Sequential administration of peripheral nerve blocks and onabotulinumtoxinA for the treatment of chronic migraine and other headache disorders-A retrospective tolerability and safety study.

OBJECTIVE: To determine the tolerability and safety of concurrent peripheral nerve blocks and onabotulinumtoxinA treatment during a single outpatient clinic procedure visit. BACKGROUND: Procedural interventions are available for the treatment of headache disorders. OnabotulinumtoxinA and peripheral nerve blocks are used as alternatives or in addition to oral therapies to reduce the frequency and intensity of migraine attacks. There is currently a lack of safety data focusing on the sequential administration of local anesthetic via peripheral nerve blocks and onabotulinumtoxinA during a single clinical encounter for the treatment of headache. The primary aim of the study was to determine the safety and tolerability of concurrent peripheral nerve blockade and onabotulinumtoxinA injections during a single outpatient clinic procedure visit. We hypothesized that the dual intervention would be safe and well tolerated by patients with chronic migraine and other headache disorders. METHODS: A retrospective chart review was performed using clinical data from patients seen by multiple providers over a 16-month timeframe at one outpatient headache clinic. Patients were identified by procedure codes and those receiving peripheral nerve block(s) and onabotulinumtoxinA injections during a single encounter within the study period were eligible for inclusion. Inclusion criteria were (1) patients 18 years and older who were (2) receiving both peripheral nerve blocks and onabotulinumtoxinA injections for the treatment of chronic migraine. Patients were excluded if they were under age 18, received their procedure outside of the clinic (emergency room, inpatient ward), or were receiving sphenopalatine ganglion blocks. Age- and sex-matched patients who received one procedure, either peripheral nerve blocks or onabotulinumtoxinA, were used for control. The primary outcome of this safety study was the number of adverse events that occurred in the dual intervention group compared to the single intervention control arms. Information regarding adverse events was gathered via retrospective chart review. If an adverse event was recorded, it was then graded by the reviewer utilizing the Common Terminology Criteria for Adverse Events ranging from Grade 1 Mild Event to Grade 5 Death. Additionally, it was noted whether the adverse event led to treatment discontinuation. RESULTS: In total, 375 patients were considered eligible for inclusion in the study. After age and sex matching of controls, 131 patients receiving dual intervention were able to be compared to 131 patients receiving onabotulinumtoxinA alone and 104 patients receiving dual intervention were able to be compared to 104 patients receiving peripheral nerve block(s) alone. The primary endpoint analysis showed no significant difference in total adverse events between dual intervention compared to nerve blocks alone or onabotulinumtoxinA alone. The number of adverse events that led to treatment discontinuation approached but did not reach statistical significance for those receiving dual intervention versus onabotulinumtoxinA alone in the number of adverse events that led to treatment termination (4.6%, 6/131 vs. 0.8%, 1/131, p = 0.065); however, the number of patients who discontinued therapy was not significantly different between those groups (2.3%, 3/131 vs. 0.8%, 1/131; p = 0.314; odds ratio 0.3 [0-3.2]; p = 0.338). CONCLUSIONS: In this retrospective chart review, there was no significant difference in adverse events or therapy discontinuation between patients receiving sequential peripheral nerve block(s) and onabotulinumtoxinA injections versus those receiving either peripheral nerve block(s) or onabotulinumtoxinA injections alone. As a result, we concluded that the combination procedure is likely safe and well tolerated in routine clinical practice.

A qualitative evidence synthesis of patient perspectives on migraine treatment features and outcomes.

OBJECTIVES: We aimed to identify migraine treatment features preferred by patients and treatment outcomes most valued by patients. BACKGROUND: The values and preferences of people living with migraine are critical for both the choice of acute therapy and management approach of migraine. METHODS: We conducted a qualitative evidence synthesis. Two reviewers independently selected studies, appraised methodological quality, and undertook a framework synthesis. We developed summary of findings tables following the approach of Grading of Recommendations, Assessment, Development and Evaluations Confidence in the Evidence from Reviews of Qualitative Research to assess confidence in the findings. RESULTS: Of 1691 candidate references, we included 19 studies (21 publications) involving 459 patients. The studies mostly recruited White women from North America (11 studies) and Europe (8 studies). We identified eight themes encompassing features preferred by patients in a migraine treatment process. Themes described a treatment process that included shared decision-making, a tailored approach, trust in health-care professionals, sharing of knowledge and diversity of treatment options, a holistic approach that does not just address the headache, ease of communication especially for complex treatments, a non-undermining approach, and reciprocity with mutual respect between patient and provider. In terms of the treatment itself, seven themes emerged including patients' preferences for nonpharmacologic treatment, high effectiveness, rapidity of action, long-lasting effect, lower cost and more accessibility, self-management/self-delivery option that increases autonomy, and a mixed preference for abortive versus prophylactic treatments. The treatment outcomes that have high value to patients included maintaining or improving function; avoiding side effects, potential for addiction to medications, and pain reoccurrence; and avoiding non-headache symptoms such as nausea, vomiting, and sensitivity to light or sounds. CONCLUSION: Patient values and preferences were individually constructed, varied widely, and could be at odds with conventional medical perspectives and evidence of treatment effects. Considering the availability of numerous treatments for acute migraine, it is necessary that decision-making incorporates patient values and preferences identified in qualitative research. The findings of this qualitative synthesis can be used to facilitate an individually tailored approach, strengthen the patient-health-care system relationship, and guide choices and decisions in the context of a clinical encounter or a clinical practice guideline.

A Review of Underserved and Vulnerable Populations in Headache Medicine in the United States: Challenges and Opportunities.

PURPOSE OF REVIEW: This review will briefly summarize recent literature published on headache disparities in underserved and vulnerable populations. It will also report the personal observations of headache medicine providers working with underserved and vulnerable populations in the USA, specifically in an urban practice dedicated to patients in a safety net program and a rural practice dedicated to Native American patients. RECENT FINDINGS: Headache disorders are recognized as one of the most prevalent neurological conditions. People with headache and migraine encounter several barriers to obtaining appropriate care, which are magnified in vulnerable and underserved populations. Research has shown disparities in headache and migraine diagnosis, prevalence rates, treatment, and outcomes based on race, socioeconomic status, and geography. Continued research regarding disparities in headache medicine is required. Strategies to address the identified challenges, including structural competence and the underrepresented in medicine pipeline, are reviewed.

Narrative review of neuroimaging in migraine with aura.

OBJECTIVE: To improve the understanding of the role and utility of various neuroimaging modalities (clinical and research) for the evaluation of migraine aura (MA) and hemiplegic migraine during the ictal and interictal phases. BACKGROUND: MA is defined by reversible neurologic symptoms and is considered a manifestation of a primary condition. As such, most patients with MA do not require imaging. However, if there are atypical features, change in symptom pattern, or it is a first-time presentation, neuroimaging may be used to evaluate for secondary conditions. Neuroimaging includes many modalities, and it is important to consider what information is being captured by these modalities (i.e., structural vs. functional). Imaging abnormalities may be noted both during (ictal) and between (interictal) MA attacks, and it is important for clinicians to be familiar with neuroimaging findings reported in migraine with aura (MWA) compared with other conditions. METHODS: With the assistance of a medical librarian, we performed a review of the literature pertaining to MWA and neuroimaging in PubMed. Search terms included were magnetic resonance imaging, positron-emission tomography, single photon-emission computed tomography, functional magnetic resonance imaging, and migraine with aura. We hand-searched these references to inform our subsequent literature review. RESULTS: Acute MA can be associated with several unique neuroimaging findings-reversible cortical diffusion restriction, cortical venous engorgement, and a "biphasic" transition from hypoperfusion to hyperperfusion. Imaging findings during MA tend to span more than one vascular territory. Between acute attacks, neuroimaging in people with MWA can resemble migraine without aura in terms of white matter abnormalities and "infarct-like lesions." Research imaging modalities such as volumetric analysis and functional imaging have demonstrated unique findings in migraine with aura. CONCLUSION: Although migraine is a clinical diagnosis, understanding of neuroimaging findings in MWA can help clinicians interpret imaging findings and improve patient care.

The intersection of COVID-19, school, and headaches: Problems and solutions.

OBJECTIVE: To equip clinicians with recommendations specific to concerns related to the novel coronavirus disease 2019 (COVID-19), which impact the physical, emotional, and social health of youth with headache disorders. BACKGROUND: COVID-19 has affected societies on a global scale including children and youth with chronic headache disorders. Many concerns are predicted to arise in the 2020-2021 school year, whether classes are conducted in-person or virtually. METHODS: Clinical impressions were combined with a review of the literature, although limited due to the recent nature of this issue. RESULTS: We describe recommendations to support caregivers and youth as they face changes expected with the return to school in the fall of 2020. CONCLUSION: Although there are significant concerns for caregivers and youth with migraine given the context of changes related to the pandemic, there are many recommendations that can help minimize exacerbations of the physical, emotional, and social health of youth with chronic migraine.

Acute Treatments for Episodic Migraine in Adults: A Systematic Review and Meta-analysis.

Importance: Migraine is common and can be associated with significant morbidity, and several treatment options exist for acute therapy. Objective: To evaluate the benefits and harms associated with acute treatments for episodic migraine in adults. Data Sources: Multiple databases from database inception to February 24, 2021. Study Selection: Randomized clinical trials and systematic reviews that assessed effectiveness or harms of acute therapy for migraine attacks. Data Extraction and Synthesis: Independent reviewers selected studies and extracted data. Meta-analysis was performed with the DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction or by using a fixed-effect model based on the Mantel-Haenszel method if the number of studies was small. Main Outcomes and Measures: The main outcomes included pain freedom, pain relief, sustained pain freedom, sustained pain relief, and adverse events. The strength of evidence (SOE) was graded with the Agency for Healthcare Research and Quality Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Findings: Evidence on triptans and nonsteroidal anti-inflammatory drugs was summarized from 15 systematic reviews. For other interventions, 115 randomized clinical trials with 28 803 patients were included. Compared with placebo, triptans and nonsteroidal anti-inflammatory drugs used individually were significantly associated with reduced pain at 2 hours and 1 day (moderate to high SOE) and increased risk of mild and transient adverse events. Compared with placebo, calcitonin gene-related peptide receptor antagonists (low to high SOE), lasmiditan (5-HT1F receptor agonist; high SOE), dihydroergotamine (moderate to high SOE), ergotamine plus caffeine (moderate SOE), acetaminophen (moderate SOE), antiemetics (low SOE), butorphanol (low SOE), and tramadol in combination with acetaminophen (low SOE) were significantly associated with pain reduction and increase in mild adverse events. The findings for opioids were based on low or insufficient SOE. Several nonpharmacologic treatments were significantly associated with improved pain, including remote electrical neuromodulation (moderate SOE), transcranial magnetic stimulation (low SOE), external trigeminal nerve stimulation (low SOE), and noninvasive vagus nerve stimulation (moderate SOE). No significant difference in adverse events was found between nonpharmacologic treatments and sham. Conclusions and Relevance: There are several acute treatments for migraine, with varying strength of supporting evidence. Use of triptans, nonsteroidal anti-inflammatory drugs, acetaminophen, dihydroergotamine, calcitonin gene-related peptide antagonists, lasmiditan, and some nonpharmacologic treatments was associated with improved pain and function. The evidence for many other interventions, including opioids, was limited.

A pilot exploratory study comparing the King-Devick test (KDT) during and between migraine attacks.

