Biomedical subjects

M Filippi

Publications and source records attributed to M Filippi.

At least 37 records · Page 2Linked to original sources

PubMed2005

Evidence for progressive gray matter loss in patients with relapsing-remitting MS.

Little is known about the temporal evolution of gray matter damage occurring early in the course of multiple sclerosis (MS). The authors investigated the evolution of gray matter volume loss in 117 patients with relapsing-remitting MS, scanned monthly for a 9-month period. Time-trend analysis revealed a decrease of gray matter volumes over the study period (p < 0.001). This study shows that gray matter damage in relapsing-remitting MS evolves markedly over a short period of observation.

Adult↗

PubMed2005

Long-term clinical outcome of primary progressive MS: predictive value of clinical and MRI data.

The authors sought to identify clinical and MRI predictors of outcome in primary progressive multiple sclerosis (PPMS). Clinical and MRI assessments were performed at baseline and 2 and 5 years (clinical only). At baseline, disease duration, expanded disability status scale (EDSS) and brain volume predicted outcome. Adding short-term change variables, baseline EDSS, changes in T2* lesion load and cord area, and number of new lesions were predictive. Clinical and MRI variables predict long-term outcome in PPMS.

Atrophy↗

PubMed2005

A longitudinal study of cognition in primary progressive multiple sclerosis.

There are few longitudinal studies of cognition in patients with multiple sclerosis, and the results of these studies remain inconclusive. No serial neuropsychological data of an exclusively primary progressive series are available. Cross-sectional analyses have revealed significant correlations between cognition and magnetic resonance imaging (MRI) parameters in primary progressive multiple sclerosis (PPMS). This study investigated cognitive and MRI change in 99 PPMS patients from five European centres for 2 years. They were assessed at 12 month intervals using the Brief Repeatable Battery, a reasoning test, and a measure of depression. The MRI parameters of T1 hypointensity load, T2 lesion load, and partial brain volume were also calculated at each time point. There were no significant differences between the mean cognitive scores of the patients at year 0 and year 2. However, one-third of the patients demonstrated absolute cognitive decline on individual test scores. Results indicated that initial cognitive status on entry into the study was a good predictor of cognitive ability at 2 years. There was only a small number of significant correlations between changes in cognition and changes on MRI, notably T1 hypointensity load with the two attentional tasks (r = -0.266, P = 0.017; r = -0.303, P = 0.012). It is probable that multiple factors underlie this weak relation between the cognitive and MRI measures.

Adult↗

PubMed2005

A whole brain MR spectroscopy study from patients with Alzheimer's disease and mild cognitive impairment.

Brain damage in Alzheimer's disease (AD) and mild cognitive impairment (MCI) is widespread with involvement of large portions of the neocortex and the subcortical white matter. A quantitative measure of neuronal damage of the entire brain might be valuable in the context of large-scale, longitudinal studies of these patients. This study investigated the extent of neuroaxonal injury of patients with AD and MCI using a novel unlocalized proton magnetic resonance spectroscopy ((1)H-MRS) technique, which allows quantification of the concentration of N-acetylaspartate from the whole of the brain tissue (WBNAA). Conventional brain MRI and WBNAA were obtained from 28 AD patients, 27 MCI patients and 25 age-matched controls. Normalized brain volume (NBV) was also measured using an automated segmentation technique. WBNAA and NBV showed a significant heterogeneity between groups (P < 0.001). WBNAA concentration was different between controls and MCI patients (P = 0.003), but not between MCI and AD patients (P = 0.33). NBV differed both between controls and MCI patients (P = 0.02) and between MCI and AD patients (P = 0.03). A multivariate regression model retained WBNAA as the best MRI predictor of the Mini Mental State Examination score (P = 0.001). Significant neuronal damage, which is related to the extent of cognitive decline, can be quantified in the whole brain tissue of patients with AD, using a novel (1)H-MRS approach. The demonstration in patients with MCI of MR structural and metabolic findings, intermediate between those of healthy volunteers and those of AD patients, indicates that neuronal damage is already evident and widespread in individuals with MCI before they are clinically demented.

Aged↗

PubMed2005

Movement preparation is affected by tissue damage in multiple sclerosis: evidence from EEG event-related desynchronization.

OBJECTIVE: To investigate the impact of brain tissue damage in Multiple Sclerosis (MS) on the efficiency of programming of voluntary movement, assessed using event-related desynchronization of the EEG. METHODS: The onset latency of mu ERD (percent desyncronization of the mu rhythm preceding movement onset) to hand movement was studied in 34 MS patients. ERD onset was compared with normative data and correlated with T1 and T2 total lesion volume (TLV) at magnetic resonance imaging (MRI). RESULTS: ERD onset latency was significantly correlated with T1-TLV (r = 0.53, P = 0.001) and T2 lesion load (r = 0.5, P = 0.003), even after correcting for disability. Patients with higher T1-TLV had significantly delayed ERD onset compared with normal subjects and with patients with lower T1-TLV; patients with higher T2-TLV had significantly delayed ERD compared with normal subjects only. ERD onset latency was not correlated to clinical disability. CONCLUSIONS: Our finding of delayed ERD onset in patients with more severe measures of brain damage, independently from clinical disability, suggests that functional cortico-cortical and cortico-subcortical connections underlying the expression of ERD during programming of voluntary movement are disrupted by the MS related pathological process. Further, studies are needed to evaluate the role of specific anatomical cortico-subcortical circuits in determining this abnormality. SIGNIFICANCE: The extent of brain lesion load in multiple sclerosis affects cortical changes related to motor preparation, detected by analysis of onset latency of event-related desynchronization (ERD) of the mu rhythm to self-paced movement.

Adult↗

PubMed2005

A method for obtaining tract-specific diffusion tensor MRI measurements in the presence of disease: application to patients with clinically isolated syndromes suggestive of multiple sclerosis.

The aim of this study was to investigate whether neurological symptoms related to a specific axonal fiber tract in brain white matter were associated with a higher degree of tissue damage in that region, in patients at presentation with clinically isolated syndromes (CIS) suggestive of multiple sclerosis. To this end, a magnetic resonance imaging (MRI) method to segment and evaluate the fiber bundle of interest was implemented, taking care to circumvent the problems caused by pathology. Diffusion tensor (DT) MRI tractography was used to construct, from healthy volunteer data, a probability map for the pyramidal tract (PYT), and this map was applied to patients to calculate DT-derived metrics inside the PYT. In CIS patients with clinical symptoms related to motor function, the DT-derived mean diffusivity and the lesion volume in the PYT were found to be increased, while the fractional anisotropy was no different, when compared to those patients without motor symptoms. These results may be explained by several microstructural changes in the damaged tissue, such as changes in the permeability of axonal cell membranes, decreases of axonal density and edema. The approach taken to analyze a specific fiber tract was possible because the axons in the tract have a high orientational coherence, allowing tissue structure changes to be isolated from the tissue architecture. Its extension to other white matter fiber bundles is therefore limited to bundles with high orientational coherence.

Adult↗

PubMed2005

Quantification of cervical cord pathology in primary progressive MS using diffusion tensor MRI.

OBJECTIVE: To investigate the extent and severity of cervical cord damage using diffusion tensor MRI (DT-MRI) and histogram analysis in patients with primary progressive MS (PPMS). METHODS: Diffusion-weighted sensitivity-encoded (SENSE) echoplanar images of the cervical cord and brain dual-echo and diffusion-weighted scans were acquired from 24 patients with PPMS and 13 healthy controls. Cord and brain mean diffusivity and fractional anisotropy histograms were produced. An analysis of variance model, adjusting for cord volume, was used to compare cord DT-MRI parameters from controls and patients. RESULTS: Compared to healthy controls, PPMS patients had reduced cervical cord cross-sectional area and average cord fractional anisotropy (p = 0.007), and increased cord mean diffusivity (p = 0.024). No correlations were found between DT-MRI metrics of the cord and quantities obtained from conventional and DT-MRI of the brain. CONCLUSIONS: DT-MRI of the cervical cord can quantify the extent of diffuse cord pathology in patients with PPMS. Such cord diffusivity changes in patients with PPMS are likely to reflect irreversible axonal injury and reactive gliosis and seem to be independent of brain damage.

