A progressive axonopathy of Boxer dogs affecting the central and peripheral nervous systems

Five Boxer dogs with a new neurological disease are described. There is a progressive ataxia and weakness, initially in the hind-legs but later involving forelegs. The onset of signs is usually around 6 months of age although an older dog was affected. Proprioceptive function, muscle tone and tendon reflexes are diminished or absent while pedal reflexes and pain sensation are preserved. Muscle atrophy is minimal. The peripheral nerves are depleted in myelinated fibres. Nerve roots and, to a lesser extent, peripheral nerves show demyelination/remyelination changes and in the cervical ventral roots in particular, regenerative clusters are present. Forelimb muscles show evidence of re-innervation. In the CNS numerous swollen axons are present. The dorsolateral and ventral columns of the spinal cord are affected throughout their length. In the brain a number of nuclei and tracts, particularly in the lower brain stem, are affected and the superior olives are severely involved. The cerebral cortex and subcortical white matter appear normal. Various portions of the auditory and optic pathways are affected pathologically as are a number of cranial nerves. The axonal swellings contain a number of organelles including smooth endoplasmic reticulum, disordered neurofilaments, vesicles and mitochondria. The disease may be specific to Boxer dogs and may be inherited.     

Peripheral neuropathy in cats with inherited primary hyperchylomicronaemia

Primary hyperlipoproteinaemia (hyperchylomicronaemia) with a slight increase in very low density lipoprotein) is described in 20 cats. Fasting hyperlipaemia, lipaemia retinalis and peripheral neuropathies were the most frequently detected clinical signs. The disease is thought to be inherited as an autosomal recessive trait but the exact mode of inheritance has not been determined. Affected cats showed reduced lipoprotein lipase activity measured after heparin activation compared with the response in normal cats. Plasma triglyceride and cholesterol were increased in all the cats with the major proportion of triglyceride and cholesterol being present in chylomicrons. The peripheral nerve lesions were caused by compression of nerves by lipid granulomata. It is probable that the lipid granulomata result from trauma because the nerves most often affected were at sites like the spinal foraminae where they were susceptible to trauma.     

Pathological aspects of Australian Stringhalt.

Nine horses with clinical signs of Australian Stringhalt were killed and tissues collected for a detailed pathological study. Lesions were limited to peripheral nerves and muscles. The most severely affected nerves were the superficial and deep peroneal, distal tibial, plantar digital, volar and recurrent laryngeal nerve with changes characterised by a selective loss of large diameter myelinated fibres with various degrees of demyelination, fibrosis, Schwann cell proliferation and onion-bulb formation. A routine evaluation of the brain and spinal cord by light microscopy failed to reveal any consistent abnormalities. Morphometric analysis of deep peroneal and recurrent laryngeal nerves confirmed the reduced number of large diameter myelinated axons. Teased fibre preparations of these nerves did not show any abnormalities in internodal distance. The most severe muscle lesions were in the long and lateral digital extensors, cranial tibial, dorsal cricoarytenoid, gracilis and lateral deep digital flexor with extensive atrophy of fibres and diffuse fibrosis. Histochemical evaluation of the long digital extensor from 3 affected horses showed an abnormally wide distribution in fibre size and a reduction in type II fibres compared with controls. These lesions are consistent with a distal axonopathy leading to neurogenic muscle atrophy. The distribution of neuromuscular lesions in Australian Stringhalt may be explained by the susceptibility of longer, larger myelinated nerve fibres to injury, but the cause for this distal axonopathy remains unknown.     

Polyneuropathy associated with forage sources in Norwegian horses

BACKGROUND: Cases of hindlimb digital extensor weakness of unknown etiology have been observed in Norway since 1995. HYPOTHESIS: We hypothesized that the observed bilateral extensor weakness was attributable to neuropathy of the distal nerves and that this was related to environmental factors, possibly dietary. ANIMALS: Seventy-five horses with digital extensor weakness occurring from 1995 to 2004 are described. METHODS: Eleven horses were examined at The Norwegian School of Veterinary Science, and the medical records of 64 horses seen in ambulatory practice were reviewed. RESULTS: There was no apparent sex, age, or breed predilection, but the majority were horses kept for pleasure or breeding purposes. Clinical signs varied from intermittent knuckling of the hindlimbs to paraplegia. Some horses showed no or only slow progression of signs, whereas others developed severe signs within hours. No other neurologic deficits were detected in any of the horses. Epidemiologic data and laboratory results were not supportive of an infectious etiology. The only common factor for all affected horses seemed to be feeding big bale silage or, occasionally, hay of poor microbiologic quality. Forty of the 75 horses were euthanized. Histopathologic examination of peripheral nervous tissue was performed in 22 horses, all of which had neuronal fiber degeneration. The majority of horses with mild signs recovered after 5-6 months of rest. CONCLUSIONS AND CLINICAL IMPORTANCE: Clinical signs correlated with polyneuropathy involving sciatic nerves.     

Peripheral neuropathy associated with dietary riboflavin deficiency in the chicken. I. Light microscopic study

Chickens fed a riboflavin-deficient diet from hatching had leg weakness and paralysis as early as 12 days of age. Signs worsened through day 16; after 35 days, recovery was evident. Sciatic nerves from affected chickens were enlarged. Significant microscopic lesions were confined to peripheral nerves and included tissue separation (suggesting interstitial edema), Schwann cell swelling, perivascular leukocytic infiltration, and segmental demyelination accompanied by accumulation of osmiophilic debris in Schwann cell cytoplasm. Axon degeneration was present, but was not a primary lesion. Acid phosphatase enzyme activity of Schwann cells was increased in affected nerves. These results demonstrate that dietary riboflavin deficiency causes a demyelinating peripheral neuropathy in young, rapidly growing chickens.     

Canine fucosidosis: clinical findings

The clinical course of canine fucosidosis, a neurovisceral lysosomal storage disease, is described from observations of 31 affected English Springer Spaniels. The diagnosis of fucosidosis was suggested by the development of multifocal neurological signs in the second year of life and confirmed by a deficiency of alpha-L-fucosidase activity in plasma and leucocytes. The progressive motor and mental deterioration was similar in all dogs and no affected animal survived to four years of age. Alpha-L-fucosidase activity in plasma was <0·05 μ/1 in all cases. The activity in leucocytes and other tissues was < 5 per cent of that of normal dogs. Vacuolated leucocytes occurred in cerebrospinal fluid, blood and bone marrow. The enlargement of peripheral nerves which is observed at autopsy could be detected by palpation of the ulnar nerve in advanced disease, however the results of electrodiagnostic studies were within normal limits. The clinical signs and pathological changes were found to be remarkably consistent from case to case making it an excellent model for investigating therapeutic strategies in human lysosomal storage disorders.     

Nerve sheath tumours in the dog and cat

Schwannomas were diagnosed in twelve dogs and five cats at Massey University Small Animal Clinic and Hospital over a 15-year period (1977-92). A further two feline cases were reported at the Batchelar Animal Health Laboratory. In six dogs, the tumour involved nerves of the brachial plexus. Clinical signs observed in these dogs were forelimb lameness, muscle wasting and pain on movement of the affected limb or neck. Hindlimb paresis was observed in two dogs. Surgical excision of the brachial plexus tumour was attempted in one dog, leading to an 8-month remission of signs. In one dog, the tumour involved the sacral nerves, and in two dogs the cranial nerves were affected. Three dogs had skin nodules. Seven of the twelve affected dogs were destroyed. In five cats, the tumours developed on the carpus, tarsus or interdigital area of a forelimb or hindlimb as a slowly developing nodular lesion. In the other two cats, the site of the tumour was the flank and the lateral thigh respectively. Surgical excision of the tumour was successful in three cats.     

A progressive neuronopathy in the young cairn terrier

The clinical signs and neuropathological changes of a nervous disease of pedigree cairn terriers are described. Three animals, of both sexes, between five and seven months of age showed hind leg weakness, quadriparesis, ataxia, loss of superficial and deep reflexes and tremor of the head. Pathologically there was chromatolysis of neurons in the spinal cord and brain stem. Although Wallerian-type degeneration was present in the spinal cord and peripheral nerves, its severity did not correlate with the intensity of the neuronal changes. This suggests that the chromatolysis observed may reflect a primary neuronal abnormality rather than represent a secondary change resulting from a primary degeneration of peripheral axons. Although the age of onset and some of the clinical signs are similar to those seen with globoid cell leucodystrophy (an inherited disease which also affects cairn terriers), the presence of lower motor neuron paralysis and the absence of signs of severe brain involvement in progressive neuronopathy should enable the conditions to be distinguished clinically.     

Histological and ultrastructural evidence that recurrent laryngeal neuropathy is a bilateral mononeuropathy limited to recurrent laryngeal nerves

Reasons for performing study: Recurrent laryngeal neuropathy (RLN) is a common and debilitating peripheral nerve disease of horses, but it remains unclear if this disease is a mono‐ or polyneuropathy. An understanding of the distribution of the neuropathological lesions in RLN affected horses is fundamental to studying the aetiology of this very significant disease of tall horses. Objective: To determine whether RLN should be classified as a mono‐ or polyneuropathy. Methods: Multiple long peripheral nerves and their innervated muscles were examined systematically in 3 clinically affected RLN horses Results: Severe lesions were evident in the left as well as right recurrent laryngeal nerves in all horses, both distally and, in one case, also proximally. No primary axonal lesions were evident in other nerves nor were changes found in their innervated muscles. Conclusions: RLN is not a polyneuropathy but should be classified as a bilateral mononeuropathy. Potential relevance: Genetic and local factors specifically affecting the recurrent laryngeal nerves in RLN‐affected horses should now be investigated further.     

