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Observational Study
. 2025 Oct:171:34-40.
doi: 10.1016/j.pediatrneurol.2025.07.007. Epub 2025 Jul 18.

Cerebral Blood Flow Abnormalities in Down Syndrome Regression Disorder

Mackenzie Silverman  1 , Panteha Hayati Rezvan  2 , Benjamin N Vogel  1 , Mariam M Yousuf  1 , Maeve C Lucas  1 , Lilia Kazerooni  1 , Saba Jafarpour  3 , Jonathan D Santoro  4
Affiliations
Observational Study

Cerebral Blood Flow Abnormalities in Down Syndrome Regression Disorder

Mackenzie Silverman et al. Pediatr Neurol. 2025 Oct.

Abstract

Background: This study aimed to examine cerebral blood flow velocity (CBFV) in the middle cerebral artery (MCA) and internal carotid artery (ICA) of individuals with Down syndrome (DS) and Down Syndrome Regression Disorder (DSRD).

Methods: A single-center, prospective observational study was performed to evaluate CBFV in individuals with DS and DSRD using transcranial Doppler (TCD) ultrasound. Individuals with DS without regression and DSRD were recruited in a 1:1 manner. TCD studies were performed using a standardized protocol for children.

Results: In total, 104 individuals were enrolled, with 60 (57.7%) having DSRD and 44 (42.3%) having DS only. Individuals with DSRD had lower average MCA values (mean difference: -6.89, 95% confidence interval [CI]: -12.88, -0.90; P = 0.024) and ICA values (-4.98, 95% CI: -9.58, -0.38; P = 0.034) when compared with individuals with DS only. These differences were more apparent in the left MCA (-8.97, 95% CI: -15.89, -2.06; P = 0.011) and left ICA (-5.65, 95% CI: -11.11, -0.19; P = 0.042). Age, hemodynamic measures, and neuropsychiatric disease severity did not modify the differences in MCA and ICA between patients with DSRD and DS. However, in patients with DSRD, MCA values decreased on average by -0.40 (95% CI: -0.78, -0.02; P = 0.038) for every unit increase in heart rate compared with patients with DS.

Conclusions: This study revealed CBFV alterations in individuals with DSRD when compared with DS alone, demonstrating reduced CBFV in both the MCA and ICA. These findings suggest disrupted cerebral autoregulation, potentially driven by the presence of catatonia in individuals with DSRD.

Keywords: Blood flow; Catatonia; Cerebrovascular; Down syndrome; Regression; Transcranial Doppler.

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Conflict of interest statement

Conflicts of interest The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: This study was supported by National Institute of Heart, Lung and Blood Institute (K23HL155898). Jonathan D. Santoro, MD, reports financial support was provided by National Institute of Child Health and Human Development. Dr. Santoro serves as a consultant for TG Therapeutics, UCB, and Cycle Pharmaceuticals on neuroimmunology topics unrelated to the data presented. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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