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.     

ATAXIA AND URINARY INCONTINENCE IN CATTLE GRAZING SORGHUM

After grazing forage sorghum and grain sorghum regrowth, 54 of 330 breeding cows became ataxic and developed urinary incontinence. Three cows became recumbent, 2 of which died and the third was killed and autopsied. Wallerian degeneration of the white matter of the spinal cord, cerebellar peduncles and cerebellum was seen histologically. Other affected animals began to recover on removal from the crop, complete clinical recovery taking from a few days to over a month. About 5% of affected cows develped purulent cystitis.     

Leucoencephalomalacia and Cerebral White Matter Vacuolar Degeneration in Two Related Labrador Retriever Puppies

Two Labrador Retriever dogs from a common dam had similar neurological deficits consisting of cortical blindness, dullness, and loss of previously learned habits. Both were examined at 5 months of age, and histopathological examination revealed leucoencephalomalacia and vacuolar degeneration of the cerebral white matter. Histopathologic findings in these 2 dogs differed from those reported previously in Labrador Retrievers with spongy degeneration of central nervous system white matter. A nonlittermate full sibling to 1 of these dogs was examined at 1.5 years of age for similar clinical signs that did not progress for the next 25 months.     

Retinal and optic nerve degeneration in cattle after accidental acrylamide intoxication

A herd of cattle was accidentally exposed to monomeric acrylamide and N-methylolacrylamide. Seven cattle underwent repeated examinations during 6–8 months after exposure. Abnormal pupillary light reflexes (PLR) were observed in one cow. Ophthalmoscopic examination showed progressive retinal degeneration and degenerative changes in the optic nerve heads in this cow. Light and electron microscopic examination revealed pathological changes in the retinae and optic nerves consistent with chronic stages of acrylamide toxicity. Ophthalmic examination and light microscopy did not reveal abnormalities in the retinae or optic nerves in either the rest of the cattle from the herd or in offspring of exposed cattle.     

Ossifying fibroma as a cause of blindness in a 5-year-old Quarter Horse gelding

A 5-year-old Quarter Horse gelding presented to Texas A&M University Veterinary Medical Teaching Hospital with a several week history of bilateral blindness. Neurological deficits included an absent menace response and severe atrophy of the optic nerve head in the left eye (OS) as well as decreased vision in the right eye (OD). Advanced imaging consisting of computed tomography (CT) and magnetic resonance imaging (MRI) confirmed a large mass in the base of the skull invading the sinuses and asymmetrically compressing the optic nerves rostral to the optic chiasm. Due to the size and location of the mass as well as severity of associated neurological signs, humane euthanasia was elected. Necropsy examination identified a large mass effacing the sphenopalatine sinuses and compressing the optic nerves. Histologically, the mass was identified as an ossifying fibroma (OF) and degeneration of the optic nerves was confirmed. As an OF in this location has never been described in a horse, this case demonstrates a new differential for blindness in horses.     

Gross and histopathological findings in unusual lesions caused by Streptococcus suis in pigs. II. Central nervous system lesions.

Subacute meningoencephalitis or meningoencephalomyelitis caused by Streptococcus suis was diagnosed in 53 pigs over a four-year period. Affected pigs averaging 11 weeks of age with a range from five days to 26 weeks, had been treated with antibiotics and had partially recovered. Hyperemia of meningeal vessels and modest increase in cerebrospinal fluid were the most common gross central nervous system lesions. Histologically, fibrin, edema and a mixture of inflammatory cells were present in meninges and choroid plexus. Linear and perivascular infiltrates of neutrophils and mononuclear inflammatory cells invaded the brain and spinal cord and similar infiltrates were in lumina of ventricles and the spinal canal. Inflammatory cells also invaded the superficial layers of the brain directly from the overlying meninges. Bilateral subacute optic perineuritis and Gasserian ganglioneuritis also occurred. Segmental cortical necrosis of cerebellar folia characterized by degeneration, necrosis, neuronophagia and drop out of groups of Purkinje cells was a distinct lesion seen in 27 of the 53 pigs. Mild spongiosis of white matter in the cerebellum and brain stem accompanied these changes.     

Lesions in bovine progressive degenerative myeloencephalopathy ("Weaver") of Brown Swiss cattle

Gross changes and other necropsy findings in 36 purebred Brown Swiss cattle affected with bovine progressive degenerative myeloencephalopathy were nonspecific. Primary microscopic lesions were confined to the central nervous system, specifically the white matter of the spinal cord, axons in some brainstem nuclei, and Purkinje cells of the cerebellar cortex. Spinal cord lesions involved only the white matter and consisted of axonal degeneration, loss of axons and myelin, and status spongiosus. Axonal degeneration was characterized by swelling and fragmentation of the axoplasm or formation of large, discontinuous swellings referred to as spheroids. Lesions were qualitatively similar at all levels, but quantitatively dissimilar in the same funiculi at different levels. Both ascending and descending fibers were involved but correlation to specific fasciculi was not evident. Lesions always were most severe in thoracic spinal cord segments. Little or no astroglial response, no inflammatory response, and no involvement of gray matter were observed in the spinal cord. Cerebellar lesions were limited to selective degeneration and loss of Purkinje cells and occasional swelling of Purkinje cell axons (torpedos) in the granular layer of the cerebellar cortex. Brainstem lesions were inconsistent and limited to occasional axonal swelling in brainstem nuclei. The pathogenesis of bovine progressive degenerative myeloencephalopathy is unknown and possible mechanisms were discussed. The disease exhibits a familial pattern in Brown Swiss cattle and may be hereditary. Extraneural lesions were considered secondary to central nervous system lesions.     

Spongy degeneration of the central nervous system in two canine littermates

Progressive dysmetria was observed at four months and six months of age in two female Labrador retriever littermates. Neurological examinations indicated a cerebellar disorder. Laboratory analyses were normal. The dogs were studied clinically until they were killed for necropsy at nine months and eleven months of age. Both dogs had normal brain size, shape, and calvarial symmetry; the older dog had body weight loss, reduced brain weight, and muscle atrophy. Microscopically, there were vacuoles, hypertrophied fibrous astrocytes, myelin loss, and prominent blood vessels, distributed symmetrically in the subcortical and deep white matter of all lobes of the cerebrum; in the folial and deep white matter of the cerebellum; in the tracts of some cranial nerves; in the thalamic area, midbrain and brainstem; and in the white matter of the spinal cord. There was no significant myelinolysis, inflammation, or axonal degeneration. Ultrastructurally, there were intramyelinic vacuoles with separation of lamellae at intraperiod lines and larger spaces formed by coalescence of ruptured vacuoles. Hypertrophied fibrous astrocytes had abundant glial filaments, edematous cytosol, membrane-bound crystalline inclusions, dilated cytocavitary systems, and abnormal mitochondria. The clinical, histological, and ultrastructural findings resembled those reported for the juvenile form of Canavan's disease (van Bogaert and Bertrand type) in children.     

Spongy Degeneration with Cerebellar Ataxia in Malinois Puppies: A Hereditary Autosomal Recessive Disorder?

Background: There is a high incidence of hereditary degenerative diseases of the central nervous system in purebred dogs. Hypothesis: Cerebellar ataxia in Malinois puppies, caused by degenerative changes that predominate in cerebellar nuclei and the granular cell layer, is a hereditary disorder that is distinct from cerebellar cortical abiotrophies. Animals: Thirteen Malinois puppies with cerebellar ataxia. Methods: Retrospective study. Records of Malinois puppies with spongy degeneration of the cerebellar nuclei were analyzed including clinical signs, histopathological changes, and pedigree data. Results: Signs of cerebellar dysfunction were observed in puppies of both sexes from 5 different litters (1995–2009) of phenotypically normal parents. Clinical signs started before the age of 2 months and resulted in euthanasia of all puppies by the age of 13 weeks. Histopathology disclosed marked bilateral spongy degeneration of the cerebellar nuclei and vacuoles in the granular cell layer and foliate white matter of the cerebellum. In some puppies, discrete vacuoles in gray and white matter were present in other parts of the brain. Furthermore, spheroids and dilated myelin sheaths were observed. Pedigree data and segregation frequency support an autosomal recessive hereditary disorder. Conclusions and Clinical Importance: Malinois suffer from a hereditary spongiform degeneration that predominates in the cerebellum and causes an early onset of clinical signs with unfavorable prognosis. Future efforts should increase awareness among veterinarians and breeders and aim to identify underlying metabolic mechanisms and the affected genes.     

