Evidence map›Paper›PMID 39730779›Full record

ArticleScientific reports2024

Diagnostic abnormalities, disease severity and immunotherapy responsiveness in individuals with Down syndrome regression disorder.

Jonathan D Santoro, Saba Jafarpour, Laura Keehan, Mellad M Khoshnood, Lilia Kazerooni, Natalie K Boyd, Benjamin N Vogel, Lina Nguyen, Melanie Manning, Deepti Nagesh and 4 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Journal of child and adolescent psychopharmacology · 2026
    Article
  7. Precision medicine for Alzheimer's disease in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  8. Observational
  9. Article
  10. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Jonathan D SantoroDivision of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mailstop 82, Los Angeles, CA, 90027, USA. santoroj@usc.edu.
Saba JafarpourDivision of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mailstop 82, Los Angeles, CA, 90027, USA.
Laura KeehanDepartment of Pediatrics, Division of Medical Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Mellad M KhoshnoodDivision of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mailstop 82, Los Angeles, CA, 90027, USA.
Lilia KazerooniDivision of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mailstop 82, Los Angeles, CA, 90027, USA.
Natalie K BoydDivision of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mailstop 82, Los Angeles, CA, 90027, USA.
Benjamin N VogelDivision of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mailstop 82, Los Angeles, CA, 90027, USA.
Lina NguyenDivision of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mailstop 82, Los Angeles, CA, 90027, USA.
Melanie ManningDepartment of Pediatrics, Division of Medical Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Deepti NageshDivision of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mailstop 82, Los Angeles, CA, 90027, USA.
Noemi A SpinazziBenioff Children's Hospital, University of California San Francisco, Oakland, CA, USA.
Aaron D BestermanDepartment of Psychiatry, University of California San Diego, San Diego, CA, USA.
Eileen A QuinnDepartment of Pediatrics, University of Toledo, Toledo, OH, USA.
Michael S RafiiDepartment of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionDown Syndrome Regression Disorder (DSRD) is a neuropsychiatric condition causing insomnia, catatonia, encephalopathy, and obsessive-compulsive behavior in otherwise healthy individuals with Down syndrome (DS). Smaller cohorts have identified heterogenous diagnostic abnormalities which have predicted immunotherapy responsiveness although pattern analysis in a large cohort has never been performed.

methodsA multi-center, retrospective study of individuals with DSRD was performed. Individuals met international consensus criteria for DRSD and were aged 10-30 years. Clinical, demographic, and diagnostic data was extracted for all individuals. Serum studies were compared to a group of individuals with DS only.

resultsA total of 164 individuals with DSRD were identified. Individuals with DSRD were more likely to have a positive antinuclear antibody, low complement 3, abnormal cytokines, and elevated ferritin levels. In a minority of individuals, EEG (30%), MRI (33%) and cerebrospinal fluid (CSF) (21%) were abnormal. Individuals with CSF abnormalities demonstrated greater disease severity at diagnosis on the BFCRS and NPI-Q (p = 0.02 and p < 0.001). Abnormalities in cytokines (p = 0.03), neuroimaging (p < 0.001), and CSF (p = 0.02) were predictive of immunotherapy responsiveness. When MRI and LP were both abnormal or when EEG, MRI and LP were all abnormal, the odds of immunotherapy responsiveness approached 100% (p = 0.01, 95%CI: 1.75-105.1, OR: 13.56 and p = 0.02, 95%CI: 1.37-86.87, OR: 10.91, respectively).

conclusionsIn a population of individuals diagnosed with DSRD, abnormalities in serum cytokine levels, neuroimaging findings, and CSF analysis emerged as indicators of disease severity and responsiveness to immunotherapy.

Indexed as

Down SyndromeImmunotherapySeverity of Illness IndexAdolescentAdultChildCytokinesFemaleHumansMagnetic Resonance ImagingMaleRetrospective StudiesYoung AdultCytokinesCSFCytokineDiagnosticDown syndromeRegressionSerum

Identifiers

PMID39730779
PMCPMC11680819

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.