An unexpected role for the classical complement cascade in the elimination of central nervous system (CNS) synapses has recently been discovered. Complement proteins are localized to developing CNS synapses during periods of active synapse elimination and are required for normal brain wiring. The function of complement proteins in the brain appears analogous to their function in the immune system: clearance of cellular material that has been tagged for elimination. Similarly, synapses tagged with complement proteins may be eliminated by microglial cells expressing complement receptors. In addition, developing astrocytes release signals that induce the expression of complement components in the CNS. In the mature brain, early synapse loss is a hallmark of several neurodegenerative diseases. Complement proteins are profoundly upregulated in many CNS diseases prior to signs of neuron loss, suggesting a reactivation of similar developmental mechanisms of complementmediated synapse elimination potentially driving disease progression.

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The complement system: an unexpected role in synaptic pruning during development and disease.

The molecular basis of retinal ganglion cell death in glaucoma.

Objective. Sudden hearing loss (SHL) is a frightening symptom that often prompts an urgent or emergent visit to a physician. This guideline provides evidence-based recommendations for the diagnosis...

/pdf/clinical-practice-guideline-sudden-hearing-loss-8acwe9fo8a.pdf

Clinical practice guideline: sudden hearing loss.

Although meningiomas are the most common intracranial tumours, the level of evidence to provide recommendations for the diagnosis and treatment of meningiomas is low compared with other tumours such as high-grade gliomas. The meningioma task force of the European Association of Neuro-Oncology (EANO) assessed the scientific literature and composed a framework of the best possible evidence-based recommendations for health professionals. The provisional diagnosis of meningioma is mainly made by MRI. Definitive diagnosis, including histological classification, grading, and molecular profiling, requires a surgical procedure to obtain tumour tissue. Therefore, in many elderly patients, observation is the best therapeutic option. If therapy is deemed necessary, the standard treatment is gross total surgical resection including the involved dura. As an alternative, radiosurgery can be done for small tumours, or fractionated radiotherapy in large or previously treated tumours. Treatment concepts combining surgery and radiosurgery or fractionated radiotherapy, which enable treatment of the complete tumour volume with low morbidity, are being developed. Pharmacotherapy for meningiomas has remained largely experimental. However, antiangiogenic drugs, peptide receptor radionuclide therapy, and targeted agents are promising candidates for future pharmacological approaches to treat refractory meningiomas across all WHO grades.

/pdf/eano-guidelines-for-the-diagnosis-and-treatment-of-5gu77627p6.pdf

EANO guidelines for the diagnosis and treatment of meningiomas

Cancer of the breast

Object In 1957, Simpson published a seminal paper defining the risk factors for recurrence following surgical treatment of intracranial meningiomas. Given that Simpson's study was published more than 50 years ago, preceding image guidance technology and MR imaging, the authors reviewed their own experience with surgical treatment of Grade I meningiomas to determine if Simpson's grading scale is still relevant to modern neurosurgical practice. Methods From this cohort, the authors evaluated all patients undergoing craniotomy for resection of a histologically proven WHO Grade I meningioma as their initial therapy. Clinical information was retrospectively reconstructed using patient medical records and radiological data. Recurrence analysis was performed using the Kaplan-Meier method. Results The 5-year recurrence/progression-free survival for all patients receiving a Simpson Grade I, II, III, or IV resection was 95, 85, 88, and 81%, respectively (p = not significant, log-rank test). Kaplan-Meier analysis re...

The relevance of Simpson Grade I and II resection in modern neurosurgical treatment of World Health Organization Grade I meningiomas.

Despite significant research on the role of inflammation and immunosurveillance in the immunologic microenvironment of tumors, little attention has been given to the oncogenic capabilities of the complement cascade. The recent finding that complement may contribute to tumor growth suggests an insidious relationship between complement and cancer, especially in light of evidence that complement facilitates cellular proliferation and regeneration. We address the hypothesis that complement proteins promote carcinogenesis and suggest mechanisms by which complement can drive the fundamental features of cancer. Evidence shows that this diverse family of innate immune proteins facilitates dysregulation of mitogenic signaling pathways, sustained cellular proliferation, angiogenesis, insensitivity to apoptosis, invasion and migration, and escape from immunosurveillance. Given that the traditionally held functions for the complement system include innate immunity and cancer defense, our review suggests a new way of thinking about the role of complement proteins in neoplasia.

https://mcr.aacrjournals.org/content/molcanres/8/11/1453.full.pdf

Cancer and the complement cascade

BACKGROUND:

Grade II and III meningiomas have higher rates of tumor recurrence than grade I meningiomas after surgery and/or external irradiation. As the utility of noninvasive treatments for brain tumors increases, it is becoming increasingly important to assess the likelihood that a tumor is not benign before treatment initiation. Hence, the authors have reviewed a large series of their patients to determine risk factors for higher-grade pathology, with particular interest paid to tumor location.



METHODS:

The authors reviewed 378 patients presenting at their institution from 2000 to 2007 with histologically confirmed meningioma, central pathology grading according to the World Health Organization 2000 guidelines, and tumor location confirmed with preoperative imaging. They performed univariate and multivariate logistic regression on potential risk factors for high-grade pathology.



RESULTS:

Risk factors for grade II/III pathology included nonskull base location (2-fold) and male sex (2-fold). Patients with prior surgery had a 3-fold increased incidence of higher-grade meningiomas at presentation at the authors' center. The authors controlled for this referral bias by performing a multivariate regression, and analysis without patients receiving prior treatment. Ninety-seven percent of operations were performed for tumor size and clinical symptoms, whereas <3% were performed for interval growth or features concerning higher-grade pathology.



CONCLUSIONS:

Nonskull-base meningiomas, male sex, and prior surgery impart increased risk for grade II or III pathology. This increased risk translates to probable poorer prognosis and increased likelihood of recurrence after treatment. Thus, it is prudent to take these specific variables into consideration in conjunction with the complete clinical presentation when advising patients regarding their prognosis. Cancer 2011. © 2010 American Cancer Society.

Anatomic Location Is a Risk Factor for Atypical and Malignant Meningiomas

Recent evidence has demonstrated that the complement cascade is involved in a variety of physiologic and pathophysiologic processes in addition to its role as an immune effector. Research in a variety of organ systems has shown that complement proteins are direct participants in maintenance of cellular turnover, healing, proliferation and regeneration. As a physiologic housekeeper, complement proteins maintain tissue integrity in the absence of inflammation by disposing of cellular debris and waste, a process critical to the prevention of autoimmune disease. Developmentally, complement proteins influence pathways including hematopoietic stem cell engraftment, bone growth, and angiogenesis. They also provide a potent stimulus for cellular proliferation including regeneration of the limb and eye in animal models, and liver proliferation following injury. Here, we describe the complement cascade as a mediator of tissue growth and regeneration.

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The complement cascade as a mediator of tissue growth and regeneration

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+

Ari J. Kane

Papers

The relevance of Simpson Grade I and II resection in modern neurosurgical treatment of World Health Organization Grade I meningiomas.

Cancer and the complement cascade

Anatomic Location Is a Risk Factor for Atypical and Malignant Meningiomas

The complement cascade as a mediator of tissue growth and regeneration

A meta-analysis of tumor control rates and treatment-related morbidity for patients with glomus jugulare tumors.