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Part III - Predicting the Response to Therapeutic Interventions

Published online by Cambridge University Press:  07 January 2019

Edited by
Andrea Bernasconi ,
Neda Bernasconi  and
Matthias Koepp
Andrea Bernasconi
Affiliation:
Montreal Neurological Institute, McGill University
Neda Bernasconi
Affiliation:
Montreal Neurological Institute, McGill University
Matthias Koepp
Affiliation:
Institute of Neurology, University College London
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Imaging Biomarkers in Epilepsy , pp. 135 - 180
Publisher: Cambridge University Press
Print publication year: 2019

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References

References

Shorvon, SD. The etiologic classification of epilepsy. Epilepsia. 2011;52:1052–7.CrossRefGoogle ScholarPubMed
Giblin, KA, Blumenfeld, H. Is epilepsy a preventable disorder? New evidence from animal models. Neuroscience. 2010;16(3):253–75.Google ScholarPubMed
Banerjee, PN, Filippi, D, Allen Hauser, W. The descriptive epidemiology of epilepsy—a review. Epilepsy Res. 2009;85:31–45.Google Scholar
Blumenfeld, H. New strategies for preventing epileptogenesis: perspective and overview. Neurosci Lett. 2011;497(3):153–4.Google Scholar
Chahboune H, , Mishra, AM, DeSalvo, MN, et al. DTI abnormalities in anterior corpus callosum of rats with spike-wave epilepsy. NeuroImage. 2009;47(2):459–66.Google Scholar
Mishra, AM, Bai, X, Sanganahalli, BG, Waxman, SG. Decreased resting functional connectivity after traumatic brain injury in the rat. PLOS ONE. 2014;9(4):e95280.CrossRefGoogle ScholarPubMed
Van Luijtelaar, G, Mishra, AM, Edelbroek, P, et al. Anti-epileptogenesis: electrophysiology, diffusion tensor imaging and behavior in a genetic absence model. Neurobiol Dis. 2013;60:126–38.CrossRefGoogle Scholar
Blumenfeld, H, Klein, JP, Schridde, U, et al. Early treatment suppresses the development of spike-wave epilepsy in a rat model. Epilepsia. 2008;49(3):400–9.Google Scholar
Shorvon, SD. A history of neuroimaging in epilepsy 1909–2009. Epilepsia. 2009;50:39–49.CrossRefGoogle ScholarPubMed
Filler, AG. The history, development and impact of computed imaging in neurological diagnosis and neurosurgery: CT, MRI, and DTI. Nat Proc. 2009. Available at:http://precedings.nature.com/documents/3267/version/5.Google Scholar
Patterson, JL, Carapetian, SA, Hageman, JR, Kelley, KR. Febrile seizures. Pediatr Ann. 2013;42:249–54.Google Scholar
Dubé, C, Yu, H, Nalcioglu, O, Baram, TZ. Serial MRI after experimental febrile seizures: altered T2 signal without neuronal death. Ann Neurol. 2004;56(3):709–14.CrossRefGoogle ScholarPubMed
Dube, M, Ravizza, T, Hamamura, M, et al. Epileptogenesis provoked by prolonged experimental febrile seizures: mechanisms and biomarkers. J Neurosci. 2010;30(22):7484–94.CrossRefGoogle ScholarPubMed
Choy, M, Dubé, CM, Patterson, K, et al. Neurobiology of disease: a novel, noninvasive, predictive epilepsy biomarker with clinical potential. J Neurosci. 2014;34(26):8672–84.CrossRefGoogle Scholar
Pagni, CA, Zenga, F. Prevention and treatment of post-traumatic epilepsy. Expert Rev Neurother. 2006;6(8):1223–33.Google Scholar
Pitkänen, A, McIntosh, T. Animal models of post-traumatic epilepsy. J Neurotrauma. 2006;23(2):241–61.Google Scholar
Kharatishvili, I, Sierra, A, Immonen, RJ, Gröhn, OHJ, Pitkänen, A. Quantitative T2 mapping as a potential marker for the initial assessment of the severity of damage after traumatic brain injury in rat. Exp Neurol. 2009;217(1):154–64.Google Scholar
Immonen, RJ, Kharatishvili, I, Gröhn, H, Pitkänen, A, Gröhn, OHJ. Quantitative MRI predicts long-term structural and functional outcome after experimental traumatic brain injury. NeuroImage. 2009;45(1):1–9.Google Scholar
Roch, C, Leroy, C, Nehlig, A, Namer, IJ. Predictive value of cortical injury for the development of temporal lobe epilepsy in 21-day-old rats: an MRI approach using the lithium-pilocarpine model. Epilepsia. 2002;43(10):1129–36.CrossRefGoogle ScholarPubMed
van Eijsden, P, Notenboom, RGE, Wu, O, et al. In vivo 1H magnetic resonance spectroscopy, T2-weighted and diffusion-weighted MRI during lithium-pilocarpine-induced status epilepticus in the rat. Brain Res. 2004;1030(1):11–8.Google Scholar
Choy, M, Cheung, KK, Thomas, DL, Gadian, DG, Lythgoe, MF, Scott, RC. Quantitative MRI predicts status epilepticus-induced hippocampal injury in the lithium-pilocarpine rat model. Epilepsy Res. 2010;88 (2–3):221–30.Google Scholar
Roch, C, Leroy, C, Nehlig, A, Namer, IJ. Magnetic resonance imaging in the study of the lithium-pilocarpine model of temporal lobe epilepsy in adult rats. Epilepsia. 2002;43(4):325–35.CrossRefGoogle Scholar
Nairismägi, J, Gröhn, OHJ, Kettunen, MI, Nissinen, J, Kauppinen, RA, Pitkänen, A. Progression of brain damage after status epilepticus and its association with epileptogenesis: a quantitative MRI study in a rat model of temporal lobe epilepsy. Epilepsia. 2004;45(9):1024–34.Google Scholar
Jupp, B, Williams, JP, Tesiram, YA, Vosmansky, M, O’Brien, TJ. Hippocampal T2 signal change during amygdala kindling epileptogenesis. Epilepsia. 2006;47(1):41–6.Google Scholar
Ashburner, J, Friston, KJ. Voxel-based morphometry—the methods. NeuroImage. 2000;11(6 p. 1):805–21.Google Scholar
Maguire, EA, Gadian, DG, Johnsrude, IS, et al. Navigation-related structural change in the hippocampi of taxi drivers. Proc Natl Acad Sci USA. 2000;97(8):4398–403.Google Scholar
Wolf, OT, Dyakin, V, Patel A, et al. Volumetric structural magnetic resonance imaging (MRI) of the rat hippocampus following kainic acid (KA) treatment. Brain Res. 2002;934(2):87–96.CrossRefGoogle Scholar
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(7):1240–50.Google Scholar
Kharatishvili, I, Immonen, R, Gro, O, Pitka, A, Gröhn, O, Pitkänen, A. Quantitative diffusion MRI of hippocampus as a surrogate marker for post-traumatic epileptogenesis. Brain. 2007;130(130):3155–68.Google Scholar
Liu, YR, Cardamone, L, Hogan, RE, et al. Progressive metabolic and structural cerebral perturbations after traumatic brain injury: an in vivo imaging study in the rat. J Nucl Med. 2010;51(11):1788–95.CrossRefGoogle Scholar
Immonen, R, Kharatishvili, I, Gröhn, O, Pitkänen, A, Pitkanen, A. MRI biomarkers for post-traumatic epileptogenesis. J Neurotrauma. 2013;30:1305–9.Google Scholar
Gupta, RK, Cloughesy, TF, Sinha, U, et al. Relationships between choline magnetic resonance spectroscopy, apparent diffusion coefficient and quantitative histopathology in human glioma. J Neurooncol. 2000;50(3):215–26.Google Scholar
Mishra, AM, Gupta, RK, Jaggi, RS, et al. Role of diffusion-weighted imaging and in vivo proton magnetic resonance spectroscopy in the differential diagnosis of ring-enhancing intracranial cystic mass lesions. J Comput Assist Tomogr. 2004;28(4):540–7.CrossRefGoogle ScholarPubMed
Nagarajan, R, Sarma, MK, Thames, AD, Castellon, SA, Hinkin, CH, Thomas, MA. 2D MR spectroscopy combined with prior-knowledge fitting is sensitive to HCV-associated cerebral metabolic abnormalities. Int J Hepatol. 2012;2012:179365.Google Scholar
Filibian, M, Frasca, A, Maggioni, D, Micotti, E, Vezzani, A, Ravizza, T. In vivo imaging of glia activation using 1H-magnetic resonance spectroscopy to detect putative biomarkers of tissue epileptogenicity. Epilepsia. 2012;53(11):1907–16.Google Scholar
Duncan, J. Magnetic resonance spectroscopy. Epilepsia. 1996;37(7):598–605.Google Scholar
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(5):860–9.Google Scholar
Alvestad, S, Hammer, J, Qu, H, Håberg, A, Ottersen, OP, Sonnewald, U. Reduced astrocytic contribution to the turnover of glutamate, glutamine, and GABA characterizes the latent phase in the kainate model of temporal lobe epilepsy. J Cereb Blood Flow Metab. 2011;31(8):1675–86.Google Scholar
Kuhl, DE, Engel, J Jr, Phelps, ME KA. Epileptic patterns of local computed, cerebral metabolism and perfusion in man: investigation by emission tomography of 18F-fluorodeoxyglucose and 13N-ammonia. Trans Am Neurol Assoc. 1978;103:52–3.Google Scholar
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(1):60.Google Scholar
Jones, NC, Nguyen, T, Corcoran, NM, et al. Targeting hyperphosphorylated tau with sodium selenate suppresses seizures in rodent models. Neurobiol Dis. 2012;45(3):897–901.Google Scholar
Virdee, K, Cumming, P, Caprioli, D, et al. Applications of positron emission tomography in animal models of neurological and neuropsychiatric disorders. Neurosci Biobehav Rev. 2012;36(4):1188–216.Google Scholar
Jupp, B, Williams, J, Binns, D, et al. Hypometabolism precedes limbic atrophy and spontaneous recurrent seizures in a rat model of TLE. Epilepsia. 2012;53(7):1233–44.CrossRefGoogle Scholar
Goffin, K, Van, Paesschen W, Dupont, P, Van, Laere K. Longitudinal microPET imaging of brain glucose metabolism in rat lithium-pilocarpine model of epilepsy. Exp Neurol. 2009;217(1):205–9.CrossRefGoogle ScholarPubMed
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(4):972–9.Google Scholar
Ogawa, S, Menon, RS, Tank, DW, et al. Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model. Biophys J. 1993;64(3):803–12.Google Scholar
Blumenfeld, H. Functional MRI studies of animal models in epilepsy. Epilepsia. 2007;48:18–26.CrossRefGoogle ScholarPubMed
Hyder, F. Dynamic imaging of brain function. Methods Mol Biol. 2009;489:3–21.Google Scholar
Ogawa, SLT. Blood oxygen level dependent MRI of the brain: effects of seizure induced by kainic acid in the rat. Proc Soc Magn Reson Med. 1992;1:501.Google Scholar
Friston, KJ, Frith, CD, Liddle, PF, Frackowiak, RS. Functional connectivity: the principal-component analysis of large (PET) data sets. J Cereb Blood Flow Metab. 1993;13(1):5–14.Google Scholar
Biswal, B, Yetkin, FZ, Haughton, VM, Hyde, JS. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med. 1995;34(4):537–41.CrossRefGoogle ScholarPubMed
Basser, PJ, Pierpaoli, C. Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. J Magn Reson B. 1996;111(3):209–19.Google Scholar
Ranjan, P, Mishra, AM, Kale, R, Saraswat, VA, Gupta, RK. Cytotoxic edema is responsible for raised intracranial pressure in fulminant hepatic failure: in vivo demonstration using diffusion-weighted MRI in human subjects. Metab Brain Dis. 2005;20(3):181–92.Google Scholar
Kale, RA, Gupta, RK, Saraswat, VA, et al. Demonstration of interstitial cerebral edema with diffusion tensor MR imaging in type C hepatic encephalopathy. Hepatology. 2006;43(4):698–706.Google Scholar
Gupta, RK, Hasan, KM, Mishra, AM, et al. High fractional anisotropy in brain abscesses versus other cystic intracranial lesions. AJNR Am J Neuroradiol. 2005;26(5):1107–14.Google Scholar
Beaulieu, C. The basis of anisotropic water diffusion in the nervous system—a technical review. NMR Biomed. 2002;15(7–8):435–55.Google Scholar
Frey, L, Lepkin, A, Schickedanz, A, Huber, K, Brown, MS, Serkova, N. ADC mapping and T1-weighted signal changes on post-injury MRI predict seizure susceptibility after experimental traumatic brain injury. Neurol Res. 2014;36(1):26–37.Google Scholar
Jansen, JFA, Lemmens, EMP, Strijkers, GJ, et al. Short- and long-term limbic abnormalities after experimental febrile seizures. Neurobiol Dis. 2008;32(2):293–301.CrossRefGoogle Scholar
Wall, CJ, Kendall, EJ, Obenaus A. Rapid alterations in diffusion-weighted images with anatomic correlates in a rodent model of status epilepticus. Am J Neuroradiol. 2000;21(10):1841–52.Google Scholar
Sierra, A, Laitinen, T, Lehtimäki, K, Rieppo, L, Pitkänen, A, Gröhn, O. Diffusion tensor MRI with tract-based spatial statistics and histology reveals undiscovered lesioned areas in kainate model of epilepsy in rat. Brain Struct Funct. 2011;216(2):123–35.Google Scholar
Hippocampal, Nehlig A MRI and other structural biomarkers: experimental approach to epileptogenesis. Biomark Med. 2011;5(5):585–97.Google Scholar
Guo, JN, Kim, R, Chen, Y, et al. Impaired consciousness in patients with absence seizures investigated by functional MRI, EEG, and behavioural measures: a cross-sectional study. Lancet Neurol. 2016;15:1336–45.Google Scholar
Bai, X, Vestal, M, Berman, R, et al. Dynamic time course of typical childhood absence seizures: EEG, behavior, and functional magnetic resonance imaging. J Neurosci. 2010;30(17):5884–93.Google Scholar
Vega, C, Vestal, M, DeSalvo, M, et al. Differentiation of attention-related problems in childhood absence epilepsy. Epilepsy Behav. 2010;19(1):82–5.Google Scholar
Vega, C, Guo, J, Killory, B, et al. Symptoms of anxiety and depression in childhood absence epilepsy. Epilepsia. 2011;52(8):e70–4.Google Scholar
Bai X, , Guo J, , Killory B, , et al. Resting functional connectivity between the hemispheres in childhood absence epilepsy. Neurology. 2011;76(23):1960–7.Google ScholarPubMed
Killory, BD, Bai, X, Negishi, M, et al. Impaired attention and network connectivity in childhood absence epilepsy. NeuroImage. 2011;56:2209–17.Google Scholar
Blumenfeld, H, Klein, JP, Schridde, U, et al. Early treatment suppresses the development of spike-wave epilepsy in a rat. Epilepsia. 2008;49(3):400–9.Google Scholar
Mishra, AM, Bai, X, Motelow, JE, et al. Increased resting functional connectivity in spike-wave epilepsy in WAG/Rij rats. Epilepsia. 2013;54(7):1214–22.Google Scholar
Klein, JP, Khera, DS, Nersesyan, H, Kimchi, EY, Waxman, SG, Blumenfeld, H. Dysregulation of sodium channel expression in cortical neurons in a rodent model of absence epilepsy. Brain Res. 2004;1000(1–2):102–9.Google Scholar
Blumenfeld H, , Lampert A, , Klein, JP, et al. Role of hippocampal sodium channel Nav1.6 in kindling epileptogenesis. Epilepsia. 2009;50(1):44–55.CrossRefGoogle ScholarPubMed
Dezsi, G, Ozturk, E, Stanic, D, et al. Ethosuximide reduces epileptogenesis and behavioral comorbidity in the GAERS model of genetic generalized epilepsy. Epilepsia. 2013;54(4):635–43.CrossRefGoogle ScholarPubMed
Berg, AT, Levy, SR, Testa, FM, Blumenfeld, H. Long-term seizure remission in childhood absence epilepsy: might initial treatment matter? Epilepsia. 2014;55(4):551–7.Google Scholar
Yasuda, CL, Betting, LE, Cendes, F. Voxel-based morphometry and epilepsy. Expert Rev Neurother. 2010;10(6):975–84.Google Scholar
Bruggemann, JM, Wilke, M, Som, SS, Bye, AME, Bleasel, A, Lawson, JA. Voxel-based morphometry in the detection of dysplasia and neoplasia in childhood epilepsy: Limitations of grey matter analysis. J Clin Neurosci. 2009;16(6):780–5.Google Scholar
Henley, S, Ridgway, GR, Scahill, RI, Kassubek, J. Pitfalls in the use of voxel-based morphometry as a biomarker: examples from Huntington. Am J Neuroradiol. 2010;31:711–9.CrossRefGoogle ScholarPubMed
Nersesyan, H, Hyder, F, Rothman, DL, Blumenfeld, H. Dynamic fMRI and EEG recordings during spike-wave seizures and generalized tonic-clonic seizures in WAG/Rij Rats. J Cereb Blood Flow Metab. 2004;24:589–99.Google Scholar
Mishra, AM, Ellens, DJ, Schridde, U, et al. Where fMRI and electrophysiology agree to disagree: corticothalamic and striatal activity patterns in the WAG/Rij rat. J Neurosci. 2011;31(42):15053–64.Google Scholar
Meeren, HKM, Pijn, JPM, Van Luijtelaar, ELJM, Coenen, AML, Lopes da Silva, FH. Cortical focus drives widespread corticothalamic networks during spontaneous absence seizures in rats. J Neurosci. 2002;22(4):1480–95.Google Scholar
Nersesyan, H, Herman, P, Erdogan, E, Hyder, F, Blumenfeld, H. Relative changes in cerebral blood flow and neuronal activity in local microdomains during generalized seizures. J Cereb Blood Flow Metab. 2004;1057–68.Google Scholar
Tenney, J, Duong, T, King, J. Corticothalamic modulation during absence seizures in rats: a functional MRI assessment. Epilepsia. 2003;44(9):1133–40.Google Scholar
Schridde, U, Khubchandani, M, Motelow, JE, Sanganahalli, BG, Hyder, F, Blumenfeld, H. Negative BOLD with large increases in neuronal activity. Cereb Cortex. 2008;18(8):1814–27.Google Scholar
DeSalvo, MN, Schridde, U, Mishra, AM, et al. Focal BOLD fMRI changes in bicuculline-induced tonic-clonic seizures in the rat. NeuroImage. 2010;50(3):902–9.CrossRefGoogle ScholarPubMed
Gotman, J, Grova, C, Bagshaw, A, Kobayashi, E, Aghakhani, Y, Dubeau, F. Generalized epileptic discharges show thalamocortical activation and suspension of the default state of the brain. Proc Natl Acad Sci USA. 2005;102(42):15236–40.Google Scholar
Hamandi, K, Laufs, H, Nöth, U, Carmichael, DW, Duncan, JS, Lemieux, L. BOLD and perfusion changes during epileptic generalised spike wave activity. NeuroImage. 2008;39(2):608–18.Google Scholar
Labate, A, Briellmann, RS, Abbott, DF, Waites, AB, Jackson, GD. Typical childhood absence seizures are associated with thalamic activation. Epileptic Disord. 2005;7(4):373–7.Google Scholar
Biswal, B, Yetkin, FZ, Haughton, VM, Hyde, JS. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med. 1995;34(4):537–41.Google Scholar
Waites, AB, Briellmann, RS, Saling, MM, Abbott, DF, Jackson, GD. Functional connectivity networks are disrupted in left temporal lobe epilepsy. Ann Neurol. 2006;59:335–43.Google Scholar
Muroi, J, Okuno, T, Kuno, C, et al. An MRI study of the myelination pattern in West syndrome. Brain Dev. 1996;18:179–84.Google Scholar
Schropp, C, Staudt, M, Staudt, F, et al. Delayed myelination in children with West syndrome: an MRI-study. Neuropediatrics. 1994;25:116–20.Google Scholar
Boska, MD, Hasan, KM, Kibuule, D, et al. Quantitative diffusion tensor imaging detects dopaminergic neuronal degeneration in a murine model of Parkinson’s disease. Neurobiol Dis. 2007;26(3):590–6.Google Scholar
Obenaus, A, Jacobs, RE. Magnetic resonance imaging of functional anatomy: use for small animal epilepsy models. Epilepsia. 2007;48(2002):11–7.Google Scholar
Song, S-K, Kim, JH, Lin, S-J, Brendza, RP, Holtzman, DM. Diffusion tensor imaging detects age-dependent white matter changes in a transgenic mouse model with amyloid deposition. Neurobiol Dis. 2004;15(3):640–7.Google Scholar
Gulani, V, Webb, AG, Duncan, ID, Lauterbur, PC. Apparent diffusion tensor measurements in myelin-deficient rat spinal cords. Magn Reson Med. 2001;45(2):191–5.Google Scholar
Harsan, LA, Poulet, P, Guignard, B, et al. Brain dysmyelination and recovery assessment by noninvasive in vivo diffusion tensor magnetic resonance imaging. J Neurosci Res. 2006;83(3):392–402.Google Scholar
Concha, L, Livy, D, Gross, D, Wheatley, B, Beaulieu, C. Direct correlation between diffusion tensor imaging and electron microscopy of the fornix in humans with temporal lobe epilepsy. Proc 16th Sci Meet Int Soc Magn Reson Med. 2008;566.Google Scholar
Hui, ES, Fu, QL, So, KF, Wu, EX. Diffusion tensor MR study of optic nerve degeneration in glaucoma. Proc Annu Int Conf IEEE Eng Med Biol. 2007;4312–5.Google Scholar

References

Brodie, MJ, Barry, SJE, Bamagous, GA, Norrie, JD, Kwan, P. Patterns of treatment response in newly diagnosed epilepsy. Neurology. 2012;78(20):1548–54.Google Scholar
Löscher, W, Klitgaard, H, Twyman, RE, Schmidt, D. New avenues for anti-epileptic drug discovery and development. Nat Rev Drug Discov. 2013;12(10):757–76.Google Scholar
Berg, AT, Berkovic, SF, Brodie, MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia. 2010;51(4):676–85.CrossRefGoogle ScholarPubMed
Kwan, P, Arzimanoglou, A, Berg, AT, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc task force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51(6):1069–77.Google Scholar
Löscher, W. Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs. Seizure. 2011;20(5):359–68.Google Scholar
Potschka, H. Animal models of drug-resistant epilepsy. Epileptic Disord. 2012;14(3):226–34.Google Scholar
Barton, ME, Klein, BD, Wolf, HH, White, HS. Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy. Epilepsy Res. 2001;47(3):217–27.Google Scholar
Srivastava, AK, White, HS. Carbamazepine, but not valproate, displays pharmacoresistance in lamotrigine-resistant amygdala kindled rats. Epilepsy Res. 2013;104(1–2):26–34.Google Scholar
Smyth, MD, Barbaro, NM, Baraban, SC. Effects of antiepileptic drugs on induced epileptiform activity in a rat model of dysplasia. Epilepsy Res. 2002;50(3):251–64.Google Scholar
Löscher, W. Animal models of drug-refractory epilepsy. In: Pitkänen, A, Schwartzkroin, P, Moshé, S, eds. Models of Seizures and Epilepsy. New York: Academic Press; 2006:551–67.Google Scholar
Löscher, W, Rundfeldt, C. Kindling as a model of drug-resistant partial epilepsy—selection of phenytoin-resistant and nonresistant rats. J Pharmacol Exp Ther. 1991;258(2):483–9.Google Scholar
Bankstahl, M, Bankstahl, JP, Löscher, W. Inter-individual variation in the anticonvulsant effect of phenobarbital in the pilocarpine rat model of temporal lobe epilepsy. Exp Neurol. 2012;234(1):70–84.CrossRefGoogle ScholarPubMed
Brandt, C, Volk, HA, Löscher, W. Striking differences in individual anticonvulsant response to phenobarbital in rats with spontaneous seizures after status epilepticus. Epilepsia. 2004;45(12):1488–97.Google Scholar
Glien, M, Brandt, C, Potschka, H, Löscher, W. Effects of the novel antiepileptic drug levetiracetam on spontaneous recurrent seizures in the rat pilocarpine model of temporal lobe epilepsy. Epilepsia. 2002;43(4):350–7.Google Scholar
Löscher, W. Mechanisms of drug resistance. Epileptic Disord. 2005;7(suppl 1):3–9.Google Scholar
Potschka, H, Brodie, MJ. Pharmacoresistance. Handbook Clin Neurol. 2012;108:741–57.Google Scholar
Remy, S, Gabriel, S, Urban, BW, et al. A novel mechanism underlying drug resistance in chronic epilepsy. Ann Neurol. 2003;53(4):469–79.Google Scholar
Remy, S, Urban, BW, Elger, CE, Beck, H. Anticonvulsant pharmacology of voltage-gated Na+ channels in hippocampal neurons of control and chronically epileptic rats. Eur J Neurosci. 2003;17(12):2648–58.Google Scholar
Ellerkmann, RK, Remy, S, Chen, J, et al. Molecular and functional changes in voltage-dependent Na+ channels following pilocarpine-induced status epilepticus in rat dentate granule cells. Neuroscience. 2003;119(2):323–33.Google Scholar
Brooks-Kayal, AR, Shumate, MD, Jin, H, Rikhter, TY, Coulter, DA. Selective changes in single cell GABA(A) receptor subunit expression and function in temporal lobe epilepsy. Nat Med. 1998;4(10):1166–72.Google Scholar
Coulter, DA. Mossy fiber zinc and temporal lobe epilepsy: pathological association with altered “epileptic” gamma-aminobutyric acid A receptors in dentate granule cells. Epilepsia. 2000;41:S96–9.Google Scholar
Volk, HA, Arabadzisz, D, Fritschy, JM, Brandt, C, Bethmann, K, Löscher, W. Antiepileptic drug-resistant rats differ from drug-responsive rats in hippocampal neurodegeneration and GABA(A) receptor ligand binding in a model of temporal lobe epilepsy. Neurobiol Dis. 2006;21(3):633–46.Google Scholar
Löscher, W, Potschka, H. Drug resistance in brain diseases and the role of drug efflux transporters. Nat Rev Neurosci. 2005;6(8):591–602.Google Scholar
Zhang, C, Kwan, P, Zuo, Z, Baum, L. The transport of antiepileptic drugs by P-glycoprotein. Adv Drug Deliv Rev. 2012;64(10):930–42.Google Scholar
Kwan, P, Brodie, MJ. Potential role of drug transporters in the pathogenesis of medically intractable epilepsy. Epilepsia. 2005;46(2):224–35.Google Scholar
Potschka, H, Volk, HA, Löscher, W. Pharmacoresistance and expression of multidrug transporter P-glycoprotein in kindled rats. NeuroReport. 2004;15(10):1657–61.Google Scholar
Tishler, DM, Weinberg, KI, Hinton, DR, Barbaro, N, Annett, GM, Raffel, C. Mdr1 gene-expression in brain of patients with medically intractable epilepsy. Epilepsia. 1995;36(1):1–6.Google Scholar
Volk, HA, Löscher, W. Multidrug resistance in epilepsy: rats with drug-resistant seizures exhibit enhanced brain expression of P-glycoprotein compared with rats with drug-responsive seizures. Brain. 2005;128:1358–68.Google Scholar
Brandt, C, Bethmann, K, Gastens, AM, Löscher, W. The multidrug transporter hypothesis of drug resistance in epilepsy: proof-of-principle in a rat model of temporal lobe epilepsy. Neurobiol Dis. 2006;24(1):202–11.Google Scholar
van Vliet, EA, van Schaik, R, Edelbroek, PM, et al. Inhibition of the multidrug transporter P-glycoprotein improves seizure control in phenytoin-treated chronic epileptic rats. Epilepsia. 2006;47(4):672–80.Google Scholar
Löscher, W, Langer, O. Imaging of P-glycoprotein function and expression to elucidate mechanisms of pharmacoresistance in epilepsy. Curr Top Med Chem. 2010;10(17):1785–91.Google Scholar
Syvänen, S, Eriksson, J. Advances in PET imaging of P-glycoprotein function at the blood-brain barrier. ACS Chem Neurosci. 2013;4(2):225–37.Google Scholar
Bankstahl, JP. What does a picture tell? In vivo imaging of ABC transporter function. Drug Discov Today Technol. 2014;12:e113–9.Google Scholar
Hendrikse, NH, Schinkel, AH, De Vries, EGE, et al. Complete in vivo reversal of P-glycoprotein pump function in the blood-brain barrier visualized with positron emission tomography. Br J Pharmacol. 1998;124(7):1413–8.Google Scholar
Luurtsema, G, Molthoff, CFM, Windhorst, AD, et al. (R)- and (S)-[C-11]verapamil as PET-tracers for measuring P-glycoprotein function: in vitro and in vivo evaluation. Nucl Med Biol. 2003;30(7):747–51.Google Scholar
Passchier, J, van Waarde, A, Doze, P, Elsinga, PH, Vaalburg, W. Influence of P-glycoprotein on brain uptake of [18F]MPPF in rats. Eur J Pharmacol. 2000;407(3):273–80.Google Scholar
Lazarova, N, Zoghbi, SS, Hong, J, et al. Synthesis and evaluation of [N-methyl-C-11]N-desmethyl-loperamide as a new and improved PET radiotracer for imaging P-gp function. J Med Chem. 2008;51(19):6034–43.Google Scholar
Bankstahl, JP, Kuntner, C, Abrahim, A, et al. Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-C-11-verapamil and PET. J Nucl Med. 2008;49(8):1328–35.Google Scholar
Farwell, MD, Chong, DJ, Iida, Y, Bae, SA, Easwaramoorthy, B, Ichise, M. Imaging P-glycoprotein function in rats using C-11-N-desmethyl-loperamide. Ann Nucl Med. 2013;27(7):618–24.Google Scholar
Tournier, N, Cisternino, S, Peyronneau, MA, et al. Discrepancies in the P-glycoprotein-mediated transport of F-18-MPPF: a pharmacokinetic study in mice and non-human primates. Pharm Res. 2012;29(9):2468–76.Google Scholar
Mairinger, S, Bankstahl, JP, Kuntner, C, et al. The antiepileptic drug mephobarbital is not transported by P-glycoprotein or multidrug resistance protein 1 at the blood-brain barrier: a positron emission tomography study. Epilepsy Res. 2012;100(1–2):93–103.Google Scholar
Verbeek, J, Eriksson, J, Syvanen, S, et al. 11C phenytoin revisited: synthesis by 11C CO carbonylation and first evaluation as a P-gp tracer in rats. EJNMMI Res. 2012;2(1):36.Google Scholar
Sander, K, Galante, E, Gendron, T, et al. Development of fluorine-18 labeled metabolically activated tracers for imaging of drug efflux transporters with positron emission tomography. J Med Chem. 2015;58(15):6058–80.Google Scholar
Bankstahl, JP, Bankstahl, M, Kuntner, C, et al. A novel positron emission tomography imaging protocol identifies seizure-induced regional overactivity of P-glycoprotein at the blood-brain barrier. J Neurosci. 2011;31(24):8803–11.Google Scholar
Kuntner, C, Bankstahl, JP, Bankstahl, M, et al. Dose-response assessment of tariquidar and elacridar and regional quantification of P-glycoprotein inhibition at the rat blood-brain barrier using (R)-[11C]verapamil PET. Eur J Nucl Med Mol Imaging. 2010;37(5):942–53.Google Scholar
Bauer, M, Zeitlinger, M, Karch, R, et al. Pgp-mediated interaction between (R)-C-11 verapamil and tariquidar at the human blood-brain barrier: a comparison with rat data. Clin Pharmacol Ther. 2012;91(2):227–33.Google Scholar
Feldmann, M, Asselin, MC, Liu, J, et al. P-glycoprotein expression and function in patients with temporal lobe epilepsy: a case-control study. Lancet Neurol. 2013;12(8):777–85.Google Scholar
Moerman, L, Wyffels, L, Slaets, D, Raedt, R, Boon, P, De Vos, F. Antiepileptic drugs modulate P-glycoproteins in the brain: A mice study with 11C-desmethylloperamide. Epilepsy Res. 2011;94(1–2):18–25.Google Scholar
Martin, C, Berridge, G, Mistry, P, Higgins, C, Charlton, P, Callaghan, R. The molecular interaction of the high affinity reversal agent XR9576 with P-glycoprotein. Br J Pharmacol. 1999;128(2):403–11.Google Scholar
Bankstahl, JP, Bankstahl, M, Römermann, K, et al. Tariquidar and elacridar are dose-dependently transported by P-glycoprotein and Bcrp at the blood-brain barrier: a small-animal positron emission tomography and in vitro study. Drug Metab Dispos. 2013;41(4):754–62.Google Scholar
Luurtsema, G, Schuit, RC, Klok, RP, et al. Evaluation of C-11 laniquidar as a tracer of P-glycoprotein: radiosynthesis and biodistribution in rats. Nucl Med Biol. 2009;36(6):643–9.Google Scholar
Syvänen, S, Luurtsema, G, Molthoff, C, et al. (R)-[11C]Verapamil PET studies to assess changes in P-glycoprotein expression and functionality in rat blood-brain barrier after exposure to kainate-induced status epilepticus. BMC Med Imaging. 2011;11(1):1.Google Scholar
Bankstahl, JP, Löscher, W. Resistance to antiepileptic drugs and expression of P-glycoprotein in two rat models of status epilepticus. Epilepsy Res. 2008;82(1):70–85.Google Scholar
Bartmann, H, Fuest, C, la Fougère, C, et al. Imaging of P-glycoprotein-mediated pharmacoresistance in the hippocampus: Proof-of-concept in a chronic rat model of temporal lobe epilepsy. Epilepsia. 2010;51(9):1780–90.Google Scholar
Syvänen, S, Russmann, V, Verbeek, J, et al. C-11 quinidine and C-11 laniquidar PET imaging in a chronic rodent epilepsy model: Impact of epilepsy and drug-responsiveness. Nucl Med Biol. 2013;40(6):764–75.Google Scholar
Müllauer, J, Karch, R, Bankstahl, JP, et al. Assessment of cerebral P-glycoprotein expression and function with PET by combined [C-11]inhibitor and [C-11]substrate scans in rats. Nucl Med Biol. 2013;40(6):755–63.Google Scholar
Yakushev, IY, Dupont, E, Buchholz, H-G, et al. In vivo imaging of dopamine receptors in a model of temporal lobe epilepsy. Epilepsia. 2010;51(3):415–22.Google Scholar
Goffin, K, Van Paesschen, W, Dupont, P, Van Laere, K. Longitudinal microPET imaging of brain glucose metabolism in rat lithium-pilocarpine model of epilepsy. Exp Neurol. 2009;217(1):205–9.Google Scholar
Guo, Y, Gao, F, Wang, S, et al. In vivo mapping of temporospatial changes in glucose utilization in rat brain during epileptogenesis: an [18F]-fluordeoxyglucose-small animal positron emission tomography study. Neuroscience. 2009;162(4):972–9.Google Scholar
Amhaoul, H, Hamaide, J, Bertoglio, D, et al. Brain inflammation in a chronic epilepsy model: Evolving pattern of the translocator protein during epileptogenesis. Neurobiol Dis. 2015;82:526–39.Google Scholar
Bogdanovic, RM, Syvänen, S, Michler, C, et al. (R)-C-11 PK11195 brain uptake as a biomarker of inflammation and antiepileptic drug resistance: evaluation in a rat epilepsy model. Neuropharmacology. 2014;85:104–12.Google Scholar
Maziere, M, Hantraye, P, Prenant, C, Sastre, J, Comar, D. Synthesis of ethyl 8-fluoro-5,6-dihydro-5-C11 methyl-6-oxo-4h-imidazo 1,5-a 1,4 benzodiazepine-3-carboxylate (RO 15.1788-11C)—a specific radioligand for the in vivo study of central benzodiazepine receptors by positron emission tomography. Int J Appl Radiat Isot. 1984;35(10):973–6.Google Scholar
Froklage, F, Syvanen, S, Hendrikse, NH, et al. [11C]Flumazenil brain uptake is influenced by the blood-brain barrier efflux transporter P-glycoprotein. EJNMMI Res. 2012;2(1):12.Google Scholar
Liefaard, LC, Ploeger, BA, Molthoff, CFM, et al. Changes in GABA(A) receptor properties in amygdala kindled animals: In vivo studies using [C-11]flumazenil and positron emission tomography. Epilepsia. 2009;50(1):88–98.Google Scholar
Syvänen, S, Labots, M, Tagawa, Y, et al. Altered GABAA receptor density and unaltered blood-brain barrier transport in a kainate model of epilepsy: an in vivo study using 11C-flumazenil and PET. J Nucl Med. 2012;53(12):1974–83.Google Scholar

References

Kwan, P, Brodie, MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342:314–9.Google Scholar
Kwan, P, Arzimanoglou, A, Berg, A, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc task force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51:1069–77.Google Scholar
Fisher, RS, Vickrey, BG, Gibson, P, et al. The impact of epilepsy from the patient’s perspective I. Descriptions and subjective perceptions. Epilepsy Res. 2000;41:39–51.Google Scholar
Bootsma, HP, Ricker, L, Hekster, YA, et al. The impact of side effects on long-term retention in three new antiepileptic drugs. Seizure. 2009;18:327–31.Google Scholar
Campos, BAG, Yasuda, CL, Castellano, G, Bilevicius, E, Li, LM, Cendes, F. Proton MRS may predict AED response in patients with TLE. Epilepsia. 2010;51:783–8.Google Scholar
Bilevicius, E, Yasuda, CL, Silva, MS, Guerreiro CAM, Lopes-Cendes I, Cendes F. Antiepileptic drug response in temporal lobe epilepsy: a clinical and MRI morphometry study. Neurology. 2010;75:1695–701.Google Scholar
Cardoso, TAM, Coan, AC, Kobayashi, E, Guerreiro CAM, Li LM, , Cendes, F. Hippocampal abnormalities and seizure recurrence after antiepileptic drug withdrawal. Neurology. 2006;67:134–6.Google Scholar
Stretton, J, Winston, G, Sidhu, M, et al. Neural correlates of working memory in temporal lobe epilepsy—an fMRI study. NeuroImage. 2012;60:1696–703.Google Scholar
Centeno, M, Vollmar, C, O’Muircheartaigh, J, et al. Memory in frontal lobe epilepsy: an fMRI study. Epilepsia. 2012;53:1756–64.Google Scholar
de Campos, BM, Coan, AC, Lin Yasuda, C, Casseb, RF, Cendes, F. Large-scale brain networks are distinctly affected in right and left mesial temporal lobe epilepsy. Hum Brain Mapp. 2016;37(9):3137–52.Google Scholar
Vollmar, C, O’Muircheartaigh, J, Barker, GJ, et al. Motor system hyperconnectivity in juvenile myoclonic epilepsy: a cognitive functional magnetic resonance imaging study. Brain J Neurol. 2011;134:1710–9.Google Scholar
Stretton, J, Winston, GP, Sidhu, M, et al. Disrupted segregation of working memory networks in temporal lobe epilepsy. NeuroImage Clin. 2013;2:273–81.Google Scholar
Danielson, NB, Guo, JN, Blumenfeld, H. The default mode network and altered consciousness in epilepsy. Behav Neurol. 2011;24:55–65.Google Scholar
Andrews-Hanna, JR, Reidler, JS, Sepulcre, J, Poulin, R, Buckner, RL. Functional-anatomic fractionation of the brain’s default network. Neuron. 2010;65:550–62.Google Scholar
Koepp, MJ. Gender and drug effects on neuroimaging in epilepsy. Epilepsia. 2011;52(suppl 4):35–7.Google Scholar
Mehta, MA, O’Daly, OG. Pharmacological application of fMRI. Methods Mol Biol. 2011;711:551–65.Google Scholar
Beltramini, GC, Cendes, F, Yasuda, CL. The effects of antiepileptic drugs on cognitive functional magnetic resonance imaging. Quant Imaging Med Surg. 2015;5:238–46.Google Scholar
Borsook, D, Becerra, L, Hargreaves, R. A role for fMRI in optimizing CNS drug development. Nat Rev Drug Discov. 2006;5:411–24.Google Scholar
Nathan, PJ, Phan, KL, Harmer, CJ, Mehta, MA, Bullmore, ET. Increasing pharmacological knowledge about human neurological and psychiatric disorders through functional neuroimaging and its application in drug discovery. Curr Opin Pharmacol. 2014;14:54–61.Google Scholar
Jokeit, H, Okujava, M, Woermann, FG. Carbamazepine reduces memory induced activation of mesial temporal lobe structures: a pharmacological fMRI-study. BMC Neurol. 2001;1:6.Google Scholar
Haneef, Z, Levin, HS, Chiang, S. Brain graph topology changes associated with anti-epileptic drug use. Brain Connect. 2015;5:284–91.Google Scholar
Bernhardt, BC, Chen, Z, He, Y, Evans, AC, Bernasconi, N. Graph-theoretical analysis reveals disrupted small-world organization of cortical thickness correlation networks in temporal lobe epilepsy. Cereb Cortex. 2011;21:2147–57.Google Scholar
Li, X, Large, CH, Ricci, R, et al. Using interleaved transcranial magnetic stimulation/functional magnetic resonance imaging (fMRI) and dynamic causal modeling to understand the discrete circuit specific changes of medications: lamotrigine and valproic acid changes in motor or prefrontal effective connectivity. Psychiatry Res. 2011;194:141–8.Google Scholar
Vollmar, C, O’Muircheartaigh, J, Symms, MR, et al. Altered microstructural connectivity in juvenile myoclonic epilepsy: the missing link. Neurology. 2012;78:1555–9.Google Scholar
Yacubian, EM, Wolf, P. Praxis induction. Definition, relation to epilepsy syndromes, nosological and prognostic significance. A focused review. Seizure. 2014;23:247–51.Google Scholar
Wandschneider, B, Thompson, PJ, Vollmar, C, Koepp, MJ. Frontal lobe function and structure in juvenile myoclonic epilepsy: a comprehensive review of neuropsychological and imaging data. Epilepsia. 2012;53:2091–8.Google Scholar
Szaflarski, JP, Kay, B, Gotman, J, Privitera, MD, Holland, SK. The relationship between the localization of the generalized spike and wave discharge generators and the response to valproate. Epilepsia. 2013;54:471–80.Google Scholar
Helmstaedter, C, Witt, J-A. The effects of levetiracetam on cognition: a non-interventional surveillance study. Epilepsy Behav. 2008;13:642–9.Google Scholar
Helmstaedter, C, Witt, J-A. Cognitive outcome of antiepileptic treatment with levetiracetam versus carbamazepine monotherapy: a non-interventional surveillance trial. Epilepsy Behav. 2010;18:74–80.Google Scholar
Wandschneider, B, Stretton, J, Sidhu, M, et al. Levetiracetam reduces abnormal network activations in temporal lobe epilepsy. Neurology. 2014;83:1508–12.Google Scholar
Cousijn, H, Rijpkema, M, Qin, S, van Wingen, GA, Fernández, G. Phasic deactivation of the medial temporal lobe enables working memory processing under stress. NeuroImage. 2012;59:1161–7.Google Scholar
Bakker, A, Krauss, GL, Albert, MS, et al. Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment. Neuron. 2012;74:467–74.Google Scholar
Bakker, A, Albert, MS, Krauss, G, Speck, CL, Gallagher, M. Response of the medial temporal lobe network in amnestic mild cognitive impairment to therapeutic intervention assessed by fMRI and memory task performance. NeuroImage Clin. 2015;7:688–98.Google Scholar
Abou-Khalil, BW. Antiepileptic drugs. Continuum. 2016;22:132–56.Google Scholar
Mula, M. Topiramate and cognitive impairment: evidence and clinical implications. Ther Adv Drug Saf. 2012;3:279–89.Google Scholar
Schulze-Bonhage, A. The safety and long-term efficacy of zonisamide as adjunctive therapy for focal epilepsy. Expert Rev Neurother. 2015;15:857–65.Google Scholar
Martin, R, Kuzniecky, R, Ho, S, et al. Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults. Neurology. 1999;52:321–7.Google Scholar
Thompson, PJ, Baxendale, SA, Duncan, JS, Sander, JW. Effects of topiramate on cognitive function. J Neurol Neurosurg Psychiatry. 2000;69:636–41.Google Scholar
Meador, KJ, Loring, DW, Vahle, VJ, et al. Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers. Neurology. 2005;64:2108–14.Google Scholar
Bootsma, HPR, Ricker, L, Diepman, L, et al. Long-term effects of levetiracetam and topiramate in clinical practice: a head-to-head comparison. Seizure. 2008;17:19–26.Google Scholar
Mula, M, Trimble, MR. Antiepileptic drug-induced cognitive adverse effects: potential mechanisms and contributing factors. CNS Drugs. 2009;23:121–37.Google Scholar
Ojemann, LM, Ojemann, GA, Dodrill, CB, Crawford, CA, Holmes, MD, Dudley, DL. Language disturbances as side effects of topiramate and zonisamide therapy. Epilepsy Behav. 2001;2:579–84.Google Scholar
Jansen, JFA, Aldenkamp, AP, Marian Majoie, HJ, et al. Functional MRI reveals declined prefrontal cortex activation in patients with epilepsy on topiramate therapy. Epilepsy Behav. 2006;9:181–5.Google Scholar
Szaflarski, JP, Allendorfer, JB. Topiramate and its effect on fMRI of language in patients with right or left temporal lobe epilepsy. Epilepsy Behav. 2012;24:74–80.Google Scholar
De Ciantis, A, Muti, M, Piccolini, C, et al. A functional MRI study of language disturbances in subjects with migraine headache during treatment with topiramate. Neurol Sci. 2008;29(suppl 1):S141–3.Google Scholar
Yasuda, CL, Centeno, M, Vollmar, C, et al. The effect of topiramate on cognitive fMRI. Epilepsy Res. 2013;105:250–5.Google Scholar
Tang, Y, Xia, W, Yu, X, et al. Altered cerebral activity associated with topiramate and its withdrawal in patients with epilepsy with language impairment: an fMRI study using the verb generation task. Epilepsy Behav. 2016;59:98–104.Google Scholar
Raichle, ME, MacLeod, AM, Snyder, AZ, Powers, WJ, Gusnard, DA, Shulman, GL. A default mode of brain function. Proc Natl Acad Sci USA. 2001;98:676–82.Google Scholar
Seghier, ML, Price, CJ. Functional heterogeneity within the default network during semantic processing and speech production. Front Psychol. 2012;3:281.Google Scholar
Wandschneider, B, Burdett, J, Townsend, L, et al. Effect of topiramate and zonisamide on fMRI cognitive networks. Neurology. 2017;88(12):1165–71.Google Scholar
Dodrill, CB. Effects of sulthiame upon intellectual, neuropsychological, and social functioning abilities among adult epileptics: comparison with diphenylhydantoin. Epilepsia. 1975;16:617–25.Google Scholar
Bruhn, H, Kleinschmidt, A, Boecker, H, Merboldt, KD, Hänicke, W, Frahm, J. The effect of acetazolamide on regional cerebral blood oxygenation at rest and under stimulation as assessed by MRI. J Cereb Blood Flow Metab. 1994;14:742–8.Google Scholar
van Veenendaal, TM, IJff, DM, Aldenkamp, AP, et al. Metabolic and functional MR biomarkers of antiepileptic drug effectiveness: a review. Neurosci Biobehav Rev. 2015;59:92–9.Google Scholar
Löscher, W, Klitgaard, H, Twyman, R, Schmidt, D. New avenues for anti-epileptic drug discovery and development. Nat Rev Drug Discov. 2013;12:757–76.Google Scholar
Sisodiya, SM, Lin, WR, Harding, BN, Squier, MV, Thom, M. Drug resistance in epilepsy: expression of drug resistance proteins in common causes of refractory epilepsy. Brain. 2002;125:22–31.Google Scholar
Juliano, R, Ling, V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta. 1976;455:152–62.Google Scholar
Sisodiya, SM, Bates, SE. Treatment of drug resistance in epilepsy: one step at a time. Lancet Neurol. 2006;5:380–1.Google Scholar
Löscher, W, Langer, O. Imaging of P-glycoprotein function and expression to elucidate mechanisms of pharmacoresistance in epilepsy. Curr Top Med Chem. 2010;10:1785–91.Google Scholar
Bankstahl, J, Kuntner, C, Abrahim, A, et al. Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET. J Nucl Med. 2008;49:1328–35.Google Scholar
Wagner, C, Feurstein, T, Karch, R, et al. A pilot study to assess the efficacy of tariquidar to inhibit P-glycoprotein at the human blood-brain barrier with (R)[11C]verapamil and PET. J Nucl Med. 2009;50:1192.Google Scholar
Bankstahl, J, Bankstahl, M, Kuntner, C, et al. A novel positron emission tomography imaging protocol identifies seizure-induced regional overactivity of P-glycoprotein at the blood-brain barrier. J Neurosci. 2011;31:8803–11.Google Scholar
Bartels, AL, Kortekaas, R, Bart, J, et al. Blood-brain barrier P-glycoprotein function decreases in specific brain regions with aging: a possible role in progressive neurodegeneration. Neurobiol Aging. 2009;30:1818–24.Google Scholar
Brunner, M, Langer, O, Sunder-Plassmann, R, et al. Influence of functional haplotypes in the drug transporter gene ABCB1 on central nervous system drug distribution in humans. Clin Pharmacol Ther. 2005;78:182–90.Google Scholar
Bauer, M, Karch, R, Neumann, F, et al. Assessment of regional differences in tariquidar-induced P-glycoprotein modulation at the human blood-brain barrier. J Cereb Blood Flow Metab. 2010;30:510–5.Google Scholar
Eyal, S, Ke, B, Muzi, M, et al. Regional P-glycoprotein activity and inhibition at the human blood-brain barrier as imaged by positron emission tomography. Clin Pharmacol Ther. 2010;87:579–85.Google Scholar
Langer, O, Bauer, M, Hammers, A, et al. Pharmacoresistance in epilepsy: a pilot PET study with the P-glycoprotein substrate R-[(11)C]verapamil. Epilepsia. 2007;48:1774–84.Google Scholar
Feldmann, M, Asselin, M-C, Liu, J, et al. P-glycoprotein expression and function in patients with temporal lobe epilepsy: a case-control study. Lancet Neurol. 2013;12:777–85.Google Scholar
Bauer, M, Karch, R, Zeitlinger, M, et al. In vivo P-glycoprotein function before and after epilepsy surgery. Neurology. 2014;83:1326–31.Google Scholar
Jensen, S, DiPaolo, A, Lastella, M, et al. Pharmacogenetics of ABCB1 and brain kinetics of 99 m-Tc-MIBI in epilepsy patients. Epilepsia. 2006;47(suppl 3):88–9.Google Scholar
Basic, S, Hajnsek, S, Bozina, N, et al. The influence of C3435 T polymorphism of ABCB1 gene on penetration of phenobarbital across blood-brain barrier in patients with generalized epilepsy. Seizure Eur J Epilepsy. 2008;17:524–30.Google Scholar
Seneca, N, Zoghbi, SS, Liow, J-S, et al. Human brain imaging and radiation dosimetry of 11C-N-desmethyl-loperamide, a PET radiotracer to measure the function of P-glycoprotein. J Nucl Med. 2009;50:807–13.Google Scholar
Kreisl, W, Liow, J, Kimura, N, et al. P-glycoprotein function at the blood-brain barrier in humans can be quantified with the substrate radiotracer 11C-N-desmethyl-loperamide. J Nucl Med. 2010;51:559–66.Google Scholar
Luna-Tortós, C, Fedrowitz, M, Löscher, W. Several major antiepileptic drugs are substrates for human P-glycoprotein. Neuropharmacology. 2008;55:1364–75.Google Scholar
Baron, J, Roeda, D, Munari, C, Crouzel, C, Chodkiewicz, J, Comar, D. Brain regional pharmacokinetics of 11C-labeled diphenylhydantoin: positron emission tomography in humans. Neurology. 1983;33:580–5.Google Scholar
Hammers, A, Bouvard, S, Costes, N, et al. Impact of P-glycoprotein on the distribution of [18 F]-MPPF in pharmacoresistant temporal lobe epilepsia. Epilepsia. 2010;51:48.Google Scholar
Kannan, P, John, C, Zoghbi, SS, et al. Imaging the function of P-glycoprotein with radiotracers: pharmacokinetics and in vivo applications. Clin Pharmacol Ther. 2009;86:368–77.Google Scholar
Summers, MA, Moore, JL, McAuley, JW. Use of verapamil as a potential P-glycoprotein inhibitor in a patient with refractory epilepsy. Ann Pharmacother. 2004;38:1631–4.Google Scholar
Van Vliet, EA, Van Schaik, R, Edelbroek, PM, et al. Inhibition of the multidrug transporter p-glycoprotein improves seizure control in phenytoin-treated chronic epileptic rats. Epilepsia. 2006;47:672–80.Google Scholar
Huls, M, Russel, FGM, Masereeuw, R. The role of ATP binding cassette transporters in tissue defense and organ regeneration. J Pharmacol Exp Ther. 2009;328:3–9.Google Scholar
Potschka, H. Modulating P-glycoprotein regulation: future perspectives for pharmacoresistant epilepsies? Epilepsia. 2010;51:1333–47.Google Scholar
Potschka, H. Animal and human data: where are our concepts for drug-resistant epilepsy going? Epilepsia. 2013;54:29–32.Google Scholar

References

de Tisi, J, Bell, GS, Peacock, JL, et al. The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study. Lancet. 2011;378:1388–95.Google Scholar
Bonilha, L, Keller, SS. Quantitative MRI in refractory temporal lobe epilepsy: relationship with surgical outcomes. Quant Imaging Med Surg. 2015;5:204–24.Google Scholar
Bernasconi, A, Bernasconi, N, Bernhardt, BC, et al. Advances in MRI for “cryptogenic” epilepsies. Nat Rev Neurol. 2011;7:99–108.Google Scholar
Yasuda, CL, Cendes, F. Neuroimaging for the prediction of response to medical and surgical treatment in epilepsy. Expert Opin Med Diagn. 2012;6:295–308.Google Scholar
West, S, Nolan, SJ, Cotton, J, et al. Surgery for epilepsy. Cochrane Database Syst Rev. 2015;7:CD010541.Google Scholar
Keller, SS, Richardson, MP, Schoene-Bake, JC, et al. Thalamotemporal alteration and postoperative seizures in temporal lobe epilepsy. Ann Neurol. 2015;77:760–74.Google Scholar
Lin, JJ, Salamon, N, Dutton, RA, et al. Three-dimensional preoperative maps of hippocampal atrophy predict surgical outcomes in temporal lobe epilepsy. Neurology. 2005;65:1094–7.Google Scholar
Bernhardt, BC, Kim, H, Bernasconi, N. Patterns of subregional mesiotemporal disease progression in temporal lobe epilepsy. Neurology. 2013;81:1840–7.Google Scholar
Bernhardt, BC, Hong, SJ, Bernasconi, A, et al. Magnetic resonance imaging pattern learning in temporal lobe epilepsy: classification and prognostics. Ann Neurol. 2015;77:436–46.Google Scholar
Doucet, GE, He, X, Sperling, M, et al. Frontal gray matter abnormalities predict seizure outcome in refractory temporal lobe epilepsy patients. NeuroImage Clin. 2015;9:458–66.Google Scholar
Feis, DL, Schoene-Bake, JC, Elger, C, et al. Prediction of post-surgical seizure outcome in left mesial temporal lobe epilepsy. NeuroImage Clin. 2013;2:903–11.Google Scholar
Yasuda, CL, Valise, C, Saude, AV, et al. Dynamic changes in white and gray matter volume are associated with outcome of surgical treatment in temporal lobe epilepsy. NeuroImage. 2010;49:71–9.Google Scholar
Wang, ZI, Jones, SE, Jaisani, Z, et al. Voxel-based morphometric magnetic resonance imaging (MRI) postprocessing in MRI-negative epilepsies. Ann Neurol. 2015;77:1060–75.Google Scholar
Leach, JL, Miles, L, Henkel, DM, et al. Magnetic resonance imaging abnormalities in the resection region correlate with histopathological type, gliosis extent, and postoperative outcome in pediatric cortical dysplasia. J Neurosurg Pediatr. 2014;14:68–80.CrossRefGoogle ScholarPubMed
Bernhardt, BC, Bernasconi, N, Concha, L, et al. Cortical thickness analysis in temporal lobe epilepsy: reproducibility and relation to outcome. Neurology. 2010;74:1776–84.Google Scholar
Bernhardt, BC, Chen, Z, He, Y, et al. Graph-theoretical analysis reveals disrupted small-world organization of cortical thickness correlation networks in temporal lobe epilepsy. Cereb Cortex. 2011;21:2147–57.Google Scholar
Bernhardt, BC, Bernasconi, N, Hong, SJ, et al. Subregional mesiotemporal network topology is altered in temporal lobe epilepsy. Cereb Cortex. 2016;26:3237–48.Google Scholar
Beaulieu, C. The basis of anisotropic water diffusion in the nervous system—a technical review. NMR Biomed. 2002;15:435–55.Google Scholar
Gross, DW. Diffusion tensor imaging in temporal lobe epilepsy. Epilepsia. 2011;52(suppl 4):32–4.Google Scholar
Goncalves Pereira, PM, Oliveira, E, Rosado, P. Apparent diffusion coefficient mapping of the hippocampus and the amygdala in pharmaco-resistant temporal lobe epilepsy. AJNR Am J Neuroradiol. 2006;27:671–83.Google Scholar
Bernhardt, BC, Bonilha, L, Gross, DW. Network analysis for a network disorder: the emerging role of graph theory in the study of epilepsy. Epilepsy Behav. 2015;50:162–70.Google Scholar
Bonilha, L, Helpern, JA, Sainju, R, et al. Presurgical connectome and postsurgical seizure control in temporal lobe epilepsy. Neurology. 2013;81:1704–10.Google Scholar
Bonilha, L, Jensen, JH, Baker, N, et al. The brain connectome as a personalized biomarker of seizure outcomes after temporal lobectomy. Neurology. 2015;84:1846–53.Google Scholar
Munsell, BC, Wee, CY, Keller, SS, et al. Evaluation of machine learning algorithms for treatment outcome prediction in patients with epilepsy based on structural connectome data. NeuroImage. 2015;118:219–30.Google Scholar
Hutchings, F, Han, CE, Keller, SS, et al. Predicting surgery targets in temporal lobe epilepsy through structural connectome based simulations. PLOS Comput Biol. 2015;11:e1004642.Google Scholar
Cendes, F, Knowlton Robert, C, Novotny, E, et al. Magnetic resonance spectroscopy in epilepsy: clinical issues. Epilepsia. 2002;43:32–9.Google Scholar
Duncan, JS. Imaging in the surgical treatment of epilepsy. Nat Rev Neurol. 2010;6:537–50.Google Scholar
Struck, AF, Hall, LT, Floberg, JM, et al. Surgical decision making in temporal lobe epilepsy: a comparison of [(18)F]FDG-PET, MRI, and EEG. Epilepsy Behav. 2011;22:293–7.Google Scholar
Burneo, JG, Poon, R, Kellett, S, et al. The utility of positron emission tomography in epilepsy. Can J Neurol Sci. 2015;42:360–71.Google Scholar
Wehner, T, Lüders, H. Role of neuroimaging in the presurgical evaluation of epilepsy. J Clin Neurol. 2008;4:1–16.Google Scholar
LoPinto-Khoury, C, Sperling, MR, Skidmore, C, et al. Surgical outcome in PET-positive, MRI-negative patients with temporal lobe epilepsy. Epilepsia. 2012;53:342–8.Google Scholar
Yankam Njiwa, J, Gray, KR, Costes, N, et al. Advanced [(18)F]FDG and [(11)C]flumazenil PET analysis for individual outcome prediction after temporal lobe epilepsy surgery for hippocampal sclerosis. NeuroImage Clin. 2015;7:122–31.Google Scholar
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.Google Scholar
Dupont, S, Semah, F, Clemenceau, S, et al. Accurate prediction of postoperative outcome in mesial temporal lobe epilepsy: a study using positron emission tomography with 18fluorodeoxyglucose. Arch Neurol. 2000;57:1331–6.Google Scholar
Wong, CH, Bleasel, A, Wen, L, et al. The topography and significance of extratemporal hypometabolism in refractory mesial temporal lobe epilepsy examined by FDG-PET. Epilepsia. 2010;51:1365–73.Google Scholar
Vinton, AB, Carne, R, Hicks, RJ, et al. The extent of resection of FDG-PET hypometabolism relates to outcome of temporal lobectomy. Brain. 2007;130:548–60.Google Scholar
Carne, RP, O’Brien, TJ, Kilpatrick, CJ, et al. MRI-negative PET-positive temporal lobe epilepsy: a distinct surgically remediable syndrome. Brain. 2004;127:2276–85.Google Scholar
Chandra, PS, Salamon, N, Huang, J, et al. FDG-PET/MRI coregistration and diffusion-tensor imaging distinguish epileptogenic tubers and cortex in patients with tuberous sclerosis complex: a preliminary report. Epilepsia. 2006;47:1543–9.Google Scholar
Yun, CH, Lee, SK, Lee, SY, et al. Prognostic factors in neocortical epilepsy surgery: multivariate analysis. Epilepsia. 2006;47:574–9.Google Scholar
Chassoux, F, Rodrigo, S, Semah, F, et al. FDG-PET improves surgical outcome in negative MRI Taylor-type focal cortical dysplasias. Neurology. 2010;75:2168–75.Google Scholar
Knowlton, RC, Elgavish, RA, Bartolucci, A, et al. Functional imaging: II. Prediction of epilepsy surgery outcome. Ann Neurol. 2008;64:35–41.Google Scholar
Lee, SK, Lee, SY, Kim, KK, et al. Surgical outcome and prognostic factors of cryptogenic neocortical epilepsy. Ann Neurol. 2005;58:525–32.Google Scholar
Koepp, MJ, Woermann, FG. Imaging structure and function in refractory focal epilepsy. Lancet Neurol. 2005;4:42–53.Google Scholar
Juhasz, C, Asano, E, Shah, A, et al. Focal decreases of cortical GABAA receptor binding remote from the primary seizure focus: what do they indicate? Epilepsia. 2009;50:240–50.Google Scholar
Chugani, HT, Luat, AF, Kumar, A, et al. alpha-[11C]-methyl-L-tryptophan–PET in 191 patients with tuberous sclerosis complex. Neurology. 2013;81:674–80.Google Scholar
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.Google Scholar
Dupont, P, Van Paesschen, W, Palmini, A, et al. Ictal perfusion patterns associated with single MRI-visible focal dysplastic lesions: implications for the noninvasive delineation of the epileptogenic zone. Epilepsia. 2006;47:1550–7.Google Scholar
O’Brien, TJ, So, EL, Cascino, GD, et al. Subtraction SPECT coregistered to MRI in focal malformations of cortical development: localization of the epileptogenic zone in epilepsy surgery candidates. Epilepsia. 2004;45:367–76.Google Scholar
Tepmongkol, S, Tangtrairattanakul, K, Lerdlum, S, et al. Comparison of brain perfusion SPECT parameters accuracy for seizure localization in extratemporal lobe epilepsy with discordant pre-surgical data. Ann Nucl Med. 2015;29:21–8.Google Scholar
Krsek, P, Kudr, M, Jahodova, A, et al. Localizing value of ictal SPECT is comparable to MRI and EEG in children with focal cortical dysplasia. Epilepsia. 2013;54:351–8.Google Scholar
Kazemi, NJ, Worrell, GA, Stead, SM, et al. Ictal SPECT statistical parametric mapping in temporal lobe epilepsy surgery. Neurology. 2010;74:70–6.Google Scholar
McNally, KA, Paige, AL, Varghese, G, et al. Localizing value of ictal-interictal SPECT analyzed by SPM (ISAS). Epilepsia. 2005;46:1450–64.Google Scholar
Sulc, V, Stykel, S, Hanson, DP, et al. Statistical SPECT processing in MRI-negative epilepsy surgery. Neurology. 2014;82:932–9.Google Scholar
Ogawa, S, Tank, DW, Menon, R, et al. Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. Proc Natl Acad Sci USA. 1992;89:5951–5.Google Scholar
Biswal, BB. Resting state fMRI: a personal history. NeuroImage. 2012;62:938–44.Google Scholar
Zhang, CH, Lu, Y, Brinkmann, B, et al. Lateralization and localization of epilepsy related hemodynamic foci using presurgical fMRI. Clin Neurophysiol. 2015;126:27–38.Google Scholar
Negishi, M, Martuzzi, R, Novotny, EJ, et al. Functional MRI connectivity as a predictor of the surgical outcome of epilepsy. Epilepsia. 2011;52:1733–40.Google Scholar
Bagshaw, AP, Kobayashi, E, Dubeau, F, et al. Correspondence between EEG-fMRI and EEG dipole localisation of interictal discharges in focal epilepsy. NeuroImage. 2006;30:417–25.Google Scholar
Kobayashi, E, Hawco, CS, Grova, C, et al. Widespread and intense BOLD changes during brief focal electrographic seizures. Neurology. 2006;66:1049–55.Google Scholar
Thornton, R, Laufs, H, Rodionov, R, et al. EEG correlated functional MRI and postoperative outcome in focal epilepsy. J Neurol Neurosurg Psychiatry. 2010;81:922–7.Google Scholar
Morgan, VL, Sonmezturk, HH, Gore, JC, et al. Lateralization of temporal lobe epilepsy using resting functional magnetic resonance imaging connectivity of hippocampal networks. Epilepsia. 2012;53:1628–35.Google Scholar
Coan, AC, Chaudhary, UJ, Grouiller, F, et al. EEG-fMRI in the presurgical evaluation of temporal lobe epilepsy. J Neurol Neurosurg Psychiatry. 2016;87:642–9.Google Scholar
Elshoff, L, Groening, K, Grouiller, F, et al. The value of EEG-fMRI and EEG source analysis in the presurgical setup of children with refractory focal epilepsy. Epilepsia. 2012;53:1597–606.Google Scholar
An, D, Fahoum, F, Hall, J, et al. Electroencephalography/functional magnetic resonance imaging responses help predict surgical outcome in focal epilepsy. Epilepsia. 2013;54:2184–94.Google Scholar
Michel, CM, Lantz, G, Spinelli, L, et al. 128-channel EEG source imaging in epilepsy: clinical yield and localization precision. J Clin Neurophysiol. 2004;21:71–83.Google Scholar
Plummer, C, Harvey, AS, Cook, M. EEG source localization in focal epilepsy: where are we now? Epilepsia. 2008;49:201–18.Google Scholar
Zumsteg, D, Friedman, A, Wieser, HG, et al. Propagation of interictal discharges in temporal lobe epilepsy: correlation of spatiotemporal mapping with intracranial foramen ovale electrode recordings. Clin Neurophysiol. 2006;117:2615–26.Google Scholar
Gavaret, M, Badier, JM, Marquis, P, et al. Electric source imaging in temporal lobe epilepsy. J Clin Neurophysiol. 2004;21:267–82.Google Scholar
Gavaret, M, Badier, JM, Marquis, P, et al. Electric source imaging in frontal lobe epilepsy. J Clin Neurophysiol. 2006;23:358–70.Google Scholar
Feng, R, Hu, J, Pan, L, et al. Application of 256-channel dense array electroencephalographic source imaging in presurgical workup of temporal lobe epilepsy. Clin Neurophysiol. 2016;127:108–16.Google Scholar
Megevand, P, Spinelli, L, Genetti, M, et al. Electric source imaging of interictal activity accurately localises the seizure onset zone. J Neurol Neurosurg Psychiatry. 2014;85:38–43.Google Scholar
Russo, A, Jayakar, P, Lallas, M, et al. The diagnostic utility of 3D electroencephalography source imaging in pediatric epilepsy surgery. Epilepsia. 2016;57:24–31.Google Scholar
Brodbeck, V, Spinelli, L, Lascano, AM, et al. Electroencephalographic source imaging: a prospective study of 152 operated epileptic patients. Brain. 2011;134:2887–97.Google Scholar
Lascano, AM, Perneger, T, Vulliemoz, S, et al. Yield of MRI, high-density electric source imaging (HD-ESI), SPECT and PET in epilepsy surgery candidates. Clin Neurophysiol. 2016;127:150–5.Google Scholar
Heers, M, Hedrich, T, An, D, et al. Spatial correlation of hemodynamic changes related to interictal epileptic discharges with electric and magnetic source imaging. Hum Brain Mapp. 2014;35:4396–414.Google Scholar
Tanaka, N, Peters, JM, Prohl, AK, et al. Clinical value of magnetoencephalographic spike propagation represented by spatiotemporal source analysis: correlation with surgical outcome. Epilepsy Res. 2014;108:280–8.Google Scholar
Knowlton, RC. Can magnetoencephalography aid epilepsy surgery? Epilepsy Curr. 2008;8:1–5.Google Scholar
Eliashiv, DS, Elsas, SM, Squires, K, et al. Ictal magnetic source imaging as a localizing tool in partial epilepsy. Neurology. 2002;59:1600–10.Google Scholar
Knowlton, RC. The role of FDG-PET, ictal SPECT, and MEG in the epilepsy surgery evaluation. Epilepsy Behav. 2006;8:91–101.Google Scholar
Oishi, M, Kameyama, S, Masuda, H, et al. Single and multiple clusters of magnetoencephalographic dipoles in neocortical epilepsy: significance in characterizing the epileptogenic zone. Epilepsia. 2006;47:355–64.Google Scholar
Wheless, JW, Willmore, LJ, Breier, JI, et al. A comparison of magnetoencephalography, MRI, and V-EEG in patients evaluated for epilepsy surgery. Epilepsia. 1999;40:931–41.Google Scholar
Iwasaki, M, Nakasato, N, Shamoto, H, et al. Surgical implications of neuromagnetic spike localization in temporal lobe epilepsy. Epilepsia. 2002;43:415–24.Google Scholar
Stefan, H, Hummel, C, Scheler, G, et al. Magnetic brain source imaging of focal epileptic activity: a synopsis of 455 cases. Brain. 2003;126:2396–405.Google Scholar
Genow, A, Hummel, C, Scheler, G, et al. Epilepsy surgery, resection volume and MSI localization in lesional frontal lobe epilepsy. NeuroImage. 2004;21:444–9.Google Scholar

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