Gray- and White-Matter Changes 1 Year after First Clinical Episode of Multiple Sclerosis: MR Imaging

Raz, Eytan; Cercignani, Mara; Sbardella, Emilia; Totaro, P.; Pozzilli, Carlo; Bozzali, Marco; Pantano, Patrizia

doi:10.1148/radiol.10100626

Cited by 75 publications

(81 citation statements)

References 45 publications

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“…22 No significant differences were found in whole-brain, global GM, WM, and/or cortical volumes between the 2 groups. This confirms the results of some recent studies that showed that selective regional, but not global, atrophy occurs from clinical onset to conversion to clinically definite MS. [17][18][19][20] This study provides strong evidence that regional GM atrophy is exclusively confined to the SDGM and not to cortical regions in the first 4 years of disease duration. Our findings suggest, therefore, that future studies should concentrate more on understanding the pathogenetic mechanisms leading to selective SDGM rather than to cortical GM damage in patients with early RRMS.…”

Section: Discussionmentioning

confidence: 59%

“…[5][6][7] More recently, research has focused on determining the extent of GM pathology at the first clinical event in patients presenting with CIS [8][9][10][11][12][13][14][15][16] or on its evolution with conversion to clinically definite MS. [17][18][19][20] It has been reported that global GM volume measures are not sensitive enough to detect GM atrophy at the time of the initial attack.…”

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confidence: 99%

“…11 Consequently, GM atrophy studies in patients with CIS have increasingly turned to regional segmentation techniques to identify specific structures with a stronger predilection for disease susceptibility and conversion to clinically definite MS. [8][9][10][11]13,14,16,17,19,21 The aim of this study was to investigate differences in the extent of SDGM and cortical atrophy in a large sample of patients with CIS and early RRMS. Another goal was to explore the relationship between SDGM and cortical atrophy and other MR imaging and clinical outcomes in these disease subtypes.…”

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confidence: 99%

“…[5][6][7] Other nonconventional MR imaging techniques have also contributed to determining the extent of GM damage in patients with MS. 2 The role of GM pathology in MS has come under increasingly close scrutiny, especially after it was shown that GM atrophy predicts clinical outcomes better than WM damage. [5][6][7] More recently, research has focused on determining the extent of GM pathology at the first clinical event in patients presenting with CIS [8][9][10][11][12][13][14][15][16] or on its evolution with conversion to clinically definite MS. [17][18][19][20] It has been reported that global GM volume measures are not sensitive enough to detect GM atrophy at the time of the initial attack. 11 Consequently, GM atrophy studies in patients with CIS have increasingly turned to regional segmentation techniques to identify specific structures with a stronger predilection for disease susceptibility and conversion to clinically definite MS. [8][9][10][11]13,14,16,17,19,21 The aim of this study was to investigate differences in the extent of SDGM and cortical atrophy in a large sample of patients with CIS and early RRMS.…”

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confidence: 99%

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Subcortical and Cortical Gray Matter Atrophy in a Large Sample of Patients with Clinically Isolated Syndrome and Early Relapsing-Remitting Multiple Sclerosis

Bergsland

Horáková²,

Dwyer

et al. 2012

AJNR Am J Neuroradiol

139

134

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BACKGROUND AND PURPOSE:Recent studies have shown that selective regional, but not global, GM atrophy occurs from clinical onset to conversion to clinically definite MS. Our aim was to investigate the difference in the extent of SDGM and cortical atrophy in a large sample of patients with CIS and early RRMS and to explore the relationship between SDGM and cortical atrophy and other MR imaging and clinical outcomes. MATERIALS AND METHODS:Two hundred twelve patients with CIS recruited at the first clinical event (mean age, 29.3 years; median EDSS, 1.5; median disease duration, 3 months) and 177 patients with early RRMS (mean age, 30.7 years; median EDSS, 2.0; median disease duration, 47 months) were imaged on a 1.5T scanner by using a high-resolution 3D T1 spoiled gradient-recalled sequence. Volumetric data for SDGM structures were obtained by using FSL FIRST, while whole-brain, GM, white matter, cortical, and lateral ventricle volumes were estimated by using SIENAX software. Comparisons between the groups were adjusted for age and sex. RESULTS:Patients with early RRMS showed significantly lower SDGM but not cortical volumes compared with patients with CIS. The most apparent SDGM differences were evident in the caudate and thalamus (P Ͻ .0001), total SDGM (P ϭ .0001), and globus pallidus (P ϭ .01). Patients with CIS with a median T2 lesion volume Ͼ4.49 mL showed lower total SDGM, caudate, thalamus (P Ͻ .001), globus pallidus (P ϭ .007), hippocampus (P ϭ .004), and putamen (P ϭ .01) volumes and higher lateral ventricle volume (P ϭ .001) than those with a median T2 lesion volume Ͻ4.49 mL. Decreased thalamic volume showed the most consistent relationship with MR imaging outcomes (P Ͻ .0001) in patients with CIS.CONCLUSIONS: Significant SDGM, but not cortical, atrophy develops during the first 4 years of the RRMS. GM atrophy is relevant for disease progression from the earliest clinical stages.ABBREVIATIONS: ASA ϭ Avonex-Steroid-Azathioprine; CIS ϭ clinically isolated syndrome; EDSS ϭ Expanded Disease Status Scale; FSL ϭ FMRIB Software Library; GM ϭ gray matter; NBV ϭ normalized brain volume; NCV ϭ normalized cortical volume; NGMV ϭ normalized gray matter volume; NLVV ϭ normalized lateral ventricle volume; NWMV ϭ normalized white matter volume; RRMS ϭ relapsing remitting MS; SDGM ϭ subcortical deep gray matter; SET ϭ Study of Early Interferon ␤ 1a Treatment in High Risk Subjects after CIS M R imaging is a vital tool enabling clinicians to diagnose, monitor, and predict the progression of MS. Conventional MR imaging has proved to be very sensitive for detecting focal changes in the WM, yet it is relatively insensitive to involvement of the GM in MS. GM pathology in MS is quite different from that in WM, with only mild blood-brain barrier disruption and little-to-no inflammation due to minimal Tcell infiltration.1 Hence, the difference between lesion and normal GM relaxation times on MR imaging is less than that seen between lesion and normal white matter. 2In the past decade, continuous effort has been made to develop n...

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Section: Discussionmentioning

confidence: 59%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Subcortical and Cortical Gray Matter Atrophy in a Large Sample of Patients with Clinically Isolated Syndrome and Early Relapsing-Remitting Multiple Sclerosis

Bergsland

Horáková²,

Dwyer

et al. 2012

AJNR Am J Neuroradiol

139

134

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“…Indeed, VBM has been used extensively in the analysis of brain atrophy in MS (Battaglini et al., 2009; Bendfeldt et al., 2009, 2010; Ceccarelli et al., 2008; Raz et al., 2010). We have used VBM to demonstrate that there were distinct associations between voxelwise GM loss and specific clinical disabilities (MacKenzie‐Graham et al., 2016).…”

Section: Introductionmentioning

confidence: 99%

Estriol‐mediated neuroprotection in multiple sclerosis localized by voxel‐based morphometry

et al. 2018

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IntroductionProgressive gray matter (GM) atrophy is a hallmark of multiple sclerosis (MS). Cognitive impairment has been observed in 40%–70% of MS patients and has been linked to GM atrophy. In a phase 2 trial of estriol treatment in women with relapsing–remitting MS (RRMS), higher estriol levels correlated with greater improvement on the paced auditory serial addition test (PASAT) and imaging revealed sparing of localized GM in estriol‐treated compared to placebo‐treated patients. To better understand the significance of this GM sparing, the current study explored the relationships between the GM sparing and traditional MRI measures and clinical outcomes.MethodsSixty‐two estriol‐ and forty‐nine placebo‐treated RRMS patients underwent clinical evaluations and brain MRI. Voxel‐based morphometry (VBM) was used to evaluate voxelwise GM sparing from high‐resolution T1‐weighted scans.ResultsA region of treatment‐induced sparing (TIS) was defined as the areas where GM was spared in estriol‐ as compared to placebo‐treated groups, localized primarily within the frontal and parietal cortices. We observed that TIS volume was directly correlated with improvement on the PASAT. Next, a longitudinal cognitive disability‐specific atlas (DSA) was defined by correlating voxelwise GM volumes with PASAT scores, that is, areas where less GM correlated with less improvement in PASAT scores. Finally, overlap between the TIS and the longitudinal cognitive DSA revealed a specific region of cortical GM that was preserved in estriol‐treated subjects that was associated with better performance on the PASAT.ConclusionsDiscovery of this region of overlap was biology driven, not based on an a priori structure of interest. It included the medial frontal cortex, an area previously implicated in problem solving and attention. These findings indicate that localized GM sparing during estriol treatment was associated with improvement in cognitive testing, suggesting a clinically relevant, disability‐specific biomarker for clinical trials of candidate neuroprotective treatments in MS.

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Disability-Specific Atlases of Gray Matter Loss in Relapsing-Remitting Multiple Sclerosis

et al. 2016

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IMPORTANCE Multiple sclerosis (MS) is characterized by progressive gray matter atrophy that strongly correlates with clinical disability, however it is not known if localized gray matter atrophy correlates with specific disabilities in MS patients. OBJECTIVE Our objective in this study was to understand the relationship between localized gray matter atrophy and clinical disability in a biology-driven, as opposed to a hypothesis-driven, manner. DESIGN, SETTING, AND PARTICIPANTS Magnetic resonance images were acquired from 133 female subjects with relapsing-remitting MS and analyzed using voxel-based morphometry (VBM) as well as volumetry. A regression analysis was then used to determine if voxelwise gray matter atrophy was associated with specific clinical deficits. MAIN OUTCOME AND MEASURES Voxelwise correlation of gray matter change with clinical outcome measures. RESULTS Worse performance on the multiple sclerosis functional composite correlated with voxelwise gray matter volume loss in the middle cingulate cortex and a cluster in the precentral gyrus bilaterally. In addition, worse performance on the Paced Auditory Serial Addition Test correlated with volume loss in the auditory and premotor cortex, while worse performance on the 9-hole peg test correlated with gray matter volume loss in Brodmann area 44 (Broca’s area). Finally, voxelwise gray matter loss in the right paracentral lobulus correlated with bowel and bladder disability. Thus, deficits in specific clinical tests were directly related to localized gray matter loss in clinically eloquent locations. CONCLUSIONS AND RELEVANCE These biology-driven data indicate that specific disabilities in MS are associated with voxelwise gray matter loss in distinct locations. This approach may be used to develop disability-specific biomarkers for use in future clinical trials of neuroprotective treatments in MS.

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Gray- and White-Matter Changes 1 Year after First Clinical Episode of Multiple Sclerosis: MR Imaging

Cited by 75 publications

References 45 publications

Subcortical and Cortical Gray Matter Atrophy in a Large Sample of Patients with Clinically Isolated Syndrome and Early Relapsing-Remitting Multiple Sclerosis

Subcortical and Cortical Gray Matter Atrophy in a Large Sample of Patients with Clinically Isolated Syndrome and Early Relapsing-Remitting Multiple Sclerosis

Estriol‐mediated neuroprotection in multiple sclerosis localized by voxel‐based morphometry

Disability-Specific Atlases of Gray Matter Loss in Relapsing-Remitting Multiple Sclerosis

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