The Mayo Clinic Neuroimmunology Laboratory
Dr. John Chen, Dr. Sean Pittock and Dr. Eoin Flanagan have provided a list of Mayo Clinic publications from 2018 to the present including commentary in their words on the research. These articles are provided with permission from The Mayo Clinic Neuroimmunology Laboratory.
We studied the long-term clinical outcomes in 29 patients with myelin oligodendrocyte glycoprotein (MOG) antibody associated disorders (MOGAD with follow up of 9 years or more. The median follow-up duration was 14 years (range, 9-31). The median EDSS at last follow-up was 2 (range, 0-10) which is consistent with mild disability. Patients did develop additional mild disability with subsequent attacks, supporting the rationale for studies of attack prevention treatments in MOGAD. No patients had a secondary progressive disease course. In summary, we found most MOGAD patients had a favorable long-term outcome without secondary progression despite frequent relapses. This differs from the outcome reported with MS and aquaporin-4-IgG neuromyelitis optica spectrum disorders (NMOSD).
This study looked at the population-based etiologies of optic neuritis using the Rochester Epidemiology Project. 5% of optic neuritis was caused by MOGAD in the predominantly white population of Olmsted County, MN. Other causes of optic neuritis were multiple sclerosis in 57%, idiopathic in 29%, and AQP4-IgG positive NMOSD in 3%.
This study reports two patients with multiple relapses and poor outcome with MOGAD and highlights some of the MRI findings of brain thinning.
The 2015 diagnostic criteria for NMOSD was created before the appreciation of MOGAD as a distinct disorder. This study looked at 170 MOGAD patients seen at the Mayo Clinic and found that only 43 (25%) fulfilled the 2015 seronegative NMOSD criteria. This highlights that the NMOSD criteria fails to capture the majority of MOGAD patients and supports specific molecular biomarker-associated diagnostic criteria for inflammatory central nervous system disorders.
In this study, Mayo Clinic investigators showed that organ specific autoimmunity is much less common with MOG-IgG versus AQP4-IgG positive NMOSD and highlights further the difference between these disorders.
This study is the largest human pathological study of MOGAD that was done as a collaboration between Mayo Clinic and The University of Vienna. We defined the histopathology of 22 biopsies and 2 autopsies from patients with myelin oligodendrocyte glycoprotein (MOG) antibody associated disorders (MOGAD). MOGAD pathology is dominated by coexistence of both perivenous and confluent white matter demyelination, with an over-representation of intracortical demyelinated lesions compared to typical MS. Radially expanding confluent slowly expanding smoldering lesions in the white matter as seen in MS, are not present. A CD4+ T-cell dominated inflammatory reaction with granulocytic infiltration predominates. Complement deposition is present in all active white matter lesions, but a preferential loss of MOG is not observed. AQP4 is preserved. MOGAD is pathologically distinguished from AQP4-IgG seropositive NMOSD, but shares some overlapping features with MS. The results may have implications for future development of treatments in MOGAD.
In this study Mayo Clinic investigators showed that in up to 10% of patients with MOG-IgG myelitis, the initial MRI can be negative. Thus, a negative MRI spine should not dissuade from MOG-IgG testing in a patient with acute/subacute myelitis.
In this multicenter study of MOG-IgG cell-based assays (CBAs) involving Mayo Clinic and other international investigators, live MOG-IgG CBAs showed excellent agreement for high positive and negative samples at 3 international testing centers. Low positive samples were more frequently discordant than in a similar comparison of aquaporin-4 antibody assays. Further research is needed to improve international standardization for clinical care.
This study evaluated the frequency of having both MOG-IgG and AQP4-IgG positive in the same patient. Among 15,598 patients tested for both MOG-IgG and AQP4-IgG, only 10 patients (0.06%) were positive for both. When both were positive, the AQP4-IgG titers were typically much higher than the MOG-IgG and the clinical phenotype resembled AQP4-IgG positive NMOSD more than MOGAD. This study demonstrates that co-positivity of both AQP4-IgG and MOG-IgG is quite rare.
This study retrospectively reviewed 173 MOGAD patients and found that 18 (10%) had symptoms of area postrema syndrome (intractable nausea, vomiting, and/or hiccups) that were typically in conjunction with other neurologic symptoms. Only 1 (0.6%) MOGAD patient had isolated symptoms of area postrema syndrome, which is much less common than seen in AQP4-IgG positive NMOSD (9.4%–14.5%).
In this study, Mayo Clinic investigators report two patients with MOG-IgG antibody associated disorder who had unilateral hemi-encephalitis, a recently recognize syndrome associated with this antibody.
MOGAD often causes optic neuritis with perineural enhancement (inflammation of the optic nerve sheath and peribulbar fat). This study reported 2 MOGAD patients that had optic perineuritis (inflammation of the optic nerve sheath) with sparing of the optic nerve. Because MOGAD has a propensity to involve the optic nerve sheath, it is possible that many previous cases of “idiopathic” optic perineuritis may be explained by MOGAD.
