Clinical efficacy issues in the treatment of multiple sclerosis: update of natalizumab

Multiple sclerosis is a frequent neurologic disease, which causes sensory impairment, fatigue, cognitive deficits, imbalance, loss of mobility, spasticity, and bladder and bowel dysfunction. Several new therapies have been introduced in the past decade, but additional drugs are needed to slow disease progression and reduce disability. Natalizumab (NA) is an α4 integrin antagonist, effective in decreasing the development of brain lesions in experimental models and in several studies of patients with MS. Six randomized controlled trials of NA in MS have been published in the last 10 years. Overall, 2,688 relapsing-remitting MS subjects have been enrolled in these studies. Hence, there are already sufficient data to draw some conclusions about the effectiveness of NA in the treatment of MS, although for definitive considerations it would be reasonable to wait for the observational phase IV studies of clinical practice to complete. Moreover, the medical community is concerned with the safety of NA, particularly with the risk of developing progressive multifocal leukoencephalopathy while on NA therapy. From the analyses of the six cases, it seems that the overall risk is around 1/1,000 and could increase with the number of NA infusions

Hopping in the crowd to unveil network topology

We introduce a nonlinear operator to model diffusion on a complex undirected network under crowded conditions. We show that the asymptotic distribution of diffusing agents is a nonlinear function of the nodes' degree and saturates to a constant value for sufficiently large connectivities, at variance with standard diffusion in the absence of excluded-volume effects. Building on this observation, we define and solve an inverse problem, aimed at reconstructing the a priori unknown connectivity distribution. The method gathers all the necessary information by repeating a limited number of independent measurements of the asymptotic density at a single node that can be chosen randomly. The technique is successfully tested against both synthetic and real data, and shown to estimate with great accuracy also the total number of nodes

Lights and Shadows of Cyclophosphamide in the Treatment of Multiple Sclerosis

Cyclophosphamide (cy) is an alkylating agent used to treat malignancies and immune-mediated inflammatory nonmalignant processes. It has been used as a treatment in cases of worsening multiple sclerosis (MS). Cy is currently used for patients whose disease is not controlled by beta-interferon or glatiramer acetate as well as those with rapidly worsening MS. The most commonly used regimens involve outpatient IV pulse therapy given with or without corticosteroids every 4 to 8 weeks. Side effects include nausea, headache, alopecia, pain, male and women infertility, bladder toxicity, and risk of malignancy. Previous studies suggest that cy is effective in patients in the earlier stages of disease, where inflammation predominates over degenerative processes. Given that early inflammatory events appear to correlate with later disability, a major question is whether strong anti-inflammatory drugs, such as cy, will have an impact on later degenerative changes if given early in the disease to halt inflammation

Lights and Shadows of Cyclophosphamide in the Treatment of Multiple Sclerosis

Cyclophosphamide (cy) is an alkylating agent used to treat malignancies and immune-mediated inflammatory nonmalignant processes. It has been used as a treatment in cases of worsening multiple sclerosis (MS). Cy is currently used for patients whose disease is not controlled by beta-interferon or glatiramer acetate as well as those with rapidly worsening MS. The most commonly used regimens involve outpatient IV pulse therapy given with or without corticosteroids every 4 to 8 weeks. Side effects include nausea, headache, alopecia, pain, male and women infertility, bladder toxicity, and risk of malignancy. Previous studies suggest that cy is effective in patients in the earlier stages of disease, where inflammation predominates over degenerative processes. Given that early inflammatory events appear to correlate with later disability, a major question is whether strong anti-inflammatory drugs, such as cy, will have an impact on later degenerative changes if given early in the disease to halt inflammation

Optimal search strategies on complex multi-linked networks

In this paper we consider the problem of optimal search strategies on multi-linked networks, i.e. graphs whose nodes are endowed with several independent sets of links. We focus preliminarily on agents randomly hopping along the links of a graph, with the additional possibility of performing non-local hops to randomly chosen nodes with a given probability. We show that an optimal combination of the two jump rules exists that maximises the efficiency of target search, the optimum reflecting the topology of the network. We then generalize our results to multi-linked networks with an arbitrary number of mutually interfering link sets