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C Pozzilli

Publications and source records attributed to C Pozzilli.

At least 55 records · Page 3Linked to original sources
PubMed2000

Global immune disregulation in multiple sclerosis: from the adaptive response to the innate immunity.

Increasing evidences show a global immune disregulation in multiple sclerosis (MS). The possible involvement of myelin and non-myelin (auto-)antigens in the autoaggressive process as well as the disregulation of both adaptive and innate immunity challenge the concept of specific immunotherapy. T cells at the boundary between innate and adaptive immunity, whose immunoregulatory role is becoming increasingly clear, have recently been shown to bear relevance for MS pathogenesis. Global immune interventions (and type I interferons may be considered as such) aimed at interfering with both innate and acquired immune responses seem to be a most promising therapeutic option in MS.

Humans↗
PubMed2000

Brain atrophy in relapsing-remitting multiple sclerosis: relationship with 'black holes', disease duration and clinical disability.

Recent MRI studies in multiple sclerosis have highlighted the potential role of brain atrophy evaluation as a putative marker of disease progression. In the present study, we evaluated the supratentorial and infratentorial brain volume in patients with relapsing remitting multiple sclerosis (RR MS) and in healthy subjects. Moreover, we determined whether brain volumes of MS patients are associated with different aspects of brain MRI abnormalities and clinical findings. Two-dimensional acquired MRI was performed on 52 relapsing-remitting multiple sclerosis and 30 healthy subjects. The volume of supratentorial and infratentorial structures was measured in selected representative slices. Gd-enhancement, T2 hyperintense, T1 hypointense (i.e. 'black holes') total lesion load, as well as the area of corpus callosum was calculated in the MS group and related to brain volume measures. Correlations between MRI parameters and clinical features were also considered. MS patients had significantly lower supratentorial, infratentorial brain volume and corpus callosum area than healthy subjects (P<0.01). Supratentorial brain volume was significantly related to corpus callosum area (r=0.58; P<0.01) and T1 hypointense lesion load (r=0.48; P<0.01), but not with T2 hyperintense lesion load. Infratentorial/supratentorial ratio was significantly associated with disease duration and EDSS score (r=-0.34; P=0.02 and r=-0.49; P<0.01, respectively). This study documents that brain atrophy is an early MRI finding in RR MS and it is closely related to 'black holes' burden. The use of relative values (infratentorial/supratentorial ratio) may increase the conspicuity of correlation between clinical and MRI findings.

Adolescent↗
PubMed2000

The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis. European Study Group on Interferon beta-1b in secondary progressive multiple sclerosis.

The recently completed European trial of interferon beta-1b (IFNbeta-1b) in patients with secondary progressive multiple sclerosis (SP multiple sclerosis) has given an opportunity to assess the impact of treatment on cerebral atrophy using serial MRI. Unenhanced T(1)-weighted brain imaging was acquired in a subgroup of 95 patients from five of the European centres; imaging was performed at 6-month intervals from month 0 to month 36. A blinded observer measured cerebral volume on four contiguous 5 mm cerebral hemisphere slices at each time point, using an algorithm with a high level of reproducibility and automation. There was a significant and progressive reduction in cerebral volume in both placebo and treated groups, with a mean reduction of 3.9 and 2.9%, respectively, by month 36 (P = 0.34 between groups). Exploratory subgroup analyses indicated that patients without gadolinium (Gd) enhancement at the baseline had a greater reduction of cerebral volume in the placebo group (mean reduction at month 36: placebo 5.1%, IFNbeta-1b 1.8%, P < 0.05) whereas those with Gd-enhancing lesions showed a trend to greater reduction of cerebral volume if the patient was on IFNbeta-1b (placebo 2.6%, IFNbeta-1b 3.7%; P > 0.05). These results are consistent with ongoing tissue loss in both arms of this study of secondary progressive multiple sclerosis. This finding is concordant with previous observations that disease progression, although delayed, is not halted by IFNbeta. The different pattern seen in patients with and without baseline gadolinium enhancement suggests that part of the cerebral volume reduction observed in IFNbeta-treated patients may be due to the anti-inflammatory/antioedematous effect of the drug. Longer periods of observation and larger groups of patients may be needed to detect the effects of treatment on cerebral atrophy in this population of patients with advanced disease.

Adult↗
PubMed2000

Contrast-enhanced magnetic resonance activity in relapsing remitting multiple sclerosis patients: a short term natural history study.

Magnetic resonance imaging (MRI) has been used to study the history of multiple sclerosis (MS). We analyze the relationship between MRI activity in the first scan compared to the subsequent five scans, and we evaluate whether a shorter observation period of 3 months may predict the subsequent 3 months. Monthly enhanced MRI was performed in 103 relapsing remitting (RR) MS patients for 6 months. Thirty-five per cent of patients had an inactive scan on the initial examination. More than 80% of them developed MRI activity during the following 5 months. Eighteen per cent of patients had three consecutive inactive scans; 65% of them had at least one active scan on the subsequent 3 monthly MRI's. The relationship between the first scan and all subsequent scans demonstrates a clear weakening over time. Eighty-two per cent of patients had at least one active scan during the initial 3 consecutive months, the chance of becoming inactive decreased from 23% to 0% over the subsequent 3 months, according with the mean number of enhancing lesions during the first 3 months. These results suggest that neither a single scan nor a short baseline of 3 months may adequately describe the natural history of disease in an individual RRMS patient.

Adult↗
PubMed2000

Antinuclear antibodies and response to IFNbeta-1a therapy in relapsing-remitting multiple sclerosis.

We determined whether positive ANA was related to response to rIFNss-1a in 62 relapsing-remitting MS patients. According to the presence of antinuclear antibodies (ANA) at baseline and during the first 6 months of treatment, patients were sorted in different groups. The clinical and MRI outcome during short-term (6 months) and long-term (24 months) treatment period was not statistically different between the groups. Therefore, the response to IFNbeta-1a seems not to be influenced by ANA occurrence either before or during treatment. When the analysis was extended to other autoantibodies (i. e. antithyroid, anticardiolipin) similar results were obtained.

Adjuvants, Immunologic↗
PubMed2000

MRI of spinal cord in MS.

Over the last 10 - 15 years, magnetic resonance imaging techniques have had a major impact in understanding and managing multiple sclerosis. The present review briefly summarises the current usefulness of spinal cord MRI in MS disease, examining the frequency, distribution and main characteristics of spine MS plaques; the differential diagnosis with other spinal cord disease was also described. Finally we considered how newer imaging sequences when added to semi-automated quantitative methods, may give us a putative tool to reliably quantify subtle changes which develop on the spinal cord of MS patients over time.

Diagnosis, Differential↗
PubMed1999

Cumulative effect of a weekly low dose of interferon beta 1a on standard and triple dose contrast-enhanced MRI from multiple sclerosis patients.

In patients with multiple sclerosis (MS), we assessed the short- and long-term effects of a weekly low dose of recombinant human interferon beta 1a (rh-IFN beta 1a) on the development of new magnetic resonance imaging (MRI) lesions enhancing at different gadolinium-DTPA (Gd) doses. Every 4 weeks, standard dose (SD) (0.1 mmol/kg of Gd) and triple dose (TD) (0.3 mmol/kg of Gd) Gd-enhanced brain MRI scans were obtained from 18 patients with relapsing-remitting MS for 3 months before treatment, 4 months after treatment initiation (treatment period [TP] I) and 4 months after 1 year of treatment (TP II) with 44 microg of rh-IFN beta 1a subcutaneously, once a week. The mean numbers of new enhancing lesions/patient/month were 1.4 (baseline), 1.1 (TP I) and 0.7 (TP II) on SD scans and 2.4 (baseline), 1.3 (TP I) and 0.8 (TP II) on TD scans. On average, treatment decreased the rate of new enhancing lesion appearance by 24% (SD scans) and 45% (TD scans) during TP I and by 52% (SD scans) and 66% (TD scans) during TP II. This study indicates that the effect of 44 microg of rh-IFN beta 1a given once a week on MRI-monitored MS activity increases over time. It also suggests that TD MRI is useful in detecting early treatment effect, that would otherwise be missed.

Adjuvants, Immunologic↗
PubMed1999

Use of Bacille Calmette-Guèrin (BCG) in multiple sclerosis.

