Atypical Myopathy (AM) - similar to Seasonal Pasture Myopathy (SPM)
Equine Atypical Myopathy website (English & French)
PLEASE REPORT ALL CASES TO THE ATYPICAL MYOPATHY ALERT GROUP
Information about AM is changing all the time as more is learned about this newly recognised disease - this is our current understanding but is subject to change.
\June 2013: Atypical Myopathy - Liphook Equine Hospital client update
Atypical Myopathy (AM) is an acute and severe rhabdomyolysis that is not related to exercise, with a high mortality rate (~ 74%), and is found in Europe (UK, France, The Netherlands, Belgium, Germany have reported cases). Very little is known about the disease, but recent research has concluded that AM is caused by a toxin called hypoglycin A found in sycamore seeds (Acer pseudoplatanus) in Europe. In the USA the same toxin has been found in box elder tree seeds (Acer negundo) and causes Seasonal Pasture Myopathy (SPM). AM is known to involve a metabolic defect - multiple acyl-CoA dehydrogenase deficiency (MADD), which blocks fatty acid energy metabolism in the mitochondria, and muscle cells of severely affected horses can be completely depleted of carbohydrates. AM likely involves massive muscle destruction. Horses that die from AM generally do so very quickly, within 1 - 2 days of symptoms being seen, and in recent research all nonsurvivors died or were put down within 10 days of symptoms being seen.
The sycamore is a common member of the maple family found throughout central and southern Europe. It can be recognised by its (now known to be toxic to horses) winged seeds, often called "helicopters", that fall in the autumn. For help identifying sycamore trees see:
www.first-nature.com - Acer pseudoplatanus
www.hedgerowmobile.com - Sycamore
Before the cause was confirmed as sycamore seeds, analysing data from confirmed or suspected cases had suggested the following risk factors:
Horse at pasture/grazing near trees (98%) (particularly maple trees?), fallen leaves (87%), dead wood in the field (61%), sloping pasture(63%), autumn, or autumnal conditions in the spring, sudden change in the weather. Full time grazing increases the risk (86%) - one study found that all horses with AM had spent 6 + hours at pasture/day.
Horse likely to be in normal body condition (87%), rather than underweight?
Exposure to Clostridium sordellii toxin
Exposure to fungi Rhytisma acerinum on dead (maple?) leaves
Symptoms, not specific but suggestive of AM (not all horses with AM show these signs):
pigmenturia (93%) - red to brown coloured urine (presumably from myoglobin?)
normal temperature (64%) (29% hypothermia, 10% hyperthermia)
increased creatine kinase CK (range recorded 634 - 7,059,880 (normal 50-200) IU/L - high CK has been found in both survivors and nonsurvivors and does not appear to be prognostic. Initial CK levels may not be significantly raised, it is recommended that CK is analysed frequently.
congested mucous membranes (53%) (normal mucous membranes 37%)
Tachycardia (increased heart rate) 79%
Difficulty breathing (44%)
Depression, weakness, stiffness, trembling, sweating, often recumbent, may remain standing most of the time
Symptoms that suggest a poor outcome include recumbency (lying down a lot/all the time) (seen in 85% of nonsurvivors, 60% of survivors), sweating (seen in 70% of nonsurvivors, 47% of survivors), not eating (seen in 33% of nonsurvivors, 16% of survivors), increased heart rate (average 62 with range 30 - 120 in nonsurvivors, average 53 with range 28 - 88 in survivors) and respiration rate (average 29 with range 6 - 72 in nonsurvivors, average 24 range 8 - 48 survivors), and difficulty breathing (seen in 52% of nonsurvivors, 19% of survivors).
Symptoms that suggest a more positive outcome include remaining standing, normal temperature, passing dung (seen in 85% of survivors, 62% of nonsurvivors) and normal mucous membrane colour.
Treatment:
Treatment with antioxidants and vitamins - selenium, vitamins B, C and E and carnitine - appears to improve survival - these support muscular function and aerobic metabolism and have anti-oxidant properties.
Research has suggested that supplemental feeding while a horse is at grass may be protective, perhaps because of the increased carbohydrates, vitamins and anti-oxidants, perhaps simply that fed horses will graze less.
If AM is suspected, all horses should be removed from the pasture and stabled - it appears horses can be considered safe if they do not show symptoms after being stabled for at least 5 days.
Prevention:
Fence off sycamore trees when seeds are present, or collect and remove seeds.
Ensure horses have got plenty of grass or additional hay/haylage to eat to make it less likely that they will eat seeds and tree parts.
Supplement food during high risk periods - carbohydrates, antioxidants and vitamins.
