Clemmons, DVM, PhD Department of Small Animal Clinical Sciences University of Florida College of Veterinary Medicine Gainesville, FL 32610
0195-5616/92 $0.00 + .20
DEGENERATIVE MYELOPATHY Roger M. Clemmons, DVM, PhD
Degenerative myelopathy (DM) is a neurodegenerative disease that is seen particularly in the German Shepherd. 1-4, 6 DM is a specific disorder characterized by widespread myelin and axon loss beginning in the thoracolumbar area of the spinal cord. The age of onset of DM is between 5 and 7 years. It may be confused with other disorders, including intervertebral disc protrusions, lumbosacral stenosis, and hip dysplasia, which also occur in older dogs. Most of the information about the pathophysiology and immunology of DM has come from studies of German Shepherds afflicted with the disease. Although other large breeds of dogs have been reported to show pathologic changes similar to DM in the German Shepherd, 1,4 immune studies and therapy in OM have been extensively examined only in German Shepherds. 3 As such, the author exercises clinical caution in making the diagnosis of OM in any other breed of dog. If a primary disease, surgical or otherwise, is found in the diagnostic workup of a dog other than the German Shepherd, treatment of the primary problem should be done without regard to OM. On the other hand, even if another disease process is found in a German Shepherd, the possibility of OM must be considered. CLINICAL SIGNS
Clinically OM is characterized by loss of· proprioceptive function, leading to progressive posterior ataxia. The ataxia is initially characterized by knuckling of the toes, wearing of the nails of the inner digits of the rear paws, and stumbling. Signs of hypermetria gradually From the Department of Small Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, Florida VETERINARY CLINICS OF NORTH AMERICA: SMALL ANIMAL PRACTICE VOLUME 22 • NUMBER 4 • JULY 1992
965
966
CLEMMONS
develop. Other signs of upper motor neuronal dysfunction, including hyperactive tendon reflexes, crossed extensor reflexes, and Babinski's signs, develop over time. Once these later signs are easily elicited, the chance of therapeutic success is less. Pain sensation is largely spared, and afflicted dogs remain urinary and fecal continent until late in the course of OM. The disease is usually progressive, although fluctuations in clinical signs are frequently seen. The course of the disease is reported to be 6 months to 1 year from the first appearance of clinical signs. I, 4, 6 Patients maintained beyond the loss of rear leg function eventually develop foreleg dysfunction, finally succumbing to brain stem involvement. In some cases, signs of lower motor neuronal dysfunction may be seen. Although these patients account for fewer than 10% of the total number of dogs with OM, the presence of lower motor neuronal signs cannot be used as an exclusionary test for DM. These patients have the same general abnormalities, with the addition of localized motor unit disease characterized by decreased tendon reflexes. One limb is often more severely affected. Most of these dogs have no electromyographic changes, suggesting that the lesions are predominantly in the dorsal nerve roots. 4 It does not appear that this is a separate disease but is instead another manifestation of OM. The prognosis for this form of OM is worse, since the nerve root damage does not appear to be reversible. DIAGNOSIS
A diagnosis of OM should be suspected in any German Shepherd, or perhaps any large-breed dog, with progressive spinal ataxia and weakness. This is supported by the neurologic findings of diffuse thoracolumbar spinal cord dysfunction. Local hyperpathia is, for the most part, absent. The lack of urinary and fecal incontinence early in the course of OM helps rule out significant extradural disease. Results of clinicopathologic examination are generally within normal limits except for an elevation of protein in the cerebrospinal fluid (CSF) from the lumbar cistern. Findings on electromyographic examination are usually normal, supporting the localization of the disease process to the white matter pathways of the spinal cord. Spinal cord evoked potentials recorded over the dorsal aspect of the first cervical vertebrae after stimulation of the sciatic nerve indicate a diminished amplitude and prolonged or separated N I wave. The changes in the evoked potential worsen as the clinical signs of OM progress, suggesting that abnormal spinal cord conduction may be associated with the neurologic abnormalities seen in OM.3 Routine radiographic examination and myelography rule out the presence of significant spinal cord compression or segmental disease. Minor disc protrusions, spondylosis deformans, and osseous dural
DEGENERATIVE MYELOPATHY
967
metaplasia are commonly seen. Many DM patients also have hip dysplasia. Depressed cell-mediated immune responses to concanavalin A, phytohemagglutinin P,6 and pokeweed mitogen have been found to be a reliable laboratory test, in the presence of typical clinical signs, for the diagnosis of DM.3 Cell-mediated immune studies correlate with the presence and the severity of the disorder. These immune studies are of particular value when surgical procedures that could result in permanent neurologic deterioration are being considered. In those cases in which the cell-mediated immune responses are normal, treatment of the other identifiable cause of clinical signs has usually been beneficial. Circulating immune complexes are elevated in the sera of patients with DM. Moreover because the presence of specific circulating immune complexes appears to precede the development of immune deficits and clinical signs (in preliminary investigations), it appears that the immune complexes, by nature of their processing by circulating suppressor macrophages, are responsible for the depressed immune responses in DM. As such, it appears that DM is related to an immune dysfunction, by which abnormal antigen processing is associated with a chronic and progressive neurodegeneration. It is most likely that the elevations in circulating immune complexes and subsequent reduction in cell-mediated immunity are not the cause of DM but a response to the disease process within the nervous system. The development of serum markers for the specific diagnosis of DM seems to be possible. Preliminary investigations using one of these serum markers (85,000 molecular weight), uncovered through examination of circulating immune complexes, has been useful in confirming the presence of DM. Until the technique of isolating the antigenic components of the immune complexes has been perfected, the diagnosis of DM is best made on the clinical signs and history. Ruling out other disorders by careful examination of the differential diagnosis, including the use of myelographic examination, increases the confidence of the diagnosis. In the German Shepherd, at least, quantitation of total immune complexes or examination of lymphocyte blastogenesis to T cell mitogens may be used to provide additional support to the diagnosis ofDM. PATHOPHYSIOLOGY
The pathologic findings seen in DM have been thoroughly described;1, 2/ 4 however, the etiology of DM remains uncertain. Briefly, the pathologic changes most often reported in DM are loss of myelin and axons in the spinal cord that begins in the upper thoracic region. Whether the myelin is lost before or after axons is still unclear, but the most striking feature is that of decreased myelin in the white matter of the spinal cord. In addition, there is sclerosis caused by increased cellular and vascular elements in the regions of the most severe lesions.
