Cognitive Sequelae Research Articles

Neonatal care and developmental outcomes following preterm birth: A systematic review and meta-analysis.

Major amendments in neonatal care have been introduced in recent decades. It is important to understand whether these amendments improved the cognitive sequelae of preterm children. Through a large-scale meta-analysis, we explored the association between prematurity-related complications, neonatal care quality, and cognitive development from birth until 7 years. MEDLINE, APA PsycInfo, and EBSCO were searched. Peer-reviewed studies published between 1970 and 2022 using standardized tests were included. We evaluated differences between preterm and full-term children in focal developmental domains using random-effects meta-analyses. We analyzed data from 161 studies involving 39,799 children. Preterm birth was associated with inferior outcomes in global cognitive development (standardized mean difference = -0.57, 95% CI [-0.63, -0.52]), as well as in language/communication, visuospatial, and motor performance, reflecting mean decreases of approximately 7.3 to 9.3 developmental/intelligence quotients. Extreme prematurity, neonatal pulmonary morbidities, and older assessment age in very-to-extreme preterm cohorts were associated with worse outcomes. Contemporary neonatal medical and developmental care were associated with transient improvements in global cognitive development, evident until 2 to 3 years of age but not after. Blinding of examiners to participants' gestational background was associated with poorer outcomes in preterm cohorts, suggesting the possibility of a "compassion bias." The results suggest that preterm birth remains associated with poorer cognitive development in early childhood, especially following pulmonary diseases and very-to-extreme preterm delivery. Importantly, deficits become more pervasive with age, but only after births before 32 gestational weeks and not in moderate-to-late preterm cohorts. Care advancements show promising signs of promoting resiliency in the early years but need further refinements throughout childhood. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Long-term neurocognitive follow-up in children with traumatic brain injury: A literature review and monocentric cohort study

Children with mild traumatic brain injury (mTBI) may experience long-term cognitive sequelae. However, previous study results have been controversial. It remains unclear whether clinical follow-up is useful, how long patients should be followed-up, and which psychological dimensions should be investigated. Herein, we described neurocognitive evolution in a small sample of Italian children who were hospitalized for mTBI and systematically reviewed the existing evidence in this setting. In total, 15 children aged 4 – 16 (median, 9) years who were evaluated for mTBI at our institution between March 2017 and September 2018 were retrospectively enrolled. All patients underwent computed tomography or magnetic resonance imaging for clinical reasons; moreover, they underwent neurocognitive evaluation within few days from the event (T0), after 3 – 6 months (T1), and after 18 – 24 months (T2). Neuropsychological assessment included the Child Behavior Checklist, Developmental Neuropsychology Assessment II Edition, and Wechsler Intelligence Scale for Children. An electronic search was conducted to identify studies published in the past 12 years. Neurocognitive assessments revealed low scores in memory, sensorimotor, and social perception tasks at T1 and T2. Univariate analysis of neuroradiological and clinical findings revealed no risk factors for cognitive deficits. Overall, 17 studies involving 1336 children were reviewed and analyzed. Following mTBI, psychiatric disorders were frequently newly diagnosed and were associated with significant deficits in adaptive functioning and other pre-injury psychosocial risk factors. Our study findings demonstrate that children with mTBI exhibit subtle persistent cognitive difficulties that may affect academic and social functioning. Thus, follow-up using extensive neuropsychological evaluation is essential.

Rehabilitation and functional outcomes of COVID-19 patients in a rehabilitation hospital in Qatar.

