Aggressive surgical management of patients with Chiari II malformation and brainstem dysfunction.

Rahman M, Perkins LA, Pincus DW. Aggressive surgical management of patients with Chiari II malformation and brainstem dysfunction. Pediatric Neurosurgery. 2009;45(5):337-44. 11.

BACKGROUND/AIMS:
Chiari II malformation represents a group of developmental abnormalities involving the caudal displacement of the cervicomedullary junction, pons, fourth ventricle, and medulla. This constellation of malformations is strongly associated with myelomeningocele (MM) and is a known cause of neurologic deterioration in older MM patients. We describe the evaluation and management of 4 adult MM patients who presented with brainstem compression and a retroflexed odontoid who were subject to aggressive surgical management including occipitocervical (OC) fusion with good clinical results.

METHODS:
Four MM patients who underwent OC fusion for new-onset brainstem dysfunction and myelopathy were identified in the practice of the principal investigator (D.W.P.) from 2003 to 2008.

RESULTS:
The initial evaluation of these patients included consideration of other diagnoses, such as hydrocephalus due to shunt malfunction and tethered cord. These patients were treated with aggressive surgical management. In some cases, multiple surgeries were performed. All 4 patients were treated with cervical decompression and OC fixation and initially had good outcomes. No patients required transoral decompression. Three of the 4 had stable improvement at their last follow-up appointment (mean follow-up of 9 months).

CONCLUSION:
Late deterioration in older MM patients may be secondary to brainstem or cervical spinal cord compression from ventral odontoid compression and Chiari II malformation, hydrocephalus, hydromyelia, or tethered cord. These patients may benefit from more than one surgery. Posterior decompression and OC fusion can avoid a morbid transoral odontoid resection, greatly improve patients' symptoms and prevent further neurologic decline.

PMID: 19907196

Symptom recurrence after suboccipital decompression for pediatric Chiari I malformation: analysis of 256 consecutive cases.

McGirt MJ, Attenello FJ, Atiba A, Garces-Ambrossi G, Datoo G, Weingart JD, Carson B, Jallo GI. Symptom recurrence after suboccipital decompression for pediatric Chiari I malformation: analysis of 256 consecutive cases. Childs Nerv Syst. 2008 Nov;24(11):1333-9.

OBJECTIVE:
Symptom recurrence remains a problem for some patients after surgical decompression for Chiari I malformation. We set out to identify variables at presentation that could identify subgroups most likely to experience incomplete symptom relief after hindbrain decompression for Chiari I malformation.

MATERIALS AND METHODS:
We retrospectively reviewed the records of all pediatric patients undergoing first-time suboccipital decompression for Chiari I malformation over a 10-year period. Measured outcomes included (1) persistence or recurrence of symptoms regardless of severity and (2) need for revision decompression.

RESULTS:
Two hundred fifty-six children (10 5 years old) underwent surgery for Chiari I malformation and were followed up for a mean of 27 months. Presenting symptoms included headache in 192 (75%) patients and brainstem or cranial nerve symptoms in 68 (27%) patients. Fifty-seven (22%) patients experienced mild to moderate symptom recurrence. Nineteen (7%) patients required revision decompression for significant symptom recurrence. Headache was 70% more likely to persist or recur versus cranial nerve or brainstem symptoms (relative risk 1.70, p < 0.05). Vertigo and frontal headache independently increased the odds of symptom recurrence 2.9- and 1.5-fold, respectively. Each increasing year of preoperative headache duration was independently associated with 15% increase in likelihood of symptom persistence (p < 0.05). Severe tonsilar ectopia (caudal to C2 lamina) was twice as likely to require revision decompression (14% versus 6%). CONCLUSION: In our experience, recurrence of mild symptomatology not severe enough to justify revision surgery may occur in nearly a fifth of patients after surgery. Headache was more likely to recur than objective cranial nerve or brainstem symptoms. Increasing duration of headaches, frontal headaches, and vertigo may be more refractory symptoms of Chiari I malformation. PMID: 18516609

Brainstem dysfunction in chiari malformation presenting as profound hypoglycemia: presentation of four cases, review of the literature, and conjecture as to mechanism.

Rekate HL, Nadkarni TD, Teaford PA, Wallace D.
Brainstem dysfunction in chiari malformation presenting as profound hypoglycemia: presentation of four cases, review of the literature, and conjecture as to mechanism. Neurosurgery. 1999 Aug;45(2):386-91. Review.

OBJECTIVE:
We report four patients whose cases resulted in our observation that profound hypoglycemia resulting from intermittent hyperinsulinism plays a significant role in patients with brainstem dysfunction from Chiari I or II malformations who have intermittent autonomic dysfunction ("blue spells").

