The effects of neurectomy and hibernation on bone properties and the endocannabinoid system in marmots (Marmota flaviventris).

Hibernators have adapted a physiological mechanism allowing them to undergo long periods of inactivity without experiencing bone loss. However, the biological mechanisms that prevent bone loss are unknown. Previous studies found meaningful changes, between active and hibernating marmots, in the endocannabinoid system of many tissues, including bone. Cannabinoid receptors (CB1 and CB2) have divergent localization in bone. CB1 is predominately found on sympathetic nerve terminals, while CB2 is more abundant on bone cells and their progenitors. This study aimed to determine the contribution of innervation on endocannabinoid regulation of bone properties in hibernating (during torpor) and non-hibernating yellow-bellied marmots. Neurectomy, a model for disuse osteoporosis, was performed unilaterally in both hibernating and active marmots. Endocannabinoid concentrations were measured in bone marrow, cortical, and trabecular regions from fourth metatarsals of both hindlimbs using microflow chromatography-tandem quadrupole mass spectrometry. Trabecular bone architectural properties of fifth metatarsals were evaluated using micro-computed tomography. There were ligand-specific increases with neurectomy in active, but not hibernating, marmots. Trabecular bone architectural properties were not affected by neurectomy during hibernation, but did show some minor negative changes in active marmots. These findings suggest protection from bone loss in hibernating rodents is peripherally rather than centrally regulated. Furthermore, findings suggest even active marmots with normal metabolism are partially protected from disuse induced bone loss compared to laboratory rodents. Understanding the mechanism hibernators use to maintain bone density may guide development for novel bone loss prevention therapies.

Onscreen-guided resection of extra-axial and intra-axial forebrain masses through registration of a variable-suction tissue resection device with a neuronavigation system.

OBJECTIVES: To describe a novel surgical technique in which neuronavigation is used to guide a tissue resection device during excision of forebrain masses in locations difficult to visualize optically. STUDY DESIGN: Short case series. ANIMALS: Six dogs and one cat with forebrain masses (five neoplastic, two nonneoplastic) undergoing excision with a novel tissue resection device and veterinary neuronavigation system. METHODS: The animals and resection instrument were coregistered to the neuronavigation system. Surgery was guided by real-time onscreen visualization of the resection instrument position relative to the preoperative MR images. Surgical outcome was evaluated by calculating residual tumor volume according to postoperative MRI. RESULTS: The technique was technically simple and led to the collection of diagnostic tissue samples in all cases. Postoperative MRI was available in six cases, two with gross-total resection, three with near-total resection, and one with subtotal resection. CONCLUSION: Neuronavigation-guided resection of intra-axial and extra-axial brain masses with the resection device resulted in gross-total or near-total resection in five of six animals with tumors otherwise difficult to visualize. Risk of brain shift limited absolute reliance on navigation images. CLINICAL SIGNIFICANCE: Real-time neuronavigation assistance is a feasible method for guidance and successful resection of brain masses that are poorly visualized because of intra-axial or deep location, tumor appearance, or hemorrhage.

Determination of surgical exposure obtained with integrated endoscopic thoracolumbar hemilaminectomy in large-breed cadaveric dogs.

OBJECTIVE: To define boundaries of minimally invasive integrated endoscopic hemilaminectomy at 4 sites in the canine thoracolumbar spine. STUDY DESIGN: Experimental, randomized cadaveric study. ANIMALS: Six cadaver dogs that had been humanely euthanized for reasons unrelated to this study. METHODS: Hemilaminectomy was performed with an integrated endoscopic system at T11-12, T12-13, L1-2, and L2-3, 1 at each site, on the left or right side of each dog. Each site was randomly assigned either a 19-mm or a 23-mm cannula. The entire procedure, including soft tissue dissection, was performed through the cannula. Afterward, spines were imaged by computed tomography (CT) to measure the cranial and caudal extent of the hemilaminectomy from the center of the disc space. RESULTS: The mean ± SD cranial extent of the hemilaminectomy was 4.5 ± 1.4 mm for the 19-mm cannula and 5.6 ± 1.4 mm for the 23-mm cannulas (P = .0757). The caudal extent of the hemilaminectomy was 9.5 ± 2.2 mm for the 19-mm cannula and 10.3 ± 1.6 mm for the 23-mm cannula (P = .206). The mean length of the hemilaminectomy was 13.0 ± 1.5 mm for the 19-mm cannula and 15.0 ± 2.1 mm for the 23-mm cannula (P = .022). CONCLUSION: Integrated endoscopic systems were reliably used to access the spinal canal within the range of the above measurements relative to the disc space as identified by CT or magnetic resonance imaging. CLINICAL SIGNIFICANCE: Integrated endoscopy can be considered as an option in dogs with thoracolumbar disc extrusions or other pathology measuring within the parameters defined by this study. Access may be possible beyond the dimensions defined in this study with probing and repositioning.

