Advertisement

Nicotinic receptor abnormalities as a biomarker in idiopathic generalized epilepsy

  • Valentina GaribottoEmail author
  • Michael Wissmeyer
  • Zoi Giavri
  • Rachel Goldstein
  • Yann Seimbille
  • Margitta Seeck
  • Osman Ratib
  • Sven Haller
  • Fabienne PicardEmail author
Original Article
  • 172 Downloads

Abstract

Purpose

Mutations of cholinergic neuronal nicotinic receptors have been identified in the autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), associated with changes on PET images using [18F]-F-85380-A (F-A-85380), an α4β2 nicotinic receptor ligand. The aim of the present study was to evaluate potential changes in nicotinic receptor availability in other types of epilepsy.

Methods

We included 34 male participants, 12 patients with idiopathic generalized epilepsy (IGE), 10 with non-lesional diurnal focal epilepsy, and 12 age-matched healthy controls. All patients underwent PET/CT using F-A-85380 and [18F]-fluorodeoxyglucose (FDG), 3D T1 MRI and diffusion tensor imaging (DTI). F-A-85380 and FDG images were compared with the control group using a voxel-wise (SPM12) and a volumes of interest (VOI) analysis.

Results

In the group of patients with IGE, the voxel-wise and VOI analyses showed a significant increase of F-A-85380 ratio index of binding potential (BPRI, corresponding to the receptor availability) in the anterior cingulate cortex (ACC), without structural changes on MRI. At an individual level, F-A-85380 BPRI increase in the ACC could distinguish IGE patients from controls and from patients with focal epilepsy with good accuracy.

Conclusions

We observed focal changes of density/availability of nicotinic receptors in IGE, namely an increase in the ACC. These data suggest that the modulation of α4β2 nicotinic receptors plays a role not only in ADNFLE, but also in other genetic epileptic syndromes such as IGE and could serve as a biomarker of epilepsy syndromes with a genetic background.

Keywords

Nicotinic receptors Focal epilepsy Idiopathic generalized epilepsy PET F-A-85380 

Notes

Acknowledgements

We would like to thank Antoine Depaulis (Grenoble Institut des Neurosciences, France), Michel Bottlaender (CEA, NeuroSpin, Gif / Yvette, France) and Frédéric Bois (Geneva University Hospitals, Geneva, Switzerland) for helpful comments, Claire Bridel (University Hospitals of Geneva) for her help in the recruitment of the individuals, and Marie-Louise Montandon for her work in MRI analyses. With contributions of the Clinical Research Center, Geneva University Hospitals and Faculty of Medicine, Geneva.

Author contributions

FP, MW, MS, OR, YS, VG and SH contributed to the conception and design of the study, VG, SH, GZ, RG, YS, FP and MW performed acquisition and analysis of data, FP, VG, MS, OR and SH drafted the manuscript.

Funding

The work was funded by the Swiss National Science Foundation (n° 320030_127608).

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study involving human participants were conducted in accordance with the Swiss ethical standards and with the 1964 Helsinki declaration and its later amendments. The study protocol was approved by the Ethics Committee of the Geneva University Hospitals (CER 10-041) and by the Swiss agency for medications (Swissmedic: study n°2011DR1031). The study was recorded in ClinicalTrials.gov (n° NCT03268369).

Written informed consent was obtained from all participants.

