A case of equine motor neuron disease (EMND)

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.     

Idiopathic acute onset myelopathy in cheetah (Acinonyx jubatus) cubs.

Numerous cases of ataxia, hind limb paresis, and paralysis have occurred in cheetah (Acinonyx jubatus) cubs over the past 10 yr within the European Endangered Species Program population, including 12 in mainland Europe, two in the British Isles, one in Namibia, and one in Dubai. The condition is the most important medical factor limiting European cheetah population growth. Eight cubs at the Salzburg Zoo, Austria, were affected. They demonstrated upper motor neuron lesions when alive and bilateral, symmetrical myelin degeneration of the spinal cord on necropsy. Ballooning of myelin sheaths surrounded mostly preserved axons, and no spheroids, characteristic of acute axonal degeneration, were found. Myelin loss markedly exceeded axonal degeneration. The syndrome's etiology is unclear, although viral, bacterial, parasitic, genetic, nutritional-metabolic, toxic, and physical causes have been considered.     

Multisystem Neuronal Degeneration in Cocker Spaniels

Four young Cocker Spaniels had slowly progressive neurologic signs with ataxia and mental deterioration. Pathologically, the lesions consisted of diffuse nerve cell loss, gliosis, axonal degeneration, and some demyelination in several areas of the brain. Pedigree analysis strongly suggests a hereditary cause for this disease, which is classified as a multisystem neuronal degeneration. This disorder has not been previously reported and has some resemblance to certain degenerative neurologic diseases found in humans. The clinical differential diagnosis includes cerebellar degeneration and lysosomal storage diseases. A definitive diagnosis requires postmortem examination.     

Progressive encephalomyelopathy and cerebellar degeneration in 10 captive-bred cheetahs

Progressive ataxia, with head tremor, developed in 10 captive-born cheetah cubs under six months of age. The condition was usually preceded by coryza and an ocular discharge. Initially the ataxia and weakness affected the hindquarters, then the forelegs, and head tremor developed later. Significant pathological changes were confined to the central nervous system. There was widespread Wallerian degeneration in the funiculi of the spinal cord (except those in the dorsal columns), in the medulla and in the cerebellum. In the cerebellum there was degeneration of Purkinje cells and of the molecular and granular cell layers. There was chromatolysis in the Purkinje cells, the ventral horn cells of the spinal cord and in the neurons of the lateral vestibular nucleus. The olivary nucleus was necrotic. There were foci of inflammatory cells in the molecular layer of the cerebellum and in the medulla. The cause of the disease remains unknown.     

A degenerative myelopathy in young German shepherd dogs

Two young male German shepherd dogs, six and seven months old, were evaluated for progressive hindlimb ataxia and paresis. Both dogs were found to be thin and poorly muscled on physical examination, and on neurological examination, the lesions were localised to the spinal cord between T2 and L4. Microscopical examination of the spinal cords demonstrated widespread axonal degeneration similar to that seen in aged German shepherd dogs with chronic degenerative radiculomyelopathy (CDRM), although the distribution of these changes was not identical to CDRM.     

Cerebellar degeneration in cattle grazing Solanum bonariense ("Naranjillo") in Western Uruguay.

Cattle in western Uruguay that were eating Solanum bonariense developed periodic episodes of ataxia, hypermetria, hyperesthesia, head and thoracic limb extension, opisthotonus, nystagmus, and falling to the side or backward. Similar clinical signs were experimentally reproduced in cattle by administration of S. bonariense via rumen cannula at a dose of 1,024 g/kg body mass. No significant gross lesions were observed in field cases or experimentally induced cases. Spontaneous and induced histologic lesions were similar and included vacuolation, degeneration, and loss of Purkinje cells. Axonal spheroids, microcavitations, and other changes of wallerian-type degeneration in cerebellar white matter were also observed. Ultrastructural changes included increased number of electron-dense residual storage bodies in membrane-bound vesicles in affected Purkinje cells, and similar vesicles and mitochondria in axonal spheroids. No histologic lesions were detected in the other examined tissues. The Purkinje-cell swelling and vacuolation with subsequent cerebellar degeneration are suggestive of Purkinje-cell specific toxin that produces abnormal lysosome function and cell specific axonal transport. This is the first report of S. bonariense toxicity.     

