Chapter 3 Seizure Disorders and Epilepsy From Diseases of the Nervous System. Copyright © 2015 Elsevier Inc. All rights reserved.

Figure 1 In hospital electroencephalography (EEG) recording (A) Figure 1 In hospital electroencephalography (EEG) recording (A). Placement of EEG electrodes according to the 10–20 international system is the standard naming and positioning scheme for EEG applications. It is based on an iterative subdivision of arcs on the scalp starting from craniometric reference points: nasion (Ns), inion (In), left preauricular (PAL) and right preauricular (PAR) points (B). The intersection of the longitudinal (Ns–In) and lateral (PAL–PAR) is called the vertex. http://www.bci2000.org/wiki/index.php/User_Tutorial:EEG_Measurement_Setup. From Diseases of the Nervous System. Copyright © 2015 Elsevier Inc. All rights reserved. 2

Figure 2 Example electroencephalography (EEG) recording of a focal seizure originating from the right temporal lobe (top) and a generalized absence seizure (bottom). Typical 3-Hz spike and wave discharges are seen. Courtesy of Jerzy P. Szaflarski, MD, PhD, University of Alabama Epilepsy Center. From Diseases of the Nervous System. Copyright © 2015 Elsevier Inc. All rights reserved. 3

Figure 3 Schematized arrangement of excitatory pyramidal cells (blue) and their interactions with inhibitory GABAergic interneurons (orange). A synchronous release of GABAergic inhibition may lead the network to act as pacemaker. From Diseases of the Nervous System. Copyright © 2015 Elsevier Inc. All rights reserved. 4

Figure 4 Hippocampus showing mossy fibers sprouting, visualized by the dark/black (Timms) staining at low (top) and high magnification (×400; bottom). From Ref. 7. From Diseases of the Nervous System. Copyright © 2015 Elsevier Inc. All rights reserved. 5

Figure 5 Astrocytic recycling of glutamate (Glu) via active transport and subsequent conversion to glutamine (Gln) protect neurons from excessive excitation. From Diseases of the Nervous System. Copyright © 2015 Elsevier Inc. All rights reserved. 6

Reproduced with permission from Ref. 13. Figure 6 Cl− transport affects the action of γ-aminobutyric acid (GABA) as either an inhibitory or excitatory transmitter. In the developing, immature brain, intracellular Cl− is accumulated to a high concentration via the activity of the highly expressed NKCC1 transporter. As a result, GABA acts as an excitatory neurotransmitter (A). Upon maturation, NKCC1 expression is reduced and KCC2 expression now predominates shunting Cl− out of the cell. The resulting low intracellular Cl− makes GABA an inhibitory neurotransmitter. Reproduced with permission from Ref. 13. From Diseases of the Nervous System. Copyright © 2015 Elsevier Inc. All rights reserved. 7

Figure 7 Surgical treatment of epilepsy Figure 7 Surgical treatment of epilepsy. Coronal magnetic resonance image (MRI; fluid-attenuated inversion recovery) of brain before surgery in coronal (A) and axial view before surgery showing right mesial temporal sclerosis (arrows) with compensatory dilatation of the temporal horn before surgery. (C) and (D) show the same views, respectively, of T1-weighted MRI scans images after surgical removal of the amygdala, hippocampus and anterior temporal lobe. From Ref. 21. From Diseases of the Nervous System. Copyright © 2015 Elsevier Inc. All rights reserved. 8

Box 1- Figure 1 Neuronal discharge is the consequence of the activity of Na+ and K+ channels. Their conductance gNa and gK is schematically illustrated for different stimulus conditions. Short subthreshold stimuli fail to elicit an action potential. Threshold stimulation causes single action potentials, whereas suprathreshold stimulation causes multiple action potentials. Sustained, epileptiform discharge can be caused by aberrant K+ clearance or mutations in the underlying ion channels. From Diseases of the Nervous System. Copyright © 2015 Elsevier Inc. All rights reserved. 9

Box 2-Figure 1 Schematic of a synapse Box 2-Figure 1 Schematic of a synapse. The presynaptic arrival of action potentials causes the terminal to depolarize. The resulting activation of presynaptic Ca2+ channels leads to the influx of Ca2+. This leads to presynaptic glutamate (Glu) release which then activates postsynaptic receptors. The resulting postsynaptic depolarization spreads along the dendrite as a graded receptor potential. Excess Glu is being taken up by astrocytes and converted to glutamine (Gln). From Diseases of the Nervous System. Copyright © 2015 Elsevier Inc. All rights reserved. 10

Box 3- Figure 1 Schematized propagation of an electrical signal Box 3- Figure 1 Schematized propagation of an electrical signal. Summazion of excitatory glutamatergic inputs are antagonized by inhibitory GABAergic input. If sufficient activity sums in the axon initial segment, an action potential propagates down the axon. From Diseases of the Nervous System. Copyright © 2015 Elsevier Inc. All rights reserved. 11