Ailani, Jessica

Background The American Registry for Migraine Research (ARMR) is a multicenter, prospective, longitudinal patient registry, biorepository, and neuroimaging repository that collects clinical data, electronic health record (EHR) data, blood samples, and brain imaging data from individuals with migraine or other headache types. In this manuscript, we outline ARMR research methods and report baseline data describing an initial cohort of ARMR participants. Methods Adults with any International Classification of Headache Disorders (ICHD) diagnosis were prospectively enrolled from one of the 8 participating headache specialty centers. At baseline, ARMR participants complete web‐based questionnaires, clinicians enter the participant’s ICHD diagnoses, an optional blood specimen is collected, and neuroimaging data are uploaded to the ARMR neuroimaging repository. Participants maintain the ARMR daily headache diary longitudinally and follow‐up questionnaires are completed by participants every 3 months. EHR data are integrated into the ARMR database from a subset of ARMR sites. Herein, we describe the ARMR methodology and report the summary data from ARMR participants who had, from February 2016 to May 2019, completed at least 1 baseline questionnaire from which data are reported in this manuscript. Descriptive statistics are used to provide an overview of patient’s sociodemographics, headache diagnoses, headache characteristics, most bothersome symptoms other than headache, headache‐related disability, comorbidities, and treatments. Results Data were available from 996 ARMR participants, enrolled from Mayo Clinic Arizona, Dartmouth‐Hitchcock Medical Center, University of Utah, University of Colorado, Thomas Jefferson University, University of Texas Health Science Center at Houston, Georgetown University Medical Center, and DENT Neurological Institute. Among ARMR participants, 86.7% (n = 864) were female and the mean age at the time of enrollment was 48.6 years (±13.9; range 18‐84). The most common provider‐reported diagnosis was chronic migraine (n = 622), followed by migraine without aura (n = 327), migraine with aura (n = 196), and medication overuse headache (n = 65). Average headache frequency was 19.1 ± 9.2 days per month (n = 751), with 68% reporting at least 15 headache days per month. Sensitivity to light was the most frequent (n = 222) most bothersome symptom overall, other than headache, but when present, cognitive dysfunction was most frequently (n = 157) the most bothersome symptom other than headache. Average migraine disability assessment (MIDAS) score was 52 ± 49 (n = 760), (very severe headache‐related disability); however, 17% of the ARMR population had MIDAS scores suggesting “no” or “mild” disability. The most common non‐headache health issues were allergies (n = 364), back pain (n = 296), neck pain (n = 296), depression (n = 292), and anxiety (n = 278). Nearly 85% (n = 695) of patients were using preventive medications and 24.7% were using non‐medication preventive therapy (eg, vitamins and neuromodulation). The most common preventive medication classes were neurotoxins, anticonvulsants, antidepressants, vitamins/supplements, and anticalcitonin gene‐related peptide ligand or receptor‐targeted monoclonal antibodies. Nearly 90% (n = 734) of ARMR participants was taking medications to treat migraine attacks, with the most common classes being triptans, non‐steroidal anti‐inflammatory drugs, antiemetics, acetaminophen, and combination analgesics. Conclusions ARMR is a source of real‐world patient data, biospecimens, and brain neuroimaging data that provides comprehensive insight into patients with migraine and other headache types being seen in headache specialty clinics in the United States. ARMR data will allow for longitudinal and advanced analytics that are expected to lead to a better characterization of patient heterogeneity, healthcare resource utilization, identification of endophenotypes, factors that predict treatment outcomes and clinical course, and ultimately advance the field toward precision headache medicine.

Objective To evaluate onset of effect of galcanezumab in patients with episodic migraine. Background Galcanezumab is a monoclonal antibody that binds to calcitonin gene‐related peptide and is indicated for preventive treatment of migraine. Design/Methods Data on the primary outcome measure were analyzed from 2 previously published double‐blind, Phase 3 studies (EVOLVE‐1 [N = 858] and EVOLVE‐2 [N = 915]) wherein adult patients with episodic migraine were randomized to receive monthly subcutaneous injections of galcanezumab 120 mg (with 240‐mg loading dose) or 240 mg or placebo for up to 6 months. Monthly onset of effect was defined as the earliest month at which galcanezumab achieved and subsequently maintained statistical superiority to placebo on the mean change from baseline in the number of monthly migraine headache days (MHDs). If onset occurred in Month 1, weekly onset was evaluated and defined as the earliest week at which galcanezumab statistically separated from placebo and maintained statistical separation for remaining weeks in that month. Day of onset of effect was also analyzed, as were monthly and weekly onset, for occurrence of ≥50% reduction from baseline in number of MHDs. Results For both studies, change from baseline in monthly MHDs showed a statistically significant separation of galcanezumab from placebo at Month 1 and each subsequent month (each P < .001). Analysis of the first month for both studies indicated onset of effect in the first week, with galcanezumab‐treated patients having significantly higher odds of having fewer MHDs in the first week (odds ratio [95% confidence interval] for EVOLVE‐1, 2.71 [2.00, 3.66], and for EVOLVE‐2, 2.88 [2.16, 3.86]; both P < .001) and each subsequent week compared with placebo‐treated patients ( P ≤ .004). Daily analysis showed onset of effect at Day 1 (first day after injection day). Galcanezumab also demonstrated superiority to placebo on occurrence of ≥50% reduction in MHDs starting at Week 1 (percentage of patients with 50% response in galcanezumab group vs placebo group for EVOLVE‐1, 54.3% vs 32.4% [ P < .001], and for EVOLVE‐2, 59.4% vs 38.0% [ P < .001]). Conclusion Rapid onset of preventive effect on the first day after injection of galcanezumab was confirmed in both studies of episodic migraine.

