Beasts and Gods: Hippocampal quarrels before memory.

The first description and naming of the hippocampus is usually credited to Arantius (c. 1530 - 1589), whose comparison of the swelling inside the temporal horn of the lateral ventricle to a seahorse (hippocampus) or silkworm (bombyx) was published in the 1587 edition of the Anatomicarum Observationum Liber. However, in the 17th century, the term hippocampus was rarely used and its precise anatomy remained a mystery. The 18th century saw the hippocampus referred to as a wide range of animals and divinities. These terminological issues provoked heated discussions in the French Académie Royale des Sciences, culminating in the seminal description of the hippocampus in the 1780s by Félix Vicq d'Azyr (1748-1794). However, it is striking that no hypothesis concerning the function of the hippocampus was proposed, and its link with memory was not established until the mid-20th century.

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).

J.L. Prévost, Eye Deviation, and Early Steps in Space Lateralization: "Looking At or Away".

Conjugate deviation of the eyes toward side of lesion was recognized over a century ago as a manifestation accompanying hemiplegia, usually of apoplectic origin. While working on the services of Alfred Vulpian and Jean-Martin Charcot, Jean-Louis Prévost sparked international interest in the neurologic sign later named after him. His 1868 thesis represents the first systematic case series of patients with this ocular sign, observed in conjunction with head rotation toward the nonparalyzed side, which he called conjugate deviation (CD) of the eyes. Within a decade, it was uniformly reported in both French and English medical literature. Ipsilesional deviation was the rule for cortical or subcortical paralytic lesions. Contralesional deviation, more rarely seen, signaled lesions of lower brain regions, particularly pontine, or indicated irritative, excitatory effects (as in Jacksonian epilepsy). The sign was recognized to be a valuable diagnostic aid in unilateral cerebral lesions. Centralized control of CD by specific cerebral sites, such as frontal, or occipital, or oculomotor centers, was explored, along with the complex relationship with hemineglect, which interestingly was reported only several decades later. The discovery of intricate oculomotor interconnections and self-space relationships, which play an essential role in CD, owes much to Prévost and his followers.

Clinical Pharmacokinetics and Pharmacodynamics of Desmoteplase.

Desmoteplase is a bat (Desmodus rotundus) saliva-derived fibrinolytic enzyme resembling a urokinase and tissue plasminogen activator. It is highly dependent on fibrin and has some neuroprotective attributes. Intravenous administration of desmoteplase is safe and well tolerated in healthy subjects. Plasma fibrinolytic activity is linearly related to its blood concentration, its terminal elimination half-life ranges from 3.8 to 4.92 h (50 vs. 90 µg/kg dose). Administration of desmoteplase leads to transitory derangement of fibrinogen, D-dimer, alpha2-antiplasmin, and plasmin and antiplasmin complex which normalize within 4-12 h. It does not alter a prothrombin test, international normalized ratio, activated partial thromboplastin time, and prothrombin fragment 1.2. Desmoteplase was tested in myocardial infarction and pulmonary embolism and showed promising results versus alteplase. In ischemic stroke trials, desmoteplase was linked to increased rates of symptomatic intracranial hemorrhages and case fatality. However, data from "The desmoteplase in Acute Ischemic Stroke" Trials, DIAS-3 and DIAS-J, suggest that the drug is well tolerated and its safety profile is comparable to placebo. Desmoteplase is theoretically a superior thrombolytic because of high fibrin specificity, no activation of beta-amyloid, and lack of neurotoxicity. It was associated with better outcomes in patients with significant stenosis or occlusion of a proximal precerebral vessels. However, DIAS-4 was stopped as it might have not reached its primary endpoint. Due to its promising properties, desmoteplase may be added into treatment of ischemic stroke with extension of the time window and special emphasis on patients presenting outside the 4.5-h thrombolysis window, with wake-up strokes and strokes of unknown onset.

Cerebral Hyperperfusion Syndrome and Related Conditions.

Cerebral vasoconstriction is a normal physiological response under determined conditions to preserve a normal cerebral blood flow. However, there are several syndromes, with impaired cerebral autoregulation and cerebral vasoconstriction, not related with infection or inflammation, which share the same radiological and clinical presentation. We review here the cerebral hyperperfusion syndrome and related conditions such as hypertensive encephalopathy, posterior reversible encephalopathy syndrome, and reversible cerebral vasoconstriction syndrome. These syndromes might share the same pathophysiological mechanism with endothelial damage, cerebral vasoconstriction, blood-brain barrier disturbance, cerebral edema, and, occasionally, intracerebral hemorrhage, with fatal cases described in all. Despite knowledge of these syndromes, they still remain unknown to us. Why these entities present in some patients and not in others goes further than the actual understanding of these diseases. We have to consider that a genetic susceptibility and molecular disturbances may be involved. Thus, more studies are needed in order to better characterize such syndromes.