References

  1. 1.
    Picard F, Scheffer I. Genetically determined focal epilepsies. In: Bureau M, Genton P, Dravet C, Delgado-Escueta AV, Tassinari CA, Thomas P, et al., editors. Epileptic syndromes in infancy, childhood and adolescence. 5th ed. Montrouge: John Libbey Eurotext; 2012. p. 349–61.Google Scholar
  2. 2.
    Dineley KT, Pandya AA, Yakel JL. Nicotinic ACh receptors as therapeutic targets in CNS disorders. Trends Pharmacol Sci. 2015;36(2):96–108.  https://doi.org/10.1016/j.tips.2014.12.002.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Walsh RM Jr, Roh SH, Gharpure A, Morales-Perez CL, Teng J, Hibbs RE. Structural principles of distinct assemblies of the human alpha4beta2 nicotinic receptor. Nature. 2018;557(7704):261–5.  https://doi.org/10.1038/s41586-018-0081-7.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Sadaghiani S, Ng B, Altmann A, Poline JB, Banaschewski T, Bokde ALW, et al. Overdominant effect of a CHRNA4 polymorphism on cingulo-opercular network activity and cognitive control. J Neurosci. 2017;37(40):9657–66.  https://doi.org/10.1523/JNEUROSCI.0991-17.2017.CrossRefPubMedGoogle Scholar
  5. 5.
    Valentine G, Sofuoglu M. Cognitive effects of nicotine: recent progress. Curr Neuropharmacol. 2018;16(4):403–14.  https://doi.org/10.2174/1570159X15666171103152136.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Dani JA. Overview of nicotinic receptors and their roles in the central nervous system. Biol Psychiatry. 2001;49(3):166–74.CrossRefGoogle Scholar
  7. 7.
    Picard F, Bruel D, Servent D, Saba W, Fruchart-Gaillard C, Schollhorn-Peyronneau MA, et al. Alteration of the in vivo nicotinic receptor density in ADNFLE patients: a PET study. Brain. 2006;129(Pt 8):2047–60.  https://doi.org/10.1093/brain/awl156.CrossRefPubMedGoogle Scholar
  8. 8.
    Rozycka A, Steinborn B, Trzeciak WH. The 1674+11C>T polymorphism of CHRNA4 is associated with juvenile myoclonic epilepsy. Seizure. 2009;18(8):601–3.  https://doi.org/10.1016/j.seizure.2009.06.007.CrossRefPubMedGoogle Scholar
  9. 9.
    Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, 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.  https://doi.org/10.1111/j.1528-1167.2010.02522.x.CrossRefGoogle Scholar
  10. 10.
    Ashburner J, Friston KJ. Voxel-based morphometry--the methods. NeuroImage. 2000;11(6 Pt 1):805–21.  https://doi.org/10.1006/nimg.2000.0582.CrossRefPubMedGoogle Scholar
  11. 11.
    Smith SM, Johansen-Berg H, Jenkinson M, Rueckert D, Nichols TE, Miller KL, et al. Acquisition and voxelwise analysis of multi-subject diffusion data with tract-based spatial statistics. Nat Protoc. 2007;2(3):499–503.  https://doi.org/10.1038/nprot.2007.45.CrossRefPubMedGoogle Scholar
  12. 12.
    Smith SM, Nichols TE. Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. NeuroImage. 2009;44(1):83–98.  https://doi.org/10.1016/j.neuroimage.2008.03.061.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Gallezot JD, Bottlaender M, Gregoire MC, Roumenov D, Deverre JR, Coulon C, et al. In vivo imaging of human cerebral nicotinic acetylcholine receptors with 2-18F-fluoro-A-85380 and PET. J Nucl Med. 2005;46(2):240–7.PubMedGoogle Scholar
  14. 14.
    Okada H, Ouchi Y, Ogawa M, Futatsubashi M, Saito Y, Yoshikawa E, et al. Alterations in alpha4beta2 nicotinic receptors in cognitive decline in Alzheimer’s aetiopathology. Brain. 2013;136(Pt 10):3004–17.  https://doi.org/10.1093/brain/awt195.CrossRefPubMedGoogle Scholar
  15. 15.
    Sabri O, Kendziorra K, Wolf H, Gertz HJ, Brust P. Acetylcholine receptors in dementia and mild cognitive impairment. Eur J Nucl Med Mol Imaging. 2008;35(Suppl 1):S30–45.  https://doi.org/10.1007/s00259-007-0701-1.CrossRefPubMedGoogle Scholar
