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Biomedical subjects

V Cosi

Publications and source records attributed to V Cosi.

At least 19 recordsLinked to original sources
PubMed2002

Ocular motor myotonic phenomenon in myotonic dystrophy.

OBJECTIVE: To detect disconjugate ocular motor abnormalities and a possible extraocular muscle myotonic phenomenon in patients with myotonic dystrophy (MyD). METHODS: The magnetic scleral search coil technique was used to record monocularly the small (25 degrees ) and large (50 degrees ) saccades, which were paced to two interstimulus intervals (ISIs), one short (1 s), the other long (5 s). The case study comprised 20 patients with MyD, 10 patients with multiple sclerosis (MS), and 10 controls. The amplitude, duration, peak velocity, and skewness of the velocity profile (ratio between the acceleration and the deceleration periods) of each saccade were measured. The disconjugate parameters (difference between the two eyes of the same measure), and the myotonic parameter (the maximal (as absolute value) short-long ISI difference between the same measures) were considered. RESULTS: The disconjugate parameters were the same in all three groups. The mean values of myotonic parameters found in patients with MyD for duration (for both small and large target displacements) and skewness (for small target displacements only) differed from those found for both the MS and the control groups. Additionally, the occurrence of individual patients presenting with abnormal duration and skewness parameters was higher in the MyD than in the MS group. In patients with MyD, the saccade duration was longer for long than for short ISI; the effect derived from a prolongation of the acceleration period, which manifested as an increase in skewness. CONCLUSION: The results can be explained by a combination of the myotonic and the warm up phenomena. A delay in the relaxation (myotonia) of the extraocular muscle may be more evident after a long fixation period (long ISI) and it may improve by increasing saccade pacing (short ISI-warm up). This phenomenon is slight, and is unlikely to affect saccade performance significantly, but it may provide some insight into the nature of the disorder affecting extraocular and skeletal muscles in myotonic dystrophy.

Adolescent↗
PubMed2001

Polymorphic markers in MHC class II/III region: a study on Italian patients with myasthenia gravis.

With an Italian case series of 81 Italian patients and 130 controls, we analysed associations between myasthenia gravis (MG) and genetic polymorphisms in the MHC class II/III region. Increases in the frequency of the TNF-B*1, C4A*Q0, C4B*1, DRB1*03 supratype, which is likely part of the 8.1 ancestral haplotype, were maximal in females with early onset (EO) MG vs. controls [p<0.05, relative risk (RR)=9.9]. These patients showed neither a significantly high frequency of thymic hyperplasia, nor high levels of serum anti-acethylcholine receptor antibodies. The DRB1*03 allele was absent in patients with thymoma; however, in comparison with controls, occurrence of this marker was frequent in MG patients (p<0.005; RR=6.2), more frequent in females (p<0.005; RR=7.8) and most frequent in EOMG female patients (p<0.005; RR=15.1). Analysis of the TNF-B*1, C4A*Q0, C4B*1, DRB1*03 supratype and its recombinants showed that the MHC region between C4 and TNF might contain genes that influence susceptibility to MG in females. Polymorphic markers within the supratype, e.g. TNF-B*1 and C4A*Q0, might contribute to pathogenetically significant abnormalities in immune responses in a subset of female MG patients. The combined effect of other intervening genes cannot be excluded.

Adult↗
PubMed2001

Predicting secondary progression in relapsing-remitting multiple sclerosis: a Bayesian analysis.

With the aid of a Bayesian statistical model of the natural course of relapsing remitting Multiple Sclerosis (MS), we identify short-term clinical predictors of long-term evolution of the disease, with particular focus on predicting onset of secondary progressive course (failure event) on the basis of patient information available at an early stage of disease. The model specifies the full joint probability distribution for a set of variables including early indicator variables (observed during the early stage of disease), intermediate indicator variables (observed throughout the course of disease, prefailure) and the time to failure. Our model treats the intermediate indicators as a surrogate response event, so that in right-censored patients, these indicators provide supplementary information pointing towards the unobserved failure times. Moreover, the full probability modelling approach allows the considerable uncertainty which affects certain early indicators, such as the early relapse rates, to be incorporated in the analysis. With such a model, the ability of early indicators to predict failure can be assessed more accurately and reliably, and explained in terms of the relationship between early and intermediate indicators. Moreover, a model with the aforementioned features allows us to characterize the pattern of disease course in high-risk patients, and to identify short-term manifestations which are strongly related to long-term evolution of disease, as potential surrogate responses in clinical trials. Our analysis is based on longitudinal data from 186 MS patients with a relapsing-remitting initial course. The following important early predictors of the time to progression emerged: age; number of neurological functional systems (FSs) involved; sphincter, or motor, or motor-sensory symptoms; presence of sequelae after onset. During the first 3 years of follow up, to reach EDSS> or =4 outside relapse, to have sphincter or motor relapses and to reach moderate pyramidal involvement were also found to be unfavourable prognostic factors.

Age of Onset↗
PubMed2001

Serum and CSF levels of MCP-1 and IP-10 in multiple sclerosis patients with acute and stable disease and undergoing immunomodulatory therapies.

The two chemokines, monocyte chemoattractant protein (MCP)-1 and gamma-interferon inducible protein (IP)-10, are thought to be involved in the pathogenesis of multiple sclerosis (MS). We measured MCP-1 and IP-10 levels in serum and CSF samples from 38 acute and 25 stable MS patients and from 40 controls. The latter consisted in patients with other inflammatory neurological diseases (OIND) or with non-inflammatory neurological diseases, and healthy controls. CSF MCP-1 levels exceeded those found in serum in all the patients studied as well as in healthy controls. CSF MCP-1 levels were significantly lower in acute MS [468+/-(S.E.M.) 18 pg/ml] than in stable MS (857+/-104 pg/ml). When detectable, serum and CSF IP-10 levels were significantly higher in acute MS (serum 331+/-66 pg/ml; CSF 118+/-16 pg/ml) than in stable MS (serum 69+/-7 pg/ml; CSF 25+/-2 pg/ml). Among OIND patients, those with HIV-1-associated dementia showed high serum and CSF levels of both MCP-1 and IP-10. Those with encephalitis showed high serum and CSF levels of IP-10 and CSF mononuclear pleiocytosis. We also evaluated the effects of 6-methylprednisolone or IFN-beta1a therapy on circulating MCP-1 and IP-10 levels. Neither MCP-1 nor IP-10 post-therapy levels varied significantly from baseline values. Our findings suggest that (a) MCP-1 could be constitutively produced within the brain; (b) MCP-1 and IP-10 CSF levels in acute MS vary significantly from those in stable MS, and these variations are inverse; and (c) current MS therapies do not modify circulating levels of MCP-1 and IP-10.

Acute Disease↗
PubMed2000

Usefulness of Bayesian graphical models for early prediction of disease progression in multiple sclerosis.

Previous studies of possible prognostic indicators for multiple sclerosis have been based on "classic" Cox's proportional hazards regression model, as well as on equivalent or simpler approaches, restricting their attention to variables measured either at disease onset or at a few points during follow-up. The aim of our study was to analyse the risk of reaching secondary progression in MS patients with a relapsing-remitting initial course, using two different statistical approaches: a Cox's proportional-hazards model and a Bayesian latent-variable model with Markov chain Monte Carlo methods of computation. In comparison with a standard statistical approach, our model is advantageous because, exploiting all the information gleaned from the patient as it is gradually made available, it is capable to detect even small prognostic effects.

Age of Onset↗
PubMed2000

Periodic alternating nystagmus and vestibulo-spinal system facilitating activity.

OBJECTIVE: Periodic alternating nystagmus has been associated with the instability of the velocity storage mechanism, which is known to play an important role in both the vestibulo-oculomotor and the optokinetic systems. In the present study we looked for a possible spinal equivalent to PAN. METHODS AND RESULTS: In 3 PAN patients, the H-reflex amplitude proved to be slightly but significantly influenced by nystagmus direction, in that it was greater when the nystagmus was beating toward the stimulation side. CONCLUSIONS: This finding suggests that projections from velocity storage may play a role not only in the ocular motor but also in assisting postural stability through the vestibulo-spinal system.

Adolescent↗
PubMed2000

Circadian and hypothermia-induced effects on visual and auditory evoked potentials in multiple sclerosis.

OBJECTIVES: Body cooling has been proposed as a symptomatic treatment for multiple sclerosis. This study aimed to assess the effects of body cooling and of circadian variations on clinical parameters and on visual and auditory evoked potential measures in multiple sclerosis patients. METHODS: Clinical status was assessed and VEPs, BAEPs and MLAEPs (all with two stimulus frequencies) were recorded a total of 4 times on two separate days (two times per day at 08:30 and 15:00 h each day) in 10 multiple sclerosis patients and 10 controls. On one of these days, the subjects were submitted to body cooling before the afternoon session. RESULTS: Tympanic temperature was significantly higher in the afternoon. Cooling lowered the temperature by 1.4 degrees C. No clinical effects were observed. Circadian effects were detected on VEP amplitude, which increased both in controls and in patients at low stimulus frequency (P<0.01), and increased in controls and decreased in patients at high stimulus frequency (interaction: P<0.01). Cooling determined an increase in BAEP I-V peak-to-peak time in controls, and a reduction in patients at high stimulus frequency (interaction: P<0.01). In patients, cooling also determined a great increase in MLAEP amplitude (interaction: P<0.001). We did not find cooling effects on VEP measures. CONCLUSIONS: Visual and auditory evoked potentials showed differences in circadian and cooling effects between controls and multiple sclerosis patients. These differences are consistent with the hypothesis of temperature-dependent conduction blocks in demyelinated fibers. Cooling may have a clinical effect in selected patients only.

Acoustic Stimulation↗
PubMed2000

Auditory saccade impairment after central thalamus lesions.

Visual and auditory saccades were studied in three patients with an isolated lesion located in the central thalamus. Visual saccades proved to be normal, whereas for auditory stimuli, the amplitude of the first saccade was asymmetric: saccades ipsilateral to the lesion were significantly smaller than those directed to the contralateral side. The patients were able to make a corrective saccade and hence to improve gain and to decrease gain asymmetry. It is suggested that patients were able to localise auditory targets correctly, but did not correctly take into account eye position during the saccade, probably as a consequence of an inaccurate efference copy (corollary discharge) signal. The findings are in keeping with the hypothesis that the central thalamus deals with saccades that are based on extraretinal signals.

Acoustic Stimulation↗
PubMed2000

Interferon-gamma and interleukin-4-producing T cells in peripheral blood of multiple sclerosis patients.

Pro- and anti-inflammatory cytokines are thought to participate in the development and regulation of autoimmunity in multiple sclerosis (MS), a demyelinating disease of the central nervous system (CNS). We analysed the percentage of interferon (IFN)-gamma and interleukin (IL)-4-producing cells in the peripheral blood of both active and stable MS patients, and of healthy controls. After short-term stimulation, cytokine-producing cells were intracellularly stained and sorted. Significantly lower percentages of IFN-gamma and IL-4-producing T cells were found in stable MS patients than in controls, and in active than in stable patients. The diminution affected CD4(+) (Th1, Th2) and CD8(+) (Tc1) phenotypes. Tc2 cells were not detected. The Th1/Th2 ratio did not differ in active and stable MS, nor in controls. The fact that Th2 and Tc1 cell percentages were higher in stable than in active MS possibly indicates that these cells play a downmodulating role in the immune response. In contrast, a role in exacerbating the immune response is not attributable to Th1 cells, given their reduction in acute MS. Our data do not support the hypothesis that MS is a Th1/Th2 paradigmatic disease; rather, they suggest that sequestration in the CNS, or activation-induced apoptosis (whether in vivo or in vitro) may explain reduced levels of IFN-gamma and IL-4-producing subsets in the peripheral blood of clinically acute patients.

Adolescent↗
PubMed1999

Amodal completion in texture visual evoked potentials.

Amodal completion refers to the phenomenological finding of perceiving partly occluded objects as continuing uninterrupted behind an occluder. The outlying problem is how the visual system processes such non-local stimuli because the known processes of early vision are spatially restricted operations which segregate local differences in the visual image, and little is known about their interactions in producing the segmentation of the image into functionally coherent, or global, objects. We recorded human visual evoked potentials (VEPs) to texture stimuli and addressed local/non-local relationships in comparing a condition in which local edges were present, due to texture segregation, with a condition in which, in addition to local edges, textures appeared to continue as surfaces behind gray stripes due to non-local amodal completion. Subtraction of offset from onset responses showed: (1) a difference component due to texture segregation characterized by a negativity with onset at about 95 ms and lasting up to about 280 ms; (2) a further negativity, specifically elicited by amodal completion, with onset at about 142 ms, peaking at 175 ms, and lasting up to about 188 ms. Therefore, amodal completion occurs at an early processing stage of image analysis and the difference component in VEPs can be related to figure-ground perception.

Adult↗
PubMed1999

Edge detection and surface 'filling in' as shown by texture visual evoked potentials.

