Thoracolumbar hydrated nucleus pulposus extrusion and intervertebral disc extrusion in dogs: Comparison of clinical presentation and magnetic resonance imaging findings.

Thoracolumbar hydrated nucleus pulposus extrusion (TL-HNPE) is an increasingly recognised pathology with a substantial lack of literature describing its features. The aim of this retrospective case-control study was to analyse the clinical and magnetic resonance imaging (MRI) features of dogs with TL-HNPE compared to dogs affected with thoracolumbar intervertebral disc extrusion (TL-IVDE). Data from dogs diagnosed with TL-HNPE and TL-IVDE via MRI at two referral hospitals, were retrospectively collected and compared in terms of clinical signs and MRI features. Cases diagnosed with TL-IVDE were deemed controls. The MRI features of the affected IVD space, herniated IVD material, affected overlying spinal cord and local epaxial musculature were evaluated for each group. Fifty-one cases with TL-HNPE and 105 randomly selected cases of TL-IVDE were included. Several signalment and neurological signs were identified as statistically distinct between groups in univariate analysis. Multivariate analysis identified that dogs affected with TL-HNPE were typically older, less likely to be chondrodystrophic (62.2 % vs. 91 %), more frequently experiencing a peracute onset (90.2 % vs. 61.9 %) often attributed to a suspected trauma linked with exercise (37.3 % vs. 10.5 %), being less frequently progressive (41.2 % vs. 86.5 %) and with herniated disc material less frequently lateralised (72.6 % vs. 89.5 %) than cases with TL-IVDE. MRI-identifiable intervertebral disc degeneration was found in every TL-IVDE case but only in 60 % of TL-HNPE cases. TL-HNPEs were associated to significantly less spinal cord compression and less hyperalgesia than TL-IVDE.

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.

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.

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.

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.

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.

Dependence of postnatal motoneurones on their targets: review and hypothesis.

Motoneurones are known to die (1) during embryonic development (naturally occurring cell death), (2) early in postnatal development after axonal injury, and (3) as a consequence of disease, such as spinal muscular atrophy or (in later life) amyotrophic lateral sclerosis. Naturally occurring motoneurone death has been extensively investigated, and interaction with the target muscle has emerged as an important factor for survival of embryonic motoneurones. Evidence that this target dependence of motoneurones continues postnatally is discussed in this review, as is the possible nature of the retrograde signal from the muscle. An explanation for the role of the muscle in motoneurone survival is also proposed, which may be applicable in situations where motoneurone death occurs postnatally. This proposal takes into account the changing functional demands imposed on motoneurones as a result of the gradual maturation of the CNS, and suggests that during development the muscle induces the motoneurones to become competent to carry out these requirements.

Cell death of spinal interneurones.

The occurrence of neuronal death during development is well documented for some neuronal populations, such as motoneurones and dorsal root ganglion cells, whose connecting pathways are clearly defined. Cell survival is thought to be regulated largely by target and input connections, a process that serves to match the size of synaptically linked neuronal populations. Far less is known about interneurones. It is assumed that most interneurone populations are excluded from this process because their connections are more diffuse. Recent studies on the rat spinal cord have indicated that interneurone death does occur, both naturally during development and induced following peripheral nerve injury. Here the evidence for spinal interneurone death is reviewed and the factors influencing it are discussed. There are many functional types of interneurones in the spinal cord that may differ in vulnerability to cell death, but it is concluded that for most spinal interneurones the traditional view of target regulation is unlikely. Instead it is proposed that developmental interneurone death in the spinal cord forms part of a plastic response to altered sensory activation rather than a size-matching exercise. There is also emerging evidence that interneurone death may play a more direct role in some neurodegenerative diseases than hitherto considered.

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.

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.

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.

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.

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.

The role of apoptosis and excitotoxicity in the death of spinal motoneurons and interneurons after neonatal nerve injury.