Patients recovering from severe COVID-19 infections have experienced prolonged cognitive, physical, and psychological sequelae, including cardiorespiratory and motor deconditioning, neurological deterioration, anxiety, and depression. The impact of rehabilitation post-acute COVID-19 infection was recognized in the literature, but studies assessing and quantifying specific functional outcomes were lacking. This study aims to describe the characteristics and quantify the changes in functional outcomes of patients admitted to Qatar Rehabilitation Institute (QRI) for inpatient rehabilitation (IPR) post-COVID-19 infection during a 10-month period in 2021. This is a retrospective observational cohort study, which included individuals over 18 years of age with a documented COVID-19-positive diagnosis who were admitted to QRI for IPR due to COVID-19 complications. Data was collected by the investigators from January 1, 2021, until October 30, 2021. A total of 243 patients were included in this study. The changes in functional rehabilitation outcomes were assessed and quantified at both the patient's baseline (on admission to QRI) and after completion of IPR (on discharge). The duration of the IPR program varied based on each patient's baseline assessment. Patients were given a total of 8-12 weeks to achieve their rehabilitation goals and were discharged once those goals were met. Several validated tools were utilized in this study including Functional Independence Measure (FIM), Berg Balance Scale (BBS), Dynamic Gait Index (DGI), Modified Medical Research Council (mMRC) Dyspnea Scale, Mini-Mental State Examination (MMSE), and Right- and left-Hand Grip Strength. In addition, patients' diet, the need for respiratory support, and the presence of a tracheostomy tube before and after IPR were also recorded. In total, 84.4% of the included patients were males (n = 205); with a mean age of 52.44 ± 12.99 years. The most commonly reported comorbidities were type 2 diabetes (62.1%) and hypertension (49.8%) with 83.5% of patients experiencing critical illness neuromyopathy. The average patients' length of stay in QRI was 33.92 ± 27.72 days. A statistically significant improvement in all functional outcome scales was noted following the completion of the IPR program (p = 0.001). The number of patients requiring modification to their diet or feeding via nasogastric tube (NGT) significantly decreased by 35% and 93%, respectively (p = 0.001). Patients requiring respiratory support decreased by 98% (p = 0.001) and the need for a tracheostomy tube among patients was reduced by 95% (p = 0.001). IPR following COVID-19 infection was associated with significant functional, motor, and cardiorespiratory improvement. Dedicating clinics for post-COVID-19 rehabilitation would ensure improved patient outcomes and enhanced recovery.

Early region-specific impact of adjuvant radiation therapy on cognition and quality of life in adult patients with primary brain tumors.

While treatments for primary brain tumors increase survival, they have cognitive sequelae. Neurocognition's anatomical distribution makes it susceptible to brain damage. This study aims to evaluate the contribution of radiotherapy on short-term cognitive impairment. Using a prospective database of cognitive rehabilitation in adults operated on for primary brain tumors, a retrospective sub-analysis of the contribution of radiotherapy was performed. Thirty-four subdivisions of 12 neurocognitive regions were delineated in 48 irradiated patients and 30 non-irradiated patients. In the first group, the correlation between radiation dose and deterioration was evaluated. In all patients, the impact of tumor and surgical changes on dysfunction was calculated and compared with dose-dependent response. The correlation between cognitive status and radiation dose is especially strong and significant in the left hemisphere and in specific subdivisions such as the posterior hippocampus or the dorsolateral prefrontal cortex, with the left prevailing over posterior dominance. Memory is the most affected domain 1month after radiotherapy, as attention is three months later. The hippocampus is involved in various cognitive domains in addition to memory. The prefrontal subregions and the genu of the corpus callosum are more affected by the relationship with disease and surgical changes than by radiation exposure. Patients ongoing a course of radiotherapy do not benefit from concurrent cognitive rehabilitation. There is a correlation between the dose of radiation received by several encephalic regions and degree of short-term domain-specific cognition decline, considering other factors of risk and cognitive rehabilitation.

Assessment of Motor Imagery and Its Relationship to Functional Impairment in Post-Stroke Patients: A Descriptive Cross-Sectional Study.

