Search

Chronic post-traumatic headache (CPTH) after a mild traumatic brain injury (mTBI) has been reported in up to 60% of patients and can be extremely debilitating. While pharmacological treatments are typically used for CPTH, they frequently cause side effects and have limited effectiveness, leading individuals with CPTH to be unsatisfied with current treatment options and to seek nonpharmacological options. Acupuncture has been identified as a potential treatment option; however, the evidence in this population remains limited. The overall goal of this study was to examine the effect of a once weekly (e.g., low dose) versus twice weekly (e.g., high dose) of acupuncture treatment on CPTH in individuals with mTBI. Thirty-eight individuals were randomized to receive either 5 or 10 acupuncture treatments using a standard protocol over 5 weeks. The protocol consisted of 14 points using traditional acupuncture and 4 points using electroacupuncture. Headache outcomes, safety, treatment adherence, sleep quality, and quality of life (QOL) were assessed. The results showed that while there were no differences between dose groups for any of the outcomes assessed, acupuncture significantly reduced the number of headache days and headache pain intensity in individuals with CPTH. There were no significant changes in acute medication use or sleep quality. While there were some QOL improvements identified, these results should be interpreted with caution. Overall, acupuncture was shown to be safe and well-tolerated in people with CPTH after mTBI, and five acupuncture treatments using a standardized protocol shows promise in providing headache relief for this population.

Background: Post-traumatic headache (PTH) is a common comorbid symptom affecting at least one-third of patients with mild traumatic brain injury (mTBI). While neuroinflammation is known to contribute to the development of PTH, the cellular mechanisms in the trigeminal system crucial for understanding the pathogenesis of PTH remain unclear., Methods: A non-invasive repetitive mTBI (4 times with a 24-h interval) was induced in male mice and effect of mTBI was tested on either bregma or pre-bregma position on the head. Periorbital allodynia and spontaneous pain behavior were assessed using von Frey test and grimace score, respectively. Quantitative PCR was used to assess extent of mTBI pathology. RNA sequencing was performed to obtain transcriptomic profile of the trigeminal ganglion (TG), trigeminal nucleus caudalis (Sp5C) and periaqueductal gray (PAG) at 7 days post-TBI. Subsequently, quantitative PCR, in situ hybridization and immunohistochemistry were used to examine mRNA and protein expression of glia specific markers and pain associated molecules., Results: The repetitive impacts at the bregma, but not pre-bregma site led to periorbital hypersensitivity, which was correlated with enhanced inflammatory gene expression in multiple brain regions. RNA sequencing revealed mTBI induced distinct transcriptomic profiles in the peripheral TG and central Sp5C and PAG. Using gene set enrichment analysis, positive enrichment of non-neuronal cells in the TG and neuroinflammation in the Sp5C were identified to be essential in the pathogenesis of PTH. In situ assays also revealed that gliosis of satellite glial cells in the TG and astrocytes in the Sp5C were prominent days after injury. Furthermore, immunohistochemical study revealed a close interaction between activated microglia and reactive astrocytes correlating with increased calretinin interneurons in the Sp5C., Conclusions: Transcriptomics analysis indicated that non-neuronal cells in peripheral TG and successive in situ assays revealed that glia in the central Sp5C are crucial in modulating headache-like symptoms. Thus, selective targeting of glia cells can be a therapeutic strategy for PTH attributed to repetitive mTBI., Competing Interests: Declarations. Ethics approval and consent to participate: All animal procedures were conducted in accordance with the Office for Laboratory Animal Welfare (OLAW), National Institutes of Health (NIH) and American Veterinary Medical Association (AVMA) Guidelines for the Euthanasia of Animals guidelines and approved by the Uniformed Services University of the Health Sciences (USUHS) Institutional Animal Care and Use Committee (IACUC). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Posttraumatic headache (PTH) is a common and debilitating symptom following repetitive mild traumatic brain injury (rmTBI), and it mainly resembles a migraine-like phenotype. While modulation of the endocannabinoid system (ECS) is effective in treating TBI and various types of pain including migraine, the role of augmentation of endocannabinoids in treating PTH has not been investigated., Methods: Repetitive mild TBI was induced in male C57BL/6J mice using the non-invasive close-head impact model of engineered rotational acceleration (CHIMERA). Periorbital allodynia was assessed using von Frey filaments and determined by the "Up-Down" method. Immunofluorescence staining was employed to investigate glial cell activation and calcitonin gene-related peptide (CGRP) expression in the trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC) of the rmTBI mice. Levels of 2-arachidonoyl glycerol (2-AG), anandamide (AEA), and arachidonic acid (AA) in the TG, medulla (including TNC), and periaqueductal gray (PAG) were measured by mass spectrometry. The therapeutic effect of endocannabinoid modulation on PTH was also assessed., Results: The rmTBI mice exhibited significantly increased cephalic pain hypersensitivity compared to the sham controls. MJN110, a potent and selective inhibitor of the 2-AG hydrolytic enzyme monoacylglycerol lipase (MAGL), dose-dependently attenuated periorbital allodynia in the rmTBI animals. Administration of CGRP at 0.01 mg/kg reinstated periorbital allodynia in the rmTBI animals on days 33 and 45 post-injury but had no effect in the sham and MJN110 treatment groups. Activation of glial cells along with increased production of CGRP in the TG and TNC at 7 and 14 days post-rmTBI were attenuated by MJN110 treatment. The anti-inflammatory and anti-nociceptive effects of MJN110 were partially mediated by cannabinoid receptor activation, and the pain-suppressive effect of MJN110 was completely blocked by co-administration of DO34, an inhibitor of 2-AG synthase. The levels of 2-AG in TG, TNC and PAG were decreased in TBI animals, significantly elevated and further reduced by the selective inhibitors of 2-AG hydrolytic and synthetic enzymes, respectively., Conclusion: Enhancing endogenous levels of 2-AG appears to be an effective strategy for the treatment of PTH by attenuating pain initiation and transmission in the trigeminal pathway and facilitating descending pain inhibitory modulation., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: The insula is an important part of the posttraumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) neuropathological activity pattern. It is composed of functionally different subdivisions and each of which plays different role in PTH neuropathology., Methods: Ninety-four mTBI patients were included in this study. Based on perfusion imaging data obtained from arterial spin labelling (ASL) perfusion magnetic resonance imaging (MRI), this study evaluated the insular subregion perfusion-based functional connectivity (FC) and its correlation with clinical characteristic parameters in patients with PTH after mTBI and non-headache mTBI patients., Results: The insular subregions of mTBI + PTH (mTBI patients with PTH) and mTBI-PTH (mTBI patients without PTH) group had positive perfusion-based functional connections with other insular nuclei and adjacent discrete cortical regions. Compared with mTBI-PTH group, significantly increased resting-state perfusion-based FC between the anterior insula (AI) and middle cingulate cortex (MCC)/Rolandic operculum (ROL), between posterior insula (PI) and supplementary motor area (SMA), and decreased perfusion-based FC between PI and thalamus were found in mTBI + PTH group. Changes in the perfusion-based FC of the left posterior insula/dorsal anterior insula with the thalamus/MCC were significant correlated with headache characteristics., Conclusions: Our findings provide new ASL-based evidence for changes in the perfusion-based FC of the insular subregion in PTH patients attributed to mTBI and the association with headache features, revealing the possibility of potential neuroplasticity after PTH. These findings may contribute to early diagnosis of the disease and follow-up of disease progression., (© 2024. The Author(s).)

