Spectrum of neurosurgeon's role in epilepsy surgery.

It is well known that there is high quality evidence of epilepsy surgery as an effective and safe option for patients with drug refractory epilepsy by advanced imaging technology and computerized electrophysiological facilities during recent three decades. However, it still remains debate regarding necessities of epilepsy surgery in terms of less satisfactory surgical outcome, especially in non-lesional neocortical epilepsies. This review is for the role of epileptic neurosurgeon rather than the role of epilepsy surgery, namely, the necessity of neurosurgeon's positive participation starting from the first visit of epilepsy patients followed by pertaining process by stages and its degree of contribution. All experienced epilepsy centers also need innovative or challenging trial absolutely through this kind of standpoint, because all of the present protocols and techniques are coming from the past. In any event, the interdepartmental and interpersonal cooperation is inevitable especially for improving patient's quality of life. Serious neurosurgical considerations are needed for patients with intractable epilepsies, especially in referred cases from other center for the purpose of double check, and incongruent cases with contrary opinions by epileptologist.

Emerging surgical strategies of intractable frontal lobe epilepsy with cortical dysplasia in terms of extent of resection.

OBJECTIVE: Cortical dysplasia (CD) is one of the common causes of epilepsy surgery. However, surgical outcome still remains poor, especially with frontal lobe epilepsy (FLE), despite the advancement of neuroimaging techniques and expansion of surgical indications. The aim of this study was to focus on surgical strategies in terms of extent of resection to improve surgical outcome in the cases of FLE with CD. METHODS: A total of 11 patients of FLE were selected among 67 patients who were proven pathologically as CD, out of a total of 726 epilepsy surgery series since 1992. This study categorized surgical groups into three according to the extent of resection : 1) focal corticectomy, 2) regional corticectomy, and 3) partial functional lobectomy, based on the preoperative evaluation, in particular, ictal scalp EEG onset and/or intracranial recordings, and the lesions in high-resolution MRI. Surgical outcome was assessed following Engel's classification system. RESULTS: Focal corticectomy was performed in 5 patients and regional corticectomy in another set of 5 patients. Only 1 patient underwent partial functional lobectomy. Types I and II CD were detected with the same frequency (45.45% each) and postoperative outcome was fully satisfactory (91%). CONCLUSION: The strategy of epilepsy surgery is to focus on the different characteristics of each individual, considering the extent of real resection, which is based on the focal ictal onset consistent with neuroimaging, especially in the practical point of view of neurosurgery.

Aberrant CpG islands hypermethylation profiles in malignant gliomas.

BACKGROUND: The authors analyzed whether the promoter hypermethylation of cancer-related genes was involved in the tumorigenesis of malignant gliomas. METHODS: A total of 29 patients received surgery and histologically confirmed to have malignant gliomas from January 2000 to December 2006. The promoter methylation status of several genes, which were reported to be frequently methylated in malignant gliomas, was investigated using methylation-specific polymerase chain reaction. RESULTS: All cases of malignant gliomas represented the promoter hypermethylation in at least 2 or more genes tested. Of 29 tumors, 28 (96.55%) showed concurrent hypermethylation of 3 or more genes. Ras association domain family member 1, epithelial cadherin, O-6 methyl guanine DNA methyltransferase, thrombospondin 1, p14 and adenomatous polyposis coli were frequently methylated in high grade gliomas including glioblastomas, anaplastic astrocytomas, and anaplastic oligodendrogliomas. CONCLUSION: Aberrant hypermethylation profile was closely related with malignant gliomas suggesting that epigenetic change may play a role in the development of malignant gliomas. Two or three target genes may provide useful clues to the development of the useful prognostic as well as diagnostic assays for malignant gliomas.

Helenalin-induced apoptosis is dependent on production of reactive oxygen species and independent of induction of endoplasmic reticulum stress in renal cell carcinoma.

