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    Serum concentration of magnesium as an independent risk factor in migraine attacks: a matched case-control study and review of the literature. Assarzadegan Farhad,Asgarzadeh Setareh,Hatamabadi Hamid R,Shahrami Ali,Tabatabaey Ali,Asgarzadeh Morteza International clinical psychopharmacology There is controversy over the role of magnesium in the etiology of migraine headaches. We aimed to evaluate and compare serum levels of magnesium between healthy individuals and those with migraine headaches during migraine attacks and between attacks to evaluate the role of magnesium in the etiology of migraine headaches. Forty patients with migraine headaches and 40 healthy individuals were enrolled in this matched case-control study. Malnutrition, digestive system disorders, history of smoking, drug abuse, and history of medications use were recorded at baseline. The pain scores of patients were measured and recorded based on a 10 cm visual analog scale. Subsequently, blood samples were collected at 8-10 in the morning to determine serum levels of magnesium. Analysis of variance, χ-test, and conditional logistic regression were used for data analysis. There were no significant differences in demographic data between the two groups. There were significant differences in magnesium serum levels between the three groups (1.09±0.2 mg/dl during migraine headaches; 1.95±0.3 mg/dl between the attacks; and 1.3±0.4 mh/dl in the control group; P<0.0001). Odds of acute migraine headaches increased 35.3 times (odds ratio=35.3; 95% confidence interval: 12.4-95.2; P=0.001) when serum levels of magnesium reached below the normal level. The odds in patients who are not in the acute attack phase were 6.9 folds higher (odds ratio=6.9; 95% confidence interval: 1.3-2.1; P=0.02). The serum level of magnesium is an independent factor for migraine headaches and patients with migraine have lower serum levels of magnesium during the migraine attacks and between the attacks compared with healthy individuals. 10.1097/YIC.0000000000000130
    Calcitonin gene-related peptide in migraine: from pathophysiology to treatment. Santos-Lasaosa S,Belvís R,Cuadrado M L,Díaz-Insa S,Gago-Veiga A,Guerrero-Peral A L,Huerta M,Irimia P,Láinez J M,Latorre G,Leira R,Pascual J,Porta-Etessam J,Sánchez Del Río M,Viguera J,Pozo-Rosich P Neurologia (Barcelona, Spain) INTRODUCTION:It has been observed in recent years that levels of such molecules as calcitonin gene-related peptide (CGRP) and, to a lesser extent, the pituitary adenylate cyclase-activating peptide are elevated during migraine attacks and in chronic migraine, both in the cerebrospinal fluid and in the serum. Pharmacological reduction of these proteins is clinically significant, with an improvement in patients' migraines. It therefore seems logical that one of the main lines of migraine research should be based on the role of CGRP in the pathophysiology of this entity. DEVELOPMENT:The Spanish Society of Neurology's Headache Study Group decided to draft this document in order to address the evidence on such important issues as the role of CGRP in the pathophysiology of migraine and the mechanism of action of monoclonal antibodies and gepants; and to critically analyse the results of different studies and the profile of patients eligible for treatment with monoclonal antibodies, and the impact in terms of pharmacoeconomics. CONCLUSIONS:The clinical development of gepants, which are CGRP antagonists, for the acute treatment of migraine attacks, and CGRP ligand and receptor monoclonal antibodies offer promising results for these patients. 10.1016/j.nrl.2019.03.013
