Atlantoaxial facet fixation using cervical facet cage: technical case report and review of the literature.

In 1994, the use of interfacet spacer placement was for joint distraction, reduction, and fusion to supplement atlantoaxial or occipitocervical fixation. Here, we present a unique case of bilateral atlantoaxial interfacet fixation using cervical facet cages (CFC) in a pediatric patient with basilar invagination. In addition, we review the literature on atlantoaxial facet fixation. We present a 12-year-old boy with Wiedemann-Steiner syndrome who presented with multiple episodes of sudden neck jerking, described as in response to a sensation of being shocked, and guarding against neck motion, found to have basilar invagination with cervicomedullary compression. He underwent an occiput to C3 fusion with C1-C2 CFC fixation. We also conducted a literature review identifying all publications using the following keywords: "C1" AND "C2" OR "atlantoaxial" AND "facet spacer" OR "DTRAX." The patient demonstrated postoperative radiographic reduction of his basilar invagination from 6.4 to 4.1 mm of superior displacement above the McRae line. There was a 4.5 mm decrease in the atlantodental interval secondary to decreased dens retroflexion. His postoperative course was complicated by worsening of his existing dysphagia but was otherwise unremarkable. His neck symptoms completely resolved. We illustrate the safe use of CFC for atlantoaxial facet distraction, reduction, and instrumented fixation in a pediatric patient with basilar invagination. Review of the literature demonstrates that numerous materials can be safely placed as a C1-C2 interfacet spacer including bone grafts, titanium spacers, and anterior cervical discectomy and fusion cages. We argue that CFC may be included in this arsenal even in pediatric patients.

Hemimegalencephaly: A Systematic Comparison of Functional and Anatomic Hemispherectomy for Drug-Resistant Epilepsy.

BACKGROUND AND OBJECTIVES: Hemimegalencephaly (HME) is a rare diffuse malformation of cortical development characterized by unihemispheric hypertrophy, drug-resistant epilepsy (DRE), hemiparesis, and developmental delay. Definitive treatment for HME-related DRE is hemispheric surgery through either anatomic (AH) or functional hemispherectomy (FH). This individual patient data meta-analysis assessed seizure outcomes of AH and FH for HME with pharmacoresistant epilepsy, predictors of Engel I, and efficacy of different FH approaches. METHODS: PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature were searched from inception to Jan 13th, 2023, for primary literature reporting seizure outcomes in >3 patients with HME receiving AH or FH. Demographics, neurophysiology findings, and Engel outcome at the last follow-up were extracted. Postsurgical seizure outcomes were compared through 2-tailed t -test and Fisher exact test. Univariate and multivariate Cox regression analyses were performed to identify independent predictors of Engel I outcome. RESULTS: Data from 145 patients were extracted from 26 studies, of which 89 underwent FH (22 vertical, 33 lateral), 47 underwent AH, and 9 received an unspecified hemispherectomy with a median last follow-up of 44.0 months (FH cohort) and 45.0 months (AH cohort). Cohorts were similar in preoperative characteristics and at the last follow-up; 77% (n = 66) of the FH cohort and 81% (n = 38) and of the AH cohort were Engel I. On multivariate analysis, only the presence of bilateral ictal electroencephalography abnormalities (hazard ratio = 11.5; P = .002) was significantly associated with faster time-to-seizure recurrence. A number-needed-to-treat analysis to prevent 1 additional case of posthemispherectomy hydrocephalus reveals that FH, compared with AH, was 3. There was no statistical significance for any differences in time-to-seizure recurrence between lateral and vertical FH approaches (hazard ratio = 2.59; P = .101). CONCLUSION: We show that hemispheric surgery is a highly effective treatment for HME-related DRE. Unilateral ictal electroencephalography changes and using the FH approach as initial surgical management may result in better outcomes due to significantly lower posthemispherectomy hydrocephalus probability. However, larger HME registries are needed to further delineate the predictors of seizure outcomes.

Comparison of magnetic resonance-guided laser interstitial thermal therapy corpus callosum ablation to open microsurgical corpus callosotomy: A single-center retrospective cohort study.

