長谷川 大輔

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.

Objectives The objectives of this study were to establish a magnetic resonance imaging-based classification system for canine hyperadrenocorticism according to pituitary gland extension, determine indications for trans-sphenoidal hypophysectomy, and clarify the prognosis for each disease grade. Methods A 5-point classification system (Grades 1 to 5) was developed based on tumour extension in dorsal and cranio-caudal directions. Cases were then classified as Type A: no arterial circle of Willis or cavernous sinus involvement and Type B: cases in which these blood vessels were involved. Results Medical records and magnetic resonance imaging data of 37 cases with hyperadrenocorticism were reviewed. Thirty-three cases underwent surgery; 4 Grade 5 cases did not have appropriate indications for surgery, and other therapies were used. Complete resection was achieved for 3, 3, 22 and 1 Grade 1A, 2A, 3A and 3B cases, respectively. Resection was incomplete in 1, 1 and 2 Grade 3A, 3B and 4B cases, respectively. Remission was achieved in 29 cases. Recurrence occurred in 4 cases, all of which were classified as Grade 3. Clinical Significance Dogs with Type A, Grade 1 to 3 hyperadrenocorticism had a good prognosis following trans-sphenoidal hypophysectomy. Grade 3B, 4 and 5 cases may not be suitable for this surgery.

Background: GM1 and GM2 gangliosidoses are progressive neurodegenerative lysosomal storage diseases resulting from the excessive accumulation of GM1 and GM2 gangliosides in the lysosomes, respectively. The diagnosis of gangliosidosis is carried out based on comprehensive findings using various types of specimens for histological, ultrastructural, biochemical and genetic analyses. Therefore, the partial absence or lack of specimens might have resulted in many undiagnosed cases. The aim of the present study was to establish immunohistochemical and immunofluorescent techniques for the auxiliary diagnosis of canine and feline gangliosidoses, using paraffin-embedded brain specimens stored for a long period. Results: Using hematoxylin and eosin staining, cytoplasmic accumulation of pale to eosinophilic granular materials in swollen neurons was observed in animals previously diagnosed with GM1 or GM2 gangliosidosis. The immunohistochemical and immunofluorescent techniques developed in this study clearly demonstrated the accumulated material to be either GM1 or GM2 ganglioside. Conclusions: Immunohistochemical and immunofluorescent techniques using stored paraffin-embedded brain specimens are useful for the retrospective diagnosis of GM1 and GM2 gangliosidoses in dogs and cats.

A 12-year-old spayed female Labrador retriever was presented with forebrain signs. Brain MRI revealed a huge cystic lesion with the thickened falx in the frontal region. The brain parenchyma surrounding the lesion showed significant signs of a mass effect and also increased intracranial pressure. However, the dog suddenly became lucid after about two weeks, and an MRI scan one month after the initial study revealed a dramatically shrunken cystic lesion. The dog survived for over a year until it was euthanized for other reasons, and the brain lesion was diagnosed as a cystic meningioma histologically. To the authors' knowledge, this is the first report that described the reduction of the cystic lesion of a cystic meningioma in dogs.

Leucine-rich glioma-inactivated (LGI) protein was first thought to have a suppressor effect in the formation of some cancers. Developments in physiology and medicine made it possible to characterize the function of the LGI protein family and its crucial role in different conditions more precisely. These proteins play an important role in synaptic transmission, and dysfunction may cause hyperexcitability. Genetic mutation of LGI1 was confirmed to be the cause of autosomal dominant lateral temporal lobe epilepsy in humans. The LGI2 mutation was identified in benign familial juvenile epilepsy in Lagotto Romagnolo (LR) dogs. Cats with familial spontaneous temporal lobe epilepsy have been reported, and the etiology might be associated with LGI protein family dysfunction. In addition, an autoimmune reaction against LGI1 was detected in humans and cats with limbic encephalitis. These advances prompted a review of LGI protein function and its role in different seizure disorders.

Feline nasal tumours (NTs) are locally invasive and occasionally metastasise to distant sites. Although palliative hypofractionated radiotherapy (HRT) is used, its efficacy and long-term complications have not been adequately evaluated. The purpose of this study was to evaluate the efficacy of HRT in treating feline malignant NTs, including monitoring improvement in clinical signs, acute and late complications, and prognosis. The medical records of 65 cats with malignant NTs treated with HRT were included. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. The log-rank test and Cox proportional hazard model were used to evaluate factors that influenced OS and PFS. Clinical signs improved in 86.2% of cats following radiotherapy. Acute complications were observed in 58.5% of cats but were manageable and acceptable. Among late complications, cataract was most frequently observed (20.5%), and atrophy of the entire eyeball and osteochondroma at the irradiation site were each observed in two cats. The median OS and PFS in 65 cats were 432 days and 229 days, respectively. No significant difference between OS of cats with nasal lymphoma and that of cats with other tumours was observed. Despite some limitations due to the retrospective nature of the study, palliative HRT for feline NTs can be considered a useful treatment option because of the high incidence of improvement and more favourable prognosis, although it may be preferable not to use the hypofractionated regimen in young cats with lymphoma that are expected to survive for a long period. (C) 2014 Elsevier Ltd. All rights reserved.

A strain of familial spontaneous epileptic cats (FSECs) with typical limbic seizures was identified in 2010. The electroencephalographic features suggested that an epileptogenic zone is present in the mesial temporal structures (i.e., amygdala and/or hippocampus). In this study, visual evaluations and quantitative analyses were performed by using 3D MR hippocampal volumetry in comparing FSECs with age-matched controls. Visual hippocampal asymmetries were seen in 8 of 14 (57.1%) FSECs. The FSEC group showed a significantly higher asymmetric ratio (4.15%) than the control group (0.99%). The smaller side of hippocampal volume (HV) (0.206 cm(3)) in FSECs was significantly smaller than the mean HV in controls (0.227 cm(3)). However, the means of left and right HVs and total HVs in FSECs showed no differences because the laterality of hippocampal atrophy was different in each individual. Therefore, since FSECs represent a true model of spontaneous epilepsy, hippocampal volumetry should be evaluated in each individual as well as in human patients. The significant asymmetry of HV suggests the potential for hippocampal atrophy in FSECs. (C) 2014 Elsevier B.V. All rights reserved.

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 10-year-old spayed female Abyssinian cat was presented with cluster limbic focal seizures with secondary generalisation. From magnetic resonance imaging (MRI) findings, the cat was diagnosed clinically as having a glioma in the left piriform lobe, and hypofractionated radiation therapy (RT) was performed using a linear accelerator. Although the tumour size had reduced significantly at 4 months after RT, recurrence was observed at 11 months after RT. Additional RT was performed and was effective however, recurrence was observed at 11 months after the additional RT. Chemotherapy was started using nimustine (ACNU 30 mg/m2, every 6 weeks). Tumour regression was confirmed by follow-up MRIs from 2 to 5 months after starting chemotherapy. Four years and 2 months after the first presentation the cat died as a result of tumour lysis syndrome following treatment of a high-grade lymphoma. Histopathological diagnosis of the brain tumour confirmed anaplastic oligodendroglioma. © ISFM and AAFP 2013.

