MRI features of gliomatosis cerebri in a dog

The features of gliomatosis cerebri involving the brainstem and cerebellum in a 3-year-old dog are described. In magnetic resonance (MR) images, there was diffuse loss of the cerebellar folia and cerebellar gray and white matter contrast. Multiple illdefined T2-hyperintensities were present in the cerebellar parenchyma. A poorly defined, T2-hyperintense mass effect was present ventral to the pons and rostral medulla. No contrast enhancement was noted. Cerebrospinal fluid (CSF) was normal. Postmortem examination was consistent with gliomatosis cerebri, based on compatible histopathology and immunohistochemical findings. Although rare, gliomatosis cerebri should be included as a differential for diffuse infiltrative central nervous system (CNS) lesions.     

THREE TESLA MAGNETIC RESONANCE IMAGING FINDINGS IN 12 CASES OF CANINE CENTRAL EUROPEAN TICK‐BORNE MENINGOENCEPHALOMYELITIS

Central European tick‐borne encephalomyelitis can be challenging to diagnose in dogs because the virus may not be detected in blood and cerebrospinal fluid (CSF) after the first viremic stage of the disease. The purpose of this retrospective case series study was to describe 3 Tesla magnetic resonance imaging (3T MRI) findings in a sample of dogs with a confirmed diagnosis of tick‐borne encephalomyelitis. Dogs were included if they had neurological signs consistent with tick‐borne encephalomyelitis, history of a stay in endemic areas for tick‐borne encephalomyelitis virus, 3T MRI of the brain and/or spinal cord, cerebrospinal fluid changes compatible with viral infection and positive antibody titers in cerebrospinal fluid or pathologic confirmation of tick‐borne encephalomyelitis. Twelve dogs met inclusion criteria. Ten out of 12 patients had 3T MRI lesions at the time of presentation. One patient had persistent lesions in follow‐up MRI. The 3T MRI findings included bilateral and symmetrical gray matter distributed lesions involving the thalamus, hippocampus, brain stem, basal nuclei, and ventral horn on the spinal cord. All lesions were hyperintense in T2‐weighted sequences compared to white matter, iso‐ to hypointense in T1‐weighted, nonenhancing, and had minimal or no mass effect or perilesional edema. Six patients survived while the remaining six dogs were euthanized. Necropsy revealed neuronophagia and gliosis of the gray matter of the affected regions seen in 3T MRI, in addition to the cerebellum. Findings from the current study indicated that tick‐borne encephalomyelitis should be included in the differential diagnosis list for dogs with the above described 3T MRI characteristics.     

A morphological and stereological study on brain,cerebral hemispheres and cerebellum of New Zealand rabbits

The aim of this research was to determine brain, cerebral hemispheres and cerebellum volume and volume ratios by using stereological methods and investigate morphological differences between female and male New Zealand rabbits. The study was applied on 14-month old (10 male and 10 female) New Zealand rabbits. The materials removed from the cavum cranii using dorsal approach. After following routine histological procedure, paraffin blocks were prepared and cut every seventieth section at 10 μm thickness. Slides were stained with Crossmon's triple stain and photographed. The sectional images obtained were transferred to ImageJ program to estimate grey and white matter volume on cerebral hemispheres and cerebellum with principle of Cavalieri. According to results, there was no asymmetry on the left and right cerebral hemispheres of New Zealand rabbits. In the total hemisphere volume calculated by Cavalieri principle, grey and white matter ratio was 81.57% and 18.43% in female, 82.80% and 17.20% in male. It was found that the white matter was significantly higher in females than males in cerebral hemispheres (p < .05). Also, it was found that grey and white matter ratio in total cerebellum volume was 67.82% and 32.18% in female, 67.94% and 32.06% in male respectively. It was determined that the females' white matter was larger than male rabbits in cerebellum (p < .05). It is thought that morphometric data obtained from this study will contribute to the existing anatomical knowledge and also considered as reference values in the clinical sciences.     

