Add-On Deep Brain Stimulation versus Continued Vagus Nerve Stimulation for Childhood Epilepsy (ADVANCE): A Partially Randomized Patient Preference Trial.

Outcomes following vagus nerve stimulation (VNS) improve over years after implantation in children with drug-resistant epilepsy. The added value of deep brain stimulation (DBS) instead of continued VNS optimization is unknown. In a prospective, non-blinded, randomized patient preference trial of 18 children (aged 8-17 years) who did not respond to VNS after at least 1 year, add-on DBS resulted in greater seizure reduction compared with an additional year of VNS optimization (51.9% vs. 12.3%, p = 0.047). Add-on DBS also resulted in less bothersome seizures (p = 0.03), but no change in quality of life. DBS may be considered earlier for childhood epilepsy after non-response to VNS. ANN NEUROL 2024;96:405-411.

A Video is Worth a Thousand Words: The Use of Home Videos in Pediatric Neurology.

The use of home video recordings (HVRs) may aid in the diagnosis of neurological disorders. However, this practice remains underutilized. Through an anonymous survey, we sought to understand the perspectives of healthcare providers regarding the sharing of HVRs alongside referrals for responsive and economical pediatric neurology care. This was timely given COVID-19 has worsened wait times for diagnosis and consequently treatment. Most providers agree that sharing of HVRs improves patient care (93.1%: 67/73) and prevents both additional investigations (67%: 49/73) and hospital admissions (68.5%: 50/73). However, a minority of providers (21.9 %: 16/73) currently share HVRs alongside their referrals.

Which is more deleterious to cognitive performance? Interictal epileptiform discharges vs anti-seizure medication.

Children with epilepsy commonly have comorbid neurocognitive impairments that severely affect their psychosocial well-being, education, and future career prospects. Although the provenance of these deficits is multifactorial, the effects of interictal epileptiform discharges (IEDs) and anti-seizure medications (ASMs) are thought to be particularly severe. Although certain ASMs can be leveraged to inhibit IED occurrence, it remains unclear whether epileptiform discharges or the medications themselves are most deleterious to cognition. To examine this question, 25 children undergoing invasive monitoring for refractory focal epilepsy performed one or more sessions of a cognitive flexibility task. Electrophysiological data were recorded to detect IEDs. Between repeated sessions, prescribed ASMs were either continued or titrated to <50% of the baseline dose. Hierarchical mixed-effects modeling assessed the relationship between task reaction time (RT), IED occurrence, ASM type, and dose while controlling for seizure frequency. Both presence (ß ± SE = 49.91 ± 16.55 ms, p = .003) and number of IEDs (ß ± SE = 49.84 ± 12.51 ms, p < .001) were associated with slowed task RT. Higher dose oxcarbazepine significantly reduced IED frequency (p = .009) and improved task performance (ß ± SE = -107.43 ± 39.54 ms, p = .007). These results emphasize the neurocognitive consequences of IEDs independent of seizure effects. Furthermore, we demonstrate that inhibition of IEDs following treatment with select ASMs is associated with improved neurocognitive function.

Epilepsy disrupts hippocampal phase precision and impairs working memory.

OBJECTIVE: Working memory deficits are prevalent in childhood epilepsy. Working memory processing is thought to be supported by the phase of hippocampal neural oscillations. Disruptions in working memory have previously been linked to the occurrence of transient epileptic activity. This study aimed to resolve the associations between oscillatory neural activity, transient epileptiform events, and working memory in children with epilepsy. METHODS: Intracranial recordings were acquired from stereotactically implanted electrodes in the hippocampi, epileptogenic zones, and working memory-related networks of children with drug-resistant epilepsy during a 1-back working memory task. Interictal epileptic activity was captured using automated detectors. Hippocampal phase and interregional connectivity within working memory networks were indexed by Rayleigh Z and the phase difference derivative, respectively. Trials with and without transient epileptiform events were compared. RESULTS: Twelve children (mean age = 14.3 ± 2.8 years) with drug-resistant epilepsy were included in the study. In the absence of transient epileptic activity, significant delta and theta hippocampal phase resetting occurred in response to working memory stimulus presentation (Rayleigh z-score = 9, Rayleigh z-score = 8). Retrieval trials that were in phase with the preferred phase angle were associated with faster reaction times (p = .01, p = .03). Concurrently, delta and theta coordinated interactions between the hippocampi and working memory-related networks were enhanced (phase difference derivative [PDD] z-scores = 6-11). During retrieval trials with pre-encoding or pre-retrieval transient epileptic activity, phase resetting was attenuated (Rayleigh z-score = 5, Rayleigh z-score = 1), interregional connectivity was altered (PDD z-scores = 1-3), and reaction times were prolonged (p = .01, p = .03). SIGNIFICANCE: This work highlights the role of hippocampal phase in working memory. We observe poststimulus hippocampal phase resetting coincident with enhanced interregional connectivity. The precision of hippocampal phase predicts optimal working memory processing, and transient epileptic activity prolongs working memory processing. These findings can help guide future treatments aimed at restoring memory function in this patient population.

Interictal discharges delay target-directed eye movements and impair attentional set-shifting in children with epilepsy.

OBJECTIVE: The theory of transient cognitive impairment in epilepsy posits that lapses in attention result from ephemeral disruption of attentional circuitry by interictal events. Eye movements are intimately associated with human attention and can be monitored in real time using eye-tracking technologies. Here, we sought to characterize the associations between interictal epileptiform discharges (IEDs), gaze, and attentional behavior in children with epilepsy. METHODS: Eleven consecutive children undergoing invasive monitoring with stereotactic electrodes for localization-related epilepsy performed an attentional set-shifting task while tandem intracranial electroencephalographic signals and eye-tracking data were recorded. Using an established algorithm, IEDs were detected across all intracranial electrodes on a trial-by-trial basis. Hierarchical mixed-effects modeling was performed to delineate associations between trial reaction time (RT), eye movements, and IEDs. RESULTS: Hierarchical mixed-effects modeling revealed that both the presence of an IED (ß ± SE = 72.74 ± 24.21 ms, p = .003) and the frequency of epileptiform events (ß ± SE = 67.54 ± 17.30 ms, p < .001) were associated with prolonged RT on the attentional set-shifting task. IED occurrence at the time of stimulus presentation was associated with delays in gaze initiation toward the visual targets (p = .017). SIGNIFICANCE: The occurrence of epileptiform activity in close temporal association with stimulus presentation is associated with delays in target-directed gaze and prolonged response time, hallmarks of momentary lapses in attention. These findings provide novel insights into the mechanisms of transient impairments in children and support the use of visual tracking as a correlate of higher order attentional behavior.

Phase Resetting in the Anterior Cingulate Cortex Subserves Childhood Attention and Is Impaired by Epilepsy.

The neural mechanisms that underlie selective attention in children are poorly understood. By administering a set-shifting task to children with intracranial electrodes stereotactically implanted within anterior cingulate cortex (ACC) for epilepsy monitoring, we demonstrate that selective attention in a set-shifting task is dependent upon theta-band phase resetting immediately following stimulus onset and that the preferred theta phase angle is predictive of reaction time during attentional shift. We also observe selective enhancement of oscillatory coupling between the ACC and the dorsal attention network and decoupling with the default mode network during task performance. When transient focal epileptic activity occurs around the time of stimulus onset, phase resetting is impaired, connectivity changes with attentional and default mode networks are abolished, and reaction times are prolonged. The results of the present work highlight the fundamental mechanistic role of oscillatory phase in ACC in supporting attentional circuitry and present novel opportunities to remediate attention deficits in children with epilepsy.

Spectral changes following resective epilepsy surgery and neurocognitive function in children with epilepsy.

