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Article

Primary Headache Is Related to Reduced Health-Related Quality of Life in Children with Epilepsy

by
Katharina Schiller
1,2,3,4,*,†,
Veronika Schiller
1,†,
Aline Kortas
1,
Gabriele Unterholzner
1,
Sabine Raffler
5,
Mareike Schimmel
5 and
Markus Rauchenzauner
1,3,4
1
Department of Pediatrics, Hospital Group Kaufbeuren-Ostallgäu, 87600 Kaufbeuren, Germany
2
Department of Neurology and Neurosurgery, Montreal Neurological Hospital and Institute, Montreal, QC H3A2B4, Canada
3
Department of Pediatrics, Medical University Innsbruck, 6020 Innsbruck, Austria
4
Faculty of Medicine, Paracelsus Medical University, 5020 Salzburg, Austria
5
Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Augsburg, 86156 Augsburg, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Healthcare 2024, 12(4), 426; https://doi.org/10.3390/healthcare12040426
Submission received: 14 December 2023 / Revised: 29 January 2024 / Accepted: 4 February 2024 / Published: 7 February 2024

Abstract

:
Headache is a frequent comorbidity in patients with epilepsy. Data are sparse regarding the distribution of headache types in children with epilepsy (CWE). We aimed to assess the prevalence of primary headache types and their influence on health-related quality of life (QoL) in CWE. CWE filled out a validated headache questionnaire to assess migraine (MIG), tension-type headache (TTH), trigeminal–autonomic cephalalgia (TAC), or, if the criteria were not fulfilled, non-classifiable headache (NCH). QoL was measured using both patient and parent versions of a validated questionnaire. Of 119 CWE (59 female; 11.5 ± 3.1 y), headache was found in 46 (38.7%). Sixteen (34.8%) patients showed MIG, 9 (19.6%) patients TTH, and 21 (45.7%) patients described NCH. More girls reported headache (χ2 = 5.4, p = 0.02) when compared to boys. Overall, QoL was reduced in patients with headache from both the patients’ and parents’ points of view (70.8% [39.6; 87.5] vs. 77.0% [46.9; 95.8], p = 0.002; 71,9% [33.3; 87.5] vs. 78,1% [54.2; 95.8], p = 0.003). Headache is common among CWE with MIG as the most prevalent primary headache type and higher rates in female patients. Importantly, patients and their parents perceive a reduced overall QoL when suffering from headache.

1. Introduction

Among the most common comorbidities of patients with epilepsy is headache [1]. Besides a shared common pathophysiology between epilepsy and headache, in particular migraine [2], genetic disposition also seems to play an important role [2,3]. Primary headache types are described as headaches without an apparent underlying cause [4] and the main categories are, according to the International Classification of Headache Disorders (ICHD-3), migraine (MIG), tension-type headache (TTH), trigeminal–autonomic cephalgia (TAC), and neuralgia [5].
MIG is described in adults as unilateral, pulsating headaches of moderate or severe intensity, which can be intensified by physical activity and can occur with or without an aura. For children, these criteria were modified and include bilateral headache, lasting 2 to 72 h, along with nausea and/or vomiting and an additional two of five other associated symptoms (phototopia, phonophobia, difficulty thinking, lightheadedness, fatigue) [6]. The prevalence of MIG in the general pediatric population varies between 5–30% in preschool children and adolescents, and symptoms can vary with the age of the child [7,8,9,10]. Various studies have shown an association between epilepsy and MIG, which share common clinical features [11]. In a pediatric headache center, the risk of epilepsy in children with MIG was 3.2 times higher than in children with TTH [12]. Two antiseizure medications, topiramate and valproic acid, are also approved for MIG prophylaxis [13,14,15,16]. TTH, as the second category of primary headache types, is typically characterized by a bilateral headache which is non-pulsating and a pressing pain with mild–moderate intensity [5]. TTH is frequently found in the general population and a systematic review in children showed a prevalence of 17% [10]. The third category of primary headache types is TAC, which appears unilaterally in the orbital, supraorbital, or temporal region with intense to very intense pain [5]. The prevalence of TAC is very low, affecting roughly 0.1% of people, especially men [17].
Children with epilepsy (CWE) are at risk of showing a reduced overall health-related quality of life (QoL) and reduced family activities or impacted mental health [18,19]. They are at risk of many comorbidities and must also cope with the stress of managing seizures [20]. This burden may also impact social aspects of their lives [21]. There is some evidence that children with episodic MIG and also adults suffering from MIG experience lower QoL than healthy controls [22,23]. Currently, it is unknown whether comorbid headache might lead to a reduction of QoL in children with epilepsy.
Data are sparse regarding the distribution of primary headache types in CWE. Therefore, the goal of the present study was to assess the prevalence of primary headache types (MIG, TTH, and TAC) in CWE, as well as gender differences. Additionally, we aimed to investigate their influence on health-related QoL from both the child’s and parent’s perspectives.

2. Materials and Methods

In this prospective bi-center study, patients with diagnosed epilepsy visiting the seizure outpatient clinic of the Children’s Hospital Kaufbeuren (March 2020–December 2021) and the University Children’s Hospital Augsburg (March 2019–December 2019) were included. Written informed consent was obtained from all patients and parents. This study was performed in accordance with the Declaration of Helsinki and approved by the Research Ethics Board of the Ludwig-Maximilians-University Munich (18–515, 27 November 2018).
The study population consisted of n = 119 children (59 female, 60 male) diagnosed with epilepsy by a pediatric neurologist [24]. Seventy-six patients were included at the Children’s Hospital Kaufbeuren and 43 patients at the University Children’s Hospital Augsburg. Study participants fulfilled the criteria of (i) a documented diagnosis of epilepsy and (ii) age between 7 and 17 years to enable completion of the validated questionnaires. Children had to be able to fill out the questionnaires. Therefore, patients with severe cognitive impairment were not included in this study. Data were obtained during outpatient visits. First, patients were asked if they experienced headaches. If they reported having headaches, they were given the headache questionnaire, the self-developed questionnaire with epilepsy-related and sociological items, and the QoL questionnaire. If patients denied having headaches, they skipped the headache questionnaire and filled out the self-developed questionnaire with epilepsy-related and sociological items as well as the patient version of the QoL questionnaire. For all patients, one or both parents filled out the parent version of the QoL questionnaire.

2.1. Headache Questionnaire

To assess the different headache types, we used a validated questionnaire designed to differentiate between MIG, TTH, and TAC [25] based on the classification criteria of the International Headache Society (ICHD-2) [26]. A fourth category described non-classifiable headache (NCH) if not all criteria for a main headache type were fulfilled. There were three blocks for MIG, TTH, and TAC; the first two blocks for MIG and TTH consisted of seven items respectively, with two additional items to differentiate between MIG with or without aura. TAC was assessed by six items. Each item (e.g., Do you feel a pulsating headache?) had to be answered with ‘yes’ or ‘no’. Following each block, the total days per month with this kind of headache were reported. This allowed for differentiation between chronic headache (15 days or more) and episodic headache (14 days or less). At the end, the following headache types were determined: MIG with aura, MIG without aura, TTH, TAC, and the combinations of MIG + TTH, MIG + TAC, and TTH + TAC. If the criteria for any of these specific headache types were not fulfilled, the headache was described as non-classifiable (NCH).

2.2. Epilepsy-Related and Sociological Data

In a self-developed questionnaire, age, sex, and data regarding epilepsy such as duration of epilepsy and seizure freedom in the last 12 months (yes/no) were assessed. If patients reported having headaches, they were further asked whether the headache occurred together with a seizure (before = preictal/during = ictal/after = postictal). We added items regarding media consumption (television, computer, gaming console: h/week) and whether the child is performing physical activity (sports: yes/no; if yes: h/week).

2.3. Quality of Life Questionnaire

To assess health-related QoL, we administered the questionnaire ‘Kinder Lebensqualität Fragebogen’ (KINDL-R) measuring QoL in children and adolescents between 7–17 years [27,28]. Additionally, the parent’s version was filled out by the accompanying mother, father, or both parents. This questionnaire consisted of 24 items measuring the average feelings and experiences during the previous week using a five-point Likert scale (e.g., during the past week, I felt strong and full of energy; 1 = never to 5 = always). A total score and the following six subscales could be calculated: physical and emotional wellbeing, self-esteem, family, friends, and school. Standardized values are reported on a scale from 0 to 100 with 100 representing the maximum QoL.

2.4. Statistics

Data were tested for normality using the Kolmogorov–Smirnov test and are reported as absolute numbers and percentages in parentheses. Due to non-normally distributed data, groups were compared using the Mann–Whitney U-test. Contingency tables and Pearson’s Chi-squared test (χ2-test) were computed where applicable. A p-value ≤ 0.05 was considered statistically significant. Statistical analyses were performed with the Statistical Package for Social Sciences for Mac (SPSS Inc., Chicago, IL, USA, version 28.0).

3. Results

In total, 119 children with diagnosed epilepsy (59 female; 11.5 ± 3.1 years old) were included in this study. Duration of epilepsy was, at the time of study inclusion, 3.9 ± 3.5 years. Overall, 39 patients (32.8%) had focal, 56 patients (47.0%) generalized, 11 combined focal and generalized (9.3%), and 13 patients (10.9%) were classified with unknown epilepsy. Ninety-five patients (79.8%) had genetic, twelve patients (10.1%) structural, and twelve patients (10.1%) unknown etiology. Within the whole study population, 63 patients (52.9%) were under antiseizure medication monotherapy, 29 (24.4%) were undergoing polytherapy, and 27 (22.7%) had been given no medication at the time of study inclusion.

3.1. Distribution of Headache

Out of 119 epilepsy patients, 46 patients (38.7%) reported suffering from headache. Baseline characteristics are presented in Table 1. Among the 46 patients with headache, 16 (34.8%) fulfilled the criteria for MIG, of which 9 had MIG without aura and 7 MIG with aura. A total of 9 (19.6%) patients reported TTH and the headache of 21 (45.7%) patients was categorized as non-classifiable (NCH) (Figure 1). No patients reported TAC or any combination of primary headache types. Altogether, headache was classified as chronic (≥15 days per month) in two (4.3%) patients, with one reporting chronic MIG without aura and one reporting chronic MIG with aura.

