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A 3-year-old American Saddlebred gelding presented for progressive tetraparesis, ataxia, and cervical hyperaesthesia. Radiographic myelography identified spinal cord compression at C6-7 in neutral, extended, and flexed positions and at C4-5 in the flexed position. CT myelography and postmortem MRI identified severe vertebral canal stenosis/compression at C6-7. MRI further identified severe intervertebral disc herniation at C6-7 with intramedullary changes. Disc protrusion was confirmed macroscopically at postmortem. Lesions consistent with compressive myelopathy were confirmed microscopically at C6-7. This is the first report of equine disc protrusion and myelocompression confirmed by multiple advanced imaging modalities and postmortem examination., (© 2024 American College of Veterinary Radiology.)

Background: Equine neuroaxonal dystrophy/degenerative myeloencephalopathy (eNAD/EDM) is a neurodegenerative disease that primarily affects young, genetically predisposed horses that are deficient in vitamin E. Equine NAD/EDM has not previously been documented in Gypsy Vanner horses (GVs)., Objectives: To evaluate: (1) the clinical phenotype, blood vitamin E concentrations before and after supplementation and pedigree in a cohort of GV horses with a high prevalence of neurologic disease suspicious for eNAD/EDM and (2) to confirm eNAD/EDM in GVs through postmortem evaluation., Animals: Twenty-six GVs from 1 farm in California and 2 cases from the Midwestern U.S., Methods: Prospective observational study on Californian horses; all 26 GVs underwent neurologic examination. Pre-supplementation blood vitamin E concentration was assessed in 17- GVs. Twenty-three were supplemented orally with 10 IU/kg of liquid RRR-alpha-tocopherol once daily for 28 days. Vitamin E concentration was measured in 23 GVs after supplementation, of which 15 (65%) had pre-supplementation measurements. Two clinically affected GVs from California and the 2 Midwestern cases had necropsy confirmation of eNAD/EDM., Results: Pre-supplementation blood vitamin E concentration was ≤2.0 μg/mL in 16/17 (94%) of GVs from California. Post-supplementation concentration varied, with a median of 3.39 μg/mL (range, 1.23-13.87 μg/mL), but only 12/23 (52%) were normal (≥3.0 μg/mL). Normalization of vitamin E was significantly associated with increasing age (P = .02). Euthanized horses (n = 4) had eNAD/EDM confirmed at necropsy., Conclusions and Clinical Importance: GVs could have a genetic predisposition to eNAD/EDM. Vitamin E supplementation should be considered and monitored in young GVs., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Cervical vertebral compressive myelopathy (CVCM) and equine neuroaxonal dystrophy/degenerative myeloencephalopathy (eNAD/EDM) are leading causes of spinal ataxia in horses. The conditions can be difficult to differentiate, and there is currently no diagnostic modality that offers a definitive antemortem diagnosis., Objective: Evaluate novel proteomic techniques and machine learning algorithms to predict biomarkers that can aid in the antemortem diagnosis of noninfectious spinal ataxia in horses., Animals: Banked serum and cerebrospinal fluid (CSF) samples from necropsy-confirmed adult eNAD/EDM (n = 47) and CVCM (n = 25) horses and neurologically normal adult horses (n = 45)., Methods: . A subset of serum and CSF samples from eNAD/EDM (n = 5) and normal (n = 5) horses was used to evaluate the proximity extension assay (PEA). All samples were assayed by PEA for 368 neurologically relevant proteins. Data were analyzed using machine learning algorithms to define potential diagnostic biomarkers., Results: Of the 368 proteins, 84 were detected in CSF and 146 in serum. Eighteen of 84 proteins in CSF and 30/146 in serum were differentially abundant among the 3 groups, after correction for multiple testing. Modeling indicated that a 2-protein test using CSF had the highest accuracy for discriminating among all 3 groups. Cerebrospinal fluid R-spondin 1 (RSPO1) and neurofilament-light (NEFL), in parallel, predicted normal horses with an accuracy of 87.18%, CVCM with 84.62%, and eNAD/EDM with 73.5%., Main Limitations: Cross-species platform. Uneven sample size., Conclusions and Clinical Importance: Proximity extension assay technology allows for rapid screening of equine biologic matrices for potential protein biomarkers. Machine learning analysis allows for unbiased selection of highly accurate biomarkers from high-dimensional data., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: High-serum γ-Glutamyl Transferase (GGT) activity has been associated with and thought to be a marker of maladaptation to training and possibly poor performance in racehorses, but the cause is unknown., Objectives: To investigate possible metabolic and infectious causes for the high GGT syndrome., Study Design: Pilot case-control study and nested case-control study., Methods: The case-control study in 2017 included 16 horses (8 cases and 8 controls with median [range] serum GGT 82 [74-148] and 22 [19-28] IU/L, respectively) from the same stable. In 2018, similar testing was performed in a nested case-control study that identified 27 case (serum GGT 50 ≥ IU/L)-control pairs from three stables for further testing. Serum liver chemistries, selenium measurements, viral PCR and metabolomics were performed., Results: No differences were found in frequency of detection of viral RNA/DNA or copy numbers for equine hepacivirus (EqHV) and parvovirus-hepatitis (EqPV-H) between cases and controls. Mild increases in hepatocellular injury and cholestatic markers in case vs control horses suggested a degree of liver disease in a subset of cases. Metabolomic and individual bile acid testing showed differences in cases compared with controls, including increased abundance of pyroglutamic acid and taurine-conjugated bile acids, and reduced abundance of Vitamin B6. Selenium concentrations, although within or above the reference intervals, were also lower in case horses in both studies., Main Limitations: Observational study design did not allow us to make causal inferences., Conclusions: We conclude that high GGT syndrome is likely a complex metabolic disorder and that viral hepatitis was not identified as a cause for this syndrome in this cohort of racehorses. Our results support a contribution of oxidative stress and cholestasis in its pathophysiology., (© 2021 EVJ Ltd.)

Background: The diagnosis of equine protozoal myeloencephalitis (EPM) relies heavily on the clinical examination. The accurate identification of neurologic signs during a clinical examination is critical to the interpretation of laboratory results., Objective: To investigate the level of agreement between board-certified veterinary internists when performing neurologic examinations in horses., Animals: Ninety-seven horses admitted to the Veterinary Teaching Hospital at The Ohio State University from December 1997 to June 1998., Methods: A prospective epidemiologic research design was used. Horses enrolled in the study were examined by the internist responsible for care of the horse, and later by an internist who was not aware of the presenting complaint or other patient history. Data were analyzed by descriptive statistics, and kappa (K) statistics were calculated to assess interobserver agreement., Results: Ninety-seven horses were enrolled in the study. Overall, examiners, also referred to as observers, agreed that 60/97 (61.9%) were clinically abnormal, 21/97 (21.6%) were clinically normal, and the status of 16/97 (16.5%) of horses was contested. There was complete agreement among the examiners with regard to cranial nerve signs and involuntary movements. Disagreement involving severity of clinical signs occurred in 31 horses, and 25 of those horses (80.6%) were considered either normal or mildly affected by the primary observer. When examining the results of all paired clinical examinations for 11 different categories, there was wide variability in the results. When examiners rated the presence or absence of any neurologic abnormalities, lameness, or ataxia, the agreement among observers was either good or excellent for 80% of horses. When assessing truncal sway, the agreement among observers was good or excellent for 60% of the horses. When examining the horses for asymmetry of deficits, agreement was either good or excellent for 40% of the horses. Agreement among observers was excellent or good for only 20% of the horses when assessing muscle atrophy, spasticity (hypermetria), and overall assessment of the severity of neurologic abnormalities., Conclusions and Clinical Importance: This study underscores the subjectivity of the neurologic examination and demonstrates a reasonable level of agreement that may be achieved when different clinicians examine the same horse., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

There are rare published reports of atrial fibrillation (AF) in foals, all of which are associated with structural heart disease or within the adaptive period of newborns. This report describes a 3-month-old Thoroughbred filly with AF and a structurally normal heart on echocardiography. Medical cardioversion of the foal's AF was attempted with three 20mg/kg doses of quinidine sulfate therapy without success. Timed, transcutaneous, direct current cardioversion was successfully performed using adhesive patches on the midthorax in conjunction with intravenous procainamide at a total dose of 20mg/kg. A normal sinus rhythm was maintained through discharge from the hospital and at recheck 5 months after cardioversion. Transcutaneous direct current cardioversion presents a feasible alternative to quinidine sulfate or transvenous electrical cardioversion in young or lower body weight equids., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Equine protozoal myeloencephalitis (EPM) remains an important neurologic disease of horses. There are no pathognomonic clinical signs for the disease. Affected horses can have focal or multifocal central nervous system (CNS) disease. EPM can be difficult to diagnose antemortem. It is caused by either of 2 parasites, Sarcocystis neurona and Neospora hughesi, with much less known about N. hughesi. Although risk factors such as transport stress and breed and age correlations have been identified, biologic factors such as genetic predispositions of individual animals, and parasite-specific factors such as strain differences in virulence, remain largely undetermined. This consensus statement update presents current published knowledge of the parasite biology, host immune response, disease pathogenesis, epidemiology, and risk factors. Importantly, the statement provides recommendations for EPM diagnosis, treatment, and prevention., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Neonatal encephalopathy is the most common neurologic condition affecting newborn foals and shares similarities with perinatal asphyxia syndrome of human infants. In many cases of neonatal encephalopathy there is no obvious episode of acute or chronic hypoxia and other mechanisms likely play a role in the pathogenesis. Increased concentrations of neuroactive progestagens are found in affected foals; whether these molecules are protective, as has been suggested, or play a role in the pathogenesis is unknown. Neurologic diseases other than neonatal encephalopathy affect foals occasionally and should be considered when evaluating sick foals with clinical signs of neurologic dysfunction., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Skeletal lesions in the articular processes of cervical vertebrae C2 to C7 were compared between Thoroughbred horses with cervical stenotic myelopathy (17 males, 2 females; age, 6-50 months) and controls (6 males, 3 females; age, 9-67 months). Lesions identified by magnetic resonance imaging occurred with an increased frequency and severity in diseased horses and were not limited to sites of spinal cord compression. Lesions involved both the articular cartilage and trabecular bone and were further characterized using micro-computed tomography and histopathology. The most common histologic lesions included osteochondrosis, osseous cyst-like structures, fibrous tissue replacement of trabecular bone, retained cartilage matrix spicules, and osteosclerosis. Osseous cyst-like structures were interpreted to be true bone cysts given they were a closed cavity with a cellular lining that separated the cyst from surrounding bone. This is the first report of bone cysts in the cervical articular processes of horses with cervical stenotic myelopathy. The morphology and distribution of the lesions provide additional support for the previously proposed pathogenesis that developmental abnormalities with likely secondary biomechanical influences on the cervical spine contribute to equine cervical stenotic myelopathy., (© The Author(s) 2015.)

Reasons for Performing Study: To investigate and further characterise posture and movement characteristics during forward and backward walking in horses with shivering and acquired, bilateral stringhalt., Objectives: To characterise the movement of horses with shivering (also known as shivers) in comparison with control horses and horses with acquired bilateral stringhalt., Study Design: Qualitative video analysis of gait in horses., Methods: Owners' and authors' videos of horses with shivering or stringhalt and control horses walking forwards and backwards and manually lifting their limbs were examined subjectively to characterise hyperflexion, hyperextension and postural abnormalities of the hindlimbs. The pattern and timing of vertical displacement of a hindlimb over one stride unit was evaluated among control, shivering and stringhalt cases., Results: Gait patterns of shivering cases were characterised as follows: shivering-hyperextension (-HE, n = 13), in which horses subjectively showed hyperextension when backing and lifting the limb; shivering-hyperflexion (-HF, n = 27), in which horses showed hindlimb hyperflexion and abduction during backward walking; and shivering-forward hyperflexion (-FHF, n = 4), which resembled shivering-HF but included intermittent hyperflexion and abduction with forward walking. Horses with shivering-HF, shivering-FHF and stringhalt (n = 7) had a prolonged swing phase duration compared with control horses and horses with shivering-HE during backward walking. With the swing phase of forward walking, horses with stringhalt had a rapid ascent to adducted hyperflexion of the hindlimb, compared with a rapid descent of the hindlimb after abducted hyperflexion in horses with shivering-FHF., Conclusions: Shivering affects backward walking, with either HE or HF of hindlimbs, and can gradually progress to involve intermittent abducted hyperflexion during forward walking. Shivering-HF and shivering-FHF can look remarkably similar to acquired bilateral stringhalt during backward walking; however, stringhalt can be distinguished from shivering-HF by hyperflexion during forward walking and from shivering-FHF by an acute onset of a more consistent, rapidly ascending, hyperflexed, adducted hindlimb gait at a walk., (© 2014 EVJ Ltd.)

Reasons for Perfoming Study: Investigating the epidemiology of shivering in horses., Objectives: The purpose of this study was to characterise the signalment, clinical signs and management factors associated with shivering (also known as shivers), a relatively rare, poorly defined movement disorder in horses., Study Design: Web-based case series survey and case-control study., Methods: A Web-based survey was used to obtain information from owners, worldwide, who suspected that their horse had shivering. Survey respondents were asked to answer standardised questions and to provide a video of the horse. Authors reviewed the surveys and videos, and horses were diagnosed with shivering if they displayed normal forward walking, with difficulty during manual lifting of the hoof and backward walking due to hyperflexion or hyperextension of the pelvic limbs. Cases confirmed by video were designated 'confirmed shivering', while those with compatible clinical signs but lacking video confirmation were designated 'suspected shivering'. Owners of confirmed shivering horses were asked to provide information on 2 horses without signs of shivering (control group)., Results: Three hundred and five surveys and 70 videos were received; 27 horses were confirmed shivering (50 controls), 67 were suspected shivering and the rest had a variety of other movement disorders. Suspected shivering horses resembled confirmed shivering cases, except that the suspected shivering group contained fewer draught breeds and fewer horses with exercise intolerance. Confirmed shivering signs often began at <5 years of age and progressed in 74% of cases. Owner-reported additional clinical signs in confirmed cases included muscle twitching (85%), muscle atrophy (44%), reduced strength (33%) and exercise intolerance (33%). Shivering horses were significantly taller (confirmed shivering, mean ∼173 cm; control horses, ∼163 cm) with a higher male:female ratio (confirmed shivering, 3.2:1 vs. control, 1.7:1). No potential triggering factors or effective treatments were reported., Conclusions: Shivering is a chronic, often gradually progressive movement disorder that usually begins before 7 years of age and has a higher prevalence in tall male horses., (© 2014 EVJ Ltd.)

Reasons for Performing Study: The sensitivity and specificity of lateral cervical radiographs to evaluate horses suspected of cervical stenotic myelopathy (CSM) are limited by the assessment being restricted to the sagittal plane., Objective: To determine whether magnetic resonance imaging (MRI) allows for a more accurate identification of stenosis than lateral cervical radiographs in horses with CSM., Study Design: Case control study., Methods: Nineteen Thoroughbred horses with CSM (17 males, 2 females, age 6-50 months) were compared to 9 control Thoroughbreds (6 males, 3 females, age 9-67 months). Ante mortem, the subjects had neurological examinations and standing cervical radiographs with sagittal ratios calculated from C3 to C7. Intact cervical column MRI scans and histological examinations of the spinal cord were performed post mortem. Morphometric parameters were measured on the vertebral canal, spinal cord and intervertebral foramen., Results: Radiographic cervical canal height measurements categorised by standard minimal sagittal diameter intravertebral and intervertebral ratios produced several false positive and false negative determinations of canal stenosis as defined by spinal cord histopathology. Post mortem MRI measurements of canal area and cord canal area ratio more accurately predicted sites of cord compression in CSM cases. No differences in spinal cord measurements were observed when comparing CSM to control horses, but each of the vertebral canal parameters achieved significance at multiple sites., Conclusions: Vertebral canal area and cord canal area ratio are better parameters to predict the location of cervical canal stenosis compared to only the sagittal plane of canal height. Additional visual planes and measurements obtained by MRI, specifically vertebral canal area and the cord canal area ratio, will provide a more accurate method to identify regions of canal stenosis than lateral cervical radiographs. The development of MRI or computed tomography equipment capable of evaluating the cervical column of mature horses may substantially enhance evaluation of CSM patients. The Summary is available in Chinese - see Supporting information., (© 2013 EVJ Ltd.)

Background: Sagittal ratio values (SRVs) of cervical vertebrae are used for ante-mortem diagnosis of cervical vertebral stenotic myelopathy, but intraobserver and interobserver variability in measurement may influence radiographic interpretation of vertebral stenosis in horses with neurological disease., Objectives: To determine intraobserver repeatability in SRVs, intra- and interobserver agreement in SRVs and whether or not agreement was influenced by animal age., Animals: Forty-two horses (>1 year old) with neurological disease from which laterolateral computed radiographic images of C2-C7 were obtained., Methods: Four observers made measurements from C2 to C7 for each horse and interobserver agreement for intra- and intervertebral SRVs was determined using Bland-Altman analysis (acceptable agreement: limits of agreement [LOA] ≤ 0.05) on all horses and those ≤3 (n = 25) and >3 (n = 17) years old. Each observer also made repeated measurements for 10 horses and intraobserver repeatability and agreement were determined., Results: Adequate intraobserver repeatability was achieved for 6 sites. Within observers, paired measurements had a median difference ≤5.7%, but a large range in differences often occurred, most frequently at intervertebral sites. For C5, C6, C7, and C3-4, LOA ≤ 0.05 were achieved by at least 1 observer. With the exception of C5 for 1 pair, LOA were >0.05 for interobserver agreement, regardless of animal age. LOA were largest at intervertebral sites., Conclusions and Clinical Importance: Within and between observers, measurement error may limit the diagnostic accuracy of SRVs and result in discrepancies of diagnosis and treatment and warrants consideration when used clinically in horses with neurological disease., (Copyright © 2014 by the American College of Veterinary Internal Medicine.)

