Biomedical subjects

M Trojano

Publications and source records attributed to M Trojano.

At least 37 records · Page 2Linked to original sources

PubMed2000

Interferon beta-1a downregulates TNFalpha-induced intercellular adhesion molecule 1 expression on brain microvascular endothelial cells through a tyrosine kinase-dependent pathway.

TNFalpha (100 U/ml, 24 h) upregulated intercellular adhesion molecule 1 (ICAM1) expression on brain microvascular endothelial cell (BMEC) culture. The tyrosine kinase (TK) inhibitor genestein (100 microgram/ml), the protein kinase C (PKC) inhibitor staurosporin (1 nM), and interferon (IF) beta-1a (1000 U/ml) antagonized TNFalpha effect. When an ineffective dose of IFbeta-1a (100 U/ml) was challenged with ineffective doses of either genestein (10 microgram/ml) or staurosporin (0.1 nM), the combination IFbeta-1a-genestein significantly reduced TNFalpha-induced ICAM1 expression whereas IFbeta-1a-staurosporin did not. These findings indicate that a TK- rather than a PKC-dependent mechanism is involved in the modulation of TNFalpha response by IFbeta-1a on BMECs.

Adjuvants, Immunologic↗

PubMed2000

Inhibition of protein kinase C counteracts TNFalpha-induced intercellular adhesion molecule 1 expression and fluid phase endocytosis on brain microvascular endothelial cells.

TNFalpha (100 U/ml, 24 h) upregulated intercellular adhesion molecule 1 (ICAM1) expression and fluid phase endocytosis (FPE) of horseradish peroxidase on brain microvascular endothelial cell (BMEC) culture. The protein kinase C (PKC) inhibitor staurosporin (0. 5-10 nM) antagonized ICAM1 expression and FPE due to TNFalpha, whereas the protein kinase A inhibitor H89 (0.5-10 nM) did not. These findings indicate that a PKC-dependent mechanism may affect TNFalpha signalling on different barrier properties of BMECs.

Animals↗

PubMed2000

Age at onset in multiple sclerosis.

Age at onset of multiple sclerosis (MS) can vary from childhood to adult life. Many reports have been carried out over the years concerning the role of age at onset in determining the disease outcome. In a sporadic MS population of 1463 patients with homogeneous clinical and demographic features, derived from three Italian neurological centres (Bari, Cagliari and Sassari), we analysed the relative weights of current age and age at onset on disease severity according to the expanded disability status scale (EDSS) score, by fixing the disease duration. The results of present study demonstrate that clinical disability in MS is influenced by the patient's age (p < 0.01) and not by the age at onset. Therefore, these data do not confirm the hypothesis that an early age at onset should be considered a favourable prognostic factor of the disease outcome.

Adolescent↗

PubMed2000

An attempt of identifying MS-associated loci as a follow-up of a genomic linkage study in the Italian population.

Subsequent to a genomic linkage study on Sardinian and Continental Italian families, we considered the possibility that some of the tested microsatellite markers showed association to MS. Markers selected on the basis of the data obtained in the original set of 70 multiplex families were tested for MS association in an additional set of 154 simplex families. A limited set of markers were further tested on an additional set of 100 simplex families. The results indicate the presence of a putative MS gene in 19q13.13.

Alleles↗

PubMed2000

Effects of rIFN-beta-1b on serum circulating ICAM-1 in relapsing remitting multiple sclerosis and on the membrane-bound ICAM-1 expression on brain microvascular endothelial cells.

rIFN-beta reduces the frequency of the gadolinium-enhancing (Gd+) magnetic resonance imaging (MRI) lesions in relapsing remitting (RR) MS. Its mechanism of action on improving the integrity of the blood-brain barrier (BBB) remains unclear. We investigated the effect of rIFN-beta-1b on the soluble intercellular adhesion molecule-1 (sICAM-1) serum levels (ELISA) in 36 RR MS patients receiving treatment with rIFN-beta for 1 year, and also the TNF-alpha - induced membrane-bound ICAM-1 (mICAM-1) expression on cultured rat brain microvascular endothelial cells (BMECs). In vivo data showed that sICAM-1 serum levels at baseline significantly increased (P<0.01) in 12 months of rIFN-beta-1b treatment. The increase paralleled a clinical and MRI improvement. In the second semester of the treatment the integrated area under the curve of Expanded Disability Status Score normalised to entry baseline (DeltaEDSS AUC) was significantly (P<0.05) smaller than in the first semester. The percentage of patients with Gd+MRI decreased significantly (P<0.05) in the first (33%) and second (29%) semesters of treatment compared to baseline (62%). In vitro experiments showed that the incubation of BMEC monolayer with 100 u/ml of TNF-alpha for 24 h significantly (P<0.05) increased mICAM-1 expression, whereas 2000 u/ml of rIFN-beta-1b for 72 h did not modify the baseline levels. The incubation of BMEC with 2000 u/ml of rIFN-beta-1b for 48 h followed by combined IFN-beta-1b and TNF-alpha for 24 h significantly (P<0.05) downregulated TNF-alpha-induced mICAM-1 expression. These results suggest that the effect of rIFN-beta-1b on the BBB may be mediated by changes in both sICAM-1 serum levels and mICAM-1 BMEC expression.

Adjuvants, Immunologic↗

PubMed1999

Changes of serum sICAM-1 and MMP-9 induced by rIFNbeta-1b treatment in relapsing-remitting MS.

OBJECTIVE: To correlate changes in serum levels of intercellular adhesion molecule-1 (sICAM-1) and matrix metalloproteinases (MMP) with clinical and MRI evidence of disease activity in MS patients receiving treatment with interferon-beta (rIFNbeta)-1b. BACKGROUND: rIFNbeta reduces the frequency of gadolinium-enhancing (Gd+) MRI in relapsing-remitting MS (RRMS). Its mechanism of action on improving the integrity of the blood-brain barrier remains unclear. METHODS: sICAM-1 and MMP-9 and MMP-2 serum levels were longitudinally (24 months) investigated (ELISA; zymography) in correlation with the modifications of the integrated area under the curve of Expanded Disability Status Scale scores normalized to entry baseline (deltaEDSS AUC) and of GD+ MRI scans, and with neutralizing antibodies (NAB) to rIFNbeta-1b production (MxA) in 36 RRMS patients. RESULTS: During the first 12 months of treatment, levels of sICAM-1 increased and MMP-9 decreased significantly. After 12 months, levels returned toward baseline. Levels of sICAM-1 and MMP-9 were significantly negatively correlated. MMP-2 levels did not change significantly during the same period. During the second semester of the study, deltaEDSS AUC was significantly reduced. The percentage of patients with Gd+ MRI decreased significantly in the first (33%), second (29%), third (20%), and fourth (28%) semesters of treatment compared to baseline (62%). The NAB+ patients (14%) tended to have lower sICAM-1 levels at the ninth month; a higher MMP-9 activity at the sixth, 12th, and 18th months; and a greater deltaEDSS AUC in the third semester of treatment in comparison with the NAB- patients. CONCLUSIONS: These results show that rIFNbeta-1b therapy increases sICAM-1 serum levels and reduces serum MMP-9 activity.

Adjuvants, Immunologic↗

PubMed1999

Comparison of clinical and demographic features between affected pairs of Italian multiple sclerosis multiplex families; relation to tumour necrosis factor genomic polymorphisms.

We conducted a comparative analysis of clinical and demographic findings between pairs of relatives (36 sibling and 9 parent/child), concordant for Multiple Sclerosis (MS), from 40 MS Italian Multiplex families. A genetic TNF (alpha and beta) loci typing in 51 affected and 69 healthy relatives belonging to 25 of these families was also performed. The sib pairs resulted significantly concordant for age at onset (r=0.414, P<0.013), Progression Index (r=0.34, P<0.05) and sensory symptoms at onset (k=0.37), and significantly not concordant for sex (k=-0.37), whereas no concordance was found for year at onset and disease course. The only significant result in the small group of parent/child pairs was that parents developed MS at an age of 18.74 years significantly (P=0.020) greater than their children. Genomic analysis identified 13 variants of TNF-a alleles, 7 of TNF-b, 6 of TNF-d and 3 of TNF-e. No differences in the frequencies of the various TNF alleles were observed between affected and healthy relatives. The two-point lod-score analysis of the TNF locus showed not significant or negative results for the TNFalpha loci and slightly positive results (Zmax=0.4 at theta=0.2 cM) for the TNFbeta-b locus in the lowest penetrance dominant model. The Sib pair analysis, using combined TNFalpha and TNFbeta haplotypes, demonstrated a TNF allele sharing between affected sib-pairs which did not exceed the expected 50%. These results suggest that genetic factors may partially influence the disease onset and the progression rate in sibling pairs. A recall bias and/or an 'anticipation phenomenon' could explain the development of MS at an older age in parents than in their children. In this small-sized cohort of MS Italian families no significant associations were confirmed between TNF polymorphism and MS.

