Frederic Lewy: how the two World Wars changed his life, work, and name.

In 1912, Friedrich Lewy described the inclusion bodies present in Parkinson disease and in Lewy body dementia. Throughout his life, Lewy fought in two wars - on opposite sides. He was born in Berlin in a Jewish family, and served in the German Army in World War I. In the following years, on many occasions he had to change his line of research due to Nazi persecution. Lewy became a naturalized American, changed his name to Frederic Henry Lewey, and served in the US Army as a lieutenant colonel. Lewy died in 1950 and never used the famous eponym in his papers.

Em 1912, Friedrich Lewy descreveu os corpos de inclusão presentes na doença de Parkinson e na demência com corpos de Lewy. Ao longo sua vida, Lewy lutou em duas guerras, em lados opostos. Ele nasceu em Berlin em uma família de origem judaica e serviu no Exército alemão na Primeira Guerra Mundial. Nos anos seguintes, passou muitas vezes teve de mudar sua linha de pesquisa devido à perseguição Nazista. Lewy naturalizou-se americano, mudou seu nome para Frederic Henry Lewey, e serviu no Exército americano como tenente-coronel. Lewy morreu em 1950 e nunca usou o famoso epônimo em seus artigos.

William Rutherford Sanders (1828-1881) and his neurologically fertile years (1865-1868).

William Rutherford Sanders (1828-1881) was an Edinburgh physician who occupied the Chair of Pathology at the University of Edinburgh from 1869 to 1881. All of his published output between 1865 and 1868 was concerned with neurology. In arguing that a patient did not have paralysis agitans, Sanders (1865) employed the term "Parkinson's disease" for the first time in the English-language literature to distinguish between the disorder that Parkinson (1817) termed "paralysis agitans" and other types of shaking palsies. He contributed a major chapter on the same topic to Russell Reynolds's A System of Medicine (1868). Sanders also investigated the innervation of the palate and facial muscles (1865), and in 1866 recorded the autopsy findings in two cases of aphasia. Here, for the first time in the English-language literature, he described findings that supported Broca's location of the representation of speech to a particular area of the left cerebral hemisphere.

Camillo Negro and his contributions to neurology.

An historical review of the contributions made by Italian professor, Camillo Negro, to neurology. Negro published several books on clinical neurology, was one of the pioneers of scientific films and described numerous neurological diseases. He is best known for describing the cogwheel phenomenon in patients with Parkinson's disease but also described a sign of peripheral facial paralysis.

Camillo Negro and his contributions to neurology / Camillo Negro e suas contribuições à Neurologia

ABSTRACT An historical review of the contributions made by Italian professor, Camillo Negro, to neurology. Negro published several books on clinical neurology, was one of the pioneers of scientific films and described numerous neurological diseases. He is best known for describing the cogwheel phenomenon in patients with Parkinson's disease but also described a sign of peripheral facial paralysis.

RESUMO Os autores apresentam uma revisão histórica sobre as contribuições do Professor italiano Camilo Negro para à neurologia. Negro publicou vários livros sobre clínica neurológica e também foi um dos pioneiros na realização de filmes científicos, com a descrição de inúmeras doenças neurológicas. Ele é mais conhecido pela descrição do fenômeno da roda denteada em pacientes com a doença de Parkinson, mas também descreveu um sinal da paralisia facial periférica.

[From "Shaking Palsy" to "Parkinson's Disease": Was Charcot Correct?]

In light of contemporary knowledge, we review a classic case of "Parkinson's disease" presented by Charcot. The patient, Bachère, provided an opportunity to change the name of the disease from "Shaking palsy" to "Parkinson's disease". We also explore a total of 4 cases of "Parkinson's disease in extension", especially that of Rab. Léon, described in 2 articles (1889 and 1892) in Nouvelle Iconographie de la Salpêtrière. Although diagnosed by Charcot as a type of Parkinson's disease, and historically accepted as such, he may have been misled. English text is available

Centenary of Tretiakoff's thesis on the morphology of Parkinson's disease, evolved on the grounds of encephalitis lethargica pathology.

In his Thèse de Paris (1919) Konstantin Tretiakoff (1892-1956) described the two main morphological lesions in Parkinson's disease: the loss of pigmented nerve cells in the Substantia nigra and the intracellular inclusion bodies in idiopathic paralysis agitans, calling them "Corps de Lewy," which already had been described by F. H. Lewy in 1912. Tretiakoff's findings on idiopathic Parkinson's disease were confirmed years later by Rolf Hassler in his dissertation on anatomy and pathology of Substantia nigra in Berlin (1938, 1939). German authors in the 1920s underestimated the significance of both findings (Bielschowsky, 1922; Lewy 1923/1924; Spatz 1927), especially Lewy himself. Lewy (1923) and other German neurologists and neuropathologists like Felix Stern (1922, 1928), Goldstein (1922), and Spatz (1927; Luksch & Spatz, 1923) acknowledged the typical Nigra-lesions only for postencephalitic Parkinsonism. It is argued that Tretiakoff's selective attention for the Substantia nigra was guided by the frequency of epidemic encephalitis lethargica and its preponderance of nigral pathology. This impression can be derived from Tretiakoff's early paper on that disease (Marie & Tretiakoff, 1918) and from Paul Foley's opus magnum (2018). Two outstanding neurologists dedicated to this issue are called into memory: Gabrielle Lévy, the successor of Tretiakoff in the Salpêtrière laboratory, and Felix Stern, who died in 1942 as a victim of Nazi terror. The eponym Lewy-bodies went back to Lafora and Tretiakoff ("Corps de Lewy"). Newly expressed doubts about Lewy's primacy or Lafora's credit for the eponym (Lafora-bodies since 1911) can be refuted with the studies of Greenfield and Bosanquet (1953) and Greenfield (1963) by illustrating their different staining properties.

Cell-based therapy for Parkinson's disease: A journey through decades toward the light side of the Force.

This review describes the history, development, and evolution of cell-based replacement therapy for Parkinson's disease (PD), from the first pioneering trials with fetal ventral midbrain progenitors to future trials using stem cells as well as reprogrammed cells. In the spirit of Tom Isaacs, the review takes parallels to the storyline of Star Wars, including the temptations from the dark side and the continuous fight for the light side of the Force. It is subdivided into headings based on the original movies, spanning from A New Hope to the Last Jedi.

Parkinson's disease: a short story of 200 years.

After Alzheimer's disease, Parkinson's disease (PD) is the second most prevalent and incidental neurodegenerative disorder, affecting more than 2% of the population older than 65 years old. Since it was first described 200 years ago by Dr James Parkinson, great steps have been made in the understanding of the pathology. However, the cause(s) that initiates and perpetuates the neurodegenerative process is (are) still not clear. Thus, early diagnosis is not available, nor are there efficient therapies that can stop neurodegeneration. PD clinical features are defined by motor (like bradykinesia, resting tremor, gait impairment) and non-motor symptoms (like constipation, apathy, fathigue, olfactory dysfunction, depression and cognitive decline) that get more severe as the disease advances. Neuropathological hallmarks comprise selective loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc) and Lewy bodies (LB) in different nuclei of the nervous system. Numerous studies have shown that these pathological features are aggravated by the confluence of other contributing factors, such as a genetic component, exposure to environmental toxins, mitochondrial dysfunction, increase of oxidative stress, calcium imbalance and chronic neuroinflammation, among others. Here, we provide a summary of the actual state of PD's pathology, the most studied molecular mechanisms, classic and novel therapeutic strategies and diagnosis methods, especially highlighting recent advances in these 200 years.

[Breve recorrido histórico de la enfermedad de Parkinson a 200 años de su descripción].

The original description of what currently is known as Parkinson's disease was published 200 years ago. During both these centuries, knowledge on symptomatology, pathophysiology, genetics and pharmaceutical and surgical treatment has significantly increased; however, this nosological entity continues to be of imprecise origin and progressive evolution. In the present review, the historical events that contributed to describe and improve the understanding of this disease are summarized.