Reasons for Performing the Study: Although many studies have been performed to classify seizures by type in man and small animals, a similar study in horses is lacking., Objectives: The aims of this study were as follows: 1) to characterise the distribution of seizure types in 104 horses presented for seizure disorders to a referral veterinary hospital; and 2) to characterise the various types of seizures by identifying associated clinical factors., Study Design: Retrospective analysis of clinical records., Methods: Seizures were classified based on seizure type, according to the most recent accepted definitions in both human and small animal epileptology. History, clinical and neurological examinations, diagnostic investigations and post mortem examinations, when available, were recorded for univariable and multivariable logistic regression analyses., Results: Seizures were categorised as primary generalised in 23% of horses, focal without secondary generalisation in 42% of cases and secondary generalised in 24% of cases. The type of seizure could not be classified in 11% of cases. Significant associations were found between seizure type and the following characteristics: 1) gender; 2) frequency of seizures; and 3) presence of seizures during hospitalisation. Seizure type was not significantly associated with aetiology. For a horse with recurrent seizures, the odds of having focal seizures was 3.7 times higher (P = 0.02) than in a similar horse with nonrecurring seizures in the final logistic regression model., Conclusions: The majority of the seizures described were focal seizures with or without secondary generalisation. The clinical presentation was independent of the underlying disease., (© 2013 EVJ Ltd.)

The primary objective of this study was to investigate whether rider experience influences the assessment and grading of lameness in horses based on under-saddle gait analysis. Thirteen adult sports horses in active training were included in the study. After a baseline lameness and neurologic examination by the principal investigators, horses were videotaped while being ridden by an experienced and a less experienced rider. A 3-minute video was made for each horse and rider and 26 videos were randomly ordered and compiled on a DVD. Veterinarians with different levels of experience in evaluating lameness and veterinary students viewed the DVD and assigned a lameness score to each horse/rider combination. In a model accounting for the expertise of the evaluator, there was no difference in overall lameness scores between experienced and less experienced riders. This result was consistent for both sound and unsound horses. The overall lameness scores reported by specialists and students, however, differed significantly. The lameness score reported by the study participants while the horse was ridden was significantly associated with the subjective baseline lameness assessment reported by the principal investigators for the same limb when the horse was not under saddle. Additional work is necessary to determine whether riders with even lower skill levels would further alter the balance and motion pattern of the horse and have more influence on subjective grading of lameness.

Background: Recent work demonstrated the value of antigen-specific antibody indices (AI and C-value) to detect intrathecal antibody production against Sarcocystis neurona for antemortem diagnosis of equine protozoal myeloencephalitis (EPM)., Objectives: The study was conducted to assess whether the antigen-specific antibody indices can be reduced to a simple serum : cerebrospinal fluid (CSF) titer ratio to achieve accurate EPM diagnosis., Animals: Paired serum and CSF samples from 128 horses diagnosed by postmortem examination. The sample set included 44 EPM cases, 35 cervical-vertebral malformation (CVM) cases, 39 neurologic cases other than EPM or CVM, and 10 non-neurologic cases., Methods: Antibodies against S. neurona were measured in serum and CSF pairs using the SnSAG2 and SnSAG4/3 (SnSAG2, 4/3) ELISAs, and the ratio of each respective serum titer to CSF titer was determined. Likelihood ratios and diagnostic sensitivity and specificity were calculated based on serum titers, CSF titers, and serum : CSF titer ratios., Results: Excellent diagnostic sensitivity and specificity was obtained from the SnSAG2, 4/3 serum : CSF titer ratio. Sensitivity and specificity of 93.2 and 81.1%, respectively, were achieved using a ratio cutoff of ≤100, whereas sensitivity and specificity were 86.4 and 95.9%, respectively, if a more rigorous cutoff of ≤50 was used. Antibody titers in CSF also provided good diagnostic accuracy. Serum antibody titers alone yielded much lower sensitivity and specificity., Conclusions and Clinical Importance: The study confirms the value of detecting intrathecal antibody production for antemortem diagnosis of EPM, and they further show that the antigen-specific antibody indices can be reduced in practice to a simple serum : CSF titer ratio., (Copyright © 2013 by the American College of Veterinary Internal Medicine.)

Background: The renin-angiotensin-aldosterone system (RAAS) and hypothalamic-pituitary-adrenal axis (HPAA) and their interactions during illness and hypoperfusion are important to maintain organ function. HPAA dysfunction and relative adrenal insufficiency (RAI) are common in septic foals. Information is lacking on the RAAS and mineralocorticoid response in the context of RAI in newborn sick foals., Objectives/hypothesis: To investigate the RAAS, as well as HPAA factors that interact with the RAAS, in hospitalized foals, and to determine their association with clinical findings. We hypothesized that critical illness in newborn foals results in RAAS activation, and that inappropriately low aldosterone concentrations are part of the RAI syndrome of critically ill foals., Animals: A total of 167 foals ≤3 days of age: 133 hospitalized (74 septic, 59 sick nonseptic) and 34 healthy foals., Methods: Prospective, multicenter, cross-sectional study. Blood samples were collected on admission. Plasma renin activity (PRA) and angiotensin-II (ANG-II), aldosterone, ACTH, and cortisol concentrations were measured in all foals., Results: ANG-II, aldosterone, ACTH, and cortisol concentrations as well as ACTH/aldosterone and ACTH/cortisol ratios were higher in septic foals compared with healthy foals (P < .05). No difference in PRA between groups was found. High serum potassium and low serum chloride concentrations were associated with hyperaldosteronemia in septic foals., Conclusions and Clinical Importance: RAAS activation in critically ill foals is characterized by increased ANG-II and aldosterone concentrations. Inappropriately low cortisol and aldosterone concentrations defined as high ACTH/cortisol and ACTH/aldosterone ratios in septic foals suggest that RAI is not restricted to the zona fasciculata in critically ill newborn foals., (Copyright © 2013 by the American College of Veterinary Internal Medicine.)

Reasons for Performing Study: Although antimicrobial-associated diarrhoea (AAD) is the most frequently observed adverse effect of antimicrobial therapy in horses, few multicentred studies on the prevalence of AAD have been performed., Objectives: To determine the prevalence of AAD in horses that developed diarrhoea after antimicrobial treatment for nondiarrhoeic conditions and identify the antimicrobials used., Methods: The 2009 database of 3 referral hospitals was searched to identify nonhospitalised horses (weanling age or older) treated with antimicrobials for nongastrointestinal conditions. Horses with these criteria that presented with diarrhoea during 2009 were included in the study. Additional information, including antimicrobial administered and results of faecal pathogen testing, was gathered on each hospitalised case., Results: Of the 5251 horses treated with antimicrobials for nongastrointestinal signs, 32 were diagnosed with probable AAD, a prevalence of 0.6% (95% confidence interval: 0.43-0.86%). The AAD-diagnosed horses had an 18.8% (6/32) mortality rate. Horses with AAD had been treated for an average of 4.2 days. The most frequently used antimicrobials in horses with AAD were gentamicin in combination with penicillin (n = 7), enrofloxacin (n = 7) and doxycycline (n = 4). Clostridium difficile was identified in faecal samples from 4 horses, 2 of which died and Salmonella from 3 horses., Conclusions: Results indicated that the prevalence of AAD is low. Any antimicrobial class commonly used in equine practice is a potential cause of equine AAD. Other risk factors, such as opportunistic enteropathogens, may play a part in the development of diarrhoea secondary to antimicrobial usage., Potential Relevance: Although the risk of equine AAD is low, this sequela of antimicrobial treatment is possible especially when opportunistic enteropathogens or other risk factors are present. Because drugs from any antimicrobial class can be potentially involved in AAD, clinicians have additional incentive to ensure the judicious use of antimicrobial agents., (© 2012 EVJ Ltd.)

