Adults with tuberous sclerosis complex: A distinct patient population.

OBJECTIVES: There are few data on adults living with tuberous sclerosis complex (TSC), with most studies focusing on pediatric populations. The objective of our study was to examine a large national cohort of adults with TSC, and to describe the clinical characteristics of these adults and the nature of the multidisciplinary care that they receive. METHODS: Six Canadian medical centers collaborated in this study. Data were collected using a standardized form, and descriptive statistics were used for the analyses. RESULTS: Our study included 181 adults with definite TSC (mean age = 33.6 years [SD = 13.7]). More than 40% (n = 75) had family members affected by TSC. Forty-six percent (n = 83) of individuals had intellectual disability. Nearly 30% (n = 52) of individuals reported living alone or with a partner/spouse. Seventy-six percent (n = 138) of people had epilepsy, 43% (n = 59) of whom had drug-resistant epilepsy, and 21% (n = 29) had undergone epilepsy surgery. Neuropsychiatric disease (n = 128) and renal angiomyolipomas (n = 130) were both present in approximately 70% of people. Renal imaging was performed in 75.7% (n = 137) of participants within the past 3 years. Renal and pulmonary function tests, as well as electrocardiograms, were recently performed in a minority of individuals. SIGNIFICANCE: Our cohort of adults with TSC showed that an important proportion have a milder phenotype, and are more frequently familial, as compared to children with TSC (and differing from prior reports in adult cohorts). Drug-resistant epilepsy, neuropsychiatric comorbidities, and renal angiomyolipoma are challenging factors in adults with TSC. Our participating medical centers generally followed recommended screening strategies, but there remain important gaps in care. Multidisciplinary and structured TSC care centers offering service to adults may help to improve the health of this important patient population.

Genome sequencing identifies rare tandem repeat expansions and copy number variants in Lennox-Gastaut syndrome.

Epilepsies are a group of common neurological disorders with a substantial genetic basis. Despite this, the molecular diagnosis of epilepsies remains challenging due to its heterogeneity. Studies utilizing whole-genome sequencing may provide additional insights into genetic causes of epilepsies of unknown aetiology. Whole-genome sequencing was used to evaluate a cohort of adults with unexplained developmental and epileptic encephalopathies (n = 30), for whom prior genetic tests, including whole-exome sequencing in some cases, were negative or inconclusive. Rare single nucleotide variants, insertions/deletions, copy number variants and tandem repeat expansions were analysed. Seven pathogenic or likely pathogenic single nucleotide variants, and two pathogenic deleterious copy number variants were identified in nine patients (32.1% of the cohort). One of the copy number variants, identified in a patient with Lennox-Gastaut syndrome, was too small to be detected by chromosomal microarray techniques. We also identified two tandem repeat expansions with clinical implications in two other patients with Lennox-Gastaut syndrome: a CGG repeat expansion in the 5'untranslated region of DIP2B, and a CTG expansion in ATXN8OS (previously implicated in spinocerebellar ataxia type 8). Three patients had KCNA2 pathogenic variants. One of them died of sudden unexpected death in epilepsy. The other two patients had, in addition to a KCNA2 variant, a second de novo variant impacting potential epilepsy-relevant genes (KCNIP4 and UBR5). Overall, whole-genome sequencing provided a genetic explanation in 32.1% of the total cohort. This is also the first report of coding and non-coding tandem repeat expansions identified in patients with Lennox-Gastaut syndrome. This study demonstrates that using whole-genome sequencing, the examination of multiple types of rare genetic variation, including those found in the non-coding region of the genome, can help resolve unexplained epilepsies.

Overcoming bashfulness: how cocaine aided Freud to summon the courage to meet Charcot.

Jean-Martin Charcot, the most celebrated neurologist of the 19th century, had a profound influence on Sigmund Freud's career. Freud spent the winter of 1885-1886 working in Charcot's neurology department in Paris. During this period, he went to Charcot's house on several occasions to participate in the very famous Tuesday soirées under the guidance of Gilles de la Tourette. Freud was always very proud to be invited and curious to meet the Parisian intellectual elite. On these occasions, however, he was very apprehensive and made frequent use of cocaine. Due to anxiety and the need to appear creative in front of Charcot, it is possible that Freud used cocaine at other times.

