Biomedical subjects

Federica Agosta

Publications and source records attributed to Federica Agosta.

10 recordsLinked to original sources

PubMed2007

Influence of body segment position during in-phase and antiphase hand and foot movements: a kinematic and functional MRI study.

Behavioral studies have provided important insights into the mechanisms governing interlimb coordination. In this study, we combined kinematic and functional magnetic resonance imaging (fMRI) analysis to investigate the brain cortical and subcortical areas involved in interlimb coordination and the influence of direction of movement and of body segment position on the activity of those areas. Fifteen right-handed healthy subjects were studied while performing cyclic in-phase and antiphase hand and foot movements with the dominant, right limbs, with the upper limb positioned either prone or supine, and in front or behind with respect to the trunk. When contrasting antiphase to in-phase movements, fMRI analysis demonstrated an increased recruitment of a widespread sensorimotor network (including regions in the frontal and parietal lobes, bilaterally, the cingulated motor area, the thalami, the visual cortex, and the cerebellum) considered to function in motor, sensory, and multimodal integration processing. When contrasting the anterior to the posterior position of the upper limb with respect to the trunk, we found different recruitment patterns in the frontal and parietal regions as well as the preferential recruitment of the basal ganglia, the insula, and the cerebellum during the first condition and of regions located in the temporal lobes during the second one. Different brain areas are engaged at a different extent during interlimb coordination. In addition to the relative difficulty of the movement, the different cognitive and sensorial loads needed to control and perform the motor act might be responsible for these findings.

Adult↗

PubMed2007

fMRI changes in relapsing-remitting multiple sclerosis patients complaining of fatigue after IFNbeta-1a injection.

If fatigue in multiple sclerosis (MS) is related to an abnormal activation of the sensorimotor brain network, the activity of such a network should vary with varying fatigue. We studied 22 patients treated with interferon beta 1a (IFNbeta-1a; Avonex, Biogen, Cambridge, MA) with no fatigue (10) and with reversible fatigue (12). fMRI examinations were performed: 1) the same day of IFNbeta-1a injection (no fatigue; entry), 2) the day after IFNbeta-1a injection (fatigue; time 1), and 3) 4 days after IFNbeta-1a injection (no fatigue; time 2). Patients performed a simple motor task with the right, clinically unaffected hand. At time 1, compared with entry and time 2, MS patients with reversible fatigue showed an increased activation of the thalamus bilaterally. In MS patients without fatigue thalamus was more activated at entry than at time 1. In both groups at entry the primary SMC and the SMA were more activated than at times 1 and 2. At entry and time 1, when compared to patients with reversible fatigue, those without showed increased activations of the SII. Conversely, patients with reversible fatigue had increased activations of the thalamus and of several regions of the frontal lobes. An abnormal recruitment of the fronto-thalamic circuitry is associated with IFNbeta-1a-induced fatigue in MS patients.

Adjuvants, Immunologic↗

PubMed2006

Magnetization transfer MRI metrics predict the accumulation of disability 8 years later in patients with multiple sclerosis.

In multiple sclerosis, the relationship between conventional MRI findings and the clinical evolution of the disease is weak. Magnetization transfer (MT) MRI can provide markers reflecting the more disabling features of multiple sclerosis pathology. The aim of the present study was to assess the value of MT MRI quantities and their short-term changes in predicting the long-term accumulation of disability in multiple sclerosis patients. Conventional and MT MRI scans of the brain were obtained at baseline and after 12 months in 73 patients, who were followed prospectively with clinical visits for a median period of 8 years. At baseline and at 12 months, T2-hyperintense and T1-hypointense lesion volume, normalized brain volume [with grey (GM) and white matter (WM) fractions] and average lesion MT ratio (MTR) were measured. At the two time points, metrics derived from the MTR histograms of the whole-brain parenchyma, GM and normal-appearing WM were also computed. A multivariate analysis, adjusted for follow-up duration, was performed to establish which variables were significant predictors of long-term neurological deterioration. At the end of follow-up, 44 patients (60%) showed a significant disability worsening. A multivariable model included baseline GM MTR histogram peak height [P = 0.029, odds ratio (OR) = 0.97], and average lesion MTR percentage change after 12 months (P = 0.016, OR = 0.88) as independent predictors of disability worsening at 8 years (r2 = 0.28). The discriminating ability of such a model in predicting the individual patients' outcome was 66%. MT MRI provides useful prognostic markers for the prediction of the long-term evolution of multiple sclerosis. This study also suggests that GM damage is one of the key factors associated with disability accumulation in this 'white matter' condition.

Brain↗

PubMed2006

MRI criteria for dissemination in space in patients with clinically isolated syndromes: a multicentre follow-up study.

BACKGROUND: The McDonald International Panel accepted the Barkhof/Tintoré criteria for providing MRI evidence of dissemination in space to allow a diagnosis of multiple sclerosis in patients with clinically isolated syndromes (CIS). We applied these criteria in a large cohort of patients with CIS, representative of those seen in a general diagnostic setting, to assess their accuracy in predicting conversion to definite multiple sclerosis and to identify factors that affect this risk. METHODS: In a collaborative study of seven centres, baseline MRI and clinical follow-up data for 532 patients with CIS were studied, with the development of a second clinical event used as the main outcome. All scans were scored for lesion counts and spatial lesion distribution to assess the fulfilment--ie, at least three out of four--of the Barkhof/Tintoré criteria. We used survival analysis and 2x2 tables to assess the test characteristics of the criteria at baseline. FINDINGS: Overall conversion rate was 32.5% with a median survival time of 85.3 months. Fulfilment of the criteria at baseline showed, after a survival time of 2 years, a conversion rate of about 45% (95% CI 37-53) versus about 10% (6-16) in those with no asymptomatic lesions at baseline (p<0.0001). For patients with a follow-up of at least 2 years, the fulfilment of the MRI criteria showed an accuracy of 68% (sensitivity 49%, specificity 79%) for predicting conversion and an increase in risk of nearly four times for conversion compared with those not fulfilling the criteria (odds ratio 3.7, 95% CI 2.3-5.9; p<0.0001). Cox proportional hazards regression analysis accorded with this increased risk. No effects were recorded on the performance of the criteria by sex, presenting symptoms, or centre. Age at baseline did have a small but significant effect as predictor (hazard ratio 0.97, 0.95-0.99; p=0.002), but did not affect the prognostic value of the MRI criteria. INTERPRETATION: MRI abnormalities have important prognostic value. The cut-off, based on the Barkhof/Tintoré criteria, as incorporated in the McDonald diagnostic scheme yields acceptable specificity, but could have lower sensitivity than previously reported.

Adolescent↗

PubMed2005

The level of spinal cord involvement influences the pattern of movement-associated cortical recruitment in patients with isolated myelitis.

Using fMRI, an increased recruitment of the ipsilateral primary sensorimotor cortex (SMC), supplementary motor area, and middle frontal gyrus has been detected in patients with cervical cord myelitis of possible demyelinating origin. The aim of this study was to evaluate, using fMRI, whether the level of cord involvement influences cortical reorganization by comparing patients with isolated myelitis of the cervical and the dorsal portions of the cord, and to investigate whether the extent of cortical reorganization is associated with the extent of cervical cord pathology measured using magnetization transfer (MT) MRI. We studied 24 right-handed patients (14 with a previous involvement of the cervical cord and 10 with an involvement of the dorsal cord) in a chronic and clinically stable phase following an isolated myelitis of possible demyelinating origin and 15 sex- and age-matched healthy controls. During a single session, we obtained fMRI during repetitive flexion-extension of the last four fingers of the right and left hands and cervical cord MT MRI. Average cord MTR was lower in patients with cervical (P < 0.0001) and dorsal (P = 0.0001) myelitis than in controls. Compared to controls and for both tasks, patients with myelitis had an increased recruitment of the ipsilateral primary SMC, which was independent of the level of cord involvement. On the contrary, patients with cervical myelitis had a more widespread recruitment of frontal and parietal regions, whereas those with dorsal myelitis had a more widespread recruitment of temporal and cerebellar regions. Strong correlations (r values ranging from -0.72 to -0.88) were found between relative activations of cortical areas and the severity of cervical cord damage. Patients with isolated myelitis have different patterns of movement-associated cortical activations according to the level of cord involvement. This "level-dependent" functional reorganization of the cortex is likely to have an adaptive role in limiting the clinical outcome of cord damage and should be considered when designing rehabilitation strategies for these patients.

Adult↗

PubMed2005

An fMRI study of the motor system in patients with neuropsychiatric systemic lupus erythematosus.

Functional cortical changes have been demonstrated in patients with several neurological conditions, including stroke, tumors and MS. The correlation found between the extent of fMRI activations and the extent and severity of brain structural damage suggests an adaptive role of these functional changes. In this study, we assess, using fMRI, the brain pattern of movement-associated cortical activations in neuropsychiatric systemic lupus erythematosus (NPSLE) patients and investigate whether the extent of cortical reorganization is associated with the extent of brain pathology, measured on dual-echo and diffusion tensor (DT) MR images. From 14 right-handed NPSLE patients and 14 matched controls, we obtained: (a) fMRI during the performance of repetitive flexion-extension of the last four fingers of the right hand; (b) dual-echo and (c) pulsed-gradient spin-echo echo-planar sequence to calculate DT MRI maps of the normal-appearing white (NAWM) and gray (NAGM) matter. Brain T2-visible abnormalities were detected in 11 NPSLE patients. Compared with controls, NPSLE patients had significantly higher NAWM fractional anisotropy histogram peak height (P = 0.005), and more significant activations of the contralateral primary sensorimotor cortex, putamen and dentate nucleus. They also had more significant activations of several regions located in the frontal and parietal lobes as well as of MT/V5 and the middle occipital gyrus, bilaterally. Strong correlations (r values ranging from 0.79 to 0.87) were found between relative activations of sensorimotor areas and the extent and severity of brain damage. Movement-associated functional cortical changes do occur in patients with NPSLE and might contribute to the maintenance of their normal functional capacities.

Adult↗

PubMed2005

Mean diffusivity and fractional anisotropy histogram analysis of the cervical cord in MS patients.

The spinal cord is frequently involved in multiple sclerosis (MS), and cord damage may be an important contributor to disability. Diffusion tensor magnetic resonance imaging (DT-MRI) provides quantitative information about the structural and orientational features of the central nervous system. In order to assess whether diffusion tensor-derived measures of cord tissue damage are related to clinical disability, mean diffusivity (MD) and fractional anisotropy (FA) histograms from the cervical cord were acquired from a large cohort of MS patients. Diffusion-weighted sensitivity-encoded (SENSE) echo planar images of the cervical cord, and brain dual-echo and diffusion-weighted scans were acquired from 44 patients with MS and 17 healthy controls. Cord and brain MD and FA histograms were produced. An analysis of variance model, adjusting for cord volume and patient age, was used to compare cord DT-MRI parameters from controls and patients. A multivariate linear regression model was used to identify DT-MRI variables independently associated with disability. Average cervical cord FA was significantly lower in MS patients compared to controls. Cord cross-sectional area, average FA and average MD were all significantly correlated with the degree of disability (r values ranging from 0.36 to 0.51). The multivariate linear regression model retained average cord FA and average brain MD as variables independently associated with disability, with a correlation coefficient of 0.73 (P < 0.001). DT-MRI reveals a loss of cervical cord tissue structure in MS patients. The strong correlation found between a composite DT-MRI score and disability suggests that a full and accurate assessment of cervical cord damage in MS provides information that usefully contributes to an explanation of the clinical manifestations of the disease.

