Intervention for executive functions after traumatic brain injury: a systematic review, meta-analysis and clinical recommendations

A systematic review of studies that focused on the executive functions of problem solving, planning, organising and multitasking by adults with traumatic brain injury (TBI) was performed through 2004. Qualitative and quantitative methods were used to evaluate the 15 studies that met inclusion criteria. Demographic variables, design and intervention features, and impairment and activity/participation outcomes (ICF) (World Health Organization, 2001) were documented. Five randomised control treatment (RCT) studies used step-by-step, metacognitive strategy instruction (MSI) and outcomes were evaluated in a meta-analysis. Effect sizes (ESs) from immediate impairment outcomes after MSI and "control" intervention were similar to each other, and both were significantly larger than chance. ESs from immediate activity/participation outcomes after MSI were significantly larger than the ESs from control intervention, and both were significantly larger than chance. These results, along with positive outcomes from the other group, single-subject design and single case studies, provided sufficient evidence to make the clinical recommendation that MSI should be used with young to middle-aged adults with TBI, when improvement in everyday, functional problems is the goal (Level A) (American Academy of Neurology, 2004). Although maintenance effects were generally positive, there was insufficient data quantitatively to evaluate this. Furthermore, there was insufficient evidence to make clinical recommendations for children or older adults. Intervention that trained verbal reasoning and multi-tasking was promising, although the evidence is insufficient to make clinical recommendations at this time. Additional research needs were highlighted.     

Intracranial pressure monitors in traumatic brain injury: a systematic review

We conducted a systematic review to examine the relationship between intracranial pressure monitors (ICP) monitors and mortality in traumatic brain injury (TBI). We systematically searched for articles that met the following criteria: (1) adults patients, (2) TBI, (3) use of an ICP monitor, (4) point estimate for mortality with ICP monitoring (5) adjustment for potential confounders. Six observational studies were identified with 11,371 patients. There was marked between-study heterogeneity that precluded a pooled analysis. Patients with ICP monitors had different clinical characteristics and received more ICP targeted therapy in the ICU. Four studies found no significant relationship between ICP monitoring and survival, while the other two studies demonstrated conflicting results. Significant confounding by indication in observational studies limits the examination of isolated TBI interventions. More research should focus on interventions that affect TBI careplan systems. Further research is needed to identify which subset of severe TBI patients may benefit from ICP monitoring.     

血清S-100B对轻型颅脑损伤诊断价值的系统评价和Meta分析

目的系统评价血清学标志物S-100B对于轻型颅脑损伤（mTBI）患者颅内损伤的诊断价值。 方法计算机检索PubMed、EMbase、The Cochrane Library、中国知网、中国生物医学数据库、维普、万方数据库,筛选S-100B预测mTBI后颅内损伤的诊断性试验,检索时限为自建库至2022年5月27日。由2名研究员根据纳入和排除标准筛选文献、数据提取,并采用QUADAS-2工具评价纳入研究的偏倚风险,采用Meta-DiSc 1.4软件分析血清S-100B对mTBI的诊断价值。 结果共纳入21篇文献,包括8057例患者。Meta分析结果显示：S-100B诊断mTBI颅内损伤的诊断比值比为5.55（95%CI：3.47~8.87）,合并灵敏度为0.91（95%CI：0.88~0.93）,合并特异度为0.29（95%CI：0.28~0.30）,合并阳性似然比为1.35（95%CI：1.25~1.47）、合并阴性似然比为0.26（95%CI：0.16~0.44）。S-100B诊断mTBI颅内损伤的综合受试者工作特征曲线的曲线下面积为0.760。 结论S-100B对于mTBI患者颅内损伤有一定的诊断价值,可作为筛查工具辅助急诊医生进行筛查。     

The effect of pediatric traumatic brain injury on behavioral outcomes: a systematic review

Aim To review systematically the empirical evidence on traumatic brain injury (TBI) during childhood and subsequent behavioral problems. Method An initial literature search with keywords ‘brain injury,’‘children,’ and ‘behavior’ was conducted using Web of Knowledge and PubMed databases. Ancestry was also used. Original research studies published between 1990 and February 2012 focusing on behavioral outcomes of children sustaining TBI from ages 0 to 18 years were included. Results Fifty studies, varying considerably in methodologies, were included in the review. Findings showed that up to 50% of brain‐injured children are at risk for presenting with specific behavioral problems and disorders. These problems may emerge shortly or several years after injury and often persist and even worsen with time. These behavioral impairments appear to be moderated by the family environment. Interpretation Survivors of childhood TBI are at risk for developing and sustaining behavioral impairments. Stronger research is needed to identify cognitive and environmental factors that contribute to the onset and maintenance of these problems. Healthcare providers should ensure adequate follow‐up and assessment of a child’s behavioral, social, and neurocognitive domains. Caregivers should be encouraged to provide positive environments and parenting styles, which may help reduce chronic behavioral problems after brain injury.     

