Equine Protozoal Myeloencephalitis

Also known as:

EPM Equine protozoal myelitis Equine protozoal encephalomyelitis

Description

A progressive, infectious,neurological disease of horses, endemic in the USA and only encountered elsewhere in imported equids. EPM is one of the most frequently diagnosed neurological conditions of the Western Hemisphere and the principal differential for multifocal, asymmetric progressive central nervous system (CNS) disease. 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 The disease is not contagious.

Aetiology

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

Epidemiology

In endemic areas of the United States, around a quarter of referrals for equine neurological disease are attributed to EPM. 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. The disease has been identified in parts of Central and South America, southern Canada and across most of the USA.. EPM is noted occasionally in other countries, in horses that have been imported from the Americas. 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, although cross-reacting antigens on the immunoblot test may explain this discrepancy.

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

Increasing age and environmental temperature have been associated with an increased seroprevalence of S. neurona. Seroprevalence for this species is typically higher than for N. hughesi.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.Case clustering may operate where all the risk factors occur, but the majority of cases appear in isolation.

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.

The causative pathogen(s) have been isolated form 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. Foal infection may be possible.

History

Typically an insidious onset ataxia, but the presentation may be acute and severe.

Clinical Signs

The disease onset may be acute, peracute of chronic. The insidious onset is most typical and with such cases, the clinical examination may reveal a bright, alert horse bright perhaps with some focal muscle atrophy.(Furr)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 (EPM3)

Spinal cord:

• Ataxia and paresis

Ataxia or paresis of one or more limbs: stumbling, falling, knuckling and toe dragging. Sacrococcygeal involvement: mimics polyneuritis equi. Cranial nerve signs: loss of tongue tone, loss of sensation to the face and unilateral facial paralysis. Brain involvement: dysphagia, circling, head tilt or recumbency(EPM3)

Signs: asymmetrical weakness, ataxia, vestibular disease (peripheral or central) peripheral neuropathy, ill-defined hindlimb lameness, asymmetric muscle atrophy. (Vetstream)

Spinal cord infection :

• Ataxia and weakness (hindlimbs > forelimbs) - often asymmetrical.
• Apparent lameness, particularly atypical or slight gait asymmetry of hindlimbs (not alleviated by local anesthesia).
• Abnormal placing reactions.
• Focal muscle atrophy (individual muscle grps (Pasq)- evident anywhere especially gluteal muscles - often asymmetrical.
• Generalized muscle atrophy/loss of condition

Lesions of the brainstem, cerebrum or cerebellum are less frequently recognized: Cranial nerve dysfunction (<5% of cases) - any can be affected:

• Atrophy of temporalis/masseter muscles (V)
• Dysphagia (V, VII, IX, X, XII)
• Abnormalities of facial (VII) and vestibulocochlear (VIII) nerves often observed together:
• VIII - vestibular signs of nystagmus, head tilt, base-wide stance
• VII - muzzle deviation, ptosis, ear droop
• Dorsal displacement of soft palate (IX, X)
• Laryngeal hemiplegia (X)

Severe cases may:

• Inability to stand.
• Inability to swallow.

Infection of cerebrum, basal nuclei, cerebellum: Focal cerebral problems:

• Seizures (may be the only clinical sign)(82 in Furr)
• Abnormal EEG.
• Asymmetrical central blindness
• Facial hypalgesia
• Cerebellar ataxia
• Altered behavior
• Depression
• Narcolepsy-like syndrome

Nerve damage/ataxia injuries to muscle tendons or ligaments:

• Upward fixation of the patella
• Exertional rhabdomyolysis .
• Back pain.
• Gait abnormality.

Any gait abnormality in galloping/trotting race/dressage horses while in training which cannot be attributed to musculoskeletal abnormality may result from EPM and requires careful neurologic evaluation.(Vetstream)

Headshaking(EPM 7)

Gait abnormality (peracute or acute) - 1 or all 4 limbs depending on where migrates, asymmetrical (because multifocal), ataxia, paresis & spasticity - knuckling, circumduction, crossing over, tetraparesis - areflexia, hyporeflexia (LMN) or hyperreflexia (UMN) depending on site of lesion, localized areas of sensory deficits, 'strip sweating' localized areas (dermatomes, sympathetic white matter tracts), cerebellar, brain stem (less common) or cerebral signs, cranial nn - head tilt, facial paralysis, circling, nystagmus, dysphagia, blindness with or without abnormal pupillary reflexes, untreated progressive to recumbency in 14days to 6mths (Pasq)

