Charcot's international visitors and pupils from Europe, the United States, and Russia.

The foundation by Jean-Martin Charcot (1825-1893) of the Salpêtrière School in Paris had an influential role in the development of neurology during the late-nineteenth century. The international aura of Charcot attracted neurologists from all parts of the world. We here present the most representative European, American, and Russian young physicians who learned from Charcot during their tutoring or visit in Paris or Charcot's travels outside France. These include neurologists from Great Britain and Ireland, the United States, Germany and Austria, Switzerland, Russia, Italy, Spain, Belgium and the Netherlands, Scandinavia and Finland, Poland, Bohemia, Hungary, and Romania. Particularly emblematic among the renowned foreign scientists who met and/or learned from Charcot were Charles-Edouard Brown-Séquard, who had interactions with Paris University and contributed to the early development of British and American neurological schools; John Hughlings Jackson, who was admired by Charcot and influenced French neurology similarly as Charcot did on British neurology; Silas Weir Mitchell, the pioneer in American neurology; Sigmund Freud, who was trained by Charcot to study patients with hysteria and then, back in Vienna, founded a new discipline called psychoanalysis; Aleksej Yakovlevich Kozhevnikov and almost all the founders of the Russian institutes of neurology who were instructed in Paris; and Georges Marinesco, who established the Romanian school of neurology and did major contributions thanks to his valuable relation with Charcot and French neurology.

The stone of madness: Charcot's interest in a copy after Pieter Bruegel Sr. as referred to by Henry Meige.

Jean-Martin Charcot (1825-1893) is known to have possessed interesting works of art, e.g. Jan Steen's Marriage at Cana. In 1899, his pupil and colleague Henry Meige (1866-1940) wrote that Charcot had been interested in a painting (after a drawing) by Bruegel, named Les Arracheurs de Pierres de Teste. At the time the painting belonged to Charcot's contemporary Ernest Mesnet (1825-1898). When Charcot visited Mesnet, he offered him a considerable amount of money. The owner did not want to sell it, but promised to leave it to Charcot in his will. As Charcot died earlier than Mesnet, the painting went to the latter's heirs. In 1899, it was possessed by dermatologist dr. Paul de Molènes-Mahon (b. 1857). Meige published an article, in which he criticized the quality of the copy. Surgeon Henri Gaudier (1866-1942) wrote about the original painting in the Museum of St. Omer and confirmed Meige's opinion about the copy. I will illustrate the St. Omer painting and describe Meige's and Gaudier's comments by comparing it with the black & white copy in Meige's 1899 article. My study looks at Charcot as a collector of paintings, which is a minimally studied topic. He may have been interested in the Paris Bruegel copy for clinical and medical-historical reasons, rather than on aesthetic grounds.

History of migraine.

Migraine symptoms were described in ancient Babylonia, and supernatural forces were felt to play a role in etiology and treatment. This changed in the Greco-Roman period, when the (dis)balance of humors was considered in (patho)physiology and treatment based on this. Aretaeus distinguished between cephalalgia, cephalea, and heterocrania. The latter term was changed to hemicrania by Galen. Physicians in the 17th century attributed headache to the meninges, extracranial periost, and cranial blood vessels. As for the pathophysiology, Willis suggested intracranial vasoconstriction with subsequent dilatation. Tissot and Fothergill gave comprehensive descriptions of migraine, including visual symptoms. Symptomatic and idiopathic hemicrania were distinguished in the early 19th century. Vasomotor pathophysiology was scientifically studied in the 1860s, leading to sympathicotonic and angioparalytic theories. Latham combined them, stating the latter follows the first. Ergot was introduced in 1868; ergotamine was isolated in 1918. This led to the vasodilatation theory of migraine (Wolff), the discovery of 5-HT, and later the specific agonists. Aura and cortical spreading depression were studied in the early 1940s and related to spreading oligemia in the 1980s. Subsequently, hyperemia followed by oligemia after CSD was found. After the discovery of CGRP, a new a class of drugs became the subject of clinical studies.

Berlin Bowel Bothers: Might Adolf Hitler's Gut Problems Have Been Parkinson-Related?

It has been argued that Adolf Hitler (1889-1945) had Parkinson's disease. He also experienced several gastrointestinal symptoms, for which various explanations have been sought, both contemporaneously and by later authors. In this Historical Note, a possible relationship between Hitler's Parkinson's disease and his gastrointestinal symptoms is explored. Specifically, we posit the hypothesis that Hitler may have suffered from small-intestinal bacterial overgrowth (SIBO), thus providing an early example of SIBO occurring as a prodromal Parkinson's disease symptom.