Adult↗

PubMed2005

Characterizing the mechanisms of progression in multiple sclerosis: evidence and new hypotheses for future directions.

Major advancements have been achieved in our ability to diagnose multiple sclerosis (MS) and to commence treatment intervention with agents that can favorably affect the disease course. Although MS exacerbations and the emergence of disability constitute the more conspicuous aspects of the disease process, evidence has confirmed that most of the disease occurs on a constitutive and occult basis. Disease-modifying therapies appear to be modest in the magnitude of their treatment effects, particularly in the progressive stage of the disease. Therapeutic strategies currently used for MS primarily target the inflammatory cascade. Several potential mechanisms appear to be involved in the progression of MS. Characterizing these mechanisms will result in a better understanding of the various forms of the disorder and how to effectively treat its clinical manifestations. It is our objective within this 2-part series on progression in MS to offer both evidence-based observations and hypothesis-driven expert perspectives on what constitutes the cause of progression in MS. We have chosen areas of inquiry that appear to have been most productive in helping us to better conceptualize the landscape of what MS looks like pathologically, immunologically, neuroscientifically, radiographically, and genetically. We have attempted to advance hypotheses focused on a deeper understanding of what contributes to the progression of this illness and to illustrate new technical capabilities that are catalyzing novel research initiatives targeted at achieving a more complete understanding of progression in MS.

Disease Progression↗

PubMed2005

Intense immunosuppression followed by autologous stem cell transplantation in severe multiple sclerosis.

Aggressive forms of multiple sclerosis (MS) represent a limited group of demyelinating diseases that rapidly progress to severe disability. Currently available therapies are poorly effective against these clinical entities. Recently, it has been demonstrated that intense immunosuppression followed by autologous haematopoietic stem cell transplantation (AHSCT) can affect the clinical course of individuals with severe MS and completely abrogate the inflammatory activity detected by MRI. We report the result of the Italian phase 2 GITMO study, a multicentre study in which 21 MS patients, who were rapidly deteriorating and not responding to the usual therapeutic strategies, were treated with this procedure. The clinical effect of the treatment is long lasting, with a striking abrogation of inflammation detected by MRI findings. These results support a role for intense immunosuppression followed by ASCT as treatment in rapidly evolving MS cases unresponsive to conventional therapies.

Adult↗

PubMed2005

Defining the response to multiple sclerosis treatment: the role of conventional magnetic resonance imaging.

During the last two decades, conventional MRI (cMRI) has been extensively used in the diagnostic workup of multiple sclerosis (MS) patients, to monitor the natural history of the disease and to evaluate the efficacy of experimental treatments in randomised, controlled clinical trials. In the latter context, a major issue is represented by the high intra- and inter-individual heterogeneity of the MS patterns of disease activity and evolution. Such heterogeneity might explain, at least partially, the weak correlations found between clinical and cMRI aspects in patients with established MS, which is particularly evident when individual patients are considered. As a consequence, the definition of response to MS treatment, when based upon cMRI aspects, is still a challenging task. Although the use of cMRI-derived quantities as a standalone approach to define treatment options and strategies at an individual patient level should be discouraged, an evidence-based integration of clinical and cMRI data might be helpful in selected cases for an optimal work-up of patients undergoing immunomodulating or immunosuppressive treatments.

Evidence-Based Medicine↗

PubMed2005

Imaging spinal cord damage in multiple sclerosis.

During the past 2 decades, the considerable improvement of magnetic resonance (MR) technology and the development of new MR strategies capable of providing an in vivo overall assessment of multiple sclerosis (MS) pathology have allowed us to obtain important novel pieces of information on disease evolution in the brain. However, despite this, the correlation between brain MR imaging metrics and clinical disability are still suboptimal. A reason for this discrepancy might be the involvement of clinically eloquent structures, such as the spinal cord, which owing to technical challenges have not been extensively studied using MR imaging until very recently. An objective and accurate estimate of the presence and extent of spinal cord damage might indeed contribute to increasing the strength of the correlations between clinical and MRI metrics. This review summarizes the main results obtained from the application of conventional and modern MR-based techniques for the evaluation of spinal cord damage in MS.

Diffusion Magnetic Resonance Imaging↗

PubMed2005

The distribution of the magnetic resonance imaging response to glatiramer acetate in multiple sclerosis.

We investigated the distribution of the magnetic resonance imaging (MRI)-measured response to glatiramer acetate (GA) treatment in multiple sclerosis (MS) using data from a clinical trial of relapsing-remitting (RR) MS. A fixed and a random effects model were used to quantify the between-patient heterogeneity in treatment response, expressed as new enhancing lesion percentage reduction. In 95% of the patients, lesion reduction due to treatment was estimated to range between -20% and -54%, indicating a rather homogeneous effect of GA on MRI-measured disease activity in RRMS.

Brain↗

PubMed2005

Serum MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in multiple sclerosis: relationships with different magnetic resonance imaging measures of disease activity during IFN-beta-1a treatment.

Matrix metalloproteinase-9 (MMP-9) is involved in blood-brain barrier (BBB) disruption in active multiple sclerosis (MS), while MMP-2 seems to be associated with the chronic progressive phase of the disease. Recombinant interferon beta-1a (rIFNbeta-1a) is effective in restoring the BBB. We studied the relationships between serum MMP-9, MMP-2, TIMP-1 and TIMP-2 and different magnetic resonance imaging (MRI) measures of disease activity in MS patients during treatment with rIFNbeta-1a. Twenty-one relapsing-remitting (RR) MS patients underwent longitudinally simultaneous blood withdrawals and MRI (before and after standard dose (SD) and triple dose (TD) of gadolinium (Gd)) examinations before and during 48 weeks of rIFNbeta-1a (Rebif 22 mcg three times a week) treatment. Serum MMP-9, MMP-2, TIMP-1 and TIMP-2 were measured, MMP-9 to TIMP-1 and MMP-2 to TIMP-2 ratios were calculated and the numbers of Gd-SD, Gd-TD, new-Gd-SD, new-Gd-TD and new-T2 lesions counted. Serum MMP-9/TIMP-1 ratio (P < 0.0001), as well as the numbers of 'active' lesions (P ranging from 0.0004 to 0.005) decreased during treatment Moreover, serum MMP-9/TIMP-1 ratio proved to be a good positive predictor (estimate = 0.85; P < 0.05) of the numbers of MRI Gd-TD active lesions. These data confirm that serum MMP-9/TMIP-1 ratio may be viewed as a reliable marker and may be predictive of MRI activity in RR MS.

Adjuvants, Immunologic↗

PubMed2005

MRI results from the European Study on Intravenous Immunoglobulin in Secondary Progressive Multiple Sclerosis (ESIMS).

BACKGROUND: Monthly application of high-dose intravenous immunoglobulin (IVIG) to patients with secondary progressive multiple sclerosis (MS) showed no clinical benefit in the European Study on Immunoglobulin in MS (ESIMS). Magnetic resonance imaging (MRI) results may provide insights into the morphologic consequences of such treatment. METHODS: A total of 318 patients (mean age 44 +/- 7 years) were enrolled in 31 European and Canadian centres and treated monthly with 1 g/kg body weight of IVIG or equivalent amounts of albumin 0.1% for 27 months. MRI was performed at baseline and after 12 and 24 months and comprised of conventional dual-echo T2-weighted and T1-weighted scans before and after application of 0.1 mmol/kg Gd-DTPA. RESULTS: Similar to clinical variables, MRI measures at baseline were well comparable between treatment groups except for a somewhat lower mean number of contrast-enhancing lesions and number of active scans in IVIG-treated patients. Over the trial period there was almost no change of the T2-lesion load and the 'black hole' volume in both treatment groups and the cumulative number of contrast-enhancing lesions were similar. There was only a trend for fewer new or enlarged T2-lesions in IVIG patients, which disappeared after correction for the imbalance in the number of contrast-enhancing lesions at baseline. Brain volume in terms of a partial cerebral fraction decreased significantly less with IVIG than placebo treatment (final visit: -0.62 -/+ 0.88% versus -0.88 +/- 0.91%; P=0.009). This difference remained statistically significant with correction for active lesions at baseline (P=0.02) and was seen primarily in male patients and those with an Expanded Disability Status Scale score > or = 6 and no relapses in the two years before the study. CONCLUSION: The absence of significant differences in conventional MRI measures between both treatment groups parallels the negative clinical results of ESIMS. The causes for and possible long-term clinical effects of a lower rate of brain volume loss in IVIG patients should be explored further.

Adult↗

PubMed2005

Imaging the optic nerve in multiple sclerosis.

Although multiple sclerosis (MS) frequently involves the optic nerves, imaging this structure is not yet performed routinely in clinical practice. The recent improvement of magnetic resonance (MR) technology and the development of new MR strategies, capable of providing an, in vivo, overall assessment of MS pathology has allowed objective metrics to be obtained for monitoring disease evolution, essentially in the brain. However, despite this progress, the correlation between brain MR metrics of the disease and clinical disability are still disappointing. An objective and accurate estimate of the presence and extent of optic nerve involvement might help to overcome this clinical/MRI paradox. This review summarizes the main results obtained from the application of conventional and modern MR-based techniques for the evaluation of optic nerve damage in MS.

Atrophy↗

PubMed2005

[Occupational mortality in Italy during 1992, assessed through record-linkage between pension records and death certificates].

BACKGROUND: The creation of a surveillance system of occupational mortality in Italy is limited by the low quality of information on occupation in death certificates, since the information is often incomplete or lacking and because only the occupation at the time of death is registered. OBJECTIVE: To evaluate the possible use of INPS (National Institute of Social Security) records for the purpose of surveillance of occupational mortality, in terms of feasibility of setting up a system and of validity of the results obtained. METHODS: Death records of 218,510 subjects aged 18-74, deceased in the 12 months following the 1991 census, were obtained from ISTAT (Central Statistics Institute). These were combined through record-linkage with the INPS social security archives, which contain the employment records by economic sector going back to 1974, in order to assign these deaths the sector in which they had worked the longest. Mortality by specific causes was evaluated by industry by means of a proportional mortality analysis stratified by sex and occupational status, and adjusted for age, education, marital status, geographical area of birth, drawing a disability pension, employment status at the time of death and work instability. RESULTS: Record-linkage allowed attribution of the longest held job to 70% of the deaths recorded. Results are presented and discussed only on mortality in men due to asbestosis and silicosis, and causes of death with a substantial proportion attributable to occupation: chronic obstructive pulmonary disease (COPD); cancers of the bladder, nasal cavity, larynx, lung and pleura; leukaemia and lymphoma; accidental causes. Among the economic sectors with a significant excess mortality, the following are well documented in the literature: mortality due to COPD in the coal and peat-bog sectors; due to leukaemia among farmers; due to sino-nasal tumours in wood-working and furniture production; due to cancer of the larynx, lung, and pleura in occupations where there was probable exposure to asbestos (fishing and maritime transport, non-metal mining, building industry, and naval, train and aircraft construction); due to silicosis in industries with potential exposure to crystalline silica; due to accidental causes in the building industry and farming. Other mortality excesses and deficits, especially those due to bladder and lympho-haemopoietic cancers, appear to be only partly consistent with those described by other authors. DISCUSSION: The feasibility of developing a surveillance system of occupational mortality based on the INPS source was found to be good, and, at least among males, for 75% of the deceased subjects historical information existed concerning the economic sectors registered in the INPS records. The results obtained would appear to indicate that the system is capable of highlighting risk excesses due to widespread exposure in the industries examined, regarding diseases for which there is a strong association with exposure. On the other hand, due to the inherent limits of the study's design (lack of a complete work history and of precise information on the jobs held) its use is not recommended in the surveillance of diseases with a low proportion attributable to a risk factor, or with wide exposure variability in a given sector among the various jobs.

