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HEADACHE CURRENTS: REVIEW

Pediatric Headache: A Clinical Reviewhead_2086 333..339

Howard Jacobs, MD; Jack Gladstein, MD

In this review we describe the epidemiology, classification, andapproach to the diagnosis and treatment of episodic and chronicmigraine in children. We review both traditional and alternativemedications, and offer a glimpse into the future of pediatricheadache.

Key words: migraine, headache, pediatrics

INTRODUCTIONTreatment for pediatric headache merges all that we have learnedabout adult headache with the expertise of working with chil-dren. Most adults who suffer with headaches have their firstheadaches during childhood or adolescence. Criteria for classifi-cation in children have been modified to reflect the shorterduration of pediatric migraine, but otherwise derive much of itsstructure from systems devised for adults. Because there havebeen so few successful drug trials in children, we are forced toprescribe medications tested in adults, borrowing from the troveof information we have learned from the adult literature.

The environment of a child’s world includes school, home,and community. All of these areas have profound influences onheadache. We hope to share similarities and subtle differencesthat will help our readers to better understand pediatric headacheand to be more comfortable with the childhood headachesufferer.

EPIDEMIOLOGYThough not as commonly addressed as headache in adults, thereare in fact a large number of children affected by primary head-ache disorders.1 Using the International Classification of Head-ache Disorders, 2nd edition (ICHD II) criteria, which may infact be overly strict for the pediatric population, Abu-Arafehet al2 state that the prevalence of headache in children up to 20years of age is at approximately 58% with a 1.5/1 female to maleratio. They further state the incidence of migraine headaches inthis population at 7.7%; 9.7% in females, and 6.0% in malesthroughout the age range. It has been well documented previ-ously that in the younger children, boys tend to have moremigraines than girls, but that this reverses at puberty and the

aforementioned article’s data support this.1 Geographically, thereseems to be more migraine in the Middle East and Europe and abit less in the Far East and the USA. Whether this is a truedifference or a difference in regional reporting is unclear.2

CLASSIFICATION SCHEMARather than use ICHD II classification,3 we use a more practicalapproach to pediatric headache proposed by Rothner.4 In hispaper, he classifies all pediatric headaches into 4 patterns that areeasily distinguishable from each other. Patterns can be ascertainedin seconds, so that differential diagnosis is short for each category.In acute headache, there is no antecedent. The headache justappears. In this category, viral syndromes, bacterial infections,and subarachnoid hemorrhage can present as acute headache.Headaches in this category are not usually difficult to diagnose.Acute recurrent headache, Rothner’s next category, is the one wedeal with most often. Migraine and tension-type headache fallinto this category. Children rarely get cluster headache, so wewon’t include it here. Rothner’s third pattern is termed chronicand progressive. In this pattern, headaches get worse over time.Brain tumors and benign intracranial hypertension (pseudotu-mor) fit into this group. Finally, chronic nonprogressive head-aches include chronic daily headache. These can be as a result ofevolution from episodic tension or migraine, or can arise de novoas new daily persistent headache.

There are older pediatric classification schema proposed byVahlquist5 and Prensky,6 but they have fallen out of favor for lackof quantifiable criteria, using words like “often, frequent andrare.” The ICHD criteria are easier to use for research purposes,because they employ numbers of headache and time require-ments. For the purpose of drug trials, adult criteria are used inmost pediatric studies, but they don’t account for the shorterduration of pediatric migraine, the absence of unilateral headachein most children, and the inability of most children to describeheadache using words like “throbbing.”7

As in adults, there are pitfalls to avoid in diagnosing headachein children and adolescents. Location of pain in the cheek areascan often be misconstrued as sinusitis. In acute sinusitis, theremay be fever, night cough, and bad breath. Migraine with itsintermittent pattern, autonomic symptoms, and the need to restcan sometimes involve branch 2 of the trigeminal nerve, leadingto fullness and tenderness over the maxillary sinus area. They areeasily distinguishable if one remembers that pattern is moreimportant than location. Similarly, involvement of pain in theneck area can still be migraine if the pattern is migrainous.Because posterior fossa tumors often present with neck pain,clinicians often will scan youngsters with neck pain, only to findit to be migraine.8,9 The younger the child is, the more atypical

From the University of Maryland, Department of Pediatrics, Pediatric Headache Clinic, Balti-more, MD, USA.

