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  • 1.
    Axelson, Hans
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Neurophysiology.
    Latini, Francesco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Jemstedt, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Continuous subcortical language mapping in awake glioma surgery2022In: Frontiers in Oncology, E-ISSN 2234-943X, Vol. 12, article id 947119Article in journal (Refereed)
    Abstract [en]

    Repetitive monopolar short-train stimulation (STS) delivered from a suction probe enables continuous mapping and distance assessment of corticospinal tracts during asleep glioma resection. In this study, we explored this stimulation technique in awake glioma surgery. Fourteen patients with glioma involving language-related tracts were prospectively included. Continuous (3-Hz) cathodal monopolar STS (five pulses, 250 Hz) was delivered via the tip of a suction probe throughout tumor resection while testing language performance. At 70 subcortical locations, surgery was paused to deliver STS in a steady suction probe position. Monopolar STS influence on language performance at different subcortical locations was separated into three groups. Group 1 represented locations where STS did not produce language disturbance. Groups 2 and 3 represented subcortical locations where STS produced language interference at different threshold intensities (>= 7.5 and <= 5 mA, respectively). For validation, bipolar Penfield stimulation (PS; 60 Hz for 3 s) was used as a "gold standard" comparison method to detect close proximity to language-related tracts and classified as positive or negative regarding language interference. There was no language interference from STS in 28 locations (Group 1), and PS was negative for all sites. In Group 2 (STS threshold >= 7.5 mA; median, 10 mA), there was language interference at 18 locations, and PS (median, 4 mA) was positive in only one location. In Group 3 (STS threshold <= 5 mA; median, 5 mA), there was language interference at 24 locations, and positive PS (median 4 mA) was significantly (p < 0.01) more common (15 out of 24 locations) compared with Groups 1 and 2. Despite the continuous stimulation throughout tumor resection, there were no seizures in any of the patients. In five patients, temporary current spread to the facial nerve was observed. We conclude that continuous subcortical STS is feasibly also in awake glioma surgery and that no language interference from STS or interference at >= 7.5 mA seems to indicate safe distance to language tracts as judged by PS comparisons. STS language interference at STS <= 5 mA was not consistently confirmed by PS, which needs to be addressed.

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    FULLTEXT01
  • 2.
    Basma, Jaafar
    et al.
    St Vincents Infirm Med Ctr, Arkansas Neurosci Inst, Little Rock, AR 72205 USA..
    Latini, Francesco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. St Vincents Infirm Med Ctr, Arkansas Neurosci Inst, Little Rock, AR 72205 USA.;S Anna Univ Hosp, Dept Neurosci & Rehabil, Div Neurosurg, Ferrara, Italy..
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. St Vincents Infirm Med Ctr, Arkansas Neurosci Inst, Little Rock, AR 72205 USA..
    Abuelem, Tarek
    St Vincents Infirm Med Ctr, Arkansas Neurosci Inst, Little Rock, AR 72205 USA..
    Krisht, Ali Fadl
    St Vincents Infirm Med Ctr, Arkansas Neurosci Inst, Little Rock, AR 72205 USA..
    Minimizing Collateral Brain Injury Using a Protective Layer of Fibrin Glue: Technical Note2015In: World Neurosurgery, ISSN 1878-8750, E-ISSN 1878-8769, Vol. 84, no 6, p. 2030-2036Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Neurosurgical procedures expose the brain surface to a constant risk of collateral injury. We describe a technique where the brain surface is covered with a protective layer of fibrin glue and discuss its advantages. METHODS: A thin layer of fibrin glue was applied on the brain surface after its exposure in 34 patients who underwent different craniotomies for tumoral and vascular lesions. Data of 35 more patients who underwent standard microsurgical technique were collected as a control group. Cortical and pial injuries were evaluated using an intra-operative visual scale. Eventual abnormal signals at the early postoperative T2-weighted fluid-attenuated inversion recovery (T2FLAIR) magnetic resonance imaging (MRI) sequences were evaluated in oncological patients. RESULTS: Total pial injury was noted in 63% of cases where fibrin glue was not used. In cases where fibrin glue was applied, a significantly lower percentage of 26% (P < 0.01) had pial injuries. Only 9% had injuries in areas covered with fibrin glue (P < 0.0001). Early postoperative T2FLAIR MRI confirmed the differences of altered signal around the surgical field in the two populations. CONCLUSION: We propose beside an appropriate and careful microsurgical technique the possible use of fibrin glue as alternative, safe, and helpful protection during complex microsurgical dissections. Its intrinsic features allow the neurosurgeon to minimize the cortical manipulation preventing minor collateral brain injury.

  • 3. Basma, Jaafar
    et al.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Latini, Francesco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Pravdenkova, Svetlana
    Krisht, Ali
    Mobilization of the Transcavernous Oculomotor Nerve During Basilar Aneurysm Surgery: Biomechanical Bases for Better Outcome2014In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 10, no 1, p. 106-114Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The transcavernous approach adds a significant exposure advantage in basilar aneurysm surgery. However, one of its frequently reported side effects is postoperative oculomotor nerve palsy. OBJECTIVE: To present the technique of mobilizing the oculomotor nerve throughout its intracranial course and to analyze its consequences on the nerve tension and clinical outcome. METHODS: The oculomotor nerve is mobilized from its mesencephalic origin to the superior orbital fissure. Its degree of mobility, related to the imposed pulling force, was measured in 11 cadaveric nerves. Tension was mathematically deduced and compared before and after mobilizing of the cavernous segment. One hundred four patients treated for basilar aneurysms with the orbitozygomatic pretemporal transcavernous approach were followed up for a 1-year period and evaluated for postoperative oculomotor nerve palsy. RESULTS: Releasing the transcavernous segment compared to cisternal mobilization alone resulted in a significant increase in freedom of mobility from 4 to 7.9 mm (P < .001) and in a significant decrease in tension from 0.8 to 0.5 N (P = .006). Ninety-nine percent of aneurysms treated with this technique were amenable to neck clipping, and a total of 84% of patients had a good postoperative outcome (modified Rankin Scale score, 0-2). All patients showed direct postoperative palsy; however, 97% had a complete recovery by 9 months. Only 3 patients had a persistent diplopia on medial gaze, which was corrected with prism glasses. CONCLUSION: Mobilization of the transcavernous oculomotor nerve results in better maneuverability and less tension on the nerve, which lead to successful surgical treatment and favorable oculomotor outcome.

  • 4.
    Johansson, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Cesarini, Kristina G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Contant, C F
    Persson, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Changes in intervention and outcome in elderly patients with subarachnoid hemorrhage.2001In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 32, no 12Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: The elderly constitute a significant and increasing proportion of the population. The aim of this investigation was to study time trends in clinical management and outcome in elderly patients with subarachnoid hemorrhage.

    METHODS: Two hundred eighty-one patients >/=65 years of age with aneurysmal subarachnoid hemorrhage who were accepted for treatment at the Uppsala University Hospital neurosurgery clinic during 1981 to 1998 were included. Hunt and Hess grades on admission, specific management components, and clinical outcomes were recorded. Three periods were compared: A, 1981 to 1986 (before neurointensive care); B, 1987 to 1992; and C, 1993 to 1998.

    RESULTS: The volume of elderly patients (>/=65 years of age) increased with time, especially patients >/=70 years of age. Furthermore the proportion of patients with more severe clinical conditions increased. A greater proportion of patients had a favorable outcome (A, 45%; B, 61%; C, 58%) despite older ages and more severe neurological and clinical conditions. In period C, Hunt and Hess I to II patients had a favorable outcome in 85% of cases compared with 64% in period A. This was achieved without any increase in the number of severely disabled patients.

    CONCLUSIONS: Elderly patients with subarachnoid hemorrhage can be treated successfully, and results are still improving. The introduction of neurointensive care may have contributed to the improved outcome without increasing the proportion of severely disabled patients. A defeatist attitude toward elderly patients with this otherwise devastating disease is not justified.

