Greta N. Wilkening

Health status in 52 long-term survivors of pediatric brain tumors.

The percentage of children who survive childhood brain tumors is increasing. A number have neurological and other sequelae which impact on the quality of their survival. We reviewed long-term survivors using a standardized health status instrument. The mothers of 52 survivors of brain tumors were surveyed. Eight different aspects (attributes) of health status were scored. The first 6 of these attributes were scored in a health status index (HSI) developed at McMaster University. Subgroup analysis was performed. Limitation in the quality of life was found in one of the 8 attributes in all but 2 of the subjects. The health status index (HSI) score using the first 6 attributes of this survey had a median of 0.73 (range 0.16–1.00). This score is lower than that found in previously surveyed survivors of leukemia or other childhood cancers. Examination of age at diagnosis, extent of surgery, sex and therapeutic modalities used showed no correlation with HSI score. Those with supratentorial astrocytomas had a lower HSI score (0.65) than those with infratentorial astrocytomas (0.85) (p=0.05). Children with craniopharyngiomas had a poor score (0.64). This survey shows that the survivors of brain tumors have an appreciable burden of morbidity. Most have deficits in health status that affect many areas of their lives. Apart from site of the primary tumor, there was little correlation between subgroups studied and health status. The health status of children who survive brain tumors is lower than that of survivors of other childhood malignancies.

Neurobehavioral Outcome in Pediatric Craniopharyngioma

Neurobehavioral dysfunction occurs in children with craniopharyngioma, both before and after treatment, and its impact on outcome may not be fully appreciated. Also unclear is whether neurobehavioral outcome relates more to tumor location or surgical factors. We reviewed the records of 20 children with craniopharyngioma who were seen between 1983 and 1995. All children had subfrontal craniotomy and either partial (14 children) or gross total (6 children) resection of their tumors. In addition to traditional neuropsychological testing, we assessed social behavior and school performance using standardized ratings based on family interviews and school records. Over a mean follow-up period of 38 months, only 3 of 20 children had a good outcome in all three categories, and 12 of 20 had moderate or severe impairment in at least one category. Outcome did not differ between those who had partial and those with gross total resection. We conclude that neurobehavioral disorders are common and cause important morbidity in children after treatment for craniopharyngioma. To evaluate these impairments in future outcome studies, standard neuropsychological testing should be supplemented by specific behavioral assessments to capture the full range of neurobehavioral disability. In this series, partial versus gross total resection did not influence outcome, implying that tumor location in diencephalic and limbic regions is a more important factor.

Late effects of total body irradiation and hematopoietic stem cell transplant in children under 3 years of age

Total body irradiation (TBI) is an important component of hematopoietic stem cell transplant (SCT) for pediatric malignancies. With increasing survival rates, late effects of SCT become more important. Younger children may be at particular risk of late effects of radiation and SCT.

Biomarkers of Hypercoagulability and Inflammation in Childhood-Onset Arterial Ischemic Stroke

OBJECTIVE To test the hypothesis that acute elevations of biomarkers of hypercoagulability and inflammation are common in children with arterial ischemic stroke (AIS), particularly among etiologic subtypes that carry an increased risk of recurrent stroke. STUDY DESIGN In this prospective/retrospective institutional-based cohort study of acute childhood-onset AIS (n = 50) conducted between 2005 and 2009, D-dimer, factor VIII (FVIII) activity, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were serially evaluated at the time of clinical blood sampling. Patients were classified by stroke subtype as cardioembolic, moyamoya, non-moyamoya arteriopathy, or other. RESULTS Both D-dimer and CRP were frequently elevated in acute childhood-onset AIS and exhibited a decreasing trend with time. Acute D-dimer levels were significantly higher in cardioembolic AIS compared with noncardioembolic AIS (median, 2.04 microg/mL [range 0.54-4.54 microg/mL] vs 0.32 microg/mL [0.22-3.18 microg/mL]; P = .002). At an optimal threshold of > or = 0.50 microg/mL, the sensitivity and specificity of D-dimer for cardioembolic subtype were 78% and 79%, respectively. CONCLUSIONS Our findings identify D-dimer and CRP as candidate biomarkers for etiology and prognosis in childhood-onset AIS. Further studies should investigate the role of these and other biomarkers of hypercoagulability and inflammation in childhood-onset AIS.

The Luria‐Nebraska Neuropsychological battery—children's revision: Theory and current research findings

The Luria‐Nebraska Neuropsychological Battery (LNNB) has gained an unusual amount of acceptance for a new psychological instrument, probably because of its derivation from the neuropsychological theories of Aleksandr R. Luria. Some of the basic concepts of Lurias theories are explained in this article, and some of the advantages and disadvantages of standardized neuropsychological batteries are discussed. The derivation of the Childrens Revision of the LNNB is briefly described and a review is presented of current research utilizing the battery. It is concluded that initial research using the Childrens LNNB is optimistic, but, like any psychological instrument, extensive research is needed in order to prove its worth, and the authors encourage continued investigation.

The Luria-Nebraska Neuropsychological Battery-Children's Revision: Validation with Brain-Damaged and Normal Children

This paper discusses briefly the development and rationale behind the Luria-Nebraska Neuropsychological Battery-Childrens Revision. Three investigations are discussed: (a) the development of normative data on a group of 125 normal children between the ages of 96 and 155 months, (b) development of the critical level formula for determining the upper bounds for normal performance given a childs age, and (c) a validation of the ability of the battery to discriminate between normal and brain-injured children selected as a separate sample from that used in the initial investigations. In the third study, a MANOVA as well as subsequent individual t tests indicated highly significant group differences. Counting scores above the patients critical level (as determined from the formula designed in the second investigation) resulted in correct classification of 89% of the normal children and 79% of the brain-injured children. Methods of interpreting the battery and limitations of the current study are discussed.

