Chapter 2. Review of the literature

Table of Contents
2.1. General aspects of epilepsy
2.2. Temporal lobe epilepsy
2.3. Treatment of epilepsy
2.4. Autonomic nervous system
2.5. Evaluation of autonomic nervous system function
2.6. Epilepsy and autonomic nervous system

2.1. General aspects of epilepsy

2.1.1. Definition

Epilepsy is characterised by recurrent, unprovoked, paroxysmal episodes of brain dysfunction manifesting as a large number of clinical phenomena, like altered levels of consciousness, involuntary movements, abnormal sensory phenomena, autonomic changes and transient disturbances of behaviour. It is a variety of symptoms arising from different kinds of pathologic processes of the brain rather than a specific disease or even a syndrome. During epileptic seizures, there are excessive discharges of electrical activity of the neurones in the brain, and the clinical manifestations depend on the origin and the localization of those pathological discharges. (Browne & Feldman 1983, Waltimo 1983, Engel & Pedley 1997)

2.1.2. Epidemiology

The incidence of epilepsy is 24-53/100 000 person-years in Western countries, whereas in the developing countries it is thought to be higher. The incidence range is higher during the first years of life, falls dramatically thereafter, and increases again in the elderly. Approximately 50% of cases of epilepsy begin in childhood or adolescence (Hauser et al 1993). Many studies suggest that males are at a greater risk for unprovoked seizures and epilepsy than female subjects (Hauser 1997). The prevalance of epilepsy is 0,7-0,8% worldwide and the lifetime cumulative incidence is 1-3%. According to the Finnish Social Insurance Institution more than 45 000 patients received antiepileptic medication in Finland in 1996, and 5000 - 6000 of them were children (Keränen et al 1997). Seizure-specific incidence or proportions of cases with specific seizure type based on the International Classification of Epileptic Seizures are provided in several contemporary incidence studies (Hauser 1997). Keränen and his colleagues studied the distribution of seizure types in an epidemiogical study of 1220 patients over 15 years of age in Finland (Keränen et al. 1988). The epilepsy type was unclassified in 17.5% of the cases. The subclassification of the 82.5% of the cases revealed partial seizures in 56% of the patients and generalized seizures in 26.5% of the patients (Table 1).

Table 1. Distribution of seizure types in an epileptic population in Kuopio, Finland (Keränen et al. 1988).

Epilepsy typeProportion of cases of epilepsy
Partial seizure56.0%
Simple partial7.5%
Complex partial23.0%
Partial seizure with secondary generalization25.5%
Generalized seizures26.5%
Absence seizures1.0%
Atypical absence seizures0.5%
Tonic-clonic23.0%
Atonic0.7%
Myoclonic1.3%
Unclassified17.5%
Total100%

2.1.3. Etiology

The most common etiologic factors of epilepsy according to the Rochester study are presented in Table 2 (Hauser 1997). All factors that can affect the brain, i.e. head traumas, neoplasms, degenerative diseases, infections, metabolic diseases, ischaemia and hemorrhages, can predispose a person to epilepsy (Vinters et al 1993). At present, more and more genetic factors underlying different types of epileptic syndromes are revealed. It is also known that certain brain areas, i.e. temporal and frontal lobes, are more susceptible to produce epileptic seizure activity than the others (Larsen & Iivanainen 1994). However, there are also patients with unresolved etiology of epilepsy (Hauser 1997).

Table 2. Proportion of incidence cases of epilepsy by etiology, Rochester, Minnesota, 1935-1984 (Hauser 1997).

Etiology of epilepsyProportion of incidence cases
Idiopathic/cryptogenic65.5%
Vascular10.9%
Congenital8.0%
Trauma5.5%
Neoplastic4.1%
Degenerative3,5%
Infection2.5%
Total100%

2.1.4. Classification

A summary of International Classification of Epilepsies and Epileptic Syndromes is presented in Table 3. If there is a known etiology for epilepsy, it is called symptomatic. In cryptogenic epilepsy the presumed pathologic process of the brain can not be detected by the methods in use. Idiopathic epilepsies are more common in children than in adults and comprise a variety of childhood epileptic syndromes with an unknown etiology. (Commission on Classification and Terminology of the International League Against Epilepsy 1989)

Seizures are categorized as partial or generalized and are discussed shortly in the next chapters.

Table 3. International classification of epilepsies and epileptic syndromes (Commission on Classification and Terminology (ILAE, 1989).

