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Post Traumatic Headache Alan G Finkel MD FAAN FAHS Contractor supporting the Defense and Veteran Brain Injury Center (DVBIC) Womack Army Medical Center, Ft Bragg, NC 20SEP2013 Disclosures • With regards to this talk the speaker has no financial conflicts to Disclose • During the course of this talk I will mention off label use of medications • THE ARE NO APPROVED DRUGS FOR CHRONIC POST TRAUMATIC HEADACHE • Other Affiliations – – – – President and CEO, The Carolina Headache Foundation, Chapel Hill , NC Chair, PTH Section, American Headache Society Director, Carolina Headache Institute , Chapel Hill, NC Professor, University of North Carolina • The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of Defense or Veterans Affairs position, policy or decision unless so designated by other documentation. • This research was funded by the Department of Defense, U.S. Army, Defense and Veterans Brain Injury Center, in part through a contract with The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. • In the conduct of research where humans are the subjects, the investigator(s) adhered to the policies regarding the protection of human subjects as prescribed by Code of Federal Regulations (CFR) Title 45, Volume 1, Part 46; Title 32, Chapter 1, Part 219; and Title 21, Chapter 1, Part 50 (Protection of Human Subjects). 2 http://www.afhsc.mil/viewMSMR?file=2012/v19_n05. pdf#Page=17 3 Finkel AG, Headache 2010; 50: 1259 - 1261. 4 Growing Interest Source: PubMed accessed 08122013 5 Traumatic Brain Injury (TBI) 6 The Surge? # of Publications 70 60 50 40 30 # o f Publications 20 10 0 Source: PubMed accessed 08122013 7 5. Headache attributed to head and/or neck trauma 5.1 Acute post-traumatic headache 5.2 Chronic post-traumatic headache 5.3 Acute headache attributed to whiplash injury 5.4 Chronic headache attributed to whiplash injury 5.5 Headache attributed to traumatic intracranial haematoma 5.6 Headache attributed to other head and/or neck trauma 5.7 Post-craniotomy headache ©International Headache Society 2003/5 8 5.2.2 Chronic post-traumatic headache attributed to mild head injury A. Headache, no typical characteristics known, fulfilling criteria C and D B. Head trauma with all the following: 1. either no loss of consciousness, or loss of consciousness of <30 minutes’ duration 2. Glasgow Coma Scale (GCS) >13 3. symptoms and/or signs diagnostic of concussion C. Headache develops within 7 days after head trauma D. Headache persists for >3 months after head trauma ©International Headache Society 2003/5 9 Primary or secondary headache? Primary: • no other causative disorder ©International Headache Society 2003/5 10 Primary or secondary headache? Secondary (i.e., caused by another disorder): • new headache occurring in close temporal relation to another disorder that is a known cause of headache • Worsening of a pre-existing headache disorder ©International Headache Society 2003/5 11 IS POST-TRAUMATIC HEADACHE (PTH) DIFFERENT? • Case control (n = 46) • MVC: 52%; mild: 88% PTH CTT M w/o A Other PCS 75% 21% 4% 48% “natural” population “40%” 57% <12% (cluster <1% • No cases of migraine with aura or cluster • “Criteria” met by both groups Haas, DC, Chronic post-traumatic headaches classified and compared with natural headaches, Cephalalgia 1996; 16: 486 - 93 12 Natural History of PTH • Walker study (n=109) with moderate or severe TBI at VA rehabilitation facilities; mostly car accidents Source: Walker 2005, Headache after moderate and severe TBI: A longitudinal analysis 13 Natural History of PTH Acute: 38% 6 months: 36% (16% delayed) Source: Figure 1 from Walker 2005 12 months: 35% (16% delayed) 14 Natural History after Mod-Sev TBI Hoffman JM, Lucas S, Dikmen S, Braden CA, Brown AW, Brunner R, Diaz-Arrastia R, Walker WC, Watanabe TK, Bell KR. Natural history of headache after traumatic brain injury. J Neurotrauma. 