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Jacques J. Morcos

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Lillian B. Boettcher, Phillip A. Bonney, Adam D. Smitherman, and Michael E. Sughrue

Of the multitude of medical and psychiatric conditions ascribed to Hitler both in his lifetime and since his suicide in April 1945, few are more substantiated than parkinsonism. While the timeline of the development of this condition, as well as its etiology, are debated, there is clear evidence for classic manifestations of the disease, most prominently a resting tremor but also stooped posture, bradykinesia, micrographia, and masked facial expressions, with progression steadily seen over his final years. Though ultimately speculation, some have suggested that Hitler suffered from progressive cognitive and mood disturbances, possibly due to parkinsonism, that affected the course of events in the war. Here, the authors discuss Hitler’s parkinsonism in the context of the Third Reich and its eventual destruction, maintaining that ultimately his disease had little effect on the end result.

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Anujan Poologaindran, Stephen R. Lowe, and Michael E. Sughrue

Connectomics is the production and study of detailed “connection” maps within the nervous system. With unprecedented advances in imaging and high-performance computing, the construction of individualized connectomes for routine neurosurgical use is on the horizon. Multiple projects, including the Human Connectome Project (HCP), have unraveled new and exciting data describing the functional and structural connectivity of the brain. However, the abstraction from much of these data to clinical relevance remains elusive. In the context of preserving neurological function after supratentorial surgery, abstracting surgically salient points from the vast computational data in connectomics is of paramount importance. Herein, the authors discuss four interesting observations from the HCP data that have surgical relevance, with an emphasis on the cortical organization of language: 1) the existence of a motor speech area outside of Broca’s area, 2) the eloquence of the frontal aslant tract, 3) the explanation of the medial frontal cognitive control networks, and 4) the establishment of the second ventral stream of language processing. From these connectome observations, the authors discuss the anatomical basis of their insights as well as relevant clinical applications. Together, these observations provide a firm platform for neurosurgeons to advance their knowledge of the cortical networks involved in language and to ultimately improve surgical outcomes. It is hoped that this report encourages neurosurgeons to explore new vistas in connectome-based neurosurgery.

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Michael E. Sughrue, Michael W. McDermott, and Andrew T. Parsa

Clinical approaches to the surgical management of optic chiasm compression stress quick action, as several case series have demonstrated minimal vision restoration following aggressive decompression in patients presenting more than 3 days after the onset of blindness. The authors here report the case of a 48-year-old woman who presented with near-complete binocular vision loss but regained visual function following surgical removal of a giant planum-tuberculum meningioma, which was performed 8 days after a documented loss in light perception. The interval between the patient's vision loss and successful vision-restoring decompressive surgery is the longest recorded to date in the literature. This case shows the importance of aggressive decompression of mass lesions despite extended intervals of optic nerve dysfunction.

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Nader Sanai, Michael E. Sughrue, Gopal Shangari, Kenny Chung, Mitchel S. Berger, and Michael W. McDermott

Object

Although meningiomas are commonly found along the supratentorial convexity, the risk profile associated with this subset of lesions in the modern neurosurgical era is unknown.

Methods

The authors retrospectively reviewed the clinical course of patients with supratentorial convexity meningiomas treated during the past 10 years. All patients had undergone MR imaging within 72 hours after surgery and at least 1 year of clinical follow-up. Patients with multiple meningiomas, hemangiopericytomas, malignant meningiomas, or tumor-prone syndromes were excluded from analysis.

Results

Between 1997 and 2007, 141 consecutive patients (median age 48 years, range 18–95 years) underwent resection of a supratentorial convexity meningioma. The most common signs or symptoms at presentation were headache (48%), seizures (34%), and weakness (21%). The mean tumor volume was 146.3 cm3 (range 1–512 cm3). There were no intraoperative complications or deaths. Medical or neurosurgical morbidity was noted in the postoperative course of 14 patients, equating to a 10% overall complication rate. Postoperative surgical complications included hematoma requiring evacuation, CSF leakage, and operative site infection. Medical complications included pulmonary embolus and deep vein thrombosis requiring treatment. A Simpson Grade 0 or 1 resection was achieved in 122 patients (87%). One hundred six tumors (75%) were WHO Grade I, whereas 35 (25%) were WHO Grade II. The median clinical follow-up was 2.9 years (range 1–10 years), and the median radiographic follow-up was 3.7 years (range 1–10 years). Six patients (4%) had radiographic evidence of tumor recurrence, with 3 (2%) undergoing repeat resection.

Conclusions

With the conservative recommendations for surgery for asymptomatic meningiomas and the advent of radiosurgery during the past 10 years, microsurgically treated convexity meningiomas are now typically large in size. Nevertheless, the patient's clinical course following microsurgical removal of these lesions is expected to be uncomplicated. The authors' findings provide a defined risk profile associated with the resection of supratentorial convexity meningiomas in the modern neurosurgical era.

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Michael E. Sughrue, Tyson Sheean, Phillip A. Bonney, Adrian J. Maurer, and Charles Teo

OBJECT

The relative benefit of repeat surgery for recurrent glioblastoma is unclear, in part due to the very heterogeneous nature of the patient population and the effect of clinician philosophy on the duration and aggressiveness of treatment. The authors sought to investigate the role of time to last recurrence on patient outcomes following aggressive repeat surgery for recurrent glioblastoma.

METHODS

The authors present outcomes in 104 patients undergoing repeat surgery for focally recurrent glioblastoma with at least 95% resection and adjuvant treatment at most recent prior surgery. In addition to common variables, they provide data regarding the period of progression-free survival (PFS) following an aggressive lesionectomy for focally recurrent primary glioblastoma (T2) and the time the tumor took to recur since the previous surgery (T1). They term the ratio T1/T2 the relative aggressivity index (RAI).

RESULTS

The median PFS was 7.8 months, 6.0 months, and 4.8 months following the second, third, and fourth–sixth craniotomies, respectively. Importantly, there was a wide range of outcomes, with time to postoperative recurrence ranging from 1 to 24 months in this group. Analysis showed no meaningful relationship between T1 and T2, meaning that previous PFS is entirely unable to predict the PFS that another surgery will provide the patient.

CONCLUSIONS

Repeat surgery for glioblastoma is beneficial in many cases, however this is hard to predict preoperatively. Often, surgery can provide the patient with a good period of disease freedom, but this is variable and in general it is not possible to reliably predict who these patients are.

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Christen M. O’Neal, Cordell M. Baker, Chad A. Glenn, Andrew K. Conner, and Michael E. Sughrue

The history of psychosurgery is filled with tales of researchers pushing the boundaries of science and ethics. These stories often create a dark historical framework for some of the most important medical and surgical advancements. Dr. Robert G. Heath, a board-certified neurologist, psychiatrist, and psychoanalyst, holds a debated position within this framework and is most notably remembered for his research on schizophrenia. Dr. Heath was one of the first physicians to implant electrodes in deep cortical structures as a psychosurgical intervention. He used electrical stimulation in an attempt to cure patients with schizophrenia and as a method of conversion therapy in a homosexual man. This research was highly controversial, even prior to the implementation of current ethics standards for clinical research and often goes unmentioned within the historical narrative of deep brain stimulation (DBS). While distinction between the modern practice of DBS and its controversial origins is necessary, it is important to examine Dr. Heath’s work as it allows for reflection on current neurosurgical practices and questioning the ethical implication of these advancements.

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Isaac Yang, Seunggu J. Han, Michael E. Sughrue, Tarik Tihan, and Andrew T. Parsa

Object

The tumor microenvironment in astrocytomas is composed of a variety of cell types, including infiltrative inflammatory cells that are dynamic in nature, potentially reflecting tumor biology. In this paper the authors demonstrate that characterization of the intratumoral inflammatory infiltrate can distinguish high-grade glioblastoma from low-grade pilocytic astrocytoma.

Methods

Tumor specimens from ninety-one patients with either glioblastoma or pilocytic astrocytoma were analyzed at the University of California, San Francisco. A systematic neuropathology analysis was performed. All tissue was collected at the time of the initial surgery prior to adjuvant treatment. Immune cell infiltrate not associated with necrosis or hemorrhage was analyzed on serial 4-μm sections. Analysis was performed for 10 consecutive hpfs and in 3 separate regions (total 30 × 0.237 mm2). Using immunohistochemistry for markers of infiltrating cytotoxic T cells (CD8), natural killer cells (CD56), and macrophages (CD68), the inflammatory infiltrates in these tumors were graded quantitatively and classified based on microanatomical location (perivascular vs intratumoral). Control markers included CD3, CD20, and human leukocyte antigen.

Results

Glioblastomas exhibited significantly higher perivascular (CD8) T-cell infiltration than pilocytic astrocytomas (62% vs 29%, p = 0.0005). Perivascular (49%) and intratumoral (89%; p = 0.004) CD56-positive cells were more commonly associated with glioblastoma. The CD68-positive cells also were more prevalent in the perivascular and intratumoral space in glioblastoma. In the intratumoral space, all glioblastomas exhibited CD68-positive cells compared with 86% of pilocytic astrocytomas (p = 0.0014). Perivascularly, CD68-positive infiltrate was also more prevalent in glioblastoma when compared with pilocytic astrocytoma (97% vs 86%, respectively; p = 0.0003). The CD3-positive, CD20-positive, and human leukocyte antigen-positive infiltrates did not differ between glioblastoma and pilocytic astrocytoma.

