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==Introduction==

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==Description==

A progressive, infectious,<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>neurological disease of horses, endemic in the USA<ref name="EPM8">Gray, L.C, Magdesian, K.G, Sturges, B.K, Madigan, J.E (2001) Suspected protozoal myeloencephalitis in a two-month-old colt.  ''Vet Rec'', 149:269-273.</ref> and only encountered elsewhere in equids that have travelled in the Americas.<ref name="EPM3">Vatistas, N, Mayhew, J (1995) Differential diagnosis of polyneuritis equi.  ''In Practice'', Jan, 26-29.</ref>  Equine protozoal myeloencephalitis (EPM) is one of the most frequently diagnosed neurological conditions in the Western Hemisphere<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref> and the principal differential for multifocal, asymmetric progressive central nervous system (CNS) disease.<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>  The disease is not contagious.<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''', (Third edition), ''SUDZ Publishing'', 245-250.</ref>

A progressive, infectious,<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>neurological disease of horses, endemic in the USA<ref name="EPM8">Gray, L.C, Magdesian, K.G, Sturges, B.K, Madigan, J.E (2001) Suspected protozoal myeloencephalitis in a two-month-old colt.  ''Vet Rec'', 149:269-273.</ref> and only encountered elsewhere in equids that have travelled in the Americas.<ref name="EPM3">Vatistas, N, Mayhew, J (1995) Differential diagnosis of polyneuritis equi.  ''In Practice'', Jan, 26-29.</ref>  Equine protozoal myeloencephalitis (EPM) is one of the most frequently diagnosed neurological conditions in the Western Hemisphere<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref> and the principal differential for multifocal, asymmetric progressive central nervous system (CNS) disease.<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>  The disease is not contagious.<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''', (Third edition), ''SUDZ Publishing'', 245-250.</ref>

==Aetiology==

==Aetiology==

EPM results from infection of the CNS by the apicomplexan parasite ''Sarcocystis neurona'' or, less frequently, its close relative ''Neospora hughesi''.<ref>Dubey, J.P, Lindsay, D.S, Saville, W.J, Reed, S.M, Granstrom, D.E, Speer, C.A (2001)A review of ''Sarcocystis neurona'' and equine protozoal myeloencephalitis (EPM). ''Vet Parasitol'', 95:89-131. In: Pusterla, N, Wilson, W.D, Conrad, P.A, Barr, B.C, Ferraro, G.L, Daft, B.M, Leutenegger, C.M (2006) Cytokine gene signatures in neural tissue of horses with equine protozoal myeloencephalitis or equine herpes type 1 myeloencephalopathy.  ''Vet Rec'', Sep 9:''Papers & Articles''.</ref><ref>Wobeser, B.K, Godson, D.L, Rejmanek, D, Dowling, P (2009) Equine protozoal myeloencephalitis caused by ''Neospora hughesi'' in an adult horse in Saskatchewan.  ''Can Vet J'', 50(8):851-3.</ref>  These protozoans develop within neurons<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  causing immediate or inflammatory-mediated neuronal damage.  The organisms migrate randomly through the brain and spinal cord causing asymmetrical lesions of grey and white matter and thus multifocal lower and upper motor neuron deficits.<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>

EPM results from infection of the CNS by the apicomplexan parasite [[Sarcocystis|''Sarcocystis neurona'']] or, less frequently, its close relative [[Neospora|''Neospora hughesi'']].<ref>Dubey, J.P, Lindsay, D.S, Saville, W.J, Reed, S.M, Granstrom, D.E, Speer, C.A (2001)A review of ''Sarcocystis neurona'' and equine protozoal myeloencephalitis (EPM). ''Vet Parasitol'', 95:89-131. In: Pusterla, N, Wilson, W.D, Conrad, P.A, Barr, B.C, Ferraro, G.L, Daft, B.M, Leutenegger, C.M (2006) Cytokine gene signatures in neural tissue of horses with equine protozoal myeloencephalitis or equine herpes type 1 myeloencephalopathy.  ''Vet Rec'', Sep 9:''Papers & Articles''.</ref><ref>Wobeser, B.K, Godson, D.L, Rejmanek, D, Dowling, P (2009) Equine protozoal myeloencephalitis caused by ''Neospora hughesi'' in an adult horse in Saskatchewan.  ''Can Vet J'', 50(8):851-3.</ref>  These protozoans develop within neurons<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  causing immediate or inflammatory-mediated neuronal damage.  The organisms migrate randomly through the brain and spinal cord causing asymmetrical lesions of grey and white matter and thus multifocal lower and upper motor neuron deficits.<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>

==Epidemiology==

==Epidemiology==

[[Image:Equine_Protozoal_Myeloencephalitis_life_cycle.jpg|600px|thumb|centre|''' Life cycle diagram of ''Sarcocystis neurona''.  Created by the ''Agricultural Research Service, the research agency of the United States Department of Agriculture'', July 2005.  ''Sourced from the USDA Agricultural Research Service page on EPM/Sarcocystis neurona, located via WikiMedia Commons.'' ''']]

[[Image:Equine_Protozoal_Myeloencephalitis_life_cycle.jpg|600px|thumb|centre|''' Life cycle diagram of ''Sarcocystis neurona''.  Created by the ''Agricultural Research Service, the research agency of the United States Department of Agriculture'', July 2005.  ''Sourced from the USDA Agricultural Research Service page on EPM/Sarcocystis neurona, located via WikiMedia Commons.'' ''']]

Infective sporocysts are passed in the faeces of the definitive host and must be ingested by the horse for infection to occur.  See [[Sarcocystis|here]] for further details of the life cycle of ''Sarcocystis neurona''.

Infective sporocysts are passed in the faeces of the definitive host and must be ingested by the horse for infection to occur.  See [[Sarcocystis|the ''Sarcocystis'' page]] for further details of the life cycle of ''S.neurona''.

==Pathogenesis==

==Pathogenesis==

It is difficult to obtain a definitive antemortem diagnosis of EPM.  Certain criteria must be met before such a diagnosis is assigned<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>:

It is difficult to obtain a definitive antemortem diagnosis of EPM.  Certain criteria must be met before such a diagnosis is assigned<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>:

*The relevant clinical signs must be attributable to one or more lesions of the CNS<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>

*The relevant clinical signs must be attributable to one or more lesions of the CNS<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>

*Immunodiognostic tests must confirm exposure to the parasite

*Immunodiagnostic tests must confirm exposure to the parasite

*Other differentials with similar presentations should be ruled out wherever possible

*Other differentials with similar presentations should be ruled out wherever possible

*The horse should be resident in or have travelled within the Americas<ref name="EPM3">Vatistas, N, Mayhew, J (1995) Differential diagnosis of polyneuritis equi.  ''In Practice'', Jan, 26-29.</ref>

*The horse should be resident in or have travelled within the Americas<ref name="EPM3">Vatistas, N, Mayhew, J (1995) Differential diagnosis of polyneuritis equi.  ''In Practice'', Jan, 26-29.</ref>

The primary step in the diagnostic procedure should be to carry out thorough clinical and neurological examinations. <ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>  

The primary step in the diagnostic procedure should be to carry out thorough clinical and [[:Category:Neurological Examination - Horse|neurological examinations]]. <ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>  

===Immunodiagnostic  tests===

===Immunodiagnostic  tests===

|Plain lateral radiography of C1 to T1<ref name="Hahn">Hahn, C.N (2010) ''Cervical Vertebral Malformation'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>, myelography. <ref name="Seino">Seino, K.K (2010) ''Spinal Ataxia'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 3.</ref>

|Plain lateral radiography of C1 to T1<ref name="Hahn">Hahn, C.N (2010) ''Cervical Vertebral Malformation'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>, myelography. <ref name="Seino">Seino, K.K (2010) ''Spinal Ataxia'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 3.</ref>

|-

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|West Nile encephalitis

|[[West Nile Virus|West Nile encephalitis]]

|Systemically ill, pyrexia.  Difficult to differentiate if horse is afebrile and has no excessive muscle fasciculations.<ref name="Long">Long, M.T (2010) ''Flavivirus Encephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  

