The Similarities and Differences Between Glomerular vs. Non-glomerular Diagnoses on Intelligence and Executive Functions in Pediatric Chronic Kidney Disease: A Brief Report

Pediatric chronic kidney disease (CKD) appears to be a heterogeneous group of conditions, but this heterogeneity has not been explored with respect to its impact on neurocognitive functioning. This study investigated the neurocognitive functioning of those with glomerular (G) vs. non-glomerular (NG) diagnoses. Data from the North American CKiD Study were employed and the current study included 1,003 children and adolescents with mild to moderate CKD. The G Group included 260 participants (median age = 14.7 years) and the NG Group included 743 individuals (median age = 9.0 years). Neurocognitive measures assessed IQ, inhibitory control, attention regulation, problem solving, working memory, and overall executive functioning. Data from all visits were included in the linear mixed model analyses. After adjusting for sociodemographic and CKD-related covariates, results indicated no differences between the diagnostic groups on measures of IQ, problem solving, working memory, and attention regulation. There was a trend for the G group to receive better parent ratings on their overall executive functions (p < 0.07), with a small effect size being present. Additionally, there was a significant G group X hypertension interaction (p < 0.003) for inhibitory control, indicating that those with both a G diagnosis and hypertension performed more poorly than the NG group with hypertension. These findings suggest that the separation of G vs. NG CKD produced minimal, but specific group differences were observed. Ongoing examination of the heterogeneity of pediatric CKD on neurocognition, perhaps at a different time point in disease progression or using a different model, appears warranted.

Reduced Intensity Hematopoietic Cell Transplantation Improves Cerebral Hemodynamics in Children with Sickle Cell Disease

Introduction Allogeneic hematopoietic cell transplantation (HCT) is increasingly being utilized in patients with sickle cell disease (SCD) to prevent progressive organ dysfunction, including for primary or secondary stroke prevention. However, outcomes after HCT have mostly been evaluated using broad measures such as overall survival and event free survival with limited direct physiologic evidence of improved cerebral hemodynamics. Cerebral blood flow (CBF; mL blood/100 g tissue/min) is increased in SCD to compensate for chronic anemia, reduced oxygen carrying capacity and to maintain adequate oxygen delivery to the brain tissue. In SCD patients, CBF is inversely associated with intelligence quotient (Strouse JJ, et al. Blood. 2006;108(1):379-381.) and working memory (Prussien KV, et al. Stroke. 2021;52(5):1830-1834.) and has been shown to improve with blood transfusions (Guilliams KP, et al. Blood. 2018;131(9):1012-1021.). Assessment of CBF may help predict long-term neurocognitive outcomes in patients with SCD and assess therapeutic responses to therapies. Additionally, the high metabolic demand of the brain potentially makes assessment of CBF a sensitive predictor of future multiorgan damage in patients with SCD and hence may be useful to help determine eligibility of patients for curative therapies. Methods We performed anatomical and hemodynamic magnetic resonance imaging (MRI) of the brain prior to, and at 6 months after HCT in children with SCD undergoing a reduced intensity conditioning based HCT on a clinical study (NCT04362293). All patients received pretransplant conditioning with hydroxyurea, azathioprine, alemtuzumab, thiotepa and low dose total body irradiation (200-400 cGy). All patients received an unmanipulated mobilized peripheral blood derived hematopoietic stem and progenitor cell graft. One patient who received the graft from a haploidentical (HAPLO) donor also received post-transplant cyclophosphamide. Graft versus host disease prophylaxis comprised of sirolimus. A 3-dimensional (3D) T1 sequence was used for gray/white matter segmentation. 3D-pulsed arterial spin labeling (ASL) perfusion imaging (3 mm isotropic) was acquired to measure resting CBF. Mean CBF values were calculated from gray matter. Mean ± standard deviation and median values for various variables are presented. Results Four consecutive patients had 2 serial MRIs performed (one before HCT and another 6 months after HCT). Median age at HCT was 14.5 years. Indications for HCT, donor type and whether patients were receiving chronic transfusion therapy (CTT) prior to HCT are indicated in the Table. No patient had prior evidence of overt stroke. All patients engrafted and had >99% donor myeloid chimerism at the time of the post-HCT imaging. Mean pre-HCT hemoglobin was 8.7 ± 0.8 g/dL (median 8.6 g/dL) and it increased to 12.5 ± 2.1 g/dL (median 12.4 g/dL) at 6 months after HCT. All patients exhibited elevated resting CBF values prior to HCT (123.8 ± 32.2 mL blood/100 g tissue/min, median 112.8 mL blood/100 g tissue/min), that decreased following HCT (71.1 ± 32.1 mL blood/100 g tissue/min, median 72.8 mL blood/100 g tissue/min) (Table and Figure). None of the patients had any clinical neurological complications or imaging evidence of new infarcts or anatomical abnormalities in the follow up period. Conclusion Our preliminary results indicate that it is feasible to quantify CBF in patients with SCD before and after HCT using MRI. We demonstrate that cerebral hemodynamics improve after HCT in children with SCD, indicated by a decrease in CBF to near normal values (normal CBF ~80 mL blood/100 g tissue/min). The more substantial changes (-50% and -78%) are seen in children who were not receiving CTT, suggesting that CTT might partially mitigate CBF elevation prior to HCT. Nevertheless, 2 patients receiving CTT prior to HCT also had a further modest decrease in CBF after HCT (-5% and -18%). We plan to follow these changes at serial time points annually after HCT and correlate them with changes in neurocognitive functioning and other functional MRI measures. Improved CBF is expected to reduce stroke risk and may also preserve or improve neurocognitive functioning, and prospective monitoring of these outcomes are underway. Data on all the study participants who have undergone an HCT and had 2 serial MRIs performed by the ASH annual meeting will be presented. Figure 1 Figure 1. Disclosures Sharma: Vertex Pharmaceuticals/CRISPR Therapeutics: Other: Salary support paid to institution; Medexus Inc: Consultancy; CRISPR Therapeutics: Other, Research Funding; Novartis: Other: Salary support paid to institution; Spotlight Therapeutics: Consultancy; Vindico Medical Education: Honoraria. Triplett: Miltenyi: Other: Travel, meeting registration. Hankins: Vindico Medical Education: Consultancy; UpToDate: Consultancy; Global Blood Therapeutics: Consultancy; Bluebird Bio: Consultancy.

