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Massimo Filippi

Publications and source records attributed to Massimo Filippi.

At least 55 records · Page 3Linked to original sources

Clinical trials in multiple sclerosis: methodological issues.

PURPOSE OF REVIEW: The availability of partially effective immunomodulatory and immunosuppressive treatments for relapsing multiple sclerosis (MS) opens important ethical, methodological and practical issues in the design and conduct of new clinical trials in these patients. RECENT FINDINGS: The recommendation of the National Health Authorities to prioritize phase III clinical trials using placebo arm raises ethical questions. In addition, patients are reluctant to be involved in such trials. Alternative clinical trial designs will be discussed. Relapses and active lesions are accepted measures of disease activity; new/enlarging T2 lesions and/or enhancing lesions are accepted surrogate markers of disease activity in phase II clinical trials. On the contrary, there are no accepted magnetic resonance imaging (MRI) surrogate markers of disease progression and also the clinical measures to monitor the degenerative aspects of the disease are not without important limitations. New scales of impairment, disability and quality of life will be reviewed extensively. We will also focus on the value of modern and quantitative MRI techniques, which hold substantial promise as tools to estimate the extent of MS-related irreversible tissue loss. SUMMARY: The use of an active comparator in a superior clinical-trial design is becoming an attractive option for testing the efficacy of new drugs in relapsing MS. At present there are no fully reliable and sensitive clinical markers of the accumulation of irreversible tissue damage in MS. Although additional extensive application in longitudinal studies is needed, modern MRI techniques are promising tools to monitor the neurodegenerative aspects of MS.

Animals↗

Magnetic resonance imaging monitoring of multiple sclerosis lesion evolution.

The characteristic feature of multiple sclerosis (MS) pathology is the demyelinated plaque distributed throughout the central nervous system. Although MS is a primary demyelinating disease, acute axonal injury is common in actively demyelinating MS lesions and it is considered one of the major determinants of neurological deficit. Magnetic resonance imaging (MRI) has had a dramatic impact on MS in both the clinical practice and basic science settings. Techniques such as T2-weighted and gadolinium-enhanced T1-weighted MRI are very sensitive in detecting lesions and, thus, increase the level of certainty of MS diagnosis. Conventional MRI has also improved our understanding of the pathogenesis of the disease and has provided objective and reliable measures to monitor the effect of experimental treatments in clinical trials. However, conventional MRI does not provide specific information on the heterogeneous pathologic substrate of MS lesions. Advanced MRI techniques, such as magnetization transfer imaging, diffusion tensor imaging, and proton MR spectroscopy, offer the unprecedented ability to observe and quantify pathological changes in lesions and normal-appearing brain tissue over time. The present review will discuss the major contributions of conventional MRI and quantitative MRI techniques to understand how individual MS lesions evolve.

Atrophy↗

Glatiramer acetate in multiple sclerosis.

Glatiramer acetate (Copaxone) is a disease-modifying agent approved by several health authorities worldwide for the treatment of relapsing-remitting multiple sclerosis. Although its primary target is the inflammatory component of the disease, there are emerging pieces of evidence suggesting that glatiramer acetate might also have a neuroprotective effect. In this review, the results of glatiramer acetate clinical trials and other relevant studies as well as the place of glatiramer acetate among other approved disease-modifying treatments for relapsing-remitting multiple sclerosis are discussed critically.

Glatiramer Acetate↗

Regional brain atrophy evolves differently in patients with multiple sclerosis according to clinical phenotype.

