Since the original description by Taylor, the term focal cortical dysplasia has been used to refer to a wide range of alterations of the cortical mantle. More recently, these conditions have been described from neuroimaging, neuropathological and genetic standpoints, generating several classifications. It is widely recognized that these classifications are unsatisfactory. We propose a simplified classification of focal cortical dysplasias based on easily recognized neuropathological characteristics. We retrospectively re-examined histological sections of cortex from 52 of 224 (23%) patients operated on for drug-resistant partial epilepsy in which cortical dysplasia was present but not associated with other brain pathologies except hippocampal sclerosis. Three subgroups were identified: (i) architectural dysplasia (31 patients) characterized by abnormal cortical lamination and ectopic neurones in white matter; (ii) cytoarchitectural dysplasia (six patients) characterized by giant neurofilament-enriched neurones in addition to altered cortical lamination; and (iii) Taylor-type cortical dysplasia (15 patients) with giant dysmorphic neurones and balloon cells (all but two patients) associated with cortical laminar disruption. The patients with architectural dysplasia had lower seizure frequency than those with cytoarchitectural and Taylor-type dysplasia, and the epileptogenic zone was mainly in the temporal lobe. In patients with Taylor-type dysplasia, the epileptogenic zone was mainly extratemporal, and interictal stereo-EEG was distinctive. MRI was unrevealing in 34% of patients, but distinctive signal alterations characterized most patients with Taylor-type dysplasia, while focal hypoplasia with MRI abnormalities was found in architectural dysplasia. Patients with Taylor-type dysplasia had the best outcome, with 75% seizure-free (Engel class Ia) after at least a year of follow-up compared with 50% of cytoarchitectural dysplasia and 43% of architectural dysplasia patients seizure-free. This three-category classification is based on easily recognized histopathological characteristics and avoids complicated terminology, while the distinctive ensemble of other characteristics defines clinically homogeneous groups.

The cingulate cortex is a mosaic of different anatomical fields, whose functional characterization is still a matter of debate. In humans, one method that may provide useful insights on the role of the different cingulate regions, and to tackle the issue of the functional differences between its anterior, middle and posterior subsectors, is intracortical electrical stimulation. While previous reports showed that a variety of integrated behaviours could be elicited by stimulating the midcingulate cortex, little is known about the effects of the electrical stimulation of anterior and posterior cingulate regions. Moreover, the internal arrangement of different behaviours within the midcingulate cortex is still unknown. In the present study, we extended previous stimulation studies by retrospectively analysing all the clinical manifestations induced by intracerebral high frequency electrical stimulation (50 Hz, pulse width: 1 ms, 5 s, current intensity: average intensity of 2.7 ± 0.7 mA, biphasic) of the entire cingulate cortex in a cohort of 329 drug-resistant epileptic patients (1789 stimulation sites) undergoing stereo-electroencephalography for a presurgical evaluation. The large number of patients, on one hand, and the accurate multimodal image-based localization of stereo-electroencephalography electrodes, on the other hand, allowed us to assign specific functional properties to modern anatomical subdivisions of the cingulate cortex. Behavioural or subjective responses were elicited from the 32.3% of all cingulate sites, mainly located in the pregenual and midcingulate regions. We found clear functional differences between the pregenual part of the cingulate cortex, hosting the majority of emotional, interoceptive and autonomic responses, and the anterior midcingulate sector, controlling the majority of all complex motor behaviours. Particularly interesting was the 'actotopic' organization of the anterior midcingulate sector, arranged along the ventro-dorsal axis: (i) whole-body behaviours directed to the extra-personal space, such as getting-up impulses, were elicited ventrally, close to the corpus callosum; (ii) hand actions in the peripersonal space were evoked by the stimulation of the intermediate position; and (iii) body-directed actions were induced by the stimulation of the dorsal branch of the cingulate sulcus. The caudal part of the midcingulate cortex and the posterior cingulate cortex were, in contrast, poorly excitable, and mainly devoted to sensory modalities. In particular, the caudal part of the midcingulate cortex hosted the majority of vestibular responses, while posterior cingulate cortex was the principal recipient of visual effects. We will discuss our data in the light of current controversies on the role of the cingulate cortex in cognition and emotion.

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.

Running title: Wearable multimodal motor seizure detectors Onorati et al. 2 Summary Objective:New devices are needed for monitoring seizures, especially those associated with sudden unexpected death in epilepsy (SUDEP). They must be unobtrusive, automated and provide false alarm rates bearable in everyday life. This study quantifies the performance of new multimodal wrist-worn convulsive seizure detectors. Methods:Hand-annotated video-electroencephalography seizure events were collected from 69 patients at 6 clinical sites. Three different wristbands were used to record electrodermal activity (EDA) and accelerometer (ACM) signals, obtaining 5,928 hours of data, including 55 convulsive epileptic seizures (6 focal tonic-clonic seizures and 49 focal-to-bilateral-tonicclonic seizures) from 22 patients. Recordings were analyzed off-line to train and test two new machine learning classifiers and a published EDA and ACM-based classifier. Moreover, wristband data were analyzed to estimate seizure-motion duration and autonomic responses. Results:The two novel classifiers consistently outperformed the previous detector. The most efficient (Classifier III) yielded sensitivity of 94.55%, and false alarm rate (FAR) of 0.2 events/day.No nocturnal seizures were missed. Most patients had less than 1 false alarm every 4 days with FAR below their seizure frequency. When increasing the sensitivity to 100% (no missed seizures) the FAR is up to 13 times lower than the previous detector. Furthermore, all detections occurred before the seizure ended, providing reasonable latency (median: 29.3 s, range: 14.8-151 s). Automatically estimated seizure durations were correlated with true durations, enabling reliable annotations. Finally, EDA measurements confirmed the presence of post-ictal autonomic dysfunction, exhibiting a significant rise in 73% of the convulsive seizures. Onorati et al. 3 Significance:The proposed multimodal wrist-worn convulsive seizure detectors provide seizure counts that are more accurate than previous automated detectors and typical patient self-reports, while maintaining a tolerable FAR for ambulatory monitoring. Furthermore, the multimodal system provides an objective description of motor behaviour and autonomic dysfunction, aimed at enriching seizure characterization, with potential utility for SUDEP warning.

aBBreViatiONS EEG = electroencephalography; EZ = epileptogenic zone; FCD = focal cortical dysplasia; MTLE = mesial temporal lobe epilepsy; RF-TC = radiofrequency thermocoagulation; SEEG = stereoelectroencephalography. SuBmitted August 28, 2014. accepted December 8, 2014. iNclude wheN citiNg Published online June 19, 2015; DOI: 10.3171/2014.12.JNS141968. diSclOSure Dr. Cardinale is a consultant for Renishaw Mayfield SA, the manufacturer of Neuromate, and a former consultant for Medtronic, the manufacturer of the O-arm device. The other authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. OBJect Radiofrequency thermocoagulation (RF-TC) of presumed epileptogenic lesions and/or structures has gained new popularity as a treatment option for drug-resistant focal epilepsy, mainly in patients with mesial temporal lobe epilepsy. The role of this minimally invasive procedure in more complex cases of drug-resistant epilepsy, which may require intracranial electroencephalographic evaluation, has not been fully assessed. This retrospective study reports on a case series of patients with particularly complex focal epilepsy who underwent stereoelectroencephalography (SEEG) evaluation with stereotactically implanted multicontact intracerebral electrodes for the detailed identification of the epileptogenic zone (EZ) and who received RF-TC in their supposed EZ (according to SEEG findings). methOdS Eighty-nine patients (49 male and 40 female; age range 2-49 years) who underwent SEEG evaluation and subsequent RF-TC of the presumed EZ at the authors' institution between January 2008 and December 2013 were selected. Brain MRI revealed structural abnormalities in 43 cases and no lesions in 46 cases. After SEEG, 67 patients were judged suitable for resective surgery (Group 1), whereas surgery was excluded for 22 patients (Group 2). Thermocoagulation was performed in each of these patients by using the previously implanted multicontact recording electrodes and delivering RF-generated currents to adjacent electrode contacts. reSultS The mean number of TC sites per patient was 10.6 ± 7.2 (range 1-33). Sustained seizure freedom occurred after TC in 16 patients (18.0%) (13 in Group 1 and 3 in Group 2). A sustained worthwhile improvement was reported by 9 additional patients (10.1%) (3 in Group 1 and 6 in Group 2). As a whole, 25 patients (28.1%) exhibited a persistent significant improvement in their seizures. More favorable results were observed in patients with nodular heterotopy (p = 0.0001389), those with a lesion found on MRI (not significant), and those with hippocampal sclerosis (not significant). Other variables significantly correlated to seizure freedom were the patient's age (p = 0.02885) and number of intralesional TC sites (p = 0.0271). The patients in Group 1 who did not benefit at all (21 patients) or who experienced only a transient benefit (30 patients) from TC underwent microsurgical resection of their EZ. Thermocoagulation was followed by se...