Several reports have described magnetic resonance (MR) findings in canine and feline lysosomal storage diseases such as gangliosidoses and neuronal ceroid lipofuscinosis. Although most of those studies described the signal intensities of white matter in the cerebrum, findings of the corpus callosum were not described in detail. A retrospective study was conducted on MR findings of the corpus callosum as well as the rostral commissure and the fornix in 18 cases of canine and feline lysosomal storage diseases. This included 6 Shiba Inu dogs and 2 domestic shorthair cats with GM1 gangliosidosis; 2 domestic shorthair cats, 2 familial toy poodles, and a golden retriever with GM2 gangliosidosis; and 2 border collies and 3 chihuahuas with neuronal ceroid lipofuscinoses, to determine whether changes of the corpus callosum is an imaging indicator of those diseases. The corpus callosum and the rostral commissure were difficult to recognize in all cases of juvenile-onset gangliosidoses (GM1 gangliosidosis in Shiba Inu dogs and domestic shorthair cats and GM2 gangliosidosis in domestic shorthair cats) and GM2 gangliosidosis in toy poodles with late juvenile-onset. In contrast, the corpus callosum and the rostral commissure were confirmed in cases of GM2 gangliosidosis in a golden retriever and canine neuronal ceroid lipofuscinoses with late juvenile-to early adult-onset, but were extremely thin. Abnormal findings of the corpus callosum on midline sagittal images may be a useful imaging indicator for suspecting lysosomal storage diseases, especially hypoplasia (underdevelopment) of the corpus callosum in juvenile-onset gangliosidoses.

A 9 year-old, neutered, male French Bulldog showing cluster seizures was diagnosed with a glioma in the right piriform cortex by MRI. Hypofractionated radiation therapy (RT) was performed using a linear accelerator. Although the lesion had involuted significantly at 2 months after RT, recurrence was observed at 4 months after RT. Chemotherapy was started using CCNU (60 mg/m(2) every 6-9 weeks) and was continued for one year. Follow-up MM revealed involution of the lesion and the intervals of CCNU were increased to every 9-14 weeks. Two years after the first presentation, the dog suffered status epilepticus, followed by deficits of left sided postural reaction with cognitive dysfunction. The dog died on day 910, and histopathological diagnosis confirmed anaplastic oligodenclroglioma.

犬の四肢軟部組織肉腫14症例に対して術後低分割放射線治療を行い、治療成績や放射線障害について回顧的研究を行った。再発率は7.1%、放射線障害は85.7%で何らかの障害が認められたが、現在まで重篤な障害は認められず、再発に対する影響もなかった。一、二および三年生存率はそれぞれ100、92.9および66.7%あった。また一、二および三年腫瘍コントロール率はそれぞれ85.7、71.4、57.1%であった。以上のことから、犬の四肢の軟部組織肉腫に対する術後低分割放射線治療は従来の根治目的の放射線治療スケジュールと比較して治療効果に大きな差はなく、麻酔のリスクや動物への負担、オーナーへの負担を軽減する上で有用な照射方法の1つと考えられた。

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.

Duchenne muscular dystrophy (DMID) is a devastating muscle disorder that is characterized by progressive muscle necrosis, fibrosis, and fatty infiltration. To examine the temporospatial pathological changes, a noninvasive evaluation method such as magnetic resonance imaging (MRI) is needed. The aim of this study was to precisely assess muscle necrosis and inflammation based on a sequence of T2-weighted imaging (T2WI), gadolinium-enhanced imaging, and selective fat suppression, chemical shift selective T2-weighted imaging (CHESS-T2WI), on a 3.0-Tesla MRI unit in 3-month-old and 7-year-old dogs with canine X-linked muscular dystrophy (CXMDJ), a suitable animal model for DMD. The results show that CHESS-T2WI was more sensitive and useful from the early to late stages of CXMDJ than T2WI or contrast enhancement imaging in the evaluation of muscle necrosis, because these latter sequences can be influenced by fatty infiltration or interstitial connective tissues. Muscle Nerve 40: 815-826, 2009

遺伝子型検査によってGM₁- ガングリオシドーシスと確定診断された3症例の柴犬において，臨床診断の過程で頭部MRIが撮像された． これらの症例のMRI検査を受けた月齢は異なっていたが（症例1 ：3カ月齢と7カ月齢，症例2 ：6カ月齢，症例3 ：8カ月齢），すべてに共通して，T2強調画像で大脳白質が左右対称性に高信号を呈し，灰白質と白質のコントラストが不明瞭であった． また，Fluid-attenuated inversion recovery画像でも同様の所見が認められた． このようなMRI所見が本疾患の特徴であると示唆されたため，頭部MRI検査は柴犬のGM₁- ガングリオシドーシスの補助的診断に有用であると考えられた． また，これら3症例の所在は近畿・中国地方であり，すべてに血統上の関連性が認められた．

