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. In adults one of the most frequently misdiagnosed headache is sinus headache (Cady and Schr eiber, 2004 ; Schreiber et al., 2004 ). Th e presence of allergy and asthma symptoms in chi ldren may lead to the same confusion. In the screening of a large database of approximately 5000 children presenting to a tertiary headache cen- tre, asthma was reported in 12.0% of these children. In contrast, using the same methodology to screen a tertiary asthma and all ergy clinic, nearly 45.9% of these patients had recurrent headaches (Khurana Hershey et al. , 2005 ). In comparing these two groups the patients referred primarily for a complaint of headache had the highest frequency and disability. Head injury is another frequent event in children and adoles- cents. Many children can reca ll a signifi cant or memorable head injury. When this occurs in a patient with a history of recurrent headache or migraine, it can oft en exacerbate the underlying pri- mary headache disorder and complicate the evaluation and man- agement and may aff ect the overall outcom e. Acute Th e goal of acute treatment of pediatric migraine should be con- sistent response wi th minimal side eff ects and quick return to normal function. A detailed analysis and subse quent guidelines have been reported (Lewis et al., 2004 ). Th e eff ective acute medica- ti ons fall into two broad groups \200\224non-steroidal anti-infl ammatory With the increasing worldwide rate of obesity it has been noted that adults with migraine a nd obesity have a higher frequency and poorer response to treatment. Th is appears to also be present in adolescents. CHAPTER 31 headaches 311 medications (NSAIDs) and triptans. Th e general principle is that NSAIDs (especially ibupro fen) are eff ective when used early in the attacks at an adequate dose (7.5 \200\22310.0 mg /kg/dose) and that triptans are eff ective when the NSAIDs are not completely eff ective, e spe- cially during the more severe attacks. Two triptans are currently approved by the US F ood and Drug Administration (FDA) for children \200\224almotriptan for ages 12 to 17 years and rizatriptan for ages 6 to 17 years. Treatment for children with headache in the emergency depart- ment, however, is oft en lack ing. A Canadian study demonstrated that 44.2% received no treatment (23.3%), simple oral an algesics (with dopamine antagonist prescribed in 20.7%, opiates in 5.5%, ketorolac in 4.7%) and dihydroergotamine (DHE) in 1.0% (Richer et al., 2007 ). One of the most eff ective tre atments for children in the emergency department is the combination of a dopamine antago- n ist (prochlorperazine) with ketorolac (Kabbouche and Linder, 2005 ; Kabbouche et al., 2001 ). One of the reasons for the limited number of positive studies and lack of wider US FDA appr oval of these medications is due to design of the studies that lead to a high placebo respo nse rate ranging from 38% to 53% for pain relief and 17% to 26% for pain freedom at 2 h (Fe rnandes et al., 2008). When compared to adults, however, the overall response of the active medication in pediatric and adolescent studies was similar to the adult studies (Evers et al., 2009 ). When these emergency department treatments are not suc- cessful, inpatient treatment may be necessary. In adults this has classically included the use of DHE and appears to be eff ec tive in children with 74.4% of the patients treated with DHE becoming headache free with a signifi cant improvement in nearly all of the patients (Kabbouche et al., 2009 ). Nausea wa s the most common side eff ect, but otherwise the DHE was well tolerated. In a double-blind, placebo-controlled, three-way crossover study that included children dow n to age 6 (age 6 \200\22317 years old), riza- triptan was found to be consistently more ef f ective than placebo at 2 h \200\22474% for fi rst treatment, 73% for second treatment ver sus 36% for placebo (Ahonen et al., 2006 ). Th is study used a 5 mg dose for children 20 to 39 kg and a 10 mg dose for those greater than 40 kg. Furthermore, rizatriptan was more eff ective at 1 h (50% and 55%) compared with placebo (29%). Medication overuse is oft en a complicating factor in children with frequent headache but c an be avoided with limitations in the number of