The predictive value of gray matter atrophy in clinically isolated syndromes

Multiple Sclerosis Centre of Veneto Region, First Neurology Clinic, Department of Neurosciences, University Hospital of Padova, Via Giustiniani 5, 35128 Padova, Italy.
Neurology (Impact Factor: 8.29). 05/2011; 77(3):257-63. DOI: 10.1212/WNL.0b013e318220abd4
Source: PubMed


Although gray matter (GM) atrophy is recognized as a common feature of multiple sclerosis (MS), conflicting results have been obtained in patients with clinically isolated syndromes (CIS). Methodologic and clinical constraints may take account for literature discrepancies.
A total of 105 patients presenting with CIS and 42 normal controls (NC) were studied. At baseline, 65/105 patients with CIS met the criterion of dissemination in space of lesions (DIS+). All patients were clinically assessed by means of the Expanded Disability Status Scale every 6 months and underwent MRI evaluation at study entry and then annually for 4 years. Global and regional cortical thickness and deep GM atrophy were assessed using Freesurfer.
No significant reduction in GM atrophy was observed between the entire CIS group and the NC, excepting for the cerebellum cortical volume. When the 59 patients with CIS (46 DIS+, 13 DIS-) who converted to MS during the follow-up were compared to the NC, a significant atrophy in the precentral gyrus, superior frontal gyrus, thalamus, and putamen was observed (p ranging from 0.05 to 0.001). The multivariate analysis identified the atrophy of superior frontal gyrus, thalamus, and cerebellum as independent predictors of conversion to MS. CIS with atrophy of such areas had a double risk of conversion compared to DIS+ (odds ratio 9.6 vs 5.0).
Selective GM atrophy is relevant in patients with CIS who convert early to MS. The inclusion of GM analysis in the MS diagnostic workup is worthy of further investigation.

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    • "Therefore, the normal appearing WM (NAWM) pathology did not strictly parallel the level of disconnection within networks in our study. As neither regional macroscopic lesions nor regional NAWM damage fully explained resting state connectivity changes, the functional disconnection in associative networks could be related to GM pathology, which has already been proposed to act on cognitive dysfunction (Amato et al., 2007; Calabrese et al., 2011; Morgen et al., 2006). "
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    • "Determination of CL number and CL volume on DIR images and of volume of T2 WM lesions (T2WMLV) on FLAIR images was achieved by consensus of two experienced observers blind to patient identity and to the date of image acquisition, as previously described in detail (Calabrese et al., 2010) and in agreement with the recent MAGNIMS Study Group's recommendations (Geurts et al., 2011). Global and regional cortical thickness (CTh) (mean of right and left hemispheres) was performed on the volumetric FFE data sets by means of Freesurfer image analysis suite, as described in detail elsewhere (Calabrese et al., 2011). Spinal cord MRI included T1, T2, STIR and contrast enhancing T1 sequences. "
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    • "Some imaging studies suggest gray rather than white matter changes occur early, and predict the development of MS but other imaging studies are in conflict [2], [4]. "
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    ABSTRACT: The cause of multiple sclerosis (MS), its driving pathogenesis at the earliest stages, and what factors allow the first clinical attack to manifest remain unknown. Some imaging studies suggest gray rather than white matter may be involved early, and some postulate this may be predictive of developing MS. Other imaging studies are in conflict. To determine if there was objective molecular evidence of gray matter involvement in early MS we used high-resolution mass spectrometry to identify proteins in the cerebrospinal fluid (CSF) of first-attack MS patients (two independent groups) compared to established relapsing remitting (RR) MS and controls. We found that the CSF proteins in first-attack patients were differentially enriched for gray matter components (axon, neuron, synapse). Myelin components did not distinguish these groups. The results support that gray matter dysfunction is involved early in MS, and also may be integral for the initial clinical presentation.
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