Bilateral centromedian nucleus of thalamus responsive neurostimulation for pediatric-onset drug-resistant epilepsy.

Neuromodulation therapies offer an efficacious treatment alternative for patients with drug-resistant epilepsy (DRE), particularly those unlikely to benefit from surgical resection. Here we present our retrospective single-center case series of patients with pediatric-onset DRE who underwent responsive neurostimulation (RNS) depth electrode implantation targeting the bilateral centromedian nucleus (CM) of the thalamus between October 2020 and October 2022. Sixteen patients were identified; seizure outcomes, programming parameters, and complications at follow-up were reviewed. The median age at implantation was 13 years (range 3.6-22). Six patients (38%) were younger than 12 years of age at the time of implantation. Ictal electroencephalography (EEG) patterns during patients' most disabling seizures were reliably detected. Ten patients (62%) achieved 50% or greater reduction in seizure frequency at a median 1.3 years (range 0.6-2.6) of follow-up. Eight patients (50%) experienced sensorimotor side effects, and three patients (19%) had superficial pocket infection, prompting the removal of the RNS device. Side effects of stimulation were experienced mostly in monopolar-cathodal configuration and alleviated with programming change to bipolar configuration or low-frequency stimulation. Closed-loop neurostimulation using RNS targeting bilateral CM is a feasible and useful therapy for patients with pediatric-onset DRE.

Ketogenic diet therapy for pediatric epilepsy is associated with alterations in the human gut microbiome that confer seizure resistance in mice.

The gut microbiome modulates seizure susceptibility and the anti-seizure effects of the ketogenic diet (KD) in animal models, but whether these relationships translate to KD therapies for human epilepsy is unclear. We find that the clinical KD alters gut microbial function in children with refractory epilepsy. Colonizing mice with KD-associated microbes promotes seizure resistance relative to matched pre-treatment controls. Select metagenomic and metabolomic features, including those related to anaplerosis, fatty acid ß-oxidation, and amino acid metabolism, are seen with human KD therapy and preserved upon microbiome transfer to mice. Mice colonized with KD-associated gut microbes exhibit altered hippocampal transcriptomes, including pathways related to ATP synthesis, glutathione metabolism, and oxidative phosphorylation, and are linked to susceptibility genes identified in human epilepsy. Our findings reveal key microbial functions that are altered by KD therapies for pediatric epilepsy and linked to microbiome-induced alterations in brain gene expression and seizure protection in mice.

Structural connections of the centromedian nucleus of thalamus and their relevance for neuromodulation in generalized drug-resistant epilepsy: insight from a tractography study.

Background: Epilepsy is a widespread neurologic disorder and almost one-third of patients suffer from drug-resistant epilepsy (DRE). Neuromodulation targeting the centromediannucleus of the thalamus (CM) has been showing promising results for patients with generalized DRE who are not surgical candidates. Recently, the effect of CM- deep brain stimulation (DBS) in DRE patients was investigated in the Electrical Stimulation of Thalamus for Epilepsy of Lennox-Gastaut phenotype (ESTEL) trial, a monocentric randomized-controlled study. The same authors described a 'cold-spot' and a 'sweet-spot', which are defined as the volume of stimulation in the thalamus yielding the least and the best clinical response, respectively. However, it remains unclear which structural connections may contribute to the anti-seizure effect of the stimulation. Objective: We investigated the differences in structural connectivity among CM, the sweet-spot and the cold-spot. Furthermore, we tried to validate our results in a cohort of DRE patients who underwent CM-DBS or CM-RNS (responsive neurostimulation). We hypothesized that the sweet-spot would share similar structural connectivity with responder patients. Methods: By using the software FMRIB Software Library (FSL), probabilistic tractography was performed on 100 subjects from the Human Connectome Project to calculate the probability of connectivity of the whole CM, the sweet-spot and the cold-spot to 45 cortical and subcortical areas. Results among the three seeds were compared with multivariate analysis of variance (MANOVA). Similarly, the structural connectivity of volumes of tissue activated (VTAs) from eight DRE patients was investigated. Patients were divided into responders and non-responders based on the degree of reduction in seizure frequency, and the mean probabilities of connectivity were similarly compared between the two groups. Results: The sweet-spot demonstrated a significantly higher probability of connectivity (p < 0.001) with the precentral gyrus, superior frontal gyrus, and the cerebellum than the whole CM and the cold-spot. Responder patients displayed a higher probability of connectivity with both ipsilateral (p = 0.011) and contralateral cerebellum (p = 0.04) than the non-responders. Conclusion: Cerebellar connections seem to contribute to the beneficial effects of CM-neuromodulation in patients with drug-resistant generalized epilepsy.

