Long-term Intellectual Outcome Research Articles

Long-term intellectual and developmental outcomes after pediatric epilepsy surgery: A systematic review and meta-analysis.

In addition to the primary aim of seizure freedom, a key secondary aim of pediatric epilepsy surgery is to stabilize and, potentially, optimize cognitive development. Although the efficacy of surgical treatment for seizure control has been established, the long-term intellectual and developmental trajectories are yet to be delineated. We conducted a systematic review and meta-analysis of studies reporting pre- and postsurgical intelligence or developmental quotients (IQ/DQ) of children with focal lesional epilepsy aged ≤18 years at epilepsy surgery and assessed at >2 years after surgery. We determined the IQ/DQ change and conducted a random-effects meta-analysis and meta-regression to assess its determinants. We included 15 studies reporting on 341 patients. The weighted mean age at surgery was 7.1 years (range = .3-13.8). The weighted mean postsurgical follow-up duration was 5.6 years (range = 2.7-12.8). The overall estimate of the mean presurgical IQ/DQ was 60 (95% confidence interval [CI] = 47-73), the postsurgical IQ/DQ was 61 (95% CI = 48-73), and the change was +.94 IQ/DQ (95% CI = -1.70 to 3.58, p = .486). Children with presurgical IQ/DQ ≥ 70 showed a tendency for higher gains than those with presurgical IQ/DQ < 70 (p = .059). Higher gains were determined by cessation of antiseizure medication (ASM; p = .041), not just seizure freedom. Our findings indicate, on average, stabilization of intellectual and developmental functioning at long-term follow-up after epilepsy surgery. Once seizure freedom has been achieved, ASM cessation enables the optimization of intellectual and developmental trajectories in affected children.

50 Years Ago in TheJournalofPediatrics: Birth Weight Is More Important than Gestational Age for Long-Term Intellectual Outcome

50 Years Ago in TheJournalofPediatrics: Birth Weight Is More Important than Gestational Age for Long-Term Intellectual Outcome

Neonatal factors related to survival and intellectual and developmental outcome of patients with early-onset urea cycle disorders

PurposeWe aimed to identify prognostic factors for survival and long-term intellectual and developmental outcome in neonatal patients with early-onset urea cycle disorders (UCD) experiencing hyperammonaemic coma. MethodsWe retrospectively analysed ammonia (NH3) and glutamine levels, electroencephalogram and brain images obtained during neonatal coma of UCD patients born between 1995 and 2011 and managed at a single centre and correlated them to survival and intellectual and developmental outcome. ResultsWe included 38 neonates suffering from deficiencies of argininosuccinate synthetase (ASSD, N = 12), ornithine transcarbamylase (OTCD, N = 10), carbamoylphosphate synthetase 1 (CPSD, N = 7), argininosuccinate lyase (ASLD, N = 7), N-acetylglutamate synthase (NAGS, N = 1) or arginase (ARGD, N = 1). Symptoms occurred earlier in mitochondrial than in cytosolic UCD. Sixty-eight percent of patients survived, with a mean (standard deviation-SD) follow-up of 10.4 (5.3) years. Mortality was mostly observed in OTCD (N = 7/10) and CPSD (N = 4/7) patients. Plasma NH3 level during the neonatal period, expressed as area under the curve, but not glutamine level was associated with mortality (p = .044 and p = .610). 62.1% of the patients had normal intellectual and developmental outcome. Intellectual and developmental outcome tended to correlate with UCD subtype (p = .052). No difference in plasma NH3 or glutamine level during the neonatal period among developmental outcomes was identified. EEG severity was linked to UCD subtypes (p = .004), ammonia levels (p = .037), duration of coma (p = .043), and mortality during the neonatal period (p = .020). Status epilepticus was recorded in 6 patients, 3 of whom died neonatally, 1 developed a severe intellectual disability while the 2 last patients had a normal development. ConclusionUCD subtypes differed by survival rate, intellectual and developmental outcome and EEG features in the neonatal period. Hyperammonaemia expressed as area under the curve was associated with survival but not with intellectual and developmental outcome whereas glutamine was not associated with one of these outcomes. Prognostic value of video-EEG monitoring and the association between status epilepticus and mortality should be assessed in neonatal hyperammonaemic coma in further studies.

