CSF-Based Analysis for Identification of Potential Serum Biomarkers of Neural Tube Defects.

The protein composition of cerebrospinal fluid (CSF) in neural tube defects (NTDs) remains unknown. We investigated the protein composition of CSF from 9 infants with NTDs using isobaric tags for relative and absolute quantitation (iTRAQ). We identified 568 proteins in the CSF of infants with spina bifida, which is the most common type of NTD. Among these, 18 proteins were associated with neural tube closure in the CSF during human embryonic neurulation and 5 were involved in NTDs. Based on these results, an animal model was further utilized to investigate early serum biomarkers for NTDs. We found that the myristoylated alanine-rich C-kinase substrate, Kunitz-type protease inhibitor 2, and apolipoprotein B-100 protein levels were decreased in both embryos and the sera of pregnant Sprague-Dawley rats carrying embryos with NTDs. CSF proteins may be useful in the discovery of potential serum biomarkers for NTDs.

Neurenteric cyst of the lower clivus.

OBJECTIVE: Neurenteric cysts (NCs) typically arise as benign ventral intradural extramedullary developmental malformations of the spine which contain heterotopic epithelium resembling the intestinal or respiratory tracts. Intracerebral NCs are extremely rare, though the frequency of symptomatic reports and incidental findings is increasing, perhaps because of advances in neuroimaging. Recognition of the unique radiographic and histopathologic features of this entity is of growing importance in the treatment of cysts of the neural axis. We present an unusual case of an NC arising at the lower clivus. CLINICAL PRESENTATION: A 58-year-old man presented with occipitalgia, diplopia, a bilateral hearing deficit, and mild dysphagia. Computed tomography and magnetic resonance imaging demonstrated a 5 x 2 x 3-cm extra-axial cystic midline mass anterior to the brainstem at the lower clivus with posterior cyst wall enhancement. INTERVENTION: The patient underwent a left lateral suboccipital total macroscopic resection of the lesion. Microscopic examination and histopathologic findings were consistent with a diagnosis of NC. CONCLUSION: We describe the clinical presentation, imaging, and histopathologic characteristics, and discuss the diagnosis and surgical treatment of this rare lesion and related pathologic entities. Because of the remote possibility of delayed recurrence, even in cases of apparent total cyst wall removal, long-term serial imaging and a consideration of reoperation for recurrences is advisable.

Caudal block complication in a patient with trisomy 13.

In this report we describe a complication of a caudal block in a 4-year-old child with trisomy 13. The patient's history was remarkable for microcephaly, developmental delay, seizures, apnea, and prolonged emergence times. Induction of anesthesia and tracheal intubation were uneventful. A caudal block was aborted after positive aspiration of cerebrospinal fluid. A radiogram suggestive of spinal dysraphism, found on subsequent review, was confirmed by a magnetic resonance imaging scan consistent with tethered cord and dural ectasia. Congenital abnormalities associated with trisomy 13 and cutaneous signs suggestive of spinal abnormalities are reviewed. Avoidance of neuraxial regional anesthesia in these patients is recommended.

Potential of proton magnetic resonance spectroscopy in the evaluation of patients with tethered cord syndrome following surgery.

OBJECT: Spinal cord dysfunction is associated with an altered neuronal metabolism. The objective of this study is two-fold: 1) to compare pre- and postoperative levels of cerebrospinal fluid (CSF) metabolites in patients with spinal dysraphism and in control patients by performing proton magnetic resonance spectroscopy; and 2) to evaluate the use of magnetic resonance (MR) spectroscopy in the assessment of surgical outcomes in patients with spinal dysraphism. METHODS: The study group population was composed of patients with meningomyeloceles, lipomeningomyeloceles with tethered cord syndrome, and tethered fatty fila. All patients underwent preoperative clinical and neuroimaging (ultrasonography or MR imaging) examinations and MR spectroscopy analysis of metabolites in their CSF. Excision of the neural placode and detethering of a low-lying cord were performed with or without laminectomy. Two months postoperatively, the investigations were repeated. A comparison of pre- and postoperative CSF metabolites was performed using the Wilcoxon signed-rank test and nonparametric tests. Probability values less than 0.05 were considered significant. High levels of lactate (Lac), alanine (Ala), acetate, glycerophosphorylcholine, and choline were observed in the CSF of patients with spinal dysraphism before surgery; after surgery these levels normalized to those observed in control patients. Patients in whom cord retethering occurred could be identified by increased concentrations of Ala and Lac. CONCLUSIONS: The results highlight the potential of MR spectroscopy as a promising tool in the assessment of surgical outcomes in patients with spinal dysraphism.

Levels of soluble adhesion molecules are elevated in the cerebrospinal fluid of children with moyamoya syndrome.

OBJECTIVE: The pathogenesis of moyamoya syndrome is unknown; however, previous studies suggested an inflammatory component. Because adhesion molecules mediate inflammation during cerebral ischemia, we measured the levels of soluble isoforms of the endothelial adhesion molecules vascular cell adhesion molecule Type 1, intercellular adhesion molecule Type 1, and E-selectin in serum and cerebrospinal fluid (CSF) samples from children with moyamoya syndrome. METHODS: Serum and CSF samples were obtained from children with moyamoya syndrome (n = 20) and patients with congenital spinal deformities (n = 20). Soluble vascular cell adhesion molecule Type 1, intercellular adhesion molecule Type 1, and E-selectin levels were measured in enzyme-linked immunoassays. The correlation between the levels of soluble adhesion molecules and the Suzuki angiographic classification was analyzed. CSF/serum albumin index values were also measured, to determine the integrity of the blood-brain barrier. RESULTS: Compared with the control group, children with moyamoya syndrome exhibited significantly elevated CSF levels of soluble vascular cell adhesion molecule Type 1, intercellular adhesion molecule Type 1, and E-selectin. The albumin index for the moyamoya group was 9, which was significantly higher than that for the control group. However, there were no differences in the serum levels of the three soluble adhesion molecules and no correlations between age, Suzuki classification, and serum and CSF levels of adhesion molecules. CONCLUSION: Our study demonstrates increased CSF levels of soluble endothelial adhesion molecules, suggesting that children with moyamoya syndrome have ongoing central nervous system inflammation, with slight impairment of the blood-brain barrier. These soluble adhesion molecules may be clinically useful as indicators of this inflammatory process and may provide some insight into this enigmatic disease process.

The Chiari malformations: a constellation of anomalies.

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.