Intraoperative changes in large-scale thalamic circuitry following laser ablation of hypothalamic hamartomas.

BACKGROUND AND OBJECTIVES: Gelastic seizures due to hypothalamic hamartomas (HH) are challenging to treat, in part due to an incomplete understanding of seizure propagation pathways. Although magnetic resonance imaging-guided laser interstitial thermal therapy (MRgLITT) is a promising intervention to disconnect HH from ictal propagation networks, the optimal site of ablation to achieve seizure freedom is not known. In this study, we investigated intraoperative post-ablation changes in resting-state functional connectivity to identify large-scale networks associated with successful disconnection of HH. METHODS: Children who underwent MRgLITT for HH at two institutions were consecutively recruited and followed for a minimum of one year. Seizure freedom was defined as Engel score of 1A at the last available follow-up. Immediate pre- and post- ablation resting-state functional MRI scans were acquired while maintaining a constant depth of general anesthetic. Multivariable generalized linear models were used to identify intraoperative changes in large-scale connectivity associated with seizure outcomes. RESULTS: Twelve patients underwent MRgLITT for HH, five of whom were seizure-free at their last follow-up. Intraprocedural changes in thalamocortical circuitry involving the anterior cingulate cortex were associated with seizure-freedom. Children who were seizure-free demonstrated an increase and decrease in connectivity to the pregenual and dorsal anterior cingulate cortices, respectively. In addition, children who became seizure-free demonstrated increased thalamic connectivity to the periaqueductal gray immediately following MRgLITT. DISCUSSION: Successful disconnection of HH is associated with intraoperative, large-scale changes in thalamocortical connectivity. These changes provide novel insights into the large-scale basis of gelastic seizures and may represent intraoperative biomarkers of treatment success.

Surgical outcomes in children with drug-resistant epilepsy and hippocampal sclerosis.

BACKGROUND: Hippocampal sclerosis (HS) is a common surgical substrate in adult epilepsy surgery cohorts but variably reported in various pediatric cohorts. OBJECTIVE: We aimed to study the epilepsy phenotype, radiological and pathological variability, seizure and neurocognitive outcomes in children with drug-resistant epilepsy and hippocampal sclerosis (HS) with or without additional subtle signal changes in anterior temporal lobe who underwent surgery. METHODS: This retrospective study enrolled children with drug-resistant focal epilepsy and hippocampal sclerosis with or without additional subtle T2-Fluid Attenuated Inversion Recovery (FLAR)/Proton Density (PD) signal changes in anterior temporal lobe who underwent anterior temporal lobectomy with amygdalohippocampectomy. Their clinical, EEG, neuropsychological, radiological and pathological data were reviewed and summarized. RESULTS: Thirty-six eligible patients were identified. The mean age at seizure onset was 3.7 years; 25% had daily seizures at time of surgery. Isolated HS was noted in 22 (61.1%) cases and additional subtle signal changes in ipsilateral temporal lobe in 14 (38.9%) cases. Compared to the normative population, the group mean performance in intellectual functioning and most auditory and visual memory tasks were significantly lower than the normative sample. The mean age at surgery was 12.3 years; 22 patients (61.1%) had left hemispheric surgeries. ILAE class 1 outcomes was seen in 28 (77.8%) patients after a mean follow up duration of 2.3 years. Hippocampal sclerosis was noted pathologically in 32 (88.9%) cases; type 2 (54.5%) was predominant subtype where further classification was possible. Additional pathological abnormalities were seen in 11 cases (30.6%); these had had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis (63.6% vs 84%, p=0.21). Significant reliable changes were observed across auditory and visual memory tasks at an individual level post surgery. CONCLUSIONS: Favourable seizure outcomes were seen in most children with isolated radiological hippocampal sclerosis. Patients with additional pathological abnormalities had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis.

Stimulation-Induced Seizures in Children Undergoing Stereo-EEG Evaluation.

PURPOSE: This study reports our center's initial experience with the use of low-frequency stimulation in provoking stimulation-induced seizures (SIS) in children with drug-resistant epilepsy undergoing stereo-EEG evaluations. METHODS: This retrospective study enrolled children aged 2 to 18 years with drug-resistant focal epilepsy who underwent stereo-EEG evaluation and extraoperative direct electrical cortical stimulation to elicit seizures. The low-frequency stimulation parameters consisted of biphasic square waveforms at frequency of 1 Hz, pulse width 1 millisecond, current 1 to 3 mA, and train duration of 20 seconds. Various epilepsy-related, imaging, neurophysiology, and surgery-related variables were collected and summarized. RESULTS: Fourteen children (mean age 13 years; 57.1% girls) were included, 10 of whom had unilateral stereo-EEG coverage. Cortical stimulation for provoking seizures was performed after a median of 5 days after electrode implantation. The median number of electrode-contacts stimulated per patient was 42. Four patients (28.6%) experienced habitual SIS (all extratemporal). The etiology in three patients was focal cortical dysplasia. Interictal high-frequency oscillations at electrode-contacts provoking SIS were observed in three cases (75%). Two of these individuals (50%) had class 1 International League Against Epilepsy seizure outcome at last follow-up, after the resection of the brain regions generating SIS. CONCLUSIONS: Low-frequency (1-Hz) stimulation could provoke habitual SIS in nearly one-fourth of children with focal epilepsy undergoing stereo-EEG monitoring. This study provides a limited pediatric experience with the low-frequency cortical stimulation and SIS.

Drug-resistant focal epilepsy in a girl with SETD5-related intellectual disability.

None.

Contralateral hippocampal sclerosis following functional hemispherectomy in children: A report of three cases.

PURPOSE: Hippocampal Sclerosis (HS) may co-exist with temporal or extratemporal lesions (dual pathology) in children and is usually ipsilateral to the radiological lesion. Here were report three cases with extensive hemispheric cortical malformation and drug resistant epilepsy who had persistent seizures after functional hemispherectomy (FH) and developed contralateral HS after the surgery. METHODS: This retrospective study enrolled children who underwent FH and developed contralateral HS after surgery. Their clinical, EEG, radiological and pathological data were reviewed and summarized. RESULTS: Ninety-five children underwent FH during the study period; Three cases (3.2%) were eligible. They all had unilateral extensive hemispheric cortical malformation who underwent FH between 3 and 5 months of age with no clinical, EEG or radiological suggestion for involvement of contralateral hemisphere prior to FH. All three patients had persisting seizures after FH. Contralateral HS was detected between 2.2 to 3.7 years after FH in all three cases. Two of the patients showed pathogenic variants in GATOR1 pathway genes. CONCLUSIONS: The genesis of contralateral HS in the reported patients remains unexplained. The presence and distribution of "second-hit" somatic mutations may play an important role in governing the seizure outcomes of epilepsy surgery in patients with apparently unilateral malformations of cortical development.

Epilepsy surgery outcomes in patients with GATOR1 gene complex variants: Report of new cases and review of literature.

AIM: To report seizure outcomes in children with GATOR1 gene complex disorders who underwent epilepsy surgery and perform a systematic literature search to study the available evidence. METHODS: The records of children with pathogenic/likely pathogenic variants in GATOR1 gene complex who underwent epilepsy surgery were reviewed. Clinical, radiological, neurophysiological, and histological data were extracted/summarized. The systematic review included all case series/reports and observational studies reporting on children or adults with genetic (germline or somatic) variants in the GATOR1 complex genes (DEPDC5, NPRL2, NPRL3) with focal epilepsy with/without focal cortical dysplasia who underwent epilepsy surgery; seizure outcomes were analyzed. RESULTS: Eight children with pathogenic/likely pathogenic variants in GATOR1 complex genes were included. All had drug-resistant epilepsy. Six children had significant neurodevelopmental delay. Epilepsy surgery was performed in all; clinical seizure freedom was noted in 4 children (50%). Systematic literature search identified 17 eligible articles; additional 30 cases with patient-level data were studied. Lesional MRI brain was seen in 80% cases. The pooled rate of seizure freedom following surgery was 60%; FCD IIa was the most encountered pathology. INTERPRETATION: Epilepsy surgery may be effective in some children with GATOR1 complex gene variants. Seizure outcomes may be compromised by extensive epileptogenic zones.

