Comparison of prenatal and postnatal treatments of spina bifida in Poland - a randomized, single-center study

Zamłyński J, Olejek A, Bohosiewicz J, Koszutski T, Ziomek G, Horzelska E, Gajewska-Kucharek A, Maruniak-Chudek I, Herman-Sucharska I, Kluczewska E, Horak S, Bodzek P, Zamłyński M, Kowalik J, Horzelski T. (2013).  Comparison of prenatal and postnatal treatments of spina bifida in Poland - a randomized, single-center study.

Journal of Maternal-Fetal and Neonatal Medicine. 2013 Oct 25. [Epub ahead of print]

Abstract

Abstract Objective: The aim of the study was a randomized comparison of the outcomes of intrauterine myelomeningocele repairs (IUMR) in type II Chiari malformation (II CM) fetuses with clinical data of newborns and infants operated on postnatally. Methods: The study group (SG) comprised of 46 pregnant women whose type II CM children underwent IUMR, while 47 pregnant women whose type II CM children were operated on postnatally constituted the control group (CG). A total of 24 SG and 20 CG patients reached the endpoint of the study. Results: High incidence of PROM (24 (52.2%), CI 3.74 (1.69-8.26) (p<0 .001="" 0.35="" 1.86="" 16="" able="" adaptive="" adverse="" after="" and="" are="" as="" can="" cg="" chiari="" children="" ci="" closure="" compared="" conclusions:="" contrast="" controls.="" controls="" course="" equipment.="" especially="" evolution="" for="" from="" further="" group="" ii="" implantation="" in="" independently.="" ipprom="" iumr.="" iumr="" labor="" lower="" lowers="" malformation.="" measures="" mmc="" need="" needed="" none="" noted="" of="" on="" p="" postnatally="" postoperative="" prenatal="" preterm="" preventive="" respectively="" shunt="" significantly="" statistically="" studies="" study="" surgeries="" the="" to="" treated="" two="" type="" vp="" walk="" was="" without="">

 

PMID:24156622

Auditory interhemispheric transfer in relation to patterns of partial agenesis and hypoplasia of the corpus callosum in spina bifida meningomyelocele.

Hannay HJ, Walker A, Dennis M, Kramer L, Blaser S, Fletcher JM. (2008) Auditory interhemispheric transfer in relation to patterns of partial agenesis and hypoplasia of the corpus callosum in spina bifida meningomyelocele.
J Int Neuropsychol Soc. 2008 Sep;14(5):771-81.


Spina bifida meningomyelocele with hydrocephalus (SBM) is commonly associated with anomalies of the corpus callosum (CC). We describe MRI patterns of regional CC agenesis and relate CC anomalies to functional laterality based on a dichotic listening test in 90 children with SBM and 27 typically developing controls. Many children with SBM (n = 40) showed regional CC anomalies in the form of agenesis of the rostrum and/or splenium, and a smaller number (n = 20) showed hypoplasia (thinning) of all CC regions (rostrum, genu, body, and splenium). The expected right ear advantage (REA) was exhibited by normal controls and children with SBM having a normal or hypoplastic splenium. It was not shown by children with SBM who were left handed, missing a splenium, or had a higher level spinal cord lesion. Perhaps the right hemisphere of these children is more involved in processing some aspects of linguistic stimuli.

PMID: 18764972

Posterior fossa decompression and the cerebellum in Chiari type II malformation: a preliminary MRI study

Salman MS. (2011) Posterior fossa decompression and the cerebellum in Chiari type II malformation: a preliminary MRI study. Childs Nerv Syst. 2011 Mar;27(3):457-62.

OBJECTIVES:
Chiari type II malformation (CII) is a congenital deformity of the hindbrain. The posterior fossa and cerebellum are small in CII. The cerebellar atrophy is associated with cognitive and motor deficits. Brainstem compression occurs in some patients with CII for whom posterior fossa decompression may be life saving. The aim was to determine whether posterior fossa decompression can prevent or reduce the cerebellar atrophy in CII.

METHODS:
Cerebellar volumes and their tissue types (gray matter, white matter, and CSF volumes) from brain MRI were compared among four CII patients, aged 9.5 to 16.5 years, who had had posterior fossa decompression in infancy, 28 CII patients who had not had posterior fossa decompression, and ten age-matched normal controls. Parametric and non-parametric tests investigated group differences.

RESULTS:
Compared to controls, mean cerebellar volume was significantly smaller in CII patients (p<0.0001). Mean CSF volume within the cerebellar fissures and fourth ventricle was significantly smaller in patients without posterior fossa decompression compared to the CII patients who had the decompression, p=0.043. Mean CSF volume of the latter group was similar to the controls. Other cerebellar volumetric measurements did not differ between the CII groups. CONCLUSIONS: Posterior fossa decompression normalizes CSF spaces within the posterior fossa in CII but does not prevent the cerebellar atrophy. The author proposes that surgical expansion of the posterior fossa should be considered in infants with CII who have a significantly small posterior fossa, to prevent or reduce the deficits associated with the cerebellar atrophy.

PMID: 21221976

Cerebellar vermis morphology in children with spina bifida and Chiari type II malformation.

Salman MS, Blaser SE, Sharpe JA, Dennis M. (2006) Cerebellar vermis morphology in children with spina bifida and Chiari type II malformation.
Childs Nerv Syst. 2006 Apr;22(4):385-93. Epub 2005 Dec 22.

OBJECTIVE:
Posterior fossa size and cerebellar weight and volume are reduced in Chiari type II malformation (CII). This is assumed to affect the cerebellum uniformly. We quantified the presumed reduction in vermis size on magnetic resonance imaging (MRI).

METHODS:
A midsagittal brain MRI slice was selected from each of 68 participants with CII (mean age 13 years). Control participants were 28 typically developing children (mean age 14.1 years). Midsagittal surface areas occupied by the intracranial fossa, posterior fossa, vermis, and its lobules were measured.

CONCLUSIONS:
Mean posterior fossa area was significantly smaller (P<0.003), although mean vermis area was significantly larger (P<0.0001), in participants with CII than in control participants. This expansion involved vermis lobules I-V and VI-VII areas (P<0.0001). The midsagittal vermis was expanded and not reduced in size in participants with CII. This is attributed to compressive displacement of midline structures within the confines of a small posterior fossa.

PMID: 16374591

Cerebellar motor function in spina bifida meningomyelocele.

Dennis M, Salman MS, Juranek J, Fletcher JM (2010) Cerebellar motor function in spina bifida meningomyelocele. Cerebellum. 2010 Dec;9(4):484-98.

Spina bifida meningomyelocele (SBM), a congenital neurodevelopmental disorder, involves dysmorphology of the cerebellum, and its most obvious manifestations are motor deficits. This paper reviews cerebellar neuropathology and motor function across several motor systems well studied in SBM in relation to current models of cerebellar motor and timing function. Children and adults with SBM have widespread motor deficits in trunk, upper limbs, eyes, and speech articulators that are broadly congruent with those observed in adults with cerebellar lesions. The structure and function of the cerebellum are correlated with a range of motor functions. While motor learning is generally preserved in SBM, those motor functions requiring predictive signals and precise calibration of the temporal features of movement are impaired, resulting in deficits in smooth movement coordination as well as in the classical cerebellar triad of dysmetria, ataxia, and dysarthria. That motor function in individuals with SBM is disordered in a manner phenotypically similar to that in adult cerebellar lesions, and appears to involve similar deficits in predictive cerebellar motor control, suggests that age-based cerebellar motor plasticity is limited in individuals with this neurodevelopmental disorder.

PMID: 20652468

 

The cerebellum in children with spina bifida and Chiari II malformation: Quantitative volumetrics by region.

Juranek J, Dennis M, Cirino PT, El-Messidi L, Fletcher JM. (2010) The cerebellum in children with spina bifida and Chiari II malformation: Quantitative volumetrics by region. Cerebellum. 2010 Jun;9(2):240-8.

