Phd in SENSORINEURAL PLASTICITY

Thesis title: Morphometric Similarity Mapping nell’Emicrania Senza Aura in Età Pediatrica: Studio RM di Plasticità Neurosensoriale

Morphometric Similarity Mapping in Pediatric Migraine Without Aura: An MRI Study of Sensorineural Plasticity Background: Recent literature supports the hypothesis that pediatric migraine without aura is caused by structural and functional alterations in the cerebral connectome. MSM (Morphometric Similarity Mapping), which has never been applied to pediatric migraine without aura, is an advanced and non-invasive MRI (Magnetic Resonance Imaging) technique which identifies anomalies of the brain cortex and cerebral connectivity through the analysis of three groups of morphometric features related to grey matter, cortical curvature, and myelination. Aims: The primary aims of this study were: 1) to identify statistically significant differences in Morphometric Similarity Networks (MSN) between pediatric patients affected by migraine without aura and age- and sex-matched healthy controls; 2) to identify statistically significant differences in MSN within subgroups of pediatric patients stratified by age, sex, and clinical manifestations of migraine without aura. The secondary objective of the study was: 3) to correlate any differences identified in MSN between patients and healthy controls, and within patient subgroups, with the demographic and clinical characteristics of the patients themselves. Methods: Patients diagnosed with migraine without aura according to the ICHD-3 (International Classification of Headache Disorders) and healthy controls aged 6–17 years were retrospectively recruited from the archives of the Bambino Gesù Children’s Hospital, based on the following inclusion criteria: normal and high-quality MRI scans, normal neurological examinations, and absence of comorbidities. Data from 3D T1 MPRAGE (Magnetization Prepared Rapid Gradient Echo Imaging) and DWI (Diffusion-Weighted Imaging) sequences were processed to obtain eleven cortical parameters divided into three groups of morphometric features related to grey matter, cortical curvature, and myelination, for MSM analysis. Global mean Morphometric Similarity (MS) and regional mean MS were calculated. Independent linear regression analyses were then performed for all subjects and for patient subgroups in both global and regional models, followed by ANOVA (Analysis of Variance) with False Discovery Rate (FDR) correction and a significance threshold of p< 0.05. For significant predictors, a post hoc analysis was performed using the Benjamini-Hochberg method. Results: The final cohort included 83 patients affected by migraine without aura (Females: 46) and 81 controls (Females: 40) aged 6–17 years. MSM identified significant differences in MSN between patients with migraine without aura and healthy controls, as well as within subgroups of patients divided according to clinical and demographic parameters. Notably, the most significant differences in MSN among patients were correlated with biological sex. The brain networks exhibiting the most prominent alterations included the executive function network, the nociceptive network, and the default mode network (DMN). Conclusions: The MSM analysis revealed significant alterations in MSN between pediatric patients affected by migraine without aura compared and healthy controls, and within subgroups of patients divided by demographic and clinical parameters, demonstrating that migraine shapes the cerebral connectome and promotes neuronal plasticity. In particular, biological sex emerged as the most relevant parameter both in the comparison between patients and controls and among subgroups of patients with migraine without aura, supporting the hypothesis of a “sex-specific phenotype.” The corresponding differences in MSN identified in the executive function network, nociceptive network, and DMN may underlie the chronicization of migraine symptoms, leading to a reduced quality of life in pediatric patients. The identification of early in vivo neuroimaging biomarkers of pediatric migraine, correlated with cortical and connectivity abnormalities in patients affected by migraine without aura, and the subsequent stratification of patients based on demographic and clinical characteristics, are crucial to providing early and personalized therapy that can substantially improve the quality of life of pediatric patients affected by migraine without aura.