Background: Motor and cognitive sequelae are common in patients who have experienced a stroke. Recent advances in neuroscience have enabled the development of novel therapeutic approaches, such as motor imagery, which facilitate motor learning. The objective of this study is to examine the relationship between implicit and explicit motor imagery abilities and their correlation with functional impairment in post-stroke patients. Methods: A descriptive cross-sectional study was conducted with 36 patients who had experienced a stroke between March 2008 and March 2023. The capacity to generate both implicit and explicit motor imagery and to perform physical functions was evaluated. The relationship between implicit and explicit motor imagery measures was investigated using Pearson's correlation coefficient. The factorial structure, which encompasses the capacity to generate motor imagery, whether implicit or explicit, and physical function, was subjected to analysis. Results: A correlation was identified between the time taken to identify images and the accuracy of this process, with the right hand (R = 0.474), the left hand (R = 0.568), and the left foot (R = 0.344) all demonstrating significant associations. Additionally, a notable correlation was observed between the two subscales of the KVIQ-10 scale (R = 0.749). No association was identified between the capacity to generate implicit and explicit motor imagery. Two- and three-factor solutions were obtained for the right and left hemibodies, respectively. On both sides, accuracy in identifying images and physical function constituted a single factor, while time to generate images for both hands and feet constituted a second factor. Conclusions: In conclusion, no significant data were reported regarding the association between the capacity to generate implicit and explicit motor imagery in the studied sample. However, the ability to generate implicit motor imagery was related to physical function, suggesting that it may serve as a screening criterion for implementing specific therapeutic approaches in post-stroke patients.

Role of Transforming Growth Factor-β in Pathogenesis of Pulmonary Fibrosis in COVID-19, Post-COVID Syndrome, Oncological and Chronic Inflammatory Lung Diseases

INTRODUCTION: Persistent post-COVID syndrome is the persistent physical, medical and cognitive sequelae of coronavirus disease 2019 (COVID-19), including persistent immunosuppression, pulmonary, cardiac and vascular fibrosis which lead to increased mortality and impair the quality of life of patients. АIM: To analyze the completed foreign and domestic studies on the pathophysiology of transforming growth factor-β (TGF-β) in conditions of COVID-19, post-COVID syndrome, oncological and chronic inflammatory lung diseases. Mast cells are among the main producers of inflammatory cytokines in COVID-19, their stimulation leads to the release of many proinflammatory cytokines, such as interleukin 1β, tumor necrosis factor α, interleukin 6, and also TGF-β. The basis of the pathogenesis of post-COVID syndrome is the overexpression of TGF-β leading to a prolonged state of immunosuppression and fibrosis. TGF-β acts as a tumor suppressor inhibiting proliferation and inducing apoptosis in the early stages of oncogenesis; plays an important role in most cellular biological processes leading to remodeling of the airway structures; is involved in epithelial changes, in subepithelial fibrosis, remodeling of smooth muscle of airways and in microvascular changes; induces resistance to glucocorticosteroids; stimulates the production of blood coagulation factor XII, thereby leading to development of potentially fatal complications, such as pulmonary embolism and ischemic stroke. CONCLUSION: In this literature review, a structured analysis of a multicomponent role of TGF-β in the pathogenesis of post-COVID syndrome, pulmonary fibrosis in COVID-19, tumors of respiratory system, chronic obstructive pulmonary disease, bronchial asthma, is given. A possible use of TGF-β as a biomarker of severe and moderate degree of COVID-19 is substantiated.

Slow-Paced Breathing Intervention in Healthcare Workers Affected by Long COVID: Effects on Systemic and Dysfunctional Breathing Symptoms, Manual Dexterity and HRV.

