***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background : The cytokine osteopontin ( OPN ) is a potential key player in the immunopathogenesis of multiple sclerosis ( MS ) and a c and i date biomarker for disease activity . Objective : The objective of this study was to examine concentrations of OPN in the cerebrospinal fluid ( CSF ) across the clinical spectrum of MS . Methods : Our research consisted of a cross-sectional study of patients from two r and omized , placebo-controlled trials . Concentrations of OPN and other blood and CSF markers were determined using an enzyme-linked immunosorbent assay ( ELISA ) . Sample s were obtained from untreated patients with exacerbation of clinical ly isolated syndrome ( CIS ) ( n = 25 ) and relapsing – remitting MS ( RRMS ) ( n = 41 ) of whom 48 participated in clinical trials , r and omly allocated to treatment with placebo or methylprednisolone ( MP ) and undergoing repeated sampling after 3 weeks . Furthermore , we obtained CSF and blood sample s from patients with primary progressive MS ( PPMS , n = 9 ) , secondary progressive MS ( SPMS , n = 28 ) and other neurological disorders ( OND , n = 44 ) , and blood sample s from 24 healthy subjects . Results : OPN concentrations were significantly increased in the CSF of patients with CIS ( p = 0.02 ) and RRMS ( p < 0.001 ) in exacerbation compared to patients with OND , and increased levels of OPN were associated with high values of other biomarkers of inflammation . At 3-week follow-up CSF OPN concentrations had decreased significantly from baseline regardless treatment with placebo or MP . Patients with PPMS had increased OPN levels in the CSF ( p = 0.004 ) and high CSF levels of OPN were associated with high degrees of disability . Conclusions : OPN concentration in the CSF is a dynamic indicator of disease activity in RRMS , presumably reflecting ongoing inflammation . Increased CSF OPN concentrations in PPMS may indicate ongoing inflammation even in these patients Background : There is a large unmet need for treatments for patients with progressive multiple sclerosis ( MS ) . Phase 2 studies with cerebrospinal fluid ( CSF ) biomarker outcomes may be well suited for the initial evaluation of efficacious treatments . Objective : To evaluate the effect of monthly oral methylprednisolone pulse treatment on intrathecal inflammation in progressive MS . Methods : In this open-label phase 2A study , 15 primary progressive and 15 secondary progressive MS patients received oral methylprednisolone pulse treatment for 60 weeks . Primary outcome was changes in CSF concentrations of osteopontin . Secondary outcomes were other CSF biomarkers of inflammation , axonal damage and demyelination ; clinical scores ; magnetic resonance imaging measures of disease activity , magnetization transfer ratio ( MTR ) and diffusion tensor imaging ( DTI ) ; motor evoked potentials ; and bone density scans . Results : We found no change in the CSF concentration of osteopontin , but we observed significant improvement in clinical scores , MTR , DTI and some secondary CSF outcome measures . Adverse events were well-known side effects to methylprednisolone . Conclusion : Monthly methylprednisolone pulse treatment was safe , but had no effect on the primary outcome . However , improvements in secondary clinical and MRI outcome measures suggest that this treatment regimen may have a beneficial effect in progressive MS Osteopontin ( OPN ) is a pleiotropic integrin binding protein with functions in cell-mediated immunity , inflammation , tissue repair , and cell survival . Recent studies have shown that OPN may play an important role in the pathogenesis of experimental autoimmune encephalomyelitis and multiple sclerosis ( MS ) . Here , we investigated the plasma levels of OPN in 221 MS patients and 36 healthy controls using an enzyme-linked immunoassay .  The MS group comprised of 71 patients with primary and transitional progressive MS ( PP/TP-MS ) , 35 patients with secondary progressive MS ( SPMS ) , and 115 patients with relapsing-remitting MS (RRMS)[46 patients during clinical remission , 26 patients during relapse , and 43 patients treated with interferon-beta ( IFNbeta ) ]  . Levels of OPN in plasma were elevated in SPMS patients compared with healthy controls , RRMS patients in remission , and PP/TP-MS patients . Patients with RRMS during relapse presented higher OPN levels than patients with RRMS during clinical remission . When MS patients were classified based on progression of neurological disability , an inverse relation between levels of OPN and disability progression was observed only in patients with relapsing MS . In RRMS patients receiving therapy  with IFNbeta , OPN plasma levels were similar to RRMS patients during remission . These findings suggest that OPN is involved in both acute and chronic disease activity , thus exp and ing the role of OPN in MS pathogenesis suggested by previous studies . Furthermore , the different profiles of  OPN levels found in acute relapses and chronic progression and its apparent lack of influence in primary progressive MS phenotypes raise interesting questions on the actual role of OPN in the pathogenesis of MS Objective : Natalizumab inhibits the migration of systemic immune cells to the CNS and may be beneficial in progressive multiple sclerosis ( MS ) . The objective of the study was to examine the effects of natalizumab in progressive MS . Methods : In an open-label phase 2A study , 24 patients with progressive MS were included to receive natalizumab treatment for 60 weeks . Response to natalizumab was assessed in CSF and MRI studies . The primary endpoint was change in CSF osteopontin , a biomarker of intrathecal inflammation , from baseline to week 60 . Results : Seventeen patients completed the study . No new safety issues were encountered . CSF osteopontin decreased by 65 ng/mL ( 95 % confidence interval 34–96 ng/mL ; p = 0.0004 ) from baseline to week 60 in conjunction with decreases in other CSF biomarkers of inflammation , axonal damage , and demyelination . Magnetization transfer ratio increased in both cortical gray and normal-appearing white matter and correlated with decreases in CSF neurofilament light chain . Conclusions : Natalizumab treatment of progressive MS reduces intrathecal inflammation and tissue damage , supporting a beneficial effect of natalizumab treatment in progressive MS and suggesting that systemic inflammation contributes to the pathogenesis . Moreover , the study establishes the feasibility of using CSF biomarkers in proof-of-concept trials , allowing a low number of participants and short study duration . Classification of evidence : This study provides Class IV evidence that in patients with progressive MS  , natalizumab reduces biomarkers of intrathecal inflammation Osteopontin  ( OPN )  was suggested to have a role in the pathophysiology of MS and in bone metabolism . However , we formerly reported increased presence of osteoporosis in MS patients independent of corticosteroid treatment , there is only limited information about the mechanism of bone loss . In this study , we investigated the role of OPN on bone mineral density in MS patients . Thirty-three relapsing-remitting ( RR ) , 12 secondary progressive ( SP ) , and 5 primary progressive ( PP ) MS patients and 30 healthy controls were prospect ively enrolled . Students ' t test , chi-square test , and Pearson correlations were used . The mean OPN level was 155.4+/-81.8 ng/ml in controls , and 15.9+/-36.2 ng/ml in MS patients (p<0.001).No statistical difference was observed among RR , SP and PPMS patients ( p=0.162 ) . No relationship was found between  OPN levels and age at onset of disease ( p=0.830 ) , gender ( p=0.785 ) , MS subtypes ( p=0.330 ) , disease duration ( p=0.744 ) , or EDSS scores (p=0.633).About 34 % of MS patients versus 10.3 % of controls had osteoporosis (p=0.017).Osteopontin levels showed no significant correlation with osteoporosis in controls , but were lower in MS patients with osteoporosis in femur neck ( r=0.85 , p=0.010).The cumulative dose of corticosteroid treatment did not correlate with  OPN levels (p=0.285).In conclusion , our results suggest that OPN may have a role as a shared cytokine in pathogenesis of MS and osteoporosis The patterns of Th1/Th2 cytokines in relapsing-remitting multiple sclerosis were analyzed to evaluate their relevance as biomarkers of therapy response to glatiramer acetate ( GA ) .  Serum interferon-γ ( IFN-γ ) , osteopontin and interleukin (IL)-2 , IL-4 , and IL-10 were measured in 19 relapsing-remitting multiple sclerosis patients treated with GA in a prospect i ve study over 3 years . The quotient ( IL-2 + IFN-γ)/(IL-4 + IL-10 ) was elevated in patients with relapses as compared to relapse-free patients after 12 ( p = 0.04 ) , 24 ( p = 0.02 ) and 36 months ( p = 0.04 ) . Our study indicates that specific patterns of Th1/Th2 cytokines predict the response to GA therapy 
    Output:
    
The result of this study confirms that increased levels of OPN exist in CSF and peripheral blood of MS patients and strengthens the evidence regarding the clinical utility of OPN as a promising and vali date d biomarker for MS