Predictors of therapeutic response following thalamic neuromodulation for drug-resistant pediatric epilepsy: A systematic review and individual patient data meta-analysis.

We sought to perform a systematic review and individual participant data meta-analysis to identify predictors of treatment response following thalamic neuromodulation in pediatric patients with medically refractory epilepsy. Electronic databases (MEDLINE, Ovid, Embase, and Cochrane) were searched, with no language or data restriction, to identify studies reporting seizure outcomes in pediatric populations following deep brain stimulation (DBS) or responsive neurostimulation (RNS) implantation in thalamic nuclei. Studies featuring individual participant data of patients with primary or secondary generalized drug-resistant epilepsy were included. Response to therapy was defined as >50% reduction in seizure frequency from baseline. Of 417 citations, 21 articles reporting on 88 participants were eligible. Mean age at implantation was 13.07 ± 3.49 years. Fifty (57%) patients underwent DBS, and 38 (43%) RNS. Sixty (68%) patients were implanted in centromedian nucleus and 23 (26%) in anterior thalamic nucleus, and five (6%) had both targets implanted. Seventy-four (84%) patients were implanted bilaterally. The median time to last follow-up was 12 months (interquartile range = 6.75-26.25). Sixty-nine percent of patients achieved response to treatment. Age, target, modality, and laterality had no significant association with response in univariate logistic regression. Until thalamic neuromodulation gains widespread approval for use in pediatric patients, data on efficacy will continue to be limited to small retrospective cohorts and case series. The inherent bias of these studies can be overcome by using individual participant data. Thalamic neuromodulation appears to be a safe and effective treatment for epilepsy. Larger, prolonged prospective, multicenter studies are warranted to further evaluate the efficacy of DBS over RNS in this patient population where resection for curative intent is not a safe option.

Postoperative shunt failure following hemispherectomy in pediatric patients with pre-existing hydrocephalus.

OBJECTIVE: The risk of hydrocephalus following hemispherectomy for drug resistant epilepsy (DRE) remains high. Patients with pre-existing hydrocephalus pose a postoperative challenge, as maintaining existing shunt patency is necessary but lacks a clearly defined strategy. This study examines the incidence and predictors of shunt failure in pediatric hemispherectomy patients with pre-existing ventricular shunts. METHODS: We performed a retrospective chart review at our center to identify pediatric patients diagnosed with DRE who were treated with ventricular shunt prior to their first hemispherectomy surgery. Demographic and perioperative data were obtained including shunt history, hydrocephalus etiology, epilepsy duration, surgical technique, and postoperative outcomes. Univariate analysis was performed using Fisher's exact test and Pearson correlation, with Bonferroni correction to a = 0.00625 and a = 0.01, respectively. RESULTS: Five of nineteen (26.3%) patients identified with ventriculoperitoneal shunting prior to hemispherectomy experienced postoperative shunt malfunction. All 5 of these patients underwent at least 1 shunt revision prior to hemispherectomy, with a significant association between pre- and post-hemispherectomy shunt revisions. There was no significant association between post-hemispherectomy shunt failure and valve type, intraoperative shunt alteration, postoperative external ventricular drain placement, hemispherectomy revision, lateralization of shunt relative to resection, postoperative complications, or postoperative aseptic meningitis. There was no significant correlation between number of post-hemispherectomy shunt revisions and age at shunt placement, age at hemispherectomy, epilepsy duration, or shunt duration prior to hemispherectomy. CONCLUSIONS: Earlier shunt revision surgery may portend a subsequent need for shunt revision following hemispherectomy. These findings may guide neurosurgeons in counseling patients with pre-existing ventricular shunts prior to hemispherectomy surgery.

Hemispherectomy for hemimegalencephaly in a 6.5-week-old infant with tuberous sclerosis complex.

