Negative motor networks: Electric cortical stimulation and diffusion tensor imaging.

INTRODUCTION: This study investigated the networks of Negative motor areas (NMAs) using electric cortical stimulation and diffusion tensor imaging (DTI). METHODS: Twelve patients with intractable focal epilepsy, in which NMAs were identified by electrical cortical stimulation, were enrolled in this study. Electric stimulation at 50Hz was applied to the electrodes during motor tasks to identify the NMAs. DTI was used to identify the subcortical fibers originating from the NMAs found by electrical stimulation. RESULTS: NMAs were found in lateral frontal areas (premotor area (PM) and precentral gyrus) in all 12 patients, in pre-supplementary motor areas (pre-SMAs) in four patients, and in posterior parietal cortices (PPCs) in four. DTI detected fibers connecting to the ipsilateral PMs, PPCs and temporal regions via U-fibers, superior longitudinal fasciculus (SLF), and arcuate fasciculus (AF) from the lateral frontal NMAs. Pre-SMA-NMAs had connections with ipsilateral PMs and contralateral pre-SMAs via the frontal aslant tract and transcallosal commissural fibers, and PPC-NMAs with ipsilateral PMs via SLF and AF. CONCLUSION: This study found the characteristic cortical network of each NMA, and especially revealed new insight of pre-SMA-NMA and PPC NMA. These NMAs might be associated with different mechanism of negative motor response.

Hemispheric asymmetry of the arcuate fasciculus: a preliminary diffusion tensor tractography study in patients with unilateral language dominance defined by Wada test.

OBJECTIVE: Lateralization of language function is a prominent feature of human brain function, and its underlying structural asymmetry has been recently reported in normal right-handed subjects. By means of diffusion tensor tractography (DTT), we investigated the asymmetry of the language network, namely, the arcuate fasciculus in patients in whom the unilateral language dominance was defined by Wada test. METHODS: DTT was performed in 24 patients with a focal lesion or an epileptic focus outside the C-shaped segment of the arcuate fasciculus. The arcuate fasciculus was reconstructed by placing two regions-of-interest in the deep white matter lateral to the corona radiata. The pathway was then divided into one terminating in the temporal lobe (FT tract) and the other in the parietal lobe (FP tract). The relative number and volume of the FT and FP tracts in each hemisphere were submitted to repeated measure ANOVA separately, with the hemisphere as a within-subject factor and with the side of pathology as a between subject factor. RESULTS: The FT tract showed a significantly larger number and volume in the language dominant hemisphere than in the non-dominant hemisphere, while, for the FP tract, no significant hemispheric difference was observed in the relative number or volume. There was a tendency that the FT tract was less lateralized when the pathology was located in the dominant hemisphere than in the non-dominant hemisphere. CONCLUSION: Dominance of the FT tract in the language dominant hemisphere was demonstrated for the first time in a patient population and implicated a clinical utility of DTT for non-invasive evaluation of language lateralization. Our preliminary study might indicate reorganization of the language network in conjunction with pathology.

Usefulness of MEG magnetometer for spike detection in patients with mesial temporal epileptic focus.

The present study investigated the sensitivity of magnetoencephalography (MEG) for spikes depending on sensor type in patients with mesial temporal epileptic focus. We recorded MEG in 6 patients with mesial temporal epileptic focus using two sensor types (magnetometer and gradiometer) simultaneously. The number of spikes detected and the corresponding equivalent current dipole (ECD) parameters (distance from the coordinated head center (radius), and dipole moment) were evaluated with respect to sensor type. Among 426 MEG 'consensus spikes' determined by 3 reviewers, 378 spikes satisfied the predetermined criteria for source localization. Comparing ECD parameters, spikes detected by magnetometer alone displayed a smaller radius and larger dipole moment than those detected by gradiometer alone. Spikes estimated in the mesial temporal area were more frequently detected by magnetometer alone (38.5%) than by gradiometer alone (11.5%), whereas spikes in the lateral temporal area were detected less by magnetometer alone (3.7%) than by gradiometer alone (53.9%). The present results suggest that a magnetometer is advantageous for spike detection in patients with mesial temporal epileptic focus. This also implies the higher sensitivity of magnetometer for deep sources.

