Alfonso Di Costanzo

Distributed changes in default-mode resting-state connectivity in multiple sclerosis.

Background: The default-mode network (DMN) has been increasingly recognized as relevant to cognitive status. Objectives: To explore DMN changes in patients with relapsing–remitting (RR) multiple sclerosis (MS) and to relate these to the cognitive status. Methods: Eighteen cognitively impaired (CI) and eighteen cognitively preserved (CP) RRMS patients and eighteen healthy controls (HCs), matched for age, sex and education, underwent neuropsychological evaluation and anatomical and resting-state functional MRI (rs-fMRI). DMN functional connectivity was evaluated from rs-fMRI data via independent component analysis. T2 lesion load (LL) was computed by a semi-automatic method and global and local atrophy was estimated by SIENAX and SPM8 voxel-based morphometry analyses from 3D-T1 images. Results: When the whole group of RRMS patients was compared with HCs, DMN connectivity was significantly weaker in the anterior cingulate cortex, whereas it was significantly weaker in the core but stronger at the periphery of the posterior cingulate cortex. These findings were more evident in CP than CI patients. Observed DMN changes did not correlate with global atrophy or T2-LL, but were locally associated with regional grey matter loss. Conclusion: Relapsing–remitting multiple sclerosis patients show a consistent dysfunction of DMN at the level of the anterior node. DMN distribution changes in the posterior node may reflect a possible compensatory effect on cognitive performance.

Multiparametric 3T MR approach to the assessment of cerebral gliomas: tumor extent and malignancy.

IntroductionContrast-enhanced MR imaging is the method of choice for routine assessment of brain tumors, but it has limited sensitivity and specificity. We verified if the addition of metabolic, diffusion and hemodynamic information improved the definition of glioma extent and grade.MethodsThirty-one patients with cerebral gliomas (21 high- and 10 low-grade) underwent conventional MR imaging, proton MR spectroscopic imaging (1H-MRSI), diffusion weighted imaging (DWI) and perfusion weighted imaging (PWI) at 3 Tesla, before undergoing surgery and histological confirmation. Normalized metabolite signals, including choline (Cho), N-acetylaspartate (NAA), creatine and lactate/lipids, were obtained by 1H-MRSI; apparent diffusion coefficient (ADC) by DWI; and relative cerebral blood volume (rCBV) by PWI.ResultsPerienhancing areas with abnormal MR signal showed 3 multiparametric patterns: “tumor”, with abnormal Cho/NAA ratio, lower ADC and higher rCBV; “edema”, with normal Cho/NAA ratio, higher ADC and lower rCBV; and “tumor/edema”, with abnormal Cho/NAA ratio and intermediate ADC and rCBV. Perienhancing areas with normal MR signal showed 2 multiparametric patterns: “infiltrated”, with high Cho and/or abnormal Cho/NAA ratio; and “normal”, with normal spectra. Stepwise discriminant analysis showed that the better classification accuracy of perienhancing areas was achieved when regarding all MR variables, while 1H-MRSI variables and rCBV better differentiated high- from low-grade gliomas.ConclusionMultiparametric MR assessment of gliomas, based on 1H-MRSI, PWI and DWI, discriminates infiltrating tumor from surrounding vasogenic edema or normal tissues, and high- from low-grade gliomas. This approach may provide useful information for guiding stereotactic biopsies, surgical resection and radiation treatment.

Correlation between fatigue and brain atrophy and lesion load in multiple sclerosis patients independent of disability.

BACKGROUND Fatigue is a major problem in multiple sclerosis (MS), and its association with MRI features is debated. OBJECTIVE To study the correlation between fatigue and lesion load, white matter (WM), and grey matter (GM), in MS patients independent of disability. METHODS We studied 222 relapsing remitting MS patients with low disability (scores <or=2 at the Kurtzke Expanded Disability Status Scale). Lesion load, WM and GM were measured by fully automated, operator-independent, multi-parametric segmentation method. T1 and T2 lesion volume were also measured by a semi-automated method. Fatigue was assessed by the Fatigue Severity Scale (FSS), and patients divided in high-fatigue (FSS>or=5; n=197) and low-fatigue groups (FSS<or=4; n=25). RESULTS High-fatigue patients showed significantly higher abnormal white matter fraction (AWM-f), T1 and T2 lesion loads, and significant lower WM-f, and GM-f. Multivariate analysis showed that high FSS was significantly associated with lower WM-f, and GM-f. Females and highly educated patients were significantly less fatigued. CONCLUSION These results suggest that among MS patients with low disability those with high-fatigue show higher WM and GM atrophy and higher lesion load, and that female sex and higher levels of education may play a protective role towards fatigue. Furthermore, they suggest that in MS, independent of disability, WM and GM atrophy is a risk factor to have fatigue.

