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.     

An autosomal recessive, lethal, neurologic disease of Gordon Setter puppies.

This report details clinical, necropsy, and pedigree data on an inherited, lethal, neurologic disease of young Gordon Setters. This disorder is characterized by an early age of onset, gait and postural abnormalities, progressive weakness, and recumbency by 5-6 weeks of age. Although clinically distinctive, postmortem changes in affected pups were minimal. Gross lesions were not observed. Microscopic changes were subtle and consisted of astrocyte swelling, primarily in the cerebrocortical and cerebellar white matter, and white matter tracts of the brainstem. Immunohistochemistry for glial fibrillary acidic protein revealed a marked increase in the number and staining intensity of astrocyte cytoplasmic processes in affected pups compared with age-matched controls. Neither cerebral inflammation nor neuronal necrosis was identified. Pedigree analysis of affected litters demonstrated an autosomal recessive mode of inheritance. A diagnosis of this heritable disease should be based on the early age of onset (3-4 weeks of age), characteristic clinical signs, rapid progression to recumbency by 5-6 weeks of age, identification of swollen astrocytes primarily in the cerebellar and cerebrocortical white matter and white matter tracts of the brainstem, and the exclusion of other disease processes.     

Assessment of the neurologic effects of dietary deficiencies of phenylalanine and tyrosine in cats

OBJECTIVE: To determine the neurologic effects of reduced intake of phenylalanine and tyrosine in black-haired cats. ANIMALS: 53 specific pathogen-free black domestic shorthair cats. PROCEDURE: Cats were fed purified diets containing various concentrations of phenylalanine and tyrosine for < or = 9 months. Blood samples were obtained every 2 months for evaluation of serum aromatic amino acid concentrations. Cats were monitored for changes in hair color and neurologic or behavioral abnormalities. Three cats with neurologic deficits underwent clinical and electrophysiologic investigation; muscle and nerve biopsy specimens were also obtained from these cats. RESULTS: After 6 months, neurologic and behavioral abnormalities including vocalization and abnormal posture and gait were observed in cats that had received diets containing < 16 g of total aromatic amino acid/kg of diet. Electrophysiologic data and results of microscopic examination of muscle and nerve biopsy specimens from 3 cats with neurologic signs were consistent with sensory neuropathy with primary axonal degeneration. Changes in hair color were detected in cats from all groups receiving < 16 g of phenylalanine plus tyrosine/kg of diet. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggested that chronic dietary restriction of phenylalanine and tyrosine in cats may result in a predominantly sensory neuropathy. In cats, the long-term nutritional requirement for phenylalanine and tyrosine appears to be greater for normal neurologic function than that required in short-term growth experiments. Official present-day recommendations for dietary phenylalanine and tyrosine in cats may be insufficient to support normal long-term neurologic function.     

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.     

Cerebellar cortical degeneration in three English bulldogs: clinical and neuropathological findings

This case report describes the clinical and neuropathological findings in three young English bulldogs affected by cerebellar cortical degeneration. The dogs, born from the same parents, were presented with clinical signs indicating progressive cerebellar dysfunction: a wide-based stance, severe cerebellar ataxia characterised by marked hypermetria, spasticity, and intention tremors of the head and trunk with loss of balance. On histopathological examination, lesions were confined to the cerebellum and consisted of diffuse degenerative cortical lesions, and there was a loss of Purkinje and granule cells. The history, clinical signs and neuropathological findings confirmed the diagnosis of cerebellar cortical degeneration. To the authors' knowledge, this is the first report of cerebellar cortical degeneration in the English bulldog.     

Cerebellar degeneration in a mature Staffordshire terrier

A 5-year-old Staffordshire terrier exhibited slowly progressive signs of cerebellar disease, including nystagmus and dysmetria. After a 30-month course, the dog was euthanized. Grossly, the cerebellum was small and comprised only 5% of the brain weight. Histopathological examination of the brain documented diffuse degeneration. Purkinje cells were most depleted, but granular cells and the molecular layer of cerebellum were also depleted. The history and necropsy examination were evidence of late-onset primary cerebellar degeneration.     

Cerebellar cortical abiotrophy in American Staffordshire terriers: clinical and pathological description of 3 cases

Three American Staffordshire Terriers were presented with gait abnormalities and loss of balance at the age of 4.5 (female) and 6 years (2 males). The onset varied between 3 and 5 years of age and the clinical signs were slowly progressive. The neurological examination revealed symmetrical generalized cerebellar ataxia with hypermetria, stiffness, and loss of balance with no evidence of paresis. The menace reflex was decreased in one dog and absent in another. A positional nystagmus was found in two dogs. The dogs were euthanized and a histopathological examination of each brain was performed. Pathological changes were confined to the cerebellum. The main finding was loss of Purkinje cells, as well as depletion of granular cell bodies and shrinkage of the granular and molecular cell layer. These findings are consistent with cerebellar cortical abiotrophy. A genetic basis is supposed, but the mode of inheritance is not determined yet. In contrast to some spinocerebellar ataxias in humans, the cause of Purkinje cell degeneration in cerebellar cortical abiotrophy of dogs is not known.     

