24 results on '"Mathern GW"'
Search Results
2. Improved outcomes in pediatric epilepsy surgery: the UCLA experience, 1986-2008.
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Hemb M, Velasco TR, Parnes MS, Wu JY, Lerner JT, Matsumoto JH, Yudovin S, Shields WD, Sankar R, Salamon N, Vinters HV, Mathern GW, Hemb, M, Velasco, T R, Parnes, M S, Wu, J Y, Lerner, J T, Matsumoto, J H, Yudovin, S, and Shields, W D
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- 2010
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3. Noninvasive testing, early surgery, and seizure freedom in tuberous sclerosis complex.
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Wu JY, Salamon N, Kirsch HE, Mantle MM, Nagarajan SS, Kurelowech L, Aung MH, Sankar R, Shields WD, Mathern GW, Wu, J Y, Salamon, N, Kirsch, H E, Mantle, M M, Nagarajan, S S, Kurelowech, L, Aung, M H, Sankar, R, Shields, W D, and Mathern, G W
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- 2010
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4. Vagus nerve stimulation for essential tremor: a pilot efficacy and safety trial.
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Handforth A, Ondo WG, Tatter S, Mathern GW, Simpson RK Jr., Walker F, Sutton JP, Hubble JP, Jankovic J, Handforth, A, Ondo, W G, Tatter, S, Mathern, G W, Simpson, R K Jr, Walker, F, Sutton, J P, Hubble, J P, and Jankovic, J
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- 2003
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5. Cerebral hemispherectomy: When half a brain is good enough.
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Mathern GW
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- 2010
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6. Magnetic source imaging localizes epileptogenic zone in children with tuberous sclerosis complex.
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Wu JY, Sutherling WW, Koh S, Salamon N, Jonas R, Yudovin S, Sankar R, Shields WD, and Mathern GW
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- 2006
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7. Web-based eight-question tool to determine epilepsy surgery evaluation: The future is here.
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Langfitt JT and Mathern GW
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- 2012
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8. Epilepsy surgery patients with cortical dysplasia: Present and future therapeutic challenges.
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Mathern GW
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- 2009
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9. Childhood-onset temporal lobe epilepsy: neuroimaging predicts seizure control.
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Mathern GW and Trevathan E
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- 2006
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10. Mechanisms of epileptogenicity in cortical dysplasias.
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Najm I, Ying Z, Babb T, Crino PB, Macdonald R, Mathern GW, Spreafico R, Najm, I, Ying, Z, Babb, T, Crino, P B, Macdonald, R, Mathern, G W, and Spreafico, R
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- 2004
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11. Long-Term Patient-Reported Outcomes of Visual Field Defects and Compensatory Mechanisms in Patients After Cerebral Hemispherectomy.
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Meer EA, Chen MF, Jones M, Mathern GW, and Pineles SL
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- Adolescent, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Male, Postoperative Complications physiopathology, Scotoma physiopathology, Time Factors, Visual Field Tests, Hemispherectomy adverse effects, Patient Reported Outcome Measures, Postoperative Complications etiology, Scotoma etiology, Seizures surgery, Visual Acuity, Visual Fields physiology
- Abstract
Background: In cases of intractable epilepsy resistant to drug therapy, hemispherectomy is often the only treatment option to mitigate seizures; however, the true long-term subjective visual outcomes are relatively unexplored. In this study, we sought to determine and characterize patient-reported visual function years after hemispherectomy., Methods: This was an observational study conducted on a large cohort of children with seizure disorder treated with cerebral hemispherectomy. An online survey was sent to parents with questions to assess subjective visual function with a variety of questions from presence of visual field defects after hemispherectomy, to improvement over time, compensatory mechanisms used, and development of strabismus., Results: This survey was emailed to 248 parents of previously evaluated children who agreed to be re-surveyed, 48 (20%) of which responded. The average age at hemispherectomy was approximately 5 (±4) years, and the average time after hemispherectomy was 7 (±5) years. Thirty-nine patients (81%) were seizure-free after 1 surgery and 85% (n = 41) were seizure-free after ≥1 surgeries. Thirty-four (71%) experienced a visual field defect after surgery, but 25 (52%) experienced subjective improvement over time. Thirty-eight (79%) used compensatory mechanisms, such as head tilting, with 16 (33%) patients experiencing subjective improvement over time. Twenty-seven (56%) patients experienced a decrease in visual acuity after surgery with 12 (25%) experiencing subjective improvement over time., Conclusion: In a large cohort examining patient-reported visual outcomes years after hemispherectomy, most patients experienced strabismus and/or visual field defects. However, more than half reported improvements and compensatory mechanisms (exotropic strabismus and ipsilateral esotropic strabismus) over time, presumably to enhance visual field function. By exploring subjective visual and cognitive function, this paper uniquely characterizes patient-reported improvements over time, and provides motivation for larger longitudinal studies using more quantitative measures of visual function and improvement after hemispherectomy., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by North American Neuro-Ophthalmology Society.)
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- 2021
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12. Removing high-frequency oscillations: A prospective multicenter study on seizure outcome.
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Jacobs J, Wu JY, Perucca P, Zelmann R, Mader M, Dubeau F, Mathern GW, Schulze-Bonhage A, and Gotman J
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- Adolescent, Adult, Child, Child, Preschool, Electrocorticography, Electroencephalography, Female, Humans, Infant, Male, Middle Aged, Prospective Studies, Treatment Outcome, Young Adult, Brain Waves physiology, Neurosurgical Procedures methods, Seizures physiopathology, Seizures surgery
- Abstract
Objective: To evaluate the use of interictal high-frequency oscillations (HFOs) in epilepsy surgery for prediction of postsurgical seizure outcome in a prospective multicenter trial., Methods: We hypothesized that a seizure-free outcome could be expected in patients in whom the surgical planning included the majority of HFO-generating brain tissue while a poor seizure outcome could be expected in patients in whom only a few such areas were planned to be resected. Fifty-two patients were included from 3 tertiary epilepsy centers during a 1-year period. Ripples (80-250 Hz) and fast ripples (250-500 Hz) were automatically detected during slow-wave sleep with chronic intracranial EEG in 2 centers and acute intraoperative electrocorticography in 1 patient., Results: There was a correlation between the removal of HFO-generating regions and seizure-free outcome at the group level for all patients. No correlation was found, however, for the center-specific analysis, and an individual prognostication of seizure outcome was true in only 36 patients (67%). Moreover, some patients became seizure-free without removal of the majority of HFO-generating tissue. The investigation of influencing factors, including comparisons of visual and automatic analysis, using a threshold analysis for areas with high HFO activity, and excluding contacts bordering the resection, did not result in improved prognostication., Conclusions: On an individual patient level, a prediction of outcome was not possible in all patients. This may be due to the analysis techniques used. Alternatively, HFOs may be less specific for epileptic tissue than earlier studies have indicated., (© 2018 American Academy of Neurology.)
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- 2018
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13. Knowledge translation of an online tool to determine candidacy for epilepsy surgery evaluation.
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Sauro KM, Holroyd-Leduc J, Wiebe S, Quan H, Cooke L, Cross JH, Mathern GW, Armson H, Stromer J, and Jetté N
- Abstract
Background: Guidelines recommend that surgery be considered in patients with drug-resistant epilepsy, yet delays to epilepsy surgery still exist. A Web-based, evidence-informed clinical decision tool (www.toolsforepilepsy.com) was developed to help physicians determine which patients are appropriate for an epilepsy surgery evaluation. We evaluated the usability and feasibility of the tool with the intended end users in order to improve implementation into practice., Methods: Usability testing was conducted with relevant end users. After the tool was modified based on usability results, another group of end users trialed the tool in their clinical practice. This latter group of end users then participated in focus groups and semi-structured interviews to address barriers and facilitators to tool implementation. Finally, a stakeholder meeting was held with domain experts and end users to discuss further changes to the tool and implementation strategies., Results: Six overall themes were identified through usability testing, and an additional 11 themes were identified through the focus groups and interviews. The tool was modified based on these findings, which were then presented at the stakeholder meeting of experts and end users for further refinement. The findings were also used to guide discussions of potential implementation strategies at the meeting., Conclusion: This study provides guidance on how to improve the usability of clinical decision tools by engaging end users, experts, and other key stakeholders. The modifications to the tool should facilitate its implementation in clinical practice and ultimately enhance the quality of care persons with epilepsy receive.
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- 2016
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14. DTI of tuber and perituberal tissue can predict epileptogenicity in tuberous sclerosis complex.
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Yogi A, Hirata Y, Karavaeva E, Harris RJ, Wu JY, Yudovin SL, Linetsky M, Mathern GW, Ellingson BM, and Salamon N
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- Adolescent, Child, Child, Preschool, Epilepsy epidemiology, Female, Humans, Infant, Male, Retrospective Studies, Tuberous Sclerosis epidemiology, Young Adult, Diffusion Tensor Imaging methods, Epilepsy diagnosis, Epilepsy metabolism, Tuberous Sclerosis diagnosis, Tuberous Sclerosis metabolism
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Objective: To evaluate whether diffusion tensor imaging (DTI) can predict epileptogenic tubers by measuring apparent diffusion coefficient (ADC), fractional anisotropy, axial diffusivity, and radial diffusivity in both tubers and perituberal tissue in pediatric patients with tuberous sclerosis complex (TSC) undergoing epilepsy surgery., Methods: We retrospectively selected 23 consecutive patients (aged 0.4-19.6 years, mean age of 5.2; 13 female, 10 male) who underwent presurgical DTI and subsequent surgical resection between 2004 and 2013 from the University of California-Los Angeles TSC Clinic. We evaluated presurgical examinations including video-EEG, brain MRI, (18)F-fluorodeoxyglucose-PET, magnetic source imaging, and intraoperative electrocorticography for determining epileptogenic tubers. A total of 545 tubers, 33 epileptogenic and 512 nonepileptogenic, were identified. Two observers generated the regions of interest (ROIs) of tubers (ROI(tuber)), the 4-mm-thick ring-shaped ROIs surrounding the tubers (ROI(perituber)), and the combined ROIs (ROI(tuber+perituber)) in consensus and calculated maximum, minimum, mean, and median values of each DTI measure in each ROI for all tubers., Results: The Mann-Whitney U test demonstrated that the epileptogenic group showed higher maximum ADC and radial diffusivity values in all ROIs, and that maximum ADC in ROI(tuber+perituber) showed the strongest difference (p = 0.001). Receiver operating characteristic analysis demonstrated that maximum ADC measurements in ROI(tuber+perituber) (area under curve = 0.68 ± 0.05, p < 0.001) had 81% sensitivity and 44% specificity for correctly identifying epileptogenic tubers with a cutoff value of 1.32 μm(2)/ms., Conclusions: DTI analysis of tubers and perituberal tissue may help to identify epileptogenic tubers in presurgical patients with TSC more easily and effectively than current invasive methods., (© 2015 American Academy of Neurology.)
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- 2015
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15. Who's responsible to refer for epilepsy surgery? We all are!
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Jehi L and Mathern GW
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- Female, Humans, Male, Attitude of Health Personnel, Clinical Competence, Epilepsy surgery, Neurology, Neurosurgical Procedures
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- 2015
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16. Outcomes for temporal lobe epilepsy operations may not be equal: a call for an RCT of ATL vs SAH.
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Mathern GW and Miller JW
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- Humans, Amygdala surgery, Anterior Temporal Lobectomy methods, Epilepsy, Temporal Lobe surgery, Hippocampus surgery, Temporal Lobe surgery
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- 2013
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17. Hemimegalencephaly, a paradigm for somatic postzygotic neurodevelopmental disorders.
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Baek ST, Gibbs EM, Gleeson JG, and Mathern GW
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- Humans, Malformations of Cortical Development embryology, Malformations of Cortical Development pathology, Malformations of Cortical Development genetics
- Abstract
Purpose of Review: Combining human genomics and molecular biology, recent studies have made pivotal progress toward understanding the cause of hemimegalencephaly (HME) and other cerebral megalencephaly syndromes. The present article highlights recent advances of the genetic cause of these conditions, and considers the role of somatic postzygotic genetic lesions in brain maldevelopment., Recent Findings: Studies over the past 12 months have identified de-novo somatic mutations as one possible cause in HME. The gene mutations involve components of the phosphatidylinositol 3-kinase (PI3K)-AKT (also known as protein kinase B)-mammalian target of rapamycin (mTOR) pathway and include PIK3CA, PIK3R2, AKT3, and MTOR. These mutations were identified by comparing genomic data obtained from surgically resected brain tissue with nondiseased tissue, and by single-neuron sequencing in combination with molecular biology techniques. The association between the somatic mutations and downstream activation of the PI3K-mTOR pathway suggests that HME is a neurodevelopmental disease caused by gain-of-function activation of the PI3K-AKT-mTOR pathway., Summary: The studies reviewed suggest that somatic mutations of the PI3K-AKT-mTOR pathway limited to the brain may represent one cause of HME. Dysregulation of this pathway has possible therapeutic potential in the identification of HME. Somatic mutations may be an important yet underappreciated disease mechanism in developmental neurological diseases.
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- 2013
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18. Time to pediatric epilepsy surgery is related to disease severity and nonclinical factors.
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Baca CB, Vickrey BG, Vassar S, Hauptman JS, Dadour A, Oh T, Salamon N, Vinters HV, Sankar R, and Mathern GW
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- Adolescent, Child, Child, Preschool, Epilepsy diagnosis, Ethnicity, Female, Humans, Incidence, Insurance, Health statistics & numerical data, Magnetic Resonance Imaging methods, Male, Neurosurgical Procedures, Referral and Consultation, Risk Factors, Time Factors, Treatment Outcome, Epilepsy epidemiology, Epilepsy surgery
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Objective: To identify clinical and nonclinical factors associated with time from epilepsy onset to surgical evaluation and treatment among a cohort of children having epilepsy surgery., Methods: Data were abstracted from records of 430 children (younger than 18 years) who had epilepsy neurosurgery at the University of California, Los Angeles from 1986 to 2010. Multivariable Cox proportional hazards models were used to analyze unique associations of clinical severity, pre-referral brain MRI, and sociodemographic characteristics with time to surgery., Results: Shorter time to surgery was associated with active (hazard ratio [HR] 5.67, 95% confidence interval [CI] 3.74-8.70) and successfully treated infantile spasms (HR 2.20, 95% CI 1.63-2.96); daily or more seizures (HR 2.09, 95% CI 1.58-2.76); MRI before referral regardless of imaging findings (HR 1.95, 95% CI 1.47-2.58); private insurance (HR 1.54, 95% CI 1.14-2.09); and Hispanic ethnicity (HR 1.38, 95% CI 1.01-1.87). There were race/ethnicity by insurance interactions (log-rank p = 0.049) with shortest time to surgery for Hispanic children with private insurance., Conclusions: Shorter intervals to surgical treatment were associated with greater epilepsy severity and insurance type, consistent with existing literature. However, associations of shorter times to treatment with having a brain MRI before referral and Hispanic ethnicity were unexpected and warrant further investigation. More knowledgeable referring providers and parents with greater help-seeking capability may explain obtaining an MRI before referral. Shorter intervals to surgery among Hispanic children may relate to the same factors yielding an increased volume of Hispanic children receiving surgery at the University of California, Los Angeles since 2000.
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- 2013
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19. FDG-PET/MRI coregistration improves detection of cortical dysplasia in patients with epilepsy.
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Salamon N, Kung J, Shaw SJ, Koo J, Koh S, Wu JY, Lerner JT, Sankar R, Shields WD, Engel J Jr, Fried I, Miyata H, Yong WH, Vinters HV, and Mathern GW
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- Adolescent, Adult, Brain Mapping, Child, Child, Preschool, Cohort Studies, Electroencephalography methods, Epilepsy complications, Epilepsy pathology, Female, Humans, Image Processing, Computer-Assisted, Infant, Male, Middle Aged, Retrospective Studies, Young Adult, Epilepsy diagnostic imaging, Fluorodeoxyglucose F18, Magnetic Resonance Imaging, Malformations of Cortical Development complications, Malformations of Cortical Development diagnostic imaging, Malformations of Cortical Development pathology, Positron-Emission Tomography
- Abstract
Objective: Patients with cortical dysplasia (CD) are difficult to treat because the MRI abnormality may be undetectable. This study determined whether fluorodeoxyglucose (FDG)-PET/MRI coregistration enhanced the recognition of CD in epilepsy surgery patients., Methods: Patients from 2004-2007 in whom FDG-PET/MRI coregistration was a component of the presurgical evaluation were compared with patients from 2000-2003 without this technique. For the 2004-2007 cohort, neuroimaging and clinical variables were compared between patients with mild Palmini type I and severe Palmini type II CD., Results: Compared with the 2000-2003 cohort, from 2004-2007 more CD patients were detected, most had type I CD, and fewer cases required intracranial electrodes. From 2004-2007, 85% of type I CD cases had normal non-University of California, Los Angeles (UCLA) MRI scans. UCLA MRI identified CD in 78% of patients, and 37% of type I CD cases had normal UCLA scans. EEG and neuroimaging findings were concordant in 52% of type I CD patients, compared with 89% of type II CD patients. FDG-PET scans were positive in 71% of CD cases, and type I CD patients had less hypometabolism compared with type II CD patients. Postoperative seizure freedom occurred in 82% of patients, without differences between type I and type II CD cases., Conclusions: Incorporating fluorodeoxyglucose-PET/MRI coregistration into the multimodality presurgical evaluation enhanced the noninvasive identification and successful surgical treatment of patients with cortical dysplasia (CD), especially for the 33% of patients with nonconcordant findings and those with normal MRI scans from mild type I CD.
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- 2008
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20. Infantile spasm-associated microencephaly in tuberous sclerosis complex and cortical dysplasia.
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Chandra PS, Salamon N, Nguyen ST, Chang JW, Huynh MN, Cepeda C, Leite JP, Neder L, Koh S, Vinters HV, and Mathern GW
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- Child, Cohort Studies, Female, Humans, Infant, Newborn, Male, Microcephaly complications, Cerebral Cortex abnormalities, Cerebral Cortex pathology, Microcephaly pathology, Spasms, Infantile complications, Spasms, Infantile pathology, Tuberous Sclerosis complications, Tuberous Sclerosis pathology
- Abstract
Objective: In children with and without infantile spasms, this study determined brain volumes and cell densities in epilepsy surgery patients with tuberous sclerosis complex (TSC) and cortical dysplasia with balloon cells (CD)., Methods: We compared TSC (n = 18) and CD (n = 17) patients with normal/autopsy controls (n = 20) for MRI gray and white matter volumes and neuronal nuclei (NeuN) cell densities., Results: In patients without a history of infantile spasms, TSC cases showed decreased gray and white matter volumes (-16%). In cases with a history of infantile spasms, both CD (-25%) and TSC (-35%) patients showed microencephaly. This was confirmed in monozygotic twins with TSC, where the twin with a history of spasms had cerebral volumes less (-16%) than the twin without a history of seizures. Regardless of seizure history, TSC patients showed decreased NeuN cell densities in lower gray matter (-36%), whereas CD patients had increased densities in upper cortical (+52%) and white matter regions (+65%). For TSC patients, decreased lower gray matter NeuN densities correlated with reduced MRI volumes., Conclusions: Patients with tuberous sclerosis without spasms showed microencephaly associated with decreased cortical neuronal densities. In contrast, cortical dysplasia patients without spasms were normocephalic with increased cell densities. This supports the concept that tuberous sclerosis and cortical dysplasia have different pathogenetic mechanisms despite similarities in refractory epilepsy and postnatal histopathology. Furthermore, a history of infantile spasms was associated with reduced cerebral volumes in both cortical dysplasia and tuberous sclerosis patients, suggesting that spasms or their treatment may contribute to microencephaly independent of etiology.
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- 2007
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21. Surgery for symptomatic infant-onset epileptic encephalopathy with and without infantile spasms.
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Jonas R, Asarnow RF, LoPresti C, Yudovin S, Koh S, Wu JY, Sankar R, Shields WD, Vinters HV, and Mathern GW
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- Cohort Studies, Developmental Disabilities etiology, Drug Resistance, Early Diagnosis, Electroencephalography, Epilepsies, Partial drug therapy, Female, Humans, Infant, Intraoperative Complications mortality, Male, Postoperative Complications epidemiology, Postoperative Period, Preoperative Care, Psychological Tests, Retrospective Studies, Severity of Illness Index, Spasms, Infantile drug therapy, Telemetry, Treatment Outcome, Video Recording, Epilepsies, Partial surgery, Spasms, Infantile surgery
- Abstract
Children undergoing surgery with infant-onset epilepsy were classified into those with medically refractory infantile spasms (IS), successfully treated IS, and no IS history, and the groups were compared for pre- and postsurgery clinical and Vineland Adaptive Behavior Scale (VABS) developmental quotients (DQ). Children without an IS history were older at surgery and had longer epilepsy durations than those with IS despite similar substrates, surgeries, and seizure frequencies. In all groups, better postsurgery VABS-DQ scores were associated with early surgical intervention indicating that infant-onset epilepsy patients with or without IS are at risk for seizure-induced encephalopathy.