Proton MR spectroscopy of cerebral gliomas at 3 T: spatial heterogeneity, and tumour grade and extent

This study aimed to evaluate the usefulness of proton MR spectroscopic imaging (1H-MRSI) at 3 T in differentiating high- from low-grade gliomas, and tumour from necrosis, oedema or normal tissue. Forty-four patients with brain gliomas and four with meningiomas were retrospectively reviewed. The normalised metabolites choline (nCho), N-acetylaspartate (nNAA), creatine (nCr) and lactate/lipids (nLL), and the metabolite ratios Cho/NAA, NAA/Cr and Cho/Cr were calculated. Necrotic-appearing areas showed two spectroscopic patterns: “necrosis” with variable nCho and high nLL, and “cystic necrosis” with variable nLL or nonevident peaks. Peri-enhancing oedematous-appearing areas showed three spectroscopic patterns (“tumour” with abnormal Cho/NAA, “oedema” with normal Cho/NAA and “tumour/oedema” with normal nCho and abnormal Cho/NAA) in gliomas, and one (“oedema”) in meningiomas. Peri-enhancing or peri-tumour normal-appearing areas showed two patterns (“infiltrated” with abnormal nCho and/or Cho/NAA and “normal” with normal spectra) in gliomas and one (“normal”) in meningiomas. Discriminant analysis showed that classification accuracy between high- and low-grade glioma masses was better with normalised metabolites or all parameters together than metabolite ratios and that among peri-enhancing areas was much better with normalised metabolites. The analysis of spatial distribution of normalised metabolites by 3-T 1H-MRSI helps to discriminate among different tissues, offering information not available with conventional MRI.

Brain MRI features of congenital- and adult-form myotonic dystrophy type 1: case-control study

To compare and characterize the magnetic resonance imaging (MRI) of brain in the congenital and adult form of myotonic dystrophy type 1, we evaluated five patients with congenital dystrophy type 1, 10 age- and 10 disease duration-matched patients with adult-form dystrophy type 1 and 20 age-matched healthy volunteers. The ventricular enlargement was evaluated by the ventricular:brain ratio, the signal intensity of white matter posterosuperior to trigones by reference to standard images and the white matter lesions by a semiquantitative method. In the congenital dystrophy type 1, MRI was characterized by ventriculomegaly and moderate/severe hyperintensity of white matter posterosuperior to trigones, which showed no correlation with the age. MRI in the adult-form dystrophy type 1 was strictly related to disease duration and varied between normal findings, except for temporo-polar white matter lesions, in age-matched patients and ventriculomegaly with white matter hyperintensities in disease duration-matched patients. These results suggest that the origin of MRI abnormalities in myotonic dystrophy type 1 is mainly developmental for the congenital form and mainly degenerative for the adult form.

Pattern and significance of white matter abnormalities in myotonic dystrophy type 1: an MRI study.

We reviewed the brain MRI of 66 patients with the adult form of myotonic dystrophy type 1 (DM1) to evaluate the extent and significance of white matter involvement and to look for a pattern of MRI abnormalities suggestive of DM1. White matter lesions (WMLs) and large Virchow Robin spaces (VRSs) were rated by semiquantitative methods and the signal intensity of white matter superior and posterior to the trigones (WMPST) by reference to standard images. Disease duration was correlated positively with WML and negatively with VRS scores. Patients were divided into four groups according to increasing severity of WMPST involvement: group A with mild WMPST hyperintensity, group B with large VRSs and mild or moderate WMPST hyperintensity, group C with moderate WMPST hyperintensity or mild WMPST hyperintensity with small WMLs, group D with severe WMPST hyperintensity or moderate WMPST hyperintensity with small WMLs. Disease duration, muscular impairment, lobar WMLs and brain atrophy significantly increased from groups A and B (not significantly different) to C and from C to D, while convexity VRSs significantly decreased from group B to C and from C to D. Lobar white matter involvement in DM1 seems progressive during the disease and may be characterized initially by large VRSs or mild WMPST hyperintensity, then by small WMLs or moderate WMPST hyperintensity, and finally by more extensive and confluent WMLs or diffuse white matter hyperintensity and by brain atrophy.