Statin on post-stroke epilepsy: A systematic review and meta-analysis

IntroductionRecent research has shown that statins can reduce the incidence of epilepsy after stroke, especially ischemic stroke, but the results are inconsistent. In view of current stroke guidelines do not recommend the use of anti-epileptic drugs (AED) for the prevention of epilepsy after stroke, statins may be a good choice. The purpose of this study was to conduct a systematic review and meta-analysis to determine the effect of statins on the prevention of epilepsy after stroke.MethodsCorrelative cohort studies were identified through search of PubMed, Cochrane Library and Embase databases. The main outcomes included post-stroke epilepsy (PSE) and early-onset seizure (ES). Subgroup analyses and Sensitivity analysis were performed to evaluate the influences of the predefined study characteristics on the outcome.ResultsSeven studies were included (n = 40831). Statin use was associated with a lower risk of PSE (including 6 articles) (odds ratio [OR] 0.60, 95% confidence interval [CI] [0.42, 0.84], p = 0.003), and there is a remarkable effect in ES (including 6 articles) (OR 0.36, 95% CI [0.25, 0.54], p < 0.00001).ConclusionAppropriate use of statins after stroke can reduce the risk of PSE, especially ES.     

Prevalence of tic disorders: a systematic review and meta-analysis

This study evaluated the prevalence of tic disorders. MEDLINE and EMBASE databases were searched, using terms specific to Tourette syndrome and tic disorders, for studies of incidence, prevalence, and epidemiology. Thirty-five studies reporting data from 1985-2011 on the incidence or prevalence of tic disorders in a defined population were included. One reported incidence, and 34 reported prevalence. Meta-analysis of 13 studies of children yielded a prevalence of Tourette syndrome at 0.77% (95% confidence interval, 0.39-1.51%). Prevalence is higher in boys: 1.06% of boys were affected (95% confidence interval, 0.54-2.09%) vs 0.25% of girls (95% confidence interval, 0.05-1.20%). Transient tic disorder comprised the most common tic disorder in children, affecting 2.99% (95% confidence interval, 1.60-5.61%). Meta-analysis of two studies assessing adults for Tourette syndrome revealed a prevalence of 0.05% (95% confidence interval, 0.03-0.08%). The prevalence of tic disorders was higher in all studies performed in special education populations. Tic disorders are more common in children than adults, in boys than girls, and in special education populations. Parents, educators, healthcare professionals, and administrators should be aware of the frequency with which tic disorders occur, and ensure proper access to appropriate care.     

Insomnia following traumatic brain injury: a review

Sleep disturbances after a traumatic brain injury (TBI) have received very little scientific attention despite the fact that several studies indicate that they may occur in 30% to 70% of patients. For individuals with TBI, problems falling asleep or maintaining sleep can exacerbate other symptoms such as pain, cognitive deficits, fatigue, or irritability. Sleep disturbances can thus compromise the rehabilitation process and the ability to return to work. This article reviews the evidence on the epidemiology, etiology, and treatment of insomnia in the context of TBI and proposes areas for future research. Prevalence estimates of insomnia complaints in TBI patients are summarized. Potential etiological factors (i.e., lesions to the nervous system, anxiety) and possible consequences of insomnia (i.e., fatigue, cognitive problems) in the context of TBI are discussed. Finally, pharmacological and psychological treatments previously shown effective to treat insomnia in healthy individuals are discussed as valuable treatment options for TBI patients. Increased knowledge about the high prevalence, diagnosis, and potential etiological factors of insomnia following TBI may promote a better identification, evaluation, and treatment of sleeping difficulties in this population.     

Psychiatric disorders and traumatic brain injury

Psychiatric disorders after traumatic brain injury (TBI) are frequent. Researches in this area are important for the patients’ care and they may provide hints for the comprehension of primary psychiatric disorders. Here we approach epidemiology, diagnosis, associated factors and treatment of the main psychiatric disorders after TBI. Finally, the present situation of the knowledge in this field is discussed.     

Melatonin in autism spectrum disorders: a systematic review and meta-analysis

Aim The aim of this study was to investigate melatonin‐related findings in autism spectrum disorders (ASD), including autistic disorder, Asperger syndrome, Rett syndrome, and pervasive developmental disorders, not otherwise specified. Method Comprehensive searches were conducted in the PubMed, Google Scholar, CINAHL, EMBASE, Scopus, and ERIC databases from their inception to October 2010. Two reviewers independently assessed 35 studies that met the inclusion criteria. Of these, meta‐analysis was performed on five randomized double‐blind, placebo‐controlled studies, and the quality of these trials was assessed using the Downs and Black checklist. Results Nine studies measured melatonin or melatonin metabolites in ASD and all reported at least one abnormality, including an abnormal melatonin circadian rhythm in four studies, below average physiological levels of melatonin and/or melatonin derivates in seven studies, and a positive correlation between these levels and autistic behaviors in four studies. Five studies reported gene abnormalities that could contribute to decreased melatonin production or adversely affect melatonin receptor function in a small percentage of children with ASD. Six studies reported improved daytime behavior with melatonin use. Eighteen studies on melatonin treatment in ASD were identified; these studies reported improvements in sleep duration, sleep onset latency, and night‐time awakenings. Five of these studies were randomized double‐blind, placebo‐controlled crossover studies; two of the studies contained blended samples of children with ASD and other developmental disorders, but only data for children with ASD were used in the meta‐analysis. The meta‐analysis found significant improvements with large effect sizes in sleep duration (73min compared with baseline, Hedge’s g 1.97 [95% confidence interval {CI} CI 1.10–2.84], Glass’s Δ 1.54 [95% CI 0.64–2.44]; 44min compared with placebo, Hedge’s g 1.07 [95% CI 0.49–1.65], Glass’s Δ 0.93 [95% CI 0.33–1.53]) and sleep onset latency (66min compared with baseline, Hedge’s g−2.42 [95% CI −1.67 to −3.17], Glass’s Δ−2.18 [95% CI −1.58 to −2.76]; 39min compared with placebo, Hedge’s g−2.46 [95% CI −1.96 to −2.98], Glass’s Δ−1.28 [95% CI −0.67 to −1.89]) but not in night‐time awakenings. The effect size varied significantly across studies but funnel plots did not indicate publication bias. The reported side effects of melatonin were minimal to none. Some studies were affected by limitations, including small sample sizes and variability in the protocols that measured changes in sleep parameters. Interpretation Melatonin administration in ASD is associated with improved sleep parameters, better daytime behavior, and minimal side effects. Additional studies of melatonin would be helpful to confirm and expand on these findings.     

Substance use among persons with traumatic brain injury: a review

This paper provides a review of the current literature in the area of substance use and traumatic brain injury (TBI). Collectively, these studies demonstrate that substance use and SUD are common in the TBI population both pre- and post-injury, are a frequent causative factor in injury acquisition, complicate the rehabilitation process, and have substantial negative impact on individual health and well being. Further, individuals with a demonstrated SUD and concurrent TBI are likely to be severely limited in their ability to access SUD care due to physical barriers. This literature is reviewed and then considered in terms of its general weaknesses. Finally, a brief outline of future research needs is provided.     

Mood disorders following traumatic brain injury

Mood disorders are a frequent complication of traumatic brain injury that exerts a deleterious effect on the recovery process and psychosocial outcome of brain injured patients. Prior psychiatric history and impaired social support have been consistently reported as risk factors for developing mood disorders after traumatic brain injury (TBI). In addition, biological factors such as the involvement of the prefrontal cortex and probably other limbic and paralimbic structures may play a significant role in the complex pathophysiology of these disorders. Preliminary studies have suggested that selective serotonin reuptake inhibitors such as sertraline, mood stabilizers such as sodium valproate, as well as stimulants and ECT may be useful in treating these disorders. Mood disorders occurring after TBI are clearly an area of neuropsychiatry in which further research in etiology as well as treatment is needed.     

