COMPLICATED MIGRAINE

Migraine is a chronic paroxysmal neurological disease characterized by attacks of moderate or severe headache accompanied by reversible neurologic and systemic symptoms. Although not life threatening, migraine can cause disability in the productive population. Migraine sufferers generally have a family history of migraine so that migraine is considered a genetic disease. Endogenous psychological factors such as stress or fatigue are the main triggers for migraine. Migraine pathophysiology involves various parts of the brain so that migraine symptoms are complex. Management of acute migraine can be done pharmacologically and non-pharmacologically. Migraine preventive management is needed if the patient has a chronic migraine or does not respond to abortive treatment.

Chronic Migraine Pathophysiology and Treatment: A Review of Current Perspectives

Chronic migraine is a disabling neurological disorder that imposes a considerable burden on individual and socioeconomic outcomes. Chronic migraine is defined as headaches occurring on at least 15 days per month with at least eight of these fulfilling the criteria for migraine. Chronic migraine typically evolves from episodic migraine as a result of increasing attack frequency and/or several other risk factors that have been implicated with migraine chronification. Despite this evolution, chronic migraine likely develops into its own distinct clinical entity, with unique features and pathophysiology separating it from episodic migraine. Furthermore, chronic migraine is characterized with higher disability and incidence of comorbidities in comparison to episodic migraine. While existing migraine studies primarily focus on episodic migraine, less is known about chronic migraine pathophysiology. Mounting evidence on aberrant alterations suggest that pronounced functional and structural brain changes, central sensitization and neuroinflammation may underlie chronic migraine mechanisms. Current treatment options for chronic migraine include risk factor modification, acute and prophylactic therapies, evidence-based treatments such as onabotulinumtoxinA, topiramate and newly approved calcitonin gene-related peptide or receptor targeted monoclonal antibodies. Unfortunately, treatments are still predominantly ineffective in aborting migraine attacks and decreasing intensity and frequency, and poor adherence and compliance with preventative medications remains a significant challenge. Novel emerging chronic migraine treatments such as neuromodulation offer promising therapeutic approaches that warrant further investigation. The aim of this narrative review is to provide an update of current knowledge and perspectives regarding chronic migraine background, pathophysiology, current and emerging treatment options with the intention of facilitating future research into this debilitating and largely indeterminant disorder.

Geographical, Molecular, and Computational Analysis of Migraine-Causing Genes

Migraine is a re-occurring type of headache and causes moderate-to-severe pain that is troubling or pulsing. The pain occurs in half of the head, and common symptoms are photophobia, phonophobia, nausea, depression, anxiety, vomiting, etc. This study evaluates the prevalence of migraine and responsible genes through molecular modeling in the region of Bahawalpur, Pakistan. This research was aimed to determine the prevalence of migraine-causing genes in the population of Bahawalpur and also to do molecular and in-silico analysis of migraine-causing gene as no similar research was conducted before. The disease was characterized and diagnosed under the criteria of the Second Edition of the International Classification of Headache Disorders and molecular identification of migraine-causing genes, i.e. GRIA1, GRIA3, and ESR1, by PCR amplification. The total number of samples collected for migraine patients was 230, out of which 30 were positive for PCR amplification of the genes GRIA1, GRIA3, and ESR1. Therapeutic potentials of commercial drugs, namely Cyclobenzaprine, Divalproex, Ergotamine, and Sumatriptan, were analyzed in silico through molecular docking. Ergotamine demonstrated the highest binding affinity of [Formula: see text]8.4 kcal/mol for the target molecule and, hence, the highest potential. The bivariate analysis showed that the prevalence of migraine concerning gender and age was significantly correlated ([Formula: see text], [Formula: see text]). It was observed that almost 31.4% of women suffered from headaches daily, 70% weekly, 28.1% monthly, and 23.5% rarely. Comparatively, only 8.3% of males suffered from daily headaches, 34% weekly, 12.8% monthly, and 14.9% rarely. The study shows promising results and encourages future researchers to conduct such a comprehensive epidemiological study on an even larger population to justify a more precise association of risk factors involved in migraine pathophysiology.

Association between response to triptans and response to erenumab: real-life data

Background Triptans and erenumab are both migraine-specific agents acting on the calcitonin gene-related peptide pathway. Therefore, response to triptans might be associated with response to erenumab. Main body In our study, consecutive patients referring to the Headache Centers of the Abruzzo region from January 2019 to March 2020 and treated with erenumab were interviewed about past use and efficacy of triptans. Triptan users were classified as ‘triptan responders’ if they were headache-free 2 h after treating ≥3 migraine attacks with ≥1 triptan. We considered patients as ‘erenumab responders’, if they had a ≥ 50% mean reduction in monthly migraine days between the 4th and the 6th month from treatment start compared with baseline. Of 91 triptan users, 73 (80.2%) were triptan responders and 58 (63.7%) were erenumab responders. The odds ratio of being erenumab responder was 3.64 (95% CI, 1.25–10.64) for triptan users as compared to non-users. (P = 0.014). Besides, starting erenumab improved triptan response in both erenumab responders and non-responders. Conclusions Our data of an association between response to triptans and response to erenumab can be useful for patient advice and to improve the understanding of migraine pathophysiology and treatment.

Cortical mechanisms in migraine

Migraine is the second most prevalent disorder in the world; yet, its underlying mechanisms are still poorly understood. Cumulative studies have revealed pivotal roles of cerebral cortex in the initiation, propagation, and termination of migraine attacks as well as the interictal phase. Investigation of basic mechanisms of the cortex in migraine not only brings insight into the underlying pathophysiology but also provides the basis for designing novel treatments. We aim to summarize the current research literatures and give a brief overview of the cortex and its role in migraine, including the basic structure and function; structural, functional, and biochemical neuroimaging; migraine-related genes; and theories related to cortex in migraine pathophysiology. We propose that long-term plasticity of synaptic transmission in the cortex encodes migraine.

Association between response to triptans and response to erenumab: real-life data

Background. Triptans and erenumab are both migraine-specific agents acting on the calcitonin gene-related peptide pathway. Therefore, response to triptans might be associated with response to erenumab. Main body. In our study, consecutive patients referring to the Headache Centers of the Abruzzo region from January 2019 to March 2020 and treated with erenumab were interviewed about past use and efficacy of triptans. Triptan users were classified as ‘triptan responders’ if they were headache-free 2 hours after treating ≥3 migraine attacks with ≥1 triptan. We considered patients as ‘erenumab responders’, if they had a ≥50% mean reduction in monthly migraine days between the 4th and the 6th month from treatment start compared with baseline. Of 91 triptan users, 73 (80.2%) were triptan responders and 58 (63.7%) were erenumab responders. The odds ratio of being erenumab responder was 3.64 (95% CI, 1.25-10.64) for triptan users as compared to non-users. (P=0.014). Besides, starting erenumab improved triptan response in both erenumab responders and non-responders. Conclusions. Our data of an association between response to triptans and response to erenumab can be useful for patient advice and to improve the understanding of migraine pathophysiology and treatment.