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Basics ⬇

Outline

BASICS

Definition!!navigator!!

Multifocal neurologic disease of horses caused by Sarcocystis neuronaand Neospora hughesi.

Pathophysiology!!navigator!!

  • Infection results from ingestion of sporocysts of S. neurona in feed and water contaminated with feces of opossums, the definitive host
  • Sporocysts can be transmitted by vectors such as birds, rodents, and insects
  • Sporocysts excyst in the horse's small intestine, releasing sporozoites that penetrate the enterocytes and enter the bloodstream
  • 2 rounds of replication (i.e. merogony) occur, and S. neurona invade the entire organism before forming sarcocysts in the muscles of intermediate hosts, including horses
  • Parasites appear to gain access to the CNS either by direct penetration of the blood–brain barrier or through infected white blood cells. Merozoites multiply within neurons and leukocytes, resulting in cell death
  • Clinical signs are caused by neuronal loss and inflammation and swelling, which disrupt normal CNS architecture, compromise blood flow, and reduce oxygen delivery
  • Incubation time can be as short as 10 days but latent infections can persist for months
  • Life cycle of N. hughesi is not well understood but infection can occur transplacentally (or vertical infection was described)

Systems Affected!!navigator!!

  • Nervous—multifocal CNS infection results in variable sensory, motor, and cognitive dysfunction; cranial nerve deficits can occur
  • Neuromuscular—discrete, neurogenic muscle atrophy and weakness are common
  • Musculoskeletal—occasional secondary injuries and soreness from ataxia; asymmetric muscle weakness/atrophy
  • Gastrointestinal—cranial nerve signs associated with prehension, mastication, and swallowing; loss of anal tone
  • Skin—hyporeflexia, discrete areas of sensory loss and hyperhidrosis
  • Respiratory—laryngeal hemiplegia and pneumonia secondary to dysphagia
  • Ophthalmic—loss of ocular reflexes and blindness
  • Renal/urologic—urinary incontinence

Genetics!!navigator!!

No apparent genetic predisposition.

Incidence/Prevalence!!navigator!!

  • Seroprevalence of S. neurona reaches approximately 50% in many parts of the USA, 70% in Brazil, and 35% in Argentina
  • Incidence of the disease is low, with 0.014% of the population of horses affected in the USA
  • Seroprevalence of Neospora spp. in North and South America is very low—3.4% and 2.5%, respectively

Geographic Distribution!!navigator!!

  • The geographic range of EPM cases is defined by the distribution of the opossum
  • Native cases of EPM have only been reported in North and South America
  • Cases of neosporosis have been described in the USA and in France

Signalment!!navigator!!

Breed Predilections

Thoroughbreds, Standardbreds, and Quarter Horses are most frequently affected.

Mean Age and Range

Horses may be affected at any age (3 months to 30 years of age). The majority of the cases confirmed at postmortem were <4 years old.

Predominant Sex

Male Standardbreds might be at greater risks.

Signs!!navigator!!

General Comments

  • There is a great variation in clinical signs due to multifocal localization of the parasites in the CNS
  • The onset of the disease may be acute or insidious and can progress rapidly or remain stable for a long period of time

Historical Findings

  • Apparent lameness from asymmetrical ataxia and muscle weakness is the most common clinical complaint
  • Muscle atrophy, sore back, and cranial nerve deficits also may be reported

Physical Examination Findings

  • Affected horses are usually bright and alert
  • Clinical signs suggestive of spinal cord lesions, with variable degrees of ataxia and paresis in 1 or more limbs, are the most frequent finding (see Web Video 1)
  • Localized muscle atrophy, head tilt, facial paralysis, diminished ocular reflexes, poor prehension, mastication or dysphagia, laryngeal hemiplegia, urinary incontinence, localized sweating, seizure, and head shaking are also common

Causes!!navigator!!

  • S. neurona
  • N. hughesi

Risk Factors!!navigator!!

  • Opossums or previous diagnosis of EPM on the premises
  • Stress or adverse health event <90 days before presentation

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

  • Ataxia and paresis often confused with lameness
  • Cervical vertebral malformation—has similar breed predilection and usually produces symmetric ataxia
  • Trauma—history, external evidence of injury, and anatomic localization to a single area of the CNS are common
  • Equine degenerative myeloencephalopathy—progressive, symmetrical ataxia, and paresis in horses <2 years
  • Equine herpesvirus 1 myeloencephalopathy—typically affects more than 1 horse in a group and often follows respiratory disease. It is commonly associated with symmetric, posterior ataxia and paresis, bladder dysfunction, and loss of tail and anal tone
  • Equine viral encephalitis (West Nile virus, Eastern equine encephalitis, Western equine encephalitis, Venezuelan equine encephalitis)—depression and fever
  • Any conditions causing central and peripheral nervous system dysfunctions

CBC/Biochemistry/Urinalysis!!navigator!!

CBC and serum biochemistry are usually unremarkable.

Other Laboratory Tests!!navigator!!

  • Gold standard remains postmortem identification of characteristic lesions and parasites within the CNS. Immunohistology can help identify the parasites on fixed tissues
  • WB—positive serology is only indicative of exposure to the parasite. Negative tests indicate a high probability that the horse is not infected with S. neurona
  • In a study on 234 horses, sensitivity of WB on CSF was 87–88% regardless of whether the horses showed signs of neurologic diseases. Specificity reported on CSF varies from 44% to 60% depending on the presence or absence of neurologic signs, respectively
  • False-positive results on CSF samples may occur due to blood contamination of the CSF, subclinical infection with other concurrent neurologic disease, crossreactivity with other Sarcocystis or Neospora spp., or natural passage of antibody from the blood to the CSF after vaccination or colostrum ingestion
  • IFAT—sensitivity and specificity using serum samples of horses naturally infected with S. neurona are 83.3% and 96.9%, respectively. Using CSF, sensitivity is 100% and specificity is 99%
  • ELISA to detect S. neurona-specific immunoglobulin G has been described. Sensitivity and specificity are 95.5% and 92.9%, respectively
  • PCR detection of S. neurona DNA on the CSF has a high specificity but poor sensitivity
  • IFAT is more accurate to diagnose N. hughesi-infected horses than ELISA and direct agglutination test. Sensitivity is 100% and specificity varies from 71.5% to 100% depending on the cutoff value

Imaging!!navigator!!

Lesions localized in the brain, brainstem, and cervical spinal cord can be visualized using CT/MRI.

Other Diagnostic Procedures!!navigator!!

  • CSF is usually within normal limits, although its analysis may help rule out other diseases
  • Cytology on the CSF—more than 50 red blood cells per μL indicates blood contamination and prevents interpretation of a positive WB

Pathologic Findings!!navigator!!

  • Gross lesions not always visible at necropsy
  • CNS lesions due to S. neurona are commonly multifocal, characterized by hemorrhage and necrosis in the brain, brainstem, and spinal cord. Infective organisms are found primarily in neurons but also occasionally in leukocytes and vascular endothelium
  • N. hughesi causes multifocal granulomas in the CNS

Treatment ⬆ ⬇

Outline

TREATMENT

Aims!!navigator!!

  • Stopping progression of the disease
  • Improving the neurologic status of the horse
  • Preventing lesions from self-trauma
  • Preventing relapse when possible

Appropriate Health Care!!navigator!!

General supportive care in horses with severe neurologic dysfunction primarily aimed at avoiding self-traumatic injuries (deep bedding, sling support, and protective gear).

Nursing Care!!navigator!!

  • Severely ataxic horses should be confined in a heavily bedded box stall
  • Turning of the recumbent horse must be attempted every 2–6 h
  • Legs should be bandaged to avoid traumatic injuries
  • Adequate nutritional support must be provided. Diets and routes of administration must be adapted to each patient

Activity!!navigator!!

  • Prolonged inactivity does not enhance recovery
  • However, premature return to heavy work may prolong the time to recovery and promote relapse

Diet!!navigator!!

  • Use of folate inhibitors may result in bone marrow suppression and anemia. If life-threatening anemia develops, discontinue medication for 2–3 weeks to allow recovery or switch to an alternative medication. High-quality pasture and alfalfa hay are excellent sources of folinic acid and highly recommended during treatment. Folic acid is poorly absorbed by the horse and has been associated with toxicity
  • Supplementation with vitamin E 6000–10 000 IU PO daily has been recommended during therapy and rehabilitation

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

  • Ponazuril (Marquis, Bayer) is administered orally at 5 mg/kg daily for 28 days and is well tolerated in horses. Few adverse effects have been described at recommended dosages
  • Oral administration of nitazoxanide (Navigator, Idexx Pharmaceuticals) starts at 25 mg/kg daily for 5 days and then 50 mg/kg daily for a total of 28 days
  • Folate inhibitors are still widely used at 20 mg/kg sulfadiazine and 1.0 mg/kg pyrimethamine orally daily for 4–6 months or at least 1 month after the horse stops showing further improvement. Many veterinarians now recommend 1.5–2.0-fold the standard dose of pyrimethamine for the initial treatment or after 30 days without satisfactory progress. The combination should be given on an empty stomach to prevent interference with absorption from the gut
  • Administration of flunixin meglumine (1.1 mg/kg BID) or phenylbutazone (2.2 mg/kg BID) during the first 1–2 weeks of treatment and any time the condition appears to worsen may help minimize further damage due to parasite death and the host response
  • DMSO (1.0 g/kg in 10% saline IV daily for 3 days) may be beneficial
  • Use of dexamethasone (0.05 mg/kg IV daily or BID) in severely affected horses may help reduce CNS inflammation but remains controversial
  • Treatment of N. hughesi remains a challenge. In 1 report, the parasite was not affected by treatment with folate inhibitors and nitazoxanide, while in vitro studies indicate its susceptibility to those compounds

Contraindications!!navigator!!

