Neuroendoscopy: Current and Future Perspectives.

Neuroendoscopic surgery is performed because it causes minimal damage to normal structures, carries a lower rate of complications, and achieves excellent outcomes. Surgeons using an endoscope and related instruments can perform complex operations through very small incisions, which is especially useful for minimally invasive procedures for the brain and spine. Neuroendoscopic surgery is now performed in cases of obstructive hydrocephalus, various intraventricular lesions, hypothalamic hamartomas, craniosynostosis, skull base tumors, and spinal lesions. This review discusses the brief history of neuroendoscopy and the current state and future perspectives of endoscopic surgery.

The roles of methylenetetrahydrofolate reductase 677C>T and 1298A>C polymorphisms in moyamoya disease patients.

PURPOSE: The methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C polymorphisms, which are associated with hyperhomocysteinemia and nitric oxide (NO) deficiency (which is related to atherothrombosis and cerebral ischemia), have not been studied in moyamoya disease. A case-control study was performed to investigate whether the MTHFR 677C>T and 1298A>C polymorphisms contribute to moyamoya disease (MMD). METHODS: One hundred and seven Korean patients with MMD (mean age, 20.85 ± 15.89 years; 66.4 % female) and 232 healthy control subjects (mean age, 23.99 ± 16.16 years; 56.8 % female) were included. Genotyping for the MTHFR 677C>T and 1298A>C polymorphisms and measurements of homocysteine, folate, vitamin B12, and NO in the cerebrospinal fluid (CSF) were performed. The statistical analysis was performed by multivariate linear regression and logistic regression. RESULT: The MTHFR 677CT+TT genotype frequency was significantly increased with early-onset MMD (<10 years) compared with late-onset MMD (≥10 years) (adjusted odds ratio, 3.392; 95 % confidence interval, 1.294-8.893, P = 0.013). The MTHFR 677C-1298C/677T-1298A diplotype (1.71 ± 1.23 arbitrary units) presented significantly lower NO levels in the CSF compared with the 677C-1298A/677C-1298A diplotype (11.40 ± 12.24 arbitrary units). CONCLUSION: The MTHFR 677C>T and 1298A>C polymorphisms have restricted roles in the Korean MMD population. Therefore, further studies involving larger and more heterogeneous cohorts are needed to extend our understanding of the influence of polymorphisms in MTHFR and other thrombophilic genes on MMD.

Treatment strategy for intracranial primary pure germinoma.

OBJECT: This prospective randomized clinical study will address the efficacy of radiation (RT)-alone and combined with pre-RT chemotherapy (CTX) treatments and propose the novel standard treatment strategy for intracranial primary pure germinoma. MATERIALS AND METHODS: Between 2005 and 2008, there were 54 patients diagnosed with intracranial primary pure germinomas in a single institute. Twenty-eight patients were enrolled. The mean age of the patients was 16.2 years (range 6-31 years). There were 19 men and 9 women (men/women ratio = 2.1:1). There were 21 patients with solitary tumors and 7 with multiple tumors. These patients were randomized as RT-only treatment group (11 solitary and 3 multiple tumors) and combined (10 solitary and 4 multiple tumors, neo-adjuvant CTX followed by response-adapted RT) treatment group. The follow-up period for RT only group has a median of 58 months (mean 58.2 months, range 41-82 months), and for combine therapy group, the median was 68.5 months (mean 67.8 months, range 41-88 months). All 14 patients in the RT-only group showed complete response (CR) and no recurrence. Eleven patients in the combined group had CR and three patients had partial response after neo-adjuvant CTX. All patients responded to RT as CR without recurrence. At the time of analysis, all 28 patients were alive without evidence of disease. CONCLUSION: Neo-adjuvant CTX for localized germinomas seems to be unnecessary as a method to reduce radiation dose in our RT protocol. However, the effective control of multifocal or disseminated germinoma can be achieved by neo-adjuvant CTX followed by response-adapted reduced dose RT.

Treatment modalities for intractable epilepsy in hypothalamic hamartoma.

