[How studies on curare contributed to the development of neurophysiological research in Brazil]. / Importance des études transnationales sur le curare dans le développement de la recherche en neurophysiologie au Brésil.

Curare is a poison obtained from different species of plants in South America, which was used in arrows by the natives. Its lethal paralyzing potential and mechanism of action began to be explored in the 19th century. In this article, we highlight the research on this poison and the fruitful exchanges between the Brazilian Emperor Dom Pedro II and the researchers João Baptista de Lacerda, Louis Couty and Alfred Vulpian who contributed to the development of experimental neurophysiology in Brazil. Vulpian found that curare does not affect the nerve itself, but acts between the nerves and the muscle, through a "ligand substance" - this Vulpian's pioneering concept is often wrongly attributed to Claude Bernard. These prestigious scientists contributed to the transnational circulation of knowledge that later yielded in the preparation of curare purified extract used for convulsive therapy and anesthesia.

Title: Importance des études transnationales sur le curare dans le développement de la recherche en neurophysiologie au Brésil. Abstract: Le curare, un poison obtenu à partir de différentes espèces de plantes en Amérique du Sud, était utilisé sur les flèches par les autochtones. Son potentiel paralysant mortel et son mécanisme d'action ont commencé à être explorés par les chercheurs au XIXe siècle. Dans cet article, nous rappelons l'historique des recherches sur ce poison et les échanges entre l'empereur brésilien Dom Pedro II et les chercheurs João Baptista de Lacerda, Louis Couty et Alfred Vulpian qui ont beaucoup contribué au développement scientifique brésilien. Vulpian a découvert que le curare n'affecte pas le nerf lui-même, mais agit entre celui-ci et le muscle, par l'intermédiaire d'une « substance de liaison ¼ ­ ce concept développé par Vulpian est souvent attribué à tort à Claude Bernard. Les travaux pionniers de ces savants prestigieux ont ultérieurement abouti à la préparation d'extrait purifié de curare, d'intérêt thérapeutique majeur pour le traitement de convulsions et pour l'anesthésie.

Historical Features Regarding the Neuropathic Outbreaks in Brazilian Troops in the Paraguayan War.

During the Paraguayan War, Brazilian army and navy officers attributed outbreaks of combatant limb weakness with particular features such as tingling to palustrian causes. A dietary basis was not fully suspected at the time, and the popular name beriberi had not been coined. During wartime, there was a shortage in the food supply in addition to poor environmental conditions and diarrheal diseases, and many reports of "palustrian cachexia" were made. There are also reports of the use of native flora to feed troops, as well as alcoholism. There are also accounts of the death of horses with symptoms similar to those of combatants. It was reported that black soldiers were more resistant to "palustrian cachexia." This article presents the disease ecology and clinical manifestations of beriberi at wartime, linked to starvation and consumption of pickled food and native flora. These military explorations and operations in the Paraguayan War happened more than 150 y ago and present some aspects of wilderness medicine in the past.

Louis Pasteur and Dom Pedro II engaged in rabies vaccine development.

Louis Pasteur is the renowned chemist and microbiologist of the 19th century involved in the development of the rabies vaccine. He worked with a researchers team in the laboratory, mainly Pierre Paul Emile Roux, and also physicians in the clinical practice approach and the defense of Pasteur's anti-rabies technique in the Académie Nationale de Médecine, Alfred Vulpian being the most notable. Pasteur's first studies on rabies are noted in his 1881 publication. But in 1885, he revealed that he had already immunized 50 dogs against rabies. Meanwhile, he was looking for human subjects. The most polemic of this search involves the second and last Emperor of Brazil, Dom Pedro II, who was a patron of the arts and sciences and followed and supported the work of the great scientist. During the reign of Dom Pedro II, the first Pasteur's Institute was founded in Rio de Janeiro, nine months before the Parisian, which had the financial support of Dom Pedro. This article deals with the interaction between the two outstanding characters, especially in the development of prophylactic treatment against rabies, and with the utilitarian aspects of this vaccine researches development against individual autonomy.

Prevalence of periodic limb movement in sleep in people with epilepsy: A semi-structured literature review.

OBJECTIVES: Epilepsy is a prevalent health problem worldwide in all ages, and it is essential to identify disease markers for diagnosis and treatment. Periodic limb movements in sleep (PLMS) are a common finding in polysomnography (PSG). Still, its clinical relevance in people with epilepsy (PWE) is unknown. The aim of this review was to compare PLMS frequency in PWE and controls. METHODS: A semi-structured literature review was conducted using PubMed in search of relevant studies in English on August 23, 2019, with the search terms "sleep," "epilepsy," or "seizure," and "polysomnography" in the title and/or abstract. The research was complemented with citation analysis and manual search using Google Scholar. Studies involved PWE and comparative controls using PSG with reported PLMS index (PLMI). RESULTS: Seven studies were identified. Only two showed a statistically significant difference in PLMI between cases and controls, and in another study, cases had uncontrolled seizures. In general, studies did not adjust for potential confounders including demographics, apnea-hypopnea index, or medication use. CONCLUSIONS: We found few studies exploring the prevalence of PLMS in PWE. In the majority, PLMI did not differ from controls. Further studies are warranted given the prevalence of sleep disturbances in epilepsy.

William Osler and Harvey Williams Cushing: Friendship Around Neurosurgery.

William Osler was a mentor for the younger William Harvey Cushing and they intermingled careers and friendship for the rest of their lives. They shared a common interest in the anatomy and pathology of neurological disorders, and in the history of medicine. Their behavior was, however, sharply different: Osler was the revered physician, full of wisdom and good humor, and Cushing, the prestigious surgeon, in a perennial and successful struggle to improve neurosurgery and himself. Both became medical icons, one beloved, and the other admired, each praised at their death centennial and 150 birth anniversary, respectively.

Jean-Alexandre Barré (1880-1967): his detection sign of subtle paresis due to pyramidal deficit (1919) and his work in line with that of Giovanni Mingazzini (1859-1929).

This is a paper about the development of a sensitive examination of subtle motor pyramidal deficits. Jean-Alexandre Barré's life and work are reappraised, and also his milieu prone to increase his clinical skillfulness and sharping many motor maneuvers on subtle motor deficits (1919, 1920, 1937). Giovanni Mingazzini is also remembered by his precursor publication of "small signs" about organic paresis (1913), and by his neuroanatomical background, in an Italian Neuropsychiatric milieu, at the time.

Sleep architecture in adults with epilepsy: a systematic review.

OBJECTIVES: To assess whether sleep architecture differs in subgroups of adults with epilepsy or in adults with epilepsy compared to control populations. METHODS: We completed a systematic review of papers published in two databases up to May 2018, with adults with epilepsy who have undergone either two consecutive nights of in-laboratory polysomnography (PSG) or one night of ambulatory PSG. Our review followed the PRISMA statements and guidelines and the protocol was registered in the PROSPERO platform prior to initiation of the review process (record CRD42018084009). RESULTS: Five studies out of 872 fulfilled our eligibility criteria. Only one study reported a significant difference in any sleep architecture parameter in group comparisons. Crespel et al., found that wake after sleep onset (WASO) time in minutes was higher in patients with refractory temporal lobe epilepsy when compared to refractory frontal lobe epilepsy (78.2 ± 5.3 vs. 28.1 ± 2.2; p < 0.01) and healthy controls (78.2 ± 5.3 vs. 27.9 ± 18.9; p < 0.007). CONCLUSIONS: Only a few studies objectively assessed sleep in adults with epilepsy while controlling for key factors that influence sleep. However, even those reports are heterogeneous in regards to methodology and population characteristics. Further studies are required to access the extent of sleep architectural abnormalities in adults with epilepsy.

Safety of repetitive transcranial magnetic stimulation in patients with epilepsy: A systematic review.

Approximately one-third of patients with epilepsy remain with pharmacologically intractable seizures. An emerging therapeutic modality for seizure suppression is repetitive transcranial magnetic stimulation (rTMS). Despite being considered a safe technique, rTMS carries the risk of inducing seizures, among other milder adverse events, and thus, its safety in the population with epilepsy should be continuously assessed. We performed an updated systematic review on the safety and tolerability of rTMS in patients with epilepsy, similar to a previous report published in 2007 (Bae EH, Schrader LM, Machii K, Alonso-Alonso M, Riviello JJ, Pascual-Leone A, Rotenberg A. Safety and tolerability of repetitive transcranial magnetic stimulation in patients with epilepsy: a review of the literature. Epilepsy Behav. 2007; 10 (4): 521-8), and estimated the risk of seizures and other adverse events during or shortly after rTMS application. We searched the literature for reports of rTMS being applied on patients with epilepsy, with no time or language restrictions, and obtained studies published from January 1990 to August 2015. A total of 46 publications were identified, of which 16 were new studies published after the previous safety review of 2007. We noted the total number of subjects with epilepsy undergoing rTMS, medication usage, incidence of adverse events, and rTMS protocol parameters: frequency, intensity, total number of stimuli, train duration, intertrain intervals, coil type, and stimulation site. Our main data analysis included separate calculations for crude per subject risk of seizure and other adverse events, as well as risk per 1000 stimuli. We also performed an exploratory, secondary analysis on the risk of seizure and other adverse events according to the type of coil used (figure-of-8 or circular), stimulation frequency (≤ 1 Hz or > 1 Hz), pulse intensity in terms of motor threshold (<100% or ≥ 100%), and number of stimuli per session (< 500 or ≥ 500). Presence or absence of adverse events was reported in 40 studies (n = 426 subjects). A total of 78 (18.3%) subjects reported adverse events, of which 85% were mild. Headache or dizziness was the most common one, occurring in 8.9%. We found a crude per subject seizure risk of 2.9% (95% CI: 1.3-4.5), given that 12 subjects reported seizures out of 410 subjects included in the analysis after data of patients with epilepsia partialis continua or status epilepticus were excluded from the estimate. Only one of the reported seizures was considered atypical in terms of the clinical characteristics of the patients' baseline seizures. The atypical seizure happened during high-frequency rTMS with maximum stimulator output for speech arrest, clinically arising from the region of stimulation. Although we estimated a larger crude per subject seizure risk compared with the previous safety review, the corresponding confidence intervals contained both risks. Furthermore, the exclusive case of atypical seizure was the same as reported in the previous report. We conclude that the risk of seizure induction in patients with epilepsy undergoing rTMS is small and that the risk of other adverse events is similar to that of rTMS applied to other conditions and to healthy subjects. Our results should be interpreted with caution, given the need for adjusted analysis controlling for potential confounders, such as baseline seizure frequency. The similarity between the safety profiles of rTMS applied to the population with epilepsy and to individuals without epilepsy supports further investigation of rTMS as a therapy for seizure suppression.

A neurological bias in the history of hysteria: from the womb to the nervous system and Charcot / Um viés neurológico na história da histeria: desde o útero até o sistema nervoso e Charcot

Hysteria conceptions, from ancient Egypt until the 19th century Parisian hospital based studies, are presented from gynaecological and demonological theories to neurological ones. The hysteria protean behavioral disorders based on nervous origin was proposed at the beginning, mainly in Great Britain, by the “enlightenment nerve doctors”. The following personages are highlighted: Galen, William, Sydenham, Cullen, Briquet, and Charcot with his School. Charcot who had hysteria and hypnotism probably as his most important long term work, developed his conceptions, initially, based on the same methodology he applied to studies of other neurological disorder. Some of his associates followed him in his hysteria theories, mainly Paul Richer and Gilles de La Tourette who produced, with the master's support, expressive books on Salpêtrière School view on hysteria.

As concepções da histeria, desde o antigo Egito até os estudos baseados nos hospitais parisienses do século 19 são apresentados, a partir de teorias ginecológicas e demonológicas até às neurológicos. A ideia dos transtornos comportamentais multiformes com base na origem nervosa foi proposta no início, principalmente na Grã-Bretanha, pelos “médicos dos nervos do iluminismo”. Os seguintes personagens se destacam: Galeno, William, Sydenham, Cullen, Briquet e Charcot com a sua escola. Charcot tinha a histeria e hipnose provavelmente como o seu trabalho mais importante a longo prazo. Ele desenvolveu suas concepções inicialmente com base na mesma metodologia aplicada a estudos sobre outros transtornos neurológicos. Alguns de seus associados seguiram-no em suas teorias, principalmente Paul Richer e Gilles de La Tourette, que produziram, com o apoio do mestre, livros significativos da Escola da Salpêtrière sobre a histeria.

Quality of life among Brazilian children with epilepsy: validation of a parent proxy instrument (QVCE-50).

PURPOSE: To analyze the validity and reliability of an epilepsy specific health related quality of life (HRQL) instrument (QVCE-50), constructed for Brazilians. The QVCE-50 comprises the following domains: physical (9 items), psychological (18 items), social/familial (7 items), and cognitive/educational (16 items). Items were scored on a four point scale. Domains were equally weighted using percent scores. The questionnaire ends with a quality of life scale scored 0-10 and a space for free observations. METHODS: A total of 77 children with epilepsy were consecutively seen in a neuropaediatric ambulatory unit. Parents or caregivers responded to the QVCE-50 and a Portuguese version of ICIS (Impact of Childhood Illness Scale). QVCE-50 was analyzed for internal consistency, reliability, content and concurrent validity. Clinical and socio-demographic variables were also analyzed. RESULTS: Socio-demographic and clinical variables that differed in at least one domain were age, sex, time since diagnosis, epilepsy family history, and antiepileptic drug used. Internal consistency, analyzed by Cronbach's alpha, showed good results for total and domain scores: physical (0.68), psychological (0.86), socio-familiar (0.70) and cognitive-educational (0.91). Total scores on the QVCE-50 and ICIS are inversely correlated (Pearson's r=-0.74, p<0.0001). The Intraclass Correlation Coefficients for test-retest reliability were acceptable: physical (0.51), psychological (0.62), socio-familiar (0.66), cognitive-educational (0.85) and total (0.77), p<0.0001. CONCLUSIONS: QVCE-50 has good psychometric properties. It is a useful tool for analyzing HRQL in children with epilepsy for Portuguese speakers, especially Brazilians. Other properties should be further tested, such as responsiveness to drug and surgical treatment, capacity of distinguishing among seizure control categories and etiology (with a larger sample) and impact of psychiatric and cognitive co-morbidities.