Wakefield A J, Murch S H, Anthony A, Linnell J, Casson D M, Malik M, Berelowitz M, Dhillon A P, Thomson M A, Harvey P, Valentine A, Davies S E, Walker-Smith J A
Inflammatory Bowel Disease Study Group, University Department of Medicine, Royal Free Hospital and School of Medicine, London, UK.
Lancet. 1998 Feb 28;351(9103):637-41. doi: 10.1016/s0140-6736(97)11096-0.
We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder.
12 children (mean age 6 years [range 3-10], 11 boys) were referred to a paediatric gastroenterology unit with a history of normal development followed by loss of acquired skills, including language, together with diarrhoea and abdominal pain. Children underwent gastroenterological, neurological, and developmental assessment and review of developmental records. Ileocolonoscopy and biopsy sampling, magnetic-resonance imaging (MRI), electroencephalography (EEG), and lumbar puncture were done under sedation. Barium follow-through radiography was done where possible. Biochemical, haematological, and immunological profiles were examined.
Onset of behavioural symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 children, with measles infection in one child, and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas. Behavioural disorders included autism (nine), disintegrative psychosis (one), and possible postviral or vaccinal encephalitis (two). There were no focal neurological abnormalities and MRI and EEG tests were normal. Abnormal laboratory results were significantly raised urinary methylmalonic acid compared with age-matched controls (p=0.003), low haemoglobin in four children, and a low serum IgA in four children.
We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.
我们对一系列患有慢性小肠结肠炎和发育倒退性障碍的儿童进行了研究。
12名儿童（平均年龄6岁[范围3 - 10岁]，11名男孩）被转诊至儿科胃肠病科，他们曾有正常发育史，随后出现包括语言在内的后天技能丧失，伴有腹泻和腹痛。这些儿童接受了胃肠病学、神经学和发育评估，并查阅了发育记录。在镇静状态下进行了回结肠镜检查和活检采样、磁共振成像（MRI）、脑电图（EEG）及腰椎穿刺。尽可能进行了钡剂通过造影检查。检查了生化、血液学和免疫学指标。
家长认为，12名儿童中有8名出现行为症状与麻疹、腮腺炎和风疹疫苗接种有关，1名与麻疹感染有关，另1名与中耳炎有关。所有12名儿童均有肠道异常，从淋巴结节增生到口疮样溃疡不等。组织学显示，11名儿童结肠有散在慢性炎症，7名儿童回肠有反应性淋巴组织增生，但无肉芽肿。行为障碍包括自闭症（9名）、瓦解性精神病（1名）以及可能的病毒感染后或疫苗接种后脑炎（2名）。无局灶性神经异常，MRI和EEG检查正常。异常实验室结果包括与年龄匹配对照组相比尿甲基丙二酸显著升高（p = 0.003），4名儿童血红蛋白低，4名儿童血清IgA低。
我们在一组先前正常的儿童中发现了相关的胃肠疾病和发育倒退，其时间上通常与可能的环境触发因素有关。