METHODS:
The records of four children with severe brainstem dysfunction associated with hindbrain herniation (Chiari I or II malformation) were reviewed retrospectively. Each patient had severe lower cranial nerve dysfunction that required tracheotomy and feeding tube placement. After we found that profound hypoglycemia had occurred during a spell of autonomic dysfunction in one patient, the charts of the other three patients were reviewed for evidence of hypoglycemia. Now, whenever one of them has evidence of autonomic dysfunction, prospective studies of glucose and insulin levels are performed. Three of the patients had Chiari II malformation in association with myelomeningocele, and one patient had a Chiari I malformation resulting from Pfeiffer's syndrome.

RESULTS:
Hypoglycemia occurred in these patients episodically, and usually when their shunts were functioning. The hypoglycemia was associated with hyperinsulinemia in each patient. The brainstem structures of these children (presumably the dorsal motor nuclei of the vagus) were extremely sensitive to changes in local or regional intracranial pressure. These changes were triggered by intermittent shunt failure, agitation from pain, abdominal distention from constipation, and retention of CO2. In patients with Chiari malformations, even mild increases in intracranial pressure lead to brainstem dysfunction. One possible explanation is that pressure on the deformed Xth cranial nerve nuclei may lead to insulin release and life-threatening hypoglycemia. Continuous-drip feeds are necessary to prevent this complication.

CONCLUSION:
Patients with severe intermittent brainstem dysfunction after decompression of Chiari I or Chiari II malformations should have laboratory studies of glucose levels performed at the time of the episodes to rule out hypoglycemia.


PMID: 10449086

Spina bifida subtypes and sub-phenotypes by maternal race/ethnicity in the National Birth Defects Prevention Study.

Agopian AJ, Canfield MA, Olney RS, Lupo PJ, Ramadhani T, Mitchell LE, Shaw GM, Moore CA; (2011) Spina bifida subtypes and sub-phenotypes by maternal race/ethnicity in the National Birth Defects Prevention Study. Am J Med Genet A. 2011 Dec 2.

Spina bifida refers to a collection of neural tube defects, including myelomeningocele, meningocele, and myelocele (SB(M) ), as well as lipomyelomeningocele and lipomeningocele (SB(L) ). Maternal race/ethnicity has been associated with an increased risk for spina bifida among offspring. To better understand this relationship, we evaluated different spina bifida subtypes (SB(M) vs. SB(L) ) and sub-phenotypes (anatomic level or presence of additional malformations) by maternal race/ethnicity using data from the National Birth Defects Prevention Study. This study is a large, multisite, population-based study of nonsyndromic birth defects. Prevalence estimates were obtained using data from spina bifida cases (live births, fetal deaths, and elective terminations) and total live births in the study regions. From October 1997 through December 2005, 1,046 infants/fetuses with spina bifida were delivered, yielding a prevalence of 3.06 per 10,000 live births. Differences in the prevalences of SB(M) vs. SB(L) , isolated versus non-isolated SB(M) , and lesion level in isolated SB(M) among case offspring were observed by maternal race/ethnicity. Compared to non-Hispanic (NH) White mothers, offspring of Hispanic mothers had higher prevalences of each subtype and most sub-phenotypes, while offspring of NH Black mothers generally had lower prevalences. Furthermore, differences in race/ethnicity among those with isolated SB(M) were more pronounced by sex. For instance, among male offspring, the prevalence of isolated SB(M) was significantly higher for those with Hispanic mothers compared to NH White mothers [prevalence ratio (PR): 1.55, 95% confidence interval: 1.23-1.95]. These findings provide evidence that certain spina bifida subtypes and sub-phenotypes may be etiologically distinct.

PMID:
22140002

A genetic signature of spina bifida risk from pathway-informed comprehensive gene-variant analysis.

Marini NJ, Hoffmann TJ, Lammer EJ, Hardin J, Lazaruk K, Stein JB, Gilbert DA, Wright C, Lipzen A, Pennacchio LA, Carmichael SL, Witte JS, Shaw GM, Rine J. (2011) A genetic signature of spina bifida risk from pathway-informed comprehensive gene-variant analysis. PLoS One. 2011;6(11):e28408.

