Cerebrospinal fluid levels of amyloid precursor protein are associated with ventricular size in post-hemorrhagic hydrocephalus of prematurity.
BACKGROUND
Neurological outcomes of preterm infants with post-hemorrhagic hydrocephalus (PHH) remain among the worst in infancy, yet there remain few instruments to inform the treatment of PHH. We previously observed PHH-associated elevations in cerebrospinal fluid (CSF) amyloid precursor protein (APP), neural cell adhesion molecule-L1 (L1CAM), neural cell adhesion molecule-1 (NCAM-1), and other protein mediators of neurodevelopment.


OBJECTIVE
The objective of this study was to examine the association of CSF APP, L1CAM, and NCAM-1 with ventricular size as an early step toward developing CSF markers of PHH.


METHODS
CSF levels of APP, L1CAM, NCAM-1, and total protein (TP) were measured in 12 preterm infants undergoing PHH treatment. Ventricular size was determined using cranial ultrasounds. The relationships between CSF APP, L1CAM, and NCAM-1, occipitofrontal circumference (OFC), volume of CSF removed, and ventricular size were examined using correlation and regression analyses.


RESULTS
CSF levels of APP, L1CAM, and NCAM-1 but not TP paralleled treatment-related changes in ventricular size. CSF APP demonstrated the strongest association with ventricular size, estimated by frontal-occipital horn ratio (FOR) (Pearson R = 0.76, p = 0.004), followed by NCAM-1 (R = 0.66, p = 0.02) and L1CAM (R = 0.57,p = 0.055). TP was not correlated with FOR (R = 0.02, p = 0.95).


CONCLUSIONS
Herein, we report the novel observation that CSF APP shows a robust association with ventricular size in preterm infants treated for PHH. The results from this study suggest that CSF APP and related proteins at once hold promise as biomarkers of PHH and provide insight into the neurological consequences of PHH in the preterm infant.
Department of Neurological Surgery, Washington University in St. Louis, School of Medicine, Saint Louis, Missouri, United States of America.
Diego M
DM
Morales
Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
Richard
R
Holubkov
Department of Pediatrics, Washington University in St. Louis, School of Medicine, Saint Louis, Missouri, United States of America.
Terri E
TE
Inder
Department of Neurological Surgery, Washington University in St. Louis, School of Medicine, Saint Louis, Missouri, United States of America.
Haejun C
HC
Ahn
Department of Neurological Surgery, Washington University in St. Louis, School of Medicine, Saint Louis, Missouri, United States of America.
Deanna
D
Mercer
Department of Newborn Medicine, Washington University in St. Louis, School of Medicine, Saint Louis, Missouri, United States of America.
Rakesh
R
Rao
Department of Neurological Surgery, Washington University in St. Louis, School of Medicine, Saint Louis, Missouri, United States of America.
James P
JP
McAllister
Department of Neurology, Washington University in St. Louis, School of Medicine, Saint Louis, Missouri, United States of America; The Hope Center for Neurological Disorders, Washington University in St. Louis, School of Medicine, Saint Louis, Missouri, United States of America.
David M
DM
Holtzman
Department of Neurological Surgery, Washington University in St. Louis, School of Medicine, Saint Louis, Missouri, United States of America; Department of Pediatrics, Washington University in St. Louis, School of Medicine, Saint Louis, Missouri, United States of America; The Hope Center for Neurological Disorders, Washington University in St. Louis, School of Medicine, Saint Louis, Missouri, United States of America.
David D
DD
Limbrick
D016564:Amyloid beta-Protein Precursor / Q000097:blood / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D019002:CD56 Antigen / Q000097:blood / Q000134:cerebrospinal fluid; D002552:Cerebral Ventricles / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D006801:Humans; D006849:Hydrocephalus / Q000097:blood / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging; D007231:Infant, Newborn; D008297:Male; D039842:Neural Cell Adhesion Molecule L1 / Q000097:blood / Q000134:cerebrospinal fluid; D009929:Organ Size; D047928:Premature Birth; D014463:Ultrasonography
D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D019002:CD56 Antigen; C522918:NCAM1 protein, human; D039842:Neural Cell Adhesion Molecule L1