Dilated Virchow-Robin Spaces in Myotonic Dystrophy: Frequency, Extent and Significance

To study the frequency, extent and significance of dilated Virchow-Robin spaces (VRSs) in dystrophia myotonica (DM), we evaluated the cranial magnetic resonance imaging (MRI) of 41 patients with the adult form of DM and 41 healthy controls. Dilated VRSs and white matter lesions (WMLs) were rated according to semiquantitative methods. Convexity VRSs were more frequent (68 vs. 34%; p < 0.01) and severer (median scores: 4 vs. 0; p < 0.01) in DM patients than in controls, while lenticulostriate VRSs did not show significant differences in frequency (83 vs. 70%; p > 0.05) and severity (median scores: 4 vs. 3; p > 0.05). WMLs were more frequent (66 vs. 22%; p < 0.01) and severer (median scores: 5 vs. 0; p < 0.01) in patients. Disease duration was negatively correlated with convexity VRSs and positively with lobar (centrum semiovale) WML scores. Dilated convexity VRSs might be one of the initial findings in cranial MRI of DM, preceding the appearance of lobar WMLs.

Effects of different types of physical activity on the cognitive functions and attention in older people: A randomized controlled study.

This study aimed to evaluate the effects of different types of exercise on cognition. Eighty participants, 32 males and 48 females, aged 66.96 ± 11.73, volunteered for this study. The participants were randomly divided into the four following groups: Resistance Group (RG; n=20), involved in high intensity strength training; Cardiovascular Group (CVG; n=20), involved in high intensity cardiovascular training; Postural Group (PG; n=20) involved in low intensity training, based on postural and balance exercises; and Control Group (CG; n=20). Exercises were performed over the course of 12 weeks. All participants were tested for their cognitive functions pre- and post-intervention using the following neurocognitive tests: the Attentive Matrices Test, Ravens Progressive Matrices, Stroop Color and Word Interference Test, Trail Making Test and Drawing Copy Test. Statistical analysis showed that the CVG group improved significantly in the Attentive Matrices Test and Ravens Progressive Matrices (both p=<0.05), whereas the RG group improved in Drawing Copy Test time (p=<0.05). These results confirm that different types of exercise interventions have unique effects on cognition. Cardiovascular training is effective in improving performance attentive and analytic tasks, whereas resistance training is effective in improving praxis. Further investigation is necessary to evaluate the combination of the two exercise types in order to ascertain if their respective effects can be summated when performed together.

Distinctive Pattern of Serum Elements During the Progression of Alzheimer’s Disease

Element profiling is an interesting approach for understanding neurodegenerative processes, considering that compelling evidences show that element toxicity might play a crucial role in the onset and progression of Alzheimer’s disease (AD). Aim of this study was to profile 22 serum elements in subjects with or at risk of AD. Thirtyfour patients with probable AD, 20 with mild cognitive impairment (MCI), 24 with subjective memory complaint (SMC) and 40 healthy subjects (HS) were included in the study. Manganese, iron, copper, zinc, selenium, thallium, antimony, mercury, vanadium and molybdenum changed significantly among the 4 groups. Several essential elements, such as manganese, selenium, zinc and iron tended to increase in SMC and then progressively to decrease in MCI and AD. Toxic elements show a variable behavior, since some elements tended to increase, while others tended to decrease in AD. A multivariate model, built using a panel of six essential elements (manganese, iron, copper, zinc, selenium and calcium) and their ratios, discriminated AD patients from HS with over 90% accuracy. These findings suggest that essential and toxic elements contribute to generate a distinctive signature during the progression of AD, and their monitoring in elderly might help to detect preclinical stages of AD.

Familial aggregation of white matter lesions in myotonic dystrophy type 1.

This study aimed to determine whether white matter lesions, previously described as a frequent feature in myotonic dystrophy type 1 (DM1), aggregate within DM1 families or are sporadic findings, and to explore the relationship between these lesions and clinical or genetic features. Brain MRI of 60 DM1 patients belonging to 22 families were evaluated and white matter lesions were rated according to a semiquantitative method. Presence and extent of lobar, temporal or periventricular lesions showed a significant association with the family history of lesions and the disease duration, and no association with the CTG repeat size. Furthermore, parent-offspring and sibling pairs showed a significant positive concordance for lesion severity. White matter lesions demonstrate familial aggregation in DM1 and no relationship with CTG repeat length. These findings suggest that other genetic causes and/or unknown environmental factors influence the occurrence and severity of lesions in patients carrying the DM1 genetic defect.