Cellular and Network Mechanisms of Spike‐Wave Seizures

Summary:  Spike‐wave seizures are often considered a relatively “pure” form of epilepsy, with a uniform defect present in all patients and involvement of the whole brain homogenously. Here, we present evidence against these common misconceptions. Rather than a uniform disorder, spike‐wave rhythms arise from the normal inherent network properties of brain excitatory and inhibitory circuits, where they can be provoked by many different insults in several different brain networks. Here we discuss several different cellular and molecular mechanisms that may contribute to the generation of spike‐wave seizures, particularly in idiopathic generalized epilepsy. In addition, we discuss growing evidence that electrical, neuroimaging, and molecular changes in spike‐wave seizures do not involve the entire brain homogenously. Rather, spike‐wave discharges occur selectively in some thalamocortical networks, while sparing others. It is hoped that improved understanding of the heterogeneous defects and selective brain regions involved will ultimately lead to more effective treatments for spike‐wave seizures.

[1]  M. Steriade,et al.  Neocortical seizures: initiation, development and cessation , 2004, Neuroscience.

[2]  D. Tucker,et al.  Are “Generalized” Seizures Truly Generalized? Evidence of Localized Mesial Frontal and Frontopolar Discharges in Absence , 2004, Epilepsia.

[3]  F. Hyder,et al.  Relative Changes in Cerebral Blood Flow and Neuronal Activity in Local Microdomains during Generalized Seizures , 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[4]  M. T. Medina,et al.  Mutations in EFHC1 cause juvenile myoclonic epilepsy , 2004, Nature Genetics.

[5]  J. Noebels,et al.  Elevated Thalamic Low-Voltage-Activated Currents Precede the Onset of Absence Epilepsy in the SNAP25-Deficient Mouse Mutant Coloboma , 2004, The Journal of Neuroscience.

[6]  Fahmeed Hyder,et al.  Dynamic fMRI and EEG Recordings during Spike-Wave Seizures and Generalized Tonic-Clonic Seizures in WAG/Rij Rats , 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[7]  Robert Nitsch,et al.  An impaired neocortical Ih is associated with enhanced excitability and absence epilepsy , 2004, The European journal of neuroscience.

[8]  J. Gotman,et al.  fMRI activation during spike and wave discharges in idiopathic generalized epilepsy. , 2004, Brain : a journal of neurology.

[9]  E. Kimchi,et al.  Dysregulation of sodium channel expression in cortical neurons in a rodent model of absence epilepsy , 2004, Brain Research.

[10]  S. Hughes,et al.  Pathway-Specific Action of γ-Hydroxybutyric Acid in Sensory Thalamus and Its Relevance to Absence Seizures , 2003, The Journal of Neuroscience.

[11]  Anthony B Waites,et al.  fMRI “deactivation” of the posterior cingulate during generalized spike and wave , 2003, NeuroImage.

[12]  E. van Luijtelaar,et al.  Genetic Animal Models for Absence Epilepsy: A Review of the WAG/Rij Strain of Rats , 2003, Behavior genetics.

[13]  Miguel A L Nicolelis,et al.  Behavioral detection of tactile stimuli during 7–12 Hz cortical oscillations in awake rats , 2003, Nature Neuroscience.

[14]  Karl J. Friston,et al.  Functional magnetic resonance imaging of human absence seizures , 2003, Annals of neurology.

[15]  Hal Blumenfeld,et al.  From Molecules to Networks: Cortical/Subcortical Interactions in the Pathophysiology of Idiopathic Generalized Epilepsy , 2003, Epilepsia.

[16]  Knut Holthoff,et al.  Absence epilepsy and sinus dysrhythmia in mice lacking the pacemaker channel HCN2 , 2003, The EMBO journal.

[17]  M. Avoli,et al.  Thalamocortical oscillations in a genetic model of absence seizures , 2002, The European journal of neuroscience.

[18]  F. Hyder,et al.  Cerebral energetics and spiking frequency: The neurophysiological basis of fMRI , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Uwe Runge,et al.  A splice-site mutation in GABRG2 associated with childhood absence epilepsy and febrile convulsions. , 2002, Archives of neurology.

[20]  V. Crunelli,et al.  Childhood absence epilepsy: Genes, channels, neurons and networks , 2002, Nature Reviews Neuroscience.

[21]  F. H. Lopes da Silva,et al.  Cortical Focus Drives Widespread Corticothalamic Networks during Spontaneous Absence Seizures in Rats , 2002, The Journal of Neuroscience.

[22]  Michael G Hanna,et al.  Human epilepsy associated with dysfunction of the brain P/Q-type calcium channel , 2001, The Lancet.

[23]  D. Ulrich,et al.  GABA(B) and NMDA receptors contribute to spindle-like oscillations in rat thalamus in vitro. , 2001, Journal of neurophysiology.

[24]  A. Coenen,et al.  Electrophysiological and pharmacological characteristics of two types of spike-wave discharges in WAG/Rij rats , 2001, Brain Research.

[25]  D. Pinault,et al.  Medium-voltage 5–9-Hz oscillations give rise to spike-and-wave discharges in a genetic model of absence epilepsy: in vivo dual extracellular recording of thalamic relay and reticular neurons , 2001, Neuroscience.

[26]  K. Yamakawa,et al.  Advances in the genetics of progressive myoclonus epilepsy. , 2001, American journal of medical genetics.

[27]  L. Lagae,et al.  De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. , 2001, American journal of human genetics.

[28]  H. Meeren,et al.  Auditory evoked potentials from auditory cortex, medial geniculate nucleus, and inferior colliculus during sleep–wake states and spike-wave discharges in the WAG/Rij rat , 2001, Brain Research.

[29]  M A Rogawski,et al.  Generalized Epileptic Disorders: An Update , 2001, Epilepsia.

[30]  H. Pape,et al.  Contribution of intralaminar thalamic nuclei to spike‐and‐wave‐discharges during spontaneous seizures in a genetic rat model of absence epilepsy , 2001, The European journal of neuroscience.

[31]  A. Destexhe,et al.  Cortical Feedback Controls the Frequency and Synchrony of Oscillations in the Visual Thalamus , 2000, The Journal of Neuroscience.

[32]  G. Kostopoulos,et al.  Spike-and-wave discharges of absence seizures as a transformation of sleep spindles: the continuing development of a hypothesis , 2000, Clinical Neurophysiology.

[33]  M. Avoli,et al.  Spindle-like thalamocortical synchronization in a rat brain slice preparation. , 2000, Journal of neurophysiology.

[34]  D. McCormick,et al.  Corticothalamic Inputs Control the Pattern of Activity Generated in Thalamocortical Networks , 2000, The Journal of Neuroscience.

[35]  C. Yalçınkaya,et al.  Ictal and interictal SPECT findings in childhood absence epilepsy , 2000, Seizure.

[36]  M. Castro-Alamancos,et al.  Neocortical Synchronized Oscillations Induced by Thalamic Disinhibition In Vivo , 1999, The Journal of Neuroscience.

[37]  Erika E. Fanselow,et al.  Behavioral Modulation of Tactile Responses in the Rat Somatosensory System , 1999, The Journal of Neuroscience.

[38]  J. Huguenard,et al.  Reciprocal inhibitory connections and network synchrony in the mammalian thalamus. , 1999, Science.

[39]  B Diehl,et al.  Cerebral Hemodynamic Response to Generalized Spike‐Wave Discharges , 1998, Epilepsia.

[40]  D. Contreras,et al.  Spike-wave complexes and fast components of cortically generated seizures. I. Role of neocortex and thalamus. , 1998, Journal of neurophysiology.

[41]  M Steriade,et al.  Spike-wave complexes and fast components of cortically generated seizures. IV. Paroxysmal fast runs in cortical and thalamic neurons. , 1998, Journal of neurophysiology.

[42]  N Dürmüller,et al.  Role of Thalamic and Cortical Neurons in Augmenting Responses and Self-Sustained Activity: Dual Intracellular Recordings In Vivo , 1998, The Journal of Neuroscience.

[43]  M. Burmeister,et al.  Mutation in AP-3 δ in the mocha Mouse Links Endosomal Transport to Storage Deficiency in Platelets, Melanosomes, and Synaptic Vesicles , 1998, Neuron.

[44]  L. Danober,et al.  Pathophysiological mechanisms of genetic absence epilepsy in the rat , 1998, Progress in Neurobiology.

[45]  H. Meeren,et al.  Cortical and thalamic visual evoked potentials during sleep-wake states and spike-wave discharges in the rat. , 1998, Electroencephalography and clinical neurophysiology.

