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Biomedical subjects

G Comi

Publications and source records attributed to G Comi.

At least 307 records · Page 17Linked to original sources

Cardiac autonomic function during sleep and wakefulness in multiple sclerosis.

Some studies in multiple sclerosis (MS) patients have shown evidence of autonomic dysfunction involving the cardiovascular system. However, the findings in these studies have not been completely consistent. The discrepancy may be related to the limits of the traditional autonomic tests during wakefulness. In our study, after the investigation of the cardiovascular reflexes during wakefulness, heart rate (HR) variations were considered during sleep in order to avoid the limits of cooperation and the emotional state of the patient. We evaluated tonic (vagal activity) HR modifications in relation to the deepening of sleep, as well as phasic (sympathetic activity) HR modifications in relation to spontaneous body movements during sleep, in 25 MS patients and 25 age-matched controls. No difference was found between the two groups in autonomic function during wakefulness. A reduced parasympathetic activity was observed in MS subjects during both rapid eye movement (REM) and non-REM sleep, while no difference was found in sympathetic function between patients and controls. No significant correlation was found between cardiac autonomic data during sleep and MRI lesion load in the infratentorial areas and, in particular, of the brain stem. The findings of our study suggest that autonomic nervous system evaluation during sleep could show impairment earlier than the traditional autonomic tests during wakefulness.

Adult↗

Acute myelopathy of unknown aetiology: a clinical, neurophysiological and MRI study of short- and long-term prognostic factors.

Brain and spinal cord magnetic resonance imaging (MRI), multimodal evoked potentials (EPs) and cerebrospinal fluid (CSF) analysis were performed in 27 patients with acute myelopathy of unknown aetiology (AMUA), to detect the diagnostic and prognostic values of paraclinical tests at presentation. Spinal cord MRI was abnormal in 56% and brain MRI in 33% of the patients. Visual EPs were abnormal in 7%, median somatosensory EPs in 17%, tibial somatosensory EPs in 56% and motor EPs in 35% of the cases examined. Brain-stem acoustic EPs were normal in all the patients. CSF oligoclonal bands (OBs) were detected in 30% of cases. The patients were divided into subgroups according to the short-term clinical outcome (complete, partial or absent recovery). There were no significant differences among the three groups as regards MRI findings. Patients with complete recovery showed a significantly lower frequency of tibial somatosensory EP and motor EP abnormalities. According to the paraclinical findings at onset and on the basis of a long-term clinical follow-up (mean duration 24 months), 6 patients were diagnosed as having clinically definite multiple sclerosis, while 21 did not develop further neurological disturbances. Only the presence of CSF OBs was significantly more frequent in patients with definite multiple sclerosis. Our study indicates that EPs exploring spinal cord function are more powerful than spinal MRI for predicting the short-term outcome of AMUA, while the combined use of brain MRI and CSF OBs has the highest negative predictive value for the subsequent development of clinically definite multiple sclerosis.

Acute Disease↗

Genotype to phenotype correlations in mitochondrial encephalomyopathies associated with the A3243G mutation of mitochondrial DNA.

We studied 22 subjects carrying the A3243G point mutation of human mitochondrial DNA (mtDNA). In 14 cases the clinical phenotype was characterized by mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), while 8 patients had chronic progressive external ophthalmoplegia (CPEO). The proportion of A3243G heteroplasmy in muscle was determined by two methods; densitometry on a diagnostic restriction-fragment length polymorphism and solid-phase mini-sequencing. We found a highly significant inverse correlation between the percentage of A3243G mutation and the specific activity of complex I, the respiratory complex with the highest number of mtDNA-encoded subunits, suggesting a direct effect of the mutation on mtDNA translation. No correlation was observed between the percentage of mutated mtDNA and the presence or absence of specific clinical features, such as stroke, ophthalmoplegia and diabetes mellitus. However, in the MELAS group the percentage of mutated mtDNA molecules was strongly correlated with the age of onset, while no such correlation was found in the CPEO group, suggesting a different time-dependent evolution of the mutation in the two groups. Finally, in contrast with other mtDNA mutations associated with ragged-red fibres (RRF), in both MELAS3243 and CPEO3243 we observed a high proportion of RRF that were positive to the histochemical reaction to cytochrome c oxidase, a morphological feature that seems to be specific for the neuromuscular phenotypes associated with mutations affecting the tRNA(Leu(UUR)) gene.

