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.

The Effect of Music and White Noise on Electroencephalographic (EEG) Functional Connectivity in Neonates in the Neonatal Intensive Care Unit.

The purpose of this study is to investigate whether listening to music and white noise affects functional connectivity on scalp electroencephalography (EEG) in neonates in the neonatal intensive care unit.Nine neonates of ≥34 weeks' gestational age, who were already undergoing clinical continuous EEG monitoring in the neonatal intensive care unit, listened to lullaby-like music and white noise for 1 hour each separated by a 2-hour interval of no intervention. EEG segments during periods of music, white noise, and no intervention were band-pass filtered as delta (0.5-4 Hz), theta (4-8 Hz), lower alpha (8-10 Hz), upper alpha (10-13 Hz), beta (13-30 Hz), and gamma (30-45 Hz). Synchronization likelihood was used as a measure of connectivity between any 2 electrodes.In theta, lower alpha, and upper alpha frequency bands, the synchronization likelihood values yielded statistical significance with sound (music, white noise and no intervention) and with edge (between any 2 electrodes) factors. In theta, lower alpha, and upper alpha frequency bands, statistical significance was obtained between music and white noise (t = 3.12, 3.32, and 3.68, respectively; P < .017), and between white noise and no intervention (t = 4.51, 3.09, and 2.95, respectively, P < .017). However, there was no difference between music and no intervention.Although limited by a small sample size and the 1-time only auditory intervention, these preliminary results demonstrate the feasibility of EEG connectivity analyses even at bedside in neonates on continuous EEG monitoring in the neonatal intensive care unit. They also point to the possibility of detecting significant changes in functional connectivity related to the theta and alpha bands using auditory interventions.

Thalamocortical connectivity is enhanced following functional hemispherotomy for intractable lateralized epilepsy.

Although developmental outcomes may improve following functional hemispherotomy for lateralized, catastrophic childhood epilepsy, the neuronal processes mediating these improvements are unknown. We report the case of a 14-year-old child with neurocognitive impairment who underwent functional hemispherotomy with longitudinal resting-state fMRI. Compared with preoperative fMRI, we report significantly more robust thalamo-default mode network connectivity on postoperative neuroimaging. Furthermore, we show decreased connectivity to nodes within the disconnected hemisphere, providing direct evidence that functional interactions are dependent upon structural connectivity. Since the vascular supply to these nodes remains intact, although they are disconnected from the remainder of the brain, these findings also confirm that blood-oxygen level dependent oscillations are driven primarily by neuronal activity. The current study highlights the importance of thalamocortical interactions in the understanding of neural oscillations and cognitive function, and their impairment in childhood epilepsy.

Rapid eye movement sleep reveals epileptogenic spikes for resective surgery in children with generalized interictal discharges.

OBJECTIVE: Epilepsy surgery can be successful in children with extensive congenital or early acquired focal or hemispheric brain lesion on magnetic resonance imaging (MRI) despite generalized interictal epileptiform discharges (IEDs). The aim of this study was to assess if rapid eye movement (REM) sleep reduced generalized IEDs and revealed lateralized IEDs to identify the epileptogenic hemisphere in children with generalized IEDs and normal/subtle changes on MRI. METHODS: We studied 20 children with generalized IEDs on scalp electroencephalography (EEG) and normal/subtle changes on MRI who underwent intracranial video-EEG for epilepsy surgery. We assessed a minimum of 100 IEDs during REM, non-REM, and wakefulness, and assigned the distribution (generalized, left, or right hemisphere) to each IED. The number of lobes in the resected areas and seizure outcome were compared between 20 children with generalized IEDs and a comparison group of 28 children without generalized IEDs. RESULTS: The mean occurrence rate of generalized IEDs during REM (37%) was significantly lower than that during non-REM (67%, p < 0.001) and wakefulness (54%, p = 0.003). The number of children whose largest number of IEDs was lateralized in REM was significantly higher than that in non-REM (15 vs. 3 children, 75% vs. 15%, p < 0.001). The hemisphere with lateralized IEDs among three states corresponded with the surgical side in 16 children with generalized IEDs. Seventeen children (85%) with generalized IEDs and 27 (96%) without generalized IEDs underwent resective surgery. Multilobar resection was required for 16 children (94%) with generalized IEDs more frequently than 7 children (26%) without generalized IEDs (p < 0.001). Thirteen children (77%) with generalized IEDs and 19 (73%) without generalized IEDs were seizure-free with a mean of 3.3 years of follow-up. SIGNIFICANCE: Our study demonstrates the importance of assessing REM in children with generalized IEDs as it reveals lateralized epileptogenic spikes. Seizure freedom may be achieved with multilobar resection in these children with generalized IEDs and normal/subtle changes on MRI. Generalized IEDs in children with normal/subtle changes on MRI should not preclude surgical resection.

Steal phenomenon in Sturge-Weber syndrome imitating an ictal electroencephalography change in the contralateral hemisphere: report of 2 cases.

Infants with Sturge-Weber syndrome (SWS) are considered for surgery if they develop seizures and the seizures prove medically refractory. The authors report on 2 infants (15 and 19 months old) with SWS who underwent scalp video electroencephalography (EEG) and subsequent functional hemispherotomy for intractable partial motor seizures due to extensive left hemispheric angiomatosis. They presented with similar interictal and ictal EEG findings. Ictal EEG showed abrupt high-amplitude delta slow waves, without evolution on the contralateral hemisphere before the build-up of ictal EEG changes on the lesional hemisphere. The patients became seizure free after hemispherotomy. The ictal contralateral slow waves were not a sign of an ictal hemisphere and may indicate prominent ischemic changes resulting from a steal phenomenon of hemispheric angiomatosis during seizure.

Atypical language laterality is associated with large-scale disruption of network integration in children with intractable focal epilepsy.

Epilepsy is associated with disruption of integration in distributed networks, together with altered localization for functions such as expressive language. The relation between atypical network connectivity and altered localization is unknown. In the current study we tested whether atypical expressive language laterality was associated with the alteration of large-scale network integration in children with medically-intractable localization-related epilepsy (LRE). Twenty-three right-handed children (age range 8-17) with medically-intractable LRE performed a verb generation task in fMRI. Language network activation was identified and the Laterality index (LI) was calculated within the pars triangularis and pars opercularis. Resting-state data from the same cohort were subjected to independent component analysis. Dual regression was used to identify associations between resting-state integration and LI values. Higher positive values of the LI, indicating typical language localization were associated with stronger functional integration of various networks including the default mode network (DMN). The normally symmetric resting-state networks showed a pattern of lateralized connectivity mirroring that of language function. The association between atypical language localization and network integration implies a widespread disruption of neural network development. These findings may inform the interpretation of localization studies by providing novel insights into reorganization of neural networks in epilepsy.

Spatial relationship between fast and slow components of ictal activities and interictal epileptiform discharges in epileptic spasms.

OBJECTIVE: We analyzed the spatial distribution and concordance of fast (>10Hz) and slow (<5Hz) electroencephalogram (EEG) components of ictal activities and interictal epileptiform discharges (IIED) recorded by intracranial video EEG (IVEEG) in children with epileptic spasms (ES). METHODS: We studied eight children with ES, who underwent IVEEG before resective surgery for epilepsy. We quantified the root-mean-square (RMS) amplitude of the fast and slow components of ictal activities during ES and IIED. We compared the concordance between the spatial distributions of the fast and slow components of ES and IIED. RESULTS: There was a larger concordance between the spatial distributions of the fast and slow components in IIED than in ES (p=0.0206 and 0.0401). CONCLUSIONS: The spatial concordance between the fast and slow EEG components was significantly different between ES and IIED. SIGNIFICANCE: The mechanisms underlying the generation of slow EEG components may differ between ES and IIED. The slow EEG components of ES might indicate an extensive epileptic network involving remote symptomatic zones for ES in either the cortical or subcortical areas. The high spatial concordance between the fast and slow components of IIED suggests the involvement of a local inhibitory process within the epileptic cortex.

Pyridox(am)ine-5-Phosphate Oxidase Deficiency Treatable Cause of Neonatal Epileptic Encephalopathy With Burst Suppression: Case Report and Review of the Literature.

Pyridox(am)ine-5-phosphate oxidase deficiency is an autosomal recessive disorder of pyridoxine metabolism. Intractable neonatal epileptic encephalopathy is the classical presentation. Pyridoxal-5-phosphate or pyridoxine supplementation improves symptoms. We report a patient with myoclonic and tonic seizures at the age of 1 hour. Pyridoxal-5-phosphate was started on the first day of life and seizures stopped at the age of 3 days, but encephalopathy persisted for 4 weeks. She had normal neurodevelopmental outcome at the age of 12 months on pyridoxal-5-phosphate monotherapy. She had novel homozygous pathogenic frameshift mutation (c.448_451del;p.Pro150Argfs*27) in the PNPO gene. Long-lasting encephalopathy despite well-controlled clinical seizures does neither confirm nor exclude pyridox(am)ine-5-phosphate oxidase deficiency. Normal neurodevelopmental outcome of our patient emphasizes the importance of pyridoxal-5-phosphate treatment. Pyridox(am)ine-5-phosphate oxidase deficiency should be included in the differential diagnosis of Ohtahara syndrome and neonatal myoclonic encephalopathy as a treatable underlying cause. In addition, we reviewed the literature for pyridox(am)ine-5-phosphate oxidase deficiency and summarized herein all confirmed cases.

Asymmetrical generalized paroxysmal fast activities in children with intractable localization-related epilepsy.

BACKGROUND: Generalized paroxysmal fast activity (GPFA) consists of burst of generalized rhythmic discharges; 100-200 µV; 1-9s; 8-26 Hz; with frontal predominance; appearing during NREM sleep. GPFA was originally described as an electrographic feature of Lennox-Gastaut Syndrome (LGS). We analyzed GPFA on scalp video EEG (VEEG) in children to evaluate that GPFA presents in patients with intractable localization-related epilepsy. METHODS: We collected cases with GPFA with intractable localization-related epilepsy who underwent scalp VEEG, MRI, and magnetoencephalography (MEG) prior to intracranial video EEG (IVEEG) and surgical resection. We collected 50 epochs of GPFA per patient during the first night during scalp VEEG. We analyzed amplitude, duration and frequency of GPFA over the bilateral frontal region between surgical resection side with grid placement and non-resection side. RESULTS: We identified 14 (14%) patients with GPFA on scalp VEEG. The mean amplitude ranged from 145 to 589 µV (mean 293 µV). The mean duration ranged from 1.18 to 2.31s (mean 1.6s). The mean frequencies ranged from 9.3 to 14.7 Hz (mean 11.1 Hz). The amplitude (307 ± 156 µV) and duration (1.62 ± 0.8s) of GPFAs in all the patients over the resection side were significantly higher than those (279 ± 141 µV, 1.58 ± 0.8s) of the non-resection side (p<0.001). All nine patients who showed significant duration differences between two hemispheres (p<0.05) had longer duration of GPFA over the resection side. Eight of 12 patients who showed significant amplitude differences between two hemispheres (p<0.05) had higher amplitude of GPFA over the resection side. Four of six patients who showed significant frequency differences between two hemispheres (p<0.05) had higher frequency of GPFA over the resection side. Nine (64%) patients became seizure free after surgical resection including multilobar resections in eight patients. CONCLUSIONS: GPFA can exist in localization-related epilepsy with secondary bilateral synchrony. Although EEG shows GPFA on scalp VEEG, the precise localization of the epileptogenic zone using IVEEG could achieve the successful surgical resection.

Magnetoencephalography-guided resection of epileptogenic foci in children.

OBJECT: Resective surgery is increasingly used in the management of pediatric epilepsy. Frequently, invasive monitoring with subdural electrodes is required to adequately map the epileptogenic focus. The risks of invasive monitoring include the need for 2 operations, infection, and CSF leak. The aim of this study was to evaluate the feasibility and outcomes of resective epilepsy surgery guided by magnetoencephalography (MEG) in children who would have otherwise been candidates for electrode implantation. METHODS: The authors reviewed the records of patients undergoing resective epilepsy surgery at the Hospital for Sick Children between 2001 and 2010. They identified cases in which resections were based on MEG data and no intracranial recordings were performed. Each patient's chart was reviewed for presentation, MRI findings, MEG findings, surgical procedure, pathology, and surgical outcome. RESULTS: Sixteen patients qualified for the study. All patients had localized spike clusters on MEG and most had abnormal findings on MRI. Resection was carried out in each case based on the MEG data linked to neuronavigation and supplemented with intraoperative neuromonitoring. Overall, 62.5% of patients were seizure free following surgery, and 20% of patients experienced an improvement in seizures without attaining seizure freedom. In 2 cases, additional surgery was performed subsequently with intracranial monitoring in attempts to obtain seizure control. CONCLUSIONS: MEG is a viable alternative to invasive monitoring with intracranial electrodes for planning of resective surgery in carefully selected pediatric patients with localization-related epilepsy. Good candidates for this approach include patients who have a well-delineated, localized spike cluster on MEG that is concordant with findings of other preoperative evaluations and patients with prior brain pathologies that make the implantation of subdural and depth electrodes somewhat problematic.

High kurtosis of intracranial electroencephalogram as a marker of ictogenicity in pediatric epilepsy surgery.

OBJECTIVE: We determined whether kurtosis analysis of intracranial electroencephalogram (EEG) can estimate the localization of the epileptogenic zone. METHODS: We analyzed 29 pediatric epilepsy patients who underwent intracranial EEG before focal resective surgery. We localized the brain regions with high kurtosis, the seizure onset zone (SOZ) and the regions with high-rate, high-amplitude and long-duration interictal paroxysms ≥20 Hz. We tested correlations between the surgical resection of those regions and post-surgical seizure outcome, and correlations between kurtosis and the rate/amplitude/duration of interictal paroxysms. RESULTS: The resection of the regions with high kurtosis correlated with 1-year post-surgical seizure outcome (p=0.028) but not with 2-year outcome. Kurtosis showed more significant correlation with 1-year seizure outcome than the SOZ and the rate/amplitude/duration of interictal paroxysms. Kurtosis showed positive, independent correlations with the amplitude and duration of interictal paroxysms (p<0.0001) but not with the rate (p=0.4). CONCLUSIONS: The regions with high kurtosis provide more reliable information to predict seizure outcome than the SOZ and the regions with high-rate/amplitude and long-duration interictal paroxysms. Kurtosis reflects combined effects of the amplitude and duration of the interictal paroxysms. SIGNIFICANCE: High kurtosis suggests the regions with acquired ictogenicity within the irritative zone.

