Luisa De Risio

International veterinary epilepsy task force consensus report on epilepsy definition, classification and terminology in companion animals

Dogs with epilepsy are among the commonest neurological patients in veterinary practice and therefore have historically attracted much attention with regard to definitions, clinical approach and management. A number of classification proposals for canine epilepsy have been published during the years reflecting always in parts the current proposals coming from the human epilepsy organisation the International League Against Epilepsy (ILAE). It has however not been possible to gain agreed consensus, “a common language”, for the classification and terminology used between veterinary and human neurologists and neuroscientists, practitioners, neuropharmacologists and neuropathologists. This has led to an unfortunate situation where different veterinary publications and textbook chapters on epilepsy merely reflect individual author preferences with respect to terminology, which can be confusing to the readers and influence the definition and diagnosis of epilepsy in first line practice and research studies.In this document the International Veterinary Epilepsy Task Force (IVETF) discusses current understanding of canine epilepsy and presents our 2015 proposal for terminology and classification of epilepsy and epileptic seizures. We propose a classification system which reflects new thoughts from the human ILAE but also roots in former well accepted terminology. We think that this classification system can be used by all stakeholders.

Association of clinical and magnetic resonance imaging findings with outcome in dogs with presumptive acute noncompressive nucleus pulposus extrusion: 42 cases (2000–2007)

OBJECTIVE To assess associations of severity of neurologic signs (neurologic score), involvement of an intumescence, and findings of magnetic resonance imaging (MRI) with interval to recovery and outcome in dogs with presumptive acute noncompressive nucleus pulposus extrusions. DESIGN Retrospective case series. ANIMALS 42 dogs with presumptive acute noncompressive nucleus pulposus extrusions. PROCEDURES Medical records and magnetic resonance (MR) images of dogs evaluated from 2000 through 2007 were reviewed. Inclusion criteria were acute onset of nonprogressive myelopathy following trauma or strenuous exercise, MRI of the spine performed within 7 days after onset, MRI findings consistent with acute noncompressive nucleus pulposus extrusions, and complete medical records and follow-up. RESULTS Clinical neuroanatomic localization of lesions was to the C1-C5 (n = 6), C6-T2 (6), T3-L3 (28), and L4-S3 (2) spinal cord segments. Median neurologic score was 3.5. Median duration of follow-up was 804 days (range, 3 to 2,134 days) after onset of neurologic signs. Outcome was successful in 28 (67%) dogs and unsuccessful in 14 (33%) dogs. Severity of neurologic signs, extent of the intramedullary hyperintensity on sagittal and transverse T2-weighted MR images, and detection of intramedullary hypointensity on GRE images were all associated with outcome on univariate analysis. Results of multivariate analysis suggested that maximal cross-sectional area of the intramedullary hyperintensity on transverse T2-weighted MR images was the best predictor of outcome. CONCLUSIONS AND CLINICAL IMPORTANCE Clinical and MRI findings can help predict outcome in dogs with acute noncompressive nucleus pulposus extrusions.

Magnetic Resonance Imaging Findings and Clinical Associations in 52 Dogs with Suspected Ischemic Myelopathy

BACKGROUND The magnetic resonance imaging (MRI) features of ischemic myelopathy have been described in the human literature and in a small number of cases in the veterinary literature. HYPOTHESIS The aims of this study were to identify associations among MRI findings, timing of imaging, and presenting neurologic deficits in a large series of dogs with a presumptive diagnosis of ischemic myelopathy. ANIMALS AND METHODS The medical records and MR images of dogs with a presumptive diagnosis of ischemic myelopathy (2000-2006) were reviewed retrospectively. Inclusion criteria were acute onset of nonprogressive and nonpainful myelopathy, 1.5-tesla MRI of the spine performed within 7 days of onset, and complete medical records and follow-up information. Presumptive diagnosis was based on history, as well as clinical, MRI, and cerebrospinal fluid (CSF) findings. The extent of the lesion on MRI was assessed as the following: (1) the ratio between the length of the hyperintense area on sagittal T2-weighted images and the length of C6 or L2 vertebral body, and (2) the maximal cross-sectional area of the hyperintense area on transverse T2-weighted images as a percentage of cross-sectional area of the spinal cord. RESULTS Fifty-two dogs met the inclusion criteria. MRI findings were abnormal in 41 dogs and normal in 11 dogs. The presence of MRI abnormalities was not significantly associated with the timing of imaging (P = .3) but was associated with ambulatory status on presentation (P = .04). Severity of signs on presentation was associated with extent of the lesion on MRI (P = .02). CONCLUSION AND CLINICAL IMPORTANCE The severity of signs on presentation is associated with the presence and the extent of the lesion on MRI.

