Electrographic Seizures Research Articles

Can we improve electrocorticography using a circular grid array in brain tumor surgery?

Intraoperative electrocorticography (iECoG) is used as an adjunct to localize the epileptogenic zone during surgical resection of brain tumors in patients with focal epilepsies. It also enables monitoring of after-discharges and seizures with EEG during functional brain mapping with electrical stimulation. When seizures or after-discharges are present, they complicate accurate interpretation of the mapping strategy to outline the brain’s eloquent function and can affect the surgical procedure. Recurrent seizures during surgery requires urgent treatment and, when occurring during awake craniotomy, often leads to premature termination of brain mapping due to post-ictal confusion or sedation from acute rescue therapy. There are mixed results in studies on efficacy with iECoG in patients with epilepsy and brain tumors influencing survival and functional outcomes following surgery. Commercially available electrode arrays have inherent limitations. These could be improved with customization potentially leading to greater precision in safe and maximal resection of brain tumors. Few studies have assessed customized electrode grid designs as an alternative to commercially available products. Higher density electrode grids with intercontact distances less than 1 cm improve spatial delineation of electrophysiologic sources, including epileptiform activity, electrographic seizures, and afterdischarges on iECoG during functional brain mapping. In response to the shortcomings of current iECoG grid technologies, we designed and developed a novel higher-density hollow circular electrode grid array. The 360-degree iECoG monitoring capability allows continuous EEG recording during surgical intervention through the aperture with and without electrical stimulation mapping. Compared with linear strip electrodes that are commonly used for iECoG during surgery, the circular grid demonstrates significant benefits in brain tumor surgery. This includes quicker recovery of post-operative motor deficits (2.4 days versus 9 days, p = 0.05), more extensive tumor resection (92.0% versus 77.6%, p = 0.003), lesser reduction in Karnofsky Performance scale postoperatively (−2 versus −11.6, p = 0.007), and more sensitivity to recording afterdischarges. In this narrative review, we discuss the advantages and disadvantages of commercially available recording devices in the operating room and focus on the usefulness of the higher-density circular grid.

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

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

Long-Term Intracranial EEG Lateralization of Epileptogenicity in Patients With Confirmed or Suspected Bilateral Mesial Temporal Lobe Onsets During Epilepsy Surgical Evaluation.

The data resulting from epilepsy surgical evaluation are occasionally unclear in cases of mesial temporal lobe (MTL) epilepsy. Long-term intracranial EEG (iEEG) collected by the Responsive Neurostimulation (RNS) System may be an approach for capturing additional seizure data while treating patients with neurostimulation. We reviewed iEEG seizure lateralization and clinical outcomes in bilateral MTL patients at University of Utah. Long-term RNS System iEEG seizure lateralization was compared with pre-RNS System lateralization obtained during surgical evaluation. Safety and clinical outcomes were extracted retrospectively from patient records. Twenty-six patients received an RNS System with bilateral MTL leads. Fifteen of the patients had adequate follow-up to report clinical outcomes ( > 1 year), and 25 patients had enough recorded data ( > 6 months) to perform iEEG analysis. Median percent reduction in clinical seizures at last follow-up was 58%, and 40% reported being seizure-free at last follow-up, for variable durations. The electrographic seizure lateralization (unilateral vs. bilateral) differed between surgical evaluation and long-term iEEG in 44% of our patients. In the subset of eight patients (32%) who had only unilateral seizures recorded during surgical evaluation, but were implanted with bilateral MTL leads based on bilateral interictal epileptiform discharges, 62% (5/8) had bilateral seizures recorded on long-term iEEG. Interestingly, in the 18 patients who had bilateral seizures recorded during surgical evaluation, 28% (5/18) were found to be unilateral on long-term iEEG. Our data suggest that RNS System implantation in suspected bilateral MTL cases may be an option to assess a patient's true seizure lateralization on long-term iEEG. Responsive neuromodulation should be considered before resection or ablation in cases that have evaluation data suggesting bilaterality.

Lack of spontaneous typical seizures during intracranial monitoring with stereo-electroencephalography.

In the presurgical evaluation of patients with drug-resistant epilepsy (DRE), occasionally, patients do not experience spontaneous typical seizures (STS) during a stereo-electroencephalography (SEEG) study, which limits its effectiveness. We sought to identify risk factors for patients who did not have STS during SEEG and to analyze the clinical outcomes for this particular set of patients. We conducted a retrospective analysis of all patients with DRE who underwent depth electrode implantation and SEEG recordings between January 2013 and December 2018. SEEG was performed in 155 cases during this period. Eleven (7.2%) did not experience any clinical seizures (non-STS group), while 143 experienced at least one patient-typical seizure during admission (STS group). No significant differences were found between STS and non-STS groups in terms of patient demographics, lesional/non-lesional epilepsy ratio, pre-SEEG seizure frequency, number of ASMs used, electrographic seizures or postoperative seizure outcome in those who underwent resective surgery. Statistically significant differences were found in the average number of electrodes implanted (7.0 in the non-STS group vs. 10.2 in STS), days in Epilepsy Monitoring Unit (21.8 vs. 12.8 days) and the number of cases that underwent resective surgery following SEEG (27.3% vs 60.8%), respectively. The three non-STS patients (30%) who underwent surgery, all had their typical seizures triggered during ECS studies. Three cases were found to have psychogenic non-epileptic seizures. None of the patients in the non-STS group were offered neurostimulation devices. Five of the non-STS patients experienced transient seizure improvement following SEEG. We were unable to identify any factors that predicted lack of seizures during SEEG recordings. Resective surgery was only offered in cases where ECS studies replicated patient-typical seizures. Larger data sets are required to be able to identify factors that predict which patients will fail to develop seizures during SEEG.

Assessing 72 h vs. 24 h of long-term video-EEG monitoring to confirm the diagnosis of epilepsy: a retrospective observational study.

Paroxysmal seizure-like events can be a diagnostic challenge. Inpatient video-electroencephalography (EEG) monitoring (VEM) can be a valuable diagnostic tool, but recommendations for the minimal duration of VEM to confirm or rule out epilepsy are inconsistent. In this study, we aim to determine whether VEM of 48 or 72 h was superior to 24 h. In this monocentric, retrospective study, we included 111 patients with paroxysmal, seizure-like events who underwent at least 72 h of VEM. Inclusion criteria were as follows: (1) Preliminary workup was inconclusive; (2) VEM admission occurred to confirm a diagnosis; (3) At discharge, the diagnosis of epilepsy was conclusively established. We analyzed the VEM recordings to determine the exact time point of the first occurrence of epileptic abnormalities (EAs; defined as interictal epileptiform discharges or electrographic seizures). Subgroup analyses were performed for epilepsy types and treatment status. In our study population, 69.4% (77/111) of patients displayed EAs during VEM. In this group, the first occurrence of EAs was observed within 24 h in 92.2% (71/77) of patients and within 24-72 h in 7.8% (6/77). There was no statistically significant difference in the incidence of EA between medicated and non-medicated patients or between focal, generalized epilepsies and epilepsies of unknown type. Of the 19 recorded spontaneous electroclinical seizures, 6 (31.6%) occurred after 24 h. A VEM of 24 h may be sufficient in the diagnostic workup of paroxysmal seizure-like events under most circumstances. Considering the few cases of first EA in the timeframe between 24 and 72 h, a prolonged VEM may be useful in cases with a high probability of epilepsy or where other strategies like sleep-EEG or ambulatory EEG show inconclusive results. Prolonged VEM increases the chance of recording spontaneous seizures. Our study also highlights a high share of subjects with epilepsy that do not exhibit EAs during 72 h of VEM.

Treatment of electrographic seizures versus clinical seizures in neonates: A systematic review and meta-analysis

IntroductionElectrographic seizures in neonates are commonly associated with poor neurodevelopmental outcomes. However, there is conflict in evidence whether control of electrographic seizures translate into improved neurodevelopmental outcome. We aimed to evaluate whether treating all electrographic seizures compared with treating clinical seizures leads to a better neurodevelopmental outcome at 18–24 months in neonates. MethodsWe searched four electronic databases (Medline, Cochrane Library, Embase, and Web of Science) for randomized controlled trials (RCTs) published until October 31, 2022. We included RCTs comparing the treatment of electrographic seizures with clinical seizures in neonates with or at risk of seizures. The Risk of Bias version 2 tool was used to assess the risk of bias. The random-effects meta-analysis was performed using RevMan 5.4 software. ResultsOf the 2872 unique records identified by the database search, five trials involving 474 infants were eligible for the review. There was no significant difference in the incidence of neurodevelopmental disability at 18–24 months. Infants in the electrographic seizure group had lower scores in the cognitive domain (2 trials, 186 participants, MD: −5.4; 95% CI:−10.3 to −0.4, I2-0%). There were no significant differences in scores in the motor and language domains, mortality, seizure burden, brain injury scores, antiseizure medication use, and post-neonatal epilepsy. ConclusionsHaving limitations of small number of trials and heterogeneity, the systematic review does not identify evidence demonstrating improved neurodevelopmental outcomes or improved survival in neonates treated for electrographic seizures versus clinical seizures.

Antisense oligonucleotides restore excitability, GABA signalling and sodium current density in a Dravet syndrome model.

Dravet syndrome is an intractable developmental and epileptic encephalopathy caused by de novo variants in SCN1A resulting in haploinsufficiency of the voltage-gated sodium channel Nav1.1. We showed previously that administration of the antisense oligonucleotide STK-001, also called ASO-22, generated using targeted augmentation of nuclear gene output technology to prevent inclusion of the nonsense-mediated decay, or poison, exon 20N in human SCN1A, increased productive Scn1a transcript and Nav1.1 expression and reduced the incidence of electrographic seizures and sudden unexpected death in epilepsy in a mouse model of Dravet syndrome. Here, we investigated the mechanism of action of ASO-84, a surrogate for ASO-22 that also targets splicing of SCN1A exon 20N, in Scn1a+/- Dravet syndrome mouse brain. Scn1a +/- Dravet syndrome and wild-type mice received a single intracerebroventricular injection of antisense oligonucleotide or vehicle at postnatal Day 2. We examined the electrophysiological properties of cortical pyramidal neurons and parvalbumin-positive fast-spiking interneurons in brain slices at postnatal Days 21-25 and measured sodium currents in parvalbumin-positive interneurons acutely dissociated from postnatal Day 21-25 brain slices. We show that, in untreated Dravet syndrome mice, intrinsic cortical pyramidal neuron excitability was unchanged while cortical parvalbumin-positive interneurons showed biphasic excitability with initial hyperexcitability followed by hypoexcitability and depolarization block. Dravet syndrome parvalbumin-positive interneuron sodium current density was decreased compared to wild-type. GABAergic signalling to cortical pyramidal neurons was reduced in Dravet syndrome mice, suggesting decreased GABA release from interneurons. ASO-84 treatment restored action potential firing, sodium current density and GABAergic signalling in Dravet syndrome parvalbumin-positive interneurons. Our work suggests that interneuron excitability is selectively affected by ASO-84. This new work provides critical insights into the mechanism of action of this antisense oligonucleotide and supports the potential of antisense oligonucleotide-mediated upregulation of Nav1.1 as a successful strategy to treat Dravet syndrome.

Ketamine to Prevent Endotracheal Intubation in Adults with Refractory Non-convulsive Status Epilepticus: A Case Series.

Non-convulsive status epilepticus (NCSE) is defined as status epilepticus (SE) with no obvious motor phenomenon and is diagnosed based on electroencephalogram (EEG). Refractory SE (RSE) is the persistence of seizures despite treatment with an adequately dosed first-line and second-line agents. Although guidelines for convulsive RSE include third-line agents such as intravenous anesthetic drugs (midazolam, propofol, or barbiturates), the therapeutic approach to NCSE is not well outlined. Treatment with traditional anesthetics invariably includes endotracheal intubation, which is associated with significant adverse events. Comparatively, ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist is not associated with significant cardiorespiratory depression and may help in avoiding intubation. In this case series, we describe our experience with the early use of intravenous ketamine as the first anesthetic agent in patients with refractory NCSE to avoid endotracheal intubation. We present a case series of nine patients managed in the Neurointensive Care Unit at a university-affiliated tertiary care hospital. The study was approved by the hospital and university institutional review boards and the requirement for informed consent was waived for retrospective analysis of existing data, per institutional policy. All cases of SE were identified from a prospective database, and a subsequent retrospective chart review identified all patients with a diagnosis of refractory NCSE in whom ketamine was used as the first anesthetic agent. The primary endpoint was the avoidance of endotracheal intubation while on ketamine infusion. The secondary endpoint was defined as cessation of both clinical and electrographic seizures recorded on continuous EEG within 24h of ketamine administration. A total of nine patients experiencing refractory NCSE were included in this case series, with a median age of 61 (range 26-72) years and seven patients were male. The primary endpoint, avoiding intubation, was achieved in five out of nine (55%)cases. Six patients experienced resolution of refractory NCSE with ketamine administration as the sole anesthetic agent. Four patients required endotracheal intubation and three patients had a failure of seizure cessation with ketamine. Hypersalivation and pneumonia were the most common ketamine associated adverse events. In non-intubated patients, no deaths occurred. One patient was discharged home, four to subacute rehabilitation, one to along term acute care hospital, and one patient to hospice. The use of ketamine as the primary anesthetic agent may be a reasonable option to avoid endotracheal intubation in a subset of patients with refractory NCSE. This study is limited by its small sample size, retrospective design, and reliance on information obtained from chartreview.

