Skip to main content
SpringerLink
Log in

Is There Such a Thing as “Generalized” Epilepsy?

  • Chapter
  • First Online:
Issues in Clinical Epileptology: A View from the Bench

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 813))

Abstract

The distinction between generalized and partial epilepsies is probably one, if not the most, pregnant assertions in modern epileptology. Both absence and generalized tonic-clonic seizures, the prototypic seizures found in generalized epilepsies, are classically seen as the result of a rapid, synchronous recruitment of neuronal networks resulting in impairment of consciousness and/or convulsive semiology. The term generalized also refers to electroencephalographic presentation, with bilateral, synchronous activity, such as the classical 3 Hz spike and wave discharges of typical absence epilepsy. However, findings obtained from electrophysiological and functional imaging studies over the last few years, contradict this view, showing a rather focal onset for most of the so-called generalized seizure types. Therefore, we ask here the question whether “generalized epilepsy” does indeed exist.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Aghakhani Y, Bagshaw AP, Benar CG, Hawco C, Andermann F, Dubeau F et al (2004) fMRI activation during spike and wave discharges in idiopathic generalized epilepsy. Brain J Neurol 127(Pt 5):1127–1144

    Article  CAS  Google Scholar 

  2. Amor F, Baillet S, Navarro V, Adam C, Martinerie J, Quyen MV (2009) Cortical local and long-range synchronization interplay in human absence seizure initiation. NeuroImage 45(3):950–962

    Article  PubMed  Google Scholar 

  3. Archer JS, Abbott DF, Waites AB, Jackson GD (2003) fMRI “deactivation” of the posterior cingulate during generalized spike and wave. NeuroImage 20(4):1915–1922

    Article  PubMed  Google Scholar 

  4. Avoli M (2012) A brief history on the oscillating roles of thalamus and cortex in absence seizures. Epilepsia 53(5):779–789

    Article  PubMed  Google Scholar 

  5. Bal T, von Krosigk M, McCormick DA (1995) Synaptic and membrane mechanisms underlying synchronized oscillations in the ferret lateral geniculate nucleus in vitro. J Physiol 483(Pt 3):641–663

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde BW et al (2010) Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia 51(4):676–685

    Article  PubMed  Google Scholar 

  7. Berger H (1933) Über das Elektrenkephalogramm des Menschen. Arch Für Psychiatr Nervenkrankh 100(1):301–320

    Article  Google Scholar 

  8. Bessaih T, Bourgeais L, Badiu CI, Carter DA, Toth TI, Ruano D et al (2006) Nucleus-specific abnormalities of GABAergic synaptic transmission in a genetic model of absence seizures. J Neurophysiol 96(6):3074–3081

    Article  CAS  PubMed  Google Scholar 

  9. Blumenfeld H, McCormick DA (2000) Corticothalamic inputs control the pattern of activity generated in thalamocortical networks. J Neurosci Off J Soc Neurosci 20(13):5153–5162

    CAS  Google Scholar 

  10. Blumenfeld H, Westerveld M, Ostroff RB, Vanderhill SD, Freeman J, Necochea A et al (2003) Selective frontal, parietal, and temporal networks in generalized seizures. NeuroImage 19(4):1556–1566

    Article  PubMed  Google Scholar 

  11. Carney PW, Masterton RA, Harvey AS, Scheffer IE, Berkovic SF, Jackson GD (2010) The core network in absence epilepsy. Differences in cortical and thalamic BOLD response. Neurology 75(10):904–911

    Article  CAS  PubMed  Google Scholar 

  12. Chugani HT, Shields WD, Shewmon DA, Olson DM, Phelps ME, Peacock WJ (1990) Infantile spasms: I. PET identifies focal cortical dysgenesis in cryptogenic cases for surgical treatment. Ann Neurol 27(4):406–413

    Article  CAS  PubMed  Google Scholar 

  13. Danober L, Deransart C, Depaulis A, Vergnes M, Marescaux C (1998) Pathophysiological mechanisms of genetic absence epilepsy in the rat. Prog Neurobiol 55(1):27–57

