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.
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
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.
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.
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?
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"
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:-(
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.
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.
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
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
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."
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
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.
"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.
Not adequatedly framing your work in the context of what is known from the work of others by deliberately ignoring it it with the view of deceipt to make your work look better, is in my opinion bad science and I dont care who it is.
Indeed sadly it is often the demi gods of science that do this to up the importance of their work. A sad fact of life.
PS John Prineas has a excellent reputation, but I have heard people question the finding about the early lesion.
Striving for Ideal Cardiovascular and Brain Health It Is Never Too Early or Too Late
Better heart better brain
Several lines of evidence suggest that improved control of cardiovascular risk factors is a substantial contributor to declines in dementia.
The 2 reports in this issue of JAMA draw on the influential Life’s Simple 7 cardiovascular health metric from the American Heart
Association (AHA), which is being used to measure and pro- mote individual- and population-level improvements in car- diovascular health. 11 With contributions from 4 modifiable health behaviors (nonsmoking, healthy diet, physical activ- ity, and body mass index) and 3 modifiable biological health factors (low blood pressure, low cholesterol, and low fasting glucose), the score indicates the degree to which an individu- al’s alterable health factors are in accord with ideal cardiovas- cular health and optimal cerebrovascular and brain health. 1
Thanks for the post. The paper was recently published in Lancet by the team from the Cleveland Clinic. This subtype of MS is independent of white matter degradation and involves neuronal cell death as the predominant pathology.
Maybe MS is still one disease but instead of demyelination neuronal cell death is the initial pathology. It seems that the individual's immune response dictates the subtype of MS. Is there a robust adaptive immune response that is responsive to the B and T cell DMDs? Or does neurodegeneration occur independently of lymphocytes and lead to progressive forms of MS not responsive to DMDs?
Also why not comment on breaking news as the article? Let patients now your views whether take or real breakthrough? Can be weekly if need be. Surely as researchers u will be eager to give your opinion. Instead of patients bringing the news to barts.
Patients bringing news to us…why not pwmS have been doing this for years.
Many years ago NMO was called Devics MS, there is Marburg MS, Balos MS etc etc
I am away and have not seen the article. Neurodegeneration without evidence of demyelination. I have seen this in EAE loads of times. In peripheral nervous disease you get bands of bungner where the transected axons repsprout down the old myelin sheath.
One swallow does not make a summer and if I make a section and find neurodegeneration in one part of the brain could it not be that the damage was some distance away and you had death of a nerve somewhere else.
"but here they find cortical neuronal loss in the absence of white matter involvement."
Not sure. But is maybe the axon more sensitive/vulnerable to a hostile environment than the myelin is..? In the oven does the hot dog cook first or the bun..? Someone test this out please.
If after two courses of lemtrada there is still worsening of the disease why is there no pressure being put on nice to approve further treatments? What is happening to those patients? Are they simply having no further treatment for the disease or are they having other already existing treatments or are they waiting for ocrelizumab? Based on the inability to access more treatments than the two initial treatments are neurologists not prescribing lemtrada?
I hope I'm right in saying that it is possible to have a third round of Alemtuzumab on the NHS.
Recall, I think, ProfG posting as much and my neuro told me, in June, that she didn't have it there in writing to prove it to me, but to all intends and purposes it's a done deal, if I should need another treatment.
Case Study Suggests Need for New Treatment Strategy When Switching from Gilenya to Rituximab
"This phenomenon of severe disease reaction has been seen before after discontinuation of Gilenya. It is thought that because Gilenya is causing the sequestration of immune cells in the lymph nodes (namely B-cells), they are essentially hiding from other immune-modulating therapies such as rituximab.
After the initial dose of rituximab (which depletes all B-cells in circulation), these B-cells leave the lymph nodes and cause a severe inflammatory response.
To avoid this in the future, the team recommends that physicians consider administering a second dose of rituximab a few weeks after the first dose, in order to deplete B-cells as they egress from the lymph nodes.
“Repeated initial dosing may be a reasonable alternative in patients switching from fingolimod [Gilenya], as it allows for a longer period with sufficient concentrations of rituximab in the blood to kill off B-cells egressing from secondary lymphoid organs,” the team concluded."
"and lead to progressive forms of MS not responsive to DMDs?"