Epileptic manifestations of autoimmune encephalitis

The development of autoimmune encephalitis (AIE) is due to the formation of intracellular and extracellular neuronal antibodies to various structures of the brain tissue. Their prevalence and morbidity are comparable to infectious ones, and the detection rate has recently been increasing. Acute symptomatic seizures are an important component of the clinical core of AIE and are associated with a heterogeneous group of autoantibodies, which along with the features of the lesion topic causes a signi fi cant clinical variety of seizures. The EEG has ictal and interictal features, and the development of electrographic subclinical seizures is also possible. The basis of the treatment of AIE with epileptic seizures is immunotherapy along with the use of antiepileptic drugs with sodium channel blocking properties.

Sex Differences in Organophosphate Model of Benzodiazepine-Refractory Status Epilepticus and Neuronal Damage.

Sex differences are common in human epilepsy. Although men are more susceptible to seizure than women, the mechanisms underlying sex-specific vulnerabilities to seizure are unclear. The organophosphate (OP) diisopropylfluorophosphate (DFP) is known to cause neurotoxicity and status epilepticus (SE), a serious neurologic condition that causes prolonged seizures and brain damage. Current therapies for OP poisoning and SE do not consider neuronal variations between male and female brains. Therefore, we investigated sex-dependent differences in electrographic seizure activity and neuronal injury using the DFP model of refractory SE in rats. Electroencephalogram recordings were used to monitor DFP-induced SE, and the extent of brain injury was determined using fluoro-jade-B staining to detect cellular necrosis. After DFP exposure, we observed striking sex-dependent differences in SE and seizure activity patterns as well as protective responses to midazolam treatment. Following acute DFP exposure, male animals displayed more severe SE with intense epileptiform spiking and greater mortality than females. In contrast, we observed significantly more injured cells and cellular necrosis in the hippocampus and other brain regions in females than in males. We also observed extensive neuronal injury in the somatosensory cortex of males. The anticonvulsant effect of midazolam against SE was limited in this model and found to be similar in males and females. However, unlike males, females exhibited substantially more protection against neuronal damage after midazolam treatment. Overall, these results demonstrate significant sex-dependent differences in DFP-induced refractory SE and neuronal damage patterns, suggesting that it may be possible to develop sex-specific neuroprotective strategies for OP intoxication and refractory SE. SIGNIFICANCE STATEMENT: Sex-dependent differences in neurotoxicity and status epilepticus (SE) are key biological variables after organophosphate (OP) exposure. Here, we investigated sex-dependent differences in SE and brain injury after acute diisopropylfluorophosphate exposure. Male rats had more severe SE and less survival than females, while females had more neuronal damage. Females had more neuroprotection to midazolam than males, while both sexes had similar but partial anticonvulsant effects. These findings suggest that a sex-specific therapeutic approach may prevent neurological complications of OP-induced SE.

