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Eun Ju Lee, Hyun Joo Lee, Min Kyung Hyun, Ji Eun Choi, Jong Hee Kim, Na Rae Lee, Jin Seub Hwang and Jin-Won Kwon

Object

The authors investigated the rupture rate among patients with untreated unruptured intracranial aneurysms (UIAs) in South Korea during 2006–2009.

Methods

A longitudinal study using national representative health-claim data, including all hospital records for every Korean citizen, was used. Patients with a UIA who were 18–80 years old in 2006 were identified using the I67.1 ICD-10 code. To select eligible patients, a historical period of 1 year prior to the first diagnosis of a UIA in 2006 was utilized. Patients with a previous UIA diagnosis, subarachnoid hemorrhage (SAH), or treatments, such as clipping or coiling, during the historical period were excluded from analysis. Patients with head trauma or a brain tumor during the historical period were also excluded. Eligible patients were followed up for at least 3 years from the index date. Rupture was defined as SAH events with at least 14 days of hospitalization, using the I60 ICD-10 code and excluding the I60.8 code, or death within 14 days of hospitalization.

Results

Seven thousand four hundred four patients with UIAs were identified, including 1441 treated patients (20%) and 5963 untreated patients (80%), with a median follow-up of 3.3 years. Rupture events occurred in 163 (0.9 cases/100 person-years) of the 5963 untreated patients. The rupture rate was highest in the 1st year after UIA diagnosis. An older age was a risk factor for rupture among patients with UIAs.

Conclusions

The overview of the incidence of rupture indicates the need for a preventive strategy and future studies to prevent rupture in Asian patients with UIAs.

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Jung Hee Kim, Yun-Sik Dho, Yong Hwy Kim, Jung Hyun Lee, Ji Hyun Lee, A. Ram Hong and Chan Soo Shin

OBJECTIVE

The natural history and proper algorithm for follow-up testing of nonfunctioning pituitary adenomas (PAs) are not well known, despite their relatively high prevalence. The aim of this study was to suggest the optimal follow-up algorithm for nonfunctioning PAs based on their natural history.

METHODS

The authors followed up 197 patients with nonfunctioning PAs that had not been treated (including surgery and radiation therapy) at the time of detection, in a single center, between March 2000 and February 2017. They conducted a hormone test, visual field test, and MRI at the time of diagnosis and yearly thereafter.

RESULTS

The overall median follow-up duration was 37 months. Microadenomas (n = 38) did not cause visual disturbance, pituitary apoplexy, or endocrine dysfunction. The incidence of patients with tumor volume growth ≥ 20% was higher for macroadenomas than microadenomas (13.8 vs 5.0 per 100 person-years [PYs], p = 0.002). The median time to any tumor growth was 4.8 years (95% CI 3.4–4.8 years) for microadenomas and 4 years (95% CI 3.3–4.2 years) for macroadenomas. The overall incidence of worsening visual function was 0.69 per 100 PYs. Patients with a tumor volume growth rate ≥ 0.88 cm3/year (n = 20) had a higher incidence of worsening visual function (4.69 vs 0.30 per 100 PYs, p < 0.001). The tumor growth rate of all microadenomas was < 0.88 cm3/year. The median time to tumor growth ≥ 20% was 3.3 years (95% CI 1.8–3.9 years) in patients with a tumor growth rate ≥ 0.88 cm3/year and 4.9 years (95% CI 4.6–7.2 years) in patients with a tumor growth rate < 0.88 cm3/year.

CONCLUSIONS

The authors have devised a follow-up strategy based on the tumor volume growth rate as well as initial tumor volume. In patients with microadenomas, the next MRI study can be performed at 3 years. In patients with macroadenomas, the second MRI study should be performed between 6 months and 1 year to assess the tumor growth rate. In patients with a tumor growth rate ≥ 0.88 cm3/year, the MRI study should be performed within 2 years. In patients with a tumor growth rate < 0.88 cm3/year, the MRI study can be delayed until 4 years.

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Hyun-Seung Kang, Youn-Joo Moon, Young-Yim Kim, Woong-Yang Park, Ae Kyung Park, Kyu-Chang Wang, Jeong Eun Kim, Ji Hoon Phi, Ji Yeoun Lee and Seung-Ki Kim

Object

Moyamoya disease (MMD) is a cerebrovascular occlusive disease affecting bilateral internal carotid termini. Smooth-muscle cells are one of the major cell types involved in this disease process. The characteristics of circulating smooth-muscle progenitor cells (SPCs) in MMD are poorly understood. The authors purified SPCs from the peripheral blood of patients with MMD and sought to identify differentially expressed genes (DEGs) in SPCs from these patients.

Methods

The authors cultured and isolated SPCs from the peripheral blood of patients with MMD (n = 25) and healthy control volunteers (n = 22). After confirmation of the cellular phenotype, RNA was extracted from the cells and DEGs were identified using a commercially available gene chip. Real-time quantitative reverse transcription polymerase chain reaction was performed to confirm the putative pathogenetic DEGs.

