Lara Matiasek

Treatment with gabapentin of 11 dogs with refractory idiopathic epilepsy

Eleven dogs diagnosed with refractory idiopathic epilepsy were treated orally with gabapentin for a minimum of three months at an initial dose of 10 mg/kg every eight hours. They were all experiencing episodes of generalised tonic-clonic seizures and had been treated chronically with a combination of phenobarbital and potassium bromide at doses sufficient to reach acceptable therapeutic serum levels without causing significant side effects. In each dog, the number of seizures per week, the average duration of the seizures and the number of days on which seizures occurred were compared for the three months before and after they were treated with gabapentin. A minimum 50 per cent reduction in the number of seizures per week was interpreted as a positive response to gabapentin, and six of the dogs showed a positive response. After the addition of gabapentin, both the number of seizures per week (P= 0·005) and the number of days with any seizures in a one-week period (P=0·03) were significantly reduced. Mild side effects of ataxia and sedation were observed in five of the dogs, but they were not severe enough to warrant the treatment being discontinued during the trial.

Necrotizing Cerebellitis and Cerebellar Atrophy Caused by Neospora caninum Infection: Magnetic Resonance Imaging and Clinicopathologic Findings in Seven Dogs

BACKGROUND Adult dogs with neosporosis can develop a variety of neurologic signs. No area of predilection within the nervous system so far has been identified in adult dogs. OBJECTIVES To document neosporosis as a cause of progressive cerebellar ataxia and cerebellar atrophy in dogs. ANIMALS Seven client-owned dogs. METHODS Retrospective, descriptive study. RESULTS Age at diagnosis ranged from 1 year 6 months to 9 years 11 months. Neuroanatomic localization indicated cerebellar and brainstem disease in 6 dogs and a central vestibular lesion in 1 dog. In all 7 dogs, there was moderate to marked bilaterally symmetrical cerebellar atrophy, with the atrophied cerebellum being surrounded by a region of T2-weighted hyperintense and T1-weighted hypointense signal. Cerebrospinal fluid (CSF) analysis in all but 1 dog showed mononuclear pleocytosis and high protein concentration. Polymerase chain reaction testing for Neospora caninum performed on the CSF was positive in 4/5 dogs tested and there was a high titer of serum antibodies to N. caninum (> or = 1 : 800) in all 6 dogs tested. Postmortem examination in 1 dog confirmed cerebellar atrophy and multifocal nonsuppurative encephalitis with areas of malacia and leptomeningitis. All of the remaining 6 dogs were treated with some combination of clindamycin, trimethoprim, sulfadiazine, and pyrimethamine. Two dogs were euthanized because of deterioration or relapse of neurologic signs, but treatment of the remaining 4 dogs resulted in improvement (3 dogs) or resolution (1 dog) of neurologic signs. CONCLUSIONS AND CLINICAL IMPORTANCE Neosporosis is an important cause of progressive cerebellar ataxia and cerebellar atrophy in adult dogs.

Ki-67 and vascular endothelial growth factor expression in intracranial meningiomas in dogs.

BACKGROUND Tumor proliferation in human intracranial meningiomas can be defined by the reactivity of the monoclonal antibody MIB-1 to the Ki-67 antigen. Vascular endothelial growth factor (VEGF), a pro-angiogenic factor, is a predictive marker for survival of dogs with intracranial meningiomas. HYPOTHESIS Ki-67 is expressed in canine intracranial meningiomas and is associated with VEGF expression. Ki-67 expression is a prognostic marker for patient outcome. ANIMALS Seventy client-owned dogs with WHO grade I intracranial meningiomas. METHODS Retrospective study assessing the degree of immunostaining for Ki-67 by MIB-1 and VEGF expression in intracranial meningioma tissue from dogs. MIB-1 Labeling Index (LI) was calculated with Image J NIH-software. Extent, intensity, and distribution of VEGF-expression was assessed semiquantitatively. Cross tabulations with Fishers exact tests and nonparametric Spearmans rank correlations were performed to identify associations between VEGF expression and MIB-1 LI. Fifteen dogs underwent postsurgical radiotherapy and were included in survival analysis. The effect of MIB-1 LI on survival was examined by Kaplan-Meier and Cox proportional hazards regression procedures. RESULTS Ki-67 staining was positive in 91% (64/70) and VEGF expression was detected in 96% (67/70). There was no significant association between VEGF expression and MIB-1 LI. MIB-1 LI was not associated with survival. CONCLUSIONS AND CLINICAL IMPORTANCE MIB-1 antibody can be used to document cell proliferation in intracranial meningiomas in dogs, but does not predict outcome. No association between VEGF as a marker of angiogenesis and tumor proliferation was found. Angiogenesis might be a more important predictor of meningioma activity in dogs than is Ki-67.

