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Epileptic seizures and survival in early disease of grade 2 gliomas
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 Neuroscience, Neurology.
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 Neuroscience, Neurology.
2009 (English)In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 16, no 7, 823-831 p.Article in journal (Refereed) Published
Abstract [en]

Background and purpose

The aims of this study were (i) to determine the correlation between seizure activity and the metabolic rate of the tumour measured by 11Cmethionine PET (MET PET) in patients with grade 2 gliomas, and (ii) to assess the prognostic impact of early seizure manifestations on patient survival.

Methods

In this retrospective review, early seizure manifestations were studied in 101 patients with supratentorial grade 2 gliomas subjected to MET PET as part of the pretreatment tumour investigation. Seizure manifestations as a variable was then used in multivariate survival analyses, together with established prognostic factors for this patient group.

Results

Of all 101 cases, 88 patients had seizures at tumour presentation. Fortyseven were seizure free at the early stage of the disease, whereas 54 had recurrent seizures. Patients with seizures at tumour presentation had a more favourable outcome before and after (P = 0.006) adjustment for conventional prognostic factors. However, for those who continued to have seizures early in the disease, the outcome was worse (P = 0.003). We found no significant correlation between MET PET and the seizure manifestations of the patients.

Conclusion

The presence and termination of early seizure manifestations may be favourable prognostic factors in patients with low-grade gliomas.

 

Place, publisher, year, edition, pages
2009. Vol. 16, no 7, 823-831 p.
Keyword [en]
11C methionine positron emission tomography, epileptic seizures, low-grade glioma, survival
National Category
Neurology
Research subject
Neurology
Identifiers
URN: urn:nbn:se:uu:diva-105434DOI: 10.1111/j.1468-1331.2009.02599.xISI: 000266637000012OAI: oai:DiVA.org:uu-105434DiVA: diva2:221235
Available from: 2009-06-03 Created: 2009-06-03 Last updated: 2017-12-13Bibliographically approved
In thesis
1. 11C Molecular Imaging in Focal Epilepsy
Open this publication in new window or tab >>11C Molecular Imaging in Focal Epilepsy
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Epilepsy is a common neurological disease affecting 6 million people in Europe. Early prevention and accurate diagnosis and treatment are of importance to obtain seizure freedom. In this thesis new applications of carbon-11-labelled tracers in PET and autoradiographic studies were explored in focal epilepsy.

Patients with low-grade gliomas often experience epileptic seizures. A retrospective PET-study assessing seizure activity, metabolic rate measured with 11C-methionine and other known prognostic factors was performed in patients with glioma. No correlation was found between seizure activity and uptake of methionine. The presence and termination of early seizures was a favourable prognostic factor.

Activation of the neurokinin-1 (NK1) receptor by substance P (SP) induces epileptic activity. PET with the NK1 receptor antagonist GR205171 was performed in patients with temporal lobe epilepsy (TLE) and healthy controls. In TLE patients an increased NK1 receptor availability was found in both hemispheres, most pronounced in anterior cingulate gyrus ipsilateral to seizure onset. A positive correlation between NK1 receptors and seizure frequency was observed in ipsilateral medial structures consistent with an intrinsic network using the NK1-SP receptor system for transmission of seizure activity.

The uptake of 18F-fluoro-deoxy-glucose (FDG) is related to cerebral blood flow (CBF). Previously, methods to estimate blood flow from dynamic PET data have been described. A retrospective study was conducted in 15 patients undergoing epilepsy surgery investigation, including PET with 11C-FDG and 11C-Flumazenil (FMZ). The dynamic FMZ dataset and pharmacokinetic modeling with a multilinear reference tissue model were used to determine images of relative CBF. Agreement between data of FDG and CBF was analyzed showing a close association between interictal brain metabolism and relative CBF.