Adult↗

PubMed1999

Linkage analysis of multiple sclerosis with candidate region markers in Sardinian and Continental Italian families.

Previous genome screens in multiple sclerosis have shown some evidence of linkage in scattered chromosomal regions. Although in no case the evidence of each single study was compelling and although in general the linkage 'peaks' of the different studies did not coincide, some regions can be considered likely candidates for the presence of MS risk genes because of the clustering of MLS scores and homology with eae loci. We performed a linkage analysis of markers in these regions and of intragenic markers of some individual candidate genes (HLA-DRB1, CTLA-4, IL9, APOE, BCL2, TNFR2). For the first time, Southern European populations were targeted, namely Continental Italians and Sardinians. A total of 69 multiplex families were typed for 67 markers by a semi-automatic fluorescence-based assay. Results were analysed for linkage by two non-parametric tests: GENEHUNTER and SimIBD. In general, the linkage scores obtained were low, confirming the conclusion that no gene is playing a major role in the disease. However, some markers, in 2p11, 3q21.1, 7p15.2 and 22q13.1 stood out as promising since they showed higher scores with one or the other test. This stimulates further association analysis of a large number of simplex families from the same populations.

Genetic Linkage↗

PubMed1998

ICAM 1 expression and fluid phase endocytosis of cultured brain microvascular endothelial cells following exposure to interferon beta-1a and TNFalpha.

We have studied the effect of interferon (IF) beta-1a on the basal and TNFalpha-induced intercellular adhesion molecule 1 (ICAM 1) expression and fluid phase endocytosis (FPE) of horseradish peroxidase in cultured rat brain microvascular endothelial cells. Neither basal ICAM 1 expression nor basal FPE were significantly affected by 24-72 h exposure to 1000 U/ml IFbeta-1a. ICAM 1 induction and FPE enhancement caused by 100 U/ml TNFalpha for 24 h was not influenced by simultaneous administration of 1000 U/ml IFbeta-1a. Treatment of cultures with IFbeta-1a for 48 h followed by 24-h coincubation with TNFalpha (100 U/ml) and IFbeta-1a (1000 U/ml) resulted in significant downregulation of TNFalpha-induced ICAM 1 expression and FPE. Downregulation of TNFalpha-induced ICAM 1 expression was not observed when combined treatment with TNFalpha (100 U/ml) and IFbeta-1a (1000 U/ml) for 24 h was followed by 48 h exposure to IFbeta-1a. We concluded that the blood-brain barrier endothelium may be a target of IFbeta-1a. Further, these in vitro findings may correlate with the results of recent clinical trials indicating that chronic treatment of relapsing remitting multiple sclerosis with IFbeta-1a prevents both clinical exacerbations and the appearance on Magnetic Resonance Imaging of new lesions enhanced by gadolinium which is taken up by increased transendothelial fluid phase vesicular transport.

Animals↗

PubMed1998

Soluble intercellular adhesion molecule-I (sICAM-I) in serum and cerebrospinal fluid of demyelinating diseases of the central and peripheral nervous system.

Serum and cerebrospinal fluid (CSF) soluble intercellular adhesion molecule-I (ICAM-I) levels were evaluated (ELISA) in 22 untreated and 13 corticosteroid-treated active relapsing remitting (RR) Multiple Sclerosis (MS), in 10 untreated and 10 corticosteroid-treated Guillain-Barré syndrome (GBS) and in 17 non-inflammatory neurological diseases (NIND). Twenty-eight clinically inactive RR MS were assayed for serum sICAM-I before and after 3 months treatment of 8 MIU rIFN beta-Ib taken s.c. every other day. High sICAM-I serum levels above the NIND values were found in untreated clinically active MS and in untreated GBS (P < 0.05) but not in the untreated clinically inactive MS group. The active MS group showed significantly (P = 0.0001) higher sICAM-I serum levels if compared to the inactive group. Corticosteroid-treated active MS and GBS patients showed lower (P < 0.05) serum sICAM-I levels than the corresponding untreated groups. Serum sICAM-I levels after 3 months of rIFN beta-Ib treatment (P < 0.0001, paired t-test) resulted increased compared to pretreatment values in MS. The mean values of CSF/serum sICAM-I:CSF/serum Albumin ratios (sICAM-I Index) in active untreated MS patients were higher compared to NIND (P < 0.005) and to corticosteroid-treated MS group (P = 0.01). sICAM Index values in GBS did not differ from those in NIND. The results seem to suggest potential roles for serum sICAM-I in downregulating the ongoing inflammatory response at the blood-brain barrier level and for CSF sICAM-I in the maintenance of a central nervous system local immune response.

