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Giancarlo Comi

Publications and source records attributed to Giancarlo Comi.

At least 37 records · Page 2Linked to original sources
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

Progressive gray matter damage in patients with relapsing-remitting multiple sclerosis: a longitudinal diffusion tensor magnetic resonance imaging study.

BACKGROUND: Diffusion tensor magnetic resonance imaging (DT MRI) has the potential to provide in vivo information about tissue microstructure. In multiple sclerosis (MS), DT MRI has disclosed the presence of occult structural damage in the normal-appearing brain tissues. OBJECTIVE: To investigate whether DT MRI is sensitive to longitudinal changes of brain damage that may occur beyond the resolution of T2-weighted images in patients with relapsing-remitting MS. DESIGN: Twenty-six untreated patients with relapsing-remitting MS were followed up for 18 months. Dual-echo, DT and postcontrast T1-weighted MRIs of the brain were obtained at baseline and then every 3 months. Mean diffusivity (D) histograms of normal-appearing gray (GM) and white matter were produced. Total T2-hyperintense and T1-hypointense lesion volumes; normalized whole brain tissue, GM, and white matter volumes; percentage brain volume change between the study entry and exit images; average lesion D; and fractional anisotropy were also calculated. RESULTS: During the study period, a significant decrease of normalized whole brain tissue, average lesion fractional anisotropy and normal-appearing GM D histogram peak height, and a significant increase of average normal-appearing GM D and T2-hyperintense lesion volumes were observed. Changes of normal-appearing GM diffusivity were independent of the concomitant changes of normalized whole brain tissue and GM volumes. CONCLUSIONS: The DT MRI findings show progressive microstructural changes in the normal-appearing GM of patients with untreated relapsing-remitting MS. Such changes do not reflect a concomitant development of brain atrophy and confirm the importance of GM pathology in MS.

Adult↗
PubMed2005

Diffusion-tensor magnetic resonance imaging detects normal-appearing white matter damage unrelated to short-term disease activity in patients at the earliest clinical stage of multiple sclerosis.

BACKGROUND: Diffusion-tensor (DT) magnetic resonance imaging (MRI) has the potential to elucidate some characteristics of tissue microstructure inaccessible to other MRI techniques. OBJECTIVE: To investigate whether normal-appearing brain tissue abnormalities occur in patients with multiple sclerosis at the earliest clinical stage and whether their severity is predictive of a short-term disease evolution by using DT MRI. DESIGN: Forty-five patients and 22 healthy control subjects were studied. All patients had had a clinically isolated syndrome within the 3 months preceding study enrollment and paraclinical evidence of disease dissemination in space. During a single session, dual-echo, pulsed-gradient spin-echo echo-planar, and postgadolinium T1-weighted images of the brain were obtained from each subject. In patients, dual-echo and enhanced images were obtained after 3 and 12 months, to detect MRI signs of disease dissemination in time. An on-study neurological examination was also conducted to ascertain the occurrence of clinical relapses. Mean diffusivity and fractional anisotropy maps were derived from DT images. Normal-appearing white matter (NAWM) and normal-appearing gray matter mean diffusivity and fractional anisotropy histograms were produced and analyzed. RESULTS: During the study period, 29 patients showed MRI evidence of disease dissemination in time. When compared with healthy controls, patients showed higher average NAWM mean diffusivity (P = .01), lower average NAWM mean diffusivity peak height (P < .001), and fractional anisotropy (P < .001). The DT MRI characteristics of patients did not differ between those with and those without disease dissemination in time at follow-up. CONCLUSIONS: In patients with multiple sclerosis at the earliest clinical stage, the severity of NAWM damage does not predict new lesion formation in the short term, suggesting that the "diffuse" component of tissue damage is, at least partially, independent of the "discrete," predominantly inflammatory aspects of the disease since its clinical onset.

Adult↗
PubMed2005

Axonal injury and overall tissue loss are not related in primary progressive multiple sclerosis.

