Saturday, 11 March 2017

Should we be debating

ProfG and his chums have been in Edinburgh for their Debating Society, whilst we were stuck with the mouse muck.

Not so long ago I was asked if I would like to Debate the Motion that "We should not be funding animal experiments?" 

  • I originally said that I would consider it, but said I was not going to try and defend the indefensible in the interests of a debate. 
  • In fact I would have been better placed to support the motion as I know where the achilles Heels are. 
  • However, I said that I rather resented the tone of the question. 

If you want to debate the merits of animal work there are less aggressive/inflammatory ways of doing it.

Why? You are asking me to judge whether others should be leaving science or moving on.

That the person posing the question was on grant panels and so deciding peoples fates, does not bode well. 

I said they should first approach some mechanistic immunologist who thinks MS is EAE, so they can defend their corner:-). 

This is surely where the debate is at, at the moment. 

Let them hang themselves (or not). However there are a number of people that voice this opinion...They are generally medics, but not always.

In the interests of balance I suggested that they should then run the feature on: 

"We should not be funding further imaging studies" 

"We should not be funding academic-led clinical trials" 

If we did this as a burining debate ast ECTRIMS, it would end up as a love-in.  Fund it all

Indeed these aspects are things that you have been asked to fund, especially as in many cases you want the trials to be undertaken.

Sure imaging has been also been instrumental in developing diagnostic measures, but has it really shown us the structural biology that we want?

At the population level, we have had prognostic features reported left, right and centre, but at the individual level they seem to mean nothing from a predictive stand point. I cringe at an r=0.05.

Don't understand r.  click below
http://multiple-sclerosis-research.blogspot.com/search?q=correlation

Imaging has generally failed to match to the pathology and it misses alot because it lacks resolution. 

A good example of this would be the fact that MRIers and the pathologists missed grey matter lesions for years. 

How can the animal models model when they are being told duff info in the first place :-(

Am I going to debate this....No

I'll let others do it.

Characterizing Clinical and MRI Dissociation in Patients with Multiple Sclerosis. Healy BC, Buckle GJ, Ali EN, Egorova S, Khalid F, Tauhid S, Glanz BI, Chitnis T, Guttmann CR, Weiner HL, Bakshi R. J Neuroimaging. 2017 Mar 6. doi: 10.1111/jon.12433. [Epub ahead of print]

BACKGROUND AND PURPOSE: Two common approaches for measuring disease severity in multiple sclerosis (MS) are the clinical exam and brain magnetic resonance imaging (MRI) scan. Although most patients show similar disease severity on both measures, some patients have clinical/MRI dissociation.
METHODS: Subjects from a comprehensive care MS center who had a concurrent brain MRI, spinal cord MRI, clinical examination, and patient reported outcomes were classified into three groups based on the Expanded Disability Status Scale (EDSS) and cerebral T2 hyperintense lesion volume (T2LV). The first group was the low lesion load/high disability group (LL/HD) with T2LV < 2 ml and EDSS ≥ 3. The second group was the high lesion load/low disability group (HL/LD) with T2LV > 6 ml and EDSS ≤ 1.5. All remaining subjects were classified as not dissociated. The three groups were compared using regression techniques for unadjusted analyses and to adjust for age, disease duration, and gender.
RESULTS: Twenty-two subjects were classified as LL/HD (4.1%; 95% CI: 2.6%, 6.2%), and 50 subjects were classified as HL/LD (9.4%; 95% CI: 7.0%, 12.2%). Subjects in the LL/HD group were more likely to have a progressive form of MS and had significantly lower physical quality of life in adjusted and unadjusted analysis. Subjects in HL/LD had significantly more gadolinium-enhancing lesions, and subjects in the LL/HD group had significantly more cervical spinal cord lesions.
CONCLUSIONS: Our results indicate that dissociation may occur between physical disability and cerebral lesion volume in either direction in patients with MS. Type of MS, brain atrophy, and spinal cord lesions may help to bridge this dissociation.



So a dissociation between clinical and imaging. Is the imaging fit for purpose?

What do you think? 

12 comments:

  1. OK , what do we see as lesions on MRI? Water, I would think. That could be different things - more inflammation in some cases... more repair in some other cases.
    We should image more, learn more about the underlying mechanisms before reaching any conclusions.( Well, pharma has reached some conclusions for us where it suits them - but are pharma guys always on track?)
    (I am one of those MSers with very heavy load on MRI right from the start and no obvious physical disability after 11 years ... although fatigue is absolutely draining. )

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    1. H'mmm. So at the start had 'at least 12' (well known fact, radiologists can only count to 12) spinal cord lesions (mainly cervical) then had very few problems for next four years (EDSS at most 1) so neuro no1 looked at my notes, stopped beta interferon and I happily told everyone my MS was mild. Pity neuro didn't also have a quick check of MRI and seen the multiple new lesions that had accrued. On the plus side did enjoy another 2 years with no injections, flu side effects or major MS problems.
      So 6 years, all good and am grateful to neuro no1 for that.

      Then came the (mainly sensory) relapse that I've never recovered from and today find myself worsening fast. New neuro actually looks at me, remembers who I am and says he doesn't need an MRI to tell him there are new lesions because of rate of obvious worsening.

      So after 11 years EDSS 6.0. Disability now very obvious, but the worst thing by far is still the totally invisible pain.

      Rant over.

      So far as the debate goes? Neuros look first at your patient/pwMS (not the notes) but if that's not enough look at the imaging (technology will only improve) and if necessary all the other useful diagnostic tools.

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    2. He/she does not need MRI? So how does she/he plan to follow it up, may I ask? Clairvoiancy :-)? reading from coffee grounds? If they do not know what is on MRI now, how would they know if anything changes in a year? I thought 2T2 (treat to target) was old news, even in neurology.

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    3. I have 10+lessions on the brain none on the spine ...I run 1/2 hour...
      Mri´s dont mean a thing (in my mind at least)
      IMUNE MONITORING SHOULD BE MORE RELIABLE

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    4. I have 10+ lessions on brain

      I run 1/2 hour
      Mri are like photographs.Dont tell much about yourself
      Imune monitoring is the key

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  2. Rumour has it the UK MS Debating Society were seen walking the streets of Edinburgh at 3am in the morning looking much wiser for having just debated the health benefits of alcohol.

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    Replies
    1. Hahaha! All the best debates take place then ;-)

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    2. Alcohol does travel.......................................... the blood brain barrier...lolllllllllll

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  3. I have LL/HD . I have always been puzzled by the dissociation and neurologists given me no satisfactory explanation. On MRI my only lesions are in the cervical spine (about 5 lessons). I have significant right leg disability which makes walking very difficult and am starting to get right arm and hand weakness. i have had no change in MRI for several years but my clinical symptoms continue to get gradually worse. I was diagnosed 19 years ago and had my first symptoms around 40 years ago (I am 67)

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    Replies
    1. Location, location, Location
      Where the lesions occur is of central important. The cervical cord is one of the areas where there is alot of nervous information passing through, so on lesion can have many consequences.

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    2. Am I correct in saying PPMS tends to be associated with more spinal lesions?

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    3. ....Like real state....Yoou know your lesson well...

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