Inflammation and the Silent Sequelae of Stroke

Depression and fatigue are common after stroke and negatively impact the quality of life of stroke survivors. The biological bases of these symptoms are unknown, but an abundance of data point to a role for inflammation. This review highlights evidence supporting the contribution of inflammation to poststroke depression and poststroke fatigue. Potential treatments for poststroke depression and poststroke fatigue are explored, with a special emphasis on those that modulate the immune response.     

Inflammation in Acute Ischemic Stroke and its Relevance to Stroke Critical Care

Thrombolysis heralded a new era of acute intervention for ischemic stroke, accompanied by an increasing need for comprehensive acute critical care support. There remains the prospect of novel cerebral protection strategies. Cerebral ischemia initiates a complex cascade of events at genomic, molecular, and cellular levels, and inflammation is important in this cascade, both in the CNS and in the periphery. Closely linked events are induction of a classic acute phase protein response, activation of the hypothalamic-pituitary-adrenal axis (HPAA) and sympathetic nervous system (SNS), and rise in body temperature, all of which appear to importantly influence the outcome. Thrombolysis aside, various therapeutic strategies have been trialed without success recently, primarily directed at influencing neuronal activity and survival directly. Inflammation itself offers an attractive target, mainly because of its potential to exacerbate the spread of damage to the ischemic penumbra. A promising novel therapeutic approach is the interleukin-1 receptor antagonist (IL-1ra), which limits the action of the cytokine IL-1, a pivotal mediator in the pathophysiology of acute neurodegeneration. Critical care has much to offer some patients after acute ischemic stroke, including the delivery of acute interventions, often with very short therapeutic time windows, physiological support, and the management of complications. We discuss inflammation and its mediators in acute ischemic stroke, the systemic stress, and acute phase protein responses to acute ischemic stroke, how inflammation is relevant in deteriorating ischemic stroke, the impact of physiological variables, and both current and emerging interventions for acute ischemic stroke.     

Psychopathy and Human Evil: An Overview

The term “psychopath” usually conjures images of serial killers or acts of genocide. Less frequently considered are those who are intelligent enough to avoid detection by the criminal justice system while hiding in the boardrooms of corporations or lurking in the halls of government institutions. This article provides an overview of psychopathy and human evil by exploring the personality characteristics, organization, and cognitive style of the psychopath, the role of superego pathology, contributions from the field of attachment, and ways in which dissociation plays a role in psychopathy and the potential for confusing this with the dissociative structuring of the mind. The article closes with a brief discussion about “corporate” or “successful psychopaths” and how they have a negative impact on culture and society.     

Epilepsy and Persian Culture: An Overview

This article reviews the manner in which Persian culture viewed the problem of epilepsy. Beginning with the Avesta, the earliest Persian text on health and sickness, the medical literature on treatments of epilepsy common in Iran are reviewed. The article also explores popular Persian concepts that try to explain the causes of the morbus sacer.     

Transcranial Magnetic Stimulation as an Investigative Tool for Motor Dysfunction and Recovery in Stroke: An Overview for Neurorehabilitation Clinicians

Rationale: An improved understanding of motor dysfunction and recovery after stroke has important clinical implications that may lead to the design of more effective rehabilitation strategies for patients with hemiparesis. Scope: Transcranial magnetic stimulation (TMS) is a safe and painless tool that has been used in conjunction with other existing diagnostic tools to investigate motor pathophysiology in stroke patients. Since TMS emerged more than two decades ago, its application in clinical and basic neuroscience has expanded worldwide. TMS can quantify the corticomotor excitability properties of clinically affected and unaffected muscles and can probe local cortical networks as well as remote but functionally related areas. This provides novel insight into the physiology of neural circuits underlying motor dysfunction and brain reorganization during the motor recovery process. This important tool needs to be used with caution by clinical investigators, its limitations need to be understood, and the results should to be interpreted along with clinical evaluation in this patient population. Summary: In this review, we provide an overview of the rationale, implementation, and limitations of TMS to study stroke motor physiology. This knowledge may be useful to guide future rehabilitation treatments by assessing and promoting functional plasticity.     

Genetics of Epilepsy: An Overview

Studies of the genetics of epilepsy have, until recently, involved epidemiologic or segregation analyses of phenotypic characteristics of a number of seizure disorders. Technical advances in molecular biology involving gene mapping and gene identification have made it possible to examine the heritability of various epilepsy syndromes. Using “reverse genetics” or positional cloning, it is possible to identify an abnormal protein through gene isolation and cloning. Genes are localized through analysis of linkage to phenotypic markers (proteins) or DNA markers such as restriction fragment length polymorphisms, variable number of tandem repeats, and dinucleotides. Methods used to obtain DNA of interest involve digestion of genomic DNA with specific restriction endonucleases or amplification of DNA by polymerase chain reaction technology. Gel electrophoresis is the basis for the separation of different sized DNA. Inherited disorders for which a gene has been cloned or localized have highly penetrant, well-defined clinical phenotypes with no remissions and abundant clinical material. Genetic epilepsies, however, are variably penetrant age-dependent disorders with heterogenous clinical phenotypes. Despite these difficulties, three genetic epilepsies have been mapped to specific chromosomes: benign familial neonatal convulsions to 20q, juvenile myoclonic epilepsy to 6p, and Baltic progressive myoclonus epilepsy to 21q. Further progress in understanding genetic epilepsies will depend on better definition of syndrome phenotypes, isolation of the epilepsy gene(s), and identification of the abnormal protein(s).     

Inflammation and coagulation. An overview

Inflammation and coagulation are two main host-defence systems that interact with each other. Inflammation activates coagulation and coagulation modulates the inflammatory activity in many ways. The contributing molecular pathways are reviewed. Thrombin and activated protein C (APC) and its receptor EPCR constitute a major physiological regulatory system to control vascular wall permeability during sepsis. Pro-inflammatory cellular effects of coagulation proteases as well as the anti-inflammatory effects of APC/EPCR are mediated by signaling via protease activated receptors PAR on mononuclear cells, endothelial cells, platelets, fibroblast, and smooth muscle cells. The beneficial effects of APC in sepsis are mainly dependent on the PAR-mediated cell-protective properties rather than the anticoagulant protease function on coagulation cofactors FV/Va and FVIII/VIIIa. Animal experiments with signaling selective APC-variants show promise in improving the therapeutic efficacy and safety of APC in sepsis.     

Obesity in Bipolar Disorder: An Overview

Bipolar disorder (BD) is associated with obesity, overweight, and abdominal obesity, and BD individuals with obesity have a greater illness burden. Factors related to BD, its treatment, and the individual may all contribute to BD??s association with obesity. Management strategies for the obese BD patient include use of medications with better metabolic profiles, lifestyle interventions, and adjunctive pharmacotherapy for weight loss. Obesity-related psychiatric and medical comorbidities should also be assessed and managed. Bariatric surgery may be an option for carefully selected patients. Greater research into the theoretical underpinnings and clinical management of the BD-obesity connection is needed.     

Emergency Management of Seizures: An Overview

Summary: The drugs currently used in the emergency management of seizures are chiefly phenytoin, phenobarbital, diazepam, lorazepam, and paraldehyde. The combination of intravenous phenytoin and lorazepam has the advantages of rapid onset of action, sustained efficacy, and freedom from drug interactions. The intermittent oral or rectal administration of diazepam is especially useful for acute home treatment of recurrent seizures. Phenytoin prodrug (ACC-9653), an investigational new drug, is promptly absorbed after intramuscular injection. Unlike phenytoin, it does not require propylene glycol and high alkalinity for solubility and therefore does not produce soft-tissue injury after parenteral administration. It appears to be close to an ideal drug for the emergency management of seizures.     

Sport Psychiatry in Childhood and Adolescence: An Overview

This review explores the importance and relevance of sport during childhood and adolescence, utilizing traditional stage theories of development. The literature supports the notion that sport is a necessary study as a health issue and a preventative tool in the field of psychiatry. Play and sport in childhood and adolescence enhance development physically, mentally, and socially. Participating in athletics encourages the development of leadership skills, self-esteem, muscle development and overall physical health. There is a lack of literature in the important area of sport psychiatry especially when considering beneficial, not deficit oriented youth athletic development. Child psychiatrists need to begin researching sport in order to develop a comprehensive understanding of how athletics can enhance the mental and physical health of youth.     

Free Will,Self-Governance and Neuroscience: An Overview

Given dramatic increases in recent decades in the pace of scientific discovery and understanding of the functional organization of the brain, it is increasingly clear that engagement with the neuroscientific literature and research is central to making progress on philosophical questions regarding the nature and scope of human freedom and responsibility. While patterns of brain activity cannot provide the whole story, developing a deeper and more precise understanding of how brain activity is related to human choice and conduct is crucial to the development of realistic, just, and intellectually rigorous models of human agency and moral responsibility. In this special issue, we acknowledge that “free will” and “moral responsibility” are not concepts with which neuroscience can directly engage, and instead focus on self-governance, and the capacities that contribute to self-governance, which are more tractable for scientific investigation and are prerequisites for the presence of moral responsibility.     

Stroke Mimics: An Important Source of Bias in Acute Ischemic Stroke Research

Study Objective: Stroke mimics may be difficult distinguish from acute ischemic strokes and are often treated with alteplase though not by intent. We report the characteristics, frequency, and outcomes of stroke mimics treated at our institution. Using our data, we then explore how the inclusion of stroke mimics in stroke outcomes research may be an important source of bias. Methods: We retrospectively identified all patients treated with alteplase in our emergency department from August 2013 to December 2017 for suspected acute ischemic stroke. We collected the following variables: gender, age, risk factors (hypertension, diabetes, and atrial fibrillation), admission glucose, admission National Institute of Health Stroke Scale, admission mean arterial pressure, onset-to-treatment time, adverse events, discharge diagnosis, length of stay, discharge NIHSS, discharge destination, and 3 month modified Rankin score. Results: One hundred and eighteen patients were treated with alteplase for suspected acute ischemic stroke of which 33 (27.9%) were stroke mimics. Compared to ischemic strokes, stroke mimics were younger (median age 53 versus 69; P < .0003); were less likely to have vascular risk factors (hypertension [51.5% versus 78.8%; P < .005] diabetes (9.1% versus 32.9%; P < .007), and atrial fibrillation (3.0% versus 23.5%; P < .006). The most common stroke mimic was transient ischemic attack (33.3%). Stroke mimics were significantly more likely to be discharged home (75.8% versus 41.2%; P < .002). Outcomes unadjusted for stroke mimics led to artificial inflation of a favorable discharge destination. Conclusions: Inclusion of stroke mimics led to an artificial inflation of a favorable discharge destination for our entire cohort. Our study highlights the potential for bias in reporting favorable outcomes if appropriate adjustment accounting for stroke mimics does not occur.