INTRODUCTION:Cluster headache is an extremely painful and severely disabling primary headache disorder that, despite its profound impact on quality of life, remains underdiagnosed and undertreated. Effective management requires a structured approach across the cluster cycle, but practical, timeline-based guidance integrating established and emerging therapies is lacking. AREAS COVERED:The authors present a treatment framework organized by clinical timeline: inter-cycle period, cycle onset, active cycle, and resolution, addressing acute abortive, bridge, and prophylactic therapies with evidence quality, dosing, and monitoring. Both established synthetic agents and recently recognized biologic therapies are examined, with particular focus on anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies and forward-looking targets such as PACAP and 5-HT2A. References were identified through searches of PubMed and clinical trial registries from inception to June 2026. EXPERT OPINION:Anti-CGRP monoclonal antibodies are a meaningful advance, best positioned as an adjunct to established prophylaxis rather than a replacement. PACAP-targeted therapy is a promising direction whose role in cluster headache remains to be defined. The serotonergic agent psilocybin warrants closer attention, as its early therapeutic signal merits rigorous investigation despite the legal and historical barriers constraining its study.

OBJECTIVE:The current study aimed to evaluate the remote electrical neuromodulation (REN) wearable device over 3 years, assessing the potential for tachyphylaxis, consistent effectiveness, overall utilization patterns, and safety. BACKGROUND:Migraine is a highly prevalent chronic neurological disease, especially during peak years of productivity, requiring ongoing management to prevent and reduce its disability. Traditional treatments often face challenges with long-term adherence due to waning efficacy, side effects, and medication interactions. REN offers a nonpharmacological approach for acute and preventive migraine treatment. METHODS:This prospective real-world cohort study analyzed data from 224 patients with migraine in the United States who consistently treated their migraine attacks with the REN wearable device for 3 years between December 2019 and September 2024. The primary endpoint was defined as lack of tachyphylaxis, aka an increase of no more than 2.5 intensity units on a scale of 100 units between 2 consecutive years, representing a nonclinically meaningful change in treatment intensity over 3 years. Secondary endpoints were consistent effectiveness in at least 50% of treatments and consistent utilization, compared over 3 years. The safety outcome assessed the proportion of users with device-related adverse events (dAEs) and the severity and seriousness of the dAEs. RESULTS:Over 3 years, there was no clinically meaningful change in treatment intensity, and the average (± standard deviation, SD) change between 2 consecutive years was no more than 2.5 intensity units (1.8 ± 5.5 between years 1 and 2, and 1.4 ± 5.3 between years 2 and 3; p = 0.120, McNemar test for two related dichotomous variables), indicating no tachyphylaxis. Effectiveness endpoints remained consistent over 3 years of treated attacks (generalized linear mixed model of repeated measures categorical data) with no significant differences over the 3 years: 72.1%-76.8% of users reporting pain relief (p = 0.846), 26.8%-28.7% pain freedom (p = 0.966), 65.3%-70.8% functional disability relief (p = 0.749), 31.4%-38.9% functional disability freedom (p = 0.680), 29.0%-37.0% freedom from photophobia (p = 0.590), 37.9%-49.4% freedom from phonophobia (p = 0.534), and 57.1%-66.7% freedom from nausea/vomiting (p = 0.753). Monthly utilization was consistent, ranging between 8.0 and 8.8 treatments per month, suggesting sustained adherence to therapy (p = 0.337, generalized linear model of repeated measures). Only two (0.9%) expected, nonserious dAEs were reported (mild or moderate localized skin reactions), neither leading to treatment discontinuation. CONCLUSION:This study demonstrates the long-term safety, consistent utilization, and acute treatment effectiveness, with no tachyphylaxis, in patients with migraine consistently treating with REN for 3 years. This suggests that REN offers an effective, well-tolerated, safe, and sustainable long-term treatment option for individuals with migraine.

Migraine headache is highly prevalent and the most common neurologic disorder, affecting one billion people worldwide. It is also the most disabling condition in people under 50, with a huge impact on working ability, family, and social life. Access to effective preventive medication is important and may be considered if the patient has 6 or more migraine days per month, ineffective abortive agents, or disability on 2 or more days per month. Propranolol, metoprolol, candesartan, topiramate, divalproex, lisinopril, amitriptyline, and venlafaxine have the strongest evidence to support for use. Flunarizine and pizotifen may also be effective. Selection of preventive treatments is based on individual characteristics, comorbid conditions, efficacy, contraindications, side effects, cost, compliance, and drug. An adequate trial of migraine prophylaxis is usually 2 months at the target dose, and it is always important to re-evaluate indication for prophylactic use after a period of time.

Measure migraine-related stigma among people living with migraine across multiple countries.