OBJECTIVE: Corpus callosotomy (CC) is an important treatment for atonic seizures in patients with generalized or multifocal drug-resistant epilepsy (DRE). Traditionally, CC is performed via an open microsurgical approach, but more recently, MR-guided stereotactic laser interstitial thermal therapy (LITT) corpus callosum ablation (CCA) has been developed to leverage the safety and minimally invasive nature of LITT. Given the recent adoption of CCA at select centers, how CCA compares to CC is unknown. We aim to compare the clinical seizure outcomes of CCA and CC after extended follow-up. METHODS: We performed a retrospective cohort study to compare the effectiveness and safety of CC to CCA from 1994 to 2022. The primary outcome was a 50% reduction in target seizure. Secondary outcome measures were postoperative length of stay, adverse events, and other effectiveness metrics. Comparative statistics were executed using Stata. Normality for continuous variables was assessed, and parametric statistics were utilized as needed. Frequency was compared with chi-squared or Fischer's exact tests, when applicable. RESULTS: Data from 47 operations performed on 36 patients were included in this study, of which 13 (36%) patients underwent 17 CCA. Patients who received CCA had similar rates of meaningful reduction (>50%) of atonic seizures as their CC counterparts (55% vs 70% P = 0.15). Patients undergoing CCA had significantly shorter hospitalizations than those receiving CC (2.5 vs 6.0 days P < 0.001). There was no significant difference in rates of postoperative complications between the groups, although the magnitude of the complication rates was lower in the CCA cohort (12% vs 28%). SIGNIFICANCE: This early experience suggests CCA has similar outcomes to traditional CC, albeit with a shorter hospital stay. However, future studies are necessary to investigate the noninferiority between these two approaches. Large multicenter studies are necessary to investigate differences in adverse events and whether these findings generalize across other centers.

Hemispheric epilepsy surgery for hemimegalencephaly: The UCLA experience.

OBJECTIVES: Hemimegalencephaly (HME) is a rare congenital brain malformation presenting predominantly with drug-resistant epilepsy. Hemispheric disconnective surgery is the mainstay of treatment; however, little is known about how postoperative outcomes compare across techniques. Thus we present the largest single-center cohort of patients with HME who underwent epilepsy surgery and characterize outcomes. METHODS: This observational study included patients with HME at University of California Los Angeles (UCLA) from 1984 to 2021. Patients were stratified by surgical intervention: anatomic hemispherectomy (AH), functional hemispherectomy (FH), or less-than-hemispheric resection (LTH). Seizure freedom, functional outcomes, and operative complications were compared across surgical approaches. Regression analysis identified clinical and intraoperative variables that predict seizure outcomes. RESULTS: Of 56 patients, 43 (77%) underwent FH, 8 (14%) underwent AH, 2 (4%) underwent LTH, 1 (2%) underwent unknown hemispherectomy type, and 2 (4%) were managed non-operatively. At median last follow-up of 55 months (interquartile range [IQR] 20-92 months), 24 patients (49%) were seizure-free, 17 (30%) required cerebrospinal fluid (CSF) shunting for hydrocephalus, 9 of 43 (21%) had severe developmental delay, 8 of 38 (21%) were non-verbal, and 15 of 38 (39%) were non-ambulatory. There was one (2%) intraoperative mortality due to exsanguination earlier in this cohort. Of 12 patients (29%) requiring revision surgery, 6 (50%) were seizure-free postoperatively. AH, compared to FH, was not associated with statistically significant improved seizure freedom (hazard ratio [HR] = .48, p = .328), although initial AH trended toward greater odds of seizure freedom (75% vs 46%, p = .272). Younger age at seizure onset (HR = .29, p = .029), lack of epilepsia partialis continua (EPC) (HR = .30, p = .022), and no contralateral seizures on electroencephalography (EEG) (HR = .33, p = .039) independently predicted longer duration of seizure freedom. SIGNIFICANCE: This study helps inform physicians and parents of children who are undergoing surgery for HME by demonstrating that earlier age at seizure onset, absence of EPC, and no contralateral EEG seizures were associated with longer postoperative seizure freedom. At our center, initial AH for HME may provide greater odds of seizure freedom with complications and functional outcomes comparable to those of FH.

Characterization of low-grade epilepsy-associated tumor from implanted stereoelectroencephalography electrodes.

Low-grade epilepsy-associated tumors (LEATs) are a common cause of drug-resistant epilepsy in children. Herein, we demonstrate the feasibility of using tumor tissue derived from stereoelectroencephalography (sEEG) electrodes upon removal to molecularly characterize tumors and aid in diagnosis. An 18-year-old male with focal epilepsy and MRI suggestive of a dysembryoplastic neuroepithelial tumor (DNET) in the left posterior temporal lobe underwent implantation of seven peri-tumoral sEEG electrodes for peri-operative language mapping and demarcation of the peri-tumoral ictal zone prior to DNET resection. Using electrodes that passed through tumor tissue, we show successful isolation of tumor DNA and subsequent analysis using standard methods for tumor classification by DNA, including Glioseq targeted sequencing and DNA methylation array analysis. This study provides preliminary evidence for the feasibility of molecular diagnosis of LEATs or other lesions using a minimally invasive method with microscopic tissue volumes. The implications of sEEG electrodes in tumor characterization are broad but would aid in diagnosis and subsequent targeted therapeutic strategies.