|Systemically ill, pyrexia.  Difficult to differentiate if horse is afebrile and has no excessive muscle fasciculations.<ref name="Long">Long, M.T (2010) ''Flavivirus Encephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  

|Leukogram, CSF analysis, IgM capture ELISA, plaque reduction neutralization test (PRNT),<ref name="Seino">Seino, K.K (2010) ''Spinal Ataxia'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 3.</ref>absence of mosquito vectors.<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>

|Leukogram, CSF analysis, IgM capture ELISA, plaque reduction neutralization test (PRNT),<ref name="Seino">Seino, K.K (2010) ''Spinal Ataxia'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 3.</ref>absence of mosquito vectors.<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>

|Leukogram, IgM ELISA<ref>Bertone, J.J (2010) ''Viral Encephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

|Leukogram, IgM ELISA<ref>Bertone, J.J (2010) ''Viral Encephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

|-

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|Equine herpesvirus-1 myeloencephalopathy  

|[[Equine Herpesvirus 1|Equine herpesvirus-1 myeloencephalopathy]]

|Sudden onset and early stabilization of neurological signs, multiple horses affected, recent fever, respiratory disease, abortion.<ref>Wilson, W.D, Pusterla, N (2010) ''Equine Herpesvirus-1 Myeloencephalopathy'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Dysuria not often seen in EPM.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

|Sudden onset and early stabilization of neurological signs, multiple horses affected, recent fever, respiratory disease, abortion.<ref>Wilson, W.D, Pusterla, N (2010) ''Equine Herpesvirus-1 Myeloencephalopathy'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Dysuria not often seen in EPM.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

|CSF analysis, buffy coat, nasal swab PCR.<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref><ref name="Seino">Seino, K.K (2010) ''Spinal Ataxia'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 3.</ref>

|CSF analysis, buffy coat, nasal swab PCR.<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref><ref name="Seino">Seino, K.K (2010) ''Spinal Ataxia'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 3.</ref>

|-

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|Rabies

|[[Rabies]]

|Rapid progression<ref name="Sommardahl">Sommardahl, C.S (2010) ''Rabies'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>, behavioural alterations, depression, seizure, coma.<ref name="Long">Long, M.T (2010) ''Flavivirus Encephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  

|Rapid progression<ref name="Sommardahl">Sommardahl, C.S (2010) ''Rabies'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>, behavioural alterations, depression, seizure, coma.<ref name="Long">Long, M.T (2010) ''Flavivirus Encephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  

|Post-mortem fluorescent antibody testing of brain required for definitive diagnosis.<ref name="Sommardahl">Sommardahl, C.S (2010) ''Rabies'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  

|Post-mortem fluorescent antibody testing of brain required for definitive diagnosis.<ref name="Sommardahl">Sommardahl, C.S (2010) ''Rabies'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  

|CSF analysis and culture.  '''NB: CSF collection contraindicated if clinical signs suggest high intracranial pressure'''  

|CSF analysis and culture.  '''NB: CSF collection contraindicated if clinical signs suggest high intracranial pressure'''  

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|CNS abscessation due to 'bastard strangles'<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

|CNS abscessation due to [[Streptococcus equi subsp. equi|'bastard strangles]]'<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

|History of ''Streptococcus equi subsp. equi'' infection.<ref name="Byrne">Byrne, B. A (2010) ''Diseases of the Cerebellum'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

|History of [[Streptococcus equi subsp. equi|''Streptococcus equi subsp. equi'']] infection.<ref name="Byrne">Byrne, B. A (2010) ''Diseases of the Cerebellum'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

|CSF analysis (severe, suppurative inflammation), culture of CSF.<ref name="Byrne">Byrne, B. A (2010) ''Diseases of the Cerebellum'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

|CSF analysis (severe, suppurative inflammation), culture of CSF.<ref name="Byrne">Byrne, B. A (2010) ''Diseases of the Cerebellum'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

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NB: EPM has been seen concurrently with equine motor neuron disease in a mule<ref>Finno, C.J, Eaton, J.S, Aleman, M, Hollingsworth, S.R (2010) Equine protozoal myeloencephalitis due to ''Neospora hughesi'' and equine motor neuron disease in a mule.  ''Vet Ophthalmol'', 13(4):259-65.</ref>

NB: EPM has been seen concurrently with equine motor neuron disease in a mule<ref>Finno, C.J, Eaton, J.S, Aleman, M, Hollingsworth, S.R (2010) Equine protozoal myeloencephalitis due to ''Neospora hughesi'' and equine motor neuron disease in a mule.  ''Vet Ophthalmol'', 13(4):259-65.</ref>

[[Image:Equine_Protozoal_Myeloencephalitis.jpg|600px|thumb|left|''' Sarcocystis neurona stages and lesions.  

[[Image:Equine_Protozoal_Myeloencephalitis.jpg|600px|thumb|right|''' Sarcocystis neurona stages and lesions.  

(A). Cross section of spinal cord of horse with focal areas of discoloration (arrows) indicative of necrosis. Unstained.  

(A). Cross section of spinal cord of horse with focal areas of discoloration (arrows) indicative of necrosis. Unstained.  

The Food and Drug Administration (FDA) has approved four treatments for use in horses with EPM, but not all of these are commercially available:<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>

The Food and Drug Administration (FDA) has approved four treatments for use in horses with EPM, but not all of these are commercially available:<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>

*'''Sulfadiazine and pyrimethamine combination, ('Rebalance™', Antiprotozoal Oral Suspension, IVX Animal Health)''': administered PO daily for a minimum of 90 days. Due to availability and ease of administration, some use an off-label regimen of trimethoprimsulfa tablets with pyrimethamine tablets.  Pyrimethamine must be given at least 1 hr before or after hay is fed.(Merck)  ''Mode of action'': trimethoprim, sulfadiazine, and pyrimethamine all inhibit enzymes of folic acid synthesis.  ''Efficacy'': 61.5% improvement by one clinical grade.<ref name="MacKay">MacKay, R.J (2006) Equine protozoa myeloencephalitis: treatment, prognosis and prevention.  ''Clin Tech Equine Pract'', 5:9-16.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>''Potential adverse effects'': bone marrow suppression (mild anaemia, leucopenia, neutropenia, thrombocytopenia), fever, anorexia, depression, acute worsening of ataxiam altered reproductive performance in stallions<ref>Bedford, S.J, McDonnell, S.M (1999) Measurements of reproductive function in stallions treated with trimethoprim-sulfamethoxazole and pyrimethamine. ''J Am Vet Med Assoc'', 215:1317–1319.  In: Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>, congenital defects<ref>Toribio, R.E, Bain, F.T, Mrad, D.R, Messer, N.T, Sellers, R.S, Hinchcliff, K.W (1998) Congenital defects in newborn foals of mares treated for equine protozoal myeloencephalitis during pregnancy. ''J Am Vet Med Assoc'', 212:697–701.  In: Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>and abortion.  Folic acid deficiency may also cause gastrointestinal disturbances such as glossitis.<ref>Piercy, R.J, Hinchcliff, K.W, Reed, S.M (2002) Folate deficiency during treatment with orally administered folic acid, sulphadiazine and pyrimethamine in a horse with suspected equine protozoal myeloencephalitis (EPM). ''Equine Vet J'', 34:311–316.  In: Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>Blood dyscrazias are typically self-limiting and resolve on withdrawal of treatment.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Feeding high quantities of green forage should reduce the risk of anaemia after prolonged treatment.(MErck)

