Structural brain anomalies in healthy adolescents in the NCANDA cohort: relation to neuropsychological test performance, sex, and ethnicity
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Structural MRI of volunteers deemed “normal” following clinical interview provides a window into normal brain developmental morphology but also reveals unexpected dysmorphology, commonly known as “incidental findings.” Although unanticipated, these anatomical findings raise questions regarding possible treatment that could even ultimately require neurosurgical intervention, which itself carries significant risk but may not be indicated if the anomaly is nonprogressive or of no functional consequence. Neuroradiological readings of 833 structural MRI from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) cohort found an 11.8 % incidence of brain structural anomalies, represented proportionately across the five collection sites and ethnic groups. Anomalies included 26 mega cisterna magna, 15 subarachnoid cysts, 12 pineal cysts, 12 white matter dysmorphologies, 5 tonsillar ectopias, 5 prominent perivascular spaces, 5 gray matter heterotopias, 4 pituitary masses, 4 excessively large or asymmetrical ventricles, 4 cavum septum pellucidum, 3 developmental venous anomalies, 1 exceptionally large midsagittal vein, and single cases requiring clinical followup: cranio-cervical junction stenosis, parietal cortical mass, and Chiari I malformation. A case of possible demyelinating disorder (e.g., neuromyelitis optica or multiple sclerosis) newly emerged at the 1-year NCANDA followup, requiring clinical referral. Comparing test performance of the 98 anomalous cases with 619 anomaly-free no-to-low alcohol consuming adolescents revealed significantly lower scores on speed measures of attention and motor functions; these differences were not attributed to any one anomaly subgroup. Further, we devised an automated approach for quantifying posterior fossa CSF volumes for detection of mega cisterna magna, which represented 26.5 % of clinically identified anomalies. Automated quantification fit a Gaussian distribution with a rightward skew. Using a 3SD cut-off, quantification identified 22 of the 26 clinically-identified cases, indicating that cases with percent of CSF in the posterior-inferior-middle aspect of the posterior fossa ≥3SD merit further review, and support complementing clinical readings with objective quantitative analysis. Discovery of asymptomatic brain structural anomalies, even when no clinical action is indicated, can be disconcerting to the individual and responsible family members, raising a disclosure dilemma: refrain from relating the incidental findings to avoid unnecessary alarm or anxiety; or alternatively, relate the neuroradiological findings as “normal variants” to the study volunteers and family, thereby equipping them with knowledge for the future should they have the occasion for a brain scan following an illness or accident that the incidental findings predated the later event.
KeywordsBrain anomaly Dysmorphology Development, adolescence Incidental findings
Compliance with ethical standard
This work was supported by the U.S. National Institute on Alcohol Abuse and Alcoholism with co-funding from the National Institute on Drug Abuse, the National Institute of Mental Health, and the National Institute of Child Health and Human Development [NCANDA grant numbers: AA021697 (A.P. + K.M.P.), AA021695 (S.A.B. + S.F.T.), AA021692 (S.A.B. + S.F.T.), AA021696 (I.M.C. + F.C.B.), AA021681 (M.D.D.B.), AA021690 (D.B.C.), AA021691 (B.N.)]. Additional funding supported E.V.S. (AA017168).
Conflict of interest
The authors declare that they have no conflict of interest with the work reported herein.
Informed consent was obtained from all individual participants, parents, or legal guardians who were majority, and assent from minors included in the study.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
- Barkovich, A. J., Kjos, B. O., Norman, D., & Edwards, M. S. (1989). Revised classification of posterior fossa cysts and cystlike malformations based on the results of multiplanar MR imaging. AJR. American Journal of Roentgenology, 153(6), 1289–1300. doi: 10.2214/ajr.153.6.1289.CrossRefPubMedGoogle Scholar
- Brown, S. A., Brumback, T., Tomlinson, K., Cummins, K., Thompson, W. K., Nagel, B. J., et al. (2015). The National Consortium on alcohol and NeuroDevelopment in adolescence (NCANDA): a multi-site study of adolescent development and substance use. Journal of Studies on Alcohol and Drugs, 76(6), 895–908.CrossRefPubMedPubMedCentralGoogle Scholar
- Giedd, J. N., Raznahan, A., Alexander-Bloch, A., Schmitt, E., Gogtay, N., & Rapoport, J. L. (2014). Child psychiatry branch of the National Institute of Mental Health longitudinal structural magnetic resonance imaging study of human brain development. Neuropsychopharmacology, 40(1), 43–49. doi: 10.1038/npp.2014.236.CrossRefPubMedPubMedCentralGoogle Scholar
- Gonsette, R., & Andre-Balisaux, G. (1968). A new technic of lumbosacral radiculography using a resorbable hydrosoluble medium without spinal anesthesia. Ann Radiol (Paris), 11(3), 141–145.Google Scholar
- Gur, R. C., Richard, J., Hughett, P., Calkins, M. E., Macy, L., Bilker, W. B., et al. (2010). A cognitive neuroscience-based computerized battery for efficient measurement of individual differences: standardization and initial construct validation. Journal of Neuroscience Methods, 187(2), 254–262. doi: 10.1016/j.jneumeth.2009.11.017.CrossRefPubMedGoogle Scholar
- Gur, R. C., Richard, J., Calkins, M. E., Chiavacci, R., Hansen, J. A., Bilker, W. B., et al. (2012). Age group and sex differences in performance on a computerized neurocognitive battery in children age 8-21. Neuropsychology, 26(2), 251–265. doi: 10.1037/a0026712.CrossRefPubMedPubMedCentralGoogle Scholar
- Hartwigsen, G., Siebner, H. R., Deuschl, G., Jansen, O., & Ulmer, S. (2010). Incidental findings are frequent in young healthy individuals undergoing magnetic resonance imaging in brain research imaging studies: a prospective single-center study. Journal of Computer Assisted Tomography, 34(4), 596–600. doi: 10.1097/RCT.0b013e3181d9c2bb.CrossRefPubMedGoogle Scholar
- Kaiser, D., Leach, J., Vannest, J., Schapiro, M., Holland, S., & Cincinnati, M. R. I. o. N. A. C (2015). Unanticipated findings in pediatric neuroimaging research: prevalence of abnormalities and process for reporting and clinical follow-up. Brain Imaging and Behavior, 9(1), 32–42. doi: 10.1007/s11682-014-9327-7.CrossRefPubMedGoogle Scholar
- Kumra, S., Ashtari, M., Anderson, B., Cervellione, K. L., & Kan, L. (2006). Ethical and practical considerations in the management of incidental findings in pediatric MRI studies. Journal of the American Academy of Child and Adolescent Psychiatry, 45(8), 1000–1006. doi: 10.1097/01.chi.0000222786.49477.a8.CrossRefPubMedGoogle Scholar
- Pfefferbaum, A., Rohlfing, T., Pohl, K. M., Lane, B., Chu, W., Kwon, D., et al. (2015). Adolescent development of cortical and white matter structure in the NCANDA Sample: Role of Sex, Ethnicity, Puberty, and Alcohol Drinking. Cereb Cortex, doi: 10.1093/cercor/bhv205.
- Raznahan, A., Lee, Y., Stidd, R., Long, R., Greenstein, D., Clasen, L., et al. (2010). Longitudinally mapping the influence of sex and androgen signaling on the dynamics of human cortical maturation in adolescence. Proceedings of the National Academy of Sciences of the United States of America, 107(39), 16988–16993. doi: 10.1073/pnas.1006025107.CrossRefPubMedPubMedCentralGoogle Scholar
- Raznahan, A., Lerch, J. P., Lee, N., Greenstein, D., Wallace, G. L., Stockman, M., et al. (2011). Patterns of coordinated anatomical change in human cortical development: a longitudinal neuroimaging study of maturational coupling. Neuron, 72(5), 873–884. doi: 10.1016/j.neuron.2011.09.028.CrossRefPubMedPubMedCentralGoogle Scholar
- Reneman, L., de Win, M. M., Booij, J., van den Brink, W., den Heeten, G. J., Freling, N., et al. (2012). Incidental head and neck findings on MRI in young healthy volunteers: prevalence and clinical implications. AJNR. American Journal of Neuroradiology, 33(10), 1971–1974. doi: 10.3174/ajnr.A3217.CrossRefPubMedGoogle Scholar
- Storsve, A. B., Fjell, A. M., Tamnes, C. K., Westlye, L. T., Overbye, K., Aasland, H. W., et al. (2014). Differential longitudinal changes in cortical thickness, surface area and volume across the adult life span: regions of accelerating and decelerating change. The Journal of Neuroscience, 34(25), 8488–8498. doi: 10.1523/JNEUROSCI.0391-14.2014.CrossRefPubMedGoogle Scholar
- Sullivan, E. V., Pfefferbaum, A., Rohlfing, T., Baker, F. C., Padilla, M. L., & Colrain, I. M. (2011). Developmental change in regional brain structure over 7 months in early adolescence: comparison of approaches for longitudinal atlas-based parcellation. NeuroImage, 57, 214–224. doi: 10.1016/j.neuroimage.2011.04.003.CrossRefPubMedPubMedCentralGoogle Scholar
- Sullivan, E. V., Brumback, T., Tapert, S. F., Fama, R., Prouty, D., Brown, S. A., et al. (2016). Cognitive, emotion control, and motor performance of adolescents in the NCANDA study: Contributions from alcohol consumption, age, sex, ethnicity, and family history of addiction. Neuropsychology, 30(4), 449–473. doi: 10.1037/neu0000259.
- Wolf, S. M., Lawrenz, F. P., Nelson, C. A., Kahn, J. P., Cho, M. K., Clayton, E. W., et al. (2008). Managing incidental findings in human subjects research: analysis and recommendations. The Journal of Law, Medicine & Ethics, 36(2), 219–248 211. doi: 10.1111/j.1748-720X.2008.00266.x.CrossRefGoogle Scholar
- Wood, S. N. (2011). Fast stable restricted maximum likelihood and marginal likelihood estimation of semiparametric generalized linear models. Fast stable restricted maximum likelihood and marginal likelihood estimation of semiparametric generalized linear models. Journal of the Royal Statistical Society (B), 73(1), 3–36.CrossRefGoogle Scholar