As I understand it, NF-kappa B is an interesting and vital link in the inflammation chain of MS, including progressive MS. In Germany, extracts of _Urtica dioica_, the stinging nettle, ISD 23, are used for rheumatism (http://www.ncbi.nlm.nih.gov/pubmed/10606356). _Urtica doica_ is known to be a potent ihibitor of NF-kappa B (http://www.febsletters.org/article/S0014-5793%2898%2901622-6/abstract?cc=y)As someone with progressive MS (probably primary as opposed to secondary, but who knows and should it matter), I have begun to enjoy nettle tea and find it useful for soothing my sensitive bladder (no infection has ever been found, it seems prone to bouts of inflammation). Any ideas on nettle tea as an alternative therapy would be most welcome, and any information on why ISD 23 is not used - as far as I know - for MS so far.
Sorry - I meant "IDS 23", but you will know that. Happy new year, by the way, and thank you for the work you do.
Prof Mouse,could you please recommend very basic reading on biology for curious person, who got no biomedical education besides very basic school course of biology and chemistry. Just to be better oriented in subjects you are writing about.Many thanks in advance.
Why do I not read about slow motility as an MS symptom? I am asking because my daughter (a heart patient) is dealing with extremely slow motility. This is different from constipation where there is a blockage. This is when one's body simply takes an extremely long time to digest food and move it on down the track.This got me wondering with all the theories out there about MS starting in one's gut (where a lot of our immune system resides), why don't we see more of these problems in MS patients? I know it seems capable of slowing the rest of our body and minds. Are the nerves related to our digestive track some how immune to MS?
Re: "slow motility"I will look into this and get back to you.
Thank you. It is just reading up on MS symptoms, I see bowel issues mentioned, but they are generally constipation or incontinence. While slow motility has caused both symptoms with my daughter, the symptoms are the results of the slow motility condition which I expected to see reading up on MS. I have not found much in the way of research on slow motility and MS. In our efforts to deal with my daughter's constipation a few months ago our GI told us to try was Ex-Lax with a doubling of her normal miralax. Hours after taking the Ex-lax and having no noticeable reaction, we were giving her miralax through her g-tube when a dog hit our tube causing her g-tube to detach. Without a plug in the g-tube, all the miralax just given came out...along with the cube of barely chewed ex-lax. Her body had not begun to digest it in the hours between treatments. The potential for slow motility to cause problems with MS treatments seems plausible if we are not absorbing them. On the flip side if slow motility is not happening frequently in the MS population, why not? I have to confess, I have no idea how often motility studies are done, especially when such symptoms can easily be written off as "another MS symptom.". We are just lucky enough to have her GI case followed at Hopkins (in the U.S.) because of her heart condition. Note, she is not an MS patient. I am. I just try to learn what I can while treating her. Again, thank you.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62468-5/fulltextWife of Oscar Wilde with an enigmatic disease. It seems "when in doubt cut it out" was used quite often.
If no views / information on nettles (or other herbal / alternative remedies to reduce inflammation), a reliable, scientific source would be greatly appreciated. Perhaps they do more on this in other countries. As someone with progressive MS, apart from physiotherapy, I have abandoned the "establishment".
Think about re-engagng with the establishment,but I do not know anything about nettles, as with many herbal nutriceuticals and remidies there is insufficient evidence base to recommend anything..sorry
My statement was too abrupt: I _am_ engaged with the establishment, but - apart from physio - they cannot help me.Too little evidence = to few good studies, too little money / financial incentive = a real shame.
For Anon at 12:00Maybe try engaging with the "alternative establishment" - and give LDN a try. Despite the lack of clinical trials and scientific evidence acceptable to mainstream clinicians, there are a awful lot of MSers who do get benefits from LDN, even if they are not the dramatic results claimed by some. I have not had a "miracle cure" with LDN but it has given me better outcomes than the DMT I was lumbered with. Many MSers are reporting improvement in symptoms or halting of worsening symptoms, and the MRIs of many MSers who are taking only LDN are showing either no progression or reduced rates of progression. You have nothing to lose by giving it a go.
My mother was asking me today if glandular fever can cause white matter lesions (at the time of having the glandular fever infection). Have patients with glandular fever been MRI scanned when they are in the infection stage? I looked on the NHS page:Neurological complications of glandular fever:In less than 1 in every 100 cases, the Epstein-Barr virus (EBV) can affect the nervous system and trigger a range of neurological complications, including: Guillain-Barré syndrome – where the nerves become inflamed, causing symptoms such as numbness, weakness and temporary paralysis Bell's palsy – where the muscles on one side of the face become temporarily weak or paralysed viral meningitis – an infection of the protective membranes that surround the brain and spinal cord; although unpleasant, viral meningitis is much less serious than bacterial meningitis, which is life threatening encephalitis – an infection of the brainThese complications will often need specific treatment, but more than four out of every five people with them will make a full recovery.Secondary infectionIn a small number of cases, the initial infection weakens your immune system and allows bacteria to infect parts of the body. This is called a secondary bacterial infection.
