Approach to initial management of canine generalised epileptic seizures in primary-care veterinary practices in the United Kingdom.

OBJECTIVES: To investigate how primary care clinicians in the UK approach initial management of canine generalised epileptic seizures, including factors potentially associated with prescription and choice of anti-seizure drugs. MATERIALS AND METHODS: Electronic health records concerning 3,150,713 consultations (917,373 dogs) were collected from 224 veterinary practices by the Small Animal Veterinary Surveillance Network. Free-text clinical narratives were reviewed to identify those consistent with generalised epileptic seizure activity, including only those recording the first presentation for seizures. Dogs older than 6 years were excluded. RESULTS: Five hundred and seventeen cases were included. Sixty-seven dogs (13.0%) received anti-seizure drugs at first presentation; this was significantly more likely in dogs presented with cluster seizures (odds ratio 13.8, 95% confidence interval 7.3 to 26.1). Phenobarbital (n=36) and imepitoin (n=29) were the most frequently chosen anti-seizure drugs. Presentation for a single epileptic seizure occurred in 321 dogs; seven were prescribed anti-seizure drugs. Eighty-six dogs were presented with cluster seizures; 38 were prescribed anti-seizure drugs, most frequently imepitoin (n= 19) and phenobarbital (n=17). Of the dogs presenting with a single seizure and at least 6-month follow-up (n=165), 33 (20%) did not have subsequent seizures recorded. CLINICAL SIGNIFICANCE: Primary care clinicians rarely prescribed anti-seizure drugs following a single epileptic seizure in accordance with International Veterinary Epilepsy Task Force recommendations. Less than half of dogs initially presenting with cluster seizures were prescribed anti-seizure drugs. Imepitoin was frequently selected in the treatment of cluster seizures despite no authorisation for this purpose. These findings may ultimately contribute to improved cohesion in the management of canine epileptic seizures between primary care and referral institutions.

Late-onset Becker-type muscular dystrophy in a Border terrier dog.

A 9-year-old Border terrier was presented to a referral hospital after a 1-year history of progressive stiffness and exercise intolerance. Neurological examination was consistent with a neuromuscular disorder. Serum creatine kinase activity was mildly elevated. A myopathy was suspected based on MRI findings and electrophysiological examination. Muscle histopathology was consistent with a severe non-inflammatory myopathy of a dystrophic type. Immunofluorescence and western blotting confirmed a dystrophinopathy with an 80-kDa truncated dystrophin fragment similar to Becker muscular dystrophy in people. To our knowledge, this is the first description of a late-onset Becker-type muscular dystrophy in a dog, and the first description of a dystrophinopathy in a Border terrier. Muscular dystrophy in dogs should not be ruled out based on late onset clinical signs and only mildly elevated creatine kinase.

Characterization of Paroxysmal Gluten-Sensitive Dyskinesia in Border Terriers Using Serological Markers.

BACKGROUND: Paroxysmal gluten-sensitive dyskinesia (PGSD) in border terriers (BTs) results from an immunologic response directed against transglutaminase (TG)2 and gliadin. Recent evidence suggests that PGSD is only one aspect of a range of possible manifestations of gluten sensitivity in the breed. HYPOTHESIS/OBJECTIVES: Gluten sensitivity in BTs is a heterogeneous disease process with a diverse clinical spectrum; to characterize the phenotype of PGSD using TG2 and gliadin autoantibodies as diagnostic markers. ANIMALS: One hundred twenty-eight client-owned BTs with various disorders. METHODS: Prospective study. BTs with paroxysmal episodes and a normal interictal examination were phenotyped using footage of a representative episode and assigned to 3 groups: idiopathic epilepsy (IE), paroxysmal dyskinesia (PD), or other. Owners of each dog completed a questionnaire to obtain information regarding clinical signs. Healthy BTs formed a control group. Serum antibodies against TG2 and AGA were measured in all dogs. RESULTS: One hundred twenty-eight BTs were enrolled; 45 with PD, 28 with IE, 35 with other conditions, and 20 controls. Three overlapping phenotypes were identified; PD, signs suggestive of gastrointestinal disease, and dermatopathy. AGA-IgG concentrations were increased in PD, compared with IE (P = 0.012), controls (P < 0.0001) and other (P = 0.018) conditions. Anti-canine TG2-IgA concentrations were increased in PD, compared with IE (P < 0.0001), controls (P < 0.0001) and other (P = 0.012) conditions. Serological markers are highly specific for PGSD but lack sensitivity. CONCLUSIONS: PGSD appears part of a syndrome of gluten intolerance consisting of episodes of transient dyskinesia, signs suggestive of gastrointestinal disease, and dermatological hypersensitivity.

Classification of Involuntary Movements in Dogs: Myoclonus and Myotonia.

Myoclonus is a sudden brief, involuntary muscle jerk. Of all the movement disorders, myoclonus is the most difficult to encapsulate into any simple framework. On the one hand, a classification system is required that is clinically useful to aid in guiding diagnosis and treatment. On the other hand, there is need for a system that organizes current knowledge regarding biological mechanisms to guide scientific research. These 2 needs are distinct, making it challenging to develop a robust classification system suitable for all purposes. We attempt to classify myoclonus as "epileptic" and "nonepileptic" based on its association with epileptic seizures. Myotonia in people may be divided into 2 clinically and molecularly defined forms: (1) nondystrophic myotonias and (2) myotonic dystrophies. The former are a group of skeletal muscle channelopathies characterized by delayed skeletal muscle relaxation. Many distinct clinical phenotypes are recognized in people, the majority relating to mutations in skeletal muscle voltage-gated chloride (CLCN1) and sodium channel (SCN4A) genes. In dogs, myotonia is associated with mutations in CLCN1. The myotonic dystrophies are considered a multisystem clinical syndrome in people encompassing 2 clinically and molecularly defined forms designated myotonic dystrophy types 1 and 2. No mutation has been linked to veterinary muscular dystrophies. We detail veterinary examples of myotonia and attempt classification according to guidelines used in humans. This more precise categorization of myoclonus and myotonia aims to promote the search for molecular markers contributing to the phenotypic spectrum of disease. Our work aimed to assist recognition for these 2 enigmatic conditions.

Effect of a constant rate infusion of cytosine arabinoside on mortality in dogs with meningoencephalitis of unknown origin.

Administration of cytosine arabinoside (CA) by continuous rate infusion (CRI) has pharmacokinetic and pharmacodynamic advantages over traditional intermittent dosing. Whether these advantages translate into clinical efficacy remains unknown. The aim of this study was to assess the efficacy and safety of CRI of CA in dogs with meningoencephalitis of unknown origin (MUO) and to compare outcomes with a group of historical control dogs treated with conventional intermittent subcutaneous (SC) administration of CA; both groups received adjunctive prednisolone. It was hypothesised that a CRI of CA for 24 h at 100 mg/m(2) would improve survival and lesion resolution compared with conventional SC delivery of 50 mg/m(2) every 12 h for 48 h. Eighty dogs with suspected MUO were recruited from consecutive dogs presenting with suspected MUO from 2006 to 2015. All dogs underwent routine clinical evaluation, magnetic resonance imaging of the brain and cerebrospinal fluid analysis. There were 39 dogs in the SC group and 41 dogs in the CRI group; baseline characteristics were similar in both groups. Survival at 3 months was 22/39 (44%) with SC delivery versus 37/41 (90%) with CRI. No dose-limiting toxicities were noted for either group. The resolution rate of magnetic resonance imaging and cerebrospinal fluid abnormalities at the 3 month re-examination were substantially improved in the CRI group versus the SC group. The CRI regimen produced a survival advantage over the SC route of administration without clinically significant toxicity. These data supports the routine use of CRI at first presentation for the treatment of MUO in dogs.

Risk factors for early post-operative neurological deterioration in dogs undergoing a cervical dorsal laminectomy or hemilaminectomy: 100 cases (2002-2014).

Early post-operative neurological deterioration is a well-known complication following dorsal cervical laminectomies and hemilaminectomies in dogs. This study aimed to evaluate potential risk factors for early post-operative neurological deterioration following these surgical procedures. Medical records of 100 dogs that had undergone a cervical dorsal laminectomy or hemilaminectomy between 2002 and 2014 were assessed retrospectively. Assessed variables included signalment, bodyweight, duration of clinical signs, neurological status before surgery, diagnosis, surgical site, type and extent of surgery and duration of procedure. Outcome measures were neurological status immediately following surgery and duration of hospitalisation. Univariate statistical analysis was performed to identify variables to be included in a multivariate model. Diagnoses included osseous associated cervical spondylomyelopathy (OACSM; n = 41), acute intervertebral disk extrusion (IVDE; 31), meningioma (11), spinal arachnoid diverticulum (10) and vertebral arch anomalies (7). Overall 54% (95% CI 45.25-64.75) of dogs were neurologically worse 48 h post-operatively. Multivariate statistical analysis identified four factors significantly related to early post-operative neurological outcome. Diagnoses of OACSM or meningioma were considered the strongest variables to predict early post-operative neurological deterioration, followed by higher (more severely affected) neurological grade before surgery and longer surgery time. This information can aid in the management of expectations of clinical staff and owners with dogs undergoing these surgical procedures.

