Pupillary Reaction Research Articles

Signs of life as a favorable predictor for non-shockable cardiac arrest undergoing extracorporeal cardiopulmonary resuscitation post non-shockable cardiac arrest

BackgroundWhen the initial rhythm of cardiac arrest is non-shockable, resuscitation outcomes tend to be unfavorable. However, signs of life (gasping, pupillary light reaction, or any form of body movement) have been suggested as favorable prognostic factors for patients with refractory cardiac arrest who are undergoing extracorporeal cardiopulmonary resuscitation (ECPR). This study determined whether signs of life are favorable neurological prognostic factors for patients undergoing ECPR post non-shockable cardiac arrest. Methods and resultsThis single-center retrospective study included 227 refractory out-of-hospital cardiac-arrest patients who had undergone ECPR, divided into four groups according to shockability of initial cardiac rhythms and presence of signs of life. Initial cardiac rhythms were shockable in 154 patients (67.8 %) and non-shockable in 73 (32.2). Favorable neurological outcomes were observed in 4.1 %, 48.2 %, 0.0 %, and 38.7 % of patients with shockable rhythm without signs of life, shockable rhythm with signs of life, non-shockable rhythm without signs of life, and non-shockable rhythm with signs of life, respectively, with significant differences. Multivariate logistic regression analysis showed an independent association of signs of life during resuscitation with favorable neurological outcomes. The adjusted odds ratios for patients with shockable and non-shockable rhythm with signs of life were 34.33 and 96.51, respectively, compared with those without signs of life. ConclusionsSigns of life during resuscitation were favorable prognostic factors in patients with refractory cardiac arrest and non-shockable rhythm. When these patients are considered for ECPR, the status of signs of life during resuscitation may facilitate the decision to perform ECPR.

Ocular manifestations in neurofibromatosis: A case series

Background: A collection of inherited diseases known as neurofibromatosis (NF) are distinguished by a broad spectrum of clinical manifestations. A genetic mutation on chromosome 17 (17q11.2) is the cause of NF type 1 (NF1), whereas a mutation on chromosome 22 (22q12.2) is the cause of NF type 2 (NF2). In NF1, ocular symptoms are more frequent. Patients with NF1 commonly appear with globe enlargement, glaucoma, and orbital facial involvement. Palpebral neurofibromas have the potential to grow extensively and, in rare instances, develop into malignant tumors. Optic nerve gliomas can result in strabismus and proptosis. Up to 80% of patients with NF2 may experience early-onset cataracts, optic nerve hamartomas, and mixed pigment retinal and epithelial hamartomas. Case presentation: We present four cases of neurofibromatosis, each displaying typical clinical features of the disorder. · Case 1: A 28-year-old male presented with headaches, reduced vision, and multiple tiny discolorations in both eyes for six months. Examination revealed multiple hyperpigmented skin lesions (2-5 mm) across his body, and ocular assessment showed normal pupillary reactions and distant vision of 6/6 in both eyes. Slit-lamp examination identified multiple dome-shaped lesions on the iris, consistent with Lisch nodules. · Case 2: A 42-year-old female experienced reduced vision for six months and skin lesions for five years. Examination revealed multiple discrete skin-colored papules and café-au-lait macules on her hands. Her vision was 6/12 in both eyes, with normal pupillary reactions. Slit-lamp findings were also consistent with Lisch nodules. o Case 3: A 48-year-old male reported vision loss in both eyes over two months, accompanied by swelling of the right upper eyelid, which was increasing in size. Lisch nodules were found on the iris of the left eye, and he was diagnosed with typical NF. o Case 4: A 38-year-old male presented with diminished vision. Slit-lamp examination revealed multiple dome-shaped lesions on the iris, suggesting Lisch nodules, along with skin lesions on the face and other body areas Conclusion: Managing neurofibromatosis requires a multidisciplinary approach, involving close collaboration between healthcare providers. Monitoring visual prognosis, enrolling patients in clinical trials, and regular disease monitoring are essential steps in managing the condition.

Emotional contagion to vocal smile revealed by combined pupil reactivity and motor resonance

The interplay between the different components of emotional contagion (i.e. emotional state and facial motor resonance), both during implicit and explicit appraisal of emotion, remains controversial. The aims of this study were (i) to distinguish between these components thanks to vocal smile processing and (ii) to assess how they reflect implicit processes and/or an explicit appraisal loop. Emotional contagion to subtle vocal emotions was studied in 25 adults through motor resonance and Autonomic Nervous System (ANS) reactivity. Facial expressions (fEMG: facial electromyography) and pupil dilation were assessed during the processing and judgement of artificially emotionally modified sentences. fEMG revealed that Zygomaticus major was reactive to the perceived valence of sounds, whereas the activity of Corrugator supercilii reflected explicit judgement. Timing analysis of pupil dilation provided further insight into both the emotional state and the implicit and explicit processing of vocal emotion, showing earlier activity for emotional stimuli than for neutral stimuli, followed by valence-dependent variations and a late judgement-dependent increase in pupil diameter. This innovative combination of different electrophysiological measures shed new light on the debate between central and peripherical views within the framework of emotional contagion.

