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Introduction: In carefully selected patients with medically refractory epilepsy, disconnective hemispherotomy can result in significant seizure freedom; however, incomplete disconnection can result in ongoing seizures and poses a significant challenge. Completion hemispherotomy provides an opportunity to finish the disconnection. We describe the use of magnetic resonance-guided laser interstitial thermal ablation (MRgLITT) for completion hemispherotomy. Methods: Patients treated with completion hemispherotomy using MRgLITT at our institution were identified. Procedural and seizure outcomes were evaluated retrospectively. Results: Five patients (3 males) underwent six MRgLITT procedures (one child treated twice) for completion hemispherotomy at a median age of 6 years (range 1.8–12.9). Two children had hemimegalencephaly, two had Rasmussen encephalitis, and one had polymicrogyria. All five children had persistent seizures likely secondary to incomplete disconnection after their functional hemispherotomy. The mean time from open hemispherotomy to MRgLITT was 569.5 ± 272.4 days (median 424, range 342–1,095). One patient underwent stereoelectroencephalography before MRgLITT. The mean number of ablation targets was 2.3 ± 0.47 (median 2, range 2–3). The mean length of the procedure was 373 min ± 68.9 (median 374, range 246–475). Four of the five patients were afforded improvement in their neurocognitive functioning and speech performance after ablation, with mean daily seizure frequency at 1 year of 1.03 ± 1.98 (median 0, range 0–5). Two patients achieved Engel Class I outcomes at 1 year after ablation, one was Engel Class III, and two were Engel Class IV. The mean follow-up time was 646.8 ± 179.5 days (median 634, range 384–918). No MRgLITT-related complications occurred. Delayed retreatment (>1 year) occurred in three patients: one child underwent redo ablation and two underwent anatomic hemispherectomy. Conclusion: We have demonstrated the feasibility of a minimally invasive approach for completion hemispherotomy using MRgLITT. Delayed retreatment was needed in three patients; thus, further study of this technique with comparison to other surgical techniques is warranted.

To date, more than 100 clinical trials have used sequence-based therapies to address diseases of the pediatric central nervous system. The first targeted pathologies share common features: the diseases are severe; they are due (mostly) to single variants; the variants are well characterized within the genome; and the interventions are technically feasible. Interventions range from intramuscular and intravenous injection to intrathecal and intraparenchymal infusions. Whether the therapeutic sequence consists of RNA or DNA, and whether the sequence is delivered via simple oligonucleotide, nanoparticle, or viral vector depends on the disease and the involved cell type(s) of the nervous system. While only one active trial targets an epilepsy disorder—Dravet syndrome—experiences with aromatic L-amino acid decarboxylase deficiency, spinal muscular atrophy, and others have taught us several lessons that will undoubtedly apply to the future of gene therapy for epilepsies. Epilepsies, with their diverse underlying mechanisms, will have unique aspects that may influence gene therapy strategies, such as targeting the epileptic zone or nodes in affected circuits, or alternatively finding ways to target nearly every neuron in the brain. This article focuses on the current state of gene therapy and includes its history and premise, the strategy and delivery vehicles most commonly used, and details viral vectors, current trials, and considerations for the future of pediatric intracranial gene therapy.

The field of minimally invasive surgery has evolved over the past 50 years, including neurosurgery, with an evolution to “minimally invasive neurosurgery” when feasible. Epilepsy surgery has followed this trend, with a transition from standard neurosurgical techniques to minimally invasive techniques in all phases of neurosurgical involvement. These include the diagnostic intracranial electroencephalogram with a subdural exploration to stereoelectroencephalography, the actual resection from an open craniotomy to a less destructive technique, or the multiple modalities of neuromodulation instead of a destructive surgery.The influence of these minimally invasive techniques has resulted in a change in the overall philosophy of pediatric epilepsy surgery. The expectations of what is considered “successful” epilepsy surgery has changed from total seizure control, in other words, a “cure,” to palliative epilepsy surgery with a decrease in the targeted seizures, especially “disabling seizures.” This has led to an overall greater acceptance of epilepsy surgery. This article summarizes the major reasons behind the explosion of minimally invasive pediatric epilepsy surgery, which are amplified in the subsequent articles. Some of this chapter includes the authors' opinions.

Introduction: Vagus nerve stimulation (VNS) is an adjunctive treatment in children with intractable epilepsy. When lead replacement becomes necessary, the old leads are often truncated and retained and new leads are implanted at a newly exposed segment of the nerve. Direct lead removal and replacement is infrequently described, with outcomes poorly characterized. We aimed to describe our experience with feasibility of VNS lead removal and replacement in pediatric patients. Methods: Retrospective review examined 14 patients, at a single, tertiary-care, children’s hospital, who underwent surgery to replace VNS leads, with complete removal of the existing lead from the vagus nerve and placement of a new lead on the same segment of the vagus nerve, via blunt and sharp dissection without use of electrocautery. Preoperative characteristics, stimulation parameters, and outcomes were collected. Results: Mean age at initial VNS placement was 7.6 years (SD 3.5, range 4.5-13.4). Most common etiologies of epilepsy were genetic (5, 36%) and cryptogenic (4, 29%). Lead replacement was performed at a mean of 6.0 years (SD 3.8, range 2.1-11.7) following initial VNS placement. Reasons for revision included VNS lead breakage or malfunction. There were no perioperative complications, including surgical site infection, voice changes, dysphagia, or new deficits postoperatively. Stimulation parameters after replacement surgery at last follow-up were similar compared to preoperatively, with final stimulation parameters ranging from 0.25 mA higher to 1.5 mA lower to maintain baseline seizure control. Mean length of follow-up was 7.9 years (SD 3.5, range 3.1-13.7).Conclusion: Removal and replacement of VNS leads is feasible and can be safely performed in children. Further characterization of surgical technique, associated risk, impact on stimulation parameters, and long-term outcomes are needed to inform best practices in VNS revision.

OBJECTIVE Periventricular nodular heterotopia (PVNH) is a result of disrupted neuronal migration from the ventricular system and can be a rare cause of refractory focal epilepsy. The goal of this case series was to describe the treatment of pediatric PVNH-related epilepsy with MR-guided laser interstitial thermal ablation. METHODS Patients treated at a single institution with MR-guided laser interstitial thermal therapy (MRgLITT) for PVNH-related epilepsy were identified. Preoperative and postoperative seizure outcomes and procedural information were evaluated. RESULTS Five children with PVNH treated with MRgLITT were reviewed; 1 child was treated twice. Three patients were female; the median age was 10.9 years. Five of 6 treatments were preceded by stereoelectroencephalography phase II monitoring. Three children experienced unilateral PVNH, and 2 had bilateral seizures. The median number of seizures recorded during phase II monitoring was 2; the median number of ablation targets was 2 (range 1–4). All patients experienced a decrease in seizure frequency; 4 patients (80%) had an Engel class ≤ III at the last follow-up (range I–IV). One child experienced right hemianopia posttreatment. CONCLUSIONS This case series investigation has illustrated a novel, minimally invasive approach for treating pediatric PVNH-related epilepsy. Further study of this technique with comparison with other surgical techniques is warranted.