Somatic Mosaicism in PIK3CA Variant Correlates With Stereoelectroencephalography-Derived Electrophysiology.

Objectives: Brain-limited pathogenic somatic variants are associated with focal pediatric epilepsy, but reliance on resected brain tissue samples has limited our ability to correlate epileptiform activity with abnormal molecular pathology. We aimed to identify the pathogenic variant and map variant allele fractions (VAFs) across an abnormal region of epileptogenic brain in a patient who underwent stereoelectroencephalography (sEEG) and subsequent motor-sparing left frontal disconnection. Methods: We extracted genomic DNA from peripheral blood, brain tissue resected from peri-sEEG electrode regions, and microbulk brain tissue adherent to sEEG electrodes. Samples were mapped based on an anatomic relationship with the presumed seizure onset zone (SOZ). We performed deep panel sequencing of amplified and unamplified DNA to identify pathogenic variants with subsequent orthogonal validation. Results: We detect a pathogenic somatic PIK3CA variant, c.1624G>A (p.E542K), in the brain tissue samples, with VAF inversely correlated with distance from the SOZ. In addition, we identify this variant in amplified electrode-derived samples, albeit with lower VAFs. Discussion: We demonstrate regional mosaicism across epileptogenic tissue, suggesting a correlation between variant burden and SOZ. We also validate a pathogenic variant from individual amplified sEEG electrode-derived brain specimens, although further optimization of techniques is required.

Infant Rudimentary Meningocele with Tethering of the Cervical Cord: A Case Report.

Rudimentary meningoceles of the spine with dural extension are very rare and warrant surgical excision to prevent infection and long-term neurological deficits in pediatric patients. We present the case of a 5-month-old infant with a tethered spinal cord secondary to a rudimentary meningocele. The patient presented shortly after birth with a midline cervical dimple that was evaluated for a suspected dermal sinus tract. Magnetic resonance imaging scan of the spine showed a sinus tract with intradural extension to C2-3 and external opening at the level of spinous process C5. En bloc surgical excision and spinal cord release were successfully performed. Histological analysis of the specimen confirmed the presence of two blunt sinus tracts and staining was consistent with a rudimentary meningocele. Intradural rudimentary meningoceles in infants can successfully be managed with surgical intervention. Surgery is indicated to prevent future motor complications from spinal cord tethering and neoplastic growth from the rudimentary meningocele.

Focal drug-resistant temporal lobe epilepsy associated with an ipsilateral anterior choroidal artery aneurysm: illustrative case.

BACKGROUND: The occurrence of both an intracranial aneurysm and epilepsy, especially drug-resistant epilepsy (DRE), is rare. Although the overall incidence of aneurysms associated with DRE is unclear, it is thought to be particularly infrequent in the pediatric population. Surgical ligation of the offending aneurysm has been reported in conjunction with resolving seizure activity, although few cases have cited a combined approach of aneurysm ligation and resection of an epileptogenic focus. OBSERVATIONS: We present the case of a 14-year-old female patient with drug-resistant temporal lobe epilepsy and an ipsilateral supraclinoid internal carotid artery aneurysm. Seizure semiology, electroencephalography monitoring, and magnetic resonance imaging all indicated a left temporal epileptogenic focus, in addition to an incidental aneurysm. The authors recommended a combined surgery involving resection of the temporal lesion and surgical clip ligation of the aneurysm. Near-total resection and successful ligation were achieved, and the patient has remained seizure free since surgery at 1 year postoperatively. LESSONS: In patients with focal DRE and an adjacent intracranial aneurysm, a combined surgical approach involving both resection and surgical ligation can be used. Several surgical timing and neuroanesthetic considerations should be made to ensure the overall safety and efficacy of this procedure.

Characteristics of ictal thalamic EEG in pediatric-onset neocortical focal epilepsy.