Conclusions

This analysis suggests a significantly distinct immune profile in the microenvironment of high-grade glioblastoma versus low-grade pilocytic astrocytoma. This difference in tumor microenvironment may reflect an important difference in the tumor biology of glioblastoma.

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Michael E. Ivan, Michael E. Sughrue, Aaron J. Clark, Ari J. Kane, Derick Aranda, Igor J. Barani, and Andrew T. Parsa

Object

Because of the rarity of glomus jugulare tumors, a variety of treatment paradigms are currently used. There is no consensus regarding the optimal management to control tumor burden while minimizing treatment-related morbidity. In this study, the authors assessed data collected from 869 patients with glomus jugulare tumors from the published literature to identify treatment variables that impacted clinical outcomes and tumor control rates.

Methods

A comprehensive search of the English-language literature identified 109 studies that collectively described outcomes for patients with glomus jugulare tumors. Univariate comparisons of demographic information between treatment cohorts were performed to detect differences in the sex distribution, age, and Fisch class of tumors among various treatment modalities. Meta-analyses were performed on calculated rates of recurrence and cranial neuropathy after subtotal resection (STR), gross-total resection (GTR), STR with adjuvant postoperative radiosurgery (STR+SRS), and stereotactic radiosurgery alone (SRS).

Results

The authors identified 869 patients who met their inclusion criteria. In these studies, the length of follow-up ranged from 6 to 256 months. Patients treated with STR were observed for 72 ± 7.9 months and had a tumor control rate of 69% (95% CI 57%–82%). Those who underwent GTR had a follow-up of 88 ± 5.0 months and a tumor control rate of 86% (95% CI 81%–91%). Those treated with STR+SRS were observed for 96 ± 4.4 months and had a tumor control rate of 71% (95% CI 53%–83%). Patients undergoing SRS alone had a follow-up of 71 ± 4.9 months and a tumor control rate of 95% (95% CI 92%–99%). The authors' analysis found that patients undergoing SRS had the lowest rates of recurrence of these 4 cohorts, and therefore, these patients experienced the most favorable rates of tumor control (p < 0.01). Patients who underwent GTR sustained worse rates of cranial nerve (CN) deficits with regard to CNs IX–XI than those who underwent SRS alone; however, the rates of CN XII deficits were comparable.

Conclusions

The authors' analysis is limited by the quality and accuracy of these studies and may reflect source study biases, as it is impossible to control for the quality of the data reported in the literature. Finally, due to the diverse range of data presentation, the authors found that they were limited in their ability to study and control for certain variables. Some of these limitations should be minimized with their use of meta-analysis methods, which statistically evaluate and adjust for between-study heterogeneity. These results provide the impetus to initiate a prospective study, appropriately controlling for variables that can confound the retrospective analyses that largely comprise the existing literature.

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Michael E. Sughrue, Martin J. Rutkowski, Derick Aranda, Igor J. Barani, Michael W. McDermott, and Andrew T. Parsa

Object

Definitive data allowing clinicians to predict which meningioma patients will fail to respond to conservative management are lacking. To address this need, the authors systematically reviewed the published literature regarding the natural history of small, untreated meningiomas.

Methods

The authors performed a systematic review of the existing literature on untreated meningiomas that were followed with serial MR imaging. They summarize the published linear rates of tumor growth, and the risk factors for development of new or worsened symptoms during follow-up by using a stratified chi-square test.

Results

The search methods identified 22 published studies reporting on 675 patients with untreated meningiomas followed by serial MR imaging. Linear growth rates varied significantly: no growth was the most common rate, although reports of more aggressive tumors noted growth rates of up to a 93% linear increase in size per year. The authors found that few patients with initial tumor diameters < 2 cm went on to develop new or worsened symptoms over a median follow-up period of 4.6 years. Patients with initial tumor diameters of 2–2.5 cm demonstrated a marked difference in the rate of symptom progression if their tumors grew > 10% per year, compared with those tumors growing ≤ 10% per year (42% vs 0%; p < 0.001, chi-square test). Patients with tumors between > 2.5 and 3 cm in initial size went on to develop new or worsened symptoms 17% of the time.

Conclusions

This systematic review of the literature regarding the clinical behavior of untreated meningiomas suggests that most meningiomas ≤ 2.5 cm in diameter do not proceed to cause symptoms in the approximately 5-year period following their discovery. Those that do cause symptoms can usually be predicted with close radiographic follow-up. Based on these findings, the authors suggest the importance of observation in the early course of treatment for small asymptomatic meningiomas, especially those with an initial diameter < 2 cm.