Paediatric migraine

Guidelines for management of headache in childhood are available here

Introduction

• Primary headache
• Secondary headache

Epidemiology

• slight predominance in boys in the pre-pubertal years, and changing to a girl predominance in young adulthood.
• Epidemiological studies
  • Isik et al 2009[1]
    • study of 2669 children in Istanbul, Turkey
    • 46·2% of children aged 5–13 years reported having a debilitating headache
    • 3·4% of these children having migraine and a further 8·7% having probable migraine.
    • Independent factors that contributed to the manifestation of migraine in these children included
      • older age
      • female sex
      • a family history of migraine
      • smoking in the household
      • an inverse relationship with social economic status.
  • Santinello et al 2009[2] Italy
    • Italian study of 4386 adolescents aged 11, 13, and 15 years
    • 40% reported having at least one headache a week.
    • high frequency of headaches correlated with a perception of teacher unfairness towards the student and a poor recognition of the headaches as a problem.
  • Split and Neuman 1999 [3]
    • 351 individuals aged 15–19 years
    • 28% had migraine
    • 19% having migraine without aura
    • 9% having migraine with aura
  • Stewart et al 1991[4]
    • 10 169 individuals aged 12–29 years
    • onset of migraine with or without aura was significantly earlier in male participants than in female participants
    • aura occurring in nearly a quarter of individuals.

Pathophysiology

• Migraine involves a cascade of events that lead to recurrent inappropriate activations of the trigeminocervical pain system.
• Initiation
• Activation
• possible role for dopaminergic mechanisms in migraine[5]
  • Dopamine is currently considered to contribute to the pathophysiology of migraine, and dopamine receptor antagonists are prescribed in the treatment of acute migraine.

Genetics of migraine

• Several population-based and twin-based genetic studies,[6, 7, 8, 9, 10, 11, 12] have looked at the genetic influence, the shared environmental influence, and the non-shared environmental influences.
• The best-fitting model[7, 13] showed a genetic influence of 60–70%, with the remaining risk derived from a non-shared environmental influence.
• Thus migraine is a genetic disease with environmental factors contributing to its expression.

see /Genetics of migraine for a detailed discussion.

Biological changes in migraine

• Immunological and inflammatory changes have been linked to migraine in children.
• Bockowski et al 2009[14] reported that children with a history of migraine had detectable levels of interleukin 1α that were not seen in children with a history of tension-type headache, and the concentrations of both soluble tumour necrosis factor receptor 1 and tumour necrosis factor were increased in children with migraine.
• There are currently no biological markers for migraine
  • potential biomarkers include
    • increased levels of calcitonin gene-related peptide [15]
    • decreased levels of coenzyme Q10[16]

Hormones and migraine

• Hormonal changes might aaffect the pathophysiology of paediatric migraine in a similar way to adults and could partly explain the shift in predominance to girls during adolescence.
• Menstrual migraine seems to be due to hormonal sensitivity.[17, 18, 19, 20]

Neurophysiology of migraine

Neurophysioligical changes in migraine

• Adult patients with migraine have
  • interictal trigeminal sensitisation as shown by an altered blink reflex[21, 22, 23, 24, 25]
  • altered visual-evoked responses during the oddball paradigm[26]
  • altered auditory responses[27, 28, 29]
• Unay et al 2008[30] evaluated visual evoked potentials (VEP) and brainstem auditory evoked potentials (BAEP) in 37 children (mean age 10.4yrs) with headache and found that P100 latency and amplitudes of migraine patients were significantly higher than children with tension-type headache and control subjects.
• Oelkers-Ax et al 2005[31] investigated response and habituation to pattern-reversal VEPs and its maturation in 102 children with primary headache (migraine with and without aura, tension-type headache) and 79 healthy controls from 6 to 18 years. found diminished N180 latency reduction with age in migraineurs providing further evidence that maturation of visual information processing is altered in migraine.By contrast, the brainstem auditory-evoked potential did not vary between any of the group
• Vollono et al 2010 [32] compared the recovery cycle of somatosensory evoked potentials (SEPs) in 11 children with migraine without aura before and after treatment with topiramate found that in nine patients, who had a significant reduction in headache frequency after treatment, the recovery cycles of the P24 (P = 0.03) and N30 (P < 0.005) potentials were longer after than before topiramate treatment while in two migraineurs who did not show any improvement, the recovery cycles of the cortical SEP components were even shorter after treatment suggesting that topiramate efficacy in paediatric migraine prophylaxis is probably related to restored cortical excitability.
• Siniatchkin et al 2009[33] using trancranial magnetic stimulation to examine cortical excitability in children showed altered occipital response (but not motor cortex response) at the time of the migraine .The threshold for phosphene generation was lower for patients with migraine than for healthy controls for all times tested, whereas the threshold was increased before an attack in patients. This finding suggests a neurophysiological sensitivity in adolescent migraine that can change during the migraine cycle, which has implications for treatment.
• Valeriani et al 2009[34] found that habituation to mismatch negativity and the P300 responses were substantially slower in children with migraine or TTH than in controls, and the P300 habituation deficit was associated with behavioural difficulties.[34] This observation shows that ongoing neurophysiological changes in paediatric patients with migraine could affect their behavioural presentation.

Allodynia

Cutaneous allodynia due to central sensitisation has been studied in adults as a clinical marker that reflects migraine-related neurophysiological changes.[57], [58], [59], [60], [61] and [62] Individuals who have this symptom during migraine might have altered responses to treatment[63], [64] and [65] and possible disease progression. In children, allodynia is beginning to be examined and only small studies have been done so far. [35]

Diagnosis and evaluation

The International Headache Society has established diagnostic criteria—the ICHD-II—for all headache subtypes including primary and secondary headaches.[36] These criteria have been widely used for the clinical characterisation of headaches and as a basis for research in headaches. A key feature of these criteria is the separation of headaches thought to be intrinsic to the nervous system (primary headaches) and headaches directly attributable to another cause (secondary headaches).

Diagnostic criteria

Evaluation and managment of paediatric migraine

In the initial evaluation of a patient with headache, the first step is to identify any secondary causes. In general, once a suspected secondary cause is effectively treated, the headaches should resolve. If this is not the case, additional investigation and a different diagnosis is necessary.

ICHD-II=second edition of the International Classification of Headache Disorders. NSAID=non-steroidal anti-inflammatory drug. PedMIDAS=paediatric migraine disability assessment.

Once secondary aetiologies have been eliminated, a diagnosis of a primary headache can be made. The ICHD-II has three main categories of primary headaches—migraine, TTH, and trigeminal autonomic cephalalgias (including cluster headaches)—and a fourth category for rare primary headaches that do not fall into one of the main classifications.

Migraine can be subdivided into migraine without aura, migraine with aura, childhood periodic syndromes, retinal migraine, migraine complications, and probable migraine. In young children, the diagnosis of the childhood periodic syndromes (thought to be precursors of migraine) are often first recognised because a child might not focus on head pain, but instead on some of the abdominal symptoms (cyclic vomiting and abdominal migraine) or vertigo (benign paroxysmal vertigo of childhood). As the child grows older they are better able to describe the head pain and the presence of migraine becomes more evident.

Additional aspects of migraine in children, particularly during their adolescent years, include chronic migraine and status migrainosus. However, in many children, not all the symptoms required by ICHD-II are present and a diagnosis of probable migraine must be made. The specific ICHD-II criteria for migraine without aura and migraine with aura are listed in the panel.

