重复经颅磁刺激对慢性意识障碍患者的促醒治疗研究

目的 探讨重复经颅磁刺激（rTMS）调控楔前叶对慢性意识障碍患者意识恢复的影响。方法 选取郑州大学第五附属医院神经外科2020年6月—2021年5月收治的慢性意识障碍患者11例,在常规治疗基础上应用楔前叶10 Hz rTMS治疗,单次刺激时间为14 min,每日2次,持续14 d,共28次。记录rTMS治疗前（T0）、治疗后（T1）及治疗结束后1个月（T2）的昏迷恢复量表修订版（CRS-R）评分;同时记录T0及T1时静息态脑电,分别使用频谱分析及功能连接性分析方法提取不同脑区脑电不同频段的能量及相干性。结果 与T0时相比,CRS-R评分在T1、T2时均提高（P<0.05）;额区alpha频段和顶区beta频段的能量在T1时提高,差异有统计学意义（P<0.05）;额-中央-顶区alpha和beta频段的相干性在T1时增强,差异有统计学意义（P<0.05）。结论 重复经颅磁刺激调控楔前叶能促进慢性意识障碍患者的意识恢复。重复经颅磁刺激调控楔前叶对慢性意识障碍患者静息态脑电产生的积极改变有助于解释意识恢复的神经机制。[国际神经病学神经外科学杂志, 2022, 49(2):5...     

Transcranial direct current stimulation in disorders of consciousness: a review

It is a challenge to evaluate and treat the patients with disorders of consciousness (DOC) in the clinic. Due to the huge costs of prolonged intensive care, the management of these patients raises great financial strain on families and important ethical questions. To date, several studies have attempted to specifically detect pharmacologic or non-pharmacologic effectiveness, and until now, there are no evidence-based guidelines about the treatment of patients with DOC. Recently, because of ethical and procedural limitations on the use of invasive stimulation techniques, non-invasive brain stimulation, such as the transcranial direct current stimulation (tDCS), has been investigated for improving the level of consciousness in patients with DOC. This paper briefly reviewed the key clinical investigations using tDCS with the aim of better understanding the pathophysiological mechanism of DOC or improving the level of consciousness in patients with DOC. In conclusion, some beneficial results of tDCS protocols have been shown in patients with DOC, especially targeting the left dorsolateral prefrontal cortex in minimally conscious state. However, these investigations must be continued in larger controlled, randomized, blinded and prospective studies in order to transpose these preliminary data to clinical effects. Furthermore, an encouraging perspective for the future is the combination of neurophysiological or functional neuroimaging techniques with non-invasive brain stimulation to evaluate neuro-modulatory effects of stimulation in patients with DOC.     

颅脑外伤后微意识状态重复经颅磁刺激促醒治疗的研究

目的探讨左侧额叶背外侧区的高频重复经颅磁刺激治疗颅脑外伤后微意识状态的效果和安全性。方法将中国人民解放军总医院第七医学中心神经外科2015年12月—2016年9月收治的颅脑外伤后微意识状态患者32例,分为经颅磁刺激治疗组(磁刺激组)和对照组;磁刺激组患者接受经颅磁刺激治疗,对照组患者在同样的时间段内接受假刺激。疗效评价指标为治疗前后昏迷恢复量表修订版(CRS-R)评分的变化(组间对比,基线与治疗终点对比)。结果磁刺激组患者意识改善率为64.7%,对照组意识改善率为13.3%。治疗终点与基线对比,磁刺激组CRS-R评分提升明显,对照组CRS-R评分无明显提升。所有患者在治疗全程中无不良事件发生。结论左侧额叶背外侧区重复经颅磁刺激治疗对颅脑外伤后微意识状态患者有较为明确的促醒调控作用,并且该治疗安全。     

Neurobehavioural assessment and diagnosis in disorders of consciousness: a preliminary study of the Sensory Tool to Assess Responsiveness (STAR)

The Sensory Tool to Assess Responsiveness (STAR) is an interdisciplinary neurobehavioural diagnostic tool for individuals with prolonged disorders of consciousness. It utilises current diagnostic criteria and is intended to improve upon the high misdiagnosis rate in this population. This study assesses the inter-rater reliability of the STAR and its diagnostic validity in comparison with the Coma Recovery Scale–Revised (CRS-R) and the Wessex Head Injury Matrix (WHIM). Participants were patients with severe acquired brain injury resulting in a disorder of consciousness, who were admitted to the Royal Leamington Spa Rehabilitation Hospital between 1999 and 2009. Patients underwent sensory stimulation sessions during their period of admission, which were recorded on video. Using this footage, patients were re-assessed for this study using the STAR, WHIM and CRS-R criteria. The STAR demonstrated “moderate” inter-rater reliability, “substantial” diagnostic agreement with the CRS-R, and “moderate” agreement with the WHIM. There were no significant differences between diagnoses assigned by the different assessments. The STAR demonstrated a good degree of inter-rater reliability in identification of diagnoses for patients with disorders of consciousness. The diagnostic outcomes of the STAR agreed at a good level with the CRS-R, moderately with the WHIM, and did not significantly differ from either. This demonstrates the reliability and validity of the STAR, showing its appropriateness for clinical use. Future longitudinal studies and research into the STAR's applicability in long-stay rehabilitation are indicated.     

Transient tinnitus suppression induced by repetitive transcranial magnetic stimulation and transcranial direct current stimulation

Modulation of activity in the left temporoparietal area (LTA) by 10 Hz repetitive transcranial magnetic stimulation (rTMS) results in a transient reduction of tinnitus. We aimed to replicate these results and test whether transcranial direct current stimulation (tDCS) of LTA could yield similar effect. Patients with tinnitus underwent six different types of stimulation in a random order: 10-Hz rTMS of LTA, 10-Hz rTMS of mesial parietal cortex, sham rTMS, anodal tDCS of LTA, cathodal tDCS of LTA and sham tDCS. A non-parametric analysis of variance showed a significant main effect of type of stimulation ( P  = 0.002) and post hoc tests showed that 10-Hz rTMS and anodal tDCS of LTA resulted in a significant reduction of tinnitus. These effects were short lasting. These results replicate the findings of the previous study and, in addition, show preliminary evidence that anodal tDCS of LTA induces a similar transient tinnitus reduction as high-frequency rTMS.     

高颈段脊髓电刺激治疗重度意识障碍的疗效分析

目的探讨高颈段脊髓电刺激（spinal cord stimulation,SCS）对重度意识障碍病人的促醒疗效。方法回顾性分析22例重度意识障碍病人的临床资料,其中植物状态8例,最小意识状态14例。病人在原发病急性期后3个月接受电生理评估,15例病人在满足电生理评估标准后接受高颈段SCS治疗,余9例未接受治疗。结果所有病人随访9个月,接受SCS治疗的15例病人中清醒9例,GOS评分：轻度残疾2例,中度残疾2例,重度残疾5例;刺激后脑血流量较刺激前增加了36．6％（t=2．775,P〈0．05）。未接受SCS治疗的病人均未清醒。结论高颈段SCS是治疗重度意识障碍病人较为适合的方法。     

Transcranial direct current stimulation in psychiatric disorders

The interest in non-invasive brain stimulation techniques is increasing in recent years. Among these techniques, transcranial direct current stimulation (tDCS) has been the subject of great interest among researchers because of its easiness to use, low cost, benign profile of side effects and encouraging results of research in the field. This interest has generated several studies and randomized clinical trials, particularly in psychiatry. In this review, we provide a summary of the development of the technique and its mechanism of action as well as a review of the methodological aspects of randomized clinical trials in psychiatry, including studies in affective disorders, schizophrenia, obsessive compulsive disorder, child psychiatry and substance use disorder. Finally, we provide an overview of tDCS use in cognitive enhancement as well as a discussion regarding its clinical use and regulatory and ethical issues. Although many promising results regarding tDCS efficacy were described, the total number of studies is still low, highlighting the need of further studies aiming to replicate these findings in larger samples as to provide a definite picture regarding tDCS efficacy in psychiatry.     

Long‐term functional prognosis and related factors of spinal cord stimulation in patients with disorders of consciousness

IntroductionThe treatment of patients with disorders of consciousness (DoC) remains a challenging issue, and spinal cord stimulation (SCS) has been reported to be a promising treatment for DoC in some studies.AimsThis study explores the efficiency of SCS in treating patients with DoC at different consciousness levels, including the vegetative state/unresponsive wakefulness syndrome (VS/UWS) and the minimally conscious state (MCS) and summarizes and analyzes the long‐term effect and related factors of SCS in patients with DoC.ResultsAn overall positive outcome was reached in 35 of 110 patients (31.8%). Among patients with positive outcomes, the MCS group improved 45.53% more than VS/UWS group, and this difference was statistically significant. In terms of the recommendation standard, positive outcomes occurred in 33 patients (94.3%) in the highly recommended group and 2 patients (5.7%) in the weakly recommended group (p < 0.001). After adjustment for potential covariables, young age (age ≤ 19 years old) (p = 0.045) and MCS (p < 0.001) were significantly correlated with positive outcome. A nomogram based on age, state of consciousness, and pathogeny showed good predictive performance, with a c‐index of 0.794. The Hosmer–Lemeshow goodness‐of‐fit test showed that the model was well calibrated (χ ² = 3.846, p = 0.871).ConclusionsSCS is one of the most feasible treatments for patients with DoC, especially for patients with MCS. Younger age is significantly associated with better outcomes and could therefore serve as a basis for preoperative screening. However, more evidence‐based randomized controlled trials are needed to confirm the efficacy of the treatment.     

Repetitive transcranial magnetic stimulation (rTMS) versus transcranial direct current stimulation (tDCS) in the management of patients with fibromyalgia: A randomized controlled trial

ObjectivesThe aim of this study was to compare the effects of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) on pain and quality of life in patients with fibromyalgia.MethodsThirty participants were randomized into two groups of 15 patients, to receive 3 sessions of either high-frequency (10 Hz) rTMS or 2 mA, 20 min anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex (DLPFC) over 1 week. Pain was assessed using a Visual Analog Scale (VAS) before treatment, immediately after treatment, 6 and 12 weeks later. Quality of life was evaluated using the Revised Fibromyalgia Impact Questionnaire (FIQR) and psychiatric symptoms were measured using the Depression Anxiety Stress Scale-21 Item (DASS-21) before treatment, and 6 and 12 weeks after treatment.ResultsFor the VAS there was a significant time-group interaction, showing that the behavior of two groups differed regarding changes of VAS in favor of the RTMS group (df = 1.73, F = 4.80, p = <0.016). Time-group interaction effect on DASS-21 and FIQR was not significant. 66.6% of patients in rTMS group and 26.6% of patients in tDCS group experienced at least a 30% reduction of VAS from baseline to last follow-up (p = 0.028).DiscussionWith the methodology used in this study, both rTMS and tDCS were safe modalities and three sessions of rTMS over DLPFC had greater and longer lasting analgesic effects compared to tDCS in patients with FM. However, considering the limitations of this study, further studies are needed to explore the most effective modality.     

Vegetative state, minimally conscious state, akinetic mutism and Parkinsonism as a continuum of recovery from disorders of consciousness: an exploratory and preliminary study

The aim of this study was to review the usefulness of clinical and instrumental evaluation in individuals with disorders of consciousness (DOC). Thirteen subjects with severe acquired brain injury (ABI) and a diagnosis of DOC were evaluated using the Coma Recovery Scale in its revised version (CRS-R) and a new global disability index, the Post-Coma Scale (PCS). These instruments were administered both by a neutral examiner (professional) and by a professional in the presence of a caregiver. All patients were also scored using the International Classification of Functioning, Disability and Health (ICF). A statistically significant correlation between CRS-R and PCS was demonstrated. However, there also emerged significant differences in responsiveness between professional versus caregiver+professional assessment using the two scales. The emotional stimulation provided by significant others (caregivers) during administration of DOC evaluation scales may improve the assessment of responsiveness.     

