Nimustine Treatment of 11 Cases of Canine Histiocytic Sarcoma.

The objective of this retrospective study was to report treatment outcomes in dogs with histiocytic sarcoma (HS) that were treated with nimustine (ACNU). This study evaluated data from 11 dogs including 5 with macroscopic tumors that were treated in the primary setting and 6 that underwent aggressive local therapy while being treated in the adjuvant setting. The median ACNU starting dose was 25 mg/m2 (range, 20-30 mg/m2; 3- to 5-wk intervals, 1-8 administrations). The median overall survival in the primary and adjuvant settings was 120 days (median progression-free survival [PFS], 63 days) and 400 days (median PFS, 212 days), respectively. Neutropenia was observed in eight cases (grade 1, n = 1; grade 2, n = 2; grade 3, n = 2; grade 4, n = 3) with nadir neutrophil count at 1 wk after ACNU administration. Mild gastrointestinal toxicity (grade 1-2) was observed in three cases. ACNU was well tolerated and showed a similar outcome to that seen for lomustine, which is a drug commonly used to treat canine HS, in terms of overall survival and PFS in the current study population. Further investigations will need to be undertaken to definitively determine if ACNU is an appropriate alternative to lomustine for the treatment of HS.

Molecular cloning and characterization of the family of feline leucine-rich glioma-inactivated (LGI) genes, and mutational analysis in familial spontaneous epileptic cats.

BACKGROUND: Leucine-rich glioma-inactivated (LGI) proteins play a critical role in synaptic transmission. Dysfunction of these genes and encoded proteins is associated with neurological disorders such as genetic epilepsy or autoimmune limbic encephalitis in animals and human. Familial spontaneous epileptic cats (FSECs) are the only feline strain and animal model of familial temporal lobe epilepsy. The seizure semiology of FSECs comprises recurrent limbic seizures with or without evolution into generalized epileptic seizures, while cats with antibodies against voltage-gated potassium channel complexed/LGI1 show limbic encephalitis and recurrent limbic seizures. However, it remains unclear whether the genetics underlying FSECs are associated with LGI family genes. In the present study, we cloned and characterized the feline LGI1-4 genes and examined their association with FSECs. Conventional PCR techniques were performed for cloning and mutational analysis. Characterization was predicted using bioinformatics software. RESULTS: The cDNAs of feline LGI1-4 contained 1674-bp, 1650-bp, 1647-bp, and 1617-bp open reading frames, respectively, and encoded proteins comprising 557, 549, 548, and 538 amino acid residues, respectively. The feline LGI1-4 putative protein sequences showed high homology with Homo sapiens, Canis familiaris, Bos taurus, Sus scrofa, and Equus caballus (92%-100%). Mutational analysis in 8 FSECs and 8 controls for LGI family genes revealed 3 non-synonymous and 14 synonymous single nucleotide polymorphisms in the coding region. Only one non-synonymous single nucleotide polymorphism in LGI4 was found in 3 out of 8 FSECs. Using three separate computational tools, this mutation was not predicted to be disease causing. No co-segregation of the disease was found with any variant. CONCLUSIONS: We cloned the cDNAs of the four feline LGI genes, analyzed the amino acid sequences, and revealed that epilepsy in FSEC is not a monogenic disorder associated with LGI genes.

Comparisons among MRI signs, apparent diffusion coefficient, and fractional anisotropy in dogs with a solitary intracranial meningioma or histiocytic sarcoma.

Although MRI has become widely used in small animal practice, little is known about the validity of advanced MRI techniques such as diffusion-weighted imaging and diffusion tensor imaging. The aim of this retrospective analytical observational study was to investigate the characteristics of diffusion parameters, that is the apparent diffusion coefficient and fractional anisotropy, in dogs with a solitary intracranial meningioma or histiocytic sarcoma. Dogs were included based on the performance of diffusion MRI and histological confirmation. Statistical analyses were performed to compare apparent diffusion coefficient and fractional anisotropy for the two types of tumor in the intra- and peritumoral regions. Eleven cases with meningioma and six with histiocytic sarcoma satisfied the inclusion criteria. Significant differences in apparent diffusion coefficient value (× 10-3 mm2 /s) between meningioma vs. histiocytic sarcoma were recognized in intratumoral small (1.07 vs. 0.76) and large (1.04 vs. 0.77) regions of interest, in the peritumoral margin (0.93 vs. 1.08), and in the T2 high region (1.21 vs. 1.41). Significant differences in fractional anisotropy values were found in the peritumoral margin (0.29 vs. 0.24) and the T2 high region (0.24 vs. 0.17). The current study identified differences in measurements of apparent diffusion coefficient and fractional anisotropy for meningioma and histiocytic sarcoma in a small sample of dogs. In addition, we observed that all cases of intracranial histiocytic sarcoma showed leptomeningeal enhancement and/or mass formation invading into the sulci in the contrast study. Future studies are needed to determine the sensitivity of these imaging characteristics for differentiating between these tumor types.

