Table 2.
Overlapping MOGAD/positive MOG-IgG and AQP4-IgG + NMOSD.
| References | Number of cases | Sex/age | Clinical phenotype or laboratory status | Antibody testing assay, source
(serum/CSF), notable clinical features, or MRI findings |
|---|---|---|---|---|
| Mader et al. (2011)67 | 1 | F/39 | NMOSD | AQP4-IgG: live CBA, NA MOG-IgG: live CBA, NA NMOSD with 4 relapses of ON, TM, LETM, and no MRI cerebral lesions. |
| Kezuka et al. (2012)68 | 6 | F/48 F/35 F/41 F/50 F/21 F/48 |
Unilateral or bilateral retrobulbar neuritis | AQP4-IgG: live CBA, serum MOG-IgG: ELISA, serum |
| Xu et al. (2012)69 | 1 | F/60 | NMOSD | AQP4-IgG: NA, serum MOG-IgG: NA, serum Multiple episodes of thoracic TM, ON with T2-hyperintense spinal cord lesion in T6-T9 and no typical MS lesions in the brain, initially misdiagnosed as MS and treated with IFNβ-1a, further found to be double positive for AQP-IgG and MOG-IgG. |
| Woodhall et al. (2013)70 | 1 | F/34 | NMOSD | AQP4-IgG: live CBA, serum MOG-IgG: live CBA, serum MOG-IgG and AQP4-IgG double-positive patients had significant disabilities. She had eight attacks over the disease duration of 12 years, EDSS = 9, progression index = 0.8, and no history of simultaneous ON + TM. |
| Cavus et al. (2013)71 | 1 | NA/NA | NMOSD | AQP4-IgG: CBA, serum MOG-IgG: CBA, serum GlyR-IgG: CBA, serum Patients with simultaneous ON and TM were more prone to have antibodies against the Glycine receptor. |
| Martinez-Hernandez et al. (2014)72 | 2 | NA/NA | NMOSD | AQP4-IgG: CBA, serum MOG-IgG: CBA, serum |
| Waters et al. (2015)73 | 11 | NA/NA | Non-MS CNS demyelinating disease | AQP4-IgG: CBA, serum MOG-IgG: CBA, serum, using either full-length (FL-MOG) or the short-length (SL-MOG) human MOG-Ab. The SL-MOG assay detected Abs in 1 patient (low positive SL-MOG), who was strongly positive for AQP4-IgG. |
| Sepúlveda et al. (2015)74 | 2 | NA/NA | NMOSD | AQP4-IgG: CBA, serum MOG-IgG: CBA, serum |
| Matsuda et al. (2015)75 | 2 | F/41 F/48 |
NMOSD | AQP4-IgG: CBA IIF, serum MOG-IgG: CBA, serum From MOG-IgG-positive patients, 2 were AQP4-IgG-positive BON (NMO), of which one had 4 relapses with vision improvement after treatment with residual visual field deficit. The other one had eight relapses, no vision improvement after treatment, and residual visual field deficit. |
| Hoftberger et al. (2015)76 | 2 | F/58 F/50 |
NMOSD | AQP4-IgG: CBA IIF, serum MOG-IgG: CBA, serum Patients with both antibodies presented with a classic NMO clinical picture of simultaneous BON and LETM. |
| Di Pauli et al. (2015)77 | 1 | M/71 | MOG-EMwith double positive AQP4-IgG and MOG-IgG | AQP4-IgG: Live CBA IIF, serum (AQP4 antibodies were absent at
disease onset but seroconverted to low-titer positive at week
nine with a titer of 1:40) MOG-IgG: Live CBA IIF, serum Presentation of MOG-EM with predominant optic and spinal involvement (acute visual and gait disturbance that dramatically worsened to bilateral amaurosis, tetraplegia, and respiratory insufficiency within a few days). MRI showed multiple supra- and infratentorial lesions with marked diffusion restriction, only slight hyperintensity on T2-W images, and intramedullary lesions (lesions marginally enhanced contrast). |
| Yan et al. (2016)78 | 10 | F (N = 10)/median age at first attack: 32 (age range 15–60) | NMOSD | AQP4-IgG: FACS-based cell-binding assay, serum MOG-IgG: FACS-based cell-binding assay, serum The double-positive patients had a multiphase disease course with a high annual relapse rate, and severe residual disability compared to patients with only MOG-IgG. Of the double-positive patients, 70% had MS-like brain lesions, more severe edematous, multifocal regions on spinal MRI, pronounced decreases of retinal nerve fiber layer thickness and atrophy of optic nerves. 80% of double-positive patients had clinical evidence of spinal cord involvement at the first attack of NMOSD. The conus was significantly more likely to be involved in the double-positive group and MOG-IgG-positive patients. |
| Idiman et al. (2017)79 | 5 | NA/NA | NMOSD with atypic aggressive demyelinating disease | AQP4-IgG: CBA, serum MOG-IgG: CBA, serum |
| Vural et al. (2017)80 | 2 | NA/NA | NMOSD with positive MOG-IgG and MOG-IgM | AQP-IgG: NA, NA MOG-IgG: CBA and flow cytometry, serum |
| Yang et al. (201881 | 1 | F/41 | GFAP astrocytopathy with double positive AQP4-IgG and MOG-IgG | AQP4-IgG: IIF, CSF MOG-IgG: IIF, serum Presented with SIADH and fever, vertigo, quadriplegia, dementia, and psychosis. Brain MRI showed lesions in bilateral thalamus, right hypothalamus and midbrain, left hippocampus, right parietal, frontal lobe, and T1-W “radial enhancing” lesions in the cerebellum. Spinal cord MRI was normal. |
| Kunchok et al. (2019)25 | 6 | NA/NA | CNS inflammatory demyelinating disorders | AQP4-IgG: live CBA, serum MOG-IgG: live CBA, serum All double-positive cases had high titer AQP4-IgG and low titer MOG-IgG. |
| Kunchok et al. (2020)82 | 10 | F (N = 9) M (N = 1)/median age: 47 (age range: 30–61 years) |
CNS inflammatory demyelinating disorders | AQP4-IgG: flow cytometric assay, serum MOG-IgG: flow cytometric assay, serum All 10 patients with dual positivity had high-titer AQP4-IgG (median, 1:10 000; range, 1:100 to 1:100 000) and low-titer MOG-IgG (median, 1:40; range, 1:20 to 1:100). |
| Ishikawa et al. (2019)83 | 1 | F/24 | Unilateral or bilateral optic neuritis | AQP4-IgG: IIF, serum MOG-IgG: CBA, serum Presented with right ON at age 13, followed by left ON at age 18 (positive AQP4-IgG), and left ON at age 22 (positive MOG-IgG). |
| Bates et al. (2020)84 | 1 | F/54 | Myasthenia gravis (MG) with double-positive AQP4-IgG and MOG-IgG | AQP4-IgG: CBA, NA MOG-IgG: CBA, NA Presentation of acute right-sided weakness in a patient with long-standing MG.MRI showed longitudinally extensive edema beginning at the level of T1-T2 and extending up into the obex and area postrema with associated contrast enhancement of levels C1-C4. |
| Mori et al. (2020)85 | 1 | F/NA | NMOSD | AQP4-IgG: NA MOG-IgG: NA Presentation of two episodes of right ON and two episodes of left ON resulting in severe visual function disability. |
| He et al. (2020)86 | 1 | NA | NMOSD | AQP4-IgG: ELISA or IIFT, NA MOG-IgG: IIFT, NA |
| Zhang et al. (2021)87 | 1 | F/79 months | NMOSD | AQP4-IgG: commercial kit, serum (assay not
specified) MOG-IgG: commercial kit, serum (assay not specified) |
| Mason et al. (2021)88 | 1 | F/66 | Isolated sequential bilateral optic neuritis | AQP4-IgG: NA, serum MOG-IgG: NA, serum MRI of the brain and orbits revealed enhancement of the left optic nerve with no cerebral WM plaques. |
Abbreviations: NMOSD: neuromyelitis optica spectrum disorder; CBA: cell-based assay; ON: optic neuritis, TM: transverse myelitis; LETM: longitudinally extensive transverse myelitis; MRI: magnetic resonance imaging; ELISA: enzyme-linked immunosorbent assay; MS: multiple sclerosis; EDSS: expanded disability status scale; GlyR-Ab: glycine receptor antibody; FL-MOG: full-length human MOG-Ab; SL-MOG: short-length human MOG-Ab; BON: bilateral optic neuritis; EM: encephalomyelitis; FACS: fluorescence-activated cell sorting; IIF: indirect immunofluorescence; MG: myasthenia gravis.