Objective: To characterize ictal EEG change in the centromedian (CM) and anterior nucleus (AN) of the thalamus, using stereoelectroencephalography (SEEG) recordings. Methods: Forty habitual seizures were analyzed in nine patients with pediatric-onset neocortical drug-resistant epilepsy who underwent SEEG (age 2-25 y) with thalamic coverage. Both visual and quantitative analysis was used to evaluate ictal EEG signal in the cortex and thalamus. The amplitude and cortico-thalamic latencies of broadband frequencies at ictal onset were measured. Results: Visual analysis demonstrated consistent detection of ictal EEG changes in both the CM nucleus and AN nucleus with latency to thalamic ictal EEG changes of less than 400ms in 95% of seizures, with low-voltage fast activity being the most common ictal pattern. Quantitative broadband amplitude analysis showed consistent power changes across the frequency bands, corresponding to ictal EEG onset, while while ictal EEG latency was variable from -18.0 seconds to 13.2 seconds. There was no significant difference between detection of CM and AN ictal activity on visual or amplitude analysis. Four patients with subsequent thalamic responsive neurostimulation (RNS) demonstrated ictal EEG changes consistent with SEEG findings. Conclusions: Ictal EEG changes were consistently seen at the CM and AN of the thalamus during neocortical seizures. Significance: It may be feasible to use a closed-loop system in the thalamus to detect and modulate seizure activity for neocortical epilepsy.

Utility of minimally invasive endoscopic skull base approaches for the treatment of drug-resistant mesial temporal lobe epilepsy: a review of current techniques and trends.

Mesial temporal lobe epilepsy (mTLE) is an important cause of drug-resistant epilepsy (DRE) in adults and children. Traditionally, the surgical option of choice for mTLE includes a frontotemporal craniotomy and open resection of the anterior temporal cortex and mesial temporal structures. Although this technique is effective and durable, the neuropsychological morbidity resulting from temporal neocortical resections has resulted in the investigation of alternative approaches to resect the mesial temporal structures to achieve seizure freedom while minimizing postoperative cognitive deficits. Outcomes supporting the use of selective temporal resections have resulted in alternative approaches to directly access the mesial temporal structures via endoscopic approaches whose direct trajectory to the epileptogenic zone minimizes retraction, resection, and manipulation of surrounding cortex. The authors reviewed the utility of the endoscopic transmaxillary, endoscopic endonasal, endoscopic transorbital, and endoscopic supracerebellar transtentorial approaches for the treatment of drug-resistant mesial temporal lobe epilepsy. First, a review of the literature demonstrated the anatomical feasibility of each approach, including the limits of exposure provided by each trajectory. Next, clinical data assessing the safety and effectiveness of these techniques in the treatment of DRE were analyzed. An outline of the surgical techniques is provided to highlight the technical nuances of each approach. The direct access to mesial temporal structures and avoidance of lateral temporal manipulation makes endoscopic approaches promising alternatives to traditional methods for the treatment of DRE arising from the temporal pole and mesial temporal lobe. A dearth of literature outlining clinical outcomes, a need for qualified cosurgeons, and a lack of experience with endoscopic approaches remain major barriers to widespread application of the aforementioned techniques. Future studies are warranted to define the utility of these approaches moving forward.

Comparison of Hemispheric Surgery Techniques for Pediatric Drug-Resistant Epilepsy: An Individual Patient Data Meta-analysis.

BACKGROUND AND OBJECTIVES: Hemispheric surgery effectively treats unihemispheric pediatric drug-resistant epilepsy (DRE) by resecting and/or disconnecting the epileptic hemisphere. Modifications to the original anatomic hemispherectomy have generated multiple functionally equivalent, disconnective techniques for performing hemispheric surgery, termed functional hemispherotomy. While a myriad of hemispherotomy variants exist, all of them can be categorized according to the anatomic plane they are performed in, which includes vertical approaches at or near the interhemispheric fissure and lateral approaches at or near the Sylvian fissure. This meta-analysis of individual patient data (IPD) aimed to compare seizure outcomes and complications between the hemispherotomy approaches to better characterize their relative efficacy and safety in the modern neurosurgical treatment of pediatric DRE, given emerging evidence that outcomes may differ between them. METHODS: CINAHL, Embase, PubMed, and Web of Science were searched from inception to September 9, 2020, for studies reporting IPD from pediatric patients with DRE who underwent hemispheric surgery. Outcomes of interest were seizure freedom at last follow-up, time-to-seizure recurrence, and complications including hydrocephalus, infection, and mortality. The χ2 test compared the frequency of seizure freedom and complications. Multivariable mixed-effects Cox regression controlling for predictors of seizure outcome was performed on propensity score-matched patients to compare time-to-seizure recurrence between approaches. Kaplan-Meier curves were made to visualize differences in time-to-seizure recurrence. RESULTS: Fifty-five studies reporting on 686 unique pediatric patients treated with hemispheric surgery were included for meta-analysis. Among the hemispherotomy subgroup, vertical approaches resulted in a greater proportion of seizure free patients (81.2% vs 70.7%, p = 0.014) than lateral approaches. While there were no differences in complications, lateral hemispherotomy had higher rates of revision hemispheric surgery due to incomplete disconnection and/or recurrent seizures than vertical hemispherotomy (16.3% vs 1.2%, p < 0.001). After propensity score matching, vertical hemispherotomy approaches independently conferred longer time-to-seizure recurrence than lateral hemispherotomy approaches (hazard ratio 0.44, 95% CI 0.19-0.98). DISCUSSION: Among functional hemispherotomy techniques, vertical hemispherotomy approaches confer more durable seizure freedom than lateral approaches without compromising safety. Future prospective studies are required to definitively determine whether vertical approaches are indeed superior and how it should influence clinical guidelines for performing hemispheric surgery.

