Epileptogenic network of focal epilepsies mapped with cortico-cortical evoked potentials

ObjectiveThe goal of this study was to investigate the spatial extent and functional organization of the epileptogenic network through cortico-cortical evoked potentials (CCEPs) in patients being evaluated with intracranial stereoelectroencephalography.MethodsWe retrospectively included 25 patients. We divided the recorded sites into three regions: epileptogenic zone (EZ); propagation zone (PZ); and noninvolved zone (NIZ). The root mean square of the amplitudes was calculated to reconstruct effective connectivity network. We also analyzed the N1/N2 amplitudes to explore the responsiveness influenced by epileptogenicity. Prognostic analysis was performed by comparing intra-region and inter-region connectivity between seizure-free and non-seizure-free groups.ResultsOur results confirmed that stimulation of the EZ caused the strongest responses on other sites within and outside the EZ. Moreover, we found a hierarchical connectivity pattern showing the highest connectivity strength within EZ, and decreasing connectivity gradient from EZ, PZ to NIZ. Prognostic analysis indicated a stronger intra-EZ connection in the seizure-free group.ConclusionThe EZ showed highest excitability and dominantly influenced other regions. Quantitative CCEPs can be useful in mapping epileptic networks and predicting surgical outcome.SignificanceThe generated computational connectivity model may enhance our understanding of epileptogenic networks and provide useful information for surgical planning and prognosis prediction.     

Effects of propofol on cortico-cortical evoked potentials in the dorsal language white matter pathway

ObjectiveIn order to evaluate the clinical utility even under general anesthesia, the present study aimed to clarify the effect of anesthesia on the cortico–cortical evoked potentials (CCEPs).MethodsWe analyzed 14 patients’ data in monitoring the integrity of the dorsal language pathway by using CCEPs both under general anesthesia with propofol and remifentanil and awake condition, with the main aim of clarifying the effect of anesthesia on the distribution and waveform of CCEPs.ResultsThe distribution of larger CCEP response sites, including the locus of the maximum CCEP response site, was marginally affected by anesthesia. With regard to similarity of waveforms, the mean waveform correlation coefficient indicated a strong agreement. CCEP N1 amplitude increased by an average of 25.8% from general anesthesia to waking, except three patients. CCEP N1 latencies had no correlation in changes between the two conditions.ConclusionsWe demonstrated that the distribution of larger CCEP responses was marginally affected by anesthesia and that the CCEP N1 amplitude had tendency to increase from general anesthesia to the awake condition.SignificanceThe CCEP method provides the efficiency of intraoperative monitoring for dorsal language white matter pathway even under general anesthesia.     

Vestibular evoked myogenic potentials and their clinical utility in patients with amyotrophic lateral sclerosis

ObjectiveTo evaluate the diagnostic value of vestibular evoked myogenic potentials (VEMPs) in the assessment of brainstem function integrity in patients with amyotrophic lateral sclerosis (ALS).MethodsThis was a prospective case-control study including 30 definite or probable ALS patients divided into two groups (with or without brainstem involvement) and 30 healthy controls. Cervical (c-), masseter (m-) and ocular VEMP (o-VEMP) measurements were obtained for all the participants.ResultsThe c-VEMP mean p13 and n23 were significantly prolonged in the ALS patients. The interside peak differences in p13 and n23 of c-VEMP and in n10 and p15 of o-VEMP were significantly prolonged. The rates of alteration in c-VEMP, m-VEMP and o-VEMP in the ALS patients were 67%, 40%, and 45%, respectively. The ALS patients with brainstem involvement had a significantly higher percentage of VEMP abnormalities than did those without brainstem involvement (p = 0.027).Conclusionsc-VEMP is a sensitive tool to detect lower levels of brainstem involvement. Impairments in o-VEMP and m-VEMP indicate involvement of the upper brainstem. The use of combined VEMPs may provide useful insights into the pathophysiological mechanism of ALS.SignificanceVEMPs may be useful in the evaluation of brainstem dysfunction in ALS patients.     

Recording cortico-cortical evoked potentials of the human arcuate fasciculus under general anaesthesia

ObjectiveWe examined the feasibility of using cortico-cortical evoked potentials (CCEPs) to monitor the major cortical white matter tract involved in language, the arcuate fasciculus (AF), during surgery under general anaesthesia.MethodsWe prospectively recruited nine patients undergoing surgery for lesions in the left peri-sylvian cortex, for whom awake surgery was not indicated. High angular resolution diffusion imaging (HARDI) tractography was used to localise frontal and temporal AF terminations, which guided intraoperative cortical strip placement.ResultsCCEPs were successfully evoked in 5/9 patients, showing a positive potential (P1) at 12 ms and a negative component (N1) at 21 ms when stimulating from the frontal lobe and recording in the temporal lobe. CCEP responses peaked in the posterior middle temporal gyrus. No CCEPs were evoked when stimulating temporal sites and recording from frontal contacts.ConclusionFor the first time, we show that CCEPs can be evoked from the peri-sylvian cortices also in adult patients who are not candidates for awake procedures. Our results are akin to those described in the awake setting and suggest the recorded activity is conveyed by the arcuate fasciculus.SignificanceThis intraoperative approach may have promising implications in reducing deficits in patients that require surgery in language areas under general anesthesia.     

A systematic exploration of parameters affecting evoked intracranial potentials in patients with epilepsy

BackgroundBrain activity is constrained by and evolves over a network of structural and functional connections. Corticocortical evoked potentials (CCEPs) have been used to measure this connectivity and to discern brain areas involved in both brain function and disease. However, how varying stimulation parameters influences the measured CCEP across brain areas has not been well characterized.ObjectiveTo better understand the factors that influence the amplitude of the CCEPs as well as evoked gamma-band power (70–150 Hz) resulting from single-pulse stimulation via cortical surface and depth electrodes.MethodsCCEPs from 4370 stimulation-response channel pairs were recorded across a range of stimulation parameters and brain regions in 11 patients undergoing long-term monitoring for epilepsy. A generalized mixed-effects model was used to model cortical response amplitudes from 5 to 100 ms post-stimulation.ResultsStimulation levels <5.5 mA generated variable CCEPs with low amplitude and reduced spatial spread. Stimulation at ≥5.5 mA yielded a reliable and maximal CCEP across stimulation-response pairs over all regions. These findings were similar when examining the evoked gamma-band power. The amplitude of both measures was inversely correlated with distance. CCEPs and evoked gamma power were largest when measured in the hippocampus compared with other areas. Larger CCEP size and evoked gamma power were measured within the seizure onset zone compared with outside this zone.ConclusionThese results will help guide future stimulation protocols directed at quantifying network connectivity across cognitive and disease states.     

Delayed neonatal visual evoked potentials are associated to asymmetric growth pattern in twins

ObjectivesTo study the association between intrauterine growth and visual pathways maturation by neonatal visual evoked potentials (VEPs) in twins, in view of a possible prognostic role.MethodsSeventy-four twin neonates from 37 pregnancies were selected based on gestational age of more than 30 weeks and uneventful perinatal clinical course. Flash VEPs were recorded at the same postmenstrual age in each twin pair. The association between P2 latency and anthropometric variables at birth was analyzed by comparison within each twin pair and regarding each variable as ordered difference between the two twins.ResultsAnalysis of differences within each twin pair highlighted that inter-twin difference in P2 latency was significantly related to difference in ponderal index (PI) (p = 0.048).Expressing the difference in latency as a categorical binary variable, the correlation was significant for both difference in PI, (median difference = −0.36, 95% CI −0.54 to −0.14, p = 0.001) and difference in body mass index (BMI), (median difference = −1.06, 95% CI −1.74 to −0.29, p = 0.006).ConclusionsLower values of PI and BMI differences are associated to delayed VEP latency in twin pairs.SignificanceVEP latency suggests reduced myelination of visual pathways when difference in growth pattern occurs in twins.     

Effects of stimulation intensity on intracranial cortico-cortical evoked potentials: A titration study

ObjectiveThe aim of the present study was to investigate the optimal stimulation parameters for eliciting cortico-cortical evoked potentials (CCEPs) for mapping functional and epileptogenic networks.MethodsWe studied 13 patients with refractory epilepsy undergoing intracranial EEG monitoring. We systematically titrated the intensity of single-pulse electrical stimulation at multiple sites to assess the effect of increasing current on salient features of CCEPs such as N1 potential magnitude, signal to noise ratio, waveform similarity, and spatial distribution of responses. Responses at each incremental stimulation setting were compared to each other and to a final set of responses at the maximum intensity used in each patient (3.5–10 mA, median 6 mA).ResultsWe found that with a biphasic 0.15 ms/phase pulse at least 2–4 mA is needed to differentiate between non-responsive and responsive sites, and that stimulation currents of 6–7 mA are needed to maximize amplitude and spatial distribution of N1 responses and stabilize waveform morphology.ConclusionsWe determined a minimum stimulation threshold necessary for eliciting CCEPs, as well as a point at which the current-dependent relationship of several response metrics all saturate.SignificanceThis titration study provides practical, immediate guidance on optimal stimulation parameters to study specific features of CCEPs, which have been increasingly used to map both functional and epileptic brain networks in humans.     

Contribution of different somatosensory afferent input to subcortical somatosensory evoked potentials in humans

ObjectivesTo investigate the subcortical somatosensory evoked potentials (SEPs) to electrical stimulation of either muscle or cutaneous afferents.MethodsSEPs were recorded in 6 patients suffering from Parkinson’s disease (PD) who underwent electrode implantation in the pedunculopontine (PPTg) nucleus area. We compared SEPs recorded from the scalp and from the intracranial electrode contacts to electrical stimuli applied to: 1) median nerve at the wrist, 2) abductor pollicis brevis motor point, and 3) distal phalanx of the thumb. Also the high-frequency oscillations (HFOs) were analysed.ResultsAfter median nerve and pure cutaneous (distant phalanx of the thumb) stimulation, a P1-N1 complex was recorded by the intracranial lead, while the scalp electrodes recorded the short-latency far-field responses (P14 and N18). On the contrary, motor point stimulation did not evoke any low-frequency component in the PPTg traces, nor the N18 potential on the scalp. HFOs were recorded to stimulation of all modalities by the PPTg electrode contacts.ConclusionsStimulus processing within the cuneate nucleus depends on modality, since only the cutaneous input activates the complex intranuclear network possibly generating the scalp N18 potential.SignificanceOur results shed light on the subcortical processing of the somatosensory input of different modalities.     

A prewarning sign for hearing loss by brainstem auditory evoked potentials during microvascular decompression surgery for hemifacial spasm

ObjectiveWe aimed to define the prewarning sign of brainstem auditory evoked potentials (BAEPs) associated with cerebellar retraction (CR) during microvascular decompression surgery for hemifacial spasm.MethodsA total of 241 patients with a latency prolongation of 1 ms or an amplitude decrement of 50% of wave V were analyzed. According to BAEPs before significant changes during CR, patients were classified into Groups A (latency prolongation of wave I [≥0.5 ms] without prolongation of the I–III interpeak interval [<0.5 ms]) and B (no latency prolongation of wave I [<0.5 ms] with prolongation of the I–III interpeak interval [≥0.5 ms]). BAEPs and postoperative hearing loss (HL) were compared between the two groups.ResultsGroup B comprised 160 (66.4%) patients. With maximal changes in wave V, latency prolongation (≥1 ms) with amplitude decrement (≥50%) was more common in Group B (p < 0.018). At the end of the operation, wave V loss was observed in 11 patients, including 10 patients from Group B. Five patients developed postoperative HL; all were from Group B.ConclusionsLatency prolongation of wave III during CR was associated with serious BAEPs changes and postoperative HL.SignificanceLatency prolongation of wave III is a significant prewarning sign.     

Differentiating neurodegenerative parkinsonian syndromes using vestibular evoked myogenic potentials and balance assessment

ObjectiveVestibular evoked myogenic potentials (VEMP) were investigated to differentiate between parkinsonian syndromes. We correlated balance and VEMP parameters to investigate the VEMP brainstem circuits as possible origin for postural instability.MethodsWe assessed clinical status, ocular and cervical VEMP (oVEMP, cVEMP) and conducted a balance assessment (posturography, Activities-specific Balance Confidence Scale, Berg Balance Scale, modified Barthel Index) in 76 subjects: 30 with Parkinson’s disease (PD), 16 with atypical parkinsonism (AP) and 30 healthy controls. VEMP were elicited by using a mini-shaker on the forehead.ResultsPatients with PD had a prolonged oVEMP n10 in comparison to controls and prolonged p15 compared to controls and AP. Patients with AP showed reduced oVEMP amplitudes compared to PD and controls. CVEMP did not differ between groups. Postural impairment was higher in AP compared to controls and PD, particularly in the rating scales. No correlations between VEMP and posturography were found. A support vector machine classifier was able to automatically classify controls and patient subgroups with moderate to good accuracy based on oVEMP latencies and balance questionnaires.ConclusionsBoth oVEMP and posturography, but not cVEMP, may be differentially affected in PD and AP. We did not find evidence that impairment of the cVEMP or oVEMP pathways is directly related to postural impairment.SignificanceOVEMP and balance assessment could be implemented in the differential diagnostic work-up of parkinsonian syndromes.     

Early nociceptive evoked potentials (NEPs) recorded from the scalp

ObjectiveNeurophysiological investigation of nociceptive pathway has so far been limited to late cortical responses. We sought to detect early components of the cortical evoked potentials possibly reflecting primary sensory activity.MethodsThe 150 IDE micropatterned electrode was used to selectively activate Aδ intraepidermic fibres of the right hand dorsum in 25 healthy subjects and 3 patients suffering from trigeminal neuralgia. Neurographic recordings were performed to assess type of stimulated fibres and check selectivity. Cortical evoked potentials were recorded from C3′-Fz and Cz-Au1.ResultsNeurographic recordings confirmed selective activation of Aδ fibres. Early components were detected after repetitive stimulation (0.83/s rate and 250–500 averages); the first negative component occured at 40 ms (N40) on the contralateral scalp.ConclusionsThe provided data support the hypothesis that N40 could be the cortical primary response conducted by fast Aδ fibres.SignificanceThis is the first report of early, possibly primary, cortical responses in humans by nociceptive peripheral stimulation. Although not perfected yet to allow widespread diagnostic use, this is probably the only method to allow fully objective evaluation of the nociceptive system, with important future implications in experimental and clinical neurophysiology.     

Fixation-related potentials in naming speed: A combined EEG and eye-tracking study on children with dyslexia

ObjectiveWe combined electroencephalography (EEG) and eye-tracking recordings to examine the underlying factors elicited during the serial Rapid-Automatized Naming (RAN) task that may differentiate between children with dyslexia (DYS) and chronological age controls (CAC).MethodsThirty children with DYS and 30 CAC (M_age = 9.79 years; age range 7.6 through 12.1 years) performed a set of serial RAN tasks. We extracted fixation-related potentials (FRPs) under phonologically similar (rime-confound) or visually similar (resembling lowercase letters) and dissimilar (non-confounding and discrete uppercase letters, respectively) control tasks.ResultsResults revealed significant differences in FRP amplitudes between DYS and CAC groups under the phonologically similar and phonologically non-confounding conditions. No differences were observed in the case of the visual conditions. Moreover, regression analysis showed that the average amplitude of the extracted components significantly predicted RAN performance.ConclusionFRPs capture neural components during the serial RAN task informative of differences between DYS and CAC and establish a relationship between neurocognitive processes during serial RAN and dyslexia.SignificanceWe suggest our approach as a methodological model for the concurrent analysis of neurophysiological and eye-gaze data to decipher the role of RAN in reading.     

Electro-clinical features in epileptic children with chromosome 15q duplication syndrome

ObjectiveWe aimed to describe epilepsy and EEG patterns related to vigilance states and age, in chromosome15-long-arm-duplication-syndrome (dup15q) children with epilepsy, in both duplication types: interstitial (intdup15) and isodicentric (idic15).MethodsClinical data and 70 EEGs of 12 patients (5 intdup15, 7 idic15), followed from 4.5 m.o to 17y4m (median follow-up 8y3m), were retrospectively reviewed. EEGs were analyzed visually and using power spectrum analysis.ResultsSeventy video-EEGs were analyzed (1–16 per patient, median 6), follow-up lasting up to 8y10m (median 4y2m): 25 EEGs in intdup15 (8 m.o to 12y.o, median 4y6m) and 45 EEGs in idic15 (7 m.o to 12 y.o, median 15 m). Epilepsy: 6 West syndrome (WS) (2intdup15, 4idic15); 4 Lennox-Gastaut syndromes (LGS) (1 intdup15, 3 idic15), 2 evolving from WS; focal epilepsy (3 intdup15). In idic15, WS displayed additional myoclonic seizures (3), atypical (4) or no hypsarrhythmia (2) and posterior predominant spike and polyspike bursts (4). Beta-band rapid-rhythms (RR): present in 11 patients, power decreased during non-REM-sleep, localization shifted from diffuse to anterior, peak frequency increased with age.ConclusionWS with peculiar electro-clinical features and LGS, along with beta-band RR decreasing in non-REM-sleep and shifting from diffuse to anterior localization with age are recognizable features pointing towards dup15q diagnosis in children with autism spectrum disorder and developmental delay.SignificanceThis study describes electroclinical features in both interstitial and isodicentric duplications of chromosome 15q, in epileptic children, including some recent extensions regarding sleep features; and illustrates how the temporo-spatial organization of beta oscillations can be of significant help in directing towards dup15q diagnosis hypothesis.     

Intracortical GABAergic dysfunction in patients with fatigue and dysexecutive syndrome after COVID-19

ObjectiveA high proportion of patients experience fatigue and impairment of cognitive functions after coronavirus disease 2019 (COVID-19). Here we applied transcranial magnetic stimulation (TMS) to explore the activity of the main inhibitory intracortical circuits within the primary motor cortex (M1) in a sample of patients complaining of fatigue and presenting executive dysfunction after resolution of COVID-19 with neurological manifestations.MethodsTwelve patients who recovered from typical COVID-19 pneumonia with neurological complications and complained of profound physical and mental fatigue underwent, 9 to 13 weeks from disease onset, a psychometric evaluation including a self-reported fatigue numeric-rating scale (FRS, Fatigue Rating Scale) and the Frontal Assessment Battery (FAB). Intracortical activity was evaluated by means of well-established TMS protocols including short-interval intracortical inhibition (SICI), reflecting GABA_A-mediated inhibition, long-interval intracortical inhibition (LICI), a marker of GABA_B receptor activity, and short-latency afferent inhibition (SAI) that indexes central cholinergic transmission. TMS data were compared to those obtained in a control group of ten healthy subjects (HS) matched by age, sex and education level.ResultsPost-COVID-19 patients reported marked fatigue according to FRS score (8.1 ± 1.7) and presented pathological scores at the FAB based on Italian normative data (12.2 ± 0.7). TMS revealed marked reduction of SICI, and disruption of LICI as compared to HS. SAI was also slightly diminished.ConclusionsThe present study documents for the first time reduced GABAergic inhibition in the M1 in patients who recovered from COVID-19 with neurological complications and manifested fatigue and dysexecutive syndrome.SignificanceTMS may serve as diagnostic tool in cognitive disturbances and fatigue in post-COVID-19 patients.     

Clinical and advanced neurophysiology in the prognostic and diagnostic evaluation of disorders of consciousness: review of an IFCN-endorsed expert group

The analysis of spontaneous EEG activity and evoked potentials is a cornerstone of the instrumental evaluation of patients with disorders of consciousness (DoC). The past few years have witnessed an unprecedented surge in EEG-related research applied to the prediction and detection of recovery of consciousness after severe brain injury, opening up the prospect that new concepts and tools may be available at the bedside. This paper provides a comprehensive, critical overview of both consolidated and investigational electrophysiological techniques for the prognostic and diagnostic assessment of DoC. We describe conventional clinical EEG approaches, then focus on evoked and event-related potentials, and finally we analyze the potential of novel research findings. In doing so, we (i) draw a distinction between acute, prolonged and chronic phases of DoC, (ii) attempt to relate both clinical and research findings to the underlying neuronal processes and (iii) discuss technical and conceptual caveats. The primary aim of this narrative review is to bridge the gap between standard and emerging electrophysiological measures for the detection and prediction of recovery of consciousness. The ultimate scope is to provide a reference and common ground for academic researchers active in the field of neurophysiology and clinicians engaged in intensive care unit and rehabilitation.     

The value of sensory nerve conduction studies in the diagnosis of Guillain–Barré syndrome

Electrophysiology plays a determinant role in Guillain–Barré syndrome (GBS) diagnosis, classification, and prognostication. However, traditional electrodiagnostic (EDX) criteria for GBS rely on motor nerve conduction studies (NCS) and are suboptimal early in the course of the disease or in the setting of GBS variants. Sensory nerve conduction studies, including the sural-sparing pattern and the sensory ratio are not yet included in EDX criteria despite their well-established role in GBS diagnosis. The aim of this review is to discuss the diagnostic value of sensory NCS in GBS, their role in establishing the diagnosis and predicting the outcome according to the various subtypes of the disease.     

Enlarged high frequency oscillations of the median nerve somatosensory evoked potential and survival in amyotrophic lateral sclerosis

ObjectiveA large N20 and P25 of the median nerve somatosensory evoked potential (SEP) predicts short survival in amyotrophic lateral sclerosis (ALS). We investigated whether high frequency oscillations (HFOs) over N20 are enlarged and associated with survival in ALS.MethodsA total of 145 patients with ALS and 57 healthy subjects were studied. We recorded the median nerve SEP and measured the onset-to-peak amplitude of N20 (N20o-p), and peak-to-peak amplitude between N20 and P25 (N20p-P25p). We obtained early and late HFO potentials by filtering SEP between 500 and 1 kHz, and measured the peak-to-peak amplitude. We followed up patients until endpoints (death or tracheostomy) and analyzed the relationship between SEP or HFO amplitudes and survival using a Cox analysis.ResultsPatients showed larger N20o-p, N20p-P25p, and early and late HFO amplitudes than the control values. N20p-P25p was associated with survival periods (p = 0.0004), while early and late HFO amplitudes showed no significant association with survival (p = 0.4307, and p = 0.6858, respectively).ConclusionsThe HFO amplitude in ALS is increased, but does not predict survival.SignificanceThe enlarged HFOs in ALS might be a compensatory phenomenon to the hyperexcitability of the sensory cortex pyramidal neurons.     

Difference in background factors between responders to gabapentin enacarbil treatment and responders to placebo: pooled analyses of two randomized,double-blind,placebo-controlled studies in Japanese patients with restless legs syndrome

ObjectiveRestless legs syndrome (RLS) is a sensorimotor disorder that is characterized by uncomfortable and unpleasant sensations mainly in the legs. Two placebo-controlled studies (Phase II/III and post-marketing) in Japanese patients with RLS failed to demonstrate the efficacy of gabapentin enacarbil (GE) 600 mg in the change from baseline in International Restless Legs Syndrome Rating Scale (IRLS) score at the end of the treatment period. The high response to placebo is thought to be a possible reason why the post-marketing study failed. The objectives of these post hoc analyses were to determine potential predictive factors associated with improvement in IRLS score with GE treatment and to identify subgroups with higher placebo responses.MethodsWe combined data from the two Japanese studies and analyzed change from baseline in IRLS score in the pooled population and subgroups defined by several patient characteristics. Moreover, we calculated the variable importance of each factor and performed predictive enrichment analysis to identify an enrichable subpopulation with greater improvement by GE treatment.ResultsThe post hoc analyses suggested that higher baseline IRLS score (≥21) and higher body mass index (≥25 kg/m²) were associated with higher placebo responses. On the other hand, positive family history of RLS, prior use of dopaminergic receptor agonists, and higher baseline ferritin level (≥50 ng/mL) were associated with higher responses to GE.ConclusionsOur results suggest that patients with typical idiopathic RLS characteristics, including positive family history and no low ferritin level, would be expected to derive the greatest benefits from GE treatment.     

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.