Highlights
- •Opticospinal multiple sclerosis (OSMS) is a rare MS phenotype identified in Asian and non-Asian populations.
- •OSMS is an immune-mediated disease characterized by selective involvement of the optic nerve and spinal cord, with spinal cord lesions affecting fewer than three vertebral segments, and absence of AQP4 and MOG antibodies.
- •Optic neuritis in OSMS has an excellent long term prognosis regarding visual function despite the high number of recurrences and significant structural damage.
- •Determination of peripapillary retinal nerve fiber layer and macular ganglion cell and inner plexiform layer atrophy, and inter-eye percentage and absolute difference accurately separated patients with unilateral optic neuritis from healthy controls.
Abstract
Background
Biomarkers have improved the classification of autoimmune inflammatory disorders,
including optic neuritis (ON) as a frequent presentation of multiple sclerosis, neuromyelitis
spectrum disorders, MOG antibody-related disease (MOGAD), and opticospinal multiple
sclerosis (OSMS). The phenotype of OSMS in non-Asian populations is less well known.
Objective
We investigated the clinical features and prognosis of OSMS–ON in a Brazilian cohort.
Methods
This was a single-center cohort study of patients from Rio de Janeiro (Brazil) with
OSMS. All individuals were MOG- and AQP4-seronegative, clinically diagnosed with ON,
and had magnetic resonance imaging-confirmed transverse myelitis (TM). Subjects and
healthy controls (HCs) were assessed for visual acuity (logMAR VA), automated perimetry
mean deviation (MD), intraocular pressure, and spectral-domain optical coherence tomography
(OCT), followed by automated retinal layer segmentation of the peripapillary retinal
nerve fiber layer (pRNFL) and macular ganglion cell and inner plexiform layer (mGCIPL).
Receiver operator characteristic curves were plotted and the area under the curve
(AUC) was calculated for group comparisons of retinal asymmetry of the pRNFL and mGCIPL.
Results
The 30 patients with OSMS were predominantly female and white. The mean age was 48
years (range 20–70 years). Unilateral ON was the index event in 83.3% of patients.
Over the average 18-year follow-up period, there were 89 relapses of ON. In individuals
with OSMS, the average VA was 0.07±0.14 in the right eye (RE) and 0.13±0.30 in the
left eye (LE). The MD was −5.37±5.88 dB and −5.23±3.34 dB for the RE and LE, respectively.
There was a significant cumulative loss of VA (p = 0.0003) and MD (p = 0.0001) with a higher number of recurrent episodes. Atrophy of the pRNFL thickness
was significant in OSMS (RE, 78.62 ± 16.01 µm; LE, 79.86 ± 13.79 µm) relative to the
HC group (RE, 98.87 ± 10.68 µm; LE, 97.87 ± 10.85 µm, p = 0.0001). Likewise, there was significant mGCIPL atrophy in patients with OSMS (RE,
74.96 ± 14.46 µm; LE, 73.88 ± 13.79 µm) relative to the HC group (RE, 90.50 ± 6.74 µm;
LE, 90.41± 6.89 µm; p = 0.0001). Retinal asymmetry, inter-eye percentage, and absolute differences accurately
separated patients with unilateral ON from HCs (AUC=0.89 and AUC=0.85, respectively).
Conclusion
A structural-functional paradox was found in OSMS with a high diagnostic value for
a novel metric based on retinal asymmetry. The functional visual outcome are excellent
despite significant structural damage to the inner retinal layers in patients with
a high ON relapse rate and long-term bilateral sequential involvement.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Multiple Sclerosis and Related DisordersAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Temporal visual resolution and disease severity in MS.Neurol. Neuroimmunol. Neuroinflamm. 2018; 5: 492
- Bilateral and recurrent optic neuritis in multiple sclerosis.Acta Neurol. Scand. 2011; 123: 207-210
- Retinal atrophy in relation to visual functioning and vision-related quality of life in patients with multiple sclerosis.Mult. Scler. 2018; 24: 767-776
- Diagnostic accuracy of optical coherence tomography inter-eye percentage difference for optic neuritis in multiple sclerosis.Eur. J. Neurol. 2017; 24: 1479-1484
- Asymptomatic visual field disturbances in multiple sclerosis patients without a history of optic neuritis.Neurol. Neurochir. Pol. 2007; 41: 223-228
- The relationship between visual field and retinal nerve fiber layer measurements in patients with multiple sclerosis.Invest. Ophthalmol. Vis. Sci. 2007; 48: 5798-5805
- Optic neuritis in the era of biomarkers.Surv. Ophthalmol. 2020; 65: 12-17
- The APOSTEL recommendations for reporting quantitative optical coherence tomography studies.Neurology. 2016; 86: 2303-2309
- Asymptomatic optic nerve lesions: an underestimated cause of silent retinal atrophy in MS.Neurology. 2020; 94: 2468-2478
- MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome.J. Neuroinflamm. 2016; 13: 280
- Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS).Neurology. 1983; 33: 1444-1452
- Quality control functions of the Visual Field Reading Center (VFRC) for the Optic Neuritis Treatment Trial (ONTT).Control. Clin. Trials. 1993; 14: 143-159
- Visual field profile of optic neuritis: a final follow-up report from the optic neuritis treatment trial from baseline through 15 years.Arch. Ophthalmol. 2010; 128: 330-337
- Western versus Asian types of multiple sclerosis: immunogenetically and clinically distinct disorders.Ann. Neurol. 1996; 40: 569-574
- A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis.Lancet. 2004; 364: 2106-2112
- Devic’s neuromyelitis optica: a clinicopathological study of 8 patients.Ann. Neurol. 1993; 34: 162-168
- Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders.J. Neuroinflamm. 2011; 8: 184
- The ocular manifestations of multiple sclerosis. 1. Abnormalities of the afferent visual system.J. Neurol. Neurosurg. Psychiatry. 1992; 55: 747-752
- Two subtypes of optic-spinal form of multiple sclerosis in Japan: clinical and laboratory features.J. Neurol. 2007; 254: 488-492
- Optimal intereye difference thresholds by optical coherence tomography in multiple sclerosis: an international study.Ann. Neurol. 2019; 85: 618-629
- Clinical, CSF, and MRI findings in Devic’s neuromyelitis optica.J. Neurol. Neurosurg. Psychiatry. 1996; 60: 382-387
- The investigation of acute optic neuritis: a review and proposed protocol.Nat. Rev. Neurol. 2014; 10: 447-458
- Retinal asymmetry in multiple sclerosis.Brain. 2021; 144: 224-235
- Is Asian type MS an MS phenotype, an NMO spectrum disorder, or a MOG-IgG related disease?.Mult. Scler. Relat. Disord. 2020; 42102082
- Lower frequency of antibodies to MOG in Brazilian patients with demyelinating diseases: an ethnicity influence?.Mult. Scler. Relat. Disord. 2018; 25: 87-94
- Clinical course of optic neuritis in patients with relapsing neuromyelitis optica.Arch. Ophthalmol. 2008; 126 (Jan): 12-16
- Antibodies to myelin oligodendrocyte glycoprotein are uncommon in Japanese opticospinal multiple sclerosis.Mult. Scler. 2016; 22: 447-458
- Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination.J. Neurol. Neurosurg. Psychiatry. 2018; 89: 127-137
- Anti-aquaporin 4 antibody in selected Japanese multiple sclerosis patients with long spinal cord lesions.Mult. Scler. 2007; 13: 850-855
- The OSCAR-IB consensus criteria for retinal OCT quality assessment.PLoS One. 2012; 7: 1-7
- The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies.J. Clin. Epidemiol. 2008; 61: 344-349
- Recurrent optic neuromyelitis with endocrinopathies: a new syndrome.Neurology. 1997; 48: 58-64
- The clinical course of neuromyelitis optica (Devic’s syndrome).Neurology. 1999; 53: 1107-1114
- Revised diagnostic criteria for neuromyelitis optica.Neurology. 2006; 66: 1485-1489
- The spectrum of neuromyelitis optica.Lancet Neurol. 2007; 6: 805-815
- International consensus diagnostic criteria for neuromyelitis optica spectrum disorders.Neurology. 2015; 85: 177-189
Article info
Publication history
Published online: September 08, 2021
Accepted:
September 6,
2021
Received in revised form:
August 23,
2021
Received:
April 20,
2021
Identification
Copyright
© 2021 Elsevier B.V. All rights reserved.
