Indomethacin-Responsive Headache Disorders.

OBJECTIVE: This article describes the clinical features and treatment of the indomethacin-responsive headache disorders paroxysmal hemicrania and hemicrania continua. LATEST DEVELOPMENTS: Both paroxysmal hemicrania and hemicrania continua are treated with indomethacin at the lowest clinically useful dose. It has recently become clear that some patients with either condition may respond to treatment with noninvasive vagus nerve stimulation, which can be both indomethacin sparing and, in some cases, headache controlling. Given the lifelong nature of both paroxysmal hemicrania and hemicrania continua, brain imaging with MRI is recommended when the conditions are identified, specifically including pituitary views. ESSENTIAL POINTS: Paroxysmal hemicrania and hemicrania continua are indomethacin-responsive headache disorders that offer a rewarding and unique opportunity to provide marked clinical improvement when recognized and treated appropriately. These disorders share the final common pathway of the trigeminal-autonomic reflex, with head pain and cranial autonomic features, and are differentiated pathophysiologically by the pattern of brain involvement, which can be seen using functional imaging. They have distinct differential diagnoses to which the clinician needs to remain alert.

Adapting psychedelic medicine for headache and chronic pain disorders.

INTRODUCTION: While the majority of current research and development surrounds depression, demoralization, and substance use disorders, there are numerous reports of psychedelics having beneficial effects in other branches of medicine, including for headache disorders and chronic pain. AREAS COVERED: This perspective reviews conventional forms of treatment for headache and other chronic pain disorders and describes historical, recent, and ongoing investigations of the therapeutic effects of psychedelics in these disorders. The first two clinical trials of psilocybin in headache disorders and recent case reports of psilocybin mushroom self-administration in chronic pain patients are described. This perspective highlights several factors related to the application of psychedelics in chronic pain disorders, comparing this with the standard psychedelic-assisted psychotherapy model of treatment. EXPERT OPINION: When faced with a more constricted view of psychedelic medicine that features larger doses, underscores subjective effects in the mediation of therapeutic outcomes, and requires adjunctive psychotherapy to ensure safety and efficacy, the application of psychedelics in headache and chronic pain disorders may face challenges. It will be important to allow for flexibility and adaptation in protocols to evaluate different treatment paradigms, mechanisms of action, and the range of pharmacologic and extra-pharmacologic factors that affect psychedelic treatment outcomes.

Trial protocol for a multicenter randomized controlled trial to assess the efficacy and safety of intravenous ketamine for chronic daily headaches: the "KetHead" trial.

BACKGROUND: Chronic daily headaches (CDH) are common and associated with significant morbidity, poor quality of life, and substantial burden on the healthcare system. CDH tends to be refractory to conventional medical management and/or patients cannot afford expensive treatments. It is stipulated that CDH share a mechanism of central sensitization in the trigeminocervical complex, mediated by activation of the N-methyl-D-aspartate (NMDA) receptors. Ketamine, a non-competitive NMDA antagonist, has been used in the treatment of chronic pain, but its role in CDH has not been completely established. This trial aims to evaluate the effect of high-dose IV ketamine infusions (compared to placebo) on the number of headache days at 28 days post-infusion. METHODS: A multicenter, placebo-controlled, randomized controlled trial will be conducted with two parallel groups and blinding of participants and outcome assessors. The study will include 56 adults with a CDH diagnosis as per ICHD-3 criteria. Participants will be randomized (1:1) to either ketamine (1 mg. kg-1 bolus followed by infusion of 1 mg. kg-1. h-1 for 6 h) or placebo (0.9% saline in the same volume and infusion rate as the trial medication) bolus and infusion for 6 h. The impact on the number of monthly headache days, headache intensity, physical activity, mood, sleep, quality of life, analgesic consumption, and adverse effects will be recorded at baseline, immediately post-infusion, and from 1 to 28 days, 29 to 56 days, and 57 to 84 days after the infusion DISCUSSION: Despite advancements in treatment, many patients continue to suffer from CDH. This trial investigates whether high-dose IV ketamine infusions can effectively and safely improve the CDH burden as compared to a placebo infusion. This treatment could become a safe, affordable, and widely available option for patients living with refractory headache. TRIAL REGISTRATION: ClinicalTrials.gov NCT05306899. Registered on April 1, 2022.

