Review Article

Pediatric Headache: Where Have We Been and Where Do WeNeed to Be

Samata Singhi, MD; Howard Jacobs, MD; Jack Gladstein, MD

In this article, we hope to summarize current understanding of pediatric headache. We discuss epidemiology, genetics,classification, diagnosis, outpatient, emergency and inpatient treatment options, prevention strategies, and behavioralapproaches. For each section, we end with a series of questions for future research and consideration.

Key words: pediatric headache, migraine, epidemiology, genetics, classification

(Headache 2014;54:817-829)

In all fields of medicine, new discovery could nothappen without the pioneering work of innovators.Pediatric headache has come a long way as Bo Billewrote the first descriptive article on his group of Scan-dinavian school children.We have made strides in thefields of classification, refining International Head-ache Society (IHS) criteria for pediatrics, approachesto care, drug trials, emergency room (ER) manage-ment, psychiatric care, alternative medicine, andgenetics. In each section of this article, we will high-light current thinking and project to the future withthe hope that innovations in pediatric care for theheadache patient will become a priority as we striveto improve health for our population.

HISTORIC ARTICLESBille performed an epidemiological look at

school children in Uppsala, Sweden. His oft quoted

1962 paper taught us that as children got older, theproportion of patients with nonmigrainous headachesincreased. He also found that the prevalence of head-ache was equal in boys and girls before puberty buthad a more female predominance after puberty.1

Early attempts at Classification of PediatricHeadache reflected criteria in the adult literature.Prensky2 relied upon descriptors such as throbbingand intermittent headache but did not quantify fre-quency. There was no account for severity or localiza-tion. As in the adult literature, it was very hard tocompare groups of subjects using these criteria.3 Hetaught us, however, that pediatric pain is more oftenbilateral and short-lived. This paved the way for IHSmodifications when those criteria were established.IHS I4 gave the world a uniform definition ofmigraine that allowed for better quantification ofmigraine. Criteria were for adults only, however.Using adult criteria excluded many youngsters fromdrug trials because headache duration had to be 4hours, and unilateral pain was a major criterion.Maytal and others5 modified adult criteria for chil-dren and enabled us to better diagnose migraine inchildren.

From the Pediatric Neurology, University of Maryland Schoolof Medicine, Baltimore, MD, USA.

Address all correspondence to J. Gladstein, University ofMaryland School of Medicine, Pediatric Neurology, 22 SouthGreene Street, Room n5W69, Baltimore, MD 21201, USA.

Accepted for publication February 22, 2014. Conflict of Interest: None.

ISSN 0017-8748doi: 10.1111/head.12358

Published by Wiley Periodicals, Inc.Headache© 2014 American Headache Society

817

Classification of chronic daily headache has beencontroversial in the adult literature (Silberstein et al6

vs IHS4 ). This has been reflected in the pediatricliterature as well. Attempts to modify Silberstein cri-teria by Holden et al7 then by a multicenter approachled by Koenig et al8 showed that there was less medi-cation overuse and a shorter period of transformationfrom episodic to chronic headache in children as com-pared with adults.

Approach to care has been summarized by manyof the pediatric headache experts. Excellent reviewarticles,9-12 book chapters,13 and textbooks14 give thestudent, resident, and uninitiated learner the ability toprovide competent care to children and teenagerswho suffer with headache.

Drug trials are still fraught with problems. It hasbeen difficult to show spread between placebo andstudy drug. This has made it arduous to get pediatricindications for excellent medications.15 Nevertheless,almotriptan,16 rizatriptan,17,18 eletriptan, and suma-triptan nasal have jumped those hurdles.19-21 Trials ofpreventative medications have been mostly inconclu-sive, but a topiramate trial using modern classificationcriteria was successful.22

We have learned how to evaluate and treat chil-dren and teens who come to our ERs; thanks to thework of Li et al,23 Kabbouche and Linder,24 and Lewisand Qureshi.25 What we know in this area is summa-rized recently by Gelfand and Goadsby.26

We have used the work of Holyroyd and Drew27

to help us evaluate youngsters with headache andlook for psychiatric co-morbidities. The works ofZeltzer and Schlank,28 and McGrath29 give us frame-works for self-efficacy and pain management.

Last but not the least, Hershey30 has begun study-ing genetic patterns in youngsters with headache andhopes to predict who will get better based on his orher genetics.