Many COVID-19 survivors still experience long-term effects of an acute infection, most often characterised by neurological, cognitive and psychiatric sequelae. The treatment of this condition is challenging, and many hypotheses have been proposed. Non-invasive vagus nerve stimulation using slow-paced breathing (SPB) could stimulate both central nervous system areas and parasympathetic autonomic pathways, leading to neuromodulation and a reduction in inflammation. The aim of the present study was to evaluate physical, cognitive, emotional symptoms, executive functions and autonomic cardiac modulation after one month of at-home slow breathing intervention. 6655 healthcare workers (HCWs) were contacted via a company email in November 2022, of which N = 58 HCWs were enrolled as long COVID (cases) and N = 53 HCWs as controls. A baseline comparison of the two groups was performed. Subsequently each case was instructed on how to perform a resonant SPB using visual heart rate variability (HRV) biofeedback. They were then given a mobile video tutorial breathing protocol and asked to perform it three times a day (morning, early afternoon and before sleep). N = 33 cases completed the FU. At T0 and T1, each subject underwent COVID-related, psychosomatic and dysfunctional breathing questionnaires coupled with heart rate variability and manual dexterity assessments. After one month of home intervention, an overall improvement in long-COVID symptoms was observed: confusion/cognitive impairment, chest pain, asthenia, headache and dizziness decreased significantly, while only a small increase in manual dexterity was found, and no relevant changes in cardiac parasympathetic modulation were observed.

Oneyear longitudinal study on biomarkers of blood–brain barrier permeability in COVID-19 patients

The pathophysiology behind neurological and cognitive sequelae of COVID-19 may be related to dysfunction of the blood-brain barrier (BBB) and previous research indicate transient neuronal injury and glial activation. The aim of this study was to investigate if COVID-19 is related to increased BBB permeability by analyzing leakage of biomarkers such as astrocyte-derived extracellular vesicles (EVs) and S100B. We also investigated whether levels of these biomarkers correlated with self-reported symptoms that persisted > 2 months. The samples in this 1-year follow-up study came from an ongoing longitudinal study of unvaccinated patients hospitalized for COVID-19 at Danderyd University Hospital, Stockholm, Sweden, between April and June 2020. Blood samples were collected at baseline and 4, 8, and 12 months after hospitalization. Information on self-reported clinical symptoms was collected at follow-up visits. A total of 102 patients were enrolled, and 47 completed all follow-up measurements. Peak levels of both biomarkers were observed at 4 months in the subset of 55 patients who were measured at this timepoint. At 12 months, the biomarkers had returned to baseline levels. The biomarkers were not correlated with any of the long-term self-reported symptoms. COVID-19 is associated with transient increased BBB permeability, shown by elevated levels of astrocyte biomarkers in plasma. However, these levels return to baseline 12 months post-infection and do not correlate with long-term symptoms. Further research is needed to unravel the underlying mechanisms causing long-term symptoms in COVID-19 patients.

Deep into Cognition: The Neuropsychological Identikit of Younger and Older Individuals after COVID-19 Infection.

The literature on COVID-19 continues to increase daily. Cognitive sequelae associated with COVID-19 infection still draw the attention of the scientific community given the lack of consensus about their existence, etiology, characterization and reversibility. The aim of this study is to provide a neuropsychological identikit for younger (<65 years) and older (≥65 years) individuals diagnosed with COVID-19 infection, at baseline and after 3 and 6 months. In total, 226 individuals took part in a retrospective observational study and their cognitive performance was compared across groups (younger adults vs. older adults) and time (T0, T1, T2). The results highlighted differences between younger and older adults in the Montreal Cognitive Assessment (MoCA) global score, as expected in consideration of the different physiological conditions of the two populations. However, memory performance highlighted the two groups as characterized by a difference in patterns of recall that may move beyond a physiological explanation and provide information about COVID-19 cognitive sequelae. This study suggests that cognitive deficits observed in COVID-19 survivors may reflect a difficulty in attention and concentration that interferes mainly with retrieval processes. This result fits well with the concept of "brain fog" typical of post-COVID-19 syndrome and may also reflect the stress experienced while facing the pandemic.