Hello Team GCan you advise what the difference is between a standard MRI and a diffusion weighted MRI please? I've got an appointment for both, standard with and without contract and this new diffusion one. I've only ever had standard MRI's before and I'm a bit anxious as to what they are looking for with the diffusion one. I've googled it but cant make out the terminology.
When you have your car cleaned you can have the standard or the deluxe clean the car ends up clean but the deluxe is cleaner. You can have an MRI and you can get also a deluxe MRI...it is still a brain scan but in this case there is more information found and the scanning may take a little longer. It is good that your unit can do diffusion weighted MRI as it is not standard everywhere and the reason you are getting it now may be because the unit hasa better scanner or that they have established a robust protocol for diffusion weighted imaging. The standard with and without contrast agent will show new and old lesions this is T1 and T2 imaging and the gadolinium is the contrast agent so when this gets in the brain it will show active lesions.As to diffusion weighted MRI( http://en.wikipedia.org/wiki/Diffusion_MRI) it is essentially an advanced imaging technique that shows nerve tracts and may help see if there is nerve damage or not. You don't get these everywhere. It will tell your neuro more about your MS over an above what can be understood by standard scans. Take this as a plus as your neuro will know more about your MS and this may help their treamtent advice
Thank you MD. Cant see why I need a standard one if the diffusion does the same thing just better though. Shame MRI's don't work the same way as car valeting!
OK not quite right analogy the diffusion one is a special imaging technique they are not the same thing as the standard one as they give slightly different info, the diffusione one measures nerve tracts
I'd be curious to know what the reasons might be for why the 2 MRIs I've had before were done without Gadolinium, and now, six months after my last one, the neurologist has asked for one to be done with Gad. I don't know whether our local MRI machine does the DWI imaging or not, only that it can do 3mm and 4mm slice thicknesses
Every MRI done has a cost, gadolinium has a cost, and there are time issues relating to the acquistion of the scan. The more complex outcomes require longer to do and do you have the facilities to be able to analyse and read the scans. Why gadolinium or no gadolinium, there can be many reasons, maybe there was interest to check to see if you have no evidence of disease activity. Maybe there is a need to escalate your treatment options, maybe part of your check up..without knowing the circumstances you can read something or nothing into it.
From Anon at 5.28am - thank you MD. MRI No 1 done 18 months ago was supposed to show that I did not have MS - but it ruled MS in not out (lots of lesions including several spinal). I was told that MRI No 2 done 6 months ago was to check for progression, and as I had been on a DMT for the preceding 9 months I would have thought (within the bounds of my limited MRI knowledge, and because all of my symptoms were worse) that Gad would have been used for the 2nd MRI but it wasn't. Not currently on any DMT (side effects plus more side effects) and in our health system the specialists' appointments are so short that there is no opportunity to ask these sorts of questions, which tends to leave you feeling very left in the dark about the whys and wherefores of it all.(not exactly looking forward to a two hour stint in the noise factory, but a patient's got to do what a patient's got to do...... sigh)
If the symptoms were worse then maybe the neuro felt they didn't need gadolinium to tell them what your MS was telling them.I would have thought that if you were on a DMT and failing you need a stronger DMT if your disease will respond to it. There are no approved DMT for progression yet.
Is there a curriculum that trainee neurologists/ registrars follow? or is it up to the university hospitals to decide what is taught? I can see a few areas that need tweaking as regards to MS.
ABN, Association of British Neurologists.
I was watching a video today and it explained that around 95% of disease is triggered or caused by stress, or stress is a major factor in its development. Stress makes us vulnerable to infections. Not getting enough sleep and rest makes us not able to recover quickly from infections. Stress can cause fear.
Dear Prof G. My MS nurse informed me a month ago anxiety triggers relapses and is quite common. I find it very hard to understand why neurologists are not warning MSers about this and that stress can trigger relapses. Neurologists in my opinion should be offering CBT and stress management to MSers and those suspected of having MS as standard. I think you might of come to the same conclusion in 2013 or 2014. It doesn't make sense otherwise. Dr Gnanapavan mentioned that TNF alpha might be the missing link between stress and heightened MS activity. Would it be the same with an anxiety triggered relapse? It would be interesting to know what chemical/protein is released in the body in an anxiety triggered relapse. Anxiety can be severe is MS and it saddens me to know this as with meditation it can really reduce anxiety naturally but the meditation needs to be done twice a day, every day.
