You-Nam Chung

Elevation of CRABP-I in the Cerebrospinal Fluid of Patients With Moyamoya Disease

Background and Purpose— The etiology of moyamoya disease (MMD) remains obscure. This study was undertaken to identify specific proteins associated with the pathogenesis of MMD. Methods— We studied cerebrospinal fluid (CSF) from 20 patients with angiographically confirmed MMD (4 boys and 16 girls; age range, 3 to 13 years; mean, 7.5 years) and 4 control patients with cerebral palsy who underwent selective dorsal rhizotomy (2 boys and 2 girls; age range, 5 to 10 years; mean, 7.3 years). CSF proteins were analyzed by 2-dimensional polyacrylamide gel electrophoresis, and protein identification was performed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The presence of specific CSF protein in patients with MMD was confirmed by Western blotting. In addition, cerebral CSF was also tested in 7 patients who had other brain diseases but no MMD (2 boys and 5 girls; age range, 1 to 12 years; mean, 6.9 years). Results— We identified 1 polypeptide spot (Mr of 13 to 15 kDa and isoelectric point of 5 to 5.5) that was differentially expressed in the CSF samples of MMD patients (mean optical density intensity, 0.36±0.24; range, 0.05 to 0.92) and control spinal CSF samples (mean, 0.03±0.04; range, 0 to 0.08; P =0.002). This polypeptide was identified as cellular retinoic acid–binding protein (CRABP)-I. High levels of expression of CRABP-I in the CSF from 17 MMD children were confirmed by Western blotting. Conclusions— The analysis of the CSF of MMD patients reveals high CRABP-I expression. The present study suggests that the elevation of CRABP-I in CSF may be a candidate for pathogenesis of MMD.

Shunt Dependency in Shunted Arachnoid Cyst: A Reason to Avoid Shunting

Cystoperitoneal (CP) shunting is minimally invasive and achieves a high rate of resolution on neuroimaging. However, in the absence of definite symptoms, shunting should be reconsidered, because some patients can experience shunt dependency after CP shunting. In this study, the risk of shunt dependency in patients with arachnoid cysts treated with CP shunting and the management of these patients are described. Eight patients (7 boys and 1 girl) were diagnosed as shunt dependent following CP shunting. At the time of the first operation (mean age at first shunting 6.1 years, range 1–11 years), a causal relationship between symptoms and the arachnoid cyst was evident in only 2 cases. Clinical manifestations, neuroimaging (computed tomography and/or magnetic resonance imaging) and intracranial pressure (ICP) data were reviewed retrospectively. The mean age of the patients at the time of shunt dependency was 9.8 years (range 6–13 years), and the mean time between the first shunt operation and shunt dependency was 41 months (range 17–80 months). Although neuroimaging demonstrated a collapsed cyst and small ventricles in most patients, ICP monitoring revealed significant intracranial hypertension. The release of shunt ligation, revision or additional shunting, such as ventriculoperitoneal shunting or lumboperitoneal shunting, resulted in the complete resolution of symptoms except in one patient who lost vision. This study shows that shunt dependency after CP shunting is a real problem and requires more attention. ICP monitoring can demonstrate the presence of intracranial hypertension when clinical and radiological analyses do not.

Clinical analysis of vertebrobasilar dissection

SummaryBackground. The natural history of vertebrobasilar artery dissection (VAD) is not fully known. The purpose of this study was to review the clinical outcome of the patients with VAD, then to propose an appropriate management strategy for VAD.Method. From 1992 to 2004, 35 VAD patients admitted to our institutes were retrospectively reviewed. There were 28 men and 7 women, whose age ranged from 4 to 67 years with a mean age of 44 years. Angiography was assessed to document the shape, and location of the dissecting aneurysm with respect to the posterior inferior cerebellar artery (PICA). A modified Rankin score was assigned for functional outcome. The functional outcome scores were analyzed according to the patient’s age, gender, hypertension history, the pattern of initial manifestation, angiographic shape of VAD, angiographic location of VAD, treatment modality.Findings. There was no statistically significant difference between the functional outcome with age, gender, trauma history and past medical history of hypertension. Of 35 patients, 22 presented with SAH, 11 with ischemic symptoms and 2 were incidentally detected. The patients without SAH had a better functional outcome than those with SAH (p = 0.029). There was statistical significance between Hunt–Hess (H–H) grade and clinical outcome (p = 0.032). The shape and location of VAD was not significantly related to the functional outcome (p = 0.294, 0.840). But all the cases of rebleeding and mortality (except one case with initially poor H–H grade) developed exclusively in patients with aneurysms. There was no statistically significant correlation between the treatment modality and the outcome (p = 0.691).Conclusion. The VAD patients with SAH would be recommended to be managed by either surgical or endovascular treatment, but those without SAH, could be managed conservatively with antiplatelet therapy and/or anticoagulation.

