Hypopituitarism following traumatic brain injury (TBI): a guideline decalogue

In order to gain further insight into hypopituitarism, that ensues moderate to severe traumatic brain injury (TBI), a group of experts actively working in the field gathered to exchange recent data and concepts. The objective arising from the meeting was to enhance the awareness of both medical specialists and health care administrators on the problem, whose prevalence is higher than previously thought. Guidelines for the diagnosis and management of TBI-mediated hypopituitarism were produced.     

Evolving hypopituitarism as a consequence of traumatic brain injury (TBI) in childhood - call for attention

Hypopituitarism is a common complication of TBI in long-term survivors, more frequent than previously realized. It may be partial or complete, sometimes very subtle without visible lesions in hypothalamo-pituitary region and is diagnosed only by biochemical means. Neuroendocrine abnormalities caused by TBI may have significant implications for the recovery and rehabilitation of these patients. The subjects at risk are those who have suffered moderate to severe trauma, although mild intensity trauma may precede hypopituitarism also. Particular attention should be paid to this problem in children and adolescents. We describe a patient with hypopituitarism thought to be idiopathic due to mild head trauma which caused diabetes insipidus in childhood, gradual failure of pituitary hormones during the period of growth and development, and metabolic (dyslipidemia), physical (obesity), and cognitive impairments in the adult period.     

Anterior pituitary dysfunction following traumatic brain injury (TBI)

Traumatic brain injury (TBI) is the commonest cause of death and disability in young adults living in industrialized countries. Several recent studies have convincingly shown that anterior hypopituitarism is a common complication of head trauma with a prevalence of at least 25% among long-term survivors. This is a much higher frequency than previously thought and suggests that most cases of post-traumatic hypopituitarism (PTHP) remain undiagnosed and untreated. These findings raise important questions about the potential contribution of PTHP to the high physical and neuropsychiatric morbidity seen in this group of patients. In this review, we examine the published reports on the neuroendocrine abnormalities in TBI patients and highlight new data that give novel insights into the natural history of this disorder. We discuss the potential contribution of PTHP to recovery and rehabilitation after injury and the need for the identification and the appropriate and timely management of hormone deficiencies to optimize patient recovery from head trauma, improve quality of life and avoid the long-term adverse consequences of untreated hypopituitarism.     

Metabolic alterations in patients who develop traumatic brain injury (TBI)-induced hypopituitarism

ObjectiveHypopituitarism is associated with metabolic alterations but in TBI-induced hypopituitarism data are scanty. The aim of our study was to evaluate the prevalence of naïve hypertension, dyslipidemia, and altered glucose metabolism in TBI-induced hypopituitarism patients.DesignCross-sectional retrospective study in a tertiary care endocrinology center. 54 adult patients encountering a moderate or severe TBI were evaluated in the chronic phase (at least 12 months after injury) after-trauma. Presence of hypopituitarism, BMI, hypertension, fasting blood glucose and insulin levels, oral glucose tolerance test (if available) and a lipid profile were evaluated.ResultsThe 27.8% of patients showed various degrees of hypopituitarism. In particular, 9.3% had total, 7.4% multiple and 11.1% isolated hypopituitarism. GHD was present in 22.2% of patients. BMI was similar between the two groups. Hypopituitaric patients presented a higher prevalence of dyslipidemia (p < 0.01) and altered glucose metabolism (p < 0.005) with respect to non hypopituitaric patients. In particular, triglycerides (p < 0.05) and HOMA-IR (p < 0.02) were higher in hypopituitaric TBI patients.ConclusionsWe showed that long-lasting TBI patients who develop hypopituitarism frequently present metabolic alterations, in particular altered glucose levels, insulin resistance and hypertriglyceridemia. In view of the risk of premature cardiovascular death in hypopituitaric patients, major attention has to been paid in those who encountered a TBI, because they suffer from the same comorbidities and may present other deterioration factors due to complex pharmacological treatments and restriction in participation in life activities and healthy lifestyle.     

基于颅脑外伤患者认知障碍特点的临床治疗对策

目的基于颅脑外伤患者认知障碍（CI）的临床对策初探。 方法选择吴川市人民医院脑外科及广东医科大学附属廉江医院脑卒中科自2017年1月至2018年1月收治的60例颅脑外伤后CI患者作为研究对象,所有患者接受颅脑外伤综合治疗（常规治疗+高压氧治疗+脑康复治疗）,记录患者各项临床资料（基本资料、类型、诊断）,对患者治疗前后认知功能[洛文斯顿认知功能量表(LOT-CA)]进行评估和分析治疗后认知功能的改善情况。 结果60例颅脑外伤患者的CI表现：9例（15%）为逻辑推理力降低,19例（32%）为记忆功能减退,8例（13%）为注意力不集,8例（13%）为感知感觉力下降,16例（27%）为语言功能下降。双侧半球损伤、右侧半球损伤、左侧半球损伤后CI患者经治疗后LOT-CA评分均高于入院时评分,差异有统计学意义（P<0.05）。 结论颅脑外伤综合治疗对不同类型和损伤部位颅脑外伤后CI患者的疗效确切,临床工作中应重视并积极治疗颅脑外伤后患者的认知功能,以改善患者的预后。     

Effect of computerized cognitive rehabilitation in comparison between young and old age after traumatic brain injury

Introduction:Cognitive dysfunction reduces patients’ quality of life and social participation with traumatic brain injury (TBI). Computerized cognitive rehabilitation is increasingly being used for cognitive therapy in TBI patients. The purpose of this study was to investigate the influence of age on the effect of computerized cognitive rehabilitation in cognitive dysfunction after TBI.Material and methods:A total of 34 patients with cognitive dysfunction after TBI were enrolled. Participants performed 30 sessions of computerized cognitive rehabilitation (Comcog) for 6 weeks. A cognitive evaluation was performed before and after treatment with Mini-Mental State Examination (MMSE) and Computerized Neurophyschologic Test (CNT).Results:There were no cognitive tests that differed between the young group and the old group at baseline. However, after computerized cognitive rehabilitation, the young group showed significant improvement compared to the old group in verbal memory, visual memory, attention, and visuo-motor coordination tests. The young group showed improvement in MMSE, verbal and visual memory, and visuo-motor coordination tests after computerized cognitive rehabilitation. In contrast, the old group showed significant improvement only in MMSE and visual learning test, one of the visual memory tests.Conclusion:Our findings demonstrate that age may be an important factor related to the effect of computer cognitive rehabilitation on cognitive dysfunction after TBI. Methodologically more ordered studies with larger sample sizes are needed in the future.     

血浆蛋白水平变化与颅脑损伤程度的相关性分析

【】目的：探讨颅脑外伤患者的血浆蛋白变化与损伤程度的相关性,为辅助诊断急性颅脑损伤提供参考,减少迟发性脑损伤的发生率。方法：选取我院159例急性颅脑外伤当天直接送入我院就诊的患者。依据Glasgow 评分,分为轻型组53例,中型组53例,重型组53例。同时,选取在我院治疗的癫痫病人53例作为对照组。入院后根据患者的病情给予适当的营养治疗,四组在入院的第2d,7d,14d早上空腹静脉采血,立即送至检验科测定血浆白蛋白、丙氨酸氨基转移酶(ALT),比较各组之间不同时间段血浆蛋白含量。结果：急性颅脑损伤程度越重,血浆白蛋白下降越明显,ALT上升越明显。急性颅脑损伤程度与血浆白蛋白含量呈负相关,与ALT呈正相关。重型组、中型组血浆白蛋白含量显著低于对照组,差异有统计学意义(P<0.05)。轻型组与对照组相比,未见明显差异;重型组、中型组血浆ALT含量比对照组显著升高,差异有统计学意义(P<0.05)。轻型组与对照组相比,未见明显差异。结论：血浆蛋白水平变化与颅脑损伤程度有密切关系。急性颅脑损伤发生后,机体各个器官正常表达的各种蛋白将会异常分泌,使血浆蛋白水平发生变化,血浆白蛋白降低,ALT分泌增加,血浆蛋白水平变化越大,表明患者颅脑损伤程度越重。     

