# Isolated cranial nerve disorder as presenting sign in multiple sclerosis: optic nerve versus “the others”

**Authors:** Arianna Di Stadio, Pietro Scribani Rossi, Diego Kaski, Chiara Zilli, Massimo Ralli, Evanthia Bernitsas, Marta Altieri

PMC · DOI: 10.3389/fneur.2025.1557326 · Frontiers in Neurology · 2025-04-02

## TL;DR

This study finds that multiple sclerosis patients who first experience non-optic cranial nerve symptoms may have a milder disease progression compared to those with optic neuritis.

## Contribution

The study provides new evidence that MS onset with non-optic cranial nerve involvement is linked to fewer relapses and less disability over four years.

## Key findings

- Patients with OCN involvement had fewer relapses and better EDSS scores after four years compared to those with optic neuritis.
- ON patients were younger at onset and had a higher risk of relapse and disability progression.
- The results suggest a more favorable disease course for MS patients presenting with non-optic cranial nerve symptoms.

## Abstract

The prevalence of cranial nerve involvement in Multiple Sclerosis (MS) varies across studies. It has been speculated that first presentation of disease with cranial nerve involvement – except for optic neuritis – may be associated with milder progression.

This study compares the clinical outcome of patients with MS in a 4-year follow-up of patients with initial symptoms of optic neuritis (ON) versus those with other cranial nerve (OCN) involvement.

Retrospective analysis of MS patient database of a tertiary referral university MS center. We included treatment-naïve patients diagnosed with MS according to the revised McDonald criteria, who presented with their first clinical symptoms suggestive of ON or OCN. Patients were required to have regular clinical and radiological follow-up visits (at least two outpatient visits per year and one annual 1.5T MRI), and no comorbidities. The number of relapses and the Expanded Disability Status Scale (EDSS) scores were assessed at six-month intervals during clinic visits. The primary outcome was the number of relapses observed during the study period, comparing the ON and OCN groups. Several statistical analyses were performed, including multiple linear regression, Cox proportional hazards model, one-way ANOVA, and odds ratios, to compare the groups.

Of the 84 patients included, none had comorbities (e.g., overlap with other inflammatory diseases, neoplasm etc.). Fifty-five presented with ON and 29 with OCN (e.g., diplopia, trigeminal pain, hearing or vestibular symptoms) at onset. Patients with ON were younger than those with OCN symptoms (p = 0.02), had a higher risk of relapse (more than two relapses) (OR: 1.53) and greater disability (incremental EDSS) over the 4-year follow-up (OR: 1.60).

Patients with OCN involvement at the onset experienced fewer relapses and had better EDSS scores at the 4-year follow-up compared to those with ON at onset. These preliminary findings suggest that MS onset with OCN involvement may be associated with a more favorable disease course.

## Linked entities

- **Diseases:** Multiple Sclerosis (MONDO:0005301), optic neuritis (MONDO:0005885)

## Full-text entities

- **Diseases:** MS (MESH:D009103), nerve (MESH:C537568), cranial nerve disorder (MESH:D003389), OCN (MESH:D003390), ON (MESH:D009902), hearing or vestibular symptoms (MESH:D015837), neoplasm (MESH:D009369), trigeminal pain (MESH:D010146), diplopia (MESH:D004172), inflammatory diseases (MESH:D007249)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12000048/full.md

## References

30 references — full list in the complete paper: https://tomesphere.com/paper/PMC12000048/full.md

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Source: https://tomesphere.com/paper/PMC12000048