PubMed Health⌕ Search

Biomedical subjects

C Mainero

Publications and source records attributed to C Mainero.

16 recordsLinked to original sources

Sex hormones modulate brain damage in multiple sclerosis: MRI evidence.

BACKGROUND: Sex related differences in the course and severity of multiple sclerosis (MS) could be mediated by the sex hormones. OBJECTIVE: To investigate the relation between serum sex hormone concentrations and characteristics of tissue damage on conventional magnetic resonance imaging (MRI) in men and women suffering from relapsing-remitting MS. RESULTS: Serum testosterone was significantly lower in women with MS than in controls. The lowest levels were found in women with a greater number of gadolinium enhancing lesions. A positive correlation was observed between testosterone concentrations and both tissue damage on MRI and clinical disability. In men, there was a positive correlation between oestradiol concentrations and brain damage. CONCLUSIONS: The hormone related modulation of pathological changes supports the hypothesis that sex hormones play a role in the inflammation, damage, and repair mechanisms typical of MS.

Adult↗

Enhanced brain motor activity in patients with MS after a single dose of 3,4-diaminopyridine.

BACKGROUND: 3,4-diaminopyridine (3,4-DAP), a potassium (K+) channel blocker, improves fatigue and motor function in multiple sclerosis (MS). Although it was thought to do so by restoring conduction to demyelinated axons, recent experimental data show that aminopyridines administered at clinical doses potentiate synaptic transmission. OBJECTIVE: To investigate motor cerebral activity with fMRI and transcranial magnetic stimulation (TMS) after a single oral dose of 3,4-DAP in patients with MS. METHODS: Twelve right-handed women (mean +/- SD age 40.9 +/- 9.3 years) underwent fMRI on two separate occasions (under 3,4-DAP and under placebo) during a simple motor task with the right hand. FMRI data were analyzed with SPM99. After fMRI, patients underwent single-pulse TMS to test motor threshold, amplitude, and latency of motor evoked potentials, central conduction time, and the cortical silent period; paired-pulse TMS to investigate intracortical inhibition (ICI) and intracortical facilitation (ICF); and quantitative electromyography during maximal voluntary contraction. RESULTS: FMRI motor-evoked brain activation was greater under 3,4-DAP than under placebo in the ipsilateral sensorimotor cortex and supplementary motor area (p < 0.05). 3,4-DAP decreased ICI and increased ICF; central motor conduction time and muscular fatigability did not change. CONCLUSION: 3,4-DAP may modulate brain motor activity in patients with MS, probably by enhancing excitatory synaptic transmission.

4-Aminopyridine↗

Cerebral atrophy in myotonic dystrophy: a voxel based morphometric study.

Brain involvement in myotonic dystrophy type 1 (DM1) is characterised by cortical atrophy and white matter lesions. We compared the magnetic resonance imaging derived grey matter maps of 22 DM1 patients with those of matched, healthy controls using voxel based morphometry to evaluate the extension of global and regional cortical atrophy in DM1, as well as its relationships with clinical and genetic features. Patients had significantly reduced brain tissue volumes. Grey matter volume was inversely correlated with age; this inverse correlation was significantly stronger in DM1 than in controls. Neither the clinical and genetic characteristics nor white matter lesions were correlated with cortical atrophy. Grey matter atrophy was located mainly in the bilateral frontal and parietal lobes, in the bilateral middle temporal gyrus, and in the left superior temporal and occipital gyrus.

Adult↗

Relationship between emotional distress in caregivers and health status in persons with multiple sclerosis.

Caregivers of persons with multiple sclerosis (MS) exhibit less satisfaction with quality of life with respect to the general population. To assess the relationship between depression in caregivers and health status profiles of MS patients, we examined data from 133 patients and their respective caregivers, as a part of a prospective randomized trial aimed to investigate the effectiveness of home-based care. Patients were evaluated at baseline and one year later with measures of physical and psychological impairment and health status (SF-36 Health Survey). Caregivers' psychological morbidity was assessed by the Profile of Mood State (POMS) at the same time points. An improvement of patients' health status as measured in four out of eight SF-36 dimensions was observed over the study period, while psychological morbidity of their caregivers did not change significantly. Depression in caregivers was related to physical, emotional and health status of the patients at baseline and/or at 12-month follow-up. Changes in the degree of depression of caregivers were also associated with changes in disability and health status of the patients. This study confirms and extends in a home-care setting previous findings on relationships between patients' status and depression in caregivers. It suggests that the caregiver is an appropriate and independent target for more focused therapeutic strategies.

