title: Structural brain anomalies in healthy adolescents in the NCANDA cohort: relation to neuropsychological test performance, sex, and ethnicity.
abstract: 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.
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA, 94305-5723, USA. edie@stanford.edu.
authors.forename: Edith V
authors.initials: EV
authors.lastname: Sullivan
authors.affiliation: Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Barton
authors.initials: B
authors.lastname: Lane
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA, 94305-5723, USA.|Center for Health Sciences, SRI International, Menlo Park, CA, USA.
authors.forename: Dongjin
authors.initials: D
authors.lastname: Kwon
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Meloy
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Susan F
authors.initials: SF
authors.lastname: Tapert
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Brown
authors.affiliation: Center for Health Sciences, SRI International, Menlo Park, CA, USA.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Colrain
authors.affiliation: Center for Health Sciences, SRI International, Menlo Park, CA, USA.
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Baker
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: De Bellis
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Duncan B
authors.initials: DB
authors.lastname: Clark
authors.affiliation: Departments of Psychiatry and Behavioral Neuroscience, Oregon Health & Sciences University, Portland, OR, USA.
authors.forename: Bonnie J
authors.initials: BJ
authors.lastname: Nagel
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA, 94305-5723, USA.|Center for Health Sciences, SRI International, Menlo Park, CA, USA.
authors.forename: Kilian M
authors.initials: KM
authors.lastname: Pohl
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA, 94305-5723, USA.|Center for Health Sciences, SRI International, Menlo Park, CA, USA.
authors.forename: Adolf
authors.initials: A
authors.lastname: Pfefferbaum
mesh_terms: D000293:Adolescent; D001921:Brain / Q000002:abnormalities* / Q000000981:diagnostic imaging* / Q000254:growth & development / Q000473:pathology; D002648:Child; D005006:Ethnicity; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D021621:Imaging, Three-Dimensional; D033162:Incidental Findings; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D009929:Organ Size; D010363:Pattern Recognition, Automated; D011446:Prospective Studies; D012017:Referral and Consultation; D012737:Sex Factors; D055815:Young Adult
keywords: Brain anomaly; Development, adolescence; Dysmorphology; Incidental findings