Fibrocartilaginous Embolic Myelopathy in Small Animals

Fibrocartilaginous embolic myelopathy (FCEM) typically results in peracute onset of nonpainful, nonprogressive (after the first 24 hours), and often asymmetric neurologic deficits. Definitive diagnosis can be reached only through histologic examination of the affected spinal cord segments. Although MRI is the preferred diagnostic imaging modality for the antemortem diagnosis of FCEM, it may not show any changes in the first 24 to 72 hours of disease. Severity of neurologic signs at initial examination and extent of the lesions seen on MRI can help predict outcomes in dogs with FCEM.

Missense Mutation in CAPN1 Is Associated with Spinocerebellar Ataxia in the Parson Russell Terrier Dog Breed

Spinocerebellar ataxia (SCA) in the Parson Russell Terrier (PRT) dog breed is a disease of progressive incoordination of gait and loss of balance. Clinical signs usually become notable between 6 and 12 months of age with affected dogs presenting with symmetric spinocerebellar ataxia particularly evident in the pelvic limbs. The degree of truncal ataxia, pelvic limb hypermetria and impaired balance is progressive, particularly during the initial months of disease. A certain degree of stabilisation as well as intermittent worsening may occur. At the later stages of the disease ambulation often becomes difficult, with owners often electing to euthanise affected dogs on welfare grounds. Using a GWAS approach and target-enriched massively-parallel sequencing, a strongly associated non-synonymous SNP in the CAPN1 gene, encoding the calcium dependent cysteine protease calpain1 (mu-calpain), was identified. The SNP is a missense mutation causing a cysteine to tyrosine substitution at residue 115 of the CAPN1 protein. Cysteine 115 is a highly conserved residue and forms a key part of a catalytic triad of amino acids that are crucial to the enzymatic activity of cysteine proteases. The CAPN1 gene shows high levels of expression in the brain and nervous system and roles for the protein in both neuronal necrosis and maintenance have been suggested. Given the functional implications and high level of conservation observed across species, the CAPN1 variant represents a provocative candidate for the cause of SCA in the PRT and a novel potential cause of ataxia in humans.

Genome-wide mRNA sequencing of a single canine cerebellar cortical degeneration case leads to the identification of a disease associated SPTBN2 mutation

BackgroundNeonatal cerebellar cortical degeneration is a neurodegenerative disease described in several canine breeds including the Beagle. Affected Beagles are unable to ambulate normally from the onset of walking and the main pathological findings include Purkinje cell loss with swollen dendritic processes. Previous reports suggest an autosomal recessive mode of inheritance. The development of massively parallel sequencing techniques has presented the opportunity to investigate individual clinical cases using genome-wide sequencing approaches. We used genome-wide mRNA sequencing (mRNA-seq) of cerebellum tissue from a single Beagle with neonatal cerebellar cortical degeneration as a method of candidate gene sequencing, with the aim of identifying the causal mutation.ResultsA four-week old Beagle dog presented with progressive signs of cerebellar ataxia and the owner elected euthanasia. Histopathology revealed findings consistent with cerebellar cortical degeneration. Genome-wide mRNA sequencing (mRNA-seq) of RNA from cerebellum tissue was used as a method of candidate gene sequencing. After analysis of the canine orthologues of human spinocerebellar ataxia associated genes, we identified a homozygous 8 bp deletion in the β-III spectrin gene, SPTBN2, associated with spinocerebellar type 5 in humans. Genotype analysis of the sire, dam, ten clinically unaffected siblings, and an affected sibling from a previous litter, showed the mutation to fully segregate with the disorder. Previous studies have shown that β-III spectrin is critical for Purkinje cell development, and the absence of this protein can lead to cell damage through excitotoxicity, consistent with the observed Purkinje cell loss, degeneration of dendritic processes and associated neurological dysfunction in this Beagle.ConclusionsAn 8 bp deletion in the SPTBN2 gene encoding β-III spectrin is associated with neonatal cerebellar cortical degeneration in Beagle dogs. This study shows that mRNA-seq is a feasible method of screening candidate genes for mutations associated with rare diseases when a suitable tissue resource is available.

International Veterinary Epilepsy Task Force consensus proposal: medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible.