FEATURES OF FUNCTIONAL DIAGNOSTICS OF OPTIC NERVE DAMAGE IN CASE OF HEAD INJURY

Introduction. Traumatic optic nerve damage is a rare complication of a head injury. Symptoms of primary damage appear at the time of first diagnostic in the early period and mask TON’s signs. Understanding of visual disturbances for the patient comes in a later period, when recovery is limited due to the irreversibility of the received injuries. Difficulties of early diagnosis of optic nerve damage in case of head trauma encourage the search for new, more informative methods. The aim of the study was to analyze the functional manifestations of the optic nerve damage in case of head injuries with different localization. Materials and methods. 366 cases (732 eyes) of patients with traumatic optic neuropathy (TON) were studied according to archival data in the period from 2014 to 2019. The control group consisted of 58 practically healthy persons (116 eyes). All patients were divided into three groups: A group - patients with traumatic brain injury (TBI) was 120 persons, B group - patients with craniofacial injury (CFI) - 118 persons and C group - with combined injuries - 128 injured. The degree of optic nerve damage was assessed using visometry, pupillometry, and perimetry. Results. In case of craniocerebral injury, decrease of visual acuity with an average value of 0.92±0.06 corresponded to degrees 0 (93%) and I (7%). In the case of craniofacial trauma, according to the research, visual acuity decreased to 0.76±0.13 (by 0.24, 24% compared to the control group, p<0.05). The first degree (23%) and the second degree (7%) were determined. With a combined primary head injury, visual acuity decreased to 0.42±0.21 (by 0.58, 58%, compared to the control group, p<0.05). One third were patients with I, II and III degrees of visual impairment. The use of static perimetry made it possible to detect damage to the optic nerve in patients with 0 degrees of reduced visual acuity. At the same time, 88% of patients of A group (n=120) had 0A class, 23% of B group (n=118) had 0B class, and in C group (n=122) there was almost no. The relative afferent pupillary defect’s test was negative at 0A group of vision loss, but the pupil cycle speed (PSC) was reduced in all patients. This confirms damage to the optic nerve in patients with high visual acuity This study showed that patients with TBI had high visual acuity in 93% of cases, The visual acuity was around 0.5-1.0, but sensitivity in the central part of the visual field decreased by 12 times, and the pupil reaction rate decreased by 55% compared to the control group. In case of craniofacial trauma (B group), visual acuity decreased to 0.76±0.13 (by 0.24, 24% compared to the control group, p<0.05). I degree (23%) and II degree (7%) decrease of visual acuity was determined. As for the sensitivity in the central part of the visual field, it was 46.59% lower than in the A group. In patients with a combined injury of the head and face, a third of the injured had visual acuity less than 0.1, which is not found in other variants of injury. Conclusions. Analysis showed that severity of optic nerve damage depends on localization of the head injury. The use of static perimetry and pupillometry is important for the early diagnosis of TON in conditions with high visual acuity when other symptoms are weak or not amenable to examination.

7643 Acute blindness due to Metformin associated lactic acidosis

Abstract Disclosure: K.N. Pereira: None. K. Desai: None. T. Khan: None. S. Yong: None. Metformin, one of the most commonly prescribed oral hypoglycemic agents, effectively lowers basal and postprandial blood glucose. However, Metformin carries a black box warning for lactic acidosis, which is more common in setting of liver and kidney dysfunction. With an incidence rate of ∼ 4.3 cases per 100,000 patient-years, Metformin associated lactic acidosis (MALA) can present with nausea, vomiting, diarrhea, encephalopathy, hypothermia, respiratory failure and hypotension. Blindness is a rarely reported outcome of MALA. We present a case of a 48 year old intellectually disabled female with a history of type 2 diabetes (on Metformin) who presented with progressive encephalopathy insetting of intractable nausea and vomiting with poor oral intake, since starting lisinopril & rosuvastatin for newly diagnosed hypertension and hyperlipidemia. She was encephalopathic, hypothermic, hypotensive, tachycardic and tachypneic. Labs were notable for leukocytosis, AKI, hyperkalemia, elevated anion gap metabolic acidosis with a lactate of 13.6 and elevated lipase. She also tested positive for Influenza A. CT head showed no acute intracranial abnormality. CT chest, abdomen & pelvis was concerning for aspiration, multifocal pneumonia or a combination of both as well as acute interstitial pancreatitis. She was admitted to the ICU for further management including hemodialysis. She continued to have improving but persistent lactic acidosis despite multiple dialysis sessions. On day 5 of ICU stay, with resolution of her encephalopathy, she reported new onset complete bilateral painless vision loss. General eye and neurologic exam was unrevealing except for sluggishly reactive pupils to light. MRI brain showed an new acute 2 mm lacunar infarct in the right temporal lobe. Neurology ruled out stroke as the cause for her vision loss. Emergent ophthalmology evaluation revealed no retinopathy, macular edema, acute glaucoma or thromboembolic event. The new onset vision loss was suspected to be due to MALA due to persistent metabolic disturbances. Some animal studies have shown that retinal horizontal cells are sensitive to low pH, resulting in interruption of signal transmission to the visual neurons and consequent blindness. The presence of factors like metformin metabolites may contribute to impaired function of retinal cells.On extensive literature review it was noted that only 5 cases of vision loss associated with MALA have been reported. However, in these cases, vision loss was transient and reversed following correction of acidosis with dialysis. Our case highlights a rare consequence of MALA, which can be irreversible and cause lifelong disability. Presentation: 6/1/2024

