Headache 2010 the Author Journal compilation 2010 American Headache Society

ISSN 0017-8748 doi: 10.1111/j.1526-4610.2009.01600.x Published by Wiley Periodicals, Inc.

Resident and Fellow Section

Morris Levin, MD, Section Editor Section of Neurology Dartmouth Hitchcock Medical Center, Lebanon, NH

TEACHING CASE: MENOPAUSAL MIGRAINE Matthew S. Robbins, MD; Sara C. Crystal, MD; Brian M. Grosberg, MD Fellows in Headache Medicine (M.S. Robbins and S.C. Crystal) and Fellowship Program Director (B.M. Grosberg), The Monteore Headache Center, Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA CASE PRESENTATION A 46-year-old right-handed woman presented to the Monteore Headache Center with a history of episodic headaches since the age of 25. Her pain can be parietal, frontal, orbital, or holocranial; the pain can be bilateral or unilateral, switching sides between attacks, and described as throbbing, achy, dull, or pressure-like. The severity is graded anywhere between a 3 to a 10/10, and attacks typically last for 24 hours. Her headache frequency had been 1-2 attacks per month up until a few months ago, when the attack frequency escalated to 19 days of headache monthly. Associated symptoms include nausea, photophobia, phonophobia, and poor appetite. She also has discomfort from wearing contact lenses during her attacks. Any form of physical activity exacerbates her pain and she seeks relief by lying down in a dark, quiet room. Premonitory symptoms include sluggishness and vague neck discomfort. She has experienced a visual aura with approximately 25% of her attacks, characterized by seeing an ovoid area of ashing lights in the upper left hemield, which evolves to a zig-zag and wavy-lined pattern, expand338

ing over the central part of her visual eld, lasting for 10-20 minutes and then resolving. After a 10- to 20-minute pause, a typical headache would ensue. She has had visual aura in isolation 5 times in her life. Triggers include red wine, caffeine, ashing lights, and sleep deprivation. With approximately half of her menstrual cycles, she would have an attack on the day or 2 prior to her menses. Previous preventive medications only include a 2-month trial of riboavin 100 mg daily. Ibuprofen had worked effectively in the past, leading to pain freedom within 2 hours; however, the effect has waned and it no longer provides any signicant benet. Past medical history includes temporomandibular dysfunction and bruxism, for which she wears a night guard, and childhood asthma, which resolved. She is not depressed or anxious. Her mother has a history of multiple sclerosis and migraine without aura that abated with menopause. Menarche occurred at 10.5 years of age, and her menses had been quite regular until 6 months before presentation, when they became unpredictable, occurring from 3-week to 2-month intervals (Fig.). Although she had mild irritability and anxiety in the 3 days prior to her menses in the past, these symptoms have become much more prominent, and now encompass signicant insomnia and mood swings as well. She has also started to experience occasional hot ashes. She was headache-free during her 3 uncomplicated pregnancies. Her headaches have caused her to miss no days of work, but she feels much less productive than in months or years past. She works as an internist. She

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Figure.Lifetime occurrence of headaches.

lives with her husband and her 3 children. She drinks 1 glass of red wine weekly, and does not smoke or use illicit drugs. She exercises regularly. Her current medications include ibuprofen 800 mg 1-2 times daily as needed, calcium 500 mg twice daily, and riboavin 100 mg daily. She has no known drug allergies. General physical and neurological examinations were normal. Recent noncontrast brain MRI and blood tests, including serum chemistry, liver function tests, complete blood count, sedimentation rate, C-reactive protein, Lyme titer, and anti-nuclear antibody were all within normal limits.

EXPERT COMMENTARY Susan Hutchinson, MD Director, Orange County Migraine & Headache Center, Irvine, CA, USA Associate Clinical Professor, Department of Family Medicine, UC Irvine Medical Center, Irvine, CA, USA This case is a good example of perimenopausal exacerbation of migraine. This female patient had a 19-year history of episodic migraine with common migraine triggers including menses for approximately half her menstrual cycles. Prior to her recent escalation to 19 days of headache monthly, her headaches met the criteria for migraine with aura (25% of her attacks) and migraine without aura (75% of her attacks).1

Although there is a menstrual association with approximately half her menstrual cycles, she does not meet the criteria for menstrual migraine. Menstrual migraine, by denition, is migraine without aura that occurs with at least 66% of menstrual cycles.1 Her headache pattern has now transformed to >15 days/month for a few months; if this pattern has been present for at least 3 months, she now meets the criteria for chronic daily headache (CDH) with subtype transformed or chronic migraine. In her case, there is no evidence of medication overuse headache. The cause for her recent exacerbation can be explained by the recent 6-month irregularity of her menses. In a traditional 28-day cycle, there are fairly predictable changes in estradiol and progesterone levels. The drop in estradiol at the end of the luteal phase (just prior to menses) is a common trigger for migraine in women migraineurs. With the advent of perimenopause, estradiol and progesterone levels uctuate widely and are no longer predictable. Perimenopause is commonly referred to as the change before the change. The age of onset varies but typically begins in the late 40s and lasts approximately 4 years until menopause. Menopause is dened as no spontaneous menses for 1 full year and is supported by a high follicle stimulating hormone (FSH) level and a low estradiol level. In our case this patient has had an appropriate work-up for a secondary headache including a normal

340 recent brain MRI. No additional tests are felt necessary at this time. An FSH and estradiol level could be done but are not necessary. It is important, however, to determine if she is using contraception. There is no mention of this in the case history. Many women assume they can no longer get pregnant when their menses become irregular; it should be emphasized to this patient that she can still ovulate and get pregnant so contraception is critical. How should this patient be treated? First, she deserves an explanation of why her headaches are so out of control. Second, she should be reassured that 2/3 of women with migraine will experience a marked improvement or in some cases, a complete cessation of their migraines once they are completely menopausal if they enter menopause spontaneously.2 A review of her history is reassuring in that her mother had migraine without aura that abated with menopause. Offering her a triptan for acute migraine relief would make sense since she is no longer getting signicant relief from her ibuprofen. More importantly, she needs a daily preventive regimen and ideally, one that will offer relief for her vasomotor symptoms including her insomnia, hot ashes, and mood swings. Preventive options include topiramate, venlafaxine, gabapentin, uoxetine, and herbal options. The potential sedative side effect of topiramate can be useful for perimenopausal-related insomnia; additionally, the reassurance of no weight-gain can make this an ideal preventive agent for many perimenopausal women for migraine prevention. Venlafaxine, a combined serotonin and norepinephrine-reuptake inhibitor, SNRI, was shown to reduce hot ashes by 37% from baseline for the 37.5 mg dose and a 60% reduction for both the 75 and 150 mg daily dosages. The effect on hot ashes was relatively rapid, with a full effect seen within 1-2 weeks.3 Fluoxetine has shown efcacy in the reduction of hot ashes and may help address the mood swings this patient is experiencing.4 Gabapentin given in a dose of 900 mg/day for 12 weeks was shown to reduce hot ashes in a randomized, controlled clinical trial.5 If this patient declines a prescription preventive, a modication of her herbal preventive regimen can be recommended. She is currently taking riboavin 100 mg a day; this

February 2010 could be increased to a 400 mg total daily dose; magnesium could be added at 400 mg total daily dose; and butterbur 150 mg total daily dose could be considered. The use of estrogen for this patient would be highly controversial given her history of migraine with aura. Utilization of non-hormonal treatment in her case would be a more appropriate rst-line treatment. Any decisions regarding estrogen would be best done in conjunction with her treating gynecologist. This case is an excellent example showing the strong association of hormonal uctuation and migraine exacerbation. Times of hormonal uctuation include menses, pregnancy, post-partum, and perimenopause. Being aware of the hormonal status of our women migraine patients is critical to our evaluation and treatment of these women in our practice.

REFERENCES
1. Headache Classication Committee. The international classication of headache disorders, 2nd edition. Cephalalgia. 2004;24:1-160. 2. Neri I, Granella F, Nappi R, et al. Characteristics of headache at menopause: A clinico-epidemiologic study. Maturitas. 1993;17:31-37. 3. Loprinzi CL, Kugler JW, Sloan JA, et al. Venlafaxine in management of hot ashes in survivors of breast cancer: A randomized controlled trial. Lancet. 2000;356:2059-2063. 4. Loprinzi CL, Sloan JA, Perez EA, et al. Phase III evaluation of uoxetine for treatment of hot ashes. J Clin Oncol. 2002;20:1578-1583. 5. Guttoso T Jr, Kurlan R, McDermott MP, et al. Gabapentins effects on hot ashes in postmenopausal women: A randomized controlled trial. Obstet Gynecol. 2003;101:337-345.

QUESTIONS FOR DISCUSSION

1 How are perimenopause and menopause dened and diagnosed? 2 Why might migraine with aura be less affected by hormonal changes? 3 What is the difference between headaches associated with PMS (premenstrual syndrome) and menstrually related migraine (MRM)?

Headache 4 What are the risks of prescribing estrogen to a patient like the one described? 5 What percentage of migraine sufferers improve during pregnancy? After menopause has stabilized?

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This case presentation and discussion meets the ACGME requirements for residency training in the following core competency areas: Patient Care, Medical Knowledge, Practice Based Learning, and Improvement and Systems Based Practice.