The 20th Gray lecture 2019: health and heavy ions.

OBJECTIVE: Particle radiobiology has contributed new understanding of radiation safety and underlying mechanisms of action to radiation oncology for the treatment of cancer, and to planning of radiation protection for space travel. This manuscript will highlight the significance of precise physical and biologically effective dosimetry to this translational research for the benefit of human health.This review provides a brief snapshot of the evolving scientific basis for, and the complex current global status, and remaining challenges of hadron therapy for the treatment of cancer. The need for particle radiobiology for risk planning in return missions to the Moon, and exploratory deep-space missions to Mars and beyond are also discussed. METHODS: Key lessons learned are summarized from an impressive collective literature published by an international cadre of multidisciplinary experts in particle physics, radiation chemistry, medical physics of imaging and treatment planning, molecular, cellular, tissue radiobiology, biology of microgravity and other stressors, theoretical modeling of biophysical data, and clinical results with accelerator-produced particle beams. RESULTS: Research pioneers, many of whom were Nobel laureates, led the world in the discovery of ionizing radiations originating from the Earth and the Cosmos. Six radiation pioneers led the way to hadron therapy and the study of charged particles encountered in outer space travel. Worldwide about 250,000 patients have been treated for cancer, or other lesions such as arteriovenous malformations in the brain between 1954 and 2019 with charged particle radiotherapy, also known as hadron therapy. The majority of these patients (213,000) were treated with proton beams, but approximately 32,000 were treated with carbon ion radiotherapy. There are 3500 patients who have been treated with helium, pions, neon or other ions. There are currently 82 facilities operating to provide ion beam clinical treatments. Of these, only 13 facilities located in Asia and Europe are providing carbon ion beams for preclinical, clinical, and space research. There are also numerous particle physics accelerators worldwide capable of producing ion beams for research, but not currently focused on treating patients with ion beam therapy but are potentially available for preclinical and space research. Approximately, more than 550 individuals have traveled into Lower Earth Orbit (LEO) and beyond and returned to Earth. CONCLUSION: Charged particle therapy with controlled beams of protons and carbon ions have significantly impacted targeted cancer therapy, eradicated tumors while sparing normal tissue toxicities, and reduced human suffering. These modalities still require further optimization and technical refinements to reduce cost but should be made available to everyone in need worldwide. The exploration of our Universe in space travel poses the potential risk of exposure to uncontrolled charged particles. However, approaches to shield and provide countermeasures to these potential radiation hazards in LEO have allowed an amazing number of discoveries currently without significant life-threatening medical consequences. More basic research with components of the Galactic Cosmic Radiation field are still required to assure safety involving space radiations and combined stressors with microgravity for exploratory deep space travel. ADVANCES IN KNOWLEDGE: The collective knowledge garnered from the wealth of available published evidence obtained prior to particle radiation therapy, or to space flight, and the additional data gleaned from implementing both endeavors has provided many opportunities for heavy ions to promote human health.

The Natural History of Brain Arteriovenous Malformations

Brain arteriovenous malformations (AVMs) are relatively rare lesions with irreversible consequences in the context of hemorrhage. They are characterized by direct connections between arteries and veins without an intervening capillary network. The natural history of brain AVMs is controversial in the literature, with low evidence level gathered in the papers published, and with large divergence of results among them. A detailed understanding of the natural history is critical for treatment decision. The risk of development of deleterious outcomes such as hemorrhage or brain infarction should always be considered when submitting a patient to the risks of treatment. Several factors related to the patient and to the AVMs are determinants in the natural history of this disease. The topography, size, morphology and angioarchitecture of AVMs determine the risk of rupture. Large AVMs, those located in the posterior fossa and with deep venous drainage, have higher risk of rupture. Due to divergence in the literature regarding the natural history of AVMs, the choice of treatment should also consider experiences acquired over the years from reference centers with a high number of AVMs treated per year. We determined 7 variables that should be considered during the decision to treat an AVM: 1) previous hemorrhage; 2) aneurysm associated to the AVM; 3) direct arteriovenous fistula; 4) factors related to the nidus; 5) age and habits (smoking, sedentary lifestyle, diet quality); 6) the functional performance of the patient; 7) psychological factors.

Malformações arteriovenosas (MAVs) são lesões caracterizadas por conexões diretas entre artérias e veias sem rede capilar. São relativamente raras e com consequências muitas vezes irreversíveis no contexto de hemorragia. A história natural das MAVs é controversa na literatura, com pouca evidência extraída dos artigos publicados, além de alta divergência entre resultados. Um entendimento detalhado da história natural da doença é determinante para a decisão do tratamento. O risco de desenvolver consequências deletérias como hemorragia ou isquemia deve ser sempre considerado antes de submeter pacientes ao tratamento. Vários fatores relacionados ao paciente e às MAVs são determinantes na história natural da doença. A localização, tamanho, morfologia e angioarquitetura das MAVs estimam o risco de ruptura. As MAVs grandes, de fossa posterior, com drenagem venosa profunda, têm maior risco de ruptura. A decisão de tratar deve também levar em conta a experiência do serviço, adquirida após anos de tratamento de MAVs. Nós determinamos 7 fatores que devem ser avaliados diante da decisão de tratamento das MAVs: 1) hemorragia prévia; 2) aneurismas associados à MAV; 3) fístula arteriovenosa; 4) fatores relacionados ao nidus; 5) idade e hábitos de vida; 6) performance funcional do paciente; 7) fatores psicológicos.

Julius Caesar's Epilepsy: Was It Caused by A Brain Arteriovenous Malformation?

Julius Caesar (100-44 BC) was one of the most charismatic political figures in history. Best remembered for his military achievements, he was also a writer, historian, and statesman. Through his constitutional reforms, he played an important role in the events that led to the end of the Roman Republic and the birth of the Roman Empire. Historical sources reveal that Julius Caesar suffered from headaches, seizures, and personality changes. In this essay, we highlight the life of Julius Caesar, with emphasis on the potential origin of his sickness. Although a definitive diagnosis obviously cannot be made, as new published studies showed a possible cerebrovascular etiology, a new hypothetical diagnosis is presented.

Historical perspective of treatments of cranial arteriovenous malformations and dural arteriovenous fistulas.

Cerebral arteriovenous malformations and intracranial dural arteriovenous fistulas represent two important classes of intracranial vascular lesions. This article recalls the history on which current technical advances, including diagnoses, characterization, and treatment, is based. It also describes modern therapeutic options, including microsurgical, endovascular, and radiosurgery techniques.

Selected drake teachings: an affectionate look back and a look forward--the Charles G. Drake lecture: 2006.

The clinical neurosciences were blessed in the past century by the life and works of Dr. Charles Drake. The senior author (HHB) was honored to deliver the 2006 Charles Drake Lecture at the Annual Meeting of the Congress of Neurological Surgeons. Numerous colleagues in attendance requested that we prepare a written document reflecting the content of that presentation. In this article, we attempt to convey some of the primary teachings of Dr. Drake as he communicated them to his residents and fellows and to the international neuroscience audience through his hundreds of presentations and publications. We do our best to portray the unique style and humanism of this pioneer as he approached difficult diseases, critically ill patients, grieving families, and his trainees. Drake made major contributions to the knowledge of giant intracranial aneurysms, posterior circulation aneurysms, and intracranial arteriovenous malformations; we will focus on these topics. We dissect the principles he articulated and how they applied to his practice, look at how those ideas have influenced our contemporary thinking, and look to where we--as a discipline--may be going, having been leveraged by his enormous contributions. We attempt to articulate the unique perspectives "Charlie" provided with respect to how we learn our craft, integrity of reporting, and how we must progress into the future. It is our hope that this presentation brings to life for young neurosurgeons the unique character of Dr. Drake and his unprecedented blend of genius, creativity, technical skill, introspection, and ever-present humility.

