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C Pozzilli

Publications and source records attributed to C Pozzilli.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1999

Interscanner variation in brain MR lesion load measurements in multiple sclerosis using conventional spin-echo, rapid relaxation-enhanced, and fast-FLAIR sequences.

BACKGROUND AND PURPOSE: Different MR pulse sequences have been proposed for measuring multiple sclerosis (MS)-related abnormalities. The reproducibility of measured brain MS lesion volumes was compared for MR images performed using different scanners and different pulse sequences. METHODS: Nine patients with relapsing-remitting MS were each imaged on two scanners and, on each occasion, dual-echo conventional spin-echo, dual-echo rapid-acquisition relaxation-enhanced (RARE), and fast fluid-attenuated inversion recovery (fast-FLAIR) images were obtained. The lesion volume present on each image was evaluated three times by a single observer in random order, using a local thresholding technique. RESULTS: The mean lesion volumes present on fast-FLAIR images were significantly higher than those measured on dual-echo conventional spin-echo and RARE images. The mean intraobserver coefficients of variation for the different sequences and scanners ranged from 3.0% to 4.2% (no statistically significant difference). For each of the sequences, the use of different scanners introduced a variability that was higher than the intraobserver variability: the interscanner coefficient of variation was 7.4% for conventional spin-echo, 9.5% for RARE, and 18.5% for fast-FLAIR images. CONCLUSION: Our study confirms that the use of different scanners significantly influences lesion loads measured from MR images of patients with MS and establishes that newer sequences are more susceptible to measurement variability. It also indicates that, if newer sequences are to be used in clinical trials, careful standardization is needed.

Adult↗
PubMed1998

Serum amyloid A protein is elevated in relapsing-remitting multiple sclerosis.

In multiple sclerosis (MS), the signs of inflammation that can be detected in the central nervous system are not mirrored by unequivocal markers of activation of the immune system in the periphery. We performed a serial monitoring of serum amyloid A protein (SAA), a major acute phase reactant, in peripheral blood of patients with relapsing-remitting MS over a 3-month period. Patients were monitored in parallel with gadolinium-enhanced magnetic resonance imaging (Gd-MRI) of the brain. The results show that signs of ongoing peripheral inflammation, reflected by elevations of SAA levels, can be detected in MS patients.

Adult↗
PubMed1998

A longitudinal brain MRI study comparing the sensitivities of the conventional and a newer approach for detecting active lesions in multiple sclerosis.

Monthly dual-echo spin-echo (SE) and enhanced magnetic resonance imaging (MRI) after the injection of a standard dose (SD) of gadolinium (Gd) is the conventional approach to monitor short-term disease activity in multiple sclerosis (MS). In this study, the sensitivity of this approach in detecting active lesions in MS was compared with that of monthly fast fluid attenuated inversion recovery (FLAIR) scans associated with enhanced MRI after the injection of a triple dose (TD) of Gd. Thirteen patients with relapsing-remitting MS entered the study. Monthly MRI scans were obtained on four occasions in two separate sessions (interval between 12 and 24 h). In one session, dual-echo conventional SE and SD Tl-weighted scans were obtained; in the other, fast-FLAIR and TD Tl-weighted scans. The order of the two sessions was randomized. Three observers counted the number of active lesions detected by each of the two approaches. One hundred and four active lesions were detected by the conventional approach and 199 by the newer approach (average increase per patient = 75%, range = 0-325%). The mean number of active lesions per month per patient was 2.0 for the conventional approach and 3.8 for the new approach (P = 0.004). Scans with active lesions were 34/52 (65%) with the conventional approach and 37/52 (71%) with the new approach. Our data indicate that the combined use of monthly fast-FLAIR and TD enhanced Tl-weighted scans increases the number of active lesions detected on serial MRI scans from patients with MS.

Adult↗
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↗