Diffusion tensor fiber tractography for arteriovenous malformations: quantitative analyses to evaluate the corticospinal tract and optic radiation.

BACKGROUND AND PURPOSE: We hypothesized that diffusion tensor fiber tractography would be affected by intracranial arteriovenous malformation (AVM). The purpose of the present study was to evaluate the influence of intracranial AVM on corticospinal tract and optic radiation tractography. MATERIALS AND METHODS: The subject group comprised 34 patients with untreated intracranial AVM. Hemorrhage was present in 13 patients and absent in 21 patients. Perinidal fractional anisotropy (FA) and number of voxels along the reconstructed corticospinal and optic radiation tracts were measured, and left-to-right asymmetry indices (AIs) for those values were quantified. Patients were assigned to 1 of 3 groups: tracts distant from nidus, tracts close to nidus without neurologic symptoms, and tracts close to nidus associated with neurologic symptoms. One-way analysis of variance was used to compare differences in AI between groups. Hemorrhagic and nonhemorrhagic groups were assessed separately. RESULTS: In patients without hemorrhage, AI of optic radiation volume (P<.0001), AI of perinidal FA along corticospinal tract (P=.006), and optic radiation (P=.01) differed significantly between groups. In patients associated with hemorrhage, AI of corticospinal tract volume (P=.01), AI of perinidal FA along corticospinal tract (P=.04), and optic radiation (P=.004) differed significantly between groups. CONCLUSIONS: Corticospinal tract and optic radiation tractography were visualized in patients with AVM. In patients with both hemorrhagic and nonhemorrhagic AVM, the 2 fiber tracts close to the nidus were less visualized in the affected hemisphere than those distant from the nidus. Tracts were less visualized in patients with neurologic symptoms than in asymptomatic patients.

A minimally invasive transsulcal approach to the paracentral inner lesion.

OBJECTIVE: Surgical options to remove lesions located deep in the sulcus at the paracentral area are limited. To minimize therapeutic morbidities, such as cortical injuries before the removal, a transsulcal approach was applied by taking the results of neuroimaging and functional mapping into consideration. METHODS: Four patients with paracentral inner lesions including anaplastic astrocytoma, cortical dysplasia, and cavernous angioma were operated on. All lesions were located deep in the paracentral sulci. According to the outcome of MRI and functional mapping of the cortex over the lesion, the central or the postcentral sulcus was opened toward the lesion. Immediately after complete dissection of the sulcus to remove the lesion, neurological findings were evaluated in the awake state. RESULTS: All lesions were situated beneath the hand or foot area. The transsulcal approach was successfully conducted without any neurological deficits in all cases. CONCLUSION: Microsurgical techniques based on anatomic and functional information allow surgeons to reach the lesions deep in the paracentral area safely.

Evaluation of adverse effects in intracarotid propofol injection for Wada test.

The authors evaluated adverse effects of intracarotid propofol injection during a Wada test and their risk factors in 58 patients. Nineteen patients had an adverse effect, mostly in patients receiving more than 10 mg. For patients older than age 55 years or those requiring an injection dose greater than 20 mg to produce hemiplegia, propofol should be injected slowly and patients monitored for excitatory movements.

Radical resection for intrinsic midbrain pilocytic astrocytoma: report of two cases.

BACKGROUND: Intrinsic midbrain glioma has been one of the most challenging therapeutic tasks in neurosurgery due to its prognosis and risks associated with surgical procedures. It is known that the prognosis of pilocytic astrocytoma is relatively good if radical resection can be achieved without severe complications. In order to remove pilocytic astrocytoma within the midbrain radically, we used microsurgical techniques. METHOD: Two patients with intrinsic pilocytic astrocytomas located at the midbrain were operated on. The subtemporal approach was used with a point of entry on the lateral surface of the midbrain just behind the cerebral peduncle. Major vessels were preserved, followed by resection of the intrinsic tumor making the cleavage between tumour and midbrain. FINDINGS: In both patients, intrinsic pilocytic astrocytoma was grossly totally removed with minimal permanent morbidity. They have been able to maintain independent activities in their daily lives without tumor recurrance. CONCLUSIONS: Surgical cure can be accomplished in some cases of midbrain pilocytic astrocytoma, even if the lesions are intrinsic to the midbrain. To remove the tumor totally without further neurological deficits, it is necessary to select a safe access or entrance point to the tumor, and to demarcate the gliotic plane between tumour and midbrain. A long-term follow up with a larger number of patients is needed to establish the significance of radical resection for intrinsic midbrain pilocytic astrocytoma.

Surgical treatment of seizures from the peri-Sylvian area by perinatal insult: a case report of ictal hypersalivation.

UNLABELLED: OBJECTIVES AND IMPORTANCE: It is important to evaluate the seizure manifestation of epilepsy before surgical planning. A patient with partial epilepsy manifesting hypersalivation who underwent resection of the epileptogenic foci with satisfactory postoperative seizure control is reported. CLINICAL PRESENTATION AND INTERVENTION: A 26-year-old man, with a history of perinatal asphyxia, started having medically intractable partial epilepsy at the age of 10 years. His seizure was characterized by throat discomfort followed by hypersalivation. Brain MRI showed an atrophic lesion around the peri-Sylvian area. Scalp recorded EEG did not demonstrate robust epileptiform activity localized enough to define the epileptogenic zone. The patient underwent invasive recording by multiple subdural electrode grids, which showed that the seizure arose from the left anterior frontal operculum. After resection of epileptogenic opercular cortex, the seizures disappeared with no additional neurological deficits. CONCLUSION: Although the responsible sites for ictal drooling are distributed in multiple areas including insula, medial temporal area and operculum, the seizure can be successfully controlled by focus resection of the frontal opercular area in a selected patient with careful presurgical evaluation.

Subregions of human MT complex revealed by comparative MEG and direct electrocorticographic recordings.

OBJECTIVE: To locate the visual motion complex (MT+) and study its response properties in an epilepsy surgery patient. METHODS: A 17-year-old epilepsy patient underwent invasive monitoring with subdural electrodes in the right temporo-parieto-occipital area. MT+ was investigated by cortical electric stimulation and by epicortical visual evoked potentials time-locked to motion onset of sinusoidal gratings (motion VEP). Motion-related visual evoked magnetic field (motion VEF) was also recorded before the electrode implantation to complement the invasive recording. RESULTS: Motion VEPs revealed two subregions within MT+, generating early and late potentials respectively. The early activity with a peak around 130 ms was localized at a single electrode situated immediately caudal to the initial portion of the ascending limb of the superior temporal sulcus (AL-STS). The late activity, peaking at 242-274 ms, was located ventro-rostrally over three electrodes. Among the four electrodes with motion VEPs, cortical stimulation at the most caudal pair elicited motion-in-depth perception involving the whole visual field. In addition to two subregions revealed on the gyral crown, magnetoencephalography (MEG) demonstrated another subregion with a late motion VEF in AL-STS immediately rostral to the electrode with the early motion VEP. CONCLUSIONS: In combination with MEG recording, the present invasive exploration demonstrated human MT+ in a focal area of the temporo-parieto-occipital junction and delineated possible three subregions as indicated by the different latencies and distributions of the motion VEP/VEFs. SIGNIFICANCE: Comparative MEG and direct electrocorticographic recordings delineated possible subregions within the human MT complex.

