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Karim Mithani, Ying Meng, David Pinilla, Nova Thani, Kayee Tung, Richard Leung and Howard J. Ginsberg

A 52-year-old man with a 10-year history of treatment-resistant asthma presented with repeated exacerbations over the course of 10 months. His symptoms were not responsive to salbutamol or inhaled corticosteroid agents, and he developed avascular necrosis of his left hip as a result of prolonged steroid therapy. Physical examination and radiography revealed signs consistent with diffuse idiopathic skeletal hyperostosis (DISH), including a C7–T1 osteophyte causing severe tracheal compression. The patient underwent C6–T1 anterior discectomy and fusion, and the compressive osteophyte was removed, which completely resolved his “asthma.” Postoperative pulmonary function tests showed normalization of his FEV1/FVC ratio, and there was no airway reactivity on methacholine challenge. DISH is a systemic, noninflammatory condition characterized by ossification of spinal entheses, and it can present with respiratory disturbances due to airway compression by anterior cervical osteophytes. The authors present, to the best of their knowledge, the first documented case of asthma as a presentation of DISH.

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Eric Suero Molina, Christian Ewelt, Nils Warneke, Michael Schwake, Michael Müther, Stephanie Schipmann and Walter Stummer

OBJECTIVE

Recent efforts to improve visualization of 5-aminolevulinic acid (5-ALA)–induced protoporphyrin IX (PPIX) fluorescence resulted in a dual-labeling technique, combining it with fluorescein sodium in a prototype setup. Fluorescein identifies regions with blood-brain barrier breakdown in gliomas. However, normally perfused and edematous brain fluoresces unselectively, with strong background enhancement. The aim of this study was to test the feasibility of a novel, integrated filter combination using porphyrins for selective tumor identification and fluorescein for background enhancement.

METHODS

A microscope with a novel built-in filter system (YB 475) for visualizing both fluorescein and 5-ALA–induced porphyrins was used. Resection limits were identified with the conventional BLUE 400 filter system. Six patients harboring contrast ring-enhancing lesions were analyzed.

RESULTS

The complete surgical field could now be illuminated. Fluorescein was helpful for improving background visualization, and enhancing dura, edematous tissue, and cortex. Overlapping regions with both fluorophores harbored merged orange fluorescence. PPIX fluorescence was better visualized, even in areas beyond a normal working distance of approximately 25 cm, where the BLUE 400 filters recognized no or weak fluorescence.

CONCLUSIONS

The novel filter system improved general tissue brightness and background visualization, enhancing fluorescence-guided tumor resection. Furthermore, it appears promising from a scientific perspective, enabling the simultaneous and direct observation of areas with blood-brain barrier breakdown and PPIX fluorescence.

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Santiago Cepeda, Ana María Castaño-León, Pablo M. Munarriz, Igor Paredes, Irene Panero, Carla Eiriz, Pedro A. Gómez and Alfonso Lagares

OBJECTIVE

Traumatic intracerebral hemorrhage (TICH) represents approximately 13%–48% of the lesions after a traumatic brain injury (TBI), and hemorrhagic progression (HP) occurs in 38%–63% of cases. In previous studies, decompressive craniectomy (DC) has been characterized as a risk factor in the HP of TICH; however, few studies have focused exclusively on this relationship. The object of the present study was to analyze the relationship between DC and the growth of TICH and to reveal any correlation with the size of the craniectomy, degree of cerebral parenchymal herniation (CPH), or volumetric expansion of the TICH.

METHODS

The authors retrospectively analyzed the records of 497 adult patients who had been consecutively admitted after suffering a severe or moderate closed TBI. An inclusion criterion was presentation with one or more TICHs on the initial or control CT. Demographic, clinical, radiological, and treatment variables were assessed for associations.

RESULTS

Two hundred three patients presenting with 401 individual TICHs met the selection criteria. TICH growth was observed in 281 cases (70.1%). Eighty-two cases (20.4%) underwent craniectomy without TICH evacuation. In the craniectomy group, HP was observed in 71 cases (86.6%); in the noncraniectomy group (319 cases), HP occurred in 210 cases (65.8%). The difference in the incidence of HP between the two groups was statistically significant (OR 3.41, p < 0.01). The mean area of the craniectomy was 104.94 ± 27.5 cm2, and the mean CPH distance through the craniectomy was 17.85 ± 11.1 mm. The mean increase in the TICH volume was greater in the groups with a craniectomy area > 115 cm2 and CPH > 25 mm (16.12 and 14.47 cm3, respectively, p = 0.01 and 0.02). After calculating the propensity score (PS), the authors followed three statistical methods—matching, stratification, and inverse probability treatment weighting (IPTW)—thereby obtaining an adequate balance of the covariates. A statistically significant relationship was found between HP and craniectomy (OR 2.77, p = 0.004). This correlation was confirmed with the three methodologies based on the PS with odds greater than 2.

CONCLUSIONS

DC is a risk factor for the growth of TICH, and there is also an association between the size of the DC and the magnitude of the volume increase in the TICH.

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Philip Cheng, Li Ma, Sonali Shaligram, Espen J. Walker, Shun-Tai Yang, Chaoliang Tang, Wan Zhu, Lei Zhan, Qiang Li, Xiaonan Zhu, Michael T. Lawton and Hua Su

OBJECTIVE

A high level of vascular endothelial growth factor (VEGF) has been implicated in brain arteriovenous malformation (bAVM) bleeding and rupture. However, direct evidence is missing. In this study the authors used a mouse bAVM model to test the hypothesis that elevation of focal VEGF levels in bAVMs exacerbates the severity of bAVM hemorrhage.

METHODS

Brain AVMs were induced in adult mice in which activin receptor–like kinase 1 (Alk1, a gene that causes AVM) gene exons 4–6 were floxed by intrabasal ganglia injection of an adenoviral vector expressing Cre recombinase to induce Alk1 mutation and an adeno-associated viral vector expressing human VEGF (AAV-VEGF) to induce angiogenesis. Two doses of AAV-VEGF (5 × 109 [high] or 2 × 109 [low]) viral genomes were used. In addition, the common carotid artery and external jugular vein were anastomosed in a group of mice treated with low-dose AAV-VEGF 6 weeks after the model induction to induce cerebral venous hypertension (VH), because VH increases the VEGF level in the brain. Brain samples were collected 8 weeks after the model induction. Hemorrhages in the bAVM lesions were quantified on brain sections stained with Prussian blue, which detects iron deposition. VEGF levels were quantified in bAVM tissue by enzyme-linked immunosorbent assay.

RESULTS

Compared to mice injected with a low dose of AAV-VEGF, the mice injected with a high dose had higher levels of VEGF (p = 0.003) and larger Prussian blue–positive areas in the bAVM lesion at 8 or 9 weeks after model induction (p = 0.002). VH increased bAVM hemorrhage in the low-dose AAV-VEGF group. The overall mortality in the high-dose AAV-VEGF group was 26.7%, whereas no mouse died in the low-dose AAV-VEGF group without VH. In contrast, VH caused a mortality of 50% in the low-dose AAV-VEGF group.

CONCLUSIONS

Using mouse bAVM models, the authors provided direct evidence that elevation of the VEGF level increases bAVM hemorrhage and mouse mortality.

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Anne E. Carolus, Marcel Lenz, Martin Hofmann, Hubert Welp, Kirsten Schmieder and Christopher Brenke

OBJECTIVE

Because of their complex topography, long courses, and small diameters, peripheral nerves are challenging structures for radiological diagnostics. However, imaging techniques in the area of peripheral nerve diseases have undergone unexpected development in recent decades. They include MRI and high-resolution sonography (HRS). Yet none of those imaging techniques reaches a resolution comparable to that of histological sections. Fascicles are the smallest discernable structure. Optical coherence tomography (OCT) is the first imaging technique that is able to depict a nerve’s ultrastructure at micrometer resolution. In the current study, the authors present an in vivo assessment of human peripheral nerves using OCT.

METHODS

OCT measurement was performed in 34 patients with different peripheral nerve pathologies, i.e., nerve compression syndromes. The nerves were examined during surgery after their exposure. Only the sural nerve was twice examined ex vivo. The Thorlabs OCT systems Callisto and Ganymede were used. For intraoperative use, a hand probe was covered with a sterile foil. Different postprocessing imaging techniques were applied and evaluated. In order to highlight certain structures, five texture parameters based on gray-level co-occurrence matrices were calculated according to Haralick.

RESULTS

The intraoperative use of OCT is easy and intuitive. Image artifacts are mainly caused by motion and the sterile foil. If the artifacts are kept at a low level, the hyporeflecting bundles of nerve fascicles and their inner parts can be displayed. In the Haralick evaluation, the second angular moment is most suitable to depict the connective tissue.

CONCLUSIONS

OCT is a new imaging technique that has shown promise in peripheral nerve surgery for particular questions. Its resolution exceeds that provided by recent radiological possibilities such as MRI and HRS. Since its field of view is relatively small, faster acquisition times would be highly desirable and have already been demonstrated by other groups. Currently, the method resembles an optical biopsy and can be a supplement to intraoperative sonography, giving high-resolution insight into a suspect area that has been located by sonography in advance.

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Marissa D’Souza, Kevin S. Chen, Jarrett Rosenberg, W. Jeffrey Elias, Howard M. Eisenberg, Ryder Gwinn, Takaomi Taira, Jin Woo Chang, Nir Lipsman, Vibhor Krishna, Keiji Igase, Kazumichi Yamada, Haruhiko Kishima, Rees Cosgrove, Jordi Rumià, Michael G. Kaplitt, Hidehiro Hirabayashi, Dipankar Nandi, Jaimie M. Henderson, Kim Butts Pauly, Mor Dayan, Casey H. Halpern and Pejman Ghanouni

OBJECTIVE

Skull density ratio (SDR) assesses the transparency of the skull to ultrasound. Magnetic resonance–guided focused ultrasound (MRgFUS) thalamotomy in essential tremor (ET) patients with a lower SDR may be less effective, and the risk for complications may be increased. To address these questions, the authors analyzed clinical outcomes of MRgFUS thalamotomy based on SDRs.

METHODS

In 189 patients, 3 outcomes were correlated with SDRs. Efficacy was based on improvement in Clinical Rating Scale for Tremor (CRST) scores 1 year after MRgFUS. Procedural efficiency was determined by the ease of achieving a peak voxel temperature of 54°C. Safety was based on the rate of the most severe procedure-related adverse event. SDRs were categorized at thresholds of 0.45 and 0.40, selected based on published criteria.

RESULTS

Of 189 patients, 53 (28%) had an SDR < 0.45 and 20 (11%) had an SDR < 0.40. There was no significant difference in improvement in CRST scores between those with an SDR ≥ 0.45 (58% ± 24%), 0.40 ≤ SDR < 0.45 (i.e., SDR ≥ 0.40 but < 0.45) (63% ± 27%), and SDR < 0.40 (49% ± 28%; p = 0.0744). Target temperature was achieved more often in those with an SDR ≥ 0.45 (p < 0.001). Rates of adverse events were lower in the groups with an SDR < 0.45 (p = 0.013), with no severe adverse events in these groups.

CONCLUSIONS

MRgFUS treatment of ET can be effectively and safely performed in patients with an SDR < 0.45 and an SDR < 0.40, although the procedure is more efficient when SDR ≥ 0.45.

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Shyam S. Rao, David Y. Chung, Zoe Wolcott, Faheem Sheriff, Ayaz M. Khawaja, Hang Lee, Mary M. Guanci, Thabele M. Leslie-Mazwi, W. Taylor Kimberly, Aman B. Patel and Guy A. Rordorf

OBJECTIVE

There is variability and uncertainty about the optimal approach to the management and discontinuation of an external ventricular drain (EVD) after subarachnoid hemorrhage (SAH). Evidence from single-center randomized trials suggests that intermittent CSF drainage and rapid EVD weans are safe and associated with shorter ICU length of stay (LOS) and fewer EVD complications. However, a recent survey revealed that most neurocritical care units across the United States employ continuous CSF drainage with a gradual wean strategy. Therefore, the authors sought to determine the optimal EVD management approach at their institution.

METHODS

The authors reviewed records of 200 patients admitted to their institution from 2010 to 2016 with aneurysmal SAH requiring an EVD. In 2014, the neurocritical care unit of the authors’ institution revised the internal EVD management guidelines from a continuous CSF drainage with gradual wean approach (continuous/gradual) to an intermittent CSF drainage with rapid EVD wean approach (intermittent/rapid). The authors performed a retrospective multivariable analysis to compare outcomes before and after the guideline change.

RESULTS

The authors observed a significant reduction in ventriculoperitoneal (VP) shunt rates after changing to an intermittent CSF drainage with rapid EVD wean approach (13% intermittent/rapid vs 35% continuous/gradual, OR 0.21, p = 0.001). There was no increase in delayed VP shunt placement at 3 months (9.3% vs 8.6%, univariate p = 0.41). The intermittent/rapid EVD approach was also associated with a shorter mean EVD duration (10.2 vs 15.6 days, p < 0.001), shorter ICU LOS (14.2 vs 16.9 days, p = 0.001), shorter hospital LOS (18.2 vs 23.7 days, p < 0.0001), and lower incidence of a nonfunctioning EVD (15% vs 30%, OR 0.29, p = 0.006). The authors found no significant differences in the rates of symptomatic vasospasm (24.6% vs 20.2%, p = 0.52) or ventriculostomy-associated infections (1.3% vs 8.8%, OR 0.30, p = 0.315) between the 2 groups.

CONCLUSIONS

An intermittent CSF drainage with rapid EVD wean approach is associated with fewer VP shunt placements, fewer complications, and shorter LOS compared to a continuous CSF drainage with gradual EVD wean approach. There is a critical need for prospective multicenter studies to determine if the authors’ experience is generalizable to other centers.

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Toru Serizawa, Masaaki Yamamoto, Yoshinori Higuchi, Yasunori Sato, Takashi Shuto, Atsuya Akabane, Hidefumi Jokura, Shoji Yomo, Osamu Nagano, Jun Kawagishi and Kazuhiro Yamanaka

OBJECTIVE

The Japanese Leksell Gamma Knife (JLGK)0901 study proved the efficacy of Gamma Knife radiosurgery (GKRS) in patients with 5–10 brain metastases (BMs) as compared to those with 2–4, showing noninferiority in overall survival and other secondary endpoints. However, the difference in local tumor progression between patients with 2–4 and those with 5–10 BMs has not been sufficiently examined for this data set. Thus, the authors reappraised this issue, employing the updated JLGK0901 data set with detailed observation via enhanced MRI. They applied sophisticated statistical methods to analyze the data.

METHODS

This was a prospective observational study of 1194 patients harboring 1–10 BMs treated with GKRS alone. Patients were categorized into groups A (single BM, 455 cases), B (2–4 BMs, 531 cases), and C (5–10 BMs, 208 cases). Local tumor progression was defined as a 20% increase in the maximum diameter of the enhanced lesion as compared to its smallest documented maximum diameter on enhanced MRI. The authors compared cumulative incidence differences determined by competing risk analysis and also conducted propensity score matching.

RESULTS

Local tumor progression was observed in 212 patients (17.8% overall, groups A/B/C: 93/89/30 patients). Cumulative incidences of local tumor progression in groups A, B, and C were 15.2%, 10.6%, and 8.7% at 1 year after GKRS; 20.1%, 16.9%, and 13.5% at 3 years; and 21.4%, 17.4%, and not available at 5 years, respectively. There were no significant differences in local tumor progression between groups B and C. Local tumor progression was classified as tumor recurrence in 139 patients (groups A/B/C: 68/53/18 patients), radiation necrosis in 67 (24/31/12), and mixed/undetermined lesions in 6 (1/5/0). There were no significant differences in tumor recurrence or radiation necrosis between groups B and C. Multivariate analysis using the Fine-Gray proportional hazards model revealed age < 65 years, neurological symptoms, tumor volume ≥ 1 cm3, and prescription dose < 22 Gy to be significant poor prognostic factors for local tumor progression. In the subset of 558 case-matched patients (186 in each group), there were no significant differences between groups B and C in local tumor progression, nor in tumor recurrence or radiation necrosis.

CONCLUSIONS

Local tumor progression incidences did not differ between groups B and C. This study proved that tumor progression after GKRS without whole-brain radiation therapy for patients with 5–10 BMs was satisfactorily treated with the doses prescribed according to the JLGK0901 study protocol and that results were not inferior to those in patients with a single or 2–4 BMs.

Clinical trial registration no.: UMIN000001812 (umin.ac.jp)

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Ori Barzilai, Lily McLaughlin, Eric Lis, Yoshiya Yamada, Mark H. Bilsky and Ilya Laufer

OBJECTIVE

As patients with metastatic cancer live longer, an increased emphasis is placed on long-term therapeutic outcomes. The current study evaluates outcomes of long-term cancer survivors following surgery for spinal metastases.