ICHD-II criteria for the diagnosis of migraine[36]

• Migraine without aura (ICHD-II, 1.1)
  • Previously used terms :Common migraine, hemicrania simplex
  • Description: Recurrent headache disorder manifesting in attacks lasting 4–72 h. Typical characteristics of the headache are unilateral location, pulsation quality, moderate or severe intensity, aggravation by routine physical activity, and association with nausea and/or photophobia and phonophobia
  • Diagnostic criteria

A.At least five attacks* fulfilling criteria B–D

B.Headache attacks lasting 4–72 h (untreated or unsuccessfully treated)† ‡ §

C.Headache has at least two of the following characteristics:

1. Unilateral location ¶ ||
2. Pulsating quality**
3. Moderate or severe pain intensity
4. Aggravation by or causing avoidance of routine physical activity (eg, walking or climbing stairs)

D.During headache at least one of the following:

1. Nausea and/or vomiting
2. Photophobia and phonophobia††

E.Not attributed to another disorder‡‡

• Migraine with aura (ICHD-II, 1.2)
  • Previously used terms :Classic or classical migraine, ophthalmic, hemiparaesthetic, hemiplegic, or aphasic migraine, migraine accompagnée, complicated migraine
  • Description: disorder manifesting in attacks of reversible focal neurological symptoms that usually develop gradually over 5–20 min and last for <60 min. Headache with the features of migraine without aura (1.1) usually follows the aura symptoms. Less commonly, headache lacks migrainous features or is completely absent
  • Diagnostic criteria

A.At least two attacks fulfilling criterion B

B.Migraine aura fulfilling criteria B and C for one of the subforms 1.2.1–1.2.6

C.Not attributed to another disorder

• Typical aura with migraine headache (ICHD-II, 1.2.1)
  • Description: Typical aura consisting of visual and/or sensory and/or speech symptoms. Gradual development, duration ≤1 h, a mix of positive and negative features, and complete reversibility characterise the aura, which is associated with a headache fulfilling criteria for 1.1 Migraine without aura
  • Diagnostic criteria

A.At least two attacks fulfilling criteria B–D

B.Aura consisting of at least one of the following, but no motor weakness:

1. Fully reversible visual symptoms including positive features (eg, flickering lights, spots or lines) and/or negative features (ie, loss of vision)
2. Fully reversible sensory symptoms including positive features (ie, pins and needles) and/or negative features (ie, numbness)
3. Fully reversible dysphasic speech disturbance

C.At least two of the following:

1. Homonymous visual symptoms§§ and/or unilateral sensory symptoms
2. At least one aura symptom develops gradually over ≥5 min and/or different aura symptoms occur in succession over ≥5 min
3. Each symptom lasts ≥5 min and ≤60 min

D.Headache fulfilling criteria B–D for 1.1 Migraine without aura begins during the aura or follows within 60 min

E.Not attributed to another disorder

ICHD-II = second edition of the International classification of headache disorders. *= Differentiating between 1.1 Migraine without aura and 2.1 Infrequent episodic tension-type headache can be difficult. Therefore atleast 5 attacks are required. Individuals who otherwise meet criteria for 1.1 Migriane without aura but have had fewer attacks should be categorised as 1.6.1 probable migrine without aura.

†= When the patient falls asleep during migraine and wakes up without it, duration of the attack is reckoned until the time of awakening.

‡= In children, attacks can last 1–72 h (although the evidence for untreated durations of <2 h in children requires corroboration by prospective diary studies).

§= When attacks occur for ≥15 days per month for >3 months, categorise as 1.1 Migraine without aura and as 1.5.1 Chronic migraine.

¶= Migraine headache is commonly bilateral in young children; an adult pattern of unilateral pain usually emerges in late adolescent or early adult life

||= Migraine headache is usually frontotemporal. Occipital headache in children, whether unilateral or bilateral, is rare and calls for diagnostic caution; many cases are attributable to structural lesions

**= Pulsating means throbbing or varying with the heartbeat.

†† In young children, photophobia and phonophobia can be inferred from their behaviour.

‡‡ History and physical and neurological examinations do not suggest any of the disorders listed in ICHD-II groups 5–12, or history and/or physical and/or neurological examinations do not suggest such disorder but this is ruled out by appropriate investigations, or such a disorder is present but attacks do not occur for the first time in close temporal relation to the disorder.

§§ Additional loss of blurring of central vision can occur.

---

In response to criticisms about the incompleteness of the original criteria, the ICHD-II criteria include footnotes for migraine without aura, resulting in an improvement in the specificity and sensitivity, although gaps still remain.[37, 38, 39, 40]. The points raised in the footnotes are intended to acknowledge that childhood migraine tends to be shorter in duration (down to 1 h with diary confirmation), that sleep should be included as part of the duration, that the location is more likely to be bilateral (typically frontal-temporal), and that photophobia and phonophobia could be inferred by the parents or care providers on the basis of the child's actions. One additional footnote says that if the location is exclusively occipital, further assessment is warranted.

The ICHD-II criteria were tested in tertiary clinics and found to be an improvement on the previous criteria. Additional improvements were gained when the requirements for a lower time duration and focal location (in contrast to diffuse headache pain) were removed and there was modification of the required associated symptoms.[37] These suggestions increased the number of children who met the criteria, but there remained a subgroup of patients with migraine who did not meet the criteria. Further work is necessary to develop improved markers for the identification of paediatric migraine.

Even with these limitations, the evaluation and diagnosis of paediatric headaches should involve the use of these criteria as a guideline. Standardised questionnaires with a semi-structured interview can be used to obtain a more thorough evaluation.[41] Such an approach has been shown to be very sensitive and specific in making the appropriate diagnosis of headache.[42] This evaluation must incorporate the children's responses and should not just be completed by the parents. Parents might not always be completely aware of the child's symptoms or the effect of the headaches. In an epidemiological study of 3461 parents and children aged between 7 and 14 years, there was a high correlation in the reports of frequency between the children and their parents, but the correlation for other features was much lower, with the parents' perception of depression and anxiety being the least reliable.[43]

Examination

In addition to a complete history, general examination, and neurological examination, a comprehensive headache examination should be done.[44] This is an extension of the neurological examination to include assessments for neck tenderness and stability, the stability of the temporomandibular joint, sinus and facial tenderness including peripheral nerve tenderness, and general cranial palpation. One useful test to assess for sinus-related symptoms is the Muller's sign, when patients pressurise their sinus and then cough to create a brief vacuum, thus enabling the evaluation of the openness of the sinuses. This test can be used to rule out sinus headache as the cause of the headache.

Drawings

In young children, obtaining a complete history can be difficult. To assist with this, the use of children's drawings can be both sensitive and specific in the diagnosis of paediatric headaches.[45, 46]. In a study of 124 children with headache (32·2% migraine, 37·9% TTH, and 29·8% other headaches), identification of elements of the children's drawings enabled differentiation of the three diagnoses. The drawings also served as a basis for standardised drawings for future paediatric patients to examine to facilitate their diagnosis.[47]

Neuroimaging

Guidelines for the evaluation of children with headaches have been developed through collaboration between the American Academy of Neurology, the Child Neurology Society, and the American Headache Society.[48] The authors of these guidelines reviewed the available evidence for the evaluation of children with headaches and found that the neurological examination is the most crucial test for identifying potential serious complications, while also confirming that occipital location warranted further evaluation. In most cases of primary headaches that are long standing, recurrent, and do not change with a normal neurological examination, imaging studies are not necessary. When further evaluation is needed, an MRI examination is the most sensitivite test to identify structural abnormalities and should be the preferred neuroimaging test.[49] A routine MRI is usually sufficient, unless there are clinical and physical findings that would suggest the need to undertake further imaging studies, such as magnetic resonance angiography when a vascular disorder is suspected or diffusion-weighted imaging when there is an acute change or injury. Disability and effect on quality of life

As part of the clinical history, the effect of the headache on the child's quality of life and the specific disabilities caused need to be assessed. A recent review of the effect of paediatric migraine reported 33 studies that investigated this question and the tools used, and showed that, although the quality was inconsistent, there was a substantial effect of migraine on the lives of the patients and their families.[50]

Disability and Quality of life

Quality of life

One of the most widely used tools for the assessment of quality of life for children and adolescents is the paediatric quality of life inventory (PedsQL 4.0).81 This tool is easy to implement and addresses the quality of life in a disease-independent manner. Similar to adults, the quality of life for children with headaches can be measured in a developmentally appropriate manner, and headache seems to have an effect on quality of life that is similar to that of other chronic disease.[82], [83] and [84] On the basis of clinical experience, this effect seems to improve with treatment, although there might be a persistent effect even after successful treatment.

Disability

Tools have been developed to assess migraine-specific disability in adults: ie, the migraine disability assessment (MIDAS) and headache impact test (HIT-6). Headache and migraine are unique in their episodic nature and their effects can therefore be more variable than those of other chronic health disorders. To minimise this day-to-day and week-to-week variation, MIDAS was originally developed to be used over a 3-month period. For children and adolescents, PedMIDAS has been developed.[51, 52] This tool can be easily implemented in clinical practice and can be used to assess the disability of an individual patient, the need for preventive medication, and the response to treatment. A recent study of 3963 children aged 13–15 years in Taiwan showed the wide-scale population applicability of PedMIDAS.11 In this study, TTH was the most common headache type in 27·6% of participants, whereas migraine with or without aura occurred in 12·2%, and probable migraine occurred in 11·2% of particpants. Patients with migraine had a higher PedMIDAS score than patients with TTH; if this score was greater than 31 (moderate to severe disability), patients had a higher risk of depression, and increased severity and frequency of headaches.

The disability and effects on quality of life of migraine in children and adolescents are increasingly being recognised. Assessment of these effects can help guide the referral to specialty centres and measurement of the long-term outcome of migraine.

Comorbid conditions

Additional diseases and conditions can complicate migraine diagnosis, management, and outcome. The understanding of the role of comorbid conditions in paediatric migraine is limited, with interactions between migraine and other conditions yet to be clearly delineated. Recognition of these additional disorders could alter treatment choices, such as use of antiepileptic drugs in patients with seizures or antidepressant drugs when patients have depression, anxiety, or emotional disorders, or might necessitate adjustment of treatment on the basis of side-effects, such as appetite reduction, or lifestyle factors, such as diet and exercise, when there is obesity. The common occurrence of secondary conditions that might directly contribute to headaches in children can confuse recognition of the underlying aetiology and delay the diagnosis of primary headaches, and these comorbid conditions might also affect the underlying pathophysiological basis of the migraine in children.

Several conditions have a comorbid relationship with migraine, such as asthma and allergic disorders,[53] and [54] obesity,[55] and [56] epilepsy,[57], [58], [59] and [60] sleep disorders,[61], [62], [63], [64], [65] and [66] and psychological or emotional disorders.[67], [68] and [69] The mechanisms by which these comorbid conditions alter the underlying pathophysiology and thus affect the manifestation of migraine are largely unknown. At the biological level, the comorbid disorders might have a common neuropathological pathway, whereas from a behavioural perspective, the difficulty in coping with multiple illnesses might alter the manifestation of the headache.

Allergies and sinus disease

In adults, one of the most frequently misdiagnosed headaches is sinus headache.[70, 71] Allergy and asthma symptoms could lead to the same confusion in children and adolescents. In our database of about 5000 children who presented to a tertiary headache centre, asthma was reported in 12·0% of the children. By contrast, screening of records from a tertiary asthma and allergy clinic showed that almost 45·9% of patients had recurrent headaches.106 Comparison between patients presenting to an allergy clinic and patients seen in our headache centre showed that patients with allergies were more likely to have a lower frequency and severity of headaches.

Head injury

Head injury is another frequent event in children and adolescents. Many children can recall a substantial or memorable head injury. When such an injury occurs in a patient with a history of recurrent headache or migraine, it can often exacerbate the underlying primary headache disorder and complicate the evaluation and management, possibly affecting their overall outcome.[72, 73, 74, 75]

Obesity

As the incidence of obesity is increasing worldwide, there is growing recognition of its co-occurrence with headache disorders and its negative effects on migraine in adults. The association between obesity and migraine is also present in children and adolescents. In a multicentre study of children with migraine, those with a body–mass index percentile at the extremes (<5th percentile and >95th percentile) and those at risk of obesity (85th to 95th percentile) were more likely to have an increased frequency of headaches and disability. Intervention in children who were obese or overweight through healthy weight control led to a greater improvement in frequency of headaches than was seen in children whose body–mass index remained high or increased.[55]

Sleep

Sleep disturbances affect the expression of migraine, with sleep deprivation or altered sleep patterns triggering migraines, and might also have a comorbid association with migraine. In a study of 1073 adolescents, the most frequent triggering factor for both migraine and non-migraine headaches was “bad sleep.”111 In a separate study, these sleep disturbances were identified as insufficient sleep (65·7%), daytime sleepiness (23·3%), difficulty falling asleep (40·6), and night waking (38%).[62]

Psychological factors

Psychological factors can have a complicated role in paediatric migraine and have been addressed in small studies, with contradictory findings.112 In a case-controlled study of 47 children with migraine (aged 8–14 years), mothers perceived emotional and behavioural difficulties in these children,102 whereas in a separate study, the classmates of these same children identified them to have higher levels of leadership and popularity than their peers.113 Psychological factors and feelings about school can have a substantial effect on a child's headaches, with school phobia and anxiety contributing to headache frequency; furthermore, there is an increased risk of problems in school and family life, as well as psychiatric disorders, in children with migraine.[76]

These problems might escalate, resulting in a substantial effect on the child's life, potentially leading to suicidal ideation. A study of 3963 adolescents in Taiwan showed that 8·5% had suicidal ideation, with an increased odds ratio of 2·9 for adolescents with migraine, which increased to 4·6 for patients who had migraine with aura.115 This finding was affected by both headache frequency and disability as measured with PedMIDAS.

Treatment

The treatment of paediatric migraine can be divided into pharmacological (both acute and preventive strategies) and biobehavioural interventions to minimise the effects of the attacks (figure). The goals of treatment need to be determined at the initial visit, and should include a rapid return to normal function with acute treatment, and a reduction in the frequency and effect of the migraine with preventive and biobehavioural treatment. These strategies are often not used in general practice. In a study of 151 children, only 30·2% were prescribed an appropriate dose of ibuprofen, with only 26·5% being instructed to treat the headache early, while lifestyle adjustments were recommended in less than 15% and only 8% were asked to keep a headache diary.116 Thus, a crucial component of management of paediatric headache is education of the patients and parents on the incorporation of all these strategies.

