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Primary Progressive (primary + progressive)

Distribution by Scientific Domains
Medical Sciences100%

Terms modified by Primary Progressive

  • primary progressive aphasia
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  • primary progressive multiple sclerosis
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    Selected Abstracts

    Rituximab in patients with primary progressive multiple sclerosis: Results of a randomized double-blind placebo-controlled multicenter trial,

    ANNALS OF NEUROLOGY, Issue 4 2009
    Kathleen Hawker MD
    Objective Rituximab, a monoclonal antibody selectively depleting CD20+ B cells, has demonstrated efficacy in reducing disease activity in relapsing-remitting multiple sclerosis (MS). We evaluated rituximab in adults with primary progressive MS (PPMS) through 96 weeks and safety through 122 weeks. Methods Using 2:1 randomization, 439 PPMS patients received two 1,000mg intravenous rituximab or placebo infusions every 24 weeks, through 96 weeks (4 courses). The primary endpoint was time to confirmed disease progression (CDP), a prespecified increase in Expanded Disability Status Scale sustained for 12 weeks. Secondary endpoints were change from baseline to week 96 in T2 lesion volume and total brain volume on magnetic resonance imaging scans. Results Differences in time to CDP between rituximab and placebo did not reach significance (96-week rates: 38.5% placebo, 30.2% rituximab; p = 0.14). From baseline to week 96, rituximab patients had less (p < 0.001) increase in T2 lesion volume; brain volume change was similar (p = 0.62) to placebo. Subgroup analysis showed time to CDP was delayed in rituximab-treated patients aged <51 years (hazard ratio [HR] = 0.52; p = 0.010), those with gadolinium-enhancing lesions (HR = 0.41; p = 0.007), and those aged <51 years with gadolinium-enhancing lesions (HR = 0.33; p = 0.009) compared with placebo. Adverse events were comparable between groups; 16.1% of rituximab and 13.6% of placebo patients reported serious events. Serious infections occurred in 4.5% of rituximab and <1.0% of placebo patients. Infusion-related events, predominantly mild to moderate, were more common with rituximab during the first course, and decreased to rates comparable to placebo on successive courses. Interpretation Although time to CDP between groups was not significant, overall subgroup analyses suggest selective B-cell depletion may affect disease progression in younger patients, particularly those with inflammatory lesions. Ann Neurol 2009;66:460,471 [source]

    Abnormal Endothelial Tight Junctions in Active Lesions and Normal-appearing White Matter in Multiple Sclerosis

    BRAIN PATHOLOGY, Issue 2 2002
    Jonnie Plumb
    Blood-brain barrier (BBB) breakdown, demonstrable in vivo by enhanced MRI is characteristic of new and expanding inflammatory lesions in relapsing-remitting and chronic progressive multiple sclerosis (MS). Subtle leakage may also occur in primary progressive MS. However, the anatomical route(s) of BBB leakage have not been demonstrated. We investigated the possible involvement of interendothelial tight junctions (TJ) by examining the expression of TJ proteins (occludin and ZO-1) in blood vessels in active MS lesions from 8 cases of MS and in normal-appearing white (NAWM) matter from 6 cases. Blood vessels (10,50 per frozen section) were scanned using confocal laser scanning microscopy to acquire datasets for analysis. TJ abnormalities manifested as beading, interruption, absence or diffuse cytoplasmic localization of fluorescence, or separation of junctions (putative opening) were frequent (affecting 40% of vessels) in oil-red-O-positive active plaques but less frequent in NAWM (15%), and in normal (<2%) and neurological controls (6%). Putatively "open" junctions were seen in vessels in active lesions and in microscopically inflamed vessels in NAWM. Dual fluorescence revealed abnormal TJs in vessels with pre-mortem serum protein leakage. Abnormal or open TJs, associated with inflammation may contribute to BBB leakage in enhancing MRI lesions and may also be involved in subtle leakage in non-enhancing focal and diffuse lesions in NAWM. BBB disruption due to tight junctional pathology should be regarded as a significant form of tissue injury in MS, alongside demyelination and axonopathy. [source]

    Increased cerebrospinal fluid chitotriosidase index in patients with multiple sclerosis

    ACTA NEUROLOGICA SCANDINAVICA, Issue 5 2010
    M. M. Verbeek
    Verbeek MM, Notting EA, Faas B, Claessens-Linskens R, Jongen PJH. Increased cerebrospinal fluid chitotriosidase index in patients with multiple sclerosis. Acta Neurol Scand: 2010: 121: 309,314. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective,,, To investigate chitotriosidase (CTTS) activity in serum and cerebrospinal fluid (CSF) in multiple sclerosis (MS) patients in relation to disease course and CSF markers for immune activation or inflammation. Materials and methods,,, We studied 80 patients with relapsing,remitting MS (RRMS), 24 with secondary progressive MS (SPMS), 20 with primary progressive MS (PPMS) and 29 patients with other neurological disorders (OND). We measured CTTS activity and studied the correlation with CSF mononuclear cell count (MNC) and intrathecal IgG production. Results,,, CTTS activity was significantly higher in CSF, but not in serum, from the total MS group compared with OND and controls. In RRMS and SPMS CTTS, index was increased compared with controls (RRMS, 0.10 ± 0.21; SPMS, 0.10 ± 0.15; controls, 0.021 ± 0.020), but not in PPMS (0.061 ± 0.052). CTTS index was higher in MS patients with elevated MNC or CSF-restricted oligoclonal IgG bands than in MS patients without these CSF findings. Conclusions,,, CTTS index is elevated in RRMS and SPMS. The CTTS index is related to CSF markers of inflammation or immune activation. [source]

    Multiple sclerosis in a family on the Faroe Islands

    ACTA NEUROLOGICA SCANDINAVICA, Issue 1 2010
    S. Binzer
    Background,,, John Kurtzke has proposed that multiple sclerosis (MS) on the Faroe Islands occurred as a result of the spread of a transmittable agent brought to the country during World War II. Aim,,, Kurtzke's theory has been opposed earlier and in this study, we present a family from the Faroe Islands containing a total of 14 family members with MS which show further inconsistencies with the theory. The present study is to our knowledge, the first description of familial incidences of MS on the Faroe Islands. Methods,,, Medical histories were gathered from 12 family members and 6 of the 8 living MS cases were human leukocyte antigen (HLA)-typed. Results,,, Seven family members had primary progressive MS (PPMS), while five had relapsing remitting MS. The HLA-DR15 allele was carried by the three cases with the most aggressive form of MS and they shared a common haplotypes. The HLA types carried by the remaining cases varied. Conclusion,,, This research questions Kurtzke's theory as three of the cases do not conform to the epidemic cohorts described. Furthermore, there appears to be a higher than usual prevalence of PPMS. The high degree of heterogeneity of the HLA types carried indicates that HLA alleles do not independently explain the risk of developing MS. [source]

    Change in sex ratio, disease course and age at diagnosis in Oslo MS patients through seven decades

    ACTA NEUROLOGICA SCANDINAVICA, Issue 2009
    E. G. Celius
    Objectives , To study changes in sex ratio, disease course, time from onset to diagnosis and age at diagnosis by year of birth in a well-defined population of multiple sclerosis (MS) patients. Materials and methods , Based on the Oslo MS Registry patients born from 1910 to 1980 with residence in Oslo at time of diagnosis were studied. Data were analyzed by 10-year intervals based on year of birth. Results , The female to male ratio increased significantly from 1.48 to 2.30 through seven decades. Also, the ratio of initial relapsing,remitting (RR-MS) to primary progressive (PP-MS) disease course increased significantly from 1.93 to 16.00. The time from onset to diagnosis and the mean age at diagnosis declined significantly during the same period. Conclusions , This study shows that there has been a change in MS sex ratio, disease course and age at diagnosis through a period of seven decades, suggesting an environmental factor mainly affecting women at a younger age and causing a RR-MS disease course. [source]