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.

Serum anti-GM2 and anti-GalNAc-GD1a IgG antibodies are biomarkers for acute canine polyradiculoneuritis.

OBJECTIVES: A previous single-country pilot study indicated serum anti-GM2 and anti-GA1 anti-glycolipid antibodies as potential biomarkers for acute canine polyradiculoneuritis. This study aims to validate these findings in a large geographically heterogenous cohort. MATERIALS AND METHODS: Sera from 175 dogs clinically diagnosed with acute canine polyradiculoneuritis, 112 dogs with other peripheral nerve, cranial nerve or neuromuscular disorders and 226 neurologically normal dogs were screened for anti-glycolipid antibodies against 11 common glycolipid targets to determine the immunoglobulin G anti-glycolipid antibodies with the highest combined sensitivity and specificity for acute canine polyradiculoneuritis. RESULTS: Anti-GM2 anti-glycolipid antibodies reached the highest combined sensitivity and specificity (sensitivity: 65.1%, 95% confidence interval 57.6 to 72.2%; specificity: 90.2%, 95% confidence interval 83.1 to 95.0%), followed by anti-GalNAc-GD1a anti-glycolipid antibodies (sensitivity: 61.7%, 95% confidence interval 54.1 to 68.9%; specificity: 89.3%, 95% confidence interval 82.0 to 94.3%) and these anti-glycolipid antibodies were frequently present concomitantly. Anti-GA1 anti-glycolipid antibodies were detected in both acute canine polyradiculoneuritis and control animals. Both for anti-GM2 and anti-GalNAc-GD1a anti-glycolipid antibodies, sex was found a significantly associated factor with a female to male odds ratio of 2.55 (1.27 to 5.31) and 3.00 (1.22 to 7.89), respectively. Anti-GalNAc-GD1a anti-glycolipid antibodies were more commonly observed in dogs unable to walk (OR 4.56, 1.56 to 14.87). CLINICAL SIGNIFICANCE: Anti-GM2 and anti-GalNAc-GD1a immunoglobulin G anti-glycolipid antibodies represent serum biomarkers for acute canine polyradiculoneuritis.

Single dose epidural methylprednisolone as a treatment and predictor of outcome following subsequent decompressive surgery in degenerative lumbosacral stenosis with foraminal stenosis.

Alternative treatments to surgery in canine degenerative lumbosacral stenosis (DLSS) remain limited and reliable predictors of outcome are lacking. The aims of this clinical trial were threefold: to assess the usefulness of single epidural steroid injection (ESI) in DLSS, to compare the outcomes of ESI and decompressive surgery, and evaluate ESI as a predictor of outcome following decompressive surgery. Dogs diagnosed with DLSS were prospectively recruited and administered an ESI. If clinical signs persisted or relapsed, decompressive surgery was recommended. Follow-up was obtained. Thirty-two dogs underwent ESI with 17 having subsequent surgery. Improvement after ESI was seen in 27/32 dogs (84.4%), with 17/22 (77.2%) relapsing within 6 months (n = 15/17 relapsing within 2 months). Five dogs failed to respond to ESI and another five (15.6%) presented a persistent post-ESI favourable response (mean follow-up time, 9.4 months). Post-surgical improvement occurred in all dogs. Outcome appeared more favourable following surgical decompression, with a trend towards reduced pain, increased mobility, and greater quality of life score. This study was unable to demonstrate that ESI could predict surgical outcome. ESI was confirmed as an effective treatment in most but not all cases, leading to transient alleviation of clinical signs for longer than previously reported. ESI provided a complete and apparently long-term sustained resolution of clinical signs in a subset of dogs. Despite this, there was indication that surgical decompression can lead to a more favourable outcome. Epidural steroid injection has a role in the management of DLSS dogs, particularly when surgery is not an option.

Congenital external hydrocephalus in a dog.

A 4-year-old female Chihuahua was presented with progressive seizures, blindness and lethargy. Neurolocalisation was consistent with a diffuse brain lesion affecting the forebrain and cerebellum. MRI demonstrated dilation of the subarachnoid space dorsolaterally surrounding the cerebrum, filled with cerebrospinal fluid (CSF). Ventricular system size was normal, but mild cerebral atrophy was suspected. There was pachymeningeal contrast enhancement, but CSF analysis was unremarkable. This lesion was interpreted to be an external hydrocephalus of suspected congenital origin.

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.

A presumptive case of gluten sensitivity in a border terrier: a multisystem disorder?

Paroxysmal gluten-sensitive dyskinesia (previously termed canine epileptoid cramping syndrome) is a condition of Border terriers in which the leading manifestation is neurological. The authors describe a case they believe to represent the first report of a Border terrier with a combination of neurological signs, atopy, positive serological results for anti-transglutaminase 2 (TG2 IgA) and anti-gliadin (AGA IgG) antibodies, and signs suggestive of gastrointestinal disease with pathological changes in the gastrointestinal tract-seemingly responsive to a gluten-free diet. As such, the authors suggest that gluten sensitivity in Border terriers may manifest as a multisystem disease in a similar manner to that seen in human beings.

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.

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.

Magnetic resonance imaging of the lentiform nuclei in dogs with portosystemic shunts.

OBJECTIVES: To develop and evaluate a method to quantify the T1-weighted magnetic resonance imaging signal intensity of the lentiform nuclei in dogs, and to determine if there is any significant difference in this signal intensity between dogs with portosystemic shunts and a control group. MATERIALS AND METHODS: A retrospective blinded study was performed to investigate the reliability and use of a quantitative method for assessing the T1-weighted magnetic resonance imaging signal intensity of the lentiform nuclei in dogs with and without portosystemic shunts. The lentiform nuclei index (mean lentiform nucleus signal intensity/mean white matter signal intensity) was calculated for nine dogs with portosystemic shunts and a control group of 14 dogs. RESULTS: The intra- and inter-observer intraclass correlation coefficients were considered excellent (>0 · 75), suggesting that the lentiform nuclei index is a reliable method. The dogs with portosystemic shunts had a higher lentiform nuclei index than the control group (P = 0 · 0127). CLINICAL SIGNIFICANCE: This method of quantifying the T1-weighted magnetic resonance imaging signal intensity of the lentiform nuclei was reliable and showed that dogs with portosystemic shunts tend to have increased signal intensity. Further prospective studies are necessary to investigate the clinical significance and applications of these findings.

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.

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.

Steroid responsive meningitis-arteritis: a prospective study of potential disease markers, prednisolone treatment, and long-term outcome in 20 dogs (2006-2008).

BACKGROUND: Previous multidrug studies have identified the value of prednisolone in treating steroid responsive meningitis-arteritis (SRMA) and the potential value of acute phase proteins (APPs) and immunoglobulin A (IgA) in diagnosis and monitoring. HYPOTHESIS: (1) Prednisolone monotherapy is a successful immunosuppressive modality in the treatment of SRMA; (2) protein markers are useful in identifying the potential for relapse. ANIMALS: Twenty client-owned dogs with SRMA presented to the University of Glasgow Small Animal Hospital between May 2006 and May 2008. METHODS: A prospective, observational study: CBC, biochemistry, and cerebrospinal fluid (CSF) analyses were performed. C-reactive protein (CRP), serum amyloid-A, alpha-1-acid glycoprotein, and haptoglobin (Hp) were assessed in the serum. IgA concentrations were determined in the serum and CSF. RESULTS: Clinical resolution of SRMA was achieved in all 20 dogs. Serum CRP concentration remained increased at remission in 16/20 dogs whereas CSF cytology was within normal limits in 20/20 dogs. Serum APPs decreased significantly on treatment (P<.05) except Hp, which remained unaltered. Serum and CSF IgA concentrations remained increased for the duration of treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: The prednisolone regimen presented was successful in treating SRMA without the need for additional drugs. Serum APPs are of use in the diagnosis and management of SRMA, particularly in relation to identifying relapse. Serum and CSF IgA concentrations remain increased throughout disease, aiding in diagnosis but not contributing to the management of SRMA.

The role of acute phase proteins in diagnosis and management of steroid-responsive meningitis arteritis in dogs.

Acute phase proteins (APPs) have become an important tool in the diagnosis, management and prognosis of inflammatory diseases in humans and are developing a similar utility in domestic species. Steroid-responsive meningitis arteritis (SRMA) is a well-recognised inflammatory disease of the dog, the diagnosis of which remains unsatisfactory based on clinical criteria and non-specific laboratory investigations. In this prospective pilot study the authors examined the acute phase response throughout the course of SRMA in serum and cerebrospinal fluid (CSF) by evaluating three key stages in disease management: presentation, treatment response and putative relapse. Serum APPs were found to be of value in supporting the diagnosis of SRMA and monitoring its treatment. C-reactive protein (CRP), serum amyloid-A (SAA), alpha-1-acid glycoprotein (AGP) and haptoglobin (Hp) all exhibited an increase above our laboratory reference range in nine patients at initial presentation. During treatment APPs decreased significantly compared to presentation except Hp which increased (Wilcoxon-Signed-Rank-test: CRP, SAA and AGP P<0.05). Serum CRP and SAA were also found to be of clinical value in the identification of putative relapse (seven cases), particularly in the light of unperturbed CSF parameters where APP concentrations were elevated. CSF APPs were found to be less reliable markers in the management of this disease. The results indicate that SRMA causes a significant APP response in dogs, which although not disease specific, is of value in supporting the diagnosis of SRMA.