B - 105 ICANS, CAR-T, and Cognition: a Case Study

Abstract Objective Immune effector cell-associated neurotoxicity syndrome (ICANS), an autoimmune delirious condition, affects 37.5% to 77% of individuals during or after chimeric antigen receptor T-cell (CAR-T) treatment for hematologic cancers (Grant et al., 2022). Initial clinical response varies widely but may include apraxia, aphasia, disorientation, and hallucinations (Möhn et al., 2022). Recent research indicates complete symptom resolution in most patients a month post-ICANS onset (Sales et al., 2023). However, a self-report study suggested more than 1 in 3 report persisting cognitive sequelae 1–5 years post-ICANS onset (Rurak et al., 2020). This discrepancy may be due to subtle changes missed by the Montreal Cognitive Objective Assessment (Sales et al., 2023; Möhn et al., 2022). The current case report investigates neurobehavioral outcome post-ICANS via comprehensive neuropsychological assessment. Method Two weeks post-CAR-T therapy, a 53-year-old male exhibited abrupt onset facial palsy and cognitive slowing prompting hospitalization. His wife reported new-onset apathy, atypical behaviors exacerbation (e.g., licking plate), and cognitive lapses (e.g., short-term memory, slowing, repeating questions) with little insight. Neuroimaging revealed supratentorial white matter hyperintensities plus calvarium and R skull base enhancing lesion regression. Results Neuropsychological assessment 10-months post-ICANS revealed subtle executive inefficiencies with family reports of improved yet ongoing social disinhibition and apathy. Conclusions This is the first comprehensive neuropsychological assessment of a patient who developed ICANS post-CAR-T therapy. Neuropsychologists should be aware of delayed cognitive sequelae possibility of this advancing treatment option. Future studies will be useful for patient/family preparation.

Two profiles of post-stroke drivers based on their driving perception

ObjectiveStroke is the leading cause of acquired disability in adults, and can induce different sequelae which impact on abilities such as driving. This study investigated how post-stroke patients perceived their driving practice and behavior. The aim of this study was to determine different profiles of post-stroke drivers according to their driving perception. MethodsAmong 86 post-stroke patients who had undergone an official fitness-to-drive assessment in 2019 in the Kerpape Center or the Henry Gabrielle Hospital (France), 69 returned to drive. These 69 participants completed a questionnaire about their socio-demographic and clinical characteristics, and driving perception, approximately three years after resuming driving. Questions about driving perception were statistically analyzed using hierarchical clustering analysis. Socio-demographic, driving, and clinical characteristics from the clusters obtained were then compared. ResultsClustering analysis revealed two profiles of post-stroke drivers. One group consisting of 2/3 of the participants reported modified driving behavior, while the other group perceived no driving changes. A higher proportion of participants from the modified driving group reported driving significantly less, experiencing less pleasure, increased tiredness and more fear when driving post-stroke than those from the unmodified driving group. They also stated that they experienced more difficulties, avoided more situations, and implemented more driving strategies than participants in the unmodified driving group. Participants in the modified driving group were also younger (p = 0.014), lived in more rural areas (p = 0.028), and had more sequelae, including fatigue (p = 0.002), motor sequelae (p = 0.035), and cognitive sequelae (p = 0.013) than participants who did not modify their driving. ConclusionsTwo profiles of post-stroke drivers were identified: those who had perceived the need to modify their driving behavior, and those who had perceived no driving changes. Differences in socio-demographic characteristics may partly explained the divergencies between the two groups. Other factors such as self-awareness of driving abilities may influence their driving perception. Two lines of action could be investigated to enable post-stroke drivers to better appreciate their driving abilities. The first would be to develop targeted support programs to help drivers become more aware of their own abilities, for example using video support during on-road training to replay critical situations and improve awareness of their own abilities. A second approach would be to deploy technological driving assistance systems. A monitoring system enabling the driver to adjust his driving in real time could be very useful and relevant to develop.

Neuropsychological outcomes of patients with haematological malignancies undergoing chimeric antigen receptor T-cell therapy: protocol for a prospective study

IntroductionImmune effector cell-associated neurotoxicity syndrome (ICANS) is a common side-effect of chimeric antigen receptor T-cell (CAR-T) therapy, with symptoms ranging from mild to occasionally life-threatening. The neurological, cognitive, psychiatric and...

