Gold Nanostars Obviate Limitations to Laser Interstitial Thermal Therapy (LITT) for the Treatment of Intracranial Tumors.

PURPOSE: Laser interstitial thermal therapy (LITT) is an effective minimally invasive treatment option for intracranial tumors. Our group produced plasmonics-active gold nanostars (GNS) designed to preferentially accumulate within intracranial tumors and amplify the ablative capacity of LITT. EXPERIMENTAL DESIGN: The impact of GNS on LITT coverage capacity was tested in ex vivo models using clinical LITT equipment and agarose gel-based phantoms of control and GNS-infused central "tumors." In vivo accumulation of GNS and amplification of ablation were tested in murine intracranial and extracranial tumor models followed by intravenous GNS injection, PET/CT, two-photon photoluminescence, inductively coupled plasma mass spectrometry (ICP-MS), histopathology, and laser ablation. RESULTS: Monte Carlo simulations demonstrated the potential of GNS to accelerate and specify thermal distributions. In ex vivo cuboid tumor phantoms, the GNS-infused phantom heated 5.5× faster than the control. In a split-cylinder tumor phantom, the GNS-infused border heated 2× faster and the surrounding area was exposed to 30% lower temperatures, with margin conformation observed in a model of irregular GNS distribution. In vivo, GNS preferentially accumulated within intracranial tumors on PET/CT, two-photon photoluminescence, and ICP-MS at 24 and 72 hours and significantly expedited and increased the maximal temperature achieved in laser ablation compared with control. CONCLUSIONS: Our results provide evidence for use of GNS to improve the efficiency and potentially safety of LITT. The in vivo data support selective accumulation within intracranial tumors and amplification of laser ablation, and the GNS-infused phantom experiments demonstrate increased rates of heating, heat contouring to tumor borders, and decreased heating of surrounding regions representing normal structures.

Presumed pituitary apoplexy in 26 dogs: Clinical findings, treatments, and outcomes.

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.

Inter-pathologist agreement on diagnosis, classification and grading of canine glioma.

Histopathological evaluation of tumours is a subjective process, but studies of inter-pathologist agreement are uncommon in veterinary medicine. The Comparative Brain Tumour Consortium (CBTC) recently published diagnostic criteria for canine gliomas. Our objective was to assess the degree of inter-pathologist agreement on intracranial canine gliomas, utilising the CBTC diagnostic criteria in a cohort of eighty-five samples from dogs with an archival diagnosis of intracranial glioma. Five pathologists independently reviewed H&E and immunohistochemistry sections and provided a diagnosis and grade. Percentage agreement and kappa statistics were calculated to measure inter-pathologist agreement between pairs and amongst the entire group. A consensus diagnosis of glioma subtype and grade was achieved for 71/85 (84%) cases. For these cases, percentage agreement on combined diagnosis (subtype and grade), subtype only and grade only were 66%, 80% and 82%, respectively. Kappa statistics for the same were 0.466, 0.542 and 0.516, respectively. Kappa statistics for oligodendroglioma, astrocytoma and undefined glioma were 0.585, 0.566 and 0.280 and were 0.516 for both low-grade and high-grade tumours. Kappa statistics amongst pairs of pathologists for combined diagnosis varied from 0.352 to 0.839. 8 % of archival oligodendrogliomas and 61% of archival astrocytomas were reclassified as another entity after review. Inter-pathologist agreement utilising CBTC guidelines for canine glioma was moderate overall but varied from fair to almost perfect between pairs of pathologists. Agreement was similar for oligodendrogliomas and astrocytomas but lower for undefined gliomas. These results are similar to pathologist agreement in human glioma studies and with other tumour entities in veterinary medicine.

Subaxial cervical articular process subluxation and dislocation: Cervical locked facet injuries in dogs.

OBJECTIVE: To describe neurologic signs, diagnostic imaging findings, potential treatments, and outcomes in dogs with subaxial cervical articular process subluxation and dislocation, or a "locked facet." STUDY DESIGN: Retrospective case series. ANIMALS: Ten client-owned dogs. METHODS: Dogs with a diagnosis of cervical locked facets were identified through medical records and imaging reports searches. Data on presenting signs, diagnostic findings, treatment, and outcome were recorded. RESULTS: All cases were small or toy-breed dogs with preceding trauma. Four dogs were tetraplegic with intact pain perception, five were nonambulatory tetraparetic, and one was ambulatory tetraparetic, with half of the tetraparetic dogs having worse motor function in the thoracic limbs. The only sites affected were C5/6 (n = 6) and C6/7 (n = 4). All dogs had unilateral dorsal displacement of the cranial articular process of the caudal vertebra relative to the caudal articular process of the cranial vertebra at the luxation site. Five dogs were treated surgically, three by external coaptation, one by restriction, and one was euthanized the day after diagnosis. All dogs with outcome data (n = 8) became ambulatory. Nonambulatory dogs returned to ambulation in a median of 4 weeks (IQR 1-12; range 1-28). CONCLUSION: In these dogs, locked facet injuries affected the caudal cervical vertebrae in small breeds and could be identified on imaging through the presence of dorsal displacement of a cranial articular process. Our small cohort had a functional recovery regardless of treatment. CLINICAL SIGNIICANCE: Locked facet injuries should be a differential for small or toy-breed dogs with a cervical myelopathy secondary to trauma.

High-field MRI using standard pulse sequences has moderate to substantial interobserver agreement and good accuracy for differentiation between intracranial extra-axial histiocytic sarcoma and meningioma in dogs.

Intracranial extra-axial histiocytic sarcoma shares common MRI features with meningioma. As histiocytic sarcoma carries a generally worse prognosis than meningioma, the ability to differentiate between these two neoplasms is of clinical value. The aim of this retrospective diagnostic accuracy and observer agreement study was to evaluate the accuracy and reliability of high-field MRI to differentiate between these two tumors, using standard pulse sequences and published MRI features. A total of 51 dogs were included (26 meningiomas and 25 histiocytic sarcomas). Magnetic resonance imaging examinations were independently assessed by three experienced board-certified radiologists, evaluating 18 imaging features. They were asked to assign each case to one of three categories (meningioma, histiocytic sarcoma, and undetermined). Agreement for the MRI diagnosis across all three reviewers was moderate (κ 0.54) while paired interobserver agreement ranged from moderate to substantial (κ 0.58-0.74) with percent agreement ranging between 86.1% and 87.7%. Overall, the probability of correctly diagnosing meningioma in a dog with this tumor ranged between 79.2% and 94.4%, and the probability of correctly diagnosing histiocytic sarcoma in a dog with this tumor ranged between 76.0% and 92.3%. The overall probability to diagnose the correct tumor, irrespective of type, ranged between 79.2% and 89.7%. Histiocytic sarcomas tended to have more extensive edema and more often had combined perilesional and distant meningeal enhancement affecting both pachy- and leptomeninges, while for meningiomas, meningeal enhancement tended to more commonly be perilesional and pachymeningeal. Imaging features that seemed more useful to make a correct diagnosis included "location/type of meningeal enhancement," "osseous changes in the adjacent neurocranium," "cystic changes," and "herniation severity."

Immunohistochemical evaluation of immune cell infiltration in canine gliomas.

Evasion of the immune response is an integral part of the pathogenesis of glioma. In humans, important mechanisms of immune evasion include recruitment of regulatory T cells (Tregs) and polarization of macrophages toward an M2 phenotype. Canine glioma has a robust immune cell infiltrate that has not been extensively characterized. The purpose of this study was to determine the distribution of immune cells infiltrating spontaneous intracranial canine gliomas. Seventy-three formalin-fixed, paraffin-embedded tumor samples were evaluated using immunohistochemistry for CD3, forkhead box 3 (FOXP3), CD20, Iba1, calprotectin (Mac387), CD163, and indoleamine 2,3-dioxygenase (IDO). Immune cell infiltration was present in all tumors. Low-grade and high-grade gliomas significantly differed in the numbers of FoxP3+ cells, Mac387+ cells, and CD163+ cells (P = .006, .01, and .01, respectively). Considering all tumors, there was a significant increase in tumor area fraction of CD163 compared to Mac387 (P < .0001), and this ratio was greater in high-grade tumors than in low-grade tumors (P = .005). These data warrant further exploration into the roles of macrophage repolarization or Treg interference therapy in canine glioma.

Vascular endothelial growth factor concentrations in the cerebrospinal fluid of dogs with neoplastic or inflammatory central nervous system disorders.

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.

Personalized-induced neural stem cell therapy: Generation, transplant, and safety in a large animal model.

In this study, we take an important step toward clinical translation by generating the first canine-induced neural stem cells (iNSCs). We explore key aspects of scale-up, persistence, and safety of personalized iNSC therapy in autologous canine surgery models. iNSCs are a promising new approach to treat aggressive cancers of the brain, including the deadly glioblastoma. Created by direct transdifferentiation of fibroblasts, iNSCs are known to migrate through the brain, track down invasive cancer foci, and deliver anticancer payloads that significantly reduce tumor burden and extend survival of tumor-bearing mice. Here, skin biopsies were collected from canines and converted into the first personalized canine iNSCs engineered to carry TNFα-related apoptosis-inducing ligand (TRAIL) and thymidine kinase (TK), as well as magnetic resonance imaging (MRI) contrast agents for in vivo tracking. Time-lapse analysis showed canine iNSCs efficiently migrate to human tumor cells, and cell viability assays showed both TRAIL and TK monotherapy markedly reduced tumor growth. Using intraoperative navigation and two delivery methods to closely mimic human therapy, canines received autologous iNSCs either within postsurgical cavities in a biocompatible matrix or via a catheter placed in the lateral ventricle. Both strategies were well tolerated, and serial MRI showed hypointense regions at the implant sites that remained stable through 86 days postimplant. Serial fluid sample testing following iNSC delivery showed the bimodal personalized therapy was well tolerated, with no iNSC-induced abnormal tissue pathology. Overall, this study lays an important foundation as this promising personalized cell therapy advances toward human patient testing.

Use of Top Hat Audience Response Software in a Third-Year Veterinary Medicine and Surgery Course.

Audience response devices are useful tools that can improve student engagement and learning during instructional sessions. The purpose of this article is to describe our experience with a new cloud-based application known as Top Hat, which includes audience response tools in its application suite. The software was used in a multi-specialty, multi-instructor medicine and surgery course in the third year of a veterinary curriculum. In addition to standard multiple-choice and short-answer questions, Top Hat has several unique question types and methods of displaying the responses given. These include displaying free-text responses in a word cloud format and a "click-on-target" question type that allows students to indicate their response by clicking on a location within an image. Responses for this latter question type are displayed in a heat map format. A discussion tool is also available, which allows students to respond, read other students' responses in real time, and then reply again if warranted. This feature also supports drawing-based responses. The variety of question types was very useful in keeping students engaged during teaching sessions, giving this application several advantages over systems that are limited to multiple-choice questions only. In addition, the application allowed rapid identification of areas of student knowledge and misunderstandings, which facilitated the direction of further discussion and clarification of important learning issues.

Accuracy and safety of three-dimensionally printed animal-specific drill guides for thoracolumbar vertebral column instrumentation in dogs: Bilateral and unilateral designs.

OBJECTIVE: To evaluate the safety and accuracy of a unilateral three-dimensionally printed animal-specific drill guide (3DASDG) design for unilateral stabilization in the thoracolumbar vertebral column of dogs compared to a bilateral design. STUDY DESIGN: Cadaveric study. SAMPLE POPULATION: Fifty-two corridors in one canine cadaver. METHODS: Two 3DASDG designs with 2 drilling tubes each were created from T8 to L7 vertebrae. Fifty-two corridors were drilled on the right and the left sides by using unilateral and bilateral designs, respectively. Planned and postoperative trajectories (entry point, exit point, angle) were compared to establish the accuracy. Statistical analysis was used for accuracy comparison between designs. Safety was evaluated by using Zdichavsky classification. RESULTS: Unilateral and bilateral drill guide designs were not different for entry point and angle deviations; however, they were different for the exit point deviations. Two corridors breached outside the vertebra. For all guides, mean entry and exit point deviations were less than 1 and 2 mm, respectively. The maximum entry or exit point deviation in both groups was 4.7 mm. The mean angle deviation was <3.5°, and the maximum angle deviation was 9.3°. CONCLUSION: No difference was detected in accuracy of entry points and angle deviations between drill guide designs tested in normal vertebrae. The technique was classified as highly safe. CLINICAL SIGNIFICANCE: A unilateral drill guide design may be a safe alternative to bilateral guides for unilateral stabilization of the thoracolumbar vertebral column in dogs.

Accuracy of three-dimensionally printed animal-specific drill guides for implant placement in canine thoracic vertebrae: A cadaveric study.