The effectiveness of botulinum toxin for chronic tension-type headache prophylaxis: A systematic review and meta-analysis.

BACKGROUND: A systematic and meta-analysis was conducted to examine the evidence of the effects of botulinum toxin A on chronic tension-type headache. METHODS: Cochrane, Embase, Ovid, ProQuest, PubMed, Scopus, Web-of-Science databases, and ClinicallTrials.gov registry were systematically searched for studies examining the effects of botulinum toxin A on tension-type headaches. The records were screened by two independent reviewers using pre-determined eligibility criteria. DerSimonian Liard random-effects meta-analyses were performed using the 'meta' package (5.2-0) in R (4.2.0). Risk of bias and quality of evidence were assessed using the Cochrane Collaboration's Tool RoB 2 and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Clinical significance was determined using pre-defined minimal clinically important differences. RESULTS: Eleven controlled trials were included (390 botulinum toxin A, 297 controls). Botulinum toxin A was associated with significant improvements in standardized headache intensity (-0.502 standard deviations [-0.945, -0.058]), headache frequency (-2.830 days/month [-4.082, -1.578]), daily headache duration (-0.965 [-1.860, -0.069]) and the frequency of acute pain medication use (-2.200 days/month [-3.485, -0.915]) vs controls. Botulinum toxin A-associated improvements exceeded minimal clinically important differences for headache intensity, frequency, and acute pain medication use. A 79% (28%, 150%) greater response rate was observed for botulinum toxin A vs controls in improving chronic tension-type headache. Treatment of eight chronic tension-type headache patients was sufficient to elicit a therapeutic response in one patient. CONCLUSIONS: Corroborating the current mechanistic evidence, our meta-analysis supports the utility of botulinum toxin A for managing chronic tension-type headaches. However, due to limitations in the quality of evidence, adequately-powered high-quality controlled trials examining the effects of Botulinum toxin A on chronic tension-type headache are warranted. REGISTRATION: Protocol preregistered in PROSPERO International Prospective Register of Systematic Reviews (CRD42020178616).

UK medical cannabis registry: assessment of clinical outcomes in patients with headache disorders.

OBJECTIVES: Headache disorders are a common cause of disability and reduced health-related quality of life globally. Growing evidence supports the use of cannabis-based medicinal products (CBMPs) for chronic pain; however, a paucity of research specifically focuses on CBMPs' efficacy and safety in headache disorders. This study aims to assess changes in validated patient-reported outcome measures (PROMs) in patients with headaches prescribed CBMPs and investigate the clinical safety in this population. METHODS: A case series of the UK Medical Cannabis Registry was conducted. Primary outcomes were changes from baseline in PROMs (Headache Impact Test-6 (HIT-6), Migraine Disability Assessment (MIDAS), EQ-5D-5L, Generalized Anxiety Disorder-7 (GAD-7) questionnaire and Single-Item Sleep Quality Scale (SQS)) at 1-, 3-, and 6-months follow-up. P-values <0.050 were deemed statistically significant. RESULTS: Ninety-seven patients were identified for inclusion. Improvements in HIT-6, MIDAS, EQ-5D-5L and SQS were observed at 1-, 3-, and 6-months (p < 0.005) follow-up. GAD-7 improved at 1- and 3-months (p < 0.050). Seventeen (17.5%) patients experienced a total of 113 (116.5%) adverse events. CONCLUSION: Improvements in headache/migraine-specific PROMs and general health-related quality of life were associated with the initiation of CBMPs in patients with headache disorders. Cautious interpretation of results is necessary, and randomized control trials are required to ascertain causality.

Impact of preventive pill-based treatment on migraine days: A secondary outcome study of the Childhood and Adolescent Migraine Prevention (CHAMP) trial and a comparison of self-report to nosology-derived assessments.