Intracarotid propofol test for speech and memory dominance in man.

OBJECTIVE: To evaluate the usefulness of propofol as an alternative drug to amobarbital for the Wada test. METHODS: The authors analyzed 67 right-handed patients out of 123 patients who were candidates for neurosurgical therapy and thus underwent the Wada test as a preoperative evaluation. Twelve were tested with propofol and 55 were tested with amobarbital. Test conditions of the Wada test, recovery time of muscle power to manual muscle testing (MMT) Grade 3 (T3/5) and Grade 5 (T5/5), onset time of the first verbal response (Tverb) after injection and that of the first nonverbal response (Tnon-verb), were compared between the two groups. Power spectrum analysis of EEG background activity during the Wada test was performed and the time and spatial distribution of polymorphic slow activities were also compared in three cases. RESULTS: With propofol injection, lateralities of language and memory function were identified in 12 and 9 of 12 patients in comparison to amobarbital (52 and 41 of 55 patients detection in language and memory function). No complications with direct intracarotid injection of propofol were observed. T3/5 and T5/5 with propofol injection were shorter while Tverb and Tnon-verb were longer compared to amobarbital. Absolute power of polymorphic slow EEG waves gradually increased and then rapidly decreased with propofol, which was in contrast to amobarbital injection. CONCLUSIONS: With direct intracarotid propofol injection, the Wada test was satisfactorily performed in all 12 patients and 2 more patients with left-handedness or with different injection dose for each side without any complications. Clinical usefulness of propofol as an alternative drug to amobarbital for the Wada test was indicated.

Seizures arising from the inferior parietal lobule can show ictal semiology of the second sensory seizure (SII seizure).

A 52-year-old right handed man presented with medically intractable partial seizures consisting of numbness on the left upper back spreading to the left upper as well as lower limbs. Head computed tomography and magnetic resonance imaging showed a round calcified lesion in the depth of the superior ramus of the right sylvian fissure. Ictal electrocorticographic recording with chronically implanted subdural electrodes showed low voltage fast activities starting exclusively from an electrode located on the right inferior parietal lobule. No apparent ictal activities were observed from the depth electrodes inserted in the parietal operculum. Somatosensory evoked potentials of 75 ms to 145 ms latency were recorded from the ictal onset zone, which was 2 cm caudal to the perisylvian area corresponding to the second somatosensory area. Seizures arising from the inferior parietal lobule including the angular and supuramarginal gyri can produce partial seizures whose ictal semiology and scalp electroencephalography are indistinguishable from the ones originating from the second somatosensory area.

Use of cavernous sinus EEG in the detection of seizure onset and spread in mesial temporal lobe epilepsy.

PURPOSE: The study goal was to evaluate the clinical usefulness of intravenous EEG recording by placing wire electrodes in the cavernous sinus (CS) and the superior petrosal sinus (SPS) in patients with intractable temporal lobe epilepsy (TLE), with special emphasis on the ictal recording. METHODS: We placed Seeker Lite-10 guide wire as electrodes in the bilateral CS, SPS, or both to simultaneously record both ictal and interictal EEGs with the scalp EEG in five patients with TLE. In addition, in one patient, we averaged interictal scalp and intravascular EEG time-locked to the epileptiform discharge recorded from the CS/SPS-EEG to further delineate the relationship of the spikes between scalp and intravenous recording. RESULTS: In four of five patients, clinically useful recording was obtained to determine ictal focus. We recorded habitual seizures in three patients, and the detailed characteristics of ictal epileptiform discharges were shown. The averaged waveform of interictal epileptiform discharges clarified the spike distribution in the scalp EEGs, which was otherwise undetectable in the single trace. All of the patients completed the intravenous EEG monitoring without any neurological or psychological problems. CONCLUSIONS: The CS/SPS-EEG is a relatively noninvasive method that is useful for the detection of ictal focus and its spreading pattern and thus for the selection of surgical candidate among patients with intractable TLE. Although the number of seizures detected during the short monitoring period may be limited, due to the advantages of its safety and simplicity, it is worth trying for potential surgical candidates before more invasive examinations are applied. A further study with a larger number of patients is needed to estimate its practical risk.

