Th17 cell-mediated immune response in a subpopulation of dogs with idiopathic epilepsy

Background Canine idiopathic epilepsy (IE) is a common neurological disease with severe impact on the owner´s and the dog’s quality of life. A subpopulation of dogs with IE does not respond to antiseizure drugs (non-responder). Th17 cells (T helper cells) and their proinflammatory Interleukin-17 (IL-17) are part of the immune system and previous studies showed their involvement in the pathogenesis of several autoimmune diseases. Non-responder might have an abnormal immune response against structures of the central nervous system. To discover a new aetiology of canine IE and thereby optimising the therapy of intractable IE, this prospective study aimed to investigate Th17 cells and IL-17 in dogs with IE. The underlying hypothesis was that in some dogs with IE a Th17 cell-mediated immune response could be detectable. Methods 57 dogs with IE and 10 healthy dogs (control group, C) were enrolled in the study. EDTA blood was taken to measure Th17 cells by flow cytometry. IL-17 was measured in 35 cerebrospinal fluid (CSF) and 33 serum samples using an enzyme-linked immunosorbent assay (ELISA). It was investigated whether there was a significant increase of stimulated Th17 cells in blood samples or of IL-17 in serum and CSF samples of dogs with IE in comparison to C. Correlations between the amount of Th17 cells/μL or IL-17 and different clinical parameters e.g. seizure frequency, seizure type, seizure severity or treatment response were evaluated. Additionally, Th17 cells/μL were randomly controlled of 17 dogs with IE and were examined for changes over time and in relation to treatment response. Results Ten dogs with IE had strongly elevated stimulated Th17 cells/μL within the blood (>100 Th17 cells/μL). A slight positive correlation between stimulated Th17 cells/μL and seizure severity (p = 0.046; rSpear = 0.27) was proven in these dogs. In addition, 4/10 dogs with elevated Th17 levels experienced cluster seizures and status epilepticus in comparison to 9% of the dogs with non-elevated Th17 levels (<100 Th17 cells/μL). Dogs with IE had significantly higher IL-17 values in CSF and serum samples compared to C (p<0.001; p<0.002; respectively). Conclusion In single dogs with IE, strongly increased amounts of Th17 cells were detectable and dogs with elevated Th17 cells seemed to have a greater risk for experiencing a combination of cluster seizures and status epilepticus. Therefore, an underlying Th17-cell mediated immune response was suspected and hence anti-inflammatory drugs could be indicated in these single cases with intractable epilepsy.

Posterior Reversible Encephalopathy Syndrome (PRES) Associated With COVID-19 Infection—A Case Report and Review

Coronavirus disease 2019 (COVID-19) has caused a large number of systemic complications including a variety of neurological complications. Some of the neurological complications are not known. Posterior reversible encephalopathy syndrome (PRES) is a known acute neurotoxic syndrome causing a wide range of neurological symptoms. If remains untreated, it can potentially become a life-threatening condition. However, it is not a known neurological complication of COVID-19. We describe a presentation of PRES in a patient with positive COVID-19 and presented with altered mental status. A 78-year-old male with history of idiopathic epilepsy was initially admitted with respiratory illness with negative COVID-19 test. Later during his hospitalization, his respiratory condition got worse and his repeat COVID-19 test came back positive. He had continued encephalopathy and was found to have status epilepticus afterward. Magnetic Resonance Imaging brain showed extensive PRES-related changes. His blood pressure remained overall within control without significant fluctuations. No other apparent etiology was identified for PRES except for possible correlation with COVID-19. Clinicians should consider PRES early in their differential diagnoses in patients with severe COVID-19 with continued encephalopathy.