BACKGROUND AND PURPOSE: Progressive brain atrophy is a well-known feature of multiple sclerosis (MS). We characterized the spatial evolution of atrophy in different MS phenotypes. METHODS: Dual-echo and T1-weighted MR images were obtained in 70 patients with MS and 10 healthy control subjects at entry and after 15 months. Within-group changes in regional atrophy were assessed by applying Structural Image Evaluation Using Normalization of Atrophy software and statistical parametric mapping analysis. Reported differences are for P <.001. RESULTS: During follow-up, patients with relapsing-remitting MS (RRMS) differences significant atrophy around the ventricular system; pericerebellar spaces; cerebellar tentorium; putamen; corpus callosum; cingulate sulcus; hippocampus; parieto-occipital fissure; lateral fissure; and frontal, parietal, temporal, and occipital cortex. Patients with secondary progressive MS developed significant atrophy of the cingulate sulcus; pulvinar; caudate nucleus; anterior orbital gyrus; mammillary body; fourth ventricle; and regions of frontal, parietal, temporal, and occipital cortex. Patients with primary progressive MS developed significant atrophy of the bilateral central sulcus; caudate nucleus; prepontine and quadrigeminal cisterns; lateral ventricle; and regions of frontal, parietal, temporal, and occipital cortex. In all phenotypes, the development of atrophy in some regions was significantly correlated with the accumulation of T2- and T1-visible lesions and clinical disability (r = -0.57 to -0.86). CONCLUSION: In MS, brain atrophy develops involving different structures in the different phenotypes. While ventricular enlargement is predominant in RRMS, cortical atrophy seems to be more important in the progressive forms. Measures of regional brain atrophy were significantly correlated with disability, suggesting that this approach is promising for bridging the gap between clinical and MR imaging findings in MS.

Adult↗

Diffusion-weighted MR of the brain: methodology and clinical application.

Clinical diffusion magnetic resonance (MR) imaging in humans started in the last decade with the demonstration of the capabilities of this technique of depicting the anatomy of the white matter fibre tracts in the brain. Two main approaches in terms of reconstruction and evaluation of the images obtained with application of diffusion sensitising gradients to an echo planar imaging sequence are possible. The first approach consists of reconstruction of images in which the effect of white matter anisotropy is averaged -- known as the isotropic or diffusion weighted images, which are usually evaluated subjectively for possible areas of increased or decreased signal, reflecting restricted and facilitated diffusion, respectively. The second approach implies reconstruction of image maps of the apparent diffusion coefficient (ADC), in which the T2 weighting of the echo planar diffusion sequence is cancelled out, and their objective, i.e. numerical, evaluation with regions of interest or histogram analysis. This second approach enables a quantitative and reproducible assessment of the diffusion changes not only in areas exhibiting signal abnormality in conventional MR images but also in areas of normal signal. A further level of image post-processing requires the acquisition of images after application of sensitising gradients along at least 6 different spatial orientations and consists of computation of the diffusion tensor and reconstruction of maps of the mean diffusivity (D) and of the white matter anisotropic properties, usually in terms of fractional anisotropy (FA). Diffusion-weighted imaging is complementary to conventional MR imaging in the evaluation of the acute ischaemic stroke. The combination of diffusion and perfusion MR imaging has the potential of providing all the information necessary for the diagnosis and management of the individual patient with acute ischaemic stroke. Diffusion-weighted MR, in particular quantitative evaluation based on the diffusion tensor, has a fundamental role in the assessment of brain maturation and of white matter diseases in the fetus, in the neonate and in the child. Diffusion MR imaging enables a better characterisation of the lesions demonstrated by conventional MR imaging, for instance in the hypoxic-ischaemic encephalopathy, in infections and in the inherited metabolic diseases, and is particularly important for the longitudinal evaluation of these conditions. Diffusion-weighted MR imaging has an established role in the differential diagnosis between brain abscess and cystic tumour and between epidermoid tumour and arachnoid cyst. On the other hand, the results obtained with diffusion MR in the characterisation of type and extension of glioma do not yet allow decision making in the individual patient. Diffusion is one of the most relevant MR techniques to have contributed to a better understanding of the pathophysiological mechanisms of multiple sclerosis (MS). In fact, it improves the specificity of MR in characterising the different pathological substrata underlying the rather uniform lesion appearance on the conventional images and enables detection of damage in the normal-appearing white and grey matter. In MS patients the ADC or D values in the normal-appearing white matter are increased as compared to control values, albeit to a lesser degree than in the lesions demonstrated by T2-weighted images. In addition, the D of the normal appearing grey matter is increased in MS patients and this change correlates with the cognitive deficit of these patients. Histogram analysis in MS patients shows that the peak of the brain D is decreased and right-shifted, reflecting an increase of its value, and the two features correlate with the patient's clinical disability. Ageing is associated to a mild but significant increase of the brain ADC or D which is predominantly due to changes in the white matter. Region of interest and histogram studies have demonstrated that D or ADC are increased in either the areas of leukoaraiosis or the normal-appearing white matter in patients with inherited cerebral autosomal dominant arteriopathy with subcortical infarcts and stroke or sporadic ischaemic leukoencephalopathy. Diffusion changes might be a more sensitive marker for progression of the disease than conventional imaging findings. In neurodegenerative diseases of the central nervous system such as Alzheimer's disease, Huntington's disease, hereditary ataxias and motor neuron disease, quantitative diffusion MR demonstrates the cortical and subcortical grey matter damage, which is reflected in a regional increase of D or ADC, but also reveals the concomitant white matter changes that are associated with an increase in D or ADC and decrease in FA. In all these diseases the diffusion changes are correlated to the clinical deficit and are potentially useful for early diagnosis and longitudinal evaluation, especially in the context of pharmacological trials.

