Epileptic seizure development

Figure 16.3 Changes in neuronal function required for the development of epileptic seizures. The factors that may control or induce the changes in neuronal function that turn a normal neuron into a focal one (A) recruit other neurons (focal epileptogenesis) to produce an interictal EEG spike (B) and ensure the spread of activity (general epileptogenesis) to full ictal activity (C) are discussed in the text. They include alterations to various ion channels, especially those for Na, a reduction in local inhibitory activity or an increase in local excitatory drive. The electrophysiological counterparts of some of the events involved are shown in Fig. 16.2...

There is no shortage of AEDs (Fig. 16.7) but it is not appropriate to consider them in detail in this text other than to see how their mechanisms of action comply with and illustrate those proposed above (Fig. 16.6) for the control of epileptic seizures (see Meldrum 1996 Upton 1994). The decision on which drug to use depends not only on their proven efficacy in a particular type of epilepsy (some drugs are inactive in certain forms) but also what side-effects they have—many are sedative — how they interact with other drugs and how often they need to be taken. Compliance is a problem over a long period if dosing is required more than once a day. It is probably acceptable in reality, if not scientifically, to divide the drugs into old-established AEDs and new AEDs. Only the latter have been developed chemically to modify the known synaptic function of the amino acids. 

Two Scandinavian patients taking combinations of neuroleptic drugs and tricyclic antidepressants developed epileptic seizures (194). The risk of seizures is greater in patients with brain damage or epilepsy and with high dosages, sudden increases in dosage, or shortly after the introduction of a second compound. 

Picrotoxin and coriaria lactone (mainly a mixture of tutin (11) and coriamyrtin (9)) as well as many other picrotoxanes, are epileptogenic compormds and they are used to induce epilepsy in laboratory animals to test newly developed antiepileptic compounds (259). Their importance may be seen from the fact that recent estimations show that 0.4—1 % of the population suffers from epileptic seizures, with one-third of the sufferers being younger than 16-years-old, and that the average duration of the disease is 12.5 to 25 years 260). 

In 2002, Kwan and Brodie proposed the P-gp positive seizure axis. This theory suggests that expression of ABCBl is a progressive process that depends on intensity and time constancy of seizure injury. It was found in a cohort of 52 5 epileptic patients that the number of patients who develop RE directly correlates with the number and frequency of epileptic seizures before the onset of drug therapy. 

Mice develop apparently normally in the absence of the CBi receptor. They are fertile, care for their offspring, and do not show any behavioural abnormalities that would be obvious to the casual observer. However, CBi-deficient animals have a much higher mortality rate than wild-type animals (Zimmer et al. 1999). Approximately 30% of the mutant animals die of natural causes during the first 6 months, in contrast to less than 5% of the heterozygous and wild-type control animals. The mortality rate in knockout mice is equally high in animals of different age, and death occurs suddenly without prior evidence of illness. Careful examination of dead animals has not yet revealed a cause of death. However, we have frequently observed epileptic seizures in mutant animals and believe that these may have contributed to the increased mortality rate. 

Not all epileptic seizures can be controlled by conventional therapy, and so new drugs have and are being developed. Some of them already in use are discussed below. 

The link between psyche (mind) and soma (body) was confirmed by a commercially available device to control depression. This device consists of an implantable vagus nerve stimulator (Figure 6.22.13), that, when activated, reduced or eliminated depression episodes (Moore, 2005). The same device had been developed to control epileptic seizures, and joins multiple other electrical neural stimulators to control Parkinson s disease, pain, anxiety, chronic headache, bulimia, and others. 

Goddard, GV (1967) Development of epileptic seizures through brain stimtrlation at low intensity. Nature, 214 1020-1021. 

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