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  • 1.
    Berntsson, Shala Ghaderi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Falk, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Savitcheva, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Godau, Andrea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Zetterling, Maria
    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.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Perfusion and diffusion MRI combined with (11)C-methionine PET in the preoperative evaluation of suspected adult low-grade gliomas2013In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 114, no 2, p. 241-249Article in journal (Refereed)
    Abstract [en]

    Perfusion and diffusion magnetic resonance imaging (pMRI, dMRI) are valuable diagnostic tools for assessing brain tumors in the clinical setting. The aim of this study was to determine the correlation of pMRI and dMRI with (11)C-methionine positron emission tomography (MET PET) in suspected low-grade gliomas (LGG) prior to surgery. Twenty-four adults with suspected LGG were enrolled in an observational study and examined by MET PET, pMRI and dMRI. Histological tumor diagnosis was confirmed in 23/24 patients (18 gliomas grade II, 5 gliomas grade III). The maximum relative cerebral blood volume (rCBVmax) and the minimum mean diffusivity (MDmin) were measured in tumor areas with highest MET uptake (hotspot) on PET by using automated co-registration of MRI and PET scans. A clearly defined hotspot on PET was present in all 23 tumors. Regions with rCBVmax corresponded with hotspot regions in all tumors, regions with MDmin corresponded with hotspot regions in 20/23 tumors. The correlation between rCBVmax (r = 0.19, P = 0.38) and MDmin (r = -0.41, P = 0.053) with MET uptake in the hotspot was not statistically significant. Taken into account the difficulties of measuring perfusion abnormalities in non-enhancing gliomas, this study demonstrates that co-registered MET PET and pMRI facilitates the identification of regions with rCBVmax. Furthermore, the lack of a clear positive correlation between tumor metabolism in terms of MET uptake and tumor vascularity measured as rCBVmax suggests that combined pMRI/PET provides complementary baseline imaging data in these tumors.

  • 2.
    Duffau, Hugues
    et al.
    Montpellier Med Univ Ctr, Hop Guide Chauliac, Dept Neurosurg, Montpellier, France.;Inst Neurosci, INSERM U1051, Montpellier, France.;Univ Montpellier, Montpellier, France..
    Mandonnet, Emmanuel
    Lariboisiere Hosp, AP HP, Dept Neurosurg, Paris, France.;Univ Paris 07, Paris, France.;IMNC, UMR 8165, Orsay, France..
    Pallud, Johan
    St Anna Hosp, Dept Neurosurg, Paris, France.;Paris Descartes Univ, Sorbonne Paris Cite, Paris, France.;INSERM, U894, Ctr Psychiat & Neurosci, Paris, France..
    Krieg, Sandro
    Tech Univ Munich, Klinikum Rechts Isar, Dept Neurosurg, Munich, Germany..
    Gil Robles, Santiago
    Hosp Univ Quiron, Madrid, Spain.;Bio Cruces Res, Bilbao, Spain..
    Hamer, Philip de Witt
    Vrije Univ Amsterdam Med Ctr, Neurosurg Ctr Amsterdam, Amsterdam, Netherlands..
    Schucht, Philippe
    Univ Hosp Bern, Dept Neurosurg, Bern, Switzerland..
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Santarius, Thomas
    Univ Cambridge, Addenbrookes Hosp, Dept Neurosurg, Cambridge, England..
    Colle, Henry
    AZ St Luca, Funct Neurosurg, Ghent, Belgium..
    Ryan, Mathew
    Leeds Gen Infirm, Dept Neurosurg, Leeds, W Yorkshire, England..
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Inst Neurosci & Physiol, Gothenburg, Sweden..
    von Campe, Gord
    Med Univ Graz, Dept Neurosurg, Graz, Austria..
    Bello, Lorenzo
    Univ Milan, Dept Oncol & Hematooncol, Neurosurg Oncol Unit, Milan, Italy.;IRCCS, Humanitas Res Hosp, Milan, Italy..
    Forster, Marie-Therese
    Goethe Univ, Dept Neurosurg, Frankfurt, Germany..
    Sarubbo, Silvio
    Santa Chiara Hosp, Struct & Funct Connectiv Lab, Trento, Italy..
    Spena, Giannantonio
    Spedali Civil Brescia, Clin Neurochirurg, Brescia, Italy..
    Baron, Marie-Helene
    CHRU Jean Minjoz, Dept Oncol Radiotherapie, Besancon, France..
    Yordanova, Yordanka
    Percy Army Training Hosp, Neurosurg Dept, Clamart, France..
    Darlix, Amelie
    Inst Regional Canc Montpellier ICM, Dept Med Oncol, Montpellier, France..
    Viegas, Catarina
    Hosp Garcia Orta, Dept Neurosurg, Almada, Portugal..
    Almairac, Fabien
    Univ Hosp Nice, Dept Neurosurg, Nice, France..
    Martino, Juan
    Hosp Univ Marques Valdecilla, Fdn Inst Invest Marques Valdecilla IDIVAL, Dept Neurol Surg, Avda Valdecilla S-N, Santander, Spain.;Inst Salud Carlos III, Avda Valdecilla S-N, Santander, Spain..
    Goodden, John
    Dept Neurosurg, Leeds, W Yorkshire, England..
    Chumas, Paul
    Dept Neurosurg, Leeds, W Yorkshire, England..
    Freyschlag, Christian
    Med Univ Innsbruck, Dept Neurosurg, Innsbruck, Austria..
    Robe, Pierre
    Univ Med Ctr Utrecht, Dept Neurosurg, Utrecht, Netherlands..
    Wager, Michel
    Univ Poitiers Hosp, INSERM U1084, Neurosurg Dept, Poitiers, France..
    Polivka, Marc
    Lariboisiere Hosp, AP HP, Dept Neuropathol, Paris, France..
    Giakoumettis, Dimitris
    Neurosurg Evangelismos Hosp, Athens, Greece..
    Robert, Erik
    AZ SintLucas & AZ Maria Middelares, Dept of Aphasiol, Ghent, Belgium..
    Guillevin, Remy
    Univ Poitiers Hosp, Neuroradiol Dept, Poitiers, France..
    Grivas, Athanasios
    Univ Glasgow, Queen Elizabeth Univ Hosp, Inst Neurol Sci, Dept Neurosurg, Glasgow, Lanark, Scotland..
    Fontaine, Denys
    Univ Hosp Nice, Dept Neurosurg, Nice, France..
    van Geemen, Kim
    Brain Res Ctr Amsterdam, Amsterdam, Netherlands..
    Lubrano, Vincent
    Univ Toulouse, CHU Toulouse, Toulouse NeuroImaging Ctr, INSERM UMR 1214,ToNIC, Toulouse, France..
    Rutten, Geert-Jan
    St Elisabeth Tweesteden Hosp, Dept Neurosurg, Tilburg, Netherlands..
    Barone, Fabio
    Cannizzaro Gen Hosp, Dept Neurosurg & Gamma Knife, Catania, Italy..
    Rofes, Adria
    Trinity Coll Dublin, Global Brain Hlth Inst, Dublin, Ireland..
    Rech, Fabien
    CHRU Nancy, Serv Neurochirurg, Nancy, France..
    Rigau, Valerie
    Gui Chauliac Hosp, Dept Pathol, Montpellier, France..
    Wagemakers, Michiel
    Univ Med Ctr, Neurosurg Dept, Groningen, Belgium..
    Papagno, Costanza
    Univ Trento, CeRiN & CIMeC, Rovereto, Italy..
    Aerts, Annelies
    AZ Sint Lucas, Ghent, Belgium.;Artevelde Univ Coll, Ghent, Belgium..
    Visch-Brink, Evy
    Erasmus MC, Dept Neurol, Rotterdam, Netherlands.;Erasmus MC, Dept Neurosurg, Rotterdam, Netherlands..
    Tate, Matthew
    Northwester Med Group, Dept Neurosurg, Chicago, IL USA..
    Garg, Neha
    Univ Delhi, Delhi, India..
    Klein, Martin
    Vrije Univ Amsterdam Med Ctr, Clin Neuropsychol Dept, Amsterdam, Netherlands..
    Satoer, Djaina
    Erasmus MC, Dept Neurol, Rotterdam, Netherlands.;Erasmus MC, Dept Neurosurg, Rotterdam, Netherlands..
    de Witte, Elke
    Vrije Univ Brussel, Neurolinguist Dept, Brussels, Belgium..
    Van Brussel, Lore
    Onze Lieve Vrouw Hosp, Neurosurg Dept, Moorselbaan, Aalst, Belgium..
    Reyes, Andres
    Univ Groningen, Dept Clin Linguist, Groningen, Netherlands.;EMCL Univ Potsdam, Potsdam, Germany.;El Bosque Univ, Expt Psychol Lab, Fac Psychol, Bogota, Colombia.;Inst Neurosci, Bogota, Colombia..
    van Ierschot, Fleur
    Univ Trent, Ctr Mind Brain Sci, Trento, Italy.;Univ Groningen, Fac Arts, Groningen, Belgium.;Macquarie Univ, Dept Cognit Sci, Sydney, NSW, Australia..
    Veenstra, Wencke
    Univ Groningen, Dept Linguist, Groninge, Belgium..
    Snijders, Tom
    Univ Med Ctr Utrecht, Dept Neurol & Neurosurg Hosp, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Taillandier, Luc
    CHU Nancy, Neurol Dept, Nancy, France..
    Blonski, Marie
    CHU Nancy, Neurol Dept, Nancy, France..
    Evidenced-based medicine in glioma: molecular biology is only part of the story2017In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 18, no 8, p. E429-E429Article in journal (Refereed)
  • 3.
    Falk, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Rostrup, Egill
    Berntsson, Shala
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Morell, Arvid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Larsson, Henrik B W
    Smits, Anja
    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 Radiology, Oncology and Radiation Science, Radiology.
    Discrimination between glioma grades II and III in suspected low-grade gliomas using dynamic contrast-enhanced and dynamic susceptibility contrast perfusion MR imaging: a histogram analysis approach2014In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 56, no 12, p. 1031-1038Article in journal (Refereed)
    Abstract [en]

    Introduction

    Perfusion magnetic resonance imaging (MRI) can be used in the pre-operative assessment of brain tumours. The aim of this prospective study was to identify the perfusion parameters from dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) perfusion imaging that could best discriminate between grade II and III gliomas.

