Kensuke Kawai

Global Cerebral Ischemia Associated with Cardiac Arrest in the Rat: I. Dynamics of Early Neuronal Changes

Light microscopic neuronal changes were studied in rats subjected to 10 min of global ischemia produced by compression of the major cardiac vessels. Observations of cresyl violet-stained sections revealed early changes involving predominantly GABAergic neurons in various locations. In rats killed 15 min after recirculation, the changes were characterized by the appearance of a clear peripheral zone with condensation of the remaining neuronal cytoplasm. After 1 h, these zones appeared to be compartmentalized into individual pearl-like vacuoles, especially prominent in the nucleus reticularis thalami. After 3 h, the cytoplasmic vacuoles disappeared and the neuronal changes, particularly in the cerebral cortex, striatum, hippocampus, and pars reticulata of the substantia nigra, consisted mainly of hyperchromasia or loss of Nissl substance. After 2 days, the cerebral cortex and thalamus contained occasional neurons with conspicuously large nucleoli. After 7 days, the hippocampus revealed an approximately 50% loss of CA1 pyramidal neurons, associated with intense microglial reactivity in the stratum radiatum, whereas the neuronal destruction was more complete in the nucleus reticularis thalami. Our observations suggest a possibility that early changes in GABAergic neurons may provide a period of neuronal disinhibition and thus contribute to an excitatory ischemic damage in regions connected by GABAergic circuitry.

The motor-evoked potential threshold evaluated by tractography and electrical stimulation

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 approximately 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.

Significance of Simpson grading system in modern meningioma surgery: integration of the grade with MIB-1 labeling index as a key to predict the recurrence of WHO Grade I meningiomas.

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 patients life.

Functional Monitoring for Visual Pathway Using Real-time Visual Evoked Potentials and Optic-radiation Tractography

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.

Expressive and receptive language areas determined by a non-invasive reliable method using functional magnetic resonance imaging and magnetoencephalography

OBJECTIVEIt 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. METHODSWe 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. RESULTSfMRI 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. CONCLUSIONThe 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.

Postoperative development of children after hemispherotomy

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.

Hippocampal transection for treatment of left temporal lobe epilepsy with preservation of verbal memory

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.

Development of Susceptibility to Audiogenic Seizures following Cardiac Arrest Cerebral Ischemia in Rats

Susceptibility to audiogenic seizures (AGS) was investigated in Sprague–Dawley rats subjected to cardiac arrest cerebral ischemia (CACI), produced by compression of the major cardiac vessels. The onset of AGS was regularly observed 1 day after CACI of >5 min duration. The duration of postischemic susceptibility to AGS was directly related to the density of cerebral ischemia, with 50% of more severely ischemic animals still showing AGS susceptibility 8 weeks after CACI. Lesioning of the inferior colliculi (IC) abolished the onset of AGS; no such effect was observed after lesioning the medial geniculate (MG). Glutamic acid decarboxylase (GAD) immunochemistry revealed ∼50% loss of GAD-positive neurons in the IC, which was similar in animals with various durations of AGS susceptibility. Otherwise, there was a conspicuous sprouting of γ-aminobutyric acid (GABA)-ergic terminals in the ventral thalamic nuclei, which peaked ∼1 month after the CACI. Evaluation of GABA-A inhibitory function in the hippocampus by the paired pulse stimulation revealed changes indicating loss of GABA-A inhibition coinciding with the onset of AGS, and its return in animals tested 2 months after CACI. Our observations suggest a potential role of GABA-ergic dysfunction in the postischemic development of AGS.

Usefulness of [11C]methionine PET in the diagnosis of dysembryoplastic neuroepithelial tumor with temporal lobe epilepsy.

Summary:  Purpose: We assessed the diagnostic value of [11C]methionine (MET) positron emission tomography (PET) in the differential diagnosis of dysembryoplastic neuroepithelial tumors (DNETs) among benign tumors associated with temporal lobe epilepsy (TLE).

Theta oscillation in the human anterior cingulate cortex during all-night sleep: An electrocorticographic study

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 patients 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.