Acute treatment

The goal of acute treatment of paediatric migraine should be a consistent response with minimum side-effects and a rapid return to normal function. At present, only almotriptan has been approved by the US Food and Drugs Administration (FDA), while nasal sumatriptan and zolmitriptan have been approved in Europe by the European Medicines Agency (EMEA) for acute treatment of adolescent migraine. Detailed analysis and guidelines have been developed.[77] There have been few grade I studies, but the effective acute drugs fell into two broad groups: non-steroidal anti-inflammatory drugs (NSAIDs) and triptans (table 1). Subsequently, additional studies have indicated that NSAIDs (particularly ibuprofen) are effective when used early in the attacks at an adequate dose (7·5–10·0 mg/kg per dose) and that triptans are effective when NSAIDs do not completely relieve symptoms, particularly during the more severe attacks.

Placebo effect

One of the reasons for there being few studies with positive results is study design, which has led to a high placebo response rate, ranging from 38% to 53% for pain relief and 17% to 26% for pain freedom at 2 h.[78] An analysis of eight crossover studies and 11 parallel group studies of acute treatment showed that crossover studies had a lower placebo response rate (19·2% vs 27·1% for pain-free response), whereas in an analysis of ten preventive treatment studies, only a trend for decreased placebo response rate in crossover trials was reported.[79] This analysis indicated that the overall response to the active drug in paediatric and adolescent studies was similar to that in adult studies. This placebo response effect seems to be dependent on age, as it decreases significantly when examined in 10-year increments of age.[80]

Triptans

In a double-blind, placebo-controlled three-way crossover study of 96 children aged 6–17 years, rizatriptan (5 mg dose for children who were 20–39 kg and 10 mg dose for children who were >40 kg) was consistently more effective than placebo at 2 h. Headache relief was achieved in 74% of patients after the first treatment dose and in 73% after the second treatment dose, while 36% of patients had headache relief after placebo.[81] Furthermore, rizatriptan was more effective at 1 h (50% and 55%) compared with placebo (29%).

The efficacy of zolmitriptan nasal spray was studied in 248 adolescents in a multicentre, randomised, double-blind, placebo-controlled, two-way, two-attack, crossover study that involved a unique single-blind, placebo-challenge design.134 Of 171 patients who treated at least one attack, zolmitriptan nasal spray (5 mg) was more effective than placebo at 1 h, with a 58·1% response for zolmitriptan compared with 43·3% for placebo. This study took into account many of the placebo response concerns that had complicated previous studies, while also using a cross-over design.

A randomised, double-blind, placebo-controlled trial of almotriptan in 866 adolescents (12–17 years of age) showed a 2-h pain-relief rate that was significantly higher for all doses of almotriptan (6·25 mg, 71·8%; 12·5 mg, 72·9%; and 25 mg, 66·7%) compared with placebo (55·3%).[82] Further analysis indicated a superior sustained response (ie, 24 h without headache recurrence) with improvement in migraine-associated symptoms for almotriptan compared with placebo, particularly with the 12·5 mg dose.

In adults, the multimechanistic approach combining NSAIDs with triptans is an effective way to improve the acute treatment of migraine.[83] and [84] However, this approach has not yet been investigated for paediatric or adolescent patients.

Infusion treatment

When acute treatment does not relieve the headache, patients frequently visit the emergency department[85] or infusion centres. Studies of emergency department treatment are often complicated by a mixture of headache types, and this variability needs to be considered when assessing the effectiveness of these treatments.[74] and [86] Owing to this wide variety of headache presentations, the treatment is often not well directed.

In a study of 382 children in four regional emergency departments in Canada, most received either no treatment (44·2%) or simple oral analgesics (23·3%), with dopamine antagonists prescribed in 20·7%, opiates in 5·5%, ketolorac in 4·7%, and dihydroergotamine in 1·0%.142 The paediatric emergency departments were more likely to treat these children with dopamine antagonists, whereas adult emergency departments were more likely to treat them with opiates; more children with migraine received treatment, particularly dopamine antagonists, than did children presenting with other headache types.

When these emergency department treatments are not successful, inpatient treatment might be necessary. In adults, this treatment has typically included the use of dihydroergotamine. In a chart review of 32 consecutive patients admitted for status migrainosus treatment, 24 became headache-free, with a clear improvement in nearly all the patients.[87] Nausea was the most common side-effect but otherwise dihydroergotamine was well tolerated.

Medication overuse

One aspect of acute treatment that needs to be included in any treatment plan is the avoidance of medication overuse. This is a common component of chronic daily headache that can be avoided by limiting the number of headaches treated with acute medications. Clinical experience suggests that non-specific analgesics should be used fewer than 2–3 times per week, and migraine-specific drugs should be used fewer than 6 times per month.

On the basis of controlled studies of acute treatment to date, the general conclusions that can be drawn are that NSAIDs (particularly ibuprofen) are effective at appropriate doses (7·5–10 mg/kg) when taken early and when these drugs are used fewer than 2–3 times per week to minimise the risk of medication overuse. When this approach is not consistently effective, triptans can be a well-tolerated and successful addition to the acute treatment. However, data from controlled studies of triptans are limited by the high placebo response rate and design problems that have not completely accounted for the developmental differences in children of various ages, including the differences from adults. When treatment with NSAIDs or triptans at home is ineffective, the use of dopamine antagonists with intravenous NSAIDs in the emergency department and infusion centres seems to be effective,.[88] but larger studies are needed to confirm this result. Intravenous dihydroergotamine remains one of the few options with supporting evidence for inpatient management of migraine in children..[87]

Preventive treatment

When the headaches are frequent (more than once a week) or disabling (PedMIDAS score >30 [grade III or IV]), preventive treatment should be considered. The goal of preventive treatment is to reduce the headache frequency (to <1–2 per month), with a decreased disability (PedMIDAS <10) for a sustained period of time (4–6 months). This goal should have full involvement of the patients and parents to ensure full adherence and minimisation of side-effects. Additionally, the presence of comorbid conditions can guide the choice of treatment. No drugs are approved in the USA for the prevention of paediatric migraine. The American Academy of Neurology practice guidelines for headache identified flunarazine as having sufficient evidence for efficacy but this drug is not available in the USA, whereas flunarizine has been approved for use in Europe.[77]. See here for guidelines/practice parameters on childhood headache

References

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4. WF Stewart, MS Linet, DD Celentano, M Van Natta and D Ziegler, Age- and sex-specific incidence rates of migraine with and without visual aura, Am J Epidemiol 134 (1991), pp. 1111–1120.abstract

7. M Gervil, V Ulrich, KO Kyvik, J Olesen and MB Russell, Migraine without aura: a population-based twin study, Ann Neurol 46 (1999), pp. 606–611.abstract

10. V Ulrich, M Gervil, KO Kyvik, J Olesen and MB Russell, Evidence of a genetic factor in migraine with aura: a population-based Danish twin study, Ann Neurol 45 (1999), pp. 242–246.abstract

14. L Bockowski, W Sobaniec and B Zelazowska-Rutkowska, Proinflammatory plasma cytokines in children with migraine, Pediatr Neurol 41 (2009), pp. 17–21.

