Je Young Yeon

Supratentorial cavernous angiomas presenting with seizures: Surgical outcomes in 60 consecutive patients

The aim of this study is to determine surgical outcomes and factors affecting seizure outcomes in patients who harbor supratentorial cavernous angiomas presenting with seizures. Sixty patients were classified into the intractable epilepsy group (n=22) and the sporadic seizure group (n=38) and then managed differently in accordance with our guidelines. Patients exhibiting sporadic seizures were treated by lesionectomy, except for patients harboring mesial temporal lesions. We performed lesionectomy, extended lesionectomy, standard temporal lobectomy and tailored resection on 33, 9, 9 and 9 patients, respectively. Finally, 72.7% (16/22) of patients with intractable epilepsy and 89.5% (34/38) of patients with sporadic seizures achieved Engel Class I outcomes. A long duration of illness was somewhat related to a poor outcome in patients with intractable epilepsy, yet this was not true of patients with sporadic seizures. Other factors which included age at onset, size of the lesions and locations were not related to seizure outcomes. The role of residual hemosiderin is yet to be discovered. A lesionectomy alone can be considered a reasonable approach for those patients who exhibit sporadic seizures and have an extra-temporal or neo-temporal lesion. In patients with intractable epilepsy and/or mesial temporal lesions, a more invasive approach could achieve the better seizure outcome.

Adult Moyamoya Disease: A Burden of Intracranial Stenosis in East Asians?

Background Both Moyamoya disease (MMD) and intracranial atherosclerotic stenosis (ICAS) are more prevalent in Asians than in Westerners. We hypothesized that a substantial proportion of patients with adult-onset MMD were misclassified as having ICAS, which may in part explain the high prevalence of intracranial atherosclerotic stroke in Asians. Method We analyzed 352 consecutive patients with ischemic events within the MCA distribution and relevant intracranial arterial stenosis, but no demonstrable carotid or cardiac embolism sources. Conventional angiography was performed in 249 (70.7%) patients, and the remains underwent MRA. The occurrence of the c.14429G>A (p.Arg4810Lys) variant in ring finger protein 213 (RNF213) was analyzed. This gene was recently identified as a susceptibility gene for MMD in East Asians. Results The p.Arg4810Lys variant was observed in half of patients with intracranial stenosis (176 of 352, 50.0%), in no healthy control subjects (n = 51), and in 3.2% of stroke control subjects (4 of 124 patients with other etiologies). The presence of basal collaterals, bilateral involvement on angiography, and absence of diabetes were independently associated with the presence of the RNF213 variant. Among 131 patients who met all three diagnostic criteria and were diagnosed with MMD, three-fourths (75.6%) had this variant. However, a significant proportion of patients who met two criteria (57.7%), one criterion (28.6%), or no criteria (20.0%) also had this variant. Some of them developed typical angiographic findings of MMD on follow-up angiography. Conclusions Careful consideration of MMD is needed when diagnosing ICAS because differential therapeutic strategies are required for these diseases and due to the limitations of the current diagnostic criteria for MMD.

Transcranial motor evoked potential monitoring during the surgical clipping of unruptured intracranial aneurysms

OBJECTIVE The aim of the present study was to evaluate the usefulness of transcranial motor evoked potential (MEP) monitoring and its impact on morbidity after surgical clipping of unruptured intracranial aneurysms. METHODS Motor outcomes were compared before and after the application of MEP monitoring for a one year period. A total intravenous anesthesia was induced and maintained with a continuous infusion of vecuronium. Muscle MEPs were elicited by constant voltage stimulation via subdermal needle electrodes placed at C3 and C4 positions. A more than 50% decrement of MEP amplitudes compared with baseline recordings was regarded as a warning sign and promptly indicated to the surgeon. RESULTS Before the application of MEP monitoring, a new motor deficit was observed in 3 of 66 patients. However, in 98 patients operated under MEP monitoring, no new motor deficit was found except for one patient who manifested delayed hemiparesis 30 h after the operation owing to a cortical vein injury during craniotomy. MEPs deteriorated in 12 patients which were related to hypotension (n=1), temporary clipping (n=7), and permanent clipping (n=4), and recovered in all after prompt corrective measures. After surgical clipping of unruptured aneurysms, the absence of new motor deficits could be reliably anticipated by recovered MEPs as well as unchanged MEPs. CONCLUSIONS Transcranial MEP monitoring is a simple, safe, and reliable tool for the prediction of postoperative motor functions. The ischemic complications can be reduced via prompt corrective measures taken on the basis of MEP changes during aneurysm surgery.

