Feline infectious peritonitis (FIP) is caused by a mutant biotype of the feline enteric coronavirus. The resulting FIP virus (FIPV) commonly causes central nervous system (CNS) and ocular pathology in cases of noneffusive disease. Over 95% of cats with FIP will succumb to disease in days to months after diagnosis despite a variety of historically used treatments. Recently developed antiviral drugs have shown promise in treatment of nonneurological FIP, but data from neurological FIP cases are limited. Four cases of naturally occurring FIP with CNS involvement were treated with the antiviral nucleoside analogue GS‐441524 (5‐10 mg/kg) for at least 12 weeks. Cats were monitored serially with physical, neurologic, and ophthalmic examinations. One cat had serial magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis (including feline coronavirus [FCoV]) titers and FCoV reverse transcriptase [RT]‐PCR) and serial ocular imaging using Fourier‐domain optical coherence tomography (FD‐OCT) and in vivo confocal microscopy (IVCM). All cats had a positive response to treatment. Three cats are alive off treatment (528, 516, and 354 days after treatment initiation) with normal physical and neurologic examinations. One cat was euthanized 216 days after treatment initiation following relapses after primary and secondary treatment. In 1 case, resolution of disease was defined based on normalization of MRI and CSF findings and resolution of cranial and caudal segment disease with ocular imaging. Treatment with GS‐441524 shows clinical efficacy and may result in clearance and long‐term resolution of neurological FIP. Dosages required for CNS disease may be higher than those used for nonneurological FIP.
Background Glioma-associated microglia/macrophage (GAM) markedly influence glioma progression. Under the influence of transforming growth factor beta (TGFB), GAM are polarized toward a tumor-supportive phenotype. However, neither therapeutic targeting of GAM recruitment, nor TGF Beta (TGFB) signaling demonstrated efficacy in glioma patients despite efficacy in preclinical models, underscoring the need for a comprehensive understanding of the TGFB/GAM axis. Spontaneously occurring canine gliomas share many features with human glioma and provide a complementary translational animal model for further study. Given the importance of GAM and TGFB in human glioma, the aims of this study were to further define the GAM-associated molecular profile and the relevance of TGFB signaling in canine glioma that may serve as the basis for future translational studies. Methods GAM morphometry, levels of GAM-associated molecules, and the canonical TGFB signaling axis were compared in archived samples of canine astrocytomas versus normal canine brain. Further, the effect of TGFB on the malignant phenotype of canine astrocytoma cells was evaluated. Results GAMs diffusely infiltrated canine astrocytomas. GAM density was increased in high-grade tumors that correlated with a pro-tumorigenic molecular signature and up-regulation of the canonical TGFB signaling axis. Moreover, TGFB1 enhanced migration of canine astrocytoma cells in vitro. Conclusions Canine astrocytomas share a similar GAM-associated immune landscape with human adult glioma. Our data also support a contributing role for TGFB1 signaling in the malignant phenotype of canine astrocytoma. These data further support naturally occurring canine glioma as a valid model for investigation of GAM-associated therapeutic strategies for human malignant glioma.
OBJECTIVE To evaluate neurological tests and expected results in inland bearded dragons (Pogona vitticeps) and generate recommendations for bearded dragon–specific neurological examination. ANIMALS 26 healthy adult inland bearded dragons. PROCEDURES A complete neurological examination utilizing tests described in both mammals and reptiles was performed on each lizard, and test feasibility and outcome were recorded. RESULTS Tests with poor feasibility included oculocardiac reflex (successfully completed in 62% [16/26] of animals) and voluntary ambulation and swallowing by use of a food item (0% [0/26] of animals). Tests with outcomes considered abnormal in mammals but attributable to normal bearded dragon behavior included head position (head tilt present in 12% [3/26]) and head movement (head bob present in 4% [1/26]). Many tests had absent or inconsistent outcomes, including menace response (present in 19% [5/26]), proprioceptive positioning (present in 4% [1/26] in the thoracic limbs and 0% [0/26] in the pelvic limbs), vent reflex (present in 27% [7/26]), and myotatic reflexes (biceps present in 8% [2/26]; patellar, gastrocnemius, and triceps present in 0% [0/26]). Extensor postural thrust was absent in all successfully tested animals, but a novel reflex termed the caudal thoracic extensor reflex was noted instead in all observed animals (100% [21/21]). CLINICAL RELEVANCE Tests with poor feasibility or inconsistent outcomes should have low priority or be excluded from neurological examinations of inland bearded dragons. Normal behaviors should be considered for head position and movement. A bearded dragon–specific neurological examination protocol derived from these findings is described and recommended in order to decrease stress and improve neurolocalization.
Objective: To describe the clinical signs, electroencephalographic (EEG) findings, treatment, and outcome in a dog after successful resuscitation from out-of-hospital cardiopulmonary arrest (OHCA) induced by pentobarbital intoxication.
