The terms “migraine variant of childhood,” “paroxysmal disorder of childhood,” and “complicated migraine” are often used interchangeably in clinical practice. Migraine variants or precursors are age-related disorders that occur periodically and have variable neurologic dysfunction. They occur in children who often have other forms of migraines, strong family histories of migraines, or develop migraine at a late age. Complicated migraine, also known as “complex migraine” or “migraine accompagnee,” includes migraine syndromes with episodic, transient, and reversible neurologic dysfunction such as hemiparesis or altered level of consciousness. Many have previously been classified as migrainous aurae or other migraine subtypes.
Paroxysmal disorders are episodic phenomenon that do not fit into the other categories but are often confused with them and are included in their differential diagnoses; however, they need to be differentiated from them.
The phrase “periodic syndrome” is often used as a generic term to describe the above entities as “periods” of neurological dysfunction or symptomatology interspersed with periods of normalcy.
It must be noted that these conditions are diagnoses of exclusion. Underlying etiologies have to be sought whenever a patient presents with these symptoms. These patients should be free of symptoms of increased intracranial pressure. They should not have symptoms or signs of a progressive neurological disease. Their neurological examination should be normal between episodes. Laboratory testing, electroencephalogram (EEG), and neuroimaging are generally but not always nonrevealing.
This review presents useful clinical information concerning these syndromes that can be applied in the outpatient or emergency settings.
History and Epidemiology
The term “periodic syndrome” was first introduced by Wyllie and Schlesinger1 in 1933 to describe recurrent episodes of fever, headache, vomiting, and abdominal pain in childhood. In 1984, Barlow2 presented multiple examples of these phenomena. Since then, case reports, studies, and reviews have added to our knowledge.3–5
The frequency of these disorders has been noted to range from 6% to 24% among children ultimately diagnosed with migraine.6
The evaluation of periodic syndromes ranges from no tests when a syndrome is clearly and definitely recognized, to an in-depth and thorough evaluation when the etiology of the syndrome is not clear or when multiple treatments have been attempted with no avail.7,8
A list of migraine variants can be seen in Table 1.
Migraine Variants in Childhood
Recent articles have suggested that infantile colic should be considered a migraine variant.9,10 Colic is a common cause of inconsolable crying during the first few months of life. In studying children with migraines compared to children with no headaches or tension-type headaches, it was noted that the prevalence of colic in the migraine group was significantly higher than in the other groups.9 It was also noted that the mothers of infants with colic had a higher incidence of migraine than the noncolic control group. Additional longitudinal studies will be needed to confirm this hypothesis.
Benign Paroxysmal Torticollis
Benign paroxysmal torticollis was described by Snyder in 1969.11 It is an uncommon disorder seen in infants and young children. It consists of the sudden onset of recurrent episodes of head tilt commencing between ages 2 and 8 months. The spells are often associated with pallor, irritability, and vomiting. The episodes can be unprovoked or precipitated by illness. It may alternate sides and may last hours to days. The patient is well between attacks and developmental milestones are normally acquired. Some consider it a dyskinesia.12 The patients often have a family history of migraine or the patient may develop migraine in the future. Preventive medications are seldom used because the frequency of attacks is unpredictable. If the diagnosis is unclear, magnetic resonance imaging (MRI) of the brain may be performed to rule out a posterior fossa tumor. The condition often resolves by age 3 to 5 years, but it may be replaced by a different migraine variant or other form of migraine.12
Benign Paroxysmal Vertigo
Benign paroxysmal vertigo (BPV) was described by Basser13 in 1964. The mean age of onset is approximately age 3.5 years and resolution is typically around age 5.5 years.13 Cases of BPV have been noted to morph into other migraine variants or typical migraine attacks as the child gets older.12 Children affected with BPV are typically toddlers and present with recurrent spells of disabling vertigo not preceded by any warning and that last from seconds to minutes. There is no loss of consciousness. Pallor, nausea, and nystagmus occur variably. No headache is noted. The child appears normal after the attack. The frequency is variable and recurrences are unpredictable; therefore, medication is seldom used. The attacks decrease in frequency over several years and then disappear.14
Cyclic Vomiting Syndrome
Cyclic vomiting syndrome (CVS) is marked by recurrent and severe episodes of early morning vomiting that reappear at stereotypical intervals.15 CVS begins between ages 5 and 9 years and often ends at puberty.16 Patients may have early morning episodes accompanied by abdominal pain, anorexia, and nausea. They then vomit every 5 to 10 minutes (usually at least 6 times per hour).16 This continues for 6 to 12 hours only to reoccur in some patients the next day. Most children are well between the attacks. CVS is usually idiopathic, although many patients have a strong family history of migraine. Rarely, CVS can be the presenting manifestation of a metabolic disorder or other organic disease processes.3,17 Most children with CVS begin their search for a diagnosis with a gastroenterologist.
Many patients require intravenous hydration during the attack. Additional supportive therapy includes antiemetics and sedation. Triptans may be helpful in the acute phase. A variety of migraine prophylactic agents have been used, including cyproheptadine and topiramate. The disorder often, but not always, disappears at puberty.16
Abdominal migraine should be suspected in children with recurrent bouts of abdominal pain separated by pain-free intervals and a negative gastrointestinal evaluation.18 Many patients have a positive family history of migraine. In the past, it was also referred to as abdominal epilepsy, especially if the EEG showed benign focal epileptiform discharges. Children with daily or continuous abdominal pain do not have abdominal migraine. The pain of abdominal migraine lasts approximately 2 to 72 hours at a time, is located midline or in the periumbilical area, and is described as dull or sore in quality.19 Anorexia, nausea, vomiting, and pallor are common accompaniments. Headaches are variably present. The syndrome often improves after several years only to be replaced by typical migraine. The usual migraine prophylactic medications may be helpful. The age group typically affected is children age 3 to 12 years.
Complicated migraine syndromes are also known as complex migraine, and in Europe as “migraine accompagnee.”19 Complicated migraine includes syndromes with episodic, neurologic dysfunction that precede, accompany, or follow headache or occur in isolation without any accompanying head pain. These patients may also experience the usual forms of migraine. The International Classification of Headache Disorders considers hemiplegic migraine and basilar migraine as forms of migraine with aura.20 Ophthalmic and retinal migraines are migraine subtypes.20 These disorders may have their onset in children but can persist throughout life. The different types of complicated migraine are listed in Table 2.
Types of Complicated Migraine
Basilar Migraine (Migraine with Brainstem Aura)
Basilar migraine was first described by Bickerstaff21 in 1961. It consists of dysfunction referable to the brain stem, cerebellum, and parietal and occipital regions. Adolescents are frequently affected, although people at any age can experience this form of migraine. It is one of the more common periodic syndromes. It consists of a variety of unusual symptoms that may be bilateral or unilateral. Symptoms include vertigo, facial numbness, nausea, vomiting, quadriparesis, dysarthria, tinnitus, ataxia, alterations in vision, and/or loss of consciousness. The migranous headache follows the above symptoms and may be occipital in location, in contrast to most typical migraines, which are experienced in the frontal or temporal regions. Although neurological deficits are transient, a thorough evaluation, including EEG during the attack and MRI afterward, is needed. Standard migraine prophylaxis is commonly employed to decrease recurrences.20
Both sporadic and familial cases of hemiplegic migraine may occur.22 The condition is characterized by hemiplegia or hemiparesis, followed by a headache on the contralateral side. It may be caused by one of three channelopathaties.23 The face and arm are weaker than the legs during an attack. Alternate sides may be affected in subsequent attacks. Hemianopsia, sensory symptoms, confusion, and aphasia may occur along with motor weakness. The hemiparesis is not permanent but can last up to 72 hours.22 The differential diagnosis is extensive, and the evaluation at the time of initial presentation should be as well. Antiepileptic drugs and calcium channel blockers are often used to prevent further attacks. Extensive data regarding treatment and prognosis is lacking.23
Ophthalmoplegic migraine is the association with eye pain and a complete or incomplete third nerve palsy.24 The fourth or sixth nerves are rarely involved. The headache (eye pain) may last hours but the ophthalmoplegia may last weeks. Repeated attacks may cause a permanent deficit. MRI is needed to make sure there is no aneurysm compressing the third cranial nerve. MRI may show gadolinium enhancement of the third nerve, which confirms the diagnosis. Steroids may reduce the eye pain and shorten the duration of the ophthalmoplegia. Data regarding prophylaxes are not available.
Retinal migraine is also known as ophthalmic migraine or ocular migraine. It is a form of migraine sine (Latin for “without”) headache, although in some instances the visual symptoms can be followed by migraine-like pain within 1 hour of the visual symptoms. Patients experience episodic unilateral eye symptoms that are sudden and brief and may include scotomata, blindness, and/or positive phenomenon such as flashing lights or bright spots.25 There is a family history of migraine in most instances. Neurological and ophthalmological evaluations are normal except for the loss of vision. Sequelae are rare. Data regarding treatment are anecdotal.
Confusional migraine may occur in the setting of migraine with aura, hemiplegic migraine, and basilar migraine. It often occurs in teenagers with a history of migraine. It may begin with a headache followed by restlessness, confusion, agitation, and aggression, although in some children the headache follows the period of confusion.26 It may be provoked by mild head trauma. The syndrome may be recurrent. The child often has amnesia for the event. An EEG during the episode may reveal focal or generalized slowing. The patient often improves remarkably within 4 to 6 hours.26 A complete evaluation for a toxic encephalopathy is needed. If attacks are recurrent, prophylaxis is indicated.
Alice in Wonderland Syndrome
Alice in Wonderland syndrome is considered an unusual aura and can occur without a headache. It consists of bizarre visual illusions and spatial distortions, sometimes involving the child's own body.27 Children describe micropsia (objects appear unusually small), macropsia (objects appear large), and distortions of time and perception. There may not be confusion or altered awareness, and the child may clearly articulate these unusual visual distortions. Similar symptoms have been reported to occur in association with infectious mononucleosis, complex partial seizures, drug ingestion, and occipital epilepsy. Alice in Wonderland syndrome is named after the book's author, Lewis Carroll, who was believed to have suffered from migraine with aura.27
Alternating Hemiplegia of Childhood
Alternating hemiplegia of childhood is one of the rare periodic syndromes in which neurologic abnormalities may be progressive. Children as young as age 6 months may show symptoms.28 The patient is often well at the onset but after multiple attacks may develop permanent motor deficits and cognitive impairments. The patient has multiple episodes of hemiplegia that are often relieved by sleep. Occasionally, the affected body parts may exhibit dystonia or chorea. It may be a manifestation of mitochondrial and metabolic disorders, and a diagnosis of migraine should only be made after other etiologies have been ruled out.28 A calcium channel blocker may offer some benefits.
Trauma-triggered migraine, also known as “footballer's migraine,” is common in children and adolescents. It refers to attacks of migraines provoked by minor head trauma.29 Any form of migraine may occur (eg, migraine with aura or chronic migraine). In some patients, there is a latent period of 10 to 60 minutes after the trauma before the actual migraine attack.29 Complex migraine can also be provoked by head trauma, and if this occurs then more serious underlying problems, such as concussion and a subdural or epidural hematoma, must be considered. If a patient has posttraumatic neurologic dysfunction, urgent evaluation is needed. If spells are frequent, discontinuation of contact sports should be considered. Please see the review on posttraumatic headache for further information regarding this entity (see Langdon and Taraman30).
Epilepsy Equivalent Syndrome
Epilepsy equivalent syndrome speaks to the close relationship between migraine and epilepsy. The term “migralepsy” is sometimes used to describe this ambiguous zone that overlaps these clinical entities. The association of a clinical event that resembles migraine, with or without altered or loss of consciousness but with an abnormal concurrent EEG showing epileptiform discharges, is suggestive of the diagnosis.31 Benign familial epileptiform discharges of childhood are common in children and adolescents with migraine and raise questions about true epilepsy or an incidental abnormality.32 Prolonged EEG monitoring and capturing a spell may be diagnostic, as during an episode a true seizure can be clearly demonstrated on scalp EEG recordings.
Migraine Sine Hemicrania
Migraine sine hemicrania refers to migrainous phenomena not followed by or associated with headache. It seems to be more frequent in adults. The more common variety consists of a typical visual aura with no headache, sometimes described as visual “snow.” The aura usually lasts less than 10 minutes at a time.33 The episodes are recurrent. Patients frequently have usual migraine attacks at other times. Typical prophylactic medications can be helpful.
Vestibular migraine is the association of dizziness or vertigo with migraine, either at the time of a migraine episode or at an unrelated time.33 It is estimated to occur in 9% of migraine patients.34 It lasts from minutes to hours and can be disabling. The presence of headache with the vertigo is variable, making the diagnosis difficult for the clinician. Nonpharmalogical, mechanical (such as vestibular rehabilitation measures), and medication approaches are used. Some patients may be refractory to therapy.
Some of the disorders discussed in this article are not rare, and they will likely be encountered by all pediatric providers at some point in their clinical practice. When confronted with a recurrent episodic disorder, even if there is no headache, it is important to think migraine variant, complex migraine, or periodic disorder. Not all children need to be evaluated by a specialist, but many will require investigations such as imaging to rule out other underlying disorders.
- Wyllie WG, Schlesinger B. The periodic group of disorders in childhood. Br J Child Dis. 1933;30:1–21.
- Barlow CF. Headaches and Migraine in Childhood. Philadelphia, PA: JB Lippincott; 1984:93–125.
- Rothner A, Parikh S. Migraine variants or episodic syndromes that may be associated with migraine and other unusual pediatric headache syndromes. Headache. 2016;56(1):206–214. doi:. doi:10.1111/head.12750 [CrossRef]
- Lagman-Bartolome AM, Lay C. Pediatric migraine variants: a review of epidemiology, diagnosis, treatment, and outcome. Curr Neurol Neurosci Rep. 2015;15(6):34. doi:. doi:10.1007/s11910-015-0551-3 [CrossRef]
- Lewis D. Migraine and migraine variants in childhood and adolescence. Semin Pediatr Neurol. 1995;2(2):127–143. doi:10.1016/S1071-9091(05)80023-3 [CrossRef]
- Al-Twaijri WA, Shevell MI. Pediatric migraine equivalents: occurrence and clinical features in practice. Pediatric Neurol. 2002;26(5):365–368. doi:10.1016/S0887-8994(01)00416-7 [CrossRef]
- Cleves-Bayon C, Rothner AD. Diagnosis of headache in children and adolescents. In: Tepper S, Tepper D, eds. The Cleveland Clinic Manual of Headache Therapy. New York, NY: Springer; 2014:115–126. doi:10.1007/978-3-319-04072-1_8 [CrossRef]
- Cleves-Bayon C, Rothner AD. Episodic syndromes that may be associated with migraine, pediatric tension-type headache, chronic daily headache syndromes in children and pediatric idiopathic intracranial hypertension. In: Tepper S, Tepper D, eds. The Cleveland Clinic Manual of Headache Therapy. New York, NY: Springer; 2014:127–142. doi:10.1007/978-3-319-04072-1_9 [CrossRef]
- Romanello S, Spiri D, Marcuzzi E, et al. Association between childhood migraine and history of infantile colic. JAMA. 2013;309(15):1607–1612. doi:. doi:10.1001/jama.2013.747 [CrossRef]
- Gelfand AA, Goadsby PJ, Allen IE. The relationship between migraine and infant colic: a systematic review and meta-analysis. Cephalalgia. 2015;35(1):63–72. doi:. doi:10.1177/0333102414534326 [CrossRef]
- Snyder CH. Paroxysmal torticollis in infancy. Am J Dis Child. 1969;117(4):458–460. doi:10.1001/archpedi.1969.02100030460013 [CrossRef]
- Rosman NP, Douglass LM, Sharif UM, Paolini J. The neurology of benign paroxysmal torticollis of infancy: report of 10 new cases and review of the literature. J Child Neurol. 1998;19:236–238.
- Basser LS. Benign paroxysmal vertigo of childhood. Brain. 1964;87(1):141–152. doi:10.1093/brain/87.1.141 [CrossRef]
- Lindskog U, Odkvist L, Noaksson L, Wallquist J. Benign paroxysmal vertigo in childhood: a long-term follow-up. Headache. 1999;39(1):33–37. doi:10.1046/j.1526-4610.1999.3901033.x [CrossRef]
- Li BU, Lefevre F, Chelimsky GG, et al. North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition consensus statement on the diagnosis and management of cyclic vomiting syndrome. J Pediatr Gastroenterol Nutr. 2008;47(3):379–393. doi:. doi:10.1097/MPG.0b013e318173ed39 [CrossRef]
- 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):569–573. doi:. doi:10.1016/j.pediatrneurol.2014.02.009 [CrossRef]
- Boles RG, Lovett-Barr MR, Preston A, Li BU, Adams K. Treatment of cyclic vomiting syndrome with co-enzyme Q10 and amitriptyline, a retrospective study. BMC Neurol. 2010;10(1):10. doi:. doi:10.1186/1471-2377-10-10 [CrossRef]
- Dignan F. The prognosis of childhood abdominal migraine. Arch Dis Child. 2001;84(5):415–418. doi:10.1136/adc.84.5.415 [CrossRef]
- Carson L, Lewis D, Tsou M, et al. Abdominal migraine: an under-diagnosed cause of recurrent abdominal pain in children. Headache. 2011;51(5):707–712. doi:. doi:10.1111/j.1526-4610.2011.01855.x [CrossRef]
- Rothner AD. Complicated migraine and migraine variants. Semin Pediatr Neurol. 2001;8(1):7–12. doi:10.1053/spen.2001.23326 [CrossRef]
- Bickerstaff E. Basilar artery migraine. Lancet. 1961;277(7167):15–17. doi:10.1016/S0140-6736(61)92184-5 [CrossRef]
- Bradshaw P, Parsons M. Hemiplegic migraine: a clinical study. QJM. 1964;133:65–85.
- Gardner K, Barmada MM, Ptacek LJ, Hoffman EP. A new locus for hemiplegic migraine maps to chromosome 1q31. Neurology. 1997;49(5):1231–1238. doi:10.1212/WNL.49.5.1231 [CrossRef]
- Kandt RS. Steroid-responsive ophthalmoplegia in a child. Arch Neurol. 1985;42(6):589–591. doi:10.1001/archneur.1985.04060060095016 [CrossRef]
- Carroll D. Retinal migraine. Headache. 1970;10(1):9–13. doi:10.1111/j.1526-4610.1970.hed1001009.x [CrossRef]
- Gascon G, Barlow CF. Juvenile migraine presenting as acute confusional states. Pediatrics. 1970;45:628–635.
- Golden GS. Alice in Wonderland syndrome. Pediatrics. 1979;65:517–519.
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- Kossoff EH, Andermann F. Migraine and epilepsy. Semin Pediatr Neurol. 2010;17(2):117–122. doi:. doi:10.1016/j.spen.2010.04.005 [CrossRef]
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Migraine Variants in Childhood
Benign paroxysmal vertigo
Types of Complicated Migraine
Alice in Wonderland syndrome
Transient global amnesia35
Alternating hemiplegia of childhood