Saturday, 21 July 2018

The influence of spinal cord volume loss

Although it is not always done, spinal cord imaging may help to see what is in store for your leg function.

Friday, 20 July 2018

How can we create a prevention study in MS? We need your help!

Many of you will have seen the previous post on Preventive Neurology and the new initiative we are setting up to work towards preventing MS. As many of the comments have identified, this is a difficult area to study. We have to find a way to start monitoring people before they develop the earliest signs of MS. 

                  

Thursday, 19 July 2018

We need feedback on our new listeriosis prevention pack - can you help?

We've now developed our listeriosis prevention pack and would like 10 people to test it out and give us feedback to improve it further. 













     


Wednesday, 18 July 2018

Stornoway research day series: Diagnosing and treating relapses

Dr Sarah Martin talks about how to define and treat a relapse in multiple sclerosis, for healthcare professionals working on the Western Isles.




Tuesday, 17 July 2018

Stornoway research day series: Biomarkers in MS

Doc Neuro Gnanapavan discusses biomarkers in multiple sclerosis, to an audience of healthcare workers on the Western Isles. She defines what biomarkers are, and why they are useful for diagnosing and monitoring MS. 





Monday, 16 July 2018

We need your thoughts

The MS Society in the UK is committed to finding treatments for progressive MS, and have ambitious plans to make that happen as quickly as possible.

They have been asking the question
Which existing drugs could help in progressive MS?

Can you help?

Remyelination. Is ivermectin the next great thing or something dangerous?

What do Remyelination, Parasites and Collie Dogs have in common?

Sunday, 15 July 2018

How do CD20-depleting antibodies work..To T or Not to T that is the Question.

As soon as rituximab and then ocrelizumab, which are both CD20 depleting antibodies, were shown to influence relapsing MS, implicating B cells as a target for MS.

We had a flow of papers indicating that T cells express weak amounts of CD20. This view is trotted out time and time again, if you mention B cells as an issue.

These T cells are depleted by rituximab and so the T cell biologists have clung to the idea that rituximab works by depleting T cells.

Palanichamy A, Jahn S, Nickles D, Derstine M, Abounasr A, Hauser SL, Baranzini SE, Leppert D, von Büdingen HC. Rituximab efficiently depletes increased CD20-expressing T cells in multiple sclerosis patients. J Immunol. 2014;193:580-586.

Is this a desperate view to cling to? 

I think so

(A) The Tcellers are happy to accept that depleting 5% of T cells (i.e. the CD20+ T cell subsets) inhibits MS, whilst dismissing the fact that 70% depletion of (CD4) has minimal effect. This makes minimal sense to me

(B) However, it is not only CD20 that implicates activity on B cells. 

Do T cells express Bruton Tyrosine Kinase and CD19, because these B cell depleting agents also work in relapsing MS.

The answer is here.

Schuh E, Berer K, Mulazzani M, Feil K, Meinl I, Lahm H, Krane M, Lange R, Pfannes K, Subklewe M, Gürkov R, Bradl M, Hohlfeld R, Kümpfel T, Meinl E, Krumbholz M. Features of Human CD3+CD20+ T Cells. J Immunol. 2016;197:1111-7. 


"These cells display a lower level of CD20 than B cells and lack markers typically found on B cells such as HLA-DR, CD40 and CD19".

"We sorted CD3+CD20+ cells, CD3+CD20 T cells, and CD19+CD20+ B cells from healthy donors to compare their transcript levels of CD3, CD19, and CD20 by quantitative PCR"......they got


Yep the same result, the CD20+ T cells are not going to be hit by CD19-depleting antibodies.

So can the effect of CD19 depleting antibodies be explained via a T cell mechanism?

Maybe its time to think that really CD20 works, because its depleting B cells.

Saturday, 14 July 2018

Stornoway research day series: Using technology to support an MS service

Iain Trayner runs a technology enabled care (TEC) programme on the Western Isles. They research, source funding and roll out digital technology that supports patient care.




Friday, 13 July 2018

Stornoway research day series: Symptomatic problems

Dr Pushkar Shah discusses symptomatic treatments for MS, as opposed to disease modifying treatments. What treatments are out there to alleviate MS symptoms?





Thursday, 12 July 2018

Hunting for Treatments for Progressive MS.

There are a number of initiatives from the multiple sclerosis societies aiming to hunt and test for treatments for progressive MS.

People are screening public data bases to see if they can get ideas for candidates to test.

We will soon have the results of one of these approaches with the delivery of results from the United Kingdom MS-SMART study. This has tested the influence of fluoxitine (sertonin-reuptake inhibitor), riluzole (a glutamate receptor and ion channel blocker) and amiloride (an acid sensing ion channel blocker) in secondary progressive MS.

Fluoxetine was next on the list after Ibudilast but that was tested in the MS-SPRINT trial undertaken in the United States, which has also finished.

However, the MS Societies have not finished and they want to test more. 

So they need: 

(a) An optimum trial design to test the agents and 
(b) the agents.

The pharma approach is to innovate or to innovate to re-engineer existing targets to get a patent and then test.

The academic approach is to repurpose existing generic drugs.

Academia has found candidates should we give them a go?

Wednesday, 11 July 2018

Ask a Question July

If you have a question unrelated to other posts.

This is the place for you
 Pic by MD2 Derwent Water

MRI: A land of confusion?


When patients present with typical clinical and radiological features, MS is not difficult to recognize. However, things are not always what they seem to be at first glance!


Tuesday, 10 July 2018

Early changes in MS

PLoS One. 2018 Jul 6;13(7):e0200254. doi: 10.1371/journal.pone.0200254. eCollection 2018.

Health-related quality of life, neuropsychiatric symptoms and structural brain changes in clinically isolated syndrome.


Monday, 9 July 2018

Guest Post: MS ‘North of The Wall’

Scotland – the land of bagpipes, haggis, lochs and… multiple sclerosis.



By © User:Colin / Wikimedia Commons, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=42803168


Sunday, 8 July 2018

Saturday, 7 July 2018

Disease activation after abortion

We know that pregnancy reduces the risk of attacks.

Likewise we know that you are risk of attacks, after the baby has been born.

So what happens after an adorption?

Nerve transmitter receptor inhibits myelinating cell formation-Block it to get remyelination

The neurotransmitter acetyl choline binds to muscarinic receptors.


Clemastine  is a muscarinic receptor blocker and stimulates remyelination

Benztropine is remyelinating agent that is a muscarinic receptor blocker too. However, these are dirty drugs and bind to many things, meaning the potential for unwanted side effects.

There are five types of Muscarinic receptors M1-M5 

Which ones are the important ones?....Interested? Read On

Friday, 6 July 2018

Preventive Neurology

Avid readers of this blog will have probably noticed that Prof G has been increasingly focusing on new initiatives recently. One of these is Preventive Neurology - as part of this we have received a large grant to set up a Preventive Neurology Unit, based at the Wolfson Institute of Preventive Medicine within QMUL. 



But what does preventive neurology have to do with MS, given that we can’t even be sure as to the cause of MS? And how will this work? 

Thursday, 5 July 2018

NHS@70: postcode prescribing and doing something about it

Today is the NHS' 70th Birthday. Happy Birthday we love you! 



We know you are the best value for money health service in the world and that you try your best with limited resources. We want to pledge our support for you and help you make the next 70 years even better. 


Wednesday, 4 July 2018

MS Brain Health newsletter – June 2018



Dear supporters 
Over the past month, we have presented MS Brain Health research at major conferences in Europe, the USA and Australia and learned more about the experiences of people living with MS in the USA. It has been great to meet some of you in person at these events, and we are pleased to welcome many new supporters!
Consensus standards presented at EAN 2018 
International consensus standards for the timing of key stages in MS care were presented in our focused workshop, Brain Health in MS: a catalyst for a new approach to management, at EAN 2018 in Lisbon this month. Over 150 attendees joined this interactive workshop and gave their responses to the new quality standards.
Professor Gavin Giovannoni, Dr Gisela Kobelt and Professor Jeremy Hobart gave presentations and participated in a lively Q&A session. "The standards should not be used as a means to criticize MS teams, but instead provide an opportunity for every MS clinic to strive for the highest level of care," stressed Professor Hobart.
Read more
Latest MS Brain Health presentations available to download
Professional organizations in Australasia endorse the policy report
MS Nurses Australasia and the MS Neurology subspecialty group of the Australian and New Zealand Association of Neurologists have become the latest professional groups to officially endorse the policy report, Brain health: time matters in multiple sclerosis. We're delighted that these groups have joined our other 46 endorsers.
Revisions to criteria used in the diagnosis of MS
Motivated by recent technological advances and new data on the diagnosis of MS, experts have refined the 2010 McDonald criteria – the widely used diagnostic criteria for MS. The experts hope that the updated criteria will facilitate early and accurate diagnosis of MS.
Read more
New! Dutch translations of short guides
We are delighted to announce that our guide for people with MS and nursing resource are now available in Dutch. Follow the links above, click 'Download' and select your language.

Please do share these resources with your Dutch-speaking colleagues and friends.
You can follow us on Twitter @MSBrainHealth to keep up with the latest news. Thank you for your continuing support!
Gavin Giovannoni, MD

Professor of Neurology and Chair of the MS Brain Health Steering Committee

On behalf of the MS Brain Health Steering Committee: Gavin Giovannoni, Peer Baneke, Helmut Butzkueven, Jodi Haartsen, Jeremy Hobart, Gisela Kobelt, Christoph Thalheim, Tony Traboulsee, Tim Vollmer and Tjalf Ziemssen
 
If this newsletter has been forwarded to you,
click here to subscribe to future issues.

Follow @MSBrainHealth on Twitter
Having trouble viewing the content of this post? View this post in your browser
MS Brain Health activities and supporting materials are funded by grants from Actelion, Celgene and Sanofi Genzyme and by educational grants from Biogen, F. Hoffmann-La Roche and Merck KGaA, all of whom have no influence on the content.

Editorial and administrative support for the MS Brain Health initiative is provided by Oxford Health Policy Forum, a not-for-profit community interest company registered in England and Wales (registration number: 10475240).

Tuesday, 3 July 2018

Antibodies to PEG interferon may affect its action

Int Immunopharmacol. 2018 Jun 27;62:1-6. doi: 10.1016/j.intimp.2018.06.030. [Epub ahead of print]

Interaction of PEGylated interferon-beta with antibodies to recombinant interferon-beta.

Gilli F, De La Torre AL, Royce DB, Pachner AR.

Abstract


Because PEGylated molecules exhibit different physicochemical properties from those of the parent molecules, PEGylated interferonβ-1a (pegIFNβ-1a) may be able to be used with retained bioactivity in Multiple Sclerosis (MS) patients who have previously developed neutralizing antibodies (NABs) to recombinant interferonβ (rIFNβ). Hence, the objective of the present study was to test whether pegIFNβ-1a is less antigenic for NABs in vitro than rIFNβ. Two in vitro assays were used to quantitate NABs in 115 sera obtained from MS patients included in the INSIGHT study: the cytopathic effect (CPE) assay, and the MxA protein induction assay. NABs cross-reactivity was assessed by comparing dilutions of serum with fixed doses of rIFNβ-1a Avonex® and pegIFNβ-1a Plegridy®. NABs were shown to cross-react in both assays. The y-intercept (c), the slope of the line of agreement (b), the Pearson coefficients as well as the Bland-Altman analysis, indicated that there is good level of agreement between NAB titers against the two IFNβ-1a formulations, with both the CPE (c = 0.1044 ± 0.1305; b = 0.8438 ± 0.06654; r2 = 0.587; bias index ± SD = -0.01702 ± 0.6334), and the MxA protein induction (c = 0.08246 ± 0.1229; b = 0.8878 ± 0.06613; r2 = 0.615; bias index ± SD = -0.09965 ± 0.6467) assays. Until further in vivo evidence is established, clinicians should consider the current in vitro data demonstrating NAB cross-reactivity between pegIFNβ-1a and rIFNβ when discussing new treatment options with MS patients.



Monday, 2 July 2018

EBV in the brain

Epstein Barr Virus (EBV) is a herpes virus which is spread by saliva and infects around 95% of us during our lifetimes. In the majority of people EBV infection does not cause prominent symptoms - it may cause a ‘flu-like’ illness which gets better on its own, or it may go completely unnoticed.

Sunday, 1 July 2018

Stornoway research day series: Diagnosing MS

Prof G outlines how a neurologist will go about diagnosing MS. He explains the difficulties in diagnosing it before symptoms appear, and the difficulties neurologists have dealing with "Dr Google". 




Saturday, 30 June 2018

Stornoway research day series: How do disease modifying therapies work?



The Mouse Doc explains how disease modifying therapies work in the body to help to treat multiple sclerosis. He describes the problems with the animal model of MS, and the fact that the disease may well be a B-cell disease, rather than a T-cell disease.





Friday, 29 June 2018

Guest post: MS Perceptions: help us understand how we understand MS

It is actually surprising how little most people know about MS. 

This is important because people who know someone with MS usually want to offer help and support, but don’t know what to offer. 

Thursday, 28 June 2018

Off-label disease modification for people with multiple sclerosis in resource poor settings.

Drugs are rationed on the basic of cost-effectiveness. This is all well and dandy if you live in a place where you can get access to treatment x or y because you have socialized medicine or access to a health insurance scheme. 

However, live outside these regions and your annual income may be less than the cost of all current MS drugs.

If you live as a pwMS or work as a Neurologist in a resource poor country you need to read this paper. This was written by one of our Non-UK based Neurologists. It is open access and can be read by anyone.

Wednesday, 27 June 2018

Stem cell therapies for MS - why we need to get it right

Hi, my name is Niall (pronounced Neil) and I'm a neurologist working with people affected by MS in the West of Scotland area.

I grew up in Lanarkshire and I became interested in MS when I was working as a trainee in Dundee.  It's a complex disease and looking after people affected by MS in clinic gives you a chance to get to know them a bit over the years which is quite nice.  It's also fairly sad when you see how much damage uncontrolled MS can do to a person.



Monday, 25 June 2018

MS in the courtroom

We have made the case in the past that one of the ways healthcare professionals will begin to treat MS more actively is via the courts. In the meeting below we will be presenting a hypothetical case scenario of a patient who lost brain due to a delay in diagnosis and a delay in accessing a highly effective treatment. The consequences for this individual were profound and he is now suing the NHS and his neurologist for loss of earnings. 

The main purpose of the meeting is to review the evidence for treating MS early and effectively, i.e. applying all the management and treatment principles captured in our 'Brain Health: Time Matters in MS' policy document. The real value of this meeting for HCPs is not DrK and myself discussing the scientific or medical rationale for this strategy, but the legal perspective, in particular, the variance is MSology practice. When do you become an outlier, either an under-treater or an over-treater, and when do you expose yourself to a legal challenge from your patients?

If you are a card-carrying HCP you are welcome to attend. Due to ABPI rules, MSers can't attend.  Tickets are limited and are being allocated on a first come first serve basis.  


THE EMBEDDED INVITATION HAS HAD TO BE REMOVED AS IT IS FOR HEALTH CARE PROFESSIONAL EYES ONLY. 

IT IS  QUITE AMAZING BUT THE ABPI GUIDELINES DON'T ALLOW PHARMA TO COMMUNICATE WITH PEOPLE WHO HAVE MS DIRECTLY. 

IF YOU ARE AN HCP AND NEED MORE INFORMATION PLEASE CONTACT ME BY EMAIL. THANK YOU.

ProfG    

Walking-the-talk or not-walking-the-talk

You may know by now that 'The Dream Team' completed the 3-peaks challenge in less than 24-hours yesterday. Well done. Their aim was to raise more than £5,000 for the MS Society. The MS Society is a remarkable organisation; an organisation the wider MS community could not manage without. They not only look after their members locally but take on very important national tasks such as lobbying, advocacy, education, setting the research agenda and supporting research. The MS Society, therefore, needs your support. If you haven't done so already can you please help and make a small donation, it would be greatly appreciated? 

The Dream Team

Sunday, 24 June 2018

Stornoway research day series: Vitamin D

Dr Stewart Webb talks about Vitamin D and its role in multiple sclerosis. He discusses bone health, falls and fractures.





Saturday, 23 June 2018

MS Dream Team are on their way!


The team arrived in one piece at Fort William (the home of the tallest peak in Scotland: Ben Nevis) just shy of midnight yesterday. This morning we’ve packed and re-packed our bags, tried out our UK MS Society t-shirts (some of us need to lose weight...), and are deligently checking the weather hour to hour for a wee glimpse of the sun. Scotland even at her worst is simply breathtaking.

Driving up last night, we witnessed rows of white vans passing us in the opposite direction at 11pm and immediately knew that the first few teams have managed to scale Ben Nevis in 5 hours. Those of you’ve who have been up Ben Nevis will already know that a tourist is quoted 7 hours by the locals. Fingers crossed that we achieve a quick time today. From Ben Nevis, we will drive to the Lakes to scale Scafell Pike in the dark and then onto Wales to climb Snowdon. Our goal is to achieve all of this in 24 hours.

When I started the team, the participants were hand picked for their dedication to Multiple Sclerosis work and the rare disorders, and it goes without saying that they also have superb fitness levels. Everything you’ll see on our Just Giving page and Twitter (@neurognanapavan) gives a good indication of our efforts to organise this challenge. The first training events began 4 months ago, and all the logistics of the challenge have been self-organised (we decided as a team that we will not use one of the commercial companies for this). There have been ups and down and owing to medical issues and scope of the endeavour we currently stand at 4 members (outlined below).


  • Professor Alasdair Coles (Professor of Neurology, Cambridge).
  • Dr Emre Amirak (Associate Medical Director in pharma, ex-cardiothoracic surgeon).
  • Dr Violeta Sanchez (Consultant Neurologist, Barts Health)
  • Dr Sharmilee Gnanapavan (Consultant Neurologist, Barts Health)

Our families and friends have listened to us at ad nauseam about this day, some of it with reservations but ultimately they understand that what makes us persistent in our obstinacy at work, is also driving this. So hear’s to the #MSDreamTeam a partnership made in common goals and a start of a good friendship.

Stornoway research day: What does the future hold?

Prof G discusses upcoming treatments for progressive MS and the importance of maintaining brain health and upper limb function. 



Friday, 22 June 2018