The effect of cranioplasty in cognitive and functional improvement: Experience of post traumatic brain injury inpatient rehabilitation

To investigate the effect of cranioplasty on rehabilitation of post-traumatic brain injury (TBI) patients, 37 patients with TBI were arranged by retrospectively assessment study. Those TBI patients receiving in-hospital rehabilitation in the Department of Rehabilitation in a medical center of South Taiwan from 2010 to 2015 were assigned into two groups: A and B. All patients entered the multidisciplinary holistic in-patient rehabilitation training for about 1 month. Patients in Group A received decompressive craniectomy (DC), patients in Group B received DC and cranioplasty. All assessments were arranged right on admission and before discharge. The functional activity evaluation included muscle power and Barthel index (BI), and cognitive function evaluation, including the Rancho Los Amigo Scale, Mini Mental State Examination (MMSE), Community Mental State Examination (CMSE), and the Luria-Nebraska Neuropsychological Battery-Screening Test Short Form (LNNBS). The results showed that there were synergetic effects of cranioplasty on post-TBI patients with rehabilitation training, especially in the BI score, and cognitive improvement in CMSE and LNNBS.     

Improving motor and cognitive recovery following severe traumatic brain injury using advanced emotional audio-video stimulation: Lessons from a case report

Rationale:It is estimated that about 6 million people suffer from severe traumatic brain injury (TBI) each year (73 cases per 100,000 people). TBI may affect emotional, sensory-motor, cognitive, and psychological functions with a consequent worsening of both patient and his/her caregiver''s quality of life. In recent years, technological innovations allowed the development of new, advanced sensory stimulation systems, such as Neurowave, to further stimulate residual cognitive abilities and, at the same time, evaluate residual cognition.Patient concern:An 69-year-old Italian man entered our neurorehabilitation unit with a diagnosis of minimally conscious state following severe TBI. He breathed spontaneously via tracheostomy and was fed via percutaneous gastrostomy. At the neurological examination, the patient showed severe tetraparesis as he showed fluctuating alertness and responsiveness to external stimuli and opened the eyes without stimulation.Diagnosis:Patient was affected by subarachnoid hemorrhage and frontotemporal bilateral hematoma, which were surgically treated with decompressive craniotomy and subsequent cranioplasty about 6 months before.Interventions:The patient underwent a neuropsychological and clinical evaluation before (T0) and after a conventional rehabilitation cycle (T1), and after a Neurowave emotional stimulation-supported rehabilitative cycle (T2).Outcomes:Following conventional rehabilitation (T1), the patient achieved a partial improvement in behavioral responsiveness; there was also a mild improvement in the caregiver''s distress. Conversely, Neurowave emotional stimulation session determined (at T2) a significant improvement of the patient''s behavioral responsiveness, cognition, and in the caregiver''s distress. The P300 recording in response to the NES showed a significant change of P300 magnitude and latency.Discussion:Our data suggest that emotional-integrated sensory stimulation using adequate visual stimuli represents a beneficial, complementary rehabilitative treatment for patients in minimally conscious state following a severe TBI. This may occur because stimuli with emotional salience can provide a reliable motivational resource to stimulate motor and cognitive recovery following severe TBI.     

Circulating Epstein-Barr virus (EBV) in HIV-infected patients and its relation with primary brain lymphoma.