Contribution of Somatic Ras/Raf/Mitogen-Activated Protein Kinase Variants in the Hippocampus in Drug-Resistant Mesial Temporal Lobe Epilepsy.

Importance: Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy subtype and is often refractory to antiseizure medications. While most patients with MTLE do not have pathogenic germline genetic variants, the contribution of postzygotic (ie, somatic) variants in the brain is unknown. Objective: To test the association between pathogenic somatic variants in the hippocampus and MTLE. Design, Setting, and Participants: This case-control genetic association study analyzed the DNA derived from hippocampal tissue of neurosurgically treated patients with MTLE and age-matched and sex-matched neurotypical controls. Participants treated at level 4 epilepsy centers were enrolled from 1988 through 2019, and clinical data were collected retrospectively. Whole-exome and gene-panel sequencing (each genomic region sequenced more than 500 times on average) were used to identify candidate pathogenic somatic variants. A subset of novel variants was functionally evaluated using cellular and molecular assays. Patients with nonlesional and lesional (mesial temporal sclerosis, focal cortical dysplasia, and low-grade epilepsy-associated tumors) drug-resistant MTLE who underwent anterior medial temporal lobectomy were eligible. All patients with available frozen tissue and appropriate consents were included. Control brain tissue was obtained from neurotypical donors at brain banks. Data were analyzed from June 2020 to August 2022. Exposures: Drug-resistant MTLE. Main Outcomes and Measures: Presence and abundance of pathogenic somatic variants in the hippocampus vs the unaffected temporal neocortex. Results: Of 105 included patients with MTLE, 53 (50.5%) were female, and the median (IQR) age was 32 (26-44) years; of 30 neurotypical controls, 11 (36.7%) were female, and the median (IQR) age was 37 (18-53) years. Eleven pathogenic somatic variants enriched in the hippocampus relative to the unaffected temporal neocortex (median [IQR] variant allele frequency, 1.92 [1.5-2.7] vs 0.3 [0-0.9]; P = .01) were detected in patients with MTLE but not in controls. Ten of these variants were in PTPN11, SOS1, KRAS, BRAF, and NF1, all predicted to constitutively activate Ras/Raf/mitogen-activated protein kinase (MAPK) signaling. Immunohistochemical studies of variant-positive hippocampal tissue demonstrated increased Erk1/2 phosphorylation, indicative of Ras/Raf/MAPK activation, predominantly in glial cells. Molecular assays showed abnormal liquid-liquid phase separation for the PTPN11 variants as a possible dominant gain-of-function mechanism. Conclusions and Relevance: Hippocampal somatic variants, particularly those activating Ras/Raf/MAPK signaling, may contribute to the pathogenesis of sporadic, drug-resistant MTLE. These findings may provide a novel genetic mechanism and highlight new therapeutic targets for this common indication for epilepsy surgery.

Preliminary Experience Suggests the Addition of Choroid Plexus Cauterization to Functional Hemispherectomy May Reduce Posthemispherectomy Hydrocephalus.

