Michael H Rivner1, Brandy M Quarles1, Jin-Xiu Pan2, Zheng Yu2, James F Howard3, Andrea Corse4, Mazen M Dimachkie5, Carlayne Jackson6, Tuan Vu7, George Small8, Robert P Lisak9, Jerry Belsh10, Ikjae Lee11, Richard J Nowak12, Vanessa Baute13, Stephen Scelsa14, J Americo Fernandes15, Zachary Simmons16, Andrea Swenson17, Richard Barohn5, R Bhavaraju Sanka6, Clifton Gooch7, Eroboghene Ubogu11, James Caress13, Mamatha Pasnoor5, Hongyan Xu18, Lin Mei2. 1. Department of Neurology, Augusta University, Augusta, Georgia. 2. Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio. 3. Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 4. Department of Neurology, The Johns Hopkins University, Baltimore, Maryland. 5. Department of Neurology, University of Kansas, Kansas City, Kansas. 6. Department of Neurology, University of Texas Health Science Center at San Antonio, San Antonio, Texas. 7. Department of Neurology, University of South Florida, Tampa, Florida. 8. Department of Neurology, Allegheny General Hospital, Pittsburgh, Pennsylvania. 9. Department of Neurology, Wayne State University, Detroit, Michigan. 10. Department of Neurology, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey. 11. Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama. 12. Department of Neurology, Yale University, New Haven, Connecticut. 13. Department of Neurology, Wake Forest University, Winston-Salem, North Carolina. 14. Department of Neurology, Mount Sinai-Beth Israel Hospital, New York, New York. 15. Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, Nebraska. 16. Department of Neurology, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania. 17. Department of Neurology, University of Iowa, Iowa City, Iowa. 18. Department of Population Health Sciences, Augusta University, Augusta, Georgia.
Abstract
INTRODUCTION: Our aim in this study was to identify the prevalence and clinical characteristics of LRP4/agrin-antibody-positive double-seronegative myasthenia gravis (DNMG). METHODS: DNMG patients at 16 sites in the United States were tested for LRP4 and agrin antibodies, and the clinical data were collected. RESULTS: Of 181 DNMG patients, 27 (14.9%) were positive for either low-density lipoprotein receptor-related protein 4 (LRP4) or agrin antibodies. Twenty-three DNMG patients (12.7%) were positive for both antibodies. More antibody-positive patients presented with generalized symptoms (69%) compared with antibody-negative patients (43%) (P ≤ .02). Antibody-positive patients' maximum classification on the Myasthenia Gravis Foundation of America (MGFA) scale was significantly higher than that for antibody-negative patients (P ≤ .005). Seventy percent of antibody-positive patients were classified as MGFA class III, IV, or V compared with 39% of antibody-negative patients. Most LRP4- and agrin-antibody-positive patients (24 of 27, 89%) developed generalized myathenia gravis (MG), but with standard MG treatment 81.5% (22 of 27) improved to MGFA class I or II during a mean follow-up of 11 years. DISCUSSION: Antibody-positive patients had more severe clinical disease than antibody-negative patients. Most DNMG patients responded to standard therapy regardless of antibody status.
INTRODUCTION: Our aim in this study was to identify the prevalence and clinical characteristics of LRP4/agrin-antibody-positive double-seronegative myasthenia gravis (DNMG). METHODS:DNMGpatients at 16 sites in the United States were tested for LRP4 and agrin antibodies, and the clinical data were collected. RESULTS: Of 181 DNMGpatients, 27 (14.9%) were positive for either low-density lipoprotein receptor-related protein 4 (LRP4) or agrin antibodies. Twenty-three DNMGpatients (12.7%) were positive for both antibodies. More antibody-positive patients presented with generalized symptoms (69%) compared with antibody-negative patients (43%) (P ≤ .02). Antibody-positive patients' maximum classification on the Myasthenia Gravis Foundation of America (MGFA) scale was significantly higher than that for antibody-negative patients (P ≤ .005). Seventy percent of antibody-positive patients were classified as MGFA class III, IV, or V compared with 39% of antibody-negative patients. Most LRP4- and agrin-antibody-positive patients (24 of 27, 89%) developed generalized myathenia gravis (MG), but with standard MG treatment 81.5% (22 of 27) improved to MGFA class I or II during a mean follow-up of 11 years. DISCUSSION: Antibody-positive patients had more severe clinical disease than antibody-negative patients. Most DNMGpatients responded to standard therapy regardless of antibody status.