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G Comi

Publications and source records attributed to G Comi.

At least 127 records · Page 7Linked to original sources

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↗

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↗

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↗

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↗

Relevance of interleukin 1 receptor antagonist intron 2 polymorphism in Italian MS patients.

The A1/A1 genotype of the anti-inflammatory cytokine interleukin 1 receptor antagonist (IL-1Ra) polymorphism was more frequent in 339 Italian MS patients than in healthy controls (HCs) (odds ratio = 1.83). A more aggressive disease course was also associated with A1+ genotypes and might reflect the reduced ability of mononuclear cell cultures of A1+ HCs to produce IL-1Ra. We conclude that an IL-1Ra gene polymorphism is associated with occurrence of disease and clinical course variability in Italian MS patients.

Adult↗

Short-term evolution of new multiple sclerosis lesions enhancing on standard and triple dose gadolinium-enhanced brain MRI scans.

We compared the short-term magnetic resonance imaging (MRI) evolution of new multiple sclerosis (MS) lesions enhancing after single dose (SD) (0.1 mmol/kg) or triple dose (TD) (0.3 mmol/kg) gadolinium-DTPA (Gd) to explore possible differences in the pathological substrates of acute MS lesions. Brain MRI scans were obtained at baseline and every 4 weeks for a 3-month period in 18 relapsing-remitting MS patients. At each time point, using two separate sessions, we obtained dual echo and T1-weighted scans before and after SD and TD of Gd. New enhancing lesions detected at month 1 and 2 were entered into the analysis. The presence of corresponding hypointense lesions on unenhanced T1-weighted scans and hyperintense lesions on T2/proton density (PD)-weighted images was assessed on the same scan and on the scans performed 1 month before and 1 month after the new lesion development. Persistence of enhancement was evaluated on the SD and TD scans obtained 1 month after new lesion appearance. One-hundred and sixty lesions were studied. Of these, 97 lesions were enhancing after both SD and TD (group A) and 63 lesions only after TD (group B). Thirty (31%) of the lesions enhancing after both SD and TD and ten (16%) of the lesions enhancing only after TD had corresponding T1-weighted lesions (P = 0.03). Of these lesions, 87% in group A and 40% in group B (P = 0.003) were not hypointense on the previous scans. No differences were found in the frequencies of corresponding T2/PD-weighted abnormalities (92% in Group A vs. 87% in Group B lesions). Of these hyperintense areas, 62% in group A and 56% in group B were not present on the previous scans. On follow-up scans, 52% of the lesions enhancing after SD and TD and 70% of the lesions enhancing only after TD did not show enhancement after the injection of both the doses of Gd (P = 0.02). The frequencies of corresponding T2/PD and T1-weighted abnormalities were higher in Group A than in Group B lesions, but the differences were not statistically significant. Our findings suggest that the pathological process is less severe in MS lesions enhancing only after TD injection than in those enhancing after the SD.

Adult↗

Magnetization transfer imaging of patients with definite MS and negative conventional MRI.

OBJECTIVE: To assess, in a group of patients with clinically or laboratory-supported definite MS and negative conventional MRI scans of the brain, whether magnetization transfer imaging (MTI) is able to detect subtle white matter changes. BACKGROUND: MTI of the brain in patients with MS frequently demonstrates the presence of microscopic damage to white matter, which appears normal on conventional MRI. METHODS: Brain MRI and MTI scans were obtained from 11 patients with negative conventional MRIs of the brain, selected from 618 clinically or laboratory-supported definite MS cases scanned in the last 2 years in three Italian MS centers. RESULTS: Compared with control subjects, patients had significantly lower mean MT ratios (MTR) in the pons, cerebellum, and periventricular regions. The percentages of pixels with MTR values below 1, 2, and 3 SD of the mean MTR value of the control subjects were 7.6% (range, 3.2% to 11.8%), 5.2% (range, 2.0% to 8.5%), and 3.6% (range, 1.2% to 6.1%), respectively. They were mainly located in the white matter of the centra semiovalia, and usually were isolated. CONCLUSIONS: MTI can detect white matter abnormalities in patients with MS and negative conventional brain MRI scans. The detection of such abnormalities may increase diagnostic confidence in those cases where MS is clinically suspected, but conventional MRI does not suggest the diagnosis.

Adolescent↗

Study on volatile components in salami by reverse carrier gas headspace gas chromatography-mass spectrometry.