Focal resection of fast ripples on extraoperative intracranial EEG improves seizure outcome in pediatric epilepsy.

PURPOSE: High-frequency oscillations (HFOs), termed ripples at 80-200 Hz and fast ripples (FRs) at >200/250 Hz, recorded by intracranial electroencephalography (EEG), may be a valuable surrogate marker for the localization of the epileptogenic zone. We evaluated the relationship of the resection of focal brain regions containing high-rate interictal HFOs and the seizure-onset zone (SOZ) determined by visual EEG analysis with the postsurgical seizure outcome, using extraoperative intracranial EEG monitoring in pediatric patients and automated HFO detection. METHODS: We retrospectively analyzed 28 pediatric epilepsy patients who underwent extraoperative intracranial video-EEG monitoring prior to focal resection. Utilizing the automated analysis, we identified interictal HFOs during 20 min of sleep EEG and determined the brain regions containing high-rate HFOs. We investigated spatial relationships between regions with high-rate HFOs and SOZs. We compared the size of these regions, the surgical resection, and the amount of the regions with high-rate HFOs/SOZs within the resection area with seizure outcome. KEY FINDINGS: Ten patients were completely seizure-free and 18 were not at 2 years after surgery. The brain regions with high-rate ripples were larger than those with high-rate FRs (p = 0.0011) with partial overlap. More complete resection of the regions with high-rate FRs significantly correlated with a better seizure outcome (p = 0.046). More complete resection of the regions with high-rate ripples tended to improve seizure outcome (p = 0.091); however, the resection of SOZ did not influence seizure outcome (p = 0.18). The size of surgical resection was not associated with seizure outcome (p = 0.22-0.39). SIGNIFICANCE: The interictal high-rate FRs are a possible surrogate marker of the epileptogenic zone. Interictal ripples are not as specific a marker of the epileptogenic zone as interictal FRs. Resection of the brain regions with high-rate interictal FRs in addition to the SOZ may achieve a better seizure outcome.

Focal-onset myoclonic seizures and secondary bilateral synchrony.

We present a child with myoclonic seizures, epileptic spasms and generalized epileptiform discharges on scalp EEG. Magnetoencephalography and coherence-phase analysis for scalp EEG suggested focal onset in the left hemisphere. Intracranial video EEG confirmed seizure onset in the left frontal lobe with ictal high-frequency oscillations. Left frontal lobectomy suppressed his seizures. Subsets of myoclonic seizures can be focal in origin despite bilaterally synchronized epileptiform discharges on scalp EEG.

Topographic movie of intracranial ictal high-frequency oscillations with seizure semiology: epileptic network in Jacksonian seizures.

PURPOSE: We developed a technique to produce images of dynamic changes in ictal high-frequency oscillations (HFOs) >40 Hz recorded on subdural electroencephalography (EEG) that are time-locked to the ictal EEG and ictal semiology video. We applied this technique to Jacksonian seizures to demonstrate ictal HFO propagation along the homunculus in the primary sensory-motor cortex to visualize the underlying epileptic network. METHODS: We analyzed intracranial ictal EEGs from two patients with intractable Jacksonian seizures who underwent epilepsy surgery. We calculated the degrees of increase in amplitude within 40-80, 80-200, and 200-300 Hz frequency bands compared to the interictal period and converted them into topographic movies projected onto the brain surface picture. We combined these data with the ictal EEGs and video of the patient demonstrating ictal semiology. KEY FINDINGS: The ictal HFOs began in the sensory cortex and appeared concomitantly with the sensory aura. They then propagated to the motor cortex at the same time that focal motor symptoms evolved. As the seizure progressed, the ictal HFOs spread or reverberated in the rolandic region. However, even when the seizure became secondarily generalized, the ictal HFOs were confined to the rolandic region. In both cases, there was increased amplitude of higher frequency bands during seizure initiation compared to seizure progression. SIGNIFICANCE: This combined movie showed the ictal HFO propagation corresponding to the ictal semiology in Jacksonian seizures and revealed the epileptic network involved in seizure initiation and progression. This method may advance understanding of neural network activities relating to clinical seizure generation and propagation.