Efficacy of Nutūl-i-Ḥār (Hot Irrigation), a Polyherbal Unani Formulation, in the Treatment of Shaqīqa-i-Muzmin (Chronic Migraine): An Open Single-Arm Exploratory Clinical Trial

Shaqīqa-i-Muzmin (chronic migraine) is a type of migraine that is usually caused by cold humours (bārid akhlāṭ), specifically by phlegm (balgham) and to lesser extent by black bile (sauda). The aim of this study was to evaluate the effect of Nutul-i-Ḥār (hot irrigation) in the treatment of chronic migraine. Nutul (irrigation) therapy is widely and successfully used in diseases of head as described in Unānī system of medicine. This open, single-arm, exploratory clinical study was conducted in 30 patients of chronic migraine selected by convenient sampling method. One litre decoction prepared with 12 g each of Astragalus hamosus L. (Iklilul malik), Matricaria chamomilla L. (Babuna), Artemisia absinthium L. (Afsanteen), Origanum vulgare L. (Marznjosh) and Trigonella foenum graecum L. (Hulba) was poured over painful side of head for 45 minutes on every alternate day for a period of 30 days (15 sittings). The patients, thereafter, were followed untill 90th day of the study for various outcome measures comprising headache intensity, headache frequency, Migraine Disability Assessment Scale (MIDAS), and rescue medication. The reduction in headache frequency, MIDAS score and use of rescue medication was significant (p < 0.001) after the treatment. Reduction in headache intensity at 30th day, 60th day and 90th day was significant as compared with baseline values (p < 0.001) but not statistically significant at 90th day with respect to 60th day (p > 0.05). Statistical analysis was done using parametric (paired t-test) and non-parametric tests (Wilcoxan sign ranked test, Freidman with Dunn’s multiple comparison tests). Hot irrigation with medicated decoction was found effective in the treatment of chronic migraine.

Headache provocation by nitric oxide in men who have never experienced a headache

Introduction In the general population 4% have never experienced a headache. Freedom from headache could be due to distinctive protective mechanisms or a lack of environmental risk factors for headache. Isosorbide-5-mononitrate is an organic nitrate which in the body is metabolised to nitric oxide. The nitric oxide pathway plays a crucial role in the primary headaches. We hypothesized that people who are free from headache are protected by distinctive mechanisms in the nitric oxide pathway. Methods We performed an observer blinded case-control study using nitric oxide to provoke a headache. 32 headache free male participants and 26 randomly selected male controls received 60 mg Isosorbide-5-mononitrate orally on the study day. Participants fill out a headache diary with headache intensity and characteristics until 12 hours after administration of Isosorbide-5-mononitrate. Primary endpoint were areas under the curve of headache intensity score. Results All 58 participants completed the study. There was no significant difference in headache incidence, headache intensity score or migraine-like attack between headache free participants and controls. Conclusion We show that men who have never experienced a headache develop a headache when provoked with Isosorbide-5-mononitrate. This indicates that freedom from headache in men is not related to the nitric oxide pathway which is involved in the primary headache disorders.

Comparing Perimenstrual and Nonperimenstrual Migraine Attacks Using an e-Diary

BackgroundEndogenous and exogenous female sex hormones are considered important contributors to migraine pathophysiology. Previous studies have cautiously suggested that perimenstrual migraine attacks have a longer duration and are associated with higher disability compared to non-perimenstrual attacks, but they showed conflicting results on acute therapy efficacy, pain intensity, and associated symptoms.ObjectivesTo compare perimenstrual and non-perimenstrual migraine attack characteristics and assess premenstrual syndrome (PMS) in women with migraine.MethodsWomen with migraine were invited to complete a headache E-diary. Characteristics of perimenstrual attacks and non-perimenstrual attacks were compared. The primary outcome was attack duration. Secondary outcomes were headache intensity, accompanying symptoms, acute medication intake and pain coping. Mixed effects models were used to account for multiple attacks within patients. PMS was assessed in those without hormonal contraceptives. Subgroup analyses were performed for women with menstrually related migraine (MRM) and non-menstrually related migraine (non-MRM), and women with a natural menstrual cycle and women using hormonal contraceptives.ResultsA representative group of n=500 participants completed the E-diary for at least one month. Perimenstrual migraine attacks (n=998) compared with non-perimenstrual attacks (n=4097) were associated with longer duration (20.0 vs 16.1 hours, 95%CI [0.2-0.4]), higher recurrence risk (OR 2.4 [2.0-2.9]), increased triptan intake (OR 1.2 [1.1-1.4]), higher headache intensity (OR 1.4 [1.2-1.7]), less pain coping (mean difference -0.2 [-0.3- -0.1]), more pronounced photophobia (OR 1.3 [1.2-1.4]) and phonophobia (OR 1.2 [1.1-1.4]) and less aura (OR 0.8 [0.6-1.0]). In total 396/500 women completed the diary for ≥3 consecutive menstrual cycles, of whom 56% (221/396) fulfilled MRM criteria. Differences in attack characteristics became more pronounced when focusing on women with MRM and women using hormonal contraceptives. Prevalence of PMS was not different for women with MRM compared to non-MRM (11% vs. 15%).DiscussionThe longer duration of perimenstrual migraine attacks in women (with MRM) is associated with higher recurrence risk and increased triptan use. This may increase the risk of medication overuse and emphasizes the need to develop female-specific prophylactic treatment.

