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Hyperventilation (HV) is an activation technique performed during clinical practices to trigger epileptiform activities, supporting the neurophysiological evaluation of patients with epilepsy. Although the role of HV has often been questioned, especially in the case of focal epilepsy, no studies have ever assessed how cortical structures respond to such a maneuver via intracranial EEG recordings. This work aims to fill this gap by evaluating the HV effects on the Stereo-EEG (SEEG) signals from a cohort of 10 patients with drug-resistant focal epilepsy. We extracted multiple quantitative metrics from the SEEG signals and compared the results obtained during HV, awake status, non-REM sleep, and seizure onset. Our findings show that the cortical connectivity, estimated via the phase transfer entropy (PTE) algorithm, strongly increases during the HV maneuver, similar to non-REM sleep. The opposite effect is observed during seizure onset, as ictal transitions involve the desynchronization of the brain structures within the epileptogenic zone. We conclude that HV promotes a conductive environment that may facilitate the propagation of epileptiform activities but is not sufficient to trigger seizures in focal epilepsy. [ABSTRACT FROM AUTHOR]

Language lateralization in patients with focal epilepsy frequently diverges from the left-lateralized pattern that prevails in healthy right-handed people, but the mechanistic explanations are still a matter of debate. Here, we debate the complex interaction between focal epilepsy, language lateralization, and functional neuroimaging techniques by introducing the case of a right-handed patient with unaware focal seizures preceded by aphasia, in whom video-EEG and PET examination suggested the presence of focal cortical dysplasia in the right superior temporal gyrus, despite a normal structural MRI. The functional MRI for language was inconclusive, and the neuropsychological evaluation showed mild deficits in language functions. A bilateral stereo-EEG was proposed confirming the right superior temporal gyrus origin of seizures, revealing how ictal aphasia emerged only once seizures propagated to the left superior temporal gyrus and confirming, by cortical mapping, the left lateralization of the posterior language region. Stereo-EEG-guided radiofrequency thermocoagulations of the (right) focal cortical dysplasia not only reduced seizure frequency but led to the normalization of the neuropsychological assessment and the "restoring" of a classical left-lateralized functional MRI pattern of language. This representative case demonstrates that epileptiform activity in the superior temporal gyrus can interfere with the functioning of the contralateral homologous cortex and its associated network. In the case of presurgical evaluation in patients with epilepsy, this interference effect must be carefully taken into consideration. The multimodal language lateralization assessment reported for this patient further suggests the sensitivity of different explorations to this interference effect. Finally, the neuropsychological and functional MRI changes after thermocoagulations provide unique cues on the network pathophysiology of focal cortical dysplasia and the role of diverse techniques in indexing language lateralization in complex scenarios. [ABSTRACT FROM AUTHOR]

The functional anatomy of the anteromesial portion of the temporal lobe and its involvement in epilepsy can be explored by means of intracerebral electrical stimulations. Here, we aimed to expand the knowledge of its physiological and pathophysiological symptoms by conducting the first large‐sample systematic analysis of 1529 electrical stimulations of this anatomical region. We retrospectively analysed all clinical manifestations induced by intracerebral electrical stimulations in 173 patients with drug‐resistant focal epilepsy with at least one electrode implanted in this area. We found that high‐frequency stimulations were more likely to evoke electroclinical manifestations (p <.0001) and also provoked 'false positive' seizures. Multimodal symptoms were associated with EEG electrical modification (after discharge) (p <.0001). Visual symptoms were not associated with after discharge (p =.0002) and were mainly evoked by stimulation of the hippocampus (p =.009) and of the parahippocampal gyrus (p =.0212). 'False positive seizures' can be evoked by stimulation of the hippocampus, parahippocampal gyrus and amygdala, likely due to their intrinsic low epileptogenic threshold. Visual symptoms evoked in the hippocampus and parahippocampal gyrus, without EEG changes, are physiological symptoms and suggest involvement of these areas in the visual ventral stream. Our findings provide meaningful guidance in the interpretation of intracranial EEG studies of the temporal lobe. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Sleep‐related hypermotor epilepsy (SHE), formerly nocturnal frontal lobe epilepsy, is characterized by abrupt and typically sleep‐related seizures with motor patterns of variable complexity and duration. They seizures arise more frequently in the frontal lobe than in the extrafrontal regions but identifying the seizure onset‐zone (SOZ) may be challenging. In this study, we aimed to describe the clinical features of both frontal and extrafrontal SHE, focusing on ictal semiologic patterns in order to increase diagnostic accuracy. Methods: We retrospectively analyzed the clinical features of patients with drug‐resistant SHE seen in our center for epilepsy surgery. Patients were divided into frontal and extrafrontal SHE (temporal, operculoinsular, and posterior SHE). We classified seizure semiology according to four semiology patterns (SPs): elementary motor signs (SP1), unnatural hypermotor movements (SP2), integrated hypermotor movements (SP3), and gestural behaviors with high emotional content (SP4). Early nonmotor manifestations were also assessed. Results: Our case series consisted of 91 frontal SHE and 44 extrafrontal SHE cases. Frontal and extrafrontal SHE shared many features such as young age at onset, high seizure‐frequency rate, high rate of scalp electroencephalography (EEG) and magnetic resonance imaging (MRI) abnormalities, similar histopathologic substrates, and good postsurgical outcome. Within the frontal lobe, SPs were organized in a posteroanterior gradient (SP1‐4) with respect to the SOZ. In temporal SHE, SP1 was rare and SP3‐4 frequent, whereas in operculoinsular and posterior SHE, SP4 was absent. Nonmotor manifestations were frequent (70%) and some could provide valuable localizing information. Significance: Our study shows that the presence of certain SP and nonmotor manifestations may provide helpful information to localize seizure onset in patients with SHE. [ABSTRACT FROM AUTHOR]

Object: To compare the occurrence of surgery-related complications in patients with childhood-onset focal epilepsy operated on in the paediatric or in the adult age. To investigate risk factors for surgery-related complications in the whole cohort, with special attention to age at surgery and severe morbidity.Methods: A cohort of 1282 patients operated on for childhood-onset focal epilepsy was retrospectively analysed. Occurrence of surgery-related complications, including a severely complicated course (SCC: surgical complication requiring reoperation and/or permanent neurological deficit and/or death), was compared between patients operated on in the paediatric age (<16 year-old; 452 cases) and, respectively, in adulthood (≥16 year-old; 830 cases). The whole cohort of patients was also evaluated for risk factors for a SCC.Results: At last contact (median follow-up 98 months), 74.5% of patients were in Engel's class I (78.0% of children and 73.0% of adults). One hundred patients (7.8%) presented a SCC (6.4% for children and 8.6% for adult patients). Postoperative intracranial haemorrhages occurred more frequently in adult cases. At multivariate analysis, increasing age at operation, multilobar surgery, resections in the rolandic/perirolandic and in insulo-opercular regions were independent risk factors for a SCC.Conclusions: Surgery for childhood-onset focal epilepsy provides excellent results on seizures and an acceptable safety profile at any age. Nevertheless, our results suggest that increasing age at surgery is associated with an increase in odds of developing severe surgery-related complications. These findings support the recommendation that children with drug-resistant, symptomatic (or presumed symptomatic) focal epilepsy should be referred for a surgical evaluation as early as possible after seizure onset. [ABSTRACT FROM AUTHOR]

The rationale and the surgical technique of stereo-electroencephalography ( SEEG)-guided radiofrequency thermocoagulation ( RF- TC) in the epileptogenic zone ( EZ) of patients with difficult-to-treat focal epilepsy are described in this article. The application of the technique in pediatric patients is also detailed. Stereotactic ablative procedures by RF- TC have been employed in the treatment of epilepsy since the middle of the last century. This treatment option has gained new popularity in recent decades, mainly because of the availability of modern imaging techniques, which allow accurate targeting of intracerebral epileptogenic structures. SEEG is a powerful tool for identifying the EZ in the most challenging cases of focal epilepsy by recording electrical activity with tailored stereotactic implantation of multilead intracerebral electrodes. The same recording electrodes may be used to place thermocoagulative lesions in the EZ, following the indications provided by intracerebral monitoring. The technical details of SEEG implantation and of SEEG-guided RF- TC are described herein, with special attention to the employment of the procedure in pediatric cases. SEEG-guided RF- TC offers a potential therapeutic option based on robust electroclinical evidence with acceptable risks and costs. The procedure may be performed in patients who, according to SEEG recording, are not eligible for resective surgery, and it may be an alternative to resective surgery in a small subset of operable patients. [ABSTRACT FROM AUTHOR]

Objective In one third of patients with a diagnosis of pharmacoresistant focal epilepsy who are candidates for therapeutic surgery, cerebral areas responsible for seizure generation can be defined exclusively with invasive intracranial recordings. A correct presurgical identification of the epileptogenic zone ( EZ) with intracranial electrodes has a direct impact on postsurgical outcome. We aimed at identifying biomarkers of the EZ based on computer-assisted inspection of intracranial electroencephalography ( EEG). Methods Computer-driven intracranial EEG analysis in the domains of time, frequency, and space was retrospectively applied to a population of 10 patients with focal epilepsy to detect EZ electrophysiologic markers. Next, a prospective study was performed on 14 surgery candidate patients. The stereo- EEG computer-assisted analysis of EZ boundaries performed blind from patients data was compared to that defined with the traditional visual inspection completed by neurophysiologists. Results In the retrospective study, the EZ was characterized by the combined detection of three biomarkers observed at seizure onset: (1) fast activity at 80-120 Hz associated with (2) very slow transient polarizing shift and (3) voltage depression (flattening). Correlations between these indexes were calculated for each seizure. In the prospective study, the quantified analysis based on the three biomarkers confirmed a complete overlap between leads within the EZ identified by expert clinicians. In 2 of 14 patients the proposed biomarkers partially identified the EZ. Significance Our findings demonstrate and validate with a prospective unbiased study the use of three neurophysiologic intracranial EEG parameters as excellent biomarkers of ictogenesis and as reliable indicators of EZ boundaries. [ABSTRACT FROM AUTHOR]

The identification of the epileptogenic zone (EZ) is crucial for planning epilepsy surgery in patients with drug-resistant partial epilepsy. This task may require intracerebral encephalography (EEG) monitoring, the results of which are usually interpreted by visual presurgical inspection. A computer-assisted method for rapidly identifying reproducible ictal patterns based on the analysis of time, frequency, and spatial domains of stereo-EEG (SEEG) signals is described here. A new method for EZ detection was tested on SEEG recordings performed by intracerebral electrodes in eight patients with pharmacoresistant partial epilepsy. SEEG data were exported to a program developed in LabView. Prevalent frequencies during seizure events were evaluated by Fourier transform and further integral algorithms. Different frequencies and the relative powers were simultaneously evaluated in all recording leads. Patterns characterized by specific and prevalent frequencies were identified in a subset of recording sites during both seizure onset and seizure development. Three-dimensional (3D) maps of the measurements obtained from each recording channel were reconstructed on magnetic resonance coordinates to visualize the spatial distribution of the EZ. With this method, the reproducibility of ictal patterns in the same patient was characterized. The boundaries of the EZ identified with this algorithm correlated well with the EZ recognized with the traditional approach (n = 8). The spatial distribution of specific SEEG signals associated with different types of seizures was also analyzed in two patients. We describe a computer-assisted method to acquire information on EZ boundaries and to verify reproducibility of seizure patterns from intracerebral recordings performed in patients with pharmacoresistant partial epilepsies. [ABSTRACT FROM AUTHOR]

Scalp EEG is one of the main tools in the clinical evaluation of epilepsy. In some cases intracranial Interictal Epileptiform Discharges (IEDs) are not visible from the scalp. Recent studies have shown the feasibility of revealing them in the EEG if their timings are extracted from simultaneous intracranial recordings, but their potential for the localization of the epileptogenic zone is not yet well defined. We recorded simultaneous high-density EEG (HD-EEG) and stereo-electroencephalography (SEEG) during interictal periods in 8 patients affected by drug-resistant focal epilepsy. We identified IEDs in the SEEG and systematically analyzed the time-locked signals on the EEG by means of evoked potentials, topographical analysis and Electrical Source Imaging (ESI). The dataset has been standardized and is being publicly shared. Our results showed that IEDs that were not clearly visible at single-trials could be uncovered by averaging, in line with previous reports. They also showed that their topographical voltage distributions matched the position of the SEEG electrode where IEDs had been identified, and that ESI techniques can reconstruct it with an accuracy of ∼2 cm. Finally, the present dataset provides a reference to test the accuracy of different methods and parameters. Our study is the first to systematically compare ESI methods on simultaneously recorded IEDs, and to share a public resource with in-vivo data for their evaluation. Simultaneous HD-EEG and SEEG recordings can unveil hidden IEDs whose origins can be reconstructed using topographical and ESI analyses, but results depend on the selected methods and parameters. • Simultaneous HD-EEG and SEEG recordings allow revealing hidden scalp IEDs. • The scalp topographical voltage distributions are indicative of their putative origin. • ESI can reconstruct their putative origin with an accuracy of ∼ 2 cm. • A comparative analysis of the ESI methods and their parameters has been performed. • The dataset is being shared, providing a common ground to develop and compare methods. [ABSTRACT FROM AUTHOR]