Characteristics of ictal thalamic EEG in pediatric-onset neocortical focal epilepsy.

OBJECTIVE: To characterize ictal EEG change in the centromedian (CM) and anterior nucleus (AN) of the thalamus, using stereoelectroencephalography (SEEG) recordings. METHODS: Forty habitual seizures were analyzed in nine patients with pediatric-onset neocortical drug-resistant epilepsy who underwent SEEG (age 2-25 y) with thalamic coverage. Both visual and quantitative analysis was used to evaluate ictal EEG signal in the cortex and thalamus. The amplitude and cortico-thalamic latencies of broadband frequencies at ictal onset were measured. RESULTS: Visual analysis demonstrated consistent detection of ictal EEG changes in both the CM nucleus and AN nucleus with latency to thalamic ictal EEG changes of less than 400 ms in 95% of seizures, with low-voltage fast activity being the most common ictal pattern. Quantitative broadband amplitude analysis showed consistent power changes across the frequency bands, corresponding to ictal EEG onset, while while ictal EEG latency was variable from -18.0 seconds to 13.2 seconds. There was no significant difference between detection of CM and AN ictal activity on visual or amplitude analysis. Four patients with subsequent thalamic responsive neurostimulation (RNS) demonstrated ictal EEG changes consistent with SEEG findings. CONCLUSIONS: Ictal EEG changes were consistently seen at the CM and AN of the thalamus during neocortical seizures. SIGNIFICANCE: It may be feasible to use a closed-loop system in the thalamus to detect and modulate seizure activity for neocortical epilepsy.

Characteristics of ictal thalamic EEG in pediatric-onset neocortical focal epilepsy.

Objective: To characterize ictal EEG change in the centromedian (CM) and anterior nucleus (AN) of the thalamus, using stereoelectroencephalography (SEEG) recordings. Methods: Forty habitual seizures were analyzed in nine patients with pediatric-onset neocortical drug-resistant epilepsy who underwent SEEG (age 2-25 y) with thalamic coverage. Both visual and quantitative analysis was used to evaluate ictal EEG signal in the cortex and thalamus. The amplitude and cortico-thalamic latencies of broadband frequencies at ictal onset were measured. Results: Visual analysis demonstrated consistent detection of ictal EEG changes in both the CM nucleus and AN nucleus with latency to thalamic ictal EEG changes of less than 400ms in 95% of seizures, with low-voltage fast activity being the most common ictal pattern. Quantitative broadband amplitude analysis showed consistent power changes across the frequency bands, corresponding to ictal EEG onset, while while ictal EEG latency was variable from -18.0 seconds to 13.2 seconds. There was no significant difference between detection of CM and AN ictal activity on visual or amplitude analysis. Four patients with subsequent thalamic responsive neurostimulation (RNS) demonstrated ictal EEG changes consistent with SEEG findings. Conclusions: Ictal EEG changes were consistently seen at the CM and AN of the thalamus during neocortical seizures. Significance: It may be feasible to use a closed-loop system in the thalamus to detect and modulate seizure activity for neocortical epilepsy.

Survey of Pediatric ICU EEG Monitoring-Reassessment After a Decade.

