WikiVet English

Equine Protozoal Myeloencephalitis

Revision as of 11:17, 20 July 2010 by Nmr28 (talk | contribs) (→‎Treatment)



 This article is still under construction.



Also known as: EPM

Equine protozoal myelitis
 Equine protozoal encephalomyelitis


Description

A progressive, infectious,[1]neurological disease of horses, endemic in the USA[2] and only encountered elsewhere in imported equids.[3] EPM is one of the most frequently diagnosed neurological conditions of the Western Hemisphere[4] and the principal differential for multifocal, asymmetric progressive central nervous system (CNS) disease.[1] As it can resemble any neurological disorder, EPM must be considered in any horse with neurological signs if it resides in the Americas or if it has been imported from that area[2][5] The disease is not contagious.[1]

Aetiology

EPM results from infection of the CNS by the apicomplexan parasite Sarcocystis neurona or, less frequently, its close relative Neospora hughesi.[6][7] These protozoans develop within neurons[4] 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.[1]

Epidemiology

In endemic areas of the United States, around a quarter of referrals for equine neurological disease are attributed to EPM.[8] According to the United States Department of Agriculture, the average incidence of the disease is 14 cases per 10,000 horses per year. However, the challenges of obtaining a definitive diagnosis may mean this figure is an underestimate.[4] The disease has been identified in parts of Central and South America, southern Canada and across most of the USA..[4] EPM is noted occasionally in other countries, in horses that have been imported from the Americas.[9][10] It is likely that these animals underwent transportation carrying a silent but persistent infection. There have been reports of EPM in horses that have not travelled to or from endemic regions,[4] although cross-reacting antigens on the immunoblot test may explain this discrepancy. [4]

The route of infection remains unconfirmed,[1] but there is an increased risk associated with a young age (1-4 years)[11]and autumn months.[12] The reported age range for EPM cases is currently 2 months[2] to 24 years.[13] Thoroughbreds, Standardbreds and Quarterhorses are most frequently affected across the US and Canada.[14] This may relate to a breed predispostion or alternatively, managemental factors associated with these breeds.[15] Showing, racing and stress[16] have been linked to a greater risk of clinical disease.[17]

Increasing age and environmental temperature have been associated with an increased seroprevalence of S. neurona.[18] Seroprevalence for this species is typically higher than for N. hughesi.[4]Other risk factors for EPM include the presence of opossums, rats, mice and woodland, increased population density of humans and horses, bedding horses on shavings or wood chips and the use of purchased grain.[4]Case clustering may operate where all the risk factors occur, but the majority of cases appear in isolation.[4]

Life Cycle

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.

See here for further details of the life cycle of Sarcocystis neurona.

The causative pathogen(s) have been isolated from species other than the horse including zebra, domestic cat, Canadian lynx, sea otter, straw-necked ibis, mink, raccoon and sunk. (Furr)

Signalment

Mostly Standardbreds and Thoroughbreds aged 1-6years.[1] Foal infection may be possible.[2]

Clinical Signs

The disease onset may be acute, peracute or chronic. An insidious onset ataxia is most typical and with such cases, the clinical examination may reveal a bright, alert horse, perhaps with some focal muscle atrophy.[4] In all cases, the clinical signs are referable to diffuse focal and multifocal lesions of the white and grey matter of the spinal cord and brain.[3] The three characteristic 'As' (ataxia, asymmetry, atrophy) suggest multifocal or diffuse disease, but are not pathognomonic for EPM.[4]

