Elsa Beltran

Genome-wide mRNA sequencing of a single canine cerebellar cortical degeneration case leads to the identification of a disease associated SPTBN2 mutation

BackgroundNeonatal cerebellar cortical degeneration is a neurodegenerative disease described in several canine breeds including the Beagle. Affected Beagles are unable to ambulate normally from the onset of walking and the main pathological findings include Purkinje cell loss with swollen dendritic processes. Previous reports suggest an autosomal recessive mode of inheritance. The development of massively parallel sequencing techniques has presented the opportunity to investigate individual clinical cases using genome-wide sequencing approaches. We used genome-wide mRNA sequencing (mRNA-seq) of cerebellum tissue from a single Beagle with neonatal cerebellar cortical degeneration as a method of candidate gene sequencing, with the aim of identifying the causal mutation.ResultsA four-week old Beagle dog presented with progressive signs of cerebellar ataxia and the owner elected euthanasia. Histopathology revealed findings consistent with cerebellar cortical degeneration. Genome-wide mRNA sequencing (mRNA-seq) of RNA from cerebellum tissue was used as a method of candidate gene sequencing. After analysis of the canine orthologues of human spinocerebellar ataxia associated genes, we identified a homozygous 8 bp deletion in the β-III spectrin gene, SPTBN2, associated with spinocerebellar type 5 in humans. Genotype analysis of the sire, dam, ten clinically unaffected siblings, and an affected sibling from a previous litter, showed the mutation to fully segregate with the disorder. Previous studies have shown that β-III spectrin is critical for Purkinje cell development, and the absence of this protein can lead to cell damage through excitotoxicity, consistent with the observed Purkinje cell loss, degeneration of dendritic processes and associated neurological dysfunction in this Beagle.ConclusionsAn 8 bp deletion in the SPTBN2 gene encoding β-III spectrin is associated with neonatal cerebellar cortical degeneration in Beagle dogs. This study shows that mRNA-seq is a feasible method of screening candidate genes for mutations associated with rare diseases when a suitable tissue resource is available.

Clinical and magnetic resonance imaging features of canine compressive cervical myelopathy with suspected hydrated nucleus pulposus extrusion

OBJECTIVE To describe clinical and magnetic resonance imaging features in dogs with compressive cervical myelopathy due to acute suspected hydrated nucleus pulposus extrusion. DESIGN Retrospective case series. ANIMALS Ten dogs with compressive cervical myelopathy caused by acute suspected hydrated nucleus pulposus extrusion. MATERIALS AND METHODS Medical records and magnetic resonance images of dogs evaluated from 2005 through 2010 were reviewed. The inclusion criteria were clinical signs compatible with cervical myelopathy, magnetic resonance imaging of the spine performed within 48 hours after onset, magnetic resonance imaging findings consistent with compressive suspected hydrated nucleus pulposus extrusion, complete medical records and follow-up information. RESULTS Six dogs were presented with acute onset tetraplegia and four dogs with acute onset of nonambulatory tetraparesis. Compromised respiratory function was present in three dogs. Compressive suspected hydrated nucleus pulposus extrusion was found on magnetic resonance imaging at the C4-C5 (n=6), C3-C4 (n=3) and C5-C6 (n=1) intervertebral disc spaces. Seven dogs underwent surgical treatment and three dogs were treated conservatively. All dogs except one regained ambulatory status within two weeks after the onset, and had a favourable outcome. CLINICAL SIGNIFICANCE Compressive myelopathy caused by acute suspected hydrated nucleus pulposus extrusion has not been reported previously and, even though neurological deficits can be severe on presentation, outcome is favourable.

Clinical Course of Acute Canine Polyradiculoneuritis Following Treatment with Human IV Immunoglobulin

Treatment of dogs with acute canine polyradiculoneuritis (ACP) is restricted to physical rehabilitation and supportive care. In humans with Guillain-Barré syndrome, the counterpart of ACP, randomized trials show that IV immunoglobulin (IVIg) speeds recovery. The authors of the current study hypothesized that dogs with ACP would tolerate IVIg well and recover faster than dogs managed with supportive treatment only. Sixteen client-owned dogs with ACP were treated with IVIg, and 14 client-owned dogs served as a retrospective control group. Diagnosis was confirmed using clinical features, electrodiagnostics, cerebrospinal fluid analysis, and muscle/nerve biopsies. The duration of the initial progressive phase, the time from IVIg administration until the dogs were ambulating without assistance, and the duration of the complete episode were evaluated. Adverse reactions (anaphylaxis, mild hematuria) were observed in two dogs. Dogs treated with IVIg were ambulating without assistance after a median of 27.5 days (range, 15-127 days) from onset of clinical signs. The control group was ambulatory without assistance at a median of 75.5 days (range, 5-220 days). Even though this result is not statistically significant, there is a clear trend toward faster recovery in dogs treated with IVIg.

