Recapitulating cortical development with organoid culture in vitro and modeling abnormal spindle-like (ASPM related primary) microcephaly disease

The development of a cerebral organoid culture in vitro offers an opportunity to generate human brain-like organs to investigate mechanisms of human disease that are specific to the neurogenesis of radial glial (RG) and outer radial glial (oRG) cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing neocortex. Modeling neuronal progenitors and the organization that produces mature subcortical neuron subtypes during early stages of development is essential for studying human brain developmental diseases. Several previous efforts have shown to grow neural organoid in culture dishes successfully, however we demonstrate a new paradigm that recapitulates neocortical development process with VZ, OSVZ formation and the lamination organization of cortical layer structure. In addition, using patient-specific induced pluripotent stem cells (iPSCs) with dysfunction of the Aspm gene from a primary microcephaly patient, we demonstrate neurogenesis defects result in defective neuronal activity in patient organoids, suggesting a new strategy to study human developmental diseases in central nerve system.

Human prefrontal layer II interneurons in areas 46, 10 and 24 / Interneuronas de la lámina II en las áreas prefrontales 46, 10 y 24 del humano

Background: Prefrontal cortex (PFC) represents the highest level of integration and control of psychic and behavioral states. Several dysfunctions such as autism, hyperactivity disorders, depression, and schizophrenia have been related with alterations in the prefrontal cortex (PFC). Among the cortical layers of the PFC, layer II shows a particular vertical pattern of organization, the highest cell density and the biggest non-pyramidal/pyramidal neuronal ratio. We currently characterized the layer II cytoarchitecture in human areas 10, 24, and 46. Objective: We focused particularly on the inhibitory neurons taking into account that these cells are involved in sustained firing (SF) after stimuli disappearance. Methods: Postmortem samples from five subjects who died by causes different to central nervous system diseases were studied. Immunohistochemistry for the neuronal markers, NeuN, parvalbumin (PV), calbindin (CB), and calretinin (CR) were used. NeuN targeted the total neuronal population while the rest of the markers specifically the interneurons. Results: Cell density and soma size were statically different between areas 10, 46, 24 when using NeuN. Layer II of area 46 showed the highest cell density. Regarding interneurons, PV+-cells of area 46 showed the highest density and size, in accordance to the proposal of a dual origin of the cerebral cortex. Interhemispheric asymmetries were not identified between homologue areas. Conclusion: First, our findings suggest that layer II of area 46 exhibits the most powerful inhibitory system compared to the other prefrontal areas analyzed. This feature is not only characteristic of the PFC but also supports a particular role of layer II of area 46 in SF. Additionally, known functional asymmetries between hemispheres might not be supported by morphological asymmetries.

Antecedentes: La corteza prefrontal (CPF) representa el nivel más alto de integración y control de funciones psíquicas y comportamentales. Varias patologías como autismo, desórdenes de hiperactividad, depresión y esquizofrenia se han relacionado con alteraciones de la CPF. La lámina II de las áreas que constituyen la CPF posee un patrón de organización vertical, una alta densidad celular y la mayor proporción de neuronas no-piramidal/piramidal. Sin embargo, la distribución del componente inhibitorio en estas regiones no se ha descrito. Objetivo: En el presente estudio nos propusimos caracterizar la lámina II de las áreas 10, 24 y 46 del humano, particularmente su componente inhibitorio teniendo en mente su participación en procesos de actividad sostenida relevantes cuando desaparece el estímulo. Métodos: Se utilizaron muestras de cinco sujetos que fallecieron por causas diferentes a enfermedades del sistema nervioso. Se tomaron secciones de las áreas 10, 24 y 46 de Brodmann y se procesaron con los anticuerpos contra NeuN para determinar la población neuronal total y contra Parvalbumina (PV), Calbindina (CB) y Calretinina (CR) para analizar la población de interneuronas. Resultados: Los resultados no mostraron diferencias interhemisféricas entre las áreas. Sin embargo, las tres áreas seleccionadas son significativamente diferentes entre sí en todos los parámetros analizados. El área 46 posee la mayor densidad y tamaño de interneuronas positivas para PV. Conclusiones: La ausencia de asimetrías morfológicas no permite explicar las asimetrías funcionales. La lámina II del área 46 posee el sistema inhibitorio más poderoso. Teniendo en cuenta la arquitectura modular de las capas supragranulares, este sistema inhibitorio subyace a la actividad sostenida, eje fundamental de la memoria operativa.

