Turner, 978-0-7234-3469-6 99 16 B978-0-7234-3469-6.00016-7, 00016 00016 Epilepsy DEFINITIONS Seizures result from abnormal, paroxysmal, syn- chronous and rapid electrical discharges arising from cerebral neurons. These discharges are usually self-terminating but have a tendency to recur. Epileptic seizure: can be defined clinically as an intermittent, stereotyped disturbance of consciousness, behaviour, emotion, motor function, or sensation, arising from abnormal neuronal discharges. Epilepsy: the condition in which seizures recur, usually spontaneously. Status epilepticus: a state of continued or recurrent seizures, with failure to regain consciousness between seizures over 30 minutes. This is a medical emergency and has a mortality rate of 10–15%. Prodrome: premonitory changes in mood or behaviour; these may precede the attack by some hours. Aura: the subjective sensation or phenomenon that may precede and mark the onset of the epileptic seizure. It may localize the seizure origin within the brain. Ictus: the attack or seizure itself. Postictal period: the time after the ictus during which the patient may be drowsy, confused, and disorientated. The patient may also have residual focal neurological signs, e.g. Todd’s paralysis. • • • • • • • CLASSIFICATION The International Classification of Epileptic Seizures (ICES) was proposed in 1981 to replace older clas- sifications (Fig. 16.1). EPIDEMIOLOGY Between 3 and 5% of the population suffer one or two seizures during their lives. Recurrent seizures occur in 0.5% of the population and 90% of these cases are well controlled with drugs and have pro- longed remissions. Epilepsy more commonly presents during child- hood or adolescence, but can occur at any age. Incidence rates vary with age, being between 20 and 70 cases per 100 000 persons a year; the prevalence rate ranges between 4 and 10 per 1000. There are two peaks in the incidence of grand mal seizures. The first occurs in children and adolescents, in whom no cause can be found. The second occurs in patients in their fifties and sixties, in whom the disease is prob- ably caused by subcortical ischaemic changes second- ary to hypertension. AETIOLOGY Epilepsy is a symptom of numerous disorders but in over 50% of patients with epilepsy, no apparent cause is found, in spite of full investigation. Describe the main types of seizure Describe the aetiological factors associated with epilepsy Understand which drugs are used in the common epilepsy syndromes and their side-effects How would you manage status epilepticus? Understand the social implications of being diagnosed with epilepsy • • • • • Objectives
Transcript
Turner, 978-0-7234-3469-6
99
16B978-0-7234-3469-6.00016-7, 00016
00016 Epilepsy
DEFINITIONS
Seizures result from abnormal, paroxysmal, syn-chronous and rapid electrical discharges arising from cerebral neurons. These discharges are usually self-terminating but have a tendency to recur.
Epileptic seizure: can be defined clinically as an intermittent, stereotyped disturbance of consciousness, behaviour, emotion, motor function, or sensation, arising from abnormal neuronal discharges. Epilepsy: the condition in which seizures recur, usually spontaneously. Status epilepticus: a state of continued or recurrent seizures, with failure to regain consciousness between seizures over 30 minutes. This is a medical emergency and has a mortality rate of 10–15%. Prodrome: premonitory changes in mood or behaviour; these may precede the attack by some hours. Aura: the subjective sensation or phenomenon that may precede and mark the onset of the epileptic seizure. It may localize the seizure origin within the brain. Ictus: the attack or seizure itself. Postictal period: the time after the ictus during which the patient may be drowsy, confused, and disorientated. The patient may also have residual focal neurological signs, e.g. Todd’s paralysis.
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CLASSIFICATION
The International Classification of Epileptic Seizures (ICES) was proposed in 1981 to replace older clas-sifications ( Fig. 16.1 ).
EPIDEMIOLOGY
Between 3 and 5% of the population suffer one or two seizures during their lives. Recurrent seizures occur in 0.5% of the population and 90% of these cases are well controlled with drugs and have pro-longed remissions.
Epilepsy more commonly presents during child-hood or adolescence, but can occur at any age. Incidence rates vary with age, being between 20 and 70 cases per 100 000 persons a year; the prevalence rate ranges between 4 and 10 per 1000. There are two peaks in the incidence of grand mal seizures. The first occurs in children and adolescents, in whom no cause can be found. The second occurs in patients in their fifties and sixties, in whom the disease is prob-ably caused by subcortical ischaemic changes second-ary to hypertension.
AETIOLOGY
Epilepsy is a symptom of numerous disorders but in over 50% of patients with epilepsy, no apparent cause is found, in spite of full investigation.
Describe the main types of seizure Describe the aetiological factors associated with epilepsy Understand which drugs are used in the common epilepsy syndromes and their side-effects How would you manage status epilepticus? Understand the social implications of being diagnosed with epilepsy
Of the symptomatic causes in adults, vascular disease (especially stroke), alcohol abuse, cerebral tumours, and head injury are the most common.
Factors that may predispose to seizures are described below.
Family history There is an increased liability to seizures in relatives of patients with epilepsy. This is especially true in the case of absence seizures, where up to 40% of cases have a family history. No single genetic trait can account for the vast heterogeneity of all epileptic syn-dromes. The mechanism probably involves factors that alter membrane structure or function, which may lead to a lowered seizure threshold.
Prenatal and perinatal factors Intrauterine infections such as rubella and toxo-plasmosis, as well as maternal drug abuse and irra-diation in early gestation, can produce brain damage and neonatal seizures. Perinatal trauma and anoxia, when sufficiently severe to cause brain injury, may also result in epilepsy.
Trauma and surgery Severe closed or open head trauma is often fol-lowed by seizures. These can be within the first week (‘early’), or may be delayed up to several months or years (‘late’), when the likelihood of chronic epilepsy is greater. Surgery to the cerebral hemispheres is followed by seizures in about 10% of patients.
Metabolic causes Many electrolyte disturbances can cause neuronal irritability and seizures such as hyponatraemia and hypernatraemia, hypocalcaemia, hypomagnesaemia, and hypoglycaemia. Other metabolic causes include uraemia, hepatic failure, acute hypoxia, and porphy-ria. Chronic metabolic encephalopathies can produce permanent grey-matter injury.
Toxic causes Drugs such as phenothiazines, monoamine oxidase inhibitors, tricyclic antidepressants, amphetamines, lidocaine, and nalidixic acid may provoke fits, either in overdose or at therapeutic levels in patients with a lowered seizure threshold.
Withdrawal of antiepileptic medication and ben-zodiazepines may also cause seizures especially when it is done rapidly.
Chronic alcohol abuse is a very common cause of seizures. These may occur while drinking, during a with-drawal phase, secondary to hypoglycaemia or trauma.
Other toxic agents capable of causing seizures include carbon monoxide, lead, and mercury.
Infectious and inflammatory causes Seizures may be the presenting feature or part of the course of encephalitis, meningitis, cerebral abscess, or neurosyphilis, and usually indicate a poorer prog-nosis in these conditions. High fevers secondary to non-cerebral infections in children over 6 months and under 6 years of age are a common cause of gen-eralized seizures (‘febrile convulsion’). These are usu-ally self-limiting, and seizures do not tend to recur in adult life.
Vascular causes Up to 15% of patients with cerebrovascular disease experience seizures, especially with large areas of
Fig. 16.1 International classification of epileptic seizures
Partial seizures (seizures beginning focally)
− Simple (consciousness not impaired) With motor symptoms With somatosensory or special sensory symptoms e.g. taste/smell. With autonomic symptoms With psychological, e.g. 'jamais vu' or 'deja vu' symptoms
− Complex (with impairment of consciousness) Beginning as a simple partial seizure and progressing to a complex partial seizure Impairment of consciousness at onset
infarction or haemorrhage. Less common vascular causes of seizures include cortical venous thrombo-sis and arteritis (e.g. polyarteritis nodosa) as well as vascular malformations.
Intracranial tumours Sudden onset of seizures in adult life, especially if partial, should always raise the possibility of an intracranial tumour.
Hypoxia Seizures can develop during or following respiratory or cardiac arrest secondary to anoxic encephalopathy.
Degenerative diseases All patients with degenerative corticoneuronal dis-eases of the brain have an increased risk of seizures (e.g. Alzheimer’s disease).
Photosensitivity Some seizure types are precipitated by flashing lights, or flickering television or computer screens.
Sleep deprivation Sleep deprivation often precipitates seizures in sus-ceptible patients.
PATHOPHYSIOLOGY
Electrical discharges between neurons are usually restricted, and produce the normal rhythms recorded on the electroencephalogram (EEG).
When a seizure occurs, large groups of neurons are activated repetitively and ‘hypersynchronously’, with dysfunction of the inhibitory synaptic con-tact between neurons. This produces the high-volt-age spike-and-wave activity on the EEG typical of a seizure.
The onset of the epileptic discharge may include the whole cortex (‘primary generalized’), may be con-fined to one area of the cortex (‘partial’), or may start focally and then spread to involve the whole cortex (‘secondary generalization of a partial seizure’).
CLINICAL FEATURES
The diagnosis of epilepsy is primarily a clinical one. A detailed history is therefore essential and usually requires eyewitness reports, particularly when con-sciousness is lost during the event.
If an aura preceded the attack, the patient may be able to describe this, which may help localize the focus. The aura may not be rememebered by the patient especially if there is secondary generaliza-tion.
Simple partial seizures Simple partial seizures involve focal symptoms. Motor and sensory seizures, arise in the frontal motor or parietal sensory cortex and affect the con-tralateral face, trunk, or limbs. Simple partial sei-zures can occur in any region of the cerebral cortex,e.g. bad tastes or smells, jamais vu / deja vu with tem-poral lobes seizures or abnormal behaviour in fron-tal seizures. There is no loss of consciousness unless there is a subsequent spread of activity (‘secondary generalization’). A structural brain lesion must be excluded (e.g. stroke, tumour, or abscess).
Complex partial seizures Complex partial seizures usually originate in the temporal or frontal lobe and cause a disturbance of consciousness usually without loss of postural con-trol, i.e. the patient remains standing. The actual attack varies between and within individuals. In tem-poral lobe complex partial seizures the patient may experience déjà vu , depersonalization, epigastric full-ness, strange tastes or smells, fidgeting with fingers and lip smacking (limb and oral automatisms), and altered emotion. Typically, witnesses suggest that the
Failure to comply with medication is a very common cause of seizures, including status epilepticus. Usually, the patient fails to comply because of side-effects of the anti-convulsants or difficulty coming to terms with their condition psychologically. It is therefore important to ask about troublesome side-effects and discuss alternatives with the patient and the GP.
patient either wanders in a confused state and is only partly responsive or stops what they were doing and stares meaninglessly with repetitive oral and hand movements. Complex partial seizures typically last up to 10 minutes but can continue for several hours as a part of ‘non-convulsive status epilepticus’.
Absence seizures (petit mal) Absence seizures have an onset between 4 and 12 years of age. The attacks may occur several times a day, with a duration of 5–15 seconds. The patient suddenly stares vacantly. There may be eye blinking and myoclonic jerks. They are often diagnosed fol-lowing complaints about an inattentive child with a deteriorating performance at school.
Tonic-clonic seizures (grand mal) Tonic-clonic seizures start with a sudden loss of con-sciousness and fall to the ground. This is followed by the ‘tonic’ phase, which lasts for about 10 seconds, when the body is stiff, the elbows are flexed, and the legs extended. Breathing stops and the patient may turn cyanotic.
The tonic phase is followed by the ‘clonic phase’, which usually lasts for 1–2 minutes, and during which there is violent generalized rhythmical shak-ing. The eyes roll back, the tongue may be bitten, and there is a tachycardia. Bladder and bowel con-trol may be lost. Breathing recommences at the end of this phase. Following a tonic-clonic seizure, the patient often cannot be roused for several minutes and awakes with confusion, headache, myalgia, and some retrograde amnesia.
HISTORY AND INVESTIGATIONS TO AID DIAGNOSIS
The diagnosis of a seizure is based on the clinical history; additional information can be provided by brain imaging, the EEG, or blood tests. The use of neuroimaging is more important in cases with a late onset (over the age of 25 years), that are partial, refractory to treatment, are associated with persisting abnormal clinical signs, or when the presentation is with status epilecticus.
Clinical features during an attack that support the diagnosis of a seizure include pupil dilatation,
raised blood pressure and heart rate, extensor plantar responses, and central and peripheral cyanosis.
In generalized seizures, the pO 2 and pH are low-ered, the creatine phosphokinase (CPK), or creatine kinase (CK) is elevated, and there is a marked elevation of serum prolactin.
The EEG is extremely useful if recorded during an attack and may show spike and wave activity. Interictal EEGs are often normal but may show focal spikes or slow waves suggesting subclinical seizure activity. In some cases, abnormal activity can be provoked by hyperventilation or photic stimulation (flashing light). This is especially true for absence seizures, in which there is the characteristic three-per-second spike-and-wave pattern in all leads.
Computed tomography (CT) or magnetic reso-nance imaging (MRI) may reveal structural lesions that have caused the seizures, especially if there is a partial onset. In complex partial seizures of temporal lobe origin, the MRI may demonstrate hippocampal sclerosis.
It is important to distinguish epilepsy from other causes of transient focal dysfunction or loss of con-sciousness, as there are social and economic implica-tions when a diagnosis of epilepsy is made, e.g. the patient is unable to drive or operate certain machinery.
