Roberta Messina

Influence of the topography of brain damage on depression and fatigue in patients with multiple sclerosis

Objectives: Involvement of selected central nervous system (CNS) regions has been associated with depression and fatigue in MS. We assessed whether specific regional patterns of lesion distribution and atrophy of the gray (GM) and white matter (WM) are associated with these symptoms in MS. Methods: Brain dual-echo and 3D T1-weighted images were acquired from 123 MS patients (69 depressed (D), 54 non-depressed (nD), 64 fatigued, 59 non-fatigued) and 90 controls. Lesion distribution, GM and WM atrophy were estimated using VBM and SPM8. Results: Gender, age, disease duration and conventional MRI characteristics did not differ between D-MS and nD-MS patients. Fatigued patients experienced higher EDSS and depression than non-fatigued ones. Lesion distribution and WM atrophy were not related to depression and fatigue. Atrophy of regions in the frontal, parietal and occipital lobes had a combined effect on depression and fatigue. Atrophy of the left middle frontal gyrus and right inferior frontal gyrus were selectively related to depression. No specific pattern of GM atrophy was found to be related to fatigue. Conclusions: Depression in MS is linked to atrophy of cortical regions located in the bilateral frontal lobes. A distributed pattern of GM atrophy contributes to the concomitant presence of depression and fatigue in these patients.

Regional Cervical Cord Atrophy and Disability in Multiple Sclerosis: A Voxel-based Analysis

PURPOSE To (a) apply an active surface method to map the regional distribution of cord atrophy across levels and sectors in a relatively large group of patients with multiple sclerosis (MS), (b) compare the anatomic location of cord atrophy between patients with relapsing-remitting (RR) MS and those with secondary progressive (SP) MS, and (c) assess correlations between atrophy and disability. MATERIALS AND METHODS This study was approved by the local ethical committee, and written informed consent was obtained from each participant. High-spatial-resolution magnetic resonance (MR) images of the cervical cord were acquired from 45 patients with RR MS, 26 patients with SP MS, and 67 age-matched healthy control subjects. The active surface method segmented the cord surface from C1 to C7 and created output images reformatted in planes perpendicular to the estimated cord center line. These unfolded cervical cord images were coregistered into a common standard space, and smoothed cord binary masks were used as input images for spatial statistics. Voxel-wise between-group comparisons and the correlation between regional cord atrophy versus clinical and conventional MR imaging variables were assessed with software. RESULTS Compared with control subjects, patients with RR MS showed localized clusters of atrophy in the posterior cord. Conversely, patients with SP MS showed a widespread pattern of cord atrophy, predominantly in the posterior and lateral cord columns. In patients with MS, cervical cord atrophy was correlated with clinical disability, disease duration, and, to a lesser extent, conventional MR imaging measures of brain injury. No correlation was found between cord atrophy and the presence of focal cord lesions. CONCLUSION Voxel-wise assessment of the regional distribution of damage in the cervical cord is feasible and might improve our understanding of the mechanisms related to the development of irreversible clinical disability in MS.

Multiple sclerosis imaging: recent advances

In this review, we summarize advances in knowledge derived from the application of magnetic resonance imaging (MRI)-based techniques to patients with multiple sclerosis (MS) published in the Journal of Neurology over the past year. We highlight the pivotal role played by conventional MRI techniques for a correct and early diagnosis of this condition and the exclusion of alternative disorders. Advanced MR methods have contributed to demonstrating how damage to selected brain structures is related to disease clinical manifestations, thus contributing to overcome the well-known “clinical-radiological” paradox of MS, and ameliorating the understanding of the mechanisms underlying the accumulation of irreversible disability. Finally, we discuss the use of MRI to assess treatment efficacy and optimize therapeutic approaches in this condition.

White matter microstructure abnormalities in pediatric migraine patients

Background Diffusion tensor (DT) magnetic resonance imaging (MRI) provides several quantities with the potential to disclose white matter (WM) microstructural abnormalities. We explored alterations of WM architecture in pediatric migraine patients using DT MRI and two different methods of analysis. Methods Dual-echo and DT MRI scans were acquired from 15 pediatric migraine patients and 15 age-matched controls. Whole-brain voxel-wise comparisons of WM DT MRI abnormalities were performed using tract-based-spatial-statistics (TBSS). A DT probabilistic tractography analysis was also run. Results Both TBSS and DT tractography analysis showed that, compared to controls, pediatric migraine patients had significant lower mean (MD), axial (AD) and radial (RD) diffusivity of WM tracts located in the brainstem, thalamus and fronto-temporo-occipital lobes, bilaterally. Patients also experienced increased fractional anisotropy (FA) of the optic radiations. No correlation was found between WM tract abnormalities and disease duration and attack frequency. Conclusions Pediatric migraine patients harbor diffuse brain WM microstructural abnormalities. High FA and low MD, AD and RD in these patients might be explained by repeated neuronal activation, which may lead to cell swelling and stimulate activity-dependent myelin-modulation, or by increased fiber and dendritic densities. Both these mechanisms might reflect a hyperexcitability of the brain in migraineurs.

An update on migraine: current understanding and future directions

Migraine is a common brain disorder with high disability rates which involves a series of abnormal neuronal networks, interacting at different levels of the central and peripheral nervous system. An increase in the interest around migraine pathophysiology has allowed researchers to unravel certain neurophysiological mechanisms and neurotransmitter involvement culminating in the recent development of novel therapies, which might substantially change the clinical approach to migraine patients. The present review will highlight the current aspects of migraine pathophysiology, covering an understanding of the complex workings of the migraine state and the brain regions responsible for them. We will further discuss the therapeutic agents which have appeared in the most recent years for migraine care, from calcitonin gene-related peptide (CGRP) receptor antagonists, gepants; through serotonin 5-HT1F receptor agonists, ditans, and CGRP or CGRP receptor monoclonal antibodies to invasive and non-invasive neuromodulation techniques.

