Epilepsy/epileptic seizures

Seizure A sudden attack of symptoms usually associated with diseases such as epilepsy. Epileptic seizures are due to the random, uncontrolled firing of a group of cerebral neurons, which results in a variety of sensory and motor manifestations. 

All such animal procedures suffer from the obvious and basic problem that laboratory animals do not behave like humans and that humans cannot reliably interpret their reactions and behaviour. Thus we know that Parkinson s disease is caused by a degeneration of the dopaminergic nigrostriatal tract but its lesion in animals does not produce any condition which resembles human Parkinsonism, except in primates, even though there are functional tests (e.g. rotational movements) which readily establish that loss of dopamine function and also respond to its augmentation (Chapter 15). By contrast, there are many ways, e.g. electrical stimulation and the administration of certain chemicals, to induce convulsions in animals and a number of effective antiepileptic drugs have been introduced as a result of their ability to control such activity. Indeed there are some tests, as well as animals with varied spontaneous seizures, that are even predictive of particular forms of epilepsy. But then convulsions are a very basic form of activity common to most species and epileptic seizures that are characterised by behavioural rather than motor symptoms are more difficult to reproduce in animals. 

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. 

FIGURE 27-1. International League Against Epilepsy classification of epileptic seizures. Data from reference 16. 

Apart from this epileptic seizure classification, an additional classification specifies epileptic syndromes, which refer to a cluster of symptoms frequently occurring together and include seizure type, etiology, age of onset and other factors [2]. The epileptic syndromes have been categorized into partial versus generalized epilepsies. The partial... 

Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 22 489-501,1981. 

Zinc is important to the normal functioning of the central nervous system (CNS). At low concentrations, zinc protects mammalian brain neurons by blocking N-methyl-D-aspartate receptor-mediated toxicity. At high concentrations, zinc is a potent, rapidly acting neurotoxicant in the mammalian brain, as judged by zinc-induced neuronal injury of in vitro mature cortical cell cultures (Choi et al. 1988). Increased brain levels of zinc are associated with Pick s disease in certain strains of rodents with inherited epileptic seizures. Intravenous injection of zinc in rats with genetically inherited epilepsy produces seizures a similar response occurs with intracranial injection of zinc in rabbits with inherited audiogenic seizures (Choi et al. 1988). 

The International Classification of Epileptic Seizures (Table 52-1) classifies epilepsy on the basis of clinical description and electrophysiologic findings. 

Clinically, it was found that for epilepsy patients, the optimal dose for adults is 1.6-2 g/day for children it is 1-1.5 g/day. Under this dosage complete disappearance of epileptic seizures is noted in over 20 per cent of cases [619,625]. 

Epilepsy is a chronic brain disease of diverse etiology it is characterized by recurrent paroxysmal episodes of uncontrolled excitation of brain neurons. Involving larger or smaller parts of the brain, the electrical discharge is evident in the electroencephalogram (EEG) as synchronized rhythmic activity and manifests itself in motor, sensory, psychic, and vegetative (visceral) phenomena Because both the affected brain region and the cause of abnormal excitability may differ, epileptic seizures can take many forms. Erom a pharmaco-therapeutic viewpoint, these may be classified as ... 

Epilepsy For control of grand mal, psychomotor, or focal epileptic seizures, either alone or with other anticonvulsants. It may control grand mal seizures refractory to other anticonvulsants. 

Epilepsy is a chronic often progressive disorder of the central nervous system (CNS). Periodic and unpredictable epileptic seizures caused by the abnormal electrical discharge of neurones in various anatomic structures of the CNS is the characteristic feature. This is an approximate definition based on international classifications of seizures and syndromes which take into account the extremely variable clinical and electroencephalographic expression of the disease. The annual incidence of epilepsy is an estimated 20-70 cases per 100,000 inhabitants with a prevalence of 0.4-0.8%. Globally, incidence is higher during childhood, remaining rather stable... 