Brain Diseases↗

Persistence of congenital mirror movements after hemiplegic stroke.

We describe a case of hereditary congenital mirror movements (MMs) in a 76-year-old man, who after an ischemic stroke, had persistence of MMs in the paretic hand during voluntary movements of the contralateral arm. By using functional MR imaging to investigate the performance of motor and sensory tasks with the affected and the unaffected hands, we found evidence for increased ipsilateral primary motor cortex activity and reduced transcallosal inhibition. Both these mechanisms are likely to be involved in the genesis of MMs.

Aged↗

A widespread pattern of cortical activations in patients at presentation with clinically isolated symptoms is associated with evolution to definite multiple sclerosis.

BACKGROUND AND PURPOSE: Movement-associated cortical changes have been detected at the earlier clinical stage multiple sclerosis. Our purpose was to assess whether different patterns of cortical recruitment are associated with the short-term evolution of definite multiple sclerosis (MS). METHODS: We followed for 1 year a group of patients with clinically isolated syndromes (CISs) suggestive of MS and compared the baseline movement-associated patterns of cortical activations between those patients with and those without evolution to definite MS. RESULTS: Those patients in whom MS did not evolve had more significant activations of several areas part of the "classic" motor network; those who went on to develop MS had more significant activations of several regions in the frontal, parietal, temporal, and occipital lobes. CONCLUSION: In CIS patients, the extent of early cortical reorganization following tissue injury might be a factor associated with a different disease evolution.

Adult↗

Short-term accrual of gray matter pathology in patients with progressive multiple sclerosis: an in vivo study using diffusion tensor MRI.

The mechanisms underlying the progressive course of multiple sclerosis (MS) are not fully understood yet. Since diffusion tensor (DT) MRI can provide quantitative estimates of both MRI-visible and MRI-occult brain damage related to MS, the present study investigated the value of DT MRI-derived measures for the assessment of the short-term accumulation of white and gray matter (GM) pathology in patients with primary progressive (PP) and secondary progressive (SP) MS. Fifty-four patients with PPMS and 22 with SPMS were studied at baseline and after a mean follow-up of 15 months. Dual-echo, T1-weighted, and DT MRI scans of the brain were acquired on both occasions. Total lesion volumes (TLV) and percentage brain volume changes (PBVC) were computed. Mean diffusivity (MD) and fractional anisotropy (FA) maps of the normal-appearing white (NAWM) and gray matter (NAGM) were produced, and histogram analysis was performed. In both patient groups, a significant increase of average lesion MD (P = 0.01) and of average NAGM MD (P = 0.007) was found at follow-up. No significant differences between PPMS and SPMS patient groups were found for the on-study changes of any MRI-derived measure. No significant correlations were found between the percentage changes of DT MRI-derived measures and those of TLV and PBVC. No significant changes of DT MRI-derived measures were observed in age-matched healthy controls over the same study period. Over a 1-year period of follow-up, DT MRI can detect tissue changes beyond the resolution of conventional MRI in the NAGM of patients with progressive MS. The accumulation of DT MRI-detectable gray matter damage does not seem to merely depend upon the concomitant increase of T2-visible lesion load and the reduction of brain volume. These observations suggest that progressive NAGM damage might yet be an additional factor leading to the accumulation of disability in progressive MS.

Adult↗

Autologous HSCT for severe progressive multiple sclerosis in a multicenter trial: impact on disease activity and quality of life.

