Postoperative delirium

Delirium is a global impairment of upper brain functions caused by an organic substrate. It is frequently observed in the postoperative period, particularly in elderly people. Vascular and orthopedic surgery and long-duration surgery are associated with a higher incidence of postoperative delirium. When it occurs, postoperative delirium makes patient management much more difficult, increases costs, and, above all, causes severe discomfort to the patient. Delirium is also associated with higher postoperative mortality and morbidity, and with delayed functional recovery, but it is still unclear whether worse prognosis is directly caused by delirium or results from the neurological damage of which delirium is simply a symptom. Drug therapy should be part of a complex approach to prevent and treat this complication. Neuroleptics like haloperidol and droperidol, and benzodiazepines are usually employed in order to control symptoms like agitation, restlessness, and altered perceptions. Atypical neuroleptics, like risperidone, have not yet been studied in postoperative delirium, although some case reports in which they were successfully used have been published. Physiostigmine is effective in delirium caused by anticholinergic syndrome; vitamins may be useful in alcoholics; melatonin use has been suggested in order to prevent and treat delirium by normalizing sleep-wake cycle alterations. Environmental interventions are often costless and may be very useful to prevent and treat postoperative delirium in patients at risk.     

Delirium in critically ill patients: epidemiology, pathophysiology, diagnosis and management

Delirium is commonly observed in critically ill patients and is associated with negative outcomes. The pathophysiology of delirium is not completely understood. However, alterations to neurotransmitters, especially acetylcholine and dopamine, inflammatory pathways and an aberrant stress response are proposed mechanisms leading to intensive care unit (ICU) delirium. Detection of delirium using a validated delirium assessment tool makes early treatment possible, which may improve prognosis. Patients at high risk of delirium, especially those with cognitive decline and advanced age, should be identified in the first 24 hours of admission to the ICU. Whether these high-risk patients benefit from haloperidol prophylaxis deserves further study. The effectiveness of a multicomponent, non-pharmacological approach is shown in non-ICU patients, which provides proof of concept for use in the ICU. The few studies on this approach in ICU patients suggest that the burden of ICU delirium may be reduced by early mobility, increased daylight exposure and the use of earplugs. In addition, the combined use of sedation, ventilation, delirium and physical therapy protocols can reduce the frequency and severity of adverse outcomes and should become part of routine practice in the ICU, as should avoidance of deliriogenic medication such as anticholinergic drugs and benzodiazepines. Once delirium develops, symptomatic treatment with antipsychotics is recommended, with haloperidol being the drug of first choice. However, there is limited evidence on the safety and effectiveness of antipsychotics in ICU delirium.     

Drug-induced cognitive impairment in the elderly.

Elderly people are more likely than younger patients to develop cognitive impairment as a result of taking medications. This reflects age- and disease-associated changes in brain neurochemistry and drug handling. Delirium (acute confusional state) is the cognitive disturbance most clearly associated with drug toxicity, but dementia has also been reported. The aetiology of cognitive impairment is commonly multifactorial, and it may be difficult to firmly establish a causal role for an individual medication. In studies of elderly hospital patients, drugs have been reported as the cause of delirium in 11 to 30% of cases. Medication toxicity occurs in 2 to 12% of patients presenting with suspected dementia. In some cases CNS toxicity occurs in a dose-dependent manner, often as a result of interference with neurotransmitter function. Drug-induced delirium can also occur as an idiosyncratic complication. Finally, delirium may occur secondary to iatrogenic complications of drug use. Almost any drug can cause delirium, especially in a vulnerable patient. Impaired cholinergic neurotransmission has been implicated in the pathogenesis of delirium and of Alzheimer's disease. Anticholinergic medications are important causes of acute and chronic confusional states. Nevertheless, polypharmacy with anticholinergic compounds is common, especially in nursing home residents. Recent studies have suggested that the total burden of anticholinergic drugs may determine development of delirium rather than any single agent. Also, anticholinergic effects have been identified in many drugs other than those classically thought of as having major anticholinergic effects. Psychoactive drugs are important causes of delirium. Narcotic agents are among the most important causes of delirium in postoperative patients. Long-acting benzodiazepines are the commonest drugs to cause or exacerbate dementia. Delirium was a major complication of treatment with tricyclic antidepressants but seems less common with newer agents. Anticonvulsants can cause delirium and dementia. Drug-induced confusion with nonpsychoactive drugs is often idiosyncratic in nature, and the diagnosis is easily missed unless clinicians maintain a high index of suspicion. Histamine H2 receptor antagonists, cardiac medications such as digoxin and beta-blockers, corticosteroids, non-steroidal anti-inflammatory agents and antibiotics can all cause acute, and, less commonly, chronic confusion. Drug-induced confusion can be prevented by avoiding polypharmacy and adhering to the saying 'start low and go slow'. Special care is needed when prescribing for people with cognitive impairment. Early diagnosis of drug-induced confusion, and withdrawal of the offending agent or agents is essential.     