  16. 16.
    Meyer PM, Strecker K, Kendziorra K, Becker G, Hesse S, Woelpl D, et al. Reduced alpha4beta2*-nicotinic acetylcholine receptor binding and its relationship to mild cognitive and depressive symptoms in Parkinson disease. Arch Gen Psychiatry. 2009;66(8):866–77.  https://doi.org/10.1001/archgenpsychiatry.2009.106.CrossRefPubMedGoogle Scholar
  17. 17.
    Kendziorra K, Wolf H, Meyer PM, Barthel H, Hesse S, Becker GA, et al. Decreased cerebral alpha4beta2* nicotinic acetylcholine receptor availability in patients with mild cognitive impairment and Alzheimer’s disease assessed with positron emission tomography. Eur J Nucl Med Mol Imaging. 2011;38(3):515–25.  https://doi.org/10.1007/s00259-010-1644-5.CrossRefPubMedGoogle Scholar
  18. 18.
    Nichols TE, Holmes AP. Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum Brain Mapp. 2002;15(1):1–25.  https://doi.org/10.1002/hbm.1058.CrossRefPubMedGoogle Scholar
  19. 19.
    Maldjian JA, Laurienti PJ, Kraft RA, Burdette JH. An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. NeuroImage. 2003;19(3):1233–9.CrossRefGoogle Scholar
  20. 20.
    Picard F, Sadaghiani S, Leroy C, Courvoisier DS, Maroy R, Bottlaender M. High density of nicotinic receptors in the cingulo-insular network. NeuroImage. 2013;79:42–51.  https://doi.org/10.1016/j.neuroimage.2013.04.074.CrossRefPubMedGoogle Scholar
  21. 21.
    Seneviratne U, Cook M, D’Souza W. Focal abnormalities in idiopathic generalized epilepsy: a critical review of the literature. Epilepsia. 2014;55(8):1157–69.  https://doi.org/10.1111/epi.12688.CrossRefPubMedGoogle Scholar
  22. 22.
    Depaulis A, David O, Charpier S. The genetic absence epilepsy rat from Strasbourg as a model to decipher the neuronal and network mechanisms of generalized idiopathic epilepsies. J Neurosci Methods. 2016;260:159–74.  https://doi.org/10.1016/j.jneumeth.2015.05.022.CrossRefPubMedGoogle Scholar
  23. 23.
    Luttjohann A, van Luijtelaar G. Dynamics of networks during absence seizure’s on- and offset in rodents and man. Front Physiol. 2015;6:16.  https://doi.org/10.3389/fphys.2015.00016.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Meeren HK, Pijn JP, Van Luijtelaar EL, Coenen AM, Lopes da Silva FH. Cortical focus drives widespread corticothalamic networks during spontaneous absence seizures in rats. J Neurosci. 2002;22(4):1480–95.CrossRefGoogle Scholar
  25. 25.
    Meeren H, van Luijtelaar G, Lopes da Silva F, Coenen A. Evolving concepts on the pathophysiology of absence seizures: the cortical focus theory. Arch Neurol. 2005;62(3):371–6.  https://doi.org/10.1001/archneur.62.3.371.CrossRefPubMedGoogle Scholar
  26. 26.
    Pinault D. Cellular interactions in the rat somatosensory thalamocortical system during normal and epileptic 5-9 Hz oscillations. J Physiol. 2003;552(Pt 3):881–905.  https://doi.org/10.1113/jphysiol.2003.046573.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Polack PO, Guillemain I, Hu E, Deransart C, Depaulis A, Charpier S. Deep layer somatosensory cortical neurons initiate spike-and-wave discharges in a genetic model of absence seizures. J Neurosci. 2007;27(24):6590–9.  https://doi.org/10.1523/JNEUROSCI.0753-07.2007.CrossRefPubMedGoogle Scholar
  28. 28.
    David O, Guillemain I, Saillet S, Reyt S, Deransart C, Segebarth C, et al. Identifying neural drivers with functional MRI: an electrophysiological validation. PLoS Biol. 2008;6(12):2683–97.  https://doi.org/10.1371/journal.pbio.0060315.CrossRefPubMedGoogle Scholar
  29. 29.