BACKGROUND: The King-Devick test is a timed rapid number naming task that involves complex cerebral functions. The objective of this pilot exploratory study is to determine whether there is a difference in the King-Devick test during a migraine attack compared to the interictal phase. METHODS: We evaluated 29 adult subjects with migraine with aura or migraine without aura. For each participant, we performed King-Devick tests during migraine attacks and interictal phases. Subjects served as their own controls. RESULTS: The King-Devick test was slower during the migraine attack compared to the interictal baseline (median 4.6 sec slower, p < 0.001). The slowing of the King-Devick test during migraine attack was more prominent in those with migraine with aura compared to subjects with migraine without aura (median 7.5 vs. 2.8 sec, p = 0.028). CONCLUSIONS: This exploratory, observational study shows changes in the King-Devick test during migraine compared to the interictal phase. Future studies are required to determine if the King-Devick test may be used as a rapid and simple tool to objectively characterize migraine-associated disability.

Pressing Issues Among Trainees and Early Career Physicians in Headache Medicine: Survey Results From the American Headache Society New Investigator and Trainee Section and International Headache Academy.

OBJECTIVE: We surveyed the American Headache Society (AHS) New Investigators and Trainees Section (NITS), and International Headache Academy (IHA) attendees to better understand what they perceive as the most pressing issues for themselves as new investigators and trainees in the field of headache medicine. BACKGROUND: The NITS and IHA are intended as platforms for mentorship, leadership training, and professional development in the field of headache medicine. Identifying and addressing pressing issues among new investigators and trainees based on their perceived needs is critical to encouraging their development and success as headache medicine clinicians and researchers. METHODS: Paper surveys were administered at the NITS meeting at the November 2018 Scottsdale Headache Symposium and the January 2019 IHA. Additionally an online version was sent to the NIT listserv in November of 2018. The survey queried demographic information (gender, race, age, profession, training status, and years in practice) and asked participants to identify their top 3 most pressing issues/questions among a list of options. RESULTS: Fifty-three responses were submitted (53/255; total response rate 20.7%). Among the surveys, 18 in-person responses were from the NITS meeting (18/20; response rate 90.0%), 23 in-person responses were from the IHA (23/45; response rate 51.1%), and 12 responses were from the online survey (12/190; response rate 6.3%). No duplicate responses were submitted based on comparison of demographics. One respondent identified as a researcher exclusively and was excluded from further analyses; the rest identified as clinicians at various levels of medical training. Fifteen respondents were not members of the NITS (28.8%); the most common reason for nonmembership was lack of awareness of the section (92.8%). Overall the most pressing issues/questions included (% of respondents who ranked issue/question among top 3): Career planning (51.9%), Logistics of running a headache clinic (40.4%), and Opportunities for involvement (38.5%). Most pressing issues/questions differed depending on level of training. Working with industry was the most pressing issue/question identified by early career physicians (55.0%). Career planning was the most pressing issue/question among fellows (72.2%) and residents (64.3%). CONCLUSION: Many of the most pressing issues identified by respondents are topics that are not formally addressed in medical and research training.

COVID-19 and Headache Medicine: A Narrative Review of Non-Steroidal Anti-Inflammatory Drug (NSAID) and Corticosteroid Use.