8158 Transient Blindness In Metformin-Associated Lactic Acidosis

Abstract Disclosure: Y. Abouelkheer: None. A. Nasir: None. M. Ibrahem: None. Transient Blindness in Metformin-associated Lactic Acidosis Background: Metformin-associated lactic acidosis (MALA) is a rare side effect of metformin use. MALA can result in acute transient blindness in patients with severe metabolic derangements. Clinical Case: A 62-year-old woman presented with severe diarrhea, poor oral intake, malaise, and vomiting on a background of metformin-treated type 2 diabetes mellitus. Laboratory investigations showed bicarbonate <2 mmol/L, anion gap 48 mmol/L, lactic acid 20.5 mmol/L, serum osmolality 352 mOsm/kg, negative urine toxicology screen, and positive SARS-CoV-2. In the emergency department, the patient developed sudden onset bilateral vision loss. The examination was remarkable for complete vision loss bilaterally in all fields, associated with minimally reactive pupils and spontaneous ocular movements with an otherwise unrevealing neurological examination. Computed Tomography (CT) of the brain with stroke protocol showed no evidence of acute intracranial process. CT angiogram of the brain and neck showed patent intracranial and cervical vasculature without high-grade stenosis, large vessel occlusion, or aneurysm. While receiving medical management with intravenous fluid resuscitation and sodium bicarbonate supplementation, the patient had a spontaneous return of vision with no additional neurological complications or deficits. The severe metabolic derangements were associated with distributive shock, requiring admission to the intensive care unit for urgent hemodialysis, pressor support, empiric antibiotics, and stress-dose steroids. Shortly after the patient’s only hemodialysis session, we noted the resolution of her critical metabolic disturbances, renal failure, and shock state. Laboratory investigations post-dialysis showed bicarbonate 12 mmol/L, anion gap 36 mmol/L, and lactic acid 10.5 mmol/L. Follow-up MRI showed chronic lacunar infarct of the left basal ganglia, and she was discharged home six days later. Conclusion: Transient blindness in MALA can mimic acute neurovascular events. Prompt correction of metabolic derangements can aid in reversing systemic symptoms and blindness. Reference: DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016;65(2):20-29. doi:10.1016/j.metabol.2015.10.014 Presentation: 6/2/2024

The MOST (Mortality Score for TBI): A Novel Prediction Model Beyond CRASH-Basic and IMPACT-Core for Isolated Traumatic Brain Injury

BackgroundDue to significant injury heterogeneity, outcome prediction following traumatic brain injury (TBI) is challenging. This study aimed to develop a simple model for high-accuracy mortality risk prediction after TBI. Study DesignData from the American College of Surgeons (ACS) Trauma Quality Program (TQP) from 2019 to 2021 was used to develop a summary score based on age, the Glasgow Coma Scale (GCS) component subscores, and pupillary reactivity data. We then compared the predictive accuracy to that of the Corticosteroid Randomisation After Significant Head Injury Trial (CRASH)-Basic and International Mission for Prognosis and Analysis of Clinical Trial in TBI (IMPACT)-Core models. Two separate series of sensitivity analyses were conducted to further assess our model's generalizability. We evaluated predictive performance of the models with discrimination [the area under the receiver-operating characteristic curves (AUC), sensitivity, specificity] and calibration (Brier score). Discriminative ability was compared with DeLong tests. Results259,404 patients were included in the present study (mean age, 60 years; 93,495 (36%) female). The mortality score after TBI (MOST) model (AUC = 0.875) had better discrimination (DeLong test p values < 0.00001) than CRASH-Basic (AUC = 0.837) and IMPACT-Core (AUC = 0.821) models, and superior calibration (MOST = 0.02729, CRASH-Basic = 0.02962, IMPACT-Core = 0.02962) in predicting in-hospital mortality. The MOST model similarly outperformed in predicting 3-, 7-, 14-, and 30-day mortality. ConclusionThe MOST model can be rapidly calculated and outperforms two widely used models for predicting mortality in TBI patients. It utilizes a larger, contemporaneous dataset that reflects modern trauma care.

