| 1. |
- 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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Discovery of a rare GKAP1-NTRK2 fusion in a pediatric low-grade glioma, leading to targeted treatment with TRK-inhibitor larotrectinib
- 2021
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Ingår i: Cancer Biology & Therapy. - : Taylor & Francis. - 1538-4047 .- 1555-8576. ; 22:3, s. 184-195
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Tidskriftsartikel (refereegranskat)abstract
- Here we report a case of an 11-year-old girl with an inoperable tumor in the optic chiasm/hypothalamus, who experienced several tumor progressions despite three lines of chemotherapy treatment. Routine clinical examination classified the tumor as a BRAF-negative pilocytic astrocytoma. Copy-number variation profiling of fresh frozen tumor material identified two duplications in 9q21.32–33 leading to breakpoints within the GKAP1 and NTRK2 genes. RT-PCR Sanger sequencing revealed a GKAP1-NTRK2 exon 10–16 in-frame fusion, generating a putative fusion protein of 658 amino acids with a retained tyrosine kinase (TK) domain. Functional analysis by transient transfection of HEK293 cells showed the GKAP1-NTRK2 fusion protein to be activated through phosphorylation of the TK domain (Tyr705). Subsequently, downstream mediators of the MAPK- and PI3K-signaling pathways were upregulated in GKAP1-NTRK2 cells compared to NTRK2 wild-type; phosphorylated (p)ERK (3.6-fold), pAKT (1.8- fold), and pS6 ribosomal protein (1.4-fold). Following these findings, the patient was enrolled in a clinical trial and treated with the specific TRK-inhibitor larotrectinib, resulting in the arrest of tumor growth. The patient’s condition is currently stable and the quality of life has improved significantly. Our findings highlight the value of comprehensive clinical molecular screening of BRAF-negative pediatric low-grade gliomas, to reveal rare fusions serving as targets for precision therapy.
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| 5. |
- 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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| 6. |
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| 7. |
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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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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| 11. |
- 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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| 12. |
- Almotairi, Fawaz, et al.
(författare)
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Swallowing Dysfunction in Adult Patients with Chiari I Malformation
- 2018
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Ingår i: Journal of Neurological Surgery Part B-Skull Base. - : Georg Thieme Verlag KG. - 2193-6331 .- 2193-634X. ; 79:6, s. 606-613
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Tidskriftsartikel (refereegranskat)abstract
- Background Swallowing difficulties have been reported in patients with Chiari I malformation (CMI) with a prevalence of 4 to 47%, but existing evidence is based only on case reports. We aimed to prospectively study swallowing function in adult patients with CMI before and 3 months after surgical decompression. Methods We included all adult patients diagnosed with CMI from September 2015 to October 2017 who underwent a planned surgery at Sahlgrenska University Hospital, Sweden. The patients were offered the opportunity to participate in and undergo an assessment consisting of the "Watson Dysphagia Scale (WDS)" and "EORTC QLQ-OG25" written questionnaires in addition to videofluoroscopic examination of swallowing (VFS) before and 3 months after surgery. Demographic data and comorbidities were recorded. Results Eleven patients were included, nine of which underwent both pre- and postoperative evaluations. Four patients (36%) reported varying degrees of swallowing complaints (meanWDS score, 16). In two of these, there was substantial penetration of contrast material into the laryngeal vestibule on VFS, and in the other two patients, minor swallowing disturbances were observed. Borderline deviations from normal VFS findings were also found in three asymptomatic patients. Although not all VFS deviations completely disappeared after surgery, the patients reported no remaining symptoms. Conclusion Symptoms of dysphagia and objective abnormalities on VFS are not uncommon in CMI patients. Surgery has the potential to remedy underlying causes of dysphagia, thereby relieving its symptoms. OULEZZ AO, 1985, JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY, V9, P1033
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| 13. |
- Andrén, Kerstin, 1980, et al.
(författare)
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Natural course of idiopathic normal pressure hydrocephalus
- 2014
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050. ; 2014:85, s. 806-810
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objectives The natural course of idiopathic normal pressure hydrocephalus (iNPH) has not been thoroughly studied. The consequences of postponing shunt treatment are largely unknown. We aimed to describe the effects of waiting for more than 6months before surgery and to compare the outcome with that seen in patients who waited for less than 3months. Methods 33 patients (iNPHDelayed) underwent an initial investigation (Pre-op 1), followed by re-examination, just prior to surgery, after waiting for at least 6months (Pre-op 2). Outcome was evaluated after 3months of treatment. 69 patients who were surgically treated within 3months after Pre-op 1 and who were also evaluated after 3months of treatment constituted a comparison group (iNPHEarly). Evaluations were done with the iNPH scale and the modified Rankin Scale (mRS). iNPHDelayed patients were prospectively studied with regard to outcome, whereas the comparison group iNPHEarly was defined and analysed retrospectively. Results iNPHDelayed patients deteriorated significantly during their wait for surgery, with progression of symptom severity ranging from +7 to −47 on the iNPH scale, and from 0 to +3 on the mRS (both p<0.001). The magnitude of change after surgery was similar in the groups, but since the symptoms of iNPHDelayed patients had worsened while waiting, their final outcome was significantly poorer. Conclusions The natural course of iNPH is symptom progression over time, with worsening in gait, balance and cognitive symptoms. This deterioration is only partially reversible. To maximise the benefits of shunt treatment, surgery should be performed soon after diagnosis.
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| 14. |
- Bartley, Andreas, et al.
(författare)
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Effect of Irrigation Fluid Temperature on Recurrence in the Evacuation of Chronic Subdural Hematoma A Randomized Clinical Trial
- 2023
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Ingår i: Jama Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157.
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Tidskriftsartikel (refereegranskat)abstract
- ImportanceThe effect of a physical property of irrigation fluid (at body vs room temperature) on recurrence rate in the evacuation of chronic subdural hematoma (cSDH) needs further study.ObjectiveTo explore whether irrigation fluid temperature has an influence on cSDH recurrence.Design, Setting, and ParticipantsThis was a multicenter randomized clinical trial performed between March 16, 2016, and May 30, 2020. The follow-up period was 6 months. The study was conducted at 3 neurosurgical departments in Sweden. All patients older than 18 years undergoing cSDH evacuation during the study period were screened for eligibility in the study.InterventionsThe study participants were randomly assigned by 1:1 block randomization to the cSDH evacuation procedure with irrigation fluid at room temperature (RT group) or at body temperature (BT group).Main Outcomes and MeasuresThe primary end point was recurrence requiring reoperation within 6 months. Secondary end points were mortality, health-related quality of life, and complication frequency.ResultsAt 6 months after surgery, 541 patients (mean [SD] age, 75.8 [9.8] years; 395 men [73%]) had a complete follow-up according to protocol. There were 39 of 277 recurrences (14%) requiring reoperation in the RT group, compared with 16 of 264 recurrences (6%) in the BT group (odds ratio, 2.56; 95% CI, 1.38-4.66; P < .001). There were no significant differences in mortality, health-related quality of life, or complication frequency.Conclusions and RelevanceIn this study, irrigation at body temperature was superior to irrigation at room temperature in terms of fewer recurrences. This is a simple, safe, and readily available technique to optimize outcome in patients with cSDH. When irrigation is used in cSDH surgery, irrigation fluid at body temperature should be considered standard of care.
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| 15. |
- Bartley, Andreas, et al.
(författare)
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Is a drainage time of less than 24 h sufficient after chronic subdural hematoma evacuation?
- 2023
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Ingår i: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 165, s. 711-715
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIt is well established that the use of a postoperative drain after chronic subdural hematoma surgery reduces recurrence rates, and it is common to use a postoperative drain for longer than 24 h. It is unclear whether this is superior to a shorter drainage time of less than 24 h. Our aim was to compare a postoperative drainage longer or shorter than 24 h after chronic subdural hematoma evacuation.Materials and methodsIn this retrospective single centre study, 207 adult patients undergoing chronic subdural hematoma evacuation with a postoperative drainage longer (LDT-group) or shorter (SDT-group) than 24 h were compared regarding recurrence, mortality within 6 months and complications requiring hospital admission within 30 days. Length of hospital stay was also recorded. An active subgaleal drain was used. In addition to the retrospective cohort, we also studied the total volume drained per hour after cSDH surgery in a prospective cohort of 10 patients.ResultsRecurrence occurred in 12/96 (12.5%) in the LDT-group and in 13/111 (11.7%) patients in the SDT-group (p = 0.15). There was no significant difference between groups regarding recurrence, complications or mortality. The prospective cohort showed that most of the drainage occurred within the first hours after surgery.ConclusionOur data show that a postoperative drainage duration of less than 24 h does not lead to an increase in recurrence, complications or mortality compared to a drainage time of more than 24 h. A shorter drainage duration (< 24 h) after cSDH surgery facilitated earlier mobilisation and shorter hospital stay.
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| 16. |
- Bartley, Andreas, et al.
(författare)
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The influence of irrigation fluid temperature on recurrence in the evacuation of chronic subdural hematoma.
- 2020
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Ingår i: Acta neurochirurgica. - : Springer Science and Business Media LLC. - 0942-0940 .- 0001-6268. ; 162, s. 485-488
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Tidskriftsartikel (refereegranskat)abstract
- Chronic subdural hematomas (cSDH) are one of the most common conditions requiring neurosurgical treatment. The reported recurrence after surgery is 3-21.5% with closed system drainage. In clinical practice, irrigation fluids at body temperature (37°C) and at room temperature (22°C) are routinely used in the evacuation of cSDH. Our hypothesis was that irrigation at body temperature might have more beneficial effects on coagulation and solubility of the chronic subdural hematoma than irrigation at room temperature. The aim of this study was to compare the effects of different intraoperative irrigation fluid temperatures on recurrence rates.This was a retrospective study where we included all consecutive patients from a defined geographical area of western Sweden between September 2013 and November 2014. In the course of 6months, we performed intraoperative irrigation at body temperature (37°C, BT-group) during burr hole evacuation of chronic subdural hematoma. This was then compared with the previous 6-month period, when irrigation fluid at room temperature (22°C, RT-group) was used. The primary endpoint was same-sided recurrence in need of reoperation within 6months.Recurrence occurred in 11 of 84 (13.1%) patients in the RT-group compared with 4 of 88 (4.5%) in the BT-group (p=0.013). There were no significant between-group differences regarding age, sex, duration of surgery, frequency of bilateral hematomas, hematoma density, and use of anticoagulant/antithrombotic therapy.Our study demonstrates that intraoperative irrigation fluid at body temperature is associated with lower recurrence rates compared with irrigation fluid at room temperature. To investigate this further, a prospective randomized controlled trial has been initiated (clinicaltrials.gov, NCT0275235).ClinicalTrials.gov Identifier: NCT0275235.
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| 17. |
- Bartley, Andreas, et al.
(författare)
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The Swedish study of Irrigation-fluid temperature in the evacuation of Chronic subdural hematoma (SIC!) : study protocol for a multicenter randomized controlled trial
- 2017
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Ingår i: Trials. - : BIOMED CENTRAL LTD. - 1745-6215. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic subdural hematoma (cSDH) is one of the most common conditions encountered in neurosurgical practice. Recurrence, observed in 5-30% of patients, is a major clinical problem. The temperature of the irrigation fluid used during evacuation of the hematoma might theoretically influence recurrence rates since irrigation fluid at body temperature (37 degrees C) may beneficially influence coagulation and cSDH solubility when compared to irrigation fluid at room temperature. Should no difference in recurrence rates be observed when comparing irrigation-fluid temperatures, there is no need for warmed fluids during surgery. Our main aim is to investigate the effect of irrigation-fluid temperature on recurrence rates and clinical outcomes after cSDH evacuation using a multicenter randomized controlled trial design.Methods: The study will be conducted in three neurosurgical departments with population-based catchment areas using a similar surgical strategy. In total, 600 patients fulfilling the inclusion criteria will randomly be assigned to either intraoperative irrigation with fluid at body temperature or room temperature. The power calculation is based on a retrospective study performed at our department showing a recurrence rate of 5% versus 12% when comparing irrigation fluid at body temperature versus fluid at room temperature (unpublished data). The primary endpoint is recurrence rate of cSDH analyzed at 6 months post treatment. Secondary endpoints are mortality rate, complications and health-related quality of life.Discussion: Irrigation-fluid temperature might influence recurrence rates in the evacuation of chronic subdural hematomas. We present a study protocol for a multicenter randomized controlled trial investigating our hypothesis that irrigation fluid at body temperature is superior to room temperature in reducing recurrence rates following evacuation of cSDH.
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| 18. |
- Corell, Alba, et al.
