Tuesday, 1 March 2016

ResearchSpeak: how to change your worldview in a day

The leukodystrophies have more in common with MS than I realised.  #ResearchSpeak #MSBlog #MSResearch

"Yesterday's primer meeting at Queen Square on the leukodystrophies, multiple sclerosis and other neurodegenerative diseases was an eye-opener. It demonstrated to me that MS had more in common with a lot of other diseases than I thought. My presentation (embedded below) is about how we define MS as a disease and how different it is as a biological entity, but my most important slide is Slide-37, which tries to illustrate that many neurodegenerative diseases share common pathogenic pathways and these are the important pathways to target to try and modify the disease course of several diseases. I common theme to all of these diseases is innate immunity and the microglial response."


"I was also mortified to discover that certain patients with familial Alzheimer's  disease have many manifestations that look like MS. This has led me to ask the question of how many MSers have comorbid Alzheimer's disease or in fact have a familial form of Alzheimer's that mimics MS. They are unlikely to be undiagnosed - once you are diagnosed as having MS removing the label is difficult. Cognitive impairment is so common in MS anybody developing a dementia will simply have it put down to MS dementia rather than Alzheimer's or another form of dementia."

"The good news is that I have made several new contacts from the meeting and have many new ideas on how to take things forward with regard to new potential research proposals. It was clear from the number of discussions I had after the meeting is that I need to write up the 'Definition of MS as a Disease' as a paper. It provided a philosophical framework from which to work from. My problem is where will I get the time from?"


23 comments:

  1. And how does EBV fit in all this?

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  2. But the similarity with Alzheimer's is not a new observation by any means. For example, the paper by Stys et al. (http://www.nature.com/nrn/journal/v13/n7/box/nrn3275_BX2.html)

    In this paper, close comparison was made with Alzheimer's, in accordance with the idea that MS is primarily a disease of neurodegeneration. It was even postulated that the main difference between MS and Alzheimer's is the age of onset of Alzheimer's - in older people, the immune system is too aged to mount a systemic inflammatory response.

    This, at least, is my understanding. And one of the many reasons for my personal antipathy towards the current "just bludgeon the immune system" drugs, which to me, are working at the wrong end of this disease. The right end might be EBV? But I digress.

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  3. But how do you explain the fact that some of the MSers like myself have very little cognitive problems in contrast to motor problems if it's the same as Alzheimer's?

    I've had MS for almost a decade now and managed to learn two new languages in the last three years and could beat many of my peers with my memory so how can it be like Alzheimer's?

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    1. I have asked myself the same question, as I - and other people with MS I know - have no perceptible cognitive issues thus far (and touch wood). Perhaps it depends on how long the damage has been going on for, where the damage is, whether repair mechanisms are still working, the level of education, diet, lifestyle, exercise...

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    2. You guys sound like you're living with PPMS. That's a different disease from the cognitively impaired RRMS condition.

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    3. Me too, I've had MS for decades, no cognitive problems. Kept working, good diet, healthy lifestyle and exercised. I've had my fair share of exacerbations, some severe. No treatment or DMTs.

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    4. I'm the first anon without the cognitive decline after approx. a decade - I've got diagnosed RRMS, that's my point.

      I also seem to get relapses and excarbations of symptoms during stressful episodes but remaind stable the whole time in-between motor-wise.

      I stopped taking DMTs and see no difference in my clinical situation whatsoever.

      I would start taking anti-virals if proven to be useful, though.

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    5. Neurological diseases have come a long way in understanding what is happening and even puzzle pieces as to onset's and to an extent possible triggers. Technology is helping move things faster. Deep scan MRI's and other tech will bring more fruits.

      However that said there are other factors that may well be literally unresolvable. The brain, nervous systems, cells all have forms of signaling chemical and/or electrical. Understanding the electrical side of things is just not possible now, may never be. The brain/body makes a supercomputer look like a childs toy.

      Many people I know had onset of MS during great stress, self-included. During stress many things happen within the body chemical and electrical. Stress is said to be avoided by patients who endure MS as apparently statistics show more flare-ups under stress. Same with me.

      Chemically things happen, electrically things happen. Might high stress end up flipping a virus "on" in neurons or might the immune system be misconstruing the changes as causal by an antigen and thus attack.

      Lots and lots of questions. My fiance who worked on neural network programming for some years believe at least at a rudimentary level it could be simulated. Fed different forms of inputs and we might see the cascade of network failure. Clearly the immune system is attacking for a reason(s).

      Onset of MS appears at least to have numerous entry points and a predisposition of risk factors.

      Understanding MS fully may never occur but that does not mean a focal point is not located where it can be halted. Every treatment available works in differing ways and differing targets. No single one is 110% effective for all people. Hence, none of them inhibit the cause of MS.

      Wiping out certain immune cells is like destroying an invading army. Sequestering them keeps them from crossing borders. Inhibiting signaling stops communications. None answer why my immune system on occasion declares war on my CNS cells.