Comments, Observations, and Rebuttals The Effect of Onabotulinum Toxin on Aura Frequency and Severity in Patients With Hemiplegic Migraine – A Comment William B. Young MD, Thomas Jefferson University Hospital – Neurology, 900 Walnut Street, Suite 200, Philadelphia, PA, 19107 USASearch for more papers by this author William B. Young MD, Thomas Jefferson University Hospital – Neurology, 900 Walnut Street, Suite 200, Philadelphia, PA, 19107 USASearch for more papers by this author First published: 21 December 2018 https://doi.org/10.1111/head.13445Citations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume59, Issue1January 2019Pages 110-110 RelatedInformation

Background and Objectives: The burden of chronic headache disorders in the United States is substantial. Some patients are treatment refractory. Ketamine, an N-methyl-D-aspartate antagonist, provides potent analgesia in subanesthetic doses in chronic pain, and limited data suggest it may alleviate headache in some patients. Methods: We performed a retrospective study of 61 patients admitted over 3 years for 5 days of intravenous therapy that included continuous ketamine to determine responder rate and patient and ketamine infusion characteristics. Pain ratings at 2 follow-up visits were recorded. An immediate responder was a patient with decrease of 2 points or greater in the numerical rating scale (0-10) from start to final pain in the hospital. Sustained response at office visits 1 and 2 was determined based on maintaining the 2-point improvement at those visits. Patients were assessed daily for pain and adverse events (AEs). Results: Forty-eight (77%) of the 61 patients were immediate responders. There were no differences regarding demographics, opioid use, or fibromyalgia between immediate responders and nonresponders. Maximum improvement occurred 4.56 days (mean) into treatment. Sustained response occurred in 40% of patients at visit 1 (mean, 38.1 days) and 39% of patients at visit 2 (mean, 101.3 days). The mean maximum ketamine rate was 65.2 +/- 2.8 mg/h (0.76 mg/kg per hour). Ketamine rates did not differbetween groups. Adverse events occurred equally in responders and nonresponders and were mild. Conclusions: Ketamine was associated with short-term analgesia in many refractory headache patients with tolerable adverse events. A prospective study is warranted to confirm this and elucidate responder characteristics.

Vox Clamantis De-Stigmatizing Migraine – With Words William B. Young MD, Corresponding Author William B. Young MD william.b.young@jefferson.edu Thomas Jefferson University, Jefferson Hospital for Neuroscience, Philadelphia 19107, PA, USAAddress all correspondence to W.B. Young, Thomas Jefferson University, Jefferson Hospital for Neuroscience, 900 Walnut Street, Suite 200, Philadelphia, PA 19107, email: william.b.young@jefferson.eduSearch for more papers by this author William B. Young MD, Corresponding Author William B. Young MD william.b.young@jefferson.edu Thomas Jefferson University, Jefferson Hospital for Neuroscience, Philadelphia 19107, PA, USAAddress all correspondence to W.B. Young, Thomas Jefferson University, Jefferson Hospital for Neuroscience, 900 Walnut Street, Suite 200, Philadelphia, PA 19107, email: william.b.young@jefferson.eduSearch for more papers by this author First published: 15 November 2017 https://doi.org/10.1111/head.13209Citations: 10 Conflict of Interest: None. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume58, Issue2February 2018Pages 319-321 RelatedInformation

The following article is a Thomas Jefferson Headache Center headache rounds presentation. A 37-year-old woman, who reports a history of chronic sinusitis, developed sudden onset headache 1 1/2 years prior to her initial presentation at the Jefferson Headache Center. At that time she noted acute severe pressure-like pain bilaterally in her neck, which radiated to her forehead above her eyebrows. She denied fever, rashes, or nasal discharge at the time. The pain was much more intense than her usual “sinus headaches” and associated with a positional component, occurring only upon standing, reaching a peak intensity of 10/10 that would only last seconds and remaining as a dull milder continuous frontal pain for up to 12 hours. She had nausea and vomiting but no photophobia, phonophobia, or osmophobia. There was no rhinorrhea, conjuctival injection, or eye tearing. The pain was alleviated upon lying down. After several emergency department visits, a head computed tomography was performed revealing chronic sinus disease that led her to sinus surgery with no improvement of symptoms. For several months, she was unsuccessfully treated with preventive therapy including topiramate, duloxetine, gabapentin, onabotulinumtoxin A, and abortive therapy including triptans, nonsteroidal anti-inflammatory drugs, barbiturates, and muscle relaxants. Acupuncture and occipital nerve blocks provided limited relief. The patient denied a prior medical and family history of migraines. Since the onset of symptoms, the patient continued to have intermittent explosive frontal headaches that would be triggered by standing and improved upon lying down. As time elapsed, she also noticed suboccipital pain and neck discomfort worsened by Valsalva maneuvers such as straining and coughing. She also reported bilateral upper extremity paresthesias along with subjective weakness.

