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M Rovaris

Publications and source records attributed to M Rovaris.

121 records · Page 7Linked to original sources

Patterns of disease activity in multiple sclerosis patients: a study with quantitative gadolinium-enhanced brain MRI and cytokine measurement in different clinical subgroups.

In this study we assessed the subclinical disease activity in 45 patients with primary progressive, secondary progressive or relapsing-remitting multiple sclerosis (MS). The patients had gadolinium-enhanced brain MRI scans, which were analysed using a semiquantitative method both for lesion load and for degree of enhancement. At the same time cerebrospinal fluid (CSF) and serum samples were collected and, from these, cytokine levels were measured in most cases by enzyme-linked immunoassay using commercially available kits. Enhancing lesions on MRI were found in 73% of the patients. The sensitivity of this test was greatly increased by our method of analysis as far as the primary progressive patients are concerned (70% vs 40% for conventional evaluation). CSF interleukin-1 beta (IL-1 beta) levels were above the normal range in 22% and IL-6 levels in 13% of patients, while tumour necrosis factor alpha (TNF-alpha) was undetectable or below the upper normal limits in all the samples tested. Serum IL-1 beta was above the normal limits in 40%, IL-6 in 42% and TNF-alpha in 7% of patients. No significant differences in cytokine profiles were found between the clinical subgroups. This study confirms the high sensitivity of gadolinium-enhanced MRI in detecting MS activity, which was further increased by our method of analysis. Longitudinal studies performed with more sensitive immunological techniques are needed to define better the relationship between cytokine, clinical and MRI data in MS patients.

Adult↗

Magnetic resonance in monitoring the natural history of multiple sclerosis and the effects of treatment.

In this review the main contributions of magnetic resonance (MR) techniques in the monitoring of multiple sclerosis (MS) course, both natural or modified by treatments, are presented. MR measures well correlate with short-term disease evolution and therefore their use is appropriate as primary end-points in preliminary clinical trials evaluating the effects of new treatments. In contrast, the correlation between MR measures and long-term clinical evolution in clinically definite MS is less clear, thus indicating that such measures can be used at present only as a secondary end-point in large scale definitive trials. The results coming from the clinical application of newer MR techniques with higher pathological specificity are also presented and their possible future roles in monitoring treatment aimed at preventing development of disability in MS are discussed.

Brain↗

Semi-automated thresholding technique for measuring lesion volumes in multiple sclerosis: effects of the change of the threshold on the computed lesion loads.

Quantitative evaluation of lesion load in multiple sclerosis (MS) from magnetic resonance imaging (MRI) scans is becoming important in understanding and monitoring the progression of the disease. Methods of MS lesion segmentation based on intensity thresholding offer one of the most robust and easily-implemented means of computing the total lesion volume. This study evaluated the effects of slight changes in the choice of intensity threshold on computed lesion volumes in 20 patients with MS using such a technique. After judging the optimum choice of threshold value, the threshold value was increased and decreased by 3% in 1% steps around this value; we observed a mean change of 15% in computed lesion volumes for 1% changes of threshold value. Larger changes in lesion volume were found when the threshold was changed by larger amounts. On the other hand, the amount of time required for manual review decreased, and the confidence with which manual review could be performed increased when using lower thresholds. This study shows that the choice of threshold is a crucial factor in measuring lesion volumes in MS when using intensity-based techniques. It also suggests that in multicenter and/or longitudinal studies, criteria for choosing the threshold should be developed whereby the threshold level should be set such that all MR visible lesions are above it, in order to minimise the human interaction and, consequently, the reproducibility of the results.

Brain↗

Cardiac autonomic function during sleep and wakefulness in multiple sclerosis.

Some studies in multiple sclerosis (MS) patients have shown evidence of autonomic dysfunction involving the cardiovascular system. However, the findings in these studies have not been completely consistent. The discrepancy may be related to the limits of the traditional autonomic tests during wakefulness. In our study, after the investigation of the cardiovascular reflexes during wakefulness, heart rate (HR) variations were considered during sleep in order to avoid the limits of cooperation and the emotional state of the patient. We evaluated tonic (vagal activity) HR modifications in relation to the deepening of sleep, as well as phasic (sympathetic activity) HR modifications in relation to spontaneous body movements during sleep, in 25 MS patients and 25 age-matched controls. No difference was found between the two groups in autonomic function during wakefulness. A reduced parasympathetic activity was observed in MS subjects during both rapid eye movement (REM) and non-REM sleep, while no difference was found in sympathetic function between patients and controls. No significant correlation was found between cardiac autonomic data during sleep and MRI lesion load in the infratentorial areas and, in particular, of the brain stem. The findings of our study suggest that autonomic nervous system evaluation during sleep could show impairment earlier than the traditional autonomic tests during wakefulness.

Adult↗

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↗

Acute transverse myelopathy: spinal and cranial MR study with clinical follow-up.

PURPOSE: To evaluate the contribution of MR in determining the cause of acute transverse myelopathy, to determine the frequency and types of the intracranial lesions detectable on MR at the onset of the disease, and to monitor clinical and MR evolution of the disease. METHODS: Spinal and cranial MR images were obtained for 30 patients with acute transverse myelopathy. Gadopentetate dimeglumine was administered in 10 patients. Mean follow-up time was 18 months. RESULTS: Spinal cord MR findings were abnormal in 14 of 30 patients. The abnormal MR can be divided into group A, in which one segment was involved (8 patients), and group B, in which more than one segment was involved (6 patients). In both groups there were 2 patients with enhancing lesions. Enhancement was less homogeneous in the group B patients. Enhancement did not change with increased length of lesion. At follow-up, the diagnostic categories of the patients were multiple sclerosis (8 patients), encephalomyelitis (1 patient), viral myelitis (3 patients), and myelopathy of unknown cause (18 patients). After the episode of acute transverse myelopathy, in 4 of 8 patients in group A and in 4 of 5 patients with normal spinal MR but abnormal brain MR findings clinical signs of multiple sclerosis developed. In no patients in group B did multiple sclerosis develop. The final diagnoses for the 4 patients with gadolinium-enhancing spinal lesions were myelopathy of unknown cause (2 patients), multiple sclerosis (1 patient), and viral myelitis (1 patient). CONCLUSION: MR contributed to establishing the diagnosis in 40% of our cases.

Acute Disease↗

Nocturnal sleep study in multiple sclerosis: correlations with clinical and brain magnetic resonance imaging findings.

It has been suggested that sleep disturbances in multiple sclerosis (MS) may be related to periodic leg movements (PLM) during sleep, but to date polysomnographic studies were conducted only on small and unselected patient groups. Aim of this study was to evaluate 8-hour polysomnography in MS patients and to correlate sleep results with clinical and brain magnetic resonance imaging (MRI) data. Twenty-five clinically definite MS patients, without mood disorders and drug-free, entered the study. The patients were compared to 25 age- and sex-matched subjects. MS patients had significantly reduced sleep efficiency and experienced more awakenings during sleep. No difference was found in sleep architecture parameters between MS patients and controls. PLM was found in 9 patients (36%) and 2 controls (8%; p = 0.02). Of the six patients who complained of insomnia two had PLM and 2 others presented with PLM and central sleep apnea. In patients with PLM greater MRI lesion loads were detected in the infratentorial regions, particularly in cerebellum and brainstem. Larger studies in neurological diseases that produce focal lesions in these brain areas could provide useful information on the PLM pathogenesis.

Adult↗

Brain magnetic resonance imaging correlates of cognitive impairment in multiple sclerosis.