  • 5.
    Johansson, Mats
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Neurokirurgi.
    Norbäck, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Neurokirurgi.
    Gal, G
    Department of Oncology, Radiology and Clinical Immunology. Neuroröntgen.
    Cesarini, Kristina G.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Neurokirurgi.
    Tovi, Metin
    Department of Oncology, Radiology and Clinical Immunology.
    Solander, Sten
    Department of Oncology, Radiology and Clinical Immunology.
    Contant, Charlie
    Neurokirurgi.
    Ronne-Engström, Elisabeth
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Neurokirurgi.
    Enblad, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Neurokirurgi.
    Clinical outcome after endovascular coil embolization in elderly patients with subarachnoid hemorrhage2004In: Neuroradiology: Interventional Neuroradiology, Vol. 46, p. 385-391Article in journal (Refereed)
  • 6.
    Johansson, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Norbäck, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Gál, Gyula
    Cesarini, Kristina G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Tovi, Metin
    Solander, Sten
    Contant, C F
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Clinical outcome after endovascular coil embolization in elderly patients with subarachnoid hemorrhage.2004In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 46, no 5Article in journal (Refereed)
    Abstract [en]

    Subarachnoid hemorrhage (SAH) is not an unusual disease in an elderly population. The clinical outcome has improved over time. It has been suggested that elderly SAH patients would benefit from endovascular aneurysm treatment. The aim of this study was to evaluate technical results and clinical outcome in a series of elderly SAH-patients treated with endovascular coil embolization. Sixty-two patients (> or = 65 years) presenting with aneurysmal SAH underwent early endovascular coil embolization at Uppsala University Hospital between September 1996 and December 2000. In all 62 cases included in the study, endovascular coil embolization was considered the first line of treatment. Admission variables, specific information on technical success, degree of occlusion and procedural complications, and outcome figures were recorded. Clinical grade on admission was Hunt and Hess (H&H) I-II in 39%, H&H III in 27% and H&H IV-V in 34% of the patients. The proportion of posterior circulation aneurysms was 24%. Coil embolization was successfully completed in 94%. The degree of occlusion of the treated aneurysm was complete occlusion in 56%, neck remnant in 21%, residual filling in 11%, other remnant in 5% and not treated in 6%. The rate of procedural complications was 11%. Outcome after 6 months was favorable in 41%, severe disability in 36% and poor in 22%. Favorable outcome was achieved in 57% of the H&H I-II patients, 47% of the H&H III patients and 17% of the H&H IV-V patients. Endovascular aneurysm treatment can be performed in elderly patients with SAH with a high level of technical success, acceptable aneurysm occlusion results, an acceptable rate of procedural complications and fair outcome results.

  • 7.
    Latini, Francesco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Axelson, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Jemstedt, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Alberius Munkhammar, åsa
    Uppsala Univ Hosp, Rehabil & Pain Ctr, S-75185 Uppsala, Sweden..
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Role of Preoperative Assessment in Predicting Tumor-Induced Plasticity in Patients with Diffuse Gliomas2021In: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 10, no 5, article id 1108Article in journal (Refereed)
    Abstract [en]

    When diffuse gliomas (DG) affect the brain's potential to reorganize functional networks, patients can exhibit seizures and/or language/cognitive impairment. The tumor-brain interaction and the individual connectomic organization cannot be predicted preoperatively. We aimed to, first, investigate the relationship between preoperative assessment and intraoperative findings of eloquent tumors in 36 DG operated with awake surgery. Second, we also studied possible mechanisms of tumor-induced brain reorganization in these patients. FLAIR-MRI sequences were used for tumor volume segmentation and the Brain-Grid system (BG) was used as an overlay for infiltration analysis. Neuropsychological (NPS) and/or language assessments were performed in all patients. The distance between eloquent spots and tumor margins was measured. All variables were used for correlation and logistic regression analyses. Eloquent tumors were detected in 75% of the patients with no single variable able to predict this finding. Impaired NPS functions correlated with invasive tumors, crucial location (A4C2S2/A3C2S2-voxels, left opercular-insular/sub-insular region) and higher risk of eloquent tumors. Epilepsy was correlated with larger tumor volumes and infiltrated A4C2S2/A3C2S2 voxels. Language impairment was correlated with infiltrated A3C2S2 voxel. Peritumoral cortical eloquent spots reflected an early compensative mechanism with age as possible influencing factor. Preoperative NPS impairment is linked with high risk of eloquent tumors. A systematic integration of extensive cognitive assessment and advanced neuroimaging can improve our comprehension of the connectomic brain organization at the individual scale and lead to a better oncological/functional balance.

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    FULLTEXT01
  • 8.
    Latini, Francesco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Basma, Jaafar
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Krisht, Ali Fadl
    Epidural skull base approach for dural arteriovenous fistulas (DAVF) of the anterior and middle cranial fossa2014In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 156, no 1, p. 93-95Article in journal (Refereed)
  • 9.
    Latini, Francesco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Beháňová, Andrea
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
    Sintorn, Ida-Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
    Hodik, Monika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Staxäng, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    The link between gliomas infiltration and white matter architecture investigated with electron microscopy and diffusion tensor imaging2021In: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 31, p. 102735-Article in journal (Refereed)
    Abstract [en]

    Diffuse low-grade gliomas display preferential locations in eloquent and secondary associative brain areas. The reason for this tendency is still unknown. We hypothesized that the intrinsic architecture and water diffusion properties of the white matter bundles in these regions may facilitate gliomas infiltration. Magnetic resonance imaging of one hundred and two low-grade gliomas patients were normalized to/and segmented in MNI space to create a probabilistic infiltration weighted gradient map. Diffusion tensor imaging (DTI)- based parameters were derived for five major white matter bundles, displaying high- and low grade of infiltration, (corpus callosum, cingulum, arcuate fasciculus, inferior fronto-occipital fasciculus and cortico-spinal tract), averaged over 20 healthy individuals acquired from the Human connectome project (HCP) database. Transmission electron microscopy (TEM) was used to analyze fiber density, diameter and g-ratio in 100 human white matter regions, sampled from cadaver specimens, reflecting areas with different gliomas infiltration frequency. Histological results and DTI-based parameters were compared in anatomical regions of high- and low grade of infiltration respectively. We detected differences in the infiltration frequency of five major white matter bundles. Regional differences within the same white matter bundles were detected by both TEM- and DTI analysis. Regions with high infiltration frequency (HIF) displayed a higher fiber density, smaller fiber diameter but higher myelin thickness and lower axial diffusivity compare compared with low infiltration frequency (LIF) regions. Our results  seem to indicate that the fiber diameter, myelin thickness and the  possible organization of the fibers are different in HIF compared to LIF regions and may be linked to the preferential location of diffuse low-grade gliomas.

  • 10.
    Latini, Francesco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Berntsson, Shala G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Institute of Neuroscience and Physiology, Department of Clinical Neuroscience, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    A novel radiological classification system for cerebral gliomas: The Brain-Grid2019In: PLOS ONE, E-ISSN 1932-6203, Vol. 14, no 1, article id e0211243Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Standard radiological/topographical classifications of gliomas often do not reflect the real extension of the tumor within the lobar-cortical anatomy. Furthermore, these systems do not provide information on the relationship between tumor growth and the subcortical white matter architecture. We propose the use of an anatomically standardized grid system (the Brain-Grid) to merge serial morphological magnetic resonance imaging (MRI) scans with a representative tractographic atlas. Two illustrative cases are presented to show the potential advantages of this classification system.

    METHODS: MRI scans of 39 patients (WHO grade II and III gliomas) were analyzed with a standardized grid created by intersecting longitudinal lines on the axial, sagittal, and coronal planes. The anatomical landmarks were chosen from an average brain, spatially normalized to the Montreal Neurological Institute (MNI) space and the Talairach space. Major white matter pathways were reconstructed with a deterministic tracking algorithm on a reference atlas and analyzed using the Brain-Grid system.

    RESULTS: In all, 48 brain grid voxels (areas defined by 3 coordinates, axial (A), coronal (C), sagittal (S) and numbers from 1 to 4) were delineated in each MRI sequence and on the tractographic atlas. The number of grid voxels infiltrated was consistent, also in the MNI space. The sub-cortical insula/basal ganglia (A3-C2-S2) and the fronto-insular region (A3-C2-S1) were most frequently involved. The inferior fronto-occipital fasciculus, anterior thalamic radiation, uncinate fasciculus, and external capsule were the most frequently associated pathways in both hemispheres.

    CONCLUSIONS: The Brain-Grid based classification system provides an accurate observational tool in all patients with suspected gliomas, based on the comparison of grid voxels on a morphological MRI and segmented white matter atlas. Important biological information on tumor kinetics including extension, speed, and preferential direction of progression can be observed and even predicted with this system. This novel classification can easily be applied to both prospective and retrospective cohorts of patients and increase our comprehension of glioma behavior.

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  • 11.
    Latini, Francesco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Berntsson, Shala G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    A novel radiological classification system for cerebral gliomas: The Brain-Grid.: Classification of cerebral gliomas with Brain-Grid system2019In: PLOS ONE, E-ISSN 1932-6203, Vol. 14, no 1, article id e0211243Article in journal (Refereed)
    Abstract [en]

    Purpose

    Standard radiological/topographical classifications of gliomas often do not reflect the real extension of the tumor within the lobar-cortical anatomy. Furthermore, these systems do not provide information on the relationship between tumor growth and the subcortical white mat- ter architecture. We propose the use of an anatomically standardized grid system (the Brain-Grid) to merge serial morphological magnetic resonance imaging (MRI) scans with a representative tractographic atlas. Two illustrative cases are presented to show the potential advantages of this classification system.

    Methods

    MRI scans of 39 patients (WHO grade II and III gliomas) were analyzed with a standardized grid created by intersecting longitudinal lines on the axial, sagittal, and coronal planes. The anatomical landmarks were chosen from an average brain, spatially normalized to the Mon- treal Neurological Institute (MNI) space and the Talairach space. Major white matter path- ways were reconstructed with a deterministic tracking algorithm on a reference atlas and analyzed using the Brain-Grid system.

    Results

    In all, 48 brain grid voxels (areas defined by 3 coordinates, axial (A), coronal (C), sagittal (S) and numbers from 1 to 4) were delineated in each MRI sequence and on the tractographic atlas. The number of grid voxels infiltrated was consistent, also in the MNI space. The sub- cortical insula/basal ganglia (A3-C2-S2) and the fronto-insular region (A3-C2-S1) were most frequently involved. The inferior fronto-occipital fasciculus, anterior thalamic radiation, unci- nate fasciculus, and external capsule were the most frequently associated pathways in both hemispheres.

    Conclusions

    The Brain-Grid based classification system provides an accurate observational tool in all patients with suspected gliomas, based on the comparison of grid voxels on a morphological MRI and segmented white matter atlas. Important biological information on tumor kinetics including extension, speed, and preferential direction of progression can be observed and even predicted with this system. This novel classification can easily be applied to both prospective and retrospective cohorts of patients and increase our comprehension of glioma behavior.

  • 12.
    Latini, Francesco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hesselager, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Differences in the preferential location and invasiveness of diffuse low-grade gliomas and their impact on outcome2020In: Cancer Medicine, E-ISSN 2045-7634, Vol. 9, no 15, p. 5446-5458Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Low-grade gliomas (LGGs) are primary diffuse slow-growing brain tumors derived from glial cells. The management of these tumors is dependent on their location, which often harbors eloquent areas. We retrospectively recorded the location of diffuse gliomas to identify whether specific differences exist between the histological types.

    METHODS: We analyzed 102 patients with previous histological diagnosis of WHO-II astrocytomas (62) and WHO-II oligodendrogliomas (40) according to WHO-2016 classification. MRI sequences (T2-FLAIR) were used for tumor volume segmentation and to create a frequency map of their locations within the Montreal Neurological Institute (MNI) space. The Brain-Grid (BG) system (standardized radiological tool of intersected lines according to anatomical landmarks) was created and merged with a tractography atlas for infiltration analysis.

    RESULTS: Astrocytomas frequently infiltrated association and projection white matter pathways within fronto-temporo-insular regions on the left side. Oligodendrogliomas infiltrated larger white matter networks (association-commissural-projection) of the frontal lobe bilaterally. A critical number of infiltrated BG voxels (7 for astrocytomas, 10 for oligodendrogliomas) significantly predicted shorter overall survival (OS) in both groups. Bilateral tumor extension in astrocytomas and preoperative tumor volume in oligodendrogliomas were independent prognostic factors for shorter OS.

    CONCLUSIONS: Astrocytomas and oligodendrogliomas differ in preferential location, and this has an impact on the type and the extent of white matter involvement. The number of BG voxels infiltrated reflected different tumor invasiveness and its impact on OS in both groups. All this new information may be valuable in neurosurgical oncology to classify and plan treatment for patients with diffuse gliomas.

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  • 13.
    Latini, Francesco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hjortberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Aldskogius, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Regenerative neurobiology.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    The Classical Pathways of Occipital Lobe Epileptic Propagation Revised in the Light of White Matter Dissection2015In: Behavioural Neurology, ISSN 0953-4180, E-ISSN 1875-8584, article id 872645Article in journal (Refereed)
    Abstract [en]

    The clinical evidences of variable epileptic propagation in occipital lobe epilepsy (OLE) have been demonstrated by several studies. However the exact localization of the epileptic focus sometimes represents a problem because of the rapid propagation to frontal, parietal, or temporal regions. Each white matter pathway close to the supposed initial focus can lead the propagation towards a specific direction, explaining the variable semiology of these rare epilepsy syndromes. Some new insights in occipital white matter anatomy are herein described by means of white matter dissection and compared to the classical epileptic patterns, mostly based on the central position of the primary visual cortex. The dissections showed a complex white matter architecture composed by vertical and longitudinal bundles, which are closely interconnected and segregated and are able to support specific high order functions with parallel bidirectional propagation of the electric signal. The same sublobar lesions may hyperactivate different white matter bundles reemphasizing the importance of the ictal semiology as a specific clinical demonstration of the subcortical networks recruited. Merging semiology, white matter anatomy, and electrophysiology may lead us to a better understanding of these complex syndromes and tailored therapeutic options based on individual white matter connectivity.

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  • 14.
    Latini, Francesco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hjortberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Aldskogius, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Regenerative neurobiology.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    The use of a cerebral perfusion and immersion-fixation process for subsequent white matter dissection2015In: Journal of Neuroscience Methods, ISSN 0165-0270, E-ISSN 1872-678X, Vol. 253, p. 161-169Article in journal (Refereed)
    Abstract [en]

    Background: The Klingler's method for white matter dissection revolutionized the study of deep cerebral anatomy. Although this technique made white matter dissection more feasible and widely used, it still presents some intrinsic limitations. New method: We evaluated the quality of different methods for specimen preparation based on an intra-carotidal formalin perfusion fixation process. Ten post-mortem human hemispheres were prepared with this method and dissected in a stepwise manner. Results: The homogeneous and rapid fixation of the brain allowed documentation of several fine additional anatomical details. Intra-cortical white matter terminations were described during the first stage of dissection on each specimen. No limitations were encountered during dissection of the major associative bundles. On the contrary, the quality of the fixation of the specimens made it possible to isolate them en bloc. One of the most complex and deep bundles (accumbo-frontal fasciculus) was dissected without technical limitations. Deep vascular structures were very well preserved and dissected within the white matter until their sub-millimetric terminations. Comparison with existing method: Short time for preparation, a more homogeneous fixation, no technical limitation for a detailed description of superficial and deep white matter anatomy, the possibility to dissect with a single technique the fibre organization and the white matter vascular architecture are the advantages reported with the perfusion fixation. Conclusion: These results provide encouraging data about the possibility to use a perfusion fixation process, which may help in improving the quality of white matter dissection for research, didactic purposes and surgical training.

  • 15.
    Latini, Francesco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Rapid and Accurate MRI Segmentation of Peritumoral Brain Edema in Meningiomas2017In: Clinical neuroradiology, ISSN 1869-1447, Vol. 27, no 2, p. 145-152Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    The extent of peritumoral brain edema (PTBE) in meningiomas commonly affects the clinical outcome. Despite its importance, edema volume is usually highly inaccurately approximated to a spheroid shape. We tested the accuracy and the reproducibility of semiautomatic lesion management software for the analysis of PTBE in a homogeneous case series of surgically confirmed intracranial meningiomas.

    METHODS:

    PTBE volume was calculated on magnetic resonance images in 50 patients with intracranial meningiomas using commercial lesion management software (Vue PACS Livewire, Carestream, Rochester, NY, USA). Inter and intraobserver agreement evaluation and a comparison between manual volume calculation, the semiautomatic software and spheroid approximation were performed in 22 randomly selected patients.

    RESULTS:

    The calculation of edema volume was possible in all cases irrespective of the extent of the signal changes. The median time for each calculation was 3 min. Interobserver and intraobserver agreement confirmed the reproducibility of the method. Comparison with standard (fully manual) calculation confirmed the accuracy of this software.

    CONCLUSIONS:

    Our study showed a high level of reproducibility of this semiautomatic computational method for peritumoral brain edema. It is rapid and easy to use after relatively short training and is suitable for implementation in clinical practice.

  • 16.
    Latini, Francesco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Mårtensson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fredriksson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Hjortberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Aldskogius, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Regenerative neurobiology.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Segmentation of the inferior longitudinal fasciculus in the human brain: A white matter dissection and diffusion tensor tractography study.2017In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, no 1675, p. 102-115, article id S0006-8993(17)30386-4Article in journal (Refereed)
    Abstract [en]

    The inferior longitudinal fascicle (ILF) is one of the major occipital-temporal association pathways. Several studies have mapped its hierarchical segmentation to specific functions. There is, however, no consensus regarding a detailed description of ILF fibre organisation. The aim of this study was to establish whether the ILF has a constant number of subcomponents. A secondary aim was to determine the quantitative diffusion proprieties of each subcomponent and assess their anatomical trajectories and connectivity patterns. A white matter dissection of 14 post-mortem normal human hemispheres was conducted to define the course of the ILF and its subcomponents. These anatomical results were then investigated in 24 right-handed, healthy volunteers using in vivo diffusion tensor imaging (DTI) and streamline tractography. Fractional anisotropy (FA), volume, fibre length and the symmetry coefficient of each fibre group were analysed. In order to show the connectivity pattern of the ILF, we also conducted an analysis of the cortical terminations of each segment. We confirmed that the main structure of the ILF is composed of three constant components reflecting the occipital terminations: the fusiform, the lingual and the dorsolateral-occipital. ILF volume was significantly lateralised to the right. The examined indices of ILF subcomponents did not show any significant difference in lateralisation. The connectivity pattern and the quantitative distribution of ILF subcomponents suggest a pivotal role for this bundle in integrating information from highly specialised modular visual areas with activity in anterior temporal territory, which has been previously shown to be important for memory and emotions.