Lesion Location Clinical signs
Spinal cord
  • Ataxia, paresis or spasticity of one or more limbs, often asymmetrical, signs usually worse in hindlimbs, may see stumbling, falling, knuckling, toe dragging, circumduction, crossing over, tetraparesis - areflexia, hyporeflexia (LMN) or hyperreflexia (UMN) depending on site of lesion
  • Loss of reflexes or cutaneous anaesthesia
  • Apparent lameness, particularly atypical or slight gait asymmetry of hindlimbs (not alleviated by local anaesthesia)
  • Abnormal placing reactions
  • Focal muscle atrophy of individual muscle groups[1], especially gluteal muscles, often asymmetrical
  • Generalized muscle atrophy or loss of condition
  • Localized sensory deficits and 'strip sweating' of dermatomes
  • Sacrococcygeal involvement will produce signs that mimic polyneuritis equi
Peripheral nerves
  • Upward fixation of the patella
  • Exertional rhabdomyolysis
  • Back pain
  • Gait abnormality
Brainstem (cranial nerve signs)
  • Atrophy of temporalis and masseter muscles, loss of facial sensation (V)
  • Facial (VII) and vestibulocochlear (VIII) nerve deficits often seen together:
    • VIII - vestibular signs: nystagmus, head tilt, base-wide stance (peripheral or central vestibular disease)
    • VII - unilateral facial paralysis: muzzle deviation, ptosis, ear droop
  • Loss of tongue tone (XII)
  • Dysphagia (V, VII, IX, X, XII)
  • Dorsal displacement of the soft palate (IX, X)
  • Laryngeal hemiplegia (X)
  • Abnormal menace response (II, VII)
  • Headshaking[19]
  • Blindness with or without abnormal pupillary reflexes,[1]
Cerebrum, basal nuclei, cerebellum
  • Abnormal menace response
  • Circling
  • Seizures (may be the only clinical sign)[20]
  • Abnormal electroencephalogram (EEG)
  • Asymmetrical central blindness
  • Facial hypoalgesia
  • Cerebellar ataxia
  • Altered behavior
  • Depression
  • Narcolepsy-like syndrome

Lesions of the brainstem, cerebrum or cerebellum are less frequently recognized than those of the spinal cord. Horses with severe EPM may be unable to stand or swallow and, if left untreated, progress to recumbency within 14 days to 6 months.[1] This deterioration may occur smoothly or spasmodically,[21] but is likely to result in death. It has been suggested that rapidly progressive presentations reflect brainstem lesions.[4]

Diagnosis

Differential Diagnoses

The protozoan can migrate to any region of the CNS[2], thus the differential list comprises almost all diseases of this system.

Differential Differentiating signs Tests to rule out
Cervical vertebral malformation (CVM, cervical compressive myelopathy, cervical vertebral instability, cervical stenotic myelopathy, cervical spondylomyelopathy, Wobbler's syndrome). Symmetrical gait deficits, worse in pelvic limbs[22] with spasticity and dysmetria, good retention of strength, no muscle wasting.[4] NB: can be concurrent with EPM.[23] Plain lateral radiography of C1 to T1[23], myelography. [24]
West Nile encephalitis Systemically ill, pyrexia. Difficult to differentiate if horse is afebrile and has no excessive muscle fasciculations.[25] Leukogram, CSF analysis, IgM capture ELISA, plaque reduction neutralization test (PRNT),[24]absence of mosquito vectors.[26]
WEE Systemically ill, pyrexia, abnormal motor function.[25] Leukogram, ELISA, titres, virus isolation.[24]
EEE Systemically ill, pyrexia, abnormal motor function[25], rapidly progressive.[24] Leukogram, CSF analysis, ELISA, titres, virus isolation.[24]
VEE Systemically ill, pyrexia. Leukogram, IgM ELISA[27]
Equine herpesvirus-1 myeloencephalopathy Sudden onset and early stabilization of neurological signs, multiple horses affected, recent fever, respiratory disease, abortion.[28] Dysuria not often seen in EPM.[4] CSF analysis, buffy coat, nasal swab PCR.[26][24]
Rabies Rapid progression[29], behavioural alterations, depression, seizure, coma.[25] Post-mortem fluorescent antibody testing of brain required for definitive diagnosis.[29]
Polyneuritis equi (previously cauda equina neuritis) Cranial nerve deficits are peripheral with no change in attitude.[30] Western blot analysis of CSF.[31]
Equine degenerative myeloencephalopathy Symmetrical signs.[32] May get increased CSF creatinine kinase (CK)[33] and reduced serum Vitamin E concentrations but these are unreliable for ante mortem diagnosis.[32]
Verminous encephalomyelitis Acute onset. CSF analysis.[34]
Bacterial meningoencephalitis Stiff neck.[1]
CNS abscessation due to 'bastard strangles'[4] History of Streptococcus equi subsp. equi infection.[35] CSF analysis (severe, suppurative inflammation), culture of CSF.[35]
Spinal trauma[1] History (usually acute onset neurological signs), usually solitary lesion localised by neurological exam.[36] Radiography, myelography, CT, MRI, nuclear scintigraphy, ultrasound, CSF analysis, nerve conduction velocities, EMG, transcranial magnetic stimulation.[37]
Occipito-atlanto-axial malformation (OAAM) Deficits develop before 6mths in Arabian horse.[38] Radiography.[24]
Spinal tumor Signs can usually be localized to one region of the CNS. CT, MRI. Definitive diagnosis requires cytology, biopsy, histopathology or CSF analysis.[39]
Sorghum cystitis/ataxia[1] Posterior ataxia or paresis, cystitis, history of grazing Sorghum species[40] Demonstration of cystitis or pyelonephritis by laboratory methods, but not specific.[41]
Sarcocystis neurona stages and lesions. (A). Cross section of spinal cord of horse with focal areas of discoloration (arrows) indicative of necrosis. Unstained. (B). Section of spinal cord of a horse with severe EPM. Necrosis, and a heavily infected neuron (arrows), all dots (arrows) are merozoites. H and E stain . (C). Higher magnification of a dendrite with numerous merozoites (arrows). One extracellular merozoite (arrowhead) and a young schizont (double arrowhead). (D). Section of brain of an experimentally-infected mouse stained with anti-S. neurona antibodies. Note numerous merozoites (arrows). (E). Immature schizonts in cell culture. A schizont with multilobed nucleus (arrow) and a schizont with differentiating merozoites (arrowheads). Giemsa stain. (F). Mature sarcocysts with hairlike villar protrusions (double arrowheads) on the sarcocyst wall. H and E stain. (G). Mature live sarcocyst with numerous septa (arrows) and hairlike protrusions on the sarcocyst wall (double arrowheads). Unstained. (H). An oocyst with two sporocysts each with banana-shaped sporozoites. Unstained. 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.

Pathology

Widespread lesions of the CNS are typically observed in horses.[4]

Gross exam

Lesions may be up to several centimetres across.[4] They range from mild discolouration to multifocal areas of haemorrhage and/or malacia[21] of the brain, spinal cord and less commonly, peripheral nerves.[4]

Histopathology

Microscopically, both grey and white matter may be affected with focal to diffuse areas of nonsuppurative inflammation, necrosis and neuronal destruction. Perivascular infiltrates comprise lymphocytes, macrophages, plasma cells, giant cells, eosinophils and gitter cells.[4] In around 25% of cases, schizonts or merozoites may be found in the neuronal cytoplasm.[21] Less frequently, protozoa parasitize intravascular and tissue neutrophils and eosinophils, capillary endothelial cells and myelinated axons[4][21]. Free merozoites may be seen in necrotic regions. If organisms are absent, the diagnosis relies on recognition of the inflammatory changes described above.[21]

Treatment

Antiprotozoals

Treatment is also challenging, because several medications are available and response to treatment is not consistent among horses. There are four treatments currently approved by the Food and Drug Administration (FDA) for EPM, but only three have been commercially available: a sulfadiazine and pyrimethamine combination, ponazuril, and nitazoxanide. Diclazuril has been approved but not yet marketed. Recently (spring of 2009), the commercially available form of nitazoxanidea has been discontinued.

The FDA-approved combination is sulfadiazine and pyrimethamineb daily for a minimum of 90 days. If the FDA-approved combination is unavailable, some practitioners opt to use trimethoprimsulfa tablets q 12–24 h, PO) with pyrimethamine tablets (q 24 h, PO) because of availability or ease of administration. However, this regimen constitutes extra-label/unapproved use. All three of the drugs (trimethoprim, sulfadiazine, and pyrimethamine) inhibit enzymes in the folic acid pathway and thereby, inhibit thymidine synthesis. The most common adverse reaction in one study was bone marrow suppression (anemia, leucopenia, neutropenia, and/or thrombocytopenia) . Adverse effects attributed to treatment included fever, leucopenia, anorexia, depression, acute worsening of ataxia, mild anemia, and abortions. In addition to blood dyscrasias, folic acid deficiency may lead to gastrointestinal disturbances such as glossitis.18 Stallions treated for 90 days with trimethoprim-sulfamethoxazole and pyrimethamine may have changes in copulatory form and agility along with altered pattern and strength of ejaculation.19 Three mares receiving sulfonamides, pyrimethamine (with or without trimethoprim), and folic acid delivered foals with congenital defects that died or were euthanized.20(IVIS 4) Sulphonamide drugs combined with pyrimethamine for synergism - FDA approved Sulfadiazine and pyriemthamine PO SID 'Re-Balance' no longer available? - 61.5% improvement by one clinical grade, tx for 90-270days (98 in frr) Complications: anaemia, leukopenia, neutropenia (98 in furr) - usually self limiting, resolve with cessation of tx Use of sulfadizine in breeding animals controversial but one study showed no effect on pregnancy rates or EED Sulfamethoxazole and pyrimethamine caused mild ataxia associated with mounting and ejaculation in a grp of pony stallions (99 in furr)

