Neurological diseases in horses encompass a range of disorders affecting the central and peripheral nervous systems. These conditions can arise from various etiologies, including infectious agents, genetic predispositions, trauma, or metabolic imbalances. Common neurological diseases in horses include equine protozoal myeloencephalitis (EPM), equine herpesvirus myeloencephalopathy (EHM), and cervical vertebral stenotic myelopathy (CVSM), also known as wobbler syndrome. Clinical signs associated with these diseases may include ataxia, weakness, altered gait, and changes in behavior or mental status. Diagnosis typically involves a combination of clinical evaluation, imaging techniques, and laboratory testing. This page compiles peer-reviewed research studies and scholarly articles that investigate the pathophysiology, diagnostic approaches, and treatment options for neurological diseases in equine populations.
Boukabache H, Gonzalez G, Helle T, Boudjadi Y, Migné C, Zientara S, Azizi A, Durand B, Laabassi F.Orthoflaviviruses are etiological agents of neurological diseases in equines. Horses are susceptible to equine Tick-borne encephalitis virus (TBEV), Usutu virus (USUV), and West Nile virus (WNV), although mostly WNV has been associated with clinical disease. The aim of the present study was to estimate the prevalence of TBEV, USUV and WNV in 289 healthy horses from nine provinces of Algeria. This study was conducted between March 2021 and December 2023. Sera that tested positive, doubtful, or negative close to the doubtful threshold in the Orthoflavivirus-ELISA were further tested by the virus...
Brown BN, Dahlgren AR, Ghosh S, Durbin-Johnson B, Willis A, Olivas C, York D, Grahn R, Bellone RR, Cortopassi GA, Miller AD, Brown CT, Woolard K....Equine Juvenile Spinocerebellar Ataxia (EJSCA) is a novel autosomal recessive neurologic disease in Quarter Horses. Affected foals display a progressive proprioceptive ataxia by 1-5 weeks of age, leading to recumbency and necessitating euthanasia. Whole genome sequencing was performed on 7 EJSCA cases and unaffected horses that included 4 obligate carriers, 4 unaffected half or full-siblings, and 28 unrelated, unaffected control Quarter Horses. An 82 kb region of association was identified (EquCab3.0, chr11: 6963986-7045999), containing 9 candidate SNPs across four genes (FADS6, FDXR, GRIN2C a...
Gomez DE, Suarez G, de Tonnerre DJ, Mallicote MF, Hernadez JA, Sanchez LC, Mackay RJ.Eastern equine encephalitis (EEE) is a highly fatal neurologic disease of horses, but data describing clinical presentation, epidemiology, and prognostic factors are limited. Objective: Describe the clinicopathologic and epidemiologic features of horses with EEE and identify factors associated with survival. Methods: One hundred four horses diagnosed with EEE presented with signs of diffuse brain disease. Methods: Retrospective case series of horses evaluated at a Veterinary Teaching Hospital (1979-2017). Medical records were reviewed for clinical findings, diagnostic results, and outcomes. Lo...
Espinosa MA, Lack A, Kenney D, Arroyo LG.Equine herpesvirus type 1 (EHV-1) is an important viral pathogen in horses, associated with diverse clinical manifestations including fever, upper and lower respiratory disease, neurological signs, ocular disease, and abortion. Currently, EHV-1 variants (genotypes) are classified based on a single nucleotide polymorphism mutation of the open reading frame 30 (ORF30). Unassigned: The aim of this retrospective study was to evaluate the EHV-1 genotypes present in horses with various clinical presentations, including respiratory disease, abortion, and neurological disease, at a referral center in ...
Helber L, Wagner B, Leeth CM, LeRoith T, Cecere TE, Lahmers KK, Andrews FM, Hay AN, Werre SR, Johnson AL, Clark CK, Pusterla N, Reed SM, Lindsay DS....Currently, little is known about the exact role of immunopathology in equine protozoal myeloencephalitis (EPM), including the ability to persist after anti-protozoal treatment. The main objectives of this study were to determine whether is present in the CNS in horses with EPM, including previously treated cases, and to evaluate the associated histopathology and immune response. For this study, control ( = 10) and horses with EPM ( = 9) were confirmed based on our inclusion criteria. Based on our preliminary data, we classified horses with EPM and clinical signs for >6 months as...
Federico F, Amie W, Alzbeta C, Anders J, David LP, Mandy PJ.Cerebrospinal fluid (CSF) is a valuable source of biomarkers for neurological diseases, but detection of low-abundance proteins is often masked by highly abundant proteins. Enrichment strategies can enhance proteomic coverage and improve biomarker discovery, yet comparative evaluations of such methods in equine CSF are limited. Objective: This study compared the ProteoMiner Small-Capacity Enrichment Kit and the PreOmics Enrich-iST Kit for their ability to deplete high-abundance proteins and enhance detection of low-abundance proteins relevant to neuropathology. Methods: Equine CSF samples were...
Weintraub L, Fielding CL, Bouton J, Rhodes D.Rattlesnake envenomation is a common emergency in horses in California. Rattlesnakes belong to a group of venomous snakes: pit vipers. The Northern Pacific Rattlesnake (), a subspecies of the Western Rattlesnake, is the most widespread rattlesnake in California (1). A 5-year-old miniature horse mare presented for a presumed Western Rattlesnake bite. The owners found the horse the morning of presentation with severe facial swelling and the horse was housed in an area where rattlesnakes are commonly observed. The horse was reported to be normal the day prior to presentation. On blood examination...
Manso-Díaz G.Diagnostic imaging is essential for evaluating and managing neurologic disease in horses. Following clinical lesion, neurolocalization imaging modalities are often necessary to further characterize the disease process. However, which technology to use depends on various factors, including the patient's size, clinical signs, and the anatomic region. Current advances in imaging technology, in general, and the adaptation of different modalities for equine patients, in particular, have substantially improved our ability to evaluate the equine central nervous system. This article will summarize the...
West Nile virus (WNV) is a mosquito-borne flavivirus of growing importance for both human and equine health in Europe. Horses are highly susceptible to neurological disease and, because they share ecological exposure with humans, they represent valuable sentinels for detecting local viral circulation within a One Health framework. However, diagnosis of WNV infection in equines is complicated by the short and low-level viraemia, which limits the sensitivity of molecular assays, and by serological cross-reactivity with related flaviviruses and the confounding effects of vaccination. In this narr...
Palunas V, Fussell D, Helgert N, Long AE, Aitken MR, Abraham M.A 2-year-old Irish Sport Horse colt presented with acute, severe and rapidly progressive neurological signs, arriving recumbent to the hospital. Ante-mortem diagnostics did not reveal the cause of the recumbency, and the colt was euthanized after treatment and supportive care did not result in clinical improvement. A cranial cervical extradural mast cell tumour with eosinophilic granulomas and secondary compressive myelopathy with axonal degeneration was diagnosed on post-mortem evaluation. No other masses or clinically relevant findings were present, suggesting a primary neoplasm. Neoplasia a...
Sunderland KA, Affolter VK, Cassano JM, Berryhill EH, Morgan JM.To determine the main causes of death in aged horses residing at a retirement facility in California. Unassigned: A retrospective cross-sectional study design was utilized to evaluate signalment, medical history, and necropsy reports of horses aged 20 years or older at death and housed at a single retirement facility. All cases underwent a standard post mortem evaluation from 2010 through 2020 by the University of California-Davis William R. Pritchard Veterinary Medical Teaching Hospital. Euthanasia decisions were made by the retirement facility staff in consultation with a veterinarian. The m...
Cornelisse K, Ionescu AM.Keesjan Cornelisse and Andra-Maria Ionescu discuss the clinical presentation, investigation and diagnostic approach to a case of orthoflavivirus infection in a horse in south-west England.
Gräf T, Rodriguez MC, de Oliveira Brandão Y, Royer CA, do Nascimento Ferreira C, Confortin C, Zanluca C, Strottmann DM, Duarte Dos Santos CN....Rocio virus (ROCV), a neurotropic arbovirus of the genus, caused Brazil’s largest encephalitis outbreak in the 1970s but has since been rarely detected. We report the first ROCV encephalitis clinical case after nearly 40 years and isolated and sequenced the virus from CNS tissue of a horse. Metatranscriptomics enabled full-genome sequencing, revealing divergence from the reference sequence at an evolutionary rate of 5.8–7.0 × 10⁻⁴, consistent with . Thirty-one non-synonymous substitutions were identified, with the envelope protein most affected. Findings indicate ROCV cryptic circula...
Migliorisi A.The goal of this article is to provide the equine practitioners with a framework for a diagnostic algorithm for the patient presented with possible seizures/epilepsy. Using a comparative approach, a review of companion animal and human research is provided with the intention of expanding our current knowledge on seizure/epilepsy, as well as diagnostic and treatment strategies for equine patients.
Aleman M, Morales CJ.Idiopathic trigeminal-mediated headshaking is a painful neuropathic disorder characterized by sudden, violent, predominantly vertical head movements of unknown etiology. Clinical signs may be seasonal or persistent and triggered by light, sound, exercise, or tactile nasal stimulation. The pathophysiology is multifactorial, involving abnormal trigeminal nerve excitability influenced by hormonal, environmental, and dietary factors. Treatment is challenging and typically multimodal, aiming to reduce trigeminal hypersensitivity and improve quality of life.
Campos Schweitzer A, Mespoulhes-Rivière C, Perkins JD, Ducharme NG, Piercy RJ, Lynch N, Rossignol F.To evaluate functional and histopathologic outcomes of standing selective laryngeal reinnervation using the spinal accessory nerve (SAN) in horses with experimentally induced recurrent laryngeal neuropathy (RLN). Methods: Five Thoroughbred mares. Methods: Prospective cohort study. Methods: The horses underwent left recurrent laryngeal neurectomy followed 8 weeks later by selective laryngeal reinnervation using the SAN. Follow-up evaluations at 4.5, 6, 8, and 12 months included treadmill exercising endoscopy, ultrasonography of intrinsic laryngeal muscles, and percutaneous electrical stimul...
Schmidt S, Swagemakers JH, le Jeune SS.The cervical vertebral column in horses plays a crucial role in movement, posture, and performance and disorders affecting it can cause pain, ataxia, or lameness. This review discusses major acquired (traumatic, infectious, neoplastic) and degenerative (osteoarthritis, foraminal stenosis, intervertebral disc disease) conditions. Acquired lesions often arise from trauma, bacterial infection, or neoplasia, with clinical signs ranging from neck pain to neurologic deficits. Degenerative disorders, particularly osteoarthritis of articular process joints, are common in the caudal cervical spine and ...
Haussler KK.Congenital cervical vertebral anomalies in horses are structural changes in the neck vertebrae that develop during the fetal stage. These anomalies can vary in their severity and effects. Some horses may not show any clinical signs and can live normally, while others may develop serious problems such as spinal cord compression. This compression can lead to issues like ataxia or even paralysis, affecting the horse's mobility and quality of life. Recognizing and diagnosing these anomalies early are very important, as it helps guide decisions about the best treatment options and overall managemen...
Valberg SJ, Williams ZJ, Ames EG, Mickelson JR, Nout-Lomas YS, Landolt G, Sanz M, Gardner K.Equine myotonic dystrophy (eMD) is a rare neuromuscular disorder of undetermined origin marked by muscle hypertrophy and stiffness, dystrophic muscle histopathology, and myotonic discharges. In humans, myotonic dystrophy (DM) arises from trinucleotide repeat expansions in dystrophia myotonica protein kinase (DMPK) (DM1) or tetranucleotide expansions in cellular nucleic acid-binding protein (CNBP) (DM2), which disrupt mRNA processing and induce embryonic splicing patterns across multiple genes. In 6 eMD Quarter Horse types, (2-36 months-of-age) and 8 control Quarter Horses we determined: (1) fi...
Gordon S, Pusterla N, Finno CJ, Young A, Martínez-López B.Equine alphaherpesvirus-1 (EHV-1) is a highly contagious virus that can cause the neurological form, equine herpesvirus myeloencephalopathy (EHM). Understanding transmission-related risk factors is crucial for improving prevention strategies and guiding effective control measures. In this study, we collected data from 63 horses that had previously participated in the February 2022 winter horse show season at the Desert International Horse Park (DIHP) (26 cases and 37 controls) to identify host and management factors associated with EHV-1 infection and/or EHM development during the February 202...
de Chaisemartin C, Belluco S, Nottrott K.Dental masses such as odontogenic masses, heterotopic polydontia, or ectopic supernumerary teeth have been documented in the equine head. This is the first case report of a large maxillary sinus mass with 3 ectopic teeth in an adult horse. A 14-year-old warmblood gelding was presented for evaluation of chronic right-sided nasal discharge. After imaging exploration, surgery was performed on the standing horse with a conchofrontal sinus trephination and a large maxillary bone (MB) sinusotomy. The examinations revealed a sinusal mass in the right maxillary sinus covered by sinusal mucosa and surr...
Sjolin E, Espinosa D, Arroyo L, Kenney D, Lack A, Baird J.Listeriosis is caused by , a Gram-positive, facultative anaerobic, intracellular rod bacterium that can infect a wide variety of species. Listeriosis occurs in a diverse range of domestic and wild animals but is most commonly a disease of ruminants. Clinical signs include meningoencephalitis, typhlocolitis, septic arthritis, and abortions. Listeriosis in horses has been reported in several countries but is an uncommon diagnosis. This report describes clinical, bacteriological, histopathological, and immunohistochemical findings in 6 foals with neonatal septicemia from which was isolated. Key ...
Puccetti M, Beccati F, Pilati N.Femoral nerve neuropathy causes lameness, a condition clinically characterized by stifle's lack of extension with subsequent diminished lower limb function. This case report describes the ultrasonographic diagnosis of femoral neuropathy secondary to compression caused by myopathy of the iliopsoas muscle of an endurance horse during a competition. Transrectal ultrasonography played a pivotal role in diagnosis of the injury by assessment of the involved structures and monitoring of the healing process throughout the recovery period. The horse achieved complete recovery and successfully returned ...
Raftery AG, Gummery L, Garcia K, Mohite D, Capewell P, Sutton D.Equine trypanosomiasis is a neglected protozoal disease. Objective: To answer the study question: In equines what are the effects of disease management of trypanosomiasis on disease severity (individual level) and disease prevalence (population level) compared to no intervention? Methods: Systematic review. Methods: Studies were identified that described management of naturally occurring equine trypanosomiasis in any country following 'Preferred Reporting Items for Systematic Reviews and Meta-analyses' using eight international databases (1980-2022). Risk of bias was assessed using ROBINS-I. D...
Weber LA, Oltmanns H, Chiavaccini L, Pickles KJ, Roberts V, Kloock T, Niebuhr T, Feige K.Trigeminal-mediated headshaking (TMHS) in horses shares clinical features with human trigeminal neuralgia (HTN). Increased levels of the neuropeptide calcitonin gene-related peptide (CGRP) have been found in the blood and cerebrospinal fluid (CSF) of HTN patients. Inhibition of CGRP in humans has shown promise for pain relief. Data on CGRP in horses affected by TMHS are currently lacking but if quantifiable and validated, could assist in developing new diagnostic and more rational therapeutic approaches. Objective: This study aimed to quantify and correlate CGRP concentrations in the serum and...
Björnsdóttir S, Sigurðardóttir ÓG, Oddsdóttir C, Reynisdóttir I, Hanche-Olsen S, Gröndahl G.Acquired equine polyneuropathy is a neuromuscular syndrome characterized by digital extensor dysfunction, primarily affecting the pelvic limbs, with consistent, repeated knuckling. Despite being recognized as an emerging disease in Scandinavia since 1995, the aetiology remains unknown, and cases have been limited to Norway, Sweden, and Finland. Methods: On a combined breeding and training farm in Iceland, 30 out of 145 horses (21%) presented with acute pelvic weakness, pelvic limb digital extensor dysfunction, knuckling and/or recumbency, from May to August 2019. The affected horses, aged 2-9...
Kyle-LaBell E, Andersson A, Baughman B.Fibrocartilaginous embolic myelopathy (FCE) was diagnosed in a 15-year-old pony mare by histopathologic examination of the spinal cord. The horse was euthanized and submitted for necropsy following focal seizures and lateral recumbency for approximately 12 h. Histopathology of spinal cord segments C5-C7 revealed severe ischemic myelomalacia with intravascular amorphous material that stained positive with Alcian Blue, consistent with cartilaginous matrix. These features in addition to the acute onset of clinical signs are characteristic for FCE. This case report describes the clinical and histo...
Khan MZ, Ji Y, Fan X, Liu Y, Liu W, Wang C.Equine herpesvirus (EHV) infections represent a significant global veterinary and economic challenge affecting both horses and donkeys across all inhabited continents. This narrative review comprehensively examines the nine distinct EHV species (EHV-1 through EHV-9), their taxonomic classification within Alphaherpesvirinae and Gammaherpesvirinae subfamilies, and their diverse host tropism patterns. The complex molecular pathogenesis involves sophisticated viral glycoproteins (gK, gB, gC, gH, gM, gL, gG, gD, gI, gE) that orchestrate cellular invasion, immune evasion, and intercellular transmiss...
Wang L, Zheng R, Li Z, Zhang L.Recent increases in cases of western equine encephalitis (WEE) in South America have raised significant concerns about the virus's potential to cause an endemic disease due to its adaptation to mosquito vectors. Currently, there are no effective vaccines or treatments for WEEV, despite ongoing research into various biochemical products in animal models. The virus presents different pathological effects depending on the host. In humans, WEEV infection leads to central nervous system damage, resulting in encephalitis and severe neurological sequelae, which underscores the need for further resear...