Background: Large conductance  calcium-activated potassium (BK Ca ) channels have been implicated in the neurobiological underpinnings of migraine. Considering the clinical similarities between migraine and persistent post-traumatic headache (PPTH), we aimed to examine whether MaxiPost (a BK Ca channel opener) could induce migraine-like headache in persons with PPTH., Methods: This is a randomized double-blind, placebo-controlled, two-way crossover study from September 2023 to December 2023. Eligible participants were adults with PPTH after mild traumatic brain injury who reported having no personal history of migraine. The randomized participants received a single dose of either MaxiPost (0.05 mg/min) or placebo (isotonic saline) that was infused intravenously over 20 minutes. The two experiment sessions were scheduled at least one week apart to avoid potential carryover effects. The primary endpoint was the induction of migraine-like headache after MaxiPost as compared to placebo within 12 hours of drug administration. The secondary endpoint was the area under the curve (AUC) values for headache intensity scores between MaxiPost and placebo over the same 12-hour observation period., Results: Twenty-one adult participants (comprising 14 females and 7 males) with PPTH were enrolled and completed both experiment sessions. The proportion of participants who developed migraine-like headache was 11 (52%) of 21 participants after MaxiPost infusion, in contrast to four (19%) participants following placebo (P = .02). Furthermore, the median headache intensity scores, represented by AUC values, were higher following MaxiPost than after placebo (P < .001)., Conclusions: Our results indicate that BK Ca channel opening can elicit migraine-like headache in persons with PPTH. Thus, pharmacologic blockade of BK Ca channels might present a novel avenue for drug discovery. Additional investigations are nonetheless needed to confirm these insights and explore the therapeutic prospects of BK Ca channel blockers in managing PPTH., Gov Identifier: NCT05378074., (© 2024. The Author(s).)

Background: The purpose of this study was to interrogate brain iron accumulation in participants with acute post-traumatic headache (PTH) due to mild traumatic brain injury (mTBI), and to determine if functional connectivity is affected in areas with iron accumulation. We aimed to examine the correlations between iron accumulation and headache frequency, post-concussion symptom severity, number of mTBIs, and time since most recent TBI., Methods: Sixty participants with acute PTH and 60 age-matched healthy controls (HC) underwent 3T magnetic resonance imaging including quantitative T 2 * maps and resting-state functional connectivity imaging. Between group T 2 * differences were determined using T-tests (p < 0.005, cluster size threshold of 90 voxels). For regions with T 2 * differences, two analyses were conducted. First, the correlations with clinical variables including headache frequency, number of lifetime mTBIs, time since most recent mTBI, and Sport Concussion Assessment Tool (SCAT) symptom severity scale scores were investigated using linear regression. Second, the functional connectivity of these regions with the rest of the brain was examined (significance of p < 0.05 with family wise error correction for multiple comparisons)., Results: The acute PTH group consisted of 60 participants (22 male, 38 female) with average age of 42 ± 14 years. The HC group consisted of 60 age-matched controls (17 male, 43 female, average age of 42 ± 13). PTH participants had lower T 2 * values compared to HC in the left posterior cingulate and the bilateral cuneus. Stronger functional connectivity was observed between bilateral cuneus and right cerebellar areas in PTH compared to HC. Within the PTH group, linear regression showed negative associations of T 2 * in the left posterior cingulate with SCAT symptom severity score (p = 0.05) and T 2 * in the left cuneus with headache frequency (p = 0.04)., Conclusions: Iron accumulation in posterior cingulate and cuneus was observed in those with acute PTH relative to HC; stronger functional connectivity was detected between the bilateral cuneus and the right cerebellum. The correlations of decreased T 2 * (suggesting higher iron content) with headache frequency and post mTBI symptom severity suggest that the iron accumulation that results from mTBI might reflect the severity of underlying mTBI pathophysiology and associate with post-mTBI symptom severity including PTH., (© 2024. The Author(s).)

Background: Phosphodiesterase 3 (PDE-3) inhibition have been implicated in the neurobiologic underpinnings of migraine. Considering the clinical similarities between migraine and persistent post-traumatic headache (PPTH), we aimed to ascertain whether PDE-3 inhibition can elicit migraine-like headache in persons with PPTH., Methods: We tested cilostazol, which inhibits PDE-3, in a randomized, double-blind, placebo-controlled, two-way crossover study involving persons with PPTH attributed to mild traumatic brain injury. The randomized participants were allocated to receive oral administration of either 200-mg cilostazol or placebo (calcium tablet) on two separate experiment days. The primary end point was the incidence of migraine-like headache during a 12-hour observation window post-ingestion. The secondary endpoint was the area under the curve (AUC) for reported headache intensity scores during the same observation window., Results: Twenty-one persons underwent randomization and completed both experiment days. The mean participants' age was 41.4 years, and most (n = 17) were females. During the 12-hour observation window, 14 (67%) of 21 participants developed migraine-like headache post-cilostazol, in contrast to three (14%) participants after placebo (P =.003). The headache intensity scores were higher post-cilostazol than after placebo (P <.001)., Conclusions: Our results provide novel evidence showing that PDE-3 inhibition can elicit migraine-like headache in persons with PPTH. Given that PDE-3 inhibition increases intracellular cAMP levels, our findings allude to the potential therapeutic value of targeting cAMP-dependent signaling pathways in the management of PPTH. Further investigations are imperative to substantiate these insights and delineate the importance of cAMP-dependent signaling pathways in the neurobiologic mechanisms underlying PPTH., Gov Identifier: NCT05595993., (© 2024. The Author(s).)

Objective: To ascertain the prevalence of and risk factors for post-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI)., Patients and Methods: A prospective, longitudinal, multicenter cohort study of patients with mTBI and orthopedic trauma controls who were enrolled from February 26, 2014, to August 8, 2018. The baseline assessment was conducted as soon as possible following evaluation at the emergency department. Follow-ups were scheduled at 2 weeks, 3 months, 6 months, and 12 months postinjury. Eligible patients with mTBI included those 18 years of age or older who presented to the emergency department within 24 hours of head injury warranting evaluation by noncontrast head computed tomography scan. Acute PTH was considered present when a patient reported a headache score of greater than or equal to 2 on the Rivermead Post-concussion Questionnaire at 2 weeks postinjury (ie, headache is at least a mild problem compared with pre-injury). Persistent PTH was defined when a patient with acute PTH reported a Rivermead Post-concussion Questionnaire headache score of greater than or equal to 2 at the scheduled follow-up examinations., Results: Acute PTH was reported by 963 (60.4%) of 1594 patients with mTBI at 2 weeks postinjury. Among those with acute PTH, 439 (52.4%) of 837 patients reported persistent PTH at 3 months postinjury. This figure decreased over time and 278 (37.5%) of 742 patients continued to report persistent PTH at 6 months, whereas 187 (28.9%) of 646 patients did so as well at 12 months postinjury. Risk factors for acute PTH included younger age, female sex, fewer years of formal education, computed tomography-positive scans, alteration of consciousness, psychiatric history, and history of migraine. Risk factors for persistent PTH included female sex, fewer years of formal education, and history of migraine., Conclusion: Post-traumatic headache is a prevalent sequela of mTBI that persists for at least 12 months in a considerable proportion of affected individuals. The attributable burden necessitates better patient follow-up, disease characterization, improved awareness of PTH in clinical practice, and identification of effective therapies., (Copyright © 2023 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: To ascertain whether intravenous infusion of calcitonin gene-related peptide (CGRP) can induce migraine-like headache in people with persistent post-traumatic headache attributed to mild traumatic brain injury (TBI) and no pre-existing migraine., Methods: A non-randomized, single-arm, open-label study at a single site in Denmark. Eligible participants were aged 18 to 65 years and had a known history of persistent post-traumatic headache attributed to mild TBI for ≥ 12 months. All participants received continuous intravenous infusion of CGRP (1.5 µg/min) over 20 min. A headache diary was used to collect outcome data until 12 h after the start of CGRP infusion. The primary end point was the incidence of migraine-like headache during 12-hour observational period., Results: A total of 60 participants completed the study protocol and provided data for the analysis of the primary end point. The median age was 32.5 (IQR, 25.5-43.0) years; 43 participants (72%) were female. Following CGRP infusion, 43 (72%) of 60 participants developed migraine-like headache during the 12-hour observational period. The median time to peak headache intensity was 40 min (IQR, 20-60), and the median peak headache intensity was 6 (IQR, 5-8) on the 11-point numeric rating scale., Conclusion: Intravenous infusion of CGRP is a potent inducer of migraine-like headache in people with persistent post-traumatic headache attributed to mild TBI. This observation underscores the importance of CGRP in the genesis of migraine-like headache that is often experienced by individuals who are afflicted by persistent post-traumatic headache. Further research is warranted to ascertain whether other signaling molecules also contribute to the disease mechanisms underlying post-traumatic headache., (© 2022. The Author(s).)

