OBJECTIVE: To investigate post-operative seizure outcomes, and predictors of surgical outcomes of the malformation of cortical development (MCD) in children with drug-resistant epilepsy (DRE) and age-specific characteristics.
METHODS: We retrospectively analyzed clinical data from 428 children with MCD-related DRE who underwent curative surgical treatment. Statistical analyses were conducted to identify correlative characteristics, prognostic predictors, and differences among various age groups.
RESULTS: After more than 3 years of follow-up, 81.3% of patients achieved Engel I outcomes. Prognosis was correlated with factors such as age at surgery, MRI findings, invasive EEG, pathology, acute postoperative seizures (APOS), and the number of preoperative and postoperative anti-seizure medications (AEDs). Age at surgery and the number of preoperative AEDs (p < 0.001) were significant predictors of seizure recurrence. Distinct clinical characteristics were observed among different age groups.
CONCLUSIONS: Surgery is effective in terminating MCD-related DRE. Younger age at surgery and fewer preoperative AEDs are associated with better prognoses. Clinical characteristics vary significantly with age.

Malformation of cortical development is an important cause of drug-resistant epilepsy in young children. Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) has been added to the last focal cortical dysplasia (FCD) classification and commonly involves the frontal lobe. The semiology at the onset of epilepsy is dominated by non-lateralizing infantile spasm; the boundaries of the malformation are usually difficult to determine by magnetic resonance imaging (MRI) and positron emission tomography (PET), and electroencephalography (EEG) findings are often widespread. Therefore, the traditional concept and strategy of preoperative evaluation to determine the extent of the epileptogenic zone by comprehensive anatomo-electro-clinical methods are difficult to implement. Frontal disconnection is an effective surgical method for the treatment of epilepsy, but there are few related reports. A total of 8 children with histo-pathologically confirmed MOGHE were retrospectively studied. MOGHE was located in the frontal lobe in all patients, and frontal disconnection was performed. The periinsular approach was used in the disconnective procedures, divided into several surgical steps: the partial inferior frontal gyrus resection, the frontobasal and intrafrontal disconnection, and the anterior corpus callosotomy. One patient presented with a short-term postoperative speech disorder, while another patient exhibited transient postoperative limb weakness. No long-term postoperative complications were observed. At 2 years after surgery, 75% of patients were seizure-free, with cognitive improvement in half of them. This finding suggested that frontal disconnection is an effective and safe surgical procedure for the treatment of MOGHE instead of extensive resection in the frontal lobe.

暂无摘要。

Focal cortical dysplasia type I (FCD I) is the most common cause of pharmaco-resistant epilepsy with the poorest prognosis. To understand the epileptogenic mechanisms of FCD I, we obtained tissue resected from patients with FCD I epilepsy, and from tumor patients as control. Using whole-cell patch clamp in acute human brain slices, we investigated the cellular properties of fast-spiking interneurons (FSINs) and pyramidal neurons (PNs) within the ictal onset zone. In FCD I epilepsy, FSINs exhibited lower firing rates from slower repolarization and action potential broadening, while PNs had increased firing. Importantly, excitatory synaptic drive of FSINs increased progressively with the scale of cortical activation as a general property across species, but this relationship was inverted towards net inhibition in FCD I epilepsy. Further comparison with intracranial electroencephalography (iEEG) from the same patients revealed that the spatial extent of pathological high-frequency oscillations (pHFO) was associated with synaptic events at FSINs.

暂无摘要。

Brain malformations represent a heterogeneous group of abnormalities of neural morphogenesis, often associated with aberrations of neuronal connectivity and brain volume. Prenatal detection of brain malformations requires a clear understanding of embryology and developmental morphology through the various stages of gestation. This expert panel review is written with the central aim of providing an easy-to-understand roadmap to improve prenatal detection and characterization of structural malformations based on the current understanding of normal and aberrant brain development. The utility of each available neuroimaging modality including prenatal multiplanar neurosonography, anatomical magnetic resonance imaging (MRI), and advanced MRI techniques, as well as further insights from post-mortem imaging have been highlighted for every developmental stage.

Malformations of cortical development (MCD) are a group of developmental disorders characterized by abnormal cortical structures caused by genetic or harmful environmental factors. Many kinds of MCD are caused by genetic variation. MCD is the common cause of intellectual disability and intractable epilepsy. With rapid advances in imaging and sequencing technologies, the diagnostic rate of MCD has been increasing, and many potential genes causing MCD have been successively identified. However, the high genetic heterogeneity of MCD makes it challenging to understand the molecular pathogenesis of MCD and to identify effective targeted drugs. Thus, in this review, we outline important events of cortical development. Then we illustrate the progress of molecular genetic studies about MCD focusing on the PI3K/PTEN/AKT/mTOR pathway. Finally, we briefly discuss the diagnostic methods, disease models, and therapeutic strategies for MCD. The information will facilitate further research on MCD. Understanding the role of the PI3K/PTEN/AKT/mTOR pathway in MCD could lead to a novel strategy for treating MCD-related diseases.

OBJECTIVE: To evaluate the diagnostic capabilities of modifying the standard MRI protocol as part of an interdisciplinary presurgical examination of patients with epileptogenic substrates of unknown etiology.
METHODS: The results of dynamic MRI of 8 patients with a referral diagnosis of focal cortical dysplasia (FCD) were analyzed. In 7 patients, epilepsy was the reason for a standard MRI of the brain; in another patient with myasthenia, MRI was performed as part of a comprehensive examination. All patients, in addition to standard MRI, underwent a modification of the real-time scanning protocol to include contrast, tractography (DTI), and perfusion techniques (ASL/DSC). In 1 case, with questionable results, the results of a modification of the standard MRI protocol, high-resolution MRI (HR MRI) and hybrid positron emission CT with 11C-methionine (PET/CT with 11C-MET) were combined.
RESULTS: Seven patients underwent epileptic surgery and 1 patient was operated on for a tumor. In 4 out of 8 patients, based on the results of a modification of the standard MRI protocol, radiological signs of a neoplastic process were identified, which suggested a low-grade tumor. One of them needed PET/CT to confirm the assumption. The results of pathomorphological examination correlated with the direct diagnosis for surgical treatment. One of the 4 patients was suspected to have dysembryoplastic neuroepithelial tumor (DNET) based on the results of the protocol modification, which was also confirmed by pathological examination. In another 4 patients in whom it was possible to narrow the differential between FCD type II and DNET based on the results of the modification, FCD IIb was pathomorphologically verified.
CONCLUSIONS: The proposed modification of the standard MRI protocol can significantly facilitate the differential diagnosis between the neoplastic and dysplastic origin of an epileptogenic substrate of unknown etiology, which in turn affects the patient\'s management tactics.
UNASSIGNED: Оценить диагностические возможности модификации стандартного протокола МРТ в рамках междисциплинарного прехирургического обследования пациентов с эпилептогенными субстратами неясной этиологии.
UNASSIGNED: Проанализированы результаты динамических МРТ 8 пациентов с предположительным диагнозом «фокальная кортикальная дисплазия» (ФКД). У 7 пациентов поводом для проведения стандартной МРТ головного мозга явилась эпилепсия, у 1 пациента с миастенией МРТ проведена в ходе комплексного обследования. Всем пациентам дополнительно к стандартной МРТ выполнен модифицированный протокол сканирования в режиме реального времени, включая контрастирование, трактографию (DTI), оценку перфузии (ASL/DSC). При сомнительных результатах у 1 больного проведено совмещение результатов модифицированного протокола стандартной МРТ, МРТ высокого разрешения (МРТ ВР) и гибридной позитронно-эмиссионной КТ с 11C-метионином (ПЭТ/КТ с 11С-МЕТ).
UNASSIGNED: Процедуру эпилептической хирургии прошли 7 пациентов, 1 — прооперирован по поводу опухоли. У 4 из 8 пациентов по результатам модифицированного протокола стандартной МРТ были выявлены радиологические признаки неопластического процесса, позволившие предположить опухоль низкой степени злокачественности. Одному пациенту понадобилось проведение ПЭТ/КТ для подтверждения диагноза. Результаты патоморфологического исследования коррелировали с направляющим диагнозом на хирургическое лечение. У 1 из 4 пациентов была предположена дизэмбриопластическая нейроэпителиальная опухоль (ДНЭО), основываясь на результатах модифицированного протокола, что было подтверждено при патоморфологическом исследовании. Еще у 4 пациентов, у которых удалось сузить дифференциально диагностический ряд между ФКД II типа и ДНЭО, по результатам модифицированной МРТ патоморфологически верифицирована ФКД IIb.
UNASSIGNED: Предложенная модификация стандартного протокола МРТ может существенно облегчить проведение дифференциальной диагностики между неопластическим и диспластическим происхождением эпилептогенного субстрата неясной этиологии, что влияет на тактику ведения пациента.

OBJECTIVE: Assessing the diagnostic significance of MR morphometry in determining the localization of focal cortical dysplasias (FCD).
METHODS: The study included 13 children after surgery for drug-resistant epilepsy caused by FCD type II and stable postoperative remission of seizures (Engel class IA, median follow-up 56 months). We analyzed the results of independent expert assessment of native MR data by three radiologists (HARNESS protocol) and MR morphometry data regarding accuracy of FCD localization. We considered 2 indicators, i.e. local cortical thickening and gray-white matter blurring.
RESULTS: FCD detection rate was higher after MR morphometry compared to visual analysis of native MR data using the HARNESS protocol. MR morphometry also makes it possible to more often identify gray-white matter blurring as a sign often missed by radiologists (p<0.05).
CONCLUSIONS: MR morphometry is an additional non-invasive method for assessing the localization of FCD.
UNASSIGNED: Оценка диагностической значимости магнитно-резонансной (МР) морфометрии в определении локализации фокальных кортикальных дисплазий (ФКД).
UNASSIGNED: В исследование включены 13 детей, оперированных по поводу фармакорезистентной структурной эпилепсии, обусловленной ФКД II типа, с исходом в стойкую ремиссию приступов (Engel class IA, медиана катамнеза 56 мес). Проведен сравнительный анализ результатов экспертной независимой оценки трех рентгенологов нативных МР-данных по протоколу HARNESS с данными МР-морфометрии в точности локализации ФКД по двум показателям: локальному утолщению коры и размытости перехода серого и белого вещества.
UNASSIGNED: Частота выявления зон с ФКД была выше после проведения МР-морфометрии по сравнению с визуальным анализом нативных МР-данных по протоколу HARNESS. МР-морфометрия также позволяет чаще выявлять зоны размытости перехода серого вещества в белое — признак, часто пропускаемый врачами-рентгенологами (p<0,05).
UNASSIGNED: Метод МР-морфометрии является дополнительным неинвазивным методом оценки локализации ФКД.

Somatic mutations have been identified in 10% to 63% of focal cortical dysplasia type II samples, primarily linked to the mTOR pathway. When the causative genetic mutations are not identified, this opens the possibility of discovering new pathogenic genes or pathways that could be contributing to the condition. In our previous study, we identified a novel candidate pathogenic somatic variant of IRS-1 c.1791dupG in the brain tissue of a child with focal cortical dysplasia type II. This study further explored the variant\'s role in causing type II focal cortical dysplasia through in vitro overexpression in 293T and SH-SY5Y cells and in vivo evaluation via in utero electroporation in fetal brains, assessing effects on neuronal migration, morphology, and network integrity. It was found that the mutant IRS-1 variant led to hyperactivity of p-ERK, increased cell volume, and was predominantly associated with the MAPK signaling pathway. In vivo, the IRS-1 c.1791dupG variant induced abnormal neuron migration, cytomegaly, and network hyperexcitability. Notably, the ERK inhibitor GDC-0994, rather than the mTOR inhibitor rapamycin, effectively rescued the neuronal defects. This study directly highlighted the ERK signaling pathway\'s role in the pathogenesis of focal cortical dysplasia II and provided a new therapeutic target for cases of focal cortical dysplasia II that are not treatable by rapamycin analogs.