968
CLEMMONS
The most probable hypothesis is that DM represents an immunerelated neurodegenerative disease. This is supported by the presence of altered cell-mediated immune responses,6 the presence of circulating suppressor cells,S the presence of elevated circulating immune complexes (some of which appear to be disease specific),3 and the presence of plasma cell infiltrates in several organ systems, including the kidneys and intestinal tracts on necropsy examination. The immune dysfunction in DM, however, is probably not the cause of DM, rather a sign of the widespread nervous system pathology. Any theory of the etiology of DM must take into account these immune changes. Several investigators have proposed possible causes to explain the disease processes in DM. Nutritional factors have been thought to play a role because serum levels of vitamin B12 and vitamin E have been shown to be lower. 7, 8 One the other hand, providing additional nutritional support by replacing these vitamins has not altered the natural course of the disease. Studies are in progress that examine whether the tissue levels and the biologic activity of vitamin E are adequate in DM. Although no direct evidence for an infectious agent in DM has been found either by routine or electron microscopy, it is possible that DM is caused by a combination of genetic predisposition and exposure to an infectious agent. Whether DM represents a possible canine retrovirus infection or represents infection with a "scrapie-like" prion organism is under investigation. Serologic studies and transmission studies by injection of DM spinal cord tissue extract in other animal species, including weanling hamsters and newborn mice, have been inconclusive. No immediate pathology has been seen in these studies. Whether continued serial passage of tissues would lead to adaptation of an organism in such studies has not been determined.
TREATMENT The treatment program that has been found to be most successful includes a combination of exercise, vitamin support, and specific therapy with aminocaproic acid (EACA). The combination is much more effective than one part of the therapy alone. Although many other modes of therapy have been investigated, none is as effective. Exercise plays an important role in delaying the progression of the disease. We recommend an alternate-day exercise program including walking, running (if possible), and swimming. It is important to increase gradually the level of exercise to 30 minutes twice a week and 1 hour once a week. Although this is not always possible at first, it is a goal toward which the owners should strive. Allowing the patient free access to an outside exercise area is not adequate. Patients who do not receive this exercise owing to lack of owner compliance or inability of the owners to comply appear to have a poor prognosis. Sometimes this requires creative instruction by the veterinarian to help the owner in
DEGENERATIVE MYELOPATHY
969
achieving the goal. For example, hiring someone to provide the needed exercise can help owners who cannot physically exercise their animal. Although vitamins do not prevent DM progression, certain vitamin support appears to be beneficial. We recommend a high-potency vitamin B complex (stress tablets) twice a day, since this might provide support for neuroregeneration. Vitamin E (at 2000 IU/day) provides a nonsteroidal anti-inflammatory (NSAI) action and helps delay the progression of the signs of DM. Unfortunately it does not prevent the eventual deterioration from OM. Because vitamin E provides a NSAI action, we do not recommend the concurrent use of other NSAI drugs. If analgesia is needed, acetaminophen (Tylenol) may be given at 5 mg/ kg, not to exceed 20 mglkg/day. If further analgesia or anti-inflammatory action is required, the daily dose of vitamin E should be reduced to 100 IU/day for 3 to 6 days and the appropriate NSAI drug added to the patient's therapy. The only medication that the author has found that appears to alter the natural course of OM is EACA. The mechanism by which EACA exerts its beneficial actions is not clear. Clinically EACA therapy appears to prevent the progression or decrease the continued rate of progression of DM, suggesting that EACA works by blocking a final common pathway for neural tissue destruction. The rate of progression seems reduced by 50% in most patients. Moreover in approximately 15% to 20% of the cases, the condition appears to halt or improve while the patient receives EACA. Over the past 10 years, the author has used the tablet form of EACA to treat patients with DM.3 Owing to the expense of the trade drug (the only way the tablets are available), however, the author has switched to using the generic injectable form of EACA as an oral solution. Our experience to date indicates that the generic drug used in this manner is as effective, if not more effective, than the earlier tablet form. It has the major advantage of being much less expensive. To provide 1 month's supply of the drug, we mix 192 mL of EACA (250 mg/mL for injection) with 96 mL of a hematinic compound (Lixotinic), creating a solution (288 mL) that provides 500 mg of EACA in each 3 mL of the solution. This should be refrigerated between doses. The dose of EACA is 500 mg every 8 hours. After beginning EACA therapy, clinical improvement will generally be seen within the first 8 weeks of therapy. Costlbenefit must be weighed carefully in those patients who do not respond by stabilization or remission of clinical signs. There is probably no benefit in those patients who are already paralyzed by DM, yet they should, at least, receive a trial with EACA, since some improve. The only side effect that has been seen with the tablet form of EACA has been rare gastrointestinal upset (1 % of cases), usually in patients with existing irritative colitis. 3 With the generic form of the drug, given orally, some patients experience inappetence at the start of the medication (5% of cases). This has usually been resolved by giving the drug with or following a small amount of food. Some patients experience borborygmus and flatulence secondary to the hematinic product. In those instances, the EACA solution is given alone. The
970
CLEMMONS
hematinic does, however, improve the taste of the medication. At the doses used to treat OM, there have been no cardiovascular, neuromuscular, or hematologic abnormalities noted. In the past, the treatment of OM was with corticosteroids, even though corticosteroids do not halt the progression of the disease. In fact, the long-term use of high doses of corticosteroids can increase muscle wasting and lead to greater speed of deterioration owing to their catabolic properties. Corticosteroids can help in the treatment of exacerbations that occur during the course of OM. Once the exacerbation is under control, it is best to stop the corticosteroid until a new exacerbation occurs. The method of corticosteroid dosing that we recommend is prednisone in a decreasing regimen beginning at an initial level of 1 mg/kg/day given in 3 equal doses for 3 days. This is reduced to 0.33 mg/kg every 12 hours for 2 days. A maintenance dosage of 0.5 mglkg every other day, in the morning, is continued for about 2 weeks (3 weeks of total corticosteroid therapy) or until remission has occurred. If there is no improvement in the first 5 days, or worsening occurs, further corticosteroid usage is probably not indicated. The current recommendation of OM therapy is exercise, vitamin supplementation, judicious use of glucocorticoids, and trials with EACA. If EACA is effective, improvement will usually be seen within 8 weeks of the initiation of therapy. Accurate and early diagnosis of OM is essential, since the chances of successful therapy are markedly improved if therapy is begun early in the course of the disease. German Shepherds with OM can have concurrent disease such as cauda equina syndrome or disc protrusion. Because surgery can markedly worsen clinical signs in OM patients, OM should be excluded before considering surgical intervention. SUMMARY
OM in the German Shepherd is an immune-related disorder whose clinical signs are explained by a widespread degeneration of the white matter pathways in the thoracolumbar spinal cord. Therapy includes exercise, vitamin supplementation, and EACA medication. Avoiding unnecessary surgical procedures is also important to preclude permanent deterioration that can result following surgery in OM patients. In dogs other than German Shepherds, other identifiable causes should be treated. Additional confirmation of the diagnosis of DM may be assisted by performing cell-mediated immune studies or other serodiagnostic tests as they become available. References 1. Averill DR: Degenerative myelopathy in the aging German shepherd dog: Clinical and pathologic findings. J Am Vet Med Assoc 162:1045, 1973
DEGENERATIVE MYELOPATHY
971
2. Braund KG, Vandevelde M: German shepherd dog myelopathy-a morphologic and morphometric study. Am J Vet Res 39:1309, 1978 3. Clemmons RM: Degenerative myelopathy. In Kirk RW, ed: Current Veterinary Therapy x. Philadelphia, WB Saunders, 1989, p 830 4. Griffith IR, Duncan 10: Chronic degenerative radiculomyelopathy in the dog. J Small Anim Pract 16:461, 1975 5. Waxman FJ, Clemmons RM, Hinrichs OJ: Progressive myelopathy in older German shepherd dogs. II. Presence of circulating suppressor cells. J Immunol 124:1216, 1980 6. Waxman FJ, Clemmons RM, Johnson G, et al: Progressive myelopathy in older German shepherd dogs. I. Depressed responses to thymus-dependent mitogens. J ImmunoI124:1209, 1980 7. Williams DA, Batt RM, Sharp NJH: Degenerative myelopathy in German shepherd dogs: An association with mucosal biochemical changes and bacterial overgrowth in the small intestines. Clin Sci 66:25P, 1984 8. Williams DA, Prymak C, Baughan J: Tocopherol (vitamin E) status in canine degenerative myelopathy. In Proceedings of the 3rd Annual Veterinary Medical Forum, 1985, p 154
Address reprint requests to Roger M. Clemmons, DVM, PhD Department of Small Animal Clinical Sciences University of Florida College of Veterinary Medicine Gainesville, FL 32610