Objective: To investigate whether persistent post-traumatic headache attributed to mild traumatic brain injury (TBI) is associated with more pronounced pericranial tenderness and lower pressure pain thresholds (PPTs) in the head and neck region, compared with healthy controls., Methods: Patients with persistent post-traumatic headache (n = 100) and age- and gender-matched healthy controls (n = 100) were included between July 2018 and June 2019. Total tenderness score (TTS) was used to assess pericranial tenderness by bilateral manual palpation in eight muscles or tendon insertions. Summation was then used to calculate a TTS from 0 to 48 based on individual right- and left-sided scores; higher TTS score indicated more pronounced pericranial tenderness. PPTs were examined in m. temporalis and m. trapezius (upper and middle part) using an electronic pressure algometer that applies increasing blunt pressure at a constant rate., Results: The TTS score was higher in patients with persistent post-traumatic headache (median, 21; IQR, 12-31), compared with healthy controls (median, 10; IQR, 6-17; P < .001). PPTs were lower in patients with persistent post-traumatic headache than in controls in both the left-sided m. temporalis (mean ± SD, 157.5 ± 59.9 vs. 201.1 ± 65.2; P < .001) and right-sided m. temporalis (mean ± SD, 159.5 ± 63.8 vs. 212.3 ± 61.9; P < .001). Furthermore, patients with persistent post-traumatic headache also had lower left- and right-sided PPTs in the upper as well as middle part of m. trapezius, compared with healthy controls; all P values were .05 or less., Conclusions: Among patients with persistent post-traumatic headache, pericranial tenderness was more pronounced and PPTs in the head and neck region were lower than in healthy controls free of headache and mild TBI. Further research is needed to better understand the involvement of pericranial myofascial nociceptors in the disease mechanisms underlying post-traumatic headache., (© 2022. The Author(s).)

Background: Posttraumatic headache (PTH) after traumatic brain injury (TBI) is a common clinical symptom, which refers to a headache that occurs after TBI. Acupuncture is often used for the treatment of such patients in China, and significant clinical effects have been achieved. However, to date, its efficacy has not been methodically evaluated. The purpose of this systematic review is to provide evidence to prove the effectiveness of acupuncture in the treatment of PTH in patients with TBI., Methods: This systematic review will be conducted in accordance with the preferred reporting items for systematic review and meta-analysis protocols. The following electronic databases will be searched from their inception to February 2022: PubMed, Web of Science, Embase, PsycINFO, the Cochrane Library, and Chinese databases such as Chinese Biomedical Literature (CBM), Chinese Medical Current Content (CMCC), Chinese Scientific Journal Database (VIP), WanFang Database, and China National Knowledge Infrastructure (CNKI). No language restrictions will be applied to the search strategy. Randomized controlled trials and cohort and case-control studies that met the inclusion and exclusion criteria will be included in this study. The meta-analysis will be performed using RevMan 5.3 software. Each session of this systematic review will be conducted independently by 2 members., Results: This review evaluates the efficacy of acupuncture in the treatment of PTH after TBI., Conclusion: This review provides substantial evidence for the clinical application of acupuncture in PTH treatment after TBI., Ethics and Dissemination: Since the data in this study will be retrieved from published trials, therefore the Patient Consent Statement and Ethical Approval are not required. We will disseminate our results by publishing the research in a peer-reviewed journal., Trail Registration Number: The protocol was registered in INPLASY (INPLASY 202220073)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Post-traumatic headache (PTH) is a common symptom following mild traumatic brain injury (mTBI). Patients at risk to develop acute PTH (aPTH) and further persistent PTH (pPTH) need to be recognized., Methods: This is a one-year follow-up of 127 patients with mTBI, aged 18 to 68, referred to outpatient clinic in the Helsinki University Hospital. Symptoms were assessed at the emergency department (ED), with structured interview at outpatient clinic visit and with Rivermead post-concussion symptom questionnaire at one, three, and 12 months after injury. Psychiatric disorders were assessed with Structured Clinical Interview for DSM-IV Axis I disorders at 3-4 months and return to work (RTW) from patient records., Results: At one month, 77/127 patients (61%) had aPTH. According to multiple logistic regression analysis, risk factors for aPTH were headache at the emergency department (ED) (OR 5.43), other pain (OR 3.19), insomnia (OR 3.23), and vertigo (OR 5.98). At three months, 17 patients (22% of aPTH patients) had developed pPTH, and at one year, 4 patients (24% of pPTH patients) still presented with pPTH. Risk factors for pPTH at three months were older age (OR 1.06) and current insomnia (OR 12.3). The frequency of psychiatric disorders did not differ between the groups. pPTH patients performed worse on their RTW., Conclusions: Risk factors for aPTH were insomnia, headache at ED, other pain, and vertigo and for pPTH, insomnia and older age. RTW rate was lower among pPTH patients., (© 2022. The Author(s).)

Characteristics of persistent post-traumatic headache (PTH) in young individuals are poorly known leading to diagnostic problems and diverse management. We aimed to describe headache phenotypes and self-reported management strategies in young individuals with PTH following mild traumatic brain injury (mTBI). A comprehensive structured questionnaire was used to evaluate headache phenotypes/characteristics and management strategies to relieve headache in 107, 15-30-year-old individuals with PTH. Around 4 months post-injury, migraine-like headache in combination with tension-type like headache (40%) was the most commonly encountered headache phenotype followed by migraine-like headache (36%). Around 50% reported aura-like symptoms before/during the headache attack. Medication-overuse headache was diagnosed in 10%. Stress, sleep disturbances, and bright lights were the most common trigger factors. More than 80% reported that their headache was worsened by work-related activity and alleviated by rest/lying down. Simple analgesics were commonly used (88%) whereas prophylactic drugs were rarely used (5%). Bedrest and physiotherapy were also commonly used as management strategies by 56% and 34% of the participants, respectively. In conclusion, most young individuals with PTH after mTBI presented with combined migraine-like and tension-type-like headache followed by migraine-like headache, only. Preventive headache medication was rarely used, while simple analgesics and bedrest were commonly used for short-term headache relief., (© 2022. The Author(s).)

Traumatic brain injury is a common and major cause of disability and death that might require emergency neurological and neurosurgical interventions. Traumatic brain injury can result in temporary or permanent physical, cognitive and psychological impairments. One of the most common complications associated with traumatic brain injury is post-traumatic headache, associated with significant disability and reduced quality of life. Post-traumatic headache is a public health concern that can affect the long-term outcome of traumatic brain injury patients. Clinical symptoms of post-traumatic headache significantly overlap with common primary headaches such as migraine and tension-type headaches. Beyond neurobiological factors, psychological factors can play crucial roles in the initiation and sustainment of post-traumatic headache. While neurological mechanisms underlying post-traumatic headache remains unknown, different studies suggest various mechanisms such as physical damages to the cranial nerves and neck structure, hyper-sensitization of the pain modulatory pathway, and inflammation as underlying causes for the neurobiology of headache. I explore the hypothesis that traumatic brain injury is associated with headaches. In particular, I provide an overview of the neurobiology of post-traumatic headache, its diagnosis, presenting recent findings on the etiology, explaining similarities and differences between with primary headaches such as migraine and tension-type headache, discuss pharmacological and non-pharmacological interventions for the treatments, as well as emphasising on the psychological importance of post-traumatic headache., Competing Interests: The author declares no conflict of interest., (© 2021 The Author(s). Published by IMR Press.)

