儿童偏头痛与婴儿肠绞痛史有关

《美国医学会杂志》4月17日发表的一篇报告显示，与因其他原因急诊患者相比，因偏头痛前往急诊室的儿童与青少年具有婴儿期肠绞痛史的比例增加5倍。而在因紧张型头痛前往急诊室的儿童与青少年中，具有婴儿期肠绞痛史者的比例并未增高(JAMA 2013;309:1607-12)。

主要研究者、法国巴黎Robert Debré医院的Silvia Romanello医生指出，上述结果证实了偏头痛与肠绞痛之间的特殊关联。

临床医生和研究人员长期以来一直怀疑肠绞痛和偏头痛这两种疼痛综合征之间存在关联，但始终缺乏深入研究。Romanello医生及来自法国和意大利的合作者围绕这一问题开展了病例对照研究，共纳入了328例儿科患者和471名对照者。

受试者的年龄为6~18岁，在3个月的研究期内因原发性头痛而前往急诊室就诊。共有208例患儿被小儿神经科医生诊断为原发性偏头痛(142例有先兆，其余66例无先兆)，120例患儿被诊断为紧张型头痛。对照者为年龄匹配、同期因轻度创伤前往急诊室的患儿。排除复发性头痛患儿。

研究者分析了所有受试者的医疗记录，寻找婴儿期肠绞痛的诊断。对每名受试者均借助家长问卷证实其病史。结果显示，共有72.6%的原发性偏头痛患儿有婴儿期肠绞痛病史，这一比例在有先兆和无先兆的偏头痛患儿中相似(69.7% vｓ．73.9%)。而在紧张型头痛患儿中，仅有35%在婴儿期曾发生肠绞痛。对照组情况与之相似(26.5%)。

研究者在进一步分析这些数据后发现，婴儿期肠绞痛与偏头痛之间的相关性非常显著，比值比(OR)为6.61，提示二者在病理生理学机制方面具有共通之处。有先兆和无先兆的偏头痛与婴儿期肠绞痛均高度相关，OR值分别为5.73和7.01。而未发现婴儿期肠绞痛与紧张型头痛或轻度创伤相关。

鉴于在儿童中诊断头痛可能并不容易，研究者进行了一项亚组分析以探究诊断中潜在的年龄相关性偏倚，并证实了主体研究的结果：偏头痛与婴儿期肠痉挛的关联在6~12岁儿童和13~18岁青少年中都仍然非常显著。

这项研究并不旨在探究偏头痛与肠绞痛之间关联的可能原因。不过研究者指出，肠绞痛可能是肠道血管周围神经末梢敏化的结果，而偏头痛则是大脑中相似过程的结果。另一种可能性是“已知参与感觉活动调节的分子，例如与偏头痛发作有关的降钙素基因相关肽(CGRP)”也可能通过诱导肠道感觉神经元的神经性炎症而参与腹痛的调节。假如果真如此，那么CGRP拮抗剂等有效镇痛药物或许对肠绞痛和偏头痛的治疗都有帮助。

此外，曲坦类药物已被证明对偏头痛和腹型偏头痛的急性发作都非常有效，或许人们会发现这类药物也可治疗婴儿期肠绞痛。不过，在考虑此类治疗之前还需开展更多研究。不过Romanello医生也承认，尽管婴儿肠绞痛会使婴儿痛苦、父母烦恼，但“目前恐怕难以开展针对这种良性疾病的曲坦类超适应证临床试验”。

研究者无利益冲突披露。

随刊述评：肠绞痛与偏头痛似乎有强烈关联

西北大学的Leon G. Epstein博士和Phyllis C. Zee博士评论指出，该研究回答了一个由来已久的问题，显示出小儿偏头痛与婴儿肠绞痛之间存在明确关联，比值比高达6.61。假如肠绞痛被证实是偏头痛的早期表现，就能解释为何大多数肠绞痛治疗(直接针对胃肠道病因)都效果不佳(JAMA 2013;309:1636-7)。

Zee博士披露了多种利益冲突。

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By: MARY ANN MOON, Clinical Neurology News Digital Network

Children and adolescents who presented to the emergency department with migraine headache were 6 times more likely to have a history of colic during infancy than were those who presented for other reasons, according to a report in the April 17 issue of JAMA.

