Long-term Neurocognitive Outcomes Research Articles

Measures of Physical and Mental Independence Among HIV-Positive Individuals: Impact of Substance Use Disorder.

With the transition of HIV infection from an acute to a chronic disease after the introduction of antiretroviral medications, there has been an increased focus on long-term neurocognitive and other functional outcomes of HIV patients. Thus, we assessed factors, particularly history of a substance use disorder, associated with time to loss of measures of physical or mental independence among HIV-positive individuals. Data were obtained from the National NeuroAIDS Tissue Consortium. Kaplan-Meier and Cox proportional hazards regression analyses were used to estimate the time since HIV diagnosis to loss of independence, and to identify associated risk factors. HIV-positive participants who self-identified as physically (n = 698) or mentally (n = 616) independent on selected activities of daily living at baseline were eligible for analyses. A history of substance use disorder was associated with a higher hazard of loss of both physical and mental independence [adjusted hazard ratio (HR) = 1.71, 95% confidence interval (95% CI): 1.07-2.78; adjusted HR = 1.67, 95% CI: 1.11-2.52, respectively]. After adjusting for substance use disorder and other covariates, older age at diagnosis and female gender were associated with higher hazards of loss of both physical and mental independence, non-white participants had higher hazards of loss of physical independence, whereas participants with an abnormal neurocognitive diagnosis and fewer years of education had higher hazards of loss of mental independence. In summary, history of substance use disorder was associated with loss of measures of both physical and mental independence. The nature of this link and the means to prevent such loss of independence need further investigation.

Long-term cognitive functioning in individuals with tyrosinemia type 1 treated with nitisinone and protein-restricted diet

IntroductionTyrosinemia Type 1 (HT1) is an autosomal recessive disorder caused by a defect in the enzyme fumarylacetoacetate hydroxylase in the tyrosine pathway. Implementation of nitisinone (NTBC) treatment has dramatically improved survival rate of individuals with HT1, yet recent reports on cognitive impairment in treated patients exist. AimsDescribe long-term neurocognitive outcome individuals with HT1 treated with nitisinone and protein restricted diet. MethodologyTwelve individuals with HT1 were analyzed with respect to psychomotor development and cognitive functioning using standardized psychometric tests. Plasma tyrosine and phenylalanine concentrations were also collected and analyzed, as part of the regular HT1 follow up program in our clinic. ResultsDelayed performance in Bayley scale mental developmental index (MDI) was identified in 29% to 38% of the patients assessed at different ages. At preschool age, mean full scale IQ (FSIQ) was 88±16; six out of nine assessed children preformed within normal range, and one child presented with intellectual disability. At school age mean FSIQ was 79±18, three out of nine children preformed within normal range and two showed intellectual disability. Repeated measures showed IQ decline over time in four out of eight patients, all of whom presented with symptoms in their first months of life. Patients that showed no progressive IQ decline were 8months or older at diagnosis, with a mean age of 17months. Significant correlation between Phe/Tyr ratio and FSIQ at school age was identified (r=−0.689; p<0.044). ConclusionSome patients with HT1 treated with nitisinone and protein restricted diet are at risk of presenting developmental delay and impaired cognitive functioning. Patients with early onset of symptoms could be at risk for progressive cognitive functioning decline over time.

Reduced cortical volume and thickness and their relationship to medical and operative features in post-Fontan children and adolescents.

We compared brain cortical and subcortical gray matter volumes and cortical thickness between post-Fontan patients and healthy controls, and examined brain anatomical associations with operative and medical history characteristics. Post-Fontan (n = 128 volumes; n = 115 thickness) and control subjects (n = 48 volumes; n = 45 thickness) underwent brain MRI at ages 10-19 y. Subcortical and cortical volumes and cortical thicknesses were measured for intergroup comparison. Associations between brain measures and clinical measures were assessed in the Fontan group. Widespread, significant reduction in brain volumes and thicknesses existed in the Fontan group compared to controls, spanning all brain lobes and subcortical gray matter. Fontan subjects treated with vs. without the Norwood procedure had smaller volumes in several terminal clusters, but did not differ in cortical thickness. Older age at first operation and increasing numbers of cardiac catheterizations, operative complications, and catheterization complications were associated with lower regional volumes and thicknesses. Increasing numbers of operative complications and cardiac catheterizations were associated with smaller regional volumes in the Norwood group. The post-Fontan adolescent brain differs from the normal control brain. Some of these differences are associated with potentially modifiable clinical variables, suggesting that interventions might improve long-term neurocognitive outcome.

