Biomedical subjects

Maria A Rocca

Publications and source records attributed to Maria A Rocca.

32 records · Page 2Linked to original sources

PubMed2004

Pyramidal tract lesions and movement-associated cortical recruitment in patients with MS.

Cortical functional changes, with the potential to limit the functional consequences of tissue injury, have been shown in patients with multiple sclerosis (MS). In this study, we assessed the influence of MS-related tissue damage of the brain portion of the left pyramidal tract on the corresponding movement-associated patterns of cortical recruitment in a large sample of MS patients when performing a simple motor task with their fully normal functioning right upper limbs. We investigated 76 right-handed patients with definite MS. In each subject, functional magnetic resonance imaging (fMRI) was acquired during the performance of a simple motor task with the dominant, right upper limb. During the same session, dual-echo, magnetization transfer (MT) and diffusion tensor (DT) MRI sequences were also obtained to quantify the extent and the severity of pyramidal tract damage. Lesions along the left pyramidal tract were identified in 43 patients. Compared to patients without pyramidal tract lesions, patients with such lesions had more significant activations of the contralateral primary sensorimotor cortex (SMC), secondary sensorimotor cortex (SII), inferior central sulcus, and cingulate motor area (CMA). They also showed more significant activations of several regions of the ipsilateral hemisphere, including the primary SMC and the precuneus. In these patients, T2 lesion load of left pyramidal tract was correlated with the extent of activation of the contralateral primary SMC (r2 = 0.25, P < 0.0001), whereas no correlations were found between the extent of fMRI activations and the severity of intrinsic lesion damage, as well as with left pyramidal tract normal-appearing white matter damage. This study shows that, in patients with MS, following injury of the motor pathways, there is an increased recruitment of a widespread sensorimotor network, which is likely to contribute to limit the appearance of overt clinical deficits.

Adult↗

PubMed2004

Magnetization transfer magnetic resonance imaging in the assessment of neurological diseases.

In several white matter diseases of the central nervous system (CNS), and in particular in multiple sclerosis, conventional magnetic resonance imaging (MRI) has proved to be sensitive for detecting lesions and their changes over time. However, conventional MRI is not able to characterize and quantify the tissue damage within and outside such lesions. Magnetization transfer MRI (MT-MRI) is a quantitative MRI technique with the potential to overcome this limitation and, as a consequence, to provide additional information about the nature and the extent of tissue damage. Metrics derived from MT-MRI can quantify the structural changes occurring within and outside lesions visible on conventional MRI scans. The present review summarizes the major contributions given by MT-MRI to provide an accurate in vivo picture of the heterogeneity of CNS pathology and, ultimately, to improve our ability to monitor the evolution of various neurological conditions.

Central Nervous System Diseases↗

PubMed2004

Imaging primary progressive multiple sclerosis: the contribution of structural, metabolic, and functional MRI techniques.

Patients with primary progressive multiple sclerosis (PPMS) typically experience a progressive disease course from onset, leading to the accumulation of severe neurological disability. This is in contrast with the observation that the burden and activity of lesions on conventional magnetic resonance imaging (MRI) scans of the brain are much lower in patients with PPMS than in those with other less disabling forms of the disease. Studies with structural and functional MRI techniques are providing relevant contributions to the understanding of the mechanisms underlying the accumulation of irreversible neurological deficits in patients with PPMS. The results of these studies underpin that the main factors possibly explaining the clinical/MRI discrepancy observed in patients with PPMS include the presence of a diffuse tissue damage that is beyond the resolution of conventional imaging, the extent of cervical cord damage, and the impairment of the adaptive capacity of the cortex to limit the functional consequences of subcortical pathology.

Central Nervous System↗

PubMed2003

Evidence for cortical functional changes in patients with migraine and white matter abnormalities on conventional and diffusion tensor magnetic resonance imaging.