Adrenal Cortex Hormones↗

PubMed1998

Serum soluble intercellular adhesion molecule-I in MS: relation to clinical and Gd-MRI activity and to rIFN beta-Ib treatment.

The validity of serum sICAM-I levels to assess Multiple Sclerosis (MS) activity was evaluated in 49 untreated definite relapsing-remitting (RR) patients. sICAM-I levels were significantly (P = 0.0009) higher in the 'clinically active' group (No 22) than in the 'clinically inactive' (No 27), whereas no different values were found between patients with Gd-enhancing lesions at MRI (Gd-positive) (No 32) and patients without such lesions (Gd-negative) (No 17) independently of their clinical activity. Among the 'clinically active' MS, the Gd-positive (No 16) subgroup showed significant (P < 0.05) lower sICAM-I levels when compared to the Gd-negative (No 6) subgroup, but higher (P = 0.009) than those of the 'clinically inactive Gd-positive' (No 16) patients. The sICAM-I levels did not differ between the two 'clinically inactive' subgroups Gd-positive (No 16) and Gd-negative (No 11). Finally the clinically active Gd-negative (No 6) showed sICAM-I levels higher (P = 0.002) than the clinically inactive Gd-negative (No 11). The specificity of high serum sICAM-I levels (above M +/- 2 s.d. of control values) to assess the disease activity in MS resulted higher (100%) using clinical than Gd-MRI activity (76%) as gold standard. The changes induced by 1 year recombinant Interferon-beta-Ib (rIFN beta-Ib) treatment on sICAM-I serum levels were also longitudinally investigated in 36 of the 49 RR MS. sICAM-I levels at baseline significantly increased in the first 2 months (baseline vs 1st month P < 0.0001 and 1st vs 2nd month P = 0.02), persisted at high levels without any significant change after 3 months, showed a temporary decrease at 6 months, then significantly increased again at 9 and 12 months. Fourteen patients experienced relapses, with a total of 20 relapses, during the whole treatment duration. The mean relapse/rate and the frequency of patients with Gd-positive MRI scans resulted significantly higher in the first semester compared to the second semester of treatment. This study adds further insights into the validity of serum sICAM-I to assess disease activity in MS and on the immunomodulatory properties of rIFN beta-Ib.

Adjuvants, Immunologic↗

PubMed1997

Randomized placebo-controlled trial of mitoxantrone in relapsing-remitting multiple sclerosis: 24-month clinical and MRI outcome.

We designed a randomized, placebo-controlled, multicentre trial involving 51 relapsing-remitting multiple sclerosis patients to determine the clinical efficacy of mitoxantrone treatment over 2 years. Patients were allocated either to the mitoxantrone group (27 patients receiving I.V. infusion of mitoxantrone every month for 1 year at the dosage of 8 mg/m2) or to the placebo group (24 patients, receiving I.V. infusion of saline every month for 1 year) using a centralized randomization system. Disability at entry and at 12-24 months was evaluated by four blinded neurologists trained in the application of the Kurtzke Expanded Disability Scale (EDSS). In addition, the number and clinical characteristics of the exacerbations over the 24 months were recorded by the local investigators. MRI, at 0, 12 and 24 months, was performed with a 0.2 T permanent unit. MRI data were analysed by two blinded neuroradiologists. All patients underwent a clinical evaluation. A statistically significant difference in the mean number of exacerbations was observed between the mitoxantrone group and placebo group both during the 1st and the 2nd year. Although there was no statistically significant benefit in terms of mean EDSS progression over 2 years, the proportion of patients with confirmed progression of the disease, as measured by a one point increase on the EDSS scale, was significantly reduced at the 2nd year evaluation in the mitoxantrone group. Forty-two (23 mitoxantrone, 19 placebo) patients underwent all MRI examinations during the 24-month period. We observed a trend towards a reduction in the number of new lesions on T2-weighted images in the mitoxantrone group. Our study suggests that mitoxantrone might be effective in reducing disease activity, both by decreasing the mean number of exacerbations and by slowing the clinical progression sustained by most patients after 1 year from the end of treatment.