(författare)
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Successful adaptation of twinning concept for global neurosurgery collaborations-a validation study
- 2024
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Ingår i: ACTA NEUROCHIRURGICA. - : Springer. - 0001-6268 .- 0942-0940. ; 166:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Globally, many regions have an urgent, unmet need of neurosurgical care. A multi-step neurosurgical twinning technique, International Neurosurgical Twinning Modeled for Africa (INTIMA), was proved to be successful during a previous mission to Neurosurgical Unit, Enugu, Nigeria. The Swedish African Neurosurgical Collaboration (SANC) performed a developmental mission together with the local neurosurgical unit in The Gambia, adopting the INTIMA model.Methods A multidisciplinary team visited for a 2-week collaborative mission at the Neurosurgical Department of the Edward Francis Small Teaching Hospital in Banjul, The Gambia. The mission followed the data of neurosurgical operations during and after the mission as well as about the operations 3 months prior to and after the mission was collected.Results During the mission, a total of 22 operations was carried out, the most common being degenerative spinal conditions (n = 9). In the 3 months following the mission, 43 operations were performed compared to 24 during the 3 months leading up to the mission. The complexity of the performed procedures increased after the mission. An operating microscope (Moller-Wedel) was donated and installed and the neurosurgeons on site underwent training in microneurosurgery. The surgical nurses, nurses at the postoperative ward, and the physiotherapists underwent training. A biomedical engineer serviced multiple appliances and devices improving the patient care on site while training local technicians.Conclusion This study validated the use of the INTIMA model previously described in a mission by Swedish African Neurosurgical Collaboration (SANC). The model is sustainable and produces notable results. The core strength of the model is in the multidisciplinary team securing all the aspects and steps of the neurosurgical care. Installation of an operating microscope opened for further microsurgical possibilities, improving the neurosurgical care in The Gambia.
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| 19. |
- Danielsson, Anna, 1973, et al.
(författare)
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Accumulation of DNA methylation alterations in paediatric glioma stem cells following fractionated dose irradiation
- 2020
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Ingår i: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7075 .- 1868-7083. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Radiation is an important therapeutic tool. However, radiotherapy has the potential to promote co-evolution of genetic and epigenetic changes that can drive tumour heterogeneity, formation of radioresistant cells and tumour relapse. There is a clinical need for a better understanding of DNA methylation alterations that may follow radiotherapy to be able to prevent the development of radiation-resistant cells. Methods We examined radiation-induced changes in DNA methylation profiles of paediatric glioma stem cells (GSCs) in vitro. Five GSC cultures were irradiated in vitro with repeated doses of 2 or 4 Gy. Radiation was given in 3 or 15 fractions. DNA methylation profiling using Illumina DNA methylation arrays was performed at 14 days post-radiation. The cellular characteristics were studied in parallel. Results Few fractions of radiation did not result in significant accumulation of DNA methylation alterations. However, extended dose fractionations changed DNA methylation profiles and induced thousands of differentially methylated positions, specifically in enhancer regions, sites involved in alternative splicing and in repetitive regions. Radiation induced dose-dependent morphological and proliferative alterations of the cells as a consequence of the radiation exposure. Conclusions DNA methylation alterations of sites with regulatory functions in proliferation and differentiation were identified, which may reflect cellular response to radiation stress through epigenetic reprogramming and differentiation cues.
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| 20. |
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| 21. |
- Edsbagge, Mikael, et al.
(författare)
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Spinal CSF absorption in healthy individuals.
- 2004
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Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 287:6
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Tidskriftsartikel (refereegranskat)abstract
- The present study examines the extent of spinal cerebrospinal fluid (CSF) absorption in healthy individuals in relation to physical activity, CSF production, intracranial pressure (ICP), and spinal CSF movement. Thirty-four healthy individuals aged 21-35 yr were examined by lumbar puncture and radionuclide cisternography with repeated imaging. ICP was registered before and after CSF drainage, and CSF production was calculated. Spinal CSF absorption was calculated as reduction in spinal radionuclide activity. The radionuclide activity in the spinal subarachnoidal space was gradually decreased by 20 +/- 13% (mean +/- SD) during 1 h. The reduction was higher in active than in resting individuals (27 +/- 12% vs. 13 +/- 9%). The mean ICP in 19 of the individuals was 13.6 +/- 3.1 cm H(2)O. B-waves were found in 79% of the individuals, with a mean frequency of 0.6 +/- 0.3 min(-1). The mean CSF production rate was 0.34 +/- 0.13 ml/min. There were no correlations between radionuclide reduction, spinal movement of the radionuclide, and CSF production rate. The spinal radionuclide reduction found in this study indicates a spinal CSF absorption of 0.11-0.23 ml/min, more pronounced in active than in resting individuals.
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| 22. |
- Farahmand, Dan, et al.
(författare)
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A double-blind randomized trial on the clinical effect of different shunt valve settings in idiopathic normal pressure hydrocephalus
- 2016
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Ingår i: Journal of Neurosurgery. - : Journal of Neurosurgery Publishing Group (JNSPG). - 0022-3085 .- 1933-0693. ; 124:2, s. 359-367
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE The study aim was to examine the effect of gradually reducing the opening pressure on symptoms and signs in the shunt treatment of idiopathic normal pressure hydrocephalus (iNPH). METHODS In this prospective double-blinded, randomized, controlled, double -center study on patients with iNPH, a ventriculoperitoneal shunt with an adjustable Codman Medos Valve was implanted in 68 patients randomized into 2 groups. In 1 group (the 20-4 group) the valve setting was initially set to 20 cm H2O and gradually reduced to 4 cm H2O over the course of the 6 -month study period. In the other group (the 12 group), the valve was kept at a medium level of 12 cm H2O during the whole study period. All patients were clinically evaluated using 4 tests preoperatively as well as postoperatively at 1, 2, 3, 4, and 6 months. The test scores between the 2 groups (20-4 and 12) were compared for each clinical evaluation. RESULTS Fifty-five patients (81%) were able to complete the study. There were no significant differences between the 2 groups (20-4 and 12) preoperatively or at any time postoperatively. Both groups exhibited significant clinical improvement after shunt insertion at all valve settings compared with the preoperative score, with the greatest improvement observed at the first postoperative evaluation. The clinical improvement was-significant within the first 3 months, and thereafter no significant improvement was seen in either group. CONCLUSIONS Gradual reduction of the valve setting from 20 to 4 cm H2O did not improve outcome compared with a fixed valve setting of 12 cm H2O. Improvement after shunt surgery in iNPH patients was evident within 3 months, irrespective of valve setting.
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| 23. |
- Farahmand, Dan, et al.
