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G Comi

Publications and source records attributed to G Comi.

At least 163 records · Page 9Linked to original sources
PubMed2000

Neurophysiological investigations in multiple sclerosis.

The advent of magnetic resonance imaging techniques has greatly reduced the diagnostic value of neurophysiological tests, particularly evoked potentials, in multiple sclerosis patients, because of the higher sensitivity in revealing subclinical involvement of the central nervous system. Technical progress and new methods of investigating afferent and efferent nervous pathways would seem to increase the sensitivity in detecting neural dysfunction, but the 'clinical gain' is modest at best. More promising is the utilization of neurophysiological tests to quantify the severity of white matter involvement. Transversal and longitudinal studies have demonstrated good correlations between neurophysiological parameters and disability measures, indicating that a battery of neurophysiological tests could be useful in monitoring the disease evolution in single patients and as surrogate endpoints in clinical trials. Further studies are needed for a better definition of the applications of evoked potentials and other neurophysiological techniques. Finally, event-related potentials and advanced electroencephalogram techniques, such as coherence analysis, could provide useful information on the pathophysiology of cognitive dysfunction, so common in multiple sclerosis patients, and with a strong impact on the quality of life.

Electroencephalography↗
PubMed2000

Changes in the normal appearing brain tissue and cognitive impairment in multiple sclerosis.

OBJECTIVES: To assess (a) whether the changes in the normal appearing brain tissue (NABT), as revealed by magnetisation transfer (MT) histogram analysis, correlates with cognitive dysfunction in patients with multiple sclerosis and (b) the relative contribution of these changes by comparison with that of multiple sclerosis lesions visible on conventional MRI. METHODS: Dual echo, T1 weighted and MT scans of the brain were obtained in 12 patients with multiple sclerosis with cognitive impairment and in seven without cognitive impairment. Lesion loads were assessed from T2 and T1 weighted scans. To create MT histograms of the NABT, multiple sclerosis lesion outlines from dual echo scans were superimposed automatically and nulled out from the coregistered and scalp stripped MTR maps. Average lesion MT ratio (MTR) and brain size were also measured. RESULTS: T2 and T1 lesion loads were significantly higher and the average lesion MTR and brain size were significantly lower in the group of cognitively impaired patients. Patients with cognitive deficits also had significantly lower average MTR and peak location of the NABT histogram. Logistic regression analysis showed that 68% of the total variance was explained by average NABT-MTR alone. A multivariable regression model showed that NABT-MTR was the only factor that significantly correlated with cognitive impairment in these patients (p=0.001). CONCLUSIONS: The extent of abnormalities which go undetected when using conventional MRI is relevant in determining cognitive impairment in multiple sclerosis.

Adult↗
PubMed2000

Brain involvement in systemic immune mediated diseases: magnetic resonance and magnetisation transfer imaging study.

OBJECTIVE: Magnetisation transfer imaging (MTI) provides information about brain damage with increased pathological specificity over conventional MRI and detects subtle abnormalities in the normal appearing brain tissue, which go undetected with conventional scanning. Brain MRI and MTI findings were compared in patients with multiple sclerosis (MS) and systemic immune mediated diseases (SIDs) affecting the CNS to investigate their roles in understanding the nature of brain damage in these diseases. METHODS: Brain dual echo, T1 weighted and MTI scans were obtained in patients affected by systemic lupus erithematosus (SLE) with (NSLE, n=9) and without clinical CNS involvement (n=15), Behçet's disease (BD) (n=5), Wegener's granulomatosis (WG) (n=9), and antiphospholipid antibody syndrome (APLAS) (n=6). Ten patients with clinically definite MS and 15 healthy controls also underwent the same scanning protocol. Brain MRI and MT ratio (MTR) images of the same subject were coregistered and postprocessed to obtain MTR histograms of the whole brain and of the NABT. RESULTS: Brain hyperintense lesions were found in all patients with MS and with NSLE and in 5/15 patients with SLE, 5/9 with WG, 1/5 with BD, and 3/6 with APLAS. The lesion burden in the brain was significantly higher in patients with MS compared with all the other disease groups. All MTR histogram parameters were significantly different among patient subgroups. Patients with MS had significantly lower average MTR than all except patients with NSLE and significantly lower peak height and location than patients with SLE. patients with NSLE had significantly lower average MTR than patients with SLE. CONCLUSIONS: Microscopic brain tissue damage is relevant in patients with MS, but, apart from patients with NSLE, it seems to be absent in systemic immune mediated diseases, even in the presence of macroscopic MRI lesions or clinical evidence of CNS involvement.

