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Background: To ameliorate anticipated or ongoing neurological deficits, dogs undergoing brain tumor irradiation often are prescribed lengthy courses of prednisone PO during and after radiotherapy (RT). This practice can contribute to unwanted corticosteroid-associated morbidity and may be unnecessary., Objective: Determine whether long-term corticosteroid dependency can be minimized by use of succinct prednisone tapering., Animals: Fifty-five pet dogs undergoing brain tumor irradiation., Methods: Nineteen dogs were treated using a "rapid-taper" protocol wherein corticosteroid dose reduction began 0 to 20 days after completing RT. Outcomes were compared with a retrospectively studied control group ("slow-taper"; N = 36 dogs) in which corticosteroids were tapered more slowly according to individual clinician recommendations., Results: Patient demographics were similar between groups. Mean time to lowest prednisone dose was 41 days postirradiation in the rapid-taper group and 117 days in the slow-taper group (P = .003). In the rapid-taper group, 15 of 19 dogs (84%) were completely tapered off prednisone, vs 18 of 36 (50%) in the slow-taper group (P = .04). Rates at which corticosteroids had to be reinstituted later were similar for the 2 groups (approximately 1 in 3 dogs). Adverse effect rates were similar for the 2 groups. Although no comparable questionnaire-derived data were available for the "slow-taper" group, overall and neurologic quality of life remained stable after RT in the rapid-taper group., Conclusions and Clinical Importance: For many dogs, lengthy courses of PO prednisone are avoidable after intracranial RT. Future efforts should aim to identify which dogs benefit most from accelerated prednisone tapering., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Pituitary apoplexy refers to hemorrhage or infarction within the pituitary gland resulting in acute neurological abnormalities. This condition is poorly described in dogs., Objectives: To document presenting complaints, examination findings, endocrinopathies, magnetic resonance imaging (MRI), treatments, and outcomes of dogs with pituitary apoplexy., Animals: Twenty-six client-owned dogs with acute onset of neurological dysfunction., Methods: Retrospective case series. Dogs were diagnosed with pituitary apoplexy if MRI or histopathology documented an intrasellar or suprasellar mass with evidence of hemorrhage or infarction in conjunction with acute neurological dysfunction. Clinical information was obtained from medical records and imaging reports., Results: Common presenting complaints included altered mentation (16/26, 62%) and gastrointestinal dysfunction (14/26, 54%). Gait or posture changes (22/26, 85%), mentation changes (18/26, 69%), cranial neuropathies (17/26, 65%), cervical or head hyperpathia (12/26, 46%), and hyperthermia (8/26, 31%) were the most frequent exam findings. Ten dogs (38%) lacked evidence of an endocrinopathy before presentation. Common MRI findings included T1-weighted hypo- to isointensity of the hemorrhagic lesion (21/25, 84%), peripheral enhancement of the pituitary mass lesion (15/25, 60%), brain herniation (14/25, 56%), and obstructive hydrocephalus (13/25, 52%). Fifteen dogs (58%) survived to hospital discharge. Seven of these dogs received medical management alone (median survival 143 days; range, 7-641 days) and 8 received medications and radiation therapy (median survival 973 days; range, 41-1719 days)., Conclusions and Clinical Importance: Dogs with pituitary apoplexy present with a variety of acute signs of neurological disease and inconsistent endocrine dysfunction. Dogs that survive to discharge can have a favorable outcome., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Improved understanding of Bartonella spp. serology in dogs may aid clinical decision making., Objective: Describe demographic and geographic patterns of Bartonella spp. seroreactivity in dogs, and describe hematologic and serum biochemical abnormalities in Bartonella spp. seroreactive and nonseroreactive dogs., Animals: Serum samples from 5957 dogs in the United States, previously submitted to IDEXX Reference Laboratories., Methods: Serum was tested using 3 indirect ELISAs for B. henselae, B. vinsonii subsp. berkhoffii, and B. koehlerae. Complete blood count and serum biochemistry panel results were reviewed retrospectively., Results: Overall, 6.1% of dogs were Bartonella spp. seroreactive. Toy breeds were less likely to be seroreactive (3.9%) than mixed breeds (7.5%; adjusted odds ratio [aOR], 0.48; 95% confidence interval [CI], 0.32-0.72), and dogs <1 year old were less likely to be seroreactive (3.4%) than dogs 1 to 5.5 years of age (7.3%; aOR, 0.42; 95% CI, 0.23-0.72). Dogs in the West South Central (9.8%) and South Atlantic (8.8%) regions were more likely than dogs elsewhere in the United States to be seroreactive (aOR, 2.22; 95% CI, 1.31-3.87; aOR, 2.44; 95% CI, 1.38-4.36)., Conclusions and Clinical Importance: Demographic and geographic findings for Bartonella spp. exposure were broadly comparable to previously reported patterns., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Vascular endothelial growth factor (VEGF) is a key molecular driver of angiogenesis and vascular permeability and is expressed by a wide variety of neoplasms. Although blood VEGF concentrations have been quantified in intracranial tumors of dogs, cerebrospinal fluid (CSF) VEGF concentration might be a more sensitive biomarker of disease., Objective: Concentrations of VEGF in CSF are higher in dogs with central nervous system (CNS) neoplasia compared to those with meningoencephalomyelitis and other neurologic disorders., Animals: One hundred and twenty-six client-owned dogs presented to a veterinary teaching hospital., Methods: Case-control study. Cerebrospinal fluid was archived from dogs diagnosed with CNS neoplasia and meningoencephalomyelitis. Control dogs had other neurological disorders or diseases outside of the CNS. A commercially available kit was used to determine VEGF concentrations., Results: Detectable CSF VEGF concentrations were present in 49/63 (77.8%) neoplastic samples, 22/24 (91.7%) inflammatory samples, and 8/39 (20.5%) control samples. The VEGF concentrations were significantly different between groups (P < .0001), and multiple comparison testing showed that both neoplastic and inflammatory groups had significantly higher concentrations than did controls (P < .05), but did not differ from each other. Gliomas and choroid plexus tumors had significantly higher VEGF concentrations than did the control group (P < .05)., Conclusions and Clinical Importance: Cerebrospinal fluid VEGF concentrations may serve as a marker of neoplastic and inflammatory CNS disorders relative to other conditions., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

An 18-month-old intact male Schnauzer dog was evaluated for chronic, lifelong respiratory tract infections that were unresponsive to administration of a variety of antibiotics and corticosteroids. The dog developed persistent vomiting and diarrhea around 1 year of age that was minimally responsive to diet change, antibiotics, and corticosteroids. Despite supportive care, the dog was ultimately euthanized at 20 months of age due to persistent respiratory and gastrointestinal disease. Whole genome sequencing discovered a deleterious missense A/C mutation within the NAT10 gene, a gene essential for microtubule acetylation, appropriate ciliary development, and cytokinesis. Pipeline analysis of the genomes of 579 dogs from 55 breeds did not detect this mutation. Though never described in veterinary medicine, NAT10 mutation occurs in humans with ciliary aplasia, suggesting a pathophysiological mechanism for this dog and highlighting an associated mutation or possible novel genetic cause of chronic respiratory infections in dogs., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Little is known regarding the comparative efficacy of various irradiation strategies used to treat intranasal carcinomas (INC) in cats., Objectives: Investigate outcomes and prognostic factors associated with survival for cats with INC., Animals: Forty-two cats with INC that underwent radiotherapy (RT)., Methods: Single-arm retrospective study. Medical record review for cats with INC that underwent RT at 1 of 7 veterinary RT facilities. Irradiation protocols categorized as: definitive-intent fractionated RT (FRT), definitive-intent stereotactic RT (SRT), and palliative-intent RT (PRT). Median overall survival time (OST) and disease progression-free survival (PFS; documented by advanced transverse imaging, or recurrence of symptoms) were calculated. Associations between tumor stage, RT protocol/intent, and adjunctive treatment usage and outcome were calculated., Results: Cats underwent SRT (N = 18), FRT (N = 8), and PRT (N = 16). In multivariate modeling, cats received definitive-intent treatment (DRT; FRT/SRT) had significantly longer median PFS (504 days, [95% confidence interval (CI): 428-580 days] vs PRT 198 days [95% CI: 62-334 days]; p = 0.006) and median OST [721 days (95% CI: 527-915 days) vs 284 days (95% CI: 0-570 days); p = 0.001]). Cats that underwent second DRT course at time of recurrence lived significantly longer than cats that received 1 RT course (either DRT or PRT [median OST 824 days (95% CI: 237-1410 days) vs 434 days (95% CI: 277-591 days); p = .028])., Conclusion: In cats with INC, DRT is associated with prolonged OST and PFS as compared to PRT. If tumor progression occurs, a second course of DRT should be considered., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Locoregional tumor control and prolonged survival for dogs with genitourinary carcinoma (CGUC) reportedly are achievable using treatment with radiotherapy (RT) with or without adjunctive chemotherapy and nonsteroidal anti-inflammatory drugs (NSAIDs)., Objectives: To characterize event-free and overall survival after treatment of CGUC using NSAIDs, mitoxantrone (MTX), and a standardized RT protocol (57 Gy in 20 fractions)., Animals: Fifty-one client-owned dogs treated between 2008 and 2017., Methods: Dogs were retrospectively categorized into treatment groups: (a) first-line concurrent chemoradiotherapy (≥1 dose of MTX started within 1 month of RT); (b) first-line chemotherapy (MTX administered for >1 month before RT without tumor progression); (c) RT as a salvage procedure (MTX, surgery or both with subsequent locoregional tumor progression before RT). Treatment-induced toxicoses, event-free survival (EFS), and overall survival times (OSTs) were recorded. The influence of demographics, staging, and treatment-related factors on survival was assessed using Cox proportional hazards modeling., Results: Median EFS and OST for all dogs were 260 and 510 days with no significant differences among groups 1 (n = 39), 2 (n = 4), and 3 (n = 8). Both EFS and OST were shorter in dogs with moderate to severe clinical signs (P < .001 and P < .001, respectively); OST was shorter in dogs with prostatic involvement (P = .02). Permanent urinary incontinence developed in 16 dogs (31%) at a median of 70 days postirradiation; other toxicoses were mild and self-limiting., Conclusions and Clinical Importance: Mild clinical signs and lack of prostate involvement were associated with favorable prognosis for survival. Client education regarding the risk of urinary incontinence is warranted., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

Background: Lumbar syringomyelia (SM), lumbosacral pain, and more caudal spinal cord termination are reported in Cavalier King Charles spaniels (CKCS). Data are lacking on the clinical relevance of alterations in their spinal cord terminal structures., Objectives: To compare spinal cord termination level and filum terminale internum length (FTIL) with presence of lumbar SM and clinical signs in CKCS., Animals: Forty-eight CKCS., Methods: In this prospective study, pain was quantified using owner and clinician assessments. Vertebral level of spinal cord and dural sac termination, presence of SM, and FTIL were determined from sagittal magnetic resonance imaging (MRI) sequences. Kappa and intraclass correlation (ICC) analyses determined interobserver reliability. The MRI findings were compared to owner and clinician-reported pain quantification., Results: Interobserver reliability was good for spinal cord and dural sac termination (kappa = 0.61 and 0.64, respectively) and excellent for FTIL (ICC: 92% agreement). The spinal cord terminated at 6th lumbar vertebra in 1, 7th lumbar vertebra in 31, and the sacrum in 15 dogs, and termination level was associated with lumbar SM (P = .002) but not clinical signs. Mean FTIL was 2.9 ± 1.08 mm; it was associated with owner-reported pain (P = .033) and spinal palpation scores (P = .023). Painful CKCS without SM had shorter FTIL compared to normal CKCS and painful CKCS with SM (P = .02)., Conclusions: Painful CKCS without SM have decreased distance between the termination of the spinal cord and dural sac, suggesting a shorter FTIL. More caudal spinal cord termination is associated with development of lumbar SM., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

Background: Cerebrospinal fluid (CSF) lactate concentrations increase after seizure activity in many human patients independent of the underlying disease process. The effect of seizure activity on CSF lactate concentration in dogs is unknown., Hypothesis/objectives: Cerebrospinal fluid lactate concentration is unaffected by seizure activity in dogs and is more dependent on the underlying disease process causing the seizures., Animals: One-hundred eighteen client-owned dogs with seizure disorders., Methods: Case series. Cerebrospinal fluid lactate concentration was determined using a commercially available lactate monitor. Seizure semiology, time from last seizure to CSF collection, number of seizures within the 72 hours preceding CSF collection, and clinical diagnosis were recorded., Results: Dogs with focal seizures had higher CSF lactate concentrations than did those with generalized seizures (P = .03). No differences in lactate concentrations were found among dogs with single seizures, cluster seizures or status epilepticus (P = .12), among dogs with CSF collection at different time points after the last seizure activity (P = .39) or among dogs having different numbers of seizures within the 72 hours preceding CSF collection (P = .42). A significant difference (P = .001) was found in CSF lactate concentrations among diagnostic groups, and dogs with inflammatory and neoplastic disease had higher concentrations than did dogs with idiopathic or unknown epilepsy., Conclusions and Clinical Importance: Cerebrospinal fluid lactate concentration is minimally affected by seizure activity in dogs and increased concentrations are more likely associated with the underlying disease process., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Bartonella spp. comprise a genus of bacteria that frequently cause persistent, often subclinical infection. Although many Bartonella spp. have been implicated in a variety of clinical presentations, Bartonella rochalimae has yet to be documented in association with a clinical presentation other than infectious endocarditis (IE) in dogs., Objectives: To document a spectrum of clinical presentations accompanied by mild hematological abnormalities in B rochalimae-infected dogs from the United States., Animals: Eight dogs with documented B rochalimae infection., Methods: Retrospective 10-year study of B rochalimae naturally infected dogs. Clinical and clinicopathologic data, including medical history, CBC, serum biochemistry panel, urinalysis, echocardiogram, and comprehensive vector-borne disease diagnostic panel results, were reviewed., Results: Eight dogs were diagnosed with B rochalimae via polymerase chain reaction (PCR) amplification. Five dogs were diagnosed with IE. Three dogs, PCR positive for B rochalimae, were diagnosed with seizures or antibiotic responsive lameness or during routine screening of a military working dog., Conclusions: This case series provides support for an association between B rochalimae and IE and provides documentation of dogs infected with B rochalimae with other clinical diagnoses., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Chronic neuropathic pain is a common complication in people with spinal cord injury (SCI) but has not been investigated in dogs., Objective: To determine the reliability of measuring spinal mechanical sensory thresholds (MSTs) in dogs and to compare MSTs of healthy dogs and dogs with SCI caused by acute thoracolumbar intervertebral disk extrusion after hemilaminectomy over a 1-year period., Study Design: Prospective study., Animals: Thirty-two healthy and 40 SCI dogs., Methods: Dogs were divided into group 1 (healthy Dachshunds), group 2 (healthy dogs including several breeds), and SCI group. The MSTs were measured using algometry at an incision (thoracolumbar) and control site. Dogs in group 1 were tested once; those in group 2 were tested for 5 consecutive days; and SCI dogs were tested on days 7, 14, 28, 42, 180, and 365 postoperatively. The MSTs were compared among days in healthy and SCI dogs and between SCI and healthy dogs using mixed effect models. P < .05 was considered significant., Results: At the incision site of SCI dogs, MST was significantly lower than in healthy dogs for 42 days postoperatively, but not subsequently. However, 4/27 dogs had control site MST below the reference range 1 year after surgery., Conclusions and Clinical Importance: Mechanical sensory thresholds normalize by 6 months after surgery in most dogs with SCI. Approximately 15% of SCI dogs may develop chronic neuropathic pain. Improving long-term pain assessment of SCI dogs is important for offering treatment options and advising owners., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Procalcitonin (PCT) is an important biomarker for sepsis in human medicine, but there is little information regarding PCT as a biomarker for sepsis in dogs. There are no controlled studies evaluating serial concentrations of PCT in dogs., Hypothesis/objective: That PCT would be rapidly detectable in serum after injection of LPS and would remain increased for at least 24 hours. Objective was to evaluate serial serum PCT concentrations in dogs after a single IV injection of LPS compared to placebo., Animals: Six healthy mixed breed dogs., Methods: A nonrandomized, placebo-controlled, crossover study was performed. Dogs were initially injected with placebo (0.9% NaCl; 1 mL, IV) and then experimental endotoxemia was induced by injecting lipopolysaccharide (LPS; 2 μg/kg, IV, once) after a 5-day washout period. Serial blood samples were collected for measurement of serum PCT after each injection. Difference in median PCT concentration between serial time points was assessed using a mixed effects model., Results: After LPS administration, blood pressure decreased and body temperature increased along with the development of lethargy, vomiting, and diarrhea. Procalcitonin was significantly increased compared to baseline by 2 hours after injection of LPS (median = 67.9 versus 172.8, range = 46.0-74.1 versus 99.5-295.9, P = .0002) and remained significantly increased for 12 hours (median = 205.9, range = 119.9-297.4) with return to baseline by 48 hours. Procalcitonin was significantly higher than placebo 2, 4, 6, 8, 10, 12, and 24 hours after injection. There were no significant differences in PCT between time 0 and any of the subsequent time points in the saline group., Conclusions and Clinical Importance: Procalcitonin expression is likely to be a clinically useful biomarker for sepsis in dogs and might have an additional role in prognostication and therapeutic decision-making., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Dynamics of infection by Bartonella and Rickettsia species, which are epidemiologically associated in dogs, have not been explored in a controlled setting., Objectives: Describe an outbreak investigation of occult Bartonella spp. infection among a group of dogs, discovered after experimentally induced Rickettsia rickettsii (Rr) infection., Animals: Six apparently healthy purpose-bred Beagles obtained from a commercial vendor., Methods: Retrospective and prospective study. Dogs were serially tested for Bartonella spp. and Rr using serology, culture, and PCR, over 3 study phases: 3 months before inoculation with Rr (retrospective), 6 weeks after inoculation with Rr (retrospective), and 8 months of follow-up (prospective)., Results: Before Rr infection, 1 dog was Bartonella henselae (Bh) immunofluorescent antibody assay (IFA) seroreactive and 1 was Rickettsia spp. IFA seroreactive. After inoculation with Rr, all dogs developed mild Rocky Mountain spotted fever compatible with low-dose Rr infection, seroconverted to Rickettsia spp. within 4-11 days, and recovered within 1 week. When 1 dog developed ear tip vasculitis with intra-lesional Bh, an investigation of Bartonella spp. infection was undertaken. All dogs had seroconverted to 1-3 Bartonella spp. between 7 and 18 days after Rr inoculation. Between 4 and 8 months after Rr inoculation, Bh DNA was amplified from multiple tissues from 2 dogs, and Bartonella vinsonii subsp. berkhoffii (Bvb) DNA was amplified from 4 of 5 dogs' oral swabs., Conclusions and Clinical Importance: Vector-borne disease exposure was demonstrated in research dogs from a commercial vendor. Despite limitations, our results support the possibilities of recrudescence of chronic subclinical Bartonella spp. infection after Rr infection and horizontal direct-contact transmission between dogs., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Cerebrospinal fluid (CSF) lactate is frequently used as a biomarker in humans with inflammatory central nervous system (CNS) disorders including bacterial meningitis and autoimmune disorders such as multiple sclerosis., Hypothesis: Cerebrospinal fluid lactate concentrations are increased in a subset of dogs with inflammatory CNS disorders., Animals: One hundred two client-owned dogs diagnosed with inflammatory CNS disease., Methods: Case series. Cases were identified both prospectively at the time of diagnosis and retrospectively by review of a CSF biorepository. Cerebrospinal fluid lactate was analyzed with a commercially available, handheld lactate monitor. Subcategories of inflammatory disease were created for comparison (eg, steroid-responsive meningitis arteritis, meningoencephalitis of unknown etiology)., Results: Cerebrospinal fluid lactate concentrations were above reference range in 47% of dogs (median, 2.5 mmol/L; range, 1.0-11.7 mmol/L). There was no significant difference in lactate concentrations between disease subcategories (P = .48). Significant but weak correlations were noted between CSF lactate concentration and nucleated cell count (r = .33, P < .001), absolute large mononuclear cell count (r = .44, P < .001), absolute small mononuclear cell count (r = .39, P < .001), absolute neutrophil cell count (r = .24, P = .01), and protein (r = .44, P < .001). No correlation was found between CSF lactate concentration and CSF red blood cell count (P = .58). There was no significant association of CSF lactate concentration with survival (P = .27)., Conclusions and Clinical Importance: Cerebrospinal fluid lactate concentrations could serve as a rapid biomarker of inflammatory CNS disease in dogs., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Babesiosis is an important cause of thrombocytopenia and hemolytic anemia in dogs. Babesia vulpes, reported in European dogs and North American foxes, rarely has been reported in domestic North American dogs. Newly optimized polymerase chain reaction (PCR) primers facilitate more sensitive amplification of B. vulpes DNA., Objectives: To determine the prevalence of Babesia sp. infections in dogs being tested for Babesia infection, and to describe co-infections and clinicopathologic abnormalities in B. vulpes positive dogs., Animals: Dog blood or tissue samples (n = 9367) submitted to a diagnostic laboratory between June 2015 and June 2018 were tested using an optimized Babesia PCR assay., Methods: Comprehensive canine vector-borne disease diagnostic testing was performed on convenience samples., Results: Babesia sp. DNA was amplified from 269/9367 (2.9%) North American dogs. Babesia sp. infections included B. gibsoni monoinfection (157; 1.7%), B. vulpes monoinfection (19; 0.20%), and B. gibsoni and B. vulpes coinfection (29; 0.31%). Forty-three of the 48 total B. vulpes-infected dogs were American Pit Bull Terrier-type breeds, of which 36 historically were involved with dog fights. Coinfections with Mycoplasma, Dirofilaria immitis, or Wolbachia and coexposures to Bartonella, Ehrlichia, and Rickettsia spp. were documented in B. vulpes-infected dogs. Clinicopathologic data in B. vulpes-infected dogs both with and without coinfections included anemia, thrombocytopenia, hyperglobulinemia, hypoalbuminemia, and proteinuria., Conclusions and Clinical Importance: Babesia vulpes infection in domestic North American dogs is commonly found in conjunction with other coinfections, including B. gibsoni and hemotropic Mycoplasma. Similar to B. gibsoni, dog-to-dog transmission of B. vulpes may be a frequent mode of transmission., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Presumed autoimmune diseases affecting the central nervous system (CNS) of dogs are common. In people, antibodies against neuronal cell surface antigens that are associated with a wide variety of neurological syndromes have been identified. The presence of cerebrospinal fluid (CSF) autoantibodies that target neuronal cell surface proteins has not been reported in dogs with neurologic disorders., Objectives: Autoantibodies to neuronal cell surface antigens can be found in the CSF of dogs with inflammatory CNS disease. Our aim was to determine whether 6 neuronal cell surface autoantibodies were present in the CSF of dogs diagnosed with inflammatory and noninflammatory CNS disease., Animals: Client-owned dogs with CNS disease and complete diagnostic evaluation including magnetic resonance imaging and CSF analysis were included. One healthy dog was included as a negative control., Methods: Cerebrospinal fluid was tested for 6 antigenic targets with a commercially available indirect immunofluorescence assay test kit., Results: There were 32 dogs with neurological disease, 19 diagnosed with inflammatory disease (encephalitis and meningitis), 10 with noninflammatory disease (neoplasia, intervertebral disk disease, degenerative myelopathy, and epilepsy), 2 with no diagnosis, and 1 with neoplasia and meningoencephalitis. Anti-N-methyl-d-aspartate receptor 1 (NMDAR1) antibodies were detected in 3 dogs (3/32; 9.38%). All 3 dogs responded to treatment of meningoencephalomyelitis of unknown etiology (MUE)., Conclusions and Clinical Importance: Further evaluation of the prevalence and clinical relevance of CSF and serum antibodies to neuronal cell surface antigens is warranted. Defining antigenic targets associated with encephalitis in dogs might allow diagnostic categorization of MUE antemortem., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Ehrlichia ewingii is the most seroprevalent Ehrlichia-infecting dogs in the southern and mid-western United States. Fever, lameness, and polyarthritis are commonly reported findings in dogs naturally infected with E. ewingii., Objectives: To evaluate clinicopathologic findings in a population of dogs naturally infected with E. ewingii., Animals: Forty-one dogs PCR positive for E. ewingii and PCR negative for other targeted vector-borne organisms., Methods: Retrospective study. Clinical and clinicopathologic data including physical examination findings, CBC, serum biochemistry, urinalysis (UA), symmetric dimethylarginine (SDMA), and vector-borne disease diagnostic results were reviewed., Results: Frequent clinical diagnoses other than ehrlichiosis (28/41; 68.3%) were renal disease (7/41; 17.1%) and immune-mediated hemolytic anemia (IMHA) (6/41; 14.6%). The most frequent physical examination finding was joint pain (14/41; 34.1%). Prominent hematologic and biochemical abnormalities included abnormal lymphocyte counts (22/36; 61.1%); neutrophilia (21/37; 56.8%); increased alkaline phosphatase (20/35; 57.1%) and alanine transaminase (14/35; 40%) activities; and increased SDMA concentration (11/34; 32.4%). Urinalysis abnormalities included proteinuria (20/27; 74%), most with inactive sediments (16/20; 80%). Dogs were seroreactive by Ehrlichia canis immunofluorescence assay (IFA; 17/39; 43.6%) and Ehrlichia ELISA (34/41; 82.9%). Seroreactivity by IFA for other vector-borne pathogens included Bartonella (1/39; 2.6%), Rickettsia rickettsii (spotted-fever group rickettsiae) (12/39; 30.8%), and Borrelia burgdorferi by ELISA (1/41; 2.4%)., Conclusions and Clinical Importance: Renal disease, IMHA, proteinuria, neutrophilia, abnormal lymphocytes, and increased liver enzyme activities were common in this group of E. ewingii-infected dogs. Studies are needed to determine if E. ewingii contributes to comorbidities or is a precipitating factor in clinical syndromes in persistently infected dogs., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: A noninvasive biomarker is needed to predict recovery from severe spinal cord injury (SCI) because of thoracolumbar intervertebral disc extrusion (TL-IVDE). Proteins released from neural and glial cells can be detected in the blood and show promise as prognostic tools, but their concentration is influenced by time after injury., Hypothesis/objectives: Serum concentrations of glial fibrillary acidic protein (GFAP), phosphorylated neurofilament heavy chain (pNFH), and S100β will follow different time courses; measurement of combinations of these proteins will predict outcome., Animals: Thirty-one dogs with TL-IVDE causing paralysis with no pain perception., Methods: Prospective study. Serum samples were taken at presentation and intervals over 56 days and banked at -80°C. Glial fibrillary acidic protein, pNFH, and S100β concentrations were measured using ELISA tests and plotted against time from onset of nonambulatory status. Outcome was established at 6 months. The association between biomarker concentration and outcome was examined using logistic regression, receiver operator characteristics curve analysis, and model development., Results: Thirty-one dogs participated, 3/31 (10%) developed progressive myelomalacia and 19/31 (62%) recovered ambulation. Glial fibrillary acidic protein and S100β concentrations