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Review: Volume 56 - First World War

Review: Volume 56 - First World War

During the opening four months of the First World War no fewer than forty-six soldiers from the British and Commonwealth armies were awarded the Victoria Cross, Britain's highest award for gallantry. In a series of biographies, Gerald Gliddon examines the men and the dramatic events that led to the award of this most coveted of medals and explores the post-war experiences of those who survived. These men, ordinary soldiers from widely differing social backgrounds, acted with valour above and beyond the call of duty. Their stories and experiences offer a fresh perspective on the opening stages of the 'war to end wars'.


Review: Volume 56 - First World War - History

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Explore the OLL Collection: Images of Liberty and Power Encyclopedic Liberty and Industry

This illustrated essay explores some images of "liberty" and "industry" from Diderot’s Encyclopédie, ou Dictionnaire raisonné des sciences, des arts et des métiers (Encyclopaedia, or a Systematic Dictionary of the Sciences, Arts, and Crafts) (1751-1772). They have been taken from Liberty Fund’s anthology of articles, Encyclopedic Liberty: Political Articles in the Dictionary of Diderot an.


Review: Volume 56 - First World War - History

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The International History of the US Suffrage Movement

Figure 1. Sarah Parker Remond, ca. 1865. This portrait was taken while Remond was in England, the year before she added her name to John Stuart Mill’s petition for woman suffrage.

Albumen print, Peabody Essex Museum, Gift of Miss Cecelia R. Babcock, PH322. Courtesy of Peabody Essex Museum, Salem, MA.

The history of the US woman suffrage movement is usually told as a national one. It begins with the 1848 Seneca Falls convention follows numerous state campaigns, court battles, and petitions to Congress and culminates in the marches and protests that led to the Nineteenth Amendment. This narrative, however, overlooks how profoundly international the struggle was from the start. Suffragists from the United States and other parts of the world collaborated across national borders. They wrote to each other shared strategies and encouragement and spearheaded international organizations, conferences, and publications that in turn spread information and ideas. Many were internationalist, understanding the right to vote as a global goal.

Enlightenment concepts, socialism, and the abolitionist movement helped US suffragists universalize women’s rights long before Seneca Falls. They drew their inspiration not only from the American Revolution, but from the French and Haitian Revolutions, and later from the Mexican and Russian Revolutions. Many were immigrants who brought ideas from their homelands. Others capitalized on the Spanish-American War and the First World War to underscore contradictions between the United States’ growing global power and its denial of woman suffrage. A number of women of color used the international stage to challenge US claims to democracy, not only in terms of women’s rights but also in terms of racism in the United States and in the suffrage movement itself. The complex international connections and strategies that suffragists cultivated reveal tensions in feminist organizing that reverberated in later movements and are instructive today.

These multiple, and sometimes conflicting, international strands worked in synergy, bolstering the suffrage cause and expanding the women’s rights agenda. The resources that women shared with each other across national borders allowed suffrage movements to overcome political marginalization and hostility in their own countries. [1] A radical challenge to power, the US movement for women’s voting rights required transnational support to thrive.

Abolitionism and the Transnational Origins of Women’s Rights
Although the American Revolution and Mary Wollstonecraft’s Vindication of the Rights of Woman (1792), which circulated in the United States, activated discussion of women’s rights, it was the transatlantic crucible of abolitionism that truly galvanized the US women’s rights movement. [2] The antislavery movement, which Frederick Douglass called “peculiarly woman’s cause,” provided broad ideals of “liberty” as well as key political strategies that suffragists would use for the next fifty years—the mass petition, public speaking, and the boycott. Transatlantic networks of organizations, conferences, and publications drove abolitionism. Women in the United States looked to their British sisters, who in 1826 made the first formal demand for an immediate rather than gradual end to slavery.

Boston reformer and African American abolitionist Maria Stewart , one of the first US women to publicly call for women’s rights before a mixed-race and mixed-sex audience, embraced a diasporic vision of freedom when she asked in 1832, “How long shall the fair daughters of Africa be compelled to bury their minds and talents beneath a load of iron pots and kettles?” [3] Her vision of rights for African American women, specifically, in the face of economic marginalization, segregation, and slavery, drew upon universal rights that she found expressed not only in the US Constitution and Declaration of Independence but in the French Declaration of the Rights of Man and the Haitian Revolution, the largest slave uprising, from 1791 to 1804. [4]

Figure 2. The WCTU’s global vision of suffrage, as well as the connections it drew between suffrage, domesticity, and temperance are illustrated in this cover of the Union Signal, the official organ of the US WCTU, March 17, 1921. The hostility that Stewart and other female abolitionists faced for overstepping boundaries of female propriety by speaking out in public threw into sharp relief that, as abolitionist Angelina Grimké put it, “the manumission of the slave and the elevation of the woman” should be indivisible goals. [5] At the 1837 First Anti-Slavery Convention of American Women, an interracial group of two hundred women called for women’s rights. When Elizabeth Cady Stanton , Lucretia Mott , and other female delegates were excluded from the 1840 World Antislavery Congress in London, Stanton hatched the idea for a separate women’s rights convention.

The resulting 1848 Seneca Falls Convention and its demands for women’s rights were only possible because of abolitionists’ groundwork and the broad meanings of emancipation flourishing in the United States and in Europe, where revolutions had broken out that year. Stanton’s idea to include the right to vote in the convention’s Declaration of Sentiments was directly inspired by calls for universal suffrage made by British Chartists, the first mass working-class movement in England. [6] Quaker minister and abolitionist Lucretia Mott explicitly connected the Declaration to the 1848 abolition of slavery in the French West Indies, opposition to the US war with Mexico, and Native American rights. She and Stanton also found models in the matrilineal communities of the Seneca people, in which women held political power. [7] The right to vote proved to be the convention’s most controversial demand, and abolitionist Frederick Douglass was one of its most avid proponents.

The right to vote became key to the many US women’s rights conventions that Seneca Falls set into motion, inspiring and drawing on the support of women in Europe and elsewhere, including immigrant women in the United States. In 1851, from Paris jail cells, revolutionary women’s rights activists cheered US women’s activism. In March 1852, German immigrant and socialist Mathilde Anneke started the first women’s rights journal in the United States published by a woman, the Deutsche Frauen-Zeitung. After the Prussian victory over Germany she had fled to the United States, where she became a friend of Stanton and Susan B. Anthony. [8] Polish-born immigrant and abolitionist Ernestine Rose expressed her global vision for suffrage in 1851: “We are not contending for the rights of women in New England, or of old England, but of the world.” [9]

Such ideas resonated with Sarah Parker Remond, whose life reflects the overlapping transnational abolitionist and woman suffrage movements. In 1832 she helped found the first female antislavery group in Salem, Massachusetts . In 1859, while on an antislavery speaking tour in England, Remond reported, “I have been received here as a sister by white women for the first time in my life. . . . I have received a sympathy I never was offered before.” [10] For Remond, transnational connections became a concrete way to escape racism in the United States. She settled permanently in Italy, where she became a physician. In 1866, Remond affixed her name to John Stuart Mill’s petition to the British Parliament for woman suffrage. [11] (Figure 1)

Figure 3. Teresa Villarreal, cover of El Obrero (San Antonio, TX), November 17, 1910. In 1909, Villareal started this publication to enlist women and men in the revolutionary cause and new social order. The Mexican Revolution and working-class demands infused her calls for woman suffrage in the US.

Courtesy of Arte Público Press, University of Houston, Houston, TX.

Transnational Organizing and “Global Sisterhood”
Transnational connections initiated by the nineteenth-century abolitionist movement only grew in the following decades. After construction of the first t ransatlantic telegraph lines in the 1860s, communications, travel, and transnational print culture helped produce the first international organizations for women’s rights that drew significantly on US women: the World’s Woman’s Christian Temperance Union (WCTU), founded in 1884 by US temperance leader Frances Willard the International Council of Women (ICW), founded in 1888 by Stanton and Anthony the International Woman Suffrage Alliance (IWSA, later renamed the International Alliance of Women), founded in 1904 and presided over by Carrie Chapman Catt (then-president of the National American Woman Suffrage Association) and Women’s International League for Peace and Freedom (WILPF), founded by US social settlement worker Jane Addams in 1915. [12]

Alongside each organization’s particular focus—international arbitration, universal disarmament, temperance, married women’s civil rights, anti-trafficking of women, equal pay for equal work, among others—a global goal of women’s political equality drove them. [13] These organizations connected women across the lines of nation, culture, and language and had overlapping memberships. [14] They hosted international conferences, and they helped spearhead publications such as the IACW’s Jus Sufffragii and the ICW’s Bulletin, which shared information about suffrage organizing in Asia, Latin America, Europe, and other parts of the world.

Of the four, the WCTU inspired the most dramatic grassroots suffrage activism, becoming the largest women’s organization in the world, with over forty national affiliates. An outgrowth of the US Woman’s Christian Temperance Union (1874), the WCTU argued that women could use their vote to promote temperance and end men’s alcohol-infused violence. The organization transformed the goal of woman suffrage into a legible and compelling one for large numbers of women. [15] Spearheading the first organized suffrage efforts in the white British colonies of South Africa, New Zealand, and South Australia, the WCTU was responsible for the world’s first national suffrage victory in New Zealand in 1893, and in Australia in 1902. [16] (Figure 2)

Although these groups spoke of “global sisterhood,” their memberships were predominantly Anglo-American and European, and their publications usually only published in French, English, and German, in spite of demands to expand beyond these languages from women in Spanish-speaking countries and other parts of the world. [17] These international groups generally marginalized or excluded, and in the WCTU’s case segregated, US women of color.

These groups often reflected what historians have called “imperial feminism”—a belief that white, Western women will “uplift” women in “uncivilized” parts of the world. [18] This logic went hand in hand with some suffrage efforts. WCTU missionaries in Hawai'i who sought to secure woman suffrage there in the 1890s, allied with white US business and military interests establishing imperial control over the island. [19] Suffragists also demanded the vote in the United States’ imperial acquisitions from the 1898 Spanish-American War—the Philippines , Puerto Rico , and Cuba—both as part of a civilizing mission and to force discussion of a federal suffrage amendment in the United States . [20] Meanwhile, while celebrating early suffrage victories within the western United States in the same period, most white suffragists overlooked the fact that these states denied the right to vote accorded native-born white women to many Asian American, Mexican American, and Native American women. [21]

African American suffragists powerfully critiqued Anglo-American dominance on the international stage and within the US suffrage movement as they made important contributions to it. They also continued to connect global ideals of “freedom” with local women’s rights issues, expanding the international agenda to address such goals as universal suffrage for men and women, anti-lynching, and education. Former abolitionist Frances Ellen Watkins Harper , a pivotal African American civil rights and women’s rights leader, spoke at the 1888 founding of the ICW and oversaw the formation of many “colored WCTU” groups that contributed to school suffrage victories in several states in the 1890s. [22] On a speaking tour in England, the anti-lynching activist Ida B. Wells brought global attention to WCTU president Frances Willard’s failure to defend African American men lynched on false rape accusations. [23] Wells went on to found the most vital African American woman suffrage group in the country, the Alpha Suffrage Club, in Chicago, and at the 1913 suffrage March on Washington, she refused to be relegated to the back of the procession, reserved for African American women. In 1904, Mary Church Terrell , the first president of the National Association of Colored Women, spoke in fluent German at the ICW meeting in Berlin, pointing out that a global women’s rights agenda must include attention to Black women’s unequal access to many rights, including education and employment. Newspapers in Germany, France, Norway, and Austria lauded her speech. [24]

Figure 4. Starting in 1915, “America First” was a slogan used by those who wanted to keep the US out of WW I. In 1917, when this cartoon graced the cover of the National Woman’s Party organ, the Russian Revolution and its promise of equal rights for women became a lightning rod for US suffragists.

Nina Allender, “America First!/Russia First Universal Suffrage,” Suffragist, March 24, 1917. Courtesy of Belmont-Paul Women’s Equality National Monument, home of the historic National Woman’s Party, Washington, DC.

International Influences on the Modern Suffrage Movement
At the end of the nineteenth century, a more modern and militant suffrage internationalism emerged. A growing embrace of the term “feminism”—implying a movement that demanded women’s full autonomy—along with working women’s strong public presence, international socialism, and the Russian Revolution, contributed to the idea of a new womanhood breaking free from old constraints. [25]

International socialism had long upheld universal, direct, and equal suffrage as a demand, but in the 1890s, German socialist firebrand Clara Zetkin revived the goal, spearheading the inclusion of woman suffrage in the 1889 Second International in Paris. This gathering of socialist and labor parties from twenty countries in turn fostered vigorous women’s movements in Germany, France, and elsewhere in Europe. In Finland, socialist feminists and the Social Democratic Party were critical to the country’s, also Europe’s first, woman suffrage victory in 1906. [26]

Socialism, and the growing numbers of working women it inspired, breathed new life into the US suffrage movement. In 1909, women workers in New York demanded women’s right to vote, launching what became International Women’s Day. Over the next six years, working women exploded in labor militancy, viewing the vote as a tool against unjust working conditions and for what Polish-born labor organizer and suffragist Rose Schneiderman called “bread and roses.” The 1911 Triangle Shirtwaist Factory fire that claimed the lives of 145 workers, most of whom were young, immigrant women, made suffrage more urgent. [27] Collaborations with middle-class reformers helped spread many of the tactics that suffragists later employed on a wider scale: mass meetings, marches, and open-air street speaking. [28]

Immigrants and women from throughout the Americas were key to these efforts, and to connecting suffrage to broad social justice goals. In cigar factories in Tampa, Florida , the Puerto Rican anti-imperialist, anarchist, and feminist Luisa Capetillo inspired African American, Cuban American, and Italian American women workers with calls for woman suffrage, and for free love, workers’ rights, and vegetarianism. [29] From Texas , Mexican-born feminist Teresa Villarreal, who had fled the dictatorship of Porfirio Díaz, supported the Mexican Revolution, the Socialist Party, and woman suffrage, publishing with her sister Andrea that state’s first feminist newspaper, La Mujer Moderna (The Modern Woman) and starting the publication El Obrero (The Worker). [30] (Figure 3) In 1911, after the First Mexican Congress in Laredo, Texas, journalist Jovita Idar praised woman suffrage in La Crónica (The Chronicle) connecting it to her longstanding demands for Mexican American civil rights. [31]

Socialist, working-class suffrage militancy in England also galvanized the British Women’s Social and Political Union (WSPU), founded in 1903 by Emmeline Pankhurst. This group became the driving force in the British movement for nearly two decades, influencing militant suffrage activism around the world, including in China. [32] After the US suffragist Alice Paul , one of Pankhurst’s followers, was arrested in London in 1912, she helped organize the 1913 suffrage march in Washington, DC , and founded the Congressional Union for Woman Suffrage, later renamed the National Woman’s Party (NWP), that focused on a federal constitutional suffrage amendment. Its sash of purple, white, and yellow was modeled on the British purple, white, and green one, and its confrontational suffrage strategies of civil disobedience and picketing government buildings were inspired in large part by WSPU activism. [33]

