Heart rate variability in brain death

The sensitivity and specificity of heart rate variability (HRV) in the corroboration of brain death diagnosis in patients with acute traumatic intracranial lesions was evaluated in 20 patients with clinical criteria of brain death, nine patients in deep coma (Glasgow scale <7) and 18 normal controls, all age matched. The electrocardiogram was sampled at 650 Hz and several parameters of HRV were calculated, in both time and frequency domains. The HRV parameters were significantly lower in the brain death group compared with the deep coma group. Linear discriminant analysis between brain death and deep coma patients was performed on a data set made of nine randomly selected patients with clinical criteria of brain death and nine patients in deep coma. Cross-validation was performed on the remaining 11 patients with clinical criteria of brain death. All patients in the data set were correctly classified (sensitivity and specificity of 100%). All patients in the cross-validation set were correctly classified (sensitivity of 100%). Further studies are necessary to evaluate the specificity of the method in the independent set of deep coma patients and in the follow-up of comatose and vegetative patients to identify irreversibility of HRV. Nevertheless, these results suggest that HRV analysis constitutes a fully sensitive and specific method for assessing brain death in potential organ donors with acute traumatic lesions of the brain. This fast, quantitative and bedside method seems very promising for the early confirmation of brain death, which is an important factor for the success of transplantation procedures and could have a high predictive value of brain death in comatose patients with brain injuries without fully diagnostic criteria.     

Neuroprotective effects of bloodletting atJing points combined with mild induced hypothermia in acute severe traumatic brain injury

Bloodletting at Jing points has been used to treat coma in traditional Chinese medicine. Mild induced hypothermia has also been shown to have neuroprotective effects. However, the therapeutic effects of bloodletting at Jing points and mild induced hypothermia alone are limited. Therefore, we investigated whether combined treatment might have clinical effectiveness for the treatment of acute severe traumatic brain injury. Using a rat model of traumatic brain injury, combined treatment substantially alleviated cerebral edema and bloodbrain barrier dysfunction. Furthermore, neurological function was ameliorated, and cellular necrosis and the inflammatory response were lessened. These findings suggest that the combined effects of bloodletting at Jing points(20 μL, twice a day, for 2 days) and mild induced hypothermia(6 hours) are better than their individual effects alone. Their combined application may have marked neuroprotective effects in the clinical treatment of acute severe traumatic brain injury.     

Fast-tracking regenerative medicine for traumatic brain injury

Traumatic brain injury remains a global health crisis that spans all demographics,yet there exist limited treatment options that may effectively curtail its lingering symptoms.Traumatic brain injury pathology entails a progression from primary injury to inflammation-mediated secondary cell death.Sequestering this inflammation as a means of ameliorating the greater symptomology of traumatic brain injury has emerged as an attractive treatment prospect.In this review,we recapitulate and evaluate the important developments relating to regulating traumatic brain injury-induced neuroinflammation,edema,and blood-brain barrier disintegration through pharmacotherapy and stem cell transplants.Although these studies of stand-alone treatments have yielded some positive results,more therapeutic outcomes have been documented from the promising area of combined drug and stem cell therapy.Harnessing the facilitatory properties of certain pharmaceuticals with the anti-inflammatory and regenerative effects of stem cell transplants creates a synergistic effect greater than the sum of its parts.The burgeoning evidence in favor of combined drug and stem cell therapies warrants more elaborate preclinical studies on this topic in order to pave the way for later clinical trials.     

