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Diagnosis and management of migraine, a primary headache

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1 Migraine: Diagnosis and Management Dr. (Med) Freda Dodd-Glover Neurologist KBTH
2 Outline • Primary Headaches overview • Pathophysiology of migraine • Acute management • Prophylactic management • Case discussion
3 What is a Headache? • Pain or discomfort affecting any part of the head arising from pain- sensitive structures. • Pain located in the head, above the orbitomeatal line and/or nuchal ridge. Headache Facial Pain
4 International Classification of Headache Disorders (ICHD-3) The ICHD-3 criteria defines three major categories of disorders: • primary headaches • secondary headaches • cranial neuralgias and facial pain
5 Primary Headaches • Multiple entities causing episodic and chronic head pain/discomfort in the absence of underlying medical conditions, medications or traumatic injury. • Primary headache disorders include: • Migraine • Tension-Type Headache(TTH) • Trigeminal Autonomic Cephalalgias(TACS) • Other primary headache disorders
6
7 Infrequent episodic Tension Type Headache (TTH) Diagnostic criteria: A. At least 10 episodes of headache occurring on <1 day/month on average (<12 days/year) and fulfilling criteria B-D B. Lasting from 30 minutes to 7 days C. At least two of the following four characteristics: A. bilateral location B. pressing or tightening (non-pulsating) quality C. mild or moderate intensity D. not aggravated by routine physical activity such as walking or climbing stairs D. Both of the following: A. no nausea or vomiting B. no more than one of photophobia or phonophobia E. Not better accounted for by another ICHD-3 diagnosis
8 Frequent episodic TTH Diagnostic criteria: A. At least 10 episodes of headache occurring on 1-14 days/month on average for >3 months (≥12 and <180 days/year) and fulfilling criteria B-D B. Lasting from 30 minutes to 7 days C. At least two of the following four characteristics: A. bilateral location B. pressing or tightening (non-pulsating) quality C. mild or moderate intensity D. not aggravated by routine physical activity such as walking or climbing stairs D. Both of the following: A. no nausea or vomiting B. no more than one of photophobia or phonophobia E. Not better accounted for by another ICHD-3 diagnosis.
9 Chronic TTH Diagnostic criteria: A. Headache occurring on ≥15 days/month on average for >3 months (≥180 days/year), fulfilling criteria B-D B. Lasting hours to days, or unremitting C. At least two of the following four characteristics: A. bilateral location B. pressing or tightening (non-pulsating) quality C. mild or moderate intensity D. not aggravated by routine physical activity such as walking or climbing stairs D. Both of the following: A. no more than one of photophobia, phonophobia or mild nausea B. neither moderate or severe nausea nor vomiting E. Not better accounted for by another ICHD-3 diagnosis.
10 Trigeminal Autonomic Cephalalgias (TACs) • A distinct set of headaches typified by shorter-lasting attacks of unilateral intense pain in the trigeminal distribution with ipsilateral cranial autonomic symptoms. • Cluster headaches • Paroxysmal hemicrania • Short-lasting unilateral neuralgiform headache attack (SUNHA) syndromes • Hemicrania continua
11 Trigeminal Autonomic Cephalalgias (TACs) • Characteristic Features: • Side-locked • V1 distribution predominantly • Shorter-lasting (with the exception of hemicrania continua) • Intense severity • Autonomic features overshadow nausea, photophobia, or phonophobia • Ptosis Forehead/facial sweating/flushing • Miosis Lacrimation • Periorbital oedema Aural fullness • Rhinorrhoea
12 Cluster Headaches
13 What are Migraines? • A Migraine is a complex neurological disorder characterized by recurrent episodes of headaches mostly unilateral. • It may be associated with visual, sensory, motor, speech or brainstem symptoms— collectively known as aura. • Aura may arise most often before the head pain but that may occur during or afterward the headache.
14 What are Migraines?
15 What are Migraines? • Africa has an estimated fifty-six million people living with migraine. • World-wide prevalence is approximately 14-15 % • African studies report 5-10% • Male to female ratio of approximately 1:3
16 Classification of Migraine • Migraine without aura (formerly, common migraine) • Probable migraine without aura • Migraine with aura (formerly, classic migraine) • Probable migraine with aura • Episodic migraine • Chronic migraine • Chronic migraine associated with analgesic overuse • Childhood periodic syndromes that may not be precursors to or associated with migraine - these syndromes include cyclic vomiting, abdominal migraine, and benign paroxysmal vertigo of childhood.
17 IHS Classification – ICHD 3:Migraine with aura The following criteria must be met: One or more visual, sensory, speech, motor, brainstem, or retinal symptoms, as well as at least 2 of the following 4 criteria: (1) at least 1 aura symptom spreading gradually over 5 or more minutes and/or 2 or more symptoms occurring in succession (2) each aura symptom lasting 5–60 minutes (3) at least 1 aura symptom being unilateral (4) the aura being accompanied by or followed shortly by headache (5) Not better accounted for by another ICHD-3 diagnosis.
18 IHS Classification – ICHD 3:Migraine without aura A. At least five attacks fulfilling criteria B–D B. Headache attacks lasting 4-72 hours (untreated or unsuccessfully treated) C. Headache has at least two of the following four characteristics: 1. unilateral location 2. pulsating quality 3. moderate or severe pain intensity 4. aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs) D. During headache at least one of the following: 1. nausea and/or vomiting 2. photophobia and phonophobia E. Not better accounted for by another ICHD-3 diagnosis. Memory Aid: 5-4-3-2-1 rule
19 Migraine classification and variants • Chronic migraine : > 15 days a month for 3 consecutive months with 8 of days fulfilling migraine criteria. • Episodic migraine: < 15 days a month • Status migrainosus: migraine lasting more than 72hours • Ophthalmoplegic migraine: 3rd nerve palsy, ptosis, ocular muscle paralysis . • Hemiplegic migraine. • Migraine equivalent (acephalgic): aura without migraine. Seen in persons with recurrent headaches, mostly older than 40.