PURPOSE: In 2011, the authors conducted a survey regarding continuous EEG (CEEG) utilization in critically ill children. In the interim decade, the literature has expanded, and guidelines and consensus statements have addressed CEEG utilization. Thus, the authors aimed to characterize current practice related to CEEG utilization in critically ill children. METHODS: The authors conducted an online survey of pediatric neurologists from 50 US and 12 Canadian institutions in 2022. RESULTS: The authors assessed responses from 48 of 62 (77%) surveyed institutions. Reported CEEG indications were consistent with consensus statement recommendations and included altered mental status after a seizure or status epilepticus, altered mental status of unknown etiology, or altered mental status with an acute primary neurological condition. Since the prior survey, there was a 3- to 4-fold increase in the number of patients undergoing CEEG per month and greater use of written pathways for ICU CEEG. However, variability in resources and workflow persisted, particularly regarding technologist availability, frequency of CEEG screening, communication approaches, and electrographic seizure management approaches. CONCLUSIONS: Among the surveyed institutions, which included primarily large academic centers, CEEG use in pediatric intensive care units has increased with some practice standardization, but variability in resources and workflow were persistent.

Characterizing physiological high-frequency oscillations using deep learning.

Objective.Intracranially-recorded interictal high-frequency oscillations (HFOs) have been proposed as a promising spatial biomarker of the epileptogenic zone. However, HFOs can also be recorded in the healthy brain regions, which complicates the interpretation of HFOs. The present study aimed to characterize salient features of physiological HFOs using deep learning (DL).Approach.We studied children with neocortical epilepsy who underwent intracranial strip/grid evaluation. Time-series EEG data were transformed into DL training inputs. The eloquent cortex (EC) was defined by functional cortical mapping and used as a DL label. Morphological characteristics of HFOs obtained from EC (ecHFOs) were distilled and interpreted through a novel weakly supervised DL model.Main results.A total of 63 379 interictal intracranially-recorded HFOs from 18 children were analyzed. The ecHFOs had lower amplitude throughout the 80-500 Hz frequency band around the HFO onset and also had a lower signal amplitude in the low frequency band throughout a one-second time window than non-ecHFOs, resembling a bell-shaped template in the time-frequency map. A minority of ecHFOs were HFOs with spikes (22.9%). Such morphological characteristics were confirmed to influence DL model prediction via perturbation analyses. Using the resection ratio (removed HFOs/detected HFOs) of non-ecHFOs, the prediction of postoperative seizure outcomes improved compared to using uncorrected HFOs (area under the ROC curve of 0.82, increased from 0.76).Significance.We characterized salient features of physiological HFOs using a DL algorithm. Our results suggested that this DL-based HFO classification, once trained, might help separate physiological from pathological HFOs, and efficiently guide surgical resection using HFOs.

Eyelid nystagmus in a child with cardiofaciocutaneous syndrome associated with BRAF mutation.

Eyelid nystagmus, thought to reflect midbrain or hindbrain disease, is a rare condition that typically occurs in association with neurologic and neuroophthalmic abnormalities. Cardiofaciocutaneous (CFC) syndrome associated with B-raf protooncogene serine/threonine kinase (BRAF) mutation is a complex syndrome that is associated with neurologic and neuroophthalmologic abnormalities. We report the case of a 4-year-old girl with CFC syndrome with global developmental delay who was referred for evaluation of alternating exotropia, right-sided dissociated vertical deviation, bilateral upgaze nystagmus, and bilateral eyelid fluttering. Neurological work-up revealed bilateral frontocentral sharp waves without seizure activity on electroencephalogram and mild left-sided cerebral volume loss on magnetic resonance imaging. To our knowledge, this is the first reported case of eyelid nystagmus in CFC syndrome. Eyelid nystagmus warrants neurological evaluation, because it is commonly associated with significant neurological abnormalities.

Prevalence of Seizures and Risk Factors for Mortality in a Continuous Cohort of Pediatric Extracorporeal Membrane Oxygenation Patients.

