Kyu Won Shim

Management of intracranial cavernous malformation in pediatric patients

ObjectiveCavernous malformations (CMs) are vascular malformations affecting any part of the central nervous system. CMs in the pediatric age group are known to be different from those of adults both in origin and clinical characteristics. In this paper, we report our experience in managing CMs in pediatric patients.Materials and methodsBetween January 1994 and December 2006, 33 patients younger than 20xa0years of age with intracranial CMs were treated with microsurgery or radiosurgery. We retrospectively reviewed the presentation and treatment of these 33 patients (18 boys and 15 girls; average age 11.6xa0years).ResultsThe most common symptom at presentation was seizure (19 children, 57.6%). The most common type of CM, classified on the basis of magnetic resonance imaging, was type II (18, 54.5%). The supratentorial compartment was the most frequent location (27, 71.8%), and only six CMs (18.2%) were observed in the infratentorial compartment. Microsurgery was performed on 25 patients (75.8%), and radiosurgery was performed on eight patients (24.2%). The overall post-treatment results were positive. Only two children (6.1%) had persistent presurgical neurological signs, although the treatment ameliorated them. No progression of the preoperative neurological signs or onset of new neurological deficits was seen in any of the patients. In our patient group, the microsurgical removal of CMs resulted in the prevention of recurrent hemorrhage and the control of seizure disorders in all cases.ConclusionsOur results suggest that pediatric patients with symptomatic CMs should be treated surgically because of the risk of recurrent hemorrhaging and the general benefits of CM removal.

Spinal dysraphism with anorectal malformation: lumbosacral magnetic resonance imaging evaluation of 120 patients

PURPOSEnWe evaluated the prevalence of spinal dysraphism (SD) in patients with anorectal malformation (ARM) by magnetic resonance imaging (MRI).nnnMETHODSnFrom January 2002 to March 2009, 120 patients with ARM who underwent anorectal reconstruction were evaluated for SD with sacral plain film, spinal ultrasonography (US), and lumbosacral MRI. We adopted Krickenbeck international classification of ARM.nnnRESULTSnSpinal dysraphism was present in 41 (34.2%) of 120 patients with ARM, 3 (13.0%) of 23 patients with perineal fistula, 7 (29.2%) of 24 patients with vestibular fistula, 4 (36.4%) of 11 patients with rectovesical fistula, 18 (40.9%) of 44 patients with rectourethral fistula, and 9 (60.0%) of 15 patients with cloacal anomaly (P = .04). Among 41 patients having SD detected by MR, 26 patients (26/41; 63.4%) underwent detethering surgery for tethered spinal cord. The mean sacral ratio (SR) in patients who underwent detethering surgery (0.54 +/- 0.19) was significantly lower than in patients who did not undergo detethering surgery (0.69 +/- 0.13; P < .001). The optimal cutoff for the SR value predicting SD requiring detethering surgery was 0.605, with sensitivity of 65.4% and specificity of 77.7%.nnnCONCLUSIONSnSpinal dysraphism is common in patients with ARM, and its prevalence is higher in patients with complex ARM. Spinal anomalies can occur even with benign types of ARM and, therefore, that all patients should be screened. Magnetic resonance imaging is useful in detecting occult SD that may be missed by conventional radiologic evaluation, physical examination, and spinal US. We further recommend a lumbosacral MRI examination in those whose SR is lower than 0.6.

Treatment modality for intractable epilepsy in hypothalamic hamartomatous lesions

OBJECTIVEHypothalamic hamartomas (HHs) are often associated with early-onset gelastic seizures, thus configuring a well recognized and usually severe case of childhood epilepsy syndrome. We present a treatment modality for intractable epilepsy in hypothalamic hamartomatous lesions. METHODSThis study presents 14 patients with medically refractory seizure associated with HHs treated between 1995 and 2005. The HHs were diagnosed on the basis of magnetic resonance imaging, except in the case of one patient in whom hamartoma was confirmed histologically. There were seven boys and seven girls in this study. The most frequent clinical presentations were seizures. To identify the epileptic focus, we performed comprehensive epilepsy investigations, including electroencephalographic recording using a depth electrode into the hamartoma. RESULTSTo control the seizure, we performed surgical resection in one patient, gamma knife radiosurgery in four patients, and endoscopic disconnection in 11 patients. Seizure outcome was scored according to Engels classification throughout a mean follow-up period of 27.4 months (range, 3–54 mo). Of the 11 patients who underwent endoscopic disconnection, six were seizure-free immediately after surgery. Two patients were already diagnosed as having an HH and underwent gamma knife radiosurgery, but seizure control was not achieved. Their gelastic seizure disappeared after endoscopic disconnection. CONCLUSIONWe confirmed that HHs are intrinsically epileptogenic. Therefore, we suggest that HH-related seizures may be controlled by blocking the seizure propagation from epileptogenic HHs through simple disconnection, regardless of the treatment modality, and the endoscopic disconnection of HHs is safer and more effective than other modalities.

