Seung Chyul Hong

Clinical and biological implications of CD133-positive and CD133-negative cells in glioblastomas

A number of recent reports have demonstrated that only CD133-positive cancer cells of glioblastoma multiforme (GBM) have tumor-initiating potential. These findings raise an attractive hypothesis that GBMs can be cured by eradicating CD133-positive cancer stem cells (CSCs), which are a small portion of GBM cells. However, as GBMs are known to possess various genetic alterations, GBMs might harbor heterogeneous CSCs with different genetic alterations. Here, we compared the clinical characteristics of two GBM patient groups divided according to CD133-positive cell ratios. The CD133-low GBMs showed more invasive growth and gene expression profiles characteristic of mesenchymal or proliferative subtypes, whereas the CD133-high GBMs showed features of cortical and well-demarcated tumors and gene expressions typical of proneuronal subtype. Both CD133-positive and CD133-negative cells purified from four out of six GBM patients produced typical GBM tumor masses in NOD-SCID brains, whereas brain mass from CD133-negative cells showed more proliferative and angiogenic features compared to that from CD133-positive cells. Our results suggest, in contrast to previous reports that only CD133-positive cells of GBMs can initiate tumor formation in vivo CD133-negative cells also possess tumor-initiating potential, which is indicative of complexity in the identification of cancer cells for therapeutic targeting.

Extratemporal hypometabolism on FDG PET in temporal lobe epilepsy as a predictor of seizure outcome after temporal lobectomy

We investigated the relationship between the presence of extratemporal hypometabolism on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) and seizure outcome after temporal lobectomy in patients with medically intractable temporal lobe epilepsy (TLE). In 47 patients with intractable unilateral mesial TLE, regional metabolic changes on FDG PET images obtained during the 2 months preceding anterior temporal lobectomy were compared with postoperative seizure outcome. Postoperative seizure outcome was evaluated with a mean follow-up period of 6.1±0.6 years (range 5.2−7.2 years). Forty-two (89%) of the 47 patients achieved a good postoperative seizure outcome (Engel class I or II). All patients had hypometabolism in the temporal cortex ipsilateral to the epileptogenic region on FDG PET scans. Fourteen (78%) of the 18 patients with hypometabolism only in the ipsilateral temporal cortex were completely seizure free (Engel class Ia) after surgery. In contrast, five (45%) of the 11 patients with extratemporal cortical hypometabolism confined to the ipsilateral cerebral hemisphere and only four (22%) of the 18 patients with hypometabolism in the contralateral cerebral cortex were completely seizure free after surgery. The postoperative seizure-free rates were significantly different across the three groups of patients with different cortical metabolic patterns (P<0.005). Furthermore, all of the nine patients with a non-class I outcome (Engel class II−IV) had extratemporal (including contralateral temporal) cortical hypometabolism. Thalamic hypometabolism was noted in 20 (43%) of the 47 patients (ipsilateral in 12, bilateral in 8). Sixteen (59%) of the 27 patients with normal thalamic metabolism were completely seizure free after surgery, while only seven (35%) of the 20 patients with thalamic hypometabolism became completely seizure free (P<0.05). Multivariate analysis revealed that among variables including clinical, EEG, magnetic resonance imaging, pathological and FDG PET metabolic findings, only cortical metabolic pattern was an independent factor for the prediction of postoperative seizure outcome (P<0.005). It is concluded that extratemporal cortical hypometabolism outside the seizure focus, in particular hypometabolism in the contralateral cerebral cortex, may be associated with a poorer postoperative seizure outcome in TLE and may represent underlying pathology that is potentially epileptogenic. Thalamic hypometabolism, which was associated, but not independently, with a higher likelihood of postoperative seizures, may be secondary to extratemporal or temporal pathology.

Regional Cerebral Hyperperfusion with Ictal Dystonic Posturing: Ictal–Interictal SPECT Subtraction

Summary:u2003 Purpose: Ictal–interictal single‐photon emission computed tomography (SPECT) subtraction was performed to find brain structures related to ictal dystonic posturing (DP) in patients with temporal lobe epilepsy (TLE).

