Tuesday, 22 May 2018

The neurologists tool kit - Stornoway talk

Photograph: (left to right) myself, Klaus Schmierer, Gareth Pryce, Gavin Giovannoni, David Baker, Stewart Webb, Sarah-Jane Martin, (below) Isle of Lewis.

I've been asked to put in writing the second of my Stornoway (on the Isle of Lewis) talks. The title is 'the neurologists tool kit' and provides an overview of your visit to your neurologist in plain speak. In many ways what is written below are my thoughts on the topic, and is by no means the sum of all practical wisdom!!!

Look back at your first clinical encounter, I would say a vast majority of you would have left without a clear understanding of what just happened - am I right? That's because often the objectives from the two sides are not always the same. 

In the UK, on average a person with MS waits 3-4 months to see an MS neurologist. Through necessity the main source of information becomes Dr Google; I'm not saying this is wrong, but simply a fact. Everything beyond this is simply a succession of moments in time, layered in legitimate facts and misinformation. Conversely, your MSologist at your first visit is viewing you in the following terms: is the diagnosis correct, do I need to do more investigations, what is the prognosis, are they eligible for treatment or suitable for clinical trials, how do I manage expectations - and the list goes on. 

If this sounds unfamiliar, familiarizing yourself with the two sides will go a long way to improving your experience. 

My goal with those that I see is to educate, educate, educate...and ultimately empower each person to be able to direct their own care. It is often an exacerbating experience to start off with, but one that is more fulfilling in the future.

So what is in an MS neurologists tool kit?

1) Clinical skills

This by far is the most important thing we have in our tool kit as clinicians. Our training is often protracted, and full of additional courses and degrees to allow us to accurately diagnose and manage neurological conditions. To the more senior of us the diagnostic process is almost pattern recognition and begins when you walk into the consulting room. 

A person's history is very important in the diagnostic process and informs us of the chronology of events, whether it's progressive, and the rate of progression. While the clinical examination informs us of the pathways involved, which allows us to determine where the problem is. Any investigations that follow are based on the information garnered from the two. 

This is why a computer may never replace what we do to good effect; the best diagnostician is our own brain.

Figure: Myotomes; muscle innervation by nerve roots. One aspect of what is involved in a neurological exam.

2) Investigations: MRI & lumbar puncture

An MRI head and spine study provides the descriptive information about the area of brain or spinal cord involved. The underlying causes of these lesions can be more than one, but the pattern of distribution may make one more likely rather than another, i.e. inflammatory lesions vs. stroke/small vessel disease. Sequential MRIs may also allow us to prognosticate; wherein the accrual of new lesions is indicative of active disease or treatment failure. Neurologists may also comment on brain volume loss at the outset, and will almost certainly direct you to the more highly active therapies. 

A lumbar puncture, on the other hand, provides the biological reason behind the disease. The presence of oligoclonal bands/antibody production in your spinal fluid is almost diagnostic of MS. Not surprisingly, the presence of bands in your spinal fluid also increases your risk of continued disease activity and clinical progression. Recently, we introduced the testing of neurofilament proteins that reflect the degree of breakdown of neurons in your brain and spinal cord. If you have high levels of neurofilaments in your spinal fluid, then you have more of a chance of disease progression and accruing disability faster than a person with normal levels. If you'd like this tested by your doctor, here is the link: http://multiple-sclerosis-research.blogspot.com/2018/02/barts-health-csf-neurofilament-light.html

Photograph: We received this years Innovation Award 2018 for the introduction of neurofilament testing at Barts Health (left to right: Francesca Ammoscato, myself and David Holden; not in the picture Lucia Bianchi)

3) Clinical trials: EDSS, 9-HPT

Always inquire about clinical trials. Clinical trials allow you to access newer treatments 6 to 10y before they are available for clinical use. Moreover, participation in the trials may mean that after trial completion you have access to the treatment in question on a compassionate basis, whilst the drug is in the process acquiring license for prescribing. 

The visits can be sometimes long-winded and often involve assessments of disability (EDSS, timed 24 foot walk and 9-hole peg test for the upper limb function), imaging and in some cases a lumbar puncture. 

Trials are also an important educational resource about MS and provide an insight into current MS research.

Figure: The EDSS score

4) Future: self-monitoring

Online applications and wearables empower us to track our own health. It is almost impossible to clearly remember your last relapse or how your overall health fared this year compared to the last. The hope is that as we use the data from these devices, the consultations become more tangible and more targeted (i.e. personalized), so that the hospital visit is more informative. 

If you haven't already done so, check out the Apps available for the iphone/android devices: Microsoft health vault, Sym Trac, MSAA (My MS Manager), and disability calculator (provided by Rebif manufacturers).

Hope you have found this post useful, and good luck!

Monday, 21 May 2018

What is HSCT?

I seem to be spending a lot more clinic time explaining to my patients about HSCT. What is happening and why?

Sunday, 20 May 2018

Saturday, 19 May 2018

Have your say on the big NHS England MS debate?

You may be aware that NHS England has just closed the public consultation period for the new NHS England Treatment MS DMT Algorithm. The aim of the algorithm is part of a troika, along with Blueteq and MDTs (multidisciplinary team meetings) to reduce the variation in prescribing of DMTs across England. The question is will this algorithm achieve its aim?

The following is the debate we had on this topic last week at the ABN in Birmingham. Please have your say; watch the debate and vote.

2018 List of Best MS Blogs

We have made the Healthline 2018 list of "Best MS Blogs". We have changed the blog in the last 6 months; fewer posts, more guests and less science. Do you think this has improved the blog? We would welcome suggestions going forward. For example, we are thinking of migrating the blog from Blogger onto a better and more responsive platform. 

Friday, 18 May 2018

Your brain stiffens

Rheology is the study of the flow of matter

An interesting brain fact if you are interested

Thursday, 17 May 2018

Depression to reduce MS

Sacramento PM, Monteiro C, Dias ASO, Kasahara TM, Ferreira TB, Hygino J, Wing AC, Andrade RM, Rueda F, Sales MC, Vasconcelos CC, Bento CAM. Serotonin decreases the production of Th1/Th17 cytokines and elevates the frequency of regulatory CD4+ T cell subsets in multiple sclerosis patients. Eur J Immunol. 2018 May 2. doi: 10.1002/eji.201847525. [Epub ahead of print

Excessive levels of pro-inflammatory cytokines in the central nervous system (CNS) are associated with reduced serotonin (5-HT) synthesis, a neurotransmitter with diverse immune effects. In this study, we evaluated the ability of exogenous 5-HT to modulate the T-cell behaviour of patients with multiple sclerosis (MS), a demyelinating autoimmune disease mediated by Th1 and Th17 cytokines. Here, 5-HT attenuated, in vitro, T-cell proliferation and Th1 and Th17 cytokines production in cell cultures from MS patients. Additionally, 5-HT reduced IFN-γ and IL-17 release by CD8+ T-cells. By contrast, 5-HT increased IL-10 production by CD4+ T-cells from MS patients. A more accurate analysis of these IL-10-secreting CD4+ T-cells revealed that 5-HT favours the expansion of FoxP3+ CD39+ regulatory T cells (Tregs) and type 1 regulatory T cells. Notably, this neurotransmitter also elevated the frequency of Treg17 cells, a novel regulatory T-cell subset. The effect of 5-HT in up-regulating CD39+ Treg and Treg17 cells was inversely correlated with the number of active brain lesions. Finally, in addition to directly reducing cytokine production by purified Th1 and Th17 cells, 5-HT enhanced in vitro Treg function. In summary, our data suggest that serotonin may play a protective role in the pathogenesis of MS.

In this study they found that serotonin (5-HT), which is the "happy" neurotransmitter that stimulates brain areas, may help animals with EAE. If this is true they we should have the answer quite soon as MS SMART has been using fluoxitine, which is also known as a prozac and is an SSRI (selective serotonin reuptake inhibitor) meaning that it induces more serotonin in the system....leading to less depression, but does it mean less Th1/Th17 and less MS.

"The objective of the Fluoxetine for Progressive MS study in Belgium and the Netherlands was to see if fluoxetine could slow the progression of MS. The trial (ECTRIM2016) covered both people with primary progressive MS and secondary progressive MS. Participants were divided into two groups. The 69 people in the first group received a 40 mg-per-day dose of fluoxetine (Prozac) for 108 weeks. The 68 people in the second group received a placebo.
Researchers found no significant difference in disease progression between the two groups".

So is the idea a bad one or was it that the trial design meant that a sensible answer could not be found.

Wednesday, 16 May 2018

The Cost of MS is more than just your Health

Last week, we said that Neuros could supplement their income from pharma-related activities.

Next there was a flurry of emails, asking for disclosure of how much, if anything, I get from MS pharma and elsewhere.

Having skirted round the issue, as I am not discussing my personal life, the question is what happens to your income?

Whilst on an individual level, I think it is none of my business, but as I am sure you know, MS does not just cost you your health...but also your wealth.

Even more reason to make sure you deal with MS as best you can as early as you can.

Tuesday, 15 May 2018

The importance of weight in MS

Acta Neurol Scand. 2018 May 11. doi: 10.1111/ane.12959. [Epub ahead of print]

Body mass index and cardiorespiratory fitness in persons with multiple sclerosis.

Monday, 14 May 2018

Guest Post- Animal Studies Enough Already

In response to Yesterday's Post

My photo
Enough with the mouse studies, already! In the 15 years since my diagnosis, I've read countless research reports involving EAE and other mouse models of multiple sclerosis. Only an infinitesimal amount of these reports have ever proven to have any real relevance to the human MS population.

The simple fact is this: mice don't get ms. You can inject them with myelin or other toxins and achieve something that kind of sort of looks like MS, but it's not ms. Then, it seems as if staring intently at the mice long enough or breathing on them shows some kind of benefit. Honestly, it's almost come to that level of ridiculousness.

We must come up with better models of the disease to work on. The amount of time and money wasted on mouse studies is – given the the enormity of the impact of MS on those humans it attacks – obscene.

Really, it's time to rethink our entire approach to MS research. Thus far the best we've come up with are treatments that profoundly suppress parts of the intricate human immune system, the long-term effects of which are a complete unknown. And these treatments do absolutely nothing towards effecting a cure.

Given modern laboratory techniques, the rapid advances in computational power, the emergence of AI, and the vast body of knowledge accumulated by ms researchers and clinicians, one would think a coordinated, concerted effort to finally identify the cause or causes of the disease might finally bear fruit. Time spent fixated on mice with induced conditions that sort of resemble MS is, at this point, time wasted. And those of us forced to watch ourselves disappear by inches don't have that time to waste.

Patients should be rising up against the status quo, but unfortunately most are too busy just trying to get through the day with some modicum of functionality and dignity left intact. MS has gone from medical backwater to one of the most profitable areas of medical practice in the last two decades. It's high time to cure the damn thing and send it back from whence it came. We now have the technology and basic understandings of the mechanisms to get this done, given the will. Coming up with an effective anti-EBV treatment would be a great first step…"
This was a comment made yesterday and is an opinion I am sure many people hold. Likewise, many neuros think the same.  However, basic science is the basis of where treatments come from. 
I was at a recent meeting about finding treatments, which may involve a bit of screening in animals and a very eminent scientist said (Paraphrased) I'm not going to do that as I'm not interested. All I am interested in doing is looking at mechanisms of biology. 

However they are very happy to take money from disease-related charities.

What you do think?

The science publishing system has created a "mechanism is all mentaility" and disease can simply be a vehicle to get research support. 

However times are changing and it is increasingly difficult to get funding for animal studies. However, without knowledge, we will continue to shoot in the dark.