The cognitive phenotype of spina bifida meningomyelocele.

Dennis M, Barnes MA. (2010) The cognitive phenotype of spina bifida meningomyelocele. Dev Disabil Res Rev. 2010;16(1):31-9.

A cognitive phenotype is a product of both assets and deficits that specifies what individuals with spina bifida meningomyelocele (SBM) can and cannot do and why they can or cannot do it. In this article, we review the cognitive phenotype of SBM and describe the processing assets and deficits that cut within and across content domains, sensory modality, and material, including studies from our laboratory and other investigations. We discuss some implications of the SBM cognitive phenotype for assessment, rehabilitation, and research.

PMID: 20419769

Cognitive and functional outcome in spina bifida-Chiari II malformation.

Jenkinson MD, Campbell S, Hayhurst C, Clark S, Kandasamy J, Lee MK, Flynn A, Murphy P, Mallucci CL.
Cognitive and functional outcome in spina bifida-Chiari II malformation.
Childs Nerv Syst. 2010 Dec 31.


PURPOSE: The long-term outcome in spina bifida-Chiari II-hydrocephalus complex is poorly understood. Traditional neurosurgical outcome measures are crude. Neuropsychological testing is increasingly important in outcome assessment. We investigated the health, disability, lifestyle and cognitive function in adults who had myelomeningocoele closure at birth.

METHODS: Adult patients under routine follow-up were assessed in a joint neurosurgery/neuropsychology clinic. Patients completed lifestyle questionnaires, the hydrocephalus outcome questionnaire (HOQ) and underwent cognitive testing. Clinical variables including number of shunt revisions, shunt infection and surgical decompression of foramen magnum, which may influence outcome, were investigated.

RESULTS: Twenty-one adults with a median age of 35 years were investigated. All had treated hydrocephalus, and eight had foramen magnum decompression for headache or progressive brainstem symptoms with stabilisation of symptoms in seven and improvement in one. Only eight patients were living independently, five were in paid employment and five work voluntarily. HOQ scores for cognitive function were lower (0.56 ± 0.20; mean ± standard deviation (SD)) than those for physical (0.64 ± 0.15) and social-emotional (0.65 ± 0.17) health. Cognitive function varied across the cohort with attention most severely affected (73.9 ± 17.0; mean ± SD). Repeated episodes of shunt malfunction or foramen magnum decompression were not associated with a worse cognitive function.

CONCLUSIONS: Despite intervention in childhood and adequate cerebrospinal fluid diversion the prognosis for independent living into adulthood remains poor. All patients have elements of cognitive impairment. Structural brain abnormalities may be more important determinants of cognitive outcome than shunt malfunction.



PMID: 21193992

Cognitive functions in children with myelomeningocele without hydrocephalus

Lindquist B, Uvebrant P, Rehn E, Carlsson G. (2009) Cognitive functions in children with myelomeningocele without hydrocephalus. Child’s Nervous System. 2009 Aug;25(8):969-75.

OBJECTIVE: The aim of this study was to explore the separate effects of myelomeningocele (MMC) and hydrocephalus on intelligence and neuropsychological functions in a population-based series of children.

MATERIAL AND METHODS: Of the 69 children with MMC born in 1992-1999 in western Sweden, nine did not develop hydrocephalus. Eight of them participated in this study and were compared with age- and gender-matched children with MMC in combination with hydrocephalus and with controls.

RESULTS: Children with only MMC had an IQ of 103 compared with 75 in those with hydrocephalus added to the MMC and they had significantly better immediate and long-term memory and executive functions. When compared with controls, they had difficulty with learning and executive functions, but when the two children with an IQ of less than 70 were excluded, those with only MMC performed just as well as the controls.

CONCLUSION: Hydrocephalus rather than MMC in itself appeared to cause the cognitive deficits found in children with MMC.

PMID: 19263057

Prospective memory in adults with spina bifida

Dennis M, Nelson R, Jewell D, Fletcher JM. (2010) Prospective memory in adults with spina bifida. Child's Nervous System. 2010 Apr 15

INTRODUCTION: Individuals with neurodevelopmental disorders have been observed to show accelerated cognitive aging or even dementia as early as 30 and 40 years of age. Memory deficits are an important component of age-related cognitive loss.

METHODS: In this study, we investigated prospective memory, which is often impaired in aging, in a group of 32 adults with spina bifida meningomyelocele (SBM), including members of the oldest living cohort successfully treated with shunts to divert excess cerebrospinal fluid, ventriculomegaly, and hydrocephalus, who are now around 50 years of age. Seventeen typically developing adults provided a comparison group.

RESULTS: The SBM and comparison groups differed in the prospective memory total score as well as in both time-based and event-based subscores. Prospective memory was impaired in both older and younger individuals with SBM. However, the percentage of individuals with impaired or poor prospective memory was three times higher in the older SBM group than in the younger SBM group. The results are considered in relation to specific features of the complex brain reorganization in SBM.

PMID: 20393850

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

Motor profile and cognitive functioning in children with spina bifida.

Vinck A, Nijhuis-van der Sanden MW, Roeleveld NJ, Mullaart RA, Rotteveel JJ, Maassen BA. Motor profile and cognitive functioning in children with spina bifida.
European Journal of Pediatric Neurology. 2009 Feb 21. [Epub ahead of print]

Department of Medical Psychology, Radboud University Nijmegen Medical Centre, The Netherlands; Department of Paediatric Neurology, Radboud University Nijmegen Medical Centre, The Netherlands.

BACKGROUND: Spina bifida is a complex neuroembryological disorder resulting from incomplete closure of the posterior neural tube. Morbidity in the different fields of motor and cognitive neurodevelopment is variable in nature and severity, and often hard to predict.

AIMS: The current study investigates the relationship between cognitive functioning, fine motor performance and motor quality in children with spina bifida myelomeningocele (SBM) and SB-only, taking into consideration the cerebral malformations.

MATERIAL AND METHODS: Forty-one children were included (22 girls and 19 boys aged between 6 and 14 years, mean age 10;0 years) in the study. A comprehensive assessment was conducted of cognitive functioning and motor profile, including fine motor and visual-motor functioning, and motor quality. The performance outcomes were analyzed for the total group of children and separately for the nonretarded children (FSIQ>/=70, N=30) to eliminate the influence of global intellectual impairment.

RESULTS: Although the children with spina bifida showed increased incidence of cognitive and fine motor impairment, and impaired motor quality, after exclusion of the overall retarded children no associations were found between cognitive functioning and motor profile. In the comparison of SBM to SB-only specific differences were found for performance IQ, visual-motor functioning and motor quality, but not fine motor functioning.

CONCLUSION: Our findings underscore the role of cerebral malformation in spina bifida and its consequences for neuropsychological functioning. The complicated developmental interactions found strengthen the need for an individualized management of children with SB.

PMID: 19237302

Mental rotation ability of children with spina bifida: what influence does manual rotation training have

Wiedenbauer G, Jansen-Osmann P. Mental rotation ability of children with spina bifida: what influence does manual rotation training have? Developmental Neuropsychology. 2007;32(3):809-24.

We investigated the mental rotation ability of children with spina bifida, a malformation of the spinal cord due to a neural tube defect, and how it is influenced by a manual rotation training. In comparison to a healthy control group these children showed longer reaction times and a higher number of errors in a computer-based mental rotation test. Furthermore, a manual rotation training was applied. The spina bifida group benefited considerably from the manual rotation training. The training effect was not limited to stimuli learned in the training. While the children with spina bifida showed a lower speed of mental rotation than their healthy peers in the mental rotation pretest, the two groups did not differ in their mental rotation speed in the posttest.

PMID: 17956183

Cerebral white matter and cognition in hydrocephalic children

Fletcher JM, Bohan TP, Brandt ME, Brookshire BL, Beaver SR, Francis DJ, Davidson KC, Thompson NM, Miner ME. Cerebral white matter and cognition in hydrocephalic children. Archives of Neurology. 1992 Aug;49(8):818-24.