BACKGROUND: Cerebral hemispherectomy can effectively treat unihemispheric epilepsy. However, posthemispherectomy hydrocephalus (PHH), a serious life-long complication, remains prevalent, requiring careful considerations in technique selection and postoperative management. In 2016, we began incorporating open choroid plexus cauterization (CPC) into our institution's hemispherectomy procedure in an attempt to prevent PHH. OBJECTIVE: To determine whether routine CPC prevented PHH without exacerbating hemispherectomy efficacy or safety. METHODS: A retrospective review of consecutive patients who underwent hemispherectomy for intractable epilepsy between 2011 and 2021 was performed. Multivariate logistic regression was used to identify factors independently associated with PHH requiring cerebrospinal fluid (CSF) shunting. RESULTS: Sixty-eight patients were included in this study, of whom 26 (38.2%) underwent CPC. Fewer patients required CSF shunting in the CPC group (7.7% vs 28.7%, P = .033) and no patients who underwent de novo hemispherectomy with CPC developed PHH. Both cohorts experienced seizure freedom (65.4% vs 59.5%, P = .634) and postoperative complications, including infection (3.8% vs 2.4%, P = .728), hemorrhage (0.0% vs 2.4%, P = .428), and revision hemispherectomy (19.2% vs 14.3%, P = .591) at similar rates. Patients without CPC had greater odds of developing PHH requiring CSF shunting (odds ratio = 8.36, P = .026). The number needed to treat with CPC to prevent an additional case of PHH was 4.8, suggesting high effectiveness. CONCLUSION: Preventing PHH is critical. Our early experience demonstrated that routinely incorporating CPC into hemispherectomy effectively prevents PHH without causing additional complications, especially in first-time hemispherectomies. A multicenter randomized controlled trial with long-term follow-up is required to corroborate the findings of our single-institutional case series and determine whether greater adoption of this technique is justified.

Long-term outcomes of pediatric epilepsy surgery: Individual participant data and study level meta-analyses.

OBJECTIVE: Long-term seizure outcomes of pediatric epilepsy surgery are understudied. A systematic review and independent patient data meta-analysis was performed to study seizure outcomes ≥ 10 years following pediatric resective epilepsy surgery. METHODS: Electronic literature searches of PubMed, Web of Science, and CINAHL were conducted for relevant articles from inception to April 2020. The following search terms were used in various combinations: "pediatric", "child", "adolescent", "epilepsy", "resective", "surgery", "long-term", "longitudinal", "10 year". Two reviewers (W.B.H., T.B.C.) performed title, abstract, and full-text screening. All relevant perioperative factors reported that may be associated with long-term seizure outcomes were recorded at a study or individual participant level. The primary outcome was long-term (≥ 10 year) seizure freedom measured by the Engel Classification scale, and available data on functional outcomes were also reviewed. RESULTS: Twenty-five articles met criteria for inclusion in the study, which were analyzed for proportions of 10-year seizure freedom ranging from 57.6% at the study level to 64.8% at the individual patient level. At the study level, the proportion of patients remaining seizure free at least 10 years postoperatively (61.2%; 95% CI 52.5-69.3) was significantly less than at 1 year (74.2%; 95% CI 69.3-78.6; p = 0.008) but not at 2 years (67.9%; 95% CI 58.6-76.0) or 5 years (63.7%; 95% CI 55.4-71.2). No differences in long-term seizure freedom were detected by etiology or surgery type. At the individual patient level, univariate logistic regression analyses of all variables putatively associated with seizure freedom demonstrated that lobectomy (OR 0.280, 95% CI 0.117-0.651, p = 0.003) was associated with decreased long-term seizure freedom (41.9%) compared to lesionectomy (75.7%) and hemispherectomy (69.4%), which achieved similar results. CONCLUSION: Resective surgery is a durable and potentially curative treatment option for select pediatric patients with refractory epilepsy. On a group level, two-thirds of children have long-term seizure freedom ≥ 10 years after resective epilepsy surgery. Given the greatest rate of change occurs in the first 2 years, this may serve as the best short-term follow-up period to predict long-term outcome. Although lobectomy appears to be a strong predictor for lower likelihood of long-term seizure freedom, long-term prognostication on an individual patient level is still not possible. Uniform data reporting and prospective, multicenter studies collecting high quality, stratified (e.g., by etiology, surgery type) data over an extended postoperative interval are recommended to further examine the durability of resective surgery as a treatment for pediatric epilepsy.

Sensorimotor outcomes after resection for perirolandic drug-resistant epilepsy: a systematic review and individual patient data meta-analysis.

