48-year-old woman with migraine with aura and menstrual ‘sinus’ headaches Presented by: Anne MacGregor Barts Sexual Health Centre, St. Bartholomew’s Hospital, London, UK CLINICAL CASE

IDENTIFICATION 48-year-old woman with migraine with aura and menstrual ‘sinus’ headaches A common misdiagnosis of menstrual migraine without aura in a woman with migraine with aura

CASE PRESENTATION (I) SR is a 48-year-old magazine editor who has disabling attacks of migraine with aura and menstrual ‘sinus’ headaches Attack frequency –Migraine with aura: every 4-6 weeks –‘Sinus’ headaches: with menstruation

CASE PRESENTATION (II) Description of migraine with aura –Fortification spectra lasting minutes –Unilateral headache associated with photophobia and nausea lasting one day Description of ‘sinus’ menstrual headaches –Onset of sinus congestion followed by frontal headache associated with photophobia and nausea lasting two to three days –No purulent nasal discharge; afebrile

CASE PRESENTATION (III) Periods irregular and unpredictable 5/22-35 days –Menstrual headaches disabling –Occasional cramps on day 1

CASE PRESENTATION (IV) Treatment for migraine –Frovatriptan 2.5 mg at onset of aura No more effective than ibuprofen Treatment for ‘sinus’ headaches –Nasal decongestant No longer effective –Ibuprofen Partly effective but only if taken early

PAST CLINICAL HISTORY (I) Headaches –First attack of migraine with aura aged 12 –‘Sinus’ headaches that resolved in her 20s –‘Sinus’ headaches returned 6 years ago associated with menstrual but less of a problem until periods became unpredictable

PAST CLINICAL HISTORY (II) Takes the progestogen-only pill –Combined hormonal contraceptives contraindicated because of migraine with aura Three pregnancies –Migraine continued unchanged

PAST CLINICAL HISTORY (III) Depression and anxiety –Rx sertraline Otherwise healthy Systems review normal

FAMILY HISTORY Parents –Mother well – no medical complaints –Father died from prostate cancer – Hx migraine with aura Siblings –Younger brother – migraine with aura –Older sister – no medical complaints

PHYSICAL EXAMINATION On examination she looks in good health Physical examination and neurological assessments were unremarkable BP 120/75 mmHg BMI 26.7 kg/m 2

DIAGNOSTIC PROCEDURES None indicated –No atypical features in the history –Physical and neurological examinations normal

DIAGNOSIS (I) Does she have migraine with aura? –SR describes fully reversible visual fortification spectra followed by headache associated with nausea, photophobia and disability –She is free of symptoms between attacks –Normal physical and neurological examination This suggests a diagnosis of migraine with aura Cephalalgia 2013;33:

DIAGNOSIS (II) What are the ‘sinus’ headaches? –SR describes episodic headache associated with nausea, photophobia and disability with complete freedom from symptoms between attacks –Associated ‘sinus’ congestion but no nasal discharge This suggests a diagnosis of migraine without aura

DIAGNOSIS (III) Attacks of migraine without aura occur regularly with menstruation She has attacks of migraine with aura at other times of the cycle This suggests a diagnosis of menstrually-related migraine without aura (Fig. 1) –Diary cards can confirm the diagnosis Cephalalgia 2013;33:

Figure 1: ICHD III: MENSTRUALLY-RELATED MIGRAINE A. Attacks, in a menstruating woman, fulfilling criteria for Migraine without aura and criterion B below B. Documented and prospectively recorded evidence over at least three consecutive cycles has confirmed that attacks occur on day 1 ± 2 (i.e. days -2 to +3) of menstruation in at least two out of three menstrual cycles, and additionally at other times of the cycle Notes: 1. For the purposes of ICHD-3 beta, menstruation is considered to be endometrial bleeding resulting from either the normal menstrual cycle or from the withdrawal of exogenous progestogens, as in the use of combined oral contraceptives or cyclical hormone replacement therapy. 2. The first day of menstruation is day 1 and the preceding day is day -1; there is no day 0 Cephalalgia 2013;33:

DIAGNOSIS (III) Diary shows (Fig. 2) –Migraine without aura starting on day 1 of menstruation; duration 3 days –Migraine with aura unrelated to menstruation; duration 1 day

Figure 2: THE PATIENT’S HEADACHE DIARY

TREATMENT (I) What is her current treatment and is she taking it optimally? –Migraine with aura SR takes frovatriptan at onset of aura; optimal time is onset of headache –Menstrual migraine Correct diagnosis of migraine and failed response to analgesics merits consideration of a triptan

TREATMENT (II) Are there any relevant non-hormonal triggers? Identification of non-hormonal triggers are important, even for women with pure menstrual migraine. This is importnat because most attacks are the result of several triggers building up over the cycle.

GeneticPredisposition/Prophylaxis threshold HORMONAL TRIGGER LACK OF FOOD DEHYDRATION MUSCULAR PAIN LACK OF SLEEP MacGregor EA. 1996;16:11-21 MacGregor EA. Cephalalgia 1996;16:11-21 Figure 3: TRIGGER THRESHOLD

TREATMENT (III) Would she benefit from daily prophylaxis? –Depends on attack frequency and response to acute treatment –For women who have frequent attacks throughout the month, it is worth considering a daily prophylactic treatment in addition to acute medication, particularly if the response to acute medication is poor

TREATMENT (IV) Treatment management –Symptomatic treatment: migraine with aura Recommend frovatriptan at onset of headache, not onset of aura –Symptomatic treatment: menstrual attacks Recommend frovatriptan at onset of headache, repeating for relapse of long-duration attacks –Diary records for three months –Consider non-hormonal triggers

FOLLOW-UP Review diary cards to confirm diagnosis of menstrually-related migraine (Fig. 4) Review efficacy of acute treatment and consider need for prophylaxis (Fig. 5)

Figure 4: ASSOCIATION BETWEEN MIGRAINE AND MENSTRUATION

Figure 5: ACUTE TREATMENT WITH FROVATRIPTAN

TREATMENT EVALUATION Diary shows that menstrual attacks respond to frovatriptan and that she treats symptoms as soon as headache starts and repeats for relapse Headache and associated symptoms of migraine with aura respond to frovatriptan taken at onset of headache

CLINICAL EVALUATION Diary confirms menstrual irregularity Bright sunlight and dehydration were identified as modifiable triggers for migraine with aura Daily prophylaxis is not indicated given her frequency of attacks and response to acute treatment

REMARKS (I) Menstrual irregularity is common during the perimenopause and can be a challenge for effective management of menstrual migraine Migraine without aura commonly misdiagnoses as ‘sinus’ headache MacGregor EA. Curr Pain Headache Rep. 2009;13: ; Schreiber CP, et al. Arch Intern Med 2004;164: ; MacGregor EA, et al. Neurology 2006;67:

REMARKS (II) Early treatment improves efficacy and reduces pain and functional disability Triptans should be taken at the onset of migraine headache, not onset of migraine aura Comorbid depression and anxiety can be treated with an SSRI without significant risk of serotonin syndrome Cady R, et al. Curr Med Res Opin 2004;20: ; Bates D, et al. Neurology. 1994;44: ; Olesen J, et al. Eur J Neurol. 2004;11:671-7; Dowson A. Eur Neurol. 1996;36(Suppl. 2):28-31; Gilman PK. Headache 2010;50:

REMARKS (III) Frovatriptan is effective for menstrual and non- menstrual migraine Long-duration attacks, such as menstrual migraine, need long-duration treatment, such as frovatriptan Diary cards are essential to confirm the diagnosis and assess the effects of treatment Cortelli P, et al. Neurol Sci 32 Suppl 1:S95-98; Allais G, et al. Neurol Sci 2011;32 Suppl 1:S99-104; Sarchielli P, et al. J Headache Pain 2012;13(Suppl2):S31-70; Geraud G, et alHeadache 2003;43:376-88; Evers S, et al. Eur J Neurol 2009;16:968-81; Bendtsen L, et al. J Headache Pain ; Suppl1:S1-29.