OBJECTIVE: To assess the accuracy of three-dimensionally (3-D) printed drill guides in constraining the trajectory of drill tracts for implants in canine thoracic vertebrae. STUDY DESIGN: Experimental ex vivo study. SAMPLE POPULATION: Five canine thoracic vertebral column specimens. METHODS: Guides to constrain drill trajectories were designed on the basis of computed tomographic (CT) imaging of six thoracic vertebrae (T8-T13) and were 3-D printed. The guides were used to create drill tracts in these vertebrae by both an experienced and a novice surgeon, and CT imaging was repeated. The entry point and angulation of actual and planned drill tracts were compared for both surgeons. Unintended cortical violations were also assessed by using a modified Zdichavsky classification. RESULTS: Fifty-eight drill tracts were created in 30 vertebrae. Mean entry point deviation was 1.4 mm (range, 0.4-3.4), and mean angular deviation was 5.1° (range, 1.5°-10.8°). There were no differences between surgeons in entry point deviation (P = .07) or angular deviation (P = .22). There were no unintended cortical bone violations, and all drill tracts were classified as modified Zdichavsky grade I. CONCLUSION: The 3-D printed guides used in the current study yielded drill tracts with small linear and angular errors from intended paths and 100% accuracy for placement within vertebral pedicles and bodies. This technique was conveniently used by both an experienced and a novice surgeon. CLINICAL SIGNIFICANCE: This technique might be immediately applicable to clinical cases requiring thoracic vertebral stabilization and may allow safe and accurate implant placement for surgeons with varying experience levels.

Cerebrospinal fluid lactate concentrations in dogs with seizure disorders.

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.

Association between anesthesia duration and outcome in dogs with surgically treated acute severe spinal cord injury caused by thoracolumbar intervertebral disk herniation.

BACKGROUND: Retrospective research recently identified a possible relationship between duration of surgery and outcome in severely affected dogs treated surgically for acute thoracolumbar intervertebral disk herniation (TL-IVDH). HYPOTHESIS: That increased duration of surgery is associated with poorer outcome in dogs with absent pain perception treated surgically for TL-IVDH. ANIMALS: Two hundred ninety-seven paraplegic dogs with absent pain perception surgically treated for acute TL-IVDH. METHODS: Retrospective cohort study. Medical records of 5 institutions were reviewed. Inclusion criteria were paraplegia with absence of pain perception, surgical treatment of TL-IVDH, and 1-year postoperative outcome (ambulatory: yes or no). Canine data, outcome, and surgery and total anesthesia duration were retrieved. RESULTS: In this study, 183/297 (61.6%) dogs were ambulatory within 1 year, 114 (38.4%) dogs failed to recover, including 74 dogs (24.9%) euthanized because of progressive myelomalacia. Median anesthesia duration in dogs that regained ambulation within 1 year of surgery (4.0 hours, interquartile range [IQR] 3.2-5.1) was significantly shorter than those that did not (4.5 hours, IQR 3.7-5.6, P = .01). Multivariable logistic regression demonstrated a significant negative association between both duration of surgery and total anesthesia time and ambulation at 1 year when controlling for body weight and number of disk spaces operated on. CONCLUSIONS AND CLINICAL IMPORTANCE: Findings support a negative association between increased duration of anesthesia and outcome in this group of dogs. However, the retrospective nature of the data does not imply a causal relationship.

Risk factors associated with progressive myelomalacia in dogs with complete sensorimotor loss following intervertebral disc extrusion: a retrospective case-control study.

