Clinical characteristics of brain tumorrelated epilepsy and factors influencing the identification of epilepsy-associated tumors

Background:To analyze the clinical features of brain tumor-related epilepsy(BTRE)and explore the factors influencing the identification of epilepsy-associated tumor(EAT),in order to advance the clinical understanding of BTRE and EAT.Methods:Intracranial tumor origin and location as well as the type of epilepsy were retrospectively reviewed in 153 BTRE patients.The patients were further divided into the EAT and non-EAT groups,and comparisons were made for age,sex,tumor origin and location,and epilepsy type between the two groups.Results:The 153 BTRE patients were divided into 78 cases with primary intracranial tumor and 75 cases with tumor originating from extracranial metastasis,according to the origin of tumor.According to the location of tumor,116 cases had tumor lesions located in the brain parenchyma,and 37 cases had tumor lesions located in the meninges.Further,in the group with a brain parenchyma location,77 cases had single lobular involvement,and 39 cases had multiple-lobular involvement;84 cases had tumor lesions located in one hemisphere and 32 cases in both hemispheres.According to the type of epilepsy,92 cases had generalized seizures,and 61 cases had focal seizures.The type of epilepsy did not significantly correlate with the origin of intracranial tumor,the location of tumor lesions(in brain parenchyma or meninges)(P>0.05),or the hemispherical location(in one or two hemispheres)of lesions(P>0.05),but was significantly related with the lobular localization of lesions(P<0.05).The 153 cases of BTRE consisted of 87 EAT and 66 non-EAT,with significant differences in the origin,location and type(being glioma/non-glioma)of tumor.Logistic regression analysis showed that the type of tumor(i.e.whether being glioma)served as an independent factor for EAT identification;the lower the World Health Organization grade of glioma,the more likely the EAT is to be diagnosed(P<0.05).Conclusion:The majority of BTRE patients in this study had tumors located in the brain parenchyma.In addition,the patients with generalized seizures outnumbered those with focal seizures,and the type of epilepsy was correlated with the lobular location of tumor lesions.The EATs are mostly low-grade gliomas.

Sphingosine 1-phosphate receptor 1 regulates bloodbrain barrier permeability in epileptic mice

Destruction of the blood-brain barrier is a critical component of epilepsy pathology.Several studies have demonstrated that sphingosine 1-phosphate receptor 1 contributes to the modulation of vascular integrity.However,its effect on blood-brain barrier permeability in epileptic mice remains unclear.In this study,we prepared pilocarpine-induced status epilepticus models and pentylenetetrazol-induced epilepsy models in C57BL/6 mice.S1P1 expression was increased in the hippocampus after status epilepticus,whereas tight junction protein expression was decreased in epileptic mice compared with controls.Intraperitoneal injection of SEW2871,a specific agonist of sphingosine-1-phosphate receptor 1,decreased the level of tight junction protein in the hippocampus of epileptic mice,increased blood-brain barrier leakage,and aggravated the severity of seizures compared with the control.W146,a specific antagonist of sphingosine-1-phosphate receptor 1,increased the level of tight junction protein,attenuated blood-brain barrier disruption,and reduced seizure severity compared with the control.Furthermore,sphingosine 1-phosphate receptor 1 promoted the generation of interleukin-1βand tumor necrosis factor-αand caused astrocytosis.Disruption of tight junction protein and blood-brain barrier integrity by sphingosine 1-phosphate receptor 1 was reversed by minocycline,a neuroinflammation inhibitor.Behavioral tests revealed that sphingosine 1-phosphate receptor 1 exacerbated epilepsy-associated depression-like behaviors.Additionally,specific knockdown of astrocytic S1P1 inhibited neuroinflammatory responses and attenuated blood-brain barrier leakage,seizure severity,and epilepsy-associated depression-like behaviors.Taken together,our results suggest that astrocytic sphingosine 1-phosphate receptor 1 exacerbates blood-brain barrier disruption in the epileptic brain by promoting neuroinflammation.