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Impact d’une tumeur de la fosse postérieure sur le développement intellectuel et mnésique de l’enfant

Abstract : Pediatric posterior fossa tumors (PFT) account for two-thirds of all pediatric brain tumors. The most common malignant PFT is medulloblastoma (40%), followed by ependymoma (10%). Surgery, radiotherapy and/or chemotherapy are the current therapeutic approaches. As a result of the progress of treatment, event-free survival has significantly improved. Unfortunately, these children suffer from many cognitive impairments partly attributed to radiotherapy, especially in young children. Alleviating neurocognitive impairments has become one of the major challenges of pediatric oncology. Using an approach combining neuroimaging and neuropsychology, this work examines the relationship between treatments and neuropsychological performances as a function of age in children treated for PFT. The experimental contribution is based on two main axes. The first axis uses an exploratory approach to investigate the relationship between the decline of intellectual functioning and radiation dose distribution. For this purpose, we analyze, with a whole brain analysis, the relation between regional biological dose and changes over time of different cognitive scores (IQ, processing speed and working memory). Our results suggest a positive association between working memory decline and high dose (Equivalent Uniform Dose, EUD) delivered to the orbitofrontal regions, whereas decline of processing speed seems more related to EUD in the temporal lobes and posterior fossa. The 2nd axis uses a hypothesis-driven approach to determine the susceptibility of episodic memory (EM) impairment and hippocampal alteration in young child PFT patients (2-13yo). This part is structured around two aims: First, the assessment of PFT EM performances, thanks to an EM task, in comparison to Controls; second, the exploration of longitudinal patterns of hippocampal volume as a potential neural substrate underlying EM performance. The main results support the evidence of EM impairment in the PFT condition, which varied according to age: in the younger patients (<7yo) impairment was global while in the older it involved only the long term recognition of temporal details (i.e. ‘When’). However, at this stage of the work, several methodological difficulties mainly related to the registration parameters of the segmentation algorithm prevent us from achieving hippocampal volume analysis. This work brings new knowledge about the role of some risk factors on specific cognitive difficulties. Preventing long-term impairments of these children remains a challenge for years to come.
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Submitted on : Thursday, April 25, 2019 - 5:08:33 PM
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Élodie Doger de Spéville. Impact d’une tumeur de la fosse postérieure sur le développement intellectuel et mnésique de l’enfant. Neurosciences [q-bio.NC]. Université Sorbonne Paris Cité, 2017. Français. ⟨NNT : 2017USPCB017⟩. ⟨tel-02111027⟩

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