Adult↗

A 6-year clinical and MRI follow-up study of patients with relapsing-remitting multiple sclerosis treated with Interferon-beta.

There are few long-term clinical and magnetic resonance imaging (MRI) data on patients treated with interferon-beta (IFN-beta) for relapsing-remitting multiple sclerosis (RRMS). The aim of this study was to provide clinical and MRI data on 68 patients with RRMS treated over a 6-year period and to investigate whether a baseline MRI predicts their long-term clinical and MRI outcome. Six MRI scans were performed monthly before treatment and a further 13 scans were performed during treatment with IFN-beta, the last of which 6 years after commencement of treatment. The relapse rate, disability as measured by the Expanded Disability Status Scale (EDSS), and MRI parameters, including Gd-enhancing lesion load (Gd-LL), T2 hyperintense lesion load (T2-LL) T1 hypointense lesion load (T1-LL) and supratentorial brain volume (SBV) were measured throughout the study. The mean annual relapse rate over the 6 years was 0.52 (SD 0.67), which is significantly lower (68.6%) than the mean annual relapse rate of 1.6 observed during the 2-year period before the commencement of treatment (P < 0.01). The median EDSS score increased from 2 to 2.5, remaining stable in 60% of the patients. From the baseline scan to the final scan, there was a median increase of 7% in the T2-LL and 23.9% in the T1-LL, whilst SBV decreased by 2.7%. The increase in the EDSS over the course of the study was significantly correlated with a reduction in brain volume (r = 0.46, P = 0.001). Greater brain damage at baseline, as measured by both T2-LL and T1-LL, was significantly associated with an increase in disability over the 6 years (r = 0.44, P = 0.0009; r = 0.50, P = 0.0007, respectively). This study shows a sustained effect of IFN-beta on the relapse rate, which is lower than during the 2 years before treatment commencement. More than half the patients showed an improvement or stabilization in the EDSS score. The increment in disability was correlated with the development of brain atrophy but not with increases in lesion burden. Finally, the finding that the extent of lesion burden at the baseline was a strong predictor of increasing disability suggests that IFN-beta treatment might have a moderate effect in modifying the multiple sclerosis (MS) disease course over 6 years unless preventive treatment is started early.

Adjuvants, Immunologic↗

MRI brain volume changes in relapsing-remitting multiple sclerosis patients treated with interferon beta-1a.

The aim of this study was to investigate changes of brain volume as measured by magnetic resonance imaging (MRI) in relapsing-remitting multiple sclerosis (MS) patients under treatment with interferon beta-1a. Moreover, the relationship between brain volume changes and standard MR or clinical outcome variables was determined. After a 6-month pretreatment period, 52 patients with relapsing-remitting MS were assigned to receive interferon beta-1a (Rebif-Serono) during a 24-month treatment period MRI scans were performed monthly during the 6-month pretreatment period and for the first 9 months of the treatment period. A final MRI scan was also performed at the end of the 12- and 24-month treatment period. Over 24 months of IFNbeta-1a treatment, a significant decrease of hyperintense lesion volume was found (-18.0%; p<0.0001) compared to the last pretreatment scan, while T1 hypointense volume showed a slight nonsignificant increase (+2.2%), and brain volume showed a significant decrease (-2.2%; p<0.0001). The mean volume of enhancing lesions over the 6-month pretreatment period was significantly related to absolute (p=0.02; r=-0.32) and per cent change (p=0.03; r=-0.30) of brain volume during 24-month treatment period. No correlations between changes in brain volume and changes in T2 hyperintense volume or T1 hypointense volume were observed. Neither was there a relationship between brain volume and changes of Expanded Disability Status Scale (EDSS) or frequency in clinical relapses. Of the group in whom was detected a significant decrease of brain volume, 13 out of 26 (50%) had a sustained change in EDSS while in the group that did not have a significant decrease of brain volume, only 3 out of 26 (11.5%) had a sustained EDSS change (p=0.02). In this study a decrease of brain volume was found in relapsing-remitting MS patients treated with IFNbeta-1a over 2 years. The only parameter that predicted brain volume decrease by 2 years of IFNbeta-1a treatment was the mean volume of enhancing lesions over the 6-month pretreatment period.

Adolescent↗

Correlates of MS disability assessed in vivo using aggregates of MR quantities.

OBJECTIVES: To assess the magnitude of the correlations between disability and composite MRI scores in patients with MS. METHODS: T2- and T1-weighted MRI, magnetization transfer imaging, diffusion tensor imaging, and MRS imaging scans of the brain from 23 patients with MS were obtained. T2 lesion volume, T1 lesion volume, brain magnetization transfer ratio, average brain diffusivity (D), and brain N-acetylaspartate/creatine ratio were measured. RESULTS: The correlations between the Expanded Disability Status Scale (EDSS) score and each of the MR quantities taken in isolation were not significant, with the exception of the correlation between EDSS and the NAA/creatine ratio (r = -0.50; p = 0.01). In contrast, three of the composite MR scores computed using regression models were strongly correlated with the EDSS scores (r range, 0.58 to 0.73; p range, 0.004 to 0.0001). The model that included T2 and T1 lesion volumes and brain D explained 34% of the EDSS variance; the model that included T2 and T1 lesion volumes and brain N-acetylaspartate/creatine ratio explained 36% of the EDSS variance; the model that included T1 lesion volume, brain D, and brain N-acetylaspartate/creatine ratio explained 53% of the EDSS variance. CONCLUSIONS: The results suggest that multiparametric MR models have the potential to provide powerful measures to monitor MS evolution.

Adult↗

Brain atrophy in relapsing-remitting multiple sclerosis: relationship with 'black holes', disease duration and clinical disability.

Recent MRI studies in multiple sclerosis have highlighted the potential role of brain atrophy evaluation as a putative marker of disease progression. In the present study, we evaluated the supratentorial and infratentorial brain volume in patients with relapsing remitting multiple sclerosis (RR MS) and in healthy subjects. Moreover, we determined whether brain volumes of MS patients are associated with different aspects of brain MRI abnormalities and clinical findings. Two-dimensional acquired MRI was performed on 52 relapsing-remitting multiple sclerosis and 30 healthy subjects. The volume of supratentorial and infratentorial structures was measured in selected representative slices. Gd-enhancement, T2 hyperintense, T1 hypointense (i.e. 'black holes') total lesion load, as well as the area of corpus callosum was calculated in the MS group and related to brain volume measures. Correlations between MRI parameters and clinical features were also considered. MS patients had significantly lower supratentorial, infratentorial brain volume and corpus callosum area than healthy subjects (P<0.01). Supratentorial brain volume was significantly related to corpus callosum area (r=0.58; P<0.01) and T1 hypointense lesion load (r=0.48; P<0.01), but not with T2 hyperintense lesion load. Infratentorial/supratentorial ratio was significantly associated with disease duration and EDSS score (r=-0.34; P=0.02 and r=-0.49; P<0.01, respectively). This study documents that brain atrophy is an early MRI finding in RR MS and it is closely related to 'black holes' burden. The use of relative values (infratentorial/supratentorial ratio) may increase the conspicuity of correlation between clinical and MRI findings.

Adolescent↗

Antinuclear antibodies and response to IFNbeta-1a therapy in relapsing-remitting multiple sclerosis.

We determined whether positive ANA was related to response to rIFNss-1a in 62 relapsing-remitting MS patients. According to the presence of antinuclear antibodies (ANA) at baseline and during the first 6 months of treatment, patients were sorted in different groups. The clinical and MRI outcome during short-term (6 months) and long-term (24 months) treatment period was not statistically different between the groups. Therefore, the response to IFNbeta-1a seems not to be influenced by ANA occurrence either before or during treatment. When the analysis was extended to other autoantibodies (i. e. antithyroid, anticardiolipin) similar results were obtained.