Ponazuril (Marquis, Bayer Animal Health) - 1st FDA-approved drug for EPM, well absorbed PO, achieves steady state therapeutic concentration in 3days in CSF of horses (100 in Furr). In filed efficacy study improvement bny at least one clincal gradein 60%, 8% relase after 90days of stopping treatment (91 in Furr), resposne wihtin 10days. V safe, no sstemci toxicity even at high doses (101 in Furr), use in pregannt animals is off-label, feeding corn oil immediately prior to admin may enahcne absrobption of durg (103 in Furr) Ponazuril is a triazinetrione antiprotozoal drug that targets the “apicoplast” organelle and inhibits energy metabolism (respiratory chains). The label dosage regimen PO daily for 28 days. A multi-center field study - no adverse effects were noted. However, information provided by the manufacturer reports “unusual daily observations” in eight animals that may have been related to treatment including blisters on nose and mouth, skin rash or hives, loose stools, mild colic, and a seizure.(IVIS 4) Protocols involving intermittent administration of ponazuril may have application in prevention of EPM. (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. Treatment with ponazuril minimizes, but does not eliminate, infection and clinical signs of EPM in horses. (Furr, M, McKenzie, H, Saville, W.J, Dubey, J.P, Reed, S.M, Davis, W (2006) Prophylactic administration of ponazuril reduces clinical signs and delays seroconversion in horses challenged with Sarcocystis neurona. J Parasitol, 92(3):637-43.

Diclazuril po, SID, chemically similar to ponazuril, one study imorvment in 58% cases if gven for 28days (98 in Furr), approved by FDA for use as top-dress tablet but not comemrically avialable, no adverse effects in effciacy study.(Furr) Diclazuril is a triazinetrione antiprotozoal agent similar to ponazuril with an unknown (but possibly similar) mechanism of action. A multi-center clinical field study was performed. Reported adverse reactions were not clearly linked to drug administration and included worsening neurologic status and laminitis. Results of efficacy studies were surprisingly similar for each of the four approved therapies when similar methodologies and means of assessing improvement were used. Regardless of drug, _60% of treated horses improved by at least one neurologic grade or became negative on CSF WB. Based on reported side effects, ponazuril and diclazuril seem to have the fewest reported adverse effects. (IVIS 4)

NTZ (Navigator, Idexx Pharmaceuticals) member of 5-notrothiazol class of antimicrobials ad currently approved for tx of EPM, succes rate of about 60% in FDA-regulated study (98 in Furr). Adverse effects and death at high doses (98),, diarrhoea, depressiona and lamninits recorded at lower doses. {Poor completion rate and study compliance sugegts unreproted toxicity. Toxci signs usally resolve oin withdrawl of tx, no longer availbale in US. Even successfully treaed cases may remian immunoblot positive for long periods so trying ot treat unitl seronegatvie not relasiitc. Triaxine based rugs (ponazuril, diclazruil, NTZ) licensed to be used oinly for 28days. Longer tx often needed as determined by repeat exam after 1mth. No reposnee sugegsts misdx and case should be re-evaluated. If some resposne bt rmeiansabnromal, continue tx for another mth.(Furr) Paste no longer commercially available. This drug is a 5-nitrothiazole antiparasitic drug that inhibits the pyruvate:ferredoxin oxidoreductase (PFOR) enzymedependent electron transfer reaction essential for anaerobic energy metabolism. Reported side effects in these studies included inappetence and depression. Two field studies for efficacy and safety were conducted during the approval process for nitazoxanide. The most common adverse reactions were fever, anorexia/reduced appetite, and lethargy/depression. Following warning: “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.”a(IVIS 4)

Relapse rate u to 25% with sulfadiazien and pyrimethamine reporetd (104). Relpases should be treated wth same drug for longer period, authoir recommmnds 2mths ponaxuril then min 90 days sulfadiaizen -pyrimethamine. Failure of longher ocurse of ponazuril prmpts swewitch to diffeent chemical class (furr)

