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Thompson, Eric Michael

Overview:

My translational and clinical research focus is pediatric brain tumors. My translational research involves 1) using transgenic models of diffuse intrinsic pontine glioma to characterize the mechanism of therapeutics administered via convection enhanced delivery and 2) to characterize the mechanism of immunogenicity of oncolytic viral immunotherapy in immunocompetent models of solid tumor and disseminated medulloblastoma.

My clinical research focuses on 1) using a novel peptide vaccine to target CMV antigens to treat children with recurrent medulloblastoma and malignant glioma and 2) using oncolytic poliovirus to treat children with recurrent malignant glioma.

Positions:

Assistant Professor of Neurosurgery

Neurosurgery
School of Medicine

Assistant Professor in Pediatrics

Pediatrics
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 2002

B.S. — Duke University

M.D. 2006

M.D. — University of Nebraska College of Medicine

Neurological Surgery Resident, Neurosurgery

Oregon Health and Science University

Pediatric Neurological Surgery Fellow, Neurosurgery

The Hospital For Sick Children

News:

Total Anomalous Pulmonary Venous Drainage

November 24, 2015 — Clinical Practice Today

Grants:

Phase Ib study of Oncolytic Polio/Rhinovirus Recombinant Against Recurrent Malignant Glioma in Children

Administered By
Duke Cancer Institute
AwardedBy
Istari Oncology
Role
Principal Investigator
Start Date
September 20, 2017
End Date
July 24, 2021

Phase I study of Oncolytic Polio/Rhinovirus Recombinant Against Recurrent Malignant Glioma in Children

Administered By
Neurosurgery
AwardedBy
Musella Foundation For Brain Tumor Research & Information, Inc
Role
Principal Investigator
Start Date
August 01, 2016
End Date
July 31, 2018

Phase-1 clinical trial of PVSRIPO oncolytic immunotherapy in pediatric HGG

Administered By
Neurosurgery
AwardedBy
Solving Kids' Cancer
Role
Co Investigator
Start Date
April 01, 2016
End Date
March 31, 2018

Optimizing the Convection Enhanced Delivery of Targeted Agents for Midline Gliomas

Administered By
Neurosurgery
AwardedBy
Southeastern Brain Tumor Foundation
Role
Principal Investigator
Start Date
July 01, 2016
End Date
December 31, 2017
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Publications:

The role of angiogenesis in Group 3 medulloblastoma pathogenesis and survival.

Of the 4 medulloblastoma subgroups, Group 3 is the most aggressive but the importance of angiogenesis is unknown. This study sought to determine the role of angiogenesis and identify clinically relevant biomarkers of tumor vascularity and survival in Group 3 medulloblastoma.VEGFA mRNA expression and survival from several patient cohorts were analyzed. Group 3 xenografts were implanted intracranially in nude rats. Dynamic susceptibility weighted (DSC) MRI and susceptibility weighted imaging (SWI) were obtained. DSC MRI was used to calculate relative cerebral blood volume (rCBV) and flow (rCBF). Tumor vessel density and rat vascular endothelial growth factor alpha (VEGFA) expression were determined.Patient VEGFA mRNA levels were significantly elevated in Group 3 compared with the other subgroups (P < 0.001) and associated with survival. Xenografts D283, D341, and D425 were identified as Group 3 by RNA hierarchical clustering and MYC amplification. The D283 group had the lowest rCBV and rCBF, followed by D341 and D425 (P < 0.05). These values corresponded to histological vessel density (P < 0.05), rat VEGFA expression (P < 0.05), and survival (P = 0.002). Gene set enrichment analysis identified 5 putative genes with expression profiles corresponding with these findings: RNH1, SCG2, VEGFA, AGGF1, and PROK2. SWI identified 3 xenograft-independent categories of intratumoral vascular architecture with distinct survival (P = 0.004): organized, diffuse microvascular, and heterogeneous.Angiogenesis plays an important role in Group 3 medulloblastoma pathogenesis and survival. DSC MRI and SWI are clinically relevant biomarkers for tumor vascularity and overall survival and can be used to direct the use of antivascular therapies for patients with Group 3 medulloblastoma.

Authors
Thompson, EM; Keir, ST; Venkatraman, T; Lascola, C; Yeom, KW; Nixon, AB; Liu, Y; Picard, D; Remke, M; Bigner, DD; Ramaswamy, V; Taylor, MD
MLA Citation
Thompson, EM, Keir, ST, Venkatraman, T, Lascola, C, Yeom, KW, Nixon, AB, Liu, Y, Picard, D, Remke, M, Bigner, DD, Ramaswamy, V, and Taylor, MD. "The role of angiogenesis in Group 3 medulloblastoma pathogenesis and survival." Neuro-oncology 19.9 (September 2017): 1217-1227.
PMID
28379574
Source
epmc
Published In
Neuro-Oncology
Volume
19
Issue
9
Publish Date
2017
Start Page
1217
End Page
1227
DOI
10.1093/neuonc/nox033

The clinical and financial impact of a pediatric surgical neuro-oncology clinical trial.

Pediatric surgical trials are rare and the impact of such trials on the institutions in which they are conducted is unknown. The purpose of this study was to analyze the clinical and financial impact of The Re-MATCH trial, a Phase I clinical trial requiring the biopsy or resection of recurrent medulloblastoma or PNET for enrollment. Inpatient financial and clinical volume information was collected during the 3 years of trial enrollment and the years preceding and following it. The primary endpoints were the difference in direct contribution margin (DCM), or net gain, of study and non-study patients and the difference in surgical volume during the study and non-study periods. The trial enrolled 18 patients; 15 had surgery at the sponsor institution and three had surgery at their home institution, then transferred tumor material to the sponsor institution. There were no differences between the two groups for potentially confounding variables such as neurosurgical procedure work relative value units (P = 0.13) or insurance provider (P = 0.26). There was no difference between the inpatient DCM per case for the institution for non-study patients (mean ± SD, $9039 ± $28,549) and study patients ($14,332 ± $20,231) (P = 0.4819). During the non-study period, there were a mean of 2.78 ± 1.65 pediatric brain tumor resections per month compared to 3.34 ± 1.66 cases per month during the study period, a 17% increase. When the 15 study patients were excluded, there were 2.97 ± 1.64 cases per month, a 7% increase. However, this increase in total case volume including study and non-study patients was not significant (P = 0.121). Phase I investigator-initiated surgically-based clinical trials may increase institutional surgical volume without imposing a financial burden. Finances are unlikely to be a barrier for researchers negotiating for resources to conduct such trials.

Authors
Thompson, EM; Gururangan, S; Grant, G; Mitchell, D; Sampson, JH
MLA Citation
Thompson, EM, Gururangan, S, Grant, G, Mitchell, D, and Sampson, JH. "The clinical and financial impact of a pediatric surgical neuro-oncology clinical trial." Journal of neuro-oncology 132.1 (March 2017): 83-87.
PMID
27864705
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
132
Issue
1
Publish Date
2017
Start Page
83
End Page
87
DOI
10.1007/s11060-016-2338-z

Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis.

Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner.We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (<1·5 cm(2) tumour remaining), or sub-total resection (≥1·5 cm(2) tumour remaining). We did multivariable analyses of overall survival and progression-free survival using the variables molecular subgroup (WNT, SHH, group 4, and group 3), age (<3 vs ≥3 years old), metastatic status (metastases vs no metastases), geographical location of therapy (North America/Australia vs rest of the world), receipt of chemotherapy (yes vs no) and receipt of craniospinal irradiation (<30 Gy or >30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival.We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox models of progression-free and overall survival. We found that the prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. We identified a progression-free survival benefit for gross total resection over sub-total resection (hazard ratio [HR] 1·45, 95% CI 1·07-1·96, p=0·16) but no overall survival benefit (HR 1·23, 0·87-1·72, p=0·24). We saw no progression-free survival or overall survival benefit for gross total resection compared with near-total resection (HR 1·05, 0·71-1·53, p=0·8158 for progression-free survival and HR 1·14, 0·75-1·72, p=0·55 for overall survival). No significant survival benefit existed for greater extent of resection for patients with WNT, SHH, or group 3 tumours (HR 1·03, 0·67-1·58, p=0·89 for sub-total resection vs gross total resection). For patients with group 4 tumours, gross total resection conferred a benefit to progression-free survival compared with sub-total resection (HR 1·97, 1·22-3·17, p=0·0056), especially for those with metastatic disease (HR 2·22, 1·00-4·93, p=0·050). However, gross total resection had no effect on overall survival compared with sub-total resection in patients with group 4 tumours (HR 1·67, 0·93-2·99, p=0·084).The prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. Although maximum safe surgical resection should remain the standard of care, surgical removal of small residual portions of medulloblastoma is not recommended when the likelihood of neurological morbidity is high because there is no definitive benefit to gross total resection compared with near-total resection.Canadian Cancer Society Research Institute, Terry Fox Research Institute, Canadian Institutes of Health Research, National Institutes of Health, Pediatric Brain Tumor Foundation, and the Garron Family Chair in Childhood Cancer Research.

