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A case for including optic nerve lesions in the McDonald criteria

Presented by
Prof. Frederik Barkhof, Vrije Universiteit Amsterdam, the Netherlands

Optic nerve lesions (ONLs) are often the first detectable marker of MS, nevertheless, they are currently not included in the McDonald criteria for diagnosing MS. Several presenters at ECTRIMS 2022 made the case for adding ONLs as a key diagnostic measure of MS at the next revision of these criteria.

In the 2010 revision of the McDonald criteria [1], symptomatic and asymptomatic lesions were considered equally to determine dissemination in space (DIS) or dissemination in time (DIT). From then on, DIS criteria required any lesions (clinically silent or not) in at least 2 out of 4 typical areas of the CNS: periventricular, juxtacortical, infratentorial, or spinal cord. Radiologist Prof. Frederik Barkhof (Vrije Universiteit Amsterdam, the Netherlands) presented the results from his discussion with the Magnetic Imaging in Multiple Sclerosis (MAGNIMS) group on these criteria [2].

The MAGNIMS group noticed “a bit of an imbalance,” in the words of Prof. Barkhof: “Why would you require 3 regions if you have an ONL and only 2 if you have a spinal cord or a brainstem presentation?” Consequently, MAGNIMS MRI criteria for DIS proposed requiring the involvement of at least 2 out of 5 CNS areas, now including also the optic nerve. Prof. Barkhof said that it was generally considered a sensible proposal which failed to be included in the 2017 McDonald criteria [3], due to a paucity of data at the time. Prof. Barkhof expressed his confidence that ONLs will be included in the upcoming revision, as optic neuritis is the most common first presentation of clinically isolated syndrome (CIS)/MS and MRI has a high specificity and sensitivity.

Next, Dr Angela Vidal-Jordana (Vall d'Hebron University Hospital, Spain) discussed the implementation of ONLs in the clinic [4]. When a patient presents with new visual symptoms, one should ask whether this is suggestive of an inflammatory aetiology and whether these symptoms are typical for MS. If the answer to both questions is positive, optic nerve topography should be taken into account in the diagnostic process. Dr Vidal-Jordana stressed that optic neuritis is frequently overdiagnosed, in up to 60% of cases. Therefore, when a patient comes to a neurologist with a diagnosis of optic neuritis, that diagnosis should be questioned. As long as the highest quality standards apply, MRI, visual evoked potentials (VEP), or optical coherence tomography (OCT) can be used to evaluate structure and function of the optic nerve. Test selection should probably be based on availability, centre experience, and time elapsed since CIS. “If less than 3 months have passed, I would go for a VEP; if more time has passed, I would probably choose OCT,” said Dr Vidal-Jordana.

Non-MRI methods for assessing ONLs were discussed by neuro-ophthalmologist Prof. Laura Balcer (NYU Grossman School of Medicine, NY, US) [5]. In about 25% of MS patients, ONLs are the first clinical demyelinating event. “An enormous amount of data has emerged over the past 5 years, demonstrating the importance of the optic nerve in the MS diagnosis with implications for early therapy.” It is however critical to be sure of the diagnosis of optic neuritis before considering it a symptom of MS. It should not be confused with central serious maculopathy for example, which is often painless and could worsen when treated with steroids.

Prof. Balcer concluded that the optic nerve should “get a fair shake” in the diagnosis of MS, since  multiple modalities exists for identifying ONLs, including OCT, VEP, and advanced MRI. Further, evidence for these measures is strong, and diagnostic criteria need not necessarily be additive or fulfilled sequentially. Clinical diagnosis of optic neuritis and identification of optic neuropathies is also critical to establish DIS and DIT. Taken together, the optic nerve should be a first ingredient in the MS diagnostic criteria, according to the discussants.

  1. Polman CH, et al. Ann Neurol. 2011;69(2):292–302.
  2. Barkhof F. Rationale and detection by MRI. Hot topic 6, ECTRIMS 2022, 26–28 October, Amsterdam, the Netherlands.
  3. Thompson AJ, et al. Lancet Neurol. 2018;17(2):162173.
  4. Vidal-Jordana A. Clinical implementation. Hot topic 6, ECTRIMS 2022, 26–28 October, Amsterdam, the Netherlands.
  5. Balcer L. Non-MRI assessment of optic nerve lesions. Hot topic 6, ECTRIMS 2022, 26–28 October, Amsterdam, the Netherlands.

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