Hematopoietic stem cell transplantation (HSCT) has been proposed for the treatment of severe multiple sclerosis (MS). In a phase 2 multicenter study we selected 19 non-primary progressive MS patients showing high disease activity on the basis of both brain magnetic resonance imaging (MRI) and sustained clinical deterioration despite conventional treatments. After stem cell mobilization with cyclophosphamide (CY) and filgrastim, patients were conditioned with BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea), cytosine arabinoside, etoposide, and melphalan (BEAM) followed by antithymocyte globulin (ATG). Unmanipulated peripheral blood stem cells (PBSCs) were then infused. No maintenance treatment was administered with a median follow-up of 36 months (range, 12 to 72 months). All patients showed clinical stabilization or improvement; 3 subsequently deteriorated, 1 beyond the baseline. No MRI active lesions were detected after the HSCT except in 1 patient who showed a new lesion at 4.5 years. Infections were limited and restricted to 3 months after HSCT. Health-related quality of life was assessed through the 54-item MS quality of life (MSQOL-54) questionnaire, showing a statistically significant improvement in both composite scores and in most of the individual domains. HSCT is able to induce a prolonged clinical stabilization in severe progressive MS patients, resulting in both sustained treatment-free periods and quality of life improvement.

Adult↗

Huntington disease: volumetric, diffusion-weighted, and magnetization transfer MR imaging of brain.

PURPOSE: To investigate whether diffusion-weighted and magnetization transfer (MT) magnetic resonance (MR) imaging depict regional and/or global brain abnormalities in patients with Huntington disease (HD). MATERIALS AND METHODS: Twenty-one carriers of the HD mutation (mean age, 58 years +/- 11 [SD]) and 21 healthy control subjects (mean age, 54 years +/- 13) underwent conventional, diffusion-weighted, and MT MR imaging. Volumes, mean apparent diffusion coefficients (ADCs), and MT ratios (MTRs) for left and right caudate nucleus, putamen, and cerebral periventricular white matter-as well as an index of normalized brain volume and whole-brain ADC and MT histograms-were computed. Asymmetry in volume, ADC, and MTR measurements in caudate nucleus, putamen, and periventricular white matter in control subjects and HD carriers were evaluated with Wilcoxon testing for paired samples. Differences in MR imaging variables between HD carriers and control subjects were evaluated with Mann-Whitney U testing; correlations between stages of clinical severity and MR imaging data were investigated with Spearman rank correlation testing. RESULTS: No significant asymmetry was observed for any of the MR imaging variables. Caudate nucleus, putamen, and whole-brain volumes were smaller (P <.001 for all) in HD carriers than in control subjects. HD carriers also had increased ADC in the caudate nucleus (P =.002), putamen (P <. 001), cerebral periventricular white matter (P <.001), and whole brain (P <.001). MTR was not significantly different between HD carriers and control subjects. Correlation was observed between stages of increasing clinical disease severity and both decrease in volume of caudate nucleus (Spearman rho = -0.63), putamen (rho = -0.64), and whole brain (rho = -0.46) and increase in ADC in caudate nucleus (rho = 0.52), periventricular white matter (rho = 0.45), and whole brain (rho = 0.44). CONCLUSION: Regional and global volume loss in HD is accompanied by an increase in ADC; this correlates with disease severity.

Adult↗

A preliminary diffusion tensor and magnetization transfer magnetic resonance imaging study of early-onset multiple sclerosis.

BACKGROUND: Early-onset multiple sclerosis (MS) typically has a more favorable course than adult-onset disease. OBJECTIVE: To assess the extent of microscopic tissue damage in the brain and cervical cord of patients with early-onset MS. DESIGN: During a single magnetic resonance imaging session, images of the brain and spinal cord were obtained using diffusion tensor and magnetization transfer magnetic resonance imaging. PATIENTS: We studied 13 patients with early-onset MS and 10 healthy volunteers. RESULTS: Compared with control subjects, patients with early-onset MS showed only a slight increase of the average mean diffusivity of the normal-appearing brain tissue. CONCLUSION: The relatively modest central nervous system damage detected in these patients might explain why early-onset MS typically has a more favorable clinical course than adult-onset MS.

Adolescent↗

European study on intravenous immunoglobulin in multiple sclerosis: results of magnetization transfer magnetic resonance imaging analysis.

