PROCESOS DE LA FILTRACIÓN

Epilepsy is a relatively common neurological disorder caused by abnormal discharges in a

collection of neurones (Fisher, 1995). International classification (Dreifuss etaL, 1981) suggests that seizures can be defined as (1) Partial (focal), including simple partial seizures without impairment of consciousness, complex partial seizures with impairment of consciousness and

partial seizures which secondarily generalise. The appearance of the partial (or focal) seizure on EEG (or ECoG) consists of localised spikes and slow wave activity. (2) Generalised seizures of

non-focal origin (convulsive or non-convulsive) include absence seizures, myoclonic seizures, tonic-clonic seizures and tonic seizures. They involve excessive electrical discharges over much of the cerebral cortex. EEG (or ECoG) characteristically present a paradoxical low-voltage

desynchronisation, followed by rhythmical 3 Hz spike-and-slow activity, decelerating to slower frequencies, resolving usually to spike (or spikes) and slow-waves. After the seizure, the background EEG flattens and slows relative to the baseline for several minutes. (3) Unclassified.

Possible pathophysiological mechanisms of epiiepsy: The pathophysiological mechanisms

of epilepsy have been proposed to be (1) decreases in central inhibitory or disinhibition processes and (2) increases in the central excitatory processes or hyperexcitation (Figure 1-13). The current theory concerning the mechanism of epilepsy is reviewed by Fisher (1995). Broadly, there are three principal pathophysiological explanations. (1) Neuronal theory: Epileptic activity is due to alterations in the cell membrane or metabolic properties of individual neurones; (2) Environment theory: Epilepsy is mainly caused by changes in extracellular ion activity (Fisher,

1995; Lux et al., 1986). An imbalance in the extracellular concentration of ions or neural transmitter produces the enhanced neuronal excitation. (3) Aggregation or population theory: Collective anatomic or physiological alterations produce a progressive, network-dependent

facilitation of excitability, perhaps coupled with a decrease of inhibition (Bruehl eta!., 1995). The actual process is likely to be a combination of the above three theories (Fisher, 1995).

Excitation versus inhibition EPSPs _IPSPs Calcium spikes PDS LHP AMP Depolarisation _Pumps

Figure 1-13. Basic mechanisms of epilepsy. Excitation versus inhibition in the CNS are represented as two sides in a balance. On the side of excitation are excitatory postsynaptic potentials (EPSPs), calcium spikes, paroxysmal depolarisation shifts (PDSs), depolarisation from other factors such as increased extracellular potassium and local current flows. On the other side, there are inhibitory postsynaptic potentials (IPSPs), late hyperpolarising potentials (LHPs), after-hyperpolarisations (AMPS), and metabolic pump potentials. Certain forms of seizures occur when excitation is increased relative to inhibition. Modified from Fisher, 1995.

Animal models of epilepsy have been developed for studying mechanisms of epilepsy and

evaluating the efficacy of diagnostic methods and antiepileptic treatments. A variety of models have been developed, but none of the individual models is an exact imitation of clinical epilepsy. Usually a particular type of model is selected specifically to simulate a particular type of seizures (Durand, 1993; Fisher, 1989).

• Acute in vivo models: Acute convulsive discharges can be induced by applying a strong electrical, chemical or thermal stimulus. Such a stimulus usually produces an immediate but short term effect. Epileptic activity only tends to reoccur while the stimulus is repeatedly applied.

(1) Models of chemically-induced focal epilepsy: Focal epileptic discharges have been induced by placing a piece of polyurethane sponge or cotton soaked with chemical drugs on the exposed cortex, such as 1.7 - 3.4 mM penicillin (Avoli, 1995; Bruehl et ai., 1995; de-Feo et al., 1982), Bicuculline (Campbell and Holmes, 1984), Strychnine (Knopman, 1975) or Kainate (Ebisu et ai., 1994). The basic mechanism of penicillin-induced epileptiform discharges is the production of excitatory synaptic potentials due to abolition

of gamma-aminobutyric acid (GABA) - mediated inhibitory processes. This may block the

01 " exchange that normally would carry the ionic current for GABA inhibition (Andersen, 1983; Avoli, 1995). This model is suitable for studying focal seizures with secondary generalisation (de-Feo etaL, 1982).

(2) Models of electrically induced focal epilepsy: Focal electrical discharges can be induced by direct electrical stimulation of the cortex. The major parameters of the electrical stimuli

are 0 . 5 - 1 0 ms square wave pulses, 0.5 - 5 mA in intensity, at frequency of 10 - 100 Hz delivered for a period of 1 - 5s. This model is suitable for partial simple or secondarily

generalised seizures. This focal electrical model has been used to study localisation of the initial discharges and the pathways of secondary spread. One major advantage of this model is that the site of the origin is well defined by position of the stimulating electrode

(Leclercq and Segal, 1965; Marsan, 1972).

(3) A model of focal seizures induced by GABA-withdrawal: Focal seizures can be induced by the effects of GABA-withdrawal after infusing GABA into the motor cortex for a few days (Brailowsky et ai, 1987). This model may, however, confuse the effects of GABA itself with the epileptic discharges (Fisher, 1989).

• Chronic in vivo models: seizures appear with a longer delay but are more permanent. Seizures may reoccur spontaneously.

(1) Traumatic models: Focal cerebral injury can be induced by chronic implantation of metal

materials, such as 4% aluminium hydroxide [AI(0H)3] or other metals (cobalt, tungsten,

zinc or iron). Spontaneous and recurrent seizures occur after one or two months (de-Feo

et al., 1982; Fariello, 1995). Cryogenic or freezing injuries can induce partial simple seizures beginning within a few hours of lesions, and persist for a few days. Systemic injection of epileptogenic drugs or repeated exposure to gases (hyperbaric oxygen) produces seizures (Fenton and Robinson, 1993).

(2) Model of epilepsy induced by chronic electrical stimulation: Repeated electrical shocks on

various parts of brain result in enhanced electrical excitability. After chronic long-term stimulation, areas of the brain may take on epileptic activity independent from the initial electrical stimulation, even if the original stimulation is discontinued. This is termed as

“kindling” (Bertram and Cornett, 1993; Girgis, 1981). During the long experimental period, permanent damages to the brain may occur.

• Models of epilepsy in vitro: These models are extremely useful for pharmacological studies. They are only mentioned here since they are beyond the scope of the present study. Acute partial seizures can be induced in slices of the neocortex (Yamamoto, 1970, Prince and

Wong, 1981) and the hippocampus (McBain et ai., 1989).

Among the above animal models of focal epilepsy, the acute electrical stimulation model appears to be the most suitable model for studying localisation of epileptic foci with EIT in an

acute animal preparation. It has clear spatial and temporal definition of the foci, and the epileptic discharges are quick to induce and are repeatable in a single animal.