Authors
Thompson, EM; Hielscher, T; Bouffet, E; Remke, M; Luu, B; Gururangan, S; McLendon, RE; Bigner, DD; Lipp, ES; Perreault, S; Cho, Y-J; Grant, G; Kim, S-K; Lee, JY; Rao, AAN; Giannini, C; Li, KKW; Ng, H-K; Yao, Y; Kumabe, T; Tominaga, T; Grajkowska, WA; Perek-Polnik, M; Low, DCY; Seow, WT; Chang, KTE; Mora, J; Pollack, IF; Hamilton, RL; Leary, S; Moore, AS; Ingram, WJ; Hallahan, AR; Jouvet, A; Fèvre-Montange, M; Vasiljevic, A; Faure-Conter, C; Shofuda, T; Kagawa, N; Hashimoto, N; Jabado, N et al.
MLA Citation
Thompson, EM, Hielscher, T, Bouffet, E, Remke, M, Luu, B, Gururangan, S, McLendon, RE, Bigner, DD, Lipp, ES, Perreault, S, Cho, Y-J, Grant, G, Kim, S-K, Lee, JY, Rao, AAN, Giannini, C, Li, KKW, Ng, H-K, Yao, Y, Kumabe, T, Tominaga, T, Grajkowska, WA, Perek-Polnik, M, Low, DCY, Seow, WT, Chang, KTE, Mora, J, Pollack, IF, Hamilton, RL, Leary, S, Moore, AS, Ingram, WJ, Hallahan, AR, Jouvet, A, Fèvre-Montange, M, Vasiljevic, A, Faure-Conter, C, Shofuda, T, Kagawa, N, Hashimoto, N, and Jabado, N et al. "Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis." The Lancet. Oncology 17.4 (April 2016): 484-495.
PMID
26976201
Source
epmc
Published In
The Lancet Oncology
Volume
17
Issue
4
Publish Date
2016
Start Page
484
End Page
495
DOI
10.1016/s1470-2045(15)00581-1

Utility of diffusion tensor imaging studies linked to neuronavigation and other modalities in repeat hemispherotomy for intractable epilepsy.

OBJECT Hemispherectomy for unilateral, medically refractory epilepsy is associated with excellent long-term seizure control. However, for patients with recurrent seizures following disconnection, workup and investigation can be challenging, and surgical options may be limited. Few studies have examined the role of repeat hemispherotomy in these patients. The authors hypothesized that residual fiber connections between the hemispheres could be the underlying cause of recurrent epilepsy in these patients. Diffusion tensor imaging (DTI) was used to test this hypothesis, and to target residual connections at reoperation using neuronavigation. METHODS The authors identified 8 patients with recurrent seizures following hemispherectomy who underwent surgery between 1995 and 2012. Prolonged video electroencephalography recordings documented persistent seizures arising from the affected hemisphere. In all patients, DTI demonstrated residual white matter association fibers connecting the hemispheres. A repeat craniotomy and neuronavigation-guided targeted disconnection of these residual fibers was performed. Engel class was used to determine outcome after surgery at a minimum of 2 years of follow-up. RESULTS Two patients underwent initial hemidecortication and 6 had periinsular hemispherotomy as their first procedures at a median age of 9.7 months. Initial pathologies included hemimegalencephaly (n = 4), multilobar cortical dysplasia (n = 3), and Rasmussen's encephalitis (n = 1). The mean duration of seizure freedom for the group after the initial procedure was 32.5 months (range 6-77 months). In all patients, DTI showed limited but definite residual connections between the 2 hemispheres, primarily across the rostrum/genu of the corpus callosum. The median age at reoperation was 6.8 years (range 1.3-14 years). The average time taken for reoperation was 3 hours (range 1.8-4.3 hours), with a mean blood loss of 150 ml (range 50-250 ml). One patient required a blood transfusion. Five patients are seizure free, and the remaining 3 patients are Engel Class II, with a minimum follow-up of 24 months for the group. CONCLUSIONS Repeat hemispherotomy is an option for consideration in patients with recurrent intractable epilepsy following failed surgery for catastrophic epilepsy. In conjunction with other modalities to establish seizure onset zones, advanced MRI and DTI sequences may be of value in identifying patients with residual connectivity between the affected and unaffected hemispheres. Targeted disconnection of these residual areas of connectivity using neuronavigation may result in improved seizure outcomes, with minimal and acceptable morbidity.

Authors
Kiehna, EN; Widjaja, E; Holowka, S; Carter Snead, O; Drake, J; Weiss, SK; Ochi, A; Thompson, EM; Go, C; Otsubo, H; Donner, EJ; Rutka, JT
MLA Citation
Kiehna, EN, Widjaja, E, Holowka, S, Carter Snead, O, Drake, J, Weiss, SK, Ochi, A, Thompson, EM, Go, C, Otsubo, H, Donner, EJ, and Rutka, JT. "Utility of diffusion tensor imaging studies linked to neuronavigation and other modalities in repeat hemispherotomy for intractable epilepsy." Journal of neurosurgery. Pediatrics 17.4 (April 2016): 483-490.
PMID
26651159
Source
epmc
Published In
Journal of neurosurgery. Pediatrics
Volume
17
Issue
4
Publish Date
2016
Start Page
483
End Page
490
DOI
10.3171/2015.7.peds15101

Use of lumbar laminoplasty vs. laminotomy for transection of the filum terminale does not affect early complication rates or postoperative course.

Various techniques are used for spinal cord untethering. The purpose of this study was to compare patient characteristics, postoperative course, and early complications after laminotomy vs. laminoplasty for transection of the filum terminale for tethered cord release.Retrospective analysis of clinical and magnetic resonance imaging data was undertaken for all patients (<18 years) who underwent tethered cord release by transection of the filum terminale at Oregon Health & Science University, Doernbecher Children's Hospital, from 2000 to 2011.Data from two hundred and forty-eight patients were analyzed. Mean age was 5.2 years (range 0.3 to 16.8 years). Access to the thecal space during surgery was achieved using laminotomy or laminoplasty in 82 (33.1 %) and 166 (66.9 %) patients, respectively. Laminoplasty patients were significantly younger than laminotomy patients (3.2 vs. 9.3 years, p<0.0001); other clinical and radiographic characteristics were similar between the groups. Nine patients (3.6 %) experienced early complications, including cerebrospinal fluid leak (n=2), suprafascial infection requiring surgical management and intravenous (IV) antibiotics (n=3) or IV antibiotics alone (n=1), a small area of peri-incisional cutaneous necrosis (n=1), perioperative seizures (n=1), and mild, transient malignant hyperthermia (n=1). There was no difference in the number of early complications between the two groups. Univariate and multivariate analyses revealed no significant risk factor for postoperative complication associated with technique. As judged by caregivers, independent of surgical technique, 97 % of patients improved after surgery.There was no difference in complication risk when performing transection of the filum terminale for tethered cord release using laminotomy or laminoplasty.

Authors
Strong, MJ; Thompson, EM; Roundy, N; Selden, NR
MLA Citation
Strong, MJ, Thompson, EM, Roundy, N, and Selden, NR. "Use of lumbar laminoplasty vs. laminotomy for transection of the filum terminale does not affect early complication rates or postoperative course." Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 31.4 (April 2015): 597-601.
PMID
25578961
Source
epmc
Published In
Child's Nervous System
Volume
31
Issue
4
Publish Date
2015
Start Page
597
End Page
601
DOI
10.1007/s00381-015-2615-8

Using a 2-variable method in radionuclide shuntography to predict shunt patency.

OBJECT: Radionuclide shuntography interpretation is uncertain when the tracer fails to enter the ventricles but quickly drains distally or when the tracer enters the ventricles but takes longer than 15 minutes to drain distally. The purpose of this study was to aid in the clinical interpretation of a variety of shuntography results and to determine the applicability of shuntography in different patient populations. METHODS: The results of 259 shuntograms were reviewed. Chi-square analysis was performed to evaluate the relationship between clinical variables and shuntography results. Two-by-two binary classification analyses were performed to determine the sensitivity, specificity, positive predictive value, and negative predictive value for 4 different combinatorial types of shuntography results based on 2 variables: ventricular tracer entry and distal tracer drainage. RESULTS: Median patient age was 19 years, and 51% of patients were male. The most common presentation in patients undergoing shuntography was headache (169/254, 66.5%) with radiographically stable ventricle size. Of 227 patients with available imaging data, 163 (71.8%) presented with the same ventricle size as shown on a previous asymptomatic scan, 43 (18.9%) had larger ventricles, and 21 (9.2%) had smaller ventricles. Within 30 days of shuntography, 74 of 259 patients (28.6%) underwent surgical shunt exploration: 65 were found to have an obstructed shunt and 9 were found to have a patent shunt. Of those patients not undergoing surgery, the median length of benign clinical follow-up was 1051 days. Clinical variables were not significantly associated with shuntography results, including valve type (p = 0.180), ventricle size (p = 0.556), age (p = 0.549), distal drainage site (p = 0.098), and hydrocephalus etiology (p = 0.937). Shuntography results of patients with myelomeningocele were not dissociable from those of the group as a whole. Sensitivity to diagnose shunt failure was lowest (37.5%) but specificity was highest (97.2%) when the definition of a "normal" shuntogram included any tracer movement into the distal site within 45 minutes. Conversely, sensitivity was highest (87.5%) and specificity was lowest (51.4%) when the definition was limited exclusively to tracer entry into the ventricles and distal drainage within 15 minutes. CONCLUSIONS: Even with a stringent definition of a "normal" shuntogram, sensitivity and specificity were relatively low for a diagnostic test. Clinical variables such as valve type, ventricle size, patient age, distal drainage site, and etiology of hydrocephalus were not associated with shuntography results.

Authors
Thompson, EM; Wagner, K; Kronfeld, K; Selden, NR
MLA Citation
Thompson, EM, Wagner, K, Kronfeld, K, and Selden, NR. "Using a 2-variable method in radionuclide shuntography to predict shunt patency." Journal of neurosurgery 121.6 (December 2014): 1504-1507.
PMID
25259566
Source
epmc
Published In
Journal of neurosurgery
Volume
121
Issue
6
Publish Date
2014
Start Page
1504
End Page
1507
DOI
10.3171/2014.8.jns132898

Results of a North American survey of rapid-sequence MRI utilization to evaluate cerebral ventricles in children.

OBJECT: Growing concern about potential adverse effects of ionizing radiation exposure during imaging studies is particularly relevant to the pediatric population. To decrease radiation exposure, many institutions use rapid-sequence (or quick-brain) MRI to evaluate cerebral ventricle size. There are obstacles, however, to widespread implementation of this imaging modality. The purpose of this study was to define and quantify these obstacles to positively affect institutional and governmental policy. METHODS: A 9-question survey was emailed to pediatric neurosurgeons who were either members or candidate members of the American Society of Pediatric Neurosurgeons at every one of 101 institutions in the US and Canada having such a neurosurgeon on staff. Responses were compiled and descriptive statistics were performed. RESULTS: Fifty-six institutions completed the survey. Forty-four (79%) of the 56 institutions currently have a rapid-sequence MRI protocol to evaluate ventricle size, while 36 (64%) use it routinely. Of the 44 institutions with a rapid-sequence MRI protocol, 29 (66%) have had a rapid-sequence MRI protocol for less than 5 years while 39 (89%) have had a rapid-sequence MRI protocol for no more than 10 years. Thirty-six (88%) of 41 rapid-sequence MRI users responding to this question obtain a T2-weighted rapid-sequence MRI while 13 (32%) obtain a T1-weighted rapid-sequence MRI. Twenty-eight (64%) of 44 institutions never use sedation while an additional 12 (27%) rarely use sedation to obtain a rapid-sequence MRI (less than 5% of studies). Of the institutions with an established rapid-sequence MRI protocol, obstacles to routine use include lack of emergency access to MRI facilities in 18 (41%), lack of staffing of MRI facilities in 12 (27%), and the inability to reimburse a rapid-sequence MRI protocol in 6 (14%). In the 12 institutions without rapid-sequence MRI, obstacles to implementation include lack of emergency access to MRI facilities in 8 (67%), lack of staffing of MRI facilities in 7 (58%), the inability to reimburse in 3 (25%), and lack of administrative support in 3 (25%). To evaluate pediatric head trauma, 53 (96%) of 55 institutions responding to this question use noncontrast CT, no institution uses rapid-sequence MRI, and only 2 (4%) use standard MRI. CONCLUSIONS: Many North American institutions have a rapid-sequence MRI protocol to evaluate ventricle size, with most developing this technique within the past 5 years. Most institutions never use sedation, and most obtain T2-weighted sequences. The greatest obstacles to the routine use of rapid-sequence MRI in institutions with and in those without a rapid-sequence MRI protocol are the lack of emergency access and staffing of the MRI facility during nights and weekends.

Authors
Thompson, EM; Baird, LC; Selden, NR
MLA Citation
Thompson, EM, Baird, LC, and Selden, NR. "Results of a North American survey of rapid-sequence MRI utilization to evaluate cerebral ventricles in children." Journal of neurosurgery. Pediatrics 13.6 (June 2014): 636-640.
PMID
24724716
Source
epmc
Published In
Journal of neurosurgery. Pediatrics
Volume
13
Issue
6
Publish Date
2014
Start Page
636
End Page
640
DOI
10.3171/2014.2.peds13567

Spontaneous improvement in urological dysfunction in children with congenital spinal lipomas of the conus medullaris.

Congenital spinal lipomas of the conus (SLCs) are among the most common closed neural tube defects. The treatment of SLC is an area of controversy because the true natural history of this condition is unknown. Here, the authors present two cases of SLC presenting in infancy with compromised lower urinary tract function, which was objectively confirmed by abnormal urodynamic studies. In both cases, there was spontaneous improvement in urodynamic parameters, with stable normal urinary function at the long-term follow-up. Although cases of spontaneous radiological regression of SLC have very infrequently been reported, they have not been associated with the reversal of already present neurological deficits. This report reinforces the need for further delineation of the true natural history of SLC and highlights the dynamic nature of associated neurological compromise over time.

Authors
Badhiwala, JH; Thompson, EM; Lorenzo, AJ; Kulkarni, AV
MLA Citation
Badhiwala, JH, Thompson, EM, Lorenzo, AJ, and Kulkarni, AV. "Spontaneous improvement in urological dysfunction in children with congenital spinal lipomas of the conus medullaris." Journal of neurosurgery. Pediatrics 13.5 (May 2014): 536-540.
PMID
24679080
Source
epmc
Published In
Journal of neurosurgery. Pediatrics
Volume
13
Issue
5
Publish Date
2014
Start Page
536
End Page
540
DOI
10.3171/2014.2.peds13519

Clinical significance of imaging and histological characteristics of filum terminale in tethered cord syndrome.

The pathophysiology of tethered cord syndrome (TCS) is uncertain; however, it has been suggested that fibrous and fatty elements within the filum terminale (FT) play a role. The objective of this study was to describe the radiological and histological features of the FT in TCS and determine if there are associations between those features and clinical outcomes, complications, and urodynamics.In this retrospective study, histological, MRI, and clinical data obtained in 293 patients with TCS who underwent FT transection were reviewed and analyzed in a multivariate analysis.The median patient age was 4.9 years (range 0.3-64.3 years). On MRI, a fatty filum was present in 65% of patients and a thickened filum (> 2 mm) was seen in 45%. Histologically, the FT contained prominent fibrous tissue in 95%, nerve twigs in 79%, adipose tissue in 59%, and vascular tissue in 36%. Histological features associated with a thickened filum on MR images were adipose tissue (OR 3.5, p < 0.001), nerve twigs (OR 2.2, p = 0.028), and vascular tissue (OR 0.5, p = 0.025). Adipose tissue was associated with a conus level below the L2-3 disc space (OR 2.3, p = 0.031) and with a fatty filum on imaging (OR 9.8, p < 0.001). Nerve twigs were associated with abnormal urodynamics (OR 10.9, p = 0.049). The only variable predictive of clinical improvement was conus level; patients with conus levels caudal to L-2 were less likely to improve postoperatively (OR 0.3, p = 0.042).Fibrous tissue was ubiquitous and may be important in the pathophysiology of TCS. Nerve twigs and adipose tissue were associated with abnormal urodynamics and low-lying coni, respectively. Although the majority of patients clinically improved, patients with normal conus levels had significantly better outcomes.