The Merging Tracks of Anosognosia and Neglect.

Anosognosia and hemineglect are among the most startling neurological phenomena identified during the 20th century. Though both are associated with right hemisphere cerebral dysfunction, notably stroke, each disorder had its own distinct literature. Anosognosia, as coined by Babinski in 1914, describes patients who seem to have no idea of their paralysis, despite general cognitive preservation. Certain patients seem more than unaware, with apparent resistance to awareness. More extreme, and qualitatively distinct, is denial of hemiplegia. Various interpretations of pathogenesis are still deliberated. As accounts of its captivating manifestations grew, anosognosia was established as a prominent symbol of neurological and psychic disturbance accompanying (right-hemisphere) stroke. Although reports of specific neglect-related symptomatology appeared earlier, not until nearly 2 decades after anosognosia's inaugural definition was neglect formally defined by Brain, paving a path spanning some years, to depict a class of disorder with heterogeneous variants. Disordered awareness of body and extrapersonal space with right parietal lesions, and other symptom variations, were gathered under the canopy of neglect. Viewed as a disorder of corporeal awareness, explanatory interpretations involve mechanisms of extinction and perceptual processing, disturbance of spatial attention, and others. Odd alterations involving apparent concern, attitudes, or belief characterize many right hemisphere conditions. Anosognosia and neglect are re-examined, from the perspective of unawareness, the nature of belief, and its baffling distortions. Conceptual parallels between these 2 distinct disorders emerge, as the major role of the right hemisphere in mental representation of self is highlighted by its most fascinating syndromes of altered awareness.

The mysteries of hysteria: a historical perspective.

Jean-Martin Charcot started his main work on hysteria around 1870, until his death in 1893. Désiré Bourneville had triggered Charcot's interest in hysteria during his stay as an interne in his department, while Charles Richet's 1875 article on somnambulism was the trigger for Charcot to develop hypnotism. Charcot's collaborators Paul Richer, Georges Gilles de la Tourette, Paul Sollier, Joseph Babinski, Sigmund Freud and Pierre Janet subsequently became most famous in hysteria. In 1908, a "quarrel of hysteria" opposed several of Charcot's pupils, from which Babinski, who had developed the concept of "pithiatism", was considered victorious against Charcot's first successor Fulgence Raymond. There was a surge of interest in hysteria associated with war psycho-neuroses in 1914-1918, and Babinski's pupil Clovis Vincent developed a treatment called torpillage (torpedoing) against war hysteria, associating painful galvanic current discharges with "persuasion". After World War I, the neurological and psychiatric interest in hysteria again faded away, before a renewed interest at the turn of the last century. Contrary to a common view, the modernity of several of Charcot's concepts in hysteria is remarkable, still today, mainly for: (1) his traumatic theory, which encompassed psychological and certain sexual factors several years before Freud; (2) his personal evolution towards the role of emotional factors, which opened the way to Janet and Freud; (3) his claim of specific differences vs. similarities in mental states such as hypnotism, hysteria, and simulation, which has recently been confirmed by functional imaging; and (4) his "dynamic lesion" theory, which now correlates well with recently established neurophysiological mechanisms.

Charcot, Janet, and French Models of Psychopathology.

Jean-Martin Charcot (1825-1893), thanks to his insight as a clinician can be said to be one of the precursors of scientific psychology. Charcot's 30 years of activity at La Salpêtrière hospital display an intellectual trajectory that decisively changed the idea of human psychology by favouring the emergence of two concepts: the subconscious and the unconscious. It was his collaboration with Pierre Janet (1859-1947), a philosopher turned physician, that led to this evolution, relying on the search for hysteria's aetiology, using hypnosis as a method of exploration. Focusing on clinical psychology that was experimental and observational, Janet built a theory of psychic automatism, "the involuntary exercise of memory and intelligence" leading to "independence of the faculties, freed from personal power." From all that came the idea of the subconscious, a functioning as a passive mental mechanism, resulting from a more or less temporary dissociation of previously associated mental content.

Hemineglect and Attentional Dysfunction.

