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Eric M. Thompson, Kim J. Burchiel and Ahmed M. Raslan

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.

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Seth F. Oliveria, Eric M. Thompson and Nathan R. Selden

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.

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Susan E. Wozniak, Eric M. Thompson and Nathan R. Selden

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.

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Eric M. Thompson, Kate Wagner, Kassi Kronfeld and Nathan R. Selden

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.

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Eric M. Thompson, Lissa C. Baird and Nathan R. Selden

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.

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Eric M. Thompson, Gregory J. Anderson, Colin M. Roberts, Matthew A. Hunt and Nathan R. Selden

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.

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Jetan H. Badhiwala, Eric M. Thompson, Armando J. Lorenzo and Abhaya V. Kulkarni

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.

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Eric M. Thompson, Michael J. Strong, Garth Warren, Randy L. Woltjer and Nathan R. Selden

Object

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.

Methods

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.

Results

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).

Conclusions

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.

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Eric M. Thompson, Nathaniel L. Whitney, Y. Jeffrey Wu and Edward A. Neuwelt

Object

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 αv integrins with the monoclonal antibody intetumumab inhibits hypoxia-induced cellular stress responses.

Methods

Cells were grown at 21% and 1% O2 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), αv integrins, HIF-1α, and c-Myc.

Results

Both cell lines robustly expressed αv 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).

Conclusions

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 αv integrins represents a promising potential adjuvant modality in the treatment of medulloblastoma, particularly subtypes that metastasize and overexpress VEGF and c-Myc.