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.

Clinical Course of Acute Canine Polyradiculoneuritis Following Treatment with Human IV Immunoglobulin

Treatment of dogs with acute canine polyradiculoneuritis (ACP) is restricted to physical rehabilitation and supportive care. In humans with Guillain-Barré syndrome, the counterpart of ACP, randomized trials show that IV immunoglobulin (IVIg) speeds recovery. The authors of the current study hypothesized that dogs with ACP would tolerate IVIg well and recover faster than dogs managed with supportive treatment only. Sixteen client-owned dogs with ACP were treated with IVIg, and 14 client-owned dogs served as a retrospective control group. Diagnosis was confirmed using clinical features, electrodiagnostics, cerebrospinal fluid analysis, and muscle/nerve biopsies. The duration of the initial progressive phase, the time from IVIg administration until the dogs were ambulating without assistance, and the duration of the complete episode were evaluated. Adverse reactions (anaphylaxis, mild hematuria) were observed in two dogs. Dogs treated with IVIg were ambulating without assistance after a median of 27.5 days (range, 15-127 days) from onset of clinical signs. The control group was ambulatory without assistance at a median of 75.5 days (range, 5-220 days). Even though this result is not statistically significant, there is a clear trend toward faster recovery in dogs treated with IVIg.

Clinical and magnetic resonance imaging findings in 92 cats with clinical signs of spinal cord disease

Medical records of 92 cats presented with clinical signs of spinal cord disease, which had undergone magnetic resonance imaging (MRI), were reviewed. The cats were grouped into seven categories based upon the diagnosis suggested by results of MRI, cerebrospinal fluid analysis and other diagnostic procedures: neoplastic (n=25), inflammatory or infectious (n=13), traumatic (n=8), vascular (n=6), degenerative (n=5), anomalous (n=3) and those with an unremarkable MRI (n=32). There were two independent predictors of abnormal MRI findings: severity of clinical signs and presence of spinal pain. Abnormal MRI findings and speed of onset of disease were significantly associated with survival. For the 32 cats with unremarkable MRI findings, only nine died due to spinal disease and, therefore, the median survival time (MST) was not reached (lower 95% confidence interval (CI)=970 days). For the 60 cats with abnormal MRI findings, 37 died due to their disease and the MST was 138 days (95% CI: 7–807).

Prevalence, heritability and genetic correlations of congenital sensorineural deafness and pigmentation phenotypes in the Border Collie

The objectives of this study were to estimate prevalence, heritability and genetic correlations of congenital sensorineural deafness (CSD) and pigmentation phenotypes in the Border Collie. Entire litters of Border Collies that presented to the Animal Health Trust (1994-2008) for assessment of hearing status by brain stem auditory evoked response (BAER) at 4-10 weeks of age were included. Heritability and genetic correlations were estimated using residual maximum likelihood (REML). Of 4143 puppies that met the inclusion criteria, 97.6% had normal hearing status, 2.0% were unilaterally deaf and 0.4% were bilaterally deaf. Heritability of deafness as a trichotomous trait (normal/unilaterally deaf/bilaterally deaf) was estimated at 0.42 using multivariate analysis. Genetic correlations of deafness with iris colour and merle coat colour were 0.58 and 0.26, respectively. These results indicate that there is a significant genetic effect on CSD in Border Collies and that some of the genes determining deafness also influence pigmentation phenotypes.

Diagnostic utility of cerebrospinal fluid immunocytochemistry for diagnosis of feline infectious peritonitis manifesting in the central nervous system

Objectives The aim of the study was to evaluate whether an ante-mortem diagnosis of central nervous system (CNS) feline infectious peritonitis (FIP) is possible via immunocytochemical staining (ICC) of feline coronavirus antigen (FCoV) within macrophages of cerebrospinal fluid (CSF). Methods Prospectively, CSF samples of 41 cats were investigated, including cats with histopathologically confirmed FIP and neurological signs (n = 10), cats with confirmed FIP without CNS involvement (n = 11), cats with neurological signs but another confirmed CNS disease (n = 17), and cats without neurological signs and a disease other than FIP (n = 3). ICC staining of CSF macrophages was performed in all cats. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of CSF ICC were calculated. Results Of 10 samples from cats with CNS FIP, eight had detectable CSF macrophages, seven of which were positive for FCoV. Ten of 11 samples from cats with confirmed FIP without neurological signs had macrophages in the CSF, with all 10 being ICC-positive. In cats with other CNS disorders, 11/17 had macrophages, two of which stained positively. In cats with diseases other than FIP and without neurological disorders, 2/3 revealed macrophages, with one cat showing positive ICC staining. Diagnosis of FIP via CSF ICC had a sensitivity of 85.0% and a specificity of 83.3%. PPV and NPV were 85.0% and 83.3%. Conclusions and relevance CSF ICC is a highly sensitive test for ante-mortem diagnosis of FIP manifesting in the CNS. However, CNS ICC specificity is too low to confirm FIP and the method should only be applied in conjunction with other features such as CSF cytology. CNS ICC could be helpful to discover pre-neurological stages of CNS FIP.

Nodo-paranodopathy, internodopathy and cleftopathy: Target-based reclassification of Guillain–Barré-like immune-mediated polyradiculoneuropathies in dogs and cats

Recent views on Guillain-Barré syndrome (GBS) question the accuracy of classification into axonal and demyelinating subtypes that represent convergent neurophysiological phenotypes rather than immunological targets. Instead it has been proposed to clarify the primarily affected fibre subunit in nerve biopsies. As nerve biopsies rarely are part of routine work-up in human patients we evaluated tissues taken from companion animals affected by GBS-like polyradiculoneuropathy to screen for distribution of immune cells, targeted fibre components and segregating non-inflammatory lesions. We identified that immune responses were directed either at Schmidt-Lanterman clefts, the paranode-node complex or both. Based on infiltrative and non-inflammatory changes, four subtypes and/or stages were distinguished, some of which indicate localisation of primary target antigens while others represent convergent late stage pictures, as a consequence to epitope spreading. The impact of histological subtyping onto clinical management and prognosis remains to be evaluated in future clinical trials. Natural development and clinical manifestation of large animal dysimmune neuropathy may reflect human Guillain-Barré syndrome more accurately than experimental models and therefore provide complementary clues for translational research.

Axonal neuropathy with unusual clinical course in young Snowshoe cats

Neuropathies in cats are mostly acquired. In comparison to the dog, only very few inherited forms have been described. This case report describes the clinical and diagnostic findings of a suspected inherited feline axonal neuropathy with a very unique clinical course. Two young related male Snowshoe cats were presented with an initially progressive history of recurrent pelvic limb weakness. Electrodiagnostic investigations suggested an axonopathy and muscle–nerve biopsies confirmed axonal degeneration. Over the following 2 years both cats stabilised without any specific treatment, and repeat electrodiagnostic investigations and muscle biopsy in one cat confirmed the tendency for remission.