Overcoming bashfulness: how cocaine aided Freud to summon the courage to meet Charcot / Superando a timidez: como a cocaína ajudou Freud reunir coragem para se encontrar com Charcot

ABSTRACT Jean-Martin Charcot, the most celebrated neurologist of the 19th century, had a profound influence on Sigmund Freud's career. Freud spent the winter of 1885-1886 working in Charcot's neurology department in Paris. During this period, he went to Charcot's house on several occasions to participate in the very famous Tuesday soirées under the guidance of Gilles de la Tourette. Freud was always very proud to be invited and curious to meet the Parisian intellectual elite. On these occasions, however, he was very apprehensive and made frequent use of cocaine. Due to anxiety and the need to appear creative in front of Charcot, it is possible that Freud used cocaine at other times.

RESUMO Jean-Martin Charcot, o neurologista mais célebre do século XIX, teve uma influência profunda na carreira de Sigmund Freud. Freud visitou o Departamento de Neurologia do Hospital Salpêtrière, em Paris, chefiado pelo professor Charcot, durante o inverno de 1885-1886. Durante este período, ele foi várias vezes à casa de Charcot para participar dos famosos saraus de terça-feira, sob a orientação de GiUes de la Tourette. Nessas ocasiões, Freud ficava sempre muito orgulhoso pelo convite, curioso por encontrar a elite intelectual Parisiense, mas também muito apreensivo, e fazia uso frequente de cocaína. Devido à ansiedade e à necessidade de aparentar-se produtivo diante de Charcot, é possível que Freud tenha usado cocaína outras vezes.

Jean-Martin Charcot's influence on career of Sigmund Freud, and the influence of this meeting for the brazilian medicine / Influência de Jean-Martin Charcot na carreira de Sigmund Freud, e a influência desse encontro para a medicina brasileira

Background - Jean-Martin Charcot had a profound influence on Sigmund Freud's life and career. The founders of Brazilian neurology and psychiatry were influenced by the ideas of Charcot and Freud. Objective - To describe Charcot's influence on Freud, and both on the beginning of Brazilian Neurology and Psychiatry. Results - After Freud's stay in Charcot's neurology service during the winter of 1885-1886, there was a shift in his interest from general neurology to hysteria, hypnosis and other psychological issues, which greatly influenced the development of psychoanalytic theory. Like Charcot, Freud would become an admirer of the arts, literature, and culture. When Freud began his collection, in the late 1890s, Charcot served as an important model. In Salpêtrière Hospital, Charcot was staging a show different from modernity, capable of inspiring Freud. Antonio Austregesilo founded the first Brazilian school of Neurology, in Rio de Janeiro, inspired in Charcot. Austresegilo also practiced psychiatry, and, together Juliano Moreira and others, is considered propagator of Freud's ideas in Brazil. Conclusion - The ideas of Charcot and Freud were fundamental in the formation of physicians who helped to found and to consolidate the Brazilian neurology and psychiatry.(AU)

Introdução - Jean-Martin Charcot exerceu uma profunda influência na vida e na carreira de Sigmund Freud. Os fundadores da neurologia e da psiquiatria brasileiras foram influenciados pelas ideias de Charcot e de Freud. Objetivo - Descrever a influência de Charcot sobre Freud e de ambos sobre o início da Neurologia e da Psiquiatria brasileiras. Resultados - Após a permanência de Freud no serviço de neurologia de Charcot durante o inverno de 1885-1886, houve uma mudança em seu interesse da neurologia geral para histeria, hipnose e outras questões psicológicas, o que influenciou muito o desenvolvimento da teoria psicanalítica. Como Charcot, Freud se tornaria admirador das artes, literatura e cultura. Quando Freud começou sua coleção, no final da década de 1890, Charcot serviu de modelo importante. No Hospital Salpêtrière, Charcot era a representação da modernidade, capaz de inspirar Freud. Antonio Austregésilo fundou a primeira escola brasileira de Neurologia, no Rio de Janeiro, inspirada em Charcot. Austresegilo também praticou psiquiatria, e, juntamente com Juliano Moreira e outros, é considerado propagador das ideias de Freud no Brasil.Conclusão - As ideias de Charcot e Freud foram fundamentais na formação de médicos que ajudaram a fundar e consolidar a neurologia e a psiquiatria brasileiras.(AU)