The aim of this study is twofold: to characterize the epidemiology of idiopathic epilepsy (IE) in a large US primary care provider, and to investigate primary care veterinarians’ anti-seizure drugs (ASDs) prescribing practices. A multicenter retrospective study was conducted: Banfield Pet Hospital electronic medical records were searched (01/01/2020–31/12/2023) for dogs aged 6 months to 6 years at first recorded epileptic seizure, with normal general and neurological examinations and unremarkable blood analyses. To further support the IE diagnosis, only dogs prescribed ASDs were included. Signalment, ASDs name and dosing were recorded. Eight-hundred-fifty-three dogs met the inclusion criteria, corresponding to a prevalence of 0.03% (853/2,969,209 over 4 years). Labrador Retriever, Chihuahua and Siberian Husky were the most represented breeds. The median age at diagnosis was 3.3 years. Males accounted for 60.6% of cases. Phenobarbital (34.9%) and levetiracetam (31.3%) were the most prescribed first-line-ASDs, followed by zonisamide (22.9%) and potassium bromide (11.1%). Phenobarbital median maintenance dose was 2.5 mg/kg (IQR 2.2–3.0 mg/kg) per os (PO), with 99.3% of cases receiving it every 12 h. Extended-release levetiracetam was used in 97.4% of cases; the median dose was 29.7 mg/kg (IQR 24.1–34.6 mg/kg) PO, prescribed every 12 h in 87.7% of dogs. Zonisamide was prescribed at a median dose of 5.8 mg/kg (IQR 4.7–7.4 mg/kg) PO every 12 h (98.0%). Potassium bromide maintenance median daily dose was 29.9 mg/kg (IQR 24.0–38.4 mg/kg) PO with a once-daily administration in 83.3% of dogs. Phenobarbital serum concentration was monitored in 77.5% of cases, while bromide serum concentration was monitored in 31.6% of dogs. The estimated prevalence was lower than previous studies, possibly due to strict diagnostic inclusion criteria and data extraction limitations. Labrador Retrievers were the most affected breed, while other predisposed breeds were underrepresented among IE cases. Prescribing practices generally aligned with the ACVIM guidelines, suggesting good implementation of this knowledge in one of the largest US primary care providers. The variability in levetiracetam and potassium bromide dosing highlights the need for updated evidence-based dosing guidelines, while education on the value of therapeutic drug monitoring could support veterinary and pet-owner’s decision making in the management of IE.

Idiopathic epilepsy (IE) has a high prevalence and a severe clinical course in the Italian Spinone breed of dog. A genome-wide association study meta-analysis of 52 cases and 51 controls was conducted to identify genomic regions that may be involved with the development of IE. Subsequent to the meta-analysis, a set of 175 controls and an independent validation set of 23 cases and 23 controls were genotyped for SNPs showing suggestive association with IE to find variants exhibiting evidence of replicable association and to test the predictiveness of SNPs for IE status when combined in a weighted risk score. Although two regions showed statistically significant association with IE in the GWAS meta-analysis, and additional regions with suggestive association were identified, the findings were not emulated in the validation set. This is the first GWAS of IE in the Italian Spinone, and the findings suggest that IE in the breed is not monogenic and demonstrates the challenges when investigating a multigenic or complex inherited disease in a numerically small domesticated animal population.

