EPILEPSY
Dr.BASHAR SHAKER
20 -11 - 2019
A seizure can be defined as the occurrence of signs and/or symptoms due to abnormal, excessive or synchronous neuronal activity in the brain.
The lifetime risk of an isolated seizure is about 5%, although incidence is highest at the extremes of age.
Epilepsy is the tendency to have unprovoked seizures.While the prevalence of active epilepsy in European countries is about 0.5%, the figure in developing countries may be higher
A recent change in definition allows the diagnosis of epilepsy to be made after a single seizure with a high risk of recurrence
(e.g. a single seizure in the presence of a cortical lesion).
Pathophysiology
To function normally, the brain must maintain a continual balancebetween excitation and inhibition, remaining responsive to the
environment while avoiding continued unrestrained spontaneous
activity.
The inhibitory transmitter gamma-aminobutyric acid
(GABA) is particularly important, acting on ion channels to enhance
chloride inflow and reducing the chances of action potential
formation. Excitatory amino acids (glutamate and aspartate)
allow influx of sodium and calcium, producing the opposite
effect.
It is likely that many seizures result from an imbalance
between this excitation and inhibition.
A focal seizure originates from a paroxysmal discharge in a focal area of the cerebral cortex (often the temporal lobe); the seizure may subsequently spread to the rest of the brain (secondary generalisation) via diencephalicactivating pathways
In genetic generalised epilepsies (GGEs) the abnormal electrical discharges originate from the diencephalic activating
system and spread simultaneously to all areas of the cortex.
Clinical features
Patients can experience more than one type of seizure attack, and it is important to document each attack type and the patient’s age at its onset, along with its frequency, duration and typical features.Any triggers should be identified .
The type of seizure, other clinical features and investigations can then be used to determine the epilepsy syndrome.
Trigger factors for seizures
To classify seizure type, the clinician should askfirstly whether
there is a focal onset
secondly whether the seizures conform
to one of the recognised patterns .
Classification of seizures (2010 InternationalLeague Against Epilepsy classification)
Where activity remains focal, the classification will be obvious.With generalised tonic–clonic seizures, a focal onset will be heralded by positive neurological symptoms and signs corresponding to the normal function of that area. Occipital onset causes visual changes (lights and blobs of colour), temporal lobe onset causes false recognition (déjà vu), sensory strip involvement causes sensory alteration
(burning, tingling), and motor strip involvement causes jerking.
Focal seizures
1 - Without impairment of consciousness or awareness (was ‘simple partial’):
Focal motor
Focal sensory
Seizures arising from the anterior parts of the frontal lobe may produce bizarre behaviour patterns, including limb posturing, sleep walking or even frenetic, ill-directed motor activity with incoherent screaming.
2 - Awareness may become impaired if spread occurs to the temporal lobes (previously ‘complex partial seizure’). Patients stop and stare blankly, often blinking repetitively, making smacking movements of their lips or displaying other automatisms, such as picking at their clothes. After a few minutes consciousness returns but the patient may be muddled and feel drowsy for a period of up to an hour. The age of onset, preceding aura, longer duration and post-ictal symptoms usually make these easy to differentiate from childhood absence seizures .
Tonic–clonic seizures
An initial ‘aura’ may be experienced by the patient, depending on the cortical area from which the seizure originates .The patient then becomes rigid (tonic) and unconscious, falling heavily if standing and risking facial injury. During this phase, breathing stops and central cyanosis may occur.As cortical discharges reduce in frequency, jerking (clonic) movements emerge for 2 minutes at most.
Afterwards, there is a flaccid state of deep coma, which can persist for
some minutes, and on regaining awareness the patient may be confused, disorientated and/or amnesic.
During the attack, urinary incontinence and tongue-biting may occur.
A severely bitten, bleeding tongue after an attack of loss of consciousness
is pathognomonic of a generalised seizure but less marked lingual injury can occur in syncope.
Subsequently, the patient usually feels unwell and sleepy, with headache and myalgia.
Witnesses are usually frightened by the event, often believe the person to be dying, and may struggle to give a clear account of the episode. Some may not describe the tonic or clonic phase
and may not mention cyanosis or tongue-biting. In less typical episodes, post-ictal delirium, or sequelae such as headache or myalgia, may be the main pointers to the diagnosis.
Absence seizures
• Rare after age 10 years.
• F > M.
• Brief loss of awareness many times a day. Triggered by hyperventilation.
• Remits in adulthood.
• EEG characteristic—3 Hz spike and wave, no photosensitivity.
The attacks are rarely mistaken for focal seizures because of their brevity. They can occur so frequently (20–30 times a day) that they are mistaken for daydreaming or poor concentration in school.
Myoclonic seizures
These are typically brief, jerking movements,predominating in the arms.
In epilepsy, they are more marked in the morning or on awakening from sleep, and tend to be provoked by fatigue, alcohol, or sleep deprivation.