Malformações arteriovenosas encefálicas: aspectos morfológicos, clínicos e operatórios. Revisão da literatura / Intracranial arteriovenous malformation. A literature review

É feita revisão da literatura sobre malformações arteriovenosas(MAV)encefálicas. MAV são anomalias morfológicas neurovasculares caracterizadas por comunicação direta entre artérias e veias , sem interposição do leito capilar, portanto sem resistência ao fluxo sanguíneo. Morfologicamente, MAV possuem três componentes distintos:aferências, nidus e eferências.As aferências incluem vasos originados de quaisquer artérias intra ou extracranianas que nutrem as MAV.O nidus corresponde a um enovelado complexo de artérias e veias anormais,unidas por uma ou mais fístulas além de calcificações e aneurismas intranidais. As eferências constituem as drenagens venosas, que podem ser superficial,profunda ou mista.Acidentes vasculares encefálicos(AVE)hemorrágicos são as manifestações mais comuns,ocorrendo em aproximadamente 50 por cento dos casos.O tratamento de MAV pode ser microcirurgia,embolização endovascular,radiocirúrgico estereotáxico,conservador ou multidisciplinar.Ressecção cirúrgica completa de MAV é considerada a melhor opção de tratamento,eliminando risco de futura hemorragia.Apesar do desenvolvimento tecnológico na área de neurocirurgia endovascular nas últimas décadas, a fisiopatologia de MAV e sua história natural ainda não estão bem esclarecidas.O tratamento representa um grande desafio.Acreditamos que estudos sobre complexidade arquitetônica e hemodinâmica de MAV são necessários a fim de estabelecer fatores de risco e prognósticos,melhorando os resultados do tratamento.

A proposed grading system for arteriovenous malformations. 1986.

An important factor in making a recommendation for treatment of a patient with arteriovenous malformation (AVM) is to estimate the risk of surgery for that patient. A simple, broadly applicable grading system that is designed to predict the risk of morbidity and mortality attending the operative treatment of specific AVM's is proposed. The lesion is graded on the basis of size, pattern of venous drainage, and neurological eloquence of adjacent brain. All AVM's fall into one of six grades. Grade I malformations are small, superficial, and located in non-eloquent cortex; Grade V lesions are large, deep, and situated in neurologically critical areas; and Grade VI lesions are essentially inoperable AVM's. Retrospective application of this grading scheme to a series of surgically excised AVM's has demonstrated its correlation with the incidence of postoperative neurological complications. The application of a standardized grading scheme will enable a comparison of results between various clinical series and between different treatment techniques, and will assist in the process of management decision-making.

Francesco Rizzoli (1809-1880) and the elusive case of Giulia: the description of an ''arteriovenous aneurysm passino through the wall of the skull''.

The improved knowledge of clinical and emodynamical aspects of extracranial arteriovenous malformations in the 18 th century provided a foundation for the understanding and treatment of cerebrovascular pathology. It was not until the late 19 th century that detailed clinicopathological reports of intracranial arteriovenous malformations were published. In this historical context, a seminal report written by the Italian surgeon Francesco Rizzoli is worthy of notice, the Giulia case. A 9-year-old girl presenting with seizures and an occipital pulsanting swelling was examined in 1873 by Rizzoli. He was able to use Giulia's signs and symptoms to predict the complex angioarchitecture of her ''arteriovenous aneurysm passing through the wall of skull''. The postmortem dissection completely confirmed the supposed diagnosis, disclosing a direct communication between the hypertrophic branches of the ocipital artery and the transverse sinus. The clinical course of that case is briefly reviewed in this article and the diagnosis of this unusual arteriovenous shunt is discussed in light of the current neurosurgical knowledge.

History of surgery for cerebrovascular disease in children. Part III. Arteriovenous malformations.

Arteriovenous malformations (AVMs) are the most common cause of intracerebral hemorrhage in children. In this paper the authors trace the historical evolution of the recognition, diagnosis, and treatment of pediatric intracerebral AVMs, and they summarize the contemporary approach and current controversies surrounding treatment of these lesions. Important distinctions between adult and pediatric AVMs are emphasized.

The evolution of endovascular treatment for intracranial arteriovenous malformations.

Endovascular therapy for arteriovenous malformations (AVMs) remains a relatively new approach. Beginning in the 1960s with the use of flow-directed techniques for selective embolization, hemodynamic alterations have been used to treat these lesions. In every aspect of treatment, technological advances, including catheters, embolic materials, angiography suites, and pharmacological agents, have improved outcomes while lowering the risk to patients. In this article, the authors review the technical evolution of endovascular AVM therapy. Developments in embolic materials, beginning with foreign bodies and autografts and continuing through to highly engineered contemporary substances, are discussed. Finally, changes in treatment paradigms that have occurred over the years are traced. Within neurosurgery, this specialty has shown some of the fastest growth and development in recent decades. As minimally invasive approaches are embraced in all areas of medicine, it is clear that this treatment modality will continue to be refined.

Nongalenic arteriovenous fistulas: history of treatment and technology.

Nongalenic cerebral arteriovenous fistulas (AVFs) are uncommon, high-flow vascular lesions first treated by Walter Dandy and his colleagues by using open surgery with ligation of the feeding artery. Due to advances in endovascular technology over the past four decades that make possible the control of high flow in AVFs, treatment has evolved from the sole option of surgery to include the alternative or adjunct option of endovascular embolization. The authors of this review discuss the history of nongalenic AVF treatment, including techniques of both surgery and interventional neuroradiology and the technological developments underlying them.

Harvey W. Cushing and cerebrovascular surgery: Part II, Vascular malformations.

The surgical treatment of cerebrovascular malformations intrigued early neurosurgeons. Cushing defined vascular malformations as tumors arising from cerebral blood vessels. He successfully resected the first arteriovenous malformation 3 years after it had been irradiated. In the absence of angiography, the pathoanatomy of these lesions remained elusive and early techniques such as cortical vein ligation proved catastrophic. Cushing demonstrated the favorable results of radiation treatments on vascular malformations and advocated decompressive craniectomy followed by radiotherapy. He ligated cortical feeding vessels and external carotid arteries with an improved understanding of the angioarchitecture of vascular malformations. He stressed the importance of preoperative diagnosis because the radical resection of nonirradiated vascular malformations challenged the limitations of the available neurosurgical armamentarium.

A tribute to Helge Nornes.

This supplement of the Acta Neurochirurgica is dedicated to professor Helge Nornes on the occasion of his retirement. Helge Nornes started his neurosurgical training in Oslo in 1965. In 1980 he was offered the neurosurgical chair of Bern, Switzerland, where he stayed until 1983 when his old university called him back to the chair at the National Hospital in Oslo, a position he filled until he retired last year. The present paper briefly reviews examples of his contributions to neurosurgery and to the understanding of intracranial pathophysiology, including the transcranial doppler, the miniature transducer for intracranial pressure monitoring, his observations on intracranial pressure and internal carotid blood flow during subarachnoid haemorrhage, intracranial arterial blood flow in patients undergoing aneurysm surgery, his studies of the pathophysiology of arteriovenous malformations, the introduction of intraoperative Doppler recordings during surgery for aneurysms and arteriovenous malformations, and his methods for evaluating collateral circulation prior to internal carotid artery occlusion.

The death of Sir Thomas Stamford Raffles (1781-1826).

The authors reviewed a rare autopsy report of Sir Thomas Stamford Raffles and offer a fresh interpretation of the cause of his death, with illustrations on the implied findings.