The following presentation was from Joela Matthews our neuroscience pharmacist to the neurology trainees on Wednesday.
Category: Politics, campaigns and information
The next generation
Training the next generation of MSologists is one of my priorities.
I helped arrange and teach on the Pan-London Calman Specialist Registrar (SpR) teaching day yesterday. It was great to see so many young trainee neurologists attending; thank you. And to the speakers for giving up their time to teach and inspire the next generation of neurologists to become MSologists; thank you.
I hope you all enjoyed the day the following is the programme.
I was impressed by the level of engagement of the audience. I was particularly happy with an insight from one of the trainees who suggested we should be managing MS they way rheumatologists manage RA; i.e. early and aggressively. This was music to my ears. I have been pushing the treat-2-target RA paradigm for MS for several years now. The only difference is that our treatment targets have gradually become more ambitious as we have moved from NEDA-1 (relapses) to NEDA-3 (MRI activity) to preventing end-organ damage as measured with MRI (normalising the rate of brain volume loss or NEDA-4) and normalising CSF and blood neurofilament levels (NEDA-5) and beyond. What I mean by beyond is that our ultimate aim is to cure people of having MS and to allow them to get to old age with as much brain as possible. Is this too ambitious?
The following is my presentation from yesterday that can be downloaded from my slideshare site.
At the end of my session, we got into a lively debate about whether or not everyone with MS needs to be treated. Obviously not, based on my presentation only people with active MS are eligible for treatment. Those who have inactive MS cannot be treated under current NHS England guidelines and if they remain inactive they will hopefully end-up having benign MS. Surely the aim of our treatments is to convert everyone with MS into having inactive MS that will hopefully turn out to be benign MS after 25-30 years of follow-up. What we did not cover in this mini-debate is what is active MS? Should it include smouldering MS?
If any of the trainees are reading this post can I please recommend that you read the following posts I have recently done and to bookmark my MS-Selfie site that is still under development.
Posts of potential interest:
What the eye doesn’t see?
I saw someone with possible MS earlier this week and he had been told that he couldn’t have MS because he only had one detectable lesion on his MRI. Is this correct?
Focal demyelinated plaques in white matter, which are the hallmark of multiple sclerosis pathology, only partially explain the patient’s clinical deficits. We thus analysed global brain pathology in multiple sclerosis, focusing on the normal-appearing white matter (NAWM) and the cortex. Autopsy tissue from 52 multiple sclerosis patients (acute, relapsing-remitting, primary and secondary progressive multiple sclerosis) and from 30 controls was analysed using quantitative morphological techniques. New and active focal inflammatory demyelinating lesions in the white matter were mainly present in patients with acute and relapsing multiple sclerosis, while diffuse injury of the NAWM and cortical demyelination were characteristic hallmarks of primary and secondary progressive multiple sclerosis. Cortical demyelination and injury of the NAWM, reflected by diffuse axonal injury with profound microglia activation, occurred on the background of a global inflammatory response in the whole brain and meninges. There was only a marginal correlation between focal lesion load in the white matter and diffuse white matter injury, or cortical pathology, respectively. Our data suggest that multiple sclerosis starts as a focal inflammatory disease of the CNS, which gives rise to circumscribed demyelinated plaques in the white matter. With chronicity, diffuse inflammation accumulates throughout the whole brain, and is associated with slowly progressive axonal injury in the NAWM and cortical demyelination.
The problem: ‘MS has become an MRIscopic disease’.
The diagnosis of MS remains clinical and is underpinned by the need to show (1) dissemination in time (typically new activity 4 weeks apart or the presence of locally produced oligoclonal IgG bands in the spinal fluid) and (2) dissemination is space (symptoms and/or signs affecting two different pathways in the CNS) and (3) the exclusion of other possible diagnoses. It is clear that based on these criteria you don’t necessarily need to have visible, or specific, MRI lesions to make a diagnosis of MS. However, neurologists feel uncomfortable making a diagnosis of MS or CIS if there are no visible lesions on MRI. In other words from a practical and clinical perspective, MS has become a macroscopic or MRIscopic disease. Therein lies the rub.
MS is a biological disease that is characterised pathologically by multifocal inflammatory lesions that cause demyelination and variable degrees of axonal loss. Please note I have dropped using the term white matter. MS is clearly both a white and grey matter disease with more than half the lesion burden in the largely MRI-lesion-invisible grey matter component (see study below). Even in the white matter where it is easier to see lesions the resolution of an MRI scan is down to about 3-4 mm. Many more lesions are found pathologically than what is seen on MRI or the naked eye. Therefore, particularly early on in the course of the disease, there will be a small number of people with MS with one or no lesions who have MS.