Long-Term Intellectual and Fine Motor Outcomes in Spina Bifida Are Related to Myelomeningocele Repair and Shunt Intervention History.

Lifespan outcomes of simultaneous versus sequential myelomeningocele repair and shunt placement or effects of repeated shunt revisions on specific domains of IQ or fine motor dexterity are largely unknown. The current study addressed these gaps in a large cohort of children and adults with spina bifida myelomeningocele (SBM). Participants between 7 and 44 years of age with SBM and shunted hydrocephalus were recruited from international clinics at two time points. Each participant completed a standardized neuropsychological evaluation that included estimates of IQ and fine motor dexterity. Simultaneous versus sequential surgical repair and number of shunt revisions were examined in relation to long-term IQ and fine motor scores. Simultaneous myelomeningocele repair and shunting were associated with more frequent shunt revisions, as well as to lower Full Scale and verbal IQ scores, controlling for number of shunt revisions. More shunt revisions across study time points were associated with higher nonverbal IQ (NVIQ) scores. No effects were observed on fine motor dexterity. Findings indicate generally greater influence of surgery type over shunt revision history on outcomes in well-managed hydrocephalus. Findings supported apparent, domain-specific benefits of sequential compared to simultaneous surgery across the lifespan in SBM. Higher NVIQ scores with greater number of additional shunt revisions across surgery type supported positive outcomes with effective surgical management for hydrocephalus.

Intellectual outcomes of extremely preterm infants at school age.

The survival rate of extremely preterm (EP) infants (<28 weeks of gestation) has improved dramatically, and there is great interest in the long-term prognosis. The aim of this study was to elucidate the influence of prenatal and postnatal care on long-term intellectual outcome in EP infants. Subjects were EP infants admitted to the neonatal intensive care unit from 1982 to 2005. The survival rate and neurodevelopmental outcomes at 6 years of age were analyzed for the periods 1982-1991 (period 1) and 1992-2005 (period 2). Logistic regression analysis was performed to examine risk factors for intellectual impairment. Survival rate improved significantly from 84.5% (period 1) to 92.4% (period 2; P = 0.007). Follow-up data were obtained from 92 children in period 1 (69.7% of survivors) and from 245 in period 2 (72.3% of survivors). The incidence of intellectual impairment increased from 16.3% (period 1) to 31.0% (period 2). Significant factors associated with intellectual impairment were period 2 (OR, 3.53; P = 0.007), supplemental oxygen at 36 weeks' corrected age (OR, 2.22; P = 0.012), number of days in the hospital (OR, 1.01; P = 0.012), intraventricular hemorrhage (IVH; OR, 3.05; P = 0.024), and later tube-feeding commencement date (OR, 1.10; P = 0.032). Despite an increase in survival rate, the rate of intellectual impairment increased in period 2. According to risk factor analysis, reducing the incidence of chronic lung disease and/or apnea, IVH, and nutritional deprivation is a key factor in improving the intellectual outcomes of EP infants.

Development of intelligence 4 to 11years after paediatric epilepsy surgery.

Little is known about the long-term intellectual outcomes following paediatric epilepsy surgery. Change is not likely within the first 2years following surgery, and the few studies of longer term outcomes have yielded inconsistent results. This study addressed this issue by examining a large group of surgical and non-surgical patients at baseline and after 4-11years. Participants were 97 patients (mean age 20.08 [SD: 4.44]years) with childhood-onset intractable epilepsy; 61 had undergone resective epilepsy surgery. Participants underwent neuropsychological testing with the age-appropriate Wechsler Intelligence Scale, generating Full Scale, Performance and Verbal IQs, and Working Memory and Processing Speed indices. In total 54% of the surgical and 39% of the non-surgical patients were seizure free in the preceding 12months (p>.05); however, surgical patients did achieve seizure freedom sooner and used fewer medications at follow-up. Surgical status was not associated with any cognitive domain. However, with the exception of processing speed, significant seizure status×time interaction effects were evident and seizure-free patients had higher scores at follow-up. Regression analyses additionally showed that low pre-operative scores were predictive of improvement overtime, whereas high pre-operative scores were predictive of high scores at follow-up. The results show similar intellectual outcomes for surgical and non-surgical paediatric patients. Four to 11years after paediatric epilepsy surgery, seizure freedom, whether attained through epilepsy surgery or other means, was found to be associated with intellectual improvements. Seizure status and baseline scores were the most consistent predictors.

Disruption of White Matter Integrity in Adult Survivors of Childhood Brain Tumors: Correlates with Long-Term Intellectual Outcomes.

BackgroundAlthough chemotherapy and radiation treatment have contributed to increased survivorship, treatment-induced brain injury has been a concern when examining long-term intellectual outcomes of survivors. Specifically, disruption of brain white matter integrity and its relationship to intellectual outcomes in adult survivors of childhood brain tumors needs to be better understood.MethodsFifty-four participants underwent diffusion tensor imaging in addition to structural MRI and an intelligence test (IQ). Voxel-wise group comparisons of fractional anisotropy calculated from DTI data were performed using Tract Based Spatial Statistics (TBSS) on 27 survivors (14 treated with radiation with and without chemotherapy and 13 treated without radiation treatment on average over 13 years since diagnosis) and 27 healthy comparison participants. Whole brain white matter fractional anisotropy (FA) differences were explored between each group. The relationships between IQ and FA in the regions where statistically lower FA values were found in survivors were examined, as well as the role of cumulative neurological factors.ResultsThe group of survivors treated with radiation with and without chemotherapy had lower IQ relative to the group of survivors without radiation treatment and the healthy comparison group. TBSS identified white matter regions with significantly different mean fractional anisotropy between the three different groups. A lower level of white matter integrity was found in the radiation with or without chemotherapy treated group compared to the group without radiation treatment and also the healthy control group. The group without radiation treatment had a lower mean FA relative to healthy controls. The white matter disruption of the radiation with or without chemotherapy treated survivors was positively correlated with IQ and cumulative neurological factors.ConclusionsLower long-term intellectual outcomes of childhood brain tumor survivors are associated with lower white matter integrity. Radiation and adjunct chemotherapy treatment may play a role in greater white matter disruption. The relationships between white matter integrity and IQ, as well as cumulative neurological risk factors exist in young adult survivors of childhood brain tumors.

Cumulative neurological factors associated with long-term outcomes in adult survivors of childhood brain tumors

Prior research has demonstrated the reliability and validity of the Neurological Predictor Scale (NPS) in relation to childhood brain tumor survivor outcomes; however, its use has not been examined in adult long-term survivors. The current study examines the concurrent validity of the NPS with long-term intellectual and adaptive outcomes in adult survivors of childhood brain tumors relative to individual variables alone. A total of 68 adult survivors of childhood brain tumors (M = 24 years old, SD = 4) almost 16 years post diagnosis (SD = 6) completed intellectual evaluations using the Wechsler Abbreviated Scale of Intelligence (WASI). Survivors’ adaptive functioning skills were assessed via informant structured clinical interviews (SIB-R). NPS scores were computed from data acquired from medical records. The NPS was significantly associated with intellectual (R2 = 0.208, p < .05) and adaptive outcomes (R2 = 0.30, p < .05) over and above individual risk factors. Approximately 18% of long-term survivors were identified as impaired in intellectual outcomes, and 29% were identified as impaired in adaptive functioning in everyday life skills. The NPS quantifies the cumulative effects of treatment and neurological sequelae experienced by both short- and long-term survivors of childhood brain tumors. It is a useful and easy measure to employ in clinical research that focuses on quantifying the neurological risk factors associated with long-term intellectual and adaptive functioning outcomes in adult survivors of childhood brain tumors.

