OBJECTIVES:The purpose of the study was to investigate the abnormalities of cortical lamination observed in temporal lobe specimens obtained during surgery for intractable temporal lobe epilepsy (TLE) with hippocampal sclerosis. Specifically, we aimed to 1) correlate high-field ex vivo MRI with histopathologic analysis and 2) evaluate the effect of tissue fixation on image contrast.METHODS:A cohort of 13 specimens was considered. T2-weighted imaging and relaxometry were performed during and after fixation using a 7-T experimental scanner. After imaging, the specimens were studied with histopathologic (Black Gold myelin fiber staining) and immunohistochemical (NeuN neuronal staining) methods in order to explore the correspondence between MRI and histopathologic features.RESULTS:The principal findings of this study are that 1) superior MRI contrast is obtained among the cortical layers using completely fixed specimens as opposed to recently excised tissue, 2) the intensity of the T2-weighted MRI signal is lowest (hypointensity) at the site of highest fiber concentration and cellular density, and highest (hyperintensity) when the density of fibers and cells is lowest, and 3) the MRI signal is altered in presence of abnormal cortical lamination (focal cortical dysplasia type IA).CONCLUSIONS:High resolution ex vivo MRI enables the study of intracortical organization in normal and pathologic areas. Comparisons between MRI, NeuN, and Black Gold indicate that the differences apparent in T2-weighted images are mainly related to fiber concentration, although neuronal density might also play a role.

Graceful aging has been associated with frontal hyperactivations in working- and episodic long-term memory tasks, a compensatory process, according to some, that allows the best normal elders to perform these tasks at a juvenile level, in spite of natural cortical impoverishment. In this study, 24 young and 24 healthy elderly participants were compared. Graceful aging was explored by investigating domains where most healthy elders perform like youngers (e.g. lexical-semantic knowledge) and tasks that are typically more challenging, like episodic long-term recognition memory tasks. With voxel-based morphometry, we also studied to what extent changes of fMRI activation were consistent with the pattern of brain atrophy. We found that hyperactivations and hypoactivations of the elders were not restricted to the frontal lobes, rather they presented with task-dependent patterns. Only hypoactivations and normal levels of activation systematically overlapped with regional atrophy. We conclude that compensatory processes associated with graceful aging may not necessarily be a sign of early saturation of executive resources, if this was to be represented by a systematic frontal hyperactivation, but rather they may represent the ability of recruiting new cognitive strategies. We discuss two possible approaches to further test this hypothesis.

In 2000 Baddeley proposed the existence of a new component of working memory, the episodic buffer, which should contribute to the on-line maintenance of integrated memory traces. The author assumed that this component should be critical for immediate recall of a short story that exceeds the capacity of the phonological store. Accordingly, patients with Alzheimer’s dementia (AD) should suffer of a deficit of the episodic buffer when immediate recall of a short story is impossible. On the other hand, the episodic buffer should be somewhat preserved in such patients when some IR can occur (Baddeley and Wilson, 2002). We adopted this logic for a voxel-based morphometry study. We compared the distribution of grey-matter density of two such groups of AD patients with a group of age-matched controls. We found that both AD groups had a significant atrophy of the left mid-hippocampus; on the other hand, the anterior part of the hippocampus was significantly more atrophic in patients who were also impaired on the immediate prose recall task. Six out of ten patients with no immediate recall were spared at “central executive” tasks. Taken together our findings suggest that the left anterior hippocampus contributes to the episodic buffer of the revised working memory model. We also suggest that the episodic buffer is somewhat independent from the central executive component of working memory.