    Methods

    MRI (3 T) including morphological ((T2 fluid attenuated inversion recovery (FLAIR) and T1-weighted (T1W)+Gd)) and perfusion (DCE and DSC) sequences was performed in 39 patients with newly diagnosed suspected low-grade glioma after written informed consent in this review board-approved study. Regions of interests (ROIs) in tumour area were delineated on FLAIR images co-registered to DCE and DSC, respectively, in 25 patients with histopathological grade II (n = 18) and III (n  = 7) gliomas. Statistical analysis of differences between grade II and grade III gliomas in histogram perfusion parameters was performed, and the areas under the curves (AUC) from the ROC analyses were evaluated.

    Results

    In DCE, the skewness of transfer constant (k trans) was found superior for differentiating grade II from grade III in all gliomas (AUC 0.76). In DSC, the standard deviation of relative cerebral blood flow (rCBF) was found superior for differentiating grade II from grade III gliomas (AUC 0.80).

    Conclusions

    Histogram parameters from k trans (DCE) and rCBF (DSC) could most efficiently discriminate between grade II and grade III gliomas.

  • 4.
    Falk Delgado, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Markus, Nilsson
    Bioimaging center, Lunds Universitet.
    Ghaderi Berntsson, Shala
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    van Westen, Danielle
    Clinical Sciences, Lunds Universitet.
    Lätt, Jimmy
    MR Department, Center for medical imaging and physiology, Lund University Hospital.
    Smits, Anja
    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.
    Preoperative diffusion kurtosis imaging in suspected low-grade gliomas: A prospective study of diffusional properties in tumour and perilesional regions with histopathological correlationsManuscript (preprint) (Other academic)
  • 5.
    Falk Delgado, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Nilsson, Markus
    Lund Univ, Bioimaging Ctr, Lund, Sweden..
    Berntsson, Shala G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Libard, Sylwia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    van Westen, Danielle
    Lund Univ, Clin Sci Lund, Diagnost Radiol, Lund, Sweden..
    Lätt, Jimmy
    Skane Univ Healthcare, Dept Imaging & Funct, Lund, Sweden..
    Smits, Anja
    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.
    Diffusion kurtosis imaging of gliomas grades II and III: a study of perilesional tumor infiltration, tumor grades and subtypes at clinical presentation2017In: Radiology and Oncology, ISSN 1318-2099, E-ISSN 1581-3207, Vol. 51, no 2, p. 121-129Article in journal (Refereed)
    Abstract [en]

    Background. Diffusion kurtosis imaging (DKI) allows for assessment of diffusion influenced by microcellular structures. We analyzed DKI in suspected low-grade gliomas prior to histopathological diagnosis. The aim was to investigate if diffusion parameters in the perilesional normal-appearing white matter (NAWM) differed from contralesional white matter, and to investigate differences between glioma malignancy grades II and III and glioma subtypes (astrocytomas and oligodendrogliomas).

    Patients and methods. Forty-eight patients with suspected low-grade glioma were prospectively recruited to this institutional review board-approved study and investigated with preoperative DKI at 3T after written informed consent. Patients with histologically proven glioma grades II or III were further analyzed (n=35). Regions of interest (ROIs) were delineated on T2FLAIR images and co-registered to diffusion MRI parameter maps. Mean DKI data were compared between perilesional and contralesional NAWM (student's t-test for dependent samples, Wilcoxon matched pairs test). Histogram DKI data were compared between glioma types and glioma grades (multiple comparisons of mean ranks for all groups). The discriminating potential for DKI in assessing glioma type and grade was assessed with receiver operating characteristics (ROC) curves.

    Results. There were significant differences in all mean DKI variables between perilesional and contralesional NAWM (p=< 0.000), except for axial kurtosis (p=0.099). Forty-four histogram variables differed significantly between glioma grades II (n=23) and III (n=12) (p=0.003-0.048) and 10 variables differed significantly between ACs (n=18) and ODs (n=17) (p=0.011-0.050). ROC curves of the best discriminating variables had an area under the curve (AUC) of 0.657-0.815.

    Conclusions. Mean DKI variables in perilesional NAWM differ significantly from contralesional NAWM, suggesting altered microstructure by tumor infiltration not depicted on morphological MRI. Histogram analysis of DKI data identifies differences between glioma grades and subtypes.

  • 6.
    Falk Delgado, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Nilsson, Markus
    Latini, Francesco
    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.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Berntsson, Shala G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Lätt, Jimmy
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Preoperative Quantitative MR Tractography Compared with Visual Tract Evaluation in Patients with Neuropathologically Confirmed Gliomas Grades II and III: A Prospective Cohort Study2016In: Radiology Research and Practice, ISSN 2090-1941, E-ISSN 2090-195X, article id 7671854Article in journal (Refereed)
    Abstract [en]

    Background and Purpose. Low-grade gliomas show infiltrative growth in white matter tracts. Diffusion tensor tractography can noninvasively assess white matter tracts. The aim was to preoperatively assess tumor growth in white matter tracts using quantitative MR tractography (3T). The hypothesis was that suspected infiltrated tracts would have altered diffusional properties in infiltrated tract segments compared to noninfiltrated tracts. Materials and Methods. Forty-eight patients with suspected low-grade glioma were included after written informed consent and underwent preoperative diffusion tensor imaging in this prospective review-board approved study. Major white matter tracts in both hemispheres were tracked, segmented, and visually assessed for tumor involvement in thirty-four patients with gliomas grade II or III (astrocytomas or oligodendrogliomas) on postoperative neuropathological evaluation. Relative fractional anisotropy (rFA) and mean diffusivity (rMD) in tract segments were calculated and compared with visual evaluation and neuropathological diagnosis. Results. Tract segment infiltration on visual evaluation was associated with a lower rFA and high rMD in a majority of evaluated tract segments (89% and 78%, resp.). Grade II and grade III gliomas had similar infiltrating behavior. Conclusion. Quantitative MR tractography corresponds to visual evaluation of suspected tract infiltration. It may be useful for an objective preoperative evaluation of tract segment involvement.