Medium- and Long-Term Effects of COVID-19 in a Population of Patients Admitted to the Intensive Care Unit: Cognitive and Psychological Sequelae and Quality of Life Six Months and One Year after Discharge.

Most researchers have assessed cognitive functions in post-COVID-19 patients by means of screening tools and found cognitive sequelae in addition to anxiety, stress, depression, and a reduced quality of life (QoL). This study was aimed at investigating cognitive and psychological sequelae in patients admitted to the intensive care unit (ICU) six months (t6) and one year (t12) after discharge from the hospital, the impact of critical illness on well-being and QoL, and the protective role of cognitive reserve (CR). Twenty-three ICU patients underwent an extensive neuropsychological test battery at t6 and t12; a healthy control group underwent the same evaluation. Patient scores were compared with control scores: patients reported significantly lower scores in visual-spatial functions, both at t6 (U = 122; p = 0.033) and at t12 (U = 70; p = 0.003), and higher levels of anxiety (U = 126; p = 0.043) and depression (U = 97; p = 0.005) at t6; the levels of anxiety decreased at t12, while only depression symptoms persisted (U = 99.5; p = 0.025). Regarding the QoL, patients obtained lower scores in the physical component of QoL, both at t6 (U = 72; p = 0.008) and at t12 (U = 56.5; p = 0.005). Few and moderate correlations emerged between isolated cognitive functions and CR and the length of hospital stay. The results suggest a prevalent visual-spatial involvement, the medium- and long-term persistence of psychological sequelae, and a reduced QoL in ICU patients.

Long COVID Brain Fog Treatment: Findings from a Pilot Randomized Controlled Trial of Constraint-Induced Cognitive Therapy.

Long COVID brain fog is often disabling. Yet, no empirically-supported treatments exist. This study's objectives were to evaluate feasibility and efficacy, provisionally, of a new rehabilitation approach, Constraint-Induced Cognitive Therapy (CICT), for post-COVID-19 cognitive sequelae. Sixteen community-residents ≥ 3-months post-COVID-19 infection with mild cognitive impairment and dysfunction in instrumental activities of daily living (IADL) were enrolled. Participants were randomized to Immediate-CICT or treatment-as-usual (TAU) with crossover to CICT. CICT combined behavior change techniques modified from Constraint-Induced Movement Therapy with Speed of Processing Training, a computerized cognitive-training program. CICT was deemed feasible if (a) ≥80% of participants completed treatment, (b) the same found treatment highly satisfying and at most moderately difficult, and (c) <2 study-related, serious adverse-events occurred. The primary outcome was IADL performance in daily life (Canadian Occupational Performance Measure). Employment status and brain fog (Mental Clutter Scale) were also assessed. Fourteen completed Immediate-CICT (n=7) or TAU (n=7); two withdrew from TAU before their second testing session. Completers were [M (SD)]: 10 (7) months post-COVID; 51 (13) years old; 10 females, 4 males; 1 African American, 13 European American. All the feasibility benchmarks were met. Immediate-CICT, relative to TAU, produced very large improvements in IADL performance (M=3.7 points, p<.001, d=2.6) and brain fog (M=-4 points, p<.001, d=-2.9). Four of five non-retired Immediate-CICT participants returned-to-work post-treatment; no TAU participants did, p=.048. CICT has promise for reducing brain fog, improving IADL, and promoting returning-to-work in adults with Long COVID. Findings warrant a large-scale RCT with an active-comparison group.

Electroencephalogram-Based Anesthesia Indices Differently React to Modulations of Alpha-Oscillatory Activity.

