Wednesday, 21 February 2018

Our Prime Minister has the decency to send her apologies

We are hosting our #ThinkHand awareness event tomorrow night. We were hoping to get Theresa May to attend and endorse the event. At least she responded. JK Rowling didn't even acknowledge our invitation. Very poor form? 




Tuesday, 20 February 2018

CSF neurofilament light chain and OCB predict conversion to MS in RIS

CSF neurofilaments are ready for prime time. Do you agree? Wouldn't you as someone with MS not want to know what their CSF NFL levels were? 


Inflammation and nerve damage occur before you even know you have MS

I didn't realise that NDG had done this but here are my thoughts...

Monday, 19 February 2018

Here comes #ChariotMS. Or does it?

Is the #ChariotMS study worth funding? Is upper limb function worth saving in people with more advanced MS?



The objectives of our #ThinkHand awareness event, which we are hosting this Thursday night, is to celebrate hand function in people with MS and to promote #ChariotMS to the wider community.


Risk of haemolytic anaemia after alemtuzumab

Alemtuzumab use has been associated with the development of secondary autoimmunities.

Antibodies to Red blood cells can be one of these


Sunday, 18 February 2018

Changing Documents. Will it impact on changing practice?

All senior scientists who work in the University sector in the UK are being monitored for their output to determine whether they are of International standing and whether their work has any Impact.

Check this out to explain (CLICK. Performance culture is ruining scientific research), it's quite a sorry state of affairs.

What is Impact?


Does the work change clinical practice? or perhaps science practice or policy? 

Sometimes we have to remind you of the stuff we have done.

Friday, 16 February 2018

Thursday, 15 February 2018

Crowd-funding: Listeriosis Prevention Pack

We, Barts-MS, and the NHS needs your help to try and prevent Listeriosis after alemtuzumab treatment. We are raising money to produce a Listeriosis Prevention Pack. 


Barts-MS Listeria Prevention Pack Prototype

Drugs doing more than one thing, it's not always good

Morrow SA, Rosehart H, Sener A, Welk B. Anti-cholinergic medications for bladder dysfunction worsen cognition in persons with multiple sclerosis. J Neurol Sci. 2018 385:39-44.

Bladder dysfunction is common in persons with MS (PwMS), often due to muscle overactivity. Anti-cholinergic medications are considered the first line treatment for bladder dysfunction and are known to worsen cognition in healthy older adults and in persons with dementia. Yet, it is not known if these medications have the same effect on PwMS. Thus, the Objective of this prospective matched-cohort study was to determine if anti-cholinergic medications affect objective measures of cognition in PwMS. 

We recruited PwMS starting either oxybutynin or tolterodine (cases). Cases and controls were tested with the Brief International Cognitive Assessment for MS (BiCAMS) battery prior to starting anti-cholinergic medications and 12weeks later.
  The primary outcome was change on the Symbol Digit Modalities Test (SDMT) between groups; secondary outcomes were changes on the other BiCAMS measures. Analysis to assess the significance of between group differences was performed at 12weeks. Forty eight PwMS starting anti-cholinergic medications and 21 matched PwMS controls were recruited. There was a significant difference (p<0.001) in the change on the cognitive measures over 12 weeks between groups. The controls demonstrated improvement, consistent with practice effect, while the cases remained unchanged. This study demonstrates that anticholinergic medications may have a negative effect on cognition in PwMS.


Anti-cholinergic drugs block acetyl (ace-eee-tile) choline activity. Aceyl choline is a neuro-transmitter. Acetylcholine functions in both the central nervous system (CNS) and the peripheral nervous system (PNS). In the CNS, cholinergic projections from the basal forebrain to the cerebral cortex and hippocampus support the cognitive functions of those target areas. In the PNS, acetylcholine activates muscles and is a major neurotransmitter in the autonomic nervous system.The autonomic nervous system is a control system that acts largely unconsciously and regulates bodily functions such as the heart rate, digestion, respiratory rate, pupillary response, urination, and sexual arousalThere are two main classes of acetylcholine receptor, nicotinic and muscarinic. Block acetylcholine and you can get dry mouth constipation  flush skin.


You can get leakage from a bladder because the muscle is contracting too much, anti-cholingrerics can block this. If you can't go, cholinergic agonists can contract the bladder to empty it.  However in addition to blocking over active bladder, it can block nerve action involved in thought processes. 


Why is this important? Because it shows you that the body can use the same system to control more than one function. They could be have universal good things but they can be opposing one good and one bad. Many of the the agents that promote remyelination have alternative functions and don't be surprised is some of those found to be useful in myelination may have unwanted effects. But do we need to take remyelinating drugs forever or just for a short time so that myelination starts?


Wednesday, 14 February 2018

Education: What is a nerve impulse?

What is a nerve impulse? How does a nerve axon generate it and allow signalling using impulses from one place to another?

The impulse may be thought of as a message or wave.  A ‘message’, for example on a telegraph, or a ‘wave’ in the sea initiates at one point and ends up elsewhere. The message needs the medium: the wave may have travelled great distances, but it cannot exist without the sea, whereas the sea itself has not moved. Likewise, the anatomical connectivity of an axon does not change as impulses are transmitted. A telegraph message requires an unbroken line. If the telegraph line somewhere between Laramie and Denver in the old West is broken, then the message does not get through and the bandits might escape justice. There is a similarity here with the nerve impulse and the axon. The axon has to make the impulse and provide a conduit for its conduction.



Monday, 12 February 2018

Guest post: Why hasn't the reality of hidden disabilities caught on yet?

Twice in the past couple of months I’ve been reduced to tears because I’ve seen media stories about people with hidden disabilities being treated appallingly by people in customer-facing positions who should be the ones leading the way when it comes to helping those who might need that extra bit of help. In both the stories, the two women were told they didn’t “look disabled.” 

As someone with MS who most of the time looks perfectly healthy, it’s something that really resonates. I hope that you will share this post far and wide, if nothing else so that every individual who reads this will remember that old saying “don’t judge a book by its cover.”



Sunday, 11 February 2018

My trip to Lucerne and the Charcot Project

A few weeks ago I was invited to give a lecture at the annual Swiss MS Society meeting on 'The Charcot Project' and the rationale behind using anti-viral drugs to treat MS.



As promised my slides from the meeting; they should be self-explanatory:


Saturday, 10 February 2018

What is your risk of developing PML on fingolimod?

The following update on PML risk on fingolimod was released to us by Novartis. 


Will this new data lead to a change in practice? 

Friday, 9 February 2018

Guest post: The argument for legalising cannabis for medicinal use

Note: This is a post which talks about the effects of PPMS in a way that some readers may find upsetting.

We are a regular family who has been virtually decimated by MS.

Education: Cannabis

If you are interested in the biology of cannabis you can flick through these slides


Thursday, 8 February 2018

Neural Stem cells to the Rescue?. Phase I trial results

VK Harris et al. Phase I Trial of Intrathecal Mesenchymal Stem Cell-derived Neural Progenitors in Progressive Multiple Sclerosis
EBiomedicine DOI: https://doi.org/10.1016/j.ebiom.2018.02.002

Highlights

Multiple sclerosis is one of the leading causes of disability in young adults. Our study is the first evidence suggesting that a cell-based therapeutic approach is capable of reversing disability in multiple sclerosis. Results of our study add to existing evidence demonstrating the safety and tolerability of intrathecal administration of autologous mesenchymal stem cell-derived neural progenitors. The study was associated with repeated administrations of cells freshly harvested from culture, as opposed to cryopreserved cells thawed at the bedside, which may have contributed to the observed efficacy of the treatment. The continued development of this therapeutic approach will likely have implications for treating other neurological diseases.

