Acute promyelocytic leukemia following mitoxantrone as single agent for the treatment of multiple sclerosis.
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Adult↗
Biomedical subjects
B Colombo
Publications and source records attributed to B Colombo.
Magnetization transfer ratios in multiple sclerosis lesions enhancing after different doses of gadolinium.
We performed serial monthly magnetization transfer (MT) imaging to evaluate whether MS lesions that enhance only after the injection of a triple dose (TD) of gadolinium-DTPA (Gd) have different pathologic characteristics and evolution than those that enhance after the injection of a standard dose (SD). Every 4 weeks for 3 months and in two separate sessions, we obtained T1-weighted scans from 10 patients with relapsing-remitting MS, 5 minutes after SD (0.1 mmol/kg) or TD (0.3 mmol/kg) Gd injection. During each of the first monthly sessions, we obtained MT images and dual-echo scans before Gd injection. We measured the MT ratio (MTR) of newly enhancing lesions on co-registered quantitative MTR images. During the 3-month follow-up, 81 newly enhancing lesions were seen on SD scans. An additional 46 lesions enhanced only on TD scans. The mean (+/- standard deviation) MTR values were 31.4% +/- 8.4% for lesions enhancing after SD and 38.2% +/- 6.0% for lesions enhancing only after TD injection (p < 0.0001). The mean MTR values of lesions seen with both SD (p < 0.00001) and TD (p = 0.002) increased significantly during the follow-up. At each time point during the follow-up, the MTR values of TD lesions were significantly higher than the SD lesions. These results indicate that the enhancing lesion population in MS is heterogeneous and that the tissue damage occurring within lesions enhancing only after TD injection is less severe than in lesions enhancing after the injection of an SD.
Adult↗
Benign versus secondary-progressive multiple sclerosis: the potential role of proton MR spectroscopy in defining the nature of disability.
PURPOSE: We determined the clinical utility of proton MR spectroscopy in defining the extent of disability in benign versus secondary-progressive multiple sclerosis (MS). METHODS: Thirty patients with clinically definite MS, including 16 patients with benign MS and 14 with secondary-progressive MS, and a group of 13 healthy volunteers were studied with combined stimulated-echo acquisition mode proton MR spectroscopy and MR imaging (all patients received contrast material). RESULTS: Acute enhancing lesions of benign and secondary-progressive MS were characterized by a reduction in N-acetylaspartate (NAA)/choline and NAA/creatine and an increase in inositol compounds/creatine as compared with normal white matter. Such variations were also detected in chronic unenhancing lesions in patients with secondary-progressive MS, although they were not found in chronic unenhancing lesions in patients with benign MS. Chronic lesions of the two forms of the disease have significative differences in NAA and inositol signals. CONCLUSION: Proton MR spectroscopy is able to show metabolic changes occurring in the white matter of patients with MS. Such changes differ according to the phase (acute versus chronic) and the clinical form (benign versus secondary-progressive) of the disease.
Adult↗
Increased spatial resolution using a three-dimensional T1-weighted gradient-echo MR sequence results in greater hypointense lesion volumes in multiple sclerosis.
PURPOSE: Our goal was to evaluate whether improved spatial resolution of MR images results in the detection of higher volumes of hypointense lesions in patients with multiple sclerosis (MS). METHODS: A magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) sequence with subsequent reconstruction of axial sections with 5-, 3-, and 1-mm thickness and a dual-echo sequence were obtained in 16 patients with relapsing-remitting or secondary-progressive MS. The volumes of MR imaging abnormalities present on each of these studies were measured using a semiautomated segmentation technique based on local thresholding. The hypointense lesion volumes seen on the three reconstructed MP-RAGE sets of images were compared using the Friedman test and correlated with the hyperintense lesion volume on proton density-weighted images and with scores on the Expanded Disability Status Scale using Spearman's rank correlation coefficient. RESULTS: The median volume of hypointense lesions increased from 1.2 mL (range, 0 to 14.9 mL) on the 5-mm-thick MP-RAGE images to 1.7 mL (range, 0 to 15.8 mL) on the 3-mm-thick images, and to 1.9 mL (range, 0 to 16.2 mL) on the 1-mm-thick images. The hypointense lesion volumes measured on the three MP-RAGE images correlated significantly with the degree of disability, whereas this correlation was not significant with the T2-weighted lesion load. CONCLUSION: Our findings indicate that a significant increase in the volume of potentially disabling MS lesions is observed when obtaining MR images with thin sections.
Adult↗
A magnetization transfer study of white matter in siblings of multiple sclerosis patients.
In this study, we evaluated magnetization transfer ratio values in the brain white matter of siblings of multiple sclerosis (MS) patients and compared them to those obtained in sex- and age-matched normal controls. No statistically significant difference was found between the two groups for all the white matter areas studied (frontal and occipital lobes, centrum semiovale, periventricular white matter, internal capsule, genu and splenium of the corpus callosum).
Adult↗
Significance of the DNA synthesis in hypertrophic cardiomyopathies.
DNA content and proliferating cell nuclear antigen (PCNA) expression were investigated in normal hearts, in hypertrophic from hemodynamic overload hearts and in hypertrophic cardiomyopathy (HCM). The aim of this study was mainly to determine whether the hyperdiploid myocardial cells in all cases are in dynamic or static phase. The percentage of PCNA positive cells only in the HCM group was significantly higher (mean value = 25.4%) than the percentage of hyperdiploid cells (mean value = 9.3%). Therefore, the DNA replication occurs through a different process from that of normal cell cycle which lead to an increase in ploidy and eventually mitosis. These data should be interpreted not only as the result of a periodic amitotic DNA renewal and not even as the result of an increased apoptosis, but especially as a repair process of the DNA molecules affected by a various types of damages in HCMs.
Adult↗
Intra-observer reproducibility in measuring new putative MR markers of demyelination and axonal loss in multiple sclerosis: a comparison with conventional T2-weighted images.
New magnetic resonance (MR) measures considered to be putative workers of demyelination and axonal loss were found to be more closely related to clinical disability than T2-weighted MR imaging (MRI) findings in patients with multiple sclerosis (MS). In this study, we evaluated the reproducibility of such measurements in order to assess their reliability for longitudinal studies in MS. The intra-observer coefficients of variation for repeated measurements did not significantly differ among the MR techniques studied [2.6% for T2-weighted MR, 4.38% for unenhanced T1-weighted MRI, 3.65% for magnetisation transfer imaging (MTI) and 2.28% for spinal cord cross-sectional area at C5]. Our findings suggest that non-conventional MR techniques may be reliable outcome measures for clinical trials in MS.
Adult↗
Headache in a population-based elderly cohort. An ancillary study to the Italian Longitudinal Study of Aging (ILSA).
The aims of this ancillary study to the Italian Longitudinal Study of Aging were: (1) to provide reliable prevalence data on headache in an elderly population, (2) to classify the subtypes of headache according to International Headache Society criteria, and (3) to identify possible risk factors and associated pathologies in the elderly. A total of 312 subjects were examined, 148 women and 164 men, with a mean age of 73 years (SD 5.5). For 236 subjects (75.7%), 141 men (85.9%) and 95 women (64.2%), headache had never been a problem; 57 subjects (18.3%), 21 men (12.8%) and 36 women (24.3%), reported troublesome headache only in the past. Nineteen subjects (6%), 6 men (3.6%) and 13 women (8.8%), reported current headache: in this group tension-type headache was the most prevalent, accounting for 2.6%; secondary headaches ranked second, accounting for 2.2%; and only 1% had current migraine. Our data indicate female sex and younger age as risk factors for headache, and associate migraine and secondary headaches with hypertension, tension-type headaches and secondary headaches with diabetes, and tension-type headaches with myocardial ischemia.
Age Factors↗
A longitudinal magnetic resonance imaging study of the cervical cord in multiple sclerosis.