Prior to euthanasia, brain magnetic resonance imaging (MRI) was performed for a five-year-old male Yorkshire Terrier following portosystemic shunt (PSS) surgical attenuation. Hyperintensity was observed on T1W images of the lentiform nuclei. Trace elements in this area were measured by inductively coupled plasma atomic emission spectrometry. The manganese concentration in the lentiform nuclei was four times higher than that in the control group. Therefore, the manganese accumulation would be the Substance that causes the hyperintensity on T1W images of the lentiform nuclei in PSS dogs.

With the eventual goal of making zonisamide (ZNS), a relatively new antiepileptic drug, available for the treatment of epilepsy in cats, the pharmacokinetics after a single oral administration at 10 mg/kg and the toxicity after 9-week daily administration of 20 mg/kg/day of ZNS were Studied in healthy cats. Pharmacokinetic parameters obtained with a single administration of ZNS at 10 mg/day were as follows: C(max) = 13.1 mu g/ml; T(max) = 4.0 h; T(1/2) = 33.0 h; areas under the curves (AUCs) - 720.3 mu g/ml h (values represent the medians). The Study with daily administrations revealed that the toxicity of ZNS was comparatively low in cats, suggesting that it may be an available drug for cats. However, half of the cats that were administered 20 mg/kg/day daily showed adverse reactions Such as anorexia, diarrhoea, vomiting, somnolence and locomotor ataxia. (C) 2008 ESFM and AAFP. published by Elsevier Ltd. All rights reserved.

A monoclonal antibody, K9BYU, was generated using Escherichia coli recombinant extracellular domain of canine neural cell adhesion molecule (N-CAM) as an antigen. Immunoreactivity of K9BYU to insect cell recombinant canine N-CAM was demonstrated by Western blotting using Sf9 insect cells transfected with the canine N-CAM gene, In Western blotting against canine brain tissue, K9BYU detected three isoforms of N-CAM that correspond to three major isoforms of human and mouse N-CAM (N-CAM-120, -140. and -180). From these results, K9BYU was considered to be a useful tool for research of canine N-CAM.

The posterior lobe of the pituitary gland (PL) normally shows characteristic high signal intensity (SI) on T1-weighted MR images (T1WI) in humans. The high S1 is thought to represent storage of arginine vasopressin (AVP) in the PL. Normal dogs also show a high SI on T1WIs, but the origin is unclear. In the present study, we investigated whether the high Sl in the PL on T1WIs in normal dogs is caused by AVP. We examined the Sl in the PL on T1WIs. plasma AVP concentrations and plasma osmolality in normal dogs after excessive AVP secretion was induced by hypertonic saline overload. In addition, functional changes in the supraoptic nucleus and paraventricular nucleus of the hypothalamus under AVP secretion-stimulated conditions were examined immunohistologically. Under hypertonic saline overload, plasma osmolality and plasma AVP concentrations gradually increased, while the Sl of the PL gradually decreased. This suggests that AVP secretion was stimulated by elevated osmolality. Moreover, there was a significant negative correlation between plasma AVP concentrations and the SI ratio of the PL. An immunohistochemical study of the hypothalamus nucleus revealed that AVP-immunopositive cells significantly increased in the hypertonic saline loaded dogs. We concluded that the high SI in the PL in TIWIs in normal dogs was caused by AVP stored at the site, and examination of the Sl in the PL using MRI is useful for diagnosis of abnormal pituitary glands.

