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X Montalban

Publications and source records attributed to X Montalban.

At least 19 recordsLinked to original sources
PubMed2001

Altered inflammatory response and increased neurodegeneration in metallothionein I+II deficient mice during experimental autoimmune encephalomyelitis.

Metallothionein-I+II (MT-I+II) are antioxidant, neuroprotective proteins, and in this report we have examined their roles during experimental autoimmune encephalomyelitis (EAE) by comparing MT-I+II-knock-out (MTKO) and wild-type mice. We herewith show that EAE susceptibility is higher in MTKO mice relatively to wild-type mice, and that the inflammatory responses elicited by EAE in the central nervous system (CNS) are significantly altered by MT-I+II deficiency. Thus, during EAE the MTKO mice showed increased macrophage and T-lymphocytes infiltration in the CNS, while their reactive astrogliosis was significantly decreased. In addition, the expression of the proinflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha elicited by EAE was further increased in the MTKO mice, and oxidative stress and apoptosis were also significantly increased in MTKO mice compared to normal mice. The present results strongly suggest that MT-I+II are major factors involved in the inflammatory response of the CNS during EAE and that they play a neuroprotective role in this scenario.

Animals↗
PubMed2001

Treatment with anti-interferon-gamma monoclonal antibodies modifies experimental autoimmune encephalomyelitis in interferon-gamma receptor knockout mice.

The role of interferon-gamma (IFN-gamma) in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) is still controversial. We have studied the function of IFN-gamma and its receptor in the EAE model using two different IFN-gamma receptor knockout (IFN-gamma R(-/-)) mouse types: C57Bl/6x129Sv, with a disruption of the IFN-gamma receptor cytoplasmic domain, and 129Sv, homozygous for a disrupted IFN-gamma receptor gene. Mice were immunized with peptide 40-55 from rat myelin oligodendrocyte glycoprotein. A subgroup of mice was treated with anti-IFN-gamma monoclonal antibodies (mAb) on day 8 postimmunization. Clinical scoring and both histological and immunohistochemical studies were undertaken for all groups. We hereby show that treatment with anti-IFN-gamma mAb worsened the disease course of 129Sv wild-type mice. However, it decreased the mean daily score in IFN-gamma R(-/-) 129Sv and the incidence of the disease down to 50% in C57Bl/6x129Sv IFN-gamma R(-/-) mice. Moreover, after anti-IFN-gamma mAb treatment, oxidative stress levels, metallothionein I and II antioxidant protein expression, and apoptoticneuronal death were increased in wild-type mice while decreased in IFN-gamma R(-/-) mice. These results suggest a putative alternative mechanism of action of this cytokine that works independent of its receptor.

Animals↗
PubMed2001

Similar pro- and anti-inflammatory cytokine production in the different clinical forms of multiple sclerosis.

Cytokines play an important role in the initiation and maintenance of the inflammatory reaction in multiple sclerosis, a chronic inflammatory demyelinating disease of the central nervous system. Magnetic resonance imaging evidence supports clinical divergence between forms of multiple sclerosis with relapses and the primary progressive form without relapses, which shows fewer and smaller inflammatory lesions. With the aim of understanding better the relative role of pro-inflammatory and/or anti-inflammatory cytokines in primary progressive multiple sclerosis in comparison to relapsing forms, we analysed in 65 patients (24 primary progressive, 20 relapsing-remitting and 21 secondary progressive) and 29 healthy controls, the production of cytokines (IFN-gamma, TNF-alpha, IL-6, IL-10 and IL-12) by peripheral blood mononuclear cells after in vitro stimulation. We found a similar percentage of cytokines producing cells between healthy controls and the different clinical forms of multiple sclerosis patients.

Adult↗
PubMed2001

Isolated demyelinating syndromes: comparison of CSF oligoclonal bands and different MR imaging criteria to predict conversion to CDMS.

AIM OF THE STUDY: To evaluate and compare the capacity of oligoclonal bands (OB) and three sets of MR imaging criteria to predict the conversion of clinically isolated syndromes (CIS) to clinically definite multiple sclerosis (CDMS). PATIENTS AND METHODS: One hundred and twelve patients with CIS were prospectively studied with MR imaging and determination of OB. Based on the clinical follow-up (conversion or not conversion to CDMS), we calculated the sensitivity, specificity accuracy, positive and negative predictive value of the OB, and MR imaging criteria proposed by Paty et al, Fazekas et al and Barkhof et al. RESULTS: CDMS developed in 26 (23.2%) patients after a mean follow-up of 31 months (range 12-62). OB were positive in 70 (62.5%) patients and were associated with a higher risk of developing CDMS. OB showed a sensitivity of 81%, specificity of 43%, accuracy of 52%, positive predictive value (PPV) of 30% and negative predictive value (NPV) of 88%. Paty and Fazekas criteria showed the same results with a sensitivity of 77%, specificity of 51%, accuracy of 57%, positive predictive value of 32% and negative predictive value of 88%. Barkhof criteria showed a sensitivity of 65%, specificity of 70%, accuracy of 69%, PPV of 40% and NPV of 87%. The greatest accuracy was achieved when patients with positive OB and three or four Barkhof's criteria were selected. CONCLUSIONS: We observed a high prevalence of OB in CIS. OB and MR imaging (Paty's and Fazekas' criteria) have high sensitivity. Barkhof's criteria have a higher specificity. Both OB and MR imaging criteria have a high negative predictive value.

Adolescent↗
PubMed2001

Anticardiolipin antibodies are not a useful screening tool in a nonselected large group of patients with multiple sclerosis.

Recent works claiming that primary antiphospholipid syndrome (PAPS) cannot be clinically distinguished from multiple sclerosis (MS) recommend that MS patients be screened for anticardiolipin antibodies (ACA). In this study 296 randomly selected patients with MS and clinically isolated syndromes and 51 healthy controls were analyzed; ACA, anti-beta2-glycoprotein I, or antiprothrombin was found in 6 patients. No predominance of any kind of clinical manifestations and no cardinal manifestations of PAPS were found in these patients. ACA tests should be performed only when a suspicion of PAPS is raised and atypical clinical presentation for MS is found.

Adult↗
PubMed2000

CD4(+)CD45RO(+)CD49d(high) cells are involved in the pathogenesis of relapsing-remitting multiple sclerosis.

In the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis, encephalitogenic T cells differ from the non-encephalitogenic ones in their expression of CD49d. The disease-inducing CD49d(high) and not the CD49d(low) cells enter the brain parenchyma. In this context, we characterized CD4(+)(CD45RO(+))CD49d(high) cells in relapsing-remitting multiple sclerosis (RR-MS) patients. These cells, showing characteristics of activated cells able to produce pro-inflammatory cytokines, were found to be increased in peripheral blood during relapses and present in high numbers in cerebrospinal fluid. These results suggest that the CD4(+)CD45RO(+)CD49d(high) subpopulation in RR-MS patients includes autoreactive cells and may be target for immunotherapy.

Acute Disease↗
PubMed2000

Peptide T does not ameliorate experimental autoimmune encephalomyelitis (EAE) in Lewis rats.

Peptide T has been shown to inhibit T cell activation and cytokine production and function. Moreover, it has been reported to be a safe treatment in humans. We have studied the ability of peptide T to prevent or ameliorate EAE in Lewis rats. Peptide T was administered subcutaneously at different doses and phases of the disease according to several treatment protocols, but we could not observe a consistent effect of peptide T ameliorating the disease. Lymph node cell proliferation and IL-4 and interferon-gamma production were also studied. We conclude that peptide T neither prevents nor ameliorates EAE in Lewis rats.

Animals↗
PubMed2000

One year follow up study of primary and transitional progressive multiple sclerosis.

OBJECTIVE: To document clinical and magnetic resonance imaging (MRI) characteristics of a large cohort of primary and transitional progressive multiple sclerosis (PP and TP MS) patients over one year. INTRODUCTION: Patients with PP or TP MS have been shown to have low brain T2 and T1 lesion loads and slow rates of new lesion formation with minimal gadolinium enhancement, despite their accumulating disability. Serial evaluation of these patients is needed to elucidate the pathological processes responsible for disease progression and to identify clinical and MRI measures which can monitor these processes in treatment trials. METHOD: Patients, recruited from six European centres, underwent two assessments on the expanded disability status scale (EDSS) and MRI of the brain and spinal cord, 1 year apart. RESULTS: Of the 167 patients studied (137 with PP MS and 30 with TP MS), 41 (25%; 35 PP and six TP) showed a one step increase in the EDSS. The mean number of new brain lesions seen was 0.88 in the PP group and 0.47 in the TP MS group. Both groups demonstrated change in T2 lesion load over the year (p< or =0.002), with median percentage changes of 7.3% in the PP group and 10. 8% in the TP MS group. The PP group also showed a significant change in T1 load (p< 0.001, median change 12.6%). The number of new cord lesions seen was small (mean of 0.14 in the PP group and no new cord lesions in the TP group). Both groups demonstrated a decrease in cord cross sectional area (p< 0.001, median changes; PP 3.8%, TP 4. 9%), but only the PP group showed evidence of significant brain atrophy (p<0.001, 0.95%). CONCLUSION: Although the monitoring of disease progression in this patient group is difficult, this study demonstrates changes in both lesion load and atrophy, which, if shown to correlate with clinical change over a longer time will facilitate therapeutic trial design.