[46]  T Seidenbecher,et al.  Relations between cortical and thalamic cellular activities during absence seizures in rats , 1998, The European journal of neuroscience.

[47]  Maria V. Sanchez-Vives,et al.  Functional dynamics of GABAergic inhibition in the thalamus. , 1997, Science.

[48]  W. Frankel,et al.  Sodium/Hydrogen Exchanger Gene Defect in Slow-Wave Epilepsy Mutant Mice , 1997, Cell.

[49]  B. Connors,et al.  THALAMOCORTICAL SYNAPSES , 1997, Progress in Neurobiology.

[50]  J. Noebels,et al.  Increased excitability and inward rectification in layer V cortical pyramidal neurons in the epileptic mutant mouse Stargazer. , 1997, Journal of neurophysiology.

[51]  R. Robinson,et al.  Focal abnormalities detected by 18FDG PET in epileptic encephalopathies. , 1996, Archives of disease in childhood.

[52]  D. Brooks,et al.  Demonstration of thalarnic activation during typical absence seizures using H2 15O and PET , 1995, Neurology.

[53]  O. Snead,et al.  Presynaptic gamma-hydroxybutyric acid (GHB) and gamma-aminobutyric acidB (GABAB) receptor-mediated release of GABA and glutamate (GLU) in rat thalamic ventrobasal nucleus (VB): a possible mechanism for the generation of absence-like seizures induced by GHB. , 1995, The Journal of pharmacology and experimental therapeutics.

[54]  O. Snead,et al.  Basic mechanisms of generalized absence seizures , 1995, Annals of neurology.

[55]  A. Agmon,et al.  Oscillatory synaptic interactions between ventroposterior and reticular neurons in mouse thalamus in vitro. , 1994, Journal of neurophysiology.

[56]  J. Hoffman,et al.  Focal Cerebral Metabolic Abnormality in a Patient With Continuous Spike Waves During Slow-Wave Sleep , 1994, Journal of child neurology.

[57]  X. Qiao,et al.  Developmental analysis of hippocampal mossy fiber outgrowth in a mutant mouse with inherited spike-wave seizures , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[58]  T. Sejnowski,et al.  Thalamocortical oscillations in the sleeping and aroused brain. , 1993, Science.

[59]  D. McCormick,et al.  Cellular mechanisms of a synchronized oscillation in the thalamus. , 1993, Science.

[60]  A. Coenen,et al.  Genetic models of absence epilepsy, with emphasis on the WAG/Rij strain of rats , 1992, Epilepsy Research.

[61]  E. van Luijtelaar,et al.  Arousal, performance and absence seizures in rats. , 1991, Electroencephalography and clinical neurophysiology.

[62]  Antoine Depaulis,et al.  Mapping of spontaneous spike and wave discharges in Wistar rats with genetic generalized non-convulsive epilepsy , 1990, Brain Research.

[63]  T. Pedley.  Current Practice of Clinical Electroencephalography , 1990 .

[64]  E. Rodin,et al.  Cerebral electrical fields during petit mal absences. , 1987, Electroencephalography and clinical neurophysiology.

[65]  M Diksic,et al.  Effect of generalized spike‐and‐wave discharge on glucose metabolism measured by positron emission tomography , 1987, Annals of neurology.

[66]  G. Holmes,et al.  Absence seizures in children: Clinical and electroencephalographic features , 1987, Annals of neurology.

[67]  A. Coenen,et al.  Two types of electrocortical paroxysms in an inbred strain of rats , 1986, Neuroscience Letters.

[68]  W H Theodore,et al.  Positron emission tomography in generalized seizures , 1985, Neurology.

[69]  M E Phelps,et al.  Local cerebral metabolic rate for glucose during petit mal absences , 1985, Annals of neurology.

[70]  M E Phelps,et al.  Patterns of human local cerebral glucose metabolism during epileptic seizures. , 1982, Science.

[71]  M. Avoli,et al.  Participation of corticothalamic cells in penicillin-induced generalized spike and wave discharges , 1982, Brain Research.

[72]  Massimo Avoli,et al.  Role of the thalamus in generalized penicillin epilepsy: Observations on decorticated cats , 1982, Experimental Neurology.