BACKGROUND: In this study, we used functional MRI (fMRI) to investigate the pattern of cortical activations after a simple motor task in patients with migraine and white matter (WM) abnormalities on conventional MRI scans of the brain. We also investigated whether the extent of brain activations was correlated with WM structural pathology measured using diffusion tensor (DT) MRI. METHODS: From 15 right-handed patients with migraine and 15 sex- and age-matched, right-handed healthy volunteers, we obtained the following: (1) fMRI (repetitive flexion-extension of the last 4 fingers of the right hand), (2) dual-echo turbo spin echo scans, and (3) pulsed-gradient spin-echo echo-planar sequence to calculate DT-MRI maps. fMRI analysis was performed using SPM99 and cluster detection. We measured the volume, the average mean diffusivity (), and the average fractional anisotropy of all lesions seen on the dual-echo scans. histograms of the normal-appearing WM were also produced. RESULTS: Compared with healthy volunteers, migraine patients had a larger relative activation of the contralateral primary sensorimotor cortex (P=0.01) and a rostral displacement of the supplementary motor area (P=0.03). The shapes of the curves reflecting the time course for fMRI signal intensity changes were similar between migraine patients and controls for all of the cortical areas we studied. Compared with healthy subjects, migraine patients had significantly lower histogram peak height of the normal-appearing WM histogram (P=0.02), which was found to be correlated with the extent of displacement of the supplementary motor area (r=-0.80, P<0.001). CONCLUSIONS: This study suggests that functional cortical changes occur in patients with migraine and brain MRI abnormalities and that they might be secondary to the extent of subcortical structural damage.

Adolescent↗

PubMed2003

Occult tissue damage in patients with primary progressive multiple sclerosis is independent of T2-visible lesions--a diffusion tensor MR study.

Although quantitative magnetic resonance (MR) studies have shown that primary progressive multiple sclerosis (PPMS) patients have subtle and diffuse changes of the normal-appearing brain tissue (NABT), the nature of these changes is still poorly understood. The aim of this study was to improve our understanding of the NABT damage in PPMS patients by comparing diffusion tensor magnetic resonance (DT MR) quantities of a large portion of the brain from these patients with those from healthy subjects with and without T2-visible lesions. Dual-echo and DT MR images of the brain were obtained from 20 patients with PPMS, 20 age- and gender-matched healthy volunteers with normal conventional MR scans of the brain, and 20 age-, gender- and T2 lesion volume-matched healthy subjects. Mean diffusivity (MD) and fractional anisotropy (FA) histograms of the NABT were derived from all the individuals. Average lesion MD and FA were calculated in PPMS patients and healthy controls with T2-visible lesions. MD and FA histogram-derived metrics of the NABT from PPMS patients differed significantly from the corresponding quantities from healthy volunteers with no brain T2-visible lesions and from those from healthy volunteers with overt brain MR abnormalities (p values ranging from < 0.0001 to 0.01). Average lesion MD was also significantly higher in PPMS patients than in healthy volunteers with T2-visible lesions (p = 0.03). In PPMS patients, no significant correlation was found between any of the DT MR quantities of NABT damage and a) the T2 lesion volume, b) the average lesion MD, and c) the normalized brain volume. This study shows that in PPMS patients there is a significant microscopic damage of the NABT which is independent of the extent of T2-visible abnormalities. This suggests that Wallerian degeneration of fibers passing through macroscopic abnormalities is not a major factor contributing to diffuse NABT pathology of these patients.

Adult↗

PubMed2003

Demyelination and cortical reorganization: functional MRI data from a case of subacute combined degeneration.

Although it is accepted that functional changes of the cortex can occur in patients with white matter diseases of the brain and might have an adaptive role in limiting the clinical consequences of subcortical injury, the pathological substrates able to elicit such cortical changes are still unknown. This multiparametric magnetic resonance study of a patient with an early diagnosis of subacute combined degeneration suggests that demyelination alone does not necessarily induce adaptive functional changes of the cerebral cortex.

Cerebral Cortex↗

PubMed2003

Evidence for axonal pathology and adaptive cortical reorganization in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis.

Previous work has suggested that functional reorganization of cortical areas might have a role in limiting the clinical impact of axonal pathology in patients with established multiple sclerosis (MS). Since there is evidence for irreversible tissue damage even in patients with early MS, we assessed, using functional MRI (fMRI) and a general search method, the brain pattern of movement-associated cortical activations in patients at presentation with clinically isolated syndromes (CIS) suggestive of MS. To elucidate the role of cortical reorganization in these patients, we also investigated the extent to which the fMRI changes correlated with the extent of overall axonal injury of the brain. From 16 right-handed patients at presentation with CIS and 15 right-handed, age- and sex-matched healthy volunteers, we obtained: (1). fMRI (repetitive flexion-extension of the last four fingers of the right hand), (2). conventional MRI scans, and (3). a new, unlocalized proton MR spectroscopy ((1)HMRS) sequence to measure the concentration of N-acetylaspartate of the whole brain (WBNAA). Compared to controls, patients with CIS had more significant activations of the contralateral primary somatomotor cortex (SMC), secondary somatosensory cortex, and inferior frontal gyrus. They also had significant decreased WBNAA concentration. Relative activation of the contralateral primary SMC was strongly correlated with WBNAA levels (r = -0.78, P < 0.001). This study shows that axonal pathology and functional cortical changes over a rather distributed sensorimotor network occur in patients at presentation with CIS suggestive of MS and that these two aspects of the disease are strictly correlated. This suggests that the increased functional recruitment of the cortex in these patients might have an adaptive role in limiting the clinical impact of irreversible tissue damage.

Adaptation, Physiological↗

PubMed2003

Functional cortical changes in patients with multiple sclerosis and nonspecific findings on conventional magnetic resonance imaging scans of the brain.

Recent functional magnetic resonance imaging (fMRI) work has suggested that cortical reorganisation might have an adaptive role in limiting the clinical impact of multiple sclerosis (MS) structural damage. In this study, we investigated whether, in patients with MS, the presence and extent of structural damage of the normal-appearing brain tissue are associated with the extent of the movement-associated pattern of cortical activations. Using fMRI and a general search method, we assessed the patterns of brain activations associated with simple motor tasks in 12 right-handed patients with clinically definite MS and nonspecific T2-weighted abnormalities on conventional MRI scans of the brain and compared them with those from 12 sex- and age-matched right- handed healthy controls. Also investigated were the extent to which the fMRI changes correlated with normal-appearing white matter and grey matter (GM) pathology, measured using diffusion tensor MRI. When performing the simple motor task with the dominant hand, MS patients had more significant activations of the ipsilateral supplementary motor area (SMA), the ipsilateral superior frontal sulcus, the contralateral superior temporal gyrus, and the thalamus than controls. On the contrary, healthy subjects showed more significant activations of the medial part of the contralateral parieto-occipital fissure and the ipsilateral primary sensorimotor cortex (SMC) than patients with MS. In patients with MS, the relative activation of the ipsilateral SMA was correlated with the peak height (r = -0.88, P < 0.001) and position (r = 0.87, P < 0.001) of the GM mean diffusivity histogram. This study shows that cortical reorganisation occurs over a rather distributed sensorimotor network even in patients with MS and nonspecific abnormalities on conventional brain MRI scans. This suggests that, in patients with MS, an increased recruitment of movement-associated cortical network can be elicited by the presence of normal-appearing tissue pathology, which is independent of macroscopic T2-weighted abnormalities.

Adult↗

PubMed2003

A functional magnetic resonance imaging study of patients with secondary progressive multiple sclerosis.