The aim of this report is to present a unique case of hemimegalencephaly and concomitant tuberous sclerosis complex (TSC1 mutation) with severe neonatal-onset epilepsy, which successfully underwent an anatomical hemispherectomy at 6.5 weeks of age for refractory seizures. Genetic testing confirmed a rare pathogenic, sporadic, heterozygous c.2041 + 1G > A gene mutation in intron 16 of the TSC1 gene, diagnostic for tuberous sclerosis. Post-operatively, the infant remained seizure free for at least 1 year. Following recurrence of her seizures, she has continued on multiple anti-seizure medications and everolimus therapy. We review the pathological and molecular features of this condition and highlight the ethics of intervention and steps taken toward safe neurosurgical intervention in this very young infant.

Paediatric epilepsy surgery: Techniques and outcomes.

Epilepsy is a neurological condition characterised by recurrent and persistent seizures. For paediatric patients, achieving early seizure freedom can have positive impacts on cognition, development, social integration and mental health, leading to improved quality of life. In general, one third of patients with epilepsy are refractory to medication; for these patients, epilepsy surgery may offer the only chance for improved seizure control. Epilepsy surgery as a therapeutic intervention has become increasingly accepted in the past few decades, with more diverse options available (including neuromodulatory and minimally invasive techniques). In this context, we discuss here the pre-operative workup for paediatric patients with medically refractory epilepsy and provide an updated review on current and emerging surgical therapies for this condition. We also discuss the clinical, neuropsychological, quality of life and economic impacts of epilepsy surgery.

Acute Myeloid Leukemia Presenting as a Posterior Fossa Tumor.

Extramedullary leukemia in pediatric acute myeloid leukemia can manifest as a myeloid sarcoma (MS), also known as granulocytic sarcoma or chloroma, in a variety of sites, or as leukemic blasts in the cerebrospinal fluid. Isolated MS of the central nervous system is rare. We report a case of acute myeloid leukemia with central nervous system-MS presenting as a posterior fossa mass mimicking a primary intracranial tumor.

Survey of epilepsy and seizure awareness in Manitoba: An evaluation.

BACKGROUND: Epilepsy and seizure awareness is gradually improving across Canada. With the strategic proposal for a Comprehensive Epilepsy Program in Manitoba (including formation of a new Pediatric Epilepsy Monitoring Unit (EMU)), a provincial strategy has been recommended outlining a path towards improved access to epilepsy care. We sought to qualify the current state of clinician knowledge and comfort towards diagnosis and management of this condition. METHODS: A qualitative online survey (Survey of Epilepsy and Seizure Awareness in Manitoba: An Evaluation (SESAME)), comprised of 36 short-answer questions, was delivered to primary care and specialist physicians in Manitoba. RESULTS: One hundred and eight subjects responded across varying medical disciplines. One hundred and one (93.5%) had previously managed patients with epilepsy, and 87 (80.6%) had previously ordered an electroencephalogram (EEG). A total of 63 (59.4%) had referred to a neurologist, with a lower proportion (30, 28.3%) referring specifically to an epileptologist. Only 36 respondents (33.3%) had heard of the International League Against Epilepsy (ILAE) guidelines. A total of 61 (56.5%) were unaware of invasive EEG techniques. Most (85, 78.7%) understood a role for surgery in treating epilepsy, with 12 (11.1%) unaware of surgical therapies beyond vagal nerve stimulation (VNS). Finally, less than half (44.2%) had heard about the Comprehensive Epilepsy Program in Manitoba, with nearly two-thirds (62.8%) indicating that they would like to have more information on epilepsy management. CONCLUSIONS: The SESAME successfully identified strong awareness towards epilepsy, with identifiable lapses in knowledge that will benefit from a formal provincial-wide educational curriculum.

Radiosurgery for mesial temporal lobe epilepsy following ROSE trial guidelines - A planning comparison between Gamma Knife, Eclipse, and Brainlab.