EPIDEMIOLOGY OF PEDIATRICHEADACHE

What We Know.—The occurrence of headacheincreases as children age. Bigal and Lipton reportedthat headache prevalence rises from 3-8% of 3-year-olds, to 57-82% of 8- to 15-year-olds. They also statethat in prepubertal children, the prevalence of

migraine is higher in boys than in girls, but afterpuberty, this trend reverses. The peak incidence ofmigraine with aura in boys is 5 years of age andmigraine without aura is 10-11 years of age. In girls,migraine with aura peaks at 12-13 years of age,whereas migraines without aura reaches a peak at14-17 years of age.31 It has been well documented thatone cannot adequately treat migraine without consid-ering the comorbid psychological problems that arepresent in a large number of our patients. A meta-analysis by Balottin et al highlights the role ofpsychopathogical factors not only in migraine butalso in tension-type headache (TTH) in children.32

What We Would Like to Know.—Why do somechildren get migraines and not others? Is it all genet-ics as discussed later in this article or are there otherfactors that need to be considered. What role doesenvironment play? Does climate have a role? Do weneed to consider housing factors, ie, environmentalcompounders such as mold and building materialssuch as insulating products? Does diet play a role notjust in the cause of an acute migraine but in the ten-dency to get migraines? Are chronic ingestions oftrace minerals or other pollutants a factor? Could thisbe one of the reasons migraines tend to run in familiesas opposed to or in addition to genetics?

What is the relationship of migraine to other ill-nesses? We are beginning to see articles suggesting apossible relationship to gastrointestinal diseases suchas inflammatory bowel disease or celiac.33 We fre-quently see postural orthostatic tachycardia syn-drome (POTS) in our patients. Are there otherillnesses that coexist in a higher frequency withmigraine, and if so, why? Is this all related to a dys-function of the autonomic nervous system?

Why do some patients progress from intermittentmigraine to chronic migraine while others do not?What could be mitigating this?

Are pediatric migraineurs destined to havemigraine as adults? Does treatment as children oradolescents have a significant effect on altering thecourse of migraine in adult life?

PATHOPHYSIOLOGYWhat We Know.—Our assumptions about the

pathophysiology of headache in youngsters stems

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directly from what we have learned in adults.Goadsby34 categorizes the elements in understandingof headache physiology into 5 areas:

1. Anatomy of head pain.2. Activation of the peripheral branches of the

opthalmic branch of the trigeminal nerve.3. The physiology and pharmacology of the trigemi-

nal nucleus.4. Central nervous system activation on association

of pain in the thalamus brainstem modulation thatcontrol our perceptions of pain.

Recent summaries by Peitrobon andMoskowitz,35 Sprenger and Magon,36 and Gaspariniet al37 highlight general physiology, functional mag-netic resonance imaging, and genetics, respectively.

What We Would Like to Know.—Why do somepeople present in childhood while others wait untiltheir 20s or 30s to have their headaches? Why dosome children present with periodic syndromes whileothers present with more typical migraine? Why ismigraine more bilateral in children than in adults?Why do children and adolescents with chronic dailyheadache evolve from episodic migraine so quickly?How does the developing brain affect this physiol-ogy? Can we alter the natural course of migraine withaggressive management? Can we prevent brainalterations that occur in the adult chronic headachesufferer if treated well in childhood?

THE GENETICS OF HEADACHEWhat We Know.—In 1996, Russell et al published

an article confirming what had long been suspected,that migraine with and without aura tend to be inher-ited diseases. First-degree relatives of patients withmigraine without aura had a 1.9-fold increase risk ofdeveloping migraine without aura, while spouses hada 1.5-fold risk. First-degree relatives of patients withmigraine with aura had a 4-fold increased risk ofmigraine with aura, while spouses had no increase inrisk.38

Familial hemiplegic migraine has been associatedwith mutations of CACNA1A on chromosome 19,39

ATP1A2 on chromosome 140 and of SCN1A on chro-mosome 2.41 Other gene mutations have been identi-

fied; the MTHFR polymorphism is increased inpatients with migraine with aura but not in patientswith migraine without aura,42 polymorphisms in theserotonin transporter gene (5HTTLPR), also associ-ated with migraine with aura.43 There are others alsoidentified.44 Amitriptyline response in depression hasbeen linked to CYP2D6 and CYP2C19 genes,45 butthis has not been studied in migraine therapy.

Hershey et al showed that there was a relationshipbetween specific blood biomarkers, which were alsopresent in brain tissue, to medication overuse head-ache suggesting a genomic association. Silberstein andDodick provide an excellent tutorial and review ofgenetics and the role of the genome in migraine thatare highly recommended to anyone wishing to learnmore on the subject.46,47

What We Would Like to Know.—There remainnumerous questions whose answers could be currentlyhidden in the genome. Why is success of drug therapyso variable? Why are medication side effects so vari-able? Can genetic markers help guide what medica-tions will be most successful in a given patient? Arethere genetic polymorphisms that predispose certainpatients to post-concussion headaches?

Is there a genetic link between migraine and otherdisorders, such as POTS, inflammatory bowel disease,celiac disease, obesity, or psychological disorders?

CLASSIFICATIONPrimary headaches in children mainly consist of

migraine, TTH, and less frequently, cluster headache.Migraines consist of acute recurrent headaches thatare usually unilateral, pulsating in nature, and may beassociated with autonomous symptoms such as pho-tophobia, phonophobia, or nausea. It is important tokeep in mind though that many younger children donot present with these classic symptoms and diagnosisis often made retrospectively. TTH is acute recurrentheadache often described as a sense of tightness orpressure, commonly suboccipital in location, withoutthe previously mentioned autonomic symptoms.

Chronic daily headache is defined as greater than15 headache days per month. There are 3 major cat-egories of chronic daily headaches in children:chronic migraine, chronic TTHs, and new daily persis-tent headache (NDPH).48 NDPH is characterized by

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the occurrence of a new headache that becomes dailywithin 3 days of onset and is not caused by anotherdisorder.

The current ICHD-II criteria/IHS 2004 Interna-tional Classification Headache Disorders49 providea detailed classification of headache; however, thisclassification captures only 61.9% of pediatricsubjects.

50,51

APPROACH TO DIAGNOSISThe approach to the youngster with headache is

similar to that of adults with headache but different ina few important areas. In both adults and children,diagnosis is usually not time-consuming. Most chil-dren presenting to a primary care office with head-ache will end up with a diagnosis of migraine.Diagnostic criteria are different, however. Childrentend to have shorter attacks and have more bilateralheadache.5

Picking out the rare patient with secondary head-ache is again similar. Patterns of progressive head-ache or chronic daily headache require scanning torule out intracranial pathology, whereas straightfor-ward migraine does not.52 Children need to grow, andadolescents need to go through puberty. Hence, arrestin growth curves or pubertal development shouldalarm the practitioner into starting a work up. Simi-larly, secondary amenorrhea is a harbinger of possiblesecondary headache.

Other important clues to diagnosis and manage-ment in youngsters include a different measure ofdisability. Whereas adults measure disability in daysof work missed or inability to do housework,53 kidsnever do housework. Grade performance and schoolabsenteeism may be better markers to follow.52 Trig-gers may be different as well. The child with an undi-agnosed learning disability or the youngster beingbullied may get better in the summer when stressdrops precipitously. Sleep hygiene is hard to enforceupon kids who start school very early. Parents in themidst of divorce present unique challenges for thechild with headaches.

Physical exam is similar but focus on growthcurves and pubertal development. Pediatricians maynot be used to looking at fundi, which makes it diffi-cult to evaluate chronic headache patients. Papill-

edema, retinal hemorrhage, or focal findings on theneurological exam suggest alternate diagnosis. Symp-toms of depression, which include sadness, tearful-ness, and withdrawal from activities need to bechecked. The presence of 1 or more of these “redflags” should make the physician consider a moreextensive evaluation.

PRINCIPLES OF TREATMENTThe initial approach to management of pediatric

headaches includes assessing triggers, identifyingcomorbidities, and establishing the degree of disabil-ity.12 A headache diary is often useful in assessingcharacteristics of headache, associated symptoms, andpossible triggers. Validated pain assessment tools orpediatric specific disability tools like the PedQL orPedMIDAS53 may be used to assess the degree ofdisability that can then be used to design treatment.In general, it is useful to get the family as well as thepatient involved, set up realistic expectations, andensure consistent follow-up.