METHODS

The study population included patients surgically treated at a tertiary cancer center between January 2010 and December 2015 who survived at least 24 months postoperatively. A retrospective chart and imaging review was performed to collect data regarding patient demographics; tumor histology; type and extent of spinal intervention; radiation data, including treatment dose and field; long-term sequelae, including local tumor control; and reoperations, repeat irradiation, or postoperative kyphoplasty at a previously treated level.

RESULTS

Eighty-eight patients were identified, of whom 44 were male, with a mean age of 61 years. The mean clinical follow-up for the cohort was 44.6 months (range 24.2–88.3 months). Open posterolateral decompression and stabilization was performed in 67 patients and percutaneous minimally invasive surgery in 21. In the total cohort, 84% received postoperative adjuvant radiation and 27% were operated on for progression following radiation. Posttreatment local tumor progression was identified in 10 patients (11%) at the index treatment level and 5 additional patients had a marginal failure; all of these patients were treated with repeat irradiation with 5 patients requiring a reoperation. In total, at least 1 additional surgical intervention was performed at the index level in 20 (23%) of the 88 patients: 11 for hardware failure, 5 for progression of disease, 3 for wound complications, and 1 for postoperative hematoma. Most reoperations (85%) were delayed at more than 3 months from the index surgery. Wound infections or dehiscence requiring additional surgical intervention occurred in 3 patients, all of which occurred more than a year postoperatively. Kyphoplasty at a previously operated level was performed in 3 cases due to progressive fractures.

CONCLUSIONS

Durable tumor control can be achieved in long-term cancer survivors surgically treated for symptomatic spinal metastases with limited complications. Complications observed after long-term follow-up include local tumor recurrence/progression, marginal tumor control failures, early or late hardware complications, late wound complications, and progressive spinal instability or deformity.

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Nils H. Ulrich, Jakob M. Burgstaller, Isaac Gravestock, Giuseppe Pichierri, Maria M. Wertli, Johann Steurer, Mazda Farshad and François Porchet

OBJECTIVE

In this retrospective analysis of a prospective multicenter cohort study, the authors assessed which surgical approach, 1) the unilateral laminotomy with bilateral spinal canal decompression (ULBD; also called “over the top”) or 2) the standard open bilateral decompression (SOBD), achieves better clinical outcomes in the long-term follow-up. The optimal surgical approach (ULBD vs SOBD) to treat lumbar spinal stenosis remains controversial.

METHODS

The main outcomes of this study were changes in a spinal stenosis measure (SSM) symptoms score, SSM function score, and quality of life (sum score of the 3-level version of the EQ-5D tool [EQ-5D-3L]) over time. These outcome parameters were measured at baseline and at 12-, 24-, and 36-month follow-ups. To obtain an unbiased result on the effect of ULBD compared to SOBD the authors used matching techniques relying on propensity scores. The latter were calculated based on a logistic regression model including relevant confounders. Additional outcomes of interest were raw changes in main outcomes and in the Roland and Morris Disability Questionnaire from baseline to 12, 24, and 36 months.

RESULTS

For this study, 277 patients met the inclusion criteria. One hundred forty-nine patients were treated by ULBD, and 128 were treated by SOBD. After propensity score matching, 128 patients were left in each group. In the matched cohort, the mean (95% CI) estimated differences between ULBD and SOBD for change in SSM symptoms score from baseline to 12 months were −0.04 (−0.25 to 0.17), to 24 months −0.07 (−0.29 to 0.15), and to 36 months −0.04 (−0.28 to 0.21). For change in SSM function score, the estimated differences from baseline to 12 months were 0.06 (−0.08 to 0.21), to 24 months 0.08 (−0.07 to 0.22), and to 36 months 0.01 (−0.16 to 0.17). Differences in changes between groups in EQ-5D-3L sum scores were estimated to be −0.32 (−4.04 to 3.40), −0.89 (−4.76 to 2.98), and −2.71 (−7.16 to 1.74) from baseline to 12, 24, and 36 months, respectively. None of the group differences between ULBD and SOBD were statistically significant.

CONCLUSIONS

Both surgical techniques, ULBD and SOBD, may provide effective treatment options for DLSS patients. The authors further determined that the patient outcome results for the technically more challenging ULBD seem not to be superior to those for the SOBD even after 3 years of follow-up.