Atonic seizures
These are seizures involving brief loss of muscletone, usually resulting in heavy falls with or without loss of consciousness. They occur only in the context of epilepsy syndromes that involve other forms of seizure.
Tonic seizures
These are associated with a generalised increase in tone and an associated loss of awareness. They are usually seen as part of an epilepsy syndrome and are unlikely to be isolated.Clonic seizures
Clonic seizures are similar to tonic–clonic seizures.The clinical manifestations are similar but there is no preceding tonic phase.
Epilepsy syndromes
Many patients with epilepsy fall into specific patterns, depending on seizure type(s), age of onset and treatment responsiveness: the
so-called electroclinical syndromes .
It is anticipated that genetic testing will ultimately demonstrate similarities in
molecular pathophysiology.
Electroclinical epilepsy syndromes
Common generalised epilepsy syndromesCauses of focal seizures
Idiopathic• Benign Rolandic epilepsy of
childhood
• Benign occipital epilepsy of
childhood
Focal structural lesions
Genetic
• Tuberous sclerosis
• Autosomal dominant nocturnal
frontal lobe epilepsy
• Autosomal dominant partial
epilepsy with auditory features
(ADPEAF)
• von Hippel–Lindau disease
• Neurofibromatosis
• Cerebral migration
abnormalities
Infantile hemiplegia
Dysembryonic
• Cortical dysgenesis • Sturge–Weber syndrome
Mesial temporal sclerosis (associated with febrile convulsions)
Cerebrovascular disease)
• Intracerebral haemorrhage
• Cerebral infarction
• Arteriovenous malformation
• Cavernous haemangioma
Tumours (primary and secondary))
Trauma (including neurosurgery)
Infective
• Cerebral abscess (pyogenic)
• Toxoplasmosis
• Cysticercosis
• Tuberculoma
• Subdural empyema
• Encephalitis
• Human immunodeficiency virus (HIV)
Inflammatory
• Autoimmune encephalopathies
(e.g. anti-voltage-gated
potassium channel antibodies,
anti-NMDA receptor
antibodies, anti-glycine
receptor antibodies)
• Sarcoidosis
• Vasculitis
Causes of generalised tonic–clonic seizures
Generalisation from focal seizures
Genetic
• Inborn errors of metabolism
• Storage diseases
• Phakomatoses (e.g. tuberous sclerosis,
Cerebral birth injury
Hydrocephalus , Cerebral anoxia
Drugs
• Antibiotics: penicillin, isoniazid, metronidazole
• Antimalarials: chloroquine,
mefloquine
• Ciclosporin
• Amphetamines (withdrawal)
• Cardiac anti-arrhythmics:
lidocaine, disopyramide
• Psychotropic agents:
phenothiazines, tricyclic
antidepressants, lithium
Alcohol (especially withdrawal)
Toxins
• Organophosphates (sarin) • Heavy metals (lead, tin)
Metabolic disease
• Hypocalcaemia
• Hyponatraemia
• Hypomagnesaemia
• Hypoglycaemia
• Renal failure
• Liver failure
Infective
• Post-infectious encephalopathy • Meningitis Inflammatory
• Multiple sclerosis (uncommon;
• Systemic lupus erythematosus
Diffuse degenerative diseases
• Alzheimer’s disease uncommonly;
• Creutzfeldt–Jakob disease rarely;)
Investigations
All patients with transient loss of consciousness should have a
12-lead ECG. Where seizure is suspected or definite, patients
should have cranial imaging with either MRI or CT, although
the yield is low unless focal signs are present.
The recurrence rate after a first seizure is approximately 40%
and most recurrent attacks occur within a month or two of the first.
Further seizures are less likely if an identified trigger can
be avoided.
EEG
The EEG may help to establish the type of epilepsy and guide therapy.
An EEG performed immediately after a seizure may be more helpful in showing focal features than if performed after a delay.
Inter-ictal EEG is abnormal in only about 50% of patients with
recurrent seizures, so it cannot be used to exclude epilepsy.
The sensitivity can be increased to about 85% by prolonging recording
time and including a period of natural or drug-induced sleep, but this does not replace a well-taken history.
Ambulatory EEG recording or video EEG monitoring may help with differentiation of epilepsy from other disorders if attacks are sufficiently frequent.
Investigation of epilepsy
Imaging
Imaging cannot establish a diagnosis of epilepsy but identifies any structural cause.
While CT excludes a major structural cause of epilepsy, MRI is required to demonstrate subtle changes such as hippocampal sclerosis, which may direct or inform surgical intervention.
Indications for brain imaging in epilepsy
ManagementIt is important to explain the nature and cause of seizures to patients and their relatives, and to instruct relatives in the first aid management of seizures.
Many people with epilepsy feel stigmatised and may become unnecessarily isolated from work and social life.
