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Biomedical subjects

M P Amato

Publications and source records attributed to M P Amato.

At least 19 recordsLinked to original sources
PubMed2004

The prevalence of pain in multiple sclerosis: a multicenter cross-sectional study.

In a multicenter cross-sectional study, the authors assessed pain in patients with multiple sclerosis (MS) using a symptom-oriented approach. Out of 2,077 questionnaires, we used 1,672 for data analysis. Pain and frequencies included trigeminal neuralgia 2%, Lhermitte's sign 9%, dysesthetic pain 18.1%, back pain 16.4%, and painful tonic spasms 11%. Comparison between different groups showed significant differences for age, Expanded Disability Status Scale, disease duration, and disease course, but not for sex. This study underlines the relevance of pain in the clinical history of MS.

Adolescent↗
PubMed2004

A double blind, placebo-controlled, phase II, add-on study of cyclophosphamide (CTX) for 24 months in patients affected by multiple sclerosis on a background therapy with interferon-beta study denomination: CYCLIN.

The authors present and discuss a new protocol for active multiple sclerosis (MS) patients. A double blind randomized controlled multicenter study was planned to study the effects of a combination regimen therapy: cyclophosphamide plus beta interferon versus beta interferon alone on both relapsing-remitting and secondary MS patients with active disease. The primary endpoint of this study is the number of new gadolinium enhancing lesions at MRI evaluation. Secondary endpoints are new T2 lesions, new T1 lesions, T2 lesion load, T1 lesion load, cerebral atrophy, number of patients who were relapse-free, number of patients who improved, yearly relapses, quality of life, disability and cognitive impairment, frequency of neutralizing antibodies, safety of the combination therapy (cyclophosphamide + beta interferon). The study will enroll 225 patients in 25 Italian MS centers. Eligible for the study are patients with either relapsing-remitting or secondary MS according McDonald criteria on 6-24 months beta interferon treatment with active disease (new gadolinium enhancing lesion or who experienced a new relapse on beta interferon treatment). Clinical evaluation will be performed every 4 months, MRI yearly. Vital signs and eventual adverse events will be collected monthly. The study will last 36 months, 12 for the enrollment phase and 24 for the treatment phase. The study will start on April 2004.

Central Nervous System↗
PubMed2004

Neocortical volume decrease in relapsing-remitting MS patients with mild cognitive impairment.

OBJECTIVE: To assess neocortical changes and their relevance to cognitive impairment in early relapsing-remitting (RR) multiple sclerosis (MS). METHODS: Conventional MR was acquired in 41 patients with RR MS and 16 demographically matched normal control subjects (NCs). An automated analysis tool was used with conventional T1-weighted MRI to obtain measures of cortical brain volumes normalized for head size. Neuropsychological performance of MS patients was assessed using the Rao Brief Repeatable Battery. Relationship between volumetric MR measures and neuropsychological scores was assessed. RESULTS: Neuropsychological assessment allowed for the identification of 18 cognitively preserved (MS-cp) and 23 cognitively impaired (MS-ci) MS patients. The whole MS sample showed lower values of normalized cortical volumes (NCVs) than did the NC group (p = 0.01). Upon grouping of MS patients according to cognitive performance, NCV values were lower (p = 0.02) in MS-ci patients than in both MS-cp patients and NCs. Moreover, there were positive correlations 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 decreased in patients who scored lower on a greater number of tests (r = -0.58, p < 0.01) in the MS-ci group. None of the neuropsychological measures correlated to NCV values in the MS-cp patient group. CONCLUSIONS: Cortical atrophy was found only in cognitively impaired patients and was significantly correlated with a poorer performance on tests of verbal memory, attention/concentration, and verbal fluency. Gray matter pathology may contribute to the development of cognitive impairment in MS from the earliest stages of the disease.

Adult↗
PubMed2004

Altered cerebellar functional connectivity mediates potential adaptive plasticity in patients with multiple sclerosis.

