Showing papers by "Maria A. Rocca published in 2010"
TL;DR: The results suggest that a dysfunction of the anterior components of the default-mode network may be among the factors responsible for the accumulation of cognitive deficits in patients with progressive multiple sclerosis.
Abstract: Objective: This study explores default-mode network (DMN) abnormalities in patients with secondary progressive (SP) and primary progressive (PP) multiple sclerosis (MS) and whether such abnormalities correlate with cognitive impairment and damage to selected white matter (WM) fiber bundles, quantified using diffusion tensor (DT) MRI tractography. Methods: Resting state (RS) functional MRI and DT MRI data were acquired from 33 patients with SPMS, 24 patients with PPMS, and 24 controls. Independent component analysis (ICA) was used to identify the DMN. SPM5 was used to assess within- and between-group activations. Results: Between-group differences in DMN activity were found in the left medial prefrontal cortex (mPFC), left precentral gyrus (PcG), and anterior cingulate cortex (ACC). Compared to controls, patients with SPMS had reduced activity in the mPFC ( p = 0.01) and PcG ( p = 0.02), while patients with PPMS had reduced activity in the PcG ( p = 0.008) and the ACC ( p = 0.002). Compared to patients with PPMS, patients with SPMS had increased ACC activity ( p = 0.04). Reduction of RS activity in the ACC was more pronounced in cognitively impaired vs cognitively preserved patients with MS ( p = 0.02). In patients with MS, DMN abnormalities correlated with the PASAT and word list test scores ( r values ranging from 0.35 to 0.45) and DT MRI changes in the corpus callosum and the cingulum ( r values ranging from 0.82 to 0.87). Conclusion: These results suggest that a dysfunction of the anterior components of the default-mode network may be among the factors responsible for the accumulation of cognitive deficits in patients with progressive multiple sclerosis.
301 citations
TL;DR: A new semi-automatic method for segmenting the spinal cord from MR images is presented, based on an active surface (AS) model of the cord surface, with intrinsic smoothness constraints, which confirmed the relevance of the new method in measuring cord atrophy in multiple sclerosis.
250 citations
TL;DR: This review provides a state-of-the-art summary of the main results obtained from the application of conventional and modern magnetic resonance– based techniques to quantify MS-related damage, in terms of macroscopic lesions, as well as involvement of the normal-appearing white matter and gray matter and their association with cognitive impairment.
Abstract: Cognitive impairment affects a large proportion of patients with multiple sclerosis (MS) and has a profound impact on their daily-life activities. Improving the knowledge of the pathophysiology of cognitive impairment in MS and of the mechanisms responsible for its evolution over time might contribute to development of better outcome measures and targets for innovative treatment strategies. Due to their ability to detect MS-related abnormalities, MRI techniques are a valuable tool to achieve these goals. Following an updated overview of the assessment methods and profile of cognitive impairment in patients with MS, this review provides a state-of-the-art summary of the main results obtained from the application of conventional and modern magnetic resonance– based techniques to quantify MS-related damage, in terms of macroscopic lesions, as well as involvement of the normal-appearing white matter and gray matter and their association with cognitive impairment. The possible role of brain cortical reorganization in limiting the clinical consequences of disease-related damage is also discussed. Finally, the utility of the previous techniques to monitor the progression of cognitive deficits over time and the efficacy of possible therapeutic strategies is considered.
174 citations
TL;DR: The accuracy of MRI diagnostic criteria for MS is increased when considering the presence of ICLs on baseline scans from patients at presentation with CIS suggestive of MS.
Abstract: Objective: To generate and validate new MRI diagnostic criteria for multiple sclerosis (MS) taking into account not only white matter lesions but also intracortical lesions (ICLs). Methods: Brain double inversion recovery and brain and cord T2- and postcontrast T1-weighted scans were acquired in a training (80 patients with clinically isolated syndromes [CIS], median follow-up = 55.3 months) and a validation (39 patients with CIS, median follow-up = 28.0 months) sample. In the training sample, regression analysis and Cox proportional hazard model were used to identify MRI variables independently predicting the evolution to clinically definite (CD) MS. The best criterion selected was then validated. The performance of the new and previously available MRI criteria for disease dissemination in space (DIS) and time (DIT) were tested. Results: The final multivariate model showed that ≥1 ICL ( p p = 0.03), and ≥ 1 gadolinium-enhancing or ≥1 spinal cord lesion ( p = 0.004) were independent predictors of CDMS. The presence of at least 2 of these variables was the best DIS criterion in both samples. New ICLs had a poor sensitivity for DIT. The combination of the new DIS criterion with the MAGNIMS criteria for DIT yielded to an accuracy of 81%, which was higher than those of the other available criteria. Conclusions: The accuracy of MRI diagnostic criteria for MS is increased when considering the presence of ICLs on baseline scans from patients at presentation with CIS suggestive of MS. If confirmed by other studies, ICL detection might be considered in future diagnostic algorithms for MS.
157 citations
TL;DR: Thalamic atrophy is correlated with long-term accumulation of disability in patients with multiple sclerosis and white matter lesions are likely to contribute to the loss of tissue seen in the thalamus of patients with MS.
Abstract: Baseline thalamic atrophy, but not a decrease in thalamic magnetization transfer ratio, was significantly correlated with deterioration in the Expanded Disability Status Scale score over an 8-year period.
140 citations
TL;DR: How new MR imaging technology is changing dramatically the authors' understanding of the factors associated with ALS evolution is summarized and the reasons why it should be used more extensively in studies of disease progression, including clinical trials are highlighted.
Abstract: In patients with ALS, conventional MR imaging is frequently noninformative, and its use has been restricted to excluding other conditions that can mimic ALS. Conversely, the extensive application of modern MR imaging-based techniques to the study of ALS has undoubtedly improved our understanding of disease pathophysiology and is likely to have a role in the identification of potential biomarkers of disease progression. This review summarizes how new MR imaging technology is changing dramatically our understanding of the factors associated with ALS evolution and highlights the reasons why it should be used more extensively in studies of disease progression, including clinical trials.
120 citations
TL;DR: The aim of this meeting was to generate a common view on the management of paediatric multiple sclerosis patients, to help standardize treatment and to support clinicians with less experience in this field.
Abstract: About 3-5% of all patients with multiple sclerosis experience the onset of their disease under the age of 16. A significant proportion of paediatric multiple sclerosis patients develop significant cognitive disturbances and persistent physical disability. The high relapse rate and the morbidity in the paediatric multiple sclerosis population has triggered the use of disease-modifying therapies that have been shown to reduce relapse rate, disease progression and cognitive decline in adult patients with multiple sclerosis. Hard evidence for the right treatment and its appropriate timing is scarce in paediatric multiple sclerosis. Nevertheless, expertise in this field has grown thanks to recent open-label trials and experience generated in specialized centres. In spring 2009, a first meeting was held in Rotterdam with clinicians from 11 European countries (one from Canada) that are all active in the management of paediatric multiple sclerosis. One of the aims was to generate a common view on the management of paediatric multiple sclerosis patients. The result of this meeting is presented here to help standardize treatment and to support clinicians with less experience in this field.
102 citations
TL;DR: This study provides Class IV evidence that natalizumab, 300 mg IV once every 28 days, decreased EDSS scores in pediatric patients with MS over a mean treatment period of 15.2 months.
Abstract: Objective: To describe the effect of natalizumab in the treatment of subjects with active multiple sclerosis (MS) treated before the age of 18 years. Methods: Nineteen pediatric subjects with MS (mean age 14.6 ± 2.2 years, mean number of attacks 5.2 ± 1.9 during the pretreatment phase of 27.7 ± 19.7 months, median pretreatment Expanded Disability Status Scale score [EDSS] 2.5, range 1.0–5.0) were treated with natalizumab at the dose of 300 mg every 28 days. After treatment initiation, patients were reassessed clinically every month; brain MRI was performed at baseline and every 6 months. Results: Patients received a median number of 15 infusions (range 6–26). A transient reversible worsening of preexisting symptoms occurred in 1 subject during and following the first infusion. All the patients remained relapse-free during the whole follow-up. The median EDSS decreased from 2.5 to 2.0 at the last visit ( p p = 0.008); 3 patients developed new T2-visible lesions at month 6 scan but the overall number of T2 lesions remained stable during the subsequent follow-up. Transient and mild side effects occurred in 8 patients. Conclusions: Natalizumab was well-tolerated in all subjects. A strong suppression of disease activity was observed in all subjects during the follow-up. Classification of evidence: This study provides Class IV evidence that natalizumab, 300 mg IV once every 28 days, decreased EDSS scores in pediatric patients with MS over a mean treatment period of 15.2 months.
82 citations
TL;DR: The results suggest that empathy toward non conspecifics has different neural representation among individuals with different feeding habits, perhaps reflecting different motivational factors and beliefs.
Abstract: Empathy and affective appraisals for conspecifics are among the hallmarks of social interaction. Using functional MRI, we hypothesized that vegetarians and vegans, who made their feeding choice for ethical reasons, might show brain responses to conditions of suffering involving humans or animals different from omnivores. We recruited 20 omnivore subjects, 19 vegetarians, and 21 vegans. The groups were matched for sex and age. Brain activation was investigated using fMRI and an event-related design during observation of negative affective pictures of human beings and animals (showing mutilations, murdered people, human/animal threat, tortures, wounds, etc.). Participants saw negative-valence scenes related to humans and animals, alternating with natural landscapes. During human negative valence scenes, compared with omnivores, vegetarians and vegans had an increased recruitment of the anterior cingulate cortex (ACC) and inferior frontal gyrus (IFG). More critically, during animal negative valence scenes, they had decreased amygdala activation and increased activation of the lingual gyri, the left cuneus, the posterior cingulate cortex and several areas mainly located in the frontal lobes, including the ACC, the IFG and the middle frontal gyrus. Nonetheless, also substantial differences between vegetarians and vegans have been found responding to negative scenes. Vegetarians showed a selective recruitment of the right inferior parietal lobule during human negative scenes, and a prevailing activation of the ACC during animal negative scenes. Conversely, during animal negative scenes an increased activation of the inferior prefrontal cortex was observed in vegans. These results suggest that empathy toward non conspecifics has different neural representation among individuals with different feeding habits, perhaps reflecting different motivational factors and beliefs.
80 citations
TL;DR: The preservation of brain adaptive properties might explain the favorable medium-term clinical outcome of pediatric MS patients and the progressive recruitment of cortical networks over time in patients with the adult RR forms of the disease, thus possibly contributing to subsequent disease evolution.
Abstract: Our results suggest that age of onset of multiple sclerosis might influence the subsequent short-medium–term disease course caused by a different efficiency of brain mechanisms that are adaptive to the underlying disease-related structural damage.
73 citations
TL;DR: TBM was used to map gray matter volume changes associated with motor learning in young healthy individuals and evaluate if GM changes persist three months after cessation of motor training to assess whether the use of different schemes of motorTraining during the learning phase could lead to volume modifications of specific GM structures.
Abstract: We used tensor-based morphometry (TBM) to: 1) map gray matter (GM) volume changes associated with motor learning in young healthy individuals; 2) evaluate if GM changes persist three months after cessation of motor training; and 3) assess whether the use of different schemes of motor training during the learning phase could lead to volume modifications of specific GM structures. From 31 healthy subjects, motor functional assessment and brain 3D T1-weighted sequence were obtained: before motor training (time 0), at the end of training (two weeks) (time 2), and three months later (time 3). Fifteen subjects (group A) were trained with goal-directed motor sequences, and 16 (group B) with non purposeful motor actions of the right hand. At time 1 vs. time 0, the whole sample of subjects had GM volume increase in regions of the temporo-occipital lobes, inferior parietal lobule (IPL) and middle frontal gyrus, while at time 2 vs. time 1, an increased GM volume in the middle temporal gyrus was seen. At time 1 vs. time 0, compared to group B, group A had a GM volume increase of the hippocampi, while the opposite comparison showed greater GM volume increase in the IPL and insula in group B vs. group A. Motor learning results in structural GM changes of different brain areas which are part of specific neuronal networks and tend to persist after training is stopped. The scheme applied during the learning phase influences the pattern of such structural changes.
TL;DR: In CIS patients, deep GM is not spared, suggesting that iron-related changes and neurodegeneration occurs early, and the magnitude of such damage is only minor and not associated with an increased risk of evolution to CDMS.
Abstract: Gray matter (GM) magnetic resonance imaging (MRI) T2 hypointensity, a putative marker of iron deposition, is a frequent finding in patients with clinically definite (CD) multiple sclerosis (MS). The objective of this study was to assess: (a) how early deep GM T2 hypointensity occurs in MS, by studying patients with clinically isolated syndromes (CIS) suggestive of MS, and (b) whether they contribute to predict subsequent evolution to CDMS. Dual-echo scans using two different acquisition protocols were acquired from 47 CIS patients and 13 healthy controls (HC). Normalized T2-intensity of the basal ganglia and thalamus was quantified. Patients were assessed clinically at the time of MRI acquisition and after three years. During the observation period, 18 patients (38%) evolved to CDMS. At the baseline, only the GM T2-intensity of the left caudate nucleus was significantly reduced in CIS patients in comparison with the HC (p = 0.04). At the baseline, the T2 intensity of the left caudate nucleus was significa...
TL;DR: The presence and topographical distribution of brain grey matter (GM) and white matter (WM) injury in LHON patients using voxel‐based morphometry (VBM) was defined and average peripapillary RNFL thickness was significantly decreased in LHONS patients.
Abstract: Patients with Leber's hereditary optic neuropathy (LHON) have loss of central vision with severe damage of small-caliber fibers of the papillomacular bundle and optic nerve atrophy. The aim of this study was to define the presence and topographical distribution of brain grey matter (GM) and white matter (WM) injury in LHON patients using voxel-based morphometry (VBM). The correlation of such changes with neuro-ophthalmologic findings and measurements of peripapillary retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) was also assessed. Dual-echo and fast-field echo scans were acquired from 12 LHON patients and 12 matched controls. VBM analysis was performed using SPM5 and an ANCOVA model. A complete neuro-ophthalmologic examination, including standardized automated Humphrey perimetry as well as average and temporal peripapillary RNFL thickness measurements were obtained in all the patients. Compared with controls, average peripapillary RNFL thickness was significantly decreased in LHON patients. LHON patients also had significant reduced GM volume in the bilateral primary visual cortex, and reduced WM volume in the optic chiasm, optic tract, and several areas located in the optic radiations (OR), bilaterally. Visual cortex and OR atrophy were significantly correlated with average and temporal peripapillary RNFL thickness (P < 0.001; r values ranging from 0.76 to 0.89). Brain damage in patients with LHON is not limited to the anterior visual pathways, but extends posteriorly to the OR and the primary visual cortex. Such a damage to the posterior parts of the visual pathways may be due either to trans-synaptic degeneration secondary to neuroaxonal damage in the retina and optic nerve or to local mitochondrial dysfunction.
TL;DR: Advances in MR imaging technology and methods of analysis are contributing to ameliorating the detection of focal lesions and to quantifying the extent of “occult” pathology and atrophy, as well as to defining the topographic distribution of such changes in the GM of patients with MS.
Abstract: Recent pathologic and MR imaging studies have challenged the classic view of MS as a chronic inflammatory-demyelinating condition affecting solely the WM of the central nervous system. Indeed, an involvement of the GM has been shown to occur from the early stages of the disease, to progress with time, and to be only moderately correlated with the extent of WM injury. In this review, we summarize how advances in MR imaging technology and methods of analysis are contributing to ameliorating the detection of focal lesions and to quantifying the extent of "occult" pathology and atrophy, as well as to defining the topographic distribution of such changes in the GM of patients with MS. These advances, combined with the imaging of brain reorganization occurring after tissue injury, should ultimately result in an improved understanding and monitoring of MS clinical manifestations and evolution, either natural or modified by treatment.