The Clinical and Serological Effect of a Gluten-Free Diet in Border Terriers with Epileptoid Cramping Syndrome.

BACKGROUND: Canine epileptoid cramping syndrome (CECS) is a paroxysmal movement disorder of Border Terriers (BTs). These dogs might respond to a gluten-free diet. OBJECTIVES: The objective of this study was to examine the clinical and serological effect of a gluten-free diet in BTs with CECS. ANIMALS: Six client-owned BTs with clinically confirmed CECS. METHODS: Dogs were prospectively recruited that had at least a 6-month history of CECS based on the observed phenomenology (using video) and had exhibited at least 2 separate episodes on different days. Dogs were tested for anti-transglutaminase 2 (TG2 IgA) and anti-gliadin (AGA IgG) antibodies in the serum at presentation, and 3, 6, and 9 months after the introduction of a gluten-free diet. Duodenal biopsies were performed in 1 dog. RESULTS: Serum TG2 IgA titers were increased in 6/6 BTs (P = .006) and AGA IgG titers were increased in 5/6 BTs at presentation compared to those of controls (P = .018). After 9 months, there was clinical and serological improvement in all BTs with CECS strictly adhering to a gluten-free diet (5/5). One dog had persistently increased antibody titers. This dog scavenged horse manure. On the strict introduction of a gluten-free diet this dog also had an improved clinical and serological response. The diet-associated improvement was reversible in 2 dogs on completion of the study, both of which suffered a relapse of CECS on the re-introduction of gluten. CONCLUSIONS: Canine epileptoid cramping syndrome in BTs is a gluten-sensitive movement disorder triggered and perpetuated by gluten and thus responsive to a gluten-free diet.

Acquired cervical spinal arachnoid diverticulum in a cat.

A one-year-old, female entire, domestic, shorthair cat presented with acute onset non-ambulatory tetraparesis. Magnetic resonance imaging was consistent with a C3-C4 acute non-compressive nucleus pulposus extrusion and the cat was treated conservatively. The cat was able to walk after 10 days and was normal 2 months after presentation. The cat was referred five and a half years later for investigation of an insidious onset 3-month history of ataxia and tetraparesis. Magnetic resonance imaging of the cervical spine was repeated, demonstrating a spinal arachnoid diverticulum at C3 causing marked focal compression of the spinal cord. This was treated surgically with hemilaminectomy and durectomy. The cat improved uneventfully and was discharged 12 days later.

Assessment of a tumor bank: a thirty years experience of the University of Siena (Italy).

Tumor biobank plays a pivotal role in cancer biomedical research. The collection of a high variety of biological samples, including DNA, RNA, tissues, cells, blood, plasma and other body fluids, represents a necessary step to plan new strategies in the improvement of oncological patient care. Since 1985, a consolidated experience in biobanking management has been developed at the University of Siena (Italy). During these years, some information about clinico-pathology, surgery and a high number of human bispecimens have been collected. Herein, we described our experience in sampling management to improve the cancer research and the patient care.

Corpus callosal abnormalities in dogs.

BACKGROUND: Corpus callosal abnormalities (CCA) in dogs have been only sporadically reported and are poorly characterized. HYPOTHESIS/OBJECTIVES: To describe the clinical presentation and magnetic resonance imaging (MRI) characteristics of dogs with CCA. ANIMALS: Fifteen client-owned dogs. METHODS: Retrospective study. Records of the contributing institutions were reviewed to identify dogs diagnosed with malformations affecting the corpus callosum (CC); cases in which the CCA was thought to be secondary were excluded. RESULTS: The most represented breeds were Staffordshire Bull Terriers (5/15) and Miniature Schnauzers (3/15; n = 3, 20%) and the mean age at time of presentation of 19 months (range 3-81 months). The clinical signs most commonly reported were adipsia/hypodipsia with associated hypernatremia (12/15), tremors (6/15), and seizures (6/15). Review of the MR images revealed that 10 dogs had absence of the rostral CC and hypoplasia of the caudal portion, 4 dogs had a diffusely hypoplastic and dysplastic CC, and 1 dog had a diffusely hypoplastic CC. In 14 cases, there was abnormal cortical development with fusion of the ventral frontal lobes and part of the diencephalon, indicating lobar holoprosencephaly. CONCLUSIONS AND CLINICAL IMPORTANCE: Previous literature has mainly associated CCA with adipsia and only 12 of 15 dogs in the current series demonstrated this abnormality. There are different degrees of the malformation but in 10 dogs the rostral portion of the CC is most severely affected. Fourteen dogs have simultaneous fusion of the midline structures rostral to the CC; this region has several structures involved in thirst regulation and might explain this derangement.

