Harold Westley Phillips

All Publications

• Somatic Mosaicism inPIK3CAVariant Correlates With Stereoelectroencephalography-Derived Electrophysiology. Neurology. Genetics Phillips, H. W., D'Gama, A. M., Wang, Y., Chahine, Y., Chiu, M., Swanson, A. C., Ahtam, B., Bolton, J. B., Madsen, J. R., Lee, E. A., Prabhu, S. P., Lidov, H. G., Papadakis, J., Huang, A. Y., Poduri, A., Stone, S. S., Walsh, C. A. 2024; 10 (1): e200117

  Abstract

  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.

  View details for DOI 10.1212/NXG.0000000000200117

  View details for PubMedID 38149038

• Hemispheric Epilepsy Surgery for Hemimegalencephaly: The UCLA Experience. Epilepsia Goel, K., Phillips, H. W., Chen, J., Ngo, J., Edmonds, B., Ha, P. X., Wang, A., Weil, A., Russell, B. E., Salamon, N., Nariai, H., Fallah, A. 2023

  Abstract

  OBJECTIVES: Hemimegalencephaly (HME) is a rare congenital brain malformation predominantly presenting 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 UCLA from 1984-2021. 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 (IQR:20-92) months, 24 (49%) patients were seizure-free, 17 (30%) required CSF-shunting for hydrocephalus, 9/43 (21%) had severe developmental delay, 8/38 (21%) were non-verbal, and 15/38 (39%) were non-ambulatory. There was 1 (2%) intraoperative mortality due to exsanguination earlier in this cohort. Of 12 (29%) requiring revision surgery, 6 (50%) were seizure-free postoperatively. AH, compared to FH, was not associated with improved seizure freedom (HR=0.48, p=0.328) and initial AH trended towards greater odds of seizure freedom (75% vs 46%, p=0.272). Younger age at onset (HR=0.29, p=0.029), lack of epilepsia continua partialis (EPC) (HR=0.30, p=0.022), and no contralateral seizures on EEG (HR=0.33, p=0.039) independently predicted longer duration of seizure-freedom.SIGNIFICANCE: This study helps inform physicians and parents of children 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 comparable complications and functional outcomes to FH.

  View details for DOI 10.1111/epi.17807

  View details for PubMedID 37873610

• Characterization of low-grade epilepsy associated tumor from implanted stereoelectroencephalography electrodes. Epilepsia open Gatesman, T. A., Hect, J. L., Phillips, H. W., Johnson, B. J., Wald, A. I., McClung, C., Nikiforova, M. N., Skaugen, J. M., Pollack, I. F., Abel, T. J., Agnihotri, S. 2023

  Abstract

  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.

  View details for DOI 10.1002/epi4.12840

  View details for PubMedID 37798921

• Comparison of magnetic resonance guided laser interstitial thermal therapy corpus callosum ablation (CCA) to open microsurgical corpus callosotomy (CC): A single center retrospective cohort study. Epilepsia open Phillips, H. W., Hect, J. L., Harford, E., Pan, E., Abel, T. J. 2023

  Abstract

  Corpus Callosotomy (CC) is an important treatment for atonic seizures in patients with generalized or multi-focal 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 clinical seizure outcomes of CCA to CC after extended follow-up.We performed a retrospective cohort study to compare the effectiveness and safety of CC to CCA from 1994-2022. The primary outcome was the difference between 50% reduction of 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 were assessed and parametric statistics were utilized as needed. Frequency was compared with chi-squared or Fischer's exact tests, when applicable.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 post-operative complications between the groups, although the magnitude of the complication rates was lower in the CCA cohort (12% vs 28%).This early experience suggests CCA has similar outcomes to traditional CC, albeit with shorter hospital length of stay. However, future studies are necessary to investigate non-inferiority between these two approaches. Large multi-center studies are necessary to investigate differences in adverse events and whether these findings generalize across other centers.

  View details for DOI 10.1002/epi4.12835

  View details for PubMedID 37766507

• Comparison of Hemispheric Surgery Techniques for Pediatric Drug-Resistant Epilepsy An Individual Patient Data Meta-analysis NEUROLOGY Chen, J., Harris, W. B., Wu, K. J., Phillips, H., Tseng, C., Weil, A. G., Fallah, A. 2023; 101 (4): E410-E424

  Abstract

  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.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.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).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.

  View details for DOI 10.1212/WNL.0000000000207425

  View details for Web of Science ID 001049388700018

  View details for PubMedID 37202158

  View details for PubMedCentralID PMC10435062

• Characteristics of ictal thalamic EEG in pediatric-onset neocortical focal epilepsy. medRxiv : the preprint server for health sciences Edmonds, B., Miyakoshi, M., Remore, L. G., Ahn, S., Phillips, H. W., Daida, A., Salamon, N., Bari, A., Sankar, R., Matsumoto, J. H., Fallah, A., Nariai, H. 2023

  Abstract

  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.

  View details for DOI 10.1101/2023.06.22.23291714

  View details for PubMedID 37425697

• Focal drug-resistant temporal lobe epilepsy associated with an ipsilateral anterior choroidal artery aneurysm: illustrative case. Journal of neurosurgery. Case lessons Phillips, H. W., Rangwala, S. D., Papadakis, J., Segar, D. J., Tsuboyama, M., Pinto, A. L., Harmon, J. P., Soriano, S. G., Munoz, C. J., Madsen, J. R., See, A. P., Stone, S. S. 2023; 5 (26)

  Abstract

  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.

  View details for DOI 10.3171/CASE23156

  View details for PubMedID 37399139

• 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. Journal of neurosurgery Phillips, H. W., Miller, T. A., Liu, H. Y., Abel, T. J., McDowell, M. M. 2023: 1-9

  Abstract

  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.

  View details for DOI 10.3171/2023.4.JNS221889

  View details for PubMedID 37347658

• Contribution of Somatic Ras/Raf/Mitogen-Activated Protein Kinase Variants in the Hippocampus in Drug-Resistant Mesial Temporal Lobe Epilepsy JAMA NEUROLOGY Khoshkhoo, S., Wang, Y., Chahine, Y., Erson-Omay, E., Robert, S. M., Kiziltug, E., Damisah, E. C., Nelson-Williams, C., Zhu, G., Kong, W., Huang, A., Stronge, E., Phillips, H., Chhouk, B. H., Bizzotto, S., Chen, M., Adikari, T. N., Ye, Z., Witkowski, T., Lai, D., Lee, N., Lokan, J., Scheffer, I. E., Berkovic, S. F., Haider, S., Hildebrand, M. S., Yang, E., Gunel, M., Lifton, R. P., Richardson, R., Bluemcke, I., Alexandrescu, S., Huttner, A., Heinzen, E. L., Zhu, J., Poduri, A., DeLanerolle, N., Spencer, D. D., Lee, E., Walsh, C. A., Kahle, K. T. 2023; 80 (6): 578-587

  Abstract

  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.To test the association between pathogenic somatic variants in the hippocampus and MTLE.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.Drug-resistant MTLE.Presence and abundance of pathogenic somatic variants in the hippocampus vs the unaffected temporal neocortex.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.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.

  View details for DOI 10.1001/jamaneurol.2023.0473

  View details for Web of Science ID 000998902600004

  View details for PubMedID 37126322

  View details for PubMedCentralID PMC10152377

• Preliminary Experience Suggests the Addition of Choroid Plexus Cauterization to Functional Hemispherectomy May Reduce Posthemispherectomy Hydrocephalus NEUROSURGERY Phillips, H., Chen, J., Tucker, A. M., Ding, K., Kashanian, A., Nagahama, Y., Mathern, G. W., Weil, A. G., Fallah, A. 2023; 92 (2): 300-307

  Abstract

  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.To determine whether routine CPC prevented PHH without exacerbating hemispherectomy efficacy or safety.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.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.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.

  View details for DOI 10.1227/neu.0000000000002193

  View details for Web of Science ID 000923062800026

  View details for PubMedID 36637266

  View details for PubMedCentralID PMC10553136

• Comprehensive multi-omic profiling of somatic mutations in malformations of cortical development NATURE GENETICS Chung, C., Yang, X., Bae, T., Vong, K., Mittal, S. H., Donkels, C., Westley Phillips, H., Li, Z., Marsh, A. L., Breuss, M., Ball, L., Garcia, C., George, R., Gu, J., Xu, M., Barrows, C., James, K., Stanley, V., Nidhiry, A., Khoury, S., Howe, G., Riley, E., Xu, X., Copeland, B., Wang, Y. G., Kim, S. L., Kang, H. W., Schulze-Bonhage, A., Haas, C., Urbach, H., Prinz, M., Limbrick, D. A., Gurnett, C., Smyth, M. C., Sattar, S. M., Nespeca, M. B., Gonda, D. V., Imai, K. Y., Takahashi, Y. E., Chen, H. B., Tsai, J., Conti, V., Guerrini, R., Devinsky, O., Silva, W., Machado, H. M., Mathern, G., Abyzov, A., Baldassari, S., Baulac, S., Gleeson, J. G., Focal Cort Dysplasia Neurogenet, Brain Somat Mosaicism Network 2023; 55 (2): 209-+

  Abstract

  Malformations of cortical development (MCD) are neurological conditions involving focal disruptions of cortical architecture and cellular organization that arise during embryogenesis, largely from somatic mosaic mutations, and cause intractable epilepsy. Identifying the genetic causes of MCD has been a challenge, as mutations remain at low allelic fractions in brain tissue resected to treat condition-related epilepsy. Here we report a genetic landscape from 283 brain resections, identifying 69 mutated genes through intensive profiling of somatic mutations, combining whole-exome and targeted-amplicon sequencing with functional validation including in utero electroporation of mice and single-nucleus RNA sequencing. Genotype-phenotype correlation analysis elucidated specific MCD gene sets associated with distinct pathophysiological and clinical phenotypes. The unique single-cell level spatiotemporal expression patterns of mutated genes in control and patient brains indicate critical roles in excitatory neurogenic pools during brain development and in promoting neuronal hyperexcitability after birth.

  View details for DOI 10.1038/s41588-022-01276-9

  View details for Web of Science ID 000914418600003

  View details for PubMedID 36635388

  View details for PubMedCentralID PMC9961399

• Sensorimotor outcomes after resection for perirolandic drug-resistant epilepsy: a systematic review and individual patient data meta-analysis JOURNAL OF NEUROSURGERY-PEDIATRICS Shlobin, N. A., Wang, A., Phillips, W., Yan, H., Ibrahim, G. M., Elkaim, L. M., Wang, S., Liu, X., Cai, L., Nguyen, D. K., Fallah, A., Weil, A. G. 2022; 30 (4): 410-427

  Abstract

  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.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.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).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.

  View details for DOI 10.3171/2022.6.PEDS22160

  View details for Web of Science ID 000892883400006

  View details for PubMedID 35932272

• Long-term outcomes of pediatric epilepsy surgery: Individual participant data and study level meta-analyses SEIZURE-EUROPEAN JOURNAL OF EPILEPSY Harris, W. B., Brunette-Clement, T., Wang, A., Phillips, H., von Der Brelie, C., Weil, A. G., Fallah, A. 2022; 101: 227-236

  Abstract

  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.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.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.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.

  View details for DOI 10.1016/j.seizure.2022.08.010

  View details for Web of Science ID 000869150100002

  View details for PubMedID 36108556

• Midline Brain Shift After Hemispheric Surgery: Natural History, Clinical Significance, and Association With Cerebrospinal Fluid Diversion OPERATIVE NEUROSURGERY Phillips, H., Maniquis, C. B., Chen, J., Duby, S. L., Nagahama, Y., Bergeron, D., Ibrahim, G. M., Weil, A. G., Fallah, A. 2022; 22 (5): 269-276

  Abstract

  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.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.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.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).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.

  View details for DOI 10.1227/ons.0000000000000134

  View details for Web of Science ID 000848310100023

  View details for PubMedID 35315814

  View details for PubMedCentralID PMC9514754

• Customized polyetheretherketone (PEEK) implants are associated with similar hospital length of stay compared to autologous bone used in cranioplasty procedures JOURNAL OF THE NEUROLOGICAL SCIENCES Mozaffari, K., Rana, S., Chow, A., Mahgerefteh, N., Duong, C., Sheppard, J. P., Phillips, H., Jarrahy, R., Yang, I. 2022; 434: 120169

  Abstract

  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.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.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).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.

  View details for DOI 10.1016/j.jns.2022.120169

  View details for Web of Science ID 000791273900012

  View details for PubMedID 35134672

• Superior Semicircular Canal Dehiscence Revision Surgery Outcomes: A Single Institution's Experience WORLD NEUROSURGERY Mozaffari, K., Ghodrati, F., Pradhan, A., Ng, E., Ding, K., Rana, S., Duong, C., Anderson, R. N., Enomoto, A., Sheppard, J. P., Sun, M. Z., Phillips, H., Yang, I., Gopen, Q. 2021; 156: E408-E414

  Abstract

  Superior semicircular canal dehiscence (SSCD) is an abnormality of the otic capsule, which normally overlies the superior semicircular canal. Surgical management is indicated in patients with persistent and debilitating symptoms. Given the complexity of the disease, there are patients who experience less favorable surgical outcomes and require revision surgery. The purpose of this study was to report to the rate of postoperative symptomatic improvement in patients who required revision surgery.A retrospective analysis of patients undergoing SSCD surgical repair at a single institution was performed. Information on patient demographics, primary and secondary surgical approaches, surgical outcomes, and follow-up length was collected.Seventeen patients underwent 20 revision surgeries. There were eleven (65%) females and six (35%) males. Mean age of the cohorts was 50 years (range 30-68 years), and mean follow-up length was 6.8 months (range 0.1-31.1 months). Cerebrospinal fluid leak was noted in 67% of cases. The greatest postoperative symptomatic resolution was reported in oscillopsia (100%), headache (100%), and internal sound amplification (71%), while the least postoperative symptomatic resolution was reported in tinnitus (42%), aural fullness (40%), and dizziness (29%).Revision surgery can provide symptomatic improvement in select SSCD patients; however, patients should be cautioned about the possibility of less favorable outcomes than in index surgery. Revision surgeries are associated with a considerably higher rate of perioperative cerebrospinal fluid leak.

  View details for DOI 10.1016/j.wneu.2021.09.083

  View details for Web of Science ID 000724953500009

  View details for PubMedID 34583007

• Real-World Preliminary Experience With Responsive Neurostimulation in Pediatric Epilepsy: A Multicenter Retrospective Observational Study. Neurosurgery Nagahama, Y., Zervos, T. M., Murata, K. K., Holman, L., Karsonovich, T., Parker, J. J., Chen, J., Phillips, H. W., Fajardo, M., Nariai, H., Hussain, S. A., Porter, B. E., Grant, G. A., Ragheb, J., Wang, S., O'Neill, B. R., Alexander, A. L., Bollo, R. J., Fallah, A. 2021

  Abstract

  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 <18yr 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.

  View details for DOI 10.1093/neuros/nyab343

  View details for PubMedID 34528103

• Systematic Review of Serum Biomarkers in Traumatic Brain Injury CUREUS JOURNAL OF MEDICAL SCIENCE Mozaffari, K., Dejam, D., Duong, C., Ding, K., French, A., Preet, E., Franks, A., Kwan, I., Phillips, H., Kim, D. Y., Yang, I. 2021; 13 (8): e17056

  Abstract

  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.

