Stephanie Valberg

Michigan State University | MSU · Department of Large Animal Clinical Sciences

Background Between 2020 and 2022, eight calves in a Nebraska herd (composite Simmental, Red Angus, Gelbvieh) displayed exercise intolerance during forced activity. In some cases, the calves collapsed and did not recover. Available sire pedigrees contained a paternal ancestor within 2–4 generations in all affected calves. Pedigrees of the calves’ da...

OBJECTIVE To investigate pseudohyperkalemia occurring in horses experiencing rhabdomyolysis when serum chemistry profiles are run on an VetScan VS2 analyzer (Abaxis). ANIMALS 18 horses with rhabdomyolysis (creatine kinase [CK] > 1,000 U/L). METHODS In 3 horses with serum CK activities > 5,800 U/L and persistent serum potassium concentrations of >...

Background Shivers in horses is characterized by abnormal hindlimb movement when walking backward and is proposed to be caused by a Purkinje cell (PC) axonopathy based on histopathology. Objectives Define region‐specific differences in gene expression within the lateral cerebellar hemisphere and compare cerebellar protein expression between Shiver...

Horses have a slow rate of muscle glycogen repletion relative to other species for unknown reasons. Our aim was to determine the expression of glucose transporters (GLUT) and genes impacting GLUT4 expression and translocation in the gluteal muscle. Five fit Thoroughbred horses performed glycogen-depleting exercises on high-starch (HS, 2869 g starch...

Coenzyme Q10 (CoQ10) is an essential component of the mitochondrial electron transfer system and a potent antioxidant. The impact of CoQ10 supplementation on mitochondrial capacities and the muscle proteome is largely unknown. This study determined the effect of CoQ10 supplementation on muscle CoQ10 concentrations, antioxidant balance, the proteome...

Well-developed musculature is important for performance yet difficult to quantify. Recently, we validated infrared 3-dimensional (3-D) photonic scanning as an accurate measure of body volume and proxy for regional muscle mass in horses. Our current objective was to determine the impact of body position on measures of lumbar (LV) and hindquarter (HQ...

Certain Standardbred racehorses develop recurrent exertional rhabdomyolysis (RER-STD) for unknown reasons. We compared gluteal muscle histopathology and gene/protein expression between Standardbreds with a history of, but not currently experiencing rhabdomyolysis (N = 9), and race-trained controls (N = 7). Eight RER-STD had a few mature fibers with...

Background Both type 1 (PSSM1) and type 2 polysaccharide storage myopathy (PSSM2) are characterised by aggregates of abnormal polysaccharide in skeletal muscle. Whereas the genetic basis for PSSM1 is known (R309H GYS1), the cause of PSSM2 in Quarter Horses (PSSM2‐QH) is unknown and glycogen concentrations not defined. Objectives To characterise th...

Selective breeding and discipline specific training has led to equine breeds adept at various athletic disciplines. Breed-specific skeletal muscle adaptations have been studied in many breeds but not Warmbloods (WB). We evaluated gluteal muscle contractile muscle fiber types and citrate synthase activity (CS), a marker for mitochondrial volume dens...

Movement disorders are defined as involuntary movements that are not due to a painful stimulus or associated with changes in consciousness or proprioception. Diagnosis involves ruling out any lameness and neurologic disease and characterizing the gait during walking backward and forward and trotting. Shivers causes abnormal hindlimb hypertonicity d...

Background The prevalence of clinical signs and factors triggering muscle atrophy and rhabdomyolysis associated with an MYH1E321G mutation in Quarter Horses and related breeds (QH) remain poorly understood. Hypothesis/Objectives Determine the prevalence and potential triggers of atrophy and stiffness in horses homozygous reference (N/N), heterozyg...

Pelvic limb movement disorders unrelated to lameness or proprioceptive ataxia have been described in horses for centuries. The two best described are Shivering and Stringhalt. Shivering is unique in that it is primarily apparent when horses are asked to walk backward, without affecting forward gaits until quite advanced. Horses exhibit abduction an...

Background Genetic tests for variants in MYOT (P2; rs1138656462), FLNC (P3a; rs1139799323 or P3b; rs1142918816) and MYOZ3 (P4; rs1142544043) genes are offered commercially to diagnose myofibrillar myopathy (MFM) and type 2 polysaccharide storage myopathy (PSSM2) in Quarter Horses (QH). Objectives To determine if PSSM2‐QH has histopathological feat...

Myosinopathies are defined as a group of muscle disorders characterized by mutations in genes encoding myosin heavy chains. Their exact molecular and cellular mechanisms remain unclear. In the present study, we have focused our attention on a MYH1-related E321G amino acid substitution within the head region of the type IIx skeletal myosin heavy cha...

We have analyzed the enzymatic activity of the sarcoplasmic reticulum (SR) Ca2+-transporting ATPase (SERCA) from the horse gluteal muscle. Horses are bred for peak athletic performance yet exhibit a high incidence of exertional rhabdomyolysis, with elevated levels of cytosolic Ca2+ proposed as a correlative linkage. We recently reported an improved...

Horses have one of the highest skeletal muscle oxidative capacities amongst mammals, which, combined with a high glycolytic capacity, could perturb redox status during maximal exercise. We determined the effect of 30 d of oral coenzyme Q10 and N-acetyl-cysteine supplementation (NACQ) on muscle glutathione (GSH), cysteine, ROS, and coenzyme Q10 conc...

Background In the Quarter Horse (QH), myosin heavy chain myopathy (MYHM), which is characterised by nonexertional rhabdomyolysis or immune‐mediated myositis (IMM) with acute muscle atrophy, is strongly associated with the missense E321G MYH1 mutation. Objectives To document the existence of MYHM in the Brazilian QH population, this study includes...

Background Myofibrillar myopathy in humans causes protein aggregation, degeneration, and weakness of skeletal muscle. In horses, myofibrillar myopathy is a late-onset disease of unknown origin characterized by poor performance, atrophy, myofibrillar disarray, and desmin aggregation in skeletal muscle. This study evaluated molecular and ultrastructu...

The coronavirus pandemic abruptly halted all in-person clerkships, or clinical rotations, for clinical veterinary students across the United States (US). Online clerkships in radiology offered the opportunity to expand the student’s ability to interpret medical images but did not allow for the development of physical hands-on imaging skills recogni...

Background Currently, there is little information regarding the concentrations of phosphorylated neurofilament heavy protein (pNfH) in the serum and cerebrospinal fluid (CSF) of horses with neurodegenerative diseases. Specifically, pNfH concentrations have not yet been evaluated in horses with equine neuroaxonal dystrophy/equine degenerative myeloe...

Skeletal muscle citrate synthase (CS) activity serves as a marker for muscle oxidative capacity. CS activity was compared among Quarter Horses (QH), Arabians (AR), Thoroughbreds (TB), Standardbreds and Warmbloods at various ages and stages of training. Gluteus medius muscle biopsies were obtained at ages 6–23 m (n = 10), 2 y (n = 37), 3 y (n = 44)...

A diagnosis of type 2 polysaccharide storage myopathy (PSSM2) in Quarter Horse-related breeds (QH) is currently based on the absence of the glycogen synthase 1 (GYS1) mutation causing type 1 PSSM (PSSM1) and presence of aggregates polysaccharide in myofibers. Recently, genetic tests for PSSM2 have been offered by a commercial company based on varia...

In the mitochondria, complexes I and III of the electron transport system (ETS) generate reactive oxygen species (ROS) during exercise that are reduced by antioxidants to mitigate oxidative stress. Among these antioxidants are thiol-based antioxidants such as glutathione as well as Coenzyme Q10 (CoQ10), which also transports electrons from complex...

Recurrent exertional rhabdomyolysis (RER) is a chronic muscle disorder of unknown etiology in racehorses. A potential role of intramuscular calcium (Ca2+) dysregulation in RER has led to the use of dantrolene to prevent episodes of rhabdomyolysis. We examined differentially expressed proteins (DEP) and gene transcripts (DEG) in gluteal muscle of Th...

Ca2+ regulation in equine muscle is important for horse performance, yet little is known about this species-specific regulation. We reported recently that horse encode unique gene and protein sequences for the sarcoplasmic reticulum (SR) Ca2+-transporting ATPase (SERCA) and the regulatory subunit sarcolipin (SLN). Here we quantified gene transcript...

We have analyzed protein expression and enzyme activity of the sarcoplasmic reticulum Ca2+-transporting ATPase (SERCA) in horse gluteal muscle. Horses exhibit a high incidence of recurrent exertional rhabdomyolysis, with myosolic Ca2+ proposed, but yet to be established, as the underlying cause. To better assess Ca2+ regulatory mechanisms, we devel...

Background Commercial genetic tests for type 2 polysaccharide storage myopathy (PSSM2) and myofibrillar myopathy (MFM) have not been validated by peer‐review, and formal regulation of veterinary genetic testing is lacking. Objectives To compare genotype and allele frequencies of commercial test variants (P variants) in MYOT (P2; rs1138656462), FLN...

There are 5 single-gene mutations that are known to cause muscle disease in horses. These mutations alter the amino acid sequence of proteins involved in cell membrane electrical conduction, muscle energy metabolism, muscle contraction, and immunogenicity. The clinical signs depend on the pathway affected. The likelihood that an animal with a mutat...

Background Myofibrillar myopathy (MFM) of unknown aetiology has recently been identified in Warmblood (WB) horses. In humans, 16 genes have been implicated in various MFM‐like disorders. Objectives To identify variants in 16 MFM candidate genes and compare allele frequencies of all variants between MFM WB and non‐MFM WB and coding variants with mo...

This chapter deals with equine musculoskeletal diseases, focusing on joint injuries and disease and osteoarthritis, bone injuries and diseases, tendon and ligament injuries and diseases, and muscle injuries and diseases. While a definitive characteristic of osteoarthritis (OA) is articular cartilage destruction, the accompanying changes of synoviti...

Reasons for performing study Although muscle mass strongly influences performance, there is currently no effective means to measure the 3-dimensional muscle mass of horses. We evaluated a 3-dimensional (3D) scanning methodology for its ability to quantify torso and hindquarter volumes as a proxy for regional muscle mass in horses. Objectives Deter...

Objective To review the veterinary literature regarding healing and complications associated with equine celiotomy including anatomy and physiology, risk factors for incisional infection and hernia, and treatment. Etiology Celiotomy is the most common approach to treat horses with surgical colic. Incision through the linea alba provides exposure t...

Background A subset of horses deficient in alpha‐tocopherol (α‐TP) develop muscle atrophy and vitamin E‐responsive myopathy (VEM) characterized by mitochondrial alterations in the sacrocaudalis dorsalis medialis muscle (SC). Objectives To quantify muscle histopathologic abnormalities in subclinical α‐TP deficient horses before and after α‐TP suppl...

Large colon volvulus (LCV) is a life-threatening form of colic that occurs when the large colon rotates 360° or more on its axis, resulting in colonic distention and ischaemia. Any horse can suffer from LCV, but the risk is greatest for periparturient Thoroughbred broodmares; the objective of this study was to estimate the heritability of LCV in th...

A 3‐year‐old Gypsy Vanner stallion was presented for evaluation of intermittent recumbency, muscle fasciculations, weakness, low head carriage, shifting of weight between the hindlimbs and an elevated tail head. History, physical examination and serum alpha tocopherol concentrations were suggestive of vitamin E deficiency and equine motor neuron di...

We conducted a retrospective cohort study to test the hypothesis that performing 4 weeks of core abdominal rehabilitation exercises (CARE) postoperatively would be safe and associated with faster return to training and improved performance after colic surgery. Performance horses that recovered from colic surgery performed by the same surgeon and su...

Background Sarcolipin (SLN), myoregulin (MRLN), and dwarf open reading frame (DWORF) are transmembrane regulators of the sarcoplasmic reticulum calcium transporting ATPase (SERCA) that we hypothesized played a role in recurrent exertional rhabdomyolysis (RER). Objectives Compare coding sequences of SLN, MRLN, DWORF across species and between RER a...

Background Immune‐mediated myositis (IMM) in American Quarter Horses (QHs) causes acute muscle atrophy and lymphocytic infiltration of myofibers. Recently, an E321G mutation in a highly conserved region of the myosin heavy chain 1 (MYH1) gene was associated with susceptibility to IMM and nonexertional rhabdomyolysis. Objectives To estimate prevale...

Supplemental Table 1 Phenotype, breed, age, sex, serum creatine kinase (CK) activity, type of analyses or gene sequenced and histopathology for horses included in sequencing and qRT‐PCR studies. Supplemental Table 2: Primers sets used for genomic sequencing of SLN, DWORF and MRLN Supplemental Table 3. Primer sets used for qRT‐PCR. Supplemental T...

Equine myofibrillar myopathy (MFM) causes exertional muscle pain and is characterized by myofibrillar disarray and ectopic desmin aggregates of unknown origin. To investigate the pathophysiology of MFM, we compared resting and 3 h post-exercise transcriptomes of gluteal muscle and the resting skeletal muscle proteome of MFM and control Arabian hors...

Type 1 polysaccharide storage myopathy (PSSM1) is a glycogen storage disorder of known cause whereas the basis for type 2 PSSM (PSSM2) is unknown. The same diet and exercise regime prescribed for PSSM1 is recommended for PSSM2; however, the benefit of these recommendations for PSSM2 is undocumented. The objectives of this study were to determine tr...

Neuromuscular Diagnostic Laboratory Polysaccharide storage myopathy. Recommendations. (PDF)

Neuromuscular Diagnostic Lab: Muscle biopsy follow-up survey. Questionnaire distributed to participants of PSSM2 WB. (PDF)

PSSM2 questionnaire data. All answers from PSSM2 questionnaire with anonymity. (XLSX)

Baseline questionnaire data. All answers from baseline questionnaire with anonymity. (XLSX)

Type 2 polysaccharide sorage myopathy. Recommendations. (PDF)

Equine Neuromuscular Diagnostic Lab: Healthy performance horse questionnaire. Questionnaire distributed to baseline WB participants. (PDF)

Skeletal muscle glycogen concentrations. (XLSX)

Background An E321G mutation in MYH1 was recently identified in Quarter Horses (QH) with immune‐mediated myositis (IMM) defined by a phenotype of gross muscle atrophy and myofiber lymphocytic infiltrates. Hypothesis/Objectives We hypothesized that the MYH1 mutation also was associated with a phenotype of nonexertional rhabdomyolysis. The objective...

A 12‐hours‐old Paint filly was examined because of weakness and dull mentation after birth. Despite IV administered dextrose, the foal remained persistently hypoglycemic with increase in serum activity of muscle and liver enzymes. A postmortem diagnosis of lipid myopathy most similar to multiple acyl‐CoA dehydrogenase deficiency (MADD) was confirme...

Optimal function of skeletal muscle is essential for successful athletic performance. Even minor derangements in locomotor muscle function will impact power output, coordination, stamina, and desire to work during exercise. In this review, the presenting clinical signs, differential diagnoses, approach to diagnostic testing and treatment of muscle...

Background: The cause of immune-mediated myositis (IMM), characterized by recurrent, rapid-onset muscle atrophy in Quarter Horses (QH), is unknown. The histopathologic hallmark of IMM is lymphocytic infiltration of myofibers. The purpose of this study was to identify putative functional variants associated with equine IMM. Methods: A genome-wide...

Background: Cerebellar Purkinje cell axonal degeneration has been identified in horses with shivering but its relationship with abnormal hindlimb movement has not been elucidated. Objectives: To characterise surface electromyographic (sEMG) hindlimb muscle activity in horses with shivering, correlate with clinical scores and examine horses for P...

OBJECTIVE To characterize clinical findings for polysaccharide storage myopathy (PSSM) in warmblood horses with type 1 PSSM (PSSM1; caused by mutation of the glycogen synthase 1 gene) and type 2 PSSM (PSSM2; unknown etiology). SAMPLE Database with 3,615 clinical muscle biopsy submissions. PROCEDURES Reported clinical signs and serum creatine kinase...

Background Efforts to resolve the transcribed sequences in the equine genome have focused on protein-coding RNA. The transcription of the intergenic regions, although detected via total RNA sequencing (RNA-seq), has yet to be characterized in the horse. The most recent equine transcriptome based on RNA-seq from several tissues was a prime opportuni...

Background: To report a novel exertional myopathy, myofibrillar myopathy (MFM), in Warmblood horses. Objectives: To 1) describe the distinctive clinical and myopathic features of MFM in Warmblood horses, 2) investigate the potential inheritance of MFM in a Warmblood family. Study design: Retrospective selection of MFM cases and prospective eva...

Background: Alpha-tocopherol (α-TP) supplementation is recommended for the prevention of various equine neuromuscular disorders. Formulations available include RRR-α-TP acetate powder and a more expensive but rapidly water-dispersible liquid RRR-α-TP (WD RRR-α-TP). No cost-effective means of rapidly increasing serum and cerebrospinal fluid (CSF) α...

The most basic aim of veterinary clinical nutrition is to design diets that prevent diseases by meeting the minimum daily requirements for essential nutrients. Two neuromuscular disorders that are impacted by nutritional deficiencies include myodegeneration due to selenium deficiency and equine motor neuron disease due to vitamin E deficiency. Equi...

In horses, immune-mediated muscle disorders can arise from an overzealous immune response to concurrent infections or potentially from an inherent immune response to host muscle antigens. Streptococcus equi ss. equi infection or vaccination can result in infarctive purpura hemorrhagica (IPH) in which vascular deposition of IgA-streptococcal M prote...

In the horse, the term occipitoatlantoaxial malformation (OAAM) is used to describe a developmental defect in which the first cervical vertebra (atlas) resembles the base of the skull (occiput) and the second cervical vertebra (axis) resembles the atlas. Affected individuals demonstrate an abnormal posture and varying degrees of ataxia. The homeobo...

Background Transcriptome interpretation relies on a good-quality reference transcriptome for accurate quantification of gene expression as well as functional analysis of genetic variants. The current annotation of the horse genome lacks the specificity and sensitivity necessary to assess gene expression especially at the isoform level, and suffers...

Specific spontaneous heritable neurodegenerative diseases have been associated with lower serum and cerebrospinal fluid α-tocopherol (α-TOH) concentrations. Equine neuroaxonal dystrophy (eNAD) has similar histologic lesions to human ataxia with vitamin E deficiency caused by mutations in the α-TOH transfer protein gene (TTPA). Mutations in TTPA are...

Background Transcriptome interpretation relies on a good-quality reference transcriptome for accurate quantification of gene expression as well as functional analysis of genetic variants. The current annotation of the horse genome lacks the specificity and sensitivity necessary to assess gene expression especially at the isoform level, and suffers...

A previous report suggests a substantial incidence of exertional rhabdomyolysis (ER) in Arabian horses performing endurance racing. This study compared formalin histopathology and clinical and metabolic responses to a standardised field exercise test (SET) between Arabians with and without ER. Arabian horses with (n = 10; age 15.4 ± 5.6 years) and...

Objective: A pigment retinopathy has been reported in adult horses with equine motor neuron disease (EMND) arising from chronic α-tocopherol (α-TP) deficiency. A pigment retinopathy has not been identified in horses with neuroaxonal dystrophy/equine degenerative myeloencephalopathy (NAD/EDM) that affects genetically susceptible young horses with α...

Background: Major histocompatibility complex (MHC) I and II expression is not normally detected on sarcolemma, but is detected with lymphocytic infiltrates in immune-mediated myositis (IMM) of humans and dogs and in dysferlin-deficient muscular dystrophy. Hypothesis/objectives: To determine if sarcolemmal MHC is expressed in active IMM in horses...

A suspicion of inflammatory myopathy in horses arises from clinical history, physical exam findings, hematologic findings, serum biochemistry profile, and bacterial cultures/PCR or serum titers. In horses, inflammatory myopathies are not as well characterized, and it is difficult to clearly discern whether myositis arises as a secondary consequence...

Figure S1. Multi‐generation pedigree of Cases 1–3 and Horse A, demonstrating relatedness between the American Paint Horse (Case 1) and EDM/EMND‐affected Thoroughbreds (Cases 2 and 3).

Table S2. Variants found in sequencing SOD1 cDNA.

Table S1. Primer sequences, melting temperatures (Tm) and product region used for SOD1 sequencing.

OBJECTIVE To compare effects of training on conventional and underwater treadmills on fiber properties and metabolic responses of the superficial digital flexor (SDF) and gluteal muscles to high-speed exercise in horses. SAMPLE 6 unconditioned Quarter Horse–type horses. PROCEDURES 6 horses were walked on underwater and conventional treadmills for 5...

This report describes a case of severe rhabdomyolysis in a pregnant mare associated with histopathologic and biochemical features of both selenium deficiency and acquired multiple acyl-CoA dehydrogenase deficiency (MADD) due to seasonal pasture myopathy (SPM). This case highlights the importance of assessing plasma selenium levels in horses with cl...

Equine degenerative myeloencephalopathy (EDM) is characterized by a symmetric general proprioceptive ataxia in young horses, and is likely underdiagnosed for 2 reasons: first, clinical signs overlap those of cervical vertebral compressive myelopathy; second, histologic lesions-including axonal spheroids in specific tracts of the somatosensory and m...

Although exertionalrhabdomyolysis (ER) is common in Arabian horses,there are no dedicated studies describing histopathologic characteristics of muscle from Arabian horses with ER. To prospectively identify distinctive histopathologic features of muscle from Arabian endurance horses with a history of ER (pro-ER) and to retrospectively determine thei...

"Shivers" is a progressive equine movement disorder of unknown etiology. Clinically, horses with shivers show difficulty walking backward, assume hyperflexed limb postures, and have hind limb tremors during backward movement that resembles shivering. At least initially, forward movements are normal. Given that neither the neurophysiologic nor the p...

6-week-old, Arabian-cross male foal was referred to the Veterinary Teaching Hospital at the Louisiana State University School of Veterinary Medicine for a 1-week history of progressive weakness and intermittent right thoracic limb lameness. The foal had a normal birth, was healthy, had been active, and had not exhibited any abnormalities of gait be...

Horses are remarkable athletes and a fascinating species in which to study the genetic bases of athletic performance, skeletal muscle biology, and neuromuscular disease. Genetic selection in horses has resulted inmany breeds that possess anatomical, physiological, and metabolic variations linked to speed, power, and endurance that are beginning to...