Phenotypic characterisation of canine epileptoid cramping syndrome in the Border terrier.

OBJECTIVES: To characterise the phenotype of Border terriers suspected to be affected by canine epileptoid cramping syndrome and to identify possible contributing factors. METHODS: Owners of Border terriers with suspected canine epileptoid cramping syndrome were invited to complete an online questionnaire. The results of these responses were collated and analysed. RESULTS: Twenty-nine Border terriers were included. Most affected dogs had their first episode before 3 years of age (range: 0·2 to 7·0 years). The majority of episodes lasted between 2 and 30 minutes (range: 0·5 to 150 minutes). The most frequent observations during the episodes were difficulty in walking (27 of 29), mild tremor (21 of 29) and dystonia (22 of 29). Episodes most frequently affected all four limbs (25 of 29) and the head and neck (21 of 29). Borborygmi were reported during episodes in 11 of 29 dogs. Episodes of vomiting and diarrhoea occurred in 14 of 29, with 50% of these being immediately before or after episodes of canine epileptoid cramping syndrome (7 of 14). Most owners (26 of 29) had changed their dog's diet, with approximately 50% (14 of 26) reporting a subsequent reduction in the frequency of episodes. CLINICAL SIGNIFICANCE: This study demonstrates similarities in the phenotype of canine epileptoid cramping syndrome to paroxysmal dystonic choreoathetosis, a paroxysmal dyskinesia reported in humans. This disorder appears to be associated with gastrointestinal signs in some dogs and appears at least partially responsive to dietary adjustments.

Meningoencephalitis of unknown origin: investigation of prognostic factors and outcome using a standard treatment protocol.

Meningoencephalitis of unknown origin (MUO) is a common inflammatory CNS disease in dogs, with a variable and unpredictable outcome. MRI and cerebrospinal fluid (CSF) features were prospectively evaluated to establish their utility as prognostic markers for predicting mortality, relapse and long-term outcome in 39 dogs with MUO. MRI and CSF analysis were performed at initial diagnosis and three months into treatment with prednisolone and cytosine arabinoside. When possible, MRI was repeated every 12 months thereafter. Median survival time was 26 days. All deaths occurred within 52 days of diagnosis (22/39; 56 per cent). One-third (13/39) died within 72 hours of diagnosis. Outcome was good or excellent in 12/17 surviving dogs. Loss of the cerebral sulci and foramen magnum herniation on MRI were associated with increased risk of mortality. An abnormal CSF analysis at the three-month re-examination was associated with increased risk of relapse (P=0.04). The combination of MRI and CSF analysis provided a greater sensitivity for predicting relapse than one modality alone. Discontinuing treatment before MRI lesions resolved always resulted in relapse. The presence of certain MRI characteristics may indicate an increased risk of mortality. Dogs alive three months following diagnosis have a very low risk of death due to MUO.

Cervical vertebral stenosis associated with a vertebral arch anomaly in the Basset Hound.

OBJECTIVES: To report the clinical presentation, imaging characteristics, treatment results, and histopathological findings of a previously undescribed vertebral malformation in the Basset Hound. ANIMALS AND METHODS: Retrospective case series study. Eighteen Basset Hounds presented for evaluation of a suspected cervical spinal cord problem. All dogs underwent computed tomography myelography or magnetic resonance imaging of the cervical region. RESULTS: Thirteen male and 5 female Basset Hounds between 6 months and 10.8 years of age (median: 1.4 years) were studied. Clinical signs varied from cervical hyperesthesia to nonambulatory tetraparesis. Imaging demonstrated a well-defined and smooth hypertrophy of the dorsal lamina and spinous process of ≥ 2 adjacent vertebrae. Although this bony abnormality could decrease the ventrodorsal vertebral canal diameter, dorsal midline spinal cord compression was predominantly caused by ligamentum flavum hypertrophy. The articulation between C4 and C5 was most commonly affected. Three dogs were lost to follow-up, 10 dogs underwent dorsal laminectomy, and medical management was initiated in 5 dogs. Surgery resulted in a good outcome with short hospitalization times (median: 4.5 days) in all dogs, whereas medical management produced more variable results. Histopathology confirmed ligamentum flavum hypertrophy and demonstrated the fibrocartilaginous nature of this anomaly. CONCLUSIONS AND CLINICAL IMPORTANCE: Dorsal lamina and spinous process hypertrophy leading to ligamentum flavum hypertrophy should be included in the differential diagnosis of Basset Hounds with cervical hyperesthesia or myelopathy. Prognosis after decompressive surgery is favorable. Although a genetic component is suspected, additional studies are needed to determine the specific etiology of this disorder.

