Contributions
Abstract: P782
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Neurodegeneration
Introduction: Disease progression in multiple sclerosis (MS) after acute events can occur in the form of trans-synaptic demyelination, axonal loss or neurodegeneration. Isolated effects of these mechanisms are difficult to investigate due to the disseminated nature of MS.
Objectives: To investigate short- and long-term changes and to identify demographic modulators of trans-synaptic neurodegeneration after clinically isolated optic neuritis (ON) in the afferent visual system.
Aims: 1) To compare longitudinal changes in the afferent visual system between CIS patients after ON (CIS-ON), CIS patients with a clinical manifestation other than ON (CIS-NON) and healthy controls (HCs). 2) To test demographic modulators (i.e. sex) of disease progression in the afferent visual system after ON.
Methods: We investigated age- and sex-matched groups of 23 CIS-ON patients, 23 CIS-NON patients and 23 HCs (women per group: n=17 [73.9%]). Patients were investigated at baseline (median: 4 months after attack) and followed longitudinally over a median of 25 months (CIS-ON) and 37 months (CIS-NON) from first clinical presentation. HC were assessed cross-sectionally. Investigations comprised tractography of the optic radiations (OR) with diffusion tensor imaging (DTI), brain and OR T2 lesions, pericalcarine cortical thickness and peripapillary retinal nerve fiber layer (pRNFL) thickness from optical coherence tomography (OCT).
Results: At baseline, OR axial diffusivity (AD;1.40±0.12;p=0.047), pericalcarine cortical thickness (1.66±0.16mm;p=0.021), and pRNFL (91.59±15.11µm;p=0.026) were already decreased in CIS-ON patients compared to HC (1.45±0.15;1.77±0.24mm;98.64±8.78µm). Baseline differences in AD (p=0.003) and pericalcarine thickness (p=0.009) were driven by female ON patients. No differences between OR AD (p=0.170) and pericalcarine thinning (p=0.440) were seen between CIS-ON and CIS-NON at baseline. On follow-up, CIS-ON patients showed decreased OR AD compared to CIS-NON (p=0.010). Longitudinal AD decrease in CIS-ON was driven by male patients with severe ON based on initial pRNFL (p=0.038). No changes were seen in pericalcarine thickness over time in both groups (p=0.982).
Conclusions: By investigating the visual pathway, we show trans-synaptic OR AD decrease and visual cortex thinning to be present early on in female CIS-ON patients. In contrast, progressive and delayed trans-synaptic neurodegeneration were seen mostly in severely affected male CIS-ON patients.
Disclosure: JK received conference registration fees from Biogen and financial research support from Krankheitsbezogenes Kompetenznetzwerk Multiple Sklerose (KKNMS), not related to this work. FCO is employee of Nocturne UG, unrelated to this work. HGZ, CC and RMG have nothing to disclose. JBS received speaking fees and travel grants from Bayer Healthcare, Sanofi-aventis/Genzyme, Biogen and Teva Pharmaceuticals, unrelated to the present scientific work. KR was supported by the German Ministry of Education and Research (BMBF/KKNMS, Competence Network Multiple Sclerosis) and has received research support from Novartis and Merck Serono as well as speaking fees and travel grants from Guthy Jackson Charitable Foundation, Bayer Healthcare, Biogen Idec, Merck Serono, sanofi-aventis/Genzyme, Teva Pharmaceuticals, Roche and Novartis. JW is CEO of MIAC AG Basel, Switzerland. He served on scientific advisory boards of Actelion, Biogen, Genzyme-Sanofi, Novartis, and Roche. He is or was supported by grants of the EU (Horizon2020), German Federal Ministeries of Education and Research (BMBF) and of Economic Affairs and Energy (BMWI). 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 this work. MS holds a patent for manufacturing of phantoms for computed tomography imaging with 3D printing technology and received research support from Federal Ministry of Economics and Technology. AUB is cofounder and shareholder of Motognosis and Nocturne. He is named as inventor on several patent applications regarding MS serum biomarkers, OCT image analysis and perceptive visual computing.
Abstract: P782
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Neurodegeneration
Introduction: Disease progression in multiple sclerosis (MS) after acute events can occur in the form of trans-synaptic demyelination, axonal loss or neurodegeneration. Isolated effects of these mechanisms are difficult to investigate due to the disseminated nature of MS.
Objectives: To investigate short- and long-term changes and to identify demographic modulators of trans-synaptic neurodegeneration after clinically isolated optic neuritis (ON) in the afferent visual system.
Aims: 1) To compare longitudinal changes in the afferent visual system between CIS patients after ON (CIS-ON), CIS patients with a clinical manifestation other than ON (CIS-NON) and healthy controls (HCs). 2) To test demographic modulators (i.e. sex) of disease progression in the afferent visual system after ON.
Methods: We investigated age- and sex-matched groups of 23 CIS-ON patients, 23 CIS-NON patients and 23 HCs (women per group: n=17 [73.9%]). Patients were investigated at baseline (median: 4 months after attack) and followed longitudinally over a median of 25 months (CIS-ON) and 37 months (CIS-NON) from first clinical presentation. HC were assessed cross-sectionally. Investigations comprised tractography of the optic radiations (OR) with diffusion tensor imaging (DTI), brain and OR T2 lesions, pericalcarine cortical thickness and peripapillary retinal nerve fiber layer (pRNFL) thickness from optical coherence tomography (OCT).
Results: At baseline, OR axial diffusivity (AD;1.40±0.12;p=0.047), pericalcarine cortical thickness (1.66±0.16mm;p=0.021), and pRNFL (91.59±15.11µm;p=0.026) were already decreased in CIS-ON patients compared to HC (1.45±0.15;1.77±0.24mm;98.64±8.78µm). Baseline differences in AD (p=0.003) and pericalcarine thickness (p=0.009) were driven by female ON patients. No differences between OR AD (p=0.170) and pericalcarine thinning (p=0.440) were seen between CIS-ON and CIS-NON at baseline. On follow-up, CIS-ON patients showed decreased OR AD compared to CIS-NON (p=0.010). Longitudinal AD decrease in CIS-ON was driven by male patients with severe ON based on initial pRNFL (p=0.038). No changes were seen in pericalcarine thickness over time in both groups (p=0.982).
Conclusions: By investigating the visual pathway, we show trans-synaptic OR AD decrease and visual cortex thinning to be present early on in female CIS-ON patients. In contrast, progressive and delayed trans-synaptic neurodegeneration were seen mostly in severely affected male CIS-ON patients.
Disclosure: JK received conference registration fees from Biogen and financial research support from Krankheitsbezogenes Kompetenznetzwerk Multiple Sklerose (KKNMS), not related to this work. FCO is employee of Nocturne UG, unrelated to this work. HGZ, CC and RMG have nothing to disclose. JBS received speaking fees and travel grants from Bayer Healthcare, Sanofi-aventis/Genzyme, Biogen and Teva Pharmaceuticals, unrelated to the present scientific work. KR was supported by the German Ministry of Education and Research (BMBF/KKNMS, Competence Network Multiple Sclerosis) and has received research support from Novartis and Merck Serono as well as speaking fees and travel grants from Guthy Jackson Charitable Foundation, Bayer Healthcare, Biogen Idec, Merck Serono, sanofi-aventis/Genzyme, Teva Pharmaceuticals, Roche and Novartis. JW is CEO of MIAC AG Basel, Switzerland. He served on scientific advisory boards of Actelion, Biogen, Genzyme-Sanofi, Novartis, and Roche. He is or was supported by grants of the EU (Horizon2020), German Federal Ministeries of Education and Research (BMBF) and of Economic Affairs and Energy (BMWI). 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 this work. MS holds a patent for manufacturing of phantoms for computed tomography imaging with 3D printing technology and received research support from Federal Ministry of Economics and Technology. AUB is cofounder and shareholder of Motognosis and Nocturne. He is named as inventor on several patent applications regarding MS serum biomarkers, OCT image analysis and perceptive visual computing.