Ependymomas comprise approximately 10 percent of childhood CNS malignancies and are associated with dismal outcomes if metastatic, incompletely resected, or recurrent.1 Standard therapy consists of maximal safe surgical resection followed by focal irradiation.2 Recurrent fusion genes involving C11orf95-RELA or YAP1 have been identified in supratentorial ependymomas, but targetable molecular lesions are rare.3,4 Here, we report a sustained response to larotrectinib in a pediatric patient with a histologic diagnosis of recurrent metastatic anaplastic ependymoma, whose molecular testing unexpectedly revealed a KANK1-NTRK2 fusion and methylation profile most consistent with pleomorphic xanthoastrocytoma (PXA). This case highlights the potentially profound clinical implications of integrating genomic profiling into the diagnostic evaluation of pediatric CNS tumors.

OBJECTIVE Several small series have described stereotactic MRI-guided laser interstitial thermal therapy for partial callosotomy of astatic and generalized tonic-clonic (GTC) seizures, especially in association with Lennox-Gastaut syndrome. Larger case series and comparison of distinct stereotactic methods for stereotactic laser corpus callosotomy (SLCC), however, are currently lacking. The objective of this study was to report seizure outcomes in a series of adult patients with epilepsy following anterior, posterior, and complete SLCC procedures and to compare the results achieved with a frameless stereotactic surgical robot versus direct MRI guidance frames. METHODS The authors retrospectively reviewed sequential adult epilepsy surgery patients who underwent SLCC procedures at a single institution. They describe workflows, stereotactic errors, percentage disconnection, hospitalization durations, adverse events, and seizure outcomes after performing anterior, posterior, and complete SLCC procedures using a frameless stereotactic surgical robot versus direct MRI guidance platforms. RESULTS Thirteen patients underwent 15 SLCC procedures. The median age at surgery was 29 years (range 20–49 years), the median duration of epilepsy was 21 years (range 9–48 years), and median postablation follow-up was 20 months (range 4–44 months). Ten patients underwent anterior SLCC with a median 73% (range 33%–80%) midsagittal length of callosum acutely ablated. Following anterior SLCC, 6 of 10 patients achieved meaningful (> 50%) reduction of target seizures. Four patients underwent posterior (completion) SLCC following prior anterior callosotomy, and 1 patient underwent complete SLCC as a single procedure; 3 of these 5 patients experienced meaningful reduction of target seizures. Overall, 8 of 10 patients in whom astatic seizures were targeted and treated by anterior and/or posterior SLCC experienced meaningful improvement. SLCC procedures with direct MRI guidance (n = 7) versus a frameless surgical robot (n = 8) yielded median radial accuracies of 1.1 mm (range 0.2–2.0 mm) versus 2.4 mm (range 0.6–6.1 mm; p = 0.0011). The most serious adverse event was a clinically significant intraparenchymal hemorrhage in a patient who underwent the robotic technique. CONCLUSIONS This is the largest reported series of SLCC for epilepsy to date. SLCC provides seizure outcomes comparable to open surgery outcomes reported in the literature. Direct MRI guidance is more accurate, which has the potential to reduce the risks of SLCC. Methodological advancements and larger studies are needed.

Zusammenfassung Einleitung Die stereotaktische Laserthermoablation (SLTA) stellt eine minimal-invasive Behandlung für therapierefraktäre Epilepsien auf dem Boden eines hypothalamischen Hamartoms (HH) dar. Durch die weitreichenden Folgen einer therapierefraktären Epilepsie können hohe direkte Kosten entstehen, die durch eine zu erzielende Anfallsfreiheit gesenkt werden können. Methoden Anhand einer Patientin mit einem HH sollen die Auswirkungen einer solchen Erkrankung beleuchtet und der Krankheitsverlauf nach erfolgter SLTA dargestellt werden. Zur Beurteilung der Kosteneffizienz der SLTA wurden die direkten Kosten, basierend auf den Krankenversicherungsdaten der Patientin, über die Versicherungsjahre 2017 bis 2020 analysiert. Ergebnisse Bei der Patientin bestand eine hochaktive, medikamentenrefraktäre Epilepsie mit erhöhtem Verletzungsrisiko und zunehmender Verschlechterung der schulischen Leistung und der psychischen Verfassung. Begleitend bestand durch das HH eine Pubertas praecox. Nach SLTA entwickelte die Patientin mit einem Follow-up von 26 Monaten eine vollständige Anfallsfreiheit sowie eine endokrinologische Stabilisierung, sodass die antikonvulsive als auch die hormonelle Medikation im Verlauf beendet werden konnten. Relevante persistierende Komplikationen wurden nicht beobachtet. Die direkten jährlichen Kosten (stationär [ausschließlich der SLTA selbst]/ambulant/Medikamente) reduzierten sich von € 6603 in 2017 und € 12.903 in 2018 auf € 3609 in 2019 und zuletzt € 617 in 2020, was einer Reduktion von bis zu 95 % (2018 gegenüber 2020) entsprach. Zusätzlich konnten die Kosten einer geplanten Integrationsassistenz von schätzungsweise € 18.000/Jahr eingespart werden. Schlussfolgerung Die SLTA stellt eine effektive und risikoarme Behandlung von HH dar und führt bereits nach 2 Jahren zu einer relevanten Einsparung der direkten Kosten, was bei der Kosten-Nutzen-Abwägung der SLTA einzubeziehen ist.

Introduction: Hypothalamic hamartoma is rarely associated with epileptic spasms. We describe epileptic spasms in a large cohort of hypothalamic hamartoma patients. Methods: We performed a retrospective chart review between March 2011 and March 2020 to identify patients with hypothalamic hamartoma and epilepsy. Results: We identified 114 patients with hypothalamic hamartoma and epilepsy, only 3 male patients (2.6%) also had epileptic spasms. The epileptic spasms developed between 6 and 18 months of age. Epileptic spasms resolved with oral prednisolone in 1 and with vigabatrin in the second patient. The third patient continued epileptic spasms despite multiple antiepileptic drugs and partial resection of hypothalamic hamartoma. All 3 patients underwent laser-ablation of hypothalamic hamartoma at the age of 14, 29, and 63 months. The seizure burden decreased by 100%, 84%, and 93% at follow-up (3-47 months). Conclusions: Epileptic spasms are rare in hypothalamic hamartoma patients and early laser-ablation could potentially treat epileptic spasms and all other seizure types associated with hypothalamic hamartoma.