  View details for DOI 10.7759/cureus.17056

  View details for Web of Science ID 000684202600002

  View details for PubMedID 34522534

  View details for PubMedCentralID PMC8428323

• Comparison of the Safety of Prophylactic Anticoagulants After Intracranial Surgery NEUROSURGERY Bell, J. S., Florence, T. J., Phillips, H., Patel, K., Macaluso, N. J., Villanueva, P. G., Naik, P. K., Kim, W. 2021; 89 (3): 527-536

  Abstract

  Venous thromboembolism (VTE) represents a rare but preventable postoperative complication. Unfractionated heparin (UH) and low-molecular-weight heparin (LMWH) are used to prevent VTE, but comparative studies of their safety and efficacy in the neurosurgical context are limited.To determine the relative safety and efficacy of UH and LMWH for prophylaxis after cranial surgery.We performed a retrospective analysis of 3204 elective intracranial surgical admissions in 2901 patients over the period 2013 to 2018. From chart review, we extracted demographic and clinical features, including diagnosis and procedure, drugs administered, and the occurrence of VTE events. To compare postoperative outcomes, we performed propensity score matching of patients receiving different drugs, and reviewed postoperative cranial imaging. To contextualize our results, we selected 14 prior neurosurgical studies of VTE prophylaxis to compare our outcomes to the existing literature.In our sample of 3204 admissions, the overall rate of VTE was 0.8% (n = 27). Rates of VTE were not statistically different in matched cohorts receiving UH and LMWH (1.7% vs 1.0%, respectively); however, LMWH was associated with a higher rate of clinically significant intracranial hemorrhage (ICH) (3.4% vs 0.5%, P = .008). Literature review and meta-analysis supported these findings. Across studies, UH and LMWH were associated with similar rates of VTE. Studies in which patients received LMWH reported significantly higher rates of ICH (4.9% higher, P = .005).We find that LMWH and UH show similar efficacy in preventing VTE; however, LMWH is associated with higher rates of ICH.

  View details for DOI 10.1093/neuros/nyab221

  View details for Web of Science ID 000692598400057

  View details for PubMedID 34161594

• Pediatric Epilepsy Surgery in Focal and Generalized Epilepsy: Current Trends and Recent Advancements JOURNAL OF PEDIATRIC EPILEPSY Harris, W. B., Phillips, H., Fallah, A., Mathern, G. W. 2021; 10 (02): 88-96

  View details for DOI 10.1055/s-0040-1722298

  View details for Web of Science ID 000609097000002

• Novel tonometer device distinguishes brain stiffness in epilepsy surgery SCIENTIFIC REPORTS Fallah, A., Subramaniam, T., Phillips, H., Michalet, X., Vinters, H. V., Yong, W. H., Wu, J. Y., Salamon, N., Ellingson, B. M., Wang, A. C., Reyes, S. D., Ibrahim, G. M., Weil, A. G., Chang, J. W., Babayan, D., Nguyen, J. C., Behnke, E., Tseng, C., Mathern, G. W. 2020; 10 (1): 20978

  Abstract

  Complete surgical resection of abnormal brain tissue is the most important predictor of seizure freedom following surgery for cortical dysplasia. While lesional tissue is often visually indiscernible from normal brain, anecdotally, it is subjectively stiffer. We report the first experience of the use of a digital tonometer to understand the biomechanical properties of epilepsy tissue and to guide the conduct of epilepsy surgery. Consecutive epilepsy surgery patients (n = 24) from UCLA Mattel Children's Hospital were recruited to undergo intraoperative brain tonometry at the time of open craniotomy for epilepsy surgery. Brain stiffness measurements were corrected with abnormalities on neuroimaging and histopathology using mixed-effects multivariable linear regression. We collected 249 measurements across 30 operations involving 24 patients through the pediatric epilepsy surgery program at UCLA Mattel Children's Hospital. On multivariable mixed-effects regression, brain stiffness was significantly associated with the presence of MRI lesion (β = 32.3, 95%CI 16.3-48.2; p < 0.001), severity of cortical disorganization (β = 19.8, 95%CI 9.4-30.2; p = 0.001), and recent subdural grid implantation (β = 42.8, 95%CI 11.8-73.8; p = 0.009). Brain tonometry offers the potential of real-time intraoperative feedback to identify abnormal brain tissue with millimeter spatial resolution. We present the first experience with this novel intraoperative tool for the conduct of epilepsy surgery. A carefully designed prospective study is required to elucidate whether the clinical application of brain tonometry during resective procedures could guide the area of resection and improve seizure outcomes.

  View details for DOI 10.1038/s41598-020-77888-0

  View details for Web of Science ID 000608976100025

  View details for PubMedID 33262385

  View details for PubMedCentralID PMC7708453

• A systematic analysis of stereotactic radiosurgery surveys for residents in neurosurgery training programs JOURNAL OF THE NEUROLOGICAL SCIENCES Ding, K., Romiyo, P., Ng, E., Udawatta, M., Dejam, D., Phillips, H., Sun, M. Z., Yang, I. 2020; 417: 116867

  Abstract

  The use of stereotactic radiosurgery (SRS) has increased. SRS training has not risen congruently. Neurosurgeons have conducted surveys and advocated implementation of widespread, standardized radiosurgery training. Here we analyze the SRS surveys conducted throughout the past decade.This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic literature review. A broad search of the literature was conducted in October 2018 through the PubMed, Scopus, Embase, and Web of Science databases. This study included surveys evaluating SRS training in neurosurgery and excluded those regarding other specialties.An overview of surveys showed that neurosurgery residents possess gaps in SRS knowledge and procedural competency that have persisted through the past decade. There is an overwhelming sentiment that current radiosurgery training is not adequate to prepare residents for future practice. Our recommendation is for residency programs to integrate formal SRS training electives, with a movement towards creating more options for extended SRS fellowships post-residency.We present data from SRS competency and current training surveys. Although resident SRS training still lags behind other subspecialties, we see indications for growth. To keep up with the role of SRS in neurosurgery, residencies need more formalized SRS rotations.