Chiari‐like malformation in two cats

Two male, neutered, domestic, shorthaired cats were evaluated for progressive paresis and ataxia. Neurological examinations suggested a spinal cord lesion in each case. Complete blood examination and cerebrospinal fluid analysis were unremarkable in both cats. MRI revealed malformation of the occipital bone with herniation of the cerebellar vermis through the foramen magnum but without syringomyelia. Chiari‐like malformation was suspected in both patients. MRI repeated one year later in both cats because of progression of clinical signs yielded the same findings as the initial scans. Foramen magnum decompression in one cat was associated with resolution of clinical signs.     

An immunohistochemical and ultrastructural study on age-related astrocytic gliosis in the central nervous system of dogs.

The pattern of astrocytic gliosis (AG) was examined in 2-month-old to 18-year-old dogs using glial fibrillary acidic protein (GFAP) immunohistochemistry and electron microscopy. Coronal sections from various levels of the central nervous system (CNS) were stained with hematoxylin & eosin, Luxol Fast Blue, Nissl, and Bodian in addition to GFAP. A consistent pattern of age-related AG was observed in the dogs. The white matter, cortico-medullary junction, and subcortical nuclei in the cerebrum, central nuclei in the cerebellum, various nuclei in the brain stem, and grey matter of the spinal cord showed even and intense GFAP staining. AG was also prominent in the cerebral and cerebellar cortices and thalamus. Moderate AG was observed in the hippocampus and white matter of the cerebellum and spinal cord. Electron microscopy demonstrated increased number of profiles of degenerative neural components in the vicinity of hypertrophic astrocytes in the cerebral cortex of the aged dogs. Moderate to severe AG was consistently shown in the CNS of the aged dogs. In contrast, young normal dogs showed minimum amounts of GFAP-positive astrocytes in the CNS. These findings suggest that the observed AG in the CNS of the dogs is a morphological expression of aging.     

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.     

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.     

Eosinophilic meningomyelitis associated with T‐cell lymphoma in a cat

A 12‐year‐old cat was presented for evaluation of progressive tetraparesis. Magnetic resonance imaging of the cervical spine demonstrated T2‐hyperintensity, and contrast enhancement within the C4–C7 spinal cord, with marked meningeal contrast enhancement and segmental nerve root thickening. Lumbar cerebrospinal fluid contained 407 total nucleated cells/μL, with 99% eosinophils. The cat transiently improved with prednisolone, clindamycin, and ivermectin therapy, but subsequently worsened and was euthanized. Necropsy revealed an asymmetric infiltration predominantly of the white matter, meninges, and nerve roots of the C4–C6 spinal cord segments by an unencapsulated, poorly demarcated neoplasm composed of atypical lymphocytes admixed with eosinophils, causing perivascular hemorrhage and lytic necrosis. The neoplastic cells were immunoreactive for CD3, ultimately confirming T‐cell lymphoma.     

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.     

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.     

MAGNETIC RESONANCE IMAGING OF INTRACRANIAL INFLAMMATORY CONDITIONS IN DOGS: SENSITIVITY OF SUBTRACTION IMAGES VERSUS PRE‐ AND POST‐GADOLINIUM T1‐WEIGHTED IMAGE PAIRS