We evaluated the correlations between cognitive impairment, clinical and brain magnetic resonance imaging (MRI) findings in 100 patients with multiple sclerosis (MS). The performance on one or more neuropsychological tests was abnormal in 47% of the 64 patients who completed the entire neuropsychological battery; the cognitive impairment was mild in 14 (22%) and severe in 16 (25%). Performance on any single neuropsychological test was unrelated to clinical parameters (age, duration of the disease, disability). The neuropsychological performance of relapsing-remitting patients was better than in patients with a chronic-progressive disease. The mean scores for almost all the neuropsychological tests were significantly lower in patients with severe ventricular dilatation and corpus callosum atrophy than in patients in whom these structures were little affected. Mean scores for WMS, performance Intelligence Quotient (IQ), total IQ and Token Test (TT) were also significantly correlated with the widening of cortical sulci and total lesional scores. Our data support the contention that the involvement of pathways that are critical for a given cognitive process as well as the progression of the axonal degeneration and sclerosis seem to play important roles in the pathophysiology of cognitive dysfunction in MS.

Adult↗

Brain stem magnetic resonance imaging and evoked potential studies of symptomatic multiple sclerosis patients.

In this study we evaluated the sensitivity of neuroradiological and neurophysiological tests for detecting brain stem (BS) lesions in multiple sclerosis patients, since the recent introduction of the gradient motion rephasing technique has markedly increased the image quality of magnetic resonance imaging (MRI). From 50 MS patients (33 women and 17 men; mean age 35.9 +/- 8.3 years; mean duration of the disease 7.2 +/- 4.1 years) with clinical signs of BS involvement, brain MRI, BS auditory evoked potentials (BAEPs), and left and right median somatosensory evoked potentials (mSEPs) were obtained. BS MRI lesions were detected in 41 patients (82%); in 14 cases they were located in the medulla oblongata, in 55 in the pons, and in 24 in the midbrain. Single lesions were present in 20 patients, while two or more BS lesions were demonstrated in 21 patients; 30 patients had at least one lesion located close to the inner or the outer cerebrospinal fluid border. BAEPs were abnormal in 19 of the 50 patients (38%), and BS components of mSEPs were abnormal in 15 of 46 (33%). With combined use of these neurophysiological techniques, BS abnormalities were revealed in 24 patients (48%). Only 1 patient had neurophysiological BS abnormalities and normal MRI. Moreover, there was a good correlation (74%) between the clinical and MRI BS findings in the 23 patients with signs referable to focal neurological BS lesions. The concordances considering clinical and evoked potential reports were positive, but less marked.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pattern visual evoked potential mapping in Alzheimer's disease: correlations with visuospatial impairment.

We evaluated pattern visual evoked potentials (PVEPs) in patients with Alzheimer's disease (AD) and correlated the neurophysiological results with visuospatial performances in order to understand better the underlying causes of visual disturbances. Latencies and topographical distribution of PVEP components were evaluated in 20 AD patients who underwent an extensive battery of neuropsychological tests. Mean latencies of N70 and P100 were normal in AD patients, while mean latencies of N140 and P200 were significantly increased in comparison with age-matched healthy controls. The topographical distribution of PVEP components did not show any significant difference between the two groups. Visuospatial impairment was detected in 8 patients (40%). Statistically significant positive correlations were observed between P200 amplitude (posterior right hemisphere mean z score) and performance in visuospatial tests. Our data are consistent with a sparing of foveal retinocortical pathways and with the selective dysfunction of either corticocortical connections between the striate cortex and the visual associative structures or of right temporo-parieto-occipital visual analyzers.

Age of Onset↗

Prognostic value of MR and magnetization transfer imaging findings in patients with clinically isolated syndromes suggestive of multiple sclerosis at presentation.