Background
Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system and is one of the leading causes of disability in young adults. Cell therapy is emerging as a therapeutic strategy to promote repair and regeneration in patients with disability associated with progressive MS.
Methods
We conducted a phase I open-label clinical trial investigating the safety and tolerability of autologous bone marrow mesenchymal stem cell-derived neural progenitor (MSC-NP) treatment in 20 patients with progressive MS. MSC-NPs were administered intrathecally (IT) in three separate doses of up to 1 × 107 cells per dose, spaced three months apart. The primary endpoint was to assess safety and tolerability of the treatment. Expanded disability status scale (EDSS), timed 25-foot walk (T25FW), muscle strength, and urodynamic testing were used to evaluate treatment response. This trial is registered with ClinicalTrials.gov, number NCT01933802.
Findings
IT MSC-NP treatment was safe and well tolerated. The 20 enrolled subjects completed all 60 planned treatments without serious adverse effects. Minor adverse events included transient fever and mild headaches usually resolving in <24 h. Post-treatment disability score analysis demonstrated improved median EDSS suggesting possible efficacy. Positive trends were more frequently observed in the subset of SPMS patients and in ambulatory subjects (EDSS ≤ 6.5). In addition, 70% and 50% of the subjects demonstrated improved muscle strength and bladder function, respectively, following IT MSC-NP treatment.
Interpretation
The possible reversal of disability that was observed in a subset of patients warrants a larger phase II placebo-controlled study to establish efficacy of IT MSC-NP treatment in patients with MS.
Here are exerts from the paper which is open acess
"The clinical feasibility of IT MSC-NP treatment in MS was initially investigated in six patients with advanced MS treated with two to five injections of escalating doses of autologous MSC-NPs. PwMS were followed an average of 7.4 years after initial injection. There were no serious adverse events or safety concerns noted, and the treatments were well-tolerated. Four of the six patients showed a measurable clinical improvement following MSC-NP treatment". 
In this current study "eligible patients had clinically definite SPMS or PPMS with significant disability (EDSS ≥ 3.0) that was not acquired within the 12 months prior to enrollment. The inclusion of patients with a relatively stable disease state was designed to allow better discernment between natural disease progression and treatment-related events. To minimize additional variables, patients who were already receiving disease-modifying therapies (DMT) upon entering the study continued as a concomitant treatment through the course of the study". 
"There were no serious adverse events or hospitalizations associated with IT MSC-NP treatment" 
"The safety data was further supported by a lack of any change in brain MRI scans during the study. Specifically, no new T2 lesions or changes in disease burden were observed". 
"The study design was not blinded, and there were no placebo controls". 
Therefore, be warned the power of the placebo should not be under-estimated. The placebo effect where you get better after taking nothing can be immense and has sent many good ideas to their graves.
The primary post-treatment clinical assessments were conducted at three and six months following the third treatment and compared to baseline (pre-treatment) in order to determine trends in efficacy. Of the 20 study subjects, 15 (or 75%) demonstrated neurological improvement associated with IT MSC-NP treatment. 
Improvements were documented in the following areas: EDSS, MRC muscle strength scale, timed 25-ft walk (T25FW), and/or bladder function.Of the remaining subjects, two showed disease worsening despite the treatment, and three subjects showed no change.
The predefined endpoint was adverse effects but secondary endpoints were evidence of efficacy allowing the centre to pick and choose and so data hack to spin the best story. 
                                               EDSS

So as you can see 4 people showed qute a bit of improvement and there were reports of improvement for other outcomes notably the lower limbs and bladder rather than upper limbs and cognition.

So first things first you can see it is not a miracle cure and therefore we need to view these results positively, but also objectively. 

The myth being spun is that stem cells will turn back the clock and for most people here, this is not the case, so we need to understand the reality of these studies. It is a start

This study injected live growing cells and so they are producing a group of "potential goodies" that may be growth factors.

Wednesday, 7 February 2018

Worldwide occurance of JC virus

Are you JCV positive? What are your chances of being positive? 


Tuesday, 6 February 2018

Education: About EBV Infection

A post for people who need to know more about EBV.


That damned, elusive EBV

Will this study get the field behind the EBV hypothesis once and for all? Or will it be another bun fight?


Sunday, 4 February 2018

Walking speed improvements

Walking improvement can be achieved with fampridine, which is a slow release formulation of an old drug called 4-aminopyridine. 

Here, we have a slow release of a different old drug (amantadine) to also improve walking speeds.

Questions and answers Feb 2018

If you have a question this is the place for you


Saturday, 3 February 2018

How easy is it to design an algorithm to sequence DMTs?

Last week DrK and I joined an esteemed panel of academic neurologists (all male, unfortunately*) to discuss issues around the sequencing of DMTs.



*We need more women on platforms such this and other MS-related committees. The gender divide is very large in the field of MS. It is very embarrassing to me as a father and husband; my daughters and my wife are card-carrying feminists and every bit as capable as their male peers.  

The following is my presentation that many of you requested. You can download it from SlideShare.

Friday, 2 February 2018

Request a blog post from Barts-MS

Reader, sometimes we tell you want we want to tell you. Sometimes we tell you what we're working on or what we've read about. Now, we'd like YOU to tell us what you want to read.

Comment below with a burning question, or a topic you wish to be covered, or an aspect of MS that you'd like us to explain. We'll find someone in the team to write that post for you over the coming weeks.

What do you want to know about MS?

Thursday, 1 February 2018

Does your age predict how well you respond to DMTs?

Did you know that if you have MS and are older than 53 years of age you are unlikely to respond to DMTs?