title: Cavum Septi Pellucidi in Symptomatic Former Professional Football Players.
abstract: Post-mortem studies reveal a high rate of cavum septi pellucidi (CSP) in chronic traumatic encephalopathy (CTE). It remains, however, to be determined whether or not the presence of CSP may be a potential in vivo imaging marker in populations at high risk to develop CTE. The aim of this study was to evaluate CSP in former professional American football players presenting with cognitive and behavioral symptoms compared with noncontact sports athletes. Seventy-two symptomatic former professional football players (mean age 54.53 years, standard deviation [SD] 7.97) as well as 14 former professional noncontact sports athletes (mean age 57.14 years, SD 7.35) underwent high-resolution structural 3T magnetic resonance imaging. Two raters independently evaluated the CSP, and interrater reliability was calculated. Within National Football League players, an association of CSP measures with cognitive and behavioral functioning was evaluated using a multivariate mixed effects model. The measurements of the two raters were highly correlated (CSP length: rho = 0.98; Intraclass Correlation Coefficient [ICC] 0.99; p < 0.0001; septum length: rho = 0.93; ICC 0.96; p < 0.0001). For presence versus absence of CSP, there was high agreement (Cohen kappa = 0.83, p < 0.0001). A higher rate of CSP, a greater length of CSP, as well as a greater ratio of CSP length to septum length was found in symptomatic former professional football players compared with athlete controls. In addition, a greater length of CSP was associated with decreased performance on a list learning task (Neuropsychological Assessment Battery List A Immediate Recall, p = 0.04) and decreased test scores on a measure of estimate verbal intelligence (Wide Range Achievement Test Fourth Edition Reading Test, p = 0.02). Given the high prevalence of CSP in neuropathologically confirmed CTE in addition to the results of this study, CSP may serve as a potential early in vivo imaging marker to identify those at high risk for CTE. Future research is needed to investigate the pathomechanism underlying the development of CSP after repetitive head impacts, and its potential association with neuropathologically confirmed CTE.
authors.affiliation: 1 Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.|2 Department of Child and Adolescent Psychiatry, Psychosomatic, and Psychotherapy, Ludwig-Maximilian-University , Munich, Germany .
authors.forename: Inga K
authors.initials: IK
authors.lastname: Koerte
authors.affiliation: 1 Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.|3 Department of Pediatric Neurology, Dr. von Hauner Children's Hospital, Ludwig-Maximilian-University , Munich, Germany .
authors.forename: Jakob
authors.initials: J
authors.lastname: Hufschmidt
authors.affiliation: 1 Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.|2 Department of Child and Adolescent Psychiatry, Psychosomatic, and Psychotherapy, Ludwig-Maximilian-University , Munich, Germany .
authors.forename: Marc
authors.initials: M
authors.lastname: Muehlmann
authors.affiliation: 4 Department of Biostatistics, Boston University School of Public Health , Boston, Massachusetts.|5 CTE Center, Boston University School of Medicine , Boston, Massachusetts.|6 Alzheimer's Disease Center, Boston University School of Medicine , Boston, Massachusetts.
authors.forename: Yorghos
authors.initials: Y
authors.lastname: Tripodis
authors.affiliation: 1 Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.|5 CTE Center, Boston University School of Medicine , Boston, Massachusetts.|7 Department of Anatomy and Neurobiology, Boston University School of Medicine , Boston, Massachusetts.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Stamm
authors.affiliation: 1 Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.
authors.forename: Ofer
authors.initials: O
authors.lastname: Pasternak
authors.affiliation: 1 Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.
authors.forename: Michelle Y
authors.initials: MY
authors.lastname: Giwerc
authors.affiliation: 1 Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Coleman
authors.affiliation: 5 CTE Center, Boston University School of Medicine , Boston, Massachusetts.|8 Interfaculty Initiative in Health Policy, Harvard University , Cambridge, Massachusetts.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Baugh
authors.affiliation: 5 CTE Center, Boston University School of Medicine , Boston, Massachusetts.
authors.forename: Nathan G
authors.initials: NG
authors.lastname: Fritts
authors.affiliation: 3 Department of Pediatric Neurology, Dr. von Hauner Children's Hospital, Ludwig-Maximilian-University , Munich, Germany .
authors.forename: Florian
authors.initials: F
authors.lastname: Heinen
authors.affiliation: 1 Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.|9 Department of Radiology, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.|10 Center for Clinical Spectroscopy, Department of Radiology, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.
authors.forename: Alexander
authors.initials: A
authors.lastname: Lin
authors.affiliation: 5 CTE Center, Boston University School of Medicine , Boston, Massachusetts.|6 Alzheimer's Disease Center, Boston University School of Medicine , Boston, Massachusetts.|7 Department of Anatomy and Neurobiology, Boston University School of Medicine , Boston, Massachusetts.|11 Departments of Neurology and Neurosurgery, Boston University School of Medicine , Boston, Massachusetts.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Stern
authors.affiliation: 1 Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.|9 Department of Radiology, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.|12 VA Boston Healthcare System , Brockton Division, Brockton, Massachusetts.
authors.forename: Martha E
authors.initials: ME
authors.lastname: Shenton
mesh_terms: D000328:Adult; D000368:Aged; D056352:Athletes; D001924:Brain Concussion / Q000175:diagnosis / Q000453:epidemiology; D000070627:Chronic Traumatic Encephalopathy / Q000175:diagnosis* / Q000453:epidemiology; D005538:Football / Q000293:injuries*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012688:Septum Pellucidum / Q000473:pathology*
keywords: MRI; biomarkers; head trauma; neurodegenerative disorders; traumatic brain injury