Head trauma has been described as a precipitating event in Nummular Headache (NH). We aimed to describe the largest NH published series and compare characteristics between idiopathic and post-traumatic cases. Patients attended in a Headache Unit in a tertiary hospital (January 2008–January 2018). NH diagnosed according to International Classification of Headache Disorders (ICHD) criteria. We prospectively considered clinical and epidemiological data, comparing idiopathic cases with those precipitated by a cranial trauma. We included 225 patients (145 women, 80 men) with NH. Median latency between onset and diagnosis was 10 months (IQR: 5–24). Symptomatic treatment was used in 190 patients (84.4%) among which 142 (74.7%) experienced response to it. Preventive treatment was necessary in 127 patients (51.4%), among which 95 (74.8%) achieved response. 29 patients (23 women, 6 men) described a head trauma related to beginning of pain. When comparing groups with or without previous trauma, age of onset was higher among post-traumatic patients (59.9 ± 17.4 vs 48.1 ± 18 years, p: 0.001). Allodynia upon palpation was encountered more frequently in trauma triggered painful areas (53.3% vs. 32.7%, p: 0.02). No other clinical characteristics differences were observed. Cranial trauma is not a rare trigger of NH. Patients with post-traumatic forms are older and the presence of allodynia is more frequent.

Nummular headache is a primary headache characterised by superficial, coin-shaped pain. Superficial sensory fibre dysfunction might be involved in its pathophysiology. Considering the mechanism of action of onabotulinumtoxinA, it could be a reasonable option in treatment of nummular headache. The aim of the study was to evaluate the efficacy and tolerability of onabotulinumtoxinA in a series of nummular headache patients. This was an observational, prospective, non-randomized and open-label study. Nummular headache patients with at least 10 headache days in three preceding months were included. They were administered 25 units of onabotulinumtoxinA. The primary endpoint was the decrease of headache days per month, evaluated between weeks 20 to 24, compared with baseline. The secondary endpoints included reduction of intense headache days and acute treatment days evaluated between weeks 20–24 and weeks 8–12, compared with baseline. The 30%, 50% and 75% responder rates were determined, and tolerability described. We included 53 patients, 67.9% females, with a median age of 54 years. Preventive treatment had been used previously in 60.4% of patients. The median diameter of the nummular headache was 5 cm. At baseline, the number of headache days per month was 24.5 (7.3); the number of intense headache days was 12.5 (10.1), and the number of acute treatment days was 12.8 (7.8). After onabotulinumtoxinA, the mean number of headache days per month decreased to 6.9 (9.3) between weeks 20 and 24 (p < 0.001). Secondary endpoints concerning intense headache days per month and acute treatment days per month were also statistically significant (p < 0.001). The 50% responder rate, evaluated between weeks 20 and 24, was 77.4% and the 75% responder rate was 52.8%. Concerning tolerability, 26 patients (49.1%) experienced an adverse event (AE), the commonest being injection-site pain in 12 cases (22.6%). There were no moderate or severe AEs. It was found that after injecting onabotulinumtoxinA, the number of headache days per month was reduced in nummular headache patients. The number of intense headache days per month and acute treatment days were also lowered. No serious adverse events occurred during treatment.

Nummular headache (NH) is a primary headache characterized by superficial coin-shaped pain. NUMITOR (NCT 05475769) is an observational study evaluating the responder rate of preventive drugs in NH patients. The treatment response was assessed between weeks 8 and 12 compared with the baseline. Patients were included between February 2002 and October 2022. Demographic and clinical variables were assessed; treatment response was estimated by 50%, 30%, and 75% responder rates and treatment discontinuation due to inadequate tolerability. A total of 183 out of 282 patients fulfilled eligibility criteria and completed the study. Patients were aged 49.5 (standard deviation (SD): 16.8) years, and 60.7% were female. NH phenotype was a parietal circular pain of four centimeters’ diameter, moderate intensity, and oppressive quality. At baseline, patients had 25 (interquartile range) pain days per month. Preventive treatment was used by 114 (62.3%) patients. The highest 50% and 75% responder rates corresponded to onabotulinumtoxinA (62.5%, 47.5%), followed by gabapentin (43.7%, 35.2%). Oral preventive drugs were not tolerated by 12.9–25%. The present study provides class IV evidence of the effectiveness of oral preventive drugs and onabotulinumtoxinA in the treatment of primary NH. OnabotulinumtoxinA was the most effective and best-tolerated drug, positioning it as first-line treatment of NH.

Objective: To evaluate clinical characteristics, effectiveness, and tolerability of preventive anti- calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) in the elderly. Anti-CGRP mAbs have demonstrated efficacy and safety in patients with migraine although there is limited information regarding the elderly. Design: We performed a multicenter case-control study of cases (patients over 65 years old) and controls (sex-matched patients under 55 years old) with migraine receiving anti-CGRP mAbs. Methods: We included the demographic characteristics, effectiveness—reduction in the number of monthly headache days (MHD) and monthly migraine days (MMD), 30%, 50%, and 75% responder rates—and treatment emergent adverse events (TEAEs). The primary endpoint was the 50% response rate regarding MHD at weeks 20–24; exploratory 50% response predictors in the elderly were evaluated. Results: In total, 228 patients were included: 114 cases , 114 controls-. Among cases 84.2% (96/114) were women, 79.8% (91/114) CM; mean age of cases 70.1 years old (range: 66–86); mean age of controls was 42.9 years old(range: 38–49). Cases had a higher percentage of vascular risk factors (P < .05),older age of onset (P < .001) and more reported prior preventive treatments (P < .001). Regarding effectiveness in cases, 50% response rate was achieved by 57.5% (42/73) at 20–24 weeks, with lower reduction in the MHD at 8–12 weeks (5 [7.2], 8 [9.1]; P = .001) and a higher reduction in MMD at 20–24 weeks (10.7 [9.1], 9.2 [7.7]; P = .04) compared to the control group. The percentage of TEAEs was similar in the 2 groups. Diagnosis of episodic migraine (EM) (P = .03) and lower number of MHD at baseline (P = .001) were associated with a 50% response in the elderly in univariate analysis. Conclusions: Our study provides real world evidence of effectiveness and safety of anti-CGRP mAbs for migraine in patients without upper age-limit and possible predictors of anti-CGRP response in the elderly.

Background: Preclinical evidence supports the immunoregulatory role of calcitonin gene-related peptide (CGRP) in migraine pathophysiology. The increasing use of anti-CGRP therapies in patients with migraine and other comorbidities raises the question whether the potential use of anti-CGRP monoclonal antibodies (CGRP-mAbs) therapies in combination with other immunological therapies is effective and safe. Methods: This multicenter study included patients with migraine receiving CGRP-mAbs combined with immunosuppressive and immunomodulatory treatments. Clinical and demographic data, treatment history, laboratory markers and treatment-emergent adverse events (TEAEs) were analyzed. Effectiveness outcomes included the change in monthly migraine days (MMD) and monthly headache days (MHD) at 3, 6, 9 and 12 months, alongside the > 50% response rate. Moreover, autoimmune disease progression was also evaluated. We explored differences between patients with and without autoimmune disease activation. Results: Among 89 patients, there were 80 (90%) females with a mean age of 50 years (SD: 11), who had a high prevalence of psychiatric comorbidities (anxiety 44%, depression 49%) and medication overuse (68%). Patients receiving immunological treatments experienced significant reductions in MMD and MHD, with MMD decreasing from 16 (SD: 7) at baseline to 9 (SD: 8) at 6 months, and MHD dropping from 23 (SD: 8) to 17 (SD: 11). A 50% response in MMD was achieved by 46% at 6 months. TEAEs were reported in 28%, most commonly constipation (16%) and dizziness (9%). Conclusions: CGRP-mAbs therapies combined with immunological treatments appear effective and safe in patients with autoimmune diseases. Larger prospective studies are necessary to confirm these findings and optimize management strategies.