Unfortunately no DMT is responsive to progressive or call it advanced MS. Neurologists(all doctors) love to give drugs as it makes them feel less useless and can pretend they are doing something to help. But the graphs don't lie..google Ocrevus vs. placebo if you dare.
Study finds multiple sclerosis drug slows brain shrinkage
10 pills a day for 2 years
48% reduction compared with placebo overtwo years
"The estimated rate of change in the brain parenchymal fraction was −0.0010 per year with ibudilast (95% confidence interval [CI], −0.0016 to −0.0004) and −0.0019 per year with placebo (95% CI, −0.0025 to −0.0013) (Fig. 1). This represented an absolute difference of 0.0009 per year (95% CI, 0.00004 to 0.0017; P = 0.04), or approximately 2.5 ml less brain-tissue loss with ibudilast than with placebo over a period of 96 weeks, and a relative difference of 48%.
I'm in a dilemma. I've been on Tysabri for 4 years now…JCV + of 0.25 titre for which I take an MRI every 4 months. Alemtuzumab came up in my last discussion with my neuro. He provided me with the facts and it's my choice to switch. I have a few questions though (and not too sure if they are the right ones to ask too 🙁 )
(1) Has there been a head to head study between Alemtuzumab and Tysabri? If not, what is the update in terms of reduction in relapses and brain athropy? (2) Has there been an update in terms of PML risk whilst on Tysabri? (3) They proposed that Il'l switch the following month to Alemtuzumab from Tysabri but what is the probability for a rebound to kick in before Alemtuzumab takes effect?
I understand it's my choice, but there is so much data and so little that I'm a bit lost. If Im doing well on Tysabri why should I switch? MRIs are good and I feel good at time. But then again, I am JCV positive, I have my bad days when I cant concentrate, I have to go into hospital once a month, MRIs every 4 months, and maybe Alemtuzumab will have a better impact with what can not be seen on MRI scans?…
Head to Heads of highly actives could be considered to be commercial suicide when your product is worse, so most of the head to heads are highly active against low efficacy.
All there is would be real life data but the demographics are unlikely to be properly matched.
2) Yes maybe profG will do this VV has been asking for ages
3) It is important to check for subclinical PML before depleting with alemtuzumab as there is no way back once the lymphocytes are back.
4) once you are JC positive and have been treated for 2 years you risk increases
Your cautious attitude toward switching from Tysabri to Alemtuzumab is understandable and quite wise, IMO. Gather all the relative information you can, get advice and counsel from those you trust, professionals and loved ones, then make your choice based on what fits you best; something you can sleep with at night.
May I make a couple comments? First, your JCV titer number is .25. A titer number between .2 and .4 is "indeterminate". It cannot be determined with accuracy that you are even JCV +. In any case, the number is extremely low and PML cases with very low JCV titers are rare, as I'm sure you are aware.
You are probably aware that extending time between doses of Tysabri was shown to reduce PML risk as the following article indicates…
Lastly, you mentioned you are doing well on Tysabri. My wife recently switched from Tysabri which was working as well as a cure for her, to Ocrevus. She is not doing nearly as well on Tysabri. Yes, everyone responds individually. But that shouldn't preclude those who switch DMTs from speaking about personal results of having done so.
Alemtuzumab has a host of potential side effects you need to be aware of, also, IMO. Do your homework.
Don't rush your decision. Be thoughtful, methodical and you will do just fine in making the treatment decision which best fits you. Nothing is more murderously difficult than treatment decision in MS.
hello, I'm wondering what you make of this study Alemtuzumab-Induced Thyroid Dysfunction Exhibits Distinctive Clinical and Immunological Features (https://www.ncbi.nlm.nih.gov/pubmed/29878256).
For me it is interesting because I have thyroid dysfunction following treatment (11 months post last infusion) but I certainly wouldn't describe it as "indolent".
I have both antibodies for Graves and Hashimotos. First diagnosed with Graves, then within 10 days of medication became overtly hypothyroid. And I could easily switch back to Graves again.
Back to the 'indolent' description, I had most of the symptoms of Graves and now most of the symptoms of Hashimoto's. Hardly indolent, much more fatigue and pain for starters.
As for the advice received telling me it's not so bad it you get a thyroid problem prior to commencing Alem, if i'd known just how awful it actually can be, I doubt I'd have taken this option.
