Migraine without Aura

Migraine without aura is the most common form of migraine in both children and adults. The ICHD-II (see Table 588-2) requires this to be recurrent (at least 5 headaches that meet the criteria, but there is no time limit over which this must occur). The recurrent episodic nature helps differentiate this from a secondary headache, as well as separates migraine from tension-type headache, but may limit the diagnosis in children as they may just be beginning to have headaches.

The duration of the headache is defined as 4-72 hr for adults. It has been recognized that children may have shorter duration headaches, so an allowance has been made to reduce this duration to 2-72 hr or 1-72 hr with diary confirmation. Note that this duration is for the untreated or unsuccessfully treated headache. Furthermore, if the child falls asleep with the headache, the entire sleep period is considered part of the duration. These duration limits help differentiate migraine from both short duration headaches, including the trigeminal autonomic cephalalgias, and prolonged headaches, like those due to pseudotumor cerebri. Some prolonged headaches may still be migraine, but a migraine that persists beyond 72 hr is classified as a variant termed status migrainosus.

The quality of migraine pain is often, but not always, throbbing or pounding. This may be difficult to elicit in young children and drawings or demonstrations may help confirm the throbbing quality.

The location of the pain has classically been described as unilateral (hemicrania); in children it is more commonly bilateral. A more appropriate way to think of the location would therefore be focal in location to differentiate it from the diffuse location of tension-type headaches. Of particular concern is the exclusively occipital headache as, although these can be migraines, they are more frequently secondary to another, more proximate etiology.

Migraine, when allowed to fully develop, often worsens in the face of and secondarily results in altered activity level. This has been classically identified in adults as resulting from worsening of pain when, for example, going up or down stairs. This history is often not elicited in children. A change in the child’s activity pattern, however, can be easily observed by a reduction in play or physical activity. For older children, sports or exercise may be limited or restricted during a headache attack.

Migraine may have a variety of associated symptoms. In younger children, nausea and vomiting may be the most obvious symptoms and often outweigh the headache itself. This often leads to the overlap with several of the gastrointestinal periodic diseases, including recurrent abdominal pain, recurrent vomiting, cyclic vomiting, and abdominal migraine. The commonality of all of these related conditions is an increased propensity for the later development of migraine. Oftentimes, early childhood recurrent vomiting may in fact be migraine, but the child is not asked about headache pain or is unable to describe headache pain. Once this becomes clear, the earlier diagnosis of a gastrointestinal disorder is no longer appropriate. When headache is present, vomiting raises the concern of a secondary headache, particularly related to increased intracranial pressure. One of the red flags for this is the daily or near daily early morning vomiting that increases in intensity as the intracranial pressure continues to build. When the headache with vomiting episodes are episodic and not worsening, it is more likely that the diagnosis is migraine. Vomiting and headache due to increased intracranial pressure are frequently present on first awakening and remit with maintenance of upright posture. In contrast, if a migraine is present on first awakening (a relatively infrequent occurrence in children), getting up and going about normal, upright activities usually makes the headache and vomiting worse.

As the child ages, light and sound sensitivity (photophobia and phonophobia) may become more apparent. This is either by direct report of the patient, or the interpretation by the parents of the child’s activity. These symptoms are likely a component of the hypersensitivity that develops during an acute migraine attack and may also include smell sensitivity (osmophobia) and touch sensitivity (cutaneous allodynia with central sensitization). Although only the photophobia and phonophobia are components of the ICHD-II criteria, these other symptoms are helpful in confirming the diagnosis and may be helpful in understanding the underlying pathophysiology and determining the response to treatment.

The final ICHD-II requirement is the exclusion of causes of secondary headaches, and this should be an integral component of the headache history.

Although not part of the ICHD-II criteria, it has been recognized migraine typically runs in families with reports up to 90% of children having a first- or second-degree relative with recurrent headaches. Given the underdiagnosis and misdiagnosis in adults, this is often not recognized by the family and a headache family history is required. When a family history is not identified, this may be due to either unawareness of migraine within the family or an underlying secondary headache in the child. Any child whose family, upon close and both direct and indirect questioning, does not include individuals with migraine or related syndromes (e.g., motion sickness, cyclic vomiting, menstrual headache), should have an imaging procedure performed to look for anatomic etiologies for headache.

