REVIEW | doi:10.20944/preprints201706.0067.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: Transition Medicine; Pediatric migraine; Pediatric; Migraine; Migraine in young adults
Online: 14 June 2017 (09:26:13 CEST)
Migraine is a common condition that affects children as they develop into adults. Transition of care from pediatric to adult care has becoming an increasingly popular topic in the medical literature. It has been suggested that discussions between patients, their families and providers should be initiated as early as age 13. Patients who are un or underprepared have poorer outcomes due to increased morbidity and worsening of their medical condition. Many children continue to have migraine into adulthood and if efforts are taken to ensure patients receive appropriate transfer of care, the results can significantly decrease the economic burden of this disease.
HYPOTHESIS | doi:10.20944/preprints202009.0588.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: electromagnetic hypersensitivity; multiple chemical sensitivity; migraine; TRPA1
Online: 24 September 2020 (18:22:45 CEST)
According to the French Agency for Food, Environmental and Occupational Health & Safety, electromagnetic hypersensitivity affects more than 3 million people in France, and headaches are a very frequent cause of complaint in electrohypersensitive patients, to the point of dominating the clinical picture. These headaches share characteristics with migraine pathology, and clinical improvement with anti-migraine therapy has led us to consider that the headache in the electrohypersensitive patient may be a variant of the migraine disease mediated by the TRPA1 receptor, which if confirmed, would offer effective therapeutic possibilities to relieve the electrohypersensitive patient.
REVIEW | doi:10.20944/preprints202111.0064.v1
Subject: Medicine & Pharmacology, Other Keywords: primary headache; migraine; trigeminal system; neuropeptides; neurogenic inflammation; animal model; inflammatory soup; dura mater; immune system; migraine treatment
Online: 3 November 2021 (08:30:58 CET)
Migraine is a primary headache disorder characterized by unilateral throbbing, pulsing headache, which lasts for hours to days, and the pain can interfere with daily activities. It exhibits various symptoms, such as nausea, vomiting, sensitivity to light, sound, and odors and physical activity consistently contributes to worsening pain. Despite the intensive research, little is still known about the pathomechanism of migraine. It is widely accepted that migraine involves activation and sensitization of the trigeminovascular system. It leads to the release of several pro-inflammatory neuropeptides and neurotransmitters and causes a cascade of inflammatory tissue responses including vasodilation, plasma extravasation secondary to capillary leakage, edema, and mast cell degranulation. Convincing evidence obtained in rodent models suggests that neurogenic inflammation is assumed to contribute to the development of a migraine attack. Chemical stimulation of the dura mater triggers activation and sensitization of the trigeminal system and causes numerous molecular and behavioral changes; therefore, this is a relevant animal model of acute migraine. This review article discusses the emerging evidence supporting the involvement of neurogenic inflammation and neuropeptides in the pathophysiology of migraine, presenting the most recent advances in preclinical research and the novel therapeutic approaches to the disease.
ARTICLE | doi:10.20944/preprints202108.0162.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: vertigo; migraine; cytokines; inflammation; vestibular disorders; hearing loss
Online: 6 August 2021 (12:29:43 CEST)
Background: Meniere disease (MD) is an inner ear disorder associated with comorbidities such as autoimmune diseases or migraine. This study describes clinical and cytokine profile in MD according to the age of onset of the condition. Methods: A cross-sectional study including 83 MD patients: 44 with early onset MD (EOMD, <35 years old), and 39 with late onset MD (LOMD, > 50 years old), 64 patients with migraine and 55 controls was carried out. Clinical variables and cytokines levels of CCL3, CCL4, CCL18, CCL22, CXCL1 and IL-1β were compared among the different groups. Results: CCL18 levels were higher in patients with migraine or MD than in controls. Elevated levels of IL-1β were observed in 11.4% EOMD and in 10.3% LOMD patients and these levels were not dependent on the age of individuals. EOMD had a longer duration of the disease (p=0.004) and a higher prevalence of migraine than LOMD (p=0.045). Conclusions: Patients with EOMD have a higher prevalence of migraine than LOMD, but migraine is not associated with any cytokine profile in patients with MD. The levels of CCL18, CCL3 and CXCL4 were different between patients with MD or migraine and controls.
