FINAL DIAGNOSIS:
Ataxia with Equine Herpes Virus Type 1 Infection in
a Horse
History: A Thorough-bred mare, reportedly 17.5
years old, was submitted dead for necropsy to the Purdue
Animal Disease Diagnostic Laboratory. The history included
marked asymmetric ataxia for approximately four months.
The animal did not respond to treatment for equine protozoal
myeloencephalitis (EPM) and was euthanized. The owner reported
herpes virus infection earlier in the year.
Gross Findings: Scattered petechial hemorrhages
were seen in sections of spinal cord at the level of T17-L3,
predominantly in the ventral and ventrolateral funiculi.
The surrounding parenchyma was occasionally soft, with gray
discoloration. The brain was grossly normal.
Histopathologic Findings: The main lesions in the
spinal cord consisted of wallerian-like degeneration accompanied
by non-suppurative myelitis with vasculitis. The degenerative
lesions were present in all the sections examined, accompanied
by minimal inflammatory lesions, with the caudal thoracic
and cranial lumbar segments being the most severely affected,
accompanied by multifocal hemorrhage. Multifocal non-suppurative
encephalitis was observed in all sections of brain examined
except the frontal cerebral cortex.
Discussion: The inflammatory reaction in sections
of spinal cord from this animal was centered on blood vessels,
occasionally accompanied by hemorrhage. These lesions are
highly suggestive of a primary vasculitis with secondary
ischemic injury to the neuroparenchyma. Immunohistochemistry
revealed a positive staining for equine herpes virus-1 (EHV-1)
antigen in smooth muscle cells of spinal arterioles, arteries,
and veins. PCR for West Nile virus on a sample of spinal
cord was negative. These results, as well as the reported
previous infection by this virus, are highly suggestive
of EHV-1 infection.
Herpes virus infection is ubiquitous in horses, and most
animals are infected by the first year of life. Neurologic
disease is an uncommon sequela to EHV-1 infection in horses
and is usually, but not invariably, associated with a recent
history of fever, abortion, or respiratory disease in the
affected animal or herdmates. Myeloencephalopathy due to
EHV-1 is commonly an epizootic disease, but may affect single
animals in a herd. Pregnant or lactating mares may be more
susceptible, although stallions, geldings, and foals have
also been affected with this disease.
Natural EHV-1 infection is acquired via inhalation or
ingestion of virus that is shed primarily from the nasopharynx.
The incubation period for signs of neurologic disease after
experimental and natural infection with EHV-1 is 6-10 days.
This form of EHV-1 infection can occur at any time of the
year, but the highest incidence is in the late winter, spring,
and early summer, perhaps reflecting the seasonal occurrence
of abortigenic EHV-1 infections during the same months.
Neurologic signs are of abrupt onset, and horses may be
found recumbent as the first evidence of the disease. Clinical
signs most often reflect spinal cord lesions; ataxia and
paresis of the pelvic limbs are common, and passive dribbling
of urine is a characteristic feature. Signs may be mild
and transient as recovery or compensation occurs with minimal
lesions. With severe lesions, recumbency occurs in 12-24
hours from the onset of neurological signs. Sometimes ascending
paralysis is observed and animals may die in coma or convulsion
or be euthanized because of secondary complications. Morbidity
rates ranging from less than 1% to almost 90% of exposed
individuals and mortality rates ranging from 0.5-43% of
in-contact horses have been reported.
The pathogenesis involves viral endotheliotropism and
associated vasculitis and thrombosis in the central nervous
system with resultant ischemia and myelomalacia. Immune
mechanisms have been implicated, but immunohistochemical
demonstration of EHV-1 antigen in neurons of affected horses
and association of myeloencephalopathy with certain EHV-1
strains indicate that primary viral neurotropism might also
occur. EHV-1 has been reported to maintain a latent state
in lymphoid tissues, leukocytes, and trigeminal ganglia. Reactivation of latent EHV-1 infection after stress situations
has been reported as a possible source of infection.
The cerebrospinal fluid from affected animals is often
xanthochromic with elevated protein but normal numbers of
cells (i.e., virtually none). During the early stage of
the infection, there is a cell-associated viremia, and virus
may be isolated from the buffy coat in affected horses;
however, failure to isolate EHV-1 does not rule out the
diagnosis. A 4-fold increase in serum neutralizing antibody
titer is considered diagnostic for EHV-1 infection, and
a single high titer (greater than 1:256) also suggests recent
natural infection. PCR in whole blood, nasopharyngeal swabs,
lymphoid tissues, and trigeminal ganglia is another valuable
technique in supporting a diagnosis of EHV-1 myeloencephalopathy,
but decreased or absent viral shedding due to stage of infection,
previous vaccination, or viral latency might affect the
viral DNA detection. Postmortem examination, including
spinal cord histopathology and immunohistochemistry, are
recommended to confirm the diagnosis of EHV-1 myelo-encephalopathy.
No specific treatment of equine herpes myeloencephalopathy
is currently available; thus, management of horses with
this condition is directed toward supportive nursing, nutritional
care, and reduction of central nervous system inflammation.
Treatment with the antiviral agent acyclovir has been recommended. Further studies are required, however, to evaluate the thera-peutic
efficacy of antiviral agents in the treatment of neurologic
disease associated with EHV-1.
There is currently no known method to reliably prevent
the neurologic form of EHV-1 infection. None of the EHV-1
or EHV-4 vaccines currently available carry a claim that
they prevent EHV-1 myelo-encephalopathy, and the disease
has been observed in horses vaccinated regularly at 3-4
month intervals with inactivated and modified live vaccines.
Nevertheless, it is recommended to maintain appropriate
vaccination procedures in an attempt to reduce the incidence
of the other manifestations of EHV-1 infection and reduce
the magnitude of challenge experienced by in-contact horses. This may indirectly help prevent EHV-1 myeloencephalopathy.
This case emphasizes that EHV-1 infection, although of
rare occurrence, has to be considered as a possible cause
for gait abnormalities affecting single or multiple horses
on the premises, in addition to other viral myeloencephalitides,
including West Nile virus, rabies virus, and togaviral encephalomyelitis,
as well as equine protozoal myeloencephalitis, wobbler syndrome,
cervical vertebral fracture, degenerative myelopathy, and
a variety of plant and chemical intoxications.
-by Dr. Ingeborg Langohr, ADDL Graduate Student
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