Consensus recommendations on standardized magnetic resonance imaging protocols for multicenter canine brain tumor clinical trials.

The National Cancer Institute Comparative Brain Tumor Consortium, Patient Outcomes Working Group, propose a consensus document in support of standardized magnetic resonance imaging protocols for canine brain tumor clinical trials. The intent of this manuscript is to address the widely acknowledged need to ensure canine brain tumor imaging protocols are relevant and have sufficient equivalency to translate to human studies such that: (1) multi-institutional studies can be performed with minimal inter-institutional variation, and (2) imaging protocols are consistent with human consensus recommendations to permit reliable translation of imaging data to human clinical trials. Consensus recommendations include pre- and postcontrast three-dimensional T1-weighted images, T2-weighted turbo spin echo in all three planes, T2*-weighted gradient recalled echo, T2-weighted fluid attenuated inversion recovery, and diffusion weighted imaging/diffusion tensor imaging in transverse plane; field of view of ≤150 mm; slice thickness of ≤2 mm, matrix ≥ 256 for two-dimensional images, and 150 or 256 for three-dimensional images.

Magnetic Resonance Imaging Appearance and Mechanism of Action of Five Hemostatic Agents Used in Neurosurgery.

OBJECTIVE: To describe the magnetic resonance (MR) image appearance of 5 hemostatic agents placed in the brain, and to review their clinical application. STUDY DESIGN: Descriptive ex vivo and in vivo study. ANIMALS: Canine cadavers (n=4), client-owned dogs (n=4). METHODS: Heads from 4 canine cadavers were used, each with 5 hemostatic agents placed in specific locations in the brain. Hemostatic agents were used in their native form in 2 cadaveric brains, and in 2 others the materials were saturated with fresh whole blood prior to placement to mimic application in a field of active hemorrhage. The heads underwent MR imaging and the images were reviewed. Postoperative MRI images from 4 dogs undergoing brain tumor resection were retrospectively reviewed and compared to the images from the cadavers. All clinical cases and cadaveric specimens underwent surgical closure prior to MR imaging including placement of titanium mesh over the craniotomy defect with a dural graft of porcine small intestinal submucosa (SIS) sealed with Tisseel (fibrin sealant). RESULTS: The SIS and Tisseel used in the dural graft were consistently indistinguishable from the surrounding tissues on MR images. The MR imaging appearance of the remaining 4 hemostatic agents (Gelfoam, Avitene, Surgicel, and Floseal) placed on the surface or in the parenchyma of canine brain, varied with MR sequence weighting and blood saturation. CONCLUSION: Accurate evaluation of the degree of brain tumor resection on postoperative MR images requires careful differentiation between hemorrhage, residual tumor, and hemostatic agents implanted.

Canine intervertebral disc fenestration using a vacuum-assisted tissue resection device.

OBJECTIVE: Describe the use and feasibility of a novel vacuum-assisted tissue resection device (VRD) for canine intervertebral disc fenestration, and compare the effectiveness of manual fenestration to the VRD. STUDY DESIGN: Randomized prospective study. ANIMALS: Canine cadavers (n = 15). METHODS: A cadaveric lumbar spine study was performed to compare the use of manual fenestration to a novel VRD for intervertebral disc fenestration. Both fenestration groups were compared to a control group. Effectiveness of fenestration was assessed by calculating a ratio of remaining nuclear weight postfenestration to total nuclear volume. Fenestrated discs with lower ratios were indicative of greater removal of nucleus pulposus. RESULTS: There was a statistically significant reduction in mean ratio (±SD) of remaining nuclear weight to volume with both fenestration groups compared to controls (0.39 ± 0.07; P < .001). There was an improved ratio using the VRD (0.23 ± 0.09) compared to manual fenestration (0.30 ± 0.10); this was not statistically significant (P = .069). It was technically difficult to fenestrate the disc spaces at L5-L6 and L6-L7 because of location and anatomy, resulting in a statistically significant increase in the median ratio of nuclear weight-to-volume ratios in both manual and VRD fenestration groups when compared to the more cranial L4-L5 disc spaces, 0.32 ± 0.08, and 0.35 ± 0.08 versus 0.25 ± 0.13 at L4-L5 (P = .026 and P = .004, respectively). CONCLUSIONS: The VRD is a feasible instrument for canine intervertebral disc fenestration. It is at least as effective as manual fenestration, and provides additional safety features.

Establishing an academic neurology specialty program: experiences over a five-year period.

Veterinary neurology is an expanding specialty field. At the time of this writing, 13 out of 33 (40%) US and Canadian veterinary colleges, and many more veterinary colleges outside of North America, had no active clinical neurology service. New academic programs will likely be established to fill this need, often starting with a single neurologist. Establishing a neurology service with one founding faculty member can be accomplished by developing the program in phases and creating a support network that optimizes faculty strengths and interests. Such an approach allows for the gradual expansion of services and staffing in a manageable way to ultimately provide a full-service program. A description of this development process at Purdue University School of Veterinary Medicine is presented as a case study and model for the establishment of other neurology or specialty services.

Brucella canis discospondylitis in 33 dogs.

Objective: To describe the clinical and imaging findings of 33 dogs with Brucella canis discospondylitis (BDS). Animals: 33 client owned dogs from four veterinary specialty hospitals within Colorado and Arizona with at least one positive B. canis test and spinal diagnostic imaging. Procedures: Retrospective review of signalment, physical and neurological examination findings, laboratory results, B. canis serology, and diagnostic imaging of 33 dogs with BDS. All imaging was reviewed by a board-certified veterinary neurologist. Radiographs were reviewed by a board-certified veterinary radiologist blinded to MRI and CT findings. Results: 31/33 (94%) dogs were <5 years old (median = 2.5 years, mean = 2.9 years, range 0.5-10 years). 21/29 (72%) dogs had signs of nonspecific pain, spinal pain, or lameness for >3 months (median = 6 months, mean = 8.2 months, range 5 days-4 years). Fever was seen in only 4/28 (14%) dogs. Multifocal lesions were evident on radiographs in 21/29 (72%) dogs and MRI in 12/18 (67%) dogs. Smooth, round, central end-plate lysis, defined as "hole punch" lesions, were identified radiographically in 25/29 (86%) dogs. Vertebral physitis or spondylitis without discitis was evident on MRI in 7/18 (39%) dogs. Clinical relevance: Dogs with BDS typically present at a young age with a long duration of clinical signs. Identification of radiographic "hole punch" lesions and MRI evidence of vertebral physitis, spondylitis, and paravertebral inflammation without discitis should increase suspicion for BDS. BDS may be increasing in frequency in the southwestern United States, and dogs with signs of chronic spinal pain and/or lameness should be screened for B. canis.

Reprogramming the Canine Glioma Microenvironment with Tumor Vaccination plus Oral Losartan and Propranolol Induces Objective Responses.

Purpose: Malignant gliomas have a highly immune suppressive tumor microenvironment (TME) which renders them largely unresponsive to conventional therapeutics. Therefore, the present study evaluated a therapeutic protocol designed overcome the immune barrier by combining myeloid cell targeted immunotherapy with tumor vaccination. Experimental Design: We utilized a spontaneously occurring canine glioma model to investigate an oral TME modifying immunotherapy in conjunction with cancer stem cell (CSC) vaccination. Dogs were treated daily with losartan (monocyte migration inhibitor) and propranolol (myeloid-derived suppressor cell depleting agent) plus anti-CSC vaccination on a bi-weekly then monthly schedule. Tumor volume was monitored by MRI and correlated with patient immune responses. Results: Ten dogs with histologically confirmed gliomas were enrolled into a prospective, open-label clinical trial to evaluate the immunotherapy protocol. Partial tumor regression was observed in 2 dogs, while 6 dogs experienced stable disease, for an overall clinical benefit rate of 80%. Overall survival times (median = 351 days) and progression-free intervals (median = 163 days) were comparable to prior studies evaluating surgical debulking followed by immunotherapy. Dogs with detectable anti-CSC antibody responses had an increased overall survival time relative to dogs that did not generate antibody responses (vaccine responder MST = 500 days; vaccine non-responder MST = 218 days; p = 0.02). Conclusions: These findings suggest that combining myeloid cell targeted oral immunotherapy with tumor vaccination can generate objective tumor responses, even in the absence of conventional therapy. Overall, this approach has promise as a readily implemented therapeutic strategy for use in brain cancer patients.

Evaluation of an acute focal epidural mass model to characterize the intracranial pressure-volume relationship in healthy Beagles.

OBJECTIVE: To characterize the intracranial pressure-volume relationship (ICPVR) in dogs by use of an acute frontal-parietal mass lesion model. ANIMALS: 7 healthy adult female Beagles. PROCEDURES: Dogs were anesthetized with isoflurane to achieve a surgical plane of anesthesia. A fiberoptic intracranial pressure (ICP) monitor was inserted to a depth of 1 cm in the parenchyma of the right frontal-parietal region of the brain. A Foley balloon-tipped catheter was placed in the epidural space of the left frontal-parietal area through a separate 1-cm burr hole. Baseline measurements were obtained with the balloon deflated. The balloon was then inflated incrementally with 0.5 mL of 0.9% NaCl solution every 10 minutes until ICP exceeded mean arterial blood pressure. Nonlinear regression analysis with 2-factor and 3-factor exponential equations was used to characterize the ICPVR. RESULTS: The mean baseline ICP was 11 mm Hg, with a 95% confidence interval of 2 to 20 mm Hg. The ICPVR was well characterized by 2-factor or 3-factor exponential equations for all dogs (R² > 0.93). Balloon volumes of > 1. 2 mL were associated with ICP > 20 mm Hg. CONCLUSIONS AND CLINICAL RELEVANCE: Characterization of the ICPVR may provide clinically useful information regarding the safety of obtaining CSF from the atlanto-occipital space or implantation of brachytherapy catheters and for determining the need for decompressive craniectomy in dogs with acute intracranial disease. High ICP should be suspected in dogs that have an acute frontal-parietal mass lesion estimated to exceed 2% of the brain volume.

Evaluation of minimally invasive excisional brain biopsy and intracranial brachytherapy catheter placement in dogs.

OBJECTIVE: To evaluate a technique for minimally invasive excisional brain biopsy and intracranial brachytherapy catheter placement in dogs. ANIMALS: 5 healthy adult female dogs. PROCEDURES: Computed tomographic guidance was used to plan a biopsy trajectory to a selected area of brain with reference to a localizer grid. The procedure was performed through a 1-cm skin incision and 6-mm burr hole by use of a 9-gauge biopsy device. Five cylindrical samples (3 to 4 mm in diameter and 7 to 12 mm in length) were removed over 5 cycles of the vacuum-assisted tissue excision system, leaving approximately a 2-cm³ resection cavity. A balloon-tipped intracranial brachytherapy catheter was placed through the burr hole into the resection cavity, expanded with saline (0.9% NaCl) solution, and explanted 7 days later. RESULTS: 4 of 5 dogs survived the procedure. The fifth died because of iatrogenic brain damage. Neurologic deficits were unilateral and focal. Twenty-four hours after surgery, all surviving dogs were ambulatory, 2 dogs exhibited ipsiversive circling, 4 had contralateral proprioceptive deficits, 3 had contralateral menace response deficits, 2 had a reduced contralateral response to noxious nasal stimulation, and 1 had dull mentation with intermittent horizontal nystagmus and ventrolateral strabismus. Neurologic status improved throughout the study period. Histologic quality of biopsy specimens was excellent. CONCLUSIONS AND CLINICAL RELEVANCE: This technique enabled histologic diagnosis from high-quality biopsy specimens obtained through a minimally invasive technique and has potential applications for multimodal treatment of deep brain tumors in dogs.

Use of Handheld Raman Spectroscopy for Intraoperative Differentiation of Normal Brain Tissue From Intracranial Neoplasms in Dogs.