Peripheral nerve pathology in two rottweilers with neuronal vacuolation and spinocerebellar degeneration

Neuronal vacuolation and spinocerebellar degeneration in young Rottweiler dogs is a neurodegenerative condition characterized by neuronal vacuolation of several nuclei in the central nervous system and degeneration of the spinal cord white matter. Here, we describe the morphologic and ultrastructural findings in laryngeal muscles and peripheral nerves of a 16-week-old female and a 32-week-old female Rottweiler dog affected by progressive ataxia and tetraparesis associated with laryngeal paralysis. Lesions were characterized by neurogenic muscle atrophy of the intrinsic laryngeal muscles, and a loss of large myelinated fibers in the recurrent laryngeal nerve, accompanied by demyelinating/remyelinating features affecting the small myelinated fibers. No significant changes were detected in the cranial laryngeal, vagus, phrenic, ulnar, or peroneal nerves. These findings were indicative of a selective distal neuropathy of the recurrent laryngeal nerve with early severe axonal degeneration, mainly of the large myelinated fibers.     

Neuroaxonal dystrophy in a rottweiler pup

An 8-month-old Rottweiler pup was evaluated for neurologic disorder. Clinical signs included ataxia, hypermetria of all 4 limbs, intention tremors of the head, lack of a menace reflex bilaterally, and mild proprioceptive deficits. The pup was euthanatized because of the progressive nature of the disease. Histopathologic findings consisted of decreased numbers of Purkinje cells in the cerebellum and moderate numbers of axonal spheroids in the nucleus cuneatus. This latter finding confirmed the diagnosis of neuroaxonal dystrophy.     

Cerebellar abiotrophy in crossbred cattle

Cerebellar abiotrophy affected 9 of 74 calves sired by a Poll Hereford bull over 2 successive calving seasons. The disease was characterised by episodes of recumbency and ataxia, with hypermetria and wide base stance. Clinical signs commenced between birth and 8 months of age. Two calves which were affected first at 8 months of age recovered clinically 9 months later. Histological lesions were found in the cerebellar cortex of 7 calves and consisted of segmental degeneration and loss of Purkinje cells, and axonal swellings. The clinical signs and pathological findings were consistent with bovine familial convulsions and ataxia, which has not been described previously in Australia. The clinical signs were not attributable to the lesions observed in the cerebellum and an underlying electrophysiological abnormality is proposed. The aetiology of the condition is probably genetic and appears to have a multifactorial basis.     

Degenerative myelopathy associated with cobalamin deficiency in a cat

A severe myelopathy was observed in a 9-year-old neutered male cat with a clinical history of chronic pancreatitis associated with deficiency of serum cobalamin and folates concentrations, and progressive spinal ataxia. The spinal cord lesions mainly involved the dorsal columns of the caudal cervical and cervico-thoracic segments, and were characterized by diffuse vacuolated myelin sheaths and axonal degeneration, marked gliosis, fibrosis and presence of gitter cells. The pancreas showed severe atrophy of the exocrine tissue, periductular fibrosis and infiltration of inflammatory cells, consistent with chronic interstitial pancreatitis. This condition can be accountable for cobalamin deficiency, as the pancreas is the only source of intrinsic factor in cats. The spinal cord lesions in the cat of this report resembled the subacute combined degeneration of the spinal cord described in human beings with cobalamin deficiency and hence a similar pathogenetic mechanism is hypothesized.     

Equine laryngeal hemiplegia. Part V. Central nervous system pathology

Evidence of long central nerve fibre degeneration (axonal spheroids) in the lateral cuneate nuclei was found in all eight Thoroughbreds affected clinically and subclinically with equine laryngeal hemiplegia, but in only one of six control animals. It was considered that these spheroids may signify a central nervous component of the disease process of laryngeal hemiplegia although until further investigations are performed no firm conclusions regarding the relationship of these findings with laryngeal hemiplegia could be made. Examination of the left and right nucleus ambiguus of clinical and subclinical laryngeal hemiplegic horses revealed no pathological alterations.     

Sensory and motor neuropathy in a Border Collie

A 5-month-old female Border Collie was evaluated because of progressive hind limb ataxia. The predominant clinical findings suggested a sensory neuropathy. Sensory nerve conduction velocity was absent in the tibial, common peroneal, and radial nerves and was decreased in the ulnar nerve; motor nerve conduction velocity was decreased in the tibial, common peroneal, and ulnar nerves. Histologic examination of nerve biopsy specimens revealed considerable nerve fiber depletion; some tissue sections had myelin ovoids, foamy macrophages, and axonal degeneration in remaining fibers. Marked depletion of most myelinated fibers within the peroneal nerve (a mixed sensory and motor nerve) supported the electrodiagnostic findings indicative of sensorimotor neuropathy. Progressive deterioration in motor function occurred over the following 19 months until the dog was euthanatized. A hereditary link was not established, but a littermate was similarly affected. The hereditary characteristic of this disease requires further investigation.     

Equine degenerative myeloencephalopathy in Lusitano horses

Background

Equine degenerative myeloencephalopathy (EDM) is a neurodegenerative disorder that has been previously associated with low vitamin E concentrations.

Objective

To describe the clinical, electrophysiologic, and pathologic features of EDM in a group of related Lusitano horses.

