Atypical Myopathy Cases Research Articles

Large-scale study of blood markers in equine atypical myopathy reveals subclinical poisoning and advances in diagnostic and prognostic criteria

Equine atypical myopathy (AM) is a severe rhabdomyolysis syndrome primarily caused by hypoglycin A (HGA) and methylenecyclopropylglycine protoxins. This study aimed to refine diagnostic and prognostic criteria for AM while exploring apparently healthy cograzers. Blood samples from 263 horses, including AM cases (n= 95), cograzers (n= 73), colic horses (n= 19), and controls (n= 76), were analyzed for HGA, its toxic metabolite, and acylcarnitines profile. Diseased horses exhibited alterations in acylcarnitines that strongly distinguished them from controls and colic horses. Regression analyses identified distinct acylcarnitines profiles among groups, with cograzers showing intermediate alterations. Age and gelding status emerged as protective factors against AM. Furthermore, serum acylcarnitines profiling was valuable in predicting AM survival, with isovaleryl-/2-methylbutyrylcarnitine (i.e., C5 acylcarnitine) showing promise as both a diagnostic and prognostic marker. Subclinical alterations in cograzers underscore a novel aspect: the presence of subclinical cases of AM.

Tissue Specific Distribution and Activation of Sapindaceae Toxins in Horses Suffering from Atypical Myopathy.

Equine atypical myopathy is caused by hypoglycin A (HGA) and methylenecyclopropylglycine (MCPrG), the known protoxins of sycamore maple (Acer pseudoplatanus). Various tissues from five atypical myopathy cases were analyzed but only HGA was found. Whether deamination of MCPrG has already occurred in the intestine as the first stage of metabolization has not been investigated. Activation of the protoxins to methylenecyclopropylacetyl (MCPA)-CoA and methylenecyclopropylformyl (MCPF)-CoA, respectively, occurred mainly in the skeletal muscles, as evidenced by very high concentrations of MCPA-carnitine and MCPF-carnitine in this tissue. Inhibition of the acyl-CoA dehydrogenases of short- and medium-chain as well as branched-chain fatty acids by the toxins led to a strong increase in the corresponding acylcarnitines, again preferentially in skeletal muscles. An accumulation of the long-chain acylcarnitines beyond the level of the control samples could not be detected in the tissues. As a high amount of HGA was always found unmetabolized in the organs, we speculate that targeting the interruption of further metabolization might be a way to stop the progression of intoxication. Inhibition of the mitochondrial branched-chain amino acid aminotransferase, i.e., the first enzyme responsible for the activation of sycamore maple protoxins, could be a therapeutic approach.

In Vitro Assays for the Assessment of Impaired Mitochondrial Bioenergetics in Equine Atypical Myopathy.

Equine atypical myopathy is a seasonal intoxication of grazing equids. In Europe, this poisoning is associated with the ingestion of toxins contained in the seeds and seedlings of the sycamore maple (Acer pseudoplatanus). The toxins involved in atypical myopathy are known to inhibit ß-oxidation of fatty acids and induce a general decrease in mitochondrial respiration, as determined by high-resolution respirometry applied to muscle samples taken from cases of atypical myopathy. The severe impairment of mitochondrial bioenergetics induced by the toxins may explain the high rate of mortality observed: about 74% of horses with atypical myopathy die, most within the first two days of signs of poisoning. The mechanism of toxicity is not completely elucidated yet. To improve our understanding of the pathological process and to assess therapeutic candidates, we designed in vitro assays using equine skeletal myoblasts cultured from muscle biopsies and subjected to toxins involved in atypical myopathy. We established that equine primary myoblasts do respond to one of the toxins incriminated in the disease.

Grazing Mares on Pasture with Sycamore Maples: A Potential Threat to Suckling Foals and Food Safety through Milk Contamination.

