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Paul House

The implantation of deep brain stimulator electrodes is associated with infrequent complications. These complications are consistent across prospective trials and include infection, skin erosion, hemorrhage, and lead misplacement. Nuances of surgical technique can be used to minimize the risk of these commonly noted complications. Several of these technical nuances are highlighted in this video submission.

The video can be found here: https://youtu.be/GL09W9p013g.

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Paul A. House and William T. Couldwell

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Paul A. House, Joel D. MacDonald, Patrick A. Tresco and Richard A. Normann

Object

Researchers at The Center for Neural Interfaces at the University of Utah have designed and produced a silicon-based high-density microelectrode array that has been used successfully in mammalian models. The authors investigate the ability to transfer array insertion techniques to humans and examine the acute response of human cortical tissue to array implantation.

Methods

Six patients who were scheduled to undergo temporal lobectomy surgery were enrolled in an Institutional Review Board–approved protocol. Before the patients underwent lateral temporal cortical resection, one or two high-density microelectrode arrays were implanted in each individual by using a pneumatic insertion device. Cortical tissue was then excised and preserved in formalin. The specimens were sectioned and stained for histological examination.

Pneumatic insertion of a microelectrode array into human cortex in the operating room was feasible. There were no clinical complications associated with implantation and no evidence of significant insertion-related hemorrhage. Tissue responses ranged from mild cortical deformity to small focal hemorrhages several millimeters below the electrode tines. Based on initial results, the insertion device was modified. A footplate that mechanically isolates a small area of cortex and a calibrated micromanipulator were added to improve the reproducibility of insertion.

Conclusions

A high-density microelectrode array designed to function as a direct cortical interface device can be implanted into human cortical tissue without acute clinical complications. Further modifications to the insertion device and array design are ongoing and future work will assess the functional significance of the tissue reactions observed.

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Spencer S. Kellis, Paul A. House, Kyle E. Thomson, Richard Brown and Bradley Greger

Object

The goal of this study was to determine whether a nonpenetrating, high-density microwire array could provide sufficient information to serve as the interface for decoding motor cortical signals.

Methods

Arrays of nonpenetrating microwires were implanted over the human motor cortex in 2 patients. The patients performed directed stereotypical reaching movements in 2 directions. The resulting data were used to determine whether the reach direction could be distinguished through a frequency power analysis.

Results

Correlation analysis revealed decreasing signal correlation with distance. The gamma-band power during motor planning allowed binary classification of gross directionality in the reaching movements. The degree of power change was correlated to the underlying gyral pattern.

Conclusions

The nonpenetrating microwire platform showed good potential for allowing differentiated signals to be recorded with high spatial fidelity without cortical penetration.

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Randy L. Jensen, David Gillespie, Paul House, Lester Layfield and Clough Shelton

Object. Endolymphatic sac (ELS) tumors are low-grade malignancies of the temporal bone that are associated with von Hippel—Lindau (VHL) disease but can also occur sporadically. The VHL gene product VHL protein is important in the regulation of hypoxia inducible factor (HIF)-1α, which controls expression of molecules that are important in angiogenesis and cell metabolism. In this study the authors examine the role of VHL and HIF-1 in ELS tumors.

Methods. The ELS tumors from three patients were examined using the following method: DNA from tumor tissue was isolated, amplified by polymerase chain reaction and the VHL gene sequence was compared with the known wild-type sequence. Loss of heterozygosity (LOH) studies were performed to confirm the sequencing data. Immunohistochemical evaluation for VHL, HIF-1α, vascular endothelial growth factor (VEGF), and carbonic anhydrase IX (CA IX) was performed. Snap-frozen tumor tissue was examined using Western blot and HIF-1 immunoassays for HIF-1α and VHL expression.

Two patients had sporadic ELS tumors and the other one suffered from VHL disease. Results of VHL gene sequencing were normal in the tissue derived from the sporadic ELS tumors. The ELS tumor, pheochromocytoma, and spinal hemangioblastoma were heterozygous for the same C-to-A transversion found in the germline carried by the patient with VHL disease. No LOH was detected in the tumor tissue obtained in the patient with VHL disease. Expression of HIF-1α, VEGF, and CA IX evaluated using immunohistochemical studies was elevated in the VHL-associated tumors. Nevertheless, Western blots and immunoassays for HIF-1α did not show elevated expression in these tumors.

Conclusions. The sporadic and VHL disease—associated ELS tumors in this study had normal VHL-mediated HIF-1 regulation. This is a result of normal VHL gene expression in the case of the sporadic ELS tumor. In the VHL-associated ELS tumor, this is due to one normal copy of the VHL gene and adequate VHL gene expression.

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Paul House, Karen L. Salzman, Anne G. Osborn, Joel D. MacDonald, Randy L. Jensen and William T. Couldwell

Object. Dilations of brain perivascular spaces (PVSs), also known as Virchow—Robin spaces, are routinely identified on magnetic resonance imaging studies of the brain and recognized as benign normal variants. Giant dilations occur only rarely and can be easily misdiagnosed as central nervous system tumors. The relevant surgical literature was reviewed to help establish indications for surgical intervention in these typically benign lesions.

Methods. Giant dilations of the PVSs in 12 patients who had undergone surgery for several different indications were identified. Both clinical and radiographic presentations of these patients were reviewed along with the surgical procedures.

Conclusions. Dilations of the PVSs can become giant lesions that may necessitate surgical intervention to relieve mass effect or hydrocephalus. The relationship of these lesions to neurological symptoms such as tremor and seizures remains unclear.

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Walavan Sivakumar, Michael Jensen, Julie Martinez, Michael Tanana, Nancy Duncan, Robert Hoesch, Jay K. Riva-Cambrin, Craig Kilburg, Safdar Ansari and Paul A. House

OBJECTIVE

Acute pain control after cranial surgery is challenging. Prior research has shown that patients experience inadequate pain control post-craniotomy. The use of oral medications is sometimes delayed because of postoperative nausea, and the use of narcotics can impair the evaluation of brain function and thus are used judiciously. Few nonnarcotic intravenous (IV) analgesics exist. The authors present the results of the first prospective study evaluating the use of IV acetaminophen in patients after elective craniotomy.

METHODS

The authors conducted a randomized, double-blinded, placebo-controlled investigation. Adults undergoing elective, supratentorial craniotomies between September 2013 and June 2015 were randomized into two groups. The experimental group received 1000 mg/100 ml IV acetaminophen every 8 hours for 48 hours. The placebo group received 100 ml of 0.9% normal saline on the same schedule. Both groups were also treated with a standardized pain control algorithm. The study was powered to detect a 30% difference in the primary outcome measures: narcotic consumption (morphine equivalents, ME) at 24 and 48 hours after surgery. Patient-reported pain scores immediately postoperatively and 48 hours after surgery were also recorded.

RESULTS

A total of 204 patients completed the trial. No significant differences were found in narcotic consumption between groups at either time point (in the treatment and placebo groups, respectively, at 24 hours: 84.3 ME [95% CI 70.2–98.4] and 85.5 ME [95% CI 73–97.9]; and at 48 hours: 123.5 ME [95% CI 102.9–144.2] and 134.2 ME [95% CI 112.1–156.3]). The difference in improvement in patient-reported pain scores between the treatment and placebo groups was significant (p < 0.001).

CONCLUSIONS

Patients who received postoperative IV acetaminophen after craniotomy did not have significantly decreased narcotic consumption but did experience significantly lower pain scores after surgery. The drug was well tolerated and safe in this patient population.

Clinical trial registration no.: NCT01948505 (clinicaltrials.gov)