Brain disease caused by purulent clots obstructing venous sinuses in children was the first and, for a long time, the only recorded variant of cerebral venous thrombosis. These early cases were secondary to septic inflammation, either elsewhere in the body (de Haen, 1759) or in the mastoid region (Abercrombie, 1818). In 1829, Tonnellé recorded more clinical and morphological details in a large series of children with cerebral phlebitis. Soon afterwards, Bright and Cruveilhier confirmed and illustrated the attendant changes in brain tissue.

In the middle of the nineteenth century, small holes in deep regions in the brain were recognized as widened perivascular spaces (Durand-Fardel: ‘état criblé’). Later researchers (Laborde, Proust, Campbell) reported in these areas some larger cavities with ragged borders, presumably damaged brain tissue (‘lacunes’); these authors did not correlate such lesions with symptoms, and their pathogenesis remained unclear.

The contents of this book reflect, I hope, how excellent my teachers have been – in neurology, language, and history. Hans van Crevel (1931–2002) and Arthur Staal (1926–2016) in Rotterdam have been my role models in all aspects of academic medicine. More recently, the passion and erudition of Piet Gerbrandy, Charles Hupperts, Rodie Risselada, and David Rijser of the Department of Classical Languages at the University of Amsterdam made me forget that studying Latin had been undertaken as the means to an end. Back at the University of Utrecht, studying ‘History and Philosophy of Science’, I found the methods of historians of science more difficult to penetrate than those of physicians or linguists, despite the efforts of especially Frank Huisman and Dirk van Miert. I hope my ‘history of ideas’ has been contextualized at least to some extent, though surely many deeper layers have been left unexplored.

The French Revolution accelerated the increase of medical knowledge. Rochoux, a typical exponent, dissected several patients who had died of apoplexy. In his view, sudden hemiplegia always signified a haemorrhage in the brain. He regarded other brain lesions, particularly serous effusion and softening, found always after an interval of at least one month, as secondary complications. However, Riobé, Cruveilhier, and Moulin soon elucidated the usual course of tissue changes following intracerebral haemorrhage. Elsewhere, Abercrombie distinguished forms of apoplexy according to the initial symptoms: loss of consciousness, headache, or paralysis. Serres categorized brain haemorrhage without paralysis as ‘meningeal apoplexy’.

In one of the four patients with apoplexy, Wepfer described in 1658 the excess of fluid in the brain was not blood, but ‘serum’ – a gelatinous form of it covered the entire surface. Wepfer therefore distinguished ‘serous apoplexy’ from the sanguineous form, even though the apoplectic state had occurred as part of a protracted illness. Later he reported similar cases. In retrospect, thanks to Wepfer’s meticulous recording, a retrospective diagnosis of chronic infectious disease seems inescapable. In the eighteenth century, Boerhaave and van Swieten implicated the accumulation of brain lymph as a cause of apoplexy, but without providing anatomical proof. In Morgagni’s large series of dissections, patients classified as having ‘serous apoplexy’ showed a variety of lesions; in a patient with ‘paralysis’, he found unilateral ‘erosion’ of the striate body, like Willis before him. In the decades around 1800, once it had become fashionable to diagnose apoplexy in a variety of attacks, the ‘serous’ form was considered less often.

An X-ray is directed at the skull. Its energy is largely absorbed when it meets the dense layers of calcium. Whatever is left traverses brain tissue almost without resistance and is then once again decimated by the other side of the skull. If a morsel of energy is left at all, it makes virtually no imprint on the photographic plate: a blank spot. All X-rays together produce a negative outline of the skull. Though the brain has been traversed, it does not contribute to the image.

In the eighteenth century, most diseases were still ill-defined and explained by local or remote causes. The diagnosis of ‘apoplexy’ was applied in a broad sense, with unresponsiveness as the cardinal symptom and overfilling of the skull or its vessels as the key event. Its purported causes included not only primary changes in or around the brain (Boerhaave), but also the general constitution and external circumstances. Thus, two doctrines of attributing causality more or less coexisted in the ‘long eighteenth century’, up to the 1820s. One was the morphological approach, practised in Vienna (de Haen) and Bologna (Valsalva), and especially in Padua (Morgagni distinguished three kinds of apoplexy: haemorrhagic, serous, and ‘other’). The other doctrine, related to Galen’s ‘fluidism’ and only slowly losing ground, implicated mainly external factors as the cause of fullness in the head (Portal).

Around the mid-nineteenth century, it became commonly known that the deficits of brain softening had sometimes been preceded by temporary attacks of the same kind (hemiplegia, disorders of language). In the middle of the twentieth century, Fisher recognized that episodes of monocular blindness, identified in 1898 as embolic (Knapp), were also potential harbingers of cerebral ischaemia. Studies addressing the risk of stroke after such warnings, conducted in the 1960s and early 1970s, were sparse and difficult to interpret.

Hippocratic and Galenic texts, fully rediscovered in the first half of the sixteenth century, defined apoplexy as a sudden collapse, with loss of movement and sensation, except for preserved heart action and respiration. Though this definition leaves room for divergent interpretations, early physicians who made the diagnosis rarely specified the symptoms.

Descriptions of superficial haemorrhages and of saccular aneurysms at the base of the brain appeared separately in the medical literature, before the first report of a ruptured basal aneurysm in 1813 (Blackall). This first patient was young, a recurrent characteristic in many later observations. Since the diagnosis was made only at autopsy, a fatal outcome seemed to be the rule, until preceding episodes of sudden, unusually severe headache were recognized (Stumpff, Wichern). A distinctive feature of ruptured aneurysms of the internal carotid artery was attendant oculomotor palsy (Stumpff); this allowed the first diagnosis during a patient’s life, in 1920 (Symonds). Less specific were neck stiffness, retinal haemorrhages (Litten), caused by rupture of swollen veins (Terson, Manschot), and, after the introduction of lumbar puncture (Quincke, 1891), the demonstration of bloodstained cerebrospinal fluid.

In an early part of his career, Virchow established that intravascular clotting is unrelated to inflammation, and also that clots can be dislodged and carried along, until they become stuck (embolism). The young Charcot, on reading this, proposed embolism as the cause in some hitherto unexplained post-mortem findings; wider acceptance took time.

Rochoux had equated ‘apoplexy’ with intracerebral haemorrhage, but he also reported a few rare and unexplained cases of softening, ‘simulating apoplexy’. Others tentatively proposed ‘essential softening’ as a separate disease. Rostan in 1820 made this a postulate, but since his starting point was softening of brain tissue, he included patients in whom the state of ‘apoplexy’ represented not the onset, but an aggravation of pre-existing illness. He interpreted non-focal premonitory symptoms as the initial stage of the disease; this was followed by a phase of focal deficits. Rostan explicitly opposed the idea that softening was an inflammatory condition, a hypothesis to which Lallemand and others adhered, following Broussais’ popular ‘irritation theory’. Fuchs, insisting on paralysis as the essential feature, excluded inflammation as the cause of any form of ‘encephalomalacia’.

Harvey’s description of the circulation of blood slowly replaced Galen’s theory. The ancient model had taught that the liver synthesized new blood, to be subsequently consumed by body organs; the liver also transported the blood to abdominal organs, and the heart supplied mainly the chest and all muscles.

In the late 1880s, Mehnert, performing a systematic study of ‘angiosclerosis’, found the internal carotid artery commonly affected; a few years later, Chiari identified it as a source of thrombo-embolism to the brain. Yet, throughout the first half of the twentieth century, the role of the extracranial arteries remained underestimated, for two reasons: the presence of communicating arteries and the ‘concealed’ location of the neck arteries, between the brain arteries and known sources of embolism. Primary atherothrombosis of intracerebral arteries was commonly assumed, even though arteries supplying a softened area could be found patent and intact (Foix and Ley).