Neurological, neuropsychiatric and neurodevelopmental complications of COVID-19.

Although COVID-19 is predominantly a respiratory disease, it is known to affect multiple organ systems. In this article, we highlight the impact of SARS-CoV-2 (the coronavirus causing COVID-19) on the central nervous system as there is an urgent need to understand the longitudinal impacts of COVID-19 on brain function, behaviour and cognition. Furthermore, we address the possibility of intergenerational impacts of COVID-19 on the brain, potentially via both maternal and paternal routes. Evidence from preclinical models of earlier coronaviruses has shown direct viral infiltration across the blood-brain barrier and indirect secondary effects due to other organ pathology and inflammation. In the most severely ill patients with pneumonia requiring intensive care, there appears to be additional severe inflammatory response and associated thrombophilia with widespread organ damage, including the brain. Maternal viral (and other) infections during pregnancy can affect the offspring, with greater incidence of neurodevelopmental disorders, such as autism, schizophrenia and epilepsy. Available reports suggest possible vertical transmission of SARS-CoV-2, although longitudinal cohort studies of such offspring are needed. The impact of paternal infection on the offspring and intergenerational effects should also be considered. Research targeted at mechanistic insights into all aspects of pathogenesis, including neurological, neuropsychiatric and haematological systems alongside pulmonary pathology, will be critical in informing future therapeutic approaches. With these future challenges in mind, we highlight the importance of national and international collaborative efforts to gather the required clinical and preclinical data to effectively address the possible long-term sequelae of this global pandemic, particularly with respect to the brain and mental health.

Cerebrospinal Fluid Analysis in Rheumatological Diseases with Neuropsychiatric Complications and Manifestations: A Narrative Review.

The analysis of cerebrospinal fluid (CSF) remains a valuable diagnostic tool in the evaluation of inflammatory and infectious conditions involving the brain, spinal cord, and meninges. Since many rheumatic inflammatory diseases can involve the central and peripheral nervous system, the aims of this narrative review were to summarize the latest evidence on the use of CSF analysis in the field of neuropsychiatric manifestations of rheumatic diseases. Routine CSF parameters were taken into consideration for this review: appearance; total protein and cellular content (pleocytosis); lactate and/or glucose; CSF/serum albumin quotient; intrathecal synthesis of IgG. Data regarding the role of CSF analysis in the clinical management of neuropsychiatric systemic lupus erythematosus, primary Sjogren's syndrome, rheumatoid arthritis, and Behçet's syndrome are presented. Although no disease-specific picture has been identified, CSF analysis remains a useful diagnostic tool to confirm the presence of a neuro-inflammatory state or, conversely, to exclude the concomitant presence of other inflammatory/infectious diseases affecting the CNS in the context of systemic rheumatologic conditions.

Modeling methamphetamine use disorder in mammals: Sex differences in behavioral, biochemical, and transcriptional consequences.

Methamphetamine (METH) is the most commonly misused amphetamine-type stimulant throughout the globe. METH is very rewarding, and its misuse can lead to a diagnosis of METH use disorder (MUD). Although METH use is observed in both sexes, there are, however, reported differences in the clinical manifestations of METH use and its consequences. These observations indicate the need for more research on the long-term sex-dependent consequences of METH taking in both preclinical and clinical settings. In effect, sex is a biological variable that can impact conclusions drawn from various basic and clinical studies. Thus, the present chapter provides a succinct review of the current state of the research on METH and its sex-associated consequences. In addition to behavioral and cognitive aspects of METH use, we discuss METH-induced changes in neurotransmitter systems and structures in the brain. Thus, the book chapter serves to highlight the significance of sex as a critical element that needs to be considered during discussions of novel therapeutic approaches to MUD.

Oxidative Stress in the Pathogenesis of Oral Cancer.

Oxidative stress, arising from an imbalance between reactive oxygen species (ROS) and antioxidants, contributes significantly to oral cancer such as oral squamous cell carcinoma (OSCC) initiation, promotion, and progression. ROS, generated both internally and externally, induce cellular damage including DNA mutations and lipid peroxidation, fostering oncogene activation and carcinogenesis. The objective of this review was to cover and analyze the interplay between ROS and antioxidants, influencing the key processes such as cell proliferation, apoptosis, and angiogenesis, shaping the trajectory of OSCC development. Despite the promise of antioxidants to halt cancer progression and mitigate oxidative damage, their therapeutic efficacy remains debated. The conducted literature search highlighted potential biomarkers that indicate levels of oxidative stress, showing promise for the early detection and monitoring of OSCC. Furthermore, melatonin has emerged as a promising adjunct therapy for OSCC, exerting antioxidant and oncostatic effects by modulating tumor-associated neutrophils and inhibiting cancer cell survival and migration. In addition, this review aims to shed light on developing personalized therapeutic strategies for patients with OSCC such as melatonin therapy, which will be discussed. Research is needed to elucidate the underlying mechanisms and clinical implications of oxidative stress modulation in the context of oral cancer.

Electrical injuries and outcomes: A retrospective review.

Electrical burns (EI) differ from other burn injuries in the immediate treatment given and delayed sequelae they manifest. This paper reviews our burn center's experience with electrical injuries. All patients with electrical injuries admitted from January 2002 to August 2019 were included. Demographics; admission, injury, and treatment data; complications, including infection, graft loss, and neurologic injury; pertinent imaging, neurology consultation, neuropsychiatric testing; and mortality were collected. Subjects were divided into those who were exposed to high (>1000 volts), low (<1000 volts), and unknown voltage. The groups were compared. P < 0.05 was considered significant. One hundred sixty-two patients with electrical injuries were included. Fifty-five suffered low voltage, 55 high voltage, and 52 unknown voltage injuries. High voltage injuries were more likely to be male (98.2% vs. 83.6% low voltage vs. 94.2% unknown voltage, p = 0.015), to experience loss of consciousness (69.1% vs. 23.6% vs. 33.3%, p < 0.001), cardiac arrest (20% vs. 3.6% vs. 13.4%, p = 0.032), and undergo amputation (23.6% vs. 5.5% vs. 8.2%, p = 0.024). No significant differences were observed in long-term neurological deficits. Twenty-seven patients (16.7%) were found to have neurological deficits on or after admission; 48.2% recovered, 33.3% persisted, 7.4% died, and 11.1% did not follow-up with our burn center. Electrical injuries are associated with protean sequelae. Immediate complications include cardiac, renal, and deep burns. Neurologic complications, while uncommon, can occur immediately or are delayed.

'Malaria Has Spoilt It': Malaria, Neuropsychiatric Complications, and Insanity in ex-Servicemen in Post-First World War Britain.

This article focuses on the cases of two British ex-servicemen who contracted malaria during or immediately after the First World War, were charged with murder in the 1920s, and pled insanity due to their malaria and long-term neuropsychiatric complications. One was found 'guilty but insane' and committed to Broadmoor Criminal Lunatic Asylum in June 1923, while the other was convicted and hanged in July 1927. It argues that, at a time when the medical community sought out the causes of mental disease in the physical body, medico-legal arguments about malaria and insanity were received inconsistently by inter-war British courts. Class, education, social status, institutional support and the nature of the crime all mattered, as they had in the diagnoses, treatment and trials of other ex-servicemen with psychiatric illnesses.

Psychiatric and neuropsychiatric issues in persons with COVID-19 infection: A case-control online study from India-Neorealist study.

Background: Many studies across the globe have evaluated the adverse mental health consequences of COVID-19 in patients who suffered from COVID-19 infection. However, a comparative study of persons who suffered from COVID-19 infection and those who witnessed the COVID-19 infection in their close relatives is lacking. Aims and Objectives: This study aims to compare the psychiatric morbidity in persons who suffered from COVID-19 infections, and those who witnessed the illness in one of their close relatives. Methods: In this cross-sectional online survey, 2,964 adult participants completed the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) Scale, Fear of COVID-19 Scale (FCS-19), Brief Resilient Coping Scale (BRCS), The Brief Resilience Scale (BRS) and a self-designed questionnaire to evaluate other neuropsychiatric complications. Results: Compared to the close relatives who had witnessed COVID-19 infection, participants who developed COVID-19 infection had a significantly higher prevalence of depression (34.6%), anxiety disorder (32.3%), and fear of COVID-19 infection (18.8%), which was significantly higher than that noted in close relatives. However, BRS coping score was not significantly different between the two groups. Overall, about one-third of the participants who developed COVID-19 infection had depression and one-third had anxiety disorders. One-fifth of the participants reported high fear, post-traumatic symptoms, and obsessive-compulsive symptoms, whereas one-sixth reported other neuropsychiatric manifestations. Conclusion: Patients who suffered from COVID-19 have a higher prevalence of depression, anxiety, and fear as compared to those to witnessed COVID-19 in relatives.

Association between COVID-19 and catatonia manifestation in two adolescents in Central Asia: Incidental findings or cause for alarm?

Catatonia is a rare neuropsychiatric syndrome that can accompany various medical conditions, including schizophrenia, autoimmune encephalitis, and infectious diseases. We present two cases of catatonia in males aged 12 and 17 years from Central Asia who tested positive for SARS-Cov-2 antibodies. Detailed medical assessments declined other potential precipitating factors, including schizophrenia or anti-NMDA receptor autoimmune encephalitis. FDG-PET in the younger patient demonstrated focal hypometabolism in left frontotemporal and right associative visual cortex, matching patterns previously seen in adults with catatonia. These isolated findings raise concerns about a possible causal relationship between COVID-19 infection and risk of catatonia manifestation in adolescents.

Reducing delirium and cognitive dysfunction after off-pump coronary bypass: A randomized trial.

BACKGROUND: Neuropsychiatric complications of surgical coronary revascularization are inconspicuous but frequent and clinically relevant. So far, attempts to reduce their occurrence, such as the introduction of off-pump coronary artery bypass (OPCAB) grafting method, have not brought the desired results. The aim of this trial was to determine whether using any of the 2 selected modifications of OPCAB could decrease the incidence of these undesired sequelae. METHODS: In this single-center, assessor- and patient-blinded, superiority, randomized controlled trial, 192 patients scheduled for elective isolated OPCAB were randomized to 3 parallel arms. The control arm underwent "conventional" OPCAB with vein grafts. The first study arm underwent anaortic OPCAB (ANA) with total arterial revascularization. The second study arm underwent OPCAB with vein grafts using carbon dioxide surgical field flooding (CO2FF). Outcomes included the incidence of postoperative delirium (PD) and early postoperative cognitive dysfunction (ePOCD). RESULTS: The incidence of PD was 35.9% in the control (OPCAB) arm, 32.8% in the CO2FF arm, and 12.5% in the ANA arm (χ2 [2, N = 191] = 10.17; P = .006). Post hoc tests revealed that the incidence of PD in the ANA arm differed from that in the OPCAB arm (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.09-0.68; P = .002). The incidence of ePOCD was 34.4% in the OPCAB arm, 28.1% in the CO2FF arm, and 9.5% in the ANA arm (χ2 [2, N = 191] = 11.58; P = .003). Post hoc tests revealed that the incidence of ePOCD differed between the ANA and OPCAB arms (OR, 0.20; 95% CI, 0.06-0.58; P < .001). CONCLUSIONS: Performing ANA significantly decreases the incidence of PD and ePOCD compared with "conventional" OPCAB with vein grafts, whereas CO2FF is inconsequential in this regard. These results, which probably reflect decreased delivery of embolic load to the brain in ANA, may have practical applicability in daily practice to improve clinical outcomes.

Neurobehavioral consequences of small molecule-drug immunosuppression.

60 years after the first successful kidney transplantation in humans, transplant patients have decent survival rates owing to a broad spectrum of immunosuppressive medication available today. Not only transplant patients, but also patients with inflammatory autoimmune diseases or cancer benefit from these life-saving immunosuppressive and anti-proliferative medications. However, this success is gained with the disadvantage of neuropsychological disturbances and mental health problems such as depression, anxiety and impaired quality of life after long-term treatment with immunosuppressive drugs. So far, surprisingly little is known about unwanted neuropsychological side effects of immunosuppressants and anti-proliferative drugs from the group of so called small molecule-drugs. This is partly due to the fact that it is difficult to disentangle whether and to what extent the observed neuropsychiatric disturbances are a direct result of the patient's medical history or of the immunosuppressive treatment. Thus, here we summarize experimental as well as clinical data of mammalian and human studies, with the focus on selected small-molecule drugs that are frequently employed in solid organ transplantation, autoimmune disorders or cancer therapy and their effects on neuropsychological functions, mood, and behavior. These data reveal the necessity to develop immunosuppressive and anti-proliferative drugs inducing fewer or no unwanted neuropsychological side effects, thereby increasing the quality of life in patients requiring long term immunosuppressive treatment. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'.

The Story of "Speed" from "Cloud Nine" to Brain Gain.

The substituted amphetamines have had a checkered medical history intertwined with a sensational cultural history. Mankind's insatiable fascination with speed has led to widespread misuse sometimes with disastrous neurological and psychiatric consequences that may cause a permanent harm but their potential to enhance cognition should not be dismissed or forgotten. Further, smarter research could perhaps still lead to an expanded beneficial role for stimulant use in modern society.