Lindsay Symon: A giant of stroke

Professor Lindsay Symon, the leader of the team that discovered the ischemic penumbra, passed away aged 90 on 2 December 2019. He was a brilliant neurosurgeon and neuroscientist and played a pivotal role in our understanding of the evolving pathophysiology of acute ischemic stroke, which directly led to the advent of modern reperfusion therapies. He was born in Aberdeen, Scotland in 1929 and graduated from Aberdeen University in 1951 in medicine with Honours and the Lyon Prize for the most distinguished medical graduate. He had won Gold medals in Anatomy, Pathology, Materia Medica, Medicine and Surgery. He was House Officer to the Professorial Units in Medicine and Surgery in the Royal Infirmary, Aberdeen, and then Registrar and Senior Registrar at Middlesex and Maida Vale Hospitals, London. In 1965, he was appointed Consultant Neurosurgeon at the Institute of Neurology and the National Hospital, Queen Square, London, and in 1978, Professor of Neurological Surgery in London University. He was Senior Surgeon until his retirement in 1995. He was an internationally renowned academic neurosurgeon, a natural and gifted leader and teacher, with a sonorous Scottish accent and a lifelong love of golf and travel. He was President of theWorld Federation of Neurosurgical Societies from 1989 to 1993, was named Commander of the British Empire in 1994, and was awarded numerous national and international prizes. These included the John Hunter Medal of the Royal College of Surgeons in England for his cerebrovascular research. As a young neurosurgeon, he developed a strong interest in cerebrovascular diseases, notably subarachnoid hemorrhage (SAH) and post-SAH vasospasm. Thanks to an MRC Clinical Research fellowship, he was able to carry out laboratory research on the pathophysiology of the cerebral circulation at the National Institute for Medical Research, Mill Hill, London. He then continued this theme with a Rockefeller travelling fellowship at Wayne State University, Detroit, in John Sterling Meyer’s laboratory. His early experimental work, first published 60 years ago, included the study of pial anastomoses and their involvement in maintaining perfusion pressure following proximal occlusion of the middle cerebral artery (MCA) first in dogs (using P labelled erythrocytes) and subsequently in macaques, and the development of cervical anastomoses following chronic carotid occlusion in baboons. His interest then focused on understanding the mechanisms underlying the fluctuations in neurological deficit following aneurysmal surgery, which at the time was widely considered to be due to cerebral edema. He made parallels with the fully reversible focal neurological deficits characterizing transient ischemic attacks, which were then empirically given vague explanations such as ‘‘hypertensive crisis’’ or ‘‘arterial spasm.’’ Regarding ischemic stroke, the then prevalent dogma was that, akin to cardiac arrest, neurons would die within minutes of the onset of stroke, while spontaneous recovery reflected resolution of edema. To explain these clinical observations, he developed a revolutionary concept that went completely against all thinking at the time, namely that some critical level of brain perfusion must exist to account for such potentially reversible neurological deficits. To address this hypothesis, he turned to the MCA occlusion model, which had only been established for large mammals such as the dog, the cat and the nonhuman primate. On his return from the US, and with the support of the MRC, he created the Laboratory of Experimental Neurosurgery, at the Institute of Neurology, Queen Square, London, and recruited a team of gifted research technicians and young neurophysiology and neurosurgical fellows (Figure 1). There he developed a model of reversible proximal MCA occlusion in the baboon by means of a microsurgical clip. His decision to study non-human primates was based on his previous work showing that the anatomy of the cerebral circulation of the dog and cat had major differences with that of primates including humans. Rodent models of focal cerebral ischemia had not yet been developed. He took advantage of recently developed techniques to assess neuronal activity and brain perfusion simultaneously at several cortical locations using probes positioned at the surface of or inserted within brain tissue in baboons subjected to temporary proximal MCA occlusion. The initial experiments, performed by the group in the early 70s, showed that, because of the presence of pial anastomoses, cortical perfusion was not completely abolished in the MCA territory, but showed a gradient of reductions from mild hypoperfusion close to the