Clinical features that separate Lyme meningitis from other causes of aseptic meningitis in children include longer duration of headache, the presence of cranial nerve palsies, and cerebrospinal fluid mononuclear cell predominance, results from a single-center study in Rhode Island demonstrated.

Those are key findings from a validation study of a clinical prediction model developed in 2006 to help clinicians distinguish Lyme meningitis from other causes of aseptic meningitis in children. It marks the first time the model has been prospectively evaluated in children living in a Lyme-endemic region of the United States.

The study, which was published in the May 2009 issue of Pediatrics, “validates what clinicians have thought with regard to Lyme disease, that is, we can use acute clinical presentations to help differentiate Lyme meningitis from other causes of aseptic meningitis,” Dr. Sharon Nachman of the department of pediatrics at the State University of New York at Stony Brook wrote in a commentary about the work (Pediatrics 2009;123:1408).

The original prediction model applied in the analysis is a logistic-regression model that uses history, physical, and laboratory findings to predict Lyme meningitis (LM) in children; the model was developed by researchers led by Dr. Robert A. Avery of the department of pediatrics at Jefferson Medical College, Philadelphia (Pediatrics 2006;117:e1-7).

To prospectively validate this model, investigators led by Dr. Aris C. Garro of the division of pediatric emergency medicine at Rhode Island Hospital, Providence, studied 50 children aged 2-18 years who presented to Hasbro Children’s Hospital in Providence with a lumbar puncture for meningitis that showed a cerebrospinal fluid white blood cell count of more than 8 cells/mcL. Cases of definite LM were defined as cerebrospinal fluid pleocystosis with positive Lyme serology confirmed by immunoblot or erythema migrans rash. Cases of possible LM were defined as cerebrospinal fluid pleocytosis with positive cerebrospinal fluid Lyme antibody.

The researchers applied the original prediction model to their cohort. They also used 10% increments of calculated probability of LM to determine sensitivity, specificity, and likelihood ratios for definite and possible LM (Pediatrics 2009;123:e829-34).

The mean age of the 50 children was 10 years, 60% were boys, and 78% were white. Fourteen had definite LM, 6 had possible LM, and 30 had aseptic meningitis.

The researchers found that certain probability percentage ranges could be used to categorize the children’s risk of LM as low, intermediate, or high. For example, calculated probabilities of less than 10% resulted in a 100% negative predictive value (low risk, with a negative likelihood ratio of 0.006); calculated probabilities of 10%-50% placed patients into an intermediate-risk group; and calculated probabilities of greater than 50% placed patients into a high-risk group, with a positive likelihood ratio of 100.

Dr. Garro and his associates also discovered that if a child had less than 7 days of headache, less than 70% mononuclear cells, and no cranial nerve 7 palsy or other cranial neuropathy, the probability of LM was always less than 10%. “We propose this ‘Rule of 7’s’ as an easily remembered set of criteria that clinicians may be able to use to identify patients at low risk of LM,” they wrote. “Future studies should evaluate this rule before it can be adopted into clinical practice.”

The researchers acknowledged certain limitations of the study, including its small sample size and the fact that two-tier serum Lyme disease testing was not required for study entry, “allowing for possible misclassification of cases.”

They concluded that the chief use of the clinical prediction model “is to limit unnecessary use of parenteral antibiotics in patients presenting with meningitis during peak enteroviral and [Lyme disease] seasons. Additional data from a larger, multicenter, prospective study in areas endemic for [Lyme disease] would provide additional validation for the use of this model in clinical practice.”

Funding for the study was provided by the University Emergency Medicine Foundation at Rhode Island Hospital.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

一项来自罗得岛的单中心研究结果表明，小儿莱姆脑膜炎（LM）与其他原因引起的小儿无菌性脑膜炎临床特征的区别包括：头痛持续时间更长、颅神经麻痹以及脑脊液以单核细胞为主。

上述关键发现来自一项验证性研究。该研究旨在验证一个2006年建立的临床预测模型，以帮助临床医生区分小儿莱姆脑膜炎与其他原因引起的小儿无菌性脑膜炎。这也是首项在美国莱姆病流行地区的儿童中评估该预测模型的前瞻性研究。

研究结果在Pediatrics杂志2009年5月刊上发表。纽约州立大学石溪分校儿科的Sharon Nachman博士评论道，该研究“验证了临床医生对莱姆病的看法，也就是说，我们可以根据急性临床表现来区分是莱姆脑膜炎还是其他原因造成的无菌性脑膜炎。”（Pediatrics 2009;123:1408）。

分析中所采用的原始预测模型为logistic回归模型，主要通过病史、体格检查和辅助检查来预测小儿莱姆脑膜炎。该模型由费城杰弗逊医学院儿科的Robert A. Avery博士领导的研究小组建立（Pediatrics 2006;117:e1-7）。

为了前瞻性验证该模型，普罗维登斯罗得岛医院儿童急救部的Aris C. Garro博士领导的小组研究了本区孩之宝儿童医院共50例脑膜炎儿童患者。这些儿童年龄为2～18岁。这些儿童的脑膜炎诊断性腰穿检查结果显示，脑脊液白细胞计数均超过8个细胞/ml。莱姆脑膜炎确诊病例的定义为脑脊液淋巴细胞增多及经游走性红斑或免疫印迹证实莱姆病血清学阳性。疑似病例的定义为脑脊液淋巴细胞增多及脑脊液莱姆抗体阳性。

研究人员在研究队列中除了采用原始预测模型之外，还采用了莱姆脑膜炎计算概率10%的增量来计算对确诊莱姆脑膜炎和疑似莱姆脑膜炎的敏感度、特异度和似然比（Pediatrics 2009;123:e829-34）。

研究纳入的50例儿童平均年龄为10岁；男孩占60%，白人占78%。其中14例确诊莱姆脑膜炎，6例诊断为疑似莱姆脑膜炎，另外30例诊断为无菌性脑膜炎。

研究人员发现，可根据特定的概率百分比范围将儿童莱姆脑膜炎罹患风险分为高、中、低三类。例如，计算所得概率小于10%者，其阴性预测值为100%，阴性似然比为0.006，罹患风险低；计算所得概率为10%～50%者，罹患风险为中；而计算所得概率大于50%者，罹患风险为高，其阳性似然比为100。

Garro博士及其同事还发现，如果小儿头痛持续时间少于7天、单核细胞比例小于70%且无第7对颅神经麻痹或其他颅神经损伤症状，则莱姆脑膜炎罹患概率总是小于10%。他们在文章中写道，“我们建议临床医生可采用 ‘7规则’这个简单易记的标准来判断患者罹患风险是否较低。在将这一规则应用于临床之前尚需进一步研究评估。”

研究人员承认研究还存在一定局限性，包括样本量小以及入组时并未要求做双重的莱姆病血清学检测。因此，“导致可能出现病例分类错误。”

他们最后总结说，该临床预测模型主要用于“在肠道病毒和莱姆病高发季节，减少不必要地使用肠外抗生素治疗脑膜炎。开展于莱姆病流行地区的更大规模多中心前瞻性研究的进一步数据将有助于进一步验证该模型在临床中的应用。”

该研究由罗得岛医院大学急诊医学基金会资助。 

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