    Article  CAS  PubMed  Google Scholar 

  14. Deschenes M, Paradis M, Roy JP, Steriade M (1984) Electrophysiology of neurons of lateral thalamic nuclei in cat: resting properties and burst discharges. J Neurophysiol 51(6):1196–1219

    CAS  PubMed  Google Scholar 

  15. Engel J Jr (2006) Report of the ILAE classification core group. Epilepsia 47(9):1558–1568

    Article  PubMed  Google Scholar 

  16. Engel J Jr, International League Against E (2001) A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia 42(6):796–803

    Article  PubMed  Google Scholar 

  17. Fame RM, MacDonald JL, Macklis JD (2011) Development, specification, and diversity of callosal projection neurons. Trends Neurosci 34(1):41–50

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Fischer-Williams M, Poncet M, Riche D, Naquet R (1968) Light-induced epilepsy in the baboon, Papio papio: cortical and depth recordings. Electroencephalogr Clin Neurophysiol 25(6):557–569

    Article  CAS  PubMed  Google Scholar 

  19. Gastaut H (1969) Clinical and electroencephalographical classification of epileptic seizures. Epilepsia 10(Suppl):2–13

    Google Scholar 

  20. Gastaut H, Gastaut Y, Roger J, Roger A (1955) Statistical study of the different electroclinical types of epilepsy. Marseille Med 92(10):653–662

    CAS  PubMed  Google Scholar 

  21. Gotman J (1987) Interhemispheric interactions in seizures of focal onset: data from human intracranial recordings. Electroencephalogr Clin Neurophysiol 67(2):120–133

    Article  CAS  PubMed  Google Scholar 

  22. Gotman J, Grova C, Bagshaw A, Kobayashi E, Aghakhani Y, Dubeau F (2005) Generalized epileptic discharges show thalamocortical activation and suspension of the default state of the brain. Proc Natl Acad Sci U S A 102(42):15236–15240

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Guevara R, Velazquez JL, Nenadovic V, Wennberg R, Senjanovic G, Dominguez LG (2005) Phase synchronization measurements using electroencephalographic recordings: what can we really say about neuronal synchrony? Neuroinformatics 3(4):301–314

    Article  PubMed  Google Scholar 

  24. Gupta D, Ossenblok P, van Luijtelaar G (2011) Space-time network connectivity and cortical activations preceding spike wave discharges in human absence epilepsy: a MEG study. Med Biol Eng Comput 49(5):555–565

    Article  PubMed  Google Scholar 

  25. Hamandi K, Salek-Haddadi A, Laufs H, Liston A, Friston K, Fish DR et al (2006) EEG-fMRI of idiopathic and secondarily generalized epilepsies. NeuroImage 31(4):1700–1710

    Article  PubMed  Google Scholar 

  26. Hirsch E, Panayiotopoulos T (2005) Childhood absence epilepsy and related syndromes. In: Roger J, Bureau M, Genton P, Tassinari C, Wolf P (eds) Epileptic syndromes in infancy, childhood, and adolescence. John Libbey Eurotext, Paris, pp 315–335

    Google Scholar 

  27. Holmes MD, Brown M, Tucker DM (2004) Are “generalized” seizures truly generalized? Evidence of localized mesial frontal and frontopolar discharges in absence. Epilepsia 45(12):1568–1579

    Article  PubMed  Google Scholar 

  28. Holmes MD, Quiring J, Tucker DM (2010) Evidence that juvenile myoclonic epilepsy is a disorder of frontotemporal corticothalamic networks. NeuroImage 49(1):80–93

    Article  PubMed  Google Scholar 

  29. Huguenard JR, McCormick DA (2007) Thalamic synchrony and dynamic regulation of global forebrain oscillations. Trends Neurosci 30(7):350–356

    Article  CAS  PubMed  Google Scholar 

  30. Izhikevich EM, Edelman GM (2008) Large-scale model of mammalian thalamocortical systems. Proc Natl Acad Sci U S A 105(9):3593–3598

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Jahnsen H, Llinas R (1984) Electrophysiological properties of guinea-pig thalamic neurones: an in vitro study. J Physiol 349:205–226

    CAS  PubMed Central  PubMed  Google Scholar 

  32. Jahnsen H, Llinas R (1984) Ionic basis for the electro-responsiveness and oscillatory properties of guinea-pig thalamic neurones in vitro. J Physiol 349:227–247

    CAS  PubMed Central  PubMed  Google Scholar 

  33. Janz D (1985) Epilepsy with impulsive petit mal (juvenile myoclonic epilepsy). Acta Neurol Scand 72(5):449–459

    Article  CAS  PubMed  Google Scholar 

  34. Jasper H, Droogleever-Fortuyn J (1946) Experimental studies on the functional anatomy of petit mal epilepsy. Res Publ Assoc Res Nerv Ment Dis 26:272–298

    Google Scholar 

  35. Kostopoulos GK (2000) Spike-and-wave discharges of absence seizures as a transformation of sleep spindles: the continuing development of a hypothesis. Clin Neurophysiol 111(Suppl 2):S27–S38

    Article  PubMed  Google Scholar 

  36. Le Van Quyen M, Foucher J, Lachaux J, Rodriguez E, Lutz A, Martinerie J et al (2001) Comparison of Hilbert transform and wavelet methods for the analysis of neuronal synchrony. J Neurosci Methods 111(2):83–98

    Article  Google Scholar 

  37. Lhatoo S, Lüders H (2006) The semiology and pathophysiology of the secondary generalized tonic-clonic seizures. In: Hirsch E, Andermann F, Chauvel P, Engel J, Lopes da Silva F, Lüders H (eds) Generalized seizures: from clinical phenomenology to underlying systems and networks. John Libbey Eurotext, Montrouge, pp 229–245

    Google Scholar 

  38. Liao W, Zhang Z, Mantini D, Xu Q, Ji GJ, Zhang H et al (2013) Dynamical intrinsic functional architecture of the brain during absence seizures. Brain Struct Funct. doi:10.1007/s00429-013-0619-2

  39. Lombroso CT (1997) Consistent EEG, focalities detected in subjects with primary generalized epilepsies monitored for two decades. Epilepsia 38(7):797–812

    Article  CAS  PubMed  Google Scholar 

  40. Manning JP, Richards DA, Leresche N, Crunelli V, Bowery NG (2004) Cortical-area specific block of genetically determined absence seizures by ethosuximide. Neuroscience 123(1):5–9

    Article  CAS  PubMed  Google Scholar 

  41. Marcus EM, Watson CW (1966) Bilateral synchronous spike wave electrographic patterns in the cat. Interaction of bilateral cortical foci in the intact, the bilateral cortical-callosal, and adiencephalic preparation. Arch Neurol 14(6):601–610

    Article  CAS  PubMed  Google Scholar 

  42. Marcus EM, Watson CW (1968) Symmetrical epileptogenic foci in monkey cerebral cortex. Mechanisms of interaction and regional variations in capacity for synchronous discharges. Arch Neurol 19(1):99–116

    Article  CAS  PubMed  Google Scholar 

  43. Marescaux C, Vergnes M, Depaulis A (1992) Genetic absence epilepsy in rats from Strasbourg – a review. J Neural Transm Suppl 35:37–69

    CAS  PubMed  Google Scholar 

  44. Meencke HJ, Janz D (1984) Neuropathological findings in primary generalized epilepsy: a study of eight cases. Epilepsia 25(1):8–21

    Article  CAS  PubMed  Google Scholar 

  45. Meeren HK, Pijn JP, Van Luijtelaar EL, Coenen AM, Lopes da Silva FH (2002) Cortical focus drives widespread corticothalamic networks during spontaneous absence seizures in rats. J Neurosci 22(4):1480–1495

    CAS  PubMed  Google Scholar 

  46. Moeller F, Stephani U, Siniatchkin M (2013) Simultaneous EEG and fMRI recordings (EEG-fMRI) in children with epilepsy. Epilepsia 54(6):971–982

    Article  PubMed  Google Scholar 

  47. Moruzzi G, Magoun HW (1949) Brain stem reticular formation and activation of the EEG. Electroencephalogr Clin Neurophysiol 1(4):455–473

    Article  CAS  PubMed  Google Scholar 

  48. Musgrave J, Gloor P (1980) The role of the corpus callosum in bilateral interhemispheric synchrony of spike and wave discharge in feline generalized penicillin epilepsy. Epilepsia 21(4):369–378