2011 Sep;28(9):1719-25. 15 What is the Diagnosis of Headache after Head Injury? 16 What about mild TBI? Lucas S, Hoffman JM, Bell KR, Dikmen S. A prospective study of prevalence and characterization of headache following mild traumatic brain injury. Cephalalgia. 2013 Aug 6 17 Risk Factor - AGE Lucas S, et al. Cephalalgia. 2013 Aug 6 18 Risk Factor - GENDER Lucas S, et al. Cephalalgia. 2013 Aug 6 19 Headache Diagnosis after Mild TBI Lucas S, et al. Cephalalgia. 2013 Aug 6 20 Migraine With and Without Aura • At least 2 attacks • Lasts 4 – 72 hours • Characteristics (2/4) – – – – Unilateral Throbbing Moderate-severe intensity Pain worsened by exertion (>95%) • Associated symptoms (1/2) – Nausea or vomiting – Photophobia & phonophobia ICHD Cephalalgia, Vol 24, Supp 1, 2004 21 Migraine Is: • A “personal biology” with extremely high prevalence – Associated with • • • • Lower thresholds to light and sound . Trigeminovascular activation Dura Mater C fiber Nociceptors – Inflammation • • • • CGRP NKA Substance P Prostaglandins • Termination by triptans – 5HT 1B/D receptor agonists – NSAIDs 22 Migraine Is: • A neurovascular disorder – Cortical Spreading Depression leads to: – Trigeminovascular activation • Dura Mater • C fiber Nociceptors – Inflammation • • • • CGRP NKA Substance P Prostaglandins • Termination by triptans – 5HT 1B/D receptor agonists – NSAIDs 23 Headache in Civilian Population • Migraine – Males: 6% – Females: 18% – Proportion with aura: ~30% • Chronic daily headache – 3-4% of adult population – 50% have chronic migraine • ~0.5-1.0% with continuous headache 24 Migraine Prevalence by Age and Sex Rescaled Women: Prevalence 18% Men: Prevalence 6-7% Source: Data analysis from study referenced in Stewart WF, Lipton RB, Liberman J. Variation in migraine prevalence by race. Neurology 1996 Jul;47(1):52-59 25 Prolonged TNC Stimulation May Lead to Central Sensitization • Over-stimulation of the TNC • Repeated stimulations and activations may lead to chronicification • Chronic Migraine – More than 15 days of headache (US = 8 or more migraine days) – Affects 4% of the population – Is the main type of headache seen in headache clinics 26 GOALS OF PREVENTIVE TREATMENT • Decrease attack frequency (by 50%), intensity and duration • Improve responsiveness to acute Rx • Improve function and decrease disability 27 WHEN TO USE PREVENTIVE MANAGEMENT • Migraine significantly interferes with patient’s daily routine, despite acute Rx • Acute medications contraindicated, ineffective, intolerable AEs or overused • Frequent headache ( 2 attacks per week) • Uncommon migraine conditions • Patient preference 28 PREVENTIVE MEDICATIONS: DRUG CLASSES First Line • Anticonvulsants – Topiramate – Valproate • Beta Blockers – Metoprolol – Propranolol • Antidepressants – Amitriptyline • NSAIDs – Naproxen – Ibuprofen Complimentary • Herbal – Petacites • Minerals – Magnesium • Vitamin – Riboflavin/B2 • Other – CoQ10 29 Special Populations Youth and Adult Sports 30 Do athletes get headaches? 31 Sports and Headache • General population = 1% (Rasmussen) • Aerobic - cardio • Type and extent of exercise – Compression • “swimmers’ goggle” • “tight hat band” – “weightlifters’ headache” – trauma-triggered and post-traumatic 32 Post-traumatic Headache • 3.b. Headache arising from mechanisms that occur during exertion - Trauma – Not case controlled – Resemble primary headache disorders • “TTH is the most common” – “footballers’ migraine” – Cluster-like (case report) – Worsening of a pre-existing primary headache Kernick DP, Goadsby PJ; Royal College of General Practitioners; British Association for the Study of Headache. Guidance for the management of headache in sport on behalf of The Royal College of General Practitioners and The British Association for the Study of Headache. Cephalalgia. 