弥散张量成像对意识障碍患者诊断与预后评估的作用

目的探讨弥散张量成像（DTI）对意识障碍（DOC）患者的临床应用价值及其各指标变化规律。 方法选取自2014年1月至2015年12月陆军总医院附属八一脑科医院临床诊断为DOC的患者[植物状态（VS）患者56例,微意识状态（MCS）患者19例]进行弥散张量扫描,分别收集脑干、丘脑、皮层下三个相关的感兴趣区域评价FA、MD等指标数据。对不同意识状态的两组的参数值进行统计学分析,并将感兴趣区的各向异性（FA）、平均弥散率（MD）均值与临床昏迷恢复量表（CRS-R）评分进行相关性分析。 结果VS组FA值明显低于MCS组,差异具有统计学意义（P<0.05）;MD值则高于MCS组,差异具有统计学意义（P<0.05）;感兴趣区（脑干、皮层下,丘脑）FA值和MD值与CRS-R评分具有较好相关性,尤其是丘脑部。 结论DTI对于DOC影像学分级具有一定的临床参考价值。意识障碍程度越重,MD值越高,FA值越低。     

Resting-state EEG study of comatose patients: a connectivity and frequency analysis to find differences between vegetative and minimally conscious states

The aim of this study was to look for differences in the power spectra and in EEG connectivity measures between patients in the vegetative state (VS/UWS) and patients in the minimally conscious state (MCS). The EEG of 31 patients was recorded and analyzed. Power spectra were obtained using modern multitaper methods. Three connectivity measures (coherence, the imaginary part of coherency and the phase lag index) were computed. Of the 31 patients, 21 were diagnosed as MCS and 10 as VS/UWS using the Coma Recovery Scale-Revised (CRS-R). EEG power spectra revealed differences between the two conditions. The VS/UWS patients showed increased delta power but decreased alpha power compared with the MCS patients. Connectivity measures were correlated with the CRS-R diagnosis; patients in the VS/UWS had significantly lower connectivity than MCS patients in the theta and alpha bands. Standard EEG recorded in clinical conditions could be used as a tool to help the clinician in the diagnosis of disorders of consciousness.     

Cardiac autonomic responses to nociceptive stimuli in patients with chronic disorders of consciousness

Objectives

Patients with chronic disorders of consciousness (DOC) may show alterations of autonomic function; however, in this clinical population, no data are available on the specific effects of nociceptive stimuli on cardiac autonomic control. Thus, we aimed at investigating the effects of a noxious stimulation on heart rate variability (HRV) in a population of patients with chronic DOC, taking into account different states of consciousness (vegetative state/unresponsive wakefulness syndrome, VS/UWS and minimally conscious state, MCS).

Disentangling disorders of consciousness: Insights from diffusion tensor imaging and machine learning

Previous studies have suggested that disorders of consciousness (DOC) after severe brain injury may result from disconnections of the thalamo‐cortical system. However, thalamo‐cortical connectivity differences between vegetative state (VS), minimally conscious state minus (MCS?, i.e., low‐level behavior such as visual pursuit), and minimally conscious state plus (MCS+, i.e., high‐level behavior such as language processing) remain unclear. Probabilistic tractography in a sample of 25 DOC patients was employed to assess whether structural connectivity in various thalamo‐cortical circuits could differentiate between VS, MCS?, and MCS+ patients. First, the thalamus was individually segmented into seven clusters based on patterns of cortical connectivity and tested for univariate differences across groups. Second, reconstructed whole‐brain thalamic tracks were used as features in a multivariate searchlight analysis to identify regions along the tracks that were most informative in distinguishing among groups. At the univariate level, it was found that VS patients displayed reduced connectivity in most thalamo‐cortical circuits of interest, including frontal, temporal, and sensorimotor connections, as compared with MCS+, but showed more pulvinar‐occipital connections when compared with MCS?. Moreover, MCS? exhibited significantly less thalamo‐premotor and thalamo‐temporal connectivity than MCS+. At the multivariate level, it was found that thalamic tracks reaching frontal, parietal, and sensorimotor regions, could discriminate, up to 100% accuracy, across each pairwise group comparison. Together, these findings highlight the role of thalamo‐cortical connections in patients' behavioral profile and level of consciousness. Diffusion tensor imaging combined with machine learning algorithms could thus potentially facilitate diagnostic distinctions in DOC and shed light on the neural correlates of consciousness. Hum Brain Mapp 38:431–443, 2017 . © 2016 Wiley Periodicals, Inc.     

视觉威胁反应在判断严重意识障碍程度的应用

目的用强弱光源作为视觉威胁刺激物,与CRS-R量表中以手指为刺激物的视觉威胁反应进行对比,比较严重意识障碍患者对不同视觉威胁刺激物的敏感性差异;在此基础上研究视觉威胁反应能否作为意识的指标。方法随机选择89例严重意识障碍(DOC)患者,采用The JFK Coma Recovery Scale-Revise(JFK改进的昏迷恢复量表,以下简称CRS-R)对其进行床边测量。对于视觉威胁反应项,分别对患者采取手指、弱光、强光刺激物进行刺激,比较反应的差异。结果植物状态(VS)和最小意识状态(MCS)患者对手指视觉威胁刺激的反应具有显著的差异(P0.001),植物状态和最小意识状态患者对强光视觉威胁刺激的反应具有显著的差异(P0.001)。最小意识障碍患者对手指、强光两种视觉威胁刺激的反应没有显著性的差异(P0.05),植物状态患者对手指、强光两种视觉威胁刺激的反应没有显著性的差异(P0.05)。结论严重意识障碍患者(n=89)对不同刺激物(手指、弱光、强光)的反应无显著性差异;视觉威胁反应(手指和光)能反映意识。     

Prevalence of coma-recovery scale-revised signs of consciousness in patients in minimally conscious state

ABSTRACT

Different behavioural signs of consciousness can distinguish patients with an unresponsive wakefulness syndrome from patients in minimally conscious state (MCS). The Coma Recovery Scale-Revised (CRS-R) is the most sensitive scale to differentiate the different altered states of consciousness and eleven items detect the MCS. The aim of this study is to document the prevalence of these items. We analysed behavioural assessments of 282 patients diagnosed in MCS based on the CRS-R. Results showed that some items are particularly frequent among patients in MCS, namely fixation, visual pursuit, and reproducible movement to command, which were observed in more than 50% of patients. These responses were also the most probably observed items when the patients only showed one sign of consciousness. On the other hand, some items were rarely or never observed alone, e.g., object localisation (reaching), object manipulation, intelligible verbalisation, and object recognition. The results also showed that limiting the CRS-R assessment to the five most frequently observed items (i.e., fixation, visual pursuit, reproducible movement to command, automatic motor response and localisation to noxious stimulation) detected 99% of the patients in MCS. If clinicians have only limited time to assess patients with disorders of consciousness, we suggest to evaluate at least these five items of the CRS-R.     

慢性意识障碍合并脑积水的临床特征与疗效分析

目的探讨慢性意识障碍(DOC)合并脑积水的临床特征与治疗效果。方法回顾性分析首都医科大学三博脑科医院2014年1月—2017年12月收治的43例慢性意识障碍合并脑积水患者的临床资料。分析指标主要包括:病因、临床表现、影像学表现、意识障碍程度、发生脑积水的时间及治疗效果。结果在同期收治的120例慢性意识障碍患者中,43例患者(35.8%)被诊断为脑积水接受了分流手术治疗。本组患者中,导致脑积水的原发病因主要为颅脑创伤(18例,41.8%)和蛛网膜下腔出血(11例,25.6%);意识障碍为植物状态者11例(25.6%),最小意识状态者17例(39.5%)。脑积水患者初始症状多表现为意识下降(74.4%)、消化不良(58.1%)和肌张力增高(39.5%)。不同意识障碍程度的患者出现脑积水的时间也存在差异,严重患者(CRS-R评分<6分)脑积水主要发生在1个月内(72.8%);中度患者(CRS-R评分6~9分)和轻度患者(CRS-R评分>9分)患者多发生在4~12周,分别占60.9%和48.8%,但是不同组别差异无统计学意义(P=0.1003)。分流手术后患者症状多有不同程度的改善,其中CRS-R评分总体改善患者达77.4%,消化功能改善达75%,肌张力改善达55%。结论慢性意识障碍患者合并脑积水起病隐匿,无特殊临床表现;在影像学表现方面需与脑萎缩导致的脑室扩张鉴别。分流手术能在很大程度上改善脑积水的临床预后。     