Tracing the history of neglect is intriguing, as diverse terminologies have been used to characterize a multi-factorial disorder with rather startling manifestations. In part, heterogeneous terms may have hinted at distinct subtypes. Thus, different variants of hemi-inattention and neglect relate conceptually, but may be functionally dissociable. Patients with neglect, acting as if the world-space they perceive is full, do not phenomenally experience the omissions or absences so patently obvious to an observer. From the late 19th century, hemi-inattention was described according to its prominent manifestations, visual, bodily or spatial. Since then, diverse terms including imperception, inattention, unilateral visual inattention, unilateral spatial agnosia, and neglect, among others, reflected proposed underlying mechanisms. Major theories presented to account for this curious, even astonishing, neurological disorder, included disruption of body-scheme, perceptual rivalry and extinction, forgetting or amnesia for half the body, and highly nuanced models of distribution of directed spatial attention, and of disrupted perceptual processes. Unlike neurological counterparts, already designated as hemi-syndromes by the first part of the 20th century, not until about 1970 did neglect become so broadly recognized as a syndrome. Earlier, commonalities were identified, features conceptually clustered, and then subtypes were distinguished. Neglect was designated as an overarching term for a class of disorder with distinct subtypes, including visual, motor, extrapersonal, bodily or personal, other somatosensory, and representational. Specificity for modality, chronology, material, and symptom severity was noted. Remarkable clinical, neuropsychological, and behavioral manifestations of hemi-inattention and neglect may involve varying proposed mechanisms of higher cognitive functions, all within a spectrum of clinical disorder. Concepts of connectivity and interaction, neural networks, and functional integration enhance understanding of dysfunction, recovery, and compensation in neglect and inattention. Focus on distinct manifestations clustered under the umbrella of neglect offers a vantage point for examining historical trends in approach to the phenomenon.

Neurology versus Psychiatry? Hallucinations, Delusions, and Confabulations.

Hallucinations, delusions, and confabulations are common symptoms between neurology and psychiatry. The neurological diseases manifesting with such symptoms (dementia, epilepsy, Korsakoff's disease, brain tumors, Parkinson's disease, migraine, right hemisphere stroke and others) would be the key to understand their biological mechanisms, while the cognitive sciences, neuropharmacology and functional neuroimaging would be the tools of such researches. It is possible to understand the perceptive rules of the mind and the mechanisms of the human consciousness based on these symptoms. However, hallucinations and delusions manifest with extraordinary vehemence with psychiatric disorders such as psychosis and schizophrenia, with which there is no evidence of brain lesions. Furthermore, they are subjective symptoms, and they do not have biological markers. Hence, they are prone to high inter-individual variability and depend on other variables (such as education, history of trauma), and are therefore difficult to reduce to unequivocal constructs. Causative mechanisms are probably multiple. For understanding these symptoms, a common framework between neurology and psychiatry is still missing. The psychopathology of French alienists over the 19th century, of S. Freud, and of Henry Ey over the 20th century gave way, in the second half of the 20th century, to the adoption of the DSM and neurosciences, to pursue a pure neurological perspective. However, although psychodynamic models seem nowadays (in a technological era) less influential, detailed clinical evaluations focusing on emotional-cognitive paradigms are probably the only way to lead to new neurobiological researches.

Édouard Manet's Tabes Dorsalis: From Painful Ataxia to Phantom Limb.

Édouard Manet (1832-1883) is considered the "father" of impressionism and even of twentieth century modern art. Manet's genius involved getting away from the classical narrative or historical topics and replacing them by the banality of daily life. Technically, he erased volumes into flat two-dimensional coloured planes, and distorted conventional perspective with often gross brushstrokes intentionally giving an "unfinished" aspect to the work. It is little known that Manet had a very painful second part of his life, due to excruciating limb and chest pains, which developed in parallel with proprioceptive ataxia and gait imbalance. Manet always remained discreet about his private life, and we mainly know that his future wife was his family piano teacher, with whom he had a liaison at the age of 17 years. Later, the great but platonic passion of his life was the painter Berthe Morisot (1841-1895), who married Manet's brother Eugène. In fact, we do not know whether he had a mistress at all, although he had several elegant "flirts" in the mundane and artistic milieu. Thus, while Manet's progressive painful ataxia from the age 40 years yields little doubt on its tabetic origin, how he contracted syphilis at least 15-20 years before will probably remain a mystery. It is fascinating that Manet's daily struggle against pain and poor coordination may have led his art to become one of the most significant of modern times, opening the way to twentieth century avant-gardes, along with another victim of syphilis, Paul Gauguin (1848-1903). Manet never showed any sign of general paresis, and like his contemporary, the writer Alphonse Daudet, his clinical picture remained dominated by paroxysmal pain and walking impairment. Difficult hand co-ordination made him quit watercolour painting, and during the last 2 years of his life he had to focus on small format oil works, the subject of which was nearly limited to modest bunches of fresh flowers, now often considered to be his maturity masterpieces. Having become bedridden, he had to be amputated of one leg, which was developing gangrene, probably associated with ergot overuse. While he died shortly thereafter, we have some witness anecdotes suggesting that he experienced a phantom limb: when Claude Monet (1840-1926) visited him and sat down on his bed, Manet violently shouted that he was sitting on his (absent) leg, which provoked terrible pains. With its facts and mysteries, the subtle interaction between Manet's illness and his work output remains one of the most intriguing stories in the neurology of art.

