Several MRI findings of optic neuritis (ON) he been described and correlated with specific underlying etiologies. Specifically, optic nerve enhancement is considered an accurate biomarker of acute ON.
ObjectiveTo identify differences in MRI patterns of optic nerve enhancement in certain demyelinating etiologies presenting with acute ON.
MethodsRetrospective analysis of enhancement patterns on fat-suppressed T1-weighted images from patients presenting clinical and radiological acute ON, treated at our institution between January 2014 and June 2022. Location and extension of enhancing optic nerve segments, as well as presence of perineural enhancement were evaluated in three predetermined demyelinating conditions. Fisher’s exact test and chi2 were calculated.
ResultsFifty-six subjects met eligibility criteria. Mean age was 31 years (range 6–79) and 70% were females. Thirty-four (61%) patients were diagnosed with multiple sclerosis (MS), 8 (14%) with neuromyelitis optica (NMO), and 14 (25%) with anti-myelin oligodendrocyte glycoprotein disease (MOGAD). Bilateral involvement was more frequent in MOGAD, compared to MS and NMO (43 vs 3% and 12.5% respectively, p = 0.002). MS patients showed shorter optic nerve involvement, whereas MOGAD showed more extensive lesions (p = 0.006). Site of involvement was intraorbital in 63% MS, 89% NMO, 90% MOGAD (p = 0.051) and canalicular in 43% MS, 33% NMO and 75% MOGAD (p = 0.039). Intracranial or chiasmatic involvement and presence of perineural enhancement were not statistically different between entities.
ConclusionIn the setting of acute ON, patients presenting MOGAD were more likely to show bilateral, longitudinally extended and anterior (intraorbital and canalicular) optic nerve involvement compared to patients with MS or NMO.
Keywords: anti-myelin oligodendrocyte glycoprotein, MRI, multiple sclerosis, neuromyelitis optica, optic neuritis
IntroductionOptic neuritis (ON) is an inflammatory condition of the optic nerve, usually affecting young adults, with a female preponderance. 1 It has been linked to varying etiologies including demyelinating, infectious, and autoimmune conditions.1,2 Demyelinating ON is the most common form, and is more often observed in patients presenting multiple sclerosis (MS), neuromyelitis optica (NMO) or myelin oligodendrocyte glycoprotein antibody disease (MOGAD).2,3
ON typically presents with acute or subacute monocular vision loss combined with pain on eye movement. 4 In the context of an acute event, brain MRI plays a pivotal role in stratifying risk of conversion to MS. 5 Aside from whole brain imaging, optic nerve MRI is routinely used in the evaluation of these patients. Presence of gadolinium enhancement on fat-suppressed (FS) T1-weighted imaging (WI) is considered a sensitive finding and a reliable biomarker of optic nerve edema, inflammation, and demyelination.6,7
MRI findings vary between demyelinating conditions including a trend for more anterior involvement in patients with MS and MOGAD, and more posterior, optic chiasm and optic tract changes in NMO cases.8–11 Bilateral ON has been strongly associated with NMO and MOGAD.11–13 Moreover, enhancement of the optic nerve sheath, partially extending into peri-optic soft tissues (i.e., perineural enhancement) has been uniquely described in patients with MOGAD.12,14,15 Finally, length of optic nerve involvement has been reported to be more extensive in NMO and in MOGAD, than in MS.8–10,16
The aim of this study was to identify discrete differences in patterns of optic nerve enhancement on MRI, between patients presenting MS, NMO and MOGAD in the setting of acute ON.
Methods Patient selection and study designA retrospective analysis was conducted of clinical data obtained from electronic medical records of patients treated at our institution between January 2014 and June 2022. The study protocol was first approved by the institutional review board and the need for patient informed consent was waived.
Patients presenting with: (1) acute ON (symptoms up to 1 month from onset), (2) definitive diagnosis of one of the following demyelinating disorders: MS, NMO, or MOGAD, and (3) MRI protocol including optic nerve evaluation, were identified. Cases of idiopathic or non-definitive demyelinating ON; lost to follow up; or with poor quality MRI and/or insufficient MRI data due to lack of contrast administration; or lacking dedicated optic nerve protocol, were excluded.
MS diagnosis was based on the revised 2010 McDonald criteria 17 and on the 2015 NMOSD criteria 11 for NMO cases. MOGAD diagnosis was based on MOG antibody seropositivity using a cell-based assay, as recommended. 15 A total of 56 patients met the selection criteria described above and were included in this analysis.
Data on patient characteristics including gender, age at ON presentation and days from symptom onset to MRI were recorded.
MR imaging acquisition and data analysesMRI were acquired either on a Discovery 750 3T (GE Healthcare), an Achieva 1.5 T (Philips Medical Systems) or a Signa HDxt 1.5 T (GE Healthcare). All optic nerve MRI protocols included 3-mm axial and coronal FS T2-WI images, as well as pre- and post-contrast (gadoterate meglumine 0.1 mmol/kg) FS T1-WI images.
We analyzed enhancement patterns from FS T1-WI sequences in 56 patients. Parameters assessed included: side and site of lesion (intraorbital, canalicular, intracranial or chiasmatic) (Figure 1), number of involved segments and presence or absence of perineural enhancement.
Figure 1.
Graphic showing optic nerve segments involved on axial FS T1-WI: intraorbital (dashed), canalicular (solid), intracranial (dot dash), chiasmatic (dotted) and optic tract (long dash).
All MR images were examined by both a third-year radiology resident and a neuroradiologist with 8 years’ experience, both blinded to clinical findings and diagnosis.
Statistical analysisWe used descriptive statistics including mean values and standard deviations for demographic data analysis, and rates and percentages for categorical and nominal variables. Chi2 and Fisher exact test were applied to assess statistical differences between optic nerve enhancement patterns and acute ON etiologies, and p-values < 0.05 were considered significant. Statistical analysis was performed using Stata (Version 15.0, StataCorp, College Station, Texas).
Results Clinical diagnosis and patient demographicsOne hundred fifty six patients presenting acute ON in whom MRIs were ailable, were identified. Of these, 52 were excluded from the analysis either because images were of poor quality, lacked post-contrast sequences, or had not been obtained following a dedicated optic nerve imaging protocol. Another 48 patients without definite diagnosis or lost to follow-up were also subsequently excluded. Of the 56 patients remaining, 34 were diagnosed with MS (61%), 8 with NMO (14%), and 14 with MOGAD (25%). Mean patient age was 31.1 years (range 6–79) and 39 were females (69.6%). Median time from symptom onset to MRI was 8.5 days (range 0–35 days). Patient-selection flowchart and individual characteristics are shown in Figure 2 and Table 1, respectively.
Figure 2.
Flowchart of patient-selection process.
Table 1.Patient clinical characteristics.
Variables MS (n = 34) NMO (n = 8) MOGAD (n = 14) p-value Sex Men 9 (26%) 1 (12.5%) 7 (50%) 0.135 Women 25 (74%) 7 (87.5%) 7 (50%) Age 40 years 5 (14.7%) 5 (62.5%) 1 (7.1%) Time to MRIσ 8.23 (± 7.3) 8.25 (± 10.6) 10.1 (± 9.5) Open in a new tab*Statistically significant.
σMean time (in days) from symptoms to MRI and (range).
MRI findingsMRI findings are summarized in Table 2.
Table 2.MRI findings.
Variables MS (n = 34) NMO (n = 8) MOGAD (n = 14) p-value Laterality Unilateral 33 (97%) 7 (87.5%) 8 (57%) 0.002* Bilateral 1 (3%) 1 (12.5%) 6 (43%) Perineural enhancement§ 3 (9%) 3 (33%) 4 (20%) 0.116 Anatomical segment§,‡ Intraorbital 22 (63%) 8 (89%) 18 (90%) 0.051* Canalicular 15 (43%) 3 (33%) 15 (75%) 0.039* Intracranial 9 (26%) 3 (33%) 11 (55%) 0.087 Chiasmatic 1 (3%) 1 (11%) 1 (5%) 0.398 Segments§ 1 26 (74%) 5 (56%) 5 (25%) 0.006* 2 6 (17%) 2 (22%) 6 (30%) 3 3 (9%) 2 (22%) 8 (40%) 4 0 0 1 (5%) Open in a new tab*Statistically significant. §Absolute values (and percentages) in this row relates to the number of clinically and radiologically affected optic nerves. ‡A single nerve may he more than one involved segment; hence the sum of all percentages is over 100%.
