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 (r2 = 0.15, p = 0.04), group 2 (r2 = 0.41, p = 0.0007); right hemisphere infarcts, group 1 (r2 = 0.008, p = 0.69); group 2 (r2 = 0.12, p = 0.08); controls (r2 = 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

Visual Behavior, Pupil Dilation, and Ability to Identify Emotions From Facial Expressions After Stroke

[EN] Social cognition is the innate human ability to interpret the emotional state of others from contextual verbal and non-verbal information, and to self-regulate accordingly. Facial expressions are one of the most relevant sources of non-verbal communication, and their interpretation has been extensively investigated in the literature, using both behavioral and physiological measures, such as those derived from visual activity and visual responses. The decoding of facial expressions of emotion is performed by conscious and unconscious cognitive processes that involve a complex brain network that can be damaged after cerebrovascular accidents. A diminished ability to identify facial expressions of emotion has been reported after stroke, which has traditionally been attributed to impaired emotional processing. While this can be true, an alteration in visual behavior after brain injury could also negatively contribute to this ability. This study investigated the accuracy, distribution of responses, visual behavior, and pupil dilation of individuals with stroke while identifying emotional facial expressions. Our results corroborated impaired performance after stroke and exhibited decreased attention to the eyes, evidenced by a diminished time and number of fixations made in this area in comparison to healthy subjects and comparable pupil dilation. The differences in visual behavior reached statistical significance in some emotions when comparing individuals with stroke with impaired performance with healthy subjects, but not when individuals post-stroke with comparable performance were considered. The performance dependence of visual behavior, although not determinant, might indicate that altered visual behavior could be a negatively contributing factor for emotion recognition from facial expressions.This study was funded by Conselleria de Educacion, Cultura y Deporte of Generalitat Valenciana of Spain (Project SEJI/2019/017), and Universitat Politecnica de Valencia (Grant PAID-10-18).Maza, A.; Moliner, B.; Ferri, J.; Llorens Rodríguez, R. (2020). Visual Behavior, Pupil Dilation, and Ability to Identify Emotions From Facial Expressions After Stroke. Frontiers in Neurology. 10:1-12. https://doi.org/10.3389/fneur.2019.01415S11210Nijsse, B., Spikman, J. M., Visser-Meily, J. M. A., de Kort, P. L. M., & van Heugten, C. M. (2019). Social cognition impairments are associated with behavioural changes in the long term after stroke. PLOS ONE, 14(3), e0213725. doi:10.1371/journal.pone.0213725Feldman, R. S., White, J. B., & Lobato, D. (1982). Social Skills and Nonverbal Behavior. 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Dementia and Geriatric Cognitive Disorders, 36(3-4), 179-196. doi:10.1159/000353440Babbage, D. R., Yim, J., Zupan, B., Neumann, D., Tomita, M. R., & Willer, B. (2011). Meta-analysis of facial affect recognition difficulties after traumatic brain injury. Neuropsychology, 25(3), 277-285. doi:10.1037/a0021908Milders, M., Fuchs, S., & Crawford, J. R. (2003). Neuropsychological Impairments and Changes in Emotional and Social Behaviour Following Severe Traumatic Brain Injury. Journal of Clinical and Experimental Neuropsychology, 25(2), 157-172. doi:10.1076/jcen.25.2.157.13642Genova, H. M., Genualdi, A., Goverover, Y., Chiaravalloti, N. D., Marino, C., & Lengenfelder, J. (2016). An investigation of the impact of facial affect recognition impairments in moderate to severe TBI on fatigue, depression, and quality of life. Social Neuroscience, 12(3), 303-307. doi:10.1080/17470919.2016.1173584Rigon, A., Voss, M. W., Turkstra, L. S., Mutlu, B., & Duff, M. C. (2018). Different aspects of facial affect recognition impairment following traumatic brain injury: The role of perceptual and interpretative abilities. Journal of Clinical and Experimental Neuropsychology, 40(8), 805-819. doi:10.1080/13803395.2018.1437120Rosenberg, H., McDonald, S., Dethier, M., Kessels, R. P. C., & Westbrook, R. F. (2014). Facial Emotion Recognition Deficits following Moderate–Severe Traumatic Brain Injury (TBI): Re-examining the Valence Effect and the Role of Emotion Intensity. Journal of the International Neuropsychological Society, 20(10), 994-1003. doi:10.1017/s1355617714000940Lancelot, C., & Gilles, C. (2018). How does visual context influence recognition of facial emotion in people with traumatic brain injury? Brain Injury, 33(1), 4-11. doi:10.1080/02699052.2018.1531308McDonald, S. (2013). Impairments in Social Cognition Following Severe Traumatic Brain Injury. Journal of the International Neuropsychological Society, 19(3), 231-246. doi:10.1017/s1355617712001506Vallat-Azouvi, C., Azouvi, P., Le-Bornec, G., & Brunet-Gouet, E. (2018). Treatment of social cognition impairments in patients with traumatic brain injury: a critical review. Brain Injury, 33(1), 87-93. doi:10.1080/02699052.2018.1531309Godin, B., Oishi, K., Oishi, K., Davis, C., Gomez, Y., Trupe, L., … Tippett, D. (2018). Impaired Recognition of Emotional Faces after Stroke Involving Right Amygdala or Insula. Seminars in Speech and Language, 39(01), 087-100. doi:10.1055/s-0037-1608859Abbott, J. D., Cumming, G., Fidler, F., & Lindell, A. K. (2013). The perception of positive and negative facial expressions in unilateral brain-damaged patients: A meta-analysis. Laterality: Asymmetries of Body, Brain and Cognition, 18(4), 437-459. doi:10.1080/1357650x.2012.703206Abbott, J. D., Wijeratne, T., Hughes, A., Perre, D., & Lindell, A. K. (2014). The perception of positive and negative facial expressions by unilateral stroke patients. Brain and Cognition, 86, 42-54. doi:10.1016/j.bandc.2014.01.017Delazer, M., Sojer, M., Ellmerer, P., Boehme, C., & Benke, T. (2018). Eye-Tracking Provides a Sensitive Measure of Exploration Deficits After Acute Right MCA Stroke. Frontiers in Neurology, 9. doi:10.3389/fneur.2018.00359Lech, M., Kucewicz, M. T., & Czyżewski, A. (2019). Human Computer Interface for Tracking Eye Movements Improves Assessment and Diagnosis of Patients With Acquired Brain Injuries. Frontiers in Neurology, 10. doi:10.3389/fneur.2019.00006Spikman, J. M., Milders, M. V., Visser-Keizer, A. C., Westerhof-Evers, H. J., Herben-Dekker, M., & van der Naalt, J. (2013). Deficits in Facial Emotion Recognition Indicate Behavioral Changes and Impaired Self-Awareness after Moderate to Severe Traumatic Brain Injury. PLoS ONE, 8(6), e65581. doi:10.1371/journal.pone.0065581Knox, L., & Douglas, J. (2009). Long-term ability to interpret facial expression after traumatic brain injury and its relation to social integration. Brain and Cognition, 69(2), 442-449. doi:10.1016/j.bandc.2008.09.009Struchen, M. A., Clark, A. N., Sander, A. M., Mills, M. R., Evans, G., & Kurtz, D. (2008). Relation of executive functioning and social communication measures to functional outcomes following traumatic brain injury. NeuroRehabilitation, 23(2), 185-198. doi:10.3233/nre-2008-23208Ferro, J. M., Caeiro, L., & Santos, C. (2009). Poststroke Emotional and Behavior Impairment: A Narrative Review. Cerebrovascular Diseases, 27(1), 197-203. doi:10.1159/000200460Bortolon, C., Capdevielle, D., & Raffard, S. (2015). Face recognition in schizophrenia disorder: A comprehensive review of behavioral, neuroimaging and neurophysiological studies. Neuroscience & Biobehavioral Reviews, 53, 79-107. doi:10.1016/j.neubiorev.2015.03.006Harms, M. B., Martin, A., & Wallace, G. L. (2010). 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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\u2019s disease (AD) or small vessel disease dementia. Above all, two significant problems emerge from the research: No consensus exists on general diagnostic criteria\u2014MCI 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