We studied the effect of Bacille Calmette-Guerin (BCG) vaccine as an immunomodulator in MS. According to the guidelines for clinical trials in MS, a single crossover, MRI-monitored trial was performed in 14 patients with relapsing-remitting MS. After treatment, MRI activity was significantly reduced. No major adverse effects were reported. Adjuvant therapy with BCG vaccine was safe and merits study in MS.

Adjuvants, Immunologic↗
PubMed1999

Further study on the specificity and incidence of neutralizing antibodies to interferon (IFN) in relapsing remitting multiple sclerosis patients treated with IFN beta-1a or IFN beta-1b.

The development of neutralizing antibodies (NAbs) to interferon (IFN) is a common phenomenon of IFN beta therapy for relapsing-remitting multiple sclerosis (RRMS) patients. Here we examine the specificity of NAbs developed during therapy for RRMS with recombinant interferon (rIFN) beta-1a or rIFN beta-1b, and study the effect of switching from rIFN beta-1a to rIFN beta-1b on the incidence and specificity of NAbs. The relative ability to neutralize rIFN beta-1a and beta-1b was assayed in sera positive for NAbs derived from RRMS patients treated with either rIFN beta-1a (N=9) or rIFN beta-1b (N=16), while the incidence and specificity of NAbs to IFN beta developed during therapy were studied in 50 RRMS patients who were treated for two years with rIFN beta-1a followed by a further year either switching to rIFN beta-1b (N=34) or continuing treatment with rIFN beta-1a (N=16). The results show that all positive sera, independent of the source, may recognize both forms of rIFN beta and that a further year of treatment does not significantly affect the incidence and specificity of the NAbs developed during the first two years of treatment even if treatment is switched to a different type of IFN beta. The data then suggests that it is unlikely that the administration of rIFN beta-1b to anti-rIFN beta-1a NAbs-positive patients can overcome the inhibitory effect exerted by the serum antibodies (and vice versa), and that a further period of treatment with IFN beta-1b in patients previously treated with rIFN beta-1a does not significantly change the pattern of antibody response to IFN beta.

Adjuvants, Immunologic↗
PubMed1999

T cell response to myelin basic protein before and after treatment with interferon beta in multiple sclerosis.

Studies on the in vivo effects of interferon-beta (IFNbeta) therapy on autoreactive T cells have never been carried out in multiple sclerosis (MS). We investigated the T cell response to myelin basic protein (MBP), before and after IFN-beta therapy, raising MBP-specific T cell lines (TCL) from the peripheral blood of six MS patients with a satisfactory response to the treatment. IFNbeta did not affect the relative frequency and epitope specificity of the TCL. After IFNbeta therapy, the production of interleukin-4 was decreased in MBP-stimulated TCL while the secretion of interferon-gamma was increased in unstimulated TCL. Interleukin-10 and tumor necrosis factor-alpha did not show significant variations. This finding supports recent suggestions about the complexity of the T helper 1/T helper 2 paradigm in MS and other organ-specific autoimmune diseases. In fact, the beneficial effects of IFNbeta do not exclude an immunostimulatory action that may involve potentially autoreactive T cells. This has implications for future treatment options, including combination therapies.

Adult↗
PubMed1999

MRI in multiple sclerosis during the menstrual cycle: relationship with sex hormone patterns.

We investigated MRI activity in MS during the menstrual cycle in relation to physiologic sex hormone fluctuations. Eight women with relapsing-remitting MS were submitted to serial brain gadolinium-enhanced MRI examinations over a 3-month period in two alternate follicular and luteal phases of the menstrual cycle. The ratio of progesterone/17-beta-estradiol during the luteal phase was significantly associated with both number (r = 0.6, p = 0.03) and volume (r = 0.7, p = 0.009) of enhancing lesions, providing support for a role of these hormones as immunomodulatory factors in MS.

Adult↗
PubMed1999

A comparison of the sensitivity of monthly unenhanced and enhanced MRI techniques in detecting new multiple sclerosis lesions.

