31 Jan 12

Immunogenic effects of recombinant interferon-beta therapy disrupt the JAK/STAT pathway in primary immune cells from patients with multiple sclerosis.
Mult Scler. 2012 Jan 27. [Epub ahead of print]

The authors aimed to assess the impact of Neutralising anti-bodies (Nabs) on Interferon-beta (IFN-β) responsive cells and signalling pathways in peripheral blood mononuclear cells. Peripheral blood samples from treated patients, untreated patients and healthy controls were used for analysis. The authors report that compared with controls JAK/STAT signalling pathways were modulated in treated NAb-negative patients and inhibited in all treated NAb-positive patients. Although these results are not readily transferable to the immunogenic response in patients they do demonstrate NAb effects on signalling within IFN- β responsive cells which may have wider implications in terms of immunogenic response in patients.
Source abstract

31 Jan 12

Measles IgG antibody index correlates with t2 lesion load on MRI in patients with early multiple sclerosis.
PLoS One. 2012;7(1):e28094. Epub 2012 Jan 19.

This new, interesting study aimed to correlate the antibody indices for the neurotropic viruses; measles virus, rubella virus, and varicella zoster virus with T2 lesion load in patients with clinically isolated syndrome and early relapsing remitting multiple sclerosis. The results show that intrathecal measles virus IgG production correlates with disease activity seen on spinal and brain MRI in patients with early disease. A similar correlation was seen with varicella zoster virus but this did not reach statistical significance. The authors comment that the reactions to these viruses form part of the polyspecific immune reaction in MS and may be of possible prognostic impact on MRI and clinical outcomes.
Source abstract

31 Jan 12

Brain viscoelasticity alteration in chronic-progressive multiple sclerosis.
PLoS One. 2012;7(1):e29888. Epub 2012 Jan 20

This interesting study from Germany utilises a new and emerging imaging technique called Magnetic Resonance Elastography (MRE) which is able to quantitatively measure biomechanical tissue properties in vivo. In this study the authors look at biomechanical tissue properties in patients with a chronic progressive course of MS and demonstrate that two viscoelastic parameters were reduced compared to healthy controls and also reduced compared to existing values found elsewhere in the literature for patients with relapsing MS.
Source abstract

24 Jan 12

Polysomnographic measures of disturbed sleep are associated with reduced quality of life in multiple sclerosis.
J Neurol Sci. 2012 Jan 16. [Epub ahead of print]

This interesting article from a Canadian research group evaluates the relationship between polysomnographic (PSG) parameters and health-related quality of life. The authors report analysis from 62 patients with MS, showing that PSG measures of sleep disruption were negatively associated (p<0.05) with Mental Component Summary (MCS) scores and that PSG parameters reflective of better sleep quality were positively associated with MCS scores.
Source abstract

24 Jan 12

FTY720 (Fingolimod) increases vascular tone and blood pressure in spontaneously hypertensive rats via inhibition of sphingosine kinase.
Br J Pharmacol. 2012 Jan 17. doi: 10.1111/j.1476-5381.2012.01865.x. [Epub ahead of print]

The authors report data from studies of the effect of the recently licensed MS drug FTY720 (Fingolimod) on vascular tone and blood pressure in hypertensive rats. They report that oral administration of FTY720 induced an increase in mean arterial pressure in hypertensive rats whereas a decrease in blood pressure was observed in normotensive rats. FTY720 induced major contractions in isolated carotid arteries from spontaneously hypertensive rats but not the normotensive rats. The authors suggest that FTY720 increases vascular tone and blood pressure in hypertensive rats, most likely due to its sphingosine kinase inhibitory effect.
Source abstract

24 Jan 12

Surgical therapy for multiple sclerosis tremor: a 12-year follow-up study
Eur J Neurol. 2012 Jan 17. doi: 10.1111/j.1468-1331.2011.03626.x. [Epub ahead of print]

This unique long term follow up study from the Mayo Clinic reports long term outcomes in a small cohort of patients with severe MS related tremor receiving deep brain stimulation or thalamotomy. Although the surgery was initially successful in all patients, the authors report a recurrence of tremor within a median of 3 months in all cases studied. The deep brain stimulation patients seemed to do best, with 2 patients tremor free at 5 years.

The authors concluded that the benefit from surgery for severe tremor in this cohort was short-lived (median 3months), with poor prognosis in the long term.
Source abstract

17 Jan 12

Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study.
Lancet Neurol. 2012 Jan 9. [Epub ahead of print]

This small but significant proof-of-concept study from the UK reports initial results following the intravenous administration of mesenchymal stem cells to ten people with secondary progressive MS. A dosing regimen based on body weight was used and no serious adverse events where reported following administration, though three people experienced mild, self limiting side effects.

The authors used paraclinical assessments of the visual pathway as clinical outcome measures and as a surrogate marker of wider disease. The results seem to suggest some structural, functional and physiological improvement after treatment in some visual endpoints which might be suggestive of neuroprotection.

Source abstract

17 Jan 12

Disruption of NMDA Receptors in Oligodendroglial Lineage Cells Does Not Alter Their Susceptibility to Experimental Autoimmune Encephalomyelitis or Their Normal Development.
J Neurosci. 2012 Jan 11;32(2):639-45.

This interesting study from the USA studied the effect of knocking out the gene encoding the oligodendroglial NR1 subunit which is essential for development of functioning NMDA receptors in EAE mice. They found that there was no significant difference between KO mice and non-KO mice in numbers of axons lost in spinal cord or severity of spinal cord demyelination. Nor did constitutive deletion of NR3A, a modulatory subunit of oligodendroglial NMDARs alter the course of MOG-peptide EAE. The results woud suggest that oligodendroglial lineage NMDARs are not significant participants in the pathophysiology of MOG-peptide EAE.
Source abstract

17 Jan 12

Multi-modal quantitative MRI investigation of brain tissue neurodegeneration in multiple sclerosis.
J Magn Reson Imaging. 2012 Jan 12. doi: 10.1002/jmri.23539. [Epub ahead of print]

This group from the USA used multimodal quantitative MRI to assess the relationship between lesions and neurodegenerative processes in people with MS. The case controlled study demonstrated that, not only is cerebral pathology widespread in RRMS as previously described, but analysis of quantitative MRI metrics from the corpus callosum and neocortex in relation to disability points to a neurodegenerative injury component that is independent from lesions.
Source abstract

10 Jan 12

Postmortem verification of MS cortical lesion detection with 3D DIR.
Neurology. 2012 Jan 4. [Epub ahead of print]

Data out from this well known MS research group from the Netherlands are now reported following their study to assess 3D double inversion recovery (DIR) MRI for detecting multiple sclerosis (MS) cortical lesions.

Using a direct postmortem MRI to histopathology comparison study design, they were able to demonstrate that the sensitivity for 3D DIR to detect MS cortical lesions was 18%, which is 1.6-fold higher than 3D fluid-attenuated inversion recovery (3D FLAIR). And that sensitivity improves to 37% with retrospective scoring; 2.0-fold higher than 3D FLAIR. The sequence was more sensitive at picking up mixed GM-white matter lesions with a sensitivity of 83% using (65% sensitivity for 3D FLAIR). For pure intracortical lesions 3D DIR was twice as effective as 3D FLAIR. The authors therefore conclude that the DIR sequence is more sensitive to detection of cortical lesions in MS than the 3D FLAIR sequence.
Source abstract

10 Jan 12

Evolution of MS lesions to black holes under DNA vaccine treatment.
J Neurol. 2012 Jan 6. [Epub ahead of print]

This interesting retrospective, blinded MRI study reports the analysis following a recent trial involving BHT-3009, a DNA plasmid-encoding myelin basic protein (MBP) that aims to reprogram the immune system to induce immunological tolerance to myelin antigens, in patients with MS. The authors were interested in assessing whether treatment reduces the risk of new lesions becoming persistent black holes (PBH), which are thought to be associated with disability progression in MS.

Although there was no impact of treatment on the risk for PBH overall, patients receiving a lower dose (0.5 mg) BHT-3009 showed a reduced risk of PBH in the presence of higher serum anti-MBP IgM antibody levels compared to placebo (p < 0.01). The authors therefore suggest that there may be an effect of low-dose BHT-3009, depending on the patients' pre-treatment immune responses.
Source abstract

10 Jan 12

Validation of the danish version of functional assessment of multiple sclerosis: a quality of life instrument.
Mult Scler Int. 2011;2011:121530. Epub 2011 Oct 30.

This new study from Danish researchers aims to validate the Danish language version of the functional assessment of multiple sclerosis (FAMS): a disease-specific instrument characterising the functional status of patients with multiple sclerosis.