Epilepsy often occurs after traumatic brain injuries. Changes in glia and inhibitory neuronal cells contribute to the chain of events leading to seizures. Autoradiography with 11C-PK11195, 11C-L-deprenyl and 11C-Flumazenil in an animal model of posttraumatic epilepsy studied the temporal and spatial distribution of microglia, astrocytes and GABAergic neurons. Results showed an instant increase in microglial activity that subsequently normalized, a late formation of astrogliosis and an instant and prolonged decease in GABA binding. The model can be used to visualize pathophysiological events during the epileptogenesis.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 58 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 814
Keyword
positron emission tomography, methionine, NK1, substance p, flumazenil, deprenyl, pk11195, phosphoimager, autoradiography, TBI, traumatic brain injury, iron chloride, ferrous chloride
National Category
Neurology Radiology, Nuclear Medicine and Medical Imaging
Research subject
Neurology; Radiology
Identifiers
urn:nbn:se:uu:diva-179954 (URN)978-91-554-8475-0 (ISBN)
Public defence
2012-10-26, Enghoff salen, Akademiska sjukhuset, ing 50, bv, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2012-10-04 Created: 2012-08-27 Last updated: 2013-01-23Bibliographically approved
2. Towards Novel Biomarkers for Low-grade Glioma
Open this publication in new window or tab >>Towards Novel Biomarkers for Low-grade Glioma
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Gliomas are common primary brain tumours that occur as low-grade (LGG) and high-grade gliomas (HGG). Typically occurring in younger adults, LGG has an indolent course with a median survival of 5-10 years, but carries an inherent potential for transforming into HGG. The thesis focused on LGG in adults, with the aim of identifying prognostic biomarkers for LGG.

Paper I. Epileptic seizures are common symptoms in LGG. In a retrospective study, the correlation between 11C-methionine (MET) uptake, measured by Positron Emission Tomography (PET), and seizure activity was assessed in 101 patients with LGG. Although there was no correlation between MET uptake and seizure activity, survival was longer in patients who were seizure-free before surgery.

Paper II. This finding prompted the search for common genetic pathways for both tumour and seizure development and a review of genetic polymorphisms in focal epilepsy and glioma risk. Cell cycle and immune response genes affecting both glioma and seizure risk were identified, and genes involved in synaptic transmission presented potential candidates for future studies.

Paper III. The transcription factor PROX1 plays a pivotal role in normal development and carcinogenesis of various organs. The prognostic value of PROX1, together with established clinical and molecular prognostic factors for survival, was retrospectively assessed in 116 patients with LGG. High PROX1 expression in the tumour was associated with shorter survival.

Paper IV. DNA repair enzymes, such as ERCC6, are crucial for maintaining genomic stability in glioma response to radiotherapy. An association between the polymorphism rs4253079, mapped to ERCC6, and longer survival in patients with LGG and HGG was identified.

Paper V. As LGG typically presented as non-contrast enhancing tumours on morphological MRI (magnetic resonance imaging), the value of combined MET PET with physiological MRI for preoperative diagnosis was assessed in a prospective study of 32 patients with suspected LGG. Representative tumour areas were identified through a combination of perfusion-MRI with MET PET, which can be used as a baseline investigation for follow-up over time.

Conclusions: The parameters seizure-freedom before surgery, the polymorphism rs4253079 in ERCC6 and low PROX1 expression in the tumor were identified as favorable prognostic biomarkers.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 70 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 834
Keyword
Low-grade glioma, prognosis, epilepsy, PROX1, DNA repair enzyme, PET, Physiological MRI
National Category
Medical and Health Sciences
Research subject
Neuroscience
Identifiers
urn:nbn:se:uu:diva-183363 (URN)978-91-554-8518-4 (ISBN)
Public defence
2012-12-10, Rosénsalen, Akademiska sjukhuset, ing. 95, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2012-11-19 Created: 2012-10-24 Last updated: 2013-01-23Bibliographically approved

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Danfors, TorstenBerntsson, Shala G.Smits, Anja

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