In this longitudinal study, the sensitivities of three magnetic resonance imaging techniques for detecting the appearance of new lesions in multiple sclerosis (MS) were evaluated and compared. Dual-echo conventional spin-echo (CSE), fast fluid-attenuated inversion recovery (fast-FLAIR) and post-contrast T1-weighted scans were obtained on four occasions, each separated by 28 days, from 18 patients with relapsing-remitting MS using a 1.5-T machine. New lesions seen using each sequence during the follow-up were counted by agreement by four observers in two stages (stage 1: random review of complete sets of scans from each technique; stage 2: side-by-side review with a 'retrospective' count of new lesions). At stage 1, 1.44 new lesions per patient per month were detected on CSE scans, 1.88 on fast-FLAIR (31% more than CSE) and 2.07 on post-contrast T1-weighted scans (44% more than CSE) (P = 0.03). Differences were, however, reduced after stage 2: fast-FLAIR detected 29% and post-contrast T1-weighted scans detected 31% more new lesions than CSE(P = 0.08). The combination of fast-FLAIR and post-contrast scans detected 144 new lesions, whilst the usual combination of CSE and post-contrast scans detected 133 new lesions. This study indicates that enhanced MRI remains the most sensitive method for detecting 'active' lesions in MS and that fast-FLAIR may be used when monitoring short-term disease activity in MS, either natural or modified by treatment.

Adult↗
PubMed1999

Magnetic resonance imaging outcome of new enhancing lesions in relapsing-remitting multiple sclerosis patients treated with interferon beta1a.

We investigated whether interferon-beta1a modifies the course of new enhancing lesions in relapsing-remitting multiple sclerosis. Sixty-eight patients were studied by monthly magnetic resonance imaging (MRI) in a pretest-posttest design including 6 months of observation and 6 months of treatment. We examined the course of new Gd-enhancing lesions on two consecutive scans during observation and during treatment. Lesions detected during treatment were also analyzed by MRI 1 year later for persistence of enhancement, persistence of T2 hyperintensity, development of T1 hypointensity, or disappearance. Among the enhancing lesions detected by observation and treatment MRI, respectively, Gd-enhancement persisted at 2 months in 20% and 3% (P < 0.001), T2 hyperintensity persisted in 86% and 63% (P < 0.03), and T1 hypointensity developed in 49% and 15% (P < 0.01). Progression to T1 hypointensity was significantly more frequent in larger lesions during both the observation and treatment periods (P < 0.01). No reenhancement of plaques was present at 1-year follow-up; a further reduction in T2 hyperintensity (63% vs. 39%) was observed while T1 hypointensity remained unchanged. Both the duration of Gd enhancement and the short-term MRI course of new enhancing lesions benefited by treatment with recombinant interferon-beta1a treatment.

Adjuvants, Immunologic↗
PubMed1999

Fatigue and magnetic resonance imaging activity in multiple sclerosis.

Fatigue is a frequent and often severe symptom in multiple sclerosis. Pathogenic mechanisms proposed for fatigue include the release of proinflammatory cytokines, which is thought to have an important effect on changes in the blood-brain barrier (BBB). To investigate whether fatigue is related to BBB disruption we studied 11 relapsing-remitting MS patients participating in a multicenter longitudinal study comparing the sensitivity of monthly enhanced magnetic resonance imaging (MRI) after standard-dose and triple-dose injection of gadolinium-diethylene triaminopentoacetic acid (Gd-DTPA). Serial Gd-enhanced MRI studies were performed in two separate sessions every 4 weeks for 3 months. An expanded version of the Fatigue Severity Scale, including 29 items, was administered 24 h before each MRI examination. No relationship was found between the number and volume of Gd-enhancing lesions and fatigue scores at any monthly examination over the study period. Furthermore changes in MRI activity were not significantly related to changes in fatigue scores. These results were obtained on triple-dose delayed scanning, which is more sensitive than standard-dose scanning in detecting areas of BBB disruption. Our preliminary results thus do not support the hypothesis of a relationship between BBB alterations and fatigue severity in multiple sclerosis.

Adult↗
PubMed1999

Magnetic resonance outcome of new enhancing lesions in patients with relapsing-remitting multiple sclerosis.