OBJECTIVES: To evaluate the risk factors for mortality in pediatric extracorporeal membrane oxygenation patients. DESIGN: Retrospective, single-center study. SETTING: PICU and Pediatric cardiothoracic ICU in an urban, quaternary care center. PATIENTS: All neonatal and pediatric patients requiring extracorporeal membrane oxygenation at our institution between January 2014 and December 2018, who underwent a standardized continuous electroencephalogram neuromonitoring protocol during most of the duration of extracorporeal membrane oxygenation support. We excluded patients who had extracorporeal membrane oxygenation initiated at another institution. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Sixty-six children required extracorporeal membrane oxygenation support during this period. Four patients were excluded, three due to lack of electroencephalogram data, one with extracorporeal membrane oxygenation initiated at other institution. In the remaining 62, 11 patients (17%) had seizures, of which 5 (45%) had status epilepticus. Eight of 11 patients (72%) had exclusively electrographic seizures. A total of 33 patients (53.2%) died, of which 22 died during extracorporeal membrane oxygenation course, and one died 3 years after hospital discharge. Mean survival from extracorporeal membrane oxygenation initiation was 766.9 days (standard deviation, 691.7; median, 546.5; interquartile range 1-3, 97.7-1255.0). In multivariate analysis, increased risk of mortality was associated with the use of extracorporeal cardiopulmonary resuscitation (hazard ratio, 4.33; 95% CI, 1.75-10.72; p = 0.002), imaging findings of cerebral edema (hazard ratio, 14.31; 95% CI, 5.18-39.54; p < 0.001), high lactate level (> 100 mg/dL within 2 hr preextracorporeal membrane oxygenation) (hazard ratio, 1.22; 95% CI, 1.03-1.44; p = 0.022), and prolonged deep hypothermic circulatory arrest (hazard ratio, 3.43; 95% CI, 1.65-7.13; p < 0.001). Presence of seizures was associated with imaging findings of cerebral edema (hazard ratio, 4.16; 95% CI, 1.04-16.58; p = 0.04). CONCLUSIONS: Seizures are common in children requiring extracorporeal membrane oxygenation support, with a high rate of electrographic seizures and status epilepticus, as in prior studies. Presence of cerebral edema is both risk factor for mortality and seizures. Other risk factors for mortality include extracorporeal cardiopulmonary resuscitation, high lactate levels, and prolonged deep hypothermic circulatory arrest.

Prospective observational study: Fast ripple localization delineates the epileptogenic zone.

OBJECTIVE: To investigate spatial correlation between interictal HFOs and neuroimaging abnormalities, and to determine if complete removal of prospectively identified interictal HFOs correlates with post-surgical seizure-freedom. METHODS: Interictal fast ripples (FRs: 250-500 Hz) in 19 consecutive children with pharmacoresistant focal epilepsy who underwent extra-operative electrocorticography (ECoG) recording were prospectively analyzed. The interictal FRs were sampled at 2000 Hz and were visually identified during 10 min of slow wave sleep. Interictal FRs, MRI and FDG-PET were delineated on patient-specific reconstructed three-dimensional brain MRI. RESULTS: Interictal FRs were observed in all patients except one. Thirteen out of 18 patients (72%) exhibited FRs beyond the extent of neuroimaging abnormalities. Fifteen of 19 children underwent resective surgery, and survival analysis with log-rank test demonstrated that complete resection of cortical sites showing interictal FRs correlated with longer post-operative seizure-freedom (p < 0.01). Complete resection of seizure onset zones (SOZ) also correlated with longer post-operative seizure-freedom (p = 0.01), yet complete resection of neuroimaging abnormalities did not (p = 0.43). CONCLUSIONS: Prospective visual analysis of interictal FRs was feasible, and it seemed to accurately localize epileptogenic zones. SIGNIFICANCE: Topological extent of epileptogenic region may exceed what is discernible by multimodal neuroimaging.

Conductive Plastic Electrodes Reduce EEG Artifact During Pediatric ECMO Therapy.

