Torben Fog - A Danish pioneer in a multi-faceted spectrum of multiple sclerosis research.

Torben Fog was committed to multiple sclerosis (MS) research for more than four decades, starting before the defence of his thesis in 1948 and lasting until his death in 1987. His research was multi-facetted, making him one of the great pioneers in the study of essential parts of the pathology, immunology and treatment of MS. He has contributed with meticulous studies of the MS plaques, documenting the perivenous distribution of plaques in the spinal cord. He constructed a scoring system for the disability in MS and used a computer programme to calculate a total neurological deficit. Together with his co-workers, Fog in 1972 was the first to report the association between MS and the human leukocyte antigen system. Fog can be considered as the father of immunomodulatory therapy in MS, treating MS patients with the first transfer factor, and as early as 1980, he was the first to treat MS with intramuscular natural interferon.

Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations.

Multiple sclerosis (MS) is a neuro-inflammatory and neurodegenerative disease that is most prevalent in Northern Europe. Although it is known that inherited risk for MS is located within or in close proximity to immune-related genes, it is unknown when, where and how this genetic risk originated1. Here, by using a large ancient genome dataset from the Mesolithic period to the Bronze Age2, along with new Medieval and post-Medieval genomes, we show that the genetic risk for MS rose among pastoralists from the Pontic steppe and was brought into Europe by the Yamnaya-related migration approximately 5,000 years ago. We further show that these MS-associated immunogenetic variants underwent positive selection both within the steppe population and later in Europe, probably driven by pathogenic challenges coinciding with changes in diet, lifestyle and population density. This study highlights the critical importance of the Neolithic period and Bronze Age as determinants of modern immune responses and their subsequent effect on the risk of developing MS in a changing environment.

Ancient DNA ties modern diseases to ancestry.

Among Europeans, risk of multiple sclerosis rises with genes from Bronze Age Yamnaya herders.

BCG turns 100: its nontraditional uses against viruses, cancer, and immunologic diseases.

First administered to a human subject as a tuberculosis (TB) vaccine on July 18, 1921, Bacillus Calmette-Guérin (BCG) has a long history of use for the prevention of TB and later the immunotherapy of bladder cancer. For TB prevention, BCG is given to infants born globally across over 180 countries and has been in use since the late 1920s. With about 352 million BCG doses procured annually and tens of billions of doses having been administered over the past century, it is estimated to be the most widely used vaccine in human history. While its roles for TB prevention and bladder cancer immunotherapy are widely appreciated, over the past century, BCG has been also studied for nontraditional purposes, which include (a) prevention of viral infections and nontuberculous mycobacterial infections, (b) cancer immunotherapy aside from bladder cancer, and (c) immunologic diseases, including multiple sclerosis, type 1 diabetes, and atopic diseases. The basis for these heterologous effects lies in the ability of BCG to alter immunologic set points via heterologous T cell immunity, as well as epigenetic and metabolomic changes in innate immune cells, a process called "trained immunity." In this Review, we provide an overview of what is known regarding the trained immunity mechanism of heterologous protection, and we describe the current knowledge base for these nontraditional uses of BCG.

Antigen-Specific Treatment Modalities in MS: The Past, the Present, and the Future.

Antigen-specific therapy for multiple sclerosis may lead to a more effective therapy by induction of tolerance to a wide range of myelin-derived antigens without hampering the normal surveillance and effector function of the immune system. Numerous attempts to restore tolerance toward myelin-derived antigens have been made over the past decades, both in animal models of multiple sclerosis and in clinical trials for multiple sclerosis patients. In this review, we will give an overview of the current approaches for antigen-specific therapy that are in clinical development for multiple sclerosis as well provide an insight into the challenges for future antigen-specific treatment strategies for multiple sclerosis.

History of Multiple Sclerosis in Iran.

Iran is a great country with a long history of civilization and medicine. Following the increase in the prevalence of multiple sclerosis (MS), Iranian scientists and physicians started considering this disease and its outcomes in Iran. The first MS paper published by Iranian scientists dates back to 1963, when a case of hereditary spastic ataxia mimicking MS was reported. With the cooperation of his colleagues, Prof. Jamshid Lotfi conducted the first MS-related paper. The Iranian MS Society was established in 1998 in Iran, and is currently a member of the MS International Federation (MSIF). Progressively, after the scientific development of Iranian universities and recognizing the importance of the disease, the first specialized MS ward was established in Sina hospital by Prof. Mohammad Ali Sahraian and was followed by the establishment of the first MS research center. MS Society is presently quite active and the Iranian MS congress is annually held in one of the Iranian universities to review the most recent achievements in the field of the disease. The present study aims to illustrate the history of the efforts made on the way, and attempts to introduce the people who took significant steps in this regard.