Increasing glutathione levels by a novel posttranslational mechanism inhibits neuronal hyperexcitability

Glutathione (GSH) depletion, and impaired redox homeostasis have been observed in experimental animal models and patients with epilepsy. Pleiotropic strategies that elevate GSH levels via transcriptional regulation have been shown to significantly decrease oxidative stress and seizure frequency, increase seizure threshold, and rescue certain cognitive deficits. Whether elevation of GSH per se alters neuronal hyperexcitability remains unanswered. We previously showed that thiols such as dimercaprol (DMP) elevate GSH via post-translational activation of glutamate cysteine ligase (GCL), the rate limiting GSH biosynthetic enzyme. Here, we asked if elevation of cellular GSH by DMP altered neuronal hyperexcitability in-vitro and in-vivo. Treatment of primary neuronal-glial cerebrocortical cultures with DMP elevated GSH and inhibited a voltage-gated potassium channel blocker (4-aminopyridine, 4AP) induced neuronal hyperexcitability. DMP increased GSH in wildtype (WT) zebrafish larvae and significantly attenuated convulsant pentylenetetrazol (PTZ)-induced acute ‘seizure-like’ swim behavior. DMP treatment increased GSH and inhibited convulsive, spontaneous ‘seizure-like’ swim behavior in the Dravet Syndrome (DS) zebrafish larvae (scn1Lab). Furthermore, DMP treatment significantly decreased spontaneous electrographic seizures and associated seizure parameters in scn1Lab zebrafish larvae. We investigated the role of the redox-sensitive mammalian target of rapamycin (mTOR) pathway due to the presence of several cysteine-rich proteins and their involvement in regulating neuronal excitability. Treatment of primary neuronal-glial cerebrocortical cultures with 4AP or l-buthionine-(S,R)-sulfoximine (BSO), an irreversible inhibitor of GSH biosynthesis, significantly increased mTOR complex I (mTORC1) activity which was rescued by pre-treatment with DMP. Furthermore, BSO-mediated GSH depletion oxidatively modified the tuberous sclerosis protein complex (TSC) consisting of hamartin (TSC1), tuberin (TSC2), and TBC1 domain family member 7 (TBC1D7) which are critical negative regulators of mTORC1. In summary, our results suggest that DMP-mediated GSH elevation by a novel post-translational mechanism can inhibit neuronal hyperexcitability both in-vitro and in-vivo and a plausible link is the redox sensitive mTORC1 pathway.

Arterial spin labeling image findings in the acute phase in paediatric patients with acute encephalopathy with biphasic seizures and late reduced diffusion.

Diagnosing acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) after the first seizure (early seizure/seizures, ES/ESs) is challenging because a reduced apparent diffusion coefficient (ADC) in the cortical or subcortical white matter, often described as having a "bright-tree appearance (BTA)," is usually not observed until secondary seizures (late seizures, LSs) occur. Previous studies have reported hypoperfusion on arterial spin labeling (ASL) within 24 h after ES/ESs in patients with AESD and hyperperfusion within 24 h after LS onset. This study aimed to investigate cerebral blood flow in the hyperacute phase (between ES/ESs and LSs) using ASL in patients with AESD. Eight ASL images were acquired in six patients with AESD admitted to our hospital from October 2021 to October 2022. ASL findings in the hyperacute phase were investigated and video-electroencephalogram findings obtained around ASL image acquisition in the hyperacute phase were evaluated. Four ASL images were obtained for three patients before LS onset, with three images showing hyperperfusion areas and one image showing hypoperfusion areas. These hyperperfuion regions coincided with BTA on subsequent images of these patients.In one patient, the first ASL image was obtained in the late hyperacute phase and revealed hyperperfusion areas with a slightly abnormal change on diffusion-weighted image (DWI), which were not accompanied by ADC abnormalities. The second ASL image obtained 51 h after the first ASL, and before LS onset revealed more prominent hyperperfusion areas than the first ASL image, which were accompanied by BTA. In another patient, the ASL image obtained 82 h after ES revealed hyperperfusion areas without abnormal change on DWI or ADC. This study revealed that two patients exhibited hyperperfusion regions and another patient exhibited hypoperfusion regions among three patients who underwent ASL imaging during the period from 24 h after ES/ESs to LSs in patients with LSs or cooling initiation in patients without LSs due to early anaesthesia induction (late hyperacute phase). Further prospective studies on cerebral blood flow are required to explore the relationship among the timing of image acquisition, the presence of electrographic seizures, and ASL findings in patients with AESD.

Glioma genetic profiles associated with electrophysiologic hyperexcitability.