Headache disorders are among the most common and disabling medical conditions worldwide. Pharmacologic acute and preventive treatments are often insufficient and poorly tolerated, and the majority of patients are unable to adhere to their migraine treatments due to these issues. With improvements in our understanding of migraine and cluster headache pathophysiology, neuromodulation devices have been developed as safe and effective acute and preventive treatment options. In this review, we focus on neuromodulation devices that have been studied for migraine and cluster headache, with special attention to those that have gained food and drug administration (FDA) clearance. We will also explore how these devices can be used in patients who might have limited pharmacologic options, including the elderly, children, and pregnant women.

The sphenopalatine ganglion (SPG) has attracted the interest of practitioners treating head and face pain for over a century because of its anatomical connections and role in the trigemino‐autonomic reflex. In this review, we discuss the anatomy of the SPG, as well as what is known about its role in the pathophysiology of headache disorders, including cluster headache and migraine. We then address various therapies that target the SPG, including intranasal medication delivery, new SPG blocking catheter devices, neurostimulation, chemical neurolysis, and ablation procedures.

Objective To survey neurology residency program directors (PDs) on trainee exposure, supervision, and credentialing in procedures widely utilized in headache medicine. Background Clinic‐based procedures have assumed a prominent role in headache therapy. Headache fellows obtain procedural competence, but reliance on fellowship‐trained neurologists cannot match the population eligible for treatments. The inclusion of educational modules and mechanisms for credentialing trainees pursuing procedural competence in residency curricula at individual programs is not known. Methods A web‐based survey of US neurology residency PDs was designed by the American Headache Society (AHS) procedural special interest section in collaboration with AHS and American Academy of Neurology's Headache and Facial Pain section leadership. The survey addressed exposure, training, and credentialing in: (1) onabotulinumtoxinA (onabotA) injections, (2) extracranial peripheral nerve blocks (PNBs), and (3) trigger point injections (TPIs). Results Fifty‐five PDs (42.6%) completed the survey. Compared to noncompleters, survey completers were more likely to feature headache fellowships at their institutions (38.2% vs 10.8%, P =0.0002). High exposure (onabotA=90.9%, PNBs=80.0%, TPIs=70.9%) usually featured hands‐on patient instruction (66.2%) and lectures (55.7%). Supervised performance rates were high (onabotA=65.5%, PNBs=60.0%, TPIs=52.7%), usually in continuity clinic (60.0%) or headache elective (50.9%). Headache specialists (69.1%) or general neurology (32.7%) faculty most commonly trained residents. Formal credentialing was uncommon (16.4‐18.2%), mostly by documenting supervised procedures (25.5%). Only 27.3% of programs permitted trainees to perform procedures independently. Most PDs felt procedural exposure (80.0‐90.9%) and competence (50.9‐56.4%) by all trainees was important. Conclusions Resident exposure to procedures for headache is high, but credentialing mechanisms, while desired by most PDs, are not generally in place. Implementation of a credentialing process may ensure trainees enter practice with the ability to perform procedures safely and effectively.

Objective To describe a standardized methodology for the performance of peripheral nerve blocks ( PNB s) in the treatment of headache disorders. Background PNBs have long been employed in the management of headache disorders, but a wide variety of techniques are utilized in literature reports and clinical practice. Methods The A merican H eadache S ociety S pecial I nterest S ection for PNBs and other I nterventional P rocedures convened meetings during 2010‐2011 featuring formal discussions and agreements about the procedural details for occipital and trigeminal PNBs . A subcommittee then generated a narrative review detailing the methodology. Results PNB indications may include select primary headache disorders, secondary headache disorders, and cranial neuralgias. Special procedural considerations may be necessary in certain patient populations, including pregnancy, the elderly, anesthetic allergy, prior vasovagal attacks, an open skull defect, antiplatelet/anticoagulant use, and cosmetic concerns. PNBs described include greater occipital, lesser occipital, supratrochlear, supraorbital, and auriculotemporal injections. Technical success of the PNB should result in cutaneous anesthesia. Targeted clinical outcomes depend on the indication, and include relief of an acute headache attack, terminating a headache cycle, and transitioning out of a medication‐overuse pattern. Reinjection frequency is variable, depending on the indications and agents used, and the addition of corticosteroids may be most appropriate when treating cluster headache. Conclusions These recommendations from the A merican H eadache S ociety S pecial I nterest S ection for PNBs and other I nterventional P rocedures members for PNB methodology in headache disorder treatment are derived from the available literature and expert consensus. With the exception of cluster headache, there is a paucity of evidence, and further research may result in the revision of these recommendations to improve the outcome and safety of these interventions.