Delirium assessed by Memorial Delirium Assessment Scale in advanced cancer patients admitted to an acute palliative/supportive care unit

Background: Delirium is often unrecognized in cancer patients. The aim of this study was to investigate the prevalence of delirium assessed by the Memorial Delirium Assessment Scale (MDAS) and possible associated factors on admission to an acute palliative/supportive care unit (APSCU). The secondary outcome was to assess changes in MDAS and symptom burden at time of discharge.

Methods: A consecutive sample of advanced cancer patients who were admitted to an APSCU was prospectively assessed for a period of 10 months. Patient demographics, including age, gender, primary diagnosis, Karnofsky status, stage of disease, and educational level were collected. The Edmonton Symptom Assessment Scale (ESAS) and the MDAS were measured at hospital admission and discharge.

Results: A total of 314 patients were surveyed. Of 292 patients with MDAS available at T0, 74 (25.3%) and 24 (8.2%) had a MDAS of 7–12 and ≥13, respectively. At discharge, there was a significant decrease in the number of patients with a MDAS ≥7/30. Higher values of MDAS were associated with age (p?=?.028), a lower Karnofsky status (p?p?=?.04), low level of education (p?=?.002), less awareness of disease (p?p?p?=?.026), hospital stay (p?=?.038) and death (p?p?Conclusion: Delirium is highly prevalent in patients admitted to APSCU, characterized by a low mortality due to early referral. Comprehensive assessment and treatment may allow a decrease in the level of cognitive disorders and symptom burden.     

Early to Long-Term Alterations of CNS Barriers After Traumatic Brain Injury: Considerations for Drug Development

Traumatic brain injury (TBI) is one of the leading causes of death and disability, particularly amongst the young and the elderly. The functions of the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) are strongly impaired after TBI, thus affecting brain homeostasis. Following the primary mechanical injury that characterizes TBI, a secondary injury develops over time, including events such as edema formation, oxidative stress, neuroinflammation, and alterations in paracelullar and transcellular transport. To date, most therapeutic interventions for TBI have aimed at direct neuroprotection during the acute phase and have not been successful. Targeting the barriers of the central nervous system (CNS) could be a wider therapeutic approach, given that restoration of brain homeostasis would benefit all brain cells, including neurons. Importantly, BBB disregulation has been observed even years after TBI, concomitantly with neurological and psychosocial sequelae; however, treatments targeting the post-acute phase are scarce. Here, we review the mechanisms of primary and secondary injury of CNS barriers, the accumulating evidence showing long-term damage to these structures and some of the therapies that have targeted these mechanisms. Finally, we discuss how the injury characteristics (hemorrhagic vs non-hemorrhagic, involvement of head rotation, gray vs white matter), the sex, and the age of the patient need to be carefully considered to improve clinical trial design and outcome interpretation, and to improve future drug development.     

