Adding the Optic Nerve in Multiple Sclerosis Diagnostic Criteria
A Longitudinal, Prospective, Multicenter Study
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VIEW CORRECTIONAbstract
Background and Objectives
The optic nerve is not one of the areas of the CNS that can be used to demonstrate dissemination in space (DIS) within the 2017 McDonald criteria for the diagnosis of multiple sclerosis (MS). Objectives were (1) to assess whether optic nerve-MRI (ON-MRI), optical coherence tomography (OCT), and visual evoked potentials (VEP) detect optic nerve involvement in clinically isolated syndrome (CIS) and (2) to evaluate the contribution of the optic nerve topography to the current diagnostic criteria in a prospective, multicenter cohort.
Methods
MAGNIMS centers were invited to provide prospective data on patients with CIS who underwent a visual assessment with at least 2 of 3 investigations (ON-MRI, OCT, or VEP) within 6 months of onset. Modified DIS criteria were constructed by adding the optic nerve topography, defined by each investigation separately and any combination of them, as the fifth area of the CNS. A risk assessment analysis and the performance of the different DIS criteria were analyzed using the diagnosis of MS according to the 2017 McDonald criteria as the primary outcome and new T2 lesions and/or a second relapse as the secondary outcome.
Results
We included 157 patients with CIS from 5 MAGNIMS centers; 60/157 (38.2%) patients presented with optic neuritis. Optic nerve involvement on ON-MRI was found in 40.2% patients at study entry and in 72.5% of those with optic neuritis.
At follow-up (mean 27.9 months, SD 14.5), 111/157 patients (70.7%) were diagnosed with MS according to the 2017 McDonald criteria. Fulfilling either 2017 DIS or any modified DIS criteria conferred a similar high risk for reaching primary and secondary outcomes. The modified DIS criteria had higher sensitivity (92.5% [with ON-MRI] vs 88.2%), but slightly lower specificity (80.0% [with GCIPL IEA ≥4 μm] vs 82.2%), with overall similar accuracy (86.6% [with ON-MRI] vs 86.5%) than 2017 DIS criteria. Consistent results were found for secondary outcomes.
Discussion
In patients with CIS, the presence of an optic nerve lesion defined by MRI, OCT, or VEP is frequently detected, especially when presenting with optic neuritis. Our study supports the addition of the optic nerve as a fifth topography to fulfill DIS criteria.
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Information & Authors
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© 2023 American Academy of Neurology.
Publication History
Received: June 20, 2023
Accepted: September 20, 2023
Published online: December 13, 2023
Published in issue: January 9, 2024
Disclosure
A. Vidal-Jordana has received support for contracts Juan Rodes (JR16/00024) and from Fondo de Investigación en Salud (PI17/02162) from Instituto de Salud Carlos III, Spain, and has engaged in consulting and/or participated as speaker in events organized by Roche, Novartis, Merck, and Sanofi. A. Rovira serves/served on scientific advisory boards for Novartis, Sanofi-Genzyme, Synthetic MR, Roche, Biogen, Tensor Medical, Bayer, and OLEA Medical and has received speaker honoraria from Sanofi-Genzyme, Merck-Serono, Teva Pharmaceutical Industries Ltd, Novartis, Bayer, Roche, Bristol-Myers, and Biogen. G. Arrambide has received compensation for consulting services or participation in advisory boards from Sanofi, Merck, and Roche; research support from Novartis; travel expenses for scientific meetings from Novartis, Roche, Stendhal, and ECTRIMS; and speaking honoraria from Sanofi, Merck, and Roche. G. Arrambide is a member of the executive committee of the International Women in Multiple Sclerosis (iWiMS) network. S. Collorone was supported by the Rosetrees Trust (MS632), and she was awarded a MAGNIMS-ECTRIMS fellowship in 2016. A.T. Toosy has received speaker honoraria from Biomedia, Sereno Symposia International Foundation, and Bayer and meeting expenses from Biogen Idec and is the UK PI for 2 clinical trials sponsored by MEDDAY pharmaceutical company (MD1003 in optic neuropathy [MS-ON] and progressive MS [MS-SPI2]). OC is Deputy Editor of Neurology, and she serves on the Editorial Board of Multiple Sclerosis Journal; she receives research support from the NIHRUCLH/UCL Biomedical Research Center, NIHR, MS Society of Great Britain and Northern Ireland, National MS Society, Rosetrees Trust. A. Papadopoulou has received speaker fee from Sanofi-Genzyme and travel support from Bayer AG, Teva, and Hoffmann-La Roche. Her research was/is being supported by the University and University Hospital of Basel, the Swiss Multiple Sclerosis Society, the "Stiftung zur Förderung der gastroenterologischen und allgemeinen klinischen Forschung sowieder medizinischen Bildauswertung," and the Swiss National Science Foundation (Project number: P300PB_174480). S. Ruggieri has received honoraria from Biogen, Merck Serono, Novartis, and Teva for consulting services, speaking, and/or travel support. C. Tortorella has received honoraria for speaking and travel grants from Biogen, Sanofi-Aventis, Merck Serono, Bayer-Schering, Teva, Genzyme, Almirall, and Novartis. CG has received speaker honoraria and/or travel expenses for attending meeting from Bayer Schering Pharma, Sanofi-Aventis, Merck, Biogen, Novartis, and Almirall. A. Bisecco received speaker honoraria and/or compensation for consulting service and/or speaking activities from Biogen, Roche, Merck, Celgene, and Genzyme. A. Gallo has received honoraria from Biogen, Merck Serono, Mylan, Novartis, Roche, Sanofi-Genzyme, and Teva for consulting services, speaking, and/or travel support. J. Sastre-Garriga has engaged in consulting and/or participated as speaker in events organized by Biopass, Biogen, Celgene, Merck, and Orchid Pharma. M. Tintore has received compensation for consulting services and speaking honoraria from Almirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Janssen, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Viela Bio, and Teva Pharmaceuticals. M. Tintore is coeditor of Multiple Sclerosis Journal-ETC. XM has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Abbvie, Actelion, Alexion, Bayer, Biogen, Bristol-Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic, Janssen Pharmaceuticals, Medday, Merck, Mylan, Nervgen, Novartis, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, Excemed, MSIF, and NMSS. W. Calderon, J. Castilló, D. Moncho, K. Rahnama, N. Cerdá-Fuertes, J.M. Lieb, R. Capuano, A. De Barros, A. Salerno, and C. Auger report no disclosures. Go to Neurology.org/N for full disclosures.
Study Funding
This study has been partly supported by Instituto de Salud Carlos III through the project PI17/02162 and cofunded by European Regional Development Fund/European Social Fund.
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We enthusiastically read the article by Vidal-Jordana et al., which reports the results of a prospective study of patients with clinically isolated syndrome. The study was performed to determine whether the optic nerve (ON) could be added as the fifth topographic site for multiple sclerosis (MS) diagnosis to fulfill the criteria for demonstrating dissemination in space.1 The study included the use of MRI–specific orbita sequences, optical coherence tomography, and visual evoked potentials to achieve higher sensitivity in earlier MS diagnosis, thereby speeding up the start of therapy.
We would like to emphasize that the currently only partially recognized tool of optic nerve sonography (ONS) is also available to neurologists. In patients with acute optic neuritis, ONS provides a lateral resolution between 0.3 and 0.4 mm, which is sufficient to highlight ON abnormalities in the case of acute optic neuritis, as with MRI.
Almost 80% of patients affected by acute optic neuritis show distension of the ON sheath diameter due to an inflammatory event causing edema. One-third of patients with optic neuritis present with papillitis, recognizable as optic disc elevation in ONS.2,3 Finally, it is useful to provide information about the eventual normalization of observing the ON during follow-up.4
We appreciate the study of Vidal-Jordana et al., but we would like to stress that neurologists should be encouraged to use ONS in clinical practice.1
References
1.Vidal-Jordana A, Rovira A, Calderon W, et al. Adding the Optic Nerve in Multiple Sclerosis Diagnostic Criteria: A Longitudinal, Prospective, Multicenter Study. Neurology. 2024;102(1):e200805. doi:10.1212/WNL.0000000000207805.
2. Lochner P, Leone MA, Coppo L, et al. B-mode transorbital ultrasononography for the diagnosis of acute optic neuritis. A systematic review. Clin Neurophysiol. 2016;127(1):803-809. doi:10.1016/j.clinph.2015.05.005.
3. Lochner P, Cantello R, Brigo F, et al. Transorbital sonography in acute optic neuritis: a case-control study. AJNR Am J Neuroradiol. 2014;35(12):2371-2375. doi:10.3174/ajnr.A4051.
4. Lochner P, Leone MA, Fassbender K, et al. Transorbital Sonography and Visual Outcome for the Diagnosis and Monitoring of Optic Neuritis. J Neuroimaging. 2017;27(1):92-96. doi:10.1111/jon.12405.
Author disclosures are available upon request ([email protected]).