Few volumetric MRI studies of the entire cerebellum have been published; even less quantitative information is available in patients with hindbrain malformations, including the Chiari II malformation which is ubiquitous in patients with spina bifida meningomyelocele (SBM). In the present study, regional volumetric analyses of the cerebellum were conducted in children with SBM/Chiari II and typically developing (TD) children. Total cerebellar volume was significantly reduced in the SBM group relative to the TD group. After correcting for total cerebellum volume, and relative to the TD group, the posterior lobe was significantly reduced in SBM, the corpus medullare was not different, and the anterior lobe was significantly enlarged. Children with thoracic level lesions had smaller cerebellar volumes relative to those with lumbar/sacral lesions, who had smaller volumes compared to TD children. The reduction in cerebellar volume in the group with SBM represents not a change in linear scaling but rather a reconfiguration involving anterior lobe enlargement and posterior lobe reduction.

PMID: 20143197

Anomalous development of brain structure and function in spina bifida myelomeningocele.

Juranek J, Salman MS. (2012) Anomalous development of brain structure and function in spina bifida myelomeningocele.
Dev Disabil Res Rev. 2010;16(1):23-30.

Spina bifida myelomeningocele (SBM) is a specific type of neural tube defect whereby the open neural tube at the level of the spinal cord alters brain development during early stages of gestation. Some structural anomalies are virtually unique to individuals with SBM, including a complex pattern of cerebellar dysplasia known as the Chiari II malformation. Other structural anomalies are not necessarily unique to SBM, including altered development of the corpus callosum and posterior fossa. Within SBM, tremendous heterogeneity is reflected in the degree to which brain structures are atypical in qualitative appearance and quantitative measures of morphometry. Hallmark structural features of SBM include overall reductions in posterior fossa and cerebellum size and volume. Studies of the corpus callosum have shown complex patterns of agenesis or hypoplasia along its rostral-caudal axis, with rostrum and splenium regions particularly susceptible to agenesis. Studies of cortical regions have demonstrated complex patterns of thickening, thinning, and gyrification. Diffusion tensor imaging studies have reported compromised integrity of some specific white matter pathways. Given equally complex ocular motor, motor, and cognitive phenotypes consisting of relative strengths and weaknesses that seem to align with altered structural development, studies of SBM provide new insights to our current understanding of brain structure-function associations.

PMID: 20419768

Sustained attention in children with two etiologies of early hydrocephalus.

Swartwout, Maegan D.; Cirino, Paul T.; Hampson, Amy W.; Fletcher, Jack M.; Brandt, Michael E.; Dennis, Maureen; Sustained attention in children with two etiologies of early hydrocephalus. Neuropsychology, Vol 22(6), Nov, 2008. pp. 765-775.

Department of Psychology, University of Houston, Houston, TX 77204-5355, USA. mdswartwout@uh.edu

Several studies have shown that children with spina bifida meningomyelocele (SBM) and hydrocephalus have attention problems on parent ratings and difficulties in stimulus orienting associated with a posterior brain attention system. Less is known about response control and inhibition associated with an anterior brain attention system. Using the Gordon Vigilance Task (Gordon, 1983), we studied error rate, reaction time, and performance over time for sustained attention, a key anterior attention function, in 101 children with SBM, 17 with aqueductal stenosis (AS; another condition involving congenital hydrocephalus), and 40 typically developing controls (NC). In SBM, we investigated the relation between cognitive attention and parent ratings of inattention and hyperactivity and explored the impact of medical variables. Children with SBM did not differ from AS or NC groups on measures of sustained attention, but they committed more errors and responded more slowly. Approximately one-third of the SBM group had attention symptoms, although parent attention ratings were not associated with task performance. Hydrocephalus does not account for the attention profile of children with SBM, which also reflects the distinctive brain dysmorphologies associated with this condition.

PMID: 18999350

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

The Chiari malformations: A constellation of anomalies

Robert M. Shuman RM. (1995) The Chiari malformations: A constellation of anomalies. Seminars in Pediatric Neurology. 1995 Sep;2(3):220-6. Review.