*'''Sulfadiazine and pyrimethamine combination, ('Rebalance™', Antiprotozoal Oral Suspension, IVX Animal Health)''': administered PO daily for a minimum of 90 days. Due to availability and ease of administration, some use an off-label regimen of trimethoprimsulfa tablets with pyrimethamine tablets.  Pyrimethamine must be given at least 1 hr before or after hay is fed.<ref name="Merck">Merck & Co (2008) The Merck Veterinary Manual (Eighth Edition), Merial</ref> ''Mode of action'': trimethoprim, sulfadiazine, and pyrimethamine all inhibit enzymes of folic acid synthesis.  ''Efficacy'': 61.5% improvement by one clinical grade.<ref name="MacKay">MacKay, R.J (2006) Equine protozoa myeloencephalitis: treatment, prognosis and prevention.  ''Clin Tech Equine Pract'', 5:9-16.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>''Potential adverse effects'': bone marrow suppression (mild anaemia, leucopenia, neutropenia, thrombocytopenia), fever, anorexia, depression, acute worsening of ataxia and altered reproductive performance in stallions<ref>Bedford, S.J, McDonnell, S.M (1999) Measurements of reproductive function in stallions treated with trimethoprim-sulfamethoxazole and pyrimethamine. ''J Am Vet Med Assoc'', 215:1317–1319.  In: Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>, congenital defects<ref>Toribio, R.E, Bain, F.T, Mrad, D.R, Messer, N.T, Sellers, R.S, Hinchcliff, K.W (1998) Congenital defects in newborn foals of mares treated for equine protozoal myeloencephalitis during pregnancy. ''J Am Vet Med Assoc'', 212:697–701.  In: Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>and abortion.  Folic acid deficiency may also cause gastrointestinal disturbances such as glossitis.<ref>Piercy, R.J, Hinchcliff, K.W, Reed, S.M (2002) Folate deficiency during treatment with orally administered folic acid, sulphadiazine and pyrimethamine in a horse with suspected equine protozoal myeloencephalitis (EPM). ''Equine Vet J'', 34:311–316.  In: Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>Blood dyscrazias are typically self-limiting and resolve on withdrawal of treatment.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Feeding high quantities of green forage should reduce the risk of anaemia after prolonged treatment. <ref name="Merck">Merck & Co (2008) The Merck Veterinary Manual (Eighth Edition), Merial</ref>

*'''Ponazuril (Marquis®, Bayer Animal Health)''': PO daily for 28 days, use in pregnant animals is off-label.  ''Mode of action'': ponazuril is a triazinetrione that targets the “apicoplast” organelle and inhibits the respiratory chain.  ''Efficacy'': well absorbed PO, achieves steady state therapeutic concentration in CSF within 3 days<ref>Furr, M, Kennedy, T (2001) Cerebrospinal fluid and serum concentrations of ponazuril in horses.  ''Vet Ther'', 2:232-237.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>clinical response within 10 days, 60% improvement by at least one clinical grade, 8% relapse within 90 days of stopping treatment.<ref>Furr, M, Kennedy, T, MacKay, R, Reed, S, Andrews, F, Bernard, B, Bain, F, Byars, D (2001) Efficacy of ponazuril 15% oral paste as a treatment for equine protozoal myeloencephalitis. ''J Vet Ther'', 2:215-222.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  ''Potential adverse effects'': none in a multi-centre field study<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>, no systemic toxicity even at high doses.<ref>Kennedy, T, Campbell, J, Selzer, V (2001) Safety of ponazuril 15% oral paste in horses.  ''Vet Ther'', 2:223-231.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>However, the manufacturer reports signs that may have been related to treatment including blisters on nose and mouth, skin rash or hives, loose stools, mild colic, and a seizure.<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>

*'''Ponazuril (Marquis®, Bayer Animal Health)''': PO daily for 28 days, use in pregnant animals is off-label.  ''Mode of action'': ponazuril is a triazinetrione that targets the “apicoplast” organelle and inhibits the respiratory chain.  ''Efficacy'': well absorbed PO, achieves steady state therapeutic concentration in CSF within 3 days<ref>Furr, M, Kennedy, T (2001) Cerebrospinal fluid and serum concentrations of ponazuril in horses.  ''Vet Ther'', 2:232-237.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>clinical response within 10 days, 60% improvement by at least one clinical grade, 8% relapse within 90 days of stopping treatment.<ref>Furr, M, Kennedy, T, MacKay, R, Reed, S, Andrews, F, Bernard, B, Bain, F, Byars, D (2001) Efficacy of ponazuril 15% oral paste as a treatment for equine protozoal myeloencephalitis. ''J Vet Ther'', 2:215-222.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  ''Potential adverse effects'': none in a multi-centre field study<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>, no systemic toxicity even at high doses.<ref>Kennedy, T, Campbell, J, Selzer, V (2001) Safety of ponazuril 15% oral paste in horses.  ''Vet Ther'', 2:223-231.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>However, the manufacturer reports signs that may have been related to treatment including blisters on the nose and mouth, skin rash or hives, loose stools, mild colic, and a seizure.<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>