Retrospective epidemiological study of canine epilepsy in Japan using the International Veterinary Epilepsy Task Force classification 2015 (2003-2013): etiological distribution, risk factors, survival time, and lifespan.

BACKGROUND: Epilepsy is the most common neurological disease in veterinary practice. However, contrary to human medicine, epilepsy classification in veterinary medicine had not been clearly defined until recently. A number of reports on canine epilepsy have been published, reflecting in part updated proposals from the human epilepsy organization, the International League Against Epilepsy. In 2015, the International Veterinary Epilepsy Task Force (IVETF) published a consensus report on the classification and definition of canine epilepsy. The purpose of this retrospective study was to investigate the etiological distribution, survival time of dogs with idiopathic epilepsy (IdE) and structural epilepsy (StE), and risk factors for survival time, according to the recently published IVETF classification. We investigated canine cases with epilepsy that were referred to our teaching hospital in Japan during the past 10 years, and which encompassed a different breed population from Western countries. RESULTS: A total of 358 dogs with epilepsy satisfied our etiological study criteria. Of these, 172 dogs (48 %) were classified as IdE and 76 dogs (21 %) as StE. Of these dogs, 100 dogs (consisting of 65 with IdE and 35 with StE) were included in our survival study. Median survival time from the initial epileptic seizure in dogs with IdE and StE was 10.4 and 4.5 years, respectively. Median lifespan of dogs with IdE and StE was 13.5 and 10.9 years, respectively. Multivariable analysis demonstrated that risk factors for survival time in IdE were high seizure frequency (≥0.3 seizures/month) and focal epileptic seizures. CONCLUSIONS: Focal epileptic seizures were identified as a risk factor for survival time in IdE. Clinicians should carefully differentiate seizure type as it is difficult to identify focal epileptic seizures. With good seizure control, dogs with IdE can survive for nearly the same lifespan as the general dog population. Our results using the IVETF classification are similar to previous studies, although some features were noted in our Japanese canine population (which was composed of mainly small-breed dogs), including a longer lifespan in dogs with epilepsy and a larger percentage of meningoencephalomyelitis of unknown origin in dogs with StE.

Regulation of p16 gene expression by histone H3 acetylation in canine lymphoid tumor cell lines.

In order to investigate whether suppression of the p16 gene is mediated by histone H3 acetylation in 4 canine lymphoid tumor cell lines, the gene's acetylation status was examined. In 2 canine lymphoid tumor cell lines with low p16 mRNA expression (GL-1 and UL-1), the acetylation level was lower than that in CL-1 cells with high p16 mRNA expression. The expression of the p16 gene in these 2 cell lines was markedly restored after culture in the presence of a histone deacetylase inhibitors trichostatin A, indicating that p16 was inactivated by hypoacetylation. Findings obtained this study will add new insights and lead to the better understanding of the disease pathogenesis and future development of epigenetic therapeutic strategies.

Retrospective study of 540 cats with respiratory diseases in Japan (2003-2020).

BACKGROUND: Few epidemiological studies on respiratory medicine and the relationship between clinical signs and various respiratory diseases in cats have been reported. OBJECTIVES: This retrospective study aimed to investigate the prevalence and breed predisposition to feline respiratory diseases in Japan and determine the association between clinical signs, duration and type of respiratory diseases. METHODS: The medical records of cats with feline respiratory diseases were examined to obtain information on age, sex, breed, final diagnosis, clinical signs and duration. The odds ratios (ORs) and 95% confidence intervals were calculated to evaluate breed predispositions. Mann-Whitney U, Kruskal-Wallis and Dunn's tests were used to assess the duration of clinical signs. RESULTS: This study included 540 cats with 615 respiratory diagnoses. The American Shorthair breed was predisposed to bronchopneumonia (BP; OR: 5.0) and pulmonary tumour (PT; OR: 3.6), while the Russian Blue breed exhibited a predisposition to inflammatory lower airway diseases (OR: 3.4), BP (OR: 6.1) and interstitial lung diseases (OR: 11.1). Similarly, the Scottish Fold breed displayed predisposition to PTs (OR: 5.8). The duration of clinical signs among nasal diseases, nasopharyngeal diseases and lower tracheal/bronchial and pulmonary diseases differed significantly (p = 0.001, p = 0.012, p < 0.0001, respectively). CONCLUSIONS: The results suggest that some popular breeds in Japan are predisposed to feline respiratory diseases, especially the American Shorthair, Russian Blue and Scottish Fold breeds. The characteristics of occurrence, clinical signs and duration of each disease will aid in diagnosing, treating, preventing and elucidating the pathophysiology of feline respiratory disease.

Relationship between Respiratory Rate, Oxygen Saturation, and Blood Test Results in Dogs with Chronic or Acute Respiratory Disease: A Retrospective Study.

This study aimed to investigate the association of respiratory rate (RR), oxygen saturation (SpO2), and blood findings with respiratory disease in dogs and to compare the examination findings in the chronic and acute phases. Dogs that visited a veterinary referral hospital with respiratory symptoms were classified into the chronic disease group (GC), and those that visited the emergency veterinary hospital were classified into the acute disease group (GA). In total, 704 and 682 dogs were included in GC and GA, respectively. The RR and SpO2 were significantly higher and lower, respectively, in patients with lung disease compared to other disease sites in both groups. White blood cell counts were significantly increased in patients with lung and pleural diseases in both groups. Respiratory alkalosis and respiratory acidosis were most common in GC and GA, respectively. The C-reactive protein levels were elevated in both groups, primarily in patients with lung disease. Associations between the results of several tests for understanding and diagnosing respiratory conditions and diseases were recognized, and differences in the trends of the chronic and acute phases were clarified. These tools may be used as adjuncts to other tests for the diagnosis and monitoring of treatment responses.

Construction of diagnostic prediction model for canine nasal diseases using less invasive examinations without anesthesia.

Advanced imaging techniques under general anesthesia are frequently employed to achieve a definitive diagnosis of canine nasal diseases. However, these examinations may not be performed immediately in all cases. This study aimed to construct prediction models for canine nasal diseases using less-invasive examinations such as clinical signs and radiography. Dogs diagnosed with nasal disease between 2010 and 2020 were retrospectively investigated to construct a prediction model (Group M; GM), and dogs diagnosed between 2020 and 2021 were prospectively investigated to validate the efficacy (Group V; GV). Prediction models were created using two methods: manual (Model 1) and LASSO logistic regression analysis (Model 2). In total, 103 and 86 dogs were included in GM and GV, respectively. In Model 1, the sensitivity and specificity of neoplasia (NP) and sino-nasal aspergillosis (SNA) were 0.88 and 0.81 in GM and 0.92 and 0.78 in GV, respectively. Those of non-infectious rhinitis (NIR) and rhinitis secondary to dental disease (DD) were 0.78 and 0.88 in GM and 0.64 and 0.80 in GV, respectively. In Model 2, the sensitivity and specificity of NP and SNA were 0.93 and 1 in GM and 0.93 and 0.75 in GV, respectively. Those of NIR and DD were 0.96 and 0.89 in GM and 0.80 and 0.79 in GV, respectively. This study suggest that it is possible to create a prediction model using less-invasive examinations. Utilizing these predictive models may lead to appropriate general anesthesia examinations and treatment referrals.

Retrospective study of 1050 dogs with respiratory symptoms in Japan (2005-2020).