PURPOSE: Extracorporeal membrane oxygenation (ECMO) is a life-saving heart and lung bypass procedure that can cause substantial EEG artifact. Continuous EEG monitoring is nonetheless a helpful neuromonitoring tool for patients receiving ECMO therapy because neurologic complications are frequent, but factors such as sedation, neuromuscular blockade, and hemodynamic instability limit clinical and radiographic evaluation. We examined whether using conductive plastic electrodes in place of conventional gold electrodes reduces artifact in clinical EEG studies of pediatric ECMO patients. METHODS: Four masked electroencephalographers assessed artifact and its impact on overall EEG interpretation in samples from 21 consecutive EEGs recorded during ECMO therapy (14 gold and 7 plastic). A spectral power analysis then quantified 50- to 70-Hz artifact in a larger group of 14 gold and 34 plastic electrode studies during ECMO and 4 non-ECMO gold electrode studies. RESULTS: The masked electroencephalographers identified less artifact (P < 0.001) and indicated greater confidence in the accuracy of EEG interpretation (P < 0.001) among studies recorded with plastic electrodes. In quantitative analyses, ECMO was associated with greater 50- to 70-Hz power among studies using gold electrodes (P < 0.001) and gold electrodes exhibited greater 50- to 70-Hz power than plastic electrodes (P < 0.001). Contrasting studies in which most of the electroencephalographers believed that interpretation was (n = 12; 7 gold and 5 plastic) or was not (n = 7; all gold) compromised by artifact, 50- to 70-Hz power was similarly higher among the compromised studies (P < 0.001). CONCLUSION: Plastic electrodes substantially reduce the burden of electrical artifact in EEG studies performed on pediatric ECMO patients and improve confidence in EEG interpretation.

Limited efficacy of the ketogenic diet in the treatment of highly refractory epileptic spasms.

PURPOSE: Numerous studies have suggested that the ketogenic diet is effective in the treatment of epileptic spasms, even in refractory cases. However, there has been very limited demonstration of prompt and complete (video-EEG confirmed) response. We set out to describe our center's experience with the ketogenic diet in the treatment of children with highly refractory epileptic spasms, with rigorous seizure outcome assessment. METHOD: Children treated with the ketogenic diet for epileptic spasms between April, 2010 and June, 2014 were retrospectively identified. Seizure burden was tabulated at baseline and after 1, 3, 6, and 12-months of ketogenic diet exposure. Adverse events were similarly ascertained. RESULTS: We identified a cohort of 22 consecutive patients who received ketogenic diet therapy, with median age of onset of epileptic spasms of 5.2 (IQR 2.0-9.0) months, with diet initiation beginning a median of 26.4 (12.5-38.7) months after onset, and following a median of 7 (IQR 5-7) treatment failures. Only 2 patients exhibited a complete response during ketogenic diet exposure, and response was more reasonably attributed to alternative therapies in both cases. A modest early reduction in seizure frequency was not sustained beyond 1 month of diet exposure. The diet was well tolerated, and continued in 6 patients with subjective and/or partial response. CONCLUSION: In contrast to prior studies reporting substantial efficacy of the ketogenic diet, our findings suggest limited efficacy, albeit in a highly refractory cohort. Prospective studies in both refractory and new-onset populations, with both video-EEG confirmation of response and rigorous cognitive outcome assessment, would be of great value to more clearly define the utility of the ketogenic diet in the treatment of epileptic spasms.

Development and validation of a seizure prediction model in critically ill children.