Hypothalamic hamartoma (HH) is usually associated with refractory epilepsy, cognitive impairment, and behavioral disturbance. There is now increasing evidence that HH can be treated effectively with a variety of neurosurgical approaches. Treatment options for intractable gelastic seizure in HH patients include direct open surgery with craniotomy, endoscopic surgery, radiosurgery with gamma knife (GKS) and stereotactic radiofrequency thermocoagulation. Selection of treatment modalities depends on type and size of the HH and the surgeon's preference. Two surgical techniques, resection and disconnection, had been described with favorable outcomes. Pretreatment evaluation, patient selection, surgical techniques, complications, and possible selection of treatment are discussed in this chapter.

The role of VEGF and KDR polymorphisms in moyamoya disease and collateral revascularization.

We conducted a case-control study to investigate whether vascular endothelial growth factor (VEGF -2578, -1154, -634, and 936) and kinase insert domain containing receptor (KDR -604, 1192, and 1719) polymorphisms are associated with moyamoya disease. Korean patients with moyamoya disease (n = 107, mean age, 20.9±15.9 years; 66.4% female) and 243 healthy control subjects (mean age, 23.0±16.1 years; 56.8% female) were included. The subjects were divided into pediatric and adult groups. Among the 64 surgical patients, we evaluated collateral vessel formation after 2 years and divided patients into good (collateral grade A) or poor (collateral grade B and C) groups. The frequencies and distributions of four VEGF (-2578, -1154, -634, and 936) and KDR (-604, 1192, and 1719) polymorphisms were assessed from patients with moyamoya disease and compared to the control group. No differences were observed in VEGF -2578, -1154, -634, and 936 or KDR -604, 1192, and 1719 polymorphisms between the control group and moyamoya disease group. However, we found the -634CC genotype occurred less frequently in the pediatric moyamoya group (p = 0.040) whereas the KDR -604C/1192A/1719T haplotype increased the risk of pediatric moyamoya (p = 0.024). Patients with the CC genotype of VEGF -634 had better collateral vessel formation after surgery. Our results suggest that the VEGF -634G allele is associated with pediatric moyamoya disease and poor collateral vessel formation.

Association of the miR-146aC>G, miR-196a2C>T, and miR-499A>G polymorphisms with moyamoya disease in the Korean population.

Recent evidence has demonstrated associations between the single nucleotide polymorphism (SNP) rs11614913 in miR-196a2C>T and various pathologies. A main target of miRNA-196a is annexin A1 (lipocortin1, ANXA1), which is associated with increased multiple malignant tumors in brain models of ischemia and reperfusion injury. To determine the effects of miRNA SNPs in moyamoya disease, we recruited 107 patients with moyamoya disease and 240 healthy controls from a Korean study population and determined the genotype of each participant from whole blood samples. We compared the patient and the control genotypes and allele frequencies of rs2910164, rs11614913, and rs3746444 and investigated the association of the three SNPs with age and clinical characteristics, such as cerebral hemorrhage or infarction. rs11614913 in miR-196a2C>T was significantly associated with moyamoya disease. The association of this SNP with adult age and cerebral infarction was statistically significant compared to the control group, but the association with hemorrhagic moyamoya disease was not significant. The CT+CC genotype of miR-196a2 was represented at an increased frequency among patients with moyamoya disease. However, the distribution of miR-146aC>G and miR-499A>G genotypes was not statistically different between participants who were healthy and those with moyamoya disease. Thus, the SNP rs11614913 is significantly associated with moyamoya disease, as well as cerebral infarction and adult age in patients with moyamoya disease. This study demonstrates a higher frequency of the CT+CC genotype of the SNP rs11614913 in miR-196a2C>T, which suggests that miR-196a2 may play a role in the pathogenesis of moyamoya disease.

The clinical features and surgical outcomes of pediatric patients with primary spinal cord tumor.

