Table 1:
Clinical, serological and radiological features of dual-positive MOG-IgG1+/NMDA-R-IgG+ patients
| No/Age^/Sex | MOG-IgG1 titer | Coexistent antibodies# | Timing of antibody detection | Clinical-anatomical phenotype of first attack | Clinical-anatomical phenotype of subsequent attacks | Attac ks (n) | Time to second attack | Enceph alo-pathy | Seizure s | NMDA-R-IgG encephalitis clinical features | ADEM criteria | NMDA-R encephali tis criteria | NMO SD criteri a | CSF OCB (≥4 CSF restrict ed) | MRI |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1/2/M | 1:20a | NMDA-R-IgG IFA+ (no titer) & CBA+ | MOG-IgG1 (1st attack, age 2) NMDA-R-IgG+/MOG-IgG1- (2nd attack age 7) | Multifocal meningoencephalitis (meningeal, cortical, diencephalon involvement) | Multifocal meningoencephalitis (meningeal, cortical, diencephalon involvement), ON, cervical TM | 2 | 5 years | Y | Y | Cognitive and behavioral abnormalities | Y (1st attack) | Y (2nd attack) | N | N | Age 2: T2 hyperintensity in left caudate, left thalamus, left basal ganglia. Diffuse leptomeningeal enhancement and patchy cortical T2/FLAIR hyperintensity. Age 7: Bilateral optic neuritis. Multiple enhancing lesions in supratentorial white matter. Periventricular enhancement right occipital horn. Enhancing lesions-central/dorsal cord C2–3, right hemicord C4, central cord C6–7. |
| 2/6/F | 1:20b | NMDA-R-IgG IFA+(1:64) & CBA+ | NMDA-R-IgG+/MOG-IgG1+ (3rd & 4th attacks) | ON | ON, Multifocal meningoencephalitis (meningeal, cortical, diencephalon involvement), cervical TM | 5 | 4 years | Y | N | Aphasia, agitation, perseveration, mutism, choreoathetoid movements, visual and auditory hallucinations, psychosis (attacks 3–5) | Y (3rd, 4th, 5th attacks) | Y (3rd, 4th, 5th attacks) | N | ND | Age 13: T2 hyperintensity in insular cortex and left frontal operculum. Left frontoparietal unilateral leptomeningeal enhancement. Age 18: Leptomeningeal enhancement of right hemisphere, T2/FLAIR hyperintensity right temporal lobe. Patchy T2 signal in the ventral cord C4-C6 Age 23: T2 hyperintensity in inferior left temporal lobe |
| 3/12/F | 1:1000 | NMDA-R-IgG CBA+ | Simultaneous MOG-IgG1+/NMDA-R-IgG+ (onset) | Encephalitis (diencephalon) | NA | 1 | NA | Y | Y | Choreiform movements, oral dyskinesias and tongue biting | Y (1st attack) | Y (1st attack) | N | NA | Age 12: T2 hyperintensity in the left anterior basal ganglia. |
| 4/14/F | 1:100 | NMDA-R-IgG IFA+ & CBA+ | Simultaneous MOG-IgG1+/NMDA-R-IgG+ (4 weeks from onset) | Multifocal meningoencephalitis | NA | 1 | NA | Y | Y | Aphasia, visual hallucinations, insomnia | Y (1st attack) | Y (1st attack) | N | Y | Age 14: Leptomeningeal and gyral enhancement around splenium corpus and callosum |
| 5/15/F | 1:100 | NMDA-R-IgG CBA+ | NMDA-R-IgG+ at onset, MOG-IgG1+ (8 weeks from onset) | Multifocal meningoencephalitis (meningeal, cortical, diencephalon involvement), ON | Multifocal encephalitis (cortical, diencephalon, brainstem involvement) | 2 | 4 weeks | Y | Y | Combative, agitation | Y (1st attack) | Y (1st attack) | N | N | Age 15: T2 hyperintensity in right hypothalamus, chiasm and right optic tract. Right optic disc enhancement. 2nd attack: T2 hyperintense lesions in the left thalamus, right frontal subcortical and left pons. |
| 6/18/F | 1:1000 | NMDA-R-IgG CBA+ | Simultaneous MOG-IgG1+/NMDA-R-IgG+ (6 weeks from onset) | Multifocal encephalitis with cortical, diencephalic involvement | Multifocal encephalitis with cortical, diencephalic and brainstem involvement | 2 | 6 weeks | Y | N | Gait and truncal ataxia | Y (1st attack) | Y (1st attack) | N | N | Age 18: Gyral swelling in the left parietal region and sulcal FLAIR hyperintensity. 2nd attack: Bilateral T2/FLAIR hyperintensity in deep nuclei and corticospinal tracts, internal capsule and brainstem |