    Nonclinical safety evaluation of erenumab, a CGRP receptor inhibitor for the prevention of migraine. Bussiere Jeanine L,Davies Rhian,Dean Charles,Xu Cen,Kim Kyung Hoon,Vargas Hugo M,Chellman Gary J,Balasubramanian Ganesh,Rubio-Beltran Eloisa,MaassenVanDenBrink Antoinette,Monticello Thomas M Regulatory toxicology and pharmacology : RTP Calcitonin gene-related peptide (CGRP) and its receptor have been implicated as a key mediator in the pathophysiology of migraine. Thus, erenumab, a monoclonal antibody antagonist of the CGRP receptor, administered as a once monthly dose of 70 or 140 mg has been approved for the preventive treatment of migraine in adults. Due to the species specificity of erenumab, the cynomolgus monkey was used in the pharmacology, pharmacokinetics, and toxicology studies to support the clinical program. There were no effects of erenumab on platelets in vitro (by binding, activation or phagocytosis assays). Specific staining of human tissues with erenumab did not indicated any off-target binding. There were no erenumab-related findings in a cardiovascular safety pharmacology study in cynomolgus monkeys or in vitro in human isolated coronary arteries. Repeat-dose toxicology studies conducted in cynomolgus monkeys at dose levels up to 225 mg/kg (1 month) or up to 150 mg/kg (up to 6 months) with twice weekly subcutaneous (SC) doses showed no evidence of erenumab-mediated adverse toxicity. There were no effects on pregnancy, embryo-fetal or postnatal growth and development in an enhanced pre-postnatal development study in the cynomolgus monkey. There was evidence of placental transfer of erenumab based on measurable serum concentrations in the infants up to 3 months post birth. The maternal and developmental no-observed-effect level (NOEL) was the highest dose tested (50 mg/kg SC Q2W). These nonclinical data in total indicate no safety signal of concern to date and provide adequate margins of exposure between the observed safe doses in animals and clinical dose levels. 10.1016/j.yrtph.2019.05.013
    The Role of Magnesium in Pathophysiology and Migraine Treatment. Dolati Sanam,Rikhtegar Reza,Mehdizadeh Amir,Yousefi Mehdi Biological trace element research Migraine is one of the most common recurrent types of headache and is the seventh cause of disability. This neurological disorder is characterized by having pain in head and other various symptoms such as nausea, emesis, photophobia, phonophobia, and sometimes visual sensory disorders. Magnesium (Mg) is a necessary ion for human body and has a crucial role in health and life maintenance. One of the main roles of Mg is to conserve neurons electric potential. Therefore, magnesium deficiency can cause neurological complications. Migraine is usually related to low amounts of Mg in serum and cerebrospinal fluid (CSF). Deficits in magnesium have significant role in the pathogenesis of migraine. Mg has been extensively used in migraine prophylaxis and treatment. This review summarizes the role of Mg in migraine pathogenesis and the potential utilizations of Mg in the prevention and treatment of migraine with the emphasis on transdermal magnesium delivery. 10.1007/s12011-019-01931-z
    Evaluation of serum uric levels in migraine. Yazar Tamer,Yazar Hülya Olgun,Aygün Ali,Karabacak Volkan,Altunkaynak Yavuz,Kirbaş Dursun Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology OBJECTIVE:In our study, the aim was to identify the serum uric acid levels, a marker of oxidative stress, according to migraine subtypes (aura/without aura and episodic/chronic migraine). METHOD:The study included 300 migraine patients and 150 healthy controls for a total of 450 individuals. Migraine and subtypes were diagnosed according to International Classification of Headache Disorders-2013 criteria. Patients were evaluated during attendance at the neurology clinic. RESULTS:Our patient group was 77.0% female and disease duration was 9.2 ± 7.2 years. Our control group comprised 77.3% females. The age intervals in the patient and control groups were 36.4 ± 10.4 years and 36.0 ± 8.1 years. There was no statistically significant difference between our control and patient groups in terms of age and gender (p = .937 and p = .655). The serum UA, ferritin, and urea levels in our patient group were found to be significantly low compared to the healthy control group (p < .001). The serum UA levels in the migraine and control groups were 3.7 ± 0.7 and 4.6 ± 0.7 mg/dL, respectively (p < .001). There were no statistically significant differences observed between serum uric acid levels and other blood parameters between aura/without aura and episodic/chronic migraine subtypes (p > .05). CONCLUSION:Our study supports the hypothesis that the oxidative stress marker of serum uric acid levels may be associated with migraine diagnosis, concluding that serum uric acid levels were not significant for migraine subtypes. 10.1007/s10072-020-04598-w