Adolescent↗

Source model and scalp topography of pattern reversal visual evoked potentials to altitudinal stimuli suggest that infoldings of calcarine fissure are not part of VEP generators.

Visual evoked potentials (VEPs) to pattern reversal vertical bar stimuli were recorded from 19 scalp, 2 zygomatic and 3 inion derivations referenced to digitally linked earlobes in 50 controls. 1, 2 and 4 cycles per degree (cpd) patterns were presented as full field (FF) stimuli, on upper and lower hemifields (UHF-LHF), upper and lower quadrants and with the occlusion of central and peripheral UHF and LHF. VEPs to octant stimuli were also recorded with 2 cpd patterns. N1, P1 and N2 components were recorded from posterior and inion derivations with FF stimuli, from posterior derivations with LHF stimuli, only from inion leads with UHF stimuli, from derivations ipsilateral to stimuli with quadrants and octants, and from midline derivations only with lower quadrants. Polarity inverted sequences (iP1-iN1-iP2) were recorded from the other scalp derivations, with similar latency and spatial frequency sensitivity as N1-P1-N2. The orientation of Equivalent Dipoles (ED) was orthogonal with surface coordinates of mesial and occipito-polar calcarine cortex, measured on Magnetic Resonance Imaging. A model of VEP generators is proposed, suggesting that the VEP sequence is elicited only in mesial and occipito-polar surfaces of calcarine cortex.

Adult↗

P300 asymmetries in focal brain lesions are reference dependent.

In 6 patients with lesions of frontal, parietal and temporal lobe, in 4 patients affected by primary progressive aphasia (PPA) and in 56 age-matched controls, event-related potentials (ERPs) to an auditory odd-ball paradigm were recorded with the linked earlobe reference (LER) and with a computer calculated average reference (AR), excluding the two linked earlobe derivations. Latencies, amplitudes and scalp distribution of the earlier ERP components (P1, N1, P2, N2) were within normal limits for both LER and AR recordings. P300 scalp distribution in patients was normal when LER was used. When P300 was recorded using AR, the scalp distribution was statistically different from normal distributions in all patients. A negativity, instead of the positive P300 observed in controls, was recorded in patients from leads corresponding to the affected hemisphere.

Acoustic Stimulation↗

Brain MRI correlates of cognitive impairment in primary and secondary progressive multiple sclerosis.

Brain magnetic resonance imaging (MRI) and an extensive battery of neuropsychological tests exploring frontal functions, short and long-term memory, visuo-spatial skills, attention and language were applied to 14 patients with primary progressive multiple sclerosis (PPMS) and 17 patients with secondary progressive MS (SPMS). Patients with PPMS and SPMS did not differ in degree of physical disability, but cognitive deficits were found in 9/17 (53%) patients with SPMS and in only 1/14 (7%) of those with PPMS (p = 0.01). Patients with SPMS had higher total (p = 0.004), periventricular (p = 0.008) and non-periventricular (p = 0.04) MRI lesion loads than patients with PPMS. In detail, patients with SPMS had greater involvement of frontal (p = 0.05) and occipital (p = 0.02) horns, trigones (p = 0.04), third ventricle (p = 0.03), basal ganglia (p = 0.02), parietal (p = 0.02), temporal (p = 0.004) and occipital (p = 0.03) lobes. Patients with SPMS and neuropsychological deficits had higher non-periventricular lesion loads than patients with SPMS who did not have such deficits (p = 0.005). Our results indicate that both neuropsychological and brain MRI abnormalities are more extensive in patients with SPMS. Since physical disability was similar for both groups, disability in PPMS may be predominantly due to spinal cord involvement.

Adult↗

Interferon-gamma induces T lymphocyte proliferation in multiple sclerosis via a Ca(2+)-dependent mechanism.

The intracellular mechanisms underlying T lymphocyte activation leading to demyelination in multiple sclerosis (MS) have not yet been clarified. We have recently reported that interferon (IFN)-gamma activates a novel trans-plasmalemma Ca2+ influx on T lymphocytes (mainly CD4+) from patients with MS which induces intracellular Ca2+ ([Ca2+]i) elevation. Since Ca2+ is an essential second messenger in regulating transcription of T lymphocyte activation genes, we have evaluated how [Ca2+]i elevation due to the activity of this particular influx affects T lymphocyte proliferative behaviour in 12 influx-positive relapsing-remitting MS (RR-MS) patients. Fourteen influx-negative RR-MS patients and 14 healthy donors were used as controls. In lymphocytes from healthy controls, a significant correlation (r = 0.62; P < 0.001) was found between [Ca2+]i levels and proliferation rate after phytohemagglutinin (PHA) stimulation. Sustained proliferation was induced in T lymphocytes by > or = 10 micrograms/ml of PHA, a dose leading to a [Ca2+]i increase of at least 45% over basal level. Similar [Ca2+]i elevations were obtained when > or = 10 micrograms/ml of PHA were used on cells from RR-MS patients. However, T lymphocytes from RR-MS patients, but not from healthy donors, proliferated also in response to 1 micrograms/ml of PHA, indicating a state of preactivation. Moreover, 1 microgram/ml of PHA used in combination with suboptimal doses of IFN-gamma (5 UI/ml) doubled the proliferation rate of influx-positive MS cells, but not influx-negative MS cells or cells from healthy donors compared to the values obtained using PHA alone (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Utrophin expression during human fetal development.

Utrophin, a protein encoded by chromosome 6 is highly homologous to the cysteine-rich domain and most of the C-terminal domain of dystrophin. In order to clarify its functional role we analyzed its expression during human fetal development. We carried out immunohistochemical analysis on muscle from normal human fetuses at different ages of gestation using an antibody directed against a specific COOH-terminal sequence of the protein. In addition, we stained serial sections with antibodies against dystrophin and alpha-bungarotoxin FITC-BTX. Our findings show that, at week 9 of gestation, utrophin is diffusely expressed in the cytoplasm. From week 12 to 22 the immunostaining is still cytoplasmic, though the reaction intensity progressively decreases. Moreover we observed a strong reaction in fetal nerve at week 18 and 22. There was no correlation between utrophin expression and progressive dystrophin membrane localization.

Amino Acid Sequence↗

Intra- and inter-observer agreement of brain MRI lesion volume measurements in multiple sclerosis. A comparison of techniques.

The measurement of MRI lesion load in multiple sclerosis is increasingly being used to evaluate the natural history of the disease and to monitor the efficacy of treatments. If, as might occur in multicentre studies, lesion load is measured by several observers in different patients or by the same observer in serial scans, it would be necessary to utilize a technique which provides results with high inter- and intra-observer agreements. This study was performed to evaluate the intra- and inter-observer agreement of semi-automated lesion volume measurement using thresholding, and to compare them with those obtained using an arbitrary scoring system (ASS) and a quantitative manual tracing method (MTM). Brain MRIs were obtained for 20 clinically definite multiple sclerosis patients and were evaluated independently by three observers. The median intra- and inter-observer agreements were, respectively, 88.5% (range 69.0-96.8%) and 79.0% (range 73.3-98.3%) using the ASS, 95.0% (range 85.1-99.4%) and 93.4% (range 77.3-98.3%) for the MTM, 96.3% (range 94.2-98.9%) and 93.7% (range 83.8-98.3%) for the semi-automated technique. The intra- and inter-observer agreements for the semi-automated technique increased to 98.5% (range 96.3-99.8%) and 96.1% (range 90.5-98.6%) when a consensus in the choice of threshold for lesion segmentation was reached. The intra- and inter-observer agreements were significantly greater for the semi-automated method compared with both the arbitrary scoring and the MTMs. The intra-observer variability for the semi-automated technique was significantly lower (P < 0.0001) than the inter-observer variability obtained using the same technique. These data indicate that it is possible to obtain high intra- and inter-observer agreements using a semi-automatic thresholding technique to quantify lesion volumes in multiple sclerosis. The technique may prove useful in multicentre studies, in which a single observer is still preferable.

Brain↗

Transitional progressive multiple sclerosis: MRI and MTI findings.

Transitional progressive multiple sclerosis (MS) is quite an unusual form of presentation and course of the disease. A case with this progressive form is presented and brain MRI and MTI findings are discussed in relation to the possible insight they may provide for understanding the mechanisms that determine progressive disability in MS.