Background: Post-traumatic headache (PTH) is a very common symptom following mild traumatic brain injury (mTBI), yet much remains unknown about the underlying pathophysiological mechanisms of PTH. Neuroimaging studies suggest that aberrant functional network connectivity (FNC) may be an important factor in pain disorders. The present study aimed to investigate the functional characteristics of static FNC (sFNC) and dynamic FNC (dFNC) in mTBI patients with PTH., Methods: With Institutional Review Board (IRB) approval, we prospectively recruited 50 mTBI patients with PTH, who were diagnosed with ICHD-3 beta diagnostic criteria and 39 mTBI without PTH who were well matched for age, gender and education. Resting-state functional magnetic resonance imaging (fMRI) scanning (3.0 T, Philips Medical Systems, Netherlands), Montreal Cognitive Assessment (MoCA) and headache symptom measurement (headache frequency and headache intensity) were performed. The resting-state fMRI sequence took 8 min and 10 s. Independent component analysis and sliding window method were applied to examine the FNC on the basis of nine resting-state networks, namely, default mode network (DMN), sensorimotor network (SMN), executive control network (ECN), auditory network (AuN), attention network (AN), salience network (SN), visual network (VN), and cerebellum network (CN). The differences in sFNC and dFNC were determined and correlated with clinical variables using Pearson rank correlation., Results: For sFNC, compared with mTBI patients without PTH, mTB with PTH group showed four altered interactions, including decreased interactions in SN-SMN and VN-DMN pairs, increased sFNC in SN-ECN and SMN-DMN pairs. For dFNC, significant group differences were found in State 2, including increased connectivity alteration in the DMN with CN, DMN with SMN, and AuN with CN. Significant reduced connectivity changes in the DMN with VN was found in State 4. Furthermore, the number of transitions (r=0.394, p=0.005) between states was positively associated with headache frequency. Additionally, dwell time (r=-0.320, p=0.025) in State 1 was negatively correlated with MoCA score., Conclusions: MTBI patients with PTH are characterized with altered sFNC and dFNC, which could provide new perspective to understand the neuropathological mechanism underlying the PTH to determine more appropriate management, and may be a useful imaging biomarker for identifying and predicting mTBI with PTH., (© 2021. The Author(s).)

Background/objective: Changes in speech can be detected objectively before and during migraine attacks. The goal of this study was to interrogate whether speech changes can be detected in subjects with post-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) and whether there are within-subject changes in speech during headaches compared to the headache-free state., Methods: Using a series of speech elicitation tasks uploaded via a mobile application, PTH subjects and healthy controls (HC) provided speech samples once every 3 days, over a period of 12 weeks. The following speech parameters were assessed: vowel space area, vowel articulation precision, consonant articulation precision, average pitch, pitch variance, speaking rate and pause rate. Speech samples of subjects with PTH were compared to HC. To assess speech changes associated with PTH, speech samples of subjects during headache were compared to speech samples when subjects were headache-free. All analyses were conducted using a mixed-effect model design., Results: Longitudinal speech samples were collected from nineteen subjects with PTH (mean age = 42.5, SD = 13.7) who were an average of 14 days (SD = 32.2) from their mTBI at the time of enrollment and thirty-one HC (mean age = 38.7, SD = 12.5). Regardless of headache presence or absence, PTH subjects had longer pause rates and reductions in vowel and consonant articulation precision relative to HC. On days when speech was collected during a headache, there were longer pause rates, slower sentence speaking rates and less precise consonant articulation compared to the speech production of HC. During headache, PTH subjects had slower speaking rates yet more precise vowel articulation compared to when they were headache-free., Conclusions: Compared to HC, subjects with acute PTH demonstrate altered speech as measured by objective features of speech production. For individuals with PTH, speech production may have been more effortful resulting in slower speaking rates and more precise vowel articulation during headache vs. when they were headache-free, suggesting that speech alterations were related to PTH and not solely due to the underlying mTBI., (© 2021. The Author(s).)

Post-traumatic headaches (PTHs) are associated with mild traumatic brain injuries (mTBI) and may predict the persistence of concussion symptoms. Altered brain networks implicated in brain injury and the affective components of headache-related pain may underlie the resolution of PTH. This is a hypothesis-generating investigation to evaluate the extent to which pain symptom reporting and functional brain changes are different in a cohort of young mTBI patients with resolved (PTH-R) and persistent (PTH-P) post-traumatic headache symptoms relative to healthy controls. This was a cross-sectional investigation involving 59 participants between the ages of 12-24 (PTH-P, n  = 21; PTH-R, n  = 18; healthy control, n  = 20). Participants had no significant history of pre-existing headaches, chronic pain, or psychiatric neurological conditions. The primary outcome was resting-state functional connectivity (RS-Fc) alterations between cohorts. Secondary outcomes were self-reported pain-related symptoms. Elevated scores were reported for fear of pain in both PTH cohorts. Using a false discovery rate of p  = 0.05, the PTH-P cohort showed altered connectivity relative to healthy controls in brain regions such as the frontal, temporal, and cerebellar regions, as well as sub-cortical regions including the amygdala and accumbens. The PTH-R cohort showed altered RS-Fc between cerebellar and temporal lobe sub-regions. Our results indicate that a core network of brain regions implicated in the affective pain response are functionally altered in PTH cohorts. Results should be interpreted given limitations on sample size and multiple comparisons. Despite the resolution of symptoms, persons who experience PTH may experience ongoing functional brain abnormalities, which may underlie symptom chronification.

Introduction: Post-traumatic headache (PTH), a common type of headache secondary to traumatic brain injury (TBI) or whiplash, carries a relevant burden on patients. PTH is still an undertreated condition because of limited pharmacological treatment options. Therefore, multimodal non-pharmacologic approaches, which account for comorbidities and biopsychosocial factors, are often used in PTH patients., Areas Covered: After providing a brief overview of PTH, a systematic review was conducted, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations on recently published (2015-2020) papers on non-pharmacological interventions for PTH. We also collected data on ongoing trials on this topic. Studies and results are reviewed and discussed., Expert Opinion: PTH is one of the most common complications of TBI and accounts for almost 4% of symptomatic headache disorders. The most common clinical presentations of PTH are migraine-like or tension type (TTH)-like headache, neck pain, cognitive complaints, and psychological/psychiatric symptoms. Growing evidence suggests that combined pharmacological and non-pharmacological interventions, encompassing noninvasive neuromodulation, physical therapy, cognitive-behavioral treatment, and education, may be the best approaches for PTH and related comorbidities. Acute/preemptive pharmacological treatments for PTH include drugs used for migraine and TTH. When PTH management is multidisciplinary, the patient benefits most.

Headache after craniocerebral injury is an urgent problem due to its frequent occurrence, tendency towards chronization, and strong patient disadaptation effect. Despite the significant incidence of post-traumatic headache (the PTHA) and related socioeconomic factors, many fundamental aspects of this problem have not been considered adequately. Therefore, the aim of our review is to highlight key points regarding the pathogenetic mechanisms of development, key clinical features, and strategies for optimal management of PTHA. A literature review was performed using the Pubmed database by selecting articles about post-traumatic headache (PTHA) over 10 years (from 2010 to 2020).The search was performed in English, Russian, and Ukrainian using the following key words and terms: post-traumatic headache, post-traumatic cephalalgia, headache after brain injury, and post-concussion syndrome. All articles with information on etiology, pathogenesis, clinic, diagnosis, differential diagnosis, neuroimaging, pathomorphological evaluation, and treatment strategies for this pathology were included in the analysis. After identifying all the articles that met the inclusion criteria and deleting duplicate data, 46 literature sources on PTHA were selected. According to the International Headache Classification, PTHA is a secondary cephalalgia associated with head and/or neck injury, which develops within 7 days of a craniocerebral injury. A distinction is made between acute and persistent PTHA associated with mild, moderate, and severe injury. To diagnose persistent PTHA, it is sufficient to establish a causal link between the fact of head injury and the duration of pain for 3+ months. It is interestingly that individuals with mild craniocerebral injury have both higher incidence and higher duration and intensity of PTHA compared to those with severe injury. Despite the absence of specific characteristics, several clinical phenotypes of PTHA are distinguished, the most common of which are migraine-like and tensor types. The pathogenetic mechanisms of PTHA development are complex and diverse. Since recently, special attention has been paid to activation of the trigemino-vasculo-thalamic system, central sensitization, and GCRP-associated mechanisms that probably play an important role in the PTHA pathogenesis. Modern neuroimaging methods using diffusion-tensor and functional MRI are important in the PTHA diagnosis and differential diagnosis. PTHA treatment requires a multidisciplinary approach and includes a combination of drug and drug-free methods. Despite a long history of PTHA research, the issues concerning diagnostic criteria, pathogenetic mechanisms, clinical features, and strategies, in particular in patients who suffered severe craniocerebral injury, have not been considered properly. The above data indicate the need to clarify many aspects of the studied problem.

