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Naotaka Usui, Satoshi Maesawa, Yasukazu Kajita, Otone Endo, Shigenori Takebayashi, and Jun Yoshida

Object. Deep brain stimulation (DBS) of subcortical nuclei such as the subthalamic nucleus (STN) or the substantia nigra pars reticulata (SNR) may provide an alternative therapy for intractable epilepsy. The authors attempted to evaluate the antiepileptic effects of DBS to these structures in an experimental seizure model.

Methods. Three groups of rats were prepared. In the first two groups, the rats underwent unilateral implantation of stimulation electrodes in the STN (six rats) or the SNR (six rats). A control group received no electrodes (six rats). Kainic acid (KA) was systemically administered to induce limbic seizures, which started with focal seizures and became generalized secondarily. High-frequency electrical stimulation of the STN or SNR was begun immediately after KA administration, and changes on electroencephalography (EEG) and the magnitude of clinical seizures were evaluated. Results showed that STN stimulation significantly reduced the duration of generalized seizures on EEG, although the total duration of seizures (generalized plus focal seizures) was unchanged. The duration of focal seizures on EEG was prolonged by STN DBS, a result possibly due to the suppression of secondary generalization. In addition, STN DBS reduced the severity of clinical seizures. On the other hand, stimulation of the SNR demonstrated no effect.

Conclusions. Unilateral STN DBS showed significant suppression of the secondary generalization of limbic seizures. Note, however, that SNR DBS was less effective, which implies that in addition to the nigral control of the epilepsy system, another antiepileptic mechanism such as antidromic stimulation of the corticosubthalamic pathway should be considered.

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Satoshi Maesawa, Yoshiki Kaneoke, Yasukazu Kajita, Naotaka Usui, Nobuaki Misawa, Atsuo Nakayama, and Jun Yoshida

Object. The goal of this study was to evaluate the neuroprotective effects conferred by long-term electrical stimulation of the subthalamic nucleus (STN) against degeneration of dopaminergic neurons by assessing motor functional and immunohistological findings in hemiparkinsonian rats.

Methods. In 13 of 25 rats, a concentric microelectrode was stereotactically implanted into the right STN under the guidance of extracellular microelectrode recording. After this had been done the animals were given an injection of 6-hydroxydopamine (6-OHDA) into the right striatum. Seven of the rats received continuous stimulation (frequency 130 Hz, intensity 80–100 µA) for 2 weeks (Group A); the other six did not receive any stimulation during this period (Group B). Twelve rats did not receive electrode implantation and underwent 6-OHDA injection only; these animals served as a control group (Group C). After 2 weeks, motor function in the rats was evaluated by conducting an amphetamine-induced rotation test. Finally, tyrosine hydroxylase—immunoreactive neurons in the pars compacta of the substantia nigra (SNc) were counted to evaluate the extent of degeneration of dopaminergic neurons. Ipsilateral rotation was significantly decreased in Group A, regardless of the effects of stimulation delivered during the test (p < 0.05). Rats in Group B demonstrated typical circling as did those in Group C, except that on stimulation Group B rats immediately stopped circling or changed direction. Tyrosine hydroxylase—immunoreactive neurons in the SNc were significantly preserved in the animals in Group A, whereas neurons in animals in Groups B and C were moderately depleted (p < 0.01).

Conclusions. Acutely, STN stimulation improved rotation symmetry in rats with moderate SNc degeneration. When STN stimulation had been applied for the preceding 2 weeks, motor function was better and SNc neural degeneration was significantly milder. Subthalamic nucleus stimulation thus appears to protect dopaminergic neurons in this hemiparkinsonian model, in addition to improving motor function in these animals.

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Naotaka Usui, Kiyohito Terada, Koichi Baba, Kazumi Matsuda, Takayasu Tottori, Shuichi Umeoka, Tadahiro Mihara, Fumihiro Nakamura, Keiko Usui, and Yushi Inoue

Object

The aim of this study was to investigate the usefulness of a short train of high-frequency (500 Hz) cortical stimulation to delineate the primary motor cortex (MI), supplementary motor area (SMA), primary somatosensory cortex (SI), supplementary sensory area (SSA), negative motor area (NMA), and supplementary negative motor area (SNMA) in patients with epilepsy who were undergoing functional mapping.

Methods

Seventeen patients were studied, all of whom underwent functional mapping using 50-Hz electrical stimulation. After these clinical evaluations, cortical stimulations with a short train of electrical pulses at 500 Hz were performed through subdural electrodes placed at the MI, SMA, SI, SSA, NMA, and SNMA, which had been identified by 50-Hz stimulation, and surrounding cortical areas, while surface electromyography readings were recorded.

Results

Stimulation of the MI elicited motor evoked potentials (MEPs) in contralateral muscles. Stimulation of the SMA also induced MEPs in contralateral muscles but with longer latencies compared with the MI stimulation. Stimulation of the SMA did not elicit MEPs in ipsilateral muscles. Stimulation of the SI, SSA, NMA, and SNMA did not induce MEPs in any muscle. In one patient, MEPs were elicited without seizure induction by 500-Hz stimulation of the electrodes, whereas a 50-Hz stimulation of the same electrodes induced his habitual seizures.

Conclusions

Extraoperative high-frequency stimulation with MEP monitoring is a useful complementary method for cortical mapping without inducing seizure. Stimulation of SMA induces MEPs in contralateral muscles, with longer latencies compared with the stimulation of MI. This finding may be useful for the differentiation between MI and SMA, especially in the foot motor areas.

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Shuichi Umeoka, Kazumi Matsuda, Koichi Baba, Naotaka Usui, Takayasu Tottori, Kiyohito Terada, Keiko Usui, Fumihiro Nakamura, Yushi Inoue, Tateki Fujiwara, and Tadahiro Mihara

Object

To provide greater accuracy in determining the epileptogenic zone during preoperative evaluation, the authors retrospectively examined 123I-iomazenil single-photon emission computed tomography (IMZ SPECT) studies obtained in patients with temporal lobe epilepsy (TLE) in whom there was no evidence of an abnormality on magnetic resonance (MR) images.

Methods

Twelve patients, seven with mesial TLE (MTLE) and five with lateral TLE (LTLE), satisfied the criteria for inclusion in the study. The IMZ SPECT findings in these patients were reviewed retrospectively, and a comparison was made between findings in patients with MTLE and those in patients with LTLE.

Results

The IMZ SPECT studies demonstrated decreased IMZ uptake in the ipsilateral mesial temporal region and the anterobasal temporal lobe in all patients who had MTLE on only one side. On the other hand, IMZ SPECT examinations revealed low IMZ uptake in the ipsilateral lateral temporal lobe in four of five patients with LTLE in whom abnormal findings were restricted to the lateral neocortex. In the remaining patient with LTLE, abnormally low IMZ uptake was found in both mesial and lateral temporal lobes, although pure LTLE was diagnosed by an invasive electroencephalographic evaluation; this patient's habitual seizures continued even after temporal lobectomy, although his mesial structures were spared.

Conclusions

The authors report characteristics of IMZ SPECT findings that differed between patients with MTLE and those with LTLE. The IMZ SPECT examinations proved useful for preoperative evaluation and, to a certain extent, for discrimination between MTLE and LTLE in cases in which MR imaging demonstrated normal findings. The results of this study suggest that IMZ SPECT findings may reflect localization of the epileptogenic zone.

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Hiroshi Hosoyama, Kazumi Matsuda, Tadahiro Mihara, Naotaka Usui, Koichi Baba, Yushi Inoue, Takayasu Tottori, Toshiaki Otsubo, Yumi Kashida, Koji Iida, Hirofumi Hirano, Ryosuke Hanaya, and Kazunori Arita

OBJECTIVE

The aim of this study was to investigate the treatment outcomes and social engagement of patients who had undergone pediatric epilepsy surgery more than 10 years earlier.

METHODS

Between 1983 and 2005, 110 patients younger than 16 years underwent epilepsy surgery at the National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders. The authors sent a questionnaire to 103 patients who had undergone follow-up for more than 10 years after surgery; 85 patients (82.5%) responded. The survey contained 4 categories: seizure outcome, use of antiepileptic drugs, social participation, and general satisfaction with the surgical treatment (resection of the epileptic focus, including 4 hemispherectomies). The mean patient age at the time of surgery was 9.8 ± 4.2 (SD) years, and the mean duration of postoperative follow-up was 15.4 ± 5.0 years. Of the 85 patients, 79 (92.9%) presented with a lesional pathology, such as medial temporal sclerosis, developmental/neoplastic lesions, focal cortical dysplasia, and gliosis in a single lobe.

RESULTS

For 65 of the 85 responders (76.5%), the outcome was recorded as Engel Class I (including 15 [93.8%] of 16 patients with medial temporal sclerosis, 20 [80.0%] of 25 with developmental/neoplastic lesions, and 27 [73.0%] of 37 with focal cortical dysplasia). Of these, 29 (44.6%) were not taking antiepileptic drugs at the time of our survey, 29 (44.6%) held full-time jobs, and 33 of 59 patients (55.9%) eligible to drive had a driver's license. Among 73 patients who reported their degree of satisfaction, 58 (79.5%) were very satisfied with the treatment outcome.

CONCLUSIONS

The seizure outcome in patients who underwent resective surgery in childhood and underwent followup for more than 10 years was good. Of 85 respondents, 65 (76.5%) were classified in Engel Class I. The degree of social engagement was relatively high, and the satisfaction level with the treatment outcome was also high. From the perspective of seizure control and social adaptation, resective surgery yielded longitudinal benefits in children with intractable epilepsy, especially those with a lesional pathology in a single lobe.

Open access

Naoki Ichikawa, Naotaka Usui, Akihiko Kondo, Takayasu Tottori, Tokito Yamaguchi, Hirowo Omatsu, Takayoshi Koike, Hiroko Ikeda, Katsumi Imai, and Yukitoshi Takahashi

BACKGROUND

Surgical treatment of intractable epilepsy caused by porencephaly can be difficult because of poorly localizing or lateralizing electroclinical findings. The authors aimed to determine whether noninvasive evaluations are sufficient in these patients.

OBSERVATIONS

Eleven patients were included in this study. The porencephalic cyst was in the left middle cerebral artery (MCA) area in 9 patients, the left posterior cerebral artery area in 1 patient, and the bilateral MCA area in 1 patient. Interictal electroencephalography (EEG) revealed multiregional, bilateral, interictal epileptiform discharges in 5 of 11 patients. In 6 of 10 patients whose seizures were recorded, the ictal EEG was nonlateralizing. Nine patients underwent ictal single-photon emission computed tomography (SPECT), which revealed lateralized hyperperfusion in 8 of 9 cases. Fluorodeoxyglucose positron emission tomography (FDG-PET) was useful for identifying the functional deficit zone. No patient had intracranial EEG. The procedure performed was hemispherotomy in 7 patients, posterior quadrant disconnection in 3 patients, and occipital disconnection in 1 patient. A favorable seizure outcome was achieved in 10 of 11 patients without the onset of new neurological deficits.

LESSONS

Ictal SPECT was useful for confirming the side of seizure origin when electroclinical findings were inconclusive. Thorough noninvasive evaluations, including FDG-PET and ictal SPECT, enabled curative surgery without intracranial EEG. Seizure and functional outcomes were favorable.

Free access

Yuji Ito, Satoshi Maesawa, Epifanio Bagarinao, Yu Okai, Daisuke Nakatsubo, Hiroyuki Yamamoto, Hiroyuki Kidokoro, Naotaka Usui, Jun Natsume, Minoru Hoshiyama, Toshihiko Wakabayashi, Gen Sobue, and Norio Ozaki

OBJECTIVE

The authors recently reported a novel subsecond analysis method of analyzing EEG–functional MRI (fMRI) to improve the detection rate of epileptic focus. This study aims to validate the utility of this method for presurgical evaluation in pharmacoresistant focal epilepsy.

METHODS

Among 13 patients with focal epilepsy undergoing presurgical examinations including simultaneous EEG-fMRI at 3T, 11 patients had interictal epileptiform discharges (IEDs) during fMRI. The authors used the sequence of topographic maps during the IEDs as a reference to obtain subsecond fMRI activation maps with the same temporal resolution as the EEG data, and constructed “spike-and-slow-wave-activation-summary” (SSWAS) maps that showed the activation frequency of voxels during IEDs. Clusters were defined by thresholding the SSWAS maps (voxel value > 10), and those containing voxels with the top 3 highest activation frequencies were considered significant. Significant hemodynamic responses using conventional event-related (ER) analysis and SSWAS maps were compared with the resection areas and surgical outcomes at 1 year after surgery.

RESULTS

Using ER analysis, 4 (36%) of 11 patients had significant hemodynamic responses. One of 4 patients had significant hemodynamic responses in the resection area and good surgical outcome. Using SSWAS maps, 10 (91%) of 11 patients had significant hemodynamic responses. Six of 10 patients had significant hemodynamic responses in the resection area, and 5 of the 6 patients achieved good surgical outcomes. The remaining 4 patients had significant hemodynamic responses distant from the resection area, and only 1 of the 4 patients achieved good surgical outcomes. The sensitivity, specificity, positive predictive value, and negative predictive value of SSWAS maps were 83.3%, 75.0%, 83.3%, and 75.0%, respectively.

CONCLUSIONS

This study demonstrated the clinical utility of SSWAS maps for presurgical evaluation of pharmacoresistant focal epilepsy. The findings indicated that subsecond EEG-fMRI analysis may help surgeons choose the resection areas that could lead to good surgical outcomes.