The advice before sycamore seeds were identified as the cause was to not graze horses near trees, dead leaves, dead wood.
Stable horses, especially young horses, or limit grazing during the autumn or autumnal weather in the spring;
Recent research has identified a toxin, Hypoglycin A, known to cause MADD, in box elder seeds:
Equine Veterinary Journal Early View, Article first published online: 20 NOV 2012 (Full) (PubMed)
Seasonal pasture myopathy/atypical myopathy in North America associated with ingestion of hypoglycin A within seeds of the box elder tree
S. J. VALBERG, B. T. SPONSELLER, A. D. HEGEMAN, J. EARING, J. B. BENDER, K. L. MARTINSON, S. E. PATTERSON & L. SWEETMAN
"RESULTS: Seeds from box elder trees (Acer negundo) were present on all SPM and 61% of control pastures. Hypoglycin A, known to cause acquired multiple acyl-CoA dehydrogenase deficiency (MADD), was found in box elder seeds. Serum acylcarnitines and urine organic acid profiles in SPM horses were typical for MADD. The hypoglycin A metabolite methylenecyclopropylacetic acid (MCPA), known to be toxic in other species, was found in conjugated form in SPM horse serum and urine. Horses with SPM had longer turn-out, more overgrazed pastures, and less supplemental feeding than control horses.
POTENTIAL RELEVANCE: For the first time, SPM has been linked to a toxin in seeds abundant on autumn pastures whose identified metabolite, MCPA, is known to cause acquired MADD, the pathological mechanism behind SPM and AM. Further research is required to determine the lethal dose of hypoglycin A in horses, as well as factors that affect annual seed burden and hypoglycin A content in Acer species in North America and Europe."
J Vet Intern Med. 2012 Jul-Aug;26(4):1012-8. doi: 10.1111/j.1939-1676.2012.00957.x. Epub 2012 Jun 18. (PubMed)
Equine multiple acyl-CoA dehydrogenase deficiency (MADD) associated with seasonal pasture myopathy in the midwestern United States.
Sponseller BT, Valberg SJ, Schultz NE, Bedford H, Wong DM, Kersh K, Shelton GD.
"CONCLUSIONS AND CLINICAL IMPORTANCE: Similar to AM, the biochemical defect causing SPM is MADD, which causes defective muscular lipid metabolism and excessive myofiber lipid content. Diagnosis can be made by assessing serum acylcarnitine and urine organic acid profiles."
Equine Veterinary Journal Volume 44, Issue 5, pages 621–625, September 2012 (Full)
European outbreaks of atypical myopathy in grazing horses (2006–2009): Determination of indicators for risk and prognostic factors
van GALEN, G., SAEGERMAN, C., MARCILLAUD PITEL, C., PATARIN, F., AMORY, H., BAILY, J. D., CASSART, D., GERBER, V., HAHN, C., HARRIS, P., KEEN, J. A., KIRSCHVINK, N., LEFERE, L., McGORUM, B., MULLER, J. M. V., PICAVET, M. T. J. E., PIERCY, R. J., ROSCHER, K., SERTEYN, D., UNGER, L., van der KOLK, J. H., van LOON, G., VERWILGHEN, D., WESTERMANN, C. M. and VOTION, D. M.
Equine Vet J. 2012 Mar 26. doi: 10.1111/j.2042-3306.2012.00556.x. [Epub ahead of print] (PubMed)
European outbreaks of atypical myopathy in grazing equids (2006-2009): Spatiotemporal distribution, history and clinical features
van Galen G, Marcillaud Pitel C, Saegerman C, Patarin F, Amory H, Baily JD, Cassart D, Gerber V, Hahn C, Harris P, Keen JA, Kirschvink N, Lefere L, McGorum B, Muller JM, Picavet MT, Piercy RJ, Roscher K, Serteyn D, Unger L, van der Kolk JH, van Loon G, Verwilghen D, Westermann CM, Votion DM.
"Of 600 suspected cases, 354 met the diagnostic criteria for confirmed or highly probable AM. The largest outbreaks occurred during the autumns of 2006 and 2009 in Belgium, France and Germany. For the first time, donkeys, zebras and old horses were affected, and clinical signs such as gastrointestinal impaction, diarrhoea, penile prolapse, buccal ulceration and renal dysfunction were observed. Affected horses spent >6 h/day on pastures that almost always contained or were surrounded by trees. The latency period was estimated at up to 4 days. Overall survival rate was 26%. Although differences between countries in affected breeds, body condition, horse management and pasture characteristics were recognised, the common presenting clinical signs and mortality were similar between countries. Conclusions and potential relevance: This study describes new data on case details, history and clinical course of AM that is of preventive, diagnostic and therapeutic value. However, the true impact of the findings of this study on the development of or severity of AM should be tested with case-control studies."
