Table_1_Neuroimaging markers of Alice in Wonderland syndrome in patients with migraine with aura.docx

BackgroundThe Alice in Wonderland syndrome (AIWS) is a transient neurological disturbance characterized by sensory distortions most frequently associated with migraine in adults. Some lines of evidence suggest that AIWS and migraine might share common pathophysiological mechanisms, therefore we set out to investigate the common and distinct neurophysiological alterations associated with these conditions in migraineurs.MethodsWe conducted a case–control study acquiring resting-state fMRI data from 12 migraine patients with AIWS, 12 patients with migraine with typical aura (MA) and 24 age-matched healthy controls (HC). We then compared the interictal thalamic seed-to-voxel and ROI-to-ROI cortico-cortical resting-state functional connectivity between the 3 groups.ResultsWe found a common pattern of altered thalamic connectivity in MA and AIWS, compared to HC, with more profound and diffuse alterations observed in AIWS. The ROI-to-ROI functional connectivity analysis highlighted an increased connectivity between a lateral occipital region corresponding to area V3 and the posterior part of the superior temporal sulcus (STS) in AIWS, compared to both MA and HC.ConclusionThe posterior STS is a multisensory integration area, while area V3 is considered the starting point of the cortical spreading depression (CSD), the neural correlate of migraine aura. This interictal hyperconnectivity might increase the probability of the CSD to directly diffuse to the posterior STS or deactivating it, causing the AIWS symptoms during the ictal phase. Taken together, these results suggest that AIWS in migraineurs might be a form of complex migraine aura, characterized by the involvement of associative and multisensory integration areas.</p

Table_3_Neuroimaging markers of Alice in Wonderland syndrome in patients with migraine with aura.docx

BackgroundThe Alice in Wonderland syndrome (AIWS) is a transient neurological disturbance characterized by sensory distortions most frequently associated with migraine in adults. Some lines of evidence suggest that AIWS and migraine might share common pathophysiological mechanisms, therefore we set out to investigate the common and distinct neurophysiological alterations associated with these conditions in migraineurs.MethodsWe conducted a case–control study acquiring resting-state fMRI data from 12 migraine patients with AIWS, 12 patients with migraine with typical aura (MA) and 24 age-matched healthy controls (HC). We then compared the interictal thalamic seed-to-voxel and ROI-to-ROI cortico-cortical resting-state functional connectivity between the 3 groups.ResultsWe found a common pattern of altered thalamic connectivity in MA and AIWS, compared to HC, with more profound and diffuse alterations observed in AIWS. The ROI-to-ROI functional connectivity analysis highlighted an increased connectivity between a lateral occipital region corresponding to area V3 and the posterior part of the superior temporal sulcus (STS) in AIWS, compared to both MA and HC.ConclusionThe posterior STS is a multisensory integration area, while area V3 is considered the starting point of the cortical spreading depression (CSD), the neural correlate of migraine aura. This interictal hyperconnectivity might increase the probability of the CSD to directly diffuse to the posterior STS or deactivating it, causing the AIWS symptoms during the ictal phase. Taken together, these results suggest that AIWS in migraineurs might be a form of complex migraine aura, characterized by the involvement of associative and multisensory integration areas.</p

Comparison of immunological/inflammatory profiling between SBI, LI and controls.

<p>Data are given as median value (interquartile range) of cytokines blood levels (pg/mL).</p><p>P-values are reported for non-parametric ANOVA (adjusted for gender, age, vascular risk factors and co-medications considered as classes - antihypertensives, antidiabetics, statins, and anti-arrhythmic agents-). For significant overall group effect, p values of Bonferroni adjusted multiple comparisons are reported.</p>*<p>p<0.05 SBI vs. Controls;</p>†<p>p<0.05 SBI vs. LI;</p>‡<p>p<0.05 LI vs. Controls.</p><p>CTACK: cutaneous T-cell-attracting chemokine; HGF: hepatocyte growth factor; ICAM1: intercellular adhesion molecule-1; IL12p40: interleukin-12 p40; IL-16: interleukin-16; IL18: interleukin-18; IL2Ra: interleukin-2 receptor-alpha; IL3: interleukin-3; INFα2: interferon alpha-2; LI: patients with lacunar stroke; MCP1: monocyte chemoattractant protein-1; MIF: macrophage migration inhibitory factor; MIG: monokine induced by gamma-interferon; SBI: patients with silent brain infarcts; SCF: stem cell factor; SCGFb: stem cell growth factor-b; SDF1a: stromal cell-derived factor-1a; TRAIL: tumor necrosis factor-α-related apoptosis-inducing ligand; VCAM1: vascular cell adhesion molecule-1.</p

Predictive values (pg/mL), AUC (95% CI), sensitivity and specificity of each analyte.

<p>Statistical significance for AUC is underlined.</p><p>ICAM1: intercellular adhesion molecule-1; IL-16: interleukin-16; IL18: interleukin-18; MIG: monokine induced by gamma-interferon; SCF: stem cell factor; SCGFb: stem cell growth factor-b. LI: lacunar stroke; SBI: silent brain infarcts.</p

ROC curves in SBI (continuous lines) and LI patients (broken lines) of each analyte, showing a statistically significant difference in the comparison among SBI, LI and Controls.

<p>Abbreviations: ICAM1: intercellular adhesion molecule-1; IL-16: interleukin-16; IL18: interleukin-18; MIG: monokine induced by gamma-interferon; SCF: stem cell factor; SCGFb: stem cell growth factor-b. LI: lacunar stroke; SBI: silent brain infarcts.</p

Post-hoc pairwise comparisons of immunological/inflammatory profiling between SBI, LI and healthy control subjects.

<p>Abbreviations: ICAM1: intercellular adhesion molecule-1; IL-16: interleukin-16; IL18: interleukin-18; MIG: monokine induced by gamma-interferon; SCF: stem cell factor; SCGFb: stem cell growth factor-b. LI: lacunar stroke; SBI: silent brain infarcts.</p

Characteristics of study population at baseline.

<p>Age is given as median (interquartile range). Gender and vascular risk factors are reported as absolute number of subjects (%). P-values are calculated using chi-square statistics (categorical variables) and Kruskal-Wallis statistics (continuous variables).</p><p>SBI: silent brain infarcts; LI: lacunar stroke.</p

Immunomodulatory and inflammatory activity of the investigated molecules.

<p>CTACK: cutaneous T-cell-attracting chemokine; HGF: hepatocyte growth factor, ICAM1: intercellular adhesion molecule-1; IL12p40: interleukin-12 p40; IL-16: interleukin-16; IL18: interleukin-18; IL2Ra: interleukin-2 receptor-alpha; IL3: interleukin-3; INFα2: interferon alpha-2; MCP1: monocyte chemoattractant protein-1; MIF: macrophage migration inhibitory factor; MIG: monokine induced by gamma-interferon; SCF: stem cell factor; SCGFb: stem cell growth factor-b; SDF1a: stromal cell-derived factor-1a; TRAIL: tumor necrosis factor-α-related apoptosis-inducing ligand; VCAM1: vascular cell adhesion molecule-1.</p