February 28, 2023; 100 (9) Research Article
Therapeutic Response in Pediatric Neuromyelitis Optica Spectrum Disorder
View ORCID ProfileRaffaella Pizzolato Umeton, Michael Waltz, Gregory S. Aaen, Leslie Benson, Mark Gorman, Manu Goyal, Jennifer S. Graves, Yolanda Harris, Lauren Krupp, Timothy E. Lotze, Nikita M. Shukla, Soe Mar, Jayne Ness, Mary Rensel, Teri Schreiner, Jan-Mendelt Tillema, Shelly Roalstad, Moses Rodriguez, John Rose, Emmanuelle Waubant, Bianca Weinstock-Guttman, Charles Casper, Tanuja Chitnis, on behalf of the US Network of Pediatric MS Centers
First published December 2, 2022, DOI: https://doi.org/10.1212/WNL.0000000000201625
Raffaella Pizzolato Umeton
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Michael Waltz
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Gregory S. Aaen
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Leslie Benson
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Mark Gorman
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Manu Goyal
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Jennifer S. Graves
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Yolanda Harris
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Lauren Krupp
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Timothy E. Lotze
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Nikita M. Shukla
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Soe Mar
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Jayne Ness
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Mary Rensel
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Teri Schreiner
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Jan-Mendelt Tillema
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Shelly Roalstad
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Moses Rodriguez
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
John Rose
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Emmanuelle Waubant
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Bianca Weinstock-Guttman
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Charles Casper
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Tanuja Chitnis
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Therapeutic Response in Pediatric Neuromyelitis Optica Spectrum Disorder
Raffaella Pizzolato Umeton, Michael Waltz, Gregory S. Aaen, Leslie Benson, Mark Gorman, Manu Goyal, Jennifer S. Graves, Yolanda Harris, Lauren Krupp, Timothy E. Lotze, Nikita M. Shukla, Soe Mar, Jayne Ness, Mary Rensel, Teri Schreiner, Jan-Mendelt Tillema, Shelly Roalstad, Moses Rodriguez, John Rose, Emmanuelle Waubant, Bianca Weinstock-Guttman, Charles Casper, Tanuja Chitnis, on behalf of the US Network of Pediatric MS Centers
Neurology Feb 2023, 100 (9) e985-e994; DOI: 10.1212/WNL.0000000000201625
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Abstract
Background and Objective Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune condition, which can lead to significant disability, and up to 3%–5% of the cases have a pediatric onset. There are limited studies to guide physicians in disease-modifying treatment (DMT) choices for children with NMOSD.
Methods This retrospective cohort study evaluated children with NMOSD cases followed at 12 clinics in the US Network of Pediatric MS Centers. Cases were classified as aquaporin-4 antibody positive (AQP4+) and double seronegative (DS) when negative for AQP4+ and for myelin oligodendrocyte glycoprotein (MOG) antibody. The effect of initial DMTs including rituximab, mycophenolate, azathioprine, and IV immunoglobulin (IVIg) on the annualized relapse rate (ARR) was assessed by negative binomial regression. Time to disability progression (EDSS score increase ≥1.0 point) was modeled with a Cox proportional-hazards model.
Results A total of 91 children with NMOSD were identified: 77 AQP4+ and 14 DS (85.7% females; 43.2% White and 46.6% African American). Eighty-one patients were started on a DMT, and 10 were treatment naive at the time of the analysis. The ARR calculated in all serogroups was 0.25 (95% CI 0.13–0.49) for rituximab, 0.33 (95% CI 0.19–0.58) for mycophenolate, 0.40 (95% CI 0.13–1.24) for azathioprine, and 0.54 (95% CI 0.28–1.04) for IVIg. The ARR in the AQP4+ subgroup was 0.28 (95% CI 0.14–0.55) for rituximab, 0.39 (95% CI 0.21–0.70) for mycophenolate, 0.41 (95% CI 0.13–1.29) for azathioprine, and 0.54 (95% CI 0.23–1.26) for IVIg. The ARR in the treatment-naive group was 0.97 (95% CI 0.58–1.60) in all serogroups and 0.91 (95% CI 0.53–1.56) in the AQP4+ subgroup. None of the initial DMT had a statistically significant effect on EDSS progression.
Discussion The use of DMTs, particularly rituximab, is associated with a lowered annualized relapse rate in children with NMOSD AQP4+.
Classification of Evidence This study provides Class IV evidence that use of disease-modifying treatments is associated with a lowered annualized relapse rate in children with NMOSD AQP4+.
Glossary
- ARR=
- annualized relapse rate;
- DCAC=
- Data Coordinating and Analysis Center;
- DMTs=
- disease-modifying treatments;
- EDSS=
- Expanded Disability Status Scale;
- LETM=
- longitudinally extensive transverse myelitis;
- MS=
- multiple sclerosis;
- NMOSD=
- neuromyelitis optica spectrum disorder
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editor was Associate Editor Renee Shellhaas, MD, MS.
Class of Evidence: NPub.org/coe
- Received January 7, 2022.
- Accepted in final form October 12, 2022.
- © 2022 American Academy of Neurology
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