TL;DR: This study shows that, contrary to what happens in secondary progressive multiple sclerosis, the movement-associated pattern of activations seen in benign multiple sclerosis resembles that of healthy people, and its abnormalities are restricted to the sensorimotor network.
Abstract: Objectives: We investigated motor network function in patients with benign multiple sclerosis (BMS) and contrasted the results with those obtained from patients with secondary progressive multiple sclerosis (SPMS) and healthy controls (HC) to elucidate better the factors associated with a favorable clinical evolution in multiple sclerosis (MS). Methods: Diffusion tensor (DT) and fMRI scans during the performance of a simple motor task were prospectively acquired from 17 patients with BMS, 15 patients with SPMS, and 17 HC. Patients with BMS and SPMS were matched for age, gender, and disease duration. DT MRI histograms of the normal-appearing white matter (NAWM) and gray matter (GM) were derived. fMRI analysis was performed using SPM5 (Wellcome Department of Cognitive Neurology, London, UK). Results: Compared with HC, patients with BMS and SPMS had increased activations of the left primary sensorimotor cortex. Patients with SPMS also showed increased activations of the left secondary sensorimotor cortex, left inferior frontal gyrus (IFG), right hippocampus, and several visual areas. Compared with HC and patients with BMS, patients with SPMS had reduced activations of the left supplementary motor area, left putamen, and right cerebellum. Compared with patients with BMS, patients with SPMS had increased activations of the left IFG and right middle occipital gyrus. In patients with MS, fMRI changes were correlated with T2 lesion volumes and DT MRI changes in the NAWM and GM. Conclusions: This study shows that, contrary to what happens in secondary progressive multiple sclerosis, the movement-associated pattern of activations seen in benign multiple sclerosis resembles that of healthy people, and its abnormalities are restricted to the sensorimotor network. The long-term preservation of brain functional adaptive mechanisms in these patients is likely to contribute to their favorable clinical course.
TL;DR: The objective of this study is to examine whether there is evidence of acute neurotoxicity in patients treated with chemotherapy and to investigate the mechanisms leading to neurotoxicity.
Abstract: Chronic neurotoxicity is a recognized long-term complication following chemotherapy in a range of diseases. Neurotoxicity adversely affects patients' quality of life. The objective of this study is to examine whether there is evidence of acute neurotoxicity.
TL;DR: In CH patients a diffuse abnormality of brain functional connectivity is present, which extends beyond the antinoceptive system, and is significantly correlated with disease duration.
Abstract: Introduction: In this study, we investigated whether abnormalities of the brain resting-state networks (RSNs) occur in patients with episodic cluster headache (CH), outside the attacks of the disea...
TL;DR: It is found that intensive and specific training of attention, information processing and executive functions is significantly effective in ameliorating both neuropsychological treated functions and in reducing depression.
Abstract: Neuropsychological impairment affects 40–65% of multiple sclerosis patients, mainly involving speed in information processing, attention, executive functions and memory. Deterioration occurs over time independently from disability and seems to correlate particularly with magnetic resonance imaging (MRI) atrophy measures. Studies on therapies effective in controlling cognitive impairment are scanty. We found that intensive and specific training of attention, information processing and executive functions is significantly effective in ameliorating both neuropsychological treated functions and in reducing depression. Preliminary functional MRI data suggest that possible neural correlates of this neuropsychological training could be an exercise-induced activation of prefrontal and cingulate cortices.
TL;DR: Cervical cord damage outside focal macroscopic lesions is limited in patients with BMS and secondary progressive MS and the assessment of cord and brain pathology provides complementary information to improve the understanding of disability accumulation in MS.
