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Hormuzdiyar H. Dasenbrock, Robert F. Rudy, Timothy R. Smith, William B. Gormley, Nirav J. Patel, Kai U. Frerichs, M. Ali Aziz-Sultan and Rose Du

OBJECTIVE

The complex decision analysis of unruptured intracranial aneurysms entails weighing the benefits of aneurysm repair against operative risk. The goal of the present analysis was to build and validate a predictive scale that identifies patients with the greatest odds of a postsurgical adverse event.

METHODS

Data on patients who underwent surgical clipping of an unruptured aneurysm were extracted from the prospective National Surgical Quality Improvement Program registry (NSQIP; 2007–2014); NSQIP does not systematically collect data on patients undergoing intracranial endovascular intervention. Multivariable logistic regression evaluated predictors of any 30-day adverse event; variables screened included patient demographics, comorbidities, functional status, preoperative laboratory values, aneurysm location/complexity, and operative time. A predictive scale was constructed based on statistically significant independent predictors, which was validated using both NSQIP (2015–2016) and the Nationwide Inpatient Sample (NIS; 2002–2011).

RESULTS

The NSQIP unruptured aneurysm scale was proposed: 1 point was assigned for a bleeding disorder; 2 points for age 51–60 years, cardiac disease, diabetes mellitus, morbid obesity, anemia (hematocrit < 36%), operative time 240–330 minutes; 3 points for leukocytosis (white blood cell count > 12,000/μL) and operative time > 330 minutes; and 4 points for age > 60 years. An increased score was predictive of postoperative stroke or coma (NSQIP: p = 0.002, C-statistic = 0.70; NIS: p < 0.001, C-statistic = 0.61), a medical complication (NSQIP: p = 0.01, C-statistic = 0.71; NIS: p < 0.001, C-statistic = 0.64), and a nonroutine discharge (NSQIP: p < 0.001, C-statistic = 0.75; NIS: p < 0.001, C-statistic = 0.66) in both validation populations. Greater score was also predictive of increased odds of any adverse event, a major complication, and an extended hospitalization in both validation populations (p ≤ 0.03).

CONCLUSIONS

The NSQIP unruptured aneurysm scale may augment the risk stratification of patients undergoing microsurgical clipping of unruptured cerebral aneurysms.

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Nico Sollmann, Alessia Fratini, Haosu Zhang, Claus Zimmer, Bernhard Meyer and Sandro M. Krieg

OBJECTIVE

Navigated transcranial magnetic stimulation (nTMS) in combination with diffusion tensor imaging fiber tracking (DTI FT) is increasingly used to locate subcortical language-related pathways. The aim of this study was to establish nTMS-based DTI FT for preoperative risk stratification by evaluating associations between lesion-to-tract distances (LTDs) and aphasia and by determining a cut-off LTD value to prevent surgery-related permanent aphasia.

METHODS

Fifty patients with left-hemispheric, language-eloquent brain tumors underwent preoperative nTMS language mapping and nTMS-based DTI FT, followed by tumor resection. nTMS-based DTI FT was performed with a predefined fractional anisotropy (FA) of 0.10, 0.15, 50% of the individual FA threshold (FAT), and 75% FAT (minimum fiber length [FL]: 100 mm). The arcuate fascicle (AF), superior longitudinal fascicle (SLF), inferior longitudinal fascicle (ILF), uncinate fascicle (UC), and frontooccipital fascicle (FoF) were identified in nTMS-based tractography, and minimum LTDs were measured between the lesion and the AF and between the lesion and the closest other subcortical language-related pathway (SLF, ILF, UC, or FoF). LTDs were then associated with the level of aphasia (no/transient or permanent surgery-related aphasia, according to follow-up examinations).

RESULTS

A significant difference in LTDs was observed between patients with no or only surgery-related transient impairment and those who developed surgery-related permanent aphasia with regard to the AF (FA = 0.10, p = 0.0321; FA = 0.15, p = 0.0143; FA = 50% FAT, p = 0.0106) as well as the closest other subcortical language-related pathway (FA = 0.10, p = 0.0182; FA = 0.15, p = 0.0200; FA = 50% FAT, p = 0.0077). Patients with surgery-related permanent aphasia showed the lowest LTDs in relation to these tracts. Thus, LTDs of ≥ 8 mm (AF) and ≥ 11 mm (SLF, ILF, UC, or FoF) were determined as cut-off values for surgery-related permanent aphasia.

CONCLUSIONS

nTMS-based DTI FT of subcortical language-related pathways seems suitable for risk stratification and prediction in patients suffering from language-eloquent brain tumors. Thus, the current role of nTMS-based DTI FT might be expanded, going beyond the level of being a mere tool for surgical planning and resection guidance.

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Taiichi Saito, Yoshihiro Muragaki, Manabu Tamura, Takashi Maruyama, Masayuki Nitta, Shunsuke Tsuzuki, Satoko Fukuchi, Mana Ohashi and Takakazu Kawamata

OBJECTIVE

Resection of gliomas in the precentral gyrus carries a risk of severe motor dysfunction. To prevent permanent, severe postoperative motor dysfunction, reliable intraoperative predictors of postoperative function are required. Since 2005, the authors have removed gliomas in the precentral gyrus with combined functional mapping and estimation of intraoperative voluntary movement (IVM) during awake craniotomy and transcortical motor evoked potentials (MEPs). The purpose of the current study was to evaluate whether intraoperative findings of combined monitoring of IVM during awake craniotomy and transcortical MEP monitoring were useful for predicting postoperative motor function of patients with gliomas in the precentral gyrus.

METHODS

The current study included 30 patients who underwent resection of precentral gyrus gliomas during awake craniotomy from April 2000 to January 2018. All tumors were removed with monitoring of IVM during awake craniotomy and transcortical MEPs. Postoperative motor function was classified as stable or declined, with the extent of decline categorized as mild, moderate, or severe. We defined moderate and severe deficits were those that hindered daily life.

RESULTS

In 28 of 30 cases, available waveforms were obtained with transcortical MEPs. The mean extent of resection (EOR) was 93%. Relative to preoperative status, motor function 6 months after surgery was considered stable in 20 patients and was considered to show mild decline in 7, moderate decline in 2, and severe decline in 1. Motor function 6 months after surgery was significantly correlated with IVM (p = 0.0096), changes in transcortical MEPs (decline ≤ or > 50%) (p = 0.0163), EOR, and ischemic lesions on postoperative MRI. Six patients with no change in IVM showed stable motor function 6 months after surgery. Only 2 patients with a decline in IVM and a decline in MEPs ≤ 50% had a decline in motor function 6 months after surgery (18%; 2/11 patients), whereas 11 patients with a decline in IVM and a decline in MEPs > 50% had such a decline in motor function (73%; 8/11 patients) including 2 patients with moderate and 1 with severe deficits. Three patients with moderate or severe motor deficits showed the lowest MEP values (< 100 µV).

CONCLUSIONS

Combined judgment from monitoring of IVM during awake craniotomy and transcortical MEPs is useful for predicting postoperative motor function during removal of gliomas in the precentral gyrus. Maximum resection was achieved with an acceptable morbidity rate. Thus, these tumors should not be considered unresectable.

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Ricarda Lechner, David Putzer, Martin Krismer, Christian Haid, Alois Obwegeser and Martin Thaler

OBJECTIVE

The positive effect of primary lumbar disc surgery on braking reaction time (BRT) has already been shown. The authors investigated the effect of recurrent lumbar disc herniation surgery on BRT.

METHODS

Twenty-four patients (mean age 49.9 years) were investigated for BRT 1 day before surgery, postoperatively before hospital discharge, and 4 to 5 weeks after surgery. Thirty-one healthy subjects served as a control group.

RESULTS

Significant improvement of BRT following surgery was found in all patients (p < 0.05). For patients with right-sided recurrent disc herniation, median BRT was 736 msec before surgery, 685 msec immediately postoperatively, and 662 msec at follow-up. For patients with left-sided recurrent disc herniation, median BRT was 674 msec preoperatively, 585 msec postoperatively, and 578 msec at follow-up. Control subjects had a median BRT of 487, which differed significantly from the patient BRTs at all 3 test times (p < 0.05).

CONCLUSIONS

A significant reduction in BRT in patients with recurrent disc herniation was found following lumbar disc revision surgery, indicating a positive impact of surgery. Due to the improvement in BRT observed immediately after surgery, we conclude that it is appropriate to recommend that patients keep driving after being discharged from the hospital.

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Tomoaki Suzuki, Christopher J. Stapleton, Matthew J. Koch, Kazutoshi Tanaka, Soichiro Fujimura, Takashi Suzuki, Takeshi Yanagisawa, Makoto Yamamoto, Yukihiko Fujii, Yuichi Murayama and Aman B. Patel

OBJECTIVE

Degenerative cerebral aneurysm walls are associated with aneurysm rupture and subarachnoid hemorrhage. Thin-walled regions (TWRs) represent fragile areas that may eventually lead to aneurysm rupture. Previous computational fluid dynamics (CFD) studies reported the correlation of maximum pressure (Pmax) areas and TWRs; however, the correlation with aneurysm rupture has not been established. This study aims to investigate this hemodynamic correlation.

METHODS

The aneurysmal wall surface at the Pmax areas was intraoperatively evaluated using a fluid flow formula under pulsatile blood flow conditions in 23 patients with 23 saccular middle cerebral artery (MCA) bifurcation aneurysms (16 unruptured and 7 ruptured). The pressure difference (Pd) at the Pmax areas was calculated by subtracting the average pressure (Pave) from the Pmax and normalized by dividing this by the dynamic pressure at the aneurysm inlet side. The wall shear stress (WSS) was also calculated at the Pmax areas, aneurysm dome, and parent artery. These hemodynamic parameters were used to validate the correlation with TWRs in unruptured MCA aneurysms. The characteristic hemodynamic parameters at the rupture points in ruptured MCA aneurysms were then determined.

RESULTS

In 13 of 16 unruptured aneurysms (81.2%), Pmax areas were identified that corresponded to TWRs. In 5 of the 7 ruptured cerebral aneurysms, the Pmax areas coincided with the rupture point. At these areas, the Pd values were not higher than those of the TWRs in unruptured cerebral aneurysms; however, minimum WSS, time-averaged WSS, and normalized WSS at the rupture point were significantly lower than those of the TWRs in unruptured aneurysms (p < 0.01).

CONCLUSIONS

At the Pmax area of TWRs, decreased WSS appears to be the crucial hemodynamic parameter that indicates the risk of aneurysm rupture.

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Zhuo-jie Liu, Bang-ping Qian, Yong Qiu, Sai-hu Mao, Jun Jiang and Bin Wang

OBJECTIVE

Relocation of the apex is often found in patients with ankylosing spondylitis (AS)–associated thoracolumbar/lumbar kyphosis after corrective surgery. This study evaluates the influence of different postoperative apex locations on surgical and clinical outcomes of osteotomy for patients with AS and thoracolumbar kyphosis.

METHODS

Sixty-two patients with a mean age of 34.6 ± 9.7 years (range 17–59 years) and a minimum of 2 years of follow-up, who underwent 1-level lumbar pedicle subtraction osteotomy for AS-related thoracolumbar kyphosis, were enrolled in the study, as well as 62 age-matched healthy individuals. Patients were divided into 2 groups according to the postoperative location of the apex (group 1, T8 or above; group 2, T9 or below). Demographic data, radiographic measurements (including 3 postoperative apex-related parameters), and clinical outcomes were compared between the 2 groups preoperatively, postoperatively, and at the last follow-up. Furthermore, a subgroup analysis was performed among patients with a postoperative apex located at T6–11 and postoperatively the entire AS cohort was compared with normal controls regarding the apex location of the thoracic spine.

RESULTS

In the majority of the enrolled patients, the apex location changed from T12–L2 preoperatively to T6–9 postoperatively. The sagittal vertical axis (SVA) differed significantly both postoperatively (25.7 vs 59.0 mm, p = 0.001) and at the last follow-up (34.6 vs 59.9 mm, p = 0.003) between the 2 groups, and the patients in group 1 had significantly smaller horizontal distance between the C7-vertical line and the apex (DCA) than the patients in group 2 (67.5 vs 103.7 mm, p = 0.001). Subgroup analysis demonstrated similar results, showing that the patients with a postoperative apex located at T8 or above had an average SVA < 47 mm. Notably, a significant correlation was found between postoperative SVA and DCA (r = 0.642, p = 0.001). Patients who underwent an osteotomy at L3 had limited apex relocation but larger SVA correction than those at L1 or L2. However, no significant difference was found in health-related quality of life between the 2 groups.

CONCLUSIONS

AS patients with an apex located at T8 or above after surgery tended to have better SVA correction (within 47 mm) than those who had a more caudally located apical vertebra. For ideal postoperative apex relocation, a higher (closer to or at the preoperative apex) level of osteotomy is more likely to obtain the surgical goal.

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Weijun Wang, Steve Swenson, Hee-Yeon Cho, Florence M. Hofman, Axel H. Schönthal and Thomas C. Chen

OBJECTIVE

Many pharmaceutical agents are highly potent but are unable to exert therapeutic activity against disorders of the central nervous system (CNS), because the blood-brain barrier (BBB) impedes their brain entry. One such agent is bortezomib (BZM), a proteasome inhibitor that is approved for the treatment of multiple myeloma. Preclinical studies established that BZM can be effective against glioblastoma (GBM), but only when the drug is delivered via catheter directly into the brain lesion, not after intravenous systemic delivery. The authors therefore explored alternative options of BZM delivery to the brain that would avoid invasive procedures and minimize systemic exposure.

METHODS

Using mouse and rat GBM models, the authors applied intranasal drug delivery, where they co-administered BZM together with NEO100, a highly purified, GMP-manufactured version of perillyl alcohol that is used in clinical trials for intranasal therapy of GBM patients.

RESULTS

The authors found that intranasal delivery of BZM combined with NEO100 significantly prolonged survival of tumor-bearing animals over those that received vehicle alone and also over those that received BZM alone or NEO100 alone. Moreover, BZM concentrations in the brain were higher after intranasal co-delivery with NEO100 as compared to delivery in the absence of NEO100.

CONCLUSIONS

This study demonstrates that intranasal delivery with a NEO100-based formulation enables noninvasive, therapeutically effective brain delivery of a pharmaceutical agent that otherwise does not efficiently cross the BBB.

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Chetna Tailor, W. Spencer Ashby, Donald R. Gorassini, Stephen P. Lownie, Kimberley Walsh, David Pelz and Robert R. Hammond

OBJECTIVE

Endovascular approaches have evolved from a technique practiced at very few centers to a widely available option in the management of arteriovenous malformations (AVMs) of the central nervous system. Embolization can be employed as definitive therapy or as an adjunct to surgical excision. A wide variety of embolic agents have been successfully developed and used in the clinical setting. In addition to facilitating vascular occlusion, embolic agents induce a number of reactive and destructive changes in vessel walls and the surrounding tissue. However, studies examining the pathological changes induced by different embolic agents and varying times of exposure are scarce. The goal of the present study was to compare embolic agents and time of exposure on the pathology in excised specimens.

METHODS

The records of the Department of Pathology at the London Health Sciences Centre were searched for embolized AVMs for the 35-year period 1980–2015. All cases were reevaluated for clinical and technical variables and standardized histopathological findings. Cases were grouped by embolic agent, volume of agent used, and time to excision.

RESULTS

A total of 101 specimens were identified. Embolic agents were invariably associated with a range of pathological findings, some of which may affect the integrity of vessel walls or the reestablishment of flow, thrombosis, acute and chronic inflammatory changes, angionecrosis, extravasation, and recanalization. The type of embolic agent did not predict differences in the incidence or severity of histopathological changes. Larger volumes of embolic agent were associated with a greater proportion of vessels containing embolic material. AVMs excised early (< 1 week postembolization) contained more acute vasculitis, while those excised later (≥ 1 week postembolization) were more likely to exhibit recanalization and foreign body giant cell infiltrates.

CONCLUSIONS

Embolic agents induce a predictable range and temporal progression of pathological changes in cerebral AVMs. The embolic agents studied are indistinguishable in terms of the range and frequency of pathological reactions induced. Greater volumes of embolic agent are associated with more abundant agent within the lesion, but the proportion of vessels and vascular cross-sectional areas containing agent is small. Several changes are significantly associated with time postembolization. Acute vasculitis is a more common finding in the 1st week, while recanalization and foreign body–type granulomatous inflammation are more common at 1 week and beyond.

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You Gyoung Yi, Keewon Kim, Hyung-Ik Shin, Moon Suk Bang, Hee-Soo Kim, Jinwoo Choi, Kyu-Chang Wang, Seung-Ki Kim, Ji Yeoun Lee, Ji Hoon Phi and Han Gil Seo

OBJECTIVE

This study aimed to investigate the feasibility and safety of intraoperative motor evoked potential (MEP) monitoring in infants less than 3 months of age.

METHODS

The authors investigated 25 cases in which infants younger than 3 months (mean age 72.8 days, range 39–87) underwent neurosurgery between 2014 and 2017. Myogenic MEPs were obtained through transcranial electrical stimulation. In all cases, surgery was performed under total intravenous anesthesia, maintained with remifentanil and propofol.

RESULTS

MEPs were documented in 24 infants, the sole exception being 1 infant who was lethargic and had 4-limb weakness before surgery. The mean stimulation intensity maintained during monitoring was 596 ± 154 V (range 290–900 V). In 19 of 24 infants MEP signals remained at ≥ 50% of the baseline amplitude throughout the operation. Among 5 cases with a decrease in intraoperative MEP amplitude, the MEP signal was recovered in one during surgery, and in the other case a neurological examination could not be performed after surgery. In the other 3 cases, 2 infants had relevant postoperative weakness and the other did not show postoperative neurological deficits. Postoperative weakness was not observed in any of the 20 infants who had no deterioration (n = 19) or only temporary deterioration (n = 1) in MEP signal during surgery.

CONCLUSIONS

Transcranial electrical MEPs could be implemented during neurosurgery in infants between 1 and 3 months of age. Intraoperative MEP monitoring may be a safe adjunct for neurosurgical procedures in these very young patients.

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Robert M. Starke, David J. McCarthy, Ching-Jen Chen, Hideyuki Kano, Brendan J. McShane, John Lee, Mohana Rao Patibandla, David Mathieu, Lucas T. Vasas, Anthony M. Kaufmann, Wei Gang Wang, Inga S. Grills, Christopher P. Cifarelli, Gabriella Paisan, John Vargo, Tomas Chytka, Ladislava Janouskova, Caleb E. Feliciano, Nanthiya Sujijantarat, Charles Matouk, Veronica Chiang, Judith Hess, Rafael Rodriguez-Mercado, Daniel A. Tonetti, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

The authors performed a study to evaluate the hemorrhagic rates of cerebral dural arteriovenous fistulas (dAVFs) and the risk factors of hemorrhage following Gamma Knife radiosurgery (GKRS).

METHODS

Data from a cohort of patients undergoing GKRS for cerebral dAVFs were compiled from the International Radiosurgery Research Foundation. The annual posttreatment hemorrhage rate was calculated as the number of hemorrhages divided by the patient-years at risk. Risk factors for dAVF hemorrhage prior to GKRS and during the latency period after radiosurgery were evaluated in a multivariate analysis.

RESULTS

A total of 147 patients with dAVFs were treated with GKRS. Thirty-six patients (24.5%) presented with hemorrhage. dAVFs that had any cortical venous drainage (CVD) (OR = 3.8, p = 0.003) or convexity or torcula location (OR = 3.3, p = 0.017) were more likely to present with hemorrhage in multivariate analysis. Half of the patients had prior treatment (49.7%). Post-GRKS hemorrhage occurred in 4 patients, with an overall annual risk of 0.84% during the latency period. The annual risks of post-GKRS hemorrhage for Borden type 2–3 dAVFs and Borden type 2–3 hemorrhagic dAVFs were 1.45% and 0.93%, respectively. No hemorrhage occurred after radiological confirmation of obliteration. Independent predictors of hemorrhage following GKRS included nonhemorrhagic neural deficit presentation (HR = 21.6, p = 0.027) and increasing number of past endovascular treatments (HR = 1.81, p = 0.036).

CONCLUSIONS

Patients have similar rates of hemorrhage before and after radiosurgery until obliteration is achieved. dAVFs that have any CVD or are located in the convexity or torcula were more likely to present with hemorrhage. Patients presenting with nonhemorrhagic neural deficits and a history of endovascular treatments had higher risks of post-GKRS hemorrhage.