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Additional resources for Epilepsy and the Ketogenic Diet: Clinical Implementation & the Scientific Basis (Nutrition and Health)
Such discharges in one neuron can easily spread to others, overwhelming the inhibitory control on the system and leading to an electrographic and clinical seizure. This interictal-to-ictal transition may occur because the post-PDS hyperpolarization is diminished owing to potentiation of EPSPs, decrement in IPSPs, inability to clear extracellular K+, a large increase in intracellular calcium, or a variety of other mechanisms. 3. Seizure Propagation The exact mechanisms by which seizure activity spreads from its focus of origin to distant parts of the brain are less well understood but are likely to involve similar physiologic processes (38).
1. Hyperexcitability and Hypersynchrony: Hallmarks of Epileptic Neurons How is normal neuronal ﬁring altered in epilepsy? The pathophysiology of epilepsy has two distinct but related hallmarks: hyperexcitability and hypersynchrony (33,34). Hyperexcitability is the abnormal responsiveness of a neuron to an excitatory input; the neuron tends to ﬁre multiple discharges instead of the usual one or two. Hypersyn- Chapter 1 / Seizures and Epilepsy 17 Table 3 Roles of Channels and Receptors in Normal and Epileptic Firing Channel or receptor Voltage-gated Na+ channel Voltage-gated K+ channel Ca2+-dependent K+ channel Voltage-gated Ca2+ channel Non-NMDA receptor NMDA receptor GABAA receptor GABAB receptor Electrical synapses Na-K pump Role in normal neuronal function Possible role in epilepsy Subthreshold EPSP; action potential upstroke Action potential downstroke Repetitive action potential ﬁring Abnormal action potential repolarization AHP following action potential; Limits repetitive ﬁring sets refractory period Transmitter release; carries Excess transmitter release; depolarizing charge from activates pathologic dendrites to soma intracellular processes Fast EPSP Initiates paroxysmal depolarization shift (PDS) Prolonged, slow EPSP Maintains PDS; Ca2+ activates pathological intracellular processes IPSP Limits excitation Prolonged IPSP Limits excitation Ultrafast excitatory Synchronization of transmission neuronal ﬁring Restores ionic balance Prevents K+-induced depolarization chrony refers to the recruitment of large numbers of neighboring neurons into an abnormal ﬁring pattern.
Positron emission tomography and single photon emission computed tomography in epilepsy care. Semin Nucl Med 2003;33:88–104. 8. Otsubo H, Snead OC III. Magnetoencephalography and magnetic source imaging in children. J Child Neurol 2001;16:227–235. 9. Nordli DR, DeVivo DC. Classiﬁcation of infantile seizures: implications for identiﬁcation and treatment of inborn errors of metabolism. J Child Neurol 2002;17 (Suppl 3):3S15–3S23. 10. Kwan P, Brodie MJ. Early identiﬁcation of refractory epilepsy. N Engl J Med 2000;342:314–319.