    Article  CAS  PubMed  Google Scholar 

  49. Myoclonus and epilepsy in childhood. Commission on Pediatric Epilepsy of the International League Against Epilepsy (1997) Epilepsia 38(11):1251–1254

    Google Scholar 

  50. Niedermeyer E (1996) Primary (idiopathic) generalized epilepsy and underlying mechanisms. Clin EEG 27(1):1–21

    CAS  Google Scholar 

  51. Panzica F, Rubboli G, Franceschetti S, Avanzini G, Meletti S, Pozzi A et al (2001) Cortical myoclonus in Janz syndrome. Clin Neurophysiol 112(10):1803–1809

    Article  CAS  PubMed  Google Scholar 

  52. Parri HR, Crunelli V (1998) Sodium current in rat and cat thalamocortical neurons: role of a non-inactivating component in tonic and burst firing. J Neurosci 18(3):854–867

    CAS  PubMed  Google Scholar 

  53. Penfield W (ed) (1957) Consciousness and centrencephalic organization. Premier Congres International des Sciences Neurologiques, Bruxelles

    Google Scholar 

  54. Pinault D, Leresche N, Charpier S, Deniau JM, Marescaux C, Vergnes M et al (1998) Intracellular recordings in thalamic neurones during spontaneous spike and wave discharges in rats with absence epilepsy. J Physiol 509(Pt 2):449–456

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Prince DA, Farrell D (1969) “Centrencephalic” spike wave discharges following parenteral penicillin injection in the cat. Neurology 19:309–310

    Google Scholar 

  56. Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy (1989) Epilepsia 30(4):389–399

    Google Scholar 

  57. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the Commission on Classification and Terminology of the International League Against Epilepsy (1981) Epilepsia 22(4):489–501

    Google Scholar 

  58. Rodin E, Ancheta O (1987) Cerebral electrical fields during petit mal absences. Electroencephalogr Clin Neurophysiol 66(6):457–466

    Article  CAS  PubMed  Google Scholar 

  59. Salek-Haddadi A, Lemieux L, Merschhemke M, Friston KJ, Duncan JS, Fish DR (2003) Functional magnetic resonance imaging of human absence seizures. Ann Neurol 53(5):663–667

    Article  PubMed  Google Scholar 

  60. Stefan H, Lopes da Silva FH (2013) Epileptic neuronal networks: methods of identification and clinical relevance. Front Neurol 4:8

    Article  PubMed Central  PubMed  Google Scholar 

  61. Steriade M (2001) The GABAergic reticular nucleus: a preferential target of corticothalamic projections. Proc Natl Acad Sci U S A 98(7):3625–3627

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Steriade M, Contreras D (1995) Relations between cortical and thalamic cellular events during transition from sleep patterns to paroxysmal activity. J Neurosci Off J Soc Neurosci 15(1 Pt 2):623–642

    CAS  Google Scholar 

  63. Swartz BE, Simpkins F, Halgren E, Mandelkern M, Brown C, Krisdakumtorn T et al (1996) Visual working memory in primary generalized epilepsy: an 18FDG-PET study. Neurology 47(5):1203–1212

    Article  CAS  PubMed  Google Scholar 

  64. Taylor J, Holmes GS, Walshe FS (1931) Selected writings of John Hughlings Jackson. Hodder and Stoughton, London

    Google Scholar 

  65. Tenney JR, Fujiwara H, Horn PS, Jacobson SE, Glauser TA, Rose DF (2013) Focal corticothalamic sources during generalized absence seizures: a MEG study. Epilepsy Res 106(1–2):113–122. doi:10.1016/j.eplepsyres.2013.05.006

  66. Tromp D. University of Wisconsin-Madison. http://brainimaging.waisman.wisc.edu/~tromp/resources.html#images

  67. Tsakiridou E, Bertollini L, de Curtis M, Avanzini G, Pape HC (1995) Selective increase in T-type calcium conductance of reticular thalamic neurons in a rat model of absence epilepsy. J Neurosci Off J Soc Neurosci 15(4):3110–3117

    CAS  Google Scholar 

  68. van Luijtelaar EL, Coenen AM (1986) Two types of electrocortical paroxysms in an inbred strain of rats. Neurosci Lett 70(3):393–397

    Article  PubMed  Google Scholar 

  69. van Luijtelaar G, Sitnikova E (2006) Global and focal aspects of absence epilepsy: the contribution of genetic models. Neurosci Biobehav Rev 30(7):983–1003. doi:10.1016/j.neubiorev.2006.03.002

  70. van Luijtelaar G, Sitnikova E, Littjohann A (2011) On the origin and suddenness of absences in genetic absence models. Clin EEG Neurosci 42(2):83–97

    Article  PubMed  Google Scholar 

  71. Veliskova J, Velisek L (2006) Animal models of myoclonic seizures and epilepsies. In: Hirsch E, Andermann F, Chauvel P, Engel J, Lopez da Silva F, Luders H (eds) Generalized seizures: from clinical phenomenology to underlying systems and networks. John Libbey Eurotext, Montrouge, pp 147–161

    Google Scholar 

  72. Vergnes M, Marescaux C, Lannes B, Depaulis A, Micheletti G, Warter JM (1989) Interhemispheric desynchronization of spontaneous spike-wave discharges by corpus callosum transection in rats with petit mal-like epilepsy. Epilepsy Res 4(1):8–13

    Article  CAS  PubMed  Google Scholar 

  73. Vergnes M, Marescaux C, Micheletti G, Reis J, Depaulis A, Rumbach L et al (1982) Spontaneous paroxysmal electroclinical patterns in rat: a model of generalized non-convulsive epilepsy. Neurosci Lett 33(1):97–101

    Article  CAS  PubMed  Google Scholar 

  74. Westmijse I, Ossenblok P, Gunning B, van Luijtelaar G (2009) Onset and propagation of spike and slow wave discharges in human absence epilepsy: a MEG study. Epilepsia 50(12):2538–2548. doi:10.1111/j.1528-1167.2009.02162.x

  75. Yorke CH Jr, Caviness VS Jr (1975) Interhemispheric neocortical connections of the corpus callosum in the normal mouse: a study based on anterograde and retrograde methods. J Comp Neurol 164(2):233–245. doi:10.1002/cne.901640206

Download references

Acknowledgments

We dedicate this manuscript to Phil Schwartzkroin, a friend and colleague, who had a great impact on neurobiological research and on our own studies during the last four decades. He created opportunities for others to promote new concepts and theories. His challenging approach to epilepsy research continues to motivate many of us, and it is indeed mirrored by the question addressed here.

Author information

Authors and Affiliations

  1. Donders Centre for Cognition, Radboud University Nijmegen, Montessorilaan 3, 6525 HR, Nijmegen, The Netherlands

    Gilles van Luijtelaar Ph.D.

  2. Montreal Neurological Institute and Departments of Neurology and Neurosurgery and of Physiology, McGill University, 3801 University Street, Montréal, QC, H3A 2B4, Canada

    Charles Behr M.D. & Massimo Avoli M.D., Ph.D.

  3. Department of Experimental Medicine, Faculty of Medicine and Odontoiatry, Sapienza Università di Roma, Rome, Italy

    Massimo Avoli M.D., Ph.D.

Authors
  1. Gilles van Luijtelaar Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Charles Behr M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Massimo Avoli M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Massimo Avoli M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Dept. of Child & Adoles. Psych., Phys. & Neurosc., and Psych., New York Univ. Langone Med. Ctr., Orangeburg, New York, USA

    Helen E. Scharfman

  2. Dept. of Comp. Med. and Neurol. & Neurol. Scs., Stanford University, Stanford, California, USA

    Paul S. Buckmaster

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

van Luijtelaar, G., Behr, C., Avoli, M. (2014). Is There Such a Thing as “Generalized” Epilepsy?. In: Scharfman, H., Buckmaster, P. (eds) Issues in Clinical Epileptology: A View from the Bench. Advances in Experimental Medicine and Biology, vol 813. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8914-1_7

Download citation

  • DOI: https://doi.org/10.1007/978-94-017-8914-1_7

  • Published:

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-017-8913-4

  • Online ISBN: 978-94-017-8914-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation