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Objective: Vagal Nerve Stimulation (VNS) is an effective treatment for Drug-Resistant (DR) epilepsy. Albeit the corroborated effectiveness of VNS, little is known about how VNS works. We aim to leverage quantitative Electroencephalography (qEEG) to study how the brain responds to VNS cycles., Methods: Eighteen subjects with DR epilepsy were enrolled in our study. 64-channel EEG was recorded during VNS stimulation. Periods of stimulation (VNS), preceding (preVNS) and following stimulation (postVNS) were identified via an electrode placed on the stimulator. We used qEEG analysis to assess changes in spectral and network activity that characterize these conditions. Graph theory metrics were used to calculate differences in network connectivity., Results: No differences were found in spectral activity between preVNS, VNS, and postVNS. Graph theory showed consistent changes in network organization expressed by Small World Index (SWI), Betweenness Centrality (BtwC), and Global Efficiency (gE). These changes were most significant in the slow EEG bands., Conclusions: In DR epilepsy, VNS has a significant effect on brain network activity, as assessed by EEG connectivity, acting on widespread network distribution rather than band-power., Significance: Our findings support the hypothesis that VNS acts on epilepsy by influencing diffuse network connectivity in the brain., (Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Several types of palliative surgery to treat drug-resistant epilepsy (DRE) have been reported, but the evidence that is available is insufficient to help physicians redirect patients with DRE to the most appropriate kind of surgery., Methods: A systematic search in the PubMed and Scopus databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to compare different clinical features, outcomes, and complications of adult patients submitted to callosotomy, vagal nerve stimulation, multiple subpial transections, deep brain stimulation, or responsive neurostimulation., Results: After 3447 articles were screened, 36 studies were selected, including the data of 1628 patients: 76 were treated with callosotomy, 659 were treated with vagal nerve stimulation, 416 were treated with deep brain stimulation, and 477 were treated with responsive neurostimulation. No studies including patients treated with multiple subpial transections met the inclusion criteria. The global weighted average seizure frequency reduction was 50.23%, and the global responder rate was 52.12%. There were significant differences among the palliative surgical procedures in term of clinical features of patients and epilepsy, seizure frequency reduction, and percentage of responders. Complications were differently distributed as well., Conclusions: Our analysis highlights the necessity of prospective studies, possibly randomized controlled trials, to compare different forms of palliative epilepsy surgery. Moreover, by identifying the outcome predictors associated with each technique, the best responder may be profiled for each procedure., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To analyze relationships between CD34 expression and several demographic, clinical, and pathologic features in patients with histopathologic evidence of low-grade epilepsy-associated tumors who underwent epilepsy surgery., Methods: A retrospective study enrolling 187 patients with low-grade epilepsy-associated tumors who underwent surgery between January 2009 and June 2015 at 8 Italian epilepsy surgery centers was conducted. All cases were histologically diagnosed according to the World Health Organization classification of central nervous system tumors. Univariate and multivariate analyses were performed to identify variables associated with CD34 expression., Results: Of 187 patients, 95 (50.8%) were CD34 positive. Tumor type and duration of epilepsy were independently associated with CD34 expression on multivariate analysis. Ganglioglioma and pleomorphic xanthoastrocytoma were the histologic types with the strongest association with CD34 positivity with an odds ratio of 9.2 and 10.4, respectively, compared with dysembryoplastic neuroepithelial tumors. Patients with a duration of epilepsy >10 years had a significantly greater likelihood to show CD34 expression, with an odds ratio of 2.8 compared with patients with a duration of epilepsy <2 years. On univariate analysis, CD34 expression appeared to be significantly related to older age at surgery, higher antiepileptic drug intake, and female sex., Conclusions: CD34 expression holds promise as a useful biomolecular marker for patients with low-grade epilepsy-associated tumors with evidence of a link with clinicopathologic features. This study confirmed the association between CD34 expression and tumor type and demonstrated a significantly higher probability of CD34 expression in patients with longer duration of epilepsy, independent of histology., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To analyse waveforms, latencies and amplitudes of Median Nerve (MN) SEPs recorded by stereotactically electrodes implanted in the SMA of 14 epileptic patients (9 in pre-SMA,3 in SMA-proper, 2 in both) in order to evaluate which short and middle-latency SEPs are generated in this area and which could be the physiological relevance of these responses., Methods: Short and middle-latency MN SEPs were recorded by chronically implanted electrodes in the fronto-temporal cortex and in particular in the mesial frontal region of 14 drug-resistant epileptic patients. MN stimulations of 100 micros were delivered by skin electrodes at the wrist; stimulus intensity was adjusted slightly above the motor threshold., Results: The main result of this study is that middle-latency SEPs were originated in pre-SMA but not in SMA-proper as demonstrated by both referential and bipolar recordings. In particular off-line computed bipolar traces between neighbouring contacts implanted in the pre-SMA and in the frontal external regions showed a phase reversal at the deepest contacts located in pre-SMA. Conversely, bipolar recordings between neighbouring contacts implanted in the SMA-proper and in the frontal external regions showed inversion recovery at more superficial contacts, implanted in area 6. Finally, we confirmed that no short-latency MN SEP (and in particular the N30) is originated in the whole SMA., Conclusions: Among premotor areas, somatosensory inputs seem to reach pre-SMA and area 6 but not SMA-proper., Significance: This study assessed that no scalp SEP in the first 100 ms after MN stimulus could be generated in SMA-proper.

Purpose: To describe repetitive movements of the right arm possibly originating from the ipsilateral SMA area in two drug-resistant epileptic patients., Methods: Two epileptic patients (one female, one male, 35 and 36 years old, respectively) were submitted to pre-surgical evaluation including history, neurological examination, long-term video-EEG monitoring, interictal and ictal SPET, MRI and fMRI, neuropsychological assessment. Invasive recordings (stereoelectroencephalography) were also performed., Results: In both patients ictal semiology was characterized by very stereotyped repetitive right arm movements, i.e. tapping towards the thorax (movement rate of 6-7 Hz and 3-4 Hz for the two subjects, respectively). Seizures in the first patient, whose epilepsy was cryptogenetic, originated from the right pre-SMA area, which was surgically removed. She is seizure free 2 years after the operation. In the second patient, in whom a right pre-frontal post-abscess porencephaly was disclosed, the epileptogenic zone included the lesion and surrounding areas, while the SMA area was involved less consistently., Conclusions: Even if, according to literature, SMA epilepsy is predominantly characterized by postural manifestations, ipsilateral repetitive movements could be a relevant sign in this kind of epilepsy, as showed in our first patient. The presence of similar semiology in the second patient, might suggest that the symptomatogenic zone involved SMA area.

Objective: To identify low and high-frequency median nerve (MN) somatosensory evoked potential (SEP) generators by means of chronically implanted electrodes in the parietal lobe (SI and neighbouring areas) of two epileptic patients., Methods: Wide-pass short-latency and long-latency SEPs to electrical MN stimulation were recorded in two epileptic patients by stereotactically chronically implanted electrodes in the parietal lobe (SI and neighbouring areas). To study high-frequency responses (HFOs) an off-line digital filtering of depth short-latency SEPs was performed (500-800 Hz, 24 dB roll-off). Spectral analysis was performed by fast Fourier transform., Results: In both patients we recorded a N20/P30 potential followed by a biphasic N50/P70 response. A little negative response in the 100 ms latency range was the last detectable wide-pass SEP in both patients. Two HFOs components (called iP1 and iP2) were detected by mere visual analysis and spectral analysis, and were supposed to be originated within the parietal cortex., Conclusions: This was the very first study that recorded wide bandpass and high frequency SEPs by electrodes, exploring both the lateral and the mesial part of the parietal lobe and particularly that of the post-central gyrus.

Objective: To investigate the possible contribution of the primary somatosensory area (SI) to pain sensation., Methods: Depth recordings of CO2 laser evoked potentials (LEPs) and somatosensory evoked potentials (SEPs) were performed in an epileptic patient with a stereotactically implanted electrode (Talairach coordinates y=-23, z=40) that passed about 10 mm below the hand representation in her left SI area, as assessed by the source of the N20 SEP component., Results: The intracerebral electrode was able to record the N20 SEP component after non-painful electrical stimulation of her right median nerve. The N20 potential showed a phase reversal in the bipolar montage (at about 31 mm from the midline), which confirms that the electrode was located near its generator in area 3b. In contrast, no reliable response was recorded from the SI electrode after painful CO2 laser stimulation of the right hand. An N2-P2 response was evoked at the vertex electrode (Cz), thus demonstrating the effectiveness of the delivered CO2 laser stimuli., Conclusions: Since the N20 SEP component originates from the anterior bank of the post-central gyrus (area 3b), our result suggests that this part of SI does not participate in LEP generation. In fact, the previously published LEP sources in the SI area estimated from scalp recordings are about 10-17 mm posterior of the electrode in our patient, suggesting that they are more likely located in area 1, 2 or posterior parietal cortex.

Thirteen patients suffering from severe partial epilepsy and potential candidates for surgical treatment were investigated with stereotactically implanted intracerebral electrodes during nocturnal physiological sleep. The recorded electrocerebral activity was automatically analyzed to gain information on interictal epileptic events during wakefulness and the phases of sleep. The interictal epileptic activity shows: (1) great variability in the different subjects, and intra-individually, variability according to the explored cerebral regions; (2) is not influenced by the location of the recorded epileptic events; and (3) is affected by the local level of epileptogenicity. The latter was determined by the assessment of the capacity to give origin to ictal discharges and the disappearance of seizures following surgical removal. The interictal rate of spiking from the most epileptogenic cerebral zone is characterized by a relative stability during the night and by a relatively high degree during REM sleep.

Cerebral electrical activity was recorded through chronic stereotactically implanted electrodes in 19 epileptic patients suffering from different types of severe and medically refractory partial seizures and who were considered for surgical treatment. 213 brain sites, in all cerebral lobes, in neocortical as well as in archicortical structures, were explored. The behaviour of the interictal spiking across wakefulness and nocturnal physiological sleep was analysed, using automatic elaboration. (i) Spike rate is affected by the occurrence of sleep and by the passage from one sleep phase to another. The degree and direction of the phenomenon differ remarkably in the various patients and, in the same patient, in the different cerebral sites explored. Generally, interictal spiking increases at the beginning of sleep, reaches its maximum during the deep non-REM phases and returns to a level slightly lower than that in wakefulness during REM. (ii) The nocturnal spike rate is hardly influenced by spike location. In most cases, however, the variations recorded during sleep are more significant in the frontal regions than elsewhere. (iii) Spike rate across wakefulness and sleep is affected by the local level of epileptogenicity: spiking variations are less in the most epileptogenic cerebral zone (identified by the origin of the seizure discharges and by the disappearance of seizures following its surgical removal) than elsewhere. The physio-pathological meaning and the diagnostic value of these findings, and particularly of the peculiar stability or autonomy of the electrical epileptic activity of the most epileptogenic cerebral zone, is discussed.