A Multimodal Approach Including Craniospinal Irradiation Improves the Treatment Outcome of High-risk Intracranial Nongerminomatous Germ Cell Tumors

PURPOSEnTo evaluate whether a multimodal approach including craniospinal irradiation (CSI) improves treatment outcome in nongerminomatous germ cell tumor (NGGCT) patients.nnnMETHODS AND MATERIALSnWe reviewed the records of 32 patients with NGGCTs. Fourteen patients belonged to the intermediate prognosis group (immature teratoma, teratoma with malignant transformation, and mixed tumors mainly composed of germinoma or teratoma), and 18xa0patients belonged to the poor prognosis group (other highly malignant tumors). Patients with pure germinoma or mature teratoma were excluded from this study. Nineteen patients were treated with a combination of surgery, chemotherapy, and radiotherapy (RT); 9 patients received chemotherapy plus RT; 3 patients received surgery plus RT; and 1 patient received RT alone. Twenty-seven patientsxa0received CSI with a median of 36 Gy (range, 20-41 Gy) plus focal boost of 18-30.6 Gy, and 5 patients received whole-brain RT (WBRT) (20-36 Gy) or focal RT (50.4-54 Gy). The rate of total and subtotal resection was 71.9%. The median follow-up for surviving patients was 121 months.nnnRESULTSnTreatment failed in 7 patients. Three of the 5 patients who received focal RT or WBRT had local failure. Four cerebrospinal fluid (CSF) failures occurred after CSI. No failure occurred in the intermediate prognosis group. Ten-year recurrence-free survival (RFS) and overall survival (OS) for all patients were 77.6% and 74.6%, respectively. Ten-year RFS for the intermediate and poor prognosis groups were 100% and 61.1%, respectively (p = 0.012). OS for the two groups were 85.1% and 66.7%, respectively (p = 0.215). Tumor histology and CSI were significant prognostic factors for RFS, and CSI was significantly associated with OS.nnnCONCLUSIONSnA multimodal approach was effective for treating NGGCTs. CSI should be considered for patients with poor prognostic histology.

Insular epilepsy surgery under neuronavigation guidance using depth electrode

ObjectivesThe unfavorable surgical results that have been reported with insular epilepsy surgery may be related to inadequate monitoring. Insular epilepsy surgery requires the precise monitoring and tailored removal of the epileptic zone. The purposes of this study were to precisely monitor the hidden cortex and determine the effectiveness of using different monitoring methods, including subpial depth electrodes.Materials and methodsThis is a study of a single center series of six patients (three men, three women) who underwent insular surgery between May 2006 and December 2007. All patients had experienced medically intractable seizures without any evidence of a tumorous condition based on previous examination. We used strip electrode implantation in one patient and stereotactic depth electrode insertion in two patients, which resulted in partial removal of the insular. The other three patients underwent open direct subpial depth electrode insertion, which resulted in total removal of the insular cortex.ResultsThere were no surgery-related complications with the insulectomy after insertion of the subpial depth electrodes, regardless of the monitoring method or extent of removal. All patients except for one showed considerable improvement in epilepsy (83.3% Engle class I, 16.5% Engle class II). In the three patients who had open direct subpial depth electrodes inserted, we achieved total insulectomy without increasing the surgical morbidity, while in the other three patients, the insular removal was only partial.ConclusionWe demonstrate that image-guided insular surgery with safe and accurate depth electrode guidance results in an optimal outcome and complete resection of the insular cortex.

Treatment failure in intracranial primary germinomas.

ObjectA radiation dose of 40–50xa0Gy is able to produce a cure rate of more than 90% in intracranial pure germinoma. However, many attempts have been made to reduce the dose and volume of radiation without compromising the disease control rate because of the toxicity of irradiation. This retrospective study is intended to provide the physician with an appropriate therapeutic strategy.Materials and methodsWe reviewed a series of 10 recurrent germinomas among 117 germinomas diagnosed histologically or clinically between 1979 and 2002. These patients involved underwent three different treatment modalities; radiation alone (Nu2009=u200971), chemotherapy alone (Nu2009=u20099), and combined therapy (Nu2009=u200937). The 10-year overall and relapse-free survival rates were 97 and 93% in the radiation alone group, 89 and 67% in the chemotherapy alone group, and 92 and 92% in the combined therapy group, respectively. As expected, both radiation therapy and combined therapy were effective in controlling the disease. Tumor recurrence was closely related to the volume of radiation but not to the dose of radiation. If the tumor bed and craniospinal axis were fully covered, the radiation dose might be reduced. Chemotherapy alone showed earlier recurrence and a higher tumor recurrence rate. In the case of combined therapy, chemotherapy was useful in reducing the radiation dose but revealed some toxicity (death of two patients).ConclusionsThe investigation of a possible further dose reduction seems worthwhile. Radiation therapy alone with a dose of less than 40xa0Gy should be compared with ongoing chemotherapeutic protocols combined with low-dose irradiation.

