16 Mar 10

Absence of Epstein-Barr virus in the brain and CSF of patients with multiple sclerosis
Neurology. 2010 Mar 10

The Epstein-Barr virus (EBV) has been largely associated with the risk of MS. The authors of this study aimed to investigate whether the presence of a possible latent or active EBV infection in the central nervous system (CNS) of people with MS could be actually playing a role in the development of the disease. After studying active brain MS plaques and different types of immune cells located in the CNS of people with MS, the authors found no evidence of latent or active EBV infection. Nor did they find specific anti-EBV antibody response within the CNS of people with MS. More investigations are needed to link the results of this study with the considerable number of studies that associate EBV infection with an increased risk of MS.
Source abstract

16 Mar 10

Elevated Epstein-Barr virus-encoded nuclear antigen-1 immune responses predict conversion to multiple sclerosis
Ann Neurol. 2009 Oct 13;67(2):159-169

Currently available markers for developing MS after a first inflammatory-demyelinating episode of the central nervous system, and markers for disability progression are still far from satisfactory. The authors of this study found that the concentration, in peripheral blood, of a specific protein produced after an infection by the Epstein-Barr virus was higher in people who had experienced a first attack compared to controls. Moreover, they found that people with higher concentrations of this protein, related to EBV, had a higher risk of developing MS and experiencing a worse clinical outcome over the following years. Interestingly, the other proteins studied, related to EBV and other viruses, did not show this capacity. Therefore, the authors propose that this protein be considered as a possible marker for the development of the disease and for disability progression.
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16 Mar 10

Human leukocyte antigen-DR15, low infant sibling exposure and multiple sclerosis: gene-environment interaction
Ann Neurol. 2009 Sep 4;67(2):261-265

MS is a complex disease where both environmental and genetic factors play a role in its development. In this elegant study, the authors demonstrated that the influence of the individual genetic background on the risk of MS is modulated by the presence of some environmental factors, such as the number of years of direct exposure to younger siblings, early in life. In people with a specific genetic variant known to increase the risk of MS, having little or no exposure to younger siblings early in life, meant that they had a higher risk of developing MS than those who, despite having this “high-risk” genetic variant, had a lasting exposure to younger siblings early in life. Although these results need to be confirmed, they may help us understand better the pathogenesis of the disease, and give us hope that a high genetic risk of MS might be modulated (down-regulated) by increasing the contact with other infants early in life.
Source abstract

16 Mar 10

Clinico-pathological evidence that axonal loss underlies disability in progressive multiple sclerosis
Mult Scler. 2010 Mar 9

MS is a chronic inflammatory-demyelinating disease of the central nervous system, where some degree of irreversible disability can appear with time. Axonal degeneration, rather than demyelination, is believed to be the pathological substrate underlying such irreversible disability. However, so far there is little evidence to support this hypothesis. Through the post-mortem analysis of the cervical spinal cord of a group of people with MS, the authors of this study found a significant correlation between axonal loss in the major descending motor pathway and the degree of motor disability reached before death, supporting the hypothesis that neuro-axonal loss is the pathological substrate for progressive disability in MS.
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09 Mar 10

Ibudilast in relapsing-remitting multiple sclerosis. A neuroprotectant?
Neurology. 2010 Mar 3

Ibudilast is a new drug which, based on animal and pilot human studies, seems to have some anti-inflammatory properties, and reduce the damage to white matter in the brain, as observed in neurological diseases other than MS. The results of this multicenter, double-blind, phase 2 trial with oral ibudilast for people with relapsing-remitting MS, suggest that although no beneficial effect on the rate of newly active lesions and relapses was observed, ibudilast might act in a neuroprotective way and may have beneficial clinical effects on disability progression.
Source abstract

09 Mar 10

Antiviral immune response in patients with multiple sclerosis and healthy siblings
Mult Scler. 2010 Mar;16(3):355-8

