Evaluation of IL-1ß levels in epilepsy and traumatic brain injury in dogs.

BACKGROUND: Epilepsy is a common neurological disease in dogs affecting approximately 0.6-0.75% of the canine population. There is much evidence of neuroinflammation presence in epilepsy, creating new possibilities for the treatment of the disease. An increased expression of interleukin-1 beta (IL-1ß) was reported in epileptogenic foci. We hypothesized that there is an elevation of IL-1ß in serum and CSF of dogs with epilepsy, as well as in serum of dogs with TBI, reflecting involvement of this cytokine in pathophysiology of naturally occurring canine epilepsy in a clinical setting. RESULTS: IL-1ß levels were evaluated in CSF and serum of six healthy and 51 dogs with epilepsy (structural and idiopathic). In 16 dogs with TBI, only serum was tested. IL-1ß concentrations in CSF were not detectable. Serum values were not elevated in dogs with TBI in comparison to healthy controls (p > 0.05). However, dogs with epilepsy had increased levels of IL-1ß in serum (p = 0.003) regardless of the underlying cause of the disease (p = 0.0045). There was no significant relationship between the variables and IL-1ß levels. Statistically noticeable (p = 0.0630) was that approximately 10% of dog with epilepsy (R2 = 0.105) had increased seizure frequency and IL-1ß elevation. CONCLUSION: Increased IL-1ß levels were detected in the peripheral blood in dogs with idiopathic and structural epilepsy leading to the assumption that there is an involvement of inflammation in pathophysiology of epilepsy which should be considered in the search for new therapeutic strategies for this disease. However, to better understand the pathogenic role of this cytokine in epilepsy, further evaluation of IL-1ß in brain tissue is desired.

Grey matter volume in healthy and epileptic beagles using voxel-based morphometry - a pilot study.

BACKGROUND: One of the most common chronic neurological disorders in dogs is idiopathic epilepsy (IE) diagnosed as epilepsy without structural changes in the brain. In the current study the hypothesis should be proven that subtle grey matter changes occur in epileptic dogs. Therefore, magnetic resonance (MR) images of one dog breed (Beagles) were used to obtain an approximately uniform brain shape. Local differences in grey matter volume (GMV) were compared between 5 healthy Beagles and 10 Beagles with spontaneously recurrent seizures (5 dogs with IE and 5 dogs with structural epilepsy (SE)), using voxel-based morphometry (VBM). T1W images of all dogs were prepared using Amira 6.3.0 for brain extraction, FSL 4.1.8 for registration and SPM12 for realignment. After creation of tissue probability maps of cerebrospinal fluid, grey and white matter from control images to segment all extracted brains, GM templates for each group were constructed to normalize brain images for parametric statistical analysis, which was achieved using SPM12. RESULTS: Epileptic Beagles (IE and SE Beagles) displayed statistically significant reduced GMV in olfactory bulb, cingulate gyrus, hippocampus and cortex, especially in temporal and occipital lobes. Beagles with IE showed statistically significant decreased GMV in olfactory bulb, cortex of parietal and temporal lobe, hippocampus and cingulate gyrus, Beagles with SE mild statistically significant GMV reduction in temporal lobe (p < 0.05; family- wise error correction). CONCLUSION: These results suggest that, as reported in epileptic humans, focal reduction in GMV also occurs in epileptic dogs. Furthermore, the current study shows that VBM analysis represents an excellent method to detect GMV differences of the brain between a healthy dog group and dogs with epileptic syndrome, when MR images of one breed are used.

Clinical evaluation of a combination therapy of imepitoin with phenobarbital in dogs with refractory idiopathic epilepsy.

BACKGROUND: Imepitoin was tested as a combination treatment with phenobarbital in an open-label mono-centre cohort study in dogs with drug-resistant epilepsy. Diagnosis of idiopathic epilepsy was based on clinical findings, magnetic resonance imaging and cerebrospinal fluid analysis. Three cohorts were treated. In cohort A, dogs not responding to phenobarbital with or without established add-on treatment of potassium bromide or levetiracetam were treated add-on with imepitoin, starting at 10 mg/kg BID, with titration allowed to 30 mg/kg BID. In cohort B, the only difference to cohort A was that the starting dose of imepitoin was reduced to 5 mg/kg BID. In cohort C, animals not responding to imepitoin at >20 mg/kg BID were treated with phenobarbital add-on starting at 0.5 mg/kg BID. RESULTS: The add-on treatment resulted in a reduction in monthly seizure frequency (MSF) in all three cohorts. A reduction of ≥50% was obtained in 36-42% of all animals, without significant difference between cohorts. The lower starting dose of 5 mg/kg BID imepitoin was better tolerated, and an up-titration to on average of 15 mg/kg BID was sufficient in cohort A and B. In cohort C, a mean add-on dose of 1.5 mg/kg BID phenobarbital was sufficient to achieve a clinically meaningful effect. Six dogs developed a clinically meaningful increase in MSF of ≥ 50%, mostly in cohort A. Neither imepitoin nor phenobarbital add-on treatment was capable of suppressing cluster seizure activity, making cluster seizure activity an important predictor for drug-resistance. CONCLUSION: A combination treatment of imepitoin and phenobarbital is a useful treatment option for a subpopulation of dogs with drug-resistant epilepsy, a low starting dose with 5 mg/kg BID is recommended.