Neurocognitive outcomes and associated clinical factors 5 years after surgery in children with craniosynostosis.

OBJECTIVE: Craniosynostosis involves early closure of one or more sutures, which is known to limit normal cranium growth and interfere with normal brain development. Various surgical methods are used, ranging from minimally invasive strip craniectomy to more extensive whole-vault cranioplasty. This study aimed to evaluate neurocognitive outcomes 5 years after surgical treatment in children with craniosynostosis and to evaluate relevant clinical factors. METHODS: After exclusion of genetically confirmed syndromic craniosynostosis patients, a retrospective review was conducted on 112 nonsyndromic craniosynostosis patients who underwent surgical treatment and follow-up neurocognitive assessment. Ninety-seven patients underwent strip craniectomy with postoperative orthotic helmet therapy, and 15 received other surgical treatment: 4 with distraction osteotomy and 11 with craniofacial reconstruction. Neurocognitive assessment using the Korean Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (K-WPPSI-IV), was performed 5 years postoperatively. Clinical factors were assessed regarding neurocognitive outcomes. RESULTS: The mean age at surgery was significantly younger in the strip craniectomy group (strip craniectomy 4.6 months vs other surgical treatment 18.6 months, p < 0.01). Patients with 2 or more sutures involved were more likely to receive more extensive surgical treatment (16.5% in the strip craniectomy group vs 53.8% in the other group, p < 0.01). Four (3.5%) patients who showed evidence of increased intracranial pressure (ICP) also underwent more extensive surgical treatment. Multivariable linear regression revealed a significant correlation of age at neurocognitive testing (-3.18, 95% CI -5.95 to -0.40, p = 0.02), increased ICP (-34.73, 95% CI -51.04 to -18.41, p < 0.01), and the level of maternal education (6.11, 95% CI 1.01-11.20, p = 0.02) with the Full-Scale Intelligence Quotient (FSIQ). Age at surgery, involvement of 2 or more sutures, and type of operation demonstrated no correlation with FSIQ. Among the 97 patients who underwent strip craniectomy, the FSIQ ranged from mean ± SD 100.2 ± 10.2 (bicoronal) to 110.1 ± 12.7 (lambdoid), and there was no significant difference between the suture groups (p = 0.41). The 5 index scores were all within average ranges based on their age norms. CONCLUSIONS: Age at neurocognitive assessment, increased ICP, and maternal education level showed significant correlations with the neurocognitive function of craniosynostosis patients. Although children with craniosynostosis exhibited favorable 5-year postoperative neurocognitive outcomes across various synostosis sutures, longer follow-up is needed to reveal the incidence of neurocognitive dysfunction in these patients.

The Effect of Temperament on the Association Between Pre-treatment Anxiety and Chemotherapy-Related Symptoms in Patients With Breast Cancer.

OBJECTIVE: Pre-treatment anxiety (PA) before chemotherapy increases complaints of chemotherapy-related symptoms (CRS). The results on the association have been inconsistent, and the effect of temperament remains unclear. We aimed to determine whether PA is a risk factor for CRS and the effect of differing temperaments on CRS. METHODS: This prospective study comprised 176 breast cancer patients awaiting adjuvant chemotherapy post-surgery. We assessed CRS, PA, and temperament using the MD Anderson Symptom Inventory (MDASI), the Hospital Anxiety and Depression Scale, and the short form of the Temperament and Character Inventory-Revised, respectively. The MDASI was re-administered three weeks after the first chemo-cycle. RESULTS: PA showed weak positive correlation with several CRS after the first cycle; no CRS was significantly associated with PA when pre-treatment depressive symptoms and baseline CRS were adjusted in multiple regression analysis. Moderation model analysis indicated that the PA effect on several CRS, including pain, insomnia, anorexia, dry mouth, and vomiting, was moderated by harm avoidance (HA) but not by other temperament dimensions. In particular, PA was positively associated with CRS in patients with low HA. CONCLUSION: The results in patients with low HA indicate that more attention to PA in patients with confident and optimistic temperaments is necessary.

Critical area for memory decline after mesial temporal resection in epilepsy patients.