Results

The SPC-type outgrowth cells in patients with MMD invariably showed a hill-and-valley appearance under microscopic examination, and demonstrated high α–smooth muscle actin, myosin heavy chain, and calponin expression (96.5% ± 2.1%, 42.8% ± 18.6%, and 87.1% ± 8.2%, respectively), and minimal CD31 expression (less than 1%) on fluorescence-activated cell sorter analysis. The SPCs in the MMD group tended to make more irregularly arranged and thickened tubules on the tube formation assay. In the SPCs from patients with MMD, 286 genes (124 upregulated and 162 downregulated) were differentially expressed; they were related to cell adhesion, cell migration, immune response, and vascular development.

Conclusions

With adequate culture conditions, SPCs could be established from the peripheral blood of patients with MMD. These cells showed specific DEGs compared with healthy control volunteers. This study provides a novel experimental cell model for further research of MMD.

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Jun Hyong Ahn, Ji Hoon Phi, Hyun-Seung Kang, Kyu-Chang Wang, Byung-Kyu Cho, Ji Yeoun Lee, Gi Beom Kim and Seung-Ki Kim

This 13-month-old boy, in whom Kawasaki disease had been diagnosed at the age of 6 months, presented with subarachnoid hemorrhage caused by the rupture of a middle cerebral artery aneurysm. The authors performed an emergency craniectomy and clip occlusion of the aneurysm, which was found to be partially thrombosed. The patient was discharged 4 weeks postoperatively without apparent neurological deficit.

Intracranial saccular aneurysms in the pediatric population are rare, and are occasionally associated with various systemic disorders. Kawasaki disease is a systemic vasculopathy of unknown origin, but cerebral arteries are usually spared from the disease process. This is the second case report of a ruptured cerebral aneurysm in a patient with Kawasaki disease, providing a novel clinical feature that the authors call Kawasaki syndrome.

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Jung Won Choi, Sung Min Son, Inhee Mook-Jung, Youn Joo Moon, Ji Yeoun Lee, Kyu-Chang Wang, Hyun-Seung Kang, Ji Hoon Phi, Seung Ah Choi, Sangjoon Chong, Jayoung Byun and Seung-Ki Kim

OBJECTIVE

Moyamoya disease (MMD) is a unique cerebrovascular disorder characterized by the progressive occlusion of the bilateral internal carotid arteries. Endothelial colony-forming cells (ECFCs), previously termed “endothelial progenitor cells,” play an important role in the pathogenesis of MMD. In this study, the authors performed morphological and functional studies of the mitochondria of ECFCs from patients with MMD to present new insights into the pathogenesis of the disease.

METHODS

The morphology of ECFCs from 5 MMD patients and 5 healthy controls was examined under both a transmission electron microscope and a confocal laser scanning microscope. The oxygen consumption rates (OCRs), mitochondrial membrane potentials (MMPs), intracellular Ca2+ concentrations, mitochondrial enzyme activities, and reactive oxygen species (ROS) levels were measured. Functional activity of the ECFCs was evaluated using a capillary tube formation assay.

RESULTS

The ECFCs from the MMD patients displayed a disrupted mitochondrial morphology, including a shorter and more circular shape. The ECFC mitochondria from the MMD patients exhibited functional abnormalities, which were assessed as a decreased OCR and an increased intracellular Ca2+ concentration. Moreover, the ECFCs from MMD patients showed increased ROS levels. Interestingly, treatment with an ROS scavenger not only reversed the mitochondrial abnormalities but also restored the angiogenic activity of the ECFCs from the MMD patients.

CONCLUSIONS

The mitochondria of ECFCs from MMD patients, as compared with those from healthy patients, exhibited morphological and functional abnormalities. This finding suggests that the mitochondrial abnormalities may have a role in the pathogenesis of MMD.

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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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Min A. Yoon, Eunhee Kim, Bae-Ju Kwon, Jeong Eun Kim, Hyun-Seung Kang, Jae Hyo Park, Chul-Ho Sohn, Ji-Hoon Kim and Dong Hoon Lee

Object

Reinforcement of aneurysms with additional wrapping is an alternative procedure if the aneurysm cannot be completely clipped. Wrapping with muslin (cotton gauze) rarely incites foreign body inflammatory reactions. In this study, the authors describe the clinical and radiological features of muslinomas or muslin-induced foreign body reactions that can develop after treatment of intracranial aneurysms.

Methods

Over a 3-year period, 5 patients with muslinomas underwent treatment at the authors' institution. All patients underwent aneursym clipping and wrapping, and were subsequently readmitted with acute or subacute neurological symptoms. Clinical and imaging features on diffusion weighted MR images and cerebral angiography images were retrospectively reviewed. The patients' clinical course and follow-up imaging studies were also evaluated.

Results

In all 5 cases, muslinomas were seen as rim-enhancing inflammatory masses around the clipped aneurysms with perilesional edema visible on MR images at the time of clinical deterioration. The MR images also demonstrated adhesive arachnoiditis with a sterile intracranial abscess in 3 patients, optic neuropathy in 2, parent artery narrowing in 2, and a resultant acute ischemic infarction in 1 patient. Follow-up imaging revealed resolution of both the perilesional edema and adhesive arachnoiditis but no significant changes in the muslinomas. All patients underwent conservative management and fully recovered, but during the follow-up period, 2 patients experienced clinical and radiological relapses.

Conclusions

When a patient with a history of wrapping of an aneurysm presents with acute neurological symptoms and an enhancing intracranial mass in the region of the surgical site on MR imaging, a muslin-induced foreign body inflammatory reaction should be considered in the differential diagnosis, and careful clinical and radiological follow-up is advised.