Sleep spindles as a predictor of cognitive motor dissociation and recovery of consciousness after acute brain injury | Nature Medicine

Nature Medicine volume 31, pages 1578–1585 (2025)Cite this article

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Cognitive motor dissociation (CMD) can improve the accuracy to predict recovery of behaviorally unresponsive patients with acute brain injury, but acquisition and analysis of task-based electroencephalography (EEG) are technically challenging. N2 sleep patterns, such as sleep spindles on EEG, have been associated with good outcomes, rely on similar thalamocortical networks as consciousness and could provide less technically challenging complementary outcome predictors. In this prospective observational cohort study of 226 acutely brain injured patients, well-formed sleep spindles (WFSS) were more likely present in those with CMD than in those without CMD, often preceding the detection of CMD. WFSS were associated with a shorter time to recovery of consciousness, and both CMD and WFSS independently predicted recovery of independence, controlling for age, admission neurological status and injury type. WFSS are seen in approximately every third behaviorally unresponsive patient after acute brain injury, frequently precede detection of CMD and are a promising complementary predictor for recovery of consciousness and functional independence.

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The primary patient-level data that support all the main analyses are available as part of Extended Data Figs. 4 and 5, including sleep data, CMD status, sedation data and outcomes data. Other individual patient data are not openly available due to reasons of sensitivity for patient privacy reasons.

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We thank the nurses, attending physicians, fellows and neurology residents of the neuroscience ICU for their overall support of this project. We are grateful to the National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NS106014; LM011826) and the Clinical and Translational Science Awards (UL1TR001873 from the National Center for Advancing Translational Sciences/NIH) for support of this study.

These authors contributed equally: Elizabeth E. Carroll, Qi Shen.

Department of Neurology, Columbia University Irving Medical Center, NewYork-Presbyterian Hospital, New York, NY, USA

Elizabeth E. Carroll, Qi Shen, Vedant Kansara, Nicole Casson, Andrew Michalak, Itamar Niesvizky-Kogan, Jaehyung Lim, Amy Postelnik, Matthew J. Viereck, Satoshi Egawa, Joshua Kahan, Jerina C. Carmona, Lucie Kruger, You Lim Song, Angela Velazquez, Catherine A. Schevon, Shivani Ghoshal, Sachin Agarwal, David Roh, Soojin Park, Paul Kent & Jan Claassen

NewYork-Presbyterian Hospital, New York, NY, USA

Elizabeth E. Carroll, Andrew Michalak, Itamar Niesvizky-Kogan, Jaehyung Lim, Amy Postelnik, Joshua Kahan, E. Sander Connolly, Shivani Ghoshal, Sachin Agarwal, David Roh, Soojin Park, Paul Kent & Jan Claassen

Department of Neurosurgery, Columbia University Irving Medical Center, NewYork-Presbyterian Hospital, New York, NY, USA

E. Sander Connolly

Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, USA

Soojin Park

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The study was conceived and designed by J. Claassen. Data were acquired and analyzed by E.E.C., Q.S., V.K., N.C., A.M., I.N.-K., J.L., A.P., M.V., S.E., J. Carmona, L.K., Y.L.S., A.V. and J. Claassen. The paper and figures were drafted by E.E.C., Q.S., V.K. and J. Claassen. Edits to the paper were provided by C.A.S., J.K., E.S.C., S.G., S.A., D.R., S.P. and P.K.

Correspondence to Jan Claassen.

The authors declare no competing interests. J. Claassen is a minority shareholder at iCE Neurosystems, but this amounts to less than $10,000 and less than 5% equity in the company. No technology from iCE Neurosystems was used for any of the study procedures, data acquisition or analysis presented here. None of the patients included in this study were managed using any technology from iCE Neurosystems.

Nature Medicine thanks Brian Edlow, Daniel Kondziella and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Jerome Staal, in collaboration with the Nature Medicine team.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

EEG, electroencephalography; WLST, withdrawal of list sustaining treatment.

The green box indicates K-complex followed by a well-formed sleep spindle (Extended Data Fig. 2A), the light blue box indicates well-formed sleep spindles (Extended Data Fig. 2B and 2C), and the purple box indicates rudimentary sleep spindles (Extended Data Fig. 2D and 2E).

Presence of K-complexes and vertex waves in the entire patient cohort (a), CMD positive patients (b), and CMD negative patients (c) was highly correlated with concomitant presence of sleep spindles.

Well-formed sleep spindles frequently preceded the detection of CMD.

Of those CMD negative patients with delayed sleep spindles, well-formed sleep spindles were still predictive of recovery of consciousness, and 12-month outcome. Similarly to CMD positive patients, when well-formed sleep spindles were present on EEG, they were likely to persist on subsequent EEG recordings.

Patients receiving “moderate” (p = 0.0002, OR = 0.4 [0.3, 0.7]) and “minimal” or “low” levels of sedation (p < 0.0001 OR = 0.5 [0.3, 0.7]) were less likely to have well-formed sleep spindles present when compared to those with no sedation.

Time to CRS-R ≥ 8 is significantly shorter than time to MCS + /EMCS (p = 0.04).

Time to detect WFSS is significantly shorter than time to detect CMD in the overall cohort (Panel a). Time to CRS-R ≥ 8 is shorter for those with CMD (Panel b) but not for those without CMD (Panel c) except for non-CMD patients with WFSS (Panel d). Amongst patients with WFSS, 35% (6 of 17) of patients with and 46% (25 of 54) of patients without CMD recovered consciousness (Panel e). Amongst patients without WFSS, 25% (4 of 16) of patients with and 21% (30 of 139) of patients without CMD recovered consciousness. Patients with CRS-R ≥ 8 are kept in orange and first detecting WFSS, CMD and CRS-R are indicated by a green diamond, blue triangle, and orange dot, respectively. CMD, cognitive motor dissociation; CRS-R, coma recovery scale-revised; well-formed sleep spindles, WFSS.

This schematic depicts the timeline of testing and results for an exemplary patient found to have well-formed sleep spindles, followed by positive CMD testing, and ultimately recovery of consciousness and long-term functional recovery.

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Carroll, E.E., Shen, Q., Kansara, V. et al. Sleep spindles as a predictor of cognitive motor dissociation and recovery of consciousness after acute brain injury. Nat Med 31, 1578–1585 (2025). https://doi.org/10.1038/s41591-025-03578-x

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Received: 04 October 2024

Accepted: 07 February 2025

Published: 03 March 2025

Issue Date: May 2025

DOI: https://doi.org/10.1038/s41591-025-03578-x

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Sleep spindles as a predictor of cognitive motor dissociation and recovery of consciousness after acute brain injury | Nature Medicine