The evidence supporting the effectivenessof any intervention – pharmacological or non-pharmacological – is confounded by the fact thatmigraines in children are of shorter duration and havea higher rate of spontaneous remission than that inadults; hence, making it difficult to distinguish effec-tiveness of treatment from the natural course of themigraine.54,55 Moreover, a high placebo response ratein children, up to 55% for prophylactic drugs and upto 69% for symptomatic treatment, has been demon-strated in children.12

OUTPATIENT ACUTE MANAGEMENTWhat We Know.—Initial symptomatic therapy for

pediatric migraine primarily consists ofacetamenophen and ibuprofen.56,57 A randomized,controlled trial in 88 children aged 4-16 years com-paring acetaminophen 15 mg/kg, ibuprofen 10 mg/kg,and placebo during 3 migraine attacks demonstratedthat acetaminophen and ibuprofen were more effec-tive than placebo at 2 hours in reduction of head-ache.58 Although multiple triptans have been studiedin the treatment of pediatric migraine,59 onlyalmotriptan and rizatriptan are approved for use inacute treatment of migraine headache in adolescents

820 May 2014

and children aged 6-17 years, respectively. In adoles-cents aged 12 and above, sumatriptan nasal spray 5,10, and 20 mg has been found to be effective for acutemigraine over placebo in the symptomatic treatmentof intensity and duration of pediatric migraine.60-64

However, nasal sumatriptan has been found to beassociated with bad taste, nausea, vomiting, burning/stinging sensations, or paresthesia and light-headedness. Oral or nasal zolmitriptan has also beenfound to be effective in treatment of migraine attacksin children aged 5-15 years.65-67 There are insufficientdata to support the efficacy of other oral triptans inthe treatment of pediatric migraine.56,65,68,69

Most TTH is managed by primary care physicianand commonly used agents include acetaminophen,ibuprofen, and aspirin.12,70,71

It has been widely postulated that medicationshould be taken shortly after onset of headache tomaximize effectiveness,48 although there is no scien-tific evidence to support this.12 Moreover, migraine isoften complicated by concomitant gastroparesis,which may necessitate higher than normal doses ofmedications to achieve desired effect. Expert opinionsuggests addition of caffeine (in soda, tea, or coffee) toan Non-steroidal Anti-inflammatory drug (NSAID)less than 9 days a month for severe headache,althoughthere are no trials demonstrating the efficacy of this.48

What We Would Like to Know.—We need largerscale, well-designed, randomized, controlled trials inchildren to establish the effectiveness of triptans asabortive agents. How do we design trials that reducethe high placebo rate? Are there combinations thatwork better than one preparation alone?

What are the potential long-term effects ofroutine use of these medications on children? Do theydevelop tolerance as they advance into adulthood?

ER AND INPATIENT MANAGEMENTWhat We Know.—Headache is one of the most

common presentations to the pediatrics ER.25 Most ofthe time, one can ferret out who has tumor, bleed, orother serious secondary headache disorder fromthose with exacerbation of migraine or chronic dailyheadache. We therefore do not advocate routine ERimaging for those patients at low risk for secondaryheadache when they present.72

There have been multiple papers describing suc-cessful approaches to treatment of status migraine inboth the emergency setting, as well as the inpatientsetting.73,74 Careful sequential use of medicationsused in the adult setting has been tried in childrenwithout a systemic prospective study.75,76 In patientsnaïve to triptans, triptans may serve as good first-lineagents after analgesics.65 As with adults who utilizethe ER for their headache exacerbations, pediatricheadache experts have shied away from the prescrib-ing of narcotics.77,78 Judicial use of Intravenous fluids,NSAIDs, dopaminergic agents, magnesium,valproate, and Dihydroergotamine (DHE) havebeen used successfully.24,65,79-83 Steroids are used asanti-inflammatory agents, and their roles in the ERsettting have been summarized well for adults.26,76

There is much experience treating adults as inpa-tients.84 There is one long-term inpatient unit atCleveland Clinic where children and adolescents withchronic headache are shown a multidisciplinaryapproach. Programs in Michigan, Chicago, and Phila-delphia incorporate teens into their adult inpatientheadache units on a regular basis. Criteria to enterthese units mirror those in the adult literature.

What We Would Like to Know.—In the future, wewould like to see a more rigorous approach with pro-spective trials of both individual agents and cocktailsto look for safety, efficacy, and ER efficiency. Whatrole does each of the components in a sequentialcocktail have? Do steroids help? What about magne-sium? Does DHE early in the pathway get people outquicker? What about IV valproate? Should young-sters be sent home on steroids and/or long-actingtriptans? How different is treating status migraine inan episodic migraineur compared with a patient withchronic daily headache and acute exacerbation?Should the approach be different? Does frequent ERuse predict debilitation as an adult?

