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X Montalban

Publications and source records attributed to X Montalban.

At least 19 recordsLinked to original sources
PubMed2003

The immune response against herpesvirus is more prominent in the early stages of MS.

OBJECTIVE: To assess antibody levels against human herpesvirus type 6 (HHV-6), Epstein-Barr virus (EBV), and Chlamydia pneumoniae (CP) in serum from individuals in the early and late phase of MS. RESULTS: A strong association was found between anti-HHV-6 immunoglobulin M antibodies and early MS (clinically isolated syndromes at high risk for MS, and short duration active relapsing-remitting MS) when compared with healthy controls and secondary progressive MS. Moreover, in this group of patients, titers for anti-EBV immunoglobulin G were also elevated. The authors found no association between the levels of serum antibodies against CP and MS, nor did they detect the presence of DNA for these pathogens in the serum of patients with MS. Finally, serum from two patients with other inflammatory neurologic diseases also had elevated immunoglobulin M antibodies to HHV-6, indicating that the presence of this antibody is not specific to MS. CONCLUSION: An immune response against herpesviruses such as HHV-6 and EBV is associated with early MS.

Adjuvants, Immunologic↗
PubMed2003

New diagnostic criteria for multiple sclerosis: application in first demyelinating episode.

BACKGROUND: Recently developed diagnostic criteria for MS (McDonald criteria) indicate that in patients with a single demyelinating episode (clinically isolated syndromes [CIS]), evidence for dissemination in space and time, essential for diagnosis, may be provided by MRI. OBJECTIVE: To assess the usefulness of these new criteria in patients with CIS suggestive of MS. METHODS: A total of 139 patients with CIS followed for a median of 3 years underwent brain MRI within 3 months of their first attack and again 12 months later. The number and location of lesions at baseline, the development of new lesions at follow-up, and the results of CSF examination (which, if positive, requires fewer MR abnormalities for diagnosis) were analyzed. The new McDonald criteria (incorporating MRI) were compared to the existing Poser diagnostic criteria and their accuracy was evaluated. RESULTS: At 12 months, 11% had clinically definite MS according to the Poser criteria compared to 37% with the McDonald criteria. Eighty percent of patients fulfilling these new criteria developed a second clinical episode within a mean follow-up of 49 months. The new criteria showed a sensitivity of 74%, specificity of 86%, and accuracy of 80% in predicting conversion to clinically definite MS. CONCLUSION: One year after symptom onset, more than three times as many patients with CIS were diagnosed with MS using new diagnostic criteria incorporating MRI results compared to older criteria. However, the proposed MRI criteria require further prospective studies to optimize sensitivity and specificity.

Adolescent↗
PubMed2003

Metallothionein expression in the central nervous system of multiple sclerosis patients.

Multiple sclerosis (MS) is a major chronic demyelinating and inflammatory disease of the central nervous system (CNS) in which oxidative stress likely plays a pathogenic role in the development of myelin and neuronal damage. Metallothioneins (MTs) are antioxidant proteins induced in the CNS by tissue injury, stress and some neurodegenerative diseases, which have been postulated to play a neuroprotective role. In fact, MT-I+II-deficient mice are more susceptible to developing experimental autoimmune encephalomyelitis (EAE), and treatment of Lewis rats with Zn-MT-II reduces EAE severity. We show here that, as in EAE, MT-I+II proteins were expressed in brain lesions of MS patients. Cells expressing MT-I+II were mainly astrocytes and activated monocytes/macrophages. Interestingly, the levels of MT-I+II were slightly increased in the inactive MS lesions in comparison with the active lesions, suggesting that MTs may be important in disease remission.

Animals↗
PubMed2003

Increased demyelination and axonal damage in metallothionein I+II-deficient mice during experimental autoimmune encephalomyelitis.

Metallothioneins I+II (MT-I+II) are antioxidant, neuroprotective factors. We previously showed that MT-I+II deficiency during experimental autoimmune encephalomyelitis (EAE) leads to increased disease incidence and clinical symptoms. Moreover, the inflammatory response of macrophages and T cells, oxidative stress, and apoptotic cell death during EAE were increased by MT-I+II deficiency. We now show for the first time that demyelination and axonal damage are significantly increased in MT-I+II deficient mice during EAE. Furthermore, oligodendroglial regeneration, growth cone formation, and tissue repair including expression of trophic factors were significantly reduced in MT-I+II-deficient mice during EAE. Accordingly, MT-I+II have protective and regenerative roles in the brain.

Animals↗
PubMed2003

Pharmacogenomic analysis of interferon receptor polymorphisms in multiple sclerosis.

Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system characterized by progressive neurological dysfunction. No curative therapy is currently available, and approximately 80-90% of afflicted individuals are ultimately disabled. Interferon beta (IFNbeta) has been shown to decrease clinical relapses, reduce brain disease activity, and possibly slow progression of disability. However, the overall effect of treatment is partial and a substantial number of patients are considered poor or nonresponders. For this report, we tested the pharmacogenomic effects of eight polymorphisms in the interferon receptor genes (IFNAR1 and IFNAR2) in a group of 147 patients undergoing open-label IFNbeta therapy. Overall, no significant differences in the distribution of responders and nonresponders, classified based on prospectively acquired primary and secondary clinical end points, were observed when stratified by any of the studied IFNAR gene polymorphisms. A trend detected with a single nucleotide polymorphism SNP 16469 (A/T) located at the third intron of the IFNAR1 gene, suggesting modest association with relapse-free status, will require confirmation in an independent data set. In addition, no significant association was observed of any of the IFNAR gene polymorphisms with susceptibility to MS, as studied by a family-based association analysis.

Adolescent↗
PubMed2003

Conversion to multiple sclerosis after a clinically isolated syndrome of the brainstem: cranial magnetic resonance imaging, cerebrospinal fluid and neurophysiological findings.

BACKGROUND AND AIM: Conversion to multiple sclerosis (MS) after optic neuritis and myelitis has been thoroughly studied; however, limited data are available regarding conversion to MS after a clinically isolated syndrome of the brainstem (CISB). The aim of this study was to investigate conversion to MS in patients with CISB. METHODS: Fifty-one patients with CISB were prospectively studied. Cranial magnetic resonance imaging (MRI), determination of oligoclonal bands (OBs) in the cerebrospinal fluid (CSF) and evoked potentials (EPs) were performed. Based on conversion to MS at follow-up, the sensitivity, specificity, accuracy and positive and negative predictive values of these tests were calculated. RESULTS: Clinically definite MS developed in 18 (35%) patients after a mean follow-up of 37 months. Paty's MRI criteria showed a sensitivity of 89%, a specificity of 52% and an accuracy of 65%; Fazekas' criteria showed a sensitivity of 89%, a specificity of 48% and an accuracy of 63%; Barkhof's criteria showed a sensitivity of 78%, a specificity of 61% and an accuracy of 67%. The presence of OBs in the CSF showed a sensitivity of 100%, a specificity of 42% and an accuracy of 63%. No differences for neurophysiological parameters were found between patients who did and those who did not convert to MS. CONCLUSION: Fulfilling Paty's, Fazekas' or Barkhof's MRI criteria and the presence of OBs in the CSF are associated with a higher risk of conversion to MS in patients with CISB. Determination of OBs in the CSF has the greatest sensitivity of all tests. Barkhof's MRI criteria have greater specificity (although less than previously published for mixed cohorts of clinically isolated syndromes) in predicting conversion to MS for CISB than either Paty's or Fazekas' criteria.

Adolescent↗
PubMed2003

Can the Expanded Disability Status Scale be assessed by telephone?

Information from patients who are unable to continue their visits to a study centre may be of major importance for the interpretation of results in multiple sclerosis (MS) clinical trials. To validate a questionnaire based on the Expanded Disability Status Scale (EDSS), patients in five different European centres were assessed independently by pairs of trained EDSS raters, first by telephone interview and a few days later by standardized neurological examination. Seventy women and 40 men with an average age of 43.7 years (range 19-74 years) were included in the study. Mean EDSS score at the last visit was 4.5 (0-9). EDSS assessment by telephone was highly correlated with the EDSS determined by physical examination (Pearson's correlation coefficient = 0.95). An intraclass correlation coefficient (ICC) of 94.8% was found for the total sample; 77.6% and 86%, respectively, for patients with EDSS < 4.5 (n = 46) and > 4.5 (n = 64). Kappa values for full agreement were 0.48; for variation by +0.5 steps and +1.0 steps, 0.79 and 0.90, respectively. Best agreement could be found in higher EDSS scores, where assessment by telephone interview might be needed most. The telephone questionnaire is a valid tool to assess EDSS score in cases where the patient is unable to continue visiting a study centre or in long-term follow-up of trial participants.

Adult↗
PubMed2003

Myelopathy in seronegative Sjögren syndrome and/or primary progressive multiple sclerosis.

OBJECTIVE: The relationship between multiple sclerosis (MS) and Sjögren syndrome (SS) is controversial. Nine patients, previously diagnosed with primary progressive MS (PPMS) and who fulfilled the diagnostic criteria for SS, are described. METHODS: The European classification criteria for SS were used to study nine PPMS patients that complained of sicca complex symptoms. The following tests were performed: Schirmer test, rose bengal staining, salivary scintigraphy, minor salivary gland biopsy and serologic tests (antibodies Ro/SS-A, La/SS-B and antinuclear antibodies). RESULTS: The nine patients met criteria to be diagnosed with SS (at least four criteria). All patients were women with a mean age of 46.6 years at symptom onset. Spastic paraparesis was the presenting symptom in all patients, and spinal cord magnetic resonance imaging (MRI) showed abnormalities in most; anti-Ro and anti-La antibodies were mostly negative. CONCLUSIONS: Some MS patients, predominantly women over 45 years of age, with progressive spastic paraparesis, antiextractable nuclear antigen antibodies (Ro/SS-A or La/SS-B) negative and with abnormalities in spinal cord MRI, may have SS as an additional or alternative diagnosis.

Adult↗
PubMed2002

Treatment with methylprednisolone in relapses of multiple sclerosis patients: immunological evidence of immediate and short-term but not long-lasting effects.

Relapses of multiple sclerosis (MS) are treated commonly with high-dose intravenous methylprednisolone (MP) given over a period of 3-5 days. The mechanisms responsible for the beneficial effects of MP in attacks are not clearly established. It is also controversial whether this treatment may have a long-term effect. Here, peripheral blood samples from relapsing--remitting MS patients in acute relapse were analysed by flow cytometry just before steroid treatment and at different time points after initiation of the therapy. We observed an immediate (day 3) decrease in the percentage of CD4+ lymphocytes, with a relative increase in the memory (CD4+CD45R0+) subpopulation. A longer standing effect of MP on IFN-gamma production, CD54, CCR5, CXCR3 and CD95 (Fas) expression was also observed on CD4+ cells after 1 month of treatment initiation. Six months after the therapy, during clinical remission, no changes due to ivMP therapy were detected. These results support that MP treatment of relapses induces immediate post-treatment and short-term effects on the immune system that could partly account for the clinical and radiological improvement observed in MS patients. However, no conclusion can be drawn as to a possible long-term or even intermediate influence of ivMP treatment on the course of the disease.

Adult↗
PubMed2002

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

This study documents changes in clinical and magnetic resonance imaging (MRI) characteristics in a large cohort of patients with primary and transitional progressive multiple sclerosis (PP and TPMS) over 2 years. Patients with PPMS and TPMS were recruited from six European centres and underwent clinical and MRI examination at three time points: baseline, year one and year two. Of the 190 patients recruited clinical data were available on 125 patients (66%, five centres) and MRI data were available on 113 patients (59%, four centres) at 2 years. Significant increases were seen in T2 load and T1 hypointensity, while brain and cord volume decreased. In PPMS significantly higher lesion loads were found in those who presented with non-cord syndromes when compared to cord presentation and there was a trend to greater brain atrophy in those who deteriorated clinically over the course of the study compared to those who remained stable. Significant cord atrophy was only seen in those with a cord presentation. Measurable changes in MRI parameters can be detected in PPMS patients over a relatively short period of time. MRI quantification is likely to be useful in elucidating disease mechanisms in PPMS and in the execution of clinical trials.

Adult↗
PubMed2002

Expression of chemokine receptors in the different clinical forms of multiple sclerosis.

Chemokines and their receptors are important in the trafficking of peripheral leukocytes into the central nervous system, a major event in the pathogenesis of multiple sderosis (MS). Evidence based on clinical, pathological and magnetic resonance imaging grounds supports some divergence between forms of MS with relapses [relapsing-remitting (RR) and secondary progressive (SP)] and the primary progressive (PP) form. To elucidate whether different pathogenic mechanisms are involved in PPMS, we compared membrane expression of a group of CC and CXC chemokine receptors (CCR1, CCR5, CXCR3, CXCR4) in peripheral blood of 68 MS patients (25 PPMS, 23 SPMS and 20 RRMS) and 26 healthy controls. We found a significant increase in surface expression of CCR5 in CD4+, CD8+, CD19+ and CD14+ cells as well as an increased percentage of CXCR3 and CXCR4 in CD14+ cells in MS patients compared to controls. Increased levels of CXCL10 (IP-10) and CCL5 (RANTES) in cerebrospinal fluid were also observed in a subgroup of MS patients. These results support that chemokines and their receptors are involved in the pathogenesis of MS However, a pattem of chemokine-chemokine receptor expression characteristic of each clinical form of the disease failed to be observed.

Adult↗
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↗