Atrophy↗
PubMed2000

Isolated demyelinating syndromes: comparison of different MR imaging criteria to predict conversion to clinically definite multiple sclerosis.

BACKGROUND AND PURPOSE: Various authors have developed criteria to classify MR imaging findings that suggest the possibility of multiple sclerosis. The purpose of this study was to evaluate and compare the capacity of three sets of MR imaging criteria for predicting the conversion of isolated demyelinating syndromes to clinically definite multiple sclerosis. METHODS: Seventy patients with clinically isolated neurologic symptoms suggestive of multiple sclerosis were prospectively studied with MR imaging. The MR imaging findings were evaluated by two independent neuroradiologists who were blinded to clinical follow-up data. Based on the clinical outcome at follow-up (presence of a second attack that established clinically definite multiple sclerosis), the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the criteria proposed by Paty et al, Fazekas et al, and Barkhof et al were calculated. RESULTS: Clinically definite multiple sclerosis developed in 22 (31%) patients after a mean follow-up time of 28.3 months. The criteria proposed by Paty et al and those proposed by Fazekas et al showed identical results: sensitivity, 86%; specificity, 54%; accuracy, 64%; positive predictive value, 46%; and negative predictive value, 89%. The criteria proposed by Barkhof et al showed the following: sensitivity, 73%; specificity, 73%; accuracy, 73%; positive predictive value, 55%; and negative predictive value, 85%. CONCLUSION: The four dichotomized MR imaging parameters proposed by Barkhof et al are more specific and accurate than the criteria proposed by Paty et al or Fazekas et al for predicting conversion to clinically definite multiple sclerosis.

Adult↗
PubMed2000

[Calcified cerebral metastases. Study of two cases and review of literature].

Although the most frequent cause of intracranial neoplasms are metastases, they very rarely calcify; classic histopathological series have shown the incidence to be approximately 1%. We have found 54 reported cases of intracranial calcified metastasis, the most frequent primary tumour reported being pulmonary adenocarcinoma (13 cases) and adenocarcinoma of gastrointestinal tract and adenocarcinoma of breast (8 cases each). Some reports have shown a longer survival in patients with this kind of image on cerebral scans. We present two patients with intracranial calcified metastasis due to dissemination in both cases of pulmonary adenocarcinomas. The survival under treatment in both patients was similar to that of patients with no calcified metastasis on brain scans. So, facing calcified intracranial lesions, metastatic origin should be considered in the differential diagnosis, pulmonary tumours being the first to be ruled out.

Adenocarcinoma↗
PubMed2000

Diagnostic criteria for primary progressive multiple sclerosis: a position paper.

The unique clinical characteristics of primary progressive multiple sclerosis (PPMS) pose particular diagnostic difficulties, both in excluding other causes of progressive syndromes and in confirming the diagnosis of MS, which is not adequately addressed by current diagnostic criteria. This article presents new diagnostic criteria developed by a group of investigators on the basis of a review of their considerable experience with PPMS. (We conclude that at least 1 year of clinical progression must be documented before a diagnosis of PPMS is made.) Three levels of diagnostic certainty have been defined-definite, probable, and possible--based on clinical findings, abnormal cerebrospinal fluid, abnormalities on magnetic resonance imaging (MRI) of the brain and spinal cord, and evoked potentials. In definite PPMS, evidence of intrathecal synthesis of immunoglobulin G together with one of the following three MRI criteria is required: (1) nine brain lesions, (2) two spinal cord lesions, or (3) four to eight brain lesions and one spinal cord lesion. Preliminary testing of these criteria was carried out on a cohort of 156 patients participating in a European natural history study of PPMS: 64% fulfilled the criteria for definite PPMS, 35% for probable PPMS, and only 1% for possible PPMS. These criteria now require prospective validation in a cohort of newly diagnosed patients and by postmortem examination.

Diagnosis, Differential↗
PubMed1999

[Optic neuritis, brain stem syndromes and myelitis: rapid conversion to multiple sclerosis].

BACKGROUND: To establish the early risk of multiple sclerosis (MS) following isolated demyelinating syndromes. PATIENTS AND METHOD: 36 patients with optic neuritis, 24 with brainstem syndromes, 27 with spinal cord syndromes and 8 patients with a poliregional syndrome were included in a prospective protocol: including clinical data, immunological determinations, oligoclonal bands, visual, somestesic and brainstem evoked potentials and a magnetic resonance imaging (MRI) study. RESULTS: MRI showed the presence of signal abnormalities in 70% of the patients. The conversion rate (CR) was 18.5%. In patients with a normal MRI, CR was 4% compared to 26% in patients with an abnormal MRI (p = 0.05). CONCLUSIONS: The early conversion rate to MS is significantly increased when MRI is abnormal.

Adolescent↗