German Neurologist Research Articles

Impact of drug diversity on treatment effectiveness in relapsing-remitting multiple sclerosis (RRMS) in Germany between 2010 and 2018: real-world data from the German NeuroTransData multiple sclerosis registry

ObjectiveTo evaluate the impact of drug diversity on treatment effectiveness in relapsing-remitting multiple sclerosis (RRMS) in Germany.DesignThis study employs real-world data captured in-time during clinical visits in 67 German neurology...

Adolph Seeligmüller (1837-1912) and the first graphic illustration of the "toe phenomenon" (later called "Babiński sign") in the medical literature.

The "toe phenomenon" refers to the extension (dorsiflexion) of the great toe, which occurs instead of the normal flexion following stimulation of the foot sole. Its clinical significance was not fully appreciated until Joseph Jules François Félix Babiński (1857-1932) described it in 1896. In 1881, Ernst Strümpell (1853-1925) had described a continuous (tonic) extension of the big toe, a finding that years later the French neurologist Jean-Athanase Sicard (1872-1929) recognized as an equivalent of the "toe phenomenon", also indicating pyramidal tract dysfunction. Previously, this phenomenon had been mentioned in patients only passingly and without providing a picture of it. In 1887, the German neurologist Adolph Seeligmüller (1837-1912) mentioned the tonic extension of the big toe among the characteristic clinical features of spastic infantile hemiplegia-a condition first described by the Austrian physician Moritz Benedikt (1835-1920) in 1868. Seeligmüller incorrectly attributed the tonic extension of the big toe to spastic contracture of the extensor hallucis longus muscle. However, he put great emphasis on this sign and considered it worth being illustrated. Adolph Seeligmüller therefore provided the very first graphic illustration of the (tonic) "toe phenomenon" in the medical literature. Of note, the first photographic illustration of this sign made by Babiński appeared only in 1900, when it had already been adopted by neurologists all over the world.

Evaluation of evidence grades in psychiatry and psychotherapy guidelines

BackgroundInformation regarding the distribution of evidence grades in psychiatry and psychotherapy guidelines is lacking. Based on the German evidence- and consensus- based (S3) psychiatry and psychotherapy and the Scottish Intercollegiate Guidelines Network (SIGN) treatment guidelines, we aimed to specify how guideline recommendations are composed and to what extent recommendations are evidence-based.MethodsData was collected from all published evidence- and consensus-based S3-classified psychiatry and psychotherapy guidelines. As control conditions, data from German neurology S3-classified guidelines as well as data from recent SIGN guidelines of mental health were extracted. Two investigators reviewed the selected guidelines independently, extracted and analysed the numbers and levels of recommendations.ResultsOn average, 45.1% of all recommendations are not based on strong scientific evidence in German guidelines of psychiatry and psychotherapy. A related pattern can be confirmed for SIGN guidelines, where the mean average of recommendations with lacking evidence is 33.9%. By contrast, in the German guidelines of neurology the average of such recommendations is 16.5%. A total of 24.5% of all recommendations in the guidelines of psychiatry and psychotherapy are classified as level A recommendations, compared to 31.6% in the field of neurology and 31.1% in the SIGN guidelines. Related patterns were observed for B and 0 level recommendations.ConclusionGuidelines should be practical tools to simplify the decision-making process based on scientific evidence. Up to 45% of all recommendations in the investigated guidelines of psychiatry and psychotherapy are not based on strong scientific evidence. The reasons for this high number remain unclear. Possibly, only a limited number of studies answer clinically relevant questions. Our findings thereby question whether guidelines should include non-evidence-based recommendations to be methodologically stringent and whether specific processes to develop expert-opinion statements must be implemented.

Freud and Albert Moll: how kindred spirits became bitter foes.

This article explores the antagonism between Sigmund Freud and the German neurologist and sexologist Albert Moll. When Moll, in 1908, published a book about the sexuality of children, Freud, without any grounds, accused him of plagiarism. In fact, Moll had reason to suspect Freud of plagiarism since there are many parallels between Freud's Drei Abhandlungen zur Sexualtheorie and Moll's Untersuchungen über die Libido sexualis. Freud had read this book carefully, but hardly paid tribute to Moll's innovative thinking about sexuality. A comparison between the two works casts doubt on Freud's claim that his work was a revolutionary breakthrough. Freud's course of action raises questions about his integrity. The article also critically addresses earlier evaluations of the clash.

Experience of Practice-Based Psychiatrists and Neurologists During the COVID-19 Pandemic

To date, to our knowledge there are no studies regarding attitudes and experiences of outpatient medical personnel during a pandemic. This study's aim was to evaluate the impact of the COVID-19 pandemic in March 2020 on German psychiatrists and neurologists. An e-mail and fax-based short survey of 2,072 practice-based psychiatrists and neurologists was performed including Likert-type questions on personal burden and concerns, anticipated risk of infection, practice management as well as anxiety and sleep problems. 396 physicians returned the questionnaire (19 %). More than 60 % of the participants felt restricted strongly or very strongly, more than 30 % were strongly and very strongly concerned. They anticipated a high own risk of infection. However, 91 % did not report any contact with patients positively screened for COVID-19, which they were aware of. One third felt financially threatened and loss of business volume was anticipated. 18 % reported, that the pandemic triggers substantial anxiety. Sleep problems, which occur at least almost every night, were rarely reported (9 %). Practice-based psychiatrists and neurologists are negatively affected by the COVID-19 pandemic.

Do doctors treat themselves differently than their patients? Study on the self-treatment of migraine among German neurologists and pain specialists.

To investigate whether the self-treatment of migraine among neurologists and pain specialists corresponds to national medical guidelines and treatment of patients. An email cross-sectional survey was sent to members of the German Society for Neurology, German Pain Society and German Migraine and Headache Society containing questions on demographics, professional experience and specialization and - in case participants suffered from migraine - questions about their migraine and its treatment. 175/418 (41.9%) participants suffered from migraine (m: 29.3%; f: 55.2%, 45.9 ± 10.7 years). For acute migraine attacks, 96.6 % of them use a first-line treatment according to the medical guidelines. Seventeen (9.7%) are currently taking a migraine prophylaxis, 52.9% of these use a recommended first-line prophylaxis. In all, 21.7% are not taking a prophylactic treatment despite an indication (based on number of monthly migraine days) for it, due to fear of side-effects, low intensity of migraine attacks and a sufficient effect of acute medication. This group of participants was younger, less experienced and specialized and was mainly employed (vs. self-employed) compared to those taking a prophylaxis. A total of 96.6% reported treating their patients in line with current guidelines; 14.3% would treat themselves differently when they were their own patients. The self-treatment of acute migraine attacks for the most part complies with the guidelines but, regarding the indication for a prophylaxis, a more divergent treatment approach was observed among younger, less experienced physicians. For the majority of physicians there is no difference between self-treatment and treatment of migraine patients.

Men without a past? (Honorary) Presidents of the German Neurological Society and their NS past

This paper aims at reconstructing the biographies of six German neurologists during and after the "Third Reich". Between 1957 and 1976, five of them were presidents of the German Neurological Society (DGN), the sixth was appointed honorary president in 1981. They all joined the National Socialist German Workers' Party (NSDAP) or Storm Troopers (SA) as young doctors between the ages 20 and35 years. According to the current state of research they thus have to be classified as formally incriminated, yet none of them developed significant (health) political activities, with the slight exception of Eberhard Bay (1908-1989), who once acted as expert witness in an Hereditary Health Court trial. Gustav Döhring (1909-1963), NSDAP member since 1937, Pette student and co-founder of the DGN, was secretary of the Society for many years and editor of acommemorative publication. Johannes Hirschmann (1910-1991), also aparty comrade since 1937, served as an army and military hospital doctor from 1939 to 1945. Richard Jung (1911-1986) had joined the SA in 1934. This entailed his immediate dismissal after the war from the University of Freiburg but benefitting from the support by the dean he could pursue his career not long thereafter. RobertCharles Behrend (1919-1996) became aparty member at the age of 20 years and with his time in office in 1975-1976 he was the last of the post-war presidents of the DGN connected to National Socialism in Germany. Older than these five was honorary chairman Gustav Bodechtel (1899-1983) a member of the SA, NSDAP and other Nazi organizations. He was dismissed in 1946 but reinstated just 1 week later due to the interventions by the Medical Academy Düsseldorf and the Mayor of the City. New findings on these personalities are exclusively based on archival research. This underlines the necessity of resorting to sources previously neglected when investigating biographies of twentieth century neurologists.

Max Nonne (1861-1959) and his attitude towards "euthanasia"

Max Nonne, an internationally renowned German neurologist, acted from 1918 to 1924 as president of the (first) Society of German Neurologists (GDN). Appointed honorary president in 1925, he held this position in the (second) German Neurological Society (DGN) until his death. Since 1961, this association has honored 16neurologists with acommemorative medal named after Nonne. His outstanding findings in various fields of neurology are uncontested and some of them live on as eponyms (Nonne-Apelt syndrome, Nonne-Froin syndrome, Nonne-Milroy-Meige syndrome); however, recent archival studies and an analysis of individual publications deeply darkened the image of the "grey eminence" of German neurology. Records kept at the Hamburg State Archive prove that in amemorandum from 1941/1942 following the example of Binding and Hoche, Nonne firmly approved the killing of "life absolutely unworthy of living". In areport addressed to the District Court of Hamburg he attested in 1946 that many physicians charged with manslaughter acted in accordance with the regulations governing "child euthanasia", resulting in the withdrawal of the accusation. In afurther statement from 1949 he confirmed that the killing of children and the "euthanasia program" during the NS era were consistent with the state of medical science. An earlier book chapter authored by Nonne immediately after World WarI suggested that his social-Darwinistically colored concept of mankind was developed clearly before the Nazi era. Notwithstanding the arrangement to which he came with the new powers after 1933 and his acceptance of tributes to him by them, he repeatedly stood up for his Jewish colleagues. He was never aNazi, nevertheless, he engaged in activities that fostered NS "euthanasia" going far beyond a"mentality of approval".

Heinrich Pette (1887-1964) and the difficult assessment of his role from the Weimar Republic to the Federal Republic of Germany

For along time, biographical sketches and obituaries have focused on Pette's instantly recognizable scientific contributions to German neurology and neurovirology; however, they often ignored or marginalized his role as vice-president of the Society of German Neurologists and Psychiatrists (GDNP) during the Nazi era. Recent investigations and reports based on newly discovered records question such one-sided assessments and paint acontradictory picture. Pette joined the National Socialist German Workers' Party (NSDAP) and the NS Medical Association in 1933 and in the same year signed the "vow of allegiance of the professors to Adolf Hitler and the National Socialistic State". In 1934 he succeeded Nonne as professor for neurology in Hamburg and from 1935 headed the neurological branch of the NS-controlled Society of German Neurologists and Psychiatrists (GDNP). As aresult, Pette had astrong influence on all activities of this organization and had contact with party leadership and the government. In principle, he was not opposed to the "Law for the Prevention of Genetically Diseased Offspring" and produced various expert reports addressed to the Appellate Hereditary Health Court in Hamburg. Simultaneously, he advocated differentiated diagnostics and rejected hasty sterilizations. He seems to have been acquainted with the "euthanasia" program and concomitant research projects but was not involved in them. During and after alengthy denazification trial he stylized himself into a nonpolitical scientist representing an "oppositional attitude". In 1950 he was co-founder of the German Neurological Society (DGN) and was president until 1952 and then honorary president. Since 1969 the DGN awards the Heinrich Pette Prize. The Foundation for Research in Spinal Poliomyelitis founded by him shortly after WWII was named after him after his death. Since 2011 it bears the name "Heinrich Pette Institute, Leibniz Institute for Experimental Virology". In future, aprudent dealing with this ambivalent legacy seems to be advisable.