The First World War, and a wave of suffrage legislation in Europe, further accelerated the US suffrage movement. [34] In the five years after 1914, suffrage passed in Denmark, Iceland, Russia, Canada, Austria, Germany, Poland, and England. Although the NWP had already been picketing the White House for several months, it was only when they embarrassed President Woodrow Wilson in front of a visiting Russian delegation, whose wartime cooperation he was trying to secure, that the first six suffragists were arrested. [35] These women, held on charges of obstructing traffic, were followed by a long line of US women imprisoned for suffrage activism. The violence they faced on the picket line (for holding signs saying “Kaiser Wilson” amid rabid anti-German sentiment) and in jail, with forced feedings during hunger strikes, became international news. [36] International pressure helped compel Wilson’s January 1918 announcement of support for suffrage, as he promoted the Unites States as a beacon of democracy. By this time, the House had already passed the suffrage amendment (the Senate would still vote against it), but Wilson’s endorsement was significant to US and international public opinion. In Uruguay, suffragists utilized Wilson’s support to push their legislators toward suffrage. [37] (Figure 4)

Two more years of federal and state lobbying and organizing led to ratification of the Nineteenth Amendment in August 1920. For Crystal Eastman, a pacifist, enthusiast of the Russian Revolution, and cofounder of the American Civil Liberties Union (ACLU), this accomplishment represented not an end, but a new beginning—one with internationalist significance: “Now [feminists] can say what they are really after,” she announced, “and what they are after, in common with all the rest of the struggling world, is freedom.” [38]

Figure 5. At this January 24, 1928, gathering of 200 women at the Asociación de Reporteros in Havana, Cuba, 5 US National Woman’s Party members joined Cuban suffragists to successfully plan to inject women’s rights into the 6th International Conference of American States meeting in Havana.

Courtesy of the Schlesinger Library, Radcliffe Institute, Harvard University, Cambridge, MA.

The International Afterlives of the US Suffrage Movement
Struggles for women’s voting rights did not end with ratification of the Nineteenth Amendment, which failed to eliminate the residency requirements, poll taxes, and literacy tests in the South that denied African American men and women the vote. African American women would not achieve this right until the 1965 Voting Rights Act. [39] For many, lack of rights in the United States drove new transnational activism. In the 1920s and ’30s, African American women collaborated with women from Africa, the Caribbean, and around the globe in the International Council of Women of the Darker Races (1922) and in Pan-Africanist and leftist organizing that connected demands for women’s political autonomy with those for antiracism, anticolonialism, Black nationalism, specifically viewing Black women’s self-determination as critical to broad and transformative social justice. [40]

US women’s involvement in Pan-American feminism was also an outgrowth of the US suffrage movement. In 1928, US and Cuban feminists created the Inter-American Commission of Women, the first intergovernmental organization in the world. Initially led by NWP suffrage veteran Doris Stevens, the commission forced an international treaty for women’s civil and political equal right into Pan-American and League of Nations congresses. A heterogeneous group of Latin American feminists, however, also recognized continuing efforts of US women to dominate the movement and developed their own anti-imperialist Pan-Hispanic feminism that demanded the vote. They asserted their own leadership over Pan-American feminism and used it to call for derechos humanos, which implied women’s political, civil, social, and economic rights alongside anti-imperialism and anti-fascism. At the 1945 San Francisco meeting that created the United Nations, Latin American female delegates, led by Brazilian feminist Bertha Lutz, drew on this movement to push women’s rights into the UN Charter and proposed what became the UN Commission on the Status of Women. In the wake of these events, numerous Latin American countries passed woman suffrage. [41] (Figure 5)

The transnational legacies of the suffrage movement are evident in US women’s ongoing quests for full citizenship today. Then as now, fights for women’s rights are connected to global movements for human rights—for immigrant, racial, labor, and feminist justice. [42] The internationalist history of the woman suffrage movement shows us that activists and movements outside the United States, and a broad range of diverse, international goals, were critical to organizing for that right deemed so quintessentially American—the right to vote. It reminds us how much we in the United States have to learn from feminist struggles around the world.

Bibliography and Further Reading

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V. The Trinity Test

Document 44: Letter from Commissar of State Security First Rank, V. Merkulov, to People’s Commissar for Internal Affairs L. P. Beria, 10 July 1945, Number 4305/m, Top Secret (translation by Anna Melyaskova)

Source: L.D. Riabev, ed., Atomnyi Proekt SSSR (Moscow: izd MFTI, 2002), Volume 1, Part 2, 335-336

This 10 July 1945 letter from NKVD director V. N. Merkulov to Beria is an example of Soviet efforts to collect inside information on the Manhattan Project, although not all the detail was accurate. Merkulov reported that the United States had scheduled the test of a nuclear device for that same day, although the actual test took place 6 days later. According to Merkulov, two fissile materials were being produced: element-49 (plutonium), and U-235 the test device was fueled by plutonium. The Soviet source reported that the weight of the device was 3 tons (which was in the ball park) and forecast an explosive yield of 5 kilotons. That figure was based on underestimates by Manhattan Project scientists: the actual yield of the test device was 20 kilotons.

As indicated by the L.D. Riabev’s notes, it is possible that Beria’s copy of this letter ended up in Stalin’s papers. That the original copy is missing from Beria’s papers suggests that he may have passed it on to Stalin before the latter left for the Potsdam conference.[41]

Document 45: Telegram War [Department] 33556, from Harrison to Secretary of War, July 17, 1945, Top Secret

Source: RG 77, MED Records, Top Secret Documents, File 5e (copy from microfilm)

An elated message from Harrison to Stimson reported the success of the Trinity Test of a plutonium implosion weapon. The light from the explosion could been seen “from here [Washington, D.C.] to “high hold” [Stimson’s estate on Long Island—250 miles away]” and it was so loud that Harrison could have heard the “screams” from Washington, D.C. to “my farm” [in Upperville, VA, 50 miles away][42]

Document 46: Memorandum from General L. R. Groves to Secretary of War, “The Test,” July 18, 1945, Top Secret, Excised Copy

Source: RG 77, MED Records, Top Secret Documents, File no. 4 (copy from microfilm)

General Groves prepared for Stimson, then at Potsdam, a detailed account of the Trinity test.[43]


Chapter 1

It was known that the Earth was round, so Columbus’s plan seemed plausible. The distance he would need to travel was not known, however, and he greatly underestimated the Earth’s circumference therefore, he would have no way of recognizing when he had arrived at his destination.

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    • Authors: P. Scott Corbett, Volker Janssen, John M. Lund, Todd Pfannestiel, Sylvie Waskiewicz, Paul Vickery
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    Highights in the History of Epilepsy: The Last 200 Years

    The purpose of this study was to present the evolution of views on epilepsy as a disease and symptom during the 19th and the 20th century. A thorough study of texts, medical books, and reports along with a review of the available literature in PubMed was undertaken. The 19th century is marked by the works of the French medical school and of John Hughlings Jackson who set the research on epilepsy on a solid scientific basis. During the 20th century, the invention of EEG, the advance in neurosurgery, the discovery of antiepileptic drugs, and the delineation of underlying pathophysiological mechanisms, were the most significant advances in the field of research in epilepsy. Among the most prestigious physicians connected with epilepsy one can pinpoint the work of Henry Gastaut, Wilder Penfield, and Herbert Jasper. The most recent advances in the field of epilepsy include the development of advanced imaging techniques, the development of microsurgery, and the research on the connection between genetic factors and epileptic seizures.

