Postshunt lateral ventricular volume, white matter integrity, and intellectual outcomes in spina bifida and hydrocephalus.

Williams VJ, Juranek J, Stuebing KK, Cirino PT, Dennis M, Bowman RM, Blaser S, Kramer LA, Fletcher JM. (2015) Postshunt lateral ventricular volume, white matter integrity, and intellectual outcomes in spina bifida and hydrocephalus.

J Neurosurg Pediatr. 2015 Apr;15(4):410-9. doi: 10.3171/2014.10.PEDS13644

Abstract

OBJECT No previous reports exist that have evaluated the relationships of white matter (WM) integrity with the number of shunt revisions, ventricular volume after shunting, and cognition in medically stable children who have spina bifida and hydrocephalus (SBH). The authors hypothesized that enlarged ventricles and a greater number of shunt revisions decrease WM integrity in children. METHODS In total, 80 children (mean age 13.7 years) who had SBH underwent MRI and IQ testing. Probabilistic diffusion tractography was performed to determine mean diffusion tensor imaging (DTI) metrics along the frontal and parietal tectocortical pathways. The DTI metrics were evaluated for significant correlation with a composite IQ measure and with the total number of shunt revisions and the total lateral ventricular volume obtained through semiautomated parcellation of T1-weighted MRI scans. RESULTS An enlargement in total lateral ventricle volume and an increase in the number of shunt revisions were both associated with higher fractional anisotropy (FA) and with lower radial diffusivity (RD) along both frontal and parietal tectocortical pathways. Children who had not undergone a shunt revision had on average a greater lateral ventricle volume and higher FA and lower RD along frontal and parietal pathways than those who had undergone multiple shunt revisions. The mean DTI metrics along parietal pathways predicted IQ scores, but intellectual ability was not significantly correlated with ventricular volume or with the number of lifetime shunt revisions. CONCLUSIONS Significant changes in DTI metrics were observed as a function of ventricular volume. An increased lateral ventricle volume was associated with elevated FA and decreased RD. Given that the participants were medically stable at the time of the MRI examination, the results suggested that those who have enlarged ventricles show a DTI pattern consistent with axonal compression due to increased intracranial pressure (ICP) in attenuated hydrocephalus. Although limited by a cross-sectional design, the study's findings suggest that DTI metrics may serve as sensitive indicators for chronic, mild hydrocephalus in the absence of overt clinical symptoms due to increased ICP. Having enlarged ventricles and undergoing multiple shunt revisions did not affect intellectual ability in children with SBH.

Why IQ is not a covariate in cognitive studies of neurodevelopmental disorders.

Dennis M, Francis DJ, Cirino PT, Schachar R, Barnes MA, Fletcher JM. Why IQ is not a covariate in cognitive studies of neurodevelopmental disorders. Journal of the International Neuropsychological Society. 2009 May;15(3):331-43.

Department of Psychology, The Hospital for Sick Children, Toronto, Ontario, Canada. maureen.dennis@sickkids.ca

IQ scores are volatile indices of global functional outcome, the final common path of an individual's genes, biology, cognition, education, and experiences. In studying neurocognitive outcomes in children with neurodevelopmental disorders, it is commonly assumed that IQ can and should be partialed out of statistical relations or used as a covariate for specific measures of cognitive outcome. We propose that it is misguided and generally unjustified to attempt to control for IQ differences by matching procedures or, more commonly, by using IQ scores as covariates. We offer logical, statistical, and methodological arguments, with examples from three neurodevelopmental disorders (spina bifida meningomyelocele, learning disabilities, and attention deficit hyperactivity disorder) that: (1) a historical reification of general intelligence, g, as a causal construct that measures aptitude and potential rather than achievement and performance has fostered the idea that IQ has special status and that in studying neurocognitive function in neurodevelopmental disorders; (2) IQ does not meet the requirements for a covariate; and (3) using IQ as a matching variable or covariate has produced overcorrected, anomalous, and counterintuitive findings about neurocognitive function.

PMID: 19402919

Quantitative diffusion tensor imaging and intellectual outcomes in spina bifida: laboratory investigation

Hasan KM, Sankar A, Halphen C, Kramer LA, Ewing-Cobbs L, Dennis M, Fletcher JM.
Quantitative diffusion tensor imaging and intellectual outcomes in spina bifida: laboratory investigation.
Journal of Neurosurgery: Pediatrics. 2008 Jul;2(1):75-82.

OBJECT: Patients with spina bifida (SB) have variable intellectual outcomes. The authors used diffusion tensor (DT) imaging to quantify whole-brain volumes of gray matter, white matter, and cerebrospinal fluid (CSF), and perform regional quantitative microstructural assessments of gray matter nuclei and white matter tracts in relation to intellectual outcomes in patients with SB.

METHODS: Twenty-nine children with myelomeningoceles and 20 age- and sex-matched children with normal neural tube development underwent MR imaging with DT image acquisition and assessments of intelligence. The DT imaging-derived metrics were the fractional anisotropy (FA), axial (parallel), and transverse (perpendicular) diffusivities. These metrics were also used to segment the brain into white matter, gray matter, and CSF. A region-of-interest analysis was conducted of the white and gray matter structures implicated in hydrocephalus.

RESULTS: The amount of whole-brain gray matter was decreased in patients with SB, with a corresponding increase in CSF (p < 0.0001). Regional transverse diffusivity in the caudate nucleus was decreased (p < 0.0001), and the corresponding FA was increased (p < 0.0001), suggesting reduced dendritic branching and connectivity. Fractional anisotropy in the posterior limb of the internal capsule increased in the myelomeningocele group (p = 0.02), suggesting elimination of some divergent fascicles; in contrast, the FA in several white matter structures (such as the corpus callosum genu [p < 0.001] and arcuate fasciculus) was reduced, suggesting disruption of myelination. Diffusion tensor imaging-metrics involving gray matter volume and the caudate nucleus, but not other structures, predicted variations in IQ (r = 0.37-0.50; p < 0.05).

CONCLUSIONS: Diffusion tensor imaging-derived metrics provide noninvasive neuronal surrogate markers of the pathogenesis of SB and predict variations in general intellectual outcomes in children with this condition.


PMID: 18590401

Intelligence quotient in children with meningomyeloceles: a case-control study.

Nejat F, Kazmi SS, Habibi Z, Tajik P, Shahrivar Z. Intelligence quotient in children with meningomyeloceles: a case-control study. Journal of Neurosurgery. 2007 Feb;106(2 Suppl):106-10.

OBJECT: Meningomyelocele (MMC) is a common central nervous system birth defect. As one of many problems facing patients with MMC, learning disabilities are often overlooked. The aim of this study was to evaluate IQs in a group of children with MMCs and determine if a correlation exists between intelligence level and the presence of an MMC and/or its complications.

METHODS: A case-control study was conducted at the Children's Hospital Medical Center in Tehran, Iran, from December 2004 through December 2005. The patient group included 50 children with MMC from 5 to 12 years of age who were referred to the authors' institution for treatment of complications or for follow up after surgery for MMC closure. The patient group was individually matched for age and sex with a control group of 50 children referred to the hospital for other reasons and who did not have MMC or other neurological abnormalities. The IQs in all children in this study were evaluated using the Ravens Progressive Matrices test. The children in both groups were similar in the socioeconomic status of the family (p = 0.347) and educational status of the father (p = 0.117) and mother (p = 0.439). Patient age at the time of surgery for MMC closure varied from 1 day to 96 months (mean 4.1 months). Only 20% of the patients with MMC could walk with a normal gait. Forty-six percent of the patients had undergone placement of a ventriculoperitoneal shunt, and half of these patients experienced shunt-related complications; 72% of the children in the patient group were completely incontinent for both urine and feces. The IQ results obtained in the patient group ranged from 73 to 134 with a mean (+/- standard deviation) of 96.62 +/- 13.01. In the control group the IQ range was 70 to 128, and the mean was 104.82 +/- 12.30. Compared with the control group there was a statistically significant correlation between having an MMC and having a lower IQ (p < 0.001, paired t-test).

CONCLUSIONS: Although the average IQ in the patient group was significantly lower than that in the control group, it is important to note that all children in the patient group had an average or above-average IQ. In contrast with the results reported in other studies, earlier repair of the MMC, the presence of a shunt or shunt-related complications, walking difficulty, and the spinal level of the lesion did not correlate significantly with IQs. Therefore, the lower IQ and reduced cognitive levels noted in these patients result from the disease process itself and not from the associated complications.