Helenalin, a sesquiterpene lactone, exhibits anti-inflammatory and anti-tumor activities. Here, we investigated whether helenalin could induce apoptosis in human renal carcinoma Caki cells. Helenalin increased apoptosis in dose dependent manner in Caki cells, and also induced apoptosis in other carcinoma cells, such as human renal carcinoma ACHN cells, human colon carcinoma HT29 and HCT116 cells. We found that helenalin markedly induced endoplasmic reticulum (ER) stress-related genes, such as regulated in development and DNA damage responses (REDD) 1, activating transcription factor-4 (ATF4) and/or the CCAAT enhancer-binding protein-homologous protein (CHOP). However, down-regulation of ATF4 and/or CHOP expression by siRNA had no effect on helenalin-induced apoptosis in Caki and HCT116 cells. Helenalin increased production of intracellular reactive oxygen species (ROS). Furthermore, ROS scavengers, N-acetylcystine (NAC), and glutathione ethyl ester (GEE), reduced helenalin-induced apoptosis. Taken together, helenalin induced apoptosis via ROS generation in human renal carcinoma Caki cells.

Comparison between Initial and Recent Surgical Outcome of 15-Year Series of Surgically Remediable Epilepsy.

OBJECTIVE: The aim of this study is to compare the surgical outcome of the initial and recent surgical cases, during our 15-years experience, in terms of the surgical strategies and the prognostic factors for surgically remediable epilepsy. METHODS: We retrospectively reviewed and compared the surgical outcomes between the initial 256 (Group I) and recent 139 (Group II) patients according to the time period of operation for a total of 518 consecutive epilepsy surgeries at our institution since 1992. The patients of the middle intermediate period, which were subjected to changed surgical strategies, were excluded. RESULTS: The surgical outcome data from the initial and recent groups showed a much improved outcome for patients who underwent temporal lobe epilepsy (TLE) surgery over time. The number of patients with a good outcome (Engel class I-II) was much increased from 87.7% (178 TLE cases of Group I) to 94.8% (79 TLE cases of Group II) and this was statistically significant (p = 0.0324) on univariate analysis. Other remarkable changes were the decreased performance of intracranial invasive studies from 43.5% in Group I to 30.9% in Group II due to the advanced neuroimaging tools. The strip/grid ratio was reduced from 131/32 in Group I to 17/25 in Group II, because of a markedly reduced mesial TLE surgery and an increased extratemporal epilepsy surgery. CONCLUSION: Our results show that surgical outcome of epilepsy surgery has improved over time and it has shown to be efficient to control medically intractable epilepsy. Appropriate patient selection, comprehensive preoperative assessments and more extensive resection are associated with good postoperative outcomes.

Cerebellar ganglioglioma.

The location of ganglioglioma (GG) within the infratentorial compartment is unusual. The authors report a rare case of GG in the cerebellar hemisphere. A 12-year-old boy suffered from headache and gait disturbance. Neuroimaging studies demonstrated a large enhancing cerebellar mass with cystic components compressing the forth ventricle. After complete resection of the tumor, the patient became symptom free. Histological examination on the tumor disclosed glial cells and dysplastic ganglion cells. Although it is a rare tumor, in the appropriate clinical setting, a GG should be considered in the presence of a cerebellar mass with both solid and cystic components on magnetic resonance images in children.

Expression of cancer-testis genes in brain tumors.

OBJECTIVE: Cancer-testis (CT) genes are considered promising candidates for immunotherapeutic approaches. The aim of this study was to investigate which CT genes should be targeted in immunotherapy for brain tumors. METHODS: We investigated the expression of 6 CT genes (MAGE-E1, SOX-6, SCP-1, SSX-2, SSX-4, and HOM-TES-85) using reverse-transcription polymerase chain reaction in 26 meningiomas and 32 other various brain tumor specimens, obtained from the patients during tumor surgery from 2000 to 2005. RESULTS: The most frequently expressed CT genes of meningiomas were MAGE-E1, which were found in 22/26 (85%) meningioma samples, followed by SOX-6 (9/26 or 35%). Glioblastomas were most frequently expressed SOX-6 (6/7 or 86%), MAGE-E1 (5/7 or 71%), followed by SSX-2 (2/7 or 29%) and SCP-1 (1/7 or 14%). However, 4 astrocytomas, 3 anaplastic astrocytomas, and 3 oligodendroglial tumors only expressed MAGE-E1 and SOX-6. Schwannomas also expressed SOX-6 (5/6 or 83%), MAGE-E1 (4/6 or 67%), and SCP-1 (2/6 or 33%). CONCLUSION: The data presented here suggest that MAGE-E1 and SOX-6 genes are expressed in a high percentage of human central nervous system tumors, which implies the CT genes could be the potential targets of immunotherapy for human central nervous system tumors.