Connectivity biomarkers can differentiate patients with different levels of consciousness

ObjectiveIn the present study, we searched for resting-EEG biomarkers that distinguish different levels of consciousness on a single subject level with an accuracy that is significantly above chance.MethodsWe assessed 44 biomarkers extracted from the resting EEG with respect to their discriminative value between groups of minimally conscious (MCS, N = 22) patients, vegetative state patients (VS, N = 27), and – for a proof of concept – healthy participants (N = 23). We applied classification with support vector machines.ResultsPartial coherence, directed transfer function, and generalized partial directed coherence yielded accuracies that were significantly above chance for the group distinction of MCS vs. VS (.88, .80, and .78, respectively), as well as healthy participants vs. MCS (.96, .87, and .93, respectively) and VS (.98, .84, and .96, respectively) patients.ConclusionsThe concept of connectivity is crucial for determining the level of consciousness, supporting the view that assessing brain networks in the resting state is the golden way to examine brain functions such as consciousness.SignificanceThe present results directly show that it is possible to distinguish patients with different levels of consciousness on the basis of resting-state EEG.     

Sleep patterns associated with the severity of impairment in a large cohort of patients with chronic disorders of consciousness

Objective

We assessed sleep patterns in 85 patients with chronic disorders of consciousness (DOC) in order to reveal any relationship with the degree of the impairment.

Behavioural and electrophysiological effects of tDCS to prefrontal cortex in patients with disorders of consciousness

ObjectivesLeft dorsolateral prefrontal cortex anodal transcranial direct current stimulation (tDCS) was applied in a group of patients with disorders of consciousness to determine the effects of modulation of spontaneous oscillatory brain activity.Methods12 patients in an unresponsive wakefulness syndrome (UWS) and 12 in a minimally conscious state (MCS) underwent 2-weeks active and 2-weeks sham tDCS. Neurophysiological assessment was performed with EEG power spectra and coherence analysis directly before and after each session.ResultsAn increase of power and coherence of the frontal and parietal alpha and beta frequency bands and significant clinical improvements were seen after the active tDCS in MCS patients. In contrast, UWS patients showed some local frontal changes in the slow frequencies. No treatment effect was observed after sham.ConclusionstDCS could induce changes in cortical EEG oscillations, modulating the travel of alpha and beta waves between anterior and posterior brain areas when some cognitive functions were preserved. This plays an important role in consciousness by integrating cognitive-emotional processing with the state of arousal. In unresponsive people, brain integration seems to be lost.SignificanceOur results further support the critical role of long-range fronto-parietal connections in consciousness and show the potential therapeutic utility of tDCS.     

CRS-R score in disorders of consciousness is strongly related to spectral EEG at rest

