Radiographic and Clinical Outcomes After Stand-Alone Anterior Lumbar Interbody Fusion for Symptomatic L5-S1 Retrolisthesis.

BACKGROUND AND OBJECTIVES: Degenerative lumbar spondylolisthesis is associated with significant pain and disability. The literature on the treatment options and clinical outcomes for lumbar anterolisthesis is robust, but very few reports specifically evaluate lumbar retrolisthesis. This study investigated surgical outcomes for symptomatic L5-S1 retrolisthesis treated with stand-alone L5-S1 anterior lumbar interbody fusion (ALIF). METHODS: All patients with symptomatic L5-S1 retrolisthesis treated with stand-alone L5-S1 ALIF at a single institution over a 7-year period were identified. Exhaustive nonoperative management had failed for all patients. Patients with previous lumbar fusion were excluded. Preoperative and postoperative radiographic images and patient-reported outcome measures for 20 patients (14 males and 6 females; mean [SD] age, 50.3 [13.7] years) were analyzed. RESULTS: The mean (SD) follow-up was 43.0 (23.7) months (range, 12.1-102.5 months). Patients experienced postoperative improvements in L5-S1 retrolisthesis (P = .048), L5-S1 disk height and angle (P < .001), L5 foraminal height (P < .001), L5-S1 lordosis (P < .001), and lumbar lordosis (P = .01). There were no significant changes in spinopelvic parameters. At the most recent follow-up, minimal clinically important differences in Oswestry Disability Index score, 36-Item Short-Form Survey (SF-36), and numerical rating scale score for leg pain were achieved in 11 of 20 (55%), 7 of 14 (50%), and 7 of 13 (54%) patients, respectively. All patients demonstrated fusion with no graft subsidence at up to 32 months. No patient experienced intraoperative complications, was readmitted, or required a subsequent posterior decompression or fusion because of refractory symptoms. CONCLUSION: In our cohort, stand-alone L5-S1 ALIF was associated with radiographic and clinical improvement in patients with symptomatic L5-S1 retrolisthesis.

Management of hangman's fractures using anchored anterior cervical cages.

Background: Hangman's fractures comprise approximately 20% of C2 fractures and often require surgery to correct significant angulation and/or subluxation. Recently, anchored anterior cervical cages (ACCs) have been used to fuse C2-3 as they reduce the risks of soft-tissue dissection, bone drilling, operative time, and postoperative dysphagia. Methods: This single-center and retrospective study (2012-2019) included 12 patients (3 type I, 6 type II, and 3 type IIa fractures) undergoing C2-3 ACCs (zero profile, half plate, full plate). Preoperative and postoperative radiographic and clinical data were analyzed. Results: The 12 patients demonstrated the following findings: a mean operative time of 106 ± 21 min, blood loss averaging 67 ± 58 mL, and mean length of stay of 9.8 ± 7.7 days (6.4 ± 5.5 days in intensive care). The mean differences in preoperative versus postoperative radiographs showed an increase in disc angle (9.0° ± 9.4° vs. 14.0° ± 7.2°), reduction of subluxation (18.5% ± 13.6% vs. 2.6% ± 6.2%), and maintenance of C2-7 lordosis (14.3° ± 9.5° vs. 14.4° ± 9.5°). All patients demonstrated fusion on dynamic films obtained >6 months postoperatively. In addition, only one patient had Grade 0 subsidence, three had transient postoperative dysphagia, whereas none had either intraoperative complications or 90-day readmissions. Conclusion: ACCs proved to be a viable alternative to traditional anterior cervical discectomy/fusion to treat 12 patients with C2-3 hangman's fractures in this preliminary study.

Second window ICG predicts postoperative MRI gadolinium enhancement in high grade gliomas and brain metastases.

A prospective trial evaluating the utility of second window indocyanine green (SWIG) in predicting postoperative MRI gadolinium enhancement was performed on high-grade gliomas (HGGs) and brain metastases. Compared to white light alone, SWIG demonstrated a higher sensitivity, negative predictive value, and accuracy in predicting residual neoplasm on MRI. The specificity of SWIG for predicting MRI enhancement was higher in HGGs than brain metastases. Clinically, near-infrared (NIR) imaging was better able to predict tumor recurrence than postoperative MRI. These results illustrate how SWIG is able to take advantage of gadolinium-like distribution properties to extravasate into the tumor microenvironment, enabling guidance in surgical resection. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21204.

Stereotactic-Guided Transcerebellar Cisternoperitoneal Shunt Placement for Idiopathic Intracranial Hypertension.

BACKGROUND: Idiopathic intracranial hypertension (IIH) can cause debilitating symptoms and optic nerve ischemia if untreated. Cerebrospinal fluid diversion is often necessary to reduce intracranial pressure; however, current ventriculoperitoneal and lumboperitoneal shunting techniques have high failure rates in patients with IIH. OBJECTIVE: To describe our experience treating IIH with a novel stereotactic-guided transcerebellar cisternoperitoneal shunt (SGTC-CPS) technique that places the proximal shunt catheter in the posterior cisterna magnum. METHODS: Retrospective perioperative and postoperative data from all patients who underwent SGTC-CPS placement for IIH from March 1, 2015, to December 31, 2020, were analyzed. Patients were positioned as for ventriculoperitoneal shunt placement but with the head turned farther laterally to adequately expose the retrosigmoid space. Using neuronavigation, an opening was made near the transverse-sigmoid junction, and the proximal catheter was inserted transcerebellarly into the posterior foramen magnum. RESULTS: Thirty-two patients underwent SGTC-CPS placement (29 female; mean body mass index, 36.0 ± 7.5; 14 with prior shunt failures). The mean procedure time for shunt placement was 145 minutes. No intraoperative complications occurred, and all patients were discharged uneventfully. At the 6-month follow-up, 81% of patients (21 of 26) had relief of their presenting symptoms. Shunt survival without revision was 86% (25 of 29) at 1 year and 67% (10 of 15) at 3 years, with no infections. CONCLUSION: The SGTC-CPS offers an alternative solution for cerebrospinal fluid diversion in patients with IIH and demonstrates a lower failure rate and more durable symptom relief compared with ventriculoperitoneal or lumboperitoneal shunt placement. Using proper techniques and equipment promotes safe and facile placement of the proximal catheter.

Assessment and Comparison of Three Dimensional Exoscopes for Near-Infrared Fluorescence-Guided Surgery Using Second-Window Indocyanine-Green.

OBJECTIVE: Compared to microscopes, exoscopes have advantages in field-depth, ergonomics, and educational value. Exoscopes are especially well-poised for adaptation into fluorescence-guided surgery (FGS) due to their excitation source, light path, and image processing capabilities. We evaluated the feasibility of near-infrared FGS using a 3-dimensional (3D), 4 K exoscope with nearinfrared fluorescence imaging capability. We then compared it to the most sensitive, commercially-available near-infrared exoscope system (3D and 960 p). In-vitro and intraoperative comparisons were performed. METHODS: Serial dilutions of indocyanine-green (1-2000 µg/mL) were imaged with the 3D, 4 K Olympus Orbeye (system 1) and the 3D, 960 p VisionSense Iridium (system 2). Near-infrared sensitivity was calculated using signal-to-background ratios (SBRs). In addition, three patients with brain tumors were administered indocyanine-green and imaged with system 1, with two also imaged with system 2 for comparison. RESULTS: Systems 1 and 2 detected near-infrared fluorescence from indocyanine green concentrations of >250 µg/L and >31.3 µg/L, respectively. Intraoperatively, system 1 visualized strong near-infrared fluorescence from two, strongly gadoliniumenhancing meningiomas (SBR=2.4, 1.7). The high-resolution, bright images were sufficient for the surgeon to appreciate the underlying anatomy in the near-infrared mode. However, system 1 was not able to visualize fluorescence from a weakly-enhancing intraparenchymal metastasis. In contrast, system 2 successfully visualized both the meningioma and the metastasis but lacked high resolution stereopsis. CONCLUSION: Three-dimensional exoscope systems provide an alternative visualization platform for both standard microsurgery and near-infrared fluorescent guided surgery. However, when tumor fluorescence is weak (i.e., low fluorophore uptake, deep tumors), highly sensitive near-infrared visualization systems may be required.

The Evolution of 5-Aminolevulinic Acid Fluorescence Visualization: Time for a Headlamp/Loupe Combination.

BACKGROUND: The use of 5-aminolevulinic acid (5-ALA) for intraoperative protoporphyrin IX fluorescent imaging in the resection of malignant gliomas has been demonstrated to improve tumor visualization, increase the extent of resection, and extend progression-free survival. The current technique for visualization of 5-ALA consists of excitation and emission filters built into the operating microscope. However, there are notable limitations to this process, including low quantum yield, expense, and masking of surrounding anatomy. METHODS: We present 3 cases in which 3 separate methods were employed for visualizing fluorescence. The devices reported are 1) a low-cost blue light flashlight, 2) a low-cost headlamp, and 3) the first reported case of the new Designs for Vision REVEAL Fluorescence-Guided Surgery (FGS) 5-ALA fluorescent headlight and loupes. The aim of the study is to provide confirmation that tumor fluorescence can be observed using commercially available products other than the microscope. RESULTS: We demonstrate through 3 intraoperative cases that a variety of devices can produce visible fluorescence of the high-grade tumor and allow for simultaneous real-time visualization of the adjacent brain parenchyma and vasculature. The REVEAL FGS system appears to offer increased fluorescence emission compared with all other methods, including the microscope. CONCLUSIONS: Our study demonstrates the feasibility of using blue/ultraviolet light supplied by a commercially available, inexpensive flashlight or headlamp to visualize 5-ALA fluorescence in high-grade gliomas. We also provide the first documentation of the intraoperative use of the new Designs for Vision REVEAL FGS 5-ALA fluorescent headlight and loupes and report on the experience. Lack of an operative microscope capable of fluorescent illumination should not be a limiting factor in performing fluorescent-guided glioma resection.

REV-ERB nuclear receptors in the suprachiasmatic nucleus control circadian period and restrict diet-induced obesity.

Circadian disruption, as occurs in shift work, is associated with metabolic diseases often attributed to a discordance between internal clocks and environmental timekeepers. REV-ERB nuclear receptors are key components of the molecular clock, but their specific role in the SCN master clock is unknown. We report here that mice lacking circadian REV-ERB nuclear receptors in the SCN maintain free-running locomotor and metabolic rhythms, but these rhythms are notably shortened by 3 hours. When housed under a 24-hour light:dark cycle and fed an obesogenic diet, these mice gained excess weight and accrued more liver fat than controls. These metabolic disturbances were corrected by matching environmental lighting to the shortened endogenous 21-hour clock period, which decreased food consumption. Thus, SCN REV-ERBs are not required for rhythmicity but determine the free-running period length. Moreover, these results support the concept that dissonance between environmental conditions and endogenous time periods causes metabolic disruption.

Second window ICG predicts gross-total resection and progression-free survival during brain metastasis surgery.

