Tuesday, 7 July 2015

MS. It's all in a Name

#MSresearch visit http://narcoms.org/ to have your say on have to you want to be described. Please retweet

We recently asked how they would prefer to be referred to in academic outputs and in the social media.

We know that people don't like to be labelled, but this does indeed happen and we appreciate that you are not all happy with the choices but they are: Client; MSer; Person with MS; Patient; and Sufferer

The MS Register did a fantastic job and please consider signing up to this registry, but this was only open to people within the UK.

However, you said you would like to have an input, but you are not from the UK. 

We said we would write to NARCOMS in the USA, as they too have a Registry and they have also agreed to run the survey for two weeks from 6th July-13th July.

Please visit the NARCOMS site (CLICK HERE) and make a contribution, and if new why not sign up to NARCOMS.

You will see a request to complete a 2-question online survey about preferred descriptors for someone with MS.

Thanking you for your input.

ClinicSpeak: progressive MS and upper limb function

Should we target arm, swallowing and speech in progressive MS? #MSBlog #MSResearch #ClinicSpeak

"We did our 4th MS Roadshow last Saturday at the Chilterns MS Centre. The Roadshows are meetings we do outside of our annual MS Research Day. The purpose of the Roadshows are to take our research into the community. Our focus this year has been on progressive MS trials, both disease-modifying and symptomatic. The aim is to present our research and what is generally happening in the field of MS research. We actively encourage MSers to participate, or at least put themselves forward, for clinical trials. Without volunteers for clinical trials we will never move the field forward."

"At the end of the meeting one of the MSers who was in a wheelchair stated that after our presentations she felt, for the first time, that the research community was taking progressive MS seriously and that she felt confident that a breakthrough in progressive MS was just around the corner. Our presentations were the most positive she had heard in relation to progressive MS; she was convinced by our arguments that we could really do something for progressive MSers. She was in a wheelchair. She was particularly impressed that I made the statement: 'because you are in a wheelchair why shouldn't we try and delay further disease progression and protect your upper limb function and your ability to swallow and speak?'."

"This sentence subsequently bounced around inside my head all weekend. Yes, why shouldn't we try and preserve upper limb and bulbar function in wheelchair-bound MSers? If our length-dependent axonopathy hypothesis is correct and the same mechanisms are driving upper and lower limb progression why shouldn't we enrol MSers in wheelchairs and include them in trials with the aim of preserving upper limb and bulbar function? It has become very clear to me based on the comments in relation to my destigmatizing the wheelchair post that MSers need to have some hope beyond EDSS 6.5. If we exclude wheelchair users from all progressive MS trials we destroy any hope they may have of preserving their independence in the future. As a community are we prepared to simply condemn wheelchair users to the face the ravages of the disease without any hope? I therefore propose exploring whether or not we can power a trial to look at upper limb function as a primary outcome for progressive MS trials. May be we can design the trial so that we can assess upper limb function using a web-based keyboard task that MSers can complete at home? This would mean they could do most of the assessments at home and avoid, or at least reduce, tiring journeys to the trial centre."

"If you have a moment could you please complete the following survey on this issue?"

Some stem cells may not cause remeylination

Salinas Tejedor L, Berner G, Jacobsen K, Gudi V, Jungwirth N, Hansmann F, Gingele S, Prajeeth CK, Baumgärtner W, Hoffmann A, Skripuletz T, Stangel M. Mesenchymal stem cells do not exert direct beneficial effects on CNS remyelination in the absence of the peripheral immune system. Brain Behav Immun. 2015 Jun. pii: S0889-1591(15)00233-0

Remyelination is the natural repair mechanism in demyelinating disorders such as multiple sclerosis (MS) and it was proposed that it might protect from axonal loss. For unknown reasons, remyelination is often incomplete or fails in MS lesions and therapeutic treatments to enhance remyelination are not available. Recently, the transplantation of exogenous mesenchymal stem cells (MSC) has emerged as a promising tool to enhance repair processes. This included the animal model experimental autoimmune encephalomyelitis (EAE), a commonly used model for the autoimmune mechanisms of MS. However, in EAE it is not clear if the beneficial effect of MSC derives from a direct influence on brain resident cells or if this is an indirect phenomenon via modulation of the peripheral immune system. The aim of this study was to determine potential regenerative functions of MSC in the toxic cuprizone model of demyelination that allows studying direct effects on de- and remyelination without the influence of the peripheral immune system. MSC from three different species (human, murine, canine) were transplanted either intraventricularly into the cerebrospinal fluid or directly into the lesion of the corpus callosum at two time points: at the onset of oligodendrocyte progenitor cell (OPC) proliferation or the peak of OPC proliferation during cuprizone induced demyelination. Our results show that MSC did not exert any regenerative effects after cuprizone induced demyelination and oligodendrocyte loss. During remyelination, MSC did not influence the dynamics of OPC proliferation and myelin formation. In conclusion, MSC did not exert direct regenerative functions in a mouse model where peripheral immune cells and especially T lymphocytes do not play a role. We thus suggest that the peripheral immune system is required for MSC to exert their effects and this is independent from a direct influence of the central nervous system.
There are many types of stem cells, but the hope of MSers is that they will cause repair. In a recent debate on stem cells at the MS Society it was argued that (a) Stem cells have only a modest effect by causing immune modulation (b) Few cells can get into the CNS an (c) They don't cause much remyelination. In this study they take one type of stem cell and they inject them into the brain of mice with mice with chemical-induce demyelination, which is used to study remyelination drugs and the stem cells do nothing towards repair.

In response to your desires these approaches have already been tried in MS...so are they going to work? Maybe an Maybe not. However, the expectation should not be too unrealistically high.
If they do, things can be better an if they don't...do not blame the animals.

Listeria with Alemtuzumab - 2 cases reported

Int J Mol Sci. 2015 Jun 29;16(7):14669-14676.

Listeria Meningitis Complicating Alemtuzumab Treatment in Multiple Sclerosis-Report of Two Cases.

Rau D, Lang M, Harth A, Naumann M, Weber F, Tumani H, Bayas A.


Alemtuzumab, a humanized monoclonal antibody targeting the surface molecule CD52, leads to a rapid depletion of immune cells in the innate and adaptive immune system. In phase 2 and 3 trials in multiple sclerosis (MS), infections have been reported more frequently in alemtuzumab than in interferon beta treated patients. Here we report two patients treated with alemtuzumab for MS developing Listeria meningitis few days after the first infusion cycle. Both patients recovered completely after prompt diagnosis and adequate treatment. Physicians and patients should be aware of this serious, but treatable complication.

Listeria monocytogenes is rod-shaped bacterium and is mainly acquired from eating contaminated foods. The CNS infection in particular is very serious and has a high fatality rate if not picked up early but also has a 30% mortality rate even if appropriately treated. It is rare - 0.1 to 10 cases/million, and as a neurologist I've only seen two cases! It mainly affects the very young and the very old, but also the immunosuppressed. And this is where Alemtuzumab comes into play.

Here the authors describe two cases of Listeria meningitis which occurred after the first infusions, and the Alemtuzumab will be presumed causative of the infections.  Previously a single case of Listeria meningitis has been reported in the CAMMS study, bringing the total up to 3 cases.

Alemtuzumab depletes both the adaptive (T cells) immune system and the dendritic cells which communicate with the innate immune system, thereby facilitating the propagation of the infection once started. There are available antibiotic therapies and the first line commonly used is Ampicillin, belonging to the Penicillin family. As a precautionary measure, avoidance of potential contaminated sources around the time of infusion and during the period of low WBC counts (i.e. 6 months after the infusion) may be another strategy.