Melatonin and melatonin agonists to prevent and treat delirium in critical illness: a systematic review protocol.

BackgroundDelirium is a syndrome characterized by acute fluctuations and alterations in attention and arousal. Critically ill patients are at particularly high risk, and those that develop delirium are more likely to experience poor clinical outcomes such as prolonged duration of ICU and hospital length of stay, and increased mortality. Melatonin and melatonin agonists (MMA) have the potential to decrease the incidence and severity of delirium through their hypnotic and sedative-sparing effects, thus improving health-related outcomes. The objective of this review is to synthesize the available evidence pertaining to the efficacy and safety of MMA for the prevention and treatment of ICU delirium.MethodsWe will search Ovid MEDLINE, Web of Science, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL to identify studies evaluating MMA in critically ill populations. We will also search http://apps.who.int/trialsearch for ongoing and unpublished studies and PROSPERO for registered reviews. We will not impose restrictions on language, date, or journal of publication. Authors will independently screen for eligible studies using pre-defined criteria; data extraction from eligible studies will be performed in duplicate. The Cochrane Risk of Bias Scale and the Newcastle-Ottawa Scale will be used to assess the risk of bias and quality of randomized and non-randomized studies, respectively. Our primary outcome of interest is delirium incidence, and secondary outcomes include duration of delirium, number of delirium- and coma-free days, use of physical and chemical (e.g., antipsychotics or benzodiazepines) restraints, duration of mechanical ventilation, ICU and hospital length of stay, mortality, long-term neurocognitive outcomes, hospital discharge disposition, and adverse events.We will use Review Manager (RevMan) to pool effect estimates from included studies. We will present results as relative risks with 95% confidence intervals for dichotomous outcomes and as mean differences, or standardized mean differences, for continuous outcomes.DiscussionCurrent guidelines make no pharmacological recommendations for either the prevention or treatment of ICU delirium. This systematic review will synthesize the available evidence on the efficacy and safety of MMA for this purpose, thus potentially informing clinical decision-making and improving patient outcomes.Systematic review registration PROSPERO CRD42015024713 Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-016-0378-2) contains supplementary material, which is available to authorized users.

Hippocampal Dose Constraints for Predicting Long-Term Neurocognitive Outcomes in Young Patients: Mature Data From a Prospective Trial of Conformal Radiation Therapy

Hippocampal Dose Constraints for Predicting Long-Term Neurocognitive Outcomes in Young Patients: Mature Data From a Prospective Trial of Conformal Radiation Therapy

Leukoencephalopathy and long-term neurobehavioural, neurocognitive, and brain imaging outcomes in survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy: a longitudinal analysis

Leukoencephalopathy is observed in some children undergoing chemotherapy for acute lymphoblastic leukaemia, although its effects on long-term outcomes is unknown. This study examines the associations between acute leukoencephalopathy and neurobehavioural, neurocognitive, and brain white matter imaging outcomes in long-term survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy without cranial radiation. In this longitudinal analysis, we used data of children with acute lymphoblastic leukaemia at St Jude Children's Research Hospital (Memphis, TN, USA) who had been treated between June 1, 2000, and Oct 31, 2010. Eligible patients were diagnosed with non-B-cell acute lymphoblastic leukaemia, aged at least 8 years, and survivors with at least 5 years since their initial diagnosis. Brain MRIs obtained during active therapy were systematically coded for leukoencephalopathy using Common Terminology Criteria for Adverse Event version 4. At least 5 years after their diagnosis, survivors completed neurocognitive testing, another brain MRI, and their parents completed neurobehavioural ratings of their child (Behavior Rating Inventory of Executive Function [BRIEF]). Follow-up MRI included diffusion tensor imaging to assess white matter integrity, with indices of fractional anisotropy, axial diffusivity, and radial diffusivity from frontal lobes, parietal lobes, and in the frontostriatal tract. The neuroradiologist, who assessed abnormal MRIs, was masked to both group assignment of survivors and the neurobehavioural and neurocognitive outcomes. The primary outcomes were neurobehavioural function, assessed from completed BRIEF, and neurocognitive performance, measured by direct neurocognitive tests (Delis-Kaplan Executive Function System, Wechsler Intelligence Scale for Children-IV/Wechsler Adult Intelligence Scale-III, Rey-Osterrieth Complex Figure Test, and Lafayette Grooved Pegboard Test). This study had completed enrolment in October, 2014, and is registered as an observational study at ClinicalTrials.gov, number NCT01014195. Between Feb 18, 2010, and Oct 22, 2014, 210 (70%) of 301 eligible survivors participated in our study of whom 190 were evaluable, 162 had an MRI. 56 participants had quantitative brain imaging data and were included in evaluable population analyses. 51 (27%) of the 190 evaluable participants had acute leukoencephalopathy. Compared with population norms, survivors were reported to have more neurobehavioural problems with working memory, organisation, initiation, and planning (p<0·001 for all). Survivors had worse scores than the general population on direct measures of memory span, processing speed, and executive function (p<0·05 for all). Survivors with a history of acute leukoencephalopathy had more neurobehavioural problems than survivors with no history of leukoencephalopathy on organisation (adjusted T-score 56·2 [95% CI 53·3-59·1] vs 52·2 [50·4-53·9], p=0·020) and initiation (55·5 [52·7-58·3] vs 52·1 [50·4-53·8], p=0·045). Survivors with acute leukoencephalopathy also had reduced white matter integrity in the frontostriatal tract at follow-up: lower fractional anisotropy (p=0·069), higher axial diffusivity (p=0·020), and higher radial diffusivity (p=0·0077). A one-unit change in the radial diffusivity index corresponded with a 15·0 increase in raw score points on initiation, 30·3 on planning, and 28·0 on working memory (p<0·05 for all). Acute leukoencephalopathy during chemotherapy treatment, without cranial radiation, for childhood acute lymphoblastic leukaemia predicted higher risk for long-term neurobehavioural problems and reduced white matter integrity in frontal brain regions. Survivors of childhood acute lymphoblastic leukaemia might benefit from preventive cognitive or behavioural interventions, particularly those who develop acute leukoencephalopathy. National Institute of Mental Health, National Cancer Institute, American Lebanese Syrian Associated Charities.

Early Expressive Language Skills Predict Long-Term Neurocognitive Outcomes in Cochlear Implant Users: Evidence from the MacArthur-Bates Communicative Development Inventories.

The objective of the present article was to document the extent to which early expressive language skills (measured using the MacArthur-Bates Communicative Development Inventories [CDI; Fenson et al., 2006]) predict long-term neurocognitive outcomes in a sample of early-implanted prelingually deaf cochlear implant (CI) users. The CDI was used to index the early expressive language skills of 32 pediatric CI users after an average of 1.03 years (SD = 0.56, range = 0.39-2.17) of CI experience. Long-term neurocognitive outcomes were assessed after an average of 11.32 (SD = 2.54, range = 7.08-16.52) years of CI experience. Measures of long-term neurocognitive outcomes were derived from gold-standard performance-based and questionnaire-based assessments of language, executive functioning, and academic skills. Analyses revealed that early expressive language skills, collected on average 1.03 years post cochlear implantation, predicted long-term language, executive functioning, and academic skills up to 16 years later. These findings suggest that early expressive language skills, as indexed by the CDI, are clinically relevant for identifying CI users who may be at high risk for long-term neurocognitive delays and disturbances.