The aim of this study was to assess feasibility and accuracy of a hand-held, intraoperative Raman spectroscopy device as a neuronavigation aid to accurately detect neoplastic tissue from adjacent normal gray and white matter. Although Raman spectra are complicated fingerprints of cell signature, the relative shift corresponding to lipid and protein content (2,845 and 2,930 cm-1, respectively), can provide a rapid assessment of whether tissue is normal white or gray matter vs. neoplasia for real-time guidance of tumor resection. Thirteen client-owned dogs were initially enrolled in the study. Two were excluded from final analysis due to incomplete data acquisition or lack of neoplastic disease. The diagnoses of the remaining 11 dogs included six meningiomas, two histiocytic sarcomas, and three gliomas. Intraoperatively, interrogated tissues included normal gray and/or white matter and tumor. A total of five Raman spectra readings were recorded from the interrogated tissues, and samples were submitted for confirmation of Raman spectra by histopathology. A resultant total of 24 samples, 13 from neoplastic tissue and 11 from normal gray or white matter, were used to calculate sensitivity and specificity of Raman spectra compared to histopathology. The handheld Raman spectroscopy device had sensitivity of 85.7% and specificity of 90% with a positive predictive value of 92.3% and negative predictive value of 81.6%. The Raman device was feasible to use intraoperatively with rapid interpretation of spectra. Raman spectroscopy may be useful for intraoperative guidance of tumor resection.

International veterinary canine dyskinesia task force ECVN consensus statement: Terminology and classification.

Movement disorders are a heterogeneous group of clinical syndromes in humans and animals characterized by involuntary movements without changes in consciousness. Canine movement disorders broadly include tremors, peripheral nerve hyperexcitability disorders, paroxysmal dyskinesia, and dystonia. Of these, canine paroxysmal dyskinesias remain one of the more difficult to identify and characterize in dogs. Canine paroxysmal dyskinesias include an array of movement disorders in which there is a recurrent episode of abnormal, involuntary, movement. In this consensus statement, we recommend standard terminology for describing the various movement disorders with an emphasis on paroxysmal dyskinesia, as well as a preliminary classification and clinical approach to reporting cases. In the clinical approach to movement disorders, we recommend categorizing movements into hyperkinetic vs hypokinetic, paroxysmal vs persistent, exercise-induced vs not related to exercise, using a detailed description of movements using the recommended terminology presented here, differentiating movement disorders vs other differential diagnoses, and then finally, determining whether the paroxysmal dyskinesia is due to either inherited or acquired etiologies. This consensus statement represents a starting point for consistent reporting of clinical descriptions and terminology associated with canine movement disorders, with additional focus on paroxysmal dyskinesia. With consistent reporting and identification of additional genetic mutations responsible for these disorders, our understanding of the phenotype, genotype, and pathophysiology will continue to develop and inform further modification of these recommendations.

A pilot study of optical neuronavigation-guided brain biopsy in the horse using anatomic landmarks and fiducial arrays for patient registration.

BACKGROUND: Optical neuronavigation-guided intracranial surgery has become increasingly common in veterinary medicine, but its use has not yet been described in horses. OBJECTIVES: To determine the feasibility of optical neuronavigation-guided intracranial biopsy procedures in the horse, compare the use of the standard fiducial array and anatomic landmarks for patient registration, and evaluate surgeon experience. ANIMALS: Six equine cadaver heads. METHODS: Computed tomography images of each specimen were acquired, with the fiducial array rigidly secured to the frontal bone. Six targets were selected in each specimen. Patient registration was performed separately for 3 targets using the fiducial array, and for 3 targets using anatomic landmarks. In lieu of biopsy, 1 mm diameter wire seeds were placed at each target. Postoperative images were coregistered with the planning scan to calculate Euclidian distance from the tip of the seed to the target. RESULTS: No statistical difference between registration techniques was identified. The impact of surgeon experience was examined for each technique using a Mann-Whitney U test. The experienced surgeon was significantly closer to the intended target (median = 2.52 mm) than were the novice surgeons (median = 6.55 mm) using the fiducial array (P = .001). Although not statistically significant (P = .31), for the experienced surgeon the median distance to target was similar when registering with the fiducial array (2.47 mm) and anatomic landmarks (2.58 mm). CONCLUSIONS AND CLINICAL IMPORTANCE: Registration using both fiducial arrays and anatomic landmarks for brain biopsy using optical neuronavigation in horses is feasible.

Comparative Molecular Life History of Spontaneous Canine and Human Gliomas.

