Kuriko Kagitani-Shimono1,2,3, Hiroki Kato4, Ryoko Kuwayama5,6, Koji Tominaga7,5,6, Shin Nabatame5,6, Haruhiko Kishima6,8, Jun Hatazawa4,9, Masako Taniike7,5. 1. Department of Child Development, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan. kuriko@ped.med.osaka-u.ac.jp. 2. Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan. kuriko@ped.med.osaka-u.ac.jp. 3. Epilepsy Center, Osaka University Hospital, Suita, Japan. kuriko@ped.med.osaka-u.ac.jp. 4. Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Suita, Japan. 5. Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan. 6. Epilepsy Center, Osaka University Hospital, Suita, Japan. 7. Department of Child Development, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan. 8. Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan. 9. Department of Quantum Cancer Therapy Research Center for Nuclear Physics, Osaka University, Suita, Japan.
Abstract
BACKGROUND: Neuroinflammation is associated with various chronic neurological diseases, including epilepsy; however, neuroimaging approaches for visualizing neuroinflammation have not been used in the clinical routine yet. In this study, we used the translocator protein positron emission tomography (PET) with [11C] DPA713 to investigate neuroinflammation in the epileptogenic zone in patients with child-onset focal epilepsy. METHODS: Patients with intractable focal epilepsy were recruited at the Epilepsy Center of Osaka University; those who were taking any immunosuppressants or steroids were excluded. PET images were acquired for 60 min after intravenous administration of [11C] DPA713. The PET image of [11C] DPA713 was co-registered to individual's magnetic resonance imaging (MRI), and the standardized uptake value ratio (SUVr) in regions of interest, which were created in non-lesions and lesions, was calculated using the cerebellum as a pseudo-reference region. In the case of epilepsy surgery, the correlation between SUVr in lesions and pathological findings was analyzed. RESULTS: Twenty-seven patients (mean age: 11.3 ± 6.2 years, male/female: 17/10) were included in this study. Of these, 85.1% showed increased uptake of [11C] DPA713 in the focal epileptic lesion. Three patients showed epileptic spasms, suggesting partial seizure onset, and all 18 patients with abnormal lesions on MRI were similarly highlighted by significant uptake of [11C] DPA713. DPA713-positive patients had a broad range of etiologies, including focal cortical dysplasia, tumors, infarction, and hippocampal sclerosis. Five out of nine MRI-negative patients showed abnormal [11C] DPA713 uptake. The SUVr of [11C] DPA713 in lesions was significantly higher than that in non-lesions. In seven patients who underwent epilepsy surgery, increased [11C] DPA713 uptake was associated with microglial activation. CONCLUSIONS: This study indicates that [11C] DPA713 uptake has valuable sensitivity in the identification of epileptic foci in child-onset focal epilepsy, and inflammation is implicated in the pathophysiology in the epileptic foci caused by various etiologies. Further research is required to establish diagnostic tools for identifying focal epileptogenic zones.
BACKGROUND: Neuroinflammation is associated with various chronic neurological diseases, including epilepsy; however, neuroimaging approaches for visualizing neuroinflammation have not been used in the clinical routine yet. In this study, we used the translocator protein positron emission tomography (PET) with [11C] DPA713 to investigate neuroinflammation in the epileptogenic zone in patients with child-onset focal epilepsy. METHODS:Patients with intractable focal epilepsy were recruited at the Epilepsy Center of Osaka University; those who were taking any immunosuppressants or steroids were excluded. PET images were acquired for 60 min after intravenous administration of [11C] DPA713. The PET image of [11C] DPA713 was co-registered to individual's magnetic resonance imaging (MRI), and the standardized uptake value ratio (SUVr) in regions of interest, which were created in non-lesions and lesions, was calculated using the cerebellum as a pseudo-reference region. In the case of epilepsy surgery, the correlation between SUVr in lesions and pathological findings was analyzed. RESULTS: Twenty-seven patients (mean age: 11.3 ± 6.2 years, male/female: 17/10) were included in this study. Of these, 85.1% showed increased uptake of [11C] DPA713 in the focal epileptic lesion. Three patients showed epileptic spasms, suggesting partial seizure onset, and all 18 patients with abnormal lesions on MRI were similarly highlighted by significant uptake of [11C] DPA713. DPA713-positive patients had a broad range of etiologies, including focal cortical dysplasia, tumors, infarction, and hippocampal sclerosis. Five out of nine MRI-negative patients showed abnormal [11C] DPA713 uptake. The SUVr of [11C] DPA713 in lesions was significantly higher than that in non-lesions. In seven patients who underwent epilepsy surgery, increased [11C] DPA713 uptake was associated with microglial activation. CONCLUSIONS: This study indicates that [11C] DPA713 uptake has valuable sensitivity in the identification of epileptic foci in child-onset focal epilepsy, and inflammation is implicated in the pathophysiology in the epileptic foci caused by various etiologies. Further research is required to establish diagnostic tools for identifying focal epileptogenic zones.
Authors: Carlos A Pardo; Eileen P G Vining; Liping Guo; Richard L Skolasky; Benjamin S Carson; John M Freeman Journal: Epilepsia Date: 2004-05 Impact factor: 5.864
Authors: Ingrid E Scheffer; Samuel Berkovic; Giuseppe Capovilla; Mary B Connolly; Jacqueline French; Laura Guilhoto; Edouard Hirsch; Satish Jain; Gary W Mathern; Solomon L Moshé; Douglas R Nordli; Emilio Perucca; Torbjörn Tomson; Samuel Wiebe; Yue-Hua Zhang; Sameer M Zuberi Journal: Epilepsia Date: 2017-03-08 Impact factor: 5.864
Authors: Martin Wirenfeldt; Ryan Clare; Spencer Tung; Alexander Bottini; Gary W Mathern; Harry V Vinters Journal: Neurobiol Dis Date: 2009-03-10 Impact factor: 5.996
Authors: Anthony K Ngugi; Christian Bottomley; Immo Kleinschmidt; Josemir W Sander; Charles R Newton Journal: Epilepsia Date: 2010-01-07 Impact factor: 5.864