Tendon injuries affect all levels of athletic horses and represent a significant loss to the equine industry. Accumulation of microdamage within the tendon architecture leads to formation of core lesions. Traditional approaches to tendon repair are based on an initial period of rest to limit the inflammatory process followed by a controlled reloading program designed to promote the maturation and linear arrangement of scar tissue within the lesion. However, these treatment protocols are inefficient, resulting in prolonged recovery periods and frequent recurrence. Current alternative therapies include the use of bone marrow-derived mesenchymal stem cells (BMSC) and a population of nucleated cells from adipose containing adipose-derived mesenchymal stem cells (AdMSC). Umbilical cord blood-derived stem cells (UCB) have recently received attention for their increased plasticity in vitro and potential as a therapeutic aid. Both BMSC and AdMSC require expansion in culture before implantation to obtain a pure stem cell population, limiting the time frame for implantation. Collected at parturition, UCB can be cryopreserved for future use. Furthermore, the low immunogenicity of the UCB population allows for allogeneic implantation. Current research indicates that BMSC, AdMSC, and UCB can differentiate into tenocyte-like cells in vitro, increasing expression of scleraxis, tenascin c, and extracellular matrix proteins. When implanted, BMSC and AdMSC engraft into the tendon and improve tendon architecture. However, treatment with these stem cells does not decrease recovery period. Furthermore, the resulting regeneration is not optimal, as the resulting tissue is still inferior to native tendon. Umbilical cord blood-derived stem cells may provide an alternate source of stem cells that promote improved regeneration of tendon tissue. A more naïve cell population, these cells may have a greater rate of engraftment as well as an increased ability to secrete bioactive factors and recruit additional reparative cells. Further work should clarify the role of distinct stem cell sources in the regenerating tendon and the need for a naïve or differentiated cell type for implantation.

Reasons for Performing Study: Fibrotic myopathy can cause incapacitating gait abnormalities. Transection of the fibrotic mass followed by early post operative exercise is the best treatment for fibrotic myopathy. A laser may be used to transect the fibrotic mass. Assessment of the effectiveness of therapies for fibrotic myopathy has been limited to subjective evaluation., Objectives: To objectively assess gait abnormalities associated with fibrotic myopathy before and after laser fibrotomy followed by early post operative exercise., Methods: Kinematic evaluation of horses with fibrotic myopathy walking and trotting on a treadmill was used to investigate hindfeet trajectories (n = 8) and lameness (n = 5) before and after laser fibrotomy Hoof flight trajectory length (HFTL), relative protraction length (% PL), maximum hoof height during swing (MXHH), hoof height at end of protraction (HH(pro)) and retraction (HH(ret)) were measured and differences between fibrotic myopathy affected and nonaffected limbs were calculated. Lameness was quantified by measuring maximum and minimum pelvic height differences between right and left halves of the stride., Results: Before surgery the foot of the fibrotic myopathy affected limb had abnormal trajectories characterised as increased HFTL, MXHH and HH(pro) and decreased % PL and HH(ret) and the 5 horses objectively evaluated for lameness were lame in the fibrotic myopathy affected limb. Immediately after surgery the difference between affected and nonaffected limbs decreased for HFTL, % PL and HH(pro). Six to 11 weeks after surgery, the HFTL difference increased but was still smaller than before surgery, which was interpreted as partial recurrence of the gait abnormality; all horses objectively evaluated for lameness were either improved (n = 1) or not lame (n = 4) in the previously affected, operated limb., Conclusions: Fibrotic myopathy affects the foot flight and leads to asymmetric vertical excursion of the pelvis. Laser fibrotomy followed by early post operative exercise can minimise these abnormalities., Potential Relevance: Laser fibrotomy combined with early post operative exercise is a viable therapy for fibrotic myopathy.

Reasons for Performing the Study: In contrast with reports in man and small animals, a systematic classification of seizures in horses is lacking., Objectives: The purpose of this study was to classify seizures based on their aetiology and to characterise epilepsy in 104 horses presented for seizures at the Ohio State University Veterinary Medical Center between 1988 and 2009., Methods: In a retrospective observational study, seizures were classified by aetiology based on history, clinical observations, diagnostic investigations (e.g. electroencephalograms, cerebrospinal fluid and computed tomography imaging of the head) and post mortem examinations, when available. Univariate and multivariate logistic regression analyses were performed., Results: Epilepsy (i.e. 2 or more recurrent seizures) was identified in 70% of cases, and further classified as symptomatic (i.e. structural brain pathology, 35.6% of cases), cryptogenic (i.e. unknown, 54.8% of cases) and idiopathic (i.e. suspected genetic predisposition, 2.7% of cases). Normal neurological examination on admission, the presence of seizures unprovoked by any identified factors and paroxysmal epileptiform activity on electroencephalogram recordings were all strongly (P<0.05) correlated with epilepsy on univariate analysis. For a horse with generalised seizures, the odds of having epilepsy was 7 times lower compared with a similar horse with partial seizures (P<0.05) in multivariate modelling., Conclusions: Seizure aetiology was symptomatic or cryptogenic in most horses, whereas reactive seizures and idiopathic epilepsy were less common., Potential Relevance: This study is the first attempt to classify seizures and to characterise epilepsy in a referral-based equine population. Predictive factors of epilepsy in horses were similar to those reported in other species and may assist the clinician with the early diagnosis of epilepsy., (© 2011 EVJ Ltd.)

Reasons for Performing Study: Subjective evaluation of mild lameness has been shown to have poor interobserver reliability. Traditional methods of objective lameness evaluation require specialised conditions and equipment. Wireless inertial sensor systems have been developed to allow for simple, rapid, objective lameness detection in horses trotted over ground., Objective: The purpose of this study was to compare the sensitivities of an inertial sensor system and subjective evaluation performed by experienced equine practitioners at detecting lameness in horses. We hypothesised that the inertial sensor system would identify lameness at a lower level of sole pressure than a consensus of 3 experienced equine veterinarians., Methods: Fifteen horses were fitted with special shoes that allowed for lameness induction via sole pressure. Horses were simultaneously evaluated by 3 equine veterinarians and a wireless inertial sensor system. Horses were subjected to multiple trials: 1) before inserting the screw; 2) after inserting the screw to just touch the sole; and 3) after tightening the screw in half turn increments. The number of screw turns required for lameness identification in the correct limb by the inertial sensors and by consensus of 3 equine veterinarians was compared using the Wilcoxon test., Results: The inertial sensor system selected the limb with the induced lameness after fewer screw turns than did the 3 veterinarians (P<0.0001). The inertial sensor system selected the correct limb before the 3 veterinarians in 35 trials (58.33%), the evaluators selected the correct limb before the inertial sensors in 5 trials (8.33%), and in 20 trials (33.33%) they selected the correct limb at the same time., Potential Relevance: The inertial sensor system was able to identify lameness at a lower level of sole pressure than the consensus of 3 equine veterinarians. The inertial sensor system may be an effective aid to lameness localisation in clinical cases., (© 2012 EVJ Ltd.)

Background: Pituitary pars intermedia dysfunction (PPID) is common in older horses., Objectives: To determine diagnosis frequency, prognostic factors, long-term survival, and owner satisfaction with treatment., Animals: Medical records from horses diagnosed with PPID, 1993-2004., Methods: A retrospective cohort design with data collected from the Veterinary Medical Data Base (VMDB) and a cohort of 3 VTHs. Proportional accessions, annual incidence, and demographics were compared for all accessions. During the same period, a subset of medical records (n = 44) was extracted and owners (n = 34) contacted to obtain long-term follow-up information., Results: Diagnoses of PPID were reported for 217 horses that presented to VTHs and were reported to the VMDB. Proportional diagnosis increased from 0.25/1,000 in 1993 to 3.72/1,000 in 2002. For 44 horses included in the follow-up study, the most commons signs were hirsutism (84%) and laminitis (50%). Of 34 horse owners contacted, the average time from onset of signs to diagnosis was 180 days. Improvement in ≥ 1 signs, 2 months after diagnosis, was reported by 9/22 (41%) of horse owners. Clinical signs and clinicopathologic data were not associated with survival, and 50% of horses were alive 4.6 years after diagnosis. Cause of death among horses (15/20; 85%) was euthanasia, and 11/15 (73%) were euthanized because of conditions associated with PPID. Most horse owners (28/29; 97%) said they would treat a second horse for PPID., Conclusion and Clinical Importance: PPID was diagnosed with increasing frequency, and 50% of horses survived 4.5 years after diagnosis. Owners were satisfied with their horses' quality of life and would treat a second horse if diagnosed., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)