Objectives This study aimed to describe the clinical characteristics, MRI findings, treatment and outcome in cats presumptively diagnosed with intramedullary intervertebral disc extrusions. Methods A retrospective review was conducted of medical records and MRI data from cats presumptively diagnosed with intramedullary intervertebral disc extrusions. Long-term outcome (⩾6 months) was assessed through medical records, questionnaires completed by the owners or both. Results A total of 12 cats met the inclusion criteria. All presented with peracute or acute clinical signs, with nine having confirmed (n = 3) or possible (n = 6) external trauma based on history, physical examination or MRI findings. Seven cats were ambulatory and five were non-ambulatory. Eight cats presented with urinary incontinence; none exhibited faecal incontinence. Neuroanatomical localisation included the T3–L3 (n = 7) and L4–S3 (n = 5) spinal cord segments. MRI showed an intramedullary intervertebral disc extrusion at the following sites: T12–T13 (n = 1), T13–L1 (n = 1), L1–L2 (n = 2), L2–L3 (n = 2), L4–L5 (n = 3) and L5–L6 (n = 3). All cats underwent treatment and were discharged after a median hospitalisation time of 4 days (range 3–14). All non-ambulatory cats with available follow-up information (4/5) regained ambulation by the time of the short-term (<6 weeks) or long-term (⩾6 months) assessment. Moreover, all cats either retained or regained urinary continence by the time of discharge, the short-term (<6 weeks) or the long-term (⩾6 months) assessment. Overall, nine cats achieved a successful outcome and were considered functional pets at the short-term (<6 weeks) and/or long-term (⩾6 months) follow-up. Two cats were lost to follow-up, and one cat had perceived persistent generalised discomfort. Conclusions and relevance Most cats presumptively diagnosed with an intramedullary intervertebral disc extrusion showed a favourable outcome with treatment in this study. This condition should be considered in cats presenting with peracute or acute signs of T3–L3 or L4–S3 spinal cord dysfunction, especially if there is a history or indication of trauma.

Cerebrospinal fluid (CSF) analysis is a common diagnostic tool in the investigation of neurological presentations. Whether its routine use after every brain magnetic resonance imaging (MRI) is warranted is debated amongst clinicians, and its usefulness after a normal MRI has not yet been examined. To investigate whether CSF analysis affected the final diagnosis in dogs and cats with suspected intracranial disease in the presence of unremarkable magnetic resonance imaging (MRI), clinical, imaging and laboratory records of dogs and cats with suspected intracranial disease, unremarkable MRI and CSF analysis were reviewed in this multi-center retrospective study. Of 593 animals, (533 dogs and 60 cats), 17 dogs (3%) had abnormal CSF, nine of these demonstrating pleocytosis (with or without elevated microprotein) and eight showing hyperproteinorrachia alone. In only five of these dogs (0.8% of the total cohort) was the final diagnosis and/or treatment meaningfully affected by CSF findings: three diagnosed with inflammatory brain conditions and two had undetermined diagnoses, with corticosteroids initiated following abnormal CSF results. No cats in this population had an abnormal CSF. All dogs with a diagnosis based on abnormal CSF results had an abnormal neurological examination. In this population, CSF analysis was unlikely to reveal an undiagnosed intracranial condition following an unremarkable brain MRI, particularly in dogs presenting with a normal neurological examination. In dogs presenting with an abnormal neurological examination or a high suspicion of inflammatory disease, CSF evaluation following normal MRI is more likely to be diagnostically valuable.

Abstract Background Peripheral nerve sheath tumors (PNSTs) are a group of neoplasms originating from Schwann cells or pluripotent cell of the neural crest. Therapeutic options and prognosis are influenced by their degree of malignancy and location. Hypothesis/Objectives Identify magnetic resonance imaging (MRI) features predictive of PNST histologic grade. Animals Forty‐four dogs with histopathological diagnosis of spinal PNSTs and previous MRI investigation. Methods A multicenter retrospective study including cases with (a) histopathologic diagnosis of PNST and (b) MRI studies available for review. Histologic slides were reviewed and graded by a board‐certified pathologist according to a modified French system (FNCLCC) for grading soft tissue sarcomas. The MRI studies were reviewed by 2 board‐certified radiologists blinded to the grade of the tumor and the final decision on the imaging characteristics was reached by consensus. Relationships between tumor grade and histological and MRI findings were assessed using statistical analysis. Results Forty‐four cases met inclusion criteria; 16 patients were PNSTs Grade 1 (low‐grade), 19 were PNSTs Grade 2 (medium‐grade), and 9 were PNSTs Grade 3 (high‐grade). Large volume (P = .03) and severe peripheral contrast enhancement (P = .04) were significantly associated with high tumor grade. Degree of muscle atrophy, heterogeneous signal and tumor growth into the vertebral canal were not associated with grade. Conclusions and Clinical Importance Grade of malignancy was difficult to identify based on diagnostic imaging alone. However, some MRI features were predictive of high‐grade PNSTs including tumor size and peripheral contrast enhancement.