A very small lesion in a strategic pathway can cause typical symptoms and signs, but when you investigate many of these patients with an MRI scan you see no obvious lesion in the expected area. This happens more often than not with a so-called internuclear ophthalmoplegia (INO); a very specific eye movement problem that presents with double-vision on looking to the left or right. This is an example of a microscopic lesion causing an MS attack. This is why we shouldn’t be using MRI to confirm, or make, a diagnosis of relapse in pwMS.
The study below that is rapidly becoming a citation classic in the field of MS, shows you with elegant infographics how large the lesion burden is in areas that are MRI invisible using our standard clinical sequences.
Kutzelnigg et al. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain. 2005 Nov;128(Pt 11):2705-12.
Focal demyelinated plaques in white matter, which are the hallmark of multiple sclerosis pathology, only partially explain the patient’s clinical deficits. We thus analysed global brain pathology in multiple sclerosis, focusing on the normal-appearing white matter (NAWM) and the cortex. Autopsy tissue from 52 multiple sclerosis patients (acute, relapsing-remitting, primary and secondary progressive multiple sclerosis) and from 30 controls was analysed using quantitative morphological techniques. New and active focal inflammatory demyelinating lesions in the white matter were mainly present in patients with acute and relapsing multiple sclerosis, while diffuse injury of the NAWM and cortical demyelination were characteristic hallmarks of primary and secondary progressive multiple sclerosis. Cortical demyelination and injury of the NAWM, reflected by diffuse axonal injury with profound microglia activation, occurred on the background of a global inflammatory response in the whole brain and meninges. There was only a marginal correlation between focal lesion load in the white matter and diffuse white matter injury, or cortical pathology, respectively. Our data suggest that multiple sclerosis starts as a focal inflammatory disease of the CNS, which gives rise to circumscribed demyelinated plaques in the white matter. With chronicity, diffuse inflammation accumulates throughout the whole brain, and is associated with slowly progressive axonal injury in the NAWM and cortical demyelination.
MMR to test or not to test?
Can I assume you know about Andrew Wakefield and the fake link between the MMR vaccine and autism?
The number of children receiving the MMR vaccine in England is falling. A report from NHS Digital shows that coverage of the MMR vaccine for children reaching their 2nd birthday has fallen the fourth successive year. Uptake was 91.2% in England in 2017-18, down from 91.6% in 2016-17 and the lowest level since 2011-12 (BMJ). The downside of this is that we have seen an epidemic of measles, yes measles, in the UK. Between 1 January 2018 and 31 October 2018, there have been 913 laboratory-confirmed measles cases in England (Public Health England).
Despite Wakefield being discredited and struck off the medical register in the UK he, and the ‘Anti-Vax’ brigade, is still having a profound impact on society, which is gradually beginning to filter down to how we manage MS. Why?
The number of children receiving the MMR vaccine in England is falling. A report from NHS Digital shows that coverage of the MMR vaccine for children reaching their 2nd birthday has fallen the fourth successive year. Uptake was 91.2% in England in 2017-18, down from 91.6% in 2016-17 and the lowest level since 2011-12 (BMJ). The downside of this is that we have seen an epidemic of measles, yes measles, in the UK. Between 1 January 2018 and 31 October 2018, there have been 913 laboratory-confirmed measles cases in England (Public Health England).
So what has this got to do with MS? Well, unvaccinated people also get MS. If you are unvaccinated and have not been exposed to the wild virus you are at risk of acquiring these infections as an adult. If you then decide to go onto longterm immunosuppression to treat your MS you are putting yourself at risk of serious complications from these infections. In addition, once you are on a longterm immunosuppressive therapy you can’t be vaccinated with the MMR vaccine as it is a live attenuated vaccine.
Because of this, we will be starting to screen all our patients at baseline, i.e. before initiating a maintenance immunosuppressive therapy, to make sure they have immunity to MMR. If they are antibody negative we will be offering them the option of receiving the MMR or the individual components to make sure they are immune to these viruses. This practice is not new. When I was in Melbourne last year, where MMR antibody screening has been routine for several years, they had picked-up three pwMS who were MMR-negative in the last year. At our recent ABN conference in Birmingham, there was a presentation of a young woman who tragically died of inclusion-body encephalitis due to measles (please note she did not have MS). Tragically, her mother had stopped her having the MMR vaccine as a child.
If you are an HCP prescribing DMTs do you want any of your patients to develop inclusion-body encephalitis on fingolimod, DMF, natalizumab, alemtuzumab, cladribine or ocrelizumab? Definitely not as it is a preventable infection.
I also need to walk the talk. With my #PreventMS hat on and one of our strategies being an EBV vaccine to prevent MS, I have to support and promote vaccination as a very important public health initiative. This is why I urge you to read this week’s ‘5 minutes with…Peter Hotez‘ from the BMJ.
Sophie Arie: Speaking up for vaccination: five minutes with…Peter Hotez. BMJ 2018.