rose for the first 1 to 3 days, and were undetectable by 14 and 28 days, respectively. Phosphorylated neurofilament heavy chain concentrations peaked at 14 days and were detectable at 56 days. Glial fibrillary acidic protein concentrations in the first 72 hours after onset of nonambulatory status predicted recovery with an accuracy of 76.7%-89% depending on sample timing., Conclusions and Clinical Importance: Serum GFAP concentrations can be used to predict outcome in clinically complete SCI. A rapid inexpensive bedside test is needed., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: There is an association between Chiari malformations, syringomyelia (CMSM) and tethered cord syndrome (TCS) in people, suggesting Cavalier King Charles Spaniels (CKCS) with CMSM could also have TCS. Currently there are no data on the position of the caudal spinal cord structures in CKCS., Objective: To describe and compare location of spinal cord termination in CKCS with weight-matched controls and to examine the relationship between SM and spinal cord termination., Animals: Thirty-nine CKCS and 33 controls with thoracolumbar MRIs; 34 of 39 CKCS also had cervical MRIs., Methods: Blinded retrospective study. Spinal cord and dural sac termination were determined from T2-weighted sagittal and transverse images and half-Fourier acquisition single-shot turbo spin echo sequences. Intra-observer reliability was determined using kappa analysis. Presence of SM was compared with location of spinal cord and dural sac termination., Results: Intra-observer reliability was moderate for identifying spinal cord termination (Kappa = 0.6) and good for dural sac termination (Kappa = 0.8). The spinal cord terminated at lumbar vertebra 6 (L6) in 1, 7 (L7) in 22, and sacrum in 16 CKCS versus 9 at L6, 23 at L7, 1 at sacrum in controls. Spinal cord (P < .001) and dural sac (P = .002) termination were significantly more caudal in CKCS compared to controls. The presence of thoracolumbar SM was associated with more caudal dural sac termination in CKCS (P = .03)., Conclusions and Clinical Importance: The relationship between TL SM and possible spinal cord tethering because of a more caudal dural sac termination should be investigated., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Cavalier King Charles Spaniels (CKCS) suffer pain associated with Chiari-like malformation and syringomyelia (CMSM). People suffer from a similar condition and describe numerous sensory abnormalities. Sensory changes have not been quantified in affected CKCS., Objectives: To use quantitative sensory testing (QST) to quantify thermal and mechanical thresholds in CKCS and to compare QST in dogs with and without syringomyelia (SM)., Animals: Forty-four CKCS., Methods: Prospective study. Dogs underwent neurological examinations and craniocervical magnetic resonance imaging (MRI). Thermal testing was performed over the humerus and thorax (n = 32); mechanical testing was performed on the paw and neck (n = 44). Latencies, thresholds, and response rates were compared with presence and severity of SM on MRI, presence of pain reported by the owner and pain identified on examination., Results: Thirty dogs had SM, 30 were painful on examination, 29 were owner-reported symptomatic. Thermal and mechanical variables were not significantly different based on presence or severity of SM. Dogs with pain on examination had decreased mechanical thresholds on the paw (0.38 kg, SD = 0.18) and neck (2.05 kg, SD = 0.74) compared to thresholds of dogs without pain on examination on the paw (0.60 kg, SD = 0.30) and neck (2.72 kg, SD = 0.57; P = .021)., Conclusions and Clinical Importance: Mechanical and thermal sensitivity does not appear to be related to the presence of SM, but mechanical sensitivity appears to be related to the presence of pain and clinical signs. Mechanical testing may be useful for assessing sensory abnormalities during clinical trials., (© 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Gabapentin is the most commonly prescribed medication for the treatment of chronic musculoskeletal pain in cats. Despite this common and chronic usage, clinically relevant pharmacokinetic data is lacking., Objectives: To evaluate the pharmacokinetics of clinically relevant dosing regimens of gabapentin in cats., Animals: Eight research-purpose mixed-breed cats., Methods: Cats were enrolled in a serial order, non-randomized pharmacokinetic study. Gabapentin was administered as an IV bolus (5 mg/kg), orally (10 mg/kg) as a single dose or twice daily for 2 weeks, or as a transdermal gel (10 mg/kg) in serial order. Serial blood samples were collected up to 48 hours. Plasma concentrations were determined using Ultra Performance Liquid Chromatography-Mass Spectrometry. Compartmental analysis was used to generate gabapentin time-concentration models., Results: After IV administration CL (median (range)) and terminal half-life were 160.67 mL/kg*hr (119.63-199.11) and 3.78 hours (3.12-4.47), respectively. The oral terminal half-life was 3.63 hours (2.96-4.77), and 3.72 hours (3.12-4.51) for single and repeated dosing. T MAX and C MAX , as predicted by the model were 1.05 hours (0.74-2.11), and 12.42 μg/mL (8.31-18.35) after single oral dosing, and 0.77 hours (0.58-1.64), and 14.78 μg/mL (9.70-18.41) after repeated oral dosing. Bioavailability after a single oral dose was 94.77% (82.46-122.83)., Importance: Repeated oral dosing of gabapentin did not alter the drug's pharmacokinetics, making dose adjustments unnecessary with long-term treatment. As prepared, the transdermal route is an inappropriate choice for drug administration. These relevant data are important for future studies evaluating potential efficacy of the medication for treating chronic pain states in cats., (© 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Experimental evidence shows benefit of rehabilitation after spinal cord injury (SCI) but there are limited objective data on the effect of rehabilitation on recovery of dogs after surgery for acute thoracolumbar intervertebral disc herniations (TL-IVDH)., Objective: Compare the effect of basic and intensive post-operative rehabilitation programs on recovery of locomotion in dogs with acute TL-IVDH in a randomized, blinded, prospective clinical trial., Animals: Thirty non-ambulatory paraparetic or paraplegic (with pain perception) dogs after decompressive surgery for TL-IVDH., Methods: Blinded, prospective clinical trial. Dogs were randomized (1:1) to a basic or intensive 14-day in-house rehabilitation protocol. Fourteen-day open field gait score (OFS) and coordination (regulatory index, RI) were primary outcomes. Secondary measures of gait, post-operative pain, and weight were compared at 14 and 42 days., Results: Of 50 dogs assessed, 32 met inclusion criteria and 30 completed the protocol. There were no adverse events associated with rehabilitation. Median time to walking was 7.5 (2 - 37) days. Mean change in OFS by day 14 was 6.13 (confidence intervals: 4.88, 7.39, basic) versus 5.73 (4.94, 6.53, intensive) representing a treatment effect of -0.4 (-1.82, 1.02) which was not significant, P=.57. RI on day 14 was 55.13 (36.88, 73.38, basic) versus 51.65 (30.98, 72.33, intensive), a non-significant treatment effect of -3.47 (-29.81, 22.87), P = .79. There were no differences in secondary outcomes between groups., Conclusions: Early postoperative rehabilitation after surgery for TL-IVDH is safe but doesn't improve rate or level of recovery in dogs with incomplete SCI., (Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: We aimed to identify mutations associated with osteochondromatosis in a litter of American Staffordshire Terrier