Tallmadge RL, Laverack M, Lejeune M, Crossley B, Diel DG.Equid herpesvirus (EHV) 1 and -4 are common viral pathogens of horses that can cause upper respiratory disease, neurological disease, abortion, and death. As characteristic alphaherpesviruses, both EHV-1 and EHV-4 can establish latency, resulting in a lifelong carrier state in infected animals. Here we describe the development and validation of a rapid and sensitive multiplex real-time PCR assay (EHV1-4MP) that simultaneously detects EHV-1 and EHV-4 and includes an endogenous internal control - melanocortin 1 receptor (MC1R) - targeting the equid genome. The EHV1-4MP assay analytical sensitiv...
Band GP, van der Molen MW, Logan GD.In the stop-signal paradigm, subjects perform a standard two-choice reaction task in which, occasionally and unpredictably, a stop-signal is presented requiring the inhibition of the response to the choice signal. The stop-signal paradigm has been successfully applied to assess the ability to inhibit under a wide range of experimental conditions and in various populations. The current study presents a set of evidence-based guidelines for using the stop-signal paradigm. The evidence was derived from a series of simulations aimed at (a) examining the effects of experimental design features on in...
Andersson LS, Larhammar M, Memic F, Wootz H, Schwochow D, Rubin CJ, Patra K, Arnason T, Wellbring L, Hjälm G, Imsland F, Petersen JL, McCue ME....Locomotion in mammals relies on a central pattern-generating circuitry of spinal interneurons established during development that coordinates limb movement. These networks produce left-right alternation of limbs as well as coordinated activation of flexor and extensor muscles. Here we show that a premature stop codon in the DMRT3 gene has a major effect on the pattern of locomotion in horses. The mutation is permissive for the ability to perform alternate gaits and has a favourable effect on harness racing performance. Examination of wild-type and Dmrt3-null mice demonstrates that Dmrt3 is exp...
Marasas WF, Kellerman TS, Gelderblom WC, Coetzer JA, Thiel PG, van der Lugt JJ.Each of two horses was dosed by stomach tube with culture material on maize of Fusarium moniliforme MRC 826. One horse developed severe hepatosis and mild oedema of the brain after 6 doses of 2.5 g of culture material/kg body mass/day in 7 days. The second horse, in a similar experiment but at a dosage rate of 1.25 g/kg/day, developed mild hepatosis and moderate oedema of the brain. In both animals the brain oedema was particularly noticeable in the medulla oblongata. The mycotoxin fumonisin B1 was extracted and purified from the culture material of F. moniliforme MRC, 826 which contained appr...
O'Sullivan JD, Allworth AM, Paterson DL, Snow TM, Boots R, Gleeson LJ, Gould AR, Hyatt AD, Bradfield J.In September, 1994, an outbreak of severe respiratory disease affected 18 horses, their trainer, and a stablehand in Queensland, Australia. Fourteen horses and one human being died. A novel virus was isolated from those affected and named equine morbillivirus (EMV). We report a case of encephalitis caused by this virus. Results: A 35-year-old man from Queensland had a brief aseptic meningitic illness in August, 1994, shortly after caring for two horses that died from EMV infection and then assisting at their necropsies. He then suffered severe encephalitis 13 months later, characterised by unc...
Mansfield KL, Hernández-Triana LM, Banyard AC, Fooks AR, Johnson N.Japanese encephalitis virus (JEV) is a significant cause of neurological disease in humans throughout Asia causing an estimated 70,000 human cases each year with approximately 10,000 fatalities. The virus contains a positive sense RNA genome within a host-derived membrane and is classified within the family Flaviviridae. Like many flaviviruses, it is transmitted by mosquitoes, particularly those of the genus Culex in a natural cycle involving birds and some livestock species. Spill-over into domestic animals results in a spectrum of disease ranging from asymptomatic infection in some species t...
Nugent J, Birch-Machin I, Smith KC, Mumford JA, Swann Z, Newton JR, Bowden RJ, Allen GP, Davis-Poynter N.Equid herpesvirus 1 (EHV-1) can cause a wide spectrum of diseases ranging from inapparent respiratory infection to the induction of abortion and, in extreme cases, neurological disease resulting in paralysis and ultimately death. It has been suggested that distinct strains of EHV-1 that differ in pathogenic capacity circulate in the field. In order to investigate this hypothesis, it was necessary to identify genetic markers that allow subgroups of related strains to be identified. We have determined all of the genetic differences between a neuropathogenic strain (Ab4) and a nonneuropathogenic ...
