Tackeun Kim

Moyamoya Disease: Treatment and Outcomes

Although the pathogenesis of moyamoya disease (MMD) has not been fully elucidated, the effectiveness of surgical revascularization in preventing stroke has been addressed by many studies. The main mechanism of surgical revascularization is augmenting the intracranial blood flow using an external carotid system by either direct bypass or pial synangiosis. This can improve resting cerebral blood flow as well as vascular reserve capacity. For direct revascularization, the superficial temporal artery is used as the donor artery in most cases, although the occipital artery may be used in limited cases. Usually, the cortical branch of the middle cerebral artery is selected as the recipient of direct anastomosis. As for indirect revascularization, various techniques using different kinds of connective tissues have been introduced. In some cases, reinforcing the anterior cerebral artery and the posterior cerebral artery territories can be considered. The effectiveness of surgical revascularization for preventing ischemic stroke had been generally accepted by many studies. However, for preventing hemorrhagic stroke, new evidence has been added by a recent randomized controlled trial. The incidence of peri-operative complications such as stroke and hyperperfusion syndrome seems to be high due to the nature of the disease and technical demands for treatment. Preventing and adequately managing these complications are essential for ensuring the benefits of surgery.

Stroke prevention by direct revascularization for patients with adult-onset moyamoya disease presenting with ischemia

OBJECT Moyamoya disease (MMD) is a progressive disease that can cause recurrent stroke. The authors undertook this retrospective case-control study with a large sample size in an attempt to assess the efficacy of direct or combined revascularization surgery for ischemia in adults with MMD. METHODS The authors investigated cases involving patients with moyamoya disease presenting with ischemia who visited Seoul National University Bundang Hospital and Seoul National University Hospital between 2000 and 2014. Among 441 eligible patients, 301 underwent revascularization surgery and 140 were treated conservatively. Variables evaluated included age at diagnosis, sex, surgical record, Suzuki stage, and occurrence of stroke. Patients were stratified into 2 groups based on whether or not they had undergone revascularization surgery. Actuarial 1-, 5-, and 10-year stroke rates were calculated using the life table method. Risk factor analysis for 5-year stroke occurrence was conducted with multivariate regression. RESULTS Of the 441 patients, 301 had been surgically treated (revascularization group) and 140 had not (control group). The mean follow-up durations were 45 and 77 months, respectively. The actuarial 10-year cumulative incidence rate for any kind of stroke was significantly lower in the revascularization group (9.4%) than in the control group (19.6%) (p = 0.041); the relative risk reduction (RRR) was also superior (52.0%) in the revascularization group, and the number needed to treat was 10. The 10-year rate of ischemic stroke was greater (13.3%) in the control group than in the revascularization group (3.9%) (p = 0.019). The RRR for ischemic stroke in the revascularization group was 70.7%, and the number needed to treat was 11. However, the actuarial 1- and 5-year rates of ischemic stroke did not significantly differently between the groups. Overall, revascularization surgery was shown to be an independent protective factor, as revealed by multivariate analysis. CONCLUSIONS Direct or combined revascularization for patients with adult-onset moyamoya disease presenting with ischemia can prevent further stroke.

Survival benefit of levetiracetam in patients treated with concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide for glioblastoma multiforme.

A chemosensitizing effect of levetiracetam (LEV) has been suggested because LEV inhibits O‐6 methylguanine‐DNA methyltransferase (MGMT). However, the survival benefit of LEV has not been clinically documented. The objective of this study was to assess the survival benefit of LEV compared with other antiepileptic drugs as a chemosensitizer to temozolomide for patients with glioblastoma.