There is evidence that motoneurons which die following neonatal nerve injury in rats do so through an excitotoxic mechanism. In this study, we have investigated whether this excitotoxicity induces motoneuron death by apoptosis. Sciatic motoneurons were prelabelled at birth with the retrograde tracing agent, Fast Blue, and the sciatic nerve was crushed in one leg two days later. At intervals up to 12 days, sections of the lumbar enlargement were analysed for apoptosis using propidium iodide and terminal deoxynucleotidyl transferase biotin-14-UTP nick end labelling techniques. A significant concentration of Fast Blue-labelled apoptotic motoneurons was seen in the area of the sciatic motor pool ipsilateral to the nerve injury, with the majority occurring in the first three days. Comparison of estimates of the time-course of apoptosis with that of motoneuron survival suggest that all motoneuron death induced during the first 12 days occurs by apoptosis and that the process is only recognizable for 2 h. Treatment with the N-methyl-D-aspartate receptor antagonist, dizocilpine maleate, reduced the level of apoptosis by 60%. Taken together, these data show that motoneurons which have been affected by an excitotoxic mechanism die by apoptosis. The apoptotic study also provides evidence, for the first time, that unilateral nerve injury induces motoneuron death in the contralateral sciatic motor pool. Apoptotic interneurons were also seen on both sides of the spinal cord as a result of nerve injury.

Neonatal nerve injury causes long-term changes in growth and distribution of motoneuron dendrites in the rat.

Disruption of neuromuscular contact by nerve-crush during the early postnatal period results in the death of a large proportion of affected motoneurons. Increased activity and abnormal reflex responses are evident in those that survive. We have studied the aberrant dendritic morphology of surviving cells and have attempted to correlate the observed alterations in morphology with the above experimental findings. Motoneurons supplying the extensor hallucis longus muscles of the rat were retrogradely labelled with cholera toxin subunit-B conjugated to horseradish peroxidase. The dendritic tree of labelled cells was analysed in adult animals having undergone unilateral sciatic nerve-crush at birth. Unoperated control animals were also examined. Following nerve-crush at birth, total visible dendritic length was more than 30% smaller than control cells in the transverse plane. This decrease was confined largely to the medially directed segments of the dendritic field and appeared to be due to a reduction in dendritic branching combined with a failure to achieve the correct branch length. There was no overall change in total visible dendritic length in the longitudinal plane, but a reorientation of dendrites in favour of rostrodorsal regions was observed. There was no alteration in dendritic length in cells contralateral to the nerve injury. These results show that nerve injury during early postnatal development produces lasting changes in the distribution of motoneuron dendrites. The localized nature of these changes may explain the altered activity and induced death of motoneurons seen after neonatal nerve-crush.

Evidence for age-dependent changes in motoneuron dendritic morphology following neonatal nerve-crush in the rat.

Motoneurons supplying the extensor hallucis longus muscle of the rat were temporarily separated from the muscle by sciatic nerve-crush at five days postnatally. Such treatment permanently alters the reflex response of the affected motoneurons without the large-scale cell death associated with nerve-crush at birth. After reinnervation, the motoneurons were retrogradely labelled with cholera toxin subunit-B conjugated to horseradish peroxidase and the dendritic tree of each labelled cell was analysed. When compared to normal data, significantly higher levels of dendritic density were observed in the rostrodorsally orientated parts of the dendritic field. This was similar to that found previously for the same motor pool after nerve-crush at birth. However, in other parts of the field where a lower dendritic density was found after nerve-crush at birth, no change was seen after nerve-crush at five days. These data present evidence for the influence of sensory afferents on the development of motoneuron dendrites. Taken together with the previous findings after nerve-crush at birth, we suggest that the differential dendritic changes caused by neonatal nerve lesion contribute to an imbalance in the pattern of excitatory and inhibitory inputs to the motoneuron, which results either in cell death, or the abnormal activity seen in those motoneurons which survive.