Excerpt:
The professor and dean of the National School of Tropical Medicine at Baylor College of Medicine, in Texas, explains to Sophie Arie why he’s written a book about his daughter
“I became alarmed at the sharp drops in vaccine coverage. Children are now dying because of the “anti-vax” movement. Most of the children who died in the latest influenza epidemic in the US weren’t vaccinated.
“The anti-vax movement is extremely well organised, with huge funding and bandwidth. There are 480 anti-vaccine websites. Of course, people are challenging their paediatricians because of what they’ve read.
“But there is general silence on the pro-vaccine side. The US government has been conspicuously silent. Unicef and the World Health Organization are not recognising the threat this poses to low and middle-income countries.
“We have enabled this by refusing to recognise that public engagement is important for scientists. When I was doing my training the message was ‘you’re not supposed to engage the public.’ It was seen as self-promotion. It may be that it’s just not in the DNA of our profession. But if you are silent you won’t achieve your goals. We have to speak up.
“I’ve written my book, Vaccines Did Not Cause Rachel’s Autism, as a vaccine scientist, a paediatrician, and an autism dad. I’ve just spoken in simple, declarative language which is not what we scientists are taught to do. I’ve written about my personal experience and I’ve just said, ‘vaccines don’t cause autism’ and here’s why. The Institute of Medicine would say something like ‘the preponderance of evidence today cannot show any clear link between vaccines and autism.’ That sounds to a layperson like hedging.
“I’m hoping it can make as much difference as a book can make for parents who are sitting on the fence, for paediatricians who are feeling under siege, and journalists who still frame this as a ‘debate’ when there is no debate.
“Colleagues are supporting me privately but not speaking out themselves. The anti-vax movement is very aggressive. Who wants to receive an email while standing in line for their morning bagel to find themselves being compared to Hitler? It’s not very nice.
“We need to give physicians and scientists the tools and training to communicate. It’s good that some grants for funding now demand that you provide an advocacy plan for your science. This needs to become part of the way we think.”
CoI: multiple
Should we deny non-whites access to DMTs?
A question about whether or not currently licensed DMTs are effective in African-Americans has arisen. Why?
Lack of evidence does not mean lack of efficacy.
If you are a non-Caucasian pwMS you will become disabled quicker than your Caucasian counterparts. The evidence that so-called ‘non-whites’, which includes African-Americans, Africans and Asian do worse than ‘whites’ is pretty well accepted. However, most of this data was derived from the pre-DMT and 1st-generation, or injectable (IFNbeta and GA), DMT eras. The question of whether or not the same now holds true in the post-Natalizumab era is unclear.
Jagannadha Avasarala suggests in an editorial below that we should question the assumption that licensed DMTs work in these populations because we don’t have the necessary data to support our assumptions. Why? Simply, because there are too few African-Americans, Africans and Asians in the pivotal phase 3 trials to do sub-group analyses and answer the question he has proposed (see OPERA I & II data below).
These issues also apply to paediatric or childhood MS. In response to the latter, the FDA and EMA now mandate as part of the licensing process that Pharma have to do paediatric trials as part of their post-marketing commitments. Should the regulators be doing the same for the ethnic minority groups? Maybe, but this would come at a cost. Post-marketing commitments are expensive and their costs are built into the drug pricing. Do we want more expensive DMTs? A better solution would be to rely on real-world evidence collected in a systematic way via national and regional registers. I have little doubt that registry data will be able to tell us if ‘non-white’ pwMS respond or not to DMTs.
This editorial will not change our practice. We treat people with active MS who are from ethnic minorities in the same way we treat Caucasian pwMS. Why wouldn’t we? Lack of evidence does not mean lack of efficacy. In my experience pwMS who are from an ethnic minority background respond as well to high efficacy DMTs in terms of treating-2-target of NEDA than Caucasian pwMS. What tends to happen is that they are more likely to end up at the top of the treatment pyramid on one of the monoclonals. The reason for this is that they probably need these higher efficacy DMTs because they have more active MS. Should we rely on anecdotes? Probably not, I suggest we and others audit our data and get back to you on this specific question.
Avasarala. FDA-approved drugs for multiple sclerosis have no efficacy or disability data in non-Caucasian patients. CNS Spectr. 2019 Jan 3:1-2. doi: 10.1017/S1092852918001517.
Pharmacotherapy of multiple sclerosis (MS) is evolving rapidly. Despite impressive gains over the past 2 decades in the approval of multiple drugs for MS, lack of recruitment of minorities with MS in phase 3 clinical studies is a persistent concern and skews efficacy and disability data.
CoI: multiple
I am alone and feeling vulnerable
Did you know that 3 out of 5 pwMS self-report being lonely? Why?
The following study explores the possible causes of loneliness.