OBJECTIVE: Mesial temporal lobe epilepsy (MTLE) surgery is associated with a risk of memory decline after surgery, but the effect of the extent and locus of temporal resection on postoperative memory function are controversial. The authors' aim in this study was to confirm if selective resection is effective in preserving memory function and identify critical areas for specific memory decline after temporal resection. METHODS: In this single-center retrospective study, the authors investigated data from patients who underwent unilateral MTLE surgery between 2005 and 2015. Data from 74 MTLE patients (60.8% of whom were female; mean [SD] age at surgery 32 years [8.91 years] and duration of epilepsy 16 years [9.65 years]) with histologically proven hippocampal sclerosis were included. Forty-two patients underwent left-sided surgery. The resection area was manually delineated on each patient's postoperative T1-weighted images. Mapping was performed to see if the resected group, compared with the nonresected group, had worse postoperative memory in various memory domains, including verbal item, verbal associative, and figural memory. RESULTS: Overall, 95.9% had a favorable epilepsy outcome. In verbal item memory, resection of the left lateral temporal area was related to postoperative decline in immediate and delayed recall scores of word lists. In verbal associative memory, resection of the anterior part of the left hippocampus, left parahippocampal area, and left lateral temporal area was related to postoperative decline in immediate recall scores of word pairs. Resection of the posterior part of the left hippocampus, left parahippocampal area, and left lateral temporal area was related to delayed recall scores of the same task. Similarly, in the figural memory, postoperative decline of immediate recall scores was associated with the resection of the anterior part of the right hippocampus, amygdala, parahippocampal area, and superior temporal area, and decline of delayed recall scores was related to resection of the posterior part of the right hippocampus and parahippocampal area. CONCLUSIONS: Using voxel-based analysis, which accounts for the individual differences in the resection, the authors found a critical region for postoperative memory decline that is not revealed in the region-of-interest or groupwise comparison. Particularly, resection of the hippocampus was related to associative memory. In both verbal and visual memory, resection of the anterior part of the hippocampus was associated with immediate recall, and resection of the posterior part of the hippocampus was associated with delayed recall. Therefore, the authors' results suggest that selective resection may be effective in preserving postoperative memory decline.

Neurocognitive profile in children with arachnoid cysts before and after surgical intervention.

OBJECTIVES: Treatment indications for arachnoid cysts are not clear. Some surgeons take improvement in neurocognitive function into account as a surgical indication for arachnoid cysts. However, only a few studies have evaluated the relationship between arachnoid cysts and neurocognitive function. Furthermore, studies that analyze neurocognitive function as an effect of arachnoid cyst surgery are even rarer. The purpose of this study was to analyze the neurocognitive function scores of children with arachnoid cysts before and after surgery and to examine whether surgical treatment led to improved neurocognitive function. METHODS: From June 2009 to August 2012, data for 24 children diagnosed with arachnoid cysts who underwent surgery at Seoul National University Children's Hospital were analyzed. Pre-operative and post-operative cyst volume was assessed and neurocognitive function was tested using the Korean version of the Wechsler Intelligence Scale for Children-Revised (WISC-R) and the Bender-Gestalt Test (BGT). Comparison of pre- and post-operative profiles by laterality of the arachnoid cyst was performed. RESULTS: Patients had age-appropriate full-scale intelligent quotients (FSIQ), verbal IQ (VIQ), and performance IQ (PIQ) pre-operatively, which were maintained after surgery. Of the subtests, Block Design showed significant improvement post-operatively (p = 0.021). This means that visuo-spatial integration and mental construction abilities were improved after surgery. Patients with left or right arachnoid cysts did not show statistically significant changes in FSIQ, VIQ, or PIQ after surgery (110.21 versus 113.95, p = 0.307; 108.92 versus 111.54, p = 0.368; 107.88 versus 111.04, p = 0.152, respectively). Subanalysis showed that the pre- and post-operation VIQ mean scores of the patients with right arachnoid cysts were significantly higher (p < 0.054) than those of the patients with left arachnoid cysts, and there was no significant change after the surgery. INTERPRETATION: There was no significant association among cyst volume reduction, laterality, and clinical neurocognitive function improvement. The present findings indicate a limited role for surgical intervention in improving the intellectual abilities of children with arachnoid cysts.

Delayed transplantation may affect intellectual ability in children.

BACKGROUND: Decline in neurocognitive function is a reported complication in children with chronic illness. Concerns have been increasing that exposure to a major surgery or trauma may negatively affect cognitive performance in children. This study evaluated cognitive function in 43 Korean children who received organ transplantation (Tx), and sought to identify associated clinical factors. METHODS: Pediatric recipients of kidney (KT) or liver Tx (LT) from 1999 to 2011 were recruited for cognitive tests. Cognitive function was evaluated using intelligence quotient (IQ), social quotient (SQ), and Continuous Performance Test using Advanced Test for Attention scores, which reflect attention ability. Intellectual delay was graded as intellectual disability (ID; IQ <70) or low intelligence (LI; IQ<85). Diagnosis for attention-deficit-hyperactivity disorder (ADHD) was made by pediatric psychiatrists. RESULTS: The subjects consisted of 43 pediatric recipients of 28 LT and 15 KT. There were 20 boys (46.5%). Median age was 3.1 years (range, 0.5-15.3 years) at Tx. Median age at cognitive evaluation was 12.9 years (range, 3.4-18.4 years). Median pre-Tx duration of illness was 1.6 years (range, 0-13.5 years). The prevalence of ID, LI, and ADHD was 11.6%, 32.5%, and 32.5%, respectively. On multivariate analysis, longer pre-Tx duration of illness was a significant factor for LI (OR, 1.263; 95%CI: 1.033-1.544, P = 0.023). CONCLUSION: Longer pre-Tx duration may negatively affect intellectual ability in Korean children. Pre-Tx duration was more significant than the age at Tx or total disease duration per se. Early Tx may be beneficial for cognitive function in children.