times an acute medication is used. General guidelines are to limit the use of non-specifi c analgesics to less than two to three times per week, while limiting migraine specifi c agents to less than six times per month. Preve ntative When headaches are frequent (more than once a week) or disabling (PedMIDAS score ab ove 30 \200\224Grade III or IV), preventative treat- ment should be considered. Th e goal o f preventative treatment is to reduce the headache frequency (less than one to two per mont h) with decrease disability (PedMIDAS less than 10) for a sustained period of time (4 to 6 months). Th e presence of comorbid conditions may guide the treatment of choice. No medicat ions are currently approved by the US FDA for the prevention of pediatric headaches and the AAN practice only identifi ed fl unarizine (not available in the US) as having suffi cient evidence (Lewis et al., 2004 ). Using a unique study design \200\224a single-blind, \200\230placebo chal- lenge, \200\231 randomized, double-blind, placebo-controlled, two-way, two-attack crossover, zolmitriptan n asal spray was studied in 248 adolescents (Lewis et al., 2007 ). Of the 171 patients that t reated at least one attack, zolmitriptan nasal spray (5 mg) was found to be superior to pla cebo at 1 h with a 58.1% response for zolmitriptan compared to 43.3% for placebo. Th is stu dy addressed many of the placebo response issue that had complicated previous studies, whil e also using a cross-over design. A randomized, double-blind, placebo-controlled trial of almo- triptan in with 866 adolescen ts (age 12 \200\22317 years) found a 2 h pain-relief rate that was signifi cantly higher fo r all doses of almo- triptan \200\2246.25 mg (71.8%), 12.5 mg (72.9%), and 25 mg (66.7%) co mpared with placebo (55.3%) (Linder et al., 2008 ). Further analy- sis demonstrated superio r sustained response with improvement in migraine-associated symptoms for almotriptan compa red to pla- cebo with the 12.5 mg dose associated with the most favorable response. Agents that have been used for pediatric migraine preven- tion include antidepressant medic ations, including amitriptyline (Hershey et al., 2000 ); antihypertensive medications, incl uding propranolol (Forsythe et al., 1984 ; Ludvigsson, 1974 ; Olness et al., 1987 ); antihi stamine/antiserotonergic medications, including cyproheptadine (Levinstein, 1991 ); and ant iepileptic medica- tions including valproic acid (Apostol et al., 2008 , 2009a , 2009b ; Se rdaroglu et al., 2002 ) and topiramate (Lakshmi et al., 2007 ; Lewis et al., 2009 ; Winner et al., 2005 ). Ault studies have shown that combining NSAIDs with triptans is a highly eff ective way to i mprove the acute treatment of migraine (Brandes et al., 2007 ; Smith et al., 2005 ). Additionally, neutriceuticals may also be eff ective in treating pediatric headaches. Coenz yme Q 10 appears to be defi cient in a signifi cant number of children and adolescents with frequent head- aches (Hershey et al., 2007 ; Slater et al., 2011 ). Supplementation was no ted to be associated with improvement in headache fre- quency in this open-labeled clinic o bservation study. Other agents that are also considered include butterbur \200\22477% of ch ildren having a 50% or greater reduction in headache frequency in an open-label study (Poth mann and Danesch, 2005 ), ribofl avin (Bruijn et al., 2010 ; O \200\231Brien and Hershey, 2 010 ), and magnesium (F. Wang et al., 2003 ). When acute treatment fails to relieve the headache, patients fre- quently visit the emergen cy department (Walker, 2008 ). A study of 432 children (2 \200\22318 years old, mean 8.9 ye ars) visiting a paedi- atric emergency department found that headache was responsible for 0 .8% of all the visits with respiratory disorders contributing 19.2% to the etiology, migrai nes 18.5%, TTH 4.6%, post-traumatic headaches 5.5%, meningitis 4.1%, hydrocephalus 0.9%, an d brain tumors 0.7% (Conicella et al., 2008 ). A study of 550 patients over a 12-month peri od, found headache to be responsible for 1.0% of the visits with primary headache represent ing 56.7% (9.6% migraine) and 42% as secondary headaches (Scagni and Pagliero, 2008 ). Vira l illness contributed to 90.5% of the secondary headaches with a seri- ous illness found in 4%. Only 40.5% of the patients received phar- macological treatment. Biobehavioural Biobehavioural therapy, or the incorporation of adherence, educa- tion, life style adjustment, and coping skills, is also essential to the management of pediatric migra ine (Powers and Andrasik, 2005 ). Educating the patient and family on the proper use of the ir acute and SECTION 4 pain in specific populations and diseases 312 preventative medication with a discussion about the importance of treatment and inclusion o f the child in the decision-making proc- ess may greatly improve the adherence to the treat ment approach. Adherence assessment has not yet been well studied in pediatric migraine, bu t is being recognized as an important component of the management of children with chronic or episodic disorders. headaches and can serve to guide the interview process. Children \200\231s headache diagnos is is further complicated by the shorter duration of the headaches with spontaneous resolut ion, or response to rest, sleep, or behavioral therapies. Due to these issues, it may be ne ces- sary to observe the child over time and utilize diaries to identify the diagnostic cha racteristics. Incorporation of healthy lifestyle habits is also important to eff ec- tive headache manage ment. Th is includes adequate hydration with limited use of caff eine-containing beverages; a healthy, balanced diet while avoiding skipping meals; regular exercise; and suffi cient sleep on a regular basis. As already discussed, sleep disturbances have begun to be studied as a signifi cant contributor to pediatric migraine and treatment of the disturbances need s to be included in the treatment plan. Th e typical features that separate TTH from migraine are a lack of throbbing or pulsatile quality of the pain, a diff use location, a mild severity, and lack of signifi cant associa ted symptoms. Some researchers have argued that TTH and migraine are in a continuum (Cady e t al., 2002 ), while others have argued that these are sepa- rate diseases with a broad spe ctrum of headaches represented by migraine (Lipton et al., 2000 ). Until biomarkers are ava ilable, this debate and the diagnosis of these two primary disorders will con- tinue to hav e an overlapping diffi culty. In order to attain this treatment several diff erent approaches have recently been reported . Using telephone-assisted behavioral therapy, there was a trend to improvement in 34 adole scents aft er a 3- and 8-month period (Cottrell et al., 2007 ). Another study has begun to address the feasibility of using a CD-ROM to teach this behavioral therapy (Connelly et al. , 2006 ). Epidemiology In adults, TTHs are thought to be the most common type of pri- mary headache d isorder, with a lifetime prevalence ranging from 30% to 78%. Yet TTHs remain the least well studied of the primary headache disorders. Th is is likely due to their low severity and l ack of impact on a patient \200\231s quality of life and disability. Tension-type headaches TTHS are generally thought of as mild recurrent headaches. Other nam es for this type of headache have included muscle contraction headache, idiopathic headache , and tension headache. Th ey can be infrequent (less than one a month), frequent (more tha n once a month, but not more than half the month), and chronic (more than half the month). Th e headache severity is usually described as mild to moderate with the location being dif f use or in a band-like pat- tern and have a pressing pain quality. Similar to migraine, TT H is a primary headache disorder, and secondary aetiologies should be identifi ed and the p atient should have a normal neurological exam- ination and comprehensive headache examinati on. As a primary headache, the most diffi cult component of making the diagnosis of TTH is separating it from migraine. Th is is largely due to the over- lapping diagnostic character istics, especially in severity (TTH as mild to moderate, migraine as moderate to severe) an d associated symptoms (the allowance of nausea, photophobia, or phonophobia in TTH, but not vomiting). In children, all headache disorders have been less well studied and this is especially true for TTH (reviewed by Anttila, 2006 ). Epidemiology rates of TTH in children have been vari able and have ranged from 0.9% (Abu-Arafeh and Russell, 1994 ) to 73% (Barea et al., 1996 ) , with the most frequent range reported as 10% to 25% (Anttila, 2006 ). Using ICHD-I criter ia, TTH are reported in 9.8% of 7- to 16-year-olds in Sweden (Laurell et al., 2004 ) and 12 % of 12-year-olds in Finland (Anttila et al., 2002a ). In the study from Finland, many of t he children diagnosed with TTH had migrain- ous features with lack of muscle tenderness in children with TTH (Anttila et al., 2002 ). Both of these studies demonstrated an increas- i ng frequency of TTH in girls over boys during adolescence. As this is also seen in migraine , there remains the possibility of an over- lapping evolution of the diagnosis from migrain e to TTH and vise versa. Th e epidemiological identifi cation of TTH, however, is hampered by the lack of attention paid to these headache disorders, especially when infrequent. Th erefore, population-based epidemiology stud- ies may underestimate the prevalence of TTH due to a recall bias, while the inaccuracies of the recall of individual features may over- estimate the misclassifi ed TTH that should actually be considered migraine. Regardless of these limitations, both mig raine and TTH are common pain problems for both children and adults. Th e ICHD-II (Headache Classifi cation Subcommittee of the International Headache Society, 2004 ) identifi es four subtypes of TTH: ICHD 2.1 infrequent episodic tension-type headache , ICHD 2.2 frequent episodic tension-type headache, ICHD 2.3 chronic tension-type headache, and ICHD 2.4 probable tension-type head- ache. Th ese are further subclassifi ed according to the presence or absence of pericranial tenderness. Treatment Once it has been determined that a patient has TTH, a manage- ment plan needs to be developed. As is the case for most head- ache treatment studies in children, no large-sc ale treatment studies have been performed with a focus on TTH in children. For adults, seve ral large studies that meet standard study guidelines have been performed (reviewed by Fuma l and Schoenen, 2008 ) and the same basic principles of migraine management can be applied to TTH management \200\224acute therapy, preventative therapy, and biobehav- ioural therapy with psychological intervention. Diagnosis Establishing a diagnosis of TTH in children is oft en diffi cult due to a lack of recognition of the headache characteristics, either due to a misunderstanding of the quest ions asked by the interviewer or separating the features from migraine. Th is may be height ened in TTH due to the lack of disease impact and disability, such that the patient and par ent may not attend to these features as readily as they do for migraine. As TTHs are oft en mild, the patient and parent may be vague in their descriptions with the parents unaware of the frequency of the headaches, especially if mild. Using standardized criteria such as the ICHD-II criteria, is useful in the diagnosis of pediatric Acute Episodic TTH may be self-limited and may be managed with sim- ple analgesics such as acetaminophen and NSAIDs \200\224ibuprofen or CHAPTER 31 headaches 313 naproxen sodium. Both of these groups of medicines have been demonstrated to be eff ective in migraine in children and, by impli- cation, may also be useful in TTH in children. mind that patients with known medical problems are not protected from primary headaches and if there is not a direct cause and eff ect and variation with treatment, a diagnosis and m anagement of a pri- mary headache disorder should be considered. In addition, as TTH may be mild, but become frequent, the patient and family should be caut ioned about the overuse of acute medication and subsequent medication overuse. Th is may be a major contributor to chronic daily headache. Since a mild TTH with no disability is oft en treated at home without or with limited medical professional intervention, this needs to be addressed at the initial use of acute medication. Vascular disorders Vascular disorders can frequently have a headache as one of their sympto ms (Roach and Riela, 1995 ). Th is can be attributed to ischaemia, hemorrhage, or diseases of the blood vessels includ- ing malformations, arteritis, injury to the vessels (i.e. diss ection or surgical intervention), thrombosis, or genetic diseases of the blood vessels (i.e . CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoence phalopathy), mitochon- drial encephalomyopathy, lactic acidosis, and stroke-like episodes ( MELAS)). Th ese disorders for the most part are rare in children, but should be considered when other symptoms are present. When these simple analgesics are ineff ective, the diagnosis should be re-evaluated and a c onsideration of migraine or other primary headache treatment initiated. Th is can include t he triptans or indomethacin and may unmask an indomethacin responsive primary headache. Preventative When the TTH become frequent, preventative therapies may become necessary, esp ecially if disability occurs. Th is is oft en the trigger for parents to seek medical atten tion for their child. For adults, amitriptyline has been demonstrated to be useful for prop h- ylaxis of chronic TTH (Bedsten et al., 1996 ; Gobel et al., 1994 ). Th e preventative tr eatment of TTH in children is lacking and oft en gets overlapped with the treatment of chro nic migraine or chronic daily headache. In adults with chronic TTH, the combination of amit riptyline and cognitive therapy may be even more eff ective than either one by itself. Cerebrovascular disease in children is rare occurring at a rate of 2.5/100 000. Symptoms of acute neurological changes occur at the same time of the headache. Th is needs to be consi dered on the fi rst presentation of hemiplegic migraine, even in the setting of a family hi story. Hemorrhage may be secondary to rupture of a vascular mal- formation or aneurysm or secondar y to trauma. Th e presenting symptom is most oft en an acute severe headache ( \200\230wors t headache of my life \200\231) associated with loss of consciousness, meningismus and loca l neurological symptoms. An underlying neurocutaneous dis- order should be sought. If this diagnosis is suspected, imaging will usually show the hemorrhage. Angiography or venography may delineate the specifi c etiology. Biobehavioural Biobehavioural therapy includes adherence therapy, lifestyle adjustments, an d specifi c psychological interventions including biofeedback-assisted relaxation therapy ( BART) (Bussone et al., 1998 ) and cognitive-behavioral therapy. In a school-based study for the treatment of childhood headaches including TTH, adoles- cents responded well to relaxa tion therapies (Larsson et al., 2005 ). In children with TTH, biobehavioural therapy has be en demon- strated to have prolonged eff ects over 3 years (Grazzi et al., 2001 ) and may be comparable to amitriptyline (Grazzi et al., 2004 ). Vasculitis is being reported with increased frequency in children and adolescents but remai ns uncommon. Headaches occur in 40% to 70% of patients with primary central nervous system (CNS) vas- culitis. It may occur in the setting of an autoimmune disorder such as systemic lupus erythematosus, polyarteritis, Wegener \200\231s granulo- matosis, and Sj gren \200 \231s syndrome. Although headaches may uncom- monly be the initial symptom, other systemic symptoms have usually preceded the headache. Th e headaches may resemble either chronic TTH or migraine and usually exacerbate when the under- lying autoimmune disorder worsens. Othe r neurological symptoms may include behavioral changes, cognitive dysfunction, seizures, an d focal defi cits. An MRI and magnetic resonance angiogram may show abnormalities. Cerebros pinal fl uid (CSF) may be abnormal. Angiography may be required. Overall, the treatment plan needs to incorporate all three com- ponents to be successful. W ith time, the TTH may also evolve into migraine or other primary headaches disorders and th e treatment plan further adjusted (Kienbacher et al., 2006 ). Secondary headaches Secondary headaches are frequently diagnosed in children. Oft entimes t his is a misdiagnosis of a primary headache, but needs to be ruled out and treated when sus pected. A thorough review of secondary headaches can be found in Th e Headaches (3rd editio n; Olesen et al., 2006 ) or Wolff \200\231s Headaches and Other Head Pain (8th edition; Si lberstein et al., 2008 ). Th e remainder of this chapter will highlight a few secondary hea daches that can be seen in children. Emboli and thrombosis may be idiopathic or secondary trauma, coagulation disorders, autoimm une disorders, and congenital heart disease. Conditions such as moyamoya disease, fi bromus cular dys- plasia, arterial dissection, tumor, trauma, sickle cell anemia, hemophilia, and dehydration may also cause secondary vascular disease. Venous sinus thrombosis may occur in the presence of an under- lying metabolic or systemic infection, a coagulation disorder, or patients who are dehydrated. Th e patients may presen t with head- ache, altered consciousness, lethargy, focal neurological symptoms and seizure s. Th e neurological examination is usually abnormal and the MRI, as well as the magnetic r esonance venogram, may show the thrombosed vessel and/or hemorrhage secondary to venous thr ombosis. Consideration should be given to this diagno- sis in the presence of a coagulopath y, systemic malignancy, and/or chemotherapy. Medical-systemic causes of headache Secondary headaches can occur as a symptom of other med ical problems or to primary neurological disorders. Th is can include infections, metabolic disorders, renal problems, mitochondrial disorders, increased blood pressure, and hematolo gical disorders. When a patient has a known medical condition either the condition itself o r the treatment may induce headaches. It must be kept in SECTION 4 pain in specific populations and diseases 314 Neoplasms Intracranial tumors are the second most common type of neo- plasm in children (Ho nig, 1982 ). In children younger than 15 years, the incidence is 2.4/100 000. Certain genet ic syndromes such as neurofi bromatosis, tuberous sclerosis, von Hippel \200\223Lindau dise ase, and ataxia telangiectasis pose a greater risk for the development of neoplasms. to the development of frequent headaches, they should be limited for 4 to 6 weeks. At that point they can be re-introduced, but at a limited frequency. Infectious disorders Systemic infectious disorders or those localized to the CNS are com- m only associated with headache. Th e presence of an elevated tem- perature and tachycardia a lone frequently give rise to a pounding headache which is oft en relieved when the temperat ure is lowered and the infection is treated. Among the common infections seen are sinusitis , otitis media, and pharyngitis. Among the infections aff ect- ing the CNS are meningitis, aseptic meningitis, and encephalitis (Bale, 1999 ). Brain abscess is uncommon. It occurs mo re commonly in children with cyanotic congenital heart disease, open head trauma, chronic e ar infections, chronic pulmonary disease, post-neurosurgical procedures, and in the immunoc ompromised patient. Th e fear of a brain tumor is one of the major concerns of parents bringing their children to the physician for evaluation of headache. However, the prevalence of primary headaches f ar outweighs the frequency of tumor-related headaches. Th ere is a clear association betwee n brain tumors and headaches with the majority of brain tumor having headache as one of the presenting manifestations. Th e headache due to a brain tumor is the result of increased intracranial pressure due to the mass eff ect of the tumor or a block- age of cerebral spinal fl uid drainage. In additi on, the eff ects of the brain tumor on the surrounding tissue also induce changes in the ne urological examination or neurological symptoms (Lewis et al., 2002 ). Other symptoms of br ain tumor include seizures, ataxia, weakness, visual abnormalities, lethargy, and personali ty change in the majority of such patients \200\224the course will be progressive. Th e neu rological examination will be abnormal and the diagnosis can be confi rmed by neuroimaging. In any CNS infection, in addition to symptoms of increased intracranial pressure or progres sive neurological disease, mening- ismus, rash, or elevated temperature may be present. Ini tial evalu- ation should include a brain imaging procedure to rule out a mass lesion. If at all possible, this should be performed prior to any lum- bar puncture. Conclusion Th e majority of recurrent headaches in children and adolescents are primary hea daches. Secondary headaches, however, occur due to systemic or CNS disease. Th e history an d physical examination should help identify whether a headache is primary or secondary with appropriate laboratory tests and neuroimaging confi rming the suspicion. Ultimately, the d iagnosis of the secondary headache will be the resolution of the headache once the secondar y cause has been eff ectively treated, while persistence of recurrent headaches without the secondary cause helps confi rm the diagnosis and man- agement of primary headaches. Due to the continued growth of the tumor, the headache pat- tern is usually chronic, progre ssive, with increases in frequency and severity over time. Th e rapidity of the growth of t he tumor and the adaptability of the intracranial space to respond to this growth can modif y the timing of the headache \200\231s presentation. It is frequently reported to occur in the morning due to a \200\230ball-valve \200\231 eff ect in which the CSF pressure builds in the recumbent position and is relieved by posture \200\224the opposite of idiopathic int racranial hypertension. Substance-induced headache Prescribed medications, illicit drugs, dietary compounds, and to x- ins can cause headaches (Silberstein et al., 1998 ). Th ese substances may initiate a he adache, exacerbate a pre-existing headache, or cause headache on its withdrawal. A through history of exposure to medications and non-medications needs to be performed and removal or alteration of these substances, if possible, may be neces- sary before the headache respon ds. Stimulants used in the treat- ment of attention-defi cit disorder may initiate headache , especially if they are restarted at maximum dosage aft er not having been taken for sever al days to weeks. One common stimulant used in children and adults is caff eine and caff ei ne addiction and its withdrawal can contribute to headache and exacerbate primary headaches . References Abu-Arafeh , I. and Russell , G. ( 1994 ). Prevalence of headache and migraine in schoolchildren . Br Med J , 309 , 765 \200\223769. Ahonen , K. , Hamalainen , M. L. , Eerola , M. , and Hoppu , K. ( 2006 ). A randomized tria l of rizatriptan in migraine attacks in children . Neurology , 67 (7), 1135 \200\2231140. Anttila , P. ( 2006 ). Tension-type headache in childhood and adolescence . Lancet Neurol , 5 (3), 268 \200\223274. Anttila , P. , Metsahonkala , L. , Aromaa , M. , Sourander , A. , Salminen , J. , Helenius , H. , et al . ( 2002 a). Determinants of tension-type headache in children . Cephalalgia , 22 (5), 401 \200\223408. Anttila , P. , Metsahonkala , L. , Mikkelsson , M. , Aromaa , M. , Kautiainen , H. , Salmin en , J. , et al . ( 2002 b). Muscle tenderness in pericranial and neck-shoulder region in c hildren with headache. A controlled study . Cephalalgia . 22 (5), 340 \200\223344. Medication overuse headache (MOH) can occur with overuse of over-the-counter analgesic medi cation or prescription medica- tions. Th is has formerly been referred to as analgesic rebo und head- ache. It is oft en associated with a gradual increase in frequency of medications that were successful or partially successful in headache treatment. Th ese medications are typically taken at low doses or with repeated doses building to very frequent usage \200 \224up to daily. ICHD-II defi nes medication overuse as using prescription medica- tions mo re than ten times per month or over-the-counter analgesics more than 15 times per month, in creasing the likelihood of MOH. Almost all medications used for the acute treatment of migr aine can potentially cause MOH. If MOH is thought to be a contributor Apostol , G. , Cady , R. K. , Laforet , G. A. , Robieson , W. Z. , Olson , E. , Abi-Saab , W. M. , et al . ( 2008 ). Divalproex extended-release in adolescent migraine prophylaxis: r esults of a randomized, double-blind, placebo-controlled study . Headache , 48 (7), 1012 \200\2231025. Apostol , G. , Lewis , D. W. , Laforet , G. A. , Robieson , W. Z. , Fugate , J. M. , Abi- S aab , W. 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Bedsten , L. , Jensen , R. , and Olesen , J. ( 1996 ). A non-selective (amitriptyline), but not a selective (citalopram), serotonin reuptake inhibitor is eff ective in the prophylact ic treatment of chronic tension-type headache . J Neurol Neurosurg Psychiatry , 61 , 285 \200\223290. De Marinis , M. , Pujia , A. , Natale , L. , D \200\231Arcangelo , E. , and Accornero , N. ( 2003 ). Decreased habituation of the R2 component of the blink refl ex in migraine patien ts . Clin Neurophysiol , 114 (5), 889 \200\223893.