Although changes in pupils in moribund patients have been known since antiquity, laboratory studies that focused on measurements of the consequences of acute mass effect in the brain provided the first pieces of information that led to a better understanding of its pathophysiological meaning. Its significance was not known before the 19th century. It is well known that Cushing did similar experiments in Berne (1900–1901), and later suggested he would not have done so if he had studied the literature.Ī light- fixed and dilated pupil is considered an iconic sign in acute neurology and neurosurgery, and has been considered a grave sign.
Following the period of extensive experimental research in ICP, the results of which were translated to clinical observations, the prognostic significance was gradually acknowledged by authors of neurological textbooks. The key observation of a fixed dilated pupil as a sign of acute mass effect came gradually and after some localization stumbles. Concentrating on experimental traumatic effects, Duret (1878) investigated compression and commotion, in which he distinguished two phases, notably pupil constriction by bulbar lesions, due to CSF shock, followed by dilation from congestion and inflammation, due to blood around the oculomotor nerve. Naunyn and Schreiber (1881) understood the relationship between increased ICP with pupil dilation and decreased pulse frequency and blood pressure, warning not to decrease the latter. Probably confusing irritation (epileptic head turning to the other side with pupil dilation) and lesion effects, he suggested a cortical area responsible for oculomotor phenomena, indicating what is now known as the frontal eye field. He distinguished the extent of pressure increase and its duration. In 1880, von Bergmann emphasized the significance of the ipsilateral dilation in experiments as well as in clinical cases. Pagenstecher in 1871 extended knowledge by meticulously studying consecutive pupil phenomena with increasing pressure. Asymmetrical dilation could not always be attributed to increased ICP, but to an oculomotor nerve lesion. Along with bradycardia and motor and respiratory effects, he noticed wide pupils were usually present in a comatose state. Von Leyden's 1866 animal experiments, in which he increased CSF volume by injecting protein solutions intracranially, was the first observation in which the association between fixed dilated pupils and increased ICP was established.
Realizing the unreliability of the pupil sign, Hutchinson in 1867–1868 tried to reason in which cases trepanation would be advisable. Bright demonstrated to have some knowledge of the pupil sign (clinical observations). He described dilated pupils in clinical cases without referring to the effect of light. Cooper experimented with intracranial pressure (ICP) in a dog in the 1830s, but did not mention the pupils. Medical and neurological textbooks from the 19th and 20th centuries were reviewed to investigate when and how this information percolated through neurological and neurosurgical practices. Starting from Kocher's standard review in 1901, the authors studied German, English, and French texts for historical information. The aim of this study was to investigate the development of ideas about the nature and mechanism of the fixed dilated pupil, paying particular attention to experimental conditions and clinical observations in the 19th century.
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