Safety of Early Warfarin Resumption following Burr Hole Drainage for Warfarin-Associated Subacute or Chronic Subdural Hemorrhage

The primary objective of this study was to evaluate the safety of early warfarin resumption following burr hole drainage for warfarin-associated subdural hemorrhage (SDH). This prospective, single-arm, single-center trial was conducted from February 2008 to April 2010. Inclusion criteria were premorbid warfarin therapy, subacute or chronic SDH requiring burr hole drainage, and an International Normalized Ratio (INR) of >1.5 at presentation. Three days after surgery, warfarin was re-administered to reach the target INR range of 1.7-2.5. Patients were followed by regular INR monitoring and serial brain CT scans, which were performed at 1 week, and at 1, 3, and 6 months after surgery. The primary outcome was recurrent SDH incidence. Twenty patients were enrolled and CT scans performed at 1 week revealed no new intracranial hemorrhage in any patient. Subsequent scans were performed at 1 month on 19 patients, and recurrent SDH was observed in three. However, this recurrence rate (15.8%; 95% CI 0,34) did not exceed that of ordinary SDHs, and all recurrent SDHs were successfully managed by repeated burr hole drainage. The other 16 patients completed their 6-month follow-ups uneventfully. SDH recurrence was found to be associated with older age (≥ 75 years), and a thicker SDH (≥ 25 mm), but not with post-operative anticoagulation status. None of the study subjects experienced a thromboembolic event during the study period. Restarting warfarin therapy does not need to be withheld for more than 3 days after burr hole drainage, particularly in patients with a high thromboembolic risk.

The Prediction of Contralateral Progression in Children and Adolescents With Unilateral Moyamoya Disease

Background and Purpose— To evaluate the factors predictive of contralateral progression in children and adolescents with unilateral moyamoya disease (MMD), the authors retrospectively analyzed clinicoradiological findings. Methods— The records of 394 consecutive patients with MMD aged 0 to17 years were reviewed. Unilateral MMD was defined based on the typical angiographic findings of MMD in 1 hemisphere and no abnormality in the contralateral internal carotid artery and the middle cerebral artery. Of the 394 patients with MMD, 45 (11.4%) had unilateral MMD and the prevalence increased with age. Untreated contralateral hemispheres were followed by serial MR angiography. Follow-up angiography was performed if contralateral progression, defined as any noticeable change in the contralateral internal carotid artery and/or middle cerebral artery, was suggested by MR angiography. Results— Eight of the 45 (17.8%) had angiographically documented progression over a mean follow-up of 53.4 months. Mean time to contralateral progression was 27 months (range, 21 to 37 months). An age at diagnosis of <9 years was found to be the only independent predictor of contralateral progression (P=0.025), which persisted despite adjustment for sex and ipsilateral Suzuki stage (hazard ratio, 8.26; 95% CI, 1.01 to 67.94). Other factors, including abnormalities in the contralateral anterior cerebral artery, were not found to be predictive of progression to bilateral MMD. Conclusions— The incidence of contralateral progression in our cohort of children and adolescents with unilateral MMD appears to be lower than those previously reported. Furthermore, contralateral progression tended to occur in children aged <9 years within 3 years of initial diagnosis (32%).

Clinical Course of Asymptomatic Adult Moyamoya Disease

Background: As regular medical check-ups are becoming more common, the prevalence of asymptomatic moyamoya disease (MMD) is increasing. However, the definition and clinical features are still unclear. The lack of precision has hampered the establishment of guidelines for the management of asymptomatic MMD. The purpose of this study was to define and clarify the clinical characteristics of asymptomatic MMD in adults. Methods: We identified all adults (aged ≥18 years) with MMD who underwent digital subtraction angiography or magnetic resonance angiography at our institution from 1995 through 2010. The authors defined asymptomatic MMD as asymptomatic or nonspecific symptom without any infarction or ischemia on magnetic resonance imaging. In our MMD registry, 40 patients (74 hemispheres) were identified and enrolled in this retrospective cohort study. Their demographic, radiological and clinical findings were evaluated. The log-rank test was used to assess prognostic factors. Pearsons correlation test and the Mann-Whitney U test were used to identify correlation angiographic staging and age or perfusion status. Results: Overall, 6 patients underwent indirect bypass surgery and 36 received antiplatelet medication. On initial single positron emission tomography (35 patients, 67 affected hemispheres), basal and acetazolamide stress brain perfusion were decreased in 19 (28.4%) and 22 (32.8%) hemispheres, respectively. Among 70 angiographically evaluated hemispheres, 6 were unilateral MMD; 27 of 64 affected hemispheres (42.2%) had transdural collateral at evaluation. Age (p = 0.309, Pearsons correlation test) and hemodynamic impairment (p = 0.614, Mann-Whitney U test) did not correlate with angiographic staging. During a median 32-month (range 6-203) clinical follow-up, 3 nonsurgically treated patients had a transient ischemic attack, which was associated with decreased vascular reserve (p < 0.001, log-rank test) and smoking (p = 0.017). Other variables did not show a significant association with clinical progression. During a median 24-month (range 12-108) radiological follow-up, 3 patients displayed angiographic progression and 3 displayed new hemodynamic abnormalities. Radiological progressions were related to hypertension only (p = 0.022). In this case series, there was no case of ischemic or hemorrhagic stroke. Conclusion: The findings suggest that asymptomatic MMD in adults is not a stable disease in our definition. However, stroke rate (0%) was lower than previous reports. Lifestyle modification, stroke risk factor control and/or antiplatelet medication seem to be appropriate initial treatments for patients with normal cerebrovascular reserve. A clear definition of asymptomatic MMD and further clarification of its clinical course are needed to set precise treatment guidelines.

A Polymorphism in RNF213 Is a Susceptibility Gene for Intracranial Atherosclerosis

Background Both intracranial atherosclerotic stenosis (ICAS) and moyamoya disease (MMD) are prevalent in Asians. We hypothesized that the Ring Finger protein 213 gene polymorphism (RNF213), a susceptibility locus for MMD in East Asians, is also a susceptibility gene for ICAS in patients whose diagnosis had been confirmed by conventional angiography (absence of basal collaterals) and high-resolution MRI (HR-MRI, presence of plaque). Methods We analyzed 532 consecutive patients with ischemic events in the middle cerebral artery (MCA) distribution and relevant stenotic lesion on the distal internal carotid artery or proximal MCA, but no demonstrable carotid or cardiac embolism sources. Additional angiography was performed on 370 (69.5%) patients and HR-MRI on 283 (53.2%) patients. Results Based on angiographic and HR-MRI findings, 234 patients were diagnosed with ICAS and 288 with MMD. The RNF213 variant was observed in 50 (21.4%) ICAS patients and in 119 (69.1%) MMD patients. The variant was observed in 25.2% of patients with HR-MRI-confirmed ICAS. Similarly, 15.8% of ICAS patients in whom MMD was excluded by angiography had this variant. Among the ICAS patients, RNF213 variant carriers were younger and more likely to have a family history of MMD than non-carriers were. Multivariate testing showed that only the age of ICAS onset was independently associated with the RNF213 variant (odds ratio, 0.97; 95% CI, 0.944–0.99). Conclusions RNF213 is a susceptibility gene not only for MMD but also for ICAS in East Asians. Further studies are needed on RNF213 variants in ICAS patients outside East Asian populations.