Epidemiology of Moyamoya Disease in Korea: Based on National Health Insurance Service Data

There have been a few studies reporting the epidemiology of moyamoya disease in Korea. Previous studies revealed relatively high prevalence and incidence of moyamoya disease in Korea and Japan. This study was designed to provide the latest epidemiologic information of moyamoya disease in Korea. We analyzed a database comprising of 50 million people covered in Korea by the National Health Insurance Service to calculate the prevalence. The incidence was estimated by eliminating the duplicated records of previous 3 years. We summarized the prevalence and incidence according to age, sex, and local distribution. In addition, the chronological changes were demonstrated with direct standardization using the 2010 population structure information. The standardized prevalence was 6.5 per 100000 persons in 2005, which was increased to 18.1 in 2013. In the same period, standardized incidence was increased from 2.7 to 4.3 per 100000 persons. The prevalence for men was 4.9 and 8.3 for women in 2005. In 2013, the prevalence had increased for men and women to 13.8 and 25.3, respectively. The incidence for men and women was 2.2 and 3.2, respectively, in 2005. It had increased to 3.5 and 5.7, respectively. The mean age of patients was 33.5 in 2005 and increased to 42.5 in 2013. The peak prevalent age group had shifted slightly to the older age groups, with chronologically consistent female predominance. The prevalence was highest in Jeollabuk province and lowest in Ulsan city.

Risk Factor Analysis for the Recurrence of Chronic Subdural Hematoma: A Review of 368 Consecutive Surgical Cases

Objective Chronic subdural hematoma (CSDH) is a common form of extra axial hemorrhage in the elderly. A surgical procedures such as a burr hole trephination are used for the CSDH treatment. The recurrence rate of CSDH is reported to range from 2.3 to 33%. In the current study, we focused on the determination of risk factors associated with the recurrence of CSDH. Methods We retrospectively reviewed 368 consecutive patients with CSDH treated by burr hole trephination. Univariate and multivariate analysis were performed to describe the relationships between clinical and radiological factors as well as the recurrence of CSDH. Results Totally 31 (8.4%) patients experienced a recurrence of CSDH in our study. The male group (10.2%) had a higher recurrence rate than the female group (3.1%). Also patients with malignant neoplasm history showed a high recurrence rate (17.9%). The recurrence rate of single layer CSDH (13.1%) and isodensity CSDH (11.7%) was highly significant also. Conclusion Sex, history of malignant neoplasm and the hematoma type on computed tomography were factors related with the recurrence of CSDH in our study. These findings may be supportive in the identification of patients at risk for a recurrence of CSDH.

The incidence of and risk factors for ischemic complications after microsurgical clipping of unruptured middle cerebral artery aneurysms and the efficacy of intraoperative monitoring of somatosensory evoked potentials: A retrospective study

OBJECTIVES Ischemic complications (ICs) account for 6.7% after microsurgical clipping of unruptured intracranial aneurysms. This study aimed to evaluate the efficacy of somatosensory evoked potential (SSEP) monitoring during microsurgical clipping of unruptured middle cerebral artery (MCA) aneurysms and evaluate the incidence of and risk factors for ischemic complications after clipping of unruptured MCA aneurysms. PATIENTS AND METHODS Herein, 1208 patients with cerebral aneurysms and treated with microsurgical clipping between May 2003 and February 2015 were enrolled. Those with multiple aneurysms, history of head trauma, subarachnoid hemorrhage, bypass and/or endovascular treatment, and intraoperative rupture were excluded. Subsequently, 411 patients with single unruptured MCA aneurysms treated with simple microsurgical clipping were enrolled. Patients were divided into two groups based on the application of SSEP monitoring during surgery. RESULTS The IC rate was 0.9% and 5.6% in the SSEP and non-SSEP groups, respectively. Univariate analysis revealed that age≥62.5years, aneurysm size≥4.15mm, temporary clipping, history of hyperlipidemia and stroke, and no-SSEP monitoring were risk factors for ICs. Multivariate logistic regression analysis showed that age≥62.5years (odds ratio [OR]=7.7; 95% confidence interval [95% CI]=1.5-37.7; P=0.011), previous stroke (OR=26.8, 95% CI=2.4-289.2, P=0.007), and inversely SSEP monitoring (OR=0.14, 95% CI 0.02-0.72, P=0.019) were independent risk factors for ICs. CONCLUSION Clinicians should consider the possibility of IC during microsurgical clipping of unruptured MCA aneurysms in patient≥62.5years and/or a history of stroke. Intraoperative SSEP monitoring is an effective and feasible tool for preventing IC.

Association between moyamoya syndrome and the RNF213 c.14576G>A variant in patients with neurofibromatosis Type 1

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.

