Neurological Disease: What the Research Says
Evidence from 26 peer-reviewed studies
What Professionals Should Know
- •Currently available pharmacologic treatments show minimal evidence of benefit for preventing or reducing EHV-1 disease severity in horses; focus should remain on biosecurity and supportive care
- •Veterinarians should counsel horse owners that no pharmacologic therapy has demonstrated clear clinical efficacy for EHV-1, and discuss evidence-based management strategies instead
- •The lack of effective pharmacologic interventions highlights the importance of vaccination programs and infection control measures as primary prevention strategies
- •Motion capture gait analysis provides objective measurement of ataxia when subjective clinical assessment is unreliable, particularly for mild cases
- •Blindfolding during neurological examination exacerbates movement variability in ataxic horses, making clinical signs more apparent and improving diagnostic discrimination
- •Distal limb kinematics (particularly hoof displacement) are more sensitive indicators of ataxia than proximal markers when assessed with motion capture
- •Age and severity of clinical pathology abnormalities are critical prognostic indicators when counseling owners on emergency admission outcomes; foals and geriatric horses require particularly guarded prognosis discussions
- •Abnormal peritoneal fluid and coagulopathy findings warrant very poor prognostic estimates (71% and 63% mortality), while straightforward orthopedic injuries carry excellent survival prospects, aiding case triage and client communication
- •The high mortality associated with intranasal oxygen therapy likely reflects underlying severe respiratory compromise rather than iatrogenic harm, emphasizing the importance of addressing underlying disease pathology rather than relying on supportive care alone
- •South African horse practitioners should recognize that WNV exposure is common but benign in local populations, contrasting with the neurological disease risk in other geographic regions
- •Young horses showing WNV seropositivity without clinical signs may simply reflect endemic exposure rather than active disease requiring treatment
- •Awareness of geographic variation in WNV pathogenicity is important when considering disease risk and diagnostic interpretation in international horse movements
- •This mouse model provides a valuable tool for understanding how SHUV causes neurological disease in horses and cattle, potentially informing future diagnostic and preventive strategies
- •Identification of target cells (neurons, astrocytes, immune cells) helps explain the neurological manifestations seen in naturally infected horses and cattle
- •The zoonotic potential of SHUV warrants awareness among equine and livestock practitioners in endemic regions (Africa, Middle East, Israel)
- •Clinicians in Mediterranean regions should maintain awareness of WNV-L1 as a differential diagnosis for acute neurological disease in horses, even in areas with apparent absence of disease for years
- •Expect the possibility of silent viral circulation between obvious clinical cases; surveillance programs should continue even during apparent eclipse periods to detect re-emergence early
- •Climate change may expand geographic range and alter seasonal patterns of WNV; biosecurity measures against insect vectors remain important despite variable disease activity
- •This mouse model demonstrates the mechanisms of EHV-1 neuropathology but has limited direct application to equine practice; findings are primarily relevant for researchers studying viral pathogenesis
- •Understanding chemokine and apoptosis markers in EHV-1 CNS infection may eventually inform therapeutic targets, though clinical translation remains distant
- •The study characterizes two highly neurovirulent EHV-1 strains that could be concerning if they represent field-relevant virus variants affecting horses
- •Genetic testing may eventually help identify horses at higher risk of developing EHM following EHV-1 infection, informing management and biosecurity decisions
- •Understanding host genetic factors could support selective breeding to reduce EHM susceptibility in horse populations
- •Not all EHV-1 infected horses develop myeloencephalopathy; genetic screening may help predict which individuals require more intensive monitoring
- •Even well-managed stud farms with good biosecurity can experience EHV-1 abortion outbreaks, necessitating vigilant surveillance and rapid response protocols
- •EHV-1 should be considered in differential diagnosis for any abortion, respiratory signs, neonatal death, or neurological disease outbreaks on equine properties
- •Implementation of outbreak management and prevention strategies specific to EHV-1 is critical for stud farm operations
- •Levetiracetam may offer a safer and more cost-effective anticonvulsant alternative for neonatal foals compared to current options
- •Dosing recommendations from adult horses cannot be directly applied to neonatal foals due to pharmacokinetic differences
- •Further pharmacokinetic studies in neonatal foals are needed to establish appropriate dosing protocols before clinical use
- •EHV-1-induced platelet activation and thrombosis provides a mechanistic explanation for abortion and neurological complications in infected horses, though this in vitro finding requires validation in clinical cases