Intracranial Fusiform Aneurysms: It's Pathogenesis, Clinical Characteristics and Managements.

OBJECTIVE: The objective of this study is to investigate clinical characteristics, management methods and possible causes of intracranial fusiform aneurysm. METHODS: Out of a series of 2,458 intracranial aneurysms treated surgically or endovascularly, 22 patients were identified who had discrete fusiform aneurysms. Clinical presentations, locations, treatment methods and possible causes of these aneurysms were analyzed. RESULTS: Ten patients of fusiform aneurysm were presented with hemorrhage, 5 patients with dizziness with/without headache, 4 with ischemic neurologic deficit, and 1 with 6th nerve palsy from mass effect of aneurysm. Two aneurysms were discovered incidentally. Seventeen aneurysms were located in the anterior circulation, other five in the posterior circulation. The most frequent site of fusiform aneurysm was a middle cerebral artery. The aneurysms were treated with clip, and/or wrapping in 7, resection with/without extracranial-intracranial (EC-IC) bypass in 6, proximal occlusion with coils with/without EC-IC bypass in 5, EC-IC bypass only in 1 and conservative treatment in 3 patient. We obtained good outcome in 20 out of 22 patients. The possible causes of fusiform aneurysms were regard as dissection in 16, atherosclerosis in 4 and collagen disease or uncertain in 2 cases. CONCLUSION: There is a subset of cerebral aneurysms with discrete fusiform morphology. Although the dissection or injury of internal elastic lamina of the cerebral vessel is proposed as the underlying cause for most of fusiform aneurysm, more study about pathogenesis of these lesions is required.

Mutational analysis of the NF2 gene in sporadic meningiomas by denaturing high-performance liquid chromatography.

The NF2 tumor suppressor gene, located in chromosome 22q12, is involved in the development of sporadic meningiomas of the nervous system. In order to evaluate the role of the NF2 gene in sporadic meningiomas, we analyzed the entire coding regions of the NF2 gene in a group of 42 sporadic meningiomas: 17 meningothelial, 11 transitional, 11 fibrous, one secretory, one atypical, and one malignant subtype, using denaturing high-performance liquid chromatography (DHPLC) and sequence analysis. Twenty-one mutations were identified in 20 patients with an overall mutation detection rate of 47.6%. The mutations included nine deletions (exons 1, 2, 5, 10, and 12), resulting in a frameshift, four non-sense mutations (exons 1, 2, and 7), four splice errors (exons 4, 5, 7, and 12), two missense mutations (exon 5) and two silent mutations (exon 11). Among these, 14 novel mutations were also identified in the present study. All mutations were noted in the first 12 exons, the region of homology with the ezrin-moesin-radixin protein. Furthermore, an association between NF2 mutations and histologic subtypes were observed; NF2 mutations were more frequent in fibrous meningiomas (8/11, 73%) and transitional meningiomas (6/11, 55%), than in meningothelial variant (5/17, 29%). These results provide evidence that mutations in the NF2 gene play an important role in the development of sporadic meningiomas as well as indicating a different tumorigenesis of these meningioma variants.

Traumatic aneurysm of the supraclinoid internal carotid artery and an associated carotid-cavernous fistula: vascular reconstruction performed using intravascular implantation of stents and coils. Case report.

This report documents the treatment of a traumatic aneurysm of the supraclinoid internal carotid artery (ICA) that was associated with a carotid-cavernous fistula (CCF), which appeared following closed head trauma. This life-threatening lesion, which is very rare, required aggressive management achieved using intravascular stents and coils. A 19-year-old man presented with severe traumatic intracerebral and subarachnoid hematoma after he had suffered a severe closed head injury in a motor vehicle accident. Cerebral angiography performed 11 days after the injury demonstrated a traumatic aneurysm and severe narrowing of the right supraclinoid ICA, which was consistent with a dissection-induced stenosis associated with a direct CCF. Both lesions were successfully obliterated with preservation of the parent artery by using stents in conjunction with coils. Follow-up angiography obtained 7 months postoperatively revealed persistent obliteration of the aneurysm and CCF as well as patency of the parent artery. The patient remained asymptomatic during the clinical follow-up period of 14 months. Endovascular treatment involving the use of a stent combined with coils appears to be a feasible, minimally invasive option for treatment of this hard-to-treat lesion.

