Source localization and possible causes of interictal epileptic activity in tumor-associated epilepsy

Electrophysiological studies in gliomas have demonstrated action potentials in neoplastic cells. These "spiking tumor cells" are, however, an enigma. In attempt to find evidences for spikes within tumoral borders, 21 patients with different intracerebral tumors were preoperatively screened for the occurrence of epileptogenic discharges using multichannel MEG and EEG. A correlation between histopathology and the distance between dipole and tumor border could be found. Glioma patients showed epileptic activities closer to the border than those with mixed glioneuronal neoplasms and metastases. Four glioma patients demonstrated epileptic activity within the tumor boundary, however, not in the deep center of the tumor. Patch-clamping of cells from acute glioma slices did not yield a correlation between the presence of voltage-gated sodium channels in tumor cells and the MEG/EEG data. Our results demonstrate that the zone with the highest epileptogenic potential is different in gliomas and other brain tumors. However, our data do not strongly suggest that glioma cells are directly involved in the generation of tumor-associated epilepsy in vivo via their capability to generate action potentials.     

Quantitative interictal subdural EEG analyses in children with neocortical epilepsy

PURPOSE: We studied the relation between quantitative interictal subdural EEG data and visually defined ictal subdural EEG findings in children with intractable neocortical epilepsy, and determined whether interictal EEG data are predictive of ictal EEG onset zones. METHODS: Thirteen children (aged 1.2-15.4 years) underwent prolonged intracranial EEG recording, using 48- to 120-channel subdural electrodes. Three distinct 10-min segments of the continuous interictal EEG recording were selected for each patient, and the spike frequency for each channel was determined by using an automatic spike-detection program. Subsequently the average spike frequency of each electrode was compared with ictal assessment (onset, spread, and no early ictal involvement). In addition, 50 distinct interictal spikes were averaged for each patient, and the amplitude and latency after the leading spike (averaged spike showing the earliest peak) were measured for each electrode and analyzed with respect to ictal EEG findings. RESULTS: Reproducibility of the spike-frequency pattern derived from three 10-min segments was high (Kendall's W, 0.85 +/- 0.08). Electrodes showing the highest spike frequency, the highest spike amplitude, and the leading spike were found to be a part of the seizure onset in 13 of 13, 12 of 13, and 10 of 13 cases, respectively. There was significant correlation between ictal assessment and spike frequency as well as spike amplitude. A receiver operating characteristics analysis showed that a cutoff threshold at 14% of the maximal spike frequency resulted in a specificity of 0.90 and a sensitivity of 0.77 for the detection of seizure-onset electrodes. CONCLUSIONS: Quantitative interictal subdural EEG may predict ictal-onset zones in children with intractable neocortical epilepsy.     

脑磁图对非病灶性新皮质癫痫术前评估的价值

目的 研究非病灶性新皮质癫痫发作间期脑磁图(MEG)与手术切除范围一致性与预后的关系.方法 25例非病灶性新皮质癫痫,术前行发作间期MEG检测以及颅内视频脑电监测(i-VEEG),术后随访1年以上并运用Engel法评价预后.结果 术后总体无发作率(Engel IA) 36％ (9/25)、有效率(Engel Ⅰ级、Ⅱ级)68％(17/25).14例MEG与手术切除范围一致组术后8例无发作,无发作率57％(8/14),有效率71％ (10/14);11例不一致组,术后无发作率9％(1/11),有效率64％(7/11),一致组术后无发作率优于不一致组(P＜0.05).结论 非病灶性新皮质癫痫发作间期MEG与手术切除范围一致与术后无发作率有明确相关性.     

Presurgical epilepsy localization with interictal cerebral dysfunction

Localization of interictal cerebral dysfunction with 2-[(18)F]fluoro-2-D-deoxyglucose (FDG) positron emission tomography (PET) and neuropsychological examination usefully supplements electroencephalography (EEG) and brain magnetic resonance imaging (MRI) in planning epilepsy surgery. In MRI-negative mesial temporal lobe epilepsy, correlation of temporal lobe hypometabolism with extracranial ictal EEG can support resection without prior intracranial EEG monitoring. In refractory localization-related epilepsies, hypometabolic sites may supplement other data in hypothesizing likely ictal onset zones in order to intracranial electrodes for ictal recording. Prognostication of postoperative seizure freedom with FDG PET appears to have greater positive than negative predictive value. Neuropsychological evaluation is critical to evaluating the potential benefit of epilepsy surgery. Cortical deficits measured with neuropsychometry are limited in lateralizing and localizing value for determination of ictal onset sites, however. Left temporal resection risks iatrogenic verbal memory deficits and dysnomia, and neuropsychological findings are useful in predicting those at greatest risk. Prognostication of cognitive risks with resection at other sites is less satisfactory.     