A型主动脉夹层术后谵妄的发生率和危险因素研究

目的研究A型主动脉夹层术后谵妄的发生率和相关危险因素。方法以A型主动脉夹层术后患者为研究对象,以意识错乱评估方法作为谵妄诊断工具,分析术后谵妄的发生率和危险因素。结果共有84例患者纳入研究,发生术后谵妄28例,发生率为33.3%。21例(75%)为一过性谵妄(<24 h);7例(25%)为持续性谵妄。Logistic多因素回归分析结果表明,脑梗死、深低温停循环时间、重症监护病房时间是术后谵妄的危险因素。结论既往脑梗死、深低温停循环时间、重症监护病房持续时间是术后谵妄的独立危险因素。     

Non-Steroidal Anti-Inflammatory Drugs and Cognitive Function: Are Prostaglandins at the Heart of Cognitive Impairment in Dementia and Delirium ?

Studies of non-steroidal anti-inflammatory drugs (NSAIDs) in rheumatoid arthritis imply that inflammation is important in the development of Alzheimer’s disease (AD). However, these drugs have not alleviated the symptoms of AD in those who have already developed dementia. This suggests that the primary mediator targeted by these drugs, PGE2, is not actively suppressing memory function in AD. Amyloid-β oligomers appear to be important for the mild cognitive changes seen in AD transgenic mice, yet amyloid immunotherapy has also proven unsuccessful in clinical trials. Collectively, these findings indicate that NSAIDs may target a prodromal process in mice that has already passed in those diagnosed with AD, and that synaptic and neuronal loss are key determinants of cognitive dysfunction in AD. While the role of inflammation has not yet become clear, inflammatory processes definitely have a negative impact on cognitive function during episodes of delirium during dementia. Delirium is an acute and profound impairment of cognitive function frequently occurring in aged and demented patients exposed to systemic inflammatory insults, which is now recognised to contribute to long-term cognitive decline. Recent work in animal models is beginning to shed light on the interactions between systemic inflammation and CNS pathology in these acute exacerbations of dementia. This review will assess the role of prostaglandin synthesis in the memory impairments observed in dementia and delirium and will examine the relative contribution of amyloid, synaptic and neuronal loss. We will also discuss how understanding the role of inflammatory mediators in delirious episodes will have major implications for ameliorating the rate of decline in the demented population.     

醒脑静对中重度颅脑损伤患者血清sFractalkine含量的影响及临床意义

目的探讨醒脑静对创伤性中重度颅脑损伤患者血清炎性细胞因子sFractalkine（sFKN）的影响及其临床意义。方法 82例中重度颅脑损伤患者随机分为醒脑静治疗组（42例）和对照组（40例）,采用双抗体夹心酶联免疫吸附法（ELISA）,检测2组治疗后1、3、7、10 d后血清sFKN含量,并观察2组临床疗效,分析醒脑静对颅脑损伤的治疗作用及机制。结果醒脑静治疗后,颅脑损伤患者各个检测时点（第10天除外）血清sFKN水平均有所下降,尤以治疗后3～7 d血清sFKN水平下降明显（P〈0.05）。醒脑静治疗组1周清醒率高于对照组,高热率低于对照组（P〈0.05）。结论 sFKN作为前炎性因子参与了颅脑损伤的病理生理过程,可以作为创伤后炎症的标志物,为颅脑创伤的治疗提供依据。醒脑静能显著降低创伤性颅脑损伤患者早期血清sFKN水平,从而减轻高热、脑水肿、脑缺氧等创伤引发的并发症,提高昏迷患者1周清醒率。     

Antipsychotics,Delirium, and Acute Respiratory Distress Syndrome: What Is the Link?

Acute respiratory distress syndrome (ARDS) is an acute inflammatory process that impairs the ability of the lungs to oxygenate and ultimately leads to respiratory failure. Patients who develop ARDS often have prolonged and complicated hospital courses putting them at risk for intensive care unit (ICU) delirium. Patients with ICU delirium often need chemical sedation, mechanical ventilation, prolonged duration of ICU and hospital stays, and they experience long‐term cognitive impairment and increased mortality. In a patient with ARDS, ICU delirium further complicates the hospital course and increases the risk of morbidity and mortality. Antipsychotics are prescribed to decrease the severity and duration of ICU delirium, thus potentially decreasing their risk of morbidity and mortality. However, antipsychotics are associated with many adverse effects including respiratory failure. Given the long‐term sequelae associated with the development of ICU delirium and the risks associated with antipsychotic use, clinicians must weigh the risks and benefits of antipsychotic use. This review investigates the interrelationship between ARDS, delirium, and antipsychotic use. In addition to discussing relevant studies evaluating antipsychotics for the prevention and treatment of delirium, we investigate safety concerns with the use of antipsychotics, especially as they relate to ARDS. Using the data compiled in this review, clinicians can make an informed decision about the use of antipsychotics for the prevention or treatment of delirium, with special consideration for their patients with ARDS. Future studies are needed to critically evaluate antipsychotic timing, dose, and duration for the prevention and treatment of ICU delirium and specifically evaluate the impact in special populations, particularly patients with ARDS.     

Glucagon-like peptide-1 receptor agonist Exendin-4 improves neurological outcomes by attenuating TBI- induced inflammatory responses and MAPK activation in rats

Traumatic brain injury (TBI) can be exacerbated and prolonged for months or even years by chronic inflammatory processes with long-term consequences on neurodegeneration and neurological impairment. However, there are no clear pharmacological therapies of benefit to manage neurological dysfunctions, which, relating to the molecular mechanisms underlying the behavioral deficits after TBI, have yet to be fully identified. Recently, a glucagon-like peptide 1 (GLP-1) agonist, Exendin-4, was approved not only for the treatment of type 2 diabetes mellitus, but it also played a neurotrophic role in various CNS neurological diseases. In this study, we evaluated the neuroprotective effects of Exendin-4 on neurological outcome, cerebral blood flow, neurodegeneration, and inflammatory responses by utilizing a cortical contusion impact injury (CCI) model in rats. We found that TBI rats displayed neurological impairments, neurodegeneration, reduction of cerebral blood flow, and inflammatory responses, while Exendin-4 promoted neurological, cognitive, and cerebral blood flow recovery and attenuated neural degeneration and inflammatory cytokines after TBI. Furthermore, Exendin-4 treatment significantly diminished the TBI-induced overexpression of TNFα and IL-1β, as well as phosphorylation of p38 and ERK1/2. These data suggest a strong beneficial action of the glucagon-like peptide-1 receptor agonist Exendin-4 in improving neurological outcomes by attenuating inflammatory responses induced by traumatic brain injury, which is of therapeutic potential for TBI.     

Cognitive deficits in delirium: assessment over time.

Delirium is commonly defined as a transient organic brain syndrome characterized by concurrent disorders of attention, perception, thinking, memory, psychomotor behavior, and the sleep-wake cycle. One of the difficulties in studying delirium is that symptoms tend to fluctuate over the course of the day. Pre-existing organic brain disease appears to be a significant risk factor for the development of delirium, and numerous studies have shown a high rate of delirium in patients with cerebrovascular disease, Parkinson's disease, and Alzheimer's disease. The cognitive deficits associated with delirium have not been widely studied in a systematic, quantitative fashion. Following resolution of the frank delirium, documented cognitive deficits can be observed, and may persist in a diluted form for a period of months. Residual cognitive deficits may be due to a minimal and persistent confusion or to an underlying brain disorder.     

综合医院老年患者谵妄的临床特点及诊治

谵妄是意识障碍的一种,临床以意识、定向力、记忆力、思维、感知和行为发生紊乱为特征,急性起病,呈波动性病程。可见于各种躯体疾病,尤其是老年人。临床上识别谵妄并不容易,常被误诊为痴呆或其他精神科疾病,目前有很多量表帮助非精神科专业人员识别谵妄,从而及早请精神科医师会诊,利于早期诊断和早期治疗。尚没有被批准用于谵妄的治疗药物,但是临床实践中结合药物治疗、病因治疗及环境支持治疗,能够在一定程度上缓解谵妄,降低死亡率。     

Emerging treatments for traumatic brain injury

Background: This review summarizes promising approaches for the treatment of traumatic brain injury (TBI) that are in either preclinical or clinical trials. Objective: The pathophysiology underlying neurological deficits after TBI is described. An overview of select therapies for TBI with neuroprotective and neurorestorative effects is presented. Methods: A literature review of preclinical TBI studies and clinical TBI trials related to neuroprotective and neurorestorative therapeutic approaches is provided. Results/conclusion: Nearly all Phase II/III clinical trials in neuroprotection have failed to show any consistent improvement in outcome for TBI patients. The next decade will witness an increasing number of clinical trials that seek to translate preclinical research discoveries to the clinic. Promising drug- or cell-based therapeutic approaches include erythropoietin and its carbamylated form, statins, bone marrow stromal cells, stem cells singularly or in combination or with biomaterials to reduce brain injury via neuroprotection and promote brain remodeling via angiogenesis, neurogenesis, and synaptogenesis with a final goal to improve functional outcome of TBI patients. In addition, enriched environment and voluntary physical exercise show promise in promoting functional outcome after TBI, and should be evaluated alone or in combination with other treatments as therapeutic approaches for TBI.     

创伤性脑损伤相关神经炎症的研究进展 #br#

创伤性脑损伤（TBI）发生时,外力立即造成神经系统损害。这种原发性损伤触发了体内生化级联以及新 陈代谢和细胞变化在内的继发性神经损害,称为继发性脑损伤。TBI后的神经炎症是持续的神经元损伤的关键因 素。神经炎症涉及损伤后细胞和分子调控机制,包括神经胶质（小胶质细胞和星形胶质细胞）的激活,引起脑内的炎 症介质的释放,导致周围免疫细胞的募集。了解 TBI炎症病理生理学的最新进展对于制定更有效的治疗策略至关 重要。     

Cooling the injured brain: how does moderate hypothermia influence the pathophysiology of traumatic brain injury

Neither any neuroprotective drug has been shown to be beneficial in improving the outcome of severe traumatic brain injury (TBI) nor has any prophylactically-induced moderate hypothermia shown any beneficial effect on outcome in severe TBI, despite the optimism generated by preclinical studies. This contrasts with the paradox that hypothermia still is the most powerful neuroprotective method in experimental models because of its ability to influence the multiple biochemical cascades that are set in motion after TBI. The aim of this short review is to highlight the most recent developments concerning the pathophysiology of severe TBI, to review new data on thermoregulation and induced hypothermia, the regulation of core and brain temperature in mammals and the multiplicity of effects of hypothermia in the pathophysiology of TBI. Many experimental studies in the last decade have again confirmed that moderate hypothermia confers protection against ischemic and non-ischemic brain hypoxia, traumatic brain injury, anoxic injury following resuscitation after cardiac arrest and other neurological insults. Many posttraumatic adverse events that occur in the injured brain at a cellular and molecular level are highly temperature-sensitive and are thus a good target for induced hypothermia. The basic mechanisms through which hypothermia protects the brain are clearly multifactorial and include at least the following: reduction in brain metabolic rate, effects on cerebral blood flow, reduction of the critical threshold for oxygen delivery, blockade of excitotoxic mechanisms, calcium antagonism, preservation of protein synthesis, reduction of brain thermopooling, a decrease in edema formation, modulation of the inflammatory response, neuroprotection of the white matter and modulation of apoptotic cell death. The new developments discussed in this review indicate that, by targeting many of the abnormal neurochemical cascades initiated after TBI, induced hypothermia may modulate neurotoxicity and, consequently, may play a unique role in opening up new therapeutic avenues for treating severe TBI and improving its devastating effects. Furthermore, greater understanding of the pathophysiology of TBI, new data from both basic and clinical research, the good clinical results obtained in randomized clinical trials in cardiac arrest and better and more reliable cooling methods have given hypothermia a second chance in treating TBI patients. A critical evaluation of hypothermia is therefore mandatory to elucidate the reasons for previous failures and to design further multicenter randomized clinical trials that would definitively confirm or refute the potential of this therapeutic modality in the management of severe traumatic brain injuries.     

Adenosine Neuromodulation and Traumatic Brain Injury

Adenosine is a ubiquitous signaling molecule, with widespread activity across all organ systems. There is evidence that adenosine regulation is a significant factor in traumatic brain injury (TBI) onset, recovery, and outcome, and a growing body of experimental work examining the therapeutic potential of adenosine neuromodulation in the treatment of TBI. In the central nervous system (CNS), adenosine (dys)regulation has been demonstrated following TBI, and correlated to several TBI pathologies, including impaired cerebral hemodynamics, anaerobic metabolism, and inflammation. In addition to acute pathologies, adenosine function has been implicated in TBI comorbidities, such as cognitive deficits, psychiatric function, and post-traumatic epilepsy. This review presents studies in TBI as well as adenosine-related mechanisms in co-morbidities of and unfavorable outcomes resulting from TBI. While the exact role of the adenosine system following TBI remains unclear, there is increasing evidence that a thorough understanding of adenosine signaling will be critical to the development of diagnostic and therapeutic tools for the treatment of TBI.Key Words: Adenosine deaminase, adenosine kinase, nucleotidase, nucleoside transport, caffeine, comorbidity.     

Neutrophils and stroke – Can neutrophils mitigate disease in the central nervous system?

Neutrophils are first responders to injury in inflammatory diseases of the central nervous system (CNS) such as ischemic stroke, trauma and intracerebral hemorrhage. Studies carried out in the last three decades showed that neutrophils have mixed effects in animal models of stroke. Some studies correlated the presence of neutrophils to injury. When neutrophil infiltration was reduced by targeting CD18 or intercellular adhesion molecule-1 (ICAM-1) this generated improved outcomes. However other studies showed that when neutrophil infiltration was stimulated prior to stroke, this reduced the burden of disease. Clinical trials did not show a benefit in stroke patients from neutrophil blockade. Neutrophils may be subject to a threshold effect. When they reach a critical ratio relative to the volume of injury in the CNS, they adopt an anti-inflammatory phenotype that is able to reduce disease. When neutrophil infiltration was stimulated by injecting a stroke site in the rat with the chemokine CXCL1, this resulted in reductions in vascular permeability. Similar reductions in permeability were modeled in tissue culture models, in which neutrophils were applied to monolayers of brain endothelial cells. Neutrophils blocked the permeability increases associated with oxygen-glucose deprivation in human brain endothelial monolayers. The evidence suggests that neutrophils might adopt a pro-inflammatory N1 phenotype or an anti-inflammatory N2 phenotype in the CNS depending on environmental cues. The N2 phenotype may be adopted when neutrophil numbers exceed a critical threshold. This suggests that strategies that promote neutrophil infiltration into stroke, and other CNS inflammatory diseases, could result in improved outcomes.     