Epilepsy occurs in nearly all patients with tuberous sclerosis and is often refractory to medical treatment. The definition of surgical candidacy in these patients has broadened in recent years due to philosophical and technological advances. The goals of surgery have shifted to focusing on quality of life and maximizing neurodevelopmental potential in patients unable to obtain seizure freedom. Novel diagnostic, ablative, and neuromodulatory techniques have been developed that may help patients that were previously considered inoperable to have an improved quality of life. In the coming years, it is expected that these techniques will be further refined and lead to an improvement of neurological prognosis in patients with tuberous sclerosis.

This article overviews the surgical options for hypertonia management in cerebral palsy, both spasticity and dystonia. We review the history and use of intrathecal baclofen. We contrast its use with the indications for selective dorsal rhizotomy and review how it is the optimal technique to lower tone in the ambulatory spastic diplegic patient with cerebral palsy. This article reviews the advent of deep brain stimulation, with an emphasis on selection criteria and expected outcomes in this population. The article reviews the principles and use of selective peripheral neurotomy as it is applied to focal spasticity not requiring systemic tone reduction.

Background and Purpose The current tools available for localization of expressive language, including functional magnetic resonance imaging (fMRI) and cortical stimulation mapping (CSM), require that the patient remain stationary and follow language commands with precise timing. Many pediatric epilepsy patients, however, have intact language skills but are unable to participate in these tasks due to cognitive impairments or young age. In adult subjects, there is evidence that language laterality can be determined by resting state (RS) fMRI activity, however there are few studies on the use of RS to accurately predict language laterality in children. Methods A retrospective review of pediatric patients at Texas Children's Hospital was performed to identify patients who have undergone epilepsy surgical planning over 3 years with language localization using traditional methods of Wada testing, CSM, or task-based fMRI with calculated laterality index, as well as a 7-minute RS scan available without excessive motion or noise. We found the correlation between each subject's left and right Broca's region activity and each of 68 cortical regions. Results A group of nine patients with left-lateralized language were found to have greater voxel-wise correlations than a group of six patients with right-lateralized language between a left hemispheric Broca's region seed and the following six cortical regions: left inferior temporal, left lateral orbitofrontal, left pars triangularis, right lateral orbitofrontal, right pars orbitalis and right superior frontal regions. Conclusions In a cohort of children with epilepsy, we found that patients with left- and right-hemispheric language lateralization have different RS networks.

Objective. High-frequency oscillations (HFOs) are considered a biomarker of the epileptogenic zone in intracranial EEG recordings. However, automated HFO detectors confound true oscillations with spurious events caused by the presence of artifacts. Approach. We hypothesized that, unlike pseudo-HFOs with sharp transients or arbitrary shapes, real HFOs have a signal characteristic that can be represented using a small number of oscillatory bases. Based on this hypothesis using a sparse representation framework, this study introduces a new classification approach to distinguish true HFOs from the pseudo-events that mislead seizure onset zone (SOZ) localization. Moreover, we further classified the HFOs into ripples and fast ripples by introducing an adaptive reconstruction scheme using sparse representation. By visualizing the raw waveforms and time-frequency representation of events recorded from 16 patients, three experts labeled 6400 candidate events that passed an initial amplitude-threshold-based HFO detector. We formed a redundant analytical multiscale dictionary built from smooth oscillatory Gabor atoms and represented each event with orthogonal matching pursuit by using a small number of dictionary elements. We used the approximation error and residual signal at each iteration to extract features that can distinguish the HFOs from any type of artifact regardless of their corresponding source. We validated our model on sixteen subjects with thirty minutes of continuous interictal intracranial EEG recording from each. Main results. We showed that the accuracy of SOZ detection after applying our method was significantly improved. In particular, we achieved a 96.65% classification accuracy in labeled events and a 17.57% improvement in SOZ detection on continuous data. Our sparse representation framework can also distinguish between ripples and fast ripples. Significance. We show that by using a sparse representation approach we can remove the pseudo-HFOs from the pool of events and improve the reliability of detected HFOs in large data sets and minimize manual artifact elimination.

Background Hypothalamic hamartomas (HH) are a challenging pathology that cause gelastic seizures. Magnetic Resonance Imaging-guided Laser Interstitial Thermal Therapy (MRgLITT) offers a safe and effective treatment for HHs via a minimally invasive technique. Objective To determine how clinical outcome correlates to residual tumor volume and surgical strategy by analyzing radiographic data and reconstructing volumetric imaging. Methods Clinical and radiographic information of 58 pediatric patients who underwent MRgLITT for HH with at least 6 mo of follow-up were retrospectively reviewed. MR imaging was volumetrically reconstructed to analyze the impact of hamartoma and ablation volumes on outcome. Primary outcome measure was freedom from gelastic seizures. Results Eighty-one percent of patients were completely free of gelastic seizures at last follow-up; of 22 patients with secondary nongelastic epilepsy, 15 were free of additional seizures. Postoperative complication rate was low. There was no significant difference in gelastic seizure outcome related to pre- or postoperative hamartoma size. Residual hamartoma percentage in those free of gelastic seizures was 43% compared to 71% in those with continued seizures (P = .021). Larger hamartomas required multiple ablations to achieve seizure freedom. Conclusion This large series of patients confirms the safety and efficacy of MRgLITT for pediatric HH and describes morphological considerations that predict success. Our data suggest that complete ablation of the lesion is not necessary, and that the focus should be on appropriate disconnection of the epileptogenic network. We have found that a staged approach to hamartoma ablation allows adequate disconnection of the hamartoma while mitigating risk to surrounding structures.

OBJECTIVEThe indication for and timing of surgery for epilepsy associated with low-grade mixed neuronal-glial tumors may be controversial. The purpose of this study was to evaluate the effect of resection and associated variables on epilepsy and on progression-free survival (PFS).METHODSA retrospective chart review of patients treated between 1992 and 2016 was conducted to identify individuals with epilepsy and low-grade gliomas or neuronal-glial tumors who underwent resective surgery. Data analyzed included age at epilepsy onset, age at surgery, extent of resection, use of electrocorticography, the number of antiepileptic drugs (AEDs) before and after surgery, the presence of dysplasia, Engel class, histological findings, and PFS. The institutional review board protocol was specifically approved to conduct this study.RESULTSA total of 107 patients were identified. The median follow-up was 4.9 years. The most common pathology was dysembryoplastic neuroepithelial tumor (36.4%), followed by ganglioglioma (31.8%). Eighty-four percent of patients had Engel class I outcomes following surgery. Gross-total resection was associated with a higher likelihood of an Engel class I outcome (90%) as compared to subtotal resection (58%) (p = 0.0005). Surgery reduced the AED burden, with 40% of patients requiring no AEDs after surgery (p < 0.0001). Children with neurodevelopmental comorbidities (n = 5) uniformly did not experience seizure improvement following resection (0% vs 83% overall; p < 0.0001). Electrocorticography was used in 33% of cases and did not significantly increase class I outcomes. PFS was 90% at 5 years. Eleven percent of tumors recurred, with subtotal resection more likely to result in recurrence (hazard ratio 5.3, p = 0.02). Histological subtype showed no significant impact on recurrence.CONCLUSIONSGross-total resection was strongly associated with Engel class I outcome and longer PFS. Further studies are needed to elucidate the suitable time for surgery and to identify factors associated with oncological transformation.

ObjectiveTo investigate the differences in delivery mode, daily dose, and catheter tip location in pediatric patients using intrathecal baclofen (ITB) pumps with spasticity plus dystonia versus spasticity alone.MethodsA single-center, cross-sectional study was performed by collecting retrospective data from electronic medical records. Demographic and diagnostic information was obtained, comparing patients with spasticity with or without dystonia. The data were analyzed for group differences using a two-tailed Student’s t-test. Categorical data were analyzed for group differences using Pearson’s χ2 test.ResultsA total of 137 patients met the criteria. The majority (114) had spasticity plus dystonia whereas only 23 were documented as spasticity alone. Simple continuous dosing was the most common delivery mode, but flex dosing was used more than twice as frequently with spasticity plus dystonia compared with spasticity alone (42% vs 17%). Patients with spasticity plus dystonia also had more rostral catheter tip locations.ConclusionsWhile it has been discussed anecdotally, this study confirms the supposition that patients with spasticity plus dystonia have increased dose requirements when compared with those with spasticity alone. Although there are no clear standards of care when managing these patients, they are often on higher daily dosages, are more likely to require flexed dosing method, and have higher catheter placements. Still, there are few studies that demonstrate improvements in dystonia with the use of ITB. In general, these patients would benefit from the development of universal standardizations as well as the confirmation that this is an appropriate treatment.

Texas Children’s Hospital opened its doors in 1954, and since that time the institution has remained dedicated to a three-part mission: patient care, education, and research. Dr. William R. Cheek developed an early interest in pediatric neurosurgery, which led to his efforts in building and developing a service at Texas Children’s Hospital at a time when the field was just emerging. His work with other early pioneers in the field led to the establishment of organized societies, educational texts, and governing bodies that have led to significant advances in the field over the past 50 years.

OBJECTIVE The grid-based orthogonal placement of depth electrodes (DEs), initially defined by Jean Talairach and Jean Bancaud, is known as stereo-electroencephalography (sEEG). Although acceptance in the United States was initially slow, advances in imaging and technology have spawned a proliferation of North American epilepsy centers offering sEEG. Despite publications highlighting minimal access techniques and varied indications, standard work for phase I targeted DE has not been defined. In this article, the authors propose the term “dynamic sEEG” and define standard work tools and related common data elements to promote uniformity in the field. METHODS A multidisciplinary approach from July to August 2016 resulted in the production of 4 standard work tools for dynamic sEEG using ROSA: 1) a 34-page illustrated manual depicting a detailed workflow; 2) a planning form to collocate all the phase I data; 3) a naming convention for DEs that encodes the data defining it; and 4) a reusable portable perioperative planning and documentation board. A retrospective review of sEEG case efficiency was performed comparing those using standard work tools (between July 2016 and April 2017) with historical controls (between March 2015 and June 2016). The standard work tools were then instituted at another epilepsy surgery center, and the results were recorded. RESULTS The process for dynamic sEEG was formally reviewed, including anesthesia, positioning, perioperative nursing guidelines, surgical steps, and postoperative care for the workflow using cranial fixation and ROSA-guided placement. There was a 40% improvement in time per electrode, from 44.7 ± 9.0 minutes to 26.9 ± 6.5 minutes (p = 0.0007) following the development and use of the manual, the naming convention, and the reusable portable perioperative planning and documentation board. This standardized protocol was implemented at another institution and yielded a time per electrode of 22.3 ± 4.4 minutes. CONCLUSIONS The authors propose the term dynamic sEEG for stereotactic depth electrodes placed according to phase I workup data with the intention of converting to ablation. This workflow efficiency can be optimized using the standard work tools presented. The authors also propose a novel naming convention that encodes critical data and allows portability among providers. Use of a planning form for common data elements optimizes research, and global adoption could facilitate multicenter studies correlating phase I modality and seizure onset zone identification.

Epilepsy occurs in nearly all patients with tuberous sclerosis and is often refractory to medical treatment. The definition of surgical candidacy in these patients has broadened in recent years due to philosophical and technological advances. The goals of surgery have shifted to focusing on quality of life and maximizing neurodevelopmental potential in patients unable to obtain seizure freedom. Novel diagnostic, ablative, and neuromodulatory techniques have been developed that may help patients that were previously considered inoperable to have an improved quality of life. In the coming years, it is expected that these techniques will be further refined and lead to an improvement of neurological prognosis in patients with tuberous sclerosis.

MRgLITT was first used for treatment of epilepsy in a child in 2010. Since that initial case, the technique has been applied to many pediatric epileptogenic targets such as tuberous sclerosis, mesial temporal lobe epilepsy, focal cortical dysplasia, periventricular nodular heterotopia, insular epilepsy, cavernous malformation, and, most efficiently, hypothalamic hamartoma. The combination of instant thermal ablation and peri-operative steroids to combat edema has resulted in an 83% 1-year seizure freedom rate with 1.5% rate of memory impairment, making it a profound improvement on open surgery. The technique has also been applied in disconnection, such as in corpus callosotomy, both in de novo and in salvage cases. In the treatment of drop attacks, three to four lasers can be employed to achieve the disconnection minimally invasively, obviating the need for a craniotomy. Outside of hypothalamic hamartoma, there have been few large pathology-based series, and long-term cognitive data is not available. MRgLITT in pediatric epilepsy holds the promise of less morbidity and shorter hospital stays, steps that may narrow the treatment gap in pediatric epilepsy surgery from anxiety and morbidity avoidance.

Hypothalamic hamartomas are rare lesions that are highly epileptogenic. The lesions are benign, heterotopic masses that occur due to anomalies in neuronal migration. They usually present as a specific epileptic syndrome characterized by laughing spells, and the epileptic syndromes can further generalize. The hamartomas are often small lesions that can be missed on magnetic resonance imaging, and their epileptic syndromes may not be easily localizable by scalp electroencephalography. Their hypothalamic location renders the open or endoscopic surgical approach challenging, with a significant amount of morbidity associated with it. The advent of laser thermal interstitial therapy has allowed treatment of these lesions with minimal morbidity and reasonable seizure control rates.