The aim of the study was to monitor the natural history of new enhancing lesions in multiple sclerosis (MS) by means of serial gadolinium-enhanced magnetic resonance imaging (MRI). Out of the 63 new enhancing lesions seen on the baseline scan, belonging to 26 relapsing-remitting MS patients, 26 (40%), nine (14%) and four (6%) lesions showed persisting enhancement at first, second and third follow-up scan, respectively. At the end of 5 months of follow-up, 58 (92%) of the new enhancing lesions were detected as T2 hyperintensities, 24 (38%) as T1 hypointensities ('black holes'), and five lesions (8%) disappeared in both T2 and T1 weighted images. Duration of gadolinium enhancement of at least two consecutive scans significantly influenced the development of 'black holes'. No significant correlation was observed between volume, location, configuration of enhancement at baseline and final outcome of the lesion. In individual cases, different evolution of new enhancing lesions was observed at the same time. In conclusion, this study documented that different outcomes of new lesions are unrelated either to the individual patient or to the baseline MRI characteristics. However, prolonged blood-brain-barrier disruption as shown by persisting enhancement significantly influences the lesion outcome.

Adolescent↗
PubMed1999

Interferon beta treatment for multiple sclerosis has a graduated effect on MRI enhancing lesions according to their size and pathology.

OBJECTIVE: The ability of recombinant human interferon beta-1a (rh-IFN beta-1a) to suppress multiple sclerosis activity, evaluated from MRI, was assessed across a range of lesions enhancing at different gadolinium-DTPA (Gd) doses and with different sizes. METHODS: Every 4 weeks, standard dose (Sd; 0.1 mmol/kg Gd) and triple dose (Td; 0.3 mmol/kgGd) MRI were obtained from 18 patients with relapsing-remitting multiple sclerosis for 3 months before and 4 months after starting treatment with 44 microgram rh-IFN beta-1a subcutaneously, once a week. RESULTS: The total numbers of enhancing lesions were 145 and 126 on Sd scans and 278 and 192 on the Td scans obtained before and after treatment. The introduction of treatment decreased, on average, the rate of appearance of new enhancing lesions seen on Sd and Td scans by 37% (p<0.001). Treatment effects on new enhancing lesions seen on Td scans was, on average, 28% higher than on those seen on Sd scans. The distribution of lesion sizes on Td scans changed significantly during the treatment period (p=0.05), due to a marked decrease in the number of small lesions. CONCLUSIONS: The effect of 44 microgram rh-IFN beta-1a in reducing multiple sclerosis disease activity, as monitored by Gd enhanced MRI, is not homogeneous, but graduated according to the pathological characteristics and size of the lesions.

Adult↗
PubMed1999

Interferon-beta-1a in relapsing-remitting multiple sclerosis: effect on hypointense lesion volume on T1 weighted images.

OBJECTIVE: Recently, a strong correlation between the increase in hypointense lesion load on T1 weighted spin echo images, and the increase in disability was reported. Although the effect of interferon-beta has been demonstrated both in reducing exacerbation rate, frequency of enhancing lesions, and accumulation of disease burden on T2 weighted images, the impact on the accumulation of hypointense lesions has not yet been evaluated. The aims of the present study were: (a) to assess for the first time the effect of interferon-beta-1a on T1 weighted MRI hypointense lesion volume; and (b) to evaluate the relation between changes on hypointense, hyperintense, and enhancing lesion volume before and during interferon-beta-1a treatment in relapsing-remitting multiple sclerosis. METHODS: After a baseline scan and 6 month pretreatment period, 67 patients with relapsing-remitting multiple sclerosis were treated with interferon-beta-1a by subcutaneous injection three times a week during a 12 month treatment period. All patients had MRI every month during the 6 month pretreatment period and for the first 9 months of the treatment period. A final MRI was also performed at the end of the 12 month treatment period. RESULTS: There was a significant increase in the mean hyperintense lesion volume during the pretreatment phase (6 months) and a slight decrease during the treatment period (12 months), whereas the hypointense lesion volume increased significantly before treatment and remained substantially stable during treatment. There was a significant correlation between changes in hypointense and hyperintense lesion volume during the observation period, but not during treatment. The monthly mean volume of Gadolinium-DTPA enhancing lesions was significantly higher during the pretreatment than the treatment period, and the enhancing lesion volume correlated with changes of hyperintense and hypointense lesion volumes only during the observation period. CONCLUSION: These data suggest that interferon-beta-1a has a stabilising effect on T1 weighted hypointense lesion volume.

Adult↗