1. NEW TRENDS IN HEADACHE AND MIGRAINE TREATMENT
Kathie Teta, RN, CPNP
PANDA Neurology
Atlanta, Georgia

2. OBJECTIVES
1. Define concepts of a migraine headache and migraine variants from other headache types in the pediatric/adolescent population
2. Discuss pathophysiology of migraine headaches
3. Discuss indications for diagnostic testing for migraines
4. Identify appropriate treatment strategies for acute migraine management

3. OBJECTIVES
5. List types of preventive versus abortive treatments for headaches and migraines
6. Discuss when referrals to pediatric neurology are needed for further evaluation and management

4. “So you think YOU’VE got a Headache?!”

5. Migraine without aura Moderate to severe pain:
Unilateral/bilateral
Throbbing/squeezing
2 of 3 cardinal features:
Photophobia
Inability to function
Nausea/vomiting
Exertional worsening
Sound sensitivity
Duration of 4 to 72 hours

6. Migraine with aura Similar to migraines without aura
20 – 30 % migraneurs have aura (99% of these have visual auras)
Warning symptoms may include:
Visual disturbances
Numbness in arm or leg
Difficulty speaking
Warning symptoms last 5 – 6 minutes and typically are followed by headache pain

8. Chronic migraine Headaches occurring on or > 15 days per month
Current or prior diagnosis of migraine
Lasting on average > 4 hours per day

9. Risk factors for chronic migraine
Obesity
Lowered social economic status
Stressful events
Snoring
Overuse of caffeine
Depression
Anxiety

10. Medication overuse headache
Use of over-the-counter medications more than 1 – 2 times per week
Overuse of abortive prescription medications

11. Migraine Variants Abdominal migraines Benign paroxysmal vertigo
Diffuse abdominal pain, sometimes associated with headache
Can last 1 – 72 hours
Benign paroxysmal vertigo
Usually occurs in toddlers and young children
Appear off balance, may refuse to walk
Can last minutes to hours
Cyclic vomiting
Occurs in school-age children
Forceful, frequent vomiting lasting 1 hour to 5 days

12. Incidence of migraine 4 -5% of young children 5 – 6% in preadolescents
Increases in adolescence
18% women, 6% men as adults

13. AGE- AND GENDER-SPECIFIC PREVALENCE OF MIGRAINE
Lipton RB, Stewart WF. Neurology
Migraine Prevalence (%)
In both males and females, the prevalence distribution of migraine is an inverted U-shape curve. Prevalence rises through early adult life and then falls after middle life. The second important point to emphasize on this slide is that, at all post-pubertal ages, migraine is substantially more common in women than in men.
The prevalence of migraine varies as a function of age. Migraine is a disorder that is most prevalent between the ages of 25 and 55. Part of the reason the condition has such a big impact in the workplace is that it affects people during their peak productive years.
At pre-pubertal ages, the rate of onset for migraine is actually a little bit higher in boys than in girls, but at all post-pubertal ages, the incidence is higher in girls than in boys. The incidence of migraines without aura peaks around age 12 in boys and age 15 in girls. Although half of all migraine onsets begin before the age of 20, migraine can begin at age 1.
Lipton RB, Stewart WF. Migraine in the United States: a review of epidemiology and health care use. Neurology.1993;43(suppl 3):S6-S10.
Stewart WF, Linet MS, Celantano DD, VanNatta M, Ziegler D. Age- and sex-specific incidence rates of migraine with and without visual aura. Am J of Epidemiology. 1991;134:

14. PATHOPHYSIOLOGY OF MIGRAINE
Migraine has plagued mankind since the early ages. In the last century there was considerable debate regarding the pathogenesis of migraine, which has focused on two theories. Wolff’s vasogenic theory considers migraine to be the result of changes in the cranial vessels. Alternatively, the neurogenic theory classifies migraine as a brain disorder in which neuronal dysfunction causes neurologic symptoms and vascular changes.
The optimal assessment and management of patients with migraine requires an understanding of the basic anatomy and physiology of the cranial circulation. The trigeminovascular system is a therapeutic target for attack treatment to arrest the final common pathway for expression of neurovascular head pain. However, the brain is the essential key to the disorder, both in terms of its origin, and ultimate understanding and control.

15. The Migraine Process: Activation of Nerves and Blood Vessels
For many years migraine was thought to be a vascular disorder, a process involving constriction of cranial blood vessels followed by reflex dilation. Researchers have since demonstrated that migraine involves more than blood vessels. It also involves trigeminal nerve endings that surround the blood vessels, inflammatory neuropeptides released from the trigeminal nerve endings and the brain stem. Calcitonin Gene-Related Peptide (CGRP), one important inflammatory mediator, is a neuropeptide released from trigeminal nerve endings during migraine. It is a potent vasodilator and has been linked to the pain in migraine.
Triptans are believed to interrupt the migraine process by stimulating 5HT1b receptors on cranial blood vessels to reduce the pain-inducing vasodilation and by stimulating the 5HT1d receptors on trigeminal nerve endings that surround the blood vessels to block the release of neuropeptides (e.g., CGRP) that cause further vasodilation and neurogenic inflammation.

16. One Nerve Pathway, Multiple Symptoms, Multiple Manifestations of Migraine

17. Genetic basis
Strong family history of migraines

18. Sleep deprivation or excess Environmental factors
MIGRAINE TRIGGERS
Diet
Physical exertion
Hormonal changes
Head trauma
Stress and anxiety
More than in any other headache disorder, migraineurs identify triggers. Dietary factors are frequently reported triggers, although few have been scientifically validated. While their impact is probably not great for the population, they could be for the individual. Oversleeping and sleep deprivation are commonly recognized triggers. Patients should maintain a routine bedtime and avoid sleeping in.
Hormonal headaches are triggered by variations in female estrogen level and possibly other hormonal factors. Noise, bright lights, and fumes are commonly identified migraine triggers. Physical exertion can cause headache with subtype exercise-induced migraine. Stress is the trigger most commonly listed by patients.
Sleep deprivation or excess
Environmental factors

19. Avoid Triggers Foods: Chronobiology: sleep disturbance
MSG, peanuts, chocolate, caffeine, cheese, nitrites
Chronobiology: sleep disturbance
Environmental: weather changes
Stress: school, family changes, moving
Physical: sports activities, heat
Letdown: weekends, vacation, end of projects

20. Differential diagnoses
Sinus infection
Nasal congestion
Nasal drainage
Pain over frontal or maxillary sinuses

21. Cranial Parasympathetic Activation May Explain “Sinus-Like” Symptoms in Migraine
The sinus cavities and tear ducts are innervated by cranial parasympathetic nerves. When activated, symptoms like lacrimation, rhinnorhea and congestion can occur. Because activation of the TNC in migraine can result in reflex activation of the cranial parasympathetic nervous system, a sinus-like presentation of migraine can occur.

22. Tension headache Dull, aching, nonthrobbing
Not associated with vomiting
Pain or discomfort in the head, scalp, or neck, usually associated with muscle tightness in these areas

23. Differential diagnoses
Brain lesion
Subarachnoid hemorrhage
Meningoencephalitis
Acute hydrocephalus
Chiari I malformation
Pseudotumor Cerebri

24. Chiari I malformation

26. Diagnostic testing Imaging studies Blood tests Lumbar puncture
CT vs MRI
If new onset severe headache
Hard to treat or progressive headaches
AM headaches/AM vomiting
Focal features on examination
Poor family history
Blood tests
R/O causes for fatigue, possible infection, thyroid abnormalities
Lumbar puncture
If concerns with papilledema

27. Treatment for migraines
Lifestyle modifications
Diet
Increase water
Decrease caffeine
Decrease nitrates
Sleep
Dealing with stress
Decrease use of over-the-counter medications
Phamacologic therapy

29. Goals of Acute treatment
Functional response (ability to return to normal activities)
Consistent and quick onset
Prevent headache recurrence
Well tolerated

30. Mechanisms of action of acute anti-migraine drugs
Cranial vasoconstriction
Peripheral neuronal inhibition
Modulates activity in neuroreceptors at multiple sites along trigeminal pathway

31. Acute Treatment Options for Migraines
Nonspecific: (for mild/moderate pain)
NSAIDs
Combination analgesics
Opioids
Neuroleptics/antiemetics
corticosteroids
Specific (for severe pain)
Triptans
Ergotamine (DHE)

32. Routes of Administration
Oral therapies: most medications
Nasal sprays: sumatriptan, zolmitriptan, DHE
Injectable: (SQ, IM, IV) sumatriptan, DHE, injectable NSAIDs, opioids, neuroleptics
Suppositories: antiemetics, ergots, opioids

33. Triptan use
Imitrex (sumatriptan) and Maxalt (rizatriptan) – usually tier 1 on insurance formularies
Use at early onset migraine
May repeat 1X in 2 hours if needed
Maximum 2 doses in 24 hours
Should be used no more than 2 times per week

34. GOALS OF PREVENTIVE TREATMENT
Decrease attack frequency (by 50%) duration and intensity
Improve responsiveness to acute treatment
Improve function and decrease disability

35. GUIDELINE: WHEN TO USE PREVENTIVE MEDICATIONS
Migraine significantly interferes with patient’s daily routine, despite acute Rx
Acute medications contraindicated, ineffective, intolerable AEs or overused
Frequent headache (>1 - 2 attacks per week)
Uncommon migraine conditions
Patient preference

36. Preventive Medication Groups
Anticonvulsants
Valproate
Gabapentin
Topiramate
Zonegran
Neurontin
Antidepressants
TCAs
SSRIs
MAOIs
ß-adrenergic blockers
Propranolol
Calcium channel antagonists
Verapamil
Others
NSAIDs
Riboflavin
Magnesium
Petadolex
Feverfew
Preventive Medication Groups
There are several different classes of medication that are used as preventive therapies for migraine. The selection of one of these classes of medications can be determined by careful and complete review of possible coexisting conditions, risk factors, and patient preferences.

37. Tailor Therapy Appropriately to Comorbid Conditions
Avoid
Asthma
Depression Athlete
b-Blocker
Epilepsy
Arrhythmia
Bipolar
Tricyclic Antidepressant
TCA
Peptic Ulcer Disease
NSAIDs
Peripheral Vascular Disease
Ergots/Triptans
Adapted from Silberstein S. Headache in Clinical Practice. 2002:93. 56

38. Preventive Treatment Options
First line preventive treatment
Corticosteroids – for daily headaches that have been occurring for several weeks
Topamax (topiramate) - consider weight/eating habits
Amitriptyline – consider mood, sleep difficulties
Cyproheptadine – consider for young children
Calcium channel blockers/beta blockers – consider if mildly hypertensive

39. Nonpharmacologic Therapies Tested in Clinical Trials
Behavioral Treatments
Relaxation training*
Hypnotherapy
Thermal biofeedback training*
Electromyographic biofeedback therapy*
Cognitive/behavioral management therapy*
Physical Treatments
Acupuncture
Transcutaneous electrical nerve stimulation (TENS)
Occlusal adjustment
Cervical manipulation
Nonpharmacologic Therapies Tested in Clinical Trials
There are many nonpharmacologic treatments used as preventive therapies for migraine; those tested in clinical trials’ settings are listed herein. Most of the treatments can be classified as either behavioral or physical therapies. Relaxation therapy, thermal biofeedback, EMG biofeedback, and cognitive/behavioral management therapy have all reported efficacy as preventive therapy for migraine.
Campbell JK, Penzien DB, Wall EM. Evidence-based Guidelines for Migraine Headache: Behavioral and Physical Treatments. [American Academy of Neurology Web Site]. April 23, Available at: http// Accessed September 1, 2000.
*Proven effective in clinical trials
Adapted from US Headache Consortium Headache Guidelines

40. Candidates for Nonpharmacologic Therapy
Patient’s preference
Poor tolerance to drug therapy
Contraindications to drug therapy
Insufficient response to medication alone
Pregnancy
Acute medication overuse
High stress
Candidates for Nonpharmacologic Therapy
Behavioral and physical treatments for migraine are useful not only for patients who prefer nonpharmacologic therapies but also for all patients with migraine. Nonpharmacologic therapies fall into three categories:
Relaxation training
Biofeedback therapy, and
Stress management training (also called cognitive behavioral training)
The goals of nonpharmacologic therapies are to prevent migraine attacks and reduce frequency, severity and disability rather than relieve acute attacks. Therefore, these strategies are generally used in combination with acute treatment.
Many patients try nonpharmacologic therapy as an adjunct to other pharmacologic therapy (eg, stress management and biofeedback).
In certain patient populations, nonpharmacologic therapy is preferred because of the risk of adverse events associated with some medications or frequency/intensity of their migraine attacks.
Campbell JK, Penzien DB, Wall EM. Evidence-based Guidelines for Migraine Headache: Behavioral and Physical Treatments. [American Academy of Neurology Web Site]. April 23, Available at: http// Accessed September 1, 2000.
Adapted from US Headache Consortium Headache Guidelines

41. New Trends in Migraine Management
Botox injections
Nerve blocks
Trigger point injections
Nerve stimulator trials
Transcutaneous sumatriptan (battery powered)
Livodex – inhaled DHE

42. Referral to Pediatric Neurology
Refer children and adolescents with headaches if:
Poor response to acute treatment
Uncertainty of diagnosis
Unusual features
Co-morbidities
Need for preventive treatment
Concerns or alarming findings on examination