15. PC Fan, PH Kuo, SH Chang, WT Lee, RM Wu and LC Chiou, Plasma calcitonin gene-related peptide in diagnosing and predicting paediatric migraine, Cephalalgia 29 (2009), pp. 883–890.

16. AD Hershey, SW Powers and AL Vockell et al., Coenzyme Q10 deficiency and response to supplementation in pediatric and adolescent migraine, Headache 47 (2007), pp. 73–80.

17. VT Martin and M Behbehani, Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis—part 2, Headache 46 (2006), pp. 365–386.

18. VT Martin and M Behbehani, Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis—part I, Headache 46 (2006), pp. 3–23.

19. MJ Crawford, L Lehman and S Slater et al., Menstrual migraine in adolescents, Headache 49 (2009), pp. 341–347.

20. B Kroner-Herwig and N Vath, Menarche in girls and headache—a longitudinal analysis, Headache 49 (2009), pp. 860–867.

21. Z Katsarava, G Lehnerdt, B Duda, J Ellrich, HC Diener and H Kaube, Sensitization of trigeminal nociception specific for migraine but not pain of sinusitis, Neurology 59 (2002), pp. 1450–1453.

22. H Kaube, Z Katsarava, S Przywara, J Drepper, J Ellrich and HC Diener, Acute migraine headache: possible sensitization of neurons in the spinal trigeminal nucleus?, Neurology 58 (2002), pp. 1234–1238.

23. M De Marinis, A Pujia, L Natale, E D'Arcangelo and N Accornero, Decreased habituation of the R2 component of the blink reflex in migraine patients, Clin Neurophysiol 114 (2003), pp. 889–893.

24. Z Katsarava, N Giffin, HC Diener and H Kaube, Abnormal habituation of ‘nociceptive’ blink reflex in migraine—evidence for increased excitability of trigeminal nociception, Cephalalgia 23 (2003), pp. 814–819.

25. R Burstein, D Levy and M Jakubowski, Effects of sensitization of trigeminovascular neurons to triptan therapy during migraine, Rev Neurol 161 (2005), pp. 658–660.

26. S Evers, B Bauer, KH Grotemeyer, G Kurlemann and IW Husstedt, Event-related potentials (P300) in primary headache in childhood and adolescence, J Child Neurol 13 (1998), pp. 322–326.

27. W Wang and J Schoenen, Interictal potentiation of passive “oddball” auditory event-related potentials in migraine, Cephalalgia 18 (1998), pp. 261–265.

28. M Siniatchkin, P Kropp and WD Gerber, What kind of habituation is impaired in migraine patients?, Cephalalgia 23 (2003), pp. 511–518.

29. G Buodo, D Palomba, M Sarlo, C Naccarella and PA Battistella, Auditory event-related potentials and reaction times in migraine children, Cephalalgia 24 (2004), pp. 554–563.

30. B Unay, UH Ulas, B Karaoglu, E Eroglu, R Akin and E Gokcay, Visual and brainstem auditory evoked potentials in children with headache, Pediatr Int 50 (2008), pp. 620–623.

31. R Oelkers-Ax, P Parzer, F Resch and M Weisbrod, Maturation of early visual processing investigated by a pattern-reversal habituation paradigm is altered in migraine, Cephalalgia 25 (2005), pp. 280–289.

32. C Vollono, D Ferraro, R Miliucci, F Vigevano and M Valeriani, The abnormal recovery cycle of somatosensory evoked potential components in children with migraine can be reversed by topiramate, Cephalalgia (2009) 10.1111/j.1468-2982.2009.01892.x published online June 1..

33. M Siniatchkin, AL Reich, AJ Shepherd, A van Baalen, HR Siebner and U Stephani, Peri-ictal changes of cortical excitability in children suffering from migraine without aura, Pain 147 (2009), pp. 132–140.

34. M Valeriani, F Galli and S Tarantino et al., Correlation between abnormal brain excitability and emotional symptomatology in paediatric migraine, Cephalalgia 29 (2009), pp. 204–213.

35. T Eidlitz-Markus, A Shuper, O Gorali and A Zeharia, Migraine and cephalic cutaneous allodynia in pediatric patients, Headache 47 (2007), pp. 1219–1223.

37. AD Hershey, P Winner and MA Kabbouche et al., Use of the ICHD-II criteria in the diagnosis of pediatric migraine, Headache 45 (2005), pp. 1288–1297.

38. MM Lima, NA Padula, LC Santos, LD Oliveira, S Agapejev and C Padovani, Critical analysis of the international classification of headache disorders diagnostic criteria (ICHD I-1988) and (ICHD II-2004), for migraine in children and adolescents, Cephalalgia 25 (2005), pp. 1042–1047.

39. LN Rossi, S Vajani, I Cortinovis, F Spreafico and L Menegazzo, Analysis of the International Classification of Headache Disorders for diagnosis of migraine and tension-type headache in children, Dev Med Child Neurol 50 (2008), pp. 305–310.

40. S Ruangsuwan and S Sriudomkajorn, 375 childhood primary headache: clinical features, the agreement between clinical diagnosis and diagnoses using the international classification of headache disorders in Thai children, J Med Assoc Thai 90 (2007), pp. 1309–1316.

41. AD Hershey, SW Powers, AL Bentti and TJ Degrauw, Effectiveness of amitriptyline in the prophylactic management of childhood headaches, Headache 40 (2000), pp. 539–549.

42. L Valentinis, F Valent, M Mucchiut, F Barbone, P Bergonzi and G Zanchin, Migraine in adolescents: validation of a screening questionnaire, Headache 49 (2009), pp. 202–211.

43. B Kroner-Herwig, L Morris, M Heinrich, J Gassmann and N Vath, Agreement of parents and children on characteristics of pediatric headache, other pains, somatic symptoms, and depressive symptoms in an epidemiologic study, Clin J Pain 25 (2009), pp. 58–64.

44. SL Linder, Understanding the comprehensive pediatric headache examination, Pediatr Ann 34 (2005), pp. 442–446.

45. CE Stafstrom, SR Goldenholz and DA Dulli, Serial headache drawings by children with migraine: correlation with clinical headache status, J Child Neurol 20 (2005), pp. 809–813.

46. CE Stafstrom, K Rostasy and A Minster, The usefulness of children's drawings in the diagnosis of headache, Pediatrics 109 (2002), pp. 460–472.

47. K Wojaczynska-Stanek, R Koprowski, Z Wrobel and M Gola, Headache in children's drawings, J Child Neurol 23 (2008), pp. 184–191.

48. DW Lewis, S Ashwal and G Dahl et al., Practice parameter: evaluation of children and adolescents with recurrent headaches: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society, Neurology 59 (2002), pp. 490–498.

49. DW Lewis and D Dorbad, The utility of neuroimaging in the evaluation of children with migraine or chronic daily headache who have normal neurological examinations, Headache 40 (2000), pp. 629–632.

50. D Kernick and J Campbell, Measuring the impact of headache in children: a critical review of the literature, Cephalalgia 29 (2009), pp. 3–16.

51. AD Hershey, SW Powers, AL Vockell, S LeCates, MA Kabbouche and MK Maynard, PedMIDAS: development of a questionnaire to assess disability of migraines in children, Neurology 57 (2001), pp. 2034–2039.