Background: Post-traumatic headache (PTH) is one of the most common and long-lasting symptoms following mild traumatic brain injury (TBI). However, the pathological mechanisms underlying the development of persistent PTH remain poorly understood. The primary purpose of this prospective pilot study was to evaluate whether early pain modulatory profiles (sensitization and endogenous pain inhibitory capacity) and psychological factors after mild TBI predict the development of persistent PTH in mild TBI patients., Methods: Adult mild TBI patients recruited from Level I Emergency Department Trauma Centers completed study sessions at 1-2 weeks, 1-month, and 4-months post mild TBI. Participants completed the following outcome measures during each session: conditioned pain modulation to measure endogenous pain inhibitory capacity, temporal summation of pain and pressure pain thresholds of the head to measure sensitization of the head, Pain Catastrophizing Scale, Center for Epidemiological Studies - Depression Scale, and a standardized headache survey. Participants were classified into persistent PTH (PPTH) and no-PPTH groups based on the 4-month data., Results: The results revealed that mild TBI patients developing persistent PTH exhibited significantly diminished pain inhibitory capacity, and greater depression and pain catastrophizing following injury compared to those who do not develop persistent PTH. Furthermore, logistic regression indicated that headache pain intensity at 1-2 weeks and pain inhibitory capacity on the conditioned pain modulation test at 1-2 weeks predicted persistent PTH classification at 4 months post injury., Conclusions: Overall, the results suggested that persistent PTH is characterized by dysfunctional alterations in endogenous pain modulatory function and psychological processes in the early stages following mild TBI, which likely exacerbate risk for the maintenance of PTH.

Background: Persistent post-traumatic headache (PTH) is a common sequela of mild traumatic brain injury (TBI) and retrospective assessments have found a migraine-like phenotype to be very frequent. This has raised a discussion of shared underlying mechanisms and whether persistent PTH is simply trauma-triggered migraine., Methods: A 28-day prospective diary study with daily entries and acquisition of data on headache characteristics, associated symptoms, and acute medication use. A total of 64 patients with persistent PTH were enrolled from April 2019 to August 2019. Outcomes were the proportion of monthly headache days of any intensity that met the criteria for a migraine-like day or TTH-like day, as well as the corresponding figures for monthly headache days of moderate to severe intensity. Headache phenotypes were initially assigned based on diagnostic evaluation by semi-structured interview, whilst final headache phenotypes were assigned by diary review., Results: After diary review, we found that monthly headache days were exclusively migraine-like in 24 of 64 patients (38%) and exclusively TTH-like days in 8 of 64 patients (13%). Considering only monthly headache days of moderate to severe intensity, the corresponding figures were 35 of 64 patients (55%) for migraine-like days and 8 of 64 patients (13%) for TTH-like days. The following headache phenotypes were assigned based on diary review: chronic migraine-like (n = 47, 73%), combined episodic migraine-like and chronic TTH-like (n = 9, 13%), and 'pure' chronic TTH-like (n = 8, 13%)., Conclusions: A migraine-like phenotype is common in patients most adversely affected by persistent PTH, although some patients did have a pure chronic TTH-like phenotype. At minimum, these findings suggest that persistent PTH is - at least in some - not 'trauma-triggered migraine'.

Background: According to the International Classification of Headache Disorders 3, post-traumatic headache (PTH) attributed to traumatic brain injury (TBI) is a secondary headache reported to have developed within 7 days from head injury, regaining consciousness following the head injury, or discontinuation of medication(s) impairing the ability to sense or report headache following the head injury. It is one of the most common secondary headache disorders, and it is defined as persistent when it lasts more than 3 months., Main Body: Currently, due to the high prevalence of this disorder, several preclinical studies have been conducted using different animal models of mild TBI to reproduce conditions that engender PTH. Despite representing a simplification of a complex disorder and displaying different limitations concerning the human condition, animal models are still a mainstay to study in vivo the mechanisms of PTH and have provided valuable insight into the pathophysiology and possible treatment strategies. Different models reproduce different types of trauma and have been ideated in order to ensure maximal proximity to the human condition and optimal experimental reproducibility., Conclusion: At present, despite its high prevalence, PTH is not entirely understood, and the differential contribution of pathophysiological mechanisms, also observed in other conditions like migraine, has to be clarified. Although facing limitations, animal models are needed to improve understanding of PTH. The knowledge of currently available models is necessary to all researchers who want to investigate PTH and contribute to unravel its mechanisms.

Background: Calcitonin gene-related peptide (CGRP) has recently been implicated in the pathogenesis of post-traumatic headache (PTH), which raises the prospect for therapeutic use of monoclonal antibodies targeting CGRP or its receptor. Therefore, we decided to assess the efficacy, tolerability, and safety of erenumab for prevention of persistent PTH attributed to mild traumatic brain injury., Methods: A single-center, non-randomized, single-arm, open-label study of erenumab for adults aged 18-65 years with persistent PTH. Patients were assigned to receive 140-mg erenumab monthly by two subcutaneous 1-mL injections, given every 4 weeks for 12 weeks. The primary outcome measure was the mean change in number of monthly headache days of moderate to severe intensity from baseline (4-week pretreatment period) to week 9 through 12. Tolerability and safety endpoints were adverse events (i.e. number and type)., Results: Eighty-nine of 100 patients completed the open-label trial. At baseline, the mean monthly number of headache days of moderate to severe intensity was 15.7. By week 9 through 12, the number was reduced by 2.8 days. The most common adverse events were constipation (n = 30) and injection-site reactions (n = 15). Of 100 patients who received at least one dose of erenumab, two patients discontinued the treatment regimen due to adverse events., Conclusions: Among patients with persistent PTH, erenumab resulted in a lower frequency of moderate to severe headache days in this 12-week open-label trial. In addition, erenumab was well-tolerated as discontinuations due to adverse events were low. Placebo-controlled randomized clinical trials are needed to adequately evaluate the efficacy and safety of erenumab in patients with persistent PTH., Trial Registration: ClinicalTrials.Gov, NCT03974360. Registered on April 17, 2019 - Retrospectively registered.

Objectives: Neck pain commonly accompanies recurrent headaches such as migraine, tension-type and cervicogenic headache. Neck pain may be part of the headache symptom complex or a local source. Patients commonly seek neck treatment to alleviate headache, but this is only indicated when cervical musculoskeletal dysfunction is the source of pain. Clinical presentation of reduced cervical extension, painful cervical joint dysfunction and impaired muscle function collectively has been shown to identify cervicogenic headache among patients with recurrent headaches. The pattern's validity has not been tested against the 'gold standard' of controlled diagnostic blocks. This study assessed the validity of this pattern of cervical musculoskeletal signs to identify a cervical source of headache and neck pain, against controlled diagnostic blocks, in patients with headache and neck pain., Design: Prospective concurrent validity study that employed a diagnostic model building approach to analysis., Setting: Hospital-based multidisciplinary outpatient clinic in Joliet, Illinois., Participants: A convenience sample of participants who presented to a headache clinic with recurrent headaches associated with neck pain. Sixty participants were enrolled and thirty were included in the analysis., Outcome Measures: Participants underwent a clinical examination consisting of relevant tests of cervical musculoskeletal dysfunction. Controlled diagnostic blocks of C2/C3-C3/C4 established a cervical source of neck pain. Penalised logistic regression identified clinical signs to be included in a diagnostic model that best predicted participants' responses to diagnostic blocks., Results: Ten of thirty participants responded to diagnostic blocks. The full pattern of cervical musculoskeletal signs best predicted participants' responses (expected prediction error = 0.57) and accounted for 65% of the variance in responses., Conclusions: This study confirmed the validity of the musculoskeletal pattern to identify a cervical source of headache and neck pain. Adopting this criterion pattern may strengthen cervicogenic headache diagnosis and inform differential diagnosis of neck pain accompanying migraine and tension-type headache., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Headaches and pain-related symptoms are the most disabling somatic complaints following mild traumatic brain injury (mTBI). In this study, we reviewed the existing literature examining structural differences in brain morphology and axonal connections, as well as functional differences in brain activity and connectivity associated with pain or post-traumatic headache (PTH) following mTBI. We searched MEDLINE ® , Embase, PubMed, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials, and Web of Science databases for: (1) TBI OR concussion OR post-concussion syndrome; (2) pain OR headache; and (3) magnetic resonance imaging OR functional MRI OR diffusion tensor imaging. Inclusion criteria were that articles be original studies written in English about participants with mTBI or concussion diagnosis with results reported about pain and/or headache. Excluded were review articles, case studies, documentaries, and studies related to moderate to severe TBI. Quality was assessed using the Newcastle-Ottawa Scale (NOS) quality assessment tool. Nineteen out of 3439 studies satisfied the inclusion and exclusion criteria. Participants with pain-related symptoms had lower cortical thickness in frontal and parietal cortical areas and spinothalamic tract volume. Differences in axonal connectivity were displayed in the corpus callosum, spinothalamic tract, fornix-septohippocampal circuit, and periaqueductal gray. Less activation in pain-related regions during a heat-pain task-based fMRI was reported in participants with PTH. In conclusion, individuals with pain following mTBI display differences in brain structure and brain function, suggesting irregularities in the descending pain modulatory system. These findings primarily provide information on neuroimaging differences in adults; there is limited research in pediatric populations.