Environmental tobacco smoke exposure and children's intelligence at 8-11 years of age.

BACKGROUND: Evidence supporting a link between postnatal environmental tobacco smoke (ETS) exposure and cognitive problems among children is mounting, but inconsistent. OBJECTIVES: We examined the relationship between ETS exposure, measured using urine cotinine, and IQ scores in Korean school-aged children. METHODS: The participants were 996 children 8-11 years of age recruited from five administrative regions in South Korea. We performed a cross-sectional analysis of urinary cotinine concentrations and IQ scores obtained using the abbreviated form of a Korean version of the Wechsler Intelligence Scales for Children. Associations were adjusted for potential confounders, and estimates were derived with and without adjustment for mother's Full-Scale IQ (FSIQ) score. RESULTS: After adjusting for sociodemographic and developmental covariates, urinary cotinine concentrations were inversely associated with FSIQ, Verbal IQ (VIQ), Performance IQ (PIQ), vocabulary, math, and block design scores. Following further adjustment for maternal IQ, only the VIQ scores remained significantly associated with urinary cotinine concentration (B = -0.31; 95% CI: -0.60, -0.03 for a 1-unit increase in natural log-transformed urine cotinine concentration; p = 0.03). CONCLUSION: Urine cotinine concentrations were inversely associated with children's VIQ scores before and after adjusting for maternal IQ. Further prospective studies with serial measurements of cotinine are needed to confirm our findings.

Dopaminergic and noradrenergic gene polymorphisms and response to methylphenidate in korean children with attention-deficit/hyperactivity disorder: is there an interaction?

OBJECTIVE: We aimed to investigate the independent and interaction effects of dopamine transporter gene (DAT1), dopamine D4 receptor gene (DRD4), alpha-2A adrenergic receptor gene (ADRA2A), and norepinephrine transporter gene (NET1), with regard to treatment response to methylphenidate (MPH) in attention-deficit/hyperactivity disorder (ADHD). METHODS: The participants of the study were 103 children and adolescents (ages 9.1±2.1 years) diagnosed as having ADHD according to American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria. They were enrolled in an 8-week, open-label trial of MPH. The good responder group was defined as subjects having an ≥50% decrease in the ADHD Rating Scale-IV (ADHD-RS) total score from the baseline, and at the same time a Clinical Global Impressions-Improvement Scale (CGI-I) score of 1 or 2, both at the 8th week of MPH treatment. Multivariate stepwise logistic regression was performed to examine the independent and interaction effects of genotypes on the dichotomized MPH treatment response. RESULTS: Significant interaction effects on MPH response were detected between the genotypes of the DRD4 variable number of tandem repeat (VNTR) polymorphisms and those of either the ADRA2A DraI or the NET1 -3081(A/T) polymorphisms; significant interaction effects were also detected between the genotypes of the ADRA2A DraI polymorphisms and those of either the NET1 G1287A or the NET1 -3081(A/T) polymorphisms (Nagelkerke R(2)=0.40). No significant independent effect of a genotype was detected according to the stepwise logistic regression results. CONCLUSION: The results suggest that genes involved in the dopaminergic and noradrenergic systems might interact to form important predictors of short-term response to MPH.

Neurocognitive profiles of children with moyamoya disease before and after surgical intervention.

BACKGROUND: Clinical research on moyamoya disease (MMD) has focused on symptomatic outcome such as transient ischemic attacks. Neurocognitive function in children critically affects social outcome and is closely related to quality of life. This study is the first to analyze the neurocognitive profiles of children with MMD before and after surgery. METHODS: Sixty-five patients were selected out of 137 who underwent surgery for MMD between 2006 and 2008. The preoperative and postoperative neurocognitive function was tested using the Korean version of the Wechsler Intelligence Scale for Children-Revised (KEDI-WISC-R) and the Bender Gestalt Test (BGT). Pre- and postoperative profiles of patients with or without major infarctions were compared. Patients with borderzone infarctions were analyzed as well. RESULTS: Preoperatively, patients had age-appropriate full-scale intelligence quotient (FSIQ) and verbal IQ (VIQ) scores, which were maintained after surgery. There was significant improvement in performance IQ (PIQ) (p = 0.01) and BGT scores postoperatively (p < 0.01). Among the subtests, Coding showed significant improvement postoperatively (p < 0.01). Preoperatively, patients with major infarctions had significantly lower FSIQ (p < 0.01), VIQ (p = 0.01) and PIQ (p < 0.01) scores compared with those without infarctions. The pre- and postoperative neurocognitive profiles of the patients with borderzone infarctions fell between those of patients with absolutely no infarctions and those of patients with major infarctions. CONCLUSIONS: Considering the natural history of MMD, which leads to a drastic decline in neurocognitive functions, the present findings indicate a role for early active surgery to save the intellectual abilities of children with MMD.