In this international collaborative study including Mayo Clinic investigators this study showed that the live cell based MOG-IgG assay used at Mayo Clinic and Oxford was superior to the fixed cell based assay. An accompanying editorial highlighted the live-cell based assay, used at Mayo Clinic as being the gold standard for detecting MOG-IgG.
In this observational study of 54 patients with MOG-IgG myelitis, we showed it may mimic viral/post viral acute flaccid myelitis. Longitudinally extensive T2-hyperintense lesions are typical, but most patients have more than 1 lesion, and an H-shaped axial T2 pattern confined to gray matter and lack of enhancement are discriminating features from aquaporin-4–IgG and MS myelitis. Myelitis attacks are more severe than MS but recover better than AQP4-IgG positive neuromyelitis optica spectrum disorder. Recognition of the clinical and radiologic characteristics of MOG-IgG myelitis and its discriminators from other etiologies will help clinicians identify patients with myelitis in whom MOG-IgG should be tested.
In this study, Mayo Clinic investigators showed that the availability of MOG-IgG and Aquaporin-4-IgG allowed 12-14% of cases of transverse myelitis previously labelled idiopathic to be given a specific diagnosis. This highlighted the need to incorporate these biomarkers into future transverse myelitis diagnostic criteria.
In this collaborative study between Mayo Clinic Investigators and Sri Lanka, MOG-IgG was found in 17% of patients with inflammatory demyelinating diseases of the CNS and 3.5 times more common than AQP4-IgG.
This is one of the largest published cohorts of patients with MOG-IgG associated disorder (MOGAD) optic neuritis. The study showed that MOGAD optic neuritis typically presents with severe vision loss, but recovery is much better than AQP4-IgG positive neuromyelitis optica spectrum disorder (NMOSD) optic neuritis. Features of MOGAD optic neuritis are optic disc edema at onset (up to 86%), bilateral (50%), recurrent (50%), and perineural enhancement on MRI (50%).
- Laboratory findingb: serum positive for MOG-IgG by cell-based assayc
- Clinical findings: any of the following presentations:
- Optic neuritis, including CRION
- Transverse myelitis (ie, LETM or STM)
- Brain or brainstem syndrome compatible with demyelination
- Any combination of the above
- Exclusion of alternative diagnosis
Abbreviations: ADEM, acute demyelinating encephalomyelitis; CRION, chronic relapsing inflammatory optic neuropathy; LETM, longitudinally extensive transverse myelitis; STM, short-segment transverse myelitis.
a Must meet all 3 criteria.
b Transient seropositivity favors lower likelihood of relapse.
c In absence of serum, positivity in cerebrospinal fluid would allow fulfillment of criteria 1.
This study looked at a large cohort patients with recurrent optic neuritis and found that 13% were caused by MOGAD, 19% were caused by AQP4-IgG NMOSD, 19% were caused by multiple sclerosis, and 49% were “double negative” (cause is unknown). MOGAD patients had frequent relapses, but retained good vision compared to AQP4-IgG NMOSD.
This study evaluated serum from 177 participants from the Optic Neuritis Treatment Trial that was completed in 1991 and found 3 (1.7%) were positive for MOG-IgG and no patients were positive for AQP4-IgG. This low percentage of positivity was likely due to the inclusion criteria of the trial, which excluded patients with prior optic neuritis and bilateral optic neuritis. Two of the three MOGAD patients had a relapse of optic neuritis in the 15 year follow-up period. All 3 retained good visual acuity.
The following are review articles on MOGAD, which discuss how MOGAD differs from other demyelinating conditions, such as neuromyelitis optica spectrum disorder:
Chen, John J., et al. “Optic neuritis in the era of biomarkers.” Survey of Ophthalmology 65.1 (2020): 12-17.
Chen, John J., and M. Tariq Bhatti. “Clinical phenotype, radiological features, and treatment of myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) optic neuritis.” Current Opinion in neurology 33.1 (2020): 47-54.
Prasad, Sashank, and John Chen. “What you need to know about AQP4, MOG, and NMOSD.” Seminars in neurology. Vol. 39. No. 06. Thieme Medical Publishers, 2019.
Tajfirouz, Deena A., M. Tariq Bhatti, and John J. Chen. “Clinical Characteristics and Treatment of MOG-IgG–Associated Optic Neuritis.” Current neurology and neuroscience reports 19.12 (2019): 100.
Chen, John J., and Clare L. Fraser. “Do myelin oligodendrocyte glycoprotein antibodies represent a distinct syndrome?.” Journal of Neuro-Ophthalmology 39.3 (2019): 416-423.
Flanagan, Eoin P. “Neuromyelitis optica spectrum disorder and other non–multiple sclerosis central nervous system inflammatory diseases.” CONTINUUM: Lifelong Learning in Neurology 25.3 (2019): 815-844.
NOTE: This article is available through purchase, but may be requested.