Incidence and risk factors of intracranial aneurysm: A national cohort study in Korea

Background Estimations of the intracranial aneurysm incidence require long-term follow-up of a relatively large at-risk population; as a result, the incidence remains largely unknown. Aims To investigate the national incidence of intracranial aneurysm in a Korean population. Methods After excluding 18,604 potential subjects with a previous history of stroke (I6x.x), 998,216 subjects were included in this observational cohort. The primary endpoint was the earliest date of diagnosis of either unruptured intracranial aneurysm (UIA; I67.1) or subarachnoid hemorrhage (SAH; I60.x). We collected anthropometric data, blood pressure measurements, laboratory data, and smoking, drinking, and physical exercise habits of 132,355 subjects for whom healthcare screening data were available. Factors influencing intracranial aneurysm were evaluated via multivariate Cox regression. Results The overall observation size was 8,792,214 person-years. During follow-up, 4346 subjects were diagnosed with intracranial aneurysm (SAH, 1960; UIA, 2386). The crude incidence of intracranial aneurysm was 49.4/100,000 person-years. The hazard ratio for women was 1.56 (p < 0.01), and older subjects had an increased hazard ratio. Subjects with hypertension had an approximately 1.5-fold higher risk of intracranial aneurysm. A history of heart disease and family history of stroke were associated with respective hazard ratios of 2.08 and 1.77. Conclusions In this Korean population study, the standardized incidence of intracranial aneurysm was 52.2/100,000 person-years. Older age, female sex, hypertension, history of heart disease, and family history of stroke were independent risk factors for intracranial aneurysm.

Prophylactic Antiplatelet Medication in Endovascular Treatment of Intracranial Aneurysms: Low-Dose Prasugrel versus Clopidogrel.

BACKGROUND AND PURPOSE: Prophylactic antiplatelet medication is beneficial in decreasing thromboembolic complications during endovascular treatment of unruptured intracranial aneurysms. The efficacy may be limited by variability of individual response to antiplatelet medication, especially clopidogrel. We compared the efficacy of 2 antiplatelet medications, low-dose prasugrel and clopidogrel, in patients undergoing endovascular treatment of unruptured aneurysms. MATERIALS AND METHODS: From November 2014 to July 2015, 194 patients with a total of 222 unruptured aneurysms underwent endovascular treatment at a single institution. Laboratory and clinical data from the prospectively maintained registry were used in this study. Antiplatelet medication was given the day before endovascular treatment (prasugrel 20 mg or 30 mg or clopidogrel 300 mg). Response to the antiplatelet medication was measured by the VerifyNow system. Periprocedural adverse event rates between the 2 groups were compared. RESULTS: There were no significant differences in the baseline characteristics of patients and aneurysms between the 2 groups. The P2Y12 reaction unit values were lower (clopidogrel group versus prasugrel group, 242.7 ± 69.8 vs 125.7 ± 79.4; P < .0001) and percentage inhibition values were higher (22.1% ± 19.7% vs 60.2 ± 24.7%; P < .0001) in the prasugrel group. There were no thromboembolic events, but there was 1 procedural bleed in each group, without any clinical consequences. CONCLUSIONS: The prasugrel group showed more effective and consistent platelet inhibition. We may omit the antiplatelet response assay with the low-dose prasugrel premedication before the endovascular treatment of patients with unruptured aneurysms. Further study is required to determine whether there is benefit of this strategy regarding clinical outcome.

Intracranial Stenting Using a Drug-Eluting Stent for Moyamoya Disease Involving Supraclinoid ICA: A Case Report

A 43-year-old woman was diagnosed with moyamoya disease (MMD) and underwent right-side bypass surgery. After surgery, previous symptoms disappeared. One month later, transient right hemiparetic attacks and motor dysphasia developed. Angiography revealed progressive severe stenosis of left supraclinoid segment of internal carotid artery. Angioplasty using a drug-eluting stent (DES) was performed. For 18 months, she presented no ischemic symptom and no in-stent stenosis was observed in follow-up angiography. This is the first case report about effect of DES use for MMD. Considering that intimal hyperplasia is a pathophysiology of stenosis, DES may have a role in reducing progression of stenosis in selected moyamoya patients.