Unprovoked Status Epilepticus: The Prognosis for Otherwise Normal Children With Focal Epilepsy

To document the effect of unprovoked status epilepticus (SE) on the prognosis for otherwise normal children with focal epilepsy. From the Nova Scotia Childhood Epilepsy Study (population-based), we identified patients with focal epilepsy, normal intelligence, and neurologic examination and follow-up ≥ 10 years. We compared those with and without unprovoked SE. One hundred eighty-eight cases had a mean follow-up of 27 ± 5 years with no deaths from SE. Thirty-nine (20%) had SE, 19 of whom experienced their first seizure. The number of episodes of SE was 1 in 27 patients (69%) and 2 to 10 in 12 patients. At onset 9 of 39 (23%) SE patients and 35 of 149 (23%) no-SE patients had specific learning disorders. At follow-up, 11 (28%) SE and 49 (33%) no-SE patients had learning disorders (P = not statistically different [ns]). Grades repeated, high school graduation, and advanced education did not differ. The number of antiepileptic drug (AED) used throughout the clinical course was the same: 22/39 (56%). SE patients used ≤ 2 AEDs versus 99 of 149 (64%) no-SE patients (P = .2). The distribution of patients using 3 to 11 AEDs was similar. The remission rate (seizure-free without AEDs at the end of follow-up) for SE patients was 24 of 39 (61%) versus 99 of 149 (66%) in no-SE (P = .5). Intractable epilepsy occurred in 15% SE and 11% of no-SE cases. SE often recurs but apparently has little influence on long-term intellectual and seizure outcome in normally intelligent children with focal epilepsy.

Long-term Intellectual Outcome of Traumatic Brain Injury in Children: Limits to Neuroplasticity of the Young Brain?

Trauma is the most frequent cause of acquired brain injury in young children, but few studies of long-term intellectual outcome have been published. With a high incidence of inflicted injury in young children, long-term outcome data on accidental traumatic brain injury (TBI) in young children is especially sparse. In these 2 reports from the same children's hospital, there are noteworthy differences in the intellectual outcomes. Crowe et al1 followed up 53 children who had sustained TBI (20 mild, 33 moderate to severe) before age 3 years and tested 27 healthy children with similar demographic features for comparison. Two-thirds of the children who had sustained moderate to severe TBI were injured in falls. Socioeconomic level of the family at the time of injury was the strongest predictor of intellectual level at follow-up when the children were 4 to 6 years old. The nonsignificant effect of acute TBI severity and the generally average range of intellectual function are unexpected findings. However, the classification … Address correspondence to Harvey S. Levin, PhD, Baylor College of Medicine, 1709 Dryden Rd, Suite 1200, Houston, TX 77030. E-mail: hlevin{at}bcm.edu

Long-term intellectual outcome after temporal lobe surgery in childhood

Temporal lobe resection is an established treatment for medication-resistant temporal lobe epilepsy, which in recent years has increasingly been performed in children. However, little is known about the long-term outcome in these children. The aim of this study was to characterize intellectual and psychosocial functioning of children after temporal lobe resection as they progress into late adolescence and adulthood. We report the long-term follow-up of 42 children who underwent temporal lobe surgery after an average postoperative period of 9 years. Longitudinal change in IQ was documented, psychosocial outcome including quality of life was assessed, and preoperative and postoperative T1-weighted MRI brain scans were evaluated quantitatively. A well-matched nonsurgical comparison group of 11 children with similar clinical characteristics was also assessed. At follow-up, 86% of the surgical group were seizure-free, and 57% were no longer taking antiepileptic medication. A significant increase in IQ was found in the surgical group after an extended follow-up period of >5 years. This IQ change was not found in the nonsurgical comparison group. IQ increases were associated with cessation of antiepileptic medication and changes in MRI-derived gray matter volume. The surgical group also reported better psychosocial outcome including quality of life, which was more strongly associated with seizure freedom rather than surgery per se. Surgery for temporal lobe epilepsy performed in childhood results in excellent long-term seizure control and favorable cognitive outcome along with positive effects on brain development. This study provides Class III evidence that temporal lobectomy in children with temporal lobe epilepsy is associated with improved long-term intellectual outcomes compared with those undergoing standard medical treatment.