Hereditary myopathy in Labrador retrievers: a morphologic study

Skeletal muscle and peripheral nerve were obtained over several years from 12 Labrador retrievers with signs of hereditary myopathy. Biopsy and necropsy samples were examined by histology and histochemistry. Despite normal findings in peripheral nerves, a wide range of morphologic changes were observed in muscle including features generally considered characteristic of neurogenic disease. These included small and large muscle fiber group atrophy, presence of small angular fibers, and occasional fiber type grouping. Other prominent changes in muscle were increased numbers of internal nuclei, architectural disturbances, type II fiber deficiency, necrosis, regeneration, and fibrosis--all of which are more usually associated with destructive myopathies or muscular dystrophies. The pathology of this condition, therefore, includes features of both neurogenic and myopathic disease, while the underlying pathophysiology remains unclear.     

Diagnostic exercise: astrocytoma with involvement of medulla oblongata, spinal cord, and spinal nerves in a raccoon (Procyon lotor)

Neoplasms affecting the central and peripheral nervous systems of wild animals are extremely rare. Described are clinical signs and pathologic and immunohistochemical findings in an adult female raccoon (Procyon lotor) with an astrocytoma that involved medulla, cervical spinal cord, and roots of the cervical spinal nerves. Microscopically, the neoplastic cells revealed some pleomorphism but generally had fusiform morphology and showed moderate numbers of mitotic figures. Glial fibrillary acidic protein was demonstrated within the neoplastic cells by immunohistochemistry. This appears to be the only reported case of astrocytoma that involved multiple anatomic sites in the central nervous system of this raccoon.     

Bilateral laryngeal paralysis in the horse

Four two-year-old Thoroughbreds suffered an acute gastrointestinal illness shortly after dosing with mineral oil which was thought to have been contaminated with an organophosphate compound. Three weeks later all four were noted to be dyspnoeic and endoscopic examination showed that they had developed bilateral laryngeal paralysis. Two of the horses died during severe bouts of dyspnoea six and eight months later and the third was killed shortly thereafter. Examination of the left and right recurrent laryngeal nerves from these horses showed a severe loss of myelinated fibres distally, especially in the left nerve. A similar but less severe lesion was seen in other long peripheral nerves, including the phrenic and digital nerves of the third horse. The spinal cord in two horses showed evidence of mild axonal degeneration which was not related to a particular tract or location. The fourth horse had bilateral laryngeal paralysis two years later. The acute clinical signs and delayed neurological sequelae seen in these horses were strongly suggestive of accidental organophosphate toxicity.     

Clinical, diagnostic and biochemical features of generalised glycogenosis type II in Brahman cattle

SUMMARY Clinical, diagnostic and biochemical features of generalised glycogenosis are described In 96 Brahman-type calves. Typically the calves were presented when about 6 months of age, with III-thrift and muscular weakness as the most common signs. Acidic α-glucosidase activity was reduced in peripheral blood lymphocytes and skeletal muscle. Muscle glycogen concentration was consistently higher in affected animals than In clinically normal cattle. Other observations in affected calves Included elevation of serum aspartate amlnotransferase and creatine kinase activities and excessive amounts of high molecular weight oligosaccharides in urine. Fine cytoplasmic vacuolation of neurones In the brain and spinal cord, skeletal muscle, myocardlum and of Purkinje fibres were consistent histological observations. Periodic acid-Schlff staining revealed the presence of glycogen-like material In peripheral blood lymphocytes of all affected calves, Indicating that this is a useful aid for the diagnosis of glycogenosis. While 3 of the 96 calves showed somewhat different clinical signs, the similarity of pathology and the biochemical and clinical evidence in the remainder suggested that, In these animals, the disease was expressed as a single syndrome.     

Acute bilateral trigeminal neuropathy associated with nervous system lymphosarcoma in a dog

A nine-year-old dog presented with clinical signs consistent with bilateral trigeminal neuropathy. Multicentric lymphoma was diagnosed, and neoplastic lymphocytes were identified in the cerebrospinal fluid. Electromyography revealed spontaneous activity in temporal and masseter muscles. Histopathological examination demonstrated neoplastic cell invasion of temporal and masseter myofibers and of multiple peripheral nerves, including the trigeminal nerve. Central nervous system pathology consisted primarily of spinal root and leptomeningeal lymphoid cell infiltration with relative sparing of spinal cord and brain parenchyma.     