52. AD Hershey, SW Powers, AL Vockell, SL LeCates, A Segers and MA Kabbouche, Development of a patient-based grading scale for PedMIDAS, Cephalalgia 24 (2004), pp. 844–849.

53. M Ku, B Silverman, N Prifti, W Ying, Y Persaud and A Schneider, Prevalence of migraine headaches in patients with allergic rhinitis, Ann Allergy Asthma Immunol 97 (2006), pp. 226–230.

54. F Gurkan, A Ece, K Haspolat and B Dikici, Parental history of migraine and bronchial asthma in children, Allergol Immunopathol 28 (2000), pp. 15–17.

55. AD Hershey, SW Powers and TD Nelson et al., Obesity in the pediatric headache population: a multicenter study, Headache 49 (2009), pp. 170–177.

56. O Pinhas-Hamiel, K Frumin and L Gabis et al., Headaches in overweight children and adolescents referred to a tertiary-care center in Israel, Obesity (Silver Spring) 16 (2008), pp. 659–663.

57. SB Stevenson, Epilepsy and migraine headache: is there a connection?, J Pediatr Health Care 20 (2006), pp. 167–171.

58. P Piccinelli, R Borgatti and F Nicoli et al., Relationship between migraine and epilepsy in pediatric age, Headache 46 (2006), pp. 413–421.

59. LE Yamane, MA Montenegro and MM Guerreiro, Comorbidity headache and epilepsy in childhood, Neuropediatrics 35 (2004), pp. 99–102.

60. JM Pellock, Understanding co-morbidities affecting children with epilepsy, Neurology 62 (2004), pp. S17–S23.

61. VA Miller, TM Palermo, SW Powers, MS Scher and AD Hershey, Migraine headaches and sleep disturbances in children, Headache 43 (2003), pp. 362–368.

62. DK Gilman, TM Palermo, MA Kabbouche, AD Hershey and SW Powers, Primary headache and sleep disturbances in adolescents, Headache 47 (2007), pp. 1189–1194.

63. A Pakalnis, M Splaingard, D Splaingard, D Kring and A Colvin, Serotonin effects on sleep and emotional disorders in adolescent migraine, Headache 49 (2009), pp. 1486–1492.

64. O Bruni, P Febrizi, S Ottaviano, F Cortesi, F Giannotti and V Guidetti, Prevalence of sleep disorders in childhood and adolescence with headache: a case-control study, Cephalalgia 17 (1997), pp. 492–498.

65. U Isik, RH Ersu and P Ay et al., Prevalence of headache and its association with sleep disorders in children, Pediatr Neurol 36 (2007), pp. 146–151.

66. ME Luc, A Gupta, JM Birnberg, D Reddick and MH Kohrman, Characterization of symptoms of sleep disorders in children with headache, Pediatr Neurol 34 (2006), pp. 7–12.

67. A Pakalnis, C Butz, D Splaingard, D Kring and J Fong, Emotional problems and prevalence of medication overuse in pediatric chronic daily headache, J Child Neurol 22 (2007), pp. 1356–1359.

68. K Vannatta, EA Getzoff, SW Powers, RB Noll, CA Gerhardt and AD Hershey, Multiple perspectives on the psychological functioning of children with and without migraine, Headache 48 (2008), pp. 994–1004.

69. B Kroner-Herwig, L Morris and M Heinrich, Biopsychosocial correlates of headache: what predicts pediatric headache occurrence?, Headache 48 (2008), pp. 529–544.

70. RK Cady and CP Schreiber, Sinus headache: a clinical conundrum, Otolaryngol Clin North Am 37 (2004), pp. 267–288.

71. CP Schreiber, S Hutchinson, CJ Webster, M Ames, MS Richardson and C Powers, Prevalence of migraine in patients with a history of self-reported or physician-diagnosed “sinus” headache, Arch Intern Med 164 (2004), pp. 1769–1772.

72. RC Packard and LP Ham, Pathogenesis of posttraumatic headache and migraine: a common headache pathway?, Headache 37 (1997), pp. 142–152.

73. S Solomon, Posttraumatic migraine, Headache 38 (1998), pp. 772–778.

74. P Scagni and R Pagliero, Headache in an Italian pediatric emergency department, J Headache Pain 9 (2008), pp. 83–87.

75. MC Wilson and SJ Krolczyk, Pediatric post-traumatic headache, Curr Pain Headache Rep 10 (2006), pp. 387–390.

76. M Fujita, J Fujiwara, T Maki, K Shibasaki, M Shigeta and J Nii, Pediatric chronic daily headache associated with school phobia, Pediatr Int (2009).

77. D Lewis, S Ashwal, A Hershey, D Hirtz, M Yonker and S Silberstein, Practice Parameter: Pharmacological treatment of migraine headache in children and adolescents: Report of the American Academy of Neurology Quality Standards Subcommittee and the Practice Committee of the Child Neurology Society, Neurology 63 (2004), pp. 2215–2224.

78. R Fernandes, JJ Ferreira and C Sampaio, The placebo response in studies of acute migraine, J Pediatr 152 (2008), pp. 527–533.

79. S Evers, M Marziniak, A Frese and I Gralow, Placebo efficacy in childhood and adolescence migraine: an analysis of double-blind and placebo-controlled studies, Cephalalgia 29 (2009), pp. 436–444.

80. TW Ho, X Fan, A Rodgers, CR Lines, P Winner and RE Shapiro, Age effects on placebo response rates in clinical trials of acute agents for migraine: pooled analysis of rizatriptan trials in adults, Cephalalgia 29 (2009), pp. 711–718.

81. K Ahonen, ML Hamalainen, M Eerola and K Hoppu, A randomized trial of rizatriptan in migraine attacks in children, Neurology 67 (2006), pp. 1135–1140.

82. SL Linder, NT Mathew, RK Cady, G Finlayson, G Ishkanian and DW Lewis, Efficacy and tolerability of almotriptan in adolescents: a randomized, double-blind, placebo-controlled trial, Headache 48 (2008), pp. 1326–1336.

83. JL Brandes, D Kudrow and SR Stark et al., Sumatriptan-naproxen for acute treatment of migraine: a randomized trial, JAMA 297 (2007), pp. 1443–1454.

84. TR Smith, A Sunshine, SR Stark, DE Littlefield, SE Spruill and WJ Alexander, Sumatriptan and naproxen sodium for the acute treatment of migraine, Headache 45 (2005), pp. 983–991.

85. DM Walker and SJ Teach, Emergency department treatment of primary headaches in children and adolescents, Curr Opin Pediatr 20 (2008), pp. 248–254.

86. E Conicella, U Raucci and N Vanacore et al., The child with headache in a pediatric emergency department, Headache 48 (2008), pp. 1005–1011.

87. MA Kabbouche, SW Powers and A Segers et al., Inpatient treatment of status migraine with dihydroergotamine in children and adolescents, Headache 49 (2009), pp. 106–109.

88. B Bailey and BC McManus, Treatment of children with migraine in the emergency department: a qualitative systematic review, Pediatr Emerg Care 24 (2008), pp. 321–330.