EDITORIAL article Front. Vet. Sci., 10 February 2023Sec. Veterinary Neurology and Neurosurgery Volume 10 - 2023 | https://doi.org/10.3389/fvets.2023.1147908

Switching between brands of the same antiseizure medication has been associated with a loss of epileptic seizure control in people. No such reports are available in the veterinary literature. Here, we describe two cases in which client-owned dogs with idiopathic epilepsy experienced complications following phenobarbital brand switch, despite no change in the administered dosage. Both dogs had been on treatment with oral phenobarbital for at least 23 months without complications. Following brand switching, one dog became markedly sedated, ataxic and anorexic, and the other dog experienced severe cluster seizures. The measured serum phenobarbital concentrations were significantly altered from the previously measured pre-brand switching concentrations. Echoing what has been described in human medicine, these cases suggest that therapeutic complications can occur when switching phenobarbital brand in chronically treated dogs with idiopathic epilepsy. Such complications should be considered when modulating antiseizure treatment in dogs. The exact cause for the resulting complications is unclear.

IntroductionNeuroinflammation that occurs in the brain after stroke has been shown to be important to disease pathogenesis and outcomes. The aim of this study was to evaluate a large number of pro- and anti-inflammatory cytokines in dogs with clinically-confirmed, naturally occurring stroke.Materials and methodsFifteen dogs with a clinical diagnosis of ischemic stroke and ten healthy control dogs were included in the study. A multiplex immunoassay was utilized to evaluate cerebrospinal fluid for GM-CSF, IFN-γ, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, IP-10, CXCL1, MCP-1, and TNF-α.ResultsMean concentrations of CXCL1 (stroke-436 pg/ml, control-267 pg/ml, p = 0.01) and MCP-1 (stroke-196 pg/ml, control-66 pg/ml, p ≤ 0.0001) were significantly elevated in dogs with stroke when compared with control dogs. Location and type of infarct, duration of clinical signs, and use of anti-inflammatory medications were not associated with differences in cytokine concentration.DiscussionCXCL1 and MCP-1 may play a role in naturally occurring canine stroke and represent targets for future research.

The aims of this study are to gain insight on how primary care veterinarians in the UK diagnose and treat canine idiopathic epilepsy (IE) and what they perceive as challenges in the management of canine IE. Two hundred and thirty-five primary care veterinarians took part in this survey. The questionnaire asked about the type of practice the respondent worked in, any relevant post-graduate qualifications, how many years' experience they had in practice and the participant's canine IE caseload. Participants were asked how they diagnose canine IE, how they select antiseizure drugs (ASDs) and how they assess outcome. The questionnaire also explored which information sources they have access to for deciding on canine IE treatment, challenges that may be faced when managing these cases and areas in which more support can be provided. 94.5% of participants (n = 222/235) managed <10 canine IE cases in a year and 87.8% (n = 206/235) used phenobarbital as their first line ASD. The reported mean initial phenobarbital dose was 2.1 mg/kg (standard deviation = 0.71) every 12 h. When considering how closely participants aligned with IVETF guidelines on the topics of diagnosis, ASD initiation and outcome assessment, on average participants would score around half of the available points. 53.2% (n = 125/235) of respondents recommended neutering in canine IE and 46.8% (n = 110/235) did not. 53.2% (n = 125/235) did not recommend any additional treatments for canine IE beyond use of ASDs. 23.4% recommended Purina Neurocare diet (n = 55/235), 12.8% recommended environmental modification (n = 30/235), and 6.8% (n = 16/235) recommend medium chain triglyceride supplements. In this study participants found managing client expectations to be most challenging alongside canine IE emergency management. The main limitation of this study is the relatively low response rate and therefore the results may not reflect the entire small animal veterinary profession in the UK. However, the results of this study represent a starting point to inform educational resources and support strategies to improve quality care of canine IE in primary care.