Brain plasticity and cellular mechanisms of epileptogenesis in human and experimental cortical dysplasia.

PURPOSE: The cellular mechanisms that may contribute to epilepsy in resected human cortical dysplasia (CD) were compared with the in utero radiated rat CD model. In human and rat focal hippocampal epilepsy, postsynaptic N-methyl-D-aspartate receptors are up-regulated and presynaptic axon collaterals hyperinnervate them. We hypothesized that in both human and rat CD: (a) the N-methyl-D-aspartate receptor subunits NR1 and NR2A/B would be increased and coassembled, and (b) aberrant axons would be in regions of CD. METHODS: Tests for presynaptic and postsynaptic changes in human and rat CD included the following: (a) cytology, (b) immunocytochemistry, (c) coimmunoprecipitation, (d) double-labeled immunofluorescence, and (e) Timm histochemistry of hippocampal mossy fibers. Within-patient comparisons were made between epileptic tissue, identified by subdural electro-encephalographic seizure onsets, and nonepileptic tissue remote from the focus but within the therapeutic resection. Rats were radiated at embryonic day 17, and offspring were studied postnatally. Statistical comparisons were made against normal rats matched for age and tissue processing. RESULTS: In focal CD patients, NR2A/B subunits and their coassemblies with NR1 were increased significantly more than for the remote nonepileptic cortex. Confocal microscopy showed that NR1-NR2A/B colabeled single dysplastic neurons in both human and rat. In CD rats, mossy fibers innervated the anomalously oriented hippocampal neurons. CONCLUSIONS: Human epileptic CD exhibits a spectrum of abnormal cell orientations and laminations that must require plastic axodendritic changes during development. These altered circuits and receptors could account for the seizures and cognitive deficits found in patients with CD. The radiated rat CD model with cortical dyslaminations and NR2A/B subunit increases would allow the development and testing of drugs targeted at only the NR2A/B subunit or at decoupling the NR1-NR2 coassembly, which could provide a specific antiepileptic drug for dysplastic circuits without inducing general depression of all brain neurons.

Increase of intestinal calcium absorption and bone mineral density by heated algal ingredient (HAI) in rats.

Active absorbable calcium (AAACa) produced by adding HAI (heated algal ingredient) to oyster shell calcium (AACa) is quite efficiently absorbed from the intestine and can increase bone mineral density in elderly osteoporotic patients. HAI was produced by heating the seaweed Cystophyllum fusiforme under reduced pressure, extracting with 6N HCL, and partially neutralizing it. Butanol-ethanol extraction then yielded active HAI fraction A, corresponding to about 1% in weight. The active HAI fraction increased intestinal Ca absorption as shown by a dose-dependent increase of plasma Ca in young male parathyroidectomized rats maintained on a low-Ca diet by administration through a stomach tube with a constant dose of AACa. The action of the active fraction A to maintain bone mass was then tested in young male rats kept on a low-Ca diet for 2 weeks. Bone weight, trabecular bone density, and strength-strain index as indices of bone strength measured by peripheral computed tomography (pQCT) tended to increase when the active HAI fraction was given along with Ca. HAI increased intestinal Ca absorption and prevented the decrease of bone density in rats kept on a low-Ca diet.

NMDAR1 receptor proteins and mossy fibers in the fascia dentata during rat kainate hippocampal epileptogenesis.