Experimental and clinical factors influencing long-term stable in vitro expansion of multipotent neural cells from human adult temporal lobes.

Autologous adult human neural stem cells may be used for regenerative cell therapies bypass potential ethical problems. However, stable in vitro expansion protocols and experimental/clinical factors influencing primary cultures need to be further elucidated for clinically applicable techniques. To address these issues, we obtained biopsy specimens from 23 temporal lobe epilepsy patients and adult human multipotent neural cells (ahMNCs) were primarily cultured in a defined attachment culture condition. When the success of primary cultures was defined as stable expansion of cells (>ten in vitro passages) and expression of NSC markers, success rate of the primary culture was 39% (nine of 23 temporal lobes). During the long-term expansion, expressions of NSC markers and differentiation potentials into astrocytes and neurons were maintained. After the 18th sub-culture, spontaneous senescence and differentiation were observed, and the cultivated ahMNCs ceased their proliferation. The culture results were not affected by seizure characteristics; however, an older age (>40 years) and a smaller sample volume (<2 ml) were found to exert negative influences on the primary culture results. Furthermore therapeutic effects of ahMNCs against stroke were analyzed in an animal model. Transplantation of ahMNCs cells reduced infarction volumes and enhanced motor activity, significantly. The results here would provide promising experimental and clinical strategy of using patient-specific autologous ahMNCs in regenerative medicine in the future.

Neovascularization Precedes Occlusion in Moyamoya Disease: Angiographic Findings in 172 Pediatric Patients

Background: Both basal collaterals (BC) and cortical microvascularization (CM) on angiography have been suggested as moyamoya disease (MMD)-specific findings; however, it is unknown whether the vascular network represents compensatory mechanisms for vascular occlusion or aberrant active neovascularization. Methods: We investigated the grade of antegrade MCA flow, the degree of BC, and the presence of CM on conventional angiography in relation to disease severity in pediatric MMD. CM was defined as enlarged and winding distal cortical arteries and categorized into anterior or posterior CM depending on their sources. Findings from basal and acetazolamide stress brain perfusion SPECT studies were also evaluated. Results: A total of 172 pediatric patients with MMD were enrolled in this study. As the severity of MMD increased, the grade of antegrade MCA flow gradually diminished. While the degree of BC peaked at Suzuki stage 3-4, CM was frequently observed at early MMD stages. About two-thirds of hemispheres with normal antegrade MCA flow on angiography and normal perfusion status on SPECT had anterior and/or posterior CM. Both anterior and posterior CM gradually decreased with the advancement of MMD. Conclusion: Our findings from a large cohort of angiographically confirmed pediatric MMD patients indicate that neovascularization may occur before significant hemodynamic impairment in MMD.

Angiographic analysis of venous drainage and a variant basal vein of Rosenthal in spontaneous idiopathic subarachnoid hemorrhage

The aim of this study was to examine the clinical characteristics and angiographic findings of spontaneous idiopathic subarachnoid hemorrhage (ISAH) and to compare these with those of aneurysmal SAH (ASAH). We retrospectively reviewed the clinical characteristics and venograms of 118 consecutive patients with ISAH during the past 10years for possible abnormalities in venous structures. Also, 57 patients with ASAH during the past 4years were examined. Patients with ISAH showed low frequency of hypertension and no patient suffered from an episode of re-bleeding, or delayed ischemic deficits. Physical actions, including varieties of the Valsalva maneuver, were the causes of ISAH in 17 (29.8%) patients. Compared with patients with ASAH, patients with ISAH showed a significant difference in the drainage patterns of the basal vein of Rosenthal (BVR) (p=0.001). In addition, whereas a linearly decreasing trend toward the primitive type was evident in ASAH, each drainage pattern was distributed evenly in ISAH (linear by linear association, p=0.000). In this study, the primitive drainage pattern of BVR has a relationship with ISAH compared to ASAH. The way in which this venous configuration might influence bleeding remains unknown.