False-positive cases classified by the 2022 optic neuritis criteria: clinical and radiological features

Optic neuritis (ON) has historically been misdiagnosed in up to 60% of cases, prompting the development of the 2022 diagnostic criteria. However, residual diagnostic failures may persist in clinical practice.

To determine the frequency and causes of ON misdiagnosis and identify points of failure within the 2022 criteria.

We conducted a retrospective study including consecutive patients with suspected ON tested for anti-AQP4 autoantibodies. We assessed the frequency of misdiagnosis, underlying etiologies, and points of failure within the 2022 diagnostic criteria. Cases were classified according to the criteria, and final diagnoses were defined. Clinical presentation (unilateral vs bilateral involvement, relative afferent pupillary defect, and fundoscopy) and paraclinical tests (serum and CSF antibodies, MRI-including gadolinium enhancement and T2 signal-and OCT) were systematically analyzed.

Among 59 patients, 3 (5.1%) were misdiagnosed; one fulfilled definite ON criteria and two possible ON criteria. Final diagnoses were non-arteritic anterior ischemic optic neuropathy, optic disk drusen, and functional neurological disorder, the latter reclassified after detailed radiological and semiological review. Relative afferent pupillary defect was present in two cases, and OCT was abnormal in two. All three showed optic nerve T2 hyperintensity on MRI, but none had gadolinium enhancement. Anti-AQP4, anti-MOG, and oligoclonal bands were negative in all cases.

Misdiagnosis was reduced to 5.1% with the 2022 criteria, but errors persisted despite typical clinical findings, OCT abnormalities, and optic nerve T2 hyperintensity. Greater specificity may be achieved by assigning more diagnostic weight to optic nerve gadolinium enhancement.