Decelerated resting cortical oscillations, high-frequency activity, and enhanced cross-frequency interactions are features of focal epilepsy. The association between electrophysiological signal properties and neurocognitive function, particularly following resective surgery, is, however, unclear. In the current report, we studied intraoperative recordings from intracranial electrodes implanted in seven children with focal epilepsy and analyzed the spectral dynamics both before and after surgical resection of the hypothesized seizure focus. The associations between electrophysiological spectral signatures and each child's neurocognitive profiles were characterized using a partial least squares analysis. We find that extent of spectral alteration at the periphery of surgical resection, as indexed by slowed resting frequency and its acceleration following surgery, is associated with baseline cognitive deficits in children. The current report provides evidence supporting the relationship between altered spectral properties in focal epilepsy and neuropsychological deficits in children. In particular, these findings suggest a critical role of disrupted thalamocortical rhythms, which are believed to underlie the spectral alterations we describe, in both epileptogenicity and neurocognitive function.NEW & NOTEWORTHY Spectral alterations marked by decelerated resting oscillations and ectopic high-frequency activity have been noted in focal epilepsy. We leveraged intraoperative recordings from chronically implanted electrodes pre- and postresection to understand the association between these electrophysiological phenomena and neuropsychological function. We find that the extent of spectral alteration, indexed by slowed resting frequency and its acceleration following resection, is associated with baseline cognitive deficits. These findings provide novel insights into neurocognitive impairments in focal epilepsy.

Seizure Detection Algorithms in Critically Ill Children: A Comparative Evaluation.

OBJECTIVES: To evaluate the performance of commercially available seizure detection algorithms in critically ill children. DESIGN: Diagnostic accuracy comparison between commercially available seizure detection algorithms referenced to electroencephalography experts using quantitative electroencephalography trends. SETTING: Multispecialty quaternary children's hospital in Canada. SUBJECTS: Critically ill children undergoing electroencephalography monitoring. INTERVENTIONS: Continuous raw electroencephalography recordings (n = 19) were analyzed by a neurophysiologist to identify seizures. Those recordings were then converted to quantitative electroencephalography displays (amplitude-integrated electroencephalography and color density spectral array) and evaluated by six independent electroencephalography experts to determine the sensitivity and specificity of the amplitude-integrated electroencephalography and color density spectral array displays for seizure identification in comparison to expert interpretation of raw electroencephalography data. Those evaluations were then compared with four commercial seizure detection algorithms: ICTA-S (Stellate Harmonie Version 7; Natus Medical, San Carlos, CA), NB (Stellate Harmonie Version 7; Natus Medical), Persyst 11 (Persyst Development, Prescott, AZ), and Persyst 13 (Persyst Development) to determine sensitivity and specificity in comparison to amplitude-integrated electroencephalography and color density spectral array. MEASUREMENTS AND MAIN RESULTS: Of the 379 seizures identified on raw electroencephalography, ICTA-S detected 36.9%, NB detected 92.3%, Persyst 11 detected 75.9%, and Persyst 13 detected 74.4%, whereas electroencephalography experts identified 76.5% of seizures using color density spectral array and 73.7% using amplitude-integrated electroencephalography. Daily false-positive rates averaged across all recordings were 4.7 with ICTA-S, 126.3 with NB, 5.1 with Persyst 11, 15.5 with Persyst 13, 1.7 with color density spectral array, and 1.5 with amplitude-integrated electroencephalography. Both Persyst 11 and Persyst 13 had sensitivity comparable to that of electroencephalography experts using amplitude-integrated electroencephalography and color density spectral array. Although Persyst 13 displayed the highest sensitivity for seizure count and seizure burden detected, Persyst 11 exhibited the best trade-off between sensitivity and false-positive rate among all seizure detection algorithms. CONCLUSIONS: Some commercially available seizure detection algorithms demonstrate performance for seizure detection that is comparable to that of electroencephalography experts using quantitative electroencephalography displays. These algorithms may have utility as early warning systems that prompt review of quantitative electroencephalography or raw electroencephalography tracings, potentially leading to more timely seizure identification in critically ill patients.

Connectomic Profiling Identifies Responders to Vagus Nerve Stimulation.