Aetiology and long-term outcome of juvenile epilepsy in 136 dogs.

The aetiology and outcome of dogs with juvenile-onset seizures were investigated. One hundred and thirty-six dogs whose first seizure occurred before the age of one year were investigated. One hundred and two dogs were diagnosed with idiopathic epilepsy (IE), 23 with symptomatic epilepsy (SE), nine with reactive seizures (RS) and two with probable symptomatic epilepsy (pSE). The outcome was known in 114 dogs; 37 per cent died or were euthanased as a consequence of seizures. The mean survival time of this population of dogs was 7.1 years. Factors that were significantly associated with survival outcome included the diagnosis of SE and the number of antiepileptic drugs (AEDs) used before investigation. The use of one AED before investigation and a diagnosis of SE were associated with a negative outcome, whereas receiving no AED medications before referral was associated with a longer survival. For dogs with IE, survival time was shortened if the dog was a border collie or with a history of status epilepticus;receiving no AEDs before referral in the IE group was associated with a positive outcome. Seizure-free status was achieved in 22 per cent of dogs diagnosed with IE. While the survival times were longer than previously reported in canine epilepsy, similar remission rates to those reported in childhood epilepsy, where a 70 per cent remission rate is documented, were not seen in the canine juvenile population.

Porencephaly and hydranencephaly in six dogs.

A retrospective study was performed to identify dogs with cerebrospinal fluid-filled cavitatory lesions on MRI. Six dogs were included and the lesions were classified. In the three dogs in the present study with hydranencephaly, unilateral but complete loss of the temporal and parietal lobes was noted and had almost complete loss of the occipital and frontal lobes of a cerebral hemisphere. In the three dogs with porencephaly, there was unilateral incomplete loss of the parietal lobe and one dog had additional partial loss of the temporal and frontal lobes. Two of the dogs with porencephaly had seizures; the third showed no associated clinical signs. The dogs with hydranencephaly had mentation changes and circled compulsively. The two porencephalic dogs with seizures were treated with phenobarbitone. One of the dogs with hydranencephaly showed increased frequency and duration of circling; one dog's clinical signs did not progress and the third dog was euthanased due to increasing aggression. The dog with increased circling had ventriculoperitoneal shunt placement and the circling frequency reduced.

A novel movement disorder in related male Labrador Retrievers characterized by extreme generalized muscular stiffness.

OBJECTIVES: To describe the clinical phenotype of a new motor disorder in Labrador Retrievers. ANIMALS AND METHODS: Case series study. Seven young male Labrador Retrievers presented for evaluation of stiff gait. RESULTS: All affected dogs had generalized muscular stiffness, persistent at rest and resulting in restricted joint movements. They showed a forward flexed posture, festinating gait, and bradykinesia. Signs developed between 2 and 16 months of age and tended to stabilize in adulthood. Needle electromyogram in the conscious state showed continuous motor unit activity in resting epaxial and proximal limb muscles. This activity was abolished by general anesthesia. Muscle and nerve histopathology was normal. In 2 dogs necropsied, astrocytosis was evident throughout the spinal cord gray matter, reticular formation and caudate nuclei. Decreased neuronal counts were selectively found in the spinal cord Rexed's lamina VII, but not in VIII and IX. Pedigree analysis showed that the affected dogs were from 5 related litters. CONCLUSIONS AND CLINICAL IMPORTANCE: This new hypertonicity syndrome in Labrador Retrievers is unique because of the selective distribution of the histological lesions, the lack of progression in adulthood, and its exclusive occurrence in male dogs. Pedigree analysis suggests an X-linked hereditary disease, although other modes of inheritance cannot be ruled out with certainty. We hypothesize that altered output from basal nuclei and reticular formation together with motor neuron disinhibition caused by a decreased number of spinal cord interneurons leads to the muscular stiffness.