Rett syndrome: the Brazilian contribution to the gene discovery / Síndrome de Rett: a contribuição brasileira para a descoberta do gene

ABSTRACT A brief history of the syndrome discovered by Andreas Rett is reported in this paper. Although having been described in 1966, the syndrome was only recognized by the international community after a report by Hagberg et al. in 1983. Soon, its importance was evident as a relatively frequent cause of severe encephalopathy among girls. From the beginning it was difficult to explain the absence of male patients and the almost total predominance of sporadic cases (99%), with very few familial cases. For these reasons, it was particularly difficult to investigate this condition until 1997, when a particular Brazilian family greatly helped in the final discovery of the gene, and in the clarification of its genetic mechanism. Brief references are made to the importance of the MECP2 gene, 18 years later, as well as to its role in synaptogenesis and future prospects.

RESUMO Uma breve história de uma síndrome neurológica descoberta por Andreas Rett é relatada neste artigo. Embora tenha ocorrido em 1966, a síndrome só foi reconhecida pela comunidade internacional após um relato de Hagberget al, em 1983. Logo, sua importância ficou evidente como causa relativamente frequente de encefalopatia grave entre as crianças do sexo feminino. Desde o início, foi difícil explicar a ausência de envolvimento de pacientes do sexo masculino e a quase absoluta preponderância de casos esporádicos (99%), com muitos poucos casos familiares. Por essas razões, foi difícil investigar essa condição até 1997, quando uma família brasileira em particular ajudou muito na descoberta final do gene e no esclarecimento de seu mecanismo genético. São feitas referências sucintas à importância do gene MECP2, dezoito anos depois, bem como ao seu papel na sinaptogênese e nas perspectivas futuras.

Rett syndrome: the Brazilian contribution to the gene discovery.

OBJECTIVE: A brief history of the syndrome discovered by Andreas Rett is reported in this paper. METHODS: Although having been described in 1966, the syndrome was only recognized by the international community after a report by Hagberg et al. in 1983. Soon, its importance was evident as a relatively frequent cause of severe encephalopathy among girls. CONCLUSION: From the beginning it was difficult to explain the absence of male patients and the almost total predominance of sporadic cases (99%), with very few familial cases. For these reasons, it was particularly difficult to investigate this condition until 1997, when a particular Brazilian family greatly helped in the final discovery of the gene, and in the clarification of its genetic mechanism. RESULTS: Brief references are made to the importance of the MECP2 gene, 18 years later, as well as to its role in synaptogenesis and future prospects.

Aristides Leão: a birth centennial homage with comments on his spreading depression.

The year of 2014 is the birth centenary of Aristides Azevedo Pacheco Leão (1914-1993), and also marks seventy years of the publication of his discovery of the novel electrophysiological phenomenon, named by him "spreading depression" (SD), soon designated "Leão's wave" or "Leão's spreading depression". This was a remarkable scientific milestone, and the author must be celebrated for this achievement, as the studies he triggered proceeded worldwide, with new concepts, as spreading depolarization, until the present days. Robust experimental and clinical evidence emerged to suggest that these and related electrophysiological phenomena are involved in the mechanisms of migraine aura, acute cerebrovascular diseases, traumatic brain injury, transient global amnesia, epileptic seizures, and their pathophysiological characteristics come to offer new therapeutic perspectives. He was a remarkable and complex personality, and the authors remit the readers to a paper where his personal life is contemplated.

Aristides Leão: a birth centennial homage with comments on his spreading depression / Aristides Leão: homenagem ao centenário de nascimento com comentários sobre sua depressão alastrante

The year of 2014 is the birth centenary of Aristides Azevedo Pacheco Leão (1914-1993), and also marks seventy years of the publication of his discovery of the novel electrophysiological phenomenon, named by him “spreading depression” (SD), soon designated “Leão’s wave” or “Leão’s spreading depression”. This was a remarkable scientific milestone, and the author must be celebrated for this achievement, as the studies he triggered proceeded worldwide, with new concepts, as spreading depolarization, until the present days. Robust experimental and clinical evidence emerged to suggest that these and related electrophysiological phenomena are involved in the mechanisms of migraine aura, acute cerebrovascular diseases, traumatic brain injury, transient global amnesia, epileptic seizures, and their pathophysiological characteristics come to offer new therapeutic perspectives. He was a remarkable and complex personality, and the authors remit the readers to a paper where his personal life is contemplated.

O ano de 2014 é o centenário de nascimento de Aristides Azevedo Pacheco Leão (1914-1993), e também assinala setenta anos da publicação de sua descoberta, que ele denominou “depressão alastrante” (DA), logo designada “onda de Leão” ou “depressão alastrante de Leão”. Foi um notável marco científico e o autor deve ser celebrado por esse feito, considerando que estudos que desencadeou continuaram no mundo todo, com novos conceitos, como a despolarização alastrante, até os dias atuais. Evidência experimental e clínica robusta emergiram sugerindo que esses fenômenos eletofisiológicos e outros relacionados encontram-se envolvidos nos mecanismos da aura da enxaqueca, doenças cerebrovasculares agudas, lesão cerebral traumática, amnésia global transitória, crises epiléticas, sendo que suas características fisiopatológicas vêm oferecer novas perspectivas terapêuticas. Foi uma personalidade complexa e notável, e os autores remetem os leitores para um artigo no qual sua vida pessoal é contemplada.

[History of cranial surgery, cerebral tumor surgery and epilepsy surgery in Mexico]. / Historia de la cirugía de cráneo, de los tumores cerebrales y de la epilepsia en México.

The first report of intra-cerebral tumor surgery was provided by Bennett & Goodle, in London, 1884. Worldwide this kind of surgery was performed in France by Chipault, in Italy by Durante, in the United States by Keen and in Deutchland by Krause & Oppenheim. Lavista in Mexico City operated on intra-cerebral tumor in 1891, and the report was printed in 1892. In the same publication, Lavista exhibited the first cases of epilepsy surgery. Since now, it is the first report of this kind of surgery in the Spanish-speaking world.

Dom João VI's death: convulsions and coma

Dom João VI's death occurred in adverse political conditions that led to the regicide hypothesis. The main aim of this paper is to mention life style and conditions of the death of the king by means of narrative review based on primary and secondary sources. Dom João VI died in the way of convulsions and gastrointestinal symptoms. This could be the result of the pathological chain of genetic determination, accentuated by the inappropriate life style, obesity and sedentary habits, and/or poisoning. The finding of arsenic in high doses in his viscera favors the last hypothesis as the basic cause of death, but one can not discard the atherosclerosis predisposing risk factors for a final stroke.

A morte de Dom João VI aconteceu em condições políticas adversas que conduziram à hipótese de regicídio. O objetivo principal deste artigo é mencionar o estilo de vida e condições da morte do rei por meio de revisão narrativa baseada em fontes primárias e secundárias. Dom João VI morreu apresentando convulsões e sintomas gastrointestinais. Esse poderia ser o resultado da cadeia patológica de determinação genética, acentuada pelo estilo de vida inapropriado, obesidade e/ou envenenamento. O achado de arsênico em doses altas nas suas vísceras aponta a última hipótese como a causa básica da morte, mas não se pode descartar a aterosclerose como fator de risco predisponente para um acidente vascular cerebral final.

Dom João VI's death: convulsions and coma.

Dom João VI's death occurred in adverse political conditions that led to the regicide hypothesis. The main aim of this paper is to mention life style and conditions of the death of the king by means of narrative review based on primary and secondary sources. Dom João VI died in the way of convulsions and gastrointestinal symptoms. This could be the result of the pathological chain of genetic determination, accentuated by the inappropriate life style, obesity and sedentary habits, and/or poisoning. The finding of arsenic in high doses in his viscera favors the last hypothesis as the basic cause of death, but one can not discard the atherosclerosis predisposing risk factors for a final stroke.

Cerebral systems in the pathogenesis of endogenous psychoses. 1974.

Mental process imply a harmonious functioning of psychic systems, assembled into larger units, psychic spheres (Table 1). Their neurophysiological representatives are brain systems of areas and pathways (Figs 1-4). Under functional and/or organic disturbances these systems originate the leading mental symptoms (Table 2) characterizing the diverse endogenous psychoses: hence, the latter's distinctive patterns. Accordingly, understanding and classification of psychoses should rest on the pathogenic dynamisms, not on clinical description. This is why Kleist's and Leonhard's conceptions of the endogenous psychoses surpass any other to exist. Kleist stands among the founders of psychiatry, by describing the "degeneration psychoses" and many single psychoses, as well as redefining, isolating and clarifying the progressive ones, later on renamed as schizophrenias (Table 3). Such pathogenic criterion may also be useful to define mental conditions other than psychoses, as hysteria, neuroses and psychopathic inferiority (Tables 4 and 5). One should consider here, besides the psychic systems and spheres involved, the way they were caught and the corresponding developmental phase. In Kleist's "degeneration psychoses"--cyclic or episodic (Table 6) the systems and spheres are disturbed by functional transient processes due to latent dispositions, while his and Leonhard's schizophrenias (Table 7) show a rather progressive, deteriorating course. The nature of the disorder is itself genetically determined, as is either its confinement to one sphere or its spreading out. The spread out pattern, while exceptional in schizophrenia, represents a rule for the "degeneration psychoses", in discussant's mind. Both groups may have symptoms alike by involvement of the same sphere (Table 8), but proper diagnosis is reached by taking pathogenesis into consideration.

The neuropathology of South American mummies.

Few studies of intracranial mummified brain tissue have been undertaken. This is because of the infrequency in which preserved human central nervous system tissue is encountered and the scarcity of available mummies from different parts of the world. This study undertook a systematic analysis of 15 naturally mummified human brains from 1000 B.C. to 1500 A.D. excavated from the deserts of northern Chile. Gross examination revealed relatively well-preserved dura mater, cerebral hemispheres, cerebellum, and spinal cord in several cases. Five cases showed evidence of intracranial disease. Three cases had evidence of external injury. One case revealed subarachnoid and one case revealed intracerebral hemorrhage. Samples of central nervous system tissues were taken for further analysis. The samples were rehydrated and processed for structural analysis by light and electron microscopy. Light microscopy of the brain parenchyma revealed an eosinophilic staining background with vascular structures but few cellular elements present. The dura mater demonstrated normal dural architecture consisting of collagen fibrils. Electron microscopy did not clearly demonstrate individual neurons or axonal processes. Bundles of collagen fibrils with typical periodicity were clearly seen in the dura mater. The examination of ancient human central nervous system tissues reveals normal and abnormal neuroanatomy.