Although children with hydrocephalus frequently show poor development of nonverbal cognitive skills relative to verbal skills, little is known about the neuropathologic correlates of these discrepancies. In this study, cerebral white-matter structures and lateral ventricles were measured from the magnetic resonance images of age-matched children with meningomyelocele, meningocele, and aqueductal stenosis and normal subjects. The volume of each lateral ventricle and the cross-sectional area of the corpus callosum and internal capsules were correlated with concurrent measures of verbal and nonverbal cognitive skills. The corpus callosum in the meningomyelocele and aqueductal stenosis groups was smaller. The lateral ventricles were larger, and the internal capsules were smaller, in all patient groups than in normal subjects. There were no differences in the size of the centra semiovale. Although verbal and nonverbal measures correlated positively with the size of the corpus callosum, the correlation was higher for nonverbal measures. Nonverbal measures correlated with the right, but not the left, lateral ventricle and with the area of the right and left internal capsules. Verbal measures correlated with the left, but not right, lateral ventricle and with the left, but not right, internal capsule. These results show a relationship between the corpus callosum and cognitive skills that is also influenced by hydrocephalus-related changes in the lateral ventricles and other cerebral white-matter tracts.

PMID: 1524514

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 of 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.

PMID: 8660158

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 & 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.

PMID: 16690692

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

A model of neurocognitive function in spina bifida over the life span

Dennis M, Landry SH, Barnes M, Fletcher JM. A model of neurocognitive function in spina bifida over the life span. Journal of the International Neuropsychological Society. 2006 Mar;12(2):285-96. Review.

Spina bifida myelomeningocele (SBM), a neural tube defect that is the product of a complex pattern of gene-environment interactions, is associated with naturally occurring, systematic variability in the neural phenotype and in environmental factors that lead to systematic variability in the cognitive phenotype. We characterize the basis for variability in the cognitive phenotype of children with SBM with reference to a model of key biological, cognitive, and environmental events unfolding over the course of development from infancy to middle age. The cognitive phenotype is not domain-specific, but represents manifestations of unobservable constructs involving associative and assembled processing, the latter directly reflecting the impact of the neural phenotype on core deficits involving movement, timing, and attention orienting. The expression of the cognitive phenotype is variable, being moderated by features of the neural phenotype involving secondary CNS insults (such as hydrocephalus) that impair assembled processing, as well as by environmental factors (such as poverty, parenting, and education) that impair associative processing. The preservation of strengths in associative processing depends in part on the severity of the CNS deficits in SBM and the impact of the environment.

PMID: 16573862

Morphometric evaluation of the hydrocephalic brain: relationships with cognitive development.

Fletcher JM, Bohan TP, Brandt ME, Kramer LA, Brookshire BL, Thorstad K, Davidson KC, Francis DJ, McCauley SR, Baumgartner JE. Morphometric evaluation of the hydrocephalic brain: relationships with cognitive development. Childs Nervous System. 1996 Apr;12(4):192-9.

The effects of early hydrocephalus and related brain anomalies on cognitive skills are not well understood. In this study, magnetic resonance scans were obtained from 99 children aged from 6 to 13 years with either shunted hydrocephalus (n = 42) or arrested (unshunted) hydrocephalus (n = 19), from patient controls with no hydrocephalus (n = 23), and from normal, nonpatient controls (n = 15). Lateral ventricle volumes and area measurements of the internal capsules and centra semiovale in both hemispheres were obtained from these scans, along with area measurements of the corpus callosum. Results revealed reductions in the size of the corpus callosum in the shunted hydrocephalus group. In addition, lateral ventricle volumes were larger and internal capsule areas were smaller in both hemispheres in children with shunted and arrested hydrocephalus. The centra semiovale measurements did not differentiate the groups. Correlating these measurements with concurrent assessments of verbal and nonverbal cognitive skills, motor abilities, and executive functions revealed robust relationships only between the area of the corpus callosum and nonverbal cognitive skills and motor abilities. These results support the theory of a prominent role for the corpus callosum defects characteristic of many children with shunted hydrocephalus in the spatial cognition deficits commonly observed in these children.

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.