"Spanish flu," encephalitis lethargica, and COVID-19: Progress made, lessons learned, and directions for future research.

One hundred years ago, an influenza pandemic swept across the globe that coincided with the development of a neurological condition, named "encephalitis lethargica" for the occurrence of its main symptom, the sudden onset of sleepiness that either developed into coma or gradually receded. Between 1917 and 1920, mortality of the flu was >20 million and of encephalitis lethargica approximately 1 million. For lessons to be learned from this pandemic, it makes sense to compare it with the COVID-19 pandemic, which occurred 100 years later. Biomedical progress had enabled testing, vaccinations, and drug therapies accompanied by public health measures such as social distancing, contact tracing, wearing face masks, and frequent hand washing. From todays' perspective, these public health measures are time honored but not sufficiently proven effective, especially when applied in the context of a vaccination strategy. Also, the protective effects of lockdowns of schools, universities, and other institutions and the restrictions on travel and personal visits to hospitals or old-age homes are not precisely known. Preparedness is still a demand for a future pandemic. Clinical trials should determine the comparative effectiveness of such public health measures, especially for their use as a combination strategy with vaccination and individual testing of asymptomatic individuals. It is important for neurologists to realize that during a pandemic the treatment possibilities for acute stroke and other neurological emergencies are reduced, which has previously led to an increase of mortality and suffering. To increase preparedness for a future pandemic, neurologists play an important role, as the case load of acute and chronic neurological patients will be higher as well as the needs for rehabilitation. Finally, new chronic forms of postviral disease will likely be added, as was the case for postencephalitic parkinsonism a century ago and now has occurred as long COVID.

Back to the future: encephalitis lethargica as an autoimmune disorder?

More than 100 years after its emergence, the exact pathophysiological mechanisms underlying encephalitis lethargica (EL) are still elusive and awaiting convincing and complete elucidation. This article summarizes arguments proposed over time to support or refute the hypothesis of EL as an autoimmune neuropsychiatric disorder triggered by an infectious process. It also provides a critical evaluation of modern cases labeled as EL and a comprehensive differential diagnosis of autoimmune neurological conditions that could mimic EL. The evidence supporting the autoimmune nature of historical EL is sparse and not entirely convincing. It is possible that autoimmune mechanisms were involved in the pathogenesis of this disease as an idiosyncratic response to a yet unidentified infectious agent in genetically predisposed individuals. Although there has been an increase in the incidence of presumed autoimmune encephalomyelitis since the peak of EL pandemics, most evidence does not support an underlying autoimmune mechanism. There are significant differences between historical and recent EL cases in terms of clinical symptomatology, epidemiology, and neuropathological features, suggesting that they are different entities with only superficial similarity. The term "encephalitis lethargica," still frequently used in the medical literature, should not be used for cases occurring at present in the sporadic form. Historical EL should be kept apart from recent EL, as they differ in important aspects.

Beyond the Neurologist: Charles Foix as a Poet and a Playwright.

BACKGROUND: Charles Foix (1882-1927) may be mostly remembered today due to his contributions to vascular neurology and the syndromes that bear his name, such as the Foix-Alajouanine syndrome. However, he also developed a literary career and composed poetry and a vast collection of plays, often dealing with biblical themes or figures from Greek mythology. SUMMARY: His poetry was often inspired by his own experiences during the First World War, in which he was assigned to serve as a medical officer in Greece, becoming enamored with his surroundings and the classical lore. KEY MESSAGES: The authors explore Foix's poetry and drama and their relationship to his overall work as a neurologist, including his wartime experiences.

André-Thomas (1867-1963), Initiator of Neonatal Neurology.

After a brilliant career as a clinician and anatomopathologist, André-Thomas (1868-1963) spent the last 30 years of his life validating the components of neurological examinations of newborns and infants. This novel approach was developed through long examinations of several hundreds of normal and sick children, notably those with anencephaly. By combining his vast knowledge of physiology with the results of his experimental work, André-Thomas built the foundations of a speciality that did not exist before his time: neuropaediatrics. His Études neurologiques (neurological studies), medical in nature but also very literary, echoing his illustrious predecessors of the 19th century, made him a transmitter of knowledge, a man of transition, from the anatomoclinical method of the 19th century to the standardised investigation techniques of the 20th century.

Voices from the past: The pioneering use of the phonograph in neurology.

Since its discovery by the American inventor and industrialist Thomas Alva Edison (1847-1931) in 1877, the phonograph attracted much interest in the field of medicine. This article describes the earliest pioneering examples of the use of the phonograph in neurology. In France, the use of the phonograph for obtaining audio recordings of delusions and speech or language disturbances was first proposed by Victor Maurice Dupont (1857-1910) in 1889 and in Italy by the physician Gaetano Rummo (1853-1917), who had studied at La Salpêtrière under Jean-Martin Charcot (1825-1893). The applicability of the phonograph to the record of speech disturbances was illustrated in England by John Hughlings Jackson (1835-1911) and William Halse Rivers (1864-1922), and by William Hale White (1857-1949) and Cuthbert Hilton Golding-Bird (1848-1939) in 1891. Since then, audio recordings have been used rarely in neurology, a branch of medicine where the visual aspects dominate, to the extent that inspection can be enough to reach a definite clinical diagnosis. In the mid-20th century, the advent of audio and video recordings supplanted audio recordings alone, relegating them to a very marginal role.

What you feel is not always what you've got. Jean Lhermitte (1877-1959) and the phantom limb phenomenon.

Jean Lhermitte (1877-1959), the French neurologist and psychiatrist, is most often associated with the sign he described in three patients with multiple sclerosis, back in 1927. In 1937, Lhermitte analytically studied a series of 28 amputees experiencing phantom limb sensations further to amputations dating between 1891 and 1934. After having described the main clinical characteristics of this unpublished series, we will detail the ideas advanced by Jean Lhermitte regarding the phenomenon of the phantom limb. Lhermitte will use these observations to develop conceptions of consciousness and the body schema encompassing very modern resonances.

"A Great Reinforcing Organ": the Cerebellum According to Silas Weir Mitchell.

This Cerebellar Classic highlights a work by the physician and novelist, Silas Weir Mitchell (1829-1914), a pupil of Claude Bernard and a founding father of American neurology. Published in the aftermath of the American Civil War, the article reported observations on cerebellar physiology based on ablation and tissue freezing experiments in pigeons, rabbits, and guinea pigs. Mitchell communicated his results before the Academy of Natural Sciences of Philadelphia, and proposed a general theory of the cerebellum as an augmenting and reinforcing organ to the cerebrospinal motor system. After reviewing and contrasting previous theories of Flourens and Bouillaud, Mitchell formulated his own theory, which was in line with the views of Rolando and Luys. The theory emphasized the necessity, initially suggested by Brown-Séquard, of distinguishing between phenomena due to loss of function and those due to irritation as a central principle that should guide any physiological research.

Camillo Negro (1861-1927) and the "bulbo-palpebral hyperkinetic phenomenon" in peripheral facial palsy.

Camillo Negro (1861-1927) was a leading Italian neurologist and neuropathologist between the nineteenth and twentieth centuries. He is best known for describing the cogwheel sign in Parkinson disease. In an article published in 1906, Camillo Negro described the "bulbo-palpebral hyperkinetic phenomenon": in peripheral facial paralysis, if the patient is asked to look up, the eyeball deviates outwards and elevates farther on the affected side. Negro thoroughly investigated the neuroanatomic and neurophysiological basis of this phenomenon that gained a certain popularity and was reported in several articles and textbooks. This sign retains some utility in peripheral facial palsy to identify a doubtful or very slight impairment of the upper face muscles, which may otherwise go unnoticed. The interest towards the semiology of peripheral facial palsy was shared by Negro's assistant Giuseppe Roasenda (1879-1959), who in 1933 described the incomplete convergence of the eyeballs in this condition.

Adolph Seeligmüller (1837-1912) and the first graphic illustration of the "toe phenomenon" (later called "Babinski sign") in the medical literature.

The "toe phenomenon" refers to the extension (dorsiflexion) of the great toe, which occurs instead of the normal flexion following stimulation of the foot sole. Its clinical significance was not fully appreciated until Joseph Jules François Félix Babinski (1857-1932) described it in 1896. In 1881, Ernst Strümpell (1853-1925) had described a continuous (tonic) extension of the big toe, a finding that years later the French neurologist Jean-Athanase Sicard (1872-1929) recognized as an equivalent of the "toe phenomenon", also indicating pyramidal tract dysfunction. Previously, this phenomenon had been mentioned in patients only passingly and without providing a picture of it. In 1887, the German neurologist Adolph Seeligmüller (1837-1912) mentioned the tonic extension of the big toe among the characteristic clinical features of spastic infantile hemiplegia-a condition first described by the Austrian physician Moritz Benedikt (1835-1920) in 1868. Seeligmüller incorrectly attributed the tonic extension of the big toe to spastic contracture of the extensor hallucis longus muscle. However, he put great emphasis on this sign and considered it worth being illustrated. Adolph Seeligmüller therefore provided the very first graphic illustration of the (tonic) "toe phenomenon" in the medical literature. Of note, the first photographic illustration of this sign made by Babinski appeared only in 1900, when it had already been adopted by neurologists all over the world.

