Contributions
Abstract: P396
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Inflammation and tissue damage
Background: Lesional and atrophy data support the evidence of grey matter (GM) involvement in patients with clinically isolated syndrome (CIS) suggestive of MS. The hippocampus is affected early in MS, with characteristic subregional patterns of involvement at different stages of the disease. The subgranular layer of the dentate gyrus (DG) supports neurogenesis and there is evidence of its in-vivo expansion in relapsing-remitting (RR) MS patients.
Aims: To evaluate short-term patterns of regional hippocampal volume variations in CIS patients early in the course of the disease.
Methods: Brain dual-echo and 3D T1-weighted scans were acquired from 20 CIS patients within 2 months from clinical onset and after 3 months. Ten healthy controls (HC) were also studied. Manual hippocampal segmentation was performed according to a standardized procedure, and global volumes were derived. Radial atrophy distribution was assessed using 3D parametric surface mesh models.
Results: At baseline, CIS patients had a reduced radial distance (RD) (p< 0.05) involving the lateral CA1 subfield of both the right and left hippocampal tail and of the right hippocampal head. In the right hippocampus, RD was negatively correlated with T2, T1 and GD-lesion load (LL) (p< 0.05, R>-0.5). At 3 months, an expansion of the right hippocampus DG subfield was observed (p< 0.01), associated with homolateral CA1 and subiculum volume loss in the tail (p< 0.01) and a partial volume recovery in the head. Interestingly, in the left hippocampal tail, only a CA1 RD increase was found, with no DG expansion. Considering the radial variation between the timepoints in the right hippocampus, a volume increase in DG and a volume loss in CA1 region emerged. DG increase correlated positively with baseline T2, T1 and GD LL (p< 0.05) (R>0.5).
Conclusions: Regional hippocampal volume abnormalities occur in CIS patients, with higher susceptibility to damage of CA1 and subiculum. After an acute inflammatory event, hippocampal volume abnormalities are dynamic and modulated by the burden of inflammation, as suggested by the correlation between DG expansion and lesional measures. The lateralization of our data, predominantly in the right side, might be explained by an higher vulnerability to damage of this hemisphere. These is in agreement with previous works reporting a more marked volume loss of the right hippocampus with aging and in MS patients.
Disclosure: Drs Cacciaguerra, Pagani, Dackovic, and Stosic-Opincal have nothing to disclose.
Dr Mesaros has received funding for travelling and honoraria for speaking from Merck Serono, Novartis, Bayer Schering, Medis.
Dr Drulovic has served on scientific advisory boards for Merck Serono, Novartis, and Bayer Schering; has received funding for travelling and honoraria for speaking from Merck Serono, Teva, Novartis, Bayer Schering, Medis. She is the principal investigator in clinical trials for Merck Serono, Teva, Biogen Idec, Roche, Genzyme, a Sanofi Company, Receptos.
Prof. Filippi is Editor-in-Chief of the Journal of Neurology; serves on scientific advisory boards for Teva Pharmaceutical Industries; has received compensation for consulting services and/or speaking activities from Biogen Idec, Excemed, Novartis, and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Teva Pharmaceutical Industries, Novartis, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, Cure PSP, Alzheimer´s Drug Discovery Foundation (ADDF), the Jacques and Gloria Gossweiler Foundation (Switzerland), and ARiSLA (Fondazione Italiana di Ricerca per la SLA).
Dr Rocca received speakers honoraria from Biogen Idec, Novartis and ExceMed and receives research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla.
Abstract: P396
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Inflammation and tissue damage
Background: Lesional and atrophy data support the evidence of grey matter (GM) involvement in patients with clinically isolated syndrome (CIS) suggestive of MS. The hippocampus is affected early in MS, with characteristic subregional patterns of involvement at different stages of the disease. The subgranular layer of the dentate gyrus (DG) supports neurogenesis and there is evidence of its in-vivo expansion in relapsing-remitting (RR) MS patients.
Aims: To evaluate short-term patterns of regional hippocampal volume variations in CIS patients early in the course of the disease.
Methods: Brain dual-echo and 3D T1-weighted scans were acquired from 20 CIS patients within 2 months from clinical onset and after 3 months. Ten healthy controls (HC) were also studied. Manual hippocampal segmentation was performed according to a standardized procedure, and global volumes were derived. Radial atrophy distribution was assessed using 3D parametric surface mesh models.
Results: At baseline, CIS patients had a reduced radial distance (RD) (p< 0.05) involving the lateral CA1 subfield of both the right and left hippocampal tail and of the right hippocampal head. In the right hippocampus, RD was negatively correlated with T2, T1 and GD-lesion load (LL) (p< 0.05, R>-0.5). At 3 months, an expansion of the right hippocampus DG subfield was observed (p< 0.01), associated with homolateral CA1 and subiculum volume loss in the tail (p< 0.01) and a partial volume recovery in the head. Interestingly, in the left hippocampal tail, only a CA1 RD increase was found, with no DG expansion. Considering the radial variation between the timepoints in the right hippocampus, a volume increase in DG and a volume loss in CA1 region emerged. DG increase correlated positively with baseline T2, T1 and GD LL (p< 0.05) (R>0.5).
Conclusions: Regional hippocampal volume abnormalities occur in CIS patients, with higher susceptibility to damage of CA1 and subiculum. After an acute inflammatory event, hippocampal volume abnormalities are dynamic and modulated by the burden of inflammation, as suggested by the correlation between DG expansion and lesional measures. The lateralization of our data, predominantly in the right side, might be explained by an higher vulnerability to damage of this hemisphere. These is in agreement with previous works reporting a more marked volume loss of the right hippocampus with aging and in MS patients.
Disclosure: Drs Cacciaguerra, Pagani, Dackovic, and Stosic-Opincal have nothing to disclose.
Dr Mesaros has received funding for travelling and honoraria for speaking from Merck Serono, Novartis, Bayer Schering, Medis.
Dr Drulovic has served on scientific advisory boards for Merck Serono, Novartis, and Bayer Schering; has received funding for travelling and honoraria for speaking from Merck Serono, Teva, Novartis, Bayer Schering, Medis. She is the principal investigator in clinical trials for Merck Serono, Teva, Biogen Idec, Roche, Genzyme, a Sanofi Company, Receptos.
Prof. Filippi is Editor-in-Chief of the Journal of Neurology; serves on scientific advisory boards for Teva Pharmaceutical Industries; has received compensation for consulting services and/or speaking activities from Biogen Idec, Excemed, Novartis, and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Teva Pharmaceutical Industries, Novartis, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, Cure PSP, Alzheimer´s Drug Discovery Foundation (ADDF), the Jacques and Gloria Gossweiler Foundation (Switzerland), and ARiSLA (Fondazione Italiana di Ricerca per la SLA).
Dr Rocca received speakers honoraria from Biogen Idec, Novartis and ExceMed and receives research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla.