川合 謙介

We compared electrocorticography (ECoG) with invasive intracranial noninvasive functional MRI using language-related tasks. Twenty patients underwent bilateral implantation of subdural electrodes (more than 80 channels) for diagnosing intractable epilepsy. Before implantation of the electrodes, language-related fMRI was performed, and the fMR images were superimposed on individual brain images. Brain mapping with electrocortical stimulation was performed on the basis of the fused fMR and brain MR images, and the specificity and sensitivity of language-related fMRI was calculated. For careful interpretation of spatial and temporal ECoG changes with semantic tasks, we developed a software to visualize semantic-ECoG dynamics in the brain. Semantic-ECoG was recorded during word, figure, and face recognition as well as memory tasks. The raw ECoG data were processed by averaging and time-frequency analysis, and the functional profiles were projected onto the individual brain surface. Acquired ECoG was classified using Support Vector Machine and Sparse Logistic Regression to decode brain signals. Because of variations in electrode locations, we normalized the ECoG electrodes by using SPM8. Although fMRI has 90% sensitivity, its specificity is only up to 50%. The basal temporal-occipital cortex was activated within 250 ms after visual object presentation. Compared to other stimuli, face stimulation evoked significantly higher ECoG amplitudes. Among different brain regions, the hippocampus was predominantly activated during the memory task. The prediction rate of ECoG classification was 90%, which was sufficient for clinical use. Semantic-ECoG is a powerful technique to detect and decode human brain functions.

Functional neuroimaging is one of the most progressing fields in neuroscience and clinical neurological practice. It has also been contributing to the diagnosis and treatment of epilepsy. Intracranial electroencephalography (iEEG) is the gold standard for the diagnostic localization of the epileptogenic zone in the surgical treatment of epilepsy. Currently, no other modalities, including novel functional neuroimaging modalities, are superior to ¡EEG in sensitivity and spatial resolution. However, iEEG is an invasive procedure and its clinical usefulness is dependent on appropriate coverage of the epileptogenic zone. In this review article, the author discusses the principles of decision making in surgical indication and procedures by presenting clinical cases and evaluating the significance of functional neuroimaging in these processes the review focuses on magnetoencephalography, 2-deoxy-2-[ 18F] fluoro-D-glucose positron emission tomography, and single photon emission computed tomography. The characteristics, advantages, and disadvantages of each modality are summarized. In some cases, but not all, functional neuroimaging modalities help avoid invasive iEEG without worsening surgical outcome and aid in determining the coverage area of iEEG, thereby resulting in better outcome and less complication.

Object. Techniques for the surgical treatment of meningioma have undergone many improvements since Simpson established the neurosurgical dogma for meningioma surgery in his seminal paper published in 1957. This study aims to assess the clinical significance and limitations of the Simpson grading system in relation to modern surgery for WHO Grade I benign meningiomas and to explore the potential of the cell proliferation index to complement the limitations in predicting their recurrence. Methods. The surgical records of patients who underwent resection of intracranial meningiomas at the University of Tokyo Hospital between January 1995 and August 2010 were retrospectively analyzed. The authors investigated the relationships between recurrence-free survival (RFS) and Simpson grade or MIB-1 labeling index value. Results. A total of 240 patients harboring 248 benign meningiomas were included in this study. Simpson Grade IV resection was associated with a significantly shorter RFS than Simpson Grade I, II, or III resection (p < 0.001), while no statistically significant difference was noted in RFS between Simpson Grades I, II, and III. Among meningiomas treated by Simpson Grade II and III resections, however, multivariate analysis revealed that an MIB-1 index of 3% or higher was associated with a significantly shorter time to recurrence. Conclusions. The clinical significance of the different management strategies related to Simpson Grade I-III resection may have been diluted in the modern surgical era. The MIB-1 index can differentiate tumors with a high risk of recurrence, which could be beneficial for planning tailored optimal follow-up strategies. The results of this study appear to provide a significant backing for the recent shift in meningioma surgery from attempting aggressive resection to valuing the quality of the patient's life. (http://thejns.org/doi/abs/10.3171/2012.3.JNS111945)

Object. Despite the controversy over the clinical significance of Gamma Knife surgery (GKS) for refractory mesial temporal lobe epilepsy (MTLE), the modality has attracted attention because it is less invasive than resection. The authors report long-term outcomes for 7 patients, focusing in particular on the long-term complications. Methods. Between 1996 and 1999,7 patients with MTLE underwent GKS. The 50% marginal dose covering the medial temporal structures was 18 Gy in 2 patients and 25 Gy in the remaining 5 patients. Results. High-dose treatment abolished the seizures in 2 patients and significantly reduced them in 2 others. One patient in this group was lost to follow-up. However, 2 patients presented with symptomatic radiation necrosis (SRN) necessitating resection after 5 and 10 years. One patient who did not need necrotomy continued to show radiation necrosis on MRI after ID years. One patient died of drowning while swimming in the sea 1 year after GKS, before seizures had disappeared completely. Conclusions. High-dose treatment resulted in sufficient seizure control but carried a significant risk of SRN after several years. Excessive target volume was considered as a reason for delayed necrosis. Drawbacks such as a delay in seizure control and the risk of SRN should be considered when the clinical significance of this treatment is evaluated. (http://thejns.org/doi/abs/10.3171/2012.2.JNS111296)

Vagus nerve Stimulation (VNS) is a palliative treatment for medically intractable epilepsy and has been covered by public health insurance in Japan since July 1, 2010. The frequency of the use of VNS during the first year of insurance coverage was determined by assessing the number of cases for which VNS was performed in Kyushu Rosai Hospital, the number of registered cases, and the questionnaire survey filled by 68 surgeons who are board certified as both epileptologists and neurosurgeons. VNS devices were placed in 98 patients from July 2010 to June 2011. These devices were placed in an average of 4.4 patients per month from July 2010 to November 2010 and in an average of 10.9 patients from December 2010 to June 2011. However, we did not observe an increasing trend. Almost all of the surgeries were performed in the Kanto (56 patients in 8 institutes) and Tokai (24 patients in 2 institutes) areas. VNS was not performed in many institutes primarily because VNS was not indicated for any of the patients. The questionnaire survey indicated that the use of VNS was likely to increase with an increase in the number of neurologists who decide on performing VNS preoperatively and regulate the conditions of the vagus nerve stimulator postoperatively. In conclusion, VNS is currently being applied in a limited number of institutes in the Kanto and Tokai areas, and a close association between the epileptologists and neurologists during preoperative and postoperative periods will increase the use of VNS.

Inter-ictal F-18-2-fluoro-deoxy--glucose-positron emission tomography (FDG-PET) is widely used for preoperative evaluation to identify epileptogenic zones in patients with temporal lobe epilepsy. In this study, we combined statistical parametric mapping (SPM) with the asymmetry index and volume-of-interest (VOI) based extent analysis employing preoperative FDG-PET in unilateral mesial temporal lobe epilepsy (MTLE) patients. We also evaluated the detection utility of these techniques for automated identification of abnormalities in the unilateral hippocampal area later confirmed to be epileptogenic zones by surgical treatment and subsequent good seizure control. FDG-PET scans of 17 patients (9 males, mean age 35 years, age range 16-60 years) were retrospectively analyzed. All patients had been preoperatively diagnosed with unilateral MTLE. The surgical outcomes of all patients were Engel class 1A or 1B with postoperative follow-up of 2 years. FDG-PET images were spatially normalized and smoothed. After two voxel-value adjustments, one employing the asymmetry index and the other global normalization, had been applied to the images separately, voxel-based statistical comparisons were performed with 20 controls. Peak analysis and extent analysis in the VOI in the parahippocampal gyrus were conducted for SPM. For the extent analysis, a receiver operating characteristic (ROC) curve was devised to calculate the area under the curve and to determine the optimal threshold of extent. The accuracy of the method employing the asymmetry index was better than that of the global normalization method for both the peak and the extent analysis. The ROC analysis results, for the extent analysis, yielded an area under the curve of 0.971, such that the accuracy and optimal extent threshold of judgment were 92 and 32.9%, respectively. Statistical -score mapping with the asymmetry index was more sensitive for detecting regional glucose hypometabolism and more accurate for identifying the side harboring the epileptogenic zone using inter-ictal FDG-PET in unilateral MTLE than -score mapping with global normalization. Moreover, the automated determination of the side with the epileptogenic zone in unilateral MTLE showed improved accuracy when the combination of SPM with the asymmetry index and extent analysis was applied based on the VOI in the parahippocampal gyrus.

Malignant change in fibrous dysplasia (FD) is a well-described phenomenon in the literature. When rapid enlargement is observed in an FD lesion, malignant change should be considered first. We present a case with McCune-Albright syndrome in which a rapidly enlarging orbital tumor developed in a facial FD lesion, which was subsequently proven to be a metastasis from an incidental esophageal carcinoma. Although metastasis of a malignant tumor to an FD lesion is quite rare and has been neglected as a differential diagnosis in the literature, it should be included in the important differential diagnosis because hematogenous metastasis could readily occur in FD due to its abundant blood flow. The importance of systemic examinations, such as positron emission tomography, is also emphasized. © 2012 by Lippincott Williams &amp Wilkins.

BACKGROUND: Functional magnetic resonance imaging (fMRI) is a less invasive way of mapping brain functions. The reliability of fMRI for localizing language-related function is yet to be determined. OBJECTIVE: We performed a detailed analysis of language fMRI reliability by comparing the results of 3-T fMRI with maps determined by extraoperative electrocortical stimulation (ECS). METHODS: This study was performed on 8 epileptic patients who underwent subdural electrode placement. The tasks performed during fMRI included verb generation, abstract/concrete categorization, and picture naming. We focused on the frontal lobe, which was effectively activated by these tasks. In extraoperative ECS, 4 tasks were combined to determine the eloquent areas: spontaneous speech, picture naming, reading, and comprehension. We calculated the sensitivity and specificity with different Z score thresholds for each task and appropriate matching criteria. For further analysis, we divided the frontal lobe into 5 areas and investigated intergyrus variations in sensitivity and specificity. RESULTS: The abstract/concrete categorization task was the most sensitive and specific task in fMRI, whereas the picture naming task detected eloquent areas most efficiently in ECS. The combination of the abstract/concrete categorization task and a 3-mm matching criterion gave the best tradeoff (sensitivity, 83%; specificity, 61%) when the Z score was 2.24. As for intergyrus variation, the posterior inferior frontal gyrus showed the best tradeoff (sensitivity, 91%; specificity, 59%), whereas the anterior middle frontal gyrus had low specificity. CONCLUSION: Despite different tasks for fMRI and extraoperative ECS, the relatively low specificity might be caused by a fundamental discrepancy between the 2 techniques. Reliability of language fMRI activation might differ, depending on the brain region.

Documentation of familial epilepsy is of paramount importance for identification of epilepsy-associated genes, elucidation of pathomechanisms of epilepsy, and development of treatment of epilepsy. We report a Japanese family with 5 members with lateral temporal lobe epilepsy beginning around the second decade of life. All seizures were intractable to medical treatment, and four patients underwent surgical treatment following long-term monitoring by intracranial electroencephalography with subdural electrodes, which revealed neocortical origins for the seizure. These four patients were successfully treated with surgery. The clinical features of this familial temporal lobe epilepsy seem to be different from those of previously reported types of familial temporal lobe epilepsy.

Background. Tumor-induced osteomalacia (TIO) is a rare clinical entity in which secondary osteomalacia is induced by tumor-related products. Fibroblast growth factor 23 (FGF-23) mRNA is overexpressed in the tumor tissue, leading to impaired reabsorption of phosphorus in the renal tubules and hypophosphatemia. Curative treatment is considered to be total resection of the tumor. Methods and Results. A 53-year-old woman had experienced systemic bone pain and muscle weakness for several years. She had refractory hypophosphatemia and marked elevation of serum FGF-23 level. Whole body imaging eventually revealed a hypervascular mass in the right temporal bone, leading to a diagnosis of TIO. She underwent skull-base surgery after embolization of the tumor. After the en bloc resection, FGF-23 became undetectable, phosphate reabsorption normalized, and all symptoms resolved. Conclusions. We discuss the clinical features and treatment options for this rare disease. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 1072-1075, 2011

BACKGROUND AND IMPORTANCE: Tumor-induced osteomalacia (TIO) is an uncommon paraneoplastic syndrome rarely encountered in neurosurgical practice. We report on 2 cases of TIO caused by skull base tumors. Although the diagnosis of TIO is difficult to make and often is delayed because of the insidious nature of the symptoms, mostly systemic pain and weakness, it is curable once it is diagnosed and properly treated. CLINICAL PRESENTATION: Both patients presented with severe pain developing in the lower extremities and moving out to the entire body, as well as difficulty moving. They were diagnosed with TIO several years after onset. A high level of serum FGF23 was confirmed, and whole-body imaging studies demonstrated tumors in the middle and anterior cranial base, respectively. The patient with the anterior cranial base tumor had a history of hemorrhage into the frontal lobe and partial resection. En bloc resection of tumor with surrounding skull bone was performed. The histological diagnosis for both cases was phosphaturic mesenchymal tumor, mixed connective tissue variant. CONCLUSION: The level of FGF23 normalized immediately after surgery. Both patients experienced a dramatic relief of pain and recovery of muscle power. Although reports of osteomalacia caused by tumors in the neurosurgical field are extremely rare in the literature, its true incidence is unknown. We emphasize the importance of recognition of this syndrome and recommend total resection of tumors when possible.

Electrocorticography (ECoG), multichannel brain-surface recording and stimulation with probe electrode arrays, has become a potent methodology not only for clinical neurosurgery but also for basic neuroscience using animal models. The highly evolved primate's brain has deep cerebral sulci, and both gyral and intrasulcal cortical regions have been implicated in important functional processes. However, direct experimental access is typically limited to gyral regions, since placing probes into sulci is difficult without damaging the surrounding tissues. Here we describe a novel methodology for intrasulcal ECoG in macaque monkeys. We designed and fabricated ultra-thin flexible probes for macaques with micro-electro-mechanical systems (MEMS) technology. We developed minimally invasive operative protocols to implant the probes by introducing cutting edge devices for human neurosurgery. To evaluate the feasibility of intrasulcal ECoG, we conducted electrophysiological recording and stimulation experiments. First, we inserted parts of the Parylene-C-based probe into the superior temporal sulcus to compare visually evoked ECoG responses from the ventral bank of the sulcus with those from the surface of the inferior temporal cortex. Analyses of power spectral density and signal-to-noise ratio revealed that the quality of the ECoG signal was comparable inside and outside of the sulcus. Histological examination revealed no obvious physical damage in the implanted areas. Second, we placed a modified silicone ECoG probe into the central sulcus and also on the surface of the precentral gyrus for stimulation. Thresholds for muscle twitching were significantly lower during intrasulcal stimulation compared to gyral stimulation. These results demonstrate the feasibility of intrasulcal ECoG in macaques. The novel methodology proposed here opens up a new frontier in neuroscience research, enabling the direct measurement and manipulation of electrical activity in the whole brain. © 2011 Matsuo, Kawasaki, Osada, Sawahata, Suzuki, Shibata, Miyakawa, Nakahara, Iijima, Sato, Kawai, Saito and Hasegawa.

Objective. The determination of language lateralisation is important for patients with medically intractable epilepsy or a brain tumour near the language areas to avoid the risk of post-surgical language deficits. The aim of this study was to evaluate the clinical usefulness of near-infrared spectroscopy (NIRS) to identify language lateralisation compared with functional MRI (fMRI) and magnetoencephalography (MEG) in multiple language tasks. Methods. We investigated 28 patients whose language dominance was evaluated by the Wada test. fMRI, MEG and NIRS were performed to investigate language representation. All patients were as'ked to read three-letter words silently for fMRI and MEG (Kana reading) and to write words beginning with a visually presented letter (word generation) for NIRS. The laterality index was calculated to assess language lateralisation in each investigation. Results. In 24 cases (85.7%), of which two investigations showed the same laterality, the results had perfect concordance with the Wada test. In patients with left dominance, the sensitivity and specificity of fMRI, MEG and NIRS was 95.0% and 62.5%, 100% and 87.5%, 75.0% and 87.5%, respectively. In three patients with right lateralization, only NIRS showed a significant increase of oxygenated-haemoglobin in the right inferior frontal region, indicating right dominance. Conclusion. We established a method to determine language lateralisation by co-utilising fMRI, MEG and NIRS with high reliability. NIRS recognised atypical language representation, in addition to fMRI and MEG. While fMRI, MEG and NIRS are not currently as accurate as the Wada test in determining language lateralisation, this non-invasive and repeatable method has great potential as an alternative to the Wada test in time following further research and refinement of these techniques.

Vagus nerve stimulation is a palliative treatment for medically intractable epilepsy. This treatment reduces the frequency and severity of seizures refractory to antiepileptic drugs. Implanted generator and helical electrodes electrically stimulate the left vagus nerve at the neck chronically and intermittently. This was the first electrostimulation therapy clinically introduced for epilepsy. This treatment approach is supported by randomized double-blind trials even though the anti-seizure effect of vagus nerve stimulation is palliative and not curative. In Western countries, particularly the United States, this therapy has become an important alternative treatment for a subpopulation of patients with drug-resistant seizures who are not good candidates for craniotomy. In Japan, vagus nerve stimulation therapy was finally approved in January 2010 and has been covered by public health insurance since July 2010. Here, the author reviews the history, efficacy, and safety of this treatment, surgical anatomy and physiology of the vagus nerve, and the putative mechanisms underlying inhibition of epileptic seizures and accompanying effect on the central nervous system. Further experimental and clinical studies regarding this treatment approach are required to elucidate the detailed mechanism of action, to clarify the predicting factors of favorable outcome, and to scientifically confirm the anti-seizure effect in children and in generalized seizures and the efficacy in improvement of cognitive function, development, and quality of life.

Vagus nerve stimulation is the first electrical stimulation therapy for epilepsy. While its clinical use was approved by the European Union in 1994 and by the United States in 1997, it was approved last year and coverage by public insurance started last July in Japan. Owing to less invasiveness and broad indication, it is expected that vagus nerve stimulation will be increasingly used in Japan as well. Its efficacy for refractory partial seizures in patients older than 13 years was validated by two randomized control trials. Although it has been used for children and generalized seizures broadly, the efficacy for these subpopulations of patients has not been validated by randomized control trials, necessitating those studies in the near future. Afferent neural impulses generated by vagus nerve stimulation transmit to the solitary tract nucleus, then via multiple pathways including the monoamine system, vagus nerve stimulation affects the excitability of the cortical neurons. It likely exerts the anti-epileptic and anti-seizure effects using these pathways, but the detailed mechanisms underlying the effect remains to be elucidated further in future.

Object. Intraoperative monitoring of visual evoked potentials (VEPs) has been regarded as having limited significance for the preservation Of Visual function during neurosurgical procedures, mainly due to its poor spatial resolution and signal-to-noise ratio. The authors evaluated the usefulness of cortically recorded VEPs, instead of the usual scalp VEPs, as intraoperative monitoring focusing on the posterior Visual pathway. Methods. In 17 consecutive patients who underwent microsurgical procedures for lesions near the posterior visual pathway, cortical responses were recorded using 1-Hz flashing light-emitting diodes and subdural strip electrodes after induction of general anesthesia with sevoflurane or propofol. The detectability and waveform of the initial response, stability, and changes during microsurgical manipulations were analyzed in association with the position of electrodes and postoperative changes in Visual function. Results. Initial VEPs were detected in 82% of all patients. The VEPs were detected in 94% of patients without total hemianopia in whom electrodes were placed sufficiently near the occipital pole; in these cases the recordings were not significantly affected by anesthesia. The detectability rates of the negative peak before 100 msec (NI), positive peak similar to 100 msec (P100), and negative peak after 100 msec (N2) were 36, 50, and 100%, respectively. The mean latencies and amplitudes of N1, P100, and N2 were 90.0 +/- 15.9 msec and 61.0 +/- 64.0 mu V, 103.9 +/- 13.5 msec and 34.3 +/- 38.6 mu V, and 125.7 +/- 12.2 msec and 44.9 +/- 48.9 mu V, respectively, showing great variability. In 11 patients, the initial waveforms of VEP remained stable during microsurgical procedures, and the visual status did not change postoperatively, while it disappeared in 2 patients who presented with postoperative hemianopia. Conclusions. Direct recording from the visual cortices under general anesthesia achieved satisfactory detectability of the visual response to a light-emitting diode flashing light. Although the initial waveforms varied greatly among patients, they were stable during microsurgical procedures, and the changes were consistent with postoperative visual function. Intraoperative cortical VEP monitoring is a potentially useful procedure to monitor the functional integrity of the posterior Visual pathway. (DOI: 10.3171/2009.6.JNS081272)

Object. To validate the corticospinal tract (CST) illustrated by diffusion tensor imaging, the authors used tractography-integrated neuronavigation and direct fiber stimulation with monopolar electric currents. Methods. Forty patients with brain lesions adjacent to the CST were studied. During the operation, the motor responses (motor evoked potential [MEP]) elicited at the hand by the cortical stimulation to the hand motor area were continuously monitored, maintaining the consistent stimulus intensity (mean 15.1 +/- 2.21 mA). During lesion resection, direct fiber stimulation was applied to elicit MEP (referred to as fiber MEP) to identify the CST functionally. The threshold intensity for the fiber MEP was determined by searching for the best stimulus point and changing the stimulus intensity. The minimum distance between the resection border and illustrated CST was measured on postoperative isotropic images. Results. Direct fiber stimulation demonstrated that tractography accurately reflected anatomical CST functioning. There were strong correlations between stimulus intensity for the fiber MEP and the distance between the CST and the stimulus points. The results indicate that the minimum stimulus intensity of 20, 15, 10, and 5 mA had stimulus points similar to 16, 13.2, 9.6, and 4.8 mm from the CST, respectively. The convergent calculation formulated 1.8 mA as the electrical threshold of the CST for the fiber MEP, which was much smaller than that of the hand motor area. Conclusions. The investigators found that diffusion tensor imaging-based tractography is a reliable way to map the white matter connections in the entire brain in clinical and basic neuroscience applications. By combining these techniques, investigating the cortical-subcortical connections in the human CNS could contribute to elucidating the neural networks of the human brain and shed light on higher brain functions. (DOI: 10.3171/2008.9.JNS08414)

we present a patient with multilobar cortical dysplasia who underwent hemispherotomy, a modified functional hemispherectomy, at the age of 2 months because of intractable seizures and report the clinical-neurophysiological findings including EEG and somatosensory evoked potentials (SEP). After hemispherotomy, the seizures and EEG abnormality disappeared completely and postoperative SEP showed an ipsilateral cortical response at the unaffected hemisphere, suggesting a reorganization process, which was possibly facilitated more intensively after surgery. Furthermore, developmental catch-up was observed. our patient's clinical course and neurophysiological data suggested that very early hemispherotomy resulted in not only the control of seizures but also a better developmental outcome. (C) 2008 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Vagus nerve stimulation (VNS) and stereotactic radiosurgery (SRS) represent novel and less invasive therapeutics for medically intractable epilepsy. VNS ushered in the recent advancement in clinical application of electrical stimulation therapy for epilepsy. Chronic stimulation of the left vagus nerve with implanted generator and electrodes inhibits seizure susceptibility of the cerebral cortices. Its efficacy and safety have been established by randomized clinical trials in 1990s in the Western countries and it has been widely accepted as a treatment option for patients with medically intractable epilepsy for whom brain surgery is not indicated or failed. Although the effect on seizures is not so dramatic, the less invasiveness and a wide range of indication have made VNS indispensable for comprehensive care of epilepsy. Since the devices are not approved for clinical use in Japan, there exist barriers to provide VNS to patients at present. Use of SRS for intractable epilepsy started in mid 90s as gamma knife surgery for mesial temporal lobe epilepsy. The marginal dose of 25 Gy to the medial temporal structures has been confirmed to be effective for seizure control, but there seems to be an unignorable risk of brain edema and radiation necrosis. It is still controversial whether the therapy is more effective and less invasive than brain surgery. A randomized clinical trial using the dose of 20 or 24 Gy is ongoing in the United States. SRS for intractable epilepsy associated with hypothalamic hamartoma has been advocated because of a high surgical morbidity, but further study is needed for standardization of the treatment. Substitute use of SRS for other surgical technique like callosotomy or disconnection of epileptic focus seems to be another direction worth pursuing.

OBJECTIVE: It is known that functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) are sensitive to the frontal and temporal language function, respectively. Therefore, we established combined use of fMRI and MEG to make reliable identification of the global language dominance in pathological brain conditions. METHODS: We investigated 117 patients with brain lesions whose language dominance was successfully confirmed by the Wada test. All patients were asked to generate verbs related to acoustically presented nouns (verb generation) for fMRI and to read three-letter words for fMRI and MEG. RESULTS: fMRI typically showed prominent activations in the inferior and middle frontal gyri, whereas calculated dipoles on MEG typically clustered in the superior temporal region and the fusiform gyrus of the dominant hemisphere. A total of 87 patients were further analyzed using useful data from both the combined method and the Wada test. Remarkably, we observed a 100% match of the combined method results with the results of the Wada test, including two patients who showed expressive and receptive language areas dissociated into bilateral hemispheres. CONCLUSION: The results demonstrate that this non-invasive and repeatable method is not only highly reliable in determining language dominance, but can also locate the expressive and receptive language areas separately. The method may be a potent alternative to invasive procedures of the Wada test and useful in treating patients with brain lesions.

Despite good seizure outcome with temporal lobectomy, postoperative impairment of verbal memory remains unsolved. To address this problem we developed a new method, applying the rationale of multiple subpial transection (MST) to the hippocampus. The inferior ventricle is accessed without disrupting the neuronal pathways related to verbal memory. Intraoperative electrocorticography is recorded over the hippocampus and amygdala. After the extent of the epileptic area is determined, multiple transections of the pyramidal layer under the alveus is performed using specially designed ring transectors. After this procedure, epileptic discharges from the hippocampus can be completely abolished. Of 21 cases undergoing this operation, 12 left-sided and nine right-sided, 17 were followed up for more than one year. Fourteen (82%) are seizure free, two (12%) have rare seizures, and one (6%) has significantly improved. Of eight patients who underwent a battery of neuropsychometric tests both before and after left hippocampal transection, postoperative verbal memory was completely preserved in seven cases, and one transiently worsened patient recovered within 6 months. However, these results are still preliminary as the number of patients is small and the follow-up time short. The accumulation of cases and follow-up of greater duration will be necessary to precisely confirm the efficacy of this new technique. (C) 2006 Elsevier Ltd. All rights reserved.

OBJECTIVE: It has been difficult to obtain anatomic and functional information about the visual pathway during neurosurgical operations. The aim of this study was to combine the information of the visual evoked potentials (VEPs) and the anatomic navigation of the optic radiation by diffusion tensor imaging-based tractography for functional monitoring of the visual pathway. METHODS: The subjects were two patients with brain lesions adjacent to the visual pathway. Diffusion tensor imaging-based tractography of the optic radiation was performed by selecting appropriate regions of interest and by fractional anisotropy. During surgery, cortical VEPs were recorded continuously under general anesthesia with sevoflurane. In Patient 2, the results of optic radiation tractography were imported to a neuronavigation system to better understand the spatial relationships between the lesions and the visual pathway (functional neuronavigation). RESULTS: In Patient 1, the lesion did not seem to be attached to the optic radiation, and VEP profiles remained stable during resection. In Patient 2, who had a lesion adjacent to the posterior horn of the lateral ventricle, VEPs suddenly diminished when resection reached the optic radiation as illustrated on the neuronavigation system. AS a result, complete left hemianopia developed after surgery in Patient 2. CONCLUSION: We confirmed functional correlations of the results of diffusion tensor imaging-based tractography by monitoring intraoperative VEPs. The combination of continuous VEP and optic-radiation tractography is reliable to monitor the visual function and is helpful in performing neurosurgical planning near the visual pathway.

We recorded human orbitofrontal electrocorticogram during wakefulness and sleep in epileptic patients using subdural electrodes. During wakefulness and rapid eye movement (REM) sleep, we observed beta activity in the raw orbitofrontal signals. Power spectral analysis demonstrated beta enhancement during wakefulness and REM sleep when compared to slow wave sleep (SWS). During the phasic REM periods, the beta power was significantly lower than during the tonic REM periods. Gamma enhancement manifested itself in four out of six subjects during the phasic periods. This study is the first that has focused on electrical activity in the human orbitofrontal cortex. Although the role of the orbitofrontal cortex during sleep still remains unclear, high frequency activities give us important suggestions in elucidating the human sleep mechanism. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

Ten epileptic patients each with subdural electrodes surgically attached to the anterior cingulate cortex (ACC; two cases), the orbitofrontal cortex (OFC: seven cases), or both (one case) were included in this study. We recorded each patient's ACC or OFC electrocorticogram (ECoG) during the time period that the patient was awake and naturally asleep. We performed a Fast Fourier Transformation (FFT) power spectral analysis on each ECoG to examine its frequency component. We found that the ACC showed regular and continuous theta oscillation (5-7Hz) during wakefulness and rapid eye movement (REM) sleep, but not during slow wave sleep. Theta waves observed in REM sleep were not as distinct as those found in wakefulness. We also discovered that the orbitofrontal signals represented spectral peaks in the theta band only during wakefulness. This suggests the coexistence of theta oscillation in the ACC. Considering our previous observations of gamma and beta oscillations in the human hippocampus, we hypothesize that the human limbic system manifests two oscillatory activities. The results obtained in this study suggest that electrophysiological activity in the ACC could be related to particular psychological functions in wakefulness and in REM sleep. These results are useful in elucidating the human brain mechanism. (C) 2004 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Temporal lobe epilepsy is frequently drug-resistant in adult epilepsy. However, its surgical treatment is very effective and about 70% of operated patients become seizure-free. As preoperative evaluation, analysis of seizure characteristics, scalp EEG with sphenoidal lead, and neuroimaging are most important. When these noninvasive examinations are concordant in focus localization, surgical treatment without prolonged recording by intracranial electrodes become feasible. In spite of good seizure outcome after temporal lobectomy, postoperative impairment of verbal memory has remained to be a long-standing problem. To cope with this ominous complication, we developed a new surgical method of hippocampal transection, based on the principle of multiple subpial transection (MST). Placing a small corticotomy on the anterior part of superior temporal gyrus, the inferior ventricle is opened through suctioning the temporal stem. Intraoperative electrocorticography (ECoG) is recorded over the hippocampus. After the extent of the epileptic area is determined, the alveus is cut with microscissors and the pyramidal layer is transected in parallel with neuronal fibers by a specially designed ring transector. With this procedure, epileptic discharges from the hippocampus can be completely abolished. In all 7 cases undergoing left hippocampal transection, postoperative verbal memory was preserved with excellent seizure outcome.