  • 17.
    Latini, Francesco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Rethinking the standard trans-cortical approaches in the light of superficial white matter anatomy2015In: Neural Regeneration Research, ISSN 1673-5374, E-ISSN 1876-7958, Vol. 10, no 12, p. 1906-1909Article, review/survey (Refereed)
    Abstract [en]

    A better comprehension of the superficial white matter organization is important in order to minimize potential and avoidable damage to long or intermediate association fibre bundles during every step of a surgical approach. We recently proposed a technique for cadaver specimen preparation, which seems able to identify a more systematic organization of the superficial white matter terminations. Moreover, the use of the physiological intracranial vascular network for the fixation process allowed us to constantly show main vascular landmarks associated with white matter structures. Hence three examples of standard approaches to eloquent areas are herein reanalyzed starting from the first superficial layer. New insights into the possible surgical trajectories and subsequent quantitative damages of both vessels and white matter fibres can help readapt even the most standard and widely accepted approach trough the brain cortex. A more detailed study of these fine anatomical details may become in the near future a fundamental part of the neurosurgical training and the preoperative planning.

  • 18.
    Latini, Francesco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Teaching Anatomy to Neuroscientific Health-Care Professionals: Are They Receiving the Best Anatomical Education?2020In: Medical Science Educator, E-ISSN 2156-8650, Vol. 30, no 1, p. 41-45Article in journal (Refereed)
    Abstract [en]

    University neuroanatomical courses seldom teach the anatomical-functional connectivity of the brain. White matter dissection improves understanding of brain connectivity, but until now has been restricted to neurosurgeons and in some cases to medical students, never to health-care non-medical professionals. Our aim was to teach white matter anatomy to medical and non-medical students to evaluate this technique in groups with different education. A standardized lab demonstration of white matter anatomy was performed with high appreciation rate in both groups, suggesting a suboptimal neuroanatomical education provided by basic course. We encourage to include this technique of teaching brain anatomy into basic neuroanatomical courses to improve the level of comprehension and competence in all health-care staff within the field of neuroscience.

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  • 19.
    Latini, Francesco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Trevisi, Gianluca
    Osped Santo Spirito, Dept Surg, Neurosurg Unit, Pescara, Italy.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Jemstedt, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Speech-Language Pathology.
    Alberius Munkhammar, Åsa
    Uppsala Univ Hosp, Rehabil & Pain Ctr, Uppsala, Sweden.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Hesselager, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    New Insights Into the Anatomy, Connectivity and Clinical Implications of the Middle Longitudinal Fasciculus2021In: Frontiers in Neuroanatomy, E-ISSN 1662-5129, Vol. 14, article id 610324Article in journal (Refereed)
    Abstract [en]

    The middle longitudinal fascicle (MdLF) is a long, associative white matter tract connecting the superior temporal gyrus (STG) with the parietal and occipital lobe. Previous studies show different cortical terminations, and a possible segmentation pattern of the tract. In this study, we performed a post-mortem white matter dissection of 12 human hemispheres and an in vivo deterministic fiber tracking of 24 subjects acquired from the Human Connectome Project to establish whether a constant organization of fibers exists among the MdLF subcomponents and to acquire anatomical information on each subcomponent. Moreover, two clinical cases of brain tumors impinged on MdLF territories are reported to further discuss the anatomical results in light of previously published data on the functional involvement of this bundle. The main finding is that the MdLF is consistently organized into two layers: an antero-ventral segment (aMdLF) connecting the anterior STG (including temporal pole and planum polare) and the extrastriate lateral occipital cortex, and a posterior-dorsal segment (pMdLF) connecting the posterior STG, anterior transverse temporal gyrus and planum temporale with the superior parietal lobule and lateral occipital cortex. The anatomical connectivity pattern and quantitative differences between the MdLF subcomponents along with the clinical cases reported in this paper support the role of MdLF in high-order functions related to acoustic information. We suggest that pMdLF may contribute to the learning process associated with verbal-auditory stimuli, especially on left side, while aMdLF may play a role in processing/retrieving auditory information already consolidated within the temporal lobe.

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  • 20.
    Lönnemark, Olle
    et al.
    Section of Neurosurgery, Department of Neuroscience, Uppsala University Hospital, Uppsala, Sweden.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Sundblom, Jimmy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Cranioplasty in Brain Tumor Surgery: A Single-Center Retrospective Study Investigating Cranioplasty Failure and Tumor Recurrence2023In: World Neurosurgery, ISSN 1878-8750, E-ISSN 1878-8769, Vol. 170, p. e313-e323Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Cranioplasty with synthetic implant can be performed to restore function and form of the skull after resection of malignancy infiltrating the bone. The aim of this study was to examine the rate of implant failure and tumor recurrence in patients undergoing nonautologous cranioplasty and tumor resection.

    METHODS: In this retrospective single-center study, 48 patients were identified who had undergone cranioplasty with synthetic implants after tumor resection between 2010 and 2020. The medical records were analyzed to investigate patient demographics, surgery data, cranioplasty failure rates, and rate of tumor recurrence.

    RESULTS: Cranioplasty failed in 8 patients. The median time to implant failure was 220 days with most failures occurring within 1 year (5 of 8). There was no significant difference in rate or time to failure between the different cranioplasty materials (P = 0.39). Low body mass index (P < 0.05), previous craniectomy/cranioplasty (P < 0.05), previous radiation therapy to the brain/skull (P < 0.05), and skin closure with sutures (P < 0.05) were associated with an increased risk of implant failure. Tumors recurred in 15 patients.

    CONCLUSIONS: Cranioplasty surgery with synthetic implants carries a relatively high risk of failure, regardless of type of cranioplasty material used. Skin closure with staples may be beneficial in these patients.

  • 21.
    Neves, Inês
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Lu, Xi
    Maturi, Nagaprathyusha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neurooncology and neurodegeneration.
    Dang, Yonglong
    Latini, Francesco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Yildirim, Irem
    Sundström, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergström, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neurooncology and neurodegeneration.
    Jokinen, Veera
    Xing, Pengwei
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular Tools and Functional Genomics.
    Jarvius, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Fryknäs, Mårten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Chen, Xingqi
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular Tools and Functional Genomics.
    Swartling, Fredrik J.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neurooncology and neurodegeneration.
    Uhrbom, Lene
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neurooncology and neurodegeneration.
    Paired glioblastoma cell cultures of the fluorescent bulk tumor and non-fluorescent tumor margin display differential phenotypes and cell states across patientsManuscript (preprint) (Other academic)
    Abstract [en]

    Glioblastoma is an aggressive and therapy-resistant primary brain tumor with a dismal prognosis. The inevitable recurrence is in almost all patients in contact with the resection cavity, suggesting the local peritumoral area as its origin. Glioblastoma cells of this region have seldom been studied and few authenticated models exist. We have explanted matched tissue samples from the bulk tumor and local tumor edge of 13 glioblastoma patients of which 7 were sustainable beyond passage 6. Each edge culture was more invasive and less self-renewing and tumorigenic compared to its paired bulk culture. Three pairs of edge and bulk cultures were profiled with a combined single nucleus (sn) RNA- and ATAC-sequencing. Transcriptome analysis displayed for all patients a shift towards AC-MES cell states in the edge cultures. Chromatin-accessibility profiles uncovered differential regulatory networks with edge cells being enriched for transcription factor (TF) motifs of invasion, neurons, and immune cells. We propose that edge cells have been epigenetically reprogrammed by their unique interactions with various cell types in the peritumoral region. The fact that glioblastoma edge cells display distinct epigenetic regulation compared to their bulk tumor cells has implications for therapy development that should be targeted to and tested on the relapse-causing glioblastoma edge cells.

  • 22. Norbäck, Ola
    et al.
    Gál, Gyula
    Johansson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Solander, Sten
    Tovi, Metin
    Persson, Lennart
    Ronne-Engström, Elisabeth
    Enblad, Per
    The establishment of endovascular aneurysm coiling at a neurovascular unit: report of experience during early years.2005In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 47, no 2Article in journal (Refereed)
    Abstract [en]

    The treatment of cerebral aneurysms is changing from surgical clipping to endovascular coiling (EVC) in many neurovascular centres. The aim of this study was to evaluate the technical results and clinical outcome at 6 months in a consecutive series of subarachnoid hemorrhage (SAH) patients treated with EVC, in a situation when the EVC had been established very rapidly as the first line of treatment at a neurovascular centre. The patient material comprised 239 SAH patients (155 women and 84 men, mean age 55 years, age range 16-81) allocated to EVC as the first line of treatment in the acute stage (within 3 weeks of rupture) between September 1996 and December 2000. Clinical grade on admission was Hunt & Hess (H&H) I and II in 42%, H&H III in 25% and H&H grade IV and V in 33% of the patients. The aneurysm was located in the anterior circulation in 82% of the cases. EVC was performed on days 0-3 in 77% of the cases. EVC of the target aneurysm was able to be completed in 222 patients (93%). Complete occlusion was achieved in 126 patients (53%). Procedural complications occurred in 39 patients (16%). Favourable clinical outcome was observed in 57%, severe disability in 28% and poor outcome in 14% of the patients. Favourable outcome was achieved in 77% of H&H I and II patients and in 43% of H&H III-V patients. The multivariate logistic regression analysis revealed that younger age, good neurological grade on admission, absence of intracerebral hematoma and intraventricular hematoma respectively, ICA-PcomA aneurysm location, later treatment and absence of complications were significant predictors of favourable outcome. After interventional training and installation of the X-ray system, the introduction and establishment of EVC at a neurovascular unit can be done in a short period of time and with favourable results. Future studies must concentrate on identifying factors of importance for the choice of interventional or surgical therapy. The results of this study indicate that endovascular therapy may be particularly beneficial in poor-grade patients and in patients with aneurysms in the ICA-PcomA territory.

  • 23.
    Ronne-Engström, Elisabeth
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Gál, Gyula
    Norbäck, Ola
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Cesarini, Kristina Giuliana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Bolander, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Tovi, Metin
    Persson, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Patients with spontaneous subarachnoid haemorrhage: presentation of a 10-year hospital series2009In: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 23, no 5, p. 499-506Article in journal (Refereed)
    Abstract [en]

    In this study we present the population-based patient material with spontaneous SAH, treated in our Neurosurgical unit during the 10 years (1997-2006) after the introduction of endovascular treatment of aneurysms (EVT) in our hospital. All patients that had a spontaneous SAH and a potential to survive were admitted. The present study comprises 1471 patients. 72 % had one or more aneurysms. AVM or other vascular pathological findings where found in 2%. Angiography was judged as normal in 21% and was not performed in 5%. 664 of the patients with aneurysms were treated by endovascular means, 333 were operated and 31 were treated with both methods. Thirty-five received no treatment. The main difference in admission parameters between the coiled and clipped aneurysms was the location of the aneurysm, with posterior circulation aneurysm exclusively being coiled and MCA aneurysms mainly clipped. The highest 6-month mortality for aneurysms presented in the untreated group (71.4%), and the lowest (3.2%) in the group treated with both clip and coil. Six-month mortality was 3.5% for the patients with a normal angiography. Of these, no one with Fisher grade 1 and 2/120 patients with Fisher 2 died. The mortality was high (89%) for those patients where angiography was not performed. The present patient group was compared to an earlier published a 12-year patient series from our clinic. The patients with aneurysmal SAH in the present series were older and had a lower 6-month mortality in our material compared to the published data from our clinic from 1981-1992. More patients were admitted in a good clinical condition in the present series, but there was also a higher proportion of patients from the worst clinical groups. The percentage of aneurysms treated had increased from 80% to 97% after EVT was introduced.

  • 24.
    Ryttlefors, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Latini, Francesco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Montelius, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Gudjonsson, Olafur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Long-term evaluation of the effect of hypofractionated high-energy proton treatment of benign meningiomas by means of (11)C-L-methionine positron emission tomography2016In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, no 8, p. 1432-1443Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To determine if (11)C-L-methionine PET is a useful tool in the evaluation of the long-term effect of proton beam treatment in patients with meningioma remnant.

    METHODS: Included in the study were 19 patients (4 men, 15 women) with intracranial meningioma remnants who received hypofractionated high-energy proton beam treatment. Patients were examined with (11)C-L-methionine PET and MRI prior to treatment and after 6 months, and 1, 2, 3, 5, 7 and 10 years. Temporal changes in methionine uptake ratio, meningioma volume, meningioma regrowth and clinical symptoms throughout the follow-up period were evaluated.

    RESULTS: In 17 patients the tumour volume was unchanged throughout the follow-up. The methionine uptake ratio on PET decreased over the years in most patients. In two patients the tumour remnant showed progression on MRI. In these patients, prior to the volume increase on MRI, the methionine uptake ratio increased. One patient experienced transient clinical symptoms and showed radiological evidence of a radiation-induced reaction close to the irradiated field.

    CONCLUSION: Proton beam treatment is a safe and effective treatment for achieving long-term growth arrest in meningioma remnants. Follow-up with (11)C-L-methionine PET may be a valuable adjunct to, but not a replacement for, standard radiological follow-up.

  • 25.
    Ryttlefors, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Kerr, Richard S.C.
    Nuffield Dept Surgery, Radcliff, University of Oxford, UK.
    Molyneux, Andrew J.
    Neurovasc Res Unit, Radcliff, University of Oxford, UK.
    International Subarachnoid Aneurysm Trial of neurosurgical clipping versus endovascular coiling: Subgroup analysis of 278 elderly patients2008In: Stroke, Vol. 39, no 10, p. 2720-2726Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: It is often thought that elderly patients in particular would benefit from endovascular aneurysm treatment. The aim of this analysis was therefore to compare the efficacy and safety of endovascular coiling (EVT) with neurosurgical clipping (NST) in the subgroup of elderly SAH patients in the International Subarachnoid Aneurysm Trial (ISAT). METHODS: In the ISAT cohort 278 SAH patients, 65 years or older, were enrolled. The patients were randomly allocated EVT (n=138) or NST (n=140). The primary outcome was the proportion of patients with a modified Rankin scale score of 0 to 2 (independent survival) at 1 year after the SAH. The rates of procedural complications and adverse events were also recorded. RESULTS: 83 of 138 (60.1%) patients allocated EVT were independent compared to 78 of 140 (56.1%) allocated NST (N.S.). 36 of 50 (72.0%) patients with internal carotid and posterior communicating artery aneurysms allocated EVT were independent compared to 26 of 50 (52.0%) allocated NST (P<0.05). 10 of 22 (45.5%) patients with middle cerebral artery aneurysms allocated EVT were independent compared to 13 of 15 (86.7%) allocated NST (P<0.05). The epilepsy frequency was 0.7% in the EVT group compared to 12.9% in the NST group (P<0.001). CONCLUSIONS: In good grade elderly SAH patients with small anterior circulation aneurysms, EVT should probably be the favored treatment for ruptured internal carotid and posterior communicating artery aneurysms, whereas elderly patients with ruptured middle cerebral artery aneurysms appear to benefit from NST. EVT resulted in a lower epilepsy frequency than NST.

  • 26.
    Ryttlefors, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Persson, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ilodigwe, Don
    Macdonald, R. Loch
    Patient age and vasospasm after subarachnoid hemorrhage2010In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 67, no 4, p. 911-917Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Subarachnoid hemorrhage (SAH) from a ruptured intracranial aneurysm is a devastating disease with high mortality and morbidity. The incidence of SAH increases with advancing age. OBJECTIVE: To determine whether age is an independent predictor of angiographic vasospasm, delayed ischemic neurological deficits (DINDs), or abnormal transcranial Doppler (TCD) measurements in patients with aneurysmal subarachnoid hemorrhage. METHODS: Data from CONSCIOUS-1 (Clazosentan to Overcome Neurological Ischemia and Infarct Occurring After Subarachnoid Hemorrhage study), a dose-finding study of clazosentan, were used. Data on angiographic vasospasm, DINDs, and TCD abnormalities were prospectively recorded as well as baseline characteristics and treatment data. Patient age was considered in 3 ways: as a continuous variable, dichotomized at age 65 years, and categorized by decade. Age was investigated as the main variable, whereas other possible confounding variables were adjusted for in the multiple logistic regression modeling with each of 3 dichotomized vasospasm outcome measures, presence or absence of angiographic vasospasm, DINDs, and TCD abnormalities as the dependent variable. RESULTS: The proportions of patients with angiographic vasospasm, DINDs, and TCD abnormalities were 45%, 19%, and 81%, respectively. Age, whether considered as a continuous, dichotomous, or a categorical variable, was not significantly associated with angiographic vasospasm, DINDs, or abnormal TCD measurements. CONCLUSION: Age does not seem to be a significant predictor for cerebral vasospasm after subarachnoid hemorrhage.

  • 27.
    Ryttlefors, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Howells, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Secondary insults in subarachnoid hemorrhage: occurrence and impact on outcome and clinical deterioration2007In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 61, no 4, p. 704-714Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study the occurrence of secondary insults during neurointensive care of patients with subarachnoid hemorrhage using a computerized multimodality monitoring system and to study the impact of secondary insults on clinical deterioration and functional outcome.

    METHODS: Patients with subarachnoid hemorrhage who were admitted to the neurointensive care unit between January 1999 and December 2002 with at least 120 hours of multimodality monitoring data within the first 240 hours of neurointensive care were included. Data were continuously recorded for intracranial pressure (ICP), cerebral perfusion pressure (CPP), mean arterial blood pressure, systolic blood pressure, oxygen saturation, and temperature. Secondary insult levels were defined as ICP of 20 or greater or 25 or greater; CPP of 60 or lower, 55 or lower, greater than 100, or greater than 110; mean arterial blood pressure of 80 or lower, 70 or lower, 120 or greater, or 130 or greater; systolic blood pressure of 110 or lower, 100 or lower, 180 or greater, or 200 or greater; temperature of 38°C or higher or 39°C or higher; and oxygen saturation of less than 95 or less than 90. Secondary insults were quantified as the proportion of good monitoring time at the insult level. Uni- and multivariate logistic regression analyses were performed with admission and secondary insult variables as explanatory variables and clinical deterioration and independent outcome as the dependent variable, respectively.

    RESULTS: Ninety-nine patients (67 women; mean age, 57.8 yr) met the inclusion criteria. In the univariate analysis, ICP of 20 or greater, ICP of 25 or greater, CPP of 60 or less, and CPP of 55 or less increased the risk of clinical deterioration, whereas CPP greater than 100 and systolic blood pressure greater than 180 decreased the risk of clinical deterioration. In the multivariate logistic regression, ICP of 25 or greater and CPP of greater than 100 had an independent effect on clinical deterioration. The occurrence of secondary insults had no significant effect on functional outcome.

    CONCLUSION: Elevated ICP not responding to treatment is predictive of clinical deterioration, whereas high CPP decreases the risk of clinical deterioration. It may be beneficial to not lower spontaneous high CPP in patients with subarachnoid hemorrhage.

  • 28.
    Ryttlefors, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Howells, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Neurointensive care is justified in elderly patients with severe subarachnoid hemorrhage--an outcome and secondary insults study2010In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 152, no 2, p. 241-249Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim was to study the outcome and the occurrence of secondary brain insults in elderly patients with severe subarachnoid hemorrhage (SAH) in comparison to younger patients. METHODS: Ninety-nine patients with severe SAH requiring a ventriculostomy and management at the neurointensive care unit with at least 120 h of multimodality monitoring data during the first 240 h following SAH were included. Data were continuously recorded for intracranial pressure (ICP), cerebral perfusion pressure, blood pressure, oxygen saturation, and temperature. Secondary insult levels were defined and quantified as percent of good monitoring time at insult level. Outcome according to the Glasgow Outcome Scale was evaluated at 6 months after the SAH. Age-dependent differences in occurrence of secondary insults and clinical characteristics were analyzed with multiple regression analysis. RESULTS: Good recovery or moderate disability was achieved in 24.1% of the elderly and in 42.9% of the younger patients. The frequency of severe disability was 41.4% in the elderly and 37.1% in the younger patients. The occurrence of ICP insults was lower and the occurrence of hypertensive, hypotensive, and hypoxemic insults were higher in the elderly patients. CONCLUSIONS: An independent outcome was achieved in a substantial proportion of the elderly with severe SAH, and the proportion of severe disability was not greater than among the younger patients, which justifies neurointensive care also in elderly patients. The occurrence of secondary insults was age dependent. Future studies of multimodality monitoring may provide age-specific secondary insult levels necessary for a tailored neurointensive care specific for elderly patients with severe SAH.

  • 29.
    Ryttlefors, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Latini, Francesco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Basma, Jaafar
    Krisht, Ali F
    Intraoperative Intratumoral Embolization of a Complex Recurrent Hemangiopericytoma: Technical Report and Review of the Literature2016In: Central European Neurosurgery, ISSN 2193-6315, E-ISSN 2193-6323, Vol. 77, no 4, p. 361-366Article, review/survey (Refereed)
    Abstract [en]

    Objective Recurrent brain tumors represent a challenge for neurosurgeons because of the extensive blood loss and the time needed for surgical resection. Only a few hemostatic agents are useful to prevent the bleeding and thus facilitate the surgical resection. Fibrin sealant can be used to achieve sealing, tissue adherence, or hemostasis when other means of hemostasis are inadequate or inappropriate. We report the feasibility and positive effects of direct intratumoral injection of fibrin sealant during resection of a recurrent hemangiopericytoma. Material and Methods The intraoperative intratumoral injection of fibrin sealant changed the tumor properties of a recurrent hemangiopericytoma of the tentorium with infra- and supratentorial extension. From a loose friable briskly bleeding tumor, this complex lesion became a nonbleeding well-demarcated soft-firm tumor that could easily be dissected off the pial surface and totally resected without extensive bleeding. Results There are several benefits of intratumoral injection of fibrin sealant in hemangiopericytomas: (1) the extensive bleeding is diminished and blood loss minimized; (2) the restriction of the surgical view by the venous oozing is diminished, making the microsurgical dissection of the tumor capsule off the pial surface easier and safer; (3) the loose consistency of the tumor becomes firmer and facilitates the manipulation of the tumor and leads to a safer resection; and (4) a shorter operating time is needed. Conclusion The use of intratumoral fibrin glue injection is a safe and useful technique that could be used for hemostasis of highly vascularized tumors to facilitate a safer resection and to reduce blood loss.

  • 30.
    Samuelsson, Carolina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hesselager, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Salci, Konstantin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Cerebral glutamine and glutamate levels in relation to compromised energy metabolism: a microdialysis study in subarachnoid hemorrhage patients2007In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 27, no 7, p. 1309-1317Article in journal (Refereed)
    Abstract [en]

    Astrocytic glutamate (Glt) uptake keeps brain interstitial Glt levels low. Within the astrocytes Glt is converted to glutamine (Gln), which is released and reconverted to Glt in neurons. The Glt–Gln cycle is energy demanding and impaired energy metabolism has been suggested to cause low interstitial Gln/Glt ratios. Using microdialysis (MD) measurements from visually noninjured cortex in 33 neurointensive care patients with subarachnoid hemorrhage, we have determined how interstitial Glt and Gln, as a reflection of the Glt–Gln cycle turnover, relate to perturbed energy metabolism. A total of 3703 hourly samples were analyzed. The lactate/pyruvate (L/P) ratios correlated to the Gln/Glt ratios (r=-0.66), but this correlation was not stronger than the correlation between L/P and Glt (r=0.68) or the correlation between lactate and Glt (r=0.65). A novel observation was a linear relationship between interstitial pyruvate and Gln (r=0.52). There were 13 periods (404 h) of 'energy crisis', defined by L/P ratios above 40. All were associated with high interstitial Glt levels. Periods with L/P ratios above 40 and low pyruvate levels were associated with decreased interstitial Gln levels, suggesting ischemia and failing astrocytic Gln synthesis. Periods with L/P ratios above 40 and normal or high pyruvate levels were associated with increased interstitial Gln levels, which may represent an astrocytic hyperglycolytic response to high interstitial Glt levels. The results imply that moderately elevated L/P ratios cannot always be interpreted as failing energy metabolism and that interstitial pyruvate levels may discriminate whether or not there is sufficient astrocytic capacity for Glt–Gln cycling in the brain.

  • 31.
    Sundblom, Jimmy
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nowinski, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Casar Borota, Olivera
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Removal of giant intraosseous meningioma followed by cranioplasty using a custom-made bioceramic implant: case report2019In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 131, no 3, p. 735-739Article in journal (Refereed)
    Abstract [en]

    Intraosseous meningioma of the chordoid type is a rare clinical entity. Radical surgical removal and subsequent cranioplasty is the treatment of choice. Here, the authors report a severe case involving more than 70% of the calvarial surface area, which was removed and repaired using a prefabricated custom-made, titanium-reinforced, bioceramic implant and bone-cutting guides. Tumor removal and good esthetic outcome were achieved, along with a 17.1% increase of intracranial volume. Bioceramic implants have shown promising initial results and may represent an important new tool in the surgeon's armamentarium.

  • 32.
    Sundblom, Jimmy
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Xheka, Fabjola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Clinical Pathology, Uppsala University Hospital.
    Casar Borota, Olivera
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Clinical Pathology, Uppsala University Hospital.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Bone formation in custom-made cranioplasty: evidence of early and sustained bone development in bioceramic calcium phosphate implants. Patient series2021In: Journal of Neurosurgery: Case Lessons, E-ISSN 2694-1902, Vol. 1, no 17Article in journal (Refereed)
    Abstract [en]

    BACKGROUND

    Implant failure (IF) rates in cranioplasty remain high despite efforts to reduce the incidence. New biomaterials may be part of the solution for this problem. Formation of autologous bone in implants may reduce rates of infection and subsequent failure.

    OBSERVATIONS

    Four patients with calcium phosphate implants supported by titanium mesh and undergoing surgery for reasons unrelated to IF were included in this series. Samples from the implants were microscopically examined. Pathological studies proved the formation of autologous bone in the calcium phosphate implants.

    LESSONS

    Bone and blood vessel formation in the implants and diminished foreign body reaction to autologous bone may reduce the rates of IF.

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  • 33.
    Svedung-Wettervik, Teodor
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Enblad: Neurosurgery.
    Ersson, Marcus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Enblad: Neurosurgery.
    Latini, Francesco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Enblad: Neurosurgery.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Enblad: Neurosurgery.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Enblad: Neurosurgery.
    Patient-reported quality of life in grade 2 and 3 gliomas after surgery, can we do more?2022In: Clinical neurology and neurosurgery, ISSN 0303-8467, E-ISSN 1872-6968, Vol. 214, article id 107175Article in journal (Refereed)
    Abstract [en]

    Objective: To study the effects of surgery and the explanatory variables for patient-reported health-related quality of life (HRQoL) after brain tumor surgery for astrocytomas and oligodendrogliomas grade 2 and 3.

    Methods: Patients operated for an astrocytoma or an oligodendrogliomas, grade 2 or 3, at the Department of Neurosurgery, Uppsala, Sweden, 2016-2021, were included. HRQoL was assessed with RAND-36 preoperatively and 4 months postoperatively. Demographic, tumor, and treatment data were prospectively collected.

    Results: Sixty-two patients were included, 34 with an astrocytoma and 28 with an oligodendroglioma. Physical function, role physical, general health, vitality, and social functioning decreased significantly (p-values < 0.01) 4 months after surgery, whereas bodily pain, role emotional, and mental health remained unchanged. In Spearman analyses, younger patients deteriorated more in role physical, females worsened less often in general health but more often in social functioning than males, a higher level of education correlated with a more pronounced drop in social functioning, and a greater extent of resection corresponded to a worsening in physical function postoperatively (p-values < 0.05).

    Conclusions: Several HRQoL domains deteriorated after glioma surgery in specific groups of patients, particularly general health, vitality, physical, and social functions. This was only weakly explained by surgical variables. Specific groups of patients may need closer follow-ups and tailored support/rehabilitation to detect and address these HRQoL deteriorations.

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  • 34.
    Svedung-Wettervik, Teodor
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Munkhammar, Åsa A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Jemstedt, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Ersson, Marcus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Latini, Francesco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Dynamics in cognition and health-related quality of life in grade 2 and 3 gliomas after surgery2022In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 164, no 12, p. 3275-3284Article in journal (Refereed)
    Abstract [en]

    Background

    The focus of clinical management and research in gliomas has been on survival, but the interest in the treatment effects on cognition and health-related quality of life (HRQoL) is emerging. The primary aim of this study was to investigate the dynamics in cognition after brain tumor surgery for astrocytomas and oligodendrogliomas grade 2 and 3. The secondary aim was to investigate the association of postoperative changes in cognition with changes HRQoL.

    Methods

    In this observational study, 48 patients operated for an astrocytoma or oligodendrogliomas, grade 2 or 3, at the Department of Neurosurgery, Uppsala, Sweden, 2016–2021, were included. Cognitive and language skills were assessed with a selected test battery and HRQoL was patient-reported as assessed with RAND-36 pre- and approximately 3 months postoperatively.

    Results

    There was a significant postoperative decrease in attention span and verbal learning, but the patients improved in the test for visual memory. There was no change in visual attention, executive function, verbal memory, visual organization and construction, verbal fluency, and confrontation naming. The RAND-36 variables physical function, role physical, general health, vitality, and social functioning decreased significantly after surgery. Patients operated for tumor recurrence exhibited greater deterioration in attention and a greater extent of resection correlated with a less pronounced decrease in verbal memory, but there were otherwise weak associations between the dynamics in cognition and patient-, tumor-, and treatment-variables. A decline in cognitive variables was not associated with worse HRQoL.

    Conclusions

    Although both several cognitive and HRQoL domains deteriorated postoperatively, these changes did not correlate with each other. This highlights the complexity of cognitive and HRQoL dynamics in the early postoperative phase.

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  • 35.
    Uche, E. O.
    et al.
    Univ Nigeria, Fac Med Sci, Neurosurg Unit, Teaching Hosp Ituku Ozalla, Enugu, Ituku, Nigeria.;Univ Nigeria, Coll Med, Fac Med Sci, Neurosurg Unit, Enugu 40001, Ituku, Nigeria..
    Sundblom, Jimmy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Uko, Uko Kalu
    Univ Nigeria, Fac Med Sci, Neurosurg Unit, Teaching Hosp Ituku Ozalla, Enugu, Ituku, Nigeria..
    Kamalo, Patrick
    Blantyre Inst Neurol Sci, Dept Neurosurg, Blantyre, Malawi..
    Doe, Alvin Nah
    John F Kennedy Mem Hosp, Dept Surg, Neurosurg Unit, Monrovia, Liberia..
    Eriksson, Linn
    Karolinska Univ Hosp, Perioperat Med & Intens Care PMI, Stockholm, Sweden..
    Sandvik, Ulrika
    Karolinska Univ Hosp, Karolinska Inst, Dept Neurosurg Clin Neurosci, Stockholm, Sweden..
    Revesz, David F.
    Uppsala Univ Hosp, Dept Neurosurg, S-75185 Uppsala, Sweden..
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Tisell, Magnus
    Sahlgrens Univ Hosp, Dept Neurosurg, S-1345 Gothenburg, Sweden..
    Global neurosurgery over a 60-year period: Conceptual foundations, time reference, emerging Co-ordinates and prospects for collaborative interventions in low and middle income countries2022In: BRAIN AND SPINE, ISSN 2772-5294, Vol. 2, article id 101187Article in journal (Refereed)
    Abstract [en]

    Introduction: We evaluated salient initiatives invested in global neurosurgery over a 60-year period.

    Research question: What are the Phases, Achievements, Challenges, and Lessons of Global Neurosurgery.

    Methods: A 60-year retrospective study from 1960 to 2020 analyzing the major phases, lessons, and progress notes. We reviewed the foundational need questions and innovated tools used to answer them.

    Results: Three phases defining our study period were identified. In the early phase, birthing academic units and the onset of individual volunteerism were dominant concepts. The 2nd phase is summarized by the rise of volunteerism and surgical camps. The third phase is heralded by advocacy and strategies for achieving care equity.The defining moment is the Lancet commission for global surgery summit in 2015. Lessons include the need for evaluation of the resources of recipient and donor locations using novel global surgery tools.

    Conclusion: Global neurosurgery over the 60-year study period is summarized by indelible touchstones of personal and group efforts as well as triumphs derived from innovations in the face of formidable challenges.

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  • 36.
    Uche, Enoch O.
    et al.
    Univ Nigeria, Neurosurg Unit, Dept Surg, Ituku Ozalla Campus, Enugu, Nigeria.;Univ Nigeria, Teaching Hosp, Ituku Ozalla Enugu 40001, Nigeria..
    Mezue, Wilfred C.
    Univ Nigeria, Neurosurg Unit, Dept Surg, Ituku Ozalla Campus, Enugu, Nigeria..
    Ajuzieogu, Obinna
    Univ Nigeria, Dept Anaesthesia, Ituku Ozalla Campus, Enugu, Nigeria..
    Amah, Christopher C.
    Univ Nigeria, Teaching Hosp, Ituku Ozalla Enugu 40001, Nigeria..
    Onyia, Ephraim
    Univ Nigeria, Neurosurg Unit, Dept Surg, Ituku Ozalla Campus, Enugu, Nigeria..
    Iloabachie, Izuchukwu
    Univ Nigeria, Neurosurg Unit, Dept Surg, Ituku Ozalla Campus, Enugu, Nigeria..
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Tisell, Magnus
    Sahlgrens Univ Hosp, Dept Neurosurg, S-41345 Gothenburg, Sweden..
    Improving capacity and access to neurosurgery in sub-Saharan Africa using a twinning paradigm pioneered by the Swedish African Neurosurgical Collaboration2020In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 162, no 5, p. 973-981Article in journal (Refereed)
    Abstract [en]

    Background

    The unmet need for neurosurgery in sub-Saharan Africa is staggering. Resolving this requires strategies that synergize salient local resources with tailored foreign help. This study is a trial of a twinning model adopted by the Swedish African Neurosurgical Collaboration (SANC).

    Methods

    A multi-step neurosurgical twinning technique, International Neurosurgical Twinning Modeled for Africa (INTIMA), developed through a collaboration between African and Swedish neurosurgical teams was adopted for a neurosurgical mission in March 2019. The pioneering steps are evaluated together with data of treated patients prospectively acquired using SPSS Chicago Inc., Version 23. Associations were analyzed using chi-square tests, while inferences were evaluated at 95% level of significance.

    Results

    The SANC global neurosurgery mission targeted microsurgical brain tumor resection. Fifty-five patients were operated on during the mission and subsequent 3 months. Patients’ ages ranged from 3 months to 69 years with a mean of 30.6 ± 2.1 years 95% CL. Seven cases were performed during the first mission, while 48 were performed after the mission. Compared to 3 months before SANC when only 9 brain tumors were resected, more tumors were resected (n = 25) within the 3 consecutive months from the mission (X2 = 14.2, DF = 1, P = 0.000). Thirty-day mortality following tumor resection was also lower, X2 = 4.8, DF = 1, P = 0.028.

    Conclusion

    Improvements in capacity and short-term outcome define our initial pioneering application of a neurosurgical twinning paradigm pioneered by SANC.

  • 37.
    Uche, Enoch Ogbonnaya
    et al.
    Univ Nigeria, Div Neurosurg, Ituku Ozalla Campus, Enugu, Nigeria..
    Eke, Christopher B.
    Univ Nigeria, Dept Pediat, Ituku Ozalla Campus, Enugu, Nigeria..
    Okafor, Okechukwu C.
    Univ Nigeria, Dept Morbid & Anat Pathol, Ituku Ozalla Campus, Enugu, Nigeria..
    Uche, Nkechinyere Judith
    Univ Nigeria, Dept Ophthalmol, Ituku Ozalla Campus, Enugu, Nigeria..
    Ajuzieogu, Obinna, V
    Univ Nigeria, Dept Anaesthesia, Ituku Ozalla Campus, Enugu, Nigeria..
    Amuta, Dubem S.
    Univ Nigeria, Div Neurosurg, Ituku Ozalla Campus, Enugu, Nigeria..
    Onyia, Ephraim E.
    Univ Nigeria, Div Neurosurg, Ituku Ozalla Campus, Enugu, Nigeria..
    Guga, Dung A.
    Univ Nigeria, Div Neurosurg, Ituku Ozalla Campus, Enugu, Nigeria..
    Okpara, Samuel
    Univ Nigeria, Div Neurosurg, Ituku Ozalla Campus, Enugu, Nigeria..
    Mezue, Wilfred C.
    Univ Nigeria, Div Neurosurg, Ituku Ozalla Campus, Enugu, Nigeria..
    Tisell, Magnus
    Univ Gothenburg, Inst Neurosci & Physiol, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden..
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Pediatric brain tumor care in a Sub-Saharan setting: current poise of a precariously loaded dice2021In: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 35, no 2, p. 174-180Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate the current status of pediatric brain tumor (PBT) care and identify determinants and profiles of survival and school attendance

    Methods: An 8-year institution-based prospective longitudinal study. All cases investigated with neuroimaging and treated were enrolled. Data was analyzed with SPSS (Inc) Chicago IL, USA version 23. Chi Square test, One-way ANOVA and confidence limits were used to evaluate associations at the 95% level of significance. Ethical approval for our study was obtained Health Research Ethics Committee of our hospital.

    Results: Among 103 patients enrolled, 92 satisfied our study criteria. There were 45 males and 39 females, M: F = 0.8. The mean age was 9.5 +/- 2.1 years 95%CI with a range of 7 months to 16 years. The most common symptom was headache for supratentorial lesions (73%) and gait disturbance (80.2%) for infratentorial lesions. More tumors were supratentorial in location 51 (55.4%), 35 (38.1%) were infratentorial and 6 (6.5%) were transtentorial. Craniopharyngiomas (n = 23), medulloblastomas (n = 22) and astrocytomas (n = 15) were the most common tumors. Hemoglobin genotype (AA and AS) had some influence on tumor phenotype FT,P = 0.033. 76 cases were microsurgically resected while 16 patients were treated with radiotherapy alone. The 30-day mortality for operated cases is 7.2 +/- 0.7%. Overall 1-year and 5-year survival was 66.7 and 52.3%, respectively. School attendance, performance and outcome varied among treatment subgroups.

    Conclusion: Survival profile in this series suggests some improvement in comparison to previous studies from our region, Hemoglobin genotype profiles may signature paediatric brain tumor phenotypes in our setting.

  • 38.
    Uche, Enoch Ogbonnaya
    et al.
    Univ Nigeria Ituku Ozalla, Dept Surg, Div Neurosurg, Coll Med, Ituku Ozalla, Enugu, Nigeria..
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Tisell, Magnus
    Sahlgrens Univ Hosp, Dept Neurosurg, Gothenburg, Sweden..
    Scaling Up Global Collaborations for Neurosurgical Education and Care Capacity Development in West Africa: Are There Low-Hanging Fruits Where It Tolls?2020In: World Neurosurgery, ISSN 1878-8750, E-ISSN 1878-8769, Vol. 139, p. 512-518Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Six decades after birth, the path to sustainable neurosurgical education and care in West Africa remains slow paced. We highlight plain sailing local attributes and global interventions for accelerated progress. METHODS: This was a 20-year study of neurosurgical practice and training status from 1999 to 2018. We prospectively evaluated development of neurosurgical units between 2009 and 2018 and compared with retrospective data both from 1999 to 2018 and from the origin of West African neurosurgery in 1962. RESULTS: The number of neurosurgeons rose from 1 in 1962 to 221 in 2018 with a mean of 3.95 neurosurgeons per year. Between 1998 and 2018, the subregional annual neurosurgeon birthrate varied significantly between 0.72 and 3.95. In 1998, 7 countries contributed to a neurosurgeon population of 26. In 2018, 13 countries contributed to a total of 221 neurosurgeons. The period 2009-2018 recorded the highest growth of neurosurgeons with a neurosurgeon birthrate of 7.5. Nigeria accounts for 51.6% (200.9 million) of the West African population and has 57% (11) of the 19 fully accredited training centers, while Ghana and Senegal account for 7.7% and 4.3% of the West African population, respectively, and each has 11% of the training centers. The 10-year unit procreativity index for the period 2009-2018 was 1.3, with Nigeria accounting for 0.7 (53.8%). CONCLUSIONS: The low unit procreativity index across West Africa, a major cause of the low neurosurgeon birthrate, can be resolved using tailored kindling and procreative strategies.

  • 39.
    Uche, Enoch Ogbonnaya
    et al.
    Univ Nigeria, Dept Surg, Neurosurg Unit, Coll Med, Ituku Ozalla, Enugu, Nigeria.;Univ Nigeria, Teaching Hosp, Ituku Ozalla, Enugu, Nigeria..
    Sundblom, Jimmy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Iloabachie, Izuchukwu
    Univ Nigeria, Dept Surg, Neurosurg Unit, Coll Med, Ituku Ozalla, Enugu, Nigeria.;Univ Nigeria, Teaching Hosp, Ituku Ozalla, Enugu, Nigeria..
    Ozoh, Ignatius I.
    ESUTH Med Sch, Dept Surg, Neurosurg Unit, Enugu, Nigeria..
    Alalade, Andrew
    Lancashire Teaching Hosp NHS Fdn Trust, Dept Neurosurg, Preston, Lancs, England..
    Revesz, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Sandvik, Ulrika
    Karolinska Inst, Dept Neurosurg, Stockholm, Sweden..
    Olsson, Martin
    Karolinska Inst, Dept Neurosurg, Stockholm, Sweden..
    Mezue, Wilfred C.
    Univ Nigeria, Dept Surg, Neurosurg Unit, Coll Med, Ituku Ozalla, Enugu, Nigeria.;Univ Nigeria, Teaching Hosp, Ituku Ozalla, Enugu, Nigeria..
    Tisell, Magnus
    Sahlgrens Univ Hosp, Dept Neurosurg, Gothenburg, Sweden..
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Pilot application of Lecture-Panel-Discussion Model (LPDM) in global collaborative neurosurgical education: a novel training paradigm innovated by the Swedish African Neurosurgery Collaboration2022In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 164, no 4, p. 967-972Article in journal (Refereed)
    Abstract [en]

    Background Disruptions in global surgery educational routines by the COVID-19 pandemic have elicited demands for alternative formats for rendering qualitative neurosurgical education. This study presents application of a novel model of online neurosurgical course, the Lecture-Panel-Discussion Model (LPDM). Methods This is a cross-sectional survey of participants who attended the Swedish African Neurosurgery Collaboration (SANC)-100A course. Participants evaluated the course through an online self-administered questionnaire using a 5-point Likert scale ranging from very poor-1, poor-2, average (fair)-3, good-4, to excellent-5. SANC-100A comprises a tripod of Lectures, Panel review, and interactive case Discussion. This model (LPDM) was innovated by SANC and applied at the Enugu International Neurosurgery course in February 2021. Results There were 71 attendees, 19 were course faculty, while 52 were participants. Thirty-five attended from Nigeria, 11 from Sweden, 3 from Malawi, 2 from Senegal, and 1 from the UK. Among 44 participants who completed the questionnaire, there were 9 fellows and 35 residents. The overall median course Likert rating was 4.65 +/- 0.1. The median overall rating for course events was similar between day 1 (Likert score = 4.45) and day 2 (Likert score = 4.55), U = 55, Z score = 1.10, P = 0.27. The median rating for lectures was 4.50 +/- 0.2 and varied from 4.40 on day 1 to 4.55 on day 2. The median rating for panel review was 4.60 +/- 0.1 and varied from 4.55 on day 1 to 4.65 on day 2. Interactive case discussions were rated 4.80 on both course days. There was a significant variability in the rating profiles of the course tripod: U = 24.5, P = 0.03. Fifty-one (98%) participants believe LPDM was COVID-19-compliant, while 90% believe the course was beneficial to training and practice. Conclusion Initial application of LPDM is rewarded with both high acceptance and high rating among participants.

  • 40.
    Virhammar, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Jackmann, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Sköld, Mattias K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Kadir, Mohamed
    Frick, Jens
    Lindeberg, Jonas
    Olivero-Reinius, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Cunningham, Janet L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Grabowska, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bondeson, Kåre
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Zetterberg, Henrik
    Rostami, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid2020In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 95, no 10, p. 445-449Article in journal (Refereed)
    Abstract [en]

    Here, we report a case of COVID-19–related acute necrotizing encephalopathy where SARS-CoV-2 RNA was found in CSF 19 days after symptom onset after testing negative twice. Although monocytes and protein levels in CSF were only marginally increased, and our patient never experienced a hyperinflammatory state, her neurologic function deteriorated into coma. MRI of the brain showed pathologic signal symmetrically in central thalami, subinsular regions, medial temporal lobes, and brain stem. Extremely high concentrations of the neuronal injury markers neurofilament light and tau, as well as an astrocytic activation marker, glial fibrillary acidic protein, were measured in CSF. Neuronal rescue proteins and other pathways were elevated in the in-depth proteomics analysis. The patient received IV immunoglobulins and plasma exchange. Her neurologic status improved, and she was extubated 4 weeks after symptom onset. This case report highlights the neurotropism of SARS-CoV-2 in selected patients and emphasizes the importance of repeated lumbar punctures and CSF analyses in patients with suspected COVID-19 and neurologic symptoms.

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