Re. Prof G's post on spine injurys/head injurys and MS. I had a nasty head knock and got euphoria for a few hours, then migraine next day. I told the trainee neurologist and his response was: he laughed at me and said to me if it feels that good why dont you do it again. He then laughed again at what he just said. He shook his head no to indicate it wasn't relevant to my first relapse. He didn't ask me if I a headache the next day and for some reason I forgot to tell him of my migraine. I wish now I went to A&E after that head knock. I can assure him I will not be doing that again. I feel that was quite inappropriate. I think it was very relevant to my first relapse.
Last year my spine became very sensitive. This happened after I travelled for an hour on a old bus, a bone shaker old bus that vibrated badly when the breaks were on. From that day onwards my spine was sensitive and tingling. Then my inner thighs started to tingle after I had been for a walk. Another MSer said to me that something must have pressed on a nerve in my spine on the bus. I feel my spine is deteriorating. I'm fine laying down or seated but when I stand I ache in my legs and back. I avoid the bus now if possible and I seem fine on the train.I wonder if any other MSer has had tingling after being on the bus?
I read on this blog that previous CDS inflammation can cause age-related neuro degeneration. I had l'hermittes following radiation for hodgkins in 1990 (age 25) which is quite common. Then when I was 45 had some numbness but clear MRI scan. Now at 50 drop foot and lesion at c3/c4. Clear brain MRI and negative LP. One neuro thinks it is possible PPMS and another says age related neuro degeneration from radiation. Tried a course of avastin and afterwards MRI was normal. Then tried fampridine - when down hill and lesion was back. After reading prof G report I am going to ask for simvastatin from my neuro.
I had memory loss during and for some time after a severe relaspe. I was also stressed and anxious and know these can also cause memory problems. Has any research been done on memory problems and relapses?? thanks
http://seattletimes.com/html/localnews/2025434042_msstemcellsxml.htmlHALT MS trial for patients who are RRMS and have "failed" conventional therapy. Can Team G elaborate on the concept of failure in patients with RRMS. I would think patients that have failed therapy and now have progressed (i.e. greater EDSS) are now SPMS. What is the distinction between sustained disability in SPMS and sustained disability in RRMS that is not responding to therapy? Would SPMS patients benefit from high dose immunosuppressive therapy and autologous stem cell transplant in that it would stop progression?
Sustained disability in SPMS and RRMS are I suspect the same thing as it is probably the same process driving both, but if you have RRMS superimposed on top the relapses can lead to disability also. At present SPMS who are more advanced continue to advance with this type of treatment so I would suspect it would not stop progression, who there be benefit this is possible as the immune response is still active in SPMS.
http://www.nytimes.com/2015/01/13/health/after-enterovirus-68-outbreak-a-paralysis-mystery.html?_r=1The Drs. could find no evidence of Enterovirus 68 in blood or CSF in AFM (acute flaccid paralysis). "Damage to the CNS grey matter may not be due to the virus but the immune response of the patient...."
Are there going to be some results published regarding to Charcot project?
Not yet,it has not all finished
Hoping and praying for good results�� sure your on the right path with herv and evb hvv6 theory! Just hope raltergravier is the right drug
Hola! Do you have an idea of which month we should expect to see Charcot results published on the blog?Thanks.
The day of the press release. News will be embargoed.
I've just been listening to podcasts and downloads on the BBC world site, Discovery from 8th December 2014 about the vagus nerve There is research ongoing into whether stimulating the vagus nerve reduces inflammation by reducing TNF. Someone is looking into it in respect of rheumatoid arthritis. It's already used as a treatment for epilepsy. Has it any relevance to MS, or is it just like CCSVI?
I was surprised that no one asked about this report, when the news was released, bout what would happen in MS. The simple answer is I don't know. There is a suggestion that stimulation will inhibit immune responses so it should work the. Howwever if the action is to block TNF, then this could make MS worse,as TNF blockade can make MS worse. It is not like CCSVI yet
Mouse Dr,Turmeric is in the news as a helpful cure for MS. Can you elaborate on this spice? How much Turmeric would you need to ingest?