OBJECTIVE: Vagus nerve stimulation (VNS) is a common treatment for medically intractable epilepsy, but response rates are highly variable, with no preoperative means of identifying good candidates. This study aimed to predict VNS response using structural and functional connectomic profiling. METHODS: Fifty-six children, comprising discovery (n = 38) and validation (n = 18) cohorts, were recruited from 3 separate institutions. Diffusion tensor imaging was used to identify group differences in white matter microstructure, which in turn informed beamforming of resting-state magnetoencephalography recordings. The results were used to generate a support vector machine learning classifier, which was independently validated. This algorithm was compared to a second classifier generated using 31 clinical covariates. RESULTS: Treatment responders demonstrated greater fractional anisotropy in left thalamocortical, limbic, and association fibers, as well as greater connectivity in a functional network encompassing left thalamic, insular, and temporal nodes (p < 0.05). The resulting classifier demonstrated 89.5% accuracy and area under the receiver operating characteristic (ROC) curve of 0.93 on 10-fold cross-validation. In the external validation cohort, this model demonstrated an accuracy of 83.3%, with a sensitivity of 85.7% and specificity of 75.0%. This was significantly superior to predictions using clinical covariates alone, which exhibited an area under the ROC curve of 0.57 (p < 0.008). INTERPRETATION: This study provides the first multi-institutional, multimodal connectomic prediction algorithm for VNS, and provides new insights into its mechanism of action. Reliable identification of VNS responders is critical to mitigate surgical risks for children who may not benefit, and to ensure cost-effective allocation of health care resources. ANN NEUROL 2019;86:743-753.

Temporal-plus epilepsy in children: A connectomic analysis in magnetoencephalography.

OBJECTIVE: Seizure recurrence following surgery for temporal lobe (TL) epilepsy may be related to extratemporal epileptogenic foci, so-called temporal-plus (TL+) epilepsy. Here, we sought to leverage whole brain connectomic profiling in magnetoencephalography (MEG) to identify neural networks indicative of TL+ epilepsy in children. METHODS: Clinical and MEG data were analyzed for 121 children with TL and TL+ epilepsy spanning 20 years at the Hospital for Sick Children. Resting-state connectomes were derived using the weighted phase lag index from neuromagnetic oscillations. Multidimensional associations between patient connectomes, TL versus TL+ epilepsy, seizure freedom, and clinical covariates were performed using a partial least squares (PLS) analysis. Bootstrap resampling statistics were performed to assess statistical significance. RESULTS: A single significant latent variable representing 66% of the variance in the data was identified with significant contributions from extent of epilepsy (TL vs TL+), duration of illness, and underlying etiology. This component was associated with significant bitemporal and frontotemporal connectivity in the theta, alpha, and beta bands. By extracting a brain score, representative of the observed connectivity profile, patients with TL epilepsy were dissociated from those with TL+, independent of their postoperative seizure outcome. SIGNIFICANCE: By analyzing 121 connectomes derived from MEG data using a PLS approach, we find that connectomic profiling could dissociate TL from TL+ epilepsy. These findings may inform patient selection for resective procedures and guide decisions surrounding invasive monitoring.

KCNT1-related epilepsy: An international multicenter cohort of 27 pediatric cases.

OBJECTIVE: Through international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1-related epilepsy and explored genotype-phenotype correlations associated with frequently encountered variants. METHODS: A cross-sectional analysis of children harboring pathogenic or likely pathogenic KCNT1 variants was completed. Children with one of the two more common recurrent KCNT1 variants were compared with the rest of the cohort for the presence of particular characteristics. RESULTS: Twenty-seven children (15 males, mean age = 40.8 months) were included. Seizure onset ranged from 1 day to 6 months, and half (48.1%) exhibited developmental plateauing upon onset. Two-thirds had epilepsy of infancy with migrating focal seizures (EIMFS), and focal tonic seizures were common (48.1%). The most frequent recurrent KCNT1 variants were c.2800G>A; p.Ala934Thr (n = 5) and c.862G>A; p.Gly288Ser (n = 4). De novo variants were found in 96% of tested parents (23/24). Sixty percent had abnormal magnetic resonance imaging (MRI) findings. Delayed myelination, thin corpus callosum, and brain atrophy were the most common. One child had gray-white matter interface indistinctness, suggesting a malformation of cortical development. Several antiepileptic drugs (mean = 7.4/patient) were tried, with no consistent response to any one agent. Eleven tried quinidine; 45% had marked (>50% seizure reduction) or some improvement (25%-50% seizure reduction). Seven used cannabidiol; 71% experienced marked or some improvement. Fourteen tried diet therapies; 57% had marked or some improvement. When comparing the recurrent variants to the rest of the cohort with respect to developmental trajectory, presence of EIMFS, >500 seizures/mo, abnormal MRI, and treatment response, there were no statistically significant differences. Four patients died (15%), none of sudden unexpected death in epilepsy. SIGNIFICANCE: Our cohort reinforces common aspects of this highly pleiotropic entity. EIMFS manifesting with refractory tonic seizures was the most common. Cannabidiol, diet therapy, and quinidine seem to offer the best chances of seizure reduction, although evidence-based practice is still unavailable.

Autonomic dysregulation in children with epilepsy with postictal generalized EEG suppression following generalized convulsive seizures.

OBJECTIVE: Postictal generalized electroencephalographic suppression (PGES) has been associated with sudden unexpected death in epilepsy (SUDEP) in adults. Decreased heart rate variability (HRV) is one clinical marker of SUDEP in adults with epilepsy. The objective of this study was to analyze the characteristics of HRV associated with generalized convulsive seizures (GCS) ±â€¯PGES in children. METHODS: Nine hundred and seventy-seven consecutive children who underwent prolonged scalp video-EEG (vEEG) and 1-lead electrocardiogram (ECG) monitoring at the Hospital for Sick Children, Toronto, Ontario, Canada were reviewed retrospectively from 2009 to 2011. Thirty-five children had GCS captured during their vEEG with or without PGES and met inclusion criteria. Children were subdivided into three age groups and compared with age-matched controls: 3-6 years; 7-12 years; and 13-18 years. Interictal HRV was measured at 5 min during N2 sleep. Preictal HRV was measured at 1 h prior to GCS onset, and postictal HRV was measured at 3 min post-GCS cessation. Low frequency (LF: ms2, 0.04-0.15 Hz) and high frequency (HF: ms2, 0.15-0.4 Hz) bands of heart rate oscillations were analyzed during the interictal and preictal periods. The root mean square of successive differences (RMSSDs) was analyzed during the following time points: interictal; preictal; and postictal. RESULTS: Thirty-five children had GCS: 18 children with PGES [3-6 years (n = 2); 7-12 years (n = 6); 13-18 years (n = 10)] and 17 children without PGES [3-6 years (n = 6); 7-12 years (n = 5); 13-18 years (n = 6)]. Seventeen additional age-matched controls were identified [3-6 years (n = 3); 7-12 years (n = 5); 13-18 years (n = 9)]. Seventy-four GCS were captured consisting of 36 GCS + PGES and 38 GCS - PGES. There was no difference of interictal HRV among children with GCS ±â€¯PGES and controls. The preictal LF and HF in 36 GCS + PGES were significantly higher compared with 38 GCS - PGES (p < 0.01). The postictal RMSSD in 36 GCS + PGES was significantly higher compared with 38 GCS - PGES (p < 0.01). The pre- to postictal RMSSD change was significantly lower in children with GCS + PGES than in those with GCS - PGES (p = 0.035). CONCLUSIONS: In summary, the preictal HRV in GCS + PGES was significantly higher than in children with GCS - PGES. The higher remaining postictal RMSSD in children with GCS + PGES is a potential indicator of autonomic dysregulation. In certain children with epilepsy, autonomic dysregulation may contribute to poor recovery from a GCS with subsequent PGES, thereby contributing to SUDEP. Heart rate variability and autonomic regulation in children with epilepsy should be further studied prospectively in order to better understand the mechanism by which PGES may lead to SUDEP.

Thalamocortical dysrhythmia in intraoperative recordings of focal epilepsy.

