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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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Bharath Raju, Fareed Jumah, Omar Ashraf, Vinayak Narayan, Gaurav Gupta, Hai Sun, Patrick Hilden, and Anil Nanda

Big data has transformed into a trend phrase in healthcare and neurosurgery, becoming a pervasive and inescapable phrase in everyday life. The upsurge in big data applications is a direct consequence of the drastic boom in information technology as well as the growing number of internet-connected devices called the Internet of Things in healthcare. Compared with business, marketing, and other sectors, healthcare applications are lagging due to a lack of technical knowledge among healthcare workers, technological limitations in acquiring and analyzing the data, and improper governance of healthcare big data. Despite these limitations, the medical literature is flooded with big data–related articles, and most of these are filled with abstruse terminologies such as machine learning, artificial intelligence, artificial neural network, and algorithm. Many of the recent articles are restricted to neurosurgical registries, creating a false impression that big data is synonymous with registries. Others advocate that the utilization of big data will be the panacea to all healthcare problems and research in the future. Without a proper understanding of these principles, it becomes easy to get lost without the ability to differentiate hype from reality. To that end, the authors give a brief narrative of big data analysis in neurosurgery and review its applications, limitations, and the challenges it presents for neurosurgeons and healthcare professionals naive to this field. Awareness of these basic concepts will allow neurosurgeons to understand the literature regarding big data, enabling them to make better decisions and deliver personalized care.

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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.

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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.

Free access

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. 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.,

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

Free access

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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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, Felix Moron, Hai Sun, Mark E. Oppenlander, M. Yashar S. Kalani, Celene B. Mulholland, Joseph M. Zabramski, Peter Nakaji, and Robert F. Spetzler

OBJECTIVE

To address the challenges of microsurgically treating broad-based, frail, and otherwise complex aneurysms that are not amenable to direct clipping, alternative techniques have been developed. One such technique is to use cotton to augment clipping (“cotton-clipping” technique), which is also used to manage intraoperative aneurysm neck rupture, and another is to reinforce unclippable segments or remnants of aneurysm necks with cotton (“cotton-augmentation” technique). This study reviews the natural history of patients with aneurysms treated with cotton-clipping and cotton-augmentation techniques.

METHODS

The authors queried a database consisting of all patients with aneurysms treated at Barrow Neurological Institute in Phoenix, Arizona, between January 1, 2004, and December 31, 2014, to identify cases in which cotton-clipping or cotton-augmentation strategies had been used. Management was categorized as the cotton-clipping technique if cotton was used within the blades of the aneurysm clip and as the cotton-clipping technique if cotton was used to reinforce aneurysms or portions of the aneurysm that were unclippable due to the presence of perforators, atherosclerosis, or residual aneurysms. Data were reviewed to assess patient outcomes and annual rates of aneurysm recurrence or hemorrhage after the initial procedures were performed.

RESULTS

The authors identified 60 aneurysms treated with these techniques in 57 patients (18 patients with ruptured aneurysms and 39 patients with unruptured aneurysms) whose mean age was 53.1 years (median 55 years; range 24–72 years). Twenty-three aneurysms (11 cases of subarachnoid hemorrhage) were treated using cotton-clipping and 37 with cotton-augmentation techniques (7 cases of subarachnoid hemorrhage). In total, 18 patients presented with subarachnoid hemorrhage. The mean Glasgow Outcome Scale (GOS) score at the time of discharge was 4.4. At a mean follow-up of 60.9 ± 35.6 months (median 70 months; range 10–126 months), the mean GOS score at last follow-up was 4.8. The total number of patient follow-up years was 289.4. During the follow-up period, none of the cotton-clipped aneurysms increased in size, changed in configuration, or rebled. None of the patients experienced early rebleeding. The annual hemorrhage rate for aneurysms treated with cotton-augmentation was 0.52% and the recurrence rate was 1.03% per year. For all patients in the study, the overall risk of hemorrhage was 0.35% per year and the annual recurrence rate was 0.69%.

CONCLUSIONS

Cotton-clipping is an effective and durable treatment strategy for intraoperative aneurysm rupture and for management of broad-based aneurysms. Cotton-augmentation can be safely used to manage unclippable or partially clipped intracranial aneurysms and affords protection from early aneurysm re-rupture and a relatively low rate of late rehemorrhage.