puppies., Hypothesis: We hypothesized that the associated mutation would be located in a gene that causes osteochondromatosis in humans., Animals: A litter of 9 American Staffordshire puppies, their sire and dam, 3 of 4 grandparents, 26 healthy unrelated American Staffordshire Terriers, and 154 dogs of 27 different breeds., Methods: Whole genome sequencing was performed on the proband, and variants were compared against polymorphisms derived from 154 additional dogs across 27 breeds, as well as single nucleotide polymorphism database 146. One variant was selected for follow-up sequencing. Parentage and genetic mosaicism were evaluated across the litter., Results: We found 56,301 genetic variants unique to the proband. Eleven variants were located in or near the gene exostosin 2 (EXT2), which is strongly associated with osteochondromatosis in humans. One heterozygous variant (c.969C > A) is predicted to result in a stop codon in exon 5 of the gene. Sanger sequencing identified the identical mutation in all affected offspring. The mutation was absent in the unaffected offspring, both parents, all available grandparents, and 26 healthy unrelated American Staffordshire Terriers., Conclusions and Clinical Importance: These findings represent the first reported mutation associated with osteochondromatosis in dogs. Because this mutation arose de novo, the identical mutation is unlikely to be the cause of osteochondromatosis in other dogs. However, de novo mutations in EXT2 are common in humans with osteochondromatosis, and by extension, it is possible that dogs with osteochondromatosis could be identified by sequencing the entire EXT2 gene., (Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Chiari-like malformation (CM) and syringomyelia (SM) cause a pain syndrome in Cavalier King Charles spaniels (CKCS). Clinical signs are not consistently apparent on neurologic examination, and owner reporting of signs provides vital clinical history. However, owner questionnaires for this disease are not well developed., Objectives: To develop a tool to capture owner-reported clinical signs for use in clinical trials and to compare owner-reported signs with the presence of pain on neurologic examination and SM on magnetic resonance imaging (MRI)., Animals: Fifty client-owned CKCS., Methods: Owners completed a questionnaire and pain/scratch map. Each dog underwent a neurologic examination and craniocervical magnetic resonance imaging (MRI). Questionnaire responses were developed into scores, area of shading for pain/scratch maps was measured, and consistency of responses between these tools was assessed. Owner-reported findings were compared with neurologic examination findings and presence and severity of SM on MRI., Results: Thirty-three dogs were symptomatic and 17 asymptomatic; 30 had SM. The most common sign of pain was crying out when lifted (n = 11). Extent of shaded areas on maps positively correlated with questionnaire scores for pain (r 2  = 0.213, P = 0.006) and scratch (r 2  = 0.104, P = 0.089). Owner-reported findings were not significantly associated with presence or severity of SM or neurologic examination findings. Owner-reported lateralization of signs was significantly associated with SM lateralization (P < 0.0001)., Conclusions: The questionnaire and maps may be useful for clinical trials. Lack of association of owner-reported signs with SM highlights our lack of understanding of the pathophysiology of pain in this disease., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc., on behalf of the American College of Veterinary Internal Medicine.)

Background: Progressive myelomalacia (PMM) is a catastrophic disease associated with acute intervertebral disc extrusion (IVDE). Published data on the clinical characteristics of this disease are limited., Objective: To describe the onset and progression of clinical signs of PMM in a large case cohort., Animals: Fifty-one dogs, 18 with histopathologically confirmed PMM, 33 presumptively diagnosed based on clinical signs and diagnostic imaging., Methods: Retrospective study. Dogs with confirmed IVDE and either a histopathologic diagnosis of PMM or a high clinical suspicion were identified by medical record search. Data on nature and progression of signs were extracted., Results: Twenty-four of 51 dogs were Dachshunds. T12-T13 was the most common site of disc extrusion (12 of 56), and 18 of 55 of mid-to-caudal lumbar discs (between L3 and L6) were affected. Onset of PMM signs ranged from present at first evaluation (17/51) to 5 days after presentation, with 25 of 51 cases developing signs within 48 hours. Progression of signs from onset of PMM to euthanasia or death, excluding 7 cases euthanized at presentation, ranged from 1 to 13 days with 23 being euthanized within 3 days. Nonspecific systemic signs were documented in 30 of 51 dogs., Conclusion and Clinical Importance: The majority of dogs developed PMM within 2 days of presentation and was euthanized within another 3 days. However, onset can be delayed up to 5 days after presentation with progression to euthanasia taking as long as 2 weeks. Mid-to-caudal lumbar discs might be associated with an increased risk of PMM., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Paralysis is a known risk factor for urinary tract infections (UTI), sepsis, and death in paralyzed people, but there are no data available on diagnostic criteria for UTI versus bacteriuria, their frequency, or clinical implications in chronically paralyzed dogs., Hypothesis/objectives: That chronically paralyzed dogs suffer frequent bacteriuria causing reduced duration of survival. We documented the frequency of bacteriuria, associated clinical signs, and survival rate in chronically paralyzed dogs., Animals: Forty-seven client-owned dogs paralyzed with no pelvic limb pain perception for >3 months and at least one urine culture (UC) performed., Methods: Retrospective, observational study. Medical records of dogs meeting inclusion criteria were reviewed for results of UC, urinalysis, and clinical signs. Outcome was compared between dogs with and without bacteriuria., Results: Thirty-five of 47 dogs had at least 1 positive UC, and 13 had recurrent bacteriuria. Rectal temperature and urinalysis results were extracted from records. Fever was present at time of UC in 5 of 68 observations, 2 with and 3 without bacteriuria. Pyuria was significantly associated with positive cultures (P < 0.001), cloudiness was not (P = 0.076). Survival data in 35 dogs (8 dead) showed no association between bacteriuria and survival (P = 0.69)., Conclusions and Clinical Importance: Bacteriuria is common in paralyzed dogs but does not cause fever; diagnostic criteria of UTI are unclear. We did not detect an association of bacteriuria with survival, but this needs further confirmation., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Scottish Terriers have a high incidence of juvenile onset hereditary ataxia primarily affecting the Purkinje neuron of the cerebellar cortex and causing slowly progressive cerebellar dysfunction., Objective: To identify chromosomal regions associated with hereditary ataxia in Scottish Terriers., Animals: One hundred and fifty-three Scottish Terriers were recruited through the Scottish Terrier Club of America., Materials and Methods: Prospective study. Dogs were classified as affected if they had slowly progressive cerebellar signs. When possible, magnetic resonance imaging and histopathological evaluation of the brain were completed as diagnostic aids. To identify genomic regions connected with the disease, genome-wide mapping was performed using both linkage- and association-based approaches. Pedigree evaluation and homozygosity mapping were also performed to examine mode of inheritance and to investigate the region of interest, respectively., Results: Linkage and genome-wide association studies in a cohort of Scottish Terriers both identified a region on CFA X strongly associated with the disease trait. Homozygosity mapping revealed a 4 Mb region of interest. Pedigree evaluation failed to identify the possible mode of inheritance due to the lack of complete litter information., Conclusion and Clinical Importance: This finding suggests that further genetic investigation of the potential region of interest on CFA X should be considered in order to identify the causal mutation as well as develop a genetic test to eliminate the disease from this breed., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Outcome of acute experimental spinal cord injury is strongly associated with tissue perfusion and oxygenation. Cardiopulmonary depression could affect outcome in dogs undergoing general anesthesia for surgical treatment of thoracolumbar intervertebral disk extrusion (IVDE)., Hypothesis/objectives: To evaluate the effects of general anesthesia on functional outcome in dogs undergoing surgery to treat thoracolumbar IVDE., Animals: Eighty-four client-owned dogs with acute thoracolumbar IVDE treated by decompressive hemilaminectomy., Methods: Exploratory, retrospective observational study. Medical records were reviewed for clinical presentation and anesthetic monitoring variables, including duration of anesthesia and surgery, hypotension, bradycardia, temperature, and respiratory parameters. Multivariable regression tree analysis was performed to explore associations between anesthetic variables and functional outcome scores after 6 weeks, as well as return to ambulatory status., Results: Episodes of bradycardia (69%) and hypotension (57%) were frequent. Across all outcome measures, regression tree analysis highlighted functional grade at presentation as the primary determining factor, and among pain perception negative dogs, there was a possible association between increased duration of surgery and poorer outcome. In dogs with intact pain perception, duration of bradycardia, mean body temperature, and mean end-tidal carbon dioxide were highlighted., Conclusions and Clinical Importance: Exploratory statistical methods can facilitate hypothesis-generating studies to inform prospective investigations in veterinary medicine. Although the mechanism is uncertain, increased duration of surgery might be associated with poorer outcome in pain perception negative dogs with thoracolumbar IVDE., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Dogs with spinal cord injury are at increased risk of developing bacteriuria due to increased residual urine volume. Cranberry extract inhibits binding of E. coli to uroepithelial cells, potentially reducing risk of bacteriuria., Hypothesis: Cranberry extract reduces risk of bacteriuria in dogs after acute TL-IVDH., Animals: Client-owned dogs with acute onset TL-IVDH causing nonambulatory status., Methods: Randomized, placebo-controlled, blinded, prospective clinical trial. Dogs with acute TL-IVDH were recruited 48 hours postoperatively and randomized to receive cranberry extract or placebo in a masked fashion. Urine cultures and neurological examinations were performed 2, 4, and 6 weeks postoperatively. The number of dogs with bacteriuria (all bacterial species) and bacteriuria (E. coli) were primary and secondary outcome measures and were evaluated using chi-squared test. Urine antiadhesion activity (AAA) was measured in a subset (N = 47) and examined in a secondary analysis evaluating additional risk factors for bacteriuria., Results: Bacteriuria was detected 17 times in 94 dogs (6 placebo, 11 cranberry, P = .12). There were 7 E. coli. positive cultures (1 placebo, 6 cranberry, P = .09). Dogs in both groups had positive urine AAA (14/21: placebo, 16/26: cranberry), and dogs with urine AAA had significantly fewer E. coli positive cultures (n = 1) than dogs without it (n = 4) (P = .047)., Conclusions and Clinical Importance: This clinical trial did not show a benefit of oral cranberry extract but had low power. Cranberry extract supplementation did not impact urine AAA, but a possible association between urine AAA and lower risk of E. coli bacteriuria was identified. Other doses could be investigated., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Quantification of brain herniation on MRI and its immediate clinical implications are poorly described., Objectives: Define the normal position of caudal fossa structures on brain MRIs in dogs and cats utilizing morphometry, compare this to dogs and cats with caudal transtentorial herniation (CTH), foramen magnum herniation (FMH) or both identified on MRI, and investigate associations between herniation severity, clinical signs, and 24-hour outcome., Animals: Ninety-two controls (66 dogs, 26 cats), 119 cases with herniation (88 dogs, 31 cats)., Methods: Retrospective case series. The MRI database was searched for controls with normal brain anatomy and cases with brain herniation. Morphometry in controls established TTX (transtentorial to rostroventral cerebellum) to quantify CTH and FMX (caudoventral cerebellum to foramen magnum) to quantify FMH. Measurements were compared between cases and controls. Correlations with specific clinical variables and outcome were investigated., Results: Measurements in medium/large control dogs versus small dog and cat controls were significantly different (P < .001, TTX: -0.46, -0.305, -0.3, FMX: 0.695, 0.27, 0.25, respectively). 119/1564 (7.6%) cases that underwent brain imaging had brain herniation. TTX and FMX were significantly different between controls and cases with CTH or FMH (P < .001). 67/89 (75%) cases with supratentorial lesions had no signs directly attributable to herniation. 71/119 (60%) had a normal anesthetic recovery. TTX was significantly associated with 24-hour survival (P < .001)., Conclusions and Clinical Importance: Brain herniation can be quantified on MRI. Clinical signs directly attributable to brain herniation commonly are absent, and more severe CTH based on TTX is associated with a worse short-term outcome., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Monocytes/macrophages are likely key cells in immune modulation in dogs with osteosarcoma (OSA). Increased peripheral monocyte counts are negatively correlated with shorter disease-free intervals in dogs with OSA. Understanding the monocyte/macrophage's modulatory role in dogs with OSA can direct further studies in immunotherapy development for OSA., Hypothesis/objectives: That OSA evades the immune response by down-regulating monocyte chemokine receptor expression and migratory function, and suppresses host immune responses., Animals: Eighteen dogs with OSA that have not received definitive treatment and 14 healthy age-matched controls, Methods: Clinical study-expression of peripheral blood monocyte cell surface receptors, monocyte mRNA expression and cytokine secretion, monocyte chemotaxis, and survival were compared between clinical dogs with OSA and healthy control dogs., Results: Cell surface expression of multiple chemokine receptors is significantly down-regulated in peripheral blood monocytes of dogs with OSA. The percentage expression of CCR2 (median 58%, range 2-94%) and CXCR2 expression (median 54%, range 2-92%) was higher in control dogs compared to dogs with OSA (CCR2 median 29%, range 3-45%, P = 0.0006; CXCR2 median 23%, range 0.2-52%, P = 0.0007). Prostaglandin E2 (PGE2 ) (OSA, median 347.36 pg/mL, range 103.4-1268.5; control, 136.23 pg/mL, range 