PURPOSE: Electrographic seizures are common in encephalopathic critically ill children, but identification requires continuous EEG monitoring (CEEG). Development of a seizure prediction model would enable more efficient use of limited CEEG resources. We aimed to develop and validate a seizure prediction model for use among encephalopathic critically ill children. METHOD: We developed a seizure prediction model using a retrospectively acquired multi-center database of children with acute encephalopathy without an epilepsy diagnosis, who underwent clinically indicated CEEG. We performed model validation using a separate prospectively acquired single center database. Predictor variables were chosen to be readily available to clinicians prior to the onset of CEEG and included: age, etiology category, clinical seizures prior to CEEG, initial EEG background category, and inter-ictal discharge category. RESULTS: The model has fair to good discrimination ability and overall performance. At the optimal cut-off point in the validation dataset, the model has a sensitivity of 59% and a specificity of 81%. Varied cut-off points could be chosen to optimize sensitivity or specificity depending on available CEEG resources. CONCLUSION: Despite inherent variability between centers, a model developed using multi-center CEEG data and few readily available variables could guide the use of limited CEEG resources when applied at a single center. Depending on CEEG resources, centers could choose lower cut-off points to maximize identification of all patients with seizures (but with more patients monitored) or higher cut-off points to reduce resource utilization by reducing monitoring of lower risk patients (but with failure to identify some patients with seizures).

Hypsarrhythmia assessment exhibits poor interrater reliability: a threat to clinical trial validity.

OBJECTIVE: Hypsarrhythmia is the classic interictal electroencephalographic pattern associated with infantile spasms, and characterized by high voltage, disorganization, and multifocal independent epileptiform discharges. Given this seemingly simple definition, one might expect excellent interrater reliability (IRR) in the identification of this pattern. Alternatively, it may be argued that assessments of voltage and disorganization are fairly subjective, and thus quite challenging in borderline cases. We sought to test the IRR of hypsarrhythmia assessment in a systematic fashion. METHODS: Six blinded pediatric electroencephalographers from four centers reviewed 22 electroencephalography (EEG) samples from patients with infantile spasms. Each sample was 5 min in duration and included only wakefulness. Raters determined if each EEG was abnormal and if hypsarrhythmia was present/absent, and characterized relevant features: voltage, organization, epileptiform discharges, slowing, interictal attenuations, symmetry, and synchrony. In addition, raters indicated their level of confidence for each assessment. Multirater kappa statistics (κ) were calculated for the assessment of hypsarrhythmia and each feature. RESULTS: Although IRR was favorable in determining whether a study was normal or abnormal (κ=0.89), reliability was unfavorable for assessment of hypsarrhythmia (κ=0.40), modified hypsarrhythmia (κ=0.47), high voltage (κ=0.37), disorganization (κ=0.22), multifocal epileptiform discharges (κ=0.68), interictal voltage attenuations (κ=0.21), slowing (κ=0.20), asymmetry (κ=0.26), and asynchrony (κ=0.08). Despite generally unsatisfactory interrater agreement, raters consistently reported high confidence in assessments. SIGNIFICANCE: This study contradicts the view that hypsarrhythmia assessment is straightforward. Even small variability in the identification of hypsarrhythmia has potentially deleterious consequences for clinical care, as its presence or absence impacts decisions to pursue high-risk and high-cost therapies. These inconsistencies may similarly confound studies in which abolition of hypsarrhythmia is an outcome measure. There is a great need for practical, reliable, and unbiased measures of hypsarrhythmia.

The ketogenic diet as broad-spectrum treatment for super-refractory pediatric status epilepticus: challenges in implementation in the pediatric and neonatal intensive care units.

Refractory status epilepticus carries significant morbidity and mortality. Recent reports have promoted the use of the ketogenic diet as an effective treatment for refractory status epilepticus. We describe our recent experience with instituting the ketogenic diet for 4 critically ill children in refractory status epilepticus, ranging in age from 9 weeks to 13.5 years after failure of traditional treatment. The ketogenic diet allowed these patients to be weaned off continuous infusions of anesthetics without recurrence of status epilepticus, though delayed ketosis and persistently elevated glucose measurements posed special challenges to effective initiation, and none experienced complete seizure cessation. The ease of sustaining myocardial function with fatty acid energy substrates compares favorably over the myocardial toxicity posed by anesthetic doses of barbiturates and contributes to the safety profile of the ketogenic diet. The ketogenic diet can be implemented successfully and safely for the treatment of refractory status epilepticus in pediatric patients.

The collective therapeutic potential of cerebral ketone metabolism in traumatic brain injury.