The association of children's mathematic abilities with both adults' cognitive abilities and intrinsic fronto-parietal networks is altered in preterm-born individuals.

Mathematic abilities in childhood are highly predictive for long-term neurocognitive outcomes. Preterm-born individuals have an increased risk for both persistent cognitive impairments and long-term changes in macroscopic brain organization. We hypothesized that the association of childhood mathematic abilities with both adulthood general cognitive abilities and associated fronto-parietal intrinsic networks is altered after preterm delivery. 72 preterm- and 71 term-born individuals underwent standardized mathematic and IQ testing at 8years and resting-state fMRI and full-scale IQ testing at 26years of age. Outcome measure for intrinsic networks was intrinsic functional connectivity (iFC). Controlling for IQ at age eight, mathematic abilities in childhood were significantly stronger positively associated with adults' IQ in preterm compared with term-born individuals. In preterm-born individuals, the association of children's mathematic abilities and adults' fronto-parietal iFC was altered. Likewise, fronto-parietal iFC was distinctively linked with preterm- and term-born adults' IQ. Results provide evidence that preterm birth alters the link of mathematic abilities in childhood and general cognitive abilities and fronto-parietal intrinsic networks in adulthood. Data suggest a distinct functional role of intrinsic fronto-parietal networks for preterm individuals with respect to mathematic abilities and that these networks together with associated children's mathematic abilities may represent potential neurocognitive targets for early intervention.

An Official American Thoracic Society Research Statement: Impact of Mild Obstructive Sleep Apnea in Adults.

Mild obstructive sleep apnea (OSA) is a highly prevalent disorder in adults; however, whether mild OSA has significant neurocognitive and cardiovascular complications is uncertain. The specific goals of this Research Statement are to appraise the evidence regarding whether long-term adverse neurocognitive and cardiovascular outcomes are attributable to mild OSA in adults, evaluate whether or not treatment of mild OSA is effective at preventing or reducing these adverse neurocognitive and cardiovascular outcomes, delineate the key research gaps, and provide direction for future research agendas. Literature searches from multiple reference databases were performed using medical subject headings and text words for OSA in adults as well as by hand searches. Pragmatic systematic reviews of the relevant body of evidence were performed. Studies were incongruent in their definitions of "mild" OSA. Data were inconsistent regarding the relationship between mild OSA and daytime sleepiness. However, treatment of mild OSA may improve sleepiness in patients who are sleepy at baseline and improve quality of life. There is limited or inconsistent evidence pertaining to the impact of therapy of mild OSA on neurocognition, mood, vehicle accidents, cardiovascular events, stroke, and arrhythmias. There is evidence that treatment of mild OSA in individuals who demonstrate subjective sleepiness may be beneficial. Treatment may also improve quality of life. Future research agendas should focus on clarifying the effect of mild OSA and impact of effective treatment on other neurocognitive and cardiovascular endpoints as detailed in the document.

Long-term motor, cognitive and behavioral outcome of acute disseminated encephalomyelitis.

The purpose of this study was to evaluate the long-term motor and neurocognitive outcome of children with acute disseminated encephalomyelitis and to identify prognostic risk factors. The study included 43 children who were hospitalized due to acute disseminated encephalomyelitis during the years 2002-2012. The children underwent full neurological examinations, along with comprehensive neurocognitive and behavioral assessments. Twenty-six (61%) children had different degrees of neurological sequelae after a mean follow-up of 5.5 ± 3.5 years. The most common residual impairment included attention-deficit hyperactivity disorder (44%), behavioral problems (32%), and learning disabilities (21%). Five (12%) children had a full-scale IQ of 70 or less, compared to 2.2% in the general population. Neurocognitive sequelae were found even in children who were considered as fully recovered at the time of discharge. Risk factors for severe neurological sequelae were older age at diagnosis and male gender. We suggest neuropsychological testing and long-term follow-up for all children with acute disseminated encephalomyelitis, even in the absence of neurological deficits at discharge.