BACKGROUND: There is an increasing body of evidence that magnetic resonance imaging-occult tissue damage is an important component of primary progressive multiple sclerosis (PPMS) pathology. Proton magnetic resonance spectroscopy (1H-MRS) can be used to measure in vivo whole-brain N-acetylaspartate (WBNAA) concentrations, the decrease of whose levels is considered a marker of neuronal-axonal injury. OBJECTIVES: To study WBNAA 1H-MRS as a tool to provide information about irreversible brain damage in PPMS and to investigate the relationship between WBNAA and other magnetic resonance imaging measures of MS disease burden, including brain atrophy. METHODS: The following magnetic resonance pulse sequences of the brain were obtained from 32 patients with PPMS and 16 age-matched healthy subjects: (1) dual-echo turbo spin-echo; (2) T1-weighted spin-echo; and (3) 1H-MRS to measure WBNAA concentration. Brain total lesion volumes were measured. Normalized brain volumes were calculated using a fully automated technique. Absolute WBNAA amounts were calculated using a phantom replacement method and were then corrected for individual subjects' brain size. RESULTS: Levels of WBNAA concentrations and normalized brain volumes were significantly lower in patients with PPMS (mean values, 10.2 mm and 1500.0 mL, respectively) than in healthy controls (mean values, 12.9 mm and 1585.2 mL). Both WBNAA concentrations and normalized brain volumes were included as independent factors in the final model of a multivariable analysis predicting the subjects' condition. No significant correlations were found between WBNAA values and normalized brain volumes, WBNAA and T2-weighted or T1-weighted lesion volumes. CONCLUSIONS: Axonal-neuronal damage in the brain of patients with PPMS seems to occur, at least partially, independently of the burden of magnetic resonance imaging-visible lesions. Whole-brain N-acetylaspartate values and normalized brain volumes were unrelated in this cohort, thereby suggesting that 1H-MRS and atrophy assessment may provide in vivo complementary information about the actual extent of brain damage in PPMS.

Adult↗
PubMed2005

Visual evoked potentials may be recorded simultaneously with fMRI scanning: A validation study.

Integrating electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data may help to optimize anatomical and temporal resolution in the investigation of cortical function. Successful removal of fMRI scanning artifacts from continuous EEG in simultaneous recordings has been reported. We assessed the feasibility of recording reliable visual evoked potentials (VEPs) during fMRI scanning using available artifact removing procedures. EEG during administration of visual stimuli was recorded using MRI-compatible 32-channel equipment in nine normal subjects (mean age, 23.9 +/- 2.5 years), with and without fMRI acquisition. fMRI scanning and cardioballistographic artifacts were removed after subtraction of averaged artifact waveforms. Consistency between VEPs waveforms and of P1 and N1 peak latencies and amplitudes in the two conditions was assessed. Good correlation was found between VEP waveforms (Pearson's correlation coefficient: r(P) between 0.76-0.94 across subjects; P < 0.0001) and between latency or amplitude of P1 and N1 peaks (latencies: r = 0.7, P < 0.035; amplitudes: r > 0.65, P < 0.05; Spearman rank correlation coefficient) in the two recording conditions. No significant differences were found between P1 and N1 parameters in the two conditions (Wilcoxon signed rank test). Consistent VEP waveforms, latencies, and amplitudes with and without fMRI scanning indicate that reliable VEPs may be obtained simultaneously with fMRI recording. This possibility might be helpful by shortening recording times and reducing variability from learning, habituation, and fatigue phenomena from separate recordings for the integration of event-related EEG and fMRI data.

Adult↗
PubMed2005

Interferon-gamma and interferon-beta affect endogenous catecholamines in human peripheral blood mononuclear cells: implications for multiple sclerosis.

Interferon (IFN)-gamma plays a pivotal role in the pathogenesis of multiple sclerosis (MS), while IFN-beta may be able to modify the clinical course of the disease, eventually also by counterbalancing IFN-gamma-mediated effects. Catecholamines (CA) exert important effects on the immune response, both as transmitters between the nervous and the immune system, as well as autocrine/paracrine mediators in immune cells, and several lines of evidence support their involvement in MS. In particular, dysregulated production of CA seems to occur in peripheral blood mononuclear cells (PBMCs) of MS patients. We assessed the effects of IFN-beta and IFN-gamma on endogenous CA in PBMCs. In cultured PBMCs stimulated with phytohaemagglutinin (PHA), IFN-beta increased CA production and induced CA release in the culture medium, while IFN-gamma decreased both CA production and the expression of mRNA for the CA-synthesizing enzyme tyrosine hydroxylase. Coincubation with both IFNs prevented the inhibitory effect of IFN-gamma, as well as the stimulatory effect of IFN-beta. IFNs are the first physiological compounds shown to affect endogenous CA in PBMCs: in view of the role of CA-dependent mechanisms in the immune response, these findings may help to better understand the mechanisms of action of IFN-beta as an immunomodulatory drug in MS.

Blotting, Northern↗
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↗
PubMed2005

Schwann cell overexpression of the GPR7 receptor in inflammatory and painful neuropathies.

The human 7-transmembrane receptor GPR7 has sequence similarity to opioid and somatostatin receptors, and can be activated by the recently discovered neuropeptides NPB and NPW. This receptor is highly expressed in the nervous system, with suggested roles in neuroendocrine events and pain signaling. In this study, we investigated whether the GPR7 receptor is expressed in the peripheral nervous system under normal and pathological conditions. A low level of GPR7 receptor was observed in myelin-forming Schwann cells in both normal human and rat nerve, and in primary rat Schwann cell cultures. Peripheral nerve samples taken from patients exhibiting inflammatory/immune-mediated neuropathies showed a dramatic increase of GPR7 receptor expression restricted to myelin-forming Schwann cells. Complementary animal models of immune-inflammatory and ligation-induced nerve injury and neuropathic pain similarly exhibited an increased myelin-associated expression of GPR7 receptor. These results suggest a relationship between the pathogenesis of inflammatory/immune-mediated neuropathies, GPR7 receptor expression, and pain transmission.

Adult↗
PubMed2005

Cortical adaptation in patients with MS: a cross-sectional functional MRI study of disease phenotypes.

BACKGROUND: Movement-associated cortical reorganisation is known to occur in multiple sclerosis (MS). We aimed to define the development of such cortical reorganisation by comparing data from patients with different disease phenotypes. METHODS: We studied patients with different phenotypes of MS: 16 patients with a clinically isolated syndrome (CIS), 14 patients with relapsing-remitting MS (RRMS) and no disability, 15 patients with RRMS and mild clinical disability, and 12 patients with secondary progressive MS (SPMS). Patients did a simple motor task with their unimpaired dominant hand during MRI, which was compared across the phenotype groups. FINDINGS: Patients with a CIS activated more of the contralateral primary sensorimotor cortex than those with RRMS and no disability, whereas patients with RRMS and no disability activated more of the supplementary motor area than those with a CIS. Patients with RRMS and no disability activated more of the primary sensorimotor cortex, bilaterally, and more of the ipsilateral supplementary motor area than patients with RRMS and mild clinical disability. Conversely, patients with RRMS and mild clinical disability activated more of the contralateral secondary somatosensory cortex and inferior frontal gyrus, and the ipsilateral precuneus. Patients with RRMS and mild clinical disability activated more of the contralateral thalamus and of the ipsilateral secondary somatosensory cortex than those with SPMS. However, patients with SPMS activated more of the inferior frontal gyrus, bilaterally, the middle frontal gyrus, bilaterally, the contralateral precuneus, and the ipsilateral cingulate motor area and inferior parietal lobule. INTERPRETATION: Movement-associated cortical reorganisation in patients with MS seems to vary across individuals at different stages of disease. Our study suggests that early in the disease course more areas typically devoted to motor tasks are recruited. Then bilateral activation of these regions is seen, and late in the disease course, areas that healthy people recruit to do novel or complex tasks are activated.

Adaptation, Physiological↗
PubMed2005

Clinical trials in multiple sclerosis: methodological issues.

PURPOSE OF REVIEW: The availability of partially effective immunomodulatory and immunosuppressive treatments for relapsing multiple sclerosis (MS) opens important ethical, methodological and practical issues in the design and conduct of new clinical trials in these patients. RECENT FINDINGS: The recommendation of the National Health Authorities to prioritize phase III clinical trials using placebo arm raises ethical questions. In addition, patients are reluctant to be involved in such trials. Alternative clinical trial designs will be discussed. Relapses and active lesions are accepted measures of disease activity; new/enlarging T2 lesions and/or enhancing lesions are accepted surrogate markers of disease activity in phase II clinical trials. On the contrary, there are no accepted magnetic resonance imaging (MRI) surrogate markers of disease progression and also the clinical measures to monitor the degenerative aspects of the disease are not without important limitations. New scales of impairment, disability and quality of life will be reviewed extensively. We will also focus on the value of modern and quantitative MRI techniques, which hold substantial promise as tools to estimate the extent of MS-related irreversible tissue loss. SUMMARY: The use of an active comparator in a superior clinical-trial design is becoming an attractive option for testing the efficacy of new drugs in relapsing MS. At present there are no fully reliable and sensitive clinical markers of the accumulation of irreversible tissue damage in MS. Although additional extensive application in longitudinal studies is needed, modern MRI techniques are promising tools to monitor the neurodegenerative aspects of MS.

Animals↗
PubMed2005

Autologous stem cell transplantation as rescue therapy in malignant forms of multiple sclerosis.

Malignant forms of multiple sclerosis (MS) represent a limited group of very aggressive demyelinating diseases, which rapidly progress to severe disability leading often to life-threatening conditions. On these clinical entities, currently available therapies for MS are not very effective. Recently, it has been demonstrated that intense immunosuppression followed by autologous stem cell transplantation (ASCT) can affect the clinical course of individuals with severe MS and completely abrogate the inflammatory activity detected by magnetic resonance imaging (MRI). We report on the treatment with intense immune ablation followed by ASCT of three patients with malignant MS whose clinical course indicated a dramatically poor prognosis. This procedure succeeded in halting the rapidly worsening course of disease. The effect was long lasting, as demonstrated by a sustained efficacy over a two-year period in two subjects and 12 months in the third case. In addition, a striking effect on inflammation-related MRI findings was obtained. These results support a role for intense immunosuppression followed by ASCT as treatment in rapidly evolving malignant MS cases unresponsive to conventional therapies.

Adolescent↗
PubMed2005

Regional brain atrophy evolves differently in patients with multiple sclerosis according to clinical phenotype.

BACKGROUND AND PURPOSE: Progressive brain atrophy is a well-known feature of multiple sclerosis (MS). We characterized the spatial evolution of atrophy in different MS phenotypes. METHODS: Dual-echo and T1-weighted MR images were obtained in 70 patients with MS and 10 healthy control subjects at entry and after 15 months. Within-group changes in regional atrophy were assessed by applying Structural Image Evaluation Using Normalization of Atrophy software and statistical parametric mapping analysis. Reported differences are for P <.001. RESULTS: During follow-up, patients with relapsing-remitting MS (RRMS) differences significant atrophy around the ventricular system; pericerebellar spaces; cerebellar tentorium; putamen; corpus callosum; cingulate sulcus; hippocampus; parieto-occipital fissure; lateral fissure; and frontal, parietal, temporal, and occipital cortex. Patients with secondary progressive MS developed significant atrophy of the cingulate sulcus; pulvinar; caudate nucleus; anterior orbital gyrus; mammillary body; fourth ventricle; and regions of frontal, parietal, temporal, and occipital cortex. Patients with primary progressive MS developed significant atrophy of the bilateral central sulcus; caudate nucleus; prepontine and quadrigeminal cisterns; lateral ventricle; and regions of frontal, parietal, temporal, and occipital cortex. In all phenotypes, the development of atrophy in some regions was significantly correlated with the accumulation of T2- and T1-visible lesions and clinical disability (r = -0.57 to -0.86). CONCLUSION: In MS, brain atrophy develops involving different structures in the different phenotypes. While ventricular enlargement is predominant in RRMS, cortical atrophy seems to be more important in the progressive forms. Measures of regional brain atrophy were significantly correlated with disability, suggesting that this approach is promising for bridging the gap between clinical and MR imaging findings in MS.

Adult↗
PubMed2005

Persistence of congenital mirror movements after hemiplegic stroke.

We describe a case of hereditary congenital mirror movements (MMs) in a 76-year-old man, who after an ischemic stroke, had persistence of MMs in the paretic hand during voluntary movements of the contralateral arm. By using functional MR imaging to investigate the performance of motor and sensory tasks with the affected and the unaffected hands, we found evidence for increased ipsilateral primary motor cortex activity and reduced transcallosal inhibition. Both these mechanisms are likely to be involved in the genesis of MMs.

Aged↗
PubMed2005

A widespread pattern of cortical activations in patients at presentation with clinically isolated symptoms is associated with evolution to definite multiple sclerosis.

BACKGROUND AND PURPOSE: Movement-associated cortical changes have been detected at the earlier clinical stage multiple sclerosis. Our purpose was to assess whether different patterns of cortical recruitment are associated with the short-term evolution of definite multiple sclerosis (MS). METHODS: We followed for 1 year a group of patients with clinically isolated syndromes (CISs) suggestive of MS and compared the baseline movement-associated patterns of cortical activations between those patients with and those without evolution to definite MS. RESULTS: Those patients in whom MS did not evolve had more significant activations of several areas part of the "classic" motor network; those who went on to develop MS had more significant activations of several regions in the frontal, parietal, temporal, and occipital lobes. CONCLUSION: In CIS patients, the extent of early cortical reorganization following tissue injury might be a factor associated with a different disease evolution.

Adult↗
PubMed2004

Short-term accrual of gray matter pathology in patients with progressive multiple sclerosis: an in vivo study using diffusion tensor MRI.

The mechanisms underlying the progressive course of multiple sclerosis (MS) are not fully understood yet. Since diffusion tensor (DT) MRI can provide quantitative estimates of both MRI-visible and MRI-occult brain damage related to MS, the present study investigated the value of DT MRI-derived measures for the assessment of the short-term accumulation of white and gray matter (GM) pathology in patients with primary progressive (PP) and secondary progressive (SP) MS. Fifty-four patients with PPMS and 22 with SPMS were studied at baseline and after a mean follow-up of 15 months. Dual-echo, T1-weighted, and DT MRI scans of the brain were acquired on both occasions. Total lesion volumes (TLV) and percentage brain volume changes (PBVC) were computed. Mean diffusivity (MD) and fractional anisotropy (FA) maps of the normal-appearing white (NAWM) and gray matter (NAGM) were produced, and histogram analysis was performed. In both patient groups, a significant increase of average lesion MD (P = 0.01) and of average NAGM MD (P = 0.007) was found at follow-up. No significant differences between PPMS and SPMS patient groups were found for the on-study changes of any MRI-derived measure. No significant correlations were found between the percentage changes of DT MRI-derived measures and those of TLV and PBVC. No significant changes of DT MRI-derived measures were observed in age-matched healthy controls over the same study period. Over a 1-year period of follow-up, DT MRI can detect tissue changes beyond the resolution of conventional MRI in the NAGM of patients with progressive MS. The accumulation of DT MRI-detectable gray matter damage does not seem to merely depend upon the concomitant increase of T2-visible lesion load and the reduction of brain volume. These observations suggest that progressive NAGM damage might yet be an additional factor leading to the accumulation of disability in progressive MS.

Adult↗
PubMed2004

A preliminary diffusion tensor and magnetization transfer magnetic resonance imaging study of early-onset multiple sclerosis.

BACKGROUND: Early-onset multiple sclerosis (MS) typically has a more favorable course than adult-onset disease. OBJECTIVE: To assess the extent of microscopic tissue damage in the brain and cervical cord of patients with early-onset MS. DESIGN: During a single magnetic resonance imaging session, images of the brain and spinal cord were obtained using diffusion tensor and magnetization transfer magnetic resonance imaging. PATIENTS: We studied 13 patients with early-onset MS and 10 healthy volunteers. RESULTS: Compared with control subjects, patients with early-onset MS showed only a slight increase of the average mean diffusivity of the normal-appearing brain tissue. CONCLUSION: The relatively modest central nervous system damage detected in these patients might explain why early-onset MS typically has a more favorable clinical course than adult-onset MS.

Adolescent↗
PubMed2004

European study on intravenous immunoglobulin in multiple sclerosis: results of magnetization transfer magnetic resonance imaging analysis.

BACKGROUND: Magnetization transfer magnetic resonance imaging (MT MRI) can provide in vivo markers reflecting the severity of multiple sclerosis-related brain damage occurring within and outside T2-visible lesions. OBJECTIVE: To investigate the effect of intravenous immunoglobulin (IVIG) treatment on the accumulation of brain damage in patients with secondary progressive multiple sclerosis (SPMS), measured using MT MRI.Design, Patients, and Intervention Seventy patients with SPMS participating in the European, multicenter, randomized, double-blind, placebo-controlled trial of IVIG in SPMS underwent brain T2-weighted and MT MRI at baseline and after 12 and 24 months. The MT MRI scans were post-processed and analyzed to obtain MT ratio values from T2-visible lesions and MT ratio histograms from the normal-appearing brain tissue (NABT). RESULTS: At baseline, a significant difference was found for NABT MT ratio histogram peak height (P =.003) between treated patients and patients receiving placebo. No significant differences between treated patients and those receiving placebo were found for any of the considered MT MRI-derived metrics in terms of treatment x time interaction. Nevertheless, over the 24-month period, the placebo patients experienced a 6.75% reduction of the NABT MT ratio histogram peak height, whereas treated patients experienced only a 0.92% reduction of the NABT MT ratio histogram peak height. CONCLUSIONS: This study did not show any statistically significant effect of IVIG on MT MRI quantities. Nevertheless, the markedly different percentage change of the NABT MT ratio histogram peak height over time between patients receiving placebo and treated patients suggests a possible role of IVIG treatment in preventing the loss of "truly" normal brain tissue in SPMS patients.

Brain↗