Hi I see that the ORATORIO-HAND trial is soon to start and some sources suggest that Barts will be involved in the UK – other sources suggest no UK centres – please could you clarify if UK is involved in this trial – thanks
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.
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
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
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
MS was around along time before surgical mesh was invented.
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.
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
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?
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"
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
I guess we have been saying this for years. The correlations although highly significant need a programme to draw rather than being intuitive
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
Years old…I think the conclusion was they were safe…but nothing convincing about efficacy.
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
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:-(
What is the publication frequency and timing of new posts? It use to be 1pm daily but doesn’t seem to folllow that anymore?!
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.
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.
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
"At post mortem most people with MS have active lesions"
Then why not showing up on MRI's..?
Can the G comment on this?
https://www.ncbi.nlm.nih.gov/pubmed/30090637?dopt=Abstract
I will comment. The title is misleading we are talking about the CRAB drugs, not current DMT. CRAB drugs are simply no efficacious enough
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
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.
"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
…What does..
🙂
MD, how about a quest post by Dr. Franz Schelling? It is very easy to contact him.
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
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.
"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.
"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
Not adequatedly framing your work in the context of what is known from the work of others by deliberately ignoring it it with the view of deceipt to make your work look better, is in my opinion bad science and I dont care who it is.
Indeed sadly it is often the demi gods of science that do this to up the importance of their work. A sad fact of life.
PS John Prineas has a excellent reputation, but I have heard people question the finding about the early lesion.
🙁
I have this feeling that the research community dont tslk to each
other
Or talk to the ones that accept their views
That makes for herd mentality which is not good for science
development
Obrigado
Consecutive Use of Gilenya and Lemtrada Causes Disease Activity in MS Patient, Case Report Suggests
https://multiplesclerosisnewstoday.com/2018/08/21/high-ms-activity-seen-patient-after-consecutive-use-immunotherapies-case-report/?utm_source=Multiple+Sclerosis&utm_campaign=9f9e18055b-RSS_NON-US_EMAIL_CAMPAIGN&utm_medium=email&utm_term=0_b5fb7a3dae-9f9e18055b-71699829
https://www.ncbi.nlm.nih.gov/pubmed/30114625
Obrigado
Brain Health=Heart Health
Striving for Ideal Cardiovascular and Brain Health
It Is Never Too Early or Too Late
Better heart better brain
Several lines of evidence suggest that improved control
of cardiovascular risk factors is a substantial contributor
to declines in dementia.
The 2 reports in this issue of
JAMA
draw on the influential Life’s
Simple 7 cardiovascular health metric from the American Heart
Association (AHA), which is being used to measure and pro-
mote individual- and population-level improvements in car-
diovascular health.
11
With contributions from 4 modifiable
health behaviors (nonsmoking, healthy diet, physical activ-
ity, and body mass index) and 3 modifiable biological health
factors (low blood pressure, low cholesterol, and low fasting
glucose), the score indicates the degree to which an individu-
al’s alterable health factors are in accord with ideal cardiovas-
cular health and optimal cerebrovascular and brain health.
1
https://jamanetwork.com/journals/jama/article-abstract/2697677
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Final nail in the coffin of.barts theory of only.one TYPE of MS? Speak this explain Progressive MS?
https://www.sciencedaily.com/releases/2018/08/180821185244.htm
Thanks for the post. The paper was recently published in Lancet by the team from the Cleveland Clinic. This subtype of MS is independent of white matter degradation and involves neuronal cell death as the predominant pathology.
Maybe MS is still one disease but instead of demyelination neuronal cell death is the initial pathology. It seems that the individual's immune response dictates the subtype of MS. Is there a robust adaptive immune response that is responsive to the B and T cell DMDs? Or does neurodegeneration occur independently of lymphocytes and lead to progressive forms of MS not responsive to DMDs?
Also why not comment on breaking news as the article? Let patients now your views whether take or real breakthrough? Can be weekly if need be. Surely as researchers u will be eager to give your opinion. Instead of patients bringing the news to barts.
Patients bringing news to us…why not pwmS have been doing this for years.
Many years ago NMO was called Devics MS, there is Marburg MS, Balos MS etc etc
I am away and have not seen the article. Neurodegeneration without evidence of demyelination. I have seen this in EAE loads of times.
In peripheral nervous disease you get bands of bungner where the transected axons repsprout down the old myelin sheath.
