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MANAGING PRIMARY HEADACHES AN OVERVIEW FAYYAZ AHMED HULL & EAST YORKSHIRE HOSPITALS NHS TRUST.

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Presentation on theme: "MANAGING PRIMARY HEADACHES AN OVERVIEW FAYYAZ AHMED HULL & EAST YORKSHIRE HOSPITALS NHS TRUST."— Presentation transcript:

1 MANAGING PRIMARY HEADACHES AN OVERVIEW FAYYAZ AHMED HULL & EAST YORKSHIRE HOSPITALS NHS TRUST

2 LEARNING OUTCOME The Current management strategy for common primary headache disorders The Current management strategy for common primary headache disorders Appraisal of currently available treatments Appraisal of currently available treatments New treatments on the horizon New treatments on the horizon

3 Primary Headache Disorders: Frequency Classification Primary Headache disorders Secondary Headache disorders Paroxysmal Headache Attack Duration < 4 hours +/or Discrete episodes Long lasting Headache Daily or near daily headache Duration > 4 hours per day Chronic Migraine Chronic Tension- type headache New Daily Persistent headache Hemicrania Continua Adapted from Silberstein et al., Neurology (1996) 47: 871- With or without medication overuse Episodic Chronic

4 EPISODIC VERSUS CHRONIC EPISODIC EPISODIC MIGRAINE MIGRAINE TENSION HEADACHE TENSION HEADACHE CLUSTER HEADACHE CLUSTER HEADACHE CHRONIC CHRONIC CHRONIC MIGRAINE CHRONIC MIGRAINE CHRONIC TENSION TYPE HEADACHE CHRONIC TENSION TYPE HEADACHE MEDICATION OVERUSE HEADACHE MEDICATION OVERUSE HEADACHE CHRONIC CLUSTER HEADACHE CHRONIC CLUSTER HEADACHE

5 03/05/2015

6 Episodic Migraine; How to manage? Identify any obvious triggers Identify any obvious triggers Infrequent attacks Infrequent attacks Acute treatment only Acute treatment only Frequent attacks Frequent attacks Acute and Preventative treatments Acute and Preventative treatments

7 03/05/ High Percentage of Migraine Patients Report Triggers 76% to 95% of patients report triggers*,1 The mean number of triggers per patient is Stress has been shown to be even more important in chronic migraine than in episodic migraine StressHormonesNot Eating WeatherSleep Disturb. Perfume/ Odor Neck Pain LightsAlcoholSmokeSleeping Late HeatFood Percent of Patients Triggers 1. Kelman L Cephalalgia 2007;27:394– Radat F et al. Cephalalgia 2009;29:338–350. *Percentage of patients reporting depends on how the question is asked.

8 ACUTE TREATMENT OF MIGRAINE ATTACK Ergot (1868) Ergot (1868) Salicylic acid (1870) Salicylic acid (1870) Ergotamine Ergotamine Dihydroergotamine (DHE) Dihydroergotamine (DHE) Triptans in early 90’s ( working on 5 HT1 receptors ) Triptans in early 90’s ( working on 5 HT1 receptors ) Sumatriptan Sumatriptan Rizatriptan Rizatriptan Eletriptan Eletriptan Almotriptan Almotriptan Zolmitriptan Zolmitriptan Naratriptan Naratriptan Frovatriptan Frovatriptan

9 03/05/20159 Standard abortive therapy Standard abortive therapy Migraine; How to manage?

10 Acute Rx: Key Message Avoid opiates or combination analgesics with barbiturates, caffeine Avoid opiates or combination analgesics with barbiturates, caffeine Restrict the use to no more than two days/doses per week Restrict the use to no more than two days/doses per week NSAID has the lowest potential for medication overuse NSAID has the lowest potential for medication overuse

11 New Rx on the Horizon CGRP antagonists or Gepants CGRP antagonists or Gepants Glutamate Receptor Antagonists Glutamate Receptor Antagonists Vanilloid (TRPV1) receptor antagonists Vanilloid (TRPV1) receptor antagonists Nitric Oxide Synthetase inhibitors Nitric Oxide Synthetase inhibitors Prostanoid Receptor Antagonist Prostanoid Receptor Antagonist

12 New ways of Established Rx Inhaled version of DHE (MAP LEVADEX © ) Inhaled version of DHE (MAP LEVADEX © ) Triptans Triptans Melts and sprays Melts and sprays Needle free injection (intraject) Needle free injection (intraject) Transdermal patches (Zelrix) Transdermal patches (Zelrix) Sumnap (sumatriptan Naproxen combination) Sumnap (sumatriptan Naproxen combination)

13 MIGRAINE PROPHYLAXIS 03/05/ When should I give migraine prophylaxis? When should I give migraine prophylaxis? Prophylaxis is used to reduce the number of attacks in circumstances when acute therapy, used appropriately, gives inadequate symptom control. (BASH GUIDELINES 2010)

14 03/05/ Consensus view on migraine prophylaxis Should be offered to patients with 6 or more headache days per month; 4 or more days with some impairment; or 3 or more days with severe functional impairment Should be offered to patients with 6 or more headache days per month; 4 or more days with some impairment; or 3 or more days with severe functional impairment Should be considered with 4–5 days per month with normal functioning; 3 days with some impairment and 2 days with severe impairment Should be considered with 4–5 days per month with normal functioning; 3 days with some impairment and 2 days with severe impairment Should not be given to patients with <4 days of headache per month with normal functioning; or no more than 1 day per month regardless of impairment Should not be given to patients with <4 days of headache per month with normal functioning; or no more than 1 day per month regardless of impairment 1. Lipton RB et al. Neurology 2007;68:343–349.

15 03/05/ Migraine prophylaxis treatment options Non-pharmacological 1,2 Non-pharmacological 1,2 Behavioural lifestyle changes Behavioural lifestyle changes Anxiety management, psychotherapy and physiotherapy Anxiety management, psychotherapy and physiotherapy Pharmacological Pharmacological Few agents specifically licensed for migraine prophylaxis Few agents specifically licensed for migraine prophylaxis 1. World Health Organization (WHO) in collaboration with the European Headache Federation (EHF). J Headache Pain 2007;8:S1– Lipchik GL. American Headache Society, Accessed April 2012.

16 03/05/ Non-drug interventions Acupuncture has little benefit, if any at all Acupuncture has little benefit, if any at all Physiotherapy for the neck as an adjunctive treatment may be useful Physiotherapy for the neck as an adjunctive treatment may be useful Indian head massage may be useful but the evidence is anecdotal Indian head massage may be useful but the evidence is anecdotal Relaxation therapy, stress reduction and coping strategies are helpful Relaxation therapy, stress reduction and coping strategies are helpful These interventions are in need of formal evaluation These interventions are in need of formal evaluation Yoga and meditation are said to enhance stress management and appeal to some people 1 Yoga and meditation are said to enhance stress management and appeal to some people 1 Homeopathy offers no value 2 Homeopathy offers no value 2 1. BASH Guidelines Accessed March Whitmarsh TE et al. Cephalalgia 1997;17:600–4.

17 03/05/ Pharmacological options for migraine prophylaxis 1,2 Amine modulation: Amine modulation: Beta blockers Beta blockers 5-HT blockers (pizotifen, methysergide) 5-HT blockers (pizotifen, methysergide) Channel modulation: Channel modulation: Anticonvulsants (topiramate, epilim*) Anticonvulsants (topiramate, epilim*) Tricyclic Antidepressants Tricyclic Antidepressants Amitriptyline* Amitriptyline* ACE inhibition: ACE inhibition: Lisinopril* Lisinopril* * Currently not licensed for migraine prophylaxis in the UK 1. BASH Accessed August Scottish Intercollegiate Guidelines Network

18 03/05/ Beta blockers First-line if not contraindicated by asthma, heart failure, peripheral vascular disease or depression First-line if not contraindicated by asthma, heart failure, peripheral vascular disease or depression Use of propranolol in migraine prophylaxis 1 : Use of propranolol in migraine prophylaxis 1 : 58 propranolol studies met the inclusion criteria, of which 26 were placebo controlled 58 propranolol studies met the inclusion criteria, of which 26 were placebo controlled Overall relative risk of response to treatment was 1.94 (95% CI 1.61 to 2.35) Overall relative risk of response to treatment was 1.94 (95% CI 1.61 to 2.35) 17 trials showed a significant superiority over placebo, 7 a trend for propranolol and 2 no difference 17 trials showed a significant superiority over placebo, 7 a trend for propranolol and 2 no difference Commonly reported adverse events include cold extremities, reduced exercise tolerance, nightmares and dizziness Commonly reported adverse events include cold extremities, reduced exercise tolerance, nightmares and dizziness 1. Linde K et al. Cochr Database of Syst Rev 2004, Issue 2. Art. No.: CD

19 03/05/ Amitriptyline Used widely second only to beta-blockers Used widely second only to beta-blockers 3 small trials of amitriptyline (all before 1987) show 21–42% reduction in number of attacks 3 small trials of amitriptyline (all before 1987) show 21–42% reduction in number of attacks May be used first-line when migraines co-exist with troublesome tension-type headache, another chronic pain condition, disturbed sleep or depression May be used first-line when migraines co-exist with troublesome tension-type headache, another chronic pain condition, disturbed sleep or depression Commonly reported adverse events include dry mouth, sedation, dizziness and nausea 1 Commonly reported adverse events include dry mouth, sedation, dizziness and nausea 1 Dose used ranges between 10 and 150 mg per day 1 Dose used ranges between 10 and 150 mg per day 1 Individual tolerance to dosages varies and titration is highly dependent on side-effects experienced Individual tolerance to dosages varies and titration is highly dependent on side-effects experienced 1. Amitriptyline Summary of Product Characteristics Rosemount Pharmaceuticals Limited.

20 03/05/ Topiramate Clinical trials suggest efficacy equal to sodium valproate 1 Clinical trials suggest efficacy equal to sodium valproate 1 Use of topiramate in migraine prophyalxis 2 : Use of topiramate in migraine prophyalxis 2 : 6 (of 6) topiramate studies showed overall superiority to placebo in the combined analysis (OR 3.34; 95% CI 2.36 to 4.73) with noticeable variation in the odds ratio across the studies 2 6 (of 6) topiramate studies showed overall superiority to placebo in the combined analysis (OR 3.34; 95% CI 2.36 to 4.73) with noticeable variation in the odds ratio across the studies 2 A dose of 100 mg reports a 50% response rate 3 A dose of 100 mg reports a 50% response rate 3 Cognitive side effects and tingling sensation in fingers and toes often limit its use Cognitive side effects and tingling sensation in fingers and toes often limit its use Around a quarter of patients report loss of weight of around 10% and can act as a mood stabiliser Around a quarter of patients report loss of weight of around 10% and can act as a mood stabiliser 1. Shaygannejad V et al. Headache 2006;46: 642–8. 2. Chronicle EP et al. Cochr Database of Syst Rev 2004, Issue 3. Art. No.: CD Mathew N et al. Neurology 2003;60(Suppl. 1): A336.

21 03/05/ Valproate Sodium valproate has a response rate of around 44% 1 Sodium valproate has a response rate of around 44% 1 It does not reduce the efficacy of hormonal contraception It does not reduce the efficacy of hormonal contraception Use of valproate in migraine prophyalxis 2 : Use of valproate in migraine prophyalxis 2 : 4 (of 4) valproate studies showed active treatment was superior to placebo in reduction in migraine frequency (OR 3.34; 95%CI 1.46 to 7.67) 2 4 (of 4) valproate studies showed active treatment was superior to placebo in reduction in migraine frequency (OR 3.34; 95%CI 1.46 to 7.67) 2 Adverse events reported include nausea, asthenia, somnolence, weight gain and alopecia Adverse events reported include nausea, asthenia, somnolence, weight gain and alopecia Blood cell count, platelet count, bleeding time and coagulation tests are recommended prior to starting treatment and in case of spontaneous bruising or bleeding Blood cell count, platelet count, bleeding time and coagulation tests are recommended prior to starting treatment and in case of spontaneous bruising or bleeding Liver dysfunction is reported rarely Liver dysfunction is reported rarely 1. Klapper J Cephalalgia 1997;17: 103–8. 2. Chronicle EP et al. Cochr Database of Syst Rev 2004, Issue 3. Art. No.: CD

22 03/05/2015 Few Clinical Trials Have Focused on Preventive Pharmacotherapy in Chronic Migraine 22 Treatment Evidence for Use in Chronic Migraine Anticonvulsants: Valproate Topiramate Gabapentin Valproate Topiramate Gabapentin Small double-blind, placebo-controlled in CM 1,2 Double-blind, placebo-controlled trials in CM 3,4 One double-blind, placebo-controlled trial in CDH 5 Antidepressants: Amitriptyline Fluoxetine Tizanidine Amitriptyline Fluoxetine Tizanidine Small open-label trial in TM 6 Small double-blind, placebo-controlled trial in CDH 7 Small double-blind, placebo-controlled trial in CDH 8 Beta-blockers No evidence that they are effective in CM Calcium channel blockers No evidence that they are effective in CM ACE inhibitors and ARBs No evidence that they are effective in CM 1. Yurekli VA et al. J Headache Pain 2008;9:37– Bartolini M et al. Clin Neuropharmacol 2005;28:277– Diener HC et al. Cephalalgia 2007;27:814– Silberstein SD et al. Headache 2007;47:170– Spira PJ et al. Neurology 2003;61:1753– Krymchantowski AV et al. Headache 2002;45:510– Saper JR et al. Headache 1994;34:497– Saper JR et al. Headache 2002;42:470–482. ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker.

23 EPISODIC VERSUS CHRONIC EPISODIC EPISODIC MIGRAINE MIGRAINE TENSION HEADACHE TENSION HEADACHE CLUSTER HEADACHE CLUSTER HEADACHE CHRONIC CHRONIC CHRONIC MIGRAINE (CM) CHRONIC MIGRAINE (CM) CHRONIC TENSION TYPE HEADACHE CHRONIC TENSION TYPE HEADACHE MEDICATION OVERUSE HEADACHE (MOH) MEDICATION OVERUSE HEADACHE (MOH) CHRONIC CLUSTER HEADACHE CHRONIC CLUSTER HEADACHE

24 Chronic Migraine The IHS 2006 Revised Classification previously Triptan/Ergot responsive? Headache on > 15 days month with features of Migraine type headache On > 8 days / month* for > 3 months without other cause of headache With or without Analgesic Medication Overuse Headache? * ICHD-2 = Previously >15

25 CHRONIC MIGRAINE Under-diagnosed and Under-treated Under-diagnosed and Under-treated Most disabling form of headache disorder 1 Most disabling form of headache disorder 1 Co-morbidities are more common 2 Co-morbidities are more common 2 Trigger factors more pronounced than episodic variety 3 Trigger factors more pronounced than episodic variety % overuse painkillers % overuse painkillers 4 Patients may have low pain threshold and abnormal cortical processing 5 Patients may have low pain threshold and abnormal cortical processing 5 1. Blumenfield, Buse Kelman Allena 2009

26 26 Chronic Migraine: Multifaceted Approach to Therapy Chronic migraine management Education, support, managing expectations, and close follow-up Lifestyle modifications, behavioral therapy Pharmacologic therapy Dodick DW N Engl J Med 2006;354:158–165.

27 CM and MOH: Controversy IHS criteria exclude MO in defining CM 1 IHS criteria exclude MO in defining CM 1 Preventive treatment first or deal with MOH 2,3,4 Preventive treatment first or deal with MOH 2,3,4 Does MO reduce efficacy of preventive agent? 5 Does MO reduce efficacy of preventive agent? 5 Topiramate trial showed equal response in both arms i.e. with or without MOH 6 Topiramate trial showed equal response in both arms i.e. with or without MOH 6 1.ICHD II Hagen J Headache Pain Lovell Curr Opin Neurol Rossi Euro J of Neurol Hagen Cephalalgia Deiner Cephalalgia 2007

28 GREATER OCCIPITAL NERVE BLOCK (GON) Local anaesthetic +/- Steroids Local anaesthetic +/- Steroids 50% respond for up to 1 month 1,2 50% respond for up to 1 month 1,2 20% no benefit 3 20% no benefit 3 Local discomfort and alopecia 4 Local discomfort and alopecia 4 1. Afridi Pain Ashkenazi JNNP Shields Neurology Tobin & Fitman Headache 2009

29

30 2 Trials: PREEMPT1 and PREEMPT 2 Phase 3, parallel-group, placebo-controlled studies of Botulinum toxin A U in Chronic Migraine 1384 patients randomised (Botulinum toxin A 688, Placebo 696) 31 injections per treatment session Botulinum Toxin A in Chronic Migraine PREEMPT Studies Diener HC et al., Cephalalgia Jul;30(7): Aurora SK et al., Cephalalgia Jul;30(7): Dodick DW et al., Headache Jun;50(6):921-36

31 p<0.001 Nearly 70% of patients treated with BOTOX ® throughout the entire study experienced ≥50% reduction in migraine days from baseline at Week 56 (67.8% vs. 59.6% for placebo; p=0.018) 3 Nearly 70% of patients treated with BOTOX ® throughout the entire study experienced ≥50% reduction in migraine days from baseline at Week 56 (67.8% vs. 59.6% for placebo; p=0.018) 3 Mean ± standard error. The double-blind phase included 688 subjects in the BOTOX ® group and 696 in the placebo group. Migraine days at baseline: 19.1 BOTOX ® group vs 18.9 placebo group, p= Dodick DW et al. Headache 2010;50:921– Aurora SK et al. Presented at IHC Allergan Data on File – 50% responder rate at Week 56. Mean change in frequency migraine days from baseline (days/28-day period) Study week BOTOX ® (n=688) Placebo (n=696) p=0.018 p=0.01 p=0.024 p=0.013 p=0.003 p=0.006 p=0.003 p<0.001 Double-blind phase: BOTOX ® vs. placebo Open-label phase: All patients on BOTOX ® Mean change in frequency of migraine days from baseline (days/28-day period) p<0.001 PREEMPT POOLED ANALYSIS: MEAN CHANGE FROM BASELINE IN FREQUENCY OF MIGRAINE DAYS

32 TRANSCRANIAL MAGNETIC STIMULATION TMS devices deliver a brief magnetic pulse to the scalp and underlying cortex, altering firing patterns TMS devices deliver a brief magnetic pulse to the scalp and underlying cortex, altering firing patterns targets cortical spreading depression (CSD) targets cortical spreading depression (CSD) CSD is a wave of CSD is a wave of excitation followed by a wave of inhibition

33 03/05/ Transcranial Magnetic Stimulation for Migraine: A safety Review: Dodick et al Headache 2010;50(7):

34 ( Lipton et al., Lancet Neurol 2010;9: ) % Patients Transcranial magnetic stimulation for migraine Randomised double-blind placebo controlled study Include: 30% aura episodes, aura leads to headache 90% Exclude: Prolonged aura, MOH TMS- 0.9T for 180 ms; Sham- click and vibrate Primary endpoint: 2 hr pain free plus non-inferiority for nausea/photo/phono Blinding: Thought they got active, 67% Sham and 72% active n = *

35 Occipital Nerve Stimulator: St Jude’s device CE Marked CE Marked Chronic Migraine and intractable TAC Chronic Migraine and intractable TAC 03/05/201535

36 (Saper et al., AHS 2008) % Occipital nerve stimulation in chronic migraine ONSTIM Double-blind randomized parallel group sham stimulation controlled study ** * n = NS *P = 0.032; **P = Single Blind, Prospective Feasibility Study N = 66 Failed two preventive Rx

37 (Lipton et al., Cephalalgia 2009;29:30- IHC2009) days Occipital nerve stimulation in migraine & chronic migraine- PRISM n = NS Double blind randomised parallel group sham stimulation controlled study on patients failed two preventative treatments Prospective DB controlled N = 132 Trial Stimulation Negative Study

38 Gamma Core Vagal Nerve Stimulator Received CE Marked Received CE Marked Low ampere Stimulation Low ampere Stimulation Prophylaxis as well as acute Treatment. Prophylaxis as well as acute Treatment. 03/05/201538

39 MOH: Definition IHS 2004, Revised 2005*, Appendix Criteria 2006 Headache present on > 15 d/month for > 3 months Headache present on > 15 d/month for > 3 months Regular overuse for > 3 months of Regular overuse for > 3 months of Triptan or ergot or opiates or combination analgesics > 10 d/month Triptan or ergot or opiates or combination analgesics > 10 d/month Simple analgesics or combination with above > 15 d/month Simple analgesics or combination with above > 15 d/month Headache developed or worsened during overuse Headache developed or worsened during overuse *Probable until headache improves after withdrawal

40 Which Medication? Combination analgesic 39-42% Combination analgesic 39-42% Simple Analgesic 29-38% Simple Analgesic 29-38% Triptans 12-20% Triptans 12-20% Opiates 6% Opiates 6% Ergotamine 4-11% Ergotamine 4-11% MOH develops faster with triptan than simple analgesics and similarly withdrawal symptoms are much milder with triptans MOH develops faster with triptan than simple analgesics and similarly withdrawal symptoms are much milder with triptans Relja et al Headache 2004 Zeeberg et al Cephalalgia 2006 Katsarava et al 2000,2001

41 MOH: Rx Strategy How?Abrupt or Gradual How?Abrupt or Gradual Abrupt with simple analgesic/triptan Abrupt with simple analgesic/triptan Gradual with combination analgesic, opiates 4 Gradual with combination analgesic, opiates 4 Worse before better; short duration for rebound with triptan than combination and opiates 1 Worse before better; short duration for rebound with triptan than combination and opiates 1 When?Before or after preventive When?Before or after preventive Where? IP or OP Where? IP or OP OP as first line and brief IP if no motivation or failed OP 2,3 OP as first line and brief IP if no motivation or failed OP 2,3 1. Diener and Katsarava Hering and Steiner Rossi et al Everz & Marziniak 2010

42 What to expect after withdrawal? 70% get worse 70% get worse Withdrawal symptoms of nausea, vomiting, sleep disturbance and autonomic symptoms Withdrawal symptoms of nausea, vomiting, sleep disturbance and autonomic symptoms Katsarava et al 2002 Headache intensity worsens at day 2-4 before improvement

43 Rx for withdrawal symptoms Steroids: controversial 1,2,3 Steroids: controversial 1,2,3 Naproxen 500 mg bd days 4 Naproxen 500 mg bd days 4 IV DHE intermittent/continuous +/- metoclopramide 5,6,7 IV DHE intermittent/continuous +/- metoclopramide 5,6,7 IV Valproate 8 IV Valproate 8 IV clonidine 9, Prochlorperazine 10, Tizanidine 11 IV clonidine 9, Prochlorperazine 10, Tizanidine Krymchantowski and Barbosa Pagelar et al Boe et al Mitsikostas and Jumah Boes et al Silberstein et al Ford and Ford Schwartz et al Silberstein et al Le et al Smith Krymchantowski and Barbosa Pagelar et al Boe et al Mitsikostas and Jumah Boes et al Silberstein et al Ford and Ford Schwartz et al Silberstein et al Le et al Smith 2002

44 PROGNOSIS OF MOH 2 WEEKS 2 WEEKS 23% COMBINATION ANALGESICS 23% COMBINATION ANALGESICS 85% TRIPTANS 85% TRIPTANS ONE YEAR ONE YEAR 35-60% 35-60% 5 YEARS 5 YEARS 50% RELAPSE 50% RELAPSE 85% 57% 23%

45 EPISODIC VERSUS CHRONIC EPISODIC EPISODIC MIGRAINE MIGRAINE TENSION HEADACHE TENSION HEADACHE CLUSTER HEADACHE CLUSTER HEADACHE CHRONIC CHRONIC CHRONIC MIGRAINE (CM) CHRONIC MIGRAINE (CM) CHRONIC TENSION TYPE HEADACHE CHRONIC TENSION TYPE HEADACHE MEDICATION OVERUSE HEADACHE (MOH) MEDICATION OVERUSE HEADACHE (MOH) CHRONIC CLUSTER HEADACHE CHRONIC CLUSTER HEADACHE

46 EPISODIC CLUSTER HEADACHE 100% oxygen 4-8 litres/min or immigran sc injection 6 mg or nasal spray for acute attack 100% oxygen 4-8 litres/min or immigran sc injection 6 mg or nasal spray for acute attack Steroids to induce remission Steroids to induce remission Verapamil Verapamil Methysergide Methysergide Pizotifen Pizotifen Topiramate Topiramate Gabapentin Gabapentin

47 CHRONIC CLUSTER HEADACHE Lithium Lithium Other drugs used in episodic Other drugs used in episodic Can be refractory Can be refractory GON injection GON injection ONS ONS Deep Brain Stimulation Deep Brain Stimulation

48 INDOMETACIN RESPONSIVE HEADACHE Absolute Response Absolute Response Paroxysmal Hemicrania Paroxysmal Hemicrania Hemicrania Continua Hemicrania Continua Partial Response Partial Response Primary Stabbing headache Primary Stabbing headache Hypnic Headache Hypnic Headache Primary cough, exertional or coital headache Primary cough, exertional or coital headache

49 THANKS JOIN BASH JOIN BASH ELECTRONIC OR PAPER COPY OF CEPHALALGIA ELECTRONIC OR PAPER COPY OF CEPHALALGIA REGULAR NEWSLETTERS REGULAR NEWSLETTERS INVITATION TO BASH EVENTS INVITATION TO BASH EVENTS ABILITY TO CONTRIBUTE TO RESEARCH THROUGH INTERACTIVE WEBSITE (ABOUT TO LAUNCH) ABILITY TO CONTRIBUTE TO RESEARCH THROUGH INTERACTIVE WEBSITE (ABOUT TO LAUNCH)


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