Prevalence, distribution, and clinical associations of suspected postictal changes on brain magnetic resonance imaging in epileptic dogs

OBJECTIVE To determine the prevalence of presumed postictal changes (PC) on brain MRI in epileptic dogs, describe their distribution, and recognize possible correlations with different epilepsy features. ANIMALS 540 client-owned dogs with epilepsy and a complete medical record that underwent brain MRI at 4 veterinary referral hospitals between 2016 and 2019. PROCEDURES Data were collected regarding signalment, seizure type, seizure severity, time between last seizure and MRI, and etiological classification of epilepsy. Postictal changes were considered when solitary or multiple intraparenchymal hyperintense lesions were observed on T2-weighted and fluid-attenuated inversion recovery images and were hypointense or isointense on T1-weighted sequences, which were not confined to a vascular territory and showed no to mild mass effect and no to mild contrast enhancement. RESULTS Sixty-seven dogs (12.4%) showed MRI features consistent with PC. The most common brain sites affected were the piriform lobe, hippocampus, temporal neocortex, and cingulate gyrus. Dogs having suffered cluster seizures or status epilepticus were associated with a higher probability of occurrence of PC, compared to dogs with self-limiting seizures (OR 2.39; 95% confidence interval, 1.33 to 4.30). Suspected PC were detected both in dogs with idiopathic epilepsy and in those with structural epilepsy. Dogs with unknown-origin epilepsy were more likely to have presumed PC than were dogs with structural (OR 0.15; 95% confidence interval, 0.06 to 0.33) or idiopathic epilepsy (OR 0.42; 95% confidence interval, 0.20 to 0.87). Time between last seizure and MRI was significantly shorter in dogs with PC. CLINICAL RELEVANCE MRI lesions consistent with PC were common in epileptic dogs, and the brain distribution of these lesions varied. Occurrence of cluster seizures or status epilepticus, diagnosis of unknown origin epilepsy, and lower time from last seizure to MRI are predictors of suspected PC.

Owner's Perception of Seizure Detection Devices in Idiopathic Epileptic Dogs

Accurate knowledge of seizure frequency is key to optimising treatment. New methods for detecting epileptic seizures are currently investigated in humans, which rely on changes in biomarkers, also called seizure detection devices. Critical to device development, is understanding user needs and requirements. No information on this subject has been published in veterinary medicine. Many dog health collars are currently on the market, but none has proved to be a promising seizure detector. An online survey was created and consisted of 27 open, closed, and scaled questions divided over two parts: part one focused on general questions related to signalment and seizure semiology, the second part focused specifically on the use of seizure detection devices. Two hundred and thirty-one participants caring for a dog with idiopathic epilepsy, were included in the study. Open questions were coded using descriptive coding by two of the authors independently. Data was analysed using descriptive statistics and binary logistic regression. Our results showed that the unpredictability of seizures plays a major part in the management of canine epilepsy and dog owners have a strong desire to know when a seizure occurs. Nearly all dog owners made changes in their daily life, mainly focusing on intensifying supervision. Owners believed seizure detection devices would improve their dog's seizure management, including a better accuracy of seizure frequency and the ability to administer emergency drugs more readily. Owners that were already keeping track of their dog's seizures were 4.2 times more likely to show confidence in using seizure detection devices to manage their pet's seizures, highlighting the need for better monitoring systems. Our results show that there is a receptive market for wearable technology as a new management strategy in canine epilepsy and this topic should be further explored.

Gut Microbiota in Canine Idiopathic Epilepsy: Effects of Disease and Treatment

Epilepsy is one of the most common neurological disorders in humans and dogs. The structure and composition of gut microbiome associated to this disorder has not yet been analyzed in depth but there is evidence that suggests a possible influence of gut bacteria in controlling seizures. The aim of this study was to investigate the changes in gut microbiota associated to canine idiopathic epilepsy (IE) and the possible influence of antiepileptic drugs (AEDs) on the modulation of this microbiota. Faecal microbiota composition was analyzed using sequencing of bacterial 16S rRNA gene in a group of healthy controls (n = 12) and a group of epileptic dogs both before (n = 10) and after a 30-day single treatment with phenobarbital or imepitoin (n = 9). Epileptic dogs showed significantly reduced abundance of GABA (Pseudomonadales, Pseudomonadaceae, Pseudomonas and Pseudomona_graminis) and SCFAs-producing bacteria (Peptococcaceae, Ruminococcaceae and Anaerotruncus) as well as bacteria associated with reduced risk for brain disease (Prevotellaceae) than control dogs. The administration of AEDs during 30 days did not modify the gut microbiota composition. These results are expected to contribute to the understanding of canine idiopathic epilepsy and open up the possibility of studying new therapeutic approaches for this disorder, including probiotic intervention to restore gut microbiota in epileptic individuals.

Abnormal Behavior Episodes Associated With Zonisamide in Three Dogs: A Case Report

Psychiatric adverse effect associated with anti-seizure drugs has been well-recognized in human medicine. This case report describes three dogs with presumptive idiopathic epilepsy presented for abnormal behavior episodes. Abnormal behavior episodes included sudden rage and aggression to the family members, insomnia, restlessness, and/or constant attention-seeking behavior. MRI study and cerebrospinal fluid analysis in two dogs were unremarkable. The abnormal behavior episodes deteriorated along with gradual dose increment of zonisamide and these episodes almost completely disappeared within 5 days after discontinuation of zonisamide. The exact same episodes relapsed within days after re-administration of zonisamide and disappeared again shortly after discontinuation of zonisamide. Dose adjustments of other anti-seizure medications in case 2 did not result in significant changes in these behavior episodes. Although psychiatric adverse effects including aggressive behavior associated with zonisamide are widely recognized in humans, this is the first report in dogs in the clinical setting.

Psychomotor function in children with epilepsy seen at a tertiary hospital in southern Nigeria: does treatment with anti-epileptic drugs have any effect?

Background Psychomotor slowing is more commonly reported in children with epilepsy (CWE) compared to healthy controls. The effect of anti-epileptic drug (AED) treatment on psychomotor abilities of CWE remains controversial. In Nigeria, psychomotor abilities of CWE are scarcely investigated and the impact of AEDs is not known. The present study sought to assess psychomotor performance of CWE compared to healthy controls and to determine any association with seizure characteristics and treatment. Method A comparative cross-sectional study involving 160 children with idiopathic epilepsy and 80 controls aged 6–16 years. Psychomotor function was assessed using reaction times and tapping task of the Iron psychology computerised test battery. The criterion for impairment was fixed at two standard deviations (SD) worse than the mean of age-matched controls. The relationship between seizure variables and psychomotor function was assess with the one-way analysis of variance (ANOVA). Result Fifty-nine (36.9%) CWE had impaired auditory reaction, 50 (31.3%) with impaired visual reaction and 11 (6.9%) had fine motor control impairment. There was no significant difference in psychomotor performance between CWE on AED and the newly diagnosed counterparts yet to start AED treatment (auditory reaction time—p = 0.226; visual reaction time—p = 0.349; tapping task—p = 0.818). AED treatment duration over 5 years was associated with better auditory reaction time (F = 4.631, p = 0.034) in CWE. Also, seizure onset before 5 years of age was associated with slower auditory reaction (F = 4.912, p = 0.028) and verbal reaction (F = 14.560, p < 0.001). Conclusion Nigerian CWE perform less favourably on tests of psychomotor function than healthy controls. The performance of children on AED is not significantly different from those not on AED. Longer duration of AED treatment may result in psychomotor improvement in CWE. CWE should be closely monitored for psychomotor slowness so that deficits can be identified and appropriate interventions instituted.

Hair Magnesium content and its relation to Serum Magnesium level in children with Idiopathic Epilepsy

Objective To measure the level of hair Mg, as well as its level in serum, in patients with epilepsy and compare them to the levels found in non-epileptic age and gender matched children, and to explore any potential correlation between either serum or hair level of magnesium and seizure characteristics in children with idiopathic epilepsy. Methods An observational cross-sectional study including 50 children with idiopathic epilepsy and 100 non-epileptic age and gender matched control subjects. Cases were subjected to full history taking, examination and measurements of serum and hair levels of magnesium, control subjects only had their serum and hair level of magnesium measured as for the cases. Results The mean serum magnesium was 29.11 ± 13.42 ug/ml for cases and 27.67 ± 7.24 ug/ml for controls and the median hair level of magnesium was 42.22 ug/g with IQR of 25.9 - 56.82 for cases and 38.6 ug/g with IQR of 25.21 - 61.25 for controls. No statistically significant difference was observed between both groups as regards either serum or hair magnesium levels. No statistically significant correlation was observed between either hair or serum levels of magnesium and seizure characteristics though the correlations were nearing statistical significance for the hair magnesium content. Conclusion Hair magnesium level may be better correlated to seizure characteristics and control than serum levels in patients with epilepsy.