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June 04, 2013; 80 (23) Article

Brain metabolic changes suggestive of axonal damage in radiologically isolated syndrome

Maria Laura Stromillo, Antonio Giorgio, Francesca Rossi, Marco Battaglini, Bahia Hakiki, Gianmichele Malentacchi, Mario Santangelo, Claudio Gasperini, Maria Letizia Bartolozzi, Emilio Portaccio, Maria Pia Amato, Nicola De Stefano
First published May 1, 2013, DOI: https://doi.org/10.1212/WNL.0b013e318295d707
Maria Laura Stromillo
From the Department of Neurological and Behavioral Sciences (M.L.S., A.G., F.R., M.B., N.D.), University of Siena, Siena; Department of Neurology (B.H., E.P., M.P.A.), University of Florence, Florence; Neurology Unit (G.M.), Potenza Hospital, Potenza; Neurology Unit (M.S.), Carpi Hospital, Carpi; San Camillo-Forlanini Hospital (C.G.), Rome; and Neurology Unit (M.L.B.), Empoli Hospital, Empoli, Italy.
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Antonio Giorgio
From the Department of Neurological and Behavioral Sciences (M.L.S., A.G., F.R., M.B., N.D.), University of Siena, Siena; Department of Neurology (B.H., E.P., M.P.A.), University of Florence, Florence; Neurology Unit (G.M.), Potenza Hospital, Potenza; Neurology Unit (M.S.), Carpi Hospital, Carpi; San Camillo-Forlanini Hospital (C.G.), Rome; and Neurology Unit (M.L.B.), Empoli Hospital, Empoli, Italy.
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Francesca Rossi
From the Department of Neurological and Behavioral Sciences (M.L.S., A.G., F.R., M.B., N.D.), University of Siena, Siena; Department of Neurology (B.H., E.P., M.P.A.), University of Florence, Florence; Neurology Unit (G.M.), Potenza Hospital, Potenza; Neurology Unit (M.S.), Carpi Hospital, Carpi; San Camillo-Forlanini Hospital (C.G.), Rome; and Neurology Unit (M.L.B.), Empoli Hospital, Empoli, Italy.
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Marco Battaglini
From the Department of Neurological and Behavioral Sciences (M.L.S., A.G., F.R., M.B., N.D.), University of Siena, Siena; Department of Neurology (B.H., E.P., M.P.A.), University of Florence, Florence; Neurology Unit (G.M.), Potenza Hospital, Potenza; Neurology Unit (M.S.), Carpi Hospital, Carpi; San Camillo-Forlanini Hospital (C.G.), Rome; and Neurology Unit (M.L.B.), Empoli Hospital, Empoli, Italy.
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Bahia Hakiki
From the Department of Neurological and Behavioral Sciences (M.L.S., A.G., F.R., M.B., N.D.), University of Siena, Siena; Department of Neurology (B.H., E.P., M.P.A.), University of Florence, Florence; Neurology Unit (G.M.), Potenza Hospital, Potenza; Neurology Unit (M.S.), Carpi Hospital, Carpi; San Camillo-Forlanini Hospital (C.G.), Rome; and Neurology Unit (M.L.B.), Empoli Hospital, Empoli, Italy.
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Gianmichele Malentacchi
From the Department of Neurological and Behavioral Sciences (M.L.S., A.G., F.R., M.B., N.D.), University of Siena, Siena; Department of Neurology (B.H., E.P., M.P.A.), University of Florence, Florence; Neurology Unit (G.M.), Potenza Hospital, Potenza; Neurology Unit (M.S.), Carpi Hospital, Carpi; San Camillo-Forlanini Hospital (C.G.), Rome; and Neurology Unit (M.L.B.), Empoli Hospital, Empoli, Italy.
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Mario Santangelo
From the Department of Neurological and Behavioral Sciences (M.L.S., A.G., F.R., M.B., N.D.), University of Siena, Siena; Department of Neurology (B.H., E.P., M.P.A.), University of Florence, Florence; Neurology Unit (G.M.), Potenza Hospital, Potenza; Neurology Unit (M.S.), Carpi Hospital, Carpi; San Camillo-Forlanini Hospital (C.G.), Rome; and Neurology Unit (M.L.B.), Empoli Hospital, Empoli, Italy.
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Claudio Gasperini
From the Department of Neurological and Behavioral Sciences (M.L.S., A.G., F.R., M.B., N.D.), University of Siena, Siena; Department of Neurology (B.H., E.P., M.P.A.), University of Florence, Florence; Neurology Unit (G.M.), Potenza Hospital, Potenza; Neurology Unit (M.S.), Carpi Hospital, Carpi; San Camillo-Forlanini Hospital (C.G.), Rome; and Neurology Unit (M.L.B.), Empoli Hospital, Empoli, Italy.
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Maria Letizia Bartolozzi
From the Department of Neurological and Behavioral Sciences (M.L.S., A.G., F.R., M.B., N.D.), University of Siena, Siena; Department of Neurology (B.H., E.P., M.P.A.), University of Florence, Florence; Neurology Unit (G.M.), Potenza Hospital, Potenza; Neurology Unit (M.S.), Carpi Hospital, Carpi; San Camillo-Forlanini Hospital (C.G.), Rome; and Neurology Unit (M.L.B.), Empoli Hospital, Empoli, Italy.
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Emilio Portaccio
From the Department of Neurological and Behavioral Sciences (M.L.S., A.G., F.R., M.B., N.D.), University of Siena, Siena; Department of Neurology (B.H., E.P., M.P.A.), University of Florence, Florence; Neurology Unit (G.M.), Potenza Hospital, Potenza; Neurology Unit (M.S.), Carpi Hospital, Carpi; San Camillo-Forlanini Hospital (C.G.), Rome; and Neurology Unit (M.L.B.), Empoli Hospital, Empoli, Italy.
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Maria Pia Amato
From the Department of Neurological and Behavioral Sciences (M.L.S., A.G., F.R., M.B., N.D.), University of Siena, Siena; Department of Neurology (B.H., E.P., M.P.A.), University of Florence, Florence; Neurology Unit (G.M.), Potenza Hospital, Potenza; Neurology Unit (M.S.), Carpi Hospital, Carpi; San Camillo-Forlanini Hospital (C.G.), Rome; and Neurology Unit (M.L.B.), Empoli Hospital, Empoli, Italy.
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Nicola De Stefano
From the Department of Neurological and Behavioral Sciences (M.L.S., A.G., F.R., M.B., N.D.), University of Siena, Siena; Department of Neurology (B.H., E.P., M.P.A.), University of Florence, Florence; Neurology Unit (G.M.), Potenza Hospital, Potenza; Neurology Unit (M.S.), Carpi Hospital, Carpi; San Camillo-Forlanini Hospital (C.G.), Rome; and Neurology Unit (M.L.B.), Empoli Hospital, Empoli, Italy.
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Citation
Brain metabolic changes suggestive of axonal damage in radiologically isolated syndrome
Maria Laura Stromillo, Antonio Giorgio, Francesca Rossi, Marco Battaglini, Bahia Hakiki, Gianmichele Malentacchi, Mario Santangelo, Claudio Gasperini, Maria Letizia Bartolozzi, Emilio Portaccio, Maria Pia Amato, Nicola De Stefano
Neurology Jun 2013, 80 (23) 2090-2094; DOI: 10.1212/WNL.0b013e318295d707

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Abstract

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.

GLOSSARY

CB=
central brain;
CGM=
gray matter of the occipito-parietal cortex;
Cho=
choline;
Cr=
creatine;
DIT=
dissemination in time;
1H-MRSI=
proton magnetic resonance spectroscopic imaging;
HC=
healthy controls;
LL=
lesion load;
MR=
magnetic resonance;
MS=
multiple sclerosis;
NAA=
N-acetylaspartate;
NAWM=
normal-appearing white matter;
NBV=
normalized brain volume;
RIS=
radiologically isolated syndrome;
VOI=
volume of interest;
WM=
white matter

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 2084

  • Received October 29, 2012.
  • Accepted in final form February 12, 2013.
  • © 2013 American Academy of Neurology
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Disputes & Debates: Rapid online correspondence

  • Early metabolic effects in axonal damage
    • Heikki Savolainen, Prof., Dept. of Occup. Safety & Hlth., Tampere, Finlandheikki.savolainen@stm.fi
    Submitted June 13, 2013
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