Murray KO, Mertens E, Despres P.Zoonotic West Nile virus (WNV) circulates in natural transmission cycles involving certain mosquitoes and birds, horses, humans, and a range of other vertebrates are incidental hosts. Clinical infections in humans can range in severity from uncomplicated WNV fever to fatal meningoencephalitis. Since its introduction to the Western Hemisphere in 1999, WNV had spread across North America, Central and South America and the Caribbean, although the vast majority of severe human cases have occurred in the United States of America (USA) and Canada. By 2002-2003, the WNV outbreaks have involved thousa...
Autorino GL, Battisti A, Deubel V, Ferrari G, Forletta R, Giovannini A, Lelli R, Murri S, Scicluna MT.During the late summer of 1998, veterinary authorities in Tuscany, Italy, received reports of cases of neurologic disease among horses residing in a large wetland area located in the provinces of Florence and Pistoia. West Nile virus was isolated from two of the six horses that died or were euthanized. A retrospective epidemiologic study identified 14 clinical neurologic cases that occurred from August 20 to October 6 (attack rate of 2.8%). A serologic survey conducted over a 700-km2 area in stables with and without apparent clinical cases confirmed a wider spread of the infection, with an ove...
Kellerman TS, Marasas WF, Thiel PG, Gelderblom WC, Cawood M, Coetzer JA.Leukoencephalomalacia (LEM) was induced by the oral administration of fumonisin B1 (FB1) to 2 horses: a filly received 59.5 mg/kg of a 50% preparation of FB1, administered in 21 doses of 1.25-4 mg/kg over 33 days; a colt, 44.3 mg/kg of 95% pure FB1 in 20 doses of 1-4 mg/kg in 29 days. Both animals developed nervous signs such as apathy, changes in temperament, inco-ordination, walking into objects, and one showed paralysis of the lips and tongue. Characteristic lesions of LEM were present in the brains. These trials proved conclusively that FB1 can induce LEM in horses.
Morales MA, Barrandeguy M, Fabbri C, Garcia JB, Vissani A, Trono K, Gutierrez G, Pigretti S, Menchaca H, Garrido N, Taylor N, Fernandez F, Levis S....West Nile virus (WNV) was isolated from the brains of 3 horses that died from encephalitis in February 2006. The horses were from different farms in central Argentina and had not traveled outside the country. This is the first isolation of WNV in South America.
Gosztonyi G, Ludwig H.Natural BD is a nonpurulent acute/subacute encephalitis of horses and sheep with a propensity to involve the olfactory and limbic systems, and the brain stem. The inflammation is concentrated primarily in the gray matter, but subcortical white matter may also be affected. Experimental BD can be produced in a series of animals from birds to primates. The neuropathology after experimental infection is similar to that in natural disease but the inflammatory changes are more diffuse. In the rat and mouse, a persistent/tolerant infection can also be induced, in which inflammatory changes are conspi...
Suen WW, Prow NA, Hall RA, Bielefeldt-Ohmann H.West Nile virus (WNV) is an important emerging neurotropic virus, responsible for increasingly severe encephalitis outbreaks in humans and horses worldwide. However, the mechanism by which the virus gains entry to the brain (neuroinvasion) remains poorly understood. Hypotheses of hematogenous and transneural entry have been proposed for WNV neuroinvasion, which revolve mainly around the concepts of blood-brain barrier (BBB) disruption and retrograde axonal transport, respectively. However, an over‑representation of in vitro studies without adequate in vivo validation continues to obscure our...
Li L, Giannitti F, Low J, Keyes C, Ullmann LS, Deng X, Aleman M, Pesavento PA, Pusterla N, Delwart E.Metagenomics was used to characterize viral genomes in clinical specimens of horses with various organ-specific diseases of unknown aetiology. A novel parvovirus as well as a previously described hepacivirus closely related to human hepatitis C virus and equid herpesvirus 2 were identified in the cerebrospinal fluid of horses with neurological signs. Four co-infecting picobirnaviruses, including an unusual genome with fused RNA segments, and a divergent anellovirus were found in the plasma of two febrile horses. A novel cyclovirus genome was characterized from the nasal secretion of another fe...
Pérez DR, Damberger FF, Wüthrich K.The NMR structure of the horse (Equus caballus) cellular prion protein at 25 degrees C exhibits the typical PrP(C) [cellular form of prion protein (PrP)] global architecture, but in contrast to most other mammalian PrP(C)s, it contains a well-structured loop connecting the beta2 strand with the alpha2 helix. Comparison with designed variants of the mouse prion protein resulted in the identification of a single amino acid exchange within the loop, D167S, which correlates with the high structural order of this loop in the solution structure at 25 degrees C and is unique to the PrP sequences of e...
Cantile C, Di Guardo G, Eleni C, Arispici M.West Nile (WN) virus infection is a mosquito-borne flavivirosis endemic in Africa and Asia. Clinical disease is usually rare and mild and only in a few cases the infection causes encephalomyelitis in horses, fever and meningoencephalitis in man. We report here the clinical and pathological findings in an epidemic of the disease involving 14 horses from Tuscany, Italy. All cases were observed from August to October 1998. Affected horses showed ataxia, weakness paresis of the hindlimbs and, in 6 cases, there was paraparesis progressing to tetraplegia and recumbency within 2 to 9 days. Eight anim...
Beck C, Desprès P, Paulous S, Vanhomwegen J, Lowenski S, Nowotny N, Durand B, Garnier A, Blaise-Boisseau S, Guitton E, Yamanaka T, Zientara S....West Nile virus (WNV), Japanese encephalitis virus (JEV), and tick-borne encephalitis virus (TBEV) are flaviviruses responsible for severe neuroinvasive infections in humans and horses. The confirmation of flavivirus infections is mostly based on rapid serological tests such as enzyme-linked immunosorbent assays (ELISAs). These tests suffer from poor specificity, mainly due to antigenic cross-reactivity among flavivirus members. Robust diagnosis therefore needs to be validated through virus neutralisation tests (VNTs) which are time-consuming and require BSL3 facilities. The flavivirus envelop...
Field H, Schaaf K, Kung N, Simon C, Waltisbuhl D, Hobert H, Moore F, Middleton D, Crook A, Smith G, Daniels P, Glanville R, Lovell D.To determine the epidemiologic and clinical features of a 2008 outbreak of Hendra virus infection in a veterinary clinic in Australia, we investigated the equine case-series. Four of 5 infected horses died, as did 1 of 2 infected staff members. Clinical manifestation in horses was predominantly neurologic. Preclinical transmission appears likely.
Venter M, Human S, Zaayman D, Gerdes GH, Williams J, Steyl J, Leman PA, Paweska JT, Setzkorn H, Rous G, Murray S, Parker R, Donnellan C, Swanepoel R.Serologic evidence suggests that West Nile virus (WNV) is widely distributed in horses in southern Africa. However, because few neurologic cases have been reported, endemic lineage 2 strains were postulated to be nonpathogenic in horses. Recent evidence suggests that highly neuroinvasive lineage 2 strains exist in humans and mice. To determine whether neurologic cases are being missed in South Africa, we tested 80 serum or brain specimens from horses with unexplained fever (n = 48) and/or neurologic signs (n = 32) for WNV. From March 2007 through June 2008, using reverse transcription-PCR (RT-...
Brooks SA, Gabreski N, Miller D, Brisbin A, Brown HE, Streeter C, Mezey J, Cook D, Antczak DF.Lavender Foal Syndrome (LFS) is a lethal inherited disease of horses with a suspected autosomal recessive mode of inheritance. LFS has been primarily diagnosed in a subgroup of the Arabian breed, the Egyptian Arabian horse. The condition is characterized by multiple neurological abnormalities and a dilute coat color. Candidate genes based on comparative phenotypes in mice and humans include the ras-associated protein RAB27a (RAB27A) and myosin Va (MYO5A). Here we report mapping of the locus responsible for LFS using a small set of 36 horses segregating for LFS. These horses were genotyped usin...
Venter M, Swanepoel R.West Nile virus (WNV) is widely distributed in South Africa, but since a few cases of neurological disease have been reported from this region, endemic lineage 2 strains were postulated to be of low virulence. Several cases of nonfatal encephalitis in humans as well as fatal cases in a foal, dog, and ostrich chicks have, however, been associated with lineage 2 WNV in South Africa. The pathogenesis of lineage 2 WNV strains was investigated using mouse neuroinvasive experiments, gene expression experiments, and genome sequence comparisons which indicated that lineage 2 strains that are highly pa...
Dubey JP, Lindsay DS, Saville WJ, Reed SM, Granstrom DE, Speer CA.Equine protozoal myeloencephalitis (EPM) is a serious neurological disease of horses in the Americas. The protozoan most commonly associated with EPM is Sarcocystis neurona. The complete life cycle of S. neurona is unknown, including its natural intermediate host that harbors its sarcocyst. Opossums (Didelphis virginiana, Didelphis albiventris) are its definitive hosts. Horses are considered its aberrant hosts because only schizonts and merozoites (no sarcocysts) are found in horses. EPM-like disease occurs in a variety of mammals including cats, mink, raccoons, skunks, Pacific harbor seals, p...
