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Takero Hirata, Manabu Kinoshita, Keisuke Tamari, Yuji Seo, Osamu Suzuki, Nobuhide Wakai, Takamune Achiha, Toru Umehara, Hideyuki Arita, Naoki Kagawa, Yonehiro Kanemura, Eku Shimosegawa, Naoya Hashimoto, Jun Hatazawa, Haruhiko Kishima, Teruki Teshima and Kazuhiko Ogawa

OBJECTIVE

It is important to correctly and precisely define the target volume for radiotherapy (RT) of malignant glioma. 11C-methionine (MET) positron emission tomography (PET) holds promise for detecting areas of glioma cell infiltration: the authors’ previous research showed that the magnitude of disruption of MET and 18F-fluorodeoxyglucose (FDG) uptake correlation (decoupling score [DS]) precisely reflects glioma cell invasion. The purpose of the present study was to analyze volumetric and geometrical properties of RT target delineation based on DS and compare them with those based on MRI.

METHODS

Twenty-five patients with a diagnosis of malignant glioma were included in this study. Three target volumes were compared: 1) contrast-enhancing core lesions identified by contrast-enhanced T1-weighted images (T1Gd), 2) high-intensity lesions on T2-weighted images, and 3) lesions showing high DS (DS ≥ 3; hDS). The geometrical differences of these target volumes were assessed by calculating the probabilities of overlap and one encompassing the other. The correlation of geometrical features of RT planning and recurrence patterns was further analyzed.

RESULTS

The analysis revealed that T1Gd with a 2.0-cm margin was able to cover the entire high DS area only in 6 (24%) patients, which indicates that microscopic invasion of glioma cells often extended more than 2.0 cm beyond a Gd-enhanced core lesion. Insufficient coverage of high DS regions with RT target volumes was suggested to be a risk for out-of-field recurrence. Higher coverage of hDS by T1Gd with a 2-cm margin (i.e., higher values of “[T1Gd + 2 cm]/hDS”) had a trend to positively impact overall and progression-free survival. Cox regression analysis demonstrated that low coverage of hDS by T1Gd with a 2-cm margin was predictive of disease recurrence outside the Gd-enhanced core lesion, indicative of out-of-field reoccurrence.

CONCLUSIONS

The findings of this study indicate that MRI is inadequate for target delineation for RT in malignant glioma treatment. Expanding the treated margins substantially beyond the MRI-based target volume may reduce the risk of undertreatment, but it may also result in unnecessary irradiation of uninvolved regions. As MET/FDG PET-DS seems to provide more accurate information for target delineation than MRI in malignant glioma treatment, this method should be further evaluated on a larger scale.

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Maria Peris-Celda, Laura Salgado-Lopez, Carrie Y. Inwards, Aditya Raghunathan, Carrie M. Carr, Jeffrey R. Janus, Janalee K. Stokken and Jamie J. Van Gompel

Benign notochordal cell tumors (BNCTs) are considered to be benign intraosseous lesions of notochord origin; however, recent spine studies have suggested the possibility that some chordomas arise from BNCTs. Here, the authors describe two cases demonstrating histological features of BNCT and concomitant chordoma involving the clivus, which, to the best of the authors’ knowledge, have not been previously documented at this anatomical site.

An 18-year-old female presented with an incidentally discovered clival mass. Magnetic resonance imaging revealed a 2.8-cm nonenhancing lesion in the upper clivus that was T2 hyperintense and T1 hypointense. She underwent an uneventful endoscopic transsphenoidal resection. Histologically, the tumor demonstrated areas of classic chordoma and a distinct intraosseous BNCT component. The patient completed adjuvant radiation therapy. Follow-up showed no recurrence at 18 months.

A 39-year-old male presented with an incidentally discovered 2.8-cm clival lesion. The nonenhancing mass was T2 hyperintense and T1 hypointense. Surgical removal of the lesion was performed through an endoscopic transsphenoidal approach. Histological analysis revealed areas of BNCT with typical features of chordoma. Follow-up did not demonstrate recurrence at 4 years.