The postinjury period of glucose metabolic depression is accompanied by adenosine triphosphate decreases, increased flux of glucose through the pentose phosphate pathway, free radical production, activation of poly-ADP ribose polymerase via DNA damage, and inhibition of glyceraldehyde dehydrogenase (a key glycolytic enzyme) via depletion of the cytosolic NAD pool. Under these post-brain injury conditions of impaired glycolytic metabolism, glucose becomes a less favorable energy substrate. Ketone bodies are the only known natural alternative substrate to glucose for cerebral energy metabolism. While it has been demonstrated that other fuels (pyruvate, lactate, and acetyl-L-carnitine) can be metabolized by the brain, ketones are the only endogenous fuel that can contribute significantly to cerebral metabolism. Preclinical studies employing both pre- and postinjury implementation of the ketogenic diet have demonstrated improved structural and functional outcome in traumatic brain injury (TBI) models, mild TBI/concussion models, and spinal cord injury. Further clinical studies are required to determine the optimal method to induce cerebral ketone metabolism in the postinjury brain, and to validate the neuroprotective benefits of ketogenic therapy in humans.

Treatment of infantile spasms with very high dose prednisolone before high dose adrenocorticotropic hormone.

PURPOSE: This study investigated the short-term response to a standardized hormonal therapy protocol for treatment of infantile spasms. METHODS: Twenty-seven children with video electroencephalography (EEG)-confirmed infantile spasms received very high dose (8 mg/kg/day, max 60 mg/day) oral prednisolone for 2 weeks. Response (absence of both hypsarrhythmia and spasms) to prednisolone was ascertained by repeat overnight video-EEG. Responders were tapered over 2 weeks and nonresponders were immediately transitioned to high dose (150 IU/m(2)/day) intramuscular adrenocorticotropic hormone (ACTH) for two additional weeks. Response was again determined by overnight video-EEG after ACTH therapy. KEY FINDINGS: Sixty-three percent (17/27) of patients responded completely to prednisolone. Subsequently, 40% (4/10) of prednisolone nonresponders exhibited a complete response after an additional 2-week course with ACTH. Among 27 subjects with median follow-up of 13.5 months (interquartile range [IQR] 4.8-25.9), 12% (2/17) of prednisolone responders and 50% (2/4) of ACTH responders experienced a relapse between 2 and 9 months after initial response. SIGNIFICANCE: Very high dose prednisolone demonstrated significantly higher efficacy than previously reported for lower doses in prior studies. High dose ACTH may be superior to very high dose prednisolone, and in lieu of a definitive clinical trial, the choice between prednisolone and ACTH for initial treatment of infantile spasms remains controversial.

Electrographic seizures after convulsive status epilepticus in children and young adults: a retrospective multicenter study.

OBJECTIVE: To describe the prevalence, characteristics, and predictors of electrographic seizures after convulsive status epilepticus (CSE). STUDY DESIGN: This was a multicenter retrospective study in which we describe clinical and electroencephalographic (EEG) features of children (1 month to 21 years) with CSE who underwent continuous EEG monitoring. RESULTS: Ninety-eight children (53 males) with CSE (median age of 5 years) underwent subsequent continuous EEG monitoring after CSE. Electrographic seizures (with or without clinical correlate) were identified in 32 subjects (33%). Eleven subjects (34.4%) had electrographic-only seizures, 17 subjects (53.1%) had electroclinical seizures, and 4 subjects (12.5%) had an unknown clinical correlate. Of the 32 subjects with electrographic seizures, 15 subjects (46.9%) had electrographic status epilepticus. Factors associated with the occurrence of electrographic seizures after CSE were a previous diagnosis of epilepsy (P = .029) and the presence of interictal epileptiform discharges (P < .0005). The median (p25-p75) duration of stay in the pediatric intensive care unit was longer for children with electrographic seizures than for children without electrographic seizures (9.5 [3-22.5] vs 2 [2-5] days, Wilcoxon test, Z = 3.916, P = .0001). Four children (4.1%) died before leaving the hospital, and we could not identify a relationship between death and the presence or absence of electrographic seizures. CONCLUSIONS: After CSE, one-third of children who underwent EEG monitoring experienced electrographic seizures, and among these, one-third experienced entirely electrographic-only seizures. A previous diagnosis of epilepsy and the presence of interictal epileptiform discharges were risk factors for electrographic seizures.