Ante mortem diagnosis of canine meningoencephalitis is usually based on the results of neurologic examination, cerebrospinal fluid analysis and magnetic resonance (MR) imaging. It has been hypothesized that subtraction MR imaging may increase the sensitivity of MR for intracranial inflammatory lesions compared to conventional post‐gadolinium T1‐weighted imaging. Sensitivity of pre‐ and post‐gadolinium (C‐/C+) image pairs and dynamic subtraction (DS) images was compared in a retrospective diagnostic accuracy study of 52 dogs with inflammatory cerebrospinal fluid and 67 dogs with idiopathic epilepsy. Series of transverse C‐/C+ and DS images were reviewed independently for signs of abnormal enhancement affecting the pachymeninges, leptomeninges or intra‐axial structures. Sensitivity of C‐/C+ image pairs and DS images was 48% (95% CI: 35–61%) and 65% (95% CI: 52–77%), respectively (P = 0.01). Intra‐axial lesions were observed more frequently than meningeal lesions in both C‐/C+ (43% vs. 31%) and DS images (61% vs. 22%). The difference in sensitivities of C‐/C+ and DS series was entirely due to increased sensitivity of DS images for intra‐axial lesions. Eight (12%) dogs with epilepsy had evidence of intra‐axial gadolinium accumulation affecting the cerebral cortex in DS images. This finding may represent a false‐positive result or a true sign of pathology, possibly associated with a leaky blood–brain barrier in areas of the brain affected by neovascularization secondary to repeated seizures. Results suggest that DS imaging has higher sensitivity than comparison of pre‐ and post‐gadolinium image pairs for inflammatory intra‐axial lesions.     

GM2 Gangliosidosis Variant 0 (Sandhoff‐Like Disease) in a Family of Toy Poodles

Background: GM2 gangliosidosis variant 0 (human Sandhoff disease) is a lysosomal storage disorder caused by deficiencies of acid β‐hexosaminidase (Hex) A and Hex B because of an abnormality of the β‐subunit, a common component in these enzyme molecules, which is coded by the HEXB gene. Objective: To describe the clinical, pathological, biochemical, and magnetic resonance imaging (MRI) findings of Sandhoff‐like disease identified in a family of Toy Poodles. Animals: Three red‐haired Toy Poodles demonstrated clinical signs including motor disorders and tremor starting between 9 and 12 months of age. The animals finally died of neurological deterioration between 18 and 23 months of age. There were some lymphocytes with abnormal cytoplasmic vacuoles detected. Methods: Observational case study. Results: The common MRI finding was diffuse T2‐hyperintensity of the subcortical white matter in the cerebrum. Bilateral T2‐hyperintensity and T1‐hypointensity in the nucleus caudatus, and atrophic findings of the cerebrum and cerebellum, were observed in a dog in the late stage. Histopathologically, swollen neurons with pale to eosinophilic granular materials in the cytoplasm were observed throughout the central nervous system. Biochemically, GM2 ganglioside had accumulated in the brain, and Hex A and Hex B were deficient in the brain and liver. Pedigree analysis demonstrated that the 3 affected dogs were from the same family line. Conclusions and Clinical Importance: The Sandhoff‐like disease observed in this family of Toy Poodles is the 2nd occurrence of the canine form of this disease and the 1st report of its identification in a family of dogs.     

Ataxia and weakness as uncommon primary manifestations of hepatic encephalopathy in a 15‐year‐old trotter gelding

A 15‐year‐old trotter gelding was evaluated because of an acute onset of ataxia in all 4 limbs. There was no known history of trauma. The gelding showed grade 2/5 ataxia in all 4 limbs, which was localised after clinical neurological examination to the cervical vertebral spinal cord. Initial therapy consisted of oral anti‐inflammatory doses of prednisolone and antimicrobial treatment with potentiated sulphonamides. The ataxia progressed to grade 3/5 at Day 10 of hospitalisation. Additionally, the horse was slightly depressed and showed spontaneous yawning during examination. Facial sensation was blunted. Blood chemistry revealed a marked elevation of liver specific enzymes and blood ammonia levels. Transcutaneous abdominal ultrasonography revealed hepatomegaly. Due to a guarded prognosis, the horse was subjected to euthanasia. At necropsy the left lateral liver lobe was markedly enlarged and showed a firm texture, whereas the cranial part and the right and quadratic liver lobe displayed a severe and diffuse atrophy. Histopathologically, the left lateral liver lobe revealed a moderate to severe cirrhosis with a severe, diffuse hepatocellular iron‐accumulation. Increased numbers of Alzheimer type II astrocytes in the cerebral cortex and cerebral white matter vacuolisation were indicative for encephalopathy. These findings were interpreted as haemosiderosis and cirrhosis of the liver with consecutive hepatic encephalopathy. Aetiologically, haemosiderosis should be considered as a cause of liver cirrhosis with consecutive hepatic encephalopathy. Although hepatic encephalopathy in horses usually presents with predominating cerebral signs, it has to be taken into account as a differential diagnosis in cases of acute onset generalised ataxia.     