Adult↗

A brain MRI study of different types of chronic-progressive multiple sclerosis.

INTRODUCTION: This study was performed to define the pattern of brain magnetic resonance imaging (MRI) abnormalities in chronic-progressive MS (MS). MATERIAL AND METHODS: Brain MRIs were obtained for 17 patients with secondary progressive MS (SPMS), 14 with primary progressive MS (PPMS) and 5 with "transitional" progressive MS (TPMS). RESULTS: Total lesion loads were different for the three groups of patients (p < 0.01). At post-hoc analysis, there was no difference between patients with TPMS and those with PPMS, while both these groups had lesion loads lower than those of patients with SPMS. Patients with PPMS with clinical signs indicating involvement of both brain and spinal cord had greater total lesion loads than those with clinical isolated spinal cord involvement (p < 0.05). CONCLUSION: These data indicate that brain MRI patterns of abnormalities are related to the clinical manifestations in patients with chronic-progressive MS.

Adult↗

Brain magnetic resonance imaging and multimodal evoked potentials in benign and secondary progressive multiple sclerosis.

Brain MRI and multimodal evoked potentials (EPs) were obtained for 13 patients with benign multiple sclerosis and 13 patients with secondary progressive multiple sclerosis, matched for age and duration of the disease, to investigate the nature of the disability in multiple sclerosis. Patients with secondary progressive multiple sclerosis had significantly greater lesion loads for five of seven periventricular regions and for three of nine regions separate from the ventricles. Patients with secondary progressive multiple sclerosis also had more severe infratentorial atrophy scores (p = 0.04), whereas there were no differences between the two groups in number and extent of enhancing lesions. The frequencies were significantly higher and severities greater for multimodal EP abnormalities of all the modalities in patients with secondary progressive multiple sclerosis. At least one EP component was absent in 12 (92%) patients with secondary progressive multiple sclerosis but in only one patient (8%) with benign multiple sclerosis (p < 0.001). There was neurophysiological evidence for cervical cord involvement in eight (61%) patients with secondary progressive multiple sclerosis and in one with benign multiple sclerosis (p < 0.01). These data indicate that the total amount of lesions, the distribution, and the nature of the pathological process might all account for the development of disability in multiple sclerosis.

Age of Onset↗

Does hemispheric dominance influence brain lesion distribution in multiple sclerosis?

To evaluate whether hemispheric lesion distribution in multiple sclerosis is related to the uneven interhemispheric localisation of cerebral function, a 10 item self administered questionnaire evaluating hand preference and supratentorial brain MRI was obtained in 23 patients with clinically definite multiple sclerosis. The mean degree of hand preference was +74 (range -86 to +100). The median lesion volumes were 7275 (range 1045-22,440) mm3 for the left hemisphere and 5385 (range 1010-19,490) mm3 for the right hemisphere. The degree of hand preference correlated with the index of interhemispheric lesion distribution (P = 0.02). The data suggest that local events, possibly related to specialisation of hemispheric function, might be responsible for the increased vulnerability of the dominant hemisphere to the pathological process of multiple sclerosis.

Adolescent↗

Comparison of triple dose versus standard dose gadolinium-DTPA for detection of MRI enhancing lesions in patients with primary progressive multiple sclerosis.

This study was performed to evaluate whether a triple dose of gadolinium-DTPA (Gd-DTPA) increases the sensitivity of brain MRI for detecting enhancing lesions in patients with primary progressive multiple sclerosis (PPMS). T1 weighted brain MRI was obtained for 10 patients with PPMS in two sessions. In the first session, one scan was obtained five to seven minutes after the injection of 0.1 mmol/kg Gd-DTPA (standard dose). In the second session, six to 24 hours later, one scan before and two scans five to seven minutes and one hour after the injection of 0.3 mmol/kg Gd-DTPA (triple dose) were obtained. Four enhancing lesions were detected in two patients when the standard dose of Gd-DTPA was used. The numbers of enhancing lesions increased to 13 and the numbers of patients with such lesions to five when the triple dose of Gd-DTPA was used and to 14 and six in the one hour delayed scans. The mean contrast ratio for enhancing lesions detected with the triple dose of Gd-DTPA was higher than those for lesions present in both the standard dose (P < 0.0009) and the one hour delayed scans (P = 0.04). These data indicate that with a triple dose of Gd-DTPA many more enhancing lesions can be detected in patients with PPMS. This is important both for planning clinical trials and for detecting the presence of inflammation in vivo in the lesions of such patients.