OBJECTIVES: We designed a stimulation paradigm that was designed to ascertain whether specific components of the texture visual evoked potentials were attributable to edge detection or to surface 'filling-in' processes. METHODS: The stimuli were textures of parallel line elements, which were either uniform (all horizontal or vertical lines) or segregated (checkerboards in which texture line elements of neighbor checks were oriented orthogonally). A sequence of 4 stimuli, two uniform followed by two segregated stimuli, was repeated cyclically. Accordingly, segregation could appear from a uniform display; it could also be maintained, with the checkerboard illusory margin location unchanged but with alteration in the orientation of all line elements. Each stimulus was presented for 487 ms and instantly replaced by the following one. RESULTS: Segregation-related components for segregation-appearance (Sa) and for segregation-maintenance (Sm) conditions were obtained separately by subtraction. In both conditions, a negative component was obtained with a peak latency of about 140-150 ms. However, the onset of Sa was earlier than that of Sm, whereas the respective offsets were almost identical. CONCLUSIONS: We hypothesize that the segregation component in VEPs is composed of two subcomponents: an early part, which is related to the segregation of edges, and a final part, which is related to the 'filling-in' of the homogeneous texture surface within the boundary defined by these edges.

Adolescent↗
PubMed1999

TE671 cell-based ELISA for anti-acetylcholine receptor antibody determination in myasthenia gravis.

BACKGROUND: Acetylcholine receptor (AChR) from human muscles is the antigen used currently in radioimmunoprecipitation assays (RIPAs) for the determination of anti-AChR antibodies in the diagnosis of myasthenia gravis (MG). Our aim was to develop and validate an ELISA using TE671 cells as the source of AChR. METHODS: After TE671 cell homogenization, the crude AChR extract was used for plate coating. Anti-AChR antibodies were determined in 207 MG patients and in 77 controls. RESULTS: The mean intra- and interassay CVs (for two samples with different anti-AChR antibody concentrations) were 9.7% and 15.7%, respectively. Test sensitivity and specificity, for generalized MG, were 79.5% (95% confidence interval, 72.8-85.0%) and 96.1% (89.0-99.1%). The detection limit was 2 nmol/L. Anti-AChR antibody concentrations from 53 MG patients, as tested with our ELISA, showed good agreement with an RIPA with a mean difference (SD) of 1.0 (5.6) nmol/L. CONCLUSION: Our ELISA is a simple screening test for the diagnosis of MG and enables rapid and inexpensive patient follow-up.

Adolescent↗
PubMed1999

Tumor necrosis factor-alpha and its soluble receptors in plasma and cerebrospinal fluid of multiple sclerosis patients treated with methylprednisolone.

Demyelination is the main pathological feature of multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system. Tumor necrosis factor-alpha (TNF-alpha) can cause myelin damage and contribute to MS pathogenesis. We measured plasma and cerebrospinal fluid (CSF) levels of TNF-alpha and its soluble receptors, TNF-sRp55 and TNF-sRp75, in 18 patients with active MS, and in neurological and healthy controls. The same determinations were repeated on plasma and on CSF samples that were collected after the MS patients had ended a six-day treatment with high-dose methylprednisolone (MP). Pre- and post-treatment plasma and CSF TNF-alpha levels, when detectable, and those of TNF-sRp75, did not vary, and were similar to those of controls. CSF TNF-sRp55 levels were higher in acute MS patients than in controls. Post-treatment CSF TNF-sRp55 levels were higher than in the active phase of the disease. The MS patients, who clinically improved, tended to have the highest CSF TNF-sRp55 levels. The increase was due to intrathecal TNF-sRp55 synthesis. Although it is involved in MS pathogenesis, TNF-alpha is not detectable in plasma or in CSF samples from MS patients in various phases of the disease. A better marker of disease activity seems to be CSF TNF-sRp55 levels. The increased CSF levels of TNF-sRp55 in response to MP circumstantially suggest that this receptor could partially account for the beneficial effects of MP in acute MS.

Adult↗
PubMed1999

Opsoclonus in a patient with cerebellar dysfunction.

After two days of malaise, headache, nausea, and vomiting, a 26-year-old man suddenly developed opsoclonus and stance and gait ataxia, without myoclonus. Having excluded a paraneoplastic etiology, we assumed that the disorder was probably related to a viral infection. Spontaneous resolution occurred in about two months. Opsoclonus became flutter dysmetria and then resolved. Saccadic eye movement recording disclosed the occurrence of hypermetria, increased velocity, and delayed latency, which also resolved. In this patient, the correspondence between clinical and ocular motor abnormality courses suggests a transient cerebellar dysfunction as the possible pathophysiologic mechanism for opsoclonus.

Adult↗