11 minute read
Persistent Post Traumatic Headache
Angelica P. Ahrens, MS, MBA Alan G. Finkel, MD, FAAN, FAHS
The most common sequala of concussion/mild Traumatic Brain Injury (mTBI) is new onset or worsened headache. Post Traumatic Headache is diagnosed as Persistent (pPTH) if present after three months.
Diagnosis
The Centers for Disease Control and Prevention (CDC) estimate 2.8 million Americans experience TBI annually. In a survey of 3009 Americans, one-quarter had sustained concussion and one-third had persistent symptoms, with 80% seeking treatment1 . The estimated prevalence of pPTH is 15 – 35% at 5 years2,3, with 35% having multiple weekly headaches and 60% reporting migraine/probable migraine2. At eleven-years, 54% of Veterans with deployment-TBI had disabling headaches at least two days a week and 44% were near daily4 .
The International Classification of Headache Disorders 3rd Edition5 classifies PTH by TBI severity: mild or moderate/severe. Acutely, headache characteristics are nonspecific. pPTH takes on features of migraine and other primary headaches. Worsening pre-existing headache is characteristic of secondary headache. The 7-day rule is a diagnostic criterion, requiring that headache occur within seven days of injury, regaining consciousness, or recovering the ability to report pain5; however, this rule has been challenged6 and may miss 20-50% of PTH.
The most common phenotype of pPTH is migraine. Primary headache diagnosis is based upon an accepted group of symptoms and characteristics. Using a 4-point scale (none-mild-moderatesevere), migraine is defined by discrete attacks lasting 4–72 hours with and without aura. Aura is less common and is recognized as the sine qua non of migraine. TABLE 1 shows diagnostic criteria for pPTH.
Evaluation
Taking the history is crucial in pPTH evaluation: time from injury, mechanisms, symptom severity, immediate effects including disorientation, post-traumatic amnesia (PTA), and loss of consciousness. The examiner must establish the phenomenology of headache: time course (intermittent or continuous), type and location of pain, and symptomatology, e.g., migraine associations of light and noise sensitivity. A brief neurologic examination should be performed with attention to the cranial nerves and long track signs. Routine imaging/blood testing is not necessary. If indicated, MRI is best. CT scan should be used in the acute period to rule out blood. Structural and functional changes7 include loss of cortical thickness8, cerebrovascular reactivity, and decreases in grey matter9. Tract changes in major cortical areas10, differences in connectivity11 , and disruption in hypothalamic function connectivity12 have been described. In acute PTH, a recent publication observed iron deposition in areas of recognition and pain processing13. Clinical symptoms correlate with imaging changes14 .
Veterans with deployment-related TBI have high-incidence migraine and chronic daily headache4. Migraine with aura (MWA) is the most common phenotype (41%4, 6% in our clinic-based study15). MWA is a potent predictor of pPTH16. The second most potent predictor is continuous or daily headache16. Seventy-five-percent of service members with TBI describe continuous headaches15. Perhaps most important is headache density/frequency. Using classification, we showed headache phenotypic diagnosis was not the determinant of outcomes15. Continuous duration, pain intensity, activities during headache, medication, history of headache and headache density predicted termination of military service.
Treatment
To treat pPTH, we use primary headache phenotype. There are no successful controlled trials for any medication, treatment, or technique.
Table 1. Diagnostic criteria for pPTH. Adapted from5 .
Table 1. Diagnostic criteria for pPTH. Adapted from5 . 5.2 Persistent headache attributed to traumatic injury to the head
Headache of more than three months’ duration caused by traumatic injury to the head. A. Any headache fulfilling criteria C and D B. Traumatic injury to the head1 has occurred C. Headache is reported to have developed within seven days after one of the following: 1. the injury to the head 2. regaining of consciousness following the injury to the head 3. discontinuation of medication(s) impairing ability to sense or report headache following the injury to the head D. Headache persists for >3 months after its onset E. Not better accounted for by another ICHD-3 diagnosis. 1Defined as a structural or functional injury resulting from the action of external forces upon the head.
A. Headache fulfilling criteria for 5.2 Persistent headache attributed to traumatic injury to the head
B. Head injury fulfilling both of the following: 1. associated with none of the following: – loss of consciousness for >30 minutes – Glasgow Coma Scale (GCS) score <13 – post-traumatic amnesia lasting >24 hours2 – altered level of awareness for >24 hours – imaging evidence of a traumatic head injury such as skull fracture, intracranial hemorrhage and/or brain contusion 2. associated with one or more of the following symptoms and/or signs: – transient confusion, disorientation or impaired consciousness – loss of memory for events immediately before or after the head injury – two or more of the following symptoms suggestive of mild traumatic brain injury: – nausea – vomiting – visual disturbances – dizziness and/or vertigo – gait and/or postural imbalance – impaired memory and/or concentration. 2Time between injury and resumption of normal continuous recall of events.
Triptans in soldiers showed 70-75% improvement17 . Occipital nerve blocks help but without long-lasting effects18 . Preventive medications include valproate, topiramate, amitriptyline, and gabapentin. Onabotulinum toxin has been utilized19, and showed improvements in soldiers20. A controlled study in Veterans also showed significant effectiveness21 .
Calcitonin Gene Related Peptide (CGRP) and its receptor are targets of migraine therapy. Erenumab and Fremanezumab are effective in reduction of headache days and migraine prevention, respectively, but the latter failed to reach its primary endpoint of improvement in moderate-to-severe headache days. Nonpharmacologic treatments can help PTH. Multidisciplinary treatments22 and lifestyle modification/cognitive behavioral therapy/ biofeedback showed dramatic changes in refractory pPTH23 . Improvements in headache intensity in pPTH were observed oneweek post-Transcranial Magnetic Stimulation but were not sustained at four-weeks24. Hyperbaric oxygen did not change pPTH25, nor did pulsed electromagnetic stimulation26 . Pre-injury headache28,29, psychiatric comorbidities28, PTA30, sleep/ fatigue30, headache severity27, neck stiffness31, symptoms in arms/ hands, dizziness/unsteadiness31, catastrophizing27, and pain modulation27 associate with outcome. This supports routine followup, which is rare, with only <10% of neurotrauma centers scheduling a routine follow-up after discharge from the emergency room and a modest 54% after hospital admission32. In the long-term, psychiatric comorbidities, employment status31 and lower recovery expectations/catastrophizing27 were most impactful.
Conclusion
Recovery appears dependent upon premorbid, peri- and post-injury characteristics and clinical markers. Females are more likely to demonstrate PTH and pPTH27 . pPTH is common after mTBI. Evaluation, diagnosis, and testing have shown promise. Evidence in support of a range of treatments is growing. Personalized paradigms of treatment are on the horizon.
References
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Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia Int J Headache. 2018;38(1):1-211. doi:10.1177/0333102417738202 6. Scher AI, Monteith TS. Epidemiology and classification of post-traumatic headache: what do we know and how do we move forward? Comment on Lucas et al., “Prevalence and characterization of headache following mild TBI.” Cephalalgia Int J Headache. 2014;34(2):83-85. doi:10.1177/0333102413499644 7. Schwedt TJ. Structural and Functional Brain Alterations in Post-traumatic Headache Attributed to Mild Traumatic Brain Injury: A Narrative Review. Front Neurol. 2019;10:615. doi:10.3389/fneur.2019.00615 8. Chong CD, Berisha V, Chiang CC, Ross K, Schwedt TJ. Less Cortical Thickness in Patients With Persistent Post-Traumatic Headache Compared With Healthy Controls: An MRI Study. Headache. 2018;58(1):53-61. doi:10.1111/head.13223 9. Burrowes SAB, Rhodes CS, Meeker TJ, Greenspan JD, Gullapalli RP, Seminowicz DA. Decreased grey matter volume in mTBI patients with post-traumatic headache compared to headache-free mTBI patients and healthy controls: a longitudinal MRI study. Brain Imaging Behav. 2020;14(5):1651-1659. doi:10.1007/s11682019-00095-7 10. Chong CD, Peplinski J, Berisha V, Ross K, Schwedt TJ. Differences in fibertract profiles between patients with migraine and those with persistent post-traumatic headache. Cephalalgia Int J Headache. 2019;39(9):1121-1133. doi:10.1177/0333102418815650 11. Maleki N, Finkel A, Cai G, et al. Post-traumatic Headache and Mild Traumatic Brain Injury: Brain Networks and Connectivity. Curr Pain Headache Rep. 2021;25(3):20. doi:10.1007/s11916-020-00935-y 12. Lu L, Li F, Wang P, Chen H, Chen YC, Yin X. Altered hypothalamic functional connectivity in post-traumatic headache after mild traumatic brain injury. J Headache Pain. 2020;21(1):93. doi:10.1186/s10194-020-011649 13. Nikolova S, Schwedt TJ, Li J, et al. T2* reduction in patients with acute post-traumatic headache. Cephalalgia Int J Headache. Published online October 13, 2021:3331024211048509. doi:10.1177/03331024211048509 14. Chong CD, Berisha V, Ross K, Kahn M, Dumkrieger G, Schwedt TJ. Distinguishing persistent posttraumatic headache from migraine: Classification based on clinical symptoms and brain structural MRI data. Cephalalgia Int J Headache. 2021;41(8):943-955. doi:10.1177/0333102421991819 15. Finkel AG, Yerry JA, Klaric JS, Ivins BJ, Scher A, Choi YS. Headache in military service members with a history of mild traumatic brain injury: A cohort study of diagnosis and classification. Cephalalgia Int J Headache. 2017;37(6):548-559. doi:10.1177/0333102416651285 16. Metti A, Schwab K, Finkel A, et al. Posttraumatic vs nontraumatic headaches: A phenotypic analysis in a military population. Neurology. 2020;94(11):e1137-e1146. doi:10.1212/WNL.0000000000008935 17. Scott BR, Uomoto JM, Barry ES. Impact of Pre-Existing Migraine and Other Co-Morbid or Co-Occurring Conditions on Presentation and Clinical Course Following Deployment-Related Concussion. Headache. 2020;60(3):526-541. doi:10.1111/head.13709 18. Larsen EL, Ashina H, Iljazi A, et al. Acute and preventive pharmacological treatment of post-traumatic headache: a systematic review. J Headache Pain. 2019;20(1):98. doi:10.1186/s10194-019-1051-7 19. Jia C, Lucchese S, Zhang F, Govindarajan R. The Role of Onabotulinum Toxin Type A in the Management of Chronic Non-migraine Headaches. Front Neurol. 2019;10:1009. doi:10.3389/fneur.2019.01009 20. Yerry JA, Kuehn D, Finkel AG. Onabotulinum toxin a for the treatment of headache in service members with a history of mild traumatic brain injury: a cohort study. Headache. 2015;55(3):395-406. doi:10.1111/ head.12495 21. Zirovich MD, Pangarkar SS, Manh C, et al. Botulinum Toxin Type A for the Treatment of Post-traumatic Headache: A Randomized, Placebo-Controlled, Cross-over Study. Mil Med. 2021;186(5-6):493-499. doi:10.1093/milmed/usaa391 22. Janak JC, Cooper DB, Bowles AO, et al. Completion of Multidisciplinary Treatment for Persistent Postconcussive Symptoms Is Associated With Reduced Symptom Burden. J Head Trauma Rehabil. 2017;32(1):1-15. doi:10.1097/HTR.0000000000000202 23. Baker VB, Eliasen KM, Hack NK. Lifestyle modifications as therapy for medication refractory posttraumatic headache (PTHA) in the military population of Okinawa. J Headache Pain. 2018;19(1):113. doi:10.1186/s10194-018-0943-2 24. Leung A, Metzger-Smith V, He Y, et al. Left Dorsolateral Prefrontal Cortex rTMS in Alleviating MTBI Related Headaches and Depressive Symptoms. Neuromodulation J Int Neuromodulation Soc. 2018;21(4):390-401. doi:10.1111/ner.12615 25. Skipper LD, Churchill S, Wilson SH, Deru K, Labutta RJ, Hart BB. Hyperbaric oxygen for persistent post-concussive symptoms: long-term follow-up. Undersea Hyperb Med J Undersea Hyperb Med Soc Inc. 2016;43(5):601-613. 26. Nelson DV, Esty ML. Neurotherapy for chronic headache following traumatic brain injury. Mil Med Res. 2015;2:22. doi:10.1186/s40779-015-0049-y 27. Naugle KM, Carey C, Evans E, Saxe J, Overman R, White FA. The role of deficient pain modulatory systems in the development of persistent post-traumatic headaches following mild traumatic brain injury: an exploratory longitudinal study. J Headache Pain. 2020;21(1):138. doi:10.1186/s10194-020-01207-1 28. Yue JK, Cnossen MC, Winkler EA, et al. Pre-injury Comorbidities Are Associated With Functional Impairment and Post-concussive Symptoms at 3- and 6-Months After Mild Traumatic Brain Injury: A TRACKTBI Study. Front Neurol. 2019;10:343. doi:10.3389/fneur.2019.00343 29. Sawyer K, Bell KR, Ehde DM, et al. Longitudinal Study of Headache Trajectories in the Year After Mild Traumatic Brain Injury: Relation to Posttraumatic Stress Disorder Symptoms. Arch Phys Med Rehabil. 2015;96(11):2000-2006. doi:10.1016/j.apmr.2015.07.006 30. 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Author Bios
Angelica P. Ahrens, MS, MBA, is a PhD candidate in Microbiology and Cell Science at the University of Florida. Her research is based in microbial underpinnings of mental health, chronic pain, and autoimmune disorders, with interest in prediction and education. She received her BS from Duke University in 2012 and trained in data analytics and microbiology at NSU Florida and UF, receiving an MBA and MS, respectively. She has presented at forums including National Academy for Neuropsychologists, International Neuropsychological Society, and Military Health System. She has co-authored original research in refereed journals including Cell Reports, Nutrients, American Journal of Sports Medicine, and Concussion.
Alan G. Finkel, MD, FAAN, FAHS, is a neurologist and headache specialist at the Carolina Headache Institute in Durham, NC. He received his MD from SUNY at Buffalo and completed neurology and subspecialty training in pain medicine and headache medicine at UNC at Chapel Hill. His work has included pain management, medical and headache medicine education and from 2008 – 2019 his work with the TBI team at Ft Bragg/Intrepid Spirit included research and peer reviewed publication on Post Traumatic Headache. An active editor, reviewer for major journals he also attends and chairs sections at NIH and the DOD/CDMRP.