| 7/19/M | 1:40 | NMDA-R-IgG IFA+ (1:8) & CBA+ | Simultaneous MOG-IgG1+/NMDA-R-IgG+ (2nd attack, 13 years from onset) | Multifocal encephalitis with diencephalic involvement | Multifocal encephalitis with diencephalic, brainstem involvement | 2 | 12 years | Y | N | Deja vu, auditory and visual hallucinations | Y (1st and 2nd attack) | Y (2nd attack) | N | Y | Age 19: T2/FLAIR hyperintensities in right periventricular and subcortical white matter Age 31: Punctate and curvilinear enhancement right ventral pons. Punctate lesions in pons and midbrain. T2 hyperintensity and enhancement of posterior limb of internal capsule. |
| 8/27/F | 1:40 | NMDA-R-IgG CBA+ AQP4-IgG CBA+ 1:100 | Simultaneous MOG-IgG1+/NMDA-R-IgG+/AQP4-IgG+ (onset) | Cervical LETM, right optic neuritis | NA | 1 | NA | N | N | NA | N | N | Y | Age 27: T2/FLAIR changes in right temporal lobe, right thalamus, optic tract and chiasm without enhancement. C2-C6 lesion with enhancement. | |
| 9/33/M* | 1:100 | NMDA-R-IgG IFA+ (no titer) & CBA+ | NMDA-R-IgG+ (onset) MOG-IgG1+ (4 weeks from onset) | Multifocal meningoencephalitis (meningeal, cortical, diencephalon involvement) | Multifocal meningoencephalitis, ON, TM | 2 | 3 weeks | Y | Y | Visual and auditory hallucinations, paranoia | Y (1st attack) | Y (1st attack) | N | NA | Age 33: Right temporal lobe enhancement, leptomeningeal enhancement and cortical edema, upper brainstem enhancement. 2nd attack: Enhancing lesions in mesial temporal lobes, subcortical cerebral hemispheres, bilateral middle cerebellar peduncles left cerebellum. Enhancement of the optic nerves and nerve sheaths bilaterally. Small enhancing lesions in the cervical and thoracic spine. |
| 10/33/M | 1:100 | NMDA-R-IgG IFA+ (1:64) & CBA+ GFAP-IgG IFA+ (1:64) & CBA+c | Simultaneous MOG-IgG1+/NMDA-R-IgG+/GFAP-IgG+ (4 months from onset) | Multifocal meningoencephalitis (meningeal, cortical involvement) | Cervical LETM | 2 | 8 weeks | Y | Y | Aphasia | Y (1st attack) | Y (1st attack) | N | N | Age 33: T2 hyperintensity and leptomeningeal enhancement along the left temporal, frontal, parietal and suprasylvian sulci. 2nd attack: T2/FLAIR hyperintensity in the left basal ganglia and the left inferior cerebellar peduncle. Cervical spine T2 hyperintensity and expansion C1-C3 and C6-C7 level with enhancement |
| 11/39/M | 1:100 | NMDA-R-IgG CBA+ (CSF) | Simultaneous MOG-IgG1+/NMDA-R-IgG+ (3 months from onset) | Multifocal meningoencephalitis with leptomeningeal, cortical, diencephalic, brainstem involvement. Left optic neuritis. | NA | 1 | NA | Y | N | Agitation, disinhibition | Y (1st attack) | Y (1st attack) | N | Y | Age 39: Patchy leptomeningeal and cortical enhancement of the brainstem, midbrain, right cerebellar hemisphere, vermis, bilateral temporal and frontal lobes. T2 hyperintensity in cerebellum, brainstem, and supratentorial brain. Multiple enhancing nodules along the anterior and posterior surfaces of the spinal cord. Enhancement of the distal left optic nerve. |
Abbreviations: CBA= cell-based assay, IFA = immunofluorescence assay, ON = optic neuritis, TM = transverse myelitis, LETM = longitudinally extensive transverse myelitis. ND= not done, NA= not applicable or available
^
Age at onset of disease
#
All patients with NMDA-R-IgG positivity were tested in CSF
a
Patient tested positive for MOG-IgG1 twice, 4 years apart. Positive at 1:20, titration not completed.
b
Patient tested positive for MOG-IgG1 at disease onset 1:20, titration not completed. Subsequent serum testing in 5 years from onset was negative for MOG-IgG1.
c
GFAP-IgG positive in CSF
*
Case described by Carroll et al in Practical Neurology: case reports. November/December 2019.