The Impact of Neurocognitive Functioning on the Course of Posttraumatic Stress Symptoms following Civilian Traumatic Brain Injury

Background: One out of seven individuals who have suffered a traumatic brain injury (TBI) develops a posttraumatic stress disorder (PTSD), which is often associated with neurocognitive impairment. The present study explores the impact of neurocognitive functioning after mild, moderate, and severe TBI on the course of PTSD symptoms. Methods: The data of 671 adults admitted to hospital for a TBI was drawn from the Collaborative European Neurotrauma Effectiveness Research (CENTER-TBI) study. After six- and 12-months post-injury, participants completed the PTSD Checklist-5 (PCL-5), from which change scores were calculated. At six months, participants also completed a neurocognitive assessment including the Rey Auditory Verbal Learning Test, the Trail Making Test, and the Cambridge Neuropsychological Test Automated Battery (CANTAB). Linear regressions were performed to identify associations between cognitive functioning and PCL-5 change scores. Results: Overall, mean PCL-5 change scores showed no clear change (−0.20 ± 9.88), but 87 improved and 80 deteriorated by a change score of 10 or more. CANTAB Rapid Visual Information Processing scores were significantly associated with PCL-5 change scores. Conclusions: Strong sustained attention was associated with improvement in PTSD symptoms. Assessing cognitive performance may help identify individuals at risk of developing (persisting) PTSD post-TBI and offer opportunities for informing treatment strategies.

Neurocognitive, psychiatric, and substance use characteristics in a diverse sample of persons with OUD who are starting methadone or buprenorphine/naloxone in opioid treatment programs

Background Medications for opioid use disorder such as opioid agonist treatment (OAT, including methadone, buprenorphine) are the gold standard intervention for opioid use disorder (OUD). Persons with OUD have high rates of neurocognitive impairment and psychiatric and substance use disorders, but few studies have examined these characteristics in diverse patients initiating OAT in opioid treatment programs (OTPs). Additionally, in these individuals, poor neurocognitive functioning and psychiatric/other substance use disorders are associated with poor OUD treatment outcomes. Given rapid changes in the opioid epidemic, we sought to replicate findings from our pilot study by examining these characteristics in a large diverse sample of persons with OUD starting OTP-based OAT. Methods Ninety-seven adults with OUD (M age = 42.2 years [SD = 10.3]; M education = 11.4 years [SD = 2.3]; 27% female; 22% non-Hispanic white) were enrolled in a randomized longitudinal trial evaluating methadone versus buprenorphine/naloxone on neurocognitive functioning. All participants completed a comprehensive neurocognitive, psychiatric, and substance use evaluation within one week of initiating OAT. Results Most of the sample met criteria for learning (79%) or memory (69%) impairment. Half exhibited symptoms of current depression, and comorbid substance use was highly prevalent. Lifetime cannabis and cocaine use disorders were associated with better neurocognitive functioning, while depression was associated with worse neurocognitive functioning. Conclusions Learning and memory impairment are highly prevalent in persons with OUD starting treatment with either methadone or buprenorphine/naloxone in OTPs. Depression and comorbid substance use are prevalent among these individuals, but neither impact learning or memory. However, depression is associated with neurocognitive impairment in other domains. These findings might allow clinicians to help persons with OUD starting OAT to develop compensatory strategies for learning and memory, while providing adjunctive treatment for depression. Trial Registration NCT, NCT01733693. Registered November 4, 2012, https://clinicaltrials.gov/ct2/show/NCT01733693.

Long-term health-related quality of life and neurocognitive functioning after treatment in skull base meningioma patients

OBJECTIVE Patients with skull base meningioma (SBM) often require complex surgery around critical neurovascular structures, placing them at high risk of poor health-related quality of life (HRQOL) and possibly neurocognitive dysfunction. As the survival of meningioma patients is near normal, long-term neurocognitive and HRQOL outcomes are important to evaluate, including evaluation of the impact of specific tumor location and treatment modalities on these outcomes. METHODS In this multicenter cross-sectional study including patients 5 years or more after their last tumor intervention, Short-Form Health Survey (SF-36) and European Organisation for Research and Treatment of Cancer (EORTC) QLQ-BN20 questionnaires were used to assess generic and disease-specific HRQOL. Neurocognitive functioning was assessed with standardized neuropsychological assessment. SBM patient assessments were compared with those of 1) informal caregivers of SBM patients who served as controls and 2) convexity meningioma patients. In addition, the authors compared anterior/middle SBM patients with posterior SBM patients and anterior/middle and posterior SBM patients separately with controls. Multivariable and propensity score regression analyses were performed to correct for possible confounders. RESULTS Patients with SBM (n = 89) with a median follow-up of 9 years after the last intervention did not significantly differ from controls (n = 65) or convexity meningioma patients (n = 84) on generic HRQOL assessment. Statistically significantly but not clinically relevantly better disease-specific HRQOL was found for SBM patients compared with convexity meningioma patients. Anterior/middle SBM patients (n = 62) had significantly and clinically relevantly better HRQOL in SF-36 and EORTC QLQ-BN20 scores than posterior SBM patients (n = 27): physical role functioning (corrected difference 17.1, 95% CI 0.2–34.0), motor dysfunction (−10.1, 95% CI −17.5 to −2.7), communication deficit (−14.2, 95% CI −22.7 to −5.6), and weakness in both legs (−10.1, 95% CI −18.8 to −1.5). SBM patients whose primary treatment was radiotherapy had lower HRQOL scores compared with SBM patients who underwent surgery on two domains: bodily pain (−33.0, 95% CI −55.2 to −10.9) and vitality (−18.9. 95% CI −33.7 to −4.1). Tumor location and treatment modality did not result in significant differences in neurocognitive functioning, although 44% of SBM patients had deficits in at least one domain. CONCLUSIONS In the long term, SBM patients do not experience significantly more sequelae in HRQOL and neurocognitive functioning than do controls or patients with convexity meningioma. Patients with posterior SBM had poorer HRQOL than anterior/middle SBM patients, and primary treatment with radiotherapy was associated with worse HRQOL. Neurocognitive functioning was not affected by tumor location or treatment modality.

Neurocognitive deficits among adult road traffic accident victims at the University Teaching Hospital, Lusaka, Zambia

Introduction: Road traffic accidents (RTAs) are of growing public health importance worldwide contributing significantly to the global disease burden thus public health experts worldwide concede that there is a global epidemic of RTAs. Exposure to RTAs may be associated with changes in brain functioning and cognitive performance. Objective: This study sought to contribute to the understanding of the neurocognitive deficits among adult victims of RTAs. Methodology: It is a cross-sectional study (descriptive in nature). Cognitive profiles of the affected participants were assessed by selected tests from the International Neurobehavioral test battery. The quality of life was assessed by application of the World Health Organisation Quality of Life (WHOQOL) questionnaire. The primary data obtained was analyzed using descriptive and inferential statistics using SPSS. Results: Twenty-seven (27) RTA victims out of Thirty (30) had executive functioning impairment with a Domain Deficit Score (DDS) of ≥ 0.5 and all the RTA victims in the study had speed of information processing impairment with a Domain Deficit Score (DDS) of ≥ 0.5. There was no significant statistical gender difference in neurocognitive functioning (Executive functioning F=0.85, P=0.36; Speed of information processing F=0.98, P=0.33). Compromised quality of life among adult victims of road traffic accidents was confirmed (P=0.005). Conclusion: This study shows an association between RTA and neurocognitive functioning in adult victims. Findings of this study show the presence of neuropsychological impairments in the two domains assessed (executive functioning and speed of information processing). The study indicates that RTA significantly compromises the quality of life.