Afterdischarge Research Articles

New stimulation procedures for language mapping in stereo-EEG.

Cortical intracerebral electrical stimulation is an important tool for language mapping in the presurgical work-up of patients with drug-resistant focal epilepsy. Language mapping with stereo-electroencephalography (EEG) is usually performed by high-frequency stimulations (HFS: 50 Hz), whereas low-frequency stimulations (LFS: 1 Hz) are usually considered useful for primary cortices mapping. Little is known in literature about "intermediate" frequencies (IFS: 6-15 Hz). Our objective is to explore the clinical usefulness of IFS in language mapping and identify factors, beyond the electrical parameters, that impact the mapping. We studied 23 patients submitted to stereo-EEG for presurgical evaluation. Language mapping was performed in the anterior, posterior and/or basal language region of the dominant hemisphere for language. We included all contact positions within these regions stimulated by HFS (50 Hz, 5 s, 1-3 mA) and IFS (6-15 Hz, 15 s, 5 mA). We compared the capability of both stimulation methods to induce a language deficit without afterdischarges (ADs), and we analyzed factors related to clinical examination, region, and stimulation technique by multivariate analysis. A total of 211 stimulations (98 HFS, 113 IFS) in 70 cortical sites within the anterior (84 stimulations), posterior (137), and basal language region (60) were included. IFS induced more frequently language deficits not associated to AD compared to HFS (37.1% vs 25.7%, p = .0043), whereas HFS provoked more diffuse AD (34.7% vs 15.0%, p = .001). Investigating multiple language functions increased the probability of revealing a deficit (odds ratio [OR] 3.16, p = .0016), independently of the stimulation method. IFS are valuable for language mapping, thereby improving the probability of inducing a clinical deficit not accompanied by an AD. The completeness of the clinical examination independently affects the sensitivity of the mapping. IFS are a new tool with potential usefulness for the cortical mapping of other associative cortical regions.

Specific afterdischarge properties can enhance the clinical utility of electrical stimulation mapping during intracranial monitoring

ObjectiveExtraoperative electrical cortical stimulation (ECS) facilitates defining the seizure onset zone (SOZ) and eloquent cortex. The clinical relevance of stimulation-induced afterdischarges (ADs) is not well defined. MethodsFifty-five patients who underwent intracranial electroencephalogram evaluations with ECS were retrospectively identified. ADs were identified in these recordings and categorized by pattern, location, and association with stimulation-induced seizures. ResultsADs were generated in 1774/9285 (19%) trials. Rhythmic spikes and irregular ADs within the stimulated bipolar contact pair were predictive of location within the SOZ compared to non-epileptogenic/non-irritative cortex (rhythmic spikes OR 2.24, p = 0.0098; irregular OR 1.39; p = 0.013). ADs immediately preceding stimulated seizures occurred at lower stimulation intensity thresholds compared to other stimulations (mean 2.94 ± 0.28 mA vs. 4.16 ± 0.05 mA respectively; p = 0.0068). ConclusionsChanges in AD properties can provide clinically relevant data in extraoperative stimulation mapping. SignificanceAlthough not exclusive to the SOZ, the generation of rhythmic spikes may suggest that a stimulation location is within the SOZ, while decreased stimulation intensity thresholds eliciting ADs may alert clinicians to a heightened probability of seizure generation with subsequent stimulation.

Adenosine A1 Receptors Participate in Excitability Changes after Cortical Epileptic Afterdischarges in Immature Rats.

Background: Postictal refractoriness, i.e., the inability to elicit a new epileptic seizure immediately after the first one, is present in mature animals. Immature rats did not exhibit this refractoriness, and it is replaced by postictal potentiation. In addition to the immediate postictal potentiation, there is a delayed potentiation present at both ages. These phenomena were studied using cortical epileptic afterdischarges as a model. Objective: We aimed to analyze participation of adenosine A1 receptors in postictal potentiation and depression. Methods: Adenosine A1 receptors were studied by means of Western blotting in the cerebral cortex with a focus on the age groups studied electrophysiologically. Stimulation and recording electrodes were implanted epidurally in 12- and 25-day-old rats. The first stimulation always induced conditioning epileptic afterdischarge (AD), and 1 min after its end, the stimulation was repeated to elicit the second, testing AD. Then, the drugs were administered and paired stimulations were repeated 10 min later. A selective agonist CCPA (0.5 and 1 mg/kg i.p.) and a selective antagonist DPCPX (0.1, 0.5 and 1 mg/kg i.p.) were used to examine the possible participation of adenosine A1 receptors. Results: Control younger animals exhibited potentiation of the testing AD and a moderate increase in both conditioning and testing ADs after an injection of saline. The A1 receptor agonist CCPA shortened both post-drug ADs, and neither potentiation was present. The administration of an antagonist DPCPX resulted in marked prolongation of the conditioning AD (delayed potentiation), and the second testing AD was shorter than the post-drug conditioning AD, i.e., there was no longer immediate potentiation of ADs. To eliminate effects of the solvent dimethylsulfoxide, we added experiments with DPCPX suspended with the help of Tween 80. The results were similar, only the prolongation of ADs was not as large, and the testing ADs were significantly depressed. The older control group exhibited a nearly complete suppression of the first testing AD. There was no significant change in the conditioning and testing ADs after CCPA (delayed potentiation was blocked). Both groups of DPCPX-treated rats (with DMSO or Tween) exhibited significant augmentation of delayed potentiation but no significant difference in the immediate depression. Adenosine A1 receptors were present in the cerebral cortex of both age groups, and their quantity was higher in 12- than in 25-day-old animals. Conclusions: An agonist of the A1 receptor CCPA suppressed both types of postictal potentiation in 12-day-old rats, whereas the A1 antagonist DPCPX suppressed immediate potentiation but markedly augmented the delayed one. Immediate postictal refractoriness in 25-day-old rats was only moderately (non-significantly) affected; meanwhile, the delayed potentiation was strongly augmented.

Enhanced sensitivity of electrocorticography during awake craniotomy using a novel circular grid electrode.

Awake craniotomy with intraoperative functional brain mapping (FBM) bedside neurological testing is an important technique used to optimize resective brain surgeries near eloquent cortex. Awake craniotomy performed with electrocorticography (ECoG) and direct electrical stimulation (DES) for FBM can delineate eloquent cortex from lesions and epileptogenic regions. However, current electrode technology demonstrates spatial limitations. Our group has developed a novel circular grid with the goal of improving spatial recording of ECoG to enhance detection of ictal and interictal activity. This retrospective study was approved by the institutional review board at Mayo Clinic Florida. We analyzed patients undergoing awake craniotomy with ECoG and DES and compared ECoG data obtained using the 22 contact circular grid to standard 6 contact strip electrode. We included 144 cases of awake craniotomy with ECoG, 73 using circular grid and 71 with strip electrode. No significant differences were seen regarding preoperative clinical and demographic data, duration of ECoG recording (p = 0.676) and use of DES (p = 0.926). Circular grid was more sensitive in detecting periodic focal epileptiform discharges (PFEDs) (p = 0.004), PFEDs plus (p = 0.032), afterdischarges (ADs) per case (p = 0.022) at lower minimum (p = 0.012) and maximum (p < 0.0012) intensity stimulation, and seizures (p = 0.048). PFEDs (p < 0.001), PFEDs plus (p < 0.001), and HFOs (p < 0.001) but not ADs (p = 0.255) predicted electrographic seizures. We demonstrate higher sensitivity in detecting ictal and interictal activity on ECoG during awake craniotomy with a novel circular grid compared to strip electrode, likely due to better spatial sampling during ECoG. We also found association between PFEDs and intraoperative seizures.

After-discharge activity as a basis to change intraoperative mapping protocol for functionally significant brain areas

Background. After-discharge (AD) activity is a pattern that differs from background corticography, represented by rhythmic stereotypical slow waves and/or repetitive spike discharges with ≥1 Hz frequency, recorded after cessation of electrical stimulation and lasting for more than 2 seconds. Despite the accumulated experience in the field of intraoperative neuromonitoring, there is no unified protocol for high-frequency stimulation of cortical functional areas (FAs) upon the AD event.Objective: to demonstrate a need to change the intraoperative FAs mapping protocol in patients with brain tumor on awakening in cases of AD recording.Material and methods. Two clinical cases of awake surgical functional mapping followed by resection of the brain tumor are presented. Multimodal monitoring included high-frequency stimulation according to the approved intrahospital protocol with maximum stimulation force of auditory-speech zones of 2.5 mA, electrocorticography, and subcortical dynamic mapping.Results. In the first case, AD was registered while FAs mapping in a patient with a history of one epileptic seizure, upon reaching the maximum stimulation force of 2.5 mA, that was replaced by recording focal epileptiform activity with the following evolution to ictal generalized event and development of intraoperative convulsive seizure. In the second patient with a history of recurrent epileptic seizures, AD with spatiotemporal evolution of the pattern development of clinical ictal event was registered with stimulation at 2.5 mA. In both cases, the appearance of AD required to change mapping protocol with a stepwise decrease in stimulus strength to obtain cortical FAs data.Conclusion. Registration of AD is the basis for changing the protocol of high-frequency cortical stimulation in surgical treatment of brain tumor FAs.

Comparing electrical stimulation functional mapping with subdural electrodes and stereoelectroencephalography.

Electrical stimulation mapping (ESM) is the clinical standard for functional localization with subdural electrodes (SDE). As stereoelectroencephalography (SEEG) has emerged as an alternative option, we compared functional responses, afterdischarges (ADs), and unwanted ESM-induced seizures (EISs) between the two electrode types. Incidence and current thresholds for functional responses (sensory, motor, speech/language), ADs, and EISs were compared between SDE and SEEG using mixed models incorporating relevant covariates. We identified 67 SEEG ESM and 106 SDE ESM patients (7207 and 4980 stimulated contacts, respectively). We found similar incidence of language and motor responses between electrode types; however, more SEEG patients reported sensory responses. ADs and EISs occurred less commonly with SEEG than SDE. Current thresholds for language, face motor, and upper extremity (UE) motor responses and EIS significantly decreased with age. However, they were not affected by electrode type, premedication, or dominant hemispheric stimulation. AD thresholds were higher with SEEG than with SDE. For SEEG ESM, language thresholds remained below AD thresholds up to 26 years of age, whereas this relationship was inverse for SDE. Also, face and UE motor thresholds fell below AD thresholds at earlier ages for SEEG than SDE. AD and EIS thresholds were not affected by premedication. SEEG and SDE have clinically relevant differences for functional brain mapping with electrical stimulation. Although evaluation of language and motor regions is comparable between SEEG and SDE, SEEG offers a higher likelihood of identifying sensory areas. A lower incidence of ADs and EISs, and a favorable relationship between functional and AD thresholds suggest superior safety and neurophysiologic validity for SEEG ESM than SDE ESM.

Impact of intraoperative direct cortical stimulation dynamics on perioperative seizures and afterdischarge frequency in patients undergoing awake craniotomy.

Intraoperative stimulation is used as a crucial adjunct in neurosurgical oncology, allowing for greater extent of resection while minimizing morbidity. However, limited data exist regarding the impact of cortical stimulation on the frequency of perioperative seizures in these patients. A retrospective chart review of patients undergoing awake craniotomy with electrocorticography data by a single surgeon at the authors' institution between 2013 and 2020 was conducted. Eighty-three patients were identified, and electrocorticography, stimulation, and afterdischarge (AD)/seizure data were collected and analyzed. Stimulation characteristics (number, amplitude, density [stimulations per minute], composite score [amplitude × density], total and average stimulation duration, and number of positive stimulation sites) were analyzed for association with intraoperative seizures (ISs), ADs, and postoperative clinical seizures. Total stimulation duration (p = 0.005), average stimulation duration (p = 0.010), and number of stimulations (p = 0.020) were found to significantly impact AD incidence. A total stimulation duration of more than 145 seconds (p = 0.04) and more than 60 total stimulations (p = 0.03) resulted in significantly higher rates of ADs. The total number of positive stimulation sites was associated with increased IS (p = 0.048). Lesions located within the insula (p = 0.027) were associated with increased incidence of ADs. Patients undergoing repeat awake craniotomy were more likely to experience IS (p = 0.013). Preoperative antiepileptic drug use, seizure history, and number of prior resections of any type showed no impact on the outcomes considered. The charge transferred to the cortex per second during mapping was significantly higher in the 10 seconds leading to AD than at any other time point examined in patients experiencing ADs, and was significantly higher than any time point in patients not experiencing ADs or ISs. Although the rate of transfer for patients experiencing ISs was highest in the 10 seconds prior to the seizure, it was not significantly different from those who did not experience an AD or IS. The data suggest that intraoperative cortical stimulation is a safe and effective technique in maximizing extent of resection while minimizing neurological morbidity in patients undergoing awake craniotomies, and that surgeons may avoid ADs and ISs by minimizing duration and total number of stimulations and by decreasing the overall charge transferred to the cortex during mapping procedures.

Effect of low frequency stimulation of olfactory bulb on seizure severity, learning, and memory in kindled rats

Low frequency deep brain electrical stimulation (LFS) is a potential therapeutic strategy to control seizures in epilepsy patients. Given the functional connection of the olfactory bulb with the hippocampal formation, in this study the effect of applying LFS in the olfactory bulb on seizure severity, and learning and memory was investigated in hippocampal kindling. In male Wistar rats (250–300 g), a tripolar electrode was inserted in the CA1 region of the right hippocampus to apply kindling stimulations and record the afterdischarges (ADs). Two bipolar electrodes were also inserted bilaterally into the olfactory bulbs for applying LFS. In the kindled group, the animals received daily kindling stimulations to produce stage 5 seizures for three consecutive days. In one group of subjects, LFS was administered 2–3 min after the last kindling stimulation. Within this group, subjects were divided into two subgroups: one subgroup received two and the other subgroup received four packages of LFS protocol. Obtained data showed that bilateral LFS application to the left and right olfactory bulb reduced seizure severity. Among the protocols, applying four packages of LFS had a greater anticonvulsant effect compared to applying two packages LFS. Applying LFS in the olfactory bulb of kindled subject restored performance on measures that test short- and long-term memory – the Y maze and Morris water maze test – and applying four packages of LFS was more effective than two. These results indicated that applying LFS to the olfactory bulb had anticonvulsant effects and ameliorated the seizure-induced impairment of working and spatial memory. These effects appear to be depended on the number of applied LFS and were greater by increasing the number of LFS.

Comprehensive phenotyping of cutaneous afferents reveals early-onset alterations in nociceptor response properties, release of CGRP, and hindpaw edema following spinal cord injury

Spinal cord injury (SCI) is a complex syndrome that has profound effects on patient well-being, including the development of medically-resistant chronic pain. The mechanisms underlying SCI pain have been the subject of thorough investigation but remain poorly understood. While the majority of the research has focused on changes occurring within and surrounding the site of injury in the spinal cord, there is now a consensus that alterations within the peripheral nervous system, namely sensitization of nociceptors, contribute to the development and maintenance of chronic SCI pain. Using an ex vivo skin/nerve/DRG/spinal cord preparation to characterize afferent response properties following SCI, we found that SCI increased mechanical and thermal responding, as well as the incidence of spontaneous activity (SA) and afterdischarge (AD), in below-level C-fiber nociceptors 24 hr following injury relative to naïve controls. Interestingly, the distribution of nociceptors that exhibit SA and AD are not identical, and the development of SA was observed more frequently in nociceptors with low heat thresholds, while AD was found more frequently in nociceptors with high heat thresholds. We also found that SCI resulted in hindpaw edema and elevated cutaneous calcitonin gene-related peptide (CGRP) concentration that were not observed in naïve mice. These results suggest that SCI causes a rapidly developing nociceptor sensitization and peripheral inflammation that may contribute to the early emergence and persistence of chronic SCI pain.

P.097 After-discharges and presurgical cortical stimulation in stereo-encephalography in the study of drug-resistant epilepsy

Background: Background: Cortical stimulation (CS) as a part of presurgical investigations in patients undergoing implantation of depth electrodes (SEEG) is a growing practice in some Comprehensive Epilepsy Centers. After-discharges (AD) are useful to determine epileptogenic tissue within or outside the epileptogenic network. Classification of afterdischarges was proposed by Blume using subdural recordings(1); its utility in SEEG is unknown. Methods: Methods: Single center, retrospective study that included patients with SEEG that underwent CS in the Epilepsy Monitoring Unit. Demographic characteristics were explored and Blume’s proposed AD classification was used to determine whether or not the CS changed surgical outcomes. Results: Results: From January 2015 to June 2021, a total of 177 patients were implanted with SEEG and analyzed. 95 patients had CS and 91 had AD. Morphologies found were: Rhythmic waves in 4 (0.04%), Rhythmic waves evolving into spikes in18 (19%), Polyspike bursts in 14 (15%), Spike-waves in 28 (30%), and sequential spikes in 18 (19%). 12/14 (86%) patients with Spike-waves had Engel I outcome; Engel class IV patients were more likely to have an evolution of morphology and frequency of ADs in 3 patients(75%). Conclusions: Conclusions: The most frequent morphology of ADs seen was spike-waves. AD morphology and duration may predict post-operative seizure outcomes.

Increased Hippocampal Afterdischarge Threshold in Ketogenic Diet is Accompanied by Enhanced Kynurenine Pathway Activity.

The efficacy of a ketogenic diet (KD) in controlling seizure has been shown in many experimental and clinical studies, however, its mechanism of action still needs further clarification. The major goal of the present study was to investigate the influence of the commercially available KD and caloric restriction (CR) on the hippocampal afterdischarge (AD) threshold in rats, and concomitant biochemical changes, specifically concerning the kynurenine pathway, in plasma and the hippocampus. As expected, the rats on the KD showed higher AD threshold accompanied by increased plasma β-hydroxybutyrate level compared to the control group and the CR rats. This group presented also lowered tryptophan and elevated kynurenic acid levels in plasma with similar changes in the hippocampus. Moreover, the KD rats showed decreased levels of branched chain amino acids (BCAA) and aromatic amino acids (AAA) in plasma and the hippocampus. No regular biochemical changes were observed in the CR group. Our results are analogous to those detected after single administrations of fatty acids and valproic acid in our previous studies, specifically to an increase in the kynurenine pathway activity and changes in peripheral and central BCAA and AAA levels. This suggests that the anticonvulsant effect of the KD may be at least partially associated with those observed biochemical alternations.

Adenosine Kinase Isoforms in the Developing Rat Hippocampus after LiCl/Pilocarpine Status Epilepticus.

LiCl/pilocarpine status epilepticus (SE) induced in immature rats leads, after a latent period, to hippocampal hyperexcitability. The excitability may be influenced by adenosine, which exhibits anticonvulsant activity. The concentration of adenosine is regulated by adenosine kinase (ADK) present in two isoforms—ADK-L and ADK-S. The main goal of the study is to elucidate the changes in ADK isoform expression after LiCl/pilocarpine SE and whether potential changes, as well as inhibition of ADK by 5-iodotubercidin (5-ITU), may contribute to changes in hippocampal excitability during brain development. LiCl/pilocarpine SE was elicited in 12-day-old rats. Hippocampal excitability in immature rats was studied by the model of hippocampal afterdischarges (ADs), in which we demonstrated the potential inhibitory effect of 5-ITU. ADs demonstrated significantly decreased hippocampal excitability 3 days after SE induction, whereas significant hyperexcitability after 20 days compared to controls was shown. 5-ITU administration showed its inhibitory effect on the ADs in 32-day-old SE rats compared to SE rats without 5-ITU. Moreover, both ADK isoforms were examined in the immature rat hippocampus. The ADK-L isoform demonstrated significantly decreased expression in 12-day-old SE rats compared to the appropriate naïve rats, whereas increased ADK-S isoform expression was revealed. A decreasing ADK-L/-S ratio showed the declining dominance of ADK-L isoform during early brain development. LiCl/pilocarpine SE increased the excitability of the hippocampus 20 days after SE induction. The ADK inhibitor 5-ITU exhibited anticonvulsant activity at the same age. Age-related differences in hippocampal excitability after SE might correspond to the development of ADK isoform levels in the hippocampus.

Effect of ramosetron, a 5-HT3 receptor antagonist on the severity of seizures and memory impairment in electrical amygdala kindled rats

The entorhinal cortex (EC) plays a pivotal role in epileptogenesis and seizures. EC expresses high density of serotonergic receptors, especially 5-HT3 receptors. Cognitive impairment is common among people with epilepsy. The present study investigated the role of 5-HT3 receptor on the severity of seizures and learning and memory impairment by electrical kindling of amygdala in rats. The amygdala kindling was conducted in a chronic kindling manner in male Wistar rats. In fully kindled animals, ramosetron (as a potent and selective 5-HT3 receptor antagonist) was microinjected unilaterally (ad doses of 1, 10 or 100 µg/0.5 µl) into the EC 5 min before the novel object recognition (NOR) and Y-maze tests or kindling stimulations. Applying ramosetron at the concentration of 100 μg/0.5 µl (but not at 1 and 10 µg/0.5 µl) reduced afterdischarge (AD) duration and increased stage 4 latency in the kindled rats. Moreover, the obtained data from the NOR test showed that treatment by ramosetron (10 and 100 µg/0.5 µl) increased the discrimination index in the fully kindled animals. Microinjection of ramosetron (10 and 100 µg/0.5 µl) in fully kindled animals reversed the kindling induced changes in the percentage of spontaneous alternation in Y-maze task. The findings demonstrated an anticonvulsant role for a selective 5-HT3 receptor antagonist microinjected into the EC, therefore, suggesting an excitatory role for the EC 5-HT3 receptors in the amygdala kindling model of epilepsy. This anticonvulsive effect was accompanied with a restoring effect on cognitive behavior in NOR and Y-maze tests.

The antiepileptic activity of Safranal in kindling model of epilepsy in male rats

Recent studies suggested that safranal exerts anticonvulsant properties. The present study aimed to investigate the effect of safranal on epileptic activities in the amygdala electrical kindling model in male rats. Animals were implanted with a recording electrode on the skull and a tripolar in the amygdala. After 10 days of recovery, the afterdischarge (AD) threshold of each animal was determined and stimulated once daily the AD threshold for full kindling development. Then, parameters including afterdischarge duration (ADD), stage 4 latency (S4L), stage 5 duration (S5D), and stimulation threshold were determined before and after injection of safranal (0.05, 0.1, 0.2 ml/ kg; i.p). While the dose of 0.05 ml/kg had no significant effect, the dose of 0.1 ml/kg increased the AD threshold as well as S4L and decreased the S5D (P<0.05). Injection of 0.2 ml/kg of the safranal significantly decreased the ADD and S5D (P<0.05) and 83.3% of animals had no stage 4 and stage 5 of kindling (P<0.001). Based on the obtained data safranal has anticonvulsant effects dosedependently. It seems that a dose of 0.2 ml/kg is the minimum effective dose. Further investigation is warranted to conduct the clinical implications for the treatment of epileptic disorders.

Disparate properties of afterdischarges elicited by electric cortical stimulation in MRI lesional epilepsy patients with different surgical outcomes

PurposeThe purpose of this study was to demonstrate the prognostic value of afterdischarges(ADs) on surgical outcome by comparing the disparate properties in epilepsy patients with different surgical outcomes Methods27 lesional epilepsy patients were retrospectively analyzed. The brain region covered by subdural electrodes in each patient was dichotomized into the area of the brain lobe(s) where the MRI lesion is located (region ML) and other brain areas (region nML). The occurrence of ADs and ADs evolving into clinical seizure, ADs threshold and ADs duration in region ML and nML were compared between seizure-free (SF) and non-seizure-free (nSF) patients. ResultsA total of 2535 contacts were analyzed, and the total occurrence of ADs was 18.6% (471/2535). The overall occurrence of ADs in region ML (24.8%) was significantly higher than that in region nML (10.3%) (P < 0.001). In region ML, compared with SF patients, nSF patients had a lower occurrence of ADs (19.2% vs. 31.2%, P < 0.001), a higher occurrence of ADs evolves into clinical seizure (8.7% vs. 2.4%, P = 0.006), a higher ADs threshold (12.8 ± 4.1 mA vs. 11.0 ± 3.7 mA, P < 0.001) and a shorter ADs duration (15.3 ± 14.2 s vs. 20.6 ± 17.0 s, P < 0.001). However, in region nML, there was no significant difference in properties of ADs between SF and nSF patients. ConclusionHigher occurrence of ADs in region ML might predict a good outcome, whereas higher occurrence of ADs evolving into clinical seizure, higher ADs threshold and shorter ADs duration might predict an unfavorable surgical outcome. ADs might help predict surgical outcomes in epilepsy patients.

Modeling plasticity during epileptogenesis by long short term memory neural networks.

Understanding the pathogenesis of epilepsy including changes in synaptic pathways can improve our knowledge about epilepsy and development of new treatments. In this regard, data-driven models such as artificial neural networks, which are able to capture the effects of synaptic plasticity, can play an important role. This paper proposes long short term memory (LSTM) as the ideal architecture for modeling plasticity changes, and validates this proposal via experimental data. As a special class of recurrent neural networks (RNNs), LSTM is able to track information through time and control its flow via several gating mechanisms, which allow for maintaining the relevant and forgetting the irrelevant information. In our experiments, potentiation and depotentiation of motor circuit and perforant pathway as two forms of plasticity were respectively induced by kindled and kindled + transcranial magnetic stimulation of animal groups. In kindling, both procedure duration and gradual synaptic changes play critical roles. The stimulation of both groups continued for six days. Both after-discharge (AD) and seizure behavior as two biologically measurable effects of plasticity were recorded immediately post each stimulation. Three classes of artificial neural networks-LSTM, RNN, and feedforward neural network (FFNN)-were trained to predict AD and seizure behavior as indicators of plasticity during these six days. Results obtained from the collected data confirm the superiority of LSTM. For seizure behavior, the prediction accuracies achieved by these three models were 0.91 ± 0.01, 0.77 ± 0.02, and 0.59 ± 0.02%, respectively, and for AD, the prediction accuracies were 0.82 ± 0.01, 0.74 ± 0.08 and 0.42 ± 0.1, respectively.

Cortico-cortical evoked potential by single-pulse electrical stimulation is a generally safe procedure

ObjectiveCortico-cortical evoked potential (CCEP) by single-pulse electrical stimulation (SPES) is useful to investigate effective connectivity and cortical excitability. We aimed to clarify the safety of CCEPs. MethodsWe retrospectively analyzed 29 consecutive patients with intractable partial epilepsy undergoing chronic subdural grid implantation and CCEP recording. Repetitive SPES (1 Hz) was systematically applied to a pair of adjacent electrodes over almost all electrodes. We evaluated the incidences of afterdischarges (ADs) and clinical seizures. ResultsOut of 1283 electrode pairs, ADs and clinical seizures were observed in 12 and 5 pairs (0.94% and 0.39%, per electrode pair) in 7 and 3 patients (23.3% and 10.0%, per patient), respectively. Of the 18–82 pairs per patient, ADs and clinical seizures were induced in 0–4 and 0–3 pairs, respectively. Stimulating 4 SOZ (seizure onset zone) (2.5%) and 8 non-SOZ pairs (0.75%) resulted in ADs. We observed clinical seizures in stimulating 4 SOZ (2.5%) and 1 non-SOZ pair (0.09%). The incidence of clinical seizures varied significantly between SOZ and non-SOZ stimulations (p = 0.001), while the difference in AD incidence tended towards significance (p = 0.058). ConclusionAlthough caution should be taken in stimulating SOZ, CCEP is a safe procedure for presurgical evaluation. SignificanceCCEP is safe under the established protocol.

Analysis of risk factors and clinical sequelae of direct electrical cortical stimulation-induced seizures and afterdischarges in patients undergoing awake mapping.

Intraoperative stimulation has emerged as a crucial adjunct in neurosurgical oncology, aiding maximal tumor resection while preserving sensorimotor and language function. Despite increasing use in clinical practice of this stimulation, there are limited data on both intraoperative seizure (IS) frequency and the presence of afterdischarges (ADs) in patients undergoing such procedures. The objective of this study was to determine risk factors for IS or ADs, and to determine the clinical consequences of these intraoperative events. A retrospective chart review was performed for patients undergoing awake craniotomy (both first time and repeat) at a single institution from 2013 to 2018. Hypothesized risk factors for ADs/ISs in patients were evaluated for their effect on ADs and ISs, including tumor location, tumor grade (I-IV), genetic markers (isocitrate dehydrogenase 1/2, O 6-methylguanine-DNA methyltransferase [MGMT] promoter methylation, chromosome 1p/19q codeletion), tumor volume, preoperative seizure status (yes/no), and dosage of preoperative antiepileptic drugs for each patient. Clinical outcomes assessed in patients with IS or ADs were duration of surgery, length of stay, presence of perioperative deficits, and postoperative seizures. Chi-square analysis was performed for binary categorical variables, and a Student t-test was used to assess continuous variables. A total of 229 consecutive patients were included in the analysis. Thirty-five patients (15%) experienced ISs. Thirteen (37%) of these 35 patients had experienced seizures that were appreciated clinically and noted on electrocorticography simultaneously, while 8 patients (23%) experienced ISs that were electrographic alone (no obvious clinical change). MGMT promoter methylation was associated with an increased prevalence of ISs (OR 3.3, 95% CI 1.2-7.8, p = 0.02). Forty patients (18%) experienced ADs. Twenty-three percent of patients (9/40) with ISs had ADs prior to their seizure, although ISs and ADs were not statistically associated (p = 0.16). The presence of ADs appeared to be correlated with a shorter length of stay (5.1 ± 2.6 vs 6.1 ± 3.7 days, p = 0.037). Of the clinical features assessed, none were found to be predictive of ADs. Neither IS nor AD, or the presence of either IS or AD (65/229 patients), was a predictor for increased length of stay, presence of perioperative deficits, or postoperative seizures. ISs and ADs, while commonly observed during intraoperative stimulation for brain mapping, do not negatively affect patient outcomes.

The impact of surgery induced immune-nutritional change on the outgrowth of micrometastasis after potentially curative resection for gastric cancer.

e16581 Background: Whereas radical resection for gastric cancer is only life-saving option, resulting host response have been suggested to trigger the outgrowth of previously disseminated foci at distant anatomical sites via alteration of anti-tumor immunity. The prognostic nutrition index (PNI) which was calculated as 10 × serum Alb concentration (g/dL) + 0.005 × peripheral total lymphocyte count (/µL) is a surrogate marker of inflammation related nutritional decline and the imbalance of T lymphocyte differentiation. The aim of study was to evaluate the impact of perioperative change of PNI. Methods: The medical record of 567 gastric cancer patients who matched with the following inclusion criteria, R0 resection between 2006 and 2018, no preoperative anticancer treatment, pStage IB-IIIC according to UICC TNM classification and no other organ cancer at surgery, was identified from the prospectively maintained database. The postoperative laboratory data was routinely evaluated at POD 1, 3, 7 and first visit after discharge (AD). The PNI was compared through the perioperative course. Then the predictive value of low PNI-AD which defined as PNI &lt; 40 on the relapse free survival (RFS) after surgery was estimated by COX proportional hazards analysis. Results: The median value of PNI at base line, 1, 3, 7 POD and AD was 51.0, 35.9, 34.0, 38.3 and 48.2, respectively. The PNI as significantly decreased at 1, 3 and 7 POD. Though the PNI at AD had a proclivity to recover, which was still significantly lower than that at base line. During observation period after surgery, the recurrence was encountered in 80 patients. The 5-year RFS rate in patients of pStage IB (n = 164), II (n = 228) and III (n = 175) was 97.4%, 88.9% and 64.7%, respectively. The multivariate analysis identified female gender (HR: 1.715, 95%CI; 1.018-2.890, p = 0.04), pT3-4 (HR:3.620, 95%CI; 2.011-6.518, p &lt; 0.01), pN1-3 (HR:2.741, 95%CI; 1.428-5.263, p = 0.02), vessel invasion (+) (HR:2.666, 95%CI; 1.681-4.229, p &lt; 0.01), PNI-AD &lt; 40 (HR:1.833, 95%CI; 1.002-3.352, p = 0.04) were independent predictors of recurrence. The low PNI-AD was significantly related to the recurrence in the population of pStage III, but not in pStage IB and II. Conclusions: The retardation of postoperative recovery of PNI might evoke the distant metastasis.

Characteristics of visual evoked potentials related to the electro-clinical expression of reflex seizures in photosensitive patients with idiopathic occipital lobe epilepsy

Seizures provoked by visual stimuli may be induced by abnormal responses to light (photosensitivity) and structured patterns (patternsensitivity). In this study, we analysed visual evoked potentials (VEPs) in three different samples: i) 38 photosensitive patients (21 males, 17 females; mean age 10.0 ± 2.9 years) with idiopathic occipital lobe epilepsy and reflex seizures (RS); ii) 13 non-photosensitive patients (6 males, 7 females; mean age 11.7 ± 5.3) with idiopathic occipital lobe epilepsy; 20 healthy controls (12 males, 8 females; mean age 10.0 ± 3.4). After written informed consent, all subjects underwent a standard procedure of visual stimulation with intermittent light and pattern stimulation, under digital video-EEG recording. The EEG signal was processed off-line by averaging analysis for each stimulus to obtain the corresponding VEP. Comparisons among groups showed no significant differences for P100 latency. Higher P100 amplitude as well as higher after-discharge (AD) were found in photosensitive patients with RS. Thirty-seven of these patients had one or more RS during the procedure of stimulation for a total of 66 episodes. Significant increases of P100 amplitude and higher values of AD amplitude were found in relation to the occurrence of photoparoxysmal response (PPR) and/or seizures during full-field pattern stimulation. The increase in amplitude of the AD was higher when PPR was associated with seizures. The high amplitude of early VEP components confirms the abnormal hyperexcitability in the cortex of photosensitive patients with occipital lobe epilepsy. Moreover, the AD amplitude appears to be related to electro-clinical expression, being greater when PPR evolves into clinically evident seizures.