A Preliminary Study On Glymphatic System Function In Patients With Epilepsy

Objective Epilepsy is one of the most common and disabling diseases in the central nervous system.Even if epilepsy is diagnosed clearly and appropriate and correct drug treatment is given,about one third of epilepsy patients can’t control their seizures well,which is called drugresistant epilepsy(DRE).Epileptic seizure will lead to the increase of potassium ions,glutamic acid and tau in the extracellular space.During epileptic seizure,the interruption of interstitial fluid circulation,namely glymphatic system,promotes the accumulation of the above metabolic waste,activates glial cells,exacerbates neuroinflammation and epileptic seizure.As an important part of the glymphatic system,astrocyte dysfunction can be observed in patients with epilepsy.We speculate that there was glymphatic dysfunction in patients with generalized tonic-clonic seizure(GTCS).The comorbidities of epilepsy patients significantly affect life quality and the comorbidities of sleep disorders,anxiety,depression and so on are particularly prominent.On the contrary,these comorbidities will also affect the treatment of epilepsy and the glymphatic dysfunction was involved in the comorbidities aboved.The purpose of this study was to explore the functional status of the glymphatic system in patients with epilepsy.MethodsForty-five patients with epilepsy,including 25 patients with drug-resistant epilepsy and33 healthy controls matched by sex and age were included in this study.General demographic data were collected from two groups and magnetic resonance image scanning was completed.Montreal Cognitive Assessment Scale(Mo CA),Hamilton Anxiety Scale(HAMA),Hamilton Depression Scale(HAMD),Epworth Sleepiness Scale(ESS)and Pittsburg Sleep Quality Index(PSQI)were assesed for two groups.Patients also completed the collection of clinical data,including seizure frequence,epileptic discharge index(EDI),the number of antiepileptic drugs(AEDs),hippocampal sclerosis(HS),and the evaluation of epilepsy-related questionnaires or scales,including Sudden Unexpected Death in Epilepsy Risk Inventory(SUDEP-7),National Hospital Seizure Severity Scale(NHS3)and the Kilifi Stigmat Scale for Epilepsy(KSSE),and completed the 24-hour ambulatory EEG monitoring.We selected the index for diffusivity along the perivascular space(ALPS index)to represent the function level of glymphatic system,which was calculated in epilepsy patients and healthy controls and then analyzed between two groups.The correlation between the ALPS index and the evaluation results of the scale was analyzed in patients with epilepsy.Then the ALPS index of patients with epilepsy was analyzed by subgroup based on seizure frequency,EDI,AEDs,and whether the patients were combined with HS.Results[1](1)ALPS index in patients with epilepsy was significantly decreased compared with healthy control group(1.42±0.17 vs.1.51±0.17,P < 0.05).HAMA [5(2,12.5)vs.3(2,4),P < 0.05)and HAMD [5(2,11)vs.2(0,4),P < 0.05] was significantly higher than that of healthy control group;(2)ALPS index in patients with epilepsy was positively correlated with Mo CA score(β=0.013,t=2.353,P < 0.05)and negatively correlated with NHS3score(β=-0.014,t=2.365,P < 0.05).(3)ALPS index in patients with epilepsy had no significant correlation with SUDEP-7,HAMA,HAMD,PSQI,KSSE,ESS scores and age,disease duration,seizure frequency,EDI,AEDs,and HS.[2] An intergroup analysis was performed for ALPS indexes in non-refractory epilepsy,refractory epilepsy,and healthy controls.There was a statistically significant difference in the ALPS index between patients with refractory epilepsy and healthy controls(1.40±0.19 vs.1.51±0.17,P < 0.05),but no significant difference in the ALPS index between patients with non-refractory epilepsy(1.45±0.13)and healthy controls or patients with non-refractory epilepsy and patients with refractory epilepsy.[3](1)ALPS index in patients with DRE was significantly decreased compared with that in healthy control group(1.40±0.19 vs.1.51±0.17,P < 0.05).(2)ALPS index in patients with DRE was positively correlated with Mo CA score(β=0.021,t=3.006,P < 0.05)and negatively correlated with HAMD score(β=-0.008,t=-2.074,P < 0.05).(3)ALPS index of patients with DRE had no significant correlation with NHS3,SUDEP-7,HAMA,PSQI,KSSE,ESS scores and age,disease duration,seizure frequency,EDI,AEDs,and HS.ConclusionThis study suggested that the glymphatic system has significant dysfunction in patients with epilepsy compared with healthy patients,and it worsened as cognitive function declined and seizure attacks aggravated.In patients with drug-resistant epilepsy,no corelation was found bwtween glymphatic system function and the severity of seizure attack,but it worsened as cognitive function declined and depression exacerbated.We spectulated that glymphatic system may involve in the development of epilepsy,and the more severe the seizure,the more obvious the degree of glymphatic dysfunction in epilepsy patients,which resulted in aworsen function of waste clearance in the central nervous system and may function aggravate epilepsy in turn.Improving the glymphatic system function in epilepsy patients may help to control epilepsy.