Trans-synaptic axonal degeneration in the visual pathway in multiple sclerosis
Iñigo Gabilondo MD
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorElena H. Martínez-Lapiscina MD
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorEloy Martínez-Heras MSc
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorElena Fraga-Pumar BO
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorSara Llufriu MD
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorSantiago Ortiz MD
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Department of Ophthalmology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorSantiago Bullich PhD
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorMaria Sepulveda MD
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorCarles Falcon PhD
Medical Imaging Platform and Biomedical Research Networking Center for Bioengineering, Biomaterials, and Nanomedicine, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorJoan Berenguer MD
Department of Radiology and Imaging Diagnostic Center, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorAlbert Saiz MD
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorBernardo Sanchez-Dalmau MD
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Department of Ophthalmology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorCorresponding Author
Pablo Villoslada MD
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Address correspondence to Dr Villoslada, Center of Neuroimmunology, IDIBAPS, Casanova 143, 08036 Barcelona, Spain. E-mail: [email protected]Search for more papers by this authorIñigo Gabilondo MD
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorElena H. Martínez-Lapiscina MD
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorEloy Martínez-Heras MSc
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorElena Fraga-Pumar BO
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorSara Llufriu MD
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorSantiago Ortiz MD
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Department of Ophthalmology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorSantiago Bullich PhD
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorMaria Sepulveda MD
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorCarles Falcon PhD
Medical Imaging Platform and Biomedical Research Networking Center for Bioengineering, Biomaterials, and Nanomedicine, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorJoan Berenguer MD
Department of Radiology and Imaging Diagnostic Center, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorAlbert Saiz MD
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorBernardo Sanchez-Dalmau MD
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Department of Ophthalmology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Search for more papers by this authorCorresponding Author
Pablo Villoslada MD
Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain
Address correspondence to Dr Villoslada, Center of Neuroimmunology, IDIBAPS, Casanova 143, 08036 Barcelona, Spain. E-mail: [email protected]Search for more papers by this authorAbstract
Objective
To evaluate the association between the damage to the anterior and posterior visual pathway as evidence of the presence of retrograde and anterograde trans-synaptic degeneration in multiple sclerosis (MS).
Methods
We performed a longitudinal evaluation on a cohort of 100 patients with MS, acquiring retinal optical coherence tomography to measure anterior visual pathway damage (peripapillary retinal nerve fiber layer [RNFL] thickness and macular volume) and 3T brain magnetic resonance imaging (MRI) for posterior visual pathway damage (volumetry and spectroscopy of visual cortex, lesion volume within optic radiations) at inclusion and after 1 year. Freesurfer and SPM8 software was used for MRI analysis. We evaluated the relationships between the damage in the anterior and posterior visual pathway by voxel-based morphometry (VBM), multiple linear regressions, and general linear models.
Results
VBM analysis showed that RNFL thinning was specifically associated with atrophy of the visual cortex and with lesions in optic radiations at study inclusion (p < 0.05). Visual cortex volume (β = +0.601, 95% confidence interval [CI] = +0.04 to +1.16), N-acetyl aspartate in visual cortex (β = +1.075, 95% CI = +0.190 to +1.961), and lesion volume within optic radiations (β = −2.551, 95% CI = −3.910 to −1.192) significantly influenced average RNFL thinning at study inclusion independently of other confounders, especially optic neuritis (ON). The model indicates that a decrease of 1cm3 in visual cortex volume predicts a reduction of 0.6μm in RNFL thickness. This association was also observed after 1 year of follow-up. Patients with severe prior ON (adjusted difference = −3.01, 95% CI = −5.08 to −0.95) and mild prior ON (adjusted difference = −1.03, 95% CI = −3.02 to +0.95) had a lower adjusted mean visual cortex volume than patients without ON.
Interpretation
Our results suggest the presence of trans-synaptic degeneration as a contributor to chronic axon damage in MS. ANN NEUROL 2014;75:98–107
Supporting Information
Additional supporting information can be found in the online version of this article.
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