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American Academy of Neurology Annual Meeting: Toronto, Canada, 10-17 April 2010.

The issue stimulating the most discussion and controversy was the proposal of Dr Zamboni from Italy that multiple sclerosis (MS) may be caused by impaired venous drainage from the brain and spinal cord due to partial obstruction to venous flow in the neck and chest--so-called chronic cerebrospinal venous insufficiency (CCSVI). Dr Zamboni gave an invited lecture and the AAN took the unusual step of co-hosting (with the US National MS Society) a live forum on the worldwide web where Dr Zamboni discussed the issues with three other experts in the field. The forum included over 4000 registrants on the website. A poster by Dr Zivadinov from Buffalo, New York, USA did not confirm the remarkable results of Dr Zamboni, where 100% of those with MS were reported to have venous abnormalities, not seen in any persons with other neurological diseases (OND) or healthy individuals. In Buffalo, venous abnormalities were found in 56% of MS patients (38% in those with a first MS attack), 42% of individuals with OND and 22% of healthy people, indicating the abnormality is not specific for MS and of uncertain relevance. It was widely considered inappropriate to refer those with MS for potentially hazardous venous corrective procedures on the current evidence.

Reports on developing treatments included updates on trials of promising oral immunomodulators, particularly fingolimod, cladribine and teriflunomide (the latter in combination with glatiramer acetate [GA]), and confirmation of prolonged effects of the monoclonal antibody alemtuzumab. A disappointing result was the negative trial of the oral a4 integrin inhibitor CDP323--the reasons for the lack of effect are not clear, given the established effect of the monoclonal antibody natalizumab, which inhibits the same receptor. There was also no evidence that omega-3 fatty acids reduce inflammatory activity in a 6-month trial.

With respect to established first-line disease-modifying treatments, two reports confirmed the long-term safety of interferon beta, and a pilot study suggested GA may be as effective when given twice weekly rather than daily. Several studies addressed the effectiveness of treatment with natalizumab and the risk of progressive multifocal leucoencephalopathy (PML) which increases at least up to 3 years of treatment and is of the order of one in 1000. A new assay for serum antibodies to JC virus (indicating past exposure) may prove to be a guide to PML risk.

The possible place of vitamin D as immunomodulatory treatment of MS remains unestablished although large doses are taken by many patients with MS. There were also reports implicating relative vitamin D deficiency in early life as a possible predisposing factor in MS risk. There was support for a beneficial effect of statins in reducing central nervous system inflammation.

With respect to symptomatic treatment, a review of three trials of dalfampridine indicated the reported improvement in walking speed was sufficient to be clinically meaningful. Two reports noted that dextromethorphan plus quinidine, previously shown to be helpful for pseudobulbar affect, was safe and tolerable. However, donepezil showed no benefit for mild cognitive impairment in MS.

Several studies addressed aspects of MS in children, particularly the distinction from other related inflammatory disorders. Several studies addressed the uncertain relationship between auto-immune responses to aquaporin-4 and neuromyelitis optica.

A new website (msgene.org) was presented which provides a systematic summary of over 800 MS genetic association studies, and should help substantially in the interpretation of a complex field. In general, reports of studies of aspects of genetics and immunology in MS did not provide any substantial new insights

The John Dystel prize for MS research was awarded to Professor David Hafler of Yale University for his work in immunology and genetics of MS.

Disclosures

The author has received support from Bayer Schering Pharma, Biogen Idec, Sanofi-aventis and CSL to attend meetings, and is engaged in clinical trials in MS with Biogen Idec, GlaxoSmithKline and Sanofi-aventis.

Ernest Willoughby

Auckland, New Zealand
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Author:Willoughby, Ernest
Publication:The International MS Journal
Article Type:Conference notes
Geographic Code:1USA
Date:Jul 1, 2010
Words:638
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