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Disorder of consciousness (DOC) is common in patients with acute brain injury (ABI) and it weighs heavily in goals of care discussion.1 Dopaminergic agents to support recovery have shown encouraging results in chronic DOC following traumatic brain injury (TBI) and are currently the most promising candidates to also support recovery during the acute post injury phase.2 Amantadine is a neurohormonal modulator that increases the concentration of dopamine at the synaptic cleft. Behavioural assessments of consciousness alone are often operator dependent, time consuming to obtain and may miss patients with covert consciousness.3 Our hypothesis is that resting Electroencephalogram (EEG) features follow a predictable course preceding behavioural recovery in patients with acute non-hypoxic-ischaemic brain injury receiving amantadine and may serve as biomarkers for recovery of consciousness.
We studied 44 patients with ABI that were not following commands and were on EEG monitoring before and after the start of amantadine. A full description of the methods is available in the online supplementary file.
From a cohort of 44 patients, 30 (68%) recovered consciousness prior to hospital discharge (online supplementary tables S1, S2).
Baseline predictors of recovery
Age, focal versus diffuse brain injury and admission Glasgow Coma Score were not associated with recovery of command following. Presence of sleep structures in the EEG (spindles and K-complexes) prior to starting amantadine was independently associated with recovery of command following (online supplementary table S3). Average spectrogram plots for each EEG recording classified according to the ‘ABCD’ model representing thalamocortical integrity were generated (figure 1A, online supplementary figure).4 The percent of patients that recovered command following did not increase hierarchically with higher ‘ABCD’ levels (figure 1B). Power spectral density analysis …
Contributors Study concept and design: AA and JC. Acquisition of Data: AA, CR, JAK, EM and KD. Analysis and interpretation of data: AA and JC. Drafting the manuscript: AA. Critical revision of the manuscript for important intellectual content: CR, JAK, CAD-N, KD, JAE, ARC, AB, DR, SP, SA, ESC and JC. Statistical analysis: AA, AE, KD and JC. Study supervision: JC.
Funding JC is supported by grant funding from the NIH R01 NS106014 and R03 NS112760, and the DANA Foundation. AA is supported by grant funding from the Miami Clinical and Translation Science Institute (CTSI), KL2 Career Development Award UL1TR002736. JC is a minority shareholder at iCE Neurosystems.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.