PURPOSE: This study aims to compare stereotactic radiosurgery (SRS) planning of epilepsy that complies with Radiosurgery or Open Surgery for Epilepsy (ROSE) guidelines in GammaKnife, non-coplanar conformal (NCC) plan in Eclipse, dynamic conformal arc (DCA) plan in Brainlab, and a volumetric modulated arc therapy (VMAT) plan in Eclipse. METHODS: Twenty plans targeting Mesial temporal lobe epilepsy (MTLE) was generated using GammaKnife, Eclipse with 20 NCC beams, Brainlab with 5 DCA, and Eclipse VMAT with 4 arcs observing ROSE trial guidelines. Multivariate analysis of variance and Wilcoxon signed-rank test were used to compare dosimetric data of the plans and perform pairwise comparison, respectively. RESULTS: The plans obeyed the recommended prescription isodose volume (PIV) within 5.5-7.5 cc and maximum doses to brainstem, optic apparatus (OA) of 10 and 8 Gy, respectively, for a prescription dose of 24 Gy. The volumes of the target were in the range 4.0-7.4 cc. Mean PIV, maximum dose to brainstem, OA were 6.5 cc, 10 Gy, 7.9 Gy in GammaKnife; 7.2 cc, 6.1 Gy, 4.5 Gy in Eclipse NCC; 7.2 cc, 6.4 Gy, 5.7 Gy in Brainlab DCA; and 5.2 cc, 8.4 Gy, 6.1 Gy in Eclipse VMAT plans, respectively. Multivariate analysis of variance showed significant differences among the 4 SRS planning techniques (P-values < 0.01). CONCLUSIONS: Among the 4 SRS planning methods, VMAT with least PIV and acceptable maximum doses to brainstem and OA showed highest compliance with ROSE trial. Having the most conformal dose distribution and least dose inhomogeneity, VMAT scored higher than GK, Eclipse NCC, and Brainlab DCA plans.

Giant Recurrent Supratentorial Neurenteric Cyst As a Cause of Medically Refractory Epilepsy.

We report on a unique case of a giant, recurrent, supratentorial neurenteric cyst causing intractable eplipsy. Following resection, the patient developed a delayed reactive cerebritis with focal edema and worsened seizures that fully resolved with medical management. At last follow-up, over 18 months later, the patient has no evidence for cyst recurrence and remains seizure-free. we conclude that complete resection of these lesions not only requires fenestration, but also microsurgical stripping of the cyst wall. Moreover, post-operative management inclues monitoring for worsened seizures as a consequence of intracranial exposure to the cystic contents and subsequent reactive cerebritis.

Radiosurgery in the Management of Intractable Mesial Temporal Lobe Epilepsy.

Mesial temporal lobe epilepsy (MTLE) describes recurrent seizure activity originating from the depths of the temporal lobe. MTLE patients who fail two trials of medication now require testing for surgical candidacy at an epilepsy center. For these individuals, temporal lobectomy offers the greatest likelihood for seizure-freedom (up to 80-90%); unfortunately, this procedure remains largely underutilized. Moreover, for select patients unable to tolerate open surgery, novel techniques are emerging for selective ablation of the mesial temporal structures, including stereotactic radiosurgery (SRS). We present here a review of SRS as a potential therapy for MTLE, when open surgery is not an option.

Disconnective Hemispherotomy for Medically Intractable Status Epilepticus in an 8-Year-Old Child.

We report here the unusual case of an 8-year-old child with left hemispheric focal epilepsy secondary to a perinatal infarction who presented with new onset absence seizures and eventual nonconvulsive status epilepticus that was refractory to medical management. Following review at our multidisciplinary Epilepsy Surgery conference, the patient underwent disconnective surgical hemispherotomy with immediate cessation of his seizures; and has remained seizure-free at 4 months following surgery. In this context, we present here an overview of hemispherectomy and related procedures, including peri-insular disconnective hemispherotomy, and we discuss the efficacy of surgery for challenging hemispheric epilepsies.

Disconnective hemispherotomy: technique and operative highlights.

Hemispherectomy is an effective procedure used in the treatment of drug-resistant hemispheric epilepsy, especially in the pediatric population. A number of resective and disconnective techniques are used, and selection of surgical strategy is paramount to achieving successful results. Notably, disconnective (or functional) hemispherotomy maximizes the benefits of safe, surgical disconnection while minimizing hemispheric tissue resection, thereby avoiding some of the perioperative factors contributing to morbidity in traditional anatomical hemispherectomy procedures. In this video, the authors outline the principal surgical steps of disconnective hemispherotomy and highlight important technical factors leading to optimal outcomes in patients with refractory, oftentimes catastrophic, hemispheric epilepsy. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2436.

Measurable transitions during seizures in intracranial EEG: A stereoelectroencephalography and SPECT study.

OBJECTIVE: Ictal Single Photon Emission Computed Tomography (SPECT) and stereo-electroencephalography (SEEG) are diagnostic techniques used for the management of patients with drug-resistant focal epilepsies. While hyperperfusion patterns in ictal SPECT studies reveal seizure onset and propagation pathways, the role of ictal hypoperfusion remains poorly understood. The goal of this study was to systematically characterize the spatio-temporal information flow dynamics between differently perfused brain regions using stereo-EEG recordings. METHODS: We identified seizure-free patients after resective epilepsy surgery who had prior ictal SPECT and SEEG investigations. We estimated directional connectivity between the epileptogenic-zone (EZ), non-resected areas of hyperperfusion, hypoperfusion, and baseline perfusion during the interictal, preictal, ictal, and postictal periods. RESULTS: Compared to the background, we noted significant information flow (1) during the preictal period from the EZ to the baseline and hyperperfused regions, (2) during the ictal onset from the EZ to all three regions, and (3) during the period of seizure evolution from the area of hypoperfusion to all three regions. CONCLUSIONS: Hypoperfused brain regions were found to indirectly interact with the EZ during the ictal period. SIGNIFICANCE: Our unique study, combining intracranial electrophysiology and perfusion imaging, presents compelling evidence of dynamic changes in directional connectivity between brain regions during the transition from interictal to ictal states.

Predictive factors of hydrocephalus development in pediatric patients undergoing hemispherectomy for intractable epilepsy.

OBJECTIVE: Hemispherectomy surgery is an effective procedure for pediatric patients with intractable hemispheric epilepsy. Hydrocephalus is a well-documented complication of hemispherectomy contributing substantially to patient morbidity. Despite some clinical and operative factors demonstrating an association with hydrocephalus development, the true mechanism of disease is incompletely understood. The aim of this study was to investigate a range of clinical and surgical factors that may contribute to hydrocephalus to enhance understanding of the development of this complication and to aid the clinician in optimizing peri- and postoperative surgical management. METHODS: A retrospective chart review was conducted on all pediatric patients younger than 21 years who underwent hemispherectomy surgery at the Cleveland Clinic between 2002 and 2016. Data collected for each patient included general demographic information, neurological and surgical history, surgical technique, pathological analysis, presence and duration of perioperative CSF diversion, CSF laboratory values obtained while an external ventricular drain (EVD) was in place, length of hospital stay, postoperative aseptic meningitis, and in-hospital surgical complications (including perioperative stroke, hematoma formation, wound breakdown, and/or infection). Outcomes data included hemispherectomy revision and Engel grade at last follow-up (based on the Engel Epilepsy Surgery Outcome Scale). RESULTS: Data were collected for 204 pediatric patients who underwent hemispherectomy at the authors' institution. Twenty-eight patients (14%) developed hydrocephalus requiring CSF diversion. Of these 28 patients, 13 patients (46%) presented with hydrocephalus during the postoperative period (within 90 days), while the remaining 15 patients (54%) presented later (beyond 90 days after surgery). Multivariate analysis revealed postoperative aseptic meningitis (OR 7.0, p = 0.001), anatomical hemispherectomy surgical technique (OR 16.3 for functional/disconnective hemispherectomy and OR 7.6 for modified anatomical, p = 0.004), male sex (OR 4.2, p = 0.012), and surgical complications (OR 3.8, p = 0.031) were associated with an increased risk of hydrocephalus development, while seizure freedom (OR 0.3, p = 0.038) was associated with a decreased risk of hydrocephalus. CONCLUSIONS: Hydrocephalus remains a prominent complication following hemispherectomy, presenting both in the postoperative period and months to years after surgery. Aseptic meningitis, anatomical hemispherectomy surgical technique, male sex, and surgical complications show an association with an increased rate of hydrocephalus development while seizure freedom postsurgery is associated with a decreased risk of subsequent hydrocephalus. These findings speak to the multifactorial nature of hydrocephalus development and should be considered in the management of pediatric patients undergoing hemispherectomy for medically intractable epilepsy.

