Diff erential diagnosis: \231 Visceral hyperalgesia due to central sensitization. \231 Viscero-somatic convergence and referred pain from viscera. \231 Abdominal cutaneous nerve entrapment (ACNE). \231 Intercostal (T7 \200\223T12) or subcostal (L1) neuralgia. Further history revealed that the patient had started taking oral contraceptives for irregu lar menses at the age of 13 years. She slept over a friend \200\231s house and forgot to ta ke her pill the day before her pain developed. Her mother had a history of heavy and painfu l periods and both of her maternal aunts were diagnosed with endometriosis when they underw ent laparoscopy as part of an infertility workup. Additional history revealed that her pediatrician has suggested she meet with a psychologis t because of depressed mood and school avoidance. Th e patient started high school this yea r and has missed many days of school due to pain. She has stopped play- ing soccer and chee rleading due to pain, activities she previously enjoyed. She has withdrawn from peers and s ocial activities. Th e patient spends most her time at home resting on the couch and worryi ng about undiagnosed serious illness. She feels that some healthcare providers no longer be lieve she has pain and view her as \200\230faking. \200\231 Sleep is diffi cult to initiat e and non-restorative. She will probably have to repeat ninth grade due to absences. Th is patient was referred to an adolescent gynecologist for evaluation. With her history o f persistent abdominopelvic pain while on an oral contraceptive and positive family history of endometriosis, this patient has a high chance of being diagnosed with endometriosis. At the time of laparoscopy she was found to have stage I endometriosis. Th e surgeon procee ded to cauterize visible lesions in the abdomen and pelvis. She was treated with a continuo us oral contraceptive (without breaks or placebos for suppression of menses), and was start ed on gabapentin for treatment of the neuropathic component of her pain symptoms. Over the next 2 to 3 months, she had several episodes of painful spotting. Her pain symptoms fl ared and did not respond to NSAIDs. Her gynaecolo- gist made some changes to her hormonal thera py to improve sup- pression of ovulation. She received a prescription for tramadol 25 to 50 mg every 8 h, with instructions to take no more than 3 to 5 days during the month. Th e patient describes periumbilical and left lower quadrant pain that is present all the t ime to a variable degree. Th e pain symptoms developed gradually over the past 18 months. S he cannot recall an inciting event or illness. Th e pain is described as a sharp, stab- bin g, and sometimes throbbing sensation that comes on randomly without obvious triggers. Any t ight-fi tting clothing over her abdo- men worsens the pain. Th e pain is always present, bu t can range in intensity from 5 to 10/10 on a numerical rating scale. Th e pain is not rela ted to food intake, bowel movements, or voiding, though sometimes these activities cause pa in to increase. Pain is some- times worse with menses but can occur any time of the month. She has occasional nausea but has not vomited. Bowel and bladder patterns have not changed. She has a history of constipation and is treated with Miralax . She has an upcoming app ointment with the Pain Treatment Clinic for evaluation of new low back pain. Subsequently, with the combination of hormonal suppression, NSAIDs, gabapentin, and occasio nal tramadol, her pain symptoms subsided. She was able to return to school and began to wor k with a psychologist, and started taking an antidepressant for her mood symptoms. One mont h aft er her surgery, the patient was able to return to school for two classes a day, and w ithin 2 weeks she was attending school full time, participating in gym class, and playing s oft ball with her freshman team. She still has occasional severe cramping, but her pain is manageable on her current regimen and does not interfere with her desired activities. Past medical history is signifi cant for menarche at age 11 years. Menses are irregular and she takes an oral contraceptive pill. She is followed by GI for IBS, diagnosed at age 12 y ears with asso- ciated GERD which is treated with Prevacid and constipation, treated wit h Miralax . Previous surgeries include laparoscopic cholecystectomy and appendectomy. Fa mily history reveals that her mother and aunts had diffi culty conceiving. References Alagiri , M. , Chottiner , S. , Ratner , V. , Slade , D. , and Hanno , P. M. ( 1 997 ). Interstitial cystitis: unexplained associations with other chronic disease and pain syndromes . Urology , 49 , 52 \200\22357. On physical exam she is very anxious, lying on her right side, and crying. Vital signs: hea rt rate 93/min, regular; respiratory rate 15/min, crying; blood pressure 115/65; room air S pO 2 = 100%. American College of Obstetricians and Gynecologists. ( 2005 ). ACOG Committee Opinion. Numb er 310, April 2005. Endometriosis in adolescents . Obstet Gynecol , 105 , 921 \200\223927. CHAPTER 30 chronic pelvic pain in children and adolescents 305 Kepenekci , I. , Keskinkilic , B. , Akinsu , F. , Cakir , P. , Elhan , A. H. , Erkek , A. B . , et al . ( 2011 ). Prevalence of pelvic fl oor disorders in the female population and th e impact of age, mode of delivery, and parity . Dis Colon Rectum , 54 , 85 \200\22394. Anaf , V. , Chapron , C. , El Nakadi , I. , De Moor , V. , Simonart , T. , and No l , J. ( 2006 ). Pain, mast cells, and nerves in peritoneal, ovarian, and deep infi ltrating endo metriosis . Fertil Steril , 86 , 1336 \200\2231343. Baessler , K. , Bircher , M. D. , and Stanton , S. L. ( 2004 ). Pelvic fl oor dysfunction Klein , J. R. , and Litt , I. F. ( 1981 ). Epidemiology of adolescent dysmenorrhea . in women aft er pelvic trauma . BJOG , 111 , 499 \200\223502. Pediatrics , 68 , 661 \200\223664. Bajaj , P. , Madsen , H. , and Arendt-Nielsen , L. ( 2003 ). Endometriosis is associated wi th central sensitization: a psychophysical controlled study . J Pain , 4 , 372 \200\223380 . Kontoravdis , A. , Hassan , E. , Hassiakos , D. , Botsis , D. , Kontoravdis , N. , and Crea tsas , G. ( 1999 ). Laparoscopic evaluation and management of chronic pelvic pain during ad olescence . Clin Exp Obstet Gynecol , 26 , 76 \200\22377. Latthe , P. , Mignini , L. , Gra y , R. , Hills , R. , and Khan , K. ( 2006 ). Factors predisposing women to chronic pelvic pain: systematic review . Br Med J , 332 , 749 \200\223755. Ballard , K. D. , Seaman , H. E. , De Vries , C. S. , and Wright , J. T. ( 2008 ). Can symp tomatology help in the diagnosis of endometriosis? Findings from a national case-control st udy \200\224Part 1 . BJOG , 115 , 1382 \200\2231391. Ballweg , M. L. ( 2004 ). Impact of endometriosis on women \200\231s health: comparative hi storical data show that the earlier the onset, the more severe the disease . Best Pract Res Clin Obstet Gynaecol , 18 , 201 \200\223218. Laufer , M. , Goitein , L. , Bush , M. , Cramer , D. , and Emans , S. ( 1997 ). Prevalence of endometriosis in adolescent girls with chronic pelvic pain not responding to conventiona l therapy . J Pediatr Adolesc Gynecol , 10 , 199 \200\223202. Berkley , K. J. ( 2005 ). A life of pelvic pain . Physiol Behav , 86 , 272 \200\223280. Be rkley , K. J. , Rapkin , A. J. , and Papka , R. E. ( 2005 ). Th e pains of endometriosis . Laufer , M. , Sanfi lippo , J. , and Rose , G. ( 2003 ). Adolescent endometriosis: diagnosi s and treatment approaches . J Pediatr Adolesc Gynecol , 16 , S3 \200\22311. Science , 308 , 1587 \200\2231589. Bulun , S. E. ( 2009 ). Endometriosis . N Engl J Med , 360 , 268 \200\223279. Campo , J. V . , Di Lorenzo , C. , Chiappetta , L. , Bridge , J. , Colborn , D. K. , Gartner , J. C. , e t al . ( 2001 ). Adult outcomes of pediatric recurrent abdominal pain: do they just grow ou t of it? Pediatrics , 108 , E1 . Li , Y. , Qi , L. , Wen , J. G. , Zu , X. B. , and Chen , Z. Y. ( 2006 ). Chronic prostatit is during puberty . BJU Int , 98 , 818 \200\223821. Lubianca , J. N. , Gordon , C. M. , and Laufer , M. R. ( 1998 ). \200\230 Add-back \200 \231 therapy Chapron , C. , Lafay-Pillet , M. C. , Monceau , E. , Borghese , B. , Ng , C. , Souza , C . , et al . ( 2011 ). Questioning patients about their adolescent history can identify mark ers associated with deep infi ltrating endometriosis . Fertil Steril , 95 , 877 \200\22388 1. for endometriosis in adolescents . J Reprod Med , 43 , 164 \200\223172. Maclellan , A. H. , Taylor , A. W. , Wilson , D. H. , and Wilson , D. ( 2000 ). Th e preval ence of pelvic fl oor disorders and their relationship to gender, age, parity and mode of d elivery . BJOG , 1460 \200\2231470. Chung , M. K. , Butrick , C. W. , and Chung , C. W. ( 2010 ). Th e overlap of interstitial cystitis/painful bladder syndrome and overactive bladder . JSLS , 14 , 83 \200\22390. Marjoribanks , J. , Proctor , M. , Farquhar , C. , and Derks , R. S. ( 2010 ). Nonsteroidal anti-infl ammatory drugs for dysmenorrhoea . Cochrane Database Syst Rev , 4 , CD001751 . Clemons , J. L. , Arya , L. A. , and Myers , D. L. ( 2002 ). Diagnosing interstitial cystit is in women with chronic pelvic pain . Obstet Gynecol , 100 , 337 \200\223341. Maroun , P. , Cooper , M. J. , Reid , G. D. , and Keirse , M. J. ( 2009 ). Relevance of gas trointestinal symptoms in endometriosis . Aust N Z J Obstet Gynaecol , 49 , 411 \200\22341 4. Cruccu , G. , Aziz , T. Z. , Garcia-Larrea , L. , Hansson , P. , Jensen , T. S. , Lefaucheu r , J. P. , et al . ( 2007 ). EFNS guidelines on neurostimulation therapy for neuropathic p ain . Eur J Neurol , 14 , 952 \200\223970. Marsh , E. E. , and Laufer , M. R. ( 2005 ). Endometriosis in premenarcheal girls who do no t have an associated obstructive anomaly . Fertil Steril , 83 , 758 \200\223760. Doyle , J. O. , Missmer , S. A. , and Laufer , M. R. ( 2009 ). Th e eff ect of combined sur gical-medical intervention on the progression of endometriosis in an adolescent and young a dult population . J Pediatr Adolesc Gynecol , 22 , 257 \200\223263. Opoku-Anane , J. and Laufer , M. R. ( 2012 ). Prevalence of endometriosis in adolescent gir ls with chronic pelvic pain not responding to conventional therapy . Have we underestimated ? Presented at the North American Society of Pediatric and Adolescent Gynecology , Miami, F L . Dworkin , R. H. , O \200\231Connor , A. B. , Backonja , M. , Farrar , J. T. , Finnerup , N. B. , Jensen , T. S. , et al . ( 2007 ). Pharmacologic management of neuropathic pain: evid ence-based recommendations . Pain , 132 , 237 \200\223251. Parsons , C. L. , and Albo , M. ( 2002 ). Intravesical potassium sensitivity in patients with prostatitis . J Urol , 168 , 1054 \200\2231057. Popat , V. B. , Prodanov , T. , Calis , K. A. , and Nelson , L. M. ( 2008 ). Th e menstrual cycle: a biological marker of general health in adolescents . Ann N Y Acad Sci , 1135 , 43 \200\22351. Economy , K. and Laufer , M. ( 1999 ). Pelvic pain . Adolesc Med , 10 , 291 \200\223304. E vans , S. , Moalem-Taylor , G. , and Tracey , D. J. ( 2007 ). Pain and endometriosis . Pain , 132 Suppl 1 , S22 \200\223225. Proctor , M. L. , Smith , C. A. , Farquhar , C. M. , and Stones , R. W. ( 2002 ). Transcuta neous electrical nerve stimulation and acupuncture for primary dysmenorrhoea . Cochrane Dat abase Syst Rev , 1 , CD002123 . Fauconnier , A. and Chapron , C. ( 2005 ). Endometriosis and pelvic pain: epidemiological e vidence of the relationship and implications . Hum Reprod Update , 11 , 595 \200\223606. Ranney , B. ( 1980 ). Endometriosis: pathogenesis, symptoms, and fi ndings . Giamberardino , M. A. , Berkley , K. J. , Iezzi , S. , De Bigontina , P. , and Vecchiet , L . ( 1997 ). Pain threshold variations in somatic wall tissues as a function of menstrual cy cle, segmental site and tissue depth in non-dysmenorrheic women, dysmenorrheic women and me n . Pain , 71 , 187 \200\223197. Clin Obstet Gynecol , 23 , 865 \200\223874. Schroeder , B. , and Sanfi lippo , J. S. ( 1999 ). Dysmenorrhea and pelvic pain in adolescents . Pediatr Clin North America , 46 , 555 \200\223571. Seaman , H. E. , Ballard , K. D. , Wright , J. T. , and De Vries , C. S. ( 2008 ). Endometr iosis and its coexistence with irritable bowel syndrome and pelvic infl ammatory disease: f i ndings from a national case-control study \200\224Part 2 . BJOG , 115 , 1392 \200\223139 6. Giamberardino , M. A. , Costantini , R. , Aff aitati , G. , Fabrizio , A. , Lapenna , D. , Tafuri , E. , et al . ( 2010 ). Viscero-visceral hyperalgesia: characterization in diff ere nt clinical models . Pain , 151 , 307 \200\223322. Goldstein , D. P. , Decholnoky , C. , Leventhal , J. M. , and Emans , S. J. ( 1979 ). New i nsights into the old problem of chronic pelvic pain . J Pediatr Surg , 14 , 675 \200\22368 0. Simpson , J. L. , Elias , S. , Malinak , L. R. , and Buttram , V. C. ( 1980 ). Heritable as pects of endometriosis. I. Genetic studies . Am J Obstet Gynecol , 137 , 327 \200\223331. Hadfi eld , R. , Mardon , H. , Barlow , D. , and Kennedy , S. ( 1996 ). Delay in the diagno sis of endometriosis: a survey of women from the USA and the UK . Hum Reprod , 11 , 878 \200\223880. Smith , C. A. , Zhu , X. , He , L. , and Song , J. ( 2011 ). Acupuncture for primary dysmenorrhoea . Cochrane Database Syst Rev , 1 , CD007854 . Tokushige , N. , Markham , R. , Russell , P. , and Fraser , I. ( 2006 ). Nerve fi bres in Hoebeke , P. , Van Laecke , E. , Renson , C. , Raes , A. , Dehoorne , J. , Vermeiren , P. , et al . ( 2004 ). Pelvic fl oor spasms in children: an unknown condition responding well t o pelvic fl oor therapy . Eur Urol , 46 , 651 \200\223654. peritoneal endometriosis . Hum Reprod , 21 , 3001 \200\2233007. Tripp , D. A. , Nickel , J. C. , Ross , S. , Mullins , C. , and Stechyson , N. ( 2009 ). Pr evalence, symptom impact and predictors of chronic prostatitis- like symptoms in Canadian m ales aged 16 \200\22319 years . BJU Int , 103 , 1080 \200\2231084. Issa , B. , Onon , T. S. , Agrawal , A. , Shekhar , C. , Morris , J. , Hamdy , S. , et al . ( 2012 ). Visceral hypersensitivity in endometriosis: a new target for treatment? Gut , 61 , 367 \200\223372. SECTION 4 pain in specific populations and diseases 306 Winnard , K. P. , Dmitrieva , N. , and Berkley , K. J. ( 2006 ). Cross-organ interactions b etween reproductive, gastrointestinal, and urinary tracts: modulation by estrous stage and involvement of the hypogastric nerve . Am J Physiol Regul Integr Comp Physiol , 291 , R1592 \200\2231601. Tu , C. H. , Niddam , D. M. , Chao , H. T. , Chen , L. F. , Chen , Y. S. , Wu , Y. T. , et al . ( 2010 ). Brain morphological changes associated with cyclic menstrual pain . Pain , 1 50 , 462 \200\223468. Tu , C. H. , Niddam , D. M. , Chao , H. T. , Liu , R. S. , Hwang , R. J. , Yeh , T. C. , et al . ( 2009 ). Abnormal cerebral metabolism during menstrual pain in primary dysmenorrhea . Neuroimage , 47 , 28 \200\22335. Wright , K. N. , and Laufer , M. R. ( 2010 ). Endometriomas in adolescents . Fertil Steril , 94 , 1529.e7 \200\2239. Vercellini , P. , Fedele , L. , Arcaini , L. , Bianchi , S. , Rognoni , M. T. , and Candian i , G. B. ( 1989 ). Laparoscopy in the diagnosis of chronic pelvic pain in adolescent women . J Reprod Med , 34 , 827 \200\223830. Zhang , G. H. , Dmitrieva , N. , Liu , Y. , McGinty , K. A. , and Berkley , K. J. ( 2008 ). Endometriosis as a neurovascular condition: estrous variations in innervation, vasculariza tion, and growth factor content of ectopic endometrial cysts in the rat . Am J Physiol Regu l Integr Comp Physiol , 294 , R162 \200\223R171. Vincent , K. , Warnaby , C. , Stagg , C. J. , Moore , J. , Kennedy , S. , and Tracey , I. ( 2011 ). Dysmenorrhoea is associated with central changes in otherwise healthy women . Pain , 152 , 1966 \200\2231975. Zondervan , K. T. , Yudkin , P. L. , Vessey , M. P. , Jenkinson , C. P. , Dawes , M. G. , B arlow , D. H. , et al . ( 2001 ). Chronic pelvic pain in the community \200\224 symptoms, i nvestigations, and diagnoses . Am J Obstet Gynecol , 184 , 1149 \200\2231155. Walker , L. S. , Garber , J. , Vanslyke , D. A. , and Greene , J. W. ( 1995 ). Long-term he alth outcomes in patients with recurrent abdominal-pain . J Pediatr Psychol , 20 , 233 \200\223245. Walsh , D. M. , Howe , T. E. , Johnson , M. I. , and Sluka , K. A. ( 2009 ). Transcutaneous electrical nerve stimulation for acute pain . Cochrane Database Syst Rev , 2 , CD006142 . CHAPTER 31 Headaches Andrew D. Hershey Introduction A complaint of headache is one of the most common health com- plaints in child ren and adolescents with migraine representing one of the most common diseases of childhood . However, a complaint of headache is frequently ignored as a problem by patients, parents, teachers, and practitioners. Headaches are either due to an inciting event or illness (sec ondary headache) or can be a disease by itself (primary headache). Secondary headaches are due to an event or ill- ness and can be recognized by their cause and eff ect association w ith this specifi c etiology. Once the inciting event is treated or resolves, the headache s hould also resolve. When the headache persists, addi- tional evaluation is needed. Th is ca use and eff ect relationship can be confusing in patients with a primary headache. Oft enti mes patients with primary headaches make an assumption that their headache is caused by oth er frequent problems in childhood including mild head injury, infections, and allergies. Fu rthermore, some of the sec- ondary causes can exacerbate primary headaches in those patient s prone to headaches. Lack of headache response to treatment of this presumed secondary cau se, or recurrence of the headache without the associated secondary cause, is an indication that the incorrect secondary cause was identifi ed, the incorrect treatment was chosen, or most likely that a primary headache was the actual etiology. and oft en extrapolation from studies in adult headaches are incom- plete or inaccurate whe n translated to children. Future studies should help to fi ll in the current gaps to furthe r improve the lives of these children and their families. Epidemiology Bille reported the fi rst extensive study of pediatric migraine \200\231s epi- demiology in 1962 (Bille, 1962 ). Th is study used its own criteria for the defi nition of migraine in children that are no longer used. Even given that limitation, the study establ ished the basis of pediatric migraine epidemiology recognizing that by age 15 nearly 75% of children will report having a signifi cant headache with migraine in 3.9% of children age 7 to 15 years. Epidemiology studies that have followed confi rmed the high fre- quency of headaches in chi ldren and adolescents with migraines being the more disabling problem (reviewed by Winner a nd Hershey, 2007 ). Th e current standard for diagnosis used in scientifi c studies of head aches is the International Classifi cation of Headache Disorders, second edition (ICHD-II; Headache Classifi cation Subcommittee of the International Headache Society, 2004 ). Th ese criteria have been widely utilized across a variety of countries with some degree of varia tion but consistently demonstrate the high prevalence of migraine during childhood. Epidemiology studies have demonstrated a high frequency of self-reported headache with migr aine occurring typically in one out of ten children. A study from Istanbul, Turkey found 46 .2% of children age 5 to 13 years old (mean 8.2 2.4 years) reported a signifi cant heada che with 3.4% having migraine and an additional 8.7% having probable migraine (Isik et al., 2009 ). Another study from Turkey compared the prevalence of migraine and TTH using ICHD-I I criteria and found migraine to be more common than TTH (21.3% versus 5.1%) with a further increase in the prevalence if the ICHD-II criteria of number of headaches and duration of the headaches were excluded (29.9% and 15.0%, respectively; Unalp et al., 2007 ). All heada che types were found to be more common in females, with an increase in TTH in subjects with a temple location of their pain, having more than one sibling, and parent \200\231s educat ion above high school. School absenteeism was higher in the migraine subjects. Recurrent headaches, especially when episodic, are much more likely to represent primary he adache disorders. Primary head- aches are intrinsic to the nervous system and are the disea se itself. Early recognition of the primary headaches in patients should result in improved response and outcome, minimizing the impact of the primary headaches and disability. Prima ry headaches can be grouped into migraine, tension-type headaches (TTHs), and trigeminal au tonomic cephalalgia, and an additional grouping of rarer headaches without a secondary caus e. Th e primary headache that has the greatest impact on a child \200\231s quality of life and disability is migraine and subsequently is the most frequent primary head- ache brought to the attention of parents, primary care providers, and school nurses ( Figure 31.1 ). Primary headaches Migraine Recurrent pediatric migraine has the most signifi cant impact on a child \200\231s and parents \200\231 lives and consequentially will have the greatest po tential improvement with optimal care. Th ere remain many gaps in the recognition and manag ement of migraine during childhood Epidemiology studies of the transition from late adolescent to young adult years are rare. One relatively older study that focused on 15- to 19-year-olds found up to 28% of this age group had migraine with 19% having only migraine without aura and 9% hav- ing migraine with aura (Split and Neuman, 1999 ). Th ere was an SECTION 4 pain in specific populations and diseases 308 Complaint of Headache Primary Headache Secondary Headache Treat underlying cause Meet ICHD-II Normal Neurological Examination Headaches not exclusively occipital Headaches for more than 6 months Positive Family History Headaches don \200\231t consistently awake O ver age 6 Persists Resolved Re-evaluate Diagnosis and Treatment Acute Treatment Plan If \200\234No \200\235 to any of these consider MRI If more than 1/week: Preventative Treatment Plan Biobehavioral Treatment Plan Figure 31.1 Schematic of diagnosis of evaluation of a child presenting with a complaint of headache. increasing prevalence from age 15 to 19 with a female predomi- nance for all ages. As this appears to be an area of growing preva- lence, additional studies are needed to characteriz e these trends. and SCN1A (Dichgans et al., 2005 ), has provided insight into the importance of channels an d astrocytes in migraine. Several other biological process have been identifi ed to be altered or associated with mig raine in children and adults including immunological changes (Bockowski et al., 2009 ), inc reased levels of calcitonin gene-related peptide in migraine patients (Fan et al., 2009 ), decreased levels of coenzyme Q 10 (Hershey et al., 2007 ), and hormonal changes (Crawford e t al., 2009 ; Kroner-Herwig and Vath, 2009 ; Martin and Behbehani, 2006a , 2006b ). Pathophysiology Th e pathophysiology of migraine in children and adolescents is likely the same as in adults, although the diff erences in headache characteristics in children need t o be further investigated. Th e pathophysiology of migraine can be divided into the underly ing biological risk factors for the expression of migraine and the spe- cifi c biological p rocesses that occur during the attack. Th ere also appears to be neurophysiological changes. In adult patients it has been found t hat interictally, patients with migraine have trigeminal sensitization as revealed by an al tered blink refl ex (De Marinis et al., 2003 ; Katsarava et al., 2002 , 2003; Kaube et al., 2002 ), auditory response (Siniatchkin et al., 2003 ; W. Wang and Schoenen, 1998 ), and se nsitization of the trigeminal vascular sys- tem (Burstein et al., 2005 ). In children, seve ral studies have also identifi ed similar neurophysiological and biological changes includ- ing alterations in the P100 visual response during visual-evoked potential testing (Unay e t al., 2008 ), changes in the somatosensory- evoked potential with treatment of pediatric m igraine (Vollono et al., 2010 ), habituation mismatch negativity and the P300 response (Val eriani et al., 2009 ), and impaired auditory response during an acute migraine using magnet ic encephalography (Korostenskaja et al., 2011 ). In sum, these studies clearly demonstrate that dur- ing an acute migraine, there is brain dysfunction at the cellular and electrical level. Th e predominant risk factor for the development of migraine is the inheritance of the gene tic potential with the environmental infl uences contributing to the phenotypic expression of this geno- type (Hershey, 2007 ; van de Ven et al., 2009; Wessman et al., 2007 ). Severa l models have demonstrated a genetic etiology with shared environmental infl uence and the non-shared environmental infl u- ences. Th e best fi tting model demonstrated a genetic inf l uence of 60% to 70% with a non-shared environmental infl uence compos- ing the remainder. Th is model suggests that migraine is a genetic disease, but with environmental factors si gnifi cantly contributing to its expression. Th e contribution of individual genes has begun to be identifi ed. Th e identifi cation of genes directly responsible for familial hemi- plegic migraine \200\224 CACNA1A (Ophoff et a l., 1996 ; Terwindt et al., 1998 ), ATP1A2 (De Fusco et al., 2003 ; Vanmolkot et al., 2003 ), CHAPTER 31 headaches 309 semistructured interview can assist with assuring the completeness of this evaluation (Hers hey et al., 1999 ). Such an approach has been shown to be very sensitive and specifi c in m aking the appropriate diagnosis of headache (Valentinis et al., 2009 ). Th is evaluation mu st incorporate the children \200\231s responses and not just be completed by the parents, a s parents may be limited in their ability to characterize their children \200\231s headache s. In a study of 3461 parents and children (age 7 to 14 years), parents were accurate in re porting their child \200\231s headache frequency, but were less accurate recognizing other fea- tures associate with migraine (Kroner-Herwig et al., 2009 ). Cutaneous allodynia due to central sensitization has been studied as a clinical marker that refl ects these neurophysiological changes in adults (Ashkenazi et al., 2007 ; Bigal et al ., 2008 ; Burstein and Cutrer, 2000 ; Burstein et al., 2000 ; Jakubowski et al., 2005 ; Mat hew et al., 2004 ). In subjects that have these symptoms during their migraine, there may b e diminished response to treatment (Burstein and Jakubowski, 2004 ; Burstein et al., 2004 ; Jakubowski et al., 2005 ) and possible disease progression. In children this has only begu n to be examined with limited fi ndings (Eidlitz-Markus et al., 2007 ). Diagnosis and evaluation Th e International Headache Society has established diagnostic cri - teria for all headache subtypes including primary and secondary headaches \200\224the ICH D-II (Headache Classifi cation Subcommittee of the International Headache Society, 2004 ). Th ese criteria have been widely used for both the clinical characterization of head- aches and as a foundation for research in headaches. One of the keys to these criteria is the se paration of those headaches thought to be intrinsic to the nervous system (primary headache s) and those headaches directly attributable to another cause (secondary headaches) with th e fi rst step in evaluation of recurrent headaches to eliminate the potential of a secondar y headache. If a secondary etiology is suspected, this should be initially evaluated and tr eated. If the suspected secondary etiology is successfully treated, but the headache persis ts, diagnosis should be re-evaluated. Young children are also limited in their descriptive ability of their headaches and the use of children \200\231s drawings have been dem- onstrated to be both sensitive and specifi c in their diagnosis of pediatric headaches (Stafstrom et al., 2002 , 2005 ; Wojaczynska- St anek et al., 2008 ). In addition, very young children oft en will have additional variants of migraine such as the childhood periodic syndromes. Th e childhood periodic syndromes are thought to be precursors of migraine, are oft en fi rst recognized as a child may not focu s on the head pain, but rather on some of the abdominal symp- toms (cyclic vomiting and abd ominal migraine) or vertigo (benign paroxysmal vertigo of childhood). As the child ages the y are bet- ter able to describe the head pain and the presence of migraine becomes more evi dent. Evaluation guidelines have been developed by the collaboration of the American Academy of N eurology (AAN), Child Neurology Society, and the American Headache Society (Lewis et al., 2 002 ). Th ese guidelines reviewed the existing evidence for the evalua- tion of children wi th headaches and found that the neurological examination is the most critical test for iden tifying potential seri- ous complications, while also confi rming that the occipital locati on warranted further evaluation. When further evaluation is needed, a magnetic resonance im aging (MRI) study is the most sensitive test to identify structural abnormalities and shoul d be the preferred neuroimaging test. Aft er the potential of secondary headache has been eliminated, a diagnosis of a primary he adache can be made. Th e ICHD-II has three main categories of primary headaches and a fourt h category for those rare headaches that are primary, but don \200\231t fall into one of th ese three main categories: migraine, TTHs, and trigeminal auto- nomic cephalalgias (includi ng cluster headaches). In children, the most common types of primary headache are migraine and TTH. Migraine can be subdivided into migraine without aura and migraine with aura, as w ell as additional migraine-related diag- noses including childhood periodic syndromes, reti nal migraine, migraine complications, and probable migraine. In addition to a complete history, general examination, and neu- rological examination, a c omprehensive headache examination should also be performed (Linder, 2005 ). Th e comprehens ive head- ache examination extends the neurological examination to examine for neck tendern ess and stability, the stability of the temporoman- dibular joint, sinus and facial tendern ess including peripheral nerve tenderness, and general cranial palpation. One useful test f or sinus-related symptoms is Muller \200\231s sign in which the patient pres- surizes their sinus and then coughs to create a brief vacuum, thus evaluating the openness of the sinuse s. Th e applicability of this test at the bedside is very useful in dispelling any misperce ptions of the headaches as sinus headaches. Th e ICHD-II criteria for migraine without aura and migraine with aura are undergoing revis ions, but few changes are expected. For a migraine without aura the keys in the diagnosis i nclude a recurrent headache disorder (at least fi ve attacks) lasting 4 to 72 h, character- ized by a focal, throbbing pain, that alters or worsens with activity and is of moderate t o severe in intensity (two of four characteris- tics required) and associated with either n ausea and/or vomiting or with photophobia and phonophobia (Headache Classifi cation Subcomm ittee of the International Headache Society, 2004 ). Th e ICHD-II addressed some of the unique issues related to childhood headaches resulting i n an improvement in the specifi city and sensitivity, although gaps do remain (Hershey et a l., 2005 ; Lima et al., 2005 ; Rossi et al., 2008 ; Ruangsuwan and Sriudomkajorn, 2007 ): t hat childhood migraine tends to be of shorter duration (down to 1 h), that sleep should be included as part of the dura- tion, that the location is more likely bilateral (typically f rontal tem- poral), and that photophobia and phonophobia could be inferred by the parents a nd care providers based on the child \200\231s actions. Th e ICHD-II noted that if the loca tion is exclusively occipital then addi- tional workup is warranted. As part of the history, the impact of the headache on a child \200\231s life needs to be as sessed. Th e impact of a disease can be measured by its eff ect on the quality of life of t he patients as well as the specifi c dis- ability due to a disease. For pediatric migraine several instruments have begun to address these concerns. A review of the literature on the impact of pediatric migraine found 33 studies addressing this question and the tools used found that although the quality was inconsistent, the impact of migraine on a child \200 \231s and family \200\231s lives was signifi cant (Kernick and Campbell, 2009 ). For quality of life one of the most widely administered tools for the assessment of the imp act on pediatrics and adolescents \200\231 quality of life is the PedsQL 4.0 (Varni et al., 2001 ). Th is easily administered instrument address the quality of life in a disease- Although the criteria do not completely recognize all children with migraine, these criteri a should be used as a guideline for making the diagnosis. Use of standardized questionnaire s with a SECTION 4 pain in specific populations and diseases 310 independent manner. Th e quality of life of children with headaches can be measured at a de velopmentally appropriate level and has an impact similar to other chronic disease (Powers et al., 2003 , 2004 ). With treatment this impact improves, although there is preliminary e vidence of a persistent impact even aft er successful treatment. In a multisite study of children with migraine it was found that chil- dren with a body mas s index (BMI) percentile at the extremes (<5th percentile and >95th percentile) and childre n at risk of obesity (85th to 95th percentile) had a higher likelihood of increased frequen cy of headaches and disability. Intervention in the children that were obese or overweight through healthy weight control demonstrated a greater degree of improvement compared to chi ldren whose BMI remained high or increased (Hershey et al., 2009 ). Disease-specifi c loss of function can be persistent in many chronic diseases. Headache and migraine is unique in its episodic nature and may therefore be more variable. For children and ado- lescents PedMIDAS has been developed (Hershey et al., 2001 , 2004 ). Th is tool c an be easily administered in clinical practice and used to assess the disability of an indi vidual patient, the need for preventative medication, and the response to treatment. Sleep disturbances may increase the occurrence of migraine with sleep deprivation or altere d sleep patterns triggering migraines. Furthermore, patients with migraine may also have co morbid sleep disorders. In a study of 1073 adolescents, the most frequent triggering factor for both migraine and non-migraine headaches was \200\230bad sleep \200\231 (Bruni et al. , 2008 ). In a separate study, these sleep disturbances were identifi ed as insuffi cient s leep (65.7%), daytime sleepiness (23.3%), diffi culty falling asleep (40.6), and night waki ng (38%) (Gilman et al., 2007 ). Th e disability and impact of pediatric migraine in tertiary clin- ics is clear and it is b ecoming apparent that this also applies to pae- diatric and adolescent patients in the popu lation. Assessing this can help guide the referral to specialty centers and measure the lon g- term outcome. Psychological factors may play a complicated role in paediat- ric migraine that has been ad dressed in small studies that remain mixed in their fi ndings (Powers et al., 2006 ). In a case \200\223control designed study of 47 children (age 8 \200\22314 years), mothers percei ved emotional and behavioral diffi culties (Vannatta et al., 2008 ), while their classmates identifi ed these same children with higher leader- ship and popularity (Vannattaet al., 2 008 ). Th e impact of psycho- logical factors and school stressors have a signifi cant impa ct on headaches with school phobia and anxiety exacerbating headache frequency (Fujita et a l., 2009 ). Comorbid conditions Th e presence of additional diseases and conditions can complicate the diagnosis, management, and outcome of pediatric migraine. Th e common occurrence of seconda ry conditions that may directly contribute to headaches in children can confuse the underly ing etiology and delay the diagnosis of primary headaches while the impact of these comorbi d conditions may also aff ect the underlying pathophysiological basis of children with migr aine. Several conditions have been demonstrated to have a comorbid relationship with migraine. Th ese include asthma and allergic dis- orders (Gurkan et al., 2000 ; Ku et al., 2006 ), obes ity (Hershey et al., 2009 ; Pinhas-Hamiel et al., 2008 ), epilepsy (Pellock, 2004 ; Piccine lli et al., 2006 ; Stevenson, 2006 ; Yamane et al., 2004 ), sleep disorders (Bruni et al., 1997 ; Gilman et al., Isik et al., 2007 ; 2007 ; Luc et al., 2006 ; Miller et al., 2003 ; P akalnis et al., 2009 ), and psychological/ emotional disorders (Kroner-Herwig et al., 2008 ; Pakalnis et al., 2007 ; Vannatta et al., 2008 ). Th e mechanism by which these comor- bid conditions alter the expression of migraine and thus infl uence the underlying pathophysio logy is largely unknown, but may be a consequence of the diffi culty coping with multiple i llnesses or may have a common pathway in brain pathology. Headache may lead to suicidal ideation. A study of 3963 ado- lescents in Taiwan found that 8.5% had suicidal ideation, with an increased odds ratio of 2.9 for those adolescents with migraine and 4.6 in migraine with aura (S. J. Wang et al., 2009 ). Th is was impacted by bo th headache frequency and disability as measured by PedMIDAS. Treatment Th e treatment of pediatric migraine can be divided into pharma- cological and bi obehavioural medicine. Pharmacological treatments include both acute and preventative strat egies to minimize the impact of the attacks, while biobehavioural treatment includes adhere nce strategies, coping skills, relaxation techniques, and healthy lifestyles. Goals of trea tment should include rapid consistent treatment with a quick return to function (acute trea tment), while also minimizing the frequency and impact of the migraine (preventative and bi obe- havioural treatment). Th ese strategies oft en fail to be employed in general practice . In a study of 151 children age 10.4 3.2 years, only 30.2% were prescribed an appropria te dose of ibuprofen with only 26.5% instructed to treat the headache early (Cuvellier et a l., 2007 ). In addition, lifestyle adjustments were recommended in less than 15% and only 8 % were asked to keep a headache diary. Th us a criti- cal component of pediatric headache m anagement is education of the primary care providers as well as the patients and parents on the incorporation of all of these strategies.