Effects of PDE-3 inhibition in persistent post-traumatic headache: evidence of cAMP-dependent signaling.

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.

Myofascial Release for the Treatment of Tension-Type, Cervicogenic Headache or Migraine: A Systematic Review and Meta-Analysis.

Objective: To assess the effectiveness of myofascial release (MFR) techniques on the intensity of headache pain and associated disability in patients with tension-type headache (TTH), cervicogenic headache (CGH), or migraine. Design: A systematic review and meta-analysis. Methods: Eight databases were searched on September 15, 2023, including PubMed, Scopus, Web of Science, CINAHL, Cochrane Library, Embase, CNKI, and Wanfang Database. The risk of bias was evaluated utilizing the Cochrane Risk of Bias 2 (RoB 2) tool. Results: Pooled results showed that MFR intervention significantly reduces pain intensity [SMD = -2.01, 95% CI (-2.98, -1.03), I2 = 90%, P < 0.001] and improves disability [SMD = -1.3, 95% CI (-1.82, -0.79), I2 = 74%, P < 0.001]. Subgroup analysis based on the type of headache revealed significant reductions in pain intensity for CGH [SMD = -2.01, 95% CI (-2.73, -1.29), I2 = 63%, P < 0.001], TTH [SMD = -0.86, 95% CI (-1.52, -0.20), I2 = 50%, P=0.01] and migraine [SMD = -6.52, 95% CI (-8.15, -4.89), P < 0.001] and in disability for CGH [SMD = -1.45, 95% CI (-2.07, -0.83), I2 = 0%, P < 0.001]; TTH [SMD = -0.98, 95% CI (-1.32, -0.65), I2 = 0%, P < 0.001] but not migraine [SMD = -2.44, 95% CI (-6.04, 1.16), I2 = 97%, P=0.18]. Conclusion: The meta-analysis results indicate that MFR intervention can significantly alleviate pain and disability in TTH and CGH. For migraine, however, the results were inconsistent, and there was only moderate quality evidence of disability improvement for TTH and CGH. In contrast, the quality of other evidence was low or very low.

The Postconcussion Syndrome and Posttraumatic Headaches in Civilians, Soldiers, and Athletes.

Posttraumatic headaches are one of the most common and controversial secondary headache types. After a mild traumatic brain, an estimated 11% to 82% of people develop a postconcussion syndrome, which has been controversial for more than 160 years. Headache is estimated as present in 30% to 90% of patients after a mild head injury. Most headaches are tension-type-like or migraine-like. Headaches in civilians, soldiers, athletes, and postcraniotomy are reviewed. The treatments are the same as for the primary headaches. Persistent posttraumatic headaches can continue for many years.

Cervicogenic Headaches: A Literature Review and Proposed Multifaceted Approach to Diagnosis and Management.

Cervicogenic headaches are a secondary headache disorder attributable to cervical spine dysfunction resulting in head pain with or without neck pain. Diagnosis of this condition has been complicated by varied clinical presentations, causations, and differing diagnostic criteria. In this article, we aim to clarify the approach to diagnosing cervicogenic headaches by providing an overview of cervicogenic headaches, clinical case examples, and a practical diagnostic algorithm based on the most current criteria. A standardized approach will aid in confirmation of the diagnosis of cervicogenic headaches and facilitate further research into this condition.

Guidelines of the International Headache Society for controlled trials of pharmacological preventive treatment for persistent post-traumatic headache attributed to mild traumatic brain injury.

BACKGROUND: Persistent headache attributed to traumatic injury to the head is divided into two subtypes, one attributed to moderate or severe traumatic injury and another attributed to mild traumatic injury (i.e., concussion). The latter is much more prevalent, in part because more than 90% of cases with traumatic brain injury are classified as mild. The pathophysiology of persistent post-traumatic headache is poorly understood and the underlying mechanisms are likely multifactorial. There is currently no approved treatment specifically for persistent post-traumatic headache, and management strategies rely on medications used for migraine or tension-type headache. Therefore, high-quality trials are urgently needed to support clinical decision-making and optimize management strategies. International guidelines can facilitate appropriate trial design and ensure the acquisition of high-quality data evaluating the efficacy, tolerability, and safety of available and novel pharmacological therapies for the preventive treatment of persistent post-traumatic headache. METHODS: The development of this guideline was based on a literature review of available studies in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, along with a review of previously published guidelines for controlled trials of preventive treatment for episodic and chronic migraine. The identified literature was critically appraised, and due to the scarcity of scientific evidence, recommendations were primarily based on the consensus of experts in the field. OBJECTIVE: To provide guidelines for designing state-of-the-art controlled clinical trials aimed at evaluating the effectiveness of preventive treatments for persistent post-traumatic headache attributed to mild traumatic brain injury.

