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. 2020 Dec 28:jnnp-2020-325121.
doi: 10.1136/jnnp-2020-325121. Online ahead of print.

Brainstem and cerebellar involvement in MOG-IgG-associated disorder versus aquaporin-4-IgG and MS

Samantha A Banks  1 , Padraig P Morris  2 , John J Chen  1   3 , Sean J Pittock  1   4 , Elia Sechi  1   5 , Amy Kunchok  1   6 , Jan-Mendelt Tillema  1 , James P Fryer  4 , Brian G Weinshenker  1 , Karl N Krecke  2 , A Sebastian Lopez-Chiriboga  7 , Adam Nguyen  4 , Tammy M Greenwood  4 , Claudia F Lucchinetti  1 , Nicholas L Zalewski  8 , Steven A Messina  2 , Eoin P Flanagan  9   4
Affiliations

Brainstem and cerebellar involvement in MOG-IgG-associated disorder versus aquaporin-4-IgG and MS

Samantha A Banks et al. J Neurol Neurosurg Psychiatry. .

Abstract

Objective: To determine the frequency and characteristics of brainstem or cerebellar involvement in myelin-oligodendrocyte-glycoprotein-antibody-associated-disorder (MOGAD) versus aquaporin-4-IgG-seropositive-neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD) and multiple sclerosis (MS).

Methods: In this observational study, we retrospectively identified 185 Mayo Clinic MOGAD patients with: (1) characteristic MOGAD phenotype, (2) MOG-IgG seropositivity by live cell-based assay and (3) MRI lesion(s) of brainstem, cerebellum or both. We compared the symptomatic attacks to AQP4-IgG-NMOSD (n=30) and MS (n=30).

Results: Brainstem or cerebellar involvement occurred in 62/185 (34%) MOGAD patients of which 39/62 (63%) were symptomatic. Ataxia (45%) and diplopia (26%) were common manifestations. The median age in years (range) in MOGAD of 24 (2-65) was younger than MS at 36 (16-65; p=0.046) and AQP4-IgG-NMOSD at 45 (6-72; p=0.006). Isolated attacks involving the brainstem, cerebellum or both were less frequent in MOGAD (9/39 (23%)) than MS (22/30 (73%); p<0.001) but not significantly different from AQP4-IgG-NMOSD (14/30 (47%); p=0.07). Diffuse middle cerebellar peduncle MRI-lesions favoured MOGAD (17/37 (46%)) over MS (3/30 (10%); p=0.001) and AQP4-IgG-NMOSD (3/30 (10%); p=0.001). Diffuse medulla, pons or midbrain MRI lesions occasionally occurred in MOGAD and AQP4-IgG-NMOSD but never in MS. Cerebrospinal fluid (CSF) oligoclonal bands were rare in MOGAD (5/30 (17%)) and AQP4-IgG-NMOSD (2/22 (9%); p=0.68) but common in MS (18/22 (82%); p<0.001). Disability at nadir or recovery did not differ between the groups.

Conclusion: Involvement of the brainstem, cerebellum or both is common in MOGAD but usually occurs as a component of a multifocal central nervous system attack rather than in isolation. We identified clinical, CSF and MRI attributes that can help discriminate MOGAD from AQP4-IgG-NMOSD and MS.

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Conflict of interest statement

Competing interests: SAB: Reports no disclosures PPM: Reports no disclosures. JJC: Reports no disclosures. SJP: Reports grants, personal fees and non-financial support from Alexion Pharmaceuticals; grants from Grifols, Autoimmune Encephalitis Alliance; grants, personal fees, non-financial support and other from MedImmune; SJP has a patent # 9,891,219 (Application#12-573942) 'Methods for Treating Neuromyelitis Optica (NMO) by Administration of Eculizumab to an individual that is Aquaporin-4 (AQP4)-IgG Autoantibody positive'. SJP also has patents pending for the following IgGs as biomarkers of autoimmune neurological disorders (septin-5, Kelch-like protein 11, GFAP, PDE10A and MAP1B ES: Reports no disclosures. AK: Reports no disclosures J-MT: Reports no disclosures. JPF: Reports no disclosures. BGW: Receives royalties from RSR, Oxford University, Hospices Civil de Lyon, and MVZ Labor PD Dr Volkmann und Kollegen GbR for a patent of NMO-IgG as a diagnostic test for neuromyelitis optica spectrum disorders, served on adjudication committee for clinical trials in neuromyelitis optica spectrum disorders being conducted by MedImmune/VielaBio and Alexion, and consulted for Chugai/Roche/Genentech and Mitsubishi-Tanabe regarding clinical trials for neuromyelitis optica spectrum disorders. KNK: Reports no disclosures ASL-C: Reports no disclosures. AN: Reports no disclosures TMG: Reports no disclosures. CL: Reports no disclosures SAM: Reports no disclosures. EPF: EPF is a site principal investigator in a randomiSed placebo-controlled clinical trial of Inebilizumab (A CD19 inhibitor) in neuromyelitis optica spectrum disorders funded by MedImmune/Viela Bio.

Figures

Figure 1.
Figure 1.. Representative examples of MRI findings in MOGAD brainstem and cerebellar lesions.
A: An adult patient with an axial T2 FLAIR hyperintense lesion (A, arrow) involving the ventral medulla. B: An adult patient with axial T2 FLAIR hyperintense lesions (B, arrows) involving the left middle cerebellar peduncle, dentate nucleus and cerebellar hemisphere, and the right dentate nucleus with mild mass effect on the left side of the fourth ventricle. C: A pediatric patient with a diffuse pontine T2 FLAIR hyperintense lesion (C, arrow). D: An adult patient with an asymptomatic T2 FLAIR hyperintense lesion involving the right cerebral peduncle (D, arrow). Key: FLAIR, fluid-attenuated inversion recovery; MOGAD, myelin oligodendrocyte glycoprotein antibody associated disorder.
Figure 2.
Figure 2.. Comparison of representative brainstem lesions in MOGAD, AQP4-IgG-NMOSD, and MS.
A: An adult patient with MOGAD has a large lesion of the medulla on axial T2 FLAIR (A1, arrow) with associated enhancement on post-gadolinium T1-weighted images (A2, arrow). An adult patient with MOGAD has T2-hyperintense lesions involving bilateral middle cerebellar peduncles diffusely and extending into the cerebellar parenchyma and pons on axial T2 FLAIR images (A3, arrows). A pediatric patient with MOGAD has a midbrain hyperintense lesion diffusely involving both cerebral peduncles on axial T2 FLAIR images (A4, arrows). B: An AQP4-IgG-NMOSD patient has a hyperintense lesion involving the area postrema region of the dorsal medulla on axial T2 FLAIR images (B1, arrow) with associated gadolinium enhancement on T1 images (B2, arrow). An AQP4-IgG-NMOSD pediatric patient has a hyperintense pontine lesion involving the dorsal pons adjacent to the fourth ventricle on T2 FLAIR images (B3, arrow). An AQP4-IgG-NMOSD adult has a hyperintense midbrain lesion involving the right cerebral peduncle on axial T2 FLAIR images (B4, arrow). C: An adult patients with MS associated axial T2 FLAIR hyperintense brainstem hyperintense lesion involving the right posterior-lateral medulla (C1, arrow) with associated enhancement on axial T1-weighted sequences post-gadolinium (C2, arrow). An adult MS patient with a hyperintense lesion involving the medial cerebellum and superior cerebellar peduncle on axial T2-FLAIR images (C3, arrow). An adult MS patient with a hyperintense lesion in the peripheral midbrain on axial T2-FLAIR images (C4, arrow). Key: AQP4-IgG-NMOSD, aquaporin-4-IgG positive neuromyelitis optica spectrum disorder; FLAIR, fluid-attenuated inversion recovery, MOGAD, myelin oligodendrocyte glycoprotein antibody associated disorder; MS, multiple sclerosis.
Figure 3.
Figure 3.. Evolution of brainstem lesions in MOGAD, AQP4-IgG-NMOSD, and MS.
A: A MOGAD pediatric patient had a diffuse T2 FLAIR hyperintense pontine lesion on axial images (A1, arrow) that completely resolved at 6 month follow up (A2). B: An AQP4-IgG-NMOSD seropositive adult patient had a T2 FLAIR hyperintense dorsal pontine lesion on axial images (B1, arrow) that partially resolved at 9 months follow-up (B2, arrow). C: An adult patient with MS had a hyperintense lateral pontine lesion on axial T2 FLAIR images (C1, arrow) that persisted at 11 months follow up (C2, arrow). Key: AQP4-IgG-NMOSD, aquaporin-4-IgG positive neuromyelitis optica spectrum disorder; FLAIR, fluid-attenuated inversion recovery, MOGAD, myelin oligodendrocyte glycoprotein antibody associated disorder; MS, multiple sclerosis.
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