Cantile C, Del Piero F, Di Guardo G, Arispici M.The pathologic and peroxidase immunohistochemical features of West Nile flavivirus (WNV) infection were compared in four horses from the northeastern United States and six horses from central Italy. In all 10 animals, there were mild to severe polioencephalomyelitis with small T lymphocyte and lesser macrophage perivascular infiltrate, multifocal glial nodules, neutrophils, and occasional neuronophagia. Perivascular hemorrhages, also noted macroscopically in two animals, were observed in 50% of the horses. In the four American horses, lesions extended from the basal nuclei through the brain st...
Henninger RW, Reed SM, Saville WJ, Allen GP, Hass GF, Kohn CW, Sofaly C.Equine herpesvirus type 1 (EHV-1) infection causes neurologic disease in horses. However, risk factors for the disease and long-term prognosis are poorly characterized. Objective: There are identifiable risk factors for equine herpes-1 myeloencephalopathy. Methods: The entire population of 135 horses housed within the equestrian facility. Methods: A descriptive study investigated the clinical, serologic, virologic, and management aspects of an outbreak of EHV-1 myeloencephalopathy. Results: Out of 135 horses at the facility, 117 displayed signs of EHV-1 infection. Forty-six horses developed ne...
Allen GP.To identify risk factors associated with development of clinical neurologic signs in horses exposed to equine herpesvirus-1 (EHV-1). Methods: 36 adult horses. Methods: Blood samples collected before and after challenge inoculation with nonneuropathogenic or neuropathogenic EHV-1 were analyzed for leukocyte-associated viremia, serum neutralizing antibody, and EHV-1-specific cytotoxic T-lymphocyte precursors (CTLPs). Associations between variables and neurologic disease and correlations between age category or breed and development of neurologic disease were examined. Results: 9 horses developed...
Goehring LS, van Winden SC, van Maanen C, Sloet van Oldruitenborgh-Oosterbaan MM.Equine herpesvirus type 1(EHV-1)-associated myeloencephalopathy (EHM) is a rare disease affecting the central nervous system and, in particular, the spinal cord of horses. Epidemiologic data are limited, and usually are restricted to the description of a single outbreak. During an observational period of 4 years, we evaluated 9 outbreaks of EHM in The Netherlands. A risk factor analysis was done on the data from 6 outbreaks. Findings were: regular appearance of EHM outbreaks in The Netherlands (2-3/y); strong association of EHM with season; and risk factors, such as breed, sex, age, and fever....
Perkins GA, Goodman LB, Tsujimura K, Van de Walle GR, Kim SG, Dubovi EJ, Osterrieder N.A single nucleotide polymorphism in the equine herpesvirus 1 (EHV-1) DNA polymerase gene (ORF30 A(2254) to G) has been associated with clinical signs of equine herpes myeloencephalopathy (EHM). The purpose of our study was to determine the odds ratio for this genetic marker and EHM using a panel of field isolates from North America collected over the past twenty-three years. EHV-1 isolates cultured at the Cornell University Animal Health Diagnostic Laboratory from 1984 to 2007 were retrieved along with their clinical histories. DNA was extracted from these EHV-1 cultures and allelic discrimina...
Donadieu E, Bahuon C, Lowenski S, Zientara S, Coulpier M, Lecollinet S.West Nile virus (WNV) is a neurotropic flavivirus that cycles between mosquitoes and birds but that can also infect humans, horses, and other vertebrate animals. In most humans, WNV infection remains subclinical. However, 20%-40% of those infected may develop WNV disease, with symptoms ranging from fever to meningoencephalitis. A large variety of WNV strains have been described worldwide. Based on their genetic differences, they have been classified into eight lineages; the pathogenic strains belong to lineages 1 and 2. Ten years ago, Beasley et al. (2002) found that dramatic differences exist...
Beck C, Leparc Goffart I, Franke F, Gonzalez G, Dumarest M, Lowenski S, Blanchard Y, Lucas P, Lamballerie X, Grard G, Durand GA, Zientara S....Since 2015, annual West Nile virus (WNV) outbreaks of varying intensities have been reported in France. Recent intensification of enzootic WNV circulation was observed in the South of France with most horse cases detected in 2015 ( = 49), 2018 ( = 13), and 2019 ( = 13). A WNV lineage 1 strain was isolated from a horse suffering from West Nile neuro-invasive disease (WNND) during the 2015 episode in the Camargue area. A breaking point in WNV epidemiology was achieved in 2018, when WNV lineage 2 emerged in Southeastern areas. This virus most probably originated from WNV spread from Northern Ital...
