Abstract
Background
Trigemino-autonomic cephalalgias are very rare disorders and even rarer in children and adolescents. We report the onset of paroxysmal hemicrania in a very young girl and reviewed the scientific literature for similar cases.
Findings
We describe the case of a 1.6-year-old girl with left-sided headache attacks fulfilling the criteria of paroxysmal hemicrania including prompt responsiveness to indomethacin. In addition, we detected at least two children for every trigemino-autonomic cephalalgias subtype with an age of under 7 years at the onset of the trigemino-autonomic cephalalgias. Remarkable features were a vast majority of chronic course from onset on and left-sided attacks.
Conclusion
Although very rare, trigemino-autonomic cephalalgias can occur even in very young children under the age of 6 years. This should be known in neuropaediatrics.
Introduction
Trigemino-autonomic cephalalgias (TACs) are typically seen in adults, although it is not very uncommon that adolescents also report these headache disorders (1). There are also reports on children, but these are much rarer and published as single cases (2). We report the case of a very young age of onset in paroxysmal hemicrania and analyse the literature on this topic. If a very young age of onset in TAC is possible, this would be a strong argument for an inherited rather than an acquired liability to these disorders. Further, if TACs can occur in a very young age, neuropaediatricians should be aware not only of migraine but also of other idiopathic headache disorders even in the very young.
In this paper we report the – to our knowledge – youngest case of definite paroxysmal hemicrania and present an overview of other published cases with a very young age of onset in TACs; that is, under the age of 7 years. This limit was chosen since from that age on children are normally going to school and are able to report their symptoms, so the number of detected cases is probably much higher. We were interested in the number of cases of very young children with a TAC in whom the diagnosis can often only be made indirectly. We only enrolled patients in whom the final diagnosis according to ICHD-3 criteria of one of the TACs was made (3); that is, atypical cases, symptomatic cases or probable cases were not considered.
We searched the medical data banks Medline, Web of Science, Embase and textbooks with the search terms cluster headache, paroxysmal hemicrania, hemicrania continua, SUNCT and SUNA together with the term “child*”. All matches were screened for case reports or case series. If the age was below 7 years and the diagnostic criteria of ICHD-3 for the final diagnosis were fulfilled (i.e. excluding probable cases), the case was included no matter which further data were available.
Case report
A 2-year old girl was admitted to our headache clinic by her paediatrician for a second opinion. When she was 1 year and 6 months old she started to develop pain attacks strictly left-sided, the attacks were in the face and accompanied with lacrimation and conjunctival injection only of the left eye. The girl cried during the attacks and behaved like she also did when she had other types of severe pain. She was not yet able to speak adequately and describe her attacks but her parents were convinced that she must have had very severe pain. The attacks occurred occasionally in the first months; that is, less than five attacks every other day as the parents remembered. At the age of 2 years, the attacks became more frequent and finally occurred daily between five and ten times per day. The duration of a single attack was 5–10 minutes. The semiology of the attacks remained the same all the times. The parents had tried several analgesics including ibuprofen, acetaminophen (oral and suppositories), metamizole, and even a low dose of diazepam. Following advice from their paediatrician, 3 to 6 mg amitriptyline in the evening was also tried. Nothing helped to stop the attacks. MRI scan (including T1 and T2 sequences, MR angiography and venography and orbital slices), EEG and neurological examination outside the attacks were normal. There was no family history of any TAC.
After consulting several textbooks, the paediatrician started indomethacin with 25 mg up to three times a day. This abruptly stopped the attacks. At that time, the girl was referred to our tertiary headache clinic, where we could observe an attack and confirmed the diagnosis of paroxysmal hemicrania with a chronic subtype because the patient had daily attacks (without treatment) for more than 12 months at the last follow-up. We advised to taper down the dose of indomethacin. Four months later (at the age of 2 years and 4 months with a body weight of 11.5 kg), the girl still needs indomethacin. With a daily dose 2 × 10 mg or 2 × 12.5 mg, she is free of attacks. Indomethacin is well tolerated. However, the parents are still concerned about side effects, which the young girl is not able to report.
Review of very young cases
We previously reported a boy who was exactly 4 years old when he started to experience typical cluster headache attacks (2). The attacks occurred over an observation period of 5 years unremittingly, so the IHCD-3 diagnosis was chronic cluster headache. Further cases of all children with a very young age at onset of any TAC, whom we found in the literature, are presented in Table 1.
Cases of children with an age of 6 years or younger at onset of a TAC subtype.
nd: no data; m: male; f: female. aIf no specific number of months was given, it is noted as 0.
bFirst symptoms in the age of 1, fulfilling the criteria from the age of 4 on.
cThe subtype episodic versus chronic could not be determined.
We could not identify all demographic features in the case reports or case series published on very young children with a TAC. However, for those parameters where we have data in at least 50% of cases, it is remarkable that 85% of the very young children with a TAC started with a chronic course, which is also confirmed in larger case series on all cluster headache patients with an age of onset under 18 (4). In adulthood, the majority of patients start with an episodic course (5). Another remarkable feature is that the majority of cases (77%) were left-sided, whereas in large case series on cluster headache in adults the majority (about 60%) is right-sided (5). We also detected more female sufferers from cluster headache in that age group (sex ratio 6 to 5), which is uncommon as compared to adults. For paroxysmal hemicrania, the higher prevalence among girls (6 to 2) could be expected.
We found two probable cases of very young children with a TAC. In a 3-month old boy, episodes of typical trigemino-autonomic symptoms in the face were noted with an attack duration of up to 20 minutes (6). The time pattern was, however, not typical for any TAC listed in ICHD-3. Another 5-year-old boy presented with attacks fulfilling the criteria for paroxysmal hemicrania (7). However, again the time pattern did not match any ICHD-3 criteria completely. So, both cases received the diagnosis of probable paroxysmal hemicrania.
Discussion
We detected at least two cases for every subtype of TAC with an age at onset of 6 years or younger. This supports the hypothesis that TACs are an innate liability rather than an acquired syndrome. However, heritability of the TACs is not proven by this fact. Several studies showed no major genetic risk for TACs (8), although a higher familial risk has been shown in epidemiological studies (1). It seems unlikely that environmental factors or social/observational learning can induce TACs in these very young patients.
Onset of TACs in this very young age is certainly very rare. It is completely unknown why some sufferers start so early whereas the vast majority of patients start after the age of about 20. Interestingly, nearly all very young children with a TAC started with a chronic course. We have no explanation for this but believe that this points to a specific (more severe?) pathophysiology. It would be useful to see a long-term follow-up of these children, whether they stay chronic or will convert into episodic. The two probable cases of paroxysmal hemicrania we found in the literature also add to this discussion, since the final diagnosis could not be made only because of the time pattern, not because of the clinical features.
Another interesting feature in our case series, the clear predominance of left-sided TACs in these very young children, remains obscure. We cannot see any reason why in very young patients with a TAC the left side should be more affected than in patients with adult onset. However, although the number is small, it is from a statistical point of view unlikely that this is just by chance.
Apart from the course and left-sided predominance, we could not detect any relevant differences of the clinical picture as compared to adults. For paroxysmal hemicrania, the daily dose of indomethacin in children was reported to be 3 mg per kg body weight (22). Our patient needed about 2 mg per kg body weight. In adults, the daily dose of indomethacin also ranges between 2 and 3 mg per kg body weight. It is, however, important to carefully observe the indomethacin dose needed by children since side effects such as restlessness, sweating, sleep disturbances and gastrointestinal discomfort can occur, and children are not able to report their side effects in as much detail as adults. In particular, gastrointestinal side effects could be overlooked in children. It would therefore be useful if the treating physician has some experience with indomethacin.
We conclude that at least the specialised neuropaediatricians should be aware of these very rare disorders in childhood, since the diagnostic delay is in most cases up to 10 years end even more (5).
Clinical implications
Typical TACs can occur even in children under the age of 7 years. Data suggest that early onset of TAC is associated with higher frequency of chronic course. The features of the different TACs should be known also in neuropaediatrics.
Footnotes
Declaration of conflicting interest
The authors declare no potential conflicts of interest with respect to the research, authorship and/or publication of this article.
Funding
The authors received no financial support for the research, authorship and/or publication of this article.