3.2. Headache in Relation to Epilepsy Type

Of the 46 patients reporting headache, 13 patients (28.2%) had focal epilepsy, 24 (52.1%) had generalized epilepsy, 5 (10.9%) had combined focal and generalized epilepsy, and 4 (8.7%) had unknown epilepsy. The distribution of the primary headache types in relation to the type of epilepsy is depicted in Figure 2. The association between primary headache type and type of epilepsy was significant (χ2 = 14.3, p = 0.027). Patients with focal epilepsy mostly reported MIG (n = 7 out of 13) whereas patients with generalized epilepsy most often reported NCH (n = 13 out of 24).

3.3. Headache within Female and Male Patients

Female patients had a higher proportion of headache than male patients. A total of 29 of 59 (49.2%) females and 17 of 60 (28.3%) males experienced headache (Figure 3a). This difference was statistically significant (χ2 = 5.4, p = 0.02).
Of the 29 female patients reporting headaches, 11 (37.4%) showed MIG, 7 without aura and 4 with aura. A total of 8 (27.6%) patients reported TTH and 10 (34.5%) NCH. Of 17 male patients with headache, 5 (29.4%) had MIG, 2 without aura and 3 with aura. Only 1 (5.9%) patient reported TTH whereas 11 (64.7%) described NCH. There was no significant difference between female and male patients regarding the distribution of different headache types (χ2 = 4.9; p = 0.089) (Figure 3b). The two patients reporting chronic MIG were male patients whereas no female patients reported chronic headache (≥15 days per month or more).

3.4. Seizure-Associated Headache

Out of 46 children with headache, 22 (47.8%) described experiencing seizure-associated headaches. Isolated postictal headache was the most frequently reported seizure-associated headache; this was reported by 12 patients and was followed by isolated preictal headache, which was described by 4 patients. No patients reported isolated ictal headache. Five patients had preictal and postictal headache, and one patient reported preictal and ictal headache.

3.5. Headache and Seizure Freedom

In the total study population of 119 CWE, 88 (73.9%) were seizure-free for the last 12 months and 31 (26.1%) were not. The association between headache and seizure freedom was statistically significant (χ2 = 6.6, p = 0.01). There was a higher proportion of children with headache when they were not seizure-free.

3.6. Headache and Sociological Variables

Regarding media consumption, there was no significant difference in patients with headache and without headache (2 h [0; 15] vs. 2 h [0; 10] p = 0.473). Further, there was no significant association between headache and physical activity (yes/no) and no significant difference between patients with and without headache with regards to the duration of physical activity per week (4 h [1; 10] vs. 5 h [1; 20], p = 0.226).

3.7. Quality of Life

Patients with headache reported a reduced total QoL compared to patients without headache (70.8% [39.6; 87.5] vs. 77.6% [46.9; 95.8], p = 0.002, Figure 4). Furthermore, they described a reduced QoL in the subscales physical wellbeing (68.8% [25.0; 93.8] vs. 81.3% [43.8; 100.0], p ≤ 0.001), emotional wellbeing (75.0% [31.3; 100.0] vs. 81.3% [31.3; 100.0], p = 0.038), self-esteem (62.5% [25.0; 100.0] vs. 75.0% [25.0; 100.0], p = 0.043), and school (68.8% [25.0; 93.8] vs. 75.0% [12.5; 100.0], p = 0.004). The subscales family and friend were not significantly different between patients with and without headache (family: p = 0.50; friends: p = 0.36).
Parents rated their children equally in the parent version of the QoL questionnaire and report a reduced overall QoL for patients with headache compared to patients without headache (71.9% [33.3; 87.5] vs. 78.1% [54.2; 95.8], p = 0.003; Figure 5). Similarly, they saw the QoL of their children decrease in the subscales physical wellbeing (62.5% [18.8; 93.8] vs. 84.4% [37.5; 100.0], p = 0.002), emotional wellbeing (75.0% [18.8; 93.8] vs. 81.3% [50.0; 100.0], p = 0.002), and school (68.8% [25.0; 93.8] vs. 75.0% [43.75; 100.0], p = 0.002). The parent-rated subscales self-esteem (p = 0.20), family (p = 0.36), and friends (p = 0.87) were not significantly different between patients with and without headache.

3.8. Quality of Life and Sociological Variables

Media consumption was negatively correlated with overall QoL (r = −0.247, p = 0.012), emotional wellbeing (r = −0.215, p = 0.029), and friends (r = −0.211, p = 0.033) from the patients’ views whereas there was no correlation regarding physical wellbeing (p = 0.084), self-esteem (p = 0.302), family (p = 0.379), and school (p = 0.087). Additionally, the correlation between QoL and media consumption from the parents’ views was not significant (total QoL p = 0.787, physical wellbeing p = 0.442, emotional wellbeing p = 0.719, self-esteem p = 0.371, family p = 0.318, friends p = 0.579, school p = 0.129). From patients’ views, there was a borderline significant enhancement in QoL when they engaged in physical activities, with higher overall QoL (physical activity: 79.2% [39.6; 95.8] vs. no physical activity: 2.9% [39.6; 89.6], p = 0.066) as well as in the subscale friends (75.0% [25.0; 100.0] vs. 71.9% [25.0; 100.0] p = 0.057). From parents’ views, QoL did not differ between both groups (total QoL p = 0.132, physical wellbeing p = 0.131, emotional wellbeing p = 0.337, self-esteem p = 0.819, family p = 0.657, friends p = 0.286, school p = 0.211). The amount of physical activity from the patients’ and parents’ views was not correlated with QoL and the subscales (total QoL p = 0.436, physical wellbeing p = 0.569, emotional wellbeing p = 0.289, self-esteem p = 0.921, family p = 0.786, friends p = 0.568, school p = 0.324).

4. Discussion

In this study, primary headache and QoL were prospectively assessed in a study population of children with diagnosed epilepsy. The main findings indicate that headache is a frequent comorbidity in pediatric epileptic patients with MIG being the most common primary headache type and female patients being more often affected. Further, headache not only reduces the health-related QoL of CWE but also impacts several subscales such as physical wellbeing, emotional wellbeing, self-esteem, and school.
In our study population, headache was a common comorbidity among epilepsy patients with more than one-third of children indicating headaches, which is in line with previous studies [29]. Approximately one-third of children with headaches reported having MIG, which is slightly higher than the one-fourth reported by Kelley et al. [30] and lower than the 43.5% found in Yamane et al. [31]. With regards to the whole study population, 13% of CWE showed MIG which is greater than what was described in a meta-analysis involving the general pediatric population [10]. The higher frequency of MIG in epileptic patients may be explained by shared pathophysiology and genetic disposition [11]. Studies have suggested that the underlying pathophysiology of MIG and epilepsy might be explained by cortical hyperexcitability [32]. There is further the possibility of a genetic link between epilepsy and MIG which could explain the shared pathophysiology [33]. Due to shared clinical symptoms, MIG attacks and epileptic seizures might be confounded, especially in children [11]. According to ICHD-3 [5], an epileptic seizure preceded by a MIG attack is classified as ‘migralepsy’. This is a rare event seen in patients with MIG with aura, which is not included in the criteria for epileptic seizures by the International League Against Epilepsy [34]. Only a very small subset of the patients in this study indicated chronic MIG. The prevalence of MIG is higher during adolescence than during childhood and was also reported to have increased during the coronavirus disease (COVID-19) pandemic [35]. This may also contribute to the high prevalence of MIG in our study cohort.
TTH was less frequent than MIG, with every fifth child experiencing headaches indicating TTH. Findings in adult patients with epilepsy have showed that MIG and TTH might be the most frequent primary headache types with a similar prevalence of around 33% [29,36]. The lower incidence of TTH in children and a high prevalence of NCH in our study population might suggest that part of the NCH in younger age groups may develop into a more defined primary headache type in adulthood. In the whole study population, no child reported the primary headache type TAC or any combination of primary headache types which we previously found in a small subset of our epileptic adult population [36]. Epidemiological data on less common headache types such as TAC are also lacking in the general pediatric population [10]. The type of epilepsy was further associated with the primary headache type. While focal epilepsy patients reported MIG more frequently, patients with generalized epilepsy reported mostly NCH followed by TTH.
The prevalence of headache was higher in female than male children, with female patients more often reporting MIG and TTH-type headaches. A higher prevalence of girls reporting headaches was also found in the general pediatric population [10]. However, in the context of epilepsy, the results are inconsistent. Some studies have found gender differences, reporting higher numbers in female patients [12,36], while others have found no difference [31]. Chronic headache was rare in our population, reported only by two male patients with chronic MIG. This is comparable to results found in children with chronic MIG who often show previous episodic MIG [7]. While it was previously shown that there is a tendency for girls to develop chronic MIG [7], our findings are in contrast to this pattern. However, this might be due to our smaller sample size.
Seizure-associated headache was frequent in CWE and most children described postictal headache followed by preictal headache. This is in line with previous findings in children as well as adults with epilepsy [37,38,39]. In children with drug-resistant epilepsy, MIG was especially found as postictal headache whereas TTH was more common among children with non-drug-resistant epilepsy [40]. Furthermore, there was an association between seizure freedom and headache with a higher proportion of seizure freedom in the subgroup of children without headache.
Patients with headaches were found to have a reduced QoL in comparison to patients without headaches. This was not only evident from the patients’ perspectives but also from the parents’ views on overall QoL as well as on several other domains such as physical wellbeing, emotional wellbeing, self-esteem, and school. Epilepsy treatment and disease management can be very challenging for patients and their families, and the physiological and psychological burden is high [41,42]. Headache seems to have an additional negative impact on CWE, not only physically and emotionally but also academically. Therefore, it is of importance in everyday practice to recognize headaches as a significant influencing factor in disease management and in the patient’s QoL, and to offer tailored support for children and their families.
Finally, we examined the association between sociological factors, such as media consumption and physical activity of patients and the incidence of headache, as well as QoL. While both factors were not related to the existence of headache, media consumption was negatively correlated with QoL from the patients’ views. Contrarily, physical activity tended to increase QoL. The benefit of physical activity on QoL is also known in the general pediatric population [43]. Reducing media consumption and increasing physical activity could therefore counterbalance the detrimental effect of headache on QoL in CWE.
There are some limitations to our study. Headaches were only assessed once, and the sample size limits the generalizability of the results. However, the data were collected prospectively in two different pediatric neurology clinics. Future studies should take family history of headache into consideration. Additionally, the use of a headache diary over a longer time period may allow for more distinct analysis. This would also allow the more detailed study of headache onset, intensity, and frequency. Further, the patients were followed up in the epilepsy clinic and other diseases might be more easily detected than in a child who is not regularly seen in the hospital [44]. However, the known link between epilepsy and MIG suggests that children with epilepsy experience MIG more often than their peers without epilepsy. Finally, psychiatric disorders such as anxiety or depression, which are also present in children with epilepsy, can have a negative impact on QoL [45]. These factors were not considered in our study so the results should be interpreted with caution.