Adult↗

Neurophysiologic studies and cognitive function in congenital hypothyroid children.

Minor neurologic and intellectual impairments have been described in some congenital hypothyroid (CH) children in spite of early detection by neonatal screening. The aim of our study was to assess cognitive functions as well as neurophysiologic parameters in hypothyroid children and to compare children detected by neonatal screening (group A) versus hypothyroid patients clinically diagnosed before the beginning of the screening program (group B). Group A consisted of 15 children (13 girls, mean age at the beginning of treatment 33 d). Group B consisted of 11 patients (7 girls, mean age at the start of treatment 10.1 mo). Twenty age-matched healthy children were studied as a control group for neurophysiologic tests. Neurophysiologic tests (Auditory P 300, long latency somatosensory evoked potentials (LL-SEP) were performed along with IQ evaluation. Abnormalities of neurophysiologic tests were detected in 82% of clinically diagnosed hypothyroid children. Surprisingly, 47% of the children detected by neonatal screening, having normal mental development index, showed at least one abnormal neurophysiologic test. LL-SEP latencies were found significantly increased in both groups of CH patients compared with controls. Our data are suggestive for a prenatal or perinatal CNS damage in some children with congenital hypothyroidism, despite early treatment.

Case-Control Studies↗

A magnetization transfer imaging study of normal-appearing white matter in multiple sclerosis.

We attempted to define the role of subtle changes in the normal-appearing white matter (NAWM) in the development of disability in multiple sclerosis (MS). Twenty-seven clinically definite MS patients with either relapsing-remitting or chronic-progressive courses and 10 sex- and age-matched controls entered the study. For each patient and control, we studied two NAWM areas in the frontal lobe with magnetization transfer imaging (MTI). For patients, we also calculated the MT ratios (MTRs) for three contiguous areas of NAWM progressively further from "isolated" lesions visible on conventional MRI. Frontal NAWM in MS patients had lower mean MTRs than the frontal white matter of the controls (p = 0.02). MTRs in the NAWM adjacent to isolated lesions increased with distance from them to the cortical gray matter (p = 0.04). This pattern was typical for patients with chronic-progressive MS whose MTRs in the first two regions of NAWM adjacent to lesions were lower than those of the same regions of patients with relapsing-remitting MS. This study confirms that there are alterations in the NAWM of MS patients and suggests that such changes might be relevant to the disability in MS.

Adult↗

Visual evoked potentials generator model derived from different spatial frequency stimuli of visual field regions and magnetic resonance imaging coordinates of V1, V2, V3 areas in man.

Visual evoked potentials (VEPs) to pattern reversal vertical bar stimuli were recorded from 24 scalp derivations (including zygomatic and inion) referenced to digitally linked earlobes in 50 controls. 1, 2 and 4 cpd patterns were presented as full field (FF) stimuli, on Upper Hemifields (UHF) and Lower Hemifields (LHF), upper and lower quadrants and with the occlusion of central and peripheral UHF and LHF. VEPs to octant stimuli were also recorded with 2 cpd patterns. N1, P1 and N2 components were recorded from posterior and inion derivations with FF stimuli, from posterior derivations with LHF stimuli, only from inion leads with UHF stimuli, from derivations ipsilateral to stimuli with quadrants and octants, and consistently from midline derivations only with lower quadrants. Polarity inverted sequences (iN1-iP1-iN2) were recorded from the other scalp derivations, with similar latency and spatial frequency sensitivity as N1-P1-N2. Single Equivalent Dipole (ED) calculations were performed on N1 and P1 recorded in the different stimulus conditions. Our findings contradict previous hypotheses on VEP generators and contradict the predictions of VEPs polarity and distribution based on the "cruciform model" of VEPs generators. In order to explain the distribution of VEPs to upper and lower half fields and to quadrant and octants, we propose a model based on the position of the medial and occipito-polar surface of visual cortex in man.

Adult↗