EPILEPSY
An epileptic seizure is a convulsion or transient abnormal event experienced by the subject due to a paroxysmal discharge of cerebral neurones. Epilepsy, by definition, is the continuing tendency to have such seizures, even if a long interval separates attacks. A generalized convulsion or grand mal fit is the commonest recognized event.
INCIDENCE
Epilepsy is a common condition. Some 3% of the population have two or more seizures during their lives. In Britain approximately 65 people suffer from their first seizure each day. Around one-quarter of a million people in Britain take anticonvulsants. In Asia the prevalence is similar to that in Western nations; the condition is said to be over twice as common in Africa.
PATHOPHYSIOLOGY
The spread of electrical activity between cortical neurones is normally restricted. Synchronous discharge of neurones in normal brain takes place in small groups only; these limited discharges are responsible for the normal rhythms of the EEG.
During a seizure, large groups of neurones are activated repetitively and ‘hypersynchronously’, There is a failure of inhibitory synaptic contact between neurones. This causes high-voltage spike-and-wave activity on the EEG. Epileptic activity confined to one area of the cortex is associated with specific symptoms and signs (partial seizures). This activity may remain focal or may spread to cause paroxysmal activity in both hemispheres and a generalized convulsion. This spread is called secondary generalization of a partial seizure.
Seizure threshold
Each individual has a threshold for seizure acnvity.Experimentally some chemicals (e.g. pentylenetetrazol, a gas) induce seizures in all subjects. Individuals who are more likely than others in the population to have seizures in response to various stimuli, for example flashing lights, are said to have a ‘low seizure threshold’, although this is a concept, not an actual measurement.
CLASSIFICATION
Epilepsy is classified according to the clinical type of seizure.
Generalized seizures
Generalized implies abnormal electrical activity which is widespread in the brain, and is primarily of constitutional origin, i.e. developmental.
TONIC-CLONIC SEIZURES (GRAND MAL SEIZURES, GENERALIZED CONVULSIONS). Following a vague warning, the body enters a rigid tonic phase that lasts for up to a minute. Subjects may utter a cry and fall, sometimes injuring themselves. The tongue may be bitten and there may be incontinence of urine or faeces. This is followed by a convulsion (the clonic phase) in which the muscles jerk rhythmically. This lasts a few seconds to a few minutes. Seizures are usually selflimiting, leaving the patient drowsy or in coma for several hour .
TYPICAL ABSENCES (PETIT MAL). This type of generalized epilepsy is almost invariably a disorder of childhood, and by definition an attack is accompanied by 3- Hz spike-and-wave in the EEG. The child ceases activity, stares and pales slightly. The eyelids may twitch. The attack lasts for a few seconds only. A few jerks may occur. After an attack, the child carries on as if nothing had happened. Tpical absence attacks are never due to identifiablelocal lesions. Children with typical absence attacks may in adult life develop generalized seizures.The term petit mal should not be used to describe the absence attacks of partial seizures.
Generalized seizures
1 Absence seizures”
(a) Typical absences with 3-Hz spike-and-wave discharge (petit maf)
(b) Atypical absences with other EEG changes 2 Myoclonic seizures
3 Tonic-clonic seizures (grand mal, majorconvulsions)”
4 Tonic seizures
5 Akinetic seizures
Partial seizures
These start by activation of a group of neurones in one part of one hemisphere. They are also called focal seizures
Simple partial seizures (no impairment of onsciousness): e.g. Jacksonian seizures
2 Complex partial seizures (with impairment of consciousness)”
3 Partial seizures evolving to tonic-clonic seizurs”
4 Apparent generalized tonic-clonic seizures, with EEG but not clinical evidence of focal onset”
Partial seizures (focal seizures)
‘Partial’ or ‘focal’ implies an area of brain, e.g. a temporallobe, which generates abnormal electrical activity that may spread. An acquired lesion, e.g. a tumour, is a cause of such activity. The seizure frequently has clinical features that provide evidence of its site of origin. When these features precede a grand mal fit, the warning they give to the patient or relatives is called the ‘aura’ and the seizure is said to become secondarily generalized. JACKSONIAN (MOTOR SEIZURES). These simple partial seizures originate in the motor cortex. Jerking movements typically begin at the angle of the mouth or in the thumb and index finger, spreading to involve the limbs on the side opposite the epileptic focus. The clinical evidence f
this spread of activity is called the ‘march’ of the seizure. Conjugate gaze (see p.885) may deviate away from a frontal lobe focus (an ‘adversive seizure’). Paralysis of the affected limbs may follow for several hours (Todd’s paralysis) .
TEMPORAL LOBE SEIZURES. These complex partial seizures are associated with strange disturbances of smell or feelings of unreality (jamais vu) or undue familiarity (deja vu) with the surroundings. Visual hallucinations (visions or faces) may be seen. Absence attacks or vertigo may occur.Many other types of partial seizure are known, e.g. autonomic disturbances with piloerection or flushing,sensory disturbances (parietal cortex), crude visual shapes (occipital cortex) or strange sounds (auditory cortex).
