Open AccessJournal Article
Pathophysiology of epilepsy
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TLDR
New insights point to alterations of synaptic functions and intrinsic properties of neurons as common mechanisms underlying hyperexcitability in epilepsy, as well as mechanisms involved in interictal-ictal transition.Abstract:
This work reviews the current knowledge on epileptogenesis and pathophysiology of epilepsy. Recently, gene defects underlying four monogenic epilepsies (generalized epilepsy with febrile seizures, autosomal dominant nocturnal frontal lobe epilepsy, benign familial neonatal convulsions and episodic ataxia type 1 with partial seizures) have been identified, shedding new light on the pathophysiology of epilepsy as these diseases are caused by ion channel mutations. Although epileptic syndromes differ pathophysiologically, common ictogenesis-related characteristics as increased neuronal excitability and synchronicity are shared as well as mechanisms involved in interictal-ictal transition. Emerging insights point to alterations of synaptic functions and intrinsic properties of neurons as common mechanisms underlying hyperexcitability. This work also reviews the neurochemical mechanisms of epilepsy. An imbalance between glutamate and gamma-aminobutyric acid neurotransmitter systems can lead to hyperexcitability but catecholaminergic neurotransmitter systems and opioid peptides were shown to play a role in epileptogenesis as well. An overview of currently available anti-epileptic drugs and their presumed mechanisms of action is given as an illustration of the neurochemistry of epileptogenesis. Most anti-epileptic drugs exert their anti-epileptic properties through only a few neurochemical mechanisms that are meanwhile basic pathophysiological mechanisms thought to cause seizures.read more
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Probing and regulating dysfunctional circuits using deep brain stimulation.
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TL;DR: Recent advances in the DBS field are reviewed and potential future directions in targeted intracranial neuromodulation are discussed, making it a powerful tool to study the human brain.
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Network and pharmacological mechanisms leading to epileptiform synchronization in the limbic system in vitro.
Massimo Avoli,Margherita D'Antuono,Jacques Louvel,Rüdiger Köhling,Giuseppe Biagini,René Pumain,Giovanna D'Arcangelo,Virginia Tancredi +7 more
TL;DR: Experimental evidence obtained in combined hippocampus-entorhinal cortex slices perfused with artificial cerebrospinal fluid containing convulsants or nominally zero Mg(2+), in order to produce epileptiform synchronization indicates that these changes in network interactions, along with other mechanisms of synaptic plasticity can confer to the epileptic, damaged limbic system, the ability to produce recurrent limbic seizures.
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The adenosine kinase hypothesis of epileptogenesis
TL;DR: ADK emerges both as a diagnostic marker to predict, as well as a prime therapeutic target to prevent, epileptogenesis.
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Heterogeneous neuronal firing patterns during interictal epileptiform discharges in the human cortex
Corey J. Keller,Wilson Truccolo,Wilson Truccolo,John T. Gale,Emad N. Eskandar,Thomas Thesen,Chad Carlson,Orrin Devinsky,Ruben Kuzniecky,Werner Doyle,Joseph R. Madsen,Donald L. Schomer,Ashesh D. Mehta,Emery N. Brown,Leigh R. Hochberg,István Ulbert,István Ulbert,Eric Halgren,Sydney S. Cash +18 more
TL;DR: Heterogeneity in single unit activity was present within small cortical regions as well as inside and outside the seizure onset zone, suggesting that interictal epileptiform activity in patients with epilepsy is not a simple paroxysm of hypersynchronous excitatory activity, but rather represents an interplay of multiple distinct neuronal types within complex neuronal networks.
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Protective effect of safranal on pentylenetetrazol-induced seizures in the rat: Involvement of GABAergic and opioids systems
TL;DR: It is demonstrated that safranal could exert anticonvulsant activity in the PTZ model and this effect may be mediated, at least partly, through GABA(A)-benzodiazepine receptor complex.
References
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Journal ArticleDOI
Mossy fiber synaptic reorganization in the epileptic human temporal lobe.
TL;DR: The results are morphological evidence of mossy Fiber synaptic reorganization in the temporal lobe of epileptic humans, and suggest the intriguing possibility that mossy fiber sprouting and synaptic reorganizing induced by repeated partial complex seizures may play a role in human epilepsy.
Journal ArticleDOI
A Potassium Channel Mutation in Neonatal Human Epilepsy
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TL;DR: Impairment of potassium-dependent repolarization is likely to cause this age-specific epileptic syndrome.
Journal ArticleDOI
A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy.
Ortrud K. Steinlein,John C. Mulley,Peter Propping,Robyn H. Wallace,Robyn H. Wallace,H.A. Phillips,Grant R. Sutherland,Grant R. Sutherland,Ingrid E. Scheffer,Ingrid E. Scheffer,Samuel F. Berkovic,Samuel F. Berkovic +11 more
TL;DR: A missense mutation that replaces serine with phenylalanine at codon 248, a strongly conserved amino acid residue in the second transmembrane domain is found in all 21 available affected family members and in four obligate carriers, but not in 333 healthy control subjects.
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Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B.
Robyn H. Wallace,Dao W. Wang,Rita Singh,Rita Singh,Ingrid E. Scheffer,Ingrid E. Scheffer,Ingrid E. Scheffer,Alfred L. George,H.A. Phillips,Kathrin Saar,André Reis,Eric W. Johnson,Grant R. Sutherland,Grant R. Sutherland,Samuel F. Berkovic,Samuel F. Berkovic,John C. Mulley,John C. Mulley +17 more
TL;DR: It is shown that co-expression of the mutant ß1 subunit with a brain Na+-channel ß subunit in Xenopus laevis oocytes demonstrates that the mutation interferes with the ability of the subunit to modulate channel-gating kinetics consistent with a loss-of-function allele, developing the theme that idiopathic epilepsies are a family of channelopathies.
Journal ArticleDOI
doublecortin, a Brain-Specific Gene Mutated in Human X-Linked Lissencephaly and Double Cortex Syndrome, Encodes a Putative Signaling Protein
Joseph G. Gleeson,Joseph G. Gleeson,Kristina M. Allen,Jeremy W. Fox,Edward D Lamperti,Samuel F. Berkovic,Ingrid E. Scheffer,Edward C. Cooper,William B. Dobyns,Sharon R. Minnerath,M. Elizabeth Ross,Christopher A. Walsh +11 more
TL;DR: A novel 10 kb brain-specific cDNA interrupted by a balanced translocation in an XLIS patient that encodes a novel 40 kDa predicted protein named Doublecortin, which may define an Abl-dependent pathway regulating neuronal migration.