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

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

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

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

Reduction in pediatric growth hormone deficiency and increase in central precocious puberty diagnoses during COVID 19 pandemics

11noBackground: While several studies have been published so far on the effect of COVID-19 pandemic on health care for non-COVID-19 diseases, to date no study evaluated the impact of the COVID-19 pandemic on the entire field of pediatric endocrinology. This study aimed to evaluate differences in pediatric endocrine stimulation tests after the advent of COVID-19 pandemics. Methods: Retrospective study with data collection for pediatric endocrine stimulation tests performed in 2019 and 2020 in a tertiary center. Results: Overall, 251 tests were performed on 190 patients in 2020, compared to 278 tests on 206 patients in 2019 (-10% tests; -8% children evaluated). A significant reduction was found in tests to diagnose growth hormone deficiency (GHD) (-35%), while LHRH tests increased (+22%). A reduction of 30% in GHD diagnosis was observed. Central precocious puberty (CPP) diagnosis increased by 38% compared to 2019, mainly in females. Conclusion: This study found a significant reduction of tests investigating GHD during COVID-19 pandemics. It also showed a clinically meaningful increase in cases of CPP in girls. These results suggest the need for families and pediatricians to monitor children's growth during isolation and enlighten new perspectives towards conditions associated with lockdown restrictions as increased screen time, social isolation, and children's anxiety as possible triggers of CPP.openopenMartina Peinkhofer; Benedetta Bossini; Arturo Penco; Manuela Giangreco; Maria Chiara Pellegrin; Viviana Vidonis; Giada Vittori; Nicoletta Grassi; Elena Faleschini; Egidio Barbi; Gianluca TornesePeinkhofer, Martina; Bossini, Benedetta; Penco, Arturo; Giangreco, Manuela; Pellegrin, MARIA CHIARA; Vidonis, Viviana; Vittori, Giada; Grassi, Nicoletta; Faleschini, Elena; Barbi, Egidio; Tornese, Gianluc