Neuropsychiatric phenotypes of anti-NMDAR encephalitis: a prospective study.

BACKGROUND: Patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis (ANMDARE) show a wide range of behavioral abnormalities and are often mistaken for primary psychiatric presentations. We aimed to determine the behavioral hallmarks of ANMDARE with the use of systematic neuropsychiatric and cognitive assessments. METHODS: A prospective study was conducted, with 160 patients admitted to the National Institute of Neurology and Neurosurgery of Mexico, who fulfilled criteria for possible autoimmune encephalitis and/or red flags along a time window of seven years. Cerebrospinal fluid (CSF) antibodies against the NR1 subunit of the NMDAR were processed with rat brain immunohistochemistry and cell-based assays with NMDA expressing cells. Systematic cognitive, neuropsychiatric, and functional assessments were conducted before knowing NMDAR antibodies results. A multivariate analysis was used to compare patients with and without definite ANMDARE according to antibodies in CSF. RESULTS: After obtaining the CSF antibodies results in 160 consecutive cases, 100 patients were positive and classified as having definite ANMDARE. The most frequent neuropsychiatric patterns were psychosis (81%), delirium (75%), catatonia (69%), anxiety-depression (65%), and mania (27%). Cognition was significantly impaired. A total of 34% of the patients had a predominantly neuropsychiatric presentation without seizures. After multivariate analysis, the clinical hallmarks of ANMDARE consisted of a catatonia-delirium comorbidity, tonic-clonic seizures, and orolingual dyskinesia. CONCLUSIONS: Our study supports the notion of a neurobehavioral phenotype of ANMDARE characterized by a fluctuating course with psychotic and affective symptoms, catatonic signs, and global cognitive dysfunction, often accompanied by seizures and dyskinesia. The catatonia-delirium comorbidity could be a distinctive neurobehavioral phenotype of ANMDARE.

Burnout among healthcare providers in the complex environment of the Middle East: a systematic review.

BACKGROUND: Burnout is a syndrome characterized by emotional exhaustion, increased depersonalization, and a diminished sense of personal accomplishment due to chronic emotional stress at work. Burnout impacts job satisfaction, job performance, vulnerability to illnesses, and interpersonal relationships. There is a gap in the systematic data on the burden of burnout among healthcare professionals from different sectors of healthcare in Middle Eastern countries. Our objective was to examine the burden of burnout among healthcare providers in the Middle East, how it was assessed, which sectors were included, and what interventions have been used. METHODS: Articles were found through a systematic review of search results including PubMed, Web of Science (Thomson Reuters), and PsycINFO (EBSCO) using search terms reflecting burnout in Middle Eastern countries among populations of healthcare providers. Studies were included if they examined a quantitative measure of burnout among healthcare providers in the Middle East. RESULTS: There were 138 articles that met our inclusion criteria for this systematic review. Studies focused on burnout in the Middle East among physicians (N = 54 articles), nurses (N = 55), combined populations of healthcare workers (N = 22), and medical students (N = 7). The Maslach Burnout Inventory was the most common tool to measure burnout. Burnout is common among physicians, nurses, and other healthcare professionals, with prevalence estimates predominantly ranging between 40 and 60%. Burnout among healthcare providers in the Middle East is associated with characteristics of their work environments, exposure to violence and terror, and emotional distress and low social support. CONCLUSIONS: Burnout is highly prevalent among healthcare providers across countries in the Middle East. Previous studies examining burnout in this region have limitations in their methodology. More thoroughly developed epidemiologic studies of burnout are necessary. Health system strengthening is needed in a region that has endured years of ongoing conflict, and there is an urgency to design and implement programs that tackle burnout among health professionals.

Corrigendum to 'Role of electroencephalogram oscillations and the spectrogram in monitoring anaesthesia' [BJA Education 20 (2020) 166-172].

[This corrects the article DOI: 10.1016/j.bjae.2020.01.004.].

Endogenous morphine.