    Holmes MD, Brown M, Tucker DM. Are "generalized" seizures truly generalized? Evidence of localized mesial frontal and frontopolar discharges in absence. Epilepsia. 2004;45(12):1568–79.  https://doi.org/10.1111/j.0013-9580.2004.23204.x.CrossRefPubMedGoogle Scholar
  30. 30.
    Holmes MD, Quiring J, Tucker DM. Evidence that juvenile myoclonic epilepsy is a disorder of frontotemporal corticothalamic networks. NeuroImage. 2010;49(1):80–93.  https://doi.org/10.1016/j.neuroimage.2009.08.004.CrossRefPubMedGoogle Scholar
  31. 31.
    Zhang Z, Liao W, Chen H, Mantini D, Ding JR, Xu Q, et al. Altered functional-structural coupling of large-scale brain networks in idiopathic generalized epilepsy. Brain. 2011;134(Pt 10):2912–28.  https://doi.org/10.1093/brain/awr223.CrossRefPubMedGoogle Scholar
  32. 32.
    Westmijse I, Ossenblok P, Gunning B, van Luijtelaar G. Onset and propagation of spike and slow wave discharges in human absence epilepsy: a MEG study. Epilepsia. 2009;50(12):2538–48.  https://doi.org/10.1111/j.1528-1167.2009.02162.x.CrossRefPubMedGoogle Scholar
  33. 33.
    Bai X, Vestal M, Berman R, Negishi M, Spann M, Vega C, et al. Dynamic time course of typical childhood absence seizures: EEG, behavior, and functional magnetic resonance imaging. J Neurosci. 2010;30(17):5884–93.  https://doi.org/10.1523/JNEUROSCI.5101-09.2010.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    O’Muircheartaigh J, Vollmar C, Barker GJ, Kumari V, Symms MR, Thompson P, et al. Focal structural changes and cognitive dysfunction in juvenile myoclonic epilepsy. Neurology. 2011;76(1):34–40.  https://doi.org/10.1212/WNL.0b013e318203e93d.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Braga AM, Fujisao EK, Verdade RC, Paschoalato RP, Yamashita S, Betting LE. Investigation of the cingulate cortex in idiopathic generalized epilepsy. Epilepsia. 2015;56(11):1803–11.  https://doi.org/10.1111/epi.13205.CrossRefPubMedGoogle Scholar
  36. 36.
    Woermann FG, Free SL, Koepp MJ, Sisodiya SM, Duncan JS. Abnormal cerebral structure in juvenile myoclonic epilepsy demonstrated with voxel-based analysis of MRI. Brain. 1999;122(Pt 11):2101–8.CrossRefGoogle Scholar
  37. 37.
    Alhusaini S, Ronan L, Scanlon C, Whelan CD, Doherty CP, Delanty N, et al. Regional increase of cerebral cortex thickness in juvenile myoclonic epilepsy. Epilepsia. 2013;54(9):e138–41.  https://doi.org/10.1111/epi.12330.CrossRefPubMedGoogle Scholar
  38. 38.
    Cao B, Tang Y, Li J, Zhang X, Shang HF, Zhou D. A meta-analysis of voxel-based morphometry studies on gray matter volume alteration in juvenile myoclonic epilepsy. Epilepsy Res. 2013;106(3):370–7.  https://doi.org/10.1016/j.eplepsyres.2013.07.003.CrossRefPubMedGoogle Scholar
  39. 39.
    Paulus FM, Krach S, Blanke M, Roth C, Belke M, Sommer J, et al. Fronto-insula network activity explains emotional dysfunctions in juvenile myoclonic epilepsy: combined evidence from pupillometry and fMRI. Cortex. 2015;65:219–31.  https://doi.org/10.1016/j.cortex.2015.01.018.CrossRefPubMedGoogle Scholar
  40. 40.
    Vollmar C, O’Muircheartaigh J, Symms MR, Barker GJ, Thompson P, Kumari V, et al. Altered microstructural connectivity in juvenile myoclonic epilepsy: the missing link. Neurology. 2012;78(20):1555–9.  https://doi.org/10.1212/WNL.0b013e3182563b44.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Swartz BE, Simpkins F, Halgren E, Mandelkern M, Brown C, Krisdakumtorn T, et al. Visual working memory in primary generalized epilepsy: an 18FDG-PET study. Neurology. 1996;47(5):1203–12.CrossRefGoogle Scholar
  42. 42.
    Danober L, Depaulis A, Marescaux C, Vergnes M. Effects of cholinergic drugs on genetic absence seizures in rats. Eur J Pharmacol. 1993;234(2-3):263–8.CrossRefGoogle Scholar
  43. 43.
    Berdiev RK, Chepurnov SA, Veening JG, Chepurnova NE, van Luijtelaar G. The role of the nucleus basalis of Meynert and reticular thalamic nucleus in pathogenesis of genetically determined absence epilepsy in rats: a lesion study. Brain Res. 2007;1185:266–74.  https://doi.org/10.1016/j.brainres.2007.09.010.CrossRefPubMedGoogle Scholar
  44. 44.
    Danober L, Vergnes M, Depaulis A, Marescaux C. Nucleus basalis lesions suppress spike and wave discharges in rats with spontaneous absence-epilepsy. Neuroscience. 1994;59(3):531–9.CrossRefGoogle Scholar
  45. 45.
    Berdiev RK, van Luijtelaar G. Cholinergic stimulation of the nucleus basalis of Meynert and reticular thalamic nucleus affects spike-and-wave discharges in WAG/Rij rats. Neurosci Lett. 2009;463(3):249–53.  https://doi.org/10.1016/j.neulet.2009.07.068.CrossRefPubMedGoogle Scholar
  46. 46.
    Depaulis A, Charpier S. Pathophysiology of absence epilepsy: insights from genetic models. Neurosci Lett. 2017.  https://doi.org/10.1016/j.neulet.2017.02.035.
  47. 47.
    Kassam SM, Herman PM, Goodfellow NM, Alves NC, Lambe EK. Developmental excitation of corticothalamic neurons by nicotinic acetylcholine receptors. J Neurosci. 2008;28(35):8756–64.  https://doi.org/10.1523/JNEUROSCI.2645-08.2008.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Dickinson JA, Kew JN, Wonnacott S. Presynaptic alpha 7- and beta 2-containing nicotinic acetylcholine receptors modulate excitatory amino acid release from rat prefrontal cortex nerve terminals via distinct cellular mechanisms. Mol Pharmacol. 2008;74(2):348–59.  https://doi.org/10.1124/mol.108.046623.CrossRefPubMedGoogle Scholar
  49. 49.
    Alkondon M, Pereira EF, Eisenberg HM, Albuquerque EX. Nicotinic receptor activation in human cerebral cortical interneurons: a mechanism for inhibition and disinhibition of neuronal networks. J Neurosci. 2000;20(1):66–75.CrossRefGoogle Scholar
  50. 50.
    Liu JJ, Mohila CA, Gong Y, Govindarajan N, Onn SP. Chronic nicotine exposure during adolescence differentially influences calcium-binding proteins in rat anterior cingulate cortex. Eur J Neurosci. 2005;22(10):2462–74.  https://doi.org/10.1111/j.1460-9568.2005.04423.x.CrossRefPubMedGoogle Scholar
  51. 51.
    Mansvelder HD, Mertz M, Role LW. Nicotinic modulation of synaptic transmission and plasticity in cortico-limbic circuits. Semin Cell Dev Biol. 2009;20(4):432–40.  https://doi.org/10.1016/j.semcdb.2009.01.007.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Couey JJ, Meredith RM, Spijker S, Poorthuis RB, Smit AB, Brussaard AB, et al. Distributed network actions by nicotine increase the threshold for spike-timing-dependent plasticity in prefrontal cortex. Neuron. 2007;54(1):73–87.  https://doi.org/10.1016/j.neuron.2007.03.006.CrossRefPubMedGoogle Scholar
  53. 53.
    Bekenstein U, Mishra N, Milikovsky DZ, Hanin G, Zelig D, Sheintuch L, et al. Dynamic changes in murine forebrain miR-211 expression associate with cholinergic imbalances and epileptiform activity. Proc Natl Acad Sci U S A. 2017;114(25):E4996–5005.  https://doi.org/10.1073/pnas.1701201114.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Tang G, Gudsnuk K, Kuo SH, Cotrina ML, Rosoklija G, Sosunov A, et al. Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits. Neuron. 2014;83(5):1131–43.  https://doi.org/10.1016/j.neuron.2014.07.040.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Thomas MS, Davis R, Karmiloff-Smith A, Knowland VC, Charman T. The over-pruning hypothesis of autism. Dev Sci. 2016;19(2):284–305.  https://doi.org/10.1111/desc.12303.CrossRefPubMedGoogle Scholar
  56. 56.
