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- Antonsson, Malin, 1986, et al.
(författare)
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Post-surgical effects on language in patients with presumed low-grade glioma
- 2018
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314. ; 137:5, s. 469-480
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Low-grade glioma (LGG) is a slow-growing brain tumour often situated in or near areas involved in language and/or cognitive functions. Thus, language impairments due to tumour growth or surgical resection are obvious risks. We aimed to investigate language outcome following surgery in patients with presumed LGG, using a comprehensive and sensitive language assessment. Materials and methods: Thirty-two consecutive patients with presumed LGG were assessed preoperative, early post-operative, and 3 months post-operative using sensitive tests including lexical retrieval, language comprehension and high-level language. The patients’ preoperative language ability was compared with a reference group, but also with performance at post-operative controls. Further, the association between tumour location and language performance pre-and post-operatively was explored. Results: Before surgery, the patients with presumed LGG performed worse on tests of lexical retrieval when compared to a reference group (BNT: LGG-group median 52, Reference-group median 54, P = .002; Animals: LGG-group mean 21.0, Reference-group mean 25, P = 001; Verbs: LGG-group mean 17.3, Reference-group mean 21.4, P = .001). At early post-operative assessment, we observed a decline in all language tests, whereas at 3 months there was only a decline on a single test of lexical retrieval (Animals: preoperative. median 20, post-op median 14, P = .001). The highest proportion of language impairment was found in the group with a tumour in language-eloquent areas at all time-points. Conclusions: Although many patients with a tumour in the left hemisphere deteriorated in their language function directly after surgery, their prognosis for recovery was good.
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| 2. |
- Antonsson, Malin, 1986, et al.
(författare)
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Pre-operative language ability in patients with presumed low-grade glioma
- 2018
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Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 137:1, s. 93-102
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Tidskriftsartikel (refereegranskat)abstract
- In patients with low-grade glioma (LGG), language deficits are usually only found and investigated after surgery. Deficits may be present before surgery but to date, studies have yielded varying results regarding the extent of this problem and in what language domains deficits may occur. This study therefore aims to explore the language ability of patients who have recently received a presumptive diagnosis of low-grade glioma, and also to see whether they reported any changes in their language ability before receiving treatment. Twenty-three patients were tested using a comprehensive test battery that consisted of standard aphasia tests and tests of lexical retrieval and high-level language functions. The patients were also asked whether they had noticed any change in their use of language or ability to communicate. The test scores were compared to a matched reference group and to clinical norms. The presumed LGG group performed significantly worse than the reference group on two tests of lexical retrieval. Since five patients after surgery were discovered to have a high-grade glioma, a separate analysis excluding them were performed. These analyses revealed comparable results; however one test of word fluency was no longer significant. Individually, the majority exhibited normal or nearly normal language ability and only a few reported subjective changes in language or ability to communicate. This study shows that patients who have been diagnosed with LGG generally show mild or no language deficits on either objective or subjective assessment.
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| 3. |
- Danielsson, Anna, 1973, et al.
(författare)
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MethPed: a DNA methylation classifier tool for the identification of pediatric brain tumor subtypes
- 2015
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Ingår i: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7083 .- 1868-7075. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Classification of pediatric tumors into biologically defined subtypes is challenging, and multifaceted approaches are needed. For this aim, we developed a diagnostic classifier based on DNA methylation profiles. Results: Methylation data generated by the Illumina Infinium HumanMethylation 450 BeadChip arrays were downloaded from the Gene Expression Omnibus (n = 472). Using the data, we built MethPed, which is a multiclass random forest algorithm, based on DNA methylation profiles from nine subgroups of pediatric brain tumors. DNA from 18 regional samples was used to validate MethPed. MethPed was additionally applied to a set of 28 publically available tumors with the heterogeneous diagnosis PNET. MethPed could successfully separate individual histology tumor types at a very high accuracy (kappa = 0.98). Analysis of a regional cohort demonstrated the clinical benefit of MethPed, as confirmation of diagnosis of tumors with clear histology but also identified possible differential diagnoses in tumors with complicated and mixed type morphology. Conclusions: We demonstrate the utility of methylation profiling of pediatric brain tumors and offer MethPed as an easy-to-use toolbox that allows researchers and clinical diagnosticians to test single samples as well as large cohorts for subclass prediction of pediatric brain tumors. This will immediately aid clinical practice and importantly increase our molecular knowledge of these tumors for further therapeutic development.