This study was performed to evaluate the correlation between changes of cross-sectional cord area and disability in multiple sclerosis. Axial magnetic resonance images at the C-5 spinal level were obtained at entry and 12 months later for 29 patients with clinically definite multiple sclerosis. The degree of disability was inversely correlated at entry and follow-up with the cross-sectional area and the transverse diameter of the spinal cord. In addition, changes in disability correlated inversely with changes in cross-sectional area (r = -0.4, p = 0.04). These findings suggest that cross-sectional cord area at C-5 might be a useful marker of disease evolution.
Adult↗
Serial contrast-enhanced MR in patients with multiple sclerosis and varying levels of disability.
PURPOSE: To compare the rates of enhancement and changes in lesion burden in patients with multiple sclerosis (MS) and varying levels of disability. METHODS: Monthly enhanced MR images of the brain were obtained for 6 months from seven patients with mildly disabling relapsing-remitting MS and from seven patients with secondary progressive MS and severe disability. At entry and 1 year later, two unenhanced T2-weighted images of the brain were also obtained. RESULTS: Despite the fact that both groups had clinically active disease and had similar increases in unenhanced MR lesion load, the total number of enhancing lesions was 239 in patients with relapsing-remitting MS (42 on the baseline images, 151 new and 46 persistent during follow-up) (average number of lesions per patient per year was 68) and 21 in those with secondary progressive MS (five on the baseline images, 13 new, and three persistent during follow-up) (average number of lesions per patients per year was seven). CONCLUSION: Our data indicate that the rate of enhancement significantly decreases in the more advanced phases of MS. This is important when planning clinical trials, and suggests that mechanisms underlying lesion formation might be dissimilar in different MS patient groups.
Activities of Daily Living↗
A spinal cord MRI study of benign and secondary progressive multiple sclerosis.
This study was performed to achieve a better definition of the nature of the disability in multiple sclerosis (MS). Axial spinal cord magnetic resonance imaging (MRI) at C5 was obtained in 15 patients with benign MS, 17 patients with secondary progressive MS and 10 healthy controls. Patients with secondary progressive MS had smaller spinal cord cross-sectional area (P = 0.01) and transverse diameter (P = 0.006) than patients with benign MS. The degree of disability was inversely correlated with both the cross-sectional area (r = -0.6, P = 0.0018) and transverse diameter (r = -0.5, P = 0.0032) of the cord. Spinal cord atrophy was found in 7 (41%) patients with secondary progressive MS and in 2 (13%) with benign MS. These findings suggest that destructive pathology within MS lesions might play a relevant role in the development of disability in MS.
Adult↗
Brain and spinal cord MR in benign multiple sclerosis: a follow-up study.
We performed a clinical and magnetic resonance (MR) longitudinal study in 19 patients with benign multiple sclerosis (MS) to achieve a better definition of the nature of disability in MS. Patients with higher lesion volumes on conventional T2-weighted images at entry were those with more frequent relapses (p = 0.0004) and more new MR lesions (p = 0.003) during the follow up. However, 1/3 of these new lesions were located periventricularly and about 2/3 were small or intermediate in size. Two of the 11 patients (18%) with higher lesion volumes at entry developed progressive neurological deficits: in these two patients the new lesions seen on conventional T2 images had lower magnetization transfer ratios (p = 0.005) than those present in patients who remained clinically stable and a marked increase in hypointense lesion volumes on T1-weighted images was also found. Spinal cord cross-sectional area at C5 and MTR values for the seemingly normal white matter were similar to those found in normal controls. This study suggests that patients with benign MS have two different patterns of disease evolution, one characterized by very low clinical and MR activities, the other in which the lack of disabling symptomatology might be related to factors like site, size and nature of lesions. It also indicates that in patients with benign MS and high MR lesion loads the risk of developing a secondary progressive form of the disease is still present even after many years after onset.
Adult↗
Correlation between brain MRI lesion volume and disability in patients with multiple sclerosis.
In this study we evaluated the relationships between clinical variables and lesion volumes measured from magnetic resonance imaging (MRI) scans in a large cohort of multiple sclerosis (MS) patients. One hundred and thirty patients with MS entered the study: 36 patients had relapsing-remitting (RR), 39 benign (B), 42 secondary progressive (SP) and 13 primary progressive (PP) courses. There was a significant correlation (r = 0.3; p = 0.0006) between the total lesion load and the EDSS score when the whole cohort of patients was considered. This correlation increased (r = 0.5) when only patients with RRMS and SPMS were considered. Our data indicate that a correlation between disability and MRI lesion volume in MS exists, but its strength is moderate.
Adult↗
Triple dose of gadolinium-DTPA and delayed MRI in patients with benign multiple sclerosis.
OBJECTIVES: To evaluate whether a triple dose of gadolinium-DTPA (Gd-DTPA) or delayed MRI increase the number, size, and conspicuousness of enhancing lesions in patients with benign multiple sclerosis. METHODS: T1 weighted brain MRI was carried out on 20 patients with benign multiple sclerosis (expanded disability status scale < 3 with a disease duration > 10 years) in two sessions. In the first session, one scan was obtained before and two scans five to seven minutes and 20-30 minutes after the injection of 0.1 mmol/kg Gd-DTPA (standard dose). In the second session, six to 24 hours later, the same procedure was repeated with 0.3 mmol/kg Gd-DTPA (triple dose). RESULTS: Nine enhancing lesions were found in seven patients (35%) using the standard dose of Gd-DTPA. The numbers of enhancing lesions increased to 13 (P = 0.03) and the number of patients with such lesions to eight (40%) on the delayed standard dose scans. On the early triple dose scans, we found 19 enhancing lesions in 10 patients (50%). The number of enhancing lesions was significantly higher (P = 0.01) than that obtained with the early standard dose. The number of enhancing lesions was 18 and the number of "active" patients 11 (55%) on the delayed triple dose scans. The enhancing areas increased progressively from the early standard dose scans to the delayed triple dose scans. The contrast ratios of the lesions detected in early standard dose scans was lower than those of lesions present in the early (P = 0.01) and delayed (P = 0.04) triple dose scans. CONCLUSIONS: More enhancing lesions were detected in patients with benign multiple sclerosis with both delay of MRI and the use of triple dose of Gd-DTPA suggesting that the amount of inflammation in the lesions of such patients is mild and heterogeneous.
Gadolinium DTPA↗
Interferon-gamma activated calcium influx in peripheral blood lymphocytes from patients with primary and secondary progressive multiple sclerosis.
Interferon-gamma (IFN-gamma) contributes to the early events leading to T cell activation in relapsing-remitting (RR) multiple sclerosis (MS) by activating a transplasmalemma calcium influx, the detection of which is closely associated with clinical and MRI evidence of disease activity. The appearance of this influx represents one of the earliest peripheral events in the pathogenesis of RRMS. It is still questioned whether the same immune mediated mechanisms also operate in primary progressive (PP)MS. Fluorimetric evidence of the IFN-gamma activated calcium influx was sought in 16 patients with PPMS and 39 patients with secondary progressive (SP)MS. To compare peripheral versus CNS evidence of immune activation 11 of the patients with PPMS and 27 of the patients with SPMS underwent gadolinium enhanced brain MRI. The IFN-gamma activated influx was detected in peripheral blood lymphocytes from eight of 16 (50%) patients with PPMS, and 20 of 39 (51%) patients with SPMS, a frequency similar to that previously reported in patients with RRMS during phases of disease stability. Gadolinium enhancing brain MRI lesions were found in only one of 11 (9%) patients with PPMS and 12 of 27 (41%) with SPMS. Our study shows that peripheral blood lymphocytes from patients with PPMS and patients with SPMS express with the same frequency as patients with RRMS, an IFN-gamma dependent intracellular process leading to T cell activation able to trigger disease activity.
Adult↗
Comparison of triple dose versus standard dose gadolinium-DTPA for detection of MRI enhancing lesions in patients with MS.