Equine Veterinary Journal Special Issue: Clinical Research Abstracts of the British Equine Veterinary Association Congress 2012
Volume 44, Issue Supplement s42, pages 2–18, September 2012 #21
EQUINE ATYPICAL MYOPATHY: DESCRIPTION OF THE OUTBREAK IN THE NETHERLANDS DURING AUTUMN 2009 AND SPRING 2010
Westermann, C.M. and Sas, A.M.C.
44 likely and 10 confirmed cases of AM in The Netherlands, mortality rate 74.5%, all horses had been on pasture before developing symptoms, 35 had been on pasture near maple trees, 15 of which were known to be infected with the fungi Rhytisma acerinum, and a sudden change in the weather had occurred before the horses started showing symptoms. It is proposed that leaves falling off maple trees and becoming infected with the fungi could be linked to the development of AM.
12th WEVA Congress 2011
Novel insights into the management of atypical myopathy in grazing horses based on recent series of European outbreaks and advances in etiological investigations
D M Votion, V Gerber
Neuromuscul Disord. 2008 May;18(5):355-64. Epub 2008 Apr 11 (PubMed)
Acquired multiple Acyl-CoA dehydrogenase deficiency in 10 horses with atypical myopathy
Westermann CM, Dorland L, Votion DM, de Sain-van der Velden MG, Wijnberg ID, Wanders RJ, Spliet WG, Testerink N, Berger R, Ruiter JP, van der Kolk JH
/2A deficiency of several mitochondrial dehydrogenases that utilize flavin adenine dinucleotide as cofactor including the acyl-CoA dehydrogenases of fatty acid beta-oxidation, and enzymes that degrade the CoA-esters of glutaric acid, isovaleric acid, 2-methylbutyric acid, isobutyric acid, and sarcosine was suspected in 10 out of 10 cases as the possible etiology for a highly fatal and prevalent toxic equine muscle disease similar to the combined metabolic derangements seen in human multiple acyl-CoA dehydrogenase deficiency also known as glutaric acidemia type II."
Seasonal Pasture Myopathy/Atypical Myopathy - University of Minnesota (2012)
BEVA Sept 2011
Atypical myopathy
Dominique-Marie Votion
PLEASE REPORT ALL CASES TO THE ATYPICAL MYOPATHY ALERT GROUP
Information about AM is changing all the time as more is learned about this newly recognised disease - this is our current understanding but is subject to change.
\June 2013: Atypical Myopathy - Liphook Equine Hospital client update
Atypical Myopathy (AM) is an acute and severe rhabdomyolysis that is not related to exercise, with a high mortality rate (~ 74%), and is found in Europe (UK, France, The Netherlands, Belgium, Germany have reported cases). Very little is known about the disease, but recent research has concluded that AM is caused by a toxin called hypoglycin A found in sycamore seeds (Acer pseudoplatanus) in Europe. In the USA the same toxin has been found in box elder tree seeds (Acer negundo) and causes Seasonal Pasture Myopathy (SPM). AM is known to involve a metabolic defect - multiple acyl-CoA dehydrogenase deficiency (MADD), which blocks fatty acid energy metabolism in the mitochondria, and muscle cells of severely affected horses can be completely depleted of carbohydrates. AM likely involves massive muscle destruction. Horses that die from AM generally do so very quickly, within 1 - 2 days of symptoms being seen, and in recent research all nonsurvivors died or were put down within 10 days of symptoms being seen.
The sycamore is a common member of the maple family found throughout central and southern Europe. It can be recognised by its (now known to be toxic to horses) winged seeds, often called "helicopters", that fall in the autumn. For help identifying sycamore trees see:
www.first-nature.com - Acer pseudoplatanus
www.hedgerowmobile.com - Sycamore
Before the cause was confirmed as sycamore seeds, analysing data from confirmed or suspected cases had suggested the following risk factors:
Horse at pasture/grazing near trees (98%) (particularly maple trees?), fallen leaves (87%), dead wood in the field (61%), sloping pasture(63%), autumn, or autumnal conditions in the spring, sudden change in the weather. Full time grazing increases the risk (86%) - one study found that all horses with AM had spent 6 + hours at pasture/day.
Horse likely to be in normal body condition (87%), rather than underweight?
