Toward an optimal cadaveric brain model for neurosurgical education: assessment of preservation, parenchyma, vascular injection, and imaging.

OBJECTIVE: We assessed types of cadaveric head and brain tissue specimen preparations that are used in a high throughput neurosurgical research laboratory to determine optimal preparation methods for neurosurgical anatomical research, education, and training. METHODS: Cadaveric specimens (N = 112) prepared using different preservation and vascular injection methods were imaged, dissected, and graded by 11 neurosurgeons using a 21-point scale. We assessed the quality of tissue and preservation in both the anterior and posterior circulations. Tissue quality was evaluated using a 9-point magnetic resonance imaging (MRI) scale. RESULTS: Formalin-fixed specimens yielded the highest scores for assessment (mean ± SD [17.0 ± 2.8]) vs. formalin-flushed (17.0 ± 3.6) and MRI (6.9 ± 2.0). Cadaver assessment and MRI scores were positively correlated (P < 0.001, R2 0.60). Analysis showed significant associations between cadaver assessment scores and specific variables: nonformalin fixation (ß = -3.3), preservation within ≤72 h of death (ß = 1.8), and MRI quality score (ß = 0.7). Formalin-fixed specimens exhibited greater hardness than formalin-flushed and nonformalin-fixed specimens (P ≤ 0.006). Neurosurgeons preferred formalin-flushed specimens injected with colored latex. CONCLUSION: For better-quality specimens for neurosurgical education and training, formalin preservation within ≤72 h of death was preferable, as was injection with colored latex. Formalin-flushed specimens more closely resembled live brain parenchyma. Assessment scores were lower for preparation techniques performed > 72 h postmortem and for nonformalin preservation solutions. The positive correlation between cadaver assessment scores and our novel MRI score indicates that donation organizations and institutional buyers should incorporate MRI as a screening tool for the selection of high-quality specimens.

Quantification of motion during microvascular anastomosis simulation using machine learning hand detection.

OBJECTIVE: Microanastomosis is one of the most technically demanding and important microsurgical skills for a neurosurgeon. A hand motion detector based on machine learning tracking technology was developed and implemented for performance assessment during microvascular anastomosis simulation. METHODS: A microanastomosis motion detector was developed using a machine learning model capable of tracking 21 hand landmarks without physical sensors attached to a surgeon's hands. Anastomosis procedures were simulated using synthetic vessels, and hand motion was recorded with a microscope and external camera. Time series analysis was performed to quantify the economy, amplitude, and flow of motion using data science algorithms. Six operators with various levels of technical expertise (2 experts, 2 intermediates, and 2 novices) were compared. RESULTS: The detector recorded a mean (SD) of 27.6 (1.8) measurements per landmark per second with a 10% mean loss of tracking for both hands. During 600 seconds of simulation, the 4 nonexperts performed 26 bites in total, with a combined excess of motion of 14.3 (15.5) seconds per bite, whereas the 2 experts performed 33 bites (18 and 15 bites) with a mean (SD) combined excess of motion of 2.8 (2.3) seconds per bite for the dominant hand. In 180 seconds, the experts performed 13 bites, with mean (SD) latencies of 22.2 (4.4) and 23.4 (10.1) seconds, whereas the 2 intermediate operators performed a total of 9 bites with mean (SD) latencies of 31.5 (7.1) and 34.4 (22.1) seconds per bite. CONCLUSIONS: A hand motion detector based on machine learning technology allows the identification of gross and fine movements performed during microanastomosis. Economy, amplitude, and flow of motion were measured using time series data analysis. Technical expertise could be inferred from such quantitative performance analysis.

Modified Puerto Rico Recurrence Scale for chronic subdural hematomas: augmenting the grading scale with postoperative pneumocephalus volume.

