Functional localization of epileptic foci in cats using manganese-enhanced MRI

Objective： To determine the encephalic region correlated with epilepsy by manganese-enhanced MRI （MEMRI） and determine the correlation of epilepsy with calcium overloading. Methods： The cats were divided into two groups. The first group underwent EEG examination and ethological observation. The second group underwent MEMRI measurement. Signal enhanced encephalic regions were sectioned. Results： The achievement ratio of convulsive cats intramusclelarly injected with PTZ was 80%. MEMRI showed diffuse signal enhancement in the cerebral cortex of the cats with generalized tonic-clonic convulsive seizures compared with control animals. The enhancement rate of frontal-parietal-occipital lobe was 34.6% and 22.9% in temporl lobe compared with the control groups. Signal enhancement on frontal-parietal lobe persisted for 24 h after epileptic seizures were induced. The neurons of enhanced encephalic regions showed obvious degeneration and necrosis. Conclusion： Seizures can be induced in cats by intramuscular injection of PTZ （55 mg/kg）. Frontal-parietal lobe is the correlated encephalic regions of epilepsy. MEMRI plays an important role in localizing and revealing pathogenesis of epileptic seizures.

The Traf2 and NcK interacting kinase inhibitor NCB-0846 suppresses seizure activity involving the decrease of GRIA1

Epilepsy,one of the most common neurological disorders,is characterized by spon-taneous recurrent seizures.Temporal lobe epilepsy(TLE)is one of the most common medically intractable seizure disorders.Traf2-and NcK-interacting kinase(TNIK)has recently attracted attention as a critical modulation target of many neurological and psychiatric disorders,but its role in epilepsy remains unclear.In this study,we hypothesized the involvement of TNIK in epilepsy and investigated TNIK expression in patients with intractable TLE and in a pilocarpineinduced rat model of epilepsy by western blotting,immunofluorescence,and immunohistochemistry.A pentylenetetrazole(PTZ)-induced epilepsy rat model was used to determine the effect of the TNIK inhibitor NCB-0846 on behavioral manifestations of epilepsy.Coimmunoprecipitation(Co-IP)/mass spectrometry(MS)was used to identify the potential mechanism.Through Co-IP,we detected and confirmed the main potential TNIK interactors.Subcellular fractionation was used to establish the effect of NCB-0846 on the expression of the main interactors in postsynaptic density(PSD)fractions.We found that TNIK was primarily located in neurons and decreased significantly in epilepsy model rats and TLE patients compared with controls.NCB-0846 delayed kindling progression and decreased seizure severity.Co-IP/MS identified 63 candidate TNIK interactors in rat hippocampi,notably CaMKIl.Co-IP showed that TNIK might correlate with endogenous GRIA1,SYN2,PSD-95,CaMKIV,GABRG1,and GABRG2.In addition,the significant decrease in GRIA1 in hippocampal total lysate and PSDs after NCB-0846 treatment might help modify the progression of PTZ kindling.Our results suggest that TNIK contributes to epileptic pathology and is a potential antiepileptic drug target.

Effects of coronavirus disease 2019 vaccination on seizures in patients with epilepsy

Background:Given that seizures may be triggered by vaccination,this study aimed to evaluate the risk and correlative factors of seizures in patients with epilepsy(PWE)after being vaccinated against coronavirus disease 2019(COVID-19).Methods:This study retrospectively enrolled PWE who were vaccinated against COVID-19 in the epilepsy centers of 11 hospitals in China.We divided the PWE into two groups as follows:(1)patients who developed seizures within 14 days of vaccination were assigned to the SAV(with seizures after vaccination)group;(2)patients who were seizure-free within 14 days of vaccination were assigned to the SFAV(seizure-free after vaccination)group.To identify potential risk factors for seizure reccurence,the binary logistic regression analysis was performed.Besides,67 PWE who had not been vaccinated were also included for elucidating the effects of vaccination on seizures recurrence,and binary logistic regression analysis was performed to determine whether vaccination would affect the recurrence rate of PWE who had drug reduction or withdrawal.Results:The study included a total of 407 patients;of which,48(11.8%)developed seizures within 14 days after vaccination(SAV group),whereas 359(88.2%)remained seizure-free(SFAV group).The binary logistic regression analysis revealed that duration of seizure freedom(P<0.001)and withdrawal from anti-seizure medications(ASMs)or reduction in their dosage during the peri-vaccination period were significantly associated with the recurrence of seizures(odds ratio=7.384,95%confidence interval=1.732–31.488,P=0.007).In addition,32 of 33 patients(97.0%)who were seizure-free for more than three months before vaccination and had a normal electroencephalogram before vaccination did not have any seizures within 14 days of vaccination.A total of 92(22.6%)patients experienced non-epileptic adverse reactions after vaccination.Binary logistic regression analysis results showed that vaccine did not significantly affect the recurrence rate of PWE who had the behavior of ASMs dose reduction or withdrawal(P=0.143).Conclusions:PWE need protection from the COVID-19 vaccine.PWE who are seizure-free for>3 months before vaccination should be vaccinated.Whether the remaining PWE should be vaccinated depends on the local prevalence of COVID-19.Finally,PWE should avoid discontinuing ASMs or reducing their dosage during the peri-vaccination period.