Transsphenoidal Microsurgery for Pediatric Craniopharyngioma: Special Considerations Regarding Indications and Method

Although the transsphenoidal approach offers a narrow operative field and poor visual control through a small sellar opening, this approach has the advantage of being associated with minimal surgical trauma, especially in children. We share our experience of good surgical outcome achieved by the transsphenoidal approach in selected craniopharyngiomas in childhood, and report on our pediatric series of transsphenoidal complete removals of six relatively large craniopharyngiomas and one Rathke’s cleft cyst. The most common presenting symptom was visual dysfunction (6/7). All tumors were ‘prechiasmatic’ cystic masses with moderate to marked suprasellar extensions and elevated diaphragm sellae. The tumors measured from 25 to 37 mm in maximum diameter in the midsagittal plane (median 33 mm). In 5 of the 7 tumors, the suprasellar portion (range 11–27 mm) was larger than the intrasellar portion (range 8–14 mm). Gross total resection was achieved in all patients. Special attention should be paid to multicystic craniopharyngiomas to prevent the possibility of incomplete tumor resection. The ‘bone in a fat pocket’ method was useful for preventing postoperative cerebrospinal fluid leakage. Vision was improved in all six patients who had preoperative visual disturbances. Hypopituitarism was provoked by radical tumor removal in all patients and managed by hormonal supplementation therapy. Transsphenoidal surgery is an appropriate approach for the radical excision of intrasellar-suprasellar ‘prechiasmatic’ craniopharyngiomas, even in children, and even if the tumor has a relatively large suprasellar component.

Gene expression profile analyses of cortical dysplasia by cDNA arrays

Cortical dysplasia (CD) is a well-recognized cause of intractable epilepsy, especially in children and is characterized histologically by derangements in cortical development and organization. The objective of this study was to expand the current knowledge of altered gene expression in CD as a first step towards in the identification of additional genes operative in the evolution of CD. Surgical specimens were obtained from eight patients (4 males and 4 females; age range 2-38 years; mean 15 years) with a pathologic diagnosis of CD. Nondysplastic temporal neocortex was obtained from a 2-year-old boy with intractable epilepsy and medial temporal lobe ganglioglioma. After total RNA isolation from frozen brain tissues, we carried out gene expression profiling using a cDNA expression array. Differences in gene expressions between CD and the nondysplastic neocortex were confirmed by semi-quantitative conventional reverse transcription-PCR. Three genes (recombination activating gene 1 (RAG1), heat shock 60 kDa protein 1 (HSP-60), and transforming growth factor beta1 (TGF beta1)) were found to be up-regulated more than two-fold in CD, whereas four genes (phosphoinositide-3-kinase regulatory subunit polypeptide 1 [p85 alpha] (PI3K), frizzled homolog 2 [Drosophila], Bcl-2/adenovirus E1B 19 kDa interacting protein (NIP3), and glia maturation factor beta (GMF beta)) were down-regulated to less than 50% of their normal levels. Interestingly, the majority of genes showing altered expression were associated with apoptosis. Our study demonstrates diverse changes in gene expression in CD. However, it remains to be shown which of these are causally related to the evolution of CD.

Spinal intramedullary lipoma: report of three cases

Study design: Case report.Objective: To report three cases of spinal intramedullary lipoma seen in the last 10 years and present the clinical characteristics and surgical outcome of these cases.Method: Two patients were boys aged 12 years and 7 months, respectively. The other was a female patient aged 6 months. Chief complaints were hemiparesis, back swelling and thoracic scoliosis. All patients were diagnosed with magnetic resonance images. The lesion was located in the cervico-thoracic spine (foramen magnum to T1) in one case, thoracic spine (T9−T12) with the back swelling at L2-4 level in the second, and in the third, one mass extended from C6 to T11 and the other mass was located in the L1-2 level, separately.Result: All masses were removed subtotally and dysraphism was absent. Postoperatively, neurological status of the first and the second patient were unchanged, but in the third case weakness was transiently aggravated.Conclusion: Intramedullary lipoma is a rare spinal lesion and multiple intramedullary lipoma is extremely rare. Treatment principle is surgical decompression before symptom progression. Laminoplastic laminotomy is an appropriate approach for decompression of an intramedullary lipoma.

Enhancement of re-closure capacity by the intra-amniotic injection of human embryonic stem cells in surgically induced spinal open neural tube defects in chick embryos.