We studied whether a triple dose of gadolinium-DTPA alone or in combination with delayed scanning increases the sensitivity of brain MRI for detecting enhancing lesions in patients with MS. We obtained T1-weighted brain MRI scans in two sessions for 22 patients with clinically definite MS. In the first session, we obtained one scan 5 to 7 minutes after the injection of 0.1 mmol/kg gadolinium-DTPA (standard dose). In the second session, 6 to 24 hours later, we obtained one scan before the two scans 5 to 7 minutes (for all patients) and one hour (for 11 patients) after the injection of 0.3 mmol/kg gadolinium-DTPA (triple dose). We detected 83 enhancing lesions in 14 patients when the standard dose of gadolinium-DTPA was used. The numbers of enhancing lesions increased to 138 (average increase 66%; p = 0.001) and the numbers of patients with such lesions to 18 (increase 28%) when we used the triple dose of gadolinium-DTPA. In addition, the total area per patient occupied by such lesions was greater (p < 0.0001) and lesion signal intensity higher (p = 0.0001) on the triple-dose scans than the standard-dose scans. There was an increase in the number of large enhancing lesions (p = 0.03) in the scans obtained 1 hour after the injection of the triple dose of gadolinium-DTPA. These data indicate that in patients with MS, a triple dose of gadolinium-DTPA can reveal many more enhancing lesions, which also appear larger. This suggests that the pathologic nature of "active" lesions in MS is heterogeneous, which might have impact on planning clinical trials.
Contrast Media↗
Acute myelopathy of unknown aetiology: a clinical, neurophysiological and MRI study of short- and long-term prognostic factors.
Brain and spinal cord magnetic resonance imaging (MRI), multimodal evoked potentials (EPs) and cerebrospinal fluid (CSF) analysis were performed in 27 patients with acute myelopathy of unknown aetiology (AMUA), to detect the diagnostic and prognostic values of paraclinical tests at presentation. Spinal cord MRI was abnormal in 56% and brain MRI in 33% of the patients. Visual EPs were abnormal in 7%, median somatosensory EPs in 17%, tibial somatosensory EPs in 56% and motor EPs in 35% of the cases examined. Brain-stem acoustic EPs were normal in all the patients. CSF oligoclonal bands (OBs) were detected in 30% of cases. The patients were divided into subgroups according to the short-term clinical outcome (complete, partial or absent recovery). There were no significant differences among the three groups as regards MRI findings. Patients with complete recovery showed a significantly lower frequency of tibial somatosensory EP and motor EP abnormalities. According to the paraclinical findings at onset and on the basis of a long-term clinical follow-up (mean duration 24 months), 6 patients were diagnosed as having clinically definite multiple sclerosis, while 21 did not develop further neurological disturbances. Only the presence of CSF OBs was significantly more frequent in patients with definite multiple sclerosis. Our study indicates that EPs exploring spinal cord function are more powerful than spinal MRI for predicting the short-term outcome of AMUA, while the combined use of brain MRI and CSF OBs has the highest negative predictive value for the subsequent development of clinically definite multiple sclerosis.
Acute Disease↗
Comparison of triple dose versus standard dose gadolinium-DTPA for detection of MRI enhancing lesions in patients with primary progressive multiple sclerosis.
This study was performed to evaluate whether a triple dose of gadolinium-DTPA (Gd-DTPA) increases the sensitivity of brain MRI for detecting enhancing lesions in patients with primary progressive multiple sclerosis (PPMS). T1 weighted brain MRI was obtained for 10 patients with PPMS in two sessions. In the first session, one scan was obtained five to seven minutes after the injection of 0.1 mmol/kg Gd-DTPA (standard dose). In the second session, six to 24 hours later, one scan before and two scans five to seven minutes and one hour after the injection of 0.3 mmol/kg Gd-DTPA (triple dose) were obtained. Four enhancing lesions were detected in two patients when the standard dose of Gd-DTPA was used. The numbers of enhancing lesions increased to 13 and the numbers of patients with such lesions to five when the triple dose of Gd-DTPA was used and to 14 and six in the one hour delayed scans. The mean contrast ratio for enhancing lesions detected with the triple dose of Gd-DTPA was higher than those for lesions present in both the standard dose (P < 0.0009) and the one hour delayed scans (P = 0.04). These data indicate that with a triple dose of Gd-DTPA many more enhancing lesions can be detected in patients with PPMS. This is important both for planning clinical trials and for detecting the presence of inflammation in vivo in the lesions of such patients.
Adult↗