ARTICLE | doi:10.20944/preprints201802.0056.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: cervical spondylosis; migraine; retrospective cohort study; population-based
Online: 7 February 2018 (06:40:48 CET)
Background: Few studies have investigated the longitudinal association between cervical spondylosis (CS) and migraine by using a nationwide population-based database. Methods: We conducted a retrospective cohort study from 2000 to 2011 identifying 27,930 cases of cervical spondylosis and 111,720 control subjects (those without cervical spondylosis) from a single database. The subjects were frequency-matched on the basis of sex, age, and diagnosis date. The non- cervical spondylosis cohort was four times the size of the cervical spondylosis cohort. To quantify the effects of cervical spondylosis on the risk of migraine, univariate and multivariate Cox proportional hazard regression analyses were used to calculate the hazard ratio (HR) and 95% confidence interval (CI). Results: After a 10-year follow-up controlling for potential confounding factors, overall migraine incidence was higher in the cervical spondylosis cohort than in the non- cervical spondylosis cohort (5.16 and 2.09 per 1,000 people per year, respectively; crude hazard ratio = 2.48, 95% confidence interval = 2.28–2.69) with an adjusted hazard ratio of 2.03 (95% confidence interval = 1.86–2.22) after accounting for sex, age, comorbidities, and medication. Individuals with myelopathy in the cervical spondylosis cohort had a 2.19 times (95% confidence interval = 1.80–2.66) higher incidence of migraine compared than did those in the non- cervical spondylosis cohort. Conclusion: Individuals with cervical spondylosis exhibited a higher risk of migraine than those without cervical spondylosis. The migraine incidence rate was even higher among individuals with cervical spondylotic myelopathy.
ARTICLE | doi:10.20944/preprints202210.0486.v1
Subject: Life Sciences, Immunology Keywords: Migraine; systemic inflmmation; serial systemic immune inflammatory indices; aura
Online: 31 October 2022 (11:17:24 CET)
Background: Migraine is the commonest complex neurological disorder affecting over a billion people worldwide. Neuroinflammation has long been considered to play an important role in the pathophysiology of migraine. The main aim of this single-centre, proof of concept, retrospective study was to determine the possible clinical utility of systemic immune-inflammatory response in migraine with and without aura in a hospitalized cohort. We measured the role of universally available serial white blood cell counts to calculate the serial systemic immune-inflammatory indices (SSIIi) and the potential association between aura and SSIIi changes in a cohort of migraine patients admitted to tertiary care center in Melbourne Australia.Main body: We retrospectively assessed patients' medical records presenting to Western Health with migraine over an 18 month period. Patients were classified as either having migraine with aura (MA) or without aura (MO) based on ICHD-3 criteria. Baseline demographics and brain imaging findings in each group were evaluated. Patients with two sets of white blood cell counts during the admission were included in the analysis. SSIIi were calculated as, neutrophil counts x platelet counts / lymphocyte counts. Correlation between SSIIi and MA and MO were assessed using SPSS27.Conclusion: SSIIi were elevated in MA and MO followed by a downward trend in both groups, with MA being statistically significant. This proof-of-concept study suggests the potential role of systemic inflammation in pathobiology of migraine. SSIIi appear to show clinical utility. Further comprehensive ,controlled , multicenter studies are required to clarify the exact role of systemic inflammatory response and the clinical utility of SSIIi in a subset of migraine in the Emergency department setting.
ARTICLE | doi:10.20944/preprints202108.0376.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: Migraine; Headache; Irritable Bowel Syndrome; Chronic Pain; Saudi Arabia
Online: 18 August 2021 (11:21:40 CEST)
Migraine is a primary headache disorder with a prevalence of 11.6% globally and 27% in Saudi Arabia. Irritable bowel syndrome has a prevalence of 9.2% worldwide. The prevalence of IBS has not been established nationally. However, provincial studies for both migraine and IBS have been conducted across the nation. There is a significant link between migraines and IBS globally. This identifies an association that needs to be investigated in a nationwide manner. This study aims to observe the association and the relationship between migraine and irritable bowel syndrome in Saudi Arabia. A cross-sectional study was conducted between March 2021 to June 2021 among the general population of Saudi Arabia, whose ages are 15 years old or greater. The data collection tools included MS-Q for migraine symptoms, MIGSEV scale for severity of migraine, and The IBS module of the Rome IV Diagnostic Questionnaire (R4DQ) for IBS symptoms and its subtype. With a total of 2802 participants, the majority of the study sample were males, who constituted 52.5%. Among the study's sample, the prevalence of migraine consisted of 27.4%, and the prevalence of IBS was 16.4%. The odds of having IBS in migraineurs were much higher than in those without migraines (OR 4.127; 95% CI 3.325-5.121), and the association was statistically significant (P<0.001). In conclusion, there is a strong association between migraine and irritable bowel syndrome in Saudi Arabia.