Of the cases with nocturnal frontal lobe epilepsy (NFLE) approximately 30% are refractory to antiepileptic medication, with several patients suffering from the effects of both ongoing seizures and disrupted sleep. From a consecutive series of 522 patients operated on for drug-resistant focal epilepsy, 21 cases (4%), whose frontal lobe seizures occurred almost exclusively (>90%) during sleep, were selected. All patients underwent a comprehensive pre-surgical evaluation, which included history, interictal EEG, scalp video-EEG monitoring, high-resolution MRI and, when indicated, invasive recording by stereo-EEG (SEEG). There were 11 males and 10 females, whose mean age at seizure onset was 6.2 years, mean age at surgery was 24.7 years and seizure frequency ranged from <20/month to >300/month. Nine patients reported excessive daytime sleepiness (EDS). Prevalent ictal clinical signs were represented by asymmetric posturing (6 cases), hyperkinetic automatisms (10 cases), combined tonic posturing and hyperkinetic automatisms (4 cases) and mimetic automatisms (1 case). All patients reported some kind of subjective manifestations. Interictal and ictal EEG provided lateralizing or localizing information in most patients. MRI was unrevealing in 10 cases and it showed a focal anatomical abnormality in one frontal lobe in 11 cases. Eighteen patients underwent a SEEG evaluation to better define the epileptogenic zone (EZ). All patients received a microsurgical resection in one frontal lobe, tailored according to pre-surgical evaluations. Two patients were operated on twice owing to poor results after the first resection. Histology demonstrated a Taylor-type focal cortical dysplasia (FCD) in 16 patients and an architectural FCD in 4. In one case no histological change was found. After a post-operative follow-up of at least 12 months (mean 42.5 months) all the 16 patients with a Taylor's FCD were in Engel's Class Ia and the other 5 patients were in Engel's Classes II or III. After 6 months post-surgery EDS had disappeared in the 9 patients who presented this complaint pre-operatively. It is concluded that patients with drug-resistant, disabling sleep-related seizures of frontal lobe origin should be considered for resective surgery, which may provide excellent results both on seizures and on epilepsy-related sleep disturbances. An accurate pre-surgical evaluation, which often requires invasive EEG recording, is mandatory to define the EZ. Further investigation is needed to explain the possible causal relationships between FCD, particularly Taylor-type, and sleep-related seizures, as observed in this cohort of NFLE patients.

Hyperkinetic seizures are considered a typical manifestation of nocturnal frontal lobe epilepsy (NFLE). Patients with temporal lobe epilepsy with mainly sleep-related seizures have been described; however they commonly lack hyperkinetic activity and seizure frequency is low. We retrospectively analysed our population of 442 consecutive patients surgically treated between January 1996 and January 2004. Among these there were 25 patients with sleep-related hyperkinetic epileptic seizures, with a frontal lobe onset in 18 cases and a temporal lobe onset in 7. Patients with sleep-related hyperkinetic seizures with temporal lobe origin had anamnestic and clinical features strikingly similar to those with a frontal onset, with agitated movements, high seizure frequency and no history of febrile convulsions. We confirm our previous findings that this kind of epileptic manifestation is not only peculiar to frontal lobe epilepsy.

OBJECTThe authors report on indications for, techniques of, and results of stereoelectroencephalography (stereo-EEG) monitoring in the presurgical evaluation of childhood drug-resistant focal epilepsy.METHODSThirty-five children (24 boys and 11 girls; mean age 8.8 +/- 3.9 years; mean age at seizure onset 2.1 +/- 2.2 years) underwent 37 tailored stereotactic placements of intracerebral, multilead electrodes for intensive monitoring of seizures (stereo-EEG). Two children underwent exploration twice. Investigations prior to stereo-EEG monitoring, including magnetic resonance imaging and video-EEG of the scalp, revealed variable patterns of localizing incoherence among clinical, electrophysiological, and anatomical findings in all cases. A total of 426 electrodes were implanted (mean 11.5 +/- 2.6 per procedure) according to individualized arrangements. The stereo-EEG monitoring enabled recording of 826 seizures (mean 22 +/- 45 per procedure) and mapping of critically functional areas. One untoward event consisted of intracranial breakage of an electrode. Resections of the epileptogenic zone were performed according to results of stereo-EEG recordings. They consisted of cortical removal in seven cases, removal of the lesion and epileptogenic cortex in 26 cases, and lesion removal in two cases. Transient postoperative neurological deficits were observed in 13 patients, and permanent anticipated visual field defects occurred in seven patients. According to the Engel postoperative classification of seizure outcome, 60% of cases were in Class I, 74% had significant improvement (Classes I-III), and 26% were unchanged (mean follow up 31.9 +/- 20.6 months).CONCLUSIONSStereoelectroencephalography monitoring is a helpful and well-tolerated technique for the definition of the epileptogenic zone in complex cases of childhood drug-resistant epilepsy. It provides essential information for safe resections that should result in excellent outcomes in a considerable number of patients.

