Untersuchung zum Vorkommen idiopathischer Epilepsie beim Border Collie

Idiopathic epilepsy (IE) is a common breed-related neurological disorder in contemporary small animal medicine. The number of Border Collies (BCs) with epileptic seizures is increasing while there is a lack of data of IE in this breed. Hypothesis of this study was that IE occurs in BCs and manifests often with severe clinical signs and poor response to medical treatment. IE was diagnosed by recurrent seizures, normal physical, neurological and laboratory examination. MRI and CSF analysis were requested if age at seizure onset was 5 years of age. Dogs that failed to meet all inclusion criteria were only considered if a first- or second-degree relative was afflicted by IE or if seizures had occurred for at least 2 years without interictal neurological abnormalities. Owners fulfilled a detailed questionnaire. Subsequent phenotypic case classification was performed by evaluation of seizure history and treatment data. Pedigrees were sampled and matched for the appearance of common ancestors. Ninety BCs with a reported seizure history were collected retrospectively and prospectively. Forty-nine of them were diagnosed with IE and were included in the present study. Clinical manifestations were dominated by moderate (33 %) and severe clinical courses (49 %) defined by the occurrence of cluster seizures or status epilepticus, respectively. Pharmacoresistance was apparent in 71 % of 24 dogs treated with ≥ 2 antiepileptic drugs. So far, no predictors for the occurrence of pharmacoresistance were identified in the present study. The epilepsy remission rate was 18 %. Dogs in remission showed a significantly higher median age at onset and a significantly lower initial seizure frequency compared to dogs with active epilepsy (p < 0.05). Survival time was significantly reduced in dogs aged < 2 years at seizure onset and in dogs with severe clinical courses (p < 0.05). Family- and pedigree analyses indicated a strong genetic founder effect in the appearance of epilepsy, resembling autosomal recessive inheritance. Yet, complex inheritance could not be excluded. In conclusion, IE occurs in BCs and is frequently associated with severe clinical signs and pharmacoresistance. While further genetic research is required, the results of this study suggest a substantial hereditary (disease) component

Traumatic odontoid process synchondrosis fracture with atlantoaxial instability in a calf: clinical presentation and imaging findings

A 6-week-old female Simmental calf was evaluated for acute non-ambulatory tetraparesis. Physical and laboratory examinations revealed no clinically relevant abnormalities. Neurological findings were consistent with acute, progressive and painful cervical myelopathy. Radiographs displayed a fractured odontoid process (dens axis) and vertebral step misalignment at the fracture site. A traumatic origin was suspected. Advanced diagnostic imaging was considered to allow better planning of potential surgical stabilisation and to exclude any additional lesions of the cervical vertebral column. However, during trailer transportation to the advanced diagnostic imaging and surgery site, the calf deteriorated neurologically and was humanely euthanised. Magnetic resonance imaging (MRI) and computed tomography (CT) were performed immediately post-mortem for scientific reasons. The MRI examination reflected the radiographic findings and confirmed severe spinal cord compression at the fracture site. In addition, a T2W-hyperintense signal change within the paravertebral soft tissue dorsal to the fracture site was indicative of a traumatic event. CT identified the fracture site at the synchondrosis between the odontoid process and the body of the axis, and this finding was confirmed by post-mortem examination. Advanced diagnostic imaging and post-mortem examination did not identify any other cervical lesion. In summary, this calf was diagnosed with a traumatic odontoid process synchondrosis fracture, which has not been reported previously in calves but presents a challenging and well-known fracture type in young children. This case report indicates that the odontoid process synchondrosis is a potential predisposed injury site and that traumatic odontoid process synchondrosis fractures should be considered as a potential differential in calves with acute cervical pain and/or signs of a cervical myelopathy