(författare)
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Endoscopic versus open microsurgery for colloid cysts of the third ventricle
- 2023
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Ingår i: British Journal of Neurosurgery. - : Informa UK Limited. - 0268-8697 .- 1360-046X. ; 37:1, s. 59-62
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The surgical approach for colloid cysts of the third ventricle mainly consists of endoscopic or microscopic approach but few studies compare the neurologic outcomes and complications related to the different approaches. We retrospectively reviewed our results after resection of colloid cysts of the third ventricle using endoscopic surgery (ES) compared to open microsurgery (OS). Methods Fifty-one patients were included in the study of which 17 patients underwent ES. Colloid cyst size and Evans' index were evaluated on CT or MRI scans. Presenting symptoms, neurologic outcomes and complications were compared between the two groups and analysed using Fisher's exact test. Operative time and days of hospital stay were compared between the two groups, using independent sample t-test. The median follow-up time was 96 days and did not differ significantly between the groups. Results Shorter mean operative time (p = 0.04) and fewer days of hospital stay (p < 0.01) were found in the endoscopic group compared to the open microsurgical group. Presenting symptoms, neurological outcomes and postoperative complications were similar in the two groups. Conclusions ES showed similar neurologic outcomes and complications compared to OS for colloid cysts of the third ventricle. ES showed significantly shorter operative times and hospital stays compared to OS.
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| 24. |
- Farahmand, Dan, et al.
(författare)
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Intracranial pressure in hydrocephalus: impact of shunt adjustments and body positions
- 2015
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Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 86:2, s. 222-228
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Tidskriftsartikel (refereegranskat)abstract
- Background The association between intracranial pressure (ICP) and different shunt valve opening pressures in relation to body positions is fundamental for understanding the physiological function of the shunt. Objective To analyse the ICP and ICP wave amplitude (AMP) at different shunt settings and body positions in patients with hydrocephalus. Methods In this prospective study 15 patients with communicating hydrocephalus were implanted with a ligated adjustable ventriculoperitoneal shunt. They also received a portable intraparenchymatous ICP-monitoring device. Postoperative ICP and AMP were recorded with the patients in three different body positions (supine, sitting and walking) and with the shunt ligated and open at high, medium and low valve settings. In each patient 12 10 min segments were coded, blinded and analysed for mean ICP and mean AMP using an automated computer algorithm. Results Mean ICP and mean AMP were lower at all three valve settings compared with the ligated shunt state (p<0.001). Overall, when compared with the supine position, mean ICP was 11.5 +/- 1.1 (mean +/- SD) mm Hg lower when sitting and 10.5 +/- 1.1 mm Hg lower when walking (p<0.001). Mean ICP was overall 1.1 mm Hg higher (p=0.042) when walking compared with sitting. The maximal adjustability difference (highest vs lowest valve setting) was 4.4 mm Hg. Conclusions Changing from a supine to an upright position reduced ICP while AMP only increased at trend level. Lowering of the shunt valve opening pressure decreased ICP and AMP but the difference in mean ICP in vivo between the highest and lowest opening pressures was less than half that previously observed in vitro.
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| 25. |
- Farahmand, Dan, et al.
(författare)
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Perioperative risk factors for short term shunt revisions in adult hydrocephalus patients.
- 2009
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 80:11, s. 1248-53
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to prospectively study perioperative variables associated with revision after shunt surgery for adult hydrocephalus. METHODS: Two protocols were designed to prospectively study perioperative risk factors during shunt insertion. Over 10 years (1995-2004), 450 adult (age >16 years) patients with first time shunt implantations were studied. Patients who had been treated with endoscopic third ventriculostomy were excluded from the study. All shunts were designated as meeting one of two end points: (1) shunt failure requiring revision within 6 months or (2) no shunt failure within 6 months. Shunt revision within 6 months postoperatively was considered to be related to the shunting procedure. RESULTS: 85 shunt revisions were performed within 6 months after insertion. During the study period the revision rate declined from 21.1% to 9.1%. Revision rates were the same for ventriculoperitoneal (n = 411) and ventriculoatrial (n = 39) shunts. The predictive values of variables related to the patient, operating room, surgical technique and shunt system were analysed to determine shunt outcome. CONCLUSIONS: Right frontal placement of the ventricular catheter was associated with the lowest rate of revisions. Adjustable valves were associated with a lower risk for shunt revision. Shunt revision rates did not differ between ventriculoperitoneal and ventriculoatrial shunts.
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| 26. |
- Fekete, Boglarka, et al.
(författare)
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The Gothenburg population-based glioblastoma research database: Methodological aspects and potential impact
- 2019
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Ingår i: Neurology and Neurosurgery. - 2631-4339. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Glioblastoma Multiforme (GBM) is the most frequently encountered malignant primary brain tumour. Population-based studies of GBM are still scarce. The current paper describes the design of a prospective population-based multidisciplinary research effort on GBM. Objective: To address the impact of a wide range of clinical parameters in relation to clinical outcome and survival in a population-based cohort of patients with GBM. Further, we aim to examine the role of established and novel biomarkers in tumour tissue and blood in relation to response to treatment and clinical outcome. Methods: This is a single institution, population-based study with consecutive inclusion of patients based on a presumed diagnosis of GBM following radiological diagnostic work-up and discussion at a multidisciplinary tumour conference. Clinical parameters and treatment-related parameters at disease onset and during follow-up, and survival will be recorded. Health-related quality of life and emotional wellbeing for patients and their relatives will be assessed. Fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tumour tissue is stored in an associated tissue biobank. Tissue micro-arrays are generated from representative areas of FFPE. Blood samples at admission for surgery and during follow-up are taken and stored frozen. Expected outcome: The study offers a multidisciplinary and translational approach to GBM research by linking a wide range of clinical parameters to biological parameters with high external validity. Thus, we expect to describe patterns of care and clinical course in a well-defined population-based cohort. Through a biomarker approach, we expect to 1) identify new biological subgroups of GBM, 2) explore and validate established and novel biomarkers for response to therapy, 3) estimate the proportion of patients suitable for targeted (“druggable”) therapy, and 4) explore and validate established and novel biomarkers for survival.
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| 27. |
- Fekete, Boglarka, et al.
(författare)
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What predicts survival in glioblastoma? A population-based study of changes in clinical management and outcome.
- 2023
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Ingår i: Frontiers in surgery. - 2296-875X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma is the most common and most aggressive primary brain tumor in adults. Despite multimodal treatment, the median survival time is 15-16 months and 5-year survival rate 5%-10%. The primary goal of this study was to identify prognostic factors for survival in an unselected population of patients operated for glioblastoma. The secondary goal was to explore changes in outcome and the clinical management of this patient group over time.We identified 222 consecutive adults operated for glioblastoma between November 2012 and June 2016 at the Department of Neurosurgery, Sahlgrenska University Hospital in Gothenburg, serving a health care region in the western part of Sweden with 1.900.000 inhabitants. Clinical variables were identified and tested as predictors for prognosis in extended Poisson regression models. The results were compared with a previously published cohort from 2004 to 2008, before current standard of care based on molecular tumor diagnosis was fully implemented.Median overall survival was 1.07 years, which was significantly longer than in the 2004-2008 cohort (1.07 vs. 0.73 y, age- and sex adjusted HR=1.89, p<0.0001). Variables associated with longer survival in the multivariable model were MGMT promoter hypermethylation, non-central tumor location, complete resection of enhancing tumor, WHO performance status 0-1, unilateral tumor location, fewer lobes involved, younger age and no comorbidities.The median survival for patients with glioblastoma treated according to current standard treatment has moderately but significantly increased, with MGMT promoter hypermethylation as the strongest predictor for survival.
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| 28. |
- Hellström, Per, et al.
(författare)
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Neuropsychological effects of shunt treatment in idiopathic normal pressure hydrocephalus.
- 2008
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Ingår i: Neurosurgery. - 1524-4040. ; 63:3
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To prospectively evaluate the effects of shunting on the neuropsychological performance of patients with idiopathic normal pressure hydrocephalus (INPH), to compare their performance with that of healthy individuals, and to estimate the predictive utility of putatively important factors. METHODS: A consecutive series of 47 patients with INPH underwent neurological, radiological, and neuropsychological examinations before and 3 months after shunt surgery. The same neuropsychological tests, measuring simple and target reaction times, dexterity, memory and learning, working memory, and aspects of executive functioning, were also administered to 159 healthy individuals. RESULTS: Performance on all neuropsychological tests, except Simple Reaction Time and Digit Span, significantly improved after surgery, with more severe functional deficits showing greatest improvement. Age, education, duration, vascular comorbidity, sex, and onset symptom all failed to predict the neuropsychological effects of treatment. Despite improvement 3 months after shunt surgery, INPH patients were still outperformed by healthy individuals. CONCLUSION: Most of the wide range of neuropsychological functions that are affected by INPH are markedly improved by shunt treatment, but not completely restored.
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| 29. |
- Hellström, Per, et al.
(författare)
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The neuropsychology of patients with clinically diagnosed idiopathic normal pressure hydrocephalus.
- 2007
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Ingår i: Neurosurgery. - : Ovid Technologies (Wolters Kluwer Health). - 1524-4040 .- 0148-396X. ; 61:6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare the neuropsychological performance of patients with idiopathic normal pressure hydrocephalus (INPH) with that of healthy individuals and to examine its relation to neurological signs, vascular comorbidity, and background factors. METHODS: A consecutive series of 58 patients with INPH underwent neurological, neuroradiological, and neuropsychological examinations. The neuropsychological tests, measuring vigilance, fine movements of the hands, learning, working memory, and aspects of executive functioning, were also administered to 108 healthy individuals. RESULTS: Patients performed worse than healthy individuals on all included tests. Significant correlations between test results were more frequent and stronger among patients and the degree of neuropsychological impairment was related to the severity of other signs of INPH. Patients with vascular risk factors performed worse than those without. CONCLUSION: The neuropsychological deficits in INPH are widely distributed, interrelated, associated with neurological signs, and aggravated by vascular comorbidity.
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| 30. |
- Herdell, V., et al.
(författare)
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Surgical outcomes of pediatric brain tumors in Sub-Saharan Africa: A systematic review
- 2022
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Ingår i: Brain and Spine. - : Elsevier BV. - 2772-5294. ; 2
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Pediatric Brain Tumors (PBT) are a common cause of cancer-related mortality globally. Contrary to high-income countries (HIC), survival rates in low-and-middle income countries (LMIC) remains low despite advances in neurosurgical care and diagnostics over the past decades. The aim of this systematic review was to investigate the surgical outcomes for PBT in Sub-Saharan Africa, and the distribution of PBT types.Methods: A systematic review was conducted on PubMed, for all available literature on the surgical outcomes of PBT in Sub-Saharan Africa, published before May 3, 2022. Two reviewers performed abstract, full text screening and data collection independently, resolving any conflicts by consensus.Results: The search yielded 256 studies, of which 22 met the inclusion criteria, amounting to a total of 243 pa-tients. Nigeria was the country with most data. Only subgroups of patients could be extracted from 12 studies, and variables of interest in 6 studies had inconsistent sample sizes. The age centered around 9 years, and there were approximately equal number of girls and boys. The most common tumor was medulloblastoma, followed by craniopharyngioma and astrocytoma. There was large heterogeneity in the reporting of outcomes, and a trend was difficult to discern, considering the large number of different tumor types and different extents of resection.Discussion and conclusion: Data is insufficient and inconsistent, precluding statistical conclusions. There is a need for more studies in the field.
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| 31. |
- Håkansson, Irene, et al.
(författare)
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Neurofilament levels, disease activity and brain volume during follow-up in multiple sclerosis
- 2018
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Ingår i: Journal of Neuroinflammation. - : BMC. - 1742-2094. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is a need for clinically useful biomarkers of disease activity in clinically isolated syndrome (CIS) and relapsing remitting MS (RRMS). The aim of this study was to assess the correlation between neurofilament light chain (NFL) in cerebrospinal fluid (CSF) and serum and the relationship between NFL and other biomarkers, subsequent disease activity, and brain volume loss in CIS and RRMS. Methods: A panel of neurodegenerative and neuroinflammatory markers were analyzed in repeated CSF samples from 41 patients with CIS or RRMS in a prospective longitudinal cohort study and from 22 healthy controls. NFL in serum was analyzed using a single-molecule array (Simoa) method. "No evidence of disease activity-3" (NEDA-3) status and brain volume (brain parenchymal fraction calculated using SyMRI (R)) were recorded during 4 years of follow-up. Results: NFL levels in CSF and serum correlated significantly (all samples, n = 63, r 0.74, p amp;lt; 0.001), but CSF-NFL showed an overall stronger association profile with NEDA-3 status, new T2 lesions, and brain volume loss. CSF-NFL was associated with both new T2 lesions and brain volume loss during follow-up, whereas CSF-CHI3L1 was associated mainly with brain volume loss and CXCL1, CXCL10, CXCL13, CCL22, and MMP-9 were associated mainly with new T2 lesions. Conclusions: Serum and CSF levels of NFL correlate, but CSF-NFL predicts and reflects disease activity better than S-NFL. CSF-NFL levels are associated with both new T2 lesions and brain volume loss. Our findings further add to the accumulating evidence that CSF-NFL is a clinically useful biomarker in CIS and RRMS and should be considered in the expanding NEDA concept. CSF-CXCL10 and CSF-CSF-CHI3L1 are potential markers of disease activity and brain volume loss, respectively.
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| 32. |
- Håkansson, Irene, et al.
(författare)
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Neurofilament light chain in cerebrospinal fluid and prediction of disease activity in clinically isolated syndrome and relapsing-remitting multiple sclerosis
- 2017
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 24:5, s. 703-712
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Improved biomarkers are needed to facilitate clinical decision-making and as surrogate endpoints in clinical trials in multiple sclerosis (MS). We assessed whether neurodegenerative and neuroinflammatory markers in cerebrospinal fluid (CSF) at initial sampling could predict disease activity during 2 years of follow-up in patients with clinically isolated syndrome (CIS) and relapsing-remitting MS. Methods: Using multiplex bead array and enzyme-linked immunosorbent assay, CXCL1, CXCL8, CXCL10, CXCL13, CCL20, CCL22, neurofilament light chain (NFL), neurofilament heavy chain, glial fibrillary acidic protein, chitinase-3-like-1, matrix metalloproteinase-9 and osteopontin were analysed in CSF from 41 patients with CIS or relapsing-remitting MS and 22 healthy controls. Disease activity (relapses, magnetic resonance imaging activity or disability worsening) in patients was recorded during 2 years of follow-up in this prospective longitudinal cohort study. Results: In a logistic regression analysis model, NFL in CSF at baseline emerged as the best predictive marker, correctly classifying 93% of patients who showed evidence of disease activity during 2 years of follow-up and 67% of patients who did not, with an overall proportion of 85% (33 of 39 patients) correctly classified. Combining NFL with either neurofilament heavy chain or osteopontin resulted in 87% overall correctly classified patients, whereas combining NFL with a chemokine did not improve results. Conclusions: This study demonstrates the potential prognostic value of NFL in baseline CSF in CIS and relapsing-remitting MS and supports its use as a predictive biomarker of disease activity.
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| 33. |
- Kamtchum-Tatuene, J., et al.
(författare)
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A 42-year-old woman with subacute reversible dementia: A cautionary tale
- 2017
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Ingår i: Malawi Medical Journal. - : African Journals Online (AJOL). - 1995-7262. ; 29:3, s. 265-267
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Tidskriftsartikel (refereegranskat)abstract
- A 42-year-old woman presented with a 6-month history of diffuse headache of moderate intensity and gradual onset of generalized weakness, imbalance, apathy, memory decline, hypophonia, dysphagia, constipation and urinary incontinence. Clinical examination revealed several elements of a frontal lobe dysfunction including apathy with motor impersistence, presence of primitive reflexes, generalized hyperreflexia with bilateral Hoffman sign and ankle clonus. The biological workup was unremarkable and a brain computed tomography scan identified a giant olfactory groove meningioma. A prompt neurosurgical intervention helped to reverse the symptoms. This case illustrates the benefits of actively looking for treatable conditions in young patients presenting with acute or subacute dementia and emphasizes the pivotal role of early brain imaging.
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| 34. |
- Lilja-Lund, Otto, 1981-
(författare)
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A population-based study on neuropsychological and morphological signs of idiopathic normal pressure hydrocephalus
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is typically manifested in people over 65 years. The condition of gait disturbances, incontinence, and cognitive dysfunction can be reversed in up to 80% of the cases by ventricular shunting. Neuropsychological testing and standardized brain imaging of signs of iNPH are essential to detect and define the progression. The aims of this thesis were to develop a radiological iNPH scale, examine how morphological features relate to symptoms of iNPH, investigate if dual-task testing (e.g., walking and talking) is helpful in detecting iNPH, and monitor developing symptoms over two years.METHOD: The studies include 168 participants (median [range] age 73 [66–92]) at baseline (2014/2015) and 104 participants (age 75 [68–91]) at follow-up (2016/2017) from the general population. Neuropsychological tests of executive functions, memory, and motor performance, and computed tomography (CT) for brain imaging were used.RESULTS: Seven morphological features were combined into a scoring scale for iNPH. The total score correlated with clinical symptoms (r = -0.40, p <.001). All core symptoms were associated to wider temporal horns (TH) (p <.01). Participants with iNPH stopped walking to talk more frequently (p = .044). Participants who developed iNPH during the study worsened more on declarative memory (ES -0.37).DISCUSSION: The Radscale was related to symptoms of iNPH and the TH to all main clinical features. Difficulties walking while recalling a previous event, worsened declarative memory, and expanding ventricular space surrounding the hippocampus were noticeable signs of iNPH. Memory functions are important to recognize in iNPH.
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| 35. |
- Mellergård, Johan, et al.
(författare)
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Association between Change in Normal Appearing White Matter Metabolites and Intrathecal Inflammation in Natalizumab-Treated Multiple Sclerosis
- 2012
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple sclerosis (MS) is associated not only with focal inflammatory lesions but also diffuse pathology in the central nervous system (CNS). Since there is no firm association between the amount of focal inflammatory lesions and disease severity, diffuse pathology in normal appearing white matter (NAWM) may be crucial for disease progression. Immunomodulating treatments for MS reduce the number of focal lesions, but possible effects on diffuse white matter pathology are less studied. Furthermore, it is not known whether intrathecal levels of inflammatory or neurodegenerative markers are associated with development of pathology in NAWM. Methods: Quantitative proton magnetic resonance spectroscopy (H-1-MRS) was used to investigate NAWM in 27 patients with relapsing MS before and after one year of treatment with natalizumab as well as NAWM in 20 healthy controls at baseline. Changes in H-1-MRS metabolite concentrations during treatment were also correlated with a panel of intrathecal markers of inflammation and neurodegeneration in 24 of these 27 patients. Results: The group levels of H-1-MRS metabolite concentrations were unchanged pre-to posttreatment, but a pattern of high magnitude correlation coefficients (r = 0.43-0.67, p<0.0005-0.03) were found between changes in individual metabolite concentrations (total creatine and total choline) and levels of pro-inflammatory markers (IL-1 beta and CXCL8). Conclusions: Despite a clinical improvement and a global decrease in levels of inflammatory markers in cerebrospinal fluid during treatment, high levels of pro-inflammatory CXCL8 and IL-1 beta were associated with an increase in H-1-MRS metabolites indicative of continued gliosis development and membrane turnover in NAWM.
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| 36. |
- Mellergård, Johan, et al.