Combined Temporal and Frontal Epileptogenic Foci in Meningioangiomatosis

Meningioangiomatosis (MA), a rare hamartomatous lesion, can be seen in neurofibromatosis type 2 but may occur as an isolated abnormality [1]. The tumor involves the frontal or temporal cortices in 90% of the cases [2]. Symptomatic cases usually present with a long history of seizures [1, 3, 4]. Wiebe et al. [1] reported a spectrum of electrophysiologic findings in MA, based primarily on scalp EEG and intraoperative interictal ECoG. Epileptic foci in tumor cases may arise not only in the adjacent cortex but also within the tumor itself or occasionally far from the lesion [1, 5–8]. We studied epileptogenic foci in an intractable epilepsy patient with medial frontal MA.

Interaction between the electrical stimulation of a face-selective area and the perception of face stimuli

We electrically stimulated the face-selective area in epileptic patients while they were performing a face-categorization task. Face categorization was interfered by electrical stimulation but was restored by increasing the visual signal. More importantly, face-categorization interference by electrical stimulation was confined to face-selective electrodes, and the amount of interference was positively correlated with the sensitivity of the face-selective electrodes. These results strongly support the hypothesis that the face-selective area has a direct causal link to face perception.

Determinants of Basal Collaterals in Moyamoya Disease: Clinical and Genetic Factors

Background/Aims: To enable the diagnosis of moyamoya disease (MMD), detection of distal internal carotid artery stenosis and hazy network of basal collaterals (BCs) are required. This study aimed at evaluating the factors that could determine the degree of BCs in patients with angiographically confirmed MMD. Methods: We analyzed 146 consecutive patients with MMD (age 26.2 ± 19.6, range 1-75). The degree of BCs (%) was measured based on conventional angiography. Factors associated with the degree of BCs, including clinico-radiological and genetic factors (p.Arg4810Lys variant), were analyzed. Results: The degree of BCs varied among MMD patients and significantly decreased with an increase in the age of diagnosis of MMD (coefficient -1.55; p < 0.001). Although the degree of BC development depends on the MMD stage (Suzuki stage), it is less prominent in adult-onset (>18 years) MMD compared to childhood MMD. The presence of p.Arg4810Lys variant, types of MMD (bilateral vs. unilateral) and stroke (ischemic, hemorrhagic, or asymptomatic), shrinkage (outer diameter) of intracranial vessels, external carotid collateral status, and cortical neovascularization were not associated with the degree of BCs. Conclusion: Although prominent BCs are required for diagnosis of MMD, BCs are decreased with aging, suggesting that angiogenic capacity is altered in adult onset MMD compared to childhood MMD.

Frequency and significance of rare RNF213 variants in patients with adult moyamoya disease

Purpose Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by stenosis of the internal carotid arteries with compensatory development of collateral vessels. Although a founder variant of RNF213, p.Arg4810Lys (c.14429G>A, rs112735431), is a major genetic risk factor for MMD in East Asians, the frequency and disease susceptibility of other variants in this gene remain largely unknown. In the present study, we investigated the association of RNF213 variants with MMD in Korean patients and population controls. Methods For all RNF213 variants listed in the Human Gene Mutation Database (HGMD) as disease-causing or likely disease-causing mutations for MMD, genotyping was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Genetic data from 264 adult patients with MMD were analyzed and compared with two control populations comprised of 622 and 1,100 Korean individuals, respectively. Results Among the 30 RNF213 variants that were listed in the HGMD, p.Arg4810Lys was identified in 67.4% (178/264) of patients with MMD and showed a significantly higher allele frequency than in the controls, giving an odds ratio of 63.29 (95% confidence interval, 33.11–120.98) for the 622 controls and 48.55 (95% confidence interval, 31.00–76.03) for the 1100 controls. One additional variant, p.Ala5021Val (c.15062C>T, rs138130613), was identified in 0.8% (2/264) of patients; however, the allele frequencies were not significantly different from those in the controls. Conclusions These results suggest that, in our cohort of Korean patients, the p.Arg4810Lys is the only variant that is strongly associated with MMD among the 30 RNF213 variants listed in the HGMD.