Abstract: Background: Diffusion tensor (DT) MRI enables quantification of the severity of brain and cervical cord pathology in multiple sclerosis (MS). Objective: To investigate DT MRI patterns of cervical cord damage in patients with benign MS (BMS) and secondary progressive MS (SPMS), in order to achieve a better understanding of the mechanisms underlying the development of irreversible disability in MS. Methods: Conventional and DT MRI scans of the cervical cord and brain were acquired from 40 BMS patients, 28 SPMS patients and 18 healthy individuals. Cervical cord and brain mean diffusivity (MD) and fractional anisotropy (FA) maps were created and average MD and FA were calculated. Cross sectional cord area (CSA) was also computed. Results: 37 (92%) BMS patients and all (100%) SPMS patients had macroscopic cervical cord lesions. Compared with healthy individuals, BMS patients had higher average cord MD while SPMS patients had higher average cord MD, lower average cord FA and lower average CSA. Compared with BMS patients, SPMS patients had lower cord average FA and lower average CSA. In MS patients, Expanded Disability Status Scale (EDSS) was correlated with CSA (r = −0.47, p Conclusions: Cervical cord damage outside focal macroscopic lesions is limited in patients with BMS. The assessment of cord and brain pathology provides complementary information to improve the understanding of disability accumulation in MS.
TL;DR: The results suggest that, as compared with healthy controls, PPMS patients show increased activations and abnormal functional connectivity measures in several areas of the sensorimotor network, correlated with the structural damage to the white matter fiber bundles connecting these regions.
Abstract: We combined functional magnetic resonance imaging (fMRI) and diffusion tensor tractography to investigate the functional and structural substrates of motor network dysfunction in patients with primary progressive multiple sclerosis (PPMS). In 15 right-handed PPMS patients and 15 age-matched healthy controls, we acquired diffusion tensor magnetic resonance imaging and fMRI during the performance of a simple motor task. Tractography was used to calculate diffusion tensor-derived measures of the corpus callosum, the corticospinal tract, the optic radiation, the fronto-occipital fasciculus, and the inferior longitudinal fasciculus. Analyses of fMRI activations and functional connectivity were performed using statistical parametric mapping (cluster threshold of P = 0.001, and extent cluster threshold of 10 voxels for comparison of activations; P < 0.05, family-wise error corrected for functional connectivity). As compared with controls, PPMS patients had more significant activations of the left postcentral gyrus, left secondary sensorimotor area, left parahippocampal gyrus, left cerebellum, right primary sensorimotor cortex (SMC), right basal ganglia, right insula, right cingulum, and cuneus bilaterally. As compared with PPMS patients, controls had increased functional connectivity between the left primary SMC and the ipsilateral inferior frontal gyrus. Conversely, PPMS patients showed increased functional connectivity between the left primary SMC and the right cuneus. Moderate correlations were found between functional activations and damage to the tracts studied (r-values between 0.82 and 0.84; P < 0.001). These results suggest that, as compared with healthy controls, PPMS patients show increased activations and abnormal functional connectivity measures in several areas of the sensorimotor network. Such changes are correlated with the structural damage to the white matter fiber bundles connecting these regions.
TL;DR: In PPMS, an increased recruitment of cognitive-related networks might represent a functional reserve with the potential to limit the severity of cognitive impairment.
Abstract: BACKGROUND AND PURPOSE: Cognitive deficits affect ≤30% of patients with PPMS. We investigated the functional correlates of cognitive network dysfunction in patients with PPMS and their correlation with the extent of structural MR imaging damage. MATERIALS AND METHODS: From 16 right-handed patients with PPMS and 17 matched controls, structural and fMRIs (during the performance of the 2-back task) were acquired. Neuropsychological tests exploring memory, attention, and frontal lobe cognitive domains were administered. T2 LL, NBV, and CC areas were measured. RESULTS: Six patients with PPMS were CI. Structural MR imaging measures did not differ between patients who were CI and those who were CP. Compared with patients who were CI, patients who were CP had increased activations of the left caudate nucleus, PFC, and inferior parietal lobule. Compared with controls and patients who were CP, patients who were CI had increased activations of the SII, cerebellum, and insula. Compared with controls, they also had increased activations of the right precentral gyrus and a reduced recruitment of the left PFC. In patients with PPMS, a decreased composite cognitive score correlated with increased activity of the cerebellum, insula, and SII, as well as decreased PFC activity. T2 LL correlated with decreased PFC recruitment and increased SII recruitment. CONCLUSIONS: In PPMS, an increased recruitment of cognitive-related networks might represent a functional reserve with the potential to limit the severity of cognitive impairment. The accumulation of T2 lesions and the consequent exhaustion of frontal lobe plasticity might contribute to cognitive impairment in PPMS.