2011 Jan;31(1):106-11 33 Differential and Evaluation • Rule out secondary cause – MRI • Arnold-Chiari malformations – Exertional – weight lifters • SAH • Arterial dissection • Cardiac ischemia – BP and ECG – Blood screening including TSH and diabetes • Consider: urinary catecholamines Kernick DP, Goadsby PJ; Royal College of General Practitioners; British Association for the Study of Headache. Guidance for the management of headache in sport on behalf of The Royal College of General Practitioners and The British Association for the Study of Headache. Cephalalgia. 2011 Jan;31(1):106-11 34 Treatment - Acute McCrory P, Heywood J, Ugoni A. Open label study of intranasal sumatriptan (Imigran) for footballer's headache. Br J Sports Med. 2005 Aug;39(8):552-4 35 Treatment - preventive • “no evidence base” • Amitriptyline: Tyler GS, McNeely HE, Dick ML. Treatment of post-traumatic headache with amitriptyline. Headache. 1980 Jul;20(4):213-6 – – – – – N = 23 Age (mean) = 35.2 Time from injury = 29 weeks (3 – 77) Injury type: Recreational (1); non-vehicular (2); vehicular (20) 13 /23 – excellent response 36 Youth sports • Is Universal – 38 million • Not including playground – Risk factors • Competition – Male: Football – Female: Soccer • Female • Prior concussion – High school injuries • > 90% report headache immediately after concussion – most symptoms resolve within a week (83%). • 1.5% symptoms > 1 month • Professional level – no specific reports • ? symptomatic 37 Headache prevalence after mild and moderate-severe TBI Blume HK, Vavilala MS, Jaffe KM, Koepsell TD, Wang J, Temkin N, Durbin D, Dorsch A, Rivara FP. Headache after pediatric traumatic brain injury: a cohort study. Pediatrics. 2012 Jan;129(1):e31-9 38 Does Age or Gender Determine Headache After TBI? Blume HK, Vavilala MS, Jaffe KM, Koepsell TD, Wang J, Temkin N, Durbin D, Dorsch A, Rivara FP. Headache after pediatric traumatic brain injury: a cohort study. Pediatrics. 2012 Jan;129(1):e31-9 39 Treatment of Youth Sports PTH • Cognitive rest is controversial • When is prescription medication indicated? • Consensus recommendations – Preventive • Amitriptyline • Topamax (duh?) • Beta blockers – Acute • • • • Triptans are not as effective in adolescents and post-adolescents NSAIDs ?Baclofen Avoid opioids • Behavioral changes should be addressed – Biofeedback 40 http://www.cdc.gov/concussion/pdf/poster_Eng.pdf 41 http://www.cdc.gov/concussion/pdf/poster_Eng.pdf 42 Where are we now? • Headache is a recognized sequelae of youth sports concussion – RTP guidelines are not specific if headache is the only remaining symptom • Is persistent headache: – a cardinal sign? – a predictive variable? – a reason to remain out of play? – a (new onset) PRIMARY headache? 43 Special Populations Military 44 Medical Encounters for Migraine Active Duty Population Source: Medical Surveillance Monthly Report (MSMR) Vol 19 No. 2 Feb 2012 45 46 Hoge et al, Mild Traumatic Brain Injury in U.S. Soldiers Returning from Iraq. N Engl J Med 2008;358:453-63. 47 Hoge et al, Mild Traumatic Brain Injury in U.S. Soldiers Returning from Iraq. N Engl J Med 2008;358:453-63. 48 Post-Deployment Headache • Headache / migraine is common during or following deployment • Complicates the interpretation of posttraumatic headache data in military populations 49 Headache in recently deployed soldiers (all) Source: Theeler et al, Prevalence and Impact of Migraine Among U.S. Army Soldiers deployed in support of Operation Iraqi Freedom, Headache 2008; n=2726 50 Headache Type Source: Scher et al, Headache Disorders in Recently Deployed Soldiers With and Without Traumatic Brain Injury, AAN Annual Meeting April 2010 51 Frequency Source: Scher et al (Finkel), Headache Disorders in Recently Deployed Soldiers With and Without Traumatic Brain Injury, AAN Annual Meeting April 2010 52 What Kind of Headaches Do Soldiers Have After Mild TBI? 53 Headache Characteristics per SM All Blast Non-blast # of Headaches (mean, range) 2.2 (1 – 3) 2.4 (2 – 3) 2 (1 – 3) Continuous headache (n, %) 13 (92.9) 9 (81.8) 22 (88) Finkel et al, Headache 2010 54 Headache Onset Continuous (22/25) vs Episodic %) Finkel et al, Headache 2010 55 Density Finkel et al, Headache 2010 56 Density: Continuous vs Episodic Finkel et al, Headache 2010 57 Primary Headache Diagnosis (per SM) Headache Diagnosis (ICHD). MIGRAINE (some had more than one migraine type) Migraine with aura (1.2) N 15 5 Chronic tension-type headache (2.3) 12 Chronic cluster headache (3.1.2) 3 Chronic paroxysmal hemicrania (3.3.2) 1 Chronic SUNA (A3.3.2) 1 Primary stabbing headache (4.1) 4 Hemicrania (4.7) 2010 Finkel etcontinua al, Headache 2 58 Secondary Headache Diagnosis Headache attributed to low cerebrospinal fluid pressure (7.2) 1 Headache attributed to disorder of the neck (11.2) 1 Headache attributed to craniocervical dystonia (11.2.3) 1 Headache or facial pain attribute to temporomandibular joint 1 (TMJ) disorder (11.7) Headache attributed to other disorder of cranium, neck eye, ears, 1 nose, etc. (11.8) Symptomatic trigeminal neuralgia (13.1.2) 2 Finkel et al, Headache 2010 Supraorbital neuralgia (13.6) 1 59 Observations: Headaches • Injuries were more than 2 years ago • Patients can describe multiple headaches • Headache onset can occur after one week – Continuous Headaches all start in less than one week • Headaches may be superficial (“outside”) and focal • Continuous Headaches are – Less severe – More aching and more neck pain – Can have migraine features • Episodic Headaches – May start after one week – Can be diagnosed using primary classification Finkel AG, Yerry J, Scher A, Choi YS. Headaches in soldiers with mild traumatic brain injury: findings and phenomenologic descriptions. Headache. 2012 Jun;52(6):957-65 60 TREATING PTH Based upon Diagnosis (sic) 61 Differential and Evaluation • Primary Headache • Secondary Headache – MRI • Intracranial Hypotension • Chiari Malformation (?) – Diffuser Tensor Imaging (DTI) - ? – Sleep Study – Neuro-optometry – Cervicogenic 62 Amitriptyline? Patil VK, St Andre JR, Crisan E, Smith BM, Evans CT, Steiner ML, Pape TL. Prevalence and treatment of headaches in veterans with mild traumatic brain injury. Headache. 2011 Jul-Aug;51(7):1112-21 63 A Valiant Attempt Erickson JC. Treatment outcomes of chronic post-traumatic headaches after mild head trauma in US soldiers: an observational study. Headache. 2011 Jun;51(6):932-44 64 A Losing Battle? Cohen SP, et al. Headaches during war: Analysis of presentation, treatment, and factors associated with outcome. Cephalalgia. 2011 Oct 18 65 A Novel Drug: Prazosin 66 Pathophysiology and Treatment A Modest Proposal 67 Outside or Inside: Does this explain why mTBI results in persistent headache? 68 Intracranial origin of extracranial pain “In this scenario, action potentials generated intracranially at the leptomeningeal pain fibers spread antidromically to collaterals that terminate outside the cranium, resulting in activation of neighboring somatic nociceptors through local release of proinflammatory neuropeptides in both the dura and the scalp. This concept would be consistent with extracranial perivascular edema observed in some patients undergoing amigraine attack (Graham and Wolff, 1938; Wolff et al., 1953). This scenario may explain the perception of “imploding headache” (i.e., perception of pain on the outside of the skull; Jakubowski et al., 2006) in migraine triggered by intracranial events, such as aura. Finally, the presence of CGRP fibers in calvarial sutures, endosteum, and periosteum in the present study may constitute a neural substrate for the perception of deformed, crushed, or broken skull during migraine.” (my emphasis) Kosaras B, Jakubowski M, Kainz V, Burstein R. Sensory innervation of the calvarial bones of the mouse. J Comp Neurol. 2009 Jul 20;515(3):331-48 69 Extracranial origin of intracranial pain “In this scenario, action potentials generated at extracranial collaterals of meningeal pain fibers spread antidromically to collaterals that terminate inside the cranium, resulting in local release of proinflammatory neuropeptides and activation of neighboring meningeal nociceptors. This scenario may explain the induction of migraine headache by extracranial triggers, such as tenderness of scalp muscles, or minor head trauma affecting the periosteum.” (emphasis mine) Kosaras B, Jakubowski M, Kainz V, Burstein R. Sensory innervation of the calvarial bones of the mouse. J Comp Neurol. 2009 Jul 20;515(3):331-48 70 Central or Peripheral? Jakubowski M, et al. Exploding vs. imploding headache in migraine prophylaxis with Botulinum Toxin A. Pain. 2006 Dec 5;125(3):286-95 71 Central or Peripheral? • Patients randomized on basis of: – Exploding: INSIDE OUT • Feels like the head is too small for the brain • A feeling of something trying to escape from inside the head – Imploding: OUTSIDE IN • Like a vice • Imploding description predicted a better outcome to Onabotulinum Toxin A treatment for Chronic Migraine Jakubowski M, et al. Exploding vs. imploding headache in migraine prophylaxis with Botulinum Toxin A. Pain. 2006 Dec 5;125(3):286-95 72 Onabotulinum Toxin A (OBA) for the Treatment of Chronic Post-Traumatic Headache in Service Members with a History of Mild Traumatic Brain Injury Yerry, Finkel, et al: Presented at the International Headache Congress, JUN2013 Boston, MA 73 Demographics (n = 64) Age Gender (M:F) Prior history of migraine (%) 31.3 + 7.5 (20 – 50) ns 63 : 1 ns 7 (10.9) p = 0.045* 74 Conclusions for the Study Outcomes were not influenced by PTSD Headache Days per month Patients with non-continuous headache but daily headache did better if a second continuous headache was no present Outcomes WERE influenced by History of headache prior to injury (negative) Number of treatments Time between injury and first treatment with OBA Continuous Headache 75 TREATMENT • The Bad News – No completed treatment trials – PTSD and other PCS • Co-morbidity or concurrency • The Good News – Treating the primary phenomenology works (sometimes) • Migraine type – Formulary based including Chronic Migraine (?)Tension type – Continuous headache? • Focal or nummular types • The outside and the inside • The exploding and imploding 76 Finally: What is it? TBI vs PTSD mTBI vs MUS* Headache *MEDICALLY UNEXPLAINED (ABLE) SYMPTOMS 77 Conclusions • Post Traumatic Headache is complex – Different populations – Primary and secondary headaches may coexist • Classification remains a challenge – Does the “boo-boo” matter? • Migraine and Chronic Migraine are the most common types – Will imaging show changes similar to non-traumatic migraine? • The 7 Day Rule may require revision – Do Headache Types “Mature”? • Treatment is slowly improving • Using drugs and treatments for Migraine and Chronic Migraine appear to have some promise 78 Thank you for your attention The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of Defense or Veterans Affairs position, policy or decision unless so designated by other documentation. 79