Surgical implications of neuromagnetic spike localization in temporal lobe epilepsy

PURPOSE: To investigate the clinical usefulness of magnetoencephalography (MEG) as a guide to the surgical treatment of temporal lobe epilepsy (TLE). METHODS: Preoperative spike localization by MEG was compared with seizure outcome and postoperative spike localization at 12 months after resective surgery in 16 patients with TLE. Spike localization was classified into anterior temporal (AT) and non-AT localization in 11 patients without neocortical lesion treated with anterior temporal lobectomy (ATL); and lesion and lobar localization in five patients with neocortical lesion treated with lesionectomy (n = 3) or lesionectomy with medial temporal resection (n = 2). RESULTS: All five patients with AT localization became seizure free and spike free after surgery. Among the six patients with non-AT localization, two became seizure free and spike free, two became seizure free with residual spikes, one had residual seizures but no spikes, and one had both residual seizures and spikes. All three patients with lesion localization and two with lobar localization had favorable seizure outcome and became spike free after surgery. CONCLUSIONS: MEG spike localization can identify neocortical sources remote from the presumed epileptogenic area. Favorable seizure outcome can be expected in patients with AT localization after ATL and patients with lesion localization after lesionectomy. In contrast, non-AT localization indicates either nonmedial TLE or spike propagation to the posterior and extratemporal neocortex. Similarly, lobar localization indicates spike propagation from an epileptogenic lesion or extensive epileptogenicity. Patients with non-AT localization or lobar localization should undergo intensive evaluations, such as intracranial EEG, for improved seizure outcome.     

Ictal and interictal ECD-SPECT for focus localization in epilepsy

Forty-one ECD (Technetium-99m-ethyl cysteinate dimer) SPECT investigations were undertaken in the course of a presurgical diagnostic work-up in 23 patients with pharmacoresistant focal epilepsy. In 21 patients, both an ictal and interictal SPECT were conducted. In the patients receiving ictal SPECT the tracer was injected between 7 and 30 s after the seizure onset. Of the interictal SPECTs 17 of 23 showed focal hypoperfusion which was consistent in 17 cases (74%) with the area of the electrophysiological focus (EF) and 6 patients had a normal interictal SPECT. Of the ictal SPECTs 18 of 21 (86%) showed regional hyperperfusion, 18 of them in the same location as the EF. Ictal SPECT showed a hypoperfusion similar to that in interictal SPECT in another 3 patients. In these cases seizure duration was short (28–54 s), so that the tracer reached the brain postictally. Our results show that ictal ECD-SPECT is an effective method for demonstrating an epileptogenic focus. Possible reasons for false-negative ictal SPECT results are discussed.     

Ictal SPECT and interictal PET in the localization of occipital lobe epilepsy

PURPOSE: To compare the localizing value of ictal single photon emission computed tomography (SPECT) and interictal fluorodeoxyglucose-positron emission tomography (FDG-PET) in refractory occipital lobe epilepsy. METHODS: Six patients who underwent surgery for refractory epilepsy associated with pathology in the occipital lobe were retrospectively selected from records of the Austin & Repatriation Centre Comprehensive Epilepsy Programme. Interictal SPECT and PET and ictal SPECT were obtained by standard methods. All studies were read by a nuclear medicine expert blinded to clinical data except the diagnosis of epilepsy. RESULTS: Ictal SPECT showed unilateral occipital hyperperfusion in five of six cases often accompanied by temporal lobe hyperperfusion. These patterns were seen in cases with or without magnetic resonance imaging (MRI) abnormality. Interictal SPECT was not localizing in any case, in contrast to PET, which showed occipital hypometabolism in three of five studies. CONCLUSIONS: Ictal SPECT can provide novel localizing data in MRI-negative occipital lobe epilepsy. Interictal PET can provide useful localizing information, but its role in providing novel information was not demonstrated. Interictal SPECT is useful only as a baseline to aid in interpretation of ictal studies.     

Source localization in refractory partial epilepsy.

In this paper, 51 patients with refractory complex partial seizures (CPS) and intracranial structural abnormalities demonstrated with optimum MR (space-occupying: n = 16; atrophic: n = 32; dysplastic: n = 3) were studied. Video-EEG monitoring showed CPS in all patients. In 13 patients, additional intracranial EEG monitoring demonstrated hippocampal seizure onset in 12 and medial occipital ictal onset in 1 patient. Interictal and ictal dipole modeling using a spherical head model and realistic electrode coordinates were performed. Spatiotemporal dipole mapping of interictal epileptic discharges revealed two distinct dipole patterns. Patients with lesions located in the medial temporal lobe (n = 41) and medial occipital lobe (n = 2) uniformly presented a dipole with an elevation of more than 15 degrees relative to the axial plane. Eight out of ten patients with extratemporal lesions and 1 patient with a pure neocortical temporal lesion had a less stable dipole with an elevation less than 15 degrees relative to the axial plane. Dipole modeling of epochs of early ictal discharges revealed a striking correspondence with the interictal findings in individual patients. Ictal dipole modeling identified the ictal onset zone correctly when compared with intracranial EEG recordings from bilateral hippocampal depth electrodes in patients with medial temporal seizure onset. Mapping of dipoles on MR images of individual patients facilitated clinical interpretation of the EEG data. Interictal and ictal dipole mapping provided additional and clinically relevant information and may obviate the need for intracranial EEG studies in some surgical candidates for refractory CPS.     

18F-FDG-PET在颞叶癫痫灶定位中的应用

目的 介绍发作间期 18F-FDG-PET进行颞叶癫痫灶定位的方法,探讨发作间期18F-FDG-PET在颞叶癫痫灶定位中的价值.方法 回顾性分析术前行 18F-FDG-PET检查、手术后随访效果达到 Engle Ⅰ级的82例颞叶癫痫患者的临床资料,对 18F-FDG-PET在颞叶癫痫灶中定位敏感率和特异性进行分析,并与脑电图监测和MRI进行比较.结果 发作间期 18F-FDG-PET检查中癫痫灶表现为低代谢灶,其中68例位于癫痫灶侧颞叶或以颞叶为主合并其它区域,9例位于癫痫灶侧颞叶以外,5例未见低代谢灶.18F-FDG-PET对癫痫灶定位诊断准确率为82.9%(68/82),显著优于MRI和脑电图(P＜0.05),且在MRI阴性和需要埋置电极进行脑电图检查定位的患者中分别有77.4%(41/53)和75%(15/20)可以达到准确的定位癫痫灶.病理阳性者18F-FDG-PET定位准确率显著高于病理阴性者(P＜0.05).结论 18F-FDG-PET定位颞叶癫痫灶具有高敏感性、高特异性的特点,对MRl阴性和需要埋置电极进行检查的颞叶癫痫灶也有良好的定位价值,合理的应用还可能进一步提高结果.     

Dynamic changes of ictal high-frequency oscillations in neocortical epilepsy: using multiple band frequency analysis

PURPOSE: To characterize the spatial and temporal course of ictal high-frequency oscillations (HFOs) recorded by subdural EEG in children with intractable neocortical epilepsy. METHODS: We retrospectively studied nine children (four girls, five boys; 4-17 yr) who presented with intractable extrahippocampal localization-related epilepsy and who underwent extraoperative video subdural EEG (1000 Hz sampling rate) and cortical resection. We performed multiple band frequency analysis (MBFA) to evaluate the frequency, time course, and distribution of ictal HFOs. We compared ictal HFO changes before and after clinical onset and postsurgical seizure outcomes. RESULTS: Seventy-eight of 79 seizures showed HFOs. We observed wide-band HFOs ( approximately 250 Hz, approximately 120 electrodes) in six patients either with partial seizures alone (three patients) or with epileptic spasms (three patients). Three patients with partial seizures that secondarily generalized had wide-band HFOs ( approximately 170 Hz) before clinical onset and sustained narrow-band HFOs (60-164 Hz) with electrodecremental events after clinical onset ( approximately 28 electrodes). In four postoperatively seizure-free patients, more electrodes recorded higher-frequency HFOs inside the resection area than outside before and after clinical seizure onset. In five patients with residual seizures, electrodes recorded more HFOs that were of higher or equal frequency outside the surgical area than inside after clinical onset. CONCLUSION: For partial seizures alone and epileptic spasms, more electrodes recorded only wide-band HFOs; for partial seizures that secondarily generalized, fewer electrodes recorded wide-band HFOs, but in these seizures electrodes also recorded subsequent sustained narrow-band ictal HFOs. Resection of those brain regions having electrodes with ictal, higher HFOs resulted in postsurgical seizure-free outcomes.     