There is limited information on canine spinal epidural empyema (SEE). The aim of this multicenter retrospective study is to describe the clinical presentation and outcome of dogs undergoing spinal surgery or conservative management for SEE. Forty-one dogs met the inclusion criteria; the SEE was treated surgically in 17 dogs and conservatively in 24 dogs. Two dogs underwent spinal surgery after failure of conservative management, meaning that 19 dogs in total had spinal surgery. Long-term (i.e., >6 months) follow-up was available in 35 dogs (19 conservatively treated and 16 surgically treated dogs). Recovery to a functional pet status was achieved in 15/19 (78.9%) conservatively treated and 12/16 (75%) surgically treated dogs. There was no significant difference (p = 1.000) in long-term outcome between conservatively and surgically treated dogs (78.9 and 75%, respectively). However, significantly more surgically treated dogs were non-ambulatory at presentation (9/17 vs. 5/24, p = 0.048) compared with conservatively treated dogs. This study suggests that conservative treatment may be appropriate for dogs with SEE that are ambulatory at presentation and that surgically treated dogs generally have good outcomes. Age may be a negative prognostic indicator as dogs with poor long-term outcomes were significantly older than dogs with a good long-term outcome (p = 0.048). A larger prospective randomized study may provide further insight on treatment and outcome of SEE in dogs.

OBJECTIVE:The aim of this study was to describe the surgical technique and outcomes of dogs with congenital thoracic vertebral body malformations (CTVBM) treated with unilateral vertebral distraction and stabilization with monocortical screws and polymethylmethacrylate (PMMA). STUDY DESIGN:Medical records of 10 client-owned dogs with CTVBM were retrospectively searched for signalment, history, neurological examination, neurological grade based on the modified Frankel scale (MFS), diagnostic method, CTVBM location, Cobb's angle, and vertebral canal angle (VCA), surgical procedure, complications and long-term follow-up. RESULTS:One dog suffered cardiac arrest 24 hours post-surgery and died. Median follow-up in nine dogs was 26.5 months (12-50 months). Cobb's angle improved from 33-83 to 10-46 degrees and the VCA ratio from 97-138 to 122-164 degrees. The MFS improved from 3 (n = 3)-4 (n = 7) to 4 (n = 2)-6 (n = 7). Seven dogs recovered full function. Nine dogs improved after surgery compared with preoperative status, recovering ambulation when lost or achieving normal neurological examination in seven cases. No complications were reported during the follow-up period (12-50 months). CONCLUSION:Unilateral transthoracic vertebral distraction and stabilization with monocortical screws and PMMA for treatment of compressive myelopathy due to CTVBM achieved long-term neurological improvement in 9 of 10 dogs.

Pigment-associated deafness is a common hereditary condition in a range of dog breeds. The aim of this study was to perform a genome-wide association analysis to investigate the genetic architecture of deafness in Australian Cattle Dogs. Genotypes for 104 757 polymorphisms in 216 dogs were available for analyses after quality control. A genomic relationship matrix was used in the mixed model analyses to account for polygenic effects, as we tested each polymorphism for its association with deafness, in a case/control experimental design. Three approaches were used to code the genotypes and test for additive, recessive and dominant SNP effects. The genome-wide association study analyses identified a clear association peak on CFA20, with the most significant SNPs on this chromosome (1.29 × 10-4 ) in the vicinity of MITF. Variants in MITF have been associated with white pigmentation in dogs and with deafness in humans and other species, supporting the premise that canine deafness is associated with variants in or near this gene. A recessive inheritance for the peak in CFA20 is possible given the significant results in the recessive model; however, the estimated heritability was low (4.54 × 10-5 ). Further validation, identification of variants and testing in other dog breeds are needed.