ADHD as Sequel to Acute Disseminated Encephalomyelitis.

Investigators from Ruth Children's Hospital, Haifa, and Schneider Medical Center, Petah Tikuah, Israel, evaluated the long-term motor and neurocognitive outcome of 43 children hospitalized during 2002-2012 with acute disseminated encephalomyelitis (ADEM), and identified prognostic risk factors.

Long-Term Neurocognitive, Psychosocial, and Magnetic Resonance Imaging Outcomes in Pediatric-Onset Acute Disseminated Encephalomyelitis

BackgroundAcute disseminated encephalomyelitis (ADEM) is a demyelinating disorder that is usually self-limited. Recent studies have suggested ongoing neurological deficits and neurocognitive impairment in these patients. Little information on the correlation of clinical and neuroimaging markers in ADEM is available. We examined potential clinical factors (e.g., age of onset, acute symptom duration, magnetic resonance imaging [MRI] lesions) and their relation to neurocognitive and psychosocial outcomes. MethodsThis is a retrospective chart review of consecutive pediatric patients diagnosed with ADEM between 2006 and 2012. Patients were evaluated with standard neurological assessment, MRI of the brain, and neuropsychological evaluation. ResultsTwenty-three patients with ADEM with average age at neuropsychological assessment of 10.1 years (±3.50) were included. Five (22.7%) patients were impaired on three or more neurocognitive measures. Psychosocial problems were reported in 20%-40% of patients. Earlier age of onset was correlated with poorer sustained attention and psychosocial problems, whereas acute symptom duration and Expanded Disability Status Scale were not. MRI outcomes were correlated with psychosocial outcomes but not neuropsychological findings. ConclusionsOur findings suggest lingering cognitive and psychosocial deficits in children with a history of ADEM. Clinical features and MRI findings correlated more strongly with psychosocial outcomes than cognitive functioning. Further studies are needed to confirm relationships and other possible contributing factors to lingering deficits.

Neurocognitive outcome after preterm birth: Interest of the follow-up and the systematic evaluation

Preterm children can experience cognitive and behavioral difficulties being able to be responsible for school difficulties going to the academic failure. The aim of this study was to assess the cognitive process while insisting on the early screening from the preschool age. The data arise from the study of files and from the neuropsychological evaluations realized with the premature children followed in a regular way to the service. The premature children with or without motor disabilities more 4 and a half-years, old deficit integrated pre-school and ordinary school were included. The children with severe disabilities in upper limbs and the children having a mental deficiency were excluded. 30 middle-aged children 7 years 5 months have been included. The prematurity is between 27–34. The born term has an effect on the performances in particular on attention and visuo-spatial capacities. The prematurity is a risk factor of the school future of the child. There is specially a negative impact on visuo-spatial and visuo-motor processes and those children present social and behavioral difficulties. It is mandatory to include the neuropsychological evaluation in any follow-up of premature child thanks to tests validated in the Tunisian context. It remains of great importance to identify effective interventions to improve the long-term neurocognitive outcomes.

Magnetoencephalography: Neurophysiologic Imaging for Perinatal Brain Development

Magnetoencephalography (MEG) is a brain imaging modality with considerable promise for understanding early neonatal brain development and its alteration in clinical populations, together with the long-term consequences of premature birth and adverse neonatal events. This article discusses present and potential contributions of MEG to neonatology and neonatal follow-up. We give a brief overview of MEG and discuss its advantages and capabilities. We review fetal MEG and neonatal MEG, including the recent introduction of dedicated neonatal MEG systems. The use of MEG for understanding long-term neurocognitive outcome in populations such as school-aged children born very preterm will be discussed, as well as recent advances in MEG that represent significant opportunities for understanding neonatal brain development. In summary, MEG provides a powerful method to create a noninvasive record of neuronal activity throughout fetal development, neonatal life, and childhood.

Infant formula and neurocognitive outcomes: impact of study end-point selection.

