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[Preprint]. 2023 Feb 13:rs.3.rs-2521595.
doi: 10.21203/rs.3.rs-2521595/v1.

Immunotherapy Responsiveness and Risk of Relapse in Down Syndrome Regression Disorder

Jonathan Santoro  1 , Noemi Spinazzi  2 , Robyn Filipink  2 , Panteha Hayati-Rezvan  2 , Ryan Kammeyer  2 , Lina Patel  2 , Elise Sannar  2 , Luke Dwyer  2 , Abhik Banerjee  2 , Mellad Khoshnood  2 , Sabaj Jafarpour  2 , Natalie Boyd  2 , Rebecca Partridge  2 , Grace Gombolay  2 , Alison Christy  2 , Diego Real de Asua  2 , Maria Del Carmen Ortega  2 , Melanie Manning  2 , Heather Van Mater  2 , Gordon Worley  2 , Cathy Franklin  2 , Maria Stanley  2 , Ruth Brown  2 , George Capone  2 , Elieen Quinn, Michael Rafii
Affiliations

Immunotherapy Responsiveness and Risk of Relapse in Down Syndrome Regression Disorder

Jonathan Santoro et al. Res Sq. .

Update in

  • Immunotherapy responsiveness and risk of relapse in Down syndrome regression disorder.
    Santoro JD, Spinazzi NA, Filipink RA, Hayati-Rezvan P, Kammeyer R, Patel L, Sannar EA, Dwyer L, Banerjee AK, Khoshnood M, Jafarpour S, Boyd NK, Partridge R, Gombolay GY, Christy AL, Real de Asua D, Del Carmen Ortega M, Manning MA, Van Mater H, Worley G, Franklin C, Stanley MA, Brown R, Capone GT, Quinn EA, Rafii MS. Santoro JD, et al. Transl Psychiatry. 2023 Aug 8;13(1):276. doi: 10.1038/s41398-023-02579-z. Transl Psychiatry. 2023. PMID: 37553347 Free PMC article.

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.

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Figures

Figure 1
Figure 1
Clinical features including behavioral and neuropsychiatric assessments over the study period.
Figure 2
Figure 2
Clinical features including behavioral and neuropsychiatric assessments over the study period for patients with and without neurologic relapse.
Figure 3
Figure 3
Neurodiagnostic abnormality presence in patients with (n = 44) and without (n = 38) neurologic relapse.
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