The chief complaint read, “Please don’t let her suffer like I did.”
On a typical clinic day, I entered the examination room to find a 10 year old girl, accompanied by her mother and grandmother, who had been referred for headache.
The mother, an attorney for a small local firm, began the patient’s history with her own lifelong experiences with headache and the anguished plea that we help to make sure her daughter does not have to suffer the same fate.
As a toddler, the mother had episodes of unexplained vomiting. Approximately once a month, she would begin to throw up in the early morning hours and vomit repeatedly until she became dehydrated. The grandmother painfully recalled countless visits to the emergency departments, and the use of intravenous fluids and ineffective medicines for nausea and -vomiting. No cause was ever determined.
By the time she was in elementary school these cycles of vomiting had ceased, but she began to have dizzy headaches lasting from several hours up to a day, which caused her to miss school once or twice a month. Repeated medical evaluations, including computerized tomography scans and electroencephalograms, were normal and the cause was attributed to psychologic factors -stemming from the death of her grandfather.
During her teenage years and throughout college, two- or three-times per month, the mother would experience excruciating -headaches with heralding hand and facial numbness. She recalls being dopey all the time because she was repeatedly prescribed aspirin/butalbital preparations and took two doses, as instructed, every 4 h during an episode. Each menstrual cycle was associated with an intense series of headaches for which she was told to double-up on the doses.
Approximately 2 months ago, the mother found the website www.achenet.org on the internet and read the various patient information sections from the American Council for Headache Education Citation[101]. She found a local physician who was comfortable in treating headaches. She was diagnosed with migraine with aura, started on a treatment program and now she feels like she has her life back.
Her 7 year old daughter has episodes that occur once a week during which she feels unsteady and vertiginous for approximately 20 min and then has several hour-long frontal, pounding, nauseating headaches, which are relieved by sleep.
The daughter’s physical and neurologic examinations were perfectly normal. She has basilar-type migraine. Her mother evolved through cyclic vomiting syndrome to basilar-type migraine to migraine with aura (chiro-oral aura) and is now well controlled with daily topiramate and nasal sumatriptan, as required, coupled with some lifestyle changes including regular sleep schedules, regular aerobic -exercise, regular meals and moderation of caffeine intake.
Migraine headaches are very common and, unfortunately, often underdiagnosed. Three populations, adult women, children and adolescents and the elderly, are among those most frequently unrecognized. The prevalence of migraine evolves through childhood from 3 to 5% of young school children up to 8–15% of adolescents. The 1-year prevalence of migraine in adults is 13% (17% in women, 6% in men; 2.9:1) Citation[1]. More than half of patients with migraine go undiagnosed or are -misidentified Citation[2].
First step is accurate diagnosis
The standard medical model of history and physical examination is usually sufficient to establish a diagnosis of migraine. For a subset of patients with unusual or atypical features, neurodiagnostics with laboratory testing, magnetic resonance imaging and electroencephalography may be indicated. For most patients, history and a physical examination are sufficient to establish the correct diagnosis.
The International Headache Society (IHS) has recently published the new classification system for headaches and generated updated diagnostic criteria for migraine headache Citation[102]. The 2004 IHS criteria for headache disorders for migraine without aura are:
| • | 1. More than five attacks fulfilling the features below: | ||||
| • | 2. Headache attack lasting 4–72 h (1–72 h for children) | ||||
| • | 3. Headache has at least two of the following four features: | ||||
- Unilateral location (may be bilateral frontal/temporal in children <15 years of age)
- Pulsating quality
- Moderate-to-severe intensity
- Aggravated by routine physical activities
| • | 4. At least one of the following accompanies headache: | ||||
- Nausea and/or vomiting
- Photophobia and phonophobia (which may be inferred by behavioral responses in children)
These new criteria have adopted more developmentally sensitive features, enhancing their utility in childhood. Children typically have shorter headaches than their adult counterparts and are often unable to describe the associated symptoms of photophobia, phonophobia, nausea and aggravation by activity. In the absence of these historical terms, observation of the child’s behavior during an attack may imply or infer their presence by the report that the child withdraws from play to a dark, quiet room.
It is imperative for clinicians caring for children, adolescents and young adults to become aware of the migraine spectrum, diversity of symptoms that may be associated with the migraine syndromes and evolution of headache patterns through the -lifecycle. The new classification system has included disorders such as cyclic vomiting, and abdominal migraine and clinical entities peculiar to children Citation[103]. The 2004 IHS criteria for cyclical vomiting is described as recurrent episodic attacks, usually stere-otypical in the individual patient, of vomiting and intense nausea. Attacks are associated with pallor and lethargy. There is complete resolution of symptoms between attacks. The -diagnostic criteria are:
| • | 1. At least five attacks fulfilling criteria 2 and 3 | ||||
| • | 2. Episodic attacks, stereotypical in the individual patient, of intense nausea and vomiting lasting 1–5 days | ||||
| • | 3. Vomiting during attacks occurs at least five-times/h for at least 1 h | ||||
| • | 4. Symptom free between attacks | ||||
| • | 5. Not attributed to another disorder. History and physical examination do not show signs of gastrointestinal disease | ||||
The key historical feature of the migraine spectrum is the episodic nature, with attacks lasting from hours up to a few days, separated by symptom-free intervals.
In the case history reported above, the grandmother beautifully described cycles of pernicious vomiting which we now recognize as cyclic vomiting syndrome (CVS). CVS is second only to reflux as a common cause of recurrent vomiting in children. This curious clinical entity is one of the most disabling forms of migraine. When the child begins an episode, often early in the morning hours, the whole family is disrupted until the cycle concludes or is successfully aborted.
Treatment of CVS follows the migraine paradigm with efforts directed to prevent the episodes with agents such as cyproheptadine, amitriptyline or topiramate and aggressive intervention at the onset of attacks with hydration, sedation (e.g., lorazepam), analgesics (e.g., ibuprofen), antiemetics (e.g., ondansetron) and triptans (e.g., subcutaneous sumatriptan).
A related condition recently added to the migraine spectrum is abdominal migraine. This is a troublesome entity and the description is remarkably vague. The 2004 Internation Classification of Headache Disorders (ICHD) criteria for abdominal migraine is described as an idiopathic recurrent disorder seen mainly in children and characterized by episodic midline abdominal pain manifesting in attacks lasting 1–72 h with normality between episodes. The pain is of moderate-to-severe intensity and associated with vasomotor symptoms, nausea and vomiting. The diagnostic criteria are:
| • | 1. At least five attacks fulfilling criteria 2–4 | ||||
| • | 2. Attacks of abdominal pain lasting 1–72 h | ||||
| • | 3. Abdominal pain has all of the following characteristics: | ||||
- Midline location, periumbilical or poorly localized
- Dull or just sore quality
- Moderate or severe intensity
| • | 4. During abdominal pain, at least two of the following: | ||||
- Anorexia
- Nausea
- Vomiting
- Pallor
| • | 5. Not attributed to another disorder. History and physical examination do not show signs of gastrointestinal or renal disease or such disease has been ruled out by -appropriate -investigations. | ||||
Ironically, headache is not part of the clinical criteria. I recently showed the new ICHD criteria to our pediatric gastroenterology division and they, in unison, gleefully said this was recurrent abdominal pain (RAP). There is, apparently, a huge population of children and adolescents with ill-defined, recurrent abdominal pains collected in gastrointestinal clinics around the country. While I do not doubt that abdominal migraine exists as a clinical entity, the proportion of RAP that will fall into the spectrum of abdominal migraine is unknown (figure 1).
Pediatric neurology offices around the country should anticipate a flow of patients presenting with recurrent belly pain. Our office is already receiving calls and inquiries. Effort must be expended to better define this disorder and develop more sensitive diagnostic tools.
A host of new interventions are now available for both the acute treatment and prevention of migraine. The American Academy of Neurology has published practice parameters for the evaluation and management of migraine providing evidence-based guidelines for the acute and preventive treatment of children, adolescents and adults Citation[104]. These guidelines provide excellent resources for clinicians to become familiarized with the latest and most effective treatments for migraine across the span of ages.
Acute treatments with the triptans class of agents has revolutionized our treatment of migraine and greatly improved the quality of life of migraine sufferers reducing dependence upon sedating analgesic drugs (table 1).
On the near horizon are novel compounds such as calcitonin gene-related protein (CGRP) antagonists that may further advance the treatment options for patients with migraine and decrease dependence upon sedating agents.
The use of triptan agents in children and adolescents warrants special mention. None are currently approved by the US Food and Drug Administration. While safety data exists for several of the triptan agents, only sumatriptan nasal spray (5 and 20 mg) has controlled data demonstrating efficacy, but even this data has been challenged by the Food and Drug Administration which recently denied pediatric indication. In order to satisfy the mandate and demonstrate statistically significant results in clinical trials, innovative new study designs must be sought which take into consideration the unique features of pediatric migraine and high placebo responder rates found in pediatric trials.
Clearly, years of clinical experience from around the globe has proven a role for these agents in children and adolescents who fail to respond to simple analgesic agents. In our practice, we confidently use and prescribe the triptan agents for children with moderate-to-severe attacks of migraine down to 6 years of age. The nasal spray preparations (e.g., sumatriptan and zolmitriptan) and the oral disintegrating tablets (e.g., rizatriptan and zolmitriptan) have been the most acceptable and tolerable for our population of children. However, the managed care industry, in general, has failed to acknowledge good clinical judgment and has not been receptive to the use of triptans in the pediatric population.
For patients with frequent or disabling attacks of migraine, a wide variety of preventive regimens including antiepileptic drugs such as divalproex sodium and topiramate have shown efficacy. There is also a growing appreciation of the beneficial effects of lifestyle modifications (i.e., sleep hygiene, exercise, regular balanced diet and caffeine moderation). The American Headache Society has a patient information
Table 1. The triptan agents.
There is growing appreciation for the need to diagnose and treat migraine as soon as possible. We now understand that frequent, undertreated migraine attacks set the stage for the development of central and peripheral sensitization of pain circuitry and evolution of allodynia wherein seemingly innocuous influences become painful. We know that overuse of over-the-counter preparations (e.g., aspirin, acetaminophen and ibuprofen) actually facilitates the progression toward chronic daily headache. Furthermore, intriguing information suggests deposition of iron, perhaps from increased vascular permeability, within deep brain structures in patients with long standing migraine.
The Pediatric Headache section of the American Headache Society has begun an ambitious project to explore the natural history of migraines that begin during the childhood years with the hypothesis that early intervention will substantially reduce headache disability throughout the lifecycle. I predict that these types of longitudinal projects will confirm our instincts that early diagnosis and intervention will substantially reduce the burden of migraine and provide a response to the mother’s plea, “Please don’t let her suffer like I did.”
Conclusion
The future is bright for patients who suffer with migraine, but the key is early diagnosis and treatment in order to limit lifelong disability as suffered by the mother in the introductory case presentation. Primary care clinicians must become more aware of the migraine spectrum to permit early diagnosis and migraine-specific treatment. Knowledge of these up-to-the-minute options will aid the clinician to diagnose and develop an individually tailored treatment program for migraineurs of any age and hopefully help ease the suffering.
Table 1. The triptan agents.
References
- Lipton RB, Scher IA, Kolodner K et al. Migraine in the United States: epidemiology and patterns of health care use. Neurology 58, 885–894 (2002).
- Lipton RB, Stewart WF, Liberman JN. Neurology58(9 Suppl. 6), S21–S26 (2002).
Websites
- American Council for Headache Education www.achenet.org (Accessed April 2005)
- International Headache Society www.i-h-s.org (Accessed April 2005)
- Cyclic Vomiting Syndrome www.cvsaonline.org (Accessed April 2005)
- American Academy of Neurology www.aan.com (Accessed April 2005)