In addition to the classifying features, there may additional markers of a migraine disorder. These include such things as triggers (skipping meals, inadequate or irregular sleep, dehydration and weather changes are the most common), pattern recognition (associated with menstrual periods in adolescents or Monday morning headaches due to change in sleep patterns over the weekend and nonphysiologic early waking on Monday mornings for school), and prodromes (a feeling of irritability, tiredness, and food cravings prior to the start of the headache). Although these additional features may not be consistent, they do raise the index of suspicion for migraine and provide a potential mechanism of intervention. In the past, food triggers were considered widely common, but the majority of these have either been discredited with scientific study or represent such a small number of patients that they only need to be addressed when consistently triggering the headache.

Migraine with Aura

The aura associated with migraine is a neurologic warning that a migraine is going to occur. In the common forms this can be the start of a typical migraine or a headache without migraine, or it may even occur in isolation. For a typical aura, the aura needs to be visual, sensory, or dysphasic, lasting longer than 5 min and less than 60 min with the headache starting within 60 min (see Table 588-2). The importance of the aura lasting longer than 5 min is to differentiate the migraine aura from a seizure with a postictal headache, while the 60 min maximal duration is to separate migraine aura from the possibility of a more prolonged neurologic event such as a transient ischemic attack.

The most common type of visual aura in children and adolescents is photopsia (flashes of light or light bulbs going off everywhere). These photopsias are often multiple colored and when gone, the child may report not being able to see where the flash occurred. Less likely in children are the typical adult auras including fortification spectra (brilliant white zigzag lines resembling a starred pattern castle) or shimmering scotoma (sometimes described as a shining spot that grows or a sequined curtain closing). In adults the auras typically involve only half the visual field, while in children they may be randomly dispersed. Blurred vision is often confused as an aura, but is difficult to separate from photophobia or difficulty concentrating during the pain of the headache.

Sensory auras are less common. They typically occur unilaterally. Many children describe this sensation as insects are worms crawling from their hand, up their arm to their face with a numbness following this sensation. Once the numbness occurs, the child may have difficulty using the arm as they have lost sensory input, and a misdiagnosis of hemiplegic migraine may be made.

Dysphasic auras are the least common type of typical aura and have been described as an inability or difficulty to respond verbally. The patient afterwards will describe an ability to understand what is being asked, but cannot answer back. This may be the basis of what in the past has been referred to a confusional migraine and special attention needs to be paid to asking the child about this possibility and their degree of understanding during the initial phases of the attack.

Much less commonly, atypical forms of aura can occur, including hemiplegia (true weakness, not numbness, and may be familial), vertigo or lower cranial nerve symptoms (basilar-type, formerly thought to be due to basilar artery dysfunction, now thought to be more brainstem based), and distortion (Alice in Wonderland syndrome). Whenever these rarer forms of aura are present, further investigation is warranted.

Hemiplegic migraine is one of the better known forms of rare auras. This transient unilateral weakness usually lasts only a few hours, but may persist for days. Both familial and sporadic forms have been described. The familial hemiplegic migraine (FHM) is an autosomal dominant disorder with mutations described in 3 separate genes: (1) CACNA1A, (2) ATP1A2, and (3) SCN1A. Multiple polymorphisms have been described for these genes.

Basilar-type migraine was formerly considered a disease of the basilar artery as many of the unique symptoms were attributed to dysfunction in this area of the brainstem. Some of the symptoms described include vertigo, tinnitus, diplopia, blurred vision, scotoma, ataxia, and an occipital headache. The pupils may be dilated, and ptosis may be evident.

HaNDL (transient headache with neurologic deficits, CSF pleocytosis) is considered a pseudomigraine syndrome.

Childhood periodic syndromes are a group of potentially related symptoms that occur in increased frequency in children with migraine. The hallmark of these symptoms is the recurrent episodic nature of the events. Some of these have included gastrointestinal-related symptoms (motion sickness, recurrent abdominal pain, recurrent vomiting including cyclic vomiting, and abdominal migraine), sleep disorders (sleepwalking, sleep-talking, and night terrors), unexplained recurrent fevers, and even seizures.

The gastrointestinal symptoms span the spectrum from the relatively mild (motion sickness on occasional long car rides) to severe episodes of uncontrollable vomiting that may lead to dehydration and the need for hospital admission to receive fluids. These latter episodes may occur on a predictable time schedule and hence have been called cyclic vomiting. During these attacks, the child may appear pale and frightened but does not lose consciousness. After a period of deep sleep, the child awakens and resumes normal play and eating habits as if the vomiting had not occurred. Many children with cyclic vomiting have a positive family history of migraine, and as they grow older have a high association with the development of migraine. Cyclic vomiting may be responsive to migraine-specific therapies with careful attention to fluid replacement if the vomiting is excessive. Cyclic vomiting of migraine must be differentiated from gastrointestinal disorders including intestinal obstruction (malrotation, intermittent volvulus, duodenal web, duplication cysts, superior mesenteric artery compression, internal hernias), peptic ulcer, gastritis, giardiasis, chronic pancreatitis, and Crohn disease. Abnormal gastrointestinal motility and pelviureteric junction obstruction can also cause cyclic vomiting. Metabolic causes include disorders of amino acid metabolism (heterozygote ornithine transcarbamylase deficiency), organic acidurias (propionic acidemia, methylmalonic acidemia), fatty acid oxidation defects (medium-chain acyl-CoA dehydrogenase deficiency), disorders of carbohydrate metabolism (hereditary fructose intolerance), acute intermittent porphyria, and structural central nervous system (CNS) lesions (posterior fossa brain tumors, subdural hematoma or effusions).

The diagnosis of abdominal migraine can be confusing, but can be thought of as a migraine without the headache. Like a migraine, it is an episodic disorder characterized by mid-abdominal pain with pain-free periods between attacks. At times this pain can be associated with nausea and vomiting (thus crossing into the recurrent abdominal pain or cyclic vomiting spectrum). The pain is usually described as “dull” and may be moderate to severe. The pain may persist from 1 to 72 hr and, although usually midline, may be periumbilical or poorly localized by the child. To meet the criteria of abdominal migraine, the child must complain at the time of the abdominal pain of at least 2 of the following: anorexia, nausea, vomiting, or pallor. As with cyclic vomiting, a thorough history and physical examination with appropriate laboratory studies must be completed to rule out an underlying gastrointestinal disorder as a cause of the abdominal pain. Careful questioning about the presence of headache or head pain needs to be addressed directly with the child, as many times this is truly a migraine, but in the child’s mind (as well as the parents’ observation) the abdominal symptoms are paramount.

Acute Treatment

Management of an acute attack is to provide headache freedom as quickly as possible with return to normal function. This mainly includes 2 groups of medicines: nonsteroidal antiinflammatory drugs (NSAIDs) and triptans. Most migraine headaches in children will respond to appropriate doses of NSAIDs when administered at the onset of the headache attack. Ibuprofen has been the most well documented at a dose of 7.5-10 mg/kg. Special concerns for the use of ibuprofen or other NSAIDs is ensuring that the children can recognize and respond to onset of the headache. This includes discussing the importance of telling the teacher when the headache starts at school and ensuring that proper dosing guidelines and permission have been provided to the school. In addition, overuse needs to be avoided, limiting the NSAID (or any combination of over-the-counter [OTC] analgesics) to not more that 2-3 times per week. If ibuprofen is not effective, naproxen sodium may also be tried in similar doses, and for older children (>15 yr old) aspirin may be effective. The goal of the primary acute medication should be headache relief within 1 hr with return to function in 10 out of 10 headaches.

When a migraine is especially severe, NSAIDs alone may not be sufficient. In this case a triptan may be considered. Currently, only almotriptan has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of acute migraine in adolescents (age 12-17 yr). There have been multiple studies that have demonstrated their effectiveness and tolerability. The difficulty with these studies was that effectiveness of the triptans was the same as in adults, but the placebo effectiveness rate was higher than in studies with an “adult design.” For most adolescents, dosing is the same as for adults; a reduction in dose is made for small adolescents or younger children. The triptans vary by rapidity of onset and biologic half-life. This is related to both their variable lipophilicity and dose. Clinically, 60-70% of patients respond to the 1st triptan tried, with 60-70% of the patients that did not respond to the 1st triptan responding to the next triptan. Therefore, in the patient who does not respond to the 1st triptan in the desired way (rapid reproducible response without relapse or side effects), it is worthwhile to try a different triptan. The most common side effects of the triptans are due to their mechanism of action—tightness in the jaw, chest, and fingers due to vascular constriction and a subsequent feeling of grogginess and fatigue due to the central serotonin effect. The vascular constriction symptoms can be alleviated through adequate fluid hydration during an attack.

The most effective way to administer the NSAIDs and triptans is to use the NSAIDs first, restricting their use to fewer than 2-3 times per wk, and adding the triptan for moderate to severe attacks, restricting their use to not more than 4-6 times per mo.

As vascular dilatation is a common feature of migraine that may be responsible for some of the facial flushing followed by paleness and the lightheaded feeling accompanying the attacks, fluid hydration should be integrated into the acute treatment plan. For oral hydration this can include the sports drinks that combine electrolytes and sugar to provide the intravascular rehydration.

In the past, antiemetics were used for acute treatment of the nausea and vomiting. Further study has identified that their unique mechanism of effectiveness in headache treatment is related to their antagonism of dopaminergic neurotransmission. Therefore, the antiemetics with the most robust dopamine antagonism (i.e., prochlorperazine and metoclopramide) have the best efficacy. These can be very effective for status migrainosus or a migraine that is unresponsive to the NSAIDs and triptans. They require intravenous administration, as other forms of administration of these drugs are less effective than the NSAIDs or triptans. When combined with ketorolac and intravenous fluids in the emergency department or an acute infusion center, intravenous antiemetics can be very effective. When they are not effective, further inpatient treatment may be required using dihydroergotomine (DHE).

Preventive Therapy

When the headaches are frequent (≧1/wk) or disabling (missing school, home, or social activities, or a PedMIDAS score above 20), preventive or prophylactic therapy is warranted. The goal of this therapy should to be to reduce frequency (1-2 headaches or fewer per mo) and disability (PedMIDAS <10). Prophylactic agents should be given for at least 4-6 mo at an adequate dose and then weaned over several weeks’ time. Evidence in adult studies has begun to demonstrate that persistent frequent headaches foreshadow an increased risk of progression with decreased responsiveness and increased risk of refractoriness in the future. It is unclear if this also occurs in children and/or adolescents and if early treatment of headache in childhood prevents development of refractory headache in adulthood.

Multiple preventive medications have been utilized for migraine prophylaxis in children. When analyzed as part of a practice parameter, only one medication—flunarizine—was demonstrated to reach a level of effectiveness viewed as substantial and it is not available in the USA. Flunarizine is typically dosed at 5 mg orally daily and increased after 1 mo to 10 mg orally daily, with a month off of drug every 4-6 mo.

The most commonly used preventive therapy for headache and migraine is amitriptyline. It was first used for this purpose in the 1970s and has subsequently been used worldwide as one of the first-line preventive agents. Typically a dose of 1 mg/kg daily at dinner or in the evening is effective. However, this dose needs to be reached slowly (i.e., over weeks) to minimize side effects and improve tolerability. The most common side effects are those related to amitriptyline’s anticholinergic activity and sleepiness. Weight gain has been observed in adults using amitriptyline but is less frequent in children. Amitriptyline does have the potential to exacerbate prolonged QT syndrome, so it should be avoided in patients with this diagnosis and looked for in patients on the drug who complain of rapid or irregular heart rate.

Antiepileptic medications are more recently commonly used for migraine prophylaxis, with topiramate, valproic acid, and levetiracetam having been demonstrated to be effective in adults. There are limited studies in children for migraine prevention, but all of these medications have been assessed for safety and tolerability in children with epilepsy.

Topiramate has become widely used for migraine prophylaxis in adults. Topiramate has also been demonstrated to be effective in an adolescent study. This study demonstrated that a 25-mg dose twice a day was equivalent to placebo, while a 50-mg dose twice a day was superior. Thus it appears that the adult dosing schedule is also effective in adolescents with an effective dosage range or 50 mg twice a day to 100 mg twice a day. This dose needs to be reached slowly to minimize the cognitive slowing associated with topiramate use. Additional side effects include weight loss, paresthesias, kidney stones, lowered bicarbonate levels, decreased sweating, and rarely glaucoma and changes in serum transaminases. In addition, in adolescent girls taking birth control pills the lowering of the effectiveness of the birth control by topiramate needs to be discussed.

Valproic acid has long been used for epilepsy in children and has been demonstrated to be effective in migraine prophylaxis in adults. The effective dose in children appears to be 10 mg/kg orally twice a day. Side effects of weight gain, ovarian cysts, and changes in serum transaminases and platelet counts need to be monitored.

Other antiepileptics including lamotrigine, levetiracetam, zonisamide, gabapentin, and pregabalin have also been used for migraine prevention.

β-Blockers have also been used for migraine prevention. The studies on β-blockers have a mixed response pattern with variability both between β-blockers and between patients with a given β-blocker. Propranolol has been the best studied for pediatric migraine prevention with unequivocally positive results. The contraindication for use of propranolol in children with asthma or allergic disorders or diabetes and the increased incidence of depression in adolescents using propranolol limit its use somewhat. It may be very effective for a mixed subtype of migraine (basilar-type migraine with postural orthostatic tachycardia syndrome [BAM-POTS]). This syndrome has been reported to be responsive to propranolol.

In very young children, cyproheptadine may be effective in prevention of migraine or the related variants. Young children tend to tolerate the increased appetite induced by the cyproheptadine and tend not to be subject to the lethargy seen in older children and adults; the weight gain is limiting once children start to enter puberty. Typical dosing is 0.1 to 0.2 mg/kg orally twice a day.

Biobehavioral Therapy

Biobehavioral evaluation and therapy is essential for effective migraine management. This includes identification of behavioral barriers to treatment, like a child’s shyness or limitation in notifying a teacher of the start of a migraine or a teacher’s unwillingness to accept the need for treatment. Additional barriers include a lack of recognition of the significance of their headache problem and reverting to “bad habits” once the headaches have responded to treatment. Adherence is equally important for acute and preventive treatment. The need to have a sustained response for long enough to prevent relapse (i.e., to stay on preventive medication) is often difficult when the child starts to feel better. Having a defined end-point and duration (1-2 or fewer headaches per mo for 4-6 mo) helps with acceptance.

As many of the potential triggers for frequent migraines (skipping meals, dehydration, decreased or altered sleep) are related to a child’s daily routine, a discussion of healthy habits is a component of biobehavioral therapy. This should include adequate fluid intake without caffeine, regular exercise, not skipping meals and making healthy food choices, and adequate (8-9 hr) sleep on a regular basis. Sleep is often difficult in adolescents, as middle and high schools often have very early start times, and the adolescent’s sleep architecture features a shift to later sleep onset and waking. This has been one of the explanations for worsening headaches during the school years in general and at the beginning of the school year and week.

Biofeedback-assisted relaxation therapy has been demonstrated to be effective for both acute and preventive therapy and may be incorporated into this multiple treatment strategy. This provides the child with a degree of self-control over the headaches and may further help the child cope with frequent headaches.