BACKGROUND AND PURPOSE: The extent of abnormalities on T2-weighted MR images of the brain of patients with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) at presentation is associated with an increased risk of developing clinically definite MS (CDMS). We evaluated whether subtle changes outside T2-visible lesions are present in the brain of these patients and whether their extent increases the risk of subsequent development of CDMS. METHODS: Dual-echo, T1-weighted, and magnetization transfer (MT) images of the brain were obtained from 24 patients with CIS at presentation. These patients were followed up for a mean period of 33 months (range, 25-42 months). Twenty age- and sex-matched healthy volunteers served as control subjects. To create MT histograms of the normal-appearing brain tissue (NABT), macroscopic lesions were segmented from dual-echo images, were superimposed automatically, and were nulled out from the coregistered and scalp-stripped MT ratio (MTR) maps. The following MTR histogram-derived measures were considered: average MTR, MTR(25), MTR(50), MTR(75), peak height, and peak position. T2 and T1 lesion loads, average lesion MTR, and brain volume were also measured. RESULTS: Patients with CIS had lower average NABT-MTR (P < .0001) and peak position (P = .002) than did control volunteers, but patient brain size was similar to that of volunteers. At follow-up, 10 (41%) patients developed CDMS. Patients who developed CDMS during the follow-up period had higher T2 lesion volume (P = .003) and lower average NABT-MTR (P = .005) and peak position (P = .006) than did those who did not develop CDMS. T2 lesion volume (odd ratio, 3.54; P = .0005) and average NABT-MTR (odd ratio, 0.81; P = .01) were independent predictors of the subsequent development of CDMS. CONCLUSION: Subtle changes occur outside lesions visible on conventional MR images among patients with CIS suggestive of MS at presentation. The greater the extent of such abnormalities is, the higher is the risk of subsequent development of CDMS.

Adult↗

[In-vivo assessment of multiple sclerosis pathology: the role of neuroimaging techniques].

Although the correlations between magnetic resonance imaging (MRI) findings and long-term disease evolution range from poor to moderate', conventional pre- and post-contrast MRI provides sensitive and reliable measures to monitor multiple sclerosis (MS) activity over time. The application of non-conventional techniques, such as magnetization transfer imaging (MTI), proton magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI), can increase the pathological specificity of MRI findings and, as a consequence, improve the relationship with the clinical evolution of the disease. These techniques also enable us to quantify the subtle abnormalities occurring in the so-called normal-appearing white matter, thus allowing to achieve a more accurate assessment of MS burden. Some of the aforementioned techniques have already shown their value for assessing MS dynamics, whereas other still need to go through a more complete validation process prior to any extensive clinical application in MS. The use of multiparametric MRI approaches, including both conventional techniques and new methods able to assess the macro- and microscopic disease burden and to characterize the individual lesion intrinsic nature, should improve our ability to study in vivo the pathology of MS.

Brain↗

Sensitivity of enhanced MR in multiple sclerosis: effects of contrast dose and magnetization transfer contrast.

BACKGROUND AND PURPOSES: New strategies have been developed to improve the sensitivity of contrast-enhanced MR imaging in quantifying disease activity in patients with multiple sclerosis (MS). The goal of the present study was to evaluate the sensitivity of T1-weighted images after injection of a triple dose of contrast material and application of a magnetization transfer (MT) pulse in the detection of enhancing lesions as compared with the conventional approach. METHODS: Monthly MR images were obtained in 13 patients with relapsing-remitting MS for a period of 3 months. The MR studies were performed on two separate occasions with single- and triple-dose contrast material. In each session, T1- and T2-weighted spin-echo images with and without the MT pulse were obtained before and after contrast administration. All images were evaluated in a blinded fashion and scored in random order and consensually by two readers. The number of total and new enhancing lesions and active images was counted. RESULTS: Eighty-six percent more enhancing lesions and 54% more new enhancing lesions were detected with triple-dose as compared with single-dose non-MT sequences, whereas single-dose MT images depicted 33% more enhancing lesions and 18% more new enhancing lesions than the single-dose non-MT images. Twenty-nine percent more lesions were detected on triple-dose non-MT images than on single-dose MT images. The combination of a triple dose of contrast material and MT did not produce any significant change in detection of enhancing lesions as compared with a triple dose of contrast without MT. CONCLUSION: The use of a triple dose of contrast material is the best approach to maximize the sensitivity of enhanced MR imaging.

Adult↗