Contributions
Abstract: P505
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: Increased total sodium concentration has been demonstrated in the brains of patients with relapsing remitting, secondary progressive and primary progressive multiple sclerosis (MS). It is thought that this may reflect neuroaxonal pathology. However, it is still unknown if increased sodium is seen in subjects presenting with a clinically isolated syndrome (CIS).
Objective: The aim of this study is to estimate the total sodium concentration in the normal appearing white matter, cortical grey matter, deep grey matter and T2 lesions in patients presenting with a CIS.
Methods: We recruited 20 CIS subjects (10F:10M), with a mean age 35.6 (±8.6) years within 3 months from symptom onset and 11 healthy controls (7F:4M), with a mean age 35.2 (±7.5) years. Patients had a median EDSS of 1.0 (range 0-2.5), with the majority of subjects presenting with an optic neuritis (N=17). 11 of the CIS subjects had an abnormal MRI scan with asymptomatic, non-enhancing T2 lesions at baseline (mean T2 lesion volume = 6.20 (±5.5) ml). Subjects underwent two protocols in the same session using a 3T scanner: 1) PD/T2 and 3D T1 images; and 2) quantitative total sodium MRI. After lesion filling the 3D T1 images, probabilistic tissue brain segmentations were performed using GIF. Tissue masks were registered and resampled to the sodium space using NiftyReg. Linear regression models compared differences between groups adjusting for age, gender and grey or white matter tissue fraction.
Results: Increased sodium concentration was seen in the asymptomatic brain T2 lesions compared with normal appearing white matter in CIS subjects (49.98±7.77mM versus 33.16±3.7mM, p=0.005). There were no differences in sodium concentration for normal appearing white matter (33.16±3.7mM versus 31.4±2.3mM), cortical grey matter (41.8±3.2mM versus 41.1±2.6mM) and deep grey matter (35.5±3.3mM versus 34.4±2.5mM) in CIS patients when compared to controls.
Conclusion: This study extends the findings of increased sodium concentration in MS to patients presenting with a CIS. Increased total sodium levels in the T2 lesions could reflect the underlying oedema, associated with an inflammatory event; additionally, this could reflect neuroaxonal dysfunction and/or loss occurring at the onset of a first demyelinating event. Sodium imaging may have a role as an outcome measure in clinical trials that target the sodium pathway of the neurons.
Disclosure:
Niamh Cawley - nothing to disclose
Bhavana S. Solanky - nothing to disclose
Ferran Prados - nothing to disclose
Sara Collorone - nothing to disclose
Baris Kanber - nothing to disclose
Sebastian Ourselin - nothing to disclose
CAM Gandini Wheeler Kingshott - serves as a consultant for Biogen and receives research support from the UK MS Society, UCL/UCLH NIHR BRC, EPSRC, ISRT, Wings for Life, New Zealand Brain Research Centre, Novartis, and Biogen.
David H. Miller - received grants from UCL/UCLH Biomedical Research Centre, during the conduct of the study; has received grants from Biogen, GlaxoSmithKline, the National Institute for Health Research, Novartis, and Apitope; has board membership with Biogen Idec, GlaxoSmithKline, Bayer Schering Pharma, and Mitsubishi Pharma Europe; has been a consultant for Merck and Chugai; and has received personal fees from McAlpine"s Multiple Sclerosis, 4th edition.
Alan Thompson - has received honoraria and support for travel for consultancy from Biogen Idec, Eisai, Genzyme, Novartis and Medday, and for speaking from EXCEMED, Novartis, Remedica and Teva. He receives an honorarium from Sage Publications as Editor-in-Chief of Multiple Sclerosis Journal.
Ahmed Toosy - Meeting expenses ECTRIMS conference 2015 paid by Biogen Idec.
Olga Ciccarelli - serves as a consultant for Biogen, GE Healthcare and Novartis, and payments are made to the institution; she receives an honorarium as Associate Editor of Neurology.