Resonant interactions between the thalamus and cortex subserve a critical role for maintenance of consciousness as well as cognitive functions. In states of abnormal thalamic inhibition, thalamocortical dysrhythmia (TCD) has been described. The characteristics of TCD include a slowing of resting oscillations, ectopic high-frequency activity, and increased cross-frequency coupling. Here, we demonstrate the presence of TCD in four patients who underwent resective epilepsy surgery with chronically implanted electrodes under anesthesia, continuously recording activity from brain regions at the periphery of the epileptogenic zone before and after resection. Following resection, we report an acceleration of the large-scale network resting frequency coincident with decreases in cross-frequency phase-amplitude coupling. Interregional functional connectivity in the surrounding cortex was also increased following resection of the epileptogenic focus. These findings provide evidence for the presence of TCD in focal epilepsy and highlight the importance of reciprocal thalamocortical oscillatory interactions in defining novel biomarkers for resective surgeries. NEW & NOTEWORTHY Thalamocortical dysrhythmia (TCD) occurs in the context of thalamic dysfacilitation and is characterized by slowing of resting oscillations, ectopic high-frequency activity, and cross-frequency coupling. We provide evidence for TCD in focal epilepsy by studying electrophysiological changes occurring at the periphery of the resection margin. We report acceleration of resting activity coincident with decreased cross-frequency coupling and increased functional connectivity. The study of TCD in epilepsy has implications as a biomarker and therapeutic target.

EEG before and after total corpus callosotomy for pharmacoresistant infantile spasms: Fast oscillations and slow-wave connectivity in hypsarrhythmia.

OBJECTIVE: We analyzed the features of fast oscillations (FOs) and connectivity in hypsarrhythmia to identify biomarkers for predicting seizure outcomes after total corpus callosotomy (TCC) in children with pharmacoresistant infantile spasms (IS). We hypothesize that the power of FOs and connectivity of slow waves in hypsarrhythmia would indicate the prognosis of IS. METHOD: We retrospectively identified 42 children with pharmacoresistant IS who underwent TCC from 2009 to 2014 at Nagasaki Medical Center. We collected preoperative hypsarrhythmia for 200 seconds from each child. Children were categorized into three groups with interictal epileptic discharges on EEG at 6 months after TCC: group A, no epileptic discharge; group B, lateralized epileptic discharges; and group C; bilateral epileptic discharges. We analyzed spectral power and phase synchronization in preoperative hypsarrhythmia among the three groups. RESULTS: We found 10 children in group A, 10 children in group B, and 22 children in group C. All group A and 1 in group B achieved seizure freedom after TCC. Six (67%) of 9 group B children who underwent further surgeries achieved seizure freedom. Ten (45%) of group C children had seizure reduction >50% after TCC, and 13 (87%) of 15 children who underwent further surgeries had residual seizures. The clinical profiles of the three groups did not differ significantly. The power of FOs (≥45 Hz) in hypsarrhythmia was significantly stronger in group C at the midline and temporal regions than in groups B and A (P = .014). The connectivity of theta (4-9 Hz) and FOs (29-70 Hz) tended to increase in group C, compared with the increased connectivity of 1-2 Hz in group A (P = .08). SIGNIFICANCE: The increased power and connectivity of FOs in hypsarrhythmia may correlate with pharmacoresistant and surgically resistant seizures in IS. The existence and connectivity of FOs are associated with unilateral/bilateral cortical epileptogenicity in hypsarrhythmia. Prominent slow waves and connectivity without FOs might correlate with seizure freedom after TCC. Modulation of the callosal system with subcortical/cortical epileptic discharges might play a role in generating hypsarrhythmia and IS.

Low entropy of interictal gamma oscillations is a biomarker of the seizure onset zone in focal cortical dysplasia type II.

OBJECTIVE: Dynamic changes in the regularity of interictal gamma oscillations (GOs, 30-70 Hz) on intracranial electroencephalography (EEG) reflect focal ictogenesis with epileptogenic neuronal synchronization in focal cortical dysplasia (FCD). We investigated whether the regularity of interictal GOs is a biomarker of the seizure onset zone (SOZ) using multiscale entropy analysis. METHODS: We quantified the regularity of interictal GOs using intracranial EEG data from 1164 electrodes in 13 patients with FCD who were seizure-free postoperatively. The regularity of interictal GOs was quantified as entropy values. Low entropy represents high regularity. We standardized entropy values using Z values for each SOZ, resection area (RA), and the region outside the RA. The cutoff Z values, sensitivity, and specificity for detecting each area were calculated using area under the receiver operating characteristics curves (AUCs). RESULTS: Low Z values represent higher regularity of GOs. The cutoff Z value of ≤-2.09 for the SOZ had a sensitivity of 100% and specificity of 97.1% (AUC = 0.992 ±â€¯0.002). The cutoff Z value of ≤-0.12 for the RA had a sensitivity of 54.2% and specificity of 73.8% (AUC = 0.673 ±â€¯0.019). The cutoff Z value of ≥-0.11 for the region outside the RA had a sensitivity of 73.8% and specificity of 54.2% (AUC = 0.673 ±â€¯0.019). CONCLUSIONS: Low entropy of interictal GOs was a reliable biomarker for the SOZ. Maintained high entropy of interictal GOs may be an auxiliary biomarker for nonepileptogenic regions. SIGNIFICANCE: Low entropy of interictal GOs may be a biomarker for the SOZ in FCD type II.

Sudden unexpected death in epilepsy in the bathtub.

OBJECTIVE: Sudden death in the bathtub occurs relatively frequently in Japan, particularly among elderly people. We hypothesize that sudden death in epilepsy occurring in the bathtub (SDEPB) can be distinguished from sudden death in nonepilepsy occurring in the bathtub (SDnonEPB), but is identical to sudden unexpected death in epilepsy (SUDEP). METHODS: Tokyo Medical Examiner's Office conducts postmortem examinations for all sudden and unexpected deaths in Tokyo. Clinical, social, and autopsy findings of 43 SDEPB were compared with 76 SDnonEPB, 50 SUDEP outside the bathtub, and Japanese forensic autopsy data as controls. RESULTS: Extension of the leg(s) outside the bathtub was seen in 33% of SDEPB, but none of SDnonEPB. Sitting position was seen less frequently in SDEPB (37%) than in SDnonEPB (64%). Lung weight and pleural effusion volume were significantly lower in SDEPB than in SDnonEPB. Age at death in SDEPB was significantly younger than that in SDnonEPB. Sudden death in epilepsy occurring in the bathtub showed no differences in lung weight and pleural effusion volume from SUDEP. Living with family was more frequent in SDEPB (73%) than in SUDEP (48%). Few antiepileptic drugs, infrequent seizures, and low rate of mental retardation were identical between SDEPB and SUDEP. Lung weight was significantly heavier in all three groups than in age- and sex- matched autopsy controls. CONCLUSIONS: Leg extension outside the bathtub, lower lung weight, and absence of pleural effusion distinguish SDEPB from SDnonEPB in elderly people. Sudden death in epilepsy occurring in the bathtub may represent a form of SUDEP occurring in the bathtub, rather than drowning despite submergence in the bathtub at discovery. Conditions for bathing require careful attention from physicians and relatives, even for patients with epilepsy with few medications and infrequent seizures, and without mental retardation.

Magnetic Source Imaging Localization of 14 and 6 Hz Positive Bursts.

A 16-year-old boy with learning disability presented with nocturnal pharmaco-resistant focal seizures consisting of right arm/axilla pain, sometimes followed by tonic-clonic movements of right arm/leg since 8 years of age. He was on valproate and levetiracetam and had failed multiple drugs in the past. Family history and examination were unremarkable.

The role of surgery in refractory epilepsy secondary to polymicrogyria in the pediatric population.

OBJECTIVE: Polymicrogyria (PMG) is a common malformation of cortical development. Many patients with PMG will have medically refractory epilepsy but the role of epilepsy surgery is unclear. The objective of this study was to assess the efficacy of surgical resection/disconnection in achieving seizure control in pediatric patients with PMG. METHODS: A retrospective review of children undergoing epilepsy surgery for PMG between 2002 and 2017 at The Hospital for Sick Children in Toronto, Canada, was performed. RESULTS: A total of 12 children aged 6 months to 17.8 years (median 8.8 years) underwent resective surgery (7 children) or functional hemispherectomy (5 children). Gross total resection or complete disconnection of PMG was carried out in 7 of 12 children. Follow-up duration was between 1 and 9 years (median 2.1 years). Nine children remained seizure-free at last follow-up. Complete resection or disconnection of PMG led to seizure freedom in 6 of 7 patients (86%), whereas subtotal resection produced seizure freedom in 3 of 5 patients (60%). SIGNIFICANCE: We present one of the largest surgical series of pediatric PMG patients. Seizure outcomes were best with complete resection/disconnection of PMG. However, tailored resections based on electroclinical and neuroradiologic data can produce good outcomes and remain an appropriate strategy for patients with extensive PMG.

Strong coupling between slow oscillations and wide fast ripples in children with epileptic spasms: Investigation of modulation index and occurrence rate.

OBJECTIVE: Epileptic spasms (ES) often become drug-resistant. To reveal the electrophysiological difference between children with ES (ES+) and without ES (ES-), we compared the occurrence rate (OR) of high-frequency oscillations (HFOs) and the modulation index (MI) of coupling between slow and fast oscillations. In ES+, we hypothesized that (1) pathological HFOs are more widely distributed and (2) slow oscillations show stronger coupling with pathological HFOs than in ES-. METHODS: We retrospectively reviewed 24 children with drug-resistant multilobar onset epilepsy, who underwent intracranial video electroencephalography prior to multilobar resections. We measured the OR of HFOs and determined the electrodes with a high rate of HFOs by cluster analysis. We calculated MI, which reflects the degree of coupling between HFO (ripple/fast ripple [FR]) amplitude and 5 different frequency bands of delta and theta activities (0.5-1 Hz, 1-2 Hz, 2-3 Hz, 3-4 Hz, 4-8 Hz). RESULTS: In ES+ (n = 10), the OR(FRs) , the number of electrodes with high-rate FRs, and the MI(FRs & 3-4 Hz) in all electrodes were significantly higher than in ES- (n = 14). In both the ES+ and ES- groups, MI(ripples/FRs & 3-4 Hz) was the highest among the 5 frequency bands. Within the good seizure outcome group, the OR(FRs) and the MI(FRs & 3-4 Hz) in the resected area in ES+ were significantly higher than in ES- (OR[FRs] , P = .04; MI[FRs & 3-4 Hz] , P = .04). SIGNIFICANCE: In ES+, the larger number of high-rate FR electrodes indicates more widespread epileptogenicity than in ES-. High values of OR(FRs) and MI(FRs & 3-4 Hz) in ES+ compared to ES- are a signature of the severity of epileptogenicity. We proved that ES+ children who achieved seizure freedom following multilobar resections exhibited strong coupling between slow oscillations and FRs.

Children with autism spectrum disorders and drug-resistant epilepsy can benefit from epilepsy surgery.

OBJECTIVE: The objective of this research was to evaluate a cohort of children with both autism spectrum disorder (ASD) and drug-resistant epilepsy (DRE) after epilepsy surgery to determine predictors of best outcome. METHODS: Retrospective chart review was done for 29 children ages 2 to 18 years with ASD and DRE who had neurosurgical intervention for seizure management over 15 years at one institution. All subjects had at least 1 year of follow-up. Data abstraction included demographic information, seizure diagnosis, treatment, investigations, surgical intervention, neuropsychological assessment, and outcome. Statistical analysis software (SAS) was used for statistical analysis. Engel classification was used to assess seizure outcome. RESULTS: Fifteen subjects had resective surgery. Fourteen had palliative surgery with vagal nerve stimulator (VNS) insertion (13) and corpus callosotomy (1). Of the 29 subjects, 35% had class I outcome (all in the resective group). When combining all subjects (resective and palliative), 66% of subjects benefited with class I-III outcomes. In the total cohort, age at time of surgery was significant, with class I outcome more frequently seen in the younger age group when compared with classes II-IV (p = 0.01). CONCLUSION: A subset of children with ASD can benefit from resective surgery, and for those who are not candidates, a VNS can offer significant improvements in seizure control.