Comparative effectiveness of cervical vs thoracic spinal-thrust manipulation for care of cervicogenic headache: A randomized controlled trial.

BACKGROUND: There is ample evidence supporting the use of different manipulative therapy techniques for Cervicogenic Headache (CgH). However, no technique can be singled as the best available treatment for patients with CgH. Therefore, the objective of the study is to find and compare the clinical effects of cervical spine over thoracic spine manipulation and conventional physiotherapy in patients with CgH. DESIGN, SETTING, AND PARTICIPANTS: It is a prospective, randomized controlled study conducted between July 2020 and January 2023 at the University hospital. N = 96 eligible patients with CgH were selected based on selection criteria and they were divided into cervical spine manipulation (CSM; n = 32), thoracic spine manipulation (TSM; n = 32) and conventional physiotherapy (CPT; n = 32) groups, and received the respective treatment for four weeks. Primary (CgH frequency) and secondary CgH pain intensity, CgH disability, neck pain frequency, neck pain intensity, neck pain threshold, cervical flexion rotation test (CFRT), neck disability index (NDI) and quality of life (QoL) scores were measured. The effects of treatment at various intervals were analyzed using a 3 × 4 linear mixed model analysis (LMM), with treatment group (cervical spine manipulation, thoracic spine manipulation, and conventional physiotherapy) and time intervals (baseline, 4 weeks, 8 weeks, and 6 months), and the statistical significance level was set at P < 0.05. RESULTS: The reports of the CSM, TSM and CPT groups were compared between the groups. Four weeks following treatment CSM group showed more significant changes in primary (CgH frequency) and secondary (CgH pain intensity, CgH disability, neck pain frequency, pain intensity, pain threshold, CFRT, NDI and QoL) than the TSM and CPT groups (p = 0.001). The same gradual improvement was seen in the CSM group when compared to TSM and CPT groups (p = 0.001) in the above variables at 8 weeks and 6 months follow-up. CONCLUSION: The reports of the current randomized clinical study found that CSM resulted in significantly better improvements in pain parameters (intensity, frequency and threshold) functional disability and quality of life in patients with CgH than thoracic spine manipulation and conventional physiotherapy. TRIAL REGISTRATION: Clinical trial registration: CTRI/2020/06/026092 trial was registered prospectively on 24/06/2020.

Serial changes in diffusion tensor imaging metrics and therapeutic effects of repetitive transcranial magnetic stimulation in post-traumatic headache and depression: A case report.

BACKGROUND: Mild traumatic brain injury patients commonly complain headache and central pain, and the pain accompanies depressive mood change. This case study reports the therapeutic effect of repetitive transcranial magnetic stimulation (rTMS) in mild traumatic brain injury patient with headache and depression through objective serial changes of diffusion tensor imaging (DTI). METHODS: The 51-year-old man complained of headache and depression despite conventional treatment for 13 months. We applied 15 times rTMS on the left dorsolateral prefrontal cortex. We checked the pain and depression through numeric rating scale (NRS) and Beck depression inventory (BDI) when admission, discharged, and 1 month after discharge. DTI was performed 3 times; before, during-day of rTMS 6th stimulation, and after-day of rTMS 15th stimulation. Then the reconstructed White matter related to pain and depression was obtained. RESULTS: NRS and BDI showed significant improvement and it was maintained 1 year after discharge. DTI-based metrics of the White matters related to pain and depression gradually increased before - during - after rTMS. CONCLUSION: Studies focused on examining changes in pain, depression and DTI-based metrics of White matter are rare. This case is significant in that not only pain and depression improved after the rTMS, but also serial changes in White matter were observed in DTI.

Effects of sustained natural apophyseal glides versus rocabado 6 × 6 program in subjects with cervicogenic headache.

BACKGROUND: Cervicogenic headache is designated as the most common type of secondary headache that results from conditions affecting the neck's bony components, muscles, and intervertebral discs rather than the head itself. OBJECTIVE: The purpose was to determine the effects of Sustained Natural Apophyseal Glides (SNAGs) versus the Rocabado 6 × 6 program in subjects with cervicogenic headaches. METHODS: This study was a randomized clinical trial. The sample size was 38, and participants aged 20-60 years (mean age 40.22 ± 9.66) suffering from cervicogenic headaches were randomly allocated using the lottery method into two groups with 19 participants in each group. Assessment of subjects was done before starting treatment and by the end of the 8th week for all the variables. Outcome measures were the Neck Disability Index (NDI), 6-item Headache Impact Test (HIT-6), Flexion-Rotation test (FRT) to assess the rotation range of motion at the level of C1-C2 (goniometer) and the Numeric Pain Rating Scale (NPRS) for the intensity of pain. Data analysis was done by SPSS (IBM) 25. To check the normality of the data the Shapiro-Wilk test was used. RESULTS: In the Shapiro-Wilk test p-value of all the testing variables i.e. NDI, HIT-6 score, FRT and NPRS was > 0.05, data was normally distributed and parametric tests were used. Group A showed a considerable improvement (p < 0.05) in all variables compared to Group B, while within-group analysis of both groups shows that all outcome measures show significant results (p < 0.05). CONCLUSION: It was concluded that both SNAGs and Rocabado's 6 × 6 exercises were effective for the treatment of cervicogenic headache but the effects of headache SNAG were superior and produced more improvement in intensity of headache, disability, frequency of headache, duration of headache as compared to Rocabado 6 × 6 exercises. TRIAL REGISTRATION NUMBER: This study was registered at ClinicalTrials.gov ID: NCT05865808 on date 19/05/2023.

Massage for neck pain.

BACKGROUND: Massage is widely used for neck pain, but its effectiveness remains unclear. OBJECTIVES: To assess the benefits and harms of massage compared to placebo or sham, no treatment or exercise as an adjuvant to the same co-intervention for acute to chronic persisting neck pain in adults with or without radiculopathy, including whiplash-associated disorders and cervicogenic headache. SEARCH METHODS: We searched multiple databases (CENTRAL, MEDLINE, EMBASE, CINAHL, Index to Chiropractic Literature, trial registries) to 1 October 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing any type of massage with sham or placebo, no treatment or wait-list, or massage as an adjuvant treatment, in adults with acute, subacute or chronic neck pain. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. We transformed outcomes to standardise the direction of the effect (a smaller score is better). We used a partially contextualised approach relative to identified thresholds to report the effect size as slight-small, moderate or large-substantive. MAIN RESULTS: We included 33 studies (1994 participants analysed). Selection (82%) and detection bias (94%) were common; multiple trials had unclear allocation concealment, utilised a placebo that may not be credible and did not test whether blinding to the placebo was effective. Massage was compared with placebo (n = 10) or no treatment (n = 8), or assessed as an adjuvant to the same co-treatment (n = 15). The trials studied adults aged 18 to 70 years, 70% female, with mean pain severity of 51.8 (standard deviation (SD) 14.1) on a visual analogue scale (0 to 100). Neck pain was subacute-chronic and classified as non-specific neck pain (85%, including n = 1 whiplash), radiculopathy (6%) or cervicogenic headache (9%). Trials were conducted in outpatient settings in Asia (n = 11), America (n = 5), Africa (n = 1), Europe (n = 12) and the Middle East (n = 4). Trials received research funding (15%) from research institutes. We report the main results for the comparison of massage versus placebo. Low-certainty evidence indicates that massage probably results in little to no difference in pain, function-disability and health-related quality of life when compared against a placebo for subacute-chronic neck pain at up to 12 weeks follow-up. It may slightly improve participant-reported treatment success. Subgroup analysis by dose showed a clinically important difference favouring a high dose (≥ 8 sessions over four weeks for ≥ 30 minutes duration). There is very low-certainty evidence for total adverse events. Data on patient satisfaction and serious adverse events were not available. Pain was a mean of 20.55 points with placebo and improved by 3.43 points with massage (95% confidence interval (CI) 8.16 better to 1.29 worse) on a 0 to 100 scale, where a lower score indicates less pain (8 studies, 403 participants; I2 = 39%). We downgraded the evidence to low-certainty due to indirectness; most trials in the placebo comparison used suboptimal massage doses (only single sessions). Selection, performance and detection bias were evident as multiple trials had unclear allocation concealment, utilised a placebo that may not be credible and did not test whether blinding was effective, respectively. Function-disability was a mean of 30.90 points with placebo and improved by 9.69 points with massage (95% CI 17.57 better to 1.81 better) on the Neck Disability Index 0 to 100, where a lower score indicates better function (2 studies, 68 participants; I2 = 0%). We downgraded the evidence to low-certainty due to imprecision (the wide CI represents slight to moderate benefit that does not rule in or rule out a clinically important change) and risk of selection, performance and detection biases. Participant-reported treatment success was a mean of 3.1 points with placebo and improved by 0.80 points with massage (95% CI 1.39 better to 0.21 better) on a Global Improvement 1 to 7 scale, where a lower score indicates very much improved (1 study, 54 participants). We downgraded the evidence to low-certainty due to imprecision (single study with a wide CI that does not rule in or rule out a clinically important change) and risk of performance as well as detection bias. Health-related quality of life was a mean of 43.2 points with placebo and improved by 5.30 points with massage (95% CI 8.24 better to 2.36 better) on the SF-12 (physical) 0 to 100 scale, where 0 indicates the lowest level of health (1 study, 54 participants). We downgraded the evidence once for imprecision (a single small study) and risk of performance and detection bias. We are uncertain whether massage results in increased total adverse events, such as treatment soreness, sweating or low blood pressure (RR 0.99, 95% CI 0.08 to 11.55; 2 studies, 175 participants; I2 = 77%). We downgraded the evidence to very low-certainty due to unexplained inconsistency, risk of performance and detection bias, and imprecision (the CI was extremely wide and the total number of events was very small, i.e < 200 events). AUTHORS' CONCLUSIONS: The contribution of massage to the management of neck pain remains uncertain given the predominance of low-certainty evidence in this field. For subacute and chronic neck pain (closest to 12 weeks follow-up), massage may result in a little or no difference in improving pain, function-disability, health-related quality of life and participant-reported treatment success when compared to a placebo. Inadequate reporting on adverse events precluded analysis. Focused planning for larger, adequately dosed, well-designed trials is needed.