Resting-state fMRI functional connectivity: a new perspective to evaluate pain modulation in migraine?

Resting-state (RS) functional magnetic resonance imaging (fMRI) is a relatively novel tool which explores connectivity between functionally linked, but anatomically separated, brain regions. The use of this technique has allowed the identification, at rest, of the main brain functional networks without requiring subjects to perform specific active tasks. Methodologically, several approaches can be applied for the analysis of RS fMRI, including seed-based, independent component analysis-based and/or cluster-based methods. The most consistently described RS network is the so-called “default mode network”. Using RS fMRI, several studies have identified functional connectivity abnormalities in migraine patients, mainly located at the level of the pain-processing network. RS functional connectivity is generally increased in pain-processing network, whereas is decreased in pain modulatory circuits. Significant abnormalities of RS functional connectivity occur also in affective networks, the default mode network and the executive control network. These results provide a strong characterization of migraine as a brain dysfunction affecting intrinsic connectivity of brain networks, possibly reflecting the impact of long lasting pain on brain function.

Estimating Brain Lesion Volume Change in Multiple Sclerosis by Subtraction of Magnetic Resonance Images.

Change in lesion volume over time, measured on brain magnetic resonance imaging (MRI) scans, is an important outcome measure for natural history studies and clinical trials in multiple sclerosis (MS).

Structural brain abnormalities in patients with vestibular migraine

New advances in understanding the pathophysiology of vestibular migraine (VM) have suggested a large overlap between migraine and vestibular pathways. We explored the regional distribution of gray (GM) and white matter (WM) abnormalities in VM patients in comparison to migraine patients with (MWA) and without aura (MWoA) and their correlations with patients’ clinical manifestations. Using a 3.0 Tesla scanner, brain T2-weighted and 3D T1-weighted MRI scans were acquired from 19 VM, 19 MWA, 19 MWoA and 20 age-matched controls. GM and WM volumetric abnormalities were estimated using voxel-based morphometry (SPM12). Compared to controls, migraine patients had decreased GM volume of the left cerebellum and an increased GM volume of the left temporal lobe. VM patients had a selective GM volume increase of frontal and occipital regions compared to controls and the other two groups of migraineurs and no regions with decreased GM volume. Compared to MWoA and MWA, VM had increased GM volume of the left thalamus. Regional GM abnormalities did not correlate with disease duration and attack frequency. No WM volumetric differences were detected between migraine patients and controls. These results show that GM volume abnormalities of nociceptive and multisensory vestibular brain areas occur in VM patients. Overall, our findings suggest that an abnormal brain sensitization might lead to a dismodulation of multimodal sensory integration and processing cortical areas in VM patients.

A review of recent literature on functional MRI and personal experience in two cases of definite vestibular migraine

The pathophysiology of vestibular migraine (VM) is at present poorly understood. Functional magnetic resonance imaging (fMRI), a technique that measures brain activity by detecting changes associated with blood flow oxygenation, has been used to study neural pathways involved in VM pathophysiology. In this study, we summarize results of previous fMRI studies in VM patients, both during and between vertigo attacks. Moreover, we report our experience in two patients with definite VM, who underwent fMRI during a visual stimulation in a vertigo-free period. Compared with 15 matched healthy controls, fMRI demonstrated activation of brain areas related to integration of visual and vestibular cues (increased activation of the paracentral lobule and bilateral inferior parietal lobule and decreased activation of the left superior frontal gyrus, head of the caudate nucleus, left superior temporal gyrus, left parahippocampal gyrus, and right lingual gyrus). Our results partially confirm those of other authors, reporting increased activation of multimodal association brain areas (BA 40, BA 31/5) and decreased activation of occipital regions In addition, we also found a decreased activation of fronto-temporal areas, such as the parahippocampal region, functionally involved in space memory and navigation.

Relation between characteristics of carotid atherosclerotic plaques and brain white matter hyperintensities in asymptomatic patients

White matter hyperintensities (WMH) can be incidentally found in patients with carotid atherosclerosis on brain magnetic resonance imaging (MRI). We investigated the relationship between WMH and characteristics of carotid plaques in asymptomatic patients without indication for carotid revascularization. We prospectively screened 235 consecutive patients with carotid stenosis <70%. After excluding patients with confounding causes of cerebral damage, 67 asymptomatic patients underwent carotid computed tomography angiography (CTA), contrast-enhanced ultrasound and brain MRI. Number and quantitative measurement of volume of WMH were associated with history of resistant hypertension, degree of stenosis (Doppler) and presence of an ulcerated plaque at CTA (p < 0.05). At multivariate regression analysis, resistant hypertension was independently associated with both number and volume of WMH, presence of an ulcer with number of WMH and degree of stenosis with WMH volume (p < 0.05), although WMH were equally distributed in both hemispheres irrespectively of plaque side. In conclusion, in asymptomatic patients with carotid plaques <70%, a higher burden of WMHs is associated with history of resistant hypertension that could be the expression of microvascular damage. Stenosis severity and presence of plaque ulceration are also associated with WMH burden although their causative relation is not supported by the bilateral distribution of WMH.