ObjectiveTo describe the findings of histopathology and genotyping studies in affected brain tissue from an individual with phacomatosis pigmentovascularis (PPV).MethodsA retrospective chart review of a 2-year 10-month-old male with a clinical diagnosis of PPV cesiomarmorata (or type V) was performed. Clinical features, brain imaging and histopathology findings, and genotyping studies in his affected brain tissue are summarized.ResultsThe proband had a clinically severe neurologic phenotype characterized by global developmental delay, generalized hypotonia, and recurrent episodes of cardiac asystole in the setting of status epilepticus. A somatic pathogenic variant in GNA11 (c.547C>T, p.Arg183Cys) was detected in his skin tissue but not in blood (previously published). He underwent an urgent left posterior quadrantectomy for his life-threatening seizures. Histopathology of resected brain tissue showed an increase in leptomeningeal melanocytes and abnormal vasculature, and the exact pathogenic variant in GNA11 (c.547C>T, p.Arg183Cys), previously isolated from his skin tissue but not blood, was detected in his resected brain tissue.ConclusionsThe finding of this variant in affected skin and brain tissue of our patient with PPV supports a unifying genetic diagnosis of his neurocutaneous features.

Stereotyped high-frequency oscillations discriminate seizure onset zones and critical functional cortex in focal epilepsy.Liu S, Gurses C, Sha Z, Quach MM, Sencer A, Bebek N, et al. Brain. 2018;141(3):713-730. doi:10.1093/brain/awx374. PMID: 29394328.High-frequency oscillations in local field potentials recorded with intracranial electroencephalogram are putative biomarkers of seizure-onset zones in epileptic brain. However, localized 80- to 500-Hz oscillations can also be recorded from normal and nonepileptic cerebral structures. When defined only by rate or frequency, physiological high-frequency oscillations are indistinguishable from pathological ones that limit their application in epilepsy presurgical planning. We hypothesized that pathological high-frequency oscillations occur in a repetitive fashion with a similar waveform morphology that specifically indicates seizure onset zones. We investigated the waveform patterns of automatically detected high-frequency oscillations in 13 patients with epilepsy and 5 control subjects, with an average of 73 subdural and intracerebral electrodes recorded per patient. The repetitive oscillatory waveforms were identified using a pipeline of unsupervised machine learning techniques and were then correlated with independently clinician-defined seizure onset zones. Consistently in all patients, the stereotypical high-frequency oscillations with the highest degree of waveform similarity were localized within the seizure onset zones only, whereas the channels generating high-frequency oscillations embedded in random waveforms were found in the functional regions independent of the epileptogenic locations. The repetitive waveform pattern was more evident in fast ripples compared to ripples, suggesting a potential association between waveform repetition and the underlying pathological network. Our findings provided a new tool for the interpretation of pathological high-frequency oscillations that can be efficiently applied to distinguish seizure onset zones from functionally important sites, which is a critical step toward the translation of these signature events into valid clinical biomarkers.

BACKGROUND Patients with metastatic pediatric ependymoma have limited therapeutic options and poor outcomes. Approximately ¾ of supratentorial ependymomas are driven by C11ORF95-RELA fusions, and the remaining by a heterogeneous group of fusion events. We present a six year-old male diagnosed with supratentorial ependymoma with leptomeningeal carcinomatosis harboring an NTRK2-fusion. Local and distant multifocal, intracranial and intraspinal tumor recurrence occurred seven months following gross total resection of the primary lesion and proton beam craniospinal irradiation. METHODS DNA and RNA from FFPE tumor were used for targeted sequencing using an 81-gene fusion panel and 124-gene mutation panel. Separately, capture transcriptome sequencing, exome sequencing, and copy number array were performed as part of the Texas KidsCanSeq study, an NHGRI/NCI-funded Clinical Sequencing Evidence-Generating Research (CSER) consortium project. All sequencing was carried out in CLIA-certified laboratories. RESULTS An in-frame fusion between 5’ exons 1–3 of KANK1 and 3’ exons 16–21 of NTRK2, predicted to retain the kinase domain, was identified. At tumor recurrence, therapy was initiated with Larotrectinib, an FDA-approved pan-TRK inhibitor. Clinical improvement in cognitive speed, motor strength, and coordination was observed at two weeks with significant tumor response on MRI at two and four months. CONCLUSION TRK gene fusions have not previously been reported in ependymoma. Further tumor characterization by methylation profiling is underway and will be of diagnostic interest given the apparent discordance between tumor histology and molecular findings. This case highlights the potential impact of clinical genomic analysis for children with CNS tumors.

In selected children with tuberous sclerosis complex, epilepsy surgery leads to seizure freedom or seizure reduction. The current standard involves a multimodal pre-surgical workup followed by invasive electrocorticographic monitoring and resective surgery. Recent insights in the disorder and novel technologies are changing the approach to pediatric epilepsy surgery in tuberous sclerosis complex. New evidence suggests tubers are poorly delineated, and epileptogenic activity may originate in the perituber tissue. Novel imaging modalities relevant to surgical planning include high-resolution MRI, α-methyl-l-tryptophan or fluorodeoxyglucose PET with diffusion tensor imaging. Advanced neurophysiological techniques have improved identification of the surgical target, including magnetoencephalography, electrical source imaging of high-density electroencephalograph data, and high-frequency oscillations in electrocorticography data. Simultaneously, novel surgical tools including stereo-electroencephalography and laser-induced thermal therapy have become available for children. This article reviews the literature in the light of these rapidly changing technologies.

Summary Epilepsy associated with cavernous malformation (CM) often requires surgical resection of seizure focus to achieve seizure‐free outcome. High‐frequency oscillations (HFOs) in intracranial electroencephalogram (EEG) are reported as potential biomarkers of epileptogenic regions, but to our knowledge there are no data on the existence of HFOs in CM‐caused epilepsy. Here we report our experience of the identification of the seizure focus in a 3‐year‐old pediatric patient with intractable epilepsy associated with CM. The electrocorticographic recordings were obtained from a 64‐contact grid over 2 days in the epilepsy monitoring unit (EMU). The spatial distribution of HFOs and epileptic spikes were estimated from recording segments right after the electrode placement, during sleep and awake states separately. The HFO distribution showed consistency with the perilesional region; the location of spikes varied over days and did not correlate with the lesion. The HFO spatial distribution was more compact in sleep state and pinpointed the contacts sitting on the CM border. Following the resection of the CM and the hemosiderin ring, the patient became seizure‐free. This is the first report describing HFOs in a pediatric patient with intractable epilepsy associated with CM and shows their potential in identifying the seizure focus.