    Pavlakis PP, Douglass LM. Pearls & Oysters: a case of refractory nocturnal seizures: putting out fires without smoke. Neurology. 2015;84(18):e134–6.  https://doi.org/10.1212/WNL.0000000000001539.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Brodtkorb E, Picard F. Tobacco habits modulate autosomal dominant nocturnal frontal lobe epilepsy. Epilepsy Behav. 2006;9(3):515–20.  https://doi.org/10.1016/j.yebeh.2006.07.008.CrossRefPubMedGoogle Scholar
  58. 58.
    Willoughby JO, Pope KJ, Eaton V. Nicotine as an antiepileptic agent in ADNFLE: an N-of-one study. Epilepsia. 2003;44(9):1238–40.CrossRefGoogle Scholar
  59. 59.
    Rathouz PJ, Zhao Q, Jones JE, Jackson DC, Hsu DA, Stafstrom CE, et al. Cognitive development in children with new onset epilepsy. Dev Med Child Neurol. 2014;56(7):635–41.  https://doi.org/10.1111/dmcn.12432.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Chowdhury FA, Elwes RD, Koutroumanidis M, Morris RG, Nashef L, Richardson MP. Impaired cognitive function in idiopathic generalized epilepsy and unaffected family members: an epilepsy endophenotype. Epilepsia. 2014;55(6):835–40.  https://doi.org/10.1111/epi.12604.CrossRefPubMedGoogle Scholar
  61. 61.
    Hosmer DW, Lemeshow S. Chapter 5. Assessing the fit of the model. Applied Logistic Regression, 2nd Ed. Wiley 2000.Google Scholar
  62. 62.
    Mamede M, Ishizu K, Ueda M, Mukai T, Iida Y, Fukuyama H, et al. Quantification of human nicotinic acetylcholine receptors with 123I-5IA SPECT. J Nucl Med. 2004;45(9):1458–70.PubMedGoogle Scholar
  63. 63.
    Horti AG, Kuwabara H, Holt DP, Dannals RF, Wong DF. Recent PET radioligands with optimal brain kinetics for imaging nicotinic acetylcholine receptors. J Labelled Comp Radiopharm. 2013;56(3-4):159–66.  https://doi.org/10.1002/jlcr.3020.CrossRefPubMedGoogle Scholar
  64. 64.
    Lagarde J, Sarazin M, Chauvire V, Stankoff B, Kas A, Lacomblez L, et al. Cholinergic changes in aging and Alzheimer disease: an [18F]-F-A-85380 exploratory PET study. Alzheimer Dis Assoc Disord. 2017;31(1):8–12.  https://doi.org/10.1097/WAD.0000000000000163.CrossRefPubMedGoogle Scholar
  65. 65.
    Picard F, Bertrand S, Steinlein OK, Bertrand D. Mutated nicotinic receptors responsible for autosomal dominant nocturnal frontal lobe epilepsy are more sensitive to carbamazepine. Epilepsia. 1999;40(9):1198–209.CrossRefGoogle Scholar
  66. 66.
    Zheng C, Yang K, Liu Q, Wang MY, Shen J, Valles AS, et al. The anticonvulsive drug lamotrigine blocks neuronal {alpha}4{beta}2 nicotinic acetylcholine receptors. J Pharmacol Exp Ther. 2010;335(2):401–8.  https://doi.org/10.1124/jpet.110.171108.CrossRefPubMedGoogle Scholar
  67. 67.
    da Silva Braga AM, Fujisao EK, Betting LE. Analysis of generalized interictal discharges using quantitative EEG. Epilepsy Res. 2014;108(10):1740–7.  https://doi.org/10.1016/j.eplepsyres.2014.09.004.CrossRefPubMedGoogle Scholar
  68. 68.
    Szaflarski JP, DiFrancesco M, Hirschauer T, Banks C, Privitera MD, Gotman J, et al. Cortical and subcortical contributions to absence seizure onset examined with EEG/fMRI. Epilepsy Behav. 2010;18(4):404–13.  https://doi.org/10.1016/j.yebeh.2010.05.009.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Nuclear Medicine and Molecular Imaging Division, Department of Medical ImagingUniversity Hospitals of GenevaGenève 14Switzerland
  2. 2.Faculty of MedicineGeneva UniversityGenevaSwitzerland
  3. 3.Advantis Medical ImagingEindhovenThe Netherlands
  4. 4.EEG and Epilepsy Unit, Department of NeurologyUniversity Hospitals of GenevaGenève 14Switzerland
  5. 5.CIRD - Centre d’Imagerie Rive DroiteGenèveSwitzerland
  6. 6.Department of Surgical Sciences, RadiologyUppsala UniversityUppsalaSweden

Personalised recommendations