OBJECTIVE: The prevalence of long-term postoperative sensorimotor deficits in children undergoing perirolandic resective epilepsy surgery is unclear. The risk of developing these deficits must be weighed against the potential reduction in seizure frequency after surgery. In this study, the authors investigated the prevalence of sensorimotor deficits after resective surgery at ≥ 1 year postoperatively. METHODS: A systematic review and individual patient data meta-analysis was conducted using PubMed, Embase, and Scopus databases. Subgroups of patients were identified and categorized according to their outcomes as follows: group A patients were denoted as seizure free with no postoperative sensorimotor deficits; group B patients experienced seizure recurrence with no deficit; group C patients were seizure free with deficits; and group D patients were not seizure free and with deficits. Rates of sensory deficits were examined in patients undergoing postcentral gyrus resection, and rates of motor deficits were aggregated in patients undergoing precentral gyrus resection. RESULTS: Of 797 articles resulting from the database searches, 6 articles including 164 pediatric patients at a mean age of 7.7 ± 5.2 years with resection for drug-resistant perirolandic epilepsy were included in the study. Seizure freedom was observed in 118 (72.9%) patients at a mean follow-up of 3.4 ± 1.8 years. In total, 109 (66.5%) patients did not develop sensorimotor deficits at last follow-up, while 55 (33.5%) had permanent deficits. Ten (14.3%) of 70 patients with postcentral gyrus resection had permanent sensory deficits. Of the postcentral gyrus resection patients, 41 (58.6%) patients were included in group A, 19 (27.1%) in group B, 7 (10.0%) in group C, and 3 (4.3%) in group D. Forty (37.7%) of 106 patients with precentral resections had permanent motor deficits. Of the precentral gyrus resection patients, 50 (47.2%) patients were in group A, 16 (15.1%) in group B, 24 (22.6%) in group C, and 16 (15.1%) in group D. Patients without focal cortical dysplasia were more likely to have permanent motor deficits relative to those with focal cortical dysplasia in the precentral surgery cohort (p = 0.02). CONCLUSIONS: In total, 58.6% of patients were seizure free without deficit, 27.1% were not seizure free and without deficit, 10.0% were seizure free but with deficit, and 4.3% were not seizure free and with deficit. Future studies with functional and quality-of-life data, particularly for patients who experience seizure recurrence with no deficits (as in group B in the present study) and those who are seizure free with deficits (as in group C) after treatment, are necessary to guide surgical decision-making.

Midline Brain Shift After Hemispheric Surgery: Natural History, Clinical Significance, and Association With Cerebrospinal Fluid Diversion.

BACKGROUND: Hemispherectomy and its modern variants are effective surgical treatments for medically intractable unihemispheric epilepsy. Although some complications such as posthemispherectomy hydrocephalus are well documented, midline brain shift (MLBS) after hemispheric surgery has only been described anecdotally and never formally studied. OBJECTIVE: To assess the natural history and clinical relevance of MLBS and determine whether cerebrospinal fluid (CSF) shunting of the ipsilateral surgical cavity exacerbates MLBS posthemispheric surgery. METHODS: A retrospective review of consecutive pediatric patients who underwent hemispheric surgery for intractable epilepsy and at least 6 months of follow-up at UCLA between 1994 and 2018 was performed. Patients were grouped by MLBS severity, shunt placement, valve type, and valve opening pressure (VOP). MLBS was evaluated using the paired samples t-test and analysis of covariance adjusting for follow-up time and baseline postoperative MLBS. RESULTS: Seventy patients were analyzed, of which 23 (33%) required CSF shunt placement in the ipsilateral surgical cavity for posthemispherectomy hydrocephalus. MLBS increased between first and last follow-up for nonshunted (5.3 ± 4.9-9.7 ± 6.6 mm, P < .001) and shunted (6.6 ± 3.5-16.3 ± 9.4 mm, P < .001) patients. MLBS progression was greater in shunted patients (P = .001). Shunts with higher VOPs did not increase MLBS relative to nonshunted patients (P = .834), whereas MLBS increased with lower VOPs (P = .001). Severe MLBS was associated with debilitating headaches (P = .048). CONCLUSION: Patients undergoing hemispheric surgery often develop postoperative MLBS, ie, exacerbated by CSF shunting of the ipsilateral surgical cavity, specifically when using lower VOP settings. MLBS exacerbation may be related to overshunting. Severe MLBS is associated with debilitating headaches.

Customized polyetheretherketone (PEEK) implants are associated with similar hospital length of stay compared to autologous bone used in cranioplasty procedures.