Reasons for Performing Study: No large scale epidemiological studies have previously quantified the occurrence of carpal, metacarpo- and metatarsophalangeal (MCP/MTP) joint injuries in Thoroughbred racehorses., Objectives: To develop an objective classification system for carpal and MCP/MTP joint injuries and estimate the incidence of these injuries in young Thoroughbreds in flat race training., Methods: In a prospective cohort study, data on daily exercise and veterinary-diagnosed carpal and MCP/MTP joint injuries were collected from Thoroughbreds monitored since starting training as yearlings, for up to 2 years. Cases were classified in one of 4 categories: 1) localised to a carpal or MCP/MTP joint based on clinical examination and/or diagnostic analgesia; no diagnostic imaging performed; 2) localised to a carpal or MCP/MTP joint based on clinical examination and/or diagnostic analgesia; radiographs taken but no abnormalities detected; 3) evidence of abnormality of subchondral bone and/or articular margin(s) on diagnostic imaging and 4) evidence of discontinuity of the articular surface on diagnostic imaging. Incidence rates and rate ratios were estimated using Poisson regression, adjusting for trainer-level clustering., Results: A total of 647 horses from 13 trainers throughout England contributed 7785 months at risk of joint injury. One-hundred-and-eighty-four cases of carpal (n = 82) or MCP/MTP (n = 102) joint injury were reported in 165 horses and classified in Category 1 (n = 21), Category 2 (n = 21), Category 3 (n = 72) or Category 4 (n = 70). The overall joint injury rate was 1.8 per 100 horse months (95% CI = 1.2, 2.8); rates did not differ significantly between 2- and 3-year-olds but females sustained Category 1 injuries at triple the rate of males (P = 0.03). Joint injury rates differed significantly between trainers (P<0.001) and there was trainer variation in anatomical site and severity of injury., Conclusions and Potential Relevance: Carpal and MCP/MTP joint injuries are an important cause of morbidity in Thoroughbred racehorses. Identification of modifiable risk factors for these injuries may reduce their incidence., (© 2011 EVJ Ltd.)

Background: Diagnosis of equine protozoal myeloencephalitis (EPM) remains a challenge for equine practitioners. Current utilized methods have inadequate sensitivity and specificity, because of a high number of false positive results., Hypothesis/objective: Evaluation of antibody indices to Sarcocystis neurona should provide high sensitivity and specificity for diagnosis of EPM., Animals: Archived samples from 29 clinical patients., Methods: Archived serum and cerebrospinal fluid (CSF) samples from clinical patients with either EPM (14) or cervical vertebral compressive myelopathy (CVM) (15) were examined and tested for anti-S. neurona antibodies by the SnSAG2 ELISA. The results were used to calculate the antibody index (AI) and C-value. Sensitivity and specificity were calculated, and the AI, C-value, immunoglobulin G (IgG) concentrations, and anti-S. neurona titers compared. In addition, negative CSF was spiked in varying concentrations with blood from a horse with a high anti-S. neurona titer, and the tests repeated., Results: Results demonstrated that the IgG concentration, anti-S. neurona titer, AI, and C-value were significantly higher (P < .05) in horses with EPM than in those with CVM. Sensitivity and specificity of the AI was 71 and 100%, respectively, and that of the C-value was 86 and 100%, respectively. In addition, the AI and C-value from the samples spiked with S. neurona positive blood remained below 1 (eg, negative) in CSF with a red blood cell (RBC) count up to 10(5) RBC/μL. CONCLUSIONS/CLINICAL IMPORTANCE: Results of the study demonstrate the value of calculating the AI and C-value in the diagnosis of EPM in horses. In addition, the test is robust in the presence of blood contamination., (Copyright © 2010 by the American College of Veterinary Internal Medicine.)

Objective: To compare signalment of horses with cervical vertebral malformation-malarticulation (CVM) with that of control horses and to describe results of clinical examination, diagnostic imaging and necropsy findings, and reported outcome in horses with CVM., Design: Retrospective case-control study., Animals: 270 horses with CVM and 608 control horses admitted to 6 veterinary hospitals from 1992 through 2007., Procedures: Medical records of participating hospitals were reviewed to identify horses with CVM (ie, case horses) and contemporaneous control (non-CVM-affected) horses that were admitted for treatment. Signalment was compared between case horses and control horses. Results of clinical examination, laboratory and diagnostic imaging findings, necropsy results, and outcome were assessed for horses with CVM., Results: Case horses were younger (median age, 2 years) than were control horses (median age, 7 years). Thoroughbreds, warmbloods, and Tennessee Walking Horses were overrepresented in the CVM group. Gait asymmetry and cervical hyperesthesia were frequently detected in horses with CVM. Vertebral canal stenosis and articular process osteophytosis were commonly observed at necropsy; agreement between the results of radiographic or myelographic analysis and detection of lesions at necropsy was 65% to 71% and 67% to 78%, respectively. Of 263 horses with CVM for which outcome was recorded, 1 died and 172 (65.4%) were euthanatized., Conclusions and Clinical Relevance: Odds of a diagnosis of CVM were greater in young horses and horses of specific breeds. Detection of gait asymmetry and cervical hyperesthesia were frequently reported in association with CVM. Accurate diagnosis of lesions associated with CVM by use of radiography and myelography can be challenging.

Reasons for Performing Study: The use of computer tomography (CT) and contrast-enhanced CT (CCT) to image the head is common. However, the validity of CT as a neurodiagnostic indicator of intracranial diseases in horses is unknown., Objective: To define the validity of CT and CCT in horses with suspected intracranial disorders., Methods: The validity of CT imaging was estimated by comparing clinical, clinicopathological and histopathological findings to CT findings in 15 horses presented for intracranial disorders, for which pre- and post contrast CT images and post mortem examination of the brain and skull were reviewed. Post mortem examination (gross and histopathological examination) was considered as the gold standard; and sensitivity, specificity, predictive values, likelihood ratios, and pre- and post test probabilities were calculated., Results: All horses had abnormal neurological examinations on admission. Computer tomography imaging identified intracranial lesions in 8 horses, and included masses (oligodendroglioma, adenocarcinoma and cholesterinic granulomas), acute haemorrhage and skull fractures. Computer tomography imaging failed to identify intracranial lesions in 6 cases, which included meningitis, meningoencephalitis and nonacute haemorrhage. Lesions not recognised by CT were also not evident on gross examination but were identified by histopathological examination of the brain. Post mortem examination of the brain and skull was unremarkable in one horse, for which cranial CT imaging was normal (specificity, 100%). Therefore, the odds of having an intracranial lesion after an abnormal CT were very high. In contrast, there was a moderate sensitivity (57.1%, 95% confidence interval: 29.6-81.2)., Conclusions and Potential Relevance: CT was an excellent neurodiagnostic tool in identifying skull fractures, intracranial space-occupying lesions (e.g. neoplasia) and acute haemorrhage and allows to rule in intracranial disorders. However, CT showed limited sensitivity in identifying inflammatory disorders and small parenchymal lesions in the equine brain, which was not further detectable after contrast administration.

Sarcocystis neurona is the most important cause of equine protozoal myeloencephalitis (EPM), a neurologic disease of the horse. In the present work, the kinetics of S. neurona invasion is determined in the equine model. Six ponies were orally inoculated with 250 x 10(6) S. neurona sporocysts via nasogastric intubation and killed on days 1, 2, 3, 5, 7, and 9 postinoculation (PI). At necropsy, tissue samples were examined for S. neurona infection. The parasite was isolated from the mesenteric lymph nodes at 1, 2, and 7 days PI; the liver at 2, 5, and 7 days PI; and the lungs at 5, 7, and 9 days PI by bioassays in interferon gamma gene knock out mice (KO) and from cell culture. Microscopic lesions consistent with an EPM infection were observed in brain and spinal cord of ponies killed 7 and 9 days PI. Results suggest that S. neurona disseminates quickly in tissue of naive ponies.

The ability of ponazuril to prevent or limit clinical signs of equine protozoal myeloencephalitis (EPM) after infection with Sarcocystis neurona was evaluated. Eighteen horses were assigned to 1 of 3 groups: no treatment, 2.5 mg/kg ponazuril, or 5.0 mg/kg ponazuril. Horses were administered ponazuril, once per day, beginning 7 days before infection (study day 0) and continuing for 28 days postinfection. On day 0, horses were stressed by transport and challenged with 1 million S. neurona sporocysts per horse. Sequential neurologic examinations were performed, and serum and cerebrospinal fluid were collected and assayed for antibodies to S. neurona. All horses in the control group developed neurologic signs, whereas only 71 and 40% of horses in the 2.5 and 5.0 mg/kg ponazuril groups, respectively, developed neurologic abnormalities. This was significant at P = 0.034 by using Fisher exact test. In addition, seroconversion was decreased in the 5.0 mg/kg group compared with the control horses (100 vs. 40%; P = 0.028). Horses with neurologic signs were killed, and a post-mortem examination was performed. Mild-to-moderate, multifocal signs of neuroinflammation were observed. These results confirm that treatment with ponazuril at 5.0 mg/kg minimizes, but does not eliminate, infection and clinical signs of EPM in horses.

Amongst the infectious diseases that threaten equine health, herpesviral infections remain a world wide cause of serious morbidity and mortality. Equine herpesvirus-1 infection is the most important pathogen, causing an array of disorders including epidemic respiratory disease abortion, neonatal foal death, myeloencephalopathy and chorioretinopathy. Despite intense scientific investigation, extensive use of vaccination, and established codes of practice for control of disease outbreaks, infection and disease remain common. While equine herpesvirus-1 infection remains a daunting challenge for immunoprophylaxis, many critical advances in equine immunology have resulted in studies of this virus, particularly related to MHC-restricted cytotoxicity in the horse. A workshop was convened in San Gimignano, Tuscany, Italy in June 2004, to bring together clinical and basic researchers in the field of equine herpesvirus-1 study to discuss the latest advances and future prospects for improving our understanding of these diseases, and equine immunity to herpesviral infection. This report highlights the new information that was the focus of this workshop, and is intended to summarize this material and identify the critical questions in the field.

Equine protozoal myeloencephalitis (EPM) is a serious neurologic disease of horses caused primarily by the protozoal parasite Sarcocystis neurona. Currently available antemortem diagnostic testing has low specificity. The hypothesis of this study was that serum and cerebrospinal fluid (CSF) of horses experimentally challenged with S neurona would have an increased S neurona-specific IgM (Sn-IgM) concentration after infection, as determined by an IgM capture enzyme linked immunoassay (ELISA). The ELISA was based on the S neurona low molecular weight protein SNUCD-1 antigen and the monoclonal antibody 2G5 labeled with horseradish peroxidase. The test was evaluated using serum and CSF from 12 horses experimentally infected with 1.5 million S neurona sporocysts and 16 horses experimentally infected with varying doses (100 to 100,000) of S neurona sporocysts, for which results of histopathologic examination of the central nervous system were available. For horses challenged with 1.5 million sporocysts, there was a significant increase in serum Sn-IgM concentrations compared with values before infection at weeks 2-6 after inoculation (P < .0001). For horses inoculated with lower doses of S neurona, there were significant increases in serum Sn-IgM concentration at various points in time after inoculation, depending on the challenge dose (P < .01). In addition, there was a significant increase between the CSF Sn-IgM concentrations before and after inoculation (P < .0001). These results support further evaluation of the assay as a diagnostic test during the acute phase of EPM.

Previous challenge studies performed at Ohio State University involved a transport-stress model where the study animals were dosed with Sarcocystis neurona sporocysts on the day of arrival. This study was to test a second transportation of horses after oral inoculation with S. neurona sporocysts. Horses were assigned randomly to groups: group 1, transported 4 days after inoculation (DAI); group 2, at 11 DAI; group 3, at 18 DAI; and group 4, horses were not transported a second time (controls). An overall neurologic score was determined on the basis of a standard numbering system used by veterinarians. All scores are out of 5, which is the most severely affected animal. The mean score for the group 1 horses was 2.42; group 2 horses was 2.5; group 3 horses was 2.75; and group 4 horses was 3.25. Because the group 4 horses did not have a second transport, they were compared with all other groups. Statistically different scores were present between group 4 and groups 1 and 2. There was no difference in the time of seroconversion between groups. There was a difference between the time of onset of first clinical signs between groups 1 and 4. This difference was likely because of the different examination days. Differences in housing and handling were likely the reason for the differences in severity of clinical signs. This model results in consistent, significant clinical signs in all horses at approximately the same time period after inoculation but was most severe in horses that did not experience a second transport.

Sarcocystis neurona and Sarcocystis fayeri infections are common in horses in the Americas. Their antemortem diagnosis is important because the former causes a neurological disorder in horses, whereas the latter is considered nonpathogenic. There is a concern that equine antibodies to S. fayeri might react with S. neurona antigens in diagnostic tests. In this study, 4 ponies without demonstrable serum antibodies to S. neurona by Western immunoblot were used. Three ponies were fed 1 x 10(5) to 1 x 10(7) sporocysts of S. fayeri obtained from dogs that were fed naturally infected horse muscles. All ponies remained asymptomatic until the termination of the experiment, day 79 postinoculation (PI). All serum samples collected were negative for antibodies to S. neurona using the Western blot at the initial screening, just before inoculation with S. fayeri (day 2) and weekly until day 79 PI. Cerebrospinal fluid samples from each pony were negative for S. neurona antibodies. Using the S. neurona agglutination test, antibodies to S. neurona were not detected in 1:25 dilution of sera from any samples, except that from pony no. 4 on day 28; this pony had received 1 X 10(7) sporocysts. Using indirect immunofluorescence antibody tests (IFATs), 7 serum samples were found to be positive for S. neurona antibodies from 1:25 to 1:400 dilutions. Sarcocystis fayeri sarcocysts were found in striated muscles of all inoculated ponies, with heaviest infections in the tongue. All sarcocysts examined histologically appeared to contain only microcytes. Ultrastructurally, S. fayeri sarcocysts could be differentiated from S. neurona sarcocysts by the microtubules (mt) in villar protrusions on sarcocyst walls; in S. fayeri the mt extended from the villar tips to the pellicle of zoites, whereas in S. neurona the mt were restricted to the middle of the cyst wall. Results indicate that horses with S. fayeri infections may be misdiagnosed as being S. neurona infected using IFAT, and further research is needed on the serologic diagnosis of S. neurona infections.

Equine protozoal myeloencephalitis (EPM) is a serious neurologic disease in the horse most commonly caused by Sarcocystis neurona. The domestic cat (Felis domesticus) is an intermediate host for S. neurona. In the present study, nine farms, known to have prior clinically diagnosed cases of EPM and a resident cat population were identified and sampled accordingly. In addition to the farm cats sampled, samples were also collected from a mobile spay and neuter clinic. Overall, serum samples were collected in 2001 from 310 cats, with samples including barn, feral and inside/outside cats. Of these 310 samples, 35 were from nine horse farms. Horse serum samples were also collected and traps were set for opossums at each of the farms. The S. neurona direct agglutination test (SAT) was used for both the horse and cat serum samples (1:25 dilution). Fourteen of 35 (40%) cats sampled from horse farms had circulating S. neurona agglutinating antibodies. Twenty-seven of the 275 (10%) cats from the spay/neuter clinic also had detectable S. neurona antibodies. Overall, 115 of 123 (93%) horses tested positive for anti-S. neurona antibodies, with each farm having greater than a 75% exposure rate among sampled horses. Twenty-one opossums were trapped on seven of the nine farms. Eleven opossums had Sarcocystis sp. sporocysts, six of them were identified as S. neurona sporocysts based on bioassays in gamma-interferon gene knockout mice with each opossum representing a different farm. Demonstration of S. neurona agglutinating antibodies in domestic and feral cats corroborates previous research demonstrating feral cats to be naturally infected, and also suggests that cats can be frequently infected with S. neurona and serve as one of several natural intermediate hosts for S. neurona.

The effect of inoculation dose of Sarcocystis neurona sporocysts on the development of clinical neurologic disease in horses was investigated. Twenty-four seronegative weanling horses were subjected to the natural stress of transport and then randomly assigned to 6 treatment groups of 4 horses each. Horses were then immediately inoculated with either 10(2), 10(3), 10(4), 10(5), or 10(6) S. neurona sporocysts or placebo using nasogastric tube and housed indoors. Weekly neurologic examinations were performed by a blinded observer. Blood was collected weekly for antibody determination by Western blot analysis. Cerebrospinal fluid was collected before inoculation and before euthanasia for S. neurona antibody determination. Horses were killed and necropsied between 4 and 5 wk after inoculation. Differences were detected among dose groups based on seroconversion times, severity of clinical neurologic signs, and presence of microscopic lesions. Seroconversion of challenged horses was observed as early as 14 days postinfection in the 10(6) sporocyst dose group. Mild to moderate clinical signs of neurologic disease were produced in challenged horses from all groups, with the most consistent signs seen in the 10(6) sporocyst dose group. Histologic lesions suggestive of S. neurona infection were detected in 4 of the 20 horses fed sporocysts. Parasites were not detected in equine tissues by light microscopy, immunohistochemistry, or bioassay in gamma-interferon gene knockout mice. Control horses remained seronegative for the duration of the study and had no histologic evidence of protozoal infection.

Twelve foals, age 3-9 months, examined at The Ohio State University Veterinary Teaching Hospital between 1995 and 2000 were diagnosed with chronic pulmonary disease associated with marked interstitial opacity on radiographic examination. The most characteristic features were a history of respiratory disease of 1-3 months duration, marked clinical signs of respiratory disease, failure to yield a consistent pathogen from tracheobronchial aspirates and a predominantly interstitial pattern on thoracic radiographs. We attributed these signs to chronic interstitial pneumonia. Foals were treated with broad spectrum antimicrobial and corticosteroid drugs. All 12 foals were discharged alive from hospital and, of the 10 available for follow-up, all were disease-free and performing to expectation 5 months to 5 years after discharge. We conclude that chronic interstitial pneumonia, occuring in foals, is associated with a good prognosis and that corticosteroid therapy may be useful in its treatment.

Upon ingestion of adult aquatic insects, horses developed clinical signs of Potomac horse fever, and Neorickettsia risticii was isolated from the blood. 16S rRNA and 51-kDa antigen gene sequences from blood, isolates, and caddis flies fed to the horses were identical, proving oral transmission of N. risticii from caddis flies to horses.

Suppurative lower airway disease is a common debilitating disease in performance horses and, while rarely fatal, is often recalcitrant to conventional therapy. A variety of treatments have been used to combat this condition and we conducted two types of studies to determine if caprine serum fraction--immunomodulator (CSFI), a nonspecific immunomodulator, improved recovery from lower respiratory disease. Two dose response studies were performed to ascertain the efficacy of CSFI. Horses were maintained daily on conventional antibiotic therapy. Respiratory tract exudate, nasal discharge, dyspnoea, chest auscultation and cough frequency were monitored weekly. One hundred percent of the horses treated with 2 i.m. injections of either 60 or 120 mg CSFI one week apart showed significant improvement with each weekly evaluation and were fully recovered by week 3. Horses treated with 15 or 30 mg CSFI did not differ significantly from the control group. Only 10% of the control horses responded to conventional antibiotic therapy. An expanded field trial utilising 80 horses diagnosed with lower respiratory disease and housed at 4 equine clinics was conducted. Thirty-five percent of the 40 control horses, treated solely by conventional antibiotic therapies, recovered while 75% of the horses treated with a supplemental administration of 60 mg CSFI as described above recovered. The combined data from these studies showed that CSFI was able to promote an overall recovery from lower respiratory disease of 86%.

Electroencephalography (EEG) is a valuable diagnostic test to identify functional disturbances in brain activity. The purpose of this study was to assess the validity of EEG as a diagnostic indicator of intracranial diseases in horses. The validity of EEG was estimated by comparing clinical, clinicopathologic, and histopathologic findings to EEG findings in 20 horses examined for seizures. collapse, or abnormal behavior between 1984 and 1997. A bipolar left-to-right, back-to-front montage and a bipolar circular montage were recorded from sedated (4) and anesthetized (16) horses. Visual and semiquantitative masked analysis of EEG recording Ist was validated on 10 horses presented for problems other than intracranial diseases. EEG pattern was normal in 7 of the 20 clinically affected horses. Abnormal EEG patterns included high-voltage slow waves and discrete paroxysmal activity with or without generalized activity in 13 horses. Histopathologic diagnoses in 10 horses included meningoencephalitis, neuronal necrosis, congenital anomalies. cerebral edema. and abscess. All of these horses had abnormal EEG patterns (sensitivity, 100%) with a positive neuroanatomic correlation in 7 animals. Localization of histopathologic and EEG abnormalities did not correlate in 15% of the horses (3/20). The cause of neurologic signs could not be explained at postmortem examination in 10 animals and the EEG pattern was normal in 7 of these horses (specificity, 70%). In conclusion, equine EEG was a sensitive tool in the diagnosis of intracranial disorders.

Equine protozoal myeloencephalitis (EPM) is a neurologic disease of horses most commonly caused by the protozoan parasite Sarcocystis neurona. Until recently the only treatment option was the combination of a sulfonamide with pyrimethamine. The present study was performed to assess the efficacy of ponazuril, an anticoccidial triazine-based compound, as a treatment for naturally occurring EPM. One hundred one horses with EPM were randomly allocated to treatment with ponazuril 15% oral paste at either 5 or 10 mg/kg body weight for 28 consecutive days. Horses were evaluated clinically and by analysis of blood and cerebrospinal fluid (CSF) before and 28 and 118 days after the start of treatment. Clinical success was defined as either an improvement in neurologic score by at least one grade (on a 0 to 5 scale) or conversion to negative status on Western blot for S. neurona antibodies by 90 days following cessation of treatment. Overall, 62% of the horses, including 28 of 47 treated with ponazuril at 5 mg/kg and 35 of 54 treated with 10 mg/kg, met the criteria for successful treatment. The Western blot for CSF became negative in 10% (10/101) of the horses. Quantification of the anti-17kDa antibody response in Western blot (relative quantity CSF) did not reveal a significant change in response to treatment. However, immunoglobulin index did decrease significantly during treatment (P = .01). The findings of this study support the efficacy of ponazuril for the treatment of EPM.

Neurologic disease in horses caused by Sarcocystis neurona is difficult to diagnose, treat, or prevent, due to the lack of knowledge about the pathogenesis of the disease. This in turn is confounded by the lack of a reliable equine model of equine protozoal myeloencephalitis (EPM). Epidemiologic studies have implicated stress as a risk factor for this disease, thus, the role of transport stress was evaluated for incorporation into an equine model for EPM. Sporocysts from feral opossums were bioassayed in interferon-gamma gene knockout (KO) mice to determine minimum number of viable S. neurona sporocysts in the inoculum. A minimum of 80,000 viable S. neurona sporocysts were fed to each of the nine horses. A total of 12 S. neurona antibody negative horses were divided into four groups (1-4). Three horses (group 1) were fed sporocysts on the day of arrival at the study site, three horses were fed sporocysts 14 days after acclimatization (group 2), three horses were given sporocysts and dexamethasone 14 days after acclimatization (group 3) and three horses were controls (group 4). All horses fed sporocysts in the study developed antibodies to S. neurona in serum and cerebrospinal fluid (CSF) and developed clinical signs of neurologic disease. The most severe clinical signs were in horses in group 1 subjected to transport stress. The least severe neurologic signs were in horses treated with dexamethasone (group 3). Clinical signs improved in four horses from two treatment groups by the time of euthanasia (group 1, day 44; group 3, day 47). Post-mortem examinations, and tissues that were collected for light microscopy, immunohistochemistry, tissue cultures, and bioassay in KO mice, revealed no direct evidence of S. neurona infection. However, there were lesions compatible with S. neurona infection in horses. The results of this investigation suggest that stress can play a role in the pathogenesis of EPM. There is also evidence to suggest that horses in nature may clear the organism routinely, which may explain the relatively high number of normal horses with CSF antibodies to S. neurona compared to the prevalence of EPM.

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, ponies, and Southern sea otters. Cats can act as an experimental intermediate host harboring the sarcocyst stage after ingesting sporocysts. This paper reviews information on the history, structure, life cycle, biology, pathogenesis, induction of disease in animals, clinical signs, diagnosis, pathology, epidemiology, and treatment of EPM caused by S. neurona.

Recent advances in the understanding of the parasite life cycle, epidemiology, clinical signs, diagnosis, treatment, and prevention of EPM are reviewed. The NAHMS Equine '98 study and a controlled retrospective study from The Ohio State University College of Veterinary Medicine identified a number of risk factors associated with development of the disease. The national annual incidence of EPM was 1% or less depending on the primary use of the animals. Increased disease risk was associated with age (1-5 and > 13 years of age), season (lowest in winter months and increasing with ambient temperature), previous stressful events, the presence of opossums, the use of nonsurface water drinking systems, and failure to restrict wildlife access to feed. Horses that received treatment were 10 times more likely to improve, and those that improved were 50 times more likely to survive. A number of recent studies confirmed that horses can be experimentally infected with S. neurona; however, large numbers of sporocysts are apparently necessary to achieve infection, and clinical signs and abnormal CNS histology are only seen inconsistently. Results suggest that CNS infection and positive CSF immunoblot findings may be transient phenomena among naturally infected horses. Although immunosuppression may be involved in the development of EPM, some element of the immune response seems to be necessary for the development of clinical signs. Use of the standard immunoblot test for the detection of anti-S. neurona antibodies in CSF continues to provide the most useful adjunct to a detailed neurologic examination for the diagnosis of EPM. Test sensitivity and specificity were 89% in 295 horses euthanatized because of neurologic disease, of which 123 were confirmed cases of EPM. The PPV was 85%, and the NVP was 92%. A number of promising new EPM treatments are under investigation. In addition to standard SDZ/PYR therapy, toltrazuril, ponazuril, diclazuril, and NTZ have shown promise as possible alternatives.