Adult↗
PubMed2000

Electroencephalographic coherence analysis in multiple sclerosis: correlation with clinical, neuropsychological, and MRI findings.

OBJECTIVE: To explore functional corticocortical connections in multiple sclerosis by means of coherence of the EEG, and to evaluate their correlations with the degree of cognitive impairment and with brain lesion load assessed by MRI. METHODS: EEG coherence was studied from 28 patients with clinically definite multiple sclerosis. Ten minutes of resting EEG were recorded with 20 scalp electrodes, with binaural reference. FFT power and coherence were calculated in artifact free epochs of 1 second and compared with values from 22 control subjects of comparable age and sex distribution. Patients also underwent MRI (n=27) and neuropsychological examination (n=21). RESULTS: Compared with controls, patients with multiple sclerosis showed increased theta power in the frontotemporal-central regions (p<0.005). theta Band coherence was decreased between homologous areas (p<0.02). alpha Band coherence was decreased both in the local and long distance connections (p<0.0005). These findings were most striking both in patients with high MRI subcortical lesion load and in patients with cognitive involvement. A significant correlation was found between interhemispheric theta (p=0.02) and alpha (p=0. 017) and anteroposterior alpha (p=0.013) coherence and subcortical MRI lesion load, but not with exclusively periventricular lesion load. CONCLUSIONS: These findings support the hypothesis that cognitive impairment in multiple sclerosis is mostly dependent on involvement of corticocortical connections related to demyelination and/or axonal loss within the white matter immediately underlying the cortex.

Adult↗
PubMed2000

Relative contributions of brain and cervical cord pathology to multiple sclerosis disability: a study with magnetisation transfer ratio histogram analysis.

OBJECTIVE: To assess (a) the correlations between magnetisation transfer ratio (MTR) histogram derived measures of the brain and the cervical cord from patients with different multiple sclerosis phenotypes and (b) the correlation between these metrics and clinical disability. Magnetisation transfer imaging is sensitive to the most destructive aspects of multiple sclerosis pathology. Magnetisation transfer ratio histogram analysis encompasses the macroscopic and the microscopic lesion burdens. METHODS: Seventy seven patients with multiple sclerosis were studied (40 relapsing-remitting (RR), 28 secondary progressive (SP), and nine primary progressive (PP)). For the brain, we obtained dual echo, T1 weighted, and gradient echo (GE) scans (with and without an MT saturation pulse). For the cervical cord, fast short tau inversion recovery (STIR) and GE scans (with and without an MT saturation pulse) were obtained. Brain T2 and T1 weighted lesion volumes (LVs) were measured. The number and length of cord lesions on fast STIR scans were assessed. Magnetisation transfer ratio maps were created from GE images and MTR histograms of the entire brain and cervical cord were obtained. RESULTS: Brain T1 LV, and number and size of cord lesions were significantly higher and brain MTR histogram peak location was significantly lower in patients with SPMS than those with RRMS or PPMS. Cord MTR histogram peak location was also significantly lower in patients with SPMS than in those with RRMS. The univariate correlations between MTR histogram derived metrics obtained from the brain and the cervical cord were all non-significant, with the exception of that between average brain MTR and cord MTR histogram peak location. On a multivariable analysis, both increasing brain T2 LV and decreasing cord MTR histogram peak location values were significantly associated with a higher probability for patients to have SPMS or to have locomotor disability. CONCLUSIONS: This study shows that the extent and severity of tissue damage in the brain and cervical cord are both relevant to determine disability in multiple sclerosis and that the assessment of brain and cord pathology provides complementary information.

Adult↗
PubMed2000

Temperature gradient gel electrophoresis of the amplified product of a small 16S rRNA gene fragment for the identification of Listeria species isolated from food.

The development of a rapid method for the identification of Listeria spp. is described. It is based on the polymerase chain reaction amplification of a small fragment from the 16S rRNA gene followed by temperature gradient gel electrophoresis. Forty-five strains of Listeria spp. (Listeria monocytogenes, Listeria innocua, Listeria ivanovii, Listeria seeligeri, and Listeria welshimeri) were used for the optimization of the protocol. No differences were observed between the results of the identification of the strains tested using traditional methods and those obtained by polymerase chain reaction-temperature gradient gel electrophoresis analysis.

Electrophoresis, Polyacrylamide Gel↗
PubMed2000

Cortical/subcortical disease burden and cognitive impairment in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: We assessed whether the extent of macro- and microscopic disease in the cortical and subcortical brain tissue, as revealed by MR and magnetization transfer (MT) imaging, correlates with cognitive dysfunction in patients with multiple sclerosis (MS). METHODS: Dual-echo rapid acquisition with relaxation enhancement (RARE), fast fluid-attenuated inversion recovery (fast-FLAIR), T1-weighted, and MT MR images of the brain were obtained from 16 MS patients with cognitive impairment and from six without. Impaired and unimpaired patients were similar across demographic and other disease-related variables. Total and cortical/subcortical lesion loads were assessed using RARE, fast-FLAIR, and T1-weighted sequences. In each patient, cortical/subcortical disease was also assessed by means of MT ratio (MTR) histographic analysis. RESULTS: All the impaired patients had multiple hyperintense lesions in the cortical/subcortical regions on both RARE and fast-FLAIR images; two unimpaired patients had such lesions on the RARE images and four had them on the fast-FLAIR images. Total and cortical/subcortical RARE/fast-FLAIR hyperintense and T1 hypointense lesion loads were significantly greater in the group of cognitively impaired patients. Patients with cognitive deficits also had significantly lower MTR histographic values for all the variables. A multivariate regression model showed that average cortical/subcortical brain MTR was the only factor that was significantly associated with cognitive impairment. CONCLUSION: The extent and severity of MS disease in the cortical and subcortical regions significantly influence the cognitive functions of MS patients. MTR histographic findings suggest that subtle changes undetectable by conventional imaging are also important in determining MS cognitive decline.

Adult↗
PubMed2000

Event-related brain potentials: laplacian transformation for multichannel time-frequency analysis.

During a visual-motor task the movement strategies and the learning processes are investigated. A group of 10 normal young volunteers underwent the experiment. The EEG signal was recorded through the 10-20 acquisition system during the execution of a task after a visual input. Each subject repeated the movement several times in three different conditions: i) without knowledge of the performance; ii) with visual feedback; iii) with knowledge of the result. The signal was transformed through Laplacian operator in order to eliminate the spurious coherence and then time-variant coherence was calculated. Different trends of the coherence function have been evidenced in subjects learning and not learning the better movement strategy. In particular, relations have been found between frontal, central and occipital electrodes in medium and high frequency ranges.

Adult↗
PubMed1999

Correlations between clinical and MRI involvement in multiple sclerosis: assessment using T(1), T(2) and MT histograms.

The degree of disability and cerebellar and brainstem impairments in multiple sclerosis (MS) patients were correlated with several magnetic resonance imaging (MRI) measures of tissue damage in the whole brain, cerebellum and brainstem to determine the relative contributions of the factors underlying the development of disability in MS. Dual-echo conventional spin-echo, T(1)-weighted and magnetization transfer (MT) scans were obtained from 72 patients with MS and 20 age- and sex-matched controls. The following MRI-derived quantities were considered for the brain as a whole, for the cerebellum and for the brainstem: (a) the number and volume of lesions seen on T(2)-weighted images; (b) the number and volume of lesions seen on T(1)-weighted images; (c) the size of these structures measured on T(1)-weighted scans; (d) the average MT ratio (MTR), peak height and peak position for the MT histogram. With univariate analysis, many MRI measures were significantly different in patients with different levels of disability or cerebellar and brainstem functional system impairments. However, with multivariate analysis, only whole-brain average MTR was significantly related to physical disability, while cerebellar and brainstem T(1) lesion volume and average MTR were related to cerebellar and brainstem impairment. This study shows that increased pathological damage in clinically eloquent sites is the major cause of disability in patients with MS. It also suggests that measures derived from MT histogram analysis and T(1) hypointense lesion load should be considered when evaluating long-term MS evolution.

Adult↗
PubMed1999

Cumulative effect of a weekly low dose of interferon beta 1a on standard and triple dose contrast-enhanced MRI from multiple sclerosis patients.

In patients with multiple sclerosis (MS), we assessed the short- and long-term effects of a weekly low dose of recombinant human interferon beta 1a (rh-IFN beta 1a) on the development of new magnetic resonance imaging (MRI) lesions enhancing at different gadolinium-DTPA (Gd) doses. Every 4 weeks, standard dose (SD) (0.1 mmol/kg of Gd) and triple dose (TD) (0.3 mmol/kg of Gd) Gd-enhanced brain MRI scans were obtained from 18 patients with relapsing-remitting MS for 3 months before treatment, 4 months after treatment initiation (treatment period [TP] I) and 4 months after 1 year of treatment (TP II) with 44 microg of rh-IFN beta 1a subcutaneously, once a week. The mean numbers of new enhancing lesions/patient/month were 1.4 (baseline), 1.1 (TP I) and 0.7 (TP II) on SD scans and 2.4 (baseline), 1.3 (TP I) and 0.8 (TP II) on TD scans. On average, treatment decreased the rate of new enhancing lesion appearance by 24% (SD scans) and 45% (TD scans) during TP I and by 52% (SD scans) and 66% (TD scans) during TP II. This study indicates that the effect of 44 microg of rh-IFN beta 1a given once a week on MRI-monitored MS activity increases over time. It also suggests that TD MRI is useful in detecting early treatment effect, that would otherwise be missed.

Adjuvants, Immunologic↗
PubMed1999

A multiparametric MRI study of frontal lobe dementia in multiple sclerosis.

Previous studies achieved conflicting results when correlating magnetic resonance imaging (MRI) abnormalities and cognitive impairment in multiple sclerosis (MS) patients. Recently, the estimation of MS lesion load on T1-weighted images and the analysis of magnetization transfer ratio (MTR) histograms, increased the degree of the correlation between physical disability and MRI findings in MS. We assessed the relationship of conventional and non-conventional MRI-derived measures with frontal lobe dementia in MS. Dual echo, T1-weighted and MT MRI scans of the brain were obtained in 11 MS patients with and in 11 without frontal lobe dementia, matched for age, sex, education and disability. Total (TLL) and frontal (FLL) lesion loads were assessed from T2- and T1-weighted scans. MTR histogram analysis was performed for the whole brain, the frontal lobe and the cerebellum. Median TLL and FLL were significantly higher in cognitively impaired patients on both T2- and T1-weighted scans. The MRI measure that better discriminated the two groups of patients was T1-weighted TLL (median values were 19.1 ml for demented and 1.9 ml for non-demented patients, P=0.006). Average MTR, peak height and location of overall brain and frontal lobe histograms were significantly lower for cognitively impaired than for cognitively intact patients (P values ranged from 0.0001 to 0.001). Cerebellar MTR histogram metrics did not significantly differ in patients with and without cognitive decline. The presence of cognitive decline in MS is associated with the extent and pathological severity of brain MRI abnormalities.

Dementia↗
PubMed1999

Quantitative brain volumetric analysis from patients with multiple sclerosis: a follow-up study.

Using magnetic resonance imaging (MRI), we measured in patients with multiple sclerosis (MS) the brain volume changes over a one year period and correlated them with changes in disability. Three-dimensional T1-weighted magnetization prepared rapid acquisition gradient-echo (MP-RAGE) (with subsequent reconstruction of 1-mm thick axial slices) scans of the brain were obtained at baseline and after one year from 14 MS patients. The average percentage decrease of total brain volume was ten times higher for patients who had a deterioration in their expanded disability status scale (EDSS) scores than for those who had not (mean percentage changes were -4.7 and -0.4%, respectively). Over a short time follow-up period, the decrease of brain volume was higher in the MS patients with clinical evolution compared to those with unchanged disability.

Brain↗
PubMed1999

Focal cognitive impairment in mitochondrial encephalomyopathies: a neuropsychological and neuroimaging study.

Mitochondrial encephalomyopathies (ME) are a multisystemic group of diseases characterized by a wide range of biochemical and genetic mitochondrial defects with a variable mode of inheritance. We studied the neuropsychological profile, magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) data in a group of ME patients in order to look for common or specific cognitive defects and a possible correlation with related brain areas. Three main cognitive areas were assessed: general intelligence, memory functions and visuo-perceptual skills. Our sample included 16 ME patients (nine males, seven females) aged 25-68 years (mean age 45.2, SD 13.0). No sign of mental deterioration was found in the group of elderly subjects. Despite subjects showing no global cognitive impairment they scored lower in nonverbal versus verbal tasks. Visuo-spatial skills and short-term memory were selectively impaired. There was no correlation between neuropsychological results and age, illness duration, age of onset, clinical phenotypes, genetic mitochondrial alterations and pharmacological therapy. The most frequent SPECT pattern observed was the hypoperfusion of temporal lobes, with a direct localization in the temporal cortex and with prevalent mesial involvement. The neuropsychological profile and SPECT imaging revealed similarities with focal defects.

Adult↗
PubMed1999

MRI and magnetization transfer imaging changes in the brain and cervical cord of patients with Devic's neuromyelitis optica.

OBJECTIVES: To assess MRI and magnetization transfer (MT) imaging changes in the brain and cervical cord from patients with Devic's neuromyelitis optica (DNO), and to compare them with those from patients with MS. BACKGROUND: In MS, MT imaging detects changes within the normal-appearing brain tissue (NABT). MS lesions in the cord usually are isointense on T1-weighted images. No study has investigated these two aspects in patients with DNO. METHODS: The authors obtained dual echo, fast fluid-attenuated inversion recovery, T1-weighted, and MT scans of the brain from 8 DNO patients, 10 MS patients, and 9 healthy volunteers. T2-weighted, short-tau inversion recovery, T1-weighted, and MT scans of the cervical cord also were obtained. The authors identified lesions visible on the different scans and quantified the volumes for those in the brain. MT ratio (MTR) histogram analysis of the NABT and of the entire cervical cord also was performed. RESULTS: No brain abnormalities were found on the T2-weighted scans from healthy volunteers and from seven DNO patients. No significant difference was found for any of the NABT-MTR histogram metrics between DNO patients and controls, whereas MS patients had a significantly lower histogram average MTR and peak height. No abnormalities were seen on any of the scans of the cervical cord from healthy volunteers. All DNO patients had a single lesion longer than two vertebral segments. Five of them were hypointense on T1-weighted scans. The authors identified 24 cord lesions from MS patients: 22 were shorter than two vertebral segments and none was hypointense. There was no difference in cervical cord MTR histogram metrics between DNO and MS patients. CONCLUSIONS: This study demonstrates that patients with Devic's neuromyelitis optica (DNO) and MS have different imaging characteristics of the brain and cervical cord. This provides further evidence that DNO is a clinical entity separate from MS.

Adult↗
PubMed1999

Caspase-1 regulates the inflammatory process leading to autoimmune demyelination.

T cell-mediated inflammation is considered to play a key role in the pathogenic mechanisms sustaining multiple sclerosis (MS). Caspase-1, formerly designated IL-1beta-converting enzyme, is crucially involved in immune-mediated inflammation because of its pivotal role in regulating the cellular export of IL-1beta and IL-18. We studied the role of caspase-1 in experimental autoimmune encephalomyelitis (EAE), the animal model for MS. Caspase-1 is transcriptionally induced during EAE, and its levels correlate with the clinical course and transcription rate of proinflammatory cytokines such as TNF-alpha, IL-1beta, IFN-gamma, and IL-6. A reduction of EAE incidence and severity is observed in caspase-1-deficient mice, depending on the immunogenicity and on the amount of the encephalitogenic myelin oligodendrocyte glycoprotein (MOG) peptide used. In caspase-1-deficient mice, reduced EAE incidence correlates with defective development of anti-MOG IFN-gamma-producing Th1 cells. Finally, pharmacological blockade of caspase-1 in Biozzi AB/H mice, immunized with spinal cord homogenate or MOG35-55 peptide, by the caspase-1-inhibitor Z-Val-Ala-dl -Asp-fluoromethylketone, significantly reduces EAE incidence in a preventive but not in a therapeutic protocol. These results indicate that caspase-1 plays an important role in the early stage of the immune-mediated inflammatory process leading to EAE, thus representing a possible therapeutic target in the acute phase of relapsing remitting MS.

Amino Acid Chloromethyl Ketones↗
PubMed1999

Brain MRI correlates of magnetization transfer imaging metrics in patients with multiple sclerosis.

Previous studies suggested that magnetization transfer ratio (MTR) histograms are highly correlated with other magnetic resonance imaging (MRI) measures and can be used as a reliable method for quantifying overall disease burden in multiple sclerosis (MS). However, the relative influence of burden and severity of macroscopic MS lesions and degree of brain atrophy on various MTR histogram parameters has not yet been fully elucidated. Aim of the present study was to investigate which MRI measure best predicts the values of MTR histogram parameters in MS patients. Forty-two MS patients underwent brain dual-echo. T1-weighted and magnetization transfer imaging (MTI) MRI scans. Hyperintense lesion load (LL) on proton density (PD)-weighted and hypointense LL on T1-weighted images were measured using a local thresholding technique. A measure of brain atrophy was derived from T1-weighted images by computing the volume of brain tissue segmented from a slab of five consecutive slices rostral to the velum interpositum. On MTI scans, MTR histogram analysis was performed for the whole brain and average lesion MTR was also calculated. PD-weighted LL, T1-weighted LL and brain volume were significantly correlated with several MTI-derived measures. When a multivariate analysis was performed, brain volume alone significantly predicted the values of all the MTR histogram-derived measures (P values ranged from 0.003 to 0.0002). The ratio between hypointense T1-weighted and hyperintense PD-weighted LL significantly predicted average lesion MTR (P<0.05). Our results confirm that MTR can be used as a reliable method to assess both the overall disease burden and the individual lesion intrinsic nature in MS patients. The significant influence of brain atrophy on MTR histogram parameters supports the concept that this method also provides information on the loss of brain parenchyma in MS.

Adult↗