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Alexis Dimitriadis and Ian Paddick

OBJECTIVE

Stereotactic radiosurgery (SRS) is characterized by high levels of conformity and steep dose gradients from the periphery of the target to surrounding tissue. Clinical studies have backed up the importance of these factors through evidence of symptomatic complications. Available data suggest that there are threshold doses above which the risk of symptomatic radionecrosis increases with the volume irradiated. Therefore, radiosurgical treatment plans should be optimized by minimizing dose to the surrounding tissue while maximizing dose to the target volume. Several metrics have been proposed to quantify radiosurgical plan quality, but all present certain weaknesses. To overcome limitations of the currently used metrics, a novel metric is proposed, the efficiency index (η50%), which is based on the principle of calculating integral doses: η50% = integral doseTV/integral dosePIV50%.

METHODS

The value of η50% can be easily calculated by dividing the integral dose (mean dose × volume) to the target volume (TV) by the integral dose to the volume of 50% of the prescription isodose (PIV50%). Alternatively, differential dose-volume histograms (DVHs) of the TV and PIV50% can be used. The resulting η50% value is effectively the proportion of energy within the PIV50% that falls into the target. This value has theoretical limits of 0 and 1, with 1 being perfect. The index combines conformity, gradient, and mean dose to the target into a single value. The value of η50% was retrospectively calculated for 100 clinical SRS plans.

RESULTS

The value of η50% for the 100 clinical SRS plans ranged from 37.7% to 58.0% with a mean value of 49.0%. This study also showed that the same principles used for the calculation of η50% can be adapted to produce an index suitable for multiple-target plans (Gη12Gy). Furthermore, the authors present another adaptation of the index that may play a role in plan optimization by calculating and minimizing the proportion of energy delivered to surrounding organs at risk (OARη50%).

CONCLUSIONS

The proposed efficiency index is a novel approach in quantifying plan quality by combining conformity, gradient, and mean dose into a single value. It quantifies the ratio of the dose “doing good” versus the dose “doing harm,” and its adaptations can be used for multiple-target plan optimization and OAR sparing.

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Bengt Karlsson, Arne V. Johansson, Huai-Che Yang, Hidefumi Jokura, Masaaki Yamamoto, Roberto Martínez-Álvarez, Jun Kawagishi, Wan-Yuo Guo, Guus Beute, David H. C. Pan, Wen-Yuh Chung, Michael Söderman, Hitoshi Aiyama and Tseng Tsai Yeo

OBJECTIVE

There is a strong clinical need to accurately determine the average annual hemorrhage risk in unruptured brain arteriovenous malformations (AVMs). This need motivated the present initiative to use data from a uniquely large patient population and design a novel methodology to achieve a risk determination with unprecedented accuracy. The authors also aimed to determine the impact of sex, pregnancy, AVM volume, and location on the risk for AVM rupture.

METHODS

The present study does not consider any specific management of the AVMs, but only uses the age distribution for the first hemorrhage, the shape of which becomes universal for a sufficiently large set of patients. For this purpose, the authors collected observations, including age at first hemorrhage and AVM size and location, in 3425 patients. The average annual risk for hemorrhage could then be determined from the simple relation that the number of patients with their first hemorrhage at a specific age equals the risk for hemorrhage times the number of patients at risk at that age. For a subset of the patients, the information regarding occurrence of AVM hemorrhage after treatment of the first hemorrhage was used for further analysis of the influence on risk from AVM location and pregnancy.

RESULTS

The age distribution for the first AVM hemorrhage was used to determine the average annual risk for hemorrhage in unruptured AVMs at adult ages (25–60 years). It was concluded to be 3.1% ± 0.2% and unrelated to AVM volume but influenced by its location, with the highest risk for centrally located AVMs. The hemorrhage risk was found to be significantly higher for females in their fertile years.

CONCLUSIONS

The present methodology allowed the authors to determine the average annual risk for the first AVM hemorrhage at 3.1% ± 0.2% without the need for individual patient follow-up. This methodology has potential also for other similar types of investigations. The conclusion that centrally located AVMs carry a higher risk was confirmed by follow-up information. Follow-up information was also used to conclude that pregnancy causes a substantially greater AVM hemorrhage risk. The age distribution for AVM hemorrhage is incompatible with AVMs present at birth having the same hemorrhage risk as AVMs in adults. Plausibly, they instead develop in the early years of life, possibly with a lower hemorrhage risk during that time period.

