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Kimon Bekelis, Joanna S. Kerley-Hamilton, Amy Teegarden, Craig R. Tomlinson, Rachael Kuintzle, Nathan Simmons, Robert J. Singer, David W. Roberts, Manolis Kellis and David A. Hendrix

OBJECTIVE

The molecular mechanisms behind cerebral aneurysm formation and rupture remain poorly understood. In the past decade, microRNAs (miRNAs) have been shown to be key regulators in a host of biological processes. They are noncoding RNA molecules, approximately 21 nucleotides long, that posttranscriptionally inhibit mRNAs by attenuating protein translation and promoting mRNA degradation. The miRNA and mRNA interactions and expression levels in cerebral aneurysm tissue from human subjects were profiled.

METHODS

A prospective case-control study was performed on human subjects to characterize the differential expression of mRNA and miRNA in unruptured cerebral aneurysms in comparison with control tissue (healthy superficial temporal arteries [STA]). Ion Torrent was used for deep RNA sequencing. Affymetrix miRNA microarrays were used to analyze miRNA expression, whereas NanoString nCounter technology was used for validation of the identified targets.

RESULTS

Overall, 7 unruptured cerebral aneurysm and 10 STA specimens were collected. Several differentially expressed genes were identified in aneurysm tissue, with MMP-13 (fold change 7.21) and various collagen genes (COL1A1, COL5A1, COL5A2) being among the most upregulated. In addition, multiple miRNAs were significantly differentially expressed, with miR-21 (fold change 16.97) being the most upregulated, and miR-143–5p (fold change −11.14) being the most downregulated. From these, miR-21, miR-143, and miR-145 had several significantly anticorrelated target genes in the cohort that are associated with smooth muscle cell function, extracellular matrix remodeling, inflammation signaling, and lipid accumulation. All these processes are crucial to the pathophysiology of cerebral aneurysms.

CONCLUSIONS

This analysis identified differentially expressed genes and miRNAs in unruptured human cerebral aneurysms, suggesting the possibility of a role for miRNAs in aneurysm formation. Further investigation for their importance as therapeutic targets is needed.

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Kimon Bekelis, Symeon Missios, Todd A. MacKenzie, Atman Desai, Adina Fischer, Nicos Labropoulos and David W. Roberts

Object

Precise delineation of individualized risks of morbidity and mortality is crucial in decision making in cerebrovascular neurosurgery. The authors attempted to create a predictive model of complications in patients undergoing cerebral aneurysm clipping (CAC).

Methods

The authors performed a retrospective cohort study of patients who had undergone CAC in the period from 2005 to 2009 and were registered in the Nationwide Inpatient Sample (NIS) database. A model for outcome prediction based on preoperative individual patient characteristics was developed.

Results

Of the 7651 patients in the NIS who underwent CAC, 3682 (48.1%) had presented with unruptured aneurysms and 3969 (51.9%) with subarachnoid hemorrhage. The respective inpatient postoperative risks for death, unfavorable discharge, stroke, treated hydrocephalus, cardiac complications, deep vein thrombosis, pulmonary embolism, and acute renal failure were 0.7%, 15.3%, 5.3%, 1.5%, 1.3%, 0.6%, 2.0%, and 0.1% for those with unruptured aneurysms and 11.5%, 52.8%, 5.5%, 39.2%, 1.7%, 2.8%, 2.7%, and 0.8% for those with ruptured aneurysms. Multivariate analysis identified risk factors independently associated with the above outcomes. A validated model for outcome prediction based on individual patient characteristics was developed. The accuracy of the model was estimated using the area under the receiver operating characteristic curve, and it was found to have good discrimination.

Conclusions

The featured model can provide individualized estimates of the risks of postoperative complications based on preoperative conditions and can potentially be used as an adjunct in decision making in cerebrovascular neurosurgery.

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Symeon Missios, Kimon Bekelis and David W. Roberts

Paul of Aegina (625–690 AD) was born on the island of Aegina and was one of the most prominent physician-writers of the Byzantine Empire. His work Epitome of Medicine, comprised of 7 books, was a comprehensive compendium of the medical and surgical knowledge of his time and was subsequently translated into multiple languages. Paul of Aegina made valuable contributions to neurosurgical subjects and described procedures for the treatment of nerve injuries, hydrocephalus, and fractures of the skull and spine. His work combined the ancient knowledge of Hippocrates and Galen with contemporary medical observations and served as a bridge between Byzantine and Arabic medicine. He is considered to be one of the great ancient Greek medical writers and his work has influenced the subsequent evolution of Western European and Arab medicine. This paper provides an account of his contribution to the management of neurosurgical pathologies during the Byzantine era, as described in his medical compendium, Epitome of Medicine.