OBJECTIVE: Cranioplasty is the surgical repair of cranial defects. Throughout its history, a number of different materials have been used, however, there is still no consensus on which material or method is best. The purpose of this study was to analyze the viability of polyetheretherketone (PEEK) cranioplasty to autologous cranioplasty modalities. METHODS: A single-institution retrospective analysis of patients undergoing cranioplasties was performed. Patients were divided to PEEK and autologous cranioplasty cohorts. Parameters of interest included patient demographics and perioperative outcomes. A p-value <0.05 was considered statistically significant. RESULTS: A total of 66 patients met the inclusion criteria (PEEK: 22, autologous: 44). There were 36 males (54.5%) and 30 females (45.5%). Mean age of the entire cohort was 51.7 years (range 19-85 years). Baseline demographics were similar in both cohorts as measured by the modified frailty index (mFI) (p = 0.67). Univariate analysis revealed a significantly longer hospital length of stay (LoS) associated with the autologous group (p = 0.02). However, multivariate analysis did not yield such an association (p = 0.06) after controlling for mFI. Although the individual postoperative complication rates were similar between the two cohorts, autologous cranioplasty was associated with a significantly higher rate of total postoperative complications (65.9% vs 36.4%, p = 0.02). CONCLUSION: Overall, PEEK biomaterials may offer a superior complication profile with similar hospital LoS compared to autologous bone implants used in cranioplasty. Future studies are warranted to validate our findings and further evaluate the utility of PEEK in cranioplasty.

Advances in the Treatment of Pediatric Brain Tumors.

Pediatric brain tumors are the most common solid malignancies in children. Advances in the treatment of pediatric brain tumors have come in the form of imaging, biopsy, surgical techniques, and molecular profiling. This has led the way for targeted therapies and immunotherapy to be assessed in clinical trials for the most common types of pediatric brain tumors. Here we review the latest efforts and challenges in targeted molecular therapy, immunotherapy, and newer modalities such as laser interstitial thermal therapy.

Real-World Preliminary Experience With Responsive Neurostimulation in Pediatric Epilepsy: A Multicenter Retrospective Observational Study.

BACKGROUND: Despite the well-documented utility of responsive neurostimulation (RNS, NeuroPace) in adult epilepsy patients, literature on the use of RNS in children is limited. OBJECTIVE: To determine the real-world efficacy and safety of RNS in pediatric epilepsy patients. METHODS: Patients with childhood-onset drug-resistant epilepsy treated with RNS were retrospectively identified at 5 pediatric centers. Reduction of disabling seizures and complications were evaluated for children (<18 yr) and young adults (>18 yr) and compared with prior literature pertaining to adult patients. RESULTS: Of 35 patients identified, 17 were <18 yr at the time of RNS implantation, including a 3-yr-old patient. Four patients (11%) had concurrent resection. Three complications, requiring additional surgical interventions, were noted in young adults (2 infections [6%] and 1 lead fracture [3%]). No complications were noted in children. Among the 32 patients with continued therapy, 2 (6%) achieved seizure freedom, 4 (13%) achieved ≥90% seizure reduction, 13 (41%) had ≥50% reduction, 8 (25%) had <50% reduction, and 5 (16%) experienced no improvement. The average follow-up duration was 1.7 yr (median 1.8 yr, range 0.3-4.8 yr). There was no statistically significant difference for seizure reduction and complications between children and young adults in our cohort or between our cohort and the adult literature. CONCLUSION: These preliminary data suggest that RNS is well tolerated and an effective off-label surgical treatment of drug-resistant epilepsy in carefully selected pediatric patients as young as 3 yr of age. Data regarding long-term efficacy and safety in children will be critical to optimize patient selection.

Systematic Review of Serum Biomarkers in Traumatic Brain Injury.

Traumatic brain injury (TBI) is responsible for the majority of trauma-related deaths and is a leading cause of disability. It is characterized by an inflammatory process involved in the progression of secondary brain injury. TBI is measured by the Glasgow Coma Scale (GCS) with scores ranging from 15-3, demonstrating mild to severe brain injury. Apart from this clinical assessment of TBI, compendiums of literature have been published on TBI-related serum markers.Herein we create a comprehensive appraisal of the most prominent serum biomarkers used in the assessment and care of TBI.The PubMed, Scopus, Cochrane, and Web of Science databases were queried with the terms "biomarker" and "traumatic brain injury" as search terms with only full-text, English articles within the past 10 years selected. Non-human studies were excluded, and only adult patients fell within the purview of this analysis. A total of 528 articles were analyzed in the initial search with 289 selected for screening. A further 152 were excluded for primary screening. Of the remaining 137, 54 were included in the final analysis. Serum biomarkers were listed into the following broad categories for ease of discussion: immune markers and markers of inflammation, hormones as biomarkers, coagulation and vasculature, genetic polymorphisms, antioxidants and oxidative stress, apoptosis and degradation pathways, and protein markers. Glial fibrillary acidic protein(GFAP), S100, and neurons specific enolase (NSE) were the most prominent and frequently cited markers. Amongst these three, no single serum biomarker demonstrated neither superior sensitivity nor specificity compared to the other two, therefore noninvasive panels should incorporate these three serum biomarkers to retain sensitivity and maximize specificity for TBI.