Expression of Selected microRNAs in Migraine: A New Class of Possible Biomarkers of Disease?

Preliminary but convergent findings suggest a role for microRNAs (miRNAs) in the generation and maintenance of chronic pain and migraine. Initial observations showed that serum levels of miR-382-5p and miR-34a-5p expression were increased in serum during the migraine attack, with miR-382-5p increasing in the interictal phase as well. By contrast, miR-30a-5p levels were lower in migraine patients compared to healthy controls. Of note, antimigraine treatments proved to be capable of influencing the expression of these miRNAs. Altogether, these observations suggest that miRNAs may represent migraine biomarkers, but several points are yet to be elucidated. A major concern is that these miRNAs are altered in a broad spectrum of painful and non-painful conditions, and thus it is not possible to consider them as truly "migraine-specific" biomarkers. We feel that these miRNAs may represent useful tools to uncover and define different phenotypes across the migraine spectrum with different treatment susceptibilities and clinical features, although further studies are needed to confirm our hypothesis. In this narrative review we provide an update and a critical analysis of available data on miRNAs and migraines in order to propose possible interpretations. Our main objective is to stimulate research in an area that holds promise when it comes to providing reliable biomarkers for theoretical and practical scientific advances

COVID-19 in patients with Myasthenia Gravis: epidemiology and disease course

COVID-19, a disease caused by SARS-CoV-2 infection, has become a global pandemic. Patients with myasthenia gravis (MG), often treated with immunosuppressants, might be at higher risk of developing COVID-19 and of demonstrating a severe disease course. We aimed to study prevalence and describe features of COVID-19 in MG patients

Gender-related stress factors and emotional perception in migraine: a structured online questionnaire in migraine patients and controls

Background: While migraine is markedly prevalent in women, gender-related phenotype differences were rarely assessed. For this reason, we investigated, through a multicenter observational cross-sectional study, based on an online questionnaire, gender-related differences in stress factors, emotions, and pain perception in migraine patients and controls and their impact on migraine severity. Methods: The study was designed as an online questionnaire. The link was emailed to healthy subjects (C) and migraine patients (MIG) (age 18-75, education ≥ 13 years) recruited during the first visit in 8 Italian Headache Centers adhering to Italian Society for Headache Study (SISC). The questionnaire included personal/social/work information, the Perceived Stress Scale, the Romance Quality Scale, the Emotion Regulation Questionnaire, the Beck Anxiety Inventory, the Body Perception Questionnaire, the pain perception, and a self-assessment of migraine severity in the last 3 months. Results: 202 MIG and 202 C completed the survey. Independently from gender, migraine was characterized by higher pain sensitivity and more severe partner relationships. The female gender, in MIG, exhibited higher anxiety scores, body awareness, and reduced emotional suppression. Body awareness and emotional suppression were discriminating factors between genders in control and migraine groups without relevant influence on disease features. Perceived perception of migraine severity was similar between genders. Conclusion: Gender-related emotional and stress factors did not contribute to delineate a distinct phenotype in migraine men and women. The possible impact of emotional and stress factors characterizing genders could be considered for a single case-tailored therapeutic approach

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

The role of Stroke-Induced Immunosuppression as predictor of functional outcome in the neurorehabilitation setting

<p>This is a prospective observational study.</p><p>•             The final cohort was composed of 96 patients admitted for stroke rehabilitation at the Neurorehabilitation Unit of the IRCCS Mondino Foundation. </p><p>•             At admittance (T0) and discharge (T1) from neurorehabilitation we assessed presence of lymphopenia through NLR. NLR 5 at T0 defined the stroke-induced immunodepression group (SII) and NLR < 5 defined the Immunocompetent group (IC). At T0 and T1 we also collected functional scales (Functional Independence Measure (FIM) and Barthel Index), motor performance scales (Tinetti Balance Score and Hauser Ambulation Index) and neurological scales (NIHSS). </p><p>•             The occurrence of infections during hospitalization was also monitored.</p&gt

Searching for the Predictors of Response to BoNT-A in Migraine Using Machine Learning Approaches

OnabotulinumtoxinA (BonT-A) reduces migraine frequency in a considerable portion of patients with migraine. So far, predictive characteristics of response are lacking. Here, we applied machine learning (ML) algorithms to identify clinical characteristics able to predict treatment response. We collected demographic and clinical data of patients with chronic migraine (CM) or high-frequency episodic migraine (HFEM) treated with BoNT-A at our clinic in the last 5 years. Patients received BoNT-A according to the PREEMPT (Phase III Research Evaluating Migraine Prophylaxis Therapy) paradigm and were classified according to the monthly migraine days reduction in the 12 weeks after the fourth BoNT-A cycle, as compared to baseline. Data were used as input features to run ML algorithms. Of the 212 patients enrolled, 35 qualified as excellent responders to BoNT-A administration and 38 as nonresponders. None of the anamnestic characteristics were able to discriminate responders from nonresponders in the CM group. Nevertheless, a pattern of four features (age at onset of migraine, opioid use, anxiety subscore at the hospital anxiety and depression scale (HADS-a) and Migraine Disability Assessment (MIDAS) score correctly predicted response in HFEM. Our findings suggest that routine anamnestic features acquired in real-life settings cannot accurately predict BoNT-A response in migraine and call for a more complex modality of patient profiling

Potential Contribution of Hypertension to Evolution of Chronic Migraine and Related Mechanisms

Aims: To investigate the potential contributions of diastolic and systolic blood pressure (BP) and the circadian rhythm of BP to chronic migraine evolution. Methods: This cross-sectional study included four groups of patients selected based on migraine frequency (high frequency ≥ 10 days per month and low frequency < 10) and on the presence of hypertension. Among-group and pairwise comparisons were carried out to investigate potential neurophysiologic differences in the cerebral vessel reactivity to a nitroglycerin test, in autonomic balance (tilting test), and BP circadian rhythm. Results: A more marked decrease in cerebral blood flow velocity was observed in hypertensive high-frequency migraineurs compared to all other groups (P = .037). Moreover, a smaller decrease in vagal tone was recorded in the orthostatic position in hypertensive subjects, whether they were high- (P = .032) or low-frequency migraineurs (P = .014), with a consistently higher vagal to sympathetic tone ratio (P = .033). Finally, in nonhypertensive subjects, a higher but not significant prevalence of systolic nondippers was detected in high-frequency migraineurs (67%) compared to low-frequency subjects (25%; P = .099). Conclusion: These findings suggest that hypertension may contribute to the chronic evolution of headache with mechanisms shared with migraine; ie, vascular tone alteration and autonomic dysregulation