Introduction: Traumatic brain injury (TBI) is a major public health concern. Persistent post-traumatic headache (PTH) is a common consequence of TBI affecting productivity and quality of life. The only review providing information about headache prevalence after TBI was published in 2008, combined data from civilian and military TBI, and was strictly derived from Medline database. Due to recent changes in TBI diagnosis and trauma epidemiology, the aim of the current study is to perform a systematic review and meta-analysis to derive updated prevalence estimates of persistent PTH in adult civilian TBI., Methods and Analysis: The methods have been defined following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies published from 2008 to 2019 will be identified searching the electronic databases Medline, Embase, Cochrane, Google Scholar, Directory of Open Access Journals and Web of Science. Retrieved records will be independently screened by two authors and relevant data will be extracted from studies reporting data on persistent PTH prevalence among civilian TBI individuals (≥16 years). The pooled prevalence estimates of any form of headache will be computed applying random-effects meta-analysis. Heterogeneity will be assessed using the I 2 statistic and explored through subgroup analyses considering TBI severity (mild vs moderate/severe). Estimations of risk of bias will be performed using the Risk of Bias Tool for Prevalence Studies., Ethics and Dissemination: The result of this systematic review will be published in a peer-reviewed journal and disseminated at relevant conferences presentations. Formal ethical approval is not required because we will search and evaluate only existing sources of literature. By focusing on studies conducted in the last decade, this review will provide the most up-to-date information about the global prevalence of persistent PTH after TBI. Considering the economical and social burden of persistent PTH after TBI, accurate estimates of this problematic disorder is of utmost importance for planning, implementing and evaluating prevention interventions., Prospero Registration Number: CRD42018094138., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Post-traumatic headache (PTH) is a highly disabling secondary headache disorder and one of the most common sequelae of mild traumatic brain injury, also known as concussion. Considerable overlap exists between PTH and common primary headache disorders. The most common PTH phenotypes are migraine-like headache and tension-type-like headache. A better understanding of the pathophysiological similarities and differences between primary headache disorders and PTH could uncover unique treatment targets for PTH. Although possible underlying mechanisms of PTH have been elucidated, a substantial void remains in our understanding, and further research is needed. In this Review, we describe the evidence from animal and human studies that indicates involvement of several potential mechanisms in the development and persistence of PTH. These mechanisms include impaired descending modulation, neurometabolic changes, neuroinflammation and activation of the trigeminal sensory system. Furthermore, we outline future research directions to establish biomarkers involved in progression from acute to persistent PTH, and we identify potential drug targets to prevent and treat persistent PTH.

Most patients with primary headache disorders identify environmental stimuli (e.g., visual glare), situational factors (e.g., stress), physiological states (e.g., hormones), or activities (e.g., exercise) as triggers that elicit or worsen headache episodes. Headache triggers have not been previously studied in post-traumatic headache (PTH). The present study explored the frequency of headache triggers and their avoidance in PTH. Participants with mild traumatic brain injury (TBI) were recruited from outpatient specialty clinics and completed questionnaires at or soon after their initial clinic visit. The research assessment included a list of 12 possible headache triggers where participants were asked to rate sensitivity (how often they get a headache when exposed to the trigger) and avoidance (how often they try to avoid the trigger). Enrolled participants were 40.6 years old (standard deviation [SD] = 11.8 years) on average, predominantly female (69.8%) and Caucasian (69.8%), and injured in a motor vehicle crash (47.2%) or fall (20.8%). They were assessed at 9.4 weeks (SD = 6.8) post-injury. Most patients with mild TBI in this consecutive series (82.7%) reported ongoing headaches. Mental exertion, stress, and lack of sleep were rated as the most potent headache triggers and among the most frequently avoided. Odors or foods, hunger, and weather conditions were rated as the least potent triggers. Headache trigger sensitivity and avoidance were moderately correlated (r = 0.736, p  < 0.001). Headache severity was more associated with trigger sensitivity [F(2,49) = 13.45, p  < 0.001] than trigger avoidance [F(2,47) = 2.97, p  = 0.062]. In summary, the pattern of headache triggers in persistent PTH after mild TBI appears somewhat different from that in primary headache disorders, with mental exertion emerging as uniquely important. Pervasive avoidance of mental exertion to prevent headaches (cogniphobia) might be a worthwhile behavioral intervention target after mild TBI.

Background: The facet joints contribute to chronic cervical spine pain in an estimated 55% of chronic neck pain cases and can be treated with percutaneous radiofrequency neurotomy (PRN). Damage to surrounding structures during treatment or successful treatment of the primary pain source leading to unmasking could lead to new onset of pain, including cervicogenic headache (CGH). In this study, we aimed to define the incidence of headache in patients who have been previously treated with PRN for lower cervical facet pain., Setting: All patients treated at a single academic institution's pain management clinic from 2014 to 2016 with cervical PRN were reviewed., Methods: All patients treated at a single institution's pain management clinic from 2014 to 2016 were reviewed. Those treated with lower cervical PRN were identified, and incidence of CGH was described as a percentage of the study population. Patient age and pain scores between those with and without headaches following treatment were compared by unpaired T-tests. Gender, presence of comorbid disease and levels involved, quality of pain, exacerbating and alleviating factors, location of referred pain, and previous treatments between those with and without headaches following treatment were compared using chi-square tests., Results: Among the 88 patients in the study group, 12 were found to have only moderate relief of their pretreatment pain as well as a new onset headache meeting the diagnostic criteria for cervicogenic headache. Compared to those without a headache after treatment, those diagnosed with cervicogenic headache were more likely to be female (P = 0.041), report a higher maximum pain level on presentation (P = 0.015), have a diagnosis of diabetes prior to presentation (P = 0.011), and have had the procedure performed at levels which included C3 (P = 0.013) (Table 1)., Limitations: The limitations of this study include its single-center design, as this cohort may not be truly representative of the population of patients receiving cervical PRN as a whole, and as a result, these results may not be generalizable. Due to the small size of the cohort, more subtle differences in presenting signs and symptoms between those with and without headaches may not be detectable. Finally, as previously mentioned, the lack of data on some of the patients who presented with headache may have led to underdiagnosis of the true incidence of cervicogenic headache. Future work should look to re-examine the incidence of CGH in a larger cohort to validate the findings here and further define risk factors for post-procedural CGH., Conclusions: This retrospective review of all patients seen over 2 years in an academic pain clinic found a 13.6% incidence of cervicogenic headache following cervical radiofrequency neurotomy at levels C3-C7. This supports the possibility of the unmasking phenomenon following the procedure, though contributing mechanisms underlying this phenomenon may be multifactorial and require further study.IRB: This study was approved by the institution's Institutional Review Board (IRB2010601795)., Key Words: Cervical spine, facetogenic pain, percutaneous radiofrequency neurotomy, cervicogenic headache, chronic pain, zygapophysial joints, innervation convergence, retrospective chart review.

Background: No evidence is available on the risks of neurologically asymptomatic minimal traumatic intracranial hemorrhage (mTIH) in patients with traumatic brain injury (TBI) for post-traumatic headache (PTH). The purpose of this study was to investigate whether mTIH in patients with TBI was associated with PTH and to evaluate its risk factors., Methods: Between September 2009 and December 2014, 1484 patients with TBI were treated at our institution, 57 of whom had mTIH after TBI and were include in this study. We performed propensity score matching to establish a control group among the 823 patients with TBI treated during the same period. Patients with TBI rated their headaches prospectively using a numeric rating scale (NRS). We compared NRS scores between mTIH group (n = 57) and non-mTIH group (n = 57) and evaluated risk factors of moderate-to-severe PTH (NRS ≥ 4) at the 12-month follow-up., Results: Moderate-to-severe PTH was reported by 21.9% of patients (29.8% in mTIH group and 14.0% in non-mTIH group B, p = 0.012) at the 12-month follow-up. The mean NRS was higher in mTIH group than in non-mTIH group throughout the follow-up period (95% confidence interval [CI], 0.11 to 1.14; p < 0.05, ANCOVA). Logistic regression analysis showed that post-traumatic seizure (odds ratio, 1.520; 95% CI, 1.128-6.785; p = 0.047) and mTIH (odds ratio, 2.194; 95% CI, 1.285-8.475; p = 0.039) were independently associated with moderate-to-severe PTH at the 12-month follow-up., Conclusions: Moderate-to-severe PTH can be expected after TBI in patients with mTIH and post-traumatic seizure. PTH occurs more frequently in patients with mTIH than in those without mTIH.

Cogniphobia refers to avoidance of mental exertion out of a fear of developing or exacerbating a headache. Headaches are very common after mild traumatic brain injury (mTBI) and often become chronic. Cogniphobia is hypothesized to contribute to poor cognitive test performance and persistent disability in some patients with mTBI. Eighty patients with mTBI and post-traumatic headaches were recruited from specialty outpatient clinics. They completed a battery of questionnaires (including a cogniphobia scale) and neuropsychological tests (the National Institutes of Health Toolbox Cognition Battery and the Medical Symptom Validity Test) at 2-3 months post injury, in a cross-sectional design. Participants with more severe headaches reported higher levels of cogniphobia. Cogniphobia was associated with lower performance on memory testing (but not other cognitive tests), independent of headache severity. Participants who avoided mental exertion also tended to avoid physical activity and traumatic stress triggers. The findings provide preliminary support for the role of cogniphobia in persistent cognitive difficulties after mTBI, and suggest that cogniphobia may reflect a broader avoidant coping style.

Headache is one of the most frequently reported symptoms following traumatic brain injury (TBI). Little is known about how these headaches change over time. We describe the natural history of headache in individuals with moderate to severe TBI over 5 years after injury. A total of 316 patients were prospectively enrolled and followed at 3, 6, 12, and 60 months after injury. Individuals were 72% male, 73% white, and 55% injured in motor vehicle crashes, with an average age of 42. Pre-injury headache was reported in 17% of individuals. New or worse headache prevalence remained consistent with at least 33% at all time points. Incidence was >17% at all time points with first report of new or worse headache in 20% of participants at 60 months. Disability related to headache was high, with average headache pain (on 0-10 scale) ranging from 5.5 at baseline to 5.7 at 60 months post-injury, and reports of substantial impact on daily life across all time points. More than half of classifiable headaches matched the profile of migraine or probable migraine. Headache is a substantial problem after TBI. Results suggest that ongoing assessment and treatment of headache after TBI is needed, as this symptom may be a problem up to 5 years post-injury.

Context: Pediatric concussions are common, and emphasis on correct diagnosis and management is stressed in consensus guidelines. Medications may have a role in management of concussion, but no consensus exists regarding appropriate pharmacologic therapy., Evidence Acquisition: Nonsystematic review., Study Design: Clinical review., Level of Evidence: Level 4., Results: There is limited evidence for hypertonic saline to improve posttraumatic headache in the emergency department setting. There is essentially no evidence for the use of any other medication in management of pediatric sport-related concussion., Conclusion: Further research is necessary to determine whether there is benefit to the use of any pharmacotherapy in the management of pediatric-aged athletes with concussions.

A comparison has been made between the cervicogenic headache criteria in the new IHS classification of headaches (3rd edition-beta version) and The Cervicogenic Headache International Study Group's (GHISG) criteria from 1998. In a more recent version, the CHISG criteria consist of 7 different items. While "core cases" of cervicogenic headache (CEH) usually fulfill all 7 criteria, the IHS classification--3rd edition beta version--fulfills only 3 criteria. Although the new three beta version represents an improvement from the previous one, it does not quite seem to live up to the expectations for a diagnostic system for routine, clinical use.

Objectives: The primary goal of this study was to evaluate the incidence and characteristics of posttraumatic headache attributed to mild brain injury in military personnel in Iran within a prospective and observational study design., Methods: A prospective observational descriptive study was conducted with a cohort of military personnel under military education during a 6-month period at the Military Education Center in Isfahan, Iran. 322 military personnel under education were selected randomly and were given a 13-item mild brain injury questionnaire accompanied with affective disorders and headache questionnaires and were reevaluated after a 3-month interval., Results: A total of 30 (9.3 %) of the 322 military personnel met criteria for a mild brain injury. Among them, 18 personnel (60 %) reported having headaches during the 3-month reevaluation. PTHs defined as headaches beginning within 1 week after a head trauma were present in 5.6 % of military personnel under study during 6 months. In total, 67 % of posttraumatic headaches (PTH) were classified as migrainous or possible migrainous features. Patients with affective disorders such as posttraumatic stress disorder and depression were at a higher risk for developing PTH following mild brain injury (p < 0.05). PTH did not relate to demographic factors such as age or type of trauma., Conclusions: Posttraumatic headache attributed to mild brain injury is a common disorder in military personnel. Migrainous features are predominant among them in comparison with the general population. PTH is not related to a type of trauma, but has association with affective disorders.

Headache is the most frequent reason for referral to an outpatient neurology and pain physician practice, with post-traumatic headache (PTH) accounting for approximately 4% of all symptomatic headaches. Headache following trauma has been reported for centuries. In this unique case report we will discuss the clinical course and successful headache treatment of a 57-year-old man diagnosed with PTHs. He suffered from chronic, intractable headaches resistant to multidisciplinary medical management for 4 years. A trial of electrical neuromodulation of the C2-C3 branches within the great auricular nerve (GAN) distribution was proposed as a potential long-term treatment for his chronic, intractable headaches after having several prior headache attacks successfully aborted with ultrasound-guided GAN blocks. Six months after permanent peripheral neurostimulator implantation, the patient reported a greater than 90% reduction in headache frequency, and was able to wean off all his previous prophylactic and abortive headache medications, with the exception of over-the-counter ibuprofen as needed. Subcutaneous electrode application over the branches of C2-C3-namely greater, lesser, and the least occipital nerves-for the treatment of chronic, intractable headache is not a new concept within pain medicine literature. However, subcutaneous electrode application, specifically over the GAN, is unique. The following case report chronicles the novel application of ultrasound-guided peripheral nerve stimulation of the GAN as an effective and safe long-term treatment for chronic, intractable primary headache. The positive outcome chronicled in this case presentation suggests that peripheral nerve stimulation of the GAN should be considered for highly select cases. To our knowledge, this is the first such case report describing GAN as a target for the management of PTH in the literature.

Purpose: Many studies have indicated that cervicogenic headache may originate from the cervical structures innervated by the upper cervical spinal nerves. To date, no study has investigated whether narrowing of the craniovertebral angle (CVA) or cervicomedullary angle (CMA) affects the three upper cervical spinal nerves. The aim of this study was to investigate the effect of CVA and/or CMA narrowing on the occurrence of cervicogenic headache., Materials and Methods: Two hundred and five patients diagnosed with cervicogenic headache were included in the study. The pain scores of patients were determined using a visual analog scale. The nonheadache control group consisted of 40 volunteers. CVA and CMA values were measured on sagittal T2-weighted magnetic resonance imaging (MRI), on two occasions by two radiologists. Angle values and categorized pain scores were compared statistically between the groups., Results: Intraobserver and interobserver agreement was over 97% for all measurements. Pain scores increased with decreasing CVA and CMA values. Mean angle values were significantly different among the pain categories (P < 0.001). The pain score was negatively correlated with CMA (Spearman correlation coefficient, rs, -0.676; P < 0.001) and CVA values (rs, -0.725; P < 0.001)., Conclusion: CVA or CMA narrowing affects the occurrence of cervicogenic headache. There is an inverse relationship between the angle values and pain scores.

We present a series of four patients with neurological symptoms following head injury. In each case neuroimaging was normal, but careful examination demonstrated altered sensation over the distribution of the supraorbital nerve. We discuss traumatic supraorbital neuralgia and how it differs from the more commonly reported idiopathic form.