Anophthalmia and retinal degeneration associated with stenosis of the optic foramen in Fischer 344 rats

Bilateral anophthalmia was discovered in a male rat (No. 1) and unilateral anophthalmia was found in the left eye of two female rats (Nos. 2 and 3) derived from a Fischer 344 inbred colony. One male rat (No. 4), a littermate of No. 3, had externally normal eyes, but his left eye had severe retinal atrophy, which was detected by ophthalmoscopy. The eyelids in both eyes of No. 1 and in the left eyes of Nos. 2 and 3 were present. Radiography of the skull revealed small optic foramina on both sides of No. 1 and on the affected side of Nos. 2, 3, and 4. Histologically, both globes and optic nerves (ONs) of No. 1 and the left globe and ONs of Nos. 2 and 3 were completely missing. Diffuse retinal degeneration in the left globe and axonal degeneration in the left ON and the right optic tract were observed in No. 4. Dysplasia of the sphenoid bone associated with stenosis of the optic foramen was detected on the affected side of all rats. Thus, ON aplasia in anophthalmic rats and atrophic ON in a rat with retinal degeneration seem to be closely related to stenosis of the optic foramen.     

Blindness in goats following ingestion of Stypandra glauca

Twenty-seven of 427 Angora goats of mixed age became blind within a week of consuming large amounts of Stypandra glauca ("nodding blue lily"). A further 200 goats were depressed for several weeks, but most subsequently recovered. Blindness was associated with optic nerve neuropathy which is postulated to have followed compression of the optic nerves within the bony optic canals as a result of severe myelin oedema. Histologically, the intracanalicular portion of the optic nerve was sclerotic, while the intracranial portion of the optic nerve and the optic tracts were degenerating. The retrobulbar portion of the optic nerve was relatively unaffected. In addition, multifocal retinal photoreceptor degeneration was found ophthalmoscopically and histologically. The syndrome was not reproduced during a trial in which 2 goats were fed 4 and 20 kg of S. glauca harvested after it had finished flowering, more than 3 weeks after the first natural cases of blindness. Based on epidemiological and pathological data we propose that S. glauca is toxic to stock, but only for a short period while flowering in spring.     

Unilateral degeneration of retina and optic nerve in Fischer-344 rats

Unilateral degeneration of the retina and optic nerve was observed among Fischer-344 (F-344) rats fed a semi-purified synthetic feed. Further studies were conducted using standard cereal-based and synthetic diets. Beginning at 4 weeks of age, all experimental rats (169 F-344 rats) were fed various diets and were examined for morphologic and functional changes in the retina and optic nerve. No ocular lesions were observed in any F-344 rats prior to 21 weeks of age, whether fed a synthetic diet or a standard diet; however, approximately 16% (13/86) of the F-344 rats examined between 57 and 64 weeks of age developed unilateral degeneration of the retina and optic nerve. On the other hand, the F-344 rats fed the synthetic diet developed the degenerative lesions by 30 weeks of age, while the F-344 rats fed the standard diet did not develop lesions over this shorter time period. Degenerative changes of the affected retinas and optic nerves were closely related with functional abnormalities evaluated by electroretinogram and visual evoked potentials. In contrast with the F-344 rats, Long-Evans rats that were fed either the synthetic or standard diet up to the age of 68 weeks (77 rats) did not develop the ocular lesions. There was no apparent relationship of the development of the lesions with dietary modification, toxicity or trauma; thus, these observations appear to indicate that spontaneous unilateral degeneration of the retina and optic nerve occurs in F-344 rats and that these ocular lesions may be accelerated by the feeding of certain semi-purified synthetic diets.     