Safety and efficacy of antiplatelet response assay and drug adjustment in coil embolization: a propensity score analysis

IntroductionThe purpose of this study was to explore the safety and efficacy of an antiplatelet response assay and drug adjustment to prevent delayed thromboembolic events after stent-assisted coil embolization.MethodsA total of 370 patients were enrolled in this study between December 2005 and July 2014. Of these, 124 patients were placed into the drug resistance test (DRT) group with drug adjustment according to response to an antiplatelet agent, and 246 patients comprised the control group with a standard antiplatelet regimen. The response to the antiplatelet agent was evaluated with the VerifyNow Rapid Platelet Function Assay. Propensity score matching analysis was performed with one-to-multiple matching.ResultsAmong 370 patients, delayed thromboembolic events occurred in 28 (7.6xa0%) patients including 25 (10.2xa0%) in the control group and three (2.4xa0%) in the DRT group. Antiplatelet response test (pxa0=xa00.012), diabetes mellitus (DM) (pxa0=xa00.014), and hypertension (HTN) (pxa0<xa00.001) were associated with delayed infarction in multivariate analysis. In propensity score matching analysis, 331 patients were matched (control group (nxa0=xa0229) vs. DRT group (nxa0=xa0103)), and antiplatelet response (hazard ratio 0.247, 95xa0% confidence interval 0.070–0.868, pxa0=xa00.029) was correlated with delayed infarction. Conversely, the two groups were not significantly different with regard to total (pxa0=xa00.368) or major hemorrhagic complications (pxa0=xa00.108).ConclusionAntiplatelet drug adjustment according to the results of an antiplatelet response assay might be associated with a decreased risk of delayed thromboembolic infarction compared with the standard antiplatelet regimen.

Morphological risk factors for the rupture of anterior communicating artery aneurysms: the significance of fenestration.

IntroductionThe purpose of this study was to evaluate morphological factors associated with rupture in anterior communicating artery (AcomA) aneurysms and to investigate the significance of AcomA fenestration as a risk factor for aneurysm rupture.MethodsThe clinical and radiologic findings of 255 patients with AcomA aneurysms treated with coil embolization between January 2005 and March 2014 were retrospectively reviewed. We performed univariate and multivariate analyses to evaluate the associations between morphological variables and rupture status.ResultsThe number of patients with AcomA fenestration was 17 out of 255 (6.6xa0%). There were no statistically significant differences between the fenestration group and non-fenestration group in clinical and morphological characteristics. Multivariate logistic regression tests showed that superior direction of aneurysm dome (OR 2.802, pu2009=u20090.023), presence of a bleb (OR 5.998, pu2009<u20090.001), high aspect ratio (OR 3.138, pu2009=u20090.009), size greater than 7xa0mm (OR 3.356, pu2009=u20090.013), and AcomA fenestration (OR 4.135, pu2009=u20090.026) were significantly associated with AcomA aneurysm rupture.ConclusionsThe results of this study demonstrated that a fenestrated AcomA is associated with risk of aneurysm rupture. Therefore, AcomA fenestration can be considered as an important morphological risk factor for rupture, along with other known risk factors such as the direction of aneurysm dome, a bleb, high aspect ratio, and size.

Spontaneous angiographic changes in venous drainage patterns related to symptom changes in patients with untreated cavernous sinus dural arteriovenous fistula

IntroductionWe evaluated the relationship between symptomatic and angiographic changes in untreated cavernous sinus dural arteriovenous fistulas (CSdAVFs), focusing on venous drainage patterns.MethodsThe clinical and radiologic features of 34 cases of untreated CSdAVF were retrospectively reviewed. We classified venous drainage patterns as type I (only antegrade drainage), type II (combined antegrade drainage and venous reflux), type III (venous reflux without antegrade drainage), or type IV (stasis or occlusion of venous reflux). Symptom changes were categorized as improvement, aggravation of initial symptoms, or symptom pattern change.ResultsTwenty-one patients (61xa0%) showed symptom changes during follow-up (median, 12; range, 3–151xa0months). In the symptom improvement group (nu2009=u200910), patients who underwent follow-up angiography (nu2009=u20094) exhibited spontaneous occlusion. In the symptom aggravation group (nu2009=u20094), new venous reflux developed in 2 patients (type I to type II) and spontaneous occlusion in 2 patients (type III to spontaneous occlusion). In the symptom pattern change group (nu2009=u20097), 2 patients showed new venous reflux (type I to type II), and 5 showed stasis or occlusion of an engorged ophthalmic vein (type II or III to type IV). Angiographic regression was observed in all type III and IV patients, and cortical venous reflux (CVR) developed in 1 type I patient.ConclusionSymptom changes correlated with chronological angiographic changes. Without treatment, most CSdAVFs behaved benignly and had a low incidence of CVR. Therefore, close observation is a possible protocol for managing CSdAVFs that have tolerable symptoms, no CVR, and no antegrade drainage despite aggravation or fluctuation in symptoms.