  • 7. Freyschlag, Christian F
    et al.
    Krieg, Sandro M
    Kerschbaumer, Johannes
    Pinggera, Daniel
    Forster, Marie-Therese
    Cordier, Dominik
    Rossi, Marco
    Miceli, Gabriele
    Roux, Alexandre
    Reyes, Andrés
    Sarubbo, Silvio
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Sierpowska, Joanna
    Robe, Pierre A
    Rutten, Geert-Jan
    Santarius, Thomas
    Matys, Tomasz
    Zanello, Marc
    Almairac, Fabien
    Mondot, Lydiane
    Jakola, Asgeir S
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Rofes, Adrià
    von Campe, Gord
    Guillevin, Remy
    Bagatto, Daniele
    Lubrano, Vincent
    Rapp, Marion
    Goodden, John
    De Witt Hamer, Philip C
    Pallud, Johan
    Bello, Lorenzo
    Thomé, Claudius
    Duffau, Hugues
    Mandonnet, Emmanuel
    Imaging practice in low-grade gliomas among European specialized centers and proposal for a minimum core of imaging.2018In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 139, no 3, p. 699-711Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers.

    METHODS: An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery.

    RESULTS: A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI.

    CONCLUSION: A minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of ≤ 3 mm. No common standard could be obtained regarding advanced MRI protocols and PET.

    IMPORTANCE OF THE STUDY: We believe that our study makes a significant contribution to the literature because we were able to determine similarities in numerous aspects of LGG imaging. Using the proposed "minimal core of imaging" in clinical routine will facilitate future cooperative studies.

  • 8.
    Hedlund, Mathilde
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Zetterling, Maria
    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.
    Carlsson, Marianne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Depression and posttraumatic stress disorder after aneurysmal subarachnoid hemorrhage in relation to lifetime psychiatric morbidity2011In: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 25, no 6, p. 693-700Article in journal (Refereed)
    Abstract [en]

    Introduction. Little is known about the roles that lifetime psychiatric disorders play in psychiatric and vocational outcomes of aneurysmal subarachnoid haemorrhage (SAH). Materials and methods. Eighty-three SAH patients without apparent cognitive dysfunction were assessed using the Structured Clinical Interview for DSM-IV axis I disorders (SCID-I) after their SAH. Diagnoses were assessed for three time periods, 'lifetime before SAH', '12 months before SAH' and '7 months after SAH'. Results. Forty-five percentage of patients with SAH reported at least one lifetime psychiatric disorder. After SAH, symptoms of depression and/or post-traumatic stress disorder (PTSD) were seen in 41%, more often in those with a psychiatric history prior to SAH (p = 0.001). In logistic regressions, depression after SAH was associated with a lifetime history of major depression, or of anxiety or substance use disorder, as well as with lifetime psychiatric comorbidity. Subsyndromal or full PTSD was predicted by a lifetime history of major depression. After the SAH, 18 patients (22%) had received psychotropic medication and/or psychological treatment, 13 of whom had a disorder. Those with a lifetime history of major depression or treatment with antidepressants before SAH had lower return to work rates than others (p = 0.019 and p = 0.031, respectively). This was also true for those with symptoms of depression and/or PTSD, or with antidepressant treatment after SAH (p = 0.001 and p = 0.031, respectively). Conclusions. Depression and PTSD are present in a substantial proportion of patients 7 months after SAH. Those with a history of psychiatric morbidity, any time before the SAH, are more at risk and also constitute a risk group for difficulties in returning to work.

  • 9.
    Libard, Sylwia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Popova, Svetlana N
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Department of Pathology, Uppsala University Hospital, Uppsala, Sweden.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Kärjä, Vesa
    Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
    Pietiläinen, Timo
    Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
    Hämäläinen, Kirsi M
    Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Hesselager, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. Department of Neurosurgery, Uppsala University Hospital, Sweden.
    Bergqvist, Michael
    Department of radiation sciences, Umeå University, Sweden.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Pfeifer, Susan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    de Ståhl, Teresita Diaz
    Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Karolinska University Hospital, Stockholm, Sweden.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Human cytomegalovirus tegument protein pp65 is detected in all intra- and extra-axial brain tumours independent of the tumour type or grade2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 9, p. e108861-Article in journal (Refereed)
    Abstract [en]

    Human cytomegalovirus (HCMV) has been indicated being a significant oncomodulator. Recent reports have suggested that an antiviral treatment alters the outcome of a glioblastoma. We analysed the performance of commercial HCMV-antibodies applying the immunohistochemical (IHC) methods on brain sample obtained from a subject with a verified HCMV infection, on samples obtained from 14 control subjects, and on a tissue microarray block containing cores of various brain tumours. Based on these trials, we selected the best performing antibody and analysed a cohort of 417 extra- and intra-axial brain tumours such as gliomas, medulloblastomas, primary diffuse large B-cell lymphomas, and meningiomas. HCMV protein pp65 immunoreactivity was observed in all types of tumours analysed, and the IHC expression did not depend on the patient's age, gender, tumour type, or grade. The labelling pattern observed in the tumours differed from the labelling pattern observed in the tissue with an active HCMV infection. The HCMV protein was expressed in up to 90% of all the tumours investigated. Our results are in accordance with previous reports regarding the HCMV protein expression in glioblastomas and medulloblastomas. In addition, the HCMV protein expression was seen in primary brain lymphomas, low-grade gliomas, and in meningiomas. Our results indicate that the HCMV protein pp65 expression is common in intra- and extra-axial brain tumours. Thus, the assessment of the HCMV expression in tumours of various origins and pathologically altered tissue in conditions such as inflammation, infection, and even degeneration should certainly be facilitated.