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Serge Makarenko, Vincent Ye, Peter A. Gooderham and Ryojo Akagami

OBJECTIVE

Historically, descriptions of visual acuity and visual field change following intracranial procedures have been very rudimentary. Clinicians and researchers have often used basic descriptions, such as “improved,” “worsened,” and “unchanged,” to describe outcomes following resections of tumors affecting the optic apparatus. These descriptors are vague, difficult to quantify, and challenging to apply in a clinical perspective. Several groups have attempted to combine visual acuity and visual fields into a single assessment score, but these are not user-friendly. The authors present a novel way to describe a patient’s visual function as a combination of visual acuity and visual field assessment that is simple to use and can be used by surgeons and researchers to gauge visual outcomes following tumor resection.

METHODS

Visual acuity and visual fields were combined into 3 categories designed around the definitions of legal blindness and fitness to drive in Canada. The authors then applied the scale (the Unified Visual Function Scale, or UVFS) to their previously published case series of perisellar meningiomas to document and test overall visual outcomes for patients undergoing tumor resection. The results were compared with previously documented visual loss scales in the literature.

RESULTS

Using the UVFS the authors were able to capture the overall visual change; the scale was sensitive enough to define the overall visual improvement or worsening quantitatively, using categories that are clinically relevant and understandable.

CONCLUSIONS

The UVFS is a robust way to assess a patient’s vision, combining visual fields and acuity. The implementation of pre- and postoperative assessment is sensitive enough to assess overall change while also providing clinically relevant information for surgeons, and allows for comparisons between treatment groups.

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Kirsten van Baarsen, Jonathan Roth, Natalia Serova, Roger J. Packer, Ben Shofty, Ulrich-W. Thomale, Giuseppe Cinalli, Helen Toledano, Shalom Michowiz and Shlomi Constantini

OBJECTIVE

Hemorrhage (also known as apoplexy) in optic pathway gliomas (OPGs) is rare. Because of the variable presentations and low incidence of OPG hemorrhages, little is known about their clinical course and the best treatment options. The aim of this work was to review risk factors, clinical course, and treatment strategies of optic glioma hemorrhages in the largest possible number of cases.

METHODS

A total of 34 patients were analyzed. Nine new cases were collected, and 25 were identified in the literature. Data regarding demographics, radiological and histological features, treatment, and outcome were retrospectively reviewed.

RESULTS

The majority of patients were younger than 20 years. Only 3 patients were known to have neurofibromatosis. The histopathological diagnosis was pilocytic astrocytoma in the majority of cases. Five patients had intraorbital hemorrhages, whereas 29 patients had intracranial hemorrhage; the majority of intracranial bleeds were treated surgically. Six patients, all with intracranial hemorrhage, died due to recurrent bleeding, hydrocephalus, or surgical complications. No clear risk factors could be identified.

CONCLUSIONS

Intracerebral OPG hemorrhages have a fatal outcome in 20% of cases. Age, hormonal status, neurofibromatosis involvement, and histopathological diagnosis have been suggested as risk factors for hemorrhage, but this cannot be reliably established from the present series. The goals of surgery should be patient survival and prevention of further neurological and ophthalmological deterioration.

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Rajiv R. Iyer, Xiaobu Ye, Qiuyu Jin, Yao Lu, Luckmini Liyanage and Edward S. Ahn

OBJECTIVE

Many infants with sagittal craniosynostosis undergo effective surgical correction with endoscopic strip craniectomy (ESC) and postoperative helmet therapy (PHT). While PHT is essential to achieving optimal cosmesis following ESC, there has been little comprehensive analysis of the ideal PHT duration needed to attain this goal.

METHODS

The authors retrospectively reviewed the charts of infants undergoing ESC and PHT for sagittal synostosis at our institution between 2008 and 2015. Data collected included age at surgery, follow-up duration, and PHT duration. Cephalic index (CI) was evaluated preoperatively (CIpre), at its peak level (CImax), at termination of helmet therapy (CIoff), and at last follow-up (CIfinal). A multivariate regression analysis was performed to determine factors influencing CIfinal.

RESULTS

Thirty-one patients (27 male, 4 female) were treated in the studied time period. The median age at surgery was 2.7 months (range 1.6 to 3.2) and the median duration of PHT was 10.4 months (range 8.4 to 14.4). The mean CImax was 0.83 (SD 0.01), which was attained an average of 8.4 months (SD 1.2) following PHT initiation. At last follow-up, there was an average retraction of CIfinal among all patients to 0.78 (SD 0.01). Longer helmet duration after achieving CImax did not correlate with higher CIfinal values. While CImax was a significant predictor of CIfinal, neither age at surgery nor CIpre were found to be predictive of final outcome.

CONCLUSIONS

Patients undergoing ESC and PHT for sagittal synostosis reach a peak CI around 7 to 9 months after surgery. PHT beyond CImax does not improve final anthropometric outcomes. CIfinal is significantly dependent on CImax, but not on age, nor CIpre. These results imply that helmet removal at CImax may be appropriate for ESC patients, while helmeting beyond the peak does not change final outcome.

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Morenikeji Buraimoh, Azam Basheer, Kevin Taliaferro, Jonathan H. Shaw, Sameah Haider, Gregory Graziano and Eugene Koh

Every day, spine surgeons call for instruments named after surgical pioneers. Few know the designers or the histories behind their instruments. In this paper the authors provide a historical perspective on the Penfield dissector, Leksell rongeur, Hibbs retractor, Woodson elevator, Kerrison rongeur, McCulloch retractor, Caspar pin retractor system, and Cloward handheld retractor, and a biographical review of their inventors. Historical data were obtained by searching the HathiTrust Digital Library, PubMed, Google Scholar, Google Books, and Google, and personal communications with relatives, colleagues, and foundations of the surgeon-designers. The authors found that the Penfield dissectors filled a need for delicate tools for manipulating the brain and that the Leksell rongeur increased surgical efficiency during war-related laminectomies. Hibbs’ retractor facilitated his spine fusion technique. Woodson was both a dentist and a physician whose instrument was adopted by spine surgeons. Kerrison rongeurs were developed in otology to decompress bone near the facial nerve. The McCulloch, Caspar, and Cloward retractors helped improve exposure during the emergence of new techniques, i.e., microdiscectomy and anterior cervical discectomy and fusion. The histories behind these eponymous instruments remind us that innovation sometimes begins in other specialties and demonstrate the role of innovation in improving patient care.

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Ahmed Jorge, Michael D. White and Nitin Agarwal

OBJECTIVE

Individuals with a spinal cord injury (SCI) in socioeconomically disadvantaged settings (e.g., rural or low income) have different outcomes than their counterparts; however, a contemporary literature review identifying and measuring these outcomes has not been published. Here, the authors’ aim was to perform a systematic review and identify these parameters in the hope of providing tangible targets for future clinical research efforts.

METHODS

A systematic review was performed to find English-language articles published from 2007 to 2017 in the PubMed/MEDLINE, EMBASE, and SCOPUS databases. Studies evaluating any outcomes related to patients with an SCI and in a low-resource setting were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and a flowchart was created. Of the 403 articles found, 31 underwent complete review and 26 were eligible for study inclusion. According to the current study criteria, any case studies, studies in less developed countries, studies including and not separating other types of neurological disorders, studies not assessing the effects of a low-resource setting on outcomes in patients with SCI, and studies evaluating the causes of SCI in a low-resource setting were excluded.

RESULTS

In SCI patients, a lower income was a predictor of death (OR 2.1, 95% CI 1.7–2.6, p = 0.0002). Moreover, secondary outcomes such as pain intensities (OR 3.32, 95% CI 2.21–4.49, p < 0.001), emergency room visits (11% more likely, p = 0.006), and pressure ulcer formation (OR 2.1, 95% CI 1.5–3.0, p < 0.001) were significantly higher in the lower income brackets. Rurality was also a factor and was significantly associated with increased emergency room visits (OR 1.5, 95% CI 1.1–2.1, p = 0.01) and lower outpatient service utilization (incidence rate ratio [IRR] 0.57, 95% CI 0.35–0.93, p < 0.05).

CONCLUSIONS

The authors showed that individuals in a low-resource setting who have suffered an SCI have significantly different outcomes than their counterparts. These specific outcomes are promising targets for future research efforts that focus on improving health conditions among this population.

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Craig G. van Horne, Jorge E. Quintero, John T. Slevin, Amelia Anderson-Mooney, Julie A. Gurwell, Andrew S. Welleford, John R. Lamm, Renee P. Wagner and Greg A. Gerhardt

OBJECTIVE

Currently, there is no treatment that slows or halts the progression of Parkinson’s disease. Delivery of various neurotrophic factors to restore dopaminergic function has become a focus of study in an effort to fill this unmet need for patients with Parkinson’s disease. Schwann cells provide a readily available source of such factors. This study presents a 12-month evaluation of safety and feasibility, as well as the clinical response, of implanting autologous peripheral nerve grafts into the substantia nigra of patients with Parkinson’s disease at the time of deep brain stimulation (DBS) surgery.

METHODS

Standard DBS surgery targeting the subthalamic nucleus was performed in 8 study participants. After DBS lead implantation, a section of the sural nerve containing Schwann cells was harvested and unilaterally grafted to the substantia nigra. Adverse events were continually monitored. Baseline clinical data were obtained during standard preoperative evaluations. Clinical outcome data were obtained with postoperative clinical evaluations, neuropsychological testing, and MRI at 1 year after surgery.

RESULTS

All 8 participants were implanted with DBS systems and grafts. Adverse event profiles were comparable to those of standard DBS surgery with the exception of 1 superficial infection at the sural nerve harvest site. Three participants also reported numbness in the distribution of the sural nerve distal to the harvest site. Motor scores on Unified Parkinson’s Disease Rating Scale (UPDRS) part III while the participant was off therapy at 12 months improved from baseline (mean ± SD 25.1 ± 15.9 points at 12 months vs 32.5 ± 9.7 points at baseline). An analysis of the lateralized UPDRS scores also showed a greater overall reduction in scores on the side contralateral to the graft.

CONCLUSIONS

Peripheral nerve graft delivery to the substantia nigra at the time of DBS surgery is feasible and safe based on the results of this initial pilot study. Clinical outcome data from this phase I trial suggests that grafting may have some clinical benefit and certainly warrants further study to determine if this is an efficacious and neurorestorative therapy.

Clinical trial registration no.: NCT01833364 (clinicaltrials.gov)

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John D. Heiss, Aria Jamshidi, Smit Shah, Staci Martin, Pamela L. Wolters, Davis P. Argersinger, Katherine E. Warren and Russell R. Lonser

OBJECTIVE

In this clinical trial report, the authors analyze safety and infusion distribution of IL13-Pseudomonas exotoxin, an antitumor chimeric molecule, administered via intratumoral convection enhanced delivery (CED) in pediatric patients with diffuse intrinsic pontine glioma (DIPG).

METHODS

This was a Phase I single-institution, open-label, dose-escalation, safety and tolerability study of IL13-PE38QQR infused via single-catheter CED into 5 pediatric DIPG patients. IL13-PE38QQR was administered to regions of tumor selected by radiographic findings. Two escalating dose levels were evaluated: 0.125 µg/mL in cohort 1 and 0.25 µg/mL in cohort 2. Real-time MRI was performed during intratumoral infusions, and MRI and MR spectroscopy were performed before and after the infusions. Clinical evaluations, including parent-reported quality of life (QOL), were assessed at baseline and 4 weeks post-infusion.

RESULTS

Direct infusion of brainstem tumor with IL13-PE using the CED technique in patients with DIPG produced temporary arrest of disease progression in 2 of 5 patients, both of whom subsequently received a second infusion. All 5 patients showed signs of disease progression by 12 weeks after initial infusion. Two patients experienced transient cranial nerve deficits and lethargy after infusion, and these deficits resolved with corticosteroid treatment in both cases. No patient had radiographic evidence of acute or long-term treatment toxicity. Parent-reported QOL was consistent with medical outcomes.

CONCLUSIONS

Even though IL13-PE delivered by CED did not reach the entire MRI-defined tumor volume in any patient, short-term radiographic antitumor effects were observed in 2 of the 5 patients treated. The patients’ performance status did not improve. Drug delivery using multiple catheters may produce improved outcomes.

Clinical trial registration no.: NCT00088061 (clinicaltrials.gov)

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Katsuhisa Yamada, Hideki Sudo, Kiyoshi Kaneda, Yasuhiro Shono, Yuichiro Abe and Norimasa Iwasaki

OBJECTIVE

The aim of this retrospective study was to analyze the influence of upper instrumented vertebra (UIV) translation from the C7 plumb line (C7PL) on the long-term postoperative results of patients with main thoracic (MT) adolescent idiopathic scoliosis (AIS).

METHODS

Twenty-five patients had been treated surgically for AIS with a Lenke type 1 curve and had been followed up for a mean period of 18.2 years. Radiographic parameters, pulmonary function measurements, and clinical outcomes were compared between the patients (n = 15) with UIV translation < 20 mm and those (n = 10) with UIV translation ≥ 20 mm at the final follow-up. Correlations between UIV translation and radiographic or pulmonary function parameters were analyzed.

RESULTS

Patients with ≥ 20 mm UIV translation at the final follow-up had a significantly larger preoperative UIV translation than that in the patients with < 20 mm UIV translation at follow-up. The former group also had a significantly lower correction rate of the MT curve, higher chest cage ratio, and lower radiographic shoulder height (p = 0.01, 0.005, and 0.025, respectively) at the final follow-up. The Scoliosis Research Society (SRS)–30 Questionnaire scores were equivalent between the two groups. Correlation analysis showed that the following parameters were significantly associated with UIV translation: MT curve correction rate (r = -0.481, p = 0.015), chest cage ratio (r = 0.673, p < 0.001), and percent-predicted forced expiratory volume in 1 second (r = -0.455, p = 0.033).

CONCLUSIONS

The UIV translation should be considered an important factor that influences postoperative results. In MT AIS patients whose preoperative upper end vertebra (UEV) is distant from the C7PL, the UIV should be selected above the UEV to prevent large UIV translation at the postoperative follow-up.