The purpose of this study is to propose and investigate a new approach for discriminating between focal and non-focal hemispheres in intractable temporal lobe epilepsy, based on applying multivariate time series analysis to the discharge-free background brain activity observed in nocturnal electrocorticogram (ECoG) time series. Five unilateral focal patients and one bilateral focal patient were studied. In order to detect the location of epileptic foci, linear multivariate autoregressive (MAR) models were fitted to the ECoG data; as a new approach for the purpose of summarizing these models in a single relevant parameter, the behaviour of the corresponding impulse response functions was studied and described by an attenuation coefficient. In the majority of unilateral focal patients, the averaged attenuation coefficient was found to be almost always significantly larger in the focal hemisphere, as compared to the non-focal hemisphere. Also the amplitude of the fluctuations of the attenuation coefficient was significantly larger in the focal hemisphere. Moreover, in one patient showing a typical regular sleep cycle, the attenuation coefficient in the focal hemisphere tended to be larger during REM sleep and smaller during Non-REM sleep. In the bilateral focal patient, no statistically significant distinction between the hemispheres was found. This study provides encouraging results for new investigations of brain dynamics by multivariate parametric modeling. It opens up the possibility of relating diseases like epilepsy to the properties of inconspicuous background brain dynamics, without the need to record and analyze epileptic seizures or other evidently pathological waveforms. (C) 2004 Elsevier B.V. All rights reserved.

Object. Epilepsy in patients with bihemispheric malformations of cortical development (MCD) is typically medically intractable. Focal resection has been reported to be ineffective. Corpus callosotomy has been advocated as a treatment option, but the results have been reported only in several case reports. The authors describe a series of 10 patients with biltemispheric MCDs who underwent total corpus callosotomy. Methods. The MCDs in these patients included lissencephaly, band heterotopia, perisylvian polymicrogyria, and tuberous sclerosis. Preoperatively all patients suffered disabling drop attacks or intense head drop seizures that caused frequent physical injuries. The follow-up period ranged from 1.4 to 5.8 years (median 3.2 years). Seizure outcome, parental assessment of daily function, and parental satisfaction with outcome were assessed postoperatively. Drop attacks disappeared completely during the entire follow-up period in eight patients and decreased to less than 10% of baseline in one. Other types of seizures were resolved completely in one patient and decreased in seven. Overall daily function improved and parents were satisfied with the surgery-related results in all patients except one who experienced a recurrence of drop attacks. There were no signs of significant and persistent neurological deficits in any case. Conclusions. Results of total corpus callosotomy in patients with bihemispheric MCDs were favorable in most cases. The procedure was particularly effective against drop attacks causing physical injuries and impaired quality of life in these patients.

Purpose: We assessed the diagnostic value of [C-11]methionine (MET) positron emission tomography (PET) in the differential diagnosis of dysembryoplastic neuroepithelial tumors (DNETs) among benign tumors associated with temporal lobe epilepsy (TLE). Methods: This series consisted of seven TLE patients with benign tumors in the temporal lobe. After MET-PET study, all seven patients underwent tumor resection along with focus excision. The uptake of tracers was evaluated by the lesion-to-contralateral ratio (L/C ratio) and the standardized uptake value (SUV). We also assessed the relation between MET uptake and proliferation capacity observed in the surgical specimens. Results: Whereas four patients with DNETs did not show high MET uptake visually, the ganglioglioma and gliomas of the remaining three patients were identified as high-MET-uptake lesions. In the DNETs, the SUV ranged from 1.03 to 1.41, and the L/C ratio ranged from 0.99 to 1.14. MET uptake was significantly lower in the patients with DNETs than in the patients with ganglioglioma and brain gliomas (SUV, p=0.045; L/C ratio, p=0.0079). The Ki-67 labeling index was 4% in one patient with DNET and 5% in one patient with pleomorphic xanthoastrocytoma (higher labeling index). The higher labeling index was not related to high MET uptake based on the SUV (p=0.91) and L/C ratio (p=0.38). Conclusions: Negative MET uptake in benign temporal lobe tumors with TLE is consistent with a preoperative diagnosis of DNET.

Object. The intraluminal suture model for focal cerebral ischemia is increasingly used, but not without problems. It causes hypothalamic injury, subarachnoid hemorrhage, and inadvertent premature reperfusion. The patency of the posterior communicating artery (PCoA) potentially affects the size of the infarct. In addition, survival at I week is unstable. The authors operated on C57Black6 mice to produce proximal middle cerebral artery occlusion (MCAO) so that drawbacks with the suture model could be Circumvented. Methods. The MCA segment just proximal to the olfactory branch was occluded either permanently or temporarily. After I hour of MCAO the infarct volume was significantly smaller than that found after 2 hours or in instances of permanent MCAO. The differences were assessed at 24 hours and 7 days after surgery (p < 0.05 and p < 0.001, respectively). The patency of the PCoA, as visualized using carbon black solution, did not correlate with the infarct size. Neurologically, the 1 - and 2-hour MCAO groups displayed significantly less severe deficits than the permanent MCAO group on Days 1, 4, and 7 (p < 0.005 and p < 0.01, respectively). Although the infarct size, neurological deficits, and body weight loss were more severe in the permanent MCAO group, the survival rate at Day 7 was 80%. Conclusions. This model provides not only a robust infarct size (which is not affected by the patency of the PCoA), but also a better survival rate.

In previous studies we observed gamma (30-150 Hz) and beta-1 (10-20 Hz) oscillations in the medial temporal lobe (MTL) using subdural electrodes. The beta-1 was present during wake and REM sleep while gamma was present in all states. Recently we studied a patient (35 years M) with electrodes attached to the anterior cingulate cortex (ACC). This structure showed regular theta (5-6 Hz) oscillations. In the first recording, electrodes were attached to the MTL, that demonstrated the beta-1 and gamma oscillations. Two months later, electrodes were placed on orbitofrontal and ACC and an all night sleep recording was carried out. The ACC exhibited a highly regular and continuous theta oscillation during wakefulness and REM sleep, but not during NREM sleep. Since this same subject showed beta-1 oscillations in the MTL, it is probable that the theta in the ACC is independent of beta-1 in the MTL. This single case suggests the existence of two different frequency oscillators in the human limbic system. Elucidating their functional roles will be an interesting challenge for future studies.

In previous studies we observed gamma (30-150 Hz) and beta-1 (10-20 Hz) oscillations in the medial temporal lobe (MTL) using subdural electrodes. The beta-1 was present during wake and REM sleep while gamma was present in all states. Recently we studied a patient (35 years M) with electrodes attached to the anterior cingulate cortex (ACC). This structure showed regular theta (5-6 Hz) oscillations. In the first recording, electrodes were attached to the MTL, that demonstrated the beta-1 and gamma oscillations. Two months later, electrodes were placed on orbitofrontal and ACC and an all night sleep recording was carried out. The ACC exhibited a highly regular and continuous theta oscillation during wakefulness and REM sleep, but not during NREM sleep. Since this same subject showed beta-1 oscillations in the MTL, it is probable that the theta in the ACC is independent of beta-1 in the MTL. This single case suggests the existence of two different frequency oscillators in the human limbic system. Elucidating their functional roles will be an interesting challenge for future studies. (C) 2003 Elsevier Science Ltd. All rights reserved.

To investigate the sleep spindle activity of the human prefrontal cortex (PFC), we simultaneously recorded whole nights of polysomnographic and electrocorticographic (ECoG) activities during the natural sleep of epileptic patients. Subjects were nine patients with intractable epilepsy who had subdural electrodes surgically attached to the orbital (seven cases), medial (three cases), or dorsolateral (two cases) PFC, and in one case to the frontal pole. To examine spindle frequencies, fast Fourier transformation (FFT) and auto-correlation analyses were performed on the PFC ECoG and Cz EEG data, primarily on epochs of stage 2 sleep. Lower sigma band ECoG oscillations of about 12 Hz were widely distributed across all prefrontal cortical areas including the frontal limbic regions, but none of the PFC sigma frequency peaks coincided with the faster (about 14 Hz) Cz EEG sleep spindles. Combining our results with anatomical and electrophysiological facts, it is suggested that the thalamofrontal circuit involving the rostral reticular and the mediodorsal nucleus of the thalamus is responsible for the generation of 12 Hz frontal spindles in humans. (C) 2003 Elsevier Science Ireland Ltd. and the Japan Neuroscience Society. All rights reserved.

The outcome of long-term vagus nerve stimulation (VNS) was evaluated in 13 Japanese patients with intractable epilepsy, all followed up for more than 4 years (48-91 months, median 56 months). VNS achieved a long-lasting and cumulative seizure-control effect in nine of 13 patients. The mean reduction of seizure frequency in the 1st to 4th year was 28%, 47%, 54%, and 63%, respectively. The percentage of patients with >60% seizure reduction in the 1st to 4th year was 15%, 46%, 54%, and 69%, respectively. One patient did not respond to the treatment at all. No patient became completely free from seizure or free from medication, but the number and/or dosage of antiepileptic drugs was reduced in five patients. Ten patients underwent exchange of the generator and continued treatment, and two patients underwent removal of the generator because of the unsatisfactory result. VNS controlled more disabling seizures earlier and more efficiently than less disabling seizures in seven patients. The cumulative reduction of seizures was partly associated with changes in the device setting toward increased stimulation. These effects were similar in patients with or without previous resective surgery. Long-term VNS therapy achieved a favorable outcome in a significant proportion of patients with intractable epilepsy.

The cause of Ammon's horn sclerosis in temporal lobe epilepsy has not yet been clarified. In the present study, the pathological effect of epileptic seizures on the hippocampus was investigated in surgically treated patients with brain tumor-induced temporal lobe epilepsy. Tumors involving the hippocampus were identified as the foci of epilepsy in 13 patients (seven male and six female) and resected after epileptic discharges were found at the hippocampus on intraoperative electrocorticogram. The mean age at operation was 29.8 +/- 11.5 years and the mean age of seizure onset was 19.9 +/- 10.8 years. Because only three of the 13 patients who underwent temporal lobectomy for brain tumors involving the hippocampus had Ammon's horn sclerosis pathologically, it was concluded that it was very unlikely that the Ammon's horn sclerosis was produced by the epileptic seizures. Two of the three patients with pathological signs of Ammon's horn sclerosis had episodes of coma, covulsion, high fever and cyanosis in their past histories that might have portended the appearance of Ammon's horn sclerosis later in their lives.

The medial temporal lobe (MTL) is known to play important roles in learning and memory in both humans and animals. Some investigators have proposed that the rhythmic slow activity (RSA) or theta that can be recorded in an animal hippocampus is related to learning and memory. It is unclear whether the human hippocampus displays a similar activity. In the past few years, we have studied electrophysiological properties of the human medial temporal lobe (MTL) during wake and all-night sleep. In this paper, we will summarize our results in the electrophysiology of the human medial temporal lobe during sleep and wake and discuss their physiological significances. Electrocorticograms (ECoG) during wake, slow wave sleep (SWS) and rapid eye movement (REM) sleep were subjected to fast Fourier transformation (FFT) analysis. During wake, two peaks, beta-1 (10–20 Hz) and gamma (30–150 Hz) were consistently observed across the subjects. In SWS, the beta-1 peak disappeared but gamma remained although slightly reduced. During REM sleep, beta-1 appeared again, but the peak frequency was slightly lower than that during wake. The gamma peak was also present in REM sleep. These results indicate similarities in the human MTL gamma and beta-1 when compared to animal gamma and RSA in the hippocampus. Thus, this suggests the functional significances of these two MTL oscillations in relation to learning and memory throughout wake and sleep. © 2001 Elsevier Science B.V.

We studied the postoperative development of 14 children with cortical dysgenesis who underwent modified functional hemispherectomy (hemispherotomy) at the age of 6 years or younger. At follow-up of 24-72 months (median of 47 months), six (43%) were seizure-free, six achieved > 90% reduction, one achieved 50-90% reduction, and one achieved 0-50% reduction in seizure frequency. At the preoperative and final postoperative examinations, mean scores of developmental quotient (DQ) were as follows: 25.5 and 31.9 in total DQ, 26.0 and 33.7 in intellectual DQ, and 27.4 and 22.9 in motor DQ. Children scoring > 50 points in preoperative intellectual DQ score obtained near-normal intellectual DQ postoperatively, while, those scoring < 10 DQ preoperatively remained at a low developmental level. Among children with DQ scores in the range from 10 to 50. two children who obtained seizure-free outcome and were operated upon in the first 3 years of life achieved marked developmental progress. The present study indicated that high preoperative intellectual DQ and cessation of seizures seem to be associated with better postoperative intellectual development. However, long-term observation of postoperative development and an accumulation of more cases will be needed before we can reach a firm conclusion. (C) 2002 Elsevier Science B.V. All rights reserved.

Global cerebra ischemia models for genetically engineered mice are of particular importance for the study of delayed neuronal death, but have been complicated by variability of vascular anatomy. Here we developed a 5-min cardiac arrest model that was not affected by vascular anatomy, and evaluated the hippocampal neuronal injury in BL/6 and SV129 mice. Despite prolonged anoxic depolarization for approximately 7 min, however, no consistent ischemic neuronal injury was noted in the CA1 sector of the hippocampus in both strains. Thus, our observations suggested that murine hippocampal neurons are relatively resistant to ischemia compared with those in other rodents. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Radiosurgical treatment of intractable epilepsy has emerged as a noninvasive alternative to resection. Although gamma knife surgery (GKS) reportedly is effective when the radiation dose is sufficient to cause a destructive reaction in the targeted medial temporal lobe, the optimal target area and dose distribution are largely unknown. Some investigators have suggested that focused irradiation from a nondestructive dose is also effective. In this article the authors report two cases of medial temporal lobe epilepsy in which the patients underwent GKS performed using a 50% marginal dose of 18 Gy covering the amygdala hippocampal head and body, and parahippocampal gyrus. In both cases this procedure failed to control seizures. Both patients became seizure free after undergoing anterior temporal lobectomy 30 and 16 months, respectively, after radiosurgery.

We report a case of successful radiosurgical treatment of lesional epilepsy of mesial temporal origin. A patient presented with a 2-year history of medically intractable complex partial seizures associated with a mesial temporal angioma. Interictal scalp EEG and MEG showed focal epileptiform activity around the lesion. 99mTc-HMPAO-SPECT and 18F-FDG-PET demonstrated depressed blood flow and glucose metabolism in the corresponding temporal lobe. The patient underwent gamma knife radiosurgery for the causative lesion with a low marginal dose of 18 Gy. After treatment, the partial attack ceased without shrinkage of the lesion or peri-lesional parenchymal radiation injury.

Conflicting findings of the effect of climate on onset of subarachnoid hemorrhage (SAH) may result from the influence of strenuous activities which can trigger aneurysmal rupture independent of climatological factors. The effect of climate and patient activities on onset of SAH were analyzed. The clinical records of 786 consecutive patients with aneurysmal SAH admitted to our hospital for 10 years were reviewed. Activities at onset were categorized according to the intensity of strain at onset. Seasonal variation, circannual cyclic trend, and association with 90 meteorological factors were examined in each category and the results were compared between categories. Bimonthly occurrence in the light strain group showed a significant seasonal variation and cyclic trend with two peaks in early spring and fall, whereas no significant trend was detected in the overall patients and in the heavy strain group. The significant meteorological factors were global solar radiation, sunshine hours, changes in mean and minimum temperature and mean vapor pressure from the previous day, and minimum pressure in the previous 7 days. Lower global solar radiation in the light strain group was associated with onset with the lowest p value (p = 0.0046). No factors were significant in the heavy strain group. There is some evidence of the possible influence of climatological factors on onset of SAH without strenuous activity. Strenuous activity seems to affect onset more strongly, which masks any effect of climate.

Object. The purpose of this study was to present a combinatorial approach used to develop a subarachnoid hemorrhage (SAH) grading scale based on the patient's preoperative Glasgow Coma Scale (GCS) score. Methods. There are 4094 different combinations that can be used to compress the 13 scores of the GCS into two to 12 grades. Break points, the positions in the scale in which two adjacent scores connote a significantly different outcome, are obtained by a direct comparison of the GCS and the Glasgow Outcome Scale (GOS). Guided by the break points, the number of combinations to be considered can be limited. All possible combinations are statistically analyzed with respect to intergrade differences in outcome. Single combinations, with the maximum number of grades having maximum intergrade outcome differences for each corresponding set of adjacent grades, must be selected. The authors verified the validity of this combinatorial approach by retrospectively analyzing 1398 consecutive patients with aneurysmal SAH who underwent surgery within 7 days of the last hemorrhage episode. The patients' GCS scores were assessed just before surgery and their GOS scores were estimated 6 months post-SAH. The combinatorial approach yields only one acceptable grading scale: I (GCS Score 15) II (GCS Scores 11-14) III (GCS Scores 8-10) IV (GCS Scores 4-7) and V (GCS Score 3). Conclusions. The combinatorial approach, guided by the break points, is so simple and systematic that it can be used again in the future when revision of the grading scale becomes necessary after development of new and effective treatment modalities that improve patients' overall outcome.

The effect of propentofylline, an adenosine uptake inhibitor, on ischemic tolerance was investigated in the gerbil global ischemia model. Propentofylline was administered 24 hours after short preconditioning ischemia, and animals were subjected to 5-minute ischemia 24 hours thereafter. Propentofylline at a dose of 20 mg/kg intraperitoneally, but not at a dose of 10 mg/kg, significantly potentiated the protective effect of preconditioning ischemia in the CA1 hippocampal neurons. This effect was completely abolished by simultaneous administration of theophylline (20 mg/kg), an adenosine receptor blocker. This finding suggests the involvement of adenosine receptor for the development of ischemic tolerance.