BACKGROUND: Chronic subdural hematomas (CSDHs) are common in the elderly, with a relatively high rate of recurrence after initial surgical intervention. Our research team previously created a predictive grading system, the Puerto Rico Recurrence Scale (PRRS), to identify patients at high risk of CSDH recurrence. In this study, we introduce a modification of the (mPRRS) that includes pneumocephalus volume, which has been independently associated with recurrence. METHODS: A single-center Puerto Rican population-based retrospective study was performed to analyze data for patients treated for CSDH at 1 institution between July 1, 2017, and December 31, 2019. Univariate and multivariate analyses were used to create a grading scale predictive of recurrence. Retrospective validation was conducted for the cohort. RESULTS: Of 108 patients included in the study, 42 had recurrence, and 66 had nonrecurrence. Postoperative subdural space, postoperative midline shift, and pneumocephalus volume were all higher with recurrence (P = 0.002, P = 0.009, and P < 0.001, respectively). Multivariate analysis was used to create a 6-point grading scale comprising 3 variables (pneumocephalus volume [< 10, 10-20, 21-30, and > 30 cm3], postoperative midline shift [< 0.4, 0.41-1.0, and > 1.0 cm], and laterality [unilateral and bilateral]). Recurrence rates progressively increased in low-risk to high-risk groups (2/18 [11%] vs 21/34 [62%]; P < 0.003). CONCLUSION: The mPRRS incorporating pneumocephalus measurement improves CSDH recurrence prediction. The mPRRS indicated that patients with higher scores have a greater risk of recurrence and emphasized the importance of measuring postoperative variables for prediction. The mPRRS grading scale for CSDHs may be applicable not only to the Puerto Rican population but also to the general population.

Primary and metastatic paraganglioma of the cranial vault.

AIM: Primary paragangliomas (PGs) are extra-adrenal neuroendocrine tumours that are extremely rare. Multiple lesions in the central nervous system raise suspicion of a metastatic process. Lack of consensus on their management warrants the categorization of existing literature to evaluate management options. METHODS: A systematic review of the medical literature on paraganglioma within the cranial vault was completed in accordance with PRISMA guidelines using the Medline database. Tumour physical measures, management parameters, and immunohistochemistry of all documented cases of primary and secondary paraganglioma within the cranial vault were descriptively compared. This review was augmented by comparison with our centre's case of a 48-year-old man diagnosed with metastatic PG originating in the cauda equina and seeding in the cerebellum. Histological parameters within the literature was also established. RESULTS: The systematic literature review yielded published 52 papers. Most prevalent primary intracranial PGs (n = 37) were in the sellar region (78%, n = 23) and the cerebellum (21%, n = 6). The highest progression free survival was seen in primary sellar PGs (87.5% by 34.5 months) and cerebellar PGs (100% by 35.7 months) when treated with adjuvant radiotherapy with subtotal resection or gross total resection, respectively. Contrasting, the most frequent intracranial PGs metastases (n = 15) occurred in the cerebellum (36%, n = 6), and the cerebral parenchyma (29%, n = 4). Their recurrence rate was between 4 and 10% and these metastasized PG in the cerebellum are slow growing (8.9 years, range: 3-22 years). Adjuvant radiotherapy with Gross Total Resection resulted in the optimum progression-free survival (100% up to 48 months) for the patient with PGs metastasis to the cerebellum. CONCLUSION: Metastatic PGs tend to be slow-growing and are clinically silent tumours. Diagnosed patients should undergo regular surveillance neuroradiological assessment, regardless of symptomatology, for metastases along the complete neural axis. We recommend operative management with GTR and adjunct RT in these patients.

Toward "bigger" data for neurosurgical anatomical research: a single centralized quantitative neurosurgical anatomy platform.

Quantitative neurosurgical anatomy research aims to produce surgically applicable knowledge for improving operative decision-making using measurements from anatomical dissection and tools such as stereotaxis. Although such studies attempt to answer similar research questions, there is little standardization between them, offering minimal comparability. Modern technology has been incorporated into the research methodology, but many scientific principles are lacking, and results are not broadly applicable or suitable for evaluating big-data trends. Advances in information technology and the concept of big data permit more accessible and robust means of producing valuable, standardized, reliable research. A technology project, "Inchin," is presented to address these needs for neurosurgical anatomy research. This study applies the concept of big data to neurosurgical anatomy research, specifically in quantifying surgical metrics. A remote-hosted web application was developed for computing standard neurosurgical metrics and storing measurement data. An online portal (Inchin) was developed to produce a database to facilitate and promote neurosurgical anatomical research, applying optimal scientific methodology and big-data principles to this recent and evolving field of research. Individual data sets are not insignificant, but a collective of data sets present advantages. Large data sets allow confidence in data trends that are usually obscured in smaller numbers of samples. Inchin, a single centralized software platform, can act as a global database of results of neurosurgical anatomy studies. A calculation tool ensuring standardized peer-reviewed methodology, Inchin is applied to the analysis of neurosurgical metrics and may promote efficient study collaboration within and among neurosurgical laboratories.

Management of injuries on the 16th-century battlefield: Ambroise Paré's contributions to neurosurgery and functional recovery.

During the 1536 siege of Turin in northern Italy, a young French barber-surgeon abandoned the conventional treatment of battle-inflicted wounds, launching a revolution in military medicine and surgical techniques. Ambroise Paré (1510-1590) was born into a working-class Huguenot family in Laval, France, during an era when surgery was not considered a respectable profession. He rose from humble origins as a barber-surgeon, a low-ranked occupation in the French medical hierarchy, to become a royal surgeon (chirurgien ordinaire du Roi) serving 4 consecutive French monarchs. His innovative ideas and surgical practice were a response to the environment created by new military technology on 16th-century European battlefields. Gunpowder weapons caused unfamiliar, complicated injuries that challenged Paré to develop new techniques and surgical instruments. Although Paré's contributions to the treatment of wounds and functional prosthetics are documented, a deeper appreciation of his role in military neurosurgery is needed. This paper examines archives, primary texts, and written accounts by Paré that reveal specific patient cases highlighting his innovative contributions to neurotrauma and neurosurgery during demanding and harrowing circumstances, on and off the battlefield, in 16th-century France. Notably, trepanation indications increased because of battlefield head injuries, and Paré frequently described this technique and improved the design of the trepan tool. His contribution to neurologically related topics is extensive; there are more chapters devoted to the nervous system than to any other organ system in his compendium, Oeuvres. Regarding anatomical knowledge as fundamentally important and admiring the contemporary contributions of Andreas Vesalius, Paré reproduced many images from Vesalius' works at his own great expense. The manner in which Paré's participation in military expeditions enabled collaboration with multidisciplinary artisans on devices, including surgical tools and prosthetics, to restore neurologically associated functionality is also discussed. Deeply religious, in a life filled with adventure, and serving in often horrendous conditions during a time when Galenic dogma still dominated medical practice, Paré developed a reputation for logic, empiricism, technology, and careful treatment. "I have [had] the opportunity to praise God, for what he called me to do in medical operation, which is commonly called surgery, which could not be bought with gold or silver, but by only virtue and great experimentation."

Real-time intraoperative surgical telepathology using confocal laser endomicroscopy.

OBJECTIVE: Communication between neurosurgeons and pathologists is mandatory for intraoperative decision-making and optimization of resection, especially for invasive masses. Handheld confocal laser endomicroscopy (CLE) technology provides in vivo intraoperative visualization of tissue histoarchitecture at cellular resolution. The authors evaluated the feasibility of using an innovative surgical telepathology software platform (TSP) to establish real-time, on-the-fly remote communication between the neurosurgeon using CLE and the pathologist. METHODS: CLE and a TSP were integrated into the surgical workflow for 11 patients with brain masses (6 patients with gliomas, 3 with other primary tumors, 1 with metastasis, and 1 with reactive brain tissue). Neurosurgeons used CLE to generate video-flow images of the operative field that were displayed on monitors in the operating room. The pathologist simultaneously viewed video-flow CLE imaging using a digital tablet and communicated with the surgeon while physically located outside the operating room (1 pathologist was in another state, 4 were at home, and 6 were elsewhere in the hospital). Interpretations of the still CLE images and video-flow CLE imaging were compared with the findings on the corresponding frozen and permanent H&E histology sections. RESULTS: Overall, 24 optical biopsies were acquired with mean ± SD 2 ± 1 optical biopsies per case. The mean duration of CLE system use was 1 ± 0.3 minutes/case and 0.25 ± 0.23 seconds/optical biopsy. The first image with identifiable histopathological features was acquired within 6 ± 0.1 seconds. Frozen sections were processed within 23 ± 2.8 minutes, which was significantly longer than CLE usage (p < 0.001). Video-flow CLE was used to correctly interpret tissue histoarchitecture in 96% of optical biopsies, which was substantially higher than the accuracy of using still CLE images (63%) (p = 0.005). CONCLUSIONS: When CLE is employed in tandem with a TSP, neurosurgeons and pathologists can view and interpret CLE images remotely and in real time without the need to biopsy tissue. A TSP allowed neurosurgeons to receive real-time feedback on the optically interrogated tissue microstructure, thereby improving cross-functional communication and intraoperative decision-making and resulting in significant workflow advantages over the use of frozen section analysis.

Extradural anterior clinoidectomy versus endoscopic transplanum-transcavernous approach to the paraclinoid region: quantitative anatomical exposure analysis.

BACKGROUND: Transcranial anterior clinoidectomy is a conventional microsurgical approach for treatment of paraclinoid aneurysms. The endoscopic endonasal approach (EEA) is an alternative method for clipping intracranial aneurysms. No analysis has been conducted to anatomically compare approaches with respect to treating paraclinoid aneurysms. The surgical anatomical exposures of the paraclinoid region during transcranial extradural anterior clinoidectomy (EAC) and the endoscopic endonasal transplanum-cavernous approach (EETC) are described and quantitatively assessed. METHOD: Seven cadaveric heads underwent EAC and EETC. Measurements included the area of exposure, volume of surgical freedom, angle of attack, ophthalmic artery (OphA) origin, and coronal exposure angle of the internal carotid artery (ICA). RESULTS: The EETC provided a larger area of exposure than the EAC (100.1±24.9 vs 76.1±12.9 mm2, p = 0.04). The EAC provided a higher volume of surgical freedom and greater angle of attack than the EETC in all neurovascular parameters, including the OphA, superior hypophyseal artery (SHA), distal ICA, and distal dural ring (all p < 0.001). The OphA origin was intradural in 85.7% and extradural in 14.3% of specimens. With regard to the coronal angle of exposure, the EAC exposed the OphA and SHA in the upper lateral quadrant (67.9±7.8° and 80.6±4.5°, respectively) and the distal ICA in the upper medial and upper lateral quadrants (92±7.5°). The EEA exposed the OphA, SHA, and distal ICA in the upper medial and lower medial quadrants (130.4±10.7°, 68.4±10.8°, and 58±11.4°, respectively). CONCLUSIONS: The EAC and EETC each offer specific advantages for paraclinoid region exposure. The EAC is appropriate for paraclinoid aneurysms that occur at the dorsolateral surface of the paraclinoid ICA. The EETC is an alternative approach for aneurysms that occur along medial surface of the paraclinoid ICA (e.g., carotid cave and SHA aneurysms). The EETC provides greater surgical exposure to the medial aspect of the paraclinoid ICA.

A two-stage combined anterolateral and endoscopic endonasal approach to the petroclival region: an anatomical study and clinical application.

OBJECT: The pretemporal transcavernous anterior petrosal (PTAP) approach and the combined petrosal (CP) approach have been used to resect petroclival meningiomas (PCMs). In this cadaveric anatomical study, a two-stage combined PTAP and endoscopic endonasal far medial (EEFM) approach (the PTAPE approach) was compared morphometrically to the CP approach. A case study provides a clinical example of using the PTAPE approach to treat a patient with a PCM. The key elements of the approach selection process are outlined. METHODS: Five cadaveric specimens underwent a CP approach and 5 underwent a PTAPE approach. The area of drilled clivus, length of multiple cranial nerves (CNs), and the area of brain stem exposure were measured, reported as means (standard deviations) by group, and compared. RESULTS: The total area of the clivus drilled in the PTAPE group (695.3 [121.7] mm2) was greater than in the CP group (88.7 [17.06] mm2, P < 0.01). Longer segments of CN VI were exposed via the PTAPE than the CP approach (35.6 [9.07] vs. 16.3 [6.02] mm, P < 0.01). CN XII (8.8 [1.06] mm) was exposed only in the PTAPE group. Above the pontomedullary sulcus, the total area of brain stem exposed was greater with the PTAPE than the CP approach (1003.4 [219.5] mm2 vs. 437.6 [83.7] mm2, P < 0.01). Similarly, the total exposure of the medulla was greater after the PTAPE than the CP exposure (240.2 [57.06] mm2 vs. 48.1 [19.9] mm2, P < 0.01). CONCLUSION: A combined open-endoscopic paradigm is proposed for managing large PCMs. This approach incorporates the EEFM approach to address the limitations of the PTAP and the CP approach in a systematic fashion. Understanding the anatomical findings of this study will aid in tailoring surgical approaches to patients with these complex lesions.

Visualization of brain microvasculature and blood flow in vivo: Feasibility study using confocal laser endomicroscopy.

OBJECTIVE: Qualitative and quantitative analyses of blood flow in normal and pathologic brain and spinal cord microvasculature were performed using confocal laser endomicroscopy (CLE). METHODS: Blood flow in cortical, dural, and spinal cord microvasculature was assessed in vivo in swine. We assessed microvasculature under normal conditions and after vessel occlusion, brain injury due to cold or surgical trauma, and cardiac arrest. Tumor-associated microvasculature was assessed in vivo and ex vivo in 20 patients with gliomas. RESULTS: We observed erythrocyte flow in vessels 5-500 µm in diameter. Thrombosis, flow arrest and redistribution, flow velocity changes, agglutination, and cells rolling were assessed in normal and injured brain tissue. Microvasculature in in vivo CLE images of gliomas was classified as normal in 68% and abnormal in 32% of vessels on the basis of morphological appearance. Dural lymphatic channels were discriminated from blood vessels. Microvasculature CLE imaging was possible for up to 30 minutes after a 1 mg/kg intravenous dose of fluorescein. CONCLUSIONS: CLE imaging allows assessment of cerebral and tumor microvasculature and blood flow alterations with subcellular resolution intraoperative imaging demonstrating precise details of real-time cell movements. Research and clinical scenarios may benefit from this novel intraoperative in vivo microscopic fluorescence imaging modality.

Multiple and mirror intracranial aneurysms: study of prevalence and associated risk factors.

OBJECTIVE: Multiple intracranial aneurysms (MIA) account for 30% of all intracranial aneurysms, while mirror aneurysms, a subgroup of MIA, are present in 5% of all patients with cerebral aneurysms. We investigated the risk factors associated with the presence of multiple and mirror intracranial aneurysms. METHODS: 1404 patients, 314 males (22.4%) and 1090 female (77.6%) were enrolled for this study. Diagnosis was performed with a digital subtraction angiography (DSA). Multiplicity was defined as the presence of two or more aneurysms and mirror aneurysms as one pair of aneurysms involving bilateral corresponding arteries. Patients were followed-up from September 2009 till August 2018. Individuals' characteristics such as sex, age, smoking, hypertension and use of contraceptives were evaluated. RESULTS: Five hundred and twelve patients (36.4%) were diagnosed with MIA, approximately 4%/year. We observed 203 pairs of mirror aneurysms, accounting for 406 aneurysms (13% of the population). There was an increased frequency of females with multiple (p < 0.001, OR = 1.883, 95% CI = 1.386-2.560) and mirror aneurysms (p < 0.001, OR = 2.828, 95% CI = 1.725-4.636). Smoking was associated with multiplicity (p< 0.001, OR = 1.458, 95% CI = 1.160-1.833), as well as advanced age (p < 0.001, OR = 1.938, 95% CI = 1.438-2.611), but there was no significant relation with presence of mirror aneurysms. We observed higher frequency of baby aneurysms (<3mm) in the group of patients with MIA, while giant aneurysms (>25 mm) were most found in patients with only one aneurysm (p < 0.001). No differences between patients who used contraceptives against patients who did not use were found (p = 0.600). CONCLUSIONS: Gender and smoking, known risk factors to the development of a single intracranial aneurysm, are proportionally increased in patients with MIA. Hypertension and oral contraceptives were not associated with multiplicity.