Hypertension and its correlation with autonomic nervous system dysfunction, heart rate variability and chronic inflammation

Objective This study investigates the relationship between hypertension, dysregulation of the autonomic nervous system, heart rate variability (HRV), and chronic inflammation. Methods We analysed a cohort of 50 hypertensive patients treated at the affiliated Hospital of Jianghan University. The average systolic and diastolic blood pressures (BPs) in this group were 155.26 and 95.32 mmHg, respectively. A control group of 50 healthy volunteers, undergoing routine physical examinations at the same hospital, was also analysed. Results The average systolic BP of the control group was 115.64 ± 10.27 mmHg, and the average diastolic BP was 75.33 ± 8.25 mmHg. In contrast, the experimental group exhibited an average systolic BP of 155.26 ± 20.13 mmHg and an average diastolic BP of 95.32 ± 12.16 mmHg. Both systolic and diastolic BPs were significantly higher in the hypertensive group (p < 0.05). The experimental group also demonstrated reduced HRV and skin conductance response, alongside increased BP variability (BPV), urinary epinephrine levels and prolonged pupillary light reaction time compared to controls (p < 0.05). Notably, Standard Deviation of Normal to Normal Intervals (SDNN) and Root Mean Square of Successive Differences (RMSSD) values were significantly lower in the experimental group (p < 0.05). Furthermore, levels of inflammatory markers such as CRP, TNF-α, IL-6 and IL-1β were markedly elevated in hypertensive patients (p < 0.05). Negative correlations were observed between systolic and diastolic BP with HRV metrics, while positive correlations were found between BP and BPV as well as urinary adrenaline levels. Conclusions The findings indicate that hypertension is closely associated with autonomic nervous system dysfunction, reduced HRV and increased chronic inflammation. A comprehensive approach to hypertension management should integrate these interrelated physiological and pathological mechanisms, with potential therapeutic interventions targeting autonomic function and inflammatory states.

Suspected intracranial hypertension in COVID-19 patients with severe respiratory failure.

COVID-19 patients may exhibit neurological symptoms due to direct viral damage, systemic inflammatory syndrome, or treatment side effects. Mechanical ventilation in patients with severe respiratory failure often requires sedation and neuromuscular blockade, hindering thorough clinical examinations. This study aimed to investigate neurological involvement through clinical and noninvasive techniques and to detect signs of intracranial hypertension in these patients. We conducted a prospective observational study on mechanically ventilated COVID-19 adult patients admitted to our ICU, following standard of care protocols for ventilation and permissive hypercapnia. Data were collected at three time points: admission day (T1), day seven (T7), and day fourteen (T14). At each time point, patients underwent multimodal noninvasive neurological monitoring, including clinical examination, pupillary reactivity, transcranial color doppler of the middle cerebral artery (MCA), and optic nerve sheath diameter (ONSD) assessed via ultrasound (US). Head computer tomography (CT) was performed at T1 and T14. A limited subset of patients had a follow-up examination six months after ICU discharge. Seventy-nine patients were recruited; most were under deep sedation and neuromuscular blockade at T1. Pupillary size, symmetry, and reactivity were normal, as was the MCA mean velocity. However, ONSD, assessed by both US and CT, appeared enlarged, suggesting raised intracranial pressure (ICP). In a subgroup of 12 patients, increased minute ventilation was associated with a significant decrease in US-ONSD, corresponding to a drop in paCO2. At follow-up, twelve patients showed no long-term neurological sequelae, and US-ONSD was decreased in all of them. In this cohort, enlarged ONSD was detected during non-invasive neurological monitoring, suggesting a raised ICP, with hypercapnia playing a prominent role. Further studies are needed to explore ONSD behavior in other samples of mechanically ventilated, hypercapnic patients.

The ventromedial prefrontal cortex plays an important role in implicit emotion regulation: A focality-optimized multichannel tDCS study in anxiety individuals.

The regulation of emotions is a crucial facet of well-being and social adaptability, with explicit strategies receiving primary attention in prior research. Recent studies, however, emphasize the role of implicit emotion regulation, particularly implicating the ventromedial prefrontal cortex (VMPFC) in association with its implementation. This study delves into the nuanced role of the VMPFC through focality-optimized multichannel transcranial direct current stimulation (tDCS), shedding light on its causal involvement in implicit reappraisal. The primary goal was to evaluate the effectiveness of VMFPC-targeted tDCS and elucidate its role in individuals with high trait anxiety. Participants engaged in implicit and explicit emotion regulation tasks during multichannel tDCS targeting the VMPFC. The outcome measures encompassed negative emotion ratings, pupillary diameter, and saccade count, providing a comprehensive evaluation of emotion regulation efficiency. The intervention exhibited a notable impact, resulting in significant reductions in negative emotion ratings and pupillary reactions during implicit reappraisal, highlighting the indispensable role of the VMPFC in modulating emotional responses. Notably, these effects demonstrated sustained efficacy up to 1 day postintervention. This study underscores the potency of VMPFC-targeted multichannel tDCS in augmenting implicit emotion regulation. This not only contributes insights into the neural mechanisms of emotion regulation but also suggests innovative therapeutic avenues for anxiety disorders. The findings present a promising trajectory for future mood disorder interventions, bridging the gap between implicit emotion regulation and neural stimulation techniques.

Pupil dilation reflects the social and motion content of faces.

Human facial features (eyes, nose, and mouth) allow us to communicate with others. Observing faces triggers physiological responses, including pupil dilation. Still, the relative influence of social and motion content of a visual stimulus on pupillary reactivity has never been elucidated. A total of 30 adults aged 18-33 years old were recorded with an eye tracker. We analysed the event-related pupil dilation in response to stimuli distributed along a gradient of social salience (non-social to social, going from objects to avatars to real faces) and dynamism (static to micro- to macro-motion). Pupil dilation was larger in response to social (faces and avatars) compared to non-social stimuli (objects), with surprisingly a larger response for avatars. Pupil dilation was also larger in response to macro-motion compared to static. After quantifying each stimulus' real quantity of motion, we found that the higher the quantity of motion, the larger the pupil dilated. However, the slope of this relationship was not higher for social stimuli. Overall, pupil dilation was more sensitive to the real quantity of motion than to the social component of motion, highlighting the relevance of ecological stimulations. Physiological response to faces results from specific contributions of both motion and social processing.

MRI and Clinical Variables for Prediction of Outcomes After Pediatric Severe Traumatic Brain Injury

Traumatic brain injury (TBI) is a leading cause of death and disability in children, and predicting functional outcome after TBI is challenging. Magnetic resonance imaging (MRI) is frequently conducted after severe TBI; however, the predictive value of MRI remains uncertain. To identify early MRI measures that predict long-term outcome after severe TBI in children and to assess the added predictive value of MRI measures over well-validated clinical predictors. This preplanned prognostic study used data from the Approaches and Decisions in Acute Pediatric TBI (ADAPT) prospective observational comparative effectiveness study. The ADAPT study enrolled 1000 consecutive children (aged <18 years) with severe TBI between February 1, 2014, and September 30, 2017. Participants had a Glasgow Coma Scale (GCS) score of 8 or less and received intracranial pressure monitoring. Magnetic resonance imaging scans performed as part of standard clinical care within 30 days of injury were collected at 24 participating sites in the US, UK, and Australia. Summary imaging measures were correlated with the Glasgow Outcome Scale-Extended for Pediatrics (GOSE-Peds), and the predictive value of MRI measures was compared with the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) core clinical predictors. Data collection, image analysis, and data analyses were completed in July 2023. Pediatric severe TBI with an MRI scan performed as part of clinical care. All measures were selected a priori. Magnetic resonance imaging measures included contusion, ischemia, diffuse axonal injury, intracerebral hemorrhage, and brainstem injury. Clinical predictors included the IMPACT core measures (GCS motor score and pupil reactivity). All models adjusted for age and sex. Outcome measures included the GOSE-Peds score obtained at 3, 6, and 12 months after injury. This study included 233 children with severe TBI who were enrolled at participating sites and had an MRI scan and preselected clinical predictors available. Their median age was 6.9 (IQR, 3.0-13.3) years, and more than half of participants (134 [57.5%]) were male. In a multivariable model including MRI measures and IMPACT core clinical variables, contusion volume (odds ratio [OR], 1.13; 95% CI, 1.02-1.26), brain ischemia (OR, 2.11; 95% CI, 1.58-2.81), brainstem lesions (OR, 5.40; 95% CI, 1.90-15.35), and pupil reactivity were each independently associated with GOSE-Peds score. Adding MRI measures to the IMPACT clinical predictors significantly improved model fit and discrimination between favorable and unfavorable outcomes compared with IMPACT predictors alone (area under the receiver operating characteristic curve, 0.77; 95% CI, 0.72-0.85 vs 0.67; 95% CI, 0.61-0.76 for GOSE-Peds score >3 at 6 months after injury). In this prognostic study of children with severe TBI, the addition of MRI measures significantly improved outcome prediction over well-established and validated clinical predictors. Magnetic resonance imaging should be considered in children with severe TBI to inform prognosis and may also promote stratification of patients in future clinical trials.

