Thursday, 10 November 2011

Diffusion tensor imaging and cognition

Epub ahead of printYu et al. Multiple white matter tract abnormalities underlie cognitive impairment in RRMS. Neuroimage. 2011 Oct 29.

Diffusion tensor imaging (DTI) is a sensitive MRI technique for detecting structural tissue damage in the brain and spinal cord. 

In this study, the researchers investigated DTI abnormalities in individuals with RRMS and examined the relations between imaging-based measures of white matter injury and cognitive impairment. 

37 individuals with RRMS were compared to 20 healthy controls. 

Cognitive impairment was assessed with standard tests.

Correlations between DTI-metrics and cognition were explored in regions demonstrating significant differences between the RRMS patients and the control group. 

Lower DTI measurements were found in RRMS participants compared to controls across the tract skeleton (0.40±0.03 vs. 0.43±0.01, p<0.01). 

In the RRMS group, correlations were found between a reduction in DTI-metrics and cognitive impairment in cognitively-relevant white matter tracts.

These findings indicate the important role for DTI in delineating mechanisms underlying MS-associated cognitive impairment and suggest that DTI could play a critical role in monitoring the clinical and cognitive effects of MS.


Fig: DTI image showing white matter tracts in the brain.

"Is this result surprising? Damage to white matter tracts correlates with cognitive impairment. Best not to let the tracts become damaged in the first place; another argument for active treatment ASAP after disease onset. It is better to prevent damage than to try and repair it."

"This type of research not only increases our understanding of MS, but may allow us to monitor the disease more intelligently. DTI may be included as an outcome measure in future clinical trials."

6 comments:

  1. How likely is it that imaging techniques such as these will eventually make it into routine monitoring of MS patients to map disease progression and, therefore, help in making therapy decisions?

    ReplyDelete
  2. A totally unrelated subject (but can't find anywhere else on the blog to post), here is a follow-up on the pharma ethics discussions we had a couple of weeks ago.

    I would love to have Prof G's thoughts on this post:

    http://www.wheelchairkamikaze.com/2011/11/greed-trumps-common-sense-once-again.html

    ReplyDelete
  3. Re: "http://www.wheelchairkamikaze.com/2011/11/greed-trumps-common-sense-once-again.html"

    No surprise here; if your incentive for work is making money the Chiefs and Indians will maximise this. The pharma industry is no different to any other industry.

    There is also the IP sharing deal with Bioge-Idec re Rituximab and Ocrelizumab that you need to consider. Roche/Genentech and Biogen-Idec have a 50%:50% share with Rituximab and 75%:25% deal with Ocrelizumab.

    ReplyDelete
  4. This is the 3 Nov blog post from a Spanish neurologist neuroimmunology.wordpress.com/2011/11/03/rituximab-vs-ocrelizumab-in-multiple-sclerosis/
    He/she says:
    "We have then, a very good therapy, pretty safe and with a huge use experience, Rituximab. We have a very good therapy, not so safe or, at least, that raises serious concerns about some safety issues, some of them leading to patients’ deaths and that has not been used in clinical practice yet. What should we do?
    I think that if we, neurologists, have any trace of common sense, we should push for a phase III trial on Rituximab, convince Roche and Biogen of getting rid of Ocrelizumab (their losses can be still higher if they keep pushing that option) and persuade them that they have a nice therapy, that probably no other company will challenge on the short term and will give them profits for sure. In my opinion that is the best way of saving governments and companies money, accelerating the approval of a new therapy for aggressive MS and avoiding unknown risks. The alternative should be a public or privately funded (through foundations or patients’ associations) alternative trial to overcome the commercial criteria in drug development."

    What do you think of this opinion? I know that 'probably no other company will challenge on the short term' is already not true and Rituximab is already being challenged.

    I find it frightening that a drug abandoned as too dangerous for RA & lupus is being tested for MS. MSers may have 'higher risk tolerance' but they should not have to take something risky when a safer alternative was possible.
    www.reuters.com/article/2010/03/08/roche-idUSLDE62705720100308 says that most of the opportunistic infections in the RA & lupus trials were reported from Asia. I wonder if the ocrelizumab MS trials have patients in Asia or if they decided not to run the trials here (to make it appear safer).

    ReplyDelete
  5. This is the 3 Nov blog post from a Spanish neurologist neuroimmunology.wordpress.com/2011/11/03/rituximab-vs-ocrelizumab-in-multiple-sclerosis/
    He/she says:
    "We have then, a very good therapy, pretty safe and with a huge use experience, Rituximab. We have a very good therapy, not so safe or, at least, that raises serious concerns about some safety issues, some of them leading to patients’ deaths and that has not been used in clinical practice yet. What should we do?
    I think that if we, neurologists, have any trace of common sense, we should push for a phase III trial on Rituximab, convince Roche and Biogen of getting rid of Ocrelizumab (their losses can be still higher if they keep pushing that option) and persuade them that they have a nice therapy, that probably no other company will challenge on the short term and will give them profits for sure. In my opinion that is the best way of saving governments and companies money, accelerating the approval of a new therapy for aggressive MS and avoiding unknown risks. The alternative should be a public or privately funded (through foundations or patients’ associations) alternative trial to overcome the commercial criteria in drug development."

    What do you think of this opinion? I know that 'probably no other company will challenge on the short term' is already not true and Rituximab is already being challenged.

    I feel it's frightening that a drug abandoned as too dangerous for RA & lupus is being tested for MS. MSers may have 'higher risk tolerance' but they should not have to take something risky when a safer alternative was possible.
    www.reuters.com/article/2010/03/08/roche-idUSLDE62705720100308 says that most of the opportunistic infections in the RA & lupus trials were reported from Asia. So I wonder if the ocrelizumab MS trials have any patients in Asia or if they decided not to run the trials here (to make it appear safer).

    A few days ago you said "Rituximab is more likely to be destroyed folllowing injection as eventually the mouse aspects in the antibody will be recognised by the immune system. Therefore, ocrelizumab was developed, which is a more humanised antibody to avoid this ..."
    That Rituximab will be destroyed by the immune system - is this something expected to happen or has it actually been happening?

    ReplyDelete
  6. Re: "I feel it's frightening that a drug abandoned as too dangerous for RA & lupus is being tested for MS. MSers may have 'higher risk tolerance' but they should not have to take something risky when a safer alternative was possible."

    The decision of Roche to develop Ocrelizumab and not Rituximab is a complex one. A lot of neurologists, and Biogen-Idec, lobbied Genentech/Roche to go with Rituximab.

    We don't have the necessary information at hand to make a call on Ocrelizumab being more risky than Rituximab in MS. The deaths in the lupus and RA trials may be related to factors unique to those diseases. I do however agree that unless Roche put the necessary information into the public domain it looks as if their decision to go with ocrelizumab was driven by corporate strategy rather than patient safety.

    I am aware of a lobby in the US that is considering applying to the NIH for funds to launch a trial phase 3 trial of Rituximab in MS. So we may yet have the option of using Rituximab in MS.

    Regarding your point about MS'ers being higher risk takers may be correct. However, there have been several comparative that show rheumatologists are prepared to take greater risks than neurologists. As the gatekeepers to treatment this means rheumatology patients are more likely to be treated aggressively.

    ReplyDelete

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