Wednesday, 18 June 2014

Clinic Speak: brain damage and fatigue

Brain Health: has your neurologist discussed the issue of brain health with you? #ClinicSpeak #MSBlog #MSResearch

"The study below supports previous work in this area and shows that fatigue is linked to brain damage in MS; in particular certain areas of the brain. This makes sense. Our brains are wonderful machines and have built in extra capacity so called cognitive reserve. When one area of the brain is damaged other areas help by working harder and compensating for the damage. This compensation consumes extra energy and results in mental fatigue. This is why I believe that fatigue, in particular mental fatigue, early in the course of the disease needs to be taken very seriously and is a sign of structural brain damage. When mental fatigue is associated with a high lesion load and brain atrophy it is not good news for the MSer concerned."

"Brain reserve is something to cherish and look after; it is what protects us from  the ravages of ageing and allows us to maintain a good quality of life as we get older. I don't think we should be treating MSers any differently to the normal population hence the need to promote brain health. To keep your brain healthy you need to have good sleep hygiene, do physical exercise, not smoke, drink moderately (excessive alcohol is bad for your brain), eat a well-balanced healthy diet, make sure all comorbidities are diagnosed and well managed (obesity, hypertension, high cholesterol and diabetes), avoid contact sports associated with repeat head injuries and maintain your social capital (remain socially active). Some claim intellectual exercises, or brain training, promotes brain health; maybe - I am not convinced by the science of brain training yet. In the future we may be able to take medications to help with brain health; for example statins, hormone replacement therapies and aspirin."

"Brain health is one of the reasons why I have moved the goalposts from simply targeting NEDA (no evident disease activity) to preventing end-organ damage, i.e. normalising brain volume loss in MS. Therapeutic nihilists don't buy into this; they claim that the long-term data linking brain atrophy to a poor outcome in MS is indirect and we need to show that slowing brain atrophy is associated with a positive outcome. I don't think they will have to wait too long for the data supporting brain atrophy as a validated surrogate marker to emerge; some very interesting data on brain atrophy and clinical outcomes were presented at the EFNS-ENS meeting in Istanbul. For me slowing, or normalising  the rate of brain atrophy, over many years, is a no-brainer. Excuse the pun!"

"Last year I ran a campaign to redefine MS as a preventable dementia. I got a lot of stick about this campaign and was accused or of trying to stigmatize MSers. All I was trying to do is raise awareness about the issue of cognitive impairment in MS and that it occurs early in the disease and is probably what drives the early unemployment rates and results in fatigue, depression and anxiety. If MSers and healthcare workers took the issues of early cognitive impairment more seriously they may reappraise their position on early effective treatment and treat-2-target of NEDA to prevent end-organ damage."

"To assess brain health awareness, I would appreciate it if you could complete this short survey. Thanks."

Epub: Rocca et al. Regional but Not Global Brain Damage Contributes to Fatigue in Multiple Sclerosis. Radiology. 2014 Jun 14:140417.

Purpose: To use magnetic resonance (MR) imaging and advanced analysis to assess the role of lesions in normal-appearing white matter (NAWM) and gray matter (GM) damage, global versus regional damage, and atrophy versus microstructural abnormalities in the pathogenesis of fatigue in MS. 

Materials and Methods: Local ethics committee approval and written informed consent were obtained. Dual-echo, double inversion-recovery, high-resolution T1-weighted and diffusion-tensor (DT) MR was performed in 31 fatigued MSers, 32 non-fatigued MSers, and 35 control subjects. Global and regional atrophy and DT MR measures of damage to lesions, NAWM, and GM were compared (analysis of variance).

Results: Lesional, atrophy, and DT MR measures of global damage to brain, white matter (WM), and GM did not differ between fatigued and non-fatigued MSers. Compared with non-fatigued MSers and control subjects, fatigued MSers experienced atrophy of the right side of the accumbens (mean volume ± standard deviation, 0.37 mL ± 0.09 in control subjects; 0.39 mL ± 0.1 in non-fatigued MSers; and 0.33 mL ± 0.09 in fatigued MSers), right inferior temporal gyrus (ITG) (Montreal Neurological Institute [MNI] coordinates: 51, -51, -11; t value, 4.83), left superior frontal gyrus (MNI coordinates: -10, 49, 24; t value, 3.40), and forceps major (MNI coordinates: 11, -91, 18; t value, 3.37). They also had lower fractional anisotropy (FA) of forceps major (MNI coordinates: -17, -78, 6), left inferior fronto-occipital fasciculus (MNI coordinates: -25, 2, -11), and right anterior thalamic radiation (ATR) (MNI coordinates: 11, 2, -6) (P < .05, corrected). More lesions were found at T2-weighted imaging in fatigued MSers. Multivariable model was used to identify right ITG atrophy (odds ratio, 0.83; 95% confidence interval [CI]: 0.82, 0.97; P = .009) and right ATR FA (odds ratio, 0.74; 95% CI: 0.61, 0.90; P = .003) as covariates independently associated with fatigue (C statistic, 0.85). 

Conclusion: Damage to strategic brain WM and GM regions, in terms of microstructural abnormalities and atrophy, contributes to pathogenesis of fatigue in MS, whereas global lesional, WM, and GM damage does not seem to have a role.


  1. Did you really get stick for trying to define MS as dementia, Don Giovannoni ? Who gave you agro, bruv?

    But let’s be serious, how can anyone even attempt to argue that MS isn’t dementia? MS is a degenerative brain condition which, therefore, means that it is dementia. MS is, after all, “a chronic or persistent disorder of the mental processes caused by brain disease or injury,” which is exactly what dementia is classified as. MS is dementia whether you like it or not. The MS community seems to suffer from grandiose denials and arrogances, whereby they wish to separate themselves from extreme examples. They do not want to be bunched with a disease group that is associated with folks ‘losing their marbles’ or those ‘unsightly dudes in wheelchairs’. MSers want to be viewed as a more ‘hopeful’ group, which ultimately means a comprehensive avoidance of reality. This attitude will not help their cause in the long run.

    I suppose all this redefining of MS as dementia is part of your drive to get more sufferers onto expensive toxic medicines, no? That’s a shame, bredrin’, because there is no overwhelming evidence that crap like Campath-1H staves off progression. Relapses and progression are different beasts, Don Giovannoni. Controlling stuff on the outside of the brain is vastly different from regulating what’s happening inside. None of your current new drugs are, after all, any good at controlling progression.

    I propose a new strategy, Don Giovannoni. If you honestly believe that Lemtrada is the Holy Grail, I campaign that all those risking treatment that go on to develop progression should be financially compensated by Genzyme. After all, they’ve been misled into believing that Lemtrada is a potential cure and ought to be protected. All their future health needs and mobility provisions should be underwritten by Big Pharma. That is the only way to make this a fair deal for the tax payer and drug receiver.

    Put your money where your mouth is, my pharmaceutical friends. If you do not believe that Genzyme should be obliged to do this then avoid using the term “cure” when discussing the potential efficacy profile of new DMTs. Back me on this one, cuz.

    1. Interesting idea, however, if you were to make such a cash back promise maybe you would then want to further restrict who would have access to the drug. But it is not in the remit of pharma they want as many people to take the drug as possible, otherwise they would have done more to work out who responds to drugs and who does not. Failure of interferons and GA in (70% of) recipients gives a good example of the views of our pharma chums

      We already know that Lemtrada is not a panacea but look at 12 year follow-up data to get a feeling of the proportion of people converting to SPMS..don't kid does happen.
      However, I suspect that many people taking the risk of the drug may not be those who could gain maximal benefit and may start too late. Time will tell.

      However pharma paying money back for failure...I would say fat chance of that...just look at the UK Risk Sharing Scheme.

      The UK multiple sclerosis risk sharing scheme, was set up in 2002 after the National Institute for Health and Clinical Excellence (NICE) recommended against use of interferon beta and glatiramer acetate. Under the scheme patients were closely monitored to confirm the cost effectiveness of the drugs, with an agreement that prices would be reduced if patient outcomes were worse than predicted. The first report on the scheme in 2009 showed patient outcomes were much worse than predicted

      Have they coughed up yet?

    2. Big Pharma is corrupt. They ought to pay up for bad outcomes. Dr Dre is right!

    3. Dre you may be proved wrong; the 12 year data from Cambridge is looking very good, not to mention the brain atrophy data. I think you need to wait to see what happens before trying to predict the future. I am 8 year out since receiving my last course of campath and I am almost normal.

    4. Pay up for bad outcomes...i.e. drug does not work. Pharma does indeed pay millions for this failure...but not as compensation

    5. Dre is describing the risk-sharing scheme; this is what Bayer-Schering, Biogen-Idec, Merck-Serono and Teva signed up for. If the injectables did not deliver on their promise they were mean to lower the price of their drugs. Risk-sharing type schemes are common across Europe. I may highlight some of them in future posts.

  2. Before your dementia posts I was unaware of the possibility of cognitive impairment. It was not a happy realization. I'd rather know than not, so thank you.

  3. I could not access the survey, told I needed permission to do so.

  4. Dre always has a way to so effectively say what I'm thinking but can't quite say right. He should comment more often. He's a major asset to this blog, so much so that he ought to be featured as a regular contributor.

    1. Maybe he could fund some MS research with his new found wealth after selling out to apple:-)

    2. Beats B-cell depleting therapy by Dr. Dre.

    3. "I suspect Not holistic enough :-)"

      Beats bee sting therapy by Dr. Dre.


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