    1. Introduction

    The history of epilepsy is intermingled with the history of human existence the first reports on epilepsy can be traced back to the Assyrian texts, almost 2,000 B.C. [1]. Multiple references to epilepsy can be found in the ancient texts of all civilizations, most importantly in the ancient Greek medical texts of the Hippocratic collection. For example, Hippocrates in his book On Sacred Disease described the first neurosurgery procedure referring that craniotomy should be performed at the opposite side of the brain of the seizures, in order to spare patients from “phlegma” that caused the disease [2]. However, it was not until the 18th and 19th century, when medicine made important advances and research on epilepsy was emancipated from religious superstitions such as the fact that epilepsy was a divine punishment or possession [3, 4]. At the beginning of the 18th century, the view that epilepsy was an idiopathic disease deriving from brain and other inner organs prevailed. One should mention the important work in this field by William Culen (1710–1790) and Samuel A. Tissot whose work set the base of modern epileptology describing accurately various types of epilepsies.

    2. Anatomy and Physiology of Epilepsy

    2.1. Evolution of Thoughts around the Pathophysiology and Causes of Epilepsy

    At the beginning of the 19th century, physicians from the French medical school started to publish their research in the field of epileptology famous French physicians published their works on epilepsy such as Maisonneuve (1745–1826) [5], Calmeil (1798–1895) [6], and Jean-Etienne Dominique Esquirol (1772–1840). Maisonneuve stressed the importance for hospitalization of epileptic patients, categorized epilepsy into idiopathic and sympathetic and described the so-called sensitive aura of sympathetic epilepsy. Esquirol distinguished between petit and grand mal and along with his pupils Bouchet and Cazauvieilh studied systematically insanity and epilepsy conducting clinical and postmortem studies [3].

    During the second half of the 19th century, medicine focused on the delineation of pathophysiology of epilepsy and the topographic localization of epileptic seizures. Important works on epileptogenesis, aetiology, and taxonomy of epilepsy were published by prestigious physicians such as Théodore Herpin (1799–1865) in 1852 and 1867, Louis Jean François Delasiauve (1804–1893) in 1854, John Russell Reynolds (1828–1896) in 1861, and in 1881 by Sir William Richard Gowers (1845–1915). Regarding the delineation of the epileptic mechanisms, the proof that epilepsy derives from the brain came from the work of physiologist Fritsch (1838–1927) and psychiatrist Hitzig (1838–1907) in their paper entitled “On the Electric Excitability of the Cerebrum” they presented experiments in which they provoked seizures by electric stimulation in the brain cortex of dogs [7]. The work, however, of John Hughling Jackson (1835–1911) (Figure 1), set the scientific base of epileptology [3]. Jackson studied epilepsy on pathological and anatomical basis. His Study of Convulsions was the culmination of his research stressing the existence of localised lesions on cortex involved in epileptic convulsions. In 1873, Jackson gave the following definition for epilepsy: “Epilepsy is the name for occasional, sudden, excessive, rapid and local discharges of grey matter” [3].


    Epileptology, based on the work of Jackson and other eminent doctors of the 19th century, such as John Simon (1816–1904), John Russell Reynolds (1828–1896), Samuel Wilks, William Richard Gowers (1845–1915), Adolf Kussmaul (1822–1902), and Adolf Tenner, expanded and made important steps towards the elucidation of the pathophysiology of the disease and in the field of therapeutics [3].

    At the beginning of the 20th century, Santiago Ramón y Cajal (1852–1934), a Spanish pathologist, histologist, and neuroscientist, made important advances in the field of the microscopic structure of the brain and the nervous system. He was the first to describe the structure of neurons and synapses, a hallmark finding in the history of neurology. His findings were the culmination of efforts which began in 1887, when he started employing the Golgi staining in the study of the nervous system. As a reward of his efforts, Cajal, in 1906, received the Nobel Prize [8].

    In 1907, Gowers published his famous book The Borderlands of Epilepsy [9] focusing on faints, vagal and vasovagal attacks, migraine, vertigo, and some sleep symptoms, especially narcolepsy. In 1914, Dale (1875–1968) identified acetylcholine [10], the first neurotransmitter, a discovery confirmed later in 1921 by Loewi (1873–1961) who initially named it Vagusstoff, since it was released by the vagus nerve [11–13].

    During the 1920s, Lennox (1884–1960) and Cobb (1887–1968) focused on the effects of starvation, ketogenic diet, and altered cerebral oxygen in seizures and published their first monograph entitled “Epilepsy from the Standpoint of Physiology and Treatment” [14]. In 1922, Cobb and Lennox published another monograph entitled “Epilepsy and Related Disorders” (1928) [15] and an important paper summarizing their research entitled “The Relation of Certain Physicochemical Processes to Epileptiform Seizures” (1929) [16]. Lennox and Cobb focused on the effects of various stimuli to the generation of epileptic convulsions such as starvation, ketogenic diet, and lack of oxygen, most of them with negative results.

    During the 1940s, important discoveries were made in the field of psychomotor epilepsy. Klüver (1897–1979), a German-American psychologist, and Bucy (1904–1992), an American neuropathologist, well known for the discovery of the Klüver-Bucy syndrome, showed that changes in the behavior of monkeys could be associated with temporal lobe lesions [17]. In 1941, Jasper (1906–1999) and Kershmann proved that the temporal lobe is the site of origin of psychomotor seizures [18]. At the same period, Moruzzi (1910–1986) and Magoun (1907–1991) discovered the reticular formation in the brain [19]. Magoun continued his research with Lindsley (1907–2003) and Starzl (1926-) identifying various neural pathways within the brain and pointing out the important role in alert wakefulness as a background for sensory perception, higher intellectual activity, voluntary movements, and behaviors [20, 21]. Dawson in 1947 recorded the responses from the human scalp in response to somatosensory stimuli (somatosensory evoked potential) [22], whereas in 1949 Roberts (1920-) and Frankel discovered

    Important advances were made in the field of neuroscience and in the physiology of synapses by Eccles (1903–1997), Kandel (1929-), Spencer (1931–1977), Speckmann (1939-), Purpura, Meldrum, and others [24–38].

    James Kiffin Penry (1929–1996), in 1969, published important treatises such as the series Basic Mechanisms of the Epilepsies and afterwards Antiepileptic Drugs, Neurosurgical Management of the Epilepsies, Complex Partial Seizures, and their Treatment, and Antiepileptic Drugs Mechanisms of Action and Advances in Epileptology. In the same year Gastaut managed to organize a meeting in Marseilles attended by 120 members of ILAE and a preliminary classification of epilepsies was presented to a commission on terminology of epilepsy. The General Assembly of the ILAE accepted the first publication of clinical and electroencephalographic classification of epileptic seizures [39, 40].

    Dreifuss (1926–1997) worked on video-monitoring of absence seizures and helped in the classification of various epileptic conditions [41]. Prince et al. made the first studies of cellular phenomena of epileptic events in the human cortex [42–44]. Meldrum et al. proved that the assumption connecting brain damage from seizures as a result of hypoxia is wrong [45–47] he demonstrated that the excessive excitatory activity is responsible for the brain cellular loss.

    During the last two decades, various changes regarding the epileptic brain damage were also studied, such as the mossy fiber sprouting and synaptic reorganization [48–51].

    2.2. The Electrophysiology of Epilepsy and the EEG

    The first reference regarding the association of electric stimuli and brain activity came from the work of Fritsch (1838–1927) and Hitzig (1938–1907), who managed to cause convulsion to dogs by applying electric stimuli on the animals’ cortex. Five years later, in 1875, Caton (1842–1926) examined the electrical activity of nerve-muscle preparations and explored the possibility whether similar changes in electrical potential occurred in the brain [52]. A few years later, in 1890, Beck from Cracau in the pages of Zentrallblatt for Physiologie argued the case for the priority of the electrical activity of the brain, after electrical stimulation in the brain of dogs and rabbits [53]. In 1912, Kaufman (1877–1951), a Russian physiologist, noticed the electric changes in the brain during experimentally induced seizures, associating epileptic attacks with abnormal electric discharges [54] (EEG). In the same year, Pravdich-Neminsky (1879–1952), a Ukrainian physiologist, published the first animal EEG and the evoked potential of the mammalian (dog) [55].

    Two years later, Cybulski (1854–1919), a Polish physiologist and pioneer in electroencephalography, in cooperation with Jelenska-Macieszyna [56], published the first photographs of electroencephalography recording action potentials at a dog with focal epilepsy.

    Important discoveries in the fields of electroencephalography were made during the 1920s and 1930s. In 1929, Berger (1873–1941), a German neurologist, reported his findings on human brain waves [57], five years after his initial recording of the first human electroencephalogram. His results brought controversy and scepticism within the scientific community, but he was neither rejected nor ignored his results were confirmed later by Adrian (1899–1977) and Matthews [58]. In 1932, Berger reported sequential postictal EEG changes after a generalized tonicoclonic seizure, and in 1933 he published the first example of interictal changes and a minor epileptic seizure with 3/s rhythmic waves in the EEG [59, 60]. In the next few years until 1939, Berger made important observations on patients and on healthy subjects. His work on epileptic EEG was completed by Frederic Andrews Gibbs (1903–1992), an American neurologist, and Erna Leonhardt-Gibbs (1904–1987), technician and wife of Frederic, who, in collaboration with Lennox, established the correlation between EEG findings and epileptic convulsions [61–63] Lennox and Gibbs published in 1941 their monumental monograph “Atlas of Electroencephalography,” in which they included also mechanical and mathematical analysis of electroencephalograms [64].

    An important and influential figure in the field of EEG whose work was intensified during the 1950s was Henri Jean Pascal Gastaut (1915–1995) (Figure 2). After his graduation in 1945 from the University of Marseilles, Gastaut worked at the laboratory of William Grey Walter (1910–1977) in Bristol learning the basics of EEG and discovered photic stimulation as an EEG seizure activator. In 1949, he went to the Montreal Neurological Institute (MNI) with Wilder Penfield (1891–1976), famous Canadian neurosurgeon, and Herbert Jasper (Figure 3) (1906–1999), a Canadian psychologist, physiologist, anatomist, chemist, and neurologist who established in 1939 an EEG laboratory and studied the role of thalamic reticular structures in the genesis of metrazol-induced generalized paroxysmal EEG discharges and developed the concept of centrencephalic seizures [65]. After his return to Marseilles, Gastaut founded the International EEG Federation and, in 1953, became the Head of the Marseilles Hospital Neurobiological Laboratories establishing a school of neurology that dominated for the next decades. In 1958, he participated in the foundation of the Toul Ar C’hoat Center in Brittany for the education of epileptic children, whereas two years later he created the Saint Paul Center for epileptic children and, in 1961, the INSERM Neurobiology Research Unit. His contribution in the study of epileptology was monumental with his wife, Yvette, he defined five major human EEG patterns (lambda waves, pi rhythm, mu rhythm, rolandic spikes, and posterior theta rhythm) [66, 67]. He also described two syndromes under his name: Gastaut syndrome, a type of photosensitive epilepsy [68], and the Lennox-Gastaut syndrome (severe childhood encephalopathy) with onset in childhood with myoclonic seizures at night, head nodding, and drop attacks particularly prominent [69, 70]. He also studied photic and other self-induced seizures, startle epilepsy, HHE syndrome, and benign partial epilepsy of childhood with occipital spike-waves [68, 71–75].



    Wilder Penfield (1891–1976) on the right and Herbert Jasper (1906–1999) on the left (adopted by public domain at http://baillement.com/lettres/penfield.html).

    During the 1960s, important EEG studies were conducted in animals mainly by Prince and his research team demonstrating the spikes and waves associated with synchronous paroxysmal depolarizing bursts occurring in cortical neurons [76–79] and the spike-wave complex [80]. In 1968, Falconer recognized the importance of hippocampal sclerosis in temporal lobe epilepsy [81].

    2.3. The Patch-Clamp Technique

    An important development in the field of neuroscience was that of Neher (1944-), who invented the patch-clamp method to measure the flow of current through single-ion channels [82]. Neher and Sakmann developed the patch-clamp technique for which in 1992 they received the Nobel Prize [83]. Using the patch-clump technique, the various ion channels were able to be studied and, thus, the role of calcium channels was clarified in epilepsy [84].

    3. Therapy of Epilepsy

    3.1. The Evolution of Antiepileptic Surgery

    The first surgical procedures on epileptic patients were performed during the 19th century Heyman in 1831 was the first one to perform a surgery to an epileptic patient due to a brain abscess. Surgical excision was performed on November 25, 1884, by Dr. Godlee in the National Hospital of London. In 1880, Wilhelm Sommer (1852–1900), German neurologist and psychiatrist, described precisely Ammon’s horn lesions and epileptic manifestations part with sensible occurrence. Both Theodor Kocher (1841–1917), a Swiss surgeon from Bern, Nobelist, and pioneer in epileptic surgery, and Harvey Cushing (1869–1939), father of modern neurological surgery, in Baltimore dealt with posttraumatic epileptic disorders especially with patients displaying high endocranial pressure [85, 86]. In 1886, Horsley (1875–1916) excised an epileptogenic posttraumatic cortical scar at the National Hospital of London in a 23-year-old man under general anesthesia and discussed his choice of anesthesia: “I have not employed ether in operations on man, fearing that it would tend to cause cerebral excitement chloroform, of course, producing on the contrary, well-marked depression.” [87]. In Germany, Krause (1857–1937) and Foerster (1873–1941) refined Horsley’s technique [88, 89].

    At the beginning of the 20th century, Dandy (1886–1946) introduced hemispherectomy as a neurosurgical procedure in 1923 [90]. However it was not until the 1930s than important advances were made in epileptic surgery. The notion of operating the epileptogenic focus was introduced by Gibbs and Lennox in 1938 [91]. The introduction of EEG into epilepsy surgery was important in the development of surgical techniques.

    Penfield along with Jasper and Theodore Brown Rasmussen (1910–2002) in the Neurologic Center of University of Montreal also contributed importantly to the evolution of the surgery of epilepsy [92, 93]. Penfield applied the Foerster method for removing epileptogenic lesions on an epilepsy patient. After founding the Montreal Neurological Institute (MNI), in 1934, in collaboration with Jasper, he invented the Montreal procedure for the surgical treatment of epilepsy. According to the Montreal procedure, through the administration of local anesthetic, the surgeon removes part of the skull to expose brain tissue and, by the use of probes, the conscious patient describes to the surgeon his/her feelings so that the surgeon can identify the exact location of seizure activity. Then the surgeon proceeds in the removal of brain tissue in this location reducing the side effects of surgery [94]. Through his operations, Penfield was able to identify various brain centers and to create maps of the sensory and motor cortices of the brain. Research in MNI focused also on other areas of epileptology such as neurochemistry, oncology, and brain angiology. Penfield perfected and established his surgical procedures as a treatment of choice in intractable epilepsy, especially of neocortical regions [94–96]. In 1954, Penfield published with Jasper one of the greatest classics in neurology, Epilepsy and the Functional Anatomy of the Human Brain [93].