PROPHYLAXISPharmaco-prophylaxis is usually indicated if

migraines occur at least 3-4 times a month and causesignificant impairment in the patient’s daily functionor quality of life and if lifestyle modification and non-pharmacological measures have not been effective.The goal is usually to reduce frequency of migraines

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to less than 1-2 attacks a month. The generalapproach to pharmaco-prophylaxis is to start at thelowest dose and titrate upwards as needed. Beforebeginning any preventive therapy, it is important toset realistic expectations with the patient and thefamily because any preventive therapy typically takesat least 8-12 weeks to cause a recognizable effect.12,48

What We Know.—Various agents have been tried inthe prophylaxis of pediatric migraines including tricy-clic antidepressants (amitryptiline and nortriptyline),trazodone, beta blockers (propranolol), calcium-channel blockers (verapamil and flunarizine), anti-serotonergics (cyproheptadine), gabapentin, andanti-epileptics.67

Based on Cochrane systematic review of 20 ran-domized trials, flunarizine has demonstrated efficacyin the prophylaxis of chronic pediatric migraine. Thiscompound is not available in the USA, however.67,85-88

It is associated with daytime sedation and weightgain. Administering it in early evening can avertdaytime sleepiness.12 Anti-epileptics such astopiramate at 2 mg/kg have been shown to be effec-tive for reduction of headache frequency, severity, andduration.89 Most common side effects cognitive andweight loss.12,90,91 Divalproate 15-45 mg/kg/day hasshown to be effective in reducing frequency as well asseverity of pediatric migraine with 50% headachereduction seen; side effects were dizziness, drowsi-ness, and increase in appetite.92,93

Amitryptiline,94,95 cyproheptadine,12,91 levetira-cetam,96 and zonisamide97 have been trialed success-fully in pediatric migraine, but further evidence isneeded to establish efficacy. Conflicting data exist forthe efficacy of propranolol.12,98-101 Trials have notestablished efficacy of nimodipine,102 timolol, papav-erine, pizotifen,103 trazodone,104 clonidine,105,106 meto-clopramide,67 and domperidone.67 Further research isneeded on all other agents before making any conclu-sive recommendations regarding their use for man-agement of pediatric migraine.

Before starting therapy, care must be taken toidentify potential side effects of these medicationsthat may affect certain groups of children more thanothers. For instance, valproic acid may be teratogenicand have other toxic effects and therefore may not besuited for teenage girls. Beta-blockers may not be

ideal agents for children with asthma, atopy, or ahistory of depression. At the same time, antisero-tonergics such as cyproheptadine may be particularyuseful in children with comorbid environmentalallergies.48

What We Would Like to Know.—What is differentin the pathophysiology of migraine in children requir-ing pharmacoprophylaxis from those who respond toabortive treatment? Is there something fundamentalto the perception of pain that can be addressed withpsychotherapy rather than pharmacotherapy, therebyreducing the need for medication? What specific cri-teria based on disability and risk of relapse should weuse for starting prophylactic therapy weighing itagainst the potential long-term effects of pharma-coprophylaxis (much like the asthma severity assess-ment tool used in many canters)? Prospective studiesare needed to assess what is the long-term evolutionof migraine (into adulthood) of children who are onpharmaco-prophylaxis compared with those who arenot.

BEHAVIORAL AND NUTRACEUTICALTHERAPY

In addition to the pharmaceuticals used formigraine therapy, other modalities are often calledupon. Behavioral therapies, such as biofeedback andrelaxation therapy/self-hypnosis, are often suggestedto the pediatric and adolescent migraineur, and therecontinues to be a large and possibly increasing inter-est in nutraceutical products for migraine therapy.Pistola, Sacco, and Carolei’s review (2012) state thatin the case of chronic migraine, at least, “The highestlevel of care is achieved when behavioral therapiesare integrated with other treatments, including physi-cal and pharmacological interventions.”107

What We Know.—In 2000, the US Headache con-sortium evaluated Biofeedback and graded the evi-dence supporting its use in migraine as “Grade A.”108

This evidence is often quoted in more recent articlessupporting its use.109,110 Mullally et al, however, cameto a different conclusion:

Biofeedback is an extremely costly and time-consuming modality that, in our study, providedno additional benefit when compared to simple

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relaxation techniques alone, in the treatment ofmigraine and tension type headaches in adults.111

