Pathophysiology, clinical features, and diagnosis of migraine in children
- Amy Gelfand, MD
Amy Gelfand, MD
- Assistant Professor of Neurology and Pediatrics
- Director of Pediatric Headache
- University of California, San Francisco (UCSF)
- Section Editors
- Marc C Patterson, MD, FRACP
Marc C Patterson, MD, FRACP
- Section Editor — Pediatric Neurology
- Professor of Neurology, Pediatrics, and Medical Genetics
- Chair, Division of Child and Adolescent Neurology
- Mayo Clinic College of Medicine
- Jerry W Swanson, MD, MHPE
Jerry W Swanson, MD, MHPE
- Section Editor — Headache
- Professor of Neurology
- Mayo Clinic College of Medicine
Migraine is the most common disabling primary headache disorder that occurs in children and adolescents. It is characterized by headache that is often throbbing in character and accompanied by symptoms such as photophobia, phonophobia, nausea, vomiting, and movement sensitivity.
The epidemiology, pathophysiology, clinical features, and diagnosis of migraine headaches in children are reviewed here. Classification and treatment of migraine headaches in children and an approach to the general evaluation of headaches in children are discussed separately. (See "Classification of migraine in children" and "Acute treatment of migraine in children" and "Headache in children: Approach to evaluation and general management strategies".)
The classification of migraine in children is discussed in detail separately. (See "Classification of migraine in children".)
Migraine is thought to have a polygenetic and multifactorial etiology . Despite the strong genetic underpinnings of migraine, the specific genes underlying migraine have not been fully delineated, with the exception of the rare subform of familial hemiplegic migraine. (See "Hemiplegic migraine", section on 'Familial hemiplegic migraine'.)
No single theory or hypothesis has yet explained all of the phenomena that occur with migraine. The once popular vascular theory of migraine, which suggested that the headaches were caused by the dilatation of blood vessels while the aura resulted from vasoconstriction, has been discredited. In spontaneous migraine attacks imaged with magnetic resonance angiography, there is no extracranial artery dilation and only minimal intracranial artery dilation . Successful treatment of the attacks with sumatriptan did not cause intracranial vasoconstriction. The throbbing nature of migraine head pain does not represent perception of one's own arterial pulse, as the throbbing percept rhythm and the arterial pulse rhythm are distinct from, and out of phase with, one another . A central oscillation in nociceptive processing may underlie the throbbing percept of migraine head pain.
- Ducros A, Tournier-Lasserve E, Bousser MG. The genetics of migraine. Lancet Neurol 2002; 1:285.
- Amin FM, Asghar MS, Hougaard A, et al. Magnetic resonance angiography of intracranial and extracranial arteries in patients with spontaneous migraine without aura: a cross-sectional study. Lancet Neurol 2013; 12:454.
- Ahn AH. On the temporal relationship between throbbing migraine pain and arterial pulse. Headache 2010; 50:1507.
- Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 2013; 33:629.
- Welch KM, Barkley GL, Tepley N, Ramadan NM. Central neurogenic mechanisms of migraine. Neurology 1993; 43:S21.
- Weiller C, May A, Limmroth V, et al. Brain stem activation in spontaneous human migraine attacks. Nat Med 1995; 1:658.
- Gervil M, Ulrich V, Kaprio J, et al. The relative role of genetic and environmental factors in migraine without aura. Neurology 1999; 53:995.
- Bolay H, Reuter U, Dunn AK, et al. Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med 2002; 8:136.
- Kaube H, Katsarava Z, Przywara S, et al. Acute migraine headache: possible sensitization of neurons in the spinal trigeminal nucleus? Neurology 2002; 58:1234.
- Leão AA. Pial circulation and spreading depression of activity in cerebral cortex. J Neurophysiol 1944; 7:391.
- Gursoy-Ozdemir Y, Qiu J, Matsuoka N, et al. Cortical spreading depression activates and upregulates MMP-9. J Clin Invest 2004; 113:1447.
- Martignoni E, Solomon S. The complex chronic headache, mixed headache, and drug overuse. In: The Headaches, Olesen J, Tfelt-Hansen P, Welch KM (Eds), Raven, New York 1993. p.849.
- Winner P, Ricalde O, Le Force B, et al. A double-blind study of subcutaneous dihydroergotamine vs subcutaneous sumatriptan in the treatment of acute migraine. Arch Neurol 1996; 53:180.
- Chugani DC, Niimura K, Chaturvedi S, et al. Increased brain serotonin synthesis in migraine. Neurology 1999; 53:1473.
- Garza I, Swanson JW. Prophylaxis of migraine. Neuropsychiatr Dis Treat 2006; 2:281.
- Hamel E. The biology of serotonin receptors: focus on migraine pathophysiology and treatment. Can J Neurol Sci 1999; 26 Suppl 3:S2.
- Rosenfeld MG, Mermod JJ, Amara SG, et al. Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing. Nature 1983; 304:129.
- Skofitsch G, Jacobowitz DM. Calcitonin gene-related peptide coexists with substance P in capsaicin sensitive neurons and sensory ganglia of the rat. Peptides 1985; 6:747.
- Jansen-Olesen I, Mortensen A, Edvinsson L. Calcitonin gene-related peptide is released from capsaicin-sensitive nerve fibres and induces vasodilatation of human cerebral arteries concomitant with activation of adenylyl cyclase. Cephalalgia 1996; 16:310.
- Goadsby PJ, Edvinsson L, Ekman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol 1990; 28:183.
- Goadsby PJ, Edvinsson L. The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann Neurol 1993; 33:48.
- Lassen LH, Haderslev PA, Jacobsen VB, et al. CGRP may play a causative role in migraine. Cephalalgia 2002; 22:54.
- Fan PC, Kuo PH, Chang SH, et al. Plasma calcitonin gene-related peptide in diagnosing and predicting paediatric migraine. Cephalalgia 2009; 29:883.
- Silberstein SD, Edvinsson L. Is CGRP a marker for chronic migraine? Neurology 2013; 81:1184.
- Cady RK, Vause CV, Ho TW, et al. Elevated saliva calcitonin gene-related peptide levels during acute migraine predict therapeutic response to rizatriptan. Headache 2009; 49:1258.
- Dodick DW, Goadsby PJ, Silberstein SD, et al. Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: a randomised, double-blind, placebo-controlled, exploratory phase 2 trial. Lancet Neurol 2014; 13:1100.
- Dodick DW, Goadsby PJ, Spierings EL, et al. Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Neurol 2014; 13:885.
- Lamy C, Giannesini C, Zuber M, et al. Clinical and imaging findings in cryptogenic stroke patients with and without patent foramen ovale: the PFO-ASA Study. Atrial Septal Aneurysm. Stroke 2002; 33:706.
- Anzola GP, Magoni M, Guindani M, et al. Potential source of cerebral embolism in migraine with aura: a transcranial Doppler study. Neurology 1999; 52:1622.
- Del Sette M, Angeli S, Leandri M, et al. Migraine with aura and right-to-left shunt on transcranial Doppler: a case-control study. Cerebrovasc Dis 1998; 8:327.
- Sarısoy S, Aydın ÖF, Sungur M, et al. The relationship between migraine and right-to-left shunt in children. Eur J Pediatr 2011; 170:365.
- McCandless RT, Arrington CB, Nielsen DC, et al. Patent foramen ovale in children with migraine headaches. J Pediatr 2011; 159:243.
- Mortimer MJ, Kay J, Jaron A. Epidemiology of headache and childhood migraine in an urban general practice using Ad Hoc, Vahlquist and IHS criteria. Dev Med Child Neurol 1992; 34:1095.
- Elser JM, Woody RC. Migraine headache in the infant and young child. Headache 1990; 30:366.
- Victor TW, Hu X, Campbell JC, et al. Migraine prevalence by age and sex in the United States: a life-span study. Cephalalgia 2010; 30:1065.
- Congdon PJ, Forsythe WI. Migraine in childhood: a study of 300 children. Dev Med Child Neurol 1979; 21:209.
- Lee LH, Olness KN. Clinical and demographic characteristics of migraine in urban children. Headache 1997; 37:269.
- Arruda MA, Bigal ME. Migraine and migraine subtypes in preadolescent children: association with school performance. Neurology 2012; 79:1881.
- Lipton RB, Manack A, Ricci JA, et al. Prevalence and burden of chronic migraine in adolescents: results of the chronic daily headache in adolescents study (C-dAS). Headache 2011; 51:693.
- Charles A. The evolution of a migraine attack - a review of recent evidence. Headache 2013; 53:413.
- Dooley JM, Pearlman EM. The clinical spectrum of migraine in children. Pediatr Ann 2010; 39:408.
- Kelman L. The premonitory symptoms (prodrome): a tertiary care study of 893 migraineurs. Headache 2004; 44:865.
- Schulte LH, Jürgens TP, May A. Photo-, osmo- and phonophobia in the premonitory phase of migraine: mistaking symptoms for triggers? J Headache Pain 2015; 16:14.
- Cuvellier JC, Mars A, Vallée L. The prevalence of premonitory symptoms in paediatric migraine: a questionnaire study in 103 children and adolescents. Cephalalgia 2009; 29:1197.
- Cutrer FM, Huerter K. Migraine aura. Neurologist 2007; 13:118.
- Viana M, Linde M, Sances G, et al. Migraine aura symptoms: Duration, succession and temporal relationship to headache. Cephalalgia 2016; 36:413.
- Hansen JM, Lipton RB, Dodick DW, et al. Migraine headache is present in the aura phase: a prospective study. Neurology 2012; 79:2044.
- Hansen JM, Goadsby PJ, Charles A. Reduced efficacy of sumatriptan in migraine with aura vs without aura. Neurology 2015; 84:1880.
- Schürks M, Rist PM, Bigal ME, et al. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ 2009; 339:b3914.
- Barlow CF. Migraine in the infant and toddler. J Child Neurol 1994; 9:92.
- Virtanen R, Aromaa M, Rautava P, et al. Changing headache from preschool age to puberty. A controlled study. Cephalalgia 2007; 27:294.
- Gelfand AA, Reider AC, Goadsby PJ. Cranial autonomic symptoms in pediatric migraine are the rule, not the exception. Neurology 2013; 81:431.
- Eross E, Dodick D, Eross M. The Sinus, Allergy and Migraine Study (SAMS). Headache 2007; 47:213.
- Raieli V, Pitino R, Giordano G, et al. Migraine in a pediatric population: a clinical study in children younger than 7 years of age. Dev Med Child Neurol 2015; 57:585.
- Winner P, Rothner AD. Headaches in Children and Adolescents, BC Decker, Hamilton 2001.
- Stafstrom CE, Rostasy K, Minster A. The usefulness of children's drawings in the diagnosis of headache. Pediatrics 2002; 109:460.
- Mar S, Kelly JE, Isbell S, et al. Prevalence of white matter lesions and stroke in children with migraine. Neurology 2013; 81:1387.
- Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000; 55:754.
- Metsähonkala L. Migraine and nonmigrainous headache--how to distinguish them. Cephalalgia 1999; 19 Suppl 25:53.
- Rothner AD. Headaches in children and adolescents. Child Adolesc Psychiatr Clin N Am 1999; 8:727.
- Forsyth R, Farrell K. Headache in childhood. Pediatr Rev 1999; 20:39.
- Winner PK. Headaches in children. When is a complete diagnostic workup indicated? Postgrad Med 1997; 101:81.
- Practice parameter: the electroencephalogram in the evaluation of headache (summary statement). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 1995; 45:1411.
- Cortical spreading depression
- Role of serotonin
- Role of CGRP
- Right to left cardiac shunt
- CLINICAL FEATURES
- Premonitory phase
- Migraine aura
- Migraine headache phase
- Migraine postdrome
- Laboratory evaluation
- DIFFERENTIAL DIAGNOSIS
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS