Skip to main content Accessibility help
  • Print publication year: 2019
  • Online publication date: January 2019

Chapter 9 - Mapping Metabolism and Inflammation in Epilepsy

from Part II - Modeling Epileptogenic Lesions and Mapping Networks
1.Vezzani, A, Granata, T. Brain inflammation in epilepsy: experimental and clinical evidence. Epilepsia. 2005;46:1724–43.
2.Marchi, N, Granata, T, Janigro, D. Inflammatory pathways of seizure disorders. Trends Neurosci. 2014;37:5565.
3.Otáhal, J, Folbergrová, J, Kovacs, R, et al. Epileptic focus and alteration of metabolism. Int Rev Neurobiol. 2014;114:209–43.
4.Kuhl, DE, Engel, J Jr, Phelps, ME, et al. Epileptic patterns of local cerebral metabolism and perfusion in humans determined by emission computed tomography of 18FDG and 13NH3. Ann Neurol. 1980;8:348–60.
5.Mazziotta, JC, Engel, J Jr. The use and impact of positron computed tomography scanning in epilepsy. Epilepsia. 1984;25(suppl 2):S86104.
6.Johnson, EW, de Lanerolle, NC, Kim, JH, et al. “Central” and “peripheral” benzodiazepine receptors: opposite changes in human epileptogenic tissue. Neurology. 1992;42:811–5.
7.Kumlien, E, Hilton-Brown, P, Spännare, B, et al. In vitro quantitative autoradiography of [3H]-L-deprenyl and [3H]-PK11195 binding sites in human epileptic hippocampus. Epilepsia. 1992;33:610–7.
8.Vezzani, A, French, J, Bartfai, T, et al. The role of inflammation in epilepsy. Nat Rev Neurol. 2011;7:3140.
9.Amhaoul, H, Staelens, S, Dedeurwaerdere, S. Imaging brain inflammation in epilepsy. Neuroscience. 2014;279:238–52.
10.O’Brien, TJ, Jupp, B. In-vivo imaging with small animal FDG-PET: a tool to unlock the secrets of epileptogenesis? Exp Neurol. 2009;220:14.
11.Pitkänen, A, Lukasiuk, K. Mechanisms of epileptogenesis and potential treatment targets. Lancet Neurol. 2011;10:173–86.
12.Engel, J Jr, Pitkanen, A, Loeb, JA, et al. Epilepsy biomarkers. Epilepsia. 2013;54(suppl 4):61–9.
13.Guo, Y, Gao, F, Wang, S, et al. In vivo mapping of temporospatial changes in glucose utilization in rat brain during epileptogenesis: an 18F-fluorodeoxyglucose-small animal positron emission tomography study. Neuroscience. 2009;162:972–9.
14.Lee, EM, Park, GY, Im, KC, et al. Changes in glucose metabolism and metabolites during the epileptogenic process in the lithium-pilocarpine model of epilepsy. Epilepsia. 2012;53:860–9.
15.Jupp, B, Williams, B, Binns, D, et al. Hypometabolism precedes limbic atrophy and spontaneous recurrent seizures in a rat model of TLE. Epilepsia. 2012;53:1233–44.
16.Shultz, SR, Cardamone, L, Liu, YR, et al. Can structural or functional changes following traumatic brain injury in the rat predict epileptic outcome? Epilepsia. 2013;54:1240–50.
17.Benedek, K, Juhász, C, Muzik, O, et al. Metabolic changes of subcortical structures in intractable focal epilepsy. Epilepsia. 2004;45:1100–5.
18.Keller, SS, O’Muircheartaigh, J, Traynor, C, Towgood, K, Barker, GJ, Richardson, MP. Thalamotemporal impairment in temporal lobe epilepsy: a combined MRI analysis of structure, integrity, and connectivity. Epilepsia. 2014;55(2):306–15.
19.Camilo, O, Goldstein, LB. Seizures and epilepsy after ischemic stroke. Stroke. 2004;35:1769–75.
20.Lossius, MI, Rønning, OM, Slapø, GD, et al. Poststroke epilepsy: occurrence and predictors—a long-term prospective controlled study (Akershus Stroke Study). Epilepsia. 2005;46:1246–51.
21.Wang, H, Xin, T, Sun, X, et al. Post-traumatic seizures—a prospective, multicenter, large case study after head injury in China. Epilepsy Res. 2013;107:272–8.
22.Ville, D, Enjolras, O, Chiron, C, et al. Prophylactic antiepileptic treatment in Sturge-Weber disease. Seizure. 2002;11:145–50.
23.Jóźwiak, S, Kotulska, K, Domanska-Pakiela, D, et al. Antiepileptic treatment before the onset of seizures reduces epilepsy severity and risk of mental retardation in infants with tuberous sclerosis complex. Eur J Paediatr Neurol. 2011;15:424–31.