OBJECTIVE: To summarize the current literature on non-steroidal anti-inflammatory drug and corticosteroid use during the coronavirus disease 2019 (COVID-19) pandemic, recognizing that these are commonly used treatments in the field of headache medicine. BACKGROUND: The use of non-steroidal anti-inflammatory drugs and corticosteroids in patients during the COVID-19 pandemic has been a controversial topic within the medical community and international and national health organizations. Lay press and social media outlets have circulated opinions on this topic despite the fact that the evidence for or against the use of these medications is sparse. In the field of headache medicine, these medications are used commonly and both patients and clinicians may have questions or hesitations pertaining to their use during the COVID-19 pandemic. METHODS: A detailed search of the scientific and popular literature was performed. RESULTS: There is limited literature pertaining to the safety of non-steroidal anti-inflammatory drugs and corticosteroids during the COVID-19 pandemic. To date, there are no clear scientific data that preclude the use of non-steroidal anti-inflammatory drugs in the general population who may acquire COVID-19 or in those acutely infected with the virus. Several health organizations have concluded that treatment with corticosteroids during active infection should be avoided due to concerns of prolonged viral shedding in the respiratory tract and the lack of survival benefit based on the data from past coronaviruses and influenza virus; specific exceptions exist including treatment for underlying asthma or chronic obstructive pulmonary disease, septic shock, and acute respiratory distress syndrome. CONCLUSION: Scientific information regarding the COVID-19 pandemic is constantly evolving, and limited or contradictory information can lead to confusion for both patients and clinicians. It is recommended that prior to prescribing non-steroidal anti-inflammatory drugs and steroids for the treatment of headache, clinicians have open discussions with their patients about the potential risks and benefits of using these medications during the COVID-19 pandemic. This manuscript summarizes the currently available evidence and understanding about these risks and benefits to help clinicians navigate such discussions.

Adolescent Perspectives on the Burden of a Parent's Migraine: Results from the CaMEO Study.

OBJECTIVE: To assess the impact of parental migraine on adolescents (aged 13-21 years) living within the parental home from the adolescent's perspective. BACKGROUND: Family members are affected by their parent's migraine. We surveyed adolescents on the social, academic, and emotional effects of their parent's migraine. METHODS: The Chronic Migraine Epidemiology and Outcomes (CaMEO) study was a longitudinal Web-based study with cross-sectional modules designed to assess migraine symptoms, severity, frequency, and disability; migraine-related consulting practices, healthcare utilization, medication use, comorbid health conditions, and family related burden associated with migraine. The Family Burden Module (adolescent version; FBM-A) from the CaMEO study assessed parents with migraine and adolescent household members (dyads). Adolescents ranged in age from 13-21 years and were living at home with their parent. The initial FBM-A survey included 52 items covering five domains, which was refined and reduced by confirmatory factor analysis to 36 items covering four domains. Depression (9-item Patient Health Questionnaire) and anxiety (7-item Generalized Anxiety Disorder scale) were assessed. Item responses were stratified by parent migraine status (episodic migraine [EM], <15 headache days/month; chronic migraine [CM], ≥15 headache days/month). Frequencies of activities/events missed because of parental headache were categorized as ≥1 time or ≥4 times/previous 30 days. RESULTS: The sample included 1,411 parent-adolescent dyads (parent with EM, n = 1,243 [88.1%]; parent with CM, n = 168 [11.9%]). Burden due to a parent's migraine was reported in four domains based on 36 items including: Loss of Parental Support and Reverse Caregiving (5 items); Emotional Experience (13 items); Interference with School (4 items); and Missed Activities and Events (14 items). Across domains, perceived burden was greater for adolescents of parents with CM vs EM. Rates of moderate-to-severe anxiety symptoms were higher among adolescents of parents with CM (6.2 vs 11.3%, P = .01), while moderate-to-severe depression symptom rates were similar (5.5 vs 8.9%, P = .08). More adolescents of CM vs EM parents reported having a headache within the previous 3 months (P < .001). CONCLUSIONS: Parental migraine negatively impacts adolescent children, extending our understanding of the family burden of migraine and emphasizing the potential benefit to children of optimizing migraine care.

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing-like attacks in a pediatric patient found to have a pontine capillary telangiectasia and developmental venous anomaly: A case report exploring the root of the problem.

Introduction Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)-like attacks are rarely reported in the pediatric population and may remain undiagnosed and under-investigated as a result. Case presentation We present a case of a 15-year-old male with intermittent, episodic, right-sided brief headaches most in keeping with SUNCT, initially diagnosed as paroxysmal hemicrania, but with no response to indomethacin. The pain was likewise not responsive to typical migraine treatments or steroids. Management and outcome Contrast-enhanced magnetic resonance imaging demonstrated a right pontine capillary telangiectasia with an associated developmental venous anomaly that was adjacent to the root of the right trigeminal nerve. Differential diagnosis included first division trigeminal neuralgia with autonomic features. The patient's pain was partially alleviated by oxygen administration and responded well to carbamazepine; he remained pain free on carbamazepine a year later. Conclusion This case highlights the diagnostic dilemma of differentiating SUNCT from trigeminal neuralgia with autonomic features, both of which are rare diagnoses in pediatric patients, and the importance of appropriate neuroimaging to rule out secondary causes in patients presenting with trigeminal autonomic cephalalgias, recognizing that abnormalities identified on neuroimaging, such as vessels adjacent to the trigeminal nerve, may not be causative findings.

Safety of Triptans in Patients Who Have or Are at High Risk for Cardiovascular Disease: A Target Trial Emulation.

OBJECTIVE: To evaluate the safety of triptans in migraine patients with cardiovascular disease or elevated cardiovascular risk. PATIENTS AND METHODS: We retrieved data from a multistate US-based health system (January 2000 to August 2022) on adults with migraine and confirmed cardiovascular/cerebrovascular disease, or at least two cardiovascular risk factors. We compared the effect of triptans to nontriptan treatments on major adverse cardiovascular events (MACE) and its components at 60 days of starting treatments. We emulated a target trial and used propensity score matching for analysis. RESULTS: The 3518 patients in the triptan group were matched to the 3518 patients in the nontriptan group (median age, 55 years; 80.60% female). At 60 days, 52 patients (1.48%) in the triptan group had MACE, compared with 13 patients (0.37%) in the nontriptan group (relative risk [RR], 4.00; 95% CI, 2.24 to 7.14). Patients treated with triptans also had significantly higher risk of nonfatal myocardial infarction (15 patients (0.43%) vs 0 patients (0.00%)); heart failure (RR, 4.50; 95% CI, 1.91 to 10.61); and nonfatal stroke (RR, 8.00; 95% CI, 1.00 to 63.96). Five patients (0.14%) in each group died. The findings were consistent when analyses were restricted to sumatriptan, oral administration of triptan, patients with chronic migraine, history of cardiovascular disease, or history of cerebrovascular disease. CONCLUSION: Triptans likely increase the risk of MACE; however, the incidence of MACE remains low in migraine patients with cardiovascular disease or elevated cardiovascular risk. TRIAL REGISTRATION: Treatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk and in Pregnant Women. CLINICALTRIALS: gov Identifier: NCT05854992 (https://classic. CLINICALTRIALS: gov/ct2/show/NCT05854992).

Profile of Lasmiditan in the Acute Treatment of Migraine in Adults: Design, Development, and Place in Therapy.

Migraine is a common neurological disorder that is present in a large proportion of the global population. It is estimated to occur in around 20.7% of women and 10.7% of men in the United States. The pathophysiology of migraine is a major focus of research, and medications have been developed to interrupt the processes that generate headache and other bothersome symptoms of migraine attacks. The triptan class of medications acts as a direct agonist at the 5-HT1B/D receptor but its use is limited by contraindications for those with coronary or cerebrovascular disease. Lasmiditan is a first-in-class agonist at the 5-HT1F serotonin receptor that does not appear to generate vasoconstriction. This article reviews the design, development, and place in therapy for lasmiditan. A narrative review of the literature using the Ovid MEDLINE database was performed. The rationale behind the development of lasmiditan and pre-clinical, proof-of-concept, Phase II, pivotal, Phase III trials and post-hoc data is covered. Additionally, the efficacy and safety of lasmiditan when compared to other acute treatments in migraine is described, including lasmiditan's side effect profile and status as a Schedule V substance. Further, head-to-head studies of lasmiditan compared with other acute treatments are required.