@article {973, title = {Structural brain changes in patients with persistent headache after COVID-19 resolution}, journal = {Journal of Neurology}, volume = {270}, year = {2023}, pages = {13-31}, abstract = {

Headache is among the most frequently reported symptoms after resolution of COVID-19. We assessed structural brain changes using T1- and diffusion-weighted MRI processed data from 167 subjects: 40 patients who recovered from COVID-19 but suffered from persistent headache without prior history of headache (COV), 41 healthy controls, 43 patients with episodic migraine and 43 patients with chronic migraine. To evaluate gray matter and white matter changes, morphometry parameters and diffusion tensor imaging-based measures were employed, respectively. COV patients showed significant lower cortical gray matter volume and cortical thickness than healthy subjects (p\thinspace\<\thinspace0.05, false discovery rate corrected) in the inferior frontal and the fusiform cortex. Lower fractional anisotropy and higher radial diffusivity (p\thinspace\<\thinspace0.05, family-wise error corrected) were observed in COV patients compared to controls, mainly in the corpus callosum and left hemisphere. COV patients showed higher cortical volume and thickness than migraine patients in the cingulate and frontal gyri, paracentral lobule and superior temporal sulcus, lower volume in subcortical regions and lower curvature in the precuneus and cuneus. Lower diffusion metric values in COV patients compared to migraine were identified prominently in the right hemisphere. COV patients present diverse changes in the white matter and gray matter structure. White matter changes seem to be associated with impairment of fiber bundles. Besides, the gray matter changes and other white matter modifications such as axonal integrity loss seemed subtle and less pronounced than those detected in migraine, showing that persistent headache after COVID-19 resolution could be an intermediate state between normality and migraine.

}, issn = {1432-1459}, doi = {10.1007/s00415-022-11398-z}, url = {https://doi.org/10.1007/s00415-022-11398-z}, author = {{\'A}lvaro Planchuelo-G{\'o}mez and Garc{\'\i}a-Azor{\'\i}n, David and Guerrero, {\'A}ngel L. and Rodr{\'\i}guez, Margarita and Aja-Fern{\'a}ndez, Santiago and de Luis-Garc{\'\i}a, Rodrigo} } @conference {968, title = {Long-term grey matter structural changes in the transition from chronic migraine to episodic migraine}, booktitle = {8th Congress of the European Academy of Neurology}, year = {2022}, month = {2022}, abstract = {

Background and aims: The objective was to assess grey matter longitudinal changes in patients with chronic migraine (CM) who reverse to episodic migraine (EM) compared to those who do not reverse.

Methods: High-resolution 3D brain T1-weighted Magnetic Resonance Imaging data were obtained twice from migraine patients. The first acquisition was performed immediately after the first visit to the Headache Unit, before taking preventive treatments. The second timepoint was at least three years after the first acquisition. From the longitudinal pipeline of FreeSurfer (v6.0), the mean values of cortical thickness, surface area and grey matter volume of 68 cortical, 14 subcortical regions and the cerebellum were extracted. Longitudinal changes between patients with CM and those who reversed to EM were assessed with linear
mixed-effects models, setting p\<0.05 (false discovery rate corrected) as threshold for statistical significance.

Results: 22 patients were included, and 10 of them (45.5\%) reversed to EM. No statistically significant differences of age (42.0+-9.0 years) and sex (21 women, 95.5\%) were found between patient groups. Higher statistically significant values of the three parameters in patients who reversed to EM were found in the pericalcarine, parietal, orbitofrontal cortex, and amygdala (Table 1, Figure 1). In contrast, lower values were detected in the cingulum, caudal middle frontal cortex, cerebellum, caudate nucleus and pallidum (Figure 2). In the insula, higher thickness but lower area was appreciated in patients who reversed.

Conclusion: Patients with CM who reverse to EM present distinct patterns of increased and decreased morphometric parameters propagated in the orbital frontal cortex and the cingulum, respectively.

Disclosure: Nothing to disclose.

}, author = {{\'A}lvaro Planchuelo-G{\'o}mez and Marchante-Re{\'\i}llo, Ginebra and Sierra, {\'A}lvaro and Garc{\'\i}a-Azor{\'\i}n, David and Mart{\'\i}n-Mart{\'\i}n, Carmen and de Luis-Garc{\'\i}a, Rodrigo and Aja-Fern{\'a}ndez, Santiago and Moro, Ra{\'u}l and Rodr{\'\i}guez, Margarita and Gonz{\'a}lez-Osorio, Y{\'e}sica and {\'A}ngel L. Guerrero} } @conference {937, title = {Gray matter cortical changes in patients with persistent headache after COVID-19 infection: an exploratory study}, booktitle = {International Headache Congress 2021}, year = {2021}, month = {2021}, publisher = {International Headache Society \& European Headache Federation}, organization = {International Headache Society \& European Headache Federation}, address = {Virtual Congress}, abstract = {

Objective: To evaluate gray matter alterations in patients with persistent headache after COVID-19 resolution.
Methods: Exploratory case-control study. Highresolution 3D brain T1-weighted Magnetic Resonance Imaging data were acquired in patients with persistent
headache after COVID-19 infection and healthy controls (HC). FreeSurfer (version 6.0) was employed to segment the T1-weighted images and extract the mean values of the cortical curvature (CC) and thickness (CT), surface area (SA) and gray matter volume (GMV) of 68 cortical regions. GMV comparisons were adjusted for intracranial volume. Significant results were considered with p \< 0.05 (False Discovery Rate corrected).
Results: Ten patients with persistent headache after COVID-19 (mean age: 53.8 +- 7.8 years; nine women) and 10 HC balanced for age and sex (mean age: 53.1 +- 7.0 years; nine women) were included in the study. Significant higher mean SA and GMV values were found in patients with persistent headache compared to HC in the bilateral medial orbitofrontal cortex, left rostral middle frontal gyrus, and right pars opercularis and superior frontal gyrus. In the patients, significant higher GMV in the right caudal anterior cingulate gyrus and SA values in five temporal, frontal and parietal regions were observed. No CC or CT changes were found.
Conclusions: Persistent headache after COVID-19 infection is related to gray matter cortical changes defined by higher GMV and SA values mainly localized in frontal regions.

}, url = {https://journals.sagepub.com/doi/pdf/10.1177/03331024211034005}, author = {{\'A}lvaro Planchuelo-G{\'o}mez and Garc{\'\i}a-Azor{\'\i}n, David and {\'A}ngel L. Guerrero and Santiago Aja-Fern{\'a}ndez and Rodr{\'\i}guez, Margarita and Moro, Ra{\'u}l and Rodrigo de Luis-Garc{\'\i}a} } @article {907, title = {Multimodal fusion analysis of structural connectivity and gray matter morphology in migraine}, journal = {Human Brain Mapping}, volume = {42}, year = {2021}, pages = {908-921}, abstract = {

No specific migraine biomarkers have been found in single-modality MRI studies. We aimed at establishing biomarkers for episodic and chronic migraine using diverse MRI modalities. We employed canonical correlation analysis and joint independent component analysis to find structural connectivity abnormalities that are related to gray matter morphometric alterations. The number of streamlines (trajectories of estimated fiber-tracts from tractography) was employed as structural connectivity measure, while cortical curvature, thickness, surface area, and volume were used as gray matter parameters. These parameters were compared between 56 chronic and 54 episodic migraine patients, and 50 healthy controls. Cortical curvature alterations were associated with abnormalities in the streamline count in episodic migraine patients compared to controls, with higher curvature values in the frontal and temporal poles being related to a higher streamline count. Lower streamline count was found in migraine compared to controls in connections between cortical regions within each of the four lobes. Higher streamline count was found in migraine in connections between subcortical regions, the insula, and the cingulate and orbitofrontal cortex, and between the insula and the temporal region. The connections between the caudate nucleus and the orbitofrontal cortex presented worse connectivity in chronic compared to episodic migraine. The hippocampus was involved in connections with higher and lower number of streamlines in chronic migraine. Strengthening of structural networks involving pain processing and subcortical regions coexists in migraine with weakening of cortical networks within each lobe. The multimodal analysis offers a new insight about the association between brain structure and connectivity.

}, keywords = {Brain, Magnetic Resonance Imaging, connectome, diffusion magnetic resonance imaging, migraine disorders}, doi = {https://doi.org/10.1002/hbm.25267}, url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/hbm.25267}, author = {{\'A}lvaro Planchuelo-G{\'o}mez and Garc{\'\i}a-Azor{\'\i}n, David and {\'A}ngel L. Guerrero and Santiago Aja-Fern{\'a}ndez and Rodr{\'\i}guez, Margarita and Rodrigo de Luis-Garc{\'\i}a} } @conference {939, title = {Resting-state functional alterations in patients with persistent headache after COVID-19 infection: an exploratory study}, booktitle = {International Headache Congress 2021}, year = {2021}, month = {2021}, publisher = {International Headache Society \& European Headache Federation}, organization = {International Headache Society \& European Headache Federation}, address = {Virtual Congress}, abstract = {

Objective: To evaluate resting-state functional alterations in patients with persistent headache after COVID-19 resolution.
Methods: Exploratory case-control study. Highresolution brain resting-state functional Magnetic Resonance Imaging data were acquired in patients with
persistent headache after COVID-19 infection and healthy controls (HC). CONN toolbox (version 17) was employed to assess the resting-state functional connectivity between 84 cortical and subcortical gray matter regions of interest. Significant results were considered with p \< 0.05 (Family Discovery Rate and seed-level corrected).
Results: Ten patients with persistent headache after COVID-19 (mean age: 53.8 +- 7.8 years; nine women) and 10 HC balanced for age and sex (mean age: 51.9 +- 6.6 years; nine women) were included in the study. Statistically significant higher functional connectivity was observed in the patients with persistent headache compared to HC in 10 connections. These connections were composed of an occipital region and another region that included the isthmus cingulate gyrus, a frontal or a parietal area. In the patients, significant lower functional connectivity was found in 12 connections between the cingulate and hippocampal gyri, parietal, temporal and frontal regions.
Conclusions: Patients with persistent headache after COVID-19 infection present strengthened functional connectivity with occipital regions and weakened functional connectivity between frontal, temporal and parietal regions.

}, url = {https://journals.sagepub.com/doi/pdf/10.1177/03331024211034005}, author = {{\'A}lvaro Planchuelo-G{\'o}mez and Garc{\'\i}a-Azor{\'\i}n, David and {\'A}ngel L. Guerrero and Santiago Aja-Fern{\'a}ndez and Rodr{\'\i}guez, Margarita and Moro, Ra{\'u}l and Rodrigo de Luis-Garc{\'\i}a} } @conference {938, title = {White matter microstructural alterations in patients with persistent headache after COVID-19 infection: an exploratory study}, booktitle = {International Headache Congress 2021}, year = {2021}, month = {2021}, publisher = {International Headache Society \& European Headache Federation}, organization = {International Headache Society \& European Headache Federation}, address = {Virtual Congress}, abstract = {

Objective: To evaluate white matter alterations in patients with persistent headache after COVID-19 resolution.
Methods: Exploratory case-control study. Highresolution brain diffusion Magnetic Resonance Imaging data were acquired in patients with persistent headache after COVID-19 infection and healthy controls (HC). Tract-Based Spatial Statistics was used to compare fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), radial diffusivity (RD) and the return-to-axial (RTAP), return-to-origin (RTOP) and return-to-plane probability (RTPP) between the groups. RTAP, RTOP and RTPP were obtained with a new approach called AMURA (https://www.lpi.tel.uva.es/AMURA). Significant results were considered with p \< 0.05 (Family-Wise Error corrected) and region size larger than 30 mm3.
Results: Ten patients with persistent headache after COVID-19 (mean age: 53.8 +- 7.8 years; nine women) and 10 HC balanced for age and sex (mean age: 53.1 +- 7.0 years; nine women) were included in the study. Significant higher AD and lower RTPP values were found in patients with persistent headache compared to HC in five regions from the corona radiata, and the external and internal capsule. In the patients, significant lower RTPP values were identified in six additional areas from the same tracts and the superior longitudinal fasciculus. No additional changes were found.
Conclusions: White matter axonal alterations are present in patients with persistent headache after COVID-19 infection.

}, url = {https://journals.sagepub.com/doi/pdf/10.1177/03331024211034005}, author = {{\'A}lvaro Planchuelo-G{\'o}mez and Garc{\'\i}a-Azor{\'\i}n, David and {\'A}ngel L. Guerrero and Santiago Aja-Fern{\'a}ndez and Rodr{\'\i}guez, Margarita and Moro, Ra{\'u}l and Rodrigo de Luis-Garc{\'\i}a} } @article {891, title = {Alternative Microstructural Measures to Complement Diffusion Tensor Imaging in Migraine Studies with Standard MRI Acquisition}, journal = {Brain Sciences}, volume = {10}, year = {2020}, month = {2020}, pages = {711}, abstract = {The white matter state in migraine has been investigated using diffusion tensor imaging (DTI) measures, but results using this technique are conflicting. To overcome DTI measures, we employed ensemble average diffusion propagator measures obtained with apparent measures using reduced acquisitions (AMURA). The AMURA measures were return-to-axis (RTAP), return-to-origin (RTOP) and return-to-plane probabilities (RTPP). Tract-based spatial statistics was used to compare fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity from DTI, and RTAP, RTOP and RTPP, between healthy controls, episodic migraine and chronic migraine patients. Fifty healthy controls, 54 patients with episodic migraine and 56 with chronic migraine were assessed. Significant differences were found between both types of migraine, with lower axial diffusivity values in 38 white matter regions and higher RTOP values in the middle cerebellar peduncle in patients with a chronic migraine (p \< 0.05 family-wise error corrected). Significantly lower RTPP values were found in episodic migraine patients compared to healthy controls in 24 white matter regions (p \< 0.05 family-wise error corrected), finding no significant differences using DTI measures. The white matter microstructure is altered in a migraine, and in chronic compared to episodic migraine. AMURA can provide additional results with respect to DTI to uncover white matter alterations in migraine.}, issn = {2076-3425}, doi = {10.3390/brainsci10100711}, url = {https://www.mdpi.com/2076-3425/10/10/711}, author = {{\'A}lvaro Planchuelo-G{\'o}mez and Garc{\'\i}a-Azor{\'\i}n, David and {\'A}ngel L. Guerrero and Rodrigo de Luis-Garc{\'\i}a and Rodr{\'\i}guez, Margarita and Santiago Aja-Fern{\'a}ndez} } @article {892, title = {Gray Matter Structural Alterations in Chronic and Episodic Migraine: A Morphometric Magnetic Resonance Imaging Study}, journal = {Pain Medicine}, volume = {21}, year = {2020}, pages = {2997-3011}, abstract = {

This study evaluates different parameters describing the gray matter structure to analyze differences between healthy controls, patients with episodic migraine, and patients with chronic migraine.Cohort study.Spanish community.Fifty-two healthy controls, 57 episodic migraine patients, and 57 chronic migraine patients were included in the study and underwent T1-weighted magnetic resonance imaging acquisition.Eighty-four cortical and subcortical gray matter regions were extracted, and gray matter volume, cortical curvature, thickness, and surface area values were computed (where applicable). Correlation analysis between clinical features and structural parameters was performed.Statistically significant differences were found between all three groups, generally consisting of increases in cortical curvature and decreases in gray matter volume, cortical thickness, and surface area in migraineurs with respect to healthy controls. Furthermore, differences were also found between chronic and episodic migraine. Significant correlations were found between duration of migraine history and several structural parameters.Migraine is associated with structural alterations in widespread gray matter regions of the brain. Moreover, the results suggest that the pattern of differences between healthy controls and episodic migraine patients is qualitatively different from that occurring between episodic and chronic migraine patients.