Patients suffering from disorders of consciousness still present a diagnostic challenge due to the fact that their assessment is mainly based on behavioral scales with their motor responses often being strongly impaired. We therefore focused on resting electroencephalography (EEG) in order to reveal potential alternative measures of the patient’s current state independent of rather complex abilities (e.g., language comprehension). Resting EEG was recorded in nine minimally conscious state (MCS) and eight vegetative state/unresponsive wakefulness syndrome (VS/UWS) patients. Behavioral assessments were conducted using the Coma-Recovery Scale—Revised (CRS-R). The signal was analyzed in the frequency domain and association between resting EEG and CRS-R score as well as clinical diagnosis were calculated using Pearson correlation and repeated-measures ANOVAs. The analyses revealed robust positive correlations between CRS-R score and ratios between frequencies above 8 Hz and frequencies below 8 Hz. Furthermore, the frequency of the spectral peak was also highly indicative of the patient’s CRS-R score. Concerning differences between clinical diagnosis and healthy controls, it could be revealed that while VS/UWS patients showed higher delta and theta activity than controls, MCS did not differ from controls in this frequency range. Alpha activity, on the other hand, was strongly decreased in both patient groups as compared to controls. The strong relationship between various resting EEG parameters and CRS-R score provides significant clinical relevance. Not only is resting activity easily acquired at bedside, but furthermore, it does not depend on explicit cooperation of the patient. Especially in cases where behavioral assessment is difficult or ambiguous, spectral analysis of resting EEG can therefore complement clinical diagnosis.     

Mirroring of a simple motor behavior in Disorders of Consciousness

ObjectiveIn patients suffering from Disorders of Consciousness (DOC) electrophysiological recordings at bedside could serve as a complimentary and economical tool to improve diagnosis. We utilized a motor observation and imagination paradigm to gain new insights on preserved cognitive processing in DOC.MethodsEEG brain oscillations were analyzed in 10 VS/UWS (Vegetative State/Unresponsive Wakefulness Syndrome) patients and 7 MCS (Minimally Conscious State) patients and 21 controls during observation and imagination of a grasping movement and group statistics were conducted.ResultsWhile control subjects showed a typical desynchronization at 8–15 Hz during observation of a movement, MCS patients presented an analogue response at 8–10 Hz, but exhibited a synchronization at 12–15 Hz. The VS group did not show a systematic response. Imagery-related activation was only sustained for 1500 ms even in control subjects, therefore, limiting conclusions regarding the ability to follow an instruction. Furthermore, a clinically diagnosed VS patient exhibited EEG responses indicative for MCS.ConclusionResults indicate that MCS patients are still able to process an observed motor behavior on a basic sensory and perhaps even pre-motoric level, but seem not to be capable of “mirroring” the movement like healthy participants.Significance“Real-world” tasks as presented here carry the potential to identify residual cognitive functioning in DOC patients and may ultimately help to lower misdiagnosis rates.     

The importance of polysomnography in the evaluation of prolonged disorders of consciousness: sleep recordings more adequately correlate than stimulus-related evoked potentials with patients’ clinical status

ObjectivesThe aim of our study was to evaluate the importance of sleep recordings and stimulus-related evoked potentials (EPs) in patients with prolonged disorders of consciousness (DOCs) by correlating neurophysiologic variables with clinical evaluation obtained using specific standardized scales.MethodsThere were 27 vegetative state (VS) and 5 minimally conscious state (MCS) patients who were evaluated from a clinical and neurophysiologic perspective. Clinical evaluation included the Coma Recovery Scale-Revised (CRS-R), Disability Rating Scale (DRS), and Glasgow Coma Scale (GCS). Neurophysiologic evaluation included 24-h polysomnography (PSG), somatosensory EPs (SEPs), brainstem auditory EPs (BAEPs), and visual EPs (VEPs).ResultsPatients with preservation of each single sleep element (sleep–wake cycle, sleep spindles, K-complexes, and rapid eye movement [REM] sleep) always showed better clinical scores compared to those who did not have preservation. Statistical significance was only achieved for REM sleep. In 7 patients PSG showed the presence of all considered sleep elements, and they had a CRS-R score of 8.29 ± 1.38. In contrast, 25 patients who lacked one or more of the sleep elements had a CRS-R score of 4.84 ± 1.46 (P < .05). Our multivariate analysis clarified that concurrent presence of sleep spindles and REM sleep were associated with a much higher CRS-R score (positive interaction, P < .0001). On the other hand, no significant associations were found between EPs and CRS-R scores.ConclusionsPSG recordings have proved to be a reliable tool in the neurophysiologic assessment of patients with prolonged DOCs, correlating more adequately than EPs with the clinical evaluation and the level of consciousness. The main contribution to higher clinical scores was determined by the concomitant presence of REM sleep and sleep spindles. PSG recordings may be considered inexpensive, noninvasive, and easy-to-perform examinations to provide supplementary information in patients with prolonged DOCs.     

Fronto-parietal coherence response to tDCS modulation in patients with disorders of consciousness

Aim of the study: A transcranial direct current stimulation (tDCS) protocol (20 min, 2 mA, anodal electrode at the left dorsolateral prefrontal cortex and cathodal electrode at the right supraorbital area) was applied in patients with different degrees of disorders of consciousness (DoC). Although previous research indicates that it could improve patients’ coma recovery scale-revised (CRS-R) scores, the brain's electrophysiological responses to tDCS are still unclear. Therefore, the present study was performed to explore the underlying brain responses of patients in a minimally conscious state (MCS) and an unresponsive wakefulness syndrome (UWS) to tDCS modulation.

Materials and methods: Seventeen patients with DoC were recruited in a sham controlled crossover study receiving real and sham tDCS. EEG coherence was used to measure functional connectivity changes induced by the tDCS modulation.

Results: After real tDCS modulation, the fronto-parietal coherence significantly increased in the theta band and decreased in the gamma band in the MCS group. No significant changes were found in the UWS group. The coherence responses significantly correlated with the patients’ baseline CRS-R scores. No distinct alteration occurred in the sham session for either the MCS or UWS patients.

Conclusions: The coherence responses to the present tDCS protocol may be a tool for diagnosing MCS versus UWS, as they may be a crucial cause of the different clinical effects in the two states.     

The influence of high-frequency repetitive transcranial magnetic stimulation on endogenous estrogen in patients with disorders of consciousness

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been proposed as a promising therapeutic intervention for neurological disorders. However, the precise mechanisms of rTMS in neural excitability remains poorly understood. Estradiol is known to have strong influence on cortical excitability. This study aimed to determine whether high-frequency (HF) rTMS influences endogenous estradiol in male patients with disorders of consciousness (DOC).MethodsA randomized controlled trial was conducted with a total of 57 male patients with DOC. Eventually, 50 patients completed the study. Twenty-five patients underwent real rTMS, and 25 patients underwent sham rTMS, which were delivered over the dorsolateral prefrontal cortex. The primary outcome measure was the change in serum estradiol from baseline to after 10 sessions of HF-rTMS. The improvement in the total score of the JFK Coma Recovery Scale-Revised (CRS-R) was also assessed.ResultsChanges in estradiol levels and CRS-R scores from pre-to post-treatment were significantly different between the active rTMS and sham stimulation conditions. A significant enhancement of CRS-R scores in the patients receiving rTMS stimulation was observed compared to the sham group. Serum estradiol levels in patients following HF-rTMS were significantly higher than their baseline levels, whereas no significant changes were found in the sham group from pre-to post-stimulation. The rise in estradiol levels was greater in responders than in non-responders. The changes in estradiol levels were significantly positively correlated with the improvement in CRS-R scores.ConclusionThese preliminary findings indicate that serum estradiol levels are affected by HF-rTMS and positively related to clinical responses in male patients with DOC. The elevation of estradiol levels may lay a physiological foundation for successful rTMS treatment for DOC patients by increasing cortical excitability.     

脑室线性结构变化与严重意识障碍疾病的相关性研究

目的评价脑室线性结构在意识障碍(DOC)患者诊断和分级中的应用价值。方法收集2015年1月至2015年12月就诊于中国人民解放军陆军总医院的20例DOC患者,由两名主治医师根据CRS-R评分量表将患者分为无反应觉醒综合征组(UWS)和微意识状态组(MCS)。另选10例健康志愿者作为对照组。分析患者MRI T_1图像的结果,测量数据并探索这些测量指标与CRS-R评分之间的相关性。结果 UWS组和MCS组的Huckman值和第三脑室宽度明显高于对照组(均P0.05),而PDI指数和脑室指数则低于对照组(均P0.05),除Evans值外其余各指标在UWS组和MCS组之间差别也具有统计学意义(均P0.05)。Huckman值和第三脑室宽度与CRS-R评分呈负相关,而PDI指数和脑室指数则相反。结论脑室线性结构测量可以用于DOC患者意识水平的评估。     