We present the results of a retrospective study on 10 patients operated on for intractable epilepsy associated with nodular heterotopia as identified by high resolution MRI. Seven patients had unilateral heterotopia, one patient had symmetric bilateral heterotopia and two patients had asymmetric bilateral heterotopia. By stereo-electroencephalogram (SEEG) (nine patients) interictal activity within nodules was similar in all cases, and ictal activity never started from nodules alone but from the overlying cortex or simultaneously in nodules and cortex. Excellent outcomes (Engel class Ia, 1987) were achieved in the seven patients with unilateral heterotopia, showing that surgery can be highly beneficial in such cases when the epileptogenic zone is carefully located prior to surgery by MRI and particularly SEEG. For the bilateral cases surgical outcomes were Engel IIa (one patient) or Engel IIIa (two patients). Histological/immunohistochemical studies of resected specimens showed that all nodules had similar microscopic organization, even though their extent and location varied markedly. The overlying cortex was dysplastic in nine patients, but of normal thickness. We suggest that nodule formation may be the result of a dual mechanism: (i) failure of a stop signal in the germinal periventricular region leading to cell overproduction; and (ii) early transformation of radial glial cells into astrocytes resulting in defective neuronal migration. The intrinsic interictal epileptiform activity of nodules may be due to an impaired intranodular GABAergic system.

BACKGROUND AND PURPOSE: Focal cortical dysplasia (FCD) covers a spectrum of conditions in which the neuropathologic and electroclinic presentations and the surgical outcomes vary. The aim of this study was to identify the MR features of histologic subtypes of FCD that would be useful for differential diagnosis. METHODS: We reviewed the MR data of 49 patients treated surgically for intractable partial epilepsy, who received a histologic diagnosis of FCD not associated with other brain abnormalities except hippocampal sclerosis and who were classified by histologic criteria as having architectural dysplasia (28 patients), cytoarchitectural dysplasia (six patients), or Taylor’s FCD (15 patients). RESULTS: From the MR features, it was generally possible to distinguish Taylor’s FCD from architectural or cytoarchitectural dysplasias (non-Taylor’s FCD). Findings suggesting Taylor’s FCD were focal cortical thickening, blurring of the gray-white matter junction, and hyperintensity (on T2-weighted images) of subcortical white matter often tapering toward the ventricle. Focal brain hypoplasia with shrinkage and moderate signal intensity alterations in the white matter core were present in most patients with architectural dysplasia. The lesion was generally extratemporal in Taylor’s FCD and temporal in architectural dysplasia. Ipsilateral hippocampal sclerosis was often present in architectural dysplasia (dual abnormality). CONCLUSIONS: In patients with FCD, Taylor’s FCD and non-Taylor’s FCD can usually be distinguished with MR imaging, although some overlap exists. A provisional MR diagnosis is important for presurgical investigations and surgical planning and may have prognostic implications.

Malformations of cortical development may be associated with drug-resistant partial epilepsy suitable for surgical therapy. From the anatomopathological point of view, this categorisation has been used in reference to a wide range of alterations of the cortical mantle. Focal cortical dysplasias represent the main group of malformations of cortical development, but there are also other types of alterations, such as heterotopias, double cortex or polymicrogyria. Defining candidacy for surgical therapy and tailored resection requires thorough pre-surgical evaluation so that the approach will be individualised for each patient. We present our series of 126 patients with malformation of cortical development selected from 321 consecutively operated patients. Within this group encompassing different types of malformation of cortical development, including periventricular heterotopia (nine patients), polymicrogyria (three patients), hemimegalencephaly (one patient) and subcortical band heterotopia (one patient), the largest group was 81 individuals with focal cortical dysplasia. For this last group, we propose a simplified classification defining 42 architectural dysplasias, 12 cytoarchitectural dysplasias and 27 Taylor's focal cortical dysplasias. In addition, at routine neuropathological investigation, the only morphological alteration shown by 31 patients was diffuse neuronal heterotopia. All patients underwent scalp EEG and video-EEG, and 75 patients (59.5%) also underwent stereo-EEG. Magnetic resonance imaging and stereotactic stereoscopic angiography represented the indispensable premises for further studies, in particular stereo-EEG, and for planning surgery and tailoring resection. Magnetic resonance imaging was unhelpful in 17 out of 81 patients with focal cortical dysplasia and in seven out of 31 with neuronal heterotopia, while signal alterations were present in all other cases. Common characteristics corresponding to clinical-histopathological homogeneous subgroups were found within the focal cortical dysplasia group. In patients with architectural dysplasia, the epileptogenic zone was mainly in the temporal lobe and there was a lower seizure frequency than in patients with Taylor's focal cortical dysplasia. Patients with Taylor's type had an epileptogenic zone that was mainly extra-temporal, and a distinctive interictal stereo-EEG. The best outcome was observed in patients with Taylor's type dysplasia: 69% seizure-free (Engel class Ia) after at least 1 year of follow-up, compared with 45% of cytoarchitectural dysplasia and 49% of architectural dysplasia patients.