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 origins and early development of the ILAE/IBE/WHO global campaign against epilepsy: Out of the shadows.

The International League Against Epilepsy (ILAE)/International Bureau for Epilepsy (IBE)/World Health Organization (WHO) Global Campaign Against Epilepsy was launched in Geneva and Dublin in the summer of 1997. The second phase of the Campaign was launched by a major event in Geneva, led by WHO Director General Dr. Gro Harlem Brundtland in February 2001. Since then, the Campaign has been gathering momentum around the world culminating in the WHO General Assembly Resolution (WHA 68.20) on Epilepsy in May 2015 supported by 194 countries. Recently, the World Federation of Neurology and other neurological non-governmental organizations (NGOs) have joined forces with the Epilepsy Campaign, leading to the WHO General Assembly Resolution (WHA 73.10) in May 2022 promoting a 10-year Intersectoral Global Action Plan (IGAP) for Epilepsy and Other Neurological Disorders. I was privileged to serve as the first Chairperson of the Global Campaign Against Epilepsy and this year all my documents and correspondence relating to the Campaign have been delivered to the Wellcome Collection in London. These are the basis for this detailed account of the origins and early development of the Campaign. I describe the events leading to the birth of the concept, planning for the Campaign, the launch, development, and the achievements of phase one. This first phase focused on awareness raising, education, and involvement, especially within WHO, ILAE, and IBE, including a series of five Regional Public Health meetings and Declarations on Epilepsy. In 1999, the WHO raised the status of the Campaign to the highest level, the first ever for a Non-Communicable Disease, resulting in the high profile launch of phase two in 2001, paving the way to the continuing global momentum and achievements, including the 2015 and 2022 WHO Resolutions.

Improvement Initiative to Develop and Implement a Tool for Detecting Drug-Drug Interactions During Oncology Clinical Trial Enrollment Eligibility Screening.

OBJECTIVES: Screening subjects for drug-drug interactions (DDIs) before enrollment in oncology clinical trials is integral to ensuring safety, but standard procedures or tools are not readily available to screen DDI in this setting. Our objectives were to develop a DDI screening tool for use during oncology clinical trial enrollment and to test usability in single-center and multicenter pilot studies. METHODS: A multistage approach was used for this quality improvement intervention. Semistructured interviews with individuals responsible for DDI screening were conducted to develop a prototype tool. The tool was used for screening DDI in subjects enrolling in National Clinical Trials Network trials of commercially available agents during a single-center 3-month pilot. Improvements were made, and a 3-month multicenter pilot was conducted at volunteer SWOG Cancer Research Network sites. Participants were surveyed to determine tool usability and efficiency. RESULTS: A tool was developed from semistructured interviews. A critical feature was reporting which medications had specific pharmacokinetic and pharmacodynamic characteristics including transporter and cytochrome P450 substrates, inhibitors, or inducers and QT prolongation. In the 12-site study, average (SD) DDI screening time for each patient decreased by 15.7 (10.2) minutes (range, 3-35 minutes; P < 0.001). Users reported the tool highly usable, with >90% agreeing with all positive usability characterizations and disagreeing with all negative complexity characterizations. CONCLUSIONS: A DDI screening tool for oncology clinical trial enrollment was created and its usability confirmed. Further testing with more diverse investigator sites and study drugs during eligibility screening is warranted to improve safety and data accuracy within clinical trials.

Epilepsy and Neuroscience: Evolution and Interaction.

Neuroscience is a relatively new and fashionable word that emerged in the 1950s in several countries, including the UK, to describe a multidisciplinary clinical and laboratory approach to the study of the brain, mind, and neuropsychiatric disorders. However collaborative study of neurological and psychiatric disorders can be traced to the 17th century with roots in antiquity. I describe the evolution of our understanding of epilepsy beginning with the first detailed clinical descriptions, associated with supernatural theories, in Babylonian medicine in the second millennium BC. Interest in natural causation arose in the Greco-Roman period when it was first suggested that "the sacred disease" was a disorder of the brain. However, this theory did not take root until the 17th and 18th centuries AD when epilepsy began to be separated from other "convulsive" diseases, including hysteria. In the 19th century developments in neuropathology and our understanding of cortical localization led to the much-debated separation of idiopathic from symptomatic epilepsy which continues to influence international classifications of seizures and epilepsies. Also in the 19th century, the concept of seizures as electrical discharges in the brain evolved, reinforced in the 20th century by the discovery of the electroencephalogram. For many reasons, people with epilepsy have experienced a high incidence of cognitive and psychosocial disorders. Epilepsy, which is a global problem, has, therefore, remained a bridge between neurology and psychiatry. Furthermore, the study of epilepsy continues to shed light on brain function and other neuropsychiatric disorders.

Valproate and folate: Congenital and developmental risks.

