Browsing by Author "Pancotto, Theresa E."

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    Canine Butterfly Glioblastomas: a Neuroradiological Review
    Rossmeisl, John H. Jr.; Clapp, Kemba; Pancotto, Theresa E.; Emch, Samantha; Robertson, John L.; Debinski, Waldemar (Frontiers, 2016-05-19)
    In humans, high-grade gliomas may infiltrate across the corpus callosum resulting in bihemispheric lesions that may have symmetrical, winged-like appearances. This particular tumor manifestation has been coined a “butterfly” glioma (BG). While canine and human gliomas share many neuroradiological and pathological features, the BG morphology has not been previously reported in dogs. Here, we describe the magnetic resonance imaging (MRI) characteristics of BG in three dogs and review the potential differential diagnoses based on neuroimaging findings. All dogs presented for generalized seizures and interictal neurological deficits referable to multifocal or diffuse forebrain disease. MRI examinations revealed asymmetrical (2/3) or symmetrical (1/3), bihemispheric intra-axial mass lesions that predominantly affected the frontoparietal lobes that were associated with extensive perilesional edema, and involvement of the corpus callosum. The masses displayed heterogeneous T1, T2, and fluid-attenuated inversion recovery signal intensities, variable contrast enhancement (2/3), and mass effect. All tumors demonstrated classical histopathological features of glioblastoma multiforme (GBM), including glial cell pseudopalisading, serpentine necrosis, microvascular proliferation as well as invasion of the corpus callosum by neoplastic astrocytes. Although rare, GBM should be considered a differential diagnosis in dogs with an MRI evidence of asymmetric or symmetric bilateral, intra-axial cerebral mass lesions with signal characteristics compatible with glioma.
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    A case of stiff dog syndrome associated with anti-glutamic acid decarboxylase antibodies
    Pancotto, Theresa E.; Rossmeisl, John H. Jr. (2017-05-10)
    Background The stiff person syndrome (SPS) is a rare and debilitating autoimmune disorder with an unknown pathogenesis and variable clinical presentation that can present a diagnostic challenge. Although entities that clinically mimic stiff-person spectrum disorders (SPSD) have manifested in horses, they have not been reported in dogs. Case presentation We describe a 2-year-old beagle dog presented for progressive attacks of muscular rigidity and lordosis with superimposed spasms of the appendicular muscles triggered by tactile stimulation which resulted in marked gait impairment. Resting electromyography revealed continuous motor unit activity in the axial musculature. Compared to age-matched healthy beagle dogs, this patient had elevated glutamic acid decarboxylase antibody concentrations in serum and cerebrospinal fluid. Conclusions This dog presented with phenotypic, electrodiagnostic, and immunologic criterion consistent with an SPSD, including elevated anti-GAD antibody titers, which we have termed the “stiff dog syndrome (SDS)”. Durable clinical improvement was achieved with symptomatic and immunosuppressive treatments including baclofen, gabapentin, prednisone, and intravenous immunoglobulin.
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    Computed Tomography and Magnetic Resonance Imaging Are Equivalent in Mensuration and Similarly Inaccurate in Grade and Type Predictability of Canine Intracranial Gliomas
    Stadler, Krystina L.; Ruth, Jeffrey D.; Pancotto, Theresa E.; Werre, Stephen R.; Rossmeisl, John H. Jr. (Frontiers, 2017-09-25)
    While magnetic resonance imaging (MRI) is the gold-standard imaging modality for diagnosis of intracranial neoplasia, computed tomography (CT) remains commonly used for diagnosis and therapeutic planning in veterinary medicine. Despite the routine use of both imaging modalities, comparison of CT and MRI has not been described in the canine patient. A retrospective study was performed to evaluate CT and MRI studies of 15 dogs with histologically confirmed glioma. Multiple lesion measurements were obtained, including two-dimensional and volumetric dimensions in pre-contrast and post-contrast images. Similar measurement techniques were compared between CT and MRI. The glioma type (astrocytoma or oligodendroglioma) and grade (high or low) were predicted on CT and MRI independently. With the exception of the comparison between CT pre-contrast volume to T2-weighted MRI volume, no other statistical differences between CT and MRI measurements were identified. Overall accuracy for tumor grade (high or low) was 46.7 and 53.3% for CT and MRI, respectively. For predicted tumor type, accuracy of CT was 53.3% and MRI and MRI 60%. Based on the results of this study, both CT and MRI contrast measurement techniques are considered equivalent options for lesion mensuration. Given the low-to-moderate predictability of CT and MRI in glioma diagnosis, histopathology remains necessary for accurate diagnosis of canine brain tumors.
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    Development and Evaluation of a Caregiver Reported Quality of Life Assessment Instrument in Dogs With Intracranial Disease
    Weiske, Rebecca; Sroufe, Maureen; Quigley, Mindy; Pancotto, Theresa E.; Werre, Stephen R.; Rossmeisl, John H. Jr. (2020-08-18)
    In veterinary medicine, quality of life (QOL) assessment instruments, which are important components of the holistic evaluation of treatment success, have largely not included organ-specific concerns that may be broadly relevant to caregivers of dogs with intracranial disease. The objective of this study was to identify core questionnaire items and domains that contribute to health-related QOL (HRQOL) in dogs with intracranial disease. A questionnaire was developed that contained 39 QOL-related items encompassing physical, social/companionship, and brain-specific domains associated with the treatment of dogs with intracranial disease, and administered to caregivers of 56 dogs diagnosed with genetic, inflammatory, neoplastic, traumatic, and vascular brain diseases, 52 healthy dogs, and 20 dogs with non-neurological illnesses. Clinician derived functional measures of each dog's health status including chronic pain, Karnofsky performance, and modified Glasgow coma scale scores were also recorded. Principal component analysis refined the final questionnaire, termed the CanBrainQOL-24, to 24-items within the three domains with a minimum Cronbach's alpha of 0.7, indicative of good internal consistency. The CanBrainQOL-24 discriminated between healthy and diseased dogs. Physical and brain-specific domains were significantly different between dogs with intracranial and non-neurological diseases. Significant correlations were observed between owner reported visual analog scores and CanBrainQOL-24 scores, as well between clinician derived functional status measures and owner reported QOL. The CanBrainQOL-24 contains core questions relevant to caregiver assessment of HRQOL in dogs with a variety of intracranial diseases, and provides information that is complementary to clinician derived functional outcome measures.
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    Evaluation of cerebrospinal fluid biomarkers of endothelial damage and basement membrane degradation as indirect indicators of blood-brain barrier dysfunction in chronic canine hypothyroidism
    Pancotto, Theresa E. (Virginia Tech, 2011-02-24)
    A variety of neurologic illnesses including peripheral and cranial neuropathies, central vestibular disease, seizures and coma have been associated with hypothyroidism in dogs. Repeated studies have shown that there is loss of blood brain barrier (BBB) integrity in these animals. Current research has also shown the development cerebrospinal fluid abnormalities in neurologically normal hypothyroid dogs; a finding that is related to BBB degradation. This derangement may be secondary to atherosclerosis and vascular accidents. One possible mediator of vasospasm and ischemic brain injury is endothelin-1 (ET-1). Another group of mediators of vascular dysfunction that has been found in CSF of dogs with various other CNS diseases is matrix metalloproteinases (MMP). The purpose of this study was to assay molecular markers that may contribute to disruption in the blood brain barrier in chronically hypothyroid canines. We hypothesized that BBB disruption in hypothyroidism is mediated by ET-1 and MMPs, as evidenced by increased concentrations of these proteins in CSF compared to controls. Cerebrospinal fluid (CSF) previously collected from 9 control and 9 experimentally induced hypothyroid dogs was used. Administration of I-131 was used to create the experimental model. CSF from time points 0, 6, 12, and 18 months post-induction were evaluated using an ELISA kit for endothelin-1. CSF from each time point was also evaluated using gelatinase zymography to detect MMP-2,9, and 14. The endothelin assay was able to detect ET-1 in CSF as determined by a spike and recovery method. However, ET-1 was undetectable in CSF of control and hypothyroid dogs at all time points. Constitutively expressed MMP-2 was detectable in all dogs at all time points. No other MMPs were detectable in CSF. ET-1 and gelatinase MMP,-9, and -14 are not primary mediators of BBB damage in chronically hypothyroid dogs. They could be involved secondarily and may be better evaluated with different assays or in temporal association with the development of clinical signs of neurologic dysfunction. Additional research is needed to confirm this finding and to evaluate biomarkers of non-vascular components of the BBB.