[73]  Massimo Avoli,et al.  Interaction of cortex and thalamus in spike and wave discharges of feline generalized penicillin epilepsy , 1982, Experimental Neurology.

[74]  P. Gloor,et al.  The Effects of Transient Functional Depression of the Thalamus on Spindles and on Bilateral Synchronous Epileptic Discharges of Feline Generalized Penicillin Epilepsy , 1981, Epilepsia.

[75]  J. Gotman,et al.  A study of the transition from spindles to spike and wave discharge in feline generalized penicillin epilepsy: Microphysiological features , 1981, Experimental Neurology.

[76]  P. Gloor,et al.  Role of afferent input of subcortical origin in the genesis of bilaterally synchronous epileptic discharges of feline generalized penicillin epilepsy , 1979, Experimental Neurology.

[77]  L F Quesney,et al.  Pathophysiology of generalized penicillin epilepsy in the cat: the role of cortical and subcortical structures. II. Topical application of penicillin to the cerebral cortex and to subcortical structures. , 1977, Electroencephalography and clinical neurophysiology.

[78]  M. Steriade,et al.  Cortically elicited spike-wave after discharges in thalamic neurons. , 1976, Electroencephalography and clinical neurophysiology.

[79]  F. Andermann,et al.  Absence Status A Reappraisal following Review of Thirty‐eight Patients , 1972, Epilepsia.

[80]  D. Riche,et al.  Light-induced epilepsy in the baboon, Papio papio: cortical and depth recordings. , 1968, Electroencephalography and clinical neurophysiology.

[81]  F. Gibbs,et al.  The Electro Encephalogram in Epilepsy and in Conditions of Impaired Consciousness , 1968 .

[82]  R. Mutani,et al.  Experimental epilepsy induced by cobalt powder in lower brain-stem and thalamic structures. , 1967, Electroencephalography and clinical neurophysiology.

[83]  B. Weir,et al.  The morphology of the spike-wave complex. , 1965, Electroencephalography and clinical neurophysiology.

[84]  H. Jasper,et al.  The electroencephalogram in parasagittal lesions. , 1952, Electroencephalography and clinical neurophysiology.

[85]  F. Gibbs,et al.  THE ELECTRO-ENCEPHALOGRAM IN EPILEPSY AND IN CONDITIONS OF IMPAIRED CONSCIOUSNESS , 1935 .

[86]  Hans Berger,et al.  Über das Elektrenkephalogramm des Menschen , 1932, Archiv für Psychiatrie und Nervenkrankheiten.

[87]  H. Berger.  Über das Elektrenkephalogramm des Menschen , 1929, Archiv für Psychiatrie und Nervenkrankheiten.

[88]  H. Blumenfeld.  Consciousness and epilepsy: why are patients with absence seizures absent? , 2005, Progress in brain research.

[89]  S. Horvath,et al.  Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies , 2003, Nature Genetics.

[90]  H. Blumenfeld.  The thalamus and seizures. , 2002, Archives of neurology.

[91]  David A. Williams,et al.  Mutant GABAA receptor γ2-subunit in childhood absence epilepsy and febrile seizures , 2001, Nature Genetics.

[92]  D. McCormick,et al.  On the cellular and network bases of epileptic seizures. , 2001, Annual review of physiology.

[93]  I. Scheffer,et al.  Mutant GABA(A) receptor gamma2-subunit in childhood absence epilepsy and febrile seizures. , 2001, Nature genetics.

[94]  T. Sejnowski,et al.  Thalamic and thalamocortical mechanisms underlying 3 Hz spike-and-wave discharges. , 1999, Progress in brain research.

[95]  D. McCormick,et al.  Sleep and arousal: thalamocortical mechanisms. , 1997, Annual review of neuroscience.

[96]  D R Fish,et al.  Demonstration of thalamic activation during typical absence seizures using H2(15)O and PET. , 1995, Neurology.

[97]  D. McCormick,et al.  From Cellular to Network Mechanisms of a Thalamic Synchronized Oscillation , 1994 .

[98]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[99]  V. Voiculescu,et al.  Centrencephalic epilepsy induced by cobalt in the brain stem reticular formation. , 1971, Revue roumaine de neurologie.

[100]  R. Morison,et al.  MECHANISM OF THALAMOCORTICAL AUGMENTATION AND REPETITION , 1943 .