Contributions
Abstract: P501
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
We previously reported an increase in cerebral ventricle volume (VV) prior to onset of clinical signs in the experimental autoimmune encephalomyelitis (EAE) model of MS. Here we extended these findings in EAE and investigated VV in MS patients.
We performed serial MRI scans in EAE mice to monitor longitudinal changes in VV during remission and relapse. SJL EAE mice were imaged every 2-3 days from d0 to d64 post-immunization, on a 9.4T animal MRI scanner. In MS patients, we investigated VV changes by analyzing MRI data that was acquired in a previous clinical study. Patients with definite MS (n=33) and at least one contrast-enhancing lesion (CEL) had each undergone a total of 13 MRI examinations over 1 year. A reference cohort of n=8 healthy individuals who had undergone multiple serial MRI scans over a period of several months served as controls. Absolute VV for mouse and human was quantified using FSL5.0 and corrected manually.
In mice we observed a robust increase in VV during the first disease peak, accompanied by CEL. Upon remission of clinical signs, VV of all mice returned to normal. Subsequent VV enlargements occurred in parallel to clinical exacerbations. We also observed fluctuations in the VV of MS patients, with substantial heterogeneity in the volatility of changes. The coefficient of variation in MS VV was significantly greater than that of controls. The range of VV changes in the control group was ±6% relative to baseline; 21/33 MS patients showed VV changes exceeding this threshold, and a majority of these showed VV contraction following expansion. Sequential VV measurements were analyzed as a time series and compared with CEL, T2- and black hole lesion volumes and counts. Half of the patients showed significant temporal relationships between VV fluctuations and changes in lesions (cross correlations between time series). Additional significant cross correlations with VV were seen for cognitive and motoric tests.
These results show that the dynamic VV changes during the course of disease in EAE may also occur in some MS patients. The fact that VV often contracted following expansion argues that these variations are not merely the result of brain atrophy due to neurodegeneration, but rather reflect some process related to the inflammatory status. The mechanisms underlying this phenomenon, and the potential prognostic and diagnostic value of VV as a contrast-free MRI parameter for MS patients, remain topics for further investigation.
Disclosure: JMM: has received presentation fees from Novartis.
LB: nothing to disclose
JBS: received speaking fees and travel grants from Bayer Healthcare, Sanofi-Aventis/Genzyme, Biogen and Teva Pharmaceuticals, unrelated to the present work.
FP: reports research grants and speaker honoraria from Bayer, Teva, Genzyme, Merck, Novartis, MedImmune and is member of the steering committee of the OCTIMS study (Novartis), all unrelated to the present work.
CID: nothing to disclose
TN: is founder and CEO of MRI.TOOLS GmbH, chair of the Highfield and Applications study group of the International Society of Magnetic Resonance in Medicine, and has received travel funds from Siemens Healthcare.
AP: nothing to disclose
SW: has received presentation fees from Novartis.
Abstract: P501
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
We previously reported an increase in cerebral ventricle volume (VV) prior to onset of clinical signs in the experimental autoimmune encephalomyelitis (EAE) model of MS. Here we extended these findings in EAE and investigated VV in MS patients.
We performed serial MRI scans in EAE mice to monitor longitudinal changes in VV during remission and relapse. SJL EAE mice were imaged every 2-3 days from d0 to d64 post-immunization, on a 9.4T animal MRI scanner. In MS patients, we investigated VV changes by analyzing MRI data that was acquired in a previous clinical study. Patients with definite MS (n=33) and at least one contrast-enhancing lesion (CEL) had each undergone a total of 13 MRI examinations over 1 year. A reference cohort of n=8 healthy individuals who had undergone multiple serial MRI scans over a period of several months served as controls. Absolute VV for mouse and human was quantified using FSL5.0 and corrected manually.
In mice we observed a robust increase in VV during the first disease peak, accompanied by CEL. Upon remission of clinical signs, VV of all mice returned to normal. Subsequent VV enlargements occurred in parallel to clinical exacerbations. We also observed fluctuations in the VV of MS patients, with substantial heterogeneity in the volatility of changes. The coefficient of variation in MS VV was significantly greater than that of controls. The range of VV changes in the control group was ±6% relative to baseline; 21/33 MS patients showed VV changes exceeding this threshold, and a majority of these showed VV contraction following expansion. Sequential VV measurements were analyzed as a time series and compared with CEL, T2- and black hole lesion volumes and counts. Half of the patients showed significant temporal relationships between VV fluctuations and changes in lesions (cross correlations between time series). Additional significant cross correlations with VV were seen for cognitive and motoric tests.
These results show that the dynamic VV changes during the course of disease in EAE may also occur in some MS patients. The fact that VV often contracted following expansion argues that these variations are not merely the result of brain atrophy due to neurodegeneration, but rather reflect some process related to the inflammatory status. The mechanisms underlying this phenomenon, and the potential prognostic and diagnostic value of VV as a contrast-free MRI parameter for MS patients, remain topics for further investigation.
Disclosure: JMM: has received presentation fees from Novartis.
LB: nothing to disclose
JBS: received speaking fees and travel grants from Bayer Healthcare, Sanofi-Aventis/Genzyme, Biogen and Teva Pharmaceuticals, unrelated to the present work.
FP: reports research grants and speaker honoraria from Bayer, Teva, Genzyme, Merck, Novartis, MedImmune and is member of the steering committee of the OCTIMS study (Novartis), all unrelated to the present work.
CID: nothing to disclose
TN: is founder and CEO of MRI.TOOLS GmbH, chair of the Highfield and Applications study group of the International Society of Magnetic Resonance in Medicine, and has received travel funds from Siemens Healthcare.
AP: nothing to disclose
SW: has received presentation fees from Novartis.