Simple SummaryEquine atypical myopathy is seasonal poisoning resulting from the ingestion of seeds and seedlings of the sycamore maple that contains toxins. Literature mentions several cases of intoxication among gravid mares and in unweaned foals. The objective of this study was to determine whether the toxins responsible for atypical myopathy could pass to the foal via suckling. Four mares that were pasturing with sycamore in the vicinity were milked. Analysis revealed the presence of toxins in milk. This unprecedented observation could partially explain cases of unweaned foals suffering from atypical myopathy. However, a transplacental transfer of the toxin cannot be excluded for newborn cases. Besides being a source of contamination for offspring, milk contamination by toxins from fruits of trees of the Sapindaceae family might constitute a potential risk for food safety regarding other species’ raw milk or dairy products.Equine atypical myopathy (AM) is seasonal intoxication resulting from the ingestion of seeds and seedlings of the sycamore maple (Acer pseudoplatanus) that contain toxins, among them, hypoglycin A (HGA). Literature mentions several cases of AM among gravid mares and in unweaned foals. The objective of this study was to determine whether HGA and/or its metabolite are present in milk from grazing mares exposed to sycamore maple trees as confirmed by detection of HGA and its metabolite in their blood. Four mare/foal couples were included in the study. Both HGA and its metabolite were detectable in all but one of the milk samples. To our knowledge, this is the first study describing transfer of HGA to the milk. This unprecedented observation could partially explain cases of unweaned foals suffering from AM. However, a transplacental transfer of the toxin cannot be excluded for newborn foals. Besides being a source of contamination for offspring, milk contamination by toxins from fruits of trees of the Sapindaceae family might constitute a potential risk for food safety regarding other species’ raw milk or dairy products.

Detection of hypoglycin A and MCPA‐carnitine in equine serum and muscle tissue: Optimisation and validation of a LC‐MS–based method without derivatisation

Measurement of hypoglycin A (HGA) and its toxic metabolite, methylenecyclopropylacetic acid (MCPA), in equine serum confirms a diagnosis of atypical myopathy (AM), a pasture-associated toxic rhabdomyolysis with high mortality linked to the ingestion of Acer trees plant material. Supportive diagnostic tests include plasma acyl-carnitine profiling and urine organic acid testing, but these are not specific for AM. Previously reported HGA and MCPA analytical techniques used liquid chromatography-mass spectrometry (LC-MS) with a derivatising step, but the latter prolongs testing and increases costs. To develop a rapid LCMS method for detection of serum and tissue HGA and MCPA that enables expedited diagnosis for horses with AM. Analytical test validation. Validation parameters to industry standards using as criteria precision, accuracy, linearity, reproducibility and stability in analyte-spiked samples were calculated on 9-calibration points and 3 different validation concentrations in both serum and muscle tissue. The test was successfully validated for the detection of HGA and MCPA-carnitine in equine serum and muscle. Test linearity was excellent (r2 =.999), accuracy was very good for both analytes (93%-108%), precision did not exceed 10% coefficient of variation and reproducibility met the requirements of the Horwitz equation. Stability was unaffected by storage at a range of temperatures. The spectrum of the tested analytes was limited to only two relevant analytes in favour of a quick and easy analysis. Linearity of the muscle method was not evaluated as calibration curves were not produced in this matrix. We report an optimised, simplified and validated method for detection of HGA and MCPA-carnitine in equine serum and muscle suitable for rapid diagnosis of suspected AM cases. The serum-based test should also enable risk assessment of toxin exposure in cograzing horses and assessment of horses with undiagnosed myopathies, while the tissue detection test should help to confirm cases post-mortem and to determine toxin distribution, metabolism and clearance across different tissues.

Atypical myopathy in the South‐East of England: Clinicopathological data and outcome in hospitalised horses

SummaryThis retrospective case series describes clinicopathological data and outcome of hospitalised atypical myopathy (AM) cases in the South‐East of England. The study aimed to describe the frequency of metabolic abnormalities (hyperglycaemia, hyperlactataemia, hypertriglyceridaemia) and outcome in AM cases in the South‐East of England and test the hypothesis that serum creatine kinase (CK) activity and blood glucose, lactate and triglyceride concentrations are associated with outcome. Medical records (2011–2017) from three referral hospitals were reviewed for cases with a clinical diagnosis of AM. A previously described algorithm was applied and cases were included if a diagnosis of AM was considered highly likely. In cases admitted after 2013 known or possible exposure to sycamore trees was also required for inclusion. Sixty‐four animals were included, 44% (28/64) survived. Hyperglycaemia, hyperlactataemia and hypertriglyceridaemia were present in 76%, 89% and 92% of horses on admission, respectively. Survivors had lower blood lactate concentrations (survivors: median 3.5 mmol/L; range 0.5–10.4 mmol/L vs. nonsurvivors: median 7.3 mmol/L; range 2.5–16.5 mmol/L; P = 0.011) and serum CK activities (survivors: median 38,369 U/L; range 7024–570,498 U/L vs. nonsurvivors: median 172,687 U/L; range 2036–570,953 U/L; P = 0.027) on admission when compared to nonsurvivors. Increasing CK activity (P = 0.008) and triglyceride concentrations (P = 0.038) during hospitalisation were associated with nonsurvival. More nonsurvivors required sedation (18/29; 62.1% vs. 4/22; 18.2%; P = 0.002). The prognosis for hospitalised horses with AM is guarded and outcome in this population was associated with admission CK activity and lactate concentrations, and increasing CK activity and triglyceride concentrations and need for sedation during hospitalisation.

Development and validation of an ultrahigh performance liquid chromatography-high resolution tandem mass spectrometry quantification method for hypoglycin A and methylene cyclopropyl acetic acid carnitine in horse serum in cases of atypical myopathy.

Atypical myopathy (AM) is a fatal disease in horses presumably caused by hypoglycine A (HGA) from ingested maple seeds and its active metabolite methylene cyclopropyl acetic acid (MCPA). The aim of this study was the development and validation of a rapid and simple assay for HGA and MCPA-carnitine in horse serum and its application to authentic samples. Identification and quantification were carried out by ultra high performance liquid chromatography-high resolution tandem mass spectrometry (UHPLC-HRMS/MS) with full-scan/data-dependent MS/MS. Chromatographic separation was performed by isocratic elution on a hydrophilic interaction liquid chromatography (HILIC) column (100 x 2.1mm, 1.7μm). Serum samples (250μL) were worked up by protein precipitation. The method was validated according to international guidelines with respect to selectivity, linearity, accuracy, precision, matrix effects, and recovery. The calibration range was from 100 to 2000ng/mL for HGA and from 10 to 1000ng/mL for MCPA-carnitine. HGA and MCPA-carnitine showed acceptable accuracy and precision (bias -3.0% to 1.1%; RSD 9.2% to 12.4%). The limit of quantification (LOQ) was defined as the lowest calibrator and well below the lowest published serum concentrations in affected horses. Matrix effects ranged from -79% to +20% (RSD 4.2% to 14.4%), recoveries from 17.9% to 21.1% (RSD 2.3% to 10.8 %) for low and high quality control samples, respectively. Applicability was tested in 10 authentic AM cases. In all specimens, relevant amounts of HGA and MCPA-carnitine were found (570-2000ng/mL; ~8.5-150ng/mL, respectively). The developed assay allows reliable identification and quantification of HGA and MCPA-carnitine in horse serum and will be helpful to further study the association between HGA/MCPA and AM.

Equine atypical myopathy in the UK: Epidemiological characteristics of cases reported from 2011 to 2015 and factors associated with survival.

Equine atypical myopathy (AM) is a toxic rhabdomyolysis associated with ingestion of hypoglycin A, derived typically in Europe, from Acer pseudoplatanus tree. Despite the wide distribution of this tree species in the UK, the number of cases reported annually varies, and there has been an apparent increase in prevalence in recent years. Although AM was first recognised in the UK, epidemiological studies have never been conducted focused solely on this country. To describe the spatiotemporal distribution, presentation, treatment and outcome of AM cases reported in the UK. Retrospective case series. British AM cases reported to the atypical myopathy alert website, between 2011 and 2015 were included (n = 224). Data were obtained via standardised epidemiological questionnaires from owners and veterinarians. Factors associated with survival were assessed using logistic regression. Most cases reported were from England (87.9%). Survival was 38.6% (n = 73/189). Clinical factors associated with reduced odds of survival included, hypothermia (odds ratio [OR] 0.18; 95% confidence interval [CI] 0.06-0.57; P = 0.01), bladder distension (OR 0.11; CI 0.02-0.59; P = 0.01), tachycardia (OR 0.97; CI 0.94-0.99; P = 0.04) and serum creatine kinase activity >100,000 IU/L (OR 0.17; CI 0.04-0.68; P = 0.01) in the univariable analysis as well as recumbency. The latter was the only sign retained in multivariable analysis (OR = 0.19; CI 0.06-0.62; P = 0.006). Administration of vitamins during the disease was associated with survival (OR 3.75; CI 1.21-11.57; P = 0.02). Reporting cases to the Atypical Myopathy Alert Group is voluntary; therefore, under-reporting will result in underestimation of AM cases; furthermore, direct owner-reporting could have introduced misdiagnosis bias. Some areas of the UK reported AM cases more commonly. Clinical signs such as recumbency, rectal temperature, distended bladder and serum creatine kinase activity might be useful prognostic indicators though should be considered in the context of the clinical picture. Treatment with vitamins increases odds of survival.

Hypoglycin A Concentrations in Maple Tree Species in the Netherlands and the Occurrence of Atypical Myopathy in Horses.

BackgroundAtypical myopathy (AM) in horses is caused by the plant toxin hypoglycin A, which in Europe typically is found in the sycamore maple tree (Acer pseudoplatanus). Owners are concerned about whether their horses are in danger if they graze near maple trees.Hypothesis/ObjectivesTo measure hypoglycin A in the most common maple tree species in the Netherlands, and to determine whether concentration of toxin is a predictor of AM in horses.MethodsA total of 278 samples of maple tree leaves, sprouts, and seeds were classified by species. Mean concentrations of hypoglycin A were compared for the type of sample, the season and the occurrence of AM in the pasture (non‐AM versus AM). Statistical analysis was performed using generalized a linear model (SPPS22).ResultsAlmost all Acer pseudoplatanus samples contained hypoglycin A, with concentrations differing significantly among sources (P < .001). Concentrations were significantly higher in seeds from the AM group than in seeds from the non‐AM group (856 ± 677 and 456 ± 358 mg/kg, respectively; P = .039). In sprouts and leaves this was not the case. Acer platanoides and Acer campestre samples did not contain detectable concentrations of hypoglycin A.Conclusions and clinical importance Acer platanoides and campestre seem to be safe around paddocks and pastures, whereas almost all Acer pseudoplatanus samples contained hypoglycin A. In all AM cases, Acer pseudoplatanus was found. Despite significantly higher concentration of hypoglycin A in seeds of pastures where AM has occurred, individual prediction of AM cannot be made by measuring these concentrations because of the high standard deviation.

Detection of hypoglycin A in the seeds of sycamore (Acer pseudoplatanus) and box elder (A. negundo) in New Zealand; the toxin associated with cases of equine atypical myopathy

CASE HISTORY AND CLINICAL FINDINGS: During April and May 2014 four horses aged between 5 months and 9 years, located in the Canterbury, Marlborough and Southland regions, presented with a variety of clinical signs including recumbency, stiffness, lethargy, dehydration, depression, and myoglobinuria suggestive of acute muscle damage. Two horses were subjected to euthanasia and two recovered. In all cases seeds of sycamore maple (Acer pseudoplatanus) or box elder (A. negundo) were present in the area where the horse had been grazing.LABORATORY INVESTIGATION: The samaras (seeds) of some Acer spp. may contain hypoglycin A, that has been associated with cases of atypical myopathy in Europe and North America. To determine if hypoglycin A is present in the samaras of Acer spp. in New Zealand, samples were collected from trees throughout the country that were associated with historical and/or current cases of atypical myopathy, and analysed for hypoglycin A. Serum samples from the four cases and four unaffected horses were analysed for the presence of hypoglycin A, profiles of acylcarnitines (the definitive diagnosis for atypical myopathy) and activities of creatine kinase and aspartate aminotransferase.Markedly elevated serum activities of creatine kinase and aspartate aminotransferase, and increased concentrations of selected acylcarnitines were found in the case horses. Hypoglycin A was detected in the serum of those horses but not in the healthy controls. Hypoglycin A was detected in 10/15 samples of samaras from sycamore maple and box elder from throughout New Zealand.DIAGNOSIS: Cases of atypical myopathy were diagnosed on properties where samaras containing hypoglycin A were also found.CLINICAL RELEVANCE: Sycamore and box elder trees in New Zealand are a source of hypoglycin A associated with the development of atypical myopathy. If pastured horses present with clinical and biochemical signs of severe muscle damage then the environment should be checked for the presence of these trees. Horses should be prevented from grazing samaras from Acer spp. in the autumn.

Samaras and seedlings of Acer pseudoplatanus are potential sources of hypoglycin A intoxication in atypical myopathy without necessarily inducing clinical signs.

Ingestion of sycamore seeds (Acer pseudoplatanus) is the likely source of hypoglycin A in atypical myopathy (AM) but ingestion of seedlings in spring might also contribute to intoxication. To test for hypoglycin A in seeds and seedlings collected on pastures where AM cases were reported and compare its concentration in serum of affected and healthy horses. Field investigation of clinical cases. Whenever present, samaras (the winged nuts that each contain one seed) and/or seedlings were collected from pastures of 8 AM cases and 5 unaffected horses from different premises. Two AM cases were each co-grazing with an apparently healthy horse. Acylcarnitines and hypoglycin A were quantified in blood samples of all horses involved in the study. Hypoglycin A was detected in serum of AM (5.47 ± 1.60 μmol/l) but not in healthy controls pasturing where A. pseudoplatanus trees were not present. However, hypoglycin A was detected at high concentrations (7.98 μmol/l) in serum of a clinically healthy horse grazing a pasture with seedlings and samaras and also in the 2 healthy horses co-grazing with AM cases (0.43 ± 0.59 μmol/l). Hypoglycin A was detected in all samples of seeds and spring seedlings of A. pseudoplatanus. Atypical myopathy can be associated with the ingestion of sycamore samaras and also ingestion of seedlings. Hypoglycin A can be detected in the blood of horses with no detectable clinical signs at pasture in which there is A. pseudoplatanus. Determination of hypoglycin A concentration in blood is useful for screening for exposure in suspected cases of AM.

Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015.

Hypoglycin A (HG) appears to cause atypical myopathy (AM), but to our knowledge, detection of HG in affected and unaffected horses and concurrently in plants that they were exposed to has not previously been reported. To investigate HG in samples from horses exposed to Acer pseudoplatanus (European sycamore maple) and in such plant material, at the time of clinical cases of AM in the herd. Cross-sectional study. Blood was collected from 2 horses with AM and 22 clinically healthy co-grazing horses in 2 Swedish farms within one week of onset of signs (May 2014) and one month later, after horses were moved to other pastures. Ten healthy control horses from unaffected farms were sampled once. Samaras, seedlings, flowers and leaves from Acer pseudoplatanus and from Acer platanoides L (Norway maple) were collected from affected pastures. Hypoglycin A was analysed using chemical derivatisation with dansyl chloride (DNS) and ultra high performance liquid chromatography-tandem mass spectrometry. Hypoglycin A was detected as derivatised compound HG-DNS [M+H]+ with selected reaction monitoring. Hypoglycin A was detected in the horses affected with AM, and also in 20 out of 22 co-grazing horses. One month later, a surviving case horse and 9/20 co-grazing horses were still positive for HG. Controls from other farms were negative for HG. Hypoglycin A was detected in plant material from Acer pseudoplatanus, but not from Acer platanoides L. Horses grazing in pastures with HG-containing Acer pseudoplatanus were positive for HG in blood, and some showed severe signs of myopathy. Ethical animal research: Ethical consent for blood sampling was granted (C113/11) and horse owners gave their informed consent to inclusion of horses in the study. National Veterinary Institute, Sweden. Competing interests: None declared.

Hypoglycin A concentrations in seeds of Acer pseudoplatanus trees growing on atypical myopathy-affected and control pastures.

BackgroundHypoglycin A, found in seeds of Acer negundo, appears to cause seasonal pasture myopathy (SPM) in North America and is implicated in atypical myopathy (AM) in Europe. Acer negundo is uncommon in Europe. Thus, the potential source of hypoglycin A in Europe is unknown.Hypothesis and ObjectivesWe hypothesized that seeds of Acer pseudoplatanus were the source of hypoglycin A in Europe. Our objective was to determine the concentration of hypoglycin A in seeds of A. pseudoplatanus trees located in pastures where previous cases of AM had occurred.AnimalsNone.MethodsUniversity of Berne records were searched to retrospectively identify 6 farms with 10 AM cases and 11 suspected AM deaths between 2007 and 2011. During October 2012, A. pseudoplatanus seeds were collected from 2 to 6 trees per pasture on 6 AM farms (7 pastures) from trees in or close to 2 pastures on 2 control farms where AM had not been previously reported. Hypoglycin A in seeds was analyzed by GC–MS.Results Acer pseudoplatanus trees were identified on all AM pastures. Hypoglycin A was detected in all A. pseudoplatanus seeds in highly variable concentrations ranging from 0.04 to 2.81 μg/mg (mean 0.69) on AM farms and 0.10 to 9.12 μg/mg (mean 1.59) on control farms.Conclusion and Clinical ImportancePreventing horses from grazing pastures containing A. pseudoplatanus seeds during late fall and early spring might be the best means to prevent AM.

Traditional and Quantitative Assessment of Acid‐Base and Shock Variables in Horses with Atypical Myopathy

Descriptions of acid-base disturbances in atypical myopathy (AM) are limited. Describe and compare traditional and quantitative acid-base abnormalities and cardiovascular shock status in horses with AM at admission. 34 horses with AM, 15 healthy controls. Retrospective case-control study. Records were searched for shock variables (packed cell volume [PCV], blood urea nitrogen [BUN], heart and respiratory rate) and acid-base variables (venous blood gas analysis, electrolytes, total protein, lactate) on admission. Base excess (BE) of free water (BEfw), chloride (BEcl), total protein (BEtp), and unidentified anions (BEua), anion gap (AG), measured strong ion difference (SIDm), and concentration of total nonvolatile weak acids ([Atot]) were calculated. Acid-base classifications, using simplified strong ion model and traditional approach, and shock grades were assigned. A 2-sample Wilcoxon rank-sum test and Bonferroni correction compared variables in AM cases versus control horses. Significance was P < .05/16 for acid-base and P < .05/5 for shock variables. Tachycardia, tachypnea, and normal to increased PCV and BUN were common in AM cases. Respiratory, metabolic acid-base alterations, or both were mainly caused by respiratory alkalosis, lactic acidosis, and SIDm alkalosis, alone or in combination. Evaluated variables (except pH, potassium concentration, total protein, and related calculations) were significantly different (P < .001) between AM cases and control horses. The strong ion model provided a more accurate assessment than the traditional approach and identified mixed derangements. Acid-base derangements should be evaluated in horses with AM and this preferably with the strong ion model.

European outbreaks of atypical myopathy in grazing equids (2006–2009): Spatiotemporal distribution, history and clinical features

Improved understanding of the epidemiology of atypical myopathy (AM) will help to define the environmental factors that permit or support the causal agent(s) to exert toxicity. This European survey of AM aimed to describe spatiotemporal distribution, survival, clinical signs, circumstances in which AM develops and its different expressions between countries and over time. The spatiotemporal distribution, history and clinical features of AM cases reported to the Atypical Myopathy Alert Group from 2006 to 2009 were described. Comparisons of data from the most severely affected countries and from the large outbreaks were made with Fisher's exact and Welch's tests with Bonferroni correction. Of 600 suspected cases, 354 met the diagnostic criteria for confirmed or highly probable AM. The largest outbreaks occurred during the autumns of 2006 and 2009 in Belgium, France and Germany. For the first time, donkeys, zebras and old horses were affected, and clinical signs such as gastrointestinal impaction, diarrhoea, penile prolapse, buccal ulceration and renal dysfunction were observed. Affected horses spent >6 h/day on pastures that almost always contained or were surrounded by trees. The latency period was estimated at up to 4 days. Overall survival rate was 26%. Although differences between countries in affected breeds, body condition, horse management and pasture characteristics were recognised, the common presenting clinical signs and mortality were similar between countries. This study describes new data on case details, history and clinical course of AM that is of preventive, diagnostic and therapeutic value. However, the true impact of the findings of this study on the development of or severity of AM should be tested with case-control studies.