If you see the four letter c word in the media (c***), the story is likely to be another 4 letter c word ending in p (c**p):-). I am not sure what the story is. Do you have a link? I found there was a claim that tumeric prevents remembering fear (in the Mail) and this links to an older story about stem cells. What doesn't it do?. There is a compound in the root called curcumin and this is claimed or believed to do all sorts of things, including getting rid of ebola.Lets go to the trusty EAE model and find the dose used to do something and they were using 200mg/kg (http://www.ncbi.nlm.nih.gov/pubmed/19539560) which scaled to a human dose is about 14g/day. As there is about 2% curcumin in tumeric apparently, so that equates to about 700g per day. So this is about the equivalent of eating 20 x 35g pots of tumeric powder a day..or 2 if you apply mouse/human scaling...need we say more about the likely reality of the claims:-).Rule 19 of the ARRIVE guidelines concerning reporting of animal work. What is the translatability of the work to humans....if the answer is none...don't start to do the work!.
Thank you for the link about the HSCT trials, but please read the top "Do not distribute", "Confidential" and "Embargoed". There is a media black out until the work is published. Some journals threaten to withdraw the manuscript if the embargo is broken However the story is online Association of Nonmyeloablative Hematopoietic Stem Cell Transplantation With Neurological Disability in Patients With Relapsing-Remitting Multiple Sclerosis. Burt RK,JAMA. 2015 Jan 20;313(3):275-284. doi: 10.1001/jama.2014.17986. and ProfG will no doubt do a post on this
MD,do you know why we need CFA to induce EAE in mice? Is there a known mode of action?
We need CFA to trigger an immune response against myelin antigens. The homogensed antigen and CFA acts as an antigen depot to sensitise cells of the immune system which then migrate to the CNS to trigger disease.
ProfG calls it the immunologists dirty little secret
Copyright Charlie Janeway.
Thanks for your reply! But since CFA contains lysated mycobacteria, why aren't these particles considered as a cause for MS in humans? Maybe HERV and lysated mycobacteria share a common mechanism, eg. a receptor.- A study in Nature found DC-SIGN (CD209) vessel associated dendritic cells in and around lesions."Notably, CD209+ cells were also found in noninflamed human brain tissue liningblood vessels, leading to the idea that they may act as the initial APCsrecognized by invading encephalitogenic T cells"http://www.ncbi.nlm.nih.gov/pubmed/15735653- DC-SIGN is the main receptor for mycobacteriahttp://www.ncbi.nlm.nih.gov/pubmed/12515819- HERV bind to DC-SIGN"Both the SU and SU-C proteins bound to DC-SIGN, although with different efficiencies, probably due to structural differences"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1082723/- DC-SIGN is involved in the initial stages of HIV infection. Maybe this is what makes people with HIV "immune" to MS?http://www.ncbi.nlm.nih.gov/pubmed/10721995- Vitamin D decreases expression of DC-SIGN (-> positive effect)http://www.tv3.cat/marato/docs/simposiums/marato01/eng/DrFibla.pdfDC-SIGN also serves as an adhesion molecule that binds to ICAM molecules e.g on endothelial cells. Nicotine enhances expression of adhesion molecules (-> negative effect)http://link.springer.com/article/10.1385/CT:6:1:39Besides blocking VCAM, Natalizumab also decreases ICAM. (-> positive effect)http://registration.akm.ch/einsicht.php?XNABSTRACT_ID=156437&XNSPRACHE_ID=2&XNKONGRESS_ID=171&XNMASKEN_ID=900
CFA contains heat-killed Mycobacterium tubercuolsis (and also butyricum in some cases) which acts as a chemoattractant/stimulator of immune cells which combined with antigen produces an immune response. For your theory to be correct you would expect to find an association between MS and TB which, as far as I can find, has not been demonstrated.
The connection between TBC and MS was established back in the 1920s.I found this in the german SPIEGEL from 1956 (excuse my poor translation skills :) ):"Just recently, two research groups from Austria and the USA have made important discoveries that could lead to the development of new therapies for Multiple Sclerosis. MS, according to the scientists, may be a late form of tuberculosis. The work of these independently working research groups confirms a theory that has been proposed by Dr. Herwig Ahringsmann back in the '20s."..."In 1935, Professor Heinrich Gerhartz said he found tuberculosis typical reaction in 54% of the serum from people with MS. With, 68%, neurologist Dr. Battner from Vienna even got a higher result.".."After WWII, american scientists Kurzke and Berlin discovered a possible connection between MS and TBC. The researchers treated a female MS-patient, who also suffered from tuberculosis, with the new pharmaceutical Rimifon. After a while, not only symptoms of TBC, but also MS, improved. Based on this discovery, Kurzke and Berlin treated 30 people with MS with Rimifon. And again, they were able to detect improvements in 27/30 patients".http://www.spiegel.de/spiegel/print/d-43062431.htmlAlso, a special strain of attenuated mycobacteria has been proposed as an MS vaccinehttp://multiple-sclerosis-research.blogspot.com/2013/12/bcg-vaccination-limits-development-of-ms.html
Sorry but there has been no well researched association between MS and TB. If there was you would expect the incidence of MS to decrease as a result of the rigorous TB eradication program in the UK post WWII. There has been no such decrease in MS incidence so I suggest any historical suggestions were bogus and there has been no association revealed in studies over recent decades.