Hypothalamic hamartoma (HH) is a congenital intracranial lesion associated with precocious puberty and gelastic epilepsy in children. Surgical management of HH to treat refractory epilepsy is a mainstay of treatment. Our aim was to compare the demographic characteristics and perioperative costs associated with resection by craniotomy and stereotactic laser ablation (SLA) by reviewing our institutional experience with SLA and comparing these data to a national database for craniotomy and resection. Retrospective chart review was conducted for the Texas Children's Hospital cohort of patients who underwent SLA for HH between 2011 and 2013. Information about the craniotomy cohort representing historical cases of craniotomy was obtained from the Kids' Inpatient Database for years 2003, 2006, and 2009. The cohort definition for patients undergoing craniotomy for HH was modified from published adult literature to identify pediatric patients with refractory epilepsy secondary to HH. Our study has shown that children undergoing SLA for HH have a shorter length of stay and lower cost of hospitalization compared with those who underwent craniotomy and resection for the same diagnosis. Together with previous findings from our institution regarding the safety and efficacy of SLA, our findings suggest that SLA may represent an attractive alternative to craniotomy for the treatment of refractory epilepsy secondary to HH.

ANK3, encoding the adaptor protein Ankyrin-G, has been implicated in bipolar disorder by genome wide association studies. ANK3 has multiple alternative first exons, and a bipolar disorder-associated ANK3 variant has been shown to reduce expression of exon 1b. Here we identify mechanisms through which reduced ANK3 exon 1b isoform expression disrupts neuronal excitation-inhibition balance. We find that parvalbumin interneurons and principal cells differentially express ANK3 first exon subtypes. Parvalbumin interneurons express only isoforms containing exon 1b, whereas excitatory principal cells express exon 1e alone, or both 1e and 1b. In transgenic mice deficient for exon 1b, parvalbumin interneurons lack voltage-gated sodium channels at their axonal initial segments and have increased firing thresholds and diminished action potential dynamic range. These mice exhibit an Ank3 gene dosage-dependent phenotype including behavior changes modeling bipolar disorder, epilepsy, and sudden death. Thus, ANK3’s important association with human bipolar susceptibility may arise from imbalance between ankyrin-G function in interneurons and principal cells and resultant excessive circuit sensitivity and output. Ankyrin-G isoform imbalance is a novel molecular endophenotype and potential therapeutic target.

The aims of this study were to evaluate a clinically practical functional connectivity protocol designed to blindly identify the corresponding areas of initial seizure propagation and also to differentiate these areas from remote secondary areas affected by seizure. The patients in this cohort had intractable epilepsy caused by intrahypothalamic hamartoma, which is the location of the ictal focus. The ictal propagation pathway is homogeneous and established, thus creating the optimum situation for the proposed method validation study.Twelve patients with seizures from hypothalamic hamartoma and 6 normal control patients underwent resting state functional MRI, using independent component analysis to identify network differences in patients. This was followed by seed-based connectivity measures to determine the extent of functional connectivity derangement between hypothalamus and these areas. The areas with significant change in connectivity were compared with the results of prior studies' modalities used to evaluate seizure propagation.The left amygdala-parahippocampal gyrus area, cingulate gyrus, and occipito-temporal gyrus demonstrated the highest derangement in connectivity with the hypothalamus, p0.01, corresponding to the initial seizure propagation areas established by prior modalities. Areas of secondary ictal propagation were differentiated from these initial locations by first being identified as an abnormal neuronal signal source via independent component analysis, but did not show significant connectivity directly with the known ictal focus.Non-invasive connectivity measures correspond to areas of initial ictal propagation and differentiate such areas from secondary ictal propagation, which may aid in ictal focus surgical disconnection planning and support the use of this newer modality for adjunctive information in epilepsy surgery evaluation.

OBJECTIVE Postoperative resting-state functional magnetic resonance imaging (MRI) in children with intractable epilepsy has not been quantified in relation to seizure outcome. Therefore, its value as a biomarker for epileptogenic pathology is not well understood. METHODS In a sample of children with intractable epilepsy who underwent prospective resting-state seizure onset zone (SOZ)-targeted epilepsy surgery, postoperative resting-state functional MRI (rs-fMRI) was performed 6 to 12 months later. Graded normalization of the postoperative resting-state SOZ was compared to seizure outcomes, patient, surgery, and anatomical MRI characteristics. RESULTS A total of 64 cases were evaluated. Network-targeted surgery, followed by postoperative rs-fMRI normalization was significantly (p < 0.001) correlated with seizure reduction, with a Spearman rank correlation coefficient of 0.83. Of 39 cases with postoperative rs-fMRI SOZ normalization, 38 (97%) became completely seizure free. In contrast, of the 25 cases without complete rs-fMRI SOZ normalization, only 3 (5%) became seizure free. The accuracy of rs-fMRI as a biomarker predicting seizure freedom is 94%, with 96% sensitivity and 93% specificity. INTERPRETATION Among seizure localization techniques in pediatric epilepsy, network-targeted surgery, followed by postoperative rs-fMRI normalization, has high correlation with seizure freedom. This study shows that rs-fMRI SOZ can be used as a biomarker of the epileptogenic zone, and postoperative rs-fMRI normalization is a biomarker for SOZ quiescence. ANN NEUROL 2019;86:344-356.

Background Tethered cord syndrome (TCS) refers to a clinical constellation of signs and symptoms associated with tension in the spinal cord and associated with pathologies related to abnormally low-lying conus medullaris. As minimally invasive spinal operations have become more prevalent in the past decade, we applied expanding indications to selected intradural procedures, such as tethered cord release (TCR). We present the first series of minimally invasive muscle-sparing TCR in the pediatric population. Methods A retrospective review of the Texas Children's Hospital, Houston, neurosurgical database was conducted for patients who underwent TCR between 2010 and 2017. Charts were reviewed to determine the source of TCS and whether surgery was conducted in a minimally invasive fashion. To establish a cohort of control population, age-matched cases of open TCR were selected in the same. Exclusion criterion was non-fatty filum sources of TCS. The length of stay, operative time, estimated blood loss, and postoperative complications were recorded. Results Eleven patients underwent minimally invasive TCR. Mean age of the patients was 10.1 years. All patients underwent L4-5 tubular laminotomy and cord detethering by 2 pediatric neurosurgeons at Texas Children's Hospital. The average length of stay in the hospital was 2.6 days. The average operative time was 167 minutes and average estimated blood loss was 8.2 mL. Ten patients reported clinical improvement and 1 patient was lost to follow-up. Conclusions Minimally invasive TCR is a safe and represents a viable alternative to the open approach with advantages such as minimal estimated blood loss, shortened length of stay, and postoperative pain control.

The vagus nerve stimulator (VNS) has been shown to provide a safe, albeit costly, treatment for intractable epilepsy. We aimed to analyze the incidence, timing, and clinical/demographic associations of revision surgery post-VNS implantation in epilepsy patients. The Thomson Reuters MarketScan database, containing data from 23-50million individuals, was used. Epilepsy patients receiving VNS implantations from 2003 to 2009 were identified by Current Procedural Terminology and International Classification Of Diseases Ninth Revision codes. Incidence and timing of subsequent implant-related surgeries were recorded. Events were described using time-to-event methodology, with Kaplan-Meier failure estimation/Cox proportional hazard models adjusted for clinical/demographic factors. In 1234 patients, average incidence of revision surgeries over 6years of follow-up were

Deep brain stimulation (DBS) has improved the prospects for many individuals with diseases affecting motor control, and recently it has shown promise for improving cognitive function as well. Several studies in individuals with Alzheimer disease and in amnesic rats have demonstrated that DBS targeted to the fimbria-fornix, the region that appears to regulate hippocampal activity, can mitigate defects in hippocampus-dependent memory. Despite these promising results, DBS has not been tested for its ability to improve cognition in any childhood intellectual disability disorder. Such disorders are a pressing concern: they affect as much as 3% of the population and involve hundreds of different genes. We proposed that stimulating the neural circuits that underlie learning and memory might provide a more promising route to treating these otherwise intractable disorders than seeking to adjust levels of one molecule at a time. We therefore studied the effects of forniceal DBS in a well-characterized mouse model of Rett syndrome (RTT), which is a leading cause of intellectual disability in females. Caused by mutations that impair the function of MeCP2 (ref. 6), RTT appears by the second year of life in humans, causing profound impairment in cognitive, motor and social skills, along with an array of neurological features. RTT mice, which reproduce the broad phenotype of this disorder, also show clear deficits in hippocampus-dependent learning and memory and hippocampal synaptic plasticity. Here we show that forniceal DBS in RTT mice rescues contextual fear memory as well as spatial learning and memory. In parallel, forniceal DBS restores in vivo hippocampal long-term potentiation and hippocampal neurogenesis. These results indicate that forniceal DBS might mitigate cognitive dysfunction in RTT.

OBJECTIVE The purpose of this study is to investigate the outcomes of epilepsy surgery targeting the subcentimeter-sized resting state functional magnetic resonance imaging (rs-fMRI) epileptogenic onset zone (EZ) in hypothalamic hamartoma (HH). METHODS Fifty-one children with HH-related intractable epilepsy received anatomical MRI-guided stereotactic laser ablation (SLA) procedures. Fifteen of these children were control subjects (CS) not guided by rs-fMRI. Thirty-six had been preoperatively guided by rs-fMRI (RS) to determine EZs, which were subsequently targeted by SLA. The primary outcome measure for the study was a predetermined goal of 30% reduction in seizure frequency and improvement in class I Engel outcomes 1 year postoperatively. Quantitative and qualitative volumetric analyses of total HH and ablated tissue were also assessed. RESULTS In the RS group, the EZ target within the HH was ablated with high accuracy (>87.5% of target ablated in 83% of subjects). There was no difference between the groups in percentage of ablated hamartoma volume (P = 0.137). Overall seizure reduction was higher in the rs-fMRI group: 85% RS versus 49% CS (P = 0.0006, adjusted). The Engel Epilepsy Surgery Outcome Scale demonstrated significant differences in those with freedom from disabling seizures (class I), 92% RS versus 47% CS, a 45% improvement (P = 0.001). Compared to prior studies, there was improvement in class I outcomes (92% vs 76%-81%). No postoperative morbidity or mortality occurred. SIGNIFICANCE For the first time, surgical SLA targeting of subcentimeter-sized EZs, located by rs-fMRI, guided surgery for intractable epilepsy. Our outcomes demonstrated the highest seizure freedom rate without surgical complications and are a significant improvement over prior reports. The approach improved freedom from seizures by 45% compared to conventional ablation, regardless of hamartoma size or anatomical classification. This technique showed the same or reduced morbidity (0%) compared to recent non-rs-fMRI-guided SLA studies with as high as 20% permanent significant morbidity.

OBJECTIVEDetermining language laterality in patients with intractable epilepsy is important in operative planning. Wada testing is the gold standard, but it has a risk of stroke. Both Wada and task-based functional MRI (tb-fMRI) require patient cooperation. Recently, resting-state fMRI (rs-fMRI) has been explored for language lateralization. In the present study, the correlation between rs-fMRI and tb-fMRI in language lateralization is estimated in a pediatric population with intractable epilepsy.METHODSrs-fMRI and tb-fMRI language lateralization testing performed as part of epilepsy surgery evaluation was retrospectively reviewed.RESULTSTwenty-nine patients underwent rs-fMRI and tb-fMRI; a total of 38 rs-fMRI studies and 30 tb-fMRI studies were obtained. tb-fMRI suggested left dominance in 25 of 30 cases (83%), right in 3 (10%), and in 2 (7%) the studies were nondiagnostic. In rs-fMRI, 26 of 38 studies (68%) suggested left dominance, 3 (8%) right dominance, 6 (16%) bilateral, and 3 (8%) were nondiagnostic. When tb-fMRI lateralized to the left hemisphere (25 cases), rs-fMRI was lateralized to the left in 23 patients (92%) and it was bilateral/equal in 2 (8%). When tb-fMRI lateralized to the right (3 cases), rs-fMRI lateralized to the right in all cases (100%). The overall concordance rate was 0.93 (95% CI 0.76–0.99) when considering cases with tb-fMRI and rs-fMRI performed within 6 months of each other, and tb-fMRI results were not nondiagnostic.CONCLUSIONSrs-fMRI significantly correlated with tb-fMRI in lateralizing language and suggests the potential role for identifying hemispheric dominance via rs-fMRI. Further investigation and validation studies are warranted.

Hypothalamic hamartoma is an archetypal example of subcortical epilepsy that can be associated with intractable gelastic epilepsy, secondary epilepsy, and epileptic encephalopathy. The history of its surgical treatment is fraught with mislocalization of the seizure focus, modest efficacy and a high complication rate. Many minimally invasive techniques have been described to mitigate this high complication profile of which MR-guided laser ablation is one. The technology combines instant effect of thermal coagulation with stereotactic precision and guidance with real time MR thermography. This article presents a series of 71 hypothalamic hamartoma patients operated with laser ablation. Ninety-three percent (93%) were free of gelastic seizures at one year with 23% of the patients requiring more than one ablation. One patient experienced a significant memory deficit and one patient experienced worsening diabetes insipidus. Stereotactic laser ablation appears to be a safe and effective surgical option in the treatment of hypothalamic hamartoma.

