High Frequency Episodic Migraine

Case Study Part 1

Episodic MigraineJT is a 30-year-old white female who presents complaining of frequent headaches. She describes her headaches as coming on without warning and as throbbing in nature, and she mainly feels them in her nasal region of her forehead, like a "pounding in her sinuses," lasting anywhere from 5-10 hours at a time. She has felt nauseous during most of these episodes and has vomited on several occasions due to the severity of the pain. She has an 18-month-old daughter and states that the headaches seem to come on more frequently when she is stressed caring for her child. She has no significant past medical history aside from a weight gain of 50 pounds during her pregnancy. She is not taking any medications. Her vital signs are within normal range, and her BMI calculates to 31 kg/m2.

Challenge Question 1

Which of the symptoms described by the patient align with diagnostic criteria established by the International Headache Society (IHS) for migraine without aura?

The IHS criteria or International Classification of Headache Disorders (ICHD) criteria have standardized the clinical definition of migraine. They define migraine as being with aura or without aura. There needs to be at least five lifetime attacks of migraine fulfilling these criteria without evidence of underlying disease causing the headaches. The headache lasts 4-72 hours and is characterized by two of the following four: moderate-to-severe intensity, throbbing, unilateral, and the headache is worse with activity. In addition, there needs to be nausea and/or vomiting, or both photophobia and phonophobia.

The symptoms and characteristics of the type of headache this patient is experiencing is most suggestive of migraine without aura. The headaches have a unilateral location, are pulsating in quality, last between 4 to 72 hours, and several episodes have been accompanied by nausea, all criteria fitting this diagnosis. Other criteria associated with migraine without aura include moderate or severe pain intensity, aggravation by or causing avoidance of routine physical activity, and photophobia or phonophobia. She has no symptoms suggestive of fully reversible aura and has noted no warning signs that a headache attack is imminent.1

Unlike migraine, tension-type headache is shorter in duration, and is characterized by a bilateral location, a non-pulsating, pressing or tightening quality, mild-to-moderate intensity, and not aggravated by physical activity. Nausea/vomiting and photophobia/phonophobia are not associated with tension-type headache.1

It is not unusual for migraine to be misdiagnosed as sinus headache. However, sinus headache symptoms include more than just pain in the region of the facial sinuses. Along with facial pain and pressure, a true sinus headache is characterized by nasal and sinus congestion along with headache and is usually secondary to a viral or bacterial sinus infection characterized by thick, discolored nasal discharge, diminished (or no) ability to smell, facial pain or pressure, and usually an accompanying fever.2


  1. Headache Classification Committee of the International Headache Society. The international classification of headache disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9):629-808.
  2. Hutchinson S. Sinus headaches. Available at: https://americanmigrainefoundation.org/understanding-migraine/sinus-headaches/.

Case Study Part 2

Upon further questioning, JT states that these headaches have been occurring for the past six months, and their frequency and severity is increasing. She states she has had 10 to 12 episodes alone in each of the past two months. She often feels too impaired by her headache episodes to properly care for her child because she has to lie down and remain immobile until they pass. She is currently a stay-at-home parent. She had hoped to return to full-time work once her child reached six months old, but she states that she never knows when a headache will take her "out of action," and she was fired from two recent part-time jobs because she was told she called out of scheduled work days too often because of her headache episodes.

Challenge Question 2

Considering her original presentation and this additional information, what type of migraine is this patient now experiencing?

Migraine is typically defined as episodic or chronic. Based on the information given, the patient is having episodic migraine, which in terms of frequency is characterized by headaches that occur on fewer than 15 days per month compared to chronic migraine which includes headache occurring on 15 or more days of the month.1 In addition to the signs and symptoms of episodic migraine, the patient is noted to have additional particular clinical factors for episodic migraine. Data have shown that female gender, white race, age younger than 50 years, and obesity are all associated higher odds of episodic migraine.2

However, the "border zone" between chronic and episodic migraine can often be murky. Patients with a higher frequency of episodic migraine may share similar headache-related disability and comorbidities with those who have been diagnosed with chronic migraine.3 High-frequency episodic migraine (HFEM) is now defined as headache experienced 10 to 14 days per months, vs low-frequency episodic migraine (LEFM) with 1 to 9 headache days monthly.3,4 Previous research has determined that that patients with HFEM suffered substantial consequences beyond the associated symptoms. Patients with HFEM were less likely to be employed full-time and were more likely to be occupationally disabled than those with LFEM, and as headache frequency increased, so did diagnoses of anxiety, depression, and other psychiatric comorbidities.3

A recent analysis of 1,109 patients by Torres-Ferrús, et al., found that there were three times more clinical differences between patients with LFEM and HFEM than there were between those with HFEM and chronic migraine. The migraine attack characteristics in patients with HFEM had more in common with chronic migraine than with LFEM, and the levels of physical and emotional disability were similar in patients with HFEM and those with chronic migraine.4


  1. Headache Classification Committee of the International Headache Society. The international classification of headache disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9):629-808.
  2. Peterlin BE, Rosso AL, Rosenger JR, et al. Episodic migraine and obesity and the influence of age, race, and sex. Neurology. 2013; 81(15):1314-1321.
  3. Montefiore Medical Center. "Border zone" between episodic and chronic migraine explored in research by Montefiore Headache Center. Available at: www.montefiore.org/body.cfm?id=1738&action=detail&ref=1061.
  4. Torres-Ferrús M, Quintana M, Fernandez-Morales J, et al. When does chronic migraine strike? A clinical comparison of migraine according to the headache days suffered per month. Cephalgia. 2017;37(2):104-113.

Case Study Part 3

Because of the severity and frequency of her migraine episodes, JT was started on sumatriptan 50 mg for acute episodes, increased one month later to 100 mg as she was not experiencing relief with the mid-range dose. She also initiated preventive therapy with oral topiramate, titrated to 50 mg twice daily.

On her follow-up visit, JT reports improvement in her headaches with a 50% reduction, but has been having significant issues with fatigue and a tingling sensation in her hands since starting on preventive medication. She requests a change in treatment and had heard that onabotulinumtoxinA could be an option for prevention as well as some new injection she recently heard about on the news that would be monthly.

Challenge Question 3

Which of the following would you now recommend for JT?

The excessive fatigue and paresthesia is most likely a side effect of the topiramate, so changing to a different preventive is an important option for JT. Lowering the dose can lessen side effects but could also lessen the benefit of topiramate. OnabotulimumtoxinA has been FDA-approved to prevent headaches in adults with chronic migraine who have 15 or more days each month with headache lasting 4 or more hours each day. JT has decided not to pursue this option now due to the amount of injection time this may require. The new injection JT had heard about was most likely the new category of CGRP (calcitonin gene-related peptide) antibodies that are being developed for prevention of frequent episodic and chronic migraine. However, you explain to JT that it is not available outside of clinical trials. There are four pharmaceutical companies working on this category of preventive medication and hopefully, CGRP monoclonal antibodies will be FDA-approved and available as early as 2018. She asks for more information about CGRP. You explain to her the CGRP is a neuro-inflammatory peptide which is released from nerve endings during a migraine like the nerve endings in her facial and forehead area. Research has shown that CGRP is a key player in migraine attacks and that by “neutralizing” it by blocking its activity it can prevent migraine. Data from the clinical trials indicate that this medication is safe and may work faster and better than all current preventive treatments.

The American Academy of Neurology and the American Headache Society have issued joint evidence-based guidelines for the prevention of episodic migraine in adults. These are summarized in Table 1.

She denies depression and does not want to go on an antidepressant. After discussion of potential side effects of the various medications, the decision is for JT to switch preventive medication to divalproex sodium. She will initially take 250 mg twice per day.

A follow-up appointment was made. A reduction in headache frequency and severity by at least 50% was the goal. Her sumatriptan 100 mg for acute episodes was refilled. If she is unable to tolerate the new preventive medication or if it is ineffective, then onabotulinumtoxinA may be an option for her. The CGRP category of preventive medication could also be a future treatment option for JT once FDA-approved and available in the US.

Multiple agents targeting CGRP are currently undergoing investigation for use in preventive therapy of migraine. These drugs attack the vasodilator CGRP but without causing vasoconstriction.1 Several monoclonal antibodies (mAbs) against CGRP have been studied in clinical trials. Antibodies that specifically target the CGRP ligand include fremanezumab, eptinezumab, and galcanezumab. Another anti-CGRP agent, erenumab, acts somewhat differently by targeting the CGRP receptor.1,2

Numerous Phase 1, 2, and 3 trials have demonstrated good safety and tolerability of the drugs and efficacy in migraine prevention, especially in high-frequent episodic and chronic forms of migraine.2 All four of these anti-CGRP mAbs have been found to demonstrate comparable efficacy that does not appear to differ substantially from currently available treatments for migraine. They have the potential to significantly improve adherence to therapy, tolerability, and safety in migraine prevention.2

Close continued follow-up of JT and patients like her is critical to achieving lessening of the burden of migraine. Although we cannot cure migraine, moving a patient from chronic migraine to an infrequent episodic migraine pattern is achievable for many migraine patients. With emerging novel agents like CGRP monoclonal antibodies, that goal may now be achievable for many who now struggle with oral preventive medications because of side effects or ineffectiveness.


  1. Bigal ME, Dodick DW, Rapoport AM, et al. safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine: A multicentre, randomised, double-blind, placebo-controlled, phase 2b study. Lancet. 2015;14(11):1081-1090.
  2. Mitsikostas DD, Reuter U. Calcitonin gene-related peptide monoclonal antibodies for migraine prevention: comparisons across randomized controlled studies. Curr Opin Neurol. 2017 Feb 24. doi: 10.1097/WCO.0000000000000438. [Epub ahead of print].