One swallow does not make a summer and if I make a section and find neurodegeneration in one part of the brain could it not be that the damage was some distance away and you had death of a nerve somewhere else.
Wallerian degeneration
https://en.wikipedia.org/wiki/Wallerian_degeneration
Wallerian degeneration due to denuded axons but here they find cortical neuronal loss in the absence of white matter involvement.
"but here they find cortical neuronal loss in the absence of white matter involvement."
Not sure. But is maybe the axon more sensitive/vulnerable to
a hostile environment than the myelin is..?
In the oven does the hot dog cook first or the bun..? Someone test this out please.
If after two courses of lemtrada there is still worsening of the disease why is there no pressure being put on nice to approve further treatments? What is happening to those patients? Are they simply having no further treatment for the disease or are they having other already existing treatments or are they waiting for ocrelizumab?
Based on the inability to access more treatments than the two initial treatments are neurologists not prescribing lemtrada?
I dont know it is clear that a significant numebr of people that need a third course
I hope I'm right in saying that it is possible to have a third round of Alemtuzumab on the NHS.
Recall, I think, ProfG posting as much and my neuro told me, in June, that she didn't have it there in writing to prove it to me, but to all intends and purposes it's a done deal, if I should need another treatment.
Metabolic Dysfunction and Peroxisome Proliferator-Activated Receptors (PPAR) in Multiple Sclerosis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032172/
Recent study from my doctor research group
🙂
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Case Study Suggests Need for New Treatment Strategy When Switching from Gilenya to Rituximab
"This phenomenon of severe disease reaction has been seen before after discontinuation of Gilenya. It is thought that because Gilenya is causing the sequestration of immune cells in the lymph nodes (namely B-cells), they are essentially hiding from other immune-modulating therapies such as rituximab.
After the initial dose of rituximab (which depletes all B-cells in circulation), these B-cells leave the lymph nodes and cause a severe inflammatory response.
To avoid this in the future, the team recommends that physicians consider administering a second dose of rituximab a few weeks after the first dose, in order to deplete B-cells as they egress from the lymph nodes.
“Repeated initial dosing may be a reasonable alternative in patients switching from fingolimod [Gilenya], as it allows for a longer period with sufficient concentrations of rituximab in the blood to kill off B-cells egressing from secondary lymphoid organs,” the team concluded."
https://multiplesclerosisnewstoday.com/2018/08/23/switching-from-gilenya-to-rituximab-for-ms-may-be-problem-case-study/?utm_source=Multiple+Sclerosis&utm_campaign=bd2dd1c32c-RSS_NON-US_EMAIL_CAMPAIGN&utm_medium=email&utm_term=0_b5fb7a3dae-bd2dd1c32c-71699829
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"and lead to progressive forms of MS not responsive to DMDs?"
Unfortunately no DMT is responsive to progressive or call it advanced MS. Neurologists(all doctors) love to give drugs as it makes
them feel less useless and can pretend they are doing something to help.
But the graphs don't lie..google Ocrevus vs. placebo if you dare.
https://wol-prod-cdn.literatumonline.com/cms/attachment/4fa98c21-f06c-45c9-b788-073e43220b4e/acn3377-fig-0001-m.jpg
https://onlinelibrary.wiley.com/doi/full/10.1002/acn3.377
Beeing that CVD is important in everyone its also a comormidity for pwms
Beware of those wrinkles
https://medicalxpress.com/news/2018-08-deep-forehead-wrinkles-higher-cardiovascular.html
Obrigado
Rosehip neuron
Scientists identify a new kind of human brain cell
https://medicalxpress.com/news/2018-08-scientists-kind-human-brain-cell.html
Myelin Repair in the Brain
http://www.jneurosci.org/content/38/32/7088
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For all ppms/spms patients
Ibudilast
Study finds multiple sclerosis drug slows brain shrinkage
10 pills a day for 2 years
48% reduction compared with placebo overtwo years
"The estimated rate of change in the brain parenchymal
fraction was −0.0010 per year with ibudilast
(95% confidence interval [CI], −0.0016 to
−0.0004) and −0.0019 per year with placebo
(95% CI, −0.0025 to −0.0013) (Fig. 1). This represented
an absolute difference of 0.0009 per year
(95% CI, 0.00004 to 0.0017; P = 0.04), or approximately
2.5 ml less brain-tissue loss with ibudilast
than with placebo over a period of 96 weeks,
and a relative difference of 48%.
https://medicalxpress.com/news/2018-08-multiple-sclerosis-drug-brain-shrinkage.html
DOI: 10.1056/NEJMoa1803583
🙂
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ta
?????