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- 2005
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22. Cerebral hemispherectomy: hospital course, seizure, developmental, language, and motor outcomes.
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Jonas R, Nguyen S, Hu B, Asarnow RF, LoPresti C, Curtiss S, de Bode S, Yudovin S, Shields WD, Vinters HV, and Mathern GW
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- Anticonvulsants therapeutic use, Blood Loss, Surgical, Blood Transfusion, Brain abnormalities, Brain Damage, Chronic epidemiology, Brain Ischemia complications, Brain Ischemia surgery, Cerebral Cortex abnormalities, Cerebral Infarction complications, Cerebral Infarction surgery, Child, Preschool, Cohort Studies, Combined Modality Therapy, Developmental Disabilities etiology, Encephalitis complications, Encephalitis surgery, Epilepsies, Partial drug therapy, Epilepsies, Partial etiology, Epilepsies, Partial surgery, Epilepsy drug therapy, Epilepsy etiology, Female, Hemispherectomy adverse effects, Hemispherectomy mortality, Humans, Infant, Language Development Disorders etiology, Magnetic Resonance Imaging, Male, Movement Disorders etiology, Plasma Substitutes therapeutic use, Postoperative Complications epidemiology, Postoperative Complications etiology, Preoperative Care, Retrospective Studies, Severity of Illness Index, Treatment Outcome, Developmental Disabilities surgery, Epilepsy surgery, Hemispherectomy statistics & numerical data, Language Development Disorders surgery, Movement Disorders surgery
- Abstract
Objective: To compare hemispherectomy patients with different pathologic substrates for hospital course, seizure, developmental, language, and motor outcomes., Methods: The authors compared hemispherectomy patients (n = 115) with hemimegalencephaly (HME; n = 16), hemispheric cortical dysplasia (hemi CD; n = 39), Rasmussen encephalitis (RE; n = 21), infarct/ischemia (n = 27), and other/miscellaneous (n = 12) for differences in operative management, postsurgery seizure control, and antiepilepsy drug (AED) usage. In addition, Vineland Adaptive Behavior Scale (VABS) developmental quotients (DQ), language, and motor assessments were performed pre- or postsurgery, or both., Results: Surgically, HME patients had the greatest perioperative blood loss, and the longest surgery time. Fewer HME patients were seizure free or not taking AEDs 1 to 5 years postsurgery, but the differences between pathologic groups were not significant. Postsurgery, 66% of HME patients had little or no language and worse motor scores in the paretic limbs. By contrast, 40 to 50% of hemi CD children showed near normal language and motor assessments, similar to RE and infarct/ischemia cases. VABS DQ scores showed +5 points or more improvement postsurgery in 57% of patients, and hemi CD (+12.7) and HME (+9.1) children showed the most progress compared with RE (+4.6) and infarct/ischemia (-0.6) cases. Postsurgery VABS DQ scores correlated with seizure duration, seizure control, and presurgery DQ scores., Conclusions: The pathologic substrate predicted pre- and postsurgery differences in outcomes, with hemimegalencephaly (but not hemispheric cortical dysplasia) patients doing worse in several domains. Furthermore, shorter seizure durations, seizure control, and greater presurgery developmental quotients predicted better postsurgery developmental quotients in all patients, irrespective of pathology.
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- 2004
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23. Hippocampal GABA and glutamate transporter immunoreactivity in patients with temporal lobe epilepsy.
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Mathern GW, Mendoza D, Lozada A, Pretorius JK, Dehnes Y, Danbolt NC, Nelson N, Leite JP, Chimelli L, Born DE, Sakamoto AC, Assirati JA, Fried I, Peacock WJ, Ojemann GA, and Adelson PD
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- Adolescent, Adult, Aged, Amino Acid Transport System X-AG, Child, Female, Humans, Immunohistochemistry, Male, Middle Aged, Prospective Studies, ATP-Binding Cassette Transporters analysis, Epilepsy, Temporal Lobe pathology, Hippocampus pathology, gamma-Aminobutyric Acid analysis
- Abstract
Objective: Sodium-coupled transporters remove extracellular neurotransmitters and alterations in their function could enhance or suppress synaptic transmission and seizures. This study determined hippocampal gamma-aminobutyric acid (GABA) and glutamate transporter immunoreactivity (IR) in temporal lobe epilepsy (TLE) patients., Methods: Hippocampal sclerosis (HS) patients (n = 25) and non-HS cases (mass lesion and cryptogenic; n = 20) were compared with nonseizure autopsies (n = 8). Hippocampal sections were studied for neuron densities along with IR for glutamate decarboxylase (GAD; presynaptic GABA terminals), GABA transporter-1 (GAT-1; presynaptic GABA transporter), GAT-3 (astrocytic GABA transporter), excitatory amino acid transporter 3 (EAAT3; postsynaptic glutamate transporter), and EAAT2-1 (glial glutamate transporters)., Results: Compared with autopsies, non-HS cases with similar neuron counts showed: 1) increased GAD IR gray values (GV) in the fascia dentata outer molecular layer (OML), hilus, and stratum radiatum; 2) increased GAT-1 OML GVs; 3) increased astrocytic GAT-3 GVs in the hilus and Ammon's horn; and 4) no IR differences for EAAT3-1. HS patients with decreased neuron densities demonstrated: 1) increased OML and inner molecular layer GAD puncta; 2) decreased GAT-1 puncta relative to GAD in the stratum granulosum and pyramidale; 3) increased GAT-1 OML GVs; 4) decreased GAT-3 GVs; 5) increased EAAT3 IR on remaining granule cells and pyramids; 6) decreased glial EAAT2 GVs in the hilus and CA1 stratum radiatum associated with neuron loss; and 7) increased glial EAAT1 GVs in CA2/3 stratum radiatum., Conclusions: Hippocampal GABA and glutamate transporter IR differ in TLE patients compared with autopsies. These data support the hypothesis that excitatory and inhibitory neurotransmission and seizure susceptibility could be altered by neuronal and glial transporters in TLE patients.
- Published
- 1999
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24. Aberrant hippocampal mossy fiber sprouting correlates with greater NMDAR2 receptor staining.
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Mathern GW, Leite JP, Babb TL, Pretorius JK, Kuhlman PA, Mendoza D, Fried I, Sakamoto AC, Assirati JA, Adelson PD, and Peacock WJ
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- Adult, Aged, Analysis of Variance, Animals, Functional Laterality physiology, Hippocampus drug effects, Humans, Immunohistochemistry, Male, Middle Aged, Nerve Fibers drug effects, Neurons drug effects, Neurons ultrastructure, Rats, Rats, Sprague-Dawley, Sclerosis, Staining and Labeling, Synapses physiology, Epilepsy, Temporal Lobe pathology, Excitatory Amino Acid Agonists pharmacology, Hippocampus ultrastructure, Kainic Acid pharmacology, Nerve Fibers ultrastructure, Receptors, N-Methyl-D-Aspartate analysis
- Abstract
This study determined in temporal lobe epilepsy patients and rats injected with intrahippocampal kainate (KA) whether fascia dentata molecular layer mossy fiber sprouting was associated with increases in NMDAR2 immunoreactivity (IR). Patients with hippocampal sclerosis (n = 11) were compared with those with temporal mass lesions (n = 7) and material obtained at autopsies (n = 4); and unilateral KA-injected rat hippocampi (n = 7) were compared with the contralateral saline-injected side and non-lesioned animals (n = 7; control). Hippocampi were studied for neo-Timm's stained mossy fiber sprouting and NMDAR2 IR. The staining was quantified as gray values (GV) using computer image analysis. Hippocampal sclerosis patients and KA-injected rats showed the greatest inner molecular layer (IML) mossy fiber sprouting and NMDAR2 staining. Compared with autopsies and patients with mass lesions, hippocampal sclerosis patients had greater IML neo-Timm's (p = 0.0018) and NMDAR2 staining (p = 0.0063). Similarly, compared with controls and saline-injected rats, KA-injected hippocampi showed greater IML mossy fiber sprouting and NMDAR2 IR (p = 0.0001). Furthermore, IML mossy fiber sprouting positively correlated with greater IML NMDAR2 staining in both human and experimental rat groups (p < 0.0099). These results support the hypothesis that in severely damaged hippocampi abnormal mossy fiber sprouting and concordant increases in IML NMDAR2 receptor staining may contribute or partially explain granule cell hyperexcitability and the pathophysiology of hippocampal epilepsy.
- Published
- 1996
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