Although several functional magnetic resonance imaging (fMRI) studies have shown adaptive cortical changes in patients with early multiple sclerosis (MS), the presence of brain plasticity and its role in limiting the functional consequences of brain tissue damage in patients with secondary progressive (SP) MS have not been fully investigated yet. In this study, we assessed the movement-associated brain pattern of cortical activations in patients with SPMS and investigated whether the extent of cortical brain activations is correlated with the extent of brain structural changes. From 13 right-handed SPMS patients and 15 sex- and age-matched healthy volunteers, we obtained: (a) brain dual-echo scans; (b) brain mean diffusivity and fractional anisotropy maps of the normal-appearing white (NAWM) and gray matter (NAGM); (c) fMRI during the performance of simple motor tasks [flexion-extension of the last four fingers of the right hand (task 1) and flexion-extension of the right foot (task 2)]. Compared to healthy volunteers, during task 1 performance, SPMS patients showed more significant activations of the ipsilateral inferior frontal gyrus, middle frontal gyrus, bilaterally, and contralateral intraparietal sulcus. During task 2 performance, SPMS patients had more significant activations of the contralateral primary sensorimotor cortex and thalamus and of the ipsilateral upper bank of sylvian fessure. For both tasks, strong correlations (r values ranging from -0.83 to 0.88) were found between relative activations of cortical areas of the motor network and the severity of structural changes of the NAWM and NAGM. This study demonstrates that cortical plasticity does occur in patients with SPMS and that it might have a role in limiting the clinical impact of MS-related damage. It also suggests that, in these patients, functional abilities are sustained by increased recruitment of highly specialized cortical areas.

Adult↗

PubMed2003

The use of quantitative magnetic-resonance-based techniques to monitor the evolution of multiple sclerosis.

Conventional MRI can improve accuracy in the diagnosis of multiple sclerosis (MS) and monitor the efficacy of experimental treatments. However, conventional MRI provides only gross estimates of the extent and nature of tissue damage associated with this disease. Other quantitative magnetic-resonance-based techniques have the potential to overcome the limitations of conventional MRI and, as a consequence, to improve our understanding of the natural history of MS. Magnetisation-transfer, diffusion-weighted, and functional MRI--as well as proton magnetic-resonance spectroscopy--are helping us to elucidate the mechanisms that underlie injury, repair, and functional adaptation in patients with MS. These techniques are substantially changing our understanding of how MS causes irreversible disability and should be used more extensively in clinical trials and in studies of disease progression.

Brain Mapping↗

PubMed2003

Magnetic resonance-based techniques for the study and management of multiple sclerosis.

Conventional magnetic resonance imaging (cMRI) is widely used for diagnosing multiple sclerosis (MS) and for monitoring its activity and evolution. However, the correlation between cMRI and clinical findings of MS is limited, possibly due to the low pathological specificity of the abnormalities seen on cMRI scans and to the inability of cMRI to quantify the extent of the damage of the normal-appearing tissues. Magnetization transfer and diffusion-weighted MRI can quantify the extent and pathological severity of structural changes occurring within and outside cMRI-visible MS lesions. Proton MR spectroscopy can add information on the biochemical nature of such changes. Finally, functional MRI can provide new insights into the role of cortical adaptive changes in limiting the clinical consequences of MS structural damage. The application of quantitative MR-based techniques is changing dramatically our understanding of how MS causes irreversible disability and there is increasing perception that these methodologies should be more extensively employed in clinical trials to derive innovative information.

Brain↗

PubMed2003

Disturbed function and plasticity in multiple sclerosis as gleaned from functional magnetic resonance imaging.

PURPOSE OF REVIEW: This review is intended to provide an up-to-date summary of the main functional magnetic resonance imaging studies conducted in patients with multiple sclerosis, and to show how such studies are changing our views on the ability of the multiple sclerosis brain to limit the clinical consequences of irreversible structural tissue damage. RECENT FINDINGS: Brain cortical reorganization is a common phenomenon occurring in patients with multiple sclerosis, independent of disease duration and clinical phenotype, which can be elicited by macroscopic lesions, as well as by the presence of 'occult' multiple sclerosis-related damage of the brain and cervical cord. An increased recruitment of the cerebral networks involved in the performance of given tasks might represent a first step in cortical reorganization with the potential to maintain a normal level of function in the course of multiple sclerosis. The progressive failure of these mechanisms, because of accumulating tissue damage, might, on the one hand, result in the activation of previously silent 'second-order' compensatory areas, and, on the other, contribute to the accumulation of irreversible disability. SUMMARY: Functional magnetic resonance imaging has the potential to provide important information about cortical reorganization following multiple sclerosis-related tissue damage, which should improve our understanding of the factors associated with the accumulation of irreversible disability in this disease. The enhancement of any beneficial effects of this cortical adaptive plasticity should be considered as a potential target of therapy for multiple sclerosis.

Cerebral Cortex↗

PubMed2002

Adaptive functional changes in the cerebral cortex of patients with nondisabling multiple sclerosis correlate with the extent of brain structural damage.

In multiple sclerosis, the mechanisms underlying the accumulation of disability are poorly understood. Recently, it has been suggested that adaptive cortical changes may limit the clinical impact of multiple sclerosis injury. In this study, functional magnetic resonance imaging and a general search method were used to assess patterns of brain activation associated with a simple motor task in 14 right-handed, nondisabled relapsing-remitting multiple sclerosis patients that were compared to those from 15 right-handed, sex- and age-matched healthy volunteers. Also investigated were the extent to which the functional magnetic resonance imaging changes correlated with T2 lesion volume and severity of multiple sclerosis pathology in lesions and normal-appearing brain tissue, measured using magnetisation transfer and diffusion tensor magnetic resonance imaging. Compared to controls, multiple sclerosis patients showed increased activation in the contralateral primary sensorimotor cortex, bilaterally in the supplementary motor area, bilaterally in the cingulate motor area, in the contralateral ascending bank of the sylvian fissure, and in the contralateral intraparietal sulcus. T2 lesion volume was correlated with relative activation in the ipsilateral supplementary motor area, and in the ipsilateral and contralateral cingulate motor area. Average lesion magnetisaiton transfer ratio and average lesion water diffusivity were correlated with relative activation in the contralateral sensorimotor cortex. Average lesion magnetisation transfer ratio was also correlated with relative activation in the ipsilateral cingulate motor area. Average water diffusivity and peak height of the normal-appearing brain tissue diffusivity histogram were both correlated with relative activation in the contralateral intraparietal sulcus. This study shows that cortical activation occurs over a rather distributed sensorimotor network in nondisabled relapsing-remitting multiple sclerosis patients. It also suggests that increased recruitment of this cortical network contributes to the limitation of the functional impact of white matter multiple sclerosis injury.

Adaptation, Physiological↗

PubMed2002

Clinical trials and clinical practice in multiple sclerosis: conventional and emerging magnetic resonance imaging technologies.

Conventional magnetic resonance imaging (cMRI) is widely used for diagnosing multiple sclerosis (MS) and as a paraclinical tool to monitor disease activity and evolution in natural history studies and clinical trials. However, the correlation between cMRI and clinical findings is far from strict, and such a discrepancy is even more evident when moving from the setting of large-scale studies to the management of individual patients. Among the reasons for this "clinical-MRI paradox" is the limited specificity of cMRI to the heterogeneous pathologic substrates of MS and its inability to quantify the extent of damage in the normal-appearing tissues. Modern quantitative MR techniques have the potential to overcome some of the limitations of cMRI. Although the application of modern MR techniques is changing dramatically our understanding of how MS causes irreversible disability, their use for clinical trial monitoring and clinical practice is still very limited. Whereas there is increasing perception that modern quantitative MR techniques should be more extensively employed in clinical trials to advance the understanding of MS and derive innovative information, their use in clinical practice should still be regarded as premature.

Central Nervous System↗