24.Alkonyi, B, Chugani, HT, Juhász, C. Transient focal increase of interictal glucose metabolism in Sturge-Weber syndrome: implications for epileptogenesis. Epilepsia. 2011;52:1265–72.
25.Chugani, HT, Mazziotta, JC, Phelps, ME. Sturge-Weber syndrome: a study of cerebral glucose utilization with positron emission tomography. J Pediatr. 1989; 114:244–53.
26.Juhász, C, Hu, J, Xuan, Y, Chugani, H. Imaging increased glutamate in children with Sturge-Weber syndrome: association with epilepsy severity. Epilepsy Res. 2016;122:6672.
27.Ashwal, S, Holshouser, B, Tong, K, et al. Proton MR spectroscopy detected glutamate/glutamine is increased in children with traumatic brain injury. J Neurotrauma. 2004;21:1539–52.
28.Gaillard, WD, Kopylev, L, Weinstein, S, et al. Low incidence of abnormal (18)FDG-PET in children with new-onset partial epilepsy: a prospective study. Neurology. 2002;58:717–22.
29.Weitemeyer, L, Kellinghaus, C, Weckesser, M, et al. The prognostic value of [18F]FDG-PET in nonrefractory partial epilepsy. Epilepsia. 2005;46:1654–60.
30.Gaillard, WD, Weinstein, S, Conry, J, et al. Prognosis of children with partial epilepsy: MRI and serial 18FDG-PET. Neurology. 2007;68:655–9.
31.Henry, TR. Positron emission tomography: glucose metabolism studies in temporal lobe epilepsy. In: Chugani, HT, ed. Neuroimaging in Epilepsy. New York: Oxford University Press; 2011:122–40.
32.Juhász, C, Chugani, HT. Positron emission tomography: glucose metabolism in extratemporal lobe epilepsy. In: Chugani, HT, ed. Neuroimaging in Epilepsy. New York: Oxford University Press; 2011:141–55.
33.Tenney, JR, Rozhkov, L, Horn, P, et al. Cerebral glucose hypometabolism is associated with mitochondrial dysfunction in patients with intractable epilepsy and cortical dysplasia. Epilepsia. 2014;55:1415–22.
34.Swartz, BE, Brown, C, Mandelkern, MA, et al. The use of 2-deoxy-2-[18F]fluoro-D-glucose (FDG-PET) positron emission tomography in the routine diagnosis of epilepsy. Mol Imaging Biol. 2002;4:245–52.
35.Benedek, K, Juhász, C, Chugani, DC, et al. Longitudinal changes in cortical glucose hypometabolism in children with intractable epilepsy. J Child Neurol. 2006;21:2631.
36.Juhász, C, Batista, CE, Chugani, DC, et al. Evolution of cortical metabolic abnormalities and their clinical correlates in Sturge-Weber syndrome. Eur J Paediatr Neurol. 2007;11:277–84.
37.Choi, JY, Kim, SJ, Hong, SB, et al. Extratemporal hypometabolism on FDG PET in temporal lobe epilepsy as a predictor of seizure outcome after temporal lobectomy. Eur J Nucl Med Mol Imaging. 2003;30:581–7.
38.Spanaki, MV, Kopylev, L, DeCarli, C, et al. Postoperative changes in cerebral metabolism in temporal lobe epilepsy. Arch Neurol. 2000;57:1447–52.
39.Joo, EY, Hong, SB, Han, HJ, et al. Postoperative alteration of cerebral glucose metabolism in mesial temporal lobe epilepsy. Brain. 2005;128(pt 8):1802–10.
40.Takaya, S, Mikuni, N, Mitsueda, T, et al. Improved cerebral function in mesial temporal lobe epilepsy after subtemporal amygdalohippocampectomy. Brain. 2009;132(pt 1):185–94.
41.Talanow, R, Ruggieri, P, Alexopoulos, A, et al. PET manifestation in different types of pathology in epilepsy. Clin Nucl Med. 2009;34:670–4.
42.Sarria-Estrada, S, Toledo, M, Lorenzo-Bosquet, C, et al. Neuroimaging in status epilepticus secondary to paraneoplastic autoimmune encephalitis. Clin Radiol. 2014;69:795803.
43.Dedeurwaerdere, S, Callaghan, PD, Pham, T, et al. PET imaging of brain inflammation during early epileptogenesis in a rat model of temporal lobe epilepsy. EJNMMI Res. 2012;2:60.
