目的

探讨儿童Mollaret脑膜炎（MM）的临床特征。

方法

选择2022年3月3日就诊于上海交通大学附属上海儿童医学中心的1例MM 患儿（患儿1）为研究对象。采用回顾性分析方法，对患儿1的病史、入院查体、相关检查结果及诊疗过程等临床资料进行分析。以“Mollaret脑膜炎” “儿童” “Mollaret meningitis” “child”为中、英文关键词，检索万方知识服务平台、中国知网、维普及Pub Med等国内外数据库中MM 患儿相关文献。本次文献检索时限设定为各数据库建库至2024年12月30日。本研究遵循的程序符合2013 年修订的《世界医学协会赫尔辛基宣言》要求。

结果

①患儿1：男性，12岁11个月，因“间断发热半年，头痛2⁺个月”于上海交通大学附属上海儿童医学中心住院治疗。本次入院后，先后采取头孢噻肟、美罗培南、万古霉素、阿昔洛韦抗感染，甘露醇、浓钠降颅压，甲泼尼龙抗炎、丙种球蛋白支持等综合治疗，患儿1病情多次好转，体温缓解期间无不适主诉，但是好转后又不明原因出现发热、头痛等反复发作3次。本次住院期间颅脑MRI检查结果显示，双侧额叶、颞叶、顶枕软脑膜强化，脑膜炎首先考虑；双侧侧脑室旁血管间隙增宽，枕大池稍大。通过腰椎穿刺采集脑脊液进行检查共计9次，其中3次发作期间脑脊液白细胞计数、压力、蛋白均偏高，其余脑脊液指标基本正常；4次脑脊液高通量测序（NGS）、1次脑膜组织NGS均未检出病原体，进行进一步血液学相关检查未发现自身免疫疾病或传染病。患儿1及其父亲全外显子基因测序结果均未见异常。结合患儿1检查结果及病情经过，临床诊断为MM，遂停用所有抗感染药物，仅口服小剂量泼尼松（15 mg/d×7 d，剂量降为10 mg/d×14 d，再降为5 mg/d持续口服）及麦考酚酯胶囊（500 mg/次×2次/d×60 d），出院前1个月患儿1体温平稳，无不适主诉，于2022年6月3日出院。出院后电话随访至2024年5月底，患儿1泼尼松及麦考酚酯胶囊减停1⁺年，无任何不适主诉。②文献复习结果：共计检索到12篇关于儿童MM 研究相关文献，涉及15例MM 患儿（患儿2～16），加上患儿1，共计16例。这16例患儿中，男性为5例，女性为11例；1例年龄不详，其余15例年龄为2岁6个月至18岁；16例患儿均有发热、头痛表现；1例为单纯疱疹病毒（HSV）-1病原体呈阳性，3例为脊柱囊肿所致，其余12例未见明确病因；16例患儿发作期脑脊液白细胞计数均增高，9例脑脊液白细胞计数明显升高，9例发作期脑脊液蛋白明显升高；仅6例在发作期脑脊液中查见Mollaret细胞；5例报道脑脊液压力，其中4例脑脊液压力明显升高；10例在确诊为MM 前被误诊为化脓/病毒性脑膜炎，而采用抗菌药物、抗病毒药物治疗；16例均有多次反复发作史；治疗主要为对因、对症治疗，经治疗后，除患儿2有癫痫发作外，其余15例患儿预后良好。

结论

儿童MM 在临床上罕见，易被误诊；临床上对于＞2次脑膜炎反复发作，发作期脑脊液白细胞计数、蛋白及压力异常，经治疗后短期内恢复者，应考虑MM 可能；在寻找与其可能相关的病因基础上，治疗以对症处理为主。

Objective

To explore the clinical characteristics of Mollaret meningitis（MM）in children.

Methods

One child with MM （child 1）who visited Shanghai Children's Medical Center，Shanghai Jiaotong University on March 3，2022 was selected as the research subject.A retrospective analysis method was adopted to analyze the clinical data such as the medical history，admission physical examination，relevant examination results and diagnosis and treatment process of child 1.With"Mollaret meningitis"and "child"as key words both in Chinese and English，the relevant literature of MM children were searched from Wanfang Knowledge Service Platform，CNKI，VIP and Pub Med.The literature retrieval time was set from the establishment of each database to December 30，2024.The procedures followed in this study was complied with the requirements of the Helsinki DeclarationoftheWorldMedicalAssociation revised in 2013.

Results

①Child 1 is a 12 years and 11 months old boy.He was admitted to Shanghai Children's Medical Center，Shanghai Jiaotong University due to"intermittent fever for half a year and headache for more than 2 months".After admission，the child 1 was treated with comprehensive treatments including cefotaxime，meropenem，vancomycin，and acyclovir for anti-infection，mannitol and concentrated sodium for reducing intracranial pressure，methylprednisolone for anti-inflammation，and immunoglobulin G supportive therapy.The child's condition improved several times，and he had no complaints of discomfort during the period of temperature relief.However，after the improvement，he developed fever and headache for unknown reasons three times.The results of cranial MRI examination showed enhancement of the bilateral frontal，temporal，and parietal-occipital pia mater，and meningitis was considered first；the bilateral paraventricular vascular spaces were widened，and the cistern magna was slightly enlarged.During hospitalization，cerebrospinal fluid was collected by lumbar puncture for examination for a total of 9 times.Among them，the white blood cell count，cerebrospinal fluid pressure and protein were high during 3 attacks，while the rest cerebrospinal fluid indicators were basically normal.No pathogens were detected in four next-generation sequencing（NGS）of cerebrospinal fluid and one NGS of meningeal tissue.Further hematological examinations did not reveal autoimmune or infectious diseases.The whole exome gene sequencing analysis results of child 1 and his father showed no abnormalities.Combined with the child's examination results and the course of the disease，he was clinically diagnosed as MM.Therefore，all anti-infective drugs were discontinued and only low-dose prednisone（15 mg/d×7 d，reduced to 10 mg/d×14 d，and then reduced to 5 mg/d for continuous oral administration）and mycomfetil capsules（500 mg per dose，twice daily，for a total of 60 days）were taken orally.One month before discharge，the temperature of child 1 was stable and there were no complaints of discomfort.The child 1 was discharged on June 3，2022.After discharge，telephone follow-up was conducted until the end of May 2024，he discontinued prednisone and mycophenolate mofetil capsules for more than one year，and there were no complaints of discomfort.②Literature review results：A total of 12 related literature on pediatric MM were retrieved，involving 15 children with MM，including child 1，a total of 16 cases.Among them，5 were male and 11 were female.The age of 1 case was unknown，and the ages of the remaining 15 cases ranged from 2 years and 6 months to 18 years.All of 16 children presented with fever and headache.One case was positive for the pathogen of herpes simplex virus （HSV）-1，three cases were caused by spinal cysts，and remaining 12 cases had no clear cause.The white blood cell counts of cerebrospinal fluid in all of 16 children during the attack period increased，and 9 cases were significantly increased，and the cerebrospinal fluid protein significantly increased in 9 cases during the attack period.Only 6 cases had Mollaret cells detected in the cerebrospinal fluid during the attack period.Cerebrospinal fluid pressure was reported in 5 cases，among which the cerebrospinal fluid pressure was significantly elevated in 4 cases.Ten cases were misdiagnosed as purulent/viral meningitis before being diagnosed with MM and were treated with antibacterial and antiviral drugs.All of 16 cases had a history of multiple recurrent attacks.The treatment mainly focused on etiological and symptomatic treatment.After treatment，except for child 2 who had epileptic seizures，the prognosis of the remaining 15 children was good.

Conclusions

Pediatric MM is rare in clinical practice and is prone to misdiagnosis.Clinically，for those with more than 2 recurrent episodes of meningitis，abnormal white blood cell count，protein and pressure in cerebrospinal fluid during the attack period，and a short-term recovery after treatment，MM should be considered.Treatment of MM child is mainly symptomatic based on finding possible related causes.