Neurologic disease putatively associated with ingestion of Solanum viarum in goats

Several Nubian-cross goats were evaluated because of chronic progressive neurologic disease. Physical and neurologic examination revealed signs consistent with diffuse cerebellar disease. Neurologic signs included generalized hyperresponsiveness, fine head tremors, wide-based posture, dysmetria, weakness, and horizontal nystagmus. No clinical improvement was noted after removing goats from affected enclosures. Histologic examination of cerebellar tissues revealed extensive vacuolation within the cytoplasm of Purkinje cells. The clinical and histologic lesions resembled closely findings that were associated with ingestion of Solanum spp in cattle and goats. Examination of enclosures revealed Solanum viarum (tropical soda apple) that had been heavily consumed by the goat herd. We hypothesized that ingestion of S. viarum caused the neurologic disorder.     

Cerebellar hypoplasia in three sibling cats after intrauterine or early postnatal parvovirus infection

The present report describes the case of an intrauterine or early postnatal parvovirus infection with subsequent cerebellar hypoplasia in three kittens from the same litter. Clinical examination of affected cats revealed neurologic signs indicative of cerebellar ataxia. Due to poor prognosis, animals were euthanised and submitted for necropsy. Post mortem examination demonstrated variable degrees of cerebellar hypoplasia. Histologically, brain lesions were characterised by segmental loss of the external and internal granular layer and decreased numbers of Purkinje cells. Reactive proliferation of astrocytes in the central nervous system was verified by the detection of GFAP-expressing glial cells in affected areas using immunohistochemistry. Furthermore, parvovirus antigen was detected immunohistochemically in neuronal cells of the cerebellum, but not in other parts of the brain and spinal cord or non-neuronal tissues. The present report demonstrates the usefulness of post mortem examination and detection of viral antigen by immunohistochemistry for the discrimination of neurologic disorders in feline species. Neurologic deficiencies due to cerebellar hypoplasia caused by in utero or perinatal feline parvovirus infection should be taken into consideration as differential diagnoses for ataxia in neonatal and juvenile cats.     

Cerebellar cortical degeneration with selective granule cell loss in Bavarian mountain dogs

Three Bavarian mountain dogs aged between 18 and 20 months, not related to each other, were presented with chronic signs of cerebellar dysfunction. On sagittal T2-weighted magnetic resonance imaging brain images, the tentative diagnosis of cerebellar hypoplasia was established based on an enlarged cerebrospinal fluid space around the cerebellum and an increased cerebrospinal fluid signal between the folia. Post-mortem examination was performed in one dog and did show an overall reduction of cerebellar size. On histopathologic examination, a selective loss of cerebellar granule cells with sparing of Purkinje cells was evident. Therefore, the Bavarian mountain dog is a breed where cerebellar cortical degeneration caused by the rather exceptional selective granule cell loss can be seen as cause of chronic, slowly progressive cerebellar dysfunction starting at an age of several months.     

Nature and cause of bilateral ocular dermoids in Hereford cattle

Nature and cause of bilateral ocular dermoids were investigated by field studies, pedigree analysis, clinical examination, light microscopy, scanning electron microscopy, and transmission electron microscopy. It was determined that ocular dermoids in Hereford cattle are a genetically transmitted defect; characteristics of autosomal recessive and polygenic inheritance were observed. Calves typically were affected bilaterally with multiple, connected ocular growths that clinically, histologically, and ultrastructurally mimicked normal haired skin. Sites most commonly involved included ventro-lateral limbus, third eyelid, medial canthus, eyelid and conjunctiva. Centro-corneal and anterior segmental dermoids also were observed.     

Long-term survival after surgical excision of a schwannoma of the sixth cervical spinal nerve in a dog

A schwannoma of the sixth cervical spinal nerve in a 5-year-old Shetland Sheepdog was surgically excised, sparing the thoracic limb and resulting in long-term survival. The dog had been referred because of slowly progressive left thoracic limb lameness. The lesion was localized to the left suprascapular and musculocutaneous nerves or the C6 and C7 spinal nerves on the basis of neurologic examination, electrodiagnostic examination, and myelography. Surgical exploration revealed a mass, which was excised and identified histologically as a schwannoma. Three and a half years later, the dog was normal except for mild gait abnormality, focal muscle atrophy, and a focal area of decreased cutaneous sensation of the left thoracic limb.     

Diagnostic implications of detection of proteinase K-resistant protein in spleen, lymph nodes, and brain of sheep.

Brain, spleen, and selected lymph nodes from sheep with clinical signs of scrapie were analyzed for presence of proteinase K-resistant protein (PrP-res). Diagnosis of scrapie on the basis of detection of PrP-res was compared with diagnosis on the basis of histologic evaluation of the brain from clinically affected or exposed sheep. Proteinase K-resistant protein was found in every brain that was histologically positive for scrapie, and in addition, was found in the brain of several clinically positive sheep that were not diagnosed as scrapie-positive by histologic evaluation. Proteinase K-resistant protein was also found in 87% of the spleens and lymph nodes from sheep that had PrP-res detected in brain homogenates. Therefore, analysis of sheep brain, spleen, or lymph nodes for PrP-res provided a diagnostic approach that was superior to histologic examination alone for detection of naturally scrapie agent-infected sheep.     

Pentobarbital poisoning in Sumatran tigers (Panthera tigris sumatrae).

Three Sumatran tigers (Panthera tigris sumatrae) at the Heidelberg Zoo in Germany presented with severe neurologic signs. Physical examination and diagnostic tests did not reveal a definitive diagnosis. Two days after initial presenting signs, all of the animals appeared clinically normal. An investigation into this outbreak revealed that all animals received horse meat on the evening before the incident. A toxicologic examination was initiated and serum analysis of the affected female tiger cub and the horse meat revealed contamination with pentobarbital.     

Association between neurologic and cognitive dysfunction signs in a sample of aging dogs

In human neurology, patients with Alzheimer's disease show seizures and signs of motor deficits, such as movement disorders (i.e., restlessness, slowness, impaired gait, and, rarely, resting tremors). Because canine Cognitive Dysfunction Syndrome (CDS) is considered an Alzheimer-like disease in dogs, it might be possible to document concurrent behavioral and neurologic signs in aging canine patients as well. Twenty-one dogs (14 dogs with CDS-related signs, 7 normal dogs) greater than 7 years of age were studied. Owners completed a behavioral questionnaire and the dogs underwent a neurologic evaluation. Dogs with CDS were twice as likely to show neurologic deficits as dogs without CDS. However, based on this pilot study, a sample of 187 dogs affected with CDS are required to show statistically significant differences between the proportions of dogs with CDS and with neurologic signs and the proportions of control dogs without any of these disorders.     

Cerebellar granuloprival degeneration in an Italian hound

A severe atrophy of the cerebellum was observed in a 7-month-old male Italian hound with a history of progressive ataxia and head tremor from the age of 3 months. On clinical examination, signs included severe hypermetric gait, head tremors and proprioception deficits in all limbs. At necropsy, a pronounced symmetrical reduction in size of the cerebellum was the only gross lesion observed. Histological examination of the cerebellum revealed marked thinning of the granular and molecular layers with almost complete loss of granule cells. Purkinje cells had normal morphology and distribution. These findings differ from those of previous reports of cerebellar cortical abiotrophy in dogs, which were mainly characterized by prominent Purkinje cell degeneration and loss.     

Myelopathy and vitamin E deficiency in six Mongolian wild horses

Degenerative myelopathy was diagnosed in six Mongolian wild horses. Three of the horses had a history of ataxia dating from birth to 3 months of age. The clinical signs were uncoordinated movement of the hindlimbs and an abnormally wide-based gait and stance. The other 3 horses had mild ataxia. There were no gross lesions in the brain, vertebrae, or spinal cord. Histologic examination revealed degeneration of the neural processes in the ventral and lateral funiculi of all 6 horses. Myelin sheaths were dilated and vacuolated, and there were swollen, fragmented, or lysed axons. Neuronal degeneration, phagocytosis, and accumulation of periodic acid-Schiff-positive, xylol-insoluble lipopigment were observed in the affected neurons of the dorsal root ganglia. The plasma alpha-tocopherol values of 5 of the affected horses ranged from less than 0.03 to 0.08 (mean, 0.04 +/- 0.01) mg/dl. Seven clinically normal horses from the same herd had a range of less than 0.03 to 0.3 (mean, 0.11 +/- 0.02) mg/dl, which was low enough to be considered deficient.     

A neurologic syndrome in Golden Retrievers presenting as a sensory ataxic neuropathy

BACKGROUND: A sensory ataxic neuropathy has been observed in Swedish Golden Retrievers recently. ANIMALS: Twenty-one affected Golden Retrievers. METHODS: Clinical and neurologic status, electrophysiologic, and pathologic status as well as pedigree analyses were evaluated. RESULTS: Clinical signs had an insidious onset between 2 and 8 months of age and a slowly progressive course. Affected dogs were ataxic and dysmetric. They had abnormal postural reactions and decreased spinal reflexes but no apparent muscle atrophy. Clinical pathology, radiography, and electrophysiology of motor systems were all within reference values. Sensory nerve conduction results of affected dogs were significantly different from those of a group of control dogs. Necropsy revealed a chronic progressive central and peripheral sensorimotor axonopathy; the proprioceptive pathways were most severely affected. CONCLUSIONS AND CLINICAL IMPORTANCE: This disease in these Golden Retrievers is distinct from other canine breed-related neurodegenerative diseases or hereditary neurodegenerative diseases described in humans. Pedigree analyses indicated a hereditary background, but the mode of inheritance could not be established.