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Original research
Brainstem and cerebellar involvement in MOG-IgG-associated disorder versus aquaporin-4-IgG and MS
  1. Samantha A Banks1,
  2. Padraig P Morris2,
  3. John J Chen1,3,
  4. Sean J Pittock1,4,
  5. Elia Sechi1,5,
  6. Amy Kunchok1,6,
  7. Jan-Mendelt Tillema1,
  8. James P Fryer4,
  9. Brian G Weinshenker1,
  10. Karl N Krecke2,
  11. A Sebastian Lopez-Chiriboga7,
  12. Adam Nguyen4,
  13. Tammy M Greenwood4,
  14. Claudia F Lucchinetti1,
  15. Nicholas L Zalewski8,
  16. Steven A Messina2,
  17. Eoin P Flanagan1,4
  1. 1 Neurology, Mayo Clinic, Rochester, Minnesota, USA
  2. 2 Radiology (Division of Neuroradiology), Mayo Clinic, Rochester, Minnesota, USA
  3. 3 Ophthalmology, Mayo Clinic Rochester, Rochester, Minnesota, USA
  4. 4 Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
  5. 5 Department of Clinical and Experimental Medicine, Sassari University Hospital, Sassari, Sardegna, Italy
  6. 6 Neurology, Cleveland Clinic, Cleveland, Ohio, USA
  7. 7 Neurology, Mayo Clinic, Jacksonville, Florida, USA
  8. 8 Neurology, Mayo Clinic, Scottsdale, Arizona, USA
  1. Correspondence to Dr Eoin P Flanagan, Neurology, Mayo Clinic, Rochester, MN 55905-0002, USA; flanagan.eoin{at}mayo.edu

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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Footnotes

  • Twitter @akunchok

  • Contributors SAB: data acquisition, analysed and interpreted the data, drafting of manuscript PPM: radiographic data review, analysed and interpreted the data, critical revision of manuscript JJC: analysed and interpreted the data, critical revision of manuscript SJP: analysed and interpreted the data, critical revision of manuscript. ES: analysed and interpreted the data, critical revision of manuscript. AK: analysed and interpreted the data, critical revision of manuscript J-MT: analysed and interpreted the data, critical revision of manuscript. JPF: analysed and interpreted the data, critical revision of manuscript. BGW: analysed and interpreted the data, critical revision of manuscript KNK: analysed and interpreted the data, critical revision of manuscript. ASL-C: analysed and interpreted the data, critical revision of manuscript. AN: analysed and interpreted the data, critical revision of manuscript. TMG: analysed and interpreted the data, critical revision of manuscript. CL: analysed and interpreted the data, critical revision of manuscript. NLZ: analysed and interpreted the data, critical revision of manuscript. SAM: analysed and interpreted the data, critical revision of manuscript EPF: study concept and design, analysis and interpretation of data, critical revision of manuscript and study supervision.

  • Funding This study was made possible using funding from the NIH (R01NS113828).

  • 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.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the institutional review board of Mayo Clinic, Rochester, Minnesota, USA.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. Anonymised data used for this study are available from the corresponding authors on reasonable request.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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