BACKGROUND: Few studies have investigated the incidence of respiratory diseases based on anatomical sites or the relationship between breed and these diseases. OBJECTIVE: The objective of this study was to investigate the prevalence of canine respiratory diseases among dogs in Japan, with relationship to the breed. METHODS: We retrospectively reviewed the medical records of dogs with respiratory symptoms and calculated the odds ratio (OR) to evaluate the relationship between breed and disease. RESULTS: A total of 1050 dogs with respiratory symptoms were included in this study. Miniature dachshunds were the most common breed affected by respiratory diseases. Among tracheobronchial diseases, there was a significant association between some small breeds and tracheobronchial collapse, miniature dachshunds (OR: 4.44, 8.43, 95% confidence interval [CI]: 3.17-6.22, 4.33-16.0) and chronic bronchitis and bronchiectasis. Among nasal diseases, miniature dachshunds (OR: 27.2, 95% CI: 16.8-44.8) and golden retrievers (OR: 21.0, 95% CI: 6.43-69.3) were the most affected by non-infectious rhinitis and nasal aspergillosis, respectively. Brachycephalic obstructive airway syndrome was the most common disease among pharyngeal and laryngeal diseases, with a relationship with breed being found in some brachycephalic breeds, and Pomeranians (OR: 2.7, 95% CI: 1.42-5.17). CONCLUSIONS: Respiratory diseases in dogs are strongly correlated with popular breeds in Japan. Miniature dachshunds, in particular, are associated with many respiratory diseases, which may differ from international reports. Thus, this result may help in the early detection, prevention, treatment, and elucidation of the pathophysiology of canine respiratory diseases.

Retrospective study of feline tracheal mass lesions.

OBJECTIVES: This multicentre, retrospective observational study aimed to describe the clinical presentation, diagnostic methods, treatment and outcomes of cats with tracheal masses. METHODS: Eighteen cats from five academic or secondary/tertiary animal hospitals were included. RESULTS: The median age at diagnosis was 10.7 years (mean 9.5; range 1-17). There were nine castrated males, seven spayed females, one intact male and one intact female. Fourteen (78%) were domestic shorthairs, one (6%) was an Abyssinian, one (6%) was an American Shorthair, one (6%) was a Bengal and one (6%) was a Scottish Fold. The most common presenting complaints included chronic respiratory distress or dyspnoea (n = 14), followed by wheezing/gagging (n = 12), coughing (n = 5) and voice changes (n = 5). There was cervical tracheal involvement in 16/18, and two showed involvement of the intrathoracic trachea. The following methods were used for diagnosis: ultrasound-guided fine-needle biopsy (UG-FNB) and cytology (n = 8), bronchoscopic forceps biopsy and histopathology (n = 5), surgical resection and histopathology (n = 3), forceps biopsy via an endotracheal tube (n = 1) and histology of tissue sputtered from a cough (n = 1). Lymphoma was most often diagnosed (n = 15), followed by adenocarcinoma (n = 2) and squamous cell carcinoma (n = 1). Most lymphoma cases received chemotherapy with or without radiation according to various protocols, and partial (n = 5) or complete responses (n = 8) were noted. Kaplan-Meier survival data for cats with lymphoma revealed a median survival time of 214 days (95% confidence interval >149 days), which was significantly longer than that of other types of tumours (21 days). CONCLUSIONS AND RELEVANCE: Lymphoma was the most prevalent diagnosis, and showed a good response to chemotherapy with or without radiation therapy. Various diagnostic procedures were performed, and UG-FNB and cytology are good diagnostic procedures for cervical tracheal lesions. Owing to the variety of treatment protocols at different centres, it was impossible to compare outcomes.

Efficacy of chemotherapy and palliative hypofractionated radiotherapy for cats with nasal lymphoma.

Nasal lymphoma (NL) is the most common nasal tumor in cats, and radiotherapy, chemotherapy, or a combination of these treatments have been described as the treatment for this disease. However, the previous studies included various machines and protocols of radiotherapy. Therefore, we aimed to retrospectively compare the prognosis among cases treated with palliative hypofractionated radiotherapy, chemotherapy, and a combination of them with united machine and protocol of radiotherapy. When compared overall survival and progression free survival, there was no significant difference among these three groups. The data of this study suggested that similar efficacy could be achieved by palliative hypofractionated radiotherapy, chemotherapy, or a combination of them.

Expression of DEP Domain-Containing 1B in Canine Lymphoma and Other Types of Canine Tumours.

Canine lymphoma is the most common haematological malignancy in dogs and is typically treated with multidrug chemotherapy. Most cases are at risk of relapse after several courses of chemotherapy and the oncogenic mechanism remains unknown. This study was aimed at identifying genes expressed in canine lymphoma by cDNA microarray. We found elevated expression of Dishevelled, EGL-10 and pleckstrin (DEP) domain-containing 1B (DEPDC1B) in canine lymphoma cells compared with cells and tissues from healthy dogs. Canine DEPDC1B protein was detected in 13 of 41 lymphoma specimens by immunohistochemistry, but was not detected in lymph nodes from normal dogs. Immunoreactive DEPDC1B protein was also detected in several other types of canine tumour. This is the first report documenting the association of DEPDC1B with canine cancer and the results suggest that DEPDC1B might serve as a potential marker or therapeutic target for canine malignancies.

Comparison of Canine and Feline Meningiomas Using the Apparent Diffusion Coefficient and Fractional Anisotropy.

Meningiomas are the most common intracranial tumor in dogs and cats, and their surgical resection is often performed because they are present on the brain surface. Typical meningiomas show comparatively characteristic magnetic resonance imaging findings that lead to clinical diagnosis; however, it is necessary to capture not only macroscopic changes but also microstructural changes to devise a strategy for surgical resection and/or quality of removal. To visualize such microstructural changes, diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) have been used in human medicine. The aim of this retrospective study was to investigate the different characteristics of the apparent diffusion coefficient (ADC) from DWI and fractional anisotropy (FA) from DTI of meningioma between dogs and cats. Statistical analyses were performed to compare ADC and FA values between the intratumoral or peritumoral regions and normal-appearing white matter (NAWM) among 13 dogs (13 lesions, but 12 each in ADC and FA analysis) and six cats (seven lesions). The NAWM of cats had a significantly lower ADC and higher FA compared to dogs. Therefore, for a comparison between dogs and cats, we used ADC and FA ratios that were calculated by dividing the subject (intra- or peritumoral) ADC and FA values by those of NAWM on the contralateral side. Regarding the intratumoral region, feline meningiomas showed a significantly lower ADC ratio and higher FA ratio than canine meningiomas. This study suggested that ADC and FA may be able to distinguish a meningioma that is solid and easy to detach, like as typical feline meningiomas.

Measurement of the concentration of serum soluble interleukin-2 receptor alpha chain in dogs with lymphoma.

Soluble interleukin-2 receptor (sIL-2r) is released directly from the surface of lymphocytes expressing interleukin-2 receptor alpha chain (CD25), and its serum concentration has been found to reflect the prognosis of human lymphoproliferative malignancies. In this study, we demonstrated the presence of sIL-2r in canine serum and developed a specific sandwich enzyme-linked immunosorbent assay (ELISA) to quantify the concentration of canine serum sIL-2r. In the immunoprecipitation (IP) assay, CD25 protein weighing approximately 45 kDa was detected in canine serum, smaller than the membrane-bound CD25 (approximately 55 kDa). To measure the concentration of serum sIL-2r in dogs, an ELISA system was developed. Serum sIL-2r levels were significantly higher in dogs with multicentric high-grade B-cell lymphoma before therapy than that in healthy dogs. Serum sIL-2r concentration was also found to be elevated in a proportion of dogs with other types of lymphoma. Changes in serum sIL-2r levels generally paralleled the changes in mass and lymph node size in dogs with high-grade B-cell lymphoma. This study demonstrated that serum sIL-2r level would be a marker to monitor tumour growth and regression in canine lymphoma.

Dynamic pharyngeal collapse in three cats with different pharyngeal pathology.

Dynamic pharyngeal collapse (PC) is a rarely reported condition in cats defined as the partial or complete collapse of the pharyngeal lumen during inspiration. Herein, we report the imaging findings and clinical features of three cats with dynamic PC. Lateral radiograph of the head was insufficient to detect dynamic PC, but fluoroscopy in conscious cats revealed dynamic PC. Magnetic resonance imaging was not helpful to reveal dynamic PC and underlying diseases. We obtained biopsy samples from the irregular nasopharyngeal mucosal membrane through endoscopy in two of the three cases and high-grade B-cell lymphoma was histopathologically diagnosed. In feline cases with abnormal upper respiratory sounds, dynamic PC should be considered, and fluoroscopy is the imaging technique of choice to diagnose the condition.

Efficacy of zonisamide on interictal electroencephalography in familial spontaneous epileptic cats.

Objectives The effectiveness of zonisamide (ZNS) against spontaneous epilepsy in cats has not yet been described. The purpose of this study was to investigate the effect of ZNS on interictal paroxysmal discharges (PDs) using scalp electroencephalography (EEG) in familial spontaneous epileptic cats (FSECs). Methods Eight FSECs were evaluated (six males and two females). Scalp EEG measurements were performed once a week for 3 weeks before ZNS administration (Pre-ZNS). Thereafter, administration of ZNS was started and an adjustment period was instituted until the drug in plasma achieved the steady state. When ZNS in plasma was confirmed to be within 10-40 µg/ml, scalp EEG measurements were performed once a week for 3 weeks (Post-ZNS). The number of PDs (counts/min) were compared between Pre-ZNS and Post-ZNS treatment. Results The median number of PDs for Pre-ZNS and Post-ZNS were 0.43/min (0.13-0.82/min) and 0.28/min (0.07-0.87/min), respectively. The number of PDs Post-ZNS was significantly reduced compared with Pre-ZNS ( P = 0.02). Conclusions and relevance This study showed that ZNS, within the recommended therapeutic range suggested for use in humans and dogs (10-40 µg/ml), reduced the number of PDs recorded on EEG in FSECs that are considered a model for cats with idiopathic epilepsy. Although phenobarbital is the antiepileptic drug of choice for epileptic cats, the results of this research provide evidence to support the use of ZNS in cats with phenobarbital-resistant epilepsy or for cats that cannot use phenobarbital due to adverse side effects.

Statistical Structural Analysis of Familial Spontaneous Epileptic Cats Using Voxel-Based Morphometry.

Voxel-based morphometry (VBM) based on high resolution three-dimensional data of magnetic resonance imaging has been developed as a statistical morphometric imaging analysis method to locate brain abnormalities in humans. Recently, VBM has been used for human patients with psychological or neurological disorders such as Alzheimer's disease, Parkinson's disease, and epilepsy. Traditional volumetry using region of interest (ROI) is performed manually and the observer needs detailed knowledge of the neuroanatomy having to trace objects of interest on many slices which can cause artificial errors. In contrast, VBM is an automatic technique that has less observer biases compared to the ROI method. In humans, VBM analysis is performed in patients with epilepsy to detect accurately structural abnormalities. Familial spontaneous epileptic cats (FSECs) have been developed as an animal model of mesial temporal lobe epilepsy. In FSECs, hippocampal asymmetry had been detected using three-dimensional magnetic resonance (MR) volumetry based on the ROI method. In this study, we produced a standard template of the feline brain and compared FSECs and healthy cats using standard VBM analysis. The feline standard template and tissue probability maps were created using 38 scans from 14 healthy cats. Subsequently, the gray matter was compared between FSECs (n = 25) and healthy controls (n = 12) as group analysis and between each FSEC and controls as individual analysis. The feline standard template and tissue probability maps could be created using the VBM tools for humans. There was no significant reduction of GM in the FSEC group compared to the control group. However, 5/25 (20%) FSECs showed significant decreases in the hippocampal and/or amygdaloid regions in individual analysis. Here, we established the feline standard templates of the brain that can be used to determine accurately abnormal zones. Furthermore, like MR volumetry, VBM identified morphometric changes in the hippocampus and/or amygdala in some FSECs.

Neuropathologic features of the hippocampus and amygdala in cats with familial spontaneous epilepsy.