}, issn = {1526-2375}, doi = {10.1093/pm/pnaa271}, url = {https://doi.org/10.1093/pm/pnaa271}, author = {{\'A}lvaro Planchuelo-G{\'o}mez and Garc{\'\i}a-Azor{\'\i}n, David and {\'A}ngel L. Guerrero and Rodr{\'\i}guez, Margarita and Santiago Aja-Fern{\'a}ndez and Rodrigo de Luis-Garc{\'\i}a} } @article {826, title = {Structural connectivity alterations in chronic and episodic migraine: A diffusion magnetic resonance imaging connectomics study}, journal = {Cephalalgia}, volume = {40}, year = {2020}, pages = {367-383}, abstract = {

OBJECTIVE:

To identify possible structural connectivity alterations in patients with episodic and chronic migraine using magnetic resonance imaging data.

METHODS:

Fifty-four episodic migraine, 56 chronic migraine patients and 50 controls underwent T1-weighted and diffusion-weighted magnetic resonance imaging acquisitions. Number of streamlines (trajectories of estimated fiber-tracts), mean fractional anisotropy, axial diffusivity and radial diffusivity were the connectome measures. Correlation analysis between connectome measures and duration and frequency of migraine was performed.

RESULTS:

Higher and lower number of streamlines were found in connections involving regions like the superior frontal gyrus when comparing episodic and chronic migraineurs with controls (p \< .05 false discovery rate). Between the left caudal anterior cingulate and right superior frontal gyri, more streamlines were found in chronic compared to episodic migraine. Higher and lower fractional anisotropy, axial diffusivity, and radial diffusivity were found between migraine groups and controls in connections involving regions like the hippocampus. Lower radial diffusivity and axial diffusivity were found in chronic compared to episodic migraine in connections involving regions like the putamen. In chronic migraine, duration of migraine was positively correlated with fractional anisotropy and axial diffusivity.

CONCLUSIONS:

Structural strengthening of connections involving subcortical regions associated with pain processing and weakening in connections involving cortical regions associated with hyperexcitability may coexist in migraine

}, keywords = {Magnetic resonance imaging (MRI), Migraine, chronic migraine, connectomics, diffusion-weighted imaging, tractography}, doi = {10.1177/0333102419885392}, author = {{\'A}lvaro Planchuelo-G{\'o}mez and Garc{\'\i}a-Azor{\'\i}n, David and {\'A}ngel L. Guerrero and Santiago Aja-Fern{\'a}ndez and Rodr{\'\i}guez, Margarita and Rodrigo de Luis-Garc{\'\i}a} } @article {837, title = {White matter changes in chronic and episodic migraine: a diffusion tensor imaging study}, journal = {The Journal of Headache and Pain}, volume = {21}, year = {2020}, pages = {1}, chapter = {1}, abstract = {

BACKGROUND:

White matter alterations have been observed in patients with migraine. However, no microstructural white matter alterations have been found particularly in episodic or chronic migraine patients, and there is limited research focused on the comparison between these two groups of migraine patients.

METHODS:

Fifty-one healthy controls, 55 episodic migraine patients and 57 chronic migraine patients were recruited and underwent brain T1-weighted and diffusion-weighted MRI acquisition. Using Tract-Based Spatial Statistics (TBSS), fractional anisotropy, mean diffusivity, radial diffusivity and axial diffusivity were compared between the different groups. On the one hand, all migraine patients were compared against healthy controls. On the other hand, patients from each migraine group were compared between them and also against healthy controls. Correlation analysis between clinical features (duration of migraine in years, time from onset of chronic migraine in months, where applicable, and headache and migraine frequency, where applicable) and Diffusion Tensor Imaging measures was performed.

RESULTS:

Fifty healthy controls, 54 episodic migraine and 56 chronic migraine patients were finally included in the analysis. Significant decreased axial diffusivity (p \< .05 false discovery rate and by number of contrasts corrected) was found in chronic migraine compared to episodic migraine in 38 white matter regions from the Johns Hopkins University ICBM-DTI-81 White-Matter Atlas. Significant positive correlation was found between time from onset of chronic migraine and mean fractional anisotropy in the bilateral external capsule, and negative correlation between time from onset of chronic migraine and mean radial diffusivity in the bilateral external capsule.

CONCLUSIONS:

These findings suggest global white matter structural differences between episodic migraine and chronic migraine. Patients with chronic migraine could present axonal integrity impairment in the first months of chronic migraine with respect to episodic migraine patients. White matter changes after the onset of chronic migraine might reflect a set of maladaptive plastic changes.

}, keywords = {Diffusion tensor imaging, Magnetic resonance imaging (MRI), Migraine, Tract-based spatial statistics, chronic migraine}, doi = {10.1186/s10194-019-1071-3}, url = {https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-019-1071-3}, author = {{\'A}lvaro Planchuelo-G{\'o}mez and Garc{\'\i}a-Azor{\'\i}n, David and {\'A}ngel L. Guerrero and Santiago Aja-Fern{\'a}ndez and Rodr{\'\i}guez, Margarita and Rodrigo de Luis-Garc{\'\i}a} } @conference {821, title = {White Matter Alterations in Chronic Migraine: A Diffusion Tensor Imaging and Structural Connectivity Study}, booktitle = {19th International Headache Congress International Headache Society}, year = {2019}, month = {2019}, publisher = {Cephalalgia}, organization = {Cephalalgia}, address = {Dublin, Ireland}, abstract = {

Objective: White matter alterations have been observed in patients with migraine. However, no microstructural white matter alterations have been found particularly in Episodic Migraine (EM) with respect to Chronic Migraine (CM) patients. In this study, we investigated whether there are significant differences between EM and CM, and between these groups and healthy controls, using diffusion Magnetic Resonance Imaging (dMRI) data.
Methods: We acquired high-resolution 3D brain T1-weighted and dMRI from 51 Healthy Controls (HC), 55 EM patients and 57 CM patients. Using Tract-Based Spatial Statistics, we compared Fractional Anisotropy (FA), Mean Diffusivity (MD), Radial Diffusivity (RD) and Axial Diffusivity (AD) between the different groups. We also obtained structural connectome matrices for each subject employing both dMRI and T1-weighted acquisitions. Number of streamlines, mean FA and mean AD for each white matter connection were compared between the three groups.
Results: Significant decreased AD (p \<.05 Family Wise Error corrected and volume \>30 mm3) were found in CM compared to EM in 38 white matter regions. Significant differences in the number of streamlines were found in 18 connections from the connectome when comparing migraine patients with healthy controls (p \<.05 False Discovery Rate corrected); significant differences were also found between CM and EM in one of these connections. Furthermore, significant differences in FA and AD were found in three and four connections from the connectome respectively (p \<.05 False Discovery Rate corrected); significant differences were also found between CM and EM in two of AD connections.
Conclusion: Our findings suggest global white matter structural differences between EM and CM, and structural connectivity alterations in migraine patients with respect to healthy controls, and in CM compared to EM.
Disclosure of Interest: None Declared.

}, doi = {https://doi.org/10.1177/0333102419859835}, url = {https://journals.sagepub.com/doi/full/10.1177/0333102419859835}, author = {{\'A}lvaro Planchuelo-G{\'o}mez and Garc{\'\i}a-Azor{\'\i}n, David and {\'A}ngel L. Guerrero and Santiago Aja-Fern{\'a}ndez and Rodr{\'\i}guez, Margarita and Rodrigo de Luis-Garc{\'\i}a} }