Adult↗

PubMed2005

[Study of the relationship among work and demographic characteristics, sickness absence and occupational mobility].

BACKGROUND: The problem of sick absences from work is correlated to a series of organizational, social and psychological factors which interact with risk factors typical of the work performed, and thus determine how frequently absences occur. The correlation between morbidity and work is of interest in itself for studying the processes of occupational mobility. OBJECTIVES: To examine, using data from administrative sources, the association of sick absence with individual and workplace factors, as well as the relationship between illness and career mobility. METHODS: Employee sick absence data registered at INPS (National Institute of Social Insurance) in the period 1992-95 were studied using a sample of 124,686 subjects. RESULTS: The probability of being absent from work due to illness did not appear to be affected by sex or age. The sectors more at risk for sick absences were the service sector, business and commerce. Inequalities were noted in illness rates to the disadvantage of those who had received redundancy payments in the previous years. New hirings and upward mobility were associated with a lower occurrence of illness. A higher probability of illness was observed in those who had lost their jobs and in those who had changed from full-time to part-time work. CONCLUSIONS: It is likely that formal regulations and practices in use within INPS vary according to the different economic activities. Therefore this source allows investigation of illness only in activities with homogeneous regulatory aspects. The results confirm a link between unstable work situations and illness and between illness and career advancement.

Adult↗

PubMed2005

[Use of pension records for occupational health surveillance: example of record-linkage with hospital discharge records to study the association between work and the incidence of leukaemias, lung and bladder cancer, and miscarriage].

BACKGROUND: Epidemiologic surveillance of occupational health based on routinely collected data allows groups of workers to be studied, whose type of work (e.g. small enterprises, self-employed workers, artisans) makes it difficult to use a traditional cohort study design. OBJECTIVE: To evaluate the validity of a study design based on the record-linkage between hospital discharge records and INPS social security records (National Institute for Social Security), in order to investigate the association between past employment in an economic sector and occurrence of diseases with a low fraction attributable to occupation and a high frequency in the population, where it is too costly to perform retrospective interviews to gather data from each recruited subject. METHODS: A case-control study design was used in which hospital discharge records from 1995 in the Piedmont Region represented the source of subjects enrolled. Four series of cases were identified: males aged 40-75 years, with first hospital admission for leukaemia, lung or bladder cancer; and women aged 18-39 years, admitted for miscarriage. The controls were a random sample of patients admitted in the same year and matched by sex and age. The exposure variable was the prevalent economic sector in the occupational history of the subjects enrolled, as inferred from INPS social security records. RESULTS: No economic sector examined showed a significant excess of incidence of bladder cancer or leukaemia. There was a significant excess of lung cancer in subjects with longest employment in the building industry, in metal working, and in the "foundries, heat pressing, forging, and rolling mills" sector. A significant excess of miscarriages was present only in women working in commerce. DISCUSSION: The results demonstrated overall a low consistency compared with those obtained via other surveillance systems of occupational morbidity and mortality, as well as by means of analytical studies. The results appear more plausible for the sectors characterized by a low number of job tasks, or by a more homogenous exposure to risk factors among workers in different jobs. Among the limitations of this study the lack of a complete occupational history, the absence of information on potential confounders like smoking and alcohol consumption, and the probable non-differential misclassification of the longest held job need to be stressed

Abortion, Spontaneous↗