Tumours in the pineal region in the paediatric age: Reports of 23 cases and a review of the literature

Introducción. Los tumores de la región pineal se localizan en una encrucijada de estructuras neurovasculares de difícil acceso quirúrgico y limitadas posibilidades de resección; por ello, el manejo de estas lesiones habitualmente requiere la asociación de tratamiento adyuvante radioterápico y/o quimioterápico. Pacientes y métodos. Análisis retrospectivo de las características epidemiológicas, clínicas, neurorradiológicas y anatomopatológicas de 23 pacientes con tumores de la región pineal tratados entre los años 1997 y 2010 en el Hospital Infantil Niño Jesús. Se discuten los factores implicados en el pronóstico de esta cohorte tras el tratamiento quirúrgico o adyuvante. Resultados. El estudio incluyó 6 niñas y 17 niños con edades comprendidas entre los 4 meses y 18 años. El 95% de los pacientes comenzó con signos de hidrocefalia aguda o subaguda, que precisaron la implantación de una derivación ventriculoperitoneal (82%). Se obtuvo una muestra histológica tumoral en todos los casos. Cinco pacientes fueron biopsiados y 18 fueron intervenidos mediante craneotomía. El germinoma (ocho casos) y el teratoma maduro (un caso) fueron los tumores con mayor supervivencia; los tumores no germinomatosos (tres casos), del parénquima pineal (cuatro casos) y gliomas (cinco casos) presentaron mayor tasa de recidiva y un peor pronóstico. Conclusión. El estudio de marcadores tumorales permite orientar el diagnóstico de determinados tumores de la región pineal. Actualmente, se recomienda realizar una toma histológica tumoral para establecer un diagnóstico preciso y un tratamiento oncológico específicoIntroduction. Tumours in the pineal region are located at a meeting point of several neurovascular structures that are difficult to reach surgically and for which the possibility of resection is limited; as a result the management of these lesions usually requires associated adjunctive treatment with radiotherapy and/or chemotherapy. Patients and methods. This study is a retrospective analysis of the epidemiological, clinical, neuroimaging and pathological characteristics of 23 patients with tumours in the pineal region who were treated between the years 1997 and 2010 in the Hospital Infantil Niño Jesús. The factors involved in the prognosis of this cohort following surgical or adjunctive treatment are also discussed. Results. Subjects included in the study were 6 girls and 17 boys with ages ranging from 4 months to 18 years. It was found that the initial symptoms in 95% of the patients were signs of acute or subacute hydrocephalus, which required the placement of a ventriculoperitoneal shunt (82%). A histological sample of the tumour tissue was collected in all cases. Biopsy samples were taken in the case of five patients and 18 underwent surgery involving a craniotomy. Germinoma (eight cases) and mature teratoma (one case) were the tumours with the longest survival times; non-germinomatous tumours (three cases), those of the pineal parenchyma (four cases) and gliomas (five cases) presented the highest rates of recurrence and a poorer prognosis. Conclusions. The study of tumour markers can be used to guide the diagnosis of certain tumours of the pineal region. At present, the recommended procedure involves taking a histological sample of the tumour in order to establish an accurate diagnosis and a specific oncological treatmen

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease