Publications by authors named "Aria Fallah"

101 Publications

Epilepsy surgery in infants up to 3 months of age: Safety, feasibility, and outcomes: A multicenter, multinational study.

Epilepsia 2021 Jun 14. Epub 2021 Jun 14.

Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

Objective: Drug-resistant epilepsy (DRE) during the first few months of life is challenging and necessitates aggressive treatment, including surgery. Because the most common causes of DRE in infancy are related to extensive developmental anomalies, surgery often entails extensive tissue resections or disconnection. The literature on "ultra-early" epilepsy surgery is sparse, with limited data concerning efficacy controlling the seizures, and safety. The current study's goal is to review the safety and efficacy of ultra-early epilepsy surgery performed before the age of 3 months.

Methods: To achieve a large sample size and external validity, a multinational, multicenter retrospective study was performed, focusing on epilepsy surgery for infants younger than 3 months of age. Collected data included epilepsy characteristics, surgical details, epilepsy outcome, and complications.

Results: Sixty-four patients underwent 69 surgeries before the age of 3 months. The most common pathologies were cortical dysplasia (28), hemimegalencephaly (17), and tubers (5). The most common procedures were hemispheric surgeries (48 procedures). Two cases were intentionally staged, and one was unexpectedly aborted. Nearly all patients received blood products. There were no perioperative deaths and no major unexpected permanent morbidities. Twenty-five percent of patients undergoing hemispheric surgeries developed hydrocephalus. Excellent epilepsy outcome (International League Against Epilepsy [ILAE] grade I) was achieved in 66% of cases over a median follow-up of 41 months (19-104 interquartile range [IQR]). The number of antiseizure medications was significantly reduced (median 2 drugs, 1-3 IQR, p < .0001). Outcome was not significantly associated with the type of surgery (hemispheric or more limited resections).

Significance: Epilepsy surgery during the first few months of life is associated with excellent seizure control, and when performed by highly experienced teams, is not associated with more permanent morbidity than surgery in older infants. Thus surgical treatment should not be postponed to treat DRE in very young infants based on their age.
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http://dx.doi.org/10.1111/epi.16959DOI Listing
June 2021

Functional hemispherectomy: can preoperative imaging predict outcome?

J Neurosurg Pediatr 2020 Jun 21;25(6). Epub 2020 Feb 21.

Division of Pediatric Neurosurgery, Department of Neurosurgery, Brain Institute, Miami Children's Hospital, Miami, Florida.

Objective: Although hemispherectomy is an effective treatment for children with intractable hemispheric epilepsy syndromes, as many as 40% of patients eventually develop seizure recurrence. The causes of seizure recurrence in these patients are incompletely understood. The authors sought to evaluate the efficacy of hemispherectomy at their center and determine whether contralateral MRI abnormalities can predict seizure recurrence.

Methods: A retrospective review of consecutive hemispherectomies performed at Miami Children's Hospital between January 2000 and June 2014 was performed. Time-to-event analysis was performed. The "event" was defined as any seizures following resective epilepsy surgery (not including seizures in the first postoperative week and auras). Several preoperative variables were analyzed to determine their suitability to predict seizure recurrence following surgery.

Results: Sixty-nine patients (44 boys) with a mean age of 8.2 ± 5.9 years (range 0.1-20.8 years) underwent 72 hemispherectomies; 67 of these were functional hemispherectomies, while another 5 were completion of a previous functional hemispherectomy (2 completions of functional hemispherectomies, 3 anatomical hemispherectomies). The duration of epilepsy was 5.8 ± 5.5 years with 66 cases (91.7%) having daily seizures. Etiology included stroke (n = 28), malformation of cortical development (n = 11), hemimegalencephaly (n = 11), encephalitis (n = 13), and other (n = 7). Engel class I outcome was achieved in 59 (86%) and 56 (81%) patients at 1 and 2 years of follow-up, respectively. The mean time to seizure recurrence was 33.5 ± 31.1 months. In univariate analyses, the absence of contralateral abnormalities on MRI (HR 4.09, 95% CI 1.41-11.89, p = 0.009) was associated with a longer duration of seizure freedom. The presence of contralateral MRI abnormalities was associated with contralateral ictal seizures on preoperative scalp EEG (p = 0.002). Fifteen patients experienced 20 complications (20/72, 27.8%), including the development of hydrocephalus necessitating CSF diversion in 9 cases (13%), hygroma in 1, hemispheric edema in 1, aseptic meningitis in 2, postoperative hemorrhage in 2, infection in 2, ischemic stroke in 2, and blood transfusion-contracted hepatitis C in 1 case.

Conclusions: Patients with bihemispheric abnormalities, as evidenced by contralateral MRI abnormalities, have a higher risk of earlier seizure recurrence following functional hemispherectomy.

Abbreviations: EVD = external ventricular drain; MCD = malformation of cortical development; MEG = magnetoencephalography; PVWM = periventricular white matter; TTE = time-to-event; VPS = ventriculoperitoneal shunt.
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http://dx.doi.org/10.3171/2019.12.PEDS19370DOI Listing
June 2020

Systematic review on use and efficacy of selective dorsal rhizotomy (SDR) for the management of spasticity in non-pediatric patients.

Childs Nerv Syst 2021 Jun 29;37(6):1837-1847. Epub 2021 Apr 29.

Division of Pediatric Neurosurgery, Children's Hospital of Eastern Ontario, Rm 3359 CHEO, 401 Smyth Rd, Ottawa, ON, K1H 8L1, Canada.

Purpose: Selective dorsal rhizotomy (SDR) has been used to improve mobility and reduce lower extremity spasticity in patients with a various CNS conditions. Incidentally, literature on SDR has been performed in the pediatric population as such there is a paucity of research on the use in adult patients.

Methods: Studies describing SDR in adults were identified from Medline and Embase databases. Combinations of search terms "Selective Dorsal Rhizotomy," "Selective Posterior Rhizotomy," and "Adult" were used. Only literature in English language on patients over the age of 18 years and that included measures for lower extremity outcome (i.e., spasticity, mobility) were included. Case reports, reviews without primary data, or inaccessible publications were excluded.

Results: One hundred twenty-nine publications between 1970 and 2019 were identified. Twelve of these publications fit the inclusion criteria (n = 141 patients). In series where it was reported, SDR resulted in ambulatory improvement (54%, n = 44 out of 81), reduced spasticity (75.2%, n = 106 out of 141), and minimized muscle and joint pain (74.5%, n = 64 out of 86). SDR also showed improvement in parameters of the activities of daily life. 92.3% (n = 48 out of 52) of patients post-SDR developed new lower limb paresthesia.

Conclusion: The success and efficacy appear durable in the short-term, but further follow-up is necessary to validate these findings. The goal of the intervention dictates the ideal adult patient for SDR. Patients seeking ambulatory improvement, any etiology of spasticity besides MS, seem favorable. Positive locomotive predictors include the ability to isolate lower extremity function, lack of contractures, lower limb strength, and post-SDR physiotherapy.
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http://dx.doi.org/10.1007/s00381-021-05167-yDOI Listing
June 2021

Understanding the sodium cation conductivity of human epileptic brain tissue.

AIP Adv 2021 Apr 16;11(4):045118. Epub 2021 Apr 16.

Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA.

Transient and frequency-dependent conductivity measurements on excised brain-tissue lesions from epilepsy patients indicate that sodium cations are the predominant charge carriers. The transient conductivity ultimately vanishes as ions encounter blockages. The initial and final values of the transient conductivity correspond to the high-frequency and low-frequency limits of the frequency-dependent conductivity, respectively. Carrier dynamics determines the conductivity between these limits. Typically, the conductivity rises monotonically with increasing frequency. By contrast, when pathology examinations found exceptionally disorganized excised tissue, the conductivity falls with increasing frequency as it approaches its high-frequency limit. To analyze these measurements, excised tissues are modeled as mixtures of "normal" tissue within which sodium cations can diffuse and "abnormal" tissue within which sodium cations are trapped. The decrease in the conductivity with increasing frequency indicates the predominance of trapping. The high-frequency conductivity decreases as the rate with which carriers are liberated from traps decreases. A relatively low conductivity results when most sodium cations remain trapped in "abnormal" brain tissue, while few move within "normal" brain tissue. Thus, the high densities of sodium nuclei observed by Na-MRI in epilepsy patients' lesions are consistent with the low densities of diffusing sodium cations inferred from conductivity measurements of excised lesions.
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http://dx.doi.org/10.1063/5.0041906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053039PMC
April 2021

Clonally Focused Public and Private T Cells in Resected Brain Tissue From Surgeries to Treat Children With Intractable Seizures.

Front Immunol 2021 6;12:664344. Epub 2021 Apr 6.

Department of Neurosurgery, David Geffen School of Medicine at the University of California, Los Angeles, CA, United States.

Using a targeted transcriptomics approach, we have analyzed resected brain tissue from a cohort of 53 pediatric epilepsy surgery cases, and have found that there is a spectrum of involvement of both the innate and adaptive immune systems as evidenced by the differential expression of immune-specific genes in the affected brain tissue. The specimens with the highest expression of immune-specific genes were from two Rasmussen encephalitis cases, which is known to be a neuro-immunological disease, but also from tuberous sclerosis complex (TSC), focal cortical dysplasia, and hemimegalencephaly surgery cases. We obtained T cell receptor (TCR) Vβ chain sequence data from brain tissue and blood from patients with the highest levels of T cell transcripts. The clonality indices and the frequency of the top 50 Vβ clonotypes indicated that T cells in the brain were clonally restricted. The top 50 Vβ clonotypes comprised both public and private (patient specific) clonotypes, and the TCR Vβ chain third complementarity region (CDR3) of the most abundant public Vβ clonotype in each brain sample was strikingly similar to a CDR3 that recognizes an immunodominant epitope in either human cytomegalovirus or Epstein Barr virus, or influenza virus A. We found that the frequency of 14 of the top 50 brain Vβ clonotypes from a TSC surgery case had significantly increased in brain tissue removed to control recurrent seizures 11 months after the first surgery. Conversely, we found that the frequency in the blood of 18 of the top 50 brain clonotypes from a second TSC patient, who was seizure free, had significantly decreased 5 months after surgery indicating that T cell clones found in the brain had contracted in the periphery after removal of the brain area associated with seizure activity and inflammation. However, the frequency of a public and a private clonotype significantly increased in the brain after seizures recurred and the patient underwent a second surgery. Combined single cell gene expression and TCR sequencing of brain-infiltrating leukocytes from the second surgery showed that the two clones were CD8 effector T cells, indicating that they are likely to be pathologically relevant.
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http://dx.doi.org/10.3389/fimmu.2021.664344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056262PMC
April 2021

Hemispherectomy Outcome Prediction Scale: Development and validation of a seizure freedom prediction tool.

Epilepsia 2021 May 13;62(5):1064-1073. Epub 2021 Mar 13.

Department of Pediatrics, BC Children's Hospital and University of British Columbia, Vancouver, British Columbia, Canada.

Objective: To develop and validate a model to predict seizure freedom in children undergoing cerebral hemispheric surgery for the treatment of drug-resistant epilepsy.

Methods: We analyzed 1267 hemispheric surgeries performed in pediatric participants across 32 centers and 12 countries to identify predictors of seizure freedom at 3 months after surgery. A multivariate logistic regression model was developed based on 70% of the dataset (training set) and validated on 30% of the dataset (validation set). Missing data were handled using multiple imputation techniques.

Results: Overall, 817 of 1237 (66%) hemispheric surgeries led to seizure freedom (median follow-up = 24 months), and 1050 of 1237 (85%) were seizure-free at 12 months after surgery. A simple regression model containing age at seizure onset, presence of generalized seizure semiology, presence of contralateral 18-fluoro-2-deoxyglucose-positron emission tomography hypometabolism, etiologic substrate, and previous nonhemispheric resective surgery is predictive of seizure freedom (area under the curve = .72). A Hemispheric Surgery Outcome Prediction Scale (HOPS) score was devised that can be used to predict seizure freedom.

Significance: Children most likely to benefit from hemispheric surgery can be selected and counseled through the implementation of a scale derived from a multiple regression model. Importantly, children who are unlikely to experience seizure control can be spared from the complications and deficits associated with this surgery. The HOPS score is likely to help physicians in clinical decision-making.
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http://dx.doi.org/10.1111/epi.16861DOI Listing
May 2021

Commentary: Magnetic Resonance-Guided Laser Interstitial Thermal Therapy for Palliative Rhizotomy: A Novel Technical Application.

Oper Neurosurg (Hagerstown) 2021 04;20(5):E388-E389

Division of Neurosurgery, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.

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http://dx.doi.org/10.1093/ons/opab025DOI Listing
April 2021

Novel tonometer device distinguishes brain stiffness in epilepsy surgery.

Sci Rep 2020 12 1;10(1):20978. Epub 2020 Dec 1.

Department of Neurosurgery, David Geffen School of Medicine at UCLA, 300 Stein Plaza, Suite 525, Los Angeles, CA, 90095-6901, USA.

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.
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http://dx.doi.org/10.1038/s41598-020-77888-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708453PMC
December 2020

A needs assessment of pediatric epilepsy surgery in Haiti.

J Neurosurg Pediatr 2020 Nov 27:1-7. Epub 2020 Nov 27.

3Division of Neurosurgery, Department of Surgery, University of Toronto, Ontario.

Objective: Epilepsy disproportionately affects low- and/or middle-income countries (LMICs). Surgical treatments for epilepsy are potentially curative and cost-effective and may improve quality of life and reduce social stigmas. In the current study, the authors estimate the potential need for a surgical epilepsy program in Haiti by applying contemporary epilepsy surgery referral guidelines to a population of children assessed at the Clinique d'Épilepsie de Port-au-Prince (CLIDEP).

Methods: The authors reviewed 812 pediatric patient records from the CLIDEP, the only pediatric epilepsy referral center in Haiti. Clinical covariates and seizure outcomes were extracted from digitized charts. Electroencephalography (EEG) and neuroimaging reports were further analyzed to determine the prevalence of focal epilepsy or surgically amenable syndromes and to assess the lesional causes of epilepsy in Haiti. Lastly, the toolsforepilepsy instrument was applied to determine the proportion of patients who met the criteria for epilepsy surgery referral.

Results: Two-thirds of the patients at CLIDEP (543/812) were determined to have epilepsy based on clinical and diagnostic evaluations. Most of them (82%, 444/543) had been evaluated with interictal EEG, 88% of whom (391/444) had abnormal findings. The most common finding was a unilateral focal abnormality (32%, 125/391). Neuroimaging, a prerequisite for applying the epilepsy surgery referral criteria, had been performed in only 58 patients in the entire CLIDEP cohort, 39 of whom were eventually diagnosed with epilepsy. Two-thirds (26/39) of those patients had abnormal findings on neuroimaging. Most patients (55%, 18/33) assessed with the toolsforepilepsy application met the criteria for epilepsy surgery referral.

Conclusions: The authors' findings suggest that many children with epilepsy in Haiti could benefit from being evaluated at a center with the capacity to perform basic brain imaging and neurosurgical treatments.
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http://dx.doi.org/10.3171/2020.7.PEDS20256DOI Listing
November 2020

The Child & Youth CompreHensIve Longitudinal Database for Deep Brain Stimulation (CHILD-DBS).

Childs Nerv Syst 2021 02 15;37(2):607-615. Epub 2020 Sep 15.

Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada.

Purpose: Deep brain stimulation (DBS) is a common tool for the treatment of movement disorders in adults; however, it remains an emerging treatment modality in children with a growing number of indications, including epilepsy and dystonia. The Child & Youth CompreHensIve Longitudinal Database of DBS (CHILD-DBS) study aims to prospectively collect relevant data on quality of life (QoL), safety, efficacy, and long-term neurodevelopmental outcomes following DBS in children.

Methods: Data are collected and managed using the Research Electronic Data Capture (REDCap). This database aims to collect multicentre comprehensive and longitudinal clinical, QoL, imaging and electrophysiologic data for children under the age of 19 undergoing DBS.

Results: Both general and indication-specific measures are collected at baseline and at four time points postoperatively: 6 months, 1 year, 2 years, and 3 years. The database encompasses QoL metrics for children, including the PedsQL (Pediatric Quality of Life Inventory, generic), QOLCE (Quality of Life in Childhood Epilepsy Questionnaire, parent-rated), CHU 9D (Child Health Utility 9D), and KIDSCREEN. Caregiver clinical and QoL metrics, including QIDS (Quick Inventory of Depressive Symptomatology), GAD-7 (Generalized Anxiety Disorder 7-item scale), and CarerQoL-7D (The Care-related Quality of Life Instrument), are similarly prospectively collected. Healthcare resource utilization is also assessed before and after DBS. Lastly, stimulation parameters and radiographic and electrophysiologic data are collected within the database.

Conclusions: The development of the current prospective paediatric DBS database with carefully selected physical and psychosocial outcomes and assessments will complement existing efforts to enhance and facilitate multisite collaboration to further understand the role of DBS in childhood.
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http://dx.doi.org/10.1007/s00381-020-04880-4DOI Listing
February 2021

Effect of Gene Mutation on Seizures in Surgery for Tuberous Sclerosis Complex.

Can J Neurol Sci 2021 May 28;48(3):327-334. Epub 2020 Aug 28.

Department of Neurosurgery, University of California Los Angeles, Los Angeles, CA, USA.

Background: Tuberous sclerosis complex (TSC) is a rare genetic disorder that commonly leads to drug-resistant epilepsy in affected patients. This study aimed to determine whether the underlying genetic mutation (TSC1 vs. TSC2) predicts seizure outcomes following surgical treatments for epilepsy.

Methods: We retrospectively assessed TSC patients using the TSC Natural History Database core registry. Data review focused on outcomes in patients treated with surgical resection or vagus nerve stimulation.

Results: A total of 42 patients with a TSC1 mutation, and 145 patients with a TSC2 mutation, were identified. We observed a distinct clinical phenotype: children with TSC2 mutations tended to be diagnosed with TSC at a younger age than those with a TSC1 mutation (p < 0.001), were more likely to have infantile spasms (p < 0.001), and to get to surgery at a later age (p = 0.003). Among this TSC2 cohort, seizure control following resective epilepsy surgery was achieved in less than half (47%) the study sample. In contrast, patients with TSC1 mutations tended to have more favorable postsurgical outcomes; seizure control was achieved in 66% of this group.

Conclusion: TSC2 mutations result in a more severe epilepsy phenotype that is also less responsive to resective surgery. It is important to consider this distinct clinical disposition when counseling families preoperatively with respect to seizure freedom. Larger samples are required to better characterize the independent effects of genetic mutation, infantile spasms, and duration of epilepsy as they relate to seizure control following resective or neuromodulatory epilepsy surgery.
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http://dx.doi.org/10.1017/cjn.2020.185DOI Listing
May 2021

Epilepsy surgery for Rasmussen encephalitis: the UCLA experience.

J Neurosurg Pediatr 2020 Jul 17:1-9. Epub 2020 Jul 17.

Departments of1Neurosurgery.

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.3171/2020.4.PEDS2098DOI Listing
July 2020

Assessment and treatment of childhood epilepsy in Haiti.

Epilepsia Open 2020 Jun 2;5(2):190-197. Epub 2020 Mar 2.

Division of Neurosurgery Department of Surgery University of Toronto Toronto ON Canada.

Objective: The global burden of pediatric epilepsy is disproportionately concentrated in low- and middle-income countries (LMICs). However, little is known about the effectiveness of current treatment programs in this setting. We present the outcomes of children who were assessed and treated at the Clinique D'Épilepsie de Port-au-Prince (CLIDEP), the only pediatric epilepsy referral center in Haiti.

Methods: A 10-year retrospective review of children consecutively assessed and treated at CLIDEP was performed. The primary outcome was seizure control following treatment for epilepsy. The secondary outcome was an accurate determination of the diagnosis of epilepsy. A data-driven principle component regression (PCR) analysis was used to identify variables associated with outcomes of interest.

Results: Of the 812 children referred for evaluation, most children (82%) underwent electroencephalography to investigate a possible epilepsy diagnosis. Very few children (7%) underwent cranial imaging. Although many patients were lost to follow-up (24%), most children who returned to clinic had less frequent seizures (51%) and compliance with medication was relatively high (79%). Using PCR, we identified a patient phenotype that was strongly associated with poor seizure control which had strong contributions from abnormal neurological examination, higher number of antiepileptic drugs, comorbid diagnoses, epileptic encephalopathy or epilepsy syndrome, and developmental delay. Head circumference also contributed to epilepsy outcomes in Haiti with smaller head sizes being associated with a poor seizure outcome. A dissociable phenotype of febrile seizures, suspected structural abnormality, epileptic encephalopathy or epilepsy syndrome, and higher seizure frequency was associated with a diagnosis of epilepsy.

Significance: We describe the current landscape of childhood epilepsy in Haiti with an emphasis on diagnosis, treatment and outcomes. The findings provide evidence for the effectiveness of programs aimed at the diagnosis and management of epilepsy in LMICs and may inform the allocation of resources and create more effective referral structures.
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http://dx.doi.org/10.1002/epi4.12384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278551PMC
June 2020

Trends in hospitalization and readmission for pediatric epilepsy and underutilization of epilepsy surgery in the United States.

Seizure 2020 Aug 17;80:263-269. Epub 2020 May 17.

Division of Pediatric Neurology, Department of Pediatrics, UCLA Medical Center, Los Angeles, CA, USA.

Background: Previous studies have shown the healthcare utilization for medically refractory epilepsy and epilepsy surgery until 2012 with disparities according to race/ethnicity and socioeconomic status. To extend these data and add other utilization information, we retrospectively investigated the nationwide trends in hospitalization and readmission during 2010-2015.

Method: We extracted data on inpatients who were diagnosed with epilepsy and those who received epilepsy surgery using the national inpatient sample and nationwide readmission database during 2010-2015. We estimated healthcare utilization related to pediatric epilepsy, the number of epilepsy surgeries, hospitalization rates and 30-day readmission rates.

Results: 100,000-120,000 children were hospitalized due to epilepsy each year. Hospitalization rates and 30-day readmission rates were 214.6-262.3 per 1000 patient-years and 72.4-78.0 per 1000 discharges, respectively. 1400-2000 children with epilepsy received epilepsy surgery, but the proportions of medically refractory epilepsy were estimated as 0.8 %-1.2 %. Disparities in patients receiving epilepsy surgery by race/ethnicity were observed during 2010-2012, but they were not after 2013. Children with higher household income levels had consistently higher proportions of receiving epilepsy surgery than those with lower levels. The hospitalization costs for epilepsy surgery were constant at $55,780-$60,813 after adjusting for healthcare cost inflation, whereas the cost for epilepsy were slightly elevated from $15,984 to $17,426.

Conclusions: We provide novel insights into the current healthcare utilization for epilepsy and epilepsy surgery. Although the disparity of epilepsy surgery seemed to be mitigated, surgery in children with medically refractory epilepsy was still underutilized.
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http://dx.doi.org/10.1016/j.seizure.2020.05.013DOI Listing
August 2020

Pilot Study of Neurodevelopmental Impact of Early Epilepsy Surgery in Tuberous Sclerosis Complex.

Pediatr Neurol 2020 08 14;109:39-46. Epub 2020 Apr 14.

Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama. Electronic address:

Background: To determine if early epilepsy surgery mitigates detrimental effects of refractory epilepsy on development, we investigated surgical and neurodevelopmental outcomes in children with tuberous sclerosis complex who underwent surgery before age two years.

Methods: Prospective multicenter observational study of 160 children with tuberous sclerosis complex. Surgical outcome was determined for the seizure type targeted by surgery. We obtained Vineland Adaptive Behavior Scales, Second Edition (Vineland-II); Mullen Scales of Early Learning; and Preschool Language Scales, Fifth Edition, at age three, six, nine, 12, 18, 24, and 36 months. Surgical cases were compared with children without seizures, with controlled seizures, and with medically refractory seizures.

Results: Nineteen children underwent surgery (median age 17 months, range 3.7 to 21.3), and mean follow-up was 22.8 months (range 12 to 48). Surgical outcomes were favorable in 12 (63%, Engel I-II) and poor in seven (37%, Engel III-IV). Nine (47%) had new or ongoing seizures distinct from those surgically targeted. All children with seizures demonstrated longitudinal decline or attenuated gains in neurodevelopment, the surgical group scoring the lowest. Favorable surgical outcome was associated with increased Mullen Scales of Early Learning receptive and expressive language subscores compared with the medically refractory seizure group. A nonsignificant but consistent pattern of improvement with surgery was seen in all tested domains.

Conclusions: These pilot data show neurodevelopmental gains in some domains following epilepsy surgery. A properly powered, prospective multicenter observational study of early epilepsy surgery is needed, using both surgical and developmental outcome metrics.
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http://dx.doi.org/10.1016/j.pediatrneurol.2020.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387194PMC
August 2020

Magnetic resonance-guided stereotactic laser ablation therapy for the treatment of pediatric brain tumors: a multiinstitutional retrospective study.

J Neurosurg Pediatr 2020 Mar 27:1-9. Epub 2020 Mar 27.

Departments of7Neurosurgery and.

Objective: This study aimed to assess the safety and efficacy of MR-guided stereotactic laser ablation (SLA) therapy in the treatment of pediatric brain tumors.

Methods: Data from 17 North American centers were retrospectively reviewed. Clinical, technical, and radiographic data for pediatric patients treated with SLA for a diagnosis of brain tumor from 2008 to 2016 were collected and analyzed.

Results: A total of 86 patients (mean age 12.2 ± 4.5 years) with 76 low-grade (I or II) and 10 high-grade (III or IV) tumors were included. Tumor location included lobar (38.4%), deep (45.3%), and cerebellar (16.3%) compartments. The mean follow-up time was 24 months (median 18 months, range 3-72 months). At the last follow-up, the volume of SLA-treated tumors had decreased in 80.6% of patients with follow-up data. Patients with high-grade tumors were more likely to have an unchanged or larger tumor size after SLA treatment than those with low-grade tumors (OR 7.49, p = 0.0364). Subsequent surgery and adjuvant treatment were not required after SLA treatment in 90.4% and 86.7% of patients, respectively. Patients with high-grade tumors were more likely to receive subsequent surgery (OR 2.25, p = 0.4957) and adjuvant treatment (OR 3.77, p = 0.1711) after SLA therapy, without reaching significance. A total of 29 acute complications in 23 patients were reported and included malpositioned catheters (n = 3), intracranial hemorrhages (n = 2), transient neurological deficits (n = 11), permanent neurological deficits (n = 5), symptomatic perilesional edema (n = 2), hydrocephalus (n = 4), and death (n = 2). On long-term follow-up, 3 patients were reported to have worsened neuropsychological test results. Pre-SLA tumor volume, tumor location, number of laser trajectories, and number of lesions created did not result in a significantly increased risk of complications; however, the odds of complications increased by 14% (OR 1.14, p = 0.0159) with every 1-cm3 increase in the volume of the lesion created.

Conclusions: SLA is an effective, minimally invasive treatment option for pediatric brain tumors, although it is not without risks. Limiting the volume of the generated thermal lesion may help decrease the incidence of complications.
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http://dx.doi.org/10.3171/2020.1.PEDS19496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885863PMC
March 2020

Interest and participation in global neurosurgery: a survey of Canadian neurosurgery residents.

Neurosurg Focus 2020 03;48(3):E21

1Division of Neurosurgery, Department of Surgery, University of Montreal.

Objective: The lack of access to primary neurosurgical care presents a significant burden for patients in low- and middle-income countries (LMICs). Efforts to decrease the inequities in access to surgical care have become an increasing focus of initiatives and advocacy within the international neurosurgery community. Although residents may represent highly active members of international teams, the extent of their availability for and interest in global neurosurgery opportunities remains unclear. The objectives of this study were to assess the degree of participation, the level of interest, and the perceived barriers for residents of Canadian neurosurgery programs in engaging in neurosurgery initiatives in LMICs.

Methods: A cross-sectional survey was administered to 144 residents from all accredited Canadian neurosurgery residency programs. The survey was used to determine the level of participation and interest in global neurosurgery initiatives.

Results: The survey response rate from residents at Canadian neurosurgery programs was 45/144 (31%), although not all respondents answered every question; thus, the denominator for each question is not always 45. Most neurosurgery residents (n = 30, 68%) were unaware of any global neurosurgery opportunities available during residency. Despite 64% of residents having an interest in participation (strongly agree/agree; n = 28), with most residents planning on participating as attending staff (strongly agree/agree; n = 28, 64%), only 3 residents (7%) had taken part in LMIC neurosurgery initiatives. The most cited perceived limitations for participation were lack of time (n = 37, 84%) and finances (n = 26, 59%).

Conclusions: Among surveyed residents from Canadian neurosurgery programs, there was a low participation rate in global neurosurgery initiatives and limited knowledge of available opportunities, despite relatively high interest. Many respondents identified time and financial constraints as barriers to participation. Many residents felt that interest could increase were there a structured program dedicated to global neurosurgery available in their residency program.
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http://dx.doi.org/10.3171/2019.12.FOCUS19767DOI Listing
March 2020

Surgical management of pediatric patients with encephalopathy due to electrical status epilepticus during sleep (ESES).

Epileptic Disord 2020 Feb;22(1):39-54

Division of Pediatric Neurology, Nicklaus Children's Hospital, Miami, USA.

ESES is a developmental epileptic disorder directly responsible for progressive encephalopathy and neurocognitive regression. The natural history, indications for surgical intervention, and predictors for favorable seizure and neuropsychological outcome remain unclear. We performed a retrospective review of children who underwent resective or disconnective surgery for ESES between January 2009 and July 2016 at a large tertiary pediatric center. Information on the patients' demographics, seizure semiology, radiographic and electrographic findings, and surgical management was collected. The primary outcome was seizure freedom at last follow-up visit, and secondary outcomes were neuropsychological improvement and electrographic ESES resolution. We identified 11 children who underwent surgery for ESES. The mean ages were 3.2 years for seizure onset, 7.1 years for formal ESES diagnosis, and 9.4 years for surgery. Seizure etiologies included cortical malformations (four patients), encephalomalacia and gliosis from prior hemorrhage or tumor resections (three patients), developmental porencephaly (one patient), and Rasmussen's encephalitis (one patient); the etiology was unknown in two children. Preoperatively, nine children had motor deficits, seven had speech and language delay, and three had visual field defects. All children had seizures and neuropsychological regression prior to surgical consideration. Focal cortical resections were performed in seven children, and hemispherectomies in four. Post-operatively, nine children experienced decreased seizure frequency, eight had neuropsychological improvement, and nine had resolution of electrographic ESES. Patients with poor surgical outcomes had more significant pre-operative comorbidities, in addition to bilateral ESES activity. In this case series, surgery for a carefully selected group of children with ESES is safe and feasible, yielding rates of seizure freedom and neuropsychological improvement that compare favorably with previous reports for antiepileptic drugs, benzodiazepines, and steroids. As we gain greater understanding into the management of ESES, surgery is an increasingly useful tool for patients with mild or moderate neurodevelopmental delay, focal epileptogenic foci, and hemi-ESES electrographic findings.
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http://dx.doi.org/10.1684/epd.2020.1129DOI Listing
February 2020

Seizure outcomes in children with Rasmussen's encephalitis undergoing resective or hemispheric epilepsy surgery: an individual participant data meta-analysis.

J Neurosurg Pediatr 2019 Dec 6:1-10. Epub 2019 Dec 6.

2Department of Neurosurgery, University of California, Los Angeles, California.

Objective: 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.

Methods: 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).

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.3171/2019.9.PEDS19380DOI Listing
December 2019

Pathological high frequency oscillations associate with increased GABA synaptic activity in pediatric epilepsy surgery patients.

Neurobiol Dis 2020 02 17;134:104618. Epub 2019 Oct 17.

Division of Pediatric Neurology, Mattel Children's Hospital, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.

Pathological high-frequency oscillations (HFOs), specifically fast ripples (FRs, >250 Hz), are pathognomonic of an active epileptogenic zone. However, the origin of FRs remains unknown. Here we explored the correlation between FRs recorded with intraoperative pre-resection electrocorticography (ECoG) and spontaneous synaptic activity recorded ex vivo from cortical tissue samples resected for the treatment of pharmacoresistant epilepsy. The cohort included 47 children (ages 0.22-9.99 yr) with focal cortical dysplasias (CD types I and II), tuberous sclerosis complex (TSC) and non-CD pathologies. Whole-cell patch clamp recordings were obtained from pyramidal neurons and interneurons in cortical regions that were positive or negative for pathological HFOs, defined as FR band oscillations (250-500 Hz) at ECoG. The frequency of spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and IPSCs, respectively) was compared between HFO+ and HFO- regions. Regardless of pathological substrate, regions positive for FRs displayed significantly increased frequencies of sIPSCs compared with regions negative for FRs. In contrast, the frequency of sEPSCs was similar in both regions. In about one third of cases (n = 17), pacemaker GABA synaptic activity (PGA) was observed. In the vast majority (n = 15), PGA occurred in HFO+ areas. Further, fast-spiking interneurons displayed signs of hyperexcitability exclusively in HFO+ areas. These results indicate that, in pediatric epilepsy patients, increased GABA synaptic activity is associated with interictal FRs in the epileptogenic zone and suggest an active role of GABAergic interneurons in the generation of pathological HFOs. Increased GABA synaptic activity could serve to dampen excessive excitability of cortical pyramidal neurons in the epileptogenic zone, but it could also promote neuronal network synchrony.
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http://dx.doi.org/10.1016/j.nbd.2019.104618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980668PMC
February 2020

Systematic review of spinal deformities following multi-level selective dorsal rhizotomy.

Childs Nerv Syst 2020 05 8;36(5):1025-1035. Epub 2019 Oct 8.

Division of Neurosurgery, Children's Hospital of Eastern Ontario, Rm 3359 CHEO, 401 Smyth Ave, Ottawa, ON, K1H 8L1, Canada.

Purpose: Cerebral palsy is a common neurological disorder that involves spasticity of the extremities and can lead to lifelong disability. Selective dorsal rhizotomy (SDR) can improve spasticity and quality of life in these patients, but it may be associated with the development of spinal deformity. Risk factors for spinal deformity after SDR have not yet been systematically examined.

Methods: Medline, Embase, and Web of Science databases were queried for clinical studies reporting incidence of new or worsening spinal deformity, including scoliosis, after SDR. Variables that represent possible risk factors for deformity were correlated with reported incidence of deformity.

Results: Twenty-two articles for a total of 1485 patients met the inclusion criteria for this study. Deformity occurs among all patients with a weighted mean incidence of 28.0%. Scoliosis appears to be the most common deformity occurring with a weighted mean incidence of 31.6%. There is substantial heterogeneity between studies, limiting our analysis. Significant positive correlation was found between percent of patients that developed any type of deformity and the ratio of female to male patients, p = 0.02. Significant positive correlation was also found between percent of patients that develop scoliosis and the ratio of female to male patients, p < 0.01, and between scoliosis and the number of years to follow-up, p < 0.01.

Conclusion: Spinal deformity is an important potential complication of SDR with scoliosis being the most common type of deformity. The major risk factor for postoperative deformity is female sex. Deformity was also found to significantly increase with extended follow-up, indicating a slow process that should be carefully monitored.
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http://dx.doi.org/10.1007/s00381-019-04375-xDOI Listing
May 2020

Prospective observational study: Fast ripple localization delineates the epileptogenic zone.

Clin Neurophysiol 2019 11 17;130(11):2144-2152. Epub 2019 Sep 17.

Division of Pediatric Neurology, Department of Pediatrics, UCLA Mattel Children's Hospital, David Geffen School of Medicine, Los Angeles, CA, USA.

Objective: To investigate spatial correlation between interictal HFOs and neuroimaging abnormalities, and to determine if complete removal of prospectively identified interictal HFOs correlates with post-surgical seizure-freedom.

Methods: Interictal fast ripples (FRs: 250-500 Hz) in 19 consecutive children with pharmacoresistant focal epilepsy who underwent extra-operative electrocorticography (ECoG) recording were prospectively analyzed. The interictal FRs were sampled at 2000 Hz and were visually identified during 10 min of slow wave sleep. Interictal FRs, MRI and FDG-PET were delineated on patient-specific reconstructed three-dimensional brain MRI.

Results: Interictal FRs were observed in all patients except one. Thirteen out of 18 patients (72%) exhibited FRs beyond the extent of neuroimaging abnormalities. Fifteen of 19 children underwent resective surgery, and survival analysis with log-rank test demonstrated that complete resection of cortical sites showing interictal FRs correlated with longer post-operative seizure-freedom (p < 0.01). Complete resection of seizure onset zones (SOZ) also correlated with longer post-operative seizure-freedom (p = 0.01), yet complete resection of neuroimaging abnormalities did not (p = 0.43).

Conclusions: Prospective visual analysis of interictal FRs was feasible, and it seemed to accurately localize epileptogenic zones.

Significance: Topological extent of epileptogenic region may exceed what is discernible by multimodal neuroimaging.
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http://dx.doi.org/10.1016/j.clinph.2019.08.026DOI Listing
November 2019

Survival of infants ≤24 months of age with brain tumors: A population-based study using the SEER database.

PLoS One 2019 25;14(9):e0223051. Epub 2019 Sep 25.

Division of Neurosurgery, Children's Hospital of Eastern Ontario, ON, Canada.

Introduction: Brain tumors are the most common solid malignancy and leading cause of cancer-related deaths in infants. Current epidemiological data is limited by low numbers of reported cases. This study used a population-based approach with analysis of contemporary and historical survival curves to provide up-to-date prognostication.

Methods: Observational cohort analysis was performed using the Surveillance, Epidemiology and End Results (SEER) database. Infants with brain tumors diagnosed from 1973 to 2013 were categorized by the most common tumor types (diffuse astrocytic and oligodendroglioma, choroid plexus, embryonal, ependymal, medulloblastoma and pilocytic astrocytoma). The 1, 5 and 10 year survival was stratified by decade, with trends in management and outcomes analyzed.

Results: We identified 2996 affected infants satisfying inclusion criteria. All tumor types, except embryonal and choroid plexus, demonstrated improving survival with time. Infants with embryonal tumors showed a decline in survival from the 1970s to 1990s (p = 0.009), whereas infants with choroid plexus tumors had no change in survival. Infants with ependymal tumors experienced the greatest improvement in survival from 1980s to 1990s and 1990s to 2000s (p = 0.0001, p = 0.01), with 5-year survival probability improving from 28% (95% CI 15-42%) in the 1980s to 77% (95% CI 69-83%) the 2000s. The use of radiation declined from 1970 to 2000 for all tumors; however, radiation treatment for embryonal and ependymal subtypes increased after 2000.

Conclusions: While overall survival for infants with brain tumors has improved from the 1970s onwards, not every tumor type has seen a statistically significant change. Given changes in management and survival, prognostication of infants with brain tumor should be updated.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223051PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760899PMC
March 2020

Evidence for Innate and Adaptive Immune Responses in a Cohort of Intractable Pediatric Epilepsy Surgery Patients.

Front Immunol 2019 29;10:121. Epub 2019 Jan 29.

Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.

Brain-infiltrating lymphocytes (BILs) were isolated from resected brain tissue from 10 pediatric epilepsy patients who had undergone surgery for Hemimegalencephaly (HME) ( = 1), Tuberous sclerosis complex (TSC) ( = 2), Focal cortical dysplasia (FCD) ( = 4), and Rasmussen encephalitis (RE) ( = 3). Peripheral blood mononuclear cells (PBMCs) were also isolated from blood collected at the time of the surgery. Cells were immunostained with a panel of 20 antibody markers, and analyzed by mass cytometry. To identify and quantify the immune cell types in the samples, an unbiased clustering method was applied to the entire data set. More than 85 percent of the CD45 cells isolated from resected RE brain tissue comprised T cells; by contrast NK cells and myeloid cells constituted 80-95 percent of the CD45 cells isolated from the TSC and the FCD brain specimens. Three populations of myeloid cells made up >50 percent of all of the myeloid cells in all of the samples of which a population of HLA-DR CD11b CD4 cells comprised the vast majority of myeloid cells in the BIL fractions from the FCD and TSC cases. CD45RA HLA-DR CD11b CD16 NK cells constituted the major population of NK cells in the blood from all of the cases. This subset also comprised the majority of NK cells in BILs from the resected RE and HME brain tissue, whereas NK cells defined as CD45RA HLA-DR CD11b CD16 cells comprised 86-96 percent of the NK cells isolated from the FCD and TSC brain tissue. Thirteen different subsets of CD4 and CD8 αβ T cells and γδ T cells accounted for over 80% of the CD3 T cells in all of the BIL and PBMC samples. At least 90 percent of the T cells in the RE BILs, 80 percent of the T cells in the HME BILs and 40-66 percent in the TSC and FCD BILs comprised activated antigen-experienced (CD45RO HLA-DR CD69) T cells. We conclude that even in cases where there is no evidence for an infection or an immune disorder, activated peripheral immune cells may be present in epileptogenic areas of the brain, possibly in response to seizure-driven brain inflammation.
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http://dx.doi.org/10.3389/fimmu.2019.00121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362260PMC
January 2020

Cellular antiseizure mechanisms of everolimus in pediatric tuberous sclerosis complex, cortical dysplasia, and non-mTOR-mediated etiologies.

Epilepsia Open 2018 Dec 2;3(Suppl Suppl 2):180-190. Epub 2018 Sep 2.

Division of Pediatric Neurology Mattel Children's Hospital David Geffen School of Medicine at University of California Los Angeles Los Angeles California U.S.A.

The present study was designed to examine the potential cellular antiseizure mechanisms of everolimus, a mechanistic target of rapamycin (mTOR) pathway blocker, in pediatric epilepsy cases. Cortical tissue samples obtained from pediatric patients (n = 11, ages 0.67-6.75 years) undergoing surgical resections for the treatment of their pharmacoresistant epilepsy were examined electrophysiologically in ex vivo slices. The cohort included mTOR-mediated pathologies (tuberous sclerosis complex [TSC] and severe cortical dysplasia [CD]) as well as non-mTOR-mediated pathologies (tumor and perinatal infarct). Bath application of everolimus (2 μm) had practically no effect on spontaneous inhibitory postsynaptic activity. In contrast, long-term application of everolimus reduced spontaneous excitatory postsynaptic activity, burst discharges induced by blockade of γ-aminobutyric acid A (GABA) receptors, and epileptiform activity generated by 4-aminopyridine, a K channel blocker. The antiseizure effects were more pronounced in TSC and CD cases, whereas in non-mTOR-mediated pathologies, the effects were subtle at best. These results support further clinical trials of everolimus in mTOR pathway-mediated pathologies and emphasize that the effects require sustained exposure over time.
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http://dx.doi.org/10.1002/epi4.12253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6293070PMC
December 2018

Interrater reliability in visual identification of interictal high-frequency oscillations on electrocorticography and scalp EEG.

Epilepsia Open 2018 Dec 2;3(Suppl Suppl 2):127-132. Epub 2018 Nov 2.

Division of Pediatric Neurology UCLA Mattel Children's Hospital David Geffen School of Medicine Los Angeles California U.S.A.

High-frequency oscillations (HFOs), including ripples (Rs) and fast ripples (FRs), are promising biomarkers of epileptogenesis, but their clinical utility is limited by the lack of a standardized approach to identification. We set out to determine whether electroencephalographers experienced in HFO analysis can reliably identify and quantify interictal HFOs. Two blinded raters independently reviewed 10 intraoperative electrocorticography (ECoG) samples from epilepsy surgery cases, and 10 scalp EEG samples from epilepsy monitoring unit evaluations. HFOs were visually marked using bandpass filters (R, 80-250 Hz; FR, 250-500 Hz) with a sampling frequency of 2,000 Hz. There was agreement as to the presence or absence of epileptiform discharges (EDs), Rs, and FRs, in 17, 18, and 18 cases, respectively. Interrater reliability (IRR) was favorable with κ = 0.70, 0.80, and 0.80, respectively, and similar for ECoG and scalp electroencephalography (EEG). Furthermore, interclass correlation for rates of Rs (0.99, 95% confidence interval [CI] 0.96-0.99) and FRs (0.77, 95% CI 0.41-0.91) were superior in comparison to EDs (0.37, 95% CI -0.60 to 0.75). Our data suggest that HFO identification and quantification are reliable among experienced electroencephalographers. Our findings support the reliability of utilizing HFO data in both research and clinical arenas.
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http://dx.doi.org/10.1002/epi4.12266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6293061PMC
December 2018

Deep brain stimulation for Gilles de la Tourette syndrome in children and youth: a meta-analysis with individual participant data.

J Neurosurg Pediatr 2018 10;23(2):236-246

Department of Surgery, University of Toronto.

Objective: Gilles de la Tourette syndrome (GTS) is a disorder characterized by motor and vocal tics. Although by definition the onset of GTS is before age 18 years, clinical trials of deep brain stimulation (DBS) have been conducted only in adults. Using individual participant data (IPD) meta-analysis methodology, the current study investigated the safety and efficacy of DBS as a treatment for GTS in children and youth.

Methods: A systematic review with no date or language restrictions was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Three electronic databases were searched: PubMed, EMBASE, and Web of Science. From 843 articles screened, the IPD of 58 children and youth (ages 12–21 years) extracted from 21 articles were collected and analyzed. A mixed-effects univariable analysis followed by multivariable hierarchical regression was performed using change in the Yale Global Tic Severity Scale (YGTSS) score as the primary outcome and reported measures of comorbidities as secondary outcomes.

Results: The authors’ results showed an average improvement of 57.5% ± 24.6% across studies on the YGTSS. They also found that comorbid depression and stimulation pulse width each correlated negatively with outcome (p < 0.05). In patients with less severe GTS, greater improvements were evident following thalamic stimulation. More than one-quarter (n = 16, 27.6%) of participants experienced side effects, the majority of which were minor.

Conclusions: DBS in the pediatric population may be an effective option with a moderate safety profile for treatment of GTS in carefully selected children and youth. Large, prospective studies with long-term follow-up are necessary to understand how DBS influences tic symptoms and may alter the natural course of GTS in children.
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http://dx.doi.org/10.3171/2018.7.PEDS18300DOI Listing
October 2018

Surgical outcomes for medically intractable epilepsy in low- and middle-income countries: a systematic review and meta-analysis.

J Neurosurg 2018 Nov 1:1-11. Epub 2018 Nov 1.

9Division of Neurosurgery, The Hospital for Sick Children, Department of Surgery, University of Toronto, Ontario.

OBJECTIVEThe aim of this study was to describe the current state of epilepsy surgery and establish estimates of seizure outcomes following surgery for medically intractable epilepsy (MIE) in low- and middle-income countries (LMICs).METHODSThe MEDLINE and Embase databases were searched without publication date restriction. This search was supplemented by a manual screen of key epilepsy and neurosurgical journals (January 2005 to December 2016). Studies that reported outcomes for at least 10 patients of any age undergoing surgery for MIE in LMICs over a defined follow-up period were included. A meta-analysis with a random-effects model was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines. Pooled estimates of seizure freedom and favorable seizure outcomes following anterior temporal lobectomy with or without amygdalohippocampectomy (ATL ± AH) were reported.RESULTSTwenty studies were selected, of which 16 were from Asian centers. The average age at surgery in all studies was less than 30 years, and the average preoperative duration of epilepsy ranged from 3 to 16.1 years. Mesial temporal sclerosis accounted for 437 of 951 described pathologies, and 1294 of the 1773 procedures were ATL ± AH. Based on 7 studies (646 patients) the pooled seizure freedom estimate following ATL ± AH was 68% (95% CI 55%-82%). Based on 8 studies (1096 patients), the pooled estimate for favorable seizure outcomes was 79% (95% CI 74%-85%).CONCLUSIONSSurgery for MIE in LMICs shows a high percentage of seizure freedom and favorable outcomes. These findings call for a concerted global effort to improve timely access to surgery for MIE patients in these regions, including investments aimed at refining existing and establishing additional centers.
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http://dx.doi.org/10.3171/2018.5.JNS18599DOI Listing
November 2018

Presurgical hyperconnectivity of the ablation volume is associated with seizure-freedom after magnetic resonance-guided laser interstitial thermal therapy.

Seizure 2018 Oct 9;61:89-93. Epub 2018 Aug 9.

Department of Radiology/Diagnostic Imaging, Nicklaus Children's Hospital, Miami, FL, USA.

Purpose: Magnetic Resonance-guided Laser Interstitial Thermal Therapy (MRgLITT) is an emerging minimally-invasive alternative to resective surgery for medically-intractable epilepsy. The precise lesioning effect produced by MRgLITT supplies opportunities to glean insights into epileptogenic regions and their interactions with functional brain networks. In this exploratory analysis, we sought to characterize associations between MRgLITT ablation zones and large-scale brain networks that portended seizure outcome using resting-state fMRI.

Methods: Presurgical fMRI and intraoperatively volumetric structural imaging were obtained, from which the ablation volume was segmented. The network properties of the ablation volume within the brain's large-scale brain networks were characterized using graph theory and compared between children who were and were not rendered seizure-free.

Results: Of the seventeen included children, five achieved seizure freedom following MRgLITT. Greater functional connectivity of the ablation volume to canonical resting-state networks was associated with seizure-freedom (p < 0.05, FDR-corrected). The ablated volume in children who subsequently became seizure-free following MRgLITT had significantly greater strength, and eigenvector centrality within the large-scale brain network.

Conclusions: These findings provide novel insights into the interaction between epileptogenic cortex and large-scale brain networks. The association between ablation volume and resting-state networks may supply novel avenues for presurgical planning and patient stratification.
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http://dx.doi.org/10.1016/j.seizure.2018.08.006DOI Listing
October 2018