脑机接口技术在慢性意识障碍诊疗中的应用进展

慢性意识障碍(DOC)包括植物状态(VS)或无反应觉醒综合征(UWS)和微意识状态(MCS),目前临床鉴别诊断以及治疗仍是难题。慢性意识障碍评估,目前临床使用较多的是量表,但存在误判。为了提高诊断准确率,出现一些基于神经影像学的辅助检测方法,如脑机接口(BCI)技术。BCI主要通过脑电信号的处理用人机对话的方法检测患者是否存在指令跟随,被用于意识障碍患者意识状态的检测及康复治疗的评价。本文简述BCI技术特点及在慢性意识障碍中的应用前景。     

Effect of High-Frequency Repetitive Transcranial Magnetic Stimulation on Brain Excitability in Severely Brain-Injured Patients in Minimally Conscious or Vegetative State

BackgroundRepetitive transcranial magnetic stimulation (rTMS) induces prolonged functional changes in the cerebral cortex in normal conditions and in altered states of consciousness. Its therapeutic effects have been variously documented.ObjectiveThe aim of this study was to investigate the reactivity of electroencephalography (EEG) and the clinical response in six severely brain-injured patients in an altered state of consciousness (minimally conscious state [MCS] or vegetative state [VS]). EEG rhythm and brain excitability were measured before and after a protocol of high-frequency rTMS.MethodsAll six patients underwent clinical and neurophysiological evaluation before rTMS and immediately thereafter. EEG data in resting state were acquired at the beginning of the exam (T₀), after rTMS (T₁), and 38 min after rTMS (T₂). From these data the power values were computed using Fast Fourier Transform.ResultsrTMS over the motor cortex induced long-lasting behavioral and neurophysiological modifications in only one patient in MCS. No significant clinical or EEG modifications were detected in any of the other patients, except for changes in motor threshold and motor evoked potential amplitude over the stimulated motor areas.ConclusionsThe main finding of the study is the correlation between EEG reactivity and clinical response after rTMS. Reappearance of fast activity and an increase in slow activity were noted in the one patient with transitory arousal, whereas no significant reliable changes were observed in the other patients showing no clinical reactivity.     

Evolution of psychological condition in caregivers of patients with disorders of consciousness: a longitudinal study

The aim of this study is to evaluate mood disorders and needs in caregivers of disorders of consciousness (DOC) patients during the admission to Neurorehabilitation Unit. A total of 80 caregivers was enrolled and divided in two groups (caregivers of vegetative state–VS patients and caregivers of minimally conscious state–MCS patients). Paired sample t tests were carried out to test differences between baseline observation (T0) and after 6 months (T1). Caregivers of VS patients showed an improvement between T0 and T1 especially, in vitality, mean health, Beck Depression Inventory (BDI-II), Spielberger State-Trait Anxiety Inventory-Y (STAI-Y), Prolonged Grief Disorder (PG 12) and Caregiver Needs Assessment (CNA). On the other hand, caregivers of MCS patients showed a significant improvement in: BDI II, STAI Y and CNA. These data confirmed that the presence of psychological problems, the quality of life and the psychological wellbeing of caregivers of DOC patients improved over the time.     

最小意识状态的定义、诊断标准及临床鉴别

最小意识状态可由急性脑损伤后昏迷或植物状态、变性或先天性神经系统疾病发展而来，有严重意识障碍，但病人既不符合昏迷也不符合植物状态的诊断，存存部分意识鉴别最小意识状态、昏迷及植物状态对于预后的判定有重要的意义。本文主要综述最小意识状念的定义、诊断标准、鉴别诊断及有关临床意义。