Serum calcitonin gene-related peptide in patients with persistent post-concussion symptoms, including headache: a cohort study.

BACKGROUND: Calcitonin gene-related peptide (CGRP) plays an important role in migraine pathophysiology, and post-traumatic headache (PTH) frequently presents with migraine-like features. Despite several clinical similarities, few studies have explored CGRP in PTH and concussion. This study investigates serum CGRP levels in patients with persistent post-concussion symptoms (PPCS), including PTH. METHODS: This cohort study was based on serum samples from individuals aged 18-30 years with PPCS who participated in a previously published randomized controlled trial of a non-pharmacological intervention. The primary outcome was serum CGRP concentrations, determined at baseline before randomization and at follow-up 7 months later, using an enzyme-linked immunosorbent assay (ELISA). CGRP levels at baseline were compared with healthy anonymous blood donors in the same age group. RESULTS: Baseline serum samples were collected from 86 participants with PPCS. The participants were most often female (78%) and migraine-like headache was the most frequent headache phenotype (74%). Serum CGRP levels were higher in participants with PPCS than in 120 healthy individuals (median: 158.5 pg/mL vs. 76.3 pg/mL, p = 0.050). A stratified analysis revealed that females with PPCS had a fivefold higher median than healthy females (166.3 pg/mL vs. 32.1 pg/mL, p = 0.0006), while no differences were observed in males (p = 0.83). At follow-up, CGRP levels decreased with a median change of - 1.3 pg/mL (95% confidence interval: - 17.6-0, p = 0.024). DISCUSSION: Elevated serum levels of CGRP in patients with PPCS and a decrease over time suggest an involvement of CGRP in PTH/PPCS. If confirmed in other studies, it could pave the way for CGRP-targeted therapies, which could have clinical significance.

Posttraumatic headache is a distinct headache type from migraine.

PURPOSE OF REVIEW: Posttraumatic headache (PTH), a headache that develops within 7 days of a causative injury, is one of the most common secondary headaches, mostly attributed to mild traumatic brain injury (mTBI). Because presence of preinjury headache is a risk factor for developing PTH and PTH symptoms often resemble migraine or tension-type headache, the association between PTH and primary headaches has attracted attention from clinicians and scientists. RECENT FINDINGS: Recent studies on epidemiological aspects, headache features, risk factors, imaging characteristics, and response to treatment, suggest overlapping features and distinct objective findings in PTH compared to migraine. SUMMARY: We argue that PTH is distinct from migraine. Therefore, PTH epidemiology, pathophysiology, diagnosis, treatment, and prognosis should continue to be investigated separately from migraine.