  • 10.
    Mandonnet, Emmanuel
    et al.
    Lariboisiere Hosp, AP HP, Dept Neurosurg, Paris, France.;Univ Paris 07, Paris, France.;IMNC UMR8165, Orsay, France..
    Wager, Michel
    Univ Poitiers Hosp, INSERM U1084, Dept Neurosurg, Poitiers, France..
    Almairac, Fabien
    Univ Hosp Nice, Hop Pasteur 2, Dept Neurosurg, Nice, France..
    Baron, Marie-Helene
    CHU Besancon, Dept Radiotherapy, Besancon, France..
    Blonski, Marie
    Nancy Neurol Hosp, Dept Neurooncol, Nancy, France..
    Freyschlag, Christian F.
    Med Univ Innsbruck, Dept Neurosurg, Innsbruck, Austria..
    Barone, Fabio
    Cannizzaro Gen Hosp, Dept Neurosurg, Catania, Italy.;Cannizzaro Gen Hosp, Gamma Knife, Catania, Italy..
    Fontaine, Denys
    Univ Hosp Nice, Hop Pasteur 2, Dept Neurosurg, Nice, France..
    Pallud, Johan
    St Anne Hosp, Dept Neurosurg, Paris, France..
    Hegi, Monika
    Lausanne Univ Hosp, Neurosci Res Ctr, Lausanne, Switzerland..
    Viegas, Catarina
    Hosp Garcia de Orta, Dept Neurosurg, Almada, Portugal..
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Spena, Giannantonio
    Spedali Civil Brescia, Dept Neurosurg, Brescia, Italy.;Univ Brescia, Brescia, Italy..
    Goodden, John
    Leeds Gen Infirm, Leeds, W Yorkshire, England..
    Rutten, Geert-Jan
    St Elizabeth Hosp, Dept Neurosurg, Curacao, Neth Antilles..
    Taillandier, Luc
    Nancy Neurol Hosp, Dept Neurooncol, Nancy, France..
    Foroglu, Nicolas
    Aristotelian Univ Thessaloniki, Neurosurg Dept, AHEPA Hosp, Thessaloniki, Greece..
    Darlix, Amelie
    Inst Reg Canc Montpellier ICM, Dept Med Oncol, Montpellier, France..
    Skrap, Miran
    Azienda Osped Univ SMM, Dept Neurosurg, Udine, Italy..
    Martino, Juan
    Hosp Univ Marques de Valdecilla, Dept Neurol Surg, Santander, Spain.;Fdn Inst Invest Marques de Valdecilla IDIVAL, Santander, Spain..
    von Campe, Gord
    Med Univ Graz, Dept Neurosurg, Graz, Austria..
    Madadaki, Caterina
    Lariboisiere Hosp, AP HP, Dept Anesthesiol, Paris, France..
    Gayat, Etienne
    Lariboisiere Hosp, AP HP, Dept Anesthesiol, Paris, France..
    Hamer, Philip de Witt
    Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Gil Robles, Santiago
    Hosp Quiron, Dept Neurosurg, Madrid, Spain.;Inst Invest BIOCRUCES, Bilbao, Spain..
    Sarubbo, Silvio
    Santa Chiara Hosp, Div Neurosurg, Dept Neurosci, Struct & Funct Connect Lab Project, Trento, Italy..
    Santorius, Thomas
    Univ Cambridge, Addenbrookes Hosp, Dept Neurosurg, Cambridge, England..
    Bello, Lorenzo
    Ist Clin Humanitas, Dept Neurosurg, Milan, Italy..
    Forster, Marie-Therese
    Goethe Univ, Dept Neurosurg, Frankfurt, Germany..
    Duffau, Hugues
    Montpellier Med Univ Ctr, Hop Gui Chauliac, Dept Neurosurg, Montpellier, France..
    Survey on current practice within the European Low-Grade Glioma Network: where do we stand and what is the next step?2017In: NEURO-ONCOLOGY PRACTICE, ISSN 2054-2577, Vol. 4, no 4, p. 241-247Article in journal (Refereed)
    Abstract [en]

    Diffuse low-grade glioma form a rare entity affecting young people. Despite advances in surgery, chemotherapy, and radiation therapy, diffuse low-grade glioma are still incurable. According to current guidelines, maximum safe resection, when feasible, is the first line of treatment. Apart from surgery, all other treatment modalities (temozolomide, procarbazine-CCNU-vincristine regimen, and radiation therapy) are handled very differently among different teams, and this in spite of recent results of several phase 3 studies. Based on a European survey, this paper aimed to get a picture of this heterogeneity in diffuse low-grade glioma management, to identify clinically relevant questions raised by this heterogeneity of practice, and to propose new methodological frameworks to address these questions.

  • 11. Rofes, Adrià
    et al.
    Mandonnet, Emmanuel
    Godden, John
    Baron, Marie Hélène
    Colle, Henry
    Darlix, Amelie
    de Aguiar, Vânia
    Duffau, Hugues
    Herbet, Guillaume
    Klein, Martin
    Lubrano, Vincent
    Martino, Juan
    Mathew, Ryan
    Miceli, Gabriele
    Moritz-Gasser, Sylvie
    Pallud, Johan
    Papagno, Costanza
    Rech, Fabien
    Robert, Erik
    Rutten, Geert-Jan
    Santarius, Thomas
    Satoer, Djaina
    Sierpowska, Joanna
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Skrap, Miran
    Spena, Giannantonio
    Visch, Evy
    De Witte, Elke
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Wager, Michel
    Survey on current cognitive practices within the European Low-Grade Glioma Network: towards a European assessment protocol.2017In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 159, no 7, p. 1167-1178Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The European Low-Grade Glioma network indicated a need to better understand common practices regarding the managing of diffuse low-grade gliomas. This area has experienced great advances in recent years.

    METHOD: A general survey on the managing of diffuse low-grade gliomas was answered by 21 centres in 11 European countries. Here we focused on specific questions regarding perioperative and intraoperative cognitive assessments.

    RESULTS: More centres referred to the same speech and language therapist and/or neuropsychologist across all assessments; a core of assessment tools was routinely used across centres; fluency tasks were commonly used in the perioperative stages, and object naming during surgery; tasks that tapped on attention, executive functions, visuospatial awareness, calculation and emotions were sparsely administered; preoperative assessments were performed 1 month or 1 week before surgery; timing for postoperative assessments varied; finally, more centres recommended early rehabilitation, whenever needed.

    CONCLUSIONS: There is an emerging trend towards following similar practices for the management of low-grade gliomas in Europe. Our results are descriptive and formalise current discussions in our group. Also, they contribute towards the development of a European assessment protocol.

  • 12.
    Roodakker, Kenney Roy
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Alhuseinalkhudhur, Ali
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Al-Jaff, Mohammed
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Georganaki, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Berntsson, Shala G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Edqvist, Per-Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Dimberg, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    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.
    Region-by-region analysis of PET, MRI, and histology in en bloc-resected oligodendrogliomas reveals intra-tumoral heterogeneity2019In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 46, no 3, p. 569-579Article in journal (Refereed)
  • 13.
    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.

  • 14.
    Smits, Anja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lundin, Margareta
    Melin, Beatrice
    Fahlström, Markus
    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.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Berntsson, Shala Ghaderi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Neurological Impairment Linked with Cortico-Subcortical Infiltration of Diffuse Low-Grade Gliomas at Initial Diagnosis Supports Early Brain Plasticity2015In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 6, article id 137Article in journal (Refereed)
    Abstract [en]

    Diffuse low-grade gliomas (DLGG) are slow-growing brain tumors that in spite of an indolent behavior at onset show a continuous expansion over time and inevitably transform into malignant gliomas. Extensive tumor resections may be performed with preservation of neurological function due to neuroplasticity that is induced by the slow tumor growth. However, DLGG prefer to migrate along subcortical pathways, and white matter plasticity is considerably more limited than gray matter plasticity. Whether signs of functional decompensating white matter that may be found as early as at disease presentation has not been systematically studied. Here, we examined 52 patients who presented with a DLGG at the time of radiological diagnosis. We found a significant correlation between neurological impairment and eloquent cortico-subcortical tumor localization, but not between neurological function and tumor volume. These results suggest that even small tumors invading white matter pathways may lack compensatory mechanisms for functional reorganization already at disease presentation.

  • 15.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Regarding "Somatotropic and thyroid hormones in the acute phase of subarachnoid hemorrhage"2014In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 156, no 5, p. 977-977Article in journal (Other academic)
  • 16.
    Zetterling, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Berhane, Luwam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Jakola, Asgeir S
    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.
    Prognostic markers for survival in patients with oligodendroglial tumors; a single-institution review of 214 cases2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 11, article id e0188419Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In the 2016 WHO classification, the diagnosis of oligodendroglioma has been restricted to IDH mutated, 1p19q codeleted tumors (IDHmut-codel). IDHmut oligoastrocytoma is now classified either as oligodendroglioma or astrocytoma based on presence of 1p19q codeletion. There is growing evidence that this molecular classification more closely reflects patient outcome. Due to the strong association between IDHmut-codel with oligodendroglial morphology, the additional impact of these markers on prognostic accuracy is largely unknown. Our aim was to assess the prognostic impact of IDHmut-codel in an unselected cohort of morphologically classified oligodendroglial tumors.

    METHODS: We performed a retrospective chart review of oligodendroglial tumors (WHO grade II and III) operated since 1983. A total of 214 tumors were included, and molecular information was available for 96 tumors. The prognostic impact of IDHmut-codel together with clinical parameters was analyzed by multivariate Cox regression.

    RESULTS: IDHmut-codel was registered in 64 tumors while for 150 tumors the molecular profile was negative for IDHmut-codel, unknown or incomplete. Comparison between the two groups showed that patients with IDHmut-codel tumors were younger (42 vs. 48 years), had more frequent frontal tumor location (48 vs. 33%) and presented more often with seizures (72 vs. 51%) and no signs of neurological impairment (14 vs. 30%) than patients harboring tumors with unknown or incomplete molecular profile. Multivariate survival analysis identified young age (HR 1.78 ≥ 40 years), the absence of neurological deficits or personality changes (HR 0.57), frontal tumor location (HR 0.64) and the presence of IDHmut-codel (HR 0.50) as independent predictors for longer survival, whereas tumor grade was not.

    CONCLUSION: In this unselected single-institution cohort, the presence of IDHmut-codel was associated with more beneficial clinical parameters and was identified as an independent prognostic factor. We conclude that the classical oligodendroglioma genotype provides additional prognostic data beyond clinical characteristics, morphology and tumor grade.

  • 17.
    Zetterling, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Edén Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hallberg, Lena
    Hillered, Lars
    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.
    Karlsson, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Cortisol and adrenocorticotropic hormone dynamics in the acute phase of subarachnoid haemorrhage2011In: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 25, no 6, p. 684-692Article in journal (Refereed)
    Abstract [en]

    Objective. An adequate response of hypothalamic-pituitary-adrenal (HPA) axis is important for survival and recovery after a severe disease. The hypothalamus and the pituitary glands are at risk of damage after subarachnoid haemorrhage (SAH). A better understanding of the hormonal changes would be valuable for optimising care in the acute phase of SAH. Patients. Fifty-five patients with spontaneous SAH were evaluated regarding morning concentrations of serum (S)-cortisol and P-adrenocorticotropic hormone (ACTH) 7 days after the bleeding. In a subgroup of 20 patients, the diurnal changes of S-cortisol and P-ACTH were studied and urine (U)-cortisol was measured. The relationships of hormone concentrations to clinical and radiological parameters and to outcome were assessed. Results. S-cortisol and P-ACTH were elevated the day of SAH. S-cortisol concentrations below reference range were uncommon. Early global cerebral oedema was associated with higher S-cortisol concentrations at admission and a worse World Federation of Neurological Surgeons (WFNS) and Reaction Level Scale 85 grade. Global cerebral oedema was shown to be a predictor of S-cortisol at admittance. Patients in better WFNS grade displayed higher U-cortisol. All patients showed diurnal variations of S-cortisol and P-ACTH. A reversed diurnal variation of S-cortisol was more frequently found in mechanically ventilated patients. Periods of suppressed P-ACTH associated with S-cortisol peaks occurred especially in periods of secondary brain ischaemia. Conclusion. There was an HPA response acutely after SAH with an increase in P-ACTH and S-cortisol. Higher U-cortisol in patients in a better clinical grade may indicate a more robust response of the HPA system. Global cerebral oedema was associated with higher S-cortisol at admission and was a predictor of S-cortisol concentrations. Global cerebral oedema may be the result of the stress response initiated by the brain injury. Periods of suppressed P-ACTH occurred particularly in periods of brain ischaemia, indicating a possible connection between brain ischaemia and ACTH suppression.

  • 18.
    Zetterling, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Engström, Britt Edén
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Arnardottir, Steinunn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Somatotropic and thyroid hormones in the acute phase of subarachnoid haemorrhage2013In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 155, no 11, p. 2053-2062Article in journal (Refereed)
    Abstract [en]

    Somatotropic and thyroid hormones are probably important for the recovery after acute brain injury. Still, the dynamics of these hormones after spontaneous subarachnoid haemorrhage (SAH) is not well described. The purpose of this study was to investigate the relation between somatotropic and thyroid hormones and clinical factors after SAH. Twenty patients with spontaneous SAH were included prospectively. Serum concentrations of TSH, fT4, T3, IGF-1 and GH were measured once a day for 7 days after SAH. Hormone patterns and serum concentrations were compared to the severity of SAH, neurological condition at admission, clinical course and outcome of the patients. During the first week after SAH, all patients showed increased GH and IGF-1 concentrations. In the whole group, concentrations of TSH increased, whereas T3 and fT4 decreased. There were no relations of serum concentrations of IGF-1 or GH to clinical condition at admission, clinical course or outcome of the patients. Half of the patients showed low T3 serum concentrations. A complicated course was associated with a deeper fall in TSH and T3 concentrations. There were negative correlations for mean concentrations of TSH and T3 versus WFNS grade and a positive correlation for T3 versus GOS after 6 months, indicating that low concentrations of TSH and T3 were connected to worse SAH grade and poor outcome. All patients showed increased GH and IGF-1 concentrations irrespective of the grade of SAH or clinical course. Patients with a complicated clinical course showed a more pronounced fall in TSH and T3 concentrations and low serum T3 concentrations were related to a more serious SAH and poor patient outcome. These results need to be studied further and they may contribute to the accumulated knowledge needed to understand the complex mechanisms influencing the unpredictable clinical course after SAH.