The three characteristic 'As' of EPM (ataxia, asymmetry, atrophy) suggest multifocal or diffuse disease, but are not pathognomonic. It has been suggested that rapidly progressive presentations reflect brainstem lesions. Spinal cord signs are most commonly seen and may include:

• asymmetric or symmetric paresis, spasticity and ataxia of one to four limbs
• focal or general muscle atrophy
• apparent lameness
• back pain
• loss of reflexes or cutaneous anaesthesia
• abnormal menace response

Without treatment, progression to recumbency and death is likely. This deterioration may occur smoothly or spasmodically over hours to years. (Merck)

Differential Diagnoses

The protozoan can migrate to any region of the CNS, 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 with spasticity and dysmetria, good retention of strength, no muscle wasting. NB:can be concurrent with EPM.	Plain lateral radiography of C1 to T1, myelography.
West Nile encephalitis	Systemically ill, pyrexia. Difficult to differentiate if horse is afebrile and has no excessive muscle fasciculations.	Leukogram, CSF analysis, IgM capture ELISA, plaque reduction neutralization test (PRNT).
WEE	Systemically ill, pyrexia, abnormal motor function.	Leukogram, ELISA, titres, virus isolation.
EEE	Systemically ill, pyrexia, abnormal motor function, rapidly progressive.	Leukogram, CSF analysis, ELISA, titres, virus isolation.
VEE	Systemically ill, pyrexia.	Leukogram, IgM ELISA
Equine herpesvirus-1 myeloencephalopathy	Sudden onset and early stabilization of neurological signs, multiple horses affected, recent fever, abortion. Dysuria not often seen in EPM.	CSF analysis, PCR, titres, virus isolation.
Rabies	Rapid progression, behavioural alterations, depression, seizure, coma.	Post-mortem fluorescent antibody testing of brain required for definitive diagnosis.
Polyneuritis equi (previously cauda equina neuritis)	Cranial nerve deficits are peripheral with no change in attitude.	Western blot analysis of CSF.
Equine degenerative myeloencephalopathy	Symmetrical signs.	May get increased CSF creatinine kinase (CK) and reduced serum Vitamin E concentrations but these are unreliable for ante mortem diagnosis.
Verminous encephalomyelitis	Acute onset.	CSF analysis.
Bacterial meningoencephalitis	Stiff neck.
CNS abscessation due to 'bastard strangles'	History of Streptococcus equi subsp. equi infection.	CSF analysis (severe, suppurative inflammation), culture of CSF.
Spinal trauma	History (usually acute onset neurological signs), usually solitary lesion localised by neurological exam.	Radiography, myelography, CT, MRI, nuclear scintigraphy, ultrasound, CSF analysis, nerve conduction velocities, EMG, transcranial magnetic stimulation.
Occipito-atlanto-axial malformation (OAAM)	Deficits develop before 6mths in Arabian horse.	Radiography.
Spinal tumor	Signs can usually be localized to one region of the CNS.	CT, MRI. Definitive diagnosis requires cytology, biopsy, histopathology or CSF analysis.
Sorghum cystitis/ataxia	Posterior ataxia or paresis, cystitis, history of grazing Sorghum species	Demonstration of cystitis or pyelonephritis by laboratory methods, but not specific.

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.

Gross exam

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

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. In around 25% of cases, schizonts or merozoites may be found in the neuronal cytoplasm. Less frequently, protozoa parasitize intravascular and tissue neutrophils and eosinophils, capillary endothelial cells and myelinated axons. Free merozoites may be seen in necrotic regions. If organisms are absent, the diagnosis relies on recognition of the inflammatory changes described above.

Prognosis

Depends on duration and severity of neurological signs but clinical resolution is more likely if the condition is diagnosed and treated early. 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. 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 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. The vaccine proved to be ineffective in the prevention of EPM and has since been removed from the market. There is evidence to suggest that the antiprotozoal, ponazuril, may be useful prophylactically to reduce the incidence and severity of clinical signs. Implementing such a regime prior to and during stressful events may be beneficial, although the cost is likely to be prohibitive.