Biomedical subjects

Valentina Zipoli

Publications and source records attributed to Valentina Zipoli.

10 recordsLinked to original sources

PubMed2007

Early prediction of the long term evolution of multiple sclerosis: the Bayesian Risk Estimate for Multiple Sclerosis (BREMS) score.

AIM: To propose a simple tool for early prediction of unfavourable long term evolution of multiple sclerosis (MS). METHODS: A Bayesian model allowed us to calculate, within the first year of disease and for each patient, the Bayesian Risk Estimate for MS (BREMS) score that represents the risk of reaching secondary progression (SP). RESULTS: The median BREMS scores were higher in 158 patients who reached SP within 10 years compared with 1087 progression free patients (0.69 vs 0.30; p<0.0001). The BREMS value was related to SP risk in the whole cohort (p<0.0001) and in the subgroup of 535 patients who had never been treated with immune therapies, thus reasonably representing the natural history of the disease (p<0.000001). CONCLUSIONS: The BREMS score may be useful both to identify patients who are candidates for early or for more aggressive therapies and to improve the design and analysis of clinical therapeutic trials and of observational studies.

Adult↗

PubMed2006

Brain damage as detected by magnetization transfer imaging is less pronounced in benign than in early relapsing multiple sclerosis.

The trend to start disease-modifying therapy early in the course of multiple sclerosis makes it important to establish whether the benign form is a real entity. In previous studies, measures of magnetization transfer (MT) ratio (MTr) have been shown to provide good estimates of the amount of tissue damage occurring in multiple sclerosis brains. Thus, with the hypothesis that if benign multiple sclerosis patients were really benign, sensitive measures of subtle tissue damage would be less pronounced in these patients than in very early relapsing-remitting (RR) multiple sclerosis patients. We carried out conventional MRI and MT imaging in 50 patients with benign multiple sclerosis [defined as having Kurtzke Expanded Disability Status Score (EDSS) <3 and disease duration >15 years] and in 50 early RR patients selected to have similar disability (EDSS <3) and short disease duration (<3 years). Data were compared with those of 32 demographically-matched normal controls. We used a fully automated procedure to measure lesional-MTr, perilesional-MTr, normal-appearing white matter (NAWM) MTr and cortical-MTr. We found that, after correction for common effects of age, lesional-MTr and perilesional-MTr of benign patients were significantly (P < 0.0001) lower than WM of normal controls, but significantly (P < 0.0001) higher than corresponding tissues of RR patients. In NAWM and cortex, MTr values of benign patients were similar to those of normal controls (P > 0.5) and significantly higher than those of the RR patients (P < 0.0001 and P < 0.01, respectively). Similar differences in MTr measures between benign and RR patients were found when patient groups were selected to have no disability (EDSS < or = 2) and, for benign multiple sclerosis, very long disease duration (>20 years) or when both groups were matched for high lesion load (T2-weighted lesion volume >10 cm3). We conclude that lesional and non-lesional MTr values can be significantly less pronounced in benign multiple sclerosis than in a cohort of RR patients at their earliest disease stages, suggesting that brain tissue damage is milder in benign multiple sclerosis than in early RR disease. This can be due to an extraordinary beneficial response to demyelination of benign patients and may represent the evidence that benign multiple sclerosis truly exists and might be differentiated from other forms of this illness.

Adult↗

PubMed2006

Are there protective treatments for cognitive decline in MS?

Despite its frequency and high functional impact, very little is known about effective strategies for managing cognitive impairment in multiple sclerosis (MS). Disease-modifying drugs, such as beta-interferons and glatiramer acetate, may prevent or reduce the progression of cognitive dysfunction by containing the development of new cerebral lesions. To date, clinical trials have provided inconsistent results, with neuropsychological effects documented only in one trial. Moreover, pilot studies have tested symptomatic therapies for fatigue, a frequent symptom in MS, which may share a common physiopathological substrate with cognitive dysfunction. Small trials with amantadine, pemoline, 4-aminopyridine and 3-4 aminopyridine have provided mainly negative results. Acetylcholinesterase inhibitors (AChEI) used to treat Alzheimer's disease (AD)-such as donepezil, rivastigmine, and galantamine-have recently been tested in other cognitive disorders, including MS. The majority of pilot trials with AchEI in MS have provided promising results, and the donepezil study recently published by Krupp et al. represents a major development in this field. As for non-pharmacological interventions based on cognitive rehabilitation, few studies have used an experimental approach and, in general, results have been disappointingly negative. Further research is clearly needed in this area.

Cholinesterase Inhibitors↗

PubMed2006

Multiple sclerosis-related cognitive changes: a review of cross-sectional and longitudinal studies.

Prevalence estimates of cognitive impairment in multiple sclerosis (MS) range from 40% to 65%, depending on the research setting. Cognitive dysfunction virtually encompasses all the disease stages and types of clinical course, although it is generally less frequent in relapsing-remitting (RR) patients compared with secondary progressive (SP) patients, and tends to be less frequent in primary progressive (PP) patients. Moreover, it causes role limitations in work and social life, independently of the degree of physical disability. Relatively little is known about the evolution of cognitive impairment in MS, particularly starting from the early stages of the disease. Controlled studies, however, have clearly shown that cognitive deterioration tends to progress over time. Among clinical predictors, incipient cognitive decline seems to be the major risk factor for further deterioration in the short-term. In the long-term, the likelihood increases that also patients with initial cognitive preservation may deteriorate. As for magnetic resonance imaging (MRI), there are consistent, albeit moderate, correlations between the progression of cognitive impairment and increasing brain lesion load and brain atrophy. The aim of this paper is to provide a review of existing cross-sectional and longitudinal studies on cognitive deterioration in MS.

Cognition Disorders↗

PubMed2006

Neocortical volume decrease in relapsing-remitting multiple sclerosis with mild cognitive impairment.

The aim of the study was to assess neocortical changes and their relevance to cognitive impairment in early relapsing-remitting multiple sclerosis (RRMS). Conventional magnetic resonance was acquired in 41 RRMS patients and 16 demographically matched normal controls (NC). An automated analysis tool was used to obtain measures of cortical brain volumes normalized for head size. Neuropsychological performance of MS patients was assessed through the Rao's Brief Repeatable Battery. We identified 18 cognitively preserved (MS-cp) and 23 cognitively impaired (MS-ci) MS patients. Values of normalized cortical volumes (NCV) in the whole MS sample were lower than those in the NC group (p=0.01). MS-ci patients showed NCV values lower (p=0.02) than did both MS-cp patients and NC. Moreover, we found a positive correlation between NCV values and measures of verbal memory (r=0.51, p=0.02), verbal fluency (r=0.51, p=0.01) and attention/concentration (r=0.65, p<0.001) in MS-ci patients. Furthermore, NCV values were significantly decreased in patients who scored lower on a greater number of tests (r=-0.58, p<0.01) in the MS-ci group. Only MS-ci patients had cortical atrophy significantly correlated with a poorer neuropsychological performance. Grey matter pathology may contribute to the development of cognitive impairment in MS from the earliest stages of the disease.

Adult↗

PubMed2006

Benign multiple sclerosis: cognitive, psychological and social aspects in a clinical cohort.

OBJECTIVES: A study of cognitive, psychological and social aspects in benign multiple sclerosis (MS). Methods One hundred and sixty three patients with benign MS (defined as disease duration > or = 15 years and Expanded Disability Status Scale (EDSS) score < or = 3.0 ) underwent neuropsychological testing on the Rao's Brief Repeatable Battery (BRB) and the Stroop test, evaluation of depression on the Montgomery and Asberg Depression Rating Scale (MADRS), of fatigue on the Fatigue Severity Scale (FSS) and of handicap on the Environmental Status Scale (ESS). Patients' cognitive performance was compared with that of 111 demographically matched healthy controls. Cognitive impairment was defined as the failure in at least 3 tests, using the fifth percentile of controls' performance as the cut-off point. Clinical correlates of cognitive impairment were determined by multiple logistic regression analysis. RESULTS: Cognitive assessment led to the identification of 74 subjects (45%) with cognitive impairment. Significant fatigue was found in 80 subjects (49%) and depression in 88 patients (54%). In comparison with cognitively preserved subjects, cognitively impaired patients exhibited higher handicap scores on the ESS (p = 0.005). In the regression analysis, only EDSS scores were significantly associated with cognitive impairment (OR 1.8, 95%CI 1.2-2.6). CONCLUSION: Current definitions of benign MS may overestimate this entity, since they are mainly weighted for the patients' motor abilities and fail to capture relevant disease-related cognitive, psychological and social problems.

Adult↗

PubMed2006

Absence of cerebrospinal fluid oligoclonal bands is associated with delayed disability progression in relapsing-remitting MS patients treated with interferon-beta.

To assess the role of CSF oligoclonal bands (OB) in determining the clinical outcome in patients with relapsing-remitting multiple sclerosis (RRMS) treated with IFN-beta, we carried out a retrospective, multicentre, observational study recruiting 209 RRMS patients from six MS centres from northern, central and southern areas of Italy under treatment with IFN-beta-1a i.m., IFN-beta-1a s.c. and IFN-beta-1b s.c. Twenty-two of 209 patients (10.6%) showed no OB in CSF. The patients without had, at disease onset, significantly higher frequency of visual disturbances (p=0.02) and less sensory involvement (p=0.04) than those with OB. A statistical trend (p=0.056) towards a longer time to reach sustained disability progression during treatment was found in patients without compared to those with OB. Thirty-six of 187 (19%) patients with OB worsened by at least 1 EDSS point compared to none of 22 (0%) OB-negative patients (p=0.017). The delaying of disability progression in OB-negative patients during treatment was significantly dependent only on the number of baseline MRI T2-weighted lesions (p=0.012) that was found to be significantly lower in OB-negative than in OB-positive patients (p=0.04). The absence of OB and low number of baseline T2-weighted lesions in this cohort of MS patients are favourable prognostic factors influencing the clinical response to IFN-beta treatment in RRMS patients.

Adult↗

PubMed2005

The glycopeptide CSF114(Glc) detects serum antibodies in multiple sclerosis.

Synthetic glycopeptides have the potential to detect antibodies in multiple sclerosis (MS). In the present study, we analyzed the antibodies (IgM class, IgG class and IgG subclasses) to the synthetic glycopeptide CSF114(Glc) in the serum of 186 MS patients, 166 blood donors (BDs), 25 patients affected by meningitis/encephalitis, 41 affected by systemic lupus erythematosus (SLE) and 49 affected by rheumatoid arthritis (RA). The IgM antibody level to CSF114(Glc) was significantly increased in MS patients versus BDs (p<0.001) or versus other autoimmune diseases (SLE or RA, p<0.001). The IgG response was restricted to the subclass IgG2. IgM antibodies to CSF114(Glc) were found in 30% of relapsing/remitting MS patients and, at lower levels, in subjects affected by meningitis/encephalitis. The study of antibodies to CSF114(Glc) is a new, potential immunological marker of MS.

Adolescent↗

PubMed2004

Influence of apolipoprotein E epsilon4 genotype on brain tissue integrity in relapsing-remitting multiple sclerosis.

BACKGROUND: Recent clinical and imaging studies have raised the hypothesis that patients with multiple sclerosis (MS) and the apolipoprotein E (ApoE) epsilon4 allele may have a more severe disease course than those without the ApoE epsilon4 allele. This seems to be related to more extensive tissue destruction and less efficient neuronal maintenance and repair in ApoE epsilon4 carriers. OBJECTIVE: To evaluate the influence of different ApoE genotypes on brain tissue integrity in patients with relapsing-remitting MS (RRMS). DESIGN: We determined the ApoE genotype in 76 RRMS patients. Conventional T1-, T2-, and proton density-weighted magnetic resonance (MR) images were obtained for each patient and in a group of demographically matched healthy control subjects. On conventional T1-weighted MR images, an automated analysis tool was used to obtain total brain volumes normalized for head size (NBVs). Total brain lesion load was estimated on proton density- and T2-weighted MR images. RESULTS: From the whole group of RRMS patients, we identified 18 with and 58 without the epsilon4 allele. Both patient groups were not significantly different in age, age of disease onset, clinical disability, and disease duration. Carriers of the epsilon4 allele showed significantly (P =.01) lower NBVs than controls and non-epsilon4 allele carriers. When a similar analysis was performed on only those patients with both very short disease duration and absence of clinical disability, NBV values were still significantly lower in RRMS patients with the epsilon4 allele than in those without it (P =.02) and in controls (P =.007). In contrast, RRMS patients with different ApoE genotypes did not show significant differences in values of total brain T2-weighted lesion volumes. CONCLUSIONS: The presence of significant NBV decreases only in the group of RRMS patients with the ApoE epsilon4 genotype provides new evidence that links ApoE epsilon4-related impaired mechanisms of cell repair and severe tissue destruction in MS. Results of the present study suggest that this negative influence of the ApoE epsilon4 genotype might be active from the earliest disease stages.

Adult↗

PubMed2003

Changes in neuropsychological test performance over the workday in multiple sclerosis.

Fatigue, a common symptom of multiple sclerosis (MS), is associated with impairment in performing daily activities, poor quality of life and premature retirement from the workforce. There is little doubt that patients with MS can exhibit marked weakness and other objective signs of physical fatigue, but whether cognitive performance by patients declines more rapidly than that by controls as a function of time engaged in mental activity remains controversial. Krupp and Elkins (2000) reported more rapid deterioration of performance by MS patients on two of five cognitive measures when subjects performed 3 hr of continuously effortful tasks between baseline and posttest. Others, using shorter and less taxing interpolated tasks found similar changes in performance over time for patients and controls. In the present study participants completed a timed walk, fatigue ratings and four cognitive tests that emphasized processing novel information before they went to work and again after completing a normal workday. Patients with MS walked somewhat more slowly and performed more poorly on two of the cognitive tests, but they did not show more decline from baseline to posttest on any of these objective measures of cognitive fatigue. By contrast, subjective ratings of fatigue showed a greater increase over the day for patients than for controls. These results confirm other reports that patients' subjective ratings of their fatigue are not valid indicators of their actual performance on cognitive tests. Furthermore, laboratory studies that report "objective" cognitive fatigue in MS may utilize conditions that model the cognitive fatigue associated with the jobs patients actually perform rather poorly.

Adult↗