Opium tincture has anti-propulsive effects in patients with chronic diarrhea: a randomized, placebo-controlled, and cross-over trial

Objective Chronic diarrhea affects approximately 5% of the population. Opioids inhibit gastrointestinal motility, and opium tincture has shown anti-propulsive effects in healthy, but no controlled studies of its clinical efficacy exist. We aimed to investigate the anti-propulsive and central nervous system (CNS) effects of opium tincture in patients with chronic diarrhea. Materials and methods The study was a randomized, double-blinded, placebo-controlled, cross-over trial in subjects with chronic diarrhea refractory to standard treatment. Participants received opium tincture or placebo during two intervention periods, each lasting seven days. Bowel movements were recorded daily, and gastrointestinal transit time was investigated with the wireless motility capsule system. Gastrointestinal symptoms, health-related quality of life, and CNS effects (pupil size, reaction time, memory, and general cognition) were also investigated, along with signs of addiction. Results Eleven subjects (mean age: 45 ± 17 years, 46% males) with a median of 4.7 daily bowel movements were included. The number of daily bowel movements was reduced during opium tincture treatment to 2.3 (p = 0.045), but not placebo (3.0, p = 0.09). Opium tincture prolonged the colonic transit time compared to placebo (17 h vs. 12 h, p < 0.001). In both treatment arms, there were no changes in self-reported gastrointestinal symptoms, health-related quality of life, or CNS effects, and no indication of addiction was present. Conclusion Opium tincture induced anti-propulsive effects in patients with chronic diarrhea refractory to standard treatment. This indicates that opium tincture is a relevant treatment strategy for selected patients with chronic diarrhea. Moreover, no evidence of opioid-induced sedation or addiction was found. Trial Registration Number: NCT05690321 (registered 2023-01-10)

Trustworthiness judgments and pupil-size in individuals with schizophrenia

Individuals with schizophrenia show aberrant processing of social cues. In the current study, we (1) compared trustworthiness ratings of faces between patients with schizophrenia and healthy controls, (2) compared pupillary reactivity between patients and controls (3) examined whether trustworthiness judgments in schizophrenia are related to pupil reactivity, (4) and examined associations between trustworthiness judgements and symptom severity, specifically paranoia. Patients with schizophrenia spectrum disorders (N = 48) and healthy controls (N = 33) completed a Trustworthiness Task, during which their pupil size was measured via an eye-tracking device. The mean baseline-corrected pupil size was calculated from 24 pictures of real neutral faces, each presented for 2500 ms. Self-reported psychotic experiences were measured by Community Assessment of Psychic Functioning (CAPE–42), and symptom severity was rated by Brief Psychiatric Rating Scale (BPRS). No group differences were found in trustworthiness ratings or pupil reactivity parameters during trustworthiness judgments. Separately, among patients, absolute difference in pupil-size change and dilation after reaching minimum size were related to more severe positive symptoms and self-reported paranoia. Our results did not show social cognitive biases in the stable outpatients with schizophrenia, or the role of pupil reactivity in trustworthiness judgments. Future studies should use longer stimuli for pupillary reactivity and control the type and dosage of utilized antipsychotic medication. Further studies are required to explore relationships in larger and more symptomatic groups of patients.

Pain-induced effects on the pupillary light response under high and low illumination conditions.

The present study investigated the impact of two different light intensities on the pain-modulated pupillary light response (PLR). Additionally, it aimed to demonstrate parasympathetic and sympathetic influences on PLR parameters in response to pain, as predicted by functional models. A total of 24 participants were included in a randomized, repeated-measures design. The PLR was measured in response to both dark and bright light stimuli within two test cycles. Pain was induced using the cold pressor test (CPT), which involved immersing participants' feet in ice water. PLR measurements were taken during baseline and ice-water immersion within each test cycle. The assessed PLR parameters included initial diameter (INIT), latency (LAT), amplitude (AMP), and re-dilation time (ReDIL25). Along with these parameters, heart rate (HR) and pain ratings were also computed and analyzed. The CPT caused moderate pain in participants, and the resulting PLR parameters were found to be congruent with the expected parasympathetic and sympathetic nervous system activities. Although the luminance of the stimulus did influence PLR parameters, no interaction with pain exposure was found. The results showed that different aspects of pain experienced by an individual, as modulated through the sympathetic and parasympathetic nervous systems, are visible in their pupillary reactions to light. Notably, within the range used in the current study, light intensity did not significantly affect the pain-related PLR effects.