BACKGROUND: Primary spinal cord tumors (PSCTs) in pediatric patients are rare, with a reported overall incidence rate of 1-2.6 per one million children. We reviewed our experience of surgically treated 27 pediatric patients with PSCT and discussed the clinical features, radiological findings, surgical outcomes, and prognostic factors. METHODS: Between March 1999 and March 2010, a total of 27 pediatric patients with PSCT were surgically treated in a single institution. We retrospectively analyzed their data. RESULTS: There were 13 females and 14 males, and their ages ranged from 6 months to 19 years (mean age, 12.1 years). The most common presenting symptom was motor weakness, and the histologic type of the tumors were mainly schwannoma, astrocytoma, and ependymoma. The tumor was completely resected in 17 patients, subtotally resected in 7 patients, and partial resection or biopsy was performed in 3 patients. Adjuvant chemotherapy was performed in 9 patients, and radiotherapy in 12 patients, respectively. The average follow-up period was 33.5 months (1.17-129). Five patients experienced the progression of disease, and three of them expired. The mean time for disease progression was 19.0 months (4.5-48.7). CONCLUSIONS: PSCT in pediatric patients can be surgically removed with an acceptable low surgical morbidity. Progression-free survival was found to be related to the grade of tumor and the extent of tumor resection. Early diagnosis and treatment anticipate good functional neurologic outcome.

Moyamoya syndrome after radiation therapy: case reports.

UNLABELLED: Potentially harmful effects of irradiation on the developing central nervous system have been well documented. We report 2 pediatric patients with moyamoya syndrome developed after irradiation. CASE: A 3-year-old girl had received 4,860 cGy of postoperative radiation for optic pathway glioma. Cerebral angiography 7 months after completion of the radiation therapy revealed progressive cerebral arterial occlusive disease, involving the internal carotid artery on either side of the circle of Willis, with abnormal netlike vessels. Another 5-year-old girl had received 3,600 cGy of postoperative radiation on the cerebrum for a medulloblastoma. Two years later, she was diagnosed with moyamoya syndrome and treated with indirect revascularization. She died due to further progressive obstruction of the right M1 and A1 on the unoperated hemisphere, in spite of well-developed collateral circulation from the superficial temporal artery and middle meningeal artery on the operated left hemisphere. We suggest that radiation therapy with portals typically including carotid siphon may particularly cause vascular damage, regardless of the tumor pathology and lead to radiation-induced moyamoya syndrome. The prognosis may be poorer in case of poor collateral flow and rapid progression. The radiation therapy may cause fatal vascular damage so it should be taken into consideration when a treatment plan is being formulated for young patients.

The relationships between endothelial nitric oxide synthase polymorphisms and the formation of intracranial aneurysms in the Korean population.

OBJECT: Some genetic factors are known to be associated with the formation of cerebral aneurysms in the Caucasian population. One of these factors is endothelial nitric oxide synthase (eNOS) gene polymorphisms. Endothelial nitric oxide synthase genes encode eNOS, which synthesizes NO from l-arginine. There continues to be controversy about the relationships between eNOS gene polymorphisms and the formation of intracranial aneurysms. In this study, the authors evaluated these relationships in the Korean population. METHODS: Three eNOS polymorphisms (eNOS 27VNTR, T786C, and G894T) were genotyped in 96 patients with ruptured aneurysms, 53 patients with unruptured aneurysms, and in 121 volunteers via polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The mean ages of the patients and healthy volunteers were 52.9 ± 12.3 years and 55.2 ± 9.1 years, respectively. The patient group was composed of 56 men and 93 women, and the healthy volunteer group was composed of 46 men and 75 women. Only the incidence of smoking history was significantly higher in the patient group than in the control group (p = 0.001). The genotypic frequencies for the 3 eNOS gene polymorphisms were in agreement with those predicted by Hardy-Weinberg equilibrium. There were no significant associations between the eNOS recessive models and the formation of an aneurysm. The authors found no genotypic differences between similar races among patients with aneurysms. CONCLUSIONS: The present study shows that eNOS 27VNTR, T786C, and G894T polymorphisms cannot be used as indicators of the formation of intracranial aneurysms in Korean patients. To confirm these findings an additional analyses might need to be performed using a larger sample size. There were no differences in the genotypic distributions and allelic frequencies between similar races among patients with aneurysms, which were the same in previously reported normal populations.

Age-specific eNOS polymorphisms in moyamoya disease.

