Background and aims New daily persistent headache (NDPH) is a primary headache disorder characterized by the abrupt onset of continuing and unremitting headache within 24 h of onset. Diagnosis is clinical, requiring exclusion of secondary causes, with limited imaging and treatment data. We assessed the prevalence of nonspecific white matter hyperintensities (WMH) and treatment response in a large retrospective cohort with primary NDPH. Methods A retrospective chart review was conducted on 328 patients diagnosed with NDPH by a headache subspecialist over an 8.5-year period. Patients were classified into the migraine phenotype (MP; n = 260) or tension-type phenotype (TTP; n = 50) based on associated features. The presence of WMH reported on MRI scans and acute and preventive treatment responses were evaluated. Results WMH were reported in 20.9% of MP patients (33/158) and 18.0% of TTP patients (9/50), p = .658. Acute treatments for the MP and TTP were minimally, if at all, effective. Preventive treatments generally had limited effectiveness. For the MP, the percentages of patients achieving a 30% or greater reduction in headache days per month were the following: desvenlafaxine, 54.5%; venlafaxine, 41.2%; and onabotulinumtoxinA, 27.9%. Venlafaxine was the most effective for the TTP with 25% having a 30% or greater reduction in headache days. Greater occipital and pericranial nerve blocks were mildly effective while surgical procedures were largely ineffective. Up to five day inpatient intravenous regimens with dihydroergotamine produced temporary benefit in 41.7%. Conclusions WMH are present in a minority of NDPH patients. Acute treatment is largely not effective. Preventive treatments were more effective in those with MP than TTP with many failures. Future prospective studies with new treatments are needed to identify effective interventions for this often disabling and refractory disorder.

Background Behavioral interventions for people with headache (HA) diseases have demonstrated clinical efficacy. Despite strong empirical support and endorsement by professional practice organizations, behavioral interventions are not widely accessible to HA patients. Clinic-based behavioral treatments remain inaccessible to many. The objectives of this study are to conduct a pilot randomized controlled trial and to determine the feasibility of the implementation of a cognitive behavioral therapy protocol for HA (CBT-HA) delivered via telehealth (TENACITY) compared to enhanced HA usual treatment (EHUT). Methods/design TENACITY is a single-blinded, randomized, controlled, pilot trial with a single intervention arm and an EHUT control arm analyzed as intention-to-treat. This multi-site study had a 31-day run-in/screening period to confirm chronic migraine and an approximately 12-week CBT-HA treatment period. Follow-up assessments were conducted at 3- and 6-month post-treatment initiation. Analysis plan The primary outcome will be analyzed as the change in self-reported number of HA days from the 30-day baseline run-in period before treatment to the number of self-reported days at 3 months post-treatment using a generalized mixed effects model. Secondary outcomes at 3- and 6-month post-treatment will be analyzed in addition. Trial Registration IRP 20-002, TENACITY: Telemedicine-based cognitive therapy for migraine NCT04613362

Introduction Cluster headache is an extremely debilitating and often difficult-to-treat headache disorder characterized by recurrent attacks of excruciating pain associated with cranial autonomic symptoms. Several invasive neuromodulation procedures have been evaluated in the past, but the combination of these procedures to maximize response has not been studied in groups of patients. Materials and methods In this single-center, retrospective, observational study, we present the long-term clinical evolution of seven patients suffering from refractory chronic cluster headache (CCH), treated with combined sphenopalatine ganglion (SPG) and greater occipital nerve (GON) invasive stimulation, ipsilateral to the side of the pain, between February 2010 and March 2021. The Visual Analogue Scale (VAS) and Headache Impact Test (HIT-6) were used to monitor the response. Results The mean follow-up time was 5.8 years ± 3.4 years (maximum 10.4 years). Six out of the seven patients experienced good-to-excellent initial pain relief and achieved almost complete remission of symptoms afterwards. Mean VAS and HIT-6 score values decreased significantly and steadily during most of the observation period. Electrode migration requiring reintervention occurred in two patients. Conclusion Synergistic invasive SPG-GON stimulation is a relatively safe and promising alternative for effective and long-lasting control of CCH. Further studies involving larger samples are warranted.

Background Cluster headache is an excruciating condition for which standard treatments are usually insufficient. Evidence has accumulated that serotonergic psychedelic indoleamines including psilocybin and LSD can be effective in preventing attacks. Methods In this case series, nine patients with episodic and chronic cluster headache that didn’t respond to conventional treatments were treated at a clinic with psilocybin or LSD, under compassionate use provisions, and in most cases separately with ketamine. Results All patients responded positively to at least one of the treatments, and eight of nine responded positively to the treatment with the psychedelic indoleamines, in several cases with extended periods free of attacks. Conclusion These clinical data, though of an exploratory nature, add to the existing pool of evidence for the usefulness of these substances for treating cluster headache, and further support the lowering of legal and regulatory barriers to medical access to the psychedelic indoleamines.

Introduction To investigate the association of genetically predicted migraine with the risk of primary open-angle glaucoma (POAG). Methods To estimate the shared genetic basis of migraine and POAG, we conducted genome-wide genetic correlation analyses using cross-trait linkage disequilibrium score regression. To assess potential causal effects of migraine on POAG risk, we conducted two-sample Mendelian randomization (MR) analyses using data from European ancestry individuals. Genetic instruments (N = 54 genetic variants with minor allele frequency (MAF) ≥ 0.01) were derived from our previous genome-wide association study (GWAS) of migraine conducted in the UK Biobank (16,709 migraine cases and 438,178 controls). For POAG, we used GWAS summary statistics from our previous GWAS conducted in the GERA cohort (3836 POAG cases and 48,065 controls) or using data from the International Glaucoma Genetics Consortium (15,229 POAG cases and 177,473 controls). The inverse-variance weighted (IVW) method was our primary source of MR estimates and common sensitivity analyses were conducted. Results We found that migraine was not genetically associated with POAG ( r g = 0.05; SE = 0.11; P = 0.69). Further, we did not detect any evidence of association between genetically predicted migraine with POAG. Conclusion Our results provide evidence that genetic risk for migraine may not be a strong causal risk factor for POAG.