Pooled retrospective analysis of 70 mg erenumab in episodic and chronic migraine: a two tertiary headache centers experience during clinical practice

Erenumab is a monoclonal antibody, targeted against the calcitonin gene-related peptide (CGRP) receptor. Clinical studies have demonstrated prophylactic efficacy in both episodic (EM) and chronic migraine (CM). The aim of the present study is to evaluate the efficacy of treatment in tertiary headache centers under real-life conditions. In a retrospective analysis, the period of 3 months before and after initiation of erenumab therapy was compared. Relevant parameters (headache days, headache intensity, headache duration, acute medication, previous prophylaxis treatments) were collected from medical charts of all migraine patients (N = 82) who started treatment with erenumab between November 1st 2018 and May 1st 2019 at two tertiary headache centers in Germany. The sample included 68 female (82.9%) and 14 male patients aged between 22 and 78 years (mean 51.1 years, SD 10.5 years). Of these patients, 57.3% met the criteria for CM and 56.9% overused acute medication. Under therapy with erenumab, a significant reduction of headache days was observed from the first month on. The effect was most pronounced in the third month with a decrease in monthly headache days from 16.6 to 11.6 days (p < 0.001). There was also a significant reduction in reported headache intensity (p = 0.004) and average duration of headache attacks (p = 0.016). The 50% responder rate in patients with CM was lower in the first month compared to EM but then increased similarly to EM. Patients with medication overuse (MO) also responded to the therapy. There was a reduction in medication overuse from 57% at baseline to 29% after therapy (p = 0.011). Overall, a positive result of treatment with erenumab can be shown in a highly selected sample with severely affected migraine patients and a refractory course prior to treatment. This re-confirms the clinical trial data also for this highly selected group.

The Effect of KATP Channel Blocker Glibenclamide on CGRP-Induced Headache and Hemodynamic in Healthy Volunteers

BackgroundCalcitonin gene-related peptide (CGRP) dilates cranial arteries and triggers headache. The CGRP signaling pathway is partly dependent on activation of ATP-sensitive potassium (KATP) channels. Here, we investigated the effect of the KATP channel blocker glibenclamide on CGRP-induced headache and vascular changes in healthy volunteers.MethodsIn a randomized, double-blind, placebo-controlled, cross-over study, 20 healthy volunteers aged 18–27 years were randomly allocated to receive an intravenous infusion of 1.5 μg/min CGRP after oral pretreatment with glibenclamide (glibenclamide-CGRP day) or placebo (placebo-CGRP day). The primary endpoints were the difference in incidence of headache and the difference in area under the curve (AUC) for headache intensity scores (0–14 h) between glibenclamide and placebo. The secondary endpoints were the difference in AUC for middle cerebral artery blood flow velocity (VMCA), superficial temporal artery (STA) and radial artery (RA) diameter, facial flushing, heart rate (HR) and mean arterial blood pressure (MAP) (0–4 h) between glibenclamide and placebo.ResultsWe found no significant difference in the incidence of headache between glibenclamide-CGRP day (14/20, 70%) and placebo-CGRP day (19/20, 95%) (P = 0.06). The AUC for headache intensity, VMCA, STA, RA, facial skin blood flow, HR, and MAP did not differ between glibenclamide-CGRP day compared to placebo-CGRP day (P &gt; 0.05).ConclusionPretreatment with a non-selective KATP channel inhibitor glibenclamide did not attenuate CGRP-induced headache and hemodynamic changes in healthy volunteers. We suggest that CGRP-induced responses could be mediated via activation of specific isoforms of sulfonylurea receptor subunits of KATP channel.

Effectiveness of the Treatment of Rhinogenic Headache Caused by Intranasal Contact

Objectives: The aim of the study is to evaluate the effectiveness of the surgical and nonsurgical treatment of headache caused by contact points (CPs) between the nasal septum and inferior or middle turbinate. Methods: The research was designed as a prospective clinical case-series study. The patients with CP headaches were offered to choose between 2 treatment options, surgery and medical treatment. Two groups of surgically treated patients (surgery groups 1 and 2, depending on whether there is a contact between nasal septum and inferior turbinate or middle turbinate) were evaluated and compared for headache intensity and frequency. Headache intensity was measured using a visual analog scale value from 0 to 10; the frequency of headache was expressed as the number of days during 1 month with a headache (before surgery, 1 month, and 6 months after surgery). A comparison was also made between surgically and nonsurgically treated patients. Results: We found more intensive and frequent headache in patients who had CP between the nasal septum and the middle turbinate ( P = .038 and P = .003, respectively). A significant reduction in headache intensity and frequency was found in both groups of surgically treated patients 6 months after surgery; however, this reduction was more significant in patients with mucosal contact between nasal septum and middle turbinate. The nonsurgical treatment made a significant reduction of headache intensity and frequency at 1-month follow-up ( P = .012 and P = .031, respectively), but not at 6-month follow-up ( P = .114 and P = .088, respectively). Conclusion: Surgery gave a statistically significant reduction in the intensity and frequency of headache, which was assessed 6 months after surgery. Surgery was found as superior to nonsurgical treatment in the therapy of CP headache.

The impact of COVID-19 pandemic on headache symptoms and drug withdrawal among patients with medication overuse headache: a cross-sectional study

Background Coronavirus disease 2019 (COVID-19) bring about a range of psychological distress and symptom deterioration to headache patients especially to some migraineurs. Compared to migraineurs or normal control, medication overuse headache (MOH) patients are more likely to experience a worse psychological distress and poorer outcome in non-COVID-19 time. However, in COVID-19 pandemic, whether MOH patients would have greater physical and mental symptom deterioration or worse relief of headache symptoms and medications overuse remained unclear. We aim to investigate the impact of COVID-19 on MOH patients to guide for a better management in this study. Methods We enrolled MOH patients who were diagnosed and treated at headache clinic of West China Hospital. Information of the pre-pandemic 3 months period and COVID-19 pandemic period was collected. Univariate and multivariate logistic regression were performed to identify independent factors associated with changes in headache symptoms and drug withdrawal. Results Seventy-eight MOH patients were enrolled into the study ultimately. In comparison to pre-pandemic period, fewer MOH patients reported decreased headache days, intensity and days with acute medications per month during the pandemic. Available access to regular prophylactic medications was significantly associated with a reduction of at least 50% in headache days and decrease in headache intensity per month with respective odds ratios of 39.19 (95% CI 3.75–409.15, P = 0.002) and 10.13 (95% CI 2.33–44.12, P = 0.002). Following abrupt withdrawal and high educational level were both significant factors in decreasing headache intensity. Male sex was significantly associated with decrease in days with acute medication per month during the pandemic (odds ratios 4.78, 95%CI 1.44–15.87, P = 0.011). Conclusions Our findings reflect that MOH patients experienced a worse relief of headache symptoms and drug withdrawal during the pandemic. Available access to regular prophylactic medications was the significant independent factor for improvement of headache symptoms. Male sex was significantly associated with decreased days with acute medications per month.

Migraine during COVID-19: Data from Second Wave Pandemic in an Italian Cohort

Objectives: The study aims to assess the impact of the second COVID-19 pandemic wave on migraine characteristics. Methods: This is an observational cross-sectional study conducted on migraine patients previously interviewed during the first Italian pandemic outbreak. A second structured telephone interview was conducted between 20 November 2020 and 18 January 2021. We compared migraine characteristics among T0 (before pandemic), T1 (during the first pandemic phase), and T2 (during the second pandemic phase). Results: Among the 433 patients interviewed during the first pandemic phase, 304 cases were finally considered. One hundred forty-eight patients had a control visit between March 2020 and December 2020, 120 had an in-person visit, 14 by phone, the remainder used telemedicine software provided by the hospital. Frequency of headache, number of symptomatic drugs and headache intensity worsened during T2, compared to T0 and T1, especially in episodic migraine. Headache intensity increased relating to the negative emotional impact of the pandemic. Migraine management during the pandemic did not influence the clinical outcome. Conclusion: The prolongation of the pandemic seems to have a negative impact on migraine evolution. The arousal and negative psychological behavior toward the COVID-19 outbreak seem to worsen migraine.

Effect of Adrenomedullin on Migraine-like Attacks in Patients With Migraine: A Randomized Crossover Study

ObjectiveTo determine whether the intravenous infusion of adrenomedullin, a potent vasodilator belonging to calcitonin family of peptides, provokes attacks of migraine in patients.MethodsTwenty migraine without aura patients participated in a placebo-controlled and double-blinded clinical study. In a randomized and crossover design the patients received an intravenous infusion of human adrenomedullin (19.9 picomole/kg/min) or placebo (saline) administrated via an automated intravenous pump (20 minutes). The patients participated in two study days with washout period of minimum of seven days. The primary outcome of the study was predefined as a difference in migraine incidence (0–12 h) and the secondary outcome were the headache intensity score’s area under curve (AUC0-12 h) and the (AUC 0-90 min) for MAP, flushing and HR.ResultsEleven migraine without aura patients (55%) fulfilled migraine attacks criteria after adrenomedullin infusion in comparison to only three patients reported attack (15%) after placebo (P= 0.039). We found that patients reported in a period of (0-12 hours) stronger headache intensity after adrenomedullin in comparison to placebo infusion (P= 0.035). AUC0-90 min for HR and, flushing (P < 0.05) were significant and MAP (P = 0.502) remain unchanged. Common adverse events reported were facial flushing, heat sensation and palpitation (P <0.001)ConclusionOur data implicate adrenomedullin in migraine pathogenesis. This suggests that adrenomedullin and/or its receptors are novel therapeutic targets for the treatment of migraine. However, we cannot discount for the possibility that adrenomedullin may be acting through the canonical CGRP receptor.