OBJECTIVE: To analyze Epstein-Barr virus (EBV) load at different HIV infection stages and its relation with brain lymphoma. DESIGN: A cross-sectional study was conducted on 172 HIV-infected individuals: 62 asymptomatic HIV carriers (group A), 30 HIV progressors (group B), 73 AIDS patients (group C), seven AIDS patients with brain lymphoma (group C-BL); and 26 blood donors (group BD) as healthy carriers. EBV load was measured in peripheral blood mononuclear cells (PBMC) and plasma samples using a semi-quantitative PCR method. RESULTS: PBMC-EBV levels in HIV-infected patients were higher than in the blood donors (p<0.05). No differences in PBMC-EBV loads were found in groups A, B, or C (p>0.05), while the C-BL group had significantly lower levels (p<0.05). Similar PBMC-EBV loads were seen in HIV-infected patients with CD4+ T cell counts higher than 50/mm(3) (p>0.05), while significantly lower levels were found in cases with less than 50 cells/mm(3) (p<0.05). In all HIV-infected patients, plasma-EBV load was lower than, or similar to, PBMC-EBV load, unlike 2/7 HIV-positive brain lymphoma patients. CONCLUSIONS: During HIV infection PBMC-EBV load rises in comparison to healthy carriers, but decreases when immunosuppression progresses and CD4+ T cell count becomes <50/mm(3). Circulating EBV is mainly cell-associated in the HIV-infected population. Neither PBMC-EBV nor plasma-EBV loads would be useful to diagnose brain lymphoma in AIDS patients.     

计算机辅助认知训练对脑损伤患者认知功能和抑郁的影响

目的观察计算机辅助的认知训练对脑损伤患者认知功能和抑郁的影响。方法采用单盲方法,选择脑损伤后18d至1年,有认知功能障碍和抑郁症状的患者46例,随机分为计算机辅助训练组（26例）和传统康复训练组（20例）。所有患者均接受传统康复训练（Bobath、Brunnstrom等神经发育促进技术,2次／d,30～40min／次）和药物治疗。同时给予辅助训练组患者计算机辅助认知训练,30min／次,2次／d。训练时间均为5周。认知功能判断采用神经行为认知功能检查量表（NCSE）和画钟试验,并结合临床判定;抑郁状态评定采用汉密尔顿抑郁量表（HAMD,〉8分为抑郁）。结果训练前,辅助训练组与传统康复训练组NCSE量表的定向能力、专注能力、语言能力、记忆能力、计算能力、推理能力、结构组织能力评分,画钟试验评分及HAMD评分,差异均无统计学意义,P〉0．05。①训练后,两组NCSE量表各项评分及画钟试验评分均较训练前提高（P〈0．05或P〈0．01）;与传统康复训练组比较,辅助训练组除结构组织能力外,NCSE其他各项评分及画钟试验评分均提高,差异有统计学意义（P〈0．05或P〈0．01）。②训练后,辅助训练组HAMD评分较训练前显著降低（P〈0．01）,传统康复训练组无明显改变;辅助训练组HAMD评分较传统康复训练组下降（P〈0．05）。结论计算机辅助的认知训练能够改善脑损伤患者认知功能障碍,并使抑郁症状得到改善。     

颅脑创伤后外周血白细胞的动态变化及意义

目的研究颅脑创伤（TBI）后不同时间患者外周血白细胞（WBC）的动态变化规律及其临床意义。方法测定77例TBI患者伤后不同时间点外周血WBC的动态变化,分析WBC变化的影响因素。结果重型组受伤后第1、4、7天的WBC明显高于轻型组;感染组整体变化趋势明显高于无感染组,且第7、14天WBC与无感染组比较均有统计学差异（P均〈0．01）;病情恶化组第1、4、7、14天的WBC均明显高于治疗好转组（P〈0．05或〈0．01）。结论WBC的早期升高与伤情有关;伤后4d内WBC升高不能作为判定是否感染的指标,伤后1—2周仍持续升高者可作为判定感染的指标之一;伤后1周内WBC明显升高者预后较差。反之预后较好。     