The electroencephalographic (EEG) provides the anesthesiologist with information regarding the level of anesthesia. Processed EEG indices are available that reflect the level of anesthesia as a single number. Strong oscillatory EEG activity in the alpha-band may be associated with an adequate level of anesthesia and a lower incidence of cognitive sequelae. So far, we do not know how the processed indices would react to changes in the alpha-band activity. Hence, we modulated the alpha-oscillatory activity of intraoperative EEG to assess possible index changes. We performed our analyses based on data from 2 studies. Intraoperative EEG was extracted, and we isolated the alpha-band activity by band-pass filtering (8-12 Hz). We added or subtracted this activity to the original EEG in different steps with different amplifications of the alpha signal. We then replayed these signals to the bispectral index (BIS), the Entropy Module (state entropy [SE]), the CONOX (qCON), and the SEDLine (patient state index [PSI]); and evaluated the alpha-band modulation's impact on the respective index. The indices behaved differently to the modulation. In general, indices decreased with stronger alpha-band activity, but the rate of change was different with SE showing the strongest change (9% per step) and PSI and BIS (<5% per step) showing the weakest change. A simple regression analysis revealed a decrease of 0.02 to 0.09 index points with increasing alpha amplification. While the alpha-band in the intraoperative EEG seems to carry information regarding the quality of anesthesia, changes in the alpha-band activity do neither strongly nor uniformly influence processed EEG indices. Hence, to assess alpha-oscillatory activity's strength, the user needs to focus on the raw EEG or its spectral representation also displayed on the monitoring systems.

Recovery from Sepsis: Management beyond Acute Care.

Recovery from sepsis is a key global health issue, impacting 38 million sepsis survivors worldwide per year. Sepsis survivors face a wide range of physical, cognitive, and psychosocial sequelae. Readmissions to hospital following sepsis are an important driver of global healthcare utilization and cost. Family members of sepsis survivors also experience significant stressors related to their role as informal caregivers. Increasing recognition of the burdens of sepsis survivorship has led to the development of postsepsis recovery programs to better support survivors and their families, although optimal models of care remain uncertain. The goal of this article is to perform a narrative review of recovery from sepsis from the perspective of patients, families, and health systems.

CSF biomarkers of neurotoxicity in childhood cancer survivors after cranial radiotherapy or surgery.

Treatment of pediatric brain tumors is associated with potential long-term cognitive sequelae. Patients treated with craniospinal irradiation for posterior fossa tumors are at high risk. New biomarkers that could help to differentiate treatment effects from other causes of cognitive dysfunction would be valuable in tailoring optimal survivorship care. Biomarkers that reflect biological mechanisms behind treatment-associated cognitive decline would also be important in the evaluation of future treatment regimens for pediatric brain or skull base tumors. In this biomarker-finding study, 10 adult survivors of pediatric medulloblastoma, skull base tumors, and posterior fossa low-grade glioma underwent study specific lumbar puncture at a minimum of 17 years following treatment. We analyzed cerebrospinal fluid biomarkers reflecting neuron and astrocyte integrity, amyloid metabolism, inflammation, extracellular matrix, synaptic integrity, and blood-brain barrier function. The values were compared with biomarker levels in healthy controls of comparable age. Biomarkers reflecting neuronal injury (neurofilament light chain protein), astrocyte injury or activation (glial fibrillary acidic protein) as well as inflammation (YKL-40) were significantly elevated in cancer survivors compared to controls. Biomarkers reflecting amyloid metabolism showed a pattern of decrease in patients treated for medulloblastoma. The results suggest a potential chronic low-grade neurodegeneration and astrocyte activation in patients treated for pediatric brain or skull base tumors. Protein biomarkers of CNS disease could potentially be used to increase our understanding of the contribution from different tumor treatments with regard to long-term symptoms in cancer patients.

Meeting complex multidimensional needs in older patients and their families during and beyond critical illness.

To highlight the emerging crisis of critically ill elderly patients and review the unique burden of multidimensional morbidity faced by these patients and caregivers and potential interventions. Physical, psychological, and cognitive sequelae after critical illness are frequent, durable, and robust across the international ICU outcome literature. Elderly patients are more vulnerable to the multisystem sequelae of critical illness and its treatment and the resultant multidimensional morbidity may be profound, chronic, and significantly affect functional independence, transition to the community, and quality of life for patients and families. Recent data reinforce the importance of baseline functional status, health trajectory, and chronic illness as key determinants of long-term functional disability after ICU. These risks are even more pronounced in older patients. The current article is an overview of the outcomes of older survivors of critical illness, putative interventions to mitigate the long-term morbidity of patients, and the consequences for families and caregivers. A multimodal longitudinal approach designed to follow patients for one or more years may foster a better understanding of multidimensional morbidity faced by vulnerable older patients and families and provides a detailed understanding of recovery trajectories in this unique population to optimize outcome, goals of care directives, and ongoing informed consent to ICU treatment.

Predominance of Cephalic Presentation at Birth: An Oxygen Delivery-Based Concept

Background: Fetuses closer to term present predominantly as cephalic, and by the time of delivery 96-97% of them are born headfirst. To date, no coherent hypothesis has been put forth to explain the phenomenon. Observation: As pregnancy advances, there is a progressive increase in cephalic presentation; by 25 weeks, 60% are cephalic, at 35 weeks 90% cephalic and at term only less than 3-4% remain breech. Hypothesis: Oxygen delivery to the fetus comes from the environment through the parturient and it must traverse a very long passage to get to the fetal tissues making oxygen delivery a very precarious process. The fetus develops several compensatory mechanisms to enhance the delivery of oxygen—higher hemoglobin level, hemoglobin with greater affinity for oxygen, the double Bohr phenomenon to improve the diffusion of oxygen from the parturient and lastly redesign of the fetal circulation to increase flow to the brain whilst in the state of near chronic hypoxia whilst in utero. The better flow of blood to the head and therefore more oxygen to the brain makes this organ the densest causing it to progressively present cephalic as pregnancy advances. Implications: The hypothesis aligns well with not only the observed progressive cephalic phenomenon but also the long-term subtle cognitive deficits and neurological sequelae observed in several studies of those born breech. Conclusion: Cephalic presentation at birth is driven by better blood flow to the brain as another compensatory mechanism to cope with hypoxia.

Exploring Memory Systems After Pediatric Posterior Fossa Tumor: From Memory Profile Comparisons in Nonirradiated Versus Irradiated Patients to Episodic Memory Tests Capable of Detecting Radiation-induced Hippocampal Damage

AimsPediatric posterior fossa tumor (PFT) survivors experience long-term cognitive sequelae, including memory disorders, for which irradiation is one of the main risk factors. The aims of the present study were to (1) explore the profile of impairment in episodic, semantic, working and procedural memory systems in irradiated versus nonirradiated PFT survivors, and (2) test whether an autobiographical questionnaire and a two-phase ecological test (Epireal) assessing episodic memory are more sensitive to radiation-induced hippocampal damage than commonly used tests. Materials and methodsA total of 60 participants (22 irradiated PFT survivors, 17 nonirradiated PFT survivors, and 21 controls) were included in the prospective IMPALA study. They all underwent a broad battery of tests assessing the different memory systems in two 2-day sessions 3 weeks apart. We performed between-groups comparisons and analyzed impairment profiles, using -1.65 SDs as a cut-off. For irradiated patients, correlations were calculated between mean radiation doses to key brain structures involved in memory (hippocampus, cerebellum, and striatum) and corresponding memory scores. ResultsPBT survivors performed significantly more poorly than controls (p < 0.001) on conventional tests of episodic, semantic and working memory: 64% of irradiated patients and 35% of nonirradiated patients had a deficit in at least two memory systems, with episodic memory impairment being more specific to the irradiated group. Epireal had a larger effect size than the other episodic memory tests, allowing us to detect deficits in a further 18% of irradiated patients. These deficits were correlated with the mean radiation dose to the left hippocampus. ConclusionMemory impairment is a frequent long-term cognitive sequela in PFT survivors, especially after radiation therapy. New ecological tests of episodic memory that are more sensitive to radiation-induced deficits than conventional tests could yield specific markers of the toxicity of medial temporal lobe irradiation.