Nerve Damage can occur Early.


Stromillo ML, Giorgio A, Rossi F, Battaglini M, Hakiki B,
Malentacchi G, Santangelo M, Gasperini C, Bartolozzi ML, Portaccio E,
Amato MP, De Stefano N.
Brain metabolic changes suggestive of axonal damage in radiologically isolated syndrome.
Neurology. 2013 May. [Epub ahead of print]

BACKGROUND: The MRI incidental finding in asymptomatic subjects of brain white matter (WM) changes meeting the Barkhof criteria for the diagnosis of multiple sclerosis (MS) has been recently characterized as the radiologically isolated syndrome (RIS). This entity needs to be more specifically defined to allow risk stratification of these subjects. We used brain proton magnetic resonance spectroscopic imaging (1H-MRSI) to assess metabolic changes in an RIS population.
METHODS: Twenty-three RIS subjects who were classified according to the Okuda Criteria underwent 1H-MRSI examination with a central brain (CB) volume of interest (VOI) to measure levels of N-acetylaspartate (NAA) and choline (Cho) normalized to creatine (Cr) in the whole CB-VOI, in lesional/perilesional and normal-appearing WM regions, and in the cortical gray matter (CGM). The 1H-MRSI data were compared with those of 20 demographically matched healthy controls (HC).
RESULTS: NAA/Cr levels were significantly lower in RIS than in HC in all regions (p < 0.005 for all). No differences in Cho/Cr levels were found in either brain region. A single-subject analysis showed that NAA/Cr levels were at least 2 SDs below the HC mean in the 44% of RIS in the normal-appearing WM and in the 61% of RIS in the CGM.
CONCLUSION: Decreased brain NAA/Cr levels in a group of RIS subjects indicates that brain metabolic abnormalities suggestive of axonal damage can be significant even at this early disease stage. This information could be useful for stratifying RIS individuals with a high risk of progression to MS

 Radiologically isolated syndrome is when someone has a scan and lesions suggestive of MS are found before any clinical indication is found and by applying The Barkoff Criteria to use MRI in the aid of diagnosis of MS, at risk individuals can be found. This study at this early stage there is evidence of  nerve damage as assessed by loss of NAA. So the same as CIS and early MS there is nerve damage occurring from the get go, we need to get moving and treat early. The regulators and NICE need to wake up and give neuros tools to deal with this.

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  • Mousedoctor,

    Have there been any studies looking for spectroscopic changes during dmt treatment?


    • Does, for instance NAA show any improvement with any dmts, or does the NAA stay low, suggesting loss of neurons/loss of their integrity? Is there any decrease in the likes of glutamate with treatment? I would have surmised that the latter may be more amenable to change than the NAA. Improvement in NAA if it were to happen would seem like a very good sign.


      (Sorry for the anonymous posting, just don't feel I have an option)

    • I was leaving this for prof G to answer.

      Whilst NAA is concentrated in nerves and so a reduction was thought to be due to nerve loss it is now realised that NAA levels are at least partially reversible and this may be helped with DMT

      As for glutamate the source and site of action will be important factors

    • Interesting, thanks. Would be good if there was evidence that this could be used to monitor therapy response in individual patients.

  • Back in 2009 I had what is beleived to be Acute Disseminated Encephalomeylits (ADEM), but when I went into the hospital my MRI was normal.

    It appears this can happen in ADEM.

    Since that time, I have had yearly MRI's which were normal but I was having relapses. Last January I had a bad relapse and my MRI showed a new lesion and I started a DMT.

    My question is how does this fit into the Barkhof MRI criteria for dissemination in space, or is it that if a new lesion is detected this ovverides this criteria?


  • What is "brain proton magnetic resonance spectroscopic imaging (1H-MRSI)"?
    Is it used only for research?

    Are these "NAA/Cr measures" used outside research, to monitor damage in MSers?



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