ClassClassification
1.Localization-related (focal, local, partial)
1.1Idiopathic (with age-related onset)
Benign childhood epilepsy with centrotemporal spikes
Childhood epilepsy with occipital paroxysm
Primary reading epilepsy
1.2Symptomatic
Chronic progressive epilepsia partialis continua of childhood
1.3Crypotgenic
The symtpomatic and cryptogenic categories comprise syndromes of great individual variability that are based on:
Seizure types (according to the International Classification of Epileptic Seizures)
Anatomic localization: Temporal, frontal, parietal, and occipital lobe epilepsies
Bi- and multilobar epilepsies
Etiology (in symptomatic epilepsies)
Spesific modes of precipitation
2Generalized
2.1Idiopathic (with age-related onset, in order of age)Benign neonatal familial convulsionsBenign neonatal convulsionsBenign myoclonic epilepsy of infancyChildhood absence epilepsy (pyknolepsy)Juvenile absence epilepsyJuvenile myoclonus epilepsy (impulsive petit mal)Epilepsy with grand mal (GTC) seizures on awakingOther idiopathic generalized epilepsies not defined aboveEpilepsies with seizure precipitated by specific modes of activation
2.2 Symptomatic
2.3.1Nonspecific etiologyEarly myoclonic encephalopathyEarly infantile epileptic encephalopathy with suppression-burstOther symptomatic generalized epilepsies not defined above
2.3.2Specific syndromes (see the original reference)
3Epilepsies and syndromes undetermined whether focal or generalized
3.1With both generalized and focal seizuresNeonatal seizuresSevere myoclonic epilepsy of infancyEpilepsy with continuous spike-waves during sleepAcquired epileptic aphasia (Landau-Kleffner syndrome)Other undetermined epilepsies not defined above
3.2Without unequivocal generalized or focal features (e.g. many cases of sleep-grand mal)
4.Special syndromes
4.1Situation-related seizures (Gelegenheitsanfälle)Febrile convulsionsIsolated seizures or isolated status epilepticusSeizures due to acute metabolic or toxic factors such as alcohol, drugs, eclampsia

2.1.4.1. Partial seizures

Seizures that begin in a focal region of the cerebral cortex, often within one lobe of the brain are termed partial seizures. Partial seizures may remain focal throughout the duration of the seizure or may propagate via neuronal pathways and networks to various regions of the hemisphere (Chabolla 2002). When partial seizure spreads to involve the majority of both cerebral hemipheres, it is said to be secondary generalized (Chabolla 2002). Partial epilepsies comprise slightly over 50% of all epilepsies (Keränen et al. 1988, Hauser 1997, Williamson et al. 1997).

The signs and symptoms associated with a partial seizure depend on the cortical regions involved. In theory, any function produced by the cortex (e.g. somatosensory, motor, autonomic, psychic phenomena) may be a symptom of a seizure, and the first sign or symptom of a seizure is often, but not always, the best indicator of the site of seizure origin. The most common sites of producing epileptic discharges are temporal and frontal lobes. (Chabolla 2002) TLE is discussed in detail in chapter 2.2.

2.1.4.2. Generalized seizures

When epileptic seizure involves both cerebral hemispheres at the onset, it is termed (primary) generalized. At the onset of a generalized seizure patients may experience a vague, indescribable warning, although the vast majority of patients lose consciousness without premonitory symptom. With the loss of consciousness, tonic-clonic convulsions occur. A generalized seizure may also manifest itself as absence, atonic or myoclonic seizures. Idiopathic generalized epilepsies are often childhood idiopathic syndromes, some of which have an excellent prognosis, whereas some of them (e.g. juvenile myoclonus epilepsy (JME)) are thought to require life long medication. (Chabolla 2002)

2.1.5. Diagnosis

Anyone can have an epileptic seizure under stressful conditions (i.e. sleep deprivation, alcohol or drug abuse, infections, hypoglycemia, metabolic changes). However, the diagnosis of epilepsy can be made only after two unprovoked epileptic seizures.

The procedures needed for the diagnosis of epilepsy include medical history with information on the possible predisposing events, a detailed description of the seizures, and clinical evaluation with special respect paid to the cardiovascular and neurological examination. An EEG-recording is usually obtained, and it may reveal focal or generalized spikes and slow waves or other epileptic phenomena. Magnetic resonance imaging (MRI) is recommended as the first line imaging method of the brain when seizures are thought to be of focal origin. MRI may detect pathologic conditions that can not be diagnosed with CT. It is not unusual, however, that the diagnosis of epilepsy is based on medical history and information on the clinical characteristics of the seizures, and EEG and MRI results are normal. (Moshé & Pedley 1997)

2.1.6. Prognosis

The prognosis of epilepsy depends greatly on the underlying cause. At the beginning of the last century, all epilepsies were considered chronic. Later, however, the prognosis has become markedly better with the better epidemiological studies of less selected populations. The studies indicate that when treated, more than two thirds of the patients with newly diagnosed epilepsy soon enter long-term remission. The meta-analyses of recurrence studies found risk rate for seizure recurrence of 0.25 (95% CI, 0.21 - 0.30) at 1 year after discontinuation of the treatment, and of 0.29 (0.21-0.30) at 2 years. Symptomatic epilepsies are more likely to relapse than idiopathic or cryptogenic epilepsies. An abnormal EEG pattern may also increase the risk for the recurrence of seizures. (Sander & Sillanpää 1997)

On the other hand, it is well known that the mortality of the patients with epilepsy exceeds 2-3 times that among the general population. The increased mortality is due to excess morbidity (various brain diseases), accidents during the seizures, status epilepticus, and suicides. The most important epilepsy-related death is SUDEP that accounts for as much as 10-15 % of the deaths among epilepsy patients. SUDEP is discussed in detail in chapter 2.4.1. Many childhood epilepsies have a better prognosis than epilepsies in adults, but there are also severe childhood epilepsies that may eventually lead to increasing neurological deficits and, even, to death. (Sander & Sillanpää 1997)