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A 43-year-old man with bihemispheric periventricular nodular heterotopia had medically intractable multifocal epilepsy and seizure-related falls. Video-EEG recorded a seizure with ictal asystole, EEG attenuation, and loss of postural tone, reflective of cerebral hypoperfusion (figure 1). After pacemaker implantation, EEG recorded a seizure with ictal cardiac pacing, without EEG attenuation (figure 2). His falls resolved. Antiseizure medications and epilepsy surgery can control seizures and ictal asystole.1 For individuals with intractable epilepsy and ictal asystole who are poor surgical candidates, pacemaker implantation is indicated to prevent injury and any potential contribution of ictal asystole in sudden unexpected death in epilepsy.1,2

SUMMARY Although interictal spikes (IISs) are a well-established EEG biomarker for epilepsy, whether they are also a biomarker of cognitive deficits is unclear. Interictal spikes are dynamic events consisting of a synchronous discharge of neurons producing high frequency oscillations and a succession of action potentials which disrupt the ongoing neural activity. There are robust data showing that IISs result in transitory cognitive impairment with the type of deficit specific to the cognitive task and anatomic location of the IIS. Interictal spike, particularly if frequent and widespread, can impair cognitive abilities, through interference with waking learning and memory and memory consolidation during sleep. Interictal spikes seem to be particularly concerning in the developing brain where animal data suggest that IISs can lead to adverse cognitive effects even after the disappearance of the spikes. Whether a similar phenomenon occurs in human beings is unclear. Thus, although IISs are a clear biomarker of transitory cognitive impairment, currently, they lack sensitivity and specificity as a biomarker for enduring cognitive impairment.

SUMMARY In patients with mesial temporal lobe epilepsy, high-frequency, low-amplitude electrical stimulation (ES) was applied during 3 weeks through contacts of intracranial electrodes that defined the epileptogenic zone. This subacute ES induced cessation of spontaneous seizures, decreased the number of EEG interictal spikes, caused a 10-fold increase in threshold to induce postdischarges, and showed a profound decrease in regional blood flow of the stimulated area in SPECT studies. Autoradiography analysis of surgical specimens from these patients demonstrated increased expression of benzodiazepine receptors and in gamma-aminobutyric acid content, particularly in the parahippocampal cortex. These observations provided evidence of a gamma-aminobutyric acid-mediated antiepileptic effect induced by ES. Several reports of long-term hippocampal ES through internalized neurostimulators have confirmed the antiepileptic effect on mesial temporal lobe-initiated seizures, with preservation of neuropsychological performance, in particular memory functions. The experience of the authors is that the response is optimal in patients without hippocampal sclerosis evidenced by MRI, whereas it is less significant and delayed in patients with hippocampal sclerosis. Other studies reported the best result stimulating through the contacts in the subiculum, the transition between the hippocampus and parahippocampal cortex, that usually escapes to the hippocampal sclerosis. Currently, the effect of ES directed at the subiculum and the parahippocampal cortex in patients with hippocampal sclerosis is under investigation.

PURPOSE: We evaluated interictal discharges (IEDs) as a biomarker for the time to development of electrographic seizures (ES). METHODS: Prospective observational study of 254 critically ill children who underwent continuous electroencephalography (cEEG) monitoring. We excluded neonates and patients with known epilepsy or the sole cEEG indication to characterize events. Interictal discharges included sporadic epileptiform discharges and periodic and rhythmic patterns. Sporadic epileptiform discharges were categorized as low frequency (rare [

Purpose Epileptiform activity limited to deep sources such as the hippocampus currently lacks reliable scalp correlates. Recent studies, however, have found that a subset of hippocampal interictal discharges may be associated with visible scalp signals, suggesting that some types of hippocampal activity may be monitored noninvasively. The purpose of this study is to characterize the relationship between these scalp waveforms and the underlying intracranial activity. Methods Paired intracranial and scalp EEG recordings obtained from 16 patients were used to identify hippocampal interictal discharges. Discharges were grouped by waveform shape, and spike-triggered averages of the intracranial and scalp signals were calculated for each group. Cross-correlation of intracranial and scalp spike-triggered averages was used to determine their temporal relationship, and topographic maps of the scalp were generated for each group. Results Cross-correlation of intracranial and scalp correlates resulted in two classes of scalp waveforms-those with and without time delays from the associated hippocampal discharges. Scalp signals with no delay showed topographies with a broad field with higher amplitudes on the side ipsilateral to the discharges and a left-right flip in polarity-observations consistent with the volume conduction of a single unilateral deep source. In contrast, scalp correlates with time lags showed rotational dynamics, suggesting synaptic propagation mechanisms. Conclusions The temporal relationship between the intracranial and scalp signals suggests that both volume conduction and synaptic propagation contribute to these scalp manifestations. Furthermore, the topographic evolution of these scalp waveforms may be used to distinguish spikes that are limited to the hippocampus from those that travel to or engage other brain areas.

SUMMARY Periodic discharges seen in patients undergoing continuous EEG pose a challenge to physicians in falling into the interictal-ictal continuum and need for appropriate diagnostic and management approach. The authors herein present an 83-year-old male patient with an acute subdural hematoma who developed intermittent right upper and lower extremity weakness with change in mental status post craniotomy and hematoma evacuation. The patient was intubated and sedated with midazolam and propofol and placed on anti-seizure medications to control seizures. He was placed on continuous EEG monitoring and later developed lateralized periodic discharges. To guide treatment, a computed tomography perfusion study of the brain was performed. The results were consistent with an ictal phenomenon because of the presence of left hemispheric hyperemia. This increased cerebral blood volume and blood flow was used as a diagnostic tool to warrant more aggressive antiepileptic regimen. The patient was then started on an additional anti-seizure medication and dosages were further optimized. This led to an improvement in the patient's EEG and clinical state. There are numerous studies that show lateralized periodic discharges are seen as examples of subclinical status epilepticus and demonstrate hypermetabolism and hyperemia on positron emission tomography and single-photon emission computed tomography scans. When such imaging modalities are unavailable, cortical hyperperfusion on a computed tomography perfusion study might be a valid predictor of ongoing, subclinical, ictal activity and may be used as a complementary diagnostic tool to EEG to guide treatment.

INTRODUCTION: Spatial patterns of long-range seizure propagation in epileptic networks have not been well characterized. Here, we use ictal high gamma activity as a proxy of intense neuronal population firing to map the spatial evolution of seizure recruitment. METHODS: Ictal high gamma activity (80–150 Hz) was analyzed in 13 patients with 72 seizures recorded by stereotactic depth electrodes, using previously validated methods. Distinct spatial clusters of channels with the ictal high gamma signature were identified, and seizure hubs defined as stereotypically recruited non-overlapping clusters. Clusters were correlated with asynchronous seizure terminations to provide supportive evidence for independent seizure activity at these sites. The spatial overlap between seizure hubs and interictal ripples was compared. RESULTS: Ictal high gamma activity was detected in 71% of seizures and 10% of implanted contacts, enabling tracking of contiguous and noncontiguous seizure recruitment. Multiple seizure hubs were identified in 54% of cases, including 43% of patients thought preoperatively to have unifocal epilepsy. Noncontiguous recruitment was associated with asynchronous seizure termination (Odds ratio=19.7, p=0.029). Interictal ripples demonstrated greater spatial overlap with ictal high gamma activity in cases with single seizure hubs compared to those with multiple hubs (100% vs 66% per patient, p=0.03). CONCLUSIONS: Ictal high gamma activity may serve as a useful adjunctive biomarker to distinguish contiguous seizure spread from propagation to remote seizure sites. High gamma sites were found to cluster in stereotyped seizure hubs rather than being broadly distributed. Multiple hubs were common even in cases that were considered unifocal.

