Detailed anatomic description of the lateral, transzygomatic approach to the middle fossa and rostral brainstem and its use in three dogs.

OBJECTIVE: To describe a craniectomy using a lateral, transzygomatic approach to the middle fossa and rostral brainstem, and to report clinical outcomes and complications in three dogs. ANIMALS: Two cadaver dogs and three client-owned dogs. Two of the client-owned dogs with middle fossa lesions, and one with a rostral brainstem lesion. METHODS: Two cadavers were used to describe the lateral, transzygomatic surgical approach to the middle fossa and rostral brainstem. The medical records of three dogs undergoing this surgical approach were reviewed for data on signalment, preoperative and postoperative neurological status, diagnostic imaging, surgical technique, complications, and outcome. RESULTS: Indications for this surgical approach included incisional biopsy (n = 1) and debulking surgery for brain lesions (n = 2). Definitive diagnoses were achieved in two cases, and tumor volume reduction in all cases. Two of the three dogs developed postoperative facial nerve paralysis ipsilateral to the surgical site, which resolved within 2 and 12 weeks after surgery. CONCLUSION: The lateral, transzygomatic approach provided useful access to ventrally located cerebral/skull base lesions in dogs without major complications.

Safety and interim survival data after intracranial administration of M032, a genetically engineered oncolytic HSV-1 expressing IL-12, in pet dogs with sporadic gliomas.

OBJECTIVE: The diagnosis of glioma remains disheartening in the clinical realm. While a multitude of studies and trials have shown promise, improvements in overall survival have been disappointing. Modeling these tumors in the laboratory setting has become increasingly challenging, given their complex in situ behavior and interactions for therapeutic evasion. Dogs, particularly brachycephalic breeds, are known to spontaneously develop gliomas that resemble human gliomas both clinically and pathophysiologically, making canines with sporadic tumors promising candidates for study. Typically, survival among these dogs is approximately 2 months with palliation alone. METHODS: The authors have completed the first stage of a unique phase I dose-escalating canine clinical trial in which the safety and tolerability of M032, a nonneurovirulent oncolytic herpes simplex virus-1 vector genetically engineered to express interleukin-12, are being studied in pet dogs with gliomas undergoing maximum safe tumor resection and inoculation of the cavity with the viral infusate. RESULTS: Twenty-five canine patients were enrolled between January 2018 and August 2020. One patient was electively withdrawn from the trial by its owner, and 3 did not receive the virus. For the 21 dogs that remained, 13 had high-grade gliomas, 5 had low-grade gliomas, and 3 were undetermined. According to histopathological analysis, 62% of the tumors were oligodendrogliomas. At the time of this report, the median overall survival from the date of treatment was 151 days (± 78 days). No significant adverse events attributable to M032 or dose-limiting toxicities have been observed to date. CONCLUSIONS: In this largest study of oncolytic viral therapy for canine brain tumors to date, treatment with M032 did not cause harm and the combination of surgery and oncolytic viral therapy may have contributed to prolonged survival in pet dogs with spontaneous gliomas. Forthcoming in-depth radiographic, immunohistochemical, and genetic analyses will afford a more advanced understanding of how this treatment impacts these tumors and the immune system. Our goal is to utilize these findings bitranslationally to inform human studies and refine therapies that will improve outcomes in both humans and pet dogs with gliomas.

Acute cerebrovascular event in a dog with polycythemia vera.

A 1-year-old neutered male Labrador retriever mixed breed dog was referred for peracute onset of ataxia and seizures. Hematocrit at presentation was 84%. Magnetic resonance imaging of the brain revealed a lesion in the right caudate nucleus consistent with infarction. Postmortem findings were consistent with polycythemia vera and presumed secondary cerebral infarction.

Événement cérébrovasculaire aigu chez un chien atteint de polycythémie vraie. Un Labrador retriever mâle âgé de 1 an a été référé pour l'apparition suraiguë d'ataxie et de crises d'épilepsie. L'hématocrite était de 84 % à la présentation. L'imagerie par résonance magnétique du cerveau a révélé une lésion dans le noyau caudé droit compatible avec à un infarcissement. Les résultats post mortem étaient conformes à une polycythémie vraie et à un infarcissement cérébral secondaire présumé.(Traduit par Isabelle Vallières).

Foramen magnum decompression surgery in 23 Chiari-like malformation patients 2007-2010: outcomes and owner survey results.

Chiari-like malformation (CLM) with syringomyelia (SM) in dogs is particularly prominent in the Cavalier King Charles spaniel breed, but has also been reported in several other small breed dogs. Over a period of 3 years, 23 canine patients were treated surgically for CLM-SM. Surgery consisted of foramen magnum decompression, durotomy, duraplasty, and free autogenous adipose tissue grafting (fat graft). All patients were re-evaluated clinically at least 1 month after surgery and some up to 3 years after surgery. Improvement was noted on all clinical evaluations. A questionnaire was mailed to all 23 owners after a period of at least 1 year after surgery. Seventeen surveys were returned. No patient has required additional surgery to date, 94% (16/17) had some improvement in quality of life after surgery, and none were judged to deteriorate to less than the pre-surgical status. The authors conclude that this surgical procedure, combined with medical therapy, resulted in favorable long-term outcomes.

Chirurgie de décompression du trou occipital chez 23 patients atteints de malformation semblable à celle du syndrome de Chiari 2007­2010 : résultats et données du sondage auprès des propriétaires. Une malformation semblable à celle du syndrome de Chiari (MSC) avec syringomyélie (SM) chez les chiens est particulièrement prépondérante chez la race d'épagneuls Cavalier King Charles, mais elle a aussi été signalée chez plusieurs autres races de petits chiens. Pendant une période de trois ans, 23 patients canins ont été traités par chirurgie pour le MSC-SM. La chirurgie consistait à faire une décompression du trou occipital, une durotomie, une duraplastie et une greffe de tissu adipeux autogène (greffe de graisse). Tous les patients ont été réévalués cliniquement au moins 1 mois après la chirurgie, puis environ 3 ans après la chirurgie. Une amélioration a été notée dans toutes les évaluations cliniques. Un questionnaire a été envoyé par la poste aux 23 propriétaires après une période d'au moins un an suite à la chirurgie. Dix-sept sondages ont été retournés. Aucun patient n'a eu besoin de chirurgie additionnelle jusqu'à maintenant, 94 % (16/17) ont eu une certaine amélioration de la qualité de vie après la chirurgie et aucun n'a été jugé comme ayant subi une détérioration de son état avant la chirurgie. Les auteurs concluent que cette intervention chirurgicale, combinée avec un traitement médical, a produit des résultats favorables à long terme.(Traduit par Isabelle Vallières).

Perspectives on pharmacologic strategies in the management of meningoencephalomyelitis of unknown origin in dogs.

There are many non-infectious inflammatory diseases, assumed to be immune-mediated in origin, recognized to affect the nervous system in canine patients. Concentrating on meningoencephalomyelitis of unknown origin, we will discuss the medications used to treat the underlying disease process, focusing on their adverse effects, therapeutic monitoring when necessary and effectiveness. The literature overwhelmingly supports the use of a steroid/ Cytosar® or steroid/ cyclosporine treatment protocol with the steroid tapered after the acute phase of the disease, leaving the secondary medication to control the disease long term. The decision on when and how quickly to taper the steroid is clinician dependent as a best practices has not been established in the literature. Also discussed will be the supportive care treatments often needed in the acute phase of these patients' diagnosis and treatment such as anti-edema and anti-epileptic agents.

Case report: Surgical removal of an intradural and intramedullary brainstem foreign body in a young German Shepherd.

A young, female German Shepherd was presented for evaluation of a progressive, mildly ambulatory tetraparesis with severe neck pain. All segmental reflexes were intact, and the paresis was more severe on the right thoracic and pelvic limbs. Diagnostic imaging (radiographs and computed tomography) revealed 2 metallic linear foreign bodies lodged at the right side of the cervicomedullary junction. A modification of the previously described ventral craniectomy approach was performed and after removal of a portion of the basioccipital bone using a nitrogen powered drill, the foreign bodies were removed. Over a period of 3 months, the patient made a full recovery.

CSF from a puppy with a cerebral vascular hamartoma.

A 9-week-old puppy with refractory seizures and a dome-shaped head presented to the Mississippi State College of Veterinary Medicine Specialty Center for suspected hydrocephalus. Computerized tomography (CT) findings included transtentorial herniation and an intra-axial mass with dystrophic mineralization. Cerebrospinal fluid analysis revealed an increased nucleated cell count of 1100/µl (RI < 5/µl), erythrocyte count of 2.2 × 106 /µl, and markedly increased microprotein of 1939 mg/dl (RI < 30 mg/dl). On cytologic examination of the CSF, numerous erythrophagocytic, and hemosiderin-laden macrophages were observed, which indicated chronic active hemorrhage. Many neutrophils, macrophages, and lymphocytes that contained numerous intracytoplasmic, pleomorphic, bright yellow crystals were observed. Considering the ongoing hemorrhage, the crystals were presumed to be hematoidin. A biopsy with histopathology was performed on the intra-axial mass, and the results were consistent with a vascular hamartoma. We speculate that the formation of these crystals was related to the ongoing hemorrhage associated with the vascular hamartoma. Identification of these crystals may be useful to aid in the identification of chronic hemorrhage associated with vascular malformations or lesions within the central nervous system.

Intraoperative Ultrasound Applications in Intracranial Surgery.

The methods and use of intraoperative ultrasound in 33 canine and five feline patients and its ability to localize and identify anatomical structures and pathological lesions in canines and felines undergoing intracranial surgery are described from a case series. All were client-owned referral patients admitted for neurologic evaluation, with an advanced imaging diagnosis of an intracranial lesion, and underwent surgical biopsy or surgical removal of the lesion. Medical records, retrieval and review of imaging reports, and characterization of findings for all canine and feline patients show that intraoperative ultrasound guidance was used in intracranial procedures during the period of 2012 and 2019. Twenty-nine of the canine patients had intracranial tumors. The remainder had various other conditions requiring intracranial intervention. Three of the feline patients had meningiomas, one had a depressed skull fracture, and one had an epidural hematoma. The tumors appeared hyperechoic on intraoperative ultrasound with the exception of cystic portions of the masses and correlated with the size and location seen on advanced imaging. Statistical comparison of the size of images seen on ultrasound and on MRI for 20 of the canine tumors revealed no statistical differences. Neuroanatomical structures, including vascular components, were easily identified, and tumor images correlated well with preoperative advanced imaging. The authors conclude that intraoperative ultrasound is a valuable asset in intracranial mass removals and can augment surgical guidance in a variety of intracranial disorders that require surgery. This is the first known publication in veterinary surgery of using intraoperative ultrasound as a tool in the operating theater to identify, localize, and monitor the removal/biopsy of intracranial lesions in small animals undergoing craniotomy/craniectomy.

The One Health Consortium: Design of a Phase I Clinical Trial to Evaluate M032, a Genetically Engineered HSV-1 Expressing IL-12, in Combination With a Checkpoint Inhibitor in Canine Patients With Sporadic High Grade Gliomas.

As the most common and deadly of primary brain tumors, malignant gliomas have earned their place within one of the most multifaceted and heavily-funded realms of medical research. Numerous avenues of pre-clinical investigation continue to provide valuable insight, but modeling the complex evolution and behavior of these tumors within a host under simulated circumstances may pose challenges to extrapolation of data. Remarkably, certain breeds of pet dogs spontaneously and sporadically develop high grade gliomas that follow similar incidence, treatment, and outcome patterns as their human glioma counterparts. The most malignant of these tumors have been refractory to limited treatment options despite aggressive treatment; outcomes are dismal with median survivals of just over 1 year in humans and 2 months in dogs. Novel treatments are greatly needed and combination therapies appear to hold promise. This clinical protocol, a dose-escalating phase I study in dogs with sporadic malignant glioma, represents a first in comparative oncology and combination immunotherapy. The trial will evaluate M032, an Interleukin-12 expressing Herpes Simplex virus, alone and combined with a checkpoint inhibitor, Indoximod. Extensive pre-clinical work has demonstrated safety of intracranial M032 administration in mice and non-human primates. M032 is currently being tested in humans with high-grade malignant gliomas. Thus, in a novel fashion, both canine and human trials will proceed concurrently allowing a direct "head-to-head" comparison of safety and efficacy. We expect this viral oncolytic therapy to be as safe as it is in human patients and M032 to (a) infect and kill glioma cells, producing a virus and tumor cell antigen-rich debris field; (b) provide an adjuvant effect due to liberation of viral DNA, which is rich in unmethylated CpG sequences that "toggle" TLR-9 receptors; and (c) express IL-12 locally, stimulating induction of TH1 lymphocytes. The resultant immune-mediated anti-viral responses should, through cross-epitope spreading, translate into a strong response to tumor antigens. The ability to compare human and dog responses in real time affords the most stringent test of suitability of the dog as an informative model of human brain tumors. Subsequent studies will allow canine trials to properly inform the design of human trials.

Compressive myelopathy of the cervical spine in Komodo dragons (Varanus komodoensis).

Cervical subluxation and compressive myelopathy appears to be a cause of morbidity and mortality in captive Komodo dragons (Varanus komodoensis). Four cases of cervical subluxation resulting in nerve root compression or spinal cord compression were identified. Three were presumptively induced by trauma, and one had an unknown inciting cause. Two dragons exhibited signs of chronic instability. Cervical vertebrae affected included C1-C4. Clinical signs on presentation included ataxia, ambulatory paraparesis or tetraparesis to tetraplegia, depression to stupor, cervical scoliosis, and anorexia. Antemortem diagnosis of compression was only confirmed with magnetic resonance imaging or computed tomography. Treatment ranged from supportive care to attempted surgical decompression. All dragons died or were euthanatized, at 4 days to 12 mo postpresentation. Studies to define normal vertebral anatomy in the species are necessary to determine whether the pathology is linked to cervical malformation, resulting in ligament laxity, subsequent instability, and subluxation.