OBJECTIVE To investigate epilepsy-related neuropathologic changes in cats of a familial spontaneous epileptic strain (ie, familial spontaneous epileptic cats [FSECs]). ANIMALS 6 FSECs, 9 age-matched unrelated healthy control cats, and 2 nonaffected (without clinical seizures)dams and 1 nonaffected sire of FSECs. PROCEDURES Immunohistochemical analyses were used to evaluate hippocampal sclerosis, amygdaloid sclerosis, mossy fiber sprouting, and granule cell pathological changes. Values were compared between FSECs and control cats. RESULTS Significantly fewer neurons without gliosis were detected in the third subregion of the cornu ammonis (CA) of the dorsal and ventral aspects of the hippocampus as well as the central nucleus of the amygdala in FSECs versus control cats. Gliosis without neuronal loss was also observed in the CA4 subregion of the ventral aspect of the hippocampus. No changes in mossy fiber sprouting and granule cell pathological changes were detected. Moreover, similar changes were observed in the dams and sire without clinical seizures, although to a lesser extent. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that the lower numbers of neurons in the CA3 subregion of the hippocampus and the central nucleus of the amygdala were endophenotypes of familial spontaneous epilepsy in cats. In contrast to results of other veterinary medicine reports, severe epilepsy-related neuropathologic changes (eg, hippocampal sclerosis, amygdaloid sclerosis, mossy fiber sprouting, and granule cell pathological changes) were not detected in FSECs. Despite the use of a small number of cats with infrequent seizures, these findings contributed new insights on the pathophysiologic mechanisms of genetic-related epilepsy in cats.

Changes in the interictal and early postictal diffusion and perfusion magnetic resonance parameters in familial spontaneous epileptic cats.

OBJECTIVE: The familial spontaneous epileptic cat (FSEC) is thought to be a good genetic model of mesial temporal lobe epilepsy. In the current study, cerebral diffusion and perfusion magnetic resonance imaging (MRI) were used to confirm the functional deficit zone in the FSEC and evaluate the effect of a single seizure on different brain regions. METHODS: Six FSECs and six healthy control cats were used in this study. MRI was performed in the interictal state (resting state for control) and postictal state immediately after the vestibular stimulation-induced generalized epileptic seizure (control cats received the same stimulation as the FSECs). The apparent diffusion coefficient (ADC), fractional anisotropy and perfusion parameters (i.e., relative regional cerebral blood volume (rCBV), relative regional cerebral blood flow (rCBF), and relative regional mean transit time (rMTT)) were measured in the hippocampus, amygdala, thalamus, and gray and white matter. RESULTS: In the interictal state, the rCBV and rMTT in the hippocampus was significantly decreased in FSECs, compared to the control. In the postictal state, FSECs had a significantly decreased ADC and an increased rCBV, rCBF, and rMTT in the hippocampus, and an increased rMTT in the amygdala, compared to the interictal state. CONCLUSION: This study showed that FSECs had interictal hypoperfusion in the hippocampus, and postictal hypodiffusion and hyperperfusion in the hippocampus and/or amygdala. These findings suggested that the hippocampus and/or amygdala act as the functional deficit and expanded seizure-onset zones in FSECs.

Interictal diffusion and perfusion magnetic resonance imaging features of cats with familial spontaneous epilepsy.

OBJECTIVE To evaluate the usefulness of diffusion and perfusion MRI of the cerebrum in cats with familial spontaneous epilepsy (FSECs) and identify microstructural and functional deficit zones in affected cats. ANIMALS 19 FSECs and 12 healthy cats. PROCEDURES Diffusion-weighted, diffusion tensor, and perfusion-weighted MRI of the cerebrum were performed during interictal periods in FSECs. Imaging findings were compared between FSECs and control cats. Diffusion (apparent diffusion coefficient and fractional anisotropy) and perfusion (relative cerebral blood volume [rCBV], relative cerebral blood flow [rCBF], and mean transit time) variables were measured bilaterally in the hippocampus, amygdala, thalamus, parietal cortex gray matter, and subcortical white matter. Asymmetry of these variables in each region was also evaluated and compared between FSECs and control cats. RESULTS The apparent diffusion coefficient of the total amygdala of FSECs was significantly higher, compared with that of control cats. The fractional anisotropy of the right side and total hippocampus of FSECs was significantly lower, compared with that of control cats. The left and right sides and total hippocampal rCBV and rCBF were significantly lower in FSECs than in control cats. The rCBV and rCBF of the parietal cortex gray matter in FSECs were significantly lower than in control cats. CONCLUSIONS AND CLINICAL RELEVANCE In FSECs, diffusion and perfusion MRI detected microstructural changes and hypoperfusion (lowered function) in the cerebrum during interictal periods from that of healthy cats. These findings indicated that diffusion and perfusion MRI may be useful for noninvasive evaluation of epileptogenic foci in cats.