Neuropathological images in the great pathology atlases.

In the period between Morgagni's De Sedibus (1761) and Cruveilhier's Anatomie pathologique (1829-1842), six pathology atlases were published, in which neuropathological subjects were discussed and depicted. It was a period of transition in medical, technical, and publishing areas. The first three (by Matthew Baillie, Robert Hooper, and Richard Bright) were mainly atlases derived from pathological museum specimens. They were selective rather than comprehensive. Of the other three (by Jean Cruveilhier, James Hope, and Robert Carswell), most of the observations were made during autopsies. These illustrations required special arrangements so they could be executed during the autopsies. These were available in Paris rather than in London, which is the reason why Hope and Carswell made many of the drawings in France. The plates in these three were color lithographs. Baillie's book contains only figure descriptions. Bright's and Cruveilhier's atlases provide case descriptions. Hooper and Hope provide theoretical texts and figure legends. Carswell's book has 12 theoretical sections, each followed by plates. The relative cost of the atlases varied with the number of plates. Although the authors made use of artists and engravers, several were talented artists themselves. Many common neurological diseases were depicted.

Ada Potter and her microscopical neuroanatomy atlases.

In his Recollections (1947), Dutch neuropsychiatrist Cornelis Winkler mentioned his colleague Ada Potter, who made many of the neuroanatomic drawings in his publications. She also made two microscopical brain atlases (of a rabbit and a cat) and participated in endeavors to publish a human brain atlas. Born on East Java (Dutch East Indies), Potter received her M.D. from the University of Amsterdam. She worked with Winkler until his retirement (1926) and then moved to the United States. Subsequently, she went back to East Java, practicing in an insane asylum. In the meantime, she was active in the women's mancipation movement. After a short stay in Geneva, she returned to the Netherlands in 1939. The rabbit and cat atlases (1911 and 1914, respectively) were major projects that served animal experimenters up to the 1980s. They consist of 40 and 35 black-and-white plates, respectively, depicting microscopic fiber and cell structure drawings with extensive legends. In a period in which medical photography had fully developed, they preferred drawings, particularly because neurons in thick microscopical slices can only be seen by continuous focusing. The choice was shared by well-known neuroanatomists, such as Ramon y Cajal, who noted that drawing facilitates analysis and teaches scientists how to see.

On the Threshold of Scientific Medicine: Gerard van Swieten and His Perception of the Pathophysiology in Traumatic Brain Injury.

Gerard van Swieten (1700-1772), famous pupil of Professor Herman Boerhaave (1668-1738) of Leiden University and personal physician of Austrian Habsburg Empress Maria Theresa (1717-1780). Herman Boerhaave was a renowned Dutch physician inside and outside Europe in the 18th century. He was not only appointed professor in medicine, chemistry, and botany but also a chancellor of the Leiden University in 1714 and published his well-known Aphorismi de cognoscendis et curandis morbis in 1709. Gerard van Swieten commented upon Boerhaave's aphorisms and demonstrated actual knowledge, less well-known among the medical community, about the pathophysiology of traumatic brain injury which half a century later (19th century) became known as the Monro-Kellie doctrine. Using the original commentaries upon Boerhaave's aphorisms by van Swieten himself, we explored his way of formulating the pathophysiological concept of traumatic brain injury, which still is valid today.

Worth Their Salt: One Hundred Years of Hyperosmolar Therapy.

In this article, we commemorate the centenary of the discovery and clinical implementation of hyperosmolar therapy for the treatment of increased intracranial pressure (ICP). Following the pioneering work of anatomists Weed and McKibben in 1919, the use of hypertonic solutions was soon adopted into clinical practice, even though the preferred hypertonic agent, route of administration, and ideas regarding the physiological mechanism by which it reduced ICP diverged. These divergent conceptions and practices have continued to surround the use of hyperosmolar therapy into present times.

Myelography and the 20th Century Localization of Spinal Cord Lesions.

In this article, we commemorate the centenary of myelography, a neuroradiological procedure that, despite certain disadvantages, significantly contributed to the diagnosis and localization of spinal cord lesions during the 20th century. From the start, the use of myelography was characterized by different views regarding the potential dangers associated with the prolonged exposure of a "foreign body" to the central nervous system. Such differences in attitude resulted in divergent myelography practices; its precise indications, technical performance, and adopted contrast material remaining subject to variability until the procedure were eventually replaced by MRI at the close of the 20th century.