Background Chronic cluster headache (CH) affects around one in 10,000 people, some of them are resistant to a multitude of treatments. Case We present a case report of a patient with treatment resistant chronic CH which has significantly improved in the setting of gender-affirming care and hormonal treatment with cyproterone acetate and estradiol. Conclusion The case contributes to a growing body of literature suggesting that hormonal factors may impact the clinical course of primary headache disorders, including CH. Particularly in the context of transgender patients and hormone replacement therapy, hormonal modulation may offer an adjunct or alternative approach for managing chronic and treatment-resistant headaches.

Aim Abdominal migraine is rare in adults resulting in a lack of evidence-based treatment recommendations. Treatment therefore pragmatically follows the guidelines for migraine with and without aura. Here, we present the first report of a patient with abdominal migraine successfully treated with three different drugs targeting calcitonin gene-related peptide (CGRP). Methods A 68-year-old woman was referred to our headache center with suspected late-onset abdominal migraine. After extensive diagnostics, the diagnosis was confirmed based on the International Headache Society diagnostic criteria and guideline-compliant treatment was initiated. Results Before treatment initiation, the patient had suffered from 9 to 17 stereotypical episodes per month that lasted about 12 h and included moderate to severe abdominal pain, diarrhea, nausea, and vomiting for over 20 years. Earlier treatment comprised several acute and preventive drugs without success. Finally, she received attack treatment with rimegepant resulting in pain freedom after 2 h and preventive treatment with eptinezumab and fremanezumab resulting in 61% and 78% reduction of the attack frequency, respectively. Conclusion Calcitonin gene-related peptide is a crucial factor for the development of abdominal migraine and CGRP-targeting drugs may be a treatment option for these patients.

Since the high burden of chronic migraine (CM), it is challenging to identify the best prevention treatment. Based on the preclinical evidence about the different therapeutic targets of onabotulinumtoxinA (BT-A), acting on C-fibers, and anti-CGRP monoclonal antibodies (mAbs), acting on Aδ-fibers, the rationale of using alternative or combining therapies has been hypothesized. Until now, the association of BT-A and mAbs has been poorly investigated. This study evaluated whether mAbs are effective and safe in CM patients previously treated with BT-A, either as an alternative or add-on treatment. We enrolled 47 patients: according to the response to BT-A treatment, patients were defined as non-responder (NR) and partial-responder (PR). NR were shifted to mAbs. PR were randomly divided into those who added mAbs therapy (PR-P) and those who shifted treatment (PR-S), interrupting BT-A. Clinical variables were collected at baseline, after three and six months. Study results evidenced the efficacy of mAbs in improving clinical outcomes in CM patients, with a better response in the PR group. No statistically significant differences in clinical changes were observed between PR-P and PR-S groups. No safety concerns were raised in combined treatments. Preventive prophylaxis with mAbs is effective, even in difficult to treat CM patients. Further studies, with larger samples, are needed to highlight a potential additive effect of combined therapies.

Background: Bruxism is a jaw-muscle activity characterized by teeth grinding and clenching. While many of its negative consequences (e.g., jaw-muscle pain, tooth fractures) are of particular interest to dentists, new insights underline the need for physicians to be knowledgeable about bruxism. In order to facilitate transfer of knowledge across disciplines, our objective was to assess what top-ranking medical journals have published on bruxism. Besides, we tested the insights described there against current science regarding the definition, assessment, epidemiology, etiology, consequences, comorbidities, and management of bruxism. Results: In the past century, the four top-ranking medical journals have provided their readership with various bits and pieces of information on bruxism. While some of these insights have withstood the test of time, others are somewhat outdated. Further, the identified publications provide an incomplete picture of what physicians should know. The present article helps reduce this knowledge gap. Conclusion: The role of the physician with regard to bruxism focuses mainly on its assessment and management, while insight into risk factors and comorbid conditions of bruxism is essential to high-level patient care. It is hoped that this article will contribute to improve the long-needed interdisciplinary collaboration between physicians and dentists regarding the assessment and management of bruxing patients.

Background There is a growing awareness of constipation being a side effect of anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAbs). This study aims to assess constipation as a side effect and explore its potential role as a predictor of treatment response in chronic migraine (CM) patients treated with anti-CGRP mAbs. Methods We conducted a retrospective analysis of patients with CM treated with anti-CGRP mAbs between January 2019 and December 2022 at a single center. Data on patient demographics, migraine characteristics, and constipation were reviewed. Results Among 317 patients, 192 received erenumab, 94 received fremanezumab, and 31 received galcanezumab. Constipation was significantly more common with erenumab (51.5%) compared to fremanezumab (4.2%) and galcanezumab (12.9%). Among erenumab patients, 24.4% switched due to constipation, while 19.2% switched due to lack/loss of effectiveness. Patients who switched treatment experienced milder symptoms ( p < 0.0001) without compromising effectiveness, even when switching due to lack/loss of effectiveness ( p = 0.0068). Importantly, severe constipation rates were higher in non-responders ( p = 0.036). Conclusion Constipation is a notable side effect of anti-CGRP mAbs, particularly with erenumab in CM. Side effect monitoring is consequently crucial. Our findings suggest a potential link between poor treatment response and constipation, warranting further research into the underlying mechanisms.