The Value Of Immunotherapy In Children With Initial Short-term Frequent Seizures

ObjectAnalyze the clinical data and Antibody Prevalence in Epilepsy(APE)score of children with initial short-term and frequent seizures with negative autoantibodies,summarize the clinical characteristics of these children.To explore the clinical application value of immunotherapy and provide reference for the treatment of these children.Materials and Methods1.Clinical data The clinical data of more than 10,000 children with epilepsy admitted to the Department of Pediatric Neurology of Qilu Hospital of Shandong University from June 2019 to June 2022 were reviewed.Through analysis,a total of 16 children with initial,short-term and frequent seizures of drug-resistant epilepsy with negative autoantibodies received immunotherapy.A clinical data collection table was established to collect the basic information,medical history,clinical symptoms,imaging findings,electroencephalogram and other related auxiliary examinations,as well as the treatment and remission of seizures of these children.2.Inclusion criteria As autoimmune epilepsy is rare and rarely reported at home and abroad,there is still no international guideline or expert consensus related to autoimmune epilepsy.Therefore,we formulated the inclusion criteria for this study by reading a large number of relevant literature and combining the children admitted to the clinic.2.1 The course of disease is less than 3 months;2.2 The epileptic seizure emerged in these children patient with high frequency,with the average daily seizure frequency more than 10 times;2.3 Negative serum+cerebrospinal fluid(CSF)neural autoimmune antibody examination;2.4 The development of mental motor was normal before onset.No family disease history,no history of epilepsy caused by tumor,cerebrovascular disease,encephalitis,trauma or metabolic disease and others;2.5 There is no clear history of structural brain abnormalities that lead to seizures;2.6 No good response to ≥ 2 types of ASMs,and later acceptance of systemic immunotherapy.3.Follow-up time The follow-up time of all cases was more than 6 months.4.Immunotherapy regimen Intravenous high-dose methylprednisolone and/or intravenous human immunoglobulin.5.Continue to take anti-seizure medication,analyze the clinical manifestations,auxiliary examination characteristics and APE score of the children,and Immunotherapeutic effect.Results1.General information A total of 16 cases were included in this study.Among them including 10(62.5%)males and 6(37.5%)female.Male:female=1.67:1.The age lied between 1 year and 7 month to 10 years and 11 months,and the median was 3.29 years.2.Epileptic manifestations Focal motor seizures in 13 cases(81.3%);2 cases(12.5%)had generalized tonic-clonic seizures,and one(6.3%)was generalized seizure secondary to focal seizure.Another patient(6.3%)had both special manifestations such as paroxysmal limb pain and panic.The epileptic seizure emerged with high frequency,with the average daily seizure frequency>10 times,and the duration of each seizure is relatively short,usually<1 min.3.Auxiliary examination result3.1 CSF examination All sixteen children patient accepted CSF examination,CSF cytology,routine,biochemical,immune,culture examinations,and no abnormality was reported.3.2 Neuronal autoimmune antibody test The examination of serum+CSF neural autoimmune encephalitis antibody(NMDA-R-Ab,LGI1-Ab,CASPR2-Ab,GABAB-R-Ab,GAD65-Ab,AMPA1-R-Ab,AMPA2-R-Ab)was negative;demyelinating antibody(anti-MOG antibody IgG,anti-AQP4 antibody IgG,anti-MBP antibody IgG,anti-Amphiphysin antibody IgG,anti-Hu antibody IgG,anti-Ri antibody IgG,anti-SOX 1 antibody IgG)was negative.3.3 Brain MRI and electroencephalogram examination In case 5,brain MRI showed a slight enlargement of the temporal horn of the right ventricle;In case 12,the morphological and signal changes of the left medial temporal lobe and hippocampus were observed.Case 13 showed abnormal signals in the left occipital lobe and hippocampus.No abnormality was found in other 13 children patient.Thirteen children patients reported abnormality in electroencephalograph(EEG).Cases 1,2,5,9 and 16 all showed abnormal discharge mainly in the right cerebral hemisphere.Case 3,4 and case 10 showed abnormal discharge in frontal,central and midline areas on both sides during sleep.Cases 6,8 and 14 showed abnormal discharge predominating in the anterior head.In case 7,focal seizures originating in the left central region were detected.The seizure interphase was characterized by anterior head,occipital region,and extensive intermittent δ rhythm release.In case 11,a focal seizure originating in the right frontal region was detected.The interseizure phase shows sharp slow and sharp waves in the anterior head during sleep,especially on the left side.3.4 Other tests All the 16 children included had completed the blood routine examination,c-reactive protein,liver function,kidney function,blood electrolyte,myocardial enzyme,blood ammonia,lactic acid,homocysteine and other laboratory tests,and no obvious abnormalities were found.Among them,10 children completed cellular immunity and humoral immunity tests,and no obvious abnormalities were found.3 children were tested for antibodies related to systemic autoimmune diseases such as antinuclear antibody,and the results were all negative.Screening for genetic metabolic disease was completed in 5 child,and the result was negative.4.APE score All cases should have APE score,4 cases≧4 scores,12 cases<4 scores.5.Antiseizure medicine therapy All sixteen children patient were given 2 or more types of ASMs,and the therapy effect was not good,and the seizures were not reduced.6.Immunotherapy Single high-dose gamma globulin shock in 12 cases,high-dose gamma globulin combined with methylprednisolone shock in 4 cases.7.Immunotherapy results7.1 Immunotherapy for 1 month One month after the first immunotherapy,11 children patient didn’t have epileptic seizure anymore,and one children had occasionally epileptic seizure;Other 4 children patient had obvious decrease in epileptic seizure frequency,and 3 of them were given second immunotherapy,1 declined further treatment for personal reasons.7.2 Immunotherapy for 3 month Three months after the first immunotherapy,15 children patient didn’t have epileptic seizure anymore.Among the 15 children,3 were given secondary immunotherapy one month after the first immunotherapy because their symptoms did not improve significantly,and the seizures were later controlled.One child had occasionally epileptic seizures.Although the second immunotherapy was not given,the frequency of seizures was significantly less than before,the duration and severity of seizures were significantly reduced,and the mental symptoms and cognitive function were also significantly improved.7.3 Immunotherapy for 6 month Six months after the first immunotherapy,the 15 children patient still do not have epileptic seizure,and the leaving one child had occasionally epileptic seizure,but the frequency and duration obviously reduced,and the cognitionand quality of life were significantly improved compared to the past.Conclusions1.For those epileptic children who have an acute onset,well-developed in the past,have high seizures frequency,short seizures duration,no good response to≥2 types of ASMs standard treatment,and excluded other etiological factors.Even if autoimmune antibody screening is negative,the autoimmune epilepsy should be considered.2.For patients with epilepsy with negative autoimmune antibodies,initial short-term frequent seizures and no good response to ASMs,early immunotherapy can achieve good results.