Georg Schaltenbrand (1897-1979) and his research without moral boundaries on multiple sclerosis

In 1953 the prominent German neurologist Georg(es) Schaltenbrand became president of the German Neurological Society (DGN) and in 1967 honorary president. Less well known is the fact that from 1933 to 1936 he was member of the "Stahlhelm" and the Storm Troopers (SA). In 1937 he joined the National Socialist German Workers' Party (NSDAP) and other Nazi organizations. For the last three decades Schaltenbrand's name has primarily been associated with human experiments performed in 1940. His objective was to prove the viral etiology of multiple sclerosis (MS). To that end he injected cerebrospinal fluid (CSF) drawn from allegedly infected monkeys and MS patients into severely handicapped patients from the psychiatric asylum Werneck near Schweinfurt as well as into severely ill patients from the University Hospital of Würzburg without their consent. Weeks later he withdrew CSF samples from the recipients, sometimes repeatedly to control parameters of inflammation. Although not all details of his test series can be clarified, there is no doubt that he violated prevailing laws and ethical standards. According to the present state of knowledge, he was the only German professor of neurology during the Nazi era who performed such experiments on humans in terms of "research without moral boundaries". He later justified his actions by arguing that he had intended to exert apositive effect on the mentally ill. Judicial investigations ended in 1948 without an indictment. Long after his death, in 1994 the "Schaltenbrand experiments" became known to awider public and three years later the Medical Faculty of Würzburg condemned the unethical research and distanced itself from its former member. Today, Schaltenbrand's study is assessed as an unacceptable form of research on particularly vulnerable patients for the benefit of third parties. As aresult, ethical norms formulated in the 1930s were reinforced by international guidelines, e.g. the Declaration of Helsinki drafted by the World Medical Association.

Otfrid Foerster (1873-1941) and his ambivalent attitude towards National Socialism

When Adolf Hitler was appointed Chancellor of the Reich Otfrid Foerster was almost 60years old and an internationally renowned neurologist, neurosurgeon and apioneer of localization research. Since 1922 he held the chair of neurology in Breslau (Wroclaw) and from 1925 to 1932 he was president (later honorary president) of the first Society of German Neurologists. In 1934 "his" Neurological Research Institute in Breslau was inaugurated. Biographical studies have unanimously established that he has never been amember of the party, that he found himself promptly marginalized after 1933 within his own ranks, and that he never participated in eugenic measures or "euthanasia" activities. Are-reading and analysis of his relevant papers and publications on neurology reveal however reverences paid to the Nazi state, which are surprising in this clarity. A possible explanation for Foerster's overall ambivalent attitude, he was married to anon-Aryan woman (in Nazi jargon), is the threat posed to his relatives by Nazi racial hygiene laws. On the other hand, there are clear indications of his conservative German national patriotism encouraging and supporting arestrengthened state and the National Socialist vision of the German Reich as a"great power". Further investigations will have to show how the numerous influential factors that had abearing on his biographical characteristics, political attitude, medical research interests and private motivation should be weighted.

Oswald Bumke (1877-1950)-silence as resistance?

In 1924 Oswald Bumke was appointed as Emil Kraepelins successor to the Chair of Psychiatry at the University of Munich. After 1933 he was apromoting member of the SS and the National Socialist Teachers Federation but he was never amember of the National Socialist German Workers' Party (NSDAP). In 1933 he assumed the presidency of the Society of German Neurologists but only 2 years later he withdrew from the executive board because of scientific and personal differences with Ernst Rüdin, the new "strong man" of the merged Society of German Neurologists and Psychiatrists. After the end of WWII, Bumke affirmed that despite his exposed position as professor of psychiatry during the NS era, he had lacked any influence and that he had sabotaged the "Law for the Prevention of Genetically Diseased Offspring" (GzVeN). He declared that for scientific reasons he had been extremely critical of the GzVeN and even had expressed his views in various publications. Nevertheless, he supported forced sterilization in his treatise "The State and Mental Diseases" published in 1939. His statement that the clinic in Munich had manipulated diagnoses in order to protect patients from eugenic measures and "euthanasia" refers to apotential interference, but as documents are lacking this cannot be substantiated. After 1940 Bumke functioned as aconsulting military psychiatrist in expert reports. Political assessments from this period presented him as politically reliable. His biography exemplarily shows that ameticulous juxtaposition of post-war documents with correspondent records stemming from the Nazi period is imperative in order to arrive at a source-critical well-founded and differentiated evaluation.

