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Seung Ah Choi, Sangjoon Chong, Pil Ae Kwak, Youn Joo Moon, Anshika Jangra, Ji Hoon Phi, Ji Yeoun Lee, Sung-Hye Park, and Seung-Ki Kim

OBJECTIVE

Endothelial colony-forming cells (ECFCs) isolated from pediatric patients with moyamoya disease (MMD) have demonstrated decreased numbers and defective functioning in in vitro experiments. However, the function of ECFCs has not been evaluated using in vivo animal models. In this study, the authors compared normal and MMD ECFCs using a chronic cerebral hypoperfusion (CCH) rat model.

METHODS

A CCH rat model was made via ligation of the bilateral common carotid arteries (2-vessel occlusion [2-VO]). The rats were divided into three experimental groups: vehicle-treated (n = 8), normal ECFC-treated (n = 8), and MMD ECFC-treated (n = 8). ECFCs were injected into the cisterna magna. A laser Doppler flowmeter was used to evaluate cerebral blood flow, and a radial arm maze test was used to examine cognitive function. Neuropathological examinations of the hippocampus and agranular cortex were performed using hematoxylin and eosin and Luxol fast blue staining in addition to immunofluorescence with CD31, von Willebrand factor, NeuN, myelin basic protein, glial fibrillary acidic protein, and cleaved caspase-3 antibodies.

RESULTS

The normal ECFC-treated group exhibited improvement in the restoration of cerebral perfusion and in behavior compared with the vehicle-treated and MMD ECFC-treated groups at the 12-week follow-up after the 2-VO surgery. The normal ECFC-treated group showed a greater amount of neovasculogenesis and neurogenesis, with less apoptosis, than the other groups.

CONCLUSIONS

These results support the impaired functional recovery of MMD ECFCs compared with normal ECFCs in a CCH rat model. This in vivo study suggests the functional role of ECFCs in the pathogenesis of MMD.

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Hyeoncheol Hwang, Kyu-Chang Wang, Moon Suk Bang, Hyung-Ik Shin, Seung-Ki Kim, Ji Hoon Phi, Ji Yeoun Lee, Jinwoo Choi, Seungwoo Cha, and Keewon Kim

OBJECTIVE

The aim of this study was to establish optimal electric stimulation parameters for intraoperatively monitoring the bulbocavernosus reflexes (BCRs) in infants.

METHODS

The authors retrospectively reviewed the medical records of all infants (age < 24 months) who had undergone an untethering operation for tethered cord syndrome between May 2013 and February 2014 at a single institution and whose baseline BCR had been elicited during surgery. Using different combinations of stimulation parameters—number of stimulation pulses: 4 or 8 pulses, interpulse interval: 1, 2, or 5 msec, and polarity of stimulation: biphasic or monophasic—the authors compared the relative mean amplitude of 10 BCR responses (rmaBCRs) to each combination of parameters.

RESULTS

The rmaBCRs were larger with the 8-pulse stimulations than with the 4-pulse stimulations (p < 0.0001). There was a tendency, though not statistically significant, for larger rmaBCRs to be obtained with the longer interpulse interval in the 8-pulse stimulation (p = 0.1289). The biphasic stimulation produced larger rmaBCRs than the monophasic stimulation (p = 0.0005).

CONCLUSIONS

Biphasic 8-pulse stimulations with 5-msec or 2-msec intervals yield the largest BCR responses. Considering that an 8-pulse stimulation with 5-msec intervals may overlap the onset of the BCR, a biphasic 8-pulse stimulation with 2-msec intervals is recommended as the optimal stimulation paradigm to monitor intraoperative BCRs in infants.

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Ji Yeoun Lee, Young Ah Lee, Hae Woon Jung, Sangjoon Chong, Ji Hoon Phi, Seung-Ki Kim, Choong-Ho Shin, and Kyu-Chang Wang

OBJECTIVE

Due to their distinct location, suprasellar arachnoid cysts are known to cause a wide variety of problems, such as hydrocephalus, endocrine symptoms, and visual abnormalities. The long-term outcome of these cysts has not been elucidated. To find out the long-term outcome of suprasellar arachnoid cysts, a retrospective review of the patients was performed. The neurological and endocrine symptoms were thoroughly reviewed.