REVIEW | doi:10.20944/preprints202012.0745.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Migraine; acute care; emergency department; analgesic; triptan; opioid and NSAID
Online: 30 December 2020 (07:55:04 CET)
Migraine is one of the leading causes of disability worldwide [1,2]and patients with acute migraine frequently present to emergency departments (ED). The current literature suggests that ED treatment of migraine headache varies across institutions [4-7]. Considering this, we conducted a scoping review to summarize trends in medication prescribing patterns for acute migraine treatment in the ED setting. Trends were evaluated for factors influencing treatment choices, with particular attention placed on opioids and migraine specific therapy. This scoping review was based on the Arksey and O'Malley methodological frameworkand included studies published between 1 January 2000 until 31 May 2020. 14 publications met the inclusion criteria. The most common classes of medication prescribed were often anti-emetics or Non-steroidal anti-inflammatory drugs (NSAID), but rates varied between studies. There was a concerning trend towards an underutilization of triptans and overutilization of opiates. The use of specific clinical goals of treatment (e.g. two-hour pain free freedom response) was also not evident. Additionally, 88% (n=8) of the 9 studies commenting on adherence to hospital or evidence-based guidelines stated that practices were non-adherent. Overall, the reviewed literature reveals treatment practices for acute migraine in the ED are heterogeneous and deviate from established international recommendations.
ARTICLE | doi:10.20944/preprints202011.0631.v1
Subject: Medicine & Pharmacology, Allergology Keywords: tension-type headache; migraine; neck and shoulder pain; ibuprofen; caffeine
Online: 25 November 2020 (10:51:30 CET)
As neck and/or shoulder pain (NSP) frequently occur together with tension-type headache (TTH) and migraine, we explored how concomitant NSP affects perceived treatment responses to an analgesic. An anonymous survey was performed among 895 TTH and migraine sufferers who used the analgesic 400 mg ibuprofen/100 mg caffeine. NSP was relatively abundant among patients (42.4% for TTH; 39.2% for migraine), and associated with >1 additional day with headache per month. Reported pain reduction was independent from NSP for TTH and migraine. More patients became pain-free at 2 h in migraine with NSP (42.9%) compared to migraine without NSP (32.2%), which is different from TTH with NSP (60.6%) and TTH without NSP (71.4%). For both, migraine and TTH, a recurrence of headache on the same day was more prevalent in those with concomitant NSP leading to a greater likelihood of taking a second dose of the analgesic. NSP frequently occurs together with TTH and migraine patients. In migraine, NSP seems to be associated with a better treatment response at 2 h. The more frequent recurrence of pain in those with concomitant NSP indicates that NSP makes both headache types worse. Further studies are needed to substantiate these effects.
REVIEW | doi:10.20944/preprints202104.0794.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Ketogenic Diets; Ketosis; Ketones; Consensus Statement; Position Paper; Headache; Migraine; Cluster Headache
Online: 30 April 2021 (15:38:37 CEST)
Headaches are among the most prevalent and disabling disorders and there are several patients’ unmet needs in current pharmacological options, while a growing interest is focusing on nutritional approaches as non-pharmacological treatments. Among these, the most promising seems to be the ketogenic diet (KD). Exactly 100 years ago, KD was used to treat pediatric forms of drug-resistant epilepsy, but progressively applications of this diet also involved adults and other neurological disorders. Evidence of KD effectiveness in migraine comes from 1928, but in the last years different groups of research and clinicians paid attention to this therapeutic option to treat patients with drug resistant migraine and cluster headache, and/or comorbid with metabolic syndrome. Here we describe all the existing evidence on the potential benefits of KDs in headaches, explore in deep all the potential mechanisms of action involved in the efficacy, and synthesize results of working meetings of an Italian panel of experts on this topic. Aim of the working group is the creation of a consensus on indications and clinical practice to treat with KDs patients with headache. The results here we present are the base for further improvement in the knowledge and application of KDs in the treatment of headaches.
ARTICLE | doi:10.20944/preprints202103.0760.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Dizziness; Vertigo; Migraine Disorders; Interdisciplinary Communication; Headache; Medulloblastoma; Lyme Neuroborreliosis; Somatoform Disorders; Child; Adolescent
Online: 31 March 2021 (11:35:13 CEST)
Objective: The causes of vertigo and dizziness in children are diverse and require attention from various specialists. Numerous authors have reported that the commonest type of vertigo in children is migraine-associated vertigo (vestibular migraine and benign paroxysmal vertigo of childhood - BPV). We aimed to check whether this could be applied to our group of patients. Materials and methods: A retrospective case series of 257 consecutive pediatric vertigo and diz-ziness patients referred to the tertiary pediatric ENT clinic from 2015 to 2020. Patients received a complete audiovestibular workup and were referred to pediatric neurologists and other special-ists depending on the signs and symptoms. Results: Of 257 children aged 1-17 years, almost one fifth of them, 49/257 (19.1 %) had a central type of vertigo, 20/257 of them (7.8%) had benign paroxysmal vertigo of childhood and 4/257 (1.6%) had a migrainous type of vertigo. Most of the children, 112/257 (43.6%), remained unclas-sified, without a final diagnosis. Conclusion: Due to the numerous possible causes, a child presenting with dizziness and vertigo requires a multidisciplinary approach. In the majority of cases, vertigo spells are self-limiting. They stop spontaneously and sometimes remain clinically undiagnosed. The most prevalent reasons for pediatric vertigo may be temporary hemodynamic (vaso-vagal) and psychological imbalance.
CASE REPORT | doi:10.20944/preprints202301.0469.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: anti-calcitonin gene-related peptide monoclonal antibodies; cluster headache; migraine; real-world; galcanezumab; fremanezumab; comorbidity
Online: 26 January 2023 (04:24:39 CET)
A new treatment option for cluster headache (CH) prevention is needed. Monoclonal antibodies (mABs) against calcitonin gene-related peptide (CGRP) ligands are used as a preventative treatment for migraine. Considering the CGRP’s role in the CH attack’s ignition and upkeep, fremanezumab and galcanezumab have been evaluated for CH preventative treatment. However, only high-dose (300 mg) galcanezumab was proven for episodic CH prevention. We herein report 3 cases of migraine and comorbid CH with previous failures of preventive treatments. The 2 cases were treated with fremanezumab and the one with non-high-dose galcanezumab. All 3 cases showed good results not only on migraine but also on CH attacks. Our report suggested the efficacy of CGRP-mABs for CH prevention. Our cases differed from the cases in the phase 3 trials of CGRP-mABs for CH prevention in the following 2 points. First, the patients had both migraine and comorbid CH. Second, the combined use of CGRP-mABs with preventative drugs for CH, such as verapamil and/or prednisolone, was performed. Future accumulation of real-world data may prove the efficacy of CGRP-mABs for CH prevention.
REVIEW | doi:10.20944/preprints202210.0083.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: epigenetics; TRP channels; TRPA1; pain transmission; neuropathic pain; neurogenic inflammation; migraine; DNA methylation; histone modification; micro RNA
Online: 7 October 2022 (15:21:34 CEST)
Background: Transient receptor potential cation channel subfamily A member 1 (TRPA1) is expressed in trigeminal neurons and brain regions important in migraine pathogenesis and is activated by many migraine triggers. Epigenetic regulation of TRPA1 expression is important in pain transmission and neurogenic inflammation.Findings: TRPA1 channels change noxious stimuli into pain signals with the involvement of epigenetic regulation, including DNA methylation, histone modifications, and effects of micro RNAs (miRNAs) and long non-coding RNAs. TRPA1 may change epigenetic profile of many pain-related genes as it may modify enzymes establishing the epigenetic profile and expression of non-coding RNAs. TRPA1 may induce the release of calcitonin gene related peptide (CGRP), from trigeminal neurons and dural tissue. Therefore, epigenetic regulation of TRPA1 may play a role in efficacy and safety of anti-migraine therapies targeting TRP channels and CGRP. TRPA1 is also involved in neurogenic inflammation, important in migraine. The fundamental role of TRPA1 in inflammatory pain transmission may be epigenetically regulated. Conclusions: Epigenetic connections of TRPA1 may play a role in efficacy and safety of anti-migraine therapy targeting TRP channels or CGRP and they should be further explored for efficient and safe antimigraine treatment.
ARTICLE | doi:10.20944/preprints202301.0509.v1
Subject: Social Sciences, Education Studies Keywords: education; medication-overuse headache (MOH); migraine; online; prevention; rational analgesic-use for headache; social networking services; social media
Online: 28 January 2023 (02:47:04 CET)
Introduction Headache is a common public health problem, but its burden could be avoided by raising headache awareness and the appropriate use of acute medication and prophylactic medication. Few reports on raising headache awareness in the general public have been reported, and there are no reports on headache awareness campaigns through social networking services (SNS), or social media, in Japan. We prospectively performed a headache awareness campaign from March 2022 through 2 SNS, targeting nurse and wind instrumental musicians, because they are with high headache prevalence. Methods Through the 2 SNS, the article and video were distributed, respectively. The article and video described the 6 important topics for the general public about headaches, which were described in the Clinical Practice Guideline for Headache Disorders 2021. Just after reading or watching them as e-learning, we performed online questionnaire sheets to investigate the awareness of the 6 topics through the 2 SNS. The awareness of the 6 topics before and after the campaign was evaluated. Results In the SNS nurse-senka, we obtained 1191 responses. Women comprised 94.4%, and the median (range) age was 45 (20 to 71) years old. Headache sufferers were 63.8%, but only 35.1% had consulted doctors. In the SNS Creatone, we got the response from 134 professional musicians, with 77.3% of women. The largest number of respondents were in their 20s (range 18-60 years old). Headache sufferers were 87.9%. Of them, 36.4% had consulted doctors, 24.2% were medication-overuse headache. The ratios of individuals who were aware of the 6 topics significantly increased from 15.2%-47.0% to 80.4-98.7% after the online questionnaire in both SNS (p < 0.001, all). Conclusions We conducted this headache awareness campaign through e-learning and an online survey via 2 SNS. The ratios of individuals who were aware of the 6 topics about headaches significantly increased 1 month after e-learning. Our results suggest that e-learning and online survey can improve headache awareness. The materials in this campaign can be installed into smartphone applications and further spread on SNS, leading to strong influence. With rapid digital transformations such as online telemedicine and artificial intelligence diagnosis, raising awareness will be more efficient and effective and should be important.
REVIEW | doi:10.20944/preprints202301.0034.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: migraine; neuropathic pain; calcitonin gene-related peptide (CGRP); kynurenine; glia; cytokines; neuroinflammation; transient receptor potential (TRP) ion channels; endocannabinoids
Online: 4 January 2023 (01:53:45 CET)
Migraine and neuropathic pain (NP) are evocative of painful, disabling, chronic conditions which exhibit resembling symptoms and thus considered to share a common etiology. Calcitonin gene-related peptide (CGRP) has gained credit as a target for migraine management; nevertheless, the efficacy and the applicability of CGRP modifiers warrant search for more effective therapeutic targets for pain management. This scoping review overviews human studies of common pathogenic factors in migraine and NP to explore potential novel therapeutic targets. CGRP causes inflammation in the meninges; monoclonal antibodies and inhibitors target CGRP. Gluta-mate-induced hyperexcitability and subsequent sensitization are closely linked to an alteration of the tryptophan (Trp)-kynurenine (KYN) metabolic system; the Trp-KYN system may serve as a potential target. Microglial overaction is observed in migraine and NP; modifying the microglial activity may be a possible approach. Cytokine-induced inflammation is a leading hypothesis of the pathogenesis of the conditions; alleviating neuroinflammation may complement a pain-relieving armamentarium. Transient receptor potential (TRP) ion channels evoke the release of several substances; TRP ion channels may potentially emerge as new targets. The endocannabinoid system plays a major role in the pain trafficking pathway; modification of the system may open a new path toward discovery of new analgesics. Here we highlight the mechanism of those common pathogenic factors to explore therapeutic targets for innovative pain management in migraine and NP.