Despite compelling epidemiological evidence that folic acid supplements reduce the frequency of neural tube defects (NTDs) in newborns, common variant association studies with folate metabolism genes have failed to explain the majority of NTD risk. The contribution of rare alleles as well as genetic interactions within the folate pathway have not been extensively studied in the context of NTDs. Thus, we sequenced the exons in 31 folate-related genes in a 480-member NTD case-control population to identify the full spectrum of allelic variation and determine whether rare alleles or obvious genetic interactions within this pathway affect NTD risk. We constructed a pathway model, predetermined independent of the data, which grouped genes into coherent sets reflecting the distinct metabolic compartments in the folate/one-carbon pathway (purine synthesis, pyrimidine synthesis, and homocysteine recycling to methionine). By integrating multiple variants based on these groupings, we uncovered two provocative, complex genetic risk signatures. Interestingly, these signatures differed by race/ethnicity: a Hispanic risk profile pointed to alterations in purine biosynthesis, whereas that in non-Hispanic whites implicated homocysteine metabolism. In contrast, parallel analyses that focused on individual alleles, or individual genes, as the units by which to assign risk revealed no compelling associations. These results suggest that the ability to layer pathway relationships onto clinical variant data can be uniquely informative for identifying genetic risk as well as for generating mechanistic hypotheses. Furthermore, the identification of ethnic-specific risk signatures for spina bifida resonated with epidemiological data suggesting that the underlying pathogenesis may differ between Hispanic and non-Hispanic groups.

PMID: 22140583

Prospective memory in adults with spina bifida.

Dennis M, Nelson R, Jewell D, Fletcher JM. (2010) Prospective memory in adults with spina bifida. Childs Nerv Syst. 2010 Dec;26(12):1749-55.

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

Working memory and information processing speed in children with myelomeningocele and shunted hydrocephalus: analysis of the children's paced auditory serial addition test.

Boyer KM, Yeates KO, Enrile BG. (2006) Working memory and information processing speed in children with myelomeningocele and shunted hydrocephalus: analysis of the children's paced auditory serial addition test. J Int Neuropsychol Soc. 2006 May;12(3):305-13.

Working memory and information processing speed were examined in children with myelomeningocele and shunted hydrocephalus using the Children's Paced Auditory Serial Addition Test (CHIPASAT). The CHIPASAT was administered to 31 children with myelomeningocele and shunted hydrocephalus and 27 healthy siblings, all between 8 and 15 years of age. They also completed other standardized measures of working memory and processing speed. Children with myelomeningocele made fewer correct responses than siblings, although the magnitude of group differences declined as the rate of stimulus presentation increased. Children with myelomeningocele also made fewer consecutive correct responses and were more likely to provide correct but nonconsecutive responses, suggesting that they responded in a way that circumvents the working memory demands of the task. Standardized measures of processing speed and working memory accounted for significant variance in CHIPASAT performance after controlling for age, group membership, math skill, and general intellectual functioning. The results indicate that children with myelomeningocele and shunted hydrocephalus display deficits in working memory and information processing speed, and suggest that the CHIPASAT may provide a valid measure of these skills.

PMID: 16903123

Arithmetic skills and their cognitive correlates in children with acquired and congenital brain disorder.

Ayr LK, Yeates KO, Enrile BG.(2005) Arithmetic skills and their cognitive correlates in children with acquired and congenital brain disorder. J Int Neuropsychol Soc. 2005 May;11(3):249-62.

Arithmetic skills and their cognitive correlates were studied in 24 children with myelomeningocele and shunted hydrocephalus (MM), 27 children with severe traumatic brain injuries (TBI), and 26 children with orthopedic injuries (OI). Their average age was 11.56 years (SD = 2.36). They completed the WRAT-3 Arithmetic subtest and a subtraction task consisting of 20 problems of varying difficulty, as well as measures of working memory, declarative memory, processing speed, planning skills, and visuospatial abilities. The MM group performed more poorly on the WRAT-3 Arithmetic subtest and the subtraction task than the other two groups, which did not differ from each other on either measure. The groups did not differ in the number of math fact errors or visual-spatial errors on the subtraction task, but the MM group made more procedural errors than the OI group. The five cognitive abilities explained substantial variance in performance on both arithmetic tests; processing speed, working memory, declarative memory, and planning accounted for unique variance. Exploratory analyses showed that the cognitive correlates of arithmetic skills varied across groups and ages. Congenital and acquired brain disorders are associated with distinct patterns of arithmetic skills, which are related to specific cognitive abilities.

PMID: 15892901

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

Brain mechanisms for reading and language processing in spina bifida meningomyelocele: a combined magnetic source- and structural magnetic resonance imaging study.

Simos PG, Papanicolaou AC, Castillo EM, Juranek J, Cirino PT, Rezaie R, Fletcher JM. (2011) Brain mechanisms for reading and language processing in spina bifida meningomyelocele: a combined magnetic source- and structural magnetic resonance imaging study. Neuropsychology. 2011 Sep;25(5):590-601.


OBJECTIVE:
The development of the ability to process spoken and written language depends upon a network of left hemisphere temporal, parietal, and frontal regions. The present study explored features of brain organization in children with spina bifida meningomyelocele (SBM) and shunted hydrocephalus, who commonly present with precocious development of word reading skills and preservation of vocabulary and grammar skills.

METHOD:
Eight children with SBM were compared with 15 IQ and reading-level matched, typically developing controls on MRI-based morphometric and Magnetic Source Imaging-derived neurophysiological profiles.

RESULTS:
Children with SBM showed reduced magnetic activity in left inferior parietal regions during spoken word recognition and pseudoword reading tasks. We also noted reduced surface area/volume in inferior parietal and posterior temporal regions in SBM and increased gray matter volumes in left middle frontal regions and gyral complexity in left posterior temporal and inferior parietal regions.

CONCLUSIONS:
A complex pattern of changes in cortical morphology and activation may serve as evidence for structural and functional brain reorganization ensuring preservation of language and decoding abilities in children with SBM.

PMID: 21574714

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

Selective and sustained attention in children with spina bifida myelomeningocele

Caspersen ID, Habekost T. (2012) Selective and sustained attention in children with spina bifida myelomeningocele. Child Neuropsychology. 2012 Jan 11.

Spina bifida myelomeningocele (SBM) is a neural tube defect that has been related to deficits in several cognitive domains including attention. Attention function in children with SBM has often been studied using tasks that are confounded by complex motor demands or tasks that do not clearly distinguish perceptual from response-related components of attention. We used a verbal-report paradigm based on the Theory of Visual Attention ( Bundesen, 1990 ) and a new continuous performance test, the Dual Attention to Response Task ( Dockree et al., 2006 ), for measuring parameters of selective and sustained attention in 6 children with SBM and 18 healthy control children. The two tasks had minimal motor demands, were functionally specific and were sensitive to minor deficits. As a group, the children with SBM were significantly less efficient at filtering out irrelevant stimuli. Moreover, they exhibited frequent failures of sustained attention and response control in terms of omission errors, premature responses, and prolonged inhibition responses. All 6 children with SBM showed deficits in one or more parameters of attention; for example, three patients had elevated visual perception thresholds, but large individual variation was evident in their performance patterns, which highlights the relevance of an effective case-based assessment method in this patient group. Overall, the study demonstrates the strengths of a new testing approach for evaluating attention function in children with SBM.


PMID: 22235979

Nonverbal learning disabilities: a critical review.

Spreen O. (2011) Nonverbal learning disabilities: a critical review. Child Neuropsychol. 2011 Sep;17(5):418-43.

This article presents a critical review of the term and concept of nonverbal learning disability (NLD). After a brief historical introduction, the article focuses on the apparent rarity of NLD; the hypothesis of the frequent co-occurrence of emotional disorder, depression, and suicide in NLD; the white matter hypothesis as an explanation of the origin of NLD; and the question of NLD as part of a variety of other disorders. It is argued that NLD presents a broad hypothesis, but that there is little evidence to support its use in clinical practice.



PMID: 21462003

Goal-directed behavior and perception of self-competence in children with spina bifida.

Landry SH, Robinson SS, Copeland D, Garner PW. (1993) Goal-directed behavior and perception of self-competence in children with spina bifida. J Pediatr Psychol. 1993 Jun;18(3):389-96.

Compared a group of school-age children with spina bifida (n = 15) between the ages of 6 and 12 years with an age- and IQ-matched control group of normal children (n = 15). As predicted, the spina bifida children spent less time using goal-directed behaviors and more time in simple manipulation of the toys compared to the normal children. There were no group differences between the spina bifida and normal children's perceived competence but parents of the spina bifida children rated their children as having lower cognitive and physical competence. Associations were found between goal-directed behaviors and perceived self-competence for children in the spina bifida group but not the normal group.

PMID: 8340846

Goal-directed behavior in children with spina bifida.

Landry SH, Copeland D, Lee A, Robinson S. (1990) Goal-directed behavior in children with spina bifida. J Dev Behav Pediatr. 1990 Dec;11(6):306-11.

A group of school-age children with spina bifida (n = 15) between the ages of 6 and 12 years were compared with an age- and IQ-matched control group of normal children (n = 15). Goal-directed behavior in these two groups was measured by videotaped observational measures of the number of different task-oriented play activities the children performed and the amount of time they spent in independent task-oriented activities. Measures of time spent off-task and in simple manipulation of the play materials were taken, as well as the number of social initiations the child directed to the examiner. The children with spina bifida spent less time in task-oriented activities than the control group, even though there were no group differences in the number of activities performed. The differences could not be explained by cognitive impairments or socioeconomic factors. These results suggest that children with spina bifida may have specific problems with sustaining goal-directed behavior, and need assistance in formulating and implementing a sequence of actions in order to achieve concrete short-term goals.

PMID: 2149725

Marital quality of parents of children with spina bifida: a case-comparison study.

Cappelli M, McGarth PJ, Daniels T, Manion I, Schillinger J. (1994) Marital quality of parents of children with spina bifida: a case-comparison study. J Dev Behav Pediatr. 1994 Oct;15(5):320-6.

The impact of childhood chronic illness on parents' marital quality has received limited attention. Most studies have relied solely on mothers' reports and have not examined differences between mothers and fathers. Using a case-control design, this study compared the marital quality within and between dyads of 46 couples with children matched on the age and children matched on the age and sex of the child. During a home visit, parents completed both self-report measures and a communication observational task. Mothers' and fathers' reports of marital quality did not differ between the two groups. Also, no significant differences were found on other marital and psychosocial measures. The most interesting correlations were observed for fathers of children with spinal bifida whose marital quality was associated with parenting stress (r = -.51), depression (r = -.34), and role strain (r = -.34). Overall, the results of this study contribute to the growing body of literature demonstrating that parents of children with a chronic condition are at no greater risk for psychosocial dysfunction, including marital distress, than parents of healthy children. However, to generalize the results, additional research on marital quality with other chronic conditions is required.

PMID: 7868699

Family functioning in children and adolescents with spina bifida: an evidence-based review of research and interventions

Holmbeck GN, Greenley RN, Coakley RM, Greco J, Hagstrom J. (2006) Family functioning in children and adolescents with spina bifida: an evidence-based review of research and interventions.
J Dev Behav Pediatr. 2006 Jun;27(3):249-77.

Research on the adjustment of families of children with spina bifida is reviewed, with a focus on delineating the impact of spina bifida on family functioning, the strengths and weaknesses of past research, and the needs for future evidence-based research on family interventions with this population. PsychINFO and MEDLINE literature searches were used to identify studies of family functioning and family-based interventions for children with spina bifida. Identified studies were empirically evaluated for the presence or absence of key methodological or analytic criteria. Thirty-two studies of family functioning were identified from 25 separate research groups; most studies displayed significant methodological limitations. No published studies of interventions to promote adaptive family functioning were identified. Methodologically sound, longitudinal, and theory-driven studies of family functioning are needed, as are randomized family-based intervention trials to promote adaptive functioning and better psychosocial outcomes in families of children with spina bifida. Specific recommendations for future work as well as clinical implications are noted.

PMID: 16775524

Psychosocial and family functioning in spina bifida.

Holmbeck GN, Devine KA. (2010) Psychosocial and family functioning in spina bifida. Dev Disabil Res Rev. 2010;16(1):40-6.

A developmentally oriented bio-neuropsychosocial model is introduced to explain the variation in family functioning and psychosocial adjustment in youth and young adults with spina bifida (SB). Research on the family functioning and psychosocial adjustment of individuals with SB is reviewed. The findings of past research on families of youth with SB support a resilience-disruption view of family functioning. That is, the presence of a child with SB disrupts normative family functioning but many families adapt to such disruption and exhibit considerable resilience in the face of adversity. Parents of youth with SB, and particularly those from lower socio-economic status (SES) homes, are at-risk for psychosocial difficulties. Individuals with SB are at-risk for developing internalizing symptoms, attention problems, educational difficulties, social maladjustment, and delays in the development of independent functioning. Emerging adults are often delayed in achieving milestones related to this stage of development (e.g., vocational and educational achievements). Methodologically sound, longitudinal, and theory-driven studies of family and psychosocial functioning are needed, as are randomized family-based intervention trials, to promote adaptive functioning and better psychosocial outcomes in families of individuals with SB.

PMID:20419770

Executive functioning and psychological adjustment in children and youth with spina bifida.

Kelly NC, Ammerman RT, Rausch JR, Ris MD, Yeates KO, Oppenheimer SG, Enrile BG. (2011) Executive functioning and psychological adjustment in children and youth with spina bifida. Child Neuropsychol. 2011 Oct 3.


Children and adolescents with spina bifida are at risk for poor neuropsychological functioning and psychological outcomes. The relationship between executive functioning and psychological adjustment is an area worthy of investigation in this population. The current study assessed executive functioning and psychological outcomes in a group of children and adolescents with spina bifida (SBM) (n = 51) and nondisabled controls (n = 45). A mediation model was hypothesized, such that Metacognition, as measured by the Behavior Rating Inventory of Executive Function (BRIEF), mediated the relationship between group status (spina bifida versus nondisabled controls) and psychological outcomes. Results indicated that metacognitive skills fully explained the relationship between group and internalizing and depressive symptoms as reported by mothers. In particular, specific components of the BRIEF Metacognition composite were most responsible for this relationship, including Initiate, Working Memory, and Plan/Organize. The study limitations include its cross-sectional nature that precludes drawing conclusions about causality. The results have implications for treatment interventions for children and adolescents with spina bifida and typically developing individuals.

PMID: 21961993

Expectation of life and unexpected death in open spina bifida: a 40-year complete, non-selective, longitudinal cohort study

Oakeshott P, Hunt GM, Poulton A, Reid F. (2010) Expectation of life and unexpected death in open spina bifida: a 40-year complete, non-selective, longitudinal cohort study Dev Med Child Neurol. 2010 Aug;52(8):749-53.

AIM:
The aim of our study was to investigate survival and causes of death in a complete cohort of open spina bifida at the mean age of 40 years.


METHOD:
We conducted a community-based, prospective study of 117 consecutive infants (50 males, 67 females) with open spina bifida whose backs were closed non-selectively within 48 hours of birth between 1963 and 1971 at Addenbrooke's Hospital, Cambridge, UK. Of those who survived to age 1 year, 89% (82 out of 92) had a cerebrospinal fluid shunt. In 2007, all survivors were surveyed by postal questionnaire backed up by telephone interview. Details of deaths were obtained from the Office for National Statistics, medical records, and autopsy reports, and Kaplan-Meier survival curves were constructed.


RESULTS:
One in three of the cohort (40/117) died before the age of 5 years. A further 26% (31/117) died during the next 35 years, over 10 times the national average. Half the deaths (16/31) after the age of 5 were sudden and unexpected. All occurred in the community and were followed by a coroner's autopsy. The most frequent causes of these unexpected deaths were epilepsy, pulmonary embolus, acute hydrocephalus, and acute renal sepsis. The prognosis for survival was strikingly poor in those with the most extensive neurological deficit. Only 17% (7/42) of those born with a high sensory level (above T11) survived to the mean age of 40 years, compared with 61% (23/38) of those with a low sensory level (below L3; p=0.001).


INTERPRETATION:
Doctors and care planners need to be aware that, contrary to previous suggestions, there is continuing high mortality throughout adult life in individuals with open spina bifida, and many deaths are unexpected.

The Prevalence of Hypertension in Children with Spina Bifida

Mazur L, Lacy B, Wilsford L. (2011) The Prevalence of Hypertension in Children with Spina Bifida Acta Paediatr. 2011 Aug;100(8):e80-3.



AIM:
To determine whether children with spina bifida (SB) have a higher prevalence of hypertension (HTN) than population-based controls.


METHODS:
Charts of all patients (n=123) seen in the Spina Bifida Clinic at Shriners Hospital in Houston, Texas, were reviewed for age, gender, ethnicity, type and level of neural tube defect, height, weight and blood pressure (BP). HTN was defined as a systolic blood pressure or diastolic blood pressure≥95th percentile for age, gender and height on ≥3 occasions. Data from the National Health and Nutrition Examination Survey and from a Houston-based study were used for comparison.


RESULTS:
Fifty-one (41.5%) patients were hypertensive. This was significantly higher than the 3% prevalence in the national controls, p<0.001 and the 4.5% prevalence in the Houston controls, p<0.001. Maximum body mass index increased the risk for HTN [odds ratio, 1.018; 95% confidence interval (1.005, 1.031); and p=0.005].

CONCLUSION:
Children with SB have a significantly higher prevalence of HTN than children in the general population. Age-, gender-, and height-based norms are important for the early identification and treatment of HTN in children.

PMID: 21342248

Neuropsychological Functioning in Early Hydrocephalus: Review From a Developmental Perspective

Erickson K, Baron IS, Fantie BD. (2001) Neuropsychological Functioning in Early Hydrocephalus: Review From a Developmental Perspective Child Neuropsychol. 2001 Dec;7(4):199-229.