OBJECTIVE: To examine group differences in self-reported migraine days among youth who completed the Childhood and Adolescent Migraine Prevention (CHAMP) trial prior to its closure and explore the relationship between self-reported and "nosology-derived" (i.e., International Classification of Headache Disorders, 3rd edition [ICHD-3]) migraine days. BACKGROUND: The CHAMP trial compared amitriptyline and topiramate to placebo for migraine prevention in youth and proposed to analyze change in migraine days as a secondary outcome. There is considerable variability in the field regarding what constitutes a "migraine day," how this is determined and reported in trials, and how consistent these measures are with diagnostic nosology. METHODS: CHAMP trial completers (N = 175) were randomized to receive amitriptyline (n = 77), topiramate (n = 63), or placebo (n = 35). Participants maintained daily headache diaries where they reported each day with headache and if they considered that headache to be a migraine. For each headache day, participants completed a symptom record and reported about symptoms such as pain location(s) and presence of nausea/vomiting or photophobia and phonophobia. We examined group differences in self-reported migraine days at trial completion (summed from trial weeks 20-24) compared to baseline. We also used an algorithm to determine whether participants' symptom reports met ICHD-3 criteria for migraine without aura, and examined the association between self-reported and "nosology-derived" migraine days. RESULTS: Results showed no significant differences between groups in self-reported migraine days over the course of the trial. Self-reported and "nosology-derived" migraine days during the baseline and treatment phases were strongly associated (r's = 0.73 and 0.83, respectively; p's < 0.001). CONCLUSION: Regardless of treatment, CHAMP trial completers showed clinically important reductions in self-reported migraine days over the course of the trial (about 3.8 days less). The strong association between self-reported and "nosology-derived" migraine days suggests youth with migraine can recognize a day with migraine and reliably report their headache features and symptoms. Greater rigor and transparency in the calculation and reporting of migraine days in trials is needed.

Narrative review of peripheral nerve blocks for the management of headache.

OBJECTIVE: To provide an overview of the current available literature on peripheral nerve blocks for the management of migraine and other headache disorders in adults. BACKGROUND: Peripheral nerve blocks have been commonly performed in the headache practice for migraine, cluster headache, occipital neuralgia, and other headache disorders, despite a paucity of evidence supporting their use historically. In the past decade, there has been an effort to explore the efficacy and safety of peripheral nerve blocks for the management of headache, with the greatest interest centered around greater occipital blocks. DESIGN: We performed a search in PubMed using key words including "occipital nerve blocks," "peripheral nerve blocks," "occipital nerve," "migraine," "cluster headache," and "neuralgia." We reviewed the randomized controlled trials (RCTs), observational studies, and case series, and summarized the anatomy, techniques, and the evidence for the use of peripheral nerve blocks in different headache disorders, with particular focus on available RCTs. Case reports were included for a detail review of adverse events. RESULTS: Of 12 RCTs examining the use of greater occipital nerve blocks for migraine, all but one demonstrate efficacy with reduction in headache frequency, intensity, and/or duration compared to placebo. Studies have not demonstrated a difference in clinical outcomes with the use of corticosteroids for nerve blocks compared to blocks with local anesthetic in the treatment of migraine. There are two RCTs supporting the use of greater occipital blockade for cluster headache, both showing benefit of suboccipitally injected corticosteroid. One RCT suggests benefit of greater occipital nerve blocks for cervicogenic headache. Observational studies and case series/reports show that greater occipital nerve block may be effective in prolonged migraine aura, status migrainosus, post-dural puncture headache, and occipital neuralgia. Overall, peripheral nerve blocks are well tolerated. Serious side effects are rare but have been reported, including acute cerebellar syndrome and infection. CONCLUSIONS: Peripheral nerve blocks, especially occipital nerve blocks, are a viable treatment option for migraine and may be helpful in cluster headache as a transitional therapy or rescue therapy. Additional prospective studies are needed to investigate the efficacy and safety of occipital nerve blocks for long-term migraine prevention, as well as for other headache disorders, such as occipital neuralgia.

Paroxysmal hemicrania in children and adolescents: A systematic review.