Animals

Fifteen Lusitano horses.

Procedures

Neurologic examinations were conducted, and serum vitamin E concentrations were measured. Three neurologically abnormal horses were further evaluated by ophthalmologic examination, electroretinography, electroencephalography, muscle and nerve biopsies, and post‐mortem examination.

Results

Six horses appeared neurologically normal, 6 were neurologically abnormal, and 3 had equivocal gait abnormalities. Abnormal horses demonstrated ataxia and paresis. An inconsistent menace response was noted in 4 neurologically abnormal horses and in 1 horse with equivocal findings. All horses had low serum vitamin E concentrations (<1.5 ppm). Ophthalmologic examinations, electroretinograms, electroencephalograms, and muscle and peripheral nerve biopsies were unremarkable in 3 neurologically abnormal horses. At necropsy, major neuropathological findings in these horses were bilaterally symmetric, severe, neuro axonal degeneration in the gracilis, cuneatus medialis, cuneatus lateralis, and thoracicus nuclei and bilaterally symmetric axonal loss and demyelination mainly in the dorsolateral and ventromedial tracts of the spinal cord. A diagnosis of EDM was made based on these findings. Pedigree analysis identified 2 sires among the affected horses.

Conclusions and Clinical Relevance

Equine degenerative myeloencephalopathy is a neurodegenerative disorder that causes ataxia and, in severe cases, paresis, in young Lusitano horses. The disease appears to have a genetic basis, and although vitamin E deficiency is a common finding, low serum vitamin E concentrations also may occur in apparently unaffected related individuals.     

Subacute necrotising encephalopathy in an Alaskan husky

A 29-month-old female Alaskan husky was presented recumbent, tetraparetic and in a state of dementia, with blindness and cranial nerve deficits. The dog's progress was followed for over two months, as the signs resolved to an non-progressive mild hypermetria with slight proprioceptive ataxia, a diminished menace response and inability to prehend food. Magnetic resonance imaging (MRI) revealed bilateral cavitation extending from the thalamus to the medulla, with less pronounced degenerative lesions in the caudate nucleus, putamen and claustrum. Cerebrospinal fluid lactate and pyruvate concentrations were in their normal ranges. Necropsy and histological examination confirmed the MRI findings as well as neuronal degeneration of the cerebellar cortex in the vermis and degenerative changes in the neocortex at the depths of the cerebral sulci. In view of the similarity of lesions to subacute necrotising encephalomyelopathy, known as Leigh's disease in humans, a tentative diagnosis of a mitochondrial encephalopathy was made.     

Clinicopathological features of canine neuroaxonal dystrophy and cerebellar cortical abiotrophy in Papillon and Papillon-related dogs

Neuroaxonal dystrophy (NAD) was examined in two Papillon dogs and a mix breed dog between Papillon and Chihuahua. In addition, cerebellar cortical abiotrophy (CCA) in a Papillon dog, which had similar clinical and magnetic resonance imaging (MRI) features to those of NAD, was also investigated. The common clinical symptoms of all dogs affected with NAD and CCA, were pelvic limb ataxia and cerebellar ataxia including intention tremor, head tremor, and hypermetria in the early onset. These clinical signs were progressed rapidly, and two dogs with NAD were euthanized by owner's request and the other two died by aspiration pneumonia. MRI examinations and gross observations at necropsy revealed moderate to severe cerebellar atrophy in all cases of NAD and CCA. The most typical histological change of NAD was severe axonal degeneration with marked spheroid-formation in the dorsal horn of the spinal cords, the nuclei gracilis, cuneatus, olivalis and its circumference in the medulla oblongata. The spheroids were characterized as large eosinophilic or granular globes within the enlarged myelin sheaths, sometimes accompanied by moderate accumulation of microglias and/or macrophages. In contrast, such spheroid formation was minimal in the brain of CCA. In the cerebellum, mild to moderate loss of the Purkinje and granular cells were recognized in three dogs with NAD, whereas these changes were more prominent in a dog with CCA. Although the clinical signs and MRI findings relatively resembled between NAD and CCA, the histopathological features considered to be quite differ, suggesting distinct pathogenesis and etiology. Since both NAD and CCA are proposed as the autosomal recessive hereditary disorders, careful considerations might be needed for the breeding of Papillon and Chihuahua dogs.     

Peripheral nerve lesions in a case of equine motor neuron disease.

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.     