*'''Diclazuril''': PO, daily for 28 days, approved by FDA for use as top-dress tablet but not commercially available ''Mode of action'': chemically similar to ponazuril but mechanism of action unknown.  ''Efficacy'': one study reported clinical improvement in 58% of cases.<ref name="MacKay">MacKay, R.J (2006) Equine protozoa myeloencephalitis: treatment, prognosis and prevention.  ''Clin Tech Equine Pract'', 5:9-16.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  ''Potential adverse effects'': none found in one efficacy study.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Reported problems in a multi-centre field study included worsening neurologic status and laminitis but these were not proven to be related to treatment.<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>

*'''Diclazuril''': PO, daily for 28 days, approved by FDA for use as top-dress tablet but not commercially available.  ''Mode of action'': chemically similar to ponazuril but mechanism of action unknown.  ''Efficacy'': one study reported clinical improvement in 58% of cases.<ref name="MacKay">MacKay, R.J (2006) Equine protozoa myeloencephalitis: treatment, prognosis and prevention.  ''Clin Tech Equine Pract'', 5:9-16.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  ''Potential adverse effects'': none found in one efficacy study.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Reported problems in a multi-centre field study included worsening neurologic status and laminitis but these were not proven to be related to treatment.<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>

*'''Nitazoxanide, NTZ ('Navigator®', Idexx Pharmaceuticals)''': no longer commercially available in the US.  ''Mode of action'': a member of the 5-nitrothiazole class of antiparasitics that inhibits the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme dependent electron transfer reaction essential for anaerobic energy metabolism.<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>  ''Efficacy'': 60% success rate in an FDA-regulated study.<ref name="MacKay">MacKay, R.J (2006) Equine protozoa myeloencephalitis: treatment, prognosis and prevention.  ''Clin Tech Equine Pract'', 5:9-16.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref> ''Potential adverse effects'': adverse effects and death at high doses<ref name="MacKay">MacKay, R.J (2006) Equine protozoa myeloencephalitis: treatment, prognosis and prevention.  ''Clin Tech Equine Pract'', 5:9-16.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>, fever, anorexia, diarrhoea, lethargy, depression and laminitis recorded at lower doses.  Toxic signs usally resolve upon cessation of treatment.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  '''''Caution: 'administration of nitazoxanide can disrupt the normal microbial flora of the gastrointestinal tract leading to enterocolitis.  Deaths due to enterocolitis have been observed while administering the recommended dose in field studies.'''''<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>

*'''Nitazoxanide, NTZ ('Navigator®', Idexx Pharmaceuticals)''': no longer commercially available in the US.  ''Mode of action'': a member of the 5-nitrothiazole class of antiparasitics that inhibits the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme dependent electron transfer reaction essential for anaerobic energy metabolism.<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>  ''Efficacy'': 60% success rate in an FDA-regulated study.<ref name="MacKay">MacKay, R.J (2006) Equine protozoa myeloencephalitis: treatment, prognosis and prevention.  ''Clin Tech Equine Pract'', 5:9-16.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref> ''Potential adverse effects'': adverse effects and death at high doses<ref name="MacKay">MacKay, R.J (2006) Equine protozoa myeloencephalitis: treatment, prognosis and prevention.  ''Clin Tech Equine Pract'', 5:9-16.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>, fever, anorexia, diarrhoea, lethargy, depression and laminitis recorded at lower doses.  Toxic signs usally resolve upon cessation of treatment.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  '''''Caution: 'administration of nitazoxanide can disrupt the normal microbial flora of the gastrointestinal tract leading to enterocolitis.  Deaths due to enterocolitis have been observed while administering the recommended dose in field studies.'''''<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>

Prolonged, off-license treatment is often instigated after 1 month, based on repeated clinical examination.  Even successfully treated cases may remain immunoblot positive for long periods, thus aiming for seronegativity is unrealistic.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  A lack of response to treatment suggests that the diagnosis should be re-assessed.  Another month's worth of the same treatment is recommended for partial responders, switching to a different chemical class if this fails.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref> The efficacy of currently approved antiprotozoals against ''N.hughesi'' is unknown.(Furr)