As you know MS is a very stigmatizing disease that given sufficient time, at least in the preDMT era, causes most pwMS to become disabled. Associated with the disability is well-documented unemployment, the breakdown in personal relationships, depression, anxiety, cognitive impairment, fatigue and loss of quality of life. As a result of these impacts of MS, pwMS become socially isolated and lonely.
This study below confirms these facts and shows that loneliness can be explained by employment status, marital status, upper extremity function (#ThinkHand), social disability (#ThinkSoical) and physical disability. Not surprising other correlates included depression, cognitive fatigue (#ThinkCognition), psychosocial fatigue and quality of life.
What we now need to do is learn from this and do something about it. That is why we are trying to set-up a programme of local MS wellness champions to try and tackle this problem. In fact, I am meeting with Alyson McGregor, the National Director of ‘Altogether Better‘, this afternoon to ask her to help us with our social capital project. I am sure we can model our #PatientActivation programme on their ‘Altogether Better Health Champions‘ model and achieve similar outcomes.
I said yesterday I provisionally called the programme ‘Teaching MSers how to Fish’. This title is based on the teachings of Lao Tzu, the Chinese philosopher and founder of Taoism, who said “Give a man a fish and you feed him for a day. Teach him how to fish and you feed him for a lifetime”.
Balto et al. Loneliness in Multiple Sclerosis: Possible Antecedents and Correlates. Rehabil Nurs. 2019 Jan/Feb;44(1):52-59.
DESIGN: Cross-sectional, comparative study of MS (n = 63) and healthy adults (n = 21).
METHODS: Data were collected using self-reports of loneliness and antecedents and correlates and analyzed using inferential statistics.
FINDINGS: Those with MS had significantly higher loneliness scores than healthy adults (p < .05), and this was explained by employment status. Possible antecedents included marital status (p < .05), upper extremity function (r= -.28, p < .03), social disability frequency (r= -.49, p < .00), social disability limitations (r= -.38, p < .00), and personal disability limitations (r= -.29, p < .03). Social disability frequency (beta = -.41, p < .001) and marital status (beta = -.23, p < .046) accounted for 25% of the variance in loneliness scores. Possible correlates included depression (r= .49, p < .00), cognitive fatigue (r= .34, p < .01), psychosocial fatigue (r= .30, p < .02), and psychological quality of life (r= .44, p < .00).
CONCLUSIONS: We provide evidence of loneliness in persons with MS, and this is associated with possible antecedents (e.g., marital status and disability limitations) and correlates (e.g., depression and fatigue).
CLINICAL RELEVANCE: Loneliness should be recognized clinically as an important concomitant of MS.
I am aware the killjoys reading this post will poo-poo these ideas, but before doing this please think about what it must be like to wake each day alone, and possibly disabled, and to go to bed each night alone, knowing that tomorrow is likely to be a repeat of today.
Balto et al. Loneliness in Multiple Sclerosis: Possible Antecedents and Correlates. Rehabil Nurs. 2019 Jan/Feb;44(1):52-59.
PURPOSE: The prevalence and possible antecedents and correlates of loneliness in multiple sclerosis (MS) was examined.
DESIGN: Cross-sectional, comparative study of MS (n = 63) and healthy adults (n = 21).
METHODS: Data were collected using self-reports of loneliness and antecedents and correlates and analyzed using inferential statistics.
FINDINGS: Those with MS had significantly higher loneliness scores than healthy adults (p < .05), and this was explained by employment status. Possible antecedents included marital status (p < .05), upper extremity function (r= -.28, p < .03), social disability frequency (r= -.49, p < .00), social disability limitations (r= -.38, p < .00), and personal disability limitations (r= -.29, p < .03). Social disability frequency (beta = -.41, p < .001) and marital status (beta = -.23, p < .046) accounted for 25% of the variance in loneliness scores. Possible correlates included depression (r= .49, p < .00), cognitive fatigue (r= .34, p < .01), psychosocial fatigue (r= .30, p < .02), and psychological quality of life (r= .44, p < .00).
CONCLUSIONS: We provide evidence of loneliness in persons with MS, and this is associated with possible antecedents (e.g., marital status and disability limitations) and correlates (e.g., depression and fatigue).
CLINICAL RELEVANCE: Loneliness should be recognized clinically as an important concomitant of MS.
Happy New Year: some reflections on 2018
Happy New Year! In response to a comment yesterday I produced the following overview of some of Barts-MS’ activities for 2018. It makes me very proud to be part of the team and I would like to thank them all for all their hard work and perseverance.
I would like to think of 2018 as the year of the #HashTag.
Some of our long-running social media campaigns have started to deliver returns on the time and effort that have gone into them. All of these have been linked to a particular #HashTag.
In short Barts-MS’ 2018 activities can be classified into five categories which are research, services, policy, education and PPI (patient-public involvement).
1. Research
#ThinkHand – We continued to make a strong case for our #ThinkHand campaign with numerous research outputs. These are all being used to support further work in this area. I am the principal investigator for ORATORIO-HAND a phase-3b study of ocrelizumab in PPMS that will include patients with an EDSS of up to 8.0. The primary outcome is the 9-HPT. In parallel, DrK has been working hard to get an NIHR funded trial off the ground called CHARIOT-MS. DrK has shepherded the grant through round 1 and is waiting to hear whether or not the study will get funded. CHARIOT-MS is a study of oral cladribine in advanced MS targeting both SPMS and PPMS with the primary outcome being the 9HPT. If there is one person in our group who deserves an award for resilience and perseverance it is DrK; he has doggedly stuck to the task. There will be much celebration at Barts-MS if he gets his just rewards for all his hard work over the last few years. More importantly, CHARIOT-MS will become a beacon of hope for people with advanced MS.
#SelfMonitoring – Nicholas Dubuisson completed a herculean meta-analysis to analyse inclusion criteria used for progressive MS trials. In summary, it shows what a mess the field is in when it comes to identifying who is worsening or progressing prior to being recruited into progressive clinical trials. We have used this meta-analysis to make the case for using self-monitoring to document worsening in the 12-24 month prior to trial recruitment. In response to this, we have been gradually building our suite of online web apps to empower and activate the MS community to do just this.
#under&over – Alison our design researcher developed a hand and upper limb rehabilitation tool called under&over, which was launched at ECTRIMS2018 in Berlin. Alison has been successful in getting a grant to test whether or not under&over will work as a remote rehab tool.
#ThinkCognition – I have been pushing the concept of MS being a preventable dementia for several years and that by focusing on cognition early on in the course of the disease we would get the MS community to adopt the early-effective treatment paradigm. One hypothesis that I proposed several years ago came to fruition this year; i.e. that pwMS who are able to learn on a cognitive test do better than poor-learners. This analysis was done with Maria-Pia Sormani using the combined FREEDOMS fingolimod data set.
#ThinkSocial – You will notice some early activity from our group on social capital as a potential predictor of outcomes in pwMS. We have been very fortunate to have Saul Reyes a Colombian neurologist join us an ECTRIMS fellow for one year. Saul will be studying social capital in MS. The other excellent news is that the Horne Family Foundation has awarded us a grant to study whether or not our PPI programme increases social capital and if it does will this increase the quality of life of pwMS and reduced healthcare utilization. Ultimately, we want to be able to do long-term studies to assess whether or not increasing social capital improves outcomes for pwMS. An interesting point worth noting is that the UK government has just appointed a loneliness minister to address social isolation at a population level. I interpret this as a sign that our #ThinkSocial campaign is of the moment.
#PreventMS – The MouseDoctor and I left Queen Square to move to Barts and The London School of Medicine and Dentistry (Queen Mary University of London) in 2006. One of the main drivers for me personally was to shift my long-term research focus on MS prevention. This year saw the activation of a priming grant to set-up a Preventive Neurology Unit that includes a group working on MS. We were able to get Dr Ruth Dobson back to QMUL to lead the MS Prevention programme. We have a lot of activities planned under this banner for 2019 and beyond. We will keep you posted on developments in this space, but you can get the gist of things to come from our recent blog posts on ‘proving EBV is the cause of MS’ and ‘Why do I have MS?.. Because you have a common virus?’.
#CharcotProject – We finally got publish the results of INSPIRE trial and our #CrowdaCure EBV saliva shedding project. The saliva data has been instrumental for powering our FamV study, which we hope to start in the next few months. Please note the contrary to some commentators the #CharcotProject is alive and kicking.
2. Services
#OffLabel – We published our own experience with using off-label subcutaneous cladribine in MS and provided anecdotal evidence, using case studies, that it will work in people with more advanced MS. The latter has been vital in supporting our CHARIOT-MS grant application. Whether or not these publications will get other centres in the UK and other countries to follow our lead is a moot point. Interestingly, we have had a few centres requesting our off-label protocol so there may be the gradual rumblings of an off-label movement starting.
#AtraumaticLP – We continue to promote using lumbar punctures and CSF analysis to monitor MS. Central to this is our LP service that now only uses atraumatic or non-cutting needles to reduce the complications of LPs in particular post-LP headaches.
#EndOrganDamage – Our lab service measuring CSF neurofilament levels more than trebled last year. Sharmilee and Lucia have done a remarkable job. At least four other UK centres are regularly requesting CSF NFL levels via our laboratory. We also have the peripheral blood assay working and are part of an International consortium to validate the assay. I suspect we may move from CSF to peripheral blood monitoring very soon.