Increasing awareness of the congenital and developmental risks associated with the use of sodium valproate (VPA) has led to recent European guidelines designed to avoid the use of this drug in pregnancy if effective alternative treatments are available. In the general population, it is well established that periconceptual folic acid reduces the risk of neural tube defects (NTDs) and possibly other congenital abnormalities. We here review the evidence 1) that VPA interferes with one-carbon metabolism, including the transport of methylfolate into the brain and the placenta by targeting folate receptors; 2) that VPA effects on the folate metabolic system contribute to congenital and developmental problems associated with VPA exposure; and 3) that genetic factors, notably polymorphisms related to one-carbon metabolism, contribute to the vulnerability to these VPA-induced risks. Based on these facts, we propose that the standard periconceptual use of 400 µg of folic acid may not adequately protect against VPA or other antiepileptic drug (AED)-induced congenital or developmental risks. Pending definitive studies to determine appropriate dose, we recommend up to 5 mg of folic acid periconceptually in at-risk women with the caveat that the addition of supplementary vitamin B12 may also be prudent because vitamin B12 deficiency is common in pregnancy in some countries and is an additional risk factor for developmental abnormalities.

The earliest experimental convulsions by Joseph Priestley in 1766 friendship with Benjamin Franklin.

In 1766, Joseph Priestley (1733-1804) was the first to systematically demonstrate the universal convulsive effect of an electrical discharge applied to the head of all the several species studied. We here republish his overlooked experiments, which often resulted in death, and which ante date the scientific studies of the electrical functions of the brain, the role of "discharges" in seizures, and experimental epilepsy by about a century. Priestley's studies of electricity were influenced by those of Benjamin Franklin (1706-1790), who became a good friend during Franklin's prolonged period in London between 1757 and 1775. Both were elected Fellows of the Royal Society and both were awarded the Copley Medal of that Society. Priestley's experiments are relevant to the history of epilepsy and neuropsychiatry, and to the modern study of sudden unexplained death in epilepsy (SUDEP).

Hysteria in ancient civilisations: A neurological review: Possible significance for the modern disorder.

The word hysteria originated in the Corpus Hippocraticum (c420 BCE) as a natural explanation for a variety of diseases in women linked in the Greco-Roman mind to an animate or inanimate womb, but which in the last five centuries has evolved to describe an elusive disorder of brain ±â€¯mind in men and women, currently referred to by neurologists as "functional neurological disorder". The Babylonians, Assyrians and Egyptians had no knowledge of brain or psychological function. Babylonian and Assyrian descriptions of disease and behaviour include only rare examples suggestive of modern hysteria. An earlier suggestion that the Greek concept of hysteria was transmitted from Egypt is not supported by recent evidence. The Greco-Roman civilisations had some knowledge of neuroanatomy, but little of nervous system function, conceived in terms of humors. The examples cited here suggestive of modern hysteria are relatively infrequent and fragmentary. The most plausible are attempts to separate the "sacred disease" from other causes of loss of consciousness. The great achievement of Greco-Roman medicine was in introducing natural causation, including causation linked to the womb, rather than gods or evil spirits. Nevertheless medicine, magic and religion have remained intertwined to varying degrees in all cultures up to the present time, despite the growth of modern scientific medicine. The study of hysteria in ancient civilisations adds interesting insight into the evolution of thinking about brain, psyche, mind and self. Babylonian and Egyptian medical and behavioural descriptions are based on observation. Greek and Roman accounts include some subjective aspects, probably linked to early attempts to understand identity, the psyche, intellectual and emotional functions. The great philosophical debate whether the latter resided in the head/brain (Plato) or the heart (Aristotle) has only been settled in the last few centuries, during which hysteria also became linked to brain ±â€¯mind. Our more recent increasing knowledge of brain function has also been accompanied by increasing interest in subjective feelings, thoughts, the inner life and subconscious mechanisms, suggesting we may have become more self-aware than in earlier civilisations, which in turn may perhaps influence the clinical presentation of hysteria. The study of hysteria may be one of the keys to a greater understanding of the relationship between brain and mind.

Yorkshire's influence on the understanding and treatment of mental diseases in Victorian Britain: The golden triad of York, Wakefield, and Leeds.

In the late-eighteenth and nineteenth centuries, a more humane approach to the care of the insane in Britain was catalyzed in part by the illness of King George III. The Reform Movement envisaged "moral" treatment in asylums in pleasant rural environments, but these aspirations were overwhelmed by industrialization, urbanization, and the scale of the need, such that most asylums became gigantic institutions for chronic insanity. Three institutions in Yorkshire remained beacons of enlightenment in the general gloom of Victorian alienism: the Retreat in York founded and developed by the Quaker Tuke family; the West Riding Lunatic Asylum in Wakefield led by Sir James Crichton-Browne, which initiated research into brain and mental diseases; and the Leeds Medical School and Wakefield axis associated with Sir Thomas Clifford Allbutt, which pioneered teaching of mental diseases and, later, the first Chair of Psychiatry. Three other Yorkshiremen who greatly influenced nineteenth-century "neuropsychiatry" in Britain and abroad were Thomas Laycock in York and Edinburgh, and Henry Maudsley and John Hughlings Jackson in London.

The origins of the British Neuroscience Association.

I describe the origins of the British Neuroscience Association (BNA) based on new documents which I have discovered. The foundation of the Brain Research Association (BRA) on February 23rd 1968 was influenced by IBRO, notably its two UK Council members, and by many UK neuroscientists, especially the London-based Black Horse Group. The BRA changed its name to the BNA in 1996. The documents are in the Wellcome Trust Archives.