Prolonged, off-license treatment is often instigated after 1 month, based on repeated clinical examination.  Even successfully treated cases may remain immunoblot positive for long periods, thus aiming for seronegativity is unrealistic.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  A lack of response to treatment suggests that the diagnosis should be re-assessed.  Another month's worth of the same treatment is recommended for partial responders, with switching to a different chemical class if this fails.  The efficacy of currently approved antiprotozoals against ''N.hughesi'' is unknown.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

===Ancillary medication===

===Ancillary medication===

*'''NSAIDs''': DMSO IV as 10% solution, thought to reduce CSF pressure and improve clinical status.  Recommended for severe cases of EPM or to avoid worsening inflammation that may be induced by parasite kill.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Caution: DMSO may cause intravascular haemolysis.<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>

*'''NSAIDs''': DMSO IV as 10% solution, thought to reduce CSF pressure and improve clinical status.  Recommended for severe cases of EPM or to avoid worsening inflammation that may be induced by parasite kill.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Caution: DMSO may cause intravascular haemolysis.<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>

*'''Corticosteroids''': a short course of dexamethasone may be beneficial whilst waiting for antiprotozoals to take effect.  However, use is controversial because cell-mediated immunity is required to control parasites<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref> and stress is a proposed risk factor for EPM.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

*'''Corticosteroids''': a short course of dexamethasone may be beneficial whilst waiting for antiprotozoals to take effect.  However, use is controversial because cell-mediated immunity is required to control parasites<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref> and stress is a proposed risk factor for EPM.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

*'''Immunomodulators''': '''Levamisole''' influences T-cell mediated immunity and enhances phagocytosis.  '''Parapox ovis virus (PPOV)''' immunomodulator (Zylexis, Pfizer Animal Health, Kalamazoo, Mich).  This vaccine has been shown to upregulate the secretion of cytokines including IFN-γ in several species.<ref>Frieb, A, Siegling, A, Friederichs, S, Volk, H-D, Weber, O (2004) Effects of inactivated parapoxvirus ovis (orf virus) on human peripheral immune cells: induction of cytokine secretion in monocytes and Th1-like cells.  ''J Virol'', 78:9400-9411.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>IFN-γ is thought to be essential for the clearance of S neurona, thus PPOV may be useful in EPM.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

*'''Immunomodulators''': '''Levamisole''' influences T-cell mediated immunity and enhances phagocytosis.  '''Parapox ovis virus (PPOV)''' immunomodulator (Zylexis, Pfizer Animal Health, Kalamazoo, Mich).  This vaccine has been shown to upregulate the secretion of cytokines including IFN-γ in several species.<ref>Frieb, A, Siegling, A, Friederichs, S, Volk, H-D, Weber, O (2004) Effects of inactivated parapoxvirus ovis (orf virus) on human peripheral immune cells: induction of cytokine secretion in monocytes and Th1-like cells.  ''J Virol'', 78:9400-9411.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>IFN-γ is thought to be essential for the clearance of ''S.neurona'', thus PPOV may be useful in EPM.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

*'''Multiple vitamin B supplement'''.<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>

*'''Multiple vitamin B supplement'''.<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>

==Prognosis==

==Prognosis==

Depends on duration and severity of neurological signs<ref name="EPM3">Vatistas, N, Mayhew, J (1995) Differential diagnosis of polyneuritis equi.  ''In Practice'', Jan, 26-29.</ref> but clinical resolution is more likely if the condition is diagnosed and treated early.<ref name="EPM8">Gray, L.C, Magdesian, K.G, Sturges, B.K, Madigan, J.E (2001) Suspected protozoal myeloencephalitis in a two-month-old colt.  ''Vet Record'', 149:269-273.</ref>    With standard therapy, involving 6-8months of ponazuzril or pyrimethamine-sulfadiazine (V), there is a recovery rate of around 25% and an improvement in 60-75% of cases.<ref name="MacKay">MacKay, R.J (2006) Equine protozoa myeloencephalitis: treatment, prognosis and prevention.  ''Clin Tech Equine Pract'', 5:9-16.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref> A good prognosis might be expected if there is an improvement in clinical signs within two weeks of commencing anti-protozoal and anti-inflammatory treatment (V).  The prognosis will be guarded to poor<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref> for a horse with severe irreversible neuronal damage or one that has not been diagnosed or treated appropriately (V).

Depends on duration and severity of neurological signs<ref name="EPM3">Vatistas, N, Mayhew, J (1995) Differential diagnosis of polyneuritis equi.  ''In Practice'', Jan, 26-29.</ref> but clinical resolution is more likely if the condition is diagnosed and treated early.<ref name="EPM8">Gray, L.C, Magdesian, K.G, Sturges, B.K, Madigan, J.E (2001) Suspected protozoal myeloencephalitis in a two-month-old colt.  ''Vet Record'', 149:269-273.</ref>    With standard therapy, there is a recovery rate of around 25% and an improvement in 60-75% of cases.<ref name="MacKay">MacKay, R.J (2006) Equine protozoa myeloencephalitis: treatment, prognosis and prevention.  ''Clin Tech Equine Pract'', 5:9-16.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref> A good prognosis might be expected if there is a response to treatment within two weeks.  The prognosis will be guarded to poor<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref> for a horse with severe, irreversible neuronal damage.

==Prevention==

==Prevention==

===Prophylaxis===

===Prophylaxis===

A killed vaccine, developed using ''S.neurona'' merozoites, was conditionally licensed for use in horses.<ref>Saville, W.J.A, Reed, S.M, Dubey, J.P (2002) Prevention of equine protozoal myeloencephalitis(EPM). ''Proceedings of the Annual Convention of the AAEP'', 48:181-185.</ref>  The vaccine proved to be ineffective in the prevention of EPM and has since been removed from the market.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  There is evidence to suggest that the antiprotozoal, ponazuril, may be useful prophylactically to reduce the incidence and severity of clinical signs.<ref>Furr, M, MacKenzie, H, Dubey, J.P (2006) Pretreatment of horses with ponazuril limits infection and neurologic signs resulting from S.neurona.  ''J Parasitol'', 92:637-643.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Implementing such a regime prior to and during stressful events may be beneficial, although the cost is likely to be prohibitive.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>Protocols involving intermittent administration of ponazuril may also show promise in the prevention of EPM.<ref>Mackay, R.J, Tanhauser, S.T, Gillis, K.D, Mayhew, I.G, Kennedy, T.J (2008) Effect of intermittent oral administration of ponazuril on experimental ''Sarcocystis neurona'' infection of horses.  ''Am J Vet Res'', 69(3):396-402.</ref>

A killed vaccine, developed using ''S.neurona'' merozoites, was conditionally licensed for use in horses.<ref name="Saville1">Saville, W.J.A, Reed, S.M, Dubey, J.P (2002) Prevention of equine protozoal myeloencephalitis(EPM). ''Proceedings of the Annual Convention of the AAEP'', 48:181-185.</ref>  The vaccine proved to be ineffective in the prevention of EPM and has since been removed from the market.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  There is evidence to suggest that the antiprotozoal, ponazuril, may be useful prophylactically to reduce the incidence and severity of clinical signs.<ref>Furr, M, MacKenzie, H, Dubey, J.P (2006) Pretreatment of horses with ponazuril limits infection and neurologic signs resulting from S.neurona.  ''J Parasitol'', 92:637-643.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Implementing such a regime prior to and during stressful events may be beneficial, although the cost is likely to be prohibitive.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>Protocols involving intermittent administration of ponazuril may also show promise in the prevention of EPM.<ref>Mackay, R.J, Tanhauser, S.T, Gillis, K.D, Mayhew, I.G, Kennedy, T.J (2008) Effect of intermittent oral administration of ponazuril on experimental ''Sarcocystis neurona'' infection of horses.  ''Am J Vet Res'', 69(3):396-402.</ref>

 

 

 

 

 

==References==

==References==

[[Category:Tissue_Cyst_Forming_Coccidia]][[Category:Horse]]

[[Category:Expert_Review]]

[[Category:To_Do_-_Nina]]

[[Category:Neurological Diseases - Horse]]