The Origin of the Idea That Herpes Labialis Is of Prognostic Importance in Bacterial Meningitis.

OBJECTIVE: The aim of the work was to study the origin of the idea that herpes labialis (HL) in patients with pneumonia and meningitis was believed to be of prognostic importance. BACKGROUND: HL is caused by a primary infection or reactivation of herpes simplex type I. In the past, it has been related to pneumonia and meningitis; moreover, HL was believed to be of prognostic importance. METHODS: A selection of 19th- and 20th-century textbooks and referred articles was consulted. The relation between meningitis and herpes, type of meningitis, and attributed diagnostic and prognostic importance were studied. In addition, the HL-pneumonia association was studied. RESULTS: The Strasbourg physician Charles-Polydore Forget was the first to describe the HL-meningitis association in 1843. Tourdes (1843), Drasche (1859), and Salomon (1864) attributed a favorable prognostic importance to the HL-meningitis relation. In a comprehensive monograph (1866), August Hirsch, although confirming the association, denied the prognostic importance through critical analysis of the data. Few authors attributed a diagnostic importance to the occurrence of HL, suggesting meningococcal meningitis. CONCLUSIONS: The HL-meningitis relation, but not the prognostic importance, has been mentioned in most neurological textbooks since then. In contrast to meningitis, in which a prognostic attribution of HL was only a short-lived 19th-century idea, the favorable prognostic importance of HL in pneumonia continued to be described until the 1950s. A possible protective effect of herpesviruses has been found in recent years. One could speculate that the disappearance of the prognostic HL-pneumonia relation could be related to the introduction of antibiotics in the late 1940s.

Neurosyphilis Mimicking Autoimmune Encephalitis: A Case Report and Review of the Literature.

Neurosyphilis may imitate a wide range of neurological and psychiatric diseases, including autoimmune encephalitis. To avoid further cognitive decline and morbidity, early recognition and adequate treatment are of particular importance in both neurosyphilis and autoimmune encephalitis. In case of a strong clinical suspicion of a diagnosis of autoimmune encephalitis, guidelines recommend initiating immunotherapy even in the absence of immunological confirmation. Here, a case of neurosyphilis is reported in which the potential overlap in clinical presentation of autoimmune encephalitis and parenchymatous neurosyphilis is discussed. The here reported data suggest that, in cases presenting with new onset focal epilepsy, slowing of electroencephalographic activity over the temporal regions and magnetic resonance imaging suggestive of swelling of the amygdala, neurosyphilis should be excluded prior to initiation of immunotherapy for suspected autoimmune encephalitis.

Clinical Presentation of Laboratory Confirmed Neurosyphilis in a Recent Cases Series.

OBJECTIVE: The worldwide increase in the incidence of syphilis necessitates alertness to the occurrence of neurosyphilis. Early recognition of neurosyphilis allows for timely treatment, leading to a better treatment outcome. This retrospective study aims to describe the clinical presentation of neurosyphilis in a recent series of neurosyphilis patients. METHOD: All patients were included with a new, laboratory confirmed, diagnosis of neurosyphilis in the period 2004-2018. The clinical data were analysed. RESULTS: 34 neurosyphilis patients (1 woman and 33 men) were identified. Age varied from 31-84 years (median age: 44 years). A history of syphilis infection was known for 11 (32%) patients; 12 (35%) patients were HIV seropositive. The distribution of the clinical syndromes was as follows: 16 patients with early neurosyphilis (acute meningitis, meningovasculitis and/or uveitis), 9 patients with late neurosyphilis (General Paralysis of the Insane and/or Tabes Dorsalis), 2 patients with symptoms of both early and late neurosyphilis, 6 patients with asymptomatic neurosyphilis and in 1 patient insufficient data were available to determine a clinical syndrome. Early neurosyphilis was seen in all age categories, late neurosyphilis only occurred in patients > 40 years. CONCLUSIONS: Neurosyphilis occurs in adults in all age groups, in men more frequent than in women, often in HIV-infected patients, and can present with a wide range of clinical syndromes. Usually no previous infection with syphilis is known.

Oxygen treatment for cluster headache attacks at different flow rates: a double-blind, randomized, crossover study.

BACKGROUND: Cluster headache attacks can, in many patients, be successfully treated with oxygen via a non-rebreather mask. In previous studies oxygen at flow rates of both 7 L/min and 12 L/min was shown to be effective. The aim of this study was to compare the effect of 100% oxygen at different flow rates for the treatment of cluster headache attacks. METHODS: In a double-blind, randomized, crossover study, oxygen naïve cluster headache patients, treated attacks with oxygen at 7 and 12 L/min. The primary outcome measure was the percentage of attacks after which patients (treating at least 2 attacks/day) were painfree after 15 min, in the first two days of the study. Secondary outcome measures were percentage of successfully treated attacks, percentage of attacks after which patients were painfree, drop in VAS score and patient preference in all treatment periods (14 days). RESULTS: Ninety-eight patients were enrolled, 70 provided valid data, 56 used both flow rates. These 56 patients recorded 604 attacks, eligible for the primary analysis. An exploratory analysis was conducted using all eligible attacks of 70 patients who provided valid data. We could only include 5 patients, treating 27 attacks on the first two days of the study, for our primary outcome, which did not show a significant difference (p = 0.180). Patients tended to prefer 12 L/min (p = 0.005). Contradicting this result, more patients were painfree using 7 L/min (p = 0.039). There were no differences in side effects or in our other secondary outcome measures. The exploratory analysis showed an odds ratio of being painfree using 12 L/min of 0.73 (95% CI 0.52-1.02) compared to 7 L/min (p = 0.061) as scored on a 5-point scale. The average drop in score on this 5-point scale, however, was equal between groups. Also slightly more patients noticed, no or not much, relief on 7 L/min, and found 12 L/min to be effective in all their attacks. CONCLUSION: There is lack of evidence to support differences in the effect of oxygen at a flow rate of 12 L/min compared to 7 L/min. More patients were painfree using 7 L/min, but our other outcome measures did not confirm a difference in effect between flow rates. As most patients prefer 12 L/min and treatments were equally safe, this could be used in all patients. It might be more cost-effective, however, to start with 7 L/min and, if ineffective, to switch to 12 L/min. TRIAL REGISTRATION: European Union Clinical Trials Register ( 2012-003648-59 ), registered 1 October 2012. Dutch Trial Register ( NTR3801 ), registered 14 January 2013.

The founding of neurology as a specialty: The American situation in context.

With few exceptions, neurology in Europe as well as in the United States emerged from internal medicine and psychiatry, and neurology and psychiatry in particular have long remained connected in clinical practice and teaching. When the American Board of Psychiatry and Neurology (ABPN, 1934) and the American Academy of Neurology (AAN, 1948) were founded, the emancipation of neurology as an independent specialty was still evolving. During the First International Neurological Congress (Berne, Switzerland, in September 1931), a special conference was organized on the "Relation of Neurology to General Medicine and Psychiatry in Universities and Hospitals of the Various Countries," at which representatives from several countries described the situation in their countries. Their statements were made around the time of the founding of the ABPN and not long before that of the AAN. They show that neurology in most countries was still struggling to become independent and only in a few cities flowered as an independent specialty. In the second part of this article, specialist regulation (training, examination, and certification) in European countries (Germany, France, England, and The Netherlands) will be compared to that of the ABPN. It appears that Germany was among the early countries where this occurred, following the Bremen Ärztetag (physicians day) in 1924. Comparable to the American situation, it was professionally controlled, in contrast to the French state certification, which occurred later. The British specialist regulation was much later and more complicated.

The Four Horsemen and the American Board of Psychiatry and Neurology (ABPN).

After the gradual introduction of specialties in medicine in the United States during the late-nineteenth and early-twentieth centuries, the American Board of Psychiatry and Neurology (ABPN) was founded in 1934 to provide specialty regulation (training oversight, examination, and certification). The name reflects the combined practice of psychiatry and neurology that was still present at the time. Directors were nominated by the founding organizations: American Psychiatry Association (APA), American Neurological Association (ANA), and the Section of Nervous and Mental Diseases of the American Medical Association (AMA). Many of the early physicians who were certified by the ABPN did so for psychiatry as well as neurology. Neurologist Walter Freeman and psychiatrist Adolph Meyer played important roles in the ABPN during the early days. Following the founding of the AAN in 1948, neurological practitioners believed the AAN would better represent them in the ABPN. At first the ANA appointed AAN members to the ANA Council; but after 1972, the AAN could directly nominate directors for the ABPN. Despite this situation, the AAN had an important influence in the ABPN from its start, as is shown by the fact that all of the key organizational leaders responsible for founding the AAN-the "Four Horsemen" (Abraham B. Baker, Russell N. DeJong, Francis M. Forster, and Adolph L. Sahs-served as directors of the ABPN in the period 1951-1967. The Horsemen were able to change both examination practices that became more searching and expansive, and the basic disciplines that needed to be studied in detail.