Suprascapular nerve decompression for treatment of neuropathy in a bucking bull.

CASE DESCRIPTION: A 3-year-old 639-kg (1,406-lb) American bucking bull was examined because of a 4-day history of right forelimb lameness that began after the bull sustained an injury to the right shoulder region while exiting the chute during a rodeo. CLINICAL FINDINGS: A 10 × 10-cm soft tissue swelling was present over the right shoulder region. Ultrasonographically, the contour of the scapular spine, bicipital bursa, bicipital tendon, and greater tubercle of the humerus appeared unremarkable; the swelling appeared to be a hematoma overlying the distal aspect of the scapula. No external wounds, palpable joint effusion, or swellings were noted on examination of the distal portions of the limbs. The bull developed atrophy of the supraspinatus and infraspinatus muscles with lateral abduction of the shoulder joint when walking. Electromyography revealed decreased innervation to the supraspinatus and infraspinatus muscles consistent with suprascapular neuropathy. TREATMENT AND OUTCOME: The suprascapular nerve was surgically decompressed by removing the entrapping hematoma and periosteum and performing a notch resection of the scapula; dexamethasone (40 mg) was administered prior to closure. The bull was discharged 5 days after surgery; no lameness was evident at the time of discharge. The owner was instructed to restrict the bull to a stall or small pen for 6 weeks. Four months after surgery, the muscle atrophy had substantially improved, and the bull returned to bucking. CLINICAL RELEVANCE: Findings suggested that suprascapular neuropathy can develop in bulls secondary to injury and that suprascapular nerve decompression may improve nerve function, muscle atrophy, and gait.

A modified ventral approach to the atlantoaxial junction in the dog.

OBJECTIVE: To describe and evaluate a surgical technique using a modified ventral approach for stabilization of the atlantoaxial (AA) junction in dogs with AA subluxation. STUDY DESIGN: Retrospective study. ANIMALS: Dogs (n=5) with AA subluxation. METHODS: Medical records (2000-2006) of 5 dogs with AA treated by stabilization via a right parasagittal approach were reviewed and outcome assessed by clinical examination and phone interviews with owners. RESULTS: The AA joint was clearly visualized and fixation devices were placed in all dogs. A right parasagittal approach provided excellent access to the AA junction and avoided dissection around the thyroid gland, trachea, and recurrent laryngeal nerve. Recovery was considered good to excellent by owners, and dogs returned to good function. CONCLUSIONS: A right parasagittal approach to the AA junction provides improved exposure and allows for surgical stabilization with minimal complications. CLINICAL RELEVANCE: In dogs that require surgical stabilization of the AA joint, a right parasagittal approach should be considered. This approach offers advantages over the standard ventral median approach by improved surgical exposure, less dissection, and provides protection of vital structures during insertion of fixation devices used for ventral AA stabilization.

Constrictive myelopathy secondary to hypoplasia or aplasia of the thoracolumbar caudal articular processes in Pugs: 11 cases (1993-2009).

OBJECTIVE: To report thoracolumbar caudal articular process malformations with secondary constrictive fibrosis of the spinal cord in Pugs. DESIGN: Retrospective case series. ANIMALS: 11 Pugs with neurologic dysfunction resulting from constriction of fibrous tissue secondary to thoracolumbar caudal articular process malformation and 5 Pugs with no neurologic dysfunction. PROCEDURES: Medical records of dogs with myelopathy presumably caused by constriction of fibrous tissue secondary to thoracolumbar caudal articular process malformation at 2 referral institutions between 1993 and 2009 were reviewed. Dogs were included in the study if hypoplastic or aplastic thoracolumbar caudal articular processes were present on radiographs, CT images, or MRI images. RESULTS: The most common neurologic examination findings were paraparesis with ataxia or paraplegia but no evidence of hyperpathia along the vertebral column. All dogs' neurologic lesion localization was to the T3-L3 spinal cord segments. Median age at examination was 7. 7 years (range, 2 to 11 years). Five of 11 dogs had a history of unrelated trauma. Four of 11 dogs had urinary or fecal incontinence. Eight of 11 dogs underwent surgical exploration. Despite surgical intervention, all dogs that survived surgery continued to have neurologic deficits. CONCLUSIONS AND CLINICAL RELEVANCE: In the present study, presence of aplastic or hypoplastic articular processes in the thoracolumbar region did not always produce neurologic signs. However, fibrous constrictive myelopathy should be considered in Pugs with pelvic limb gait and postural reaction deficits and lack of hyperpathia upon palpation of the vertebral column. Additional studies are warranted to further characterize the disease process and determine the most effective means of treatment.