Brain Health After COVID-19, Pneumonia, Myocardial Infarction, or Critical Illness.

Importance: Brain health is most likely compromised after hospitalization for COVID-19; however, long-term prospective investigations with matched control cohorts and face-to-face assessments are lacking. Objective: To assess whether long-term cognitive, psychiatric, or neurological complications among patients hospitalized for COVID-19 differ from those among patients hospitalized for other medical conditions of similar severity and from healthy controls. Design, Setting, and Participants: This prospective cohort study with matched controls was conducted at 2 academic hospitals in Copenhagen, Denmark. The case cohort comprised patients with COVID-19 hospitalized between March 1, 2020, and March 31, 2021. Control cohorts consisted of patients hospitalized for pneumonia, myocardial infarction, or non-COVID-19 intensive care-requiring illness between March 1, 2020, and June 30, 2021, and healthy age- and sex-matched individuals. The follow-up period was 18 months; participants were evaluated between November 1, 2021, and February 28, 2023. Exposures: Hospitalization for COVID-19. Main Outcomes and Measures: The primary outcome was overall cognition, assessed by the Screen for Cognitive Impairment in Psychiatry (SCIP) and the Montreal Cognitive Assessment (MoCA). Secondary outcomes were executive function, anxiety, depressive symptoms, and neurological deficits. Results: The study included 345 participants, including 120 patients with COVID-19 (mean [SD] age, 60.8 [14.4] years; 70 men [58.3%]), 125 hospitalized controls (mean [SD] age, 66.0 [12.0] years; 73 men [58.4%]), and 100 healthy controls (mean [SD] age, 62.9 [15.3] years; 46 men [46.0%]). Patients with COVID-19 had worse cognitive status than healthy controls (estimated mean SCIP score, 59.0 [95% CI, 56.9-61.2] vs 68.8 [95% CI, 66.2-71.5]; estimated mean MoCA score, 26.5 [95% CI, 26.0-27.0] vs 28.2 [95% CI, 27.8-28.6]), but not hospitalized controls (mean SCIP score, 61.6 [95% CI, 59.1-64.1]; mean MoCA score, 27.2 [95% CI, 26.8-27.7]). Patients with COVID-19 also performed worse than healthy controls during all other psychiatric and neurological assessments. However, except for executive dysfunction (Trail Making Test Part B; relative mean difference, 1.15 [95% CI, 1.01-1.31]), the brain health of patients with COVID-19 was not more impaired than among hospitalized control patients. These results remained consistent across various sensitivity analyses. Conclusions and Relevance: This prospective cohort study suggests that post-COVID-19 brain health was impaired but, overall, no more than the brain health of patients from 3 non-COVID-19 cohorts of comparable disease severity. Long-term associations with brain health might not be specific to COVID-19 but associated with overall illness severity and hospitalization. This information is important for putting understandable concerns about brain health after COVID-19 into perspective.

Frequency of Neurological Diseases After COVID-19, Influenza A/B and Bacterial Pneumonia.

Introduction: COVID-19 might affect the incidence of specific neurological diseases, but it is unknown if this differs from the risk following other infections. Here, we characterized the frequency of neurodegenerative, cerebrovascular, and immune-mediated neurological diseases after COVID-19 compared to individuals without COVID-19 and those with other respiratory tract infections. Methods: This population-based cohort study utilized electronic health records covering ~50% of Denmark's population (n = 2,972,192). Between 02/2020 and 11/2021, we included individuals tested for COVID-19 or diagnosed with community-acquired bacterial pneumonia in hospital-based facilities. Additionally, we included individuals tested for influenza in the corresponding pre-pandemic period between 02/ 2018 and 11/2019. We stratified cohorts for in- and outpatient status, age, sex, and comorbidities. Results: In total, 919,731 individuals were tested for COVID-19, of whom 43,375 tested positive (35,362 outpatients, 8,013 inpatients). Compared to COVID-negative outpatients, COVID-19 positive outpatients had an increased RR of Alzheimer's disease (RR = 3.5; 95%CI: 2.2-5.5) and Parkinson's disease (RR = 2.6; 95%CI: 1.7-4.0), ischemic stroke (RR = 2.7; 95%CI: 2.3-3.2) and intracerebral hemorrhage (RR = 4.8; 95%CI: 1.8-12.9). However, when comparing to other respiratory tract infections, only the RR for ischemic stroke was increased among inpatients with COVID-19 when comparing to inpatients with influenza (RR = 1.7; 95%CI: 1.2-2.4) and only for those >80 years of age when comparing to inpatients with bacterial pneumonia (RR = 2.7; 95%CI: 1.2-6.2). Frequencies of multiple sclerosis, myasthenia gravis, Guillain-Barré syndrome and narcolepsy did not differ after COVID-19, influenza and bacterial pneumonia. Conclusion: The risk of neurodegenerative and cerebrovascular, but not neuroimmune, disorders was increased among COVID-19 positive outpatients compared to COVID-negative outpatients. However, except for ischemic stroke, most neurological disorders were not more frequent after COVID-19 than after other respiratory infections.

Global warming and neurological practice: systematic review.

BACKGROUND: Climate change, including global warming, will cause poorer global health and rising numbers of environmental refugees. As neurological disorders account for a major share of morbidity and mortality worldwide, global warming is also destined to alter neurological practice; however, to what extent and by which mechanisms is unknown. We aimed to collect information about the effects of ambient temperatures and human migration on the epidemiology and clinical manifestations of neurological disorders. METHODS: We searched PubMed and Scopus from 01/2000 to 12/2020 for human studies addressing the influence of ambient temperatures and human migration on Alzheimer's and non-Alzheimer's dementia, epilepsy, headache/migraine, multiple sclerosis, Parkinson's disease, stroke, and tick-borne encephalitis (a model disease for neuroinfections). The protocol was pre-registered with PROSPERO (2020 CRD42020147543). RESULTS: Ninety-three studies met inclusion criteria, 84 of which reported on ambient temperatures and nine on migration. Overall, most temperature studies suggested a relationship between increasing temperatures and higher mortality and/or morbidity, whereas results were more ambiguous for migration studies. However, we were unable to identify a single adequately designed study addressing how global warming and human migration will change neurological practice. Still, extracted data indicated multiple ways by which these aspects might alter neurological morbidity and mortality soon. CONCLUSION: Significant heterogeneity exists across studies with respect to methodology, outcome measures, confounders and study design, including lack of data from low-income countries, but the evidence so far suggests that climate change will affect the practice of all major neurological disorders in the near future. Adequately designed studies to address this issue are urgently needed, requiring concerted efforts from the entire neurological community.

The evolutionary origin of near-death experiences: a systematic investigation.

Near-death experiences are known from all parts of the world, various times and numerous cultural backgrounds. This universality suggests that near-death experiences may have a biological origin and purpose. Adhering to a preregistered protocol, we investigate the hypothesis that thanatosis, aka death-feigning, a last-resort defense mechanism in animals, is the evolutionary origin of near-death experiences. We first show that thanatosis is a highly preserved survival strategy occurring at all major nodes in a cladogram ranging from insects to humans. We then show that humans under attack by animal, human and 'modern' predators can experience both thanatosis and near-death experiences, and we further show that the phenomenology and the effects of the two overlap. In summary, we build a line of evidence suggesting that thanatosis is the evolutionary foundation of near-death experiences and that their shared biological purpose is the benefit of survival. We propose that the acquisition of language enabled humans to transform these events from relatively stereotyped death-feigning under predatory attacks into the rich perceptions that form near-death experiences and extend to non-predatory situations.

B Vitamins and Fatty Acids: What Do They Share with Small Vessel Disease-Related Dementia?

Many studies have been written on vitamin supplementation, fatty acid, and dementia, but results are still under debate, and no definite conclusion has yet been drawn. Nevertheless, a significant amount of lab evidence confirms that vitamins of the B group are tightly related to gene control for endothelium protection, act as antioxidants, play a co-enzymatic role in the most critical biochemical reactions inside the brain, and cooperate with many other elements, such as choline, for the synthesis of polyunsaturated phosphatidylcholine, through S-adenosyl-methionine (SAM) methyl donation. B-vitamins have anti-inflammatory properties and act in protective roles against neurodegenerative mechanisms, for example, through modulation of the glutamate currents and a reduction of the calcium currents. In addition, they also have extraordinary antioxidant properties. However, laboratory data are far from clinical practice. Many studies have tried to apply these results in everyday clinical activity, but results have been discouraging and far from a possible resolution of the associated mysteries, like those represented by Alzheimer's disease (AD) or small vessel disease dementia. Above all, two significant problems emerge from the research: No consensus exists on general diagnostic criteria-MCI or AD? Which diagnostic criteria should be applied for small vessel disease-related dementia? In addition, no general schema exists for determining a possible correct time of implementation to have effective results. Here we present an up-to-date review of the literature on such topics, shedding some light on the possible interaction of vitamins and phosphatidylcholine, and their role in brain metabolism and catabolism. Further studies should take into account all of these questions, with well-designed and world-homogeneous trials.

Semiology and Mechanisms of Near-Death Experiences.

PURPOSE OF REVIEW: Near-death experiences (NDEs) are conscious perceptual experiences, including self-related emotional, spiritual, and mystical experiences, occurring in close encounters with death or in non-life-threatening situations. The origin of NDEs remains unknown. Here, we review recent advances in the understanding of NDE semiology and pathophysiology. RECENT FINDINGS: Recent prospective studies confirm that NDEs reflect a spectrum of highly distinctive memories which are associated with negative or positive emotions and can be influenced by the nature of the causal event, but the temporal sequence with which these images unfold is variable. Some drugs, notably ketamine, may lead to experiences that are similar or even identical to NDEs. New models extend previous neural network theories and include aspects of evolutionary and quantum theories. Although the factual existence of NDEs is no longer doubted and the semiology well-described, a pathophysiological model that includes all aspects of NDEs is still lacking.

Automated pupillometry to detect command following in neurological patients: a proof-of-concept study.

BACKGROUND: Levels of consciousness in patients with acute and chronic brain injury are notoriously underestimated. Paradigms based on electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) may detect covert consciousness in clinically unresponsive patients but are subject to logistical challenges and the need for advanced statistical analysis. METHODS: To assess the feasibility of automated pupillometry for the detection of command following, we enrolled 20 healthy volunteers and 48 patients with a wide range of neurological disorders, including seven patients in the intensive care unit (ICU), who were asked to engage in mental arithmetic. RESULTS: Fourteen of 20 (70%) healthy volunteers and 17 of 43 (39.5%) neurological patients, including 1 in the ICU, fulfilled prespecified criteria for command following by showing pupillary dilations during ≥4 of five arithmetic tasks. None of the five sedated and unconscious ICU patients passed this threshold. CONCLUSIONS: Automated pupillometry combined with mental arithmetic appears to be a promising paradigm for the detection of covert consciousness in people with brain injury. We plan to build on this study by focusing on non-communicating ICU patients in whom the level of consciousness is unknown. If some of these patients show reproducible pupillary dilation during mental arithmetic, this would suggest that the present paradigm can reveal covert consciousness in unresponsive patients in whom standard investigations have failed to detect signs of consciousness.

Cortical modulation of pupillary function: systematic review.

BACKGROUND: The pupillary light reflex is the main mechanism that regulates the pupillary diameter; it is controlled by the autonomic system and mediated by subcortical pathways. In addition, cognitive and emotional processes influence pupillary function due to input from cortical innervation, but the exact circuits remain poorly understood. We performed a systematic review to evaluate the mechanisms behind pupillary changes associated with cognitive efforts and processing of emotions and to investigate the cerebral areas involved in cortical modulation of the pupillary light reflex. METHODOLOGY: We searched multiple databases until November 2018 for studies on cortical modulation of pupillary function in humans and non-human primates. Of 8,809 papers screened, 258 studies were included. RESULTS: Most investigators focused on pupillary dilatation and/or constriction as an index of cognitive and emotional processing, evaluating how changes in pupillary diameter reflect levels of attention and arousal. Only few tried to correlate specific cerebral areas to pupillary changes, using either cortical activation models (employing micro-stimulation of cortical structures in non-human primates) or cortical lesion models (e.g., investigating patients with stroke and damage to salient cortical and/or subcortical areas). Results suggest the involvement of several cortical regions, including the insular cortex (Brodmann areas 13 and 16), the frontal eye field (Brodmann area 8) and the prefrontal cortex (Brodmann areas 11 and 25), and of subcortical structures such as the locus coeruleus and the superior colliculus. CONCLUSIONS: Pupillary dilatation occurs with many kinds of mental or emotional processes, following sympathetic activation or parasympathetic inhibition. Conversely, pupillary constriction may occur with anticipation of a bright stimulus (even in its absence) and relies on a parasympathetic activation. All these reactions are controlled by subcortical and cortical structures that are directly or indirectly connected to the brainstem pupillary innervation system.

Influence of Strategic Cortical Infarctions on Pupillary Function.

Objective: Cortical activity, including cognitive and emotional processes, may influence pupillary function. The exact pathways and the site of cortical pupillary innervation remain elusive, however. We investigated the effects of select cortical strokes, i.e. ischemic infarcts affecting the insular cortex and prefrontal eye field, on pupillary function. Methods: Seventy-four patients with acute ischemic stroke, consecutively admitted to our institution from March to July 2018, were assessed 24 h after endovascular recanalization therapy (i.e., day 2 after the stroke), using automated pupillometry. Stroke location and volume and clinical severity (estimated by the Alberta Stroke Program Early CT Score and National Institute of Health Stroke Scale) were recorded. We excluded patients with posterior circulation stroke, intracranial pathology other than ischemic stroke, midline shift on computed tomography exceeding 5 millimeters or a history of eye disease. Pupillometry data from 25 neurologically normal patients with acute myocardial infarction were acquired for control. Results: Fifty stroke patients after thrombectomy were included for analysis. Twenty-five patients (50%) had insular cortex or prefrontal eye field involvement (group 1, strategic infarcts); 25 patients had infarcts located in other cerebral areas (group 2, other infarcts). The pupillary light reflex, as measured by constriction velocity and maximal/minimal pupillary diameters, was within physiological limits in all patients, including controls. However, while pupillary size and constriction velocities were correlated in all subjects, the correlation of size and dilatation velocity was absent in right-hemispheric infarcts (left hemisphere infarcts, group 1 (r 2 = 0.15, p = 0.04), group 2 (r 2 = 0.41, p = 0.0007); right hemisphere infarcts, group 1 (r 2 = 0.008, p = 0.69); group 2 (r 2 = 0.12, p = 0.08); controls (r 2 = 0.29, p ≤ 0.0001). Conclusions: Cortical infarcts of the prefrontal eye field or insula do not impair the pupillary light reflex in humans. However, subtle changes may occur when the pupils dilate back to baseline, probably due to autonomic dysfunction. Replication is needed to explore the possible influence of hemispheric lateralization. We suggest that endovascular therapy for acute ischemic stroke may serve as a clinical research model for the study of acquired cortical lesions in humans.