Dirikolu, L, Lehner, A.F, Hughes, C, Karpiesiuk, W, Tobin, T () New therapeutic approaches to equine protozoal myeloencephalitis: pharmacokinetcis of toltrazuril sulfone sodium salt in the horse

We had earlier identified triazine-based antiprotozoal agents for the treatment and prophylaxis of EPM, and on this basis, we elected to develop a highly bioavailable oral formulation, namely toltrazuril sulfone sodium salt (TSSS), that can be used for the treatment and prophylaxis of EPM. Based on these data, repeated oral-mucosal administration of TSSS with or without feed will yield useful steady-state plasma and cerebrospinal fluid concentrations of toltrazuril sulfone for the treatment and prophylaxis of EPM. (IVIS)

The only FDA-approved treatments for EPM are ponazuril (PO, SID for 28 days) and nitazoxanide (PO, sid for 28 days), both as paste formulations. An alternative approach is the use of antifolate drugs, eg, sulfadiazine, or sulfamethoxazole (PO, sid-bid) in combination with pyrimethamine (PO, sid). The sulfonamide can be given with or without trimethoprim. Pyrimethamine must be given at least 1 hr before or after hay is fed. Treatment is usually continued for 6 months. Anaemia may develop after prolonged treatment with antifolate drugs and is best prevented by provision of high quantities of green forage. At least 60% of horses improve with treatment, but <25% recover completely. Relapses are common in horses that remain positive on immunoblot and rare in those that become negative. (Merck) Combo of antifolate drugs - trimethoprim sulfa (PO q12hrs, 4-8wks) plus pyrimethamine (Darapem(R) malaria drug) (PO q12h, 3 d then PO q24h 4-8wk), blood count every 2wk during therapy because may cause folate deficiency (leukopenia, thrombocytopenia & anaemia, rare) - discontinue and give folate, folate supplement - potential toxicity in mares, (Pasq)

No studies ahve been condicted to determine effectiveness of currently aspproved antiprotozoals vs N hughesi(Furr)

Ancillary medication

NSAIDs in severe cases or to avoid 'tx cirsis' where it is is prosped that parasite kill transiently worsens inflmamtrion

  • DMSO IV as 10% solition - may lower CSF prfessure and imporve clinical status

Cortcosteroids - use debated, concern over immunsupprressions and that stress is risk factor for ePM, short course ofdex may help stabilize patient until antiprotoxoals take effect Immunomodulators to boost immue resopsne: levemaisole influecnes t-cell mediated immunity and enahcnes pahgocytosis, parapox ovis virus immunomodulator (Zylexis, Pfizer Animal HEalth, Kalamazoo, Mich) intende dto aid in tx of EHV-1 and 4, an upregulate secretion of IFN-gamma (110) in number of species, believed to be ciritcal for clearnace of S neurona, inclsuion of PPOV vaccien in tx of EPM may be logical (Furr) NSAIDS, not steroids (because of need for cell mediated immunity to control parasites) DMSO IV to decrease inflammation in 5% dextrose - given without difficulty but causes intravsacular haemolysis so haemoglobinuria or haematuria, variable positive or negative response time - insurance require 6wk before euthanise, monitor CBC every 10-14d, folate inhibitors, can get pancytopenia, marked platelet drop, cut back dose, multiple B vitamin supplement, stall rest, Diclazuril & Toltrazuril: antiprotozoal disease, need testing, euthanize if don't respond. (Pasq)

Supportive management

Stall with deep bedding and good footing for v ataxic animasl, turnout in leve grassy fueld with no obstacles, care re turnotu with herd matyes, recumebvnt animals need additional care (FUrr)

Prognosis

Depends on duration and severity of neurological signs[3] but clinical resolution is more likely if the condition is diagnosed and treated early.[2] 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.[42] 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[1] for a horse with severe irreversible neuronal damage or one that has not been diagnosed or treated appropriately (V).

Prevention

Prophylaxis

A killed vaccine, developed using S.neurona merozoites, was conditionally licensed for use in horses.[43] The vaccine proved to be ineffective in the prevention of EPM and has since been removed from the market.[4] There is evidence to suggest that the antiprotozoal, ponazuril, may be useful prophylactically to reduce the incidence and severity of clinical signs.[44] Implementing such a regime prior to and during stressful events may be beneficial, although the cost is likely to be prohibitive.[4]

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 Pasquini, C, Pasquini, S, Woods, P (2005) Guide to Equine Clinics Volume 1: Equine Medicine (Third edition), SUDZ Publishing, 245-250. Cite error: Invalid <ref> tag; name "Pasq" defined multiple times with different content Cite error: Invalid <ref> tag; name "Pasq" defined multiple times with different content Cite error: Invalid <ref> tag; name "Pasq" defined multiple times with different content Cite error: Invalid <ref> tag; name "Pasq" defined multiple times with different content Cite error: Invalid <ref> tag; name "Pasq" defined multiple times with different content Cite error: Invalid <ref> tag; name "Pasq" defined multiple times with different content Cite error: Invalid <ref> tag; name "Pasq" defined multiple times with different content Cite error: Invalid <ref> tag; name "Pasq" defined multiple times with different content Cite error: Invalid <ref> tag; name "Pasq" defined multiple times with different content Cite error: Invalid <ref> tag; name "Pasq" defined multiple times with different content Cite error: Invalid <ref> tag; name "Pasq" defined multiple times with different content
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 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. Cite error: Invalid <ref> tag; name "EPM8" defined multiple times with different content
  3. ↑ 3.0 3.1 3.2 Vatistas, N, Mayhew, J (1995) Differential diagnosis of polyneuritis equi. In Practice, Jan, 26-29.
  4. ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 4.16 4.17 4.18 4.19 4.20 4.21 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.
  5. ↑ DEFRA, The Animal Health Trust, The British Equine Veterinary Association (2009) Surveillance: Equine disease surveillance, April to June 2009, The Vet Rec, Oct 24:489-492.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ Reed, S.M, Granstrom, D, Rivas, L.J, Saville, W.A, Moore, B.R, Mitten, L.A (1994) Results of cerebrospinal fluid analysis in 119 horses testing positive to the Western blot test on both serum and CSF to equine protozoal encephalomyelitis. In Proc Am Assoc Equine Pract, Vancouver BC, AEEP, Lexington, KY, p199. 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.
  9. ↑ Pitel, P.H, Pronost, S, Gargala, G, Anrioud, D, Toquet, M-P, Foucher, N, Collobert-Laugier, C, Fortier, G, Ballet, J-J (2002) Detection of Sarcocystis neurona antibodies in French horses with neurological signs, Int J Parasitol, 32:481-485. 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.
  10. ↑ Goehring, L.S (2001) Sloet van Oldruitenborgh-Oosterbaan MM: Equine protozoal myeloencephalitis in the Netherlands? An overview, Tijdschr Diergeneeskd, 126:346-351. 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.
  11. ↑ Saville, W.J.A, Reed, S.M, Granstrom, D.E, Morley, P.S (1997) Some epidemiologic aspects of equine protozoal myeloencephalitis. Proceedings of the Annual Convention of the AAEP, 43:6-7.
  12. ↑ NAHMS (2000): Equine protozoal myeloencephalitis in the US, Ft Collins, CO, USDA:APHIS:VS, CEAH, National Animal Health Monitoring System. 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.
  13. ↑ MacKay, R.J, Davis, S.W, Dubey, J.P (1992) Equine protozoal myeloencephalitis, Compend Contin Educ Pract Vet, 14:1359-1367. 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.
  14. ↑ Fayer, R, Mayhew, I.G, Baird, J.D, Dill, S.G, Foreman, J.H, Fox, J.C, Higgins, R.J Higgins, Reed, S.M, Ruoff, W.W, Sweeney, R.W, Tuttle, P (1990) Epidemiology of equine protozoal myeloencephalitis in North America based on histologically confirmed cases, J Vet Intern Med, 4:54-57. 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.
  15. ↑ Boy, M.G, Galligan, D.T, Divers, T.J (1990) Protozoal encephalomyelitis in horses: 82 cases (1972-1986), J Am Vet Med Assoc, 196:632-634. 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.
  16. ↑ Saville, W.J, Reed, S.M, Morley, P.S, Granstrom, D.E, Kohn, C.W, Hinchcliff, K.W, Wittum, T.E (2000) Analysis of risk factors for the development of equine protozoal myeloencephalitis in horses. J Am Vet Med Assoc, 217:1174-1180. 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.
  17. ↑ Saville, W.J.A, Reed, S.M, Morley, P.S (1999) Examination of risk factors for equine protozoal myeloencephalitis. Proceedings of the Annual Convention of the AAEP, 45:48-49.
  18. ↑ Tillotson, K, McCue, P.M, Granstrom, D.E, Dargatz, D.A, Smith, M.O, Traub-Dargatz, J.L (1999) Seroprevalence of antibodies to Sarcocystis neurona in horses residing in northern Colorado, J Equine Vet Sci, 19:122-126. 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.
  19. ↑ Moore, L.A, Johnson, P.J, Messer, N.T, Kline, K.L, Crump, L.M, Knibb, J.R (1997) Management of headshaking in three horses by treatment for protozoal myeloencephalitis Vet Rec 141:264-267.
  20. ↑ Dunigan, C.E, Oglesbee, M.J, Podell, M 'et al.' (1995) Seizure activity associated with equine protozoal myeloencephalitis, Prog Vet Neurol, 6:50-54. 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.
  21. ↑ 21.0 21.1 21.2 21.3 21.4 Merck & Co (2008) The Merck Veterinary Manual (Eighth Edition), Merial
  22. ↑ Mayhew, I.G, deLahunta, A, Whitlock, R.H, Krook, L, Tasker, J.B (1978) Spinal cord disease in the horse, Cornell Vet, 68(Suppl 8):110-120. In: 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.
  23. ↑ 23.0 23.1 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.
  24. ↑ 24.0 24.1 24.2 24.3 24.4 24.5 24.6 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.
  25. ↑ 25.0 25.1 25.2 25.3 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.
  26. ↑ 26.0 26.1 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.
  27. ↑ 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.
  28. ↑ 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.
  29. ↑ 29.0 29.1 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.
  30. ↑ Scaratt, W.K, Jortner, B.S (1985) Neuritis of the cauda equina in a yearling filly. Compend Contin Educ Pract Vet, 7:S197-S202. In: Saville, W.J (2010) Polyneuritis equi in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) Equine Internal Medicine (Third Edition), Saunders, Chapter 12.
  31. ↑ Granstrom, D.E, Dubey, J.P, Giles, R.C (1994) Equine protozoal myeloencephalitis: biology and epidemiology. In Nakajima, H, Plowright, W, editors: Refereed Proceedings, Newmarket, England, R & W Publications. In: Saville, W.J (2010) Polyneuritis equi in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) Equine Internal Medicine (Third Edition), Saunders, Chapter 12.
  32. ↑ 32.0 32.1 Nout, Y.S (2010) Equine Degenerative Myeloencephalopathy in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) Equine Internal Medicine (Third Edition), Saunders, Chapter 12.
  33. ↑ Mayhew, I.G, deLahunta, A, Whitlock, R.H, Krook, L, Tasker, J.B (1978) Spinal cord disease in the horse, Cornell Vet, 68(Suppl 8):1-207. In: Nout, Y.S (2010) Equine Degenerative Myeloencephalopathy in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) Equine Internal Medicine (Third Edition), Saunders, Chapter 12.
  34. ↑ Jose-Cunilleras, E (2010) Verminous Encephalomyelitis in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) Equine Internal Medicine (Third Edition), Saunders, Chapter 12.
  35. ↑ 35.0 35.1 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.
  36. ↑ Smith, P.M, Jeffery, N.D (2005) Spinal shock - comparative aspects and clinical relevance. J Vet Intern Med, 19:788-793. In: Nout, Y.S (2010) Central Nervous System Trauma in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) Equine Internal Medicine (Third Edition), Saunders, Chapter 12.
  37. ↑ Nout, Y.S (2010) Central Nervous System Trauma in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) Equine Internal Medicine (Third Edition), Saunders, Chapter 12.
  38. ↑ Watson, A.G, Mayhew, I.G (1986) Familial congenital occipitoatlantoaxial malformation (OAAM) in the Arabian horse. Spine, 11:334-339. In: 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.
  39. ↑ Sellon, D.C (2010) Miscellaneous Neurologic Disorders in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) Equine Internal Medicine (Third Edition), Saunders, Chapter 12.
  40. ↑ Talcott, P (2010) Toxicoses causing signs relating to the urinary system in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) Equine Internal Medicine (Third Edition), Saunders, Chapter 22.
  41. ↑ Talcott, P (2010) Toxicoses causing signs relating to the urinary system in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) Equine Internal Medicine (Third Edition), Saunders, Chapter 22.
  42. ↑ 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.
  43. ↑ 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.
  44. ↑ 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.
Retrieved from "https://en.wikivet.net/index.php?title=Equine_Protozoal_Myeloencephalitis&oldid=73853"