MAGNETIC RESONANCE IMAGING CHARACTERISTICS OF SUSPECTED VERTEBRAL INSTABILITY ASSOCIATED WITH FRACTURE OR SUBLUXATION IN ELEVEN DOGS

The purpose of this study was to describe the magnetic resonance imaging (MRI) characteristics of suspected instability in dogs with vertebral fractures or subluxations. Eleven dogs that had MRI examinations of the spine prior to surgical stabilization of vertebral fractures and/or subluxations were included in the study. Nine dogs also had survey radiographs. Four dogs had cervical fracture or fracture-subluxation and presented with tetraplegia with intact nociception (n = 2) or nonambulatory tetraparesis (n = 2). Seven dogs had thoracolumbar fracture-subluxation or subluxation and presented with paraplegia with intact nociception (n = 5) or nonambulatory paraparesis (n = 2). A three-compartment model was applied to the interpretation of both the radiographic and MRI studies. Radiography identified compartmental disruption consistent with spinal instability in seven out of the nine cases radiographed. In MRI studies, rupture of the supportive soft tissue structures and/or fracture in at least two compartments could be visualized. Nine cases had spinal cord changes on MRI including signal intensity changes, swelling, compression, and intramedullary hemorrhage. Paravertebral muscle intensity changes were also visible at each trauma site. Magnetic resonance imaging provided helpful information on the location and extent of damage to supportive soft tissue structures and enabled assessment of spinal cord injury in this group of dogs with surgically confirmed vertebral fractures and subluxations.

Prognostic Value of Early Magnetic Resonance Imaging in Dogs after Traumatic Brain Injury: 50 Cases

Background The prognostic value of early magnetic resonance imaging (MRI) in dogs after traumatic brain injury (TBI) remains unclear. Objectives Determine whether MRI findings are associated with prognosis after TBI in dogs. Animals Fifty client‐owned dogs. Methods Retrospective study of dogs with TBI that underwent 1.5T MRI within 14 days after head trauma. MRI evaluators were blinded to the clinical presentation, and all images were scored based on an MRI grading system (Grade I [normal brain parenchyma] to Grade VI [bilateral lesions affecting the brainstem with or without any lesions of lesser grade]). Skull fractures, percentage of intraparenchymal lesions, degree of midline shift, and type of brain herniation were evaluated. MGCS was assessed at presentation. The presence of seizures was recorded. Outcome was assessed at 48 h (alive or dead) and at 3, 6, 12, and 24 months after TBI. Results Sixty‐six percent of the dogs had abnormal MRI findings. MRI grade was negatively correlated (P < .001) with MGCS. A significant negative correlation of MRI grade, degree of midline shift, and percentage of intraparenchymal lesions with follow‐up scores was identified. The MGCS was lower in dogs with brain herniation (P = .0191). Follow‐up scores were significantly lower in dogs that had brain herniation or skull fractures. The possibility of having seizures was associated with higher percentage of intraparenchymal lesions (P = 0.0054) and 10% developed PTE. Conclusions and Clinical Importance Significant associations exist between MRI findings and prognosis in dogs with TBI. MRI can help to predict prognosis in dogs with TBI.

Neurological dysfunction and caudal fossa overcrowding in a young cheetah with hypovitaminosis A.

HYPOVITAMINOSIS A has been reported to alter osteoblastic and osteoclastic activity in young animals, resulting in defective remodelling of cranial membranous bones, particularly the occipital and sphenoid bones, with subsequent caudal fossa overcrowding and herniation of the cerebellar vermis into

Dystrophin-deficient muscular dystrophy in a Norfolk terrier

A six-month-old male entire Norfolk terrier was presented with a 3-month history of poor development, reluctance to exercise and progressive and diffuse muscle atrophy. Serum creatine kinase concentration was markedly elevated. Magnetic resonance imaging of the epaxial muscles revealed asymmetrical streaky signal changes aligned within the muscle fibres (hyperintense on T2-weighted images and short-tau inversion recovery with moderate contrast enhancement on T1-weighted images). Electromyography revealed pseudomyotonic discharges and fibrillation potentials localised at the level of the supraspinatus, epaxial muscles and tibial cranialis muscles. Muscle biopsy results were consistent with dystrophin-deficient muscular dystrophy. The dog remained stable 7 months after diagnosis with coenzyme Q10 and l-carnitine; however after that time, there was a marked deterioration and the owners elected euthanasia. This case report describes the clinical presentation, magnetic resonance imaging, electrodiagnostic and histopathological findings with immunohistochemical analysis in a Norfolk terrier with confirmed dystrophin-deficient muscular dystrophy, which has not been previously described in this breed.

Expression of MMP-2 and MMP-9 in Benign Canine Rostrotentorial Meningiomas Is Not Correlated to the Extent of Peritumoral Edema

Matrix metalloproteinases (MMPs) are proteolytic enzymes involved with extracellular matrix degradation. They have been considered to be important for tumor growth and development of peritumoral edema. This retrospective study investigated the expression of MMP subtypes 9 and 2 in canine intracranial meningiomas and their association with peritumoral edema. Twenty-two cases of histologically confirmed grade I meningiomas based on human World Health Organization classification were enrolled. Tumor volume and peritumoral edema were measured by magnetic resonance imaging volumetry. The intratumoral MMP expression was semiquantitatively assessed by immunoreactivity scores and compared with the imaging data. MMP-9 was expressed in all the samples (22/22), whereas proMMP-2 was expressed in 21 of 22 meningiomas, and a/proMMP-2 was expressed in 9 of 22. The immunoreactivity scores were not statistically linked to the severity of peritumoral edema. None of the evaluated MMP expression parameters were statistically linked to the edema index. Although both edema index and MMP-9 expression were highest in meningiomas of the olfactory and frontal region, only the latter mounted up to statistical significance (P = .002) if compared with parafalx and convexity meningiomas of the parietal lobe. In summary, MMP-2 and MMP-9 expression by tumor cells, evaluated through immunohistochemistry, is not predictive of the formation of peritumoral edema in canine rostrotentorial meningiomas.

Cervical Vertebral Stenosis Associated with a Vertebral Arch Anomaly in the Basset Hound

OBJECTIVES To report the clinical presentation, imaging characteristics, treatment results, and histopathological findings of a previously undescribed vertebral malformation in the Basset Hound. ANIMALS AND METHODS Retrospective case series study. Eighteen Basset Hounds presented for evaluation of a suspected cervical spinal cord problem. All dogs underwent computed tomography myelography or magnetic resonance imaging of the cervical region. RESULTS Thirteen male and 5 female Basset Hounds between 6 months and 10.8 years of age (median: 1.4 years) were studied. Clinical signs varied from cervical hyperesthesia to nonambulatory tetraparesis. Imaging demonstrated a well-defined and smooth hypertrophy of the dorsal lamina and spinous process of ≥ 2 adjacent vertebrae. Although this bony abnormality could decrease the ventrodorsal vertebral canal diameter, dorsal midline spinal cord compression was predominantly caused by ligamentum flavum hypertrophy. The articulation between C4 and C5 was most commonly affected. Three dogs were lost to follow-up, 10 dogs underwent dorsal laminectomy, and medical management was initiated in 5 dogs. Surgery resulted in a good outcome with short hospitalization times (median: 4.5 days) in all dogs, whereas medical management produced more variable results. Histopathology confirmed ligamentum flavum hypertrophy and demonstrated the fibrocartilaginous nature of this anomaly. CONCLUSIONS AND CLINICAL IMPORTANCE Dorsal lamina and spinous process hypertrophy leading to ligamentum flavum hypertrophy should be included in the differential diagnosis of Basset Hounds with cervical hyperesthesia or myelopathy. Prognosis after decompressive surgery is favorable. Although a genetic component is suspected, additional studies are needed to determine the specific etiology of this disorder.

IMAGING DIAGNOSIS: PITUITARY APOPLEXY IN A CAT

A 7-year-old male neutered domestic short-haired cat had depression for 5 months and acute blindness. A lesion at the level of the rostral and middle cranial fossae was suspected. A large pituitary mass compressing the optic chiasm was detected in magnetic resonance images and there was also evidence of recent intratumoral hemorrhage, leading to a diagnosis of pituitary apoplexy; these findings were confirmed at postmortem examination. Pituitary apoplexy is a clinical syndrome characterized by acute neurologic signs related to hemorrhagic infarction within a pituitary tumor. Pituitary apoplexy should be considered in patients with acute onset of blindness and altered mental status.