TL;DR: The use of functional MRI has disclosed that brain cortical reorganization may play a role in limiting the neuropsychological consequences of structural damage in the different stages of the disease.
Abstract: Magnetic resonance imaging (MRI) techniques have contributed to ameliorate the understanding of the mechanisms responsible for the accumulation of cognitive impairment in patients with multiple sclerosis. Earlier studies demonstrated a relationship of the location of T2-visible lesions in critical brain regions and atrophy of several brain compartments with the severity of cognitive impairment in these patients. More recently, the development of new postprocessing approaches and the application of quantitative MR techniques for the assessment of structural disease-related damage in the brain normal-appearing white matter and gray matter resulted in a better understanding of the factors associated with the onset and development of deficits of several cognitive domains. In addition, the use of functional MRI has disclosed that brain cortical reorganization may play a role in limiting the neuropsychological consequences of structural damage in the different stages of the disease.
TL;DR: MTX should be considered as an effective therapeutic option in RR MS patients with evidence of relevant disease activity, but the potential life-threatening adverse events and the overall benefit—risk ratio must be carefully evaluated at individual patient level.
Abstract: Background: Mitoxantrone (MTX) is an immunosuppressive drug approved for multiple sclerosis (MS) treatment. Objective: The aim of this study is to evaluate and to compare the clinical and neuroradiological responses to MTX in relapsing—remitting (RR) and secondary progressive (SP) MS patients.Methods: We conducted a retrospective, non-randomized, open-label, observational study to evaluate the clinical and neuroradiological response to the drug in 79 patients with RR MS and 210 patients with SP MS.Results: A statistically significant reduction (p < 0.001) in the number of relapses was observed during MTX treatment and in the year after in both RR and SP MS patients. On the contrary, an opposite behavior in terms of disease progression was found in RR compared with SP MS patients, resulting in a statistically significant improvement of the Expanded Disability Status Scale score during the MTX treatment (p < 0.001) and in the year after (p < 0.001) for RR MS patients compared with a continuous, although mil...
TL;DR: A less severe intrinsic lesion damage, a less frequent lesion occurrence in the posterior periventricular WM and the sparing of GM may help to explain the favourable short-/medium-term disease outcome of paediatric multiple sclerosis.
Abstract: Objective To characterise, using conventional and diffusion tensor (DT) MRI, the nature and distribution of lesions and the extent of damage in the brain normal-appearing white matter (NAWM) and grey matter (GM) from a relatively large population of paediatric multiple sclerosis (MS) patients. Methods Brain conventional and DT MRI scans were acquired from 48 patients with paediatric MS (10 clinically isolated syndromes (CIS), 38 relapsing remitting (RR) MS), 30 adult CIS, 27 adult RRMS, 15 paediatric healthy controls (HC) and 18 adult HC. T2-lesion probability maps and DT MRI of lesions, NAWM and GM were compared among controls and MS groups. Results T2-visible lesion volumes did not differ among patient groups, but T2 lesions were more frequently located in the posterior periventricular regions in adult RRMS patients than in adult CIS and paediatric RRMS patients. Adult RRMS patients had a significantly higher lesion average mean diffusivity than paediatric RRMS patients. No DT MRI changes in the NA tissues were found in paediatric and adult CIS patients. DT MRI abnormalities were limited to the NAWM in paediatric RRMS patients, while they involved the NAWM and GM in adult RRMS patients. The extent of NAWM involvement was similar between adult and paediatric RRMS patients and was significantly correlated with T2-visible lesion burden. Conclusions A less severe intrinsic lesion damage, a less frequent lesion occurrence in the posterior periventricular WM and the sparing of GM may help to explain the favourable short-/medium-term disease outcome of paediatric MS.