Known sensitivity to 1 of the drugs.

Precautions!!navigator!!

  • Corticosteroids should be used with caution because they can suppress the immune response to the parasite. Their use should not exceed 1–3 days to avoid exacerbating the disease
  • Fatal enterocolitis, anorexia, weight loss, depression, colic, discoloration of the urine, fever, peripheral edema, and laminitis have been described in horses treated with nitazoxanide
  • Stallions may be at increased risks of developing laminitis while treated with nitazoxanide
  • Folic acid supplementation in horses treated with folate inhibitors may paradoxically exacerbate the deficiency
  • Abortion and decreased stallion fertility may occur using folate inhibitors

Possible Interactions!!navigator!!

Use of potentiated sulfas and pyrimethamine may increase the side effects of folic acid depletion.

Alternative Drugs!!navigator!!

  • Diclazuril and toltrazuril (5–10 mg/kg PO daily for 28 days) have been used in the treatment of EPM in the horse. Their efficacy appears to be comparable to folate inhibitors
  • Immunostimulants such as levamisole, killed Propionibacterium acnes, and mycobacterial cell wall extract have been recommended, but their efficacy has not been documented

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

  • Neurologic examination of affected horses is recommended at regular intervals during treatment
  • Relapse may occur in 10–25% of horses
  • To reduce the relapse rate, medication should not be discontinued until CSF becomes negative, but some horses remain CSF positive for an extended period after full recovery or stabilization
  • The relapse rate among horses with negative CSF at the time treatment is stopped has been extremely low
  • When using folate inhibitors, monthly CBCs are recommended to monitor anemia

Prevention/Avoidance!!navigator!!

  • Ataxic horses represent a risk for themselves and their handlers
  • Management should aim at preventing physical stress from injury and bacterial infection. Long trailer rides are stressful and commonly mentioned in clinical histories of affected horses
  • Prevention should aim at limiting the access of opossums and other wildlife to the horse's environment, feed, and water supply

Possible Complications!!navigator!!

Secondary injuries may occur from ataxia. Keep performance animals out of training during therapy.

Expected Course and Prognosis!!navigator!!

  • Regardless of treatment used, improvement usually varies between 60% and 75%
  • Full recovery rate are <25%. Mildly affected horses treated early in the course of infection have a better prognosis. Improvement often is observed during the first week of therapy and frequently progresses steadily for several weeks. The rate of improvement typically slows as the horse gradually improves over many weeks, until a plateau is reached. Chronic signs of CNS damage (e.g. muscle atrophy) rarely improve

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Associated Conditions!!navigator!!

Secondary injuries.

Zoonotic Potential!!navigator!!

N/A

Pregnancy/Fertility/Breeding!!navigator!!

Transplacental transmission of N. hughesi is documented but not of S. neurona. Abortion and death of foals born from mares treated with folate inhibitors and supplemented with folic acid and vitamin E are reported.

Abbreviations!!navigator!!

  • CNS = central nervous system
  • CSF = cerebrospinal fluid
  • CT = computed tomography
  • DMSO = dimethyl sulfoxide
  • ELISA = enzyme-linked immunosorbent assay
  • EPM = equine protozoal myeloencephalitis
  • IFAT = immunofluorescence antibody test
  • MRI = magnetic resonance imaging
  • PCR = polymerase chain reaction
  • WB = western blot test

Suggested Reading ⬆ ⬇

Furr M, MacKay R, Granstorm D. Clinical diagnosis of equine protozoal myeloencephalitis (EPM). J Vet Intern Med 2002;16:618–621.

Packham AE, Conrad PA, Wilson WD, et al. Qualitative evaluation of selective tests for detection of Neospora hughesi antibodies in serum and cerebrospinal fluid of experimentally infected horses. J Parasitol 2002;88:1239–1246.

Sellon DC, Dubey JP. Equine protozoal myeloencephalitis. In: Sellon DC, Long MT, eds. Equine Infectious Diseases. St. Louis, MO: Saunders, 2006:453–464.

Author(s) ⬆

Author: Laureline Lecoq

Consulting Editor: Caroline N. Hahn