European outbreaks of atypical myopathy in grazing horses (2006–2009): Determination of indicators for risk and prognostic factors

Appropriate management of atypical myopathy (AM) requires the establishment of an accurate diagnosis and prognosis. Furthermore, preventive measures to avoid AM need to be refined. The aims of the study were as follows: 1) to improve the diagnosis of AM; 2) to identify prognostic predictors; and 3) to refine recommended preventive measures based on indicators of risk factors. An exploratory analysis of cases in Europe between 2006 and 2009 reported to the Atypical Myopathy Alert Group was conducted. Based on clinical data, reported cases were allocated into 2 groups: confirmed or highly probable AM (AM group; further divided into survivors and nonsurvivors); and cases with a low probability of having AM or with another final diagnosis (non-AM group). Using Welch's test and odds ratios corrected for multiple comparisons, the AM vs. non-AM groups were compared to identify indicators for diagnosis and risk factors, and survivors vs. nonsurvivors in the AM group were compared to identify prognostic factors. Sensitivity, specificity and positive and negative predictive values were calculated for specific clinical signs related to final diagnosis and outcome. From 600 reported cases, 354 AM cases (survival rate of 26%) and 69 non-AM cases were identified, while there were insufficient data to categorise the remainder. Variables valuable for diagnosing AM compared with similar diseases were as follows: presence of dead leaves and wood and/or trees on pastures; sloping pastures; full-time pasture access; no food supplementation; normal body condition; pigmenturia; normothermia; and congested mucous membranes. Nonsurvival was associated with recumbency, sweating, anorexia, dyspnoea, tachypnoea and/or tachycardia. Survival was associated with remaining standing most of the time, normothermia, normal mucous membranes, defaecation and vitamin and antioxidant therapy. This study refines the list of risk factors for AM. Clinical signs valuable for diagnosis and prognosis have been identified, enabling clinicians to improve management of AM cases.

Atypical myopathy in grazing horses: A first exploratory data analysis

Over the last decade, atypical myopathy (AM) in grazing horses has emerged in several European countries. An exploratory analysis was conducted to determine horse- and pasture-level indicators or factors associated with AM in Belgium. Belgian cases of AM confirmed by histology ( n = 57) were compared to their healthy co-grazing horses ( n = 77) and to pastured horses not involved with AM as controls ( n = 386). The pastures where confirmed cases were grazing (42 pastures; 38 sites; 44 incidences of AM) were compared with those of the controls (216 pastures; 96 sites; no incidence of AM). Statistically significant ( P ⩽ 0.05) exploratory variables, identified by means of adjusted odds ratios, suggested that indicators or factors associated with individual horses (young age, inactivity, body condition poor to normal), management practices (permanent pasturing, spreading of manure) and pasture characteristics (humid, sloping pastures, accumulated dead leaves, presence of waterway) may increase the risk of AM. Specific interventions based on these factors might help to reduce the incidence of AM.

Seasonal pasture myopathy in horses in the midwestern United States: 14 cases (1998–2005)

To determine clinical signs, diagnostic findings, tissue tremetone concentrations, and clinical outcome or postmortem findings in horses evaluated for acute severe nonexertional rhabdomyolysis initially attributed to white snakeroot toxicosis. Retrospective case series. 14 horses. Records of the University of Minnesota Veterinary Medical Center or Diagnostic Laboratory were searched from 1998 to 2005. Inclusion criteria included serum creatine kinase (CK) activity > 45,000 U/L, severe nonexertional myonecrosis of proximal postural muscles at necropsy, or signs of weakness without palpably firm muscles on physical examination. Vitamin E and selenium concentrations were measured in 6 horses; tremetone concentration was measured in 7. Clinical signs occurred during unfavorable weather conditions. Clinical signs of generalized weakness (n = 11 horses), muscle fasciculations (10), lethargy (6), and prolonged recumbency (4) were common. Serum CK activity ranged from 46,487 to 959,499 U/L (reference range, 82 to 449 U/L), and aspartate transaminase activity was > 1,500 U/L (reference range, 162 to 316 U/L). Two horses survived with aggressive antioxidant and fluid treatment. Postmortem examination revealed acute severe myonecrosis with lipid accumulation primarily in neck, proximal forelimb and hind limb, intercostal, and diaphragm muscles. Histopathologic signs of myocardial necrosis were detected in 7 horses. Vitamin E and selenium concentrations were within reference limits. Tremetone was not detected in liver or urine samples. Cases of rhabdomyolysis have been attributed to white snakeroot toxicosis; however, tremetone was not detected in any horses. Similarities exist between cases of seasonal pasture myopathy and cases of atypical myopathy in Europe.