69.93-542.6, P = .04) and tumor necrosis factor-alpha (TNF-α) (P = .02) levels are increased in OSA monocyte culture supernatants compared to controls. Peripheral blood monocytes of dogs with OSA exhibit decreased chemotactic function when compared to control dogs (OSA, median 1.2 directed to random migration, range 0.8-1.25; control, 1.6, range of 0.9-1.8, P = .018)., Conclusions and Clinical Importance: Dogs with OSA have decreased monocyte chemokine receptor expression and monocyte chemotaxis, potential mechanisms by which OSA might evade the immune response. Reversal of monocyte dysfunction using immunotherapy could improve survival in dogs with OSA., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Limited options are available for the treatment of pain in cats. Monoclonal antibodies (mAbs) that neutralize nerve growth factor (NGF) have demonstrated analgesic capacity in rodent models, people with osteoarthritis, and dogs with degenerative joint disease., Hypothesis/objectives: This study describes the design and characterization of a fully felinized anti-NGF monoclonal antibody. In vitro potency, pharmacokinetics, and the ability of the antibody to treat pain in a self-resolving, acute inflammation model were investigated in cats., Animals: Thirty-eight cats at a research colony at Charles River Laboratories, Ireland., Methods: Felinized anti-NGF mAb, NV-02, was produced using a complementary DNA (cDNA)-based method (PETization). Purified NV-02 was tested for affinity, potency, and immunoreactivity in vitro, then for safety and plasma pharmacokinetic distribution in vivo, and analgesic efficacy in a model of kaolin-induced inflammatory pain., Results: Anti-NGF mAb, NV-02 neutralized NGF with high affinity and potency and did not bind complement. NV-02-administered SC had a plasma half-life of 7-15 days and was well tolerated at dosages up to 28 mg/kg. A dosage of 2 mg/kg NV-02 SC significantly decreased signs of lameness on day 2 (P = .0027), day 3 (P = .016), day 4, (P = .0063), day 5 (P = .0085), day 6 (P = .0014), and day 7 (P = .0034) after induction of inflammation., Conclusions and Clinical Importance: The high affinity, long plasma half-life, safety, and analgesic efficacy of felinized anti-NGF mAb (NV-02) support further investigation of the analgesic potential of this antibody in the cat., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Neutralizing antibodies against nerve growth factor (NGF) are analgesic in rodent models, naturally occurring degenerative joint disease (DJD) pain in dogs, and chronic pain in humans., Objectives: To evaluate the efficacy of a fully felinized anti-NGF antibody (NV-02) for the treatment of DJD pain and mobility impairment in cats., Animals: Thirty-four client-owned cats with DJD-associated pain and mobility impairment., Methods: In a placebo-controlled, pilot, masked clinical study, cats were randomized to a single treatment with NV-02 (0.4 mg/kg SC [n = 11] or 0.8 mg/kg SC [n = 12]) or placebo (saline, SC [n = 11]). Activity was measured objectively. Additionally, owners completed clinical metrology instruments (client-specific outcome measures [CSOM] and feline musculoskeletal pain index [FMPI]) on days 0 (screening), 14 (baseline), 35, 56, and 77. A repeated-measures model was used to evaluate the objective activity data., Results: NV-02 significantly increased objectively measured activity overall (P = .017) and at 2 (P = .035), 3 (P = .007), 4 (P = .006), 5 (P = .007), and 6 (P = .017) weeks after treatment. CSOM scores (P = .035) and pain (P = .024) showed a significant effect of treatment 3 weeks after administration. In the treatment group, 83% of the owners correctly identified the treatment administered compared with 45% of owners in the placebo group (P = .013). No treatment-related adverse effects were identified., Conclusions: These pilot data demonstrate a 6-week duration positive analgesic effect of this fully felinized anti-NGF antibody in cats suffering from DJD-associated pain., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Dysregulated apoptosis is a hallmark of tumorigenesis, and is also involved in resistance to cytotoxic treatment, and might be relevant in lymphoma in dogs., Hypothesis/objectives: That Bcl-2/Bax expression patterns differ between lymphoma immunophenotypes, and that Bcl-2/Bax ratio is correlated with prognosis., Animals: Fifty-five client-owned dogs with multicentric lymphoma and 5 healthy dogs., Methods: Prospective, case-control study. We compared 3 methods (flow cytometry, qRT-PCR, Western blot) for Bcl-2 and Bax quantification in a subset of dogs. The effect of time on Bcl-2/Bax ratios measured by flow cytometry was assessed in lymphoma cell lines. Immunophenotype and Bcl-2/Bax expression by flow cytometry were determined in LN aspirates from all dogs with multicentric lymphoma compared to healthy dogs. Progression-free survival (PFS) was retrospectively evaluated in a group of dogs all receiving similar treatment., Results: Bcl-2/Bax ratios remain consistent for at least 5 days after sample collection. Bcl-2/Bax ratio was higher in dogs with T-cell lymphoma (TCL; median 0.97, range 0.37-1.36) compared to B-cell lymphoma (BCL; median 0.36, range 0.07-1.45) (P < .0001) and normal dogs (median 0.36, range 0.21-0.48) (P = .0006), respectively. Dogs with Bcl-2/Bax ratios higher than the median of the group experienced a median PFS of 101 days and dogs with ratios equal and lower than the median had PFS of 130 days (P = .19)., Conclusions and Clinical Importance: Higher intrinsic resistance to apoptosis following cytotoxic treatment might contribute to the less favorable prognosis associated with multicentric TCL in dogs. Whether Bcl-2/Bax will be helpful to identify canine BCL and TCL with more aggressive and more indolent behavior, respectively, should be evaluated in larger prospective clinical studies., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Intervertebral disc herniation is a common cause of spinal cord injury (SCI) causing paralysis and sensory loss. Little quantitative information is available on the loss and recovery of sensation in dogs with SCI., Objectives: To determine whether quantitative sensory testing (QST) can be used to establish thermal and mechanical sensory thresholds in chrondrodystrophoid dogs and compare thresholds among normal dogs and dogs with different grades of SCI., Animals: Thirty-three client-owned chondrodystrophoid dogs: 15 normal and 18 SCI dogs., Methods: Thermal testing was performed by placing a hot (49°C) and cold (5°C) probe on the dorsal metatarsus and mechanical thresholds were tested using calibrated forceps to apply force to the lateral digit. Stimuli were applied until acknowledged, and response rate, latency, and force applied to response were recorded. Test-retest repeatability was determined by calculating intraclass correlation coefficients. Response rates were compared using logistic regression and thresholds were compared using Kaplan-Meier Survival curves., Results: Testing was feasible with moderate repeatability. Thresholds and response rates were significantly different between normal and SCI dogs for all modalities (P < .001). When dogs were grouped by their clinical grade, each grade was significantly different from normal dogs, and cold stimuli differentiated among all grades., Conclusion and Clinical Importance: Sensory thresholds can be measured reliably in chondrodystrophoid dogs and are altered by SCI. The differences in sensation among neurologic grades indicate that these techniques can be used to further characterize recovery of SCI dogs., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)