Maternal blood glucose in diabetic pregnancies and cognitive performance in offspring in young adulthood: a Danish cohort study

Maternal diabetes is a known risk factor for perinatal complications, but there are little data on consequences for long-term intellectual outcome in offspring. We assess cognitive performance in military conscripts according to maternal blood glucose levels during pregnancy. We identified a cohort of 60 Danish male offspring of insulin-treated diabetic mothers born between 1976 and 1984 and followed this cohort to military conscription. From medical records, we extracted data on all available values of maternal blood glucose categorized as fasting and non-fasting and by day in pregnancy, together with maternal White class, smoking habits and socio-economic status. The main outcome was cognitive performance at conscription measured with a validated intelligence test. The association between maternal blood glucose level and cognitive performance was assessed by multivariate linear regression and a fitted fractional polynomial. Median fasting blood glucose values in the second half of pregnancy was negatively associated with cognitive scores at conscription [adjusted coefficient -1.7; 95% confidence interval (CI) -3.0; -0.4]. Restriction to only first-born sibling slightly strengthened the association (coefficient -1.9; 95% CI -3.3; -0.5), but after exclusion of two pregnancies with the blood glucose > 10 mmol/l the association became insignificant (coefficient -0.6; 95% CI -2.6; 1.4). Maternal blood glucose level during diabetic pregnancy is negatively associated with cognitive performance in offspring at military conscription. In pregnancies with fasting blood glucose levels below 10 mmol/l, the association is weak and considered to be without clinical relevance.

Children With Congenital Hypothyroidism: Long-Term Intellectual Outcome After Early High-Dose Treatment

We aim to determine long-term intellectual outcome of adolescents with early high-dose treated congenital hypothyroidism (CH). Sixty-three prospectively followed children with CH were assessed at age of 14 y with the Wechsler Intelligence Scale for Children-Revised and compared with 175 healthy controls. Median age at onset of treatment was 9 d (range 5-18 d) and median starting dose of levothyroxine (L-T4) was 14.7 microg/kg/d (range 9.9-23.6 microg/kg/d). Full-scale intelligence quotient (IQ) was significantly lower than in controls after adjustment for socioeconomic status (SES) and gender (101.7 versus 111.4; p < 0.0001). Children with athyreosis had a lower performance IQ than those with dysgenesis (adjusted difference 7.6 IQ scores, p < 0.05). Lower initial thyroxine (T4) levels correlated with poorer IQ (r = 0.27, p = 0.04). Lower SES was associated with poorer IQ, in particular in children with CH (interaction, p = 0.03). Treatment during childhood was not related to IQ at age 14 y. Adolescents with CH manifest IQ deficits when compared with their peers despite early high-dose treatment and optimal substitution therapy throughout childhood. Those adolescents with athyreosis and lower SES are at particular risk for adverse outcome. Therefore, early detection of intellectual deficits is mandatory in children with CH.

Children With Congenital Hypothyroidism: Long-Term Intellectual Outcome After Early High-Dose Treatment

Children With Congenital Hypothyroidism: Long-Term Intellectual Outcome After Early High-Dose Treatment

Cognitive Function and Army Rejection Rate in Young Adult Male Offspring of Women With Diabetes: A Danish Population-Based Cohort Study

Perinatal complications are more frequent in cases of maternal diabetes, but little is known about the long-term intellectual outcome of offspring born to diabetic mothers. This study followed a cohort of Danish males born in the years 1976–1984 whose mothers were diabetic. These 282 subjects were followed up to the time of military conscription along with 870 population-based control subjects. The instrument used to gauge intelligence was the Boerge-Prien test, a 45-minute validated measure whose results correlate closely with those obtained using the Wechsler Adult Intelligence Scale. The rejection rate was 52.5% for diabetes-exposed subjects and 45.4% for control subjects. The risk difference was 7.3%, with a 95% confidence interval (CI) of 0.6 to 14.01. Analysis of the medical reasons for rejection failed to disclose diagnoses that could be related to cognitive performance. Among those who were not rejected, mean cognitive scores were 41.4 units (95% CI, 40.2–42.6) in diabetes-exposed individuals and 42.7 units (95% CI, 42.0–43.4) in control subjects. The findings were not altered when stratifying subjects by gestational age at birth or Apgar score. In a subgroup of 39 pregnancies with available data, a 1% point increase in maternal AIC (glycosylated hemoglobin) was associated with a 2.6% point decrease in cognitive score (95% CI, 1.8–4.8). Men whose maternal AIC was less than 7% had cognitive scores identical to those of control subjects. These findings point to a real, if minor, reduction in intelligence in young adult males whose mothers are diabetic. The negative association between AIC and cognitive scores stresses the need to strive for optimal metabolic control in diabetic women who are—or are planning to become—pregnant.

Cognitive Function and Army Rejection Rate in Young Adult Male Offspring of Women With Diabetes

While maternal diabetes is a known risk factor for perinatal complications, there is little data on long-term intellectual outcome in offspring. We compare the rejection rate and cognitive functioning of military conscripts according to maternal diabetes status during pregnancy. We identified a cohort of Danish male offspring of diabetic mothers born between 1976 and 1984 and followed this cohort together with population-based control subjects to military conscription. The main outcome was army rejection rate and cognitive function measured with a validated intelligence test. The army rejection rate was 52.5% among 282 men whose mothers had diabetes during pregnancy and 45.4% among 870 control subjects (risk difference 7.3 [95% CI 0.6-14.0]). Mean cognitive scores were 41.4 units (95% CI 40.2-42.6) in diabetes-exposed conscripts and 42.7 units (42.0-43.4) in control subjects. Stratification by gestational age, Apgar score, and White's class (A-F) did not change the associations. In a subgroup analysis using available data on A1C levels during pregnancy, this variable was inversely associated with cognitive functioning. In men with maternal A1C <7%, cognitive scores were identical to those in control subjects. The slightly higher army rejection rate in men with maternal diabetes indicates higher morbidity. The identical cognitive functioning in cases of well-controlled maternal diabetes compared with that in control subjects is reassuring, but the negative association between A1C and cognitive score highlights the importance of striving for optimal metabolic control in diabetic women who are or plan to become pregnant.

Associations of Birth Defects with Adult Intellectual Performance, Disability and Mortality: Population-based Cohort Study

Infants born with birth defects have poorer outcomes in terms of mortality and disability, but the long-term intellectual outcome in children with birth defects is generally unknown. We assessed the long-term associations of various birth defects with mortality and disability, and evaluated whether high mortality and disability were reflected in impaired intellectual performance at age 18. In this nationwide cohort study, records of 9,186 males with and 384,384 without birth defects, registered in the Medical Birth Registry of Norway (1967-1979) were linked to the National Conscript Service (1984-1999). Mortality and disability before military draft, and intelligence test score at conscription were the main outcome measures. Males with birth defects had a relative risk for disability of 6.0 compared with males without defects. Disability was low within categories of birth defects associated with low mortality, and high within defect categories associated with high mortality. The relative risk for not being drafted was highest if maternal educational level was low. Heart defects and cleft palate were the only subgroups in which intellectual performance was lower after adjustment for maternal education, maternal age, marital status and birth order. In particular, intellectual performance was not impaired among those with multiple compared with single defects. We conclude that for the majority of birth defect categories in the present birth cohort, our hypothesis that intellectual performance would be impaired was not confirmed. Thus, there seems to be little reason to fear an adverse intellectual outcome in non-disabled surviving infants with birth defects.

Proton magnetic resonance spectroscopy (1H‐MRS) of the brain following high‐dose methotrexate treatment for childhood cancer

