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. 2024 Oct;14(5):e200324.
doi: 10.1212/CPJ.0000000000200324. Epub 2024 Aug 15.

Cavum Septum Pellucidum in Former American Football Players: Findings From the DIAGNOSE CTE Research Project

Hector Arciniega  1 , Leonard B Jung  1 , Fatima Tuz-Zahra  1 , Yorghos Tripodis  1 , Omar John  1 , Nicholas Kim  1 , Holly W Carrington  1 , Evdokiya E Knyazhanskaya  1 , Arushi Chamaria  1 , Katherine Breedlove  1 , Tim L T Wiegand  1 , Daniel Daneshvar  1 , Tashrif Billah  1 , Ofer Pasternak  1 , Michael J Coleman  1 , Charles H Adler  1 , Charles Bernick  1 , Laura J Balcer  1 , Michael L Alosco  1 , Alexander P Lin  1 , Inga K Koerte  1 , Jeffrey L Cummings  1 , Eric M Reiman  1 , Robert A Stern  1 , Sylvain Bouix  1 , Martha E Shenton  1 ; DIAGNOSE CTE Research Project
Collaborators, Affiliations

Cavum Septum Pellucidum in Former American Football Players: Findings From the DIAGNOSE CTE Research Project

Hector Arciniega et al. Neurol Clin Pract. 2024 Oct.

Erratum in

Abstract

Background and objectives: Exposure to repetitive head impacts (RHI) is linked to the development of chronic traumatic encephalopathy (CTE), which can only be diagnosed at post-mortem. The presence of a cavum septum pellucidum (CSP) is a common finding in post-mortem studies of confirmed CTE and in neuroimaging studies of individuals exposed to RHI. This study examines CSP in living former American football players, investigating its association with RHI exposure, traumatic encephalopathy syndrome (TES) diagnosis, and provisional levels of certainty for CTE pathology.

Methods: Data from the DIAGNOSE CTE Research Project were used to compare the presence and ratio of CSP in former American football players (n = 175), consisting of former college (n = 58) and former professional players (n = 117), and asymptomatic unexposed controls without RHI exposure (n = 55). We further evaluated potential associations between CSP measures and cumulative head impact index (CHII) measures (frequency, linear acceleration, and rotational force), a TES diagnosis (yes/no), and a provisional level of certainty for CTE pathology (suggestive, possible, and probable).

Results: Former American football players exhibited a higher CSP presence and ratio than unexposed asymptomatic controls. Among player subgroups, professional players showed a greater CSP ratio than former college players and unexposed asymptomatic controls. Among all football players, CHII rotational forces correlated with an increased CSP ratio. No significant associations were found between CSP measures and diagnosis of TES or provisional levels of certainty for CTE pathology.

Discussion: This study confirms previous findings, highlighting a greater prevalence of CSP and a greater CSP ratio in former American football players compared with unexposed asymptomatic controls. In addition, former professional players showed a greater CSP ratio than college players. Moreover, the relationship between estimates of CHII rotational forces and CSP measures suggests that cumulative frequency and strength of rotational forces experienced in football are associated with CSP. However, CSP does not directly correlate with TES diagnosis or provisional levels of certainty for CTE, indicating that it may be a consequence of RHI associated with rotational forces. Further research, especially longitudinal studies, is needed for confirmation and to explore changes over time.

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Conflict of interest statement

C.H. Adler consulted for Avion, CND Life Sciences, Jazz, and PreCon Health; LJB is Editor-in-Chief of the Journal of Neuro-Ophthalmology and is a paid consultant to Biogen (Cambridge, MA, USA); C. Bernick receives research support from the Ultimate Fighting Championship, Top Rank promotions, Haymon Boxing, Las Vegas Raiders, and Professional Bull Riders. He is a paid consultant for Aurora Concussion Therapy Systems, Inc. (St. Paul, MN); A.P. Lin consulted for Agios, BioMarin, and Moncton MRI. He is a co-founder of BrainSpec, Inc; J.L. Cummings has provided consultation to Acadia, Alkahest, AlphaCognition, AriBio, Avanir, Axsome, Behren Therapeutics, Biogen, Biohaven, Cassava, Cortexyme, Diadem, EIP Pharma, Eisai, GemVax, Genentech, Green Valley, Grifols, Janssen, LSP, Merck, NervGen, Novo Nordisk, Oligomerix, Ono, Otsuka, PRODEO, Prothena, ReMYND, Renew, Resverlogix, Roche, Signant Health, Suven, United Neuroscience, and Unlearn AI pharmaceutical, assessment, and investment companies; E.M. Reiman is a compensated scientific advisor for Alkahest, Alzheon, Aural Analytics, Denali, Green Valley, Retromer Therapeutics, and Vaxxinity and is a cofounder of ALZPath; R.A. Stern is a paid consultant to Biogen (Cambridge, MA, USA) and Lundbeck (Copenhagen, Denmark). He is a member of the Board of Directors of King-Devick Technologies, Inc. (Chicago, IL, USA), and he receives royalties for published neuropsychological tests from Psychological Assessment Resources, Inc. (Lutz, FL, USA). He has been a member of the Medical Science Committee for the National Collegiate Athletic Association Student-Athlete Concussion Injury Litigation; I.K. Koerte receives funding for a collaborative project from Abbott Inc. She receives royalties for book chapters. Her spouse is an employee at Siemens AG and a stockholder of Siemens AG and Siemens Healthineers. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.

Figures

Figure 1
Figure 1. Variations in the Septum Pellucidum
(A) A visible septum pellucidum, which is the common observation. It is a thin triangular double membrane that separates the frontal horns of the right and left lateral ventricles of the brain. It extends between the anterior portion of the corpus callosum and the body of the fornix. (B) Visible (present) CSP is defined by cerebral spinal fluid being visible between 2 leaflets of the septum pellucidum as illustrated in a coronal slice. (C) The red double arrow line illustrates the widest area of the septum in the midsagittal plane. Measures were done from the genu to the splenium of the corpus callosum. (D) CSP et vergae where the 2 membranes are continuous. (E) CSP et cavum vergae detached at the splenium. For CSP et vergae and cavum vergae, we only report rate. CSP = cavum septum pellucidum.
Figure 2
Figure 2. Group-Level Differences in CSP Ratio
(A) Data from former American football players and unexposed asymptomatic controls indicate a greater CSP ratio in former American football players. (B) The dichotomized dataset illustrates a significantly greater CSP ratio in former professional players compared with unexposed asymptomatic controls and former college players. Note: n.s. indicates no significance, * indicates p < 0.05, ** indicates p < 0.01, and error bars represent 95% confidence intervals. CSP = cavum septum pellucidum.
Figure 3
Figure 3. Correlations With CHII Rotational Acceleration
Bivariate Pearson correlation between CSP ratio and CHII-R. Results indicate that CSP ratio is correlated with increased CHII-R. CHII-R = cumulative head impact index-rotational acceleration; CSP = cavum septum pellucidum.
See this image and copyright information in PMC

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