Children with hydrocephalus have deficits in several neuropsychological domains. The most notable are motor, visuoperceptual, and visuomotor function. These deficits are multiply determined and depend on the etiology and severity of the hydrocephalus to a large extent. Corpus callosum abnormalities resulting from stretching of callosal fibers and other cortical white matter tracts are implicated as contributory to these deficits. Enlarged ventricles and associated compression of posterior cortical areas also correlate with cognitive impairment. Distinguishing which cognitive domain negatively impacts on the child's functioning and which domains influence behavior in isolation or in combination has been the subject of numerous studies. Developmentally, we know little about the emergence of neuropsychological functioning in children with hydrocephalus. Study of the effects of hydrocephalus at different stages of development is useful to clinicians and researchers interested in the impact of diffuse neurophysiological damage on cognition in the developing brain. The medical and neuropsychological literature have begun to inform about these effects. The core deficits in hydrocephalus have yet to be explicated and a focus on investigations that answer these questions is required. This review summarizes the current knowledge about neurocognitive sequelae of hydrocephalus.

PMID: 16210211

Decreased activation and increased lateralization in brain functioning for selective attention and response inhibition in adolescents with spina bifida.

Ou X, Snow JH, Byerley AK, Hall JJ, Glasier CM. (2011) Decreased activation and increased lateralization in brain functioning for selective attention and response inhibition in adolescents with spina bifida. Child Neuropsychol. 2011 Dec 6.


We used functional magnetic resonance imaging to evaluate functional activity in the brain of adolescents with spina bifida when performing selective attention and response inhibition tasks. We then compared the results to that of age-matched controls. Our results showed that adolescents with spina bifida had decreased frontal and superior parietal activation and more apparently low involvement of left brain hemisphere during these tasks. Our results indicated activation deficits and possibly abnormal functional organization in adolescents with spina bifida and associated pathologies such as hydrocephalus.


PMID: 22145814

Treatment of the neurogenic bladder in spina bifida.

de Jong TP, Chrzan R, Klijn AJ, Dik P. (2008) Treatment of the neurogenic bladder in spina bifida. Pediatr Nephrol. 2008 Jun;23(6):889-96. Review.

Renal damage and renal failure are among the most severe complications of spina bifida. Over the past decades, a comprehensive treatment strategy has been applied that results in minimal renal scaring. In addition, the majority of patients can be dry for urine by the time they go to primary school. To obtain such results, it is mandatory to treat detrusor overactivity from birth onward, as upper urinary tract changes predominantly start in the first months of life. This means that new patients with spina bifida should be treated from birth by clean intermittent catheterization and pharmacological suppression of detrusor overactivity. Urinary tract infections, when present, need aggressive treatment, and in many patients, permanent prophylaxis is indicated. Later in life, therapy can be tailored to urodynamic findings. Children with paralyzed pelvic floor and hence urinary incontinence are routinely offered surgery around the age of 5 years to become dry. Rectus abdominis sling suspension of the bladder neck is the first-choice procedure, with good to excellent results in both male and female patients. In children with detrusor hyperactivity, detrusorectomy can be performed as an alternative for ileocystoplasty provided there is adequate bladder capacity. Wheelchair-bound patients can manage their bladder more easily with a continent catheterizable stoma on top of the bladder. This stoma provides them extra privacy and diminishes parental burden. Bowel management is done by retrograde or antegrade enema therapy. Concerning sexuality, special attention is needed to address expectations of adolescent patients. Sensibility of the glans penis can be restored by surgery in the majority of patients.


PMID: 18350321

Urological follow-up of adult spina bifida patients

Ahmad I, Granitsiotis P. (2007) Urological follow-up of adult spina bifida patients. Neurourol Urodyn. 2007;26(7):978-80. Review.

Department of Urology, Southern General Hospital, Glasgow, Scotland, United Kingdom. imranahmad@doctors.net.uk

AIMS:
The vast majority of the current urological literature understandably has concentrated on the management of children with spina bifida, because in the past the majority did not survive into adulthood. With improvements in the understanding and multidisciplinary care of spina bifida patients it has become a disease of adults. Our aim was to evaluate the current literature to attempt to formulate evidence based guidelines for the management of this difficult group of patients.


METHODS:
We reviewed the literature on adult urological management of spina bifida, all relevant articles which concentrated on adults and long-term management were studied in full.


RESULTS:
Renal function may begin/continue to deteriorate into adulthood, becoming the leading cause of adult death. This is thought to occur because of changes in the adult bladder, with increases in storage pressure. Medical and surgical management should aim to preserve renal function as well as the maintenance of continence in the face of the growing and changing urinary tract. Follow-up should be regular and in the context of a specialist multidisciplinary clinic. Despite being unvalidated in the follow-up of adult spina bifida patient's annual serum creatinine, ultrasound and urodynamics are currently the best tools available.


CONCLUSIONS:
There is no reason why the majority of spina bifida sufferers cannot use their own kidneys for the rest of their lives. This however relies on urological treatment being instigated soon after birth and continuing into adulthood.



PMID: 17626275

Early Start to Therapy Preserves Kidney Function in Spina Bifida Patients

Dik P, Klijn AJ, van Gool JD, de Jong-de Vos van Steenwijk CC, de Jong TP. (2006) Early Start to Therapy Preserves Kidney Function in Spina Bifida Patients
Eur Urol. 2006 May;49(5):908-13. Epub 2006 Jan 19.

OBJECTIVE:
Renal scarring and renal failure remain life-threatening for children born with spinal dysraphism. We reviewed our data of spina bifida patients to evaluate whether optimal treatment of the neurogenic bladder from birth onwards can preserve kidney function.


METHODS:
We reviewed data on all newborns with spinal dysraphism who were referred to our hospital between January 1988 and June 2001. We looked at their situations at referral and at follow-up: the type of treatment, antimuscarinic agents, clean intermittent catheterisation (CIC), antibiotic prophylaxis, and operations (sling procedures, bladder augmentations, antireflux procedures). Renal function (ultrasound, DMSA scan, serum creatinin, creatinin clearance) and bladder function (urodynamic studies) were evaluated over time.


RESULTS:
Data of 144 children of 176 could be evaluated by the end of the study: 5 patients had pre-existing renal abnormalities, 69 had an overactive sphincter, 27 had reflux, and six had renal scarring. None are currently developing end-stage renal disease. All patients with spina bifida aperta started CIC and antimuscarinic therapy shortly after birth. Five of the six patients with renal scarring were started on therapy with intermittent catheterisation and antimuscarinic therapy several months after birth. Sixty-three of 82 children with spina bifida were dry at school age (age six), although 37 of these had not had an operation.


CONCLUSION:
We show that an early start to therapy helps to safeguard renal function for children born with spina bifida. Our data support other recent reports that children born with spina bifida can probably use their own kidneys for a lifetime, if they are given adequate urological treatment. To protect the upper urinary tract, we need to ensure low intravesical pressure by starting children early on CIC (the preferred treatment); antimuscarinic agents to counteract detrusor instability are indispensable in most cases. Proactive treatment of risks for upper tract deterioration results in a negligible loss of renal function, even when early urinary continence is included in the treatment protocol.


PMID:16458416

Care coordination in the spina bifida clinic setting: current practice and future directions

Brustrom J, Thibadeau J, John L, Liesmann J, Rose S. (2012) Care coordination in the spina bifida clinic setting: current practice and future directions.
J Pediatr Health Care. 2012 Jan;26(1):16-26. Epub 2010 Jul 10.

INTRODUCTION:
Although the potential benefits of care coordination are widely recognized, little is known about care coordination in the multidisciplinary spina bifida clinic setting. This study examined several aspects of care coordination in this environment.


METHOD:
We conducted semi-structured interviews with clinic staff (N = 43) and focus groups with caregivers (N = 38) at seven spina bifida clinics in the United States.
RESULTS:

Clinic staff described several primary goals of care coordination, including coordinating multiple services during one visit to ease the burden on families. Although the structure of care coordination varied across the clinics, several clinics had a dedicated care coordinator. Barriers and facilitators to care coordination included staffing issues, clinic day logistics, community resources, and family-related concerns. Despite challenges associated with care coordination processes, clinic staff and caregivers alike believed that care coordination is beneficial.

DISCUSSION:
Study findings suggest ways that care might be coordinated optimally in spina bifida clinics. A synthesis of these findings for clinics interested in implementing care coordination or improving the care coordination services they currently offer is provided.



PMID: 22153140

Academic, Physical, and Social Functioning of Children and Adolescents With Chronic Physical Illness: A Meta-analysis.

Pinquart M, Teubert D. (2011) Academic, Physical, and Social Functioning of Children and Adolescents With Chronic Physical Illness: A Meta-analysis.
J Pediatr Psychol. 2011 Dec 15.

OBJECTIVE:

We compared the levels of academic, physical, and social functioning of children and adolescents with chronic physical diseases with those of healthy peers or test norms.
METHODS:

A random effects meta-analysis was computed to integrate the results of 954 studies.
RESULTS:

Impairments of physical functioning (g = 0.82 standard deviation units) were stronger than impairments of academic (g = 0.53) and social functioning (g = 0.43). Children with cerebral palsy and spina bifida showed the largest levels of functional impairments. The levels of functional impairments also varied by year of publication, source of information, ethnicity, country, and sociodemographic equivalence of the compared groups.
CONCLUSIONS:

More efforts are needed to develop and implement measures for the prevention of impaired functioning of children and adolescents with chronic physical illness and for the reduction of already existing impairments of their functioning.



PMID: 22173882