Proton magnetic spectroscopy agreed better with magnetic resonance image to lateralization of epileptogenic zone than with surface electroencephalography / Espectroscopia de protons de hidrogenio na investigacao ambulatorial das epilepsias extra-temporais

Objective To analyze the agreement rate of proton magnetic spectroscopy with magnetic resonance image (MRI) and surface electroence-phalography (EEG) in extratemporal neocortical epilepsies. Methods A cross-sectional study, type series of cases included 33 patients, age range 13–59 years old, of both gender, presenting structural alteration identified by MRI (75.8%) or by neurophysiologic techniques (72.7%). The variables were alterations of N-acetyl-aspartate/choline, N-acetyl-aspartate/creatine, choline/creatine, and N-acetyl-aspartate/cho-line+creatine coefficient of asymmetry. Results Agreement rates of lateralization by coefficient of asymmetry of NAA/Cho, NAA/Cr, Co/Cr, and NAA/Cho+Cr with MRI, independent of alteration of surface EEG, were equal to 93.3, 57.9, 15.4, and 93.3%, respectively, modifying to 100, 33.3, 0, and 100%, in 16 patients, with lateralization agreement of MRI and surface EEG. Conclusion Proton magnetic spectroscopy agreed better with MRI to lateralization of epileptogenic zone than with surface EEG. .

Objetivo Analisar a taxa de concordância da espectroscopia de prótons de hidrogênio com imagem de ressonância magnética (IRM) e o eletrencefalograma (EEG) de superfície nas epilepsias neocorticais extratemporais. Métodos Estudo transversal, série de casos, incluiu 33 pacientes, com idade de 13 a 59 anos, de ambos os gêneros, apresentando alteração estrutural à IRM (75,8%) ou neurofisiológica à (72,7%). As variáveis estudadas foram as alterações dos coeficientes de assimetria de N-acetil-aspartato/colina, N-acetil-aspartato/crea-tina, Colina/Creatina e N-acetil-aspartato/colina+creatina. Resultados As taxas de concordância de lateralização dos coeficientes de assimetria de NAA/Co, NAA/Cr, Co/Cr e NAA/Co+Cr com a IRM, independentemente de alterações do EGG de superfície, passaram de 93,3, 57,9, 15,4, 93,3%, respectivamente, para 100, 33,3, zero, 100%, em 16 pacientes, mostrando concordância de lateralização entre IRM e EEG de superfície. Conclusão A espectroscopia de prótons de hidrogênio concordou melhor com a lateralização da zona epileptogênica pela IRM do que com o EEG de superfície. .

Diagnostic methods for extra-temporal neocortical focal epilepsies: present and future / Métodos diagnósticos das epilepsias focais neocorticais extratemporais: presente e futuro

The progress of epilepsies diagnosis has been great, but, amongst the diagnostic detailing that demand research, one of the most important is the essential lateralization and localization of epileptogenic zone, considered as the cerebral cortex region, that removed, will result in a free state of seizures. The present study aims to analyze the possible uses of proton spectroscopy for clinical and pre-surgical evaluation of focal extratemporal epilepsies, since this group presents the highest difficulty degree for lateralizing and locating epileptogenic zones. In almost all cases, a non invasive diagnosis can be performed using routine electroencephalography, video-electroencephalography - considered as gold standard, and magnetic resonance imaging. However, when the results of these exams are contradictory, some patients need invasive techniques, as the intra-cranial video-EEG, using deep electrodes, sub-dural strip and grid, that are associated with increased diagnostic cost and risk of complications, as cerebral hemorrhages and intra-cranial infections. Proton spectroscopy appears as a possibility, given its capacity to evaluate cerebral metabolism, by N-acetyl-aspartate (NAA), creatine (Cre) and choline (Cho) concentrations, amongst other metabolites. This non invasive method may provide time reduction of this evaluation and reliable level improvement for this topographical diagnosis.