It is now well accepted that endogenous morphine is present in animals, both in invertebrates and vertebrates. It is a key signaling molecule that plays an important role in downregulating physiological responses, such as those in the immune system, including immune elements in the CNS. It has been demonstrated that a specific mu-opiate-receptor subtype, mu3, mediates these downregulatory effects through release of NO. This article examines morphine as an endogenous signaling molecule, in terms of its role in neural and immune regulation.

Cell-surface estrogen receptors mediate calcium-dependent nitric oxide release in human endothelia.

BACKGROUND: Although estrogen replacement therapy has been associated with reduction of cardiovascular events in postmenopausal women, the mechanism for this benefit remains unclear. Because nitric oxide (NO) is considered an important endothelium-derived relaxing factor and may function to protect blood vessels against atherosclerotic development, we investigated the acute effects of physiological levels of estrogen on NO release from human internal thoracic artery endothelia and human arterial endothelia in culture. METHODS AND RESULTS: We tested the hypothesis that estrogen acutely stimulates constitutive NO synthase activity in human endothelial cells by acting on a cell-surface receptor. NO release was measured in real time with an amperometric probe. 17beta-Estradiol exposure to internal thoracic artery endothelia and human arterial endothelia in culture stimulated NO release within seconds in a concentration-dependent manner. 17beta-Estradiol conjugated to bovine serum albumin also stimulated NO release, suggesting action through a cell-surface receptor. Tamoxifen, an estrogen receptor inhibitor, antagonized this action. We further showed with the use of dual emission microfluorometry that 17beta-estradiol-stimulated release of endothelial NO was dependent on the initial stimulation of intracellular calcium transients. CONCLUSIONS: Physiological doses of estrogen immediately stimulate NO release from human endothelial cells through activation of a cell-surface estrogen receptor that is coupled to increases in intracellular calcium.

Opioid and opiate immunoregulatory processes.

The discovery of the ability of the nervous system to communicate through "public" circuits with other systems of the body is attributed to Ernst and Berta Scharrer, who described the neurosecretory process in 1928. Indeed, the immune system has been identified as another important neuroendocrine target tissue. Opioid peptides are involved in this communication (i.e., neuroimmune) and with that of autoimmunoregulation (communication between immunocytes). The significance of opioid neuropeptide involvement with the immune system is ascertained from the presence of novel delta, mu, and kappa receptors on inflammatory cells that result in modulation of cellular activity after activation, as well as the presence of specific enzymatic degradation and regulation processes. In contrast to the relatively uniform antinociceptive action of opiate and opioid signal molecules in neural tissues, the presence of naturally occurring morphine in plasma and a novel mu3, opiate-specific receptor on inflammatory cells adds to the growing knowledge that opioid and opiate signal molecules may have antagonistic actions in select tissues. In examining various disorders (e.g., human immunodeficiency virus, substance abuse, parasitism, and the diffuse inflammatory response associated with surgery) evidence has also been found for the involvement of opiate/opioid signaling in prominent mechanisms. In addition, the presence of similar mechanisms in man and organisms 500 million years divergent in evolution bespeaks the importance of this family of signal molecules. The present review provides an overview of recent advances in the field of opiate and opioid immunoregulatory processes and speculates as to their significance in diverse biological systems.

Estradiol coupling to endothelial nitric oxide stimulates gonadotropin-releasing hormone release from rat median eminence via a membrane receptor.