TL;DR: In LH, the performance of simple motor acts with the dominant lower limb might be achieved through a complex adaptation and interaction between different neuronal pathways and the daily-life environment.
TL;DR: In patients with multiple sclerosis, the term dirty-appeared white matter (DAWM) refers to brain regions of intermediate signal intensity between those of focal lesions and normal-appearing white matter on T2-weighted and proton attenuation–weighted images.
Abstract: In patients with multiple sclerosis (MS), the term dirty-appearing white matter (DAWM) refers to brain regions of intermediate signal intensity between those of focal lesions and normal-appearing white matter (NAWM) on T2-weighted and proton attenuation–weighted images.[1][1][][2][][3]–[4][4]
TL;DR: Novel MR approaches highlighted previously unrecognized or neglected aspects of MS pathophysiology, which are likely to improve the understanding of the heterogeneous clinical manifestations of this condition.
Abstract: Purpose of review This review summarizes novel MRI approaches for the investigation of lesion burden and understanding of the pathophysiology of multiple sclerosis (MS). Recent findings Recent technical advances are improving our ability to detect and define the nature of focal lesions and ‘diffuse’ tissue damage in MS as well as the functional consequences of such structural abnormalities. New contrast agents allow to monitor the pluriformity of MS inflammation. Double inversion recovery sequences enable us to detect and monitor the evolution of MS lesions in the cortex. High and ultra-high field scanners are improving imaging of MS-related abnormalities at an unprecedented resolution. Furthermore, this new generation of scanners has the potential to ameliorate structural and functional MR studies of the disease. All of this has contributed, and is likely to continue to contribute, to the definition of the factors associated with the development of irreversible disability in MS. Finally, new analysis methods have allowed to track regional disease-related changes and are resulting in an increased correlation between MRI and clinical deficits. Summary Novel MR approaches highlighted previously unrecognized or neglected aspects of MS pathophysiology, which are likely to improve our understanding of the heterogeneous clinical manifestations of this condition.
TL;DR: This study confirms the usefulness of multimodal integration of fMRI, EEG and TMS in localizing M1 and the possibility to increase EEG spatial resolution using fMRI information.
TL;DR: The steady correlation observed between conventional and MT MRI measures over time supports the hypothesis of axonal degeneration of fibres passing through focal lesions as one of the factors contributing to the overall MS burden.
Abstract: This study was performed to assess the temporal evolution of damage within lesions and the normal-appearing white matter, measured using frequent magnetization transfer (MT) MRI, in relapsing-remitting multiple sclerosis (RRMS). The relationship of MT ratio (MTR) changes with measures of lesion burden, and the sample sizes needed to demonstrate a treatment effect on MTR metrics in placebo-controlled MS trials were also investigated. Bimonthly brain conventional and MT MRI scans were acquired from 42 patients with RRMS enrolled in the placebo arm of a 14-month, double-blind trial. Longitudinal MRI changes were evaluated using a random effect linear model accounting for repeated measures, and adjusted for centre effects. The Expanded Disability Status Scale (EDSS) score remained stable over the study period. A weak, but not statistically significant, decrease over time was detected for normal-appearing brain tissue (NABT) average MTR (-0.02% per visit; p = 0.14), and MTR peak height (-0.15 per visit; p = 0.17), while average lesion MTR showed a significant decrease over the study period (-0.07% per visit; p = 0.03). At each visit, all MTR variables were significantly correlated with T2 lesion volume (LV) (average coefficients of correlation ranging from -0.54 to -0.28, and p-values from <0.001 to 0.02). At each visit, NABT average MTR was also significantly correlated with T1-hypointense LV (average coefficient of correlation = -0.57, p < 0.001). The estimation of the sample sizes required to demonstrate a reduction of average lesion MTR (the only parameter with a significant decrease over the follow-up) ranged from 101 to 154 patients to detect a treatment effect of 50% in a 1-year trial with a power of 90%. The steady correlation observed between conventional and MT MRI measures over time supports the hypothesis of axonal degeneration of fibres passing through focal lesions as one of the factors contributing to the overall MS burden.
06 Sep 2010