SUNCT/SUNA in children and adolescents: Application of ICHD-3 criteria and treatment response: Case series of 13 SUNCT/SUNA pediatric cases

Abstract

Introduction

Trigeminal autonomic cephalalgias (TACs) are characterized by paroxysmal attacks of unilateral primary headaches associated with ipsilateral craniofacial autonomic symptoms. In this pediatric case series, 13 cases of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)/short-lasting unilateral neuralgiform headache with autonomic symptoms (SUNA), including children ages 3–18 years, are discussed. This paper reviews the application of International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria especially in children presenting with SUNCT or SUNA. This is the largest pediatric case series of SUNCT/SUNA reported in the literature.

Background

Trigeminal autonomic cephalalgias are rare in children and adolescents, with SUNCT/SUNA having the least reported cases. We will discuss the application of ICHD-3 criteria to diagnose SUNCT/SUNA in children and review overlapping cases and their response to different treatment options including indomethacin, which is typically reserved for specific subtypes of TACs; for example, paroxysmal hemicrania.

Conclusion

This case series presents a unique opportunity to aid in the diagnosis and treatment of similar pediatric cases in the future. It helps us to broaden the ICHD-3 criteria to diagnose and treat different overlapping trigeminal autonomic cephalalgia cases in children.

Introduction

It is generally believed that the incidence of trigeminal autonomic cephalalgias (TACs) is lower in children when compared to adults with cluster headaches, comprising most adult cases. Recently, the VAGA study suggested an almost similar incidence of TACs in adolescents when compared with adult patients (1). The overall grouping of the TACs is based on the commonality of autonomic features and pain in the trigeminal distribution. with many commonalities between the different subtypes of TACs. The rare forms of TACs, including Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing (SUNCT) and Short-lasting Unilateral Neuralgiform headache with Autonomic symptoms (SUNA), are closely related. According to ICHD-3 criteria, SUNCT and SUNA are differentiated from other forms of TAC by their time criterion (1 sec to 10 min) with unilateral autonomic trigeminal distribution of symptoms. SUNCT was first added to the International Classification of Headache Disorders (ICHD) criteria in the 2nd edition, while SUNA was added in the 3rd edition, thus making these headache disorders relatively newly recognized. The features of SUNCT and SUNA overlap with other TACs, particularly paroxysmal hemicrania, in which symptoms may last from 2–30 min and with absolute response to indomethacin (2). This indomethacin responsiveness is used as a diagnostic distinction. This distinction lacks critical biomarkers to address the separation of indomethacin responders versus non-responders and is largely clinically and anecdotally driven. In children and adolescents, both the clinical features and responsiveness may differ from adults, as the brain is developing, and thus represent a more “pure” or evolving phenotype where refractoriness to treatment has yet to develop (3). Additionally, it may be difficult to ascertain the strict duration criterion that differentiates SUNCT and SUNA from other indomethacin-responsive headaches, as has been suggested for other primary headache disorders (i.e. duration of headaches is shorter in children and adolescents). This presents a treatment barrier as there are no clear guidelines for early treatment, treatment trajectory changes, and treatment of overlapping cases of TACs. This case series is unique as it highlights the importance of overlapping cases of SUNCT and SUNA with other TACs, particularly paroxysmal hemicrania.

Patient information

We used our database to identify patients presenting to the Headache Center at Cincinnati Children’s Hospital Medical Center between 2007, when SUNCT was accepted into the ICHD, and to the latest available data in 2020. A total of 18 pediatric cases were identified who held a diagnosis of SUNCT or SUNA, with 13 of those patients fulfilling criteria as defined by the ICHD-3. Nine of the 13 were also diagnosed with migraine at presentation and all were found to have a family history of migraine. Most children reported moderate to severe disability on the Pediatric Migraine Disability Assessment Test (PedMIDAS) at the time of initial presentation. All patients were given a diagnosis of SUNCT or SUNA during their first office visit. This is an interesting observation, as adult epidemiological studies have shown that there is an average of 7 years’ delay in the diagnosis of TACs after seeing a neurologist (4).