1. Not all mycobacteria cause TBC2. You would only expect a decrease in incidence if mycobacteria were the only cause for MS, and I'm not saying that.HERV also bind to DC-SIGN, and while TBC might have been eradicated, EBV prevalence is very high and may therefore account for most of the cases. Exception could be areas like Sardinia with an unusual high rate of MS (where different studies from the last years connect mycobacterium avium with MS)But no worries, nobody believes me. Time to find the right topic for a PhD and prove you all wrong ;)
A very important and urgent question: Siblings and other first-degree relatives of MSers are at high risk of MS compared to the rest of the population. Based on current knowledge and educated guesses, what can they do to reduce their chances of developing MS?
All my relapses have been stress related. I purchased a book on CBT recently and there's a section on assertiveness. Ever since I was young I have been shy, unassertive and nervous around some people. I've come to the conclusion my stress triggered relapses are linked to me not being assertive enough. To be assertive means to get the result you desire but in a non agressive way. It's about thinking before you say and act. For me it's knowing when to walk away when something becomes a hassel. It's like me learning to say "thanks very much but it's not right for me". It's probably obvious to some/alot of people.
Anxiety can cause stress and stress can cause anxiety, it's bidirectional. Severe anxiety is common in MS and TNF alfa may be the missing link between stress and heightened MS activity. Also anxiety can result in heightened MS activity. Research is desperately needed in this area.
Prof G, What would you say to me if you suspected I had MS and I told you I was very stressed? I hope you would discuss stress with me, ask me questions about the stress, take some time over it. Unforunately this was'nt the case for me. The doctor wrote it down, we didn't discuss stress and why I was stressed, he changed the subject, was not concerned about the stress. I ended up having a pretty bad relapse. I didn't know then the stress was related to the symptom, I didn't know I had MS at the time. If he had handed me a blank piece of paper and pen and asked me to list all the things making me stressed and anxious (there were quite a few things), then discussed them with me this would have really helped me.
http://pubs.acs.org/doi/abs/10.1021/jf505075n?journalCode=jafcauOnce again the answer to many of life's most perplexing issues can be found in........the pub. "Bartender another round of neuro-protective polyphenols." Any volunteers for a clinical trial?:-)
Dear Dr Gnanapavan (and Team G), you highlighted something very important: the key is to recognise a relapse early and treat it. I mentioned this to my MS nurse and she is in agreement with you. But this is not common practice as far as I know. I had a left 7th nerve/facial palsy/bells palsy recently and from my experience, researching on the web I knew the 72 hour time frame when starting antibiotics could help the symptoms. I visited A&E, stayed in bed, slept alot and relaxed, tried to not get stressed and anxious. I had some dizziness which often goes with bells palsy. My face luckily recovered fully within three weeks without steroids. I really think this should be the new ethos amongst neurologists 'to recognise a relapse early and treat it'. It needs to be added to NICE guidelines for treating MS if it's not already. What you think?? thanks
I took five days of antiviral not antibiotics.
I fully agree. It really irritated me when there was this view that relapses do not matter to the fate of MS, going round the CCSVIers view of those dangerous MS drugs. I counter this by saying tell this to people who have a devastating relapse that these do not matter. The question is what to do. EAE shows us there are hundreds of agents that will quickly knock the response down but can they be better than steroids.Let us see what happens with the phenytonin trial. Everyone on the trial was put on methyl prednisolone, which would be the standard treatment for relapse. In the optic neuritis trial we were aiming to treat the inflammatory penumbra, i.e. the damage surrounding the inflammatory event. If people on the optic neuritis trial do better showing that it can protect the effects of relapse...the obvious thing that should happen is that this approach should be applied to clinical relapse because this is what optic neuritis is, a relapse in a defined location, treatment may only need to be transient and we could apply one of many generic agents for this, but phenytonin could be an obvious choice. We have treated hundreds of mice at relapse with a number of sodium channel blockers (phenytonin was not the best choice) and other targets and have found that they come out of the the other side in a better state with more nerves intact. Of course it would need a trial but if done across a broad network with enough people it should not be hard to do quickly..he says. We could add an extra arm to something ProfG has been thinking about
Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.