PMID: 17330535

Spinal lesion level in spina bifida: a source of neural and cognitive heterogeneity.

Fletcher JM, Copeland K, Frederick JA, Blaser SE, Kramer LA, Northrup H, Hannay HJ, Brandt ME, Francis DJ, Villarreal G, Drake JM, Laurent JP, Townsend I, Inwood S, Boudousquie A, Dennis M. Spinal lesion level in spina bifida: a source of neural and cognitive heterogeneity. J Neurosurg. 2005 Apr;102(3 Suppl):268-79.

OBJECT: The aim of this study was to evaluate whether the level of a spinal lesion is associated with variations in anomalous brain development and neurobehavioral outcomes in children suffering from the meningomyelocele form of spina bifida and hydrocephalus (SBM-H).

METHODS: Two hundred sixty-eight children with SBM-H were divided into upper (T-12 and above; 82 patients) and lower (L-1 and below; 186 patients) lesion-level groups. Magnetic resonance images were qualitatively coded by radiologists and quantitatively segmented for cerebrum and cerebellum volumes. Psychometric assessments of handedness, intelligence, academic skills, and adaptive behavior were compared between lesion-level groups and also used to determine the number of children who met research-based criteria for mental retardation, attention deficit hyperactivity disorder, and learning disabilities. The magnetic resonance images obtained in children with upper-level spinal lesions demonstrated more qualitative abnormalities in the midbrain and tectum, pons, and splenium, although not in the cerebellum, compared with images obtained in children with lower-level spinal lesions. Upper-level lesions were also associated with reductions in cerebrum and cerebellum volumes, lower scores on measures of intelligence, academic skills, and adaptive behavior, and with a higher frequency of individuals meeting the criteria for mental retardation. Hispanic children (who were also more economically disadvantaged) were more likely to have upper-level lesions and poorer neurobehavioral outcomes, but lesion-level effects were generally independent of ethnicity.

CONCLUSIONS: A higher level of spinal lesion in SBM-H is a marker for more severe anomalous brain development, which is in turn associated with poorer neurobehavioral outcomes in a wide variety of domains that determine levels of independent functioning for these children at home and school.

PMID: 15881750

Regional brain tissue composition in children with hydrocephalus. Relationships with cognitive development.

Fletcher JM, McCauley SR, Brandt ME, Bohan TP, Kramer LA, Francis DJ, Thorstad K, Brookshire BL. Regional brain tissue composition in children with hydrocephalus. Relationships with cognitive development.
Archives Neurology. 1996 Jun;53(6):549-57.

OBJECTIVE: To determine whether children with shunted hydrocephalus show variations in regional brain tissue composition that relate to cognitive functions.

DESIGN: Nonequivalent control group.

PATIENTS AND METHODS: Magnetic resonance imaging (MRI) and cognitive skills assessments were obtained on 28 children, 6 to 9 years of age, with shunted hydrocephalus and 13 normal control subjects comparable in age, gender, ethnicity, and socioeconomic status. Three consecutive MRI slices below the vertex were segmented using a fuzzy clustering algorithm to separate pixels into gray matter, white matter, and cerebrospinal fluid (CSF) in quadrants representing left and right anterior and posterior brain regions. The cognitive skills assessments included the Wechsler Intelligence Scale for Children-Revised verbal and performance IQ scores, neuropsychological composites of language and visuospatial skills, a measure of visuomotor dexterity, and 2 measures of problem-solving abilities. The MRI data were analyzed in a group x tissue x hemisphere x region analysis of variance. Spearman rho correlations were computed within the hydrocephalus group between the MRI and cognitive measures.

RESULTS: Children with hydrocephalus showed reductions in overall gray matter percentages and corresponding increased CSF percentages that were more pronounced in posterior than anterior regions of both hemispheres. White matter percentages were reduced in children with hydrocephalus only in the left posterior quadrant. Correlations of posterior, but not anterior, CSF and gray matter percentages were significant with verbal and performance IQ scores and language, visuospatial, and visuomotor dexterity skills, but not with problem-solving abilities. Children with hydrocephalus who had proportionately greater posterior than anterior CSF percentages had significantly poorer visuomotor dexterity and visuospatial skills than did hydrocephalic children with proportionate CSF percentages.

CONCLUSION: Regional variations in brain tissue composition in children with shunted hydrocephalus correlate with a variety of cognitive and visuomotor functions.