Association of clinical and magnetic resonance imaging findings with outcome in dogs suspected to have ischemic myelopathy: 50 cases (2000-2006).

OBJECTIVE To determine whether clinical signs or magnetic resonance imaging findings were associated with outcome in dogs with presumptive ischemic myelopathy. DESIGN Retrospective case series. ANIMALS 50 dogs. PROCEDURES Medical records and magnetic resonance images were reviewed. A neurologic score from 1 (normal) to 5 (most severe degree of dysfunction) was assigned on the basis of neurologic signs at the time of initial examination. Follow-up information was obtained from the medical records and by means of a telephone questionnaire completed by owners and referring veterinarians. RESULTS Median neurologic score at the time of initial examination was 3 (range, 2 to 5). Median follow-up time was 584 days (range, 4 to 2,090 days). Neurologic score at the time of initial examination and extent of the lesion seen on magnetic resonance images (quantified as the lesion length-to-vertebral length ratio and as the percentage cross-sectional area of the lesion) were significantly associated with outcome. Sensitivity of using a lesion length-to-vertebral length ratio > 2.0 or a percentage cross-sectional area of the lesion > or = 67% to predict an unsuccessful outcome was 100%. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that severity of neurologic signs at the time of initial examination and extent of the lesions seen on magnetic resonance images were associated with outcome in dogs with ischemic myelopathy.

Changes over time in craniocerebral morphology and syringomyelia in cavalier King Charles spaniels with Chiari-like malformation.

BackgroundChiari-like malformation (CM) and syringomyelia is a neurological disease complex with high prevalence in cavalier King Charles spaniels (CKCS). The natural progression of this disease with time has not been described. The objectives of this study were to i) determine if syringomyelia progresses with time ii) determine if features of craniocrebral morphology previously associated with CM are progressive (including caudal cranial fossa volume, caudal cranial fossa parenchymal volume, ventricular dimensions, height of the foramen magnum and degree of cerebellar herniation). A retrospective morphometric analysis was undertaken in 12 CKCS with CM for which repeat magnetic resonance images were available without surgical intervention.ResultsThe maximal syrinx width, height of the foramen magnum, length of cerebellar herniation and caudal cranial fossa volume increased over time. Ventricular and caudal fossa parenchymal volumes were not significantly different between scans.ConclusionsThe results of this study suggest that syringomyelia progresses with time. Increased caudal cranial fossa volume may be associated with active resorption of the supraoccipital bone, which has previously been found in histology specimens from adult CKCS. We hypothesise that active resorption of the supraoccipital bone occurs due to pressure from the cerebellum. These findings have important implications for our understanding of the pathogenesis and variable natural clinical progression of CM and syringomyelia in CKCS.

Surgical Technique, Postoperative Complications and Outcome in 14 Dogs Treated for Hydrocephalus by Ventriculoperitoneal Shunting

OBJECTIVE To report frequency and type of complications, and outcome in dogs with severe neurologic signs secondary to internal, suspected obstructive hydrocephalus treated by ventriculoperitoneal (VP) shunting. STUDY DESIGN Case series. ANIMALS Dogs (n=14). METHODS Medical records (2001-2006) was reviewed for dogs that had VP shunting. Inclusion criteria were complete medical record, progressive forebrain signs unresponsive to medical treatment, normal metabolic profile, negative antibody titers and/or cerebrospinal PCR for Toxoplasma gondii, Neospora caninum, and canine distemper virus, magnetic resonance images of the brain, confirmed diagnosis of VP shunting, and follow-up information. RESULTS Hydrocephalus was idiopathic in 5 dogs and acquired (interventricular tumors, intraventricular hemorrhage, inflammatory disease) in 9 dogs. Four dogs developed complications 1 week to 18 months postoperatively, including ventricular catheter migration, infection, shunt under-drainage, kinking of the peritoneal catheter, valve fracture, and abdominal skin necrosis. Three of these dogs had 1 or more successful revision surgeries and 1 dog was successfully treated with antibiotics. All, but 1 dog, were discharged within 1 week of surgery, and had substantial neurologic improvement. Median survival time for all dogs was 320 days (1-2340 days), for dogs with idiopathic hydrocephalus, 274 (60-420) days and for dogs with secondary hydrocephalus, 365 (1-2340) days. CONCLUSIONS VP shunting was successful in relieving neurologic signs in most dogs and postoperative complications occurred in 29%, but were resolved medically or surgically.