Intracellular currents of interictal penicillin spikes: Evidence from neuromagnetic mapping

To analyze the net intracellular current produced by interictal spikes, we mapped the extracranial magnetic fields of the rat brain following application of penicillin to the right or left medial cingulate cortex. Averaged interictal spikes in both the magnetoencephalogram (MEG) and in the electrocorticogram (ECoG) were composed of 4 temporal components, a biphasic spike and slow wave. Magnetic field maps for each of these components indicated a source at the location of penicillin application, with intracellular currents oriented perpendicular to the surface of the cingulate cortex, along the axis of the major pyramidal cells. The polarity of the magnetic fields for each of the components was reversed between the two cingulate groups, reflecting the respective orientation of pyramidal cells between the juxtaposed faces of the medial cingulate cortex. This neuromagnetic study of net intracellular current complements and extends the analysis of extracellular currents within the penicillin focus obtained using laminar electrodes. These data also demonstrate how animal neuromagnetometry may provide an empirical foundation for the neurogenesis of the MEG and a new unique method for the non-invasive study of population cell physiology.     

Dipole source localization of interictal epileptiform activity in temporal lobe epilepsy with medial temporal lesion

Dipole sources of interictal epileptiform activities recorded by conventional electroencephalogram (EEG) were estimated using the dipole tracing method. Four cases of temporal lobe epilepsy with medial temporal lesions were studied. Two patients with hippocampal sclerosis, one patient with granulation in the hippocampus and one patient with cavernous angioma were involved in the study. Interictal epileptiform activities were classified into two patterns according to the topography of spikes. They were widespread spikes over the parasagittal electrodes (parasagittal spikes) and restricted spikes at the temporal electrodes (temporal spikes). Dipole sources of parasagittal spikes were localized in the medio-basal temporal lobe with vertically orientated vector moment. Dipole sources of temporal spikes were localized in the medio-basal temporal lobe with horizontally orientated vector moment. Locations of dipoles and directions of vector moments were consistent with topography and polarity of spikes. The difference in the two patterns of interictal epileptiform activities was derived from the difference in the direction of the vector moment of dipole sources. There was no difference in the location of dipole sources. Both the dipole sources and the lesions were localized in the same medio-basal temporal lobe. Dipole tracing was very useful in localizing the dipole sources of interictal epileptiform activities and in understanding the neurophysiological background.     

Progressive neocortical damage in epilepsy

Our objective was to determine the pattern and extent of generalized and focal neocortical atrophy that develops in patients with epilepsy and the factors associated with such changes. As part of a prospective, longitudinal follow-up study of 122 patients with chronic epilepsy, 68 newly diagnosed patients, and 90 controls, serial magnetic resonance imaging scans were obtained 3.5 years apart. Image subtraction was used to identify diffuse and focal neocortical change that was quantified with a regional brain atlas and a fully automated segmentation algorithm. New focal or generalized neocortical volume losses were identified in 54% of patients with chronic epilepsy, 39% of newly diagnosed patients and 24% of controls. Patients with chronic epilepsy were significantly more likely to develop neocortical atrophy than control subjects. The increased risk of cerebral atrophy in epilepsy was not related to a history of documented seizures. Risk factors for neocortical atrophy were age and multiple antiepileptic drug exposure. Focal and generalized neocortical atrophy commonly develops in chronic epilepsy. Neocortical changes seen in a quarter of our control group over 3.5 years were likely to reflect physiological changes. Our results show that ongoing cerebral atrophy may be widespread and remote from the putative epileptic focus, possibly reflecting extensive networks and interconnections between cortical regions.     

Topographic movie of ictal high-frequency oscillations on the brain surface using subdural EEG in neocortical epilepsy

PURPOSE: To understand the rapid dynamic changes of ictal intracranial high-frequency oscillations (HFOs) in neocortical epilepsy. METHODS: We integrated multiple band frequency analysis and brain-surface topographic maps of HFOs from ictal subdural EEG (SDEEG) recordings. We used SDEEG to record partial seizures consisting of right-arm jerks with secondary generalization in a 17-year-old right-handed girl. We selected 20-s EEG sections that included preclinical seizure recordings. We averaged the HFO power between 60 and 120 Hz for 25 selected electrodes, made topographic maps from these averaged powers, and superimposed the maps on the brain-surface image. We filmed consecutive HFO maps at a 10-ms frame rate. RESULTS: Before clinical seizure onset, high-power HFOs emerged at the superior portion of the left precentral gyrus, then appeared in the middle of the left postcentral gyrus, and subsequently reverberated between both regions as well as the posterior portion of the left postcentral gyrus. Right-arm extension and facial grimacing started as the HFO power decreased. As generalized tonic-clonic seizures evolved, HFO power increased but remained within the central region. CONCLUSIONS: Topographic movies of intracranial HFOs on the brain surface allow visualization of the dynamic ictal changes in neocortical epilepsy.     

Effect of sleep stage on interictal high-frequency oscillations recorded from depth macroelectrodes in patients with focal epilepsy

Purpose :  To investigate the effect of sleep stage on the properties of high-frequency oscillations (HFOs) recorded from depth macroelectrodes in patients with focal epilepsy.
Methods :  Ten-minute epochs of wakefulness (W), stage 1–2 non-REM (N1-N2), stage 3 non-REM (N3) and REM sleep (R) were identified from stereo-electroencephalography (SEEG) data recorded at 2 kHz in nine patients. Rates of spikes, ripples (>80 Hz), and fast ripples (>250 Hz) were calculated, as were HFO durations, degree of spike–HFO overlap, HFO rates inside and outside of spikes, and inside and outside of the seizure-onset zone (SOZ).
Results :  Ripples were observed in nine patients and fast ripples in eight. Spike rate was highest in N1-N2 in 5 of 9 patients, and in N3 in 4 of 9 patients, whereas ripple rate was highest in N1-N2 in 4 of 9 patients, in N3 in 4 of 9 patients, and in W in 1 of 9 patients. Fast ripple rate was highest in N1-N2 in 4 of 8 patients, and in N3 in 4 of 8 patients. HFO properties changed significantly with sleep stage, although the absolute effects were small. The difference in HFO rates inside and outside of the SOZ was highly significant (p < 0.000001) in all stages except for R and, for fast ripples, only marginally significant (p = 0.018) in W.
Conclusions :  Rates of HFOs recorded from depth macroelectrodes are highest in non-REM sleep. HFO properties were similar in stages N1-N2 and N3, suggesting that accurate sleep staging is not necessary. The spatial specificity of HFO, particularly fast ripples, was affected by sleep stage, suggesting that recordings excluding REM sleep and wakefulness provide a more reliable indicator of the SOZ.     

Predictive variables of interictal psychosis in epilepsy

OBJECTIVE: To evaluate which variables predict interictal psychosis in epilepsy. METHODS: The authors reviewed the biological backgrounds, clinical characteristics, and EEG findings in 246 patients with epilepsy and interictal psychosis and in 658 control patients with epilepsy and no psychotic history. With a logistic regression approach, the significance of each variable for the development of interictal psychosis was evaluated. RESULTS: There are significant differences in family history of psychosis, age at onset of epilepsy, type of epilepsy, lateralization of epileptiform discharges, and level of intelligence between patients with interictal psychosis and those without it. Subsequent logistic regression analysis with all variables demonstrated that family history of psychosis, age at onset of epilepsy, type of seizures, and level of intelligence significantly correlated with psychosis. CONCLUSIONS: A family history of psychosis, earlier age at onset of epilepsy, complex partial seizures or generalized tonic clonic seizures, and borderline intellectual functioning were the most important predictors for development of interictal psychosis.     

Intensive monitoring of interictal psychosis in epilepsy

Ten epileptic patients developed interictal psychosis while being treated in hospital for seizure control. They were subjected to intensive behavioral, video-electroencephalographic, and serum anticonvulsant monitoring for an average of 7.1 weeks in a specialized epilepsy unit. In 9 patients, the interictal psychosis was indistinguishable from acute schizophrenia. Only 5 of these patients had complex partial seizures; the other 4 showed evidence of generalized epilepsies. Thus a “unique” association between schizophreniform psychosis and complex partial seizures, noted by previous authors, could not be confirmed. Only 1 patient showed normalization of the electroencephalogram during psychosis and an inverse relationship between psychosis and seizure frequency. In most cases the emergence of psychosis could not be explained. Interictal psychosis in epilepsy appears to be a spectrum of disorders that may be multifactorially determined.