OBJECTIVE: We conducted a case-control study to investigate whether polymorphisms in eNOS are related to the age-specific onset of moyamoya disease. MATERIALS AND METHODS: Ninety-three Korean patients [mean age, 23.0 ± 16.1 years; 59 female (63.4%) and 34 male (36.6%)] with moyamoya disease were consecutively recruited for this study. Three hundred twenty-eight healthy subjects [mean age, 27.7 ± 16.2 years; 217 female (66.2%), 111 male (33.8%)] were consecutively included in the control group. The subjects were divided into pediatric (< 20 years) and adult (≥ 20 years) groups. We further divided the moyamoya group into ischemic and hemorrhagic groups based on clinical and MRI findings. The frequencies and distributions of four eNOS polymorphisms (eNOS -922A>G, -786T>C, 4a4b, and 894G>T) were assessed in pediatric and adult patients with moyamoya disease and compared to the frequencies and distribution in the control group. RESULTS: No differences in eNOS polymorphisms were observed between control and moyamoya disease group. However, we found that the 4a4b sequences was less frequent in the adult group (p = 0.029). Compared to the control group, there were differences in the haplotype distribution of the study group, specifically the A-4b-G haplotype, which was seen more frequently in the adult patient group. CONCLUSION: Our results suggest that pediatric and adult-onset moyamoya disease have different genetic backgrounds. These genetic differences can affect age-specific clinical characteristics, such as cerebral ischemia and hemorrhage.

Natural history and progression factors of unilateral moyamoya disease in pediatric patients.

PURPOSE: Thirty-four pediatric age patients with unilateral moyamoya disease (MMD) were reviewed to analyze the natural history and the predictive factors for progression to bilateral MMD. METHODS: Forty out of 259 MMD patients cared for between January 2000 and June 2008 in the Severance Hospital had unilateral lesion. These patients were followed for a mean of 32.3 months for their symptoms and imaging studies. Thirty-four out of 40 patients were included in this study. Magnetic resonance angiography (MRA) and magnetic resonance perfusion (MR perfusion) images were taken for all patients for initial diagnosis and repeated at 6 months from the initial diagnosis and then at yearly basis. Clinical manifestations, the results of imaging studies, outcome of the indirect revascularization procedure, and the progression of the lesion were reviewed in this study. RESULTS: Of these 34 patients, contralateral progression was identified in 20 patients (58.8%). Fourteen (70%) out of the 20 patients presented with anterior cerebral artery abnormalities at diagnosis progressed to bilateral disease as well as did 5 (83%) out of 6 patients with middle cerebral artery lesions at the initial examination. Among the 34 patients, six exhibited familial history of MMD and all of them progressed to bilateral disease (100%, p < 0.005). CONCLUSION: Careful and long-term follow-up would be essential to evaluate the hemodynamic status and progression to bilateral disease in unilateral MMD patients to make prompt decision for a surgical revascularization.

Reduced-dose craniospinal radiotherapy followed by high-dose chemotherapy and autologous stem cell rescue for children with newly diagnosed high-risk medulloblastoma or supratentorial primitive neuroectodermal tumor.

BACKGROUND: In this study, we investigated the effects of reduced-dose craniospinal radiotherapy (CSRT) followed by tandem high-dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) in children with a newly diagnosed high-risk medulloblastoma (MB) or supratentorial primitive neuroectodermal tumor (sPNET). METHODS: Between March 2005 and April 2007, patients older than 3 years with a newly diagnosed high-risk MB or sPNET were enrolled. The patients received two cycles of pre-RT chemotherapy consisting of cisplatin, etoposide, vincristine, and cyclophosphamide (cycle A), and carboplatin, etoposide, vincristine, and ifosphamide (cycle B), followed by CSRT with 23.4 Gy and local RT with 30.6 Gy. After four cycles of post-RT chemotherapy (cycles A, B, A, and B), tandem double HDCT with ASCR was performed. RESULTS: A total of 13 patients (MB=11, sPNET=2) were enrolled. Of these, one patient progressed, one patient died of septic shock after the second cycle of B, and one patient relapsed after the third cycle of B. The 3-year event-free survival (EFS) rate of the patients intended for HDCT was 76.9%, whereas the 3-year EFS rate of the patients who received HDCT was 100%. No treatment-related mortality occurred during HDCT. CONCLUSION: Although the follow-up period was short and the patient cohort was small in size, the results of this study are encouraging. The limited toxicity and favorable EFS rate observed in children treated with reduced-dose CSRT followed by HDCT and ASCR warrant further exploration in a larger study population.