Dual, HLA-B27 Subtype-dependent Conformation of a Self-peptide

The products of the human leukocyte antigen subtypes HLA-B*2705 and HLA-B*2709 differ only in residue 116 (Asp vs. His) within the peptide binding groove but are differentially associated with the autoimmune disease ankylosing spondylitis (AS); HLA-B*2705 occurs in AS-patients, whereas HLA-B*2709 does not. The subtypes also generate differential T cell repertoires as exemplified by distinct T cell responses against the self-peptide pVIPR (RRKWRRWHL). The crystal structures described here show that pVIPR binds in an unprecedented dual conformation only to HLA-B*2705 molecules. In one binding mode, peptide pArg5 forms a salt bridge to Asp116, connected with drastically different interactions between peptide and heavy chain, contrasting with the second, conventional conformation, which is exclusively found in the case of B*2709. These subtype-dependent differences in pVIPR binding link the emergence of dissimilar T cell repertoires in individuals with HLA-B*2705 or HLA-B*2709 to the buried Asp116/His116 polymorphism and provide novel insights into peptide presentation by major histocompatibility antigens

Allele-Dependent Similarity between Viral and Self-Peptide Presentation by Hla-B27 Subtypes

Molecular mimicry is discussed as a possible mechanism that may contribute to the development of autoimmune diseases. It could also be involved in the differential association of the human major histocompatibility subtypes HLA-B(*)2705 and HLA-B(*)2709 with ankylosing spondylitis. These two subtypes differ only in residue 116 of the heavy chain (Asp in B(*)2705 and His in B(*)2709), but the reason for the differential disease association is not understood. Using x-ray crystallography, we show here that the viral peptide pLMP2 (RRRWRRLTV, derived from latent membrane protein 2 (residues 236-244) of Epstein-Barr virus) is presented by the B(*)2705 and B(*)2709 molecules in two drastically deviating conformations. Extensive structural similarity between pLMP2 and the self-peptide pVIPR (RRKWRRWHL, derived from vasoactive intestinal peptide type 1 receptor (residues 400-408)) is observed only when the peptides are presented by B(*)2705 because of a salt bridge between Arg(5) of both peptides and the subtype-specific heavy chain residue Asp(116). Combined with functional studies using pLMP2/pVIPR-cross-reactive cytotoxic T cell lines and clones, together with target cells presenting these peptides or a modified peptide analogue, our results reveal that a pathogen-derived peptide can exhibit major histocompatibility complex class I subtype-dependent, drastically distinct binding modes. Furthermore, the results demonstrate that molecular mimicry between pLMP2 and pVIPR in the HLA-B27 context is an allele-dependent property

Effect of different rates of quercetin and rutin on the biology of Anticarsia gemmatalis

Durante os anos de 1994 e 1995, foram realizados três ensaios de laboratório, na Embrapa-Centro Nacional de Pesquisa de Soja, em Londrina, PR, com o objetivo de avaliar o efeito de diferentes doses de rutina e de quercetina - compostos fenólicos (flavonóides) encontrados em folhas jovens dos genótipos de soja PI 227687 e 229358, resistentes a insetos -, na biologia da lagarta-da-soja, Anticarsia gemmatalis Hübner, 1818 (Lepidoptera, Noctuidae). Cada flavonóide foi incorporado, em diferentes concentrações, na dieta artificial do inseto, sendo um experimento conduzido com adição de rutina, e dois, com adição de quercetina. Tanto a quercetina quanto a rutina causaram aumento do número de dias de duração do terceiro ao sexto ínstar, do ciclo total (terceiro ínstar até fase adulta) e aumento da taxa de mortalidade de lagartas, de forma crescente, de acordo com o acréscimo das doses incorporadas à dieta artificial. Com a adição de quercetina, foi observada mortalidade de pupas e redução do peso de pupas em um dos experimentos, porém a duração da fase não foi alterada pelos tratamentos. Os resultados indicaram que os efeitos dos flavonóides sobre os insetos se manifestam a partir do terceiro ou quarto ínstar, porém são mais intensos no quinto e sexto ínstar.Along the years of 1994 and 1995, three laboratory experiments were set up at Embrapa-Centro Nacional de Pesquisa de Soja, in Londrina, PR, Brazil, aiming to evaluate the effect of different rates of rutin and quercetin, phenolic compounds (flavonols) found in young leaves of the resistant soybean genotypes PI 227687 and 229358, on the biology of the velvetbean caterpillar, Anticarsia gemmatalis Hübner, 1818 (Lepidoptera, Noctuidae). Each flavonol was incorporated in the diet, in diferent rates; one experiment was set up incorporating rutin and two incorporating quercetin. Both quercetin and rutin lead to an increase on the duration of larval instars, and from 3rd instar to adult emergence, as well as to increased mortality of larvae, being the effects related to the increasing incorporated rates. Addition of quercetin to the diet caused pupal mortality and also pupal weight reduction in one of the tests, but the duration of this stage was not affected by treatments. Results indicated that effects of the flavonols on the insects begin on the 3rd or 4th instar, but they are more evident during the 5th and 6th instars