We investigated the epidemiological characteristics of intervertebral disc herniation (IVDH) in Japan in a large population using a retrospective study. The sample population was dogs (n=297) with IVDH in Japan. Medical records were reviewed for breed, sex, age, affected interspace and neurological severity. The dogs were comprised of 132 cases of cervical IVDH (C-IVDH) and 165 cases of thoracolumbar IVDH (TL-IVDH). In Japan, the Dachshund, Beagle and Shih Tzu tended to suffer from both C-IVDH and TL-IVDH. The Shiba Inu, a characteristic Japanese dog breed, suffered from both C-IVDH and TL-IVDH, although there was little data relating to the whole breed. Male dogs tended to suffer from C-IVDH and TL-IVDH at a rate almost twice that of females in Japan. Among the three predominant dog breeds, the Dachshund, Beagle and Shih Tzu, the Dachshund tended to suffer from both C-IVDH and TL-IVDH at an earlier age than the Beagle, and the Beagle tended to Suffer from both C-IVDH and TL-IVDH earlier than the Shih Tzu. Among the three predominant breeds, the Shih Tzu, in particular, tended to suffer from both C-IVDH and TL-IVDH at multiple sites. Our data from Japan were in partial agreement with previous data from the U.S.A., and epidemiological characteristics of IVDH peculiar to Japan were also identified.

A male six-year-old Pomeranian showed recurrent seizures and progressive left hemiparesis. MRI revealed a mass in the right paramedian frontal-temporal region with hyperintensity on T1-weighted (T1W) and mixed-intensity on T2-weighted (T2W) images. After gadolinium enhancement, the mass was enhanced homogenously and demonstrated the dural tail sign. Surgical resection of mass was performed and its histological diagnosis was meningioma. The meningioma of this case had a high cellular density with some lipid contents and intra- and extra-tumor hemorrhage, however, calcification was not found. These cellular characteristics may contribute to a higher signal intensity on T1W imaging.

Magnetic resonance (MR) was conducted for an 8-year-old, intact male Spitz with sneezing, serous discharge and epistaxis from the left nasal cavity. MR imaging showed a nasal cavity-occupied mass of iso-intensity on T1WI, high-intensity on T2WI and markedly enhanced on contrast-enhanced T1WI at parts of rostal to medial ocular angle in the left cavity. After Surgery and intraoperative radiation, the mass was diagnosed intranasal hemangiosarcoma by histopathology. Although the dog showed the finding, which suggested recurrence after the treatment ending, about 30 months later, it maintained good conditions without evidence of metastasis.

This case report documents clinical and molecular findings in two littermate kittens of the Japanese domestic cat with GM2 gangliosidosis variant 0. Analysis included detailed physical, magnetic resonance imaging, biochemical, pathological and genetic examinations. At first, these littermate kittens showed typical cerebellar signs at approximately 2 months of age. About 2 months later, they progressively showed other neurological signs and subsequently died at about 7 months of age. Magnetic resonance imaging just before the death showed an enlarged ventricular system, T1 hyperintensity in the internal capsule, and T2 hyperintensity in the white matter of the whole brain. Histological findings suggested a type of lysosomal storage disease. Biochemical studies demonstrated that the kittens were affected with GM2 gangliosidosis variant 0, and a DNA assay finally demonstrated that these animals were homozygous for the mutation, which the authors had identified in a different family of the Japanese domestic cat. The findings in the present cases provide useful information about GM2 gangliosidosis variant 0 in Japanese domestic cats.

Magnetic resonance (MR) and computed tomography (CT) were performed in an 8-year-old, spayed female cat with chronic effort respiration at the inspiration phase and stertor. Increased bone opacity in the areas of the head, neck and thorax were observed on radiography. MR images showed no signal intensity on both transverse T1WI and T2WI of the nasal cavity. CT revealed increased bone density and hypertrophy of the nasal turbinate and a narrowed nasal passage. From these results, we concluded this case had osteopetrosis-like disease. and that the respiratory distress was caused by hypertrophy of the nasal turbinate.

