Suspected malnutrition-induced reversible feline skin fragility syndrome in a cat with congenital axial deformities.

A stray cat, an intact female Japanese domestic shorthair cat of unknown age (suspected to be a young adult), was rescued. The cat was lethargic and thin and had marked skin fragility, delayed wound healing without skin hyperextensibility, and hind limb proprioceptive ataxia and paresis. Survey radiography, computed tomography, and magnetic resonance imaging revealed congenital vertebral anomalies, including thoracolumbar transitional vertebrae, scoliosis resulting from a thoracic lateral wedge-shaped vertebra, and a kinked tail, and a dilated spinal cord central canal. Through nutritional support, the cat's general condition normalized, followed by a gradual and complete improvement of skin features. Whole-genome sequencing was completed; however, no pathogenic genetic variant was identified that could have caused this phenotype, including congenital scoliosis. A skin biopsy obtained 7 y after the rescue revealed no remarkable findings on histopathology or transmission electron microscopy. Based on clinical course and microscopic findings, malnutrition-induced reversible feline skin fragility syndrome (FSFS) was suspected, and nutritional support was considered to have improved the skin condition. Key clinical message: This is the second reported case of presumed malnutrition-induced reversible FSFS and was accompanied by long-term follow-up.

Syndrome de fragilité cutanée réversible induit par la malnutrition soupçonné chez un chat avec des difformités axiales congénitales. Un chat errant, une femelle intacte de race japonaise à poil court et d'âge inconnu (suspecté être une jeune adulte), a été secourue. La chatte était léthargique et maigre, et avait une fragilité marquée de la peau, un retard dans la guérison de plaies sans hyperextensibilité de la peau, et une ataxie proprioceptive et parésie des membres postérieurs. Des radiographies, un examen par tomodensitométrie, et de l'imagerie par résonnance magnétique ont révélé des anomalies congénitales des vertèbres, incluant des vertèbres transitionnelles thoraco-lombaires, une scoliose résultant d'une vertèbre thoracique en forme de coin, une queue pliée, et un canal central de la moelle épinière dilaté. Grâce à un soutien nutritionnel, la condition générale du chat s'est stabilisée, suivi d'une amélioration graduelle et complète des caractéristiques de la peau. Le séquençage du génome complet a été effectué; toutefois, aucune variation génétique pathogénique n'a été identifiée qui aurait pu causer ce phénotype, incluant la scoliose congénitale. Une biopsie cutanée obtenue 7 j après le sauvetage n'a révélé aucune trouvaille spéciale à l'histopathologie ou par microscopie électronique à transmission. Basé sur le déroulement clinique et l'examen microscopique, le syndrome de fragilité cutanée réversible félin induit par la malnutrition (FSFS) était suspecté, et le soutien nutritionnel a été considéré comme ayant amélioré la condition cutanée.Message clinique clé :Ce cas est le deuxième cas rapporté de FSFS induit par la malnutrition soupçonné et a fait l'objet d'un suivi à long terme.(Traduit par Dr Serge Messier).

Investigation of the effect and availability of ketamine on electroencephalography in cats with temporal lobe epilepsy.

In recent years, electroencephalography (EEG) in veterinary medicine has become important not only in the diagnosis of epilepsy, but also in determining the epileptogenic focus. In cats, sedation and immobilization, usually with medetomidine or dexmedetomidine, are necessary to place the electrodes and to obtain stable scalp EEG recordings. In this study, we hypothesized that, for cats with temporal lobe epilepsy (TLE), ketamine, a sedative/anesthetic and N-methyl-D-aspartate (NMDA) antagonist that activates the limbic system and is also used to treat refractory status epilepticus in dogs, would induce sufficient sedation and immobilization for EEG, as well as induce interictal epileptiform discharges (IEDs) that are more pronounced than those induced with medetomidine. We obtained EEG recordings from TLE cats and healthy cats administered either ketamine or medetomidine alone (study 1) or ketamine after medetomidine sedation (study 2). In study 1, the frequency of IEDs showed no statistically significant difference between ketamine and medetomidine in both TLE and healthy cats. Seizures were observed in 75% (9/12) cats of the TLE group with ketamine alone. When ketamine was administered after sedation with medetomidine (study 2), 3/18 cats in the TLE group developed generalized tonic-clonic seizure and 1/18 cats showed subclinical seizure activity. However, no seizures were observed in all healthy cats in both study 1 and study 2. Slow wave activity at 2-4 Hz was observed in many individuals after ketamine administration regardless studies and groups, and quantitative analysis in study 2 showed a trend toward increased delta band activities in both groups. While there was no significant difference in the count of IEDs between medetomidine and ketamine, ketamine caused seizures in cats with TLE similar to their habitual seizure type and with a higher seizure frequency. Our results suggest that ketamine may activate epileptiform discharges during EEG recordings. However, caution should be used for cats with TLE.

Age-related brain atrophy in cats without apparent neurological and behavioral signs using voxel-based morphometry.