    Around the same period, van Wagenen and Herren (1897–1961), Chief of Neurosurgery at the University of Rochester Medical Center (URMC), performed and perfected the procedure of callosotomy [97]. Bailey (1892–1973), an American neuropathologist, neurosurgeon, and psychiatrist, known for his work on brain oncology, was the first to attempt temporal lobectomies for psychomotor seizures and the first to use electrocorticography for intraoperative localization [98]. One should also mention the method of hemispherectomy introduced by McKenzie (1892–1964) [99] and Krynauw in 1950 [100].

    Bailey and Gibbs in 1951 employed the EEG as a guide to perform temporal lobe surgery [98], whereas, in 1953, Falconer, a neurosurgeon from New Zealand, in London, introduced the en bloc anterior temporal lobe resection and the term mesial temporal sclerosis [101]. The work of Margerison and Corsellis led to the term of hippocampal sclerosis [102], a pathological entity which was initially described almost 80 years earlier by Sommer in 1880 [103]. Niemeyer, in 1958, suggested a more selective procedure of resection of the mesiobasal limbic structure [104], a technique which was later on abandoned.

    The next important step in the field of antiepileptic surgery was done by Tailarach and his team. In 1957, Tailarach (1911–2007) published his stereotactic atlas, a work that changed the future of epilepsy neurosurgery the next decade [105] Marcel David adopting Tailarach’s views supported the creation of an operating room in which stereotactic surgery would take place. Within this operating room teleradiography would take place and the use of parallel X-ray beams would avoid distortions of skull, vessels, ventricles, and the frame and grids used for guiding the placement of intracranial electrodes. The first stereotactic surgery operating room was opened in Sainte-Anne in 1959 [106]. Tailarach’s team obtained two members, Alain Bonis and Gabor Szikla. In 1962, the term stereoelectroencephalography (SEEG) was introduced by Talairach and Jean Bancaud (1921–1993). Their method brought a revolution in the surgery of epilepsy, since it allowed investigative presurgical and therapeutic surgical phases to be completely dissociated. Tailarach and Bancaud employing their technique showed that lesional and irritative zones had a variable topographic relationship within the epileptogenic zone [14]. Tailarach’s method allowed the individualization of epileptic surgery for each patient [18, 19].

    During the 1960s, Bogen and Vogel reintroduced the procedure of callosotomy [107] as a procedure for certain cases of pharmacoresistant epilepsy with severe atonic akinetic seizures. In 1961, White published a comprehensive review on the surgical procedure of hemispherectomy summarizing the results of 269 published cases [108] in the treatment of infantile-type hemiplegia and seizures. In 1969, Morell and Hanbrey introduced “multiple subpial transection” (MST) for nonresectable epileptic foci [108].

    At the beginning of the 1980s, in the field of antiepileptic surgery, MTLE suggested selective amygdalohippocampectomy (AHE) with the trans-Sylvian approach, replacing the anterior temporal lobe resection [109]. The advent of modern diagnostic techniques such as MRI, PET, and SPECT (single photon emission tomography), 31 P and 1 H-MR spectroscopy, and MEG (magnetoencephalography) revolutionized epileptic surgery, as well. The application of microsurgery led to selective operations with less complications such procedures include “selective amygdalohippocampectomy” [109], the innovation of older ones, anterior callosotomy, subtotal functional hemispherectomy, and extended multilobar resections, and the introduction of new operative techniques such as multiple subpial transection [109] and gamma knife.

    3.2. Drug Therapy

    As far as therapies and the neurophysiology of epilepsy are concerned, much were already known during the second half of 19th century. Treatment of epilepsy till that time mostly consisted of herbal and chemical substances. In 1857, Sir Locock (1799–1875) discovered the anticonvulsant and sedative traits of potassium bromide and began treating his patients. From that point, potassium bromide became a choice treatment for humans with epileptic seizures and nervous disorders until the 1912 discovery of phenobarbital [110].

    In 1912, Hauptmann (1881–1948), a German physician, introduced phenobarbital in the therapy of epilepsy, one of the first antiepileptic drugs [111]. Phenobarbital was brought to market by the drug company Bayer using the brand Luminal. Hauptmann administered Luminal to his epilepsy patients as a tranquilizer and discovered that their epileptic attacks were susceptible to the drug. The introduction of animal models in the study of the anticonvulsant properties of various substances will contribute to the development of new antiepileptic drugs.

    The next drug introduced in the therapy of epilepsy was phenytoin in 1938. Although phenytoin was already known from 1908 and was synthesized by Heinrich Biltz (1865–1943), there was no interest for that drug since it did not have any sedative properties. Merritt (1902–1979), an eminent academic neurologist, along with Putnam (1894–1975), discovered, in 1938, the anticonvulsant properties of phenytoin (Dilantin) and its effect on the control of epileptic seizures publishing their results in a series of papers [112–115]. Phenytoin became the first-line medication for the prevention of partial and tonic-clonic seizures and for acute cases of epilepsies or status epilepticus, giving an alternative therapeutic choice for patients not responding to bromides or barbiturates. In 1946, a new antiepileptic drug was added in the quiver of antiepileptic therapy, trimethadione it was reported by Richards and Everett to prevent pentylenetetrazol-induced seizures and to be effective especially in absence seizures [116].

    During the 1950s, new drugs came up such as carbamazepine in 1953 [117], primidone in 1954, ethosuximide in 1958 by Vossen [118], sodium valproate in 1963 by Meunier et al. [119], and sultiame. Buchtal and Svensmark were the first ones in 1960 to measure the levels of the antiepileptic drugs in the blood [120]. Although carbamazepine and valproate were available in Europe during the 1960s, no other drug was licensed in the USA. The development of carbamazepine was based on the neuroleptic drug chlorpromazine from Firma Rhône-Poulenc in Lyon. Jean Pierre (1907–1987) and Pierre Deniker (1917–1998), French psychiatrists, used chlorpromazine in Centre Hospitalier Sainte Anne in Paris to treat patients with schizophrenia. However, research on neuroleptic drugs continued in Geigy labs carbamazepine was synthesized by Schindler and Blattner (1921-?) at J. R. Geigy AG, Basel, Switzerland, 1953, in the course of development of another antidepressant drug imipramine [117]. Initial animal screening showed that carbamazepine was effective against trigeminal neuralgia, which was confirmed by clinical trials [121]. Antiepileptic effects were reported in 1963 and 1964 [122, 123]. It was used as an anticonvulsant drug in the UK since 1965 and has been approved in the USA since 1974. The reason for the delay of approval in the USA was due to reports of aplastic anemia caused by the drug [124]. Ethosuximide was first introduced in clinical practice in the early 1950s for the therapy of absence “petit mal.”

    In 1967, valproate came up as a new promising antiepileptic drug. Valproate was initially synthesized in 1881 by Beverly Burton in the USA and was initially employed as an organic solvent [125] his research on valproate begun in Würzburg, Germany. The anticonvulsant properties of valproate were reported by Pierre Eymard, who worked at Firma Berthier laboratories in Grenoble, and it was first released as antiepileptic drug in France in 1967 [126] after the publication of preclinical studies by Garraz et al. in 1964. During 1970, it received license to other European countries, but in the USA it was not licensed before 1978.

    In 1970, Penry and Cereghino were employed in designing clinical trials for antiepileptic drugs (AEDs). Harvey Kupferberg joined their team and together they developed a methodology for measuring the blood-levels of albutoin, an experimental drug which was proved to be ineffective in epilepsy. The first edition of Antiepileptic Drugs came forth as a result of their research efforts in 1972 [127]. Carbamazepine was the first drug to be licensed by the FDA based on the results of clinical trials. Pippenger (1939-) developed methods for measuring blood-levels of AEDs [128]. Other antiepileptic drugs introduced during the 1970s were clobazam (1,5-benzodiazepine) (1970), clonazepam (1,4-benzodiazepine) (1970), and piracetam.

    The last decade newer antiepileptic drugs such as vigabatrin (1989), lamotrigine (1990), oxcarbazepine (1990), gabapentin (1993), felbamate (1993), topiramate (1995), tiagabine (1998), zonisamide (1989 in Japan and 2000 in the USA), levetiracetam (2000), stiripentol (2002), pregabalin (2004), rufinamide (2004), lacosamide (2008), eslicarbazepine (2009), and perampanel (2012) were used. FDA ended clinical use of felbamate in 1994 due to its association with complications. The newer generation antiepileptic drugs including vigabatrin, felbamate, gabapentin, lamotrigine, tiagabine, topiramate, levetiracetam, oxcarbazepine, zonisamide, pregabalin, rufinamide, and lacosamide have improved tolerability and safety compared to their older counterparts. Stiripentol, pregabalin, rufinamide, lacosamide, eslicarbazepine, and perampanel are licensed for adjunctive use only. The research in antiepileptic drugs is an active field and many drugs are currently under development in clinical trials including eslicarbazepine acetate, brivaracetam, and retigabine.

    In phase III clinical trials (which used eslicarbazepine doses of 400, 800, and 1200 mg/day), eslicarbazepine was well tolerated, with the most common AEs reported to include dizziness, headache, and somnolence [129–132]. Two large-scale, phase III clinical trials have been conducted for retigabine. In both studies, AEs leading to discontinuation included dizziness, somnolence, headache, and fatigue [133–136].

    3.3. The Idea of Ketogenic Diet

    Ketogenic diet was used for the first time in the treatment of epilepsy in 1911 by the French physicians Guelpa and Marie. It was introduced as a diet full of fats and low in proteins and carbohydrates and managed to treat 20 children and adults with epilepsy reporting decrease in the number of seizures [137]. However, fasting and other diets were employed for the treatment of epilepsy since the Hippocratic era [138].

    In 1922, Hugh Conklin, an osteopathic physician from Michigan, applied this diet to epileptic patients with encouraging results. Conklin believed that epilepsy was due to toxins that damage the brain and so he obliged his patients to a strict diet. In his papers, he wrote, “I restrict from my patients any kind of food except of water for as long as their physical condition allows it.” Conklin had a personal interest in ketogenic diet, since by this way he tried to cure his nephew, who suffered from drug-resistant epilepsy. Several papers have been published about the usefulness of ketogenic diet and the indications that will lead to the beginning of such a treatment [139, 140]. Further studies were published by Talbot [141], Helmholz [142], Lennox [143], and Bridge and Iob [144]. Charles Howland, a wealth New York lawyer, funded his brother John Howland to search whether there was a scientific basis for the success of the starvation treatment by which his epileptic son was treated [145, 146]. Dr. John Howland, Professor of paediatrics, John Hopkins Hospital, used this funding to create the first laboratory at the Harriet Lane Home for Invalid Children. John Howland Memorial Fund was established at John Hopkins Hospital and supported the research on the ketogenic diet [147]. Although multiple investigations have been performed, the anticonvulsive mechanisms of ketogenic diet remain unexplained. In the years to follow, many authors published articles with positive or negative results. Then, this therapy was forgotten for many years, since progress in pharmaceutical therapy was in the foreground. In the last 20–30 years, KD experienced a revival, especially in the Anglo-American world where it is established as a treatment option for therapy-resistant infantile epilepsy. Livingston [148], Hopkins and Lynch [149, 150], and Huttenlocher [151] were the advocates of this direction. The multitude of side effects and procedural problems however reduced the initial euphoria. Only as recently as 1996, the Institute Charlie (the institute was named by a father of a child with epilepsy which was treated with KD) educated the public about the benefit of KD, organized seminars and training courses, and published a book entitled The Epilepsy Diet Treatment: An Introduction to the Ketogenic Diet. More recently new versions of ketogenic diet such as the modified Atkins diet have been employed successfully for the treatment of children and adults with refractory epilepsy [152, 153] and are especially recommended in cases of pharmacologically intractable epilepsy.

    3.4. The Technique of Vagus Nerve Stimulation

    An important advance in epilepsy treatment was the development of the technique of vagus nerve stimulation (VNS), especially for patients experiencing serious adverse effects of antiepileptic drugs. VNS involves implantation of a programmable signal generator (neurocybernetic prosthesis NCP) in the chest cavity, and the stimulating electrodes carry electrical signals from the generator to the left vagus nerve [154].

    3.5. Complimentary Treatments for Epilepsy

    During the last two decades a series of alternative or complimentary therapies have emerged in the therapy of epilepsy. These include relaxation therapies such as massage, aromatherapy, reflexology and chiropractic therapy, holistic therapies such as herbal medicine (St. John’s Wort, evening primrose oil), homeopathy, Ayurvedic medicine, and traditional Chinese medicine (herbal remedies plus acupuncture), traditional and psychological therapies such as autogenic training, neurofeedback, and other psychological therapies, and music therapy. Although some of those therapies seem to have an effect, most of them are considered as complementary therapies and more studies are needed in order to establish their therapeutic effect and their usefulness in everyday clinical practice [155]. Recent studies have pinpointed the use of cannabidiol and medical marijuana for the treatment of epilepsy [156].

    4. The Evolution of Thoughts around Epilepsy: Society and Science Cooperate for the Good of Epileptic Patients

    Just before the turn of the twentieth century, in 1898, William Pryor Letchworth (1823–1910), a businessman devoted to charities, and Frederick Peterson (1859–1938), an eminent American neurologist and Professor of neurology, Columbia University, organized the first National Association for the Study of Epilepsy and the Care and Treatment of Epileptics in the USA and the Craig Colony in Sonyea, the first comprehensive public epilepsy center, along with other eminent physicians such as Roswell Park (1852–1914), Professor of surgery, University of Buffalo Medical School, and a surgeon, Buffalo General Hospital, William P. Spratling (1863–1915), American neurologist, known for his studies in epilepsy, and Frederick Munson [157, 158]. William Spartling introduced for the first time the term “epileptologist” for a physician specializing in epilepsy.

    During World War I, Pearce Bailey organised the systematic examination of military recruits creating a database with epidemiological data on epilepsy. The same year is considered to be the founding year of the American Epilepsy Society (AES) in commemoration of a joint meeting focusing on epilepsy organised by the Association for the Research in Nervous and Mental Disease (ARNMD) and the American League Against Epilepsy (ALAE). The proceedings of this meeting recapitulated the state of the art on epilepsy research and stimulated further research [159]. The first president of AES was Dr. Charles Dair Aring (1904–1998), a renowned American neurologist and pioneer in medical education in the USA.

    The beginning of the 1950s was marked by the establishment by the US congress and the American Academy of Neurology of the National Institute of Neurological Diseases and Blindness (NINDB), now known as the National Institute of Neurological Disorders and Stroke. The main purpose of this institute was to study and treat the neurological and psychiatric casualties of World War II under the direction of Bailey. Bailey recruited in his team Maitland Baldwin (1918–1970), a famous American neurosurgeon, as the Chief of surgical neurology, Bethesda, Donald Bayley Tower (1919–2007), in 1953, as the Chief of the section on clinical neurochemistry, and Cosimo Ajmone-Marsan (1918–2004), as the Head of the electroencephalography branch in 1954. As a result of their cooperation, a treatise on temporal lobe epilepsy was published [160].

    During the 1960s, in 1961, the International Bureau for Epilepsy (IBE) was established as an organisation of laypersons and professionals interested in the medical and nonmedical aspects of epilepsy (http://www.ibe-epilepsy.org). In 1962, the US Public Health Service Surgeon General created the Neurological and Sensory Disease Control Program (NSDCP) supporting research on epilepsy in various ways. In 1965, Anthony Joseph Celebrezze (1941–2003), Secretary of the Department of Health, Education, and Welfare, organized a meeting for the expansion of epilepsy research and services. As a result of it, in 1966, Surgeon General William Stewart (1921–2008) created the Surgeon General’s Public Health Service Advisory Committee on the Epilepsies, whereas, in 1969, the Society for Neuroscience was established. Stewart created two subcommittees: one with David Daily entitled Service Training Subcommittee with Terrance Capistrant and James Cereghino as Executive Secretaries and a second one with Arthur Ward entitled Research Training Subcommittee with William Caveness and J. Kiffin Penry as Executive Secretaries [65].

    In 1970, a classification of epilepsies was proposed by the International League Against Epilepsy [161]. This classification was revised several times through the last decades, in order to clarify terms and meanings and to avoid any confusion towards the understanding of epilepsy. In 1975, the US Commission for the Control of Epilepsy and its Consequences was established under the direction of Dr. Richard H. Masland and Dr. David Daly, creating a plan for nation-wide action on epilepsy.

    During the last two decades, epileptics are being evaluated psychologically and socially and, before 1990, quality of life tools were developed. In 1981, the International League Against Epilepsy (ILAE) published the first classification of epilepsies which were discussed extensively and revised in 1989 [162–164] the classification and terminology for epileptic seizures and syndromes provided a fundamental instrument for diagnosing, organizing, and differentiating the epilepsies.

    During the 1990s, the decade of the brain, WHO in collaboration with ILAE and IBE launched the Global Campaign Against Epilepsy in 1997, in order to bring epilepsy out of the shadows and to further improve diagnosis, treatment, prevention and social acceptability. In 1993, the ILAE defined fever seizures as the seizures occurring in childhood after the age of 1 month, usually between 3 months and 6 years old, associated with a febrile illness, not caused by an infection of central nervous system (CNS), without previous neonatal or unprovoked seizure, and not meeting criteria for other acute symptomatic seizures [165]. In 2001, the ILAE Task Force on Classification and Terminology under Engel proposed a diagnostic scheme for people with epileptic seizures and with epilepsy [166] which was also supported in 2006 by the ILAE Classification Core Group [167]. ILAE’s classification of epilepsies and convulsive disorders was extensively discussed and new classification was suggested but not implemented since 2010 when ILAE published a new classification [168, 169].

    5. The Contribution of Imaging Techniques in the Diagnosis of Epilepsy

    After the end of World War I, Dandy (1886–1946), an American neurosurgeon, described in 1918 and 1919, pneumoventriculography and pneumoencephalography [170–172], the first imaging techniques of the brain with the use of X-rays. For his discovery, he was nominated by Hans Christian Jacobaeus for the Nobel Prize in 1933. In the field of imaging, it was not until 1972 when computerized tomography (CT) was invented by the British engineer Godfrey Hounsfield (1919–2004), EMI Laboratories, UK, and by the South African physicist Allan MacLeod Cormack (1924–1998), Tufts University, Massachusetts [173]. The use of 18 F-fluorodeoxyglucose for determination of local cerebral localization began in 1977 [174, 175].

    During the last decades great steps have been taken to the diagnostic approach of epilepsy by the use of neuroimaging. Techniques as magnetic resonance tomography (MRI), SPECT, and PET contributed to the diagnosis of pathological areas of the brain, such as tumors, cortical/subcortical dysgeneses, inflammation, strokes, vascular dysplasia, and posttraumatic insult. Newer imaging techniques in the diagnosis of epilepsy include functional MRI [176] (fMRI), clinical proton MR spectroscopy [177], and magnetoencephalography (MEG) [178].

    6. Genetics in Epilepsy

    The first connection between heredity and epilepsy was made in 1903 by Lundborg (1868–1943), a Swedish physician, notorious for his views on eugenics and racial hygiene, who published his research on the genetics of progressive myoclonic epilepsy first described by Heinrich Unverricht in 1891 (1853–1912) [179] his analysis was pioneering since he was able to trace back the disease in the family since the 18th century. In that way, Lundborg was also a pioneer in the study of human genetics.

    The concept of eugenics became an issue in the control of epilepsy during the 1930s in 1936, the American Neurological Association Committee for the Investigation of Eugenical Sterilization published a report [180] stating that sterilization of epileptics should be voluntary and conducted under supervision and only with patient consent.

    The most important evolution, however, in the field of the genetics of epilepsy, took place during the last twenty years in 1989, Leppert was the first to identify the link between chromosome 20 and idiopathic human epilepsy syndrome in a family with benign familial neonatal convulsions [181]. Epilepsy still remains a field of active research, occupying different medical specialties. The growing evidence on the connection between various genes and epilepsies is the cutting edge of modern epilepsy research, and in the next decades new exciting discoveries are going to change epileptology [182]. Recently, in 2011, Engel published the identification of reliable biomarkers which would greatly facilitate differential diagnosis, eliminate the current trial-and-error approach to pharmacotherapy, facilitate presurgical evaluation, and greatly improve the cost-effectiveness of drug discovery and clinical trials of agents designed to treat, prevent, and cure epilepsy [167].

    7. Conclusions

    The fascinating history of epilepsy is connected with the history of humanity early reports on epilepsy go back to the ancient Assyrian and Babylonian texts, scanning a period of almost 4,000 years. The first hallmark in the history of epilepsy is the Hippocratic texts which set in doubt the divine origin of the disease. Major advances in the understanding of epilepsy came much later, during the 18th and 19th century theories on epilepsy during this period are formulated on a solid scientific basis and epileptics are for the first time treated as patients and not as lunatics or possessed. During this period, experimental studies were conducted and advances made in the pathology of the disease and the connection of epilepsy with various psychiatric symptoms. The work of John Hughlings Jackson was preceded by a plethora of studies by Dutch, German, English, and French physicians who evolved scientific thought and performed thorough studies on epilepsy. The advent of the 20th century led to the in-depth understanding of the mechanisms of the disease, the development of effective drugs, and neuroimaging methods. Last but not least, one should mention the important advances in the molecular biology of the disease and the connection of various genes with various forms of epilepsy.

    Conflict of Interests

    The authors declare that there is no conflict of interests regarding the publication of this paper.

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    Copyright © 2014 Emmanouil Magiorkinis et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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