91. A Visudtibhan, V Siripornpanich and C Khongkhatithum et al., Migraine in Thai children: prevalence in junior high school students, J Child Neurol 22 (2007), pp. 1117–1120.abstract

93. M Heinrich, L Morris and B Kroner-Herwig, Self-report of headache in children and adolescents in Germany: possibilities and confines of questionnaire data for headache classification, Cephalalgia 29 (2009), pp. 864–872.abstract

94. A Akyol, N Kiylioglu and I Aydin et al., Epidemiology and clinical characteristics of migraine among school children in the Menderes region, Cephalalgia 27 (2007), pp. 781–787.abstract

111. R Burstein and FM Cutrer, The development of cutaneous allodynia during a migraine attack: Clinical evidence for the sequential recruitment of spinal and supraspinal nociceptive neurons in migraine, Brain 123 (2000), pp. 1703–1709.

112. R Burstein, D Yarnitsky, I Goor-Aryeh, BJ Ransil and ZH Bajwa, An association between migraine and cutaneous allodynia, Ann Neurol 47 (2000), pp. 614–624.

113. NT Mathew, J Kailasam and T Seifert, Clinical recognition of allodynia in migraine, Neurology 63 (2004), pp. 848–852.

114. M Jakubowski, S Silberstein, A Ashkenazi and R Burstein, Can allodynic migraine patients be identified interictally using a questionnaire?, Neurology 65 (2005), pp. 1419–1422.

115. A Ashkenazi, S Silberstein, M Jakubowski and R Burstein, Improved identification of allodynic migraine patients using a questionnaire, Cephalalgia 27 (2007), pp. 325–329.

116. ME Bigal, S Ashina and R Burstein et al., Prevalence and characteristics of allodynia in headache sufferers: a population study, Neurology 70 (2008), pp. 1525–1533.

117. R Burstein, B Collins and M Jakubowski, Defeating migraine pain with triptans: a race against the development of cutaneous allodynia, Ann Neurol 55 (2004), pp. 19–26.

118. R Burstein and M Jakubowski, Analgesic triptan action in an animal model of intracranial pain: a race against the development of central sensitization, Ann Neurol 55 (2004), pp. 27–36.

119. M Jakubowski, D Levy, I Goor-Aryeh, B Collins, Z Bajwa and R Burstein, Terminating migraine with allodynia and ongoing central sensitization using parenteral administration of COX1/COX2 inhibitors, Headache 45 (2005), pp. 850–861.

120. JW Varni, M Seid and PS Kurtin, PedsQL 4.0: reliability and validity of the Pediatric Quality of Life Inventory version 4.0 generic core scales in healthy and patient populations, Med Care 39 (2001), pp. 800–812.

121. SW Powers, SR Patton, KA Hommel and AD Hershey, Quality of life in childhood migraines: clinical impact and comparison to other chronic illnesses, Pediatrics 112 (2003), pp. e1–e5.

122. SW Powers, SR Patton, KA Hommel and AD Hershey, Quality of life in paediatric migraine: Characterization of age-related effects using PedsQL 4.0, Cephalalgia 24 (2004), pp. 120–127.

123. D Kernick, D Reinhold and JL Campbell, Impact of headache on young people in a school population, Br J Gen Pract 59 (2009), pp. 678–681.

124. G Khurana Hershey, M Stevenson, E Grube and A Hershey, Characterization of headache presenting to a tertiary allergy clinic, Cephalalgia 25 (2005), pp. 1004–1005 (abstract)..

125. O Bruni, PM Russo, R Ferri, L Novelli, F Galli and V Guidetti, Relationships between headache and sleep in a non-clinical population of children and adolescents, Sleep Med 9 (2008), pp. 542–548.

126. SW Powers, DK Gilman and AD Hershey, Headache and psychological functioning in children and adolescents, Headache 46 (2006), pp. 1404–1415.

127. K Vannatta, EA Getzoff and DK Gilman et al., Friendships and social interactions of school-aged children with migraine, Cephalalgia 28 (2008), pp. 734–743.

128. SJ Wang, JL Fuh, KD Juang and SR Lu, Migraine and suicidal ideation in adolescents aged 13 to 15 years, Neurology 72 (2009), pp. 1146–1152.

129. JC Cuvellier, A Fily, S Joriot, JM Cuisset and L Vallee, French general practitioners' management of children's migraine headaches, Headache 47 (2007), pp. 1282–1292.

130. ML Hamalainen, K Hoppu, E Valkeila and P Santavuori, Ibuprofen or acetaminophen for the acute treatment of migraine in children: a double-blind, randomized, placebo-controlled, crossover study, Neurology 48 (1997), pp. 103–107.

131. DW Lewis, D Kellstein and G Dahl et al., Children's ibuprofen suspension for the acute treatment of pediatric migraine, Headache 42 (2002), pp. 780–786.

132. S Evers, A Rahmann and C Kraemer et al., Treatment of childhood migraine attacks with oral zolmitriptan and ibuprofen, Neurology 67 (2006), pp. 497–499.

133. P Winner, SL Linder, RB Lipton, M Almas, B Parsons and V Pitman, Eletriptan for the acute treatment of migraine in adolescents: results of a double-blind, placebo-controlled trial, Headache 47 (2007), pp. 511–518.

134. P Winner, D Lewis, WH Visser, K Jiang, S Ahrens and JK Evans, Rizatriptan 5 mg for the acute treatment of migraine in adolescents: a randomized, double-blind, placebo-controlled study, Headache 42 (2002), pp. 49–55.

135. WH Visser, P Winner and K Strohmaier et al., Rizatriptan 5 mg for the acute treatment of migraine in adolescents: results from a double-blind, single-attack study and two open-label, multiple-attack studies, Headache 44 (2004), pp. 891–899.

136. ML Hamalainen, K Hoppu and P Santavuori, Sumatriptan for migraine attacks in children: a randomized placebo-controlled study. Do children with migraine respond to oral sumatriptan differently from adults?, Neurology 48 (1997), pp. 1100–1103.

137. P Winner, AD Rothner, JD Wooten, C Webster and M Ames, Sumatriptan nasal spray in adolescent migraineurs: a randomized, double-blind, placebo-controlled, acute study, Headache 46 (2006), pp. 212–222.

138. P Winner, D Rothner and J Saper et al., A randomized, double-blind, placebo-controlled study of sumatriptan nasal spray in the treatment of acute migraine in adolescents, Pediatrics 106 (2000), pp. 989–997.

139. K Ahonen, ML Hamalainen, H Rantala and K Hoppu, Nasal sumatriptan is effective in treatment of migraine attacks in children: a randomized trial, Neurology 62 (2004), pp. 883–887.

140. MA Ueberall and D Wenzel, Intranasal sumatriptan for the acute treatment of migraine in children, Neurology 52 (1999), pp. 1507–1510.

141. JT MacDonald, Treatment of juvenile migraine with subcutaneous sumatriptan, Headache 34 (1994), pp. 581–582.

142. SL Linder, Subcutaneous sumatriptan in the clinical setting: the first 50 consecutive patients with acute migraine in a pediatric neurology office practice, Headache 36 (1996), pp. 419–422.

143. AD Rothner, W Wasiewski, P Winner, D Lewis and J Stankowski, Zolmitriptan oral tablet in migraine treatment: high placebo responses in adolescents, Headache 46 (2006), pp. 101–109.

144. DW Lewis, P Winner, AD Hershey and WW Wasiewski, Efficacy of zolmitriptan nasal spray in adolescent migraine, Pediatrics 120 (2007), pp. 390–396.