OBJECTIVE: We aimed to report the accessible demographic, clinical, and radiological characteristics of reported pediatric paroxysmal hemicrania (PH). INTRODUCTION: It has been a while since PH in a child was first described. However, it is still unknown whether children's PH follows the same patterns as adults. METHODS: This study followed the latest version of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). PubMed, Web of Science, and Scopus were searched systematically without time limitation. We included all English-language, peer-reviewed articles, including observational or interventional studies reporting PH cases in children or adolescents based on the International Classification of Headache Disorders (ICHD) criteria. Data extracted included PH class; sex; age; age of onset; frequency, duration, site, severity, and quality of pains; triggers; and autonomic and migrainous symptoms, as well as a sense of restlessness/agitation, response to treatment, laboratory investigations, imaging, comorbidity, and family history. For quality assessment, two independent reviewers (MB and VM) assessed the methodological quality of the included studies through the Joanna Briggs Institute's critical appraisal checklist. RESULTS: A total of 182 records were identified and reduced to 116 after removing duplicates. After screening, 22 articles met the inclusion criteria. Overall, the studies represented 35 children or adolescents with PH. We found a boy-to-girl ratio of 1.125:1. Onset occurred at a broad range of 1 to 14 years old. The mean age of onset among reported cases in children and adolescents was 6.5 years, while the mean age of diagnosis was 8.2 years. [Correction added on 22 August 2022, after first online publication: In the preceding sentence, 6.3 and 7.9 years were changed to 6.5 and 8.2 years, respectively.] The attacks' frequency and duration were greatly varied. Left-sided pain occurred twice as often as right-sided pain. The characteristics of the pain were usually severe in intensity. In nearly all of the cases, it was accompanied by ipsilateral cranial autonomic features. While most attacks were spontaneous, there were some common triggers. The physical examination, electroencephalogram, and brain magnetic resonance imaging had normal findings. Almost all patients benefited from indomethacin and showed complete responses to treatment, while some needed combination treatment of indomethacin with other medications. CONCLUSION: Although pediatric-onset PH has similar features to adult-onset PH, there are some challenges with ICHD criteria for younger children that limit the ability to confidently assign a diagnosis. Moreover, owing to concomitant migrainous features, PH may be confused with migraine in children and adolescents.

Etoricoxib and celecoxib sensitive indomethacin-responsive headache disorders.

Indomethacin-responsive headaches encompass a group of disorders which include a subset of the trigeminal autonomic cephalalgias and other paroxysmal, often precipitated primary headaches. Many patients show a rapid therapeutic response to indomethacin, which is limited by intolerability. Etoricoxib and celecoxib, selective inhibitors of cyclo-oxygenase-2 (COX-2), spare gastroduodenal COX-1 activity and are less likely to cause gastrointestinal adverse effects than indomethacin. We report a case series of eight patients, seven who responded to etoricoxib and one patient who responded to celecoxib.

Natural History of Abortive Medication Withdrawal in the Management of Pediatric Medication Overuse Headache.

OBJECTIVE: The objective of this study is to document pain scores during withdrawal of abortive medication in patients diagnosed with medication overuse headache. DESIGN: Cross-sectional study. SETTING: Children's National Hospital's Headache Program. SUBJECTS: Patients 6-18 years of age who presented to the Headache Clinic at Children's National Hospital with presumed medication overuse headache between March 2017 and March 2019 were invited to participate. METHODS: Patients were instructed to abruptly discontinue overused medications and record their headache characteristics daily in a diary for 8 weeks. RESULTS: Fourteen diaries were returned and analyzed at a 4-week follow-up visit. Ninety-three percent of the patients were females, with a median age of 14.9 years (standard deviation [SD] = 2.0). The average headache intensity upon study entry was 4.7 out of 10 (SD = 2.5), and the average headache intensity upon study completion was 3.1 (SD = 2.5). Of the patients, 57% had daily headaches upon study entry, 71% had improved pain intensity from the first diary entry to the last diary entry, and 57% had complete headache resolution at an average of 7.6 days from medication discontinuation (SD = 5.1). Ibuprofen was the most overused medication (71%). CONCLUSIONS: Our findings suggest that medication overuse headache will improve in the majority of pediatric patients who abruptly stop the offending medication(s) in an average of 8 days from withdrawal. Average pain intensity was reduced by more than one point among all patients who stopped taking abortive medications. Further larger-scale studies on medication withdrawal in pediatric patients with medication overuse headache could help us better understand whether this management strategy is effective.

OnabotulinumtoxinA for the treatment of headache: an updated review.

Botulinum toxin (BT) is a neurotoxin produced by Clostridium botulinum, a gram-positive anaerobic bacterium. Systemic human intoxication from BT following oral ingestion results in acute and life-threatening muscle paralysis called botulism. BT has a wide scope of therapeutic uses, including conditions associated with increased muscle tone, smooth muscle hyperactivity, salivation, sweating, and allergies, as well as for cosmetic purposes. Several commercial forms of BT are available for medical use, including Botox (onabotulinumtoxinA). Multiple studies have found evidence of an analgesic effect of onabotulinumtoxinA and demonstrated the benefits of its use for the treatment of various chronic pain disorders. In this review, we provide an update on the use of onabotulinumtoxinA for the treatment of headache disorders.