OBJECTIVE: Metastases are the most common intracranial malignancies and complete resection can provide relief of neurological symptoms and reduce recurrence. The authors' prospective pilot study in 2017 demonstrated promising results for the application of high-dose, delayed imaging of indocyanine green (ICG), known as second window ICG (SWIG), in patients undergoing surgery for brain metastases. In this prospective cohort study, the authors evaluated intraoperative imaging and clinical outcomes of treatment using SWIG. METHODS: Patients were prospectively enrolled in an approved study of high-dose, delayed ICG (SWIG) and received 5 mg/kg (2014-2018) or 2.5 mg/kg (2018-2019) ICG 24 hours preoperatively. Intraoperatively, near-infrared (NIR) imaging was performed using a dedicated NIR exoscope. NIR images were analyzed and the signal-to-background ratio (SBR) was calculated to quantify fluorescence. Residual fluorescence on the postresection NIR view was compared and correlated to the residual gadolinium enhancement on postoperative MRI. Patient survival and predictive factors were analyzed. RESULTS: In total, 51 intracranial metastases were surgically treated in 47 patients in this cohort. All 51 metastatic tumors demonstrated strong NIR fluorescence (mean SBR 4.9). In tumors ≤ 10 mm from the cortical surface, SWIG with 5 mg/kg ICG produced enhanced transdural tumor visibility (91.3%) compared to 2.5 mg/kg (52.9%; p = 0.0047). Neoplastic margin detection using NIR fluorescence compared to white light improved sensitivity, albeit lowered specificity; however, increasing the SBR cutoff for positive fluorescence significantly improved specificity without sacrificing sensitivity, increasing the overall accuracy from 57.5% to 72.5%. A lack of residual NIR fluorescence after resection was closely correlated with a lack of residual enhancement on postoperative MRI (p = 0.007). Among the 16 patients in whom tumor recurred at the site of surgery, postoperative MRI successfully predicted 8 cases, whereas the postresection NIR view predicted 12 cases. Progression-free survival rate at 12 months was greater for patients without residual NIR fluorescence (38%) than for those without residual enhancement on postoperative MRI (29%). CONCLUSIONS: The current study demonstrates the clinical benefits of the SWIG technique in surgery for patients with brain metastases. Specifically, this technique allows for dose-dependent, transdural localization of neoplasms and improved sensitivity in neoplastic margin detection. Postresection residual fluorescence can be a powerful tool to evaluate extent of resection in conjunction with MRI, and it may guide decisions on brain metastasis management.

Somatostatin Receptor as a Molecular Imaging Target in Human and Canine Cushing Disease.

OBJECTIVES: Fluorescence-guided surgery may improve completeness of resection in transsphenoidal surgery for Cushing disease (CD) by enabling visualization of residual tumor tissue at the margins. In this review we discuss somatostatin receptors (SSTRs) as targets for fluorescence-guided surgery and overview existing SSTR-specific imaging agents. We also compare SSTR expression in normal pituitary and corticotrophinoma tissues from human and canine CD patients to assess canines as a translational model for CD. METHODS: A PubMed literature search was conducted for publications containing the terms canine, somatostatin receptor, Cushing's disease, and corticotroph adenoma. SSTR expression data from each study was documented as the presence or absence of expression or, when possible, the number of tumors expressing a given SSTR subtype within a group of tumors being studied. Studies that used reverse transcription polymerase chain reaction to quantify SSTR expression were selected for additional comparative analysis. RESULTS: SSTR5 is strongly expressed in human corticotroph adenomas and weakly expressed in surrounding pituitary parenchyma, a pattern not conclusively observed in canine patients. SSTR2 mRNA expression is similar in human normal pituitary and corticotrophinoma cells but may be significantly higher in canine normal pituitary tissue than in corticotroph tumoral tissue. Limited data were available on SSTR subtypes 1, 3, and 4. CONCLUSIONS: Further studies must fill the knowledge gaps related to species-specific SSTR expression, so using canine CD as a translational model may be premature. We do conclude that the expression profile of SSTR5 (i.e., high local expression in pituitary adenomas relative to normal surrounding tissues) makes SSTR5 a promising molecular target for FGS.

Applications of indocyanine green in brain tumor surgery: review of clinical evidence and emerging technologies.

Indocyanine green (ICG) is a water-soluble dye that was approved by the FDA for biomedical purposes in 1956. Initially used to measure cardiocirculatory and hepatic functions, ICG's fluorescent properties in the near-infrared (NIR) spectrum soon led to its application in ophthalmic angiography. In the early 2000s, ICG was formally introduced in neurosurgery as an angiographic tool. In 2016, the authors' group pioneered a novel technique with ICG named second-window ICG (SWIG), which involves infusion of a high dose of ICG (5.0 mg/kg) in patients 24 hours prior to surgery. To date, applications of SWIG have been reported in patients with high-grade gliomas, meningiomas, brain metastases, pituitary adenomas, craniopharyngiomas, chordomas, and pinealomas.The applications of ICG have clearly expanded rapidly across different specialties since its initial development. As an NIR fluorophore, ICG has advantages over other FDA-approved fluorophores, all of which are currently in the visible-light spectrum, because of NIR fluorescence's increased tissue penetration and decreased autofluorescence. Recently, interest in the latest applications of ICG in brain tumor surgery has grown beyond its role as an NIR fluorophore, extending into shortwave infrared imaging and integration into nanotechnology. This review aims to summarize reported clinical studies on ICG fluorescence-guided surgery of intracranial tumors, as well as to provide an overview of the literature on emerging technologies related to the utility of ICG in neuro-oncological surgeries, including the following aspects: 1) ICG fluorescence in the NIR-II window; 2) ICG for photoacoustic imaging; and 3) ICG nanoparticles for combined diagnostic imaging and therapy (theranostic) applications.

Second-Window Indocyanine Green for Visualization of Hemangioblastoma: A Case Report With Two-Dimensional Operative Video.

BACKGROUND AND IMPORTANCE: The proper differentiation of neoplastic tissue from adjacent brain parenchyma can pose a great challenge, especially in eloquent areas of the brain. With the novel technique, "Second-Window Indocyanine Green," injection of a near-infrared fluorophore (ICG) allows for intraoperative visualization of tumors by taking advantage of the compromised vasculature surrounding the tumor. Thus, such a technique may demonstrate utility for hemangioblastomas, which are hypervascular tumors of the central nervous system. CLINICAL PRESENTATION: Here we present the case of a 39-yr-old male with a demonstrated cystic mass in the left cerebellum, with additional edema spreading towards the vermis. A total of 5 mg/kg of ICG was delivered intravenously 24 h prior to the operation. The tumor was approached via the infratentorial suboccipital approach. We observed strong near-infrared fluorescence through the intact dura, consistent with the tumor location. Surgical pathology confirmed a final diagnosis of cerebellar hemangioblastoma. There was complete resection of the tumor, with the patient discharged uneventfully. CONCLUSION: We report the first successful case of fluorescence-guided surgery of a cerebellar hemangioblastoma using near-infrared fluorescence imaging with the Second-Window ICG technique. This joins a growing series of publications that demonstrate the efficacy of a novel application of ICG, a near-infrared fluorophore, in accurate intraoperative visualization of neoplastic tissue. While the use of a dedicated near-infrared platform (ie, the VisionSense Iridium [Visionsense, Philadelphia, Pennsylvania]) yields a higher signal-to-background ratio, a neurosurgical microscope (ie, the Leica OH6 [Leica Microsystems, Wetzlar, Germany]) may also provide a suitable option in cases where fluorescence is very strong.

Hypothalamic REV-ERB nuclear receptors control diurnal food intake and leptin sensitivity in diet-induced obese mice.

Obesity occurs when energy expenditure is outweighed by energy intake. Tuberal hypothalamic nuclei, including the arcuate nucleus (ARC), ventromedial nucleus (VMH), and dorsomedial nucleus (DMH), control food intake and energy expenditure. Here we report that, in contrast with females, male mice lacking circadian nuclear receptors REV-ERBα and -ß in the tuberal hypothalamus (HDKO mice) gained excessive weight on an obesogenic high-fat diet due to both decreased energy expenditure and increased food intake during the light phase. Moreover, rebound food intake after fasting was markedly increased in HDKO mice. Integrative transcriptomic and cistromic analyses revealed that such disruption in feeding behavior was due to perturbed REV-ERB-dependent leptin signaling in the ARC. Indeed, in vivo leptin sensitivity was impaired in HDKO mice on an obesogenic diet in a diurnal manner. Thus, REV-ERBs play a crucial role in hypothalamic control of food intake and diurnal leptin sensitivity in diet-induced obesity.

A Department Approach to Teleneurology.

The coronavirus disease-19 (COVID-19) pandemic has compelled health care practices and academic departments to evaluate the suitability of telemedicine for various specialties and attempt rapid implementation to enable continuation of health care that is safe for providers and patients. Many patients with neurological disorders are well suited to evaluations through video. The department of neurology at the University of Pennsylvania (Penn Neurology), with the support of the health system, rapidly expanded telemedicine services to meet the needs of our patient population. This accomplishment required the complex coordination of multiple disciplines and roles within the department and the health care system, including faculty, residents, administrative staff, research and technical staff, information services, and the connected health team. Procedures for provider and patient education were established. Surveys of the provider and patient experience were developed and deployed. The process has demonstrated the vital role telemedicine in neurology (teleneurology) should play in the care of neurological patients beyond the pandemic. We describe our experience as a template for other departments and practices seeking to establish teleneurology programs, as well as an illustration of the challenges and barriers to its implementation.

Combined fluorescence-guided surgery and photodynamic therapy for glioblastoma multiforme using cyanine and chlorin nanocluster.

INTRODUCTION: Glioblastoma multiforme (GBM) is the most common primary intracranial malignancy; survival can be improved by maximizing the extent-of-resection. METHODS: A near-infrared fluorophore (Indocyanine-Green, ICG) was combined with a photosensitizer (Chlorin-e6, Ce6) on the surface of superparamagnetic-iron-oxide-nanoparticles (SPIONs), all FDA-approved for clinical use, yielding a nanocluster (ICS) using a microemulsion. The physical-chemical properties of the ICS were systematically evaluated. Efficacy of photodynamic therapy (PDT) was evaluated in vitro with GL261 cells and in vivo in a subtotal resection trial using a syngeneic flank tumor model. NIR imaging properties of ICS were evaluated in both a flank and an intracranial GBM model. RESULTS: ICS demonstrated high ICG and Ce6 encapsulation efficiency, high payload capacity, and chemical stability in physiologic conditions. In vitro cell studies demonstrated significant PDT-induced cytotoxicity using ICS. Preclinical animal studies demonstrated that the nanoclusters can be detected through NIR imaging in both flank and intracranial GBM tumors (ex: 745 nm, em: 800 nm; mean signal-to-background 8.5 ± 0.6). In the flank residual tumor PDT trial, subjects treated with PDT demonstrated significantly enhanced local control of recurrent neoplasm starting on postoperative day 8 (23.1 mm3 vs 150.5 mm3, p = 0.045), and the treatment effect amplified to final mean volumes of 220.4 mm3 vs 806.1 mm3 on day 23 (p = 0.0055). CONCLUSION: A multimodal theragnostic agent comprised solely of FDA-approved components was developed to couple optical imaging and PDT. The findings demonstrated evidence for the potential theragnostic benefit of ICS in surgical oncology that is conducive to clinical integration.

Evaluation of Diagnostic Accuracy Following the Coadministration of Delta-Aminolevulinic Acid and Second Window Indocyanine Green in Rodent and Human Glioblastomas.

PURPOSE: Fluorescence-guided-surgery offers intraoperative visualization of neoplastic tissue. Delta-aminolevulinic acid (5-ALA), which targets enzymatic abnormality in neoplastic cells, is the only approved agent for fluorescence-guided neurosurgery. More recently, we described Second Window Indocyanine Green (SWIG) which targets neoplastic tissue through enhanced vascular permeability. We hypothesized that SWIG would demonstrate similar clinical utility in identification of high-grade gliomas compared with 5-ALA. PROCEDURES: Female C57/BL6 and nude/athymic mice underwent intracranial implantation of 300,000 GL261 and U87 cells, respectively. Tumor-bearing mice were euthanized after administration of 5-ALA (200 mg/kg intraperitoneal) and SWIG (5 mg/kg intravenous). Brain sections were imaged for protoporphyrin-IX and ICG fluorescence. Fluorescence and H&E images were registered using semi-automatic scripts for analysis. Human subjects with HGG were administered SWIG (2.5 mg/kg intravenous) and 5-ALA (20 mg/kg oral). Intraoperatively, tumors were imaged for ICG and protoporphyrin-IX fluorescence. RESULTS: In non-necrotic tumors, 5-ALA and SWIG demonstrated 90.2 % and 89.2 % tumor accuracy (p value = 0.52) in U87 tumors and 88.1 % and 87.7 % accuracy (p value = 0.83) in GL261 tumors. The most distinct difference between 5-ALA and SWIG distribution was seen in areas of tumor-associated necrosis, which often showed weak/no protoporphyrin-IX fluorescence, but strong SWIG fluorescence. In twenty biopsy specimens from four subjects with HGG, SWIG demonstrated 100 % accuracy, while 5-ALA demonstrated 75-85 % accuracy; there was 90 % concordance between SWIG and 5-ALA fluorescence. CONCLUSION: Our results provide the first direct comparison of the diagnostic utility of SWIG vs 5-ALA in both rodent and human HGG. Given the broader clinical utility of SWIG compared with 5-ALA, our data supports the use of SWIG in tumor surgery to improve the extent of safe resections. CLINICAL TRIAL: NCT02710240 (US National Library of Medicine Registry; https://www.clinicaltrials.gov/ct2/show/NCT02710240?id=NCT02710240&draw=2&rank=1 ).

Telemedicine in the Era of Coronavirus Disease 2019 (COVID-19): A Neurosurgical Perspective.

Despite the substantial growth of telemedicine and the evidence of its advantages, the use of telemedicine in neurosurgery has been limited. Barriers have included medicolegal issues surrounding provider reimbursement, interstate licensure, and malpractice liability as well as technological challenges. Recently, the coronavirus disease 2019 (COVID-19) pandemic has limited typical evaluation of patients with neurologic issues and resulted in a surge in demand for virtual medical visits. Meanwhile, federal and state governments took action to facilitate the rapid implementation of telehealth programs, placing a temporary lift on medicolegal barriers that had previously limited its expansion. This created a unique opportunity for widespread telehealth use to meet the surge in demand for remote medical care. After initial hurdles and challenges, our experience with telemedicine in neurosurgery at Penn Medicine has been overall positive from both the provider and the patients' perspective. One of the unique challenges we face is guiding patients to appropriately set up devices in a way that enables an effective neuroexamination. However, we argue that an accurate and comprehensive neurologic examination can be conducted through a telemedicine platform, despite minor weaknesses inherent to absence of physical presence. In addition, certain neurosurgical visits such as postoperative checks, vascular pathology, and brain tumors inherently lend themselves to easier evaluation through telehealth visits. In the era of COVID-19 and beyond, telemedicine remains a promising and effective approach to continue neurologic patient care.

Surface-Registration Frameless Stereotactic Navigation Is Less Accurate During Prone Surgeries: Intraoperative Near-Infrared Visualization Using Second Window Indocyanine Green Offers an Adjunct.

BACKGROUND: Frameless neuronavigation allows neurosurgeons to visualize and relate the position of surgical instruments to intracranial pathologies based on preoperative tomographic imaging. However, neuronavigation can often be inaccurate. Multiple factors have been proposed as potential causes, and new technologies are needed to overcome these challenges. OBJECTIVE: To evaluate the accuracy of neuronavigation systems compared to near-infrared (NIR) fluorescence imaging using Second Window Indocyanine Green, a novel technique, and to determine factors that lead to neuronavigation errors. METHODS: A retrospective analysis was conducted on 56 patients who underwent primary resections of intracranial tumors. Patients received 5 mg/kg ICG approximately 24 h preoperatively. Intraoperatively, neuronavigation was used to plan craniotomies to place the tumors in the center. After craniotomy, NIR imaging visualized tumor-specific NIR signals. The accuracy of neuronavigation and NIR fluorescence imaging for delineating the tumor boundary prior to durotomy was compared. RESULTS: The neuronavigation centers and NIR centers were 23.0 ± 7.7 % and 2.6 ± 1.1 % deviated from the tumor centers, respectively, relative to the craniotomy sizes. In 12 cases, significant changes were made to the planned durotomy based on NIR imaging. Patient position was a significant predictor of neuronavigation inaccuracy on both univariate and multivariate analysis, with the prone position having significantly higher inaccuracy (29.2 ± 8.1 %) compared to the supine (16.2 ± 8.1 %, p value < 0.001) or the lateral (17.9 ± 5.1 %, p value = 0.003) positions. CONCLUSION: Patient position significantly affects neuronavigation accuracy. Intraoperative NIR fluorescence imaging before durotomy offers an opportunity to readjust the neuronavigation image space to better align with the patient space.

Near-Infrared Fluorescence with Second-Window Indocyanine Green as an Adjunct to Localize the Pituitary Stalk During Skull Base Surgery.

A potential application of near-infrared (NIR) fluorescence imaging using second-window indocyanine green (SWIG) is demonstrated. We hypothesized that because the pituitary lacks a blood-brain barrier, we might visualize the pituitary stalk using SWIG. A 52-year-old, right-handed man presented to our clinic for evaluation of progressive loss of vision. Physical examination was significant for loss of right peripheral vision and near-complete loss of left field vision. Prolactin was high-normal at 16.2 mg/dL. Brain magnetic resonance imaging demonstrated a 36-mm sellar mass extending superiorly and laterally crossing the intracranial left internal carotid artery, consistent with a nonfunctional pituitary macroadenoma. We elected to pursue left pterional craniotomy for resection. The patient was eligible for our SWIG clinical trial and consented to the study. SWIG is a novel, investigational technique using Food and Drug Administration-approved indocyanine green to enhance visualization of neoplastic tissue intraoperatively.1-7 The patient received 2.5 mg/kg of indocyanine green intravenously approximately 24 hours preoperatively. Intraoperatively, under white-light microscopy, the tumor was easily identified and distinguished from the optic nerves and internal carotid artery. After debulking of the gross tumor, NIR visualization using a laser-equipped endoscope8 demonstrated strong NIR fluorescence in the pituitary stalk. Despite the distorted anatomy, this technique enabled us to confidently identify and preserve the pituitary stalk. Postoperatively, the patient had persistently high urine output that normalized in 24 hours without desmopressin (sodium 139-140 mmol/L); after uneventful recovery, he was discharged with mild improvement in visual function. This case demonstrated a potential use of our SWIG protocol. As the stalk demonstrates strong NIR fluorescence after high-dose indocyanine green administration, surgeons may be able to better localize and preserve the stalk even in complex skull base tumor cases where the anatomy may be significantly distorted.

Near-Infrared Imaging with Second-Window Indocyanine Green in Newly Diagnosed High-Grade Gliomas Predicts Gadolinium Enhancement on Postoperative Magnetic Resonance Imaging.

PURPOSE: Intraoperative molecular imaging with tumor-targeting fluorophores offers real-time detection of neoplastic tissue. The second window indocyanine green (SWIG) technique relies on passive accumulation of indocyanine green (ICG), a near-infrared fluorophore, in neoplastic tissues. In this study, we explore the ability of SWIG to detect neoplastic tissue and to predict postoperative magnetic resonance imaging (MRI) findings intraoperatively. PROCEDURES: Retrospective data were collected from 36 patients with primary high-grade gliomas (HGG) enrolled as part of a larger trial between October 2014 and October 2018. Patients received systemic ICG infusions at 2.5-5 mg/kg 24 h preoperatively. Near-infrared fluorescence was recorded throughout the case and from biopsy specimens. The presence/location of residual SWIG signal after resection was compared to the presence/location of residual gadolinium enhancement on postoperative MRI. The extent of resection was not changed based on near-infrared imaging. RESULTS: All 36 lesions demonstrated strong near-infrared fluorescence (signal-to-background = 6.8 ± 2.2) and 100 % of tumors reaching the cortex were visualized before durotomy. In 78 biopsy specimens, near-infrared imaging demonstrated higher sensitivity and accuracy than white light for diagnosing neoplastic tissue intraoperatively. Furthermore, near-infrared imaging predicted gadolinium enhancement on postoperative MRI with 91 % accuracy, with visualization of residual enhancement as small as 0.3 cm3. Patients with no residual near-infrared signal after resection were significantly more likely to have complete resection on postoperative MRI (p value < 0.0001). CONCLUSIONS: Intraoperative imaging with SWIG demonstrates highly sensitive detection of HGG tissue in real time. Furthermore, post-resection near-infrared imaging correlates with postoperative MRI. Overall, our findings suggest that SWIG can provide surgeons with MRI-like results in real time, potentially increasing resection rates.