44.Van Camp, N, Boisgard, R, Kuhnast, B, et al. In vivo imaging of neuroinflammation: a comparative study between [(18)F]PBR111, [(11)C] CLINME and [(11)C]-PK11195 in an acute rodent model. Eur J Nucl Med Mol Imaging. 2010;37:962–72.
45.Bogdanović, RM, Syvänen, S, Michler, C, et al. (R)-[11C]PK11195 brain uptake as a biomarker of inflammation and antiepileptic drug resistance: evaluation in a rat epilepsy model. Neuropharmacology. 2014;85:104–12.
46.Banati, RB, Goerres, GW, Myers, R, et al. [11C](R)-PK11195 positron emission tomography imaging of activated microglia in vivo in Rasmussen’s encephalitis. Neurology. 1999;53:2199–203.
47.Kumar, A, Chugani, HT, Luat, A, et al. Epilepsy surgery in a case of encephalitis: use of 11C-PK11195 positron emission tomography. Pediatr Neurol. 2008;38:439–42.
48.Kreisl, WC, Fujita, M, Fujimura, Y, et al. Comparison of [11C]-(R)-PK11195 and [11C]PBR28, two radioligands for translocator protein (18 kDa) in human and monkey: Implications for positron emission tomographic imaging of this inflammation biomarker. NeuroImage. 2010;49:2924–32.
49.Butler, T, Ichise, M, Teich, AF, et al. Imaging inflammation in a patient with epilepsy due to focal cortical dysplasia. J Neuroimaging. 2013;23:129–31.
50.Hirvonen, J, Kreisl, WC, Fujita, M, et al. Increased in vivo expression of an inflammatory marker in temporal lobe epilepsy. J Nucl Med. 2012;53:234–40.
51.Nash, TE, Mahanty, S, Loeb, JA, et al. Neurocysticercosis: A natural human model of epileptogenesis. Epilepsia. 2015;56:177–83.
52.Fujita, M, Mahanty, S, Zoghbi, SS, et al. PET reveals inflammation around calcified Taenia solium granulomas with perilesional edema. PLOS ONE. 2013;8:e74052.
53.Kaim, AH, Weber, B, Kurrer, MO, et al. 18F-FDG and 18F-FET uptake in experimental soft tissue infection. Eur J Nucl Med Mol Imaging. 2002;29:648–54.
54.Stöber, B, Tanase, U, Herz, M, et al. Differentiation of tumour and inflammation: characterisation of [methyl-3H]methionine (MET) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) uptake in human tumour and inflammatory cells. Eur J Nucl Med Mol Imaging. 2006;33:932–9.
55.Sasaki, M, Kuwabara, Y, Yoshida, T, et al. Carbon-11-methionine PET in focal cortical dysplasia: a comparison with fluorine-18-FDG PET and technetium-99m-ECD SPECT. J Nucl Med. 1998;39:974–7.
56.Madakasira, PV, Simkins, R, Narayanan, T, et al. Cortical dysplasia localized by [11C]methionine positron emission tomography: case report. AJNR Am J Neuroradiol. 2002;23:844–6.
57.Phi, JH, Paeng, JC, Lee, HS, et al. Evaluation of focal cortical dysplasia and mixed neuronal and glial tumors in pediatric epilepsy patients using 18F-FDG and 11C-methionine PET. J Nucl Med. 2010;51:728–34.
58.Diksic, M, Nagahiro, S, Sourkes, TL, et al. A new method to measure brain serotonin synthesis in vivo. I. Theory and basic data for a biological model. J Cereb Blood Flow Metab. 1990;10:112.
59.Diksic, M, Tohyama, Y, Takada, A. Brain net unidirectional uptake of alpha-[14C]methyl-L-tryptophan (alpha-MTrp) and its correlation with regional serotonin synthesis, tryptophan incorporation into proteins, and permeability surface area products of tryptophan and alpha-MTrp. Neurochem Res. 2000;25:1537–46.
60.Muzik, O, Chugani, DC, Chakraborty, P, et al. Analysis of [C-11]alpha-methyl-tryptophan kinetics for the estimation of serotonin synthesis rate in vivo. J Cereb Blood Flow Metab. 1997;17:659–69.
61.Trottier, S, Evrard, B, Vignal, JP, et al. The serotonergic innervation of the cerebral cortex in man and its changes in focal cortical dysplasia. Epilepsy Res. 1996;25:79106.
62.Chugani, DC, Muzik, O. Alpha[C-11]methyl-L-tryptophan PET maps brain serotonin synthesis and kynurenine pathway metabolism. J Cereb Blood Flow Metab. 2000;20:29.
63.Chugani, DC. Alpha-methyl-L-tryptophan: mechanisms for tracer localization of epileptogenic brain regions. Biomarkers Med. 2011; 5:567–75.
64.Feldblum, S, Rougier, A, Loiseau, H, et al. Quinolinic acid phosphoribosyl transferase activity is decreased in epileptic human brain tissue. Epilepsia. 1988;29:523–9.
65.Heyes, MP, Wyler, AR, Devinsky, O, et al. Quinolinic acid concentrations in brain and cerebrospinal fluid of patients with intractable complex partial seizures. Epilepsia. 1990;31:172–7.
66.Munn, DH, Mellor, AL. Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J Clin Invest. 2007;117:1147–54.
67.Pilotte, L, Larrieu, P, Stroobant, V, et al. Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase. Proc Natl Acad Sci USA. 2012;109:2497–502.
68.Vacchelli, E, Aranda, F, Eggermont, A, et al. Trial watch: IDO inhibitors in cancer therapy. Oncoimmunology. 2014;3:e957994.
69.Chugani, DC, Chugani, HT, Muzik, O, et al. Imaging epileptogenic tubers in children with tuberous sclerosis complex using alpha-[11C]methyl-L-tryptophan positron emission tomography. Ann Neurol. 1998;44:858–66.
70.Fedi, M, Reutens, DC, Andermann, F, et al. Alpha-[11C]-methyl-L-tryptophan PET identifies the epileptogenic tuber and correlates with interictal spike frequency. Epilepsy Res. 2003;52:203–13.
71.Rubí, S, Costes, N, Heckemann, RA, et al. Positron emission tomography with α-[11C]methyl-L-tryptophan in tuberous sclerosis complex-related epilepsy. Epilepsia. 201;54:2143–50.
72.Chugani, HT, Luat, AF, Kumar, A, et al. a-[11C]-Methyl-L- tryptophan PET in. 191 patients with tuberous sclerosis complex. Neurology. 2013;81:674–80.
73.Kagawa, K, Chugani, DC, Asano, E, et al. Epilepsy surgery outcome in children with tuberous sclerosis complex evaluated with alpha-[11C]methyl-L-tryptophan positron emission tomography (PET). J Child Neurol. 2005;20:429–38.
74.Fedi, M, Reutens, D, Okazawa, H, et al. Localizing value of alpha-methyl-L-tryptophan PET in intractable epilepsy of neocortical origin. Neurology. 2001;57:1629–36.
75.Juhász, C, Chugani, DC, Muzik, O, et al. Alpha-methyl-L-tryptophan PET detects epileptogenic cortex in children with intractable epilepsy. Neurology. 2003;60:960–8.
76.Chugani, HT, Kumar, A, Kupsky, W, et al. Clinical and histopathologic correlates of 11C-alpha-methyl-L-tryptophan (AMT) PET abnormalities in children with intractable epilepsy. Epilepsia. 2011;52:1692–8.
77.Natsume, J, Kumakura, Y, Bernasconi, N, et al. Alpha-[11C] methyl-L-tryptophan and glucose metabolism in patients with temporal lobe epilepsy. Neurology. 2003;60:756–61.
78.Asano, E, Chugani, DC, Muzik, O, et al. Multimodality imaging for improved detection of epileptogenic foci in tuberous sclerosis complex. Neurology. 2000;54:1976–84.
79.Alkonyi, B, Mittal, S, Zitron, I, et al. Increased tryptophan transport in epileptogenic dysembryoplastic neuroepithelial tumors. J Neurooncol. 2012;107:365–72.
80.Juhász, C, Chugani, DC, Muzik, O, et al. Decreased GABAA receptor binding and increased uptake of α[11C]methyl-L-tryptophan on PET can independently identify human epileptogenic cortex. Neurology. 2002;58(suppl 3):A150.
81.Ravizza, T, Boer, K, Redeker, S, et al. The IL-1beta system in epilepsy-associated malformations of cortical development. Neurobiol Dis. 2006;24:128–43.
82.Boer, K, Jansen, F, Nellist, M, et al. Inflammatory processes in cortical tubers and subependymal giant cell tumors of tuberous sclerosis complex. Epilepsy Res. 2008;78:721.
83.Iyer, A, Zurolo, E, Spliet, WG, et al. Evaluation of the innate and adaptive immunity in type I and type II focal cortical dysplasias. Epilepsia. 2010;51:1763–73.
84.Shu, HF, Zhang, CQ, Yin, Q, et al. Expression of the interleukin 6 system in cortical lesions from patients with tuberous sclerosis complex and focal cortical dysplasia type IIb. J Neuropathol Exp Neurol. 2010;69:838–49.
85.Juhász, C, Buth, A, Chugani, DC, et al. Successful surgical treatment of an inflammatory lesion associated with new-onset refractory status epilepticus. Neurosurg Focus. 2013b;34(6):E5.