Tailoring the surgical corridor to the basilar apex in the pretemporal transcavernous approach: morphometric analyses of different neurovascular mobilization maneuvers.

BACKGROUND: The pretemporal transcavernous approach (PTA) provides optimal exposure and access to the basilar artery (BA); however, the PTA can be invasive when vital neurovascular structures are mobilized. The goal of this study was to evaluate mobilization strategies to tailor approaches to the BA. METHODS: After an orbitozygomatic craniotomy, 10 sides of 5 cadaveric heads were used to assess the surgical access to the BA via the opticocarotid triangle (OCT), carotid-oculomotor triangle (COT), and oculomotor-tentorial triangle (OTT). Measurements were obtained, and morphometric analyses were performed for natural neurovascular positions and after each stepwise expansion maneuver. An imaginary line connecting the midpoints of the limbus sphenoidale and dorsum sellae was used as a reference to normalize the measurements of BA exposure and to facilitate the clinical applicability of this technique. RESULTS: In the OCT, the exposed BA segment ranged from - 1 ± 3.9 to + 6 ± 2.0 mm in length in its natural position. In the COT, the accessible BA segment ranged from - 4 ± 2.3 to - 2 ± 3.0 mm in length in its natural position. Via the OTT, the accessible BA segment ranged from - 7 ± 2.6 to - 5 ± 2.8 mm in length in its natural position. In the OCT, COT, and OTT, a posterior clinoidectomy extended the exposure down to - 6 ± 2.7, - 8 ± 2.5, and - 9 ± 2.9 mm, respectively. CONCLUSIONS: This study quantitatively evaluated the need for the expansion maneuvers in the PTA to reach BA aneurysms according to the patient's anatomical characteristics.

Posterior open-wedge anterior longitudinal ligament release: Cadaveric technique analysis.

Anterior column release is a powerful surgical technique for achieving spinopelvic balance in adult patients with sagittal plane deformities. We present an alternative strategy for focal deformity correction from a posterior-only approach. The purpose of this study was to evaluate the feasibility and efficacy of a novel surgical technique called posterior open-wedge diskectomy and anterior longitudinal ligament (ALL) release (POWAR). A cadaveric torso underwent POWARs at the L1-L4 intervertebral disc spaces. Baseline measurements of end-plate angle (EPA), anterior intervertebral disc height (ADH), and posterior intervertebral disc height (PDH) were obtained. These measurements were repeated after three stages of correction: posterior column compression alone, posterior column compression following Schwab grade 2 osteotomies, and posterior column compression following POWAR. A second cadaver underwent posterolateral spinal dissection to demonstrate the pertinent anatomical features relevant to this novel procedure. With each stage of correction, a sequential increase in EPA and ADH and a decrease in PDH were demonstrated. The large increase in ADH seen following POWAR confirmed successful release of the ALL. In situ investigation of the aorta and inferior vena cava following anterior exposure revealed no injury to the great vessels or surrounding structures. Ex vivo testing of the aorta and inferior vena cava took place at the L3-4 level. This testing demonstrated no injury or tears to either vessel. POWAR is a new surgical technique that can provide an alternative to three-column osteotomy for surgeons performing spinal reconstructions in adults through an open, posterior-only approach. Clin. Anat. 32:348-353, 2019. © 2018 Wiley Periodicals, Inc.

Anatomical assessment of the digastric branch of the facial nerve as a landmark to localize the extratemporal facial nerve trunk.

PURPOSE: Localization of the facial nerve trunk (FNT) [i.e., the portion of the facial nerve between the stylomastoid foramen (SMF) and pes anserinus] may be required during various surgical interventions such as parotidectomy and hypoglossal-facial anastomosis. Several landmarks have been proposed for efficient identification of the FNT. We sought to assess the anatomical features of the digastric branch of the facial nerve (DBFN) and its potential as a landmark to identify FNT. METHODS: Fifteen sides of eight cadaveric heads were dissected to find the DBFN. Anatomic features of DBFN including its point of origin relative to SMF, length, and important relationships, as well as the distance between the insertion point on the digastric muscle and mastoid tip were recorded. RESULTS: DBFN was found in all specimens originating from the FNT outside the SMF with an average length (± standard deviation) of 15.4 ± 3.4 mm. In all specimens, the DBFN inserted on the superomedial aspect of the posterior belly of the digastric muscle (PBD). In 8/15 specimens, DBFN was accompanied by the stylomastoid artery on its anteromedial side. Average distance (± standard deviation) between the mastoid tip and the nerve insertion point on PBD was 13.6 ± 2.0 mm (range 10-17). CONCLUSIONS: The DBFN is a reliable landmark for identifying the FNT. It could be consistently identified within 15-20 mm of the mastoid tip on the superomedial aspect of the PBD. The DBFN may be used as a supplementary landmark for efficient localization of the FNT. LEVEL OF EVIDENCE: Not applicable (anatomic study).

Improving the utility of 1H-MRS for the differentiation of glioma recurrence from radiation necrosis.

Proton magnetic resonance spectroscopy (1H-MRS) has shown promise in distinguishing recurrent high-grade glioma from posttreatment radiation effect (PTRE). The purpose of this study was to establish objective 1H-MRS criteria based on metabolite peak height ratios to distinguish recurrent tumor (RT) from PTRE. A retrospective analysis of magnetic resonance imaging and 1H-MRS data was performed. Spectral metabolites analyzed included N-acetylaspartate, choline (Cho), creatine (Cr), lactate (Lac), and lipids (Lip). Quantitative 1H-MRS criteria to differentiate RT from PTRE were identified using 81 biopsy-matched spectral voxels. A receiver operating characteristic curve analysis was conducted for all metabolite ratio combinations with the pathology diagnosis as the classification variable. Forward discriminant analysis was used to identify ratio variables that maximized the correct classification of RT versus PTRE. Our results were applied to 205 records without biopsy-matched voxels to examine the percent agreement between our criteria and the radiologic diagnoses. Five ratios achieved an acceptable balance [area under the curve (AUC) ≥ 0.700] between sensitivity and specificity for distinguishing RT from PTRE, and each ratio defined a criterion for diagnosing RT. The ratios are as follows: Cho/Cr > 1.54 (sensitivity 66%, specificity 79%), Cr/Cho ≤ 0.63 (sensitivity 65%, specificity 79%), Lac/Cho ≤ 2.67 (sensitivity 85%, specificity 58%), Lac/Lip ≤ 1.64 (sensitivity 54%, specificity 95%), and Lip/Lac > 0.58 (sensitivity 56%, specificity 95%). Application of our ratio criteria in prospective studies may offer an alternative to biopsy or visual spectral pattern recognition to distinguish RT from PTRE in patients with gliomas.

Chen Jingrun, China's famous mathematician: devastated by brain injuries on the doorstep to solving a fundamental mathematical puzzle.

Chen Jingrun (1933-1996), perhaps the most prodigious mathematician of his time, focused on the field of analytical number theory. His work on Waring's problem, Legendre's conjecture, and Goldbach's conjecture led to progress in analytical number theory in the form of "Chen's Theorem," which he published in 1966 and 1973. His early life was ravaged by the Second Sino-Japanese War and the Chinese Cultural Revolution. On the verge of solving Goldbach's conjecture in 1984, Chen was struck by a bicyclist while also bicycling and suffered severe brain trauma. During his hospitalization, he was also found to have Parkinson's disease. Chen suffered another serious brain concussion after a fall only a few months after recovering from the bicycle crash. With significant deficits, he remained hospitalized for several years without making progress while receiving modern Western medical therapies. In 1988 traditional Chinese medicine experts were called in to assist with his treatment. After a year of acupuncture and oxygen therapy, Chen could control his basic bowel and bladder functions, he could walk slowly, and his swallowing and speech improved. When Chen was unable to produce complex work or finish his final work on Goldbach's conjecture, his mathematical pursuits were taken up vigorously by his dedicated students. He was able to publish Youth Math, a mathematics book that became an inspiration in Chinese education. Although he died in 1996 at the age of 63 after surviving brutal political repression, being deprived of neurological function at the very peak of his genius, and having to be supported by his wife, Chen ironically became a symbol of dedication, perseverance, and motivation to his students and associates, to Chinese youth, to a nation, and to mathematicians and scientists worldwide.

Monsters and the case of L. Joseph: André Feil's thesis on the origin of the Klippel-Feil syndrome and a social transformation of medicine.

André Feil (1884-1955) was a French physician best recognized for his description, coauthored with Maurice Klippel, of patients with congenital fusion of cervical vertebrae, a condition currently known as Klippel-Feil syndrome. However, little is known about his background aside from the fact that he was a student of Klippel and a physician who took a keen interest in describing congenital anomalies. Despite the relative lack of information on Feil, his contributions to the fields of spinal disease and teratology extended far beyond science to play an integral role in changing the misguided perception shrouding patients with disfigurements, defects, deformities, and so-called monstrous births. In particular, Feil's 1919 medical school thesis on cervical abnormalities was a critical publication in defying long-held theory and opinion that human "monstrosities," anomalies, developmental abnormalities, and altered congenital physicality were a consequence of sinful behavior or a reversion to a primitive state. Indeed, his thesis on a spinal deformity centering on his patient, L. Joseph, was at the vanguard for a new view of a patient as nothing less than fully human, no matter his or her physicality or appearance.

Prospective evaluation of the utility of intraoperative confocal laser endomicroscopy in patients with brain neoplasms using fluorescein sodium: experience with 74 cases.

OBJECTIVE: This study evaluated the utility, specificity, and sensitivity of intraoperative confocal laser endomicroscopy (CLE) to provide diagnostic information during resection of human brain tumors. METHODS: CLE imaging was used in the resection of intracranial neoplasms in 74 consecutive patients (31 male; mean age 47.5 years; sequential 10-month study period). Intraoperative in vivo and ex vivo CLE was performed after intravenous injection of fluorescein sodium (FNa). Tissue samples from CLE imaging-matched areas were acquired for comparison with routine histological analysis (frozen and permanent sections). CLE images were classified as diagnostic or nondiagnostic. The specificities and sensitivities of CLE and frozen sections for gliomas and meningiomas were calculated using permanent histological sections as the standard. RESULTS: CLE images were obtained for each patient. The mean duration of intraoperative CLE system use was 15.7 minutes (range 3-73 minutes). A total of 20,734 CLE images were correlated with 267 biopsy specimens (mean number of images/biopsy location, in vivo 84, ex vivo 70). CLE images were diagnostic for 45.98% in vivo and 52.97% ex vivo specimens. After initiation of CLE, an average of 14 in vivo images and 7 ex vivo images were acquired before identification of a first diagnostic image. CLE specificity and sensitivity were, respectively, 94% and 91% for gliomas and 93% and 97% for meningiomas. CONCLUSIONS: CLE with FNa provided intraoperative histological information during brain tumor removal. Specificities and sensitivities of CLE for gliomas and meningiomas were comparable to those for frozen sections. These data suggest that CLE could allow the interactive identification of tumor areas, substantially improving intraoperative decisions during the resection of brain tumors.