The Australian Cattle dog (ACD) is one of many breeds predisposed to congenital sensorineural deafness (CSD). The objective of this study was to estimate CSD prevalence and investigate any association with phenotype in the ACD in the UK. The database of the authors' institution was searched for ACD puppies undergoing brainstem auditory evoked response (BAER) testing for CSD screening (1999-2019). Inclusion criteria were BAER performed at 4-10 weeks of age, testing of complete litters and available phenotypic data. The age, sex, coat and iris colour, presence and location of face and body patches, hearing status and BAER- determined parental hearing status of each puppy were recorded. A multivariable mixed-effects logistic regression model was used to calculate odds ratios and 95% confidence intervals to determine whether any of these variables were significantly associated with CSD, while adjusting for clustering at litter level. Inclusion criteria were met for 524 puppies. Hearing was bilaterally normal in 464 puppies (88.6%). The prevalence of unilateral and bilateral CSD was 9.7% and 1.7%, respectively. On the basis of multivariable analysis, the presence of a pigmented face patch was the only phenotypic variable significantly associated with CSD, and was linked to a reduced risk of the condition. The prevalence was similar to that reported in an Australian population of ACDs. The key findings from this study were that overall CSD prevalence in the ACD population in the UK was 11.4%, and puppies with a face patch were at reduced risk of the condition.

Abstract Background The pathophysiology of changes in magnetic resonance imaging (MRI) detected after a seizure is not fully understood. Objective To characterize and describe seizure‐induced changes detected by MRI. Animals Eighty‐one client‐owned dogs diagnosed with idiopathic epilepsy. Methods Data collected retrospectively from medical records and included anatomical areas affected, T1‐, T2‐weighted and T2‐FLAIR (fluid‐attenuated inversion recovery) appearance, whether changes were unilateral or bilateral, symmetry, contrast enhancement, mass effect, and, gray and white matter distribution. Diffusion‐ and perfusion weighted maps were evaluated, if available. Results Seizure‐induced changes were T2‐hyperintense with no suppression of signal on FLAIR. Lesions were T1‐isointense (55/81) or hypointense (26/81), local mass effect (23/81) and contrast enhancement (12/81). The majority of changes were bilateral (71/81) and symmetrical (69/71). The most common areas affected were the hippocampus (39/81) cingulate gyrus (33/81), hippocampus and piriform lobes (32/81). Distribution analysis suggested concurrence between cingulate gyrus and pulvinar thalamic nuclei, the cingulate gyrus and parahippocampal gyrus, hippocampus and piriform lobe, and, hippocampus and parahippocampal gyrus. Diffusion (DWI) characteristics were a mixed‐pattern of restricted, facilitated, and normal diffusion. Perfusion (PWI) showed either hypoperfusion (6/9) or hyperperfusion (3/9). Conclusions and Clinical Importance More areas, than previously reported, have been identified that could incur seizure‐induced changes. Similar to human literature, DWI and PWI changes have been identified that could reflect the underlying metabolic and vascular changes.

Limited information is available on the long-term follow-up and seizure recurrence in dogs with reactive seizures due to suspected exogenous toxicity. The purpose of this study was to report the long-term follow-up of 13 dogs referred to a single referral hospital, diagnosed with reactive seizures and treated with a standardized levetiracetam protocol. All dogs received a loading levetiracetam dose of 60 mg/kg/IV once, followed by a maintenance dose of 20 mg/kg every 8 h as part of an open-label clinical study. Levetiracetam was withdrawn after a 6-months seizure-free period by reducing levetiracetam to 20 mg/kg every 12 h for a 4-week seizure-free period, followed by levetiracetam 20 mg/kg every 24 h for a 4-week seizure-free period, before levetiracetam treatment was stopped. No adverse effects of the treatment were reported. No dogs experienced any seizures after discharge or after levetiracetam withdrawal. Median follow-up time from time of discharge was of 78 months (=6 years 6 months). The result of this study supports the use of levetiracetam for treatment of reactive seizures due to exogenous substance intoxication. Moreover, our results do not support the need for long-term antiepileptic treatment in cases of reactive seizures due to exogenous intoxication.