Epilepsy (or epilepsies, since markedly different clinical entities exist) is a common neurological abnormality affecting about 1% of the human population. Epilepsy is a chronic, usually life-long disorder characterized by recurrent seizures or convulsions and usually, episodes of unconsciousness and/or amnesia. Table 32.1 illustrates the major types of epileptic seizures. Patients often exhibit more than one type. In most instances, the cause of the seizure disorder is not known (idiopathic epilepsy), although trauma during birth is suspected of being one cause. 

Epilepsy is an example of excessive neural signaling in the central nervous system. Relative cellular and extracellular space (ECS) volume has been demonstrated to play an important role in the propensity for epileptic seizures. For example, reducing ECS volume by exposure to hypotonic medium produces hyperexcitability and enhanced epileptiform activity, whereas hyperosmolar medium reduces excitability. The hypothesis that AQP4-dependent water transport in astrocytes might modulate intrinsic brain excitability was tested by seizure susceptibility in response to the GABAa antagonist convulsant pentylenetetrazol... 

Various religious prophets such as Saint Paul, Ezekiel, and Mohammed may have suffered from epileptic seizures. Recently, several nuns with temporal lobe epilepsy (TLE) have provided evidence that TLE is the root of many mystical religious experiences. For example, one former nun apprehended God in TLE seizures and described the experience ... 

Epilepsy can be caused by genetic factors, brain trauma or injury, viral infections, and likely additional factors that have not yet been discovered. Some people, who may not even be diagnosed with epilepsy, may experience seizures in response to certain patterns of lights and sounds. More severe cases sometimes require the part of the brain that is believed to be the source of the massive storm of electrical signals to be removed surgically. However, epileptic seizures are usually treated with anticonvulsant medications. 

Modeling in the brain is mainly targeted to the general qualitative principles underlying various phenomena such as epileptic seizures [574], and not to quantitative assessment and forecasting as one would expect to achieve in simpler systems. For example, in [479], recurrent inhibition and epilepsy are studied and also penicillin is considered as a q-aminobutyric acid inhibitor. 

Seizures Clonazepam [kloe NA ze pam] is useful in the chronic treatment of epilepsy, whereas diazepam is the drug of choice in terminating grand mal epileptic seizures and status epilepticus (see p. 149). Chlordiazepoxide [klor di az e POX ide], clorazepate [klor AZ e pate], diazepam, and oxazepam [ox A ze pam] are useful in the acute treatment of alcohol withdrawal. 

The adverse effects of most serious concern relate to the cardiovascular system and seizure threshold. Actions on the adrenergic and cholinergic systems probably contribute to both hypotensive and direct cardiac effects, including alterations in heart rate, quinidine-like delays in conduction, and reduced myocardial contractility. The seizure threshold is lowered, increasing the frequency of epileptic seizures. All of these adverse effects can occur at therapeutic dosages in susceptible populations, such as elderly people, children, and people with cardiac problems or epilepsy, but are also a major cause of morbidity and mortality in accidental or intentional overdosage. Doses in excess of 500 mg can be seriously toxic, and death is fairly common when doses of 2 g or more are taken. 

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. 

An epileptic seizure is a transient symptom of abnormal, excessive or synchronous neuronal activity in the brain (normal brain activity is marked by unsynchronised firing of neurons). It can manifest as an alteration in mental state, tonic or clonic movements and convulsions. The medical syndrome of recurrent, unprovoked seizures is termed epilepsy, but seizures can occur in people who do not have epilepsy. 

Partial or generalized epileptic seizures occur for the first time in about 2% of those with acute strokes at around the time of onset, rising to approximately 10% at five years, more with large cortical infarcts or intracranial hemorrhage (Ch. 9) (Ferro and Pinto 2004). Seizures are more common with large strokes, especially if hemorrhagic, and with cortical as opposed to lacunar strokes. Cerebrovascular disease is the most common cause of epilepsy in the elderly, and late-onset epilepsy is a predictor of subsequent stroke (Cleary et al. 2004). Seizures may cause neurological deterioration or be mistaken for recurrent stroke. Intractable recurrent seizures are distinctly unusual. 

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