Objective: To investigate risk factors for use in predicting clinical improvement and survival of horses with equine protozoal myeloencephalitis (EPM)., Design: Longitudinal epidemiologic study., Animals: 251 horses with EPM., Procedure: Between 1992 and 1995, 251 horses with EPM were admitted to our facility. A diagnosis of EPM was made on the basis of neurologic abnormalities and detection of antibody to Sarcocystis neurona or S neurona DNA in CSF. Data were obtained from hospital records and through telephone follow-up interviews. Factors associated with clinical improvement and survival were analyzed, using multivariable logistic regression., Results: The likelihood of clinical improvement after diagnosis of EPM was lower in horses used for breeding and pleasure activities. Treatment for EPM increased the probability that a horse would have clinical improvement. The likelihood of survival among horses with EPM was lower among horses with more severe clinical signs and higher among horses that improved after EPM was diagnosed., Conclusions and Clinical Relevance: Treatment of horses with EPM is indicated in most situations; however, severity of clinical signs should be taken into consideration when making treatment decisions. Response to treatment is an important indicator of survival.

Objective: To investigate risk factors for development of equine protozoal myeloencephalitis (EPM) in horses., Design: Case-control study., Animals: 251 horses admitted to The Ohio State University Veterinary Teaching Hospital from 1992 to 1995., Procedure: On the basis of clinical signs of neurologic disease and detection of antibody to Sarcocystis neurona or S neurona DNA in cerebrospinal fluid, a diagnosis of EPM was made for 251 horses. Two contemporaneous series of control horses were selected from horses admitted to the hospital. One control series (n = 225) consisted of horses with diseases of the neurologic system other than EPM (neurologic control horses), and the other consisted of 251 horses admitted for reasons other than nervous system diseases (nonneurologic control horses). Data were obtained from hospital records and telephone conversations. Risk factors associated with disease status were analyzed, using multivariable logistic regression., Results: Horses ranged from 1 day to 30 years old (mean +/- SD, 5.7 +/- 5.2 years). Risk factors associated with an increased risk of developing EPM included age, season of admission, prior diagnosis of EPM on the premises, opossums on premises, health events prior to admission, and racing or showing as a primary use. Factors associated with a reduced risk of developing EPM included protection of feed from wildlife and proximity of a creek or river to the premises where the horse resided., Conclusions and Clinical Relevance: Development of EPM was associated with a number of management-related factors that can be altered to decrease the risk for the disease.

Objective: To determine whether physical examination, laboratory, or radiographic abnormalities in foals with Rhodococcus equi infection were associated with survival, ability to race at least once after recovery, or, for foals that survived and went on to race, subsequent racing performance., Design: Retrospective study., Animals: 49 Thoroughbreds and 66 Standardbreds admitted to 1 of 6 veterinary teaching hospitals between 1984 and 1992 in which R equi infection was positively diagnosed., Procedure: Results of physical examination, laboratory testing, and thoracic radiography were reviewed. Indices of racing performance were obtained for foals that recovered and eventually raced and compared with values for the US racing population., Results: 83 (72%) foals survived. Foals that did not survive were more likely to have extreme tachycardia (heart rate > 100 beats/min), be in respiratory distress, and have severe radiographic abnormalities on thoracic radiographs at the time of initial examination than were foals that survived. Clinicopathologic abnormalities were not associated with whether foals did or did not survive. Forty-five of the 83 surviving foals (54%) eventually raced at least once, but none of the factors examined was associated with whether foals went on to race. Racing performance of foals that raced as adults was not significantly different from that of the US racing population., Clinical Implications: R equi infection in foals is associated with a decreased chance of racing as an adult; however, foals that eventually go on to race perform comparably to the US racing population.

Potomac horse fever is an acute systemic equine disease caused by Ehrlichia risticii. Currently, serologic methods are widely used to diagnose this disease. However, serologic methods cannot determine whether the horse is presently infected or has been exposed to ehrlichial antigens in the past. The purpose of the present study was to compare the sensitivities of the nested PCR and cell culture with that of the indirect fluorescent-antibody (IFA) test for the diagnosis of Potomac horse fever. Blood and fecal specimens serially collected from a pony experimentally infected with E. risticii Maryland, blood specimens serially collected from mice inoculated with E. risticii Ohio 380, and blood and/or fecal specimens collected from 27 horses which had clinical signs compatible with Potomac horse fever were examined. These horses resided in Kentucky, Indiana, Pennsylvania, and Vermont. The IFA test titer became positive after 6 days postinoculation (p.i.) for the pony. A culture of the blood of the pony was positive for E. risticii starting on day 1 and was positive through day 28 p.i. By the nested PCR, E. risticii was detectable in the blood and feces of the pony starting on day 1 and was detectable through day 32 p.i. E. risticii was detected in the blood of subclinically infected mice by the nested PCR. Twenty-two clinical specimens were seropositive for E. risticii by the IFA test, with titers ranging from 1:20 to 1:1,280. E. risticii was cultured from 95% (20 of 21) of seropositive clinical blood specimens. E. risticii was detected in the blood by PCR in 81% (17 of 20) of the culture-positive clinical specimens. The study indicated that the nested PCR is as sensitive as culture for detecting infection with E. risticii.

Objective: To determine the seroprevalence of serum antibodies to Sarcocystis neurona in horses residing in Ohio., Design: Prevalence survey., Sample Population: Serum from samples from 1,056 horses. Serum was collected on every 36th sample submitted to the Ohio State Diagnostic Laboratory for testing for equine infectious anemia., Procedure: Serum was frozen at -80 C and analyzed for antibodies to S neurona, using a western blot. Information regarding blood sample collection, age, breed, sex, and geographic location was recorded for each horse. Data were analyzed, using multivariable logistic regression., Results: Horses of 37 breeds from 81 of Ohio's 88 counties were included in the study population. There were 481 females, 133 males, and 442 geldings ranging in age from 3 months to 27 years; > 48% were < 5.6 years old. More than 53% of samples were seropositive for antibodies to S neurona. A gender or breed effect on seroprevalence was not identified. There was a significant effect of age (P < or = 0.0001; with older horses more likely to be affected), and of location (statistical and extension districts; P = 0.02 and P = 0.03, respectively) on seroprevalence. Location effects appeared to be correlated to the number of days with temperatures below freezing (P < 0.05)., Clinical Implications: The high seroprevalence of antibodies to S neurona found in the sample population emphasizes the importance of examining CSF for S neurona-specific antibodies when establishing a diagnosis of equn protozoal myeloencephalitis.

The clinical and clinicopathologic characteristics of fatal necrotizing enterocolitis were examined in 16 horses (age 4 months to 12 years). At initial presentation, 8 of 16 horses were pyrexic (median temperature, 38.4 degrees C; range, 33.8 to 40.6 degrees C); all 16 were tachycardic (median heart rate, 93 bpm, range, 66 to 138 bpm); 13 of 16 were tachypneic (median heart rate, 36 bpm, range, 16 to 80 bpm), dehydrated, and had discolored mucous membranes. All horses that were pyrexic were also tachycardic and tachypneic. PCV was high (> 45%) in 14 horses. Six horses were leukopenic (< 5,000 cells/microL); 12 were neutropenic (< 2,300 cells/microL), and 14 had > 100 band neutrophils/microL. Twelve horses were acidemic (pH < 7.37; range, 6.88 to 7.33) and the venous bicarbonate concentration was low (< 23 mEq/L) in 14 horses. Median anion gap in 16 horses was 31.5 mEq/L (> 15 mEq/L in 15 horses). Eleven of 16 horses were hyponatremic (< 137 mEq/L), 1 horse was hypernatremic (> 143 mEq/L), 3 were hypokalemic (< 3.2 mEq/L), 6 were hyperkalemic (> 4.5 mEq/L), and 14 were hypochloremic (< 98 mEq/L). Serum creatinine concentrations were high (> 1.4 mg/dL) in 15 horses. Abdominal fluid was examined in 12 horses 4 had total protein concentrations > 2.5 g/dL and 6 had nucleated cell counts > 5,000/ microL and < 10,000/microL; none had > 10,000/microL. Eight of 12 samples revealed a nondegenerate neutrophilia (> 50%). Abdominal fluid collected from 4 horses immediately before death was normal in 2 horses and indicative of suppurative inflammation in 2. All 8 horses tested had low or nonexistent serum immunofluorescent antibody titers to Ehrlichia risticii. Four of 16 horses had Salmonella spp isolated from feces or tissues. All 16 horses either died (5 of 16; 31%) or were euthanized because of a grave prognosis. Median time to death was 45.5 hours (range, 7 to 113 hours) from the time of admission. Death was preceded by severe abdominal pain in 14 horses. Fatal necrotizing enterocolitis of horses is characterized by a brief course, profound dehydration, electrolyte derangements, acid-base abnormalities, and terminally, severe abdominal pain. Abdominal fluid analysis was frequently not indicative of the severity of disease.