Abstract
Background
No study dedicated to postdrome symptoms of migraine attacks is available in children and adolescents.
Objective
To study the resolution phase of the migraine attack in children and adolescents.
Methods
100 children and adolescents with ICHD-3 beta migraine without and/or with typical aura were included. Each patient, and one of her/his parents, were interviewed by phone about the postdrome phrase of their last six months’ migraine attacks. They were specifically instructed to distinguish symptoms that had begun before and went on after migraine headache cessation (referred to as persistent symptoms), and symptoms whose onset was strictly after headache cessation (referred to as true postdromes).
Results
91% of patients reported persistent symptoms, with a mean of 2.9 and a median of 2; asthenia, cognitive difficulties, pallor, cognitive slowing, anorexia, somnolence, and nausea were the most frequently reported. They lasted less than 12 h in 71% of patients. True postdromes were reported by 82% of patients, with a mean of 2.6 and a median of 2; thirst, somnolence, visual disturbances, food craving, paraesthesias, and ocular pain being the most frequently reported. They lasted less than 12 h in 94% of patients.
Conclusions
This study showed that children and adolescents with migraine had both frequent persistent symptoms and true postdromes. Both were notably different from those reported in adults.
Keywords
Introduction
Migraine affects about one in 12 children (1,2). Since the pioneering study by Bille, the clinical presentation of pediatric migraine has received much attention (3). Among the four phases of the migraine attack with their specific symptoms, the last one, i.e. postdrome, was only recently (4,5) and probably less well studied. To our knowledge, postdrome has not been studied so far in the pediatric population, whereas several studies dedicated to premonitory symptoms and/or triggers are available, including our studies in children and adolescents (6,7). In the wake of these studies, we contemplated the opportunity of studying postdrome as well, but were faced with unexpected difficulties. First, a great many attacks terminated with the child falling asleep. The attempt to question them upon awakening about the resolution phase of their attack gave unreliable results, which led us to choose to consider interviewing them about the last semester’s attacks retrospectively. Second, the after phase of the headache comprised two groups of symptoms: Symptoms that had begun before and went on after migraine headache cessation, and symptoms whose onset was strictly after headache cessation. As the medical literature does not bring clear answers on this point, we decided to distinguish both sets of symptoms separately. Both patient and parents were specially instructed to distinguish separately persistent symptoms (PS) that had begun before the headache had resolved and were persistent after migraine headache cessation, and true postdromes (TPD) that had begun after the headache had resolved.
Patients and methods
The study population consisted of children and adolescents randomly selected from the database of one of the authors (JCC). Eligible subjects were children and adolescents (<18 years of age) who fulfilled the ICHD-3 beta criteria for paediatric migraine without aura (MO) and/or with typical aura (MA) at the time of study (i.e. ICHD-3 beta 1.1 and/or 1.2.1) (8), who experienced migraine attacks for at least six months before study entry, had had less than 15 headache days per month during last three months and were not on preventive drugs for migraine or any other regular medications that could confound the study.
Enrollment started in May 2015 and ended in October 2015. We decided to contact patients included in the database during the previous two years. Patients and/or their parents were contacted by phone to present and explain the objective and the design of the study. They were invited to participate in the study. Those who accepted were interviewed by phone by the same physician (OM). The patient and one of his/her parents were interviewed together. The phases of migraine were explained to both, including the concept of postdrome. The first part of the questionnaire addressed demographic factors (age, gender) and presented migraine characteristics. Migraine-related variables were: Migraine subtype (MO and/or MA according to the ICHD-3 beta criteria), and mean attack frequency per month in the last six months.
The second part of the questionnaire addressed a pre-determined list of 31 resolution phase symptoms based on reports in the adult literature. This pre-determined list of symptoms included abdominal pain, anorexia, anxiety, asthenia, cognitive difficulties, cognitive slowing, concentration difficulties, euphoria, food craving, general malaise, head pain, hearing disturbance, irritability, nausea, neck pain, ocular pain, odor sensitivity, pallor, paresthesia, runny nose, sadness, somnolence, taste disturbance, thirst, tremor, vertigo, visual disturbance, voice change, vomiting, weakness, and yawning. The Appendix presents the five questions patients were asked to answer concerning the attacks occurring during the last six months. It was possible to add additional symptoms not included in this list and answer the questions as well. They could also state that they felt the attack had no TPD/PS.
All the subjects and their guardians provided written consent for their participation in the study, which was approved by the Research Ethics Committee of the French Pediatrics Society – Comité d’éthique de la recherche de la Société Française de Pédiatrie. An individual identifier was given to each participant and the data were anonymized.
Statistical analysis
Qualitative variables are expressed as frequency (percentage) and quantitative variables as median (range) (normality of distribution was checked graphically and by using the Shapiro–Wilk test). We compared the number of PS and TPD between boys and girls using Mann-Whitney U tests. The comparison between the migraine subtypes was made using Kruskall-Wallis tests. The duration was compared between boys and girls using a Cochran Armitage trend test. The association between duration and age was checked using a Spearman’s rank correlation coefficient. Statistical testing was done at the two-tailed α level of 0.05. Data were analysed using the SAS software package, release 9.4 (SAS Institute, Cary, NC).
Results
Of the 120 subjects fulfilling the inclusion criteria contacted by phone, 100 agreed to answer the questionnaire (83%, 49 boys). The characteristics of the non-participants did not statistically differ from those of the participants. The subjects’ age ranged from 4 to 17 years old (mean: 10.5 years). Sixty six patients had MO (66%), 26 MA (26%), and 8 patients both MO and MA (8%). Number of attacks per month was <2 in 33 patients (33%), 2– <4 in 50 patients (50%), 5– <7 in seven patients (7%), 7– <9 in five patients (5%), and 9– <15 in five patients (5%). The interviewed parent was mostly the mother (n = 95), and the father in the five remaining cases.
Twenty had no PS (three boys). Asthenia was the most frequently reported PS (49%), followed by cognitive difficulties (42%), pallor (38%), cognitive slowing (28%), anorexia (26%) sleepiness (22%), and nausea (22%) (Figure 1). The median number of PS was 2 (0–10) in patients with MO, 3 (0–8) in patients with MA, and 3 (0–5) in patients with both MO and MA (p = 0.60). All patients (and parents) were able to give the time of onset and frequency for each single symptom with not one missing answer. But not all patients (and parents) were able to give the duration (if applicable). Eighty patients/parents were able to specify PS duration, accounting for 291 PS (Table 1). When considering both PS duration and attack frequency, 36 of the 80 patients with PS (45.0%) reported both PS duration under 6 h and frequency comprised between ≥2/3 – < 1 of attacks.
Numerical distribution of persistent symptoms (PS) and true postdromes (TPD). Duration and frequency of persistent symptoms/true postdromes. PS: persistent symptoms, TPD: true postdromes PS +/PS− : patients with/without PS, TPD ±: patients with/without TPD Figures refer to number of PS Figures refer to number of TPD
Eighteen had no TPD (6 boys). Thirst was the most frequently reported TPD (36%), followed by sleepiness (36%), visual disturbances (25%) food craving (19%), paraesthesia (16%) and ocular pain (16%) (Figure 1). The median number of TPD was 2 (0–11) in patients with MO, 3 (0–9) in patients with MA, and 1 (0–3) in patients with both MO and MA (p = 0.03). Time of onset of TPD was <30 min after migraine headache cessation in 95% of patients. Eighty-two patients/parents were able to specify TPD duration, accounting for 257 TPD (Table 1). When considering both TPD duration and attack frequency, 54 of the 82 patients with TPD (65.9%) reported both TPD duration under 3 h and frequency comprised between ≥2/3 – <1 of attacks. When pooling TPD and PS together (n = 548), duration was < 3 hours for 285 TPD and PS (52%), 3 to <6 hours for 83 TPD and PS (15%), 6 to <12 hours for 80 TPD and PS (15%), 12 to <24 hours for 94 TPD and PS (17%) and ≥24 hours for 6 TPD and PS (1%). Respective figures (n, (%)) according to gender were 138 (45) vs. 147 (60) (<3 h), 53 (17) vs. 30 (12) (3 to <6 hours), 49 (16) vs. 31 (13) (6 to <12 hours), 59 (19) vs. 35 (14) (12 to <24 hours), and 6 (2) vs. 0 (0) (≥24 hours) for boys vs. girls, respectively. Mean for pooled data (PS + TPD) was 5.5 ± 3.3 (boys: 6.2 ± 2.6, girls: 4.8 ± 3.8) and median, 5 [range: 0–16] (boys: 6 [0–12], girls: 5 [0–16]. Duration thus was shorter for girls (p < 0.001). There was no correlation between age and duration (r = −0.002, p = 0.97) nor between migraine subtype and duration (p = 0.65).
Discussion
Bearing in mind the distinction that we previously introduced (i.e. PS/TPD), our results show that both postdrome symptoms were frequent in children and adolescents with migraine. Both PS and TPD lasted under 12 h in most patients. Patients with MA had TPD more often than patients with MO or patients with both MO and MA.
In the absence of another pediatric study dedicated to postdrome, we can only compare our results with adult studies, with the additional difficulty of there being no uniform definition of postdrome among studies, particularly when it comes to its onset. For instance, Quintela et al. stated that “‘True’ resolution symptoms were those experienced the day after the headache had started only if they were not present in a questionnaire completed in a pain-free period” (9). For Kelman, “at the initial visit, the phases of migraine were explained to patients, including the concept of postdrome. They were asked whether they experienced postdrome (yes/no)” (10). Finally, Ng-Mak et al. defined “the onset of postdrome as when they no longer experienced the migraine pain” (11). A recent review defines the migraine postdrome as “that constellation of symptoms occurring once the acute headache has settled” (12). For Giffin et al., the postdrome was defined as “the time between headache resolution and feeling completely back to normal” (13). That is why we decided to distinguish TPD and PS separately, according to the convention indicated in the methods section. Of course, these discrepancies limit direct comparisons. In the studies by Blau, Kelman and Quintela, respectively 94%, 68%, and 80% of patients had postdrome (5,9,10). Postdrome duration was longer in adults, with a mean of 18 h (Blau) and 25.2 h (Kelman) (5,9). In one small study (n = 34), the postdrome duration comprised between 30 min and six hours for most symptoms, but could last up to four days for some patients (5). In a recent electronic diary study, 54% of patients had a postdrome duration <6 h and only 7% of patients had a postdrome duration >24 h (13).
The most frequent TPD in this study were thirst, somnolence, visual disturbances, food craving, and paresthesias. They are notably different from those reported in adults. Indeed, further comparison with adult studies is hampered by the use of different definitions for postdrome, which do not match with those we used in this study (i.e. PS/TPD). Another difficulty lies in the use of different terminologies that probably refer to close or similar symptoms (e.g. asthenia vs. fatigue) (12). Bearing this in mind, the most common postdrome symptoms cited in adult studies were asthenia, somnolence, phonophobia, photophobia, unhappiness, and yawning (9), head pain, cognitive difficulties, “hangover”, gastrointestinal symptoms, mood change and weakness (10), nausea, physical weakness (11), tiredness (9,10,13), and concentration difficulties (10,11).
While a majority of women reported postdrome symptoms in the studies by Blau and Kelman (respectively 85.2% and 77.5%), there was no female preponderance in this study, whose sample sex ratio was balanced (51% girls) (5,10). Similarly to adult studies, we found that PS were more frequent in patients with MA only compared to MO only and both MO and MA (9,10). Boys reported more PS than girls (94% vs. 67%, p < 0.001) and had a greater number of PS (mean: 3.0 vs. 2.0, p = 0.003). The duration of PS/TPD was shorter in girls, which, to our knowledge, has not been reported in adults. Girls cited somnolence (76%) more often as a TPD than boys (43%, p = 0.01).
There are limits in our study. It is retrospective; the sample is small and stems from a tertiary unit. More problematic are difficulties related to the aspects of time and memory in children. Time perception is worse in children compared with adults (14). This process is not only based on a clock system but is also influenced by attention, memory, and decisional processes. It is reasonable to think that cognitive disturbances induced by the migraine attack may further make things more difficult. One may nevertheless point out that recording data in the immediate after-attack period would also be fraught with obvious difficulties related to PS and/or TPD such as cognition and/or concentration difficulties, somnolence or even sleep. It is well known that the migraine attack terminates with the child falling asleep in as many as 60% of children (15). One may discuss the general reliability of assessing the onset, two types of duration and the frequency of numerous overlapping symptoms retrospectively over a period of six months in patients with a mean age of 10 years. Nevertheless, the fact that one of the parents was implicated in the questionnaire may add to the strength of the data collection, as shown by our previous study on premonitory symptoms where “face changes” were noticed mostly by the participants’ parents (6).
In conclusion, this study may be viewed as preliminary. Children and adolescents do have frequent persistent symptoms/true postdromes (according to the terminology we previously adopted). The results should be confirmed by a prospective study, using electronic diaries, having solved the difficulty related to attacks ending in sleep, with a larger sample. However, we think that this line of research, by the developmental aspect it introduces, may shed useful light on migraine mechanisms.
Clinical implications
The resolution phase of the migraine attack comprised symptoms that had begun before and went on after migraine headache cessation (here referred to as persistent symptoms), and symptoms whose onset is strictly after headache cessation (here referred to as true postdromes). Most pediatric patients (>80%) had both persistent symptoms (91%) and true postdromes (82%). Asthenia, cognitive difficulties, and pallor were the three most frequently reported PS. Thirst, sleepiness, and visual disturbances were the three most frequently reported TPD. Both persistent symptoms and true postdromes lasted less than 12 h in over two thirds of patients.
Footnotes
Declaration of conflicting interests
The authors declared 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.