Clinical findings

All 13 children presented with unilateral acute stabs of head pain with ipsilateral autonomic symptoms within the trigeminal distribution. The mean age at presentation was 10 years (range 3–18 years) with almost equal male (46%) and female (54%) distribution. Tearing and conjunctival injection were the most prominent symptoms (92%) and each child reported more than 20 attacks lasting 1 sec to 10 min for > 3 months, hence fulfilling ICHD-3 criteria of SUNCT or SUNA. Two patients (15%) also fulfilled the time duration criteria extending into the paroxysmal hemicrania range for diagnosis (2–30 min). Five children had abnormal MRI imaging; however, it is not clear if abnormal imaging was related to TAC. One patient had abnormal MRI findings diagnostic for multiple sclerosis. This patient, interestingly, presented with TAC defining headaches as the only presenting symptom. One patient had ataxia on exam. This patient had hydrocephalus secondary to symptomatic cavum septum pellucidum s/p fenestration and it was not clear whether hydrocephalus resulted in ataxia or there was any other etiology for ataxia. Most of these cases (97%) presented with symptoms lateralizing to the right. Clinical and MRI findings are further described in Table 1.

Table 1.

Clinical presentation of cases.

Cases	Age	Duration (sec) Frequency	Site/autonomic symptom	Indomethacin/ response (+/−) and f/u	Other Tx response	Exam	Imaging	Migraine	Other Dx	PedMIDAS
1	3	10–120 30/month	Right/tearing, eyelid edema	Y/+ (2 years) f/u for 2 years after stopping	NA	Normal	Chiari 1 s/p surgical decompression	No	Chiari 1	NA
2	3	60–180 15/month	Right/tearing, injection	N/NA	Cyproheptadine, no response, lost f/u	Normal	Normal	No	NA	NA
3	5	60–1200 30/month	Right/tearing, injection	Y/+(4 years) three failed weans over 4 years	NA	Normal	Normal	No	NA	120
4	9	10–600 30/month	Left/facial swelling	N/NA	Amitriptyline, no response, lost f/u	Normal	Normal	Yes	Hypermobility	72
5	9	5–10 30/month	Right/tearing, eyelid edema	Y/−No response f/u 10 years	Oxygen, excellent response	Normal	Normal	Yes	Hypermobility	9
6	11	5–10 30/month	Right/tearing, injection	Y/+ (2 years) lost f/u	NA	Normal	Gliosis	No	Anxiety	24
7	11	120–900 20/month	Right/tearing, injection	Y/−No response f/u for 7 years	Oxygen, good response divalproex and amitriptyline, poor response	Ataxia	Cavum septum pellucidum, s/p fenestration	Yes	Cavum septum pellucidum/ataxia	31
8	13	10–300 4/month	Right/facial swelling, tearing	N/NA	Topiramate good response, weaned in 2 years	Normal	Normal	Yes	Anxiety	10
9	13	300–600 15/month	Right/eyelid edema, injection, tearing	N/NA	N/NA, lost f/u	Normal	Left cerebellar hemangioma	No	Hypermobility	24
10	13	30–100 30/month	Right/facial flush and tearing	Y/+ (3 years) 2 failed weans	NA	Normal	Normal	Yes	NA	28
11	16	20–300 30/day	Left/eyelid edema, tearing, facial swelling	Y/+ (2 years) Then stopped	Botox for later chronic migraine	Normal	Low lying cerebellar tonsils	Yes	NA	190
12	18	60–120 8/month	Left/tearing, facial swelling	N/NA	NA	Normal	Multifocal demyelinating lesions	Yes	MS	100
13	18	20–1200 30/month	Right/facial swelling, eyelid edema, tearing	N/NA	Naproxen+ Topiramate, lost f/u	Normal	Normal	Yes	EDS	NA

Tx: Treatment; PedMIDAS: Pediatric Migraine Disability Assessment Test; NA: Not applicable; MS: Multiple Sclerosis; EDS: Ehlers-Danlos syndrome; S/P: Status Post; F/U: Follow up; Y: Yes indomethacin; N: No indomethacin; Sec: Seconds.

Therapeutic intervention

There is no general consensus or guidelines available to treat SUNCT and SUNA headaches in children and adolescents due to lack of evidence and rarity of cases. Historically, indomethacin is reserved for paroxysmal hemicrania, which also aids in its diagnosis. In our Headache Center, we offer and explain different treatment options to the patients and their parents and allow them to make an informed decision for treatment. In these cases, all options, including indomethacin, were discussed and seven families elected to trial indomethacin (1 mg/kg with max 150 mg/day). Other options trialed included oxygen, divalproex, topiramate, amitriptyline and cyproheptadine. Except for the single case diagnosed with multiple sclerosis, the other children with abnormal MRI findings also received a trial of indomethacin.

Follow-up and outcomes

Overall, seven out of 13 cases were offered indomethacin; five cases had resolution of attacks with the average time to response of 7 days. The remaining two children, who were found to be non-responders, were offered oxygen with resolution of their attacks. One of the cases fulfilling the time duration criteria for both SUNCT or SUNA and paroxysmal hemicrania had excellent response to indomethacin and had three failed weaning attempts. On average, patients remained on indomethacin for 2 years. One patient had resolution of symptoms with indomethacin and remained headache free for 2 years, but later developed chronic migraine. This patient was later treated with onabotulinumtoxin-A with an excellent response. All indomethacin users had first phone follow-up after 7 days and then routine follow up visits at 8–12 week intervals. Patients with additional diagnosis of migraine were offered usual migraine treatments as well (particularly if they declined an indomethacin trial). These treatments (amitriptyline/topiramate etc., see Table 1) may improve headaches in some cases, so it is not clear whether it was overall improvement in their migraine symptoms or TAC.

Discussion

According to the ICHD-3, SUNCT or SUNA headaches are a subtype of the TAC and are defined as “attacks of moderate or severe, strictly unilateral head pain lasting from seconds to 10 minutes, occurring at least once a day (few cases may have less frequent attacks) and are usually associated with prominent lacrimation and redness of the ipsilateral eye”. Due to limited pediatric cases of TACs and even fewer fulfilling criteria for SUNCT or SUNA, there is a lack of evidence regarding the appropriate treatment approach to these patients.

In children and adolescents, it may be difficult to adapt the diagnostic criteria with strict temporal relation, hence few cases may benefit from broader definition criteria and may be offered indomethacin, a treatment which is usually reserved for slightly longer duration cases otherwise presenting with similar ipsilateral trigeminal distribution autonomic findings.

Another important differential is trigeminal neuralgia, and this may be difficult to distinguish clinically. Most of our cases had normal or unrelated neuroimaging. Normal neuroimaging or lack of secondary causes are not included in the diagnostic criteria, but due to rarity of cases and concern of posterior fossa lesions mimicking SUNCT or SUNA headaches, good modality neuroimaging (MRI brain) is recommended while making a diagnosis (5).

Early treatments including indomethacin, oxygen and other preventives may decrease the frequency of attacks and improve the quality of life.

Conclusion

TACs may have higher prevalence than perceived in children and should be included in the differential diagnosis when children with headache present with strict unilateral autonomic symptoms. We also suggest that indomethacin and oxygen should not be reserved only for cases historically considered “responders” but may be trialed in overlapping cases. The ICHD-3 temporal criterion for TACs helps us to differentiate different subtypes of TACs but there may be some overlap in pediatric cases that provides an opportunity to broaden the differential.

Clinical implications

Early treatments including indomethacin, oxygen, and other preventives may decrease the frequency of attacks and improve the quality of life.

In children and adolescents, it may be difficult to adapt the diagnostic criteria with strict temporal relation, hence few cases may benefit from broader definition criteria and may be offered indomethacin, a treatment that is usually reserved for slightly longer duration cases otherwise presenting with similar ipsilateral trigeminal distribution autonomic findings.