These cases document histologically concomitant BNCT and chordoma involving the clivus, suggesting that the BNCT component may be a precursor of chordoma.

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Mladen Djurasovic, Jeffrey L. Gum, Charles H. Crawford III, Kirk Owens II, Morgan Brown, Portia Steele, Steven D. Glassman and Leah Y. Carreon

OBJECTIVE

The midline transforaminal lumbar interbody fusion (MIDLIF) using cortical screw fixation is a novel, minimally invasive procedure that may offer enhanced recovery over traditional open transforaminal lumbar interbody fusion (TLIF). Little information is available regarding the comparative cost-effectiveness of the MIDLIF over conventional TLIF. The purpose of this study was to compare cost-effectiveness of minimally invasive MIDLIF with open TLIF.

METHODS

From a prospective, multisurgeon, surgical database, a consecutive series of patients undergoing 1- or 2-level MIDLIF for degenerative lumbar conditions was identified and propensity matched to patients undergoing TLIF based on age, sex, smoking status, BMI, diagnosis, American Society of Anesthesiologists Physical Status Classification System (ASA) class, and levels fused. Direct costs at 1 year were collected, including costs associated with the index surgical visit as well as costs associated with readmission. Improvement in health-related quality of life was measured using EQ-5D and SF-6D.

RESULTS

Of 214 and 181 patients undergoing MIDLIF and TLIF, respectively, 33 cases in each cohort were successfully propensity matched. Consistent with propensity matching, there was no difference in age, sex, BMI, diagnosis, ASA class, smoking status, or levels fused. Spondylolisthesis was the most common indication for surgery in both cohorts. Variable direct costs at 1 year were $2493 lower in the MIDLIF group than in the open TLIF group (mean $15,867 vs $17,612, p = 0.073). There was no difference in implant (p = 0.193) or biologics (p = 0.145) cost, but blood utilization (p = 0.015), operating room supplies (p < 0.001), hospital room and board (p < 0.001), pharmacy (p = 0.010), laboratory (p = 0.004), and physical therapy (p = 0.009) costs were all significantly lower in the MIDLIF group. Additionally, the mean length of stay was decreased for MIDLIF as well (3.21 vs 4.02 days, p = 0.05). The EQ-5D gain at 1 year was 0.156 for MIDLIF and 0.141 for open TLIF (p = 0.821). The SF-6D gain at 1 year was 0.071 for MIDLIF and 0.057 for open TLIF (p = 0.551).

CONCLUSIONS

Compared with patients undergoing traditional open TLIF, those undergoing MIDLIF have similar 1-year gains in health-related quality of life, with total direct costs that are $2493 lower. Although the findings were not statistically significant, minimally invasive MIDLIF showed improved cost-effectiveness at 1 year compared with open TLIF.

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Nardin Samuel and Mitchel Berger

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Bob S. Carter and Fred G. Barker II

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Toru Doi, Hideki Nakamoto, Koji Nakajima, Shima Hirai, Yusuke Sato, So Kato, Yuki Taniguchi, Yoshitaka Matsubayashi, Ko Matsudaira, Katsushi Takeshita, Sakae Tanaka and Yasushi Oshima

OBJECTIVE

Preoperative mood disorders such as depression and anxiety are known to be associated with poor health-related quality of life (HRQOL) outcomes after lumbar spine surgery. However, the effects of preoperative depression and anxiety on postoperative HRQOL outcomes and patient satisfaction in cervical compressive myelopathy are yet to be clarified. This study aimed to investigate the effect of depression and anxiety on HRQOL outcomes and patient satisfaction following surgery for cervical compressive myelopathy.

