Intracranial Virotherapy for a Canine Hemangioma.

Intracranial hemangiomas are rare neoplastic lesions in dogs that usually appear with life-threatening symptoms. The treatment of choice is tumor resection; however, complete resection is rarely achieved. The patient's prognosis therefore usually worsens due to tumor progression, and adjuvant treatments are required to control the disease. Oncolytic viruses are an innovative approach that lyses the tumor cells and induces immune responses. Here, we report the intratumoral inoculation of ICOCAV15 (an oncolytic adenovirus) in a canine intracranial hemangioma, as adjuvant treatment for incomplete tumor resection. The canine patient showed no side effects, and the tumor volume decreased over the 12 months after the treatment, as measured by magnetic resonance imaging using volumetric criteria. When progressive disease was detected at month 18, a new dose of ICOCAV15 was administered. The patient died 31.9 months after the first inoculation of the oncolytic adenovirus. Furthermore, tumor-infiltrated immune cells increased in number after the viral administrations, suggesting tumor microenvironment activation. The increased number of infiltrated immune cells, the long survival time and the absence of side effects suggest that ICOCAV15 could be a safe and effective treatment and should be further explored as a novel therapy for canine hemangiomas.

Systemic cellular viroimmunotherapy for canine high-grade gliomas.

BACKGROUND: Oncolytic viruses constitute a growing field of interest, both in human and veterinary oncology, given that they are particularly helpful for treating non-surgical tumors and disseminated cancer, such as high-grade gliomas. Companion dogs present malignant gliomas with biological, genetic, phenotypic, immunological, and clinical similarities to human gliomas. These features favor comparative approaches, leading to the treatment of canine oncological patients to achieve translational applications to the human clinic. The systemic administration of oncolytic viruses presents a challenge due to their limitations in effectively targeting tumors and metastases. Therefore, the aim of this study is to evaluate the safety and antitumor activity of a virotherapy used in spontaneous canine tumors. METHODS: Ten dogs with high-grade rostrotentorial gliomas underwent weekly systemic endovenous cellular virotherapy with dCelyvir (canine mesenchymal stem cells infected with the canine oncolytic adenovirus ICOCAV17) for 8 weeks. Efficacy was determined in seven dogs according to the Response Assessment in Veterinary Neuro-Oncology criteria considering clinical status and MRI measurements. Medical history, physical and neurological examinations, and vaccination status were evaluated prior to and during follow-up. Safety was evaluated by physical examinations and hematological and biochemical changes in peripheral blood. Immune populations were analyzed by flow cytometry in peripheral blood and by gene expression and immunohistochemistry in the tumor microenvironment. RESULTS: The treatment was well tolerated and major adverse effects were not observed. Two dogs had partial responses (76% and 86% reduction in tumor size), and 3/7 showed stable disease. ICOCAV17 was detected in peripheral blood in nine dogs, and a correlation between the ICOCAV17 particles and anti-canine adenovirus (CAV) antibodies was observed. ICOCAV17 was detected in 3/9 tumor tissues after necropsies. Regarding tumor-infiltrating lymphocytes, the dogs with disease stabilization and partial response tended to have reduced memory B-cell infiltration and increased monocyte/macrophage lineage cells. CONCLUSIONS: These findings indicate that dCelyvir is safe and presents efficacy in canine rostrotentorial high-grade gliomas. These data are relevant to the ongoing phase Ib regulated human clinical trial that is administering this virotherapy to children, adolescents, and young adults with diffuse pontine glioma. Celyvir should be further explored as a treatment in veterinary and human neuro-oncology.

Dorsal Atlantoaxial Ligament Hypertrophy as a Cause for Clinical Signs in Dogs with Dens Abnormalities.

The objective of this study is to suggest clinical and subclinical atlantoaxial (AA) instability as a cause for dorsal AA ligament hypertrophy responsible for clinical signs in dogs with dens abnormalities. Clinical information from five dogs with malformed dens and dorsal spinal cord compression at the AA junction was collected. All dogs had neck pain, associated with tetraparesis in three cases. Radiological examination revealed hypoplastic dens in two dogs and a defect in its ossification in the other three. Stress views were able to demonstrate obvious AA instability only in two cases, but it was suspected in the other owing to response to surgical fixation of the joint and the presence of a dorsal compressive band, which was considered an enlarged dorsal AA ligament. Surgical and histopathological examination of compressive tissue confirmed hypertrophy of the ligament. Long-term prognosis in the four operated cases, either by dorsal decompression and ventral fixation or by ventral fixation alone, was excellent. A malformed dens can cause subclinical instability, unnoted in dynamic studies. As instability may lead to hypertrophy of joint ligaments, soft tissue changes (specifically dorsal AA ligament hypertrophy) points out this instability and the need for joint fixation if surgical management is required.

Palliative ventriculoperitoneal shunting in dogs with obstructive hydrocephalus caused by tumors affecting the third ventricle.

BACKGROUND: Hypertensive or obstructive hydrocephalus is a common complication in dogs with tumors affecting the third ventricle for which few therapeutic options are available. OBJECTIVES: To describe signalment, neurological status, and pre- and postsurgical findings, complications and survival time in 4 dogs with obstructive hydrocephalus caused by third ventricle tumors that were palliatively treated using ventriculoperitoneal shunting (VPS). ANIMALS: Four client-owned dogs with obstructive hydrocephalus caused by tumors affecting the third ventricle. METHODS: Medical records were reviewed for dogs diagnosed with third ventricular tumors. Inclusion criteria were complete medical record, advanced diagnostic imaging for review, and VPS as sole surgical treatment. RESULTS: At the time of diagnosis, all patients displayed acute onset and rapidly progressive diffuse intracranial clinical signs. On advanced imaging, all dogs had a homogeneously enhancing mass occupying or collapsing the third ventricle as well as obstructive hydrocephalus. All of the dogs underwent VPS of the most dilated lateral ventricle. In 2 of the patients, intracranial hypertension followed by normotension after VPS placement was confirmed intraoperatively by means of direct intracranial pressure monitoring. Excellent clinical improvement was observed in all dogs immediately after surgery. Three patients required a second VPS in the contralateral lateral ventricle 3, 7 and 11 months after the first surgery, all of them with renewed improvement in clinical signs. CONCLUSION AND CLINICAL IMPORTANCE: Ventriculoperitoneal shunting is a rapid and effective treatment for patients with obstructive (hypertensive) hydrocephalus caused by tumors located within the third ventricle.

Median manubriotomy for ventral access to the caudal cervical and cranial thoracic spine.

OBJECTIVE: To describe median manubriotomy to access the ventral aspect of the caudal cervical and cranial thoracic spine and report the outcomes in dogs with lesions affecting the spinal cord at C6-T2 vertebral bodies. To evaluate possible complications of this technique and clinical outcomes. STUDY DESIGN: Cadaveric study and short case series. STUDY POPULATION: Two cadavers and nine dogs with lesions affecting the spinal cord at C6, C7, T1 or T2 vertebral bodies or corresponding intervertebral spaces. METHODS: Two cadavers were used for demonstration purposes. Medical records (2013-2019) were reviewed for dogs undergoing median manubriotomy to facilitate access to the ventral aspect of C6-T2 vertebral bodies and/or corresponding intervertebral disc spaces. Data on preoperative and postoperative neurological status and diagnostic imaging, surgical technique, and complications were retrieved. RESULTS: Indications for surgery included C7-T1 disc extrusions in five dogs, caudal cervical misalignment in three dogs, and C7-T1 and T1-T2 disc protrusions in one dog. The vertebral bodies of C6 to T2 were consistently visualized after median manubriotomy. Preoperative clinical signs resolved in five dogs and improved in two dogs. One dog was euthanized for lack of improvement, and one dog died of pulmonary thromboembolism. CONCLUSION: Median manubriotomy improved the surgical access to the ventral aspect of caudal cervical and cranial thoracic spine without related complications. CLINICAL SIGNIFICANCE: Median manubriotomy can be considered in dogs undergoing ventral decompression and/or stabilization of C7-T1 and T1-T2 intervertebral disc spaces.

Intervertebral T3-T4 Disc Extrusions in Two German Shepherd Dogs.

Although intervertebral disc extrusions are extremely frequent in dogs, those affecting the cranial thoracic spine in large-breed dogs have not been reported. In this case report, the clinical, radiological, surgical, and histopathological findings in two German shepherd dogs with T3-T4 disc extrusions are reported. Clinical and imaging findings (acute onset and radiological evidence of lateralized disc material dispersed beyond the margins of the intervertebral disc space) allowed proper diagnosis of disc extrusion. Decompressive surgery via hemilaminectomy was performed in both patients with favorable outcomes. Intervertebral disc extrusions should be considered as a differential diagnosis of large-breed dogs with acute onset, upper-thoracic spinal cord disease. Imaging findings can aid in differentiating thoracic intervertebral disc extrusions from protrusions, thus leading to appropriate treatment.

Surgical management of a brain abscess due to plant foreign body in a dog.

Background: Intracranial abscesses as a result of grass awn migration have been rarely described in the veterinary literature. The identification of their radiological features is mandatory for proper diagnosis. As occurs with abscesses in other organs, surgical drainage and directed antibiotic therapy should be considered the treatment of choice. Case Description: A clinical case of a Great Dane dog with forebrain signs and magnetic resonance imaging and computed tomography findings compatible with intracranial abscess associated with inflammatory changes in orbital musculature is described. An exploratory rostro-tentorial craniotomy with durotomy was performed, allowing the drainage of purulent content and the extraction of a plant foreign body from the cerebral parenchyma. Antibiotic treatment was instituted and the patient was discharged without recurrence of neurological deficits other than quarterly seizures. Six months later, revision magnetic resonance was performed, revealing the resolution of the intracranial lesion and the normalization of the extracranial tissues. Conclusion: This is the first case in veterinary literature in which a grass awn has been surgically extracted from the brain of a dog with long-term outcome described. Observed changes in the extracranial musculature were fundamental to establish the pre-surgical diagnosis of a migratory foreign body.

Brainstem oligodendroglioma in a puppy.

A 5 mo old male golden retriever presented for evaluation of an acute onset, progressive neurologic disease. Although computed tomography (CT) was unremarkable, MRI identified an ill-defined mass located in the medulla, which was considered likely responsible for the clinical signs. The imaging features closely resembled the classic features of human brainstem gliomas in the pediatric population. Histopathologic examination confirmed the lesion to be an anaplastic oligodendroglioma.

MR cisternography/myelography of post-traumatic spinal CSF fistulae and meningeal lesions in small animals.

BACKGROUND: The diagnosis of post-traumatic spinal cerebrospinal fluid (CSF) fistulae due to dural tears or lesions remains a challenge. Thus far, CT myelography is the standard test used to diagnose these complications. PURPOSE: To evaluate the diagnostic ability of gadolinium-enhanced MR cisternography/myelography (intrathecal gadopentate dimeglumine or Gd-DTPA) in small animals that had experienced accidental spinal trauma. MATERIAL AND METHODS: Four dogs and one cat suffered traumatic accidents resulting in neurological deficits underwent spinal MRI with intrathecal Gd-DTPA after routine plain films and MR images. RESULTS: T2-weighted SE images showed high water content in the epidural space or in the surroundings of the vertebrae in four animals. MR myelography revealed CSF leakage in all of them. In two animals CSF leaks were observed exuding from the spinal canal and tracking towards adjacent loose fat and interfascial planes. In two other animals Gd-DTPA extravasation was diffusely collected in paraspinal tissues around the vertebral arch. In the fifth animal a focal pseudomeningocele was observed adjacent to the traumatized region. CONCLUSION: Intrathecal administration of Gd-DTPA is an effective method to reveal and confirm post-traumatic spinal CSF fistulae or other dural lesions in animals with potential application in humans.

Diverticulum of the third ventricle and absence of the interthalamic adhesion in a dog.

A 10-month-old male Pomeranian dog was examined for neurological abnormalities consistent with diffuse forebrain and cerebellar disease. Based on ultrasound and magnetic resonance imaging (MRI) a diagnosis of diverticulum of the third ventricle, partial agenesis of the corpus callosum, and absence of the interthalamic adhesion was made. As conservative treatment was unsuccessful, a ventriculoperitoneal shunt was placed.

Clinical, pathologic, and magnetic resonance imaging characteristics of canine disc extrusion accompanied by epidural hemorrhage or inflammation.

Our aim was to characterize the magnetic resonance (MR) imaging features of canine disc extrusion accompanied by epidural hemorrhage or inflammation. We correlated the imaging characteristics of this type of disc extrusion in 46 dogs and compared these features with clinical signs and pathologic findings. Data from 50 control dogs with MR imaging features of a disc extrusion with no associated hemorrhage or inflammation, characterized by a T2-hypointense extradural mass, were used for comparison of the relative location of the two types of lesions and prognosis. Disc extrusion causing epidural hemorrhage or inflammation is more common in the caudal aspect of the lumbar spine than disc extrusions that do not cause signs of hemorrhage or inflammation (P < 0.05) in MR images. In dogs with disc extrusion and associated epidural hemorrhage or inflammation, there was no association between MR imaging features and signalment, the presence or absence of hemorrhage, or pathologic findings. The appearance of the lesion created by disc extrusion with epidural hemorrhage and inflammation encompasses a wide variety of imaging features, likely related to the duration of the hemorrhage and associated inflammatory changes. In 10 of 46 dogs these secondary changes masked identification of the disc extrusion itself in the MR images. An awareness of the variety of MR imaging features of disc extrusion accompanied by extradural hemorrhage or inflammation is important to avoid making an incorrect diagnosis and to facilitate a proper surgical approach. The prognosis of dogs with disc extrusion accompanied by hemorrhage or inflammation does not appear to be different than for dogs with disc extrusion and without imaging signs of epidural hemorrhage or inflammation.

Imaging diagnosis: traumatic dural tear diagnosed using intrathecal gadopentate dimeglumine.

A dog with traumatic monoplegia had a spinal cord lesion, identified using conventional magnetic resonance imaging. In addition, the intrathecal use of gadopentate dimeglumine allowed identification of two sites of cerebrospinal fluid leakage from the vertebral canal, supporting a diagnosis of brachial plexus avulsion. Veterinary

Schistosoma reflexum in a cat: insights into aetiopathogenesis.

A foetal cat exhibiting multiple congenital malformations and meeting the criteria for being considered as a case of true schistosoma reflexum (SR) is described. SR in animals is briefly compared with relatively similar malformation entities in humans. Murine gene mutations producing severe ventral body wall defects associated with anomalies of internal organs and other structures are briefly reviewed. New insights into aetiopathogenic mechanisms possibly implicated in the development of SR are suggested. This is probably the first case of true SR reported in the cat.