• Hyperkinetic seizure diagnosis may be a challenge even for expert clinicians. • Sleep and type II FCD act independently in favoring hyperkinetic seizures. • Hyperkinetic seizures and complex motor automatisms in preschool children are uncommon. To identify predisposing factors for hyperkinetic seizure occurrence in a representative cohort of surgically treated patients with drug-resistant focal epilepsy. We retrospectively recruited all seizure-free patients after epilepsy surgery with a postoperative follow-up ≥12 months. Patients were classified as presenting with hyperkinetic seizures if at least 2 episodes occurred during their disease history, based on clear-cut anamnestic description and/or video-EEG/stereo-EEG recordings. We performed univariable and multivariable logistic regression models to study the association between the occurrence of hyperkinetic seizures and some predictors. From a pool of 1758 consecutive patients who underwent surgery from 1996 to 2017, we identified 974 seizure-free cases. Considering at least 1-year follow-up, 937 cases were included (511 males, 91 patients with hyperkinetic seizures). Variables significantly associated with an increased risk of hyperkinetic seizure occurrence were (1) presence of epilepsy with sleep-related seizures (SRE) (P < 0.001); (2) histological diagnosis of type II focal cortical dysplasia (FCD) (P < 0.001); (3) resection including the frontal lobe (P = 0.002) (4) duration of epilepsy at surgery (P < 0.001) and (5) high seizure frequency at surgery (weekly: P = 0.02 – daily: P = 0.05). A resection including the occipital lobe reduced the risk of hyperkinetic seizures (P = 0.05). About 63% of patients had hyperkinetic seizure onset before 12 years and it was rarely reported before 5 years of age. Our findings underlie the role of SRE, type II FCD and frontal epileptogenic zone as predictors of hyperkinetic seizure occurrence and highlight an age-dependent effect in favoring hyperkinetic manifestations. [ABSTRACT FROM AUTHOR]

• Non-invasive techniques considered together reached an accuracy of 60–80% in identifying the epileptogenic zone (EZ) compared to SEEG. • The diagnostic yield of non-invasive techniques increased in the subgroup of patients with EZ involving two or more lobes. • EEG-fMRI, MEG or HR-EEG and PET appeared the best combination of techniques in the evaluation of multilobar EZ. We evaluated four imaging techniques, i.e. Electroencephalography (EEG)-functional Magnetic Resonance Imaging (MRI) (EEG-fMRI), High-resolution EEG (HR-EEG), Magnetoencephalography (MEG) and 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (PET), for the identification of the epileptogenic zone (EZ) in 41 patients with negative MRI, candidate to neurosurgery. For each technique, results were compared to the Stereo-EEG. Diagnostic measures were calculated with respect to the post-surgical outcome, either for all the patients (39/41, two patients excluded) and for the subgroup of patients with the EZ involving more than one lobe (20/41). When considered individually, each functional technique showed accuracy values ranging 54,6%–63,2%, having PET, MEG and HR-EEG higher sensitivity, and EEG-fMRI higher specificity. In patients with multilobar epileptogenic zone, functional techniques achieved the best accuracies (up to 80%) when three techniques, including EEG-fMRI, were considered together. The study highlights the accuracy of a combination of functional imaging techniques in the identification of EZ in MRI negative focal epilepsy. The best diagnostic yield was obtained if the combination of PET, MEG (or HR-EEG as alternative), EEG-fMRI were considered together. The functional imaging techniques may improve the presurgical workup of MRI negative focal epilepsy, if epileptogenic zone involves more than one lobe. [ABSTRACT FROM AUTHOR]

Objective Focal Cortical Dysplasias (FCDs) represent a common architectural cortical disorder underlying drug-resistant focal epilepsy. So far, studies aimed at evaluating whether age at surgery is a factor influencing surgical outcome are lacking, so that data on the comparison between patients harboring Type II FCD operated at younger age and those operated at adult age are still scarce. We compared presurgical clinical features and surgical outcomes of patients with histopathologically diagnosed Type II FCD undergoing surgery at an earlier age with those operated after 20 years of age. Methods We retrospectively analyzed 1660 consecutive patients operated at the “Claudio Munari” Epilepsy Surgery Centre. There were 289 patients (17.4%) with a neuropathological diagnosis of Type II FCD. We included two different groups of patients, the first one including patients operated on at less than 6 years, the second sharing the same seizure onset age but with delayed surgery, carried out after the age of 20. Seizure characteristics and, neuropsychological and postoperative seizure outcomes were evaluated by study group. Results Forty patients underwent surgery before the age of 6 and 66 patients after the age of 20. Surgical outcome was favorable in the whole population (72.6% were classified in Engel's Class Ia + Ic), independently from age at surgery. In the children group, 32 patients were classified in Class I, including 30 (75%) children in classes Ia and Ic. In the adult group, 53 belonged to Class I of whom 47 (71%) were in classes Ia and Ic. The percentage of permanent complications, the surgical outcomes, and AED withdrawal did not significantly differ by study group. Conclusion Our results indicate that there is no difference between the groups, suggesting that outcome depends mainly on the histological findings and not on timing of surgery. [ABSTRACT FROM AUTHOR]