Salami are a typical seasoned sausage of Italy; a number of types are produced, according to local traditional recipes. As industrial production has taken place, a number of problems rise in obtaining products similar to the traditional ones. The use of selected microbial starters is permitted by Italian law for some years and at present, microbiological research is engaged in selecting starters similar to the ones isolated from traditional products, with the aim of obtaining organoleptic characteristics close to the ones of traditional recipes. A study was carried out concerning the characterisation of volatile components of salami by headspace capillary gas chromatography-mass spectrometry. As during the sampling step, analytes could reach the analytical column, the carrier gas rate was back flushed in the latter, while a pre column was used as cold trap. Then GC-MS analysis follows. By these techniques, we were able to highlight typical profiles of different salami, as well as monitoring the ripening of a traditional and a starter added salami. Main peaks are of fermentative origin, while also peaks from spices were detected. Ethyl propionate was used as internal standard to be able to normalise the peaks amounts.

Gas Chromatography-Mass Spectrometry↗

A comparison of the sensitivity of monthly unenhanced and enhanced MRI techniques in detecting new multiple sclerosis lesions.

In this longitudinal study, the sensitivities of three magnetic resonance imaging techniques for detecting the appearance of new lesions in multiple sclerosis (MS) were evaluated and compared. Dual-echo conventional spin-echo (CSE), fast fluid-attenuated inversion recovery (fast-FLAIR) and post-contrast T1-weighted scans were obtained on four occasions, each separated by 28 days, from 18 patients with relapsing-remitting MS using a 1.5-T machine. New lesions seen using each sequence during the follow-up were counted by agreement by four observers in two stages (stage 1: random review of complete sets of scans from each technique; stage 2: side-by-side review with a 'retrospective' count of new lesions). At stage 1, 1.44 new lesions per patient per month were detected on CSE scans, 1.88 on fast-FLAIR (31% more than CSE) and 2.07 on post-contrast T1-weighted scans (44% more than CSE) (P = 0.03). Differences were, however, reduced after stage 2: fast-FLAIR detected 29% and post-contrast T1-weighted scans detected 31% more new lesions than CSE(P = 0.08). The combination of fast-FLAIR and post-contrast scans detected 144 new lesions, whilst the usual combination of CSE and post-contrast scans detected 133 new lesions. This study indicates that enhanced MRI remains the most sensitive method for detecting 'active' lesions in MS and that fast-FLAIR may be used when monitoring short-term disease activity in MS, either natural or modified by treatment.

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↗

Long-term follow-up of isolated optic neuritis: the risk of developing multiple sclerosis, its outcome, and the prognostic role of paraclinical tests.

We evaluated the risk of developing clinically definite multiple sclerosis (CDMS) after an acute attack of isolated optic neuritis (ON) in 112 patients, in relation to demographic and paraclinical findings. Patients were examined by brain MRI, CSF analysis, and multiple evoked potentials (EPs); 10 were lost to follow-up, and the other 102 were enrolled in a prospective study (follow-up duration 6. 3 +/- 2.2 years). Of these, 37 (36.3%) developed CDMS after a mean interval of 2.3 +/- 1.6 years. The risk of developing CDMS was 13% after 2 years, 30% after 4, 37% after 6, and 42% after 8 and 10 years. Gender, age, and season of ON onset did not affect the risk. MS occurred in 37 of 71 patients (52.1%) with one MRI lesion or more; no patient with a normal MRI developed the disease. MS developed more frequently in patients with intrathecal IgG synthesis than in those without (43% vs. 28%), but the difference was not statistically significant. Multiple EPs showed a slight predictive value only including somatosensory EPs of the lower limb. Multiple sclerosis was mild in most cases (EDSS 2.2 +/- 1.9). The EDSS was less than 4 in 32 cases (86%), between 4 and 6 in 2 (5%), higher than 6.5 in 3 (8%).

Adult↗

Introduction

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Journal Article↗

Neurophysiological imaging techniques in dementia.

Neurophysiological methods, such as electroencephalography (EEG) and event-related potentials, are useful tools in the investigation of brain cognitive function in normal and pathological conditions, with an excellent time resolution when compared to that of other functional imaging techniques. Advanced techniques using a high number of EEG channels also enable a good spatial resolution to be achieved. This, together with the possibility of integration with other anatomical and functional images, may increase the ability to localize brain functions. Spectral analysis of the resting EEG, which gives information on the integrity of the cortical and subcortical networks involved in the generation of cortical rhythms, has the limitation of low sensitivity and specificity for the type of cognitive impairment. In almost all types of dementia, decreased power of the high frequencies is indeed observed in mild stages, accompanied by increased power of the slow rhythms in the more advanced phases. The sensitivity for the detection of spectral abnormalities is improved by studying centroid modifications. More specific information on the type of dementia can be provided by coherence analysis of the resting EEG, a measure of functional cortico-cortical connections, which has different abnormal patterns in Alzheimer's disease, cerebrovascular dementia and dementia associated with multiple sclerosis. Another tool for improving the assessment of demented patients is the study of EEG activity related to particular tasks, such as event-related potentials and event-related desynchronization/synchronization of the EEG, which allow the study of brain activation during cognitive and motor tasks.

Brain↗

Lesion load measurements in multiple sclerosis: the effect of incorporating magnetization transfer contrast in fast-FLAIR sequence.

We compared the ability and reproducibility of a fast fluid-attenuated inversion recovery (fast-FLAIR) sequence with and without a magnetization transfer (MT) pulse for detecting and measuring multiple sclerosis (MS)-related abnormalities on magnetic resonance imaging (MRI) scans from 20 patients. The Contrast-to-Noise ratios between lesions and normal-appearing white matter, lesion numbers, lesion volumes and the variability of such measurements were similar for the two sequences. This suggests that the addition of MT to FLAIR sequences as currently implemented on standard MRI scanners does not improve the detection of MS lesions.

Adult↗

A longitudinal study comparing the sensitivity of CSE and RARE sequences in detecting new multiple sclerosis lesions.

In this longitudinal study, we evaluated the sensitivities of dual-echo, conventional spin-echo (CSE), and rapid-acquisition relaxation-enhanced (RARE) scans for detecting the appearance of new lesions in multiple sclerosis (MS). Dual echo, CSE, and RARE scans were obtained on four occasions each separated by 28 days from five patients with relapsing-remitting MS using a 1.5-Tesla machine. A total of 44 new lesions were detected by the two sequences. Thirty-five lesions were seen on both sequences, three only on CSE and six only on FSE. This study indicates that CSE may be substituted by RARE when monitoring short-term disease activity in MS.

Brain↗

Correlation between enhancing lesion number and volume on standard and triple dose gadolinium-enhanced brain MRI scans from patients with multiple sclerosis.

We investigated the correlations between numbers and volumes of multiple sclerosis (MS) lesions enhancing on standard dose (SD) and triple dose (TD) gadolinium (Gd)-enhanced brain magnetic resonance imaging (MRI) scans, to clarify whether the measurement of enhancing lesion volumes or the use of TD MRI give additional information which can not be obtained by counting enhancing lesions on SD scans. SD and TD Gd-enhanced brain MRI scans were obtained every month for three months from 40 MS patients. The numbers of total and new enhancing lesions were counted, and the total volumes of enhancing lesions were measured from each of the four scans obtained with the two techniques. Univariate correlations between enhancing lesion numbers and volumes were assessed. The numbers of total and new enhancing lesions seen either on SD or TD scans were significantly correlated (r = 0.91 and 0.93, respectively). The numbers and volumes of total enhancing lesions were significantly correlated on both SD (r = 0.90), and TD (r = 0.89) scans. Moderate correlations were found between the total number of enhancing lesions on SD scans and the average difference between TD and SD scans for total enhancing lesion number (r = 0.66), and between the number of new enhancing lesions on SD scans and the average difference between TD and SD scans for new enhancing lesion number (r = 0.50). Our findings indicate that, both on SD and TD MRI, the counts and the volumes of total and new enhancing lesions are highly correlated, and that lesion counting may suffice to monitor MS activity. On the contrary, this study confirms the usefulness of TD MRI for a more complete assessment of the acute changes occurring in MS patients.

Brain↗

Short-term evolution of individual enhancing MS lesions studied with magnetization transfer imaging.

We performed serial monthly magnetization transfer (MT) imaging to evaluate the prevalence and evolution of structural changes in individual enhancing lesions from patients with multiple sclerosis (MS). Every 4 weeks for 3 months, we obtained dual echo, magnetization transfer (MT) imaging and, 5 min after SD (0.1 mmol/kg) gadolinium-DTPA injection, T1-weighted scans from 10 patients with early relapsing-remitting MS. We measured the MT ratio (MTR) of enhancing lesions seen on the entry scans on co-registered quantitative MTR images at entry and during the follow up. Fourty-two enhancing lesions were identified on the entry scans. According to the "maximal random fluctuation" detected for the normal-appearing white matter MTR values, 16 (38%) lesions were classified as "increasing MTR" lesions, 21 (50%) as "stable MTR" lesions, and 5 (12%) as "decreasing MTR" lesions. The classification of the lesions after the first month of follow up strongly predicted the classification at the end of the follow up (chi squared = 20.35, p = 0.0004). These results indicate that the enhancing lesion population in MS is heterogeneous, and that reparative mechanisms occurring after blood-brain barrier opening are not efficient in only a minority of the enhancing lesions from patients with early relapsing-remitting MS.

Adult↗