Potential for Improved Intelligence Quotient Using Volumetric Modulated Arc Therapy Compared With Conventional 3-Dimensional Conformal Radiation for Whole-Ventricular Radiation in Children

PURPOSE To compare volumetric modulated arc therapy (VMAT) with 3-dimensional conformal radiation therapy (3D-CRT) in the treatment of localized intracranial germinoma. We modeled the effect of the dosimetric differences on intelligence quotient (IQ). METHOD AND MATERIALS Ten children with intracranial germinomas were used for planning. The prescription doses were 23.4 Gy to the ventricles followed by 21.6 Gy to the tumor located in the pineal region. For each child, a 3D-CRT and full arc VMAT was generated. Coverage of the target was assessed by computing a conformity index and heterogeneity index. We also generated VMAT plans with explicit temporal lobe sparing and with smaller ventricular margin expansions. Mean dose to the temporal lobe was used to estimate IQ 5 years after completion of radiation, using a patient age of 10 years. RESULTS Compared with the 3D-CRT plan, VMAT improved conformality (conformity index 1.10 vs 1.85), with slightly higher heterogeneity (heterogeneity index 1.09 vs 1.06). The averaged mean doses for left and right temporal lobes were 31.3 and 31.7 Gy, respectively, for VMAT plans and 37.7 and 37.6 Gy for 3D-CRT plans. This difference in mean temporal lobe dose resulted in an estimated IQ difference of 3.1 points at 5 years after radiation therapy. When the temporal lobes were explicitly included in the VMAT optimization, the mean temporal lobe dose was reduced 5.6-5.7 Gy, resulting in an estimated IQ difference of an additional 3 points. Reducing the ventricular margin from 1.5 cm to 0.5 cm decreased mean temporal lobe dose 11.4-13.1 Gy, corresponding to an estimated increase in IQ of 7 points. CONCLUSION For treatment of children with intracranial pure germinomas, VMAT compared with 3D-CRT provides increased conformality and reduces doses to normal tissue. This may result in improvements in IQ in these children.

Arteriopathy, D-Dimer, and Risk of Poor Neurologic Outcome in Childhood-Onset Arterial Ischemic Stroke

OBJECTIVE To assess whether acute findings of cerebral arteriopathy, large infarct, and acutely elevated plasma D-dimer levels are independently prognostic of poor long-term neurologic outcome as measured at ≥ 1 year post-event in children with arterial ischemic stroke (AIS). STUDY DESIGN Sixty-one patients with childhood-onset (ie, >28 days of life) AIS were enrolled in a single-institution cohort study at Childrens Hospital Colorado between February 2006 and June 2011. Data on demographic and diagnostic characteristics, antithrombotic treatments, and outcomes were systematically collected. RESULTS Cerebral arteriopathy and D-dimer levels >500 ng/mL (a measure of coagulation activation) were identified acutely in 41% and 31% of the cohort, respectively. Anticoagulation was administered in the acute period post-event in 40% of the children, in the subacute period in 43%, and in the chronic period in 28%. When not receiving anticoagulation, patients were routinely treated with aspirin 2-5 mg/kg once daily for a minimum of 1 year. Death, major bleeding (including intracranial hemorrhage), and recurrent AIS were infrequent. The Pediatric Stroke Outcome Measure at 1 year demonstrated poor outcome in 54% of the children. Acute cerebral arteriopathy and elevated D-dimer level were identified as putative prognostic factors for poor outcome; after adjustment for D-dimer, arteriopathy was an independent prognostic indicator (OR, 19.0; 95% CI, 1.6-229.8; P = .02). CONCLUSION Arteriopathy and coagulation activation are highly prevalent in the acute period of childhood AIS. Although recurrent AIS and intracranial hemorrhage were infrequent in our cohort, one-half of children experienced a poor neurologic outcome at 1 year, the risk of which was increased by acute arteriopathy. Substantiation of these findings in multi-institutional cohort studies is warranted, toward risk stratification in childhood-onset AIS.

Development of Factor Scales for the Luria-Nebraska Neuropsychological Battery-Children's Revision

Factor scales to be used in the interpretation of the Luria-Nebraska Neuropsychological Battery-Childrens Revision (LNNB-CR) were derived. The protocols from 719 children (240 normal, 253 brain impaired, 32 suspected brain impaired, 39 learning disabled, 5 leukemic, and 150 psychiatric) were utilized. Factors from overall and individual scale analyses were compared, and only those demonstrating adequate internal consistency and reasonable independence of the clinical scales were retained. This resulted in a final set of 11 internally consistent, largely nonredundant factors. Suggestions for factor scale interpretation and comparison of the LNNB-CR factors with those found on other measures were made.

Relationships Between the Booklet Category Test and the Wisconsin Card Sorting Test

This study compares total errors on the Booklet Form of the Category Test (DeFilippis, McCampbell & Rogers, 1979) with several scores of the Wisconsin Card Sorting Test (Heaton, 1981). In a heterogeneous sample of 30 neurologically impaired patients and 31 normal individuals the two tests exhibited a maximum correlation of 0.52 when partialing out the effects of age and education. In addition, this study suggests that the two exhibit similar overall diagnostic hit rates; however, they differ in false negatives and false positives. These results bring into question the assumption that these two neuropsychological tests are interchangeable. A need to recognize the nature of the differences between the tests in their clinical applications and in future research is discussed.