Camillo Negro (1861-1927) and his method for eliciting the extensor toe sign.

The "toe phenomenon", or extensor toe sign, is characterized by the extension (dorsiflexion) of the great toe elicited by plantar stimulation, and indicates pyramidal tract dysfunction. This phenomenon was first extensively described and studied by Joseph Jules François Félix Babinski (1857-1932), who introduced it in clinical practice. In 1912, the famous Italian neurologist Camillo Negro (1861-1927) proposed a new method of eliciting the extensor toe sign by inviting the patient, lying in bed in dorsal decubitus position, to raise the paretic limb with the leg extended on the thigh. This sign appeared during voluntary effort and could not be elicited by raising the unaffected lower limb. Negro was also the first to investigate the influence of cold upon the appearance of the "toe phenomenon" and to propose the use of (faradic) electrical stimulation to evoke it.

Treatments in Neurology: The Winding Road from 1897 to 2022.

BACKGROUND: For many years, neurology was seen as a purely observational discipline, focused on pathology and with little interest in treatments. SUMMARY: From the creation in 1897 of Monatsschrift für Psychiatrie und Neurologie, the forebear of European Neurology, to nowadays, there have been great changes in the paradigms and concepts of treatments in neurology. We present an overview of the evolution of neurological treatments from 1897 to 2022. KEY MESSAGES: However, the last 125 years have not consisted of constant progress. The exceptional advances made in some diseases (multiple sclerosis or surgical treatment of Parkinson's disease) cannot hide the stagnation in others (certain brain tumors or amyotrophic lateral sclerosis).

Charcot's Anglophilia.

Jean-Martin Charcot was one of the most influential physicians of the nineteenth century and is now rightly considered the father of Neurology. The aim of this paper was to review and describe Charcot's close relationships to Britain and the influence of this particular affinity on his career.

Désiré Bourneville: A Socialist in Charcot's Inner Circle.

Désiré Bourneville was one of Jean-Martin Charcot's most important disciples. His previous works as an alienist allowed him to influence his master's interest in hysteria, which led to the creation of a service regarded as a neurological mecca. During his time under Charcot, Bourneville, a passionate left-wing radical, had to coexist with characters representative of the conservative, bourgeois Parisian society. The aim of this study is to describe Bourneville's life and work, as well as the ambiguity of a progressive man such as him, immersed within the economic and cultural elites.

Albert Pitres: Charcot's Brilliant Student.

Albert Pitres (1848-1928) was an internist, neuropsychiatrist, professor of anatomy, pathology, and histology. He never really had a biography in English. However, the development of neurology and neurosciences in Bordeaux owes a lot to him, as to the psychiatrist Emmanuel Régis (1855-1918). The fact that his career was so closely linked with Charcot (1825-1893) should have secured him a more prominent place in neurology and the history of aphasiology. Pitres went on to co-author clinical and experimental research papers with Charcot that are considered some of the most notable ones among Charcot's publications. Both carried out studies about pathological correlations between cortical lesions and hemiplegia, published series of articles and two major books about neurophysiology of motor control. To convey the atmosphere and the importance of the neurological clinic of Pitres in the heyday, we illustrate this article with unpublished photos of him.

Baron Larrey at the Dawn of Correlative Neuroanatomy.

In 1820, a young soldier was accidentally injured by a splinter of a fencing sword that penetrated through the right orbit into the brain. Examination by the French military surgeon Baron D.-J. Larrey revealed nominal aphasia, right hemiplegia, and monocular temporal hemianopia with an altitudinal component in the right eye only. In this paper, we aimed to reconstruct Larrey's contribution to neurology in the eve of correlative neuroanatomy. Larrey predicted that the blade passed from the roof of the right orbit to graze the root of the right optic nerve at the chiasm and from there, into the vicinity of the left Sylvian fissure. This course was verified posthumously 3 months later. Larrey's previous experience with galvanic currents enabled the adoption of Samuel von Sömmering's idea of regarding the brain as a telegraphing system made of a multitude of galvanic piles sending and receiving messages from distant points. Larrey's description is a very early diligent study of the tracks of penetrating head injuries. It correlates the symptoms with the injured cerebral tissues together with autopsy verification. Here are the beginnings of the construction of human correlative neuroanatomy, which lingered until flourishing in the first decades of the 20th century.

Jean-Alexandre Barré: Babinski's brilliant student.

