RESUMO
Congenital disorders of glycosylation are a continuously expanding group of monogenic disorders of glycoprotein and glycolipid glycan biosynthesis. These disorders mostly manifest with multisystem involvement. Individuals with ALG8-CDG commonly present with hypotonia, protein-losing enteropathy, and hepatic involvement. Here, we describe seven unreported individuals diagnosed with ALG8-CDG based on biochemical and molecular testing and we identify nine novel variants in ALG8, bringing the total to 26 individuals with ALG8-CDG in the medical literature. In addition to the typical multisystem involvement documented in ALG8-CDG, our cohort includes the two oldest patients reported and further expands the phenotype of ALG8-CDG to include stable intellectual disability, autism spectrum disorder and other neuropsychiatric symptoms. We further expand the clinical features in a variety of organ systems including ocular, musculoskeletal, dermatologic, endocrine, and cardiac abnormalities and suggest a comprehensive evaluation and monitoring strategy to improve clinical management.
Assuntos
Transtorno do Espectro Autista , Defeitos Congênitos da Glicosilação , Defeitos Congênitos da Glicosilação/diagnóstico , Defeitos Congênitos da Glicosilação/genética , Defeitos Congênitos da Glicosilação/terapia , Glucosiltransferases/genética , Glicosilação , Humanos , FenótipoRESUMO
INTRODUCTION: Recently, an additional trigeminothalamic tract - the dorsal trigeminothalamic tract - has been described in human brainstems by our group next to the known ventral trigeminothalamic tract. As various elements of the trigeminal system are known to be organised in a somatotopic fashion, the question arose whether the fibres within the trigeminal root show specific distributions patterns in their contribution to the ventral trigeminothalamic tract and dorsal trigeminothalamic tract specifically. METHODS: This study investigated the arrangement of the fibres in the trigeminal root by combining various imaging methods in the pons of 11 post-mortem specimens. The pons were investigated by polarised light imaging (PLI) (n = 4; to quantify fibre orientation; 100 µm interslice distance), histochemical staining methods (n = 3; to visualise the internal myeloarchitecture; 60 µm) and ultra-high field, post-mortem magnetic resonance imaging (MRI) (n = 4; for tractography; 500 µm interslice distance). RESULTS: This study shows that the fibres, from the point where the trigeminal root enters the brainstem, are distinctly arranged by their contribution to the ventral trigeminothalamic tract and dorsal trigeminothalamic tract. This finding is supported by both post-mortem, ultra-high dMRI and different light microscopy techniques. CONCLUSION: The data from this study suggest that the fibres in the superior half of the root contribute mainly to the ventral trigeminothalamic tract, whereas the fibres in the inferior half mainly contribute to the dorsal trigeminothalamic tract. Such a somatotopic organisation could possibly create new insights into the anatomical origin of trigeminal neuralgia and the clinical relevance of this somatotopic organisation should therefore be further explored.
Assuntos
Ponte , Tronco Encefálico/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Ponte/diagnóstico por imagem , Nervo Trigêmeo/diagnóstico por imagem , Neuralgia do TrigêmeoRESUMO
OBJECTIVE: The primary objective of this anatomical study was to apply innovative imaging techniques to increase understanding of the microanatomical structures of the brainstem related to safe entry zones. The authors hypothesized that such a high-detail overview would enhance neurosurgeons' abilities to approach and define anatomical safe entry zones for use with microsurgical resection techniques for intrinsic brainstem lesions. METHODS: The brainstems of 13 cadavers were studied with polarized light imaging (PLI) and 11.7-T MRI. The brainstem was divided into 3 compartments-mesencephalon, pons, and medulla-for evaluation with MRI. Tissue was further sectioned to 100 µm with a microtome. MATLAB was used for further data processing. Segmentation of the internal structures of the brainstem was performed with the BigBrain database. RESULTS: Thirteen entry zones were reported and assessed for their safety, including the anterior mesencephalic zone, lateral mesencephalic sulcus, interpeduncular zone, intercollicular region, supratrigeminal zone, peritrigeminal zone, lateral pontine zone, median sulcus, infracollicular zone, supracollicular zone, olivary zone, lateral medullary zone, and anterolateral sulcus. The microanatomy, safety, and approaches are discussed. CONCLUSIONS: PLI and 11.7-T MRI data show that a neurosurgeon possibly does not need to consider the microanatomical structures that would not be visible on conventional MRI and tractography when entering the mentioned safe entry zones. However, the detailed anatomical images may help neurosurgeons increase their understanding of the internal architecture of the human brainstem, which in turn could lead to safer neurosurgical intervention.
RESUMO
BACKGROUND: Laser interstitial thermal therapy (LITT) is a minimal invasive neurosurgical technique for the treatment of brain tumors. Results of LITT have been reported in a case series of patients with deep seated and/or recurrent glioblastoma or cerebral metastases. With this review we aim to summarize the currently available evidence regarding safety and effectiveness of LITT in patients with newly diagnosed glioblastoma (nGBM). METHODS: A literature search was performed using electronic databases (PubMed and Embase). Papers were assessed for the methodological quality using the Risk Of Bias In Non- randomised Studies - of Interventions (ROBINS-I) tool, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the quality of the evidence. RESULTS: We identified 835 papers of which only 11 articles were eligible for our review. All papers suffered from serious or critical risk of bias, and the quality of evidence was graded as very low according to the GRADE criteria. None of the studies was randomized and reporting of confounders and other parameters was poor. Median overall survival (OS) ranged from 4.1 to 32 months and progression free survival (PFS) from 2 to 31 months. The mean complication rate was 33.7%. No quality of life or cost-effectiveness data were reported. CONCLUSIONS: Due to the low quality of the studies, it is not possible to draw firm conclusions regarding the (cost) effectiveness of LITT in patients with newly diagnosed glioblastoma. The low quality of evidence shows the need for a well-designed prospective multicenter randomized controlled trial.