Assessing validity and reliability of end points used in docosahexanoic and arachidonic acids (DHA and ARA) infant formula supplementation trials as an example for addressing the impact of end-point selection and critical need for well-defined, reliable and validated clinical outcome assessments for neurocognitive assessment in neonates and infants. We searched eight electronic databases and reviewed all randomized, controlled human trials using DHA/ARA supplements with neurodevelopment clinical outcomes. We systematically evaluated the validity and reliability of end-point measures based on the criteria for studying nutritional additives recommended by the Institute of Medicine, criteria described in the Food and Drug Administration guidance for clinical outcome assessment, development and literature review. We identified 29 articles that met the selection criteria. The end points that were used for neurodevelopment measures in 23 out of 29 original short-term studies included the Bayley Scale of Infant Development (BSID)-I and -II (n=12), Brunet-Lezine test (n=2), videotape infant's movements (n=1), record time to milestones including sitting, crawling, standing and walking (n=1), problem-solving test (n=2), brainstem auditory-evoked potential (n=1), Touwen examination (n=1), Fagan test of infant intelligence (n=2) and visual habituation protocol (n=1). None of these end points have a long-term predictive property for neurocognitive assessment. Compared with standard infant formula, the beneficial effects of DHA/ARA supplementation on neurodevelopment were reported in 2 out of 12 studies using BSID vs 8 out of 11 studies using other end-point measures. In addition, 6 out of 29 long-term follow-up studies used the end points including Stanford-Binet IQ test (n=1), Wechsler Preschool and Primary Scale of Intelligence (n=4) and Bracken Basic Concept Scale (n=1), which are generally scales of intellectual ability and typically do not change substantively in the short term. None of these long-term follow-up studies demonstrated beneficial effects of DHA/ARA supplementation on neurodevelopment. The choice of end-point measures affects the outcomes of DHA/ARA-supplemented infant formula trials. Available data are currently inadequate to conclude that DHA/ARA supplementation has a clinically meaningful beneficial effect upon neurological development. Although BSID is validated to assess early developmental delays, it is not designed to predict long-term neurocognitive outcome. A well-defined, valid and reliable clinical outcome assessment that measures neurocognitive function in neonates and infants is essential to provide the scientific evidence required for future clinical trials.

Mild traumatic brain injuries in early adolescent rugby players: Long-term neurocognitive and academic outcomes

Background: Information is scant concerning enduring brain injury effects of participation in the contact sport of Rugby Union (hereafter rugby) on early adolescents.Objective: The objective was prospectively to investigate differences between young adolescent male rugby players and non-contact sports controls on neurocognitive test performance over 3 years and academic achievement over 6 years.Method: A sample of boys from the same school and grade was divided into three groups: rugby with seasonal concussions (n = 45), rugby no seasonal concussions (n = 21) and non-contact sports controls (n = 30). Baseline neurocognitive testing was conducted pre-season in Grade 7 and post-season in Grades 8 and 9. Year-end academic grades were documented for Grades 6–9 and 12 (pre-high school to year of school leaving). A mixed model repeated measures ANOVA was conducted to investigate comparative neurocognitive and academic outcomes between the three sub-groups.Results: Compared with controls, both rugby groups were significantly lower on the WISC-III Coding Immediate Recall sub-test. There was a significant interaction effect on the academic measure, with improved scores over time for controls, that was not in evidence for either rugby group.Conclusions: Tentatively, the outcome suggests cognitive vulnerability in association with school level participation in rugby.

Syphilis treatment in the presence of HIV: the debate goes on.

