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C Gasperini

Publications and source records attributed to C Gasperini.

At least 55 records · Page 3Linked to original sources
PubMed1998

Correlations between monthly enhanced MRI lesion rate and changes in T2 lesion volume in multiple sclerosis.

Magnetic resonance imaging (MRI) provides a powerful tool for assessing disease activity in multiple sclerosis (MS), and its role as a surrogate marker for monitoring treatment efficacy is now becoming established. The most commonly used MRI parameters in treatment trials are (1) monthly gadolinium-enhanced MRI, with the number of active lesions serving as the outcome measure, and (2) annual lesion load quantification, in which change in MS lesion volume provides the MRI endpoint. We evaluated clinical/MRI correlations and the relationship between these two markers of disease activity in 73 patients with clinically definite MS. Quantification of T2 lesion load was performed at study entry and exit, with a median study duration of 11 months (range, 9 to 14 months). Monthly postgadolinium T1-weighted images were acquired between these time points. Lesion load at study entry was significantly correlated with the baseline Expanded Disability Status Scale (EDSS) score, but no significant longitudinal correlation was demonstrated. The number of enhancing lesions on the entry scan was predictive of subsequent relapse rate over the study duration and also correlated with the subsequent enhancing lesion activity over the study period. A significant correlation was found between change in lesion load and disease activity on the monthly scans. Our results suggest that annual lesion load quantification provides an efficient measure of ongoing disease activity, and this supports its application as a surrogate marker of disease evolution in phase III treatment trials.

Adolescent↗
PubMed1998

Development of neutralizing antibodies in patients with relapsing-remitting multiple sclerosis treated with IFN-beta1a.

Sixty-eight patients with relapsing-remitting multiple sclerosis (RRMS) were treated with 3 million or 9 million i.u. of recombinant interferon-beta1a (recIFN-beta1a) s.c. three times a week for 2 years. Their sera were tested for antibodies neutralizing the IFN (NAb) in a bioassay. Sera with titers > or = 1:20 were considered positive. We detected NAb in 3.2%, 13.8%, and 15.9% of the patients in sera obtained at 3, 6, and 24 months, respectively. The incidence was not related to the IFN dose. Interestingly, during the 6 month baseline period before the start of the study, relapse rates, baseline disability, and the volume of lesions on T2-weighted images were significantly higher in patients who developed NAb during treatment. Because of interpatient variability, no definitive relationship was observed between NAb formation and loss of clinical or magnetic resonance imaging (MRI) response.

Adolescent↗
PubMed1998

A multi-centre longitudinal study comparing the sensitivity of monthly MRI after standard and triple dose gadolinium-DTPA for monitoring disease activity in multiple sclerosis. Implications for phase II clinical trials.

In this study we assessed the safety, efficacy and cost-effectiveness of the use of triple dose gadolinium-DTPA (Gd) in serial monthly brain MRI of patients with multiple sclerosis, such as could be selected for clinical trials. The number of enhancing lesions, the number of new enhancing lesions and the number of active scans were used to evaluate the sensitivity of the contrast-enhanced MRI to disease activity. The dose of Gd, and the effect of introducing a delay between the contrast injection and the scan were both appraised. Every 4 weeks for 3 months, and in two separate sessions, scans were obtained from 40 patients with relapsing-remitting or secondary progressive multiple sclerosis, 5 min (early) and 20 min (delayed) after a standard dose (0.1 mmol/kg) or triple dose (0.3 mmol/kg) Gd injection. There were 435 enhancing lesions (242 of which were new) on the early standard dose scans, 479 (263 new) on the delayed standard dose, 772 (365 new) on the early triple dose and 827 (404 new) on the delayed triple dose. There were 109 scans revealing active disease on the early standard dose scans, 112 on the delayed standard dose, 119 on the early triple dose and 120 on the delayed triple dose. Statistical simulations indicated that the sample sizes needed for both cross-over and parallel-group trials with similar powers are lower if serial monthly triple dose MRI is used. No side-effects were reported and no significant changes in blood test parameters were found throughout the study. This study shows that the serial use of triple dose Gd is safe, and that it increases the sensitivity of serial monthly enhanced MRI in detecting multiple sclerosis activity significantly. Its use should enable preliminary trials of experimental therapies for multiple sclerosis to be conducted in small patient populations, over a short period of time.

Adult↗
PubMed1998

MRI evolution of new MS lesions enhancing after different doses of gadolinium.

OBJECTIVE: To investigate the evolution of multiple sclerosis (MS) lesions enhancing after single dose (SD) or triple dose (TD) of gadolinium-DTPA (Gd). MATERIAL AND METHODS: For 3 months, 30 relapsing-remitting MS patients underwent 2 monthly MRI sessions, consisting of Gd-enhanced T1-weighted scans, after SD (i.e., 0.1 mmol/kg) in one session and TD (i.e., 0.3 mmol/kg) in the other. New enhancing lesions on month 1 and month 2 follow-up scans were studied and for them any persistence of enhancement was evaluated on the scans obtained the next month. RESULTS: In all, 151 lesions enhancing after both SD and TD and 91 lesions enhancing only after TD entered the analysis. After 1 month, for the 151 lesions enhancing after both SD and TD, 73 (48%) were not enhancing, 50 (33%) were still enhancing after both SD and TD and 28 (19%) were enhancing only after TD. For the 91 lesions enhancing only after TD, 61 (67%; P<0.005) were not enhancing, 16 (18%; P<0.01) were still enhancing only after TD and 14 (15%; P=NS) showed enhancement after both SD and TD. CONCLUSION: Enhancing lesions in patients with MS are heterogeneous. Those enhancing only after TD of Gd are characterized by a milder and shorter opening of the blood-brain barrier.

Blood-Brain Barrier↗
PubMed1998

A preliminary study comparing the sensitivity of serial monthly enhanced MRI after standard and triple dose gadolinium-DTPA for monitoring disease activity in primary progressive multiple sclerosis.

We performed this study to evaluate and compare the numbers of total and new enhancing lesions detected on serial monthly brain magnetic resonance imaging (MRI) after the injection of a standard dose (SD) and a triple dose (TD) of gadolinium-DTPA (Gd) in patients with primary progressive multiple sclerosis (PPMS). Every 4 weeks for 3 months and in two separate sessions, MRI scans were obtained from 5 patients with PPMS, 5 (early) and 20 minutes (delayed) after SD (0.1 mmol/kg) or TD (0.3 mmol/kg) Gd injection. In 2 patients, T1-weighted scans with a magnetization transfer pulse (MT) after SD and TD injection were also obtained. There were 13 enhancing lesions (5 of which were new) on the early SD scans, 15 (5 new) on the delayed SD scans, 17 (6 new) on the early TD scans and 18 (7 new) on the delayed TD scans. TD MRI scans detected more enhancing lesions than SD scans in 3 patients (two of them were those with the lowest disability). The application of the MT pulse did not change the numbers of enhancing lesions seen after the injection of SD and TD of Gd in the remaining two patients. No side effects were reported and no significant changes in blood test parameters were found throughout the study. Our results suggest that serial monthly TD MRI, delayed scanning, MT T1-weighted scans or their combination, although safe, have a limited role for monitoring disease evolution in patients with PPMS.

Adult↗
PubMed1998

Detecting new lesion formation in multiple sclerosis: the relative contributions of monthly dual-echo and T1-weighted scans after triple-dose gadolinium.

In this study, we evaluated the frequency of formation of new lesions on brain magnetic resonance imaging (MRI) from patients with relapsing-remitting multiple sclerosis (MS) and defined the relative contributions of unenhanced and enhanced MRI. Every 4 weeks for 3 months, dual-echo and postcontrast T1-weighted (5 min after the injection of 0.3 mmol/kg gadolinium-DTPA) scans were obtained from 28 patients with relapsing-remitting MS. New lesions were defined as those present on dual-echo and/or postcontrast T1-weighted scans but with no corresponding MRI abnormalities on any of the preceding scans. A total of 111 newly formed lesions were detected during the follow-up on dual-echo and postcontrast T1-weighted scans (i.e., an average of 1.3 lesions per patient per month). Ninety-eight (88%) of such lesions were seen on both dual-echo and postcontrast T1-weighted scans, whilst 13 (12%) were seen only with one of the two techniques: 9 only on dual-echo and 4 only on postcontrast scans. Five of the 98 new lesions seen by both techniques were seen by postcontrast scans 1 month before their appearance on dual-echo scans. Our study suggests that both dual-echo and postcontrast T1-weighted scans are useful to detect newly formed lesions in patients with MS. This is of importance when using MRI to monitor the efficacy of treatments which may halt MS lesion formation.

Adult↗
PubMed1998

Determinants of Gd-enhanced MRI response to IFN-beta-1a treatment in relapsing-remitting multiple sclerosis.

The decision to use interferon beta (IFN-beta) as a treatment for relapsing-remitting multiple sclerosis (RRMS) is based on both clinical characteristics and course of the disease. To better identify the profile of responders, the relationships between baseline clinical/MRI characteristics and therapeutical response was analyzed in 49 patients with RRMS randomly assigned to receive subcutaneously 3 or 9 MIU of IFN-beta-1a. The therapeutical response was evaluated as a per cent change in the mean number and volume of monthly Gd-enhancing lesions in both first (early response) and second (late response) 6-month period of treatment, compared to the 6-month pre-treatment period. A better early response was seen in patients with a lower number of relapses during the pre-treatment period, while the late response was favourably influenced by a lower baseline EDSS and the high dose. Our findings suggest that the effect of IFN-beta-1 a on disease MRI activity is dose-related and dependent on the relapse rate and the level of disability before treatment.

Adjuvants, Immunologic↗
PubMed1998

Effect of training and different measurement strategies on the reproducibility of brain MRI lesion load measurements in multiple sclerosis.

In this study, we evaluated the intra- and interobserver variabilities in measuring lesion load of brain MRI abnormalities present on proton-density scans from patients with MS, using using both manual outlining or a semiautomated local thresholding technique (LTT). We also evaluated how these variabilities were affected by the use of standard rules for lesion load measurements, training, and different measurement strategies. The intraobserver variabilities obtained after establishing rules for lesion load measurements and training were not significantly different from those obtained before any consensus among the observers, both for manual outlining and for the LTT. On the contrary, the interobserver variabilities obtained with manual outlining or the LTT were significantly reduced when rules for lesion load measurements were used. For manual outlining, the intraobserver variability did not significantly change when the measurements were performed after an experienced radiologist identified lesions or when using adjacent slices and the corresponding T2-weighted images as reference for lesion identification. On the contrary, for the LTT, the intraobserver variability was significantly reduced by the use of the radiologic marking. The interobserver variabilities for both manual outlining and the LTT were reduced compared with the free condition when these measurement strategies were used. Our findings demonstrate that both lesion identification and outlining are important sources of variation for MRI lesion load measurements in MS and that there are simple strategies to reduce such variation that might be useful when planning clinical trials.

Brain↗
PubMed1998

Effect of steroids on Gd-enhancing lesions before and during recombinant beta interferon 1a treatment in relapsing remitting multiple sclerosis.

The aim of this study was to investigate whether a concomitant treatment with recombinant interferon beta 1a (rIFN beta-1a) modifies the effect of steroids on the blood-brain barrier (BBB) in relapsing remitting MS patients, as evaluated by enhanced MRI of the brain. We evaluated 19 patients with a clinical relapse treated only with intravenous methylprednisolone (IVMP; 1 g daily for 6 days), and 10 patients who experienced a clinical relapse and were treated with IVMP (1 g daily for 6 days) during an rIFN beta-1a treatment period. The number and volume of enhancing lesions were analyzed on four serial MR images obtained at monthly intervals (one scan before and three scans after IVMP treatment). A significant reduction in the mean number and volume of enhancing lesions was seen in the first scan after IVMP treatment in all patients. However, while persistently low enhancement was seen in the follow-up scans of patients treated with rIFN beta-1a, a rebound effect (i.e., increase in the number and volume of gadolinium-enhancing lesions) was observed in the other patients during the follow-up. These data suggest that rIFN beta-1a prolongs the beneficial effect of steroids on the BBB.

Adult↗
PubMed1997

Four-year follow-up of a case of acute multiple sclerosis of the Marburg type.

We describe the clinical course, treatment and magnetic resonance findings during a four-year follow-up of a patient with acute multiple sclerosis of the Marburg type, treated with steroid and mannitol therapy, who survived the first bout. Although the course of the disease was clinically indistinguishable from relapsing-remitting multiple sclerosis, our case was characterized by peculiar features. These included the need for protracted steroid therapy and the remarkable tendency of MRI lesions to resolve completely.

Adult↗
PubMed1997

Randomized placebo-controlled trial of mitoxantrone in relapsing-remitting multiple sclerosis: 24-month clinical and MRI outcome.