Background: Malignant MCA infarction is a devastating disease representing 1-10% of strokes. Evidence from recent randomized controlled trials show improved survival and functional outcomes following decompressive hemicraniectomy (DHC) compared with optimal medical. Ideal patient selection remains somewhat controversial. The current study examines the effects of demographic and clinical variables on functional outcomes in patients surviving one or more years following DHC. Methods: We retrospectively reviewed patients who underwent DHC for malignant MCA infarction at our institution from 03/2006 to 04/2012. We collected and compared demographic and clinical variables including age, gender, race, timing of DHC, side of infarction, IV TPA administration, and additional cerebral territorial involvement (ACA or PCA). The mean mRs was calculated for each group and the Wilcoxon-Mann-Whitney two tailed test was used to calculate statistical significance. Results: A total of 32 patients met inclusion/exclusion criteria. There was no statistical difference in functional outcomes between patients ≤60 years of age and those >60 years (p=0.51). No statistical difference was observed between males and females (p=0.84)). Patients who received their DHC within 48 hours of their stroke were more likely to have a better outcome than patients who received DHC after 48 hours (p=0.024). Other variables including race, cerebral dominance involvement, IV TPA administration, or additional cerebral territory involvement did not show statistical significance with respect to functional outcomes (p=0.22, p=0.462, p=0.597, and p=0.614 respectively). Conclusion: In this retrospective study, early DHC done within 48 hours of stroke was the only clinical variable shown to improve functional outcomes 1 year or more later among survivors of patients receiving DHC for malignant MCA infarction. No difference in functional outcome was seen based on age, gender, race, IV TPA administration, dominant MCA involvement, and additional cerebral territorial co infarction. Patient selection should be individualized and larger studies are needed to better assess this patient population, especially in the elderly.

OBJECTIVE: To validate a working definition of alcohol-sensitive migraine. BACKGROUND: Studying alcohol-induced headache and migraine offers a unique opportunity to better understand migraine triggers. We have previously proposed a working definition of alcohol-induced headache and validated it with a survey questionnaire. DESIGN/METHODS: Cross-sectional structured interview study. RESULTS: We applied the working definition of alcohol sensitivity to the patients following the interview study. Of the 224 completed interviews in women with migraines, 37.5% were found to be alcohol-sensitive, 49.6% alcohol-intermediate, and 12.9% alcohol-insensitive subjects. The average age of the participants was 42.4 ± 12 years old. Alcohol-sensitive patients tended to be older in age, and they demonstrated a higher frequency of characteristic migraine traits such as nausea (81%, p=0.03) and phonophobia (84%, p=0.03) when compared to the alcohol-intermediate and alcohol-insensitive groups. Additionally, alcohol-sensitive patients had a greater chance of having one or more dietary triggers (p=0.019). Comparing episodic to chronic migraineurs, we found no significant difference between the percentages in the three sensitivity groups. Relating the patient's self-perceived sensitivity level to the alcohol sensitivity scale, 60.7% of the alcohol-sensitive patients correctly identified themselves as such, 57.7% of the alcohol-intermediate group identified themselves as intermediately sensitive, and 100% of the alcohol-insensitive group evaluated themselves to be not sensitive to alcohol as a migraine trigger. CONCLUSIONS: The proposed alcohol sensitivity scale is shown to be operational in a clinic setting. This should allow for more sound studies of alcohol as a migraine trigger, providing insight into the mechanism of action of migraine triggers.

OBJECTIVE: This is a case report on a patient who develolped ischemic stroke after initiation of DHE for management of a migraine-like headache resembling reversible cerebral vasoconstriction syndrome (RCVS). BACKGROUND: DHE and its therapeutic efficacy in management of migraines has been highly studied with only a few studies delineating the side effects of the medication. The only highly proven contraindication in literature is one of DHE and patients with known coronary artery disease.There are case reports linking some patients having limb threatening ischemia6, ischemic bowel diseas, transient global amnesia, and cervico-cerebral vasospasm. DESIGN/METHODS: Case report. RESULTS: JM is a 53 year old man with stroke risk factors only significant for tobacco use who was admitted for management of status migranousus continuous since a thunderclap onset, CT, LP , and initial MRI were all negative. After failing multiple therapies he was treated with IV DHE. He awoke shortly after the administration of the fifth dose of DHE with acute onset of right sided hemiplegia and subsequently underwent an MRI of brain showing development of an acute right basal ganglia and corona radiata infarct. A stroke workup including cerebral angiography and 2D-echo was normal. Patient was discharged to rehab and has limited strenght in right hemibody. His severe unilateral right sided headache with all associated features of migraine persists 6 months since the headache onset. CONCLUSIONS: We report this case of a Stroke occuring in a patient who failed conventional outpatient management of sudden onset migraine-like headache that we suspect may have been on the spectrum of RCVS. Prior to this no reports have been published on a stroke possibly being a side effect or complication of DHE therapy. One prior report has suggested DHE caused RCVS in a migraine patient on citalopram, supporting the concept that DHE should be avoided in the setting of recent onset RCVS. Disclosure: Dr. Ghafoor has nothing to disclose. Dr. Young has received personal compensation for activities with Merck & Co. Inc. as a speaker and advisory board member, and with Allergan Inc., GlaxoSmithKline Inc., and Zogeniz/Astellas as a speaker. Dr. Young has received research support from Medtronic Inc.