Tem sido grande o progresso no diagnóstico das epilepsias, mas dentre os detalhamentos diagnósticos a exigir pesquisas, estão a lateralização e a localização precisas da zona epileptogênica, considerada como a região do córtex cerebral que, removida, irá resultar num estado livre de crises. Por meio de revisão da literatura, o objetivo deste estudo é expor e analisar os métodos diagnósticos das epilepsias neocorticais extratemporais, dadas as características que as tornam mais complexas do que as epilepsias temporais visto que estas apresentam o maior grau de dificuldade para lateralização e localização das zonas epileptogênicas. Na maior parte dos casos, o diagnóstico pode ser firmado de forma não invasiva, empregando-se a eletrencefalografia de superfície, a vídeo-eletrencefalografia, considerada o padrão-ouro, e a imagem por ressonância magnética. No entanto, quando os resultados dessas investigações são contraditórios, alguns pacientes necessitam de técnicas invasivas, como o vídeo-EEG intracraniano, utilizando eletrodos profundos, placas ou estrias subdurais, que se associam ao aumento do custo diagnóstico e do risco de complicações, como as hemorragias cerebrais e as infecções intracranianas. A espectroscopia de prótons surge como uma possibilidade, dada sua capacidade de avaliar o metabolismo cerebral, por meio das alterações de N-acetil aspartato (NAA), creatina (Cr) e colina (Co), dentre outros metabólitos. Esse método não invasivo pode reduzir o tempo de avaliação e melhorar o nível de confiança desse diagnóstico topográfico.

Effects of 1 Hz Repetitive Transcranial Magnetic Stimulation on Cortical Excitability and Seizure Reduction in Intractable Neocortical Epilepsy / 대한간질학회지

BACKGROUND & OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) can modulate the excitability of cortical networks, possibly reduce the excitability by low frequency stimulation. In this study, we are conducting a study using 1 Hz rTMS in patients with intractable neocortical epilepsy. We wish to see whether 1Hz rTMS induces considerable changes in the cortical excitability and whether it leads to a significant reduction in seizure frequency in individual patients. METHODS: Patients with intractable neocortical epilepsy were recruited, and 1 Hz rTMS (110% of resting motor threshold, 1800 stimuli twice a day) was delivered to the seizure focus for 5 consecutive days. Resting motor threshold (r-MT), MEP amplitudes at different intensities, intracortical inhibition (ICI) and intracortical facilitation (ICF) were measured as TMS indices for motor cortical excitability. TMS measures were repeated before and after daily rTMS session, and again after 2 weeks. RESULTS: Four patients (aged 15 to 53, 3 females and 1 male, 2 TLE and 2 FLE) were described here:cortical excitability in 2 neocortical TLE patients showed lower r-MT and reduced ICF in ipsilateral hemisphere to epileptic focus. One of them with cortical dysplasia showed increased r-MT and ICI, and decreased ICF after daily rTMS session. This patient was seizure-free for 10 weeks, after which the seizure frequency returned to the baseline. CONCLUSIONS: Our preliminary data shows that 1 Hz rTMS may decrease cortical excitability and/or intracortical facilitation, and increase intracortical inhibition after daily rTMS. These findings suggest possible therapeutic effects of low frequency rTMS for patients with intractable neocortical epilepsy.

Effect of Seizure on Hippocampus in Mesial Temporal Lobe Epilepsy and Neocortical Epilepsy: MR Spectroscopy Study / 대한간질학회지

PURPOSE: This study was performed to evaluate the effect of seizures on the bilateral hippocampus in mesial temporal lobe epilepsy (mTLE) and neocortical epilepsy by single voxel proton magnetic spectroscopy. METHODS: Forty-one patients with mTLE having unilateral hippocampal sclerosis and 43 patients with a neocortical epilepsy who underwent subsequent epilepsy surgery were recruited. Ninety-five percent confidence intervals of N-acetyl aspartate/choline (NAA/Cho) and NAA/creatine (NAA/Cr) ratios in 20 healthy control subjects were used as threshold values to determine abnormal NAA/Cho and NAA/Cr. The relationship between the results of MRS and the duration of epilepsy, the frequency of seizure, the effect of secondary generalized tonic clonic seizures (2GTCS), and the postsurgical outcome was evaluated. RESULTS: NAA/Cho and NAA/Cr were significantly lower in the ipsilateral hippocampus of mTLE and neocortical epilepsy. NAA/Cho was abnormally low in the ipsilateral hippocampus in 43.9% (18/41) and bilateral hippocampus in 26.8% of mTLE patients. Ipsilateral or bilateral abnormal NAA/Cr was detected in 46.3% (19/41) of mTLE. NAA/Cho was abnormally lower in the ipsilateral hippocampus in 27.9% and bilateral hippocampus in 41.9% of neocortical epilepsy patients. Ipsilateral or bilateral abnormal NAA/Cr was detected in 32.6% of the patients with neocortical epilepsy. Using AIs for patients with bilaterally abnormal ratios of NAA/Cho and NAA/Cr combined with unilateral abnormal ratio, the seizure focus was correctly lateralized in 65.9% of the patients with mTLE and 48.8% of neocortical epilepsy patients. Bilateral NAA/Cho abnormality was significantly related with a poor surgical outcome in mTLE. No significant relationship was found between the results of NAA/Cho or NAA/Cr and the surgical outcome in neocortical epilepsy. The mean contralateral NAA/Cr ratio of the hippocampus in mTLE was significantly lower in patients with a history of the secondary generalized tonic clonic seizure (2GTCS) than in those without it. CONCLUSIONS: Our results demonstrate functional abnormality of the hippocampus in neocortical epilepsy and the relation between 2GTCS and NAA/Cr of the contralateral hippocampus in mTLE. This proves the presence of the seizure effect on the hippocampus in neocortical epilepsy as well as in mTLE.

Limited Predictive Ability of Hippocampal Single Voxel MR Spectroscopy in Surgically Proven Epilepsy

OBJECTIVE: The authors evaluate the predictability of single voxel proton magnetic resonance spectroscopy(MRS) for hippocampal abnormalities in medial temporal lobe epilepsy(MTLE), lateral temporal lobe epilepsy(latTLE) and extratemporal lobe epilepsy(extraTLE). METHODS: Twenty healthy volunteers and 42 patients with MTLE, 17 with latTLE and 23 with extraTLE, were examined preoperatively with MRS. The NAA/(Cho+Cr) ratios were calculated from the MRS peaks obtained bilaterally from both hippocampi. RESULTS: The mean NAA/(Cr+Cho) ratios showed a stepwise increase from the ipsilateral hippocampus in the MTLE group to the normal control group. In the 42 MTLE patients, the mean NAA/(Cho+Cr) ratio value for the ipsilateral hippocampus was 0.39. This was 17.3% lower than the 0.489 measured for the contralateral hippocampus (p=0.005). This was also significantly lower when compared with the hippocampi of latTLE and extraTLE patients ipsilateral to the epileptogenic zone and also with the normal control group (p< 0.05). The mean ratio value of the contralateral hippocampi was also significantly lower when compared with the normal control group (p=0.000). The mean ratio value measured on postoperative MRS showed little metabolic recovery in the MTLE (from 0.455 to 0.481, p=0.48) compared to the latTLE (from 0.438 to 0.52, p=0.09). CONCLUSION: The MRS might be inconclusive in determining whether the non-epileptogenic hippocampus is affected by epileptiform discharge propagation from the epileptogenic hippocampus or from the remote epileptogenic zone other than the hippocampus. Therefore, physicians should be cautious when determining whether the contralateral hippocampus in MTLE or both hippocampi in neocortical epilepsy is abnormal and whether they should be resected together with the epileptogenic zone.

