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Biomedical subjects

V Martinelli

Publications and source records attributed to V Martinelli.

At least 19 recordsLinked to original sources
PubMed1996

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↗
PubMed1996

Clinical and radiologic correlates of a novel T lymphocyte gamma-interferon-activated Ca2+ influx in patients with relapsing-remitting multiple sclerosis.

T lymphocytes are the main cellular mediators in MS pathogenesis, and their activity is modulated by a complex cytokine network in which gamma-interferon (gamma-IFN) is considered essential. We have recently identified a new transplasmalemma Ca2+ influx activated by gamma-IFN in T lymphocytes (mainly CD4+) from patients with MS that makes T cells more susceptible to proliferation. To define the possible role of this Ca2+ influx as a marker of disease activity, we correlated its appearance with clinical and MRI findings in a cross-sectional study of 67 patients with relapsing-remitting MS (RR-MS). We also conducted a short-term longitudinal evaluation (every 15 days over a 5- to 7-month period) in three of the RR-MS patients. Sixty-five percent of all clinically active RR-MS patients showed the gamma-IFN-activated Ca2+ influx. However, positivity was higher in the first week (78%) after the onset of a clinical exacerbation than the second (57%) and third (44%) weeks. The influx was also detected in 45% of clinically stable RR-MS patients, 30% of RR-MS patients with a "benign" course of the disease, 14% of the other active autoimmune or neurologic disease patients, and 9% of healthy subjects (RR-MS versus control subjects, p < 0.001). Brain-MRI gadolinium-enhancing lesions were more frequently found in influx-positive (72%) than in influx-negative (47%) patients (p < 0.005). In the longitudinal study, we recorded five intracellular Ca2+ ([Ca2+]i) elevations and three clinical attacks (one per patient). A peak increase of [Ca2+]i due to the gamma-IFN-activated Ca2+ influx always preceded the clinical attacks from 4 to 45 days and coincided to MRI evidence of inflammation. [Ca2+]i had returned to baseline levels by the time of the onset of two clinical attacks. This finding may account for the lack of detection of the gamma-IFN-activated Ca2+ influx in some RR-MS patients during the first week after clinical onset. The strong association between the influx and clinical and MRI evidence of disease activity supports its role in the early phases of cellular immune activation leading to demyelination in MS. The detection of [Ca2+]i elevations due to the gamma-IFN-activated Ca2+ influx may represent a valuable prognostic marker of disease activity and may be useful to monitor immunologic studies of MS patients in future clinical trials.

Adolescent↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

Source model and scalp topography of pattern reversal visual evoked potentials to altitudinal stimuli suggest that infoldings of calcarine fissure are not part of VEP generators.

Visual evoked potentials (VEPs) to pattern reversal vertical bar stimuli were recorded from 19 scalp, 2 zygomatic and 3 inion derivations referenced to digitally linked earlobes in 50 controls. 1, 2 and 4 cycles per degree (cpd) patterns were presented as full field (FF) stimuli, on upper and lower hemifields (UHF-LHF), upper and lower quadrants and with the occlusion of central and peripheral UHF and LHF. VEPs to octant stimuli were also recorded with 2 cpd patterns. N1, P1 and N2 components were recorded from posterior and inion derivations with FF stimuli, from posterior derivations with LHF stimuli, only from inion leads with UHF stimuli, from derivations ipsilateral to stimuli with quadrants and octants, and from midline derivations only with lower quadrants. Polarity inverted sequences (iP1-iN1-iP2) were recorded from the other scalp derivations, with similar latency and spatial frequency sensitivity as N1-P1-N2. The orientation of Equivalent Dipoles (ED) was orthogonal with surface coordinates of mesial and occipito-polar calcarine cortex, measured on Magnetic Resonance Imaging. A model of VEP generators is proposed, suggesting that the VEP sequence is elicited only in mesial and occipito-polar surfaces of calcarine cortex.

Adult↗
PubMed1995

Brain MRI correlates of cognitive impairment in primary and secondary progressive multiple sclerosis.

Brain magnetic resonance imaging (MRI) and an extensive battery of neuropsychological tests exploring frontal functions, short and long-term memory, visuo-spatial skills, attention and language were applied to 14 patients with primary progressive multiple sclerosis (PPMS) and 17 patients with secondary progressive MS (SPMS). Patients with PPMS and SPMS did not differ in degree of physical disability, but cognitive deficits were found in 9/17 (53%) patients with SPMS and in only 1/14 (7%) of those with PPMS (p = 0.01). Patients with SPMS had higher total (p = 0.004), periventricular (p = 0.008) and non-periventricular (p = 0.04) MRI lesion loads than patients with PPMS. In detail, patients with SPMS had greater involvement of frontal (p = 0.05) and occipital (p = 0.02) horns, trigones (p = 0.04), third ventricle (p = 0.03), basal ganglia (p = 0.02), parietal (p = 0.02), temporal (p = 0.004) and occipital (p = 0.03) lobes. Patients with SPMS and neuropsychological deficits had higher non-periventricular lesion loads than patients with SPMS who did not have such deficits (p = 0.005). Our results indicate that both neuropsychological and brain MRI abnormalities are more extensive in patients with SPMS. Since physical disability was similar for both groups, disability in PPMS may be predominantly due to spinal cord involvement.

Adult↗
PubMed1995

Intra- and inter-observer agreement of brain MRI lesion volume measurements in multiple sclerosis. A comparison of techniques.

The measurement of MRI lesion load in multiple sclerosis is increasingly being used to evaluate the natural history of the disease and to monitor the efficacy of treatments. If, as might occur in multicentre studies, lesion load is measured by several observers in different patients or by the same observer in serial scans, it would be necessary to utilize a technique which provides results with high inter- and intra-observer agreements. This study was performed to evaluate the intra- and inter-observer agreement of semi-automated lesion volume measurement using thresholding, and to compare them with those obtained using an arbitrary scoring system (ASS) and a quantitative manual tracing method (MTM). Brain MRIs were obtained for 20 clinically definite multiple sclerosis patients and were evaluated independently by three observers. The median intra- and inter-observer agreements were, respectively, 88.5% (range 69.0-96.8%) and 79.0% (range 73.3-98.3%) using the ASS, 95.0% (range 85.1-99.4%) and 93.4% (range 77.3-98.3%) for the MTM, 96.3% (range 94.2-98.9%) and 93.7% (range 83.8-98.3%) for the semi-automated technique. The intra- and inter-observer agreements for the semi-automated technique increased to 98.5% (range 96.3-99.8%) and 96.1% (range 90.5-98.6%) when a consensus in the choice of threshold for lesion segmentation was reached. The intra- and inter-observer agreements were significantly greater for the semi-automated method compared with both the arbitrary scoring and the MTMs. The intra-observer variability for the semi-automated technique was significantly lower (P < 0.0001) than the inter-observer variability obtained using the same technique. These data indicate that it is possible to obtain high intra- and inter-observer agreements using a semi-automatic thresholding technique to quantify lesion volumes in multiple sclerosis. The technique may prove useful in multicentre studies, in which a single observer is still preferable.

Brain↗
PubMed1995

Transitional progressive multiple sclerosis: MRI and MTI findings.

Transitional progressive multiple sclerosis (MS) is quite an unusual form of presentation and course of the disease. A case with this progressive form is presented and brain MRI and MTI findings are discussed in relation to the possible insight they may provide for understanding the mechanisms that determine progressive disability in MS.

Adult↗
PubMed1995

A brain MRI study of different types of chronic-progressive multiple sclerosis.

INTRODUCTION: This study was performed to define the pattern of brain magnetic resonance imaging (MRI) abnormalities in chronic-progressive MS (MS). MATERIAL AND METHODS: Brain MRIs were obtained for 17 patients with secondary progressive MS (SPMS), 14 with primary progressive MS (PPMS) and 5 with "transitional" progressive MS (TPMS). RESULTS: Total lesion loads were different for the three groups of patients (p < 0.01). At post-hoc analysis, there was no difference between patients with TPMS and those with PPMS, while both these groups had lesion loads lower than those of patients with SPMS. Patients with PPMS with clinical signs indicating involvement of both brain and spinal cord had greater total lesion loads than those with clinical isolated spinal cord involvement (p < 0.05). CONCLUSION: These data indicate that brain MRI patterns of abnormalities are related to the clinical manifestations in patients with chronic-progressive MS.

Adult↗
PubMed1995

Brain magnetic resonance imaging and multimodal evoked potentials in benign and secondary progressive multiple sclerosis.

Brain MRI and multimodal evoked potentials (EPs) were obtained for 13 patients with benign multiple sclerosis and 13 patients with secondary progressive multiple sclerosis, matched for age and duration of the disease, to investigate the nature of the disability in multiple sclerosis. Patients with secondary progressive multiple sclerosis had significantly greater lesion loads for five of seven periventricular regions and for three of nine regions separate from the ventricles. Patients with secondary progressive multiple sclerosis also had more severe infratentorial atrophy scores (p = 0.04), whereas there were no differences between the two groups in number and extent of enhancing lesions. The frequencies were significantly higher and severities greater for multimodal EP abnormalities of all the modalities in patients with secondary progressive multiple sclerosis. At least one EP component was absent in 12 (92%) patients with secondary progressive multiple sclerosis but in only one patient (8%) with benign multiple sclerosis (p < 0.001). There was neurophysiological evidence for cervical cord involvement in eight (61%) patients with secondary progressive multiple sclerosis and in one with benign multiple sclerosis (p < 0.01). These data indicate that the total amount of lesions, the distribution, and the nature of the pathological process might all account for the development of disability in multiple sclerosis.

Age of Onset↗
PubMed1995

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↗
PubMed1995

A magnetization transfer imaging study of normal-appearing white matter in multiple sclerosis.

We attempted to define the role of subtle changes in the normal-appearing white matter (NAWM) in the development of disability in multiple sclerosis (MS). Twenty-seven clinically definite MS patients with either relapsing-remitting or chronic-progressive courses and 10 sex- and age-matched controls entered the study. For each patient and control, we studied two NAWM areas in the frontal lobe with magnetization transfer imaging (MTI). For patients, we also calculated the MT ratios (MTRs) for three contiguous areas of NAWM progressively further from "isolated" lesions visible on conventional MRI. Frontal NAWM in MS patients had lower mean MTRs than the frontal white matter of the controls (p = 0.02). MTRs in the NAWM adjacent to isolated lesions increased with distance from them to the cortical gray matter (p = 0.04). This pattern was typical for patients with chronic-progressive MS whose MTRs in the first two regions of NAWM adjacent to lesions were lower than those of the same regions of patients with relapsing-remitting MS. This study confirms that there are alterations in the NAWM of MS patients and suggests that such changes might be relevant to the disability in MS.

Adult↗
PubMed1995

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↗
PubMed1994

Similar patterns of V kappa gene usage but different degrees of somatic mutation in hairy cell leukemia, prolymphocytic leukemia, Waldenstrom's macroglobulinemia, and myeloma.

To compare V kappa gene usage and the amount of somatic mutation in rearranged Ig genes from patients with lymphoproliferative disorders, we have polymerase chain reaction-amplified and sequenced a total of 26 V kappa genes from a total of 55 cases. Six sequences were obtained both from six cases of prolymphocytic leukemia (PLL) and from nine cases of hairy cell leukemia (HCL). Seven sequences were obtained both from 11 cases of Waldenström's macroglobulinemia (WM) and 29 cases of multiple myeloma (MM). Eleven different germline genes have been used in this series, indicating a wide but nonrandom usage of germline Ig gene rearrangements in these disorders. Comparison of the nucleotide sequences of V kappa genes obtained from B-cell malignancies with germline V kappa genes shows that somatic mutation is rare in PLL and HCL and common in WM and MM. Analysis of the pattern of mutations suggests that WM and MM are derived from B cells that have been selected by antigen at a relatively late stage of differentiation.

Amino Acid Sequence↗
PubMed1994

Sensitivities and predictive values of paraclinical tests for diagnosing multiple sclerosis.

The sensitivities and predictive values of visual, somatosensory, and brain auditory evoked potentials (EPs), cerebrospinal fluid oligoclonal banding (CSF-OB) and magnetic resonance imaging (MRI) were evaluated for the early diagnosis of clinically definite multiple sclerosis (CDMS). Paraclinical evidence of asymptomatic lesions allows a diagnosis of CDMS. Eighty-two patients in whom MS was suspected but diagnosis of CDMS was not possible entered the study prospectively. Paraclinical examinations were performed at entry. Patients were examined and underwent EPs every 6 months, and MRI yearly. After a mean follow-up of 2.9 years, 28 patients (34%) had developed CDMS (McDonald-Halliday criteria). The initial MRI was strongly suggestive of MS in 19 of these (68%), while 27 (96%) had at least one MS-like abnormality in the initial MRI. CSF-OB and EPs had lower sensitivities. CDMS developed during follow-up in 19 of the 36 patients (53%) who had an initial MRI strongly suggestive of MS but in only 1 of the 25 who had normal MRI when first studied. These results support previous conclusions that MRI is the most sensitive test for detecting white matter asymptomatic lesions, and the most predictive for the diagnosis of CDMS.

Adolescent↗
PubMed1994

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↗
PubMed1994

Influence of clinical variables on neuropsychological performance in multiple sclerosis.

The effects of age, educational level, duration and course of the disease, physical disability and mood status on several cognitive functions (short- and long-term memory, frontal functions, attention, language and visuospatial skills) have been evaluated in 42 multiple sclerosis (MS) patients. The Hamilton Depression Rating Scale (HDRS) scores and a secondary progressive disease course significantly influenced neuropsychological performance. Factorial analysis revealed that indexes of (1) frontal function impairment, (2) long-term verbal memory and language function impairment, and (3) visuospatial short- and long-term memory and visuoperceptive function impairment accounted for 85% of the variance in neuropsychological performance. Only the first factor was significantly related to the presence of depressive symptomatology, as assessed by the HDRS. These results indicate that both the course of the disease and the presence of affective disorders must be taken into account when evaluating the natural history of cognitive impairment in MS and suggest that depressive symptomatology and cognitive dysfunction in MS are related to the involvement of at least partially overlapping anatomofunctional circuits.

Adult↗