Curr Neurol Neurosci Rep (2015) 15:20 DOI 10.1007/s11910-015-0540-6
HEADACHE (RB HALKER, SECTION EDITOR)
Migraine Management in Children Marcy Yonker & Tara Mangum
# Springer Science+Business Media New York 2015
Abstract Migraine management in children relies on understanding the difference between adult and childhood migraine, being able to identify childhood migraine variants and knowledge of both the pediatric and adult literature regarding treatment. Keywords Migraine . Pediatric . Prophylactic Treatment . Abortive treatment
Introduction Migraine is a common and debilitating disorder in the pediatric population occurring in 5–10 % of the population. Migraine can affect children in multiple arenas of life, through missed school and social activities, and can impair the development of friendships so critical to social development and self-esteem. Treatments that are currently used in the pediatric population are often adapted from studies performed in adults. Abortive management consists primarily of over-the-counter drugs; however, there are several FDA-approved treatments in children. For prophylactic treatment, evidence-based medicine to guide treatment is lacking, so pediatric patients are often prescribed medications used in the adult population based upon side effect profile as well as adherence and response to treatment. Hopefully, ongoing prophylactic trials
This article is part of the Topical Collection on Headache M. Yonker (*) : T. Mangum Department of Neurology, Barrow Neurological Institute at Phoenix Children’s Hospital, 1919 E Thomas Rd, Phoenix, AZ 85016, USA e-mail: [email protected] T. Mangum e-mail: [email protected]
will shed further light on appropriate migraine prophylaxis in this age group. Children also experience variants of migraine not typically seen in adults known as the periodic syndromes. Although these variants often respond to typical migraine treatments, they are diagnoses of exclusion and must be thoroughly evaluated to rule out other more serious neurologic and medical conditions.
Migraine Classification and Treatment There are two major subtypes of migraine identified including migraine without aura and migraine with aura. Migraine Without Aura Typically described as lasting from 4 to 72 hours with unilateral head pain that is described as throbbing. Often, the severity is described as moderate to severe that worsens with exertion. Associated symptoms include nausea with or without vomiting as well as photophobia, phonophobia, and osmophobia. To qualify as migraine without aura under the International Classification of Headache Disorders (ICHD) III criteria [1], a patient must have at least five attacks of these headaches. There is a difference in qualification criteria between the adult and pediatric population. In those under age 18, the h e ad a c h e c a n b e b i l a t e r a l a nd i s p r e d om i n a t el y frontotemporal. In very young children unable to describe their symptomatology, one can infer associated symptoms from the child’s behavior including lying down in a dark room or avoidance behavior due to loud sounds. Migraine duration in children is shorter with a length of 2 hours required to meet ICHD III criteria.
20
Page 2 of 4
Curr Neurol Neurosci Rep (2015) 15:20
Migraine with Aura [2]
Tricyclic antidepressants are often used for migraine prevention in children. For teenagers with difficulty with insomnia, amitriptyline can be helpful in addressing both the lack of sleep that triggers migraine during school and the disorder itself. For those for whom amitriptyline causes difficulty with arising, nortriptyline may be substituted. Generally, in patients with comorbid bipolar disorder, orthostatic hypotension, cardiac arrhythmia, significant constipation, or untreated major depression, these agents should be avoided due to possible exacerbation of these conditions. As with other migraine prophylactic agents, starting with a low initial dose with slow titration in order to avoid side effects is advised. QHS dosing may help to avoid daytime sedation and is generally effective and better tolerated. A starting dose of 10 mg with an ultimate target of 1 mg/kg is recommended by most pediatric headache specialists based on Hershey et al. [4]. Anticonvulsants are frequently prescribed as migraine preventatives. Topiramate has an FDA indication for the treatment of epilepsy and migraine prevention in children and for both prevention of episodic and chronic migraine in adults. As with other migraine preventatives, starting low with slow escalation is recommended to avoid side effects, particularly cognitive ones. Dosing typically ranges from 25 mg/day up to 100 mg bid. For patients who experience cognitive slowing with topiramate but have a reduction in headache frequency, zonisamide may be better tolerated, although the evidence is lacking [7]. Divalproex sodium has an indication for the treatment of epilepsy in children and an indication for the prevention of episodic migraine in adults. In general, this medication is avoided in female patients due to teratogenicity and potential impact on fertility. Hepatotoxicity, thrombocytopenia, increased appetite, and tremor may occur, though it tends to be well tolerated. Open-label trials in children have shown some promise; however, one double-blind, placebo-controlled trial failed to demonstrate superiority over placebo [8–10]. Gabapentin is often used due to safety and tolerability and may help to treat comorbid pain conditions. Recently, comprehensive review of the adult literature shows a lack of evidence for efficacy [11•].