Introduction: Brain atrophy is observed with aging and may cause cognitive decline or dysfunction. Aging cats may demonstrate behavioral changes related to cognitive dysfunction. In the clinical veterinary field, although the conventional region of interest method by manual or semiauto tracing on magnetic resonance imaging is used to detect atrophy of regional structures, such as the hippocampus, it is difficult to assess atrophy globally. Voxel-based morphometry (VBM) has been developed to detect global and regional abnormalities in humans. The purpose of the present study investigates whether the feline brain volume decreases with aging using VBM analysis. Materials: A total of 65 cats, aged 17-200 months, without apparent neurological and behavioral signs were included in the statistical analysis. Results: We observed that the gray matter in the bilateral parietal lobes was decreased significantly with aging. The regions that showed decreased volume included the right postcruciate, cingulate gyrus, rostral suprasylvian/ectosylvian gyri, and the left postcruciate gyrus. No significant reduction in white matter was observed. Together, our results show that age-related brain atrophy can be detected using VBM analysis. Discussion: The age-related atrophy of the parietal cortex may not cause neurological and behavioral signs in cats. Therefore, veterinarians should consider age when assessing the relation between morphometric and functional abnormalities of the parietal cortex in cats.

Questionnaire survey on the usage of antiseizure drugs for dogs and cats in Japanese veterinary hospitals (2020).

Epilepsy is the most common neurological disorder in veterinary medicine. Recently, evidence-based recommendations or systematic reviews for using antiseizure drugs (ASDs) in dogs and cats have been published, but there are many differences in economic, geographical, and historical backgrounds and/or the availability of each ASD between countries. In the present study, we conducted a questionnaire survey on the usage of ASDs in 511 veterinary hospitals in Japan in 2020. As a result, zonisamide (ZNS) was the most commonly prescribed drug for idiopathic (83%) and structural epilepsy (76%) in dogs. In cats, phenobarbital was the most frequently prescribed drug for idiopathic (48%) and structural epilepsy (51%), but ZNS was also commonly prescribed (41% and 36%, respectively). Additionally, ZNS was the most frequently used ASD in combination therapy for canine idiopathic epilepsy. We also surveyed the frequency of measuring ASD blood levels; however, a relatively high percentage of hospitals (22%) did not perform such measurements. Although the evidence level for ZNS is still poor for both species, it is generally used as the first-line ASD in Japan. A large-scale and higher evidential study for ZNS and the education of practitioners for adequate antiseizure medication are required.

Corpus Callosotomy in 3 Cavalier King Charles Spaniel Dogs with Drug-Resistant Epilepsy.

Corpus callosotomy (CC) is an established palliative surgery for human patients with drug-resistant epilepsy (DRE), especially those with generalized seizures and multiple or unknown epileptogenic focus. However, there are no reports to describe CC in canine patients with epilepsy. Three client-owned Cavalier King Charles Spaniels with DRE are included in this case series. In presurgical evaluations, an apparent epileptogenic zone was not detected in each dog and CC was conducted. Total CC was performed in one dog, whereas the other two received partial CC. One dog recovered from surgery without any complications, but died suddenly by an unknown cause at 10 h after surgery. For the other two dogs, postoperative evaluations including seizure outcomes, complications, and quality of life of the dogs and owners were assessed for at least 12 months. Both dogs showed a remarkable decrease in seizure frequency (averaged 80.3% reduction) and severity after surgery. The antiseizure medications were maintained, and not only the mentation and activity of the dogs, but also the quality of life of dogs and owners were improved postoperatively. Although technical improvement and more large-scale studies are needed, CC is a treatment option for dogs with DRE in veterinary medicine.

Case Report: Corpus Callosotomy in a Cat With Drug-Resistant Epilepsy of Unknown Cause.

A 2-month-old, intact male domestic shorthair cat with dullness, bilateral central blindness, and recurrent epileptic seizures was presented to a local clinic. Seizures were the generalized myoclonic and tonic-clonic type. Phenobarbital was initiated and maintained; however, seizures were not controlled. Other anti-seizure drugs, including levetiracetam, zonisamide, and diazepam, also provided insufficient seizure control with seizures occurring hourly to daily. By 8 months of age, the cat displayed non-ambulatory tetraparesis and deep somnolence. Magnetic resonance imaging (MRI), cerebrospinal fluid analysis, and pre- and post-prandial total bile acid analyses were unremarkable. Scalp electroencephalography (EEG) revealed central dominant but generally synchronized spikes and multiple spikes. The cat was diagnosed with drug-resistant epilepsy of unknown cause and was included in a clinical trial of epilepsy surgery. Given the unremarkable MRI and bilateral synchronized EEG abnormalities, a corpus callosotomy was performed at 12 months of age, and partial desynchronization of spikes was confirmed on EEG. Incomplete transection was found in the genu of the corpus callosum on postoperative MRI. After surgery, the mental status and ambulation clearly improved, and seizure frequency and duration were remarkably reduced. Recheck with follow-up EEG and MRI were performed at 3, 6, and 12 months after surgery. Scores of activities of daily living and visual analog scales including cat's and owner's quality of life had also improved considerably. This case report is the first documentation of the one-year clinical outcome of corpus callosotomy in a clinical feline case with drug-resistant epilepsy.

Corrigendum: Focal Cortical Resection and Hippocampectomy in a Cat With Drug-Resistant Structural Epilepsy.

[This corrects the article DOI: 10.3389/fvets.2021.719455.].

Corrigendum: Focal Cortical Resection and Hippocampectomy in a Cat With Drug-Resistant Structural Epilepsy.

[This corrects the article DOI: 10.3389/fvets.2021.719455.].

Focal Cortical Resection and Hippocampectomy in a Cat With Drug-Resistant Structural Epilepsy.

Epilepsy surgery is a common therapeutic option in humans with drug-resistant epilepsy. However, there are few reports of intracranial epilepsy surgery for naturally occurring epilepsy in veterinary medicine. A 12-year-old neutered male domestic shorthair cat with presumed congenital cortical abnormalities (atrophy) in the right temporo-occipital cortex and hippocampus had been affected with epilepsy from 3 months of age. In addition to recurrent epileptic seizures, the cat exhibited cognitive dysfunction, bilateral blindness, and right forebrain signs. Seizures had been partially controlled (approximately 0.3-0.7 seizures per month) by phenobarbital, zonisamide, diazepam, and gabapentin until 10 years of age; however, they gradually became uncontrollable (approximately 2-3 seizures per month). In order to plan epilepsy surgery, presurgical evaluations including advanced structural magnetic resonance imaging and long-term intracranial video-electroencephalography monitoring were conducted to identify the epileptogenic zone. The epileptogenic zone was suspected in the right atrophied temporo-occipital cortex and hippocampus. Two-step surgery was planned, and a focal cortical resection of that area was performed initially. After the first surgery, seizures were not observed for 2 months, but they then recurred. The second surgery was performed to remove the right atrophic hippocampus and extended area of the right cortex, which showed spikes on intraoperative electrocorticography. After the second operation, although epileptogenic spikes remained in the contralateral occipital lobe, which was suspected as the second epileptogenic focus, seizure frequency decreased to <0.3 seizure per month under treatment with antiseizure drugs at 1.5 years after surgery. There were no apparent complications associated with either operation, although the original neurological signs were unchanged. This is the first exploratory study of intracranial epilepsy surgery for naturally occurring epilepsy, with modern electroclinical and imaging evidence, in veterinary medicine. Along with the spread of advanced diagnostic modalities and neurosurgical devices in veterinary medicine, epilepsy surgery may be an alternative treatment option for drug-resistant epilepsy in cats.

Ventrolateral temporal lobectomy in normal dogs as a counterpart to human anterior temporal lobectomy: a preliminary study on the surgical procedure and complications.

Anterior temporal lobectomy (ATL) is a surgical procedure for drug-resistant mesial temporal lobe epilepsy that is commonly performed in human medicine. The purpose of this study was to determine whether ATL-like surgery, i.e., removal of the amygdala and hippocampal head, is possible in dogs, and to investigate its safety and postoperative complications. Eight healthy beagles underwent ATL-like surgery and were observed for 3 months postoperatively. Samples from the surgically resected tissues and postmortem brain were evaluated pathologically. The surgical survival rate was 62.5%. The major postoperative complications were visual impairment, temporal muscle atrophy on the operative side, and a postoperative acute symptomatic seizure. Due to the anatomical differences between dogs and humans, the surgically resected area to approach the medial temporal structures in dogs was the ventrolateral part of the temporal lobe. Therefore, the ATL-like surgery described in this study was named "ventrolateral temporal lobectomy" (VTL). This study is the first report of temporal lobectomy including amygdalohippocampectomy in veterinary medicine and demonstrates its feasibility. Although it requires some degree of skill, VTL could be a treatment option for canine drug-resistant epilepsy and lesions in the mesial temporal lobe.

Magnetic Resonance Imaging and Histopathologic Findings From a Standard Poodle With Neonatal Encephalopathy With Seizures.

Neonatal encephalopathy with seizures (NEwS) is an epileptic encephalopathy with an autosomal recessive inheritance pattern found in Standard Poodle puppies. The causal genetic variant for NEwS has been identified as a homozygous missense mutation in ATF2 (c.152T>G, p.Met51Arg), and a pathological cerebellar change has been reported. Magnetic resonance imaging showed reduced whole-brain size, dilated ventricles, developmental abnormalities of the white matter of the cerebrum, white matter signal abnormalities in the occipital lobe, and abnormal morphology of the cerebellum. Histopathology included previously unrecognized irregular neuronal migration in the subventricular zone around the lateral ventricles in the frontal lobe and white matter rarefaction especially at the level of the occipital lobe in the cerebrum in addition to the cerebellar cortical dysplasia that has been previously described. The findings of this case may highlight the critical role of ATF2 in neurodevelopmental processes in the canine brain.

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.

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.