Visual cognition in disorders of consciousness: From V1 to top‐down attention

What is it like to be at the lower boundaries of consciousness? Disorders of consciousness such as coma, the vegetative state, and the minimally conscious state are among the most mysterious and least understood conditions of the human brain. Particularly complicated is the assessment of residual cognitive functioning and awareness for diagnostic, rehabilitative, legal, and ethical purposes. In this article, we present a novel functional magnetic resonance imaging exploration of visual cognition in a patient with a severe disorder of consciousness. This battery of tests, first developed in healthy volunteers, assesses increasingly complex transformations of visual information along a known caudal to rostral gradient from occipital to temporal cortex. In the first five levels, the battery assesses (passive) processing of light, color, motion, coherent shapes, and object categories (i.e., faces, houses). At the final level, the battery assesses the ability to voluntarily deploy visual attention in order to focus on one of two competing stimuli. In the patient, this approach revealed appropriate brain activations, undistinguishable from those seen in healthy and aware volunteers. In addition, the ability of the patient to focus one of two competing stimuli, and switch between them on command, also suggests that he retained the ability to access, to some degree, his own visual representations. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Noninvasive cortical stimulation with transcranial direct current stimulation in Parkinson's disease.

Electrical stimulation of deep brain structures, such as globus pallidus and subthalamic nucleus, is widely accepted as a therapeutic tool for patients with Parkinson's disease (PD). Cortical stimulation either with epidural implanted electrodes or repetitive transcranial magnetic stimulation can be associated with motor function enhancement in PD. We aimed to study the effects of another noninvasive technique of cortical brain stimulation, transcranial direct current stimulation (tDCS), on motor function and motor-evoked potential (MEP) characteristics of PD patients. We tested tDCS using different electrode montages [anodal stimulation of primary motor cortex (M1), cathodal stimulation of M1, anodal stimulation of dorsolateral prefrontal cortex (DLPFC), and sham-stimulation] and evaluated the effects on motor function--as indexed by Unified Parkinson's Disease Rating Scale (UPDRS), simple reaction time (sRT) and Purdue Pegboard test--and on corticospinal motor excitability (MEP characteristics). All experiments were performed in a double-blinded manner. Anodal stimulation of M1 was associated with a significant improvement of motor function compared to sham-stimulation in the UPDRS (P < 0.001) and sRT (P = 0.019). This effect was not observed for cathodal stimulation of M1 or anodal stimulation of DLPFC. Furthermore, whereas anodal stimulation of M1 significantly increased MEP amplitude and area, cathodal stimulation of M1 significantly decreased them. There was a trend toward a significant correlation between motor function improvement after M1 anodal-tDCS and MEP area increase. These results confirm and extend the notion that cortical brain stimulation might improve motor function in patients with PD.     

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。     

Noninvasive remote activation of the ventral midbrain by transcranial direct current stimulation of prefrontal cortex

The midbrain lies deep within the brain and has an important role in reward, motivation, movement and the pathophysiology of various neuropsychiatric disorders such as Parkinson''s disease, schizophrenia, depression and addiction. To date, the primary means of acting on this region has been with pharmacological interventions or implanted electrodes. Here we introduce a new noninvasive brain stimulation technique that exploits the highly interconnected nature of the midbrain and prefrontal cortex to stimulate deep brain regions. Using transcranial direct current stimulation (tDCS) of the prefrontal cortex, we were able to remotely activate the interconnected midbrain and cause increases in participants'' appraisals of facial attractiveness. Participants with more enhanced prefrontal/midbrain connectivity following stimulation exhibited greater increases in attractiveness ratings. These results illustrate that noninvasive direct stimulation of prefrontal cortex can induce neural activity in the distally connected midbrain, which directly effects behavior. Furthermore, these results suggest that this tDCS protocol could provide a promising approach to modulate midbrain functions that are disrupted in neuropsychiatric disorders.