  View details for DOI 10.1016/j.jns.2020.116867

  View details for Web of Science ID 000570274600014

  View details for PubMedID 32423574

• Epilepsy surgery for Rasmussen encephalitis: the UCLA experience JOURNAL OF NEUROSURGERY-PEDIATRICS Bellamkonda, N., Phillips, H., Chen, J., Tucker, A. M., Maniquis, C., Mathern, G. W., Fallah, A. 2020; 26 (4): 389-397

  Abstract

  Rasmussen encephalitis (RE) is a rare inflammatory neurological disorder typically involving one hemisphere and resulting in drug-resistant epilepsy and progressive neurological decline. Here, the authors present seizure outcomes in children who underwent epilepsy surgery for RE at a single institution.The records of consecutive patients who had undergone epilepsy surgery for RE at the UCLA Mattel Children's Hospital between 1982 and 2018 were retrospectively reviewed. Basic demographic information, seizure history, procedural notes, and postoperative seizure and functional outcome data were analyzed.The cohort included 44 patients, 41 of whom had sufficient data for analysis. Seizure freedom was achieved in 68%, 48%, and 22% of the patients at 1, 5, and 10 years, respectively. The median time to the first seizure for those who experienced seizure recurrence after surgery was 39 weeks (IQR 11-355 weeks). Anatomical hemispherectomy, as compared to functional hemispherectomy, was independently associated with a longer time to postoperative seizure recurrence (HR 0.078, p = 0.03). There was no statistically significant difference in postoperative seizure recurrence between patients with complete hemispherectomy and those who had less-than-hemispheric surgery. Following surgery, 68% of the patients could ambulate and 84% could speak regardless of operative intervention.A large proportion of RE patients will have seizure relapse after surgery, though patients with anatomical hemispherectomies may have a longer time to postoperative seizure recurrence. Overall, the long-term data in this study suggest that hemispheric surgery can be seen as palliative treatment for seizures rather than a cure for RE.

  View details for DOI 10.3171/2020.4.PEDS2098

  View details for Web of Science ID 000583054200007

  View details for PubMedID 32679562

• Seizure outcomes in children with Rasmussen's encephalitis undergoing resective or hemispheric epilepsy surgery: an individual participant data meta-analysis JOURNAL OF NEUROSURGERY-PEDIATRICS Harris, W. B., Phillips, H., Chen, J., Weil, A. G., Ibrahim, G. M., Fallah, A. 2020; 25 (3): 274-283

  Abstract

  The objective of this study was to perform an individual participant data meta-analysis to identify preoperative factors associated with a good seizure outcome in children with Rasmussen's encephalitis (RE) undergoing resective or hemispheric epilepsy surgery.Electronic databases (PubMed, Web of Science, CINAHL) were searched with no language or date restrictions to identify cohort studies of consecutive participants undergoing resective surgery that reported seizure outcomes. The authors recorded all preoperative factors that could plausibly be associated with seizure outcomes and used Cox regression analysis to identify which of these variables were associated with seizure freedom (i.e., Engel class I).Of 720 citations, 19 articles reporting on 187 participants were eligible. Seizure freedom (Engel class I) was observed in 113 participants (60.4%). On univariate analyses, younger age at disease onset (hazard ratio [HR] 0.906, p = 0.001), younger age at surgery (HR 0.928, p < 0.001), shorter time to surgery (HR 0.921, p = 0.001), and hemispherectomy (HR 0.283, p < 0.001) were all associated with longer time to postoperative seizure recurrence. Additionally, multivariable analysis including the aforementioned variables showed that younger age at surgery (HR 0.946, p = 0.043) and hemispherectomy (HR 0.297, p < 0.001) were independently and significantly associated with a greater time to seizure recurrence and longer duration of seizure freedom.The majority of pediatric patients undergoing resective or hemispheric surgery for RE achieve good seizure outcome. Although small retrospective cohort studies are inherently prone to bias, the best available evidence utilizing individual participant data suggests hemispheric surgery and younger age at surgery are associated with good seizure outcomes following epilepsy surgery. Large, multicenter observational studies with long-term follow-up are required to evaluate the risk factors identified in this review.

  View details for DOI 10.3171/2019.9.PEDS19380

  View details for Web of Science ID 000518390100010

  View details for PubMedID 31812145

• Social Media Use for Professional Purposes in the Neurosurgical Community: A Multi-Institutional Study WORLD NEUROSURGERY Phillips, H., Chen, J., Wilson, B., Udawatta, M., Prashant, G., Nagasawa, D., Yang, I. 2019; 129: E367-E374

  Abstract

  Since the debut of Facebook in 2004, social media (SoMe) has garnered increased popularity and usage worldwide. Given its appeal and visibility, many industries have used SoMe to promote products for professional purposes. Specialized sites have subsequently been created to connect users in similar disciplines. Although SoMe sites have amassed over 1-billion followers, SoMe usage in the neurosurgical community has not yet been well described.We present an online survey administered to neurosurgery faculty, fellows, and residents in 102 U.S. accredited programs to gauge usage and perception of SoMe for professional purposes.Of all surveys distributed, 241 neurosurgeons responded with an attending, resident, to fellow breakdown of 137, 96, and 8, respectively. A total of 55.97% of respondents were under the age of 34, 2% were over the age of 75, and 81% of respondents identified as men. An overwhelming majority cited conferences (83%) and in-person meetings as their preferred method of networking. However, 70% state they use SoMe for professional purposes with Doximity and LinkdIn listed as the most popular (49% and 48%, respectively) platforms. Lack of time and perceived value, in addition to privacy concerns, were noted to be the main factors for those refraining from SoMe use.As SoMe becomes increasingly popular and its use expands, the majority of neurosurgeon respondents are also using SoMe for professional purposes. Although lack of time, lack of perceived value, and privacy concerns were hindrances to usage, other factors like age do not seem to correlate with SoMe adoption for professional aims.

  View details for DOI 10.1016/j.wneu.2019.05.154

  View details for Web of Science ID 000481607900046

  View details for PubMedID 31132504

• Radiosurgery treatment is associated with improved facial nerve preservation versus repeat resection in recurrent vestibular schwannomas ACTA NEUROCHIRURGICA Romiyo, P., Ng, E., Dejam, D., Ding, K., Sheppard, J. P., Duong, C., Franks, A., Ong, V., Udawatta, M., Phillips, H., Gopen, Q., Yang, I. 2019; 161 (7): 1449-1456

  Abstract

  Vestibular schwannomas (VSs) are benign neoplasms of the Schwann cells of cranial nerve VIII, and treatment of VS typically involves surgical resection. However, tumor recurrence may necessitate reintervention, and secondary treatment modalities include repeat surgical resection or adjuvant radiosurgery. The purpose of this study is to examine the scientific literature in order to determine whether surgical resection or radiosurgery for recurrent VS results in better tumor control, hearing preservation, and preservation of facial nerve function.The PubMed, Scopus, Embase, Cochrane, and Web of Science databases were searched for studies reporting on patients undergoing either radiosurgery or repeat surgical resection after primary surgical resection for recurrent VS. Statistical analyses were performed on the compiled data, primarily outcome data involving tumor control, hearing preservation, and preservation of facial nerve function.We analyzed the data of 15 individual studies involving 359 total patients, and our results reveal that tumor control rates are comparable between adjuvant radiosurgery (91%, CI: 88-94%) and secondary resection (92%, CI 75-98%). However, adjuvant radiosurgery was shown to preserve good facial nerve function better (94%, CI 84-98%) compared to secondary surgical resection (56%, CI 41-69%).With comparable tumor control rates and better preservation of good facial nerve function, this study suggests that secondary radiosurgery for recurrent VS is associated with both optimal tumor control and preservation of good facial nerve function.

  View details for DOI 10.1007/s00701-019-03940-2

  View details for Web of Science ID 000472004700028

  View details for PubMedID 31129783

• Age-related differences in social media use in the neurosurgical community: A multi-institutional study CLINICAL NEUROLOGY AND NEUROSURGERY Udawatta, M., Ng, E., Phillips, H., Chen, J., Wilson, B., Prashant, G. N., Nagasawa, D. T., Yang, I. 2019; 180: 97-100

  Abstract

  Social media is evolving and growing at an exponential rate today. From a healthcare perspective, these platforms can be used to enhance professional networking, education, organizational promotion, patient care, patient education, and public health programs without the limitations of geographic and time-related access barriers. Given the possible importance of social media in medicine, and the conflicting reports in literature about its use in healthcare, it is important to identify its utility within the neurosurgical community. We set out to measure the use of social media platforms among neurosurgery faculty, fellows, and residents.An online survey using the SurveyMonkey platform was sent to the program directors of 102 accredited neurosurgery programs across the United States. Program directors then distributed these surveys to the residents, fellows, and attendings at their respective institutions once each month between October 2017 and December 2017. Neurosurgeons participated anonymously, voluntarily, and received no compensation for their participation. Statistical analysis was performed using the IBM SPSS Statistics for Windows, Version 25 (IBM SPSS Statistics for Windows, IBM Corporation, Armonk, NY).137 attendings, 96 residents, and 8 fellows responded to the survey (81% male). Most (70%) stated that they used social media for professional purposes. Sixty percent of all respondents believed that social media can be beneficial in terms of professional development. Younger neurosurgeons in training were more likely to read journal articles found via social media and were more likely to believe social media could be beneficial than older neurosurgeons at later stages in their career.Results point toward differences in social media use based on age or level of training. Further studies should include a larger sample cohort over a longer time period to determine whether these trends will change over time.

  View details for DOI 10.1016/j.clineuro.2019.03.027

  View details for Web of Science ID 000466822800017

  View details for PubMedID 30953974

  View details for PubMedCentralID PMC6488041

• Acute postoperative sialadenitis after retrosigmoid craniotomies JOURNAL OF NEUROSURGICAL SCIENCES Phillips, H. W., Abdullah, K. G., Learned, K. O., Nayak, N., McLaughlin, E., Lee, J. K. 2016; 60 (3): 403-404

  View details for Web of Science ID 000384947400018

  View details for PubMedID 27402408

• Time interval to surgery and outcomes following the surgical treatment of acute traumatic subdural hematoma JOURNAL OF CLINICAL NEUROSCIENCE Walcott, B. P., Khanna, A., Kwon, C., Phillips, H., Nahed, B. V., Coumans, J. 2014; 21 (12): 2107-2111