O que isso??
ta = thank you
Lolll
In portuguese tá=ok
🙂
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I'm in a dilemma. I've been on Tysabri for 4 years now…JCV + of 0.25 titre for which I take an MRI every 4 months. Alemtuzumab came up in my last discussion with my neuro. He provided me with the facts and it's my choice to switch. I have a few questions though (and not too sure if they are the right ones to ask too 🙁 )
(1) Has there been a head to head study between Alemtuzumab and Tysabri? If not, what is the update in terms of reduction in relapses and brain athropy?
(2) Has there been an update in terms of PML risk whilst on Tysabri?
(3) They proposed that Il'l switch the following month to Alemtuzumab from Tysabri but what is the probability for a rebound to kick in before Alemtuzumab takes effect?
I understand it's my choice, but there is so much data and so little that I'm a bit lost. If Im doing well on Tysabri why should I switch? MRIs are good and I feel good at time. But then again, I am JCV positive, I have my bad days when I cant concentrate, I have to go into hospital once a month, MRIs every 4 months, and maybe Alemtuzumab will have a better impact with what can not be seen on MRI scans?…
Head to Heads of highly actives could be considered to be commercial suicide when your product is worse, so most of the head to heads are highly active against low efficacy.
All there is would be real life data but the demographics are unlikely to be properly matched.
2) Yes maybe profG will do this VV has been asking for ages
3) It is important to check for subclinical PML before depleting with alemtuzumab as there is no way back once the lymphocytes are back.
4) once you are JC positive and have been treated for 2 years you risk increases
Hello,
Your cautious attitude toward switching from Tysabri to Alemtuzumab is understandable and quite wise, IMO. Gather all the relative information you can, get advice and counsel from those you trust, professionals and loved ones, then make your choice based on what fits you best; something you can sleep with at night.
May I make a couple comments? First, your JCV titer number is .25. A titer number between .2 and .4 is "indeterminate". It cannot be determined with accuracy that you are even JCV +. In any case, the number is extremely low and PML cases with very low JCV titers are rare, as I'm sure you are aware.
You are probably aware that extending time between doses of Tysabri was shown to reduce PML risk as the following article indicates…
https://www.mdedge.com/neurologyreviews/article/162420/multiple-sclerosis/extended-interval-dosing-natalizumab-associated
Lastly, you mentioned you are doing well on Tysabri. My wife recently switched from Tysabri which was working as well as a cure for her, to Ocrevus. She is not doing nearly as well on Tysabri. Yes, everyone responds individually. But that shouldn't preclude those who switch DMTs from speaking about personal results of having done so.
Alemtuzumab has a host of potential side effects you need to be aware of, also, IMO. Do your homework.
Don't rush your decision. Be thoughtful, methodical and you will do just fine in making the treatment decision which best fits you. Nothing is more murderously difficult than treatment decision in MS.
hello, I'm wondering what you make of this study Alemtuzumab-Induced Thyroid Dysfunction Exhibits Distinctive Clinical and Immunological Features (https://www.ncbi.nlm.nih.gov/pubmed/29878256).
For me it is interesting because I have thyroid dysfunction following treatment (11 months post last infusion) but I certainly wouldn't describe it as "indolent".
I have both antibodies for Graves and Hashimotos. First diagnosed with Graves, then within 10 days of medication became overtly hypothyroid. And I could easily switch back to Graves again.
Back to the 'indolent' description, I had most of the symptoms of Graves and now most of the symptoms of Hashimoto's. Hardly indolent, much more fatigue and pain for starters.
As for the advice received telling me it's not so bad it you get a thyroid problem prior to commencing Alem, if i'd known just how awful it actually can be, I doubt I'd have taken this option.
Hi I see that the ORATORIO-HAND trial is soon to start and some sources suggest that Barts will be involved in the UK – other sources suggest no UK centres – please could you clarify if UK is involved in this trial – thanks
ProfG leading on this i think
thanks – any idea of best way to try and get considered for this trial / contact ProfG would be gratefully received.