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| 4. |
- Deland, Lily, et al.
(författare)
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Novel TPR::ROS1 Fusion Gene Activates MAPK, PI3K and JAK/STAT Signaling in an Infant-type Pediatric Glioma.
- 2022
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Ingår i: Cancer genomics & proteomics. - : Anticancer Research USA Inc.. - 1109-6535 .- 1790-6245. ; 19:6, s. 711-726
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Tidskriftsartikel (refereegranskat)abstract
- Although fusion genes involving the proto-oncogene receptor tyrosine kinase ROS1 are rare in pediatric glioma, targeted therapies with small inhibitors are increasingly being approved for histology-agnostic fusion-positive solid tumors.Here, we present a 16-month-old boy, with a brain tumor in the third ventricle. The patient underwent complete resection but relapsed two years after diagnosis and underwent a second operation. The tumor was initially classified as a low-grade glioma (WHO grade 2); however, methylation profiling suggested the newly WHO-recognized type: infant-type hemispheric glioma. To further refine the molecular background, and search for druggable targets, whole genome (WGS) and whole transcriptome (RNA-Seq) sequencing was performed.Concomitant WGS and RNA-Seq analysis revealed several segmental gains and losses resulting in complex structural rearrangements and fusion genes. Among the top-candidates was a novel TPR::ROS1 fusion, for which only the 3' end of ROS1 was expressed in tumor tissue, indicating that wild type ROS1 is not normally expressed in the tissue of origin. Functional analysis by Western blot on protein lysates from transiently transfected HEK293 cells showed the TPR::ROS1 fusion gene to activate the MAPK-, PI3K- and JAK/STAT- pathways through increased phosphorylation of ERK, AKT, STAT and S6. The downstream pathway activation was also confirmed by immunohistochemistry on tumor tissue slides from the patient.We have mapped the activated oncogenic pathways of a novel ROS1-fusion gene and broadened the knowledge of the newly recognized infant-type glioma subtype. The finding facilitates suitable targeted therapies for the patient in case of relapse.
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| 7. |
- Wenger, Anna, 1990, et al.
(författare)
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Stem cell cultures derived from pediatric brain tumors accurately model the originating tumors.
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8, s. 18626-18639
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Tidskriftsartikel (refereegranskat)abstract
- Brain tumors are the leading cause of cancer-related death in children but high-grade gliomas in children and adolescents have remained a relatively under-investigated disease despite this. A better understanding of the cellular and molecular pathogenesis of the diseases is required in order to improve the outcome for these children. In vitro-cultured primary tumor cells from patients are indispensable tools for this purpose by enabling functional analyses and development of new therapies. However, relevant well-characterized in vitro cultures from pediatric gliomas cultured under serum-free conditions have been lacking. We have therefore established patient-derived in vitro cultures and performed thorough characterization of the cells using large-scale analyses of DNA methylation, copy-number alterations and investigated their stability during prolonged time in culture. We show that the cells were stable during prolonged culture in serum-free stem cell media without apparent alterations in morphology or growth rate. The cells were proliferative, positive for stem cell markers, able to respond to differentiation cues and initiated tumors in zebrafish and mice suggesting that the cells are cancer stem cells or progenitor cells. The cells accurately mirrored the tumor they were derived from in terms of methylation pattern, copy number alterations and DNA mutations. These unique primary in vitro cultures can thus be used as a relevant and robust model system for functional studies on pediatric brain tumors.
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| 8. |
- Almotairi, Fawaz, et al.
(författare)
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Acute deterioration of adults with Chiari I malformation associated with extensive syrinx
- 2020
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Ingår i: British Journal of Neurosurgery. - : Informa UK Limited. - 0268-8697 .- 1360-046X. ; 34:1, s. 13-17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chiari I malformation (CMI) is usually a chronic disorder, although it may also present as a life-threatening condition with need for urgent decompression. Studies of acute deterioration of CMI are scarce. The identification of preoperative radiological factors that predict acute deterioration in adult patients with CMI facilitates planning of early decompression and decreases CMI-related morbidity. Patients and methods: This is a retrospective study of all adult patients with CMI who were referred to Sahlgrenska University Hospital, Sweden and underwent occipitocervical decompression in the period 2006-2016. In total, 65 consecutive patients were included and data regarding the preoperative degree of tonsillar herniation and syrinx (size, length and degree of rostral extension) were registered. Acute deterioration and the need for urgent surgical decompression within 24 h of hospitalisation were noted. Results: Three patients presented with acute deterioration of symptoms (4.6%) and showed an increased length and size of syrinx and more rostral extension of syrinx as compared to non-acute patients with CMI. Conclusion: Our study highlights the incidence of acute deterioration of CMI and shows the importance of assessing preoperative size, length and rostral extension of CMI-associated syrinx as indicators of acute deterioration so that CMI patients can be assigned to early surgical decompression.
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| 9. |
- Almotairi, Fawaz, et al.
(författare)
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Cerebrospinal fluid disturbance in overweight women after occipitocervical decompression in Chiari malformation type I
- 2016
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Ingår i: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 158:3, s. 589-594
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid disturbance (CSFD) is a well-known complication after occipitocervical decompression (OCD) in patients with Chiari malformation type I (CMI). There is scarce data focusing on preoperative patients' factors predisposing to development of CSF disturbance. The aim of this study is to evaluate a prognostic value of some patients' factors in the prediction of CSFD after OCD in CMI patients. We undertook a 10-year (2003-2013) retrospective study of all OCD in patients with CMI performed at Sahlgrenska IC, Sahlgrenska University Hospital, Sweden. A total of 52 consecutive patients were obtained from the operation database and we excluded one patient who was previously diagnosed with normal-pressure hydrocephalus. Data regarding preoperative age, body mass index, gender, degree of tonsillar herniation and syrinx were registered. Development of CSFD after OCD was noted. Of the 51 patients reviewed, six had CSFD after OCD and were managed using a form of CSF diversion procedure. All of the patients who developed CSFD were females. They had a mean body mass index of 32.3 compared to a mean of 24.3 in patients without CSFD (p = 0.0011). There was no difference between the two groups with regard to the other examined patient factors. CSF diversion was needed in six consecutive adult Chiari malformation type I patients who underwent occipitocervical decompression. All patients with postoperative CSFD were female and their mean BMI was significantly higher than patients without this complication.
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| 10. |
- Almotairi, Fawaz, et al.
(författare)
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Chiari I malformation—neuropsychological functions and quality of life
- 2020
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Ingår i: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 162:7, s. 1575-1582
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the neuropsychological (NP) functioning and quality of life (QOL) before and 3months after surgery on adults with Chiari I malformation (CMI). Patients and methods: All adult patients who had been diagnosed with CMI were invited to participate. Those who participated were assessed using a Hospital Anxiety and Depression scale (HAD) and NP examinations. Their QOL was assessed using the self-reported life satisfaction checklist, LiSat-11 and the five-dimensional EuroQol measurement of health outcome, EQ-5D-5L. All assessments were carried out both before and 3months after surgery was performed. Demographic data and comorbidities were also registered. Results: Of the 11 patients who underwent NP assessment, the majority demonstrated cognitive functioning within the normal range. However, postoperatively, their performance in verbal learning, psychomotor speed, colour naming speed and the ability to manage interference through response selection and inhibition (aspects of executive functioning) was significantly improved. Thirteen patients completed QOL assessments. When LiSat-11 item domains were compared with those of healthy subjects, patients reported a lower level of satisfaction with their life quality both before and after surgery. However, the EQ-5D-5L measurements, i.e., the descriptive system and the visual analogue, indicated that their QOL of life was significantly improved after surgery. Conclusion: There is scarcely any literature documenting effects of surgery on the QOL of CMI patients. The study we present here breaks new ground by comparing pre- and postoperative NP functions in CMI. We also examine the value of surgery for improving both NP functions and QOL in CMI. © 2019, Springer-Verlag GmbH Austria, part of Springer Nature.
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