Neuronal vacuolation, myelopathy and laryngeal neuropathy in a mixed-breed dog

A bilateral and symmetrical neuronal vacuolation associated with spinal cord white matter degeneration and laryngeal neuropathy was observed in a 12-week-old male mixed-breed dog with a history of progressive pelvic limbs ataxia. On clinical examination, signs included inspiratory stridor, spinal ataxia, tetraparesis, and proprioceptive deficits more severe in the pelvic limbs. Examination of the larynx showed bilateral laryngeal paralysis and electromyography revealed fibrillation potentials restricted to the intrinsic laryngeal muscles. Clinical and pathological findings resembled the syndrome of neuronal vacuolation and spinocerebellar degeneration described in Rottweiler dogs. This is the first report of a similar disorder in a dog different from Rottweiler.     

Progressive tetraparesis and laryngeal paralysis in a young Rottweiler with neuronal vacuolation and axonal degeneration: an Australian case

A 5-month-old female Rottweiler dog was diagnosed to have a neurodegenerative disease that has been recently report ed in Rottweilers from North America and Europe. The dog was presented with progressive signs of ataxia, tetraparesis and inspiratory stridor. The clinical investigation included analysis of CSF, radiography, myelography and electrophysiolog-ical testing. No evidence of vertebral malformation or inflammatory CNS disease was identified. Bilateral laryngeal paraly sis was identified in the lightly anaesthetised dog. Electromyography showed abnormal spontaneous activity from the intrin sic musculature of the larynx. At necropsy there were no gross abnormalities of the nervous system but there was atrophy of the dorsal cricoarytenoid muscles of the larynx. There were widespread histological abnormalities throughout the ner vous system including neuronal vacuolation, spongiform changes in the neuropil and axonal degeneration which was most prominent in the spinal cord. These clinical and pathological findings are consistent with the diagnosis of a new neurode-generative disease reported from North America and Europe. This diagnosis is of particular significance in Australia where transmissible spongiform encephalopathies have not been identified.     

Leukoencephalomyelopathy in specific pathogen-free cats

Investigations were carried out on 8 specific pathogen-free cats (5 male and 3 female) from a colony experiencing "outbreaks" of progressive hind limb ataxia in 190 of 540 at-risk animals ranging from 3 months to 3 years old. These studies identified moderate to severe bilateral axonal degeneration within white matter regions of the cervical, thoracic, and lumbar spinal cord and in the white matter of the cerebral internal capsule and peduncle, in the roof of the fourth ventricle and inferior cerebellar peduncle, and in the external arcuate and pyramidal fibres of the medulla. There were varying degrees of accompanying microgliosis, astrocytosis, and capillary hyperplasia. Such a clinicopathologic syndrome, termed feline leukoencephalomyelopathy, has previously been described in cat colonies in Britain and New Zealand, although its etiology has not been determined. The degenerative nature of the lesions and their bilateral distribution suggest possible nutritional, metabolic, or toxic causes. Although these findings provide circumstantial evidence that the exclusive feeding of a gamma-irradiated diet of reduced vitamin A content is associated with the development of the neuronal lesions, further tissue micronutrient and antioxidant analysis will be required to support this hypothesis.     

Clinical characterization of a familial degenerative myelopathy in Pembroke Welsh Corgi dogs

BACKGROUND: Adult dogs with degenerative myelopathy (DM) have progressive ataxia and paresis of the pelvic limbs, leading to paraplegia and euthanasia. Although most commonly reported in German Shepherd dogs, high disease prevalence exists in other breeds. OBJECTIVE: Our aim was the clinical and histopathologic characterization of familial degenerative myelopathy (FDM) in Pembroke Welsh Corgi (PWC) dogs. ANIMALS: Twenty-one PWCs were prospectively studied from initial diagnosis until euthanasia. METHODS: Neurologic examination, blood tests, cerebrospinal fluid (CSF) analysis, electrodiagnostic testing, and spinal imaging were performed. Concentrations of 8-iso-prostaglandin F2alpha (8-isoprostane) were measured in CSF. Routine histochemistry was used for neuropathology. Deoxyribonucleic acid and pedigrees were collected from 110 dogs. RESULTS: Median duration of clinical signs before euthanasia was 19 months. Median age at euthanasia was 13 years. All dogs were nonambulatory paraparetic or paraplegic, and 15 dogs had thoracic limb weakness at euthanasia. Electrodiagnostic testing and spinal imaging were consistent with noncompressive myelopathy. No significant difference was detected in 8-isoprostane concentrations between normal and FDM-affected dogs. Axonal and myelin degeneration of the spinal cord was most severe in the dorsal portion of the lateral funiculus. Pedigree analysis suggested a familial disease. CONCLUSIONS AND CLINICAL IMPORTANCE: Clinical progression of FDM in PWC dogs was similar to that observed in other breeds but characterized by a longer duration. Spinal cord pathology predominates as noninflammatory axonal degeneration. Oxidative stress injury associated with 8-isoprostane production is not involved in the pathogenesis of FDM-affected PWC dogs. A familial disease is suspected.