Experimentally induced thiamine deficiency in beagle dogs: pathologic changes of the central nervous system

Brain and spinal cord were examined in twenty-two 2- to 5-month-old Beagle dogs fed a purified thiamine-deficient ration for 84 +/- 42 (range, 32 to 134) days. Eleven dogs were used as principals, 6 were pair-fed controls, and 5 were controls fed ad libitum. Thiamine at 300 micrograms/kg of body weight was administered IM to control groups once a week. Lesions occurred in 2 topographic patterns in the brain of 8 of the principals. In pattern I, only the caudal colliculi were involved. In pattern II, the suprasplenial gyri of the cerebral cortex and the claustra, caudal colliculi, cerebellar nodulus, and medial vestibular nuclei were commonly involved. In both patterns I and II, gray matter was primarily involved, and in bilateral structures, the 2 sides were affected. Lesions were not limited to a given cerebral lamina or layer of the cerebellum, whereas sulcal areas were relatively spared, and the cingulate gyri were completely spared. Microscopic appearance of the lesions varied greatly among locations and individual principals. Collectively, regressive and reparative changes indicated that there was a progressive process which began with spongiosis and ended with tissue necrosis. These included hydropic vacuolation of the neuropil and myelin sheaths followed by demyelination, neuronal cell body necrosis, hypertrophy and hyperplasia of endothelial cells, necrosis of glia, neutrophil infiltration, disintegration of neuropil, and, finally, accumulation of lipid-containing phagocytes. Axonal degeneration was variable. Neuronal necrosis in the brain stem was characterized by acute swelling and lysis and by shrinkage of the cell body in cerebral and cerebellar cortex and basal ganglia.     

Unusual manifestation of hepatic encephalopathy in two Irish wolfhound siblings

In hepatic encephalopathy the brain lesions are usually characterised by polymicrocavitation, preferentially in the white matter, and the occurrence of Alzheimer type II cells. This paper describes an unusual manifestation of hepatic encephalopathy in two Irish wolfhound siblings in which the white matter was not involved predominantly. Both puppies had developed progressive neurological disturbances and signs of blindness. Histologically, there were widespread spongiform changes in the neuropil and fibre bundles interspersed within the grey matter, and there were some neuronal vacuoles. In both animals, the regions of the brain mainly affected were the nucleus caudatus, amygdala, cerebellar nuclei, mesencephalon, thalamus, hypothalamus and medulla oblongata. An astrogliosis characterised by Alzheimer type II-like cells was also observed. Electron microscopy revealed a splitting of the myelin sheath. No infectious agents such as rabies virus, canine distemper virus or prion proteins were detected. The main findings in the portal regions of the liver consisted of a dilatation of the lymphatic vessels and increased numbers of small arteries, indicating that a portosystemic shunt was the probable cause of the spongiform brain lesions.     

Spongy degeneration of white matter in the central nervous system of silver foxes (Vulpes vulpes)

A disorder of central nervous white matter in Norwegian-bred silver foxes is described from the case histories of 21 clinically affected foxes. The main presenting sign of this disorder was caudal limb ataxia, which appeared between 2 1/2 and 4 months of age and progressed over the next 4-8 weeks. Only four affected foxes were allowed to live beyond this period, but they showed moderate to marked improvement. Light microscopic examination of specimens from 16 affected foxes necropsied between 3 1/2 and 6 1/2 months of age revealed lesions that were restricted to the white matter of brain and spinal cord. The lesions were characterized by a symmetrical spongy change with vacuoles of varying sizes and included significant myelin deficiency. There was a relative preservation of axons and nerve cells and no significant inflammation or vascular reaction. An astrocytic hypertrophy was usually associated with the spongy change. Ultrastructural examination of central nervous tissue from two, perfusion-fixed, 6-month-old foxes showed intramyelin vacuoles resulting from splitting of the myelin lamellae at the intraperiod line and was interpreted as indicating myelin edema. Expanded extracellular spaces and watery astrocytic processes also contributed to the vacuolar appearance. Astrocytic processes in affected areas were hypertrophic and contained abundant filaments. Although the 16 silver foxes had severe clinical signs, their lesions had features in common with the juvenile form of Canavan's disease in children and a spongy degeneration reported in Labrador Retrievers; however, the clinical course in the foxes was not uniformly progressive.     

Hexachlorophene and cuprizone induce the spongy change of the developing rat brain by different mechanisms: the role of 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)

The goal of this research was to identify mechanisms responsible for the spongy change induced in rats after repeated hexachlorophene (HCP) or cuprizone (CPZ) dosing. Rats were dosed with 35 mg/kg HCP for 5 days followed by drug withdrawal for 7 days suffered spongy changes to the white matter of the cerebrum, cerebellum, medulla oblongata, and spinal cord that were accompanied by degeneration of oligodendroglia. The severity of both lesions increased prominently on day 5; however, the spongy change decreased and degeneration of oligodendroglia reversed on day 12 (7 days after dosing ceased). On day 12, cerebral cortex oligodendroglia were stained strongly by anti-CNPase. Other rats were fed for 8 days with powdered chow containing 1% (w/w) CPZ, which was then withdrawn for 16 days. The rats exhibited the spongy change in the white matter of the cerebrum and cerebellum as well as oligodendroglial cell death from day 3. The severity of both lesions increased prominently on day 8. Cerebral cortex oligodendroglia were stained strongly by anti-CNPase on days 3 to 8 and decreased to the control levels by day 24 (16 days after dosing ceased). Electron microscopy revealed that oligodendroglia frequently displayed apoptotic morphology. These findings suggest that CNPase expression was induced in the course of restoration following HCP-induced insults to oligodendroglia and the myelin sheath, and in the course of demyelination by CPZ-induced damage to oligodendroglia. However, the role of CNPase on both courses is unclear.     

Three‐dimensional T1‐weighted gradient echo is a suitable alternative to two‐dimensional T1‐weighted spin echo for imaging the canine brain

Volumetric imaging (VOL), a three‐dimensional magnetic resonance imaging (MRI) technique, has been described in the literature for evaluation of the human brain. It offers several advantages over conventional two‐dimensional (2D) spin echo (SE), allowing rapid, whole‐brain, isotropic imaging with submillimeter voxels. This retrospective, observational study compares the use of 2D T1‐weighted SE (T1W SE), with T1W VOL, for the evaluation of dogs with clinical signs of intracranial disease. Brain MRI images from 160 dogs who had T1W SE and T1W VOL sequences acquired pre‐ and postcontrast, were reviewed for presence and characteristics of intracranial lesions. Twenty‐nine of 160 patients were found to have intracranial lesions, all visible on both sequences. Significantly better grey‐white matter (GWM) differentiation was identified with T1W VOL (P < .001), with fair agreement between the two sequences (weighted κ = 0.35). Excluding a mild reduction in lesion intensity in three dogs precontrast on the T1W VOL images compared to T1W SE, and meningeal enhancement noted on the T1W VOL images in one dog, not identified on T1W SE, there was otherwise complete agreement between the two sequences. The T1W VOL sequence provided equivalent lesion evaluation and significantly improved GWM differentiation. Images acquired were of comparable diagnostic quality to those produced using a conventional T1W SE technique, for assessment of lesion appearance, number, location, mass effect, and postcontrast enhancement. T1W VOL, therefore, provides a suitable alternative T1W sequence for canine brain evaluation and can facilitate a reduction in total image acquisition time.