Neurologists and neuroscientists during the "Third Reich": attempt at an assessment

On behalf of the German Neurological Society (DGN) former presidents, honorary presidents and honorary members were checked for possible formal or ideological affiliations with National Socialism (NS) 75 years after the NS dictatorship. When the DGN was reformed in 1950, 6 of the7 "founding fathers" were former members of the National Socialist German Workers' Party (NSDAP), which is in strong contrast with the traditional narrative of a"new beginning". The first four (Pette, Schaltenbrand, Vogel and Döring) and in total 10 out of13 incumbent presidents until 1976 (Zülch, Bay, Hirschmann, Jung, Bauer, Behrend) as well as honorary president Bodechtel had belonged to the NSDAP, Storm Troopers (SA), or "Schutzsstaffel" (SS). Approximately two thirds of the German and Austrian honorary members appointed until 1985 had been associated with the NS system or the NS ideology (e.g. Becker, Birkmayer, Jacob, Reichardt, Seitelberger, Tönnis and von Weizsäcker). The individual attitude of neuroscientists towards eugenics ranged from approval to refusal and a few had been involved with (Appellate) Hereditary Health Courts. None of the physicians considered here were directly involved in killing patients but several of them knew of the "concomitant research" in the context of "euthanasia". Others used research resources generated during the "euthanasia"-programme and after 1945. The only professor of neurology who conducted ethically inacceptable human experiments was Georg Schaltenbrand. Almost all neurologists could pursue their career after the war, sometimes after having undergone lengthy denazification trials but very few of them were willing to face up to their past. Categorizations, such as "collaborators", "beneficiaries" and "physicians with ambivalent roles" should be replaced by amore differentiated assessment. When dealing with the past of German neurology it would be advisable to resort to acategorization of remembrance instead of naming awards after incriminated persons.

Growing Academic Physiatry: The Comparative Impact of Baruch Grants to Harvard Medical School and Columbia College of Physicians and Surgeons. Part I

Growing Academic Physiatry: The Comparative Impact of Baruch Grants to Harvard Medical School and Columbia College of Physicians and Surgeons. Part I

A novel longitudinal framework aimed at improving the teaching of the neurologic examination.

To develop an educational framework basis for improving the teaching of the neurologic examination (NE) by asking German neurologists to (1) identify the basic elements of the screening NE and (2) nominate the steps they would deem mandatory for medical students to master. We conducted a questionnaire-based survey among neurologists working in a hospital or ambulatory setting in southwest Germany. To define the screening NE, neurologists were asked to list the NE components they normally use in clinical encounters with patients in whom neurologic findings are unlikely. Furthermore, they were asked to identify additional elements of the NE which they would consider mandatory for students to master. Our neurologists nominated a set of 23 elements as being essential for a screening NE. There was high consensus among the 2 groups, and the results were concordant with international data. Furthermore, nearly 60 additional maneuvers of the NE were deemed obligatory for students to master. Our results reinforce the international consensus for screening NE components and confirm a large set of additional examination steps that medical students should master, thereby indicating the need for an educational NE teaching concept. To solve this educational challenge, we propose a longitudinal curriculum that incorporates the "core + clusters" framework, thus combining the screening NE (core) with hypothesis-driven sets of maneuvers (clusters). Based on our data, we provide an initial proposal for the core and neurologic diagnostic clusters which is applicable to both novice and advanced learners across the continuum of training.

Immunomodulatory therapy in 6427 relapsing-remitting multiple sclerosis (RRMS) patients over time under special consideration of switching to oral DMD: A retrospective data analysis

NeuroTransData, a german neurology network of 66 physicians, has been collecting real world data in a specific MS database with more than 23.000 patients for 10 years. Longitudinal assessment of MS patients on injectable DMD who switched to oral DMD and other DMDs. RRMS-patients stable on injectable DMDs (Avonex®, Rebif®, Betaferon/Extavia® Copaxone®) for 4,3y (median) were analyzed for 6,1y (median) regarding clinical course and potential switch to oral and other treatments. 2682 (41.7%) of these 6427 patients were switched to oral DMD. The other patients stayed on their DMD for 4,6 years (median). The main reasons for switching were insufficient therapeutic effect (34,2%), side effects (18,1%) and patient’s wish (18,2%). After 1.1 years (median), 716 (26,7%) of these already switched patients were switched once again to another DMD, 123 (17,2%) switched back to their first DMD. 1735 patients (65%) remained on their first switch therapy. Observation period was 3,8 years (median). The main reason for switching from injectable to oral DMD was the therapeutic effect, followed by patient’s wish and side effects. In those patients who switched a second time, side effects were the main reason for switching. Most patients (65%) who switched from injectible to oral DMDs remained on that therapy during the observation period.

History of cerebral localization and the emigration plight of three neuroscience giants from Nazi Germany: Josef Gerstmann, Adolf Wallenberg, and Franz Josef Kallmann.

The Nazi regime held power for well over a decade in Germany and were steadfast in their anti-Semitic agenda. Among the massive cohort of immigrants to America were approximately 5056 Jewish physicians, including several highly esteemed neurologists and neuroscientists of the time. Emigrating to a new world proved difficult and provided new challenges by way of language barriers, roadblocks in medical careers, and problems integrating into an alien system of medical training and clinical practice. In this article, the authors examine the tumultuous and accomplished lives of three Jewish German and Austrian neurologists and neuroscientists during the time of the Third Reich who shaped the foundations of neuroanatomy and neuropsychology: Josef Gerstmann, Adolf Wallenberg, and Franz Josef Kallmann. The authors first examine the successful careers of these individuals in Germany and Austria prior to the Third Reich, followed by their journeys to and lives in the United States, to demonstrate the challenges an émigré physician faces for career opportunities and a chance at a new life. This account culminates in a description of these scientists' eponymous syndromes.Although their stories are a testimony to the struggles in Nazi Germany, there are intriguing and notable differences in their ages, ideologies, and religious beliefs, which highlight a spectrum of unique circumstances that impacted their success in the United States. Furthermore, in this account the authors bring to light the original syndromic descriptions: Gerstmann discovered contralateral agraphia and acalculia, right-left confusion, and finger agnosia in patients with dominant angular gyrus damage; Wallenberg described a constellation of symptoms in a patient with stenosis of the posterior inferior cerebellar artery; and Kallmann identified an association between hypogonadotropic hypogonadism and anosmia based on family studies. The article also highlights the unresolved confusions and international controversies about these syndromic descriptions. Still, these unique cerebral syndromes continue to fascinate neurologists and neurosurgeons across the world, from residents in training to practicing clinicians and neuroscientists alike.

Discussing sexuality with Parkinson\u2019s disease patients: a multinational survey among neurologists

Sexual dysfunction is a major non-motor feature of Parkinson’s disease (PD) that may affect the quality of life of many patients. In a Dutch survey, we demonstrated that neurologists often fail to discuss sexuality with their patients. Our objective was to determine to which extent neurologists in Spain and Germany address sexuality with their patients and whether cross-cultural differences exist. A 30-item questionnaire was sent out to 1650 German and 460 Spanish neurologists. The questionnaire addressed attitudes, knowledge, barriers, and feelings of responsibility regarding sexuality in PD. 160 German and 32 Spanish respondents completed and returned the questionnaire. The majority of German and Spanish participants discuss sexual dysfunction ‘regularly’ with male patients (61.7% and 78.9%, respectively), but ‘seldom’ with female patients (68.8% and 78.1%, respectively). Important barriers for German and Spanish respondents to discuss sexual dysfunction were patients not expressing sexual complaints spontaneously (52.9% and 75.0%, respectively) and insufficient consultation time (32.2% and 71.9%, respectively). Sexual dysfunction in PD was considered important by 68.3% of German and 96.9% of Spanish participants. German and Spanish neurologists do not routinely discuss sexual dysfunction with their patients, although many of them consider it important to address this topic. It is unclear why this lack of discussing sexual dysfunction is especially found for female patients and whether cultural aspects are involved. We recommend a self-assessment tool for patients to track their symptoms prior to consultation visits and advocate local guidelines that formulate who is responsible for discussing sexual dysfunction.

Safety and efficacy of epigallocatechin gallate in multiple system atrophy (PROMESA): a randomised, double-blind, placebo-controlled trial

Multiple system atrophy is a rare neurodegenerative disease characterised by aggregation of α-synuclein in oligodendrocytes and neurons. The polyphenol epigallocatechin gallate inhibits α-synuclein aggregation and reduces associated toxicity. We aimed to establish if epigallocatechin gallate could safely slow disease progression in patients with multiple system atrophy. We did a randomised, double-blind, parallel group, placebo-controlled clinical trial at 12 specialist centres in Germany. Eligible participants were older than 30 years; met consensus criteria for possible or probable multiple system atrophy and could ambulate independently (ie, were at Hoehn and Yahr stages 1-3); and were on stable anti-Parkinson's, anti-dysautonomia, anti-dementia, and anti-depressant regimens (if necessary) for at least 1 month. Participants were randomly assigned (1:1) to epigallocatechin gallate or placebo (mannitol) via a web-generated permuted blockwise randomisation list (block size=2) that was stratified by disease subtype (parkinsonism-predominant disease vs cerebellar-ataxia-predominant disease). All participants and study personnel were masked to treatment assignment. Participants were given one hard gelatin capsule (containing either 400 mg epigallocatechin gallate or mannitol) orally once daily for 4 weeks, then one capsule twice daily for 4 weeks, and then one capsule three times daily for 40 weeks. After 48 weeks, all patients underwent a 4-week wash-out period. The primary endpoint was change in motor examination score of the Unified Multiple System Atrophy Rating Scale (UMSARS) from baseline to 52 weeks. Efficacy analyses were done in all people who received at least one dose of study medication. Safety was analysed in all people who received at least one dose of the study medication to which they had been randomly assigned. This trial is registered with ClinicalTrials.gov (NCT02008721) and EudraCT (2012-000928-18), and is completed. Between April 23, 2014, and Sept 3, 2015, 127 participants were screened and 92 were randomly assigned-47 to epigallocatechin gallate and 45 to placebo. Of these, 67 completed treatment and 64 completed the study (altough one of these patients had a major protocol violation). There was no evidence of a difference in the mean change from baseline to week 52 in motor examination scores on UMSARS between the epigallocatechin gallate (5·66 [SE 1·01]) and placebo (6·60 [0·99]) groups (mean difference -0·94 [SE 1·41; 95% CI -3·71 to 1·83]; p=0·51). Four patients in the epigallocatechin gallate group and two in the placebo group died. Two patients in the epigallocatechin gallate group had to stop treatment because of hepatotoxicity. 48 weeks of epigallocatechin gallate treatment did not modify disease progression in patients with multiple system atrophy. Epigallocatechin gallate was overall well tolerated but was associated with hepatotoxic effects in some patients, and thus doses of more than 1200 mg should not be used. ParkinsonFonds Deutschland, German Parkinson Society, German Neurology Foundation, Lüneburg Foundation, Bischof Dr Karl Golser Foundation, and Dr Arthur Arnstein Foundation.

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

ABSTRACTIn 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.