1. MIGRAINE HEADACHE ANTONIA C CHALMERS, MD

2. PREVALENCE Migraine is the most prevalent neurological disorder. More than 80 million people suffer migraine headaches in US and Europe 28 million people in the US older than age 12 21 million females, 7 million males The ratio of female to male is 3:1 Migraine Prevalence peaks between 35 and 45 Migraine is so common that 1 in 4 households has one with migraine There seems to be a genetic predisposition

3. DEFINITION Migraine headache is a result of specific changes within the brain. Migraine is a complex disorder characterized by recurring headaches, often unilateral. Headaches can be associated with visual or sensory aura. The aura often precede the head pain but may occur during or after the head pain. Migraine is most common among women and has a genetic component. A variety of environmental and behavioral factors may precipitate migraine attacks in persons with a predisposition to migraine

4. MIGRAINE TRIGGERS Hormonal Stress Excessive or insufficient sleep Medications : BCP, vasodilators Smoking Exposure to bright lights and strong odors Head trauma Weather changes Motion sickness Fasting or skipping meals Certain foods and preservatives : chocolate, nitrates, aged cheeses, MSG Alcohol Lack of exercise

5. PATHOPHYSIOLOGY OF MIGRAINE Neurovascular theory : -neurogenic process with secondary changes in cerebral perfusion associated with a sterile neurogenic inflammation -At baseline, a migraineur who is not having any headache has a state of neuronal hyperexcitability in the cerebral cortex. This explains the susceptibility of the migrainous brain to headaches.

6. PATHOPHYSIOLOGY OF MIGRAINE Cortical spreading depression ( CSD): -Oligemia : CSD of Leao: wave of neuronal excitation in the cortical gray matter that spreads from the site of origin at the rate of 2-6 mm/min. This is responsible for the aura. This in turn, activates the trigeminal fibers, causing the headache phase. -Trigeminovascular system (TVS) : Activation of the TVS by CSD stimulates the release of pain generating substances such as Calcitonin gene related peptide, substance P, vasoactive intestinal peptides, and Neurokinin A. This leads to sterile inflammation, vasodilatation and protein extravasation producing pain.

7. SEROTONIN AND MIGRAINE Serotonin receptors ( 5hydroxytryptamine [ 5HT] ) is the most important receptor in headache pathway. 5HT 1D receptors are present in the trigeminal sensory neurons and 5HT1 B on smooth muscle cells in meningeal vessels and coronary vessels. The Triptans are selective 5 HT1B/D agonists and prevent the release of neuropeptides and block neurotransmission.

8. SIGNS AND SYMPTOMS HEAD PAIN: Throbbing or pulsating pain, moderate to severe Pain aggravated by activity and movement Pain often unilateral but can be bilateral or global : 50% unilateral and 40% bilateral Headache lasts for 4-72 hours in adults and 2-48 hours in children Systemic symptoms often present: light/noise sensitivity, nausea/vomiting, lightheadedness 1/3 of patients experience an aura

9. MIGRAINE AURA May precede or accompany the headache phase or may occur in isolation Usually develops over 5-20 minutes and last less than 60 minutes Most commonly visual but can be sensory, motor or combination of these Visual aura can be positive or negative The most common positive visual aura is the scintillating scotoma, an arc of absent vision with shimmering zigzag border

10. DIAGNOSIS: ICHD II CRITERIA FOR MIGRAINE WO AURA Must have had at least 5 headache attacks that lasted for 4-72 hours with at least 2 of the following characteristics: -Unilateral location -Pulsating Quality -Moderate to severe pain intensity -Aggravated by routine activity In addition, during the headache phase, the patient must have at least 1 of the following: -Nausea and/or vomiting -Photophobia and/or phonophobia -Headaches cannot be attributed to another disorder HEADACHE CLASSIFICATION COMMITTEE OF THE INTERNATIONAL HEADACHE SOCIETY

11. MIGRAINE VARIANTS Childhood periodic syndromes Late life migrainous accompaniments Basilar Migraine Hemiplegic Migraine Retinal Migraine

12. HIS CLASSIFICATION : ICHD-2 Primary headache -symptoms based -tools now available to help measure/monitor patient disability Secondary headache -etiology based Red flags can help separate the diagnosses

13. SECONDARY HEADACHES RED FLAGS“SSNOOP” S ystemic symptoms (fever, weight loss) S econdary risk factors: underlying disease ( HIV, systemic illness, cancer) N eurologic symptoms or abnormal signs (confusion, impaired alertness, or consciousness) O nset : sudden, abrupt, or split second ( first, worst) O lder: new onset and progressive headache, especially in the middle age >50( giant cell arteritis) P revious headache history or headache progression: pattern change, first headache or different (change in attack frequency, severity, or clinical features)

14. DIAGNOSTIC TESTS Selection of laboratory/imaging studies to rule out conditions other than migraine headache is determine by the clinical presentation and examination. Sed rate and CRP for patients above 50 years of age to ro temporal arteritis Neuroimaging is not necessary is patients with a history of recurrent migraine headaches and a normal neurological examination

15. DIAGNOSTIC TESTING: CT AND MRI In patients with migraine, neither CT nor MRI is warranted except in cases with : -recent substantial change in headache pattern -history of seizures -focal neurological symptoms or signs -red flags Consensus expert opinion -MRI is more sensitive

16. MANAGEMENT OF MIGRAINE Acute or abortive treatment with the goal of return to function. Early intervention is essential. Preventive treatment with the goal of preventing more attacks

17. ACUTE VS PREVENTIVE THERAPY Acute ( Abortive ) Taken after attack has begun to relieve pain and disability and stop progression Preventive Taken daily to reduce attack frequency severity and duration Patients taking preventive medication can also use acute medication

18. MANAGEMENT Acute/abortive medications: Selective serotonin receptor agonists: Triptans Ergot alkaloids i.e. ergots, dihydroergotamine ( DHE) Analgesics Nonsteroidal Anti-infammatory drugs (NSAIDS) Combination products Anti emetics

19. ACUTE THERAPIES FOR MIGRAINE Specific : Ergotamine or dihydroergotamine Triptans: Sumatriptan, Rizatriptan, Zomitriptan, Almotriptan, Eletriptan, Naratriptan and Frovatriptan Non specific: pain killers (non narcotics, narcotics, combination medications ), anti emetics

20. CONSIDERATIONS FOR PREVENTIVE TX Headaches cause major disruption in patient’s lifestyle, with significant disability that lasts 3 or more days Prolonged and frequent headaches. More than 1 headache per week. Abortive therapy fails/ineffective, contraindicated or is overused Symptomatic medications are contraindicated or ineffective Use of abortive medications more than 2x per week Migraine variants such as hemiplegic migraine *Preventive treatment reduces the progression to more frequent and more severe headaches and improves responsiveness to abortive treatment.

21. PRINCIPLES OF PREVENTIVE DRUG TX Start with low dose and increase slowly Need adequate trial ( 2-3 months) Avoid drug overuse and interfering drugs Evaluate therapy -use migraine calendar/diary -consider taper or stop if HA well controlled Take co existing conditions into account -determine contraindications (eg, pregnancy) to minimize potential risks

22. MANAGEMENT Preventive treatment - anti epileptic drugs: Topiramate, sodium valproate -beta blockers: propranolol, metoprolol, timolol -Tricyclic antidepressants -Calcium Channel blockers -Selective serotonin reuptake inhibitors (SSRI) -NSAIDs -Botulinum toxin -non pharmacologic : biofeedback, avoid triggers, exercise

23. MIGRAINE COMORBIDITY MAY ASSIST WITH SELECTION OF PREVENTIVE AGENT Comorbidity Agent Anxiety SSRI/SNRI, AED Bipolar AED, SSRI/SNRI Depression TCA Epilepsy AED Insomnia TCA MVP B blocker Raynaud Calcium blocker

24. MANAGEMENT Alternative medicine - reduction of migraine triggers ( eg, stress, certain foods, lack of sleep, hunger, fatigue ) -non pharmacologic therapy: biofeedback, cognitive-behavioral therapy -integrative medicine ; butterbur, riboflavin 400mg, magnesium 400mg, feverfew, coenzyme Q10

25. SYNDROME OF MEDICATION OVERUSE HEADACHE (MOH) Also maybe known as rebound headache Occurs in patients with preexisting migraine/pain Pattern of headaches and overuse of analgesics and other drugs in critical monthly doses and frequencies Prevention limit frequency and dose of meds Treatment refractory to otherwise appropriate therapy -withdrawal therapy -restriction of monthly doses for acute treatment

26. PRINCIPLES OF MOH THERAPY Taper medications most likely causing MOH/rebound headache Substitute acute medications that do not cause MOH/rebound headache Consider synergistic combination therapy Cautions: Opiate and barbiturate abstinence syndrome Increasing headache during withdrawal period

27. SUMMARY Migraine headache is a brain disorder manifested with recurring headaches associated with systemic symptoms. Pain is often unilateral. It is very common in young women. There are triggers which should be managed. There was a number of acute therapies both specific and non specific, that are used to lessen the severity o the headache. Timing is crucial, especially when using acute medications like the Triptans. Early use of Triptans results in better outcomes, less recurrence, and fewer adverse events. There are preventive medications to be used when acute therapy fails, are contraindicated or the headaches are prolonged or too frequent.

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