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Feng Xu, Hai Jin, Xingwang Yang, Xiao Sun, Yu Wang, Mengting Xu and Yingqun Tao

OBJECTIVE

The aim of this study was to determine whether a modified registration method could reduce registration error and postoperative electrode vector error and to analyze the method’s clinical significance in deep brain stimulation (DBS) surgery.

METHODS

The first part of the study involved a skull model, in which three registration methods were tested using the ROSA (robotic stereotactic assistance) system. In the second part, four registration methods were clinically tested in patients undergoing DBS surgery using the ROSA system. Thirty-three patients (65 sides, group I) underwent the conventional registration method 2E, and registration errors were recorded. Thirty-eight patients (75 sides, group II) underwent four types of modified registration methods including 2A, 2B, 2C, and 2D. Registration and electrode vector errors, intraoperative electrophysiological signal length (IESL), and DBS power-on voltage were recorded. The primary measure of efficacy was the change in the Unified Parkinson’s Disease Rating Scale (UPDRS) and UPDRS Part III scores from baseline to 10 weeks after surgery.

RESULTS

In the skull model, the registration error (mean ± SD) was 0.56 ± 0.11 mm for method 1A, 0.35 ± 0.11 mm for method 1B (vs. 1A, p < 0.001), and 0.90 ± 0.15 mm for method 1C (vs. 1A, p < 0.001). In the clinical study, method 2C was selected for DBS surgery in group II since it had the smallest registration error among the four methods tested. The registration error was 0.62 ± 0.22 mm (mean ± SD) for group I and 0.27 ± 0.07 mm for group II (p < 0.001). Postoperative electrode vector error was 0.97 ± 0.31 mm for group I and 0.65 ± 0.23 mm for group II (p < 0.001). There was a positive correlation between registration error and electrode vector error in both groups (group I: r = 0.69, p < 0.001; group II: r = 0.71, p < 0.001). The mean IESL was 5.0 ± 0.9 mm in group I and 5.8 ± 0.7 mm in group II (p < 0.001). The mean DBS power-on voltage was 1.63 ± 0.44 V in group I and 1.48 ± 0.38 V in group II (p = 0.027). In the UPDRS score, group I showed 50% ± 16% improvement and group II showed 52% ± 18% improvement (p = 0.724); there was no statistically significant difference in improvement on the UPDRS.

CONCLUSIONS

In DBS surgery assisted by the ROSA system, registration error and electrode vector error showed a positive correlation. The modified registration method could reduce the registration error and electrode vector error, but the long-term effects need to be further observed and evaluated.

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Shyamal C. Bir, Devi Prasad Patra, Tanmoy K. Maiti, Hai Sun, Bharat Guthikonda, Christina Notarianni and Anil Nanda

OBJECTIVE

Adult-onset hydrocephalus is not commonly discussed in the literature, especially regarding its demographic distribution. In contrast to pediatric hydrocephalus, which is related to a primary CSF pathway defect, its development in adults is often secondary to other pathologies. In this study, the authors investigated the epidemiology of adult-onset hydrocephalus as it pertains to different etiologies and in reference to age, sex, and race distributions.

METHODS

The authors retrospectively reviewed the clinical notes of 2001 patients with adult-onset hydrocephalus who presented to Louisiana State University Health Sciences Center within a 25-year span. Significant differences between the groups were analyzed by a chi-square test; p < 0.05 was considered significant.

RESULTS

The overall mean (± SEM) incidence of adult hydrocephalus in this population was 77 ± 30 per year, with a significant increase in incidence in the past decade (55 ± 3 [1990–2003] vs 102 ± 6 [2004–2015]; p < 0.0001). Hydrocephalus in a majority of the patients had a vascular etiology (45.5%) or was a result of a tumor (30.2%). The incidence of hydrocephalus in different age groups varied according to various pathologies. The incidence was significantly higher in males with normal-pressure hydrocephalus (p = 0.03) or head injury (p = 0.01) and higher in females with pseudotumor cerebri (p < 0.0001). In addition, the overall incidence of hydrocephalus was significantly higher in Caucasian patients (p = 0.0002) than in those of any other race.

CONCLUSIONS

Knowledge of the demographic variations in adult-onset hydrocephalus is helpful in achieving better risk stratification and better managing the disease in patients. For general applicability, these results should be validated in a large-scale meta-analysis based on a national population database.

Free access

Devi Prasad Patra, Shyamal C. Bir, Tanmoy K. Maiti, Piyush Kalakoti, Hugo Cuellar, Bharat Guthikonda, Hai Sun, Christina Notarianni and Anil Nanda

OBJECTIVE

Despite significant advances in the medical field and shunt technology, shunt malfunction remains a nightmare of pediatric neurosurgeons. In this setting, the ability to preoperatively predict the probability of shunt malfunction is quite compelling. The authors have compared the preoperative radiological findings in obstructive hydrocephalus and the subsequent clinical course of the patient to determine any association with overall shunt outcome.

METHODS

This retrospective study included all pediatric patients (age < 18 years) who had undergone ventriculoperitoneal shunt insertion for obstructive hydrocephalus. Linear measurements were taken from pre- and postoperative CT or MRI studies to calculate different indices and ratios including Evans' index, frontal horn index (FHI), occipital horn index (OHI), frontooccipital horn ratio (FOHR), and frontooccipital horn index ratio (FOIR). Other morphological features such as bi- or triventriculomegaly, right-left ventricular symmetry, and periventricular lucency (PVL) were also noted. The primary clinical outcomes that were reviewed included the need for shunt revision, time interval to first shunt revision, frequency of shunt revisions, and revision-free survival.

RESULTS

A total of 121 patients were eligible for the analysis. Nearly half of the patients (47.9%) required shunt revision. The presence of PVL was associated with lower revision rates than those in others (39.4% vs 58.2%, p = 0.03). None of the preoperative radiological indices or ratios showed any correlation with shunt revision. Nearly half of the patients with shunt revision required early revision (< 90 days of primary surgery). The reduction in the FOHR was high in patients who required early shunt revision (20.16% in patients with early shunt revision vs 6.4% in patients with late shunt revision, p = 0.009). Nearly half of the patients (48.3%) requiring shunt revision ultimately needed more than one revision procedure. Greater occipital horn dilation on preoperative images was associated with a lower frequency of shunt revision, as dictated by a high OHI and a low FOIR in patients with a single shunt revision as compared with those in patients who required multiple shunt revisions (p = 0.029 and 0.009, respectively). The mean follow-up was 49.9 months. Age was a significant factor affecting shunt revision–free survival. Patients younger than 6 months of age had significantly less revision-free survival than the patients older than 6 months (median survival of 10.1 vs 94.1 months, p = 0.004).

CONCLUSIONS

Preoperative radiological linear indices and ratios do not predict the likelihood of subsequent shunt malfunction. However, patients who required early shunt revision tended to have greater reductions in ventricular volumes on postoperative images. Therefore a greater reduction in ventricular volume is not actually desirable, and a ventricular volume high enough to reduce intracranial pressure is instead to be aimed at for long-term shunt compliance.

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Shyamal C. Bir, Anil Nanda, Hugo Cuellar, Hai Sun, Bharat Guthikonda, Cesar Liendo, Alireza Minagar and Oleg Y. Chernyshev

OBJECTIVE

Obstructive sleep apnea (OSA) is associated with the progression of abdominal and thoracic aortic aneurysms. However, the role of OSA in the overall outcome of intracranial aneurysms (IAs) has not yet been established. Authors of this report investigated the role of OSA in the overall outcome of IAs.

METHODS

Radiological and clinical data on patients (from 2010 through 2015) with confirmed IA were retrospectively reviewed. Significant differences between the OSA and non-OSA groups were determined using a chi-square test. Logistic regression analysis was performed to identify the predictors of an unfavorable IA outcome.

RESULTS

Among the 283 patients with confirmed IAs, 45 patients (16%) were positively screened for OSA, a proportion that was significantly higher than the prevalence of OSA in nonaneurysmal neurosurgical patients (4%, p = 0.008). The percentage of patients with hypertension (p = 0.018), a body mass index ≥ 30 kg/m2 (p < 0.0001), hyperlipidemia (p = 0.034), diabetes mellitus (p = 0.005), chronic heart disease (CHD; p = 0.024), or prior stroke (p = 0.03) was significantly higher in the OSA group than in the non-OSA group. Similarly, the percentage of wide-necked aneurysms (p = 0.00001) and patients with a poor Hunt and Hess Grade IV–V (p = 0.01) was significantly higher in the OSA group than in the non-OSA group. In addition, the percentage of ruptured aneurysms (p = 0.03) and vasospasms (p = 0.03) was significantly higher in the OSA group. The percentage of patients with poor modified Rankin Scale (mRS) scores (3–6) was significantly higher in the OSA group (p = 0.03). A separate cohort of patients with ruptured IAs showed similar results. In both univariate (p = 0.01) and multivariate (p = 0.04) regression analyses, OSA was identified as an individual predictor of an unfavorable outcome. In addition, hypertension and prior stroke were revealed as predictors of a poor IA outcome.

CONCLUSIONS

Complications of IA such as rupture and vasospasm are often the consequence of uncontrolled OSA. Overall outcome (mRS) of IAs is also affected by the co-occurrence of OSA. Therefore, the coexistence of OSA with IA affects the outcome of IAs. Obstructive sleep apnea is a risk factor for a poor outcome in IA patients.

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Sam Safavi-Abbasi, Hai Sun, Mark E. Oppenlander, Peter Nakaji, M. Yashar S. Kalani, Joseph M. Zabramski and Robert F. Spetzler

Intraoperative rupture of an intracranial aneurysm is a potentially devastating but controllable complication. The authors have successfully used the previously described cotton-clip technique to repair tears at the necks of aneurysms.1–4 A tear on the neck of the aneurysm is covered with a piece of cotton and held in place with a suction device. The cotton is then clipped onto the tear with an aneurysm clip, using the cotton as a bolster. This simple, effective method has been useful in repairing a partial avulsion of the neck of an aneurysm.1,3

The video can be found here: http://youtu.be/nT86RYVQWpc.

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Yu Shuang Tian, Di Zhong, Qing Qing Liu, Xiu Li Zhao, Hong Xue Sun, Jing Jin, Hai Ning Wang and Guo Zhong Li

OBJECTIVE

Ischemic stroke remains a significant cause of death and disability in industrialized nations. Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) of the JAK2/STAT3 pathway play important roles in the downstream signal pathway regulation of ischemic stroke–related inflammatory neuronal damage. Recently, microRNAs (miRNAs) have emerged as major regulators in cerebral ischemic injury; therefore, the authors aimed to investigate the underlying molecular mechanism between miRNAs and ischemic stroke, which may provide potential therapeutic targets for ischemic stroke.

METHODS

The JAK2- and JAK3-related miRNA (miR-135, miR-216a, and miR-433) expression levels were detected by real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot analysis in both oxygen-glucose deprivation (OGD)–treated primary cultured neuronal cells and mouse brain with middle cerebral artery occlusion (MCAO)–induced ischemic stroke. The miR-135, miR-216a, and miR-433 were determined by bioinformatics analysis that may target JAK2, and miR-216a was further confirmed by 3′ untranslated region (3′UTR) dual-luciferase assay. The study further detected cell apoptosis, the level of lactate dehydrogenase, and inflammatory mediators (inducible nitric oxide synthase [iNOS], matrix metalloproteinase–9 [MMP-9], tumor necrosis factor–α [TNF-α], and interleukin-1β [IL-1β]) after cells were transfected with miR-NC (miRNA negative control) or miR-216a mimics and subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) damage with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, annexin V–FITC/PI, Western blots, and enzyme-linked immunosorbent assay detection. Furthermore, neurological deficit detection and neurological behavior grading were performed to determine the infarction area and neurological deficits.

RESULTS

JAK2 showed its highest level while miR-216a showed its lowest level at day 1 after ischemic reperfusion. However, miR-135 and miR-433 had no obvious change during the process. The luciferase assay data further confirmed that miR-216a can directly target the 3′UTR of JAK2, and overexpression of miR-216a repressed JAK2 protein levels in OGD/R-treated neuronal cells as well as in the MCAO model ischemic region. In addition, overexpression of miR-216a mitigated cell apoptosis both in vitro and in vivo, which was consistent with the effect of knockdown of JAK2. Furthermore, the study found that miR-216a obviously inhibited the inflammatory mediators after OGD/R, including inflammatory enzymes (iNOS and MMP-9) and cytokines (TNF-α and IL-1β). Upregulating miR-216a levels reduced ischemic infarction and improved neurological deficit.

CONCLUSIONS

These findings suggest that upregulation of miR-216a, which targets JAK2, could induce neuroprotection against ischemic injury in vitro and in vivo, which provides a potential therapeutic target for ischemic stroke.

Full access

Hai-Ying Shen, Hai Sun, Marissa M. Hanthorn, Zhongwei Zhi, Jing-Quan Lan, David J. Poulsen, Ruikang K. Wang and Detlev Boison

Object

New experimental models and diagnostic methods are needed to better understand the pathophysiology of focal neocortical epilepsies in a search for improved epilepsy treatment options. The authors hypothesized that a focal disruption of adenosine homeostasis in the neocortex might be sufficient to trigger electrographic seizures. They further hypothesized that a focal disruption of adenosine homeostasis might affect microcirculation and thus offer a diagnostic opportunity for the detection of a seizure focus located in the neocortex.

Methods

Focal disruption of adenosine homeostasis was achieved by injecting an adeno-associated virus (AAV) engineered to overexpress adenosine kinase (ADK), the major metabolic clearance enzyme for the brain's endogenous anticonvulsant adenosine, into the neocortex of mice. Eight weeks following virus injection, the affected brain area was imaged via optical microangiography (OMAG) to detect changes in microcirculation. After completion of imaging, cortical electroencephalography (EEG) recordings were obtained from the imaged brain area.

Results

Viral expression of the Adk cDNA in astrocytes generated a focal area (~ 2 mm in diameter) of ADK overexpression within the neocortex. OMAG scanning revealed a reduction in vessel density within the affected brain area of approximately 23% and 29% compared with control animals and the contralateral hemisphere, respectively. EEG recordings revealed electrographic seizures within the focal area of ADK overexpression at a rate of 1.3 ± 0.2 seizures per hour (mean ± SEM).

Conclusions

The findings of this study suggest that focal adenosine deficiency is sufficient to generate a neocortical focus of hyperexcitability, which is also characterized by reduced vessel density. The authors conclude that their model constitutes a useful tool to study neocortical epilepsies and that OMAG constitutes a noninvasive diagnostic tool for the imaging of seizure foci with disrupted adenosine homeostasis.

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Sam Safavi-Abbasi, Noritaka Komune, Jacob B. Archer, Hai Sun, Nicholas Theodore, Jeffrey James, Andrew S. Little, Peter Nakaji, Michael E. Sughrue, Albert L. Rhoton and Robert F. Spetzler

OBJECT

The objective of this study was to describe the surgical anatomy and technical nuances of various vascularized tissue flaps.

METHODS

The surgical anatomy of various tissue flaps and their vascular pedicles was studied in 5 colored silicone-injected anatomical specimens. Medical records were reviewed of 11 consecutive patients who underwent repair of extensive skull base defects with a combination of various vascularized flaps.

RESULTS

The supraorbital, supratrochlear, superficial temporal, greater auricular, and occipital arteries contribute to the vascular supply of the pericranium. The pericranial flap can be designed based on an axial blood supply. Laterally, various flaps are supplied by the deep or superficial temporal arteries. The nasoseptal flap is a vascular pedicled flap based on the nasoseptal artery. Patients with extensive skull base defects can undergo effective repair with dual flaps or triple flaps using these pedicled vascularized flaps.

CONCLUSIONS

Multiple pedicled flaps are available for reconstitution of the skull base. Knowledge of the surgical anatomy of these flaps is crucial for the skull base surgeon. These vascularized tissue flaps can be used effectively as single or combination flaps. Multilayered closure of cranial base defects with vascularized tissue can be used safely and may lead to excellent repair outcomes.

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Evgenii Belykh, Ting Lei, Sam Safavi-Abbasi, Kaan Yagmurlu, Rami O. Almefty, Hai Sun, Kaith K. Almefty, Olga Belykh, Vadim A. Byvaltsev, Robert F. Spetzler, Peter Nakaji and Mark C. Preul

OBJECTIVE

Microvascular anastomosis is a basic neurosurgical technique that should be mastered in the laboratory. Human and bovine placentas have been proposed as convenient surgical practice models; however, the histologic characteristics of these tissues have not been compared with human cerebral vessels, and the models have not been validated as simulation training models. In this study, the authors assessed the construct, face, and content validities of microvascular bypass simulation models that used human and bovine placental vessels.

METHODS

The characteristics of vessel segments from 30 human and 10 bovine placentas were assessed anatomically and histologically. Microvascular bypasses were performed on the placenta models according to a delineated training module by “trained” participants (10 practicing neurosurgeons and 7 residents with microsurgical experience) and “untrained” participants (10 medical students and 3 residents without experience). Anastomosis performance and impressions of the model were assessed using the Northwestern Objective Microanastomosis Assessment Tool (NOMAT) scale and a posttraining survey.

RESULTS

Human placental arteries were found to approximate the M2–M4 cerebral and superficial temporal arteries, and bovine placental veins were found to approximate the internal carotid and radial arteries. The mean NOMAT performance score was 37.2 ± 7.0 in the untrained group versus 62.7 ± 6.1 in the trained group (p < 0.01; construct validity). A 50% probability of allocation to either group corresponded to 50 NOMAT points. In the posttraining survey, 16 of 17 of the trained participants (94%) scored the model's replication of real bypass surgery as high, and 16 of 17 (94%) scored the difficulty as “the same” (face validity). All participants, 30 of 30 (100%), answered positively to questions regarding the ability of the model to improve microsurgical technique (content validity).

CONCLUSIONS

Human placental arteries and bovine placental veins are convenient, anatomically relevant, and beneficial models for microneurosurgical training. Microanastomosis simulation using these models has high face, content, and construct validities. A NOMAT score of more than 50 indicated successful performance of the microanastomosis tasks.