To evaluate the re-closure promoting capacity of human embryonic stem (hES) cells injected into the amniotic cavity on spinal open neural tube defects (ONTDs) of chick embryos, neural tubes were opened at Hamburger and Hamilton stage 18 or 19 and the embryos were divided into three groups: a control group (no injection), a vehicle group, and a hES cell group (injection of 20,000 hES cells immediately after neural tube incision). On postoperative days 3, 5, and 7, ONTDs were significantly more re-closed in the hES cell group than in the other two groups. hES cells were present at the area in the process of re-closure, and covered ONTDs, but were not found in the re-closed area, suggesting indirect effects rather than cell replacement on the neural tissue.

Expression of neuronal markers in the secondary neurulation of chick embryos.

ObjectiveThe goal of our study was to evaluate the expression patterns of neuronal antigens during the process of secondary neurulation.Materials and methodsChick embryos of Hamburger and Hamilton stages 16, 18, 20, 22, 24, 26, 30, 35, 40, and 45 were harvested, and tail sections were processed for neuronal antigen studies.Results and conclusionsThe areas and periods showing positive reactions for each antigen are as follows: neuronal cell adhesion molecule (N-CAM): the secondary neural tube and notochord from stages 18 to 26 and the germinal and mantle layers from stages 30 to 45; synaptophysin: the caudal cell mass, secondary neural tube, and notochord from stages 22 to 26, the germinal and mantle layers from stages 30 to 45, and the marginal layer at the later stages of development; neurofilament-associated protein (3A10): the dorsal white matter, dorsal root ganglion, and scattered cells around the germinal layer from stages 35 to 45; and neuronal nuclear-specific protein (NeuN): the mantle layer at stage 35, which shows decreased reaction at stages 40 and 45; islet-1: no remarkable staining on the caudal cell mass or on the other neural structures at all stages. Our results indicate that neuronal markers of the secondary neurulation in chick embryos have their own chronological patterns of expression. At early stages of secondary neurulation, N-CAM and synaptophysin are thought to modulate the differentiation of structures derived from the caudal cell mass. At later stages, N-CAM, synaptophysin, 3A10, and NeuN seem to be involved in the maturation of the caudal spinal cord.

Identification of patients with childhood moyamoya diseases showing temporary hypertension after anesthesia by preoperative multifractal Hurst analysis of heart rate variability.

OBJECTIVE This study was performed to determine whether the preoperative multifractal Hurst analysis of heart rate variability might identify and characterize childhood patients with moyamoya disease (MMD) who showed temporary postoperative hypertension. METHODS We studied 59 childhood patients with MMD. Thirty were classified as hypertensive group when the mean arterial pressure in the postoperative recovery room was 120% or greater than that during the preoperative period and 29 were classified as normotensive group. The 2 groups were compared with respect to preoperative indices of heart rate variability including frequency-domain measures, approximate entropy, and very short-term multifractal Hurst exponents of RR intervals (RRI). Using preoperative indices that showed significant differences, discriminant analysis was performed to identify postoperative hypertensive patients. RESULTS Only exponents of the order > or =3 (H3alpha, H4alpha, and H5alpha) were significantly lower in the hypertensive group than in the normotensive group. Frequency-domain measures, approximate entropy, and the exponents of the order < or =2 were not significantly different in the 2 groups. Discriminant analysis using all of the three exponents correctly identified 27/30 (90%) of the postoperative hypertensive patients. CONCLUSIONS Preoperative very short-term multifractal Hurst analysis of RRI variability identified 90% of childhood MMD patients who developed postoperative hypertension. The preoperative characteristic of RRI variability was the reduced smoothness at the 8-second-long, local RRI regions within which a very large change of RRI occurs.

Expression of neuronal antigens and related ventral and dorsal proteins in the normal spinal cord and a surgically induced open neural tube defect of the spine in chick embryos: an immunohistochemical study

ObjectiveThe aims of this study were to elucidate the processes of neuronal differentiation and ventrodorsal patterning in the spinal cord of the chick embryo from embryonic day (E) 3 to E17 and to study the effect of a prenatal spinal open neural tube defect (ONTD) on these processes.MethodExpression patterns of neuronal antigens (neuronal nuclear antigen, neurofilament-associated protein (NAP), and synaptophysin) and related ventral markers [sonic hedgehog, paired box gene (PAX)6, and islet-1], and dorsal markers (bone morphogenetic protein, Notch homolog 1, and PAX7) were investigated in the normal spinal cord and in a surgically induced spinal ONTD in chick embryos. Four normal and ONTD chick embryos were used for each antigen group.Result & ConclusionThere were no differences in the expression of neuronal and ventrodorsal markers between the control and ONTD groups. NAP and synaptophysin were useful for identifying dorsal structures in the distorted anatomy of the ONTD chicks.