The median eminence (ME), which is the common termination field for adenohypophysiotropic systems, has been shown to produce nitric oxide (NO), a signaling molecule involved in neuroendocrine secretion. Using an ex vivo technique, 17beta-estradiol exposure to ME fragments, including vascular tissues, stimulated NO release within seconds in a concentration-dependent manner, whereas 17alpha-estradiol or testosterone had no effect. 17Beta-estradiol conjugated to BSA (E2-BSA) also stimulated NO release, suggesting mediation by a membrane surface receptor. Tamoxifen, an estrogen receptor inhibitor, antagonized the action of both 17beta-estradiol and E2-BSA. Furthermore, estradiol-stimulated NO stimulates GnRH release. This was demonstrated by hemoglobin (a NO scavenger), N(omega)-nitro-L-arginine methyl ester, and L-N5-(1-iminoethyl)ornithine (nitric oxide synthase inhibitors) inhibition of estradiol stimulated NO and GnRH release. In this regard, L-N5-(1-iminoethyl)ornithine, specific for endotheliol constitutive nitric oxide synthase, was significantly more potent, suggesting that the estradiol-stimulated NO release arose from vascular endothelial cells. Additionally, the NO-stimulated GnRH release occurs via guanylyl cyclase activation in GnRH nerve terminals, as ODQ, a potent and selective inhibitor of NO-sensitive guanylyl cyclase, abolished the estradiol-stimulated GnRH release. The results suggest that at physiological concentrations, 17beta-estradiol may have immediate actions on ME endothelial cells via nongenomic signaling pathways leading to NO-stimulated GnRH release.

Neuroleptic catatonia and its relationship to psychogenic catatonia.

Neuroleptics are among those pharmacological agents that can cause a nonpsychogenic catatonic state. Neuroleptic malignant syndrome (NMS) is marked by a change in state of consciousness, ranging from withdrawal through stupor to coma. In addition, it is characterized by autonomic dysfunction, hyperthermia, mutism, and rigidity. It is included in the differential diagnosis of the catatonic syndrome. Evidence is reviewed to suggest that agents responsible for improving NMS act on the dopamine (DA) gamma aminobutyric acid (GABA) connections in the mesostriatal and mesolimbic systems and also in the hypothalamus. In addition, based on symptomatology, pathophysiology, and therapeutic mechanisms, the relationship between nonpsychogenic neuroleptic-induced catatonia and psychogenic catatonia is examined.

Psychiatric aspects of patients with malignant ventricular arrhythmias.

The major cause of cardiac mortality in the United States is sudden cardiac death, most often the result of ventricular tachycardia-ventricular fibrillation. Transient risk factors for sudden cardiac death include psychiatric conditions mediated through the CNS. Major advances in the evaluation and treatment of patients who have survived malignant ventricular arrhythmias have been accompanied by challenging management and therapy issues for the psychiatrist involved in the care of such patients. The authors suggest ways to meet these challenges, especially in the care of patients with concomitant anxiety, depression, delirium, or psychosis.

Aprosodia in eight schizophrenic patients.

Research interest in the "negative" symptoms of schizophrenia has increased in recent years. Given the clinical similarity between affective deficits in schizophrenic patients and aprosodic deficits in stroke victims, the authors conducted a study testing for aprosodia in eight schizophrenic patients. Seven were found to have aprosodia with motor components. Further study of the aprosodias may provide some insight into affective disturbance in schizophrenia.

The presence of antibacterial and opioid peptides in human plasma during coronary artery bypass surgery.

Antibacterial peptides, found in both invertebrates and vertebrates, represent a potential innate defense mechanism against microbial infections. However, it is unknown whether this process occurs in humans during surgery. We looked for evidence of release of antibacterial peptides during coronary artery bypass grafting (CABG). We used immunological techniques and antibacterial assays combined with high-performance gel-permeation chromatography, reverse-phase HPLC, N-terminal sequencing and comparison with synthetic standards to characterize the peptide B/enkelytin. We show the presence of anionic antibacterial peptide, the peptide B/enkelytin which correspond to the C-terminal part of proenkephalin A, from the plasma of patients undergoing CABG. Our studies show that peptide B/enkelytin is initially present at low levels in plasma and is then released in increased amounts just after skin incision. Antibacterial assays confirmed that the peptides specifically target gram-positive bacteria. We also demonstrate that peptide B/enkelytin is metabolized in vivo to the opioid peptides methionine-enkephalin-Arg-Phe and methionine-enkephalin, peptides that we show have granulocyte chemotactic activity. These findings suggest that in humans, surgical incision leads to the release of antibacterial peptides. Furthermore, these antibacterial peptides can be metabolized into compounds that have immune-activating properties.

