Wednesday, 1 August 2018

Q & A August



If you have a question unrelated to the thread this is the place for you

31 comments:

  1. Can you explain in simple medical terms why people with MS seem to be affected vy heat and why thusis gets worse as MS progresses. I have felt "wiped out" for much of this Summer.

    ReplyDelete
    Replies
    1. Hi Ian
      There's a number of posts on heat sensitivity and MS on the blog explaining what is happening. it's down to something called Uhthoff's phenomenon.
      Have a look here.
      http://multiple-sclerosis-research.blogspot.com/2013/04/heating-effect-on-nerve-conduction-in-ms.html

      Delete
    2. When you have demyelinated nerves (which increase as MS progresses), they are particularly sensitive to heat as this affects the nerve transmission, so as you heat up it affects how nerves transmit or not
      https://en.wikipedia.org/wiki/Uhthoff%27s_phenomenon

      It is a common feature in MS

      Delete
  2. Is this the mechanism of autoimmunity? The fatigue of immune system? Is EBV just a trojan horse?

    Surgical mesh implants, often used for hernia or gynecological repair, may be the reason so many patients report symptoms of an autoimmune disorder, according to a University of Alberta rheumatologist.

    "When a foreign body is put into the body, there is an instant activation of the immune system. It continues to fight the foreign body and eventually, over time, fatigues and becomes dysfunctional," he said.

    https://www.folio.ca/surgical-mesh-implants-may-cause-autoimmune-disorders

    ReplyDelete
  3. MS was around along time before surgical mesh was invented.

    ReplyDelete
    Replies
    1. Of course, the comment was about the mechanism, not mesh specifically. MS is not even mentioned at the research.
      But if this is a different way to get an autoimmune it needs a theory. The causes might differ but the diseases are the same and the mechanism is probably the same.

      Delete
  4. Multiple Sclerosis Development in Two Teens After HPV Vaccination

    https://www.neurologyadvisor.com/actrims-2018/pediatric-multiple-sclerosis-hpv-vaccine-gardasil/article/741559/?utm_source=newsletter&utm_medium=email&utm_campaign=na-update-20180804&cpn=&hmSubId=&hmEmail=VHU0u6r2Q_Y1&NID=%%NPI_NUM%%&dl=0

    Not clear...

    Obrigado

    ReplyDelete
  5. Hi does high bp cause MS progression. If so by breaching the BBB? Also a symptom of MS can be sleep deprivation. This in turn causes high bp. How can MS patients break this cycle to prevent progression?

    ReplyDelete
  6. Tongue-in-cheek suggestion: that all new doctors joining the NHS from other countries are required to read this Blog to provide them with an accurate image of what working here means culturally.

    Radio Times write up for new documentary 'The Foreign Doctors are Coming' on TV this evening. It focusses on the NHS shortfalls being addressed by recruiting from abroad. The review quotes one clinician: "Back home, says one ruefully, "we are gods, and patients just have to listen"

    ReplyDelete
  7. Nfl

    Serum neurofilament as a predictor of disease worsening and brain and spinal cord atrophy in multiple sclerosis

    https://academic.oup.com/brain/article-abstract/141/8/2382/5025690?redirectedFrom=fulltext

    Obrigado

    ReplyDelete
    Replies
    1. I guess we have been saying this for years. The correlations although highly significant need a programme to draw rather than being intuitive

      Delete
  8. Clinical trial to test the safety and potential of stem cells for the treatment of MS

    https://www.mssociety.org.uk/research/explore-our-research/research-we-fund/search-our-research-projects/clinical-trial-to-test-the-safety-and-potential-of-stem-cells-for-the-treatment-of-ms

    ReplyDelete
    Replies
    1. Years old...I think the conclusion was they were safe...but nothing convincing about efficacy.

      Delete
  9. How do mesenchymal stem cells from people with secondary progressive MS differ?

    https://www.mssociety.org.uk/research/explore-our-research/research-we-fund/search-our-research-projects/how-do-mesenchymal-stem-cells-differ

    ReplyDelete
    Replies
    1. This is all part of the same funding round...We terminated our grant early as we were never going to get any positive results...and no we were not working on aborted foetuses:-(

      Delete
  10. What is the publication frequency and timing of new posts? It use to be 1pm daily but doesn’t seem to folllow that anymore?!