One can find many pediatric reports supportingthe use of biofeedback,54,112-116 but the overall evi-dence is inconclusive.117-119 This begs the question, whyis biofeedback not in more widespread use? Is there alack of qualified practitioners? Is it, as suggestedearlier, not cost-effective? Many of the studies thatsupport the use of biofeedback in pediatrics alsomake a strong case for relaxation therapy.12,54

Psychotherapeutic approaches such as relaxationtechniques and cognitive behavioral therapy havebeen shown to reduce frequency and intensityof headache in children and adolescents.54,120-122

However, the overall effectiveness of psychotherapyneeds further investigation.123 In addition, musictherapy has also shown promise in the prevention ofpediatric migraine.11

Finally, there is some evidence to support prophy-laxis with lifestyle modification such as intake ofadequate amount of fluids, regular meals, mainte-nance of sleep hygiene, and exercise.12,124 There is con-flicting use for the role of diet modification such asadoption of oligo-antigenic diet.12

What We Would Like to Know.—Why is biofeed-back not a routine part of migraine care? Is biofeed-back in the pediatric population cost-effective? In thepediatric population, is biofeedback superior to relax-ation therapy or vice versa, and how do eithercompare with acupuncture? How do they comparewith more accepted pharmaceutical therapies? Howcan they best be used to augment pharmaceuticaltherapy?

NEUTRACEUTICALSWhat We Know.—Nutraceuticals such as herbals

and vitamins have always taken a back seat to phar-maceuticals in the eyes of most practitioners.However, many patients and parents are drawn to thepromise of migraine therapy with less, if any, sideeffects suggested in the nutraceutical aisle at the phar-macy. Two excellent review articles were publishedin Headache in March 2011. Sun-Edelstein andMauskop’s article on alternative headache therapy125

and Taylor’s discussion of the biological basis of

nutraceutical therapy126 are excellent sources of infor-mation on the why’s and how’s of nutraceuticaltherapy. Magnesium, coenzyme Q10, butterbur, fever-few, riboflavin, and others have a biological basis toexpect them to be efficacious in the treatment ofmigraine, and combinations such as Migravent® (VitaSciences,Airmont, NY, USA) (magnesium, riboflavin,butterbur, coenzyme Q10) and MigreLief® (AkesoHealth Sciences LLC, Westlake Village, CA, USA)(magnesium, riboflavin and feverfew), and othersshould, in theory, be helpful for our pediatricmigraineuers. But good double-blinded studies do notexist.

Magnesium oxide has been studied in children andadolescents with some evidence that it might reduceheadache severity; however, the effect on headachefrequency remains unclear.127,128 The typical adolescentdose of elemental magnesium is 350-500 mg/day. Themost common side effect of oral magnesium is diar-rhea. Coenzyme Q10 was found to be more effectivethan placebo in 1 small randomized clinical trial.129

Riboflavin 25-400 mg/day has been shown to be effec-tive in the prevention of adult migraine130,131 but hasnot been proven to be effective in migraine prophy-laxis in children.

What We Would Like to Know.—High-qualitystudies are needed comparing the variousnutraceuticals, comparing the combination productsand finally comparing nutraceuticals to more estab-lished pharmaceutical therapies, in terms of efficacy,adverse effects, and cost.

CONCLUSIONIn this review, we hope to have summarized

current knowledge and approaches for the youngsterwith headache. If we have missed key literature cita-tions, we owe an apology to those that have worked sohard to render care and grow the field of pediatricheadache. We hope to stimulate conversation andresearch collaboration as we seek answers to the chal-lenges that lie ahead. It is our sincere wish that atten-tion to pediatric headache can lessen the burden ofheadache for the youngsters that suffer now andprevent further disability down the line as theseyoungsters grow into adulthood.

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STATEMENT OF AUTHORSHIP

Category 1(a) Conception and Design

Jack Gladstein; Howard Jacobs; Samata Singhi(b) Acquisition of Data

Jack Gladstein; Howard Jacobs; Samata Singhi(c) Analysis and Interpretation of Data

Jack Gladstein; Howard Jacobs; Samata Singhi

Category 2(a) Drafting the Manuscript

Jack Gladstein; Howard Jacobs; Samata Singhi(b) Revising It for Intellectual Content

Jack Gladstein; Howard Jacobs; Samata Singhi

Category 3(a) Final Approval of the Completed Manuscript

Jack Gladstein; Howard Jacobs; Samata Singhi

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