FK-506 confers a neuroprotective effect and is thought to extend the time window for thrombolytic treatment of cerebral ischemia. These effects have not been assessed in an embolic stroke model. In addition, clinical studies have raised concern that FK-506 may increase the risk of hemorrhagic transformation by damaging vascular endothelial cells. We investigated whether combined administration of recombinant tissue plasminogen activator (rt-PA) and FK-S06 would extend the therapeutic time window without increasing the hemorrhagic transformation in a rat embolic stroke model. Male Sprague-Dawley rats (n=66) were subjected to embolic infarction and assigned into eight groups. Six of the groups were treated with or without FK-506 (0.3 mg/kg) administration at 60 min after embolization, together with and all six groups received systemic rt-PA administration (10 mg/kg) at 60, 90, or 120 min. Two permanent ischemia groups were administered saline either with or without FK-S06. Infarct and hemorrhagic volume were assessed at 24 h after embolization. Diffusion-weighted and perfusion-weighted magnetic resonance imaging (MRI) were performed in the groups administered rt-PA at 90 min and a vehicle control group to assess whether FK-S06 influenced the effectiveness of MRI in revealing ischemic lesion. FK-506 extended the therapeutic time window for systemic thrombolysis compared to rt-PA alone without increasing the risk for hemorrhage. Combined therapy with FK-506 salvaged some of the MRI, revealing ischemic lesions destined to infarction in the animals treated by rt-PA alone. Single low dose of FK-S06 alone did not ameliorate the embolic infarction, but it did prove effective in extending the therapeutic time windows for thrombolysis without increasing the risk of hemorrhagic transformation. (c) 2007 Elsevier B.V. All rights reserved.

The present study investigated cerebrospinal fluid (CSF) biomarkers for estimating degeneration of the central nervous system (CNS) in experimental dogs with GM1 gangliosidosis and preliminarily evaluated the efficacy of long-term glucocorticoid therapy for GM1 gangliosidosis using the biomarkers identified here. GM1 gangliosidosis, a lysosomal storage disease that affects the brain and multiple systemic organs, is due to an autosomal recessively inherited deficiency of acid beta-galactosidase activity. Pathogenesis of GM1 gangliosidosis may include neuronal apoptosis and abnormal axoplasmic transport and inflammatory response, which are perhaps consequent to massive neuronal storage of GM1 ganglioside. In the present study, we assessed some possible CSF biomarkers, such as GM1 ganglioside, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), neuronspecific enolase (NSE) and myelin basic protein (MBP). Periodic studies demonstrated that GM1 ganglioside concentration, activities of AST and LDH, and concentrations of NSE and MBP in CSF were significantly higher in dogs with GM1 gangliosidosis than those in control dogs, and their changes were well related with the months of age and clinical course. In conclusion, GM1 ganglioside, AST, LDH, NSE and MBP could be utilized as CSF biomarkers showing CNS degeneration in dogs with GM1 gangliosidosis to evaluate the efficacy of novel therapies proposed for this disease. In addition, we preliminarily treated an affected dog with long-term oral administration of pre'dnisolone and evaluated the efficacy of this therapeutic trial using CSF biomarkers determined in the present study. However, this treatment did not change either the clinical course or the CSF biomarkers of the affected dog, suggesting that glucocorticoid therapy would not be effective for treating GM1 gangliosidosis. (c) 2006 Elsevier B.V. All rights reserved.

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.

Animals with a portosystemic shunt (PSS) often have neurologic abnormalities. Diagnostic imaging, including brain magnetic resonance (MR) imaging, is not performed routinely in these animals. In this study, brain MR images were obtained in 13 dogs and three cats with a PSS, and in 15 dogs and five cats that were neurologically normal and used as controls. All animals with a PSS had widened sulci. In addition, 10 out of 13 dogs with a PSS and one out of three cats with a PSS had hyperintense focal areas in the lentiform nuclei on T1-weighted (T1W) images, which did not enhance after intravenous gadolinium. Following surgical correction of the PSS, MR imaging examinations were repeated in one dog and one cat. The hyperintensity of the lentiform nuclei had decreased. This study indicates that MR imaging findings of widened sulci and hyperintensity of the lentiform nuclei on T1W images may be found in dogs and cats with a PSS.

