Metabolite Profile of Cerebrospinal Fluid in Patients With Spina Bifida: A Proton Magnetic Resonance Spectroscopy Study

Pal, Kamalesh; Sharma, Uma; Gupta, Devendra K.; Pratap, Akshay; Jagannathan, N. R.

doi:10.1097/01.brs.0000152161.08313.04

Cited by 17 publications

(16 citation statements)

References 35 publications

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“…However, our results are consistent with studies of CSF in humans and in animal model studies of hydrocephalus, which itself results in tissue displacement, disruption, demyelination, and elimination of certain pathways 17,19,56. In the absence of comparisons with other origins of congenital hydrocephalus (such as aqueductal stenosis, which is even more rare than SB, and a cohort for which we did not sample), we cannot show that these findings are specific to SB or that they reflect more than the effects of hydrocephalus.…”

Section: Discussionsupporting

confidence: 91%

“…The present study includes a relatively small number of patients that prevents analysis of relevant treatment factors (such as shunt placement) and we lack histological analyses using CSF metabolite analysis and postmortem data that would directly address the DT imaging–derived hypotheses about neuropathology 19,56. However, our results are consistent with studies of CSF in humans and in animal model studies of hydrocephalus, which itself results in tissue displacement, disruption, demyelination, and elimination of certain pathways 17,19,56.…”

Section: Discussionmentioning

confidence: 99%

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Quantitative diffusion tensor imaging and intellectual outcomes in spina bifida

Hasan

Sankar

Halphen

et al. 2008

PED

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Object Patients with spina bifida (SB) have variable intellectual outcomes. The authors used diffusion tensor (DT) imaging to quantify whole-brain volumes of gray matter, white matter, and cerebrospinal fluid (CSF), and perform regional quantitative microstructural assessments of gray matter nuclei and white matter tracts in relation to intellectual outcomes in patients with SB. Methods Twenty-nine children with myelomeningoceles and 20 age- and sex-matched children with normal neural tube development underwent MR imaging with DT image acquisition and assessments of intelligence. The DT imaging–derived metrics were the fractional anisotropy (FA), axial (parallel), and transverse (perpendicular) diffusivities. These metrics were also used to segment the brain into white matter, gray matter, and CSF. A region-of-interest analysis was conducted of the white and gray matter structures implicated in hydrocephalus. Results The amount of whole-brain gray matter was decreased in patients with SB, with a corresponding increase in CSF (p < 0.0001). Regional transverse diffusivity in the caudate nucleus was decreased (p < 0.0001), and the corresponding FA was increased (p < 0.0001), suggesting reduced dendritic branching and connectivity. Fractional anisotropy in the posterior limb of the internal capsule increased in the myelomeningocele group (p = 0.02), suggesting elimination of some divergent fascicles; in contrast, the FA in several white matter structures (such as the corpus callosum genu [p < 0.001] and arcuate fasciculus) was reduced, suggesting disruption of myelination. Diffusion tensor imaging–metrics involving gray matter volume and the caudate nucleus, but not other structures, predicted variations in IQ (r = 0.37–0.50; p < 0.05). Conclusions Diffusion tensor imaging–derived metrics provide noninvasive neuronal surrogate markers of the pathogenesis of SB and predict variations in general intellectual outcomes in children with this condition.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Quantitative diffusion tensor imaging and intellectual outcomes in spina bifida

Hasan

Sankar

Halphen

et al. 2008

PED

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“…1 shows a typical two-dimensional [ 13 C, 1 H] HSQC spectrum of metabolites extracted from the human breast cancer cells. The assignment of 13 C-1 H cross peaks for various metabolites was made by comparing the carbon and proton chemical shifts with literature values (12)(13)(14)(15)(16)(17), with spectra of pure compounds and by spiking the samples. Overall, 24 metabolites could be unambiguously assigned.…”

Section: C-isotopomer Modelmentioning

confidence: 99%

Comparative Metabolomics of Breast Cancer

Yang

Richardson²,

Smith³

et al. 2006

Biocomputing 2007

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Comparative metabolic profiling of cancerous and normal cells improves our understanding of the fundamental mechanisms of tumorigenesis and opens new opportunities in target and drug discovery. Here we report a novel methodology of comparative metabolome analysis integrating the information about both metabolite pools and fluxes associated with a large number of key metabolic pathways in model cancer and normal cell lines. The data were acquired using [U-13 C]glucose labeling followed by two-dimensional NMR and GC-MS techniques and analyzed using isotopomer modeling approach. Significant differences revealed between breast cancer and normal human mammary epithelial cell lines are consistent with previously reported phenomena such as upregulation of fatty acid synthesis. Additional changes established for the first time in this study expand a remarkable picture of global metabolic rewiring associated with tumorigenesis and point to new potential diagnostic and therapeutic targets.

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“…The observed association between MMP‐8 and lactic acid levels suggests that hypoxic conditions are elevated in the amniotic cavity as a consequence of an open spinal defect. Lactic acid, the major by‐product of glycogen metabolism in an anaerobic environment, has been shown to be present at elevated levels in amniotic fluid as well as in spinal fluid from fetuses with spina bifida compared with fetuses with normal neurological development. There is a precedent for an elevation in MMP production under hypoxic conditions.…”

Section: Discussionmentioning

confidence: 99%