Coexisting central diabetes insipidus and psychogenic polydipsia.

A chronic schizophrenic patient is described in whom central diabetes insipidus and psychogenic polydipsia coexisted. A possible relationship between psychogenic polydipsia and failure of vasopressin release is hypothesized.

Functional brain mapping of the relaxation response and meditation.

Meditation is a conscious mental process that induces a set of integrated physiologic changes termed the relaxation response. Functional magnetic resonance imaging (fMRI) was used to identify and characterize the brain regions that are active during a simple form of meditation. Significant (p<10(-7)) signal increases were observed in the group-averaged data in the dorsolateral prefrontal and parietal cortices, hippocampus/parahippocampus, temporal lobe, pregenual anterior cingulate cortex, striatum, and pre- and post-central gyri during meditation. Global fMRI signal decreases were also noted, although these were probably secondary to cardiorespiratory changes that often accompany meditation. The results indicate that the practice of meditation activates neural structures involved in attention and control of the autonomic nervous system.

Psychotic disorder caused by a general medical condition, with delusions. Secondary "organic" delusional syndromes.

Many medical and neurologic disorders cause psychosis with delusions. The pathophysiology of this final common pathway may shed light on idiopathic psychotic disorders such as schizophrenia. By focusing on the "basal ganglia-thalamocortical" and "corticostriatal-thalamocortical" loops that connect limbically related cortical regions with the mesolimbic-mesostriatal dopamine system we can view the neural network that may produce delusional thinking when its restitutive function fails. Given its importance in the memory system of the medial temporal lobe, as the recipient of the emotional valencing from the amygdala, and as a key "loop" structure for cognitive functional integrity, the hippocampus may be a nodal area in the development of rational as opposed to delusional thinking.

Patient delay in cancer. A view from the crisis model.

Despite widespread cancer awareness programs, deleterious delays in seeking diagnosis and care for cancer are as prominent now as as they were 50 years ago. These delays may be seen as attempts to resolve or postpone the crisis brought on an individual by the suspicion of terminal illness. The use of denial-like processes in the cognitive appraisal employed to assess this crisis is influenced by a variety of personal, social, and physical factors. Case material is examined to discuss the integration of these factors by the crisis model of physical illness and to examine the implications of such an approach for earlier detection and treatment of cancer.

Presbyophrenia: a possible subtype of dementia.

Presbyophrenia is characterized by memory impairment, disorientation, confabulation, hypomanic features, and a preserved social facade. These occur in the absence of prior history of alcoholism or affective illness. We present three cases with presbyophrenia and suggest that the syndrome is a recognizable subtype of dementia, possibly related to disruption of aminergic pathways in frontal and subcortical structures.

Aspirin inhibits granulocyte and monocyte adherence to saphenous vein endothelia in a process not mediated by nitric oxide.

We examined the effects of aspirin on human immunocyte adherence to human saphenous vein preparations in vitro. Monocytes and granulocytes were analyzed by phase-contrast microscopy in conjunction with a time-lapse video recording system for cell counting in the medium. Saphenous vein samples taken from five volunteer subjects during their elective coronary artery bypass grafting procedures were used for an in vitro experiment in which each subject's immune cells were added to his/her respective endothelial tissues. In addition, aspirin or morphine was added to the preparations. After 30 min the endothelium and the medium were examined for cell numbers using feature color detection software. The endothelium exposed to a 10 min preincubation with 10 mmol/l aspirin was found to have significantly fewer monocytes and granulocytes attached. The saphenous vein preparations were examined for nitric oxide (NO) release using an NO-selective amperometric microprobe. Aspirin at its immunocyte inhibitory concentrations did not induce NO release from the endothelium, whereas morphine, which is known to stimulate NO production by endothelium, did so. These findings demonstrate that the administration of aspirin in high doses can diminish human granulocyte and monocyte adherence to saphenous vein endothelium in vitro through an NO-independent mechanism.