Search

An 8-year-old neutered male Bengal cat was referred because of a 1-year history of progressive and relapsing generalized muscle weakness and muscle atrophy. Before referral, the cat was treated with immunosuppressive doses of oral prednisolone, intermittently for 6 mo, and had responded well when the immunosuppressive dose was maintained. Generalized paresis, diffuse muscle atrophy, and diminished spinal reflexes were present in all limbs, consistent with a generalized lower motor neuron disease. Histopathologic evaluation of muscle biopsies confirmed a pattern of muscle fiber atrophy consistent with chronic and severe denervation. No specific abnormalities were identified in the nerve biopsy or within intramuscular nerve branches. A presumptive antemortem diagnosis of an adult-onset motor neuron degeneration resembling amyotrophic lateral sclerosis (ALS) or spinal muscle atrophy was suspected. However, given the response to immunosuppressive doses of corticosteroids, an autoimmune process or other degenerative process could not be definitively excluded. Key clinical message: In this case, an adult cat had a chronic, progressive history of lower motor neuron weakness and absent spinal reflexes; biopsies revealed a neurogenic pattern of muscle fiber atrophy and histologically normal peripheral nerve and intramuscular nerve branches. Although reports of motor neuron disease are rare in the veterinary literature, this case report highlights the importance of muscle and nerve biopsies that lead to a presumptive diagnosis of motor neuron degeneration., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Aims: To investigate the pathogenesis of a disease in takahē (Porphyrio hochstetteri) with intracytoplasmic inclusion bodies in lower motor neurons., Methods: Four birds aged between 5 and 12 years, from three different wildlife sanctuaries in New Zealand were examined. Of these, only one had signs of spinal dysfunction in the form of paresis. Stained paraffin sections of tissues were examined by light microscopy and immunostained sections of the ventral horn of the spinal cord by confocal microscopy. Epoxy resin sections of the spinal cord from the bird with spinal dysfunction were examined by electron microscopy., Results: Two types of inclusion bodies were noted, but only in motor neurons of the ventral spinal cord and brain stem. These were large globoid eosinophilic bodies up to 5 µm in diameter, and yellow/brown granular inclusions mostly at the pole of the cell. The globoid bodies stained with Luxol fast blue but not with periodic acid Schiff (PAS), or Sudan black. The granular inclusions stained with Luxol fast blue, PAS and Sudan black. Both bodies were slightly autofluorescent. On electron microscopy the globoid bodies had an even electron-dense texture and were bound by a membrane. Beneath the membrane were large numbers of small intraluminal vesicles. The smaller granular bodies were more heterogeneous, irregularly rounded and membrane-bound accumulations of granular electron-dense material, often with electron-lucent vacuoles. Others were more vesicular but contained varying amounts of electron-dense material. The large globoid bodies did not immunostain for lysosomal markers lysosomal associated protein 1 (LAMP1) or cathepsin D, so were not lysosomal. The small granular bodies stained for cathepsin D by a chromogenic method.A kindred matrix analysis showed two cases to be as closely related as first cousins, and another case was almost as closely related to one of them, but the fourth bird was unrelated to any other., Conclusions: It was concluded that this was an endoplasmic reticulum storage disease due to a specific protein misfolding within endoplasmic reticulum. It was rationalised that the two types of inclusions reflected the same aetiology, but that misfolded protein in the smaller granular bodies had entered the lysosomal system via endoplasmic reticulum autophagy. Although the cause was unclear, it most likely had a genetic aetiology or predisposition and, as such, has clinical relevance.

Neurofilaments (NFs) are structural proteins of neurons that are released in significant quantities in the cerebrospinal fluid and blood as a result of neuronal degeneration or axonal damage. Therefore, NFs have potential as biomarkers for neurologic disorders. Neural degeneration increases with age and has the potential to confound the utility of NFs as biomarkers in the diagnosis of neurologic disorders. We investigated this relationship in horses with and without neurological diagnosis. While controlling for horse type (draft, pleasure, and racing), we evaluated the relationship between serum heavy-chain phosphorylated neurofilaments (pNF-H) and age, sex, and serum vitamin E concentrations. Serum pNF-H concentrations increased by 0.002 ng/ml for each year increase in age. There were significant differences in the serum pNF-H concentration among the type of activity performed by the horse. The highest serum pNF-H concentration was found in horses performing heavy work activity (racehorse) and with lower serum pNF-H concentration found among light (pleasure riding) and moderate (draft) activity. There was no significant association between the pNF-H concentration and sex or vitamin E concentration. Serum pNF-H concentration was elevated among horses afflicted with EMND and EPM when compared with control horses without evidence of neurologic disorders. Accordingly, serum pNF-H concentration can serve as a useful biomarker to complement the existing diagnostic work-up of horses suspected of having EPM or EMND., (Copyright © 2019. Published by Elsevier Ltd.)

We carried out an investigation to identify the factors that predispose to the risk of equine motor neuron disease (EMND) and evaluated the long-term impact of an intervention. Data on several biomarkers, including antioxidants (α-tocopherols, β-carotenes, glutathione peroxidase (GSHPx)), and superoxide dismutase (SOD1), neurofilaments, and other putative risk factors hypothesized to associate with the likelihood of EMND were collected. The data were analyzed for their significance of association with the condition. The EMND outbreak started in 1991 and continued until 1998. A total of 69 EMND cases and 64 control horses met the inclusion criteria and were enrolled in the study. Most cases (74%) occurred in 1996 and 1997. Horses afflicted with EMND had significantly lower plasma levels of vitamin E than control horses (0.381 vs. 1.148 μg/mL). There were no significant differences in the levels of vitamin A, β-carotenes, GSHPx, or the activities of SOD1 between EMND cases and control horses. Horses afflicted with EMND had significantly higher serum levels of phosphorylated neurofilament heavy than controls (2.85 vs. 0.27 ng/mL). The probability of EMND diagnosis increased above 50% when the serum levels of phosphorylated neurofilament heavy increased beyond 2.54 ng/mL. Mixed and Brazilian breeds had a significantly higher risk of EMND in comparison to Standardbred horse among the study population. In 1997, there was a change in the diet where better quality green hay was used. The incidence of EMND dropped to 0 in 1 year after intervention and remained at that level for the past 20 years., (Copyright © 2019. Published by Elsevier Inc.)

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-TP deficiency. The objective of this report is to describe, for the first time, a pigment retinopathy in a family of α-TP-deficient Warmbloods (WB) with clinically apparent NAD/EDM or EMND., Animals and Procedures: Twenty-five WB horses from one farm underwent complete neurologic and ophthalmic examinations and serum α-TP concentrations were assessed. Two of the most severely ataxic horses were euthanized and postmortem examinations performed., Results: Alpha-TP deficiency was widespread on this farm (22 of 25 horses). Eleven of 25 horses were clinically normal (age range 2-12 years), one had signs of EMND (6 years of age), 10 had signs of ataxia consistent with NAD/EDM (1-10 years), and two of these were postmortem confirmed concurrent NAD/EDM and EMND. A pigment retinopathy characterized by varying amounts of granular dark pigment in the tapetal retina was observed in four clinically apparent NAD/EDM horses (two postmortem confirmed concurrent NAD/EDM and EMND) and one horse with clinical signs of EMND., Conclusions: A pigment retinopathy can be present in young α-TP-deficient Warmblood horses with clinical signs of EMND as well as those with signs of NAD/EDM., (© 2016 American College of Veterinary Ophthalmologists.)

Two horses from Saskatchewan were presented with signs of sweating, muscle fasciculations, weight loss, and generalized weakness. The horses were diagnosed with equine motor neuron disease (EMND), by histological assessment of a spinal accessory nerve or sacrocaudalis dorsalis medialis muscle biopsy. This is the first report of EMND in western Canada.

Background: Equine motor neuron disease (EMND) is a neuromuscular disorder that affects adult horses. Although EMND has been linked to vitamin E deficiency, its etiopathogenesis is poorly understood., Objectives: To describe clinical features, laboratory results, and postmortem findings in a series of young horses with motor neuron disease (MND)., Animals: A herd of 15 young Andalusian horses with weakness, weight loss, muscle atrophy, and muscle fasciculations related to restricted intake of green forage., Methods: A case series is presented in which horses were subjected to a clinical examination and plasma vitamin E measurement. Five severely affected horses were euthanized for detailed postmortem examination. Muscle specimens were taken from the M. sacrocaudalis dorsalis medialis and the M. gluteus medius for histopathologic and morphometric evaluation., Results: MND was diagnosed in 5 horses based on clinical signs, low serum levels of vitamin E (0.11 ± 0.05 mg/dL; normal range,: 0.3-1.5 mg/dL), changes in muscle histopathology (neurogenic atrophy), and spinal cord lesions (neuronal chromatolysis in ventral horns). An unexpected postmortem finding was the presence of intestinal inflammation (catarrhal enteritis, edema, and eosinophilic infiltrate) associated with the presence of giant ciliated protozoa in all of the horses., Conclusions: Although a mechanistic link could not be established, it is hypothesized that intestinal inflammation may have been involved in the decreased absorption of vitamin E, thus favoring the development of MND., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: An astrocyte-associated motor neurone syndrome was produced in molybdenum-deprived sheep fed xanthosine. Mo-deprived sheep fed inosine, adenosine or guanosine would be also expected to develop astrocyte-associated motor neurone syndromes, because all these purine nucleosides can act as neuromodulators and all depend on the Mo-associated enzyme xanthine oxidase-dehydrogenase for their catabolism., Design: To investigate the relationship between inosine ingestion and low Mo concentration, eight sheep were fed lucerne chaff with a Mo value <0.10 ppm and the Mo antagonist, sodium tungstate, for 21 weeks, with inosine (35 mg/kg/day) fed for the last 18 of these weeks. This clinical study was uncontrolled., Results: An astrocyte-associated motor neurone syndrome was produced in three sheep 18-27 months later. It was characterised by diaphragmatic, laryngeal, lingual and pharyngeal muscle weakness. The diaphragmatic muscle weakness was the most severe and potentially lethal., Conclusion: These findings suggest that purinergic neuromodulation of respiration, vocalisation and swallowing is different to that of limb movement. The syndrome produced, and assumed to be caused by the treatment given, has not been reported in livestock. A similar syndrome is seen in human motor neurone disease, but not in equine motor neurone disease, and this is consistent with it being an upper, not a lower, motor neurone effect., (© 2015 Australian Veterinary Association.)

While toxins from aquatic cyanobacteria are a well-recognised cause of disease in birds and animals, exposure of grazing livestock to terrestrial cyanobacteria has not been described. This study identified terrestrial cyanobacteria, predominantly Phormidium spp., in the biofilm of plants from most livestock fields investigated. Lower numbers of other cyanobacteria, microalgae and fungi were present on many plants. Cyanobacterial 16S rDNA, predominantly from Phormidium spp., was detected in all samples tested, including 6 plant washings, 1 soil sample and ileal contents from 2 grazing horses. Further work was performed to test the hypothesis that ingestion of cyanotoxins contributes to the pathogenesis of some currently unexplained diseases of grazing horses, including equine grass sickness (EGS), equine motor neuron disease (EMND) and hepatopathy. Phormidium population density was significantly higher on EGS fields than on control fields. The cyanobacterial neurotoxic amino acid 2,4-diaminobutyric acid (DAB) was detected in plant washings from EGS fields, but worst case scenario estimations suggested the dose would be insufficient to cause disease. Neither DAB nor the cyanobacterial neurotoxins β-N-methylamino-L-alanine and N-(2-aminoethyl) glycine were detected in neural tissue from 6 EGS horses, 2 EMND horses and 7 control horses. Phormidium was present in low numbers on plants where horses had unexplained hepatopathy. This study did not yield evidence linking known cyanotoxins with disease in grazing horses. However, further study is warranted to identify and quantify toxins produced by cyanobacteria on livestock fields, and determine whether, under appropriate conditions, known or unknown cyanotoxins contribute to currently unexplained diseases in grazing livestock.

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.

Objective: To investigate the influence of oxidative stress in terms of antioxidant capacity and lipid peroxidation on the probability of motor neuron disease (MND) in horses., Animals: 88 horses with MND (cases) and 49 controls., Procedures: Blood samples were collected from all horses enrolled, and RBCs and plasma were harvested. Activity of the enzyme erythrocytic superoxide dismutase 1 (SOD1) was determined in the RBCs. Plasma concentrations of α-tocopherols and β-carotenes and activity of glutathione peroxidase were also evaluated. Degree of lipid peroxidation was measured by determining plasma concentrations of lipid hydroperoxides. Differences were evaluated between horse groups., Results: Cases had lower erythrocyte SOD1 activity than did controls, but the difference was not significant. On the other hand, plasma vitamin E concentrations differed significantly between groups, with the cases having lower concentrations. Neither plasma vitamin A concentration nor glutathione peroxidase activity differed between groups; however, cases had significantly higher concentrations of lipid hydroperoxides (18.53μM) than did controls (12.35μM)., Conclusions and Clinical Relevance: Horses with MND differed from those without MND by having a lower plasma concentration of vitamin E and higher concentrations of lipid hydroperoxides. Results parallel the findings in humans with sporadic amyotrophic sclerosis and provide evidence supporting the involvement of oxidative stress in the 2 conditions.

A central nervous disorder occurred spontaneously in a herd of feeder pigs characterized by muscle fasciculations, convulsions, squealing, and acute death in numerous animals. Histopathology revealed a degenerative poliomyeloencephalopathy of brain stem and spinal cord consisting of neuronal hypertrophy, chromatolysis, neuronophagia, and satellitosis associated with Wallerian degeneration of ventral rootlets and neurogenic muscle atrophy of limb musculature. The sudden onset of clinical signs and the pattern of morphological findings were suggestive of intoxication. Though parathion was found in two animals, serum acetylcholine esterase activity and morphological findings were not compatible with an organophosphate poisoning. A hereditary disorder was excluded by genetic analysis. Summarized findings in the present cases are reminiscent of changes observed in ruminants suffering from patulin poisoning, a neuromycotoxicosis caused by Aspergillus clavatus. However, toxicological and microbiological investigations failed to identify the cause of this unusual and so far not described disease in pigs. Morphologically, lesion distribution and alterations of motor neurons resemble changes observed in equine motor neuron disease, spinal muscular atrophy of certain canine breeds, and amyotrophic lateral sclerosis (Lou Gehrig's disease) in man. Therefore, the term spontaneous porcine motor neuron disease (SPMND) is proposed for this new and unique entitiy.

A type of lower motor neuron (LMN) disease inherited as autosomal recessive in Romney sheep was characterized with normal appearance at birth, but with progressive weakness and tetraparesis after the first week of life. Here, we carried out genome-wide homozygosity mapping using Illumina Ovine SNP50 BeadChips on lambs descended from one carrier ram, including 19 sheep diagnosed as affected and 11 of their parents that were therefore known carriers. A homozygous region of 136 consecutive single-nucleotide polymorphism (SNP) loci on chromosome 2 was common to all affected sheep and it was the basis for searching for the positional candidate genes. Other homozygous regions shared by all affected sheep spanned eight or fewer SNP loci. The 136-SNP region contained the sheep ATP/GTP-binding protein 1 (AGTPBP1) gene. Mutations in this gene have been shown to be related to Purkinje cell degeneration (pcd) phenotypes including ataxia in mice. One missense mutation c.2909G>C on exon 21 of AGTPBP1 was discovered, which induces an Arg to Pro substitution (p.Arg970Pro) at amino-acid 970, a conserved residue for the catalytic activity of AGTPBP1. Genotyping of this mutation showed 100% concordant rate with the recessive pattern of inheritance in affected, carrier, phenotypically normal and unrelated normal individuals. This is the first report showing a mutant AGTPBP1 is associated with a LMN disease in a large mammal animal model. Our finding raises the possibility of human patients with the same etiology caused by this gene or other genes in the same pathway of neuronal development.

Background: The occurrence of Tribulus terrestris motor neurone disease (MND) in sheep is linked with grazing Tribulus growing on cultivation paddocks. A previous survey found that the molybdenum (Mo) content of Tribulus growing on uncultivated soils in the Coonabarabran district of New South Wales was 3.03 ppm, but on cultivated soils it was <0.04 ppm. Tribulus contains the purine, xanthosine, which functions as a neuromodulator, and the catabolism of xanthosine is Mo-dependent., Design: To investigate the relationship between xanthosine ingestion and low Mo concentration, eight sheep were fed Mo-deficient lucerne chaff (<0.10 ppm), the Mo antagonist, sodium tungstate, and xanthosine (25 mg/kg/day) over 18 weeks and then returned to pasture., Results: Signs of MND developed in two sheep 30 months later and astrocyte degeneration occurred in all sheep., Conclusion: The findings were similar to those observed in sheep with T. terrestris MND, suggesting that the combination of xanthosine ingestion and Mo deficiency may be the cause of this disorder., (© 2012 The Author. Australian Veterinary Journal © 2012 Australian Veterinary Association.)

Objective: To describe the application of intermittent positive pressure ventilation (IIPV) in dogs with lower motor neuron disease (LMND)., Design: Multi-institutional, retrospective study (2003-2009)., Setting: Intensive care units at multiple university teaching hospitals., Animals: Fourteen dogs with LMND that underwent IIPV., Interventions: None., Measurements and Main Results: The ventilatory logs of 4 teaching hospitals were searched for dogs undergoing IIPV in association with a diagnosis of acute LMND. The medical records were evaluated for signalment, specific LMND, ventilatory management and duration, complications associated with ventilation, duration of hospitalization, and outcome. Descriptive statistics were used as indicated. Fifteen records were evaluated, 1 dog was excluded since it experienced cardiopulmonary arrest (CPA) before commencement of IIPV. The median age was 7.0 years (range 10 mo to 12 y). There were 5 Labrador retrievers, 4 mixed breeds, and 5 other breeds were each represented once. Five dogs were diagnosed with myasthenia gravis, 4 dogs with polyradiculoneuritis, and 5 dogs had an undetermined LMND. Clinical signs of weakness before ventilation were present for a median of 36 hours (range 6 h to 14 d). Dogs were ventilated for a median of 109 hours (range 5-261 h). Nine dogs had temporary tracheostomies performed, and 8 dogs received nutritional support. Five dogs developed ventilator associated pneumonia. Six dogs were successfully weaned from the ventilator with a median ventilatory time of 49 hours (range 25-192 h). Three dogs survived to discharge. No single LMND was associated with a better outcome., Conclusions: High euthanasia rates and iatrogenic complications limit the ability to accurately prognosticate for affected dogs in this retrospective study, but in dogs with LMND that is severe enough to require IIPV, support may be required days to weeks., (© Veterinary Emergency and Critical Care Society 2011.)

Case Description: A 23-year-old female mule was presented for bilateral ocular abnormalities and an abnormal pelvic limb gait., Clinical Findings: Anisocoria, unilateral enophthalmos, medial strabismus, ptosis, pupillary light reflex deficits, and bilateral reticulated pigmentary retinopathy were observed on ophthalmic examination. Neurologic abnormalities included right-sided facial nerve paralysis, extensive symmetric muscle atrophy, and asymmetric pelvic limb ataxia with an abnormal pelvic limb gait. A positive titer (1:40) for equine protozoal myeloencephalitis (EPM) associated with Neospora hughesi was obtained from cerebrospinal fluid with minimal (<1 red blood cell/microL) blood contamination. Muscle biopsies of the sacrocaudalis dorsalis medialis muscle revealed predominantly type I neurogenic muscle atrophy, consistent with a diagnosis of equine motor neuron disease (EMND)., Treatment and Outcome: Treatment included a 2-month course of ponazuril (5 mg/kg PO q24 h), vitamin E (8000 IU PO q24 h), and selenium (2 mg PO q24 h). Clinical improvement was not observed after 2 months although the mule remained stable. Clinical deterioration was reported upon discontinuation of the ponazuril after a 2-month course., Conclusion: Concurrent disease with EPM associated with N. hughesi and EMND should be considered in cases demonstrating cranial nerve abnormalities, pronounced symmetric muscle atrophy, unusual asymmetric gait abnormalities, and reticulated pigmentary retinopathy.

Practical Relevance: Weakness is recognized somewhat infrequently in cats, but is an important manifestation of neurological disease. The clinician must perform a complete neurological examination to determine the neuroanatomic basis for the weakness. As for all species, the neuroanatomic diagnosis allows the clinician to generate an appropriate differential diagnosis, to design a diagnostic plan, to prognosticate, and ultimately to develop a treatment plan., Clinical Challenges: The cause(s) of neurological weakness in the cat may be difficult to determine without access to advanced imaging modalities, cerebrospinal fluid analysis or electrodiagnostics. However, an accurate neuroanatomic diagnosis allows the clinician to pursue preliminary anomalous (vertebral anomalies), metabolic (eg, diabetes mellitus, electrolyte abnormalities) and neoplastic differentials via blood work, vertebral column and thoracic radiography, and abdominal ultrasound. Subsequently, referral to a specialty veterinary hospital may be warranted to pursue advanced neurodiagnostics., Audience: This review provides a framework for generating a neuroanatomic and differential diagnosis in the weak cat. It also discusses the pathogenesis and clinical signs associated with the most common neurological differentials for feline paresis. As such, it is aimed at both primary health care and specialty veterinarians., Patient Group: The neurological conditions discussed in this review cause weakness in cats of all age groups.

The antioxidant status of 10 horses living in stable 1 where 2 cases of equine motor neuron disease had previously been diagnosed was assessed before and 9 weeks after moving to another stable. Duration of residence in stable 1, subsequent moving, or both, significantly affected several parameters of the antioxidant status.

Background: Equine motor neuron disease (EMND) is a spontaneous neurologic disorder of adult horses which results from the degeneration of motor neurons in the spinal cord and brain stem. Clinical manifestations, pathological findings, and epidemiologic attributes resemble those of human motor neuron disease (MND). As in MND the etiology of the disease is not known. We evaluated the predisposition role of vitamin E deficiency on the risk of EMND., Methods: Eleven horses at risk of EMND were identified and enrolled in a field trial at different times. The horses were maintained on a diet deficient in vitamin E and monitored periodically for levels of antioxidants--alpha-tocopherols, vitamins A, C, beta-carotene, glutathione peroxidase (GSH-Px), and erythrocytic superoxide dismutase (SOD1). In addition to the self-control another parallel control group was included. Survival analysis was used to assess the probability of developing EMND past a specific period of time., Results: There was large variability in the levels of vitamins A and C, beta-carotene, GSH-Px, and SOD1. Plasma vitamin E levels dropped significantly over time. Ten horses developed EMND within 44 months of enrollment. The median time to develop EMND was 38.5 months. None of the controls developed EMND., Conclusion: The study elucidated the role of vitamin E deficiency on the risk of EMND. Reproducing this disease in a natural animal model for the first time will enable us to carry out studies to test specific hypotheses regarding the mechanism by which the disease occurs.

Oxidative stress refers to the cellular injury and pathologic change that occurs when there is an imbalance favoring oxidants over antioxidants within a living organism. In human medicine, oxidative stress has been implicated in numerous disease processes, which has led to further research into the clinical benefits and efficacy of antioxidant therapy. The evaluation of oxidative stress in the horse has been limited primarily to ischemia-reperfusion injury of the gastrointestinal tract, recurrent airway obstruction, exercise, osteoarthritis, equine motor neuron disease, and pituitary pars intermedia dysfunction. Each of these is examined in this review in terms of the current evidence for oxidative stress as well as the evidence for current antioxidant therapy in equine medicine and the potential of future research and therapies. Oxidative stress research is currently an emerging field with relevance to the equine critical patient.

We report a case of EMND in a heavy horse that was bred and trained in Hokkaido, Japan. Clinical symptoms included severe ataxia of all four limbs, tilted head, lethargy, and flaccid lips. Numerous axonal degenerations and swellings were observed in nuclei, mostly in the cerebellar dentate nucleus and the nucleus of the hypoglossal nerve, and in the ventral horn of the spinal cord. In the ventral horn of the spinal cord, neuronal degeneration, swelling, and/or necrosis were observed sporadically. The case was diagnosed as EMND from the clinical symptoms and pathological findings.

Neurodegenerative diseases are characterised by selective damage to specific neurons in the nervous system. Interest in such diseases in humans has resulted in considerable progress in the molecular understanding of these disorders in recent decades. Numerous neurodegenerative diseases have also been described in domestic animals but relatively little molecular work has been reported. In the present review, we have classified neurodegenerative disease according to neuroanatomical criteria. We have established two large groups, based on whether the neuronal cell body or its axon was primarily affected. Conditions such as motor neuron diseases, cerebellar degenerations and neuroaxonal dystrophies are discussed in terms of their clinical and neuropathological features. In the most studied disorders, we also present what is known about underlying pathomechanisms, and compare them with their human counterparts. The purpose of this review is to re-kindle interest in this group of diseases and to encourage veterinary researchers to investigate molecular mechanisms by taking advantage of current diagnostic tools.

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.

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.

Objective: To observe the clinical signs of sheep affected by Tribulus terrestris motor neuron disease, to ascertain their response to striatal dopamine reducing drugs, and to examine their brains and spinal cords for microscopic changes., Procedures: Twenty-eight sheep displaying well developed clinical signs of the disorder were observed. Twenty-two of these and 22 normal sheep were then randomly allocated to three groups and treated with diazepam, chlorpromazine, or xylazine. The time that it took an animal to return to a standing position following drug administration was recorded. The brain and complete spinal cord were removed from each of the other six affected sheep and fixed in formalin. Brains were sectioned throughout at 5 mm intervals and spinal cords at 10 mm intervals. All tissues were paraffin embedded and examined by light microscopy. A few samples were examined by electron microscopy., Results: Clinical signs included postural asymmetry with a right:left body-side dominance within the group of 50:50, unequal flaccid paresis in the pelvic limbs, extensor muscle atrophy and adduction of the weaker pelvic limb, and concurrent abduction of the stronger. Forward motion followed either a fixed left or right hand curved trajectory, the sheep no longer being able to choose which. Twelve animals intermittently displayed rotational behaviour that involved loss of postural balance without locomotor activation. The administration of diazepam, chlorpromazine, or xylazine caused limb paresis and sedation, with affected sheep being slower than normal sheep by factors of 8, 3 and 2 respectively, to return to a standing position. There were scattered areas of mild Wallerian degeneration throughout the spinal cord, and in both the brain and the cord there were small numbers of degenerate astrocytes containing novel cytoplasmic pigment granules., Conclusions: Affected sheep had a dysfunction in the control of directional change and this provides a new insight into the normal mechanism for 'turning' in quadrupeds. Directional change requires a functional asymmetry or lateralisation within the upper motor neuron to accommodate a difference in the rate of forward progression of each body side and, simultaneously, a lateral shift of the centre of gravity. The sensitivity of affected sheep to diazepam is consistent with a pre-existing elevation in GABAergic neuronal inhibition, probably as a result of a reduction in glutamatergic neuronal excitation. The cytoplasmic pigment found in degenerate astrocytes was novel and its presence in the brain nuclei known to contribute to turning behaviour could have aetiological significance. The motor output of the basal ganglia in Tribulus neurotoxicity appeared to be excessively inhibitory to the pelvic limb extensor muscles and was asymmetric, causing fixation of the turning posture but not locomotor activation. An intoxication of specific purine sensitive, glutamate releasing astrocytes, located in nuclei controlling turning, was suspected.

This study was carried out to investigate the motor neurone degeneration in the ventral horn following transient spinal cord ischaemia at normothermic conditions in rabbits. Transient spinal cord ischaemia was induced by occlusion of the abdominal aorta underneath the left renal artery for 15 min at normothermia (38.7 degrees C). Sections at the level of L7 were examined using histochemical and electron microscopic methods. Cresyl violet-positive motor neurones began to reduce in number at 3 h after ischaemia reperfusion, and were not detectable at 48 h after ischaemia reperfusion. Acid fuchsin-positive motor neurones were detected at 1 h after ischaemia reperfusion, significantly increased up to 6 h after the ischaemia reperfusion, and eventually disappeared by 48 h after ischaemia reperfusion. In electron microscopic findings, the disintegration of cytoplasmic membranes, and the disruption of mitochondria and endoplasmic reticulum were observed in motor neurones at 30 min after ischaemia reperfusion. Motor neurones showed necrotic findings with pyknotic degeneration at 1 h after ischaemia reperfusion. The necrotic degeneration became severer time dependently after ischaemia reperfusion. At 48 h after ischaemia reperfusion, cellular components were not detectable in motor neurones. In conclusion, we suggest that the degeneration pattern of motor neurones of the ischaemic spinal cord was necrotic after ischaemia reperfusion under normothermic conditions.

Equine motor neuron disease (EMND) is a neurodegenerative disorder similar to the sporadic form of human amyotrophic lateral sclerosis. This study was conducted to quantify myofiber plasticity in response to EMND. Deep M. gluteus medius biopsy samples from eight horses with an ante mortem diagnosis of EMND, which in five cases was later confirmed by post mortem examination of spinal cord and peripheral nerves, were examined by combined methodologies of electrophoresis of myosin heavy chains (MyHC), muscle enzymes and substrate biochemistry, immunohistochemistry of MyHCs and sarcoendoplasmic Ca2+-ATPase (SERCA) isoforms, quantitative histochemistry of succinic dehydrogenase, glycerol-3-phosphate dehydrogenase, periodic acid-Schiff and capillaries, and photometric image analysis. The data were compared with muscle biopsies from healthy controls. Histopathological findings of EMND were observed in muscle biopsy specimens from all cases, but the severity and intra-biopsy extent varied from case to case. Compared with controls, muscle biopsy samples from EMND horses had a lower percentage of MyHC type I fibers, higher percentages of hybrid IIAX and pure IIX fibers, significant atrophy of all muscle fiber types, reduced oxidative capacity, increased glycolytic capacity, diminished intramuscular glycogen, lower capillary-to-fiber ratio, a higher ratio of myofibers expressing SERCA1a to SERCA2a isoforms, and a lower percentage of fibers expressing phospholamban. Objective discrimination of muscle biopsy specimens according to their healthy status (EMND vs controls) was possible on the basis of their muscular characteristics. A coordinated shift from slow to fast muscle characteristics in contractile and metabolic features of muscle fiber types, together with generalized myofiber atrophy, occurs in EMND and the extent of this change seems to be related to the duration of the disease.

Objectives: To determine whether increased glucose metabolism is the potential cause of the decreased plasma glucose curve determined after oral glucose tolerance testing in horses with lower motor neuron degeneration., Animals: 3 horses with signs suggestive of lower motor neuron degeneration, 1 horse with malignant melanoma with multiple metastases, and an obese but otherwise healthy horse. Procedures-Glucose metabolism was assessed by use of the hyperglycemic clamp and euglycemic hyperinsulinemic clamp techniques., Results: Mean rate of glucose metabolism of horses with lower motor neuron degeneration was significantly greater (mean, 3.7 times greater than control horses; range, 2.1 to 4.8 times greater) than that reported in 5 healthy control horses (41 +/- 13 micromol/kg/min vs 11 +/- 4.5 micromol/kg/min, respectively). In addition, one of the affected horses, an 8-year-old warmblood gelding, had a 5.6-times increased sensitivity to exogenously administered insulin, compared with that reported in 5 healthy control horses. Pancreatic insulin secretion was not insufficient in horses with lower motor neuron degeneration. Findings in the 2 diseased control horses were unremarkable., Conclusions and Clinical Relevance: Increased glucose metabolism in horses with lower motor neuron degeneration may be the cause of the decreased plasma glucose curve detected after oral glucose tolerance testing. This finding could aid in developing supportive treatments with respect to adequate glucose and vitamin E supplementation.

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.

Hereditary canine spinal muscular atrophy is an autosomal dominant version of motor neuron disease in which motor units exhibit extensive dysfunction before motor terminal or axonal degeneration appear. We showed in a previous paper that motor endplate currents (EPCs) are reduced and that failures of nerve-evoked EPCs appear in the homozygote medial gastrocnemius (MG) muscle in which failing motor units are also found, suggesting a presynaptic deficit of ACh release. To examine this further, we performed a detailed analysis of synaptic release properties in the MG muscle of homozygotes and compared the results with data from genetically normal control animals. We found that the amplitude of miniature EPCs (mEPC) did not differ between homozygote and normal synapses, indicating that quantal content is reduced at homozygote motor terminals. Consistent with this, deconvolution analysis showed that the maximum release rates at homozygote motor terminals were significantly reduced relative to normal. This analysis also demonstrated that the time course of quantal release at homozygote synapses did not differ from normal. The extent of quantal release depression during high-frequency activation in homozygotes did not differ from normal despite the significant reduction of quantal content and maximum release rate. Surprisingly, the absolute amount of posttetanic potentiation was not decreased at homozygotes motor terminals despite the differences in quantal content. We conclude that failure of homozygote motor unit force during repetitive activity is due to a unique combination of low quantal content and normal release depression and suggest that the primary deficit in homozygote motor terminals is a reduced supply of readily releasable quanta.

Equine grass sickness (EGS) is an acquired disease of unknown aetiology affecting horses kept at grass. The disease is characterised by postganglionic sympathetic and parasympathetic neuronal pathology and is categorised as a dysautonomia. This study undertook a systematic examination of brain stem cranial nerve nuclei in 59 cases of EGS. Pathology consisting of neuronal chromatolysis was most consistently noted in the lower motor neurons of the general visceral efferent nucleus of CN III and X and the general somatic efferent nuclei of CN III, V, VII and XII. The prevalence of chromatolysis differed significantly between the diagnostic categories and was inversely related to the age of the animal. Duration of disease had a small but significant negative effect on the proportion of nuclei with chromatolytic neurons in chronic cases. The distribution of chromatolytic neurons is unlike that reported in any other equine or human disease; however, it appears to be equivalent to that in other animals with primary dysautonomias. EGS should be classified as a multisystem disease.

A 10-year-old, non-pregnant Dutch Warmblood mare was referred to the Department of Equine Science because of chronic weight loss, despite good appetite, and dullness. Clinical examination revealed muscle atrophy, trembling of the limb muscles, an abnormal stance in which all four limbs were placed under the body, and an abnormal low head carriage. The plasma vitamin E concentration was markedly decreased (0.2 mumol/l), the electromyographic (EMG) examination was consistent with denervation, and the oral glucose absorption test was below the reference value (40% increase over the resting glucose level). Because of the clinical diagnosis of equine motor neuron disease (EMND), the horse was euthanazed and post-mortem examination confirmed this diagnosis. Based on the similarity in pathological findings, EMND can be compared to amyotrophic lateral sclerosis (ALS) in humans. However, in horses, only the lower motor neurons and occasionally some nuclei of the cranial nerves are affected. Because of the low plasma vitamin E concentration found in horses with EMND, an absolute or a relative antioxidant deficiency can be involved in the pathogenesis. In general, it is a progressive disease process and stabilization of the situation is the best feasible result. There is no specific therapy other than vitamin E supplementation and the prognosis is poor.

Electromyography was used as an aid to the diagnosis of equine motor neuron disease in a conscious horse while it was under caudal epidural anaesthesia. A muscle biopsy was taken to confirm the diagnosis which was then supported by a postmortem examination.

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.

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.

A male 14-year-old Arab horse was pathologically diagnosed as equine motor neuron disease (EMND), which was kept as a breeding horse on a farm in Tokachi district of Hokkaido in Japan. On examination of the peripheral nerves, the most characteristic feature was Wallerian-type degeneration revealed by myelinoclasis associated with myelin ovoids which were sometimes infiltrated by macrophages. The other abnormalities were axonal swellings which were surrounded by thin myelin sheaths. Ultrastructurally, the axonal swelling was due to an accumulation of neurofilaments, and was accompanied by a thin and degenerating myelin sheaths. In teased nerve fiber preparations, the most conspicuous change was myelinoclasis represented by segmentation into myelin ovoids or balls. Occasionally, segmental demyelination and axonal degeneration characterized by multifocal axonal swelling were observed.

Clinical, electromyographic, and pathologic findings characteristic of lead toxicosis were detected in a turkey vulture (Cathartes aura). The bird had generalized lower motor neuron dysfunction that progressed over 5 days. Electromyography revealed diffuse denervation potentials and a presumed decrement in the sciatic-tibial nerve conduction velocity. Histologic examination of peripheral nerves obtained at necropsy revealed changes that could be compatible with lead-induced neuropathy. Lead toxicosis was confirmed by determination of blood lead concentrations. Lead toxicosis causing neurologic disorders in birds has been described. However, this report emphasizes the effects of lead on the peripheral nervous system and demonstrates the use of electromyography for diagnosis of peripheral neuropathy in birds.

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.

Two 2-month-old Griffon Briquet Vendéen pups from the same litter were evaluated for progressive weakness and hind limb paresis. The paraparesis progressed rapidly to extensor paralysis with subsequent involvement of the forelimbs with flexor paralysis. The appendicular muscles of all four limbs became progressively atrophied. Lesions included severe loss of neurons in the ventral horns of the spinal cord, Wallerian degeneration of ventral spinal roots, and peripheral nerve and neurogenic appendicular muscular atrophy. The clinical and morphological findings were consistent with a progressive lower motor neuron disease.

The mean number of motor neurons was assessed in the C7 spinal cord segment of 5 EMND and 5 control horses. Mean number per section in EMND horses was reduced significantly (P<0.001). The mean neuronal loss was estimated at 31%. Each of the 5 affected horses had a mean neuronal count below the 95% confidence interval for control horses. The statistically significant difference between the 2 groups was consistent in the cranial, middle and caudal thirds of the C7 segment (P<0.001). The results of regression analysis indicated an association between neuronal reduction in EMND horses and the duration of the disease when adjusted for age (P<0.001). This is the first quantitation of the neurodegenerative loss in EMND and it provides a clearer explanation for residual deficits in horses that survive EMND.

Motor neuron diseases of domestic animals have rarely been described. Three cats with adult-onset, chronic, progressive generalized muscle weakness characterized initially by trembling on exertion and later by extreme difficulty in walking, cervical ventroflexion, dysphagia, and marked muscle atrophy were elevated. Spinal reflexes were evident early but were nondetectable as the disease progressed. Electromyography revealed fibrillation potentials, with nerve conduction velocities within the reference range. Histologic examination of muscle specimens revealed denervation. Marked neuron loss and gliosis were detected in the ventral horns of the spinal cord, with atrophy of ventral nerve rootlets. Less dramatic neuron loss was seen in brain stem motor nuclei. Electron microscopic examination of the ventral horns disclosed hypertrophied astrocytes, with densely arrayed intermediate filaments, swollen axons with large filamentous accumulations, and many macrophages with lipofuscin-like inclusions. Clinical and pathologic findings were consistent with a progressive neurodegenerative disease affecting spinal and some bulbar motor nuclei.

Objective: To identify intrinsic, management, nutritional, and environmental risk factors associated with equine motor neuron disease (EMND) and to determine whether epidemiologic evidence supports oxidative stress as a risk factor for developing EMND., Design: Case-control study., Animals: 87 horses with EMND and 259 control horses., Procedure: Information concerning each horse's history of exposure to multiple environmental factors prior to developing EMND was obtained by means of a questionnaire or personal interview. Exposure histories of horses with EMND and control horses were compared, and the association of each risk factor with EMND was evaluated, using logistic regression analysis., Results: Factors significantly associated with risk of developing EMND included age, breed of horse, duration of residence at the farm, not vaccinating against rabies, and certain feeding practices. Horses that were exercised on green pasture or in grass paddocks were less likely to develop EMND, compared with horses that were exercised in dirt pad-docks. Feeding complete pelleted feed as the only source of concentrate or combined with sweet feed was associated with a significant increase in the risk of EMND. Supplementary feeding of vitamin and mineral mixtures not formulated to provide vitamin E or selenium was associated with increased risk of EMND. Horses with a history of cribbing or coprophagia were also at higher risk of developing EMND., Clinical Implications: Several husbandry practices and intrinsic characteristics of horses appear to modify the risk of EMND. The relationship of specific nutritional factors to EMND supports the hypothesis that a deficiency of vitamin E contributes to the disease.