Distinct genetic alterations determine glioma aggressiveness, however, the diversity of somatic mutations contributing to peritumoral hyperexcitability and seizures over the course of the disease is uncertain. This study aimed to identify tumor somatic mutation profiles associated with clinically significant hyperexcitability. A single center cohort of adults with WHO grades 1-4 glioma and targeted exome sequencing (n = 1716) was analyzed and cross-referenced with a validated EEG database to identify the subset of individuals who underwent continuous EEG monitoring (n = 206). Hyperexcitability was defined by the presence of lateralized periodic discharges and/or electrographic seizures. Cross-validated discriminant analysis models trained exclusively on recurrent somatic mutations were used to identify variants associated with hyperexcitability. The distribution of WHO grades and tumor mutational burdens were similar between patients with and without hyperexcitability. Discriminant analysis models classified the presence or absence of EEG hyperexcitability with an overall accuracy of 70.9%, regardless of IDH1 R132H inclusion. Predictive variants included nonsense mutations in ATRX and TP53, indel mutations in RBBP8 and CREBBP, and nonsynonymous missense mutations with predicted damaging consequences in EGFR, KRAS, PIK3CA, TP53, and USP28. This profile improved estimates of hyperexcitability in a multivariate analysis controlling for age, sex, tumor location, integrated pathologic diagnosis, recurrence status, and preoperative epilepsy. Predicted somatic mutation variants were over-represented in patients with hyperexcitability compared to individuals without hyperexcitability and those who did not undergo continuous EEG. These findings implicate diverse glioma somatic mutations in cancer genes associated with peritumoral hyperexcitability. Tumor genetic profiling may facilitate glioma-related epilepsy prognostication and management.

Implications of intracranial hemorrhage associated with stereo-EEG

ObjectiveIntracranial hemorrhage (ICH) is a known complication during stereo-electroencephalography (sEEG) however true rates remain unknown. We provide a comprehensive review of ICH during sEEG regardless of clinical symptoms. Secondly, we analyzed sEEG recordings to identify electrographic correlates of ICH. MethodsThis is a retrospective study of patients undergoing sEEG between January 2016 and April 2022 at the Mayo Clinic in Rochester. We reviewed medical records and imaging studies to identify ICH. We analyzed ICH by type, electrode trajectories, timing, sEEG findings and outcomes. ResultsThere were a total of 201 sEEG implants, of which 23 (11%) cases or 0.9% electrodes implanted had evidence of ICH. The majority of affected patients (82%) were either asymptomatic or had mild clinical neurological manifestations. In 90% of patients who proceeded with surgical treatments, outcomes were favorable. The most common sEEG finding in contacts in proximity of ICH was either focal slowing with interictal discharges or focal electrographic seizures. ConclusionsICH associated with sEEG is likely under-reported in literature. We present electroencephalographic correlates of ICH that may aid identification of ICH in the course of performing sEEG monitoring. SignificanceOur data provides clinically relevant information on potential risks and outcomes of ICH. Furthermore, our findings aid identification of ICH during sEEG.

Amplitude Integrated Electroencephalography: Simulated Assessment of Neonatal Seizure Detection in PICU Patients.

Amplitude integrated electroencephalography (aEEG) is a mainstay of care in neonatal ICUs; however, knowledge gaps exist in relation to its accuracy for identifying seizures in older children. We aimed to review the diagnostic accuracy of existing neonatal seizure detection criteria for seizure detection in older children in hospital. Retrospective study. PICU/Neurophysiology Department in Dublin. One hundred twenty patients (2 mo to 16 yr old) were chosen from a database of formal 10-20 system, 21-lead electroencephalography recordings (2012-2020), comprising 30 studies with seizures, 90 without. None. Electroencephalography studies containing electrographic seizures (ESzs) were annotated to describe number, duration, distribution, and spread. Two-channel aEEG (using leads C3-P3, C4-P4) recordings were generated and independently reviewed by a professional specialist in clinical neurophysiology blinded to outcome and without reference to the raw electroencephalography trace. Logistic regression was used to identify factors associated with correct seizure identification on aEEG. Median patient age was 6.1 years. Abnormal recordings featured 123 seizures. Status epilepticus (SE) was evident by electroencephalography in 10 cases. Using neonatal criteria, aEEG had a sensitivity of 70% and negative predictive value of 90% for identifying any ESz. Accurate detection of individual seizures was diminished when seizures were very short or occurred during waking. Sensitivity for individual seizures was 81% when seizures less than 1 minute were excluded. aEEG correctly identified SE in 70% of the 10 cases, although ESz were confirmed to be present in 80% of this subpopulation. aEEG criteria for neonatal seizure identification can be applied with caution to older children and should be supplemented by formal electroencephalography. Seizure identification is better for longer seizures and those arising from sleep. SE is not always recognized by aEEG among older children.

