Jennifer Stewart

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.

Canine dacryolithiasis: a case description and mineral analysis.

A 4-year-old, female, spayed, Labrador retriever was presented with a painless swelling of the left ventromedial eyelid and epiphora of 3 months duration. Bilateral patency of the nasolacrimal system was confirmed by the appearance of fluorescein dye at both nares. Ultrasonography revealed a well-demarcated fluid-filled structure containing echogenic ill-defined material in close proximity to the nasolacrimal system. A transconjunctival surgical approach confirmed the close anatomical proximity of the cyst and the absence of a communication with the inferior canaliculus. The cyst contained multiple intraluminal calculi (dacryoliths). Following surgical excision of the cyst, the epiphora resolved and no recurrence was noted over a 12-month follow-up period. On histopathology, the cystic structure was lined by stratified squamous epithelium, consistent with lacrimal canaliculus epithelium. Presumed progression of a canalicular diverticulum to a cyst with the formation of intraluminal dacryoliths was suspected. Mineral analysis of the dacryoliths revealed a calcium carbonate composition.

Disseminated mast cell tumor infiltrating the sphenoid bone and causing blindness in a dog

Mast cell tumors are found in most organs and tissues with variable biologic behavior in dogs. This case illustrates the clinical and magnetic resonance imaging (MRI) findings in a dog with disseminated mast cell tumor infiltrating the sphenoid bones. A 6-year-old male neutered Greyhound presented with a 3-day history of acute onset of blindness. General physical examination was normal. Neurological examination revealed mildly disorientated mental status, absent menace response in both eyes, bilaterally decreased vestibulo-oculocephalic reflexes and absent direct and consensual pupillary light reflex in both eyes. An electroretinogram indicated normal retinal function in both eyes. A lesion involving the middle and rostral cranial fossa was suspected. Hematology and serum biochemistry were normal except decreased urea (1.2 mmol/L). MRI of the head revealed heterogeneous signal intensity of the sphenoid bones on T2-weighted images and loss of their normal internal architecture. Cerebrospinal fluid analysis was normal. Abdominal ultrasound revealed hepatosplenomegaly and mesenteric lymphadenopathy. Fine needle aspirates were taken from the jejunal lymph nodes and the spleen. Results were consistent with disseminated mast cell tumor. The owner declined any treatment and the dog was euthanatized. Postmortem examination confirmed disseminated mast cell tumor affecting multiple organs, including the sphenoid bones. To our knowledge, this is the first case describing MRI features of disseminated mast cell tumor affecting the sphenoid bones and causing acute onset of blindness in a dog.

IMAGING DIAGNOSIS–UNILATERAL TRIGEMINAL NEURITIS MIMICKING PERIPHERAL NERVE SHEATH TUMOR IN A HORSE

A 16-year old Warmblood gelding presented with a nonhealing corneal ulcer and absent corneal sensation in the left eye. A lesion affecting the maxillary and ophthalmic branches of the left trigeminal nerve was suspected. Magnetic resonance (MR) imaging identified marked thickening of the ophthalmic and maxillary branches of the left trigeminal nerve. The nerve was iso- to hypointense on T1-weighted and T2-weighted images with heterogeneous enhancement. A peripheral nerve sheath tumor was suspected, however granulomatous neuritis was histopathologically confirmed. These inflammatory changes can result in severe nerve enlargement and should be considered with MR findings suggestive of peripheral nerve sheath tumor.

A case of giant cell tumor of soft parts in a horse

A 12-year-old British Warmblood mare was examined by the referring veterinarian for evaluation of a cutaneous lesion on the dorsal thorax to the right of the midline. Cytologic examination of fine-needle aspirates from the mass was supportive of a giant cell tumor of soft parts (GCTSP). Laser surgical excision and postoperative methyl aminolevulinate (MAL) photodynamic therapy (PDT) were performed. Histologic examination of the mass confirmed the cytologic diagnosis. At 8 months from surgery, no evidence of recurrence has been observed. Giant cell tumors of soft parts are rare cutaneous neoplasms, observed in several domestic species, including the horse where they commonly appear as superficial cutaneous lesions without aggressive biologic behavior. Previously classified as giant cell variant of malignant fibrous histiocytoma, these superficial tumors have now been designated as giant cell tumors of soft tissue or giant cell tumors of low malignant potential within the category of fibrohistiocytic neoplasms.

What is your diagnosis? Swelling of the left antebrachium and carpus in a horse

An 8-month-old Thoroughbred colt was presented to Newmarket Equine Hospital with a 6-week history of swelling of the left antebrachium and carpus. On admission, the horse was bright and alert. Temperature, pulse, and respiration rate were normal. The animal exhibited marked left forelimb lameness. There was marked tense distension of the carpal sheath of the extensor carpi radialis with swelling extending proximally beyond the musculotendinous junction. Carpal flexion was reduced to approximately 10° only. Radiographic examination demonstrated periosteal new bone on the dorsodistal radius, bordering the extensor carpi radialis grooves. Ultrasonography revealed extensive disruption of the extensor carpi radialis muscle and displacement of its tendon of insertion. CBC and serum biochemical profile were unremarkable. At tenoscopy under general anesthesia, the extensor carpal radialis tendon sheath was filled with organized hemorrhagic tissue which extended also proximally, infiltrating themuscle.Multiple small incisional biopsies and impression smears were taken from the lesion. The impression smears were stained with Wright–Giemsa (Figure 1A and B). A

Cerebral coenurosis in a cat

A two-year-old female Birman cat presented with progressive abnormal behaviour, lethargy and circling towards the left. MRI demonstrated a large, solitary, intraxial expansile thin-walled cyst, without surrounding oedema or enhancement, in the left frontoparietal region. Severe subfalcian, caudal transtentorial and foramen magnum herniation were present. The owners declined treatment and the cat was euthanased. Postmortem examination demonstrated a coenural cyst with multiple larval protoscolices molecularly confirmed as Taenia serialis. Recognition of characteristic MRI findings of feline cerebral coenurosis is necessary if antemortal diagnosis and management of this, to date, invariably fatal neurological condition is possible.

MRI findings of diffuse polioencephalopathy secondary to ethylene glycol intoxication in a dog

A six-year-old, female spayed German shepherd dog presented with an acute onset of disorientation, lethargy, polydipsia, vomiting and one episode of seizure activity. MRI of the brain revealed diffuse contrast enhancement of meninges and the grey matter in the cerebral hemispheres and cerebellum on T1-weighted images. Abdominal ultrasonography showed bilateral renal changes. The dog deteriorated and was euthanised. On postmortem examination small oxalate crystals were identified in the kidneys, meningeal vessels and capillaries of the grey matter confirming ethylene glycol intoxication.

Unilateral eyelid lesion and ophthalmologic findings in an aardvark (Orycteropus afer): case report and literature review.

OBJECTIVE To summarize the medical knowledge surrounding aardvarks to date, to describe the ophthalmic examination of a specimen with a chronic history of an upper eyelid lesion, of an assumed blind left eye, and to detail the anesthesia procedure performed. PROCEDURE A 23-year-old aardvark was examined under general anesthesia and multiple ocular abnormalities were detected in the left eye (globe deviation, corneal opacities, iridodonesis, and aphakia). A thickening of the palpebral conjunctiva affecting the medial upper eyelid with erosion of the normal eyelid margin anatomy was identified. The adnexal lesion was resected by a wedge resection and histopathology was performed. Suture breakdown 3 days postoperatively required a second surgery, where buried sutures were used. The surgical techniques and postoperative care are discussed. RESULTS The histopathology revealed mucosal hyperplasia and moderate neutrophilic and lymphoplasmacytic blepharitis. No causal organisms were identified. Following initial wound dehiscence and a modified surgical technique, the upper eyelid healed without complication and retained complete function. CONCLUSIONS The eyelid lesion involved a benign inflammatory and hyperplastic pathology of unknown etiology. Adjusting routine ophthalmic surgical techniques to wildlife and zoo animals can be challenging and complicated. It is important to understand the nature of the animals being managed, their circadian cycle, and habitat, to adjust and individualize the surgical approach, instrumentation, suture material, and perioperative treatment.

Spontaneous non-traumatic tension pneumocephalus in a dog with a nasal meningoencephalocele

A 1.5-year-old neutered male Border collie was presented with acute onset left forebrain signs and unilateral nasal discharge 14 months after MRI diagnosis of nasal meningoencephalocele. Subsequent MRI revealed intraventricular pneumocephalus with a gas-filled tract extending to the rostral aspect of the intranasal brain parenchyma. Transient clinical improvement was noted with medical management, with euthanasia eight months post diagnosis due to deteriorating neurological status. The diagnoses of intraventricular pneumocephalus and frontoethmoidal meningoencephalocele were confirmed post mortem. This is the first reported case of non-traumatic tension pneumocephalus in a dog and the first report of pneumocephalus associated with a nasal meningoencephalocele in a dog.