5. Conclusions

In CWE, headache is an important comorbidity and MIG appears to be the most common primary headache type. Female patients reported comorbid headache more often than male patients. From the patients’ and parents’ views, a reduced QoL was indicated when the child was affected by headaches. This should be taken into consideration when treating CWE as headache seems to impact patients in addition to the burden of epilepsy itself.

Author Contributions

Conceptualization, K.S., M.S. and M.R.; methodology K.S., V.S., A.K., G.U. and M.R.; software, K.S.; validation, A.K., G.U., S.R., M.S. and M.R.; formal analysis, K.S., V.S. and M.R.; investigation, K.S., V.S., A.K., G.U., S.R., M.S. and M.R.; resources, M.S. and M.R.; data curation, K.S., V.S., A.K., G.U., S.R. and M.S.; writing—original draft preparation, K.S. and V.S.; writing—review and editing, M.S. and M.R.; visualization, K.S. and V.S.; supervision, M.S. and M.R.; project administration, K.S., M.S. and M.R. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

This study was conducted in accordance with the Declaration of Helsinki and approved by the Research Ethics Board of the Ludwig-Maximilians-University Munich (18-515, 27 November 2018).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The data presented in this study are available on request from the corresponding author.

Acknowledgments

We thank Alysso Ho for support in checking English.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Keezer, M.R.; Sisodiya, S.M.; Sander, J.W. Comorbidities of epilepsy: Current concepts and future perspectives. Lancet Neurol. 2016, 15, 106–115. [Google Scholar] [CrossRef]
  2. Kim, D.W.; Lee, S.K. Headache and Epilepsy. J. Epilepsy Res. 2017, 7, 7–15. [Google Scholar] [CrossRef]
  3. Papetti, L.; Nicita, F.; Parisi, P.; Spalice, A.; Villa, M.P.; Kasteleijn-Nolst Trenite, D.G. “Headache and epilepsy”—How are they connected? Epilepsy Behav. 2013, 26, 386–393. [Google Scholar] [CrossRef]
  4. Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders: 2nd edition. Cephalalgia 2004, 24, 9–160. [Google Scholar] [CrossRef]
  5. Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 2013, 33, 629–808. [Google Scholar] [CrossRef] [PubMed]
  6. Hershey, A.D.; Winner, P.; Kabbouche, M.A.; Gladstein, J.; Yonker, M.; Lewis, D.; Pearlman, E.; Linder, S.L.; Rothner, A.D.; Powers, S.W. Use of the ICHD-II criteria in the diagnosis of pediatric migraine. Headache 2005, 45, 1288–1297. [Google Scholar] [CrossRef] [PubMed]
  7. Youssef, P.E.; Mack, K.J. Episodic and chronic migraine in children. Dev. Med. Child. Neurol. 2020, 62, 34–41. [Google Scholar] [CrossRef] [PubMed]
  8. Abu-Arefeh, I.; Russell, G. Prevalence of headache and migraine in schoolchildren. Bmj 1994, 309, 765–769. [Google Scholar] [CrossRef] [PubMed]
  9. Aromaa, M.; Sillanpää, M.L.; Rautava, P.; Helenius, H. Childhood headache at school entry: A controlled clinical study. Neurology 1998, 50, 1729–1736. [Google Scholar] [CrossRef] [PubMed]
  10. Onofri, A.; Pensato, U.; Rosignoli, C.; Wells-Gatnik, W.; Stanyer, E.; Ornello, R.; Chen, H.Z.; De Santis, F.; Torrente, A.; Mikulenka, P.; et al. Primary headache epidemiology in children and adolescents: A systematic review and meta-analysis. J. Headache Pain. 2023, 24, 8. [Google Scholar] [CrossRef] [PubMed]
  11. Sowell, M.K.; Youssef, P.E. The Comorbidity of Migraine and Epilepsy in Children and Adolescents. Semin. Pediatr. Neurol. 2016, 23, 83–91. [Google Scholar] [CrossRef]
  12. Toldo, I.; Perissinotto, E.; Menegazzo, F.; Boniver, C.; Sartori, S.; Salviati, L.; Clementi, M.; Montagna, P.; Battistella, P.A. Comorbidity between headache and epilepsy in a pediatric headache center. J. Headache Pain. 2010, 11, 235–240. [Google Scholar] [CrossRef]
  13. Storey, J.R.; Calder, C.S.; Hart, D.E.; Potter, D.L. Topiramate in migraine prevention: A double-blind, placebo-controlled study. Headache 2001, 41, 968–975. [Google Scholar] [CrossRef]
  14. Brandes, J.L.; Saper, J.R.; Diamond, M.; Couch, J.R.; Lewis, D.W.; Schmitt, J.; Neto, W.; Schwabe, S.; Jacobs, D.; Group, M.-S. Topiramate for migraine prevention: A randomized controlled trial. JAMA 2004, 291, 965–973. [Google Scholar] [CrossRef] [PubMed]
  15. Hering, R.; Kuritzky, A. Sodium valproate in the prophylactic treatment of migraine: A double-blind study versus placebo. Cephalalgia 1992, 12, 81–84. [Google Scholar] [CrossRef] [PubMed]
  16. Powers, S.W.; Coffey, C.S.; Chamberlin, L.A.; Ecklund, D.J.; Klingner, E.A.; Yankey, J.W.; Korbee, L.L.; Porter, L.L.; Hershey, A.D. Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine. N. Engl. J. Med. 2017, 376, 115–124. [Google Scholar] [CrossRef] [PubMed]
  17. Wei, D.Y.; Yuan Ong, J.J.; Goadsby, P.J. Cluster Headache: Epidemiology, Pathophysiology, Clinical Features, and Diagnosis. Ann. Indian Acad. Neurol. 2018, 21, S3–S8. [Google Scholar] [CrossRef] [PubMed]
  18. Rozensztrauch, A.; Kołtuniuk, A. The Quality of Life of Children with Epilepsy and the Impact of the Disease on the Family Functioning. Int. J. Environ. Res. Public Health 2022, 19, 2277. [Google Scholar] [CrossRef] [PubMed]
  19. Fayed, N.; Davis, A.M.; Streiner, D.L.; Rosenbaum, P.L.; Cunningham, C.E.; Lach, L.M.; Boyle, M.H.; Ronen, G.M. Children’s perspective of quality of life in epilepsy. Neurology 2015, 84, 1830–1837. [Google Scholar] [CrossRef] [PubMed]
  20. Aaberg, K.M.; Bakken, I.J.; Lossius, M.I.; Lund Søraas, C.; Håberg, S.E.; Stoltenberg, C.; Surén, P.; Chin, R. Comorbidity and Childhood Epilepsy: A Nationwide Registry Study. Pediatrics 2016, 138, e20160921. [Google Scholar] [CrossRef] [PubMed]
  21. Camfield, C.S.; Camfield, P.R. Long-term social outcomes for children with epilepsy. Epilepsia 2007, 48, 3–5. [Google Scholar] [CrossRef] [PubMed]
  22. Genizi, J.; Halevy, A.; Schertz, M.; Osman, K.; Assaf, N.; Segal, I.; Srugo, I.; Kessel, A.; Engel-Yeger, B. Sensory Processing Difficulties Correlate with Disease Severity and Quality of Life among Children with Migraine. Front. Neurol. 2019, 10, 448. [Google Scholar] [CrossRef] [PubMed]
  23. Al Ghadeer, H.A.; AlSalman, S.A.; Albaqshi, F.M.; Alsuliman, S.R.; Alsowailem, F.A.; Albusror, H.A.; AlAbdi, Z.I.; Alwabari, E.M.; Alturaifi, Z.A.; AlHajji, A.M. Quality of Life and Disability among Migraine Patients: A Single-Center Study in AlAhsa, Saudi Arabia. Cureus 2021, 13, e19210. [Google Scholar] [CrossRef] [PubMed]
  24. Zuberi, S.M.; Wirrell, E.; Yozawitz, E.; Wilmshurst, J.M.; Specchio, N.; Riney, K.; Pressler, R.; Auvin, S.; Samia, P.; Hirsch, E.; et al. ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: Position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia 2022, 63, 1349–1397. [Google Scholar] [CrossRef]
  25. Fritsche, G.; Hueppe, M.; Kukava, M.; Dzagnidze, A.; Schuerks, M.; Yoon, M.S.; Diener, H.C.; Katsarava, Z. Validation of a german language questionnaire for screening for migraine, tension-type headache, and trigeminal autonomic cephalgias. Headache 2007, 47, 546–551. [Google Scholar] [CrossRef]
  26. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2018, 38, 1–211. [Google Scholar] [CrossRef]
  27. Ravens-Sieberer, U.; Bullinger, M. Assessing health-related quality of life in chronically ill children with the German KINDL: First psychometric and content analytical results. Qual. Life Res. 1998, 7, 399–407. [Google Scholar] [CrossRef]
  28. Bullinger, M.; Brutt, A.L.; Erhart, M.; Ravens-Sieberer, U.; Group, B.S. Psychometric properties of the KINDL-R questionnaire: Results of the BELLA study. Eur. Child. Adolesc. Psychiatry 2008, 17, 125–132. [Google Scholar] [CrossRef]
  29. Duko, B.; Ayalew, M.; Toma, A. The epidemiology of headaches among patients with epilepsy: A systematic review and meta-analysis. J. Headache Pain 2020, 21, 3. [Google Scholar] [CrossRef] [PubMed]
  30. Kelley, S.A.; Hartman, A.L.; Kossoff, E.H. Comorbidity of migraine in children presenting with epilepsy to a tertiary care center. Neurology 2012, 79, 468–473. [Google Scholar] [CrossRef] [PubMed]
