Neurologists speak-out about CCSVI!
Click here for: Khan et al. Ann Neurol. 2010 Mar;67(3):286-90.
Progressive loss of nerve fibres in the eye in MS
Using a very cool technology called optical coherence tomography (OCT) a new study has demonstrated progressive thinning of the retinal nerve fibre layer as a function of time in some patients with MS. Importantly, this thinning occurred in either the presence or absence of previous optic neuritis (focal inflammation in the optic nerve) and was associated with clinically significant visual loss.
These findings indicate that asymptomatic or sub-clinical nerve fibre (or axonal loss) occurs in the visual pathways in MS.
Opinion:
1. If these findings can be confirmed it will add credence to the claims that MS is a primary neurodegenerative disease. “I hope not.”
2. This study supports the use of OCT as a method to evaluate the effectiveness of neuroprotective agents in MS; we will need to show that drugs or combinations of drugs stop or at least slow down this loss of nerve fibres to accept that they are “neuroprotective”.
Early life factors in MS
We need your help with a survey investigating early life factors in MS. If you have MS and are willing to help please complete the following survey:
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Top up Vitamin D in the sun or pop a supplement, say researchers
Sativex in MS-related spasticity
Treating spasticity in MS is a big problem; it is very common and the current drugs we use are too sedating and tend to have a negative impact on cognition, which limits their use early on in the course of the disease.
This study compares Sativex (the active ingredient in cannabis) with placebo in a 15-week study. The design of this study is interesting for two reasons: (1) it used an enrichment phase to select responders before randomising them to blinded active comparator stage of the trial; and (2) it used a numeric rating scale (NRS) as the primary outcome rather than the Ashworth scale (the traditional outcome measure in spasticity trials). In summary the change in NRS score and responder-status (defined as a greater than or equal to 30% improvement from baseline) were both significantly superior for Sativex, compared with placebo. Importantly, Sativex appears to be well tolerated in this group of patients with quite advanced MS.
It will be interesting to see if Sativex gets a license based on the results of this trial. The availability of Sativex will allow us to “spread the hope” and offer something to patients in whom our current medications are not enough to control their spasticity.
Vitamin D status is associated with relapse rate in pediatric-onset MS
Among 110 North American paediatric CIS/MS subjects, every 10 ng/mL increase in the adjusted 25 hydroxyvitamin D3 level was associated with a 34% decrease in the rate of subsequent relapses.
This study adds compelling evidence in support of a role for vitamin D in reducing MS relapse rates as initially seen in smaller studies in adult MS cohorts (Wingerchuk et al, JNNP 2005; Soilu-Hänninen et al, JNNP, 2008). As vitamin D deficiency/insufficiency is endemic worldwide (Holick, NEJM, 2007), further studies of vitamin D as a treatment measure in MS are warranted.
Sreeram Ramagopalan
43 confirmed post-marketing Natalizumab-related cases of PML
The news of 43 confirmed cases of post-marketing Natalizumab-related PML coincides with the timely publication of the description of the first 28 such cases and a review on the topic:
These developments underpin the urgent efforts to implement an appropriate risk-stratification strategy to lower the risks of developing PML for people with MS receiving Natalizumab.
Please watch this space for an update.
Human leukocyte antigen-DR15, low infant sibling exposure and multiple sclerosis: Gene-environment interaction
The cause of multiple sclerosis (MS) is not yet conclusively known but both genes and the environment are important. A region on chromosome 6, the HLA class II, exerts the single strongest genetic effect but the involvement of the environment is also inescapable and is no better illustrated than by the geographical distribution of the disease. The identity of the environmental factors involved in MS is not known unequivocally but there are a few leading candidates, namely, Epstein-Barr virus, vitamin D and smoking. It has been suggested that low sibling infant exposure (classed as having no older siblings and any younger siblings having an age difference of at least 5 years) increases MS risk (Ponsonby et al, JAMA, 2005). Genetic and environmental factors are not independent. In an intriguing study, van der Mei and colleagues observed that HLA-DRB1*15 (a form of the gene involved in MS on chromosome 6) interacted with low sibling infant exposure to increase MS risk. This result could thus be of importance in disease aetiology but requires replication. Other groups have been unable to support an effect of low infant sibling exposure on the risk of MS (Sadovnick et al, Lancet Neurol, 2005; Bager et al, Am J Epidemiol, 2006) so the gene-environment interaction uncovered by van der Mei and others may be specific to Australia; this will require confirmation.
Dr Sreeram Ramagopalan
2010 Annual Evidence Update on Multiple Sclerosis
You may find the following NHS resource useful:
Absence of Epstein-Barr virus in the brain and CSF of patients with multiple sclerosis
Another blank. Sargsyan and colleagues failed to find evidence of persistent infection in the cells that produce antibodies (plasma and B cells) within the brains of people with MS. Only in active MS plaques was EBV-encoded RNA (EBER)-1 rarely detected.
Conclusion: My take on this is that we need to focus on active and preactive MS lesions; I suspect that is where the action will be. Although the score at the moment is strongly against overt CNS EBV infection being a direct factor in MS pathogenesis we need to keep an open mind to the contrary. Post-mortem tissue studies are not necessarily the best means of investigating the link between active EBV infection within the central nervous system and MS.