    ReplyDelete
    Replies
    1. NDG has been posting at midnight on monday/tuesday.

      My posts have generally been 13.00 in the new regime but prefer to post in the morning not half-way through the day. 13.00 is apparently the time when most of the world is awake with regard to the internet.

      Prof G is not a number he is a free man:-). Your guess is as good as my guess. However during the holiday season we may be all over the World and not always in reach of the internet.

      Delete
  11. I just need some clarification. Previous blogs have mentioned the need for everyone, including those with progressive disease to be on a DMT in hopes of maintaining hand function. Does this include progressive patients that are in their 50’s with non enhancing MRI scans? Here in the USA, Ocrevus is being offered, but I wonder about the risks versus benefits.

    ReplyDelete
    Replies
    1. In US ocrevus is available for RRMS and PPMS, in Europe there is a more restricted use. The trials with ocrevus was done on people that were below 55 years and many of them were not enhancing when scanned. At post mortem most people with MS have active lesions

      Delete
    2. "At post mortem most people with MS have active lesions"

      Then why not showing up on MRI's..?

      Delete
  12. Can the G comment on this?

    https://www.ncbi.nlm.nih.gov/pubmed/30090637?dopt=Abstract

    ReplyDelete
    Replies
    1. I will comment. The title is misleading we are talking about the CRAB drugs, not current DMT. CRAB drugs are simply no efficacious enough

      Delete
    2. Are people aware that ProfG has been tweeting rather than Blogging, he answered your question 18h ago.

      Gavin Giovannoni @GavinGiovannoni

      Not sure if these investigators understand that SPMS is an artificial (Pharma invented) construct and that progressive MS is there from the beginning; it doesn't suddenly come on. When is the community going to accept that #MS_is_1_not_2_or_3_diseases? https://buff.ly/2vZP6jF

      Delete
  13. Why do HIV+ patients seem immune to MS?
    https://medicalxpress.com/news/2018-08-hiv-infection-antibody-block-cells.html

    It seems that IgG3 is expressed in chronic HIV infection by B cells as a way of dampening the immune response.

    ReplyDelete
  14. "Sequestration of T cells in bone marrow
    in the setting of glioblastoma and other
    intracranial tumors"

    https://www.nature.com/articles/s41591-018-0135-2

    What those this as to do with ms ?

    A bit... :)

    Gbm is a very nasty tumor ,it afects the immunne system ,like the ms

    drug fingolimod ,but ...20 times stronger

    "Concentrations of S1P are higher in the blood and lymph13, establishing
    a chemotactic gradient that directs T cell egress from lymphoid
    organs into the circulation. Disruptions to this gradient result in T cell
    trapping within lymphoid organs and pursuant T cell lymphopenia14.
    Such T cell sequestration is the intended mechanism of action for the
    drug fingolimod (FTY720), which is Food and Drug Administration–
    approved for multiple sclerosis.

    "The role of the S1P–S1P1 axis in immunology continues to
    emerge. S1P1 and S1P4 are highly expressed by T cells, with S1P1
    regulating T cell chemotactic responses11,24, but also impacting resident
    memory commitment25, Treg induction26, and IL-6-dependent
    pathways27,28. S1P1’s chemotactic function has made it a newer
    treatment target for the multiple sclerosis drug fingolimod27,29–31,
    whose aim is forced internalization of the S1P1 receptor on T cells
    to effect their sequestration in SLOs and decrease their transit to
    brain. Ironically, our data suggest that tumors of the intracranial
    compartment
    may usurp a previously unrecognized central nervous
    system capacity for eliciting this same phenomenon. Such a capacity
    may play a physiologic role limiting T cell access to the central
    nervous system and contribute to immune privilege

    "Subsets of patients with relapsing remitting multiple sclerosis
    experience a paradoxical exacerbation of multiple sclerosis and
    increase in brain-infiltrating Th17 CD4+ T cells when treated with
    fingolimod. Such patients frequently harbor a phosphorylationdefective
    S1P1, similar to our S1P1-KI mice, which likewise demonstrate
    an increase in TIL numbers27. We do not observe these
    to be Th17 polarized, however, which in the relapsing remitting
    multiple sclerosis patients may instead be a function of strong
    fingolimod agonism and resultant S1P1 signaling through the
    JAK–STAT3–IL17 pathway27,28. This agonism is not present in
    our therapy model (we did not administer fingolimod to S1P1-KI
    mice), suggesting that interventions targeting S1P1 internalization
    more specifically (and not signaling) may be effective at guiding
    increased numbers of functional T cells into intracranial tumors."