Effect of environmental exposure to lead and tobacco smoke on inattentive and hyperactive symptoms and neurocognitive performance in children.

BACKGROUND: The present study assessed the association between blood lead and urinary cotinine levels and inattentive and hyperactive symptoms and neurocognitive performance in children. METHODS: A total of 667 children (age range 8-11) were recruited from nine schools in five Korean cities. The teachers and parents completed the Korean version of the Attention-deficit/hyperactivity disorder Rating Scales (K-ARS), and the children performed neurocognitive tests. Blood lead and urinary cotinine levels were then measured. RESULTS: The inattentive, hyperactive, and total scores of the teacher-rated K-ARS were positively associated with blood lead level, and the results of the continuous performance test (CPT), Stroop Color-Word Test, and Children's Color Trails Test were inversely associated with urinary cotinine level when controlled for age, gender, father's educational level, maternal IQ, child's IQ, residential area, birth weight, and cotinine (for lead) or lead (for cotinine). The association between blood lead level and commission errors score on the CPT disappeared when the effect of urinary cotinine level was controlled. CONCLUSIONS: These findings indicate that environmental exposure to tobacco smoke in children is associated with poor neurocognitive performance, and low levels of lead are associated with inattention and hyperactivity symptoms.

Changes in neuropsychological functioning following temporal lobectomy in patients with temporal lobe epilepsy.

PURPOSE: This study was conducted to evaluate the changes in neuropsychological functioning in patients with temporal lobe epilepsy (TLE) after temporal lobe resection. METHODS: Fifty-four TLE patients were evaluated before and after surgery using comprehensive neuropsychological tests to assess general intelligence, executive functioning, language, verbal and visual memory, working memory, visuo-spatial ability, attention and motor function. RESULTS: The patients with left TLE showed no impairment of neuropsychological functioning after surgery, with the exception of auditory immediate memory. Furthermore, they showed significant improvement in performance IQ, executive function, working memory, visual memory, attention and psychomotor speed. The patients with right TLE did not show any significant impairment in post-operative neuropsychological functioning. They showed improvements in intellectual and executive functions, language, visual memory, visuo-spatial ability, attention and motor function post-operatively. The patients with hippocampal sclerosis showed greater post-operative improvements than the patients without hippocampal sclerosis regardless of the side. Patients with better pre-operative neuropsychological function had a higher chance of successfully discontinuing all seizure medications after surgery. DISCUSSION: The results of this study suggest that temporal lobectomy does not harm the neuropsychological functioning of patients with intractable TLE and that it improves cognitive functions of the contralateral hemisphere.

Comparison of cognitive function in deaf children between before and after cochlear implant.

OBJECTIVES: This study was conducted to examine improvements of cognitive abilities after cochlear implantation in deaf children. We also examined the psychosocial factors that predict good outcomes of cochlear implantation. DESIGN: A neuropsychological test battery was administered to 17 deaf children (mean age, 7 yr 2 mo) before receiving the cochlear implant, and they were reassessed with the same test at 6-mo follow-up. Their parents completed questionnaires concerning their medical and educational history, parenting style, and parental emotional problems. RESULTS: Deaf children showed marked improvement in speedy and delicate motor coordination and visual organization abilities. Their cognitive functions of comprehension, concentration, and sequential processing, as measured by nonverbal tests, were found to have improved from the levels of borderline to mild mental retardation to that of near-normal range. However, their performances on Information, Comprehension and Similarity, and Mathematics subtests requiring verbal abilities did not show significant changes. Deaf children's working memory improved significantly after cochlear implantation. However, they showed more omission errors in the visual attention test at follow-up than before cochlear implantation. Such inattentiveness for visual stimuli in children post-implantation could be attributed to distractibility of these children toward external noise. Mothers' depression was negatively correlated with scores of acquired knowledge of deaf children. CONCLUSION: At the 6-mo follow-up after cochlear implant, deaf children showed marked improvement in nonverbal cognitive functions and working memory. Conversely, their verbal abilities did not significantly change. Maternal factors were found to be important for predicting the prognosis of cochlear implantation. The absence of a control group precludes the possibility of drawing any firm conclusions because the effect of the implant cannot be teased apart from the effects of maturation and training. Future studies should address this question with the use of appropriate control groups.