Guillain-Barré Syndrome, (GBS), is a popular eponym that comes from a paper written in 1916 by Doctors. Guillain, Barré, and Strohl. Its spectrum has been enlarged considerably since the first description of it. Jean Alexandre Barré was a French neurologist, whose name is still widely associated with that of Georges Guillain, (1876-1961). He is also known for the leg manoeuvre. As Joseph Babinski's brilliant student, (1857-1932), we wanted to briefly retrace his biography in order to highlight some of the salient points within it and subjects that are topical for young neurologists today.

Louis Tanquerel des Planches (1810-1862) and the history of discovering lead poisoning in the nervous system.

Louis Tanquerel des Planches (1810-1862) only left us with one significant medical work, his Traité des maladies de plomb ou saturnines (treatise on lead or saturnine diseases), published in 1839. The work served as a reference for diagnosing and treating lead poisoning throughout the second half of the nineteenth century. The word "encephalopathy" that he coined at that time referred to toxic damage to the central nervous system. Whereas for two millennia and for most physicians, lead poisoning was considered lead colic, i.e. paroxysms of abdominal pain, Tanquerel collected seventy-two observations of damage to the central nervous system in workers exposed to lead in Parisian workshops (which no longer exist). He then inventoried and described forms of paralysis, delirium, coma, and convulsions related to lead poisoning. Having no qualms about stepping away from La Charité Hospital where he had treated patients with lead poisoning, he inspected their workplaces and unambiguously presented the deplorable conditions that caused so many patients to die. His "preservative" advice was an initial attempt at medical-social prophylaxis with the goal of helping the working class exposed in workshops without any respect for human life. With support from chemists and pharmacists, Tanquerel showed the presence of lead in brain tissue and thus demonstrated its neurological toxicity as early as 1839. This article is also an opportunity to note the contributions on this topic of some other physicians: François-de-Paule Combalusier (1713-1762), François Victor Mérat de Vaumartoise (1780-1851), Jean-Louis Brachet (1789-1858), Auguste Mirande (1802-1865), Vincent Nivet (1809-1893), Augustin Grisolle (1811-1869), and Ferdinand de Bernard de Montessus (1817-1899).

Percivall Pott (1713-1788) on the curvature of the spine and the French contribution.

Physicians remember the name of the surgeon Percivall Pott (1713-1788) because of the eponym "Pott's disease", described as "paralysis in the lower limbs, which is often accompanied by curvature of the spine". Pott's writings on surgical subjects are far vaster. For example, he described the fracture-dislocation of the ankle, or Pott's fracture, and determined the cause of scrotum cancer in chimney sweeps. He attributed this disease to contact with tar that contaminated the clothing of workers, often very young children because they were small enough to fit into chimney conduits. His work led to the first law addressing the employment of children. After a brief account of Pott's life, this article presents the description of Pott's paraplegia, for which both Jean-Martin Charcot and Yvonne Sorrel-Dejerine paid him homage. The contribution of some of his predecessors and of French contemporaries is highlighted. Pott was also a pioneer in neurosurgery, describing the non-symptomatic interval between cranial trauma and coma and the indication for trepanation to remove a haematoma.

Anglo-French neurological interactions in the 19th and early 20th centuries: Societies and Journals.

We have reviewed seminal interactions between British and French physicians prior to and following the establishment of the Paris and London Schools of Neurology from the mid-19th to the early 20th centuries. Our first article focused on British and French physicians, places and events. In this second part of our review we have examined the interactions between British and French Neurological Societies and Journals, including: (1) The Neurological Society of London founded in 1886, which became the Section of Neurology of the Royal Society of Medicine; (2) The Société de Neurologie de Paris founded in 1899, later renamed as The Société Française de Neurologie; (3) The journal Brain and its precursors and successors; (4) The journal Revue Neurologique and its precursors. We illustrate the constructive influence of Anglo-French interactions on the early development of neurology by the distinguished physicians who were corresponding members respectively of the British and French Neurological Societies and the scientific articles published by French authors in Brain and by British scientists in Nouvelle Iconographie de la Salpêtrière, Archives de Neurologie and Revue Neurologique.

The curious synalgia of Henri Gourdan de Fromentel (1858-1914).

In 1883, Henri Gourdan de Fromentel defended his thesis on an original topic that has not really been studied since. He examined the simultaneous perception of pain in two distinct and distant, but homolateral, areas of the body following a single stimulation on himself. In the discussion he compared his synalgia with other types of synaesthesia that did not involve pain and concluded that it was likely to be of central nervous system origin. After a brief account of Fromentel's life, this article discusses his thesis and a book on the subject he published five years later in the light of current understanding of the phenomenon and the proximity of synalgia and allachaesthesia.