Adjuvants, Immunologic↗

PubMed1996

Serum IgG to brain microvascular endothelial cells in multiple sclerosis.

Serum IgG to brain microvascular endothelial cells (BMECs) were assessed in the sera from 50 patients with definite multiple sclerosis, 24 patients with other inflammatory and non-inflammatory neurological diseases and 30 healthy individuals. Standard indirect immunofluorescence on BMEC culture was used as the bioassay system. Positive immunostaining was found in the sera (1:5 to 1:50 dilution) from 0/15 inactive relapsing remitting (RR), 12/16 active RR (p = 0.0001), 1/8 relapsing progressive (RP) and 0/11 primary progressive (PP) patients. No specific binding was detected when sera from neurologic and healthy controls were used. The specificity of the immune reaction for brain endothelium was established by the absence of staining on human umbilical vein endothelial cell and brain pericyte cultures. Gadolinium (Gd)-enhanced magnetic resonance imaging of the brain and spinal cord was performed in 36 MS patients within a 10-day interval from serum collection. Anti-brain endothelium antibodies were found in 9/12 patients with, and in 1/24 patients without Gd-enhanced lesions (p = 0.00002). Regardless of a pathogenetic role in the blood-brain barrier breakdown, serum IgG to BMECs may be a marker of disease activity in RR and RP MS and a factor differentiating RR/RP and PP MS.

Adult↗

PubMed1996

High resolution proton MR spectroscopy of cerebrospinal fluid in MS patients. Comparison with biochemical changes in demyelinating plaques.

Proton magnetic spectroscopy (1H-MRS) investigation was performed on CSF samples of patients with neurological inflammatory diseases including 52 cases of multiple sclerosis (MS). 12 acute idiopathic polyneuropathies, 20 acute meningitides (10 viral and 10 bacterial). Spectra were compared with those acquired in 18 neurological controls. High CSF lactate levels were found in MS patients during clinical exacerbation of relapsing-remitting course (p = 0.036 vs neurological controls). In MS patients with MRI evidence of Gd-enhanced plaques CSF lactate was higher than in patients with MRI inactive plaques (p = 0.017). CSF lactate positivity correlated with number of CSF mononuclear cells in MS patients with clinical activity (p = 0.05) as well as in MS patients with MRI enhancement (p = 0.003). A comparative 1H-MRS investigation in vivo on localized demyelinating areas confirmed an elevated lactate signal in Gd-enhanced (61%) more frequently than in unenhanced (22%) plaques (p = 0.03). MS patients with high lactate signal in active plaques showed high lactate levels in CSF. Increased CSF lactate was found also in patients with acute meningitis and idiopathic polyneuropathy. These data suggest that changes in lactate levels may depend on anaerobic glycolytic metabolism in activated leukocytes during inflammatory diseases. A decrease of CSF formulate levels was found in MS patients during active and inactive clinical phase (p = 0.037, p=0.05 vs neurological controls respectively). Formate changes might be related to a disorder of choline-glycine cycle in MS. 1H-MRS in vivo showed significant increase of choline in acute plaques, whereas a decrease of N-acetyl aspartate was found in chronic plaques; these metabolites are undetectable in CSF. CSF glucose levels were lower in bacterial than in viral meningitis (p = 0.014) and in neurological controls (p = 0.05). These observations suggest that 1H-MRS may be able to detect CSF metabolic impairment in neurological inflammatory diseases. In MS some CSF findings reflect metabolic changes occurring in brain demyelinating areas, and they could be useful foe evaluation of disease activity in different stages of disease evolution.

Adolescent↗

PubMed1996

Soluble intercellular adhesion molecule-1 in serum and cerebrospinal fluid of clinically active relapsing-remitting multiple sclerosis: correlation with Gd-DTPA magnetic resonance imaging-enhancement and cerebrospinal fluid findings.

We measured soluble intercellular adhesion molecule-1 (sICAM-1) in the serum and cerebrospinal fluid (CSF) of 35 clinically active relapsing-remitting (RR) multiple sclerosis (MS) patients who underwent both lumbar puncture and gadopentetate dimeglumine (Gd-DTPA)-enhanced MRI within an interval of 1 week, and of 30 neurological controls of whom 17 had noninflammatory neurologic diseases (NIND), 8 bacterial meningitis (BM), and 5 AIDS dementia complex (ADC). Thirteen of the MS patients assumed corticosteroids at the time of the study. While sICAM-1 serum levels were highest in the BM group (p < 0.005), untreated MS patients showed levels higher (p < 0.05) than treated MS and NIND, but similar to ADC. Moreover, the untreated MS group had CSF/serum sICAM-1:CSF/serum albumin (sICAM-1 index) values higher than the treated group (p < 0.01), NIND (p < 0.005), and BM (p < 0.05); high sICAM-1 index was found also in ADC. Untreated MS patients with one or more Gd-DTPA-enhancing MRI lesions (Gd-positive) had higher mean values of CSF/serum albumin ratio (QAlbumin) and CSF mononuclear cells compared to patients without such lesions (Gd-negative). In the untreated Gd-negative patients, sICAM-1 serum levels were higher (p < 0.05) than those in Gd-positive patients. In the latter group, there were positive correlations between the number of CSF mononuclear cells and both IgG (p < 0.01) and sICAM-1 indices (p < 0.05), between QAlbumin and QsICAM-1 (p < 0.005) and between Qalbumin and the Expanded Disability Status Scale score (p = 0.05). There were no significant correlations in the Gd-negative group. These results suggest that sICAM-1 index can be a better marker of intrathecal sICAM-1 synthesis than CSF levels and provide additional insights, in vivo, into the blood-brain barrier mechanisms underlying MRI Gd-enhancement in clinically active RR MS.

Adolescent↗

PubMed1995

Multivariate analysis of predictive factors of multiple sclerosis course with a validated method to assess clinical events.

The clinical data of 309 patients with definite multiple sclerosis were recorded in the European data base for multiple sclerosis (EDMUS) to determine the prognostic significance of several demographic and clinical variables. An interview with closed questions structured according to standardised criteria of disease phases and courses was used to assess the clinical course. The reliability was evaluated by four trained neurologists in a sample of 33 patients with multiple sclerosis. Both the within and between rater agreement on data collection was fair to high for the historical variables (K = 0.33-1). Between rater agreement was more variable for the evaluation of 12 different EDMUS event categories (K = 0.3-0.95). The predictive model for the time to reach a secondary progression showed that an age at onset older than 25 (p = 0.006) and an event at onset followed by disability > or = 3 on the Kurtzke expanded disability status scale (EDSS; p = 0.004) were the most unfavourable clinical variables in 249 patients with relapsing remitting (180) or relapsing progressive (69) courses. In the 69 patients with relapsing progressive disease, the time to reach severe disability (EDSS > or = 6) was negatively influenced by a first interval between attacks shorter than one year, a number of bouts with EDSS > 2 in the first two years of the disease, and involvement of the pyramidal system at onset (p < 0.05). In 60 patients with chronic progressive disease this outcome was negatively influenced by pyramidal, brainstem, and sensory involvement at onset (p < 0.01).

Adult↗

PubMed1994

A controlled trial of mitoxantrone in multiple sclerosis: serial MRI evaluation at one year.

We present the results of a randomized double-blinded placebo controlled, multicenter trial, of low-dose mitoxantrone (MX), after one year, in 25 patients with relapsing-remitting multiple sclerosis, who had serial enhanced magnetic resonance imaging (MRI). Treatment groups were balanced for age, gender, duration of illness and neurological disability. Five of the 13 MX patients and 10 of the 12 placebo patients had exacerbations during treatment (p < 0.02). The mean change in the extended disability status scale was not significantly different between the MX and placebo treatment groups. Serial Gadolinium-DTPA enhanced MRI detected no significant difference between the MX treated and placebo groups in the mean total number of new, enlarging, or Gadolinium-DTPA enhancing lesions; there was a trend toward a reduction of new, enlarging and Gadolinium-DTPA enhancing lesions in MX patients. Despite this ameliorating effect, the results indicate that serial Gadolinium-DTPA enhanced MRI, performed over one year in a limited number of patients, could not provide conclusive evidence for a role of MX therapy in relapsing-remitting multiple sclerosis.

Adolescent↗

PubMed1992

Blood-brain barrier changes in multiple sclerosis.

We review the salient published data suggesting blood-brain barrier (BBB) damage in multiple sclerosis (MS). We focus attention specifically on: 1) the cerebral microvessel involvement in demyelination plaques, 2) the presence of dynamic changes in BBB permeability depending on the phase of the disease course, 3) the primary role of cerebral endothelial cells in the development of the intracerebral immune response.

Blood-Brain Barrier↗