#NAbs – We are in the process of validating our anti-alemtuzumab and other anti-drug antibody assays. We know NAbs are an important issue and explain why some pwMS fail to respond to biological therapies. NAbs, in particular, those targeting alemtuzumab, are also a window into the immunology of the drug and may be telling us why pwMS treated with alemtuzumab get so many secondary autoimmune diseases. Watch this space!
3. Policy
#OffLabel & #EssentialMedicine – In 2014 whilst I was on my 6-month sabbatical we formulated the Barts-MS Essential Off-label DMT list. This was to address limited access to DMTs in resource-poor countries. Off-label subcutaneous cladribine is one of the drugs on this list. We soon realised that trying to sort out access to essential medication was a problem and task too big for Barts-MS. I was fortunate to be invited to present some of our ideas to the board of the MSIF in 2015 and as some of our ideas dovetailed with their 5-year strategy they were able to take up the challenge. I was honoured and privileged to be asked to co-chair the MSIF’s WHO Essential Medicines panel with Brenda Banwell and to help prepare and submit a proposal to the WHO to get a limited number of DMTs on the WHO Essential Medicines List. We successfully submitted an application in early December. This was a mammoth task as it involved many different stakeholders and I want to thank the MSIF for making this a reality. Fingers-crossed!
#BrainHealth – Our Brain Health initiative turned three last year. We have continued to promote #BrainHeallth awareness in the 3-years since we launched the original policy document at ECTRIMS-2015 in Barcelona. However, as information is not sufficient to change behaviour we made progress in developing our international quality standards and have piloted them in three countries. In 2019 we will be focusing on disseminating the quality improvement tool and developing a #PatientActivation programme.
#Women4MS – In collaboration with Alasdair Coles, we highlighted the inequities in relation to women at the top table in the field of MS. Our blog posts and subsequent publication has set off a chain reaction and a response letter by female academics, who make the point that gender inequality occurs despite the availability of a substantial number of successful senior female academic neurologists and neuroscientists worldwide. DrRuth and her team have done some data trawling to highlight the problem further and these data will be published later this year.
#Run4MS – This is an initiative using parkrun programme to get pwMS and HCPs more active. #Run4MS is an ambitious, but important, initiative and is being run by the MS Trust.
#MS_is_1_and_not_2_or_3_diseases – We have continued to challenge the current dogma and promote MS as being one disease.
4. Education
#MSPreceptorship – We continue to run our MS Preceptorships that are designed to teach people about MS and the modern management of the disease.
#MSAcademy – I am the director of the MS Academy. This programme has expanded and included a meeting to tackle variance in the provision of MS Services in the UK. If you want to participate in the MS Academy please register for one of the upcoming courses.
#MS@TheLimits – I co-chaired our second MS@TheLimits meeting in London in November. Feedback from the delegates was remarkably good and we will endeavour to make this an annual event. For those of you who are interested, all the talks are now online, including Prof G taking a battering in a debate. To be fair I had to prepare my arguments in a few hours on the day of the debate as one of our debaters had to pull out at short notice.
#triMS-Online – We finally managed to get our virtual online conference started. Our first event was very well received and addressed all our objectives. The idea for this meeting was germinated and developed on this blog; so thank you. Who said social media was a one-way street? We learn as much from you as you learn from us. Please note that more than half of the steering committee of triMS.online are women and it includes many young people from all over the world; this is no accident.
#ECTRIMS2018 – We hosted a #ClinicSpeak stand at ECTRIMS; this year with a focus on #SelfMonitoring. The MouseDoctor and Sharmilee did their annual MS Hangout that is a real hoot and worth watching. We also arranged and ran the annual ECTRIMS Burning Debate. The motion debated was “The new McDonald diagnostic criteria make them difficult to use in clinical practice”. This year it was an all female event, which was to compensate for the all-male affair in 2017.
#MSFellowships – We continue to encourage and accept young trainees to our centre. This year was no exception and included a very bright and energetic Erasmus exchange student.
5. Patient-public Involvement or PPI
#DigestingScience – Alison and her team have continued to disseminate her Digesting Science programme in the UK and globally. The Digesting Science packs have been translated into two other languages. As this programme targets children of pwMS, we will be embedding it our PPI programme for #PreventMS going forward.
#ResearchDay – This year we decided to take our research day to the Hebrides and had a very successful meeting in Stornoway. The Stornoway talks are all online. Unfortunately, the London MS Research Day didn’t happen for a second year in a row. We need to do something about it. Any suggestions?
#ResearchBlog & #SocialMedia – We continue to run our blog with almost daily postings. I took a break from the blog to focus on grant writing but will make an effort in 2019 to post more frequently. I increased my social media activity to try and compensate, but there is not much you can say in 280 characters, which is not ideal
#ThinkHand – We held a very successful #ThinkHand event in London in Feb last year to celebrate hand function in pwMS. Our #ThinkHand event was bigger than simply an awareness campaign and we managed to get wider media coverage and bring several important stakeholders on board to support #Chariot-MS
What about 2019 and beyond?
The above summary is only a brief overview of some of #BartsMS’ activities in 2018. The list is not exhaustive but does give you an idea of what we are trying to achieve. 2019 will be more of the same, with an emphasis on the following #HashTags:
#ThinkHand
#ChariotMS
#OffLabel
#ThinkCognition
#ThinkSocial
#ThinkSequential
#AttackMS
#ThinkCombination
#PreventMS
#Women4MS
#Run4MS
#Walk4MS
#PlasmaCells
#Neuroprotection
#ThinkCure
#DietSpeak
CoI: multiple
#ThinkHand – taking telerehabilitation one step further
What does 2019 hold for the various Barts-MS campaigns?
We are continuing to make the case for our #ThinkHand campaign with several outputs in 2018, which are being used to support our work in this area. I am very proud that ORATORIO-HAND, a phase-3b study of ocrelizumab in PPMS, which will include patients with an EDSS of up to 8.0 and will start recruiting in the first quarter of 2019. The primary outcome in ORATORIO-HAND is the 9-HPT; this in itself is a first and a major milestone for the field of MS.
In parallel, DrK has been working very hard to get his NIHR funded trial off the ground called CHARIOT-MS. DrK’s perseverance has gotten the study through round 1 of peer-review and we are now waiting to hear whether or not the study will get funded. CHARIOT-MS is a study of oral cladribine in advanced MS will target both SPMS and PPMS up to an EDSS of 8.5 and again the primary outcome will be the 9HPT.
These two studies are remarkable for several reasons. Firstly, these trials are challenging the dogma that MS is not modifiable beyond EDSS 7.0, secondly, it is shifting the focus away from the lower limbs and EDSS to a new primary outcome the 9-HPT and, finally, it is giving people with advanced MS hope in valuing their hand function and independence.
These two studies are remarkable for several reasons. Firstly, these trials are challenging the dogma that MS is not modifiable beyond EDSS 7.0, secondly, it is shifting the focus away from the lower limbs and EDSS to a new primary outcome the 9-HPT and, finally, it is giving people with advanced MS hope in valuing their hand function and independence.
As part of our #ThinkHand campaign Alison Thomson, our research designer, in collaboration with the Agency of Design, helped design an upper limb rehabilitation tool called under&over, which we launched at ECTRIMS-2018 in Berlin. We have now been successful in obtaining a grant to test whether or not under&over will work as a rehab tool and are planning a remote web-based study to test it. Again our primary outcome will be stabilisation, or improvement, in the performance of the 9HPT only this time we will be using our cardboard 9HPT.
Interestingly the telerehabilitation study below showed that remote rehab can work. I see no reason why a web-based rehab programme won’t work either. We will obviously keep you posted on this study, we may even be given permission from the ethics committee to recruit via our blog.
Would you be interested in helping us design the study and/or participating?
Would you be interested in helping us design the study and/or participating?
Fjeldstad-Pardo et al. Telerehabilitation in Multiple Sclerosis: Results of a Randomized Feasibility and Efficacy Pilot Study. Int J Telerehabil. 2018 Dec 11;10(2):55-64.
A prospective, randomized, three-arm, evaluator blinded study to demonstrate the feasibility of a telerehabilitation (TR) program in individuals with ambulatory deficits secondary to Multiple Sclerosis (MS) and evaluate its efficacy when compared to conventional on-site physical therapy (PT) was completed. Thirty participants were evaluated at baseline and randomized to one of three groups with intervention lasting 8 weeks: Group 1 (control)- customized unsupervised home-based exercise program (HEP) 5 days a week; Group 2 (TR)- remote PT supervised via audio/visual real-time telecommunication twice weekly; Group 3 (PT)- in-person PT at the medical facility twice weekly. Outcomes included patient reported outcomes (PROs) obtained through questionnaires, and measurements of gait and balance performed with bedside tests and a computerized system. Functional gait assessment improved from baseline in all three groups. There were no significant differences between the TR and the conventional PT groups for a variety of outcome measures. TR is a feasible method to perform PT in persons with MS and has comparable efficacy to conventional in-person PT as measured by patient reported outcomes and objective outcomes of gait and balance.
CoI: The design, development and manufacture of the under&over rehab tool and the follow-on web-based rehab study has been kindly funded by unrestricted grants from F. Hoffmann-La Roche AG.
A prospective, randomized, three-arm, evaluator blinded study to demonstrate the feasibility of a telerehabilitation (TR) program in individuals with ambulatory deficits secondary to Multiple Sclerosis (MS) and evaluate its efficacy when compared to conventional on-site physical therapy (PT) was completed. Thirty participants were evaluated at baseline and randomized to one of three groups with intervention lasting 8 weeks: Group 1 (control)- customized unsupervised home-based exercise program (HEP) 5 days a week; Group 2 (TR)- remote PT supervised via audio/visual real-time telecommunication twice weekly; Group 3 (PT)- in-person PT at the medical facility twice weekly. Outcomes included patient reported outcomes (PROs) obtained through questionnaires, and measurements of gait and balance performed with bedside tests and a computerized system. Functional gait assessment improved from baseline in all three groups. There were no significant differences between the TR and the conventional PT groups for a variety of outcome measures. TR is a feasible method to perform PT in persons with MS and has comparable efficacy to conventional in-person PT as measured by patient reported outcomes and objective outcomes of gait and balance.
CoI: The design, development and manufacture of the under&over rehab tool and the follow-on web-based rehab study has been kindly funded by unrestricted grants from F. Hoffmann-La Roche AG.
Who won the RIS debate?
Merry Christmas
Christmas is a time for reflection and to spend it with friends and family.
#ThinkSocial
I went for a long run yesterday that allowed me to reflect on a good year for Barts-MS and for people living with multiple sclerosis (pwMS). We are making unprecedented advances in the treatment of MS. PwMS are being diagnosed earlier, treated earlier and are less disabled than before. We are seeing a drop off in the number of pwMS entering the so-called secondary progressive stage of the disease, i.e. less walking sticks and fewer wheelchairs.
Despite these incredible advances, there are a lot of people who have missed the boat and have had their lives turned upside down by MS. We know MS is a very stigmatizing disease and leads to social isolation and loneliness. A recent study showed that 3 out of 5 pwMS described themselves as being lonely. If you know someone with MS, please pick-up the phone and call them and have a chat. Visit them and/or make arrangements to take them for a walk. Socialise and make them feel loved and wanted. Christmas is a time for sharing and being together.
Twenty-nineteen is going to be the year of thinking social (#ThinkSocial). We are launching several initiatives and research projects exploring how we can ‘maximise’ and ‘expand’ the social capital of pwMS. I am convinced that pwMS who have large social networks do better than pwMS who don’t.
Twas the night
Before Christmas
When all through the house
Not a creature was stirring
Not even a mouse
The stockings all hung
By the chimney with care
In hopes
That St. Nicholas
Soon would be there
The children were nestled
All safe in their beds
While visions of sugarplums
Danced in their heads
And mom in her kerchief
And I in my cap,
Had just settled down
For a long winter’s nap
When out on the lawn
There arose such a clatter
I sprang from my bed
To see what was the matter
Away to the window
I flew like a flash
Tore open the shutters
And threw up the sash
The moon on the breast
Of the new fallen snow
Gave the lustre
Of midday
To object below
When what
To my wandering eyes
Should appear
But a miniature sleigh
And eight tiny reindeer
With a little ol driver
So lively and quick
I knew in a moment
It must be St. Nick
More rapid than eagles
His courses they came
As he whistled
And shouted
And called
Them by name
Now dasher
Now dancer
Now prancer
Now vixen
On Comet
On Cupid
On Donder
An Blitzen
To the top
Of the porch
To the top
Of the wall
Now dash-away
Dash-away
Dash-away all
As dry leaves
Before the wild
Hurricane fly
When they meet
With an obstacle
Mount to the sky
So up
To the housetop
The courses
They flew
With a sleigh
Full of toys
And St. Nicholas too
And then
In a twinkling
I heard on the roof
The prancing
And pawing
Of each little hoof
As I drew in my head
And was turning around
Down the chimney
St. Nicholas
Came with a bound
He was dressed
All in fur
From his head
To his foot
And his clothes
Were all tarnished
With ashes and soot
A bundle of toys
He had flung
On his back
And he looked
Like a peddler
Just opening
His pack
His eyes
How they twinkle
His dimples how merry
His cheeks
Were like roses
His nose like a cherry
His drawl little mouth
Was drawn up like a bow
And the beard of his chin
Was a white as the snow
The stump of his pipe
He held tight
In his teeth
And the smoke it
Encircled his head
Like a wreath
He had a broad face
And a round little belly
That shook when he laughed
Like a bowl full of jelly
He was chubby and plump
A right jolly old elf
I laughed when I saw him
In spite of myself
A wink of his eye
And a twist of his head
Soon gave me to know
I had nothing to dread
He spoke not a word
But went straight
To his work
And filled
All the stockings
Then turned
With a jerk
An laying a finger
Along side his nose
An giving a nod
Up the chimney
He rose
He sprang
To his sleigh
To his team
Gave a whistle
An away
They all flew
Like the down
Of a thistle
But I heard him exclaim
As he drove out of sight
Happy Christmas to all
And to all a good night
Hmmm
Merry Christmas from Barts-MS!