Résumé
Anti-N-methyl-D-aspartate receptor encephalitis is severe diffuse encephalitis caused by cerebrospinal fluid(CSF)antibodies against the GluN1 subunit of the NMDAR.Pediatric NMDAR encephalitis is mainly characterized by neurological symptoms such as dyskinesia, ataxia and epilepsy.Auxiliary examinations of the patients show positive CSF IgG antibodies, EEG slow waves and metabolic changes in FDG-PET/CT.But there is lacking of clinical biomarkers for early diagnosis of children with atypical symptoms and negative antibody.Immunotherapy is effective for most children and early treatment can improve prognosis remarkably.At the same time, antipsychotic drugs and antiepileptic drugs can treat children with psycho behavioral symptoms and seizures.However, some patients are refractory to conventional therapies and have neurological sequela even after the application of multiple immunosuppressants.Therefore, more further studies are needed to clarify the pathogenesis and find biomarkers for early diagnosis of pediatric patients.This article reviews the pathogenesis, clinical characteristics, diagnosis and treatments of the disease.
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Objective To explore the effect of human leukocyte antigen B* genotype and age on serum homocysteine (Hcy) levels in children with seizures or epilepsy. Methods Fifteen children with seizures or epilepsy in whom HLA-B*15:02 genotype was detected during October 2015 to June 2016 were included. The plasma Hcy concentration in children with different genotypes was compared. The association of Hcy concentration and age was performed by linear-regression analysis. Results The mean concentration of Hcy was 8.38±4.23 μmol/L in children not carrying HLA-B*15:02 gene, which was obviously higher than that in children carrying HLA-B*15:02 gene 13.03±0.97 μmol/L (P<0.05). The Hcy concentration increased with the age (r2 =0.29, P<0.05). Conclusions Elder children with seizures or epilepsy carrying HLA-B*15:02 gene tend to have higher Hcy concentration and increased potential risk of disease. HLA-B*15:02 gene type and age can predict the changes of Hcy concentration in children with convulsions.
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Objective To identify clinical predictive factors in intractable childhood epilepsy,to provide some evidence for its early diagnosis.Methods Six hundred and twenty-four children with newly diagnosed epilepsy were retrospectively identified in Xinhua Hospital Affiliated to Shanghai Jiaotong University Medical School(1993-2009).The epileptic children were divided into a drug-responsive epilepsy group (n =584) and an intractable epilepsy group (n =40).Clinical data of patients were retrospectively analyzed,including the gender,age,pathogen,inducement,number of pre-treatment seizures,seizure type,seizure type change,seizure duration,family history,previous history,physical examination,brain CT and initial electroencephalogram(EEG) findings.Single factor analysis and Logistic regression analysis were made in 2 groups.Results Strong univariate associations suggested that some factors could increase the risks of intractable epilepsy:symptomatic or cryptogenic epilepsy,mental retardation,type of infantile spasm,positive neurological examination and large absolute number of pre-treatment seizures,and changes in seizure types in the course of the disease.With multiple Logistic regression,independent predictors of intractability were symptomatic or cryptogenic etiology(OR =3.61),large absolute number of pre-treatment seizures and changes in seizure types in the course of the disease(OR =4.76).Conclusions It's necessary to be wary of intractable epilepsy and to adjust therapy accordingly when seizures were uncontrollable and accompanied by one or more conditions such as symptomatic or cryptogenic epilepsy,large absolute number of pre-treatment seizures,changes in seizure types in the course of the disease.
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Objective To establish the population pharmacokinetics(PPK)model of Lamotrigine(LTG)in children with epilepsy in China for promoting individualized dosage regimen. Methods The sparse data of LTG serum concentrations from 60 pediatric patients with epilepsy were collected. One hundred and fourteen serum concentration points were divided into LTG+valproic acid (VPA) group(n=56),LTG+enzymatic inducer(E1)group(n=26),LTG+EI+VPA group(n=16)and single LTG group(n=16).The serum drug concentrations were the clinical routinely tested steadv state concentrations.The LTG PPK parameters were calculated using the non-parametric expectation maximization(NPEM) Program of USC*PACK software,and then a PPK model was established. Based on this model,LTG serum concentrations were predicted with Bayesian fitting program of USC*PACK software.Mean prediction error(MPE)and mean squared prediction error(MSPE) were calculated to evaluate the accuracy and precision of the concentration prediction and to valid the PPK model.Results The greatest likelihood was-192.87.Optimum PPK parameters were:Ka=(1.97 1.66)h~(-1);Vs=(1.07±0.89)L/kg;Kel=(0.05±0.05)h~(-1).The linear regression function Y_(OBS)=-0.09+1.05 Y_(PRED)(R~2=0.98,P<0.001),and determination of coefficient was 0.98.MPE was-0.16 g/mL,and MSPE was 0.28(μg/mL)~2.Conclusion A PPK model of LTG in children with epilepsy in China can be successfully established using the USC*PACK software, based on which LTG serum concentrations can be predicted accurately with a Bayesian approach.