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

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

Neurobiology of perceptual and motor timing in children with spina bifida in relation to cerebellar volume

Dennis M, Edelstein K, Hetherington R, Copeland K, Frederick J, Blaser SE, Kramer LA, Drake JM, Brandt M, Fletcher JM. Neurobiology of perceptual and motor timing in children with spina bifida in relation to cerebellar volume. Brain. 2004 Jun;127(Pt 6):1292-301. Epub 2004 Apr 6.

The cerebellum is important for perceptual and motor timing in the mature brain, but the timing function of the cerebellum in the immature brain is less well understood. We investigated timing in children with spina bifida meningomyelocele (SB), a neural tube defect that involves cerebellar dysgenesis, and in age-matched controls. Specifically, we studied perceptual timing (judgements of 400 ms duration) and motor timing (isochronous motor tapping); measured cerebellar volumes; and related perceptual and motor timing to each other and to cerebellar volume measurements. Children with SB had impairments in the perception of duration (around 400 ms) but not frequency (around 3000 Hz), showing that their perceptual timing deficit was not a generalized auditory impairment. Children with SB had motor timing deficits on unpaced but not paced isochronous tapping, and their unpaced timing performance was associated with clock variance rather than with motor implementation. Perceptual and motor timing were correlated, suggesting that children with SB have impairments in a central timing mechanism. Children with SB, especially those with upper spinal cord lesions, had significant cerebellar volume reductions in grey and white matter, as well as different regional patterns of grey matter, white matter and CSF. Duration perception was correlated with cerebellar volumes, and the number of valid tapping trials was correlated with cerebellar volumes in the SB group, which data demonstrate structure-function relations between timing and cerebellar volumes.

PMID: 15069019
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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

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

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

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

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.