Adult↗

PubMed2005

Immunological patterns identifying disease course and evolution in multiple sclerosis patients.

Reliable, and easy to measure, immunological markers able to denote disease characteristics in multiple sclerosis (MS) patients are still lacking. We applied a multivariate statistical analysis on results obtained by measuring-by real-time RT-PCR-mRNA levels of 25 immunological relevant molecules in PBMCs from 198 MS patients. The combined measurement of mRNA levels of IL-1beta, TNF-alpha, TGF-beta, CCL20 and CCR3 was able to distinguish MS patients from healthy individuals. CXCR5, CCL5, and CCR3 combined mRNA levels identify primary progressive MS patients while TNF-alpha, IL-10, CXCL10 and CCR3 differentiate relapsing MS patients. Our results indicate that multi-parametric analysis of mRNA levels of immunological relevant molecules in PBMCs may represent a successful strategy for the identification of putative peripheral markers of disease state and disease activity in MS patients.

Adult↗

PubMed2003

Conventional and magnetization transfer MRI predictors of clinical multiple sclerosis evolution: a medium-term follow-up study.

The correlation between conventional MRI lesion load accumulation and multiple sclerosis clinical evolution is only modest. The assessment of brain parenchymal volume and of its changes over time may provide adjunctive MRI markers reflecting the more disabling aspects of multiple sclerosis pathology. Magnetization transfer (MT) MRI is sensitive to 'occult' multiple sclerosis-related brain damage and might also contribute to overcome the clinical/MRI paradox. In this study, we assessed the value of conventional and MT MRI-derived metrics in predicting the medium-term clinical evolution of patients with different multiple sclerosis phenotypes. We studied 73 patients, with relapsing-remitting multiple sclerosis (n = 34), secondary progressive multiple sclerosis (n = 19) and clinically isolated syndromes suggestive of multiple sclerosis (n = 20), and 16 healthy subjects. Brain dual-echo, T1-weighted (only in patients) and MT MRI scans were obtained at baseline and after 12 months. T2-hyperintense and T1-hypointense lesion volumes, normalized brain volume and average lesion MT ratio (MTR) were measured. MTR histograms from the whole brain tissue were also obtained. Clinical multiple sclerosis evolution and neurological disability were re-assessed in all patients after a median follow-up of 4.5 years. A multivariate analysis was performed to establish which clinical and MRI-derived variables were significant predictors of neurological deterioration at the end of the study period. At the end of follow-up, 34 patients showed significant neurological deterioration. The final multivariable model included average brain MTR percentage change after one year [P = 0.02, odds ratio (OR) = 0.86] and baseline T2-hyperintense lesion volume (P = 0.04, OR=1.04) as independent predictors of medium-term disability accumulation (r2 = 0.23). In this cohort of patients, abnormal values of average brain MTR changes showed a relatively high specificity (76.9%) and positive predictive value (59.1%) for Expanded Disability Status Scale score deterioration in individual cases. In patients with multiple sclerosis, a comprehensive estimation of the short-term changes of both conventional and MT MRI-detectable lesion burden might provide useful prognostic information for the medium-term clinical disease evolution.

Adult↗

PubMedDate not supplied

Sensitivity-encoded diffusion tensor MR imaging of the cervical cord.

The aim of this study was to apply sensitivity-encoding (SENSE) echo-planar imaging (EPI) to diffusion tensor MR imaging of the cervical cord, an anatomic region where MR imaging is particularly challenging. This technique was implemented with a SENSE reduction factor of 2 and used for imaging a water phantom and five healthy volunteers. Off-resonance artifacts were notably reduced compared with those of full-FOV EPI sequences. This approach to diffusion tensor MR imaging of the cervical cord is promising for future, more extensive clinical applications.

Adult↗