Validation and Safety Profile of a Novel, Noninvasive Fiducial Attachment for Stereotactic Robotic-Guided Stereoelectroencephalography: A Case Series.

BACKGROUND AND OBJECTIVES: We developed, tested, and validated a novel, noninvasive, Leksell G frame-based fiducial attachment, for use in stereotactic registration for stereoelectroencephalography (sEEG). Use of the device increased the number of fixed reference points available for registration, while obviating the need for additional scalp incisions. We report here on our experience and safety profile of using the device. METHODS: We collected registration data using the fiducial device across 25 adult and pediatric patients with epilepsy consecutively undergoing robotic-guided sEEG for invasive epilepsy monitoring, treated between May 2022 and July 2023. ROSA One Brain was used for trajectory planning and electrode implantation. Postoperative clinical and radiographic data were computed and quantified, including mean registration error for all patients. Entry point, target point (TP), and angular errors were measured. Descriptive statistics and correlation coefficients for error were calculated. RESULTS: Twenty-five patients underwent robotic-guided sEEG implantation (11 patients, bilateral; 10 patients, left unilateral; 4 patients, right). The mean number of electrodes per patient was 18 ± 3. The average mean registration error was 0.77 ± 0.11 mm. All patients were implanted with Ad-Tech depth electrodes. No clinically relevant complications were reported. Analysis of trajectory error was performed on 446 electrodes. The median entry point error was 1.03 mm (IQR 0.69-1.54). The median TP error was 2.26 mm (IQR 1.63-2.93). The mean angular error was 0.03 radians (IQR 0.02-0.05). There was no significant correlation between root mean square error and lead error. Root mean square error did not appreciably change over time, nor were there any significant changes in average angular, entry point, or TP error metrics. CONCLUSION: A novel, noninvasive, Leksell G frame-based fiducial attachment was developed, tested, and validated, facilitating O-arm-based stereotactic registration for sEEG. This simple innovation maintained an excellent accuracy and safety profile for sEEG procedures in epilepsy patients, with the added advantages of providing additional reference points for stereotactic registration, without requiring additional scalp incisions.

Radiofrequency ablation during stereoelectroencephalography: from diagnostic tool to therapeutic intervention. Illustrative case.

BACKGROUND: Radiofrequency thermocoagulation (RFTC) during intracranial stereoelectroencephalography (sEEG) was first described as a safe technique for creating lesions of epileptic foci in 2004. Since that time, the method has been applied as a diagnostic and/or palliative intervention. Although widely practiced in European epilepsy surgical programs, the technique has not been popularized in the United States given the lack of Food and Drug Administration (FDA)-approved technologies permitting safe usage of in situ sEEG electrodes for this purpose. OBSERVATIONS: The authors present a case report of a young female patient with refractory left neocortical temporal lobe epilepsy undergoing sEEG electrode implantation, who underwent sEEG-guided RFTC via a stereotactic temperature-sensing pallidotomy probe. Although used as a diagnostic step in her workup, the patient has remained seizure-free for nearly 18 months. LESSONS: The use of in situ sEEG electrodes for RFTC remains limited in the United States. In this context, this case highlights a safe alternative and temporizing approach to performing diagnostic sEEG-guided RFTC, using a temperature-sensing pallidotomy probe to create small, precise stereotactic lesions. The authors caution careful consideration of this technique as a temporary work-around solution while also highlighting the rising need for new FDA-approved technologies for safe RFTC through in situ temperature-sensing sEEG electrodes.

Systematic Review of Enhanced Recovery After Surgery in Patients Undergoing Cranial Surgery.