An imbalance of excitatory and inhibitory transmitters in the brain has been suggested to cause epileptic seizures. In this study, we investigated the kinetics of glutamate (GLU) and gamma-aminobutyric acid (GABA) in cerebrospinal fluid (CSF-GLU and CSF-GABA, respectively) using a high performance liquid chromatography (HPLC) in a canine model of complex partial status epilepticus (CPSE) induced by the microinjection of kainic acid (KA) into the unilateral amygdala. During the acute phase (3, 6, 12 and 48 hr after the onset of CPSE), CSF-GLU was significantly increased, while CSF-GABA was decreased, although not significantly. In the chronic phase, both CSF-GLU and CSF-GABA were significantly lower than normal at 72 hr after the onset of CPSE, and their levels returned to normal at 2 months. Results of the present study demonstrate that CSF-GLU is gradually increased in relation with seizure severity, and suggested the possibility that CSF-GABA was consistently decreased during CPSE induced by KA in dogs.

We evaluated the usefulness of MRI and compared it with CT for diagnosis of mesenteric lymphoma. in a dog. The results in the plain CT, dynamic CT and plain MR (T1WI and T2WI) images suggested that the mass was a large single nodular lesion with abundant blood perfusion. On enhanced MRI(T1WI), the mass was depicted as a tumor with adhesion to the gut wall. Exploratory laparotomy confirmed the mass was consistent with the findings on enhanced MRI. We think that MRI might be a useful imaging tool for diagnosis of canine mesenteric lymphoma.

Tracheal narrowing is described in two cats. In both cases, inspiratory radiographs demonstrated tracheal narrowing just cranial to the thoracic inlet; no narrowing was seen on expiratory radiographs. Magnetic resonance imaging revealed suspected nasal tumours in both cases, but no abnormalities were identified in the region of the narrowed trachea. Nasal biopsy confirmed intranasal lymphoma in one cat and nasal adenocarcinoma in the other. The former cat was treated with chemotherapy. The owner of the latter cat declined further treatment. The tracheal narrowing disappeared after the initiation of chemotherapy in the cat with intranasal lymphoma and it is suggested that the narrowing might have been associated with the nasal tumour. A careful evaluation of the airway, especially cranial to the narrowing, is recommended in cases of tracheal narrowing in cats.

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.

The prophylactic efficacy of desmopressin acetate (DDAVP) on diabetes insipidus (DI) after hypophysectomy was investigated in the dog. In the control group, hypernatremia with a plasma level of 155 mEq/l or higher persisted for 12 hr from the 4th to the 16th hour after hypophysectomy, and symptoms of DI developed within five days after surgery. In the DDAVP treatment group, these changes were not observed, showing that administration of DDAVP (4 mug, instillation, twice daily) effectively prevented hypernatremia that develops immediately after surgery and DI-like symptoms that persists for about one week after surgery.

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.

An intradural tumor in the upper cervical region was found in a dog with quadriparesis and chronic respiratory acidosis. Surgical removal of the tumor in the atlas and intraoperative radiotherapy were attempted. The tumor was histologically diagnosed as a neural glioma. A preoperative acid-base disturbance was dramatically improved after surgery. The clinical changes appeared in this case suggest that compression of the spinal cord at this region may cause paralysis of the respiratory muscles and secondarily result in chronic respiratory acidosis following the respiratory insufficiency.

A Shetland sheepdog with epilepsy refractory to antiepileptic drugs was brought to the division of Veterinary Radiology at Nippon Veterinary and Animal Science University. Scalp electroencephalography and computed tomography was performed, but no abnormality was detected in either examination. To obtain detailed information, electrodes were implanted on the dura mater, and the electrocorticogram (ECoG) was recorded. In the ECoG, sporadic spikes were detected in the left parietal region, suggesting the presence of the epileptic focus in this region. After the dog's death, abnormalities of gyri were found in the region where spikes were detected in the ECoG. On histopathological examination, laminar malacia of the cingulate gyrus was observed. Furthermore, in the hippocampus, neuronal loss of pyramidal cells was observed.