  • 19.
    Zetterling, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hallberg, Lena
    Department of Radiology Karolinska University Hospital, Huddinge.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Karlsson, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    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.
    Brain energy metabolism in patients with spontaneous subarachnoid hemorrhage and global cerebral edema2010In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 66, no 6, p. 1102-1110Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Previous studies of spontaneous subarachnoid hemorrhage (SAH) have shown that global cerebral edema on the first computed tomography scan is associated with a more severe initial injury and is an independent predictor of poor outcome. Effects of secondary ischemic events also influence outcome after SAH. OBJECTIVE: This study demonstrates that early global edema is related to markers of an increased cerebral energy metabolism as measured with intracerebral microdialysis, which could increase vulnerability to adverse events. METHODS: Fifty-two patients with microdialysis monitoring after spontaneous SAH were stratified according to the occurrence of global cerebral edema on the first computed tomography scan taken a median of 2 hours after the initial bleed. Microdialysis levels of glucose, lactate, and pyruvate were compared between the global edema (n = 31) and no global edema (n = 21) groups. Clinical outcome was assessed with the Glasgow Outcome Scale score at >/= 6 months. RESULTS: Patients with global edema showed significantly elevated lactate and pyruvate levels 70 to 79 hours after SAH and marginally significantly higher levels of lactate 60 to 69 hours and 80 to 89 hours after SAH. There was a trend toward worse outcome in the edema group. CONCLUSION: Patients with global cerebral edema have higher interstitial levels of lactate and pyruvate. The edema group may have developed a cerebral hypermetabolism to meet the increased energy demand in the recovery phase after SAH. This stress would make the brain more vulnerable to secondary insults, increasing the likelihood of energy failure.

  • 20.
    Zetterling, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hallberg, Lena
    Department of Radiology Karolinska University Hospital, Huddinge.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Early global brain oedema in relation to clinical admission parameters and outcome in patients with aneurysmal subarachnoid haemorrhage2010In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 152, no 9, p. 1527-1533Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Previous studies on spontaneous aneurysmal subarachnoid haemorrhage (SAH) treatment have found the presence of global cerebral oedema on the first CT scan to be a predictor of poor outcome. We have reviewed our own experience with SAH in order to evaluate the relation of global cerebral oedema to clinical parameters at admission and to functional outcome. METHODS: One hundred ninety patients with spontaneous aneurysmal SAH were included in the study. The first CT scan for each patient was evaluated for signs of global cerebral oedema. Clinical status on admission was assessed according to the Hunt & Hess score and the World Federation of Neurosurgical Societies (WFNS) grade and functional outcome using the Glasgow Outcome Scale (GOS). Clinical condition at admission was dichotomised as 'better' (Hunt & Hess 1-2, WFNS 1-2) or 'worse' (Hunt & Hess 3-5, WFNS 3-5) and outcome as 'favourable' (GOS 4-5) or 'poor' (GOS 1-3). The amount of blood on the CT scan was assessed using the Fisher scale. Comparisons were made between patients with and without global cerebral oedema on the first CT regarding clinical condition, age, gender, mode of aneurysm treatment, outcome, 6-month mortality, amount of blood on the CT scan and time lag to the first CT scan. RESULTS: Global cerebral oedema was observed in 57% of patients admitted with aneurysmal SAH, which is a much higher frequency than has been reported previously. Patients with oedema were admitted in a worse clinical status, but there was no difference between patients with and without oedema regarding other clinical parameters or outcome. The median time between the haemorrhage and the first CT scan was short compared to earlier studies, 2.5 h for those with oedema and 3.4 for those without. This difference was significant, suggesting that global cerebral oedema can be a very early phenomenon after SAH, and may be missed in later CT scans. Early global brain oedema, occurring within a few hours of bleeding, may be more common than previously thought. In aneurysmal SAH patients, the presence of global cerebral oedema was associated with a worse clinical condition at admission which in turn could indicate a more severe initial injury. The clinical significance of early oedema may differ from that of late oedema, which may explain the lack of an association between global oedema and poor outcome in this study. However, the nature of the oedema as well as its relation to the clinical course has to be further studied in separate studies.

  • 21.
    Zetterling, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Roodakker, Kenney Roy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Berntsson, Shala Ghaderi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Edqvist, Per-Henrik D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Latini, Francesco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Linköping Univ, Ctr Med Image Sci & Visualizat, Linköping, Sweden.
    Pontén, Fredrik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    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. Danish Epilepsy Ctr, Dianalund, Denmark.
    Extension of diffuse low-grade gliomas beyond radiological borders as shown by the coregistration of histopathological and magnetic resonance imaging data2016In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 125, no 5, p. 1155-1166Article in journal (Refereed)
    Abstract [en]

    Background: Magnetic resonance imaging tends to underestimate the extent of diffuse low-grade gliomas (DLGGs). With the aim of studying the presence of tumor cells outside the radiological border, the authors developed a method of correlating MRI findings with histological data in patients with suspected DLGGs in whom en bloc resections were performed.

    Methods: Five patients with suspected DLGG suitable for en bloc resection were recruited from an ongoing prospective study. Sections of the entire tumor were immunostained with antibodies against mutated IDH1 protein (IDH1-R132H). Magnetic resonance images were coregistered with corresponding IDH1 images. The growth pattern of tumor cells in white and gray matter was assessed in comparison with signal changes on corresponding MRI slices.

    Results: Neuropathological assessment revealed DLGG in 4 patients and progression to WHO Grade III glioma in 1 patient. The tumor core consisted of a high density of IDH1-R132H–positive tumor cells and was located in both gray and white matter. Tumor cells infiltrated along the peripheral fibers of the white matter tracts. In all cases, tumor cells were found outside the radiological tumor border delineated on T2-FLAIR MRI sequences.

    Conclusions: The authors present a new method for the coregistration of histological and radiological characteristics of en bloc–removed infiltrative brain tumors that discloses tumor invasion at the radiological tumor borders. This technique can be applied to evaluate the sensitivity of alternative imaging methods to detect scattered tumor cells at tumor borders. Accurate methods for detection of infiltrative tumor cells will improve the possibility of performing radical tumor resection. In future studies, the method could also be used for in vivo studies of tumor invasion.

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