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Caroline Gewiss, Christian Hagel and Kara Krajewski

OBJECTIVE

To shed light on the role of relaxin in cerebral cavernous malformations (CCMs) in adults and children, the authors investigated endothelial cell (EC) expression of relaxin 1, 2, and 3; vascular endothelial growth factor receptor–1 and –2 (VEGFR-1 and -2); Ki-67; vascular geometry; and hemorrhage, as well as the clinical presentation of 32 patients with surgically resected lesions.

METHODS

Paraffin-embedded sections of 32 CCMs and 5 normal nonvascular lesion control (NVLC) brain tissue samples were immunohistochemically stained with antibodies to relaxin 1, 2, and 3; angiogenesis growth factor receptors Flt-1 (VEGFR-1) and Flk-1 (VEGFR-2); and proliferation marker Ki-67. For morphometric analysis, Elastica van Gieson stain was used, and for hemorrhage demonstration, Turnbull stain was used. Data from the pediatric and adult CCMs were compared with each other and with those obtained from the NVLCs. Statistical analyses were performed with Fisher’s exact test, the chi-square test, the phi correlation coefficient, and the Student t-test. A p value < 0.05 was considered significant.

RESULTS

Pediatric and adult cavernoma vessels did not significantly differ in diameter. Hemorrhage was observed in CCMs but not in NVLC samples (p < 0.05). There was no difference in expression of Ki-67, VEGFR-1 and -2, and relaxin 1, 2, and 3 in the ECs of pediatric and adult CCMs. The ECs of CCMs were largely negative for relaxin 3 compared to NVLCs (p < 0.05), whereas CCMs, compared to control brain tissue samples, more frequently expressed Flt-1 and relaxin 2 (p < 0.05). Ki-67 was not expressed in the NVLCs, but the difference was not statistically significant. Relaxin 1 and 2 expression and increased expression of VEGFR-1 were associated with a supra- versus infratentorial location (p < 0.05).

CONCLUSIONS

Relaxin 1 and 2 and VEGFR-1 play a role in supratentorial cavernomas. Relaxin 3 may play a physiological role in normal brain vasculature. Relaxin 1 and 3 are also found in normal cerebral vasculature. Relaxin 1, 2, and 3 are associated with increased VEGFR-1 expression.

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Hiroki Ushirozako, Go Yoshida, Tomohiko Hasegawa, Yu Yamato, Tatsuya Yasuda, Tomohiro Banno, Hideyuki Arima, Shin Oe, Tomohiro Yamada, Koichiro Ide, Yuh Watanabe, Tadayoshi Kurita and Yukihiro Matsuyama

OBJECTIVE

Transcranial motor evoked potential (TcMEP) monitoring may be valuable for predicting postoperative neurological complications with a high sensitivity and specificity, but one of the most frequent problems is the high false-positive rate. The purpose of this study was to clarify the differences in the risk factors for false-positive TcMEP alerts seen when performing surgery in patients with pediatric scoliosis and adult spinal deformity and to identify a method to reduce the false-positive rate.

METHODS

The authors retrospectively analyzed 393 patients (282 adult and 111 pediatric patients) who underwent TcMEP monitoring while under total intravenous anesthesia during spinal deformity surgery. They defined their cutoff (alert) point as a final TcMEP amplitude of ≤ 30% of the baseline amplitude. Patients with false-positive alerts were classified into one of two groups: a group with pediatric scoliosis and a group with adult spinal deformity.

RESULTS

There were 14 cases of false-positive alerts (13%) during pediatric scoliosis surgery and 62 cases of false-positive alerts (22%) during adult spinal deformity surgery. Compared to the true-negative cases during adult spinal deformity surgery, the false-positive cases had a significantly longer duration of surgery and greater estimated blood loss (both p < 0.001). Compared to the true-negative cases during pediatric scoliosis surgery, the false-positive cases had received a significantly higher total fentanyl dose and a higher mean propofol dose (0.75 ± 0.32 mg vs 0.51 ± 0.18 mg [p = 0.014] and 5.6 ± 0.8 mg/kg/hr vs 5.0 ± 0.7 mg/kg/hr [p = 0.009], respectively). A multivariate logistic regression analysis revealed that the duration of surgery (1-hour difference: OR 1.701; 95% CI 1.364–2.120; p < 0.001) was independently associated with false-positive alerts during adult spinal deformity surgery. A multivariate logistic regression analysis revealed that the mean propofol dose (1-mg/kg/hr difference: OR 3.117; 95% CI 1.196–8.123; p = 0.020), the total fentanyl dose (0.05-mg difference; OR 1.270; 95% CI 1.078–1.497; p = 0.004), and the duration of surgery (1-hour difference: OR 2.685; 95% CI 1.131–6.377; p = 0.025) were independently associated with false-positive alerts during pediatric scoliosis surgery.

CONCLUSIONS

Longer duration of surgery and greater blood loss are more likely to result in false-positive alerts during adult spinal deformity surgery. In particular, anesthetic doses were associated with false-positive TcMEP alerts during pediatric scoliosis surgery. The authors believe that false-positive alerts during pediatric scoliosis surgery, in particular, are caused by “anesthetic fade.”

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Anne E. Carolus, Jens Möller, Martin R. Hofmann, Johannes A. P. van de Nes, Hubert Welp, Kirsten Schmieder and Christopher Brenke

OBJECTIVE

Optical coherence tomography (OCT) is an imaging technique that uses the light-backscattering properties of different tissue types to generate an image. In an earlier feasibility study the authors showed that it can be applied to visualize human peripheral nerves. As a follow-up, this paper focuses on the interpretation of the images obtained.

METHODS

Ten different short peripheral nerve specimens were retained following surgery. In a first step they were examined by OCT during, or directly after, surgery. In a second step the nerve specimens were subjected to histological examination. Various steps of image processing were applied to the OCT raw data acquired. The improved OCT images were compared with the sections stained by H & E. The authors assigned the structures in the images to the various nerve components including perineurium, fascicles, and intrafascicular microstructures.

RESULTS

The results show that OCT is able to resolve the myelinated axons. A weighted averaging filter helps in identifying the borders of structural features and reduces artifacts at the same time. Tissue-remodeling processes due to injury (perineural fibrosis or neuroma) led to more homogeneous light backscattering. Anterograde axonal degeneration due to sharp injury led to a loss of visible axons and to an increase of light-backscattering tissue as well. However, the depth of light penetration is too small to allow generation of a complete picture of the nerve.

CONCLUSIONS

OCT is the first in vivo imaging technique that is able to resolve a nerve’s structures down to the level of myelinated axons. It can yield information about focal and segmental pathologies.

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Shaohui He, Chen Ye, Nanzhe Zhong, Minglei Yang, Xinghai Yang and Jianru Xiao

OBJECTIVE

The surgical treatment of an upper cervical spinal tumor (UCST) at C1–2/C1–3 is challenging due to anterior exposure and reconstruction. Limited information has been published concerning the effective approach and reconstruction for an anterior procedure after C1–2/C1–3 UCST resection. The authors attempted to introduce a novel, customized, anterior craniocervical reconstruction between the occipital condyles and inferior vertebrae through a modified high-cervical retropharyngeal approach (mHCRA) in addressing C1–2/C1–3 spinal tumors.

METHODS

Seven consecutive patients underwent 2-stage UCST resection with circumferential reconstruction. Posterior decompression and occiput-cervical instrumentation was conducted at the stage 1 operation, and anterior craniocervical reconstruction using a 3D-printed implant was performed between the occipital condyles and inferior vertebrae via an mHCRA. The clinical characteristics, perioperative complications, and radiological outcomes were reviewed, and the rationale for anterior craniocervical reconstruction was also clarified.

RESULTS

The mean age of the 7 patients in the study was 47.6 ± 19.0 years (range 12–72 years) when referred to the authors’ center. Six patients (85.7%) had recurrent tumor status, and the interval from primary to recurrence status was 53.0 ± 33.7 months (range 24–105 months). Four patients (57.1%) were diagnosed with a spinal tumor involving C1–3, and 3 patients (42.9%) with a C1–2 tumor. For the anterior procedure, the mean surgical duration and average blood loss were 4.1 ± 0.9 hours (range 3.0–6.0 hours) and 558.3 ± 400.5 ml (range 100–1300 ml), respectively. No severe perioperative complications occurred, except 1 patient with transient dysphagia. The mean pre- and postoperative visual analog scale scores were 8.0 ± 0.8 (range 7–9) and 2.4 ± 0.5 (range 2.0–3.0; p < 0.001), respectively, and the mean improvement rate of cervical spinal cord function was 54.7% ± 13.8% (range 42.9%–83.3%) based on the modified Japanese Orthopaedic Association scale score (p < 0.001). Circumferential instrumentation was in good position and no evidence of disease was found at the mean follow-up of 14.8 months (range 7.3–24.2 months).

CONCLUSIONS

The mHCRA provides optimal access to the surgical field at the C0–3 level. Customized anterior craniocervical fixation between the occipital condyles and inferior vertebrae can be feasible and effective in managing anterior reconstruction after UCST resection.

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Christopher J. Stapleton, Animesh Acharjee, Hannah J. Irvine, Zoe C. Wolcott, Aman B. Patel and W. Taylor Kimberly

OBJECTIVE

Metabolite profiling (or metabolomics) can identify candidate biomarkers for disease and potentially uncover new pathways for intervention. The goal of this study was to identify potential biomarkers of functional outcome after subarachnoid hemorrhage (SAH).

METHODS

The authors performed high-throughput metabolite profiling across a broad spectrum of chemical classes (163 metabolites) on plasma samples taken from 191 patients with SAH who presented to Massachusetts General Hospital between May 2011 and October 2016. Samples were drawn at 3 time points following ictus: 0–5, 6–10, and 11–14 days. Elastic net (EN) and LASSO (least absolute shrinkage and selection operator) machine learning analyses were performed to identify metabolites associated with 90-day functional outcomes as assessed by the modified Rankin Scale (mRS). Additional univariate and multivariate analyses were then conducted to further examine the relationship between metabolites and clinical variables and 90-day functional outcomes.

RESULTS

One hundred thirty-seven (71.7%) patients with aneurysmal SAH met the criteria for inclusion. A good functional outcome (mRS score 0–2) at 90 days was found in 79 (57.7%) patients. Patients with good outcomes were younger (p = 0.002), had lower admission Hunt and Hess grades (p < 0.0001) and modified Fisher grades (p < 0.0001), and did not develop hydrocephalus (p < 0.0001) or delayed cerebral ischemia (DCI) (p = 0.049). EN and LASSO machine learning methods identified taurine as the leading metabolite associated with 90-day functional outcome (p < 0.0001). Plasma concentrations of the amino acid taurine from samples collected between days 0 and 5 after aneurysmal SAH were 21.9% (p = 0.002) higher in patients with good versus poor outcomes. Logistic regression demonstrated that taurine remained a significant predictor of functional outcome (p = 0.013; OR 3.41, 95% CI 1.28–11.4), after adjusting for age, Hunt and Hess grade, modified Fisher grade, hydrocephalus, and DCI.

CONCLUSIONS

Elevated plasma taurine levels following aneurysmal SAH predict a good 90-day functional outcome. While experimental evidence in animals suggests that this effect may be mediated through downregulation of pro-inflammatory cytokines, additional studies are required to validate this hypothesis in humans.

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Robert C. Rennert, Martin P. Powers, Jeffrey A. Steinberg, Takanori Fukushima, John D. Day, Alexander A. Khalessi and Michael L. Levy

OBJECTIVE

The far-lateral and extreme-lateral infrajugular transcondylar–transtubercular exposure (ELITE) and extreme-lateral transcondylar transodontoid (ELTO) approaches provide access to lesions of the foramen magnum, inferolateral to mid-clivus, and ventral pons and medulla. A subset of pathologies in this region require manipulation of the vertebral artery (VA)–dural interface. Although a cuff of dura is commonly left on the VA to avoid vessel injury during these approaches, there are varying descriptions of the degree of VA-dural separation that is safely achievable. In this paper the authors provide a detailed histological analysis of the VA-dural junction to guide microsurgical technique for posterolateral skull base approaches.

METHODS

An ELITE approach was performed on 6 preserved adult cadaveric specimens. The VA-dural entry site was resected, processed for histological analysis, and qualitatively assessed by a neuropathologist.

RESULTS

Histological analysis demonstrated a clear delineation between the intima and media of the VA in all specimens. No clear plane was identified between the connective tissue of the dura and the connective tissue of the VA adventitia.

CONCLUSIONS

The VA forms a contiguous plane with the connective tissue of the dura at its dural entry site. When performing posterolateral skull base approaches requiring manipulation of the VA-dural interface, maintenance of a dural cuff on the VA is critical to minimize the risk of vascular injury.

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Katie P. Fehnel, Craig D. McClain and Edward R. Smith

There are no practice guidelines for the treatment of moyamoya disease in pregnant women. The need for such guidelines, however, is evidenced by the numerous case reports, case series, and systematic reviews in the literature highlighting an at-risk period for female moyamoya patients of childbearing age. Here the authors review and interpret the existing literature as it applies to their index patient and expand the literature in support of treating select patients during pregnancy. The authors describe what is to their knowledge the first case reported in the literature of a patient successfully treated with indirect surgical revascularization during the first trimester, who went on to deliver a healthy term baby without complications.

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Se-Jun Park, Keun-Ho Lee, Chong-Suh Lee, Joon Young Jung, Jin Ho Park, Gab-Lae Kim and Ki-Tack Kim

OBJECTIVE

The goal of this study was to evaluate the radiographic and clinical results of instrumentation surgery without fusion for metastases to the spine.

METHODS

Between 2010 and 2017, patients with spinal tumors who underwent instrumentation without fusion surgery were consecutively evaluated. Preoperative and postoperative clinical data were evaluated. Data were inclusive for last follow-up and just prior to death if the patient died. Instrumentation-related complications included screw migration, screw or rod breakage, cage migration, and screw loosening.

RESULTS

Excluding patients who died within 6 months, a total of 136 patients (140 operations) were recruited. The average follow-up duration was 16.5 months (median 12.4 months). The pain visual analog scale score decreased from 6.4 to 2.5 (p < 0.001) and the Eastern Cooperative Oncology Group scale score improved (p < 0.001). There were only 3 cases (2.1%) of symptomatic instrumentation-related complications that resulted in revisions. There were 6 cases of nonsymptomatic complications. The most common complication was screw migration or pull-out (5 cases). There were 3 cases of screw or rod breakage and 1 case of cage migration. Two-thirds of the cases of instrumentation-related complications occurred after 6 months, with a mean postoperative period of 1 year.

CONCLUSIONS

The current study reported successful outcomes with very low complication rates after nonfusion surgery for patients with spinal metastases, even among those who survived for more than 6 months. More than half of the instrumentation-related complications were asymptomatic and did not require revision. The results suggest that nonfusion surgery might be sufficient for a majority of patients with spinal metastases.

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Tushar Garg and Apurva Shrigiriwar