In contrast, children and adolescents who presented to the ED with tension-type headache showed no increase in the likelihood that they had experienced infantile colic. This confirms the specificity of the association between migraine – not other types of headache – and colic, said Dr. Silvia Romanello of the department of pediatric emergency care and the pediatric migraine and neurovascular diseases unit, Robert Debré Hospital, Paris, and her associates.
 
Researchers and clinicians have long suspected an association between the two pain syndromes of colic and migraine, but such a link has not been well studied. Dr. Romanello and her colleagues at three tertiary-care hospitals in France and Italy examined the association in a case-control study involving 328 pediatric patients and 471 controls.

Subjects were aged 6-18 years and presented to EDs with primary headaches during a 3-month study period. A total of 208 were diagnosed by a pediatric neurologist as having primary migraine (142 without aura and 66 with aura), and 120 were diagnosed as having tension-type headache. The control subjects were patients of the same age who presented during the same period with minor trauma.

Patients with recurrent headaches were excluded from the study.

The medical records of all the study subjects were reviewed for a diagnosis of infantile colic. Parent questionnaires confirmed this history in every case.

A total of 72.6% of the patients with primary migraine had a history of infantile colic. The prevalence of colic was similarly high between those who had migraine with aura (69.7%) and those who had migraine without aura (73.9%).

In contrast, only 35% of the patients with tension-type headache had a history of infantile colic. This prevalence was similar to that in the control group (26.5%), the investigators said (JAMA 2013;309:1607-12).

In a further statistical analysis of the data, the association between infantile colic and migraine was highly significant, with an odds ratio of 6.61. No association was seen between infantile colic and tension-type headache or infantile colic and minor trauma.

A subgroup analysis showed that the association between infantile colic and migraine with aura was highly significant, with an OR of 5.73, as was the association between infantile colic and migraine without aura, which had an OR of 7.01. This finding indicates that the two pain disorders, colic and migraine, share a common pathophysiology, Dr. Romanello and her associates said.

Given that diagnosing headache in children can be challenging, another subgroup analysis was performed to explore any possible age-related bias in diagnosis. The results confirmed those of the main study: The association between migraine and infantile colic remained highly significant in both children aged 6-12 years and adolescents aged 13-18 years.

This study was not designed to explore the possible reasons for the strong association between migraine and colic. However, the investigators noted that colic might result from a sensitization of the perivascular nerve terminals in the gut, much as migraine results from a similar process in the brain.

Another possibility is that "molecules known to be involved in the modulation of sensory activity, such as calcitonin-gene-related peptide (CGRP)," which is released during migraine episodes, also may be involved in modulation of abdominal pain "by inducing the neurogenic inflammation of sensory neurons in the gut." If so, drugs that are CGRP antagonists, which are effective in pain management, may be found helpful for both colic and migraine.

In addition, triptans have proved extremely effective against acute attacks of both migraine and abdominal migraine, and eventually may be found useful for infantile colic. However, much more study is needed before such treatment can be considered. "It is currently difficult to imagine that clinical trials will be conducted with such off-label drugs for the treatment of a benign condition such as infantile colic," even though the condition clearly causes pain in infants and significant stress in parents, Dr. Romanello and her associates said.

No financial conflicts of interest were reported.

Commentary – Link between colic and migraine appears strong

Dr. Leon G. Epstein and Dr. Phyllis C. Zee comment: The report by Romanello and colleagues answers a long-standing question and shows a definite link between pediatric migraine and infantile colic, with an odds ratio of 6.61.

If colic proves to be an early manifestation of migraine, it would explain why most treatments for colic, which have been directed at a gastrointestinal etiology, have consistently been ineffective, they noted.

Dr. Epstein is in the departments of pediatrics and neurology at Northwestern University, Chicago, and the Ann & Robert H. Lurie Children’s Hospital of Chicago. Dr. Zee is in the department of neurology at Northwestern University. Dr. Zee reported numerous ties to industry sources. These remarks were taken from their editorial accompanying Dr. Romanello’s report (JAMA 2013;309:1636-7).