Cross-cultural adaptation, reliability and validity of the Turkish version of the Henry Ford Hospital Headache Disability Inventory (HDI/T) in patients with cervicogenic headache.

PURPOSE: Cultural adaptation to Henry Ford Hospital Headache Disability Inventory (HDI) and investigating the validity and reliability of this inventory. METHODS: International standards were followed in conducting the cultural adaption of Henry Ford Hospital Headache Disability Inventory Turkish version (HDI-T). Test-Retest reliability (intraclass correlation coefficient, ICC) and internal consistency (Cronbach's alpha) were included in the psychometric assessments; Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to assess the structural validity; and construct validity was performed by examining relationship the HDI-T between the Headache Impact Test-6 (HIT- 6), Neck Disability Index (NDI), Perceived Stress Scale-14 (PSS-14), and Nottingham Health Profile (NHP). RESULTS: HDI-T showed excellent test-retest reliability (ICC =0.901), excellent internal consistency (Cronbach's a = 0.935), and low to high correlation with Headache Impact Test-6 (HIT-6), Neck Disability Index (NDI), Perceived Stress Scale-14 (PSS-14) and Nottingham Health Profile (NHP). Following EFA, two factors (emotional and functional) were extracted, accounting for 50.734% of the total variation. The dimensional structure of the HDI-T obtained in the EFA was confirmed by CFA. CONCLUSION: The HDI-T is a reliable and valid instrument to determine the symptoms and disability in the Turkish population with cervicogenic headaches.Implications for RehabilitationHenry Ford Hospital Headache Disability Inventory Turkish version (HDI-T) is an outcome measure with high validity and reliability to obtain objective data in the determination of disability due to cervicogenic headache.HDI-T is recommended for all rehabilitation professionals to evaluate both the disability levels before rehabilitation and the changes during the rehabilitation process in patients with cervicogenic headaches in the Turkish population.Physiotherapists, orthopedists and neurosurgeons can also use HDI-T to objectively evaluate the secondary effects of their treatment for neck problems.

Physical Therapist Interventions to Reduce Headache Intensity, Frequency, and Duration in Patients With Cervicogenic Headache: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: The aim of this study was to assess the efficacy of physical therapist interventions on the intensity, frequency, and duration of headaches, as well as on the quality of life of patients with cervicogenic headache. METHODS: The following databases were searched up to October 2022: Physiotherapy Evidence Database, Web of Science, Pubmed, and Cochrane Library. Randomized controlled trials assessing the effect of physical therapist interventions on adults with cervicogenic headache were included. Quality appraisal was conducted using the Cochrane risk of bias 2.0 tool and the Confidence in Network Meta-analysis web app. Synthesis methods were conducted in accordance with the Cochrane Handbook. RESULTS: Of the 28 identified reports, 23 were included in the quantitative synthesis. Manipulation plus dry needling was the highest-ranked intervention to reduce the short-term headache intensity (mean difference [MD] = -4.87; 95% CI = -8.51 to -1.24) and frequency (MD = -3.09; 95% CI = -4.93 to -1.25) when compared to a control intervention. Other high-ranked and clinically effective interventions (when compared to a control intervention) were muscle-energy technique plus exercise (MD = 4.37; 95% CI = -8.01 to -0.74), as well as soft tissue techniques plus exercise (MD = -3.01; 95% CI = -5.1 to -0.92) to reduce short-term headache intensity, and dry needling plus exercise (MD = -2.92; 95% CI = -4.73 to -1.11) to reduce short-term headache frequency. These results were based on a low certainty of evidence. CONCLUSION: The 4 most highly ranked interventions can be considered in clinical practice. However, no conclusive recommendation can be made due to the low certainty of evidence. IMPACT: Combined interventions such as spinal joint manipulation plus dry needling and muscle-energy technique or soft tissue techniques or dry needling plus exercises seem to be the best interventions to reduce short-term cervicogenic headache intensity and/or frequency.

Reliability and measurement properties of upper cervical flexion-extension range of motion testing in people with cervicogenic headache and asymptomatic controls.