Joan Miró and Cyclic Depression.

Psychopathology has been closely related with artists. A link between creativity and a tendency to affective disorders has become widely accepted. Several studies have shown that artists suffer disproportionately high rates of mood disorders, particularly manic depression and major depression. The famous twentieth century Spanish artist Joan Miró suffered from depression during the entirety of his life, as was recognized by some authors in private letters. The artist worked using several styles, as well as in ceramics and sculpture. Some of his work reflects the feelings he experienced during the Spanish Civil War and the Second World War. He contributed considerably to the world of art with works such as The Farm as the culminant work of detailism, The Harlequin's Carnival as one of the main expressions of surrealism, the Birth of the World as the precursor of abstract expressionism, or The Dutch Interiors with "mironians" shapes, among others. Whether depression was the inspiration for his work, or his work was the treatment for his depression, will never be clarified. However, he left a great legacy for humanity and his work is admired all over the world.

Dementia and Change of Style: Willem de Kooning - Obliteration of Disease Patterns?

The studies on the relation between artistic production, especially visual art, and brain function gave a basis to the development of neuroesthetics. Most of the information on brain artistic creativity comes from studies on brain disease in well-established visual artists. Brain disease may cause change, dissolution, or emergence of artistic creativity. The visual artistic production may become impaired in individuals with a variety of brain diseases, including focal and generalised disorders of sudden and slowly progressive onset. In addition to that, neurological disorders may add content into visual art production, even becoming the artistic theme. Here, we discuss the particular case of abstract expressionist Willem de Kooning and the evolution of his artistic production in the context of his neurodegenerative illness. The change of de Kooning's artistic style has been the subject of many reviews, and the main focus of this paper is on artistic style across his prolific artistic career in the context of his progressive neurological condition, which he developed in his late years, and his long history of alcohol addiction. There are conflicting data from the literature on the effect of his neurological condition and clear cognitive decline on his artistic output, with preservation of recognition and the quality of his art. Hence, two pertinent questions relate to how he was able to maintain his output despite his cognitive decline, and how his condition could have affected his work.

Louis-Ferdinand Céline: From First World War Neurological Wound to Mythomania.

The writer Louis Ferdinand Céline (1894-1961) developed a personal style which changed twentieth century French literature. As an enlisted soldier in 1912, he was involved in the Great War and his right arm was severely wounded. After the war, he became a medical doctor and a writer who published his first novel, Voyage au bout de la nuit (Journey to the End of the Night), in 1932. In the middle of the 1930s, he began to write anti-Semitic and racist pamphlets and turned to a collaborationist stance with Nazi Germany. After the Second World War, he was declared a national disgrace in France and fled to Denmark. In 1951, he was granted amnesty and went back to France, where he regained fame with his last three novels. Céline was a First World War neurologically wounded soldier who received a severe injury in the right arm leading to a radial nerve paralysis. Furthermore, in his texts and letters, he complained of many symptoms that he considered to be related to the First World War. In reality, to build a heroic image of himself, Céline rewrote his personal First World War history, in particular his war wounds. The aim of this reconstruction was to help him achieve literary fame. At the end of the Second World War, he also used this rewriting to organise his defence when he was accused and tried for collaborationism. Using medical and military archives, Céline's First World War medical mythology is reviewed to distinguish facts from fiction concerning his wound and other war neurological disturbances. We present the history of his radial nerve lesion and surgery, and confirm that Céline was never trepanned. Two other controversial neurological points, his left ear disease and his possible shell shock, are also discussed.

Writers as Shell Shock Witnesses during World War I.

The issue of First World War shell shock has been documented mainly from a medical perspective. Many medical texts dealing with war psychoneuroses and their aggressive treatments, such as electrotherapy, were published during the war. Accounts from shell-shocked soldiers are rare. Nevertheless, shell shock was described from a non-medical point of view by a few writers who had undergone or witnessed this pathology. Their texts deal mainly with the psychiatric forms, the most striking ones, but also with the more common concepts of commotion, emotion and pathological fear. The French philosopher Émile Chartier (1868-1951), alias Alain, described the commotional syndrome from which he suffered. The German writer Ernst Jünger (1895-1998), a brave officer and an example for his men, reported his emotional shock. Some psychiatric forms of shell shock are present in the work of the pacifist writer Jean Giono (1895-1970), the naturalist Maurice Genevoix (1890-1980), who suffered himself from a section of the left median and ulnar nerves, or the British poet Siegfried Sassoon (1886-1967). War hysteria and pathological fear have been described, on several occasions, by Blaise Cendrars (1887-1961) or the German writer Erich Maria Remarque (1898-1970). Electrotherapy has been scarcely reported except by Louis-Ferdinand Céline (1894-1961).