Are arachnoid cysts localized hydrocephali?

We report 2 cases of arachnoid cysts related to a head trauma. The first case involved a 1-year-old girl who developed an arachnoid cyst 7 months after suffering a head trauma due to a motor vehicle accident, and the second case involved a 1-year-old boy whose arachnoid cyst was first noted 2 months subsequent to his premature birth. We present the serial imaging for both cases. Choi and Kim [Pediatr Neurosurg 1998;29:260-266] postulated that head trauma in infancy may contribute to the pathogenesis of arachnoid cysts in some cases. In presenting our cases, we support this hypothesis, and further postulate that the arachnoid cysts may in fact be localized hydrocephali, triggered either by head trauma or by prematurity.

What should we do with a discontinued shunt?

PURPOSE: The reported rate is up to 10% of shunt disconnection or fracture, either ventriculoperitoneal or subduroperitoneal. However, not all of shunt discontinuity is associated with shunt malfunction. We analyzed the discontinuity of the shunt system and related factors and tried to present a follow-up policy. METHODS: This is a retrospective study involving 22 patients who presented with shunt disconnection because of malfunction or other reasons between January 2003 and October 2008. To evaluate shunt function, we performed a shuntogram, temporary ligation, or intraoperative exploration. RESULTS: Nine (40.9%) of 22 patients had nonfunctioning shunts. The shunt system was removed in eight cases, and one patient refused surgical management. Of these 22 patients with disconnected shunts, 17 shunts placed in the occipital area were discontinued. The discontinuations were mostly fractured at neck (52%), not disconnected at connection site. CONCLUSION: Shunt disconnection has not been always represented a shunt malfunction. We thought many patients with disconnected shunt may be independent from shunt system, and it can be a good chance for patient to remove the shunt system.

Intraventricular hemorrhage long after successful encephaloduroarterio synangiosis in moyamoya patient.

Intraventricular hemorrhage long after successful encephaloduroarterio synangiosis (EDAS) is very rare. The effect of revascularization surgery for preventing hemorrhagic event of moyamoya disease remains controversial. We report a 17-year-old female with intracerebral hemorrhage and intraventricular hemorrahge 10 years after successful EDAS. Even though cerebral vessels angiography showed good collateral circulations without specific weak points, a cerebral hemorrhage could occur in patient with ischemic type of moyamoya disease long after successful indirect bypass operations. Good collateralization of cerebral angiography or magnetic resonance perfusion image after indirect bypass surgery would ensure against ischemic symptoms, not a hemorrhage. And, thus a life-time follow-up strategy might be necessary even if a good collateral circulation has been established.

Treatment and outcomes of primary intracranial teratoma.

PURPOSE: Until recently, postoperative adjuvant treatment for intracranial teratomas has remained controversial because of the rarity of the tumors and the heterogeneity of histologic types. To define optimal therapy modalities, we retrospectively analyzed the treatment of patients with intracranial teratomas. METHODS: Between 1979 and 2007, 31 patients with intracranial teratomas were treated at our institution. The median age of the 31 patients was 14.8 years. The median follow-up time was 72.7 months (range 11 approximately 291 months). Perioperative radiochemotherapy was done in 19 patients. Proper chemotherapy regimens were followed, such as PE (cisplatin and VP-16), PVB (cisplatin, VP-16, and bleomycin), ICE (carboplatin, VP-16, and ifosfamide), and NGGCT (etoposide, carboplatin, bleomycin, and cyclophosphamide with mesna). RESULTS: Eight patients experienced recurrence, and a second operation was carried out in six patients. Fifteen patients survived for more than 5 years without recurrence, irrespective of having received adjuvant therapies. The 5-year survival rate of the 31 patients was 74%. CONCLUSION: Treatment of intracranial teratomas is very difficult because of the heterogeneity of the tumor cells from totipotent origins. Accurate histological diagnosis of teratoma subtypes is the most important factor for adequate treatment, and proper therapeutic protocols are needed to cure teratomas.

Treatment option for arachnoid cysts.

OBJECTIVE: The objective of this study is to establish which treatment is the best operative intervention for arachnoid cyst. MATERIALS AND METHODS: We reviewed a series of 209 cases with arachnoid cysts focusing on the effectiveness and safety. The cysts were treated with several surgical procedures including open surgery for fenestration, endoscopic fenestration, or cystoperitoneal shunting. RESULTS: Follow-up imaging studies showed that 176 out of 209 arachnoid cysts (84.2%) reduced in size during a mean postoperative follow-up period of 6.9 years (range, 1 to 14 years). Although a cystoperitoneal shunt was the best method for early achieving an obliteration of the sylvian cyst (89%), it had the danger of shunt dependency (42%) in addition to four early complications. Although endoscopic fenestration tended to be less effective in reducing the size of a sylvian cyst, it was safe and particularly effective in completely obliterating a suprasellar, quadrigeminal, and prepontine cyst. CONCLUSION: Although the shunt for arachnoid cyst can get the more rapid good radiological outcome, the shunt-related complication and dependency would be hazardous. We suggest that endoscopic or reduced open procedures offer the advantage of avoiding a large craniotomy or the known complications of a cystoperitoneal shunt in treatment of arachnoid cysts. We could get the nearly same surgical outcome without shunt complications with endoscopic or open procedures.

The history of ependymoma management.

INTRODUCTION: The ependymomas are relatively not a common tumor. However, most clinicians agree that the radical removal of the tumor is the most important prognostic factor. MORBIDITY OF TREATMENT: Tumor removal was not sufficient before the era of magnetic resonance imaging (MRI) and resulted in a considerable operative morbidity and mortality. As the microneurosurgical techniques and microsurgical anatomy become popular and the MRI provide more detailed anatomical information preoperatively, radical removal of this complex and complicated tumor can be more feasible. In childhood ependymoma, the treatment-related morbidity and mortality can be the special issues, which can modify the policy of management safe tumor removal and minimal adjuvant treatment, which are extremely important. RADIATION THERAPY: Radiation treatment has been the option for disseminated disease and residual tumor. With the advancement of detailed MR anatomical information, safer and more delicate radiation becomes possible with newer radiation modalities, three-dimensional conformal radiotherapy, intensity modulating radiotherapy, and tomotherapy. PROGNOSTIC FACTORS: Although many clinicians believe that the ependymomas are inheritably chemoresistant, the new targets for the treatment are under investigation or clinically tried. Also, the genetic alterations of ependymoma are developing and might be a promising target. CONCLUSION: The surgical techniques and assistant modalities for tumor removal are still advancing. So, the outcome of ependymoma is still improving. Unfortunately, newer treatment modalities, such as new chemotherapeutic agent and gene modification agent, are still not promising. The history of ependymoma management is still in progress.

Low-dose craniospinal irradiation as a definitive treatment for intracranial germinoma.

PURPOSE: To determine the optimal radiotherapy (RT) dose and volume for treatment of intracranial germinoma. MATERIALS AND METHODS: Eighty-one intracranial germinoma patients (33 pathologically-verified; 48 presumed by radiosensitivity testing) treated with RT alone between 1971 and 2002 were analyzed. The RT volume varied from focal (13) to whole brain (8), or to the entire neuraxis (60). All the cases after 1982 received craniospinal irradiation (CSI). Radiation dose was reduced gradually during the study period from 59 to 39.3 Gy for primary tumors, and from 34.2 to 19.5 Gy for the neuraxis. The median follow-up time was 120 months (48-260 months). RESULTS: Five- and ten-year relapse-free survival rates were 98.8% and 94.1%, respectively. All the recurrences occurred in the patients who received local (4/13) or whole brain RT (1/8). None of the patients who received CSI suffered from a recurrence. Forty-six patients received 45 Gy or less to the primary site and 22 patients received less than 20 Gy to the spinal axis. CONCLUSION: Low-dose CSI-based RT should remain the standard treatment for intracranial germinoma. The RT dose can be reduced to 39.3 Gy for primary tumor sites and to 19.5 Gy for the spinal axis.