METHODS

Forty-five patients with suprasellar arachnoid cysts, with an average follow-up duration of 9.7 years, were enrolled in the study. A comprehensive review was performed of the results of follow-up regarding not only neurological symptoms but also endocrine status. The outcomes of 8 patients who did not undergo operations and were asymptomatic or had symptoms unrelated to the cyst were included in the series.

RESULTS

Surgery was most effective for the symptoms related to hydrocephalus (improvement in 32 of 32), but endocrine symptoms persisted after surgery (4 of 4) and required further medical management. More surprisingly, a fairly large number of patients (14 of 40; 1 was excluded because no pre- or postoperative endocrine evaluation was available) who had not shown endocrine symptoms at the time of the initial diagnosis and treatment later developed endocrine abnormalities such as precocious puberty and growth hormone deficiency. The patients with endocrine symptoms detected during the follow-up included those in both the operated (n = 12 of 32) and nonoperated (n = 2 of 8) groups who had been stable during follow-up since the initial diagnosis.

CONCLUSIONS

This study implies that patients with suprasellar arachnoid cysts can develop late endocrine problems during follow-up, even if other symptoms related to the cyst have been successfully treated. Hence, patients with these cysts need long-term follow-up for not only neurological symptoms but also endocrine abnormalities.

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Haeng Jin Lee, Ji Hoon Phi, Seung-Ki Kim, Kyu-Chang Wang, and Seong-Joon Kim

OBJECTIVE

The aim of this study was to report the incidence of and the factors associated with papilledema in children with hydrocephalus.

METHODS

Patients younger than 15 years of age who had been diagnosed with hydrocephalus and treated by extra-ventricular drainage or ventriculoperitoneal shunt surgery between 2005 and 2015 were retrospectively reviewed. Factors including patient age and sex, etiology of hydrocephalus, duration of signs or symptoms, intracranial pressure (ICP), and presence of papilledema were evaluated.

RESULTS

Forty-six patients, whose mean age was 6.3 ± 4.7 years, were included in the study. The 19 patients without papilledema had a mean age of 2.7 ± 2.7 years, and the 27 patients with papilledema had a mean age of 8.8 ± 4.2 years (p < 0.001). The mean ICP was 19.9 ± 10.0 cm H2O among those without papilledema and 33.3 ± 9.1 cm H2O among those with papilledema (p < 0.001). The mean duration of signs or symptoms was 3.0 ± 4.6 months in the patients without papilledema and 3.4 ± 3.9 months in those with papilledema (p = 0.704). The patients with papilledema were older and presented with higher ICP than those without. The causes of hydrocephalus were tumor (59%), congenital anomaly (19%), hemorrhage (13%), and infection (9%).

CONCLUSIONS

Papilledema was more common in patients who were older, who had higher ICP, and whose hydrocephalus had been induced by brain tumor. However, since papilledema was absent in 41% of the children with hydrocephalus, papilledema's absence does not ensure the absence of hydrocephalus, especially in younger patients.

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Ji Hoon Phi, Jung Won Choi, Moon-Woo Seong, Tackeun Kim, Youn Joo Moon, Joongyub Lee, Eun Jung Koh, Seul Ki Ryu, Tae Hee Kang, Jae Seung Bang, Chang Wan Oh, Sung Sup Park, Ji Yeoun Lee, Kyu-Chang Wang, and Seung-Ki Kim

OBJECTIVE

In a minority of patients with neurofibromatosis Type 1 (NF-1), cerebral vasculopathy reminiscent of moyamoya disease develops. This phenomenon is called moyamoya syndrome (MMS), but there are no known risk factors for the prediction of MMS in NF-1 patients. Polymorphism of the RNF213 gene has exhibited strong associations with familial and sporadic moyamoya disease and other cerebral vasculopathies. The aim of this study is to find whether the RNF213 c.14576G>A variant is associated with MMS development in the NF-1 population or not.

