Biomedical subjects

C Pozzilli

Publications and source records attributed to C Pozzilli.

At least 37 records · Page 2Linked to original sources

PubMed2003

Longitudinal evaluation of depression and anxiety in patients with clinically isolated syndrome at high risk of developing early multiple sclerosis.

We investigated the relationship between emotional changes, brain lesion burden and development of multiple sclerosis (MS). Thirty-seven consecutive patients with clinically isolated syndrome (CIS) were prospectively assessed with the Expanded Disability Status Scale (EDSS), the 21-item Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI) and gadolinium enhanced (Gd+) MRI scans. BDI and STAI were also administered to 36 age-matched controls. Conversion to MS was defined as the occurrence of a clinical relapse. CIS patients were more likely to endorse symptoms of anxiety and depression than controls. Baseline scores for depression and anxiety did not correlate with the total lesion load (i.e., volume of Gd+, T2 and T1 lesions) and the number of Gd+ lesions during the first six months of follow-up. A positive correlation was found between severity of depressive scores and the lesion load in the right temporal region (P = 0.005). After 33+/-6 months of the study entry, patients who had a clinical relapse were more frequently depressed (P = 0.001) than those relapse free. Emotional disturbances are frequently observed in CIS patients and show a tendency towards a normalization in relapse-free patients. The increased rate of depressive symptoms observed in patients who developed MS seems to result from a combination of psychological and organic features. The lesion load in the right temporal region is confirmed as a key area for developing depressive symptoms, even in the early phase of the disease.

Adult↗

PubMed2003

Oral interferon beta-1a in relapsing-remitting multiple sclerosis: a double-blind randomized study.

BACKGROUND: Interferon beta (IFNB) is available in parenteral formulations for treatment of multiple sclerosis (MS). The purpose of this study was to evaluate safety, tolerability and effects on MRI lesions of three different doses of oral IFNB-1a compared with placebo over six months in relapsing-remitting (RR) MS patients. METHODS: In this multicenter; double-blind randomized trial, RR-MS patients received 0.06, 0.6 or 6 million international units (MIU) IFNB-1a or placebo every other day for up to six months. Gadolinium DTPA-enhanced brain MRI scans were performed at screening and monthly during treatment. The primary variable was the cumulative number of newly active lesions. Secondary variables included volume of enhancing lesions on T1-weighted images each month and lesion volume on T2-weighted images at months three and six. Safety measures included adverse events, laboratory variables, vital signs, ECG, physical examination, EDSS and number of relapses. Neopterin was measured in 21 patients and neutralizing antibodies in 24 patients. RESULTS: Of 194 screened patients, 173 were randomized (42-44 patients per group) in 15 centers. Median cumulative numbers of newly active lesions over six months were 4.0 in the placebo and 0.6 MIU groups, compared with 7.5 and 9.0 in the 0.06 and 6 MIU groups (no significant differences). Secondary efficacy endpoints showed small and inconsistent differences between groups. Adverse events showed no notable group differences. Approximately two-thirds of patients in each group remained relapse free. No patients showed neutralizing antibodies. Neopterin levels were comparable between groups. CONCLUSION: Oral IFNB-1a showed neither beneficial effects in RRMS nor any systemic biological effects. Treatment was safe and well tolerated.

Adjuvants, Immunologic↗

PubMed2002

A one-year study on the pharmacodynamic profile of interferon-beta1a in MS.

Interferon (IFN)-beta1a induction of neopterin and beta2-microglobulin (beta2-MG) were evaluated over 1 year in patients with MS. Neopterin and beta2-MG levels peaked 24 to 48 hours after weekly injections of IFNbeta1a over the entire study period. Predose levels of neopterin decreased significantly, consistent with a long-term decrease in IFNgamma expression and macrophage activation during IFNbeta-1a treatment. Predose levels of beta2-MG increased, the significance of which is as yet unclear.

Adult↗

PubMed2002

Blood cholesterol and MRI activity in first clinical episode suggestive of multiple sclerosis.