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    High-Frequency Irreversible Electroporation for Intracranial Meningioma: A Feasibility Study in a Spontaneous Canine Tumor Model
    Latouche, Eduardo L.; Arena, Christopher B.; Ivey, Jill W.; Garcia, Paulo A.; Pancotto, Theresa E.; Pavlisko, Noah; Verbridge, Scott S.; Davalos, Rafael V.; Rossmeisl, John H. Jr. (Sage, 2018)
    High-frequency irreversible electroporation is a nonthermal method of tissue ablation that uses bursts of 0.5- to 2.0-microsecond bipolar electric pulses to permeabilize cell membranes and induce cell death. High-frequency irreversible electroporation has potential advantages for use in neurosurgery, including the ability to deliver pulses without inducing muscle contraction, inherent selectivity against malignant cells, and the capability of simultaneously opening the blood–brain barrier surrounding regions of ablation. Our objective was to determine whether high-frequency irreversible electroporation pulses capable of tumor ablation could be delivered to dogs with intracranial meningiomas. Three dogs with intracranial meningiomas were treated. Patient-specific treatment plans were generated using magnetic resonance imaging-based tissue segmentation, volumetric meshing, and finite element modeling. Following tumor biopsy, high-frequency irreversible electroporation pulses were stereotactically delivered in situ followed by tumor resection and morphologic and volumetric assessments of ablations. Clinical evaluations of treatment included pre- and posttreatment clinical, laboratory, and magnetic resonance imaging examinations and adverse event monitoring for 2 weeks posttreatment. High-frequency irreversible electroporation pulses were administered successfully in all patients. No adverse events directly attributable to high-frequency irreversible electroporation were observed. Individual ablations resulted in volumes of tumor necrosis ranging from 0.25 to 1.29 cm3. In one dog, nonuniform ablations were observed, with viable tumor cells remaining around foci of intratumoral mineralization. In conclusion, high-frequency irreversible electroporation pulses can be delivered to brain tumors, including areas adjacent to critical vasculature, and are capable of producing clinically relevant volumes of tumor ablation. Mineralization may complicate achievement of complete tumor ablation.
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    Magnetization transfer and diffusion tensor imaging in dogs with intervertebral disk herniation
    Shinn, Richard L.; Pancotto, Theresa E.; Stadler, Krystina L.; Werre, Stephen R.; Rossmeisl, John H. Jr. (Wiley, 2020-10-02)
    Background: Quantitative magnetic resonance imaging (QMRI) techniques of magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) provide microstructural information about the spinal cord. Objective: Compare neurologic grades using the modified Frankel scale with MTR and DTI measurements in dogs with thoracolumbar intervertebral disk herniation (IVDH). Animals: Fifty-one dogs with thoracolumbar IVDH. Methods: Prospective cohort study. Quantitative MRI measurements of the spinal cord were obtained at the region of compression. A linear regression generalized estimating equations model was used to compare QMRI measurements between different neurological grades after adjusting for age, weight, duration of clinical signs, and lesion location. Results: Grade 5 (.79 × 10−3 mm2/s [median],.43−.91 [range]) and axial (1.47 × 10−3 mm2/s,.58−1.8) diffusivity were lower compared to grades 2 (1.003,.68−1.36; P =.02 and 1.81 × 10−3 mm2/s, 1.36−2.12; P <.001, respectively) and 3 (1.07 × 10−3 mm2/s,.77−1.5; P =.04 and 1.92 × 10−3 mm2/s, 1.83−2.37; P <.001, respectively). Compared to dogs with acute myelopathy, chronic myelopathy was associated with higher mean (1.02 × 10−3 mm2/s,.77−1.36 vs.83 × 10−3 mm2/s,.64−1.5; P =.03) and radial diffusivity (.75 × 10−3 mm2/s,.38−1.04 vs.44 × 10−3 mm2/s,.22−1.01; P =.008) and lower MTR (46.76, 31.8−56.43 vs. 54.4, 45.2−62.27; P =.004) and fractional anisotropy (.58,.4−0.75 vs.7,.46−.85; P =.02). Fractional anisotropy was lower in dogs with a T2-weighted intramedullary hyperintensity compared to those without (.7,.45−.85 vs.54,.4−.8; P =.01). Conclusion and Clinical Relevance: Mean diffusivity and AD could serve as surrogates of severity of spinal cord injury and are complementary to the clinical exam in dogs with thoracolumbar IVDH.
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    Non-Thermal Irreversible Electroporation (N-TIRE) and Adjuvant Fractionated Radiotherapeutic Multimodal Therapy for Intracranial Malignant Glioma in a Canine Patient
    Garcia, Paulo A.; Pancotto, Theresa E.; Rossmeisl, John H. Jr.; Henao-Guerrero, Natalia; Gustafson, N. R.; Daniel, Gregory B.; Robertson, John L.; Ellis, Thomas L.; Davalos, Rafael V. (Adenine Press, 2011-02-01)
    Non-thermal irreversible electroporation (N-TIRE) has shown promise as an ablative therapy for a variety of soft-tissue neoplasms. Here we describe the therapeutic planning aspects and first clinical application of N-TIRE for the treatment of an inoperable, spontaneous malignant intracranial glioma in a canine patient. The N-TIRE ablation was performed safely, effectively reduced the tumor volume and associated intracranial hypertension, and provided sufficient improvement in neurological function of the patient to safely undergo adjunctive fractionated radiotherapy (RT) according to current standards of care. Complete remission was achieved based on serial magnetic resonance imaging examinations of the brain, although progressive radiation encephalopathy resulted in the death of the dog 149 days after N-TIRE therapy. The length of survival of this patient was comparable to dogs with intracranial tumors treated via standard excisional surgery and adjunctive fractionated external beam RT. Our results illustrate the potential benefits of N-TIRE for in vivo ablation of undesirable brain tissue, especially when traditional methods of cytoreductive surgery are not possible or ideal, and highlight the potential radiosensitizing effects of N-TIRE on the brain.
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    Perineural Injection for Treatment of Root-Signature Signs Associated with Lateralized Disk Material in Five Dogs (2009-2013)
    Giambuzzi, S.; Pancotto, Theresa E.; Ruth, J. (2016)
    Intervertebral disk disease (IVDD) is common in dogs; cervical IVDD accounts for 13-25% of all cases. Ventral slot decompression provides access to ventral and centrally extruded or protruded disk material. However, procedures to remove dorsally or laterally displaced material are more difficult. This case series describes the use of perineural injection as a potential treatment option for dogs experiencing root-signature signs associated with lateralized disk material in the cervical spine. Five dogs underwent fluoroscopically guided perineural injection of methylprednisolone ± bupivacaine. Most patients experienced improvement in root-signature signs and remained pain free without the assistance of oral pain medication. These findings suggest the perineural injection of methylprednisolone ± bupivacaine represents a viable option for dogs with cervical lateralized disk material causing root-signature signs.
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    Thermotherapeutic enhancement of infusate distribution during convection enhanced delivery in the brain using fiber-optic microneedle devices
    Emch, Samantha (Virginia Tech, 2015-04-30)
    Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults and has a median survival of 13.4 months. Convection enhanced delivery (CED) has shown promise for the treatment of GBM by allowing intratumoral delivery of therapeutics, bypassing the blood brain barrier. A fiberoptic microneedle device (FMD) CED catheter enables simultaneous delivery of laser energy and therapeutic. The laser allows for heating of tissue in the region of infusion, called thermotherapy. Thermotherapy offers the advantages of increasing the volume of distribution (Vd) of the infusate, as well as facilitating intracellular penetration of the therapeutic. We hypothesize that heating of brain tissue will increase infusate Vd in ex vivo CED brain infusions. Methods: Formalin fixed mouse brains were infused by FMD-CED with Evans blue for 1 hour at 0.1 μl/min, at 22°C, 37°C and 42°C (n=4 brains/group). The Vd was determined and compared using one-way ANOVA. Results: FMD-CED performed at 42°C resulted in significantly higher mean Vd (4.90+2.2mm3; p =0.03) than those at 22°C (1.49+0.4 mm3), although no differences in Vd were observed between the other temperature groups. 42°C brains demonstrated interstitial and intracellular distribution, while rare intracellular distribution was noted in the other groups. Discussion: The Vd of FMD-CED infusions is facilitated by sub-lethal thermotherapy. This study indicates that thermotherapeutic enhancement of infusate Vd does not occur exclusively via vascular mechanisms. Thermotherapy facilitates advective-diffusion by decreasing interstitial fluid pressure and increasing transcellular fluid transport. These results were validated in a companion in vivo FMD-CED study in the rodent brain.
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    Titanium-Alloy Anchoring System as a Suitable Method of Extracapsular Repair
    Dominic, Christopher; Lanz, Otto I.; Muro, Noelle; Sawyere, Dominique; Aulakh, Karanvir; Pancotto, Theresa E.; Seda, David (Frontiers, 2020-12-17)
    Objective: To characterize the effect of a titanium-alloy anchoring system (TAS) on the motion of the cranial cruciate ligament (CrCL) deficient stifle. To compare the motion with the TAS to that of the CrCL-intact and CrCL-deficient stifle. Study Design: Each canine pelvic limb was mounted in a loading jig under 30% body weight. Motion data was collected using an electromagnetic tracking system at stifle angles of 125◦, 135◦, and 145◦ with the CrCL-intact, CrCL-deficient and the TAS applied. Results: Total translation of the CrCL-deficient stifle following the TAS was reduced, but remained greater than the CrCL-intact stifle at angles of 125◦, 135◦, and 145◦. Internal rotation of the TAS groups was greater than the CrCL-intact group at 145◦, but not 125◦ and 135◦. Varus motion of the TAS group was decreased compared to the CrCL-deficient group, but increased compared to the CrCL-intact group at angles of 125◦, 135◦, and 145◦. Conclusion: Total translation and internal rotation of the CrCL-deficient stifle following the TAS differed from that of the CrCL-intact stifle. However, the TAS reduced total translation and internal rotation of the tibia relative to the femur in the CrCL-deficient stifle to levels that may yield clinically acceptable results