長谷川 大輔

BACKGROUND: Focal epileptic motor seizures manifested by limb contraction have been recognized anecdotally in Pomeranians. OBJECTIVES: To investigate clinical features of idiopathic epilepsy (IE) and epilepsy of unknown cause (EUC) in Pomeranians as well as the ADAM23 haplotype frequency previously reported as a common risk haplotype for epilepsy in several breeds of dogs. ANIMALS: Twenty-eight Pomeranians, including 15 with IE and 13 with EUC. Nine Pomeranians with epilepsy and 8 control Pomeranians were used for ADAM23 risk haplotype analysis. METHODS: Case series study including both retrospectively and prospectively collected cases. The ADAM23 haplotype was determined by direct sequencing of PCR amplicons. Data were analyzed descriptively. RESULTS: Focal epileptic seizures (FS) were the predominant type of seizure in 22 of 28 dogs (78.6%). Among these, 12 of the IE dogs (80.0%) and 10 of the EUC dogs (76.9%) showed FS. Notably, 21 of 22 Pomeranians with FS (95.5%) showed limb contraction during ictal periods. Some dogs with FS also showed immobility, generalized tremors, difficulty walking or moving, autonomic signs, orofacial automatisms or some combination during ictal events. Ten dogs with FS and limb contraction had electroencephalography (EEG) performed, and interictal epileptiform discharges were identified in 9 dogs. The haplotype frequency of ADAM23 in cases was lower (27.8%) than that of the controls (56.3%). CONCLUSIONS AND CLINICAL IMPORTANCE: In our study, FS was the predominant type of seizure in Pomeranians, and almost all cases with FS showed limb contraction, regardless of whether having IE or EUC.

Feline epilepsy is treated with antiseizure medications, which achieves fair to good seizure control. However, a small subset of feline patients with drug-resistant epilepsy requires alternative therapies. Furthermore, approximately 50 % of cats with epileptic seizures are diagnosed with structural epilepsy with or without hippocampal abnormality and may respond to surgical intervention. The presence of hippocampal pathology and intracranial tumors is a key point to consider for surgical treatment. This review describes feline epilepsy syndrome and epilepsy-related pathology, and discusses the indications for and availability of neurosurgery, including lesionectomy, temporal lobectomy with hippocampectomy, and corpus callosotomy, for cats with different epilepsy types.

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.

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.

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 female 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.

The use and availability of magnetic resonance imaging (MRI) and other neurosurgical devices is rapidly increasing in the field of veterinarian medicine. Coincident with these technological advances, there is an increased expectation to treat drug resistant epilepsy in dogs and cats by epilepsy surgery. However, the presurgical evaluation of epileptic animals, by using methodologies to detect the epileptogenic zone for example, have yet to become established in common practice. The epileptogenic zone, defined as the minimum amount of cortex to produce seizure freedom, consists of five conceptual cortical abnormal 'zones': symptomatogenic, irritative, seizure-onset, structurally abnormal (epileptogenic lesion) and functional deficit. These zones can now be detected by suitable modalities including ictal video monitoring, interictal non-invasive or invasive electroencephalography (EEG), ictal video-EEG, magnetoencephalography, structural and functional MRIs, or nuclear imaging. These diagnostic techniques are essential for selecting both appropriate patients and surgical techniques, and are also important in understanding the pathophysiology of epilepsy. This review describes the diagnostic techniques available for detecting each abnormal zone while considering the current veterinary status to realise future surgery for canine and feline epilepsy. (C) 2016 The Author. Published by Elsevier Ltd.

A feline strain of familial spontaneous epileptic cats (FSECs) with typical limbic seizures was identified in 2010, and have been maintained as a novel animal model of genetic epilepsy. In this study, we characterized the electroencephalographic (EEG) features of FSECs. On scalp EEG under sedation, FSECs showed sporadic, but comparatively frequent interictal discharges dominantly in the uni- or bilateral temporal region. Bemegride activation was performed in order to evaluate the predisposition of epileptogenicity of FSECs. The threshold doses of the first paroxysmal discharge, clinical myoclonus and generalized convulsion in FSECs were significantly lower than those in control cats. Chronic video-intracranial EEG monitoring revealed subclinical or clinical focal seizures with secondarily generalization onset from the unilateral amygdala and/or hippocampus. Clinical generalized seizures were also recorded, but we were unable to detect the onset site. The results of the present study show that FSECs resemble not only feline kindling or the kainic acid model and El mouse, but also human familial or sporadic mesial temporal lobe epilepsy. In addition, our results indicate that FSECs are a natural and valuable model of mesial temporal lobe epilepsy. (C) 2014 Elsevier B.V. All rights reserved.

A spontaneous epileptic model of cats has not been described previously. Recently, we identified familial epileptic cats and investigated their clinical features. These epileptic cats are healthy except for the presence of recurrent seizures that are typically a focal limbic seizure with secondary generalization. Furthermore, generalized seizures were induced by vestibular stimulation in some cats. This spontaneous epileptic cat strain may be a valuable model for idiopathic/genetic epilepsy. (C) 2010 Elsevier B.V. All rights reserved.

Hippocampal atrophy, which is a component of hippocampal sclerosis and recognized commonly in human intractable epilepsy, is controversial in canine epilepsy. We examined the hippocampal volume in 58 epileptic dogs and 35 control dogs using magnetic resonance (MR) images, and calculated the relative hippocampal volume asymmetry of the right and left hippocampus. Subjectively, there were visible MR imaging abnormalities in seven of the 58 epileptic dogs (12%). The hippocampel volume asymmetric ratio of epileptic dogs (5.84 +/- 4.47%) was significantly greater than that of control dogs (1.62 +/- 0.88%). Using a cutoff threshold asymmetric ratio of 6% that is indicated in human epilepsy, 28 epileptic dogs (48%) were characterized as having unilateral hippocampus atrophy. The hippocampal volume asymmetry ratio cannot be used to detect bilateral atrophy. In conclusion, although less frequent than that observed in human epilepsy patients, hippocampal atrophy may occur in canine epilepsy. (C) 2010 Veterinary Radiology & Ultrasound, Vol. 51, No. 5, 2010, pp 485-490.

The criteria for brain atrophy in dogs have not yet been established, because of wide variation in the morphology of the ventricles and sulci of the brain depending on the breed and size. In this study, we examined the thickness of the interthalamic adhesion in a transverse magnetic resonance image to investigate normal, to examine the correlation with age, body weight, and breed, and to assess whether measurement would be a useful indicator of brain atrophy. The animals used in this study were of various breeds and weight, and had no identifiable intracranial lesion. They were divided into two groups: a normal group (0.6-15-year-old, n = 66) and a demented aging group (12-18-year-old, n = 12). The interthalamic adhesion thickness in both T1- and T2-weighted transverse images were measured in all dogs. The interthalamic adhesion thickness in the normal and demented groups was 6.79 +/- 0.70 and 3.82 +/- 0.79 mm, respectively. The interthalamic adhesion thickness in the demented group was significantly smaller. In an analysis of the correlation of interthalamic adhesion thickness with age and weight in normal dogs, significant negative and positive correlation was recognized, respectively. However, the strength of these correlations was low. These results suggest that interthalamic adhesion thickness may be a good parameter for evaluating brain atrophy in dogs with cognitive dysfunction.

Objective: To investigate diffusion-weighted imaging (DWI) in status epilepticus, a canine model of kainic acid (KA)-induced complex partial status epilepticus (CPSE) was produced. In order to validate its usefulness, MR imaging was carried out at various times following onset of CPSE followed by histopathology. Material and methods: Six normal dogs were used in this study. In each dog, a cannula was stereotactically inserted into the left amygdala. One week after surgery, all dogs were imaged at MRI. Pre-injection imaging consisted of T2 weighted (T2W) imaging, fluid attenuated inversion recovery (FLAIR), and DWI. Two weeks after surgery, five dogs received intraamygdaloid KA microinjections. One dog was used as a control. MRI was carried out at 3, 6, 12, 24 and 48 h after onset of CPSE. Animals were euthanized immediately after MRI for histopathological evaluation. The average of each apparent diffusion coefficient (ADC) in the regions of interest was calculated from each DWI. Results: At 3 and 6 h, DWI hyperintensity and low ADC were found in the injected amygdala, without any T2W and FLAIR imaging changes. At 12 and 24 h, all imaging showed hyperintensity with higher ADC in the amygdala and the hippocampus. At 48 h, all imaging techniques showed continued hyperintensity, but ADC showed a trend towards normalization. This increasing hyperintensity in DWIs were in agreement with the degree of histopathology during CPSE. Summary: This study suggests that DWI is a useful imaging method for finding the epileptic focus or for examining potential epileptic brain damage in status epilepticus. (C) 2003 Elsevier B.V. All rights reserved.

Objective: In order to investigate kainic acid (KA)-induced amygdaloid seizure and seizure-induced brain damage in dogs, and to compare these findings with that in other species, a KA-induced seizure model in dogs was produced. Material and methods: Normal beagle dogs Were used. A Teflon cannula for KA injection was inserted into the left amygdala, and cortical or depth electrodes were positioned. One week after surgery, 1.5 mug of KA was microinjected into the left amygdala. EEGs and the behavior of the animals were monitored for 2 months after KA injection. In addition, neuron-specific enolase levels in the cerebrospinal fluid (CSF-NSE) were measured intermittently. At 2 months after the injection, histopathological studies were performed. Results: KA-treated dogs showed limbic seizures that started from the left amygdala within 30 min after injection. The seizures developed into complex partial status epilepticus (CPSE), and started independently from the bilateral amygdala during the CPSE. The CPSE lasted for 1-3 days, and the animals showed no spontaneous' seizures during the 2-month observation period. A significant increase in CSF-NSE was observed immediately after CPSE. Histopathologically, extensive necrosis, which formed large cavity lesions, was observed around the bilateral amygdala. Summary: A microinjection of KA into unilateral amygdala in dogs induced CPSE. The seizures elicited independently from bilateral amygdala, and bilateral limbic structures suffered extensive injury. In addition, CSF-NSE was demonstrated as a useful marker of acute neuronal damage. (C) 2002 Elsevier Science B.V. All rights reserved.