功能神经外科主要疾病的治疗策略与展望

随着电生理技术、神经影像学、立体定向与神经调控技术的发展,功能神经外科疾病的诊疗范畴不断地深入与扩大,已成为发展最迅速、最有活力以及最具前景的分支学科之一。功能性神经外科疾病主要包括癫痫、运动障碍性疾病、颅神经疾患、痉挛状态、周围神经外科疾病以及顽固性疼痛等。本文主要围绕以上疾病的外科治疗策略和展望作一述评。     

立体定向技术和神经调控技术与功能神经外科的现状

随着神经影像学、神经电生理、立体定向以及神经调控技术的广泛临床应用,功能神经外科疾病的诊治水平有了较快发展,手术定位从影像学解剖定位发展到神经电生理学的定位,立体定向设备从立体定向仪发展到神经导航设备,手术入路的设计从手工计算手术轨迹到计算机设计的手术计划系统,手术方式从脑深部核团立体定向毁损术到神经电刺激技术,促进了功能神经外科向纵深发展.     

帕金森病的干细胞移植及其基因治疗研究进展

随着神经干细胞研究的发展以及分子生物学技术的进步，神经干细胞移植及基因治疗已成为帕金森病治疗的主要研究方向。本文回顾了帕金森病的治疗现状、移植神经干细胞的来源、相关的修复机制及神经干细胞联合基因治疗帕金森病的进展作一综述。     

大脑皮质下结构与癫痫

随着神经电生理学、神经影像学等技术的快速发展,已有大量证据显示癫痫的发生发展与皮质-皮质下神经网络密切相关。本文拟就丘脑、下丘脑、小脑、基底节、脑干等皮质下结构参与癫痫发生发展的相关研究,以及目前神经调控治疗耐药性癫痫所针对的重要皮质下神经核团靶点进行综述,以为发掘癫痫治疗新靶点提供帮助。     

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。     

神经电生理监护在颅神经微血管减压术中的应用

随着电生理技术的不断发展，其与神经外科手术的联系越来越密切。近十年来，术中电生理监护得到广泛应用，其中包括神经肌电图、脑电图、诱发电位、脑磁图等。微血管减压（microvessel decompression，MVD）术作为功能神经外科的重要组成部分，目前相关技术趋向成熟，而面肌肌电图和脑干听觉诱发电位有助于加强其术中颅神经保护、疗效判断以及术后神经功能评估。本文从神经电生理原理、操作技术和影响因素以及在MVD术中应用价值，结合文献进行综述。     

神经介入治疗过程中并发症的防治

神经介入治疗学是随着近代神经影像学技术以及介入材料工程学的进展而建立和发展起来的新兴学科。由于脑血管病是神经内外科最常见的疾病之一，故神经介入治疗的应用范围非常广泛。目前，除北京、天津、上海、广州、武汉等大城市已相继建立了神经介入治疗中心外，其他中、小城市也在纷纷开展神经介入治疗工作。在国内从事神经介入治疗的医师中，多数为神经外科医师，     

神经内镜技术在神经外科中的应用

近年来随着医学科学技术的发展和神经内镜的开发研制，神经内镜技术已被众多的神经外科医师所接受。在欧美和日本等发达国家，神经内镜技术开展的较早，每年都有很多关于神经内镜技术的培训班和学术交流；而我国神经内镜技术的应用起步虽相对较晚，但发展很快，目前国内已有数百家医院购置了神经内镜的仪器设备，并在神经外科临床不同的方面开展了此项工作，而且也取得了可喜的成绩。     

超选择性动脉内灌注罂粟硷治疗蛛网膜下腔出血后脑血管痉挛

随着介入神经放射技术的日趋发展,一种治疗外周型脑血管痉挛的最新方法便应运而生。文章重点介绍超选择性动脉内灌注罂粟硷,治疗脑血管痉挛的方法以及它的适应症、禁忌症、机理和疗效。     

交通性脑积水的神经内镜诊治进展

正对交通性脑积水(communicating hydrocephalus,CHC)的认识,一直处于不断更新和发展的过程中,因此,对CHC的诊治也是在不断的发展和进步中。湍流理论下的CHC,首选分流术,尤其是脑室-腹腔分流术(ventriculoperitoneal shunt,VPS),但并发症发生率较高。随着对CHC认识的深入,以及神经内镜技术进步,神经内镜对CHC的诊治地位日益提高,     

睡眠脑电成分对慢性意识障碍患者评估及预后预判的研究

目的通过监测意识障碍（DOC）患者的脑电,分析患者治疗前后脑电背景活动及其特征性波形,比较不同意识水平以及不同预后患者在脑电成分上的差异,探寻DOC患者的脑电活动规律和睡眠期脑电活动的特征。 方法收集自2020年1月至4月北京大学国际医院神经外科收治的6例DOC患者,采集患者治疗前后的修订版昏迷恢复量表评分,以及16 h以上的长程视频脑电图监测,分析DOC患者的脑电活动特征、睡眠脑电周期及成分。 结果不同意识水平的患者均有可能出现枕区α节律,健侧为优势侧,睁眼时均未被抑制;但意识水平好的患者更有可能出现枕区α节律,预后较好的患者更有可能出现睡眠纺锤波。 结论DOC患者是否出现枕区α节律以及是否出现特征性的睡眠脑电成分对意识水平及预后具有一定的提示意义,睡眠脑电活动的周期性有待进一步研究,对DOC患者的临床治疗节律调节及睡眠意识相关性理解有一定的参考意义。     

Changes of salt intake and of (Na+K)-ATPase activity in brain after high dose treatment with deoxycorticosterone

Mineralocorticoids (MC) have a dual effect on salt intake: in adrenalectomized rats, they reduce previously elevated salt intake; and in intact rats a high MC dose increases salt intake. We have studied the activity of (Na+K)-ATPase and [3H]ouabain binding in rats treated with deoxycorticosterone (DOC) in doses that elicited a salt appetite. Brains were removed from control and treated animals, and 20 different areas were punched out from brain slices cut every 300 microns. DOC treatment significantly reduced (Na+K)-ATPase activity in the lateral hypothalamic area, anterior amygdaloid and lateral amygdaloid nuclei, while increasing it in the periventricular gray matter; changes in other regions were not significant. Binding of [3H]ouabain was not modified by DOC treatment. In parallel experiments, we determined MC receptors in adrenalectomized rats. Binding of [3H]aldosterone was preferentially found in hippocampus, followed by lateral septum, anterior, posterior and lateral amygdaloid areas, with lower levels in other regions. However, there was no correlation between [3H]aldosterone binding and (Na+K)-ATPase activity in brain punches from either control or DOC-treated rats. Further experiments are needed to ascertain if (Na+K)-ATPase changes in discrete areas of the brain containing moderate levels of mineralocorticoid receptors, are related to the behavioral effects of DOC.     

Dose-, time-, age-, and sex-response profiles for the anticonvulsant effects of deoxycorticosterone in 15-day-old rats

Recently, we have shown that a single high dose of the adrenal steroid precursor hormone deoxycorticosterone (DOC) has potent anticonvulsant effects in 15-day-old rats. To better define the actions of DOC, the present study established dose-, time-, age-, and sex-response curves for the anticonvulsant actions of DOC. Methods. Dose- and time-response studies were done using two different seizure models: (1) maximal pentylenetetrazol seizures (MMT) and (2) maximal electroconvulsive shock (MES) seizures. Subsequently, age- and sex-response studies were done using MMT seizures and two different DOC doses, one low (nonsedating) and one high (sedating). Results. In dose-response studies, DOC suppressed MMT seizures with an ED(50) of about 5 mg/kg (sc). Higher doses were necessary to suppress MES seizures, where the ED(50) was about 20 mg/kg. In time-response studies, DOC's effects were rapid in onset. Complete suppression of seizures was seen by 5 min in the MES model and by 15 min in the MMT model. In developmental studies, both a low nonsedating and a high sedating dose of DOC suppressed MMT seizures in neonatal, infant, weanling, and juvenile rats of either sex. The suppressive effects of low-dose DOC were lost after puberty, however. The suppressive effects of high-dose DOC also declined after puberty, especially in males. Conclusion. DOC has significant anticonvulsant actions that occur in prepubertal, but not postpubertal subjects. DOC might have clinical importance in the future treatment of childhood seizure disorders.     

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.     

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.     

Is there anybody in there? Detecting awareness in disorders of consciousness

The bedside detection of awareness in disorders of consciousness (DOC) caused by acquired brain injury is not an easy task. For this reason, differential diagnosis using neuroimaging and electrophysiological tools in search for objective markers of consciousness is being employed. However, such tools cannot be considered as diagnostic per se, but as assistants to the clinical evaluation, which, at present, remains the gold standard. Regarding therapeutic management in DOC, no evidence-based recommendations can be made in favor of a specific treatment. The present review summarizes clinical and paraclinical studies that have been conducted with neuroimaging and electrophysiological techniques in search of residual awareness in DOC. We discuss the medical, scientific and ethical implications that derive from these studies and we argue that, in the future, the role of neuroimaging and electrophysiology will be important not only for the diagnosis and prognosis of DOC but also in establishing communication with these challenging patients.     

Is the Mineralocorticoid Receptor in Brown Norway Rats Constitutively Active?

In a previous study using corticosterone treatment of adrenalectomized rats, we hypothesized that mineralocorticoid receptor (MR)-related mechanisms are constitutively active and that glucocorticoid receptor (GR)-mediated mechanisms are more efficient in Brown Norway rats compared to Fischer 344 (F344) rats. In order to discriminate the mineralocorticoid from the glucocorticoid actions exerted by corticosterone, F344 and Brown Norway adrenalectomized rats were treated with increasing doses (1, 5 and 25 microg/ml of drinking water) of deoxycorticosterone (DOC, MR-specific ligand) or RU 28362 (GR-specific ligand). These rats were compared with long-term adrenalectomized (ADX) untreated rats and sham-ADX rats. This study confirms our previous results, notably the lack of effect of ADX on body weight and fluid intake in Brown Norway rats. Moreover, DOC treatment had no effect in Brown Norway rats whereas the higher dose restored fluid intake of the F344 ADX group to sham values. These results support the hypothesis of a constitutive activation of the MR and therefore the insensitivity of this receptor to its ligand in Brown Norway rats. Alternatively, RU 28362 treatment induced greater weight loss, decrease in food intake, anxiolysis, thymus involution, and decrease in plasma transcortin concentration and pituitary corticosteroid receptor densities in Brown Norway rats than in F344 rats, which is consistent with greater efficiency of GR mechanisms in Brown Norway rats than in F344 rats. Therefore, these strains are of great utility to disentangle MR and GR effects on complex phenotypes.     

Bromocriptine prevents neuron damage following inhibition of superoxide dismutase in cultured ventral spinal cord neurons

Abstract

Rpsen et al. have reported point mutations in the cytosolic Cu/Zn superoxide dismutase (SOD 1) gene in some families with familial amyotrophic lateral sclerosis (ALS). To determine whether decreased SOD activity could contribute to neuronal damage, rat embryo ventral spinal cord neurons were incubated with diethyldithiocarbamate (DOC), an inhibitor of SOD. There was a marked increase in neuronal damage in cultures exposed to DOC and this phenomenon was dose-related. In this paradigm, these deteriorative changes were prevented by bromocriptine. DOC-treated ventral spinal cord neurons provide an in vitro model of free radical neurotoxicity secondary to decreased SOD activity. Simultaneous treatment with bromocriptine and DOC reduced neurotoxicity, indicating that bromocriptine has a neuroprotective effect against free radicals. [Neural Res 1997; 19: 389-392]     

Current Status of Neuromodulatory Therapies for Disorders of Consciousness

Treatment for disorders of consciousness (DOCs) is still a Gordian knot. Evidence-based guidelines on the treatment of DOC patients are not currently available, while neuromodulation techniques are seen as a potential treatment. Multiple neuromodulation therapies have been applied. This article reviews the most relevant studies in the literature in order to describe a clear picture of the current state of neuromodulation therapies that could be used to treat DOC patients. Both invasive and non-invasive brain stimulation is discussed. Significant behavioral improvements in prolonged DOCs under neuromodulation therapies are rare. The efficacy of various such therapies remains a matter of debate. Further clinical investigations of existing techniques in larger samples properly controlling for spontaneous recovery are needed, and new approaches are awaited.