Purpose of review The increased identification of seizures with insular ictal onset, promoted by the international development of stereo-electroencephalography (SEEG), has led to the recent description of larger cohorts of patients with insular or insulo-opercular epilepsies than those previously available. These new series have consolidated and extended our knowledge of the rich ictal semiology and diverse anatomo-clinical correlations that characterized insular seizures. In parallel, some experiences have been gained in the surgical treatment of insular epilepsies using minimal invasive procedures. Recent findings The large majority of patients present with auras (mostly somatosensory and laryngeal) and motor signs (predominantly elementary and orofacial), an underlying focal cortical dysplasia, and an excellent postoperative seizure outcome. Many other subjective and objective ictal signs, known to occur in other forms of epilepsies, are also observed and clustered in five patterns, reflecting the functional anatomy of the insula and its overlying opercula, as well as preferential propagation pathways to frontal or temporal brain regions. A nocturnal predominance of seizure is frequently reported, whereas secondary generalization is infrequent. Some rare ictal signs are highly suggestive of an insular origin, including somatic pain, reflex seizures, choking spells, and vomiting. Minimal invasive surgical techniques have been applied to the treatment of insular epilepsies, including Magnetic Resonance Imaging-guided laser ablation (laser interstitial thermal therapy (LITT)), radiofrequency thermocoagulation (RFTC), gamma knife radiosurgery, and responsive neurostimulation. Rates of seizure freedom (about 50%) appear lower than that reported with open-surgery (about 80%) with yet a significant proportion of transient neurological deficit for LITT and RFTC. Summary Significant progress has been made in the identification and surgical treatment of insular and insulo-opercular epilepsies, including more precise anatomo-clinical correlations to optimally plan SEEG investigations, and experience in using minimal invasive surgery to reduce peri-operative morbidity.

ObjectiveTo analyze the association between peri-ictal brainstem posturing semiologies with postictal generalized electroencephalographic suppression (PGES) and breathing dysfunction in generalized convulsive seizures (GCS).MethodsIn this prospective, multicenter analysis of GCS, ictal brainstem semiology was classified as (1) decerebration (bilateral symmetric tonic arm extension), (2) decortication (bilateral symmetric tonic arm flexion only), (3) hemi-decerebration (unilateral tonic arm extension with contralateral flexion) and (4) absence of ictal tonic phase. Postictal posturing was also assessed. Respiration was monitored with thoracoabdominal belts, video, and pulse oximetry.ResultsTwo hundred ninety-five seizures (180 patients) were analyzed. Ictal decerebration was observed in 122 of 295 (41.4%), decortication in 47 of 295 (15.9%), and hemi-decerebration in 28 of 295 (9.5%) seizures. Tonic phase was absent in 98 of 295 (33.2%) seizures. Postictal posturing occurred in 18 of 295 (6.1%) seizures. PGES risk increased with ictal decerebration (odds ratio [OR] 14.79, 95% confidence interval [CI] 6.18–35.39,p< 0.001), decortication (OR 11.26, 95% CI 2.96–42.93,p< 0.001), or hemi-decerebration (OR 48.56, 95% CI 6.07–388.78,p< 0.001). Ictal decerebration was associated with longer PGES (p= 0.011). Postictal posturing was associated with postconvulsive central apnea (PCCA) (p= 0.004), longer hypoxemia (p< 0.001), and Spo2recovery (p= 0.035).ConclusionsIctal brainstem semiology is associated with increased PGES risk. Ictal decerebration is associated with longer PGES. Postictal posturing is associated with a 6-fold increased risk of PCCA, longer hypoxemia, and Spo2recovery. Peri-ictal brainstem posturing may be a surrogate biomarker for GCS severity identifiable without in-hospital monitoring.Classification of EvidenceThis study provides Class III evidence that peri-ictal brainstem posturing is associated with the GCS with more prolonged PGES and more severe breathing dysfunction.

Purpose To study if one can conceptualize the scalp ictal onset pattern through analysis of interictal spike domain analysis in temporal lobe epilepsy (TLE). Methods Seventy-four patients with unilateral mesial temporal sclerosis (MTS) were categorized into "type A" interictal epileptiform discharges (IEDs) with negativity over infero-lateral scalp electrodes over temporal region and contralateral central region showing positivity; all IEDs other than type A were categorized as type B. The ictal electrographic patterns was termed "focal" when confined to side of MTS, was "regional" when lateralized to the ipsilateral hemisphere; "diffuse" if nonlateralized/localized; and ictal onset contralateral to MTS termed as "discordant." Results A total of 377 seizures and 5,476 spikes were studied. These were divided into four types: (1) type A IEDs ipsilateral to MTS (44 patients), (2) type A IEDs bitemporally (16 patients), (3) type A IEDs contralaterally (7 patients) and type B IEDs ipsilaterally, and (4) bilateral type B IEDs (7 patients). The ictal pattern was either focal or regional in 51 of 60 patients (85%) with type A IEDs; it was "diffuse" in 9 patients (15%). Diffuse ictal onset was seen in 12 of 14 (86%) with either ipsilateral/bitemporal type B IEDs. Ictal onset on the opposite hemisphere was noted in 2 (14%). Conclusions Type A IEDs signify a focal ictal onset and type B IEDs suggest a diffuse ictal onset in patients with MTS on one side. Significance Interictal spike domain analysis helps predicting ictal patterns in temporal lobe epilepsy.

A common experimental neurophysiological method to study synaptic plasticity is pairing activity of somatosensory afferents and motor cortical circuits, so-called paired associative stimulation (PAS). Dysfunctional inhibitory and excitatory PAS mechanisms within the sensorimotor system were described in patients with migraine without aura (MO) between attacks. We have recently observed that the same bidirectional PAS rules also apply to the visual system. Here, we have tested whether dysfunctioning associative plasticity might characterize the visual system of patients with MO. In 14 patients with MO between attacks and in 15 healthy volunteers, we performed a previously validated visual PAS (vPAS) protocol by coupling 90 black-and-white checkerboard reversals with low-frequency transcranial magnetic stimulation pulses over the occipital cortex at 2 interstimulus intervals of -25/+25 ms around the visual-evoked potential (VEP) P1 latency. We recorded VEPs (600 sweeps) before, immediately after, and 10 min after each vPAS session. We analysed VEP N1-P1 amplitude and delayed habituation. Although vPAS-25 significantly enhanced and vPAS + 25 reduced VEP amplitude habituation in healthy volunteers, the same protocols did not significantly change VEP amplitude habituation in MO between attacks. We provide evidence for lack of habituation enhancing and habituation suppressing visual PAS mechanisms within the visual system in interictal migraine. This finding, in combination with those previously obtained studying the sensorimotor system, leads us to argue that migraine disease-related dysrhythmic thalamocortical activity prevents the occurrence of physiological bidirectional synaptic plasticity induced by vPAS.

The use of continuous EEG monitoring has expanded in the last decade, allowing the recognition not only of nonconvulsive seizures but also of the relatively high prevalence of periodic and rhythmic EEG patterns. Periodic discharges are a fairly common EEG pattern and often present a therapeutic challenge when encountered. We will consider five associations of these periodic discharges: ictal, acute seizures, epileptogenic, injurious, and epiphenomenal. We present the challenges and unanswered questions pertaining to periodic discharges, along with several next steps and future directions to help enhance our understanding of periodic discharges. We also present an algorithmic approach to management centered on clinicoelectrographic and clinicoradiologic data.

ObjectiveTo test the hypothesis that absence seizures can evolve to generalized tonic-clonic seizures, we documented electroclinical features of this novel seizure type.MethodsIn 4 large video-EEG databases, we identified recordings of seizures starting with impaired awareness that, without returning to baseline interictal state, evolved to generalized tonic-clonic seizures. We extracted the detailed semiologic and electrographic characteristics of these seizures, and we documented the clinical background, diagnoses, and therapeutic responses in these patients.ResultsWe identified 12 seizures from 12 patients. All seizures started with a period of impaired awareness and bursts of generalized spike or polyspike and slow-wave discharges, the hallmark of absence seizures. Without returning to baseline, the nonmotor (absence) phase was followed by tonic-clonic convulsions. We called this novel generalized seizure type absence-to-bilateral-tonic-clonic seizure. Most patients had idiopathic generalized epilepsies, although with a high incidence of unusual features and poor therapeutic response.ConclusionsAbsence-to-bilateral-tonic-clonic seizures are a novel generalized seizure type. Clinicians should be aware of this seizure for correctly diagnosing patients. This novel seizure type may further elucidate generalized ictogenesis.