Genotype imputation using a reference panel that combines high-density array data and publicly available whole genome sequence consortium variant data is potentially a cost-effective method to increase the density of extant lower-density array datasets. In this study, three datasets (two Border Collie; one Italian Spinone) generated using a legacy array (Illumina CanineHD, 173 662 SNPs) were utilised to assess the feasibility and accuracy of this approach and to gather additional evidence for the efficacy of canine genotype imputation. The cosmopolitan reference panels used to impute genotypes comprised dogs of 158 breeds, mixed breed dogs, wolves and Chinese indigenous dogs, as well as breed-specific individuals genotyped using the Axiom Canine HD array. The two Border Collie reference panels comprised 808 individuals including 79 Border Collies and 426 326 or 426 332 SNPs; and the Italian Spinone reference panel comprised 807 individuals including 38 Italian Spinoni and 476 313 SNPs. A high accuracy for imputation was observed, with the lowest accuracy observed for one of the Border Collie datasets (mean R-2 = 0.94) and the highest for the Italian Spinone dataset (mean R-2 = 0.97). This study's findings demonstrate that imputation of a legacy array study set using a reference panel comprising both breed-specific array data and multi-breed variant data derived from whole genomes is effective and accurate. The process of canine genotype imputation, using the valuable growing resource of publicly available canine genome variant datasets alongside breed-specific data, is described in detail to facilitate and encourage use of this technique in canine genetics.

Abstract Objective The aim of this study was to describe clinical and imaging features of thoracic vertebral canal stenosis secondary to the hypertrophy of the vertebral lamina and articular processes in screw-tail brachycephalic dog breeds, to evaluate the prevalence of the malformation in a large group of screw-tail dog breeds and to determine if degree of stenosis is associated with presence of neurological signs. Study Design This is a retrospective multicentric study. Materials and Methods Clinical records of 185 screw-tail brachycephalic dogs (French Bulldogs, English Bulldogs, Boston Terriers) and Pugs were reviewed. Ten dogs with neurological deficits secondary to thoracic vertebral canal stenosis diagnosed on magnetic resonance imaging were identified (Group 1). Neurologically normal dogs (n = 175) of the same breeds underwent computed tomographic imaging of the thoracic vertebral column for other medical reasons (Group 2). Cross-sectional measurements were used to calculate a stenotic ratio. Results Group 1 consisted of three French Bulldogs, six English Bulldogs and one Pug. Eight were males. Most dogs presented with progressive non-painful pelvic limbs ataxia and paresis. Twenty stenotic sites were identified with the most common being T4–T5. Three of ten dogs were treated surgically and all had a good long-term outcome. In Group 2, 33 of 175 dogs had one or more stenotic sites with the most common being T2–T3. The degree of the stenosis was significantly higher in Group 1 (p = 0.019). A stenotic ratio of 0.56 had sensitivity and specificity of 67% to differentiate between dogs with and without neurological signs. Conclusion Cranial thoracic vertebral canal stenosis is observed predominantly in young male Bulldogs, but not all stenoses are clinically relevant.

Case summary An 8-year-old neutered female domestic longhair cat was presented for investigation of a 48 h history of lethargy and pelvic limb ataxia. MRI of the spinal cord and vertebral column (C1 to sacrum) and brain was unremarkable. Lumbar cerebrospinal fluid analysis revealed pleocytosis and increased protein concentration. Thoracic radiographs and abdominal ultrasound were unremarkable. Anti-inflammatory doses of prednisolone were administered. Clinical deterioration occurred over the following 2 days, with the development of lower motor neuron deficits in both thoracic limbs. On repetition of the MRI, bilateral enlargement, T2-weighted hyperintensity, and marked contrast enhancement of the C7, C8 and T1 nerve roots, spinal nerves and brachial plexuses were observed. Infectious disease testing was negative. An immune-mediated inflammatory process was suspected and immunosuppressive doses of prednisolone were commenced. The clinical signs improved transiently, but marked deterioration occurred after 2 weeks. The patient was euthanased and a post-mortem examination was performed. A lymphocytic inflammatory infiltrate was detected in the C7, C8 and T1 nerve roots and dorsal root ganglia, and neoplastic plasma cells were identified in multiple organs. A diagnosis of non-cutaneous extramedullary plasmacytoma with multiorgan involvement and paraneoplastic ganglioradiculoneuritis was reached. Relevance and novel information Paraneoplastic ganglioradiculoneuritis in association with a plasma cell neoplasia has not been previously reported in the cat and should be considered as a differential diagnosis for cats with clinical or imaging evidence of an inflammatory process affecting the nerve roots, spinal nerves or brachial plexuses.