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Parkinson’s disease (PD) is a complex neurodegenerative condition that predominantly affects older people, with a rising prevalence worldwide.1,2 There are many on-going challenges and unmet needs in PD: difficulties in making an accurate diagnosis (particularly in the early stages of the disease), troubling side effects associated with the available pharmacological treatments, a lack of effective disease-modifying therapies […]

Diagnosis and Treatment of Pediatric Migraine

Jack Gladstein
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Published Online: Jun 4th 2011
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Abstract

Overview

The diagnosis of pediatric migraine is easily made on the basis of a good history and a benign physical examination. Severe pain, nausea or vomiting, and photophobia or phonophia may be quite alarming to a youngster and his or her family. Parents are convinced that their child has a tumor, so addressing those fears must become part of the visit. Ironically, this is usually good news, since most of the time the symptoms will end up being those of migraine. Once a diagnosis of migraine is made, the physician can focus on the impact of headache on home life, work environment, and social interactions. All headache fits into four distinctive patterns. Rothner s model divides headache into acute, acute recurrent, chronic progressive, and chronic non-progressive (see Figure 1).1 Time is measured in days on the X axis and severity of headache is measured on an arbitrary scale on the Y axis. Migraine is the main culprit of headaches that fit into the acute recurrent pattern.

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Article

Migraine Diagnosis
In a landmark study2 in adults, patients with a chief complaint of migraine had a final diagnosis of migraine. Patients with a chief complaint of sinus headache had a diagnosis of migraine, and patients with a chief complaint of tension headache left with a diagnosis of migraine. In fact, 94% of adults presenting with a headache as their chief complaint had migraine. What this shows is that migraine is prevalent and under-diagnosed. In the Lipton population study,3 migraine was under-diagnosed by about 50%, yet the diagnosis is very easy. Adults need to experience more than five episodes of headache lasting from four to 72 hours with nausea or vomiting, photophobia and phonophobia, and inability to perform strenuous exercise. Pain is unilateral, but does not necessarily need to be. Even easier is bad pain with autonomic symptoms, which is migraine. Positive family history and need to rest support this diagnosis. Note that location is not mentioned: although classic teaching classifies headache as a unilateral frontal phenomenon, most headaches can be bilateral, temporal, occipital, or holocranial. Childhood migraine differs from adult migraine in that headache is shorter (1 72 hours) and more often bilateral.4 Further, children do not describe their pain well, so using expressions such as knife-like, throbbing, and vise-like are irrelevant for most youngsters they just say it hurts.5 When obtaining family history, it is important to ask if the affected family members had headache, not migraine, since other family members may have been misdiagnosed as well. In order to establish degree of disability during an attack, ask the patient if he or she could run up and down the stairs a few times during an episode. Migraine is a disease of young people, with peak prevalence in the first few decades of life.6,7 Migraine can be with or without aura; most children, however, have migraine without aura. Migraine aura, when present, is usually stereotypical.

A migraine attack can begin with a warning: patients may feel sluggish or hungry or have some word-finding difficulties that they will report in retrospect. There is a feeling of doom similar to that seen in seizure patients. An aura, however, is a memorable phenomenon. Wavy lines, beginning peripherally, move across the visual field, usually sparing the midline. This has been coined fortification spectra, since forts were built with jagged outpouchings to protect a larger periphery. Headache usually begins approximately 30 minutes after the onset of the visual aura. Migraine with aura is an easy diagnosis, but most pediatric migraineurs do not present with aura.4 Migraine without aura is just as easy if you stick to the paradigm acute recurrent headache that stops what you are doing, and has autonomic symptoms. Other common autonomic symptoms include dizziness, lightheadedness, pallor, or purple bags around the eyes. Ask the parent if he or she can tell just by looking that the child has a headache.

A migraine attack can begin with a warning: patients may feel sluggish or hungry or have some word-finding difficulties that they will report in retrospect. There is a feeling of doom similar to that seen in seizure patients. An aura, however, is a memorable phenomenon. Wavy lines, beginning peripherally, move across the visual field, usually sparing the midline. This has been coined fortification spectra, since forts were built with jagged outpouchings to protect a larger periphery. Headache usually begins approximately 30 minutes after the onset of the visual aura. Migraine with aura is an easy diagnosis, but most pediatric migraineurs do not present with aura.4 Migraine without aura is just as easy if you stick to the paradigm acute recurrent headache that stops what you are doing, and has autonomic symptoms. Other common autonomic symptoms include dizziness, lightheadedness, pallor, or purple bags around the eyes. Ask the parent if he or she can tell just by looking that the child has a headache.

In all forms of childhood migraine, time of day is not that helpful. Some patients routinely awaken in the middle of the night, some get worse as the day goes on, and some have no particular predictable pattern. Triggers vary from person to person and a long list of triggers has been implicated.9 One can tell patients that as a migraineurs, they are more susceptible to triggers in effect, they have a sensitive autonomic system that responds to triggers with migraine. Headache sufferers need to eat, exercise, and sleep regularly. School is a tremendous trigger. School stressors include waking up too early, worrying about grades, bullying, undiagnosed learning disabilities, and pressure from parents, to name but a few.10,11 Some foods to avoid include caffeine, monosodium glutamate (MSG), chocolate, cheese, and sulfites. However, adhering to this diet is onerous. An elimination trial is a better option for most, where one type of food is eliminated and then a judgment is made about whether this caused a difference. If not, the potentially migrainogenic food can be reintroduced in moderation.12 Migraineurs have a heightened sensitivity to flickering lights in the room, startle more easily, and have more sensitive skin interictally.13 They also have more gastroparesis even when not having a headache.14During a migraine attack, if left to his- or herself a child or adolescent with migraine will want to retreat to a dark and quiet place in an attempt to decrease external stimulation, and will often want to lie down. This is very difficult to accomplish in the school setting. In the past, treatment was to help children get to sleep. Now, with the advent of triptan medication, youngsters should go back to work or school as part of their treatment plan. The co-operation of school nurses is crucial in allowing the child to have access to medication at the first twinge of headache, and then be able to rest for a short while before returning to class.15 Making the diagnosis of migraine by history should just take a few moments. One can then focus on disability— how have the headaches affected the patient and his or her family? Objective measures include the number of days of school missed, but other markers of disability include family function, curtailment of enjoyable activities, and a general description of what happens at home when the patient gets a headache. The Peds-MIDAS Scale can generate a disability score that can be tracked over time.16,17 A more subtle question is how many days is the youngster in school but not performing at 100% due to headaches.

Physical examination reassures both clinician and patient while making sure that nothing important is missed. Patients should be undressed and examined in a gown with underwear off, since a careful inspection for café au lait spots and scoliosis may hint at intracranial pathology. Vital signs will help discover patients with hypertension, as well as the dreaded Cushing’s triad. The rest of the physical is standard. A thorough neurological examination is indicated. Luckily, there are few surprises: if a story consistent with migraine is presented and the examination is normal, there is no need for further work-up.18,19

Diagnostic Pitfalls

Sinus versus Migraine
Since the second branch of the trigeminal nerve innervates the nose, eyes, and maxillary sinus areas, a migraine can sometimes cause lacrimation, rhinorrhea, and/or sinus tenderness. If there are autonomic symptoms and the pattern is acute and recurrent, the diagnosis is migraine, not sinus disease. Sinus disease presents as fever, cough, and halitosis. It does not remit and return like migraine does.20,21 This mistake might cause the pediatric practitioner to prescribe amoxicillin instead of triptan.

Figure 1: Classification of Headache
Adapted from Rothner AD, Semin Pediatr Neurol, 2001;8:2–6.

Chiari Malformation
As many as 10% of ‘normals’ have Chiari malformation on magnetic resonance imaging (MRI), so 10% of migraineurs would also have the radiological diagnosis. This is an argument against scanning all headache patients. Symptomatic Chiari requiring neurosurgical intervention involves tingling of hands and feet during headache, or headache consistently being posterior in location.22 If real Chiari is suspected, more sensitive MRI flow studies can pick up the obstruction. Also, one should look for a syrinx a little lower in the spine.23 Treatment of Migraine
Migraine treatment can be divided into acute treatment, preventive treatment, and general migraine hygiene.

Acute Migraine Treatment
Acute migraine treatment is a race against the clock to prevent cutaneous allodynia. In the early phases of migraine, it is an easy problem to treat and can respond to generous doses of over-the-counter pain medicine. However, when a migraine gathers steam, it moves from a peripheral to a central event and becomes harder to treat as more inflammation develops.24 Recruitment of central neurons causes cutaneous allodynia. A patient will say that his or her hair hurts, or that he or she cannot keep glasses on or keep the coat on the shoulders. Triptans do not work as well once central sensitization occurs.25 A recent report from Italy showed that children admitted for migraine have allodynia.26 Over-the-counter drugs—such as ibuprofen, acetaminophen, naproxen sodium, etc.—do have a role: they are generally prostaglandin inhibitors and mitigate inflammation. They have a role early in a headache while the stomach is still working properly; however, once nausea is present their efficacy dwindles. The ‘pearl’ is to use higher doses of these drugs, assuming some gastroparesis has already taken place. Parents are reluctant to use higher doses of these and all medications. A wonderful analogy to use is that of the ‘knock-out punch.’ Early treatment with a high dose of effective medication can knock out a headache, rather than make the poor child go through 10 rounds of punishment.

Before the advent of triptan drugs, it was standard practice to prescribe combination drugs in an attempt to put the migraineurs to bed and sleep off the headache. Drugs such as Midrin, Fioriset, and Esgic have gone out of favor because of their sedative effect and potential for overuse.27,28 For these reasons, they should not be part of the armamentarium for young people.

Headache treatment changed dramatically in 1993 with the introduction of the triptan drugs. Migraines could be treated with drugs that attacked the physiology directly and could get patients back to work or school quickly. Choice of triptan is based upon a combination of factors. In general, injections and nasal sprays work faster and bypass the gut, whereas pills and melts require the co-operation of the patient s gastrointestinal (GI) tract. Also, in general, shots and nasal sprays may have more side effects, but can be relied on to do the same thing every time, whereas variability of absorption through the GI tract makes this route troublesome for some patients. In the US, 80% of the triptans sold are pills. Reluctance to use parenteral forms continues to dominate the US market. Since treating headache early is the best predictor of success, patients need to have permission to go straight to a triptan if their headache is bad. The pediatric practitioner must work closely with the school nurse to give children permission to take their triptans at first twinge. Splitting prescriptions to allow doses in school will give childhood migraineurs a chance to abort their headaches before getting home from school.

Triptan Studies in Childhood
Triptans have been extensively studied in childhood and in adolescents. Although efficacy rates were very high, few randomly controlled, doubleblind, placebo studies have shown benefit over placebo, due primarily to a very high placebo rate.29 33 Reasons for this high rate may be traced to problems in study design. Since children did not take their medicine or placebo until they got home from school, many of the headaches were resolving by the time drug or placebo was given. Another explanation for the high placebo rate is related to children s aim to please. Further, it is unclear whether adult consent allowed the children to understand the nature of a scientific experiment and recognize that non-response to placebo is just as important as response to drug. Future studies must account for these factors, since these safe drugs can offer a lot of help to youngsters.34

Migraine Prevention Strategies
Some believe that anyone can get a migraine if provoked, and migraineurs have a lower threshold than non-migraineurs. Potential triggers to avoid include hunger, stress, change in sleep patterns, and certain foods containing sulfites and MSG. Migraineurs are therefore encouraged to eat regularly, sleep regularly, and avoid foods that may trigger headache for them. Stress reduction, good eating habits, and smoking cessation are encouraged for all patients, regardless of migraine status.35 The decision to use prophylactic drugs for a migraine headache patient should be based on severity and frequency of attacks after prescribing a triptan. Days of missed school in an average month are an easy measure to follow. However, this measure may underestimate the impact of migraine. It is better to ascertain how many days a month the youngster is not functioning at peak capacity due to headaches. This can be measured indirectly by grade performance. Since success of prophylactic treatment is considered a 50% drop in frequency, the drugs we use for this purpose are not that good.36 Choice of drug, therefore, should be based upon what else is wrong with the patient. This comorbidity can help choose some drugs and avoid others. For example, beta-blockers exacerbate depression, asthma, and exercise intolerance, and so should not be used for the depressed, asthmatic patient or athlete.37 Topiramate is a good choice for an obese person,38 while cyproheptadine39 or a tricyclic antidepressant40 would help with weight gain. Valproate, Gabapentin, and Topiramate are anticonvulsants, so they could help a patient with migraine and epilepsy.41 Valproate is helpful in conduct disorder, so it could help a person with violent tendencies.42 Newer antidepressants such as Venflexamine43 may help alleviate anxiety as well as depression. As is the case with the triptans, there are few US Food and Drug Administration (FDA) approvals for use of these drugs in children and adolescents.44 Non-prescription medicinals have been used as well. Feverfew, magnesium, co-enzyme Q-10, and riboflavin may have a role in migraine prophylaxis.45 Biofeedback relaxation, hypnosis, and cognitive therapy work well for youngsters motivated to practice on a daily basis.46 These modalities work best with motivated youngsters, since these non-medicinal techniques require practice and vigilance.

Summary
The diagnosis of migraine in childhood is pretty straightforward. Autonomic symptoms, acute intermittent headache, a need to rest when headache is severe, and a strong family history, along with a benign exam, is all that is necessary for the diagnosis. Pointing out that there is no brain tumor during history taking, physical examination, and discussion will alleviate much of the heightened concern often not expressed during the visit. Treatment plans should stress normalcy and encourage healthy eating and sleep, exercise, and life stress modification. Acute treatment should stress early intervention with higher doses of oral pain medications, and use of triptans. Migraine prevention drugs should be saved for patients with measurable disability. Choice of drug is based upon comorbidities and side-effect profiles. Alternatives to medications work well for the motivated. Future drug studies in the field of pediatric headache should account for differences between children and adults in their study design to help reduce placebo rate in order that true efficacy can be demonstrated. It is my hope that obtaining pediatric indications for triptans will increase use of these valuable helpful medicines for the young headache sufferer.

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