BACKGROUND: The cerebellum is of potential interest for understanding adaptive responses in motor control in patients with multiple sclerosis because of the high intrinsic synaptic plasticity of this brain region. OBJECTIVE: To assess the relative roles of interactions between the neocortex and the cerebellum using measures of functional connectivity. METHODS: A role for altered neocortical-cerebellar functional connectivity in adaptive responses to injury from multiple sclerosis was tested using 1.5 T functional magnetic resonance imaging (fMRI) during figure writing with the dominant right hand in patients with predominantly early relapsing-remitting multiple sclerosis. RESULTS: Patients (n = 14) showed a more bihemispheric pattern of activation in motor cortex than healthy controls (n = 11). Correlations between task related signal changes in neocortical and cerebellar regions of interest were used as a measure of functional connectivity. Healthy controls showed strong functional connectivity between the left motor cortex and the right cerebellar dentate nucleus. Significant connectivity between the left primary motor cortex and the right dentate was not found in patients. However, patients had significant connectivity between the left premotor neocortex and the ipsilateral (left) cerebellar cortex (crus I), which was not found in healthy controls. CONCLUSIONS: Changes in apparent cerebellar-neocortical functional connectivity may mediate potentially adaptive changes in brain motor control in patients with multiple sclerosis. Similar changes in the cerebellum and premotor cortex have been reported in the healthy brain during motor learning, suggesting that common mechanisms may contribute to normal motor learning and motor recovery after injury from multiple sclerosis.

Adolescent↗
PubMed2003

Can the Expanded Disability Status Scale be assessed by telephone?

Information from patients who are unable to continue their visits to a study centre may be of major importance for the interpretation of results in multiple sclerosis (MS) clinical trials. To validate a questionnaire based on the Expanded Disability Status Scale (EDSS), patients in five different European centres were assessed independently by pairs of trained EDSS raters, first by telephone interview and a few days later by standardized neurological examination. Seventy women and 40 men with an average age of 43.7 years (range 19-74 years) were included in the study. Mean EDSS score at the last visit was 4.5 (0-9). EDSS assessment by telephone was highly correlated with the EDSS determined by physical examination (Pearson's correlation coefficient = 0.95). An intraclass correlation coefficient (ICC) of 94.8% was found for the total sample; 77.6% and 86%, respectively, for patients with EDSS < 4.5 (n = 46) and > 4.5 (n = 64). Kappa values for full agreement were 0.48; for variation by +0.5 steps and +1.0 steps, 0.79 and 0.90, respectively. Best agreement could be found in higher EDSS scores, where assessment by telephone interview might be needed most. The telephone questionnaire is a valid tool to assess EDSS score in cases where the patient is unable to continue visiting a study centre or in long-term follow-up of trial participants.

Adult↗
PubMed2003

Safety and tolerability of cyclophosphamide 'pulses' in multiple sclerosis: a prospective study in a clinical cohort.

To assess the safety and tolerability of cyclophosphamide (CTX) 'pulse' therapy in progressive or very active multiple sclerosis (MS), we reviewed our experience in a cohort of MS patients who have been treated and prospectively followed-up in our Department since 1997. One hundred and twelve patients received intravenous CTX in monthly 'pulses' for 12 months at the dosage of 700 mg/m2 of body surface, then bimonthly for another 12 months. We evaluated the frequency and the severity of side-effects, as well as overall tolerability by the patient perspective using a visual analogue scale (VAS). Side-effects resulted in the discontinuation of therapy in 20 (18%) cases. Serious side-effects were observed in 24 patients (21.4%), most commonly definitive amenorrhea (33.3% of fertile women), hypogammaglobulinemia (5.4%), and hemorrhagic cystitis (4.5%). Malignancies were diagnosed in four (3.6%) subjects, three of whom were previously treated with azathioprine (AZA). Finally, 81.8% of the patients judged the treatment regimen as very or relatively acceptable and tolerable. Our data point to a reasonable safety and tolerability of CTX 'pulse' therapy. Further trials are needed to definitively assess the efficacy of CTX as an alternative therapeutic option for progressive or very active MS.

Adult↗
PubMed2003

Interobserver agreement on Poser's and the new McDonald's diagnostic criteria for multiple sclerosis.