BACKGROUND: Progressive myelomalacia (PMM) is a usually fatal complication of acute intervertebral disc extrusion (IVDE) in dogs but its risk factors are poorly understood. The objective of this retrospective case-control study was to identify risk factors for PMM by comparing dogs with complete sensorimotor loss following IVDE that did and did not develop the disease after surgery. We also investigated whether any risk factors for PMM influenced return of ambulation. Medical records of client-owned dogs with paraplegia and loss of pain perception that underwent surgery for IVDE from 1998 to 2016, were reviewed. Dogs were categorized as PMM yes or no based on clinical progression or histopathology. Walking outcome at 6 months was established. Signalment, onset and duration of signs (categorized), steroids, non-steroidal anti-inflammatory drugs (yes or no), site of IVDE (lumbar intumescence or thoracolumbar) and longitudinal extent of IVDE were retrieved and their associations with PMM and walking outcome were examined using logistic regression. RESULTS: One hundred and ninety seven dogs were included, 45 with and 152 without PMM. A 6-month-outcome was available in 178 dogs (all 45 PMM dogs and 133 control dogs); 86 recovered walking (all in the control group). Disc extrusions at the lumbar intumescence were associated with PMM (p = 0.01, OR: 3.02, CI: 1.3-7.2). Surgery performed more than 12 h after loss of ambulation was associated with PMM (OR = 3.4; CI = 1.1-10.5, p = 0.03 for 12-24 h and OR = 4.6; CI = 1.3-16.6, p = 0.02 for the > 24 h categories when compared with the ≤12 h category). Treatment with corticosteroids was negatively associated with PMM (OR: 3.1; CI: 1.3-7.6, p = 0.01). The only variable to affect walking outcome was longitudinal extent of IVDE (OR = 2.6; CI = 1.3-5.3, p = 0.006). CONCLUSION: Dogs with lumbar intumescence IVDE are at increased risk of PMM. Timing of surgery and corticosteroid use warrant further investigations. PMM and recovery of walking are influenced by different factors.

Presence of cerebrospinal fluid antibodies associated with autoimmune encephalitis of humans in dogs with neurologic disease.

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.

Time course and prognostic value of serum GFAP, pNFH, and S100ß concentrations in dogs with complete spinal cord injury because of intervertebral disc extrusion.

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 S100ß 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 S100ß 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 S100ß 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.

Optic neuritis in dogs: 96 cases (1983-2016).

OBJECTIVE: To characterize ocular and neurologic findings, causes, and treatment outcomes of dogs with optic neuritis. PROCEDURE: Medical records from dogs with a diagnosis of optic neuritis at North Carolina State University, College of Veterinary Medicine, Veterinary Hospital between 1983 and 2016 were reviewed. RESULTS: Ninety-six cases (20 unilateral, 76 bilateral), comprised of 38 males and 58 females with a mean age of 6.1 ± 3.0 years (range 0.5-13), were identified. Seventy-four cases were presented for vision loss, and 42 had other concurrent neurologic abnormalities. Funduscopic findings included optic nerve head elevation (n = 92), peripapillary retinal edema or separation (n = 37), retinal hemorrhage or dilation of retinal vasculature (n = 23), and multiple inflammatory foci in the peripapillary region (n = 13). Retrobulbar optic neuritis was diagnosed in four cases. The final diagnoses included the following: multifocal meningoencephalitis of unknown etiology (MUE, n = 35), isolated optic neuritis (I-ON, n = 42), neoplasia (n = 10), microbial infection (n = 6), orbital inflammation (n = 2), and suspected ivermectin toxicosis (n = 1). Dogs with I-ON were more commonly male, and medium-to-large breed, when compared to dogs with MUE. Follow-up was available in 72 cases, 50 of which remained blind, 10 had partial visual improvement, and 12 were assessed as having normal vision in the affected eye(s). CONCLUSION: Optic neuritis was most commonly associated with multifocal MUE or was isolated as the sole neurologic finding, with a similar incidence between the two groups. Findings suggest that a clinical syndrome of isolated optic neuritis, distinct from multifocal MUE, occurs in dogs.

Perianesthetic morbidity and mortality in dogs undergoing cervical and thoracolumbar spinal surgery.

