Asthma and related allergic disorders including sinusitis are a common problem in children and adolescents. Approximately, 9 % of children and adolescents have asthma, and this increases to 32 % for any allergic condition [7]. Migraine itself has a neuroinflammatory component, and it could be expected that in patients with immunologic or inflammatory conditions, there may be an increased risk of migraine. In two population-based studies from the USA [8, 9], asthma and hay fever were more common in children with headache than in those without headache and asthma, as well as seasonal allergies were more common in adolescents with migraine than in those with ‘nonspecific headache’. Two clinic-based studies showed conflicting results. In one study there was no association between primary headaches and atopic disorders [10], whereas in another study, the risk of atopic disorders was significantly increased in migraine compared to tension-type headache (TTH) and in migraine with aura compared to migraine without aura and TTH [11].

The underlying aetiology of a possible comorbidity of migraine and atopic disorders might be due to an inflammatory disorder or due to the stress of two chronic conditions and therefore be a generic comorbid response. Regarding pharmacological treatment of migraine in patients with comorbid asthma or atopic disorders, the risk of sensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) must be considered, and beta-blockers should not be used for migraine prophylaxis to avoid exacerbation of asthma.

In adults there may be a relationship between cardiovascular disease and migraine. This has not been well described in children. As many of the cardiovascular syndromes in children are due to congenital heart defects, there may be a degree of compensation by the time the patients begin to express their migraine. The correlation between migraine and patent foramen ovale (PFO) is debatable. In a review published in 2008 [12], the authors identified 134 articles and included 18 which met a priori selection criteria. The estimated strength of association between PFO and migraine, reflected by summary odds ratios (ORs), was 5.13 [95 % confidence interval (CI) = 4.67–5.59], and between PFO and migraine with aura, the OR was 3.21 (95 % CI = 2.38–4.17). The grade of evidence was low. The association between migraine and PFO was OR 2.54 (95 % CI = 2.01–3.08). The grade of evidence was low to moderate. Six studies of PFO closure suggested improvement in migraine, but had a very low grade of evidence. In a review from 2016 [13] including the only two studies in children [14, 15], the authors suggest to close the debate on PFO and migraine and they emphasize the low quality of the studies. According to this review, in patients with PFO, the prevalence of migraine ranged between 16 and 64 %, and in patients with migraine, the prevalence of PFO ranged between 15 and 90 %. Observational studies that examined the effect of PFO closure on migraine showed a wide range of outcomes and all three randomized controlled trials failed to meet the primary endpoint. The authors conclude that ‘there is no good quality evidence to support a link between migraine and PFO and, that patients and providers should adhere to guidelines-recommended pharmacological, physical, and behavioural therapy for patients with migraine, even if a PFO is identified on echocardiography’.

With respect to other cardiac comorbidities, Jacobs et al. [6] identified in their review only one over other potential findings, i.e. QTc prolongation during a migraine attack in three of 13 children seen in an emergency department [16].

An increased risk for stroke in teenage girls and young women with probable migraine with aura has been noticed, particularly for those who smoke or use oral contraceptives, compared with women who do not have migraines.

In 2007, a study by MacClellan et al. assessed the link between probable migraine with visual aura (PMVA) and probable migraine without visual aura with ischemic stroke among groups of women [17]. Using data from a population-based, case-control study, they studied 386 women aged 15–49 years with first ischemic stroke and 614 age- and ethnicity-matched controls. Based on their responses to a questionnaire on headache symptoms, subjects were classified as having no migraine, probable migraine without visual aura or probable migraine with visual aura(PMVA) according to various factors including headache characteristics and various clinical features. The results showed that young women with PMVA had 1.5 greater odds of ischemic stroke (95 % CI = 1.1–2.0); the risk was highest in those with no history of hypertension, diabetes or myocardial infarction compared to women with no migraine. Women with PMVA who were current cigarette smokers and current users of oral contraceptives had 7.0-fold higher odds of stroke (95 % CI = 1.3–22.8) than did women with PMVA who were non-smokers and not users of oral contraceptives. Women with onset of PMVA within the previous year had 6.9-fold higher adjusted odds of stroke (95 % CI = 2.3–21.2) compared to women with no history of migraine. Their conclusion was that PMVA was associated with an increased risk of stroke, particularly among young women and teenage girls without other medical conditions associated with stroke. Behavioural risk factors, specifically smoking and oral contraceptive use, markedly increased the risk of PMVA, as did recent onset of PMVA. PMVA may be a risk factor for stroke or these patients may be genetically predisposed for both, with the migraine or the stroke being a comorbidity.

In 2015, Gelfand et al. published the first population-based study on the association between migraine and stroke in children and adolescents [18]. The authors included more than 1.5 million subjects aged 2–17 years. All of them were members of a health care delivery system that provides care to approximately 30 % of the population of northern California. Children and adolescents were classified as having migraine, if they had an ICD-9 code for migraine from any encounter, if migraine was mentioned in a significant health problem list or if pharmacy records showed a prescription of a migraine-specific medication. A stroke had occurred in eight of 88,164 migraineurs and in 80 of 1.3 million children and adolescents without headache. The ischemic stroke incidence rate was 0.9/100,000 person-years in migraineurs and 0.4/100,000 person-years in children and adolescents without headache. This difference was statistically not significant (incidence rate ratio (IR) 2.0, 95 % CI0.8–5.2). Similarly, the hemorrhagic stroke incidence rate (0.5/100,000 person-years in migraineurs and 0.9/100,000 person-years in subjects without headache) did not show a statistically significant difference between migraineurs and subjects without headache (IR 0.6, 95 % CI 0.2–2.0). In contrast, a post hoc analysis of adolescents aged 12–17 years showed an increased risk of ischemic stroke among those with migraine (IR 3.4, 95 % CI 1.2–9.5). Further studies are needed to confirm this finding.

In a population-based study, the prevalence of epilepsy was higher in children with headache than in headache-free children epilepsy (OR, 2.02; 95 % CI, 1.04–3.94) [8]. In a clinic-based study of paediatric epilepsy patients, it has been observed that a larger than expected proportion of these patients and their families have a history of migraine. This relationship appeared to be even higher for children who had migraine with aura [19]. Migraine and epilepsy are related with each other in various ways and share aspects of genetics, pathophysiology, semiology and treatment [20]. Winawer and Connors found a shared genetic susceptibility to migraine with aura in many types of nonacquired focal and generalized epilepsies [21]. Furthermore linkage studies in families with rolandic epilepsy and other types of epilepsy showed associations with genes related to familial hemiplegic migraine [19]. The precise mechanisms underlying the association of migraine and epilepsy remain unclear. Several studies have suggested an excessive neocortical hyperexcitability together with similar molecular and genetic substrates [20]. In epilepsy, neocortical hyperexcitability, abnormal hypersynchronous electrical discharges in neuronal cells and subsequent alterations of ion metabolism lead to recurrent seizures. In migraine, however, cortical spreading depression, rather than hypersynchronous discharges the basis for migraine aura and the trigger for headache [20].

Regarding the differential diagnosis of migraine aura and occipital epilepsy, it was suggested that elementary visual hallucinations cannot be anything else but visual seizures. They were found to be entirely different from migraine visual aura in colour, shape, size, location, movement, duration and development. In distinction, migraine visual aura with or without headache usually starts with predominantly flickering black and white, linear and zigzag patterns in the centre of the visual field, gradually expanding over minutes toward the periphery of the hemifield and often leaving a scotoma [20].

According to the beta version of the third edition of the International Classification of Headache Disorders (ICHD-3 beta) [22], headache related to epileptic seizures may be classified as migraine aura-triggered seizure (ICHD-3 beta 1.4.4), hemicrania epileptica (ICHD-3 beta 7.6.1) and post-ictal headache (ICHD-3 beta 7.6.2) with the latter being by far the most common [20].

Antiepileptic drugs (AEDs) which have been demonstrated to be safe and effective in the treatment of migraine include in particular divalproate and topiramate. The choice of AED in comorbid epilepsy and migraine should be guided by the underlying epilepsy syndrome and should consider a medication with prospective migraine preventive properties. The goals of treatment vary; for migraine the aim is reduction in frequency by at least 50 % and treatment is administered for 4–6 months, whereas for epilepsy the goal is seizure freedom for 2 years. Thus the epilepsy treatment dictates the duration of AED use.

Obesity is an area of growing concern in children and adolescents. Worldwide the incidence of obesity in childhood and adolescence is increasing. In obese children, there is an effect on both headache frequency and disability [6, 8, 23]. Pathophysiologically, serotonin, orexin, adiponectin and leptin have been suggested to have roles in both feeding and migraine [24]. The increased risk of headache and migraine related to obesity needs to be addressed in the overall treatment plan, as it appears that those children who can lower their BMI percentile have a greater improvement than those who don’t lose weight [24].

In a prospective study investigating the impact of a weight loss treatment on headache in 135 obese adolescent migraineurs participating in a 12-month programme including dietary education, physical training and behavioural treatment, the authors assessed decreases in weight, body mass index (BMI), waist circumference, headache frequency and intensity, use of acute medications and disability. Both lower baseline BMI and amount of weight loss were associated with better outcomes [25].

Disturbances in sleep can have both a biological and a behavioural basis. Sleep deprivation is one of the most common triggers of migraine in children and adolescents. This is complicated by the biological changes affecting sleep that occur during puberty, causing adolescents to have delayed sleep onset, which is hormonally controlled, in conflict with many school systems that require these children to wake earlier than is biologically natural.