Address all correspondence to Drs. Gladstein and/or Jacobs, 22 S. Greene Street, N5E20,Baltimore, MD 21201.Accepted for publication August 12, 2011..............Headache© 2012 American Headache Society

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the symptoms. Periodic syndromes of childhood, such as cyclicvomiting syndrome, benign paroxysmal torticollis, and benignparoxysmal vertigo present as recurrent bouts of vomiting, neckstiffness, and dizziness, respectively. Children with these condi-tions become plain migraine patients as they get older.10 Migrainein the preschool child may lack the throbbing, unilaterality, andfull-blown autonomic symptoms. As the child gets older, weoften use the “retrospectoscope” to identify first migraine that didnot meet all the features.11

As in adults, one must account for comorbidities whenapproaching the pediatric headache patient. Children with recur-rent headache can be depressed and anxious,12 have disorderedsleep,13,14 and tendencies to be dizzy.15 They may have eatingdisorders,16 seizure disorders,17 obesity,18 menstrual irregulari-ties,19 or any other malady. Unique to childhood, our patientsspend 6-8 hours a day in school. Children struggling to learn,dealing with bullying or separation anxiety, provide unique chal-lenges to the clinician. Home should be a safe place.20 Youngstersmay be dealing with abuse, divorce, or the death of a cherishedgrandparent. Some are overscheduled and are under immensepressure, either self or parentally induced. Eating breakfast,getting enough regular sleep and regular exercise are habits thatneed to be started in the younger years.21

DIAGNOSIS AND MANAGEMENTUsing Rothner’s categories, it is possible to make a rapid diag-nosis for most children presenting with headaches. For acuterecurrent headaches, if there are autonomic symptoms (nausea,vomiting, light and sound sensitivity) and need to rest, the diag-nosis is migraine. Location of pain and duration is not veryimportant. If there never are autonomic symptoms, it is calledtension-type headache. As in adults, a childhood migraine suf-ferer can have milder headaches without autonomic features. Wemust remember this when stressing early treatment. Acute head-ache warrants worry if concern for subarachnoid hemorrhage ishigh. Instant severe headache can be the harbinger of a sentinelbleed. Chronic progressive headache warrants a magnetic reso-nance imaging (MRI) even in the absence of focal neurologicalsigns or symptoms. Patients with chronic nonprogressiveheadache come in with normal MRIs and may have seen otherproviders without success. There is no role for electroencephalo-grams (EEG) or skull films. Computerized tomography (CT) isonly indicated when time is of the essence. When suspectingsubarachnoid hemorrhage, it is important to get the patient tothe neurosurgeon as soon as possible, so an hour in an MRImachine is way too long. There is no routine blood work for aheadache work-up. If one suspects a thyroid problem, a drugissue, metabolic issue or pregnancy, a guided specific test can beordered. Again, MRI is indicated for some acute headache, thechronic progress pattern and the chronic nonprogressive pattern.Of course, if there is focality on neuro exam, an MRI must bedone.22,23

There are unique considerations when approaching childrenand adolescents with headache. When taking the history, we needto know if there are relatives with migraine. Because half of adultswith migraine don’t know it, we must ask if there is a familyhistory of headache, then ask the parent to describe. Often, wehelp discover other family members who have previously undi-agnosed migraine.24,25

What kind of headache burden has this youngster endured?How many days of school have been missed (absenteeism)? Havethe grades dropped because of headache? How many days doesthe youngster go to school but cannot learn because her headhurts (presenteeism)? Are there after-school activities that havebeen abandoned because of headache?26 Is the youngster anxiousor depressed? Does (s)he put undue pressure on him/herself? Is(s)he overscheduled? Has there been a history of separationanxiety or school phobia? Is there bullying involved? Has theyoungster struggled with an undiagnosed learning disability?27

Most importantly, we must acknowledge the youngster’s pain asreal. Often times, pediatric migraineurs are told by teachers,friends, and well-meaning relatives that they don’t really haveheadache pain, and it isn’t that bad. By acknowledging theyoungster’s pain, we form a therapeutic triad between the young-ster, the family, and the clinician.28

When treating adolescents, one must additionally considerthe child’s cognitive developmental stage. An early adolescentthinker may not understand abstract instructions and may needconcrete examples of when and how to take medications. As ateen matures (s)he may be able to use more abstract reasoningand concepts, may want to take more control of the situation,may appreciate direct access to the provider and to prescrip-tions. Issues of parental conflict may play out in the office.Empowering the more mature teen to be responsible for herheadaches may be the first step in a successful doctor–patientrelationship.29

