Detection of Brain Activation in Unresponsive Patients with Acute Brain Injury

Jan Claassen. M.D. et al.

2019년 6월 26일

N Engl J Med 2019;380:2497-2505.

DOI: 10.1056/NEJMoa1812757

Background

Brain activation in response to spoken motor commands can be detected by electroencephalography (EEG) in clinically unresponsive patients. The prevalence and prognostic importance of a dissociation between commanded motor behavior and brain activation in the first few days after brain injury are not well understood

Methods

We studied a prospective, consecutive series of patients in a single intensive care unit who had acute brain injury from a variety of causes and who were unresponsive to spoken commands, including some patients with the ability to localize painful stimuli or to fixate on or track visual stimuli. Machine learning was applied to EEG recordings to detect brain activation in response to commands that patients move their hands. The functional outcome at 12 months was determined with the Glasgow Outcome Scale–Extended (GOS-E; levels range from 1 to 8, with higher levels indicating better outcomes).

Results

A total of 16 of 104 unresponsive patients (15%) had brain activation detected by EEG at a median of 4 days after injury. The condition in 8 of these 16 patients (50%) and in 23 of 88 patients (26%) without brain activation improved such that they were able to follow commands before discharge. At 12 months, 7 of 16 patients (44%) with brain activation and 12 of 84 patients (14%) without brain activation had a GOS-E level of 4 or higher, denoting the ability to function independently for 8 hours (odds ratio, 4.6; 95% confidence interval, 1.2 to 17.1).

Conclusions

A dissociation between the absence of behavioral responses to motor commands and the evidence of brain activation in response to these commands in EEG recordings was found in 15% of patients in a consecutive series of patients with acute brain injury. (Supported by the Dana Foundation and the James S. McDonnell Foundation.)

Motor Command Protocol and Data Processing.

Each block in the motor command protocol consisted of eight trials alternating between the instructions “keep opening and closing your right (left) hand” and “stop opening and closing your right (left) hand” (Panel A). The 10 seconds of electroencephalographic (EEG) recording after the instructions were given were extracted and segmented in five epochs, each 2 seconds long, for further analysis (Panel B). This procedure resulted in 480 epochs in patients (5 epochs×2 instructions×8 trials×6 blocks) and 240 epochs in controls (5 epochs×2 instructions×8 trials×3 blocks). Power spectral density (PSD) analysis was applied to the obtained EEG matrix in four frequency bands (δ [1 to 3 Hz], θ [4 to 7 Hz], α [8 to 13 Hz], and β [14 to 30 Hz]) (Panel C). The resulting features were used to train and test a support vector machine (SVM). The classification performance of the SVM for a given recording was assessed as the area under the receiver-operating-characteristic curve (AUC).

요약

·         소개 : 급성 뇌 손상을 입은 무반응 환자에서 EEG(뇌파검사)를 이용해 음성 운동명령에 대한 뇌 활성화 감지빈도를 측정하고, 예후적인 중요성을 평가하는 전향적 코호트 연구이다.  

·         방법 : 2014년 7월부터 2017년 9월까지 단일기관 중환자실에 급성 뇌 손상으로 입원하여 음성 운동명령에 무반응을 보이는 401명의 환자 중 최종 104명을 대상으로 하였다. 손 움직임에 대한 언어적 명령을 제시하고, 침상에서 EEG를 기록한 후 머신 러닝 기법을 적용하여 뇌 활성화를 감지하였다. 주요 결과 변수는 12개월 후의 기능적 회복 상태로, Glasgow Outcome Scale-Extended(GOS-E)를 사용하여 평가하였다. 

·         결과 : 총 104명의 무반응 환자 중 16명(15%)에서 EEG를 통해 뇌 활성화가 감지되었고, 이중 8명(50%)은 퇴원 전까지 명령을 따를 수 있을 정도로 상태가 호전되었다. 뇌 활성화가 감지되지 않은 88명의 환자 중 23명(26%)에서도 유사한 회복이 나타났다. 12개월 후 기능적 예후를 평가한 결과, 뇌 활성화가 감지된 환자 16명 중 7명(44%)이, 뇌 활성화가 감지되지 않은 환자 84명중 12명(14%)이 GOS-E 4점 이상(8시간 이상 독립적인 생활 가능)으로 평가되었다.

·         결론 : 급성 뇌손상을 입은 연속환자군에서 운동 명령에 대한 행동적 반응이 없음에도 EEG를 통해 뇌 활성화가 감지되는 인지-운동 분리현상이 15%에서 관찰되었다.

·          의의 : 급성 뇌손상 환자의 초기 평가와 치료 결정 과정에서 EEG 기반의 뇌 활성화 탐지가 중요한 역할을 할 수 있음을 제시한다.