METHODS

The MMS group included 16 NF-1 patients with documented MMS. The control group consisted of 97 NF-1 patients without MMS. Genomic DNA samples were obtained from the saliva or blood of both groups, and the presence of the RNF213 c.14576G>A variant was assessed by Sanger sequencing.

RESULTS

In the MMS group, 3 patients had the RNF213 c.14576G>A variant (18.7%), whereas no patients with this genetic variation were observed in the control group (0%). There was a meaningful association between the RNF213 c.14576G>A variant and MMS development (p = 0.0024). The crude odds ratio was calculated as 50.57 (95% CI 1.57–1624.41). All 3 patients with MMS and the c.14576G>A variant were diagnosed with MMS at an early age and had bilateral involvement.

CONCLUSIONS

The RNF213 c.14576G>A variant is more common in NF-1 patients who develop MMS than in NF-1 patients without MMS. This variant might be a susceptibility gene for the NF-1–moyamoya connection.

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Jung Won Choi, Seung-Ki Kim, Kyu-Chang Wang, Ji Yeoun Lee, Jung-Eun Cheon, and Ji Hoon Phi

Object

Ventriculoperitoneal (VP) shunt surgery is the most common treatment for hydrocephalus. In certain situations, uncommon complications can occur after shunting procedures. The authors undertook this study to analyze the clinical characteristics of pediatric patients who developed multifocal intraparenchymal hemorrhages (MIPHs) as a complication of shunt surgery. The authors also analyzed the risk factors for MIPH in a large cohort of patients with hydrocephalus.

Methods

This study included all pediatric patients (age < 18 years) who underwent VP shunt surgery at the authors' institution between January 2001 and December 2012. During this period, 507 VP shunt operations were performed in 330 patients. Four of these patients were subsequently diagnosed as having MIPH. The authors analyzed the clinical characteristics of these patients in comparison with those of the entire group of shunt-treated patients.

Results

The incidence of MIPH was 1.2% (4 of 330 cases) for all pediatric patients who underwent VP shunt placement but 2.9% (4 of 140 cases) for infants less than 1 year old. When the analysis was limited to patients whose corrected age was less than 3 months, the incidence was 5.3% (4 of 76 cases). Of the 4 patients with MIPH, 2 were male and 2 were female. Their median age at surgery was 54 days (range 25–127 days), and in all 4 cases, the patients' corrected age was less than 1 month. Three patients were preterm infants, whereas one patient was full-term. None of these patients had a prior history of intracranial surgery (including CSF diversion procedures). All showed severe hydrocephalus during the preoperative period. Their clinical courses as patients with MIPH were comparatively favorable, despite the radiological findings.

Conclusions

MIPH is a rare but not negligible complication of VP shunt surgery. This complication might be a unique phenomenon in infants, especially young, preterm infants with severe hydrocephalus. Moreover, the absence of previous intracranial procedures might be one of the risk factors for this complication. The rapid alteration of brain conditions in the setting of immaturity might cause MIPH. To prevent this complication, the authors recommend that pressure settings of programmable valves should be gradually adapted to the target pressure.

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Byung Chan Lim, Jong Hee Chae, Seung-Ki Kim, Sung-Hye Park, Kyu-Chang Wang, Ji Yeoun Lee, and Ji Hoon Phi

Brainstem glioma is a highly devastating disease, and any mass-like lesion in the brainstem can raise suspicion of this diagnosis. However, other inflammatory, demyelinating, or degenerative diseases can mimic brainstem glioma in clinical presentation and imaging features. Therefore, diagnosis based solely on imaging is often insufficient for brainstem lesions and may lead to incorrect diagnosis and treatment.

This case report is the first description of central nervous system aquaporin-4 (AQP4) autoimmunity confined mainly to the brainstem. It demonstrates the wide spectrum of neuroinflammatory diseases in children and highlights the utility of surgical biopsy for suspicious brainstem lesions with atypical imaging features for glioma.

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Jung Won Choi, Ji Yeoun Lee, Ji Hoon Phi, Kyu-Chang Wang, Hyun-Tai Chung, Sun Ha Paek, Dong Gyu Kim, Sung-Hye Park, and Seung-Ki Kim

Object

Neurofibromatosis Type 2 (NF2) is an autosomal-dominant inherited disease, characterized by multiple neoplasia syndromes, including meningioma, schwannoma, glioma, and ependymoma. In this report, the authors present their clinical experience with pediatric NF2 patients. In particular, they focused on the clinical course of vestibular schwannoma (VS), including the natural growth rate, tumor control, and functional hearing outcomes.

Methods

From May 1988 to June 2012, the authors recruited patients who were younger than 18 years and fulfilled the Manchester criteria. In total, 25 patients were enrolled in this study. The authors analyzed the clinical course of these patients. In addition, they measured the natural growth rate of VS before any treatment in these children with NF2. Then, they evaluated the tumor control rate and functional hearing outcomes after the treatment of VS.

Results

The mean age at the onset of NF2-related symptoms was 9.9 ± 4.5 years (mean ± SD, range 1–17 years). The mean age at the diagnosis of NF2 was 12.9 ± 2.9 years (range 5–17 years). The mean follow-up period was 89.3 months (range 12–311 months). As initial manifestations, nonvestibular symptoms were frequently observed in pediatric patients with NF2. The mean natural growth rate of VS was 0.33 ± 0.41 cm3/year (range 0–1.35 cm3/year). The tumor control rate of VS was 35.3% at 3 years after Gamma Knife surgery (GKS). The actuarial rate of useful hearing preservation was 67% in the 1st year and 53% in the 5th year after GKS.

Conclusions

Clinical manifestations in children with NF2 were highly variable, compared with their adult counterparts. The natural growth rate of VS in children is slow, and this oncological feature may explain the diverse clinical manifestations besides vestibular symptoms in children with NF2. The treatment outcome of GKS for VS in children with NF2 was not favorable compared with previous reports of affected adults.

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Hyunho Choi, Ji Yeoun Lee, Ji Hoon Phi, Seung-Ki Kim, Byung-Kyu Cho, and Kyu-Chang Wang

Object

Postoperative epidural hematoma (EDH), a blood collection between the inserted galeal flap and the overlying skull flap (epigaleal flap hematoma), is a frustrating complication of the surgical treatment of moyamoya disease (MMD) in pediatric patients. The symptoms of postoperative EDH are often similar to those of postoperative cerebral ischemia, and may cause confusion during clinical decision making. The authors designed this study to evaluate the incidence, clinical presentation, risk factors, and treatment outcomes of postoperative EDH in pediatric patients with MMD.

Methods

A retrospective review of 148 pediatric patients with 250 craniotomies who underwent indirect bypass revascularization surgery between January 2002 and December 2006 was performed. This group consisted of 60 male and 88 female patients, and the mean age at surgery was 7.5 years (range 1–18 years).

Results

Of the 250 craniotomies, postoperative EDH was detected in 32 cases. In 12 cases of EDH, surgical treatment was necessary (4.8% of 250 craniotomies). During the same period, 743 non-MMD craniotomy operations were performed. In 6 of these 743 operations, patients developed postoperative EDH that required surgical treatment, significantly less than the percentage of EDH requiring postoperative treatment in patients with MMD (0.8%, p < 0.001). The average interval between craniotomy surgery and the detection of EDH was 1.8 days (range 0–5 days) in patients with MMD and 0.5 days (range 0–2 days; p = 0.018) in the non-MMD craniotomy group.

Postoperative EDH was observed in significantly fewer cases (17 of 191) when a subcutaneous drain (SCD) was inserted over the bone flap than in cases in which an SCD was not inserted (14 of 55; p = 0.001). The mean international normalized ratio of prothrombin time in the immediate postoperative blood test was 1.27 ± 0.17 in the EDH group and 1.20 ± 0.11 in the non-EDH group (values are expressed as the mean ± SD; p = 0.008). Central galeal flap tenting suture and immediate postoperative platelet count were not related to the incidence of postoperative EDH following pediatric MMD surgery.

Conclusions

Postoperative EDH is more likely to be found following craniotomy in patients with MMD than in those without MMD, and may occur in a delayed fashion. Insertion of an SCD and immediate correction of an abnormal value for international normalized ratio of prothrombin time can decrease the incidence of postoperative EDH following surgery for pediatric MMD.