Suspected inherited cerebellar neuroaxonal dystrophy in collie sheep dogs

A cerebellar neuroaxonal dystrophy in working collie sheep dogs from two properties in New Zealand and one property in Australia is described. Clinical signs developed from 2-4 months of age and included hypermetria, wide-based stance, difficulty in maintaining balance, intention tremor and ataxia. Numerous spheroids, associated with mild Wallerian degeneration, were present in the central cerebellar, adjacent peduncular and folia white matter, and associated cerebellar roof and lateral vestibular nuclei. The history of several affected pups in litters from successive matings of the same sire and dam is suggestive of an autosomal recessive mode of inheritance.     

Suspected inherited cerebellar neuroaxonal dystrophy in collie sheep dogs

A cerebellar neuroaxonal dystrophy in working collie sheep dogs from two properties in New Zealand and one property in Australia is described. Clinical signs developed from 2–4 months of age and included hypermetria, wide-based stance, difficulty in maintaining balance, intention tremor and ataxia. Numerous spheroids, associated with mild Wallerian degeneration, were present in the central cerebellar, adjacent peduncular and folia white matter, and associated cerebellar roof and lateral vestibular nuclei. The history of several affected pups in litters from successive matings of the same sire and dam is suggestive of an autosomal recessive mode of inheritance.     

Hereditary encephalomyelopathy and polyneuropathy in an Alaskan husky

An Alaskan husky puppy was examined for a neurologic disease which began at six weeks of age with generalised paresis that progressed resulting in recumbency by 18 weeks. Thoracic limbs primarily exhibited lower motor neuron signs that included distal muscle atrophy and persistent elbow and carpal flexion that resisted manual extension. Pelvic limb signs primarily exhibited upper motor neuron and general proprioceptive deficits, but also included lower motor neuron signs. Abnormal vocalisation suggested a laryngeal paresis. Histopathologic lesions included a diffuse axonopathy and secondary demyelination in the nerves of the limbs and larynx and a similar bilaterally symmetrical degeneration in the spinal cord white matter suggestive of a dying back axonopathy. In addition, a degenerative process was present in nuclei in the brain stem and cerebellum. Recognition of this disease through clinical and pathologic examination in other related Alaskan Huskies suggested an autosomal recessive inherited disorder.     

Chronic cervical compressive myelopathy in horses: patterns of astrocytosis in the spinal cord

The distribution and morphology of fibrous astrocytes in the cervical spinal cord of normal horses and horses with chronic compressive myelopathy were demonstrated using immunohistochemical staining for glial fibrillary acidic protein. In the spinal cord from normal horses, astrocytes with stellate cell bodies and short processes were irregularly distributed in grey matter. In the white matter, their cell bodies were small and angular in areas adjacent to grey matter and larger and more stellate-shaped in the subpial area. Astrocyte processes were fine, and evenly distributed in a predominantly radial pattern in transverse sections of cord. Gliosis was marked in the spinal cords of horses with cervical compressive myelopathy. In the grey matter at the level of compression astrocytes were often enlarged and rounded, with short, blunt processes, but the gliosis was generally mild. In the white matter, gliosis was obvious in areas of nerve fibre swelling and degeneration at the level of compression and in areas of ascending and descending Wallerian degeneration. The fine radial pattern of astrocyte fibres was replaced by a dense, irregular arrangement. Gliosis persisted in the cords of chronically affected horses after active nerve fibre degeneration had subsided. The areas of gliosis coincided with the areas of Marchi staining for degenerating myelin and with areas of myelin loss in osmium tetroxide post-fixed tissue. Histological observations were consistent with astrocytes replacing areas of extracellular space that remained after nerve fibre degeneration. it is concluded that astrocytic gliosis is a prominent and persistent alteration of the spinal cord of horses with chronic cervical compressive myelopathy.     