Mi esclerosis múltiple y yo. Una experiencia de crecimiento personal a través de la escritura / My multiple sclerosis and me: a personal growth experience through writing

En los últimos años, la literatura científica ha mostrado un creciente interés por los factores psicosociales que acompañan e influyen en la enfermedad física, así como por las experiencias de cambio personal que tienen lugar tras el diagnóstico de una enfermedad grave. El objetivo de este trabajo es mostrar una experiencia particular de crecimiento personal en la enfermedad crónica y describir los factores que en este caso han contribuido al proceso. Para ello se ha utilizado el método biográfico, obteniéndose el relato a partir de una entrevista en profundidad. En este relato biográfico se describe, en primera persona, la experiencia de una joven paciente de esclerosis múltiple y cómo la escritura expresiva y el apoyo incondicional de sus seguidores en redes sociales, le ayudaron a poner en marcha un imparable y auténtico proceso de crecimiento post traumático que ha desembocado en la publicación de su primer libro

In recent years, scientific literature have shown a growing interest in the psychosocial factors surrounding physical illness, as well as in personal change experiences that take place after the diagnosis of a serious illness. The aim of this paper is to show a particular experience of personal growth in chronic disease and describe the factors that have contributed to this process. To this end, the biographical method of the qualitative methodology has been used, obtaining the story from an in-depth interview. This story, narrated in first person, describes the experience of a young patient with multiple sclerosis, and how expressive writing and unconditional support of her followers in social networks helped her initiate an unstoppable and genuine process of post traumatic growth that has led to the publication of her first book

From Charcot's descriptions to the current understanding of neuropsychiatric symptoms in multiple sclerosis.

Neuropsychiatric disorders in multiple sclerosis have been known since the original clinicopathological description by Charcot in the late nineteenth century. Charcot, in the last decades of his life, became involved in the field of neuropsychiatry. This produced a battle between rival schools in the era that still echoes to this day. Charcot's intuition, including the line of thought of Babinski, one of his most famous disciples, was that there was a connection between mood disorders and many of the diseases of the nervous system. Medicine's concern with establishing a relationship between mood disorders and disease stems from the ancient and middle ages with references found in the Hippocratic doctrine. However, it was only in the second half of the nineteenth and early twentieth century, with Charcot's discoveries, that this discussion was established in a structured way, laying the foundations of neuropsychiatry.

The two lives of neurologist Helmut J. Bauer (1914-2008): Renowned MS specialist and National Socialist.

In 2008, the internationally renowned neurologist and university professor Helmut Johannes Bauer died at the age of 93 years. In the numerous obituaries and tributes to him, the years between 1933 and 1945 are either omitted or simplified; the Nazi past of Helmut Bauer has hardly been explored. Based on original documents dating from the Third Reich and the early Federal Republic of Germany as well as relevant secondary writings, Bauer's life before 1945 was traced to gain knowledge of his exact activities and tasks during the Second World War. Bauer was actively involved in Nazi crimes. He was a member of the so-called Künsberg special command of the SS and also worked in a prominent position at the Institute for Microbiology as well as for the Foreign Department of the Reich Physicians' Chamber. After World War II, Bauer underwent denazification and, like many others, was able to pursue his further medical career undisturbed, building on the contacts he had already made during the Nazi period.

From Charcot's descriptions to the current understanding of neuropsychiatric symptoms in multiple sclerosis / Das descrições de Charcot à compreensão atual dos sintomas neuropsiquiátricos na esclerose múltipla

ABSTRACT Neuropsychiatric disorders in multiple sclerosis have been known since the original clinicopathological description by Charcot in the late nineteenth century. Charcot, in the last decades of his life, became involved in the field of neuropsychiatry. This produced a battle between rival schools in the era that still echoes to this day. Charcot's intuition, including the line of thought of Babinski, one of his most famous disciples, was that there was a connection between mood disorders and many of the diseases of the nervous system. Medicine's concern with establishing a relationship between mood disorders and disease stems from the ancient and middle ages with references found in the Hippocratic doctrine. However, it was only in the second half of the nineteenth and early twentieth century, with Charcot's discoveries, that this discussion was established in a structured way, laying the foundations of neuropsychiatry.

RESUMO Os distúrbios neuropsiquiátricos na esclerose múltipla são conhecidos desde a descrição clínico-patológica original de Charcot no final do século XIX. Charcot nas últimas décadas de sua vida se envolveu no campo da neuropsiquiatria. Isso produziu uma batalha de escolas rivais na época que ainda ecoa até hoje. A intuição de Charcot, incluindo a linha de pensamento de Babinski, um de seus discípulos mais famosos, foi a teoria correta da conexão entre os transtornos do humor e muitas das doenças do sistema nervoso. A preocupação da Medicina em estabelecer uma relação entre transtornos do humor e doenças vem das idades antiga e média, com referências encontradas na doutrina hipocrática. No entanto, foi apenas na segunda metade do século XIX e início do século XX que, com as descobertas de Charcot essa discussão foi realizada de maneira estruturada, estabelecendo os fundamentos da neuropsiquiatria.

The Gray Degeneration of the Brain and Spinal Cord: A Story of the Once Favored Diagnosis With Subsequent Vessel-Based Etiopathological Studies in Multiple Sclerosis.

In 1857, French-Austrian psychiatrist Bénédict Augustin Morel (1809-1873) published his infamous though highly successful Traité des dégénérescences physiques, intellectuelles et morales de l'espèce humaine, which was fully dedicated to the social problem of "degeneration" and its psychiatric and neurological underpinnings. European psychiatrists, neurologists, and pathologists integrated Morel's approach into their neuropsychiatric theories and searched for the somatic and morphological alterations in the human brain, as did the versatile pupil of Rudolph Virchow (1821-1902), Georg Eduard von Rindfleisch (1836-1908), in his Lehrbuch der pathologischen Gewebelehre (1867). This can be seen as a starting point of research into the vascular genesis of "multiple sclerosis" by observing that the changes of blood vessels and nerve elements could be the result of inflammation and increased blood flow. We examine the waxing and waning of a 19th century diagnostic condition, which fell out of favor and resurfaced during the 20th century.

Neuroimmunology - the past, present and future.

Neuroimmunology as a separate discipline has its roots in the fields of neurology, neuroscience and immunology. Early studies of the brain by Golgi and Cajal, the detailed clinical and neuropathology studies of Charcot and Thompson's seminal paper on graft acceptance in the central nervous system, kindled a now rapidly expanding research area, with the aim of understanding pathological mechanisms of inflammatory components of neurological disorders. While neuroimmunologists originally focused on classical neuroinflammatory disorders, such as multiple sclerosis and infections, there is strong evidence to suggest that the immune response contributes to genetic white matter disorders, epilepsy, neurodegenerative diseases, neuropsychiatric disorders, peripheral nervous system and neuro-oncological conditions, as well as ageing. Technological advances have greatly aided our knowledge of how the immune system influences the nervous system during development and ageing, and how such responses contribute to disease as well as regeneration and repair. Here, we highlight historical aspects and milestones in the field of neuroimmunology and discuss the paradigm shifts that have helped provide novel insights into disease mechanisms. We propose future perspectives including molecular biological studies and experimental models that may have the potential to push many areas of neuroimmunology. Such an understanding of neuroimmunology will open up new avenues for therapeutic approaches to manipulate neuroinflammation.

150th anniversary of clinical description of multiple sclerosis: Leopold Ordenstein's legacy.

The clinical features of multiple sclerosis were first defined in detail and with pathologic confirmation in a medical thesis published at the Salpêtrière, Paris, in 1868. The author, Leopold Ordenstein (1835-1902), a German physician, analyzed cases collected by his mentor, Jean-Martin Charcot (1825-1893). The 2 clinician-scientists described the characteristic symptoms, predisposing age, and pathologic features of the disease, and emphasized the clear delineation from other chronic progressive disorders, especially paralysis agitans. The latter was referred to as Parkinson disease by William Sanders in 1865 and adopted by Désiré-Magloire Bourneville on behalf of Charcot in 1875. This essay commemorates the 150th anniversary of the publication of the pioneering work of Leopold Ordenstein and Jean-Martin Charcot.