Adjuvants, Immunologic↗

MRI in multiple sclerosis during the menstrual cycle: relationship with sex hormone patterns.

We investigated MRI activity in MS during the menstrual cycle in relation to physiologic sex hormone fluctuations. Eight women with relapsing-remitting MS were submitted to serial brain gadolinium-enhanced MRI examinations over a 3-month period in two alternate follicular and luteal phases of the menstrual cycle. The ratio of progesterone/17-beta-estradiol during the luteal phase was significantly associated with both number (r = 0.6, p = 0.03) and volume (r = 0.7, p = 0.009) of enhancing lesions, providing support for a role of these hormones as immunomodulatory factors in MS.

Adult↗

Fatigue and magnetic resonance imaging activity in multiple sclerosis.

Fatigue is a frequent and often severe symptom in multiple sclerosis. Pathogenic mechanisms proposed for fatigue include the release of proinflammatory cytokines, which is thought to have an important effect on changes in the blood-brain barrier (BBB). To investigate whether fatigue is related to BBB disruption we studied 11 relapsing-remitting MS patients participating in a multicenter longitudinal study comparing the sensitivity of monthly enhanced magnetic resonance imaging (MRI) after standard-dose and triple-dose injection of gadolinium-diethylene triaminopentoacetic acid (Gd-DTPA). Serial Gd-enhanced MRI studies were performed in two separate sessions every 4 weeks for 3 months. An expanded version of the Fatigue Severity Scale, including 29 items, was administered 24 h before each MRI examination. No relationship was found between the number and volume of Gd-enhancing lesions and fatigue scores at any monthly examination over the study period. Furthermore changes in MRI activity were not significantly related to changes in fatigue scores. These results were obtained on triple-dose delayed scanning, which is more sensitive than standard-dose scanning in detecting areas of BBB disruption. Our preliminary results thus do not support the hypothesis of a relationship between BBB alterations and fatigue severity in multiple sclerosis.

Adult↗

Magnetic resonance outcome of new enhancing lesions in patients with relapsing-remitting multiple sclerosis.

The aim of the study was to monitor the natural history of new enhancing lesions in multiple sclerosis (MS) by means of serial gadolinium-enhanced magnetic resonance imaging (MRI). Out of the 63 new enhancing lesions seen on the baseline scan, belonging to 26 relapsing-remitting MS patients, 26 (40%), nine (14%) and four (6%) lesions showed persisting enhancement at first, second and third follow-up scan, respectively. At the end of 5 months of follow-up, 58 (92%) of the new enhancing lesions were detected as T2 hyperintensities, 24 (38%) as T1 hypointensities ('black holes'), and five lesions (8%) disappeared in both T2 and T1 weighted images. Duration of gadolinium enhancement of at least two consecutive scans significantly influenced the development of 'black holes'. No significant correlation was observed between volume, location, configuration of enhancement at baseline and final outcome of the lesion. In individual cases, different evolution of new enhancing lesions was observed at the same time. In conclusion, this study documented that different outcomes of new lesions are unrelated either to the individual patient or to the baseline MRI characteristics. However, prolonged blood-brain-barrier disruption as shown by persisting enhancement significantly influences the lesion outcome.

Adolescent↗

Functional correlates of repeated administration of cocaine and apomorphine in the rat.

The [14C]2-deoxyglucose method was applied to measure the effects of repeated (8 consecutive days) administration of apomorphine (0.5 mg/kg/day s.c.) or cocaine (15 mg/kg/day i.p.) on cerebral glucose utilization in freely moving rats. Altered rates of glucose utilization were measured in extrapyramidal motor areas, such as the globus pallidus, entopeduncular nucleus, subthalamic nucleus, substantia nigra and lateral habenula of both cocaine- and apomorphine-treated rats. Furthermore, cocaine-treated animals displayed increased glucose metabolism in the mesolimbic dopaminergic projections, such as nucleus accumbens and olfactory tubercle, and in the hippocampus. These results suggest that altered functional activity within the dopaminergic mesolimbic system may play a role in the process of sensitization to psychomotor stimulant drugs.

Animals↗