Comparing late-onset epileptic spasm outcomes after corpus callosotomy and subsequent disconnection surgery between post-encephalitis/encephalopathy and non-encephalitis/encephalopathy.

OBJECTIVE: We aimed to analyze the efficiency of corpus callosotomy (CC) and subsequent disconnection surgeries in patients with late-onset epileptic spasms (LOES) by comparing post-encephalitis/encephalopathy (PE) and non-encephalitis/encephalopathy (NE). We hypothesized these surgeries can control potential focal onset epileptic spasms (ES) in the NE group but not in the PE group. METHODS: We retrospectively included 23 patients (12 with PE and 11 with NE) who initially underwent CC and subsequent disconnection surgeries (five NE). We compared the clinical courses, seizure types, MRI, video-EEG, epilepsy surgery, and seizure outcomes between the two groups. RESULTS: The median age of LOES onset in the PE group was 2.8 (range 1.0-10.1 years) and 2.9 years (range 1.1-12.6) in the NE group. Bilateral MRI abnormalities were observed in both groups (PE, n = 12; NE, n = 3; P < 0.05). The PE group presented ES alone (n = 2), ES + focal seizures (FS) (n = 3), ES + generalized seizures (GS) (n = 3), and ES + FS + GS (n = 4) in addition to stimulus-induced startle seizures (SS) (n = 8) (mean 3.1 seizure types/patient). The NE group presented ES alone (n = 1), ES + FS (n = 2), and ES + FS + GS (n = 8) (mean 2.7 seizure types/patient). In the PE group, CC stopped ES (n = 1) and SS (n = 1) and achieved <50% SS (n = 3). In the NE group, CC achieved immediate ES-free status (n = 2) and < 50% ES (n = 1), and additional disconnection surgeries subsided all seizure types (n = 3) based on lateralized interictal/ictal EEG findings. LOES was significantly remitted by surgery in the NE group (6/11 [55%]) compared with the PE group (1/12 [8%]) (P < 0.05). SIGNIFICANCE: LOES is a drug-resistant, focal/generalized/unknown onset ES. Lateralization of ES in NE could be achieved after CC and eliminated by further disconnection surgeries because of potential focal onset ES. LOES in PE had little benefit from CC for generalized onset ES. However, CC might reduce SS in patients in the PE group with multiple seizure types.

Connectomic Profiles and Cognitive Trajectories After Epilepsy Surgery in Children.

BACKGROUND AND OBJECTIVES: Neurocognitive outcomes after surgery for temporal lobe epilepsy in childhood are variable. Postoperative changes are not directly predicted by seizure freedom, and associations between epilepsy, neuropsychological function, and developing neural networks are poorly understood. Here, we leveraged whole-brain connectomic profiling in magnetoencephalography (MEG) to retrospectively study associations between brain connectivity and neuropsychological function in children with temporal lobe epilepsy undergoing resective surgery. METHODS: Clinical and MEG data were retrospectively analyzed for children who underwent temporal lobe epilepsy surgery at the Hospital for Sick Children from 2000 to 2021. Resting-state connectomes were constructed from neuromagnetic oscillations via the weighted-phase lag index. Using a partial least-squares (PLS) approach, we assessed multidimensional associations between patient connectomes, neuropsychological scores, and clinical covariates. Bootstrap resampling statistics were performed to assess statistical significance. RESULTS: A total of 133 medical records were reviewed, and 5 PLS analyses were performed. Each PLS analysis probed a particular neuropsychological domain and the associations between its baseline and postoperative scores and the connectomic data. In each PLS analysis, a significant latent variable was identified, representing a specific percentage of the variance in the data and relating neural networks to clinical covariates, which included changes in rote verbal memory (n = 41, p = 0.01, σ2 = 0.38), narrative/verbal memory (n = 57, p = 0.00, σ2 = 0.52), visual memory (n = 51, p = 0.00, σ2 = 0.43), working memory (n = 44, p = 0.00, σ2 = 0.52), and overall intellectual function (n = 59, p = 0.00, σ2 = 0.55). Children with more diffuse, bilateral intrinsic connectivity across several frequency bands showed lower scores on all neuropsychological assessments but demonstrated a greater propensity for gains after resective surgery. DISCUSSION: Here, we report that connectomes characterized by diffuse connectivity, reminiscent of developmentally immature networks, are associated with lower preoperative cognition and postoperative cognitive improvement. These findings provide a potential means to understand neurocognitive function in children with temporal lobe epilepsy and expected changes postoperatively.

Delineation of the epileptogenic zone by Phase-amplitude coupling in patients with Bottom of Sulcus Dysplasia.

PURPOSE: The removal of the bottom of sulcus dysplasia (BOSD) often includes the gyral crown; however, this method has been controversial. We hypothesized that the epileptogenic zone of the BOSD does not include the gyral crown. To reveal the depth and extent of the epileptogenic zone of the BOSD, we applied the two electrophysiological modalities: (1) the occurrence rate (OR) of high-frequency oscillations (HFOs) and (2) modulation index (MI), reflecting the strength of phase-amplitude coupling between HFOs and slow oscillations. METHODS: We investigated the ripples [80-200 Hz] and fast ripples [200-300 Hz]) in HFOs and MI (HFOs [80-300 Hz] and slow oscillations [3-4 Hz]). We opened the sulcus at the BOSD and implanted the subdural electrodes directly over the MRI visible lesion. All patients (n = 3) underwent lesionectomy and the gyral crown was preserved. RESULTS: Pathological findings demonstrated focal cortical dysplasia type IIb and seizure freedom was achieved. The OR of the HFOs was not significantly different between the BOSD and the gyral crown. In contrast, the MI between HFOs and slow oscillations in the BOSD was significantly higher than that in the gyral crown. CONCLUSION: High MI values distinguished the epileptogenic BOSD from the non-epileptogenic gyral crowns. MI could be a more informative biomarker of epileptogenicity than the OR of HFOs in a subset of patients with the BOSD.

Current Status and Future Objectives of Surgical Therapies for Epilepsy in Japan.

This study investigated the number of epilepsy surgeries performed over time in Japan, and conducted a questionnaire survey of the Japan Neurosurgical Society (JNS) training program core hospitals to determine the current status and future objectives of surgical therapies and epilepsy training programs for physicians in Japan. This article presents part of a presentation delivered as a presidential address at the 44th Annual Meeting of the Epilepsy Surgery Society of Japan held in January 2021. The number of epilepsy surgeries performed per year has increased in Japan since 2011 to around 1,200 annually between 2015 and 2018. The questionnaire survey showed that 50% of the responding hospitals performed epilepsy surgery and 29% had an epilepsy center, and that these hospitals provided senior residents with education regarding epilepsy surgery. The presence of an epilepsy center in a hospital was positively correlated with the availability of long-term video electroencephalography monitoring beds as well as the number of epilepsy surgeries performed at the hospital. In regions with no medical facilities offering specialized surgical therapies for epilepsy, the JNS training program core hospitals may help improve epilepsy diagnosis and treatment. They may also increase the number of safe and effective surgeries by establishing epilepsy centers that can perform long-term video electroencephalography monitoring, providing junior neurosurgeons with training regarding epilepsy, and playing a core role in surgical therapies for epilepsy in tertiary medical areas in close cooperation with neighboring medical facilities.

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.

Case Report: Subtotal Hemispherotomy Modulates the Epileptic Spasms in Aicardi Syndrome.

The mechanism of epileptic spasms (ES) in Aicardi syndrome (AS) remains obscure. We compared intraoperative high-frequency oscillations (HFOs) and phase-amplitude coupling (PAC) before and after subtotal hemispherotomy in a 3-month-old girl with drug-resistant ES secondary to AS. Fetal ultrasonography showing corpus callosum agenesis, bilateral ventricular dilatation, and a large choroid plexus cyst confirmed AS diagnosis. Her ES started when she was 1 month old and had ten series of clustered ES per day despite phenobarbital and vitamin B6 treatment. After subtotal hemispherotomy, her ES dramatically improved. We analyzed two intraoperative electrocorticography modalities: (1), occurrence rate (OR) of HFOs; (2), PAC of HFOs and slow wave bands in the frontal, central, and parietal areas. We hypothesized that HFOs and PAC could be the biomarkers for efficacy of subtotal hemispherotomy in AS with ES. PAC in all three areas and OR of HFOs in the frontal and parietal areas significantly decreased, while OR of HFOs in the central area remained unchanged after subtotal hemispherotomy. We have demonstrated the usefulness of evaluating intraoperative HFOs and PAC to assess subtotal hemispherotomy effectiveness in AS patients with ES. Disconnecting the thalamocortical and subcortical pathways in the epileptic network plays a role in controlling ES generation.

Surgical outcomes in children with bottom-of-sulcus dysplasia and drug-resistant epilepsy: a retrospective cohort study.

OBJECTIVE: Bottom-of-sulcus dysplasia (BOSD) is challenging to identify radiologically. The aim of this study was to explore seizure outcomes after resective surgery or MR-guided laser interstitial thermal therapy (MRgLITT) in children with BOSD. METHODS: Children with radiologically defined BOSD who underwent resective surgery or MRgLITT, with at least 1 year of follow-up were included. Clinical, radiological, neurophysiological, and histological data were extracted from medical records. Invasive video EEG (IVEEG) was used to evaluate the ictal onset zone or motor/language mapping, wherever appropriate. Histology of MRI-visible BOSD, including the overlying and adjacent cortex, was also evaluated. RESULTS: Forty-one children with BOSD underwent surgical treatment. The lesion was initially overlooked on MRI in 20 patients (48.8%). Of 34 patients who underwent IVEEG and who had available ictal data, the ictal onset zone extended beyond the MRI-visible BOSD in 23 patients (67.6%). Surgical treatment included lesionectomy (24 patients), extended lesionectomy (12 patients), lobectomy (1 patient), and ablation of BOSD (4 patients). The pathology in 37 patients who underwent resection showed focal cortical dysplasia type IIB and type IIA in 21 (53.8%) and 16 patients (41%), respectively. Seizure freedom was achieved in 32 patients (78.1%) after a mean follow-up of 4.3 years. CONCLUSIONS: Seizure outcomes after resective surgery or MRgLITT in children with BOSD were generally favorable. The authors found that the neurophysiological abnormality and pathology often extended beyond the MRI-visible BOSD.

A review of magnetoencephalography use in pediatric epilepsy: an update on best practice.

Introduction: Magnetoencephalography (MEG) is a noninvasive technique that is used for presurgical evaluation of children with drug-resistant epilepsy (DRE).Areas covered: The contributions of MEG for localizing the epileptogenic zone are discussed, in particular in extra-temporal lobe epilepsy and focal cortical dysplasia, which are common in children, as well as in difficult to localize epilepsy such as operculo-insular epilepsy. Further, the authors review current evidence on MEG for mapping eloquent cortex, its performance, application in clinical practice, and potential challenges.Expert opinion: MEG could change the clinical management of children with DRE by directing placement of intracranial electrodes thereby enhancing their yield. With improved identification of a circumscribed epileptogenic zone, MEG could render more patients as suitable candidates for epilepsy surgery and increase utilization of surgery.

Distinct dual cortico-cortical networks successfully identified between supplemental and primary motor areas during intracranial EEG for drug-resistant frontal lobe epilepsy.