Background Serum phosphorylated neurofilament‐heavy chain (pNF‐H) has not been longitudinally evaluated in dogs that develop progressive myelomalacia (PMM) after Type I intervertebral disc herniation (IVDH). Objectives To determine if serum pNF‐H concentrations would predict outcome of neuroligical disease in dogs with acute, severe thoracolumbar myelopathy secondary to Type I IVDH. Animals Thirty‐nine client‐owned dogs with thoracolumbar myelopathy secondary to IVDH. Methods Prospective controlled cohort study. Serum was collected from dogs undergoing hemilaminectomy at multiple timepoints. Final neurological status was established at 12 months and groups were stratified accordingly. Comparisons between outcome and pNF‐H concentration at each timepoint was examined using Kruskal‐Wallis analysis of variance on ranks and receiver operator characteristics curve analysis. Results Median serum pNF‐H concentrations were not significantly different between deep pain negative dogs that did or did not recover at any timepoint (baseline: 0.37 ng/mL [0‐0.9 ng/mL] vs 0 ng/mL [0‐0.9 ng/mL], P > 1; 24 hours: 1.25 ng/mL [0.35‐7.23 ng/mL] vs 1.53 ng/mL [0‐11.94 ng/mL], P > 1; 48 hours: 1.22 ng/mL [0.63‐6.62 ng/mL] vs 2.12 ng/mL [0‐20.72 ng/mL], P > 1; 72 hours: 2.77 ng/mL [1.33‐6.62 ng/mL] vs 16.69 ng/mL [4.02‐40.12 ng/mL], P > 1). Dogs that developed PMM had significantly higher serum pNF‐H concentrations after surgery compared to all other cohorts at 24 hours: 39.88 ng/mL (25.74‐50.68 ng/mL); P < .05 and 72 hours: 223.9 ng/mL (155.4‐263.7 ng/mL); P < .05. A serum pNF‐H concentration ≥31.39 ng/mL was 83.33% sensitive and 100% specific for identifying PMM in this cohort. Conclusions and Clinical Importance Serum pNF‐H is a promising biomarker for antemortem diagnosis of PMM in dogs with acute, severe thoracolumbar myelopathy secondary to Type I IVDH.
Case summary A 10-year-old Maine Coon cat was presented for acute onset seizures and cerebrothalamic signs. An intracranial mass, suspected to be a meningioma, was diagnosed on MRI and surgically excised. Histopathology appeared consistent with an atypical meningioma. However, following rapid regrowth of the neoplasm, the patient was humanely euthanized 3 months later. On post-mortem histopathology, the neoplasm was diagnosed as a grade III anaplastic gemistocytic astrocytoma. Relevance and novel information Gemistocytic astrocytomas are rare brain tumors in the feline patient. This case represents the first report of a feline grade III anaplastic gemistocytic astrocytoma in the cerebrum of a cat with surgical excision and recurrence. The challenging nature of ante-mortem diagnosis and the guarded prognosis, despite surgical intervention, are presented in this report.
Objective To investigate emergency clinicians’ comfort level in assessing neurological emergencies and to identify opportunities to foster enhanced training of clinical neurology in the emergency room. Design Internet‐based survey. Setting University teaching hospitals and private referral centers. Subjects One hundred and ninety‐two emergency and critical care specialists and resident trainees (ECC) and 104 neurology specialists and resident trainees (NEUR) in clinical practice. Interventions An internet‐based survey was distributed via veterinary professional organizations’ listserves and message boards and responses were collected between March and April 2020. ECC completed a survey evaluating stress levels associated with neurological emergencies, confidence with neurological examinations, and neuroanatomical localization. NEUR completed a similar survey to report their perception of their ECC colleagues’ confidence in the assessment of neurological cases. Chi‐square and Mann–Whitney U‐tests were used to compare categorical responses and confidence scores between groups. P < 0.002 was considered significant. Measurements and Main Results Fifty‐two percent of ECC found neurological emergencies slightly challenging, whereas 85% of NEUR found them moderately to extremely challenging for ECC (P < 0.0001). ECC's median self‐reported confidence score in performing a neurologic examination on a scale of 0–100 was 75 (interquartile range [IQR], 27), while NEUR reported a median ECC confidence of 44 (IQR, 25; P < 0.0001). Median self‐reported ECC confidence in localizing intracranial, spinal, and neuromuscular disease was 67 (IQR, 40), 88 (IQR, 21), and 60 (IQR, 37), respectively, which was significantly higher than median NEUR‐reported ECC confidence of 35 (IQR, 38), 51 (IQR, 31), and 18 (IQR, 20), respectively (all P < 0.0001). Following case transfer, 34% of ECC received NEUR feedback in >75% of cases. Conclusions Noticeable discrepancies between ECC and NEUR perceptions of ECC clinical confidence were seen, while no firm evidence of neurophobia could be inferred. Improvements in interdepartmental communication and teaching of clinical neurology may be warranted.
Bromethalin toxicosis is an increasingly common clinical presentation in dogs that may be fatal depending on the extent of intoxication. Antemortem diagnosis of bromethalin toxicosis was achieved in three dogs by demonstration of the active metabolite desmethylbromethalin in fat or serum. Magnetic resonance imaging (MRI) findings were consistent with a diffuse leukoencephalopathy with restricted diffusion and prominent involvement of the corticospinal motor tracts on T2-weighted and diffusion-weighted sequences. Imaging findings were confirmed in one non-surviving dog at necropsy. Resolution of MRI abnormalities was demonstrated in one surviving dog that was consistent with the associated resolution of clinical signs. Initial findings in these dogs support further investigation of specific MRI patterns in cases of leukoencephalopathy to aid differential diagnosis. While antemortem detection of bromethalin and its metabolites confirms exposure, quantitation may be informative as a prognostic biomarker.
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