  31. Yamane, L.E.; Montenegro, M.A.; Guerreiro, M.M. Comorbidity headache and epilepsy in childhood. Neuropediatrics 2004, 35, 99–102. [Google Scholar] [CrossRef] [PubMed]
  32. Bianchin, M.M.; Londero, R.G.; Lima, J.E.; Bigal, M.E. Migraine and epilepsy: A focus on overlapping clinical, pathophysiological, molecular, and therapeutic aspects. Curr. Pain. Headache Rep. 2010, 14, 276–283. [Google Scholar] [CrossRef] [PubMed]
  33. Haan, J.; van den Maagdenberg, A.M.; Brouwer, O.F.; Ferrari, M.D. Migraine and epilepsy: Genetically linked? Expert Rev. Neurother. 2008, 8, 1307–1311. [Google Scholar] [CrossRef] [PubMed]
  34. Scheffer, I.E.; Berkovic, S.; Capovilla, G.; Connolly, M.B.; French, J.; Guilhoto, L.; Hirsch, E.; Jain, S.; Mathern, G.W.; Moshé, S.L.; et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017, 58, 512–521. [Google Scholar] [CrossRef] [PubMed]
  35. Katsuki, M.; Matsumori, Y.; Kawahara, J.; Yamagishi, C.; Koh, A.; Kawamura, S.; Kashiwagi, K.; Kito, T.; Oguri, M.; Mizuno, S.; et al. School-based online survey on chronic headache, migraine, and medication-overuse headache prevalence among children and adolescents in Japanese one city—Itoigawa Benizuwaigani study. Clin. Neurol. Neurosurg. 2023, 226, 107610. [Google Scholar] [CrossRef] [PubMed]
  36. Schiller, K.; Rauchenzauner, M.; Avidgor, T.; Hannan, S.; Lorenzen, C.; Kaml, M.; Walser, G.; Unterberger, I.; Filippi, V.; Broessner, G.; et al. Primary headache types in adult epilepsy patients. Eur. J. Med. Res. 2023, 28, 49. [Google Scholar] [CrossRef] [PubMed]
  37. Verrotti, A.; Coppola, G.; Spalice, A.; Di Fonzo, A.; Bruschi, R.; Tozzi, E.; Iannetti, P.; Villa, M.P.; Parisi, P. Peri-ictal and inter-ictal headache in children and adolescents with idiopathic epilepsy: A multicenter cross-sectional study. Childs Nerv. Syst. 2011, 27, 1419–1423. [Google Scholar] [CrossRef]
  38. Leniger, T.; Isbruch, K.; von den Driesch, S.; Diener, H.C.; Hufnagel, A. Seizure-associated headache in epilepsy. Epilepsia 2001, 42, 1176–1179. [Google Scholar] [CrossRef]
  39. Yankovsky, A.E.; Andermann, F.; Bernasconi, A. Characteristics of headache associated with intractable partial epilepsy. Epilepsia 2005, 46, 1241–1245. [Google Scholar] [CrossRef]
  40. Caprara, F.; Letícia, A.; Rissardo, J.P.; Leite, M.T.B.; Silveira, J.O.F.; Jauris, P.G.M.; Arend, J.; Kegler, A.; Royes, F.; Fernando, L.; et al. Characteristics of Post-Ictal Headaches in Patients with Epilepsy: A Longitudinal Study. Seizure 2020, 81, 244–249. [Google Scholar] [CrossRef]
  41. Theodore, W.H.; Spencer, S.S.; Wiebe, S.; Langfitt, J.T.; Ali, A.; Shafer, P.O.; Berg, A.T.; Vickrey, B.G. Epilepsy in North America: A report prepared under the auspices of the global campaign against epilepsy, the International Bureau for Epilepsy, the International League Against Epilepsy, and the World Health Organization. Epilepsia 2006, 47, 1700–1722. [Google Scholar] [CrossRef]
  42. Vanstraten, A.F.; Ng, Y.T. What is the worst part about having epilepsy? A children’s and parents’ perspective. Pediatr. Neurol. 2012, 47, 431–435. [Google Scholar] [CrossRef] [PubMed]
  43. Moeijes, J.; van Busschbach, J.T.; Bosscher, R.J.; Twisk, J.W.R. Sports participation and health-related quality of life: A longitudinal observational study in children. Qual. Life Res. 2019, 28, 2453–2469. [Google Scholar] [CrossRef] [PubMed]
  44. Berkson, J. Limitations of the application of fourfold table analysis to hospital data. Biometrics 1946, 2, 47–53. [Google Scholar] [CrossRef] [PubMed]
  45. Cianchetti, C.; Bianchi, E.; Guerrini, R.; Baglietto, M.G.; Briguglio, M.; Cappelletti, S.; Casellato, S.; Crichiutti, G.; Lualdi, R.; Margari, L.; et al. Symptoms of anxiety and depression and family’s quality of life in children and adolescents with epilepsy. Epilepsy Behav. 2018, 79, 146–153. [Google Scholar] [CrossRef]
Figure 1. Flowchart presenting headache distribution (MIG = migraine, TTH = tension-type headache, NCH = non-classifiable headache).