The most common differentials of a convulsive seizure include:
Syncope (vasovagal attacks, arrhythmias, carotid sinus hypersensitivity, postural hypotension): there is usually prodromal pallor, nausea, and sweating. Palpitations may be experienced with arrhythmias. Non-epileptic seizures or ‘pseudoseizures’: psychologically determined, feigned seizures are surprisingly common, especially in patients with known epilepsy. The following features help to differentiate a pseudoseizure from an epileptic seizure: pupils, blood pressure, heart rate, pO 2 , and pH remain unchanged; plantar responses are flexor; serum prolactin levels are normal; the EEG shows no seizure activity during the episode and no postictal slowing. Transient ischaemic attacks (TIAs): these can include transient loss of consciousness – among other brainstem symptoms – when the posterior circulation is involved but this is very uncommon and often overdiagnosed. Hypoglycaemia: this can cause behavioural disturbance and seizures.
Antiepileptic treatment should be considered when two or more unprovoked seizures have occurred within a short period. Whenever possible, treatment should involve only one drug, to avoid interaction between the anticonvulsants and additive side-effects. Treatment is aimed at making the patient seizure free, but this is not always possible.
The most common anticonvulsants in current clinical use are carbamazepine, sodium valproate, lamotrigine, and phenytoin. Second-line drugs include gabapentin, topiramate, levetiracetam, and phenobarbitone. In general, the first-line drugs for primary generalized epilepsy in adults are sodium valproate or lamotrigine, for absence epilepsy in children is ethosuximide or sodium valproate, and for partial seizures is carbamazepine or lamotrigine. Many patients still take phenobarbitone and pheny-toin for generalized seizures but these are less com-monly prescribed because of their side-effect profile. Some patients may still be taking vigabatrin but this is used rarely now because it can cause progressive and irreversible visual field defects.
Whichever drug is used, the dose should be built up slowly. Measurement of blood drug concentra-tions is important for phenytoin, as it displays zero-order kinetics and small increases in dose can cause it to reach toxic levels. For other drugs, therapeutic drug monitoring, if available, can be used to check compli-ance or to confirm clinically diagnosed toxicity. If the patient is seizure and side-effect-free and has a slightly high serum anticonvulsant level then it is usually more appropriate not to change the drug dosage. Phenobarbitone is still used in refractory epilepsy and status epilepticus and levels should be monitored.
Pharmacokinetics of antiepileptic drugs Phenytoin, phenobarbitone, topiramate and car-bamazepine are well known to induce enzymes within the liver that metabolize other drugs. This effect is most important when using several antiepi-leptic drugs together and when the patient is on the combined oral contraceptive pill. Many of the antie-pileptic drugs also block pathways within the liver for metabolism of drugs, e.g. sodium valproate prolongs the half-life of lamotrigine. Care must be taken when
prescribing these drugs, especially in combination, to avoid toxic levels and other adverse reactions.
Adverse effects of antiepileptic drugs All antiepileptic drugs can produce acute, dose-related, idiosyncratic or chronic toxicity, and variable degrees of teratogenicity (damage to the developing fetus).
Acute toxicity All anticonvulsants can cause drowsiness and slowed cognition especially at higher doses. Some antiepileptic drugs cause a non-specific encephalopathy when blood levels are high. This is associated with sedation, nystag-mus, ataxia, dysarthria, and confusion. If any of these features is present, blood levels must be measured.
Idiosyncratic toxicity Allergic skin reactions occur in up to 10% of patients on phenytoin and in up to 15% on carbamazepine. Lamotrigine can be associated with a particularly severe skin rash. These can be reduced by introduc-ing these drugs slowly, at low doses, and building up to therapeutic levels. Bone marrow aplasia is a rare idiosyncratic complication of carbamazepine.
Chronic toxicity Chronic toxicity is especially associated with pheny-toin and includes the development of coarsened facies, acne, hirsuitism, gum hypertrophy, and pos-sibly peripheral neuropathy. All anticonvulsants appear to have some effect on cognitive function and can cause drowsiness. This is especially a prob-lem with phenytoin. Carbamazepine and phenytoin can cause a sometimes-irreversible cerebellar ataxia in a dose-related manner. Generally, carbamazepine and sodium valproate have fewer chronic effects than phenytoin. Lamotrigine is being increasingly used for many types of epilepsy because of its low side-effect profile, to date, including low levels of teratogenic-ity. Levetiracetam is also being used more frequently because of a relatively lower incidence of side-effects and absence of effect on hepatic metabolism.
Teratogenicity Phenytoin increases the risk of major fetal malforma-tion including hair lip, cleft palate, and cardiovascular
anomalies by a factor of two to three times. The use of sodium valproate and carbamazepine in preg-nancy is associated with neural tube defects. Folate supplements and early screening using ultrasound and amniocentesis (to test for alpha-fetoprotein) are indicated in such cases.
Patients with epilepsy and on treatment who wish to become pregnant should seek specialist advice before conception and require regular follow-up by a neurologist during the pregnancy.
Withdrawal of antiepileptic drugs In view of the many adverse reactions associated with anticonvulsants, a patient who has achieved remis-sion for over 2 years should be considered for drug withdrawal. However, there is the risk of recurrence of seizures, especially in some forms of epilepsy, and this has important consequences for driving, employ-ment, and self-esteem. Thus, the final decision to attempt withdrawal must be made by the patient and, if undertaken, must be carried out very slowly, with gradually decreasing doses.
STATUS EPILEPTICUS
‘Serial epilepsy’ is defined as a succession of tonic-clonic seizures without regaining of consciousness between attacks. The patient has ‘status epilepticus’ when the seziures continue for greater than 30 min-utes without stopping. If left untreated, this can lead to irreversible brain damage as the patient becomes hypoxic and eventually death ensues.
Patients with status epilepticus require immedi-ate resuscitation. This involves establishing an airway and administering oxygen. The circulation should be assessed and an infusion set up with normal saline.
Blood tests comprise blood gases, glucose, elec-trolytes, renal and liver function, and anticonvulsant levels.
Drug treatment It is helpful to plan therapy in a series of progressive phases:
Premonitory stage (0–10 minutes): rapid treatment may prevent the evolution to status. Lorazepam, diazepam, midazolam, or paraldehyde can be used at this stage. Early status (10–30 minutes): a dose of fast-acting intravenous benzodiazepines such as lorazepam. This can be repeated once if seizures are not terminated. Repeated doses of benzodiazepines may lead to an accumulation and an increased risk of respiratory depression especially with diazepam. Established status (30–60 minutes): phenobarbitone or phenytoin is usually given at this stage with intravenous loading doses. Refractory status (after 60 minutes): by this stage, anaesthesia is required, with ventilation and intensive care treatment. The most common agents used are intravenous thiopentone or propofol. EEG monitoring is very helpful to confirm when status has been aborted. In all cases, neuromuscular blockade should be avoided if possible, because if the seizures return, the patient’s muscles will be paralysed and therefore the return of seizure activity may go unnoticed.
Despite the best medical management, there is still 5–10% mortality with status epilepticus, especially when the cause is due to a catastrophic intracerebral event.
NEUROSURGICAL TREATMENT OF EPILEPSY
The indication for surgical treatment requires the accurate identification of a localized site of onset of seizures or the ability to disconnect epilep-togenic zones and prevent spread as a palliative procedure.
The majority of the procedures undertaken in cen-tres worldwide involve some form of temporal lobe surgery. Less commonly, extratemporal cortical exci-sions, hemispherectomies, and corpus callosotomies are carried out.
For temporal lobe surgery, the two conditions with the best surgical outcome are mesial temporal
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If hypoglycaemia is suspected in a patient with a possible history of alcohol abuse or malnutrition then thiamine must be given with intravenous glucose, as glucose alone can precipitate Wernicke’s encephalopathy.
sclerosis (Ammon’s horn sclerosis) or an indolent glioma of the medial temporal region. Development anomalies such as dysembryoplastic neuroepithelial tumours (DNET) are increasingly being diagnosed as the cause of partial epilepsy and some are amenable to surgical removal.
THE SOCIAL CONSEQUENCES OF EPILEPSY
Considerable social stigma is often attached to a diag-nosis of epilepsy. There are implications for employ-ment, not only in the ability to carry out certain jobs (e.g. driving or using machinery) but also because many employers are unwilling to take on people with epilepsy.
The aim is to allow patients to lead as unrestricted a life as possible but bearing in mind some precau-tions, such as to avoid swimming alone or engag-ing in dangerous sports such as rock climbing. They should also be advised about simple domestic precautions such as not locking the bathroom door.
DRIVING AND EPILEPSY
The DVLA can revoke a British driving licence in any individual felt to be unsafe to himself/herself and/or the public. Patients who have had one or more sei-zures need to contact the DVLA regarding the length of period they are not allowed to drive. As a guide, the following conditions need to apply before the patient can return to driving with or without treatment:
Patients cannot drive for 1 year after a single seizure. Patients who have only nocturnal seizures may drive if they are seizure free during the daytime for 3 years. For single seizures with a specific provocative cause that is unlikely to recur, e.g. encephalitis or acute drug toxicity, the ban on driving may be for only 3–6 months. Patients who are driving and taking antiepileptic drugs but who wish to stop epileptic medication are recommended to stop driving during cessation and for 6 months following the last dose of their drug.