Benzathine Penicillin G has been used to treat syphilis for over 50 years; however, the precise regimen of penicillin for treatment of syphilis in HIV-positive individuals remains a hot topic of debate. Although international guidelines recommend the same treatment for syphilis, regardless of HIV status, there are inconsistencies in prescribing practices among clinicians. Two previous systematic reviews have found limited evidence for enhanced treatment of syphilis in the presence of HIV. However, a growing body of literature indicates that the rate of asymptomatic neurosyphilis may be higher in HIV, and that syphilis infection is associated with poorer long-term neurocognitive outcomes. A number of retrospective studies propose that serological response may be slower, or serological failure may be higher, among HIV-positive individuals, but these studies are limited by high loss to follow-up, high reinfection rates and a focus on serological rather than clinical response. Beyond penicillin, some evidence suggests equivalence of macrolides, cephalosporins and doxycycline, although macrolide resistance is an increasing concern. Until a prospective, randomized study is conducted, inconsistency with treatment will continue. We offer a pragmatic approach to recognizing patients who may require further investigation or neuropenetrative antibiotic treatment.

Neurocognitive Outcome and Quality of Life after Thoracic Aortic Surgery with Deep Hypothermic Circulatory Arrest

Objectives: Deep hypothermic circulatory arrest (DHCA) is a simple and effective method to protect the central nerve system. Despite the advantages of DHCA during aortic surgery, there are few studies about quality of life and changes in cognitive abilities after surgery. The aim of this study is to evaluate the impact of DHCA on long-term neurocognitive outcome.

Early kidney transplantation improves neurocognitive outcome in patients with severe congenital chronic kidney disease.

Renal replacement therapy has become available for the majority of patients suffering from severe congenital chronic kidney disease (CKD). Data on the long-term neurocognitive outcome and the impact of early kidney transplantation (KTx) in this setting is unclear. Neurocognitive outcomes in 15 patients (11 male) with isolated congenital CKD (stage 3-5) requiring KTx at a mean age of 2.8±1.3 were assessed at a mean age of 8.3±1.4years. Patients underwent neurological examination and testing for neuromotor and neurocognitive function using three independent tests. Pre-emptive KTx was performed in six patients, and nine patients were dialyzed prior to KTx for a mean period of 11.1±8.6months. Neuromotor function was abnormal in 8/15 patients. HAWIK-III showed a global intelligence quotient (IQ) of 93.5±11.4 (P=0.05) due to a significantly reduced performance IQ of 89.1±11.3 (P<0.01). In three patients, the global IQ was clinically significantly reduced by >1 SD to <85. In patients with neuromotor dysfunction, performance IQ was lower than in patients with normal neuromotor function (83.8±10.2 vs. 96.2±9.0, P=0.04). Time on dialysis was inversely correlated to verbal IQ (r=0.78, P=0.02). Pre-emptive KTx and duration of dialysis treatment <3months was associated with superior neurocognitive outcome. Early (pre-emptive) KTx results in superior long-term neurocognitive outcome in children with severe congenital CKD.

Neurocognitive outcome in survivors of childhood acute lymphoblastic leukemia: experience at a tertiary care hospital in Korea.

This study was conducted to investigate long-term neurocognitive outcomes and to determine associated risk factors in a cohort of Korean survivors of childhood acute lymphoblastic leukemia (ALL). Forty-two survivors of ALL were compared with 42 healthy controls on measures of a neurocognitive test battery. We analysed potential risk factors (cranial irradiation, sex, age at diagnosis, elapsed time from diagnosis, and ALL risk group) on neurocognitive outcomes. ALL patients had lower, but non-significant full-scale intelligence quotient (FSIQ, 107.2±12.2 vs. 111.7±10.2), verbal intelligence quotient (VIQ, 107.7±13.6 vs. 112.2±11.4), and performance intelligence quotient (PIQ, 106.3±14.2 vs. 110.1±10.7) scores than healthy controls. However, patients treated with cranial irradiation performed significantly lower on FSIQ (102.2±8.1), VIQ (103.3±11.7), and PIQ (101.4±13.2) compared to non-irradiated patients and healthy controls. ALL patients also had poor attention, concentration, and executive functions. Among ALL survivors, cranial irradiation was a risk factor for poor FSIQ, being male was a risk factor for poor PIQ, and younger age was a risk factor for poor attention. Therefore, the delayed cognitive effects of ALL treatment and its impact on quality of life require continuing monitoring and management.