145. L Richer, L Graham, T Klassen and B Rowe, Emergency department management of acute migraine in children in Canada: a practice variation study, Headache 47 (2007), pp. 703–710.

146. DW Lewis, S Diamond, D Scott and V Jones, Prophylactic treatment of pediatric migraine, Headache 44 (2004), pp. 230–237.

147. D Gillies, M Sills and I Forsythe, Pizotifen (Sanomigran) in childhood migraine. A double-blind controlled trial, Eur Neurol 25 (1986), pp. 32–35.

148. PA Battistella, R Ruffilli and R Cernetti et al., A placebo-controlled crossover trial using trazodone in pediatric migraine, Headache 33 (1993), pp. 36–39.

149. G Apostol, RK Cady and GA Laforet et al., Divalproex extended-release in adolescent migraine prophylaxis: results of a randomized, double-blind, placebo-controlled study, Headache 48 (2008), pp. 1012–1025.

150. GS Miller, Efficacy and safety of levetiracetam in pediatric migraine, Headache 44 (2004), pp. 238–243.

151. A Pakalnis, D Kring and L Meier, Levetiracetam prophylaxis in pediatric migraine—an open-label study, Headache 47 (2007), pp. 427–430.

152. D Lewis and E Paradiso, A double-blind, dose comparison study of topiramate for prophylaxis of basilar-type migraine in children: a pilot study, Headache 47 (2007), pp. 1409–1417.

153. CV Lakshmi, P Singhi, P Malhi and M Ray, Topiramate in the prophylaxis of pediatric migraine: a double-blind placebo-controlled trial, J Child Neurol 22 (2007), pp. 829–835.

154. A Pakalnis and D Kring, Zonisamide prophylaxis in refractory pediatric headache, Headache 46 (2006), pp. 804–807.

155. WI Forsythe, D Gillies and MA Sills, Propanolol (‘Inderal’) in the treatment of childhood migraine, Dev Med Child Neurol 26 (1984), pp. 737–741.

156. J Ludvigsson, Propranolol used in prophylaxis of migraine in children, Acta Neurol Scand 50 (1974), pp. 109–115.

157. K Olness, JT MacDonald and DL Uden, Comparison of self-hypnosis and propranolol in the treatment of juvenile classic migraine, Pediatrics 79 (1987), pp. 593–597.

158. M Sills, P Congdon and I Forsythe, Clonidine and childhood migraine: a pilot and double-blind study, Dev Med Child Neurol 24 (1982), pp. 837–841.

159. M Sillanpaa, Clonidine prophylaxis of childhood migraine and other vascular headache. A double blind study of 57 children, Headache 17 (1977), pp. 28–31.

160. F Sorge, R De Simone, E Marano, M Nolano, G Orefice and P Carrieri, Flunarizine in prophylaxis of childhood migraine. A double-blind, placebo-controlled, crossover study, Cephalalgia 8 (1988), pp. 1–6.

161. PA Battistella, R Ruffilli and R Moro et al., A placebo-controlled crossover trial of nimodipine in pediatric migraine, Headache 30 (1990), pp. 264–268.

162. M Condo, A Posar, A Arbizzani and A Parmeggiani, Riboflavin prophylaxis in pediatric and adolescent migraine, J Headache Pain 10 (2009), pp. 361–365.

163. F Wang, SK Van Den Eeden, LM Ackerson, SE Salk, RH Reince and RJ Elin, Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a randomized, double-blind, placebo-controlled trial, Headache 43 (2003), pp. 601–610.

164. R Oelkers-Ax, A Leins and P Parzer et al., Butterbur root extract and music therapy in the prevention of childhood migraine: an explorative study, Eur J Pain 12 (2008), pp. 301–313.

165. J Ludvigsson, Propranolol used in prophylaxis of migraine in children, Acta Neurol Scand 50 (1974), pp. 109–115.

166. B Levinstein, A comparative study of cyproheptadine, amitriptyline, and propranolol in the treatment of adolescent migraine, Cephalagia 11 (1991), pp. 122–123.

167. G Serdaroglu, E Erhan and H Tekgul et al., Sodium valproate prophylaxis in childhood migraine, Headache 42 (2002), pp. 819–822.

168. P Winner, EM Pearlman, SL Linder, DM Jordan, AC Fisher and J Hulihan, Topiramate for migraine prevention in children: a randomized, double-blind, placebo-controlled trial, Headache 45 (2005), pp. 1304–1312.

169. D Lewis, P Winner and J Saper et al., Randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of topiramate for migraine prevention in pediatric subjects 12 to 17 years of age, Pediatrics 123 (2009), pp. 924–934.

170. G Apostol, DW Lewis and GA Laforet et al., Divalproex sodium extended-release for the prophylaxis of migraine headache in adolescents: results of a stand-alone, long-term open-label safety study, Headache 49 (2009), pp. 45–53.

171. G Apostol, A Pakalnis and GA Laforet et al., Safety and tolerability of divalproex sodium extended-release in the prophylaxis of migraine headaches: results of an open-label extension trial in adolescents, Headache 49 (2009), pp. 36–44.

172. A Unalp, N Uran and A Ozturk, Comparison of the effectiveness of topiramate and sodium valproate in pediatric migraine, J Child Neurol 23 (2008), pp. 1377–1381.

173. R Pothmann and U Danesch, Migraine prevention in children and adolescents: results of an open study with a special butterbur root extract, Headache 45 (2005), pp. 196–203.

174. SW Powers and F Andrasik, Biobehavioral treatment, disability, and psychological effects of pediatric headache, Pediatr Ann 34 (2005), pp. 461–465.

175. C Cottrell, J Drew, J Gibson, K Holroyd and F O'Donnell, Feasibility assessment of telephone-administered behavioral treatment for adolescent migraine, Headache 47 (2007), pp. 1293–1302.

176. M Connelly, MA Rapoff, N Thompson and W Connelly, Headstrong: a pilot study of a CD-ROM intervention for recurrent pediatric headache, J Pediatr Psychol 31 (2006), pp. 737–747.

177. E Trautmann and B Kroner-Herwig, A randomized controlled trial of Internet-based self-help training for recurrent headache in childhood and adolescence, Behav Res Ther 48 (2010), pp. 28–37.

178. T Eidlitz-Markus, Y Haimi-Cohen, D Steier and A Zeharia, Effectiveness of nonpharmacologic treatment for migraine in young children, Headache (2009) 10.1111/j.1526-4610.2009.01534.x published online Oct 5..

179. P Brna, J Dooley, K Gordon and T Dewan, The prognosis of childhood headache: a 20-year follow-up, Arch Pediatr Adolesc Med 159 (2005), pp. 1157–1160.

180. MA Kabbouche, SW Powers and AL Vockell et al., Outcome of a multidisciplinary approach to pediatric migraine at 1, 2, and 5 years, Headache 45 (2005), pp. 1298–1303.

181. JA Charles, BL Peterlin, AM Rapoport, SL Linder, MA Kabbouche and FD Sheftell, Favorable outcome of early treatment of new onset child and adolescent migraine-implications for disease modification, J Headache Pain 10 (2009), pp. 227–233.

Key sources:

[193]

193. Hershey AD. Current approaches to the diagnosis and management of paediatric migraine. Lancet Neurol 2010 Feb; 9(2) 190-204. doi:10.1016/S1474-4422(09)70303-5 pmid:20129168.

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