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Differential diagnosis for horses suspected to have Sarcocystis neurona infection may be any disease affecting the central nervous system, although, depending upon the neuroanatomic localization certain problems may be more probable. That is to say, in a horse with weakness, ataxia and spasticity of all four limbs with no muscle atrophy or cranial nerve deficits, the horse may have cervical vertebral stenotic myelopathy or equine degenerative myeloencephalopathy. Both affect young horses (1-3 years of age), but CVM occurs more often in males. The clinical signs are often symmetric with the hindlimbs usually a grade worse than the forelimbs. The signs may be exaggerated by flexing or hyperextending the neck.
Equine herpesvirus myeloencephalitis (EHV1) often has an acute onset following an episode of fever, cough and nasal discharge or following one or more abortions on a farm. This condition often affects more than one horse on a farm. Herpesvirus has a rapid onset and often results in severe hindlimb weakness and ataxia along with bladder dysfunction. Urine dribbling may sometimes occur. The ataxia and weakness is usually symmetric and may result in recumbency. Occasionally the horses will dogsit. Cranial nerve involvement is not common.
Another disease which must be considered as a differential for EPM is Polyneuritis Equi. This disease can occur both acutely and insidiously. It is more common in mature horses and usually starts with hyperesthesia progressing to anesthesia. There is progressive paralysis of the tail, rectum, bladder and urethra leading to urine dribbling. Rear limb ataxia with gluteal atrophy may be present. Asymmetric cranial nerve deficits with involvement of cranial nerves five, seven and eight have been reported in 50% of the cases.
Verminous myeloencephalitis should also be considered as the signs are extremely variable depending on the parasite's migratory pathway. Diffuse or multifocal brain and spinal cord lesions have been reported. The onset is usually sudden with rapid deterioration and death. The incidence of this disease is very low, perhaps due to more intense parasite control.