OBJECTIVE: To evaluate and compare perioperative morbidity and mortality in dogs undergoing cervical and thoracolumbar spinal surgery. STUDY DESIGN: Prospective case series. ANIMALS: 157 dogs undergoing cervical or thoracolumbar spinal surgery. METHODS: Data were collected sequentially on canine cases presented from the Neurology Section of the North Carolina State University Veterinary Teaching Hospital for anesthesia and surgery for cervical spinal cord disease. Simultaneously, data were collected on all thoracolumbar spinal surgery cases during the same time period. Data included signalment, drugs administered, surgical approach, disease process, cardiac arrhythmias during anesthesia, and outcome. RESULTS: Data were collected from 164 surgical events in 157 dogs. There were 52 cervical approaches; four dorsal and 48 ventral. All thoracolumbar surgeries were approached dorsolaterally. Four dogs 4/52 (7.6%) undergoing a cervical approach did not survive to discharge. Two dogs (2/8; 25%) underwent atlanto-axial (AA) stabilization and suffered cardiovascular arrest and two dogs (2/38; 5.2%) undergoing cervical ventral slot procedures were euthanized following anesthesia and surgery due to signs of aspiration pneumonia. All dogs undergoing thoracolumbar surgery survived until discharge (112/112). Mortality in dogs undergoing cervical spinal surgery was greater compared with dogs undergoing thoracolumbar spinal surgery (p = 0.009), however, in dogs undergoing decompressive disc surgery, intraoperative death rates were not different between dogs undergoing a cervical compared with thoracolumbar approaches (p = 0.32) nor was there a significant difference in overall mortality (p = 0.07). CONCLUSION AND CLINICAL RELEVANCE: Overall, dogs undergoing cervical spinal surgery were less likely to survive until discharge compared with dogs undergoing thoracolumbar spinal surgery. Mortality in dogs undergoing cervical intervertebral disc decompression surgery was no different than for dogs undergoing thoracolumbar intervertebral disc decompression surgery. However, dogs undergoing cervical intervertebral disc decompression surgery should be considered at risk for aspiration pneumonia.

Evaluation of matrix metalloproteinase-2 and -9 in the cerebrospinal fluid of dogs with intracranial tumors.

OBJECTIVE: To identify matrix metalloproteinase (MMP)-2 and -9 in CSF from dogs with intracranial tumors. SAMPLE: CSF from 55 dogs with intracranial tumors and 37 control dogs. PROCEDURES: Latent and active MMP-2 and -9 were identified by use of gelatin zymography. The presence of MMPs in the CSF of dogs with intracranial tumors was compared with control dogs that were clinically normal and with dogs that had idiopathic or cryptogenic epilepsy or peripheral vestibular disease. Relationships between MMP-9 and CSF cell counts and protein were also investigated. RESULTS: Latent MMP-2 was found in CSF samples from all dogs, although active MMP-2 was not detected in any sample. Latent MMP-9 was detected in a subset of dogs with histologically documented intracranial tumors, including meningiomas (2/10), gliomas (3/10), pituitary tumors (1/2), choroid plexus tumors (5/6), and lymphoma (4/4), but was not detected in any control samples. Dogs with tumors were significantly more likely than those without to have detectable MMP-9 in the CSF, and the presence of MMP-9 was associated with higher CSF nucleated cell counts and protein concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Latent MMP-9 was detected in most dogs with choroid plexus tumors or lymphoma but in a smaller percentage of dogs with meningiomas, gliomas, or pituitary tumors. Detection of MMP in CSF may prove useful as a marker of intracranial neoplasia or possibly to monitor response of tumors to therapeutic intervention.

Isolation and characterization of neural progenitor cells from adult canine brains.

OBJECTIVE: To isolate and characterize neural stem and progenitor cell populations in the brain of adult dogs. ANIMALS: 7 healthy adult dogs. PROCEDURES: Dogs (age, 10 to 60 months) were euthanized for reasons unrelated to the study. The subventricular zone (SVZ) adjacent to the lateral ventricles and subgranular zone (SGZ) of the hippocampus were isolated and used to generate single cell suspensions for nonadherent culture. The resulting primary neurospheres were serially passaged to assess self-renewal capacity. Neurospheres were differentiated by the withdrawal of growth factors and the addition of serum. Differentiated and undifferentiated neurospheres were analyzed via reverse transcriptase PCR assay or immunocytochemical staining for markers of pluripotency and neural lineage. RESULTS: Neurospheres were generated from the SVZ and SGZ in all dogs. The SVZ generated more primary neurospheres than did the SGZ. Serial passage was successful, although few neurospheres could be generated after the fifth passage. Undifferentiated neurospheres were positive for SOX2, nestin, and glial fibrillary acidic protein (GFAP) and negative for OCT4 and NANOG. After differentiation, GFAP, neuronal class III ß-tubulin, and 2', 3'-cyclic nucleotide 3'-phosphodiesterase-positive progeny were noted migrating out of the neurospheres. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested the persistence of SOX2-positive, nestin-positive, GFAP-positive, OCT4-negative, and NANOG-negative neural progenitor cells in the SVZ and SGZ regions of mature canine brains, which are capable of producing multiple cell lineages. This study may serve as a basis for future studies investigating the role of these cells in various disease processes, such as neoplasia, or for regenerative purposes.