Management of a DBS System in Patients With Traumatic Brain Injury: Case Report

Introduction: The use of deep brain stimulation (DBS) is growing. While these patients may suffer from traumatic brain injuries, treatment guidelines for these patients have not yet been reported. This case report demonstrates a strategy for traumatic brain injury after DBS implantation. Clinical presentation: A 46‐year‐old man underwent bilateral DBS in the posterior subthalamic area for essential tremor, which improved both distal and proximal tremor. Two years later, he underwent emergent hematoma evacuation due to a motor vehicle associated injury. A 23‐year‐old male patient presented with severe Tourette's syndrome characterized by a vocal and self lip biting motor tic. There was a good effect of chronic bilateral thalamic DBS at CM‐Pf. Five months later, he had acute subdural hematoma after a motorcycle accident. Instead of removing stimulation electrodes immediately after traumatic brain injury, the patient was reassessed after recovery. Merged preoperative magnetic resonance images and brain computed tomography images, and clinical reassessments were used to plan future treatment. Conclusion: We recommend removing only the hematoma, leaving the electrodes in position, and then reassessing the electrode position using merged images. The clinical correlation with electrode migration also should be checked. If the patient can tolerate stimulation with a minor displacement, the electrodes should be left in position and the stimulation parameter needs to be adjusted. If not, the stimulation electrodes should be deactivated or repositioned appropriately, depending on the patient's conditions.     

长期昏迷的促醒治疗

脑外伤所致的长期昏迷的治疗是一个医学难题，本文就近年长期昏迷的促醒治疗作一综述。     

金尔伦治疗急性重型脑外伤的临床研究

目的　探讨金尔伦治疗急性重型颅脑损伤患者的疗效和安全性。方法　 13 1名急性重型颅脑伤病人随机分成金尔伦治疗组 (n =62 )和对照组 (n =69) ,观察治疗早期病人GCS评分变化和远期疗效。结果　金尔伦组患者GCS评分在用药后第 5d开始明显优于对照组 (P <0 0 5 ) ;金尔伦组病死率 2 4 2 % ,对照组病死率 5 0 7% ,两组相比有显著性差异 (P <0 0 1)。结论　金尔伦可以降低急性重型颅脑外伤病人颅内压的升高幅度 ,缩短昏迷时间 ,降低伤残率 ,促进病人神经功能恢复 ,改善预后。     

经皮电刺激干预对液压脑损伤大鼠中脑组织microRNA表达的调控作用

目的 检测经皮电刺激对创伤昏迷大鼠脑神经组织中microRNA变化的调控作用。方法雄性SD大鼠12只,随机分为假手术对照组、创伤昏迷组和电刺激组,每组各4只。对创伤昏迷组与电刺激组大鼠进行中等力度液压脑损伤,伤后30rain对电刺激组大鼠行右前肢经皮电刺激,伤后1h取各动物中脑组织,经RNA抽提检测后,利用表达谱芯片进行检测,扫描杂交结果并对荧光强度进行标准化后行统计分析。结果创伤昏迷组大鼠中脑节段脑组织中,33种microRNA表达上调,38种microRNA表达下降。经皮电刺激组大鼠中脑组织中7种microRNA表达升高,48种microRNA表达降低。结论创伤昏迷动物中脑组织中出现明显的microRNA变化。经皮电刺激对创伤昏迷动物中脑组织中microRNA表达具有明确的调控作用,表明电刺激干预对中脑传导束及核团可能存在调节作用。     

Utilizing pharmacotherapy and mesenchymal stem cell therapy to reduce inflammation following traumatic brain injury

The pathologic process of chronic phase traumatic brain injury is associated with spreading inflammation,cell death,and neural dysfunction.It is thought that sequestration of inflammatory mediators can facilitate recovery and promote an environment that fosters cellular regeneration.Studies have targeted post-traumatic brain injury inflammation with the use of pharmacotherapy and cell therapy.These therapeutic options are aimed at reducing the edematous and neurodegenerative inflammation that have been associated with compromising the integrity of the blood-brain barrier.Although studies have yielded positive results from anti-inflammatory pharmacotherapy and cell therapy individually,emerging research has begun to target inflammation using combination therapy.The joint use of anti-inflammatory drugs alongside stem cell transplantation may provide better clinical outcomes for traumatic brain injury patients.Despite the promising results in this field of research,it is important to note that most of the studies mentioned in this review have completed their studies using animal models.Translation of this research into a clinical setting will require additional laboratory experiments and larger preclinical trials.     

Selective CDK inhibitors： promising candidates for future clinical traumatic brain injury trials

Traumatic brain injury induces secondary injury that contributes to neuroinflammation, neuronal loss, and neurological dysfunction. One important injury mechanism is cell cycle activation which causes neuronal apoptosis and glial activation. The neuroprotective effects of both non-selective （Flavopiridol） and selective （Roscovitine and CR-8） cyclin-dependent kinase inhibitors have been shown across mukiple experimental traumatic brain injury models and species. Cyclin-depen- dent kinaseinhibitors, administered as a single systemic dose up to 24 hours after traumatic brain injury, provide strong neuroprotection-reducing neuronal cell death, neuroinflammation and neurological dysfunction. Given their effectiveness and long therapeutic window, cyclin-dependent kinase inhibitors appear to be promising candidates for clinical traumatic brain injury trials.     

Mechanisms responsible for the effect of median nerve electrical stimulation on traumatic brain injury-induced coma：orexin-A-mediated N-methyl-D-aspartate receptor subunit NR1 upregulation

Electrical stimulation of the median nerve is a noninvasive technique that facilitates awakening from coma. In rats with traumatic brain inju-ry-induced coma, median nerve stimulation markedly enhances prefrontal cortex expression of orexin-A and its receptor, orexin receptor 1. To further understand the mechanism underlying wakefulness mediated by electrical stimulation of the median nerve, we evaluated its effects on the expression of the N-methyl-D-aspartate receptor subunit NR1 in the prefrontal cortex in rat models of traumatic brain injury-in-duced coma, using immunohistochemistry and western blot assays. In rats with traumatic brain injury, NR1 expression increased with time after injury. Rats that underwent electrical stimulation of the median nerve (30 Hz, 0.5 ms, 1.0 mA for 15 minutes) showed elevated NR1 expression and greater recovery of consciousness than those without stimulation. These effects were reduced by intracerebroventric-ular injection of the orexin receptor 1 antagonist SB334867. Our results indicate that electrical stimulation of the median nerve promotes recovery from traumatic brain injury-induced coma by increasing prefrontal cortex NR1 expressionvia an orexin-A-mediated pathway.     

重型颅脑损伤大骨瓣开颅减压术后的远期疗效分析

目的探讨标准外伤大骨瓣开颅术治疗重型颅脑损伤的远期效果。方法回顾性分析167例采用标准外伤大骨瓣开颅术治疗的重型颅脑损伤病人（大骨瓣组）的远期疗效，与采用常规开颅术治疗的42例病人（对照组）进行对比。结果大骨瓣组随访期内死亡21例，发生长期昏迷31例，慢性脑积水142例，脑穿通畸形43例，硬膜下积液145例，迟发性癫痫58例，颅脑损伤后综合征55例。对照组死亡10例，发生长期昏迷4例．慢性脑积水20例，脑穿通畸形7例，硬膜下积液30例，迟发性癫痫15例，颅脑损伤后综合征18例。大骨瓣组病死率低于对照组（P〈0．05），长期昏迷、慢性脑积水、脑穿通畸形和颅脑损伤后综合征发生率高于对照组（P〈0.05）。结论采用大骨瓣开颅减压术治疗重型颅脑损伤，远期病死率较低：早期昏迷发生率虽有所增加．但复苏率明显高于对照组；慢性脑积水、脑穿通畸形发生率增加．但通过采取积极治疗，如早期颅骨成形、脑脊液分流术等可获得较好的疗效，因而远期生活质量较对照组好．     

Electrical treatment of reduced consciousness: experience with coma and Alzheimer's disease

The right median nerve can be stimulated electrically to help arouse the central nervous system for persons with reduced levels of consciousness. The mechanisms of central action include increased cerebral blood flow and raised levels of dopamine. There is 11 years of experience in the USA of using nerve stimulation for acute coma after traumatic brain injury. There is a much longer period of experience by neurosurgeons in Japan with implanted electrodes on the cervical spinal cord for persons in the persistent vegetative state (PVS). But the use of right median nerve electrical stimulation (RMNS) for patients in the subacute and chronic phases of coma is relatively new. Surface electrical stimulation to treat anoxic brain injury as well as traumatic brain injury is evolving. Novel applications of electrical stimulation in Amsterdam have produced cognitive behavioural effects in persons with early and mid-stage Alzheimer's disease employing transcutaneous electrical nerve stimulation (TENS). Improvements in short-term memory and speech fluency have also been noted. Regardless of the aetiology of the coma or reduced level of awareness, electrical stimulation may serve as a catalyst to enhance central nervous system functions. It remains for the standard treatments and modalities to retrain the injured brain emerging from reduced levels of consciousness.     

重型颅脑损伤术后发生脑积水的危险因素分析

目的探讨重型颅脑损伤患者术后脑积水发生的危险因素。方法回顾性分析手术后276例重型颅脑损伤手术患者的临床资料。随访6个月后根据脑积水诊断标准,分为脑积水组(47例)和非脑积水组(229例),采用单因素分析和逐步Logistic回归分析,比较两组患者颅内脑挫裂伤、脑室出血、硬膜下血肿、硬膜外血肿、颅骨损伤、颅骨线型骨折、脑脊液蛋白水平及压力等因素。结果随访结果显示,重型颅脑损伤患者术后脑积水发生率为17.03%(47/276);单因素分析结果显示脑积水组和非脑积水组在年龄、脑室出血、硬膜下血肿、昏迷(有无、持续时间)、格拉斯哥昏迷评分(Glasgow Coma Scale,GCS)、去骨瓣减压术、创伤性蛛网膜下腔出血(traumatic subarachnoid hemorrhage,tSAH)、加尔维斯顿定位和失忆测试(Galveston Orientation and Amnesia Test,PTA)、功能独立性测评(Function Independent Measure,FIM)的差异均有统计学意义(P0.05);Logistic回归结果显示高龄、硬膜下血肿、昏迷时间长、GCS低分值,去骨瓣减压术与重型颅脑创伤后的脑积水的发生显著正相关。结论高龄、有硬膜下血肿、GCS评分低、接受去骨瓣减压术是重型颅脑创伤后脑积水的危险因素。     

经颅多普勒超声在重型颅脑创伤救治中的临床应用

重型颅脑创伤（sTBI）的临床监测手段多以体格检查、影像学检查为主,而这些手段无法迅速有效地诊断、监测sTBI病理生理过程。经颅多普勒超声（TCD）可以无创、实时地测量大脑大动脉的血流状态,获得脑血流动力学信息,通过分析脑血流速度及方向、血管自身调节功能、远端血管阻力变化来监测脑血管狭窄、痉挛程度并评估颅内压、识别脑死亡。本文围绕TCD在sTBI救治中的临床应用综述如下。     

Neuroprotection and traumatic brain injury: theoretical option or realistic proposition

PURPOSE OF REVIEW: Preclinical studies have shown that treatment to limit secondary cell damage can significantly improve outcome after traumatic brain injury. In contrast, neuroprotection trials in human traumatic brain injury have failed to convincingly demonstrate therapeutic benefit. Recent literature has begun to address this discrepancy between preclinical and clinical trials. RECENT FINDINGS: Perhaps the most important recent observations relate to the potential role of apoptosis in secondary brain injury. Because apoptosis peaks more than 24 h after injury, concepts about the therapeutic window for traumatic brain injury treatment have changed. Apoptosis and necrosis are in delicate balance and inhibition of one cell death pathway may enhance the other. This raises questions about the ultimate effectiveness of treatment strategies directed toward a single injury mechanism. In contrast to clinical head injury, which reflects a complex multi-factorial disorder, animal models are generally designed to address only a single injury component and are performed in genetically inbred animals of a single sex. Moreover, animal studies usually employ pretreatment or early posttreatment administration, examine moderate rather than severe injury, fail to examine brain drug levels or treatment optimization, and do not use an intent-to-treat methodology. SUMMARY: Recognition of these methodological differences between animal and human studies has led to new trial design proposals. For clinical studies, there should be better stratification of patients, a focus on moderate injury and earlier treatment, and larger sample sizes. Animal experiments should better parallel clinical studies and address therapeutic window and treatment optimization. Recognition of multiple cell death pathways should lead to new treatment strategies--including both combination drug treatment and drugs that affect multiple components of the secondary injury cascade.     

Plasma fibronectin is neuroprotective following traumatic brain injury

Promotion of repair and regeneration following traumatic brain injury remains a challenging clinical problem. While significant efforts have been made to reduce inhibitory extracellular matrix expression following central nervous system injury, much less attention has been given to the role of endogenous reparative matrix proteins, such as fibronectin. Traumatic brain injury leads to increased levels of plasma-derived fibronectin in the brain tissue, though the specific function of this protein following neurotrauma was unknown. In this study, we utilized conditional plasma fibronectin (pFN) knockout mice to examine the role of fibronectin following a traumatic insult. Injured mice deficient in pFN performed significantly worse on both motor and cognitive tasks, had significantly increased lesion volume and apoptotic cell death, and had significantly less phagocytic cells in the injured cortex compared to injured mice with normal pFN levels. Moreover, intravenous injections of fibronectin prior to the injury restored the neural deficits seen in the pFN deficient mice to that of wild type injured mice. These results demonstrate that fibronectin is neuroprotective to the traumatically injured brain and identify a novel target for therapeutic interventions.     

Glutethimide treatment of disabling action tremor in patients with multiple sclerosis and traumatic brain injury

Glutethimide has been used to control essential tremor. Its efficacy in the treatment of disabling cerebellar and rubral tremor was assessed in an open study of six patients with multiple sclerosis and two patients with traumatic brain injury. Functional and quantitative tremor severity was assessed before treatment and 7 to 14 days after a stable dose was achieved. Six of eight patients exhibited visible functional benefit from treatment with glutethimide; abstract testing results correlated well with functional status in most cases. Four patients chose to continue to receive medication. Controlled trials of glutethimide to compare its efficacy with that of other medications used in the treatment of action tremor are indicated.     

Changes in white matter late after severe traumatic brain injury in childhood

Severe traumatic brain injury in childhood, particularly that complicated by raised intracranial pressure, has significant long-term effects on the brain. Since magnetic resonance imaging provides a means of visualizing neuroanatomic structure in exquisite detail, the scope of this review is to revisit the pathology of traumatic brain injury described in recent clinical imaging studies. Acute imaging provides insight into the acute mechanism of focal and diffuse injury. There is some reduction in threshold for white matter pathology in the hemisphere ipsilateral to injury. After injury, there may be long-term effects on white matter architecture and the potential for brain growth. In this context, the pattern of hippocampal rather than parahippocampal gyrus tissue loss provides insight into the likely cause of white matter injury being cerebral hypoperfusion.     

Injury of the dentatorubrothalamic tract in patients with post-traumatic tremor following mild traumatic brain injury: a case-control study

Post-traumatic movement disorder is one of the sequelae of traumatic brain injury. The dentatorubrothalamic tract(DRTT) is reported to be involved in the control of movement. Therefore, injury of the DRTT can be accompanied by abnormal movements, including ataxia, tremor, or dystonia. We investigated DRTT injuries in 27 patients who showed post-traumatic tremor in at least one of four extremities following mild traumatic brain injury. We classified DRTT injuries based on diffusion tensor tractography parameters and configuration: type A: the DRTT showed narrowing, type B: the DRTT showed partial tearing, and type C: the DRTT showed discontinuation. Fractional anisotropy and fiber number of the DRTT were significantly decreased in patients compared with the healthy controls. Based on our DRTT injury classification, among the 54 hemispheres of the 27 patients, type A injury occurred in 22 hemispheres(40.7%) of 17 patients, type B injury was present in 15 hemispheres(27.7%) of 10 patients, and type C injury was observed in 8 hemispheres(14.8%) of 6 patients. Our results suggest that diffusion tensor tractography-based evaluation of the DRTT would be useful when determining cause of post-traumatic tremor in patients with mild traumatic brain injury. The study protocol was approved by the Institutional Review Board of Yeungnam University Hospital(YUMC-2018-09-007) on September 5, 2018.