METHODS

The authors reviewed the cases of all consecutive patients with cervical compressive myelopathy who had undergone surgical treatment in the period between January 2012 and March 2017 at their institution. Using the Hospital Anxiety and Depression Scale (HADS), the authors classified patients as depressed (HADS-D+) or not depressed (HADS-D−) and anxious (HADS-A+) or not anxious (HADS-A−). Patient HRQOL was evaluated preoperatively and at the end of at least 1 year after surgery using the physical and mental component summaries of the SF-12 Health Survey, EQ-5D (EuroQol health survey of five dimensions), Neck Disability Index, and Japanese Orthopaedic Association scale. Patient satisfaction was evaluated on the basis of a seven-item questionnaire and divided into two categories: satisfied and dissatisfied. Preoperative HRQOL statuses, postoperative improvements in HRQOL outcomes, and patient satisfaction were compared between the groups.

RESULTS

Among the 121 patients eligible for inclusion in the study, there were 69 patients (57.0%) without depression (HADS-D−) and 52 (43.0%) with depression (HADS-D+) and 82 patients (67.8%) without anxiety (HADS-A−) and 39 (32.2%) with anxiety (HADS-A+). All patients who completed both the preoperative and postoperative questionnaires had significant postoperative improvements in all HRQOL outcomes. The HADS-D+ and HADS-A+ patients had poorer preoperative HRQOL statuses than the HADS-D− and HADS-A− patients, respectively. However, statistically significant improvements in all HRQOL outcomes were observed in both HADS-D+ and HADS-A+ patients. Patient satisfaction was comparable between the HADS-D or HADS-A groups.

CONCLUSIONS

Cervical compressive myelopathy patients with preoperative depression or anxiety according to the HADS tool had worse preoperative HRQOL statuses. However, patients with cervical compressive myelopathy showed significant improvements in HRQOL outcomes and had sufficient levels of satisfaction after surgery regardless of the presence of preoperative depression or anxiety.

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Michael Karsy, Jian Guan, Ilyas Eli, Andrea A. Brock, Sarah T. Menacho and Min S. Park

OBJECTIVE

Hypovitaminosis D is prevalent in neurocritical care patients, but the potential to improve patient outcome by replenishing vitamin D has not been investigated. This single-center, double-blinded, placebo-controlled, randomized (1:1) clinical trial was designed to assess the effect on patient outcome of vitamin D supplementation in neurocritical care patients with hypovitaminosis D.

METHODS

From October 2016 until April 2018, emergently admitted neurocritical care patients with vitamin D deficiency (≤ 20 ng/ml) were randomized to receive vitamin D3 (cholecalciferol, 540,000 IU) (n = 134) or placebo (n = 133). Hospital length of stay (LOS) was the primary outcome; secondary outcomes included intensive care unit (ICU) LOS, repeat vitamin D levels, patient complications, and patient disposition. Exploratory analysis evaluated specific subgroups of patients by LOS, Glasgow Coma Scale (GCS) score, and Simplified Acute Physiology Score (SAPS II).

RESULTS

Two-hundred seventy-four patients were randomized (intent-to-treat) and 267 were administered treatment within 48 hours of admission (as-treated; 61.2% of planned recruitment) and monitored. The mean age of as-treated patients was 54.0 ± 17.2 years (56.9% male, 77.2% white). After interim analysis suggested a low conditional power for outcome difference (predictive power 0.12), the trial was halted. For as-treated patients, no significant difference in hospital LOS (10.4 ± 14.5 days vs 9.1 ± 7.9 days, p = 0.4; mean difference 1.3, 95% CI −1.5 to 4.1) or ICU LOS (5.8 ± 7.5 days vs 5.4 ± 6.4 days, p = 0.4; mean difference 0.4, 95% CI −1.3 to 2.1) was seen between vitamin D3 and placebo groups, respectively. Vitamin D3 supplementation significantly improved repeat serum levels compared with placebo (20.8 ± 9.3 ng/ml vs 12.8 ± 4.8 ng/ml, p < 0.001) without adverse side effects. No subgroups were identified by exclusion of LOS outliers or segregation by GCS score, SAPS II, or severe vitamin D deficiency (≤ 10 ng/ml).

CONCLUSIONS

Despite studies showing that vitamin D can predict prognosis, supplementation in vitamin D–deficient neurocritical care patients did not result in appreciable improvement in outcomes and likely does not play a role in acute clinical recovery.

Clinical trial registration no.: NCT02881957 (clinicaltrials.gov)

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Nobutaka Horie, Shuntaro Sato, Makio Kaminogo, Yoichi Morofuji, Tsuyoshi Izumo, Takeo Anda and Takayuki Matsuo

OBJECTIVE

Aneurysm rebleeding is a major cause of death and morbidity in patients with aneurysmal subarachnoid hemorrhage (SAH). Recognizing the predictors of rebleeding might help to identify patients who will benefit from acute management. This study was performed to investigate the predictors of aneurysm rebleeding and their impact on clinical outcomes in the preoperative, intraoperative, and postoperative periods.

METHODS

The incidence of rebleeding, demographic data, and clinical data from 4933 patients with aneurysmal SAH beginning in the year 2000 were retrospectively analyzed in the Nagasaki SAH Registry Study. The authors performed multiple logistic regression analyses to identify the risk factors contributing to rebleeding and outcome after SAH.

RESULTS

Preoperative rebleeding occurred in 7.2% of patients. Patient age (p = 0.01), multiple aneurysms (p < 0.01), aneurysm size (p < 0.0001), and heart disease (p = 0.03) were significantly associated with preoperative rebleeding. Conversely, intraoperative rebleeding occurred in 11.2% of patients. Aneurysm location (anterior communicating artery [ACoA]), family history (p = 0.02), preoperative rebleeding (p < 0.01), and clipping/coiling (p < 0.0001) were significantly associated with intraoperative rebleeding. Interaction analysis showed that clipping significantly affected intraoperative rebleeding at the ACoA (OR 4.00; 95% CI 1.82–8.80; p < 0.001). Postoperative rebleeding occurred in 2.4% of patients. Coiling/clipping (p < 0.0001) and intraoperative rebleeding (p < 0.01) were significantly associated with postoperative rebleeding. Rebleeding in all time periods examined significantly contributed to the clinical outcome after SAH.

CONCLUSIONS

Aneurysm rebleeding after SAH has specific characteristics in the preoperative, intraoperative, and postoperative periods, and all of these characteristics contribute to the clinical outcome. The ACoA has a higher risk of intraoperative rebleeding, and endovascular coiling could be a good candidate in terms of techniques for preventing intraoperative rebleeding, although complete aneurysm obliteration should be accomplished.

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Wouter I. Schievink, M. Marcel Maya, Franklin G. Moser, Ravi S. Prasad, Rachelle B. Cruz, Miriam Nuño and Richard I. Farb

OBJECTIVE

Spontaneous spinal CSF–venous fistulas are a distinct type of spinal CSF leak recently described in patients with spontaneous intracranial hypotension (SIH). Using digital subtraction myelography (DSM) with the patient in the prone position, the authors have been able to demonstrate such fistulas in about one-fifth of patients with SIH in whom conventional spinal imaging (MRI or CT myelography) showed no evidence for a CSF leak (i.e., the presence of extradural CSF). The authors compared findings of DSM with patients in the lateral decubitus position versus the prone position and now report a significantly increased yield of identifying spinal CSF–venous fistulas with this modification of their imaging protocol.

METHODS

The population consisted of 23 patients with SIH who underwent DSM in the lateral decubitus position and 26 patients with SIH who underwent DSM in the prone position. None of the patients had evidence of a CSF leak on conventional spinal imaging.

RESULTS

A CSF–venous fistula was demonstrated in 17 (74%) of the 23 patients who underwent DSM in the lateral decubitus position compared to 4 (15%) of the 26 patients who underwent DSM in the prone position (p < 0.0001). The mean age of these 16 women and 5 men was 52.5 years (range 36–66 years).

CONCLUSIONS

Among SIH patients in whom conventional spinal imaging showed no evidence of a CSF leak, DSM in the lateral decubitus position demonstrated a CSF–venous fistula in about three-fourths of patients compared to only 15% of patients when the DSM was performed in the prone position, an approximately five-fold increase in the detection rate. Spinal CSF–venous fistulas are not rare among patients with SIH.