OBJECTIVE Localization of epileptogenic focus in drug-refractory epilepsy using Tc-99m ethylene cystine dimer (ECD) brain single photon emission computed tomography (SPECT) is less studied in patients with discordant findings on video electroencephalogram (VEEG) and MRI. The study was done to evaluate brain SPECT for epileptogenic focus localization and postoperative seizure freedom. METHODS Epilepsy patients with discordant VEEG and MRI findings underwent brain SPECT at ictal and interictal phases. Various groups unilateral/bilateral mesial temporal sclerosis (MTS), solitary and multifocal lesional, nonlesional epilepsy were studied for localization of epileptogenic focus and postoperative seizure freedom (>2 years) using Engels classification. Reasons for nonoperability was evaluated in nonoperated group. RESULTS SPECT could localize epileptogenic focus in 49/67 (73.13%) and guided surgery in 19/33 (57.57%) patients in operated group. SPECT was useful in 12 (46.12%) of unilateral (2)/bilateral (10) MTS. Postoperative seizure freedom of Engels Class I and II in 22 (66.67%), III in six (18.2%) and IV in one patient based on SPECT findings (P = 0.0086). Overall sensitivity and specificity were 79.3% and 85.7%, respectively. SPECT could localize epileptogenic focus in 23/34 (67.64%) patients in nonoperated group; 10 (29.41%) patients refused for surgery and no epileptogenic focus was localized in the rest of 14 (41.2%). CONCLUSION Ictal SPECT showed incremental value and was found necessary for epileptogenic focus localization and subsequent surgery in unilateral/bilateral MTS in this study. Seizure freedom in patients undergoing epilepsy surgery based on ictal SPECT assistance was comparable to the surgical group not requiring ictal SPECT.

Seizures and interictal epileptiform discharges (IEDs) have been described during sevoflurane. We prospectively estimated their incidence in 54 otherwise neurologically healthy infants by obtaining the full-head video electroencephalogram (EEG). No infants had clinical seizures, but 1 had an electrographic seizure; 3 others had focal IEDs (7.4%; 95% confidence interval [CI], 2.1%-17.9%). We detected no differences in demographic or clinical characteristics between normal and abnormal EEG groups. Diffuse slowing was the most common initial EEG change followed by fast (α, β) activity in all head leads. Larger studies with more statistical power are needed to further investigate the hypotheses generated with this research.

Purpose The clinical significance of magnetoencephalography (MEG) dipole clusters in the insular region in patients with focal epilepsy, when present in conjunction with MEG dipole clusters in other regions of the brain is not known. Methods All patients (adult and pediatric) with MEG dipole clusters involving the insula were retrospectively evaluated. Patients who underwent any form of surgical intervention were included in the study. Data obtained included age, sex, seizure characteristics, MRI brain, EEG, MEG, intracranial EEG, type of intervention, and seizure outcomes. Results Twenty-four patients (12 adults and 12 pediatric) were included. Eight patients had one staged intervention and 16 had intracranial evaluation. Ten of 11 patients (91%) with insular coverage by stereotactic EEG had interictal insular spikes, and 5 of 11 patients (45%) had ictal onset from the insula. Combined Engel (I & II) outcomes were seen in five patients with resections/ablations involving the insula MEG dipole clusters as compared with eight patients where the insular MEG dipole clusters were not resected/ablated. Conclusions Insular MEG dipole clusters identified on surface MEG correlated with interictal spikes in intracranial stereotactic electrode contacts in the insula. The presence of insular MEG dipole clusters, however, does not definitively imply a primary insular onset epilepsy.

Introduction Subclinical rhythmic EEG discharges in adults (SREDA) is a very rare benign EEG pattern. The electrophysiological features and atypical variants of SREDA has wide spectrum and they are poorly known. It resembles ictal discharges, and overinterpretation of SREDA may lead to misdiagnosis of epilepsy. Herein, we aimed to report patients with SREDA to identify the frequency and characterized clinical, demographic, electrophysiological features. Methods We reviewed 22,234 EEG reports that are reported by the same experienced clinical neurophysiologists, between 2012 and 2018. The EEGs with SREDA were reevaluated blindly by three clinical neurophysiologists. The demographic, clinical characteristics, and neuroimaging features of the patients were reviewed. Results Subclinical rhythmic EEG discharges in adults was present in 14 EEG records (0.06%), in nine patients. The mean age of patients was 52.1 ± 17.7 (range, 21-71) years. The patients had been diagnosed with several neurologic diseases, including cerebrovascular disease, epilepsy, psychogenic nonepileptic seizures, mental retardation, Alzheimer disease, and transient global amnesia. One patient had unilateral lesion, in whom SREDA had appeared on contralateral side of the lesion, whereas other patients with normal or nonlateralized lesions had SREDA bilaterally and symmetrical. This variant had been misdiagnosed as an ictal discharge in previous EEGs in three patients. Conclusions This study indicates that SREDA is difficult to associate with any specific condition. The pathophysiology of SREDA can not be explained by a single mechanism. Even if it is mostly observed in older adults, it is also observed in young adults in this study. It is important to differentiate SREDA from ictal discharge to prevent misdiagnosis of epilepsy especially in nonepileptic paroxysmal events.

PURPOSE OF REVIEW Epilepsy is a dynamical disorder of the brain characterized by sudden, seemingly unpredictable transitions to the ictal state. When and how these transitions occur remain unresolved questions in neurology. RECENT FINDINGS Modelling work based on dynamical systems theory proposed that a slow control parameter is necessary to explain the transition between interictal and ictal states. Recently, converging evidence from chronic EEG datasets unravelled the existence of cycles of epileptic brain activity at multiple timescales - circadian, multidien (over multiple days) and circannual - which could reflect cyclical changes in a slow control parameter. This temporal structure of epilepsy has theoretical implications and argues against the conception of seizures as completely random events. The practical significance of cycles in epilepsy is highlighted by their predictive value in computational models for seizure forecasting. SUMMARY The canonical randomness of seizures is being reconsidered in light of cycles of brain activity discovered through chronic EEG. This paradigm shift motivates development of next-generation devices to track more closely fluctuations in epileptic brain activity that determine time-varying seizure risk.

Some epileptic spasms are classified into focal-onset seizures. However, the cortical network underlying this kind of spasm seizure is not yet clear. Four patients with epileptic spasms who underwent intracranial electrode implantation and focal resection surgery were studied. All the patients had good outcomes, and three of them with intellectual disability showed improved intelligence after surgery. The power spectra characteristics of electrocorticography and the dynamic functional network changes of epileptic spasms were investigated. Electrocorticography power in the resected zone peaked 0.5 seconds before the clinical seizure onset and was especially prominent in the γ and ripple bands. The functional network analysis showed particular dynamic patterns of high-frequency activity among the resected zone, sensorimotor cortex, and the other region. In the gamma band, during the interictal segment, the information flow from the resected zone and the other region to the sensorimotor cortex was prominent. During the preictal segment, the information flow from the resected zone and sensorimotor cortex to the other region became stronger. In the ripple band, during the interictal segment, the information flow from the resected zone to the sensorimotor cortex and the other region was high. During the preictal segment, the information flow between the resected zone and sensorimotor cortex became stronger. Our results suggest that the sensorimotor cortex is a requisite for spasm seizure initiation, and the ripple activity loop between the resected zone and sensorimotor cortex may give rise to the seizure onset with the help of the gamma activity loop between the sensorimotor cortex and the other region for activation spreading.

Herein, the authors report for the first time, scalp-recorded (1) focal ictal direct current (DC) shifts (active DC shifts; that precede conventional pattern) from the chronic focus of focal epilepsy and (2) ictal high-frequency oscillation after ictal DC shifts (passive DC shifts; that follow both conventional and high-frequency oscillation ictal patterns) from the acute focus of acute symptomatic seizures (Szs) in a 77-year-old man. Sixteen episodes of clinical Szs were recorded by scalp EEG with a 2-seconds time constant. Among the 16 recorded episodes of Sz, four EEG Sz patterns originated from the left posterior temporal area (chronic focus), and all patterns (100%) exhibited active DC shifts preceding the conventional pattern by 12 seconds. Twelve EEG Sz patterns originated from the right parietal area (acute focus), and the high-frequency oscillations (five Szs) (41.6%) and DC shifts (six Szs) (50%) occurred first, followed by the conventional pattern 8 seconds later. Because both the active and the passive DC shifts were recorded with a time constant of 2 seconds, which was smaller than that reported previously for ictal DC shifts (e.g., time constant of 10 seconds), clinically useful ictal DC shifts could be routinely inspected with a time constant of 2 seconds.

Copyright © 2020 by the American Clinical Neurophysiology Society, Purpose: Periodic discharges (PDs) are common in acute structural or metabolic brain lesions, but their occurrence during follow-up of epileptic patients in an outpatient setting is rare. Aim of this article was to study whether PDs on the routine outpatient scalp EEG of patients with epilepsy, as compared with nonperiodic epileptiform discharges, are associated with drug refractoriness and the decompensation of epilepsy and particular etiologies. Methods: A retrospective case–control study. EEG reports were screened for PDs and their variants. The inclusion criteria were as follows: a diagnosis of epilepsy, epileptogenic lesion on imaging, or a normal 3-T MRI. Inpatient EEGs or EEGs performed in patients with acute cerebral lesions were excluded. Age- and sex-matched controls presenting with other epileptiform EEG abnormalities were selected, and similar selection criteria were applied. Results: Forty-one patients with PDs and 82 controls were selected. There were no significant differences between the cases and controls in the rates of epilepsy decompensation at the time of EEG collection or drug refractoriness. Stroke, hippocampal sclerosis, and malformations of cortical development were the most frequent etiologies, without significant differences between the groups. Conclusions: By performing a case–control study, the authors have shown that PDs are not a marker of epilepsy decompensation and drug refractoriness and that the finding of PDs is not suggestive of particular epilepsy etiologies, when compared with other epileptiform abnormalities.

Purpose Electrical source imaging may yield ambiguous results in multilesional epilepsy. The aim of this study was to test the clinical utility of lesion-constrained electrical source imaging in epilepsy surgery in children with tuberous sclerosis complex. Methods Lesion-constrained electrical source imaging is a novel method based on a proposed head model in which the source solution is constrained to lesions. Using a goodness of fit analysis, we rank-ordered individual tubers by their ability to approximate interictal and ictal EEG data. The overlap with the surgical resection cavity was determined qualitatively, and placed findings in the context of epilepsy surgical outcome, and compared with the low-resolution brain electromagnetic tomography solution. Results Low-resolution brain electromagnetic tomography predicted the surgical cavity in only one patient with good outcome (true positive) and localized to outside of the cavity in two patients with a good outcome (false negative). In one patient with a poor outcome, the interictal low-resolution brain electromagnetic tomography solution overlapped with the cavity (false positive). Lesion-constrained electrical source imaging of ictal EEG data identified tubers concordant with the resection zone in three patients with a good surgical outcome (true positive) and appropriately discordant in three other patients with a poor outcome (true negative). Conclusions Lesion-constrained electrical source imaging on low-resolution EEG data provides complementary information in the presurgical workup for patients with tuberous sclerosis complex, although further validation is required. In the appropriate clinical context, the yield of source localization on low-resolution EEG data may be increased by reduction of the solution space.

The correlation of clinical semiology with neuronal firing in human seizures has not been well described. Similarly, the neuronal firing patterns underlying high-frequency oscillations during seizures remain controversial. Using implanted subdural electrodes and a microelectrode array in a patient with focal status epilepticus, in which 40 habitual focal motor seizures and 101 subclinical seizures were captured, the authors analyzed the association of EEG, high-frequency oscillations, and multiunit activity to facial motor semiology. The development of ictal high-frequency oscillations in subdural electrodes overlying face motor cortex was temporally associated with clonic facial movements. In representative seizures selected for multiunit analysis, synchronization of neuronal firing in the adjacent microelectrode array aligned with clinical onset and was greater in clinical seizures compared with subclinical seizures. This report demonstrates the electrophysiologic signatures of focal seizures at the level of neuronal firing, high-frequency oscillations, and EEG as they organize from microscale to macroscale, with clinical correlation.

Purpose Magnetoencephalography (MEG) is a noninvasive tool used clinically for presurgical evaluation of patients with medically intractable epilepsy. These recordings require patients to lie still for prolonged periods of time in a magnetically shielded room. Children or uncooperative adults with epilepsy may require sedation to reduce movement artefact and obtain high-quality recordings. Potential challenges related to the use of total intravenous anesthesia in the MEG environment include limited access to the patient's airway, remote location, suppression of cortical activity, and increased patient care expenses. We report our experience with intranasal dexmedetomidine as sedation for intractable epilepsy patients undergoing MEG. Methods Sleep deprivation occurred the night before MEG testing. Intranasal dexmedetomidine (2 μg/kg) was administered and oxygen saturation, blood pressure, and pulse rate were recorded continuously on a monitor outside the magnetically shielded room. A recording of spontaneous neuromagnetic activity was immediately followed by median nerve electrical stimulation. Results Twenty-six patients (mean age 12.2 ± 4.2 years) with medically intractable epilepsy were recorded using this protocol. There were no failures of sedation, and although patients experienced transient bradycardia, none required intervention and the recording did not need to be stopped. In all cases, artefact-free MEG recordings were obtained with sufficient interictal discharges available for source analysis. Conclusions Our experience suggests that intranasal dexmedetomidine is an advantageous sedation option for children and adults with intractable epilepsy who are undergoing MEG. Further research is needed to determine the best ways to apply these methods to younger children and those with developmental disabilities.

Migraine headache is an episodic phenomenon, and patients with episodic migraine have ictal (headache), peri-ictal (premonitory, aura, and postdrome), and interictal (asymptomatic) phases. We aimed to find the functional characteristics of the migraine brain regardless of headache phase using dynamic functional connectivity analysis. We prospectively recruited 50 patients with migraine and 50 age- and sex-matched controls. All subjects underwent a resting-state functional magnetic resonance imaging. Significant networks were defined in a data-driven fashion from the interictal (48 hours apart from headache phases) patients and matched controls (interictal data set) and tested to ictal or peri-ictal patients and controls (ictal/peri-ictal data set). Both static and dynamic analyses were used for the between-group comparison. A false discovery rate correction was performed. As a result, the static analysis did not reveal a network which was significant in both interictal and ictal/peri-ictal data sets. Dynamic analysis revealed significant between-group differences in 7 brain networks in the interictal data set, among which a frontoparietal network (controlspatients, P = 0.0467), 2 brainstem networks (patientscontrols, P = 0.0467 and0.001), and a cerebellar network (controlspatients, P = 0.0408 and0.001 in 2 states) remained significant in the ictal/peri-ictal data set. Using these networks, migraine was classified with a sensitivity of 0.70 and specificity of 0.76 in the ictal/peri-ictal data set. In conclusion, the dynamic connectivity analysis revealed more functional networks related to migraine than the conventional static analysis, suggesting a substantial temporal fluctuation in functional characteristics. Our data also revealed migraine-related networks which show significant difference regardless of headache phases between patients and controls.

PURPOSE OF REVIEW Imaging constitutes one of the key pillars in the diagnostic workup after a first seizure as well as for the presurgical workup in epilepsy. The role of imaging in emergency situations, mainly to support the adequate diagnosis, as well as its role in planning of noninvasive image-guided therapies is less well established. Here, we provide an overview on peri-ictal imaging findings to support differential diagnosis in emergency situations and describe recent attempts toward minimal invasive therapy in the treatment of epilepsy and its comorbidities based on a combination of imaging techniques with ultrasound. RECENT FINDINGS Peri-ictal perfusion changes can differentiate ictal stroke mimics from acute ischemic stroke if focal areas of increased perfusion are depicted by computed tomography or MRI. Postictal perfusion patterns in patients with persisting neurological symptoms are frequently normal and do not reach enough diagnostic sensitivity to differentiate between stroke and its mimics. Noninvasive magnetic resonance-techniques as arterial spin labeling may provide a higher sensitivity, especially in combination with diffusion-weighted and susceptibility-weighted MRI. Imaging guided focused ultrasound (FUS) bears the potential to ablate epileptogenic tissue and allows suppression of epileptic activity. Imaging guided blood-brain-barrier opening with FUS offers new options for local drug administration. SUMMARY MRI should be considered the method of choice in the differential diagnosis of peri-ictal imaging findings and their differential diagnosis. A combination of various MRI techniques with FUS opens new avenues for treatment of epilepsy.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.

Errors in diagnosis are relatively common in medicine and occur in all specialties. The consequences can be serious for both patients and physicians. Errors in neurology are often because of the overemphasis on 'tests' over the clinical picture. The diagnosis of epilepsy in general is a clinical one and is typically based on history. Epilepsy is more commonly overdiagnosed than underdiagnosed. An erroneous diagnosis of epilepsy is often the result of weak history and an 'abnormal' EEG. Twenty-five to 30% of patients previously diagnosed with epilepsy who did not respond to initial antiepileptic drug treatment do not have epilepsy. Most patients misdiagnosed with epilepsy turn out to have either psychogenic nonepileptic attacks or syncope. Reasons for reading a normal EEG as an abnormal one include over-reading normal variants or simple fluctuations of background rhythms. Reversing the diagnosis of epilepsy is challenging and requires reviewing the 'abnormal' EEG, which can be difficult. The lack of mandatory training in neurology residency programs is one of the main reasons for normal EEGs being over-read as abnormal. Tests (including EEG) should not be overemphasized over clinical judgment. The diagnosis of epilepsy can be challenging, and some seizure types may be underdiagnosed. Frontal lobe hypermotor seizures may be misdiagnosed as psychogenic events. Focal unaware cognitive seizures in elderly maybe be blamed on dementia, and ictal or interictal psychosis in frontal and temporal lobe epilepsies may be mistaken for a primary psychiatric disorder.

It is presumed that the EEG records only cerebral activity. However, frequently it can include other electrical activities, referred to as noise or artifact, which are not of cerebral origin. In the last few decades, evolution in digital technology has greatly improved the ability to record and display interpretable EEG. With the widespread availability of prolonged EEG recording, new artifacts have been described. The addition of concomitant video with audio during recordings has allowed in most instances to determine the source of certain artifacts. One of the challenges of interpreting EEGs consists of identifying artifacts correctly. Some of the EEG artifacts are so distinctive in appearance that the experienced reader can readily identify them. It is not uncommon for normal EEGs to be overinterpreted, especially by inexperienced readers. Failing to identify artifacts correctly can lead to "over reading" a study and doing so can result in misdiagnosis of epilepsy. This in turn can result in inappropriate treatments that ultimately can have serious clinical implications. This review will provide a description of the most commonly encountered artifacts that mimic spike or sharp waves, also referred to as interictal epileptiform discharges. In addition, we will describe troubleshooting approaches to eliminate these artifacts whenever possible. Artifacts that mimic ictal discharges will be reviewed in a different section.

ObjectiveTo identify brain regions underlying interictal generalized paroxysmal fast activity (GPFA), and their causal interactions, in children and adults with Lennox-Gastaut syndrome (LGS).MethodsConcurrent scalp EEG-fMRI was performed in 2 separately analyzed patient groups with LGS: 10 children (mean age 8.9 years) scanned under isoflurane-remifentanil anesthesia and 15 older patients (mean age 31.7 years) scanned without anesthesia. Whole-brain event-related analysis determined GPFA-related activation in each group. Results were used as priors in a dynamic causal modeling (DCM) analysis comparing evidence for different neuronal hypotheses describing initiation and propagation of GPFA between cortex, thalamus, and brainstem.ResultsA total of 1,045 GPFA events were analyzed (cumulative duration 1,433 seconds). In both pediatric and older groups, activation occurred in distributed association cortical areas, as well as the thalamus and brainstem (p < 0.05, corrected for family-wise error). Activation was similar across individual patients with structural, genetic, and unknown etiologies of epilepsy, particularly in frontoparietal cortex. In both groups, DCM revealed that GPFA was most likely driven by prefrontal cortex, with propagation occurring first to the brainstem and then from brainstem to thalamus.ConclusionsWe show reproducible evidence of a cortically driven process within the epileptic network of LGS. This network is present early (in children) and late (in older patients) in the course of the syndrome and across diverse etiologies of epilepsy, suggesting that LGS reflects shared “secondary network” involvement. A cortical-to-subcortical hierarchy is postulated whereby GPFA rapidly propagates from prefrontal cortex to the brainstem via extrapyramidal corticoreticular pathways, whereas the thalamus is engaged secondarily.

ObjectiveTo facilitate the diagnosis of vestibular disorders by patient-initiated capture of ictal nystagmus.MethodsAdults from an Australian neurology outpatient clinic reporting recurrent vertigo were recruited prospectively and taught to self-record spontaneous and positional nystagmus at home while symptomatic, using miniature video-oculography goggles. Consenting patients with ictal videorecordings and a final unblinded clinical diagnosis of Ménière disease (MD), vestibular migraine (VM), or benign paroxysmal positional vertigo (BPPV) were included.ResultsIctal eye videos of 117 patients were analyzed. Of 43 patients with MD, 40 showed high-velocity spontaneous horizontal nystagmus (median slow-phase velocity [SPV] 39.7°/s; 21 showed horizontal nystagmus reversing direction within 12 hours [24 on separate days]). In 44 of 67 patients with VM, spontaneous horizontal (n = 28, 4.9°/s), upbeating (n = 6, 15.5°/s), or downbeating nystagmus (n = 10, 5.1°/s) was observed; 16 showed positional nystagmus only, and 7 had no nystagmus. Spontaneous horizontal nystagmus with SPV >12.05°/s had a sensitivity and specificity of 95.3% and 82.1% for MD (95% confidence interval [CI] 0.84–0.99, 0.71–0.90). Nystagmus direction change within 12 hours was highly specific (95.7%) for MD (95% CI 0.85–0.99). Spontaneous vertical nystagmus was highly specific (93.0%) for VM (95% CI 0.81–0.99). In the 7 patients with BPPV, spontaneous nystagmus was absent or ConclusionPatient-initiated vestibular event monitoring is feasible and could facilitate rapid and accurate diagnosis of episodic vestibular disorders.

ObjectiveTo investigate the dynamic functional connectivity of thalamocortical networks in interictal migraine patients and whether clinical features are associated with abnormal connectivity.MethodsWe investigated dynamic functional network connectivity (dFNC) of the migraine brain in 89 interictal migraine patients and 70 healthy controls. We focused on the temporal properties of thalamocortical connectivity using sliding window cross-correlation, clustering state analysis, and graph-theory methods. Relationships between clinical symptoms and abnormal dFNC were evaluated using a multivariate linear regression model.ResultsFive dFNC brain states were identified to characterize and compare dynamic functional connectivity patterns. We demonstrated that migraineurs spent more time in a strongly interconnected between-network state, but they spent less time in a sparsely connected state. Interestingly, we found that abnormal posterior thalamus (pulvinar nucleus) dFNC with the visual cortex and the precuneus were significantly correlated with headache frequency of migraine. Further topologic measures revealed that migraineurs had significantly lower efficiency of information transfer in both global and local dFNC.ConclusionOur results demonstrated a transient pathologic state with atypical thalamocortical connectivity in migraineurs and extended current findings regarding abnormal thalamocortical networks and dysrhythmia in migraine.

Purpose EEG is a common diagnostic tool to localize epileptic activity with excellent temporal resolution and, however, with relatively low spatial resolution. High-density EEG recording is limited in clinical practice, mainly because of electrode placement difficulties, need of high technical skills, and advanced equipment requirement. Methods We described the technique of long-term EEG recording using a 128-channel neoprene cap placed with a dielectric paste in 7 patients with refractory epilepsy. We captured electrographic seizures in six of seven patients. The 128-channel EEG cap was well tolerated except for a mild headache. Daily impedance checks and reapplication of the high impedance leads maintained the recording with impedances below 10 kΩ. Results Successful long-term recording of high-density EEG was able to capture seizures in six of seven patients. The time needed to apply the electrodes was approximately 1 hour and approximately 30 minutes daily for maintenance. The EEG source localization was obtained in six of seven patients, concordant within the sublobar region for both standard and high-density EEG recordings. Three patients reported a mild headache not leading to discontinuation of the recording. Conclusions In general, long-term high-density scalp EEG recording with a dielectric paste is well tolerated and allows capturing both interictal and ictal data for localization. This small sample does not show a significant advantage in terms of sublobar localization when high-density EEG source is compared with standard 10 to 20 placement as long as the subtemporal areas are recorded.

Objectives After traumatic brain injury, continuous electroencephalography is widely used to detect electrographic seizures. With the development of standardized continuous electroencephalography terminology, we aimed to describe the prevalence and burden of ictal-interictal patterns, including electrographic seizures after moderate-to-severe traumatic brain injury and to correlate continuous electroencephalography features with functional outcome. Design Post hoc analysis of the prospective, randomized controlled phase 2 multicenter INTREPID study (ClinicalTrials.gov: NCT00805818). Continuous electroencephalography was initiated upon admission to the ICU. The primary outcome was the 3-month Glasgow Outcome Scale-Extended. Consensus electroencephalography reviews were performed by raters certified in standardized continuous electroencephalography terminology blinded to clinical data. Rhythmic, periodic, or ictal patterns were referred to as "ictal-interictal continuum"; severe ictal-interictal continuum was defined as greater than or equal to 1.5 Hz lateralized rhythmic delta activity or generalized periodic discharges and any lateralized periodic discharges or electrographic seizures. Setting Twenty U.S. level I trauma centers. Patients Patients with nonpenetrating traumatic brain injury and postresuscitation Glasgow Coma Scale score of 4-12 were included. Interventions None. Measurements and main results Among 152 patients with continuous electroencephalography (age 34 ± 14 yr; 88% male), 22 (14%) had severe ictal-interictal continuum including electrographic seizures in four (2.6%). Severe ictal-interictal continuum burden correlated with initial prognostic scores, including the International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (r = 0.51; p = 0.01) and Injury Severity Score (r = 0.49; p = 0.01), but not with functional outcome. After controlling clinical covariates, unfavorable outcome was independently associated with absence of posterior dominant rhythm (common odds ratio, 3.38; 95% CI, 1.30-9.09), absence of N2 sleep transients (3.69; 1.69-8.20), predominant delta activity (2.82; 1.32-6.10), and discontinuous background (5.33; 2.28-12.96) within the first 72 hours of monitoring. Conclusions Severe ictal-interictal continuum patterns, including electrographic seizures, were associated with clinical markers of injury severity but not functional outcome in this prospective cohort of patients with moderate-to-severe traumatic brain injury. Importantly, continuous electroencephalography background features were independently associated with functional outcome and improved the area under the curve of existing, validated predictive models.

Background Many patients with neurological insults requiring neurointensive care have an increased risk of acute symptomatic seizures. Various nursing interventions performed when caring for these patients may elicit pathological cerebral electrical activity including seizures and stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs). The aim was to explore changes in electroencephalogram (EEG) due to neurointensive care nursing interventions. Methods A convenience sample was recruited between November 2015 and April 2016, consisting of 12 adult patients with impaired consciousness due to a neurosurgical condition. Continuous EEG and simultaneous video recordings of nursing interventions were collected 48 continuous hours for each patient. Two analysts categorized the video recordings for common nursing interventions, and a neurophysiologist analyzed the EEGs. Results In total, 976 nursing interventions were observed. Epileptiform activity was observed in 4 patients (33%), during 1 nursing intervention episode each (0.4%). The 4 observed episodes of epileptiform activity occurred during multiple simultaneous nursing interventions (n = 3) and hygienic interventions (n = 1). Stimulus-induced rhythmic, periodic, or ictal discharges were observed in 1 patient (8%), in 1 single nursing intervention (0.1%). The observed SIRPIDs occurred during repositioning of the patient. All patients had muscle artifacts, during 353 nursing interventions (36.3%). The duration of nursing interventions was longer for those with simultaneous muscle artifacts (median, 116 seconds) than those without muscle artifacts, epileptiform activity, or SIRPIDs (median, 89.0 seconds). With regard to epileptiform activity and SIRPIDs, the median durations of the nursing interventions were 1158 and 289 seconds, respectively. Conclusion The results of this pilot study indicate that muscle artifacts seem prevalent during nursing interventions and may be a sign of stress. Nurses should be aware of the risk of inducing stress by performing regular nursing interventions in daily practice, consider shorter or fewer interventions at a time in sensitive patients, and administer sedation accordingly. Considering that this was a pilot study, more research that investigates correlations between EEG patterns and nursing interventions in larger samples is needed.

Purpose To design a non-patient-specific system to detect the electrical onset of seizures in patients with temporal lobe epilepsy. Methods We used EEG data from 29 seizures of 18 temporal lobe epilepsy patients who underwent multiday video-scalp EEG monitoring as part of their presurgical evaluations. We segmented each data set into preictal and ictal phases, and identified spectral entropy, spectral energy, and signal energy as useful features for discriminating normal and seizure conditions. The performance of five different classifiers was analyzed using these features to design an automated detection system. Results Among the five classifiers, decision tree, k-nearest neighbor, and support vector machine performed with sensitivity (specificity) of 79% (81%), 75% (85%), and 80% (86%), respectively. The other two, linear discriminant algorithm and Naive Bayes classifiers, performed with sensitivity (specificity) of 54% (94%), 47% (96%), respectively. Conclusions The support vector machine-based seizure detection system showed better detection capability in terms of sensitivity and specificity measures as compared to linear discriminant algorithm, Naive Bayes, decision tree, and k-nearest neighbor classifiers. Conclusions Our study shows that a generalized system to detect the electrical onset of seizures in temporal lobe epilepsy using scalp-recorded EEG is possible. If confirmed on a larger data set, our findings may have significant implications for the management of seizures, especially in patients with drug-resistant epilepsy.

ObjectiveTo analyze the factors that determine the occurrence or severity of postictal hypoxemia in the immediate aftermath of a generalized convulsive seizure (GCS).MethodsWe reviewed the video-EEG recordings of 1,006 patients with drug-resistant focal epilepsy included in the REPO2MSE study to identify those with ≥1 GCS and pulse oximetry (SpO2) measurement. Factors determining recovery of SpO2 ≥ 90% were investigated using Cox proportional hazards models. Association between SpO2 nadir and person- or seizure-specific variables was analyzed after correction for individual effects and the varying number of seizures.ResultsA total of 107 GCS in 73 patients were analyzed. A transient hypoxemia was observed in 92 GCS (86%). Rate of GCS with SpO2 p = 0.046). Early recovery of SpO2 ≥90% was associated with early administration of oxygen (p = 0.004), absence of postictal generalized EEG suppression (PGES) (p = 0.014), and extratemporal lobe epilepsy (p = 0.001). Lack of early administration of O2 (p = 0.003), occurrence of PGES (p = 0.018), and occurrence of ictal hypoxemia during the focal phase (p = 0.022) were associated with lower SpO2 nadir.ConclusionPostictal hypoxemia was observed in the immediate aftermath of nearly all GCS but administration of oxygen had a strong preventive effect. Severity of postictal hypoxemia was greater in temporal lobe epilepsy and when hypoxemia was already observed before the onset of secondary GCS.

A 17-year-old elite triathlete presented with recurrent loss of consciousness events. Implantable loop recorder (ILR) documented sinus node asystoles of up to 21 seconds. She underwent cardiac neuromodulation ablation. After ablation, a generalized tonic-clonic seizure (GTCS) occurred, without concomitant asystole on the ILR. Temporal lobe seizures were diagnosed and supported by interictal epileptic activity on electroencephalogram. We assumed that the syncope episodes were ictal asystole (IA) and that the IA terminated the epileptic seizures early after their onset. The cardiac ablation prevented IA, enabling spread of seizure activity and development of GTCS. To the best of our knowledge, this is the first case of IA treated with cardiac ablation, allowing avoidance of cardiac pacing. This case raises the awareness to epileptic seizures as a cause of asystole in athletes, with an elusive and atypical presentation.

Migraine-type photophobia, most commonly described as exacerbation of headache by light, affects nearly 90% of the patients. It is classified as one of the most disabling symptoms that accompany an attack. Using subjective psychophysical assessments, we showed recently that migraine patients are more sensitive to all colors of light during the ictal than during the interictal phase and that control subjects do not experience pain when exposed to different colors of light. Based on these findings, we suggested that color preference is unique to migraineurs (as it was not found in control subjects) rather than migraine phase (as it was found in the ictal and interictal phases). To identify the origin of this photophobia in migraineurs, we compared the electrical waveforms that were generated in the retina and visual cortex of 46 interictal migraineurs to those generated in 42 healthy controls using color-based electroretinography and visual evoked potential paradigms. Unexpectedly, it was the amplitude of the retinal rod-driven b-wave, which was consistently larger (by 14-19% in the light-adapted and 18-34% in the dark-adapted flash ERG) in the migraineurs than in the controls, rather than the retinal cone-driven a-wave or the visual evoked potentials that differ most strikingly between the two groups. Mechanistically, these findings suggest that the inherent hypersensitivity to light among migraine patients may originate in the retinal rods rather than retinal cones or the visual cortex. Clinically, the findings may explain why migraineurs complain that the light is too bright even when it is dim to the extent that non-migraineurs feel as if they live in a cave.

ObjectiveTo study the diagnostic value of volume perfusion CT (VPCT) in patients with transient focal neurologic deficits following and during epileptic seizures, that mimic symptoms of stroke.MethodsA retrospective case-control study was performed on 159 patients who presented with a seizure and received an emergency VPCT within the first 3.5 hours of admission, after being misjudged to have an acute stroke. The reference test was a clinical-based, EEG-supported diagnostic algorithm for seizure.ResultsWe included 133 patients: 94 stroke-mimicking cases with postictal focal neurologic deficits (“Todd phenomenon,” n = 67) or ongoing seizure on hospital admission (“ictal patients,” n = 27), and 39 postictal controls without focal neurologic deficits. Patients with Todd phenomenon showed normal perfusion (64%), hypoperfusion (21%), and hyperperfusion (14%) on early VPCT. Ictal patients displayed more hyperperfusion compared to postictal patients (p = 0.015). Test sensitivity of hyperperfusion for ictal patients is 38% (95% confidence interval [CI] 20.7%–57.7%), specificity 86% (95% CI 77.3%–91.7%), positive predictive value is 42% (95% CI 27.5%–58.7%), and the negative predictive value 83% (95% CI 78.6%–86.9%). A cortical distribution was seen in all hyperperfusion scans, compared to a cortico-subcortical pattern in hypoperfusion (p < 0.001). A history of complex focal seizure and age were associated with hyperperfusion (p = 0.046 and 0.038, respectively).ConclusionVPCT can differentiate ictal stroke mimics with hyperperfusion from acute ischemic stroke, but not postictal patients who display perfusion patterns overlapping with ischemic stroke.Classification of evidenceThis study provides Class IV evidence that VPCT accurately differentiates ictal stroke mimics from acute ischemic stroke.

Purpose It has been challenging to detect early changes preceding seizure onset in patients with epilepsy. This study investigated the preictal discharges (PIDs) by intracranial electroencephalogram of 11 seizures from 7 patients with mesial temporal lobe epilepsy. Methods The EEG segments consisting of 30 seconds before ictal onset and 5 seconds after ictal onset were selected for analysis. After PID detection, the amplitude and interval were measured. According to the timing of PID onset, the 30-second period preceding seizure onset was divided into two stages: before PID stage and PID stage. The autocorrelation coefficients during the two stages were calculated and compared. Results Preictal discharge amplitude progressively increased, while PID interval gradually decreased toward seizure onset. The autocorrelation coefficients of PID channels were significantly higher during PID stage than before PID stage. There was an overlap between channels with PIDs and seizure onset channels (80.77%). Conclusions Preictal discharges emerge prior to ictal event, with a dynamic change and a spatial correlation with seizure onset zone. These findings deepen our understanding of seizure generation and help early prediction and localization of seizure onset zone.

Studies in interictal migraine show either normal or impaired pain modulation, at the psychophysical level. To date, pain modulation in migraineurs has yet to be explored concurrent with imaging methods. We aimed to investigate brain activity associated with endogenous analgesia by functional magnetic resonance imaging in attack-free migraineurs. Thirty-nine episodic migraineurs and 35 controls participated. Endogenous analgesia efficiency was assessed by the conditioned pain modulation (CPM) paradigm during functional magnetic resonance imaging. Conditioned pain modulation included 4 stimulation sequences of either test stimulus (noxious contact heat at forearm) given stand alone (Ts_alone) or concomitant to contralateral foot immersion in cold water (Ts_conditioned). The psychophysical CPM (Ts_conditioned minus Ts_alone; 0-10 numerical rating scale) and related brain activity were examined. No group differences were found in the psychophysical CPM (controls: -0.52 ± 0.80; migraineurs: -0.20 ± 0.88; repeated-measures analysis of variance: P = 0.110) or related brain activity (family wise error [P < 0.05] correction at the voxel level). Within groups, controls showed a significant CPM effect (Ts_alone: 6.15 ± 2.03 vs Ts_conditioned: 5.63 ± 1.97; P < 0.001), whereas migraineurs did not (Ts_alone: 5.60 ± 1.92 vs Ts_conditioned: 5.39 ± 2.30; P = 0.153); yet, both groups showed significant CPM-related decreased deactivation in prefrontal areas including the superior frontal gyrus and parietal regions including precuneus. The change in brain activity seems related to task demands rather than to pain reduction. The lack of group difference between migraineurs and controls in CPM and its related brain activity may result from (1) the specific CPM methodology used in this study, since migraineurs are reported to show various pain modulation efficiency for different test paradigms and/or (2) pathophysiological diversity of patients with migraine.

ObjectiveTo examine whether interictal plasma pituitary adenylate cyclase-activating peptide 38-like immunoreactivity (PACAP38-LI) shows correlation with the microstructural integrity of the white matter in migraine.MethodsInterictal plasma PACAP38-LI was measured by radioimmunoassay in 26 patients with migraine (24 women) who underwent diffusion tensor imaging afterward using a 1.5-tesla magnetic resonance scanner. Data were analyzed using tract-based spatial statistics included in FMRIB's Software Library.ResultsInterictal plasma PACAP38-LI showed significant correlation with mean diffusivity (p < 0.0179) mostly in the bilateral occipital white matter spreading into parietal and temporal white matter. Axial and radial diffusivity showed positive correlation with interictal PACAP38-LI (p < 0.0432 and p < 0.0418, respectively) in the left optic radiation and left posterior corpus callosum. Fractional anisotropy did not correlate significantly with PACAP38-LI. With disease duration as a nuisance regressor in the model, PACAP38-LI correlated with axial and mean diffusivity in the left thalamus (p < 0.01).ConclusionWe report a link between PACAP38, a pathobiologically important neurochemical biomarker, and imaging markers of the disease that may bolster further research into the role of PACAP38 in migraine.

ObjectiveTo evaluate the use of interictal high-frequency oscillations (HFOs) in epilepsy surgery for prediction of postsurgical seizure outcome in a prospective multicenter trial.MethodsWe hypothesized that a seizure-free outcome could be expected in patients in whom the surgical planning included the majority of HFO-generating brain tissue while a poor seizure outcome could be expected in patients in whom only a few such areas were planned to be resected. Fifty-two patients were included from 3 tertiary epilepsy centers during a 1-year period. Ripples (80–250 Hz) and fast ripples (250–500 Hz) were automatically detected during slow-wave sleep with chronic intracranial EEG in 2 centers and acute intraoperative electrocorticography in 1 patient.ResultsThere was a correlation between the removal of HFO-generating regions and seizure-free outcome at the group level for all patients. No correlation was found, however, for the center-specific analysis, and an individual prognostication of seizure outcome was true in only 36 patients (67%). Moreover, some patients became seizure-free without removal of the majority of HFO-generating tissue. The investigation of influencing factors, including comparisons of visual and automatic analysis, using a threshold analysis for areas with high HFO activity, and excluding contacts bordering the resection, did not result in improved prognostication.ConclusionsOn an individual patient level, a prediction of outcome was not possible in all patients. This may be due to the analysis techniques used. Alternatively, HFOs may be less specific for epileptic tissue than earlier studies have indicated.

We propose a comprehensive review of the subject of epileptiform and potentially harmful EEG patterns that lie on the interictal continuum (IIC) to help with therapeutic decision-making and target future research. This approach to "electro-physiological SE" encompasses five dimensions of the IIC: it characterizes a periodic or rhythmic pattern, not only regarding its ictal morphology and potential harm with secondary neuronal injury, but also addresses the "metabolic footprint," clinical repercussion, and epileptogenic potential. Recent studies have attempted to determine and qualify the ictal nature and the epileptogenic potential (i.e., risk of subsequent acute seizures) of particular IIC patterns and their intrinsic EEG characteristics. Others have correlated non-convulsive seizures with cognitive outcomes beyond mortality; non-convulsive seizures and sporadic, periodic, or rhythmic discharges to encephalopathy severity; and the spectrum of periodic or rhythmic patterns to measurable secondary brain injury. Equivocal periodic or rhythmic patterns on the IIC are frequently encountered in critical care neurology where clinicians often incorporate advanced neuroimaging, metabolic neuromonitoring, and anti-seizure drug short trials, in an effort to gauge these patterns. We propose portraying the IIC with a multiaxial graph to disambiguate each of these risks. Quantification along each axis may help calibrate therapeutic urgency. An adaptable scoring system assesses which quasi-ictal EEG patterns in this spectrum might reach the tipping point toward anti-seizure drug escalation, in neurocritically ill patients.

Objective Evidence suggests that magnetic seizure therapy (MST) results in fewer side effects than electroconvulsive treatment, both in humans treated with electroconvulsive therapy (ECT) as well as in the animal preclinical model that uses electroconvulsive shock (ECS). Evidence suggests that MST results in fewer cognitive side effects than ECT. Although MST offers enhanced control over seizure induction and spread, little is known about how MST and ECT seizures differ. Seizure characteristics are associated with treatment effect. This study presents quantitative analyses of electroencephalogram (EEG) power after electrical and magnetic seizure induction and anesthesia-alone sham in an animal model. The aim was to test whether differential neurophysiological characteristics of the seizures could be identified that support earlier observations that the powers of theta, alpha, and beta but not delta frequency bands were lower after MST when compared with those after ECS. Methods In a randomized, sham-controlled trial, 24 macaca mulatte received 6 weeks of daily sessions while scalp EEG was recorded. Electroencephalogram power was quantified within delta, theta, alpha, and beta frequency bands. Results Magnetic seizure therapy induced lower ictal expression in the theta, alpha and beta frequencies than ECS, but MST and ECS were indistinguishable in the delta band. Magnetic seizure therapy showed less postictal suppression than ECS. Increasing electrical dosage increased ictal power, whereas increasing MST dosage had no effect on EEG expression. Conclusions Magnetic seizure therapy seizures have less robust electrophysiological expression than ECS, and these differences are largest in the alpha and beta bands. The relevance of these differences in higher frequency bands to clinical outcomes deserves further exploration. Significance Contrasting EEG in ECS and MST may lead to insights on the physiological underpinnings of seizure-induced amnesia and to finding ways to reduce cognitive side effects.

PURPOSE Periodic discharges (PDs) are EEG patterns denoting brain dysfunction and ictal tendency. Their exact meaning regarding etiology and outcomes is not well known. In particular, bilateral independent PDs (BIPDs) are poorly described. METHODS We performed a retrospective, multicenter study evaluating neuroimaging, epileptic, clinical, and EEG correlates of BIPDs. RESULTS Twenty-five patients studied with a mean Glasgow Coma Scale 6.5 and modified Rankin scale 3.9 who underwent EEG monitoring, mean duration 287 hours (range 0.75-3,216). Most common causes of BIPDs were cardiac arrest, Central Nervous System infections, and acute/chronic ischemic/hemorrhagic stroke. Most had subcortical and cortical injuries on neuroimaging. Most of the PDs ranged from 0.5 to 2 Hz in frequency, were of multiple phase types, and localized to the frontal head regions. Eighteen of 25 patients had clinical or electrographic seizures. There was a trend toward seizures in those with BIPDs with a history of epilepsy (P = 0.08) and acute metabolic dysfunction (P = 0.08), particularly with coincident acute structural lesions (P = 0.05). Seizures were predicted by bilaterally symmetric frequencies (P = 0.02) and trended toward higher likelihood with PD frequency

Bipolar I disorder and interictal personality syndrome have many overlapping characteristics that are difficult to distinguish. There is scant literature focused on interictal personality syndrome and no case reports to date detailing patients with comorbid bipolar pathology. We describe an individual with a history of bipolar I disorder who developed right temporal lobe epilepsy after several head injuries. He subsequently exhibited symptoms consistent with interictal personality syndrome that were independent of his bipolar symptomatology. Better understanding of these disorders can lead to improved diagnosis and symptom management. The similarities may also point to a partially shared neuropathology.

Purpose We aimed to determine whether conventional standardized EEG features could be consolidated into a more limited number of factors and whether the derived factor scores changed during the acute period after pediatric cardiac arrest. Methods Children resuscitated after cardiac arrest underwent conventional continuous EEG monitoring. The EEG was scored in 12-hour epochs for up to 72-hours after return of circulation by an electroencephalographer using standardized critical care EEG terminology. We performed a polychoric factor analysis to determine whether numerous observed EEG features could be represented by a smaller number of derived factors. Linear mixed-effects regression models and heat maps evaluated whether the factor scores remained stable across epochs. Results We performed EEG monitoring in 89 consecutive children, which yielded 453 EEG segments. We identified two factors, which were not correlated. The background features were factor loaded with the features continuity, voltage, and frequency. The intermittent features were factor loaded with the features of seizures, periodic patterns, and interictal discharges. Factor scores were calculated for each EEG segment. Linear, mixed-effect, regression results indicated that the factor scores did not change over time for the background features factor (coefficient, 0.18; 95% confidence interval, 0.04-0.07; P = 0.52) or the intermittent features factor (coefficient, -0.003; 95% confidence interval, -0.02 to 0.01; P = 0.70). However, heat maps showed that some individual subjects did experience factor score changes over time, particularly if they had medium initial factor scores. Conclusions Subsequent studies assessing whether EEG is informative for neurobehavioral outcomes after pediatric cardiac arrest could combine numerous EEG features into two factors, each reflecting multiple background and intermittent features. Furthermore, the factor scores would be expected to remain stable during the acute period for most subjects.

Background Radiofrequency thermocoagulation of epileptogenic foci via stereoelectroencephalography (SEEG) electrodes has been suggested as a treatment for medically intractable epilepsy, but reported outcomes have been suboptimal, possibly because lesions generated using conventional high-energy radiofrequency parameters are relatively small. Objective To describe a technique of delivering low energy across separate SEEG electrodes in order to create large confluent radiofrequency lesions. Methods The size and configuration of radiofrequency lesions using different radiofrequency intensity and interelectrode distance was assessed in egg whites. Magnetic resonance images (MRI) from 3 patients who had undergone radiofrequency lesion creation were evaluated to determine the contribution of lesion intensity and electrode separation on lesion size. Electroencephalography, MRI, and clinical data were assessed before and after lesion creation. Results Both in Vitro and in Vivo analysis revealed that less energy paradoxically produced larger lesions, with the largest possible lesions produced when radiofrequency power was applied for long duration at less than 3 W. Linear separation of electrodes also contributed to lesion size, with largest lesions produced when electrodes were separated by a linear distance of between 5 and 12 mm. Clinical lesions produced using these parameters were large and resulted in improvement in interictal and ictal activity. Conclusion Radiofrequency lesions produced using low-energy delivery between SEEG electrodes in close proximity can produce a large lesion. These findings might have advantages for treatment of focal epilepsy.

Purpose The long-term electrographic features of lateralized periodic discharges (LPD) and their impact on clinical management are unclear. The authors investigated routine EEGs (rEEG) to analyze the delayed natural history of LPDs, and studied the clinical care of these patients. Methods After IRB approval, the prospectively maintained continuous EEG (cEEG) database was searched to identify patients fulfilling the following criteria: LPDs on cEEG, age ≥18 years, no epilepsy history, and rEEG completed within 1 to 12 months of hospital discharge. Their rEEGs were reviewed followed by clinical data extraction. Appropriate statistical tools were used for data analysis. Results Thirty-nine patients (20 females) with a mean age of 63.3 ± 16.8 years at the time of cEEG fulfilled the study criteria. Thirty-three (85%) had associated electrographic seizures. rEEG was performed 4.7 ± 3.5 months after cEEG. Seven (18%) patients had interictal epileptiform discharges (IEDs) on the rEEG. The LPDs on cEEG of these patients were more often continuous, with an amplitude >2 times their background compared with 10 (26%) patients with normal rEEGs findings. After a mean follow-up of 19.8 ± 9.9 months, 11 (31%) patients developed epilepsy, but only 3 had IEDs on their rEEG. Majority (86%) of patients were on AEDs at the time of last follow-up. Conclusions LPDs lead to markers of epileptogenicity in around 18% of patients. One-third of the study population developed epilepsy. rEEG findings were not found to be good indicators of epilepsy development in our small, retrospective study limited by its sampling bias. Indiscriminate, long-term use of AEDs in these patients is a concerning finding.