MRI morphometric study and correlation with cognitive functions in young adults shunted for congenital hydrocephalus related to spina bifida.

Hommet C, Cottier JP, Billard C, Perrier D, Gillet P, De Toffol B, Sirinelli D, Bertrand P, Autret A. MRI morphometric study and correlation with cognitive functions in young adults shunted for congenital hydrocephalus related to spina bifida. European Neurology. 2002;47(3):169-74. Links

We studied the morphometric MRI findings and their correlation with cognitive functions in a population of 10 young adults shunted for congenital hydrocephalus related to spina bifida. Morphometric MRI analysis included measurement of the ventricular dilatation index, frontal and occipital parenchymal thickness and the size of the corpus callosum. The neuropsychological status was evaluated, notably to look for a discrepancy between verbal and performance skills, a finding which has previously been described in hydrocephalic children. We also investigated whether there was a correlation between cognitive function and cerebral morphometric indexes. In each case, MRI demonstrated the structural changes associated with the Chiari II malformation. The size of the lateral ventricles varied, ranging from important dilatation to small ventricles. Six patients had only partial development of the corpus callosum. All patients had a normal global IQ. In our population of young adults, we did not observe any discrepancy between verbal and visuospatial performances as has been described in children with hydrocephalus. We found no relationship between cognitive function and ventricle dilatation or parenchymal thickness or between the size of the corpus callosum and callosal transfer.

Arnold-Chiari-II malformation and cognitive functioning in spina bifida.

Vinck A, Maassen B, Mullaart R, Rotteveel J. Arnold-Chiari-II malformation and cognitive functioning in spina bifida. Journal of Neurology, Neurosurgery, and Psychiatry 2006 Sep;77(9):1083-6. Epub 2006 May 11.

Spina bifida is a multifaceted neurological condition with complex neuropsychological sequelae. The cognitive outcome in spina bifida has frequently been attributed to the severity of the hydrocephalus. However, because of complex neuropathology, the influence of hydrocephalus alone does not sufficiently explain the deficits in the cognitive profile in spina bifida. To date, little is known of the role of Arnold-Chiari-II malformation (ACM) in the cognitive profile of these patients. Aim of the current study is to delineate the specific contribution of the ACM in spina bifida by comparing children with ACM and those without ACM. 46 children between 6 and 15 years of age underwent a neuropsychological assessment covering intelligence and a wide range of cognitive functions, such as visuo-motor processing, attention, memory, word fluency and speed of information processing. Comparisons were made between patients with ACM (ACM+) and those without ACM (ACM-); all children with ACM+ also had hydrocephalus. Confounding effects of global cognitive impairment were excluded, such that groups were matched on verbal IQ. Because of complex neuropathology, which is inherent to spina bifida, the method applied was based on a comparison of cognitive profiles of the study group with profiles of patients with cerebellar damage and hydrocephalus found in the literature. Impaired visual analysis and synthesis, verbal memory, and verbal fluency, even after correction for global cognitive impairment, were observed in children with ACM. The hypothesis that in addition to impairment in visual analysis and synthesis, which are related to both hydrocephalus and ACM, specific deficiencies in verbal memory and fluency may be attributed to ACM is supported.

Functional outcome in young adults with spina bifida and hydrocephalus.

Hetherington R, Dennis M, Barnes M, Drake J, Gentili F.
Functional outcome in young adults with spina bifida and hydrocephalus.
Childs Nervous System. 2006 Feb;22(2):117-24. Epub 2005 Sep 17.

INTRODUCTION: Quality of life was studied in 31 adult survivors of spina bifida, each with Verbal or Performance IQ score over 70.

METHODS: Instruments measured physical and occupational function, cognitive/psychological function, somatic sensation, and social interaction in the context of the ability to live independently.

RESULTS: Domain group means except motor independence were in the average range (+/- 1 standard deviation). Variability within the group with respect to physical phenotype (high spinal lesions were associated with poorer motor independence) and medical history [a greater number of shunt revisions (> 4) were associated with poorer functional numeracy] was predictive of quality of life. Both spinal lesion level and number of shunt revisions influenced occupational status.

DISCUSSION: There was a relation between everyday mathematics, reading skills, and quality of life. The consequences of the physical, medical, and cognitive effects of spina bifida extend into young adulthood and have an impact on quality of life.