Background To avoid the late sequelae associated with cranial radiation therapy in childhood, intermediate- or high-dose intravenous methotrexate (HDMTX) has found increasing application as a means of preventing the development of overt central nervous system disease in childhood acute leukaemia. However, acute and chronic neurotoxicity has been described following HDMTX therapy, and the long-term intellectual outcome in children treated in this way is inadequately documented. Proton magnetic resonance spectroscopy (1H-MRS) of the brain is a noninvasive, quantitative way of assessing aspects of cerebral metabolism, which has not previously been applied to the study of children undergoing central nervous system directed therapy. Procedure To evaluate the potential role of 1H-MRS in the investigation of related neurotoxicity, 11 children who had received HDMTX (cumulative dose 6–96 g/m2) underwent localised 1H-MRS, magnetic resonance imaging. Neuropsychological assessments were performed on the children who had more than 1 year of follow-up time since last methotrexate treatment. Control 1H-MRS studies on 11 adult and 6 young volunteers were undertaken. Eight patients had spectra of adequate quality. Comparisons between 1H-MRS metabolite ratios and normal controls were made. Results Patients had a low choline/water ratio compared to controls (P < 0.01). No differences between patient and control NAA/water, Cr/water, Naa/Cr, and Cho/Cr ratios were seen. Overall, 3 patients had abnormal white matter changes on MRI. The mean IQ of the patients (104.1) was in the normal range. Conclusions It is postulated that choline depletion in the brains of these patients may reflect subclinical disturbances of myelin metabolism as a result of methotrexate therapy and may represent a possible avenue of treatment in patients with clinical chronic methotrexate-related neurotoxicity. Med. Pediatr. Oncol. 35:28–34, 2000. © 2000 Wiley-Liss, Inc.

Proton magnetic resonance spectroscopy ((1)H-MRS) of the brain following high-dose methotrexate treatment for childhood cancer.

To avoid the late sequelae associated with cranial radiation therapy in childhood, intermediate- or high-dose intravenous methotrexate (HDMTX) has found increasing application as a means of preventing the development of overt central nervous system disease in childhood acute leukaemia. However, acute and chronic neurotoxicity has been described following HDMTX therapy, and the long-term intellectual outcome in children treated in this way is inadequately documented. Proton magnetic resonance spectroscopy ((1)H-MRS) of the brain is a noninvasive, quantitative way of assessing aspects of cerebral metabolism, which has not previously been applied to the study of children undergoing central nervous system directed therapy. To evaluate the potential role of (1)H-MRS in the investigation of related neurotoxicity, 11 children who had received HDMTX (cumulative dose 6-96 g/m(2)) underwent localised (1)H-MRS, magnetic resonance imaging. Neuropsychological assessments were performed on the children who had more than 1 year of follow-up time since last methotrexate treatment. Control (1)H-MRS studies on 11 adult and 6 young volunteers were undertaken. Eight patients had spectra of adequate quality. Comparisons between (1)H-MRS metabolite ratios and normal controls were made. Patients had a low choline/water ratio compared to controls (P < 0.01). No differences between patient and control NAA/water, Cr/water, Naa/Cr, and Cho/Cr ratios were seen. Overall, 3 patients had abnormal white matter changes on MRI. The mean IQ of the patients (104.1) was in the normal range. It is postulated that choline depletion in the brains of these patients may reflect subclinical disturbances of myelin metabolism as a result of methotrexate therapy and may represent a possible avenue of treatment in patients with clinical chronic methotrexate-related neurotoxicity.

Long-term intellectual outcome in children with posterior fossa tumors according to radiation doses and volumes

Purpose: To analyze the relationship between craniospinal irradiation (CSI) and intellectual outcome in children with posterior fossa (PF) tumors. Methods and Materials: A neuropsychological evaluation was performed retrospectively in 31 children, aged 5–15 years, who had received radiotherapy for PF tumors, and who had been off therapy for at least 1 year. Factors evaluated for impact on intellectual outcome were: socioeconomic status, disease presentation, histology, complications, chemotherapy, age at radiotherapy, interval between radiotherapy and testing, and radiation doses and volumes. Patients were divided into 3 subgroups according to the CSI doses (0 Gy [ i.e., PF irradiation only], 25 Gy, and 35 Gy), with 11, 11, and 9 patients, respectively. Results: Long-term cognitive impairment occurred in most of the patients, even after PF irradiation only. Moreover, there was a significant correlation between the full-scale IQ score (FSIQ) and the CSI dose, with mean FSIQ scores at 84.5 (SD = 14.0), 76.9 (SD = 16.6), and 63.7 (SD = 15.4) for 0 Gy, 25 Gy, and 35 Gy of CSI, respectively. A marked drop in verbal comprehension scores was noted in children who had received the higher dose. Conclusion: This preliminary study further supports the rationale for de-escalation of CSI doses and volumes in standard-risk PF tumors.