Exposure to Clostridium sordellii toxin
Exposure to fungi Rhytisma acerinum on dead (maple?) leaves
Symptoms, not specific but suggestive of AM (not all horses with AM show these signs):
pigmenturia (93%) - red to brown coloured urine (presumably from myoglobin?)
normal temperature (64%) (29% hypothermia, 10% hyperthermia)
increased creatine kinase CK (range recorded 634 - 7,059,880 (normal 50-200) IU/L - high CK has been found in both survivors and nonsurvivors and does not appear to be prognostic. Initial CK levels may not be significantly raised, it is recommended that CK is analysed frequently.
congested mucous membranes (53%) (normal mucous membranes 37%)
Tachycardia (increased heart rate) 79%
Difficulty breathing (44%)
Depression, weakness, stiffness, trembling, sweating, often recumbent, may remain standing most of the time
Symptoms that suggest a poor outcome include recumbency (lying down a lot/all the time) (seen in 85% of nonsurvivors, 60% of survivors), sweating (seen in 70% of nonsurvivors, 47% of survivors), not eating (seen in 33% of nonsurvivors, 16% of survivors), increased heart rate (average 62 with range 30 - 120 in nonsurvivors, average 53 with range 28 - 88 in survivors) and respiration rate (average 29 with range 6 - 72 in nonsurvivors, average 24 range 8 - 48 survivors), and difficulty breathing (seen in 52% of nonsurvivors, 19% of survivors).
Symptoms that suggest a more positive outcome include remaining standing, normal temperature, passing dung (seen in 85% of survivors, 62% of nonsurvivors) and normal mucous membrane colour.
Treatment:
Treatment with antioxidants and vitamins - selenium, vitamins B, C and E and carnitine - appears to improve survival - these support muscular function and aerobic metabolism and have anti-oxidant properties.
Research has suggested that supplemental feeding while a horse is at grass may be protective, perhaps because of the increased carbohydrates, vitamins and anti-oxidants, perhaps simply that fed horses will graze less.
If AM is suspected, all horses should be removed from the pasture and stabled - it appears horses can be considered safe if they do not show symptoms after being stabled for at least 5 days.
Prevention:
Fence off sycamore trees when seeds are present, or collect and remove seeds.
Ensure horses have got plenty of grass or additional hay/haylage to eat to make it less likely that they will eat seeds and tree parts.
Supplement food during high risk periods - carbohydrates, antioxidants and vitamins.
The advice before sycamore seeds were identified as the cause was to not graze horses near trees, dead leaves, dead wood.
Stable horses, especially young horses, or limit grazing during the autumn or autumnal weather in the spring;
Recent research has identified a toxin, Hypoglycin A, known to cause MADD, in box elder seeds:
Equine Veterinary Journal Early View, Article first published online: 20 NOV 2012 (Full) (PubMed)
Seasonal pasture myopathy/atypical myopathy in North America associated with ingestion of hypoglycin A within seeds of the box elder tree
S. J. VALBERG, B. T. SPONSELLER, A. D. HEGEMAN, J. EARING, J. B. BENDER, K. L. MARTINSON, S. E. PATTERSON & L. SWEETMAN
"RESULTS: Seeds from box elder trees (Acer negundo) were present on all SPM and 61% of control pastures. Hypoglycin A, known to cause acquired multiple acyl-CoA dehydrogenase deficiency (MADD), was found in box elder seeds. Serum acylcarnitines and urine organic acid profiles in SPM horses were typical for MADD. The hypoglycin A metabolite methylenecyclopropylacetic acid (MCPA), known to be toxic in other species, was found in conjugated form in SPM horse serum and urine. Horses with SPM had longer turn-out, more overgrazed pastures, and less supplemental feeding than control horses.
POTENTIAL RELEVANCE: For the first time, SPM has been linked to a toxin in seeds abundant on autumn pastures whose identified metabolite, MCPA, is known to cause acquired MADD, the pathological mechanism behind SPM and AM. Further research is required to determine the lethal dose of hypoglycin A in horses, as well as factors that affect annual seed burden and hypoglycin A content in Acer species in North America and Europe."
J Vet Intern Med. 2012 Jul-Aug;26(4):1012-8. doi: 10.1111/j.1939-1676.2012.00957.x. Epub 2012 Jun 18. (PubMed)
Equine multiple acyl-CoA dehydrogenase deficiency (MADD) associated with seasonal pasture myopathy in the midwestern United States.
Sponseller BT, Valberg SJ, Schultz NE, Bedford H, Wong DM, Kersh K, Shelton GD.
"CONCLUSIONS AND CLINICAL IMPORTANCE: Similar to AM, the biochemical defect causing SPM is MADD, which causes defective muscular lipid metabolism and excessive myofiber lipid content. Diagnosis can be made by assessing serum acylcarnitine and urine organic acid profiles."