Lateralization of epileptic foci by neuropsychological testing in mesial temporal lobe epilepsy.

This study investigated the lateralizing value of neuropsychological testing in presurgical evaluation of mesial temporal lobe epilepsy (MTLE). This study differed from previous ones in that the cutoff values were determined to yield high positive predictive values (PPVs), multiple neuropsychological predictors were considered in combination, and patients with atypical language dominance or low intelligence were not excluded from the sample. The participants were 92 patients with MTLE (left, n = 47; right, n = 45) who showed good postoperative seizure control. With a stringent cutoff criterion, the multiple neuropsychological predictors considered in combination yielded a sensitivity of 15% and a PPV of 93%, and with a less stringent cutoff criterion, a sensitivity of 37% and a PPV of 83%.

Differential effects of left versus right mesial temporal lobe epilepsy on Wechsler intelligence factors.

This study investigates the effects of left versus right mesial temporal lobe epilepsy (MTLE) on Wechsler intelligence factors. In the left MTLE group, the Verbal Comprehension (VC) factor score was significantly lower than the Perceptual Organization (PO) factor score, whereas in the right MTLE group, the PO factor score was significantly lower than the VC factor score. The VC factor score was significantly lower for the left than the right MTLE group, whereas the PO factor score was significantly lower for the right than the left MTLE group. Thus, left versus right MTLE was associated with relative deficits in verbal versus nonverbal intelligence, respectively. These findings indicate that lateralized cognitive deficits in unilateral MTLE patients are not limited to the learning-memory domain but include more global intelligence functions.

Material-specific memory in temporal lobe epilepsy: effects of seizure laterality and language dominance.

This study investigated the effects of seizure laterality and language dominance on material-specific memory in temporal lobe epilepsy (TLE). Left TLE (LTLE) patients with left-hemisphere language dominance (LHLD) showed significantly higher nonverbal than verbal memory capacity, whereas right TLE patients with LHLD showed significantly better verbal than nonverbal memory capacity. LTLE patients with non-left-hemisphere language dominance (NLHLD) showed significantly better verbal memory capacity compared with LTLE patients with LHLD. Thus, selective verbal or nonverbal memory deficits that are dependent on side of seizure onset were apparent in patients with LHLD but not in patients with NLHLD. Relative sparing of verbal memory capacity in LTLE patients with NLHLD may reflect interhemispheric reorganization of verbal memory function.

Immunohistochemical analysis for histopathological subtypes in pediatric medulloblastomas.

Medulloblastomas occurring in children represent a histological spectrum of varying anaplasia and nodularity. In order to determine whether immunohistochemical markers might be useful parameters in subclassifying these tumors, 17 pediatric medulloblastomas, including nine diffuse/non-anaplastic, four diffuse/anaplastic, three nodular/non-anaplastic and one nodular/anaplastic subtypes, were studied. In the present report, we investigate the expression of neural cell adhesion molecule (NCAM), nerve growth factor receptor (NGFR), neurofilament (NF), synaptophysin (SYN), glial fibrillary acidic protein (GFAP), S100, Bcl-2, and Ki-67 by using the immunohistochemistry against specific antibodies. This study showed that NGFR, NF, GFAP and S100 were not detected in anaplastic subtypes of medulloblastomas (0/5), while non-anaplastic subtypes were mainly expressed within the nodules. All 17 tumors were reactive for NCAM, SYN and Bcl-2. In addition, Ki-67 labeling indices for anaplastic subtypes (39.0 +/- 7.42%) were significantly higher than that of non-anaplastic medulloblastomas (11.4 +/- 8.04%; P < 0.0001). These results suggest that immunohistochemical markers are a useful adjunct in characterizing subtypes of pediatric medulloblastomas.

Merits of intralesional fibrin glue injection in surgery for cavernous sinus cavernous hemangiomas. Technical note.

In planning surgical treatment for extraaxial cavernous hemangiomas, care should be taken to control severe tumor bleeding. The authors present a case of a large cavernous hemangioma of the cavernous sinus, which was completely removed with the aid of multiple intratumoral injections of fibrin glue. This novel method is very effective for preventing excessive blood loss during surgery for this type of lesion.