Interhemispheric Reorganization of Memory Function Assessed by Wada Test in Patients with Mesial Temporal Lobe Epilepsy

BACKGROUND: We investigate an interhemispheric reorganization of memory functions using Wada test in patients with unilateral mesial temporal lobe epilepsy (MTLE). METHODS: We included 70 patients with unilateral MTLE and 37 with neocortical epilepsy (NE). The Wada memory stimuli were composed of 10 items. Scores for each injection were calculated with 1 and 0.5 points assigned for each correct free recall and recognition, respectively. A cut-off asymmetry score for lateralization of memory deficit was defined as 2 points. We statistically analyzed the proportion of memory asymmetry and the average memory score according to the type of epilepsy and the lateralization of seizure focus. RESULTS: The lateralizations of memory deficit determined by Wada memory asymmetry were evenly distributed in the left MTLE (n=34): left in 12 (36%), right in 11 (32%), and undetermined in 11 (32%). However, most (92%) of the right MTLE (n=36) were correctly lateralized to the side of seizure focus. More than 90% of patients with NE were lateralized to right hemisphere regardless of the seizure laterality. The average total (left plus right) memory score were not significantly different between each group. However, right memory score in left MTLE or left memory score in right MTLE were significantly higher than those in NE. The earlier age at seizure onset and the longer duration of epilepsy were observed in patients with left MTLE who had ipsilateral memory deficit comparing to those who had contralateral memory deficit. CONCLUSIONS: A pure interhemispheric reorganization of memory functions could occur in some patients with MTLE. It may be influenced by age at the onset of a seizure and the duration of epilepsy.

Interhemispheric Reorganization of Memory Function Assessed by Wada Test in Patients with Mesial Temporal Lobe Epilepsy

BACKGROUND: We investigate an interhemispheric reorganization of memory functions using Wada test in patients with unilateral mesial temporal lobe epilepsy (MTLE). METHODS: We included 70 patients with unilateral MTLE and 37 with neocortical epilepsy (NE). The Wada memory stimuli were composed of 10 items. Scores for each injection were calculated with 1 and 0.5 points assigned for each correct free recall and recognition, respectively. A cut-off asymmetry score for lateralization of memory deficit was defined as 2 points. We statistically analyzed the proportion of memory asymmetry and the average memory score according to the type of epilepsy and the lateralization of seizure focus. RESULTS: The lateralizations of memory deficit determined by Wada memory asymmetry were evenly distributed in the left MTLE (n=34): left in 12 (36%), right in 11 (32%), and undetermined in 11 (32%). However, most (92%) of the right MTLE (n=36) were correctly lateralized to the side of seizure focus. More than 90% of patients with NE were lateralized to right hemisphere regardless of the seizure laterality. The average total (left plus right) memory score were not significantly different between each group. However, right memory score in left MTLE or left memory score in right MTLE were significantly higher than those in NE. The earlier age at seizure onset and the longer duration of epilepsy were observed in patients with left MTLE who had ipsilateral memory deficit comparing to those who had contralateral memory deficit. CONCLUSIONS: A pure interhemispheric reorganization of memory functions could occur in some patients with MTLE. It may be influenced by age at the onset of a seizure and the duration of epilepsy.

The Usefulness of 3D-Surface Rendering of the MRI in Surgical Treatment of Patients with Intractable Neocortical Epilepsy

BACKGROUND: This study is designed to indicate the role of 3D-surface rendering of the MRI in defining and resect-ing the epileptogenic zone. METHODS: 25 healthy volunteers and 55 patients were studied. Conventional MRI and 3D-surface rendering were performed. Sulcal and gyral patterns were assesed by a neuroradiologist and a neurologist with-out the clinical informations. Chronic video-EEG monitoring with surface and subdural grid electrodes, and PET were done. Resection was performed based on data of the EEG recordings and 3D-surface rendering. RESULTS: Conventional MRI identified structural abnormality ("MRI-identifiable lesion") in 20 patients. 20 of 35 patients without structural abnormality in conventional MRI revealed abnormal sulcal and gyral patterns in 3D-surface rendering of MRI ("3D-identifiable lesion"). Subdural grid EEGs recorded focal or diffuse ictal EEG onset from the region of "3D-identifiable lesion". Histopathologic findings revealed cortical dysplasia in 48 and neocortical gliosis in seven. Overall surgical out-come, at the average follow up period of 32.5 months, showed class I in 63.6%, class II in 25.5%, and class III in 10.9%. Among 20 patients with "MRI-identifiable lesion", 80% were in class I and 20% were in class II. Among 35 patients without "MRI-identifiable lesion", 54.3% were in class I, 28.6% were class II, and 17.1% were in class III. 80% of 20 patients with "3D-identifiable lesion" showed class I and 20% of 15 patients without "3D-identifiable lesion" showed class I. CONCLUSIONS: Identification of "MRI-identifiable lesion" or "3D-identifiable lesion" was of value in defining the epileptogenic zone. Resection of "MRI-identifiable lesion" or "3D-identifiable lesion", which were epilep-togenic in EEGs, promised a good surgical outcome.

Analysis of Ictal Electrocorticographic Features in Nonlesional Neocortical Epilepsy / 대한간질학회지

BACKGROUND: To characterize the ictal electrocorticographic features in relation to surgical outcome in nonlesional neocortical epilepsy (NE). METHODS: Seventeen patients with intractable NE underwent surgeries after chronic subdural recordings. All patients did not have any lesions on brain MRI, which was confirmed by pathology postoperatively. One hundred and eighty one ictal EEGs recorded from subdural electrodes were analyzed. Surgical outcome was determined by seizure reduction rate, and free or more than 75% reduction was defined as favorable outcome. The mean duration of follow-up was 55+/-8.7 months. RESULTS: Reproducible ictal onset zone (IOZ) in more than a half of seizures (p=0.002), and persistent ictal discharges in IOZ from the onset to the end of seizure were found more frequently in the patients with good outcome (p=0.004). Ictal onset patterns consisting of low voltage fast or high amplitude beta spikes predicted a good surgical outcome while rhythmic sinusoidal activity or rhythmic spike/sharp wave were predictive of poor outcome (p=0.01). The ictal onset rhythm consisted of gamma or beta frequencies was more prevalent in the favorable group (p=0.003). CONCLUSIONS: The presence of stable ictal circuit suggested by the consistent earliest activation in more than 50% of seizures and the active participation of IOZ throughout the attack were valuable prognostic factors in addition to the morphology and frequency of ictal onset rhythm.

Comparison of Intracranial Ictal EEG Patterns between Medial and Lateral Temporal Lobe Epilepsy / 대한간질학회지

BACKGROUND AND OBJECTIVES: Temporal lobe epilepsy is the most common uncontrolled epileptic condition and is increasingly treated with surgery. In the absence of definitive results from noninvasive procedures, patients undergo implantation of intracranial electrodes. Intracranial EEG recordings are more accurate than scalp EEG recordings because of minimal artifact and closer approximation to the area of seizure onset. Intracranial EEG patterns between the medial and the lateral temporal lobe epilepsy were thought to have a little differences. METHODS: The authors compared the morphological pattern of seizure onset area, spread pattern, termination pattern and duration of the intracranial EEG manifestation of spontaneous seizures recorded from combined depth and subdural electrodes in 25 intractable temporal lobe epilepsy patients. RESULTS: Sixteen cases were medial temporal onset, six cases were neocortical onset and three cases were multifocal onset. The morphological onset pattern of medial temporal seizures was more likely to have high frequency rhythmic discharge (>13 Hz) and tended to show repetitive spikes prior to the seizure, whereas neocortical seizures were characterized by slow (4-to 10-Hz) and fast frequencies (>35 Hz), without evidence of repetitive spikes. The mean ictal duration at seizure onset of complex partial seizure of medial onset seizure was 121 seconds and was not different from those of neocortical seizures which were 115 seconds. Neocortical seizures take more time to propagate than medial seizures. Propagation to the opposite side of neocortical onset seizure takes 45.53 seconds, whereas medial temporal onset seizure takes 27.92 seconds. In case of second generalization, neocortical seizures continued longer than medial seizures. Of the medial onset temporal lobe seizures, except the simple partial seizures, the 35.2% of seizures initially spread to ipsilateral neocortex, and the 28.2% of seizures initially spread to the contralateral medial temporal lobe and the 25% of seizures simultaneously propagated to the ipsilateral neocortex and contralateral medial temporal lobe. Among the seizures initiated from the neocortex, 79.3% of seizures initially spread to the ipsilateral medial temporal area, but never initially spread to opposite neocortex. The termination pattern of seizures was divided into three types according to their location. In case of medial temporal lobe seizures, the mean of 31% of seizures was diffusely terminated , 38% of seizures terminated at the onset region and 38% of seizures were elsewhere within onset region. On the other hand, 48.6% of neocortical temporal lobe seizure were terminated at seizure onset region. CONCLUSIONS: The pattern of ictal intracranial EEG provides distinguishable differences between the medial temporal seizure and the neocortical temporal seizure.

The Clinical Usefulness of Ictal Surface EEG in Neocortical Epilepsy

BACKGROUND: Localizable scalp ictal EEG appears to be rare in neocortical epilepsy. However, there have not been many studies based upon a large number of patients. This study aims to identify the characteristic patterns of variable neocortical epilepsies and to evaluate their clinical usefulness in the localization of epileptogenic foci. METHODS: We retrospectively assessed 394 noninvasive ictal recordings from 86 patients who subsequently underwent invasive study and resective surgery. Ictal EEGs were recorded by video-EEG monitoring systems with electrodes placed according to the international 10-20 system including additional anterior temporal electrodes. Ictal recordings were analyzed accord-ing to the localizing accuracy and frequency characteristics. The durations of discrete or regional ictal rhythms were also measured. RESULTS: The percentage of discrete or regional EEGs were respectively 26, 52, 70, and 10% in frontal lobe epilepsy (FLE), lateral temporal lobe epilepsy, occipital lobe epilepsy (OLE), and parietal lobe epilepsy (PLE). The ictal rhythms in the order of frequency were theta, delta, beta, alpha, and rhythmic spike-and-wave. The duration of discrete or regional ictal rhythms were significantly shorter in FLE and PLE than in other epilepsies. Ictal beta activ-ity was the most common rhythm in discrete-patterned EEGs. There were some tendencies of poor lateralization in the presence of structural lesion. Types of seizure were not related with the degree of localization except for simple partial seizure. CONCLUSIONS: Ictal surface EEG was clinically helpful in the localization of epileptogenic foci especially in particular neocortical epileptic syndromes.

Ictal Features Differentiating Mesial from Neocortical Temporal Lobe Epilepsies

BACKGROUND: The differentiation of mesial temporal lobe epilepsy (MTLE) from neocortical temporal lobe epilepsy (NTLE) is important in surgical planning of temporal lobe epilepsy (TLE). We tried to find clinical semiology separating one from the other. METHODS: We reviewed 136 seizures of 28 patients who had epilepsy surgery and good clinical outcome (Engel class I or II). We compared the following clinical features between MTLE and NTLE; the history of febrile convulsion, staring, automatism, head version, contralateral dystonic (CLD) and tonic (CLT) posturing, secondarily generalized tonic-clonic seizure (SGTC) frequency, the duration of partial seizures (excluding SGTC part) and time to SGTC and the type of aura (abdominl aura, vertiginous aura, visual aura, gustatory aura, and psychic aura etc.). RESULTS: Eighteen men and ten women were included. Mean age was 29.1+ 8.8 years (11-45). Abdominal aura (p = 0.04), oroalimentary (p < 0.01) and gestural automatism (p < 0.01), CLD (p < 0.01), and CLT posturing (p < 0.01) were seen significantly more often in MTLE and the duration of partial seizure (excluding SGTC) (p < 0.01) was longer in MTLE than NTLE. In NTLE, head version (p < 0.01) and SGTC (p < 0.01) occurred more frequently and the evolution time to SGTC (p = 0.04) was shorter. Duration of automatism and staring and occurrence of unilateral blinking were not different between two groups. CONCLUSION: Abdominal aura, oroalimentary and gestural automatism, CLD and CLT posturing, longer partial seizure duration were more suggesting MTLE, while rapid generalization, frequent SGTC and head version were seen more often in NTLE.

Outcome of Resective Surgery for Non-lesional Neocortical Temporal Lobe Epilepsy

BACKGROUND: Patients with neocortical temporal lobe epilepsy(NTLE) are reported to have less favorable outcome with anterior temporal lobectomy, and the prognostic factors for patients with non-lesional NTLE are not well defined. METHODS: We analyzed the multiple potential predictors of outcome for 26 consecutive medically intractable non-lesional NTLE patients who have had both extracranial and intracranial EEG monitoring during their presurgical evaluation prior to surgery: age, age at seizure onset, sex, seizure semiology, seizure duration and frequency, an etiology, the site of the surgery, the region of intracranial ictal onset, intracranial amobarbital procedure, neuropsychology test, neuroimaging, multiple subpial transection(MST) and surgical pathology. The average follow up period was 37.0+/-11.1(range 20-60) months. The outcome factors analyzed were compared to two types of outcome group; seizure free group(class I) and persistent seizure group(class II-IV) according to Engel's classification. RESULTS: Seventeen of 26 non-lesional NTLE patients(65.4%) were seizure free during follow up. Intracranial ictal onset confined to anterior temporal region only significantly predicted seizure free(p<0.001). Earlier seizure onset(p=0.08) and resection without MST(p=0.10) tended to be seizure free, but not statistically significant. CONCLUSION: Patients with non-lesional NTLE can be a good candidate for a tailored anterior temporal neocorticectomy with/without MST after intracranial EEG monitoring and functional mapping.

Differential Findings of Ictal EEG Pattern between Mesial and Neocortical Temporal lobe Epilepsies

BACKGROUND: Neocortical temporal lobe epilepsy (NTLE) appears to have different characteristics in clinical and electrophysiological aspects from mesial temporal lobe epilepsy (MTLE). Many semiological studies on TLE have been performed. We investigated ictal EEG patterns to differentiate NTLE from MTLE. METHODS: One hundred twenty nine scalp ictal EEG recordings came from 27 pathologically proven TLE patients were analyzed by 1) frequency of ictal discharge at EEG seizure onset (alpha, beta, theta & delta), 2) distribution patterns of ictal EEG onset (diffuse, lateralized & regionalized), 3) electrode of maximum amplitude at initial regionalized portion of ictal EEG, and 4) mesial to lateral and anterior to posterior amplitude ratio of ictal discharges in temporal electrodes. RESULTS: One hundred seven seizures came from MTLE (23 patients) and twenty-two seizures from NTLE (4 patients). Ictal EEG onset with delta wave was observed more frequently in MTLE (42.7%) than in NTLE (14.3%), but beta wave onset was noted more frequently in NTLE (14.3%) than MTLE (0%). Initial ictal EEG discharges were lateralized on ipsilateral hemisphere in 22.0% of MTLE and in 28.6% of NTLE, regionalized over ipsilateral temporal region in 36.6% and 23.8% respectively, and showed diffuse nonlateralized onset in 41.5% of MTLE and 47.6% of NTLE. Both TLE groups revealed most often their maximum negativity of ictal EEG onset at sphenoidal electrode (MTLE: 59.3%, NTLE: 42.8%). Mesial to lateral amplitude ratio of ictal EEG was significantly larger in MTLE group than NTLE group. The amplitude ratio of anterior to posterior temporal electrodes was greater in NTLE group than in MTLE group. CONCLUSION: Delta frequency of ictal onset EEG is more suggestive of MTLE while beta frequency may suggest NTLE. Initial ictal EEG patterns with their maximum on sphenoidal electrode do not differentiate MTLE from NTLE. NTLE has wide vertical and narrow horizontal electrical field, but MTLE has wide horizontal and narrow vertical electrical field.