Abstract: P505
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: Increased total sodium concentration has been demonstrated in the brains of patients with relapsing remitting, secondary progressive and primary progressive multiple sclerosis (MS). It is thought that this may reflect neuroaxonal pathology. However, it is still unknown if increased sodium is seen in subjects presenting with a clinically isolated syndrome (CIS).
Objective: The aim of this study is to estimate the total sodium concentration in the normal appearing white matter, cortical grey matter, deep grey matter and T2 lesions in patients presenting with a CIS.
Methods: We recruited 20 CIS subjects (10F:10M), with a mean age 35.6 (±8.6) years within 3 months from symptom onset and 11 healthy controls (7F:4M), with a mean age 35.2 (±7.5) years. Patients had a median EDSS of 1.0 (range 0-2.5), with the majority of subjects presenting with an optic neuritis (N=17). 11 of the CIS subjects had an abnormal MRI scan with asymptomatic, non-enhancing T2 lesions at baseline (mean T2 lesion volume = 6.20 (±5.5) ml). Subjects underwent two protocols in the same session using a 3T scanner: 1) PD/T2 and 3D T1 images; and 2) quantitative total sodium MRI. After lesion filling the 3D T1 images, probabilistic tissue brain segmentations were performed using GIF. Tissue masks were registered and resampled to the sodium space using NiftyReg. Linear regression models compared differences between groups adjusting for age, gender and grey or white matter tissue fraction.
Results: Increased sodium concentration was seen in the asymptomatic brain T2 lesions compared with normal appearing white matter in CIS subjects (49.98±7.77mM versus 33.16±3.7mM, p=0.005). There were no differences in sodium concentration for normal appearing white matter (33.16±3.7mM versus 31.4±2.3mM), cortical grey matter (41.8±3.2mM versus 41.1±2.6mM) and deep grey matter (35.5±3.3mM versus 34.4±2.5mM) in CIS patients when compared to controls.
Conclusion: This study extends the findings of increased sodium concentration in MS to patients presenting with a CIS. Increased total sodium levels in the T2 lesions could reflect the underlying oedema, associated with an inflammatory event; additionally, this could reflect neuroaxonal dysfunction and/or loss occurring at the onset of a first demyelinating event. Sodium imaging may have a role as an outcome measure in clinical trials that target the sodium pathway of the neurons.
Disclosure:
Niamh Cawley - nothing to disclose
Bhavana S. Solanky - nothing to disclose
Ferran Prados - nothing to disclose
Sara Collorone - nothing to disclose
Baris Kanber - nothing to disclose
Sebastian Ourselin - nothing to disclose
CAM Gandini Wheeler Kingshott - serves as a consultant for Biogen and receives research support from the UK MS Society, UCL/UCLH NIHR BRC, EPSRC, ISRT, Wings for Life, New Zealand Brain Research Centre, Novartis, and Biogen.
David H. Miller - received grants from UCL/UCLH Biomedical Research Centre, during the conduct of the study; has received grants from Biogen, GlaxoSmithKline, the National Institute for Health Research, Novartis, and Apitope; has board membership with Biogen Idec, GlaxoSmithKline, Bayer Schering Pharma, and Mitsubishi Pharma Europe; has been a consultant for Merck and Chugai; and has received personal fees from McAlpine"s Multiple Sclerosis, 4th edition.
Alan Thompson - has received honoraria and support for travel for consultancy from Biogen Idec, Eisai, Genzyme, Novartis and Medday, and for speaking from EXCEMED, Novartis, Remedica and Teva. He receives an honorarium from Sage Publications as Editor-in-Chief of Multiple Sclerosis Journal.
Ahmed Toosy - Meeting expenses ECTRIMS conference 2015 paid by Biogen Idec.
Olga Ciccarelli - serves as a consultant for Biogen, GE Healthcare and Novartis, and payments are made to the institution; she receives an honorarium as Associate Editor of Neurology.