We designed a randomized, placebo-controlled, multicentre trial involving 51 relapsing-remitting multiple sclerosis patients to determine the clinical efficacy of mitoxantrone treatment over 2 years. Patients were allocated either to the mitoxantrone group (27 patients receiving I.V. infusion of mitoxantrone every month for 1 year at the dosage of 8 mg/m2) or to the placebo group (24 patients, receiving I.V. infusion of saline every month for 1 year) using a centralized randomization system. Disability at entry and at 12-24 months was evaluated by four blinded neurologists trained in the application of the Kurtzke Expanded Disability Scale (EDSS). In addition, the number and clinical characteristics of the exacerbations over the 24 months were recorded by the local investigators. MRI, at 0, 12 and 24 months, was performed with a 0.2 T permanent unit. MRI data were analysed by two blinded neuroradiologists. All patients underwent a clinical evaluation. A statistically significant difference in the mean number of exacerbations was observed between the mitoxantrone group and placebo group both during the 1st and the 2nd year. Although there was no statistically significant benefit in terms of mean EDSS progression over 2 years, the proportion of patients with confirmed progression of the disease, as measured by a one point increase on the EDSS scale, was significantly reduced at the 2nd year evaluation in the mitoxantrone group. Forty-two (23 mitoxantrone, 19 placebo) patients underwent all MRI examinations during the 24-month period. We observed a trend towards a reduction in the number of new lesions on T2-weighted images in the mitoxantrone group. Our study suggests that mitoxantrone might be effective in reducing disease activity, both by decreasing the mean number of exacerbations and by slowing the clinical progression sustained by most patients after 1 year from the end of treatment.

Adjuvants, Immunologic↗
PubMed1997

Quantitative magnetic resonance analysis in vascular dementia.

The potential role of magnetic resonance imaging (MRI) in differentiating between specific causes of cognitive decline in patients with vascular dementia (VD) has not yet been fully established. We therefore decided to assess the supratentorial cerebral contents in 24 patients with a diagnosis of probable VD and in 24 normal subjects, matched for age and education level, using MRI volumetric parameters obtained by means of a quantitative method. The volumes of subarachnoid and ventricular spaces, cerebral tissue, and hyperintense areas on T2-weighted images were calculated. In order to reduce interindividual variability caused by differences in intracranial size, each absolute measurement was normalized to the relative size of the intracranial volume. In addition, we calculated the ratio between the areas of the corpus callosum (CC) and supratentorial brain at the same level on the T1-weighted image midsagittal plane. The MRI data were correlated with the deterioration of cognitive functions. Patients with VD showed significantly lower cerebral tissue volume and CC area, and higher ventricular space volume than normal subjects. Furthermore, the total volume of the T2 signal alterations was higher in VD patients than in normal subjects. In VD patients, this volume was found to be proportional to the increase in the volume of the ventricular space. On the other hand, no correlation was found between the volume of the T2 signal alterations and the area of the CC. The degree of global cognitive dysfunction and the score of each neuropsychological test did not show any correlation with the MRI data. Our results suggest that ventricular enlargement in VD patients is correlated with the increase in volume of the T2 signal abnormalities, but that the degree of global cognitive dysfunction is not influenced by the volume of these T2 signal abnormalities. Furthermore, the CC atrophy does not influence the score of any neuropsychological test or the degree of global cognitive dysfunction.

Age Distribution↗
PubMed1997

The influence of clinical relapses and steroid therapy on the development of Gd-enhancing lesions: a longitudinal MRI study in relapsing-remitting multiple sclerosis patients.

Fifty-three patients with relapsing-remitting multiple sclerosis who had monthly Gd (gadolinium) enhanced MRI (Magnetic Resonance Imaging) and clinical evaluation, were divided into two subgroups: 1) patients with a clinical relapse, treated with IVMP (intravenous methylprednisolone) and at least one enhancing lesion on MRI. 2) patients who did not have a clinical relapse but with at least one enhancing lesion on MRI. In group 1, we evaluated the number and volume of enhancing lesions on the scan before and three scans after IVMP therapy; in group 2, we considered the first scan with enhancing lesions and the subsequent three scans. The mean number and volume of enhancing lesions on the first scan was significantly higher in patients with clinical relapse compared to patients without clinical relapse. In group 1, we found a consistent reduction in the first scan following steroid treatment which returned to initial levels at the following scan. Both volumetric and numerical evaluation are appropriate MRI outcome measures in monitoring therapeutic trials.

Adult↗
PubMed1997

No increase of serum autoantibodies during therapy with recombinant human interferon-beta1a in relapsing-remitting multiple sclerosis.

OBJECTIVES: The present investigation was aimed at establishing whether interferon (IFN)-beta would induce the synthesis of autoantibodies in patients affected by multiple sclerosis (MS). MATERIALS AND METHODS: The titres of different autoantibodies were measured in a group of 68 relapsing-remitting MS patients before and during treatment with human recombinant IFN-beta1a (3 MIU or 9 MIU subcutaneously 3x a week). ANA, anti-thyroid, anticardiolipin serum autoantibodies were assayed in all cases: when patients were found positive to ANA > 1 : 40, they were also tested for anti-DNA and anti-ENA antibodies. RESULTS: No increase was found in autoantibodies synthesis during 6 months of r-hIFNbeta1a therapy, either at low or high dosages. The percentage of patients positive to different types of autoantibodies varied between 0 and 29%, which are values similar to those already reported in untreated MS patients. CONCLUSION: Our data indicate that the short-term use of IFN-beta1a in MS is safe in terms of the induction of humoral autoimmune responses: however, further follow-up is needed to confirm these findings during long-term treatments.

