Monday, 22 December 2014

ClinicSpeak: What is the definition of high versus low lesion load on MRI?

Time is brain: what is a high-lesion load on MRI? #ClinicSpeak #MSBlog #MSResearch

"In response to a question from yesterday; what is the definition of a high lesion load on MRI? This is based mainly on data from the so called Queen Square CIS (clinically-isolated syndrome) cohort. These CISers had MRI at baseline and have been followed for over 20 years. The picture below show  a survival analysis of time to EDSS 3.0 or higher (non-benign MS); it is clear the CISers with more than 10 lesions do worse. CISers with no lesions at baseline do the best with very few becoming disabled; in fact 80% of this group never go onto develop MS and hence are unlikely to have MS."


"What is the difference between a CISer sith say 2 lesions at baseline and somebody with 20 lesions? Almost certainly the person with 20 lesions has had the disease longer, with a longer asymptomatic period during which time subclinical inflammation has been shredding their reserve capacity, hence the poorer prognosis on average. Another way of looking at this data is that someone with CIS who presents with a low lesion load is luck in that one of their initial or early lesions has caused symptoms before too much damage has occurred allowing them the possibility of starting DMTs early and giving them a greater chance of becoming NEDA. This strategy of using DMTs as a preventative treatment to preserve reserve capacity and delay all subsequent disability outcomes is not practiced by all; many MSologists, particularly in  the UK, would prefer to allow CISers or MSers to acquire more lesions before starting DMTs. These MSologists often quote that many MSers turn-out to have benign disease hence we need to wait for their disease to progress before treating them. The problem with this argument is that the damage that is acquired whilst waiting is irreversible, reduces reserve capacity and hence shortens their time to future disability end-points. In addition, benign MS is a moving target; the longer you follow benign MSers the smaller the proportion who remain benign."

"So if  you have more than 10 lesions at baseline this is generally considered a high lesion load. The lesion load does not tell the whole story. Some lesions are more destructive than others; the destructive lesions leave behind black holes on the so called T1-weighted scans. Similarly, lesions occurring in the posterior fossa or back of the brain cause more disability than those in the so called superior tentorial compartment of the brain. Active lesions, i.e. those with gadolinium enhancement are also associated  with a poorer outcome compared to inactive lesions. Finally, if there is already end-organ damage with overt brain atrophy this is associated with a poorer prognosis. Therefore, assessing prognosis on MRI is more complicated  than simply counting the lesions."

Table of poor baseline prognostic factors on MRI

  1. High-lesion load (>10 lesions on T2-weighted images)
  2. Presence of gadolinium-enhancing lesions
  3. Posterior fossa lesions
  4. Hypointense lesions on T1-weighted images (black holes)
  5. Overt brain atrophy (end-organ damage) 
"If you have any questions about your MRI scans you should ask your neurologist to go through them with you. Please note if you have a bland looking baseline MRI, with a good prognostic profile, you should consider yourself lucky in that your MS has presented at an early stage before you have acquired any damage. This means that with appropriate monitoring and/or treatment you can potentially preserve your brain's reserve capacity. On the other hand if you have a poor baseline MRI prognostic profile you will need to take your treatment decisions more seriously and have less time to play with. Please remember the dictum 'Time is Brain'."

CoI: multiple

26 comments:

  1. Prof G as always you seem to be promoting treatment; why don't you give a balanced view.

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    1. Re: "as always you seem to be promoting treatment"

      Yes, that is correct. I class myself as a treatment activist. Why wouldn't you treat active MS? I am not aware of many diseases that you wouldn't treat early and aggressively to prevent damage and a poorer outcome? The only one that comes to mind is prostatic cancer in elderly men; often the treatment is worse than the disease. I suppose you could make the same argument for MS. However, whether or not the treatment of MS is worse than the disease is an individual call and is for MSers to make not me. It is all about choice; informed choice. If you think I am not giving a balanced view that is okay; this is a blog and I giving my opinion. Please note my conflicts of interest; a large part of my job is MS DMT development and yes, I have many conflicts.

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    2. Prof G, I am also of the opinion that this blog is becoming too propagandistic of the virtues of DMTs that may or may not combat MS disease activity. It's all you're talking about without ever providing insights into why DMTs may fail or, at worst, cause serious complications. There is no guarantee that DMTs can fix MS damage, yet the way you campaign for them is almost surreal.

      Also, good luck trying to get most neurologists to take the time to go through MRI scans with us. Most cannot wait to get you out of the door.

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    3. Re: "...propagandistic"

      Have you read our posts on the Charcot project? I really don't think MS is an auto-immune disease, but is rather triggered or driven by a viral infection. What most of the DMTs do is simply stop the bystander damage that is occurring from the inflammatory response to the underlying cause of the disease. However, some of the DMTs may be targeting the cause of the disease. It is difficult to deny, or ignore, the evidence for the above.

      I am not sure has this position is compatible with your claim of propaganda (definition = information, especially of a biased or misleading nature, used to promote a political cause or point of view).

      Like all things, you need to read consider, accept or reject; nobody with MS has to go onto DMTs if they don't want to.

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    4. Re: "However, some of the DMTs may be targeting the cause of the disease."

      If that were the case then these DMTs will definitely cease PPMS progression, which the don't. These drugs are not as efficacious as you suppose they are. At least that is my unqualified opinion.

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    5. I just have to disagree with the “treatment propaganda” criticisms levelled at Prof G and the Team. This blog is THE most informative resource available that I have been able to find anywhere on the internet – and believe me – I’ve searched high and low. Nearly every other site is either pure gobbledygook science which I have no hope of comprehending, or is full of nice little motherhood statements based on standard drug company issued information. Many of the MS Organisations around the world have excellent websites, but they cater to people who want or need a much more basic level of information than I want. Team G’s site helps me make some sense of the research (even though so much of it is still way over my head) and the explanations offered by the Team do help to de-mystify some of the research.

      I have learnt so much since I found this site a few months ago, and have spent many hours sifting through the archives finding out more (especially from the Clinic Speak articles) about this crappy disease which has changed my life forever. Prof G and the Team are entitled to their viewpoints on treatment options, but I applaud their non-sycophantic commentary which accompanies many of the articles they post. There are many other sites promoting other perspectives such as various dietary and/or naturopathic approaches to treating and managing MS, and I keep a critical eye on those as well.

      For Anon at 11:37am – there are plenty of posts from Team G on why DMTs may fail, or cause serious complications, and at least Team G does suggest some signs to watch out for, as well as criticism on the lack of research done to identify those who may be non-responders. However, I must agree with you about neurology appointments not being long enough to look at MRIs – in my country a review appointment is 15 minutes long – no hope of looking at an MRI in that time if you want to have any meaningful discussion about other matters with the neurologist. And because our health system is so overloaded, you’ve usually had to sit and wait for up to two hours after the booked appointment time to get through the door of the consulting room.

      I may not necessarily agree with the postings or viewpoints put up on this site by both Team G and other contributors, but thanks to this blog I do feel so much more empowered to make my decisions with a broader understanding of the potentially good or bad ramifications of the choices I make. And each person reading the posts and comments on this blog can choose to agree or disagree with the content – what’s that old saying along the lines of “I may disagree with everything you say, but will defend to the death your right to say it”………..

      CoI – I am a person with MS, and I have had significant problems with the DMT I was prescribed

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    6. As an aside, my father died of prostate cancer earlier this year at age 89. When they diagnosed him 10+ years ago, they said something else will get him before the cancer. But nothing did. So, if I was elderly with a prostate cancer, I'd push for treatment for that too!

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  2. To people still in denial ( both MSologists and MSers): the path of MS is so unpredictable, that the longer a doctor works in MS the more humble they are about predicting the future/talking about prognosis. Some MSers have lesions in the brainstem and do well, some have very few lesions and are very disabled.
    Unpredictability is part of MS. And it is a problem for newbies in MS, a doctor seeing a patient "do well" for 10 or even 20 years without treatment may feel well about their great "therapy" choice. The next 10 or 20 years are a nightmare for most MSers (some lucky few escape with the so called "benign" MS - maybe they even didn't have MS to start with). By the time the MSologists in denial learn this, their career in medicine is nearly over.
    In my case it was not the neurologist who was in denial, it was me. Just as dangerous. :-/

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  3. Suppose somebody has PPMS with no relapses and no enhancing lesions.

    Does the lesion load have any relevance to anything?

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    1. “Does the lesion load have relevance to anything?”
      I can understand that location of lesions is significant in what impact they have and based on that a higher load does not necessarily meant greater disability, but some additional clarification from Prof G would be useful here. With the benefit of hindsight I can see that my MS started more than eight years ago, but I’ve never had a relapse and was only diagnosed last year when my functioning had become so bad it was clear there was something very wrong – but still no relapses or acute episodes occurring. (I’m “officially” EDSS 3.5 but that score does not take into account my very poor walking performance)

      The above from Prof G refers a lot to CISers as that is what the study was based on. However, is the data on lesion numbers still relevant for other MSers with PPMS if the date of their diagnosis is taken as being the “equivalent” of the CIS baselines noted above?

      This is all a bit scary, as my first MRI report only noted “numerous” lesions, with the biggest being about 1cm in size, and there were three big nasties in my cervical spine (and spinal lesions are not mentioned in the article above). That doesn’t leave me much leeway, as I’m obviously >10 lesions already. And I have no idea as to whether I have any active lesions because I’ve never had a Gadolinium scan – that’s due to happen early next year.

      Don’t get me wrong – I think Prof G’s article is really informative, but maybe we could have a bit of clarification to make its content clearer and more relevant for many of us.

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    2. Re: "Does the lesion load have any relevance to anything?"

      What you see on MRI is the tip of the iceberg; most lesions are microscopic. In addition, we don't do spinal cord MRIs. In general PPMS is predominantly a spinal cord disease.

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    3. Why do you not do spinal cord MRIs? Surely both neurologists and patients would want to know about anything that's lurking outside the brain, if only to at least have a complete picture of lesion numbers and status? Additionally, the radiologist reports on my MRIs have included comments about any other physiological findings which could potentially be a cause of symptoms such as any canal stenosis which could be pinching nerves etc (which they aren't)

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  4. This graph is baffling. Is this information based on history dating back to 1999 before there were high efficacious drugs such as tysabri, Lemtrada?
    In other words, if someone has 20 lesions but are on a high efficacy drug, would that graph still suffice?

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    1. Re: "In other words, if someone has 20 lesions but are on a high efficacy drug, would that graph still suffice?"

      No not at all. This graph only applies to the pre-DMT era and is simply a guide. I am sure things are very different now.

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  5. This is good information, I really enjoy your blog. I am a 28 year old male and live in the US and was just diagnosed with RRMS eventhough I've only had one attack, which was minor (facial burning/tingling). The baseline MRI showed 10 lesions most periventricular. One was on the Left Superior Cereberral Peduncle. Also, two T1 "black holes", no gad enhancements. I have some residual tingling/burning that can occur on any spot of my body.

    The first specialist I saw characterized my MRI as mild and recommended I go with GA or Fingolimod. The second specialist gave me a choice of any of the injectables and orals approved by the FDA.

    My main concern is when I ask these neuros about prognosis. The first one told me, "oh yeah, you'll be fine, you'll live a normal life" and the second neuro did not want to predict what could happen, he said it is too variable.

    How am I supposed to make the treatment decisions when the "specialists" dodge the prognosis question.

    From the looks of it, I have some good and bad prognostic indicators. Its been nine months since my first attack and I feel great, like I don't even have MS.

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    1. The first neurologist said what we all want to hear ( people pleaser), the second was probably closer to the truth - nobody knows, MS is unpredictable. Some factors are considered "good" prognostically, some factors are considered "bad" on average/statistically, but each MSer is different.

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    2. Re: "From the looks of it, I have some good and bad prognostic indicators. Its been nine months since my first attack and I feel great, like I don't even have MS."

      Excellent, but you need to get an MRI study to make sure you don't have subclinical activity. A lot of MS disease activity occurs below the surface.

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    3. You are lucky you feel great like you don''t have MS. If I was in your position I would take up meditation daily for the health benefits.

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  6. Does the EDSS actually go down at 15 and 20 years for the patients with higher lesion load? What's wrong with this graph?

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    1. Re: "Does the EDSS actually go down at 15 and 20 years for the patients with higher lesion load? What's wrong with this graph?"

      The 20-year study had better follow-up. The study subjects that were missed at 10 years and recalled at 14 and 20 years did better.

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    2. Thank you - that is good news, for a change :-). And please keep up the good work in the new year. All the best to Team G!

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  7. What do you do in case of RIS with high lesion load?

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  8. The no lesion CISers seem to do ok until 20 years out - is this when spms/ppms hits for this group? Still not great if you were 30 at diagnosis. And it is a considerable jump down the spiral, with those people having been EDSS 0 for so long (with who knows what fatigue or cognitive impairment)

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  9. Thanks for this post its very helpful. Do you think treating for NEDA will ever become the norm when costs remain high and outcomes still variable?

    Wishing you all a Merry Christmas. Your blog is a much valued resource.

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    1. Treating to NEDA needs to be the norm otherwise we (or should i say neuros) are not doing enough.

      Will this be possible because of cost of drugs.....These high costs occur for as long as the system allows this to happen, I believe that there are cheap alternatives but the system needs to change to allow change.

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