Following a series of assessments as part of the validation process the authors concluded that the Danish version of FAMS appears to be an acceptable, valid, and reliable measure of current health and functional status of individuals with multiple sclerosis.
Source abstract

03 Jan 12

Magnetic resonance disease severity scale (MRDSS) for patients with multiple sclerosis: A longitudinal study
J Neurol Sci. 2011 Dec 28. [Epub ahead of print]

The authors from Boston, USA, report an improvement in the sensitivity for detecting longitudinal change of their previously described,'magnetic resonance disease severity scale (MRDSS), which combines measurements of T2-lesion volume (T2LV), T1-hypointense lesion volume (T1LV), and brain parenchymal fraction (BPF). A longitudinal study comparing the composite scale to its component parts showed that change in MRDSS was larger than the change in MRI subcomponents. MRDSS is reported to have particularly high sensitivity in relapsing-remitting MS.

Source abstract

03 Jan 12

Crucial Role of Granulocytic Myeloid-Derived Suppressor Cells in the Regulation of Central Nervous System Autoimmune Disease
J Immunol. 2011 Dec 30. [Epub ahead of print]

In this study by Greek researchers, the authors report that granulocytic myeloid-derived suppressor cells (G-MDSCs) abundantly accumulate within the peripheral lymphoid compartments and target organs of mice with experimental autoimmune encephalomyelitis prior to disease remission. Additionally, when G-MDSCs were transferred in vivo they produced an improvement in clinical outcome, delayed disease onset and significantly decreased demyelination. The results are interesting and the authors propose that these cells may be exploited for therapeutic purposes.
Source abstract

03 Jan 12

A nationwide survey of the prevalence of multiple sclerosis in immigrant populations of Sweden
Mult Scler. 2011 Dec 29. [Epub ahead of print]

The interesting epidemiological study from Sweden reports the results following analysis of MS prevalence amongst Sweden’s immigrant population. The authors calculated observed versus expected numbers of MS patients and gender- and age-specific prevalence ratios between immigrant populations and the general population of Sweden and, where possible, populations of the countries of birth.

In line with other similar studies, they found that MS prevalence increased in migrants who moved to Sweden from countries with a lower MS risk. Interestingly, in Iranian migrants the prevalence exceeded that in the general population of Sweden. The authors suggest this might indicate that Iranians carry genetic factors that contribute to a higher MS risk when environmental-lifestyle MS risk factors change.

Source abstract

20 Dec 11

Quantification of increased cellularity during inflammatory demyelination
Brain. 2011 Dec;134(Pt 12):3587-98.

Diffusion tensor imaging demonstrates an improved capability over standard magnetic resonance imaging to differentiate axon from myelin injury, but the increased cellularity and vasogenic oedema associated with inflammation cannot be separated from axon/myelin injury by diffusion tensor imaging, limiting its clinical applications. The authors have developed and assessed a novel diffusion imaging technique - diffusion basis spectrum imaging - to quantify baseline cellularity in the absence and presence of vasogenic oedema. An initial phantom study using fixed mouse trigeminal nerves juxtaposed with and without gel, followed by in vivo animal study in cuprizone treated mice, demonstrated that in vivo diffusion basis spectrum imaging can effectively separate the confounding effects of increased cellularity, allowing successful detection of immunohistochemically confirmed axonal injury and/or demyelination. The results suggest that diffusion basis spectrum imaging has potential as a future non-invasive biomarker for neuroinflammation.
Source abstract

20 Dec 11

Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla
Brain. 2011 Dec;134(Pt 12):3599-612.

This study combined a mixture of imaging and histological techniques to assess whether cerebral iron deposition in MS was detectable using imaging measures and found that in MS tissue, iron presence invariably matched with an increase in transverse relaxivity, R(2)*. The authors found a number of cellular iron sources, including oligodendrocytes in normal-appearing white matter, and activated macrophages/microglia at the edges of white matter lesions. However although the imaging techniques were quite sensitive at detecting changes in areas of iron accumulation, these changes do not necessarily always reflect pathology and may also be seen in apparently normal tissue.
Source abstract

20 Dec 11

Diffusion tensor imaging of normal-appearing white matter in neuromyelitis optica
J Neuroradiol. 2011 Dec 13. [Epub ahead of print]