Equine Veterinary Journal Volume 44, Issue 5, pages 621–625, September 2012 (Full)
European outbreaks of atypical myopathy in grazing horses (2006–2009): Determination of indicators for risk and prognostic factors
van GALEN, G., SAEGERMAN, C., MARCILLAUD PITEL, C., PATARIN, F., AMORY, H., BAILY, J. D., CASSART, D., GERBER, V., HAHN, C., HARRIS, P., KEEN, J. A., KIRSCHVINK, N., LEFERE, L., McGORUM, B., MULLER, J. M. V., PICAVET, M. T. J. E., PIERCY, R. J., ROSCHER, K., SERTEYN, D., UNGER, L., van der KOLK, J. H., van LOON, G., VERWILGHEN, D., WESTERMANN, C. M. and VOTION, D. M.
Equine Vet J. 2012 Mar 26. doi: 10.1111/j.2042-3306.2012.00556.x. [Epub ahead of print] (PubMed)
European outbreaks of atypical myopathy in grazing equids (2006-2009): Spatiotemporal distribution, history and clinical features
van Galen G, Marcillaud Pitel C, Saegerman C, Patarin F, Amory H, Baily JD, Cassart D, Gerber V, Hahn C, Harris P, Keen JA, Kirschvink N, Lefere L, McGorum B, Muller JM, Picavet MT, Piercy RJ, Roscher K, Serteyn D, Unger L, van der Kolk JH, van Loon G, Verwilghen D, Westermann CM, Votion DM.
"Of 600 suspected cases, 354 met the diagnostic criteria for confirmed or highly probable AM. The largest outbreaks occurred during the autumns of 2006 and 2009 in Belgium, France and Germany. For the first time, donkeys, zebras and old horses were affected, and clinical signs such as gastrointestinal impaction, diarrhoea, penile prolapse, buccal ulceration and renal dysfunction were observed. Affected horses spent >6 h/day on pastures that almost always contained or were surrounded by trees. The latency period was estimated at up to 4 days. Overall survival rate was 26%. Although differences between countries in affected breeds, body condition, horse management and pasture characteristics were recognised, the common presenting clinical signs and mortality were similar between countries. Conclusions and potential relevance: This study describes new data on case details, history and clinical course of AM that is of preventive, diagnostic and therapeutic value. However, the true impact of the findings of this study on the development of or severity of AM should be tested with case-control studies."
Equine Veterinary Journal Special Issue: Clinical Research Abstracts of the British Equine Veterinary Association Congress 2012
Volume 44, Issue Supplement s42, pages 2–18, September 2012 #21
EQUINE ATYPICAL MYOPATHY: DESCRIPTION OF THE OUTBREAK IN THE NETHERLANDS DURING AUTUMN 2009 AND SPRING 2010
Westermann, C.M. and Sas, A.M.C.
44 likely and 10 confirmed cases of AM in The Netherlands, mortality rate 74.5%, all horses had been on pasture before developing symptoms, 35 had been on pasture near maple trees, 15 of which were known to be infected with the fungi Rhytisma acerinum, and a sudden change in the weather had occurred before the horses started showing symptoms. It is proposed that leaves falling off maple trees and becoming infected with the fungi could be linked to the development of AM.
12th WEVA Congress 2011
Novel insights into the management of atypical myopathy in grazing horses based on recent series of European outbreaks and advances in etiological investigations
D M Votion, V Gerber
Neuromuscul Disord. 2008 May;18(5):355-64. Epub 2008 Apr 11 (PubMed)
Acquired multiple Acyl-CoA dehydrogenase deficiency in 10 horses with atypical myopathy
Westermann CM, Dorland L, Votion DM, de Sain-van der Velden MG, Wijnberg ID, Wanders RJ, Spliet WG, Testerink N, Berger R, Ruiter JP, van der Kolk JH
/2A deficiency of several mitochondrial dehydrogenases that utilize flavin adenine dinucleotide as cofactor including the acyl-CoA dehydrogenases of fatty acid beta-oxidation, and enzymes that degrade the CoA-esters of glutaric acid, isovaleric acid, 2-methylbutyric acid, isobutyric acid, and sarcosine was suspected in 10 out of 10 cases as the possible etiology for a highly fatal and prevalent toxic equine muscle disease similar to the combined metabolic derangements seen in human multiple acyl-CoA dehydrogenase deficiency also known as glutaric acidemia type II."
Seasonal Pasture Myopathy/Atypical Myopathy - University of Minnesota (2012)
BEVA Sept 2011
Atypical myopathy
Dominique-Marie Votion