Immunotherapy responsiveness and risk of relapse in Down syndrome regression disorder

Jonathan D Santoro; Noemi A Spinazzi; Robyn A Filipink; Panteha Hayati-Rezvan; Ryan Kammeyer; Lina Patel; Elise A Sannar; Luke Dwyer; Abhik K Banerjee; Mellad Khoshnood; Saba Jafarpour; Natalie K Boyd; Rebecca Partridge; Grace Y Gombolay; Alison L Christy; Diego Real de Asua; Maria Del Carmen Ortega; Melanie A Manning; Heather Van Mater; Gordan Worley; Cathy Franklin; Maria A Stanley; Ruth Brown; George T Capone; Eileen A Quinn; Michael S Rafii

doi:10.1038/s41398-023-02579-z

Immunotherapy responsiveness and risk of relapse in Down syndrome regression disorder

Transl Psychiatry. 2023 Aug 8;13(1):276. doi: 10.1038/s41398-023-02579-z.

Authors

Jonathan D Santoro^{1

2}, Noemi A Spinazzi³, Robyn A Filipink⁴, Panteha Hayati-Rezvan⁵, Ryan Kammeyer⁶, Lina Patel⁷, Elise A Sannar⁷, Luke Dwyer⁸, Abhik K Banerjee⁹, Mellad Khoshnood⁹, Saba Jafarpour⁹, Natalie K Boyd⁹, Rebecca Partridge¹⁰, Grace Y Gombolay¹¹, Alison L Christy¹², Diego Real de Asua¹³, Maria Del Carmen Ortega¹⁴, Melanie A Manning¹⁵, Heather Van Mater¹⁶, Gordan Worley¹⁷, Cathy Franklin¹⁸, Maria A Stanley¹⁹, Ruth Brown²⁰, George T Capone²¹, Eileen A Quinn²², Michael S Rafii^{23

24}

Affiliations

¹ Division of Neurology, Children's Hospital Los Angeles, Los Angeles, CA, USA. santoroj@usc.edu.
² Department of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA. santoroj@usc.edu.
³ Department of Pediatrics, Benioff Children's Hospital, University of California San Francisco, San Francisco, CA, USA.
⁴ Division of Child Neurology, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
⁵ Division of Research on Children, Youth and Families, Keck School of Medicine of USC, Los Angeles, CA, USA.
⁶ Department of Neurology, Children's Hospital of Colorado, Aurora, CO, USA.
⁷ Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO, USA.
⁸ Department of Psychiatry, University of Utah, Salt Lake City, UT, USA.
⁹ Division of Neurology, Children's Hospital Los Angeles, Los Angeles, CA, USA.
¹⁰ Virginia Mason Health System, Issaquah, WA, USA.
¹¹ Department of Pediatrics, Division of Neurology Emory University and Children's Healthcare of Atlanta, Atlanta, GA, USA.
¹² Providence Health System, Portland, OR, USA.
¹³ Adult Down Syndrome Outpatient Clinic, Department of Internal Medicine, Fundación de Investigación Biomédica, Hospital Universitario de La Princesa, Madrid, Spain.
¹⁴ Department of Psychiatry, Clinica Universidad de Navarra, Madrid, Spain.
¹⁵ Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA.
¹⁶ Division of Rheumatology, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
¹⁷ Division of Pediatric Neurology and Developmental Medicine, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
¹⁸ Queensland Center for Intellectual and Developmental Disability, Mater Research Institute, The University of Queensland, South Brisbane, QLD, Australia.
¹⁹ Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
²⁰ Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA.
²¹ Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA.
²² Department of Pediatrics, University of Toledo College of Medicine and Life Science, Toledo, OH, USA.
²³ Department of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
²⁴ Alzheimer's Therapeutic Research Institute (ATRI), Keck School of Medicine at the University of Southern California, San Diego, CA, USA.

Abstract

Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation. A prospective, multi-center, non-randomized, observational study was performed. Patients met criteria for DSRD and were treated with IVIg. All patients underwent a standardized wean-off therapy after 9-12 months of treatment. Baseline, on-therapy, and relapse scores of the Neuropsychiatric Inventory Total Score (NPITS), Clinical Global Impression-Severity (CGI-S), and the Bush-Francis Catatonia Rating Scale (BFCRS) were used to track clinical symptoms. Eighty-two individuals were enrolled in this study. Patients had lower BFCRS (MD: -6.68; 95% CI: -8.23, -5.14), CGI-S (MD: -1.27; 95% CI: -1.73, -0.81), and NPITS scores (MD: -6.50; 95% CI: -7.53, -5.47) while they were on therapy compared to baseline. Approximately 46% of the patients (n = 38) experienced neurologic relapse with wean of IVIg. Patients with neurologic relapse were more likely to have any abnormal neurodiagnostic study (χ² = 11.82, P = 0.001), abnormal MRI (χ² = 7.78, P = 0.005), and abnormal LP (χ² = 5.45, P = 0.02), and a personal history of autoimmunity (OR: 6.11, P < 0.001) compared to patients without relapse. IVIg was highly effective in the treatment of DSRD. Individuals with a history of personal autoimmunity or neurodiagnostic abnormalities were more likely to relapse following weaning of immunotherapy, indicating the potential for, a chronic autoimmune etiology in some cases of DSRD.

Publication types

Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Down Syndrome* / therapy
Humans
Immunoglobulins, Intravenous
Immunotherapy
Prospective Studies
Recurrence

Substances

Immunoglobulins, Intravenous

Abstract

Publication types

MeSH terms

Substances

Grants and funding