Immunotherapy Responsiveness and Risk of Relapse in Down Syndrome Regression Disorder
Jonathan Santoro1, Noemi Spinazzi2, Robyn Filipink3, Penteha Rezvan4, Ryan Kammeyer5, Lina Patel6, Elise Sannar5, Luke Dwyer7, Abhik Banerjee8, Mellad Khoshnood9, Saba Jafarpour10, Natalie Boyd4, Rebecca Partidge11, Grace Gombolay12, Alison Christy13, Maria del Carmen Ortega14, Melanie Manning15, Heather Van Mater16, Gordon Worley16, Cathy Franklin17, Maria Stanley18, Ruth Brown19, George Capone20, Eileen Quinn21, Michael Rafii22
1Department of Neurology, Children's Hospital Los Angeles, 2Benioff Children's Hospital, 3Children'S Hospital of Pittsburgh of UPMC, 4Childrens Hospital Los Angeles, 5Childrens Hospital Colorado, 6Children's Hospital Colorado, 7Psychiatry, University of Utah, 8University of Southern California, 9Children's Hospital Los Angeles, 10Children’s Hospital of Los Angeles, 11Virginia Mason Health System, 12Emory University/Children'S Healthcare of Atlanta, 13Providence Health & Services, Pediatric Specialty Clinic, 14Clinica Universidad de Navarra, 15Stanford School of Medicine, 16Duke University, 17University of Queensland, 18University of Wisconsin, 19Virginia Commonwealth University, 20Kennedy Krieger Institute, 21University of Toledo, 22USC Alzheimer'S Therapeutic Research Institute
Objective:
This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation in persons with Down Syndrome Regression Disorder (DSRD).
Background:
Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. Although presumably polyfactorial, a minority of individuals with this condition have been found to have inflammatory biomarkers and are immunotherapy responsive. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation.
Design/Methods:
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.
Results:
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.
Conclusions:
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.