Sarcocystis myositis and vitamin E deficiency in a Gypsy Vanner stallion suspected of having equine motor neuron disease

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 disease (EMND). Sacrocaudalis dorsalis medialis muscle biopsy identified myositis secondary to sarcocystosis. Treatment with alpha tocopherol, ponazuril and sulfadiazine/pyrimethamine resulted in significant improvement in muscle weakness and body condition with resolution of sarcocystosis and inflammation on repeat muscle biopsy. This case illustrates the importance of muscle biopsy in horses with neuromuscular disease as concurrent diseases may be present that require specific treatment for a positive outcome.     

Prevalence of equine polysaccharide storage myopathy and other myopathies in two equine populations in the United Kingdom

The aim of this study was to determine the prevalence of equine polysaccharide storage myopathy (EPSM) in two populations of horses in the UK. Biopsy specimens from 94 horses presented to an abattoir (population 1), and 46 horses with neuromuscular disorders presented to a university referral hospital (population 2) were obtained over a period of 4 years. Histological sections were examined by a veterinary pathologist for lesions including abnormal polysaccharide inclusions in myofibres.In population 1, a diagnosis of EPSM was made in 8% and non-specific myopathy in 33% of horses. In population 2, a diagnosis of EPSM was made in 22%, equine motor neurone disease (EMND) in 15% and non-specific myopathy in 37%. Within each population there was no difference in age, sex or breed distribution and muscle disease diagnosis. However, populations differed from each other in age and breed distributions and muscle disease diagnosis. EPSM was found in draft, Warmblood and related breeds and was diagnosed for the first time in cob-types. EMND was reported in 7/46 horses presented for neuromuscular disease and weakness, representing an important diagnosis in the UK. This study showed a high prevalence of EPSM and other myopathies in typical breeds of horses in the UK.     

Association between plasma vitamin E concentration and the risk of equine motor neuron disease

Equine motor neuron disease (EMND) is a neurodegenerative disorder of the somatic lower motorneurons that results in a syndrome of diffuse neuromuscular disease in the adult horse. The aetiology of this disorder is unknown, although prior studies have suggested that a deficiency in the lipid antioxidant vitamin E (α-tocopherol) contributes to the development of EMND. This paper describes a case-control study designed to investigate the association between plasma vitamin E levels and the risk of EMND for horses. Signalment, plasma vitamin E levels at the time of referral, and information relative to dietary and management practices were collected from 53 horses diagnosed with EMND and 69 controls. The mean plasma vitamin E concentration in EMND cases was significantly lower than that of control horses. After controlling for other risk factors of EMND, there was a statistically significant association between plasma vitamin E levels and EMND, with the likelihood of the disease increasing as the vitamin E concentration decreased. These findings support the reported role of vitamin E deficiency as one of the risk factors for EMND.     

Evaluation of the risk of motor neuron disease in horses fed a diet low in vitamin E and high in copper and iron

OBJECTIVE: To determine whether equine motor neuron disease (EMND) could be induced in adult horses fed a diet low in vitamin E and high in copper and iron. ANIMALS: 59 healthy adult horses. PROCEDURE: Horses in the experimental group (n = 8) were confined to a dirt lot and fed a concentrate low in vitamin E and high in iron and copper in addition to free-choice grass hay that had been stored for 1 year. Control horses (n = 51) were fed a concentrate containing National Research Council-recommended amounts of copper, iron, and vitamin E. The hay fed to control horses was the same as that fed to experimental horses, but it had not been subjected to prolonged storage. Control horses had seasonal access to pasture, whereas experimental horses had no access to pasture. Horses that developed clinical signs of EMND were euthanatized along with an age-matched control horse to determine differences in hepatic concentrations of vitamin E, vitamin A, copper, iron, and selenium. RESULTS: 4 experimental horses developed clinical signs of EMND. Plasma concentrations of vitamin E decreased in all 8 experimental horses. There were no significant changes in plasma concentrations of vitamin A, selenium, and copper or serum concentrations of ferritin. There were no significant differences in those analytes between experimental horses with EMND and experimental horses that did not develop EMND. No control horses developed EMND. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that lack of access to pasture, dietary deficiency of vitamin E, or excessive dietary copper are likely risk factors for EMND.     

Equine botulism: A clinical approach to diagnosis and management

Botulism is a syndrome of neuromuscular weakness caused by the toxins of Clostridium botulinum. Whilst it can affect most mammals, the horse appears to be one of the more susceptible species. Intoxication can occur via ingestion of preformed toxins in spoiled foodstuffs, ingestion of spores with colonisation in the intestinal tract or the contamination of wounds by C. botulinum. Food‐borne botulism is the most common worldwide, usually associated with spoiled roughage. Both individual cases and outbreaks have been reported, with generally a poor prognosis. Many affected horses succumb to recumbency and death/euthanasia shortly after onset of signs. Botulism should be considered a differential diagnosis for any horse displaying dysphagia or symmetrical neuromuscular weakness.     

Horses on pasture may be affected by equine motor neuron disease

REASONS FOR PERFORMING STUDY: Equine motor neuron disease (EMND) was diagnosed in 3 horses maintained on lush, grass-based pasture. This contrasted with North American studies which identified limited or no access to green herbage as an important risk factor for EMND. HYPOTHESIS: Grazing horses that have an apparently adequate intake of pasture herbage to meet normal equine vitamin E requirements can develop EMND. METHODS: Owners of 32 European horses diagnosed with EMND completed a questionnaire regarding intrinsic, managemental, nutritional and environmental factors that could potentially be risk factors for EMND, and also regarding clinical signs, treatments and case outcome. Plasma/serum vitamin E data for these horses were supplied by the veterinarians. No control population was studied. RESULTS: Thirteen of 32 horses (termed the 'grazing' group) had part- or full-time access to grass-based pasture at the onset of EMND (median duration at pasture 12 h/day, range 3-24 h). Five of these horses were at pasture for at least 235 h/day at the onset of EMND, 2 of which were at pasture for at least 23.5 h/day throughout the year. Despite grazing, all these horses had a low vitamin E status. The remaining 19 horses resembled those cases reported from North America, in that they had no or limited access to pasture. CONCLUSIONS AND POTENTIAL RELEVANCE: A diagnosis of EMND should not be discounted on the basis that a horse has access, even full-time, to lush grass-based pasture. Inadequate vitamin E intake was probably not the sole cause of either the EMND or the low vitamin E status in the grazing horses; the latter was probably the result of abnormal bioavailability or excessive utilisation of vitamin E.     

Risk factors for acquired myasthenia gravis in cats: 105 cases (1986-1998)

OBJECTIVE: To determine prevalence of initial clinical signs and risk factors for acquired myasthenia gravis (MG) in cats. DESIGN: Retrospective case-control study. ANIMALS: 105 cats from the United States, Canada; and the United Kingdom with a confirmed diagnosis of acquired MG and 510 cats with other neuromuscular disorders, including generalized weakness, megaesophagus, and dysphagia (control group). PROCEDURES: Records were retrieved from a data-base containing results of serum samples tested for acetylcholine receptor antibodies. Signalment, including breed, age, and state or country of origin, month of onset, and initial clinical signs were obtained. An acetylcholine receptor antibody titer > 0.3 nmol/L was diagnostic for acquired MG. Unconditional logistic regression was used for statistical analysis. RESULTS: Compared with mixed-breed cats, the breed with the highest relative risk of acquired MG was the Abyssinian (including Somali). Significant differences between sexes were not detected. There was no compelling evidence for a difference in risk of developing MG between states or countries. Relative risk increased after 3 years of age. The most common clinical signs were generalized weakness without megaesophagus and weakness associated with a cranial mediastinal mass. Focal signs, including megaesophagus and dysphagia without signs of generalized weakness, were also evident. CONCLUSIONS AND CLINICAL RELEVANCE: A breed predisposition for acquired MG in Abyssinians (and related Somalis) was observed. Clinical signs were variable and included generalized weakness, megaesophagus, and dysphagia. A cranial mediastinal mass was commonly associated with MG in cats.     

Canine trichinosis with signs of neuromuscular disease

A six-year-old fox terrier bitch, used for badger hunting, developed acutely progressive painless disturbance of locomotion with pronounced weakness. Evidence of central nervous disease or myasthenia gravis was not present. Muscle histology revealed trichinella larvae and changes consistent with a combined inflammatory myopathy and neuropathy. An enzyme-linked immunosorbent assay (ELISA) showed significantly increased serum levels of antibodies to Trichinella spiralis antigen. It is likely that the signs of neuromuscular disease shown by the dog were due to the trichinella infection. The case illustrates that symptomatic trichinosis should be considered in the clinical workup of myopathies in dogs with access to potentially trichinella-infected wildlife.     

Ocular manifestations of equine motor neuron disease

The characteristics of the ocular manifestations of equine motor neuron disease (EMND) are described. Forty-two horses with histories, clinical signs and necropsies compatible with EMND were the subjects of this study. Ophthalmoscopic lesions that varied in severity were found in 40 of 42 horses and appeared as a distinct pigmented reticulated pattern at the tapetal-nontapetal junction or throughout the fundus, depending upon severity. The pattern colours ranged from yellow brown to black. Areas of hyperreflectivity formed mosaic patterns in the tapetal fundus. ERG B-wave amplitudes were usually at least 50% reduced and many animals showed extinguished amplitudes. None of the horses had apparent visual impairment. Histopathologically, all 42 horses had retinal pigment epithelial (RPE) congestion with ceroid-lipofuscin. Retinal degeneration was variable even within the eyes. Thin layer chromatography (TLC) analysis of the RPE and neural retina identified both green and orange emitting fluorescent compounds not found in normal horses. All unsupplemented horses had plasma vitamin E levels <1.0 microg/ml. The potential significance of this report is the pathognomonic role the ocular manifestations exhibit in helping to diagnose equine motor neuron disease.     

Concentrations of trace minerals in the spinal cord of horses with equine motor neuron disease

OBJECTIVE: To compare concentrations of trace minerals in the spinal cord of horses with equine motor neuron disease (EMND) with those of horses without neurologic disease (control horses). ANIMALS: 24 horses with EMND and 22 control horses. PROCEDURE: Spinal cord trace mineral concentrations in horses with EMND and control horses were analyzed by use of inductively coupled plasma atomic emission spectroscopy (calcium, phosphorus, sodium, potassium, magnesium, copper, iron, manganese, nickel, zinc, aluminum, cobalt, and chromium), atomic absorption spectrophotometry (lead and cadmium), flameless atomic absorption (mercury), and fluorometry (selenium). RESULTS: Copper concentration was significantly higher in the spinal cord of horses with EMND, compared with control horses; spinal cord concentrations of all other trace minerals were similar between groups. CONCLUSION AND CLINICAL RELEVANCE: Among spinal cord trace minerals investigated in the study, only copper concentrations were significantly different between horses with EMND and horses without neurologic disease, which suggests that copper may be involved in the pathogenesis of EMND. An hypothesis of oxidative injury in this disease is supported by the finding of increased copper concentrations in the spinal cord and by low vitamin E concentrations reported by other researchers.     

Tick toxicity in cats caused by Ixodes species in Australia: a review of published literature

Tick toxicity in cats caused by Ixodes holocyclus and related species is a common medical condition on the east coast of Australia. Intoxication typically causes a flaccid ascending neuromuscular paralysis and clinical signs can include anxiety, dysphonia, hind limb weakness and/or ataxia, pupillary dilation, respiratory signs and possible bladder voiding dysfunction. Diagnosis is made with a combination of appropriate clinical signs and visualisation of tick(s) on a thorough body search. Cases are classified clinically using a scoring system, which grades neuromuscular weakness and respiratory compromise. The mainstays of treatment are tick removal, administration of tick antitoxin serum and intensive supportive care. Given a prompt and appropriate management regimen, prognosis is good, according to available literature. Most of the literature concerning tick toxicity in cats is anecdotal in nature and an evidence-based review of what is known of this condition has not previously been published.     

Differential expression of TAR DNA-binding protein (TDP-43) in the central nervous system of horses afflicted with equine motor neuron disease (EMND): a preliminary study of a potential pathologic marker

Equine motor neuron disease (EMND) is a neurodegenerative disorder of unknown etiology affecting horses worldwide. Trans-Active Response DNA Binding Protein of 43?kDa (TDP-43) has been reported in the central nervous system (CNS) of several neurodegenerative conditions in humans including Amyotrophic Lateral Sclerosis (ALS) and assumed to play role in the disease. We examined whether horses afflicted with EMND express the TDP-43 in CNS. Ten horses with EMND and 6 controls of different ages and breed we enrolled. Detection of presence of TDP-43 protein in the CNS was analyzed by immunohistochemical staining using rabbit anti-human TARDBP (TDP-43) polyclonal antibody. Formalin fixed neuronal tissues from medulla, cervical, and lumbar spinal cord were harvested from EMND and from control horses. Sections were assigned randomly to TDP-43 treated or rabbit anti-IgG as control. Nuclear staining of TDP-43 was detected in one of the neural tissues of 75?% of EMND-positive and 0 of 0?% of control horses in the central nervous system (medulla, and/or cervical spinal cord and/or lumbar spinal cord). TDP-43 antibody was detected in the nucleus of EMND horses and no cytoplasmic staining was noted. As in ALS, there was no pattern of age clustering associated with the detection of TDP-43. This is the first report on the staining of TDP-43 in neuronal tissues of horses and suggests that TDP-43 may play a role in the pathogenesis of EMND. Further studies are needed to elucidate the etiologic role of this protein in the diseases.     

Staggers in sheep associated with the ingestion of Tributes terrestris

The history of an unusual locomotory disturbance of sheep is traced from its first recognition in 1937 through to the most recent outbreak in 1981-83. The condition occurred only at certain times and in restricted areas of the central and northern slopes districts of New South Wales. Outbreaks were repeatedly associated with drought periods during which sheep grazed large areas of Tribulus terrestris for many months at a time. Many thousands of sheep were affected, but the prevalence varied greatly between flocks. The course of the disease was characterised by a slowly developing, irreversible, asymmetrical, weakness of the hindlimbs. The clinical signs suggested that a lesion of the thoraco-lumbar spinal cord region was present. The macroscopic and microscopic examination of the nervous and musculoskeletal systems failed to demonstrate abnormalities which would account for the clinical signs. Haematological, biochemical and toxicological test results supported the concept of a neuromuscular disease process being present, but failed to indicate its aetiology.     

Evaluation of glucose tolerance and intestinal luminal membrane glucose transporter function in horses with equine motor neuron disease

OBJECTIVE: To confirm whether the plasma glucose concentration curve obtained during oral glucose tolerance tests (OGTTs) in horses with equine motor neuron disease (EMND) is decreased, compared with that obtained in clinically normal horses, and determine whether that decrease is a result of defective glucose metabolism or intestinal glucose transport dysfunction. ANIMALS: 8 horses with EMND and 44 matched control horses. PROCEDURE: Electromyography and OGTTs were performed in all 8 affected horses and 10 control horses. Intravenous GTTs (IVGTTs) were performed in 6 affected horses and another 11 control horses. The activity and levels of jejunal luminal membrane glucose transporter (Na+ / glucose cotransporter isoform 1 [SGLT1]) were measured in 2 affected horses and 23 control horses. RESULTS: In horses with EMND, generalized neuropathy was detected via quantitative electromyography; the mean increase in plasma glucose concentration during the OGTT was significantly decreased, compared with the value in control horses. During the IVGTT the mean increase in plasma glucose concentration was significantly lower than that of control horses. The activity and levels of SGLT1 in 2 affected horses were similar to those of control horses. Diagnosis of EMND was confirmed postmortem in all affected horses. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggest that the decreased plasma glucose curve obtained in horses with EMND during OGTTs (compared with control horses) is a result of overall enhanced glucose metabolism or abnormalities in the facilitated glucose transporters; definitive identification of the underlying mechanisms could aid in the development of appropriate treatments of EMND in horses.     

Acquired Myasthenia Gravis

Serum samples from 152 dogs with a clinical diagnosis of idiopathic megaesophagus without detectable generalized muscle weakness were tested for the presence of antibodies to acetylcholine receptors by immunoprecipitation radioimmunoassay. Positive serum antibody titers (mean, 3.1 nmoL/L; range, 0.77-30 nmoL/L; reference values less than 0.6 nmoL/L) were found in 40 dogs (26%), with German Shepherd dogs (8/25, 32%) and Golden Retrievers (7/20, 35%) having a greater percentage of positive submissions. By immunocytochemical methods, localization of immune complexes at the neuromuscular junction after incubation of serum with normal canine muscle was documented in an additional 17 cases (11% of all samples submitted) that did not have increased antibody titers to acetylcholine receptors. Of the 40 seropositive dogs, 17 (48%) had a clinical improvement or remission of clinical signs associated with decreasing AChR antibody titers. Idiopathic megaesophagus has been associated with a poor prognosis; however, this study demonstrates that a large percentage of the dogs have myasthenia gravis and that with supportive treatment, the clinical signs may improve or resolve.     

Perception of Equine Practitioners Regarding the Occurrence of Selected Equine Neurologic Diseases in the Northeast Over a 10-Year Period

A survey was developed to examine the perception of equine practitioners regarding the occurrence of five equine neurologic diseases in the northeastern United States over the 10-year period between June 1, 1997 and June 1, 2007. This information was then compared with trends at Cornell University's Equine Hospital during the same time span, which in general agreed with practitioners' opinions. Equine herpes virus-1 (EHV-1) neurologic disease, equine motor neuron disease (EMND), and equine protozoal myelitis (EPM) have historic and current relevance. Results showed that the frequency of EMND and EPM has remained relatively stationary or decreased somewhat, whereas the frequency of the neurologic strain of EHV-1 may have increased slightly over the last decade. Less historical information on clinical disease associated with Borrelia burgdorferi infection (Lyme disease) and Parelaphostrongylus tenuis exists; however, results suggest that P. tenuis in the equine is presently emergent. Opinions regarding the existence and rate of occurrence of clinical borreliosis in horses appear divided. A better understanding of the frequency with which these diseases occur, as well as possible associated positive risk factors, will aid the equine practitioner in making an appropriate diagnosis in cases of neurologic disease in their equine patients.     

Motor neuron abiotrophy in a saluki.

A nine-week-old saluki puppy was presented to Tufts University School of Veterinary Medicine for progressive, generalized weakness and bilateral forelimb deformities. Examination suggested a diffuse neuromuscular lesion. Cerebrospinal fluid (CSF) analysis showed normal nucleated cell count and protein level; however, many macrophages had vacuolated cytoplasm. Electromyography (EMG) recordings suggested denervation in paraspinal and appendicular muscles. Tibial motor nerve conduction velocity was normal, but direct evoked muscle potential had reduced amplitude. Histopathology revealed diffuse, symmetrical, degenerative motor neuronopathy of the ventral horn of the spinal cord with associated lesions in nerves and muscles. Histopathology was consistent with an abiotrophy that was likely inherited.     

Hypoglycemia associated with nonislet cell tumor in 13 dogs

Hypoglycemia associated with nonislet cell tumor was found in 13 dogs. In each dog, clinical signs were related directly to adrenergic and neuroglucopenic effects of hypoglycemia and included collapsing episodes, tremors, restlessness, weakness, and grand mal seizures that were responsive to glucose administration. Eight of the dogs had hepatocellular carcinoma; surgical resection of the tumor achieved remission of clinical signs in 3 of these dogs. Other hepatic tumors associated with hypoglycemia included leiomyosarcoma and hemangiosarcoma involving solitary lobes of the liver. Nonhepatic tumors included splenic hemangiosarcoma, diffuse metastatic melanoma, and salivary gland adenocarcinoma.     

Acquired myasthenia gravis in a cat with thymoma

A 4-year-old castrated Abyssinian cat was evaluated for profound neuromuscular weakness. Results of electromyography and repetitive nerve stimulation tests were normal. Thoracic radiography revealed a cranial mediastinal mass, which was excised and identified as a thymoma. Serum acetylcholine receptor antibodies were detected at high concentration, supporting a diagnosis of acquired myasthenia gravis. Clinical signs of disease responded to treatment with pyridostigmine and corticosteroids.