Sally M. Kuehn

Cognitive Changes in Children Treated for Acute Lymphoblastic Leukemia With Chemotherapy Only According to the Pediatric Oncology Group 9605 Protocol

The purpose of this study was to examine cognitive functioning and neuroimaging in children with leukemia treated with the Pediatric Oncology Group 9605 protocol at the Childrens Hospital of Eastern Ontario. Mean age at diagnosis was 4.88 ± 2.54 years. The mean (n = 24) Wechsler Verbal and Performance IQ fell in the low-average range (87.33 ± 15.69 and 84.83 ± 19.11, respectively). Mean (n = 20) Verbal and Visual Memory Indexes of 82.95 ± 15.46 and 88.30± 10.80, respectively, were obtained. The proportion of scores on measures of intelligence and memory falling > 1 SD below the normative mean was substantially higher than expected. Paired t-test suggested that Wechsler Verbal IQ and memory remained stable, whereas Wechsler Performance IQ declined significantly. The results of growth curve analyses replicated these findings and suggested a significant adverse effect of cumulative dosage of intrathecal methotrexate on estimated Wechsler Performance IQ. Although only two children experienced seizures, 78% of the group showed leukoencephalopathy on at least one magnetic resonance image. Reliance on seizures as a predictor of leukoencephalopathy might underestimate the incidence of neurotoxicity. (J Child Neurol 2005;20:129—133).

Medical and cognitive outcome in children with traumatic brain injury.

BACKGROUND Head injury is an important cause of morbidity and mortality in pediatrics. Comprehensive studies on outcome are scarce despite significant clinical concern that multiple areas of functioning may be impaired following moderate to severe head injury. The literature suggests that sequelae include not only medical problems but also impairments in cognitive functioning. METHODS A retrospective medical and psychology chart review of patients, age 1-18 years, admitted to the Childrens Hospital of Eastern Ontario with moderate (Glasgow Coma Scale [GCS] 9-12) or severe head injury (GCS < or = 8) from November 1, 1993 until December 31, 1998 was conducted. Correlations were performed between medical variables (i.e., GCS, Pediatric Risk of Mortality [PRISM] III score, duration of ICU and hospital stay) and measures of intelligence and memory functioning. RESULTS Eighty-three children age 1 to 18 were included. Seventy percent of the children were classified as having a severe head injury. There was a mortality rate of thirteen percent. Younger age at injury, lower GCS, and higher PRISM III scores predicted higher mortality. Medical complications were documented systematically. Forty-four patients underwent at least one cognitive assessment and 17 of these children had intelligence testing at three points in time: baseline (< four months), early recovery (five to 15 months) and follow-up (16 to 38 months). The mean intelligence and memory scores fell within the average range at the latest point in follow-up. For those children who underwent three serial assessments, the mean verbal and performance IQ fell within the low average range at baseline improving significantly to fall within the average range by early recovery. Continued improvements were apparent in verbal memory beyond early recovery, with the mean obtained at follow-up falling within 1 SD of the normative mean. Despite the return to normal ranges for the group means the proportion of scores falling below 1.5 standard deviations from the mean was greater than population norms for verbal IQ, performance IQ and verbal memory. Lower GCS scores and longer duration of stay in ICU or hospital were predictive of lower nonverbal intelligence. Lower GCS was also predictive of lower visual memory scores. CONCLUSIONS This study describes a population of Canadian children who suffered moderate or severe traumatic brain injury. Initial GCS was the best predictor of mortality and cognitive outcome. These children demonstrated a temporal improvement in intelligence and memory functioning, with their mean performance on these cognitive measures falling within the average range at 16 to 38 months postinjury, although there was considerable variability in the outcomes between individuals.

Are there changes in intelligence and memory functioning following surgery for the treatment of refractory epilepsy in childhood

HeadingAbstract Materials and methods. A retrospective review of the neuropsychological and medical variables of 26 children who underwent a cortical resection as part of the management of their medically refractory epilepsy was conducted. Neuropsychological variables included pre- and postoperative measures of intelligence (Wechsler Scales) and memory functioning (Wide Range Assessment of Memory and Learning). Medical variables included age at onset of seizures, age at surgery, site of resection, and degree of seizure control postoperatively. Results. Twenty patients had temporal resections (13 left-sided). Six had extratemporal resections. In this series, cortical resection as treatment of epilepsy in children did not result in a significant change in performance on measures of intelligence or memory functioning. No significant correlation was found between the medical variables and the neuropsychological outcome.

Cognitive sequelae in children with posterior fossa tumors

Late effects of radiotherapy on intellectual functioning have been well documented in children treated for posterior fossa tumors. Other aspects of cognitive functioning, such as memory, have not been adequately assessed in this population. This retrospective review reports on 15 children diagnosed with medulloblastoma or cerebellar astrocytoma who were administered a norm-referenced standardized test of memory functioning (i.e., Wide Range Assessment of Memory and Learning) an average of 3.5 years after treatment. Analyses revealed that sample means of IQ and memory were significantly lower than those of the normative population. No significant differences were found between the verbal and nonverbal IQ, or verbal and visual memory. Age at diagnosis accounted for a significant proportion of variability in the intelligence ratings but not in the memory indexes. The IQ scores of children less than 6 years of age at diagnosis were significantly lower than those of children diagnosed when over 6 years of age. Given the substantial variability within the older age group, there was insufficient power to detect true differences between memory index means for children by age at diagnosis. Follow-up assessments over 5 years may better identify the long-term effects of radiotherapy on memory functioning.

Medulloblastoma in children – the Ottawa experience

Abstract A retrospective review of 36 children diagnosed with medulloblastoma in the Ottawa area between 1974 and 1997 was completed (mean age 7.8±4.2 years, range 1.2–15.3 years). Via a suboccipital approach, complete tumor resection was achieved in 75% and subtotal resection (>90%) in 25%, without any operative mortality. The tumor was located in the vermis in 39% and in the cerebellar hemisphere in 11%; it occupied both locations in 50%. In 47% of the children a ventriculoperitoneal shunt was required. Postoperatively, craniospinal radiation at 3600 cGy with a boost to the posterior fossa was administered. Chemotherapy was used in 56%. The 1-year survival rate was 92%, and survival plateaued at 54% at 5 years. Children less than 3 years of age fared worse than those over 3 years old. While the male-to-female ratio was 1.6:1, there was no gender difference in survival. Chang’s classification was used to grade the tumors. T stage did not have an impact on survival, but M stage did. No statistically significant difference in survival was found between the patients who had a total resection and those who had a subtotal resection. There was no difference in survival in terms of tumor location, hydrocephalus or ventriculoperitoneal shunt. Chemotherapy showed no survival benefit. The recurrence rate was 26%, and its timing followed Collin’s law. Recurrence led to death within 1–9 months. GH deficiency was diagnosed in 5 patients and hypothyroidism in 4 patients. The mean follow-up time was 4.4±3.7 years, with a range of 2.5 months to 16.5 years. Fourteen patients died, 5 were lost to follow-up, and 7 were transferred to adult care without persistent disease. Ten children are presently being followed up by the Neuro-oncology Clinic. Four children continue to be followed through psychology services. Our results are comparable to those in larger series, and are similar to those of the Montreal Children’s Hospital.

Predictors of Intellectual Function After a Unilateral Cortical Lesion: Study of 635 Patients From Infancy to Adulthood

This study investigated potential predictors of intellectual outcome in 417 children and 218 adults who had sustained a unilateral cortical lesion. Of these, 295 cases were collected from the scientific literature and 340 from medical records at seven hospitals in Canada. Different sets of predictors emerged for the Wechsler Verbal and Performance IQ values, accounting for differing variances (ie, 12.4% and 20.1%, respectively). The volume of the lesion was the factor that explained the most variance (ie, 4.95% and 11.7%, respectively). Age at lesion onset was significantly and positively correlated with verbal intelligence scores. This variable, considered independently or in interaction with other predictors, did not account for a large portion of the variance explained in intelligence. This refutes the commonly held notion that early onset of the insults results in a better prognosis. (J Child Neurol 2004; 19:935-943).

Serum Biomarkers Help Predict Attention Problems in Critically Ill Children With Traumatic Brain Injury

Objective: To evaluate the association between acute serum biomarkers, and the changes in attention at 1 year following traumatic brain injury. Design and Setting: A prospective observational and laboratory study conducted in PICUs at five Canadian children’s hospitals. Study Population and Measurements: Fifty-eight patients aged 5 to 17 years with traumatic brain injury were enrolled in the study. Nine brain-specific and inflammatory serum protein biomarkers were measured multiple times over the first week following injury. Attention was measured at “baseline” to represent pre-injury function and at 1 year following injury using the Conners Third Parent Rating Scale. Results: Compared with baseline, there were significantly more clinical symptoms of inattention at 1 year post injury. The Glasgow Coma Scale score, age at injury, baseline levels of inattention, and highest levels of serum biomarkers were used to estimate the probability of developing inattention. These independent variables were first evaluated individually followed by combinations of the best predictors using area under the receiver operating characteristic curve analyses. A combination of high baseline levels of inattention and high serum levels of the biomarker neuron-specific enolase was the best predictor for inattention. Glasgow Coma Scale and age at injury were not associated with inattention at 1 year post injury. Conclusions: Combining baseline assessment of attention with measurement of serum biomarkers shows promise as reliable, early predictors of long-term attention after childhood traumatic brain injury.

ASQ3 and/or the Bayley-III to support clinicians' decision making

Background Appropriate tools are essential to support a clinician’s decision to refer very preterm infants to developmental resources. Streamlining the use of developmental assessment or screening tools to make clinical decisions offers an alternative methodology to help to choose the most effective way to assess this very high-risk population. Objective To examine the influence of the Ages and Stages Questionnaire-3rd edition (ASQ3) and the Bayley Scales of Infant Development-3rd edition (Bayley-III) scores within a clinically-based decision-making process. Methods This retrospective cohort study includes children born at less than 29 weeks gestation who had completed both psychologist-administered Bayley-III and physician-observed ASQ3 assessments at 18 months corrected age. Theoretical referral decisions (TRDs) based on each assessment results were formulated, using cut-off scores between the lower first and second standard deviation values and below the lower second standard deviation values. TRDs to refer to developmental resources were evaluated in light of the multidisciplinary team’s actual final integrated decisions (FID). Results Complete data was available for 67 children. The ASQ3 and the Bayley-III had similar predictive value for the FID, with comparable kappa values. Comparisons of the physicians’ and psychologists’ TRDs with the FIDs demonstrated that the ASQ3 in conjunction with the medical and socio-familial findings predicted 93% of referral decisions. Conclusion Taking into consideration potential methodological biases, the results suggest that either ASQ3 or Bayley-III, along with socio-environmental, medical and neurological assessment, are sufficient to guide the majority of clinicians’ decisions regarding referral for specialty services. This retrospective study suggests that the physician-supervised ASQ3 may be sufficient to assess children who had been extremely preterm infants for referral purposes. The findings need to be confirmed in a larger, well-designed prospective study to minimize and account for potential sources of bias.