Single-centre real-life observational study on mortality and outcomes: decompressive craniectomy and brain death in traumatic brain injury, haemorrhage, and other cerebral diseases

BackgroundDecompressive hemicraniectomy (DHC) is used after severe brain damages with elevated, refractory intracranial pressure (ICP). In a non age-restricted population, mortality rates and long-term outcomes following DHC are still unclear. This study’s objectives were to examine both, as well as to identify predictors of unfavourable outcomes.MethodsWe undertook a retrospective observational analysis of patients aged 18 years and older who underwent DHC at the University Hospital of Bonn between 2018 and 2020, due to traumatic brain injury (TBI), haemorrhage, tumours or infections. Patient outcomes were assessed by conducting telephone interviews, utilising questionnaires for modified Rankin Scale (mRS) and extended Glasgow Outcome scale (GOSE). We evaluated the health-related quality of life using the EuroQol (EQ-5D-5L) scale.ResultsA total of 144 patients with a median age of 58.5 years (range: 18 to 85 years) were evaluated. The mortality rate was 67%, with patients passing away at a median of 6.0 days (IQR [1.9–37.6]) after DHC. Favourable outcomes, as assessed by the mRS and GOSE were observed in 10.4% and 6.3% of patients, respectively. Cox regression analysis revealed a 2.0% increase in the mortality risk for every year of age (HR = 1.017; 95% CI [1.01–1.03]; p = 0.004). Uni- and bilateral fixed pupils were associated with a 1.72 (95% CI [1.03–2.87]; p = 0.037) and 3.97 (95% CI [2.44–6.46]; p < 0.001) times higher mortality risk, respectively. ROC-analysis demonstrated that age and pupillary reactivity predicted 6-month mortality with an AUC of 0.77 (95% CI [0.69–0.84]). The only parameter significantly associated with a better quality of life was younger age.ConclusionsFollowing DHC, mortality remains substantial, and favourable outcomes occur rarely. Particularly in elderly patients and in the presence of clinical signs of herniation, mortality rates are notably elevated. Hence, the indication for DHC should be set critically.

Modelling of the early stage of retinal neurodegeneration via a topical injection of dopaminergic neurotoxin

Purpose: to develop a model of the early stage of retinal neurodegeneration via an intravitreal injection of the dopaminergic neurotoxin. Material and methods. The experiment was carried out on 20 Chinchilla rabbits. The experimental groups received intravitreal injection of 0.1 ml of 6-hydroxydopamine (6-OHDA) in NaCl 0.9 % with 0.5 % ascorbate, containing 0.25 or 0.5 mg 6-OHDA. The control group received injections of 0.1 ml of NaCl-ascorbate solution without neurotoxin. On the 7th and the 14th days after the injection, intraocular pressure (IOP), pupillary light reaction and ocular blood flow were estimated and the fundus was examined. On the 7th day after an injection of 0.25 mg 6-OHDA, we used ELISA to measure dopamine concentration in retinal homogenates, while on the 14th day after an injection of 0.5 mg 6-OHDA, the concentrations of dopamine, norepinephrine, TNF-a and endothelin-1 were measured by the same method. Results. On the 7th day after a 0,25 mg injection of neurotoxine, we revealed a decrease of dopamine in the retina (0.043 ± 0.130 pg/mg protein compared with 0.10 ± 0,03 pg/mg protein in the controls, р &lt; 0.01). On the 14th day, dopamine and norepinephrine levels showed a fourfold increase (р &lt; 0.05). An injection of 0.5 mg of 6-OHDA caused a threefold increase of dopamine (р &lt; 0.05) and a fivefold increase of norepinephrine (р &lt; 0.01) concentration in comparison with the controls. On the 14th day, endotheline-1 level was 65 % higher than in the controls after a 0.25 mg 6-OHDA injection (р &lt; 0.01) and 45 % higher after a 0,5 mg injection (р&lt;0.05). At the same time, TNF-α levels increased by 43 % (р &lt; 0.05) and 20 % (р &lt; 0.05) respectively. We also revealed a dose-dependent change of IOP, a disturbance of pupillary light reaction and decreased ocular blood flow after an injection of neurotoxin. Conclusion. A single intravitreal injection of dopaminergic neurotoxin 6-OHDA in the amount of 0.25 or 0.5 mg per eye leads to a neuroinflammation and vascular disorders, which are the main pathogenetic pathways of neurodegeneration. To model its early phase, the 0.25 mg dose is preferable as it causes less dramatic functional disorders. The latter model can be useful for the investigation of retinal neurodegeneration pathogenesis, the search for early diagnostic and prognostic markers thereof and the estimation of therapy effectiveness.