Neuropathology of resected brain tissue has revealed an association of focal cortical dysplasia (FCD) with drug-resistant epilepsy (DRE). Recent studies have shown that the mechanistic target of rapamycin (mTOR) pathway is hyperactivated in FCD as evidenced by increased phosphorylation of the ribosomal protein S6 (S6) at serine 240/244 (S(240/244) ), a downstream target of mTOR. Moreover, extracellular regulated kinase (ERK) has been shown to phosphorylate S6 at serine 235/236 (S(235/236) ) and tuberous sclerosis complex 2 (TSC2) at serine 664 (S(664) ) leading to hyperactive mTOR signaling. We evaluated ERK phosphorylation of S6 and TSC2 in two types of FCD (FCD I and FCD II) as a candidate mechanism contributing to mTOR pathway dysregulation. Tissue samples from patients with tuberous sclerosis (TS) served as a positive control. Immunostaining for phospho-S6 (pS6(240/244) and pS6(235/236) ), phospho-ERK (pERK), and phospho-TSC2 (pTSC2) was performed on resected brain tissue with FCD and TS. We found increased pS6(240/244) and pS6(235/236) staining in FCD I, FCD II and TS compared to normal-appearing tissue, while pERK and pTSC2 staining was increased only in FCD IIb and TS tissue. Our results suggest that both the ERK and mTOR pathways are dysregulated in FCD and TS; however, the signaling alterations are different for FCD I as compared to FCD II and TS.

MRI-guided laser interstitial thermal therapy for epilepsy (LITT-E) has become an established, minimally invasive alternative to traditional epilepsy surgery. LITT-E is particularly valuable in cases in which open surgery poses unacceptably high morbidity or patient preference precludes craniotomy. Here we present a focused review of technical details and application of LITT to both focal and generalized epilepsy.

Resting-state functional magnetic resonance imaging (rsfMRI) is emerging as a useful tool in the multimodal assessment of patients with epilepsy. In pediatric patients who cannot perform task-based fMRI, rsfMRI may present an adjunct and alternative. Although changes in brain activation during task-based fMRI have been described after surgery for epilepsy, there is limited data on the role of postoperative rsfMRI. In this short review, we discuss the role of postoperative rsfMRI after laser ablation of seizure foci. By establishing standardized anesthesia protocols and imaging parameters, we have been able to perform serial rsfMRI at postoperative follow-up. The development of in-house software that can merge rsfMRI images to surgical navigation systems has allowed us to enhance the clinical applications of this technique. Resting-state fMRI after laser ablation has the potential to identify changes in connectivity, localize new seizure foci, and guide antiepileptic therapy. In our experience, rsfMRI complements conventional MR imaging and task-based fMRI for the evaluation of patients with seizure recurrence after laser ablation, and represents a potential noninvasive biomarker for functional connectivity.

Preoperative antibiosis contributes up to one third of total antibiotic use in major hospitals. Choice of antibiotic is not uniformly standardized, and polypharmacy regimens may be used without knowing the effect on rates of surgical site infection, nonsurgical infections, or antibiotic resistance. Careful examination of trends in surgical prophylaxis is warranted. In this study, we aimed to examine our institution’s experience with vagus nerve stimulator (VNS) implantation, focusing on association between perioperative antibiotic practices and postoperative infectious outcomes. We conducted a single-center case-control study using a retrospective chart review of 50 consecutively operated patients undergoing VNS implantation over 24 months by two experienced surgeons at our institution from April 2014 to March 2016. In each surgery, the technical procedure, operating room, and surgical team were the same, while surgeon’s preference in antibiotic prophylaxis differed. Group 1 received a single dose of intravenous (IV) cefazolin (n = 26), and Group 2 received IV cefazolin, paired with one or both of gentamicin/vancomycin, in addition to a 10-day outpatient oral course of clindamycin (n = 24). Patient demographics, perioperative details, and minimum 3-month follow-up for infection and healthcare utilization were recorded. Student t tests were computed for significance. Group 1 patients on average were older than group 2 patients (10.2, 7.1 years, p = 0.01), and length of surgery was longer (115.5, 91.9 min, p = 0.007). There were no differences in number of surgeons gowned (p = 0.11), presence of tracheostomy (p = 0.43) or gastrostomy (p = 0.20) tube, nonsurgical infections (p = 0.32), and number of postoperative emergency department (ED) visits (p = 0.22) or readmissions (p = 0.23). Neither group had VNS infections in the follow-up period. Single preoperative dosing of one antibiotic appropriately chosen to cover typical skin flora conferred equal benefit to perioperative prophylactic polypharmacy in this study. There were no differences in postoperative infection events or ED visits/readmissions. Restraint with preoperative antibiosis shows equipoise in postoperative infection and overall resource utilization.

Object Deep brain stimulation (DBS) has become accepted therapy for intractable dystonia and other movement disorders. The accurate placement of DBS electrodes into the globus pallidus internus is assisted by unimpaired microelectrode recordings (MERs). Many anesthetic and sedative drugs interfere with MERs, requiring the patient to be awake for target localization and neurological testing during the procedure. In this study, a novel anesthetic technique was investigated in pediatric DBS to preserve MERs. Methods In this paper, the authors describe a sedative/anesthetic technique using ketamine, remifentanil, dexmedetomidine, and nicardipine in 6 pediatric patients, in whom the avoidance of GABAergic stimulating drugs permitted excellent surgical conditions with no detrimental effects on intraoperative MERs. The quality of the MERs, and the frequency of its use in making electrode placement decisions, was reviewed. Results All 6 patients had good-quality MERs. The data were of sufficient quality to make a total of 9 trajectory adjustments. Conclusions Microelectrode recordings in pediatric DBS can be preserved with a combination of dexmedetomidine and ketamine, remifentanil, and nicardipine. This preservation of MERs is particularly crucial in electrode placement in children.

Congenital hydrocephalus, the accumulation of excess cerebrospinal fluid (CSF) in the ventricles of the brain, affects one of every 1000 children born today, making it one of the most common human developmental disorders. Genetic causes of hydrocephalus are poorly understood in humans, but animal models suggest a broad genetic program underlying the regulation of CSF balance. In this study, the random integration of a transgene into the mouse genome led to the development of an early onset and rapidly progressive hydrocephalus. Juvenile hydrocephalus transgenic mice (Jhy(lacZ)) inherit communicating hydrocephalus in an autosomal recessive fashion with dilation of the lateral ventricles observed as early as postnatal day 1.5. Ventricular dilation increases in severity over time, becoming fatal at 4-8 weeks of age. The ependymal cilia lining the lateral ventricles are morphologically abnormal and reduced in number in Jhy(lacZ/lacZ) brains, and ultrastructural analysis revealed disorganization of the expected 9+2 microtubule pattern. Rather, the majority of Jhy(lacZ/lacZ) cilia develop axonemes with 9+0 or 8+2 microtubule structures. Disruption of an unstudied gene, 4931429I11Rik (now named Jhy) appears to underlie the hydrocephalus of Jhy(lacZ/lacZ) mice, and the Jhy transcript and protein are decreased in Jhy(lacZ/lacZ) mice. Partial phenotypic rescue was achieved in Jhy(lacZ/lacZ) mice by the introduction of a bacterial artificial chromosome (BAC) carrying 60-70% of the JHY protein coding sequence. Jhy is evolutionarily conserved from humans to basal vertebrates, but the predicted JHY protein lacks identifiable functional domains. Ongoing studies are directed at uncovering the physiological function of JHY and its role in CSF homeostasis.