Evaluation of neurofilament light chain as a biomarker in dogs with structural and idiopathic epilepsy.

BACKGROUND: Neurofilament light chain (NfL) is a frequently used biomarker in humans for both diagnostic and therapeutic monitoring purposes in various neurologic diseases. HYPOTHESIS/OBJECTIVES: It was hypothesized that dogs with diagnosed structural epilepsy (SE) would have a significantly higher serum NfL concentrations compared to dogs with idiopathic epilepsy (IE). The secondary hypothesis was that dogs would have a significantly higher serum NfL concentrations when measured within 7 days after a seizure compared to being seizure-free for at least 30 days. ANIMALS: Fifty client-owned dogs presented to the neurology service for evaluation of seizures were enrolled. Fourteen dogs had SE and 36 dogs had IE. METHODS: Prospective cohort study performed on 52 serum samples obtained for NfL concentration measurement using single molecule array technology. RESULTS: The median serum concentration of NfL in dogs with SE was significantly higher (109 pg/mL; range, 11.4-741.3 pg/mL) than in dogs with IE (17.7 pg/mL; range, 5.8-188 pg/mL; Wilcoxon rank sum test, P = .001). No significant relationship was found between serum NfL concentration and time of sampling in relation to the most recent seizure in dogs with IE. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum NfL may serve as an adjunctive biomarker for the differentiation of SE and IE.

Magnetic resonance and computed tomographic imaging characteristics and potential molecular mechanisms of feline meningioma associated calvarial hyperostosis.

Meningiomas are the most common feline primary brain tumours, and calvarial hyperostosis (CH) is frequently documented in association with this neoplastic entity. The clinical significance of and mechanisms driving the formation of CH in cats with meningiomas are poorly understood, although tumour invasion into the skull and tumour production of cytokines and enzymes have been implicated as causes of CH in humans. This retrospective study investigated relationships between signalment, MRI or CT imaging features, histopathologic tumour characteristics, alkaline phosphatase (ALP) isoenzyme concentrations, tumour expression of matrix metalloproteinases (MMP)-2, MMP-9, and interleukin-6 (IL-6), and progression free survival times (PFS) following surgical treatment in 27 cats with meningiomas with (n = 15) or without (n = 12) evidence of CH. No significant differences in breed, age, sex, body weight, tumour grade, tumour volume, peritumoral edema burden, ALP isoenzyme concentrations, tumour Ki-67 labelling indices or MMP-2 or MMP-9 expression and activity, or PFS were noted between cats with or without CH. There was a trend towards higher serum (p = .06) and intratumoral (p = .07) concentrations of IL-6 in cats with CH, but these comparisons were not statistically significant. Histologic evidence of tumour invasion into bone was observed in 5/12 (42%) with CH and in no (0/6) cats without CH, although this was not statistically significant (p = .07). Tumour invasion into bone and tumour production of IL-6 may contribute to the formation of meningioma associated CH in cats, although larger studies are required to further substantiate these findings and determine their clinical relevance.

Clinical, Diagnostic, and Imaging Findings in Three Juvenile Dogs With Paraspinal Hyperesthesia or Myelopathy as a Consequence of Hemophilia A: A Case Report.

Three juvenile dogs presented with an acute onset of paraspinal hyperesthesia and/or neurologic deficits. These dogs underwent anesthesia for MRI and additional diagnostics. The thoracolumbar MRI in Dog 1 revealed an accumulation of T2-weighted (T2W) hyperintense, T1-weighted (T1W) iso- to hyperintense, contrast enhancing extradural material. The differential diagnoses were meningitis with secondary hemorrhage or empyema or late subacute hemorrhage. The initial cervical MRI in Dog 2 revealed T1W meningeal contrast enhancement suspected to be secondary to meningitis. A repeat MRI following neurologic decline after CSF sampling revealed a large area of T2W and T1W hyperintensity between fascial planes of the cervical musculature as well as T2W iso- to hyperintense and T1W iso- to hypointense extradural material at the level of C1 consistent with hemorrhage. The cervical MRI in Dog 3 revealed T2W hyperintense and T1W iso- to hypointense extradural compressive material consistent with hemorrhage. Dogs 1 and 2 underwent CSF sampling and developed complications, including subcutaneous hematoma and vertebral canal hemorrhage. Dog 3 underwent surgical decompression, which revealed a compressive extradural hematoma. In each case, a hemophilia panel including factor VIII concentration confirmed the diagnosis of hemophilia A. Dog 1 had a resolution of clinical signs for ~5 months before being euthanized from gastrointestinal hemorrhage. Dog 2 was euthanized due to neurologic decompensation following CSF sampling. Dog 3 did well for 2 weeks after surgery but was then lost to follow-up. This case series provides information on clinical signs, MRI findings, and outcome in 3 juvenile dogs with hemophilia A that developed neurologic deficits or paraspinal hyperesthesia secondary to spontaneous or iatrogenic vertebral canal hemorrhage. Hemophilia A should be considered as a differential in any young dog presenting with an acute onset of hyperesthesia with or without neurologic deficits. This diagnosis should be prioritized in young male dogs that have other evidence of hemorrhage on physical exam.

Crystal structures of FolM alternative dihydrofolate reductase 1 from Brucella suis and Brucella canis.

Members of the bacterial genus Brucella cause brucellosis, a zoonotic disease that affects both livestock and wildlife. Brucella are category B infectious agents that can be aerosolized for biological warfare. As part of the structural genomics studies at the Seattle Structural Genomics Center for Infectious Disease (SSGCID), FolM alternative dihydrofolate reductases 1 from Brucella suis and Brucella canis were produced and their structures are reported. The enzymes share ∼95% sequence identity but have less than 33% sequence identity to other homologues with known structure. The structures are prototypical NADPH-dependent short-chain reductases that share their highest tertiary-structural similarity with protozoan pteridine reductases, which are being investigated for rational therapeutic development.

Outcome of thoracolumbar surgical feline intervertebral disc disease.

OBJECTIVES: The aim of this study was to evaluate the outcome and prognosis of thoracolumbar feline intervertebral disc disease (IVDD) treated by surgical decompression. METHODS: This was a multi-institutional retrospective study evaluating the age, breed, sex, body weight, presenting complaint, neuroanatomic diagnosis at presentation, diagnostic imaging results, surgery performed and the overall outcome at discharge and at recheck. Bivariable associations between variables were assessed using the Kruskal-Wallis test (age and grade of IVDD at presentation) and Fisher's exact test (grade of IVDD at presentation and outcome). RESULTS: A total of 35 cats met the inclusion criteria for the study. The most frequently reported clinical sign was difficulty walking (54.2%). The majority of cats presented with an L4-S3 localization (57%). The most common site of intervertebral disc herniation (IVDH) was at L6-L7 (34%). The majority of feline patients that received surgery had a positive outcome at the time of discharge (62.5%; n = 20/32) and at the time of the 2-week recheck (91.3%; n = 21/23). No association was identified between the age of the patient and the grade of IVDD. No association was identified between the presenting grade of IVDD and the clinical outcome at the time of discharge or at the time of recheck evaluation. CONCLUSIONS AND RELEVANCE: Cats undergoing spinal decompressive surgery for thoracolumbar IVDH appear to have a favorable prognosis independent of the initial presenting grade of IVDD. A larger sample size and a longer length of follow-up is necessary to obtain statistical associations between the presenting grade of IVDD and overall clinical outcome.