OBJECTIVES: The present study was planned to investigate the relationship between the plasma lipid profile and disease activity in patients with a first clinical episode suggestive of multiple sclerosis (MS). MATERIAL AND METHODS: Eighteen consecutive out-patients underwent a monthly brain magnetic resonance imaging (MRI), blood sample and neurological assessment over 6 months. Blood samples were used to evaluate total cholesterol and triglyceride levels as well as their lipoprotein fractions. Plasma total apolipoprotein E concentration was also determined. RESULTS: We found a significant correlation between the mean number of enhancing lesions and the mean plasma level of both total and low density lipoprotein cholesterol. The total plasma cholesterol level increased on average by 4.4 mg/dl for each enhancing lesion. CONCLUSION: Our preliminary data suggest a potential role of plasma cholesterol level as a biological marker of disease activity after a first demyelinating event. Further studies need, however, to be designed to determine whether the plasma cholesterol level is of practical use in monitoring the disease course.

Acute Disease↗

PubMed2002

A 6-year clinical and MRI follow-up study of patients with relapsing-remitting multiple sclerosis treated with Interferon-beta.

There are few long-term clinical and magnetic resonance imaging (MRI) data on patients treated with interferon-beta (IFN-beta) for relapsing-remitting multiple sclerosis (RRMS). The aim of this study was to provide clinical and MRI data on 68 patients with RRMS treated over a 6-year period and to investigate whether a baseline MRI predicts their long-term clinical and MRI outcome. Six MRI scans were performed monthly before treatment and a further 13 scans were performed during treatment with IFN-beta, the last of which 6 years after commencement of treatment. The relapse rate, disability as measured by the Expanded Disability Status Scale (EDSS), and MRI parameters, including Gd-enhancing lesion load (Gd-LL), T2 hyperintense lesion load (T2-LL) T1 hypointense lesion load (T1-LL) and supratentorial brain volume (SBV) were measured throughout the study. The mean annual relapse rate over the 6 years was 0.52 (SD 0.67), which is significantly lower (68.6%) than the mean annual relapse rate of 1.6 observed during the 2-year period before the commencement of treatment (P < 0.01). The median EDSS score increased from 2 to 2.5, remaining stable in 60% of the patients. From the baseline scan to the final scan, there was a median increase of 7% in the T2-LL and 23.9% in the T1-LL, whilst SBV decreased by 2.7%. The increase in the EDSS over the course of the study was significantly correlated with a reduction in brain volume (r = 0.46, P = 0.001). Greater brain damage at baseline, as measured by both T2-LL and T1-LL, was significantly associated with an increase in disability over the 6 years (r = 0.44, P = 0.0009; r = 0.50, P = 0.0007, respectively). This study shows a sustained effect of IFN-beta on the relapse rate, which is lower than during the 2 years before treatment commencement. More than half the patients showed an improvement or stabilization in the EDSS score. The increment in disability was correlated with the development of brain atrophy but not with increases in lesion burden. Finally, the finding that the extent of lesion burden at the baseline was a strong predictor of increasing disability suggests that IFN-beta treatment might have a moderate effect in modifying the multiple sclerosis (MS) disease course over 6 years unless preventive treatment is started early.

Adjuvants, Immunologic↗

PubMed2002

Home based management in multiple sclerosis: results of a randomised controlled trial.

BACKGROUND: Home based medical care is a popular alternative to standard hospital care but there is uncertainty about its cost-effectiveness. OBJECTIVES: To compare the effectiveness and the costs of multidisciplinary home based care in multiple sclerosis with hospital care in a prospective randomised controlled trial with a one year follow up. METHODS: 201 patients with clinically definite multiple sclerosis were studied. They were randomised in a ratio 2:1 to an intervention group (133) or a control group (68). They were assessed at baseline and one year after randomisation with validated measures of physical and psychological impairment and quality of life (SF-36 health survey). The costs to the National Health Service over the one year follow up were calculated by a cost minimisation analysis. RESULTS: There were no differences in functional status between the home based care group and the hospital group. There was a significant difference between the two groups favouring home based management in four SF-36 health dimensions-general health, bodily pain, role-emotional, and social functioning (all p < or = 0.001). The cost of home based care was slightly less (822 euros/patient/year) than hospital care, mainly as a result of a reduction in hospital admissions. CONCLUSIONS: Comprehensive planning of home based intervention implemented by an interdisciplinary team and designed specifically for people with multiple sclerosis may provide a cost-effective approach to management and improve the quality of life.

