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Biomedical subjects

M Filippi

Publications and source records attributed to M Filippi.

At least 55 records · Page 3Linked to original sources
PubMed2004

A double blind, placebo-controlled, phase II, add-on study of cyclophosphamide (CTX) for 24 months in patients affected by multiple sclerosis on a background therapy with interferon-beta study denomination: CYCLIN.

The authors present and discuss a new protocol for active multiple sclerosis (MS) patients. A double blind randomized controlled multicenter study was planned to study the effects of a combination regimen therapy: cyclophosphamide plus beta interferon versus beta interferon alone on both relapsing-remitting and secondary MS patients with active disease. The primary endpoint of this study is the number of new gadolinium enhancing lesions at MRI evaluation. Secondary endpoints are new T2 lesions, new T1 lesions, T2 lesion load, T1 lesion load, cerebral atrophy, number of patients who were relapse-free, number of patients who improved, yearly relapses, quality of life, disability and cognitive impairment, frequency of neutralizing antibodies, safety of the combination therapy (cyclophosphamide + beta interferon). The study will enroll 225 patients in 25 Italian MS centers. Eligible for the study are patients with either relapsing-remitting or secondary MS according McDonald criteria on 6-24 months beta interferon treatment with active disease (new gadolinium enhancing lesion or who experienced a new relapse on beta interferon treatment). Clinical evaluation will be performed every 4 months, MRI yearly. Vital signs and eventual adverse events will be collected monthly. The study will last 36 months, 12 for the enrollment phase and 24 for the treatment phase. The study will start on April 2004.

Central Nervous System↗
PubMed2004

An MT MRI study of the cervical cord in clinically isolated syndromes suggestive of MS.

Cervical cord magnetization transfer ratio (MTR) histograms were obtained from 45 patients at presentation with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS). The mean values of MTR histogram-derived metrics were not different between CIS patients and healthy control subjects or between patients with and without evidence of disease dissemination in time. Only three patients showed significantly lower cord MTR values than control subjects. These findings suggest the absence of intrinsic structural damage of the cervical cord soon after the onset of CIS suggestive of MS, even in those patients with an early evolution to MS.

Adolescent↗
PubMed2004

Measurement error of two different techniques for brain atrophy assessment in multiple sclerosis.

The measurement errors associated with two techniques for brain atrophy assessment in multiple sclerosis (MS) were estimated. The measurement error of a semiautomated, nonnormalized technique with partial brain coverage was about twofold higher than that of a fully automated, normalized technique with full brain coverage (Structural Image Evaluation of Normalized Atrophy software [SIENA]). As shown by the analysis of data from a clinical trial of glatiramer acetate, the use of SIENA increases the study power to detect a treatment effect on brain volume changes in MS patients.

Atrophy↗
PubMed2004

Magnetization transfer and diffusion tensor MRI show gray matter damage in neuromyelitis optica.

Using magnetization transfer (MT) and diffusion tensor (DT) MRI, the authors assessed the extent of tissue damage of the brain normal-appearing white and gray matter (NAGM) in patients with neuromyelitis optica (NMO). Compared to healthy controls, patients with NMO showed reduced MT ratio and increased mean diffusivity of the NAGM. This challenges the classic notion of a sparing of the brain tissue in the course of NMO.

Adult↗
PubMed2004

Multiparametric MRI in a patient with adult-onset leukoencephalopathy with vanishing white matter.

This is a multiparametric MR study of the first reported patient with adult-onset genetically confirmed vanishing white matter (VWM) disease. It shows that, despite the presence of a severe and diffuse damage of the brain WM, brain gray matter, and cervical cord tissue, the cortical adaptive capacities were relatively preserved. Interpatient variability of brain plasticity may contribute to the known phenotypic variation of patients with VWM disease.

Basal Ganglia↗
PubMed2004

Role of magnetic resonance imaging within diagnostic criteria for multiple sclerosis.

The diagnosis of multiple sclerosis (MS) has been improved in recent decades with the incorporation of paraclinical investigations in diagnostic workup. In the last 15 years, magnetic resonance imaging (MRI) has become an especially valuable tool for supporting MS diagnosis, and specific imaging criteria became fundamental to the guidelines for the diagnosis of MS published in 2001 by an international panel (IP). The new IP criteria include MRI evidence of dissemination in space and time, making it possible to diagnose MS after a single clinical episode. This review considers current evidence concerning the reliability of the new IP criteria for the diagnosis of relapsing-onset MS, discusses strengths and weaknesses of the criteria, and outlines areas which may need modification or should be the focus of future research directed toward improving diagnostic accuracy. It also makes practical recommendations when using MRI and the IP criteria in MS diagnosis, especially in patients with clinically isolated syndromes or atypical presentations. The IP criteria are timely and concrete and introduce an important concept to MS diagnosis. Future modifications, based on emerging evidence, should further facilitate their implementation and improve their accuracy.

Humans↗
PubMed2004

Diffusion tensor and magnetization transfer MR imaging of early-onset multiple sclerosis.

Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS) with the onset of symptoms typically occurring between the age of 20 and 40 years. However, in about 3% to 12% of the cases, the onset of the disease is before 16 years of age. This review summarizes the main results obtained by the application of conventional and non-conventional MRI techniques to the assessment of patients with early-onset MS, which showed that the overall amount of CNS damage in these subjects is mild, compared to that typically detected in the adult-form of the disease. This fits with the notion that an early onset of the disease is associated with a more favourable clinical evolution.

Adult↗
PubMed2004

MR imaging of Devic's neuromyelitis optica.

Devic's neuromyelitis optica (NMO) is a neurological condition characterized by a severe involvement of the optic nerves and spinal cord in a mono- or multi-phasic manner. Recent pathologic, cerebrospinal fluid and conventional magnetic resonance imaging (MRI) studies have shown abnormalities which might help in differentiating patients with NMO from those with multiple sclerosis. This review article summarizes the main results obtained using conventional MRI in NMO, which has contributed to the definition of internationally-accepted diagnostic criteria, and those obtained from the application of modem quantitative MR techniques which are significantly changing our views on NMO pathobiology.

Brain↗
PubMed2004

A functional MRI study of movement-associated cortical changes in patients with Devic's neuromyelitis optica.

Movement-associated cortical changes have been shown in several neurological conditions and were found to be associated to the extent of brain and cord damage. Devic's neuromyelitis optica (DNO) is characterized by a severe involvement of the cord and optic nerve, with sparing of the brain. To assess the actual role of cord pathology on the pattern of movement-associated cortical recruitment, we obtained functional magnetic resonance imaging (fMRI) from patients with DNO and investigated whether the extent of brain activation is correlated with the extent of cervical cord damage. We studied 10 right-handed DNO patients and 15 sex- and age-matched healthy controls. The MRI assessment consisted of the following: (a) fMRI during repetitive flexion extension of the last four fingers of the right and left hand, (b) brain and cervical cord conventional MRI, and (c) cervical cord magnetization transfer (MT) MRI. Compared to controls and for both tasks, DNO patients had an increased recruitment of several regions of the sensorimotor network (primary sensorimotor cortex, postcentral gyrus, middle frontal gyrus, rolandic operculum, secondary sensorimotor cortex, precuneus, and cerebellum) and of several other regions mainly in the temporal and occipital lobes, such as MT/V5, the fusiform gyrus, the cuneus, and the parahippocampal gyrus. For both tasks, strong correlations (r values ranging from -0.76 to -0.85) were found between relative activations of cortical sensorimotor areas and the severity of cervical cord damage. This study shows an abnormal pattern of movement-associated cortical activations in patients with DNO, which extends beyond the 'classical' sensorimotor network and also involves visual areas devoted to motion processing. The correlation found between fMRI changes and the extent of cord damage suggests that such functional cortical changes might have an adaptive role in limiting the clinical outcome of DNO structural pathology.

Adult↗
PubMed2004

T1 relaxation maps allow differentiation between pathologic tissue subsets in relapsing-remitting and secondary progressive multiple sclerosis.

In an attempt to clarify whether T1 relaxation time mapping may assist in characterizing the pathological brain tissue substrate of multiple sclerosis (MS), we compared the T1 relaxation times of lesions, areas of normal-appearing white matter (NAWM) located proximal to lesions, and areas of NAWM located distant from lesions in 12 patients with the relapsing-remitting and 12 with the secondary progressive (SP) subtype of disease. Nine healthy volunteers served as controls. Calculated mean T1 values were averaged across all patients within each clinical group, and comparisons were made by means of the Mann-Whitney U-test. Significant differences were found between all investigated brain regions within each clinical subgroup. Significant differences were also detected for each investigated brain region among clinical subgroups. While T1 values of NAWM were significantly higher in patients with SP disease than in normal white matter (NWM) of controls, no differences were detected when corresponding brain areas of patients with RR MS were compared with NWM of controls. T1 maps identify areas of the brain that are damaged to a different extent in patients with MS, and may be of help in monitoring disease progression.

Adult↗
PubMed2004

Brain tissue loss occurs after suppression of enhancement in patients with multiple sclerosis treated with autologous haematopoietic stem cell transplantation.

To assess whether brain tissue loss occurs after profound and sustained suppression of magnetic resonance imaging (MRI) enhancement, we measured brain volume changes from 10 patients with rapidly evolving secondary progressive multiple sclerosis (MS) treated with autologous haematopoietic stem cell transplantation and followed up for 24 months. An average yearly decrease of brain volume of about 1.9% was observed despite only five enhancing lesions seen on triple dose follow up scans of two patients. This indicates that, in MS, progressive loss of tissue can occur independently of concomitant MRI-visible inflammation.

