Biomedical subjects

C Pozzilli

Publications and source records attributed to C Pozzilli.

At least 19 recordsLinked to original sources

PubMed2001

Satellite potentials on EMG: neurophysiologic evidence of axonal transection in MS?

To detect signs of axonal damage in MS, the authors investigated the occurrence in EMG of motor unit action potentials with satellite potentials (SP-MUAP) in the upper limb muscles in 10 consecutive patients with MS with cervical spinal cord demyelinating lesions and 10 control subjects. Subjects' SP-MUAP rate was 0 to 2.5% (median 0%) in the control group, and 0 to 17.5% (median 7.5%) in the MS group (p < 0.01). Motor unit remodeling secondary to axonal transection of spinal motor neurons traversing cervical demyelinating lesions may be hypothesized.

Adult↗

PubMed2001

T(1) hypointense lesions in secondary progressive multiple sclerosis: effect of interferon beta-1b treatment.

Recently, the clinical efficacy of interferon beta-1b (IFNbeta-1b) was demonstrated for secondary progressive (SP) multiple sclerosis in a European multicentre study. We evaluated the effect of IFNbeta-1b treatment on the rate of development of hypointense T(1) MRI lesions, a putative marker of axonal damage. Unenhanced T(1)-weighted images were obtained in a subgroup of 95 multiple sclerosis patients from five centres at 6-month intervals; this subgroup was similar to the total study population for all demographic, clinical and MRI parameters. An experienced observer blinded to the clinical data and treatment allocation measured volumes. The median baseline lesion load for hypointense T(1) lesions was 5.1 cm(3) for placebo-treated and 4.9 cm(3) for IFNbeta-1b-treated patients (P = 0.56). Placebo-treated patients showed an increase in T(1) lesion load by a median of 14% per year (P = 0.0002 compared with baseline); this was reduced to 7.7% per year in the IFNbeta-1b-treated patients (P = 0.003 versus placebo). In the IFNbeta-1b arm there was a statistically significant correlation between absolute change in Expanded Disability Status Scale scores and T(1) lesion load by month 36 (r = 0.38, P = 0.0015). In patients with SP multiple sclerosis, IFNbeta-1b treatment reduces the development of hypointense T(1) lesions, suggesting that reduced axonal damage in lesions may play a part in the beneficial effect that is observed clinically.

Adult↗

PubMed2001

Patterns of cognitive impairment in secondary progressive stable phase of multiple sclerosis: correlations with MRI findings.

Cognitive impairment is commonly described in multiple sclerosis (MS), but conflicting results have been reported about its pattern by previous studies focused on heterogeneous patient groups. The aim of this study was to investigate the cognitive skills of a homogeneous group of secondary progressive MS patients, and to examine the relationship of this impairment to MRI parameters. Forty-four MS patients underwent a series of neuropsychological tests devised to explore the main cognitive domains, and T1- and T2-weighted brain MRI. Results showed the presence of deficits of attention, memory, planning abilities, problem-solving and conceptual reasoning (frontal functions) in a subgroup of MS patients. Correlations between the performance in some 'frontal' tests and the extent of frontal lobe MRI lesional area were present, but rather unspecific, the same performance being also correlated with the nonfrontal lesional area. These findings suggest that in MS, overall macroscopic and microscopic brain damage is more important than the corresponding focal brain disease, even in determining deficits of selective cognitive domains.

Adult↗

PubMed2001

Intra-observer, inter-observer and inter-scanner variations in brain MRI volume measurements in multiple sclerosis.

INTRODUCTION: Measurement of brain volume on magnetic resonance imaging (MRI) scans is regarded as an objective marker of multiple sclerosis (MS) severity with the potential to monitor treatment efficacy accurately. This study was performed to assess the variability of brain MRI volume measurements. PATIENTS AND METHODS: We studied nine patients with relapsing-remitting MS, who were imaged on two occasions (separated by an interval of 24 h) using two different MR scanners and fast fluid-attenuated inversion recovery (fast-FLAIR) sequences. The whole brain volume computed from each image was measured three times by three observers using a seed-growing technique based on signal intensity thresholding. Intra-observer, inter-observer and inter-scanner variabilities were expressed as coefficients of variations (COVs). The inter-scanner variability included not only the intra-observer variation but also the repositioning variability and the variation in observed brain volume caused by different scanner hardware and sequence implementations. RESULTS: There was no statistically significant difference in patients' brain volume values between observers (P=0.82) or between scanners (P=0.30). The mean intra-observer COV was 1.2% (s.e.=0.4%), the mean inter-observer COV was 1.8% (s.e.=0.8%) and the mean inter-scanner COV was 2.4% (s.e.=1.2%). The intra-observer variance was not statistically different from those found between observers (P=0.83) or scanners (P=0.44). CONCLUSION: The intra-observer variability in brain volume measurements found in this study was within the range of intra-observer variability found in previous studies. This study shows that the use of different observers and MR scanners has only a small influence on the measured brain volume and does not affect the reproducibility of this measurement greatly.

Adult↗

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↗