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Kimon Bekelis, Atman Desai, Alex Kotlyar, Vijay Thadani, Barbara C. Jobst, Krzysztof Bujarski, Terrance M. Darcey and David W. Roberts

Object

Intracranial monitoring for epilepsy has been proven to enhance diagnostic accuracy and provide localizing information for surgical treatment of intractable seizures. The authors investigated the usefulness of hippocampal depth electrodes in the era of more advanced imaging techniques.

Methods

Between 1988 and 2010, 100 patients underwent occipitotemporal hippocampal depth electrode (OHDE) implantation as part of invasive seizure monitoring, and their charts were retrospectively reviewed. The authors' technique involved the stereotactically guided (using the Leksell model G frame) implantation of a 12-contact depth electrode directed along the long axis of the hippocampus, through an occipital twist drill hole.

Results

Of the 100 patients (mean age 35.0 years [range 13–58 years], 51% male) who underwent intracranial investigation, 84 underwent resection of the seizure focus. Magnetic resonance imaging revealed mesial temporal sclerosis (MTS) in 27% of patients, showed abnormal findings without MTS in 55% of patients, and showed normal findings in 18% of patients. One patient developed a small asymptomatic occipital hemorrhage around the electrode tract. The use of OHDEs enabled epilepsy resection in 45.7% of patients who eventually underwent standard or selective temporal lobe resection. The hippocampal formation was spared during surgery because data obtained from the depth electrodes showed no or only secondary involvement in 14% of patients with preoperative temporal localization. The use of OHDEs prevented resections in 12% of patients with radiographic evidence of MTS. Eighty-three percent of patients who underwent resection had Engel Class I (68%) or II (15%) outcome at 2 years of follow-up.

Conclusions

The use of OHDEs for intracranial epilepsy monitoring has a favorable risk profile, and in the authors' experience it proved to be a valuable component of intracranial investigation. The use of OHDEs can provide the sole evidence for resection of some epileptogenic foci and can also result in hippocampal sparing or prevent likely unsuccessful resection in other patients.

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Kimon Bekelis, Tarek A. Radwan, Atman Desai, Ziev B. Moses, Vijay M. Thadani, Barbara C. Jobst, Krzysztof A. Bujarski, Terrance M. Darcey and David W. Roberts

Object

Intracranial monitoring for epilepsy has been proven to enhance diagnostic accuracy and provide localizing information for surgical treatment of intractable seizures. The authors investigated their experience with interhemispheric grid electrodes (IHGEs) to assess the hypothesis that they are feasible, safe, and useful.

Methods

Between 1992 and 2010, 50 patients underwent IHGE implantation (curvilinear double-sided 2 × 8 or 3 × 8 grids) as part of arrays for invasive seizure monitoring, and their charts were retrospectively reviewed.

Results

Of the 50 patients who underwent intracranial investigation with IHGEs, 38 eventually underwent resection of the seizure focus. These 38 patients had a mean age of 30.7 years (range 11–58 years), and 63% were males. Complications as a result of IHGE implantation consisted of transient leg weakness in 1 patient. Of all the patients who underwent resective surgery, 21 (55.3%) had medial frontal resections, 9 of whom (43%) had normal MRI results. Localization in all of these cases was possible only because of data from IHGEs, and the extent of resection was tailored based on these data. Of the 17 patients (44.7%) who underwent other cortical resections, IHGEs were helpful in excluding medial seizure onset. Twelve patients did not undergo resection because of nonlocalizable or multifocal disease; in 2 patients localization to the motor cortex precluded resection. Seventy-one percent of patients who underwent resection had Engel Class I outcome at the 2-year follow-up.

Conclusions

The use of IHGEs in intracranial epilepsy monitoring has a favorable risk profile and in the authors' experience proved to be a valuable component of intracranial investigation, providing the sole evidence for resection of some epileptogenic foci.

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Kimon Bekelis, Tarek A. Radwan, Atman Desai and David W. Roberts

Object

Frameless stereotactic brain biopsy has become an established procedure in many neurosurgical centers worldwide. Robotic modifications of image-guided frameless stereotaxy hold promise for making these procedures safer, more effective, and more efficient. The authors hypothesized that robotic brain biopsy is a safe, accurate procedure, with a high diagnostic yield and a safety profile comparable to other stereotactic biopsy methods.

Methods

This retrospective study included 41 patients undergoing frameless stereotactic brain biopsy of lesions (mean size 2.9 cm) for diagnostic purposes. All patients underwent image-guided, robotic biopsy in which the SurgiScope system was used in conjunction with scalp fiducial markers and a preoperatively selected target and trajectory. Forty-five procedures, with 50 supratentorial targets selected, were performed.

Results

The mean operative time was 44.6 minutes for the robotic biopsy procedures. This decreased over the second half of the study by 37%, from 54.7 to 34.5 minutes (p < 0.025). The diagnostic yield was 97.8% per procedure, with a second procedure being diagnostic in the single nondiagnostic case. Complications included one transient worsening of a preexisting deficit (2%) and another deficit that was permanent (2%). There were no infections.

Conclusions

Robotic biopsy involving a preselected target and trajectory is safe, accurate, efficient, and comparable to other procedures employing either frame-based stereotaxy or frameless, nonrobotic stereotaxy. It permits biopsy in all patients, including those with small target lesions. Robotic biopsy planning facilitates careful preoperative study and optimization of needle trajectory to avoid sulcal vessels, bridging veins, and ventricular penetration.

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Atman Desai, Kimon Bekelis, Terrance M. Darcey and David W. Roberts

Intracranial electroencephalography monitoring of the insula is an important tool in the investigation of the insula in medically intractable epilepsy and has been shown to be safe and reliable. Several methods of placing electrodes for insular coverage have been reported and include open craniotomy as well as stereotactic orthogonal and stereotactic anterior and posterior oblique trajectories. The authors review each of these techniques with respect to current concepts in insular epilepsy.

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Kimon Bekelis, Pablo A. Valdés, Kadir Erkmen, Frederic Leblond, Anthony Kim, Brian C. Wilson, Brent T. Harris, Keith D. Paulsen and David W. Roberts

Object

Complete resection of skull base meningiomas provides patients with the best chance for a cure; however, surgery is frequently difficult given the proximity of lesions to vital structures, such as cranial nerves, major vessels, and venous sinuses. Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative assessment of protoporphyrin IX (PpIX) fluorescence following the exogenous administration of 5-aminolevulinic acid (ALA) has demonstrated utility in malignant glioma resection but limited use in meningiomas. Here the authors demonstrate the use of ALA-induced PpIX fluorescence guidance in resecting a skull base meningioma and elaborate on the advantages and disadvantages provided by both quantitative and qualitative fluorescence methodologies in skull base meningioma resection.

Methods

A 52-year-old patient with a sphenoid wing WHO Grade I meningioma underwent tumor resection as part of an institutional review board–approved prospective study of fluorescence-guided resection. A surgical microscope modified for fluorescence imaging was used for the qualitative assessment of visible fluorescence, and an intraoperative probe for in situ fluorescence detection was utilized for quantitative measurements of PpIX. The authors assessed the detection capabilities of both the qualitative and quantitative fluorescence approaches.

Results

The patient harboring a sphenoid wing meningioma with intraorbital extension underwent radical resection of the tumor with both visibly and nonvisibly fluorescent regions. The patient underwent a complete resection without any complications. Some areas of the tumor demonstrated visible fluorescence. The quantitative probe detected neoplastic tissue better than the qualitative modified surgical microscope. The intraoperative probe was particularly useful in areas that did not reveal visible fluorescence, and tissue from these areas was confirmed as tumor following histopathological analysis.

Conclusions

Fluorescence-guided resection may be a useful adjunct in the resection of skull base meningiomas. The use of a quantitative intraoperative probe to detect PpIX concentration allows more accurate determination of neoplastic tissue in meningiomas than visible fluorescence and is readily applicable in areas, such as the skull base, where complete resection is critical but difficult because of the vital structures surrounding the pathology.