Neuronal Firing and Waveform Alterations through Ictal Recruitment in Humans.

Analyzing neuronal activity during human seizures is pivotal to understanding mechanisms of seizure onset and propagation. These analyses, however, invariably using extracellular recordings, are greatly hindered by various phenomena that are well established in animal studies: changes in local ionic concentration, changes in ionic conductance, and intense, hypersynchronous firing. The first two alter the action potential waveform, whereas the third increases the "noise"; all three factors confound attempts to detect and classify single neurons. To address these analytical difficulties, we developed a novel template-matching-based spike sorting method, which enabled identification of 1239 single neurons in 27 patients (13 female) with intractable focal epilepsy, that were tracked throughout multiple seizures. These new analyses showed continued neuronal firing with widespread intense activation and stereotyped action potential alterations in tissue that was invaded by the seizure: neurons displayed increased waveform duration (p < 0.001) and reduced amplitude (p < 0.001), consistent with prior animal studies. By contrast, neurons in "penumbral" regions (those receiving intense local synaptic drive from the seizure but without neuronal evidence of local seizure invasion) showed stable waveforms. All neurons returned to their preictal waveforms after seizure termination. We conclude that the distinction between "core" territories invaded by the seizure versus "penumbral" territories is evident at the level of single neurons. Furthermore, the increased waveform duration and decreased waveform amplitude are neuron-intrinsic hallmarks of seizure invasion that impede traditional spike sorting and could be used as defining characteristics of local recruitment.SIGNIFICANCE STATEMENT Animal studies consistently show marked changes in action potential waveform during epileptic discharges, but acquiring similar evidence in humans has proven difficult. Assessing neuronal involvement in ictal events is pivotal to understanding seizure dynamics and in defining clinical localization of epileptic pathology. Using a novel method to track neuronal firing, we analyzed microelectrode array recordings of spontaneously occurring human seizures, and here report two dichotomous activity patterns. In cortex that is recruited to the seizure, neuronal firing rates increase and waveforms become longer in duration and shorter in amplitude as the neurons are recruited to the seizure, while penumbral tissue shows stable action potentials, in keeping with the "dual territory" model of seizure dynamics.

Cross-scale effects of neural interactions during human neocortical seizure activity.

Small-scale neuronal networks may impose widespread effects on large network dynamics. To unravel this relationship, we analyzed eight multiscale recordings of spontaneous seizures from four patients with epilepsy. During seizures, multiunit spike activity organizes into a submillimeter-sized wavefront, and this activity correlates significantly with low-frequency rhythms from electrocorticographic recordings across a 10-cm-sized neocortical network. Notably, this correlation effect is specific to the ictal wavefront and is absent interictally or from action potential activity outside the wavefront territory. To examine the multiscale interactions, we created a model using a multiscale, nonlinear system and found evidence for a dual role for feedforward inhibition in seizures: while inhibition at the wavefront fails, allowing seizure propagation, feedforward inhibition of the surrounding centimeter-scale networks is activated via long-range excitatory connections. Bifurcation analysis revealed that distinct dynamical pathways for seizure termination depend on the surrounding inhibition strength. Using our model, we found that the mesoscopic, local wavefront acts as the forcing term of the ictal process, while the macroscopic, centimeter-sized network modulates the oscillatory seizure activity.

Role of paroxysmal depolarization in focal seizure activity.

We analyze the role of inhibition in sustaining focal epileptic seizure activity. We review ongoing seizure activity at the mesoscopic scale that can be observed with microelectrode arrays as well as at the macroscale of standard clinical EEG. We provide clinical, experimental, and modeling data to support the hypothesis that paroxysmal depolarization (PD) is a critical component of the ictal machinery. We present dual-patch recordings in cortical cultures showing reduced synaptic transmission associated with presynaptic occurrence of PD, and we find that the PD threshold is cell size related. We further find evidence that optically evoked PD activity in parvalbumin neurons can promote propagation of neuronal excitation in neocortical networks in vitro. Spike sorting results from microelectrode array measurements around ictal wave propagation in human focal seizures demonstrate a strong increase in putative inhibitory firing with an approaching excitatory wave, followed by a sudden reduction of firing at passage. At the macroscopic level, we summarize evidence that this excitatory ictal wave activity is strongly correlated with oscillatory activity across a centimeter-sized cortical network. We summarize Wilson-Cowan-type modeling showing how inhibitory function is crucial for this behavior. Our findings motivated us to develop a network motif of neurons in silico, governed by a reduced version of the Hodgkin-Huxley formalism, to show how feedforward, feedback, PD, and local failure of inhibition contribute to observed dynamics across network scales. The presented multidisciplinary evidence suggests that the PD not only is a cellular marker or epiphenomenon but actively contributes to seizure activity.NEW & NOTEWORTHY We present mechanisms of ongoing focal seizures across meso- and macroscales of microelectrode array and standard clinical recordings, respectively. We find modeling, experimental, and clinical evidence for a dual role of inhibition across these scales: local failure of inhibition allows propagation of a mesoscopic ictal wave, whereas inhibition elsewhere remains intact and sustains macroscopic oscillatory activity. We present evidence for paroxysmal depolarization as a mechanism behind this dual role of inhibition in shaping ictal activity.

Multiscale recordings reveal the dynamic spatial structure of human seizures.

The cellular activity underlying human focal seizures, and its relationship to key signatures in the EEG recordings used for therapeutic purposes, has not been well characterized despite many years of investigation both in laboratory and clinical settings. The increasing use of microelectrodes in epilepsy surgery patients has made it possible to apply principles derived from laboratory research to the problem of mapping the spatiotemporal structure of human focal seizures, and characterizing the corresponding EEG signatures. In this review, we describe results from human microelectrode studies, discuss some data interpretation pitfalls, and explain the current understanding of the key mechanisms of ictogenesis and seizure spread.

Single unit action potentials in humans and the effect of seizure activity.

Spike-sorting algorithms have been used to identify the firing patterns of isolated neurons ('single units') from implanted electrode recordings in patients undergoing assessment for epilepsy surgery, but we do not know their potential for providing helpful clinical information. It is important therefore to characterize both the stability of these recordings and also their context. A critical consideration is where the units are located with respect to the focus of the pathology. Recent analyses of neuronal spiking activity, recorded over extended spatial areas using microelectrode arrays, have demonstrated the importance of considering seizure activity in terms of two distinct spatial territories: the ictal core and penumbral territories. The pathological information in these two areas, however, is likely to be very different. We investigated, therefore, whether units could be followed reliably over prolonged periods of times in these two areas, including during seizure epochs. We isolated unit recordings from several hundred neurons from four patients undergoing video-telemetry monitoring for surgical evaluation of focal neocortical epilepsies. Unit stability could last in excess of 40 h, and across multiple seizures. A key finding was that in the penumbra, spike stereotypy was maintained even during the seizure. There was a net tendency towards increased penumbral firing during the seizure, although only a minority of units (10-20%) showed significant changes over the baseline period, and notably, these also included neurons showing significant reductions in firing. In contrast, within the ictal core territories, regions characterized by intense hypersynchronous multi-unit firing, our spike sorting algorithms failed as the units were incorporated into the seizure activity. No spike sorting was possible from that moment until the end of the seizure, but recovery of the spike shape was rapid following seizure termination: some units reappeared within tens of seconds of the end of the seizure, and over 80% reappeared within 3 min (τrecov = 104 ± 22 s). The recovery of the mean firing rate was close to pre-ictal levels also within this time frame, suggesting that the more protracted post-ictal state cannot be explained by persistent cellular neurophysiological dysfunction in either the penumbral or the core territories. These studies lay the foundation for future investigations of how these recordings may inform clinical practice.See Kimchi and Cash (doi:10.1093/awv264) for a scientific commentary on this article.

Ictal high frequency oscillations distinguish two types of seizure territories in humans.

High frequency oscillations have been proposed as a clinically useful biomarker of seizure generating sites. We used a unique set of human microelectrode array recordings (four patients, 10 seizures), in which propagating seizure wavefronts could be readily identified, to investigate the basis of ictal high frequency activity at the cortical (subdural) surface. Sustained, repetitive transient increases in high gamma (80-150 Hz) amplitude, phase-locked to the low-frequency (1-25 Hz) ictal rhythm, correlated with strong multi-unit firing bursts synchronized across the core territory of the seizure. These repetitive high frequency oscillations were seen in recordings from subdural electrodes adjacent to the microelectrode array several seconds after seizure onset, following ictal wavefront passage. Conversely, microelectrode recordings demonstrating only low-level, heterogeneous neural firing correlated with a lack of high frequency oscillations in adjacent subdural recording sites, despite the presence of a strong low-frequency signature. Previously, we reported that this pattern indicates a failure of the seizure to invade the area, because of a feedforward inhibitory veto mechanism. Because multi-unit firing rate and high gamma amplitude are closely related, high frequency oscillations can be used as a surrogate marker to distinguish the core seizure territory from the surrounding penumbra. We developed an efficient measure to detect delayed-onset, sustained ictal high frequency oscillations based on cross-frequency coupling between high gamma amplitude and the low-frequency (1-25 Hz) ictal rhythm. When applied to the broader subdural recording, this measure consistently predicted the timing or failure of ictal invasion, and revealed a surprisingly small and slowly spreading seizure core surrounded by a far larger penumbral territory. Our findings thus establish an underlying neural mechanism for delayed-onset, sustained ictal high frequency oscillations, and provide a practical, efficient method for using them to identify the small ictal core regions. Our observations suggest that it may be possible to reduce substantially the extent of cortical resections in epilepsy surgery procedures without compromising seizure control.

Tuning of the human neocortex to the temporal dynamics of attended events.

Previous studies raise the hypothesis that attentional bias in the phase of neocortical excitability fluctuations (oscillations) represents a fundamental mechanism for tuning the brain to the temporal dynamics of task-relevant event patterns. To evaluate this hypothesis, we recorded intracranial electrocortical activity in human epilepsy patients while they performed an audiovisual stream selection task. Consistent with our hypothesis, (1) attentional modulation of oscillatory entrainment operates in a distinct network of areas including auditory, visual, posterior parietal, inferior motor, inferior frontal and superior midline frontal cortex, (2) the degree of oscillatory entrainment depends on the predictability of the stimulus stream, and (3) the attentional phase shift of entrained oscillation cooccurs with classical attentional effects observed on phase-locked evoked activity in sensory-specific areas but seems to operate on entrained low-frequency oscillations that cannot be explained by sensory activity evoked at the rate of stimulation. Thus, attentional entrainment appears to tune a network of brain areas to the temporal dynamics of behaviorally relevant event streams, contributing to its perceptual and behavioral selection.

Human interictal epileptiform discharges are bidirectional traveling waves echoing ictal discharges.

Interictal epileptiform discharges (IEDs), also known as interictal spikes, are large intermittent electrophysiological events observed between seizures in patients with epilepsy. Although they occur far more often than seizures, IEDs are less studied, and their relationship to seizures remains unclear. To better understand this relationship, we examined multi-day recordings of microelectrode arrays implanted in human epilepsy patients, allowing us to precisely observe the spatiotemporal propagation of IEDs, spontaneous seizures, and how they relate. These recordings showed that the majority of IEDs are traveling waves, traversing the same path as ictal discharges during seizures, and with a fixed direction relative to seizure propagation. Moreover, the majority of IEDs, like ictal discharges, were bidirectional, with one predominant and a second, less frequent antipodal direction. These results reveal a fundamental spatiotemporal similarity between IEDs and ictal discharges. These results also imply that most IEDs arise in brain tissue outside the site of seizure onset and propagate toward it, indicating that the propagation of IEDs provides useful information for localizing the seizure focus.

Intracortical electroencephalography in acute brain injury.

OBJECTIVE: Continuous electroencephalography (EEG) is used in patients with neurological injury to detect electrographic seizures and clinically important changes in brain function. Scalp EEG has poor spatial resolution, is often contaminated by artifact, and frequently demonstrates activity that is suspicious for but not diagnostic of ictal activity. We hypothesized that bedside placement of an intracortical multicontact electrode would allow for improved monitoring of cortical potentials in critically ill neurological patients. METHODS: Sixteen individuals with brain injury, requiring invasive neuromonitoring, underwent implantation of an eight-contact minidepth electrode. RESULTS: Intracortical EEG (ICE) was successfully performed and compared with scalp EEG in 14 of these 16 individuals. ICE provided considerable improvement in signal-to-noise ratio compared with surface EEG, demonstrating clinically important findings in 12 of 14 patients (86%) including electrographic seizures (n = 10) and acute changes related to secondary neurological injury (n = 2, 1 ischemia, 1 hemorrhage). In patients with electrographic seizures detected by ICE, scalp EEG demonstrated no concurrent ictal activity in six, nonictal-appearing rhythmic delta in two, and intermittently correlated ictal activity in two. In two patients with secondary neurological complications, ICE demonstrated prominent attenuation 2 to 6 hours before changes in other neuromonitoring modalities and more than 8 hours before the onset of clinical deterioration. INTERPRETATION: ICE can provide high-fidelity intracranial EEG in an intensive care unit setting, can detect ictal discharges not readily apparent on scalp EEG, and can identify early changes in brain activity caused by secondary neurological complications. We predict that ICE will facilitate the development of EEG-based alarm systems and lead to prevention of secondary neuronal injury.

Hemodynamically significant cardiac arrhythmias during general anesthesia for spine surgery: A case series and literature review.

BACKGROUND CONTEXT: Hemodynamically significant bradycardia and cardiac arrest (CA) are rare under general anesthesia (GA) for spine surgery. Although patient risks are well defined, emerging data implicate surgical, anesthetic and neurologic factors which should be considered in the immediate management and decision to continue or terminate surgery. PURPOSE: To characterize causes and contributors to significant arrhythmias during spine surgery. We also provide an updated literature review to inform spine care teams and aid in the management of intraoperative bradycardia and CA. STUDY DESIGN: Case series and literature review. PATIENT SAMPLE: Six patients who underwent spine surgery from 03/2016 to 01/2020 at a single institution and developed unexpected hemodynamically significant arrhythmia. OUTCOME MEASURES: Our primary outcome was to identify potential risk factors of interest for significant arrhythmia during spine surgery. METHODS: Medical records of patients who underwent spine surgery from 03/2016 to 01/2020 at a single institution and developed unexpected hemodynamically significant arrhythmia during spine surgery were identified from a departmental Quality Assurance Database. We evaluated the presence/absence of patient, surgical, anesthetic and neurologic risk factors and estimated the most likely etiology of the event, immediate and subsequent management, whether surgery was postponed or continued and outcomes. RESULTS: We found a temporal relationship of bradyarrhythmia and CA after somatosensory evoked potential (SSEP) stimulation in 4/6 cases and pharmacy/polypharmacy in 2/6. Surgery was completed in 4/6 patients, and terminated in 2/6 (subsequently completed in both). We found no adverse outcomes in any patients. Our literature review predominately identified case reports for guidance to support decision making. New literaure suggests peripheral nerve blocks and opioid-sparing anesthetic agents should also be considered. CONCLUSIONS: Significant bradycardia and CA during spine surgery does not always require termination of the surgical procedure. Decision making should be undertaken in each case individually, with an updated awareness of potential causes. The study also suggests the need for large prospective studies to adequately assess incidence, risk factors and outcomes.

A model for focal seizure onset, propagation, evolution, and progression.

We developed a neural network model that can account for major elements common to human focal seizures. These include the tonic-clonic transition, slow advance of clinical semiology and corresponding seizure territory expansion, widespread EEG synchronization, and slowing of the ictal rhythm as the seizure approaches termination. These were reproduced by incorporating usage-dependent exhaustion of inhibition in an adaptive neural network that receives global feedback inhibition in addition to local recurrent projections. Our model proposes mechanisms that may underline common EEG seizure onset patterns and status epilepticus, and postulates a role for synaptic plasticity in the emergence of epileptic foci. Complex patterns of seizure activity and bi-stable seizure end-points arise when stochastic noise is included. With the rapid advancement of clinical and experimental tools, we believe that this model can provide a roadmap and potentially an in silico testbed for future explorations of seizure mechanisms and clinical therapies.

Dual mechanisms of ictal high frequency oscillations in human rhythmic onset seizures.

High frequency oscillations (HFOs) are bursts of neural activity in the range of 80 Hz or higher, recorded from intracranial electrodes during epileptiform discharges. HFOs are a proposed biomarker of epileptic brain tissue and may also be useful for seizure forecasting. Despite such clinical utility of HFOs, the spatial context and neuronal activity underlying these local field potential (LFP) events remains unclear. We sought to further understand the neuronal correlates of ictal high frequency LFPs using multielectrode array recordings in the human neocortex and mesial temporal lobe during rhythmic onset seizures. These multiscale recordings capture single cell, multiunit, and LFP activity from the human brain. We compare features of multiunit firing and high frequency LFP from microelectrodes and macroelectrodes during ictal discharges in both the seizure core and penumbra (spatial seizure domains defined by multiunit activity patterns). We report differences in spectral features, unit-local field potential coupling, and information theoretic characteristics of high frequency LFP before and after local seizure invasion. Furthermore, we tie these time-domain differences to spatial domains of seizures, showing that penumbral discharges are more broadly distributed and less useful for seizure localization. These results describe the neuronal and synaptic correlates of two types of pathological HFOs in humans and have important implications for clinical interpretation of rhythmic onset seizures.

Evoked potential monitoring identifies possible neurological injury during positioning for craniotomy.

Somatosensory-evoked potential (SSEP) monitoring is commonly used to detect changes in nerve conduction and prevent impending nerve injury. We present a case series of two patients who had SSEP monitoring for their surgical craniotomy procedure, and who, upon positioning supine with their head tilted 30 degrees-45 degrees, developed unilateral upper extremity SSEP changes. These SSEP changes were reversed when the patients were repositioned. These cases indicate the clinical usefulness of monitoring SSEPs while positioning the patient and adjusting position accordingly to prevent injury.

Anesthetic-specific electroencephalographic patterns during emergence from sevoflurane and isoflurane in infants and children.

BACKGROUND: Devices that monitor the depth of anesthesia are increasingly used to titrate sedation and avoid awareness during anesthesia. Many of these monitors are based upon electroencephalography (EEG) collected from large adult reference populations and not pediatric populations (Anesthesiology, 86, 1997, 836; Journal of Anaesthesia, 92, 2004, 393; Anesthesiology, 99, 2003, 34). We hypothesized that EEG patterns in children would be different from those previously reported in adults and that they would show anesthetic-specific characteristics. METHODS: This prospective observational study was approved by the Institutional Review Board, and informed written consent was obtained. Patients were randomized to receive maintenance anesthesia with isoflurane or sevoflurane. EEG data collection included at least 10 min at steady-state maintenance anesthesia. The EEG was recorded continuously through emergence until after extubation. A mixed model procedure was performed on global and regional power by pooled data analysis and by analyzing each anesthetic group separately. Statistical significance was defined as P < 0.05. RESULTS: Thirty-seven children completed the study (ages 22 days-3.6 years). Isoflurane and sevoflurane had different effects on global and regional EEG power during emergence from anesthesia, and frontal predominance patterns were significantly different between these two anesthetic agents. CONCLUSIONS: The principal finding of the present study was that there are anesthetic-specific and concentration-dependent EEG effects in children. Depth-of-anesthesia monitors that utilize algorithms based on the EEGs of adult reference populations therefore may not be appropriate for use in children.

Focal motor seizures induced by alerting stimuli in critically ill patients.

PURPOSE: We have previously demonstrated that it is common for alerting stimuli to induce electrographic seizures and other periodic or rhythmic patterns in the critically ill; however, only 1 of the first 33 patients we reported with this phenomenon had a detectable clinical correlate. METHODS: Review of charts and video EEG findings in critically ill patients in a neurological ICU at a tertiary care medical center in Manhattan. RESULTS: We identified nine patients who had focal motor seizures repeatedly induced by alerting stimuli. All patients were comatose, and 8/9 had nonconvulsive status epilepticus at some point during their acute illness. Imaging abnormalities involved bilateral thalami in three patients, upper brainstem in one, and the perirolandic region in five. DISCUSSION: We hypothesize that in encephalopathic patients, alerting stimuli activate the arousal circuitry, and, when combined with hyperexcitable cortex, result in epileptiform activity or seizures. This activity can be focal or generalized, and is usually nonconvulsive, as is true of seizures in general in the critically ill. However, when the cortex is hyperexcitable in a specific region only, focal EEG findings arise. If the electrographic seizure activity is adequately synchronized and involves motor pathways, this can present as focal motor seizures, as seen in these nine patients. Alerting can induce seizures in encephalopathic/comatose patients. The observation of clear focal clinical seizures removes the last remaining doubt that these stimulus-induced patterns are indeed seizures by any definition, not simply abnormal arousal patterns.

The Relationship Between Ictal Multi-Unit Activity and the Electrocorticogram.

During neocortical seizures in patients with epilepsy, microelectrode array recordings from the ictal core show a strong correlation between the fast, cellular spiking activities and the low-frequency component of the potential field, reflected in the electrocorticogram (ECoG). Here, we model the relationship between the cellular spike activity and this low-frequency component as the input and output signals of a linear time invariant system. Our approach is based on the observation that this relationship can be characterized by a so-called sinc function, the unit impulse response of an ideal (brick-wall) filter. Accordingly, using a brick-wall filter, we are able to convert ictal cellular spike inputs into an output that significantly correlates with the observed seizure activity in the ECoG (r = 0.40 - 0.56,p < 0.01) , while ECoG recordings of subsequent seizures within patients also show significant, but lower, correlations (r = 0.10 - 0.30,p < 0.01) . Furthermore, we can produce seizure-like output signals using synthetic spike trains with ictal properties. We propose a possible physiological mechanism to explain the observed properties associated with an ideal filter, and discuss the potential use of our approach for the evaluation of anticonvulsant strategies.

Prognosis of Significant Intraoperative Neurophysiologic Monitoring Events in Severe Spinal Deformity Surgery.

BACKGROUND: Intraoperative neurophysiologic monitoring has become a standard tool for mitigating neurologic injury during spinal deformity surgery. Significant monitoring changes during deformity correction are relatively uncommon. This study characterizes precipitating factors for neurologic injury and relates significant events and postoperative neurologic prognosis. METHODS: All spinal deformity surgeries at a West African hospital over a 12-month period were reviewed. Patients were included if complete operative reports, monitoring data, and postoperative neurologic examinations were available for review. Surgical and systemic triggers of monitoring events were recorded and neurologic status was followed for 6 weeks postoperatively. RESULTS: Eighty-eight patients met inclusion criteria. The average age was 14 years (3-28). The average kyphosis was 108° (54°-176°) and average scoliosis was 100° (48°-177°). There were 44 separate neurologic events in 34 patients (39%). The most common triggers were traction or positioning (16), posterior column osteotomies/vertebral column resections (9/1), and distraction, corrective maneuvers, or implant placement (12). On surgery completion, 100% (12/12) of events from non-osteotomy-related surgical procedures, 75% (12/16) of events from traction or positioning resolved; however, 0% (0/10) of events from osteotomies resolved completely. Eight percent (7/88) had new neurologic deficits postoperatively, all with intraoperative monitoring changes. In 6 of these 7 patients, the event was attributed to an osteotomy; in 1 patient the cause was not determined. At 6-week follow-up, all patients had some preserved motor function bilaterally with the ability to walk (ASIA D/E) or recovered completely. CONCLUSIONS: Intraoperative signal changes were most frequently from traction or positioning. However, the most common cause of persistent neurologic deterioration and the only cause of postoperative neurologic deficit was the performance of osteotomies. Unlike traction- or instrument-related correction, osteotomies produce irreversible changes, from canal intrusion or sudden localized deformity change. The incidence of postoperative neurologic deficit is very low when the inciting cause is reversed; however, osteotomy-related events are irreversible, with a high incidence of associated lasting neurologic injury.

A randomized crossover study of the effects of lidocaine on motor- and sensory-evoked potentials during spinal surgery.

BACKGROUND CONTEXT: Lidocaine has emerged as a useful adjuvant anesthetic agent for cases requiring intraoperative monitoring of motor-evoked potentials (MEPs) and somatosensory-evoked potentials (SSEPs). A previous retrospective study suggested that lidocaine could be used as a component of propofol-based intravenous anesthesia without adversely affecting MEP or SSEP monitoring, but did not address the effect of the addition of lidocaine on the MEP and SSEP signals of individual patients. PURPOSE: The purpose of this study was to examine the intrapatient effects of the addition of lidocaine to balanced anesthesia on MEPs and SSEPs during multilevel posterior spinal fusion. STUDY DESIGN: This is a prospective, two-treatment, two-period crossover randomized controlled trial with a blinded primary outcome assessment. PATIENT SAMPLE: Forty patients undergoing multilevel posterior spinal fusion were studied. OUTCOME MEASURES: The primary outcome measures were MEP voltage thresholds and SSEP amplitudes. Secondary outcome measures included isoflurane concentrations and hemodynamic parameters. METHODS: Each participant received two anesthetic treatments (propofol 50 mcg/kg/h and propofol 25 mcg/kg/h+lidocaine 1 mg/kg/h) along with isoflurane, ketamine, and diazepam. In this manner, each patient served as his or her own control. The order of administration of the two treatments was determined randomly. RESULTS: There were no significant within-patient differences between MEP threshold voltages or SSEP amplitudes during the two anesthetic treatments. CONCLUSIONS: Lidocaine may be used as a component of balanced anesthesia during multilevel spinal fusions without adversely affecting the monitoring of SSEPs or MEPs in individual patients.

Frequency and predictors of nonconvulsive seizures during continuous electroencephalographic monitoring in critically ill children.

OBJECTIVE: To determine the incidence, predictors, and timing of nonconvulsive seizures (NCSz) during continuous electroencephalographic monitoring (cEEG) in critically ill children. METHODS: We identified critically ill children who underwent cEEG during a 4-year period. Multivariate logistic regression analysis was performed to determine variables associated with NCSz. RESULTS: Among 117 monitored children, 44% had seizures on cEEG and 39% had NCSz. The majority of patients with seizures (75%) had purely NCSz, and 23% of patients had status epilepticus, which was purely nonconvulsive in 89% of cases. Seizures occurred immediately on cEEG initiation in 15%, within 1 hour in 50%, and within 24 hours in 80%. Those with clinical seizures prior to cEEG were more likely to have NCSz on cEEG (83%) than those without prior seizures (17%). On multivariate analysis, NCSz were associated with periodic lateralized epileptiform discharges and absence of background reactivity. CONCLUSIONS: Seizures, the majority being NCSz, are common during cEEG in critically ill children (seen in 44% of patients). Half are detected in the first hour of recording, whereas 20% are not detected until after more than 24 hours of recording. Nonconvulsive seizures are associated with periodic lateralized epileptiform discharges and absence of reactivity on cEEG. This study confirms the importance of prolonged cEEG for critically ill children as a means to detect NCSz.

The ictal wavefront is the spatiotemporal source of discharges during spontaneous human seizures.

The extensive distribution and simultaneous termination of seizures across cortical areas has led to the hypothesis that seizures are caused by large-scale coordinated networks spanning these areas. This view, however, is difficult to reconcile with most proposed mechanisms of seizure spread and termination, which operate on a cellular scale. We hypothesize that seizures evolve into self-organized structures wherein a small seizing territory projects high-intensity electrical signals over a broad cortical area. Here we investigate human seizures on both small and large electrophysiological scales. We show that the migrating edge of the seizing territory is the source of travelling waves of synaptic activity into adjacent cortical areas. As the seizure progresses, slow dynamics in induced activity from these waves indicate a weakening and eventual failure of their source. These observations support a parsimonious theory for how large-scale evolution and termination of seizures are driven from a small, migrating cortical area.