20 Pathophysiology The key structures involved in migraine include: • the large intracranial vessels, dura mater and peripheral terminals of the trigeminal nerve that innervate these structures (the trigeminovascular complex) • the caudal portion of the trigeminal nucleus, which extends into the dorsal horns of the upper cervical spinal cord and receives input from the first and second cervical nerve roots (the trigeminocervical complex) • rostral pain-processing regions, such as the ventroposteromedial thalamus and the cortex . • the pain-modulatory systems in the brain that modulate input from trigeminal nociceptors at all levels of the pain-processing pathways.
21 Pathophysiology •Source: Harrison Neurology 3rd Edition
22 Pathophysiology • Genetically susceptible / hyperexcitable brain • ?Cortical spreading depression • Calcitonin Gene-Related Peptide • Substance P • Neurokinin A • Nitric Oxide • Serotonin • Cyclic adenosine monophosphate Oguzhan et al, Migraine and neuroinflammation, the inflammasome perspective, J. Headache Pain,22:55(2021)
23 Acute Management • Once a diagnosis of migraine has been established, it is important to assess the extent of a patient’s disease and disability. • The Migraine Disability Assessment Score (MIDAS) is a well-validated, easy-to-use tool. • Assessment and management of associated comorbidities is key. PHQ2, PHQ9, MSQ, SF-36
24
25 Acute Management – Patient education Patient education is an important aspect of migraine management. • It is helpful for patients to understand that migraine is an inherited tendency to headache • that migraine can be modified and controlled by lifestyle adjustments and medications • it cannot be eradicated; • except in women with migraine with aura on oral estrogens or combined oral contraceptives, migraine is not associated with serious or life-threatening illnesses. (migraine with aura : 2-3-fold increase in strokes) Curtis KM et al. Use of combined oral contraceptives among women with migraine and non-migrainous headaches. 2006;73:189-194. doi 10.1016/ j.contraception. 2005.08.009
26 Acute Management – Non-pharmacologic HEADACHE DIARY AVOID TRIGGERS HEALTHY DIET REGULAR EXERCISE REGULAR SLEEP PATTERNS AVOIDANCE OF EXCESS CAFFEINE AND ALCOHOL AVOIDANCE OF ACUTE CHANGES IN STRESS LEVELS
27 Acute Management- Pharmacologic • Judicious use of appropriate medications • The optimal regimen is individualized and depends on a number of factors: severity of the attack being key. • Mild migraine attacks can usually be managed by oral agents ( the average efficacy rate is 50–70%). • Severe migraine attacks may require parenteral therapy.
28 Acute Management- Pharmacologic The ideal acute/abortive medication should have/provide: • minimal / no adverse effects • Little requirement for repeat dosing • complete/ near-complete relief from pain • freedom from disruptions to daily routine
29 Acute Management- Pharmacologic Three major traditional pharmacologic classes: • anti-inflammatory agents • 5-HT1B/1D receptor agonists, • dopamine receptor antagonists. “Relatively” Newer agents • 5-HT1F receptor agonists (Ditans) • Calcitonin Gene-Related Peptide receptor antagonists
30 Pharmacologic management
31 Level A (established efficacy) if two high-quality studies support efficacy. Level B (probably effective) if one good-quality or two lower-quality studies support efficacy. Level C (possibly effective) if one lower-quality or two lowest-quality studies support efficacy. Level U (data inadequate or conflicting) if studies are conflicting or available studies are insufficient quality to contribute to knowledge.
32
33 Acute Management- Emergency • Parenteral administration of drugs such as dihydroergotamine and sumatriptan is approved by the FDA for the rapid relief of a migraine attack. • Peak plasma levels of dihydroergotamine are achieved • 3 min after IV dosing, • 30 min after IM dosing, • 45 min after SC dosing. • If an attack has not already peaked, SC or IM administration of 1 mg dihydroergotamine suffices for about 80–90% of patients. • Sumatriptan, 6 mg SC, is effective in 70–80% of patients. ∼
34 Acute management- Emergency • Drug absorption is impaired during migraine because of reduced gastrointestinal motility. • Delayed absorption occurs even in the absence of nausea and is related to the severity of the attack and not its duration. • When oral NSAIDs and/or triptan agents fail, the addition of a dopamine antagonist such as metoclopramide 10 mg should be considered to enhance gastric absorption. • Parenteral dopamine antagonists (e.g: chlorpromazine, prochlorperazine, metoclopramide) can also provide significant acute relief of migraine in combination with parenteral 5-HT1B/1D agonists. • A common IV protocol used for the treatment of severe migraine is the administration over 2 min of a mixture of 5 mg of prochlorperazine and 0.5 mg of dihydroergotamine.
35 Acute Management – Narcotic use • Narcotics are effective in the acute treatment of migraine eg : IV pethidine (50–100mg) in the emergency room. • This regimen is clearly suboptimal for patients with recurrent headache. • Narcotics do not treat the underlying headache mechanism; rather, they act to alter the pain sensation. • Narcotic addiction can greatly confuse the treatment of migraine. Narcotic craving and/or withdrawal can aggravate and accentuate migraine. • It is recommended that narcotic use in migraine be limited to patients with severe, but infrequent, headaches unresponsive to other pharmacologic approaches.
36 Acute Management: Triptan use Contraindications: • Uncontrolled hypertension • Ischaemic heart disease • Peripheral Artery Disease • History of stroke • Hemiplegic migraine • **Allow at least a 24-hour interval after Dihydroergotamine(DHE) use to use a triptan.
37 Acute Management: Triptan use • 7 oral triptans currently available • Varying onset of action and duration Memory Aid: R-E-S-Z-A-N-F Onset of Action Duration of Effect • Rizatriptan fastest shortest • Eletriptan • Sumatriptan • Zolmitriptan • Almotriptan • Naratriptan • Frovatriptan slowest longest
38 Acute Management: Triptan use • One dose for early/mild headache. • Dose may be repeated after 2 hours if headache recurs. (Max oral dose in 24 hours: 200mg) • Limit use to no more than 2-3 days / week to prevent medication overuse headaches. • May be used concurrently with NSAIDS/opioids and anti-emetics (dopamine antagonists) • If response less than desired for one triptan, a different triptan may be tried.
39 Medication overuse headache • Not a separate headache entity • Associated with Acute medications overuse (> 15 days/month for simple analgesics/NSAIDS, >10 days/month for triptans and opioids) • Propensity to aggravate headache frequency and induce a state of refractory daily or near-daily headache called medication- overuse headache.
40 Medication overuse headache Treatment: Breaking The Cycle • Stopping culprit medications versus gradual taper • Symptoms will worsen before they get better • Withdrawal symptoms: nervousness, restlessness, nausea, vomiting, insomnia, constipation (may last 2 to 10 days or several weeks) • May require admission • Bridging therapy / emergency parenteral treatment • Initiating prophylactic therapy Prevention • Use of non-pharmacological therapies for acute attacks • Limiting use of acute therapies to no more than 2-3 days per week.
41 Prophylactic Management Preventive therapies are among the most powerful tools available to improve the well-being of people with migraine. • reduction in attack frequency • reduce the severity or duration of headache attacks • reduce the need for acute treatment • improve efficacy of acute treatments • reduced disability • improved quality of life • A reduction in headache frequency of 50% or more is considered a good response to treatment.
42 Prophylactic management • Prior to development of Calcitonin Gene-Related Peptide (CGRP) monoclonal antibodies, only one medication (methysergide: semi-synthetic ergot alkaloid, 5HT2 antagonist, 5HT1 agonist) had been developed specifically for migraine prevention. • Methysergide withdrawn o/a fibrosis(retroperitoneal, pleural, subendocardial) and cardiac valve dysfunction. • Migraine prevention is therefore a secondary/off-label indication for most drugs currently in use as oral preventive agents. • Many such medications are efficacious as migraine preventives.
43 Prophylactic management- indications Two severe or disabling or four less disabling migraine attacks per month Acute migraine treatment ineffective or contraindicated Medication-overuse headache present Highly disabling migraine attacks (e.g., hemiplegic migraine or migraine with brainstem aura) Patient preference
44 Prophylactic Management – AHS/AAN 2021 • Level A (established as effective) if two high-quality studies support efficacy. • Level B (probably effective) if one good-quality or two lower-quality studies. • support efficacy, Level C (possibly effective) if one lower-quality or two lowest-quality studies support efficacy. • Level U (data inadequate or conflicting) if studies are conflicting or available studies are insufficient quality to contribute to knowledge.
45 Prophylactic Management – Drug classes (Memory Aid: A-B-C0N)
46 Prophylactic management
47 Prophylactic Management SOURCE: CONTINUUM (MINNEAP MINN) 2021;27(3, HEADACHE):613–632
48 Prophylactic medications: choices based on side effects, contraindications, comorbidities
49 Prophylactic medications: choices based on side effects, contraindications, comorbidities
50 Prophylactic medications: choices based on side effects, contraindications, comorbidities
51 Prophylactic management • The probability of success with any one of the antimigraine drugs is 50–75%. • Many patients are managed adequately with low-dose amitriptyline, propranolol, topiramate, gabapentin, or valproate. • Once effective stabilization is achieved, the drug is continued for 6 months and ∼ then slowly tapered to assess the continued need. • Many patients can discontinue medication and experience fewer and milder attacks with long periods of pain freedom.
52 Other treatment Modalities • Neuromodulation (acute) - electrical trigeminal nerve stimulation, - noninvasive vagus nerve stimulation, - single-pulse transcranial magnetic stimulation • Biobehavioral therapy - cognitive behavioral therapy, - biofeedback - relaxation therapies - mindfulness-based therapies, - acceptance and commitment therapy Cephaly device (transcutaneous supraorbital nerve stimulation)
53 Other treatment Modalities
54 Therapies under investigation • Adenosine receptors • Delta opioid receptors • Potassium channel modulators • Sodium channel modulators • Peptide targets : PACAP, Amylin
55 Migraine in Children: Modified ICHD-3 criteria Migraine without Aura • Headache duration: headache attacks lasting 2 to 72 hours (when untreated or unsuccessfully treated) • Headache location: can be unilateral or bilateral • Associated features: photophobia and phonophobia can be inferred from behavior
56 Migraine in Children May present as: • colic in infants: • Recurrent episodes of irritability, fussing, or crying from birth to 4 months of age • No concern for failure to thrive • Crying episodes • More than 3 times a week • For 3 or more hours per day • For at least 3 weeks • Cyclical vomiting • Abdominal migraine
57 Migraine in Children Practice Guidelines for preventive and acute treatment of migraine in children. American Academy of Neurology in Practical Neurology: Migraine in Children. May 2019
58 Migraine in children Hotop A, Ferguson M, Ask the PharmD: What are the recommendations for preventing and treating pediatric migraine? Pract Pain Manag. 2020;20(2)
59 Migraine in Pregnancy • Approximately one half to three-fourths of female migraineurs experience improvement in migraine with a significant reduction in the frequency and intensity of their attacks during the second and third trimester of pregnancy. • Women who have migraines with aura are at greater risk for having more frequent migraines during pregnancy. • Most of the recommended drugs for migraine prophylaxis are FDA pregnancy category C, D or even X as there are no specific clinical trials evaluating drug treatment of migraine during pregnancy and breastfeeding. • Nonpharmacologic options must be first line before drug therapy.
60 • Category A Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters). • Category B Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women. • Category C Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. • Category D There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. • Category X Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks
61 Migraine in Pregnancy Acute/Abortive Therapy: • Acetaminophen safe in all trimesters • NSAIDs may be used ONLY in the second trimester • Triptans are category C Preventive Therapy: • Consider prophylactic medication when the benefit of migraine prophylaxis for the mother and fetus is determined to be significantly higher than the risk associated with using prophylactic medications.
62 Contraindicated medications in Pregnancy • Calcitonin Gene Related Peptide(CGRP) monoclonal antibodies • Flunarizine • Topiramate • sodium valproate • zonisamide • MIG-99(extract of the herb feverfew).
63 Summary • Migraine can be modified and controlled by lifestyle adjustments and medications. it cannot be eradicated. • Pharmacologic treatment is individualized! One size does NOT fit all. • It is recommended that narcotic use in migraine be limited to patients with severe, but infrequent, headaches unresponsive to other pharmacologic approaches. • Except in women with migraine with aura on oral estrogens or combined oral contraceptives, migraine is not associated with serious or life-threatening illnesses. (migraine with aura : 2-3-fold increase in strokes). • Women of child-bearing age should be counselled about medications with teratogenic side effects and appropriate contraceptives. • Prophylactic medications reduce frequency and severity of migraine • Assessing comorbidities and migraine disability objectively helps improve quality of life of migraineurs.
64 THANK YOU!
65 QUIZ
66 Q 1. 1.Which of the following symptoms suggests a primary cause of headaches? a.Occurring regularly with menstrual cycle b.Photophobia c. Diplopia d.Worse on laying supine
67 Q 2. 1.The following substances are involved in migraine pathophysiology except: a.Acetylcholine b.Serotonin c. Estrogen d.Calcitonin Gene Related Peptide
68 Q 3. 1.Management of Migraine encompasses all the following but: a.Headache diary b.Regular exercise c. Trigger management d.Alcohol use
69 Q 4. 1.Which of the following is a migraine-specific abortive treatment? a.Paracetamol b.Sumatriptan c. Amitriptyline d.Caffeine
70 Q 5. 1.Which of the following describes preventive/prophylactic treatment for migraine? a.Should be taken at onset of migraine attack b.Should be taken daily for a specified period of time c. Should be taken as and when the headache gets worse d.Should be prescribed without considering comorbidities.
71 CASE DISCUSSIONS
72 Case 1 • 40-year-old female, A.B • Banker, married with 2 children • Asthmatic, BMI of 32 • Starting experiencing migraine as a teenager, worsened over past few years • Has headaches 4 days per week in the past 6 months • Takes a combination of acetaminophen/aspirin/caffeine for headaches • She has developed abdominal pains from regular use of the medication.
73 Case 1 • Left – sided headaches over the past 48hrs of 6/10 severity with nausea, photophobia and phonophobia. • She has been prescribed sumatriptan in the past by her primary care doctor. • Currently has to take maximum daily doses sumatriptan with little response. • She is still having headaches 4 days a week despite taking sumatriptan • She wants to be pain-free . • She feels guilty about “ignoring her children” as she stays away from them when her headaches are bad.
74 Case 1- Questions 1. How will you classify A.B’s migraines? 2. What are her comorbidities 3. What medications MUST you avoid? 4. Which medications will you consider for acute/abortive treatment? 5. Which medications will you consider for prophylactic/preventive treatment?
75 Case 1- Answers 1. Chronic migraine without aura 2. Asthma, obesity, NSAID-induced gastritis 3. Avoid beta blockers, NSAIDs , medications associated with weight gain. 4. Sumatriptan + dopamine antagonist; alternative triptan; alternative route of administration- sc /nasal; ergot derivatives. 5. Topiramate**; amitriptyline; valproic acid**; botulinum toxin Keep a headache diary, Look for triggers: avoid/modify, at onset of headaches DO NOT COMBINE TRIPTANS AND ERGOTS **Medications with teratogenic effects. Caution on effective contraception
76 Case 2 • 28-year-old female, EM, online marketer, works on her own schedule. • Single • BMI – 26 • On combined oral contraceptive pills. • Headache last night of 8/10 severity, right sided, associated with nausea and a tingling sensation running down her right arm in the first hour of the headache. • Had to turn off the television and room lights to enable her sleep.
77 Case 2 • Missed a planned evening out with her friends to celebrate a graduation. • Headache persists this morning at 6/10 severity. • Has had 3 similar episodes over the past 2 years relieved by ibuprofen. • Current episode is not responding to ibuprofen. • She denies any stressors but has been having poor sleep because of her neighbor’s dogs barking throughout the night the past week.
78 Case 2 1. How will you classify E.M’s migraines? 2. What are her comorbidities 3. What medications MUST you avoid? 4. Which medications will you consider for acute/abortive treatment? 5. Which medications will you consider for prophylactic/preventive treatment?
79 Case 2- Answers 1. Episodic migraine with aura (sensory) 2. Use of combined oral contraceptive pills (COCPs) in migraine with aura is associated with increased risk of stroke. 3. Switch COCPs to progestin-only or alternatives contraception e.g. IUD. 4. Her headaches are moderate to severe in intensity and infrequent. Find out when during the headache she takes ibuprofen. Should be taken at onset of pain. Alternatives: acetaminophen/aspirin/caffeine; opioids+ dopamine antagonist; triptans +/-NSAIDs +/-dopamine antagonists, ergots, gepants, ditans. 5. Not a candidate for Prophylaxis
80 Thank you for your participation! fadglover@gmail.com
81
82 NeurologyGhana neurosocietyghana neurosocietyghana@gmail.com

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Migraine - Diagnosis and Management.pptx

  • 1.
    1 Migraine: Diagnosis andManagement Dr. (Med) Freda Dodd-Glover Neurologist KBTH
  • 2.
    2 Outline • Primary Headachesoverview • Pathophysiology of migraine • Acute management • Prophylactic management • Case discussion
  • 3.
    3 What is aHeadache? • Pain or discomfort affecting any part of the head arising from pain- sensitive structures. • Pain located in the head, above the orbitomeatal line and/or nuchal ridge. Headache Facial Pain
  • 4.
    4 International Classification ofHeadache Disorders (ICHD-3) The ICHD-3 criteria defines three major categories of disorders: • primary headaches • secondary headaches • cranial neuralgias and facial pain
  • 5.
    5 Primary Headaches • Multipleentities causing episodic and chronic head pain/discomfort in the absence of underlying medical conditions, medications or traumatic injury. • Primary headache disorders include: • Migraine • Tension-Type Headache(TTH) • Trigeminal Autonomic Cephalalgias(TACS) • Other primary headache disorders
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    7 Infrequent episodic TensionType Headache (TTH) Diagnostic criteria: A. At least 10 episodes of headache occurring on <1 day/month on average (<12 days/year) and fulfilling criteria B-D B. Lasting from 30 minutes to 7 days C. At least two of the following four characteristics: A. bilateral location B. pressing or tightening (non-pulsating) quality C. mild or moderate intensity D. not aggravated by routine physical activity such as walking or climbing stairs D. Both of the following: A. no nausea or vomiting B. no more than one of photophobia or phonophobia E. Not better accounted for by another ICHD-3 diagnosis
  • 8.
    8 Frequent episodic TTH Diagnosticcriteria: A. At least 10 episodes of headache occurring on 1-14 days/month on average for >3 months (≥12 and <180 days/year) and fulfilling criteria B-D B. Lasting from 30 minutes to 7 days C. At least two of the following four characteristics: A. bilateral location B. pressing or tightening (non-pulsating) quality C. mild or moderate intensity D. not aggravated by routine physical activity such as walking or climbing stairs D. Both of the following: A. no nausea or vomiting B. no more than one of photophobia or phonophobia E. Not better accounted for by another ICHD-3 diagnosis.
  • 9.
    9 Chronic TTH Diagnostic criteria: A.Headache occurring on ≥15 days/month on average for >3 months (≥180 days/year), fulfilling criteria B-D B. Lasting hours to days, or unremitting C. At least two of the following four characteristics: A. bilateral location B. pressing or tightening (non-pulsating) quality C. mild or moderate intensity D. not aggravated by routine physical activity such as walking or climbing stairs D. Both of the following: A. no more than one of photophobia, phonophobia or mild nausea B. neither moderate or severe nausea nor vomiting E. Not better accounted for by another ICHD-3 diagnosis.
  • 10.
    10 Trigeminal Autonomic Cephalalgias(TACs) • A distinct set of headaches typified by shorter-lasting attacks of unilateral intense pain in the trigeminal distribution with ipsilateral cranial autonomic symptoms. • Cluster headaches • Paroxysmal hemicrania • Short-lasting unilateral neuralgiform headache attack (SUNHA) syndromes • Hemicrania continua
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    11 Trigeminal Autonomic Cephalalgias(TACs) • Characteristic Features: • Side-locked • V1 distribution predominantly • Shorter-lasting (with the exception of hemicrania continua) • Intense severity • Autonomic features overshadow nausea, photophobia, or phonophobia • Ptosis Forehead/facial sweating/flushing • Miosis Lacrimation • Periorbital oedema Aural fullness • Rhinorrhoea
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  • 13.
    13 What are Migraines? •A Migraine is a complex neurological disorder characterized by recurrent episodes of headaches mostly unilateral. • It may be associated with visual, sensory, motor, speech or brainstem symptoms— collectively known as aura. • Aura may arise most often before the head pain but that may occur during or afterward the headache.
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    15 What are Migraines? •Africa has an estimated fifty-six million people living with migraine. • World-wide prevalence is approximately 14-15 % • African studies report 5-10% • Male to female ratio of approximately 1:3
  • 16.
    16 Classification of Migraine •Migraine without aura (formerly, common migraine) • Probable migraine without aura • Migraine with aura (formerly, classic migraine) • Probable migraine with aura • Episodic migraine • Chronic migraine • Chronic migraine associated with analgesic overuse • Childhood periodic syndromes that may not be precursors to or associated with migraine - these syndromes include cyclic vomiting, abdominal migraine, and benign paroxysmal vertigo of childhood.
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    17 IHS Classification –ICHD 3:Migraine with aura The following criteria must be met: One or more visual, sensory, speech, motor, brainstem, or retinal symptoms, as well as at least 2 of the following 4 criteria: (1) at least 1 aura symptom spreading gradually over 5 or more minutes and/or 2 or more symptoms occurring in succession (2) each aura symptom lasting 5–60 minutes (3) at least 1 aura symptom being unilateral (4) the aura being accompanied by or followed shortly by headache (5) Not better accounted for by another ICHD-3 diagnosis.
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    18 IHS Classification –ICHD 3:Migraine without aura A. At least five attacks fulfilling criteria B–D B. Headache attacks lasting 4-72 hours (untreated or unsuccessfully treated) C. Headache has at least two of the following four characteristics: 1. unilateral location 2. pulsating quality 3. moderate or severe pain intensity 4. aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs) D. During headache at least one of the following: 1. nausea and/or vomiting 2. photophobia and phonophobia E. Not better accounted for by another ICHD-3 diagnosis. Memory Aid: 5-4-3-2-1 rule
  • 19.
    19 Migraine classification andvariants • Chronic migraine : > 15 days a month for 3 consecutive months with 8 of days fulfilling migraine criteria. • Episodic migraine: < 15 days a month • Status migrainosus: migraine lasting more than 72hours • Ophthalmoplegic migraine: 3rd nerve palsy, ptosis, ocular muscle paralysis . • Hemiplegic migraine. • Migraine equivalent (acephalgic): aura without migraine. Seen in persons with recurrent headaches, mostly older than 40.
  • 20.
    20 Pathophysiology The key structuresinvolved in migraine include: • the large intracranial vessels, dura mater and peripheral terminals of the trigeminal nerve that innervate these structures (the trigeminovascular complex) • the caudal portion of the trigeminal nucleus, which extends into the dorsal horns of the upper cervical spinal cord and receives input from the first and second cervical nerve roots (the trigeminocervical complex) • rostral pain-processing regions, such as the ventroposteromedial thalamus and the cortex . • the pain-modulatory systems in the brain that modulate input from trigeminal nociceptors at all levels of the pain-processing pathways.
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    22 Pathophysiology • Genetically susceptible/ hyperexcitable brain • ?Cortical spreading depression • Calcitonin Gene-Related Peptide • Substance P • Neurokinin A • Nitric Oxide • Serotonin • Cyclic adenosine monophosphate Oguzhan et al, Migraine and neuroinflammation, the inflammasome perspective, J. Headache Pain,22:55(2021)
  • 23.
    23 Acute Management • Oncea diagnosis of migraine has been established, it is important to assess the extent of a patient’s disease and disability. • The Migraine Disability Assessment Score (MIDAS) is a well-validated, easy-to-use tool. • Assessment and management of associated comorbidities is key. PHQ2, PHQ9, MSQ, SF-36
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    25 Acute Management –Patient education Patient education is an important aspect of migraine management. • It is helpful for patients to understand that migraine is an inherited tendency to headache • that migraine can be modified and controlled by lifestyle adjustments and medications • it cannot be eradicated; • except in women with migraine with aura on oral estrogens or combined oral contraceptives, migraine is not associated with serious or life-threatening illnesses. (migraine with aura : 2-3-fold increase in strokes) Curtis KM et al. Use of combined oral contraceptives among women with migraine and non-migrainous headaches. 2006;73:189-194. doi 10.1016/ j.contraception. 2005.08.009
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    26 Acute Management –Non-pharmacologic HEADACHE DIARY AVOID TRIGGERS HEALTHY DIET REGULAR EXERCISE REGULAR SLEEP PATTERNS AVOIDANCE OF EXCESS CAFFEINE AND ALCOHOL AVOIDANCE OF ACUTE CHANGES IN STRESS LEVELS
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    27 Acute Management- Pharmacologic •Judicious use of appropriate medications • The optimal regimen is individualized and depends on a number of factors: severity of the attack being key. • Mild migraine attacks can usually be managed by oral agents ( the average efficacy rate is 50–70%). • Severe migraine attacks may require parenteral therapy.
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    28 Acute Management- Pharmacologic Theideal acute/abortive medication should have/provide: • minimal / no adverse effects • Little requirement for repeat dosing • complete/ near-complete relief from pain • freedom from disruptions to daily routine
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    29 Acute Management- Pharmacologic Threemajor traditional pharmacologic classes: • anti-inflammatory agents • 5-HT1B/1D receptor agonists, • dopamine receptor antagonists. “Relatively” Newer agents • 5-HT1F receptor agonists (Ditans) • Calcitonin Gene-Related Peptide receptor antagonists
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    31 Level A (establishedefficacy) if two high-quality studies support efficacy. Level B (probably effective) if one good-quality or two lower-quality studies support efficacy. Level C (possibly effective) if one lower-quality or two lowest-quality studies support efficacy. Level U (data inadequate or conflicting) if studies are conflicting or available studies are insufficient quality to contribute to knowledge.
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    33 Acute Management- Emergency •Parenteral administration of drugs such as dihydroergotamine and sumatriptan is approved by the FDA for the rapid relief of a migraine attack. • Peak plasma levels of dihydroergotamine are achieved • 3 min after IV dosing, • 30 min after IM dosing, • 45 min after SC dosing. • If an attack has not already peaked, SC or IM administration of 1 mg dihydroergotamine suffices for about 80–90% of patients. • Sumatriptan, 6 mg SC, is effective in 70–80% of patients. ∼
  • 34.
    34 Acute management- Emergency •Drug absorption is impaired during migraine because of reduced gastrointestinal motility. • Delayed absorption occurs even in the absence of nausea and is related to the severity of the attack and not its duration. • When oral NSAIDs and/or triptan agents fail, the addition of a dopamine antagonist such as metoclopramide 10 mg should be considered to enhance gastric absorption. • Parenteral dopamine antagonists (e.g: chlorpromazine, prochlorperazine, metoclopramide) can also provide significant acute relief of migraine in combination with parenteral 5-HT1B/1D agonists. • A common IV protocol used for the treatment of severe migraine is the administration over 2 min of a mixture of 5 mg of prochlorperazine and 0.5 mg of dihydroergotamine.
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    35 Acute Management –Narcotic use • Narcotics are effective in the acute treatment of migraine eg : IV pethidine (50–100mg) in the emergency room. • This regimen is clearly suboptimal for patients with recurrent headache. • Narcotics do not treat the underlying headache mechanism; rather, they act to alter the pain sensation. • Narcotic addiction can greatly confuse the treatment of migraine. Narcotic craving and/or withdrawal can aggravate and accentuate migraine. • It is recommended that narcotic use in migraine be limited to patients with severe, but infrequent, headaches unresponsive to other pharmacologic approaches.
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    36 Acute Management: Triptanuse Contraindications: • Uncontrolled hypertension • Ischaemic heart disease • Peripheral Artery Disease • History of stroke • Hemiplegic migraine • **Allow at least a 24-hour interval after Dihydroergotamine(DHE) use to use a triptan.
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    37 Acute Management: Triptanuse • 7 oral triptans currently available • Varying onset of action and duration Memory Aid: R-E-S-Z-A-N-F Onset of Action Duration of Effect • Rizatriptan fastest shortest • Eletriptan • Sumatriptan • Zolmitriptan • Almotriptan • Naratriptan • Frovatriptan slowest longest
  • 38.
    38 Acute Management: Triptanuse • One dose for early/mild headache. • Dose may be repeated after 2 hours if headache recurs. (Max oral dose in 24 hours: 200mg) • Limit use to no more than 2-3 days / week to prevent medication overuse headaches. • May be used concurrently with NSAIDS/opioids and anti-emetics (dopamine antagonists) • If response less than desired for one triptan, a different triptan may be tried.
  • 39.
    39 Medication overuse headache •Not a separate headache entity • Associated with Acute medications overuse (> 15 days/month for simple analgesics/NSAIDS, >10 days/month for triptans and opioids) • Propensity to aggravate headache frequency and induce a state of refractory daily or near-daily headache called medication- overuse headache.
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    40 Medication overuse headache Treatment:Breaking The Cycle • Stopping culprit medications versus gradual taper • Symptoms will worsen before they get better • Withdrawal symptoms: nervousness, restlessness, nausea, vomiting, insomnia, constipation (may last 2 to 10 days or several weeks) • May require admission • Bridging therapy / emergency parenteral treatment • Initiating prophylactic therapy Prevention • Use of non-pharmacological therapies for acute attacks • Limiting use of acute therapies to no more than 2-3 days per week.
  • 41.
    41 Prophylactic Management Preventive therapiesare among the most powerful tools available to improve the well-being of people with migraine. • reduction in attack frequency • reduce the severity or duration of headache attacks • reduce the need for acute treatment • improve efficacy of acute treatments • reduced disability • improved quality of life • A reduction in headache frequency of 50% or more is considered a good response to treatment.
  • 42.
    42 Prophylactic management • Priorto development of Calcitonin Gene-Related Peptide (CGRP) monoclonal antibodies, only one medication (methysergide: semi-synthetic ergot alkaloid, 5HT2 antagonist, 5HT1 agonist) had been developed specifically for migraine prevention. • Methysergide withdrawn o/a fibrosis(retroperitoneal, pleural, subendocardial) and cardiac valve dysfunction. • Migraine prevention is therefore a secondary/off-label indication for most drugs currently in use as oral preventive agents. • Many such medications are efficacious as migraine preventives.
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    43 Prophylactic management- indications Twosevere or disabling or four less disabling migraine attacks per month Acute migraine treatment ineffective or contraindicated Medication-overuse headache present Highly disabling migraine attacks (e.g., hemiplegic migraine or migraine with brainstem aura) Patient preference
  • 44.
    44 Prophylactic Management –AHS/AAN 2021 • Level A (established as effective) if two high-quality studies support efficacy. • Level B (probably effective) if one good-quality or two lower-quality studies. • support efficacy, Level C (possibly effective) if one lower-quality or two lowest-quality studies support efficacy. • Level U (data inadequate or conflicting) if studies are conflicting or available studies are insufficient quality to contribute to knowledge.
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    45 Prophylactic Management –Drug classes (Memory Aid: A-B-C0N)
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    47 Prophylactic Management SOURCE: CONTINUUM(MINNEAP MINN) 2021;27(3, HEADACHE):613–632
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    48 Prophylactic medications: choicesbased on side effects, contraindications, comorbidities
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    49 Prophylactic medications: choicesbased on side effects, contraindications, comorbidities
  • 50.
    50 Prophylactic medications: choicesbased on side effects, contraindications, comorbidities
  • 51.
    51 Prophylactic management • Theprobability of success with any one of the antimigraine drugs is 50–75%. • Many patients are managed adequately with low-dose amitriptyline, propranolol, topiramate, gabapentin, or valproate. • Once effective stabilization is achieved, the drug is continued for 6 months and ∼ then slowly tapered to assess the continued need. • Many patients can discontinue medication and experience fewer and milder attacks with long periods of pain freedom.
  • 52.
    52 Other treatment Modalities •Neuromodulation (acute) - electrical trigeminal nerve stimulation, - noninvasive vagus nerve stimulation, - single-pulse transcranial magnetic stimulation • Biobehavioral therapy - cognitive behavioral therapy, - biofeedback - relaxation therapies - mindfulness-based therapies, - acceptance and commitment therapy Cephaly device (transcutaneous supraorbital nerve stimulation)
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  • 54.
    54 Therapies under investigation •Adenosine receptors • Delta opioid receptors • Potassium channel modulators • Sodium channel modulators • Peptide targets : PACAP, Amylin
  • 55.
    55 Migraine in Children:Modified ICHD-3 criteria Migraine without Aura • Headache duration: headache attacks lasting 2 to 72 hours (when untreated or unsuccessfully treated) • Headache location: can be unilateral or bilateral • Associated features: photophobia and phonophobia can be inferred from behavior
  • 56.
    56 Migraine in Children Maypresent as: • colic in infants: • Recurrent episodes of irritability, fussing, or crying from birth to 4 months of age • No concern for failure to thrive • Crying episodes • More than 3 times a week • For 3 or more hours per day • For at least 3 weeks • Cyclical vomiting • Abdominal migraine
  • 57.
    57 Migraine in Children PracticeGuidelines for preventive and acute treatment of migraine in children. American Academy of Neurology in Practical Neurology: Migraine in Children. May 2019
  • 58.
    58 Migraine in children HotopA, Ferguson M, Ask the PharmD: What are the recommendations for preventing and treating pediatric migraine? Pract Pain Manag. 2020;20(2)
  • 59.
    59 Migraine in Pregnancy •Approximately one half to three-fourths of female migraineurs experience improvement in migraine with a significant reduction in the frequency and intensity of their attacks during the second and third trimester of pregnancy. • Women who have migraines with aura are at greater risk for having more frequent migraines during pregnancy. • Most of the recommended drugs for migraine prophylaxis are FDA pregnancy category C, D or even X as there are no specific clinical trials evaluating drug treatment of migraine during pregnancy and breastfeeding. • Nonpharmacologic options must be first line before drug therapy.
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    60 • Category A Adequateand well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters). • Category B Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women. • Category C Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. • Category D There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. • Category X Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks
  • 61.
    61 Migraine in Pregnancy Acute/AbortiveTherapy: • Acetaminophen safe in all trimesters • NSAIDs may be used ONLY in the second trimester • Triptans are category C Preventive Therapy: • Consider prophylactic medication when the benefit of migraine prophylaxis for the mother and fetus is determined to be significantly higher than the risk associated with using prophylactic medications.
  • 62.
    62 Contraindicated medications inPregnancy • Calcitonin Gene Related Peptide(CGRP) monoclonal antibodies • Flunarizine • Topiramate • sodium valproate • zonisamide • MIG-99(extract of the herb feverfew).
  • 63.
    63 Summary • Migraine canbe modified and controlled by lifestyle adjustments and medications. it cannot be eradicated. • Pharmacologic treatment is individualized! One size does NOT fit all. • It is recommended that narcotic use in migraine be limited to patients with severe, but infrequent, headaches unresponsive to other pharmacologic approaches. • Except in women with migraine with aura on oral estrogens or combined oral contraceptives, migraine is not associated with serious or life-threatening illnesses. (migraine with aura : 2-3-fold increase in strokes). • Women of child-bearing age should be counselled about medications with teratogenic side effects and appropriate contraceptives. • Prophylactic medications reduce frequency and severity of migraine • Assessing comorbidities and migraine disability objectively helps improve quality of life of migraineurs.
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    66 Q 1. 1.Which ofthe following symptoms suggests a primary cause of headaches? a.Occurring regularly with menstrual cycle b.Photophobia c. Diplopia d.Worse on laying supine
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    67 Q 2. 1.The followingsubstances are involved in migraine pathophysiology except: a.Acetylcholine b.Serotonin c. Estrogen d.Calcitonin Gene Related Peptide
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    68 Q 3. 1.Management ofMigraine encompasses all the following but: a.Headache diary b.Regular exercise c. Trigger management d.Alcohol use
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    69 Q 4. 1.Which ofthe following is a migraine-specific abortive treatment? a.Paracetamol b.Sumatriptan c. Amitriptyline d.Caffeine
  • 70.
    70 Q 5. 1.Which ofthe following describes preventive/prophylactic treatment for migraine? a.Should be taken at onset of migraine attack b.Should be taken daily for a specified period of time c. Should be taken as and when the headache gets worse d.Should be prescribed without considering comorbidities.
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    72 Case 1 • 40-year-oldfemale, A.B • Banker, married with 2 children • Asthmatic, BMI of 32 • Starting experiencing migraine as a teenager, worsened over past few years • Has headaches 4 days per week in the past 6 months • Takes a combination of acetaminophen/aspirin/caffeine for headaches • She has developed abdominal pains from regular use of the medication.
  • 73.
    73 Case 1 • Left– sided headaches over the past 48hrs of 6/10 severity with nausea, photophobia and phonophobia. • She has been prescribed sumatriptan in the past by her primary care doctor. • Currently has to take maximum daily doses sumatriptan with little response. • She is still having headaches 4 days a week despite taking sumatriptan • She wants to be pain-free . • She feels guilty about “ignoring her children” as she stays away from them when her headaches are bad.
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    74 Case 1- Questions 1.How will you classify A.B’s migraines? 2. What are her comorbidities 3. What medications MUST you avoid? 4. Which medications will you consider for acute/abortive treatment? 5. Which medications will you consider for prophylactic/preventive treatment?
  • 75.
    75 Case 1- Answers 1.Chronic migraine without aura 2. Asthma, obesity, NSAID-induced gastritis 3. Avoid beta blockers, NSAIDs , medications associated with weight gain. 4. Sumatriptan + dopamine antagonist; alternative triptan; alternative route of administration- sc /nasal; ergot derivatives. 5. Topiramate**; amitriptyline; valproic acid**; botulinum toxin Keep a headache diary, Look for triggers: avoid/modify, at onset of headaches DO NOT COMBINE TRIPTANS AND ERGOTS **Medications with teratogenic effects. Caution on effective contraception
  • 76.
    76 Case 2 • 28-year-oldfemale, EM, online marketer, works on her own schedule. • Single • BMI – 26 • On combined oral contraceptive pills. • Headache last night of 8/10 severity, right sided, associated with nausea and a tingling sensation running down her right arm in the first hour of the headache. • Had to turn off the television and room lights to enable her sleep.
  • 77.
    77 Case 2 • Misseda planned evening out with her friends to celebrate a graduation. • Headache persists this morning at 6/10 severity. • Has had 3 similar episodes over the past 2 years relieved by ibuprofen. • Current episode is not responding to ibuprofen. • She denies any stressors but has been having poor sleep because of her neighbor’s dogs barking throughout the night the past week.
  • 78.
    78 Case 2 1. Howwill you classify E.M’s migraines? 2. What are her comorbidities 3. What medications MUST you avoid? 4. Which medications will you consider for acute/abortive treatment? 5. Which medications will you consider for prophylactic/preventive treatment?
  • 79.
    79 Case 2- Answers 1.Episodic migraine with aura (sensory) 2. Use of combined oral contraceptive pills (COCPs) in migraine with aura is associated with increased risk of stroke. 3. Switch COCPs to progestin-only or alternatives contraception e.g. IUD. 4. Her headaches are moderate to severe in intensity and infrequent. Find out when during the headache she takes ibuprofen. Should be taken at onset of pain. Alternatives: acetaminophen/aspirin/caffeine; opioids+ dopamine antagonist; triptans +/-NSAIDs +/-dopamine antagonists, ergots, gepants, ditans. 5. Not a candidate for Prophylaxis
  • 80.
    80 Thank you foryour participation! fadglover@gmail.com
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Editor's Notes

  • #3 It’s a common and often cardinal manifestation of a myriad of diseases, and may be a disease unto itself, Pain referred to the forehead, orbits, temples or scalp. Does not usually cover pain isolated to the face or neck.
  • #5 According to ichd 1ST 3 The most common
  • #6 Systemic-hpt, immunosupression P-Papilloedema, post traumatic,
  • #10 As the name would imply
  • #22 CGRP (Intrinsically involved in migraine pathogenesis, Belongs to calcitonin family, Expressed in subset of small neurons in vagus, trigeminal and dorsal root ganglion)
  • #58 CHAMP study – amitriptyline, topiramate and placebo. Terminated early for futility o/a similar outcomes at 6 months