Sporadic gliomas in companion dogs provide a window on the interaction between tumorigenic mechanisms and host environment. We compared the molecular profiles of canine gliomas with those of human pediatric and adult gliomas to characterize evolutionarily conserved mammalian mutational processes in gliomagenesis. Employing whole-genome, exome, transcriptome, and methylation sequencing of 83 canine gliomas, we found alterations shared between canine and human gliomas such as the receptor tyrosine kinases, TP53 and cell-cycle pathways, and IDH1 R132. Canine gliomas showed high similarity with human pediatric gliomas per robust aneuploidy, mutational rates, relative timing of mutations, and DNA-methylation patterns. Our cross-species comparative genomic analysis provides unique insights into glioma etiology and the chronology of glioma-causing somatic alterations.

Pregabalin as an adjunct to phenobarbital, potassium bromide, or a combination of phenobarbital and potassium bromide for treatment of dogs with suspected idiopathic epilepsy.

OBJECTIVE: To assess tolerability and short-term efficacy of oral administration of pregabalin as an adjunct to phenobarbital, potassium bromide, or a combination of phenobarbital and potassium bromide for treatment of dogs with poorly controlled suspected idiopathic epilepsy. DESIGN: Open-label, noncomparative clinical trial. ANIMALS: 11 client-owned dogs suspected of having idiopathic epilepsy that was inadequately controlled with phenobarbital, potassium bromide, or a combination of these 2 drugs. PROCEDURES: Dogs were treated with pregabalin (3 to 4 mg/kg [1.4 to 1.8 mg/lb], PO, q 8 h) for 3 months. Number of generalized seizures in the 3 months before and after initiation of pregabalin treatment was recorded. Number of responders (>or= 50% reduction in seizure frequency) was recorded, and seizure frequency before and after initiation of pregabalin treatment was compared by use of a nonparametric Wilcoxon signed rank test. RESULTS: Seizures were significantly reduced (mean, 57%; median, 50%) after pregabalin administration in the 9 dogs that completed the study; 7 were considered responders with mean and median seizure reductions of 64% and 58%, respectively. Adverse effects for pregabalin were reported in 10 dogs. Mean and median plasma pregabalin concentrations for all dogs were 6.4 and 7.3 microg/mL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Pregabalin may hold promise as a safe and effective adjunct anticonvulsant drug for epileptic dogs poorly controlled with the standard drugs phenobarbital or potassium bromide. Adverse effects of pregabalin appeared to be mild. Additional studies with larger numbers of dogs and longer follow-up intervals are warranted.

Randomized blinded controlled clinical trial to assess the effect of oral cannabidiol administration in addition to conventional antiepileptic treatment on seizure frequency in dogs with intractable idiopathic epilepsy.

OBJECTIVE: To assess the effect of oral cannabidiol (CBD) administration in addition to conventional antiepileptic treatment on seizure frequency in dogs with idiopathic epilepsy. DESIGN: Randomized blinded controlled clinical trial. ANIMALS: 26 client-owned dogs with intractable idiopathic epilepsy. PROCEDURES: Dogs were randomly assigned to a CBD (n = 12) or placebo (14) group. The CBD group received CBD-infused oil (2.5 mg/kg [1.1 mg/lb], PO) twice daily for 12 weeks in addition to existing antiepileptic treatments, and the placebo group received noninfused oil under the same conditions. Seizure activity, adverse effects, and plasma CBD concentrations were compared between groups. RESULTS: 2 dogs in the CBD group developed ataxia and were withdrawn from the study. After other exclusions, 9 dogs in the CBD group and 7 in the placebo group were included in the analysis. Dogs in the CBD group had a significant (median change, 33%) reduction in seizure frequency, compared with the placebo group. However, the proportion of dogs considered responders to treatment (≥ 50% decrease in seizure activity) was similar between groups. Plasma CBD concentrations were correlated with reduction in seizure frequency. Dogs in the CBD group had a significant increase in serum alkaline phosphatase activity. No adverse behavioral effects were reported by owners. CONCLUSIONS AND CLINICAL RELEVANCE: Although a significant reduction in seizure frequency was achieved for dogs in the CBD group, the proportion of responders was similar between groups. Given the correlation between plasma CBD concentration and seizure frequency, additional research is warranted to determine whether a higher dosage of CBD would be effective in reducing seizure activity by ≥ 50%.

Surgical decompression, with or without adjunctive therapy, for palliative treatment of primary vertebral osteosarcoma in dogs.