In this study, diffusion tensor imaging is used to assess fibre coherence within normal appearing white matter (NAWM) in the brain and spinal cords of patients with NMO. The authors report a decrease in functional anisotropy (FA), the degree to which diffusion is restricted (used as a measure of fibre integrity) in the posterior limb of the internal capsule, in the optic radiations and in spinal cord NAWM. FA was also significantly lower in spinal cord lesions. Overall the results suggest the presence of severe DTI abnormalities within the spinal cord lesions of patients with NMO, and within NAWM in the optic radiation and corticospinal tracts, although it remained normal in NAWM outside these tracts.
Source abstract

13 Dec 11

The Multiple Sclerosis Work Difficulties Questionnaire
Mult Scler. 2011 Dec 6. [Epub ahead of print]

This useful study from Australia validates the new Multiple Sclerosis Work Difficulties Questionnaire (MSWDQ) consisting of 50 items developed and reviewed by a panel of experts measuring 12 factors.

Following community testing of 189 people with MS, the authors conclude that the MSWDQ is a valid and internally reliable measure of workplace difficulties in patients with MS, and that difficulties identified could be used to predict workplace outcomes and expectations about future employment.
Source abstract

13 Dec 11

Comparison of two dosing frequencies of subcutaneous interferon beta-1a in patients with a first clinical demyelinating event suggestive of multiple sclerosis (REFLEX): a phase 3 randomised controlled trial
Lancet Neurol. 2011 Dec 2. [Epub ahead of print]

This randomised controlled treatment trial assessed two regimes of Rebif Vs Placebo for up to 24 months in a large cohort of 517 patients with clinically isolated syndrome.

The results from the study show a significant reduction in numbers converting to MS (as defined by the 2005 McDonald criteria) and clinically definite MS (as defined by the Poser criteria) during the follow-up period in patients receiving Rebif either once a week or three times a week, compared to placebo. The authors comment that potential differences seen between the regimens warrant longer-term study.

Source abstract

13 Dec 11

Inflammatory Cortical Demyelination in Early Multiple Sclerosis
N Engl J Med 2011; 365:2188-2197December 8, 2011

This study from the Mayo Clinic, Rochester, characterises the prevalence and character of demyelinating cortical lesions in patients with early MS.

Patients undergoing stereotactic brain biopsy with sufficient grey matter in the sample were included in the analysis. Cortical demyelination was present in 38% of patients. In many of the lesions CD3+ T-cell infiltrates and, to a lesser exten,t macrophage-associated demyelination, were observed. In patients who had sufficient meningeal tissue for study, meningeal inflammation was also found to be topographically associated with cortical demyelination.

Source abstract

06 Dec 11

Prevalence of MS: Door-to-Door Survey in Three Rural Areas of Coastal Black Sea Regions of Turkey
Neuroepidemiology. 2011 Dec 1;37(3-4):231-235. [Epub ahead of print]

This paper provides unique epidemiological data on the prevalence of multiple sclerosis in Turkey. The study was undertaken in three rural areas of Turkey at the same latitude, near 40° north latitude on the Black Sea coast using a door-to-door survey. Taken together, the regions studied showed a prevalence of 51/100,000. This prevalence was roughly half the 101/100,000 prevalence found in Istanbul in a recent similar study by the same group.
Source abstract

06 Dec 11

Mobility, balance and falls in persons with MS
PLoS One. 2011;6(11):e28021. Epub 2011 Nov 22.

This study examined the relationship between commonly used disease scores and walking assessments, and the risk of falls in patients with MS.

Results suggest that patients with MS who are older, more disabled, use an assistive device, have decreased walking coordination and endurance, and have diminished balance are at higher risk of falls; the authors suggest that they need to be monitored more carefully

Source abstract

06 Dec 11

Feasibility and outcome of a web-based self-help intervention for depressive symptoms in patients with multiple sclerosis: A pilot study
J Neurol Sci. 2011 Nov 29. [Epub ahead of print]

The authors report on the results of this initial pilot study, examining the feasibility and outcome of an applied web-based problem solving therapy intervention to reduce depressive symptoms in MS patients. The results suggest that it reduces depressive symptoms, however, the authors comment that ways to improve compliance should be considered and that a larger randomised controlled trial is needed.
Source abstract

30 Nov 11

Therapeutic Dosing of Fingolimod (FTY720) Prevents Cell Infiltration, Rapidly Suppresses Ocular Inflammation, and Maintains the Blood-Ocular Barrier
Am J Pathol. 2011 Nov 23. [Epub ahead of print]

This interesting study from the UK examines the effects of the MS drug fingolimod on experimental autoimmune uveoretinitis in mice, a preclinical model of human uveitis - inflammation of the middle layer of the eye - which allows assessment of immunotherapeutic efficacy. Results from the experiment show that high-dose fingolimod treatment administered before disease onset reduces ocular infiltration within hours of administration and suppress the development of pathology, whilst in established disease a treatment regime using a dose similar to that in current MS patient protocols significantly reduced infiltration within 24 hours of administration and maintained the blood ocular barrier. On withdrawal of fingolimod, drug-induced remission was lost.
Source abstract

30 Nov 11

An automated tool for detection of FLAIR-hyperintense white-matter lesions in Multiple Sclerosis
Neuroimage. 2011 Nov 18. [Epub ahead of print]

This group from Germany have developed and evaluated an automated lesion detection algorithm requiring a three-dimensional (3D) gradient echo (GRE) T1-weighted and a FLAIR image at 3 Tesla (T).

The group evaluated the algorithm in 53 MS patients with different lesion volumes, including a group with posterior fossa lesions and 18 control subjects. They found good agreement with lesions determined by manual tracing. Initial results are promising but require further validation with data from other protocols based on a conventional FLAIR sequence and a 3D GRE T1-weighted sequence.


Source abstract

30 Nov 11

Sensory evoked potentials to predict short-term progression of disability in multiple sclerosis
Neurol Sci. 2011 Nov 27. [Epub ahead of print]

The authors from Italy aimed to devise a multivariate parametric model for short-term prediction of disability using the Expanded Disability Status Scale (EDSS) and multimodal sensory evoked potentials (mEP). By performing a retrospective analysis of 221 MS patients who underwent repeated mEP and EDSS assessments at variable time intervals over a 20-year period, they were able to show that a parametrical regression model combining EDSS and mEPS accurately predicts short-term disability in MS patients, and suggest that it could be used to optimise decisions concerning treatment.

Source abstract

22 Nov 11

Evaluation of safety monitoring guidelines based on MRI lesion activity in multiple sclerosis
Neurology. 2011 Nov 16. [Epub ahead of print]

This interesting paper from Canada examined the sensitivity of a standardised protocol for monitoring safety in MS clinical trials. By looking for five or more contrast enhancing lesions above the baseline count on follow up MRI after study recruitment, the authors assessed the sensitivity of such a monitoring process for predicting relapse and found that RRMS patients meeting the radiological threshold had a statistically significant increase in odds ratio of relapse. However no significant findings were noted in the SPMS patients after applying the protocol. The authors conclude that a guideline based on crossing a threshold CEL count above baseline may be valuable in monitoring patient safety.
Source abstract

22 Nov 11

Independent replication of STAT3 association with multiple sclerosis risk in a large German case-control sample
Neurogenetics. 2011 Nov 18. [Epub ahead of print]

This group from Germany performed a genetic association study of two Signal transducer and activator of transcription 3 (STAT3) gene polymorphisms (rs744166 and rs2293152) in a large, independent German case-control sample of 5,904 subjects. They found a nominally significant, albeit weak association between rs744166 and MS susceptibility (odds ratio=1.09, P=0.012) in their sample which seems to support other recent genome wide association studies implicating STAT3 in MS susceptibility. Since STAT3 plays an important role in regulating the differentiation and proliferation of Th17 lymphocytes, the authors suggest that their results support the involvement of Th17 lymphocytes in MS.
Source abstract

22 Nov 11

Conformational epitopes of myelin oligodendrocyte glycoprotein are targets of potentially pathogenic antibody responses in multiple sclerosis
J Neuroinflammation. 2011 Nov 17;8(1):161. [Epub ahead of print]

In this interesting study examining the sera of of 325 MS patients, 69 patients with clinically isolated syndrome and 164 healthy controls for reactivity to 3 different isoforms of myelin oligodendrocyte glycoprotein (MOG), a putative autoantigen in MS, the authors report that in patients with relapsing-remitting MS high-titres of anti-MOG IgG correlated with disability (evaluated by EDSS) but that the vast majority of samples contained only low titres of anti-MOG.

The authors found that MOG reactivity is non-ubiquitous, as seen in other studies, and conclude that in patients with high-titres are likely to represent a higher affinity of antibodies against pathologically relevant MOG epitopes, that are only present in a small proportion of patients with MS.
Source abstract