Long-term clinical observation of patients with heterozygous KIF1A variants.

KIF1A-related disorders (KRDs) encompass recessive and dominant variants with wide clinical variability. Recent genetic investigations have expanded the clinical phenotypes of heterozygous KIF1A variants. However, there have been a few long-term observational studies of patients with heterozygous KIF1A variants. A retrospective chart review of consecutive patients diagnosed with spastic paraplegia at Miyagi Children's Hospital from 2016 to 2020 identified six patients with heterozygous KIF1A variants. To understand the long-term changes in clinical symptoms, we examined these patients in terms of their characteristics, clinical symptoms, results of electrophysiological and neuroimaging studies, and genetic testing. The median follow-up period was 30 years (4-44 years). This long-term observational study showed that early developmental delay and equinus gait, or unsteady gait, are the first signs of disease onset, appearing with the commencement of independent walking. In addition, later age-related progression was observed in spastic paraplegia, and the appearance of axonal neuropathy and reduced visual acuity were characteristic features of the late disease phenotype. Brain imaging showed age-related progression of cerebellar atrophy and the appearance of hyperintensity of optic radiation on T2WI and FLAIR imaging. Long-term follow-up revealed a pattern of steady progression and a variety of clinical symptoms, including spastic paraplegia, peripheral neuropathy, reduced visual acuity, and some degree of cerebellar ataxia. Clinical variability between patients was observed to some extent, and therefore, further studies are required to determine the phenotype-genotype correlation.

The Clinical Course and Treatment of a Case of Refractory Systemic Juvenile Myasthenia Gravis Successfully Treated with Thymectomy.

Juvenile myasthenia gravis (JMG) exhibits a more favorable response to glucocorticoids and has a better prognosis than adult myasthenia gravis. However, no established treatment exists for refractory JMG. Although thymectomy has been performed in several patients with refractory systemic JMG, there are few detailed clinical descriptions of patients who underwent thymectomy. Here, we present the case of a 10-year-old boy with refractory systemic JMG who was successfully treated with thymectomy. The patient developed symptoms, including dysphagia, malaise, diurnal ptosis, and weakness in the trunk muscles, and he was diagnosed with generalized JMG. Despite undergoing various treatments, including steroids, tacrolimus, steroid pulse therapy, intravenous immunoglobulin, azathioprine (AZT), and rituximab, his symptoms did not improve. Therefore, he underwent a thoracoscopic thymectomy 24 months after disease onset. Thymectomy led to remission, as demonstrated by a significant reduction in the quantitative myasthenia gravis score and anti-acetylcholine receptor antibody levels, which persisted for 43 months after surgery. Our case demonstrates the effectiveness of thymectomy in systemic JMG patients with positive anti-acetylcholine receptor antibodies, despite therapeutic failure with AZT and rituximab, within 2 years of disease onset.

Multiple Cerebral Hemorrhages and White Matter Lesions Developing after Severe hMPV Pneumonia in a Patient with Trisomy 13: A Case Report and Review of the Literature.

Human metapneumovirus (hMPV) is a common cause of upper and lower respiratory tract infections in children. A few case reports have described hMPV encephalitis or encephalopathy. Neuroimaging data on patients with hMPV encephalitis are scarce. We report a patient with trisomy 13 who developed severe hMPV pneumonia, multifocal cerebral and cerebellar hemorrhagic infarctions and extensive cerebral white matter demyelination. Although adult respiratory distress syndrome and disseminated intravascular coagulation contributed to the devastating central nervous system (CNS) lesions, endothelial dysfunction of the CNS caused by hMPV infection probably also played a pathophysiological role in this case.

Two Siblings with Cerebellar Ataxia, Mental Retardation, and Disequilibrium Syndrome 4 and a Novel Variant of ATP8A2.

Cerebellar ataxia, mental retardation, and disequilibrium syndrome 4 (CAMRQ4) is early onset neuromotor disorder and intellectual disabilities caused by variants of ATP8A2. We report sibling cases and systematically analyze previous literature to increase our understanding of CAMRQ4. Japanese siblings presented with athetotic movements at 1 and 2 months of age. They also had ptosis, ophthalmoplegia, feeding difficulty, hypotonia, and severely delayed development. One patient had retinal degeneration and optic atrophy. Flattening of the auditory brainstem responses and areflexia developed. At the last follow-up, neither patient could sit or achieve head control, although some nonverbal communication was preserved. Whole exome sequencing revealed compound heterozygous variants of ATP8A2: NM_016529.6:c.[1741C>T];[2158C>T] p.[(Arg581*)];[(Arg720*)]. The p.(Arg581*) variant has been reported, while the variant p.(Arg720*) was novel. The symptoms did not progress in the early period of development, which makes it difficult to distinguish from dyskinetic cerebral palsy, particularly in solitary cases. However, visual and hearing impairments associated with involuntary movements and severe developmental delay may be a clue to suspect CAMRQ4.

[Sick leave-related factors and quality of life in Japanese working cancer patients receiving outpatient treatment].

Objective　This study aimed (1) to clarify sick leave-related factors in Japanese working cancer patients receiving outpatient treatment and (2) to assess quality of life (QOL) in this group of patients.Methods　A survey was conducted using a questionnaire designed for adult cancer patients aged 20 to 64 years who were currently receiving outpatient treatment and living in Hokkaido. The questionnaire was used to collect data on basic characteristics, cancer-related factors, and QOL (SF-12v2, Japanese edition). To clarify the factors related to sick leave, we first calculated the propensity score using logistic regression analysis. The presence or absence of sick leave was the dependent variable, and the basic attributes were the covariates. We then analyzed each variable with significant differences in basic and cancer-related attributes as an independent variable using binomial logistic regression analysis. Quality of life was evaluated by comparing scores on the eight subscales and three component summaries of the SF-12v2.Results　There were a total of 147 respondents, of which 79 were included in this study. They were classified into two groups: the leave group (29, 36.7%) and the work continuation group (50, 63.3%). The logistic regression analysis with propensity score adjustment showed that taking leave were associated with patients who were less than 6 months since cancer diagnosis (odds ratio=17.9, P<0.001) and patients who had not undergone surgery (odds ratio=3.9, P=0.011). The QOL scores of the leave group were lower than those of the Japanese national sample in seven out of the eight subscales, and there was a significant decrease in the six items for the work continuation group. In particular, two role functioning dimensions-physical and emotional-were remarkably decreased. In the analysis of component summary scores, it was found that QOL scores of cancer patients were lower for the role component summary (RCS) and physical component summary (PCS) compared with the national samples; however, mental component summary scores showed an increasing trend. The leave group had significantly lower RCS and PCS scores compared with the work continuation group.Conclusion　We surveyed Japanese working cancer patients and analyzed sick leave-related factors and QOL in that population. We found that having less than 6 months since cancer diagnosis and not having undergone surgery were highly related to leave, and QOL scores (RCS and PCS) were low. The results of this study indicate that Japanese working cancer patients need to be provided with support that is based on their specific characteristics.

Neonatal developmental and epileptic encephalopathy with movement disorders and arthrogryposis: A case report with a novel missense variant of SCN1A.

Variants of SCN1A represent the archetypal channelopathy associated with several epilepsy syndromes. The clinical phenotypes have recently expanded from Dravet syndrome. CASE REPORT: We present a female patient with the de novo SCN1A missense variant, c.5340G > A (p. Met1780Ile). The patient had various clinical features with neonatal onset SCN1A epileptic encephalopathy, arthrogryposis multiplex congenita, thoracic hypoplasia, thoracic scoliosis, and hyperekplexia. CONCLUSION: Our findings are compatible with neonatal developmental and epileptic encephalopathy with movement disorders and arthrogryposis; the most severe phenotype probably caused by gain-of-function variant of SCN1A. The efficacy of sodium channel blocker was also discussed. Further exploration of the phenotype-genotype relationship of SCN1A variants may lead to better pharmacological treatments and family guidance.

Slave mortality during the cholera epidemic in Rio de Janeiro (1855-1856): a preliminary analysis. / Mortalidade escrava durante a epidemia de cólera no Rio de Janeiro (1855-1856): uma análise preliminar.

The article offers a preliminary analysis of the sociodemographic profile of deaths recorded during the first cholera epidemic in Rio de Janeiro, based on data gathered from death records at Santa Casa de Misericórdia Hospital. After cholera appeared in the country in 1855, Brazilian medical reports indicated a social bias, with slaves and the free poor suffering high mortality. From a historical perspective, however, little research has been done on the epidemic and its dynamics. The recovery of original data on cholera and the analysis of cholera mortality rates help us to better understand aspects of the slave universe in the urban zone of Rio de Janeiro in the period following the end of the slave trade.

The art of giving birth to a graduate program in history: on the 20th anniversary of the Graduate Program in the History of the Sciences and Health: interview with Margarida de Souza Neves. / A arte de partejar um programa de pós-graduação em história: os 20 anos do Programa de Pós-graduação em História das Ciências e da Saúde: entrevista com Margarida de Souza Neves.

This interview explores the participation of Margarida de Souza Neves, professor emeritus at Pontifícia Universidade Católica do Rio de Janeiro, in the creation of the Graduate Program in the History of the Sciences and Health at Casa de Oswaldo Cruz. To celebrate the twentieth anniversary of this graduate program, professors who have served as coordinators met with Professor Neves to reflect on the meanings of shaping a program in the area of history specializing in research on science and health in Brazil.

A entrevista aborda a participação de Margarida de Souza Neves, professora emérita da Pontifícia Universidade Católica do Rio de Janeiro, na criação do Programa de Pós-graduação em História das Ciências e da Saúde da Casa de Oswaldo Cruz. Para celebrar os 20 anos de existência do PPGHCS, professores que passaram pela coordenação se reúnem com a entrevistada para refletir sobre os significados da formação de um programa na área de história especializado em pesquisas sobre ciências e saúde no Brasil.

A patient with early-onset SMAX3 and a novel variant of ATP7A.

OBJECTIVE: To describe clinical and genetic studies on a patient with early-onset spinal muscular atrophyX3 (SMAX3) with novel variant of ATP7A. METHODS: Clinical, neurophysiological, neuroimaging and pathological examinations were performed. Whole exome sequencing was applied to search genetic bases of this patient. RESULTS: The patient had gait abnormality from early infantile period. Muscle imaging at 42 years old showed predominant involvement of proximal muscles as compared to the distal muscles. The patient had a novel variant of ATP7A, which was the fourth genotype of ATP7A exhibited as SMAX3. Contrary to previous reports of distal motor neuropathy, the clinical and neuroimaging findings in this case revealed dominant involvement in the proximal portion of the extremities and trunk, which is similar to patients with type III SMA. CONCLUSION: The dominant involvement of proximal motor system in this patient may expand the phenotypic variability of SMAX3. We need to be aware of this disorder in differential diagnosis of patients with type III SMA-like phenotype.

Reduced efficacy of perampanel in patients with severe motor and intellectual disabilities syndrome and drug-resistant epilepsy: A single-center analysis from Japan.

People with severe motor and intellectual disabilities syndrome (SMIDS) have multiple comorbidities and high mortality rates. This study examined whether there is a difference in the efficacy and tolerability of perampanel (PER) between patients with drug-resistant epilepsy with or without SMIDS. The study identified 65 patients with drug-resistant epilepsy who underwent PER treatment as adjunctive therapy. The 50 % responder rate was 22 % (14/65) overall and 11 % (5/44) in patients with SMIDS versus 43 % (9/21) in patients without SMIDS (p <0.01). Although the overall 50 % responder rate was similar to those of previous reports, PER was less efficacious in the patients with SMIDS; nevertheless, PER was tolerated in the patients with SMIDS.

A 23-year follow-up report of juvenile-onset Sandhoff disease presenting with a motor neuron disease phenotype and a novel variant.

BACKGROUND: The clinical severity of Sandhoff disease is known to vary widely. Furthermore, long-term follow-up report is very limited in the literature. CASE PRESENTATION: We present a long-term follow-up report of a patient with juvenile-onset Sandhoff disease with a motor neuron disease phenotype. The patient had compound heterozygous variants of HEXB (p.Trp460Arg, p. Arg533His); the Trp460Arg was a novel variant. Long-term follow-up revealed no intellectual deterioration, swallowing dysfunction, or respiratory muscle dysfunction despite progressive weakness of the extremities and sensory disturbances. CONCLUSION: We need to be aware of Sandhoff disease in patients with juvenile-onset motor neuron disease.

A arte de partejar um programa de pós-graduação em história: os 20 anos do Programa de Pós-graduação em História das Ciências e da Saúde: entrevista com Margarida de Souza Neves / The art of giving birth to a graduate program in history: on the 20th anniversary of the Graduate Program in the History of the Sciences and Health: interview with Margarida de Souza Neves

Resumo A entrevista aborda a participação de Margarida de Souza Neves, professora emérita da Pontifícia Universidade Católica do Rio de Janeiro, na criação do Programa de Pós-graduação em História das Ciências e da Saúde da Casa de Oswaldo Cruz. Para celebrar os 20 anos de existência do PPGHCS, professores que passaram pela coordenação se reúnem com a entrevistada para refletir sobre os significados da formação de um programa na área de história especializado em pesquisas sobre ciências e saúde no Brasil.

Abstract This interview explores the participation of Margarida de Souza Neves, professor emeritus at Pontifícia Universidade Católica do Rio de Janeiro, in the creation of the Graduate Program in the History of the Sciences and Health at Casa de Oswaldo Cruz. To celebrate the twentieth anniversary of this graduate program, professors who have served as coordinators met with Professor Neves to reflect on the meanings of shaping a program in the area of history specializing in research on science and health in Brazil.

Mortalidade escrava durante a epidemia de cólera no Rio de Janeiro (1855-1856): uma análise preliminar / Slave mortality during the cholera epidemic in Rio de Janeiro (1855-1856): a preliminary analysis

Apresenta uma primeira análise do perfil sociodemográfico dos óbitos registrados durante a primeira epidemia de cólera no Rio de Janeiro, a partir de dados coletados nos registros de óbito da Santa Casa de Misericórdia. Desde a manifestação do cólera, em 1855, relatos médicos brasileiros apontam seu viés social, que, no caso do país, implicava a alta mortalidade de escravos e livres pobres. Do ponto de vista histórico, entretanto, a epidemia e sua dinâmica foram pouco estudadas. A recuperação de dados originais sobre o cólera e a análise das taxas de mortalidade associadas à doença auxiliam-nos a melhor compreender aspectos do universo escravo na zona urbana da cidade, no período subsequente ao fim do tráfico negreiro. (AU)

Mortalidade escrava durante a epidemia de cólera no Rio de Janeiro (1855-1856): uma análise preliminar / Slave mortality during the cholera epidemic in Rio de Janeiro (1855-1856): a preliminary analysis

Apresenta uma primeira análise do perfil sociodemográfico dos óbitos registrados durante a primeira epidemia de cólera no Rio de Janeiro, a partir de dados coletados nos registros de óbito da Santa Casa de Misericórdia. Desde a manifestação do cólera, em 1855, relatos médicos brasileiros apontam seu viés social, que, no caso do país, implicava a alta mortalidade de escravos e livres pobres. Do ponto de vista histórico, entretanto, a epidemia e sua dinâmica foram pouco estudadas. A recuperação de dados originais sobre o cólera e a análise das taxas de mortalidade associadas à doença auxiliam-nos a melhor compreender aspectos do universo escravo na zona urbana da cidade, no período subsequente ao fim do tráfico negreiro.

The article offers a preliminary analysis of the sociodemographic profile of deaths recorded during the first cholera epidemic in Rio de Janeiro, based on data gathered from death records at Santa Casa de Misericórdia Hospital. After cholera appeared in the country in 1855, Brazilian medical reports indicated a social bias, with slaves and the free poor suffering high mortality. From a historical perspective, however, little research has been done on the epidemic and its dynamics. The recovery of original data on cholera and the analysis of cholera mortality rates help us to better understand aspects of the slave universe in the urban zone of Rio de Janeiro in the period following the end of the slave trade.

Os estudos etnográficos no Instituto Histórico e Geográfico Brasileiro (1840-1860): história, viagens e questão indígena / The ethnographic studies of the Instituto Histórico e Geográfico Brasileiro (1840-1860): history, travels and indigenous question

O artigo aborda a etnografia do Instituto Histórico e Geográfico Brasileiro (IHGB) em meados do século XIX, dando destaque à produção etnográfica do sócio da instituição, Antônio Gonçalves Dias. Chama a atenção para alguns aspectos que caracterizaram os estudos indígenas do momento: a visão dicotômica entre índios do passado e índios do presente que se desdobrava na percepção dos grupos de origem tupi e os 'tapuias', conhecidos também como não falantes do tupi ou índios do sertão; e a dependência da disciplina etnográfica do campo da história, então em pleno desenvolvimento no IHGB. Tais aspectos, que invariavelmente anunciavam uma perspectiva 'decadentista' sobre os índios, repercutiram nas ações políticas que os envolveram no período e, ao mesmo tempo, impossibilitaram a percepção da imensa variabilidade étnica existente no interior do Brasil, quando os intelectuais da instituição seguiram em viagem às províncias do Norte. Não obstante o anúncio constante do desaparecimento dos índios, algum legado dessa viagem permite entrever a riqueza do material coletado junto àquelas populações, que, sob formas distintas de presença na atualidade, continuam a nos fornecer reflexões sobre a complexidade da formação nacional.(AU)

The article examines the ethnography of the Instituto Histórico e Geográfico Brasileiro (IHGB) in the mid-19th century, highlighting the ethnographic production of its member, Antônio Gonçalves Dias. It emphasizes some of the aspects which characterized the indigenous studies at that moment: the dichotomous image between the Indians of the past and the Indians of the present that echoed in the perception of the Tupi groups and the Tapuia, known as the non-speaking Tupi language groups or the Indians of the hinterland; and the subjection of ethnography to the field of history, as developed in the IHGB. These aspects were related to the theories about the 'decadence' of the Indians and directly affected both the way the Indigenous policies were built and the incapacity of Brazilian intellectuals to assess the ethnic diversity, when some of the IHGB members travelled to the northern provinces of Brazil. Although the Indians extinction was constantly announced, the legacy of this expedition allows glimpsing the richness of the material collected within the indigenous peoples, which continues to challenge in different ways considerations about the complexity of Brazilian national formation.(AU)

Antiescravismo e epidemia: "O tráfico dos negros considerado como a causa da febre amarela", de Mathieu François Maxime Audouard, e o Rio de Janeiro em 1850 / Antislavery and epidemic Mathieu François Maxime Audouard's "O tráfico dos negros considerado como a causa da febre amarela" and the city of Rio de Janeiro in 1850

O artigo "O tráfico dos negros considerado como a causa da febre amarela", de Mathieu François Maxime Audouard (1776-1856), foi publicado em 1850 no jornal O Philantropo, periódico de propaganda contra o tráfico que circulou no Rio de Janeiro entre 1849 e 1852, e contava com diversos médicos entre seus membros. O texto, traduzido do original do médico francês e publicado no contexto da epidemia de febre amarela na cidade, oferece elementos para refletir sobre a atuação dos médicos brasileiros na questão da escravidão, no momento em que era promulgada a cessação do tráfico no país.

The article "O tráfico de negros considerado como a causa da febre amarela" [The Negro slave trade considered as the cause of yellow fever] , by French physician Mathieu François Maxime Audouard (1776-1856), was published in 1850 in the newspaper O Philantropo, an organ of anti-slave trade propaganda that circulated in Rio de Janeiro from 1849 to 1852, with a number of physicians as members. Translated from the original and published during the yellow fever epidemic that hit Rio de Janeiro, the text affords an opportunity to reflect on the positions about slavery that were held by Brazilian physicians at the time the law against the slave trade was promulgated in Brazil.

O doutor Audouard em Barcelona (1821) e a repercussão de sua tese sobre a febre amarela no Brasil / Dr. Audouard in Barcelona (1821) and the repercussion of his thesis on yellow fever in Brasil

O artigo pretende analisar parte dos trabalhos do médico militar francês Mathieu François Maxime Audouard, que observara a epidemia de febre amarela em Barcelona em 1821. Audouard passaria a acusar o tráfico negreiro como principal causa da doença. Embora suas idéias fossem controversas e nem sempre aceitas pelos médicos de diferentes partes do mundo, elas apresentaram repercussão entre aqueles engajados no fim do tráfico e no movimento contra a escravidão da primeira metade do século XIX. Um caso de particular interesse para análise é a recepção de seus trabalhos no Brasil, frente ao momento de fim do tráfico negreiro no país, e a concomitância com a chegada da grande epidemia de febre amarela. (AU)

Os debates pelo fim do tráfico no periódico O Philantropo (1849-1852) e a formação do povo: doenças, raça e escravidão / The debate on the end of the slave trade in the periodical O Philantropo (1849-1852) and the formation of the people: illnesses, race and slavery

O propósito deste artigo é investigar a atuação do jornal O Philantropo (1849-1852), bem como da "Sociedade contra o Tráfico de Africanos e Promotora da Colonisação e da Civilização dos Indígenas", que sustentou o jornal. Procura-se atentar para a especificidade dos segmentos presentes na Sociedade em relação ao projeto de fim do tráfico, no momento em que ocorriam os debates no Parlamento. No jornal, a bandeira antitráfico combinava em suas propostas a defesa da mão-de-obra livre e um nacionalismo que muitas vezes lançava mão de argumentos racialistas. Interessa-nos, assim, destacar aspectos do debate da Sociedade através de um exame do perfil de seus sócios e na articulação que apresentaram entre as questões da colonização e da formação do povo, através dos temas da raça, das doenças e da escravidão.(AU)

This paper aims at investigating the newspaper O Philantropo (1849-1852) and the Society against the Slave Trade and for the Colonization and Civilization of the Indians which supported it. It focuses on the specific roles of the Society's members in the movement for ending the slave trade, when the discussion for its suppression was taking place in Parliament. In the newspaper, ranged under the banner of the defense against the slave trade, could also be found the support for a free labor force and a nationalism which frequently made use of racialist arguments. It attempts to detach some aspects of the debate of the Society by examining the profile of its members as well as by articulating the problem of colonization with the formation of the nation through the issues of race, diseases and slavery.(AU)