As in adults, children may experience migraine aura, though they may have a more difficult time describing these phenomena. Asking children to draw their headaches may be helpful in identifying the nature of these phenomena. Diagnostic criteria for migraine with aura are otherwise the same as in adults. Treatment of episodic migraine in children has a number of s t ud i e s to s up p or t a n e vi de n ce - b a s e d ap p r o a ch . Acetaminophen, ibuprofen, and sumatriptan nasal have been deemed by the American Academy of Neurology to have adequate evidence to support their use in the pediatric population [3]. Zolmitriptan nasal has adequate double-blind evidence to support its use in teens, though does not have an indication. Almotriptan has an indication in adolescents to treat migraine pain, and rizatriptan has an indication in children age 6 and older. Important factors in determining the choice of abortive treatment in children include age and ability to swallow pills and the presence of significant nausea and vomiting. Generally, pre or co-administration of orally disintegrating ondansetron may be helpful in children who have difficulty keeping down medication, or use of a nasal spray may avoid this issue entirely. For children who are unable to swallow pills, disintegrating preparations such as zolmitriptan or rizatriptan are available. Early identification of the development of migraine for all patients is important in successful treatment, and it is important to take time to educate youngsters on this point. Additionally, documentation for school for migraine medicine to be administered and advocating for students in the school setting so that they are not accused of exhibiting school avoidant behavior is often necessary. For children experiencing four or more migraines per month, prophylaxis is generally instituted to reduce suffering and to improve quality of life. There are two medications with adequate evidence for migraine prevention in children, flunarizine, which is not available in the US, and topiramate, which has an FDA indication. [3]. Current treatments are adapted from studies completed in adults. In general, choice of a prophylactic agent for a specific pediatric patient should involve consideration of comorbidities. Sleeping difficulties, weight, and other health conditions such as comorbid epilepsy, bipolar disorder, and hypertension are taken into account. For younger children, in particular those with insomnia or issues with appetite, cyproheptadine is frequently prescribed, though the evidence to support its use is lacking. Possible side effects of drowsiness dictate that for most patients, at bedtime (QHS) dosing is appropriate, starting at 2 mg and increasing as needed and tolerated. It is a potent appetite stimulant so should be avoided in children who are overweight. Typically, the target dose is anywhere from 2 to 12 mg nightly. Adolescents generally have trouble tolerating the sedating nature of this medication, though it is surprisingly well tolerated in younger children.
Chronic Migraine Chronic migraine occurs in approximately 1 % of the teenage population and approximately 3 % of female teenage migraineurs [12••]. Episodic migraine and chronic migraine are differentiated based on frequency of headaches. Episodic migraines are less than 15 headaches days per month meeting migraine criteria. Chronic migraine is defined as more than 15 headache days per month for greater than 3 months with at least 8 days of headaches composed of migraine features [13]. There is no difference in the criteria for chronic migraine for
Curr Neurol Neurosci Rep (2015) 15:20
children. There are no medications demonstrated as of yet to be effective in treating chronic migraine in children; however, the same strategies are used as in determining desirable agents. Both topiramate and botulinum toxin A have been demonstrated to be efficacious in adults and have FDA indications for treatment of chronic migraine [14]. As with other migraine preventatives in children, there is a lack of class A evidence for the use of botulinum toxin A for prevention of chronic migraine in the pediatric population. Several open-label studies have suggested promise. Most of these studies did not rigorously assure consistency of headache diagnosis [15, 16, 17••], thus conclusions about efficacy in migraine cannot be dawn. One study looked specifically at patients with ICHD II-defined chronic migraine, rather than the non-specific Bchronic daily headache,^ and used a set paradigm [18]. This study showed statistically significant improvement in headache frequency, although it was a retrospective open-label study.
Pediatric Migraine Variants Cyclic vomiting syndrome, benign paroxysmal vertigo, and abdominal migraine are listed by IHS in the criteria as Bchildhood periodic syndromes that are typically precursors to migraine.^ Benign paroxysmal torticollis is listed in the appendix and requires further validation to be considered as a migraine disorder. Cyclic vomiting syndrome consists of recurrent attacks of severe nausea and vomiting that have a duration of anywhere from 1 h to 10 days. The attacks are stereotyped for the individual patient. They consist discrete episodes of high frequency, high-intensity vomiting defined as at least four times per hour. Typically, there is predictable timing for attacks, and the patient is asymptomatic between each attack which must be separated by at least 1 week. Gastrointestinal disorders such as intermittent volvulus, metabolic conditions, and ureteropelvic junction obstruction must be explored as this is a diagnosis of exclusion [19, 20]. A large retrospective study suggested a high rate of abnormal metabolic studies in blood and urine suggestive of a mitochondrial disorder [21•]. Acute treatment may consist of benzodiazepines, antiemetics, or migraine abortives. Careful attention to the medication formulation must be paid as these patients generally cannot keep down oral medications, so nasal, rectal, and injectable preparations may be more effective. These individuals often require IV therapy due to the high frequency, high-intensity vomiting that characterizes this disorder. For patients in whom the attacks occur more than monthly or in whom an effective abortive agent is not found, migraine prophylaxis may be indicated. Appropriate pharmacotherapy in this condition has not been studied in a prospective fashion.
Page 3 of 4 20
Abdominal migraine is also a recurrent disorder. This syndrome is consists of attacks of severe abdominal pain located usually periumbilically, but sometimes more diffuse, described as sore. The pain is typically of moderate to severe intensity. Nausea and vomiting can be seen in abdominal migraine; however, sometimes only symptoms of anorexia or pallor are reported with the abdominal pain. The patient does not typically have a headache. It usually interferes with activities of daily living, impeding school attendance as well as social activities. These episodes last for 2–72 h, and the patient must remain asymptomatic between each episode [22]. Given the non-specific nature of the symptoms, these patients are underdiagnosed and sometimes accused of school avoidant behavior. As in cyclic vomiting, the patient must be screened for any gastrointestinal causes for these symptoms such as intermittent malrotation and appendicitis. Treatment of this disorder is understudied; however, one generally approaches the treatment in the same fashion as one would in a more Bclassic^ migraine disorder [23]. Preventative medications seen in clinical trials to be efficacious were pizotifen, propranolol, and cyproheptadine [24]. Benign paroxysmal vertigo is also episodic in nature. Attacks are very brief in duration, usually lasting seconds to minutes, but occasionally lasting as long as hours. They occur suddenly and resolve spontaneously. Between each attack, the patient is without symptoms and has normal studies including neurologic exam, EEG, and vestibular testing. The vertigo has maximum symptoms upon onset. Parents may observe nystagmus, ataxia, vomiting, as well as fearfulness. Occasionally, the child may have headaches. In younger children, the presence of vertigo may be inferred from behavior, often consisting of the children suddenly grabbing onto a nearby object or family member for support. With these symptoms, the patient should be evaluated for other possible causes. The differential diagnosis includes epilepsy, posterior fossa neoplasm, and vestibular dysfunction so MRI and EEG are generally performed [25]. Treatment is not typically necessary as the attacks are brief. Generally, parental reassurance of the benign nature of this disorder suffices. Benign paroxysmal torticollis is seen primarily in infants and very young children. It usually begins prior to the age of 12 months. These attacks consist of the patient’s head tilting to one side, with slight rotation to the opposite side and may be associated with crying or increased irritability as well as pallor and malaise. These typically remit spontaneously though they may last minutes to days. Again, these patients must have an otherwise normal neurological exam and be asymptomatic between each event [26]. This is also a diagnosis of exclusion. The most common cause of this presentation is congenital muscular torticollis followed by congenital anomalies of occipital condyles and upper cervical spine. Other diagnoses to consider are seizures, Sandifer’s syndrome, neural axis abnormalities, and tumors of the posterior fossa or rarely the upper
20
cervical spine [27]. As discussed above, it awaits further study to be considered as a migraine variant, and appropriate treatment, as of yet, is unknown.
Conclusion Though migraines are as debilitating in the pediatric population as in the adult population, there are key differences that must be acknowledged for appropriate diagnosis in these individuals. Also, recognition of migraine variants remains important. These variants must be approached with caution as these are primarily diagnoses of exclusion, and the patient must be evaluated for other underlying causes. Current treatments are primarily extrapolated from adult data, but there are some studies addressing abortive and prophylactic treatment in children and adolescents. Ongoing studies in this population may shed new light on sound, evidenced-based treatment. Compliance with Ethics Guidelines Conflict of Interest Tara Mangum declares that she has no conflict of interest. Marcy Yonker has received consultancy fees from Amgen and grants from NINDS, Allergan, and Astra-Zeneca. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
References Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1.
Curr Neurol Neurosci Rep (2015) 15:20
Page 4 of 4
Levin M. The international classification of headache disorders, 3rd edition (ICHD III)—changes and challenges. Headache: J Head Face Pain. 2013;53:1383–95. doi:10.1111/head.12189. 2. Cologno D, Torelli P, Manzoni GC. Migraine with aura: a review of 81 patients at 10–20 years’ follow-up. Cephalalgia. 1998;18:690–6. 3. Lewis D, Ashwal S, Hershey A, Hirtz D, Yonker M, Silberstein S. Practice parameter: pharmacological treatment of migraine headache in children and adolescents. Neurology. 2004;63:2215–24. 4. Hershey AD, Powers SW, Bentti AL, et al. Standard dosing of amitriptyline is highly effective in a pediatric headache center population. Headache. 1999;39:357–8. 5. Winner P, Pearlman EM, et al. Topiramate for migraine prevention in children: a randomized, double-blind, placebo-controlled trial. Headache. 2005;45(10):1304–12. 6. Lewis D, Winner P, et al. Randomized, double-blind, placebocontrolled study to evaluate the efficacy and safety of topiramate for migraine prevention in pediatric subjects 12 to 17 years of age. Pediatrics. 2009;123(3):924–34. 7. Bakola E, Skapinakis P, Tzoufi M, Damigos D, Mavreas V. Anticonvulsant drugs for pediatric migraine prevention: an evidence-based review. Eur J Pain. 2009;13(9):893–901.
8.
Caruso JM, Brown WD, et al. The efficacy of divalproex sodium in the prophylactic treatment of children with migraine. Headache. 2000;40(8):672–6. 9. Serdaroglu G, Erhan E, et al. Sodium valproate prophylaxis in childhood migraine. Headache. 2002;42(8):819–22. 10. Apostol G, Cady RK, et al. Divalproex extended-release in adolescent migraine prophylaxis: results of a randomized, double-blind, placebo-controlled study. Headache. 2008;48(7):1012–25. 11.• Mulleners WM, McCrory DC, Linde M. Antiepileptics in migraine prophylaxis: An updated Cochrane review. Cephalalgia. 2014. Evaluated the efficacy of anticonvulsants used in the migraine population and the evidence supporting their use. 12.•• Buse D, Manack A, Fanning K, Serrano D, Reed M, Turkel C, et al. Chronic migraine prevalence, disability, and socioeconomic factors: results from the American Migraine Prevalence and Prevention Study. Headache. 2012;52:1456–70. Demonstrates the difficulties this condition places on each individual patient. Children missing school are also missing social experiences as well as learning opportunies. 13. Diener HC, Dodick DW, Aurora SK, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia. 2010;30(7):804–14. 14. Bigal M, Rapoport A, Sheftell F, et al. The International Classification of Headache Disorders revised criteria for chronic migraine – field testing in a headache specialty clinic. Cephalalgia 2007;230–234. 15. Chan V, Mccabe J, MacGregor D. Botox treatment for migraine and chronic daily headache in adolescents. J Neurosc Nurs. 2009;41(5): 235–43. 16. Ahmed K, Oas K, Mack K, Garza I. Experience with botulinum toxin type A in medically intractable pediatric chronic daily headache. Pediatr Neurol. 2010;43:316–9. 17.•• Bernhard MK, Bertsche A, Syrbe S, Weise S, Merkenschlager A. Botulinum toxin injections for chronic migraine in adolescents—an early therapeutic option in the transition from neuropaediatrics to neurology. Fortschr Neurol Psychiatr. 2014;82(1):39–42. This is a promising treatment for the pediatric population with chronic migraine. It has been approved in adults and is now being also included in the pediatric population. 18. Kabbouche M, O’Brien H, Hershey AD. Onabotulinum toxin A in pediatric chronic daily headache. Curr Neurol Neurosci Rep. 2012;12:114–7. 19. Arruda MA, Guidetti V, Galli F, et al. Primary headaches in childhood—a population-based study. Cephalalgia. 2010;30:1056–64. 20. Fleisher DR. Cyclic vomiting syndrome and migraine. J Pediatr. 1999;134:533–5. 21.• Moses J, Keilman A, Worley S, Radhakrishnan K, Rothner AD, Parikh S. Approach to the diagnosis and treatment of cyclic vomiting syndrome: a large single-center experience with 106 patients. Pediatr Neurol. 2014;50(6):569–73. Improved understanding of timing of onset and details abnormal lab values that suggest related abnormalities that these patients have which may lead to better understanding and therefore improve treatment. 22. Farquar HA. Abdominal migraine in children. BMJ. 1956;i:1082– 5. 23. Russell G et al. Abdominal migraine: evidence for existence and treatment options. Pediatr Drugs. 2002;4:1–8. 24. Drigo P, Carli G, Laverda AM. Benign paroxysmal vertigo of childhood. Brain Dev (Netherlands). 2001;23:38–41. 25. Worawattanakul M et al. Abdominal migraine: prophylactic treatment and follow-up. J Pediatr Gastroenerol Nutr. 1999;28:37–49. 26. Drigo P, Carli G, Laverda AM. Benign paroxysmal torticollis of infancy. Brain Dev. 2000;22:169–72. 27. Herman MJ. Torticollis in infants and children: common and unusual causes. Instr Course Lect. 2006;55:647–53.
HEADACHE (RB HALKER, SECTION EDITOR)
Migraine Management in Children Marcy Yonker & Tara Mangum
# Springer Science+Business Media New York 2015
Abstract Migraine management in children relies on understanding the difference between adult and childhood migraine, being able to identify childhood migraine variants and knowledge of both the pediatric and adult literature regarding treatment. Keywords Migraine . Pediatric . Prophylactic Treatment . Abortive treatment
Introduction Migraine is a common and debilitating disorder in the pediatric population occurring in 5–10 % of the population. Migraine can affect children in multiple arenas of life, through missed school and social activities, and can impair the development of friendships so critical to social development and self-esteem. Treatments that are currently used in the pediatric population are often adapted from studies performed in adults. Abortive management consists primarily of over-the-counter drugs; however, there are several FDA-approved treatments in children. For prophylactic treatment, evidence-based medicine to guide treatment is lacking, so pediatric patients are often prescribed medications used in the adult population based upon side effect profile as well as adherence and response to treatment. Hopefully, ongoing prophylactic trials
This article is part of the Topical Collection on Headache M. Yonker (*) : T. Mangum Department of Neurology, Barrow Neurological Institute at Phoenix Children’s Hospital, 1919 E Thomas Rd, Phoenix, AZ 85016, USA e-mail: [email protected] T. Mangum e-mail: [email protected]
will shed further light on appropriate migraine prophylaxis in this age group. Children also experience variants of migraine not typically seen in adults known as the periodic syndromes. Although these variants often respond to typical migraine treatments, they are diagnoses of exclusion and must be thoroughly evaluated to rule out other more serious neurologic and medical conditions.
Migraine Classification and Treatment There are two major subtypes of migraine identified including migraine without aura and migraine with aura. Migraine Without Aura Typically described as lasting from 4 to 72 hours with unilateral head pain that is described as throbbing. Often, the severity is described as moderate to severe that worsens with exertion. Associated symptoms include nausea with or without vomiting as well as photophobia, phonophobia, and osmophobia. To qualify as migraine without aura under the International Classification of Headache Disorders (ICHD) III criteria [1], a patient must have at least five attacks of these headaches. There is a difference in qualification criteria between the adult and pediatric population. In those under age 18, the h e ad a c h e c a n b e b i l a t e r a l a nd i s p r e d om i n a t el y frontotemporal. In very young children unable to describe their symptomatology, one can infer associated symptoms from the child’s behavior including lying down in a dark room or avoidance behavior due to loud sounds. Migraine duration in children is shorter with a length of 2 hours required to meet ICHD III criteria.
20
Page 2 of 4
Curr Neurol Neurosci Rep (2015) 15:20
Migraine with Aura [2]
Tricyclic antidepressants are often used for migraine prevention in children. For teenagers with difficulty with insomnia, amitriptyline can be helpful in addressing both the lack of sleep that triggers migraine during school and the disorder itself. For those for whom amitriptyline causes difficulty with arising, nortriptyline may be substituted. Generally, in patients with comorbid bipolar disorder, orthostatic hypotension, cardiac arrhythmia, significant constipation, or untreated major depression, these agents should be avoided due to possible exacerbation of these conditions. As with other migraine prophylactic agents, starting with a low initial dose with slow titration in order to avoid side effects is advised. QHS dosing may help to avoid daytime sedation and is generally effective and better tolerated. A starting dose of 10 mg with an ultimate target of 1 mg/kg is recommended by most pediatric headache specialists based on Hershey et al. [4]. Anticonvulsants are frequently prescribed as migraine preventatives. Topiramate has an FDA indication for the treatment of epilepsy and migraine prevention in children and for both prevention of episodic and chronic migraine in adults. As with other migraine preventatives, starting low with slow escalation is recommended to avoid side effects, particularly cognitive ones. Dosing typically ranges from 25 mg/day up to 100 mg bid. For patients who experience cognitive slowing with topiramate but have a reduction in headache frequency, zonisamide may be better tolerated, although the evidence is lacking [7]. Divalproex sodium has an indication for the treatment of epilepsy in children and an indication for the prevention of episodic migraine in adults. In general, this medication is avoided in female patients due to teratogenicity and potential impact on fertility. Hepatotoxicity, thrombocytopenia, increased appetite, and tremor may occur, though it tends to be well tolerated. Open-label trials in children have shown some promise; however, one double-blind, placebo-controlled trial failed to demonstrate superiority over placebo [8–10]. Gabapentin is often used due to safety and tolerability and may help to treat comorbid pain conditions. Recently, comprehensive review of the adult literature shows a lack of evidence for efficacy [11•].
As in adults, children may experience migraine aura, though they may have a more difficult time describing these phenomena. Asking children to draw their headaches may be helpful in identifying the nature of these phenomena. Diagnostic criteria for migraine with aura are otherwise the same as in adults. Treatment of episodic migraine in children has a number of s t ud i e s to s up p or t a n e vi de n ce - b a s e d ap p r o a ch . Acetaminophen, ibuprofen, and sumatriptan nasal have been deemed by the American Academy of Neurology to have adequate evidence to support their use in the pediatric population [3]. Zolmitriptan nasal has adequate double-blind evidence to support its use in teens, though does not have an indication. Almotriptan has an indication in adolescents to treat migraine pain, and rizatriptan has an indication in children age 6 and older. Important factors in determining the choice of abortive treatment in children include age and ability to swallow pills and the presence of significant nausea and vomiting. Generally, pre or co-administration of orally disintegrating ondansetron may be helpful in children who have difficulty keeping down medication, or use of a nasal spray may avoid this issue entirely. For children who are unable to swallow pills, disintegrating preparations such as zolmitriptan or rizatriptan are available. Early identification of the development of migraine for all patients is important in successful treatment, and it is important to take time to educate youngsters on this point. Additionally, documentation for school for migraine medicine to be administered and advocating for students in the school setting so that they are not accused of exhibiting school avoidant behavior is often necessary. For children experiencing four or more migraines per month, prophylaxis is generally instituted to reduce suffering and to improve quality of life. There are two medications with adequate evidence for migraine prevention in children, flunarizine, which is not available in the US, and topiramate, which has an FDA indication. [3]. Current treatments are adapted from studies completed in adults. In general, choice of a prophylactic agent for a specific pediatric patient should involve consideration of comorbidities. Sleeping difficulties, weight, and other health conditions such as comorbid epilepsy, bipolar disorder, and hypertension are taken into account. For younger children, in particular those with insomnia or issues with appetite, cyproheptadine is frequently prescribed, though the evidence to support its use is lacking. Possible side effects of drowsiness dictate that for most patients, at bedtime (QHS) dosing is appropriate, starting at 2 mg and increasing as needed and tolerated. It is a potent appetite stimulant so should be avoided in children who are overweight. Typically, the target dose is anywhere from 2 to 12 mg nightly. Adolescents generally have trouble tolerating the sedating nature of this medication, though it is surprisingly well tolerated in younger children.
Chronic Migraine Chronic migraine occurs in approximately 1 % of the teenage population and approximately 3 % of female teenage migraineurs [12••]. Episodic migraine and chronic migraine are differentiated based on frequency of headaches. Episodic migraines are less than 15 headaches days per month meeting migraine criteria. Chronic migraine is defined as more than 15 headache days per month for greater than 3 months with at least 8 days of headaches composed of migraine features [13]. There is no difference in the criteria for chronic migraine for
Curr Neurol Neurosci Rep (2015) 15:20
children. There are no medications demonstrated as of yet to be effective in treating chronic migraine in children; however, the same strategies are used as in determining desirable agents. Both topiramate and botulinum toxin A have been demonstrated to be efficacious in adults and have FDA indications for treatment of chronic migraine [14]. As with other migraine preventatives in children, there is a lack of class A evidence for the use of botulinum toxin A for prevention of chronic migraine in the pediatric population. Several open-label studies have suggested promise. Most of these studies did not rigorously assure consistency of headache diagnosis [15, 16, 17••], thus conclusions about efficacy in migraine cannot be dawn. One study looked specifically at patients with ICHD II-defined chronic migraine, rather than the non-specific Bchronic daily headache,^ and used a set paradigm [18]. This study showed statistically significant improvement in headache frequency, although it was a retrospective open-label study.
Pediatric Migraine Variants Cyclic vomiting syndrome, benign paroxysmal vertigo, and abdominal migraine are listed by IHS in the criteria as Bchildhood periodic syndromes that are typically precursors to migraine.^ Benign paroxysmal torticollis is listed in the appendix and requires further validation to be considered as a migraine disorder. Cyclic vomiting syndrome consists of recurrent attacks of severe nausea and vomiting that have a duration of anywhere from 1 h to 10 days. The attacks are stereotyped for the individual patient. They consist discrete episodes of high frequency, high-intensity vomiting defined as at least four times per hour. Typically, there is predictable timing for attacks, and the patient is asymptomatic between each attack which must be separated by at least 1 week. Gastrointestinal disorders such as intermittent volvulus, metabolic conditions, and ureteropelvic junction obstruction must be explored as this is a diagnosis of exclusion [19, 20]. A large retrospective study suggested a high rate of abnormal metabolic studies in blood and urine suggestive of a mitochondrial disorder [21•]. Acute treatment may consist of benzodiazepines, antiemetics, or migraine abortives. Careful attention to the medication formulation must be paid as these patients generally cannot keep down oral medications, so nasal, rectal, and injectable preparations may be more effective. These individuals often require IV therapy due to the high frequency, high-intensity vomiting that characterizes this disorder. For patients in whom the attacks occur more than monthly or in whom an effective abortive agent is not found, migraine prophylaxis may be indicated. Appropriate pharmacotherapy in this condition has not been studied in a prospective fashion.
Page 3 of 4 20
Abdominal migraine is also a recurrent disorder. This syndrome is consists of attacks of severe abdominal pain located usually periumbilically, but sometimes more diffuse, described as sore. The pain is typically of moderate to severe intensity. Nausea and vomiting can be seen in abdominal migraine; however, sometimes only symptoms of anorexia or pallor are reported with the abdominal pain. The patient does not typically have a headache. It usually interferes with activities of daily living, impeding school attendance as well as social activities. These episodes last for 2–72 h, and the patient must remain asymptomatic between each episode [22]. Given the non-specific nature of the symptoms, these patients are underdiagnosed and sometimes accused of school avoidant behavior. As in cyclic vomiting, the patient must be screened for any gastrointestinal causes for these symptoms such as intermittent malrotation and appendicitis. Treatment of this disorder is understudied; however, one generally approaches the treatment in the same fashion as one would in a more Bclassic^ migraine disorder [23]. Preventative medications seen in clinical trials to be efficacious were pizotifen, propranolol, and cyproheptadine [24]. Benign paroxysmal vertigo is also episodic in nature. Attacks are very brief in duration, usually lasting seconds to minutes, but occasionally lasting as long as hours. They occur suddenly and resolve spontaneously. Between each attack, the patient is without symptoms and has normal studies including neurologic exam, EEG, and vestibular testing. The vertigo has maximum symptoms upon onset. Parents may observe nystagmus, ataxia, vomiting, as well as fearfulness. Occasionally, the child may have headaches. In younger children, the presence of vertigo may be inferred from behavior, often consisting of the children suddenly grabbing onto a nearby object or family member for support. With these symptoms, the patient should be evaluated for other possible causes. The differential diagnosis includes epilepsy, posterior fossa neoplasm, and vestibular dysfunction so MRI and EEG are generally performed [25]. Treatment is not typically necessary as the attacks are brief. Generally, parental reassurance of the benign nature of this disorder suffices. Benign paroxysmal torticollis is seen primarily in infants and very young children. It usually begins prior to the age of 12 months. These attacks consist of the patient’s head tilting to one side, with slight rotation to the opposite side and may be associated with crying or increased irritability as well as pallor and malaise. These typically remit spontaneously though they may last minutes to days. Again, these patients must have an otherwise normal neurological exam and be asymptomatic between each event [26]. This is also a diagnosis of exclusion. The most common cause of this presentation is congenital muscular torticollis followed by congenital anomalies of occipital condyles and upper cervical spine. Other diagnoses to consider are seizures, Sandifer’s syndrome, neural axis abnormalities, and tumors of the posterior fossa or rarely the upper
20
cervical spine [27]. As discussed above, it awaits further study to be considered as a migraine variant, and appropriate treatment, as of yet, is unknown.
Conclusion Though migraines are as debilitating in the pediatric population as in the adult population, there are key differences that must be acknowledged for appropriate diagnosis in these individuals. Also, recognition of migraine variants remains important. These variants must be approached with caution as these are primarily diagnoses of exclusion, and the patient must be evaluated for other underlying causes. Current treatments are primarily extrapolated from adult data, but there are some studies addressing abortive and prophylactic treatment in children and adolescents. Ongoing studies in this population may shed new light on sound, evidenced-based treatment. Compliance with Ethics Guidelines Conflict of Interest Tara Mangum declares that she has no conflict of interest. Marcy Yonker has received consultancy fees from Amgen and grants from NINDS, Allergan, and Astra-Zeneca. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
References Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1.
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