Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy. Dysmorphic neurons are the major histopathological feature of type II FCD, but their role in seizure genesis in FCD is unclear. Here we performed whole-cell patch-clamp recording and morphological reconstruction of cortical principal neurons in postsurgical brain tissue from drug-resistant epilepsy patients. Quantitative analyses revealed distinct morphological and electrophysiological characteristics of the upper layer dysmorphic neurons in type II FCD, including an enlarged soma, aberrant dendritic arbors, increased current injection for rheobase action potential firing, and reduced action potential firing frequency. Intriguingly, the upper layer dysmorphic neurons received decreased glutamatergic and increased GABAergic synaptic inputs that were coupled with upregulation of the Na⁺-K⁺-Cl^- cotransporter. In addition, we found a depolarizing shift of the GABA reversal potential in the CamKII-cre::PTEN^flox/flox mouse model of drug-resistant epilepsy, suggesting that enhanced GABAergic inputs might depolarize dysmorphic neurons. Thus, imbalance of synaptic excitation and inhibition of dysmorphic neurons may contribute to seizure genesis in type II FCD.
Animals ; Drug Resistant Epilepsy/surgery* ; Epilepsy/pathology* ; Malformations of Cortical Development/pathology* ; Malformations of Cortical Development, Group I ; Mice ; Neurons/pathology* ; Seizures/pathology*

OBJECTIVETo study the clinicopathologic features of tuberous sclerosis complex (TSC).

METHODSThe clinicopathologic data of the patients diagnosed as TSC with refractory epilepsy and resection of epileptic focus were retrospectively analyzed.

RESULTSFourteen cases were included, the mean age was (15.8±12.9) years, with a male predominance (male to female ratio=10:4). Frontal lobe was the most common (13/14) site of involvement. MRI showed multiple patchy long T1 and long T2 signals. CT images showed multiple subependymal high density calcified nodules in nine cases. Histology showed mild to severe disruption of the cortical lamination, cortical and subcortical tubers with giant cells and/or dysmorphic neurons. The giant cells showed strong immunoreactivity for vimentin and nestin, while the dysmorphic neurons partially expressed MAP2 and NF. Vimentin also stained strongly the "reactive" astrocytes. Thirteen cases had follow-up information: Engel class I in six cases, Engel class II in six cases, and Engel class III in one case.

CONCLUSIONSDiagnosis of TSC relies on combined pathologic, clinical and neuroradiological features. Immunohistochemical staining can be helpful. Resection of epileptic focus is an effective method to treat refractory epilepsy in TSC.

Adolescent ; Astrocytes ; chemistry ; pathology ; Child ; Drug Resistant Epilepsy ; surgery ; Epilepsy ; complications ; metabolism ; pathology ; Epilepsy, Frontal Lobe ; complications ; metabolism ; pathology ; Female ; Giant Cells ; chemistry ; pathology ; Humans ; Magnetic Resonance Imaging ; Male ; Nestin ; analysis ; Neurons ; metabolism ; pathology ; Retrospective Studies ; Tuberous Sclerosis ; complications ; metabolism ; pathology ; Vimentin ; analysis

Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) may be a promising modality for treating medial temporal lobe epilepsy. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a noninvasive method for monitoring in vivo glucose metabolism. We evaluated the efficacy of hUCB-MSCs transplantation in chronic epileptic rats using FDG-PET. Rats with recurrent seizures were randomly assigned into three groups: the stem cell treatment (SCT) group received hUCB-MSCs transplantation into the right hippocampus, the sham control (ShC) group received same procedure with saline, and the positive control (PC) group consisted of treatment-negative epileptic rats. Normal rats received hUCB-MSCs transplantation acted as the negative control (NC). FDG-PET was performed at pre-treatment baseline and 1- and 8-week posttreatment. Hippocampal volume was evaluated and histological examination was done. In the SCT group, bilateral hippocampi at 8-week after transplantation showed significantly higher glucose metabolism (0.990 +/- 0.032) than the ShC (0.873 +/- 0.087; P < 0.001) and PC groups (0.858 +/- 0.093; P < 0.001). Histological examination resulted that the transplanted hUCB-MSCs survived in the ipsilateral hippocampus and migrated to the contralateral hippocampus but did not differentiate. In spite of successful engraftment, seizure frequency among the groups was not significantly different. Transplanted hUCB-MSCs can engraft and migrate, thereby partially restoring bilateral hippocampal glucose metabolism. The results suggest encouraging effect of hUCB-MSCs on restoring epileptic networks.
Animals ; Chronic Disease ; Cord Blood Stem Cell Transplantation/*methods ; Epilepsy, Temporal Lobe/*metabolism/pathology/*therapy ; Fluorodeoxyglucose F18/*pharmacokinetics ; Hippocampus/*metabolism/*pathology/surgery ; Male ; Mesenchymal Stem Cell Transplantation/methods ; Radiopharmaceuticals/pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Sensitivity and Specificity ; Tissue Distribution ; Treatment Outcome

BACKGROUNDThe aim of this study is to explore the treatment and outcome of epileptogenic temporal lobe cavernous malformations (CMs).

METHODSWe analyzed retrospectively the profiles of 52 patients diagnosed as temporal lobe CMs associated with epilepsy. Among the 52 cases, 11 underwent a direct resection of CM along with the adjacent zone of hemosiderin rim without electrocorticogram (ECoG) monitoring while the other 41 cases had operations under the guidance of ECoG. Forty-six patients were treated by lesionectomy + hemosiderin rim while the other six were treated by lesionectomy + hemosiderin rim along with extended epileptogenic zone resection. The locations of lesions, the duration of illness, the manifestation, the excision ranges and the outcomes of postoperative follow-up were analyzed, respectively.

RESULTSAll of the 52 patients were treated by microsurgery. There was no neurological deficit through the long-term follow-up. Outcomes of seizure control are as follows: 42 patients (80.8%) belong to Engel Class I, 5 patients (9.6%) belong to Engel Class II, 3 patients (5.8%) belong to Engel Class III and 2 patients (3.8%) belong to Engel Class IV.

CONCLUSIONPatients with epilepsy caused by temporal CMs should be treated as early as possible. Resection of the lesion and the surrounding hemosiderin zone is necessary. Moreover, an extended excision of epileptogenic cortex or cerebral lobes is needed to achieve a better prognosis if the ECoG indicates the existence of an extra epilepsy onset origin outside the lesion itself.

Adolescent ; Adult ; Child ; Electroencephalography ; Epilepsy ; surgery ; Female ; Hemangioma, Cavernous, Central Nervous System ; surgery ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Temporal Lobe ; pathology ; surgery ; Treatment Outcome ; Young Adult

PURPOSE: This study was conducted to assess the clinical relevance of diffusion tensor tractography (DTT) in pre- and post-operative evaluations of childhood epilepsy surgery. MATERIALS AND METHODS: Seventy-two patients who received epilepsy surgery between March 2004 and July 2008 were retrospectively analyzed (M : F=40 : 32, ages of 3 months to 24 years, mean age=8.9 years). DTT was performed using a 3.0 T scanner and single-shot spin-echo echo-planar imaging with 32-different diffusion gradient directions. We reviewed the data focusing on the type of surgery, final pathological diagnosis, and how the DTT data were clinically used. RESULTS: The most common form of childhood epilepsy surgery was complete resection of an epileptogenic lesion (n=52, 72.2%). The reported etiologies included cortical dysplasia (n=32, 44.4%), hippocampal sclerosis (n=9, 12.5%), brain tumors (n=7, 9.7%), and non-pathologic lesions (n=4, 5.6%) in the final diagnoses. Twenty-one dysplastic cortexes and four brain tumors involved an approximal relationship with the corticospinal tract (n=18), optic radiation (n=2), and arcuate fasciculus (n=5). Additionally, although DTT demonstrated white matter tracts clearly, DTT in the hippocampal sclerosis did not provide any additional information. In cases of callosotomy (n=18, 25%), post-operative DTT was utilized for the evaluation of complete resection in all patients. DTT information was not used in functional hemispherectomy (n=2, 2.8%). CONCLUSION: Preoperatively, DTT was a useful technique in cases of cortical dysplasia and brain tumors, and in cases with callosotomy, postoperatively. DTT should be included among the routine procedures performed in management of epilepsy.
Adolescent ; Adult ; Brain Neoplasms/pathology/surgery ; Child ; Child, Preschool ; Diffusion Tensor Imaging/*methods ; Epilepsy/*pathology/*surgery ; Female ; Hippocampus/pathology ; Humans ; Infant ; Male ; Retrospective Studies ; Sclerosis/pathology/surgery ; Seizures/surgery ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate pathological changes in the epileptogenic foci of children with intractable epilepsy and their clinical significance.

METHODSThirty children with intractable epilepsy were included in the study. The epileptogenic foci were surgically resected and pathological changes in the obtained specimens were observed under a light microscope (LM) and a transmission electron microscope (TEM).

RESULTSUnder the LM, cortical dysplasia was found in 14 cases (47%), hippocampal sclerosis in 11 cases (37%), dysembryoplastic neuroepithelial tumor in 1 case (3%), ganglioglioma in 1 case (3%), and encephalomalacia in 3 cases (10%). The TEM observation revealed pathological changes in the ultrastructure of the hippocampus and extra-hippocampal cortex, such as changes in the number of synapses and synaptic structure, decrease in neurons and karyopyknosis, swelling and degeneration of astrocytes, and changes in mitochondrial structures.

CONCLUSIONSPathological changes in the hippocampus and extra-hippocampal cortex, especially synaptic remodeling, may be the morphological basis for spontaneous recurrent seizures in children with intractable epilepsy. The pathological changes and epileptiform activity are related to an imbalance between excitatory and inhibitory neurotransmission.

Adolescent ; Brain ; pathology ; ultrastructure ; Cerebral Cortex ; pathology ; ultrastructure ; Child ; Child, Preschool ; Epilepsy ; pathology ; surgery ; Female ; Hippocampus ; pathology ; ultrastructure ; Humans ; Infant ; Intelligence ; Male ; Microscopy, Electron, Transmission

OBJECTIVETo investigate the clinicopathologic features of the brain tissue diagnosed as ulegyria from modified anatomic hemispherectomy for refractory epilepsy.

METHODSThe clinical and pathologic findings were reviewed in 39 patients who underwent modified anatomic hemispherectomy and diagnosed as ulegyria in the Epilepsy Center of Tsinghua University Yuquan Hospital from 2007 to 2011.

RESULTSAll patients including 30 males and 9 females had medically intractable seizures, and the mean age of seizure onset and disease duration were 4.0 years and 7.3 years respectively. Significant history included febrile seizure in 14 patients (35.9%), cerebral hemorrhage in 8 patients (20.5%), fetal distress and surgical trauma each in 6 patients (15.4%), vascular malformation and cerebral hemorrhage in 1 patient (2.6%), and unclear history in 4 patients (10.2%). Histologically, all cases were characterized by cortical destruction, with neuronal loss and gliosis. All cases were accompanied by varying degree of cortical dysplasia, which were diagnosed as focal cortical dysplasia IIId. Hippocampus sclerosis was identified in 2 cases. Seizure outcome after surgery revealed 37 patients (94.9%) had an Engel grade I, two patients (5.1%) had an Engel grade II.

CONCLUSIONSFebrile seizure, cerebral hemorrhage, fetal distress and surgical trauma in childhood can lead to refractory epilepsy. Histopathological change in the brain is ulegyria accompanied by focal cortical dysplasia IIId. Modified anatomic hemispherectomy is an effective therapy to treat those patients with extensive changes of one hemisphere.

Adolescent ; Adult ; CD3 Complex ; metabolism ; Cerebral Cortex ; abnormalities ; pathology ; surgery ; Child ; Child, Preschool ; Epilepsy ; metabolism ; pathology ; surgery ; Female ; Follow-Up Studies ; Hemispherectomy ; methods ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Malformations of Cortical Development ; metabolism ; pathology ; surgery ; Retrospective Studies ; Young Adult

Cerebral Cortex ; physiology ; Electric Stimulation Therapy ; Electroencephalography ; Epilepsy ; pathology ; physiopathology ; surgery ; Female ; Glioma ; pathology ; physiopathology ; surgery ; Humans ; Middle Aged

Few studies have included magnetoencephalography (MEG) when assessing the diagnostic value of presurgical modalities in a nonlesional epilepsy population. Here, we compare single photon emission computed tomography (SPECT), positron emission tomography (PET), video-EEG (VEEG), and MEG, with intracranial EEG (iEEG) to determine the value of individual modalities to surgical decisions. We analyzed 23 adult epilepsy patients with no abnormal MRI findings who had undergone surgical resection. Localization of individual presurgical tests was determined for hemispheric and lobar locations based on visual analysis. Each localization result was compared with the ictal onset zone (IOZ) defined by using iEEG. The highest to the lowest hemispheric concordance rates were MEG (83%) > ictal VEEG (78%) > PET (70%) > ictal SPECT (57%). The highest to lowest lobar concordance rates were ictal VEEG = MEG (65%) > PET (57%) > ictal SPECT (52%). Statistical analysis showed MEG to have a higher hemispheric concordance than that of ictal SPECT (P = 0.031). We analyzed the effects of MEG clustered-area resection on surgical outcome. Patients who had resection of MEG clusters showed a better surgical outcome than those without such resection (P = 0.038). It is suggested that MEG-based localization had the highest concordance with the iEEG-defined IOZ. Furthermore, MEG cluster resection has prognostic significance in predicting surgical outcome.
Adolescent ; Adult ; Brain/*pathology/surgery ; *Brain Mapping ; Electroencephalography ; Epilepsy/*radionuclide imaging/surgery ; Female ; Humans ; Magnetic Resonance Imaging ; *Magnetoencephalography ; Male ; Middle Aged ; Positron-Emission Tomography ; Preoperative Care ; Tomography, Emission-Computed, Single-Photon ; Video Recording

Few studies have included magnetoencephalography (MEG) when assessing the diagnostic value of presurgical modalities in a nonlesional epilepsy population. Here, we compare single photon emission computed tomography (SPECT), positron emission tomography (PET), video-EEG (VEEG), and MEG, with intracranial EEG (iEEG) to determine the value of individual modalities to surgical decisions. We analyzed 23 adult epilepsy patients with no abnormal MRI findings who had undergone surgical resection. Localization of individual presurgical tests was determined for hemispheric and lobar locations based on visual analysis. Each localization result was compared with the ictal onset zone (IOZ) defined by using iEEG. The highest to the lowest hemispheric concordance rates were MEG (83%) > ictal VEEG (78%) > PET (70%) > ictal SPECT (57%). The highest to lowest lobar concordance rates were ictal VEEG = MEG (65%) > PET (57%) > ictal SPECT (52%). Statistical analysis showed MEG to have a higher hemispheric concordance than that of ictal SPECT (P = 0.031). We analyzed the effects of MEG clustered-area resection on surgical outcome. Patients who had resection of MEG clusters showed a better surgical outcome than those without such resection (P = 0.038). It is suggested that MEG-based localization had the highest concordance with the iEEG-defined IOZ. Furthermore, MEG cluster resection has prognostic significance in predicting surgical outcome.
Adolescent ; Adult ; Brain/*pathology/surgery ; *Brain Mapping ; Electroencephalography ; Epilepsy/*radionuclide imaging/surgery ; Female ; Humans ; Magnetic Resonance Imaging ; *Magnetoencephalography ; Male ; Middle Aged ; Positron-Emission Tomography ; Preoperative Care ; Tomography, Emission-Computed, Single-Photon ; Video Recording