Compromised CD4+CD25Hi regulatory T-cell function in patients with relapsing-remitting multiple sclerosis is correlated with a reduced frequency of FOXP3 positive cells and a reduced FOXP3 expression at the single-cell level

CD4(+) CD25(high) regulatory T cells (Tregs) of patients with relapsing-remitting (RR) multiple sclerosis (MS), in contrast to those of patients with secondary progressive (SP) MS, show a reduced suppressive function. In this study, we analysed forkhead box P3 (FOXP3) at the single-cell level in MS patients and controls (healthy individuals and patients with other neurological diseases) by means of intracellular flow cytometry. Our data revealed a reduced number of peripheral blood CD4(+) CD25(high) FOXP3(+) T cells and lower FOXP3 protein expression per cell in RR-MS patients than in SP-MS patients and control individuals, which was correlated with the suppressive capacity of Tregs in these patients. Interestingly, interferon (IFN)-β-treated RR-MS patients showed restored numbers of FOXP3(+) Tregs. Furthermore, a higher percentage of CD4(+) CD25(high) FOXP3(+) Tregs in RR-MS patients, as compared with controls and SP-MS patients, expressed CD103 and CD49d, adhesion molecules involved in T-cell recruitment towards inflamed tissues. This was consistent with a significantly increased number of CD27(+) CD25(high) CD4(+) T cells in the cerebrospinal fluid (CSF), as compared with peripheral blood, in RR-MS patients. Taken together, these data show aberrant FOXP3 expression at the single-cell level correlated with Treg dysfunction in RR-MS patients. Our results also suggest that Tregs accumulate in the CSF of RR-MS patients, in an attempt to down-regulate local inflammation in the central nervous system

Boosting endogenous neuroprotection in multiple sclerosis: the ASsociation of Inosine and Interferon beta in relapsing-remitting Multiple Sclerosis (ASIIMS) trial

Anti-inflammatory drugs are effective on relapses, but neuroprotective agents to prevent disability are still unavailable. Uric acid has neuroprotective effects in experimental models including encephalomyelitis and appears to be involved in multiple sclerosis. Oral administration of inosine, a precursor of uric acid, increases serum uric acid levels and is well tolerated. Our objective was to test the possibility that a combination therapy associating an anti-inflammatory drug (interferon beta) and an endogenous neuroprotective molecule (uric acid) would be more effective than interferon beta alone on the accumulation of disability. Patients with relapsing-remitting multiple sclerosis on interferon beta for at least 6 months were randomized to interferon beta+ inosine or interferon beta+ placebo for 2 years. The dose of inosine was adjusted to maintain serum uric acid levels in the range of asymptomatic hyperuricaemia (<= 10 mg/dl). The primary end points were percentage of patients with progression of disability and time to sustained progression (Kaplan-Meier analysis). The combination of interferon beta and inosine was safe and well tolerated but did not provide any additional benefit on accumulation of disability compared with interferon beta alone. We conclude that endogenous neuroprotective mechanisms recently identified in multiple sclerosis are complex and uric acid does not reflect the entire story

Consensus guidelines on the neurologist's role in the management of neurogenic lower urinary tract dysfunction in multiple sclerosis

<p>Objective: To review current management of neurogenic lower urinary tract dysfunction (NLUTD) in MS patients and give recommendations on the joint role of the neurologist and urologist in NLUTD management.</p><p>Methods: An algorithm for evaluation and referral of MS patients to urologists was created. It is an outcome of discussions about current knowledge, existing guidelines, and key issues during two Belgian consensus meetings attended by neurologists, urologists and other stakeholders involved in MS management. At these meetings, updated information on management of NLUTD in MS was exchanged and the neurologists' opinion on how to integrate this in the other aspects of care in MS patients was explored.</p><p>Results: Short evaluation of NLUTD in MS patients by neurologists and appropriate referral to urologists could accelerate proper diagnosis and treatment. Neurologists can play a central role in the interdisciplinary communication on interactions between disease manifestations of MS and their treatments.</p><p>Conclusion: The coordinating role of neurologists in NLUTD management may considerably improve QoL in MS patients. More research is needed to evaluate outcomes of urological assessments and treatment. (C) 2013 Elsevier B.V. All rights reserved.</p>

Safety and efficacy of natalizumab in Belgian multiple sclerosis patients: subgroup analysis of the natalizumab observational program

Natalizumab (Tysabri(®)) is highly efficacious in controlling disease activity in relapsing multiple sclerosis (MS) patients. As it is one of the more recent therapies for MS, there remains a need for long-term safety and efficacy data of natalizumab in a clinical practice setting. The Tysabri observational program (TOP) is an open-label, multicenter, multinational, prospective observational study, aiming to recruit up to 6,000 patients with relapsing-remitting MS from Europe, Canada and Australia. The objectives of this study are to collect long-term safety and efficacy data on disease activity and disability progression. We report here the interim results of the 563 patients included in TOP between December 2007 and 2012 from Belgium. This patient cohort was older at baseline, had longer disease duration, higher neurological impairment, and a higher baseline annualized relapse rate, when compared to patients included in the pivotal phase III AFFIRM trial. Nevertheless, the efficacy of natalizumab was comparable. The annualized relapse rate on treatment was reduced by 90.70 % (p < 0.0001) with a cumulative probability of relapse of 26.87 % at 24 months. The cumulative probabilities of sustained disability improvement and progression at 24 months were 25.68 and 9.01 %, respectively. There were no new safety concerns over the follow-up period. Two cases of progressive multifocal leukoencephalopathy were diagnosed. Our results are consistent with other observational studies in the post-marketing setting.status: publishe

Safety and efficacy of natalizumab in Belgian multiple sclerosis patients: subgroup analysis of the natalizumab observational program

Natalizumab (Tysabri(®)) is highly efficacious in controlling disease activity in relapsing multiple sclerosis (MS) patients. As it is one of the more recent therapies for MS, there remains a need for long-term safety and efficacy data of natalizumab in a clinical practice setting. The Tysabri observational program (TOP) is an open-label, multicenter, multinational, prospective observational study, aiming to recruit up to 6,000 patients with relapsing-remitting MS from Europe, Canada and Australia. The objectives of this study are to collect long-term safety and efficacy data on disease activity and disability progression. We report here the interim results of the 563 patients included in TOP between December 2007 and 2012 from Belgium. This patient cohort was older at baseline, had longer disease duration, higher neurological impairment, and a higher baseline annualized relapse rate, when compared to patients included in the pivotal phase III AFFIRM trial. Nevertheless, the efficacy of natalizumab was comparable. The annualized relapse rate on treatment was reduced by 90.70 % (p < 0.0001) with a cumulative probability of relapse of 26.87 % at 24 months. The cumulative probabilities of sustained disability improvement and progression at 24 months were 25.68 and 9.01 %, respectively. There were no new safety concerns over the follow-up period. Two cases of progressive multifocal leukoencephalopathy were diagnosed. Our results are consistent with other observational studies in the post-marketing setting