Artifacts↗
PubMed2003

Whole-brain atrophy in multiple sclerosis measured by two segmentation processes from various MRI sequences.

Recent MRI and pathologic studies have drawn attention to the destructive nature of the multiple sclerosis (MS) disease process, including the early occurrence of axonal and neuronal loss, leading to macroscopic brain and spinal cord atrophy. Measurement of brain atrophy from MRI has emerged as a potential outcome measure and marker of disease severity in MS and neurodegenerative diseases such as Alzheimer's. However, the optimal method for quantifying atrophy has not been established, including the choice of pulse sequence and segmentation algorithm employed. Using two different MRI scanners to ensure generalizability of results, we compared the reproducibility of four pulse sequences and two analysis methods (fully automated [FA] and semi-automated [SA]) when obtaining brain parenchymal fraction (BPF), a normalized measure of whole-brain atrophy, in patients with MS (n=13) and normal controls (n=2). In order to ensure the validity of our fully automated analysis technique, we also used it to evaluate the atrophy rate over nine months in 57 MS patients from the placebo arm of a clinical trial. All pulse sequences were capable of yielding reproducibility of around 1% coefficient of variation (CoV) or better. The best reproducibility was obtained using 2D multi-slice sequences (conventional spin echo [SE] and fluid-attenuated inversion recovery [FLAIR]), with fully automated analysis. Fully automated analysis of the longitudinal data (conventional spin echo) showed an atrophy rate of -0.5% change in BPF per year, in line with previous findings from a similar cohort of patients. In conclusion, BPF measurement is affected by both pulse sequence and segmentation method. Automated measurement has high reproducibility especially when 2D sequences are used. Semi-automated measurement may have increased accuracy, but with a decreased efficiency and reliability.

Adult↗
PubMed2003

Cord damage elicits brain functional reorganization after a single episode of myelitis.

OBJECTIVE: To assess, using fMRI, the brain pattern of movement-associated cortical activations in patients with a previous remitting episode of acute cervical myelitis of possible demyelinating origin and to investigate whether the extent of cortical reorganization is associated with the extent of cervical cord pathology measured using magnetization transfer (MT) MRI. METHODS: From 14 right-handed patients in a chronic and stable phase after an isolated myelitis (male/female = 7/7, mean age = 35.3 years, median disease duration = 21.2 months) involving the cervical cord and 15 sex- and age-matched healthy control subjects, we obtained 1) fMRI during repetitive flexion-extension of the last four fingers of the right hand, 2) brain diffusion tensor MRI, and 3) brain and cervical cord conventional and MT MRI. FMRI data were analyzed using Statistical Parametric Mapping software. Brain mean diffusivity, fractional anisotropy, and MT ratio (MTR) histograms of the normal-appearing white and gray matter and cervical cord MTR histograms were produced. RESULTS: Patients with myelitis had lower average cord MTR (p < 0.0001) and cord MTR histogram peak position (p = 0.002) than control subjects. Compared with healthy volunteers, patients with myelitis showed increased recruitment of the ipsilateral hemisphere in the primary sensorimotor cortex (p < 0.0001), supplementary motor area (p = 0.002), and middle frontal gyrus (MFG) (p < 0.0001). Average cervical cord MTR was inversely correlated with relative activations of the ipsilateral MFG (r = -0.80) and of the ipsilateral postcentral gyrus (r = -0.80). The relative activation of the ipsilateral MFG was also correlated with cervical cord MTR peak position (r = -0.92). CONCLUSIONS: An abnormal pattern of movement-associated cortical activations was found in patients with a previous episode of cervical myelitis. These functional cortical changes might have an adaptive role in limiting the clinical outcome of structural cord damage.

Acute Disease↗
PubMed2003

The utility of MRI in suspected MS [RETIRED]: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

Advancements in imaging technologies and newly evolving treatments offer the promise of more effective management strategies for MS. Until recently, confirmation of the diagnosis of MS has generally required the demonstration of clinical activity that is disseminated in both time and space. Nevertheless, with the advent of MRI techniques, occult disease activity can be demonstrated in 50 to 80% of patients at the time of the first clinical presentation. Prospective studies have shown that the presence of such lesions predicts future conversion to clinically definite (CD) MS. Indeed, in a young to middle-aged adult with a clinically isolated syndrome (CIS), once alternative diagnoses are excluded at baseline, the finding of three or more white matter lesions on a T2-weighted MRI scan (especially if one of these lesions is located in the periventricular region) is a very sensitive predictor (>80%) of the subsequent development of CDMS within the next 7 to 10 years. Moreover, the presence of two or more gadolinium (Gd)-enhancing lesions at baseline and the appearance of either new T2 lesions or new Gd enhancement on follow-up scans are also highly predictive of the subsequent development of CDMS in the near term. By contrast, normal results on MRI at the time of clinical presentation makes the future development of CDMS considerably less likely.

Adult↗