Outcomes of epilepsy surgery in childhood-onset epileptic encephalopathy

PURPOSEnto evaluate the outcomes and role of epilepsy surgery in children with intractable epileptic encephalopathy (EE).nnnMETHODSnninety-five children (64 boys, 31 girls) with intractable EE were treated by epilepsy surgery at Severance Childrens Hospital from 2003 to 2008. Surgical treatments included lobar resection, hemispherotomy and corpus callosotomy (CC). Seventy-six children were Lennox-Gastaut syndrome (LGS), and 19 had West syndrome.nnnRESULTSnof the 76 patients with LGS, CC was performed in 37 patients (48.7%), lobar resection in 29 (38.2%) and hemispherotomy in 10 (13.2%). Of the 19 patients with West syndrome, respective surgery was performed in 15 patients (78.9%) and CC in 4 (21.1%). Of the patients receiving respective surgery, Engels class I outcomes were achieved for 24 of 39 (61.5%) of LGS patients, and for 9 of 15 (60.0%) of West syndrome. Malformations of cortical development were commonly observed, appearing in 73.5% (36/49). In neuropsychiatric tests, 19 of 27 with LGS demonstrated improvement in postoperative cognitive function. More significant intellectual improvement correlated well with shorter epilepsy duration, good seizure outcomes, and decreased number of antiepileptic drugs.nnnCONCLUSIONSnepilepsy surgery should be considered in treating childhood intractable EE with expectation of improvement of both seizure and cognitive outcomes, even in cases of LGS.

Isolation of mesenchymal stem-like cells in meningioma specimens.

Cells resembling bone marrow mesenchymal stem cells (BM-MSCs) have been isolated from glioma specimens; however, little is known about the existence of mesenchymal stem-like cells (MSLCs) in meningioma. Here, we hypothesized that cells similar to BM-MSCs exist in meningioma specimens and sought to investigate whether these putative meningioma stroma MSLCs (MS-MSLCs) could be isolated. To this end, we cultured fresh meningioma specimens using the same protocols as used previously to isolate BM-MSC. Cultured cells were analyzed for surface markers associated with BM-MSCs by fluorescence-activated cell sorting (FACS) and candidate cells were exposed to mesenchymal differentiation conditions. Possible locations of MS-MSLCs were determined by immunohistochemical analysis of sections of meningioma specimens. Spindle-shaped and, adherent cells similar to BM-MSCs were isolated in 2 of 20 meningioma specimens. FACS analysis showed that the surface markers of MS-MSLCs were similar to those of BM-MSCs and the chosen cells demonstrated an ability to differentiate into osteogenic, adipogenic and chondrogenic cells. The tumorigenicity of MS-MSLCs was tested by injection of these cells into the brain of athymic nude mice; no tumors were subsequently discovered. Immunohistochemical analyses indicated that CD105+ cells were closely associated with endothelial cells and pericytes in meningioma specimens. Our results established for the first time that cells similar to BM-MSCs exist in meningioma specimens. These cells, termed MS-MSLCs, could be one component of the meningioma cellular microenvironment.

Sacral Reconstruction with a 3D-Printed Implant after Hemisacrectomy in a Patient with Sacral Osteosarcoma: 1-Year Follow-Up Result

Pelvic reconstruction after sacral resection is challenging in terms of anatomical complexity, excessive loadbearing, and wide defects. Nevertheless, the technological development of 3D-printed implants enables us to overcome these difficulties. Here, we present a case of sacral osteosarcoma surgically treated with hemisacrectomy and sacral reconstruction using a 3D-printed implant. The implant was printed as a customized titanium prosthesis from a 3D real-sized reconstruction of a patients CT images. It consisted mostly of a porous mesh and incorporated a dense strut. After 3-months of neoadjuvant chemotherapy, the patient underwent hemisacretomy with preservation of contralateral sacral nerves. The implant was anatomically installed on the defect and fixed with a screw-rod system up to the level of L3. Postoperative pain was significantly low and the patient recovered sufficiently to walk as early as 2 weeks postoperatively. The patient showed left-side foot drop only, without loss of sphincter function. In 1-year follow-up CT, excellent bony fusion was noticed. To our knowledge, this is the first report of a case of hemisacral reconstruction using a custom-made 3D-printed implant. We believe that this technique can be applied to spinal reconstructions after a partial or complete spondylectomy in a wide variety of spinal diseases.

Treatment strategy for intracranial primary pure germinoma

ObjectThis 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 methodsBetween 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 16.2xa0years (range 6–31xa0years). There were 19 men and 9 women (men/women ratiou2009=u20092.1:1). 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 58xa0months (mean 58.2xa0months, range 41–82xa0months), and for combine therapy group, the median was 68.5xa0months (mean 67.8xa0months, range 41–88xa0months). 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.ConclusionNeo-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.