The Chiari malformations form a group of abnormalities that are pathogenetically interrelated. The most important member of the group is the Chiari type II malformation, known as the Arnold-Chiari malformation. Its cardinal features are the myelomeningocele in the thoraco-lumbar spine, the venting of the intracranial cerebrospinal fluid through the central canal, the hypoplasia of the posterior fossa, the herniation of hindbrain into the cervical spinal canal, and the compressive damage to cranial nerves. Some of the abnormalities are progressive, and thus treatable. Limitation of progression may improve outcomes. The challenges to our treatment programs involve early diagnosis, delivery by Caesarean section, emergent closure of the neural plaque and prophylaxis of hydrocephalus, anticipatory prevention of the neurological compression syndromes, multidisciplinary teams, and age-appropriate interventions.

Partial agenesis of the corpus callosum in spina bifida meningomyelocele and potential compensatory mechanisms.

Hannay HJ, Dennis M, Kramer L, Blaser S, Fletcher JM. (2009) Partial agenesis of the corpus callosum in spina bifida meningomyelocele and potential compensatory mechanisms.
Journal of Clinical and Experimental Neuropsychology. 2009 Feb;31(2):180-94.

After a review of Arthur Benton's conceptual and methodological contributions to the understanding of normal and pathological development, we discuss agenesis of the corpus callosum (CC), criteria for potential neuroanatomical compensatory mechanisms in CC agenesis, and the results of an examination of magnetic resonance imaging (MRI) data of the CC in 193 children with spina bifida meningomyelocele (SBM). There were 26 CC regional patterns. Although complete agenesis did not occur, partial agenesis was observed in 102 children and within 15 CC regional patterns. Only 4.1% had a normal CC. Quantitative assessment of the area of the CC in 26 NC children and 68 children with SBM revealed that all subgroups with CC anomalies had smaller areas than did a subgroup with a normal CC. Areas were especially small in rostral/splenial agenesis and splenial agenesis but larger with rostral agenesis. Subgroups with normal/hypoplastic regions or complete hypoplasia also had CC areas that were smaller than normal but larger than the areas for the splenial agenesis groups. The relative rarity of anterior commissure enlargement (3.1%) and longitudinal bundles of Probst (0.1%) suggest that these particular fiber tract anomalies are unlikely candidates for structural compensatory mechanisms. The hippocampal commissure, enlarged in 13%, may be a more promising candidate. Overall, however, the functionality of anomalous fiber tracts and commissures in SBM is yet to be determined.

PMID: 19052950

White matter microstructural abnormalities in children with spina bifida myelomeningocele and hydrocephalus: a diffusion tensor tractography study of

Hasan KM, Eluvathingal TJ, Kramer LA, Ewing-Cobbs L, Dennis M, Fletcher JM.
White matter microstructural abnormalities in children with spina bifida myelomeningocele and hydrocephalus: a diffusion tensor tractography study of the association pathways.
Journal of Magnetic Resonance Imaging: JMRI. 2008 Apr;27(4):700-9.

PURPOSE: To quantify microstructural abnormalities in the major association pathways of children affected by spina bifida myelomeningocele (SBM) and shunted hydrocephalus using whole-brain diffusion tensor imaging (DTI).

MATERIALS AND METHODS: The institutional review board approved this Health Insurance Portability and Accountability Act (HIPAA)-compliant study and written informed consent/assent were obtained prior to the study. The 69 participants included 38 children with SBM and shunted hydrocephalus (age mean +/- SD = 12.30 +/- 2.10 years; 22 boys; 10 left-handed) and 31 age- and sex-matched normally-developing children (11.56 +/- 2.72 years; 15 boys, four left-handed). Diffusion tensor tractography (DTT) was performed to delineate and quantify bilaterally four major association pathways (arcuate, inferior longitudinal, inferior fronto-occipital, and uncinate fasciculi).

RESULTS: The group with SBM did not exhibit the pattern of age-related decreases in the diffusivities observed in the controls. The transverse and axial diffusivities were significantly elevated in most of the white matter pathways of the participants with SBM. The fractional anisotropy (FA) was significantly lower in most of the association pathways. Many of the association pathways were not traceable in some participants with SBM compared to the controls at the selected FA thresholds.

CONCLUSION: DTT revealed diffusion tensor characteristics of abnormal development (nonvisualization/poor visualization of tracts, downward arrow FA, upward arrow diffusivities), impairment in myelination (upward arrow transverse diffusivity) as well as abnormalities in intrinsic axonal characteristics and extraaxonal/extracellular space (upward arrow axial diffusivity) in the association pathways of the SBM children. The differences in the diffusion metrics observed in the children with SBM are suggestive of abnormal white matter development and persistent degeneration with increased age. (c) 2008 Wiley-Liss, Inc.

PMID: 18302204

Covert orienting to exogenous and endogenous cues in children with spina bifida

Dennis M, Edelstein K, Copeland K, Frederick J, Francis DJ, Hetherington R, Blaser SE, Kramer LA, Drake JM, Brandt ME, Fletcher JM. Covert orienting to exogenous and endogenous cues in children with spina bifida. Neuropsychologia. 2005;43(6):976-87. Epub 2004 Dec 8.

Children with spina bifida meningomyelocele and hydrocephalus (SBM) have congenital dysmorphology of the midbrain and thinning of the posterior cortex, brain regions associated with the control of covert orienting. We studied cued covert orienting in 92 children with SBM, and 40 age-matched typically developing controls. Cues were of three types: exogenous (luminance change in a peripheral box either valid or invalid for upcoming target location), endogenous arrow (a central arrow either valid or invalid for upcoming target location), or endogenous word (a central word either valid or invalid for upcoming target location). Compared to controls, children with SBM showed slowed covert orienting to both exogenous and endogenous cues and a higher cost of attentional disengagement (e.g., a greater cue-validity effect) for exogenous although not for endogenous cues. Covert orienting deficits were associated with midbrain dysmorphology in the form of beaking of the tectum, and with right posterior brain volume loss.

PMID: 15716168

Space-based inhibition of return in children with spina bifida

Dennis M, Edelstein K, Copeland K, Frederick JA, Francis DJ, Hetherington R, Blaser SE, Kramer LA, Drake JM, Brandt ME, Fletcher JM. Space-based inhibition of return in children with spina bifida. Neuropsychology. 2005 Jul;19(4):456-65.

Inhibition of return (IOR) refers to an increase in time to react to a target in a previously attended location. Children with spina bifida meningomyelocele (SBM) and hydrocephalus have congenital dysmorphology of the midbrain, a brain region associated with the control of covert orienting in general and with IOR in particular. The authors studied exogenously cued covert orienting in 8- to 19-year-old children and adolescents (84 with SBM and 37 age-matched, typically developing controls). The exogenous cue was a luminance change in a peripheral box that was 50% valid for the upcoming target location. Compared with controls, children with SBM showed attenuated IOR in the vertical plane, a deficit that was associated with midbrain dysmorphology in the form of tectal beaking but not with posterior brain volume loss. The data add to the emerging evidence for SBM deficits in attentional orienting to salient information. (c) 2005 APA, all rights reserved.

PMID: 16060820

Chiari-II malformation: a biometric analysis

Tsai T, Bookstein FL, Levey E, Kinsman SL. Chiari-II malformation: a biometric analysis. European Journal of Pediatric Surgery. 2002 Dec;12 Suppl 1:S12-8.

INTRODUCTION: Chiari-II malformation is a complex set of anatomic abnormalities of the posterior fossa, brainstem, and cerebellum seen in myelomeningocele. Previous studies have tried to understand this condition and its clinical consequences by studying a few fixed anatomic landmarks as dependent variables and clinical symptoms as outcome variables. These studies have led to conflicting and limited results. As a first step towards a more comprehensive study of the structural-functional relationships in Chiari-II malformation, we undertook a biometric case-series analysis of a group of individuals with MMC, using both traditional methods to study size, and thin-plate spline methodology to study shape.

MATERIALS AND METHODS: The traditional analysis was a retrospective, randomly obtained case-series of 25 individuals with myelomeningocele and Chiari-II malformation. MRIs were digitized for biometric analysis of the component structures and compared to 25 controls. Landmarks on the digitized images were measured using Scion Image. Data were statistically analyzed using SPSS. The thin-plate spline analysis used a subset of these individuals (n = 14). Landmarks on digitized MRIs were identified and marked with TPSDig software. Landmark data was then imported into Splus to generate a series of shape variables. Statistical analysis using Splus was then undertaken. RESULTS: Traditional analysis revealed relationships between vermian herniation and pontomedullary junction position (p < 0.05) as well as between the height (and overall size) of the posterior fossa and degree of vermian herniation (p < 0.05). The degree of brainstem herniation/elongation did not correlate with the degree of vermian herniation. The shape analysis revealed that there is as much shape variability within the group of Chiari-II patients as there is between this group and unaffected controls. Thin-plate spline analysis shows that the position of the caudal-most aspect of the vermis is the point of greatest brain rearrangement; likewise, the opisthion is the point of greatest bony rearrangement. Partial least-squares analysis shows that in Chiari-II patients, a strong correlation (r = 0.821) exists between the extent to which the brain is warped (specifically, in regard to vermian descent) and the extent to which the bone is warped (specifically, in regard to the displacement of the opisthion) (p < 0.05).

CONCLUSION: Traditional biometric analysis of size confirms that the degree of vermian herniation and cervicomedullary junction herniation are independent variables in Chiari-II malformation. Posterior fossa size is an important factor in explaining the variability of vermian herniation. The relationship between IPN position and vermian herniation suggests the possibility of a common etiology. The phenomenon of cervicomedullary junction descent appears to be independent, suggesting a different etiology. Analysis of shape indicated that shape changes in bone and brain are related, and that the Chiari-II-associated abnormalities vary greatly in their degree of abnormality. The extreme morphological variability argues against the use of mean differences as a statistical technique in analyzing morphological abnormalities in the structures we investigated.

PMID: 12541208

Limbic tract anomalies in pediatric myelomeningocele and Chiari II malformation

Vachha B, Adams RC, Rollins NK. Limbic tract anomalies in pediatric myelomeningocele and Chiari II malformation: anatomic correlations with memory and learning--initial investigation. Radiology. 2006 Jul;240(1):194-202.

PURPOSE: To prospectively determine anomalies of limbic tracts and to describe the relationship between these anomalies, seen on diffusion-tensor magnetic resonance (MR) and fiber tract (FT) reconstruction images, and learning and memory in children with myelomeningocele (MM) and Chiari II malformation.

MATERIALS AND METHODS: The investigation was HIPAA compliant and approved by institutional review boards; informed consent was obtained. In seven male and six female patients (aged 6 months to 16 years) with MM and Chiari II malformation, diffusion-tensor imaging and FT reconstruction were performed. FT reconstruction was generated with fractional anisotropy continuous tracking algorithm and manually drawn regions of interest. Limbic tract abnormalities were assessed on FT reconstruction images by an experienced pediatric neuroradiologist blinded to results of cognitive testing. Nine patients met criteria for memory and learning testing by a trained cognitive neuroscientist blinded to MR results. Exact Wilcoxon rank sum test was used to compare performance with learning and memory tasks in two groups.

RESULTS: Eleven of 13 patients had defects within fornices and/or cingulum; three patients had aberrant fibers of cingulum. In nine patients, six had deficits in general memory; four, in learning; and four, in both. Atresia or hypoplasia of crura and body of fornices was noted in six patients with memory deficits and four patients with learning deficits. Five of six patients with memory deficits and three of four with learning deficits had hypoplasia or atresia of cingulum. Exact Wilcoxon rank sum test demonstrated significantly poorer performance for nonverbal immediate recall tasks in patients with anomalies of the fornix compared with those without (P = .04, exact two-tailed test).

CONCLUSION: Diffusion-tensor and FT reconstruction images revealed that limbic fiber abnormalities were common in patients with MM and Chiari II malformation. Nonverbal immediate recall task performance appeared to be related to abnormalities of the fornix.

PMID: 16793979

Language development in children with spina bifida

Fletcher JM, Barnes M, Dennis M. Language development in children with spina bifida. Seminars in Pediatric Neurology. 2002 Sep;9(3):201-8. Review.

Spina bifida meningomyelocele (SBM) is the most common severely disabling birth defect in North America. It is a disorder of the central nervous system that includes, in addition to the defining spinal dysraphism, congenital malformations of the cerebellum and corpus callosum that, along with hydrocephalus, produces a range of cognitive and motor difficulties, including language. In the language domain, many children with SBM demonstrate adequate development of language at the level of form and content (grammar and lexicon). However, most children with SBM experience significant difficulties in the construction of meaning and in pragmatic communication, both of which require flexible language processing in real time. Assessment and intervention should specifically attend to the development of meaning construction and semantic-pragmatic communication.

PMID: 12350041

Peripersonal spatial attention in children with spina bifida

Dennis M, Edelstein K, Frederick J, Copeland K, Francis D, Blaser SE, Kramer LA, Drake JM, Brandt M, Hetherington R, Fletcher JM. Peripersonal spatial attention in children with spina bifida: associations between horizontal and vertical line bisection and congenital malformations of the corpus callosum, midbrain, and posterior cortex. Neuropsychologia. 2005;43(14):2000-10.

Horizontal and vertical line bisection was studied in 129 children and adolescents between 8 and 19 years of age, one group (n=32) of typically developing controls and one group (n=97) with spina bifida (SBM), a neurodevelopmental disorder associated with dysmorphology of the corpus callosum, posterior cortex, and midbrain. For each participant, structural brain MRIs were analyzed qualitatively to identify beaking of the midbrain tectum and corpus callosum agenesis and hypoplasia and quantitatively by segmentation and volumetric analyses of regional cortical white and gray matter. Each group showed the line length effect, whereby greater estimation errors are made with longer lines. The group with SBM differed from controls in terms of both accuracy and variability of line bisection. Children with SBM showed pseudoneglect, attending more than controls to left hemispace. The extent of rightward bisection bias was unrelated to right posterior brain volumes, although an intact corpus callosum during development moderated and normalized the exaggerated leftward line bisection bias. More children with SBM than controls attended to inferior hemispace. A normal midbrain and greater posterior cortex volume during development moderated and normalized the downward bias. Children with SBM showed more intra-subject variability than controls. Line bisection in children with SBM reflects three deficits: an exaggerated attentional bias to left hemispace, an abnormal attentional bias to inferior hemispace; and a larger zone of subjective uncertainty in bisection judgments.

PMID: 15893777

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

Motor learning in children with spina bifida: intact learning and performance on a ballistic task

Dennis M, Jewell D, Edelstein K, Brandt ME, Hetherington R, Blaser SE, Fletcher JM. Motor learning in children with spina bifida: intact learning and performance on a ballistic task. Journal of the International Neuropsychological Society. 2006 Sep;12(5):598-608.

Learning and performance on a ballistic task were investigated in children with spina bifida meningomyelocele (SBM), with either upper level spinal lesions (n = 21) or lower level spinal lesions (n = 81), and in typically developing controls (n = 35). Participants completed three phases (20 trials each) of an elbow goniometer task that required a ballistic arm movement to move a cursor to one of two target positions on a screen, including (1) an initial learning phase, (2) an adaptation phase with a gain change such that recalibration of the ballistic arm movement was required, and (3) a learning reactivation phase under the original gain condition. Initial error rate, asymptotic error rate, and learning rate did not differ significantly between the SBM and control groups. Relative to controls, the SBM group had reduced volumes in the cerebellar hemispheres and pericallosal gray matter (the region including the basal ganglia), although only the pericallosal gray matter was significantly correlated with motor adaptation. Congenital cerebellar dysmorphology is associated with preserved motor skill learning on voluntary, nonreflexive tasks in children with SBM, in whom the relative roles of the cerebellum and basal ganglia may differ from those in the adult brain.

PMID: 16961941