Adult↗

PubMed2002

Prospective study of multiple sclerosis with early onset.

Fifty-four subjects (36 females and 18 males) affected by clinically definite multiple sclerosis (MS) and with onset of the disease at 15 years of age or before were prospectively studied in five Italian MS centres. Female/male ratio was 4.7 in subjects with age > or = 12 years, suggesting a role of hormonal changes in triggering MS onset The mean follow-up duration was 10.9+/-5.6 years. The functional systems more frequently involved at onset were the pyramidal and brainstem (both in 28% of cases). The onset was monosymptomatic in 31 subjects (57%). The course was relapsing-remitting in 39 subjects (72%) and relapsing-progressive in 15 (28%). Disability was assessed by the Expanded Disability Status Scale (EDSS): the mean score after 8 years of follow up was 3.5 (+/-2.5). The score was <4 in 68% of cases, between 4 and 6 in 8% of cases, >6 in 24% of cases. Disability after 8 years was highly predicted by disability in the first year (p=0.008). There was a tendency to a worse prognosis in relation to the number of relapses in the first 2 years (p=0.08). The outcome was not influenced by the characteristics of symptoms at onset age and gender.

Adolescent↗

PubMed2002

MRI brain volume changes in relapsing-remitting multiple sclerosis patients treated with interferon beta-1a.

The aim of this study was to investigate changes of brain volume as measured by magnetic resonance imaging (MRI) in relapsing-remitting multiple sclerosis (MS) patients under treatment with interferon beta-1a. Moreover, the relationship between brain volume changes and standard MR or clinical outcome variables was determined. After a 6-month pretreatment period, 52 patients with relapsing-remitting MS were assigned to receive interferon beta-1a (Rebif-Serono) during a 24-month treatment period MRI scans were performed monthly during the 6-month pretreatment period and for the first 9 months of the treatment period. A final MRI scan was also performed at the end of the 12- and 24-month treatment period. Over 24 months of IFNbeta-1a treatment, a significant decrease of hyperintense lesion volume was found (-18.0%; p<0.0001) compared to the last pretreatment scan, while T1 hypointense volume showed a slight nonsignificant increase (+2.2%), and brain volume showed a significant decrease (-2.2%; p<0.0001). The mean volume of enhancing lesions over the 6-month pretreatment period was significantly related to absolute (p=0.02; r=-0.32) and per cent change (p=0.03; r=-0.30) of brain volume during 24-month treatment period. No correlations between changes in brain volume and changes in T2 hyperintense volume or T1 hypointense volume were observed. Neither was there a relationship between brain volume and changes of Expanded Disability Status Scale (EDSS) or frequency in clinical relapses. Of the group in whom was detected a significant decrease of brain volume, 13 out of 26 (50%) had a sustained change in EDSS while in the group that did not have a significant decrease of brain volume, only 3 out of 26 (11.5%) had a sustained EDSS change (p=0.02). In this study a decrease of brain volume was found in relapsing-remitting MS patients treated with IFNbeta-1a over 2 years. The only parameter that predicted brain volume decrease by 2 years of IFNbeta-1a treatment was the mean volume of enhancing lesions over the 6-month pretreatment period.

Adolescent↗

PubMed2001

The effect of IFNbeta-1b on the evolution of enhancing lesions in secondary progressive MS.

BACKGROUND: After the resolution of contrast enhancement, the majority of new MS lesions become isointense with surrounding white matter on T1-weighted MRI. Less commonly, a hypointense T1 lesion develops, representing the development of more severe focal tissue damage. Interferon beta (IFNbeta) reduces both the number of new enhancing lesions and the duration of contrast enhancement. OBJECTIVE: To determine if IFNbeta affects the degree of tissue damage within new lesions and if its effects are related to lesion size. METHODS: One hundred twenty-five patients with secondary progressive MS from seven European sites were randomized to receive either IFNbeta-1b or placebo. Monthly, contrast-enhanced T1-weighted MR images were acquired at baseline, at months 1 to 6, and at months 19 to 24. The size of all new enhancing lesions developing between months 1 and 6 was recorded and their appearance at follow-up documented. RESULTS: In the first 6 months, fewer new enhancing lesions occurred in the IFNbeta-1b arm. This difference was greater for small (70% decrease) than for large (46% decrease) lesions. Hypointense T1 lesions were more likely to form from large (25%) than from small (9%) enhancing lesions in both treatment arms. Patients taking IFNbeta-1b developed fewer hypointense T1 lesions; however, the proportion of enhancing lesions developing into hypointense T1 lesions was similar in both arms. CONCLUSION: IFNbeta-1b reduced the number of new enhancing lesions, with a greater effect on small lesions. However, when a new enhancing lesion did become established, treatment with IFNbeta-1b did not alter its subsequent course.

Adult↗

PubMed2001

Clinical-MRI correlations in a European trial of interferon beta-1b in secondary progressive MS.

BACKGROUND: The recently completed placebo-controlled multicenter randomized trial of interferon beta-1b (Betaferon) in 718 patients with secondary progressive MS shows significant delay of disease progression and reduction of relapse rate. This study provides an opportunity to assess the level of relationship between clinical and MRI outcomes in this cohort of patients with secondary progressive MS. METHODS: Brain T2-weighted lesion volume was measured annually in all available patients, with visual analysis to identify any new or enlarging (active) T2 lesions at each annual time point. A subgroup of 125 patients had monthly gadolinium-enhanced, T1-weighted imaging at months 0 to 6 and 18 to 24. Relapses were documented and expanded disability status scale (EDSS) was measured every 3 months. RESULTS: For the annual MRI outcomes, a significant but modest correlation was identified between the change in T2 lesion volume from baseline to the final scan and the corresponding change from baseline in EDSS (r = 0.17, p < 0.0001). There were significant correlations between the cumulative number of active T2 lesions and 1) change in EDSS (r = 0.18, p < 0.0001) and 2) relapse rate (r = 0.24, p < 0.0001). In the subgroup of 125 patients undergoing monthly imaging, MRI lesion activity was correlated with relapse rate over months 0 to 24 (r = 0.24, p = 0.006) but not with change in EDSS. CONCLUSIONS: These results confirm that the clinical-MRI relationships previously identified in relapsing-remitting MS still are apparent in the secondary progressive phase of the disease and support the use of MRI as a relevant outcome measure. In view of the relatively modest nature of the correlations, it seems unwise to rely on such MRI measures alone as primary efficacy variables in secondary progressive MS trials.

Brain↗

PubMed2001

Final analysis of the European multicenter trial on IFNbeta-1b in secondary-progressive MS.

BACKGROUND: Based on a prospectively planned interim analysis, the European study of interferon beta-1b (IFNbeta-1b) provided evidence that the treatment delays neurologic deterioration in patients with secondary progressive MS (SPMS). The authors analyzed all data collected until closure of the double-blind study to further scrutinize the consistency of the findings. METHODS: The multicenter, double-blind, randomized, placebo-controlled trial treated patients for up to 36 months. The primary and all secondary endpoints of this study were evaluated using the data set at study termination, with a mean follow-up under double-blind conditions of 1054 +/- 199 and 1068 +/- 176 days for the placebo and IFNbeta-1b group. Alternative and more demanding definitions of disease progression were explored. Confirmed progression was analyzed in subgroups according to baseline demographics and baseline indicators of disease activity. RESULTS: Forty-eight of 358 placebo and 40 of 360 IFNbeta-1b-allocated patients were lost to follow-up. Time to confirmed 1.0-point Expanded Disability Status Scale (EDSS) progression for patients receiving IFNbeta-1b was delayed (p = 0.007). The proportion of patients with a confirmed 2.0-point EDSS progression was approximately 27% lower for the group treated with IFNbeta-1b, both including and excluding EDSS data collected during relapses. The proportion of patients with either progression or relapses decreased by nearly 30% in patients treated with IFNbeta-1b compared with placebo. Analysis of subgroups suggests that patients with higher prestudy disease activity (more than two relapses or EDSS progression by more than 1.0 point or both) seem to have a more pronounced treatment effect. CONCLUSION: Analysis of the data set at study termination including additional post hoc outcome measures is consistent with the original findings, thus supporting the conclusion that treatment with IFNbeta-1b is effective in patients with SPMS fulfilling the inclusion criteria of this study.

