Does Early Age at Brain Insult Predict Worse Outcome? Neuropsychological Implications

Vicki Anderson, PhD; Rani Jacobs, PhD; Megan Spencer-Smith, PhD; Lee Coleman, MD; Peter Anderson, PhD; Jackie Williams, PhD; Mardee Greenham, BA (Hons); Rick Leventer, PhD

Disclosures

J Pediatr Psychol. 2010;35(7):716-727. 

In This Article

Methods

Participants

The sample comprised 164 children, including 92 (56.1%) males, aged between 10 and 16 years at recruitment (M = 13.07, SD = 1.88), with a history of EBI. Participants were ascertained between 2005 and 2007, through the Royal Children's Hospital, Melbourne. Eligible children were identified via hospital records and consecutive referrals to neuroscience outpatient clinics.

Inclusion criteria were: (a) aged 10–16 years at assessment; (b) evidence of focal brain pathology on MRI scan; and (c) brain insult at least 12 months prior to assessment, to allow for stabilization of recovery processes. Exclusion criteria were: (i) evidence of diffuse pathology (e.g., traumatic brain injury, cranial irradiation, hypoxia) on MRI scan; and (ii) non-English speaking. Eleven children were excluded based on study criteria. Approaches were made to 215 families, with 51 declining to participate (77% participation rate) due to time burden (n = 18), lack of interest (n = 29), or distance (n = 3). Table I provides demographic information on the sample.

The sample was divided into six "age at lesion" (AL) groups: (a) Congenital (CON) (n = 38): EBI during 1st and 2nd trimester; (b) Perinatal (PERI) (n = 33), EBI within the third trimester to 1 month postnatal; (c) Infancy (INF) (n = 23): EBI 2 months to 2 years postbirth; (d) Preschool (PRE) (n = 19): EBI 3–6 years of age; (e) Middle Childhood (MC) (n = 31): EBI 7–9 years of age; and (f) Late Childhood (LC) (n = 19): EBI after age 10.

Diagnoses were diverse, in order to ascertain children sustaining EBI across the developmental span of interest, and included focal pathologies stroke, contusions, penetrating head injury, tumor, dysplasia, cyst, and abscess. Details of the mechanism of insult and extent, laterality and region of lesion across the groups are provided in Table II.

Materials

Demographic Information Parents provided information on their child's medical and developmental history, parental occupation, and educational level. Socio-economic status (SES) was determined using Daniel's Scale of Occupational Prestige (Daniel, 1983), which rates parent occupation on a seven-point scale, where a high score reflects low SES.

MRI Scans (a) Acquisition: MRI scans were conducted, via standard protocol, as part of routine clinical practice prior to recruitment. For those who had not undergone scanning, or whose scans were unavailable, scans were conducted simultaneously with neurobehavioral evaluation. All scans were conducted on a 1.5 Tesla scanner, and axial and coronal slices were obtained. (b) Coding protocol: A coding protocol developed by Leventer and colleagues (1999) was employed to describe brain insult characteristics including: brain regions affected (lobes, subcortical structures), laterality (left, right, bilateral), extent of insult (focal, multifocal), and volume of brain affected (number of regions). Scans were coded simultaneously by an experienced pediatric neuroradiologist (LC) and neuropsychologist (MSS) who were blind to group membership. A randomly selected subset of 10 scans was re-coded independently by LC and MSS, with inter-rater reliability of.97.

Brain InsultTiming of brain insult was determined from a combination of MRI, brain biopsy, and medical record (clinical history, medical investigations). For pre- and perinatal insults this information was reviewed by an experienced paediatric neurologist (R.L.) and a neuropsychologist (M.S.S.), and rated according to the coding established by Leventer et al. (1999). Ten random cases were double-rated, with 100% consistency. Mechanism of insult was coded as: developmental, infective, ischemic, neuroplastic, or traumatic. Presence of seizure history and neurological abnormalities were recorded.

Neurobehavioral Measures Measures were selected to tap major neurobehavioral domains. This broad ranging approach was chosen in order to compare outcomes across domains, which are documented to emerge at different stages through childhood (e.g., language emerges in infancy, while executive skills emerge in later childhood). Criteria for test selection included: (a) robust normative data and psychometric properties; (b) appropriate across the age range under study. Unless otherwise specified, variables employed in analyses were scaled scores (M = 10, SD = 3).

  1. Intelligence: The four-subtest version of the Wechsler Abbreviated Intelligence Scale (WASI; Wechsler, 1999) was administered. Scores derived were Verbal (VIQ), Performance (PIQ) and Full Scale Intelligence Quotients (FSIQ) (M = 100, SD = 15).

  2. Language: (a) Vocabulary (VOC) and Similarities (SIM) subtests from WASI (Wechsler, 1999): T-scores (M = 50, SD = 10); (b) Peabody Picture Vocabulary Test – III (PPVT-III; Dunn & Dunn, 1997): stanine score (M = 5, SD = 2); and (c) Rapid Automatized Naming completion time (RAN: Clinical Evaluation of Language Function – 4: CELF 4; Semel, Wiig, & Secord, 2003): raw scores.

  3. Visuospatial skills: (a) Block Design (BD) and Matrix Reasoning (MR) subtests from WASI (Wechsler, 1999): T-scores (M = 50, SD = 10); (b) Rey Figure (REY; Rey, 1941); Copy Accuracy (REYACC): raw scores; and (c) Trail Making Test: Visual Scanning (TMT:VS): [Delis–Kaplan Executive Function System (D-KEFS); Delis, Kaplan, & Kramer, 2001].

  4. Attention: (a) Letter Number Sequencing [LNS: Wechsler Intelligence Scale for Children-IV (WISC-IV); Wechsler, 2003]; (b) Sky Search: time per target (SS:TPT; TEA-Ch; Manly et al., 1999): (c) Score: total correct (SCORE:TOT; TEA-Ch; Manly et al., 1999): (d) Sky Search Dual Task: decrement (SSDT:DEC; TEA-Ch; Manly et al., 1999): and (e) Creature Counting: total correct (CC:TOT; TEA-Ch; Manly et al., 1999).

  5. Memory: (a) California Verbal Learning Test (Delis, Kramer, Kaplan, & Ober, 1991): List A, Trials 1–5 (CVLT:TOT): T-score (M = 50, SD = 10), Long delay free (CVLT:DFR) and cued recall (CVLT:DCR): (M = 0, SD = 1); (b) Faces [Children's Memory Scale (CMS)] (Cohen, 1997), immediate (FACE:IMM) and delayed, (FACE:DEL) recall; and (c) Rey Complex Figure: (Rey, 1941): Recall (REYREC) and recall savings (REYSAV): raw scores.

  6. Executive function: (a) Verbal Fluency: Total correct (FAS:TOT: D-KEFS; Delis et al., 2001); (b) Tower Test: Total Achievement (TT:TA; D-KEFS; Delis et al., 2001); (c) CWI: Inhibition/Switching (CWI:I/S; D-KEFS; Delis et al., 2001); and (d) TMT: Number-letter switching versus combined number sequencing and letter sequencing (TMT:COM; D-KEFS; Delis et al., 2001).

  7. Processing speed: (a) SS Motor Control (SSM: TEA-Ch; Manly et al., 1999): time taken: raw score; (b) Color Word Interference: Naming + reading time (CWI:NRT: (D-KEFS); Delis et al., 2001); and (c) TMT motor speed [TMT:PS: (D-KEFS); Delis et al., 2001].

Procedure

This study was approved by the Human Research Ethics Committee, Royal Children's Hospital, Melbourne, Australia. Eligible children were identified via medical records, neuroradiology meetings or outpatient clinics. Families were contacted to ascertain their willingness to participate in the study and then mailed details of the study. Participating families were seen as outpatients, with a small number of children assessed at home or school. Informed consent was obtained from each child's parent/guardian at the time of assessment. Children were assessed individually, by a trained psychologist. Tests were administered in fixed order. Testers were blind to group membership. Assessments lasted ~2 hrs.

Statistical Analysis

Quantitative analyses were conducted using SPSS (version 14.0).

Initial analyses (ANOVA, Chi-squared) focused on determining presence of any group differences on descriptive demographic (SES, age at test, handedness) and lesion variables (age at diagnosis, time since diagnosis, seizures, mechanism, region, and extent of insult) which might contribute to group differences on neurobehavioral measures.

To address our first prediction, that children with EBI would perform more poorly than expected across all neurobehavioral domains, the total sample was compared to published test norms, using single sample t-tests. Alpha levels were adjusted using Holm's sequentially rejective Bonferroni procedure (Holm, 1977). For hypothesis 2, that age at brain insult would have long-term implications for neurobehavioral outcomes, multivariate planned contrasts were conducted for the language, visuo-spatial, attention and executive function domains, and MANOVA was used as for the information processing and memory domains. Specifically, a single contrast was conducted in both the language and visuo-spatial domains, comparing children with EBI before or at age 2 to those with EBI after age 2. For the attention and executive function domains, three contrasts were conducted: (a) children with EBI before or at age 2 versus children with EBI at age 3–6 years; (b) children with EBI before or at age 2 versus children with EBI at or after age 7; and (c) children with EBI at age 3–6 years versus children with EBI at or after age 7 years. Where domains included measures that employed raw scores, age at testing was included as a covariate. Similarly, the presence of seizures was included as a covariate where appropriate. Univariate analyses for both the planned contrast and MANOVA analyses employed Holm's procedure for adjusting alpha levels, and effect size was determined by η2 .

For neurobehavioral measures, some children were unable to complete some measures due to low functioning. In these instances, if test means and standard deviations were available, missing data were recoded conservatively to 2 SD below the test mean. Where raw scores were used and means were not available, data were not recoded. Data missing for other reasons (e.g., failure to return a questionnaire) were not recoded.

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