Figure 1. Flowchart presenting headache distribution (MIG = migraine, TTH = tension-type headache, NCH = non-classifiable headache).
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Figure 2. Primary headache type in relation to different epilepsy types.
Figure 2. Primary headache type in relation to different epilepsy types.
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Figure 3. (a) Number of female and male patients with and without headache; (b) Distribution of primary headache types among female and male patients. Significant results (p < 0.05) are indicated by a star.
Figure 3. (a) Number of female and male patients with and without headache; (b) Distribution of primary headache types among female and male patients. Significant results (p < 0.05) are indicated by a star.
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Figure 4. QoL from the patient’s view in terms of overall QoL and six subscales. Significant reductions were seen in QoL in patients with headache in terms of overall QoL, physiological wellbeing, emotional wellbeing, self-esteem, and school. Significant results (p < 0.05) are indicated by a star.
Figure 4. QoL from the patient’s view in terms of overall QoL and six subscales. Significant reductions were seen in QoL in patients with headache in terms of overall QoL, physiological wellbeing, emotional wellbeing, self-esteem, and school. Significant results (p < 0.05) are indicated by a star.
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Figure 5. QoL from the parent’s view in terms of overall QoL and six subscales. Significant reductions were seen in QoL in patients with headache in terms of overall QoL, physiological wellbeing, emotional wellbeing, and school. Significant results (p < 0.05) are indicated by a star.
Figure 5. QoL from the parent’s view in terms of overall QoL and six subscales. Significant reductions were seen in QoL in patients with headache in terms of overall QoL, physiological wellbeing, emotional wellbeing, and school. Significant results (p < 0.05) are indicated by a star.
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Table 1. Baseline characteristics of the whole study cohort and patients with primary headache.
Table 1. Baseline characteristics of the whole study cohort and patients with primary headache.
All Patients with EpilepsyPatients with Epilepsy and Primary Headache
N=11946
Age, y (mean ± SD)11.5 ± 3.111.3 ± 3.2
Sex (female/male)59/6029/17
Epilepsy duration, y (mean ± SD)3.9 ± 3.54.6 ± 4.3
Types of epilepsy, n (%)
  Focal39 (32.8%)13 (28.3%)
  Generalized56 (47.0%)24 (52.1%)
  Combined focal and generalized11 (9.3%)5 (10.9%)
  Unknown13 (10.9%)4 (8.7%)
Etiology
  Genetic95 (79.8%)35 (76.1%)
  Structural12 (10.1%)6 (13.0%)
  Unknown12 (10.1%)5 (10.9%)
Antiseizure medication, n (%)
  Monotherapy63 (52.9%)24 (52.2%)
  Polytherapy29 (24.4%)14 (30.4%)
  No medication27 (22.7%)8 (17.4%)
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MDPI and ACS Style

Schiller, K.; Schiller, V.; Kortas, A.; Unterholzner, G.; Raffler, S.; Schimmel, M.; Rauchenzauner, M. Primary Headache Is Related to Reduced Health-Related Quality of Life in Children with Epilepsy. Healthcare 2024, 12, 426. https://doi.org/10.3390/healthcare12040426

AMA Style

Schiller K, Schiller V, Kortas A, Unterholzner G, Raffler S, Schimmel M, Rauchenzauner M. Primary Headache Is Related to Reduced Health-Related Quality of Life in Children with Epilepsy. Healthcare. 2024; 12(4):426. https://doi.org/10.3390/healthcare12040426

Chicago/Turabian Style

Schiller, Katharina, Veronika Schiller, Aline Kortas, Gabriele Unterholzner, Sabine Raffler, Mareike Schimmel, and Markus Rauchenzauner. 2024. "Primary Headache Is Related to Reduced Health-Related Quality of Life in Children with Epilepsy" Healthcare 12, no. 4: 426. https://doi.org/10.3390/healthcare12040426

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