We assessed the interobserver agreement on the diagnosis of multiple sclerosis (MS) in a study sample consisting of 41 MS (15 relapsing remitting, two secondary progressive, five primary progressive and 19 presenting their first clinical attack) and three non-MS cases. Clinical and paraclinical information was recorded in standardized forms. Four neurologists were asked to make a diagnosis using Poser's and McDonald's criteria and to assess MRI scans according to the McDonald's guidelines. In terms of the kappa statistic (kappa), we found a moderate agreement on the overall diagnosis using both Poser's and McDonald's criteria (kappa, respectively 0.57 and 0.52). As for distinct diagnostic categories, we observed a moderate to substantial agreement for the three McDonald categories (range of kappa values 0.49-0.64) and a fair to substantial agreement for the nine Poser categories (range of kappa values 0.37-0.67). Taking into account clinical information, the agreement on dissemination over time was substantially higher (kappa = 0.69) than that found on dissemination over space (kappa = 0.46). In contrast, for MRI assessment, the agreement for spatial dissemination was substantial (kappa = 0.74) compared with the fair agreement (kappa = 0.25) yielded by dissemination over time. The new McDonald's criteria yield a good overall diagnostic reliability, and compare favourably with Poser's classification in terms of agreement on distinct diagnostic categories.

Adult↗
PubMed2003

Clinical management of cognitive impairment in multiple sclerosis: a review of current evidence.

Over the past decade, there has been considerable interest in assessing the importance and functional impact of cognitive impairment in multiple sclerosis (MS), its clinico-magnetic resonance imaging correlates, and possible approaches to clinical management. There is preliminary evidence that treatment with both disease-modifying and symptomatic agents may positively influence the cognitive outcome of the patient, but few studies have assessed the efficacy of cognitive rehabilitation programmes using an experimental design. To make further progress in the field of neuropsychological diagnosis, it is essential to validate sensitive, cost-effective and reliable screening instruments that can be used, in clinical settings, to identify patients appropriate for extensive neuropsychological assessment, and finalize tailor-made rehabilitation techniques for MS patients.

Cognition Disorders↗
PubMed2001

Cognitive dysfunction in early-onset multiple sclerosis: a reappraisal after 10 years.

OBJECTIVE: To reassess, in a cohort of patients with early-onset multiple sclerosis, the long-term evolution of cognitive deficits, their relationship to the disease's clinical progression, and their effects on daily life. DESIGN: Ten years after our baseline assessment, we again compared the cognitive performance of patients and control subjects on a neuropsychological test battery. Clinical and demographic correlates of cognitive impairment and their effects on everyday functioning were determined by multiple linear regression analysis. SETTING: The research clinic of a university department of neurology. PARTICIPANTS: Forty-five inpatients and outpatients with multiple sclerosis and 65 demographically matched healthy controls from the original sample. MAIN OUTCOME MEASURES: Mean scores of both groups on the neuropsychological test battery in initial and 2 follow-up evaluations (about 4 and 10 years, respectively); number of cognitively impaired subjects, defined by the number of subtests failed; regression coefficients measuring the relationship between clinical variables and cognitive outcome and between mental decline and everyday functioning assessed by the Environmental and the Incapacity Status Scales. RESULTS: Previously detected cognitive defects in verbal memory, abstract reasoning, and linguistic processes were confirmed on the third testing, at which time deficits in attention/short-term spatial memory also emerged. Only 20 of 37 patients who were cognitively unimpaired on initial testing remained so by the end of the follow-up, when the proportion of subjects who were cognitively impaired reached 56%. Degree of physical disability, progressive disease course, and increasing age predicted the extent of cognitive decline. Disability level and degree of cognitive impairment were independent predictors of a patient's handicap in the workplace and in social settings. CONCLUSIONS: In the course of a sufficiently long follow-up, cognitive dysfunction is likely to emerge and progress in a sizable proportion of patients. As multiple sclerosis advances, neurological and cognitive involvement tend to converge. Limitations in a patient's work and social activities are correlated with the extent of cognitive decline, independent of degree of physical disability.

Activities of Daily Living↗
PubMed2001

Quality of life in multiple sclerosis: the impact of depression, fatigue and disability.

This study deals with the assessment of quality of life and its main clinical and demographical determinants in a clinical series of 103 patients with multiple sclerosis (MS) (37 men; 66 women; mean age 44.89 years; mean disease duration 12.40 years; mean EDSS score 4.07). We used the MSQOL-54 inventory, a disease-specific instrument recently validated in an Italian population. Each patient underwent a complete clinical assessment, including that of disability status (Expanded Disability Status Scale), cognitive function (Mini Mental State Examination), depression (Hamilton Rating Scale for Depression) and fatigue (Fatigue Severity Scale). In terms of Pearson's correlations, there was a moderate inverse relationship between disability level and the MSQOL-54 physical composite score, and a moderate to strong inverse correlation between depression or fatigue severity and both the physical and mental composite scores. In a stepwise linear regression analysis, depression, fatigue and disability level were confirmed to be significant and independent predictors of quality of life. Quality of life instruments can help to provide a broader measure of the disease impact and to develop a care program tailored to the patient's needs.

Adult↗
PubMed2000

Association of apolipoprotein E polymorphism to clinical heterogeneity of multiple sclerosis.

In this study we investigated the distribution of apolipoprotein E (APO E) genotypes in sporadic multiple sclerosis (MS) cases and in normal controls. Later onset of chronic progressive MS was observed in patients carrying the epsilon2 allele, whereas APO E alleles were found at similar frequency in MS and in the control population. These findings indicate that clinical heterogeneity, but probably not susceptibility to the disease, is associated to APO E genotypes.

Adult↗
PubMed2000

A prospective study on the prognosis of multiple sclerosis.

Two hundred and twenty-four patients at their first diagnosis of multiple sclerosis (MS) were prospectively followed for a mean period of 9.78 years. We considered as endpoints the time to reach non-reversible disability levels corresponding to EDSS scores of 4.0 and 6.0, and the beginning of a secondary progressive phase in the relapsing-remitting subgroup of patients. An initially progressive course and higher basal EDSS scores proved to be the best predictors of unfavorable prognosis. A greater number of functional systems involved at onset as well as higher residual deficits in pyramidal, visual, sphincteric and cerebellar systems were other factors predictive of a poor outcome, whereas sensory system involvement turned out to be favorable. A longer first inter-attack interval was associated with a better prognosis. However, overall number of relapses in the first two years of the disease was of no prognostic value. The presence of oligoclonal banding in the cerebrospinal fluid and a cerebral MRI exam strongly suggestive or suggestive of MS in the early phases of the disease were associated with a higher probability of a worse outcome.

Adolescent↗
PubMed1999

A prospective study on the natural history of multiple sclerosis: clues to the conduct and interpretation of clinical trials.

The study's objectives were to assess the predictive significance of different sets of demographic, clinical and extraclinical variables in identifying multiple sclerosis patients with various risk levels of worsening during the follow-up, in order to provide clues to inclusion criteria and selection of primary clinical end-points in therapeutic trials. Two hundred and twenty-four patients at their first diagnosis of multiple sclerosis admitted to our Department between 1983 and 1990 were prospectively followed-up until the end of 1996. We considered as end-points time to reach non-reversible disability levels corresponding to EDSS scores of 4.0 and 6.0 and the beginning of a secondary progressive phase in the relapsing-remitting subgroup of patients. For the statistical treatment of our data we used the Kaplan-Meier survival curves and the Cox regression analysis. An initially progressive course and higher basal EDSS scores proved to be the best predictors of unfavorable prognosis; a greater number of functional systems involved at onset as well as higher residual deficits in pyramidal, visual, sphincteric and cerebellar systems were other factors predictive of a poor outcome, whereas sensory system involvement turned out to be favorable. In the relapsing-remitting subgroup, a longer first inter-attack interval was associated with a better prognosis; however, overall number of relapses in the first two years of the disease was of no prognostic value. The presence of oligoclonal banding in the cerebrospinal fluid and a cerebral MRI 'strongly suggestive' or 'suggestive' of MS in the early phases of the disease were associated with a higher probability of a worse outcome.

Adolescent↗
PubMed1999

Quantification of impairment in MS: discussion of the scales in use.

Accurate, efficient measurement of disease status has become a key issue in MS clinical practice and research. Despite some perceived problems, the Expanded Disability Status Scale (EDSS) remains the most widely used comprehensive measure of impairment. There is also a place for more restricted scales of impairment which focus on some aspects of neurological function in more detail than the EDSS e.g. measures of ambulation, arm function and cognitive function. Improvements in scales of impairment in the future is likely to result from the use of more quantitative tests of selected components of the neurological examination.

Disability Evaluation↗
PubMed1995

Cognitive impairment in early-onset multiple sclerosis. Pattern, predictors, and impact on everyday life in a 4-year follow-up.

OBJECTIVES: To assess the evolution of cognitive dysfunction in early-onset multiple sclerosis, to identify clinical predictors of mental decline, and to determine its impact on a patient's everyday life. DESIGN: The cognitive performance of 50 patients with multiple sclerosis on a neuropsychological battery was compared with that of 70 control subjects initially and again after a 4-year interval. Clinical predictors of cognitive impairment and its effect on daily life were analyzed by stepwise linear regression. SETTING: The research clinic of a university department of neurology. PARTICIPANTS: A consecutive sample of 50 inpatients and outpatients with multiple sclerosis (mean disease duration, 1.58 years) and 70 demographically matched healthy control subjects selected from the patients' relatives and friends. MAIN OUTCOME MEASURES: Mean psychometric test scores of both groups at the initial and follow-up testing. Regression coefficients measuring the relationship between clinical parameters and cognitive capacity and between mental decline and performance of common tasks measured by the Environmental and the Incapacity Status scales. RESULTS: Multiple sclerosis-related deficits in verbal memory and abstract reasoning on initial testing remained more or less stable on the retest, at which time linguistic disturbances on the Set and Token tests also emerged. A patient's initial disability level predicted decreased performance on only four of 13 cognitive variables, and disease duration did so on only two. Extent of intellectual decline on initial testing, initial disability level, and progressive course were independent determinants of handicap in a patient's work and social activities. CONCLUSIONS: Cognitive and neurological deficits appear not to develop in parallel. Yet cognitive dysfunction proves to be a predictor of handicap in everyday life, even in patients in the incipient phase of multiple sclerosis.

Adolescent↗
PubMed1994

Cross-national interrater agreement on the clinical diagnostic criteria for dementia. WHO-PRA Age-Associated Dementia Working Group, WHO-Program for Research on Aging, Health of Elderly Program.

We assessed the interobserver agreement on the clinical diagnosis of dementia syndrome and dementia subtypes as part of a cross-national project on the prevalence of dementia. Fourteen clinicians from the participating countries (Canada, Chile, Malta, Nigeria, Spain, and the United States) independently assessed the diagnosis of 51 patients whose clinical information was in standard records written in English. We used the DSM-III-R and ICD-10 criteria for dementia syndrome, the NINCDS-ADRDA criteria for Alzheimer's disease (AD), and the ICD-10 criteria for other dementing diseases, and measured interobserver agreement. We found comparable levels of agreement on the diagnosis of dementia using the DSM-III-R (kappa = 0.67) as well as the ICD-10 criteria (kappa = 0.69). Cognitive impairment without dementia was a major source of disagreement (kappa = 0.10). The kappa values were 0.58 for probable AD, 0.12 for possible AD, and rose to 0.72 when the two categories were merged. The interrater reproducibility of the diagnosis of vascular dementia was 0.66 in terms of kappa index; the diagnoses of other dementing disorders as a whole reached a kappa value of 0.40. This study suggests that clinicians from different cultures and medical traditions can use the DSM-III-R and the ICD-10 criteria for dementia effectively and thus reliably identify dementia cases in cross-national research. The interrater agreement on the diagnosis of dementia might be improved if clear-cut guidelines in the definition of cognitive impairment are provided. To improve the reliability of AD diagnosis in epidemiologic studies, we suggest that the NINCDS-ADRDA "probable" and "possible" categories be merged.

Aged↗