Generalized myoclonic epilepsy with photosensitivity in juvenile dogs caused by a defective DIRAS family GTPase 1

The clinical and electroencephalographic features of a canine generalized myoclonic epilepsy with photosensitivity and onset in young Rhodesian Ridgeback dogs (6 wk to 18 mo) are described. A fully penetrant recessive 4-bp deletion was identified in the DIRAS family GTPase 1 (DIRAS1) gene with an altered expression pattern of DIRAS1 protein in the affected brain. This neuronal DIRAS1 gene with a proposed role in cholinergic transmission provides not only a candidate for human myoclonic epilepsy but also insights into the disease etiology, while establishing a spontaneous model for future intervention studies and functional characterization

Risk factors for cluster seizures in canine idiopathic epilepsy

Cluster seizures (CS), two or more seizures within a 24-hour period, are reported in 38–77% of dogs with idiopathic epilepsy (IE). Negative outcomes associated with CS include a reduced likelihood of achieving seizure freedom, decreased survival time and increased likelihood of euthanasia. Previous studies have found factors including breed, sex and neuter status are associated with CS in dogs with IE; however, only one UK study in a multi-breed study of CS in IE patients exists to the author's knowledge, and thus further data is required to confirm these results. Data from 384 dogs treated at a multi-breed canine specific epilepsy clinic were retrospectively collected from electronic patient records. 384 dogs were included in the study, of which nearly half had a history of CS (49.1%). Dogs with a history of CS had a younger age at onset than those without (p = 0.033). In a multivariate model, three variables predicted risk of CS: a history of status epilepticus (p = 0.047), age at seizure onset (p = 0.066) and breed (German Shepherd Dog) (p < 0.001). Dogs with a history of status epilepticus and dogs with an older age at seizure onset were less likely to be affected by cluster seizures. German Shepherd Dogs (71% experiencing CS) were significantly more likely to suffer from CS compared to Labrador Retrievers (25%) (p < 0.001). There was no association between sex, neuter status, body size and CS. Further studies into the pathophysiology and genetics of CS are required to further understand this phenomenon

International Veterinary Epilepsy Task Force Consensus Proposal: Diagnostic approach to epilepsy in dogs

This article outlines the consensus proposal on diagnosis of epilepsy in dogs by the International Veterinary Epilepsy Task Force. The aim of this consensus proposal is to improve consistency in the diagnosis of epilepsy in the clinical and research settings. The diagnostic approach to the patient presenting with a history of suspected epileptic seizures incorporates two fundamental steps: to establish if the events the animal is demonstrating truly represent epileptic seizures and if so, to identify their underlying cause. Differentiation of epileptic seizures from other non-epileptic episodic paroxysmal events can be challenging. Criteria that can be used to make this differentiation are presented in detail and discussed. Criteria for the diagnosis of idiopathic epilepsy (IE) are described in a three-tier system. Tier I confidence level for the diagnosis of IE is based on a history of two or more unprovoked epileptic seizures occurring at least 24 h apart, age at epileptic seizure onset of between six months and six years, unremarkable inter-ictal physical and neurological examination, and no significant abnormalities on minimum data base blood tests and urinalysis. Tier II confidence level for the diagnosis of IE is based on the factors listed in tier I and unremarkable fasting and post-prandial bile acids, magnetic resonance imaging (MRI) of the brain (based on an epilepsy-specific brain MRI protocol) and cerebrospinal fluid (CSF) analysis. Tier III confidence level for the diagnosis of IE is based on the factors listed in tier I and II and identification of electroencephalographic abnormalities characteristic for seizure disorders. The authors recommend performing MRI of the brain and routine CSF analysis, after exclusion of reactive seizures, in dogs with age at epileptic seizure onset 6 years, inter-ictal neurological abnormalities consistent with intracranial neurolocalisation, status epilepticus or cluster seizure at epileptic seizure onset, or a previous presumptive diagnosis of IE and drug-resistance with a single antiepileptic drug titrated to the highest tolerable dose