OBJECTIVE: The objective was to determine reliability of sagittal plane range of motion (ROM) assessment in a healthy population and in people with cervicogenic headache (CGH). METHODS: Upper cervical flexion/extension ROM was measured using an iPhone magnetometer sensor and retraction/protraction ROM measured by linear displacement. Two independent raters evaluated these movements in 33 subjects with CGH and 33 age and gender matched asymptomatic healthy controls on two occasions. Measurement procedures were standardized; and the order of testing randomized. Reliability, standard error of measurement (SEM) and minimum detectable change (MDC) were calculated. RESULTS: Subjects comprised 30 females and 36 males. The iPhone method demonstrated high reliability (ICC >0.82) with SEM values ranging from 0.62 to 1.0 and MDC values ranging from 1.70 to 4.81 respectively. Evaluation of linear displacement demonstrated moderate reliability (ICC >64). with SEM values ranging from 0.38 to 1.91 and MDC values ranging from 1.05 to 1.63 respectively. Compared to healthy controls, upper cervical flexion, retraction and protraction ROM was significantly less in the CGH group with mean difference of 6.50°, 1.52 cm and 2.34 cm respectively. DISCUSSION: Upper cervical spine sagittal plane ROM can be measured with moderate to high reliability and was found to be more restricted in people with CGH.

Post-traumatic headache pathophysiology in paediatric concussion: A systematic review.

Post-traumatic headache (PTH) represents the most common acute and persistent symptom following concussion in children, yet the underlying pathophysiology remains unclear. This systematic review sought to: (i) rigorously examine the current evidence of PTH pathophysiology in paediatric concussion (0-18 years), (ii) assess the quality of evidence, and (iii) provide directions for future research in accordance with PRISMA guidelines. Eligible studies (n = 19) totalling 1214 concussion participants investigated cerebrovascular function (n = 6), white matter integrity (n = 3), functional connectivity (n = 3), electrophysiology (n = 1), neurometabolics (n = 2), biological fluid markers (n = 4), vestibular and oculomotor function (n = 4); two studies used a multi-modal approach. Majority of studies were rated as fair quality (90%) and Level 3 evidence (84%). The true underlying mechanisms of PTH following paediatric concussion remain unclear. Overall quality of the available evidence is generally weak with a fair risk of bias and characterised by relative scarcity and lack of specificity of PTH pathophysiology. Future research is required to rigorously isolate pathophysiology specific to PTH with strict adherence to clinical definitions and standardised measurement tools of PTH.

Hypersensitivity to PACAP-38 in post-traumatic headache: a randomized clinical trial.

Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38), known for its role in migraine pathogenesis, has been identified as a novel drug target. Given the clinical parallels between post-traumatic headache (PTH) and migraine, we explored the possible role of PACAP-38 in the pathogenesis of PTH. To this end, we conducted a randomized, double-blind, placebo-controlled, two-way crossover trial involving adult participants diagnosed with persistent PTH resulting from mild traumatic brain injury. Participants were randomly assigned to receive a 20-min continuous intravenous infusion of either PACAP-38 (10 pmol/kg/min) or placebo (isotonic saline) on two separate experimental days, with a 1-week washout period in between. The primary outcome was the difference in incidence of migraine-like headache between PACAP-38 and placebo during a 12-h observational period post-infusion. The secondary outcome was the difference in the area under the curve (AUC) for baseline-corrected median headache intensity scores during the same 12-h observational period. Of 49 individuals assessed for eligibility, 21 were enrolled and completed the trial. The participants had a mean age of 35.2 years, and 16 (76%) were female. Most [19 of 21 (90%)] had a migraine-like phenotype. During the 12-h observational period, 20 of 21 (95%) participants developed migraine-like headache after intravenous infusion of PACAP-38, compared with two (10%) participants after placebo (P < 0.001). Furthermore, the baseline-corrected AUC values for median headache intensity scores during the 12-h observational period was higher after PACAP-38 than placebo (P < 0.001). These compelling results demonstrate that PACAP-38 is potent inducer of migraine-like headache in people with persistent PTH. Thus, targeting PACAP-38 signalling might be a promising avenue for the treatment of PTH.

Athrodesis of the lateral atlanto-axial joint for the relief of neck pain and cervicogenic headache.

BACKGROUND: Osteoarthrosis of the lateral atlanto-axial joint (LAAJ) may be a cause of upper neck pain and headache. Intra-articular injection of steroids may provide only short-lasting relief. For intractable pain, arthrodesis of the joint might be considered. OBJECTIVE: To determine the success rates of arthrodesis of the lateral atlanto-axial joint for relieving neck pain and disability. DESIGN: Practice audit. SETTING: Private practice of senior author. SUBJECTS: Prospective series of 23 consecutive patients. METHODS: Outcomes were measured using a numerical rating scale for neck pain, and the Neck Disability Index for disability. Success rates were calculated for various degrees of improvement of neck pain at long-term follow-up (8-40 months), and for achieving various combinations of improvement of both neck pain and disability. RESULTS: Complete relief of pain was achieved in 40% of patients, with a further 40% achieving at least 50% relief. At long-term follow-up, 30% of patients had no neck pain and no disability, and a further 25% had only minimal pain, minimal disability, or both. CONCLUSIONS: The present study did not corroborate earlier studies that claimed outstanding outcomes for arthrodesis of the LAAJ, but its outcomes are consonant with more recent studies that provided transparent outcome data. These studies provide Pain Physicians with empirical data on success rates and outcomes, upon which they can base their consideration of referral for arthrodesis.

Treatment Options for Posttraumatic Headache: A Current Review of the Literature.

PURPOSE OF REVIEW: We evaluate evidence-based treatments for posttraumatic headache (PTH), a secondary headache disorder resulting from traumatic brain injury (TBI), comprising nearly 4% of all symptomatic headache disorders. Utilizing recent publications, we aim to inform clinicians of current treatment methods. RECENT FINDINGS: There is limited research on PTH treatment. A randomized controlled trial (RCT) of metoclopramide with diphenhydramine for acute PTH found that the treatment group (N = 81) experienced more significant pain improvement than placebo by 1.4 points. For persistent PTH, an open-label study of erenumab (N = 89) found that 28% of participants reported ≥ 50% reduction in moderate-to-severe headache days, but an RCT of fremanezumab showed a non-significant reduction in moderate-to-severe headache days. A randomized crossover study of 40 patients with persistent PTH found that onabotulinum toxin-A decreased cumulative number of headaches/week by 43.3% in the treatment group and increased by 35.1% among placebos. In a study of military veterans with severe posttraumatic stress disorder and persistent/delayed onset PTH (N = 193), patients who received Cognitive Behavioral Therapy reported significant improvements in headache-related disability compared to usual care (aggregate mean HIT-6, -3.4). A transcranial magnetic stimulation (N = 24) study found that 58% of participants with mild TBI-related headache experienced a 50% reduction in headache frequency. New studies indicate promise in improving clinically important outcomes of PTH. However, more research is necessary to determine the optimal treatment and whether combining pharmacologic and nonpharmacologic treatment versus a single modality is more effective.

Is device guided training targeted to the craniocervical flexor and extensor muscles efficacious? A preliminary randomized controlled trial in a cervicogenic headache population.

BACKGROUND: Specific neck exercise is effective in the management of cervicogenic headache (CH). The Spinertial device was designed to facilitate craniocervical flexion and extension training, but its efficacy, judged on change in headache impact, has not been tested. OBJECTIVE: To compare guided and progressive resisted specific neck exercise targeted to the craniocervical flexors and extensors (SNE-fe) performed with Spinertial device to progressive SNE-fe without the device in a cohort with CH. DESIGN: Randomised controlled trial. METHODS: Twenty-eight participants with CH were randomly allocated to the Spinertial group (SG) or SNE-fe exercise group without the device (EG). Both groups performed 12 sessions of SNE-fe over six-weeks. The primary outcome was headache impact (HIT-6). Secondary outcomes were the craniocervical flexion test (CCFT), upper cervical (UCS) and lower cervical range of movement, flexion rotation test (FRT) analysed as more or less restricted side (MRS, LRS), the self-reported global rating of change (GROC-scale) and satisfaction with the exercise program (PACES). Outcomes were measured at baseline, post-intervention (T1) and after 1-month (T2). RESULTS: Significant between-groups differences were found favouring the SG for HIT-6 (T1 p = 0.010, d = 0.5; T2 p < 0.004, d = 0.4), CCFT, UCS ROM, FRT MRS, FRT LRS, PACES and GROC-scale (T1: all p < 0.01; T2: all p < 0.01). Effects sizes were large (>0.8) at T1 and T2. No between-groups differences were found for lower cervical ROM. CONCLUSION: Training with the Spinertial was more effective than SNE without the device for improving the impact of headache, the endurance of deep neck flexors and UCS ROM in participants with CH.