We stress the avoidance of secondary gain in the form of schoolabsence, waking up late, or neglect of family chores and respon-sibilities. Part of the plan is to cut back the frequency and severityof the headaches, treat the headaches early, and get the youngsterback to full participation at school and at home. Expectingself-efficacy is a major part of a successful headache plan. Chil-dren with a serious headache problem need an armamentariumof skills that include relaxation hypnosis or biofeedback that theycan use to prevent headache and treat acute attacks. Whether athome or in school, teens should be allowed to ask for immediateaccess to medication when a headache hits. Healthy habits thatinclude regular sleep, exercise, fluids, and meals become a cor-nerstone of treatment.

Interviewing the adolescent with headaches can be tricky. Byexcusing the parents at the beginning, we can miss key points offamily history and miss out on the parent–child interaction. Bykeeping the parent(s) and patient together the whole time, sen-sitive issues have a tendency to be skirted. A combination works

Headache Currents334 | Headache | February 2012

best, where all are together at the beginning, while questions aremostly asked to the patient. If the parent won’t let the patienttalk, we know we have a problem. The parent can help us withfamily history and express his/her concerns. The child is affordedtime alone, often before the physical exam. All are brought backtogether at the end to hear the summary, and for the youngster toget empowered to own the problem and solution. Parentsbecome helpers rather than enablers, prescriptions are handed tothe youngster, lifestyle modifications are negotiated, and criteriafor when to contact the office are established.

TREATMENT PRINCIPLESWhether a patient has migraine or chronic daily headache treat-ments, principles are similar.

1. Incorporate healthy habits to include eating breakfast,getting consistent sleep, exercise, and hydration.

2. Employ methods to cope with stress.3. Treat attacks early to prevent chronification.4. Treat attacks with high doses to combat gastroparesis.5. Insist on school attendance.6. Allow patient to participate in his/her care.7. For patients with chronic headache and migraine

spikes, treat the migraine spikes with migraine specificmedication.

8. For those who require chronic medication, start slow andincrease dose until either desired effect is achieved or thereare troublesome side effects.

9. Pick a prevention medication that addresses comorbidity.10. Realistic expectations dictate that change that will happen

over months, not days.

ACUTE TREATMENTSMigraine responds to almost any pain medicine when caughtearly. Evidence for the use of ibuprofen and acetaminophen inchildhood exists.30,31 Triptans have been used safely for years inpediatrics,32-36 but only almotriptan (6.25 mg, 12.5 mg) hasFood and Drug Administration (FDA) approval.37 Reasons forlack of FDA approval have been reviewed by Lewis et al, whosuggests that combination of a different study design with

pediatric-friendly consents would help demonstrate a lowerplacebo rate in pediatric studies.38

ADJUNCTIVE THERAPIESOften triptans, ergotamines, and non-steroidal anti-inflammatory drugs (NSAIDs) are not enough for the acutemigraine sufferer. Gastroparesis often complicates therapy, delay-ing absorption of therapeutic agents. Most of our patients arecomplaining of nausea with their attacks. Anxiety may either beresultant to the misery being suffered or may be a pre-existingcomorbidity as discussed previously. As such, these may all needto be addressed in the acute setting. Promotility agents, anti-emetics, and anxiolytics may be necessary. Prochlorperazine,chlorpromazine promethazine, and metoclopramide have beenshown to relieve the nausea, while also showing therapeutic effectagainst the migraine itself (Table 1).39-41 While decreasing anxietymay not address the underlying pathophysiology of a migraine,an anxiolytic can decrease suffering.

EMERGENCY ROOM MANAGEMENTOF MIGRAINEEmergency rooms are terrible places for migraineurs. There canbe little worse than the noise, bright lights, frenetic activity, andconstant intrusions characteristic of an emergency department(ED) for someone suffering a migraine. However, there are timeswhen our patients end up there, either as a first presentation orwhen good management at home is unsuccessful.

As far back as 1967, and again in 1986, the use of steroids hasbeen advocated for intractable migraine.42,43 In 1986, Raskinshowed that dihydroergotamine could be used to treat intractablemigraine.44 Magnesium for emergency treatment of migraine wasshown to be effective in 1996.45 In 2000, valproate was studied inthis setting with positive results.46 More recently, Kabbouche et alshowed good response in the pediatric population to a combina-tion of ketorolac and metoclopramide.47

We have adapted what is known in the literature into a pro-tocol using a sequential administration of metoclopramide,methylprednisolone, dihydroergotamine (DHE) 45, Ketorolac,

Table 1.—Promotility Agents and Dosing

Dose Range Dosing Interval (hour) Notes

Chlorpromazine 0.55 mg/kg/day IV/IM Q6-8 6 months-5 years max 40 mg, >5 years max 75 mgMetoclopromide 1 mg-2 mg/kg/dose IV Q2-4Prochlorperazine 2.5 mg-5 mg PO Q6-Q12Promethazine .25-1 mg/kg PO/IV/IM Q4-6

IM = intramuscular; IV = intravenous; PO = orally.


magnesium sulfate, and valproate. The safety and efficacy of ourprotocol are currently being studied.

CHRONIC TREATMENTSAfter suggesting lifestyle changes and early intervention, therewill still be youngsters struggling to deal with their headacheburden. For those who have demonstrated persistent disabilitythrough either Pediatric Migraine Disability Assessment Score(PedMIDAS) or persistent school absence, prevention in theform of medications and/or complementary methods should beemployed. We discuss complementary therapies later.

There are few well-designed studies in pediatrics for use ofmedication in chronic headache.48 Therefore, clinical expertiseand consensus help guide us when selecting the right approach.Recently, topiramate at 100 mg a day has been shown to beeffective compared with placebo.49 Studies using amitriptyline50

and propranolol51,52,53 had conflicting results. Cyproheptadinehas been studied as well. Its use is often limited by somnonlenceand weight gain as troublesome side effects.54 For those patientswho choose to use chronic medicine, choose a medication thatwill address comorbidity. For example, reach for amitriptyline ifa patient has sleep problems. Topiramate would be a good choicefor an obese patient.55 Gabapentin or pregabalin might help fora patient with fibromyalgia.56 For a markedly depressed patient,however, the doses of tricyclic will not treat depression so use aselective serotonin reuptake inhibitor (SSRI) combined with adrug from a different class, such as topiramate or gabapentin.Propranolol should not be used for the depressed, asthmaticpatient, or athlete.57 Cyproheptadine58 or a tricyclic antidepres-sant59 would help one gain weight. Valproate, gabapentin, andtopiramate are anticonvulsants, so they could help a patient withmigraine and epilepsy.60 Valproate is helpful in conduct disorder,so it could help a person with violent tendencies.61 For specificdosing recommendations for these medications, please seeTable 2.

ALTERNATIVE THERAPIESAlternative (non-pharmacologic) approaches to headache careneed to be utilized in our armamentarium of care. These will bedivided here into 2 groups, behavioral therapies (self-hypnosisand biofeedback methods) and acupuncture. In a retrospective,self-reporting study, self-hypnosis was shown in a group of 144children with chronic daily headache to decrease headache occur-rence from 4.5 per week to 1.4 week.62 Nestoriuc and Martin’smeta-analysis of biofeedback studies showed positive effects ofthis modality.63 In our practice, we utilize an expert in relaxationtherapy who has helped many of our older patients.

In a retrospective, self-reporting study of 47 pediatric painsufferers, of which seven complained of migraine pain, acupunc-ture treatment was found to be “pleasant and helpful.”64 A studyof physiologic response in adults was suggestive but certainly notdefinitive of a positive effect.65 Whether this reflects a differencein the patient populations or that the pediatric population has abetter response is unclear. Further studies are warranted, but it isstill worth considering if acupuncture is available in your area.

NUTRACEUTICALSMany of our patients and their families are interested in pur-suing alternate pathways for the care of their migraines. Nutra-ceuticals are often turned to as a more “natural” alternative totraditional therapies. Alone and in combination, magnesium,riboflavin, coenzyme Q10, and the herbal extracts of butterbur,feverfew, and ginkolide B have all been suggested as preventa-tives for migraine. It is postulated that intracellular magnesiummay be decreased in migraineurs, resulting in a decreasedmigraine threshold through a number of interdependent path-ways.66 Riboflavin is a precursor for flavin compounds necessaryfor mitochondrial oxidation, which may be impaired inmigraineurs.67 Coenzyme Q10 is necessary for electron trans-port, exhibits anti-inflammatory properties, and has beenshown to be protective against glutamate toxicity, which isthought to play a key role in the pathogenesis of migraine.Butterbur extract (Petasites) has antispasmodic, anti-inflammatory, and vasodilator properties.68 Feverfew may be aserotonin inhibitor,66 and ginkolide is thought to be a platelet-activating factor antagonist and may act as a free-radicalscavenger.69

Although pediatric studies could not be found on the use offeverfew, there are a limited number of pediatric studies using theother nutraceuticals mentioned. Pothman et al, in an open-labelstudy of butterbur extract (25 mg-50 mg twice daily), showed81.6% improvement.70 Riboflavin was studied in the pediatricpopulation with equivocal results at 40 mg/day,67 but at 200 mg-400 mg/day, 68% of patients had a 50% reduction of headachefrequency and a 21% decrease in intensity.71 Tepper’s review ofalternative treatments cites a few studies which produced equivo-cal results with magnesium treatment in the pediatric popula-tion.72 Combinations of ginko, coenzyme Q10, riboflavin, and

Table 2.—Medications for Headache Prophylaxis in Chronic

Migraine

Dose Range(mg)

DosingFrequency Target

Amitriptyline 10-100 QD

Titrate to effect

Cyproheptadine 2-18 QDGabapentin 300-1200 TIDPregabalin 75-225 BIDPropranolol 40-120 BIDTopiramate 25-100 BIDValproate 80-240 TID

BID = twice daily; QD = daily; TID = three times a day.


magnesium have been studied in children and adolescentswith positive outcomes.69,73 For the family who prefers a morenatural approach, these products may offer a reasonablealternative.67-69,71,73-75

Though pediatric placebo-controlled, double-blinded studieshave yet to be done, based on the actions of each of its compo-nents, Children’s MigreLief (Akeso), a combination of 25 mg offeverfew, 90 mg of magnesium, and 100 mg of riboflavin, to betaken 1 tablet twice daily may warrant consideration as a nutra-ceutical addition to one’s migraine armamentarium.

MEASURING SUCCESSFor acute migraine, outcome is usually measured as improvementfrom moderate/severe to mild/none. For chronic headache, arbi-trary measures such as decrease in number of headaches permonth neglect functional disability. As clinicians and researchers,we want relevant end-points that reflect real-life improvement inthe day to day lives of our patients.

How do we achieve uniformity and consistency in our evalu-ation and therapy of our patients? A standardized tool must beutilized. In 1999, the Migraine Disability Score (MIDAS) wasdeveloped.76 This easy-to-use 5-item questionnaire was quicklyaccepted as a means of diagnosing and following adult headachepatients. Its usefulness in pediatrics was, however, limited. In2001, Hershey et al developed the pedMIDAS based on theMIDAS but utilizing 6 questions, 3 addressing school attendanceand functioning, and 3 evaluating participation in events outsideof school.77 The questionnaire is based on the patient’s recall ofthe previous 3 months and can be used longitudinally to assessresponse.

General use of the pedMIDAS will allow easier reviewof therapeutic modalities across centers by standardizing theevaluative process used, potentially hastening the lengthyprocess to evaluate treatments for approval in our patientpopulation.

ON THE HORIZONBotulinum toxin type A (Botox) has received a lot of attention asthe only approved medication for chronic migraine in adults. Ina small study in adolescents, Chan et al. showed that Botox hasthe potential for benefit in our patients but recommends furtherstudy.78

Other prophylactic medications not in general use butstudied in the past 10 years with positive outcomes aretizanidine,79 zonisamide,80 and memantine, an N-methyl-D-aspartate receptor antagonist.81 However, controlled studies onthese drugs in the pediatric population have not beencompleted.

New therapies for acute care include diclofenac powder,which in 2 studies was shown to be superior to bothplacebo and diclofenac tablets,82,83 and an air-injectableneedle-free formulation of sumatriptan, offering fast absorption

and distribution, which may be more attractive to thosewith a needle aversion and not require a sharps disposal.84 Soonto be available will be sumatriptan in a patch formulation,avoiding the problems with gastrointestinal absorption andinjection discomfort.85

As with almost all headache medications used in pediatrics,FDA approval will be difficult, so off-label use will be the norm.

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