Vertebral osteosarcoma (OSA) is the most common primary vertebral tumor in dogs, however studies examining the survival time after surgical decompression of these tumors are limited. There is also limited information regarding the benefit of adjunctive treatments such as radiation therapy or chemotherapy in these patients. The goal of this study was to determine survival time of dogs with primary vertebral OSA after palliative decompressive surgery alone and combined with radiation therapy and/or chemotherapy. Records from 22 client-owned dogs diagnosed with primary vertebral OSA and treated with decompressive surgery were collected retrospectively from eight referral institutions. Survival time was assessed for dogs treated with surgery alone as well as dogs who received adjunctive radiation therapy and/or chemotherapy. Median survival time in the 12 dogs treated with surgery alone was 42 days (range: 3-1333 days). The three dogs treated with surgery and chemotherapy had a median survival time of 82 days (range: 56-305 days). Only one dog was treated with surgery and radiation therapy; this dog survived 101 days. Six dogs were treated with surgery, radiation therapy and chemotherapy; these dogs had a median survival time of 261 days (range: 223-653 days). Cause of death in all cases that survived the initial postoperative period was euthanasia secondary to confirmed or suspected tumor regrowth. The results of this study suggest that definitive radiation therapy, possibly combined with concurrent chemotherapy, significantly improves survival in dogs treated with palliative decompressive surgery for vertebral OSA and should be the treatment of choice in selected cases.

The effects of iatrogenic blood contamination on total nucleated cell counts and protein concentrations in canine cerebrospinal fluid.

BACKGROUND: Cerebrospinal fluid (CSF) might be altered by iatrogenic blood contamination, precluding accurate diagnostic interpretation. OBJECTIVES: Available formulas to correct for iatrogenic blood contamination are likely unreliable. Study objectives were to determine the effects of blood contamination on total nucleated cell counts (NCCs) and protein concentrations in canine CSF. METHODS: Two methods were followed to evaluate the effect of blood contamination on total NCC and protein concentrations in CSF. First, records from the Colorado State University Veterinary Teaching Hospital were retrospectively searched for dogs where CSF analysis was performed. Total NCCs, RBC counts, protein concentrations, and cytologic interpretations were recorded. Second, CSF from 4 canine patients and 3 research hounds was prospectively analyzed before and after known dilutions of whole blood were added. RESULTS: Of the 787 clinical samples analyzed, 108 samples had a cytologic diagnosis of blood contamination. RBC counts for all clinical samples ranged from 0 to 210,000 cells/µL. No correlation between total NCCs or protein concentrations with RBC counts were found when all samples were evaluated. Total NCCs and RBCs were weakly correlated in samples with a cytologic diagnosis of blood contamination and when ≥500 RBC/µL was present. When serial dilutions of whole blood were added to normal CSF, no significant changes were observed in the total NCCs of uncontaminated aliquots and contaminated aliquots containing up to 8480 RBC/µL. CONCLUSIONS: Erythrocyte counts in blood-contaminated canine CSF poorly correlate with total NCCs and protein concentrations. Using formulas to correct total NCCs and protein concentrations for the number of RBCs in CSF is inappropriate.

In vitro effect of chlorambucil on human glioma cell lines (SF767 and U87-MG), and human microvascular endothelial cell (HMVEC) and endothelial progenitor cells (ECFCs), in the context of plasma chlorambucil concentrations in tumor-bearing dogs.

The objective of this study was to investigate a possible mechanism of action of metronomic chlorambucil on glioma by studying the in vitro cytotoxicity and anti-angiogenic effects on glioma and endothelial cells, respectively. The in vitro LD50 and IC50 of chlorambucil were determined using human SF767 and U87-MG glioma cell lines, human microvascular endothelial cells (HMVECs) and human endothelial colony forming cells (ECFCs). Results were analyzed in the context of chlorambucil concentrations measured in the plasma of tumor-bearing dogs receiving 4 mg m-2 metronomic chlorambucil. The LD50 and IC50 of chlorambucil were 270 µM and 114 µM for SF767, and 390 µM and 96 µM for U87-MG, respectively. The IC50 of chlorambucil was 0.53 µM and 145 µM for the HMVECs and ECFCs, respectively. In pharmacokinetic studies, the mean plasma Cmax of chlorambucil was 0.06 µM. Results suggest that metronomic chlorambucil in dogs does not achieve plasma concentrations high enough to cause direct cytotoxic or growth inhibitory effects on either glioma or endothelial cells.