  Abstract

  Although the pre-surgical management of patients with acute traumatic subdural hematoma prioritizes rapid transport to the operating room, there is conflicting evidence regarding the importance of time interval from injury to surgery with regards to outcomes. We sought to determine the association of surgical timing with outcomes for subdural hematoma. A retrospective review was performed of 522 consecutive patients admitted to a single center from 2006-2012 who underwent emergent craniectomy for acute subdural hematoma. After excluding patients with unknown time of injury, penetrating trauma, concurrent cerebrovascular injury, epidural hematoma, or intraparenchymal hemorrhage greater than 30 mL, there remained 45 patients identified for analysis. Using a multiple regression model, we examined the effect of surgical timing, in addition to other variables on in-hospital mortality (primary outcome), as well as the need for tracheostomy or gastrostomy (secondary outcome). We found that increasing injury severity score (odds ratio [OR] 1.146; 95% confidence interval [CI] 1.035-1.270; p=0.009) and age (OR1.066; 95%CI 1.006-1.129; p=0.031) were associated with in-hospital mortality in multivariate analysis. In this model, increasing time to surgery was not associated with mortality, and in fact had a significant effect in decreasing mortality (OR 0.984; 95%CI 0.971-0.997; p=0.018). Premorbid aspirin use was associated with a paradoxical decrease in mortality (OR 0.019; 95%CI 0.001-0.392; p=0.010). In this patient sample, shorter time interval from injury to surgery was not associated with better outcomes. While there are potential confounding factors, these findings support the evaluation of rigorous preoperative resuscitation as a priority in future study.

  View details for DOI 10.1016/j.jocn.2014.05.016

  View details for Web of Science ID 000346622900010

  View details for PubMedID 25065950

  View details for PubMedCentralID PMC4250331

• Utility of foramen ovale electrodes in mesial temporal lobe epilepsy EPILEPSIA Sheth, S. A., Aronson, J. P., Shafi, M. M., Phillips, H., Velez-Ruiz, N., Walcott, B. P., Kwon, C., Mian, M. K., Dykstra, A. R., Cole, A., Eskandar, E. N. 2014; 55 (5): 713-724

  Abstract

  To determine the ability of foramen ovale electrodes (FOEs) to localize epileptogenic foci after inconclusive noninvasive investigations in patients with suspected mesial temporal lobe epilepsy (MTLE).We identified patients with medically intractable epilepsy who had undergone FOE investigation for initial invasive monitoring at our institution between 2005 and 2012. Indications for initiating FOE investigation were grouped into four categories: (1) bilateral anterior temporal ictal activity on scalp electroencephalography (EEG), (2) unclear laterality of scalp EEG onset due to muscle artifact or significant delay following clinical manifestation, (3) discordance between ictal and interictal discharges, and (4) investigation of a specific anatomic abnormality or competing putative focus. The FOE investigation was classified as informative if it provided sufficient evidence to make a treatment decision.Forty-two consecutive patients underwent FOE investigation, which was informative in 38 patients (90.5%). Of these 38 patients, 24 were determined to be appropriate candidates for resective surgery. Five were localized sufficiently for surgery, but were considered high risk for verbal memory deficit, and nine were deemed poor surgical candidates because of bilateral ictal origins. The remaining 4 of 42 patients had inconclusive FOE studies and were referred for further invasive investigation. Of the 18 patients who underwent resective surgery, 13 (72%) were seizure-free (Engel class I) at last follow-up (mean 22.5 months).More than 90% of our 42 FOE studies provided sufficient evidence to render treatment decisions. When undertaken with an appropriate hypothesis, FOE investigations are a minimally invasive and efficacious means for evaluating patients with suspected MTLE after an inconclusive noninvasive investigation.

  View details for DOI 10.1111/epi.12571

  View details for Web of Science ID 000336623200018

  View details for PubMedID 24605889

• Neurosurgical management for complicated catastrophic antiphospholipid syndrome JOURNAL OF CLINICAL NEUROSCIENCE Drazin, D., Phillips, H., Shirzadi, A., Drazin, N., Schievink, W. 2014; 21 (4): 680-683

  Abstract

  Antiphospholipid syndrome (APS) is an autoimmune condition involving arterial and venous thrombosis. An unusual APS variant, catastrophic antiphospholipid syndrome (CAPS), includes rapid multi-organ failure from widespread small vessel thrombosis. Central nervous system complications arise in one-third of CAPS patients. In rare cases, CAPS co-manifests with cerebellar hemorrhage presenting a neurosurgical emergency. We present a 65-year-old woman with CAPS-related cerebellar hematoma, co-morbid idiopathic thrombocytopenic purpura, deep vein thrombosis and altered mental status, with treatment complicated by thrombocytopenia. The patient suddenly deteriorated, secondary to a cerebellar subdural hematoma, and underwent decompression and excision of the hematoma. After recovery in the intensive care unit, she developed a new spontaneous epidural hematoma requiring additional surgery. Management of these patients is hematologically complex and often requires a multi-disciplinary team of physicians. This patient provides an important learning point for clinicians - consider CAPS when hemorrhage and thrombosis are present.

  View details for DOI 10.1016/j.jocn.2013.05.016

  View details for Web of Science ID 000333723600029

  View details for PubMedID 24269552

• Sports-related concussion: Anonymous survey of a collegiate cohort. Neurology. Clinical practice Torres, D. M., Galetta, K. M., Phillips, H. W., Dziemianowicz, E. M., Wilson, J. A., Dorman, E. S., Laudano, E., Galetta, S. L., Balcer, L. J. 2013; 3 (4): 279-287

  Abstract

  Studies suggest that a lack of standardized knowledge may lead to underreporting and undertreatment of sports-related concussion. However, there has been little work done to establish how this knowledge may affect athletes' behaviors toward reporting their concussions and removing themselves from play. We conducted an anonymous online survey to assess athletes' knowledge of signs and symptoms of concussion, and also sought to estimate the potential frequency of underreporting in a collegiate athlete cohort. Among 262 athletes who responded to the survey, 43% of those with a history of concussion reported that they had knowingly hidden symptoms of a concussion to stay in a game, and 22% of athletes overall indicated that they would be unlikely or very unlikely to report concussion symptoms to a coach or athletic trainer in the future. These data suggest that there may be a substantial degree of underreporting of concussion among collegiate athletes, despite most acknowledging that they have been formally educated about the risks of concussion.

  View details for PubMedID 24195017

• Nanobiopolymer for Direct Targeting and Inhibition of EGFR Expression in Triple Negative Breast Cancer PLOS ONE Inoue, S., Patil, R., Portilla-Arias, J., Ding, H., Konda, B., Espinoza, A., Mongayt, D., Markman, J. L., Elramsisy, A., Phillips, H., Black, K. L., Holler, E., Ljubimova, J. Y. 2012; 7 (2): e31070

  Abstract

  Treatment options for triple negative breast cancer (TNBC) are generally limited to cytotoxic chemotherapy. Recently, anti-epidermal growth factor receptor (EGFR) therapy has been introduced for TNBC patients. We engineered a novel nanobioconjugate based on a poly(β-L-malic acid) (PMLA) nanoplatform for TNBC treatment. The nanobioconjugate carries anti-tumor nucleosome-specific monoclonal antibody (mAb) 2C5 to target breast cancer cells, anti-mouse transferrin receptor (TfR) antibody for drug delivery through the host endothelial system, and Morpholino antisense oligonucleotide (AON) to inhibit EGFR synthesis. The nanobioconjugates variants were: (1) P (BioPolymer) with AON, 2C5 and anti-TfR for tumor endothelial and cancer cell targeting, and EGFR suppression (P/AON/2C5/TfR), and (2) P with AON and 2C5 (P/AON/2C5). Controls included (3) P with 2C5 but without AON (P/2C5), (4) PBS, and (5) P with PEG and leucine ester (LOEt) for endosomal escape (P/mPEG/LOEt). Drugs were injected intravenously to MDA-MB-468 TNBC bearing mice. Tissue accumulation of injected nanobioconjugates labeled with Alexa Fluor 680 was examined by Xenogen IVIS 200 (live imaging) and confocal microscopy of tissue sections. Levels of EGFR, phosphorylated and total Akt in tumor samples were detected by western blotting. In vitro western blot showed that the leading nanobioconjugate P/AON/2C5/TfR inhibited EGFR synthesis significantly better than naked AON. In vivo imaging revealed that 2C5 increased drug-tumor accumulation. Significant tumor growth inhibition was observed in mice treated with the lead nanobioconjugate (1) [P = 0.03 vs. controls; P<0.05 vs. nanobioconjugate variant (2)]. Lead nanobioconjugate (1) also showed stronger inhibition of EGFR expression and Akt phosphorylation than other treatments. Treatment of TNBC with the new nanobioconjugate results in tumor growth arrest by inhibiting EGFR and its downstream signaling intermediate, phosphorylated Akt. The nanobioconjugate represents a new generation of nanodrugs for treatment of TNBC.

  View details for DOI 10.1371/journal.pone.0031070

  View details for Web of Science ID 000302741300036

  View details for PubMedID 22355336

  View details for PubMedCentralID PMC3280290

• Noradrenergic Control of Cortico-Striato-Thalamic and Mesolimbic Cross-Structural Synchrony JOURNAL OF NEUROSCIENCE Dzirasa, K., Phillips, H., Sotnikova, T. D., Salahpour, A., Kumar, S., Gainetdinov, R. R., Caron, M. G., Nicolelis, M. L. 2010; 30 (18): 6387-6397

  Abstract

  Although normal dopaminergic tone has been shown to be essential for the induction of cortico-striatal and mesolimbic theta oscillatory activity, the influence of norepinephrine on these brain networks remains relatively unknown. To address this question, we simultaneously recorded local field potentials and single-neuron activity across 10 interconnected brain areas (ventral striatum, frontal association cortex, hippocampus, primary motor cortex, orbital frontal cortex, prelimbic cortex, dorsal lateral striatum, medial dorsal nucleus of thalamus, substantia nigra pars reticularis, and ventral tegmental area) in a combined genetically and pharmacologically induced mouse model of hyponoradrenergia. Our results show that norepinephrine (NE) depletion induces a novel state in male mice characterized by a profound disruption of coherence across multiple cortico-striatal circuits and an increase in mesolimbic cross-structural coherence. Moreover, this brain state is accompanied by a complex behavioral phenotype consisting of transient hyperactivity, stereotypic behaviors, and an acute 12-fold increase in grooming. Notably, treatment with a norepinephrine precursors (l-3,4-dihydroxyphenylalanine at 100 mg/kg or l-threo-dihydroxyphenylserine at 5 mg/kg) or a selective serotonin reuptake inhibitor (fluoxetine at 20 mg/kg) attenuates the abnormal behaviors and selectively reverses the circuit changes observed in NE-depleted mice. Together, our results demonstrate that norepinephrine modulates the dynamic tuning of coherence across cortico-striato-thalamic circuits, and they suggest that changes in coherence across these circuits mediate the abnormal generation of hyperactivity and repetitive behaviors.

  View details for DOI 10.1523/JNEUROSCI.0764-10.2010

  View details for Web of Science ID 000277358300025

  View details for PubMedID 20445065

  View details for PubMedCentralID PMC2988440