(författare)
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Cerebrospinal fluid levels of neurofilament and tau correlate with brain atrophy in natalizumab-treated multiple sclerosis
- 2017
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 24:1, s. 112-121
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Brain atrophy is related to clinical deterioration in multiple sclerosis (MS) but its association with intrathecal markers of inflammation or neurodegeneration is unclear. Our aim was to investigate whether cerebrospinal fluid (CSF) markers of inflammation or neurodegeneration are associated with brain volume change in natalizumab-treated MS and whether this change is reflected in non-lesional white matter metabolites. Methods: About 25 patients with natalizumab-treated MS were followed for 3 years with assessment of percentage brain volume change (PBVC) and absolute quantification of metabolites with proton magnetic resonance spectroscopy (1 H MRS). Analyses of inflammatory [interleukin 1 beta (IL-1 beta), IL-6, C-X-C motif chemokine 8 (CXCL8), CXCL10, CXCL11, C-C motif chemokine 22] and neurodegenerative [neurofilament light protein (NFL), glial fibrillary acidic protein, myelin basic protein, tau proteins] markers were done at baseline and 1-year follow-up. Results: The mean decline in PBVC was 3% at the 3-year follow-up, although mean H-1 MRS metabolite levels in non-lesional white matter were unchanged. CSF levels of NFL and tau at baseline correlated negatively with PBVC over 3 years (r = -0.564, P = 0.012, and r = -0.592, P = 0.010, respectively). Conclusions: A significant 3-year whole-brain atrophy was not reflected in mean metabolite change of non-lesional white matter. In addition, our results suggest that CSF levels of NFL and tau correlate with brain atrophy development and may be used for evaluating treatment response in inflammatory active MS.
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| 37. |
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| 38. |
- Nilsson, Daniel, 1973, et al.
(författare)
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Decreased head circumference in shunt-treated compared with healthy children
- 2013
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Ingår i: Journal of Neurosurgery-Pediatrics. - : Journal of Neurosurgery Publishing Group (JNSPG). - 1933-0707 .- 1933-0715. ; 12:5, s. 483-490
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Tidskriftsartikel (refereegranskat)abstract
- Object. In this study, the authors' goal was to compare head circumference in hydrocephalic children during the first 4 years of ventriculoperitoneal (VP) shunt treatment with data on healthy children and to investigate predictors of skull growth in children with a VP shunt. Methods. Children from western Sweden treated for hydrocephalus with an initial VP shunt insertion performed between 2001 and 2006 who were younger than 12 months of age at the time of surgery were included. Children with major brain malformations, craniofacial syndromes, large cysts, and tumors were excluded. Head circumference, weight, and height at 9 defined ages up to 4 years were obtained and compared with data from a reference population of 3650 healthy children using the standard deviation score (SDS). Predictors (length, weight, etiology of hydrocephalus, valve type, number of revisions, valve setting, number of adjustments, and time of first surgery) for head circumference SDS and changes in head circumference SDS from shunt insertion at 1 year to last measurement were analyzed using bivariate and multiple linear regression analysis. Results. Fifty children were included. The mean SDSs for head circumference in shunt-treated compared with healthy children were 1.95 +/- 2.50 at shunt insertion (p < 0.001, n = 44), 0.38 +/- 1.97 at 1 year (p = 0.27, n = 33), -0.96 +/- 2.05 at 2 years (p = 0.046, n = 21), -1.39 +/- 2.25 at 3 years (p = 0.026, n = 16), and 0.63 +/- 3.34 at 4 years (p = 0.73, n = 4). Significant predictors for low head circumference SDS at 1 year of age were low weight (p = 0.002) and short height (p = 0.022) and at last measurement low weight (p < 0.0001), short height (p = 0.002), and 1-4 shunt revisions (p = 0.034). A significant predictor for change in head circumference SDS from shunt insertion to 1 year of age was the number of shunt valve revisions (p = 0.04) and at last measurement an etiology of intraventricular hemorrhage (p = 0.0058). Conclusions. Shunt-treated children have smaller head circumferences at 2 and 3 years of age than healthy children. Low weight, short height, etiology of intraventricular hemorrhage, and frequent shunt valve revisions are predictors for decreased head circumference. Prospective, randomized studies comparing skull growth using fixed and adjustable pressure-regulated shunt valves and flow-regulated valves are needed.
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| 39. |
- Rabiei, Katrin, 1979, et al.
(författare)
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Diverse arachnoid cyst morphology indicates different pathophysiological origins
- 2014
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Ingår i: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background There are few, limited, and to some extent contradictory, reports on the cellular and subcellular morphology of arachnoid cysts. In the literature cyst membranes are described as similar to, or as vastly different from, normal arachnoid membranes. Methods This paper reports electron microscopic analyses of symptomatic cysts from 24 patients (12 males and 12 females; age 10–79), that underwent fenestration surgery. Fourteen cysts were located in the middle cranial fossa (temporal), one in the interpeduncular cistern, five in the posterior fossa, and four were overlying the frontal cortex. Results Microscopic findings confirmed the diverse nature of this clinical condition. Twelve cyst walls resembled normal arachnoid, four had a conspicuous core of dense fibrous tissue with a simple epithelial lining, and the remaining aberrant cysts exhibited non-arachnoid luminal epithelia with plentiful microvilli and/or cilia, and also nervous tissue components in the wall. The possible identity and origin of various cyst types are discussed. We hypothesize that cysts are formed mostly at an early stage of embryonic development, as a teratological event. Conclusions Cysts with various epithelial linings and extracellular components most likely have different barrier properties and fluid turnover characteristics. Further studies are needed to elucidate relations between cyst morphology, fluid composition, pathogenesis, and clinical behaviour including growth rate and relapse tendency.
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| 40. |
- Rabiei, Katrin, 1979, et al.
(författare)
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Does subjective improvement in adults with intracranial arachnoid cysts justify surgical treatment?
- 2018
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Ingår i: Journal of Neurosurgery. - 0022-3085. ; 128:1, s. 250-257
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Subjective improvement of patients who have undergone surgery for intracranial arachnoid cysts has justifed surgical treatment. The current study aimed to evaluate the outcome of surgical treatment for arachnoid cysts using standardized interviews and assessments of neuropsychological function and balance. The relationship between arachnoid cyst location, postoperative improvement, and arachnoid cyst volume was also examined. METHODS The authors performed a prospective, population-based study. One hundred nine patients underwent neurological, neuropsychological, and physiotherapeutic examinations. The arachnoid cysts were considered symptomatic in 75 patients, 53 of whom agreed to undergo surgery. In 32 patients, results of the differential diagnosis revealed that the symptoms were due to a different underlying condition and were unrelated to an arachnoid cyst. Neuropsychological testing included target reaction time, Grooved Pegboard, Rey Auditory Verbal Learning, Rey Osterrieth complex fgure, and Stroop tests. Balance tests included the extended Falls Effcacy Scale, Romberg, and sharpened Romberg with open and closed eyes. The tests were repeated 5 months postoperatively. Cyst volume was pre-and postoperatively measured using OsiriX software. RESULTS Patients who underwent surgery did not have results on balance and neuropsychological tests that were different from patients who declined or had symptoms unrelated to the arachnoid cyst. Patients with a temporal arachnoid cyst performed within the normal range on the neuropsychological tests. Seventy-seven percent of the patients who underwent surgery reported improvement, yet there were no differences in test results before and after surgery. Arachnoid cysts in the temporal region and posterior fossa did not influence the preoperative results of neuropsychological and motor tests. The arachnoid cyst volume decreased postoperatively (p <∗0.0001), but there was no relationship between volume reduction and clinical improvement. CONCLUSIONS The results of this study speak against objectively verifable improvement following surgical treatment in adults with intracranial arachnoid cysts. © AANS 2018.
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| 41. |
- Rabiei, Katrin, 1979, et al.
(författare)
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Surgery for intracranial arachnoid cysts in children—a prospective long-term study
- 2016
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Ingår i: Child's Nervous System. - : Springer Science and Business Media LLC. - 0256-7040 .- 1433-0350. ; 32, s. 1257-1263
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Tidskriftsartikel (refereegranskat)abstract
- © 2016, Springer-Verlag Berlin Heidelberg. Purpose: Intracranial arachnoid cysts are cystic malformations found in both adults and children. While many are asymptomatic, some cause symptoms and warrant surgical treatment. In this prospective population-based study, we aimed to study the short- and long-term outcome after surgical intervention in children with arachnoid cysts referred to our centre. Methods: Twenty-seven pediatric patients (13 f. 14 m, mean age 9.4years) with de novo cysts were consecutively included during a 5-year period. The presenting symptoms were headache (n=12), balance disturbance and dizziness (n=6), seizures (n=6), hydrocephalus (n=5), and macrocephaly (n=1). Twenty-two patients underwent surgical treatment with either microsurgical (n=17) or endoscopic fenestration (n=5) of the cyst wall. Cyst volume was measured with OsiriX® software pre- and postoperatively. Short-term and long-term follow-up of all patients was conducted 3months and 8.6years (7–10.5years) postoperatively. Results: Three months after surgery, 59% of the patients were improved regarding at least one major complaint, and average cyst volume was reduced to 33.3ml (0–145ml). At the long-term follow-up of 8.6years, 77% of the patients were improved regarding at least one symptom but subjective symptoms remained in 59%. There was no permanent postoperative morbidity. We found no association between radiological reduction of cyst volume and clinical improvement. Conclusion: Our findings support a restrictive attitude to surgery for intracranial arachnoid cysts, in the absence of objectively verified symptoms and signs or obstruction of CSF pathways.
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- Saehle, T., et al.
(författare)
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A randomized controlled dual-center trial on shunt complications in idiopathic normal-pressure hydrocephalus treated with gradually reduced or "fixed" pressure valve settings
- 2014
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Ingår i: Journal of Neurosurgery. - : Journal of Neurosurgery Publishing Group (JNSPG). - 0022-3085 .- 1933-0693. ; 121:5, s. 1257-1263
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Tidskriftsartikel (refereegranskat)abstract
- Object. This study was undertaken to investigate whether a gradual reduction of the valve setting (opening pressure) decreases the complication rate in patients with idiopathic normal-pressure hydrocephalus (iNPH) treated with a ventriculoperitoneal (VP) shunt. Methods. In this prospective double-blinded, randomized, controlled, dual-center study, a VP shunt with an adjustable valve was implanted in 68 patients with iNPH, randomized into two groups. In one group (the 20-4 group) the valve setting was initially set to 20 cm H2O and gradually reduced to 4 cm H2O over the course of the 6-month study period. In the other group (the 12 group), the valve was kept at a medium pressure setting of 12 cm H2O during the whole study period. The time to and type of complications (hematoma, infection, and mechanical problems) as well as overdrainage symptoms were recorded. Symptoms, signs, and outcome were assessed by means of the iNPH scale and the NPH grading scale. Results. Six patients in the 20-4 group (22%) and 7 patients in the 12 group (23%) experienced a shunt complication; 9 had subdural hematomas, 3 mechanical obstructions, and I infection (no significant difference between groups). The frequency of overdrainage symptoms was significantly higher for a valve setting <= 12 cm H2O compared with a setting > 12 cm H2O. The 20-4 group had a higher improvement rate (88%) than the 12 group (62%) (p = 0.032). There was no significant relationship between complications and body mass index, the use of an antisiphon device, or the use of anticoagulants. Conclusions. Gradual lowering of the valve setting to a mean of 7 cm H2O led to the same rate of shunt complications and overdrainage symptoms as a fixed valve setting at a mean of 13 cm H2O but was associated with a significantly better outcome.
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| 43. |
- Schepke, Elizabeth, et al.
(författare)
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Effects of the growth pattern of medulloblastoma on short-term neurological impairments after surgery: results from the prospective multicenter HIT-SIOP PNET 4 study
- 2020
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Ingår i: Journal of Neurosurgery-Pediatrics. - 1933-0707. ; 25:4, s. 425-433
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Extensive resection of a tumor in the posterior fossa in children is associated with the risk of neurological deficits. The objective of this study was to prospectively evaluate the short-term neurological morbidity in children after medulloblastoma surgery and relate this to the tumor's growth pattern and to the extent of resection. METHODS In 160 patients taking part in the HIT-STOP PNET 4 (Hyperfractionated Versus Conventionally Fractionated Radiotherapy in Standard Risk Medulloblastoma) trial, neurosurgeons prospectively responded to questions concerning the growth pattern of the tumor they had resected. The extent of resection (gross, near, or subtotal) was evaluated using MRI. The patients' neurological status before resection and around 30 days after resection was recorded. RESULTS Invasive tumor growth, defined as local invasion in the brain or meninges, cranial nerve, or major vessel, was reported in 58% of the patients. After surgery almost 70% of all patients were affected by one or several neurological impairments (e.g., impaired vision, impaired extraocular movements, and ataxia). However, this figure was very similar to the preoperative findings. Invasive tumor growth implied a significantly higher number of impairments after surgery (p = 0.03) and greater deterioration regarding extraocular movements (p = 0.012), facial weakness (p = 0.048), and ataxia in the arms (p = 0.014) and trunk (p = 0.025) compared with noninvasive tumor growth. This deterioration was not dependent on the extent of resection performed. Progression-free survival (PFS) at 5 years was 80% +/- 4% and 76% +/- 5% for patients with invasive and noninvasive tumor growth, respectively, with no difference in the 5-year PFS for extent of resection. CONCLUSIONS Preoperative neurological impairments and invasive tumor growth were strong predictors of deterioration in short-term neurological outcome after medulloblastoma neurosurgery, whereas the extent of resection was not . Neither tumor invasiveness nor extent of resection influenced PFS. These findings support the continuation of maximal safe resection in medulloblastoma surgery where functional risks are not taken in areas with tumor invasion.
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