Contributions
Abstract: P1097
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Neurodegeneration
Background: The critical role and location of the thalamus exposes this structure to different pathobiological processes in multiple sclerosis (MS) patients: Wallerian degeneration secondary to its extensive cortical and subcortical white matter (WM) connections and neuroinflammation due to cerebrospinal fluid (CSF) mediated immune cytotoxic factors. We investigated the contribution of different pathogenetic mechanisms to thalamic damage in patients at the earliest stages of MS.
Methods: Using a 3T scanner, dual-echo and 3DT1-weighted images were acquired from 70 pediatric MS patients and 26 age and sex-matched healthy controls (HC). To assess thalamic shape differences a vertex-analysis was performed using the FMRIB Integrated Registration and Segmentation Tool (FIRST). Cortical surface reconstruction and mean cortical thickness measurement were performed using FreeSurfer. Correlations between volumetric abnormalities vs clinical and conventional MRI variables were explored.
Results: Global thalamic volume did not differ between HC and pediatric MS patients (p=0.06). Thinning of several cortical regions was found in pediatric MS patients vs HC (p< 0.001). The vertex analysis revealed significant differences in thalamic shape between patients and HC with a prominent inwards displacement of thalamic ependymal surface and a relative sparing of ventrolateral thalamic surface (p< 0.05). No correlation was found between thalamic surface inwards displacement and WM lesion volumes, disease duration and clinical disability. Significant correlation was found between left hemisphere cortical thinning and surface inward displacement of the left medial pulvinar (p< 0.05).
Conclusions: In pediatric MS patients, the absence of correlations between thalamic volumetric abnormalities, focal WM lesions and clinical variables supports the hypothesis of an early damage, linked to acute inflammatory processes occurring close to disease onset rather than to Wallerian degeneration. The correlation existing between thalamic inward displacement and cortical thinning suggests a shared mechanism of damage likely linked to CSF immune cytotoxic factors.
Funding: Partially supported by Italian Ministry of Health (GR-2009-1529671) and Fondazione Italiana Sclerosi Multipla (FISM-2016-R-23).
Disclosure: E. De Meo, L. Moiola, P. Veggiotti, and A. Falini have nothing to disclose.
A. Ghezzi received honoraria for speaking from Biogen-Idec, Merck-Serono, Novartis, Genzyme, Teva, and Allergan, and for consultancy from Merck-Serono, Teva, Novartis, and Biogen-Idec; and received support for participation in national and international congresses from Schering, Biogen-Idec, Merck-Serono, Novartis, Genzyme, and Teva.
R. Capra received consulting fees from Novartis and Biogen and lecture fees and/or travel grants from Novartis, Biogen, Genzyme, and Sanofi-Aventis.
G. Comi has received consulting fees for participating on advisory boards from Novartis, Teva Pharmaceutical Ind. Ltd, Sanofi, Genzyme, Merck Serono, Bayer, Actelion and honorarium for speaking activities for Novartis, Teva Pharmaceutical Ind. Ltd, Sanofi, Genzyme, Merck Serono, Bayer, Biogen, ExceMED.
M. Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).
M.A. Rocca received speakers honoraria from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono, and Roche and receives research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla.
Abstract: P1097
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Neurodegeneration
Background: The critical role and location of the thalamus exposes this structure to different pathobiological processes in multiple sclerosis (MS) patients: Wallerian degeneration secondary to its extensive cortical and subcortical white matter (WM) connections and neuroinflammation due to cerebrospinal fluid (CSF) mediated immune cytotoxic factors. We investigated the contribution of different pathogenetic mechanisms to thalamic damage in patients at the earliest stages of MS.
Methods: Using a 3T scanner, dual-echo and 3DT1-weighted images were acquired from 70 pediatric MS patients and 26 age and sex-matched healthy controls (HC). To assess thalamic shape differences a vertex-analysis was performed using the FMRIB Integrated Registration and Segmentation Tool (FIRST). Cortical surface reconstruction and mean cortical thickness measurement were performed using FreeSurfer. Correlations between volumetric abnormalities vs clinical and conventional MRI variables were explored.
Results: Global thalamic volume did not differ between HC and pediatric MS patients (p=0.06). Thinning of several cortical regions was found in pediatric MS patients vs HC (p< 0.001). The vertex analysis revealed significant differences in thalamic shape between patients and HC with a prominent inwards displacement of thalamic ependymal surface and a relative sparing of ventrolateral thalamic surface (p< 0.05). No correlation was found between thalamic surface inwards displacement and WM lesion volumes, disease duration and clinical disability. Significant correlation was found between left hemisphere cortical thinning and surface inward displacement of the left medial pulvinar (p< 0.05).
Conclusions: In pediatric MS patients, the absence of correlations between thalamic volumetric abnormalities, focal WM lesions and clinical variables supports the hypothesis of an early damage, linked to acute inflammatory processes occurring close to disease onset rather than to Wallerian degeneration. The correlation existing between thalamic inward displacement and cortical thinning suggests a shared mechanism of damage likely linked to CSF immune cytotoxic factors.
Funding: Partially supported by Italian Ministry of Health (GR-2009-1529671) and Fondazione Italiana Sclerosi Multipla (FISM-2016-R-23).
Disclosure: E. De Meo, L. Moiola, P. Veggiotti, and A. Falini have nothing to disclose.
A. Ghezzi received honoraria for speaking from Biogen-Idec, Merck-Serono, Novartis, Genzyme, Teva, and Allergan, and for consultancy from Merck-Serono, Teva, Novartis, and Biogen-Idec; and received support for participation in national and international congresses from Schering, Biogen-Idec, Merck-Serono, Novartis, Genzyme, and Teva.
R. Capra received consulting fees from Novartis and Biogen and lecture fees and/or travel grants from Novartis, Biogen, Genzyme, and Sanofi-Aventis.
G. Comi has received consulting fees for participating on advisory boards from Novartis, Teva Pharmaceutical Ind. Ltd, Sanofi, Genzyme, Merck Serono, Bayer, Actelion and honorarium for speaking activities for Novartis, Teva Pharmaceutical Ind. Ltd, Sanofi, Genzyme, Merck Serono, Bayer, Biogen, ExceMED.
M. Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).
M.A. Rocca received speakers honoraria from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono, and Roche and receives research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla.