Clinical cases.

Clinical cases

Case: Ms. MC Speaker’s Notes
Please present the case to the participants.

Ms. MC: Profile 30-year-old female, nurse
Diagnosed with migraine without aura 3 years ago No other significant medical history Has been taking the same estroprogestative oral contraceptive (estroprogestative: levonorgestrel, 0.15 mg + ethinylestradiol, 0.03 mg for the last 7 years Speaker’s Notes

Ms. MC: History One-year history of migraine without aura attacks exclusively during menstruation Attacks are long lasting (4 days) Acute treatment with sumatriptan Immediate efficacy (pain-free within 3 hours) Relapse within 12 hours after initial intake each day Needs to take 8 triptan doses in 4 days to relieve pain Significant negative impact on quality of life Anxious anticipation of menstrual periods Speaker’s Notes

Discussion Questions based on the case presentation, what would you consider in your differential diagnosis? what further history would you like to know? what tests or examinations would you conduct? Speaker’s Notes Ask the questions shown on the slide to stimulate discussion.

Menstrual Migraine ~60% of female migraine sufferers have menstrual migraines Reduced estrogen at menstruation can trigger migraine Menstrual migraines may be more persistent, painful, and resistant to treatment than migraines that occur at other times ICHD criteria: Migraine without aura occurring between 2 days prior and 3 days after the onset of menses and in 2 of 3 menstrual cycles Some women experience migraine perimenstrually Headache diary should be used to record timing of menstrual migraines Speaker’s Notes A estimated 60% of female migraine sufferers have menstrual migraines (46% with “menstrually related migraine” and 14% with “pure menstrual migraine”). Reduced estrogen at menstruation can trigger migraine in many women May be more persistent, painful, and resistant to treatment than migraines that occur at other times ICHD criteria: Migraine without aura occurring between 2 days prior and 3 days after the onset of menses and in 2 of 3 menstrual cycles Some women experience migraine perimenstrually Headache diary should be used to record timing of menstrual migraines The drop in estrogen levels that occurs at menstruation can be a powerful trigger for migraine in many women. In patients with menstrual migraine, headaches are predictably timed to the menstrual cycle, although patients also frequently have headaches at other times. Reports from specialty clinics suggest menstrual migraine may be more persistent, painful, and resistant to treatment than migraines that occur at other times, but this finding has not been confirmed in population-based research. Menstrual migraine is not a separate diagnostic category; however, the International Classification of Headache Disorders (ICHD) has established criteria for use in clinical trials of menstrual migraine: migraine without aura occurring between 2 days prior and 3 days after the onset of menses (days −2 through +3) and in 2 of 3 (66%) menstrual cycles. Although menstrual migraine, by definition, is migraine without aura, women may experience migraine with aura perimenstrually. In clinical practice, it is important to assess the relationship between headache onset and menstruation. Timing should be corroborated with a headache diary or calendar; data from these sources are crucial for accurate diagnosis and subsequent treatment planning. Reference Menstrual migraine: breaking the cycle. Available at: Accessed 14 December, ICHD = International Classification of Headache Disorders Menstrual migraine: breaking the cycle. Available at: Accessed 14 December, 2014.

Estrogen Levels and Menstrual Migraine
Speaker’s Notes Levels of estrogen fall during the late luteal phase of the normal menstrual cycle and are at their low point a few days before and after the onset of menses. Estrogen decline is the primary trigger of menstrual migraine. A study of 38 women with menstrual migraine found that the cyclic decline in estrogen levels was inversely proportional to the prevalence of migraines, as shown in the graph on this slide. It has been hypothesized that as estrogen levels decline, there is a concurrent drop in levels of brain serotonin (5-hydroxytryptamine [5-HT]) or endorphin levels, which makes the patient more vulnerable and sensitive to pain. Other mechanisms that are unrelated to estrogen may also contribute to menstrual migraine. These include elevated prostaglandins (possibly due to endometrial prostaglandin production), decreased responsiveness to endogenous opioid activity (decreased opioid tonus), and a decline in circulating ionized magnesium levels. The exact mechanisms of menstrual migraine, however, are not fully understood. Reference Menstrual migraine: breaking the cycle. Available at: Accessed 14 December, 2014. Menstrual migraine: breaking the cycle. Available at: Accessed 14 December, 2014.

Discussion Question would you make any changes to therapy or conduct further investigations? Speaker’s Notes Ask the question shown on the slide to stimulate discussion.

Ms. MC: Further Tests/Examinations
In this clinical case there is no need for further tests. If desired, a diary could be filled to confirm the reality of pure menstrual migraine. Speaker’s Notes

what would be your diagnosis for this patient?
Discussion Question what would be your diagnosis for this patient? Speaker’s Notes Ask the question shown on the slide to stimulate discussion.

IHS Diagnostic Criteria for Menstrual Migraine
Attacks, in a menstruating woman, fulfilling criteria for migraine without aura Attacks occur exclusively on day 1+2 (i.e., days 2 to +3)1 of menstruation in at least two out of three menstrual cycles and at no other times in the cycle Speaker’s Notes This slide outlines the diagnostic criteria for menstrual migraine according to the International Headache Society. Reference Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9): Link to IHS Diagnosis of Menstrual Migraine 1The first day of menstruation is day 1 and the preceding day is -1; there is no day 0 IHS = International Headache Society Headache Classification Committee of the International Headache Society (IHS). Cephalalgia. 2013;33(9):

Ms. MC: Diagnosis This patient has pure menstrual migraine
Her attacks are difficult to treat She has recurrence of pain even with treatment with triptans

what treatment strategy would you recommend?
Discussion Question what treatment strategy would you recommend? Speaker’s Notes Ask the question shown on the slide to stimulate discussion.

Pharmacological Treatments for Menstrual Migraine
Acute Short-term Preventative Long-term Preventative NSAIDs Acetaminophen + Aspirin + caffeine Triptans NSAIDS Estrogen transdermal patches/gel Hormonal* Beta-blockers Calcium channel blockers Tricyclic antidepressants Anticonvulsants Speaker’s Notes This slide lists medications that can be used for acute migraine attacks and for prophylaxis (both short- and long-term). Reference Martin VT. Menstrual migraine: new approaches to diagnosis and treatment. Available at: _Menstrual_Martin.pdf. Accessed March 26, 2015. *Long duration oral contraceptives, gonadotropin-releasing hormone antagonists NSAID = non-steroidal anti-inflammatory drug Martin VT. Menstrual migraine: new approaches to diagnosis and treatment. Available at: Accessed March 26, 2015.

Ms. MC: Treatment Step 1: Acute Treatment Optimization
Determine if triptan is taken early enough in the attack (within 1 hour of onset while pain is of mild intensity) If not, try the same triptan, stressing the need to take it early in the attack If early treatment is ineffective, try a triptan + NSAID combination Alternatively, try a different triptan Evidence is weak, particularly for triptans with long half-lives NSAID = non-steroidal anti-inflammatory drug

Ms. MC: Treatment Step 2: Prevention of Menstrual Migraine Attacks
Sequential prevention by estradiol or triptan If menstrual cycle is regular and patient is adherent to therapy Continuous estroprogestative oral contraceptive or pure progestative oral contraceptive With the agreement of the patient’s gynecologist

Case: Mrs. LT Speaker’s Notes

Mr. LT: Profile 48-year-old female, executive secretary
Diagnosed with migraine without aura 20 years ago Mild generalized anxiety Non-active asthma Overweight (BMI = 26.4 kg/m2) Confirmed menopause since 1 year She has non-active asthma (asthma in childhood) Speaker’s Notes BMI = body mass index

Mr. LT: History 20-year history of migraine without aura attacks
Frequency of attacks is increasing Speaker’s Notes

Mrs. LT’s Headache Diary
Day/Week Mon Tues Wed Thurs Fri Sat Sun Week 1 Migraine Triptan Week 2 Week 3 Headache No therapy Week 4 Speaker’s Notes

Mr. LT: History Patient has been using a triptan for acute treatment
HIT-6 score = 58 HAD Anxiety score = 9 (mild anxiety) HAD Depression score = 3 (no depression) Very good quality of life without avoidance behavior Speaker’s Notes HAD = Hospital Anxiety and Depression

Tools to Assess Impact of Migraine
Test Comments MIDAS (Migraine Disability Assessment) 5-item tool Scores number of days of inactivity due to migraine in the past 3 months Headache Impact Test™-6 (HIT-6) Covers 6 categories Useful in clinical practice and research Headache Needs Assessment (HANA) 7-item self-administered tool Can help identify which patients require treatment Short Form 36® (SF-36®) 36 items covering physical and mental components of health Generic measuring tool to identify quality of life issues Speaker’s Notes This slide summarizes some of the tools available to assess the impact of migraine on patients’ lives. References Stewart WF, Lipton RB, Dowson AJ, Sawyer J. Development and testing of the Migraine Disability Assessment (MIDAS) Questionnaire to assess headache-related disability. Neurology. 2001;56(6 Suppl 1):S20-8. Kosinski M, Bayliss MS, Bjorner JB et al. A six-item short-form survey for measuring headache impact: the HIT-6. Qual Life Res. 2003;12(8): Cramer JA, Silberstein SD, Winner P. Development and validation of the Headache Needs Assessment (HANA) survey. Headache. 2001;41(4):402-9. Ware, JE Jr. SF-36® Health Survey Update. Available at: Accessed 03 December, 2014. Stewart WF et al. Neurology. 2001;56(6 Suppl 1):S20-8; Kosinski M et al. Qual Life Res. 2003;12(8):963-74; Cramer JA et al. Headache. 2001;41(4):402-9; Ware, JE Jr. Available at:

HIT – Headache Impact Test
Helps patients communicate the severity of their headache pain to their health care provider Helps to Determine impact of headaches on patient’s life Better communicate the information to the health care provider Track the patient’s headache history and response to therapy over time Speaker’s Notes Kosinski et al. developed a short form Headache Impact Test-6 (HIT6) to assess the impact of headaches that has broad content coverage but is brief, reliable and valid enough to use in screening and monitoring patients in clinical research and practice. HIT6 items were selected from an existing item pool of 54 items and from 35 items suggested by clinicians. The HIT6 was evaluated in an Internet based survey of headache sufferers (n = 1103) who were members of America Online (AOL). After 14 days, 540 participated in a follow up survey. HIT6 covers six content categories represented in widely used surveys of headache impact. Internal consistency, alternate forms, and test retest reliability estimates of HIT 6 were 0.89, 0.90, and 0.80, respectively. Individual patient score confidence intervals (95%) of app. +/5 were observed for 88% of all respondents. In tests of validity in discriminating across diagnostic and headache severity groups, relative validity (RV) coefficients of 0.82 and 1.00 were observed for HIT6, in comparison with the Total Score. Patient level classifications based in HIT6 were accurate 88.7% of the time at the recommended cut-off score for a probability of migraine diagnosis. HIT6 was responsive to self reported changes in headache impact. Reference Kosinski M, Bayliss MS, Bjorner JB et al. A six-item short-form survey for measuring headache impact: the HIT-6. Qual Life Res. 2003;12(8): Kosinski M et al. Qual Life Res. 2003;12(8):

Headache Impact Test™-6 (HIT-6)
Score >60 indicates patient is severely impacted or impaired by migraines Speaker’s Notes Kosinski et al. developed a short form Headache Impact Test-6 (HIT6) to assess the impact of headaches that has broad content coverage but is brief, reliable and valid enough to use in screening and monitoring patients in clinical research and practice. HIT6 items were selected from an existing item pool of 54 items and from 35 items suggested by clinicians. The HIT6 was evaluated in an Internet based survey of headache sufferers (n = 1103) who were members of America Online (AOL). After 14 days, 540 participated in a follow up survey. HIT6 covers six content categories represented in widely used surveys of headache impact. Internal consistency, alternate forms, and test retest reliability estimates of HIT 6 were 0.89, 0.90, and 0.80, respectively. Individual patient score confidence intervals (95%) of app. +/5 were observed for 88% of all respondents. In tests of validity in discriminating across diagnostic and headache severity groups, relative validity (RV) coefficients of 0.82 and 1.00 were observed for HIT6, in comparison with the Total Score. Patient level classifications based in HIT6 were accurate 88.7% of the time at the recommended cut-off score for a probability of migraine diagnosis. HIT6 was responsive to self reported changes in headache impact. Reference Kosinski M, Bayliss MS, Bjorner JB et al. A six-item short-form survey for measuring headache impact: the HIT-6. Qual Life Res. 2003;12(8): Kosinski M et al. Qual Life Res. 2003;12(8):

Hospital Anxiety and Depression Scale - Anxiety
Question Frequency Score I feel tense or “wound up” Most of the time A lot of the time Occasionally Not at all 3 2 1 I get a sort of frightened feeling as if something awful is about to happen Very definitely and quite badly Yes, but not too badly A little, but it doesn’t worry me Worrying thoughts go through my mind A great deal of the time From time to time, but not often Only occasionally I can sit at ease and feel relaxed Definitely Usually Not often I get a sort of frightened feeling like “butterflies” in the stomach Quite often Very often I feel restless as I have to be on the move Very much indeed Quite a lot Not very much I get sudden feelings of panic Very often indeed Not very often Not often at all The Hospital and Depression Scale – Anxiety (HADS-A) was developed as a brief measure of generalized symptoms of anxiety and fear. The HADS-A includes specific items that assess generalized anxiety including tension, worry, fear, panic, difficulties in relaxing, and restlessness. The HADS-A has 7 items: three 3 items refer to panic and four refer to generalized anxiety. Respondents indicate how they currently feel on a 4- point Likert scale (range = 0 to 3). The HADS-A evaluates common dimensions of anxiety. It can be used to detect and quantify the magnitude of anxiety symptoms but it cannot detect specific anxiety disorders. Scoring is accomplished by summing scores for items, with special attention given to reversed items. The total score can range from 0 to 21. 0 to 7 = normal or no anxiety 8 to 10 = mild anxiety 11 to 14 = moderate anxiety 12 to 21 = severe anxiety References Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand ;67: Julian LJ. Measures of Anxiety. Arthritis Care Res. (Hoboken) Nov; 63(0 11): /acr Zigmond AS, Snaith RP. Acta Psychiatr Scand. 1983;67:

Mr. LT: Further Tests/Examinations
In this clinical case there is no need for further tests. The only thing that could possibly be proposed is to confirm normality of the clinical examination.

Mr. LT: Diagnosis This patient has the beginnings of medication overuse headache There is an indication for preventative treatment

IHS Diagnostic Criteria for Medication Overuse Headache
Headache occurring on ≥15 days/month in a patient with a pre- existing headache disorder Regular overuse for >3 months of ≥1 drugs that can be taken for acute and/or symptomatic treatment of headache Not better accounted for by another ICHD-3 diagnosis Speaker’s Notes This slide outlines the diagnostic criterial for medication overuse headache according to the International Headache Society. Reference Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9): Link to IHS Diagnosis of Medication Overuse Headache IHS = International Headache Society Headache Classification Committee of the International Headache Society (IHS). Cephalalgia. 2013;33(9):

Medication Overuse Headache (MOH)
New or worsening of existing headache develops in association with medication overuse Headache on ≥15 days/month for >3 months due to overuse of acute medications About 50% of people have MOH Most patients improve after withdrawal of the overused medication Speaker’s Notes Patients with a pre-existing primary headache who, in association with medication overuse, develop a new type of headache or a marked worsening of their existing headache, meet the criteria for medication overuse headache (MOH). MOH is a headache occurring on ≥15 days/month that develops as a consequence of regular overuse of acute or symptomatic headache medication for >3 months. It usually, but not always, resolves after the overuse of medication is stopped. MOH is an interaction between a therapeutic agent used excessively and a susceptible patient. The diagnosis of MOH is extremely important clinically because about 50% of people with headache on ≥15 days/month for >3 months have MOH. Most patients with this disorder improve after discontinuation of the overused medications, as does their responsiveness to preventative treatment. Reference Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9): Headache Classification Committee of the International Headache Society (IHS). Cephalalgia. 2013;33(9):

IHS Classification of Medication Overuse Headaches
Ergotamine-overuse headache Triptan-overuse headache Simple analgesic-overuse headache Opioid-overuse headache Combination-analgesic-overuse headache Medication-overuse headache attributed to multiple drug classes not individually overused Medication-overuse headache attributed to unverified overuse of multiple drug classes Medication-overuse headache attributed to other medication Speaker’s Notes The Headache Classification Committee of the International Headache Society (IHS) divides medication overuse headaches into eight types, as shown on this slide. Reference Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9): IHS = International Headache Society Headache Classification Committee of the International Headache Society (IHS). Cephalalgia. 2013;33(9):

Prescribing Triptans and Monitoring Use
Most effective if taken early in a migraine attack Should not be taken during aura phase Dose should not be repeated if there is no response Dose can be repeated after 2-4 hours if there was initial relief from the migraine and it has reoccurred Avoid using triptans for ≥10 days/month Speaker’s Notes Triptans are most effective if taken early in a migraine attack while the pain is still mild. Triptans should not be taken during the aura phase of a migraine because: Trials in which triptans were administered in the aura phase showed no significant benefit of triptan use over placebo. There are concerns around distinguishing migraine aura from early stroke symptoms, particularly in patients with complex aura presentations. Do not repeat the dose of triptan if not responding to first dose. Individual advice varies for the different triptans but in general patients should not repeat the dose of a triptan if there is no relief of migraine after the first dose. The dose can be repeated after two to four hours if there was initial relief from the migraine and it has then reoccurred. Reference The role of triptans in the treatment of migraine in adults. Best Pract J. 2014;62:28-36. A triptan should be taken early during a migraine attack A triptan should not be taken during the aura phase In absence of a response, the dose of triptan should not be repeated Best Pract J. 2014;62:28-36.

Triptans - Precautions
Limit use to ≤2 days/week Do not use within 24 hour of ergotamine derivatives, other triptans, or methysergide Screen for asymptomatic cardiac disease in patients at risk Common adverse events: Transient feelings of pain or tightness in the chest or throat Tingling Heat Flushing Heaviness or pressure Drowsiness Fatigue Malaise Speaker’s Notes Limit use to ≤2 days/week Do not use within 24 hour of ergotamine derivatives, other triptans, or methysergide Screen for asymptomatic cardiac disease in patients at risk Contraindicated in patients with risk of heart disease, basilar or hemiplegic migraine, or uncontrolled hypertension Common adverse events: Transient feelings of pain or tightness in the chest or throat Tingling Heat Flushing Heaviness or pressure Drowsiness Fatigue Malaise Reference American Headache Society. Brainstorm Available at: _Brainstorm_Syllabus.pdf. Accessed 04 December, 2014. IM = intramuscular; IV = intravenous; SC = subcutaneous American Headache Society. Brainstorm Available at: Accessed 04 December, 2014.

Preventative Therapies in Migraine
For episodic migraine, the AHS Guidelines1 list the following preventive agents as having Level A Evidence: Anti-epilepsy drugs: divalproex sodium, sodium valproate, topiramate Beta blockers: metoprolol, propranolol, and timolol In the EU, flunarazine is felt to have top level evidence2 Recent studies place candesartan as Level A evidence3,4 Some supplements, vitamins, and herbs have evidence for effectiveness5 For chronic migraine, botolinumtoxinA has top level evidence6,7 None of these preventive agents was developed for migraine prophylaxis Speaker’s Notes A variety of preventative therapies are available for the management of migraine, as noted on this slide. The American Headache Society lists a number of anti-epilepsy drugs and beta-blockers as prophylactic medications, while in the EU, flunarizine is felt to have top level evidence. Recent studies have shown candesartan to be effective, while there is also evidence to suggest efficacy of some supplements, vitamins, and herbs. BotulinumtoxinA has top level evidence for chronic migraine. Note that none of these prophylactic drugs was specifically developed for migraine prophylaxis. References Silberstein SD, Holland S, Freitag F et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78: Evers S, Afra J, Frese A et al. EFNS guidelines on the drug treatment of migraine – report of an EFNS task force. Eur J Neurology. 2006;13: Tronvik E, Stovner LJ, Helde G, Sand T, Bovim G. Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial. JAMA. 2003;289:65-9. Stovner LJ, Linde M2, Gravdahl GB et al. A comparative study of candesartan versus propranolol for migraine prophylaxis: A randomised, triple-blind, placebo-controlled, double cross-over study. Cephalalgia. 2013;34: Holland S, Silberstein SD, Freitag F et al. Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology ;78(17): Diener HC, Dodick DW, Aurora SK et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia ;30: Aurora SK, Dodick DW, Turkel CC et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia ;30: AHS = American Headache Society 1. Silberstein SD et al. Neurology. 2012;78: ; 2. Evers S et al. Eur J Neurology. 2006:13: ; 3. Tronvik E et al. JAMA. 2003;289:65-69; 4. Stovner LJ et al. Cephalalgia. 2014; 34:523-32; 5. Holland S et al. Neurology. 2012;78: ; 6. Diener HC et al. Cephalalgia. 2010;30:

Treatment Why start preventative therapy in a woman who has good quality of life? Prevention of medication overuse headache diary/headache diary with high frequency EM (episodic migraine) and beginning of medication overuse (regular use of triptan 2 days/week) Which drug should be used as preventative therapy? Must consider any comorbidities Beta-blockers are contraindicated (she has asthma) Topiramate is indicated because she is overweight NSAID = non-steroidal anti-inflammatory drug

Treatment Objective of preventative therapy: reduce number of headache days and days with acute migraine drug use by ≥50% How can the efficacy of preventative therapy be evaluated? Use a headache diary Speaker’s Notes The objective of migraine prophylactic therapy is to reduce the number of headache days and the number of days with acute migraine drug use by at least half. A headache diary can be used to evaluated the efficacy of prophylactic therapy for migraine.

Patients should record:
Headache Diary Patients should record: Date, time of onset and end Preceding symptoms Intensity on scale Suspected triggers ANY medication taken, including over-the-counter medication – note dosage taken, how many pills the patient took that day Relief (complete/partial/none) Relationship to menstrual cycle Speaker’s Notes Some patients find headache diaries very helpful in identifying and eliminating factors that inﬂuence their headaches. Diaries can be as simple as a notebook or a wall calendar, or be quite elaborate. As a minimum, the patient should try to capture the following information: Time of onset and end Preceding symptoms Intensity on scale Suspected triggers ANY medication taken, including over-the-counter medication – note dosage taken, how many pills the patient took that day Relief (complete/partial/none) Relationship to menstrual cycle The National Institute for Health and Care Excellence (NICE) headache guidelines suggest using a headache diary to help in the diagnosis of primary headache. Patients should record all headache-related information for at least 8 weeks. References American Headache Society. Brainstorm Available at: _Brainstorm_Syllabus.pdf. Accessed 04 December, 2014. National Institute for Health and Care Excellence . Diagnosis and management of headache in young people and adults. CG150. London: NICE; 2012. Available at: Accessed 04 December, 2014. American Headache Society, Available at: National Institute for Health and Care Excellence, 2012. Available at:

Case: Ms. MC Speaker’s Notes
Please introduce the case to the participants.

Ms. MC: Profile 42-year-old female court stenographer
Comes to the clinic complaining of daily headache Has some type of headache every day Taking ASA/acetaminophen (paracetamol)/caffeine combination tablets daily for the pain Headaches wax and wane from mild (1/3) to moderate (1/3) to severe (1/3) Headaches vary in location from bilateral to unilateral to posterior Often awakens with severe headache and neck pain Speaker’s Notes ASA = acetylsalicylic acid (Aspirin)

Ms. MC: History Family history of migraine
History of motion sickness since childhood Began to have non-menstrual headaches in her 20s Headaches lasted 1-2 days Headaches were moderate to severe Headaches got worse with activity Bilateral or unilateral; no predominant side Throbbing, nausea, photophonophobia Treated attacks using ASA/acetaminophen (paracetamol)/caffeine combination Two tablets gave relief but did not render her pain free Invariable recurrence  would take at least 6 tablets/day for the 1-2 days of each attack Speaker’s Notes ASA = acetylsalicylic acid (Aspirin)

Ms. MC: History Headache frequency increased when she was in her 20s and 30s Monthly  twice monthly  twice weekly By her mid- to late-30s she was experiencing headache >15 days per month At least 4 hours daily Increased intake of ASA/acetaminophen (paracetamol)/caffeine tablets Speaker’s Notes ASA = acetylsalicylic acid (Aspirin)

Ms. MC: Medical History Imaging: normal MRI Labs: normal
Physical exam: normal Neurological exam: normal

Ms. MC: Medication History
Numerous acute medications have not worked for her Sumatriptan Metoclopramide + ASA Diclofenac Currently using ASA/acetaminophen (paracetamol)/caffeine combination tablets ASA = acetylsalicylic acid (Aspirin)

Ms. MC: Diagnosis Medication overuse headache
Combination-analgesic-overuse headache subtype Speaker’s Notes

IHS Diagnostic Criteria for Medication Overuse Headache
Headache occurring on ≥15 days/month in a patient with a pre- existing headache disorder Regular overuse for >3 months of ≥1 drugs that can be taken for acute and/or symptomatic treatment of headache Not better accounted for by another ICHD-3 diagnosis Combination-analgesic-overuse headache subtype: Regular intake of ≥1 combination-analgesic medications on ≥10 days/month for >3 months Speaker’s Notes This slide outlines the diagnostic criterial for medication overuse headache according to the International Headache Society. Reference Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9): Link to IHS Diagnosis of Medication Overuse Headache IHS = International Headache Society Headache Classification Committee of the International Headache Society (IHS). Cephalalgia. 2013;33(9):

IHS Classification of Medication Overuse Headaches
Ergotamine-overuse headache Triptan-overuse headache Simple analgesic-overuse headache Opioid-overuse headache Combination analgesic-overuse headache Medication-overuse headache attributed to multiple drug classes not individually overused Medication-overuse headache attributed to unverified overuse of multiple drug classes Medication-overuse headache attributed to other medication Speaker’s Notes The Headache Classification Committee of the International Headache Society (IHS) divides medication overuse headaches into eight types, as shown on this slide. Reference Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9): IHS = International Headache Society Headache Classification Committee of the International Headache Society (IHS). Cephalalgia. 2013;33(9):

Ms. MC: Treatment Establish preventive medication, either a daily medication or botulinumtoxinA. Wean the overused medications as prevention is added. Provide a migraine-specific medication such as a triptan for use on severe attacks, limited to no more than 2 days per week. Instruct Ms. MC not to treat low level headaches Provide behavioral support during this period Speaker’s Notes Reference Tepper SJ. Medication overuse headache. Continuum Lifelong Learning Neurol 2012;18(4):807–822. Tepper SJ. Continuum Lifelong Learning Neurol. 2012;18(4):807–822.

Ms. MC: Follow up Providing regular follow up is very important.
Ms. MC was started on topiramate, was able to tolerate it at 100 mg, and was provided eletriptan for use for her attacks. By 3 months, she was no longer having daily headaches, but had discrete episodic attacks of migraine without aura every 7-10 days, with a sustained pain-free response from the eletriptan. Speaker’s Notes

Ms. MC: Work Up This patient had a long history of episodic migraine and a clear description of transformation to daily headache with increased combination analgesic intake. She had had chronic migraine for years, stable and without change. Her exam was normal and she had had a normal MRI in the past, during the time of daily headaches. Therefore, further workup was not necessary before initiating the treatment. Speaker’s Notes

Case: Ms. HT Speaker’s Notes

Ms. HT: Profile 24-year-old female nurse
Comes to the clinic complaining of headaches Speaker’s Notes ASA = acetylsalicylic acid (Aspirin)

Ms. HT: History Onset of headaches in childhood
Family history of headache and motion sickness Headaches: Episodic, lasting 1 to 3 days (usually at least 2 days), occurring 1 to 2 times per week (usually twice), with an average of at least 10 headache days per month Generally moderate in intensity No antecedent visual or sensory aura; no nausea Bilateral with severe neck pain Often, neck, pain for hours precedes a full blown attack Non-throbbing, but are worse when she bends over or climbs stairs Often awakens with her headaches Headaches do not respond very well to ibuprofen or other over-the-counter analgesics Pattern and frequency of her headaches has not changed in at least 2 years, and her exam is entirely normal. Speaker’s Notes

Classification of Migraine
Migraine without aura Recurrent attacks Attacks and associated migraine symptoms last 4-72 hours Migraine with typical aura Visual and/or sensory and/or speech/language symptoms but no motor weakness Gradual development Each symptom lasts ≤1 hour Mixture of positive and negative features Complete reversibility Chronic Migraine In a patient with previous episodic migraine Headache on ≥15 days/month for >3 months Headache has features of migraine on ≥8 days/month Speaker’s Notes This slide provides the classification of migraine according to the Headache Classification Committee of the International Headache Society (IHS). Reference Headache Classification Committee of the International Headache Society (IHS). Cephalalgia. 2013;33(9): Headache Classification Committee of the International Headache Society (IHS). Cephalalgia. 2013;33(9):

Diagnostic Evaluation for Migraine
Warning signs? HEADACHE Primary Headache Atypical Features Investigations Secondary Headache Diagnosis NO YES Speaker’s Notes This slide presents a simple algorithm for the diagnostic evaluation of migraine. Reference American Headache Society. Brainstorm Available at: _Brainstorm_Syllabus.pdf. Accessed 04 December, 2014. Adapted from Silberstein SD et al. Headache in Clinical Practice. 2nd ed. London: Martin Dunitz; 2002. American Headache Society. Brainstorm Available at: Accessed 04 December, 2014.

IHS Diagnostic Criteria for Migraine without Aura
At least five attacks fulfilling criteria B to D Headache attacks lasting 4 to 72 hours (untreated or unsuccessfully treated) Headache has ≥2 of the following characteristics Unilateral location Pulsating quality Moderate or severe pain intensity Aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs) During headache ≥of the following Nausea and/or vomiting Photophobia and phonophobia Not better accounted for by another ICHD-3 diagnosis Speaker’s Notes This slide presents the diagnostic criteria for migraine without aura according to the International Headache Society (IHS). One or a few migraine attacks may be difficult to distinguish from symptomatic migraine-like attacks. Furthermore, the nature of a single or a few attacks may be difficult to understand. Therefore, at least five attacks are required. Individuals who otherwise meet criteria for migraine without aura but have had fewer than five attacks, should be coded probable migraine without aura. When the patient falls asleep during a migraine attack and wakes up without it, duration of the attack is reckoned until the time of awakening. In children and adolescents (aged <18 years), attacks may last 2-72 hours (the evidence for untreated durations of less than 2 hours in children has not been substantiated). Reference Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9): Link to IHS Diagnosis of Migraine without Aura IHS = International Headache Society Headache Classification Committee of the International Headache Society (IHS). Cephalalgia. 2013;33(9):

Diagnosis: How Ms. HT Fulfills the IHS Criteria
At least five attacks fulfilling criteria B to D Headache attacks lasting 4 to 72 hours (untreated or unsuccessfully treated) Hers last 6 hours to one day Headache has ≥2 of the following characteristics Unilateral location Pulsating quality Moderate or severe pain intensity Aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs) During headache ≥of the following Nausea and/or vomiting Photophobia and phonophobia Not better accounted for by another ICHD-3 diagnosis Speaker’s Notes IHS = International Headache Society Headache Classification Committee of the International Headache Society (IHS). Cephalalgia. 2013;33(9):

Notes on Ms. HT’s Diagnosis of Migraine without Aura
Location does not determine diagnosis Neck pain is very common in migraine, and often precedes head pain as a prodrome1-3 Stress is a very common trigger for migraine4 Moderate pain can occur in migraine, and is part of the ICHD-3 criteria5 Migraine is bilateral 40% of the time6 Episodic disabling headache is usually migraine7 References Blau JN, MacGregor EA. Migraine and the neck. Headache. 1994;34:88-90. Kaniecki RG. Migraine and tension-type headache: an assessment of challenges in diagnosis. Neurology. 2002;58(9 Suppl 6):S15-20. Calhoun AH, Ford S, Millen C et al. The prevalence of neck pain in migraine. Headache ;50: Kelman L. The triggers or precipitants of the acute migraine attack. Cephalalgia ;27: Scharff L, Turk DC, Marcus DA. Triggers of headache episodes and coping responses of headache diagnostic groups. Headache. 1995;35: Headache Classification Committee of the International Headache Society (IHS). Cephalalgia. 2013;33: Lipton RB, Stewart WF, Diamond S et al. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache. 2001;41: Tepper SJ, Dahlöf CG, Dowson A et al. Prevalence and diagnosis of migraine in patients consulting their physician with a complaint of headache: data from the Landmark Study. Headache. 2004;44: 1. Blau JN, MacGregor EA. Headache;34:88-90; 2. Kaniecki RG. Neurology 2002;58 (Suppl 6): S15-20; 3. Calhoun AH et al. Headache. 2010;50:1273-7; 4. Kelman L. Cephalalgia. 2007;27: ; 5. ICHD-3 Beta. Cephalalgia 2013; 33: ; 6. Lipton RB et al. Headache. 2001;41:646-57; 7. Tepper SJ et al. Headache 2004;44:

Ms. HT: Acute Treatment Treatment goal: sustained pain-free response
Oral triptan for her daytime attacks Non-oral triptan for the migraines upon wakening Speaker’s Notes

Preventative Therapies in Migraine
For episodic migraine, the AHS Guidelines1 list the following preventive agents as having Level A Evidence: Anti-epilepsy drugs: divalproex sodium, sodium valproate, topiramate Beta blockers: metoprolol, propranolol, and timolol In the EU, flunarazine is felt to have top level evidence2 Recent studies place candesartan as Level A evidence3,4 Some supplements, vitamins, and herbs have evidence for effectiveness5 For chronic migraine, botolinumtoxinA has top level evidence6,7 None of these preventive agents was developed for migraine prophylaxis Speaker’s Notes A variety of preventative therapies are available for the management of migraine, as noted on this slide. The American Headache Society lists a number of anti-epilepsy drugs and beta-blockers as prophylactic medications, while in the EU, flunarizine is felt to have top level evidence. Recent studies have shown candesartan to be effective, while there is also evidence to suggest efficacy of some supplements, vitamins, and herbs. BotulinumtoxinA has top level evidence for chronic migraine. Note that none of these prophylactic drugs was specifically developed for migraine prophylaxis. References Silberstein SD, Holland S, Freitag F et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78: Evers S, Afra J, Frese A et al. EFNS guidelines on the drug treatment of migraine – report of an EFNS task force. Eur J Neurology. 2006;13: Tronvik E, Stovner LJ, Helde G, Sand T, Bovim G. Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial. JAMA. 2003;289:65-9. Stovner LJ, Linde M2, Gravdahl GB et al. A comparative study of candesartan versus propranolol for migraine prophylaxis: A randomised, triple-blind, placebo-controlled, double cross-over study. Cephalalgia. 2013;34: Holland S, Silberstein SD, Freitag F et al. Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology ;78(17): Diener HC, Dodick DW, Aurora SK et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia ;30: Aurora SK, Dodick DW, Turkel CC et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia ;30: AHS = American Headache Society 1. Silberstein SD et al. Neurology. 2012;78: ; 2. Evers S et al. Eur J Neurology. 2006:13: ; 3. Tronvik E et al. JAMA. 2003;289:65-69; 4. Stovner LJ et al. Cephalalgia. 2014; 34:523-32; 5. Holland S et al. Neurology. 2012;78: ; 6. Diener HC et al. Cephalalgia. 2010;30:

EFNS Guidelines for Initiating Prophylactic Therapy for Migraine
Consider and discuss prophylactic drug when: Quality of life, business duties, or school attendance are severely impaired Patient experiences 2 or more attacks per month Migraine attacks do not respond to acute drug treatment Frequent, very long, or uncomfortable auras occur Speaker’s Notes The decision to introduce a prophylactic treatment must be carefully discussed with the patient. Considerations for individual patients include the eﬃcacy of the drugs, their potential side eﬀects, and their interactions with other drugs. There is no commonly accepted indication for starting a prophylactic treatment. In the view of the European Federation of Neurological Sciences (EFNS)Task Force, prophylactic drug treatment of migraine should be considered and discussed with the patient when: • the quality of life, business duties, or school attendance are severely impaired • frequency of attacks per month is two or higher • migraine attacks do not respond to acute drug treatment • frequent, very long, or uncomfortable auras occur. Migraine prophylaxis is regarded as successful if the frequency of migraine attacks per month is decreased by at least 50% within 3 months. For therapy evaluation, a migraine diary is extremely useful. Reference Evers S, Afra J, Frese A et al. EFNS guideline on the drug treatment of migraine--revised report of an EFNS task force. Eur J Neurol. 2009;16(9): Migraine prophylaxis is regarded as successful if the frequency of migraine attacks per month is decreased by ≥50% within 3 months EFNS = European Federation of Neurological Societies Evers S et al. Eur J Neurol. 2009;16(9):

Ms. HT: Treatment With a stable pattern of ICHD-3 migraine without aura and a normal exam, no imaging study or further work up is necessary. Ms. HT was offered oral sumatriptan for headaches beginning during the day and subcutaneous sumatriptan for headaches full blown upon awakening. Her headache frequency is high, so candesartan 16 mg at bedtime was offered for prevention. She did well, with a 50% reduction in headache frequency and was able to reliably treat each attack with either oral or subcutaneous sumatriptan or use of both sequentially. Speaker’s Notes ICHD = The International Headache Classification

Case: Ms. LG Speaker’s Notes

Ms. LG: Profile 8-year-old female 8-month history of headache
Speaker’s Notes

Discussion Questions what further history would you like to know?
what tests or examinations would you conduct? What red flags would you look for? Speaker’s Notes Ask the questions shown on the slide to stimulate discussion.

Ms. LG’s Headache Characteristics
Bilateral, frontal non-throbbing severe headache that comes on in the later part of the morning Attack frequency: twice per month The girl wants to lie down in a dark, quiet place and not run around She feels better after sleeping Speaker’s Notes

Ms. LG: History Born at term Colicky as a baby
Episodes of unexplained abdominal pain for about a year at age six No other medical problems Normal development Happy at school Mother has a headache with her menses Physical examination is normal Speaker’s Notes

Pediatric Migraine Migraines are common in children
Increase in frequency with increasing age Approximately 6% of adolescents experience migraine Mean age at onset: girls = 10.9 years; boys = 7.2 years Diagnosis is challenging because symptoms can vary significantly throughout childhood Not all adolescents will experience headaches throughout their lives Up to 70% will experience some continuation of persistent or episodic migraines Speaker’s Notes Migraines are common in children and their frequency increases with age to the point where about 6% of adolescents experience migraine. The mean age of onset is lower in boys (7.2 years) than in girls (10.9 years). Because symptoms can vary significantly throughout childhood, diagnosis of migraine in pediatric patients can be challenging. Not all adolescents will grow up to experience migraines in adulthood. However, about 70% of children will experience some continuation of persistent or episodic migraines as adults. References Lewis D, Ashwal S, Hershey A et al. Practice parameter: pharmacological treatment of migraine headache in children and adolescents: report of the American Academy of Neurology Quality Standards Subcommittee and the Practice Committee of the Child Neurology Society. Neurology. 2004;63: Winner P. Pediatric and Adolescent Migraine. Available at: _pediatric_and_Adolescent_Migraine.pdf. Accessed March 31, 2015. Lewis D et al. Neurology. 2004;63: ; Winner P. Pediatric and Adolescent Migraine. Available at: Accessed March 31, 2015.

Key Features for Diagnosis of Pediatric Migraine
Duration tends to be shorter than in adults May be as short as 1 hour but can last 72 hours Often bifrontal or bitemporal rather than unilateral pain Children often have difficulty describing throbbing pain or levels of severity Using a face or numerical pain scale can be helpful Children often have difficulty describing symptoms Symptoms often have to be inferred from the child’s behavior Consider associated symptoms (difficulty thinking, fatigue, lightheadedness) Speaker’s Notes This slide lists the key features of pediatric migraine. Reference Winner P. Pediatric and Adolescent Migraine. Available at: _pediatric_and_Adolescent_Migraine.pdf. Accessed March 31, 2015. Winner P. Pediatric and Adolescent Migraine. Available at: Accessed March 31, 2015.

Red Flags in the Diagnosis of Pediatric Migraine
Increasing frequency and/or severity over several weeks (<4 months) in a child <12 years of age Even more important in children <7 years of age A change of frequency and severity of headache pattern in young children Fever is not a component associated with migraine at any stage – especially in children Headaches accompanied by seizures Altered sensorium may occur in certain forms of migraine but it is not the norm Needs attention to determine appropriate assessment and intervention Speaker’s Notes This slide lists red flags to watch for in the evaluating pediatric patients for migraine. Reference Winner P. Pediatric and Adolescent Migraine. Available at: _pediatric_and_Adolescent_Migraine.pdf. Accessed March 31, 2015. Winner P. Pediatric and Adolescent Migraine. Available at: Accessed March 31, 2015.

Ms. LG: Diagnosis Ms. LG has migraine without aura. Speaker’s Notes

Ms. LG: Treatment Ms. LG was advised to treat her headaches using simple analgesics, such as acetaminophen (paracetamol) or ibuprofen. Speaker’s Notes

Treatment of Pediatric and Adolescent Migraine
Management includes a comprehensive approach: pharmacologic + non-pharmacologic therapies Review dietary triggers Avoid caffeine overuse Avoid head trauma Wear protective headgear whenever appropriate Behavior modification Exercise protocols Proper sleep Speaker’s Notes A comprehensive approach to managing migraines in pediatric patients should be used and it should include pharmacologic and non-pharmacologic treatment options. It is important that dietary triggers be reviewed and that patients be advised to avoid the overuse of caffeine. Patients should avoid head trauma, so should wear protective headgear whenever it is appropriate. Patients should also be counselled on behavior changes that may help with their migraines, as well as on exercise protocols and the need for proper sleep. Reference Winner P. Pediatric and Adolescent Migraine. Available at: _pediatric_and_Adolescent_Migraine.pdf. Accessed March 31, 2015. Lewis D et al. Neurology. 2004;63: ; Winner P. Pediatric and Adolescent Migraine. Available at: Accessed March 31, 2015.

Pharmacotherapies for Pediatric and Adolescent Migraine
Acute therapies should be used as soon as it is clear the headache is migraine Ibuprofen and sumatriptan nasal spray are effective Acetaminophen (paracetamol) is probably effective Almotriptan is the only triptan currently approved by the FDA for treatment of migraine in patients ≥12 years of age Analgesics or acute medications should not be used >2 times per week unless patient is under medical supervision Supplementation with magnesium, riboflavin, and coenzyme Q10 may be helpful No medication currently approved by FDA for migraine prophylaxis in children Some studies have shown topiramate to be effective Speaker’s Notes In pediatric and adolescent headaches, patients should be advised to use their acute therapies as soon as it is clear that their headache is a migraine. Effective acute therapies include ibuprofen and sumatriptan nasal spray; acetaminophen (paracetamol) is also probably effective. Almotriptan is currently the only triptan approved in the US by the FDA for the treatment of migraine in children aged 12 years or older. It is important that pediatric patients not use analgesics or acute medications more than twice per week unless they are under the supervision of a physician. Vitamins and minerals (e.g., magnesium, riboflavin, coenzyme Q10) may be helpful in managing pediatric migraine. There is currently no medication that has been approved by the FDA for migraine prophylaxis in pediatric patients, although topiramate may be effective according to some studies. Reference Winner P. Pediatric and Adolescent Migraine. Available at: _pediatric_and_Adolescent_Migraine.pdf. Accessed March 31, 2015. Lewis D et al. Neurology. 2004;63: ; Winner P. Pediatric and Adolescent Migraine. Available at: Accessed March 31, 2015.

Case: Mrs. PA Speaker’s Notes

Mrs. PA: Profile 43-year-old female who works at home
Twice-monthly attacks of disabling headache over the last two years Speaker’s Notes

Mrs. PA’s Headache Characteristics
Bilateral, frontal throbbing severe pain, worsened with movement Nausea No sound or light sensitivity Cranial allodynia during attacks No aura Bilateral nasal congestion and lacrimation with attacks Attacks last 1-2 days and occur twice a month Speaker’s Notes

Ms. PA: History Her mother had menstrual headache.
Ms. PA’s physical exam is normal.

Mrs. PA: Migraine Medication History
Current uses ASA (Aspirin) with modest benefit Has used paracetamol, ibuprofen, naproxen, and sumatriptan 50 mg (oral) without useful effect Takes propanolol 80 mg daily for mild hypertension Hypertension is well controlled Headache around puberty with menses for 5 years Speaker’s Notes

Menstrual Migraine ~ 60% of female migraine sufferers have menstrual migraines Reduced estrogen at menstruation can trigger migraine in many women May be more persistent, painful, and resistant to treatment than migraines that occur at other times ICHD criteria: Migraine without aura occurring between 2 days prior and 3 days after the onset of menses and in 2 of 3 menstrual cycles Some women experience migraine perimenstrually Headache diary should be used to record timing of menstrual migraines Speaker’s Notes A estimated 60% of female migraine sufferers have menstrual migraines (46% with “menstrually related migraine” and 14% with “pure menstrual migraine”). Reduced estrogen at menstruation can trigger migraine in many women May be more persistent, painful, and resistant to treatment than migraines that occur at other times ICHD criteria: Migraine without aura occurring between 2 days prior and 3 days after the onset of menses and in 2 of 3 menstrual cycles Some women experience migraine perimenstrually Headache diary should be used to record timing of menstrual migraines The drop in estrogen levels that occurs at menstruation can be a powerful trigger for migraine in many women. In patients with menstrual migraine, headaches are predictably timed to the menstrual cycle, although patients also frequently have headaches at other times. Reports from specialty clinics suggest menstrual migraine may be more persistent, painful, and resistant to treatment than migraines that occur at other times, but this finding has not been confirmed in population-based research. Menstrual migraine is not a separate diagnostic category; however, the International Classification of Headache Disorders (ICHD) has established criteria for use in clinical trials of menstrual migraine: migraine without aura occurring between 2 days prior and 3 days after the onset of menses (days −2 through +3) and in 2 of 3 (66%) menstrual cycles. Although menstrual migraine, by definition, is migraine without aura, women may experience migraine with aura perimenstrually. In clinical practice, it is important to assess the relationship between headache onset and menstruation. Timing should be corroborated with a headache diary or calendar; data from these sources are crucial for accurate diagnosis and subsequent treatment planning. Reference Menstrual migraine: breaking the cycle. Available at: Accessed 14 December, ICHD = International Classification of Headache Disorders Menstrual migraine: breaking the cycle. Available at: Accessed 14 December, 2014.

Estrogen Levels and Menstrual Migraine
Speaker’s Notes Levels of estrogen fall during the late luteal phase of the normal menstrual cycle and are at their low point a few days before and after the onset of menses. Estrogen decline is the primary trigger of menstrual migraine. A study of 38 women with menstrual migraine found that the cyclic decline in estrogen levels was inversely proportional to the prevalence of migraines, as shown in the graph on this slide. It has been hypothesized that as estrogen levels decline, there is a concurrent drop in levels of brain serotonin (5-hydroxytryptamine [5-HT]) or endorphin levels, which makes the patient more vulnerable and sensitive to pain. Other mechanisms that are unrelated to estrogen may also contribute to menstrual migraine. These include elevated prostaglandins (possibly due to endometrial prostaglandin production), decreased responsiveness to endogenous opioid activity (decreased opioid tonus), and a decline in circulating ionized magnesium levels. The exact mechanisms of menstrual migraine, however, are not fully understood. Reference Menstrual migraine: breaking the cycle. Available at: Accessed 14 December, 2014. Menstrual migraine: breaking the cycle. Available at: Accessed 14 December, 2014.

Mrs. PA: Diagnosis Ms. PA has migraine without aura. Speaker’s Notes

Mrs. PA: Treatment Rizatriptan (10 mg po) or eletriptan (40 mg po) could be prescribed to Mrs. PA. Speaker’s Notes

Mrs. PA: Follow-up Mrs. PA should be followed up in two to three months to see how her treatment is working. Speaker’s Notes

Case: Ms. MY Speaker’s Notes

Ms. MY: Profile 21-year-old female office secretary
Complains of a left-sided throbbing headache Symptoms started at age 15 Have occurred once or twice a month since then Notices flashes of white light followed by a unilateral pulsating headache after a few minutes during her episodes Prefers to stay in a dark, quiet room Adequate rest, sleep, and mefenamic acid or ibuprofen have failed to relieve her headaches in the last 3 months She would only get partial relief from the NSAIDs Speaker’s Notes NSAID = non-steroidal anti-inflammatory drug

Ms. MY: History No weakness, numbness or dizziness
Unremarkable past history Unremarkable neurologic exam Ms. MY is not taking any medications or oral contraceptives Her mother reportedly also had throbbing headaches during adolescence Speaker’s Notes

Ms. MY: Diagnosis This patient has migraine with aura

Ms. MY: Treatment Strategy
Neurologist recommends that the patient take a triptan Patient indicates she wants to take only over-the-counter medications because they used to help her Her neighbour advised her to take a coxib Ms. MY is considering doing this in her next migraine attack Speaker’s Notes

Ms. MY: Recommended Treatment Strategy
Since patient presents with migraine headache once or twice a month with NSAID failure, recommended therapy according to CHS guidelines for acute migraine therapy would be: NSAID + triptan rescue Triptan Reference Worthington I, Pringsheim T, Gawel MJ et al. Pharmacological acute migraine treatment strategies: choosing the right drug for a specific patient. Can J Neurol Sci. 2013;40(5 Suppl 3):S33-S62. CHS = Canadian Headache Society; NSAID = non-steroidal anti-inflammatory drug Worthington I et al. Can J Neurol Sci. 2013;40(5 Suppl 3):S33-S62.

Ms. MY: Follow Up Regular follow up with attending physician is recommended to assess treatment efficacy Any changes in the character of headache or the presence of red flags warrants immediate reassessment

Case: Ms. BD Speaker’s Notes

Ms. BD: Profile 25-year-old female sales agent
Diagnosed with migraine headache Migraines started around age 13 Migraines are intermittent unilateral throbbing headaches Occur 3 to 4 times per year No aura During attacks, Ms. BD becomes nauseated and vomits several times This restricts the use of oral medications Speaker’s Notes

Ms. BD: History No comorbid conditions Neurologic exam is unremarkable
Speaker’s Notes

Ms. BD: Further History No family history of chronic headaches, intracranial tumors, or lesions Not a smoker, not an alcoholic beverage drinker, denies drug use Speaker’s Notes

Ms. BD: Further Testing Stable headache Normal neurologic examination
Nausea and vomiting May be a sign of increased intracranial pressure Midline lesions may not show any focal neurologic deficit and present only with headache, nausea and vomiting Imaging may be done – ideally cranial MRI with contrast Speaker’s Notes

Ms. BD: Red Flags Nausea and vomiting in this present case
Particular attention to character, intensity of headaches and accompanying manifestations (e.g., new kind of headache [non-throbbing, progressive] Such severe intensity for the first time (from usual VAS 4 to 7 to VAS 8 to 10) Accompanied by diplopia, lateralizing signs and altered consciousness Speaker’s Notes VAS = Visual Analog Score

Choosing a Triptan All triptans have similar efficacy
Base choice on patient preference Patients often prefer oral therapy Vomiting and nausea may preclude use of oral treatment consider subcutaneous or nasal formulations Patients who do not respond to one triptan may respond to a different one Try an alternative triptan in a subsequent attack Patients who do not respond to oral triptans should be encouraged to try subcutaneous formulations Speaker’s Notes Because all triptans have similar efficacy it is appropriate to select a triptan based on patient preference. Patients often prefer oral treatment. Moreover, vomiting and nausea may restrict oral treatment for some patients. In such cases, an alternative form of treatment such as subcutaneous or intranasal triptan can be used. “Melt” preparations dissolve on the tongue and are only absorbed after swallowing. They may be useful for people who find drinking water intolerable during a migraine or who are unable to swallow tablets, but are not usually suitable if vomiting is problematic. Patients who do not respond to one triptan may respond to another. Therefore, it is reasonable to try an alternative triptan for a subsequent attack if one proves to be ineffective. In particular, patients who do not respond to oral triptans should be encouraged to try a subcutaneous formulation. Reference The role of triptans in the treatment of migraine in adults. Best Pract J. 2014;62:28-36. Best Pract J. 2014;62:28-36.

Triptans: Treatment Choices
Sumatriptan Tablet and fast-disintegrating Injection Nasal spray Rizatriptan Tablet and melt Zolmitriptan Almotriptan Tablet Naratriptan Frovitriptan Eletriptan Speaker’s Notes Several triptans are currently available. The first is sumatriptan. The oral formulation is available in 25-mg, 50-mg and 100-mg doses as either an oral tablet or a rapidly- dissolving tablet. Since its introduction in the early 1990s, over 400 million doses of sumatriptan have been given. Zolmitriptan, the second product in the triptan class, has a longer half-life than sumatriptan and a more rapid Tmax. It is available as a tablet, orally disintegrating tablet, and as a nasal spray. Naratriptan has a longer half-life than sumatriptan, and lower recurrence rate. Naratriptan is considered to have lower efficacy than sumatriptan with minimal adverse events. Rizatriptan has a rapid onset of action and a shorter Tmax of 1 hour compared to oral sumatriptan. This product is available as a tablet and in a dissolvable wafer form. Almotriptan is available as an oral tablet and has a good adverse event profile. Frovatriptan is available as a tablet. It, like naratriptan, has a long half-life, low rate of adverse events, and a low recurrence rate. Eletriptan is available as an oral tablet. References Ferrari MD, Roon KI, Lipton RB, Goadsby PJ. Oral triptans (serotonin 5-HT(1B/1D) agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet ;358(9294): Worldwide Product Safety and Pharmacovigilance Document. December 1999. Ferrari MD et al. Lancet. 2001;358(9294): ; Worldwide Product Safety and Pharmacovigilance Document. December 1999.

Pharmacokinetic Properties of Triptans
Onset of Efficacy (min) Time to Peak Levels (h) Lipophilicity Bioavailability (%) Elimination t1/2 (h) Elimination Routes Almotriptan 45-60 Unknown 80 3.5 Hepatic (active metabolite) Renal, MAO, CYP Eletriptan 60 High 50 4-5 CYP Frovatriptan Up to 4 hours 2-4 Low 24-30 26 Hepatic, CYP Naratriptan 2-3.5 63-73 5-6 Hepatic, renal, CYP Rizatriptan 30 1 Moderate 45 2-2.5 Hepatic, MAO, renal Sumatriptan 2-3 14 Hepatic, MAO Zolmitriptan 1-1.5 40-48 2.5-3 MAO, CYP Speaker’s Notes All triptans are associated with “triptan sensations”, which are symptoms of burning, tingling, or tightness in the face, neck, limbs or chest. Chest pressure may be alarming for the patient; however, in most cases it is not associated with electrocardiogram (ECG) changes or other evidence of decreased myocardial perfusion. Triptan dose may be lowered in patients who are very sensitive to the adverse effects. Triptan use has been associated with serious cardiovascular events, including death. Most cases had prior cardiovascular risk factors. Patients with multiple cardiac risk factors may need cardiac evaluation before triptans are initiated. Triptans are contraindicated in people with uncontrolled or severe hypertension, ischaemic heart disease, or previous myocardial infarction, stroke or coronary vasospasm (including Prinzmetal’s angina) due to their vasoconstrictive effect. Reference Belvís R, Pagonabarraga J, Kulisevsky J. Individual triptan selection in migraine attack therapy. Recent Pat CNS Drug Discov. 2009;4(1):70-81. Rizatriptan provides the fastest onset of efficacy CYP = cytochrome hepatic system; MAO = monoamine oxidase A Belvís R et al. Recent Pat CNS Drug Discov. 2009;4(1):70-81.

Prescribing Triptans and Monitoring Use
Most effective if taken early in a migraine attack Do not take during aura phase Dose should not be repeated if there is no response Dose can be repeated after two to four hours if there was initial relief from the migraine and it has reoccurred Avoid using triptans for ≥10 days/month Speaker’s Notes Triptans are most effective if taken early in a migraine attack while the pain is still mild. Triptans should not be taken during the aura phase of a migraine because: Trials in which triptans were administered in the aura phase showed no significant benefit of triptan use over placebo. There are concerns around distinguishing migraine aura from early stroke symptoms, particularly in patients with complex aura presentations. Do not repeat the dose of triptan if not responding to first dose. Individual advice varies for the different triptans but in general patients should not repeat the dose of a triptan if there is no relief of migraine after the first dose. The dose can be repeated after two to four hours if there was initial relief from the migraine and it has then reoccurred. Reference The role of triptans in the treatment of migraine in adults. Best Pract J. 2014;62:28-36. A triptan should be taken early during a migraine attack A triptan should not be taken during the aura phase In absence of a response, the dose of triptan should not be repeated Best Pract J. 2014;62:28-36.

Triptans: Contraindications
Pregnancy Lactation Ischemic stroke Ischemic heart disease Prinzmetal’s angina Raynaud’s disease Uncontrolled hypertension Severe liver or renal failure Familial hemiplegic migraine Basilar migraine Ergotamine therapy MAOI therapy Speaker’s Notes All triptans are associated with “triptan sensations”, which are symptoms of burning, tingling, or tightness in the face, neck, limbs or chest. Chest pressure may be alarming for the patient; however, in most cases it is not associated with electrocardiogram (ECG) changes or other evidence of decreased myocardial perfusion. Triptan dose may be lowered in patients who are very sensitive to the adverse effects. Triptan use has been associated with serious cardiovascular events, including death. Most cases had prior cardiovascular risk factors. Patients with multiple cardiac risk factors may need cardiac evaluation before triptans are initiated. Triptans are contraindicated in people with uncontrolled or severe hypertension, ischaemic heart disease, or previous myocardial infarction, stroke or coronary vasospasm (including Prinzmetal’s angina) due to their vasoconstrictive effect. Reference Belvís R, Pagonabarraga J, Kulisevsky J. Individual triptan selection in migraine attack therapy. Recent Pat CNS Drug Discov. 2009;4(1):70-81. MAO = monoamine oxidase Belvís R et al. Recent Pat CNS Drug Discov. 2009;4(1):70-81.

Ms. BD: Follow Up Cranial imaging Assess response to treatment
Changes in the character of headache and the presence of other red flags warrant reassessment Speaker’s Notes

References Speaker’s Notes
American Headache Society. Brainstorm Available at: Accessed 04 December, Aurora SK, Dodick DW, Turkel CC et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia. 2010;30: Beck E, Sieber WJ, Trejo R. Management of cluster headache. Am Fam Physician. 2005;71(4): Belvís R, Pagonabarraga J, Kulisevsky J. Individual triptan selection in migraine attack therapy. Recent Pat CNS Drug Discov. 2009;4(1): Blau JN, MacGregor EA. Migraine and the neck. Headache. 1994;34: Calhoun AH, Ford S, Millen C et al. The prevalence of neck pain in migraine. Headache. 2010;50: Cramer JA, Silberstein SD, Winner P. Development and validation of the Headache Needs Assessment (HANA) survey. Headache. 2001;41(4): Diener HC, Dodick DW, Aurora SK et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia. 2010;30: Dodick DW, Campbell JK. Cluster headache: diagnosis, management and treatment. In: Silberstein SD, Lipton RB, Dalessio DJ, eds. Wolff’s Headache And Other Head Pain. 7th ed. New York, NY: Oxford University Press; 2001: Evers S, Afra J, Frese A et al. EFNS guidelines on the drug treatment of migraine – report of an EFNS task force. Eur J Neurology. 2006;13: Ferrari MD, Roon KI, Lipton RB, Goadsby PJ. Oral triptans (serotonin 5-HT(1B/1D) agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet. 2001;358(9294): Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9): Holland S, Silberstein SD, Freitag F et al. Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78(17): Julian LJ. Measures of Anxiety. Arthritis Care Res. (Hoboken) Nov; 63(0 11): /acr Kaniecki RG. Migraine and tension-type headache: an assessment of challenges in diagnosis. Neurology. 2002;58(9 Suppl 6):S15-20. Speaker’s Notes

Kelman L. The triggers or precipitants of the acute migraine attack. Cephalalgia. 2007;27: Kosinski M, Bayliss MS, Bjorner JB et al. A six-item short-form survey for measuring headache impact: the HIT-6. Qual Life Res. 2003;12(8): Lewis D, Ashwal S, Hershey A et al. Practice parameter: pharmacological treatment of migraine headache in children and adolescents: report of the American Academy of Neurology Quality Standards Subcommittee and the Practice Committee of the Child Neurology Society. Neurology. 2004;63: Lipton RB, Stewart WF, Diamond S et al. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache. 2001;41: Martin VT. Menstrual migraine: new approaches to diagnosis and treatment. Available at: Accessed March 26, Menstrual migraine: breaking the cycle. Available at: Accessed 14 December, National Institute for Health and Care Excellence . Diagnosis and management of headache in young people and adults. CG150. London: NICE; Available at: Accessed 04 December, Scharff L, Turk DC, Marcus DA. Triggers of headache episodes and coping responses of headache diagnostic groups. Headache. 1995;35: Silberstein SD, Holland S, Freitag F et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78: Stewart WF, Lipton RB, Dowson AJ, Sawyer J. Development and testing of the Migraine Disability Assessment (MIDAS) Questionnaire to assess headache-related disability. Neurology. 2001;56(6 Suppl 1):S20-8. Stovner LJ, Linde M2, Gravdahl GB et al. A comparative study of candesartan versus propranolol for migraine prophylaxis: A randomised, triple-blind, placebo-controlled, double cross-over study. Cephalalgia. 2013;34: Tepper SJ, Dahlöf CG, Dowson A et al. Prevalence and diagnosis of migraine in patients consulting their physician with a complaint of headache: data from the Landmark Study. Headache. 2004;44: Speaker’s Notes

Tepper SJ, Dahlöf CG, Dowson A et al. Prevalence and diagnosis of migraine in patients consulting their physician with a complaint of headache: data from the Landmark Study. Headache. 2004;44: Tepper SJ. Medication overuse headache. Continuum Lifelong Learning Neurol. 2012;18(4):807–822. The role of triptans in the treatment of migraine in adults. Best Pract J. 2014;62: Tronvik E, Stovner LJ, Helde G, Sand T, Bovim G. Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial. JAMA. 2003;289:65-9. Ware, JE Jr. SF-36® Health Survey Update. Available at: Accessed 03 December, Winner P. Pediatric and Adolescent Migraine. Available at: Accessed March 31, Worldwide Product Safety and Pharmacovigilance Document. December Worthington I, Pringsheim T, Gawel MJ et al. Pharmacological acute migraine treatment strategies: choosing the right drug for a specific patient. Can J Neurol Sci. 2013;40(5 Suppl 3):S33-S62. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67: Speaker’s Notes

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