We present a case of drug-resistant focal motor seizures in which separate cortico-cortical epileptic networks within the supplementary motor area (SMA) proper and primary motor area (PMA) were proven by ictal high-frequency oscillation (HFO) and cortico-cortical evoked potential (CCEP). A 12-year-old girl presented with two types seizures: type A, tonic extension and subsequent clonic movements of the right arm; and type B, tonic and clonic movements of the right leg. MRI was normal and karyotype genetic analysis revealed 46,X,t(X;14)(q13;p12). She underwent placement of chronic subdural electrodes over the left hemisphere. We recorded a total of nine seizures during 10 days of epilepsy monitoring. Type A seizures started from the lower part of the left SMA proper and early spread to the hand motor area of the PMA. Type B seizures started from the upper part of the SMA proper and early spread to the leg motor area of the PMA. CCEPs of both SMA proper and PMA activated two identical routes for evoked potentials correlating with separate pathways. Corticectomy of the left SMA proper and PMA achieved seizure-free without hemiparesis. Within a small homunculus of the SMA proper, separate epileptic networks were proven and validated by seizure semiology, ictal HFO, and CCEP.

Supplementing Extraoperative Electrocorticography With Real-Time Intraoperative Recordings Using the Same Chronically Implanted Electrodes.

BACKGROUND: The practice of intraoperative electrocorticography (iECoG) to guide resective epilepsy surgery is variable. Limitations of iECoG include variability in recordings from previously unsampled cortex, increased operative time and cost, and a lack of clear benefit to surgical decision-making. OBJECTIVE: To describe a simple technique to supplement extraoperative intracranial recordings with real-time iECoG using the same chronically implanted electrodes that overcome some of these limitations. METHODS: We describe the technical procedure, intraoperative findings, and outcomes of 7 consecutive children undergoing 2-stage resective epilepsy surgery with invasive subdural grid monitoring between January 2017 and December 2019. All children underwent placement of subdural grids, strips, and depth electrodes. Planned neocortical resection was based on extraoperative mapping of ictal and interictal recordings. During resection in the second stage, the same electrodes were used to perform real-time iECoG. RESULTS: Real-time iECoG using this technique leads to modification of resection for 2 of the 7 children. The first was extended due to an electroencephalographic seizure from a distant electrode not part of the original resection plan. The second was restricted due to attenuation of epileptiform activity following a partial resection, thereby limiting the extent of a Rolandic resection. No infections or other adverse events were encountered. CONCLUSION: We report a simple technique to leverage chronically implanted electrodes for real-time iECoG during 2-stage resective surgery. This technique presents fewer limitations than traditional approaches and may alter intraoperative decision-making.

Phase-amplitude coupling of interictal fast activities modulated by slow waves on scalp EEG and its correlation with seizure outcomes of disconnection surgery in children with intractable nonlesional epileptic spasms.

OBJECTIVE: Epileptic spasms (ESs) are classified as focal, generalized, or unknown onset ESs. The classification of ESs and surgery in patients without lesions apparent on MRI is challenging. Total corpus callosotomy (TCC) is a surgical option for diagnosis of the lateralization and possible treatment for ESs. This study investigated phase-amplitude coupling (PAC) of fast activity modulated by slow waves on scalp electroencephalography (EEG) to evaluate the strength of the modulation index (MI) before and after disconnection surgery in children with intractable nonlesional ESs. The authors hypothesize that a decreased MI due to surgery correlates with good seizure outcomes. METHODS: The authors studied 10 children with ESs without lesions on MRI who underwent disconnection surgeries. Scalp EEG was obtained before and after surgery. The authors collected 20 epochs of 3 minutes each during non-rapid eye movement sleep. The MI of the gamma (30-70 Hz) amplitude and delta (0.5-4 Hz) phase was obtained in each electrode. MIs for each electrode were averaged in 4 brain areas (left/right, anterior/posterior quadrants) and evaluated to determine the correlation with seizure outcomes. RESULTS: The median age at first surgery was 2.3 years (range 10 months-9.1 years). Two patients with focal onset ESs underwent anterior quadrant disconnection (AQD). TCC alone was performed in 5 patients with generalized or unknown onset ESs. Two patients achieved seizure freedom. Three patients had residual generalized onset ESs. Disconnection surgeries in addition to TCC consisted of TCC + posterior quadrant disconnection (PQD) (1 patient); TCC + AQD + PQD (1 patient); and TCC + AQD + hemispherotomy (1 patient). Seven patients became seizure free with a mean follow-up period of 28 months (range 5-54 months). After TCC, MIs in 4 quadrants were significantly lower in the 2 seizure-free patients than in the 6 patients with residual ESs (p < 0.001). After all 15 disconnection surgeries in 10 patients, MIs in the 13 target quadrants for each disconnection surgery that resulted in freedom from seizures were significantly lower than in the 26 target quadrants in patients with residual ESs (p < 0.001). CONCLUSIONS: In children with nonlesional ESs, PAC for scalp EEG before and after disconnection surgery may be a surrogate marker for control of ESs. The MI may indicate epileptogenic neuronal modulation of the interhemispheric corpus callosum and intrahemispheric subcortical network for ESs. TCC may be a therapeutic option to disconnect the interhemispheric modulation of epileptic networks.

Relapse of Herpes Simplex Encephalitis by Epilepsy Surgery 35 Years after the First Infection: A Case Report and Literature Review.

Late relapse of herpes simplex encephalitis (HSE) is defined as the recurrence of HSE more than 3 months after the initial exposure. The postoperative diagnosis of HSE following neurosurgery is complicated because the clinical presentation can mimic other common complications of neurosurgery. Cerebrospinal fluid polymerase chain reactions (CSF-PCR) is the gold standard for the diagnosis of HSE. We describe a case of late HSE relapse after epilepsy surgery in a patient who required a brain biopsy due to repeated negative CSF-PCR results. A 38-year-old woman had a history of HSE from the age of 3 years. She had intractable epilepsy from the age of 20 years and underwent right posterior quadrant disconnection (PQD) at the age of 38 years. Postoperatively, she had a right hemispheric intracerebral hemorrhage (ICH) and her consciousness was gradually worsening. Her consciousness improved after removal of the ICH. However, her consciousness gradually deteriorated again. Fluid-attenuated inversion recovery (FLAIR) revealed bilateral hyperintensity in the frontal lobes, including the white matter. CSF-PCR for herpes simplex virus (HSV) was performed twice, but yielded negative results. We performed a brain biopsy to target FLAIR hyperintensity in the right frontal lobe. PCR of the brain specimen was positive for HSV. Her consciousness improved with acyclovir, methylprednisolone, and cyclophosphamide. To our knowledge, this is a case of HSE induced by epilepsy surgery which had the longest duration until relapse after the initial HSE episode. A brain biopsy can be used to confirm the diagnosis of suspected HSE when CSF-PCR results are negative.

Brainstem Associated Somatosensory Evoked Potentials and Response to Vagus Nerve Stimulation: An Investigation of the Vagus Afferent Network.

Despite decades of clinical usage, selection of patients with drug resistant epilepsy who are most likely to benefit from vagus nerve stimulation (VNS) remains a challenge. The mechanism of action of VNS is dependent upon afferent brainstem circuitry, which comprises a critical component of the Vagus Afferent Network (VagAN). To evaluate the association between brainstem afferent circuitry and seizure response, we retrospectively collected intraoperative data from sub-cortical recordings of somatosensory evoked potentials (SSEP) in 7 children with focal drug resistant epilepsy who had failed epilepsy surgery and subsequently underwent VNS. Using multivariate linear regression, we demonstrate a robust negative association between SSEP amplitude (p < 0.01), and seizure reduction. There was no association between SSEP latency and seizure outcomes. Our findings provide novel insights into the mechanism of VNS and inform our understanding of the importance of brainstem afferent circuitry within the VagAN for seizure responsiveness following VNS.

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.