    Obrigado

    ReplyDelete
  15. MD, how about a quest post by Dr. Franz Schelling? It is very easy to contact him.

    ReplyDelete
  16. Cns autoantibodies are important?

    Guess not..


    Multiple sclerosis: Serum anti-CNS
    autoantibodies


    Abstract
    Background: It is uncertain whether there are autoantibodies detectable by indirect immunofluorescence
    in the serum of patients with multiple sclerosis (MS).
    Objective: To determine whether there are anti-central nervous system (CNS) autoantibodies detectable
    by indirect immunofluorescence in the serum of MS patients.
    Methods: Sera and in some cases cerebrospinal fluid from 106 patients with multiple sclerosis, 156
    patients with other neurological diseases, and 70 healthy control subjects were examined by indirect
    immunofluorescence using cryostat sections of rat cerebrum fixed by perfusion with paraformaldehyde.
    Results: Autoantibodies were detected that recognized more than 30 neuronal, glial, and mesodermal
    structures in 28 of 106 MS cases. Most were also detected in patients with other related and unrelated
    neurological diseases and several were also found in healthy controls. Novel anti-CNS autoantibodies
    recognizing particular sets of interneurons were detected in both normal controls and in subjects with
    CNS diseases.
    Interpretation: Serum anti-CNS autoantibodies of diverse specificities are common in MS patients.
    The same anti-CNS autoantibodies are not uncommon in patients with other neurological diseases. The
    findings provide no support for the proposition that myelin breakdown in MS is caused by exposure of
    intact myelin sheaths or oligodendrocytes to a pathogenic serum anti-myelin or anti-oligodendrocyte
    autoantibody.



    The study provides a catalogue of anti-CNS antibodies
    that are sometimes present in the serum of
    patients with MS. It is likely that many of the antibodies
    are previously undescribed natural autoantibodies
    of the sort known to be highly seropositive in
    health and disease. The study says nothing of the
    specificity of MS CSF IgG or serum antibodies that
    recognize determinants that are expressed or accessible
    only in MS tissue

    http://journals.sagepub.com/doi/abs/10.1177/1352458518774880?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&

    Obrigado

    ReplyDelete
    Replies
    1. MD, how about a quest post by Dr. Franz Schelling? It is very easy to contact him.

      I would don't mind if Beki wants to contact him for a guest post, maybe he can put his book into to bite size bits. To me it was a cure for insomnia, as it was not an easy read :-). maybe I wil be blogging about a blog post.

      We would like a bio and conflict of interests statement, VV why not write one. We can show a picture of a closet, so you don't need to identify yourself.

      Delete
    2. "It is uncertain whether there are autoantibodies detectable by indirect immunofluorescence in the serum of patients with multiple sclerosis (MS)".

      There are a list of papers as long as your arm documenting autoantibodies in MS. The central question is whether they are of primary significance or whether they are secondary to damage that occurs, etc.

      However the comment "It is uncertain" means we are talking mushroom food and don't want to admit that there is tons of work showning what we are about to repeat for the Nth time and that it has been done before.

      However, we want to pull the wool of the eyes of the lazy reviewer who is going to let us get away with this statement. This is because if they called us on in they would realise we are no doing anything new!!.

      Yes you can call me cynical. However this terminology is part of "bad science" that surrounds us every day. I would say "Please be honest and frame your work in the context of what others have found." Replication of important results is important.

      Delete
    3. "bad science"

      Actually i was seeing Dr Prineas profile on Research Gate

      https://www.researchgate.net/profile/John_Prineas

      And this is his latest paper

      Not sure if he is known for doing "bad science"

      Obrigado

      Delete

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