认知功能及脑部病灶特征对脑损伤患者急性应激障碍的影响

目的探讨脑损伤患者急性应激障碍(ASD)的现状及认知功能、脑部病灶特征对其的影响。方法采用一般情况调查表、斯坦福急性应激反应问卷(SASRQ)、简易智力状况检查(MMSE)、疼痛视觉模拟评分(VAS)对脑损伤住院的患者517例进行问卷调查。结果 517例ASD患者SASRQ总分(66.44±43.761)分,8～39分369例(71.37%),40～56分51人(9.87%),57～146分97人(18.76%)。认知功能(β=-0.634)、烦扰程度(β=0.174)、疼痛(β=0.085)、年龄(β=-0.101)、丧偶(β=0.057)、大专(β=-0.095)、本科及以上(β=-0.072),经颅多普勒(TCD)结果1根血管异常(β=0.115)、≥3根异常(β=0.089)最终进入回归方程(P0.05)。结论脑损伤患者存在明显的急性应激症状,认知障碍、烦扰程度重、疼痛程度大、低教育水平、TCD结果异常的患者发生ASD的可能性越大。     

Pituitary function in subjects with mild traumatic brain injury: a review of literature and proposal of a screening strategy

Traumatic brain injury (TBI) is an important public health problem all over the world. The level of consciousness of the patients and the severity of the brain injury is commonly evaluated by the Glascow Coma Scale as mild, moderate and severe TBI. When we consider the high frequency of mild TBI (MTBI) among the all TBI patients the burden of the pituitary dysfunction problem in this group could not be ignored. However, one of the most important and still unresolved questions is which patients with MTBI should be screened for hypopituitarism? Another type of head trauma which could be considered as the subgroup of MTBI is sports related chronic repetitive head trauma. Therefore, in this review we will discuss the frequency, characteristics and current management of pituitary dysfunction in patients with MTBI including the subjects exposed to sports related chronic mild head trauma.     

Monitoring of glucose in brain, adipose tissue, and peripheral blood in patients with traumatic brain injury: a microdialysis study

Background:

Episodes of hyperglycemia are considered to be a secondary insult in traumatically brain-injured patients and have been shown to be associated with impaired outcome. Intensive insulin therapy to maintain a strict glucose level has been suggested to decrease morbidity and mortality in critically ill patients but this aggressive insulin treatment has been challenged. One aspect of strict glucose control is the risk of developing hypoglycemia. Extracellular intracerebral hypoglycemia monitored by intracerebral microdialysis has been shown to correlate with poor outcome. Monitoring of blood glucose during neurointensive care is important because adequate glucose supply from the systemic circulation is crucial to maintain the brain''s glucose demand after brain injury. This study investigates the correlation of glucose levels in peripheral blood, subcutaneous (SC) fat, and extracellular intracerebral tissue in patients with severe traumatic brain injury during neurointensive care.

Methods:

In this study, we included 12 patients with severe traumatic brain injury. All patients received one microdialysis catheter each, with a membrane length of 10 mm (CMA 70, CMA Microdialysis AB) in the injured hemisphere of the brain and in the noninjured hemisphere of the brain. An additional microdialysis catheter with a membrane length of 30 mm (CMA 60, CMA Microdialysis AB) was placed in the periumbilical subcutaneous adipose tissue. We studied the correlation among levels of glucose measured in peripheral blood, adipose tissue, and the noninjured hemisphere of the brain during the first 12 hours and during 3 consecutive days in neurointensive care.

Results:

We found a significant positive correlation between levels of glucose in peripheral blood, SC fat, and the noninjured brain during the initial 12 hours but not in injured brain. However, the result varied between the patients during the 3-day measurements. In 7 patients, there was a significant positive correlation between glucose in blood and noninjured brain, while in 4 patients this correlation was poor. In 4 patients, there was a significant positive correlation in injured brain and blood. Furthermore, there was a significant correlation between brain and adipose tissue glucose during the 3-day measurements in 11 out of 12 patients.

Conclusion:

This study indicates that there is a good correlation between blood glucose and adipose tissue during initial and later time points in the neurointensive care unit whereas the correlation between blood and brain seems to be more individualized among patients. This emphasizes the importance of using intracerebral microdialysis to ensure adequate intracerebral levels of glucose in patients suffering from severe traumatic brain injury and to detect hypoglycemia in the brain despite normal levels of blood glucose.