La descripción original de lo que ahora conocemos como enfermedad de Parkinson fue publicada hace 200 años. Durante estos dos siglos, el conocimiento sobre la sintomatología, fisiopatología, genética, tratamiento farmacológico y quirúrgico se ha incrementado notablemente; no obstante, esta entidad nosológica continúa siendo de origen impreciso y de curso progresivo. En la presente revisión se resumen los acontecimientos históricos que contribuyeron a describir y mejorar el entendimiento de esta enfermedad.

What influences placebo and nocebo responses in Parkinson's disease?

Placebo treatment is associated with clinical improvements in many medical conditions, but is particularly important in Parkinson's disease because improvements are common, marked, and associated with objective neurochemical and neurophysiologic changes. This review will focus on the effect of the placebo in patients with PD and will discuss the pathophysiology, observed characteristics of motor and nonmotor placebo responses, and the patient and study characteristics that modify the placebo response. Similar to the placebo response, nocebo and lessebo effects alter clinical trial outcomes and impact conclusions. Whereas placebo-associated improvements are positively viewed by patients in clinical practice, they complicate clinical trials. The authors suggest strategies to reduce placebo effects during randomized placebo-controlled trials evaluating new therapies. © 2018 International Parkinson and Movement Disorder Society.

ANNIVERSARY REVIEW: 50 years since the discovery of bromocriptine.

Ergotism is the long-term ergot poisoning by ingestion of rye or other grains infected with the fungus Claviceps purpurea and more recently by excessive intake of ergot drugs. It has either neuropsychiatric or vascular manifestations. In the Middle Ages, the gangrenous poisoning was known as St. Anthony's fire, after the order of the Monks of St. Anthony who were particularly skilled at treating the condition. In 1917, Prof. Arthur Stoll returned home to Switzerland from Germany, to lead the development of a new pharmaceutical department at Sandoz Chemical Company. Stoll, using the special methods of extraction learned from his work with his mentor Willstetter, started his industrial research work with ergot. He succeeded in isolating, from the ergot of rye, ergotamine as an active principle of an old popular remedy for excessive post-partum bleeding. The success of this discovery occurred in 1918 and was translated into a pharmaceutical product in 1921 under the trade name Gynergen. In subsequent work, Stoll and his team were leaders in identifying the structure of the many other alkaloids and amines produced by Claviceps purpurea This was the cultural background and scientific foundation on which bromocriptine was discovered.

Jean-Martin Charcot and Parkinson's disease: Teaching and teaching materials.

James Parkinson's 1817 seminal article was not well known in France until 1861, when Jean-Martin Charcot and his friend, Alfred Vulpian, published a detailed description in French of paralysis agitans. Their article provided clinical information to help French physicians make an accurate diagnosis by considering gait, shaking and rigidity as well as masked facies. As Charcot always had a strong desire to teach, this article describes his lessons on Parkinson's disease from 1868 to 1888, and also examines the teaching approach he used to pass on his latest findings to his students and colleagues. Charcot also used his role as thesis advisor to disseminate Parkinson's work, and seven of the theses he oversaw, which until now have been overlooked, reveal another facet of his teacher-student relationship. These dissertations provided Charcot with an opportunity to highlight what he had already identified concerning what is today referred to as 'Parkinson-plus syndromes'. Finally, this report concludes with an historical survey of the teaching materials that Paul Richer and Albert Londe developed for the Master at La Salpêtrière to provide him with visual documentation.

200 Years of Parkinson's disease: what have we learnt from James Parkinson?

2017 marks 200 years since James Parkinson's published his 'Essay on the Shaking Palsy'. Although now most famous for describing the condition that came to bear his name, Parkinson had a wide range of interests and his influence spread beyond medicine. In this review, we provide a biography of James Parkinson's remarkable life.Parkinson's paper not only comprehensively described the symptoms of Parkinson's disease (PD), but challenged his peers to better understand the pathophysiology of the PD. Key observation over the next 2 centuries, included the recognition of the link between the substantia nigra and PD and the discoveries of dopamine deficiency in patients with PD. We review the subsequent development of pharmacological and surgical therapies. Despite great progress over the last 200 years, Parkinson's hopes for a 'cure if employed early enough' or that 'some remedial process may ere long be discovered by which at least the progression of the disease may be stopped' remain apposite today and we reflect on the challenges ahead for the next century.

A Tribute to James Parkinson.

Exactly 200 years ago, the London surgeon-apothecary James Parkinson (1755-1824) published a 66-page-long booklet entitled An Essay on the Shaking Palsy, which contains the first clear clinical description of the shaking palsy or paralysis agitans, which we now refer to as Parkinson's disease. However, the value of this essay was not fully recognized during Parkinson's lifetime, which spanned the American Revolution, the French Revolution, and the Napoleonic Wars. James Parkinson was one of the most singular figures of his time and place. He was successively or concomitantly a virulent political activist, a popular medical writer, a scholarly medical contributor, a highly appreciated parish doctor, a prominent amateur chemist, a devoted madhouse doctor, and a renowned paleontologist. It is that branch of geology that brought Parkinson fame during his lifetime. He was an insatiable collector of fossils, minerals, and shells that came to form the core of the museum that he set out at his home in Shoreditch, England. These specimens are beautifully illustrated in his Organic Remains of a Former World (1804-1811), a three-volume treatise that rapidly became a standard paleontology textbook. Parkinson was a founding member of the Geological Society of London, and in recognition of his contribution to the nascent field of paleontology his name was given to many fossils, particularly ammonites (e.g. Nautilus parkinsoni). Hence, we owe much to Mr. Parkinson, the Paleontologist, as he used to be referred to after his death, for such a vast and multifaceted contribution to natural science and medicine.

The 200-year journey of Parkinson disease: Reflecting on the past and looking towards the future.

It took almost 100 years before a meaningful advance occurred in any basic science understanding of Parkinson disease (PD) following James Parkinson's description in 1817. The Lewy body was described in 1912, and the substantia nigra was found to be depigmented with neuronal loss and gliosis in 1919. The link between dopamine and PD began in 1957, 140 years after Parkinson's Essay. Arvid Carlsson and Oleh Hornykiewicz were the major pioneers. The revolutionary therapeutic breakthrough was the introduction of high dosage levodopa therapy by George Cotzias in 1967. Following 40 years of the dopa/dopamine era, we have entered the era of alpha-synuclein, the protein present in Lewy bodies. Heiko Braak found that alpha-synuclein accumulates initially in the olfactory system and lower brainstem and then travels in an anatomic pattern to involve other regions of the brain and thereby cause progressive symptoms. Alpha-synuclein was somehow converted to a rogue protein. Where this originates and how it is propagated are under intense investigation. At the same time that the alpha-synuclein era was developing, clinical advances took place by recognizing PD as hosting a wide variety of nonmotor features with eventual cognitive impairment in many. Therapeutics has also evolved. Although the most effective therapy for the motor features remains levodopa, surgical approaches and drugs for nonmotor problems continue to expand our ability to treat people with PD. We can expect therapeutic advances in neuroprotection as the basic science discoveries uncovered in the alpha-synuclein era are translated into effective treatments.

Parkinson's disease - the story of an eponym.

One of the most prevalent neurodegenerative diseases worldwide is still referred to as 'Parkinson's disease'. The condition is named after James Parkinson who, in 1817, described the shaking palsy (paralysis agitans). In the bicentennial year of this publication, we trace when and why the shaking palsy became Parkinson's disease. The term was coined by William Rutherford Sanders of Edinburgh in 1865 and later entered general usage through the influence of Jean-Martin Charcot and the school that he nurtured at the Salpêtrière Hospital in Paris. Despite a move towards more mechanism-based nosology for many medical conditions in recent years, the Parkinson's disease eponym remains in place, celebrating the life and work of this doctor, palaeontologist and political activist.