- •Understanding the tissue factor-dependent pathway of platelet activation may inform future therapeutic strategies targeting thrombotic complications in EHV-1 outbreaks
- •This is laboratory research; clinicians should continue following established EHV-1 management protocols while this mechanism is further studied
- •High viral loads (especially in nasal secretions) detected by PCR appear to be a poor prognostic indicator in EHM cases and may warrant aggressive intervention or case counseling about prognosis
- •Initial neurological grade alone should not be used to predict outcome; viral load quantification may provide additional prognostic information
- •All affected horses in this series were infected with the D752 genotype of EHV-1; practitioners should consider viral genotyping if available for prognostic or epidemiological purposes
- •Bunyamwera virus should be considered in the differential diagnosis for equine encephalitis and abortion cases in Argentina and potentially other regions
- •Clinicians should maintain awareness of emerging viral pathogens affecting equine populations, particularly those with neurological presentations
- •Brain and spleen tissue sampling may be indicated for suspected viral encephalitis cases to enable pathogen identification
- •WNV should be included in differential diagnosis for horses presenting with neurological signs, particularly those affecting the brainstem and spinal cord
- •Multiple diagnostic methods (immunohistochemistry, in situ hybridization, and serology) may be needed for definitive WNV diagnosis in affected horses
- •Awareness of WNV clinical presentation is important for early recognition and appropriate biosecurity measures on affected premises
- •Atlanto-occipital CSF collection can be performed on standing horses using ultrasound guidance and sedation alone, avoiding the need for general anaesthesia in horses with severe neurological signs or where anaesthesia is contraindicated
- •Proper safety measures and close observation remain essential, as this is a novel application with limited evidence in ataxic horses
- •Further research on larger numbers of ataxic horses is needed before recommending this as standard alternative to anaesthetised collection
- •Japanese encephalitis should be considered in the differential diagnosis of neurological disease in adult cattle, not just young stock, particularly in endemic regions
- •JEV infection can present with nonsuppurative encephalomyelitis; diagnostic confirmation requires virus isolation, antigen detection, and serological testing together
- •Geographic surveillance of JEV strains is important as related genotypes have been identified in specific prefectures over multiple years
- •Identical EHV-1 strains can present very different clinical pictures between herds; breed composition should be considered when assessing outbreak severity and likely outcomes
- •Serologically negative imported horses can still be EHV-1 carriers and vectors; quarantine and pre-import testing protocols must be enforced regardless of health certificates
- •Clinically healthy stallions can transmit EHV-1 between farms; use extreme caution with breeding stock movements and consider epidemiological history of source herds during breeding season outbreaks
- •EHV-9 is a neurotropic virus with multiple routes of potential infection; respiratory exposure poses highest risk for rapid neurological disease onset
- •The variable clinical presentation based on exposure route suggests that clinical signs and severity of EHV-9 may depend on how horses are initially exposed to the virus
- •Understanding that virus can reach the brain via non-respiratory pathways may inform biosecurity protocols for managing infected animals and preventing nervous system involvement
- •Polyneuritis equi appears to involve T-cell mediated autoimmune attack on myelin, which may inform future immunomodulatory treatment approaches
- •Local antibody production suggests both cellular and humoral immune components are involved in disease pathogenesis
- •This is a rare condition requiring specialist investigation; prospective studies are needed before treatment recommendations can be established
- •EHV-1 can transmit across species barriers and cause fatal neurological disease in non-equine animals; biosecurity protocols should segregate equids from other species in mixed-species facilities
- •Clinical signs of EHV-1 encephalitis (incoordination, stumbling, neurological dysfunction) may occur in non-equine species but may not be immediately recognized as EHV-1-related
- •Zoo and exotic animal facilities housing equids should implement strict isolation procedures and serological screening to prevent cross-species transmission events
- •Add Sida carpinifolia to differential diagnosis for horses with progressive neurological disease, especially in southern Brazil and regions with this plant
- •If ponies are introduced to new pasture and develop stiff gait, tremors, and abdominal pain within 2-3 weeks, consider plant toxicosis and inspect for Sida carpinifolia infestation
- •No specific treatment mentioned; prevention through pasture management and avoiding introduction to contaminated paddocks is essential
- •EHV-1 neurological disease carries a grave prognosis for recumbent horses; even horses that survive intensive care often develop permanent neurological deficits requiring long-term euthanasia decisions
- •Introduction of a single purchased horse can trigger rapid spread of neurological EHV-1 through a closed population within 3 weeks; vigilant quarantine protocols are critical for riding school biosecurity
- •Diagnosis requires strategic sampling of febrile in-contact horses with both virological (nasal swabs for isolation) and serological testing; gG-specific ELISA is more reliable than older serological methods for confirming EHV-1 involvement
- •HVE-1 myeloencephalitis is circulating in the Brazilian Amazon and should be considered in differential diagnosis for equine neurological disease presenting with progressive paresis and incoordination
- •Early treatment with vitamin B1 combined with anti-inflammatory agents (dexamethasone or flunixim meglumine) is associated with recovery within 8 days
- •Practitioners in endemic regions should maintain biosecurity protocols and consider HVE-1 serology/PCR testing for horses with acute onset neurological signs, particularly hind limb dysfunction
- •Equine practitioners should recognize that horses are susceptible to natural Nipah virus infection and implement biosecurity protocols to prevent exposure to potentially infected animals, particularly in endemic regions
- •Maintain awareness of zoonotic transmission risk and report suspected cases to veterinary authorities, as the disease presents with respiratory and neurological signs that may overlap with other equine conditions
- •Monitor for emerging spillover events in your region, particularly in areas with bat populations and mixed animal farming operations, as climate and anthropogenic changes may increase disease transmission risk
- •EHV-1 environmental contamination in typical horse housing is difficult to eliminate completely, requiring consideration of the virus's environmental persistence characteristics
- •Understanding that the viral envelope is vulnerable to environmental conditions allows practitioners to optimize stable management and disinfection protocols
- •Housing design and material selection (sealed vs. unsealed wood, bedding type) should be considered in EHV-1 prevention and control strategies
- •Syndromic surveillance data (respiratory and neurological cases) can be statistically evaluated using likelihood ratios to support objective outbreak detection decisions rather than relying on subjective interpretation
- •This framework helps distinguish between natural variation in disease reporting and evidence of a true outbreak, reducing false alarms and improving resource allocation
- •Practitioners can integrate multiple data sources (surveillance, models, risk assessments) transparently into disease outbreak response decisions
Key Research Findings
Of 7009 identified studies, only 9 met inclusion criteria for in vivo therapeutic interventions in horses with EHV-1
Interventions tested included valacyclovir, small interfering RNAs, Parapoxvirus ovis-based immunomodulator, human alpha interferon, herbal supplement, cytosine analog, and heparin
Most studies reported no benefit or minimal efficacy for any tested intervention in preventing or treating EHV-1-associated disease
Risk of bias was moderate to high across included studies with small sample sizes and evidence ranging from randomized controlled trials to observational trials
Coefficient of variation in maximum vertical displacement of pelvic and thoracic distal limbs provided good diagnostic yield for ataxia grade ≥2
Thoracic hoof marker achieved AUC of 0.81 with 64% sensitivity and 90% specificity in normal conditions
Blindfolding increased diagnostic accuracy with hoof marker AUC improving to 0.89 with 82% sensitivity and 90% specificity
Motion capture can objectively assess ataxia severity when clinical agreement among experienced assessors is poor
Overall death rate in equine emergency admissions was 24%, with foals (34%) and geriatric horses (40%) having significantly higher mortality than mature horses (21%)
Neurological (46%) and neonatal (41%) presentations had the highest death rates, while ophthalmological (5%) and trauma/skin (13%) cases had the lowest
Critical pathology abnormalities including abnormal peritoneal fluid (71%), coagulopathy (63%), acid-base abnormalities (52%), and hypoxia/hypercapnia (48%) were strongly associated with poor outcomes
Procedural interventions showed variable outcomes: intranasal oxygen therapy (57% death rate) and plasma transfusion (34%) were associated with high mortality, while joint lavage (4%) and laceration repair (0%) had excellent survival rates
Approximately 11% of South African Thoroughbred yearlings seroconverted to WNV over a 12-month period
75% of dams showed WNV seropositivity, indicating high prevalence of exposure in breeding populations
No neurological disease was observed in any naturally infected horses or in 2 horses experimentally inoculated with a South African WNV isolate
Evidence Base
Pharmacologic interventions for the treatment of equine herpesvirus-1 in domesticated horses: A systematic review.
Goehring Lutz, Dorman David C, Osterrieder Klaus et al. (2024) — Journal of veterinary internal medicine
Kinematic discrimination of ataxia in horses is facilitated by blindfolding.
Olsen E, FouchÉ N, Jordan H et al. (2018) — Equine veterinary journal
Short-term outcome of equine emergency admissions at a university referral hospital.
Southwood L L, Dolente B A, Lindborg S et al. (2009) — Equine veterinary journal
West Nile virus infection of Thoroughbred horses in South Africa (2000-2001).
Guthrie A J, Howell P G, Gardner I A et al. (2003) — Equine veterinary journal
Characterization of experimental Shuni virus infection in the mouse.
Breithaupt Angele, Sick Franziska, Golender Natalia et al. (2023) — Veterinary pathology
Reoccurrence of West Nile virus lineage 1 after 2-year decline: first equine outbreak in Campania region.
de Martinis Claudio, Cardillo Lorena, Pesce Federica et al. (2023) — Frontiers in veterinary science
Pathogenesis of Equid Alphaherpesvirus 1 Infection in the Central Nervous System of Mice.
Mesquita Leonardo P, Costa Rafael C, Mesquita Laís L R et al. (2021) — Veterinary pathology
Genome-wide association study for host genetic factors associated with equine herpesvirus type-1 induced myeloencephalopathy.
Dunuwille Wangisa M B, YousefiMashouf Navid, Balasuriya Udeni B R et al. (2020) — Equine veterinary journal
Outbreak of equid herpesvirus 1 abortions at the Arabian stud in Poland.
Stasiak Karol, Dunowska Magdalena, Rola Jerzy (2020) — BMC veterinary research
Pharmacokinetics of the anticonvulsant levetiracetam in neonatal foals.
MacDonald K D, Hart K A, Davis J L et al. (2018) — Equine veterinary journal
Equid herpesvirus type 1 activates platelets.
Stokol Tracy, Yeo Wee Ming, Burnett Deborah et al. (2015) — PloS one
Quantitative molecular viral loads in 7 horses with naturally occurring equine herpesvirus-1 infection.
Estell K E, Dawson D R, Magdesian K G et al. (2015) — Equine veterinary journal
First isolation of Bunyamwera virus (Bunyaviridae family) from horses with neurological disease and an abortion in Argentina.
Tauro Laura B, Rivarola Maria E, Lucca Eduardo et al. (2015) — Veterinary journal (London, England : 1997)
West Nile Virus Infection in Horses: Detection by Immunohistochemistry, In Situ Hybridization, and ELISA.
Toplu N, Oğuzoğlu T Ç, Ural K et al. (2015) — Veterinary pathology
Ultrasound-guided atlanto-occipital puncture for cerebrospinal fluid analysis on the standing horse.
Depecker M, Bizon-Mercier C, Couroucé-Malblanc A (2014) — The Veterinary record
Japanese encephalitis in a 114-month-old cow: pathological investigation of the affected cow and genetic characterization of Japanese encephalitis virus isolate.
Kako Naomi, Suzuki Seiji, Sugie Norie et al. (2014) — BMC veterinary research
Two outbreaks of neuropathogenic equine herpesvirus type 1 with breed-dependent clinical signs.
Barbić L, Lojkić I, Stevanović V et al. (2012) — The Veterinary record
Study on the infectivity of equine herpesvirus 9 (EHV-9) by different routes of inoculation in hamsters.
El-Habashi N, Murakami M, El-Nahass E et al. (2011) — Veterinary pathology
The composition of the inflammatory infiltrate in three cases of polyneuritis equi.
van Galen G, Cassart D, Sandersen C et al. (2008) — Equine veterinary journal
Fatal herpesvirus encephalitis in a reticulated giraffe (Giraffa camelopardalis reticulata).
Hoenerhoff M J, Janovitz E B, Richman L K et al. (2006) — Veterinary pathology
Show 6 more references
Lysosomal storage disease in Sida carpinifolia toxicosis: an induced mannosidosis in horses.
Loretti A P, Colodel E M, Gimeno E J et al. (2003) — Equine veterinary journal
Neurological disease associated with EHV-1-infection in a riding school: clinical and virological characteristics.
van Maanen C, Sloet van Oldruitenborgh-Oosterbaan M M, Damen E A et al. (2001) — Equine veterinary journal
Equine Herpesvirus Type 1 Myeloencephalitis in the Brazilian Amazon.
Barbosa José Diomedes, Lins André de Medeiros Costa, Bomjardim Henrique Dos Anjos et al. (2022) — Animals : an open access journal from MDPI
Nipah Virus Disease: Epidemiological, Clinical, Diagnostic and Legislative Aspects of This Unpredictable Emerging Zoonosis.
Bruno Luigi, Nappo Maria Anna, Ferrari Luca et al. (2022) — Animals : an open access journal from MDPI
Environmental persistence of equid herpesvirus type-1.
Saklou Nadia T, Burgess Brandy A, Ashton Laura V et al. (2021) — Equine veterinary journal
Using Bayes' rule to define the value of evidence from syndromic surveillance.
Andersson Mats Gunnar, Faverjon Céline, Vial Flavie et al. (2014) — PloS one