Authors
Thompson, EM; Strong, MJ; Warren, G; Woltjer, RL; Selden, NR
MLA Citation
Thompson, EM, Strong, MJ, Warren, G, Woltjer, RL, and Selden, NR. "Clinical significance of imaging and histological characteristics of filum terminale in tethered cord syndrome." Journal of neurosurgery. Pediatrics 13.3 (March 2014): 255-259.
PMID
24404969
Source
epmc
Published In
Journal of neurosurgery. Pediatrics
Volume
13
Issue
3
Publish Date
2014
Start Page
255
End Page
259
DOI
10.3171/2013.12.peds13370

Percutaneous trigeminal tractotomy-nucleotomy with use of intraoperative computed tomography and general anesthesia: report of 2 cases.

For confirming the correct location of the radiofrequency electrode before creation of a lesion, percutaneous CT-guided trigeminal tractotomy-nucleotomy is most commonly performed with the patient prone and awake. However, for patients whose facial pain and hypersensitivity are so severe that the patients are unable to rest their face on a support (as required with prone positioning), awake CT-guided tractotomy-nucleotomy might not be feasible. The authors describe 2 such patients, for whom percutaneous intraoperative CT-guided tractotomy-nucleotomy under general anesthesia was successful. One patient was a 79-year-old man with profound left facial postherpetic neuralgia, who was unable to tolerate awake CT-guided tractotomy-nucleotomy, and the other was a 45-year-old woman with intractable hemicranial pain that developed after a right frontal lesionectomy for epilepsy. Each patient underwent a percutaneous intraoperative CT-guided tractotomy-nucleotomy under general anesthesia. No complications occurred, and each patient reported excellent pain relief for up to 6 and 3 months after surgery, respectively. Percutaneous intraoperative CT-guided tractotomy-nucleotomy performed on anesthetized patients is effective for facial postherpetic neuralgia and postoperative hemicranial neuralgia.

Authors
Thompson, EM; Burchiel, KJ; Raslan, AM
MLA Citation
Thompson, EM, Burchiel, KJ, and Raslan, AM. "Percutaneous trigeminal tractotomy-nucleotomy with use of intraoperative computed tomography and general anesthesia: report of 2 cases." Neurosurgical focus 35.3 (September 2013): E5-. (Review)
PMID
23991818
Source
epmc
Published In
Neurosurgical focus
Volume
35
Issue
3
Publish Date
2013
Start Page
E5
DOI
10.3171/2013.6.focus13218

Inhibition of SUR1 decreases the vascular permeability of cerebral metastases.

Inhibition of sulfonylurea receptor 1 (SUR1) by glyburide has been shown to decrease edema after subarachnoid hemorrhage. We investigated if inhibiting SUR1 reduces cerebral edema due to metastases, the most common brain tumor, and explored the putative association of SUR1 and the endothelial tight junction protein, zona occludens-1 (ZO-1). Nude rats were intracerebrally implanted with small cell lung carcinoma (SCLC) LX1 or A2058 melanoma cells (n = 36). Rats were administered vehicle, glyburide (4.8 µg twice, orally), or dexamethasone (0.35 mg, intravenous). Blood-tumor barrier (BTB) permeability (K (trans)) was evaluated before and after treatment using dynamic contrast-enhanced magnetic resonance imaging. SUR1 and ZO-1 expression was evaluated using immunofluorescence and Western blots. In both models, SUR1 expression was significantly increased (P < .05) in tumors. In animals with SCLC, control mean K (trans) (percent change ± standard error) was 101.8 ± 36.6%, and both glyburide (-21.4 ± 14.2%, P < .01) and dexamethasone (-14.2 ± 13.1%, P < .01) decreased BTB permeability. In animals with melanoma, compared to controls (117.1 ± 43.4%), glyburide lowered BTB permeability increase (3.2 ± 15.4%, P < .05), while dexamethasone modestly lowered BTB permeability increase (63.1 ± 22.1%, P > .05). Both glyburide (P < .001) and dexamethasone (P < .01) decreased ZO-1 gap formation. By decreasing ZO-1 gaps, glyburide was at least as effective as dexamethasone at halting increased BTB permeability caused by SCLC and melanoma. Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema.

Authors
Thompson, EM; Pishko, GL; Muldoon, LL; Neuwelt, EA
MLA Citation
Thompson, EM, Pishko, GL, Muldoon, LL, and Neuwelt, EA. "Inhibition of SUR1 decreases the vascular permeability of cerebral metastases." Neoplasia (New York, N.Y.) 15.5 (May 2013): 535-543.
PMID
23633925
Source
epmc
Published In
Neoplasia (New York, N.Y.)
Volume
15
Issue
5
Publish Date
2013
Start Page
535
End Page
543
DOI
10.1593/neo.13164

Metastatic renal cell carcinoma to the third ventricle resembling a colloid cyst.

Authors
Wagner, KM; Thompson, EM; Ragel, BT
MLA Citation
Wagner, KM, Thompson, EM, and Ragel, BT. "Metastatic renal cell carcinoma to the third ventricle resembling a colloid cyst." Acta neurochirurgica 155.4 (April 2013): 737-739. (Letter)
PMID
23420117
Source
epmc
Published In
Acta Neurochirurgica
Volume
155
Issue
4
Publish Date
2013
Start Page
737
End Page
739
DOI
10.1007/s00701-013-1646-8

The effect of alpha-v integrin inhibition on the malignant characteristics of medulloblastoma.

Hypoxia induces an aggressive phenotype in some brain tumors in part due to hypoxia-inducible factor-1α (HIF-1α) and integrin expression. The importance of hypoxia in medulloblastoma is unclear and the interaction of HIF-1α and c-Myc in medulloblastoma has not been explored. The objective of this study was to determine if hypoxia induces an aggressive phenotype in human medulloblastoma cells that constitutively express high (D283 Med) or low (DAOY) levels of c-Myc and to determine if blocking α(v) integrins with the monoclonal antibody intetumumab inhibits hypoxia-induced cellular stress responses.Cells were grown at 21% and 1% O(2) and in the presence or absence of intetumumab. Measures of malignancy evaluated included cell proliferation, cell migration, and expression of vascular endothelial growth factor (VEGF), α(v) integrins, HIF-1α, and c-Myc.Both cell lines robustly expressed α(v) integrins. Hypoxic DAOY cells showed significantly increased proliferation compared with normoxic controls (p < 0.05), whereas D283 Med cells did not. Both cell lines exhibited a dose-dependent decrease in proliferation when treated with intetumumab (p < 0.05). Hypoxia did not increase DAOY migration, but intetumumab significantly inhibited migration at both oxygen conditions (p < 0.05). Intetumumab significantly decreased VEGF levels in DAOY cells at both oxygen conditions (p < 0.05) and in normoxic D283 cells (p < 0.01). Neither cell line demonstrated increased HIF-1α expression in response to hypoxia. However, hypoxic D283 Med cells grown in the presence of intetumumab demonstrated significantly decreased c-Myc expression (p < 0.05).Hypoxia did not clearly induce a more aggressive phenotype in medulloblastoma cells. Despite this result, intetumumab decreased medulloblastoma cell proliferation and migration and variably decreased VEGF and c-Myc expression in hypoxic conditions. Targeting α(v) integrins represents a promising potential adjuvant modality in the treatment of medulloblastoma, particularly subtypes that metastasize and overexpress VEGF and c-Myc.

Authors
Thompson, EM; Whitney, NL; Wu, YJ; Neuwelt, EA
MLA Citation
Thompson, EM, Whitney, NL, Wu, YJ, and Neuwelt, EA. "The effect of alpha-v integrin inhibition on the malignant characteristics of medulloblastoma." Journal of neurosurgery. Pediatrics 11.1 (January 2013): 60-67.
PMID
23082872
Source
epmc
Published In
Journal of neurosurgery. Pediatrics
Volume
11
Issue
1
Publish Date
2013
Start Page
60
End Page
67
DOI
10.3171/2012.9.peds12268

Optimal timing of autologous cranioplasty after decompressive craniectomy in children.

OBJECT: The object of this study was to determine if early cranioplasty after decompressive craniectomy for elevated intracranial pressure in children reduces complications. METHODS: Sixty-one consecutive cases involving pediatric patients who underwent autologous cranioplasty after decompressive craniectomy for raised intracranial pressure at a single academic children's hospital over 15 years were studied retrospectively. RESULTS: Sixty-one patients were divided into early (< 6 weeks; 28 patients) and late (≥ 6 weeks; 33 patients) cranioplasty cohorts. The cohorts were similar except for slightly lower age in the early (8.03 years) than the late (10.8 years) cranioplasty cohort (p < 0.05). Bone resorption after cranioplasty was significantly more common in the late (42%) than the early (14%) cranioplasty cohort (p < 0.05; OR 5.4). No other complication differed in incidence between the cohorts. CONCLUSIONS: After decompressive craniectomy for raised intracranial pressure in children, early (< 6 weeks) cranioplasty reduces the occurrence of reoperation for bone resorption, without altering the incidence of other complications.

Authors
Piedra, MP; Thompson, EM; Selden, NR; Ragel, BT; Guillaume, DJ
MLA Citation
Piedra, MP, Thompson, EM, Selden, NR, Ragel, BT, and Guillaume, DJ. "Optimal timing of autologous cranioplasty after decompressive craniectomy in children." Journal of neurosurgery. Pediatrics 10.4 (October 2012): 268-272.
PMID
22861195
Source
epmc
Published In
Journal of neurosurgery. Pediatrics
Volume
10
Issue
4
Publish Date
2012
Start Page
268
End Page
272
DOI
10.3171/2012.6.peds1268

The deleterious effects of methamphetamine use on initial presentation and clinical outcomes in aneurysmal subarachnoid hemorrhage.

OBJECT: The objective of this study was to retrospectively look at methamphetamine (MA) use in patients with aneurysmal subarachnoid hemorrhage (SAH) to determine if MA use affects clinical presentation and outcomes after aneurysmal SAH. METHODS: A retrospective review of patients admitted to the Oregon Health & Science University neurosurgical service with aneurysmal SAH during the past 6 years was undertaken. Variables analyzed included MA use, age, sex, cigarette use, Hunt and Hess grade, Fisher grade, admission blood pressure, aneurysm characteristics, occurrence of vasospasm, hospital length of stay (LOS), cerebral infarction, aneurysm treatment, and Glasgow Outcome Scale (GOS) score. Data differences between MA users and nonusers were statistically analyzed using multivariate logistic regression analysis. A separate comparison with randomly selected age-matched nonuser controls was also performed. RESULTS: Twenty-eight (7%) of 374 patients with aneurysmal SAH were identified as MA users. Methamphetamine users were younger than nonusers (45.2 vs 55.9 years, respectively; p <0.001). Despite a younger age, MA users had significantly higher Hunt and Hess grades than nonusers (3.0 vs 2.5, respectively; p <0.020) and age-matched controls (3.0 vs 2.0, respectively; p <0.001). Earliest available mean arterial pressure was significantly higher in MA users (122.1 vs 109.7, respectively; p = 0.005) than all nonusers but not age-matched controls. Methamphetamine users had significantly higher vasospasm rates than nonusers (92.9% vs 71.1%, respectively; p = 0.008) but similar rates as age-matched controls (92.9% vs 89.3%, respectively; p = 0.500). Glasgow Outcome Scale score did not differ significantly between users and nonusers (3 vs 4, respectively; p = 0.170), but users had significantly lower GOS scores than age-matched controls (3 vs 5, respectively; p <0.001). There was no statistically significant difference in the LOS between users and nonusers (18 days vs 16 days, respectively; p = 0.431) or users and age-matched controls (18 days vs 14 days, respectively; p = 0.250). In the multivariate analysis, MA use (OR 3.777, p = 0.018), age (p <0.001), Fisher grade (p = 0.011), Hunt and Hess grade (p <0.001), and cerebral infarction (p <0.001) were predictors of poor GOS score. The only predictor of vasospasm was age (p <0.001), although a strong predictive trend in MA use (p = 0.149) was found. Predictors of a hospital LOS >15 days included age (p = 0.002), Fisher grade (p = 0.002), Hunt and Hess grade (p <0.001), and cerebral infarction (p <0.001). Predictors of cerebral infarction include male sex (p = 0.022) and Hunt and Hess grade (p = 0.006), with vasospasm demonstrating a strong trend (p = 0.056). CONCLUSIONS: A history of MA use may predict poorer outcomes in patients who present with aneurysmal SAH. Methamphetamine users have significantly worse presentations and outcomes when compared with age-matched controls.

Authors
Beadell, NC; Thompson, EM; Delashaw, JB; Cetas, JS
MLA Citation
Beadell, NC, Thompson, EM, Delashaw, JB, and Cetas, JS. "The deleterious effects of methamphetamine use on initial presentation and clinical outcomes in aneurysmal subarachnoid hemorrhage." Journal of neurosurgery 117.4 (October 2012): 781-786.
PMID
22920957
Source
epmc
Published In
Journal of neurosurgery
Volume
117
Issue
4
Publish Date
2012
Start Page
781
End Page
786
DOI
10.3171/2012.7.jns12396

Vagus nerve stimulation for partial and generalized epilepsy from infancy to adolescence.

OBJECT: Vagus nerve stimulation (VNS) is approved by the FDA for the treatment of partial epilepsy in patients older than 12 years. Authors of the current study performed a large retrospective analysis and comparison of VNS outcomes in children with an age ≥ and < 12 years, including those with partial and generalized epilepsy. METHODS: A retrospective review of the records of pediatric patients (age < 18 years) who had undergone primary VNS system implantation between 2001 and 2010 by a single pediatric neurosurgeon was undertaken. Considered data included demographics, epilepsy type (partial vs generalized), seizure frequency, seizure duration, postictal period duration, and antiepileptic medication use. RESULTS: One hundred forty-six patients (49% female) were followed up for a mean of 41 months after VNS implantation. Thirty-two percent of patients had partial epilepsy and 68% had generalized epilepsy. After VNS system implantation, seizure frequency was reduced in 91% of patients, seizure duration in 50%, postictal period in 49%, and antiepileptic medication use in 75%. There was no significant difference in age, sex, or duration of follow-up according to epilepsy type. Neither was there any significant difference in seizure frequency reduction, seizure duration, postictal period, medication use, overall clinical improvement, or improvement in quality of life based on an age ≥ or < 12 years or epilepsy type. CONCLUSIONS: Vagus nerve stimulation reduced both seizure frequency and antiepileptic medication use in the majority of pediatric patients regardless of sex, age cohort, or epilepsy type. Vagus nerve stimulation also reduced seizure duration and postictal period in approximately half of the pediatric patients. Contrary to expectation, children with partial epilepsy do not benefit from VNS at higher rates than those with generalized epilepsy.

Authors
Thompson, EM; Wozniak, SE; Roberts, CM; Kao, A; Anderson, VC; Selden, NR
MLA Citation
Thompson, EM, Wozniak, SE, Roberts, CM, Kao, A, Anderson, VC, and Selden, NR. "Vagus nerve stimulation for partial and generalized epilepsy from infancy to adolescence." Journal of neurosurgery. Pediatrics 10.3 (September 2012): 200-205.
PMID
22768964
Source
epmc
Published In
Journal of neurosurgery. Pediatrics
Volume
10
Issue
3
Publish Date
2012
Start Page
200
End Page
205
DOI
10.3171/2012.5.peds11489

Dual contrast perfusion MRI in a single imaging session for assessment of pediatric brain tumors.

Ferumoxytol, an iron nanoparticle used as an intravascular contrast agent for perfusion magnetic resonance imaging (MRI), has never been explored in the pediatric population. The purpose of this prospective study is to characterize the vascular and permeability properties of pediatric brain tumors using two contrast agents during a single imaging session: ferumoxytol for dynamic susceptibility weighted contrast (DSC) MRI and gadoteridol for dynamic contrast-enhanced (DCE) MRI. In a single imaging session, patients received intravenous ferumoxytol for DSC MRI followed by gadoteridol for DCE MRI. Relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), transfer coefficient (K(trans)), and extravascular extracellular space volume fraction (v(e)) of the brain lesions were calculated. Patients underwent serial imaging sessions over the course of 2 years. Of the 7 patients enrolled thus far, none has experienced an adverse event. Two patients with medulloblastoma were enrolled preoperatively. In the first, rCBV(max), rCBF, K(trans) max, and v(e) max values were 3.74, 3.12, 0.47 min (-1), and 0.08, respectively, while in the second patient, rCBV(max), rCBF, K(trans) max, and v(e) max values were 4.72, 3.47, 0.60 min(-1), and 0.05, respectively. Four patients were enrolled after new gadolinium enhancement was noted in the tumor resection cavity. In 80 % of these lesions, rCBV was <1 suggestive of pseudoprogression secondary to radiochemotherapy. These preliminary results demonstrate that use of ferumoxytol and gadoteridol contrast agents during a single imaging session is feasible, safe, and appears useful for assessing tumor perfusion and permeability characteristics in children.

Authors
Thompson, EM; Guillaume, DJ; Dósa, E; Li, X; Nazemi, KJ; Gahramanov, S; Hamilton, BE; Neuwelt, EA
MLA Citation
Thompson, EM, Guillaume, DJ, Dósa, E, Li, X, Nazemi, KJ, Gahramanov, S, Hamilton, BE, and Neuwelt, EA. "Dual contrast perfusion MRI in a single imaging session for assessment of pediatric brain tumors." Journal of neuro-oncology 109.1 (August 2012): 105-114.
PMID
22528798
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
109
Issue
1
Publish Date
2012
Start Page
105
End Page
114
DOI
10.1007/s11060-012-0872-x

The paradoxical effect of bevacizumab in the therapy of malignant gliomas.

Authors
Chamberlain, MC
MLA Citation
Chamberlain, MC. "The paradoxical effect of bevacizumab in the therapy of malignant gliomas." Neurology 77.8 (August 2011): 803-. (Letter)
PMID
21860011
Source
epmc
Published In
Neurology
Volume
77
Issue
8
Publish Date
2011
Start Page
803
DOI
10.1212/wnl.0b013e3182247068

Neuroform stent-assisted embolization of incidental anterior communicating artery aneurysms: long-term clinical and angiographic follow-up.

BACKGROUND: Anterior communicating artery (A-comm) aneurysm is one of the most common intracranial aneurysms. Treatments include neurosurgical clipping or endovascular embolization. OBJECTIVE: To retrospectively examine the long-term results of Neuroform stent-assisted coil embolization of incidental A-comms, with a focus on stent-associated stenosis, long-term angiographic aneurysm occlusion outcome, delayed stent-related thromboembolus, subsequent subarachnoid hemorrhage from the treated aneurysm, and procedural complications. METHODS: Between January 7, 2003 and June 16, 2009, 44 Neuroform stents were placed as an adjunct to embolization of A-comms. Patient charts were reviewed retrospectively. Angiographic follow-up of at least 3 months (up to 6.5 years, mean 65 weeks) was available for 33 patients. Aneurysm occlusion success was determined using the Raymond classification for aneurysm remnants. RESULTS: Referencing the last angiogram in the follow-up course, complete occlusion, dog-ear residual, residual neck, and residual aneurysm were found in 24, 2, 3, and 4 patients, respectively. Stenosis (45% and asymptomatic) of the artery where the stent had been placed was found in 1 patient. One patient had delayed transient ischemic attack after dual antiplatelet therapy was stopped prematurely. Retreatment based on the presence of residual aneurysm was performed or recommended in 2 patients. In 2 patients with residual or recurrent aneurysm filling, their age or clinical condition did not warrant retreatment. CONCLUSION: Neuroform stent-assisted embolization provides long-term control of A-comms with a low incidence of aneurysm growth after treatment. The need for retreatment is uncommon, and retreatment is safe if performed. Subsequent bleeding from treated aneurysms was not observed in this study.

Authors
Raslan, AM; Oztaskin, M; Thompson, EM; Dogan, A; Petersen, B; Nesbit, G; Lee, DS; Barnwell, SL
MLA Citation
Raslan, AM, Oztaskin, M, Thompson, EM, Dogan, A, Petersen, B, Nesbit, G, Lee, DS, and Barnwell, SL. "Neuroform stent-assisted embolization of incidental anterior communicating artery aneurysms: long-term clinical and angiographic follow-up." Neurosurgery 69.1 (July 2011): 27-37.
PMID
21311379
Source
epmc
Published In
Neurosurgery
Volume
69
Issue
1
Publish Date
2011
Start Page
27
End Page
37
DOI
10.1227/neu.0b013e31820edbb6

Correlation of MRI sequences to assess progressive glioblastoma multiforme treated with bevacizumab.

In the context of bevacizumab therapy for the treatment of progressive malignant gliomas, it is currently unclear how different magnetic resonance imaging (MRI) sequences correlate with each other over time. The objective of this study was to determine if a reliable and predictable relationship over time exists between post-gadolinium based contrast agent T1-weighted (T1 + GBCA), T2-weighted, and FLAIR MRI in patients with progressive glioblastoma multiforme (GBM) receiving bevacizumab and chemotherapy. The MRI lesion volumes of 10 patients with progressive GBM that received bevacizumab plus chemotherapy were manually calculated by two independent reviewers. T2 and FLAIR volumes were analyzed by analysis of covariance (ANCOVA) as a function of T1 + GBCA lesion enhancement volume, reviewer, and time interval between MRI acquisitions. Pearson product moment correlation (r) was used to compare pre and post treatment volumes for the group of 10 patients and for each individual patient over their treatment course. ANCOVA demonstrated a significant association between T1 + GBCA and T2-weighted volumes (P = 0.0006) and between T1 + GBCA and FLAIR volumes (P < 0.0001). These associations remained constant over time. The correlation between T1 + GBCA and both T2-weighted and FLAIR volumes improved after bevacizumab treatment. Individual correlations between T1 + GBCA and FLAIR were strong (r ≥ 0.63) with one exception, while correlations between T1 + GBCA and T2 were more variable (r = 0.18-0.99). These findings suggest that FLAIR MRI should be evaluated in addition to T1 + GBCA MRI when evaluating GBM responses.

Authors
Thompson, EM; Dosa, E; Kraemer, DF; Neuwelt, EA
MLA Citation
Thompson, EM, Dosa, E, Kraemer, DF, and Neuwelt, EA. "Correlation of MRI sequences to assess progressive glioblastoma multiforme treated with bevacizumab." Journal of neuro-oncology 103.2 (June 2011): 353-360.
PMID
20848300
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
103
Issue
2
Publish Date
2011
Start Page
353
End Page
360
DOI
10.1007/s11060-010-0397-0

Vagal nerve stimulator infection: a lead-salvage protocol.

OBJECT: Vagal nerve stimulator (VNS) hardware infections are fraught with difficult management decisions. As with most implanted medical device-related infections, standard practice traditionally involves complete hardware removal, systemic antibiotic therapy, and subsequent reimplantation of the device. To avoid the potential morbidity of 2 repeat left carotid sheath surgical dissections, the authors have implemented a clinical protocol for managing VNS infections that involves generator removal and antibiotic therapy without lead removal. METHODS: A prospective, single-surgeon database was compared with hospital billing records to identify patients who underwent primary implantation or reimplantation of a VNS lead, generator, or both, from January 2001 to May 2010, at Oregon Health & Science University. From these records, the authors identified patients with VNS hardware infections and characterized their management, using a lead salvage protocol. RESULTS: In their review, the authors found a matching cohort of 206 children (age 3 months-17 years) who met the inclusion criteria. These children underwent 258 operations (including, in some children, multiple operations for generator end of life and/or lead malfunction). Six children experienced a single postimplantation infection (2.3% of the 258 operative cases), and no child experienced repeated infection. A lead-salvage protocol was used in 4 of 6 infected patients and was successful in 3 (75%), with clinical follow-up ranging from 10 months to 7.5 years. The fourth patient subsequently underwent lead removal and later reimplantation in standard fashion, with no adverse sequelae. CONCLUSIONS: Vagal nerve stimulator lead salvage is a safe and potentially advantageous strategy in the management of VNS-related infection. Further study is necessary to validate appropriate patient selection, success rates, and risks of this approach.

Authors
Wozniak, SE; Thompson, EM; Selden, NR
MLA Citation
Wozniak, SE, Thompson, EM, and Selden, NR. "Vagal nerve stimulator infection: a lead-salvage protocol." Journal of neurosurgery. Pediatrics 7.6 (June 2011): 671-675.
PMID
21631207
Source
epmc
Published In
Journal of neurosurgery. Pediatrics
Volume
7
Issue
6
Publish Date
2011
Start Page
671
End Page
675
DOI
10.3171/2011.4.peds10556

Rapid intra-arterial thrombolysis in stent-associated retinal artery occlusion.

Authors
Thompson, EM; Egan, RA; Nesbit, GM; Hills, WL
MLA Citation
Thompson, EM, Egan, RA, Nesbit, GM, and Hills, WL. "Rapid intra-arterial thrombolysis in stent-associated retinal artery occlusion." Journal of vascular and interventional radiology : JVIR 22.3 (March 2011): 410-412. (Letter)
PMID
21353992
Source
epmc
Published In
JVIR: Journal of Vascular and Interventional Radiology
Volume
22
Issue
3
Publish Date
2011
Start Page
410
End Page
412
DOI
10.1016/j.jvir.2010.10.034

Skull-fixated fiducial markers improve accuracy in staged frameless stereotactic epilepsy surgery in children.

OBJECT: Surgery to monitor and resect epileptogenic foci may be undertaken in 2 stages, providing an opportunity to use skull-fixated fiducials implanted during the first stage to improve the accuracy of cortical resection during the second stage. This study compared the intrinsic accuracy of skin-based and skull-fixated fiducial markers in registering frameless stereotaxy during pediatric epilepsy surgery. To the authors' knowledge, these modalities of registration have not previously been directly compared in this population. METHODS: The authors undertook a retrospective review of pediatric patients who underwent resection of epileptogenic foci in 2 stages with frameless stereotactic assistance, performed by a single surgeon at Oregon Health & Science University. For the first stage (subdural grid implantation), 9 skin fiducial markers were used to register anatomical data in a frameless stereotactic station. Intraoperatively, four 3-mm screws were placed circumferentially around the craniotomy. Postoperatively, thin-slice brain MR and CT images were obtained and fused. For the second stage, the 4 screws were used as fiducial markers to register the stereotactic anatomical data. For both stages, accuracy (difference in millimeters from zero of the manual fiducial registration compared with the computer model) was determined using navigation software. The intrinsic accuracy of these 2 methods of fiducial registration was compared using a paired Student t-test. RESULTS: Between 2004 and 2009, 40 pediatric patients with epilepsy underwent frameless stereotactic surgical procedures. Fourteen patients who had 2-stage procedures using skin-based and skull-fixated registration with complete accuracy data were included in this retrospective review. Mean registration error was significantly lower using skull-fixated fiducials (1.35 mm, 95% CI 1.09-1.60 mm) than using skin-based fiducials (1.85 mm, 95% CI 1.56-2.13 mm; p = 0.0016). CONCLUSIONS: A significantly higher degree of accuracy was achieved using 4 skull-fixated fiducials compared with using 9 skin-based fiducials. This simple and accurate method for registering frameless stereotactic anatomical data does not involve the potential time, expense, discomfort, and morbidity of extraoperative skull-fixated fiducial placement. The method described in this paper could also be extrapolated to other planned 2-stage cranial surgical procedures such as combined skull base approaches.

Authors
Thompson, EM; Anderson, GJ; Roberts, CM; Hunt, MA; Selden, NR
MLA Citation
Thompson, EM, Anderson, GJ, Roberts, CM, Hunt, MA, and Selden, NR. "Skull-fixated fiducial markers improve accuracy in staged frameless stereotactic epilepsy surgery in children." Journal of neurosurgery. Pediatrics 7.1 (January 2011): 116-119.
PMID
21194296
Source
epmc
Published In
Journal of neurosurgery. Pediatrics
Volume
7
Issue
1
Publish Date
2011
Start Page
116
End Page
119
DOI
10.3171/2010.10.peds10352

The paradoxical effect of bevacizumab in the therapy of malignant gliomas.

One rationale behind the use of agents that inhibit vascular endothelial growth factor in the therapy of primary CNS malignancies is based upon the concept that normalization of tumor vasculature with a decrease in tumor interstitial pressure will improve access of cytoreductive drugs and improve radiotherapy efficacy due to increased oxygen delivery. However, several studies have raised the concern that these agents may both rapidly restore the low permeability characteristics of the blood-brain barrier and counteract the beneficial effect of pseudoprogression. The result may be decreased therapeutic efficacy while increasing infiltration by co-opting normal vessels. In this discussion, we examine both histologic and radiographic tumor progression in the context of antiangiogenic agents. Issues dealing with the safety of bevacizumab (Avastin®, Genentech, South San Francisco, CA) and its potential to decrease efficacy of standard radiochemotherapy when used to treat patients with newly diagnosed malignant glioma are emphasized.

Authors
Thompson, EM; Frenkel, EP; Neuwelt, EA
MLA Citation
Thompson, EM, Frenkel, EP, and Neuwelt, EA. "The paradoxical effect of bevacizumab in the therapy of malignant gliomas." Neurology 76.1 (January 2011): 87-93.
PMID
21205697
Source
epmc
Published In
Neurology
Volume
76
Issue
1
Publish Date
2011
Start Page
87
End Page
93
DOI
10.1212/wnl.0b013e318204a3af

Transendoscopic intraoperative recording of gelastic seizures from a hypothalamic hamartoma.

OBJECT: The differential diagnosis of hypothalamic masses in children includes hamartomas, which are associated with gelastic seizures and endocrine dysfunction. The purpose of this study was to utilize transendoscopic electroencephalography (EEG) recording at the time of tissue biopsy to further assist in diagnosis, determination of prognosis, and treatment planning. METHODS: We present the case of an infant with gelastic seizures and a large hypothalamic mass lesion. Despite a clinical and radiographic presentation typical of hypothalamic hamartoma (HH), slight growth on serial imaging raised concern for a diagnosis of intrinsic neoplasm. Biopsy of the lesion was recommended. RESULTS: Transventricular, endoscopic biopsy, was undertaken, with concurrent intraoperative, transendoscopic EEG recording using a standard epilepsy depth recording macroelectrode. Numerous electrographic seizures were recorded. Histopathology revealed a HH. CONCLUSION: This is the first report of intraoperative macroelectrode recording of electrographic seizures transendoscopically from a HH. This technique may prove useful for diagnosis, prognosis and treatment planning, as well as to guide transendoscopic therapeutic interventions for HH.

Authors
Roberts, CM; Thompson, EM; Selden, NR
MLA Citation
Roberts, CM, Thompson, EM, and Selden, NR. "Transendoscopic intraoperative recording of gelastic seizures from a hypothalamic hamartoma." Pediatric neurosurgery 47.2 (January 2011): 147-151.
PMID
21921578
Source
epmc
Published In
Pediatric neurosurgery
Volume
47
Issue
2
Publish Date
2011
Start Page
147
End Page
151
DOI
10.1159/000330547

Treatment with bevacizumab plus carboplatin for recurrent malignant glioma.

To estimate overall survival (OS), progression-free survival (PFS), imaging responses, and toxicities of bevacizumab plus carboplatin for the treatment of recurrent malignant glioma. The secondary objective was to estimate the agreement between postcontrast T1-weighted and T2-weighted magnetic resonance imaging.A retrospective analysis of 9 patients who received bevacizumab (10 mg/kg intravenously) and carboplatin (AUC 5 intravenously) for recurrent malignant glioma (World Health Organization grades III and IV) is presented. Eight of 9 patients received this regimen at first recurrence.The median age and Karnofsky performance score were 51 years and 70, respectively. For the 5 patients with grade III gliomas, the median PFS was 126 days, whereas median OS was not attained at 517 days of follow-up. Six-month PFS was 40%, whereas 6-month OS was 60%. For the 4 patients with grade IV gliomas, the median PFS was 216 days, whereas the median OS was not attained at 482 days of follow-up. Six-month PFS was 50%, whereas 6-month OS was 75%. The agreement between contrast-enhanced T1-weighted and T2-weighted images to determine recurrence was moderate (kappa=0.5714). Three patients had grade 3 and 4 toxicities including hyponatremia and thrombocytopenia.Patients who received the combination of bevacizumab plus carboplatin for recurrent malignant glioma had reasonable PFS, OS, and toxicities. The median OS in our series is promising at well over 1 year. Agreement between postcontrast T1- and T2-weighted images is only moderate in the context of bevacizumab therapy.

Authors
Thompson, EM; Dosa, E; Kraemer, DF; Neuwelt, EA
MLA Citation
Thompson, EM, Dosa, E, Kraemer, DF, and Neuwelt, EA. "Treatment with bevacizumab plus carboplatin for recurrent malignant glioma." Neurosurgery 67.1 (July 2010): 87-93.
PMID
20559095
Source
epmc
Published In
Neurosurgery
Volume
67
Issue
1
Publish Date
2010
Start Page
87
End Page
93
DOI
10.1227/01.neu.0000370918.51053.bc

Lumbar lipomyelomeningocele and sacrococcygeal teratoma in siblings: support for an alternative theory of spinal teratoma formation.

Sacrococcygeal teratomas may arise in association with regional developmental errors affecting the caudal embryonic segments and may originate within lumbosacral lipomas. It is therefore possible that sacrococcygeal teratomas and lumbosacral lipomas represent related disorders of embryogenesis. Accordingly, the authors report the cases of 2 siblings. The first child (female) was born with a mature Altman Type III sacrococcygeal teratoma that was resected when she was a neonate. Subsequently, a younger brother was found soon after birth to have an L-4-level lipomyelomeningocele and underwent partial resection and spinal cord untethering at 4 months of age. Although familial forms of each of these conditions have been reported, this is, to the authors' knowledge, the first reported occurrence of lipomyelomeningocele and sacrococcygeal teratoma in siblings. They propose that an inherited regional tendency to developmental error affecting the caudal embryonic segments was shared by these siblings and resulted in spinal teratoma formation in one of them.

Authors
Oliveria, SF; Thompson, EM; Selden, NR
MLA Citation
Oliveria, SF, Thompson, EM, and Selden, NR. "Lumbar lipomyelomeningocele and sacrococcygeal teratoma in siblings: support for an alternative theory of spinal teratoma formation." Journal of neurosurgery. Pediatrics 5.6 (June 2010): 626-629.
PMID
20515338
Source
epmc
Published In
Journal of neurosurgery. Pediatrics
Volume
5
Issue
6
Publish Date
2010
Start Page
626
End Page
629
DOI
10.3171/2010.2.peds09502

Successful ventricle to direct heart shunt placement as a salvage cerebrospinal fluid diversion technique. Case report.

The authors report a complex case in a 35-year-old woman who underwent shunt placement at birth for myelomeningocele. She had previously undergone more than 30 shunt revisions, with placement of the distal catheter in the peritoneum multiple times, and also in the pleura, the gall bladder, and the upper venous system. All shunts had failed and the possible placement sites were now anatomically hostile. A median sternotomy was performed as the next option. The catheter was placed directly into the appendage of the right atrium and secured with a pursestring suture. One month postoperatively, the patient presented with a large pericardial effusion after the distal catheter migrated out of the atrium and into the pericardial space. A repeat sternotomy was performed to drain the pericardial CSF collection. The catheter was reinserted into the atrial appendage, and a tunnel was created in the atrial wall to fix the device more securely. At 1 year postoperatively, the patient had no further symptoms of shunt obstruction or cardiac tamponade, and imaging studies suggested that the shunt system was functional. The authors report the first successful ventricle to direct heart shunt in an adult.

Authors
Thompson, EM; Giles, SG; Song, HK; Litvack, ZN; Golshani, KJ; Nemecek, AN
MLA Citation
Thompson, EM, Giles, SG, Song, HK, Litvack, ZN, Golshani, KJ, and Nemecek, AN. "Successful ventricle to direct heart shunt placement as a salvage cerebrospinal fluid diversion technique. Case report." Journal of neurosurgery. Pediatrics 3.6 (June 2009): 521-524.
PMID
19485739
Source
epmc
Published In
Journal of neurosurgery. Pediatrics
Volume
3
Issue
6
Publish Date
2009
Start Page
521
End Page
524
DOI
10.3171/2009.2.peds08332

Intracranial leptomeningeal metastasis from thymic carcinoma: case report and review.

BACKGROUND: Thymic carcinoma is an uncommon malignant tumor of the anterior mediastinum. Meningeal metastasis from this type of neoplasm is extraordinarily rare and the prognosis is abysmal. CASE DESCRIPTION: This article presents the case of a 45-year-old man with known metastatic thymic carcinoma who presented with intractable headaches. An MRI scan was highly suggestive of a meningioma, and it was initially suspected that this patient had 2 primary tumors. Surgical resection of the mass both demonstrated a metastatic thymic lesion and ameliorated the patient's quality of life. CONCLUSION: The authors report a case of intracranial meningeal metastasis from a lymphoepithelioma-like poorly differentiated metastatic thymic carcinoma, which was treated by resection and WBRT. A review of the current literature revealed no other cases of this uncommon alhistologic subtype of thymic carcinoma metastatic to the cranium. The incidence, histologic classification of subtypes, and treatment are discussed. This case also illustrates the importance of maintaining a high degree of suspicion for a metastasis in patients with known primary malignancy who present with an MRI highly suspicious for meningioma.

Authors
Thompson, EM; Sather, MD; Reyes, CA; Long, DJ
MLA Citation
Thompson, EM, Sather, MD, Reyes, CA, and Long, DJ. "Intracranial leptomeningeal metastasis from thymic carcinoma: case report and review." Surgical neurology 68.2 (August 2007): 233-238. (Review)
PMID
17537485
Source
epmc
Published In
World Neurosurgery
Volume
68
Issue
2
Publish Date
2007
Start Page
233
End Page
238
DOI
10.1016/j.surneu.2006.08.079

Cell cycle progression in G1 and S phases is CCR4 dependent following ionizing radiation or replication stress in Saccharomyces cerevisiae.

To identify new nonessential genes that affect genome integrity, we completed a screening for diploid mutant Saccharomyces cerevisiae strains that are sensitive to ionizing radiation (IR) and found 62 new genes that confer resistance. Along with those previously reported (Bennett et al., Nat. Genet. 29:426-434, 2001), these genes bring to 169 the total number of new IR resistance genes identified. Through the use of existing genetic and proteomic databases, many of these genes were found to interact in a damage response network with the transcription factor Ccr4, a core component of the CCR4-NOT and RNA polymerase-associated factor 1 (PAF1)-CDC73 transcription complexes. Deletions of individual members of these two complexes render cells sensitive to the lethal effects of IR as diploids, but not as haploids, indicating that the diploid G1 cell population is radiosensitive. Consistent with a role in G1, diploid ccr4Delta cells irradiated in G1 show enhanced lethality compared to cells exposed as a synchronous G2 population. In addition, a prolonged RAD9-dependent G1 arrest occurred following IR of ccr4Delta cells and CCR4 is a member of the RAD9 epistasis group, thus confirming a role for CCR4 in checkpoint control. Moreover, ccr4Delta cells that transit S phase in the presence of the replication inhibitor hydroxyurea (HU) undergo prolonged cell cycle arrest at G2 followed by cellular lysis. This S-phase replication defect is separate from that seen for rad52 mutants, since rad52Delta ccr4Delta cells show increased sensitivity to HU compared to rad52Delta or ccr4Delta mutants alone. These results indicate that cell cycle transition through G1 and S phases is CCR4 dependent following radiation or replication stress.

Authors
Westmoreland, TJ; Marks, JR; Olson, JA; Thompson, EM; Resnick, MA; Bennett, CB
MLA Citation
Westmoreland, TJ, Marks, JR, Olson, JA, Thompson, EM, Resnick, MA, and Bennett, CB. "Cell cycle progression in G1 and S phases is CCR4 dependent following ionizing radiation or replication stress in Saccharomyces cerevisiae." Eukaryot Cell 3.2 (April 2004): 430-446.
PMID
15075273
Source
pubmed
Published In
Eukaryotic cell
Volume
3
Issue
2
Publish Date
2004
Start Page
430
End Page
446

Anterior temporal lobectomy for complex partial seizures: Evaluation, results, and long-term follow-up in 100 cases

We report evaluation and results in 100 patients who had undergone anterior temporal lobectomy for intractable complex partial seizures. Average follow-up was 9.0 years (range, 2 to 21 years). In the 2nd postoperative year, 63% were seizure free, 16% were significantly improved, and 21% were considered not significantly improved. Mean number of seizures in the last group was 27% of preoperative levels. Surgical results did not change significantly in subsequent postoperative years; good outcomes tended to persist over the longer term. We also examined the utility of continuous depth electrode monitoring in the evaluation of patients with independent bitemporal interictal epileptiform activity. Despite limited numbers of subjects in this category, there was a trend toward improved surgical outcome when such subjects were evaluated with depth electrodes.

Authors
Walczak, TS; Radtke, RA; McNamara, JO; Lewis, DV; Luther, JS; Thompson, E; Wilson, WP; Friedman, AH; Nashold, BS
MLA Citation
Walczak, TS, Radtke, RA, McNamara, JO, Lewis, DV, Luther, JS, Thompson, E, Wilson, WP, Friedman, AH, and Nashold, BS. "Anterior temporal lobectomy for complex partial seizures: Evaluation, results, and long-term follow-up in 100 cases." Neurology 40.3 (1990): 413-418.
Source
scival
Published In
Neurology
Volume
40
Issue
3
Publish Date
1990
Start Page
413
End Page
418
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Research Areas:

  • Brain Neoplasms
  • Neoplasm Metastasis
  • Neoplasm Proteins
  • Neoplasm Recurrence, Local
  • Neoplasms, Experimental
  • Neoplasms, Nerve Tissue
  • Spine--Abnormalities--Surgery