Delayed Deterioration of Electroencephalogram in Patients with Cardiac Arrest: A Cohort Study.

The aim of this study was to assess the prevalence of delayed deterioration of electroencephalogram (EEG) in patients with cardiac arrest (CA) without early highly malignant patterns and to determine their associations with clinical findings. This was a retrospective study of adult patients with CA admitted to the intensive care unit (ICU) of a university hospital. We included all patients with CA who had a normal voltage EEG, no more than 10% discontinuity, and absence of sporadic epileptic discharges, periodic discharges, or electrographic seizures. Delayed deterioration was classified as the following: (1) epileptic deterioration, defined as the appearance, at least 24h after CA, of sporadic epileptic discharges, periodic discharges, and status epilepticus; or (2) background deterioration, defined as increasing discontinuity or progressive attenuation of the background at least 24h after CA. The end points were the incidence of EEG deteriorations and their association with clinical features and ICU mortality. We enrolled 188 patients in the analysis. The ICU mortality was 46%. Overall, 30 (16%) patients presented with epileptic deterioration and 9 (5%) patients presented with background deterioration; of those, two patients presented both deteriorations. Patients with epileptic deterioration more frequently had an out-of-hospital CA, and higher time to return of spontaneous circulation and less frequently had bystander resuscitation than others. Patients with background deterioration showed a predominantly noncardiac cause, more frequently developed shock, and had multiple organ failure compared with others. Patients with epileptic deterioration presented with a higher ICU mortality (77% vs. 41%; p < 0.01) than others, whereas all patients with background deterioration died in the ICU. Delayed EEG deterioration was associated with high mortality rate. Epileptic deterioration was associated with worse characteristics of CA, whereas background deterioration was associated with shock and multiple organ failure.

Diagnosis and management of seizures and myoclonus after cardiac arrest.

Cardiac arrest may lead to postanoxic brain injury. In approximately one third of the patients who remain in coma, myoclonus or status myoclonus is seen. Clinically manifest or electrographic epileptic seizures or status epilepticus are less common. Both status myoclonus and electrographic seizures indicate severe brain injury. Electroencephalography can contribute to discrimination between epileptic seizures and postanoxic myoclonus, as well as to identification of patients that may have a good outcome or can benefit from treatment. Accumulating data suggest that extensive anti-seizure treatment is futile in case of general periodic discharges. On the other hand, the small subgroup of patients with EEG patterns closely resembling electrographic seizures or status epilepticus may benefit from anti-seizure treatment, but the evidence of efficacy is weak. Medication to suppress clinically manifest myoclonus may be necessary for general ICU care and mechanical ventilation, but does not improve a patient's prognosis.

Expert and deep learning model identification of iEEG seizures and seizure onset times.

Hundreds of 90-s iEEG records are typically captured from each NeuroPace RNS System patient between clinic visits. While these records provide invaluable information about the patient's electrographic seizure and interictal activity patterns, manually classifying them into electrographic seizure/non-seizure activity, and manually identifying the seizure onset channels and times is an extremely time-consuming process. A convolutional neural network based Electrographic Seizure Classifier (ESC) model was developed in an earlier study. In this study, the classification model is tested against iEEG annotations provided by three expert reviewers board certified in epilepsy. The three experts individually annotated 3,874 iEEG channels from 36, 29, and 35 patients with leads in the mesiotemporal (MTL), neocortical (NEO), and MTL + NEO regions, respectively. The ESC model's seizure/non-seizure classification scores agreed with the three reviewers at 88.7%, 89.6%, and 84.3% which was similar to how reviewers agreed with each other (92.9%-86.4%). On iEEG channels with all 3 experts in agreement (83.2%), the ESC model had an agreement score of 93.2%. Additionally, the ESC model's certainty scores reflected combined reviewer certainty scores. When 0, 1, 2 and 3 (out of 3) reviewers annotated iEEG channels as electrographic seizures, the ESC model's seizure certainty scores were in the range: [0.12-0.19], [0.32-0.42], [0.61-0.70], and [0.92-0.95] respectively. The ESC model was used as a starting-point model for training a second Seizure Onset Detection (SOD) model. For this task, seizure onset times were manually annotated on a relatively small number of iEEG channels (4,859 from 50 patients). Experiments showed that fine-tuning the ESC models with augmented data (30,768 iEEG channels) resulted in a better validation performance (on 20% of the manually annotated data) compared to training with only the original data (3.1s vs 4.4s median absolute error). Similarly, using the ESC model weights as the starting point for fine-tuning instead of other model weight initialization methods provided significant advantage in SOD model validation performance (3.1s vs 4.7s and 3.5s median absolute error). Finally, on iEEG channels where three expert annotations of seizure onset times were within 1.5 s, the SOD model's seizure onset time prediction was within 1.7 s of expert annotation.

Non-periodic acoustic stimulation: preliminar reports of an alternative therapeutic for epilepsy

Being refractory is a significant challenge for one third of patients with epilepsy, and there is a need for new treatments. Non-periodic Stimulation (NPS) has shown promise in animal models, but it involves invasive technology. Consequently, non-invasive non-periodic Acoustic Non-periodic Stimulation (ANPS) has been developed based on NPS, with the hope that it could offer anticonvulsant effects. However, it is essential to ensure the safety of ANPS, particularly in individuals with refractory epilepsy, before it can be used in a specific application. To this end, this study aimed to assess the safety of ANPS in patients with refractory epilepsy (n=14; 8 women; 18-49 years old) using Electroencephalographic (EEG) recording and side effect evaluations over a period of five days. A questionnaire was administered immediately following the ANPS exposure and 30 days later. The study also aimed to investigate whether ANPS could trigger electrographic seizure events by counting epileptiform interictal spikes and sharp waves before and after ANPS. Additionally, the effects of ANPS on overall EEG signal properties and synchronicity were studied by calculating entropy and Phase Lock Value (PLV). Results indicate that ANPS did not trigger seizures or side effects after acute exposure or 30 days later. Rather, an improvement in quality of life and a reduction of interictal peaks and sharp waves in the EEG were observed, indicating possible anticonvulsant effects of ANPS. ANPS also increased EEG signal entropy and induced changes in brain synchrony, as evidenced by increased PLV values in some neural networks and decreased PLV values in others. Overall, these findings suggest that ANPS is well-tolerated and safe in patients with refractory epilepsy and may have anticonvulsant properties. Further investigation of its effects on neurophysiology and refractory epilepsy is warranted.

Takotsubo cardiomyopathy associated with Herpes simplex encephalitis: A case report and literature review

Takotsubo cardiomyopathy (TCM) is a stress-induced cardiomyopathy characterized by transient left ventricular dysfunction. It can be triggered by various central nervous system pathologies including status epilepticus (SE) and N-methyl-d-aspartate receptor (NMDAr) encephalitis. Herpex simplex encephalitis (HSE) is a life-threatening, sporadic, encephalitis associated with focal or global cerebral dysfunction caused by herpes simplex viruses type 1(HSV-1), or less commonly, type 2(HSV-2). While approximately 20% of patients with HSE develop NMDAr antibodies, not all manifest with encephalitis clinically. We present here a 77-year-old woman admitted with HSV-1 encephalitis who presented with acute encephalopathy and seizure-like activity. Continuous EEG monitoring (cEEG) showed periodic lateralized epileptiform discharges (PLEDs) involving the left parietotemporal region but no evidence of electrographic seizures. Her early hospital course was complicated by TCM which subsequently resolved on repeat TTE. She demonstrated initial neurological improvement. However, five weeks later her mental status declined. Again, no seizures were appreciated on cEEG. Unfortunately, repeat studies including lumbar puncture and magnetic resonance imaging (MRI) of the brain were consistent with NMDAr encephalitis. She was treated with immunosuppression and immunomodulation therapies. To our knowledge we report the first case of TCM secondary to HSE without comorbid status epilepticus. However, further studies are needed to better understand the correlation between, and underlying pathophysiology of HSE and TCM, as well as any potential association with this presentation and subsequent development of NMDAr encephalitis.