Preliminary Study Of Brain Function And Prediction Of Conscious Awareness In Patients With Disorders Of Consciousness

Objective Stroke,craniocerebral trauma,hypoxic ischemic encephalopathy,encephalitis and other diseases can lead to disturbance of consciousness,which has high mortality and disability rate.Many of these patients would no longer regain consciousness and make families and society bear huge burden.Therefore,the evaluation of brain function in patients with disorders of consciousness and the accurate prediction of recovery of consciousness are the important direction of clinical study.For functional magnetic resonance imaging(fMRI)and positron emission tomography(PET)could not be completed by bedside,high cost of examination,and high risk for patients with conscious disorders,fMRI and PET were limited in clinical use.Because the clinical scale is highly subjective,therefore,we choose clinical combined with electrophysiological examination to establish an accurate and reliable assessment scale called ABMB for prediction of conscious awareness of patients with disorders of consciousness.We will carry out the event-related brain potentials(ERP)in patients with coma.We assumed if the cognitive component was detected in patients with disorders of consciousness,the consciousness of pathway was intact and had residual cortical functional recovery,the probability of consciousness recovery will greatly be increased.We also intended to compare the ERP before and after music stimulation in patients with disorder of consciousness,and find the brain mechanism of music on patients with disorder of consciousness.In addition,the changes in the circadian rhythm of melatonin in the coma patients were explored.Methods: Study 1.Between 2013 and 2017,all consecutive patients with consciousness disorders after acute ischemic stroke were recruited to the study.The demographic data,Full Outline of UnResponsiveness(FOUR)score,Glasgow Coma Scale(GCS)and Bispectral Index(BIS)were recorded at study entry and each day of Days 3-8 during the stroke period.We followed patients for 90 days to assess whether the subjects recovered conscious awareness.Logistic regression and receiver operating characteristic(ROC)curve analyses were used to evaluate the predictors’ abilities for outcome prognosis.Study 2.Between 2013 and 2018,all consecutive patients with consciousness disorders after acute cerebral infarction,cerebral hemorrhage,cerebral hypoxic encephalopathy were recruited to the study.The demographic data,Full Outline of UnResponsiveness(FOUR)score,Glasgow Coma Scale(GCS)and Bispectral Index(BIS)were recorded during the Days 3-7.We followed patients for 90 days to assess whether the subjects recovered conscious awareness and whether they survived or died.Receiver operating characteristic(ROC)curve analyses were used to evaluate the predictors’ abilities for outcome prognosis.Study 3.From 2015 to 2018,17 patients with brain injury were admitted to the department of neurology ICU of the First Affiliated Hospital of Anhui Medical University.The general data(age,sex,disease,onset time,CRS-R score and 6-month prognosis)of the patients were recorded.20 patients in the normal control group were matched by age and sex.Silence EEG recorded for 5 minutes,then acquired the first oddball paradigm ERP EEG,after reset for 5 minutes,listened to 5 minutes symphonic music " Spring Festival Overture"(a happy music,familiar with Chinese people),the second oddball paradigm ERP EEG recored.ERP results of the amplitudes of MMN and P300 were observed between groups(disorder of consciousness group and conscious awareness control group;before and after music).Study 4.From April 2016 to August 2016,6 patients with consciousness disorders after cerebral hemorrhage,cerebral trauma were included in the study.We recorded patients with general information(age,gender,disease),CT type,GCS score,APACHEII score,awareness recovery time,3 months GOS score.Venous blood was collected at 8 time points at Day3 and Day4(night with the eye mask),and melatonin levels were detected by ELASA.The periodic rhythm was observed,and the reproducibility was compared between Day3 and Day4.Results: Study 1.We assessed a total of 102 patients.23(23%)patients died without awareness recovery,whereas 61(60%)patients regained conscious awareness.The earliest time with the greatest ability to predict conscious awareness recovery occurred at Day 3 after stroke,and the area under the ROC curve(AUC)of the multivariate model was 0.948(95% confidence interval(CI)0.885 to 0.982).Age,BIS,motor response and brainstem responses were independent predictors for conscious awareness recovery.We subsequently created a 20-point score termed “ABMB” based on their coefficients in the Day 3 model.The AUC of ABMB at Day 3 was 0.931(95% CI 0.882 to 0.980).The ABMB also showed good predictive ability at Days 4 and 5.The ABMB score showed a higher AUC than BIS,GCS,FOUR score and admission NIHSS(p< 0.05).Study 2.A total of 140 patients were included in the Study.After 90 days of follow-up,82 cases(58.6%)recovered awareness and died in 36 cases(25.7%).The ABMB score of consciousness recovery group(16 ± 2)was significantly higher than that of consciousness non-recovery group(10±3),P < 0.001.The ABMB score in the 3 month survival group(15±3)was significantly higher than that in death group(9±3),P < 0.001.The prediction of awareness recovery with ROC analysis showed that the AUC of ABMB was 0.934(95%CI 0.879 to 0.969),higher than BIS,GCS score and FOUR scale(P <0.05).The prediction of death with ROC analysis showed that the AUC of ABMB was 0.904(95% CI 0.843 to 0.947),higher than the GCS score and the FOUR scale(p<0.05).For study of artificial airway of disorders of consciousness,we included 84 patients.After 90 days of follow-up,35 cases(41.7%)recovered consciousness and died in 33 cases(29.3%).The ABMB score of consciousness recovery group(15±2)was significantly higher than that of consciousness non-recovery group(10±3),P < 0.001.The ABMB score in the 3 month survival group(14±3)was significantly higher than that in death group(9±3),and P < 0.001.The prediction of awareness recovery with ROC analysis showed that the AUC of ABMB was 0.935(95%CI 0.885 to 0.985),higher than BIS,GCS score and FOUR scale(P < 0.05).The prediction of death with ROC analysis showed that the AUC of ABMB was 0.862(95% CI 0.770 to 0.928),higher than the BIS,GCS score and the FOUR scale(p<0.05).Study 3.89 % of the patients with recovery of consciousness detected MMN,and 50 % of the patients had MMN did not recover consciousness.A total of 6 patients(35 %)in the disorders of consciousness group detected significant P300.83% patients had P300 improved CRS-R in 6 months.The amplitude(2.4±2.6 uV)of MMN atCz in disorders of consciousness group was higher than that of control group(4.5±1.7 uV),p < 0.05.The amplitude of MMN was 0.8±2.5 uV at Fz before music was lowere than after music(3.3±3.0 uV)in patients with consciousness disorders(p < 0.05).Study 4.By Spearman correlation test,there are 3 cases(Patient1,Patient2,Patient3)with good repeatability inmelatonin levels,P < 0.05.Patient 2 and Patient 4 retained a certain high-night and low-day secretion,and both has good prognosis(GOS 5).The relationship between average melatonin level in patients and the GOS score was tested by Spearman correlation,which suggest no significant correlation(r =-0.12,P=0.822).The average level of melatonin in patients with the GCS score has no significant correlation by Spearman correlation test(r=0.465,P=0.15).Before the intervention at Day 3 night(494.8 ± 254.0ng/L)and Day 4 night(522 ± 252.0ng/L)at night,no significant difference was fountd(p>0.05).Conclusions: Study 1.The ABMB score accurately identified patients who will recover conscious awareness within 90 days after acute severe ischemic stroke and thus provides a useful outcome message for clinicians and relatives.Study 2.The ABMB score can accurately identified patients who will recover conscious awareness and who will survive within 90 days after acute severe ischemic stroke,cerebral hemorrhage and cerebral infarction,ischemic encephalopathy and cerebral trauma,and also in patients with artificial airway.The predictive value and ability of ABMB were better than those of GCS score,FOUR scale and bispectral index.Study 3.After listening to happy music,the patients could induce higher amplitude MMN and increase the detection rate of MMN and P300,suggesting that the patients increased attention and working memory after listening to music,increased mobilization of conscious resources,more brain contact,conducing to promote recovery.The auditory ERP study of patients with consciousness disorder can be carried out after music stimulation,fully stimulate the " potential" of patients,and test the real cognitive ability of patients.Study 4.Some patients with coma due to sever brain injury still had a certain characteristics of periodical of melatonin secretion.The prognosis may be better in patients with better reproducibility and retention of a certain circadian rhythm.The average level of melatonin has no significant correlation with the prognosis.The level of melatonin was not elevated in patients with coma by the intervention of eye mask and earplugs.