Efficacy and Safety of Repetitive Intravenous Sodium Valproate in Pediatric Patients With Refractory Chronic Headache Disorders: A Retrospective Review.

BACKGROUND: Chronic headache disorders can cause substantial disability and be treatment refractory. Often, these patients are excluded from clinical trials with leaving little evidence to guide treatment. In adults, divalproex sodium is an effective preventive migraine treatment. METHODS: All pediatric patients admitted for first-time sodium valproate infusions to treat refractory, chronic migraine (CM), new daily persistent headache, or persistent headache attributed to head trauma from January 2017 to October 2020 were identified for review. Each patient underwent a standardized, 4-day protocol. A new preventive was started one week after discharge. Data on headache frequency, severity, and acute medication use were collected through preadmission and postadmission clinic notes. Safety and tolerability were evaluated. Results were evaluated using descriptive statistics and compared with paired t-tests. RESULTS: Forty-five patients were identified for review. Patients with CM had a median of 7 previous preventive trials, and 85% had previously received alternative intravenous treatment for headache. Baseline headache pain significant decreased from 6.9/10 to 5.4/10 by 7-week postadmission follow up, (95% confidence interval = -0.7 to -2.4), P < 0.001. Use of medications for acute headache treatment decreased significantly from 2.1 days/week to 1.5 days/week, (95% confidence interval = -0.3 to -1), P < 0.001. Baseline headache frequency did not significantly change. At postadmission follow-up, 26 of 39 (67%) patients saw improvements in headache frequency, headache intensity, and/or acute pain medication usage. There were no serious adverse events. CONCLUSIONS: Repetitive sodium valproate infusions were well tolerated and significantly reduced baseline headache intensity and acute medication usage in pediatric patients with refractory, chronic headache disorders.

Development and Evaluation of an Integrated Outpatient Infusion Care Model for the Treatment of Pediatric Headache.

BACKGROUND: Care for pediatric patients with headache often occurs in high-cost settings such as emergency departments (EDs) and inpatient settings. Outpatient infusion centers have the potential to reduce care costs for pediatric headache management. METHODS: In this quality improvement study, we describe our experience in creating the capacity to support an integrated outpatient pediatric headache infusion care model through an infusion center. We compare costs of receiving headache treatment in this model with those in the emergency and inpatient settings. Because dihydroergotamine (DHE) is a costly infusion, encounters at which DHE was administered were analyzed separately. We track the number of ED visits and inpatient admissions for headache using run charts. As a balancing measure, we compare treatment efficacy between the infusion care model and the inpatient setting. RESULTS: The mean percentage increase in cost of receiving headache treatment in the inpatient setting with DHE was 61% (confidence interval [CI]: 30-99%), and that without DHE was 582% (CI: 299-1068%) compared with receiving equivalent treatments in the infusion center. The mean percentage increase in cost of receiving headache treatment in the ED was 30% (CI: -15 to 100%) compared with equivalent treatment in the infusion center. After the intervention, ED visits and inpatient admissions for headache decreased. The mean change in head pain was similar across care settings. CONCLUSIONS: Our findings demonstrate that developing an integrated ambulatory care model with infusion capacity for refractory pediatric headache is feasible, and our early outcomes suggest this may have a favorable impact on the overall value of care for this population.

Trajectory of treatment response in the child and adolescent migraine prevention (CHAMP) study: A randomized clinical trial.

OBJECTIVE: Identify preventive medication treatment response trajectories among youth participating in the Childhood and Adolescent Migraine Prevention study. METHODS: Data were evaluated from 328 youth (ages 8-17). Childhood and Adolescent Migraine Prevention study participants completed headache diaries during a 28-day baseline period and a 168-day active treatment period during which youth took amitriptyline, topiramate, or placebo. Daily headache occurrence trajectories were established across baseline and active treatment periods using longitudinal hierarchical linear modeling. We tested potential treatment group differences. We also compared final models to trajectory findings from a clinical trial of cognitive behavioral therapy plus amitriptyline for youth with chronic migraine to test for reproducibility. RESULTS: Daily headache occurrence showed stability across baseline. Active treatment models revealed decreases in headache frequency that were most notable early in the trial period. Baseline and active treatment models did not differ by treatment group and replicated trajectory cognitive behavioral therapy plus amitriptyline trial findings. CONCLUSIONS: Replicating headache frequency trajectories across clinical trials provides strong evidence that youth can improve quickly. Given no effect for medication, we need to better understand what drives this clinically meaningful improvement. Results also suggest an expected trajectory of treatment response for use in designing and determining endpoints for future clinical trials.Trial Registration. ClinicalTrials.gov Identifier: NCT01581281.

The Headache in Emergency Departments study: Opioid prescribing in patients presenting with headache. A multicenter, cross-sectional, observational study.

OBJECTIVE: To describe the patterns of opioid use in patients presenting to the emergency department (ED) with nontraumatic headache by severity and geography. BACKGROUND: International guidelines recognize opioids are ineffective in treating primary headache disorders. Globally, many countries are experiencing an opioid crisis. The ED can be a point of initial exposure leading to tolerance for patients. More geographically diverse data are required to inform practice. METHODS: This was a planned, multicenter, cross-sectional, observational substudy of the international Headache in Emergency Departments (HEAD) study. Participants were prospectively identified throughout March 2019 from 67 hospitals in Europe, Asia, Australia, and New Zealand. Adult patients with nontraumatic headache were included as identified by the local site investigator. RESULTS: Overall, 4536 patients were enrolled in the HEAD study. Opioids were administered in 1072/4536 (23.6%) patients in the ED, and 386/3792 (10.2%) of discharged patients. High opioid use occurred prehospital in Australia (190/1777, 10.7%) and New Zealand (55/593, 9.3%). Opioid use in the ED was highest in these countries (Australia: 586/1777, 33.0%; New Zealand: 221/593, 37.3%). Opioid prescription on discharge was highest in Singapore (125/442, 28.3%) and Hong Kong (12/49, 24.5%). Independent predictors of ED opioid administration included the following: severe headache (OR 4.2, 95% CI 3.1-5.5), pre-ED opioid use (OR 1.42, 95% CI 1.11-1.82), and long-term opioid use (OR 1.80, 95% CI 1.26-2.58). ED opioid administration independently predicted opioid prescription at discharge (OR 8.4, 95% CI 6.3-11.0). CONCLUSION: Opioid prescription for nontraumatic headache in the ED and on discharge varies internationally. Severe headache, prehospital opioid use, and long-term opioid use predicted ED opioid administration. ED opioid administration was a strong predictor of opioid prescription at discharge. These findings support education around policy and guidelines to ensure adherence to evidence-based interventions for headache.

Headache infusion centers: A survey on treatments provided, infusion center operations, and barriers to developing new infusion centers.

BACKGROUND: Infusion therapy refers to the intravenous administration of medicines and fluids for the treatment of status migrainosus, severe persistent headaches, or chronic headache. Headache practices and centers offer this treatment for patients as an alternative to the emergency department (ED) setting. However, little information is available in the literature on understanding the operations of an infusion center. OBJECTIVE: We sought to survey the Inpatient Headache & Emergency Medicine specialty section and the Academic Program Directors listserv of the American Headache Society (AHS) to better understand current practices. METHODS: A survey was advertised and distributed to the listservs of both the Inpatient Headache & Emergency Medicine specialty section and the Academic Program Directors, which combined included both academic and private practices. In addition, the survey was available on laptops at related events at an annual AHS meeting in Scottsdale. RESULTS: Of the 127 members of the combined group of both listservs, 50 responded with an overall survey response rate of 39%. Ten out of fifty were from programs with more than one responder completing the survey, leaving 40 unique headache programs. Academic programs made up the majority of programs (85%, 34/40). The total of 40 participating programs is comparable with the 47 academic headache programs listed on the American Migraine Foundation website at the time of the survey. Of the academic programs surveyed, most were hospital based (n = 23) compared with a satellite location (n = 11). Of all programs surveyed, 68% (27/40) offered infusion therapy. Of those that did not have an infusion practice (n = 13), the most common reason cited was insufficient staffing (n = 8). Key highlights of the survey included the following: The majority of programs offering infusions obtain prior authorization before scheduling (70%, 19/27) and offer patient availability 5 days/week (78%, 21/27) typically only during business hours (81%, 22/27). Programs reported that they typically give three to four medications during each infusion session (72%, 18/25). Treatment paradigms varied between programs. Programs surveyed were concentrated in the Northeast and Midwest regions of the United States. CONCLUSION: The limited number of headache infusion centers overall may contribute to the limited ability of headache infusion centers to prevent ED migraine visits. Headache patients can have unpredictable headache onset, and most of the infusion practices surveyed appeared to adapt to this by offering infusions most days during a work week. However, this need for multiple days per week may also explain the most common reason for not having an infusion practice, which is insufficient staffing. Various treatment paradigms are implemented by different practitioners, and future studies will have to focus on investigation of best practice.

Intra-arterial injection of lidocaine into middle meningeal artery to treat intractable headaches and severe migraine.

BACKGROUND AND PURPOSE: We report the results of intra-arterial injection of lidocaine in the middle meningeal artery in patients with intractable headache or status migrainosus. METHODS: We treated four patients with intra-arterial lidocaine (2 mg/ml) in doses up to 50 mg in each middle meningeal artery via a microcatheter bilaterally (except in one patient). In two patients with intractable headache, the daily maximum intensity of headache (graded by 11-point numeric rating scale) was recorded for 7 days postprocedure. In two patients with status migrainosus, migraine-related disability 3 months prior and after treatment using MIDAS (Migraine Disability Assessment) questionnaire was recorded. RESULTS: Intra-arterial lidocaine reduced the headache intensity from 8/10 and 10/10 to 0/10 in the two patients with intractable headaches for 2 days (day 0 and day 1) postprocedure. Despite recurrence of headache on day 2, the intensity was less than preprocedure intensity up to the last day recorded (by 3 and 2 points on day 7). In the two patients with status migrainosus, there was immediate reduction in headache intensity following intra-arterial lidocaine. The post treatment 3-month MIDAS score was lower in both patients compared with pretreatment 3-month score; 3 versus 30 and 55 versus 90. Severe disability preprocedure by MIDAS was reduced to little or no disability postprocedure in one patient. CONCLUSIONS: Intra-arterial lidocaine resulted in amelioration of headache in patients with intractable headache and those with status migrainosus with improvement lasting longer than the short half-life of lidocaine possibly related to central desensitization.

New daily persistent headache after SARS-CoV-2 infection: a report of two cases.

BACKGROUND: The 2019 Coronavirus (SARS-CoV-2) is a novel respiratory virus which causes Coronavirus Disease19 (COVID-19). Although the predominant clinical picture of COVID-19 is represented by respiratory symptoms, neurological manifestations are being increasingly recognized. Headache, in particular migraine-like and tension types, has been largely reported in patients suffering from COVID-19 both in the acute and the healing phase of the infection. New daily persistent headache (NDPH) is a primary headache characterized by persistent and daily painful symptoms, with pain becoming continuous and non-remitting within 24 h, and lasting more than 3 months. Even though an increasing number of reports describe patients who develop a persistent headache, diagnosis of NPDH has been rarely explored in the context of COVID-19. METHODS: Two patients with persistent headache and Sars-CoV-2 infection were identified. Both underwent a full clinical and neuroradiological evaluation. Blood sample with inflammatory biomarkers search was also performed. RESULTS: According to International Classifications of Headache Disorders diagnosis of probable new daily persistent headache was made. The treatment with high doses of steroids was associated with relief of symptoms. CONCLUSIONS: Our report described two cases of probable NDPH due to SARS-CoV-2 infection. Clinical evaluation of COVID-19 patients presenting with persistent headache should take into consideration NDPH. Given the supposed major role for neuroinflammation in the genesis of Sars-CoV-2-driven NDPH, immunomodulatory therapy should be promptly started. In line with this hypothesis, we obtained a good therapeutic response to short-term high dose of corticosteroids.

Dihydroergotamine infusion for pediatric refractory headache: A retrospective chart review.

BACKGROUND: Headaches are a common symptom in children. Children with refractory headaches may be admitted for inpatient treatment with intravenous dihydroergotamine mesylate (DHE). However, very few studies have characterized these patients and their treatment outcomes using validated, self-reported, pain scales. OBJECTIVE: The objective of this study was to describe demographic and clinical characteristics of children admitted for DHE infusion, determine DHE treatment outcomes by means of numeric pain scale ratings, and explore associations between treatment outcomes and clinical characteristics. METHODS: Retrospective chart review was completed in patients ages 5-21 admitted for DHE infusion from January 2013 to July 2018 at a large, pediatric academic medical center and community-based satellite center. All primary headache types were included. RESULTS: A total of 200 unique admissions for DHE were available for analysis. Overall, patients were predominantly White (87.5%, 175/200) and female (80.0%, 160/200) with an average age of 15.4 years (SD 2.3). Common comorbidities included obesity (42.0%, 81/193), anxiety (41.0%, 82/200), and depression (20.0%, 40/200). The mean length of stay was 2.4 days (SD 1.10; range 1-8 days). Most headaches (65.0%, 130/200) met the International Classification of Headache Disorders, 3rd edition criteria for migraine, followed by new daily persistent headache (25.5%, 51/200). Mean DHE maximum dose was 5.3 (SD 2.17; range 0.5-14.5 mg) with most patients requiring 3.5-6.5 mg. DHE was typically terminated at six doses (range 1-15). The most frequently reported adverse event was nausea (5.5%, 11/200). There was no difference in pain severity at admission across headache types, with an average baseline pain score of 8.1 (SD 1.6). Posttreatment reduction in pain score was statistically significant (range: -3.2 to -4.9; each p < 0.001) across all headache types. Overall, 84.0% (168/200) of the patients had some improvement in pain. More than half of the patients (53.5%, 107/200) showed at least moderate improvement (≥50.0% reduction in pain score), and 18.0% (36/200) had full headache resolution. Limited patients (16.0%, 32/200) experienced no improvement in pain. CONCLUSIONS: Treatment with DHE resulted in at least some improvement for most patients regardless of headache type or number of doses. Clinical trials stratified by headache type and comorbid factors could help clarify treatment algorithms to optimize patient outcomes.

The efficacy of botulinum toxin A treatment for tension-type or cervicogenic headache: a systematic review and meta-analysis of randomized, placebo-controlled trials.

OBJECTIVES: The pathogeneses of chronic tension-type headache (CTTH) and cervicogenic headache (CEH) are not well established. Peripheral activation or sensitization of myofascial nociceptors is suggested as a potential mechanism and injections of botulinum toxin (BONTA) have thus been used in the treatment for both headache conditions. BONTA inhibits the release of acetylcholine at the neuromuscular junction and inhibits contraction of skeletal muscles. If the pain is precipitated by increased tone in cervical muscles, local injections of BONTA could represent a prophylactic measure. However, the treatment is still controversial, and a thorough assessment of the current evidence is required. This review aims to assess the evidence of BONTA injection as a prophylactic treatment for CTTH and CEH by reviewing and examining the quality of placebo-controlled, randomized trials. METHODS: Data sources: we searched in the following databases: PubMed (including Medline), Embase, Cochrane Central register of Controlled Trials, Cinahl, Amed, SCOPUS and Google Scholar including other repository sources. Both MeSH and free keywords were used in conducting the systematic search in the databases. The search covered publications from the root of the databases to November 2020. STUDY ELIGIBILITY CRITERIA: The review included RCTs, comparing single treatment of BONTA with placebo on patients with CTTH or CEH above 18 years of age, by measuring pain severity/relief or headache frequency. DATA EXTRACTION: The following data were extracted: year of publication, country, setting, trial design, number of participants, injection procedure, BONTA dosages, and clinical outcome measures. STUDY APPRAISAL: To assess validity and quality, and risk of bias, the Oxford Pain Validity Scale, Modified Jadad Scale, last version of Cochrane Collaboration's tool for assessing risk of bias (RoB 2), and the CONSORT 2010 Checklist were used. The trials were assessed, and quality scored independently by two of the reviewers. A quantitative synthesis and meta-analyses of headache frequency and intensity were performed. RESULTS: We extracted 16 trials, 12 on prophylactic BONTA treatment for CTTH and four on CEH. Of these 12 trials (8 on CTTH and 4 on CEH) were included in the quantitative synthesis. A majority of the trials found no significant difference on the primary outcome measure when BONTA treatment was compared with placebo. Three "positive" trials, reporting significant difference in favor of BONTA treatment, but two of these were hampered by low validity and quality scores and high risk of bias. CONCLUSIONS: There is no clear clinical evidence supporting prophylactic treatment with BONTA for CTTH or CEH.