PACAP-38 and sex hormones in women with migraine: exploratory analysis of a cross-sectional, matched cohort study.

BACKGROUND: Endogeneous and exogeneous sex hormones can impact the frequency and severity of migraine attacks, but the underlying mechanisms are poorly understood. In this study, we investigate the relationship between female sex hormones and Pituitary Adenylate Cyclase-Activating Polypeptide-38 (PACAP-38) concentrations in plasma of women with migraine and healthy controls, aiming to elucidate potential hormonal influences on PACAP dynamics and their relevance to migraine pathophysiology. METHODS: This analysis is part of a cross-sectional, matched-cohort study. We recruited two groups of women with episodic migraine: one with a regular menstrual cycle (M-RMC) and another undergoing combined oral contraceptive treatment (M-COC). Additionally, we included corresponding age-matched control groups without migraine for both categories (C-RMC and C-COC). For participants with a RMC, the study visits were scheduled during the perimenstrual period (menstrual cycle day 2 ± 2) and periovulatory period (day 13 ± 2). Participants using COC were examined at day 4 ± 2 of the hormone-free interval and between day 7-14 of the hormone intake phase. During these visits, PACAP-38 concentrations in plasma were measured using a commercial Enzyme-linked-immunosorbent assay (ELISA) kit. RESULTS: The study included 120 women, with 30 participants in each group. Women with migraine and a RMC had significantly higher PACAP-38 plasma concentrations compared to healthy controls at both study visits [day 2 ± 2: M-RMC: 2547.41 pg/ml (IQR 814.27 - 4473.48) vs. C-RMC: 1129.49 pg/ml (IQR 257.34 - 2684.88), p = 0.025; day 13 ± 2: M-RMC: 3098.89 pg/ml (IQR 1186.29 - 4379.47) vs. C-RMC: 1626.89 (IQR 383.83 - 3038.36), p = 0.028]. In contrast, PACAP-38 levels were comparable between migraine and control groups receiving COC. Women with migraine and a RMC exhibited higher PACAP-38 concentrations during menstruation compared to those using COC during the hormone-free interval. CONCLUSION: Systemic PACAP-38 concentrations in women vary based on the presence of migraine diagnosis and their hormonal status.

Alice in Wonderland Syndrome (AIWS): prevalence and characteristics in adults with migraine.

OBJECTIVE: Alice in Wonderland Syndrome (AIWS) is a sensory disorder characterized by a distorted somatosensory and/or visual perception. Additionally, distortion of time perception and symptoms of derealization/depersonalization may occur. AIWS is frequently associated with migraine. However, its prevalence, and clinical characteristics remain poorly understood. Here, we investigated the prevalence and features of AIWS in individuals with migraine. We hypothesized AIWS is more frequent in migraine patients with aura than in those without aura. METHODS: This was a prospective cross-sectional cohort study, conducted at a tertiary headache center. Participants with migraine filled out questionnaires, providing details on demographics, headache, AIWS characteristics and the occurrence of transient visual phenomena such as fragmented vision. RESULTS: Of 808 migraine patients, 133 individuals (16.5%, mean age 44.4 ± 13.3 years, 87% women) reported AIWS symptoms throughout their lives. Micro- and/or telopsia (72.9%) were most frequent, followed by micro- and/or macrosomatognosia (49.6%), and macro- and/or pelopsia (38.3%), lasting on average half an hour. AIWS symptoms occurred in association with headache in 65.1% of individuals, and 53.7% had their first AIWS episode at the age of 18 years or earlier. Migraine patients with aura were more likely to report AIWS symptoms than those without aura (19.5% vs. 14.1%, p = 0.04). Participants with AIWS reported a higher incidence of 17 out of the 22 investigated visual phenomena. CONCLUSION: AIWS symptoms appear to be a common lifetime phenomenon in migraine patients. The correlation and clinical parallels between AIWS and migraine aura could indicate shared underlying pathomechanisms.

Near-death experiences are associated with rapid eye movement (REM) sleep intrusions in migraine patients, independent of migraine aura.

BACKGROUND AND PURPOSE: Migraine aura, near-death experiences (NDEs), and rapid eye movement (REM) sleep intrusions might share common mechanisms. Here, we investigated the prevalence of NDEs and REM sleep intrusions in people with migraine. We hypothesized that NDEs and REM sleep intrusions are more prevalent in migraine patients with aura than in those without. METHODS: We conducted a prospective cross-sectional cohort study at a tertiary headache center, based on a prespecified sample size (n = 808). Migraine patients completed a series of questionnaires, including questions about demographic and headache characteristics, the 16-item Greyson NDE scale, four questions about REM sleep intrusions, and the Depression, Anxiety, and Stress Scale 21 (DASS-21). RESULTS: Of 808 migraine patients (mean age 44.4 ± 13.3 years, 87.0% women), 353 (43.7%) had a current or previous history of migraine aura. Prevalence of NDE was 2.7% and not different in patients with and without aura (2.8% vs. 2.6%; p > 0.999). REM sleep intrusions were reported by 5.4% of participants and in a similar proportion of patients with and without aura (6.3% vs. 4.9%; p = 0.43). However, participants with REM sleep intrusions had had an NDE more often than participants without REM sleep intrusions (n = 5/44, 11.4% vs. n = 17/754, 2.2%; p = 0.005). Higher DASS-21 scores were associated with REM sleep intrusions (p < 0.001). CONCLUSIONS: In this tertiary center cohort study, the prevalence of NDE and REM sleep intrusions was not influenced by migraine aura status. However, we identified an association between NDE and REM sleep intrusions, which corroborates the notion that they might share pathophysiological mechanisms.

Clinical evaluation of super-responders vs. non-responders to CGRP(-receptor) monoclonal antibodies: a real-world experience.

BACKGROUND: Clinical trials and real-world studies revealed a spectrum of response to CGRP(-receptor) monoclonal antibodies (mAbs) in migraine prophylaxis, ranging from no effect at all to total migraine freedom. In this study, we aimed to compare clinical characteristics between super-responders (SR) and non-responders (NR) to CGRP(-receptor) mAbs. METHODS: We performed a retrospective cohort study at the Headache Center, Charité - Universitätsmedizin Berlin. The definition of super-response was a ≥ 75% reduction in monthly headache days (MHD) in the third month after treatment initiation compared to the month prior to treatment begin (baseline). Non-response was defined as ≤ 25% reduction in MHD after three months of treatment with a CGRP-receptor mAb and subsequent three months of treatment with CGRP mAb, or vice versa. We collected demographic data, migraine disease characteristics, migraine symptoms during the attacks in both study groups (SR/NR) as well as the general medical history. SR and NR were compared using Chi-square test for categorical variables, and t-test for continuous variables. RESULTS: Between November 2018 and June 2022, n = 260 patients with migraine received preventive treatment with CGRP(-receptor) mAbs and provided complete headache documentation for the baseline phase and the third treatment month. Among those, we identified n = 29 SR (11%) and n = 26 NR (10%). SR reported more often especially vomiting (SR n = 12/25, 48% vs. NR n = 4/22, 18%; p = 0.031) and typical migraine characteristics such as unilateral localization, pulsating character, photophobia and nausea. A subjective good response to triptans was significantly higher in SR (n = 26/29, 90%) than in NR (n = 15/25, 60%, p = 0.010). NR suffered more frequently from chronic migraine (NR n = 24/26, 92% vs. SR n = 15/29, 52%; p = 0.001), medication overuse headache (NR n = 14/24, 58% versus SR n = 8/29, 28%; p = 0.024), and concomitant depression (NR n = 17/26, 65% vs. SR n = 8/29, 28%; p = 0.005). CONCLUSION: Several clinical parameters differ between SR and NR to prophylactic CGRP(-R) mAbs. A thorough clinical evaluation prior to treatment initiation might help to achieve a more personalized management in patients with migraine.

Migraine and Hormonal Contraception in Gynecological Outpatient Care-Cross-Sectional Study among Practicing Gynecologists in Germany.

Hormonal contraception (HC) can influence the migraine burden and should be considered in the comprehensive management of women with migraine. In this study, we aim to investigate the influence of migraine and migraine aura on the prescribing behavior of combined oral contraception (COC) and progestogen monotherapy (PM) in gynecological outpatient care. From October 2021 to March 2022, we performed an observational, cross-sectional study using a self-administered online-based survey. The questionnaire was distributed by mail and e-mail among 11,834 practicing gynecologists in Germany using the publicly available contact information. A total of 851 gynecologists responded to the questionnaire, of whom 12% never prescribe COC in the presence of migraine. Further 75% prescribe COC depending on the presence of limiting factors such as cardiovascular risk factors and comorbidities. When deciding to start PM, migraine appears to be less relevant, as 82% prescribe PM without restrictions. In the presence of aura, 90% of gynecologists do not prescribe COC at all, while PM is prescribed in 53% without restrictions. Almost all gynecologists reported to be actively involved in migraine therapy by having already initiated (80%), discontinued (96%), or changed (99%) HC due to migraine. Our results reveal that participating gynecologists actively consider migraine and migraine aura before and while prescribing HC. Gynecologists appear cautious in prescribing HC in patients with migraine aura.