Subclinical early posttraumatic seizures detected by continuous EEG monitoring in a consecutive pediatric cohort.

PURPOSE: Traumatic brain injury (TBI) is an important cause of morbidity and mortality in children, and early posttraumatic seizures (EPTS) are a contributing factor to ongoing acute damage. Continuous video-EEG monitoring (cEEG) was utilized to assess the burden of clinical and electrographic EPTS. METHODS: Eighty-seven consecutive, unselected (mild - severe), acute TBI patients requiring pediatric intensive care unit (PICU) admission at two academic centers were monitored prospectively with cEEG per established clinical TBI protocols. Clinical and subclinical seizures and status epilepticus (SE, clinical and subclinical) were assessed for their relation to clinical risk factors and short-term outcome measures. KEY FINDINGS: Of all patients, 42.5% (37/87) had seizures. Younger age (p = 0.002) and injury mechanism (abusive head trauma - AHT, p < 0.001) were significant risk factors. Subclinical seizures occurred in 16.1% (14/87), while 6.9% (6/87) had only subclinical seizures. Risk factors for subclinical seizures included younger age (p < 0.001), AHT (p < 0.001), and intraaxial bleed (p < 0.001). SE occurred in 18.4% (16/87) with risk factors including younger age (p < 0.001), AHT (p < 0.001), and intraaxial bleed (p = 0.002). Subclinical SE was detected in 13.8% (12/87) with significant risk factors including younger age (p < 0.001), AHT (p = 0.001), and intraaxial bleed (p = 0.004). Subclinical seizures were associated with lower discharge King's Outcome Scale for Childhood Head Injury (KOSCHI) score (p = 0.002). SE and subclinical SE were associated with increased hospital length of stay (p = 0.017 and p = 0.041, respectively) and lower hospital discharge KOSCHI (p = 0.007 and p = 0.040, respectively). SIGNIFICANCE: cEEG monitoring significantly improves detection of seizures/SE and is the only way to detect subclinical seizures/SE. cEEG may be indicated after pediatric TBI, particularly in younger children, AHT cases, and those with intraaxial blood on computerized tomography (CT).

Electroencephalography monitoring in critically ill children: current practice and implications for future study design.

PURPOSE: Survey data indicate that continuous electroencephalography (EEG) (CEEG) monitoring is used with increasing frequency to identify electrographic seizures in critically ill children, but studies of current CEEG practice have not been conducted. We aimed to describe the clinical utilization of CEEG in critically ill children at tertiary care hospitals with a particular focus on variables essential for designing feasible prospective multicenter studies evaluating the impact of electrographic seizures on outcome. METHODS: Eleven North American centers retrospectively enrolled 550 consecutive critically ill children who underwent CEEG. We collected data regarding subject characteristics, CEEG indications, and CEEG findings. KEY FINDINGS: CEEG indications were encephalopathy with possible seizures in 67% of subjects, event characterization in 38% of subjects, and management of refractory status epilepticus in 11% of subjects. CEEG was initiated outside routine work hours in 47% of subjects. CEEG duration was <12 h in 16%, 12-24 h in 34%, and >24 h in 48%. Substantial variability existed among sites in CEEG indications and neurologic diagnoses, yet within each acute neurologic diagnosis category a similar proportion of subjects at each site had electrographic seizures. Electrographic seizure characteristics including distribution and duration varied across sites and neurologic diagnoses. SIGNIFICANCE: These data provide a systematic assessment of recent CEEG use in critically ill children and indicate variability in practice. The results suggest that multicenter studies are feasible if CEEG monitoring pathways can be standardized. However, the data also indicate that electrographic seizure variability must be considered when designing studies that address the impact of electrographic seizures on outcome.