Laterality of optic nerve involvementEight patients presented bilateral involvement (3% of MS, 12.5% of NMO and 43% of MOGAD cases) while unilateral enhancement was observed in the remainder 48 patients (97% of MS, 87.5% of NMO and 57% of MOGAD cases; p = 0.002) (Figure 3).
Figure 3.
Laterality (a–c). Axial post-contrast FS T1-WI show unilateral enhancement of the right (solid arrow in a) and left (open arrow in b) optic nerves in two different patients diagnosed with MS. Bilateral long length optic nerve enhancement (arrowheads) in a patient with MOGAD (c).
Perineural enhancementTen nerves showed perineural enhancement (9% of MS, 33% of NMO and 20% of MOGAD cases; p = 0.116) (Figure 4).
Figure 4.
Examples of perineural enhancement. Coronal post-contrast FS T1-WI (a and b) in a patient with MOGAD show bilateral enhancement of soft tissue around the optic nerves. Dotted lines (b) depict perineural enhancement in the same patient. Axial post-contrast T1-WI (c and d) in a patient with MS show unilateral perineural enhancement. Dotted lines (d) depict perineural enhancement in the axial plane.
Anatomical segment involvedIn total, 48 nerves showed intraorbital involvement (63% of MS, 89% of NMO and 90% of MOGAD cases; p = 0.051); 33 showed canalicular (43% of MS, 33% of NMO and 75% of MOGAD cases; p = 0.039) and 23 intracranial involvement (26% of MS, 33% of NMO and 55% of MOGAD cases; p = 0.087). Chiasmatic involvement was observed in 3 patients (3% of MS, 11% of NMO and 5% of MOGAD cases; p = 0.398).
Number of segments involvedThirty-six nerves showed single segment involvement (74% of MS, 56% of NMO and 25% of MOGAD cases), 14 showed 2 segments involved (17% of MS, 22% of NMO and 30% of MOGAD cases), 13 nerves showed 3 segments involved (9% of MS, 22% of NMO and 40% of MOGAD cases) and only one nerve (MOGAD case) showed involvement of all 4 segments (p = 0.006).
In summary, bilateral involvement was observed in eight patients and was statistically significant for diagnosis of MOGAD, whereas unilateral involvement was more prevalent in MS and NMO patients. In addition, intraorbital involvement was seen more frequently in NMO and MOGAD patients, while canalicular involvement was statistically significant for diagnosis of MOGAD. MS patients showed shorter optic nerve involvement (74% of patients had one segment involved), whereas MOGAD showed more extensive lesions (75% showed 2 or more segments involved). NMO had a relatively even distribution among the number of involved segments. We found no statistically significant difference between groups regarding perineural enhancement.
DiscussionThe visual pathway is a common target for MS and antibody-mediated disorders such as NMO and MOGAD. Furthermore, contrast enhancement in an involved optic nerve segment on MRI suggests presence of acute inflammation and is considered a valuable finding contributing to ON diagnosis. We retrospectively analyzed 56 selected patients with clinical diagnosis of MS, NMO or MOGAD who presented at our institution with acute ON and underwent MRI, including optic nerve protocol. Although the latter routinely includes axial and coronal FS T2-WI at our institution, on this occasion optic nerve involvement was assessed based on post-contrast FS T1-WI enhancement exclusively, since high signal intensity on FS T2-WI may, in some cases, reflect residual damage to the optic nerve from a prior episode, or from chronic ON.
In line with previous studies,9,1 we found MOGAD patients were more likely to show bilateral and preferentially intraorbital involvement, 8 suggesting MRI patterns may help distinguish MOGAD cases with bilateral anterior involvement, from both individuals with MS who in general show shorter, unilateral intraorbital lesions; as well as from patients with NMO who tend to present more posterior nerve segment involvement. 16
As reported by other authors, we observed an association between bilateral simultaneous ON and presence of anti-MOG antibodies,13,19 and found bilateral enhancement to be more frequent in MOGAD patients (p = 0.002). However, it is worth noting that some MS and NMO patients also presented bilateral ON in our study, suggesting bilateral optic nerve enhancement presence warrants consideration of MOG antibodies assay. In our cohort, most patients with MS and NMO diagnosis showed unilateral ON. As already mentioned, unilateral ON in MS and bilateral ON in NMO are well established in the literature. This discrepancy may be due to the small number of patients with NMO in our cohort.
Intraorbital segment enhancement was found to be more frequent in NMO and MOGAD patients (p = 0.051), whereas MS patients did not show significant differences between anatomical segments involved. MOGAD patients also had more frequent canalicular involvement than the other groups. Our results confirm previously published evidence in relation to the predominantly anterior nerve involvement observed in MOGAD patients.9,18 In contrast to other authors however,9,20,21 we did not find more posterior segment involvement in our NMO patient cohort, and chiasmatic involvement was distributed equally between all three groups. These results are similar to those of recent studies,22,23 but different from those published by Ramanathan et al., 9 who found statistically significant differences in chiasmatic involvement in NMO patients, a discrepancy possibly due to the limited number of cases with chiasmatic ON in this series.
Prior studies he reported perineural optic nerve enhancement was suggestive of ON due to MOGAD; a finding present in 33–50% of patients.12,14,15 In this study, not only did we not observe statistically significant differences between groups with respect to perineural enhancement, but we found it was also present in both patients with NMO and MS. To the best of our knowledge, this study is the first to he observed perineural enhancement in patients with ON due to MS and NMO.
Extensive longitudinal inflammation of the optic nerve is considered a feature typically seen in MOGAD and NMO patients,9,21,22,24 in the latter, characteristically affecting the chiasmatic segment. Conversely, MS patients usually he less extensive optic nerve involvement. 9 Other studies, however, reported no differences in the number or length of involved segments.8,23 In keeping with previous studies, MS patients in our study showed shorter lesion extent whereas MOGAD showed more longitudinal lesions with two or more segments involved in 75% of the patients. NMO patients analyzed had a relatively even distribution in regard to the extent of the lesions.
The strength of our study is that we only included patients with confirmed diagnosis, and high-quality dedicated orbital MRI, acquired relatively early during acute phases of ON. However, the current study has several limitations. First, its retrospective nature can he sampling bias. Other limitations to consider include the small sample size originating from a single institution, the fact that only 7 patients were under 18 years of age, and finally that AQP4-IgG status was not ailable for the NMO group. Additionally, since we focused on optic nerve involvement, brain and spinal cord findings were not included in the analysis. Lack of certainty in the ailable population proportion data for the selected entities, precluded sample size calculation.
High-dose intrenous corticosteroids are the initial treatment of choice in all demyelinating entities during acute phases of ON, hastening early visual recovery, even if they do not change long-term visual outcome.1,25,26 Although first line treatment is indistinct among the three disorders, 25 patient treatment response, prognosis and further management differ considerably. Hence, patterns of optic nerve involvement on MRI could help distinguish between these conditions, improving initial management and tailoring of specific therapeutic strategies.
Traditionally, brain MRI was the only workup imaging study required to stratify risk for conversion to MS in patients with ON. More recently however, many studies he described distinct MRI patterns of optic nerve involvement in the setting of acute ON, and currently, a dedicated orbital MRI should be included in the diagnostic approach. Nevertheless, MRI pattern distinction is not absolute and overlap features may occur. The difficulty in completely distinguishing between these demyelinating entities based solely on optic nerve enhancement patterns, warrants use of additional brain and spinal cord imaging studies in the appropriate clinical setting.
ConclusionsOur study demonstrates that distinct MRI patterns of enhancement in acute ON may help distinguishing among demyelinating conditions. MOGAD patients are more likely to present bilateral and longitudinally extensive lesions with preferentially anterior visual pathway involvement whereas MS patients he shorter and unilateral nerve involvement.
FootnotesThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.
ORCID iDsMaximiliano Darakdjian https://orcid.org/0000-0002-3336-4092
Hernan Ches https://orcid.org/0000-0001-8649-6374
Jairo Hernandez https://orcid.org/0000-0003-2760-5651
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