Clinical case. Clinical case 3/15/2018 OVERVIEW. Refractory headaches and update on novel treatment. Refractory headache.

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1 OVERVIEW Refractory headaches and update on novel treatment Definition of refractory headache Treatment approach Medications Neuromodulation In the pipeline Juliette Preston, MD OHSU Headache Center Refractory headache What does it mean? Unresponsiveness to treatment High frequency of headache Severe disability is present All of the above This is a 5- yo woman with migraine without aura since age 1, asthma, hypothyroidism who presented to the Headache Clinic with chronic daily headache. She recalls about - headaches per week until about years when her headaches became daily. There was no trauma or illness preceding the onset of daily headache Her headaches are located behind the eyes, in the forehead, and top of the head. The quality of the pain is throbbing. The intensity of the pain is moderate. Her headaches are associated with sensitivity to light, sound and fatigue. Her headaches are aggravated by movement (routine physical activity). She denies any unilateral conjunctival injection, lacrimation, rhinorrhea, ptosis, aural pressure or agitation/restlessness associated with her headaches. She also denies any visual aura, dysarthria, numbness, tingling or weakness in face, arm or leg associated with her headaches

2 She used Imitrex only for her most severe headache, one or twice per week. She tried Amitriptyline, Topamax, and Botox. Exam was normal. MRI brain done the previous year was normal. Does she have refractory migraine? 7 8 Toolbox to define refractory headache 1 st rule: make sure headaches meet criteria for primary headache disorder ( migraine in this case) nd rule: make sure to rule out medication overuse headache. rd rule: Adequate dose of prophylactic agents are used. th rule: Medication trial was done over an appropriate length of time. Medication overuse headache Headache present on >15 days/month. Regular overuse for > months of one or more drugs that can be taken for acute and/or symptomatic treatment of headache. Headaches have worsened 9 10 Medication overuse headache Using triptan, ergots, analgesics > 10 days per month. Using opioid > 8 days per month. Using Butalbital containing products > 5 days per month. For her neck pain, patient has been taking daily Excedrin. Not a refractory headache patient Bigal et al. Headache

3 Refractory headache toolbox Clinical Case Primary headache Rule out MOH Adequate dose of prophylactic agents are used Medication trial was done over an appropriate length of time. Tried Amitriptyline at 10 mg for months. Effective dose: mg daily (Couch et al. Headache. 010). Tried Topamax at 5 mg for weeks. Effective dose: mg ( target 100 mg) for months (Diener et al. Cephalgia. 007) 1 1 Atenolol: mg Nadolol :0-160 mg (fewer side effects than Propanolol) Propranolol: 0-0 mg ( short acting - times per day) Amitriptyline : mg ( start at 10 mg) Nortriptyline: mg ( start at 10 mg) Venlafaxine: 75-5 mg ( start at 7.5 mg) Valproate/divalproex: mg Topiramate: mg ( start at 5 mg) Clinical Case 5 yo woman- did not have refractory headache Medication overuse- treated with bridging therapy: Stop daily Excedrin 6-8 week of daily Meloxicam ( can use Aleve/Celebrex) Limit Sumatriptan to 10 days per month 17 18

4 Clinical Case After months, she returned to clinic, still with - headaches per week. Resume a preventative- Lisinopril 10 mg daily Lisinopril 5-0 mg daily Candesartan - mg daily (goal 16 mg ) ( Shrader et al. BMJ. 001) At months follow-up, only 1 mild headache per week Refractory headache toolbox Primary headache Rule out MOH Adequate dose of prophylactic agents are used Medication trial was done over an appropriate length of time. Neuromodulation For patients who do no want/tolerate medications ( and/or injections). Trigeminal nerve stimulation Vagal nerve stimulation 1

5 5 6 Trigeminal nerve stimulator Preventative: 0 min at night Abortive: 60 min Vagal nerve stimulator In 008, University of Oklahoma did a retrospective review of all of the patients in their VNS registry (N= ) and questionnaire about headache was sent. 10 patients met criteria for migraine headache 8/10 (80%) reported a 50% decrease in headache frequency in the first months after stimulator placement, sustained for the following months. ( Lenaerts et al. Cephalalgia 008) Pathophysiology of Migraine 1 Migraine pathophysiology: lessons from mouse models and human genetics Michel D Ferrari, Lancet Neurology, Volume 1, Issue 1, 015, Phase 1: Central Generator Deep nuclei in the brainstem-hyperexcitable Phase : Peripheral mechanism-trigeminal nerve fiber are activated. Neuropeptide are released into vessel wall (meningeal blood vessel) Causing sterile inflammation reaction (vasodilation, plasma extravasation, mast cell degranulation) Phase : Central again Trigeminal nucleus caudalis in lower brainstem Phase : Central Sensitization Ascending signal recruit more neurons ( causing allodynia, photophobia, and phonophobia) 9 x minutes stimulation 5-10 minutes apart ( times per day) 0 5

6 VNS and Migraine Migraine pathophysiology: lessons from mouse models and human genetics 1 VNS acts on the TNC via the Nucleus tractus solitarius Michel D Ferrari, Lancet Neurology, Volume 1, Issue 1, 015, OVERVIEW Conclusion: it is safe and may work when given time. May be considered for patients who can not tolerate drugs or drugs are contraindicated ( elderly, pregnant women and children) Definition of refractory headache Treatment approach Medications Neuromodulation In the pipeline 5 6 6

7 CGRP CGRP level are higher in migraineurs. During migraine attack, level of CGRP increase. Injecting CGRP triggers a migraine. Injecting antibody to CGRP or its receptor decrease migraine frequency Shuster, Nature Reviews, Summary Not every chronic/daily headache patient is a refractory headache patient. Consider all options including medication ( revisit if dose/length was not appropriate) Consider neuromodulation. By summer, we may be able to add monoclonal antibodies to our toolbox. Thank You 9 7