Adjuvants, Immunologic↗

PubMed2001

Interferon-beta1b in the treatment of secondary progressive MS: impact on quality of life.

BACKGROUND: The recent randomized, controlled trial of interferon-beta1b (IFN-beta1b) in 718 patients with secondary progressive MS (SP-MS) demonstrated a significant effect on the development of disability as evaluated by the physician. Its effect on patient-reported health-related quality of life (HrQoL) is reported herein. METHODS: In this multicenter, double-blind, randomized, placebo-controlled trial, outpatients with SP-MS scoring between 3.0 and 6.5 on the Expanded Disability Status Scale received either 8 x 10(6) IU of IFN-beta1b or placebo for up to 3 years. A range of outcomes was measured, including HrQoL, which was assessed using the Sickness Impact Profile (SIP), a self-report questionnaire validated for use in MS. Measurements were undertaken at baseline and at 6-monthly intervals thereafter for 36 months. RESULTS: A slight positive effect on the HrQoL of the IFN group in comparison with the placebo group was found, which reached significance in the physical scale of the SIP at 6 and 12 months and at last visit. There was moderate correlation between physician-assessed evaluation of change and patient-reported change. CONCLUSIONS: IFN-beta1b may delay sustained deterioration in patient-reported HrQoL in SP-MS. Methods of interpreting change in HrQoL are currently insufficiently developed to determine how clinically important these changes are for this population.

Activities of Daily Living↗

PubMed2001

Sample size estimations for MRI-monitored trials of MS comparing new vs standard treatments.

The authors estimated the sample sizes needed for exploratory trials of MS assessing the efficacy of new treatments in reducing the number of new enhancing lesions vs those of interferon-beta or glatiramer acetate. The sample sizes per arm ranged from 868 (effect: 20%) to 94 (effect: 50%) for patients with relapsing-remitting MS and from 2,484 (effect: 20%) to 361 (effect: 50%) for patients with secondary progressive MS. In MS, exploratory trials of new vs available therapies require large numbers of patients, even when MR end-points are used.

Adjuvants, Immunologic↗

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↗

PubMed2001

Fatigue in progressive multiple sclerosis: results of a randomized, double-blind, placebo-controlled, crossover trial of oral 4-aminopyridine.

Previous studies suggest that aminopyridine may play a role in the symptomatic treatment of fatigue in multiple sclerosis. Although the mechanism underlying the beneficial effect on fatigue remains unclear, it has been proposed that aminopyridines may help to improve conduction in demyelinated central pathways, implicating both axonal and synaptic mechanisms. The objective of the present study is to determine whether 4-AP decreases daily-living fatigue in progressive multiple sclerosis. The effect of 4-AP on other neurophysiological and neuropsychological parameters was also considered. A 'double-blind', randomized, 'placebo-controlled', crossover trial was conducted on 54 patients with progressive multiple sclerosis. All patients received treatment with placebo and 32 mg per day of 4-AP, each for 6 months. The main outcome measure was the Fatigue Severity Scale. Secondary measures were EDSS, cognitive functions and neurophysiological parameters. Forty-nine patients (91%) completed the study. Changes in fatigue scores, EDSS and cognitive functions were not significantly different between 4-AP and placebo. However, when patients treated with 4-AP were divided into two groups according to the serum level of 4-AP, a significant effect on fatigue compared with placebo was observed in the 'high level' (>30 ng/ml) group (P=0.05). Synchronization of motor evoked potentials improved during 4-AP with respect to placebo (P=0.019) and this correlated positively with fatigue reduction (P=0.010). No relevant side effects were observed.

4-Aminopyridine↗