Saccades, pupil response and blink abnormalities in Huntington’s disease patients during free viewing

ObjectiveVideo-based eye tracking was used to investigate saccade, pupil, and blink abnormalities among patients with Huntington’s disease (HD) who watched sequences of short videos. HD, an autosomal dominant neurodegenerative disorder resulting from a CAG mutation on chromosome 4, produces motor and cognitive impairments including slow or irregular eye movements, which have been studied using structured tasks. MethodsTo explore how HD affects eye movements under instruction free conditions, we assessed 22 HD patients and their age matched controls in a 10-minute video-based free viewing task. ResultsPatients with HD experienced a significant reduction in saccade exploration rate following video clip transitions, an increase in pupil reactions to luminance changes after clip transitions, and a significant higher blink rate throughout the task compared to the control group. ConclusionsThese results show that HD has a significant impact on how patients visually explore and respond to their environment under unconstrained and ecologically natural conditions. SignificanceEye tracking in HD patients revealed saccadic, pupil, and blink abnormalities in early HD patients, suggestive of brain circuitry abnormalities that probably involve brain stem deficits. Further research should explore the impact of these changes on the quality of life of the patients affected by the disease.

Anisocoria After Direct Light Stimulus is Associated with Poor Outcomes Following Acute Brain Injury.

Assessing pupil size and reactivity is the standard of care in neurocritically ill patients. Anisocoria observed in critically ill patients often prompts further investigation and treatment. This study explores anisocoria at rest and after light stimulus determined using quantitative pupillometry as a predictor of discharge modified Rankin Scale (mRS) scores. This analysis includes data from an international registry and includes patients with paired (left and right eye) quantitative pupillometry readings linked to discharge mRS scores. Anisocoria was defined as the absolute difference in pupil size using three common cut points (> 0.5mm, > 1mm, and > 2mm). Nonparametric models were constructed to explore patient outcome using three predictors: the presence of anisocoria at rest (in ambient light); the presence of anisocoria after light stimulus; and persistent anisocoria (present both at rest and after light). The primary outcome was discharge mRS score associated with the presence of anisocoria at rest versus after light stimulus using the three commonly defined cut points. This analysis included 152,905 paired observationsfrom 6,654 patients witha mean age of 57.0 (standard deviation 17.9) years, and a median hospital stay of 5 (interquartile range 3-12) days. The mean admission Glasgow Coma Scale score was 12.7 (standard deviation 3.5), and the median discharge mRS score was 2 (interquartile range 0-4). The ranges for absolute differences in pupil diameters were 0-5.76mm at rest and 0-6.84mm after light. Using an anisocoria cut point of > 0.5mm, patients with anisocoria after light had worse median mRS scores (2 [interquartile range 0-4]) than patients with anisocoria at rest (1 [interquartile range 0-3]; P < .0001). Patients with persistent anisocoria had worse median mRS scores (3 [interquartile range 1-4]) than those without persistent anisocoria (1 [interquartile range 0-3]; P < .0001). Similar findings were observed using a cut point for anisocoria of > 1mm and > 2mm. Anisocoria after light is a new biomarker that portends worse outcome than anisocoria at rest. After further validation, anisocoria after light should be considered for inclusion as a reported and trended assessment value.

Review Article: Understanding Influenza-Related Eye Diseases

Eye flu also known as a conjuctivities or red eye is highly contagious disease as well as pink eye is among the most common disease world wild . The prominent system vission. The eye flu which can spread from one person to anotherr person. Opthalmology clinics around the world see a lot of patients with conjuctivities viral conjuctivities followed by bacterial conjuctivies is the most common cause of infection eye flu while allergic and toxin –induced eye flu are among the most common non - infection etiologics . One of the most typical causes of red eyes,conjuctivities strickes people of all ages and sociocconomic background.the majority of infection conjuctivities causes,upto 75% of them are caused by viral conjuctivities.this overviews briefly describe current literature findings ophthalmology related to corunavirus disease that become a worldwide pandemic. Virous account for 80% of all cases of acute cunjunctivities and adenoviruses ; entrovirus and herpes virus are the common causative agent in general , viral conjuctivities spreads easily .Opthalmology clinics around the world see a lot of patient with conjuctivities . severe pain , impaired vision and a painful pupillary reaction are red flags for more serious intraocular disorders that should be taken into account while treating suspected cases of conjunctivitis. Conjunctivitis in children is very contagious ,and if hygiene condition are not observed or treated carelessly,it is easily transferred to a heathly eye or from person to person . bacteria and viruses a head the list of organisms capable of invading the exposed cunjunctiva.