Acquired spinal cord and peripheral nerve disease.

Acquired spinal cord diseases in ruminants result most commonly from infectious, traumatic, metabolic/nutritional, or toxic causes and rarely from neoplasia. Clinical signs of spinal cord disease depend on the neuroanatomic location of the lesion. Acquired spinal cord diseases including vertebral osteomyelitis/spinal abscess, cauda-equina disease, enzootic ataxia, lymphosarcoma,polyradiculoneuritis, and degenerative myeloencephalopathy are discussed. Acquired peripheral nerve disease in cattle most often is a result of injury, and most commonly only one limb is involved.Peripheral nerve injuries frequently occur secondary to myopathy in recumbent adult cattle. In small ruminants, peripheral nerve injury seems less common, most likely due to their smaller size,but may occur from predator wounds or iatrogenically following intramuscular drug administration. Injury to the brachial plexus and radial, suprascapular, sciatic, femoral, and obturator nerves is discussed.     

A familial peripheral neuropathy and glomerulopathy in Gelbvieh calves

Nine Gelbvieh calves originating in four herds and clinically presenting with rear limb ataxia/paresis had histopathologically confirmed peripheral neuropathy and a proliferative glomerulopathy. Degenerative lesions were severe in peripheral nerves, dorsal and ventral spinal nerve roots, and less marked in dorsal fasciculi of the spinal cord. Cell bodies of spinal ganglia were minimally diseased; ventral horn neurons occasionally had central chromatolysis and nuclear displacement. Glomerular lesions ranged from mild mesangial hypercellularity to glomerulosclerosis. Pedigree analysis of affected animals from one herd indicated a strong familial relationship and probable hereditary basis for the syndrome.     

Are ovine fenugreek (Trigonella foenum‐graecum) staggers and kangaroo gait of lactating ewes two clinically and pathologically similar nervous disorders?

Fenugreek staggers has occurred in sheep in Victoria, as both an acute and a chronic syndrome. Signs included quadraparesis, a high stepping fore limb gait and a 'bunny-hopping' hind limb gait. Changes consistent with acute oedema were found in the brain and spinal cord of acute cases, and Wallerian degeneration in the peripheral nerves of chronic cases. Kangaroo gait occurred in ewes in New South Wales, and the clinical signs and microscopic changes were remarkably similar to those of fenugreek staggers. Although the diet associated with each is different the causal agent may be the same.     

Canine neural angiostrongylosis: the clinical and therapeutic features of 55 natural cases

The clinical features of 55 naturally occurring cases of neural angiostrongylosis caused by the parasite Angiostrongylus cantonensis are described. The principal clinical feature is an ascending paresis of varying severity, mainly effecting the limbs and bladder. In severely affected animals the cranial nerves and central nervous system are affected. A distinguishing clinical sign is a variable severe lumbar hyperalgesia. For prognostic purposes the severity of the disease is divided into 3 grades. Recovery occurs in the first 2, however in the third, the most severe grade, animals do not recover. Corticosteroids and supportive nursing facilitate recovery and lessen the residual neurological dysfunction. Anthelmintics were included in the therapeutic regimen but their use worsened the signs. Death was recorded in association with the use of anthelmintics in cases that should have otherwise recovered.     

A familial degenerative neuromuscular disease of Gelbvieh cattle.

A degenerative skeletal muscle disease with vascular, neurologic, and renal lesions and a probable familial distribution was identified in 4-20-month-old purebred Gelbvieh cattle. Thirteen affected animals were confirmed from 6 separate beef herds, with a mortality rate of 100%. Clinical signs in affected animals consisted of ataxia, weakness, and terminal recumbency. Gross and histologic muscle lesions were indicative of nutritional myopathy of ruminants, with a lack of myocardial lesions in most cases and only rare myocardial changes in a few animals. Acute to chronic lesions in most large skeletal muscle groups consisted of degeneration, necrosis, regeneration, fibrosis, and atrophy. Fibrinoid necrosis of arterioles was a common feature in multiple tissues. Lesions in the spinal cord white matter and peripheral nerves consisted of degeneration of the dorsal columns and axons, respectively. Changes in the kidneys consisted of chronic interstitial nephritis with fibrosis, hyaline droplet change and tubular epithelial vacuolar change and were most severe in the older calves. Intracytoplasmic myoglobin and iron were demonstrated within the hyaline droplets in degenerate renal cortical tubular epithelial cells. Vitamin E levels were deficient in most (6/7) of the animals tested. Investigation of the pedigree of affected animals revealed a common ancestry for all but 1 of the animals whose parentage could be traced. This investigation suggests that a hereditary metabolic defect, possibly involving antioxidant metabolism, could be responsible for this condition. Renal disease, possibly secondary to myoglobinuria, may be unique to this bovine condition.