Augmentation du liquide cérébrospinal extra-axial chez les nourrissons à haut risque qui développent plus tard l'autisme

Aperçu: G.M.

Des études précédentes avaientsignalé que les nourrissons qui ont développé un trouble du spectre de l'autisme (TSA) ont eu une augmentation du liquide céphalo-rachidien (CSF) dans l'espace sous-arachnoïdien (c.-à-d. CSF extra-axial) de 6 à 24 mois. La présente étude a tenté de confirmer et d'étendre cette constatation dans un plus grand échantillon indépendant.

Les nourrissons qui ont développé un TSA ont eu un volume de CSF extra-axial significativement plus important à 6 mois comparativement aux deux groupes de comparaison sans TSA (18% de plus que les nourrissons à risque élevé sans TSA , Co = d = 0,54). Le volume de CSF extra-axial est resté élevé pendant 24 mois (d = 0,46). Les nourrissons qui avaient des symptômes d'autisme plus sévères ont un volume encore plus important de CSF extra-axial de 6 à 24 mois (24% plus élevé à 6 mois, d = 0,70; 15% plus élevé à 24 mois, d = 0,70). Le volume de CSF extra-axial à 6 mois prévoyait que les nourrissons à risque élevé seraient diagnostiqués avec TSA à 24 mois avec une précision globale de 69% et une sensibilité correspondante de 66% et une spécificité de 68%, validée en totalité dans un échantillon séparé. 

Biol Psychiatry. 2017 Mar 6. pii: S0006-3223(17)31217-9. doi: 10.1016/j.biopsych.2017.02.1095.

Increased Extra-axial Cerebrospinal Fluid in High-Risk Infants Who Later Develop Autism

Shen MD¹, Kim SH², McKinstry RC³, Gu H⁴, Hazlett HC², Nordahl CW⁵, Emerson RW², Shaw D⁶, Elison JT⁷, Swanson MR², Fonov VS⁸, Gerig G⁹, Dager SR⁶, Botteron KN³, Paterson S¹⁰, Schultz RT¹¹, Evans AC⁸, Estes AM¹², Zwaigenbaum L¹³, Styner MA², Amaral DG⁵, Piven J²; Infant Brain Imaging Study Network; Infant Brain Imaging Study Network, The Infant Brain Imaging Study (IBIS) Network is a National Institutes of Health–funded Autism Center of Excellence project and consists of a consortium of eight universities in the United States and Canada, Piven J¹⁴, Hazlett HC¹⁴, Chappell C¹⁴, Dager S¹⁵, Estes A¹⁵, Shaw D¹⁵, Botteron K¹⁶, McKinstry R¹⁶, Constantino J¹⁶, Pruett J¹⁶, Schultz R¹⁷, Zwaigenbaum L¹⁸, Elison J¹⁹, Evans AC²⁰, Collins DL²⁰, Pike GB²⁰, Fonov V²⁰, Kostopoulos P²⁰, Das S²⁰, Gerig G²¹, Styner M²², Gu H²³.

Author information

1

Carolina Institute for Developmental Disabilities and Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina; MIND Institute and Department of Psychiatry and Behavioral Sciences, University of California, Davis, School of Medicine, Sacramento, California. Electronic address: mark_shen@med.unc.edu

2

Carolina Institute for Developmental Disabilities and Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina.

3

Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missourt.

4

Carolina Institute for Developmental Disabilities and Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina; Department of Biostatistics, School of Global Public Health, University of North Carolina at Chapel Hill School of Global Public Health, Chapel Hill, North Carolina.

5

MIND Institute and Department of Psychiatry and Behavioral Sciences, University of California, Davis, School of Medicine, Sacramento, California.

6

Department of Radiology, University of Washington Medical Center, Seattle, Washington.

7

Institute of Child Development, University of Minnesota, Minneapolis, Minnesota.

8

Montreal Neurological Institute, McGill University, Montreal, Quebec.

9

Computer Science & Engineering, New York University Tandon School of Engineering, New York, New York.

10

Department of Psychology, Temple University, Philadelphia, Pennsylvania.

11

Center for Autism Research, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.

12

Department of Speech and Hearing Science, University of Washington, Seattle, Washington.

13

Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.

14

Clinical sites-University of North Carolina.

15

University of Washington.

16

Washington University.

17

Children's Hospital of Philadelphia.

18

University of Alberta.

19

University of Minnesota.

20

Data Coordinating Center-Montreal Neurological Institute.

21

Image Processing Core-New York University.

22

University of North Carolina.

23

Statistical Analysis Core-University of North Carolina.

Abstract

BACKGROUND:

We previously reported that infants who developed autism spectrum disorder (ASD) had increased cerebrospinal fluid (CSF) in the subarachnoid space (i.e., extra-axial CSF) from 6 to 24 months of age. We attempted to confirm and extend this finding in a larger independent sample.

METHODS:

A longitudinal magnetic resonance imaging study of infants at risk for ASD was carried out on 343 infants, who underwent neuroimaging at 6, 12, and 24 months. Of these infants, 221 were at high risk for ASD because of an older sibling with ASD, and 122 were at low risk with no family history of ASD. A total of 47 infants were diagnosed with ASD at 24 months and were compared with 174 high-risk and 122 low-risk infants without ASD.

RESULTS:

Infants who developed ASD had significantly greater extra-axial CSF volume at 6 months compared with both comparison groups without ASD (18% greater than high-risk infants without ASD; Cohen's d = 0.54). Extra-axial CSF volume remained elevated through 24 months (d = 0.46). Infants with more severe autism symptoms had an even greater volume of extra-axial CSF from 6 to 24 months (24% greater at 6 months, d = 0.70; 15% greater at 24 months, d = 0.70). Extra-axial CSF volume at 6 months predicted which high-risk infants would be diagnosed with ASD at 24 months with an overall accuracy of 69% and corresponding 66% sensitivity and 68% specificity, which was fully cross-validated in a separate sample.

CONCLUSIONS:

This study confirms and extends previous findings that increased extra-axial CSF is detectable at 6 months in high-risk infants who develop ASD. Future studies will address whether this anomaly is a contributing factor to the etiology of ASD or an early risk marker for ASD.

Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

PMID: 28392081

DOI: 10.1016/j.biopsych.2017.02.1095