This paper aims to investigate the relevance of morphological changes in the main stabilizing structures of the craniocervical junction in persons with cervicogenic headache (CEH). A case control study of 46 consecutive persons with CEH, 22 consecutive with headache attributed to whiplash associated headache (WLaH) and 19 consecutive persons with migraine. The criteria of the Cervicogenic Headache International Study Group (CHISG) were used for diagnosing CEH; otherwise the criteria of the International Classification of Headache Disorders (ICHD II) were applied. All participants had a clinical interview, and physical and neurological examination. Proton weighted magnetic resonance imaging (MRI) of the craniovertebral junction, and the alar and transverse ligaments were evaluated and blinded to clinical information. The MRI of the craniovertebral and the cervical junctions, the alar and transverse ligaments disclosed no significant differences between those with CEH, WLaH and or migraine. The site of CEH pain was not correlated with the site of signal intensity changes of the alar and transverse ligaments. In fact, very few had moderate or severe signal intensity changes in their ligaments. MRI shows no specific changes of cervical discs or craniovertebral ligaments in CEH.

Headache is one of the most common persisting symptoms after traumatic brain injury (TBI). Yet there is a paucity of prospective longitudinal studies of the incidence and prevalence of headache in a sample with a range of injury severity. We sought to describe the natural history of headache in the first year after TBI, and to determine the roles of prior history of headache, sex, and severity of TBI as risk factors for post-traumatic headache. A cohort of 452 acute, consecutive patients admitted to inpatient rehabilitation services with TBI were enrolled during their inpatient rehabilitation from February 2008 to June 2009. Subjects were enrolled across 7 acute rehabilitation centers designated as TBI Model Systems centers. They were prospectively assessed by structured interviews prior to inpatient rehabilitation discharge, and at 3, 6, and 12 months after injury. Results of this natural history study suggest that 71% of participants reported headache during the first year after injury. The prevalence of headache remained high over the first year, with more than 41% of participants reporting headache at 3, 6, and 12 months post-injury. Persons with a pre-injury history of headache (p<0.001) and females (p<0.01) were significantly more likely to report headache. The incidence of headache had no relation to TBI severity (p=0.67). Overall, headache is common in the first year after TBI, independent of the severity of injury range examined in this study. Use of the International Classification of Headache Disorders criteria requiring onset of headache within 1 week of injury underestimates rates of post-traumatic headache. Better understanding of the natural history of headache including timing, type, and risk factors should aid in the design of treatment studies to prevent or reduce the chronicity of headache and its disruptive effects on quality of life.

Rectus capitis posterior muscles are located in the suboccipital triangle and function in extension and lateral rotation of the head and neck. There are two of these muscles on each side: the rectus capitis posterior major and the rectus capitis posterior minor. In the present case we observed bilateral double rectus capitis posterior major muscle and bilateral absence of rectus capitis posterior minor muscle. The additional rectus capitis posterior major may put more strain to the spine of the axis and mean time the bilateral absence of rectus capitis posterior minor muscles will result in muscular in coordination in the suboccipital region while balancing the head. The present variation should be considered in the aetiology of cervicogenic headache.

The International Classification of Headache Disorders does not separate the moderate from severe/very severe traumatic brain injury (TBI), since they are all defined by Glasgow coma scale (GCS) < 13. The distinction between the severe and very severe TBI (GCS < 8) should be made upon coma duration that in the latter may be longer than 15 days up to months in the case of vegetative state. Post-traumatic amnesia duration may double the coma duration itself. Therefore, the 3-month parameter proposed to define the occurrence or resolution of post-traumatic headache (PTH) appears inadequate. Following TBI, neuropathic pain, central pain, thalamic pain, combined pain are all possible and they call for proper pharmacological approaches. One more reason for having difficulties in obtaining information about headache in the early phase after regaining consciousness is the presence of concomitant medications that may affect pain perception. Post-traumatic stress disorder (PTSD) develops days or weeks after stress and tends to improve or disappear within 3 months after exposure; interestingly, this spontaneous timing resembles that of PTH. In our experience the number of TBI patients with PTH at 1-year follow-up is lower in those with longer coma duration and more severe TBI. Cognitive functioning evaluated after at least 12 months from TBI, showed mild or no impairment in these patients with severe TBI and PTH, whereas they have psychopathological changes, namely anxiety and depression. The majority of patients with PTH after severe/very severe TBI had skull fractures or dural lacerations and paroxystic EEG abnormalities. The combination of psychological changes (depression and anxiety) and organic features (skull fractures, dural lacerations, epileptic EEG abnormalities) in PTH may be inversely correlated with the severity of TBI, with prevalence of psychological disturbances in mild TBI and of organic lesions in severe TBI. On the other hand, only in severe TBI patients with good cognitive recovery the influence of the psychopathological disorders may play a role. In fact, the affective pain perception is probably related to the integrity of cognitive functions as in mild TBI and in severe TBI with good cognitive outcome.

The onset of post-traumatic headache (PTC) occurs in the first seven days after trauma, according to the International Headache Society (IHS) classification. The objective of this study was to evaluate the several forms of headache that appear after mild head injury (HI) and time interval between the HI and the onset of pain. We evaluated 41 patients with diagnosis of mild HI following the IHS criteria. Migraine without aura and the chronic tension-type headache were the most prevalent groups, occurring in 16 (39%) and 14 (34.1%) patients respectively. The time interval between HI and the onset of headache was less than seven days in 20 patients (48.7%) and longer than 30 days in 10 (24.3%) patients. The results suggest that PTC may arise after a period longer than is accepted at the present by the IHS.

Objective: To establish the prevalence of post traumatic headache, persisting at 3 months following minor traumatic brain injury., Design: A prospective controlled study of patients admitted with a diagnosis of mild traumatic brain injury and matched orthopedic controls over 12 months during 2004., Setting: A level two inner city Emergency Department in Sydney, Australia., Patients: One hundred eligible sequential admissions with mild traumatic brain injury as defined by American Congress of Rehabilitation Medicine, 1993, and 100 matched minor injury controls with nondeceleration injuries., Interventions: Subjects were part of a study on prediction of postconcussive syndrome and had neuropsychological tests, balance test and pain recordings taken at the time of injury, at 1 month and at 3 months post injury., Outcome Measures: Main measures were the reporting of headache "worse than prior to the injury" and concordant with the definition of Posttraumatic Headache according to International Headache Society Classification of Headache Disorders 2003., Results: 15.34% of those with minor head injury continued to complain of perisistant posttraumatic headache at 3 months compared to 2.2% of the minor injury controls., Conclusions: To the authors' knowledge this is the first controlled prospective study in the prevalence of posttraumatic headache following mild traumatic brain injury.

Since many years we routinely use diagnostic selective nerve root blocks (SNRB) at our department when evaluating patients with cervical radiculopathy. Frequently patients who also presented with headache reported that the headache disappeared when the nerve root responsible for the radicular pain was blocked with local anaesthetics. Headache has been described as a companioning symptom related to cervical radiculopathy but has never before been evaluated with SNRB performed in the lower cervical spine. For this reason we added to our routine an evaluation of the response from the SNRB on headache in patients with cervical radiculopathy. The aim was to describe the frequency of headache in patients with cervical radiculopathy and its response to a selective nerve root block of the nerve root/roots responsible for the radiculopathy. Can nerve root compression in the lower cervical spine produce headache? In this consecutive series of 275 patients with cervical radiculopathy, 161 patients reported that they also suffered from daily or recurrent headache located most often unilaterally on the same side as the radiculopathy. All patients underwent a careful clinical examination by a neurosurgeon and a MRI of the cervical spine. The significantly compressed root/roots, according to the MRI, underwent SNRB with a local anaesthetic. The effect of the nerve root block on the radiculopathy and the headache was carefully noted and evaluated by a physiotherapist using visual analogue scales (VAS) before and after the SNRB. All patients with headache had tender points in the neck/shoulder region on the affected side. Patients with headache graded significantly more limitations in daily activities and higher pain intensity in the neck/shoulder/arm than patients without headache. After selective nerve root block, 59% of the patients with headache reported 50% or more reduction of headache and of these 69% reported total relief. A significant correlation was seen between reduced headache intensity and reduced pain in the neck, shoulder and arm. The result indicates that cervical root compression from degenerative disease in the lower cervical spine producing radiculopathy might also induce headache.