AETIOLOGICAL AND PRECIPITATING FACTORS
A cause for epilepsy is found in under one-quarter of patients. A number of secondary factors may trigger seizures in those with a low seizure threshold.
Family history
About 30% of patients with epilepsy have a history ofseizures in first-degree relatives. Usually the mode of inheritance is uncertain; a low seizure threshold appears to run in some families. Generalized typical absence seizures (petit malt are sometimes inherited as an autosomal dominant trait with variable penetrance .
Trauma and surgery
Perinatal trauma (causing cerebral contusion andhaemorrhage) and fetal anoxia are common causes of seizures in childhood. Hypoxic damage to the medial temporal lobes (medial temporal sclerosis) is another cause.
Head injury is sometimes followed by epilepsy within the first week (,early’ epilepsy) or many months or years later (‘late’ epilepsy). To cause epilepsy, the injury must (almost always) be sufficient to cause coma. The presence of early epilepsy, a depressed skull fracture, cerebral contusion, a dural tear or intracranial haematoma increases the incidence of late post-traumatic epilepsy.
Surgery to the cerebral hemispheres is followed by seizures in about 10% of patients.
Pyrexia
High fevers in children under 5 years are sometimes associated with generalized seizures (,febrile convulsions’). In the majority there is no tendency for the seizures to recur in adult life.
Intracranial mass lesions
All mass lesions affecting the cerebral cortex may cause epilepsy-either partial or secondary generalized seizures. f the onset of seizures is in adult life, the chance of an unsuspected mass lesion being present is around 3%.
Family history
Trauma and surgery to the head
Pyrexia in children
Intracranial mass lesions
Cerebral infarction
Drugs, alcohol and drug withdrawal
Encephalitis
Metabolic abnormalities
Degenerative brain disorders
Photosensitivity and auditory stimuli
Hydrocephalus, of any cause, may be associated with seizures.
Cerebral infarction Seizures may follow cerebral infarction, especially in the elderly.
Drugs, alcohol and drug withdrawal
Phenothiazines, monoamine oxidase inhibitors, tricyclicantidepressants, amphetamines, lignocaine and nalidixic acid may occasionally provoke fits either in overdose or in theraputic doses in individuals with a low seizure threshold.
Chronic alcohol abuse is a common cause of seizures.
These occur either while drinking or during periods of abstention. Alcohol-induced hypoglycaemia can also provoke attacks.
Withdrawal of anticonvulsant drugs (especially phenobarbitone) and withdrawal of benzodiazepines may provoke seizures.
Encephalitis and other inflammatory conditions of the brain
Seizures are frequently the presenting feature of encephalitis, chronic meningitis (e.g. tuberculosis), cerebral abscess, cortical venous thrombosis and neurosyphilis. Metabolic abnormalities Seizures may occur with the following metabolic abnormalities:
• Hypocalcaemia
• Hypoglycaemia
• Hyponatraemia
• Acute hypoxia
• Porphyria
• Uraemia
• Hepatic failure
Degenerative brain disorders
Seizures can occur in Alzheimer’s disease and in many rarer degenerative diseases. Epilepsy is three times more common in patients with MS than in the general population.
Photosensitive and other types of reflex epilepsy eizures are sometimes precipitated by flashing lights or a flickering television screen. This photosensitivity can be seen on the occipital recording of the EEG. Very rarely other stimuli provoke attacks.
DIAGNOSIS AND INVESTIGATION
The history from a witness of the attack is of prime importance.
Electroencephalogram
This is the single most useful test in the diagnosis of
epilepsy.
DURING A SEIZURE the EEG is almost invariably abnormal, because epileptic activity reaches the surface of the brain.
EEG EVIDENCE OF SEIZURE ACTIVITY is shown typically by a cortical spike focus (e.g. in a temporal lobe) or by generalized spike-and-wave activity. IN PETIT MAL, 3-Hz spike-and-wave activity is seen. It is always present during an attack and is frequently seen in the interictal intervals (i.e. between attacks). A NORMAL EEG BETWEEN ATTACKS does not exclude epilepsy. Many people suffering from epilepsy have normal interictal EEG activity. In addition, an abnormal interictal EEG does not prove that an attack was epileptic.
EEG TELEMETRY, with video recordings of attacks hasgreatly added to the value of this investigation in the study of attacks of disturbed consciousness whose nature is uncertain.
CT scanning and/or MRI This should be performed on all patients other than children even though the diagnostic yield of treatable lesions is extremely low for both EEG or imaging tests. Other investigations Routine investigations (blood picture, serum biochemistry, chest X-ray) may indicate an underlying metabolic or structural cause. Such tests are normal in idiopathic epilepsy.
TREATMENT
Emergency measures
The emergency treatment of a seizure is simply to ensure that patients harm themselves as little as possible and that the airway is patent in a prolonged seizure and in postictal coma. Wooden mouth gags, tongue forceps and physical restraint frequently cause injury rather than prevent it.
Most seizures last only minutes. A prolonged seizure (longer than 3 min) or repeat seizures outside hospital are best treated with rectal diazepam solution (10 mg). If there is any suspicion of hypoglycaemia, blood should be taken for the measurement of glucose, and intravenous glucose should be given.
Long-term anticonvulsant drugs Anticonvulsant drugs are indicated in recurrent seizures. Opinions differ as to whether treatment is necessary following the first attack. Phenytoin, carbamazepine and sodium valproate are the most effective drugs prescribed. Phenobarbitone, primidone and the benzodiazepine clonazepam are also used. There are differences in opinionabout the most appropriate drugs for each particular variety of seizure: one suggested scheme is given in Table 18.33.
Phenytoin has the advantage of being cheap and effective. The therapeutic level of phenytoin in serum is well defined and this should be monitored in the majority of patients (Table 18.34). The therapeutic serum levels of other anticonvulsants are less clearly defined and routine
estimations are not usually performed. It is preferable to try to use one drug alone in the treatment of epilepsy, although a second (or third) drug may be needed in resistant cases. Alternatively, vigabatrin and lamotrigine can also be used in resistant cases.
UNWANTED EFFECTS. Intoxication with all anticonvulsants causes a syndrome of ataxia, nystagmus and
dysarthria. Chronic administration of phenytoin can cause gum hypertrophy, hypertrichosis, osteomalacia, folatedeficiency, polyneuropathy and encephalopathy. The more common idiosyncratic (i.e. non-dose-related) sideeffects are summarized.
The question of withdrawal of drug therapy is often raised by the patients. Unfortunately, withdrawal can be socially disastrous for patients in preventing them from driving. Careful discussion with an experienced physician is important: withdrawal should not be considered until the patient has been free of all fits for at least 2 years.
Status epilepticus
This is when seizures follow each other without recoveryof consciousness. It is a medical emergency with a mortality of 10-15%. When grand mal seizures follow one another there is a serious risk of death from cardiorespiratory failure. Several treatment regimes are available. Immediate intravenous injection of diazepam 10 mg followed by intravenous infusion of 200 mg lite-lover 24 hours is the first line of treatment. Chlormethiazole 0.8% should be given by intravenous infusion if status epilepticus continues or returns. Phenytoin i.v., phenobarbitone i.v., clonazepam i.v. are also used. Ventilatory support must be available when status is treated.
‘Status’ can also occur in absence seizures and in focal epilepsy. ‘Epilepsy partialis continua’ is a continuous seizure of a small part of the body, e.g. a finger, without loss of consciousness. It is often due to a cortical neoplasm or, in the elderly, a cortical infarct.
Neurosurgical treatment
Several surgical approaches have been used in epilepsy. The most important is amputation of the anterior temporal lobe (usually of the non-dominant side) in those with partial seizures or partial seizures that are secondarily generalized. Indications include poor control on drug therapy and a clearly defined focus of abnormal
lectrical activity.
Pregnancy and epilepsy
Fits are sometimes more frequent mainly because of poorabsorption and poor compliance with drug therapy. Regular monitoring of drug levels is required. Breast feeding is only contraindicated with patients on phenobarbitone or primidone. There is a small increased risk of fetal abnormalities. Higher doses of the contraceptive pill may be required in those taking enzyme-inducing drugs such as phenytoin.
The social consequences of epilepsyThe great majority of patients with epilepsy can be managed by a general practitioner or as an outpatient, and have infrequent seizures that alter the pattern of their lives relatively little. In the small minority who have exceedingly frequent seizures, treatment in hospital or residential care is necessary.
There remains, however, a considerable social stigma attached to the diagnosis, an important fact to be considered when the nature of attacks of disturbed consciousness is uncertain. Employers are reluctant to take on patients who have seizures.
Present trends are to encourage both adults and children with epilepsy to lead lives as unrestricted as possible, though with simple, sensible provisos such as avoiding swimming alone and dangerous sports such as rockclimbing or solo canoeing. It is also wise to advise on simple domestic matters, e.g. that the bathroom door should remain unlocked.
Driving and epilepsy
Those who have suffered from more than one seizure are unable to hold a driving licence in the UK unless they satisfy the following criteria whether on or off treatment. 1 They shall have been free from any form of epileptic attack whilst awake for a period of 2 years prior to the issue of a licence.
2 In the cases of a tacks whilst asleep, the attacks musthave occurred only whilst asleep and the patient must not have had an attack for 3 years prior to the issue of a licence.
The rules for those holding Public SerVice Vehicle and Heavy Goods Vehicle licences (PSV and HGV) are stricter: any attack after the age of 3 years automatically bars an applicant indefinitely from holding such a licence. It is the duty of a doctor to inform patients of these
regulations: the patient should then write to the licensingauthorities. Similar strict regulations exist for potential aircraft plots, sea captains and other similar activities.
The correct diagnosis of an attack at any age has therefore become of major social and legal importance.