The evaluation and management of the acutely agitated elderly patient

Delirium is an organic mental syndrome defined by a global disturbance in consciousness and cognition, which develops abruptly and often fluctuates over the course of the day. It is precipitated by medical illness, substance intoxication/withdrawal or medication effect. Delirium is associated with significant morbidity and mortality, and is a leading presenting symptom of illness in the elderly. Elderly patients with altered mental status, including agitation, should be presumed to have delirium until proven otherwise. The clinical manifestations of delirium are highly variable. A mental status evaluation is crucial in the diagnosis of delirium. Medical evaluation and stabilization should occur in parallel. Life-threatening etiologies including hypoxia, hypoglycemia and hypotension require immediate intervention. The differential diagnosis of etiologies of delirium is extensive. Patients with delirium need thorough evaluations to determine the underlying causes of the delirium. Pharmacological agents should be considered when agitated patient has the potential to harm themselves or others, or is impeding medical evaluation and management. Unfortunately, the evidence to guide pharmacologic management of acute agitation in the elderly is limited. Current pharmacologic options include the typical and atypical antipsychotic agents and the benzodiazepines. These therapeutic options are reviewed in detail.     

Effect of anticholinergic burden on treatment modification,delirium and mortality in newly diagnosed dementia patients starting a cholinesterase inhibitor: A population‐based study

Few studies have evaluated the association between anticholinergic burden and treatment modification after starting a cholinesterase inhibitor in clinical practice. We aimed to evaluate the effect of anticholinergic burden on anti‐dementia treatment modification, delirium and mortality. We retrospectively analysed older adults (n = 25 825) who started a cholinesterase inhibitor during 2003–2011 from Korean National Health Insurance Service Senior Cohort Database. High anticholinergic burden was defined as an average daily Anticholinergic Cognitive Burden (ACB) score of >3 during the first 3 months. We investigated the impact of high anticholinergic burden on the rate of treatment modification, delirium and mortality in comparison with minimal ACB (ACB score ≤1) in propensity‐matched cohorts (N = 7438). Approximately 6.0% of patients with dementia were exposed to a high anticholinergic burden within the first three months of treatment. In high anticholinergic burden cohorts, significantly more patients experienced treatment modification (34.9% vs. 32.1%) or delirium (5.6% vs. 3.6%) and the mortality rate was also higher (16.8% vs. 14.1%) than controls. A multivariate Cox proportional hazard regression analysis showed that an average ACB score >3 within the first three months significantly increased the risk of treatment modification (hazard ratio (HR): 1.12, 95% confidence interval (CI): 1.02‐1.24), delirium (HR: 1.52, CI: 1.17‐1.96) and mortality (HR: 1.23, CI: 1.06‐1.41). This study showed that high anticholinergic burden negatively affected the treatment response to cholinesterase inhibitors and that an average ACB score >3 was an independent prognostic factor for delirium or mortality in dementia patients.     

Neural injury following stroke: are Toll-like receptors the link between the immune system and the CNS?

The CNS can exhibit features of inflammation in response to injury, infection or disease, whereby resident cells generate inflammatory mediators, including cytokines, prostaglandins, free radicals and complement, chemokines and adhesion molecules that recruit immune cells, and activate glia and microglia. Cerebral ischaemia triggers acute inflammation, which exacerbates primary brain damage. The regulation of inflammation after stroke is multifaceted and comprises vascular effects, distinct cellular responses, apoptosis and chemotaxis. There are many cell types that are affected including neurons, astrocytes, microglia and endothelial cells, all responding to the resultant neuroinflammation in different ways. Over the past 20 years, researchers examining brain tissue at various time intervals after stroke observed the presence of inflammatory cells, neutrophils and monocytes at the site of injury, as well as the activation of endogenous glia and microglia. This review examines the involvement of these cells in the progression of neural injury and proposes that the Toll-like receptors (TLRs) are likely to be an integral component in the communication between the CNS and the periphery. This receptor system is the archetypal pathogen sensing receptor system and its presence and signalling in the brain following neural injury suggests a more diverse role. We propose that the TLR system presents excellent pharmacological targets for the design of a new generation of therapeutic agents to modulate the inflammation that accompanies neural injury.