BACKGROUND: Magnetization transfer magnetic resonance imaging (MT MRI) can provide in vivo markers reflecting the severity of multiple sclerosis-related brain damage occurring within and outside T2-visible lesions. OBJECTIVE: To investigate the effect of intravenous immunoglobulin (IVIG) treatment on the accumulation of brain damage in patients with secondary progressive multiple sclerosis (SPMS), measured using MT MRI.Design, Patients, and Intervention Seventy patients with SPMS participating in the European, multicenter, randomized, double-blind, placebo-controlled trial of IVIG in SPMS underwent brain T2-weighted and MT MRI at baseline and after 12 and 24 months. The MT MRI scans were post-processed and analyzed to obtain MT ratio values from T2-visible lesions and MT ratio histograms from the normal-appearing brain tissue (NABT). RESULTS: At baseline, a significant difference was found for NABT MT ratio histogram peak height (P =.003) between treated patients and patients receiving placebo. No significant differences between treated patients and those receiving placebo were found for any of the considered MT MRI-derived metrics in terms of treatment x time interaction. Nevertheless, over the 24-month period, the placebo patients experienced a 6.75% reduction of the NABT MT ratio histogram peak height, whereas treated patients experienced only a 0.92% reduction of the NABT MT ratio histogram peak height. CONCLUSIONS: This study did not show any statistically significant effect of IVIG on MT MRI quantities. Nevertheless, the markedly different percentage change of the NABT MT ratio histogram peak height over time between patients receiving placebo and treated patients suggests a possible role of IVIG treatment in preventing the loss of "truly" normal brain tissue in SPMS patients.

Brain↗

Simple and complex movement-associated functional MRI changes in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis.

Using functional magnetic resonance imaging (fMRI), we investigated whether movement-associated functional changes of the brain are present in patients who are, most likely, at the earliest stage of multiple sclerosis (MS). Functional MRI exams were obtained from 16 patients at presentation with clinically isolated syndromes (CIS) suggestive of MS and 15 sex- and age-matched healthy volunteers during the performance of three simple and one more complex motor tasks with fully normal functioning extremities. fMRI analysis was performed using statistical parametric mapping (SPM99). Compared to healthy volunteers, CIS patients had increased activations of the contralateral primary sensorimotor cortex (SMC), secondary somatosensory cortex (SII), and inferior frontal gyrus (IFG), when performing a simple motor task with the dominant hand. The increased recruitment of the contralateral primary SMC was also found during the performance of the same motor task with the non-dominant hand and with the dominant foot. In this latter case, an anterior shift of the center of activation of this region was detected. During the performance of a complex motor task with the dominant upper and lower limbs, CIS patients had an increased recruitment of a widespread network (including the frontal lobe, the insula, the thalamus), usually considered to function in motor, sensory, and multimodal integration processing. The comparison of brain activations during the performance of simple vs. complex motor tasks showed that the movement-associated somatotopic organization of the cerebral and cerebellar cortices was retained in patients with CIS. Cortical reorganization occurs in patients at presentation with CIS highly suggestive of MS. Local synaptic reorganization, recruitment of parallel existing pathways, and reorganization of distant sites are all likely to contribute to the observed functional changes. Hum. Brain Mapping 21:106-115, 2004.

Adult↗

Clinical characteristics, course and prognosis of relapsing Devic's Neuromyelitis Optica.

OBJECTIVES: To evaluate the clinical characteristics, course and prognosis of Devic's neuromyelitis optica (DNO), to evaluate the prognostic role of demographic and clinical features, to evaluate the current DNO diagnostic criteria. METHODS: Demographic, clinical, CSF and MRI data of patients affected by DNO were collected from fifteen Italian MS centres. Inclusion criteria were: 1) two or more acute episodes of neurological dysfunction indicating involvement of the optic nerve and spinal cord, in a simultaneous or subsequent temporal relationship; 2) no evidence of lesions beyond the optic nerve or the spinal cord; 3) brain MRI at onset negative or non-specific for multiple sclerosis (MS) (white matter lesions < or = 2). Disability was scored by means of Kurtzke's Expanded Disability Status Scale (EDSS). RESULTS: 46 patients with relapsing DNO were included, 37 females and 9 males, with mean age at onset of 40.1 +/- 16.3 years (range 12-77 years). The follow up duration was 8.8 +/- 3.5 years, the mean annualised relapse rate was 1.3 +/- 1.2. After 5, 10 and 15 years EDSS 3.0 was reached respectively by 65%, 82 % and 86% of cases, EDSS 6.0 respectively by 42%, 53 % and 69% of cases, EDSS 10 respectively by 8%, 12% and 23% of cases. The probability of reaching EDSS 3 was statistically correlated with age at onset, interval between the first and 2(nd) attack, and relapse rate. The probability of reaching EDSS 6.0 was correlated with the residual EDSS at onset and to relapse rate. During the follow up, brain white matter lesions appeared in 8 subjects. Spinal cord MRI showed lesions extending across 3 or more segments in 39 subjects, only 1 lesion involving 1 segment in 4 subjects, and was normal in 3 subjects. One or more CSF abnormalities were found at least once in 29/44 patients (65.9 %), the most frequent findings being pleocytosis (38.6 %), oligoclonal bands (34.1 %), high protein level (25 %), and high albumin ratio (20.5 %). CONCLUSIONS: DNO has a poor prognosis in most cases. Compared with MS, DNO patients have a higher age at onset, females are more frequently affected, the course is more severe. Brain and spinal cord MRI permit the differentiation of DNO from MS. CSF supports the probability of DNO if it shows increased cells and proteins.

Adolescent↗

A functional MRI study of cortical activations associated with object manipulation in patients with MS.

Previous functional magnetic resonance imaging (fMRI) studies of simple motor tasks have shown that in patients with multiple sclerosis (MS), there is an increased recruitment of several regions part of a complex sensorimotor network. These studies have suggested that this might be the case because patients tend to activate, when performing a simple motor task, regions that are usually activated in healthy subjects during the performance of more complex tasks due to the presence of subcortical structural damage. In this study, we tested this hypothesis by comparing the patterns of cortical activations during the performance of two tasks with different levels of complexity from 16 MS patients and 16 age- and sex-matched controls. The first task (simple) consisted of flexion-extension of the last four fingers of the right hand, and the second task (complex) consisted of object manipulation. During the simple task, MS patients had, when compared to controls, more significant activations of the supplementary motor area (SMA), secondary sensorimotor area, posterior lobe of the cerebellum, superior parietal gyrus (SPG), and inferior frontal gyrus (IFG). These three latter regions are part of a fronto-parietal circuit, whose activation occurs typically in the contralateral hemisphere of healthy subjects during object manipulation, as shown also by the present study. During the performance of the complex task, MS patients showed an increased bilateral recruitment of several areas of the fronto-parietal circuit associated with object manipulation, as well of several other areas, which were mainly in the frontal lobes. This study confirms that some of the regions that are activated by MS patients during the performance of simple motor tasks are part of more complex pathways, recruited by healthy subjects when more complex and difficult tasks have to be performed.

Adult↗

Indirect evidence for early widespread gray matter involvement in relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) has traditionally been viewed as an inflammatory demyelinating white matter (WM) disease of the central nervous system. However, recent pathology and MRI studies have shown lesions in the gray matter (GM) as well. To ascertain the extent of GM involvement, we obtained with nonlocalizing proton MR spectroscopy the concentration of N-acetylaspartate (NAA), a metabolite found almost exclusively in neuronal cells, T2-lesion loads, and GM and WM fractions in the entire brain of 71 relapsing-remitting (RR) MS patients (51 women, 20 men, 25-55 years old) and 41 healthy controls (27 women, 14 men, 23-55 years old). The average whole-brain NAA (WBNAA) difference between the patients and the controls was -2.9 mM (-22%, P < 0.0001); range: +1.2 to -7.8 mM (+8% to -63%). The patients' median T2 lesion volume was 5.5 (range: 0.140-28) cm(3). GM and WM comprised 50.4 +/- 3.8% and 30.4 +/- 5.0% (mean +/- standard deviation), respectively, of the total brain volume in the patients; 53.8 +/- 3.7% and 35.4 +/- 4.7% in the controls. Because WM and GM constitute approximately 40% and 60% of the brain parenchyma, respectively, and the NAA concentration in the former is 2/3 of the latter, WBNAA loss greater than 40% x 2/3 = 27% cannot be explained in terms of WM (axonal) pathology alone and must include widespread GM (neuronal) deficits. Therefore, the concept of MS, even at its earlier stages, as a WM disease might need to be reexamined.

Adult↗

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↗

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↗