BACKGROUND: Enhanced Recovery after Surgery (ERAS) pathways are increasingly being integrated in neurosurgical patient management. The full extent of ERAS in cranial surgery is not well studied. We performed a systematic review examining ERAS in cranial surgery patients to 1) identify the extent to which ERAS is integrated in cranial neurosurgical procedures and 2) assess effectiveness of ERAS interventions for patients undergoing these procedures. METHODS: A systematic review of MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, PsychInfo, and Google Scholar was conducted according to PRISMA guidelines (CRD42020197187). Studies eligible for inclusion assessed patients undergoing any cranial surgical procedure using an ERAS or ERAS-like pathway, defined by ≥2 ERAS protocol elements per the ERAS Society's RECOvER Checklist and the recommendations of Hagan et al. 2016 (not including patient education, criteria for discharge, or tracking of postdischarge outcomes). RESULTS: Nine studies were included in qualitative synthesis, 2 of which were randomized controlled trials. All studies showed a moderate risk of bias. The most common ERAS elements used were screening and/or optimization and formal discharge criteria. The least common ERAS elements used were fasting/carbohydrate loading and antithrombotic prophylaxis. Complication rates were similar in studies comparing ERAS with non-ERAS groups. ERAS interventions were associated with reduced length of stay, with comparable and/or improved patient satisfaction. CONCLUSIONS: ERAS is a safe and potentially favorable perioperative pathway for select patients undergoing cranial surgery. Future studies of ERAS in cranial surgery patients should emphasize postoperative optimizations and patient-reported outcome measures as key features.

Vasospasm following low-velocity penetrating pediatric intracranial trauma.

BACKGROUND: BB guns or non-powder guns created in the modern era are able to reach exceedingly fast velocities as a result of advances in compressed-gas technology. While missile penetrating trauma has been well documented in neurosurgical literature, penetrating intracranial injury secondary to non-powder guns, along with their associated complications and treatments, is not well described, and even less so in the pediatric population. CASE PRESENTATION: Here, we describe an unusual case of a 6-year-old Indigenous child who was accidentally shot with a BB gun to the head. He subsequently developed delayed acute right-sided weakness due to symptomatic vasospasm. His symptoms resolved following hypertensive therapy, balloon angioplasty intervention, and intra-arterial milrinone therapy. CONCLUSIONS: This case highlights the unique complication of delayed symptomatic vasospasm in a child following a non-missile intracranial penetrating injury. Intracranial vasospasm needs to be considered in the presence of delayed neurological deficit given its potential reversibility. This case also emphasizes the importance of gun safety and education when handling and storing these potential weapons around children.

Sleep-wake states change the interictal localization of candidate epileptic source generators.

STUDY OBJECTIVES: To compare estimated epileptic source localizations from 5 sleep-wake states (SWS): wakefulness (W), rapid eye movement sleep (REM), and non-REM 1-3. METHODS: Electrical source localization (sLORETA) of interictal spikes from different SWS on surface EEG from the epilepsy monitoring unit at spike peak and take-off, with results mapped to individual brain models for 75% of patients. Concordance was defined as source localization voxels shared between 2 and 5 SWS, and discordance as those unique to 1 SWS against 1-4 other SWS. RESULTS: 563 spikes from 16 prospectively recruited focal epilepsy patients across 161 day-nights. SWS exerted significant differences at spike peak but not take-off. Source localization size did not vary between SWS. REM localizations were smaller in multifocal than unifocal patients (28.8% vs. 54.4%, p = .0091). All five SWS contributed about 45% of their localizations to converge onto 17.0 ± 15.5% voxels. Against any one other SWS, REM was least concordant (54.4% vs. 66.9%, p = .0006) and most discordant (39.3% vs. 29.6%, p = .0008). REM also yielded the most unique localizations (20.0% vs. 8.6%, p = .0059). CONCLUSIONS: REM was best suited to identify candidate epileptic sources. sLORETA proposes a model in which an "omni-concordant core" of source localizations shared by all five SWS is surrounded by a "penumbra" of source localizations shared by some but not all SWS. Uniquely, REM spares this core to "move" source voxels from the penumbra to unique cortex not localized by other SWS. This may reflect differential intra-spike propagation in REM, which may account for its reported superior localizing abilities.