      No research I have read explains why differing areas of the CNS are attacked. Optic nerves being one of the most common.

      A question my fiance' puts forward stems in the area of "is the immune system more intelligent or like a machine ordered" to tasking. The findings last year under more research of a brain/immune connection may well be a big part in the MS equation, mitigating it, whole nother' story.

      I am aware of no study of people enduring MS for example to just be sedate. And who wants volunteer for that?

      When I am highly stressed I get activity.

      An interesting item at ACTRIMS 2015 from an Australian Jr. Researcher said in PPMS they see immune cells just hanging around in the CNS.

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    6. Yes Yes I had my first relapse when I was highly stressed. Then my second relapse was very bad and I was again stressed. This saddens me.

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    7. My MS started and continues to present as mostly cognitive impairment - anxiety, depression, mood swings, brain fog, memory issues, paranoia, trouble concentrating etc. Sometimes I feel like a different person from one day to the next. I have no motor issues 3 years after diagnosis and probably almost 20 since it actually started.. To me this goes to show you that it's a highly variable disease/ syndrome.

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  4. As it stands MS looks more like a syndrome than a single disease. We once thought that NMO was a form of MS and we now know that was wrong. Most 'MS' will be MS as we understand it but some occasional cases will be a mimic.

    To differentiate alzheimer's and MS clinically may be difficult. Both are common enough and may co-exist. Should we brain biopsy people with MS if they dement in an attempt to diagnose a condition with no great treatment options?

    I'm sure you could dig up a junior co-author somewhere to help with drafting the paper....

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  5. MS is a syndrome, not a disease.

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  6. I dont know but for me this publication is clear: there can be a diagnostic confusion between MS and other diseases that have similar characteristics to it in general all neurodegenerative (who also is one of the characteristics of MS, par excellence).
    From what I understand Prof. G. noticed the similarity of symptoms/pathophysiological pathways of MS with other diseases, such as already addressed leukodystrophy and Alzheimer's disease. No wonder that since in a recent news about advances in the analysis of the human genome (GWAS) have been shown to genetically IN is a bit far from Parkinson's disease, but scientists were surprised by the genetic proximity to Alzheimer (changes genetic the Human Histocompatibility Complex appear to also be present). Furthermore it appears that both diseases show deregulation in calcium channels for example. Still Parkinson's disease also has similarities with MS as dysregulated pathways of alpha synuclein.
    Or similarity with neuromyelitis optics, where the confusion between the two diseases is even greater. I know a girl who was treated for 5 years as MS and were found out later by anti-aquaporin 4 examination that it was NMO. I know a very rare case of a girl who has ALS and MS, to get neuros distinguish one disease from another was very complicated ... Also this realization that many diseases share similar symptoms action and routes opened even greater way the possibility of reusing the drug for treatment of these ...

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    1. And Lyme's Disease also shares many symptoms of MS. Lyme's Disease has exploded in the US, and reliably conclusive diagnostic tool does not exist. Moreover, Lyme's Disease does not present for years - just like MS.

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  7. I'm confused how can MS be a syndrome and not a disease? I have RRMS.

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    1. This may help [or not ;-)]
      http://www.differencebetween.net/science/health/difference-between-syndrome-and-disease/

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    2. I always saw MS as a Syndrome, such as well the Guillain-Barré Syndrome is called, since it is unclear what the definite cause.

      There are risk factors involved in MS, but none of them was still in fact set to the exact cause of MS, such as certain viral and bacterial infections (it seems that EBV is quite involved in this), smoking, low rate of vitamin D, genetic factors, excess salt, sex (more in women), age (prevalent in younger)...

      To illustrate it better here is the simple concept of the Syndrome:

      Med. "Set of observable signs and symptoms in several different pathological processes, and no specific cause".

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    3. Interesting. Although I'm almost disappointed: "Disease" is a word one can say with an embittered hiss, befitting of MS.

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    4. You say syndrome,
      I say disease
      What we need is a cure,
      ASAP Please.

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    5. Nice one, MouseDoctor2! You can kind of sing it to Bob Marley's "Could you be loved".

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  8. Pof g in your last slide why do you say you can't identify people at risk of MS?

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  9. There is always the possibility that there are different strains of MS that pathologically speaking we haven't been able to determine the difference, why do a few people only have an inflammatory response on their spinal cord and not brain or vice Versa, why do some suffer cognitively and some don't? Why does mobility get effective at such different rates? Is it because every single human body is inidividual and so the wide target that this disease has just means that we all have the same disease but it effects us differently or is there different disease types within the bucket of MS, as mentioned NMO, SLE, Sarcoidosis are all similar in someways to MS, but are different.

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  10. It seems the most likely cause of MS and related diseases is a problem with the nervous system control over the immune system. After years and years and years of looking for an auto-antigen as well as a MS virus you would think a conclusion would be drawn.

    The notion that the immune system functions in isolation is not something that would be a design feature since all other systems are regulated by the nervous system.

    Some researchers are comming to this conclusion but I'm afraid they are in the minority.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986730/

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