Mood disorders following traumatic brain injury

Mood disorders are a frequent complication of traumatic brain injury that exerts a deleterious effect on the recovery process and psychosocial outcome of brain injured patients. Prior psychiatric history and impaired social support have been consistently reported as risk factors for developing mood disorders after traumatic brain injury (TBI). In addition, biological factors such as the involvement of the prefrontal cortex and probably other limbic and paralimbic structures may play a significant role in the complex pathophysiology of these disorders. Preliminary studies have suggested that selective serotonin reuptake inhibitors such as sertraline, mood stabilizers such as sodium valproate, as well as stimulants and ECT may be useful in treating these disorders. Mood disorders occurring after TBI are clearly an area of neuropsychiatry in which further research in etiology as well as treatment is needed.     

Neuroendocrine disorders after traumatic brain injury

Traumatic brain injury (TBI) is the most common cause of death and disability in young adults living in industrialised countries, in which 180-250 persons per 100 000 per year die or are hospitalised as a result. Neuroendocrine derangements after TBI have received increasing recognition in recent years because of their potential contribution to morbidity, and possibly mortality, after trauma. Marked changes of the hypothalamo-pituitary axis have been documented in the acute phase of TBI, with as many as 80% of patients showing evidence of gonadotropin deficiency, 18% of growth hormone deficiency, 16% of corticotrophin deficiency and 40% of patients demonstrating vasopressin abnormalities leading to diabetes insipidus or the syndrome of inappropriate anti-diuresis. Longitudinal prospective studies have shown that some of the early abnormalities are transient, whereas new endocrine dysfunctions become apparent in the post-acute phase. There remains a high frequency of hypothalamic-pituitary hormone deficiencies among long-term survivors of TBI, with approximately 25% patients showing one or more pituitary hormone deficiencies. This is a higher frequency than previously thought and suggests that most cases of post-traumatic hypopituitarism (PTHP) remain undiagnosed and untreated. PTHP has been associated with adverse outcome both in the acute and chronic phases after injury. These data underscore the need for the identification and appropriate timely management of hormone deficiencies, in order to optimise patient recovery from head trauma, improve quality of life and avoid the long-term adverse consequences of untreated hypopituitarism.     

Cognitive-behavioural therapy for late-life anxiety disorders: a systematic review and meta-analysis

Objective: To examine and estimate the efficacy of cognitive‐behavioural therapy (CBT) for late‐life anxiety disorders. Method: A systematic review and meta‐analysis of randomized controlled trials comparing CBT with i) a waiting‐list control condition and ii) an active control condition controlling for non‐specific effects in patients aged over 60 years and suffering from an anxiety disorder. The main outcome parameter of individual studies, i.e. effect on anxiety, was pooled using the standardized mean difference (SMD). Results: Seven papers fulfilled the inclusion criteria, including nine randomized controlled comparisons for 297 patients. Anxiety symptoms were significantly more reduced following CBT than after either a waiting‐list control condition [SMD = ?0.44 (95 CI: ?0.84 ?0.04), P = 0.03] or an active control condition [SMD = ?0.51 (95 CI: ?0.81, ?0.21), P<0.001]. Additionally, CBT significantly alleviated accompanying symptoms of worrying and depression. Conclusion: Cognitive‐behavioural therapy is efficacious for the treatment of late‐life anxiety disorders.     

促红细胞生成素治疗急性颅脑损伤疗效的meta分析

目的 系统评价促红细胞生成素（EPO）治疗急性颅脑损伤的有效性和安全性。方法 计算机检索The Cochrane Library、Clinical Trials、Web of Science、PubMed、EMbase、中国生物医学文献数据库、中国知网数据库和万方数据库,检索年限均从建库至2018年5月。搜集EPO治疗急性颅脑损伤的临床随机对照试验,试验组采用EPO治疗,对照组采用安慰剂或空白对照。采用RevMan 5.3软件进行meta分析。结果 纳入7项临床随机对照研究,共计1 101例,试验组564例,对照组537例。meta分析显示:EPO显著降低病死率（RR=0.69;95% CI 0.51~0.94;P=0.02）,不能改善神经功能（RR=1.28;95%CI 0.90~1.81;P=0.17）,不增加深静脉血栓形成发生率（RR=1.00;95% CI=0.74~1.35;P=0.99）。结论 EPO治疗急性颅脑损伤可以降低死亡率,无明显严重的不良反应,但不能改善神经功能。     

Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis

A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (≈ 0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD.