Contributions
Abstract: P468
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Normal appearing white matter (NAWM) damage is not randomly distributed though the brain in multiple sclerosis (MS), but it is more severe around the lateral ventricles. Indeed, an outside-in gradient in NAWM damage from periventricular NAWM toward deep grey matter has been observed across all the MS spectrum, possibly due to a proximity effect to CSF.
Objectives: To evaluate if in subjects with clinically isolated syndrome (CIS) the periventricular distribution of NAWM damage was associated with the presence of cerebrospinal fluid (CSF) oligoclonal bands (OCB).
Methods: Thirty subjects with a diagnosis of CIS (18 females, 12 males; mean age, 39 ± 11.8 years; EDSS range 0-2) were included in this study and underwent a brain MRI scan and CSF examination within 75 days from their first clinical event. The presence of CSF and serum oligoclonal bands was assessed for all CIS subjects. Twenty-four healthy volunteers (11 females, 13 males; mean age, 37.71 ± 19.5 years) were also recruited as MRI controls. Diffusion weighted MR was acquired for all subjects and used to compute skeletonized mean diffusivity (MD) NAWM maps. The supra-tentorial voxels between 2 and 6 mm of distance from the lateral ventricles were included in the periventricular NAWM mask while the voxels between 6 and 10 mm from the lateral ventricles were included in the deep NAWM mask; mean MD values were then computed separately for these two masks. Using healthy controls data to convert NAWM MD values in z scores, the NAWM damage gradient was calculated as (periventricular NAWM z score - deep NAWM z score) / (periventricular NAWM z score) and then compared between subjects with and without CSF OCB.
Results: Twenty CIS subjects presented with CSF-only OCB (CSF-OCB+), nine CIS with no OCB in CSF (CSF-OCB-) or serum and one with OCB in both serum and CSF. There was a significant steeper gradient of periventricular NAWM damage in with CSF-OCB+ CIS than in CSF-OCB- CIS subjects (0.35 ±0.05 vs. 0.26±0.05, t=4.45, p< 0.001). This difference in the NAMW periventricular gradient remained significant correcting for total WM lesion load and for brain parenchymal fraction (p=0.008). There was no difference in the two groups in total skeletonized MD (p=0.35).
Discussion: The association between presence of CSF-OCB and of a steeper outside-in gradient in NAWM periventricular damage supports a role for CSF soluble factors in mediating the distribution of NAWM damage in MS.
Disclosure: M. Pardini: receives research support from Novartis and reports personal fees from Merck Serono and Teva.
L.Gualco: no disclosures
G. Bommarito: no disclosures
L. Roccatagliata: no disclosures
A. Laroni: speaking honoraria from Biogen and Novartis
C. Solaro: served as a member of the advisory board of the following companies: Biogen Idec and Merck Serono; received speaking honoraria from Bayer Schering, Biogen Idec, Merck Serono, Teva, Almirall, and Sanofi Genzyme and research grants and support by the FISM (Fondazione Italiana Sclerosi Multipla)
A.Uccelli: has received consulting honoraria and/or speaker fees and basic science study grants from Biogen Idec; consulting honoraria and/or speaker fees from Genzyme, Roche, Sanofi Aventis, and Teva; consulting honoraria and/or speaker fees and a basic science study grant from Novartis; consulting honoraria and/or speaker fees and a basic science study grant from Merck Serono
E. Capello: no disclosures
M. Inglese: has received research grants from the NIH, NMSS, Novartis Pharmaceuticals, and Teva Neuroscience
Abstract: P468
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Normal appearing white matter (NAWM) damage is not randomly distributed though the brain in multiple sclerosis (MS), but it is more severe around the lateral ventricles. Indeed, an outside-in gradient in NAWM damage from periventricular NAWM toward deep grey matter has been observed across all the MS spectrum, possibly due to a proximity effect to CSF.
Objectives: To evaluate if in subjects with clinically isolated syndrome (CIS) the periventricular distribution of NAWM damage was associated with the presence of cerebrospinal fluid (CSF) oligoclonal bands (OCB).
Methods: Thirty subjects with a diagnosis of CIS (18 females, 12 males; mean age, 39 ± 11.8 years; EDSS range 0-2) were included in this study and underwent a brain MRI scan and CSF examination within 75 days from their first clinical event. The presence of CSF and serum oligoclonal bands was assessed for all CIS subjects. Twenty-four healthy volunteers (11 females, 13 males; mean age, 37.71 ± 19.5 years) were also recruited as MRI controls. Diffusion weighted MR was acquired for all subjects and used to compute skeletonized mean diffusivity (MD) NAWM maps. The supra-tentorial voxels between 2 and 6 mm of distance from the lateral ventricles were included in the periventricular NAWM mask while the voxels between 6 and 10 mm from the lateral ventricles were included in the deep NAWM mask; mean MD values were then computed separately for these two masks. Using healthy controls data to convert NAWM MD values in z scores, the NAWM damage gradient was calculated as (periventricular NAWM z score - deep NAWM z score) / (periventricular NAWM z score) and then compared between subjects with and without CSF OCB.
Results: Twenty CIS subjects presented with CSF-only OCB (CSF-OCB+), nine CIS with no OCB in CSF (CSF-OCB-) or serum and one with OCB in both serum and CSF. There was a significant steeper gradient of periventricular NAWM damage in with CSF-OCB+ CIS than in CSF-OCB- CIS subjects (0.35 ±0.05 vs. 0.26±0.05, t=4.45, p< 0.001). This difference in the NAMW periventricular gradient remained significant correcting for total WM lesion load and for brain parenchymal fraction (p=0.008). There was no difference in the two groups in total skeletonized MD (p=0.35).
Discussion: The association between presence of CSF-OCB and of a steeper outside-in gradient in NAWM periventricular damage supports a role for CSF soluble factors in mediating the distribution of NAWM damage in MS.
Disclosure: M. Pardini: receives research support from Novartis and reports personal fees from Merck Serono and Teva.
L.Gualco: no disclosures
G. Bommarito: no disclosures
L. Roccatagliata: no disclosures
A. Laroni: speaking honoraria from Biogen and Novartis
C. Solaro: served as a member of the advisory board of the following companies: Biogen Idec and Merck Serono; received speaking honoraria from Bayer Schering, Biogen Idec, Merck Serono, Teva, Almirall, and Sanofi Genzyme and research grants and support by the FISM (Fondazione Italiana Sclerosi Multipla)
A.Uccelli: has received consulting honoraria and/or speaker fees and basic science study grants from Biogen Idec; consulting honoraria and/or speaker fees from Genzyme, Roche, Sanofi Aventis, and Teva; consulting honoraria and/or speaker fees and a basic science study grant from Novartis; consulting honoraria and/or speaker fees and a basic science study grant from Merck Serono
E. Capello: no disclosures
M. Inglese: has received research grants from the NIH, NMSS, Novartis Pharmaceuticals, and Teva Neuroscience