We examined the time course of NMDAR1 (NR1) immunoreactivity (IR) in the rat inner molecular layer of the dentate gyrus following unilateral intrahippocampal (hilar) kainic acid (KA) lesions and compared them to progressive aberrant mossy fiber (MF) sprouting into the inner molecular layer (IML). The results demonstrated that NR1 receptors in the IML of the KA side were decreased as early as 3 days after KA-induced denervation, then significantly increased at postinjection day (PID) 7. The densities of NR1 IR in the IML continued to increase up to 5 months. By comparison, MF sprouting did not occur significantly in the IML until PID 17, 10 days after NR1 IR was significantly increased. Recurrent MF-IML neoinnervation significantly increased on days 17, 60, and 150. This progressive MF innervation was significantly correlated with NR1 increases. These results suggest that NR1 receptors were decreased soon after KA-induced deafferentation of granule cell dendrites in the IML; however, they were replaced by new NR1 receptors at increased densities in the granule cell dendrites, which may have released neurotrophic factors to stimulate growth cones of MFs to reinnervate the IML. The progressive increases of NR1 and MFs in the IML suggest that such neosynaptogenesis would contribute monosynaptic recurrent excitatory mechanisms for focal hippocampal hyperexcitability and seizure onsets.

NMDA-receptors 1 and 2A/B coassembly increased in human epileptic focal cortical dysplasia.

PURPOSE: This study was designed to quantify the relation between expressions of NMDA receptor (NMDAR) subunits (1 and 2A/B) and the epileptogenicity in human focal cortical dysplasia. METHODS: Immunoblotting and immunoprecipitation were used to quantify these receptor subunits in tissue resected from EEG-verified epileptic and distal nonepileptic frontal cortical areas in each of three patients as determined by chronic subdural electrode recordings. In each patient, adjacent sections were immunostained to verify that the numbers of dysplastic neurons were greater in epileptic than in nonepileptic cortex. RESULTS: In all patients, NMDAR2A/B expressions and their coassemblies with NMDAR1 were increased in epileptic dysplastic cortex compared with the relatively normal appearing nonepileptic cortex. For all three patients, there were no significant differences in NMDAR1 protein expressions between the two EEG groups. CONCLUSIONS: These results suggest that increased NMDAR1-NMDAR2A/B coassembly contributes to hyperexcitability in dysplastic cortical neurons and focal seizure onsets.

Selective coexpression of NMDAR2A/B and NMDAR1 subunit proteins in dysplastic neurons of human epileptic cortex.

NR1 and NR2 are the two gene families for the NMDA receptor. In vitro studies show that while NR2 alone is nonfunctional, NR1 alone produces weak currents to glutamate or NMDA. We previously showed by immunocytochemistry (ICC) that in normal appearing, nonepileptic human cortical neurons, only NR1 and not NR2 proteins were expressed, in contrast to the presence of both NR1 and NR2 in normal rat cortical neurons. We also showed, in dysplastic epileptic cortex, that both NR1 and NR2 were highly expressed using ICC on adjacent 30-microm sections. However, the relative coexpressions of NR1 and NR2 proteins in single neurons in single sections of human epileptic cortex were unknown. In this study, we used double-labeled immunofluorescence and confocal microscopy to examine the distribution and coexpression of subunit proteins for NR1 and NR2A/B in both nondysplastic (control comparison) and dysplastic regions of human brain resected for the treatment of intractable epilepsy (11 patients). In nondysplastic regions, cortical neurons did not have immunoreactivity (ir) for NR2A/B, whereas NR1-ir was abundant. By contrast, dysplastic neurons in the regions with epileptic cortical dysplasia showed intense NR2A/B-ir in the somata and their dendritic processes. These same NR2A/B-ir dysplastic neurons were colabeled by NR1. These results demonstrate directly that dysplastic neurons express both NR2A/B and NR1 proteins, whereas nondysplastic cortical neurons express only NR1 proteins. Selective coexpression of NR2A/B and NR1 in dysplastic neurons suggests that NR2A/B may form heteromeric NR1-NR2 coassemblies and hyperexcitability in dysplastic neurons that could contribute to focal seizure onset.