Adjuvants, Immunologic↗
PubMed1997

Gadolinium enhanced MRI predicts clinical and MRI disease activity in relapsing-remitting multiple sclerosis.

The aim of the study was to evaluate the predictive power of baseline gadolinium (Gd) enhanced MRI in relation to subsequent clinical and MRI activity. Sixty eight patients with clinically definite relapsing-remitting multiple sclerosis had a baseline Gd enhanced MRI and were followed up clinically and by monthly Gd enhanced MRI for six months. The occurrence of relapses during the follow up period was predicted by the presence of at least one enhancing lesion on the baseline MRI (P < 0.05). The number and volume of enhancing lesions at baseline were significantly associated with both enhancing lesions observed during the follow up period (P < 0.0001) and the accumulation of abnormality on T2 weighted images (P < 0.0001). Moreover, the presence of three or more enhancing lesions at baseline scan was consistently associated with the development of permanent abnormalities on T2 weighted images six months later. The study suggests that the number and volume of Gd enhancing lesions at a single examination are strong short term predictors of subsequent clinical and MRI activity.

Adult↗
PubMed1997

MRI measures and their relations with clinical disability in relapsing-remitting and secondary progressive multiple sclerosis.

To further evaluate the relationship between clinical disability and Magnetic Resonance Imaging (MRI) lesion burden, we examined 85 patients with clinically definite multiple sclerosis (54 relapsing-remitting and 31 secondary progressive). This cross-sectional study reports on the correlations between total and infratentorial lesion volume on both T1 and T2 weighted images, and overall physical disability measured by Expanded Disability Status Scale, ambulation index and individual functional systems. Assessment of the hypointense lesion load on T1 weighted images rather than the hyperintense lesion load on T2 weighted images at brain MRI was shown to be useful for differentiating relapsing-remitting from secondary progressive Multiple Sclerosis. A weak relationship between disability and total lesion volume on both T1 and T2 weighted images was found in relapsing-remitting Multiple Sclerosis. In secondary progressive Multiple Sclerosis, infratentorial lesion volume on T2 weighted images represents the only marker of disability. Finally, the presence of cerebellar, brainstem and mental impairment was significantly associated to a greater total lesion volume on MRI, while no relationship was found with other functional systems.

Adolescent↗
PubMed1997

Interscanner variation in brain MRI lesion load measurements in MS: implications for clinical trials.

We evaluated the effect of interscanner variation on brain MRI-measured lesion volumes and measurement reproducibility in MS. Twenty clinically definite MS patients were each scanned on two or three scanners (a total of 14 scanners were used). In addition, a formalin-fixed MS brain was studied on eight scanners from different manufacturers and with different field strengths. For the formalin-fixed MS brain, on each machine we obtained two scans with slice thicknesses of 5 and 3 mm. Only 5-mm-thick slices were obtained from patients. The lesion volume present on each scan was evaluated three times by a single observer in random order, using a local thresholding technique. In two groups of eight patients scanned on machines with different field strengths, the mean lesion volumes present on scans obtained at 1.5 T were significantly higher than those measured on scans obtained with machines operating at 0.5 and 1.0 T (p < 0.01). When a single observer repeatedly evaluated the same scan, a median introbserver agreement of 98.7% (95% CI, 97.9 to 99.1) was achieved. However, when the observer evaluated the scans from different MRI scanners, the agreement (an interscanner agreement) fell to 91.1% (CI, 90.2 to 94.1). When only scanners operating at 1.5 T were considered, the median interscanner agreement was 96.7% (CI, 95 to 97.5). Also, for the formalin-fixed MS brain, the intraobserver agreements obtained with both slice thicknesses were significantly higher than the corresponding interscanner agreements. The interscanner agreement, but not the intraobserver agreement, obtained with a slice thickness of 3 mm was higher than that obtained with a slice thickness of 5 mm. Our results indicate that lesion volume measurements in MS are influenced significantly by the use of different MR scanners and that a patient included in a serial study should be always scanned with the same MR machine using 3-mm thick slices.

Adult↗