The cause of MS is yet to be found. However, both environmental and genetic factors are believed to contribute to its pathogenesis. Amongst the environmental factors, viruses seem to play an important role. The authors of this article suggest that the nature of the immune response to Epstein-Barr virus is associated with the risk of developing MS.
Source abstract

09 Mar 10

Lesion enhancement diminishes with time in primary progressive multiple sclerosis
Mult Scler. 2010 Mar;16(3):317-24

MS is an inflammatory-demyelinating disease of the central nervous system. Although in primary progressive MS (PPMS), a form of MS characterised by clinical deterioration from the start, inflammation is considered to be less frequent than in other forms of MS, some acute inflammatory lesions in the brain and the spinal cord can be seen. In this longitudinal study carried out with people with PPMS, the authors found that a third of the participants experienced an early inflammatory phase, which seemed to have some impact on subsequent accrual of disability.
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09 Mar 10

Early cognitive impairment in multiple sclerosis predicts disability outcome several years later
Mult Scler. 2010 Mar 1

Clinical evolution in MS may vary widely amongst individuals, and the prediction of long-term clinical outcome is still far from satisfactory. It is well known that some people with MS may develop, with time, some degree of cognitive dysfunction. In this longitudinal study of people with MS, the authors found that a poorer cognitive performance, early in the disease, on tasks assessing verbal memory and information processing speed, was associated with a more rapid clinical worsening over the following years. The results of this study shed some light on the search for clinically relevant predictive markers of future disability, which can be very useful in adapting therapeutic strategies in the early stages of MS.
Source abstract

02 Mar 10

Anti-inflammatory effect by lentiviral-mediated overexpression of IL-10 or IL-1 receptor antagonist in rat glial cells and macrophages
Gene Ther. 2010 Feb 25

MS is a chronic inflammatory-demyelinating disease of the central nervous system (CNS). It is believed that the presence of an increased inflammatory activity in the CNS plays an important role in contributing to tissue damage. Using an animal model of MS, the authors demonstrated that it is possible to induce a decrease in the inflammatory processes of the CNS by introducing 'new' genetic information in cells involved in immune processes, through the use of specific viruses capable of transferring genes to other cells. They have also shown that by reducing the inflammatory activity, the clinical outcome improved significantly. The findings of this study may help design new therapeutic approaches.
Source abstract

02 Mar 10

Polymorphisms in the IL2, IL2RA and IL2RB genes in multiple sclerosis risk
Eur J Hum Genet. 2010 Feb 24

MS is a complex disease of unknown cause, where both environment and genes seem crucial for its development. The authors studied to what extent the presence of certain genetic variants, i.e. variants in three genes containing information of proteins specifically involved in immune reactions, had an influence on the risk of MS. They found significant correlations between such genetic variants and the MS risk, supporting the major role that genes related to immune processes play in the pathogenesis of MS.
Source abstract

02 Mar 10

Myelin activates FAK/Akt/NF-kappaB pathways and provokes CR3-dependent inflammatory response in murine system
PLoS One. 2010 Feb 23;5(2):e9380

In MS, an inflammatory-demyelinating disease of the central nervous system (CNS), degenerated myelin is believed to trigger deleterious inflammatory reactions in the brain. The authors demonstrated that in animal models of MS, degenerated myelin can also cause undesirable inflammation in the spinal cord, through the activation of a specific pathway. The findings of this study suggest that clearance of degenerated myelin or the blockage of such activated pathways might be considered, in future, as possible treatment strategies.
Source abstract

02 Mar 10

Inhibiting poly(ADP-ribose) polymerase: a potential therapy against oligodendrocyte death
Brain. 2010 Feb 15

Loss of oligodendrocytes (ODC), the cells providing the central nervous system with myelin, through a process of "programmed cell death" (i.e. apoptosis), is one of the most important pathological features of MS. However, the cause of this deleterious process is not yet known. The findings of this study suggest that the activation of a specific protein may be crucial for the appearance of apoptosis. Moreover, by inhibiting this very protein, the authors found that loss of both ODC and myelin decreased. The results of this study are encouraging, since inhibiting this crucial protein might represent a new and attractive therapeutic approach for MS.
Source abstract

23 Feb 10

Genome-wide association study in a high-risk isolate for multiple sclerosis reveals associated variants in STAT3 gene
Am J Hum Genet. 2010 Feb 12;86(2):285-291

MS is a complex disease of unknown cause where both genes and environment seem to have a role in its pathogenesis. The authors have investigated the impact that some specific genetic variants - recently linked to MS - have on the risk of MS, in an extensive group of people with MS and healthy controls in Finland. They found a specific genetic variant which had a protective role in MS. Interestingly this gene was found to have been previously associated to another autoimmune disease, suggesting a significant role of this gene in immune system and autoimmune disease pathogenesis.
Source abstract

23 Feb 10

Latitudinal variation in incidence and type of first central nervous system demyelinating events
Mult Scler. 2010 Feb 18

Although the cause of MS is unknown, environmental factors seem to play an important role in its development. In countries further away from the equator, the incidence of MS is believed to be higher than in countries that are closer to it. The findings of this study confirmed that the higher the degree of latitude, the higher the risk of the first inflammatory-demyelinating episodes suggestive of MS. Furthermore, the authors found that in areas further away from the equator, this increase in the incidence of first episodes suggestive of MS, was significantly higher in men than in women. Also, they found that the increase in the incidence of some types of first episodes, such as optic neuritis, was significantly higher than that for other types of episodes, such as spinal cord syndrome. This study will help us understand better the pathogenesis of MS.
Source abstract

23 Feb 10

Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta
Lancet Neurol. 2010 Feb 15

In this phase two, randomised, double-blind, placebo-controlled clinical trial, the authors aimed to investigate whether daclizumab reduced disease activity in people with active relapsing MS who were receiving interferon beta treatment. The findings of the study suggested that add-on daclizumab treatment reduced the number of active lesions compared with interferon beta alone and might reduce MS disease activity to a greater extent than interferon beta alone.
Source abstract

23 Feb 10

Early imaging predicts later cognitive impairment in primary progressive multiple sclerosis
Neurology. 2010 Feb 16;74(7):545-52

In MS, especially in progressive forms of the disease, some degree of cognitive dysfunction may appear with time. However, it is very difficult to predict who will develop such cognitive dysfunction. In this study on people diagnosed with primary progressive MS (PPMS), the authors found that certain MRI abnormalities, such as high lesion load and, to a lesser extent, damage in the grey matter, observed in scans performed in earlier stages of the disease, could predict future cognitive decline.
Source abstract

16 Feb 10

MRI of the corpus callosum in multiple sclerosis: association with disability
Mult Scler. 2010 Feb;16(2):166-77

The corpus callosum is one of the most important white matter tracts in the brain and forms the major connection between the two cerebral hemispheres, being involved in the performance of complex tasks. The corpus callosum is one of the regions of the brain affected in MS, but its study by conventional MRI techniques has not been satisfactory. The authors found that abnormalities in the corpus callosum can be assessed with new quantitative MRI techniques and are associated with cognitive and complex upper-extremity dysfunction in MS.
Source abstract

16 Feb 10

Atorvastatin Combined To Interferon to Verify the Efficacy (ACTIVE) in relapsing-remitting active multiple sclerosis patients: a longitudinal controlled trial of combination therapy
Mult Scler. 2010 Feb 11

Interferon beta (IFNb) is a first-line treatment for people with MS, but its efficacy may vary amongst different people. Statins are known to have anti-inflammatory properties. In this unicentre controlled clinical trial carried out with 45 participants, the authors aimed to assess safety, tolerability and efficacy of low-dose atorvastatin, which belongs to the group of statins, plus subcutaneous IFNb-1a (Rebif44®), given for 24 months, in people with MS responding poorly to interferon beta-1a. The people that received the combined therapy (atorvastatin plus IFNb-1a) had better outcome than those that received IFNb-1a alone, in terms of active inflammatory lesions in the MRI, relapses, and risk of increasing disability. The authors have concluded that low-dose atorvastatin may be beneficial, as add-on therapy, in poor responders to high-dose interferon beta-1a alone.
Source abstract

16 Feb 10

Clinical effect of neutralizing antibodies to interferon beta that persist long after cessation of therapy for multiple sclerosis
Arch Neurol. 2010 Feb 8

Interferon beta (IFNb) is a first-line treatment for people with MS. However, increasing evidence suggests that the presence of neutralising antibodies during treatment is associated with a reduction in treatment efficacy. The authors of this study found that anti-IFNb neutralising antibodies could persist after treatment cessation and were associated with higher disease activity and poorer clinical outcome.
Source abstract

16 Feb 10

The association between California Verbal Learning Test performance and fibre impairment in multiple sclerosis: evidence from diffusion tensor imaging
Mult Scler. 2010 Feb 11

It is known that memory disturbances can be a prevalent symptom in MS, having a detrimental effect on daily life. The authors aimed to investigate which memory processes were affected in MS, and their association with impairment of the brain white matter (WM) fibre tracts, by using the California Verbal Learning Test as a clinical tool. They found that people with MS mainly had impairments in encoding and consolidation, in contrast to other studies, claiming retrieval deficits as the main cause of memory disturbances in MS. Since they did not find significant associations between memory scores and impairment of WM fibre tracts, they suggest that further studies investigating compensatory brain mechanisms related to memory processes in MS are needed.
Source abstract

08 Feb 10

High field (9.4 Tesla) magnetic resonance imaging of cortical grey matter lesions in multiple sclerosis
Brain. 2010 Jan 31

Although MS has been traditionally considered as an inflammatory-demyelinating disease of the white matter (WM) of the brain and spinal cord, an increasing number of studies have demonstrated that the grey matter (GM) is also a major player in this disease. However, the MRI techniques currently used in clinical practice are not able to detect to what extent the GM is damaged in MS. In this article the authors show that very high field MRI techniques enable detection of not only cortical GM lesions, but also myelin content and neuronal density, in post-mortem MS brain, very accurately. This study represents a breakthrough in the study of the brain in MS by MRI techniques.
Source abstract

08 Feb 10

Learning from nature: pregnancy changes the expression of inflammation-related genes in patients with multiple sclerosis
PLoS One. 2010 Jan 29;5(1):e8962

It is well known that, during pregnancy, women with MS are likely to have a reduction in their disease activity. However, the biological mechanisms underlying these circumstances are poorly understood. The authors of this study found that specific changes in gene expression during pregnancy were associated with a decrease in disease activity. These findings may help us understand better the pathogenesis of MS.
Source abstract

08 Feb 10

Perivenous demyelination: association with clinically defined acute disseminated encephalomyelitis and comparison with pathologically confirmed multiple sclerosis
Brain. 2010 Feb 3

After a first inflammatory-demyelinating episode of the central nervous system, there are two main options for the clinical evolution that follows. Either the inflammatory-demyelinating process in the brain may continue (appearance of relapses and/ or progression of disability) with a diagnosis of multiple sclerosis, or the process can stop (with more episodes being unlikely) in a process called acute disseminated encephalomyelitis (ADEM). The differentiation between these two entities is crucial, since their management and prognosis are completely different. However, despite the different clinical features, the differentiation between them can be difficult. The authors of this study have found different patterns of demyelination for people with MS (confluent demyelination) and people with ADEM (perivenous demyelination). These findings contribute to the understanding of these two diseases and may help us differentiate them.
Source abstract

08 Feb 10

Inhibitory role for GABA in autoimmune inflammation
Proc Natl Acad Sci U S A. 2010 Feb 1

MS is an inflammatory-demyelinating disease of the central nervous system whose underlying pathogenic mechanisms are far from being completely understood. Through the study of animal models of MS, the authors suggest that GABA, the principal inhibitory neurotransmitter in the adult brain, may have an important influence on the inflammatory processes that occur in MS.
Source abstract

02 Feb 10

Allelic variation in the Tyk2 and EGF genes as potential genetic determinants of CNS repair
Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):792-7

Clinical evolution in people with MS may vary considerably amongst individuals. It is thought that this variability may be due, at least partly, to the fact that some people achieve good levels of tissue repair after a demyelinating insult. However, the mechanisms underlying this tissue repair are not well understood. The authors studied two strains of mice that differ significantly in their ability to repair damage in the central nervous system (CNS) after demyelination and they identified two regions in their DNA with a strong relationship to the ability to repair CNS tissue. Interestingly, these DNA regions contain genes related to proteins involved in cell growth and immune reactions. The findings of this study shed light on the complex processes underlying CNS repair in MS.
Source abstract

02 Feb 10

Brain tissue sodium concentration in multiple sclerosis: a sodium imaging study at 3 tesla
Brain. 2010 Jan 27

The authors aimed to investigate the underlying mechanisms of neuro-axonal degeneration, which is thought to play an important part in determining the increase in irreversible disability in people with MS, by means of a new MRI technique which specifically assesses the amounts of sodium in the brain tissue. They found abnormally high values of tissue sodium concentration in people with MS compared to healthy controls, and also that such tissue sodium concentration correlated with clinical disability, in keeping with other studies which suggest that the accumulation of sodium in axons is an important cause of axonal damage in MS.
Source abstract

02 Feb 10

Neurofilament light as a prognostic marker in multiple sclerosis
Mult Scler. 2010 Jan 19

The prognosis of MS may vary amongst people and as yet there are no significant markers which can predict a less favourable clinical evolution. The authors have found that, in people with relapsing-remitting MS (RRMS), higher levels of a protein called ‘neurofilament light’ (which supplies structural strength to neurons) in their cerebrospinal fluid were associated with a worse long-term prognosis. The authors suggest that elevated levels of neurofilament light could be used as a prognostic marker in early RRMS.
Source abstract

02 Feb 10

Spinal cord repair in MS. Does mitochondrial metabolism play a role?
Neurology. 2010 Jan 27

The authors aimed to investigate the mechanisms of spinal cord repair and their contribution to clinical recovery in people with MS after a cervical cord relapse. They used new MRI techniques which explore metabolite concentrations and tissue volumes in the spinal cord. They found that people who had a greater increase of a specific metabolite called NAA, which mainly reflects mitochondrial activity in the axon, had a greater clinical recovery. This suggests that mitochondrial metabolism plays a role in the mechanism of cord repair after a cord relapse in people with MS. They also found that this possible repair mechanism seemed less efficient in patients with longer disease duration.
Source abstract

26 Jan 10

A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis
Engl J Med. 2010 Jan 20

The authors of this article report the results of a 96-week clinical trial of a short-course oral tablet therapy with cladribine in people with relapsing-remitting MS. People who received cladribine tablets had a significantly lower rate of relapses, a higher relapse-free rate, and a lower risk of disability progression than the people who received the placebo. Furthermore, treatment with cladribine reduced MRI measures of disease activity. Since some adverse events related to cladribine treatment, such as decreased immune cell count and infection by herpes zoster, were observed, the benefits of this treatment need to be weighed against the risks.
Source abstract

26 Jan 10

A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis
N Engl J Med. 2010 Jan 20

In this 24-month, double-blind, randomised clinical trial, the efficacy of oral fingolimod relative to placebo in people with relapsing-remitting MS was investigated. As compared with placebo, oral fingolimod improved the relapse rate, the risk of disability progression, and MRI outcomes. However, further studies are needed to assess the safety and efficacy of oral fingolimod on the long term.
Source abstract