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.

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.

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.

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.

EMR + with the AWC improves endoscopic resection speed compared to ESD: a porcine ex-vivo pilot study.

INTRODUCTION: To improve resection speed and to reach higher en bloc resection rates in lesions ≥ 2 cm, a novel grasp and snare EMR technique termed "EMR+", accomplished by an additional working channel (AWC), was developed. Its use compared to endoscopic submucosal dissection (ESD) is evaluated for the first time. MATERIAL AND METHODS: We prospectively conducted a randomized pre-clinical ex-vivo pilot study in explanted porcine stomachs for the comparison of EMR + with classical ESD of mucosal-based lesions. Prior to intervention, we set flat lesions with a standardized size of 3 × 3 cm. RESULTS: The median time of procedure was significantly shorter in the EMR + group (median 10.5 min, range 4.4-24 min) than in the ESD group (median 32 min, range 14-61.6 min, p < .0001). The rate of en bloc resection was significantly lower in the EMR + group (38 % vs. 95 %) (p < .0001). Nevertheless, an improvement in the learning curve for EMR + was achieved after the first 12 procedures, with a subsequent en bloc resection rate of 100 %. CONCLUSIONS: EMR + could improve the efficiency of mucosal resection procedures. Initial experience demonstrates a higher and satisfactory en bloc resection rate after going through the learning curve of EMR+.

The Two Faces of Wheat.

Wheat-based foods have been staple foods since about 10,000 years and constitute a major source of energy, dietary fiber, and micronutrients for the world population. The role of wheat in our diet, however, has recently been scrutinized by pseudoscientific books and media reports promoting the overall impression that wheat consumption makes people sick, stupid, fat, and addicted. Consequently, numerous consumers in Western countries have started to question their dietary habits related to wheat consumption and voluntarily decided to adopt a wheat-free diet without a medical diagnosis of any wheat-related disorder (WRD), such as celiac disease, wheat allergy, or non-celiac gluten sensitivity. The aim of this review is to achieve an objective judgment of the positive aspects of wheat consumption as well as adverse effects for individuals suffering from WRDs. The first part presents wheat constituents and their positive nutritional value, in particular, the consumption of products from whole-grain flours. The second part is focused on WRDs that affect predisposed individuals and can be treated with a gluten-free or -reduced diet. Based on all available scientific knowledge, wheat consumption is safe and healthy for the vast majority of people. There is no scientific evidence to support that the general population would benefit from a wheat-free diet.

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.

Comparative quantitative LC-MS/MS analysis of 13 amylase/trypsin inhibitors in ancient and modern Triticum species.

Amylase/trypsin inhibitors (ATIs) are major wheat allergens and they are also implicated in causing non-celiac gluten sensitivity and worsening other inflammatory conditions. With only few studies on ATI contents in different Triticum species available so far, we developed a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) method based on stable isotope dilution assays to quantitate the 13 most important ATIs in a well-defined sample set of eight cultivars of common wheat and durum wheat (modern species), as well as spelt, emmer and einkorn (ancient species) grown at three locations in Germany, respectively. Only few ATIs with low contents were detected in einkorn. In contrast, spelt had the highest total ATI contents. Emmer and common wheat had similar total ATI contents, with durum wheat having lower contents than common wheat. Due to the lack of correlation, it was not possible to estimate ATI contents based on crude protein contents. The wheat species had a higher influence on ATI contents than the growing location and the heritability of this trait was high. Despite comparatively low intra-species variability, some cultivars were identified that may be promising candidates for breeding for naturally low ATI contents.

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.

Further Steps Toward the Development of Gluten Reference Materials - Wheat Flours or Protein Isolates?

Celiac disease is a gluten-induced hypersensitivity reaction that requires a lifelong gluten-free diet. Gluten-free foods must not contain more than 20 mg/kg gluten as laid down by Codex Alimentarius. Measuring the presence of gluten with routine immunoanalytical methods in food is a serious challenge as many factors affect accurate determination. Comparability of the results obtained with different methods and method validation are hindered by the lack of a widely accepted reference material (RM). The core questions of RM development from wheat are the number of cultivars to be included and the format of gluten (i.e., flour, gluten, or gliadin isolates) to be applied. Therefore, the aim of our work was to produce an appropriate gluten RM from wheat. For this, five previously selected wheat cultivars and their blend were used to produce flours, gluten and gliadin isolates under laboratory conditions. Protein content, protein composition and responses to different ELISA methods were compared and widely evaluated in our study. The protein contents of the flours were 12.1-18.7%, those of the gluten isolates 93.8-97.4% and those of the gliadin isolates 72.7-101.9%. The gluten and gliadin isolates had similar protein profiles as the source flours. By comparing the different wheat cultivars and their protein isolates, we found that the isolation had a smaller effect on protein composition than genetic variability. The choice of a blend would be more suitable for the production of a RM in case of flours and also isolates. The immunoanalytical results showed that the isolation had an effect on the analytical results, but its extent depended on the ELISA method. The use of flour would be more applicable in this regard, but handling of the material and long-term stability should also be considered in the final decision of gluten RM production.

Recent Progress and Recommendations on Celiac Disease From the Working Group on Prolamin Analysis and Toxicity.

Celiac disease (CD) affects a growing number of individuals worldwide. To elucidate the causes for this increase, future multidisciplinary collaboration is key to understanding the interactions between immunoreactive components in gluten-containing cereals and the human gastrointestinal tract and immune system and to devise strategies for CD prevention and treatment beyond the gluten-free diet. During the last meetings, the Working Group on Prolamin Analysis and Toxicity (Prolamin Working Group, PWG) discussed recent progress in the field together with key stakeholders from celiac disease societies, academia, industry and regulatory bodies. Based on the current state of knowledge, this perspective from the PWG members provides recommendations regarding clinical, analytical and legal aspects of CD. The selected key topics that require future multidisciplinary collaborative efforts in the clinical field are to collect robust data on the increasing prevalence of CD, to evaluate what is special about gluten-specific T cells, to study their kinetics and transcriptomics and to put some attention to the identification of the environmental agents that facilitate the breaking of tolerance to gluten. In the field of gluten analysis, the key topics are the precise assessment of gluten immunoreactive components in wheat, rye and barley to understand how these are affected by genetic and environmental factors, the comparison of different methods for compliance monitoring of gluten-free products and the development of improved reference materials for gluten analysis.

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.

Characterisation and comparison of selected wheat (Triticum aestivum L.) cultivars and their blends to develop a gluten reference material.

The reliability and comparability of gluten analytical results in gluten-free foods is hampered by the lack of reference materials (RM). This is partly caused by the yet incomplete knowledge of the effect of genetic and environmental variability of wheat proteins on immunochemical analyses, which affects the choice of gluten source to be applied for RM production. We investigated the genetic variability and the effect of harvest year on the protein composition of five previously selected wheat cultivars. We also compared the magnitude of these effects on ELISA results to get closer to the question of choosing individual cultivar or a mixture as an RM. Our results proved that the application of a blend for this purpose is advantageous. The candidates were also produced on pilot scale to investigate the feasibility of upscaling. The results of comparison studies showed that the pilot scale blended flour can also be suitable for RM.

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.