HUMPY BACK OF SHEEP. CLINICAL AND PATHOLOGICAL OBSERVATIONS

Humpy back, a disease of Merino sheep in western Queesland, occurs during mustering for shearing. It is usually seen in summer 6-10 weeks after substantial rainfall and is thought to be caused by the ingestion of a toxic plant. The disease is characterised clinically by a short-stepping, stilted gait of the hind limbs, followed by lowering of the head, arching of the back and inability to continue walking. Histopathological examination of 8 cases from 5 properties revealed a Wallerian degeneration of the white matter throughout the length of the spinal cord with the ventral and lateral columns most severely affected. A similar degenerative change was seen in the posterior cerebellar peduncles of 3 of the sheep. A more severe hind limb incoordination with more extensive degeneration of the white matter of the spinal cord, medulla and cerebellum was seen in a case of humpy back of two years duration. Similar, but much milder, spinal cord lesions were found in apparently unaffected sheep from the same group as the sheep affected with humpy back on 2 properties. Severe myodegeneration of hind limb muscle groups was seen in 3 affected sheep. It was thought to be associated with the long rail journey (1500 km) to the laboratory after the sheep were affected in the field.     

Neuropathology of experimental 3-nitro-4-hydroxyphenylarsonic acid toxicosis in pigs

Twenty pigs were fed a diet containing 187.5 mg kg-1 of 3-nitro-4-hydroxyphenylarsonic acid (3-nitro). Ten pigs were euthanized at intervals up to 29 days, 3-nitro was withdrawn from the diet of the remaining pigs on day 30, and these animals were subsequently euthanized at intervals up to 49 days after commencement of the experiment. A nervous syndrome characterized by clonic convulsive episodes inducible by exercise, developed at day 11. Paraparesis was apparent at day 22 progressing to paraplegia by day 33 (3 days after cessation of 3-nitro feeding). Histopathologic examination revealed myelin and axonal degeneration in the white matter of the spinal cord coincident with the onset of nervous signs. Marchi-positive degeneration was present in the dorsal funiculus at cervical level at day 22. Lesions intensified with increasing duration of toxicosis and while degenerate fibers were seen in all funiculi, there was preferential involvement of the fasciculi gracilis and cuneatus, the peripheral regions of the ventral and lateral funiculi, and a discrete area of the dorsal region of the lateral funiculus. Peripheral and optic neuropathies were evident from day 32 but were always mild and focal. The experiment establishes 3-nitro as a central-peripheral neurotoxicant of pigs.     

Cataracts and optic nerve hypoplasia in turkey poults

Newly hatched commercial turkey poults culled because of grossly visible cataracts were studied. A total of 43 affected and 23 unaffected control poults at various ages were necropsied, and the ocular changes in affected poults were compared with those of aged-matched controls. Affected poults had consistent cataracts coupled with a marked depletion in retinal inner plexiform, ganglion cell, and optic nerve fiber layers, with a resultant reduction in the size of the optic nerves. Lesions were seen in 1-day-old poults. Lens changes included microphakia and lens fiber degeneration throughout the lens, with nuclear liquefaction. The depletion in the numbers of retinal ganglion cells did not appear to progress over several weeks time. The ganglion cell depletion was not uniform within the retina. The cause for these ocular changes is unknown.     

Insulinoma and Subclinical Peripheral Neuropathy in Two Dogs

Two dogs with diffuse, subclinical polyneuropathy associated with insulinoma are reported. Seizures were the dominant sign of central nervous system disease. One dog had clinical signs of facial nerve paralysis. Lesions in selected appendicular and cranial nerves included a mixture of demyelination, remyelination, and axonal degeneration. The incidence (range: 18-47%) of these changes far exceeded that of comparable nerves from six control dogs (range 0-11%). Myopathic and electrodiagnostic findings were compatible with the nerve changes.