It is important to emphasise that epilepsy is
a common disorder that affects 0.5–1% of the population, and that full control of seizures can be expected in approximately 70% of patients.
Lifestyle advice
Patients should be advised to avoid activities where they mightplace themselves or others at risk if they have a seizure. This
applies at work, at home and at leisure. At home, only shallow
baths (or showers) should be taken. Prolonged cycle journeys
should be discouraged until reasonable freedom from seizures
has been achieved. Activities involving prolonged proximity to
water (swimming, fishing or boating) should always be carried
out in the company of someone who is aware of the risks and
the potential need for rescue measures.
Certain occupations, such as firefighter or airline pilot, are not open to those with a previous or active
diagnosis of epilepsy.
How to administer first aid for seizures
• Move the person away from danger (fire, water, machinery,
furniture)
• After convulsions cease, turn the person into the ‘recovery’ position
(semi-prone)
• Ensure the airway is clear but do NOT insert anything in the mouth
(tongue-biting occurs at seizure onset and cannot be prevented by
observers)
• If convulsions continue for more than 5 mins or recur without the
person regaining consciousness, summon urgent medical attention
• Do not leave the person alone until fully recovered (drowsiness and
delirium can persist for up to 1 hr)
Antiepileptic drugs
Antiepileptic drugs (AEDs) should be considered where risk ofseizure recurrence is high.
A diagnosis of two or more seizures is justification enough but a prolonged inter-seizure interval may deter some patients and physicians.
Treatment decisions should always be shared with the patient, to enhance adherence.
A wide range of drugs is available. These agents either increase
inhibitory neurotransmission in the brain or alter neuronal sodium
channels to prevent abnormally rapid transmission of impulses.
In the majority of patients, full control is achieved with a single drug.
Dose regimens should be kept as simple as possible.
Guidelines for choice of antiepileptic drug1
Guidelines for choice of antiepileptic drugs
Guidelines for antiepileptic drug therapyGuidelines for antiepileptic drug therapy
Antiepileptic drugs: dosages, and side-effectsDrug monitoring
• Measuring drug levels is indicated in the following situations:• suspected poor or erratic compliance;
• symptoms of toxicity, e.g. nausea, ataxia, confusion, diplopia.
• Valproate levels are only of use for monitoring compliance. Blood levels do not correlate with therapeutic levels as valproate is highly fat-soluble.
• Carbamazepine and valproate are accepted as first-line
recommendations for partial (with or without 2° generalization) and
generalized seizures, respectively.
• Lamotrigine is used for both types of seizures in women of
child-bearing age.
Drug monitoring
• Phenytoin and phenobarbital are effective but little used because of
long-term side effects. Only indication is in status epilepticus as they can be given IV.
• Clobazam useful adjunct in the short term, especially when cluster
seizures occur, e.g. perimenstrually. Dose, 10–20 mg bd.
• Currently controversy regarding osteopenia/osteoporosis and AEDs,
especially enzyme inducers. Consider bone scan and vitamin D levels
in those with multiple risk factors (age, post-menopause, previous
fractures, poor diet, steroids).
Withdrawing antiepileptic therapy
Withdrawal of medication may be considered after a patienthas been seizure-free for more than 2 years. Childhood-onset
epilepsy, particularly classical absence seizures, carries the
best prognosis for successful drug withdrawal.
Other epilepsy syndromes, such as juvenile myoclonic epilepsy, have a marked tendency to recur after drug withdrawal.
Focal epilepsies that begin in adult life are also likely to recur,
especially if there is an identified structural lesion.
Patients should be advised of the risks of recurrence, to allow them to decide whether or not they wish to withdraw.
If undertaken, withdrawal should be done slowly, reducing the drug dose gradually over weeks or months.
Prognosis with drug treatment
By 12 months 60–70% will be seizure-free.
After 2 years, withdrawal of drugs can be considered. Predictive factors for relapse:
• syndromic epilepsy, e.g. JME.
• underlying structural pathology.
• severe prolonged epilepsy before remission.
• age.
Factors that may affect the decision to stop include driving.
Patients are advised to stop driving during drug withdrawal and for 6 months thereafter.Epilepsy: outcome after 20 years
• 50% are seizure-free, without drugs, for the previous 5 years• 20% are seizure-free for the previous 5 years but continue to take medication
• 30% continue to have seizures in spite of antiepileptic therapy
Surgery
Should be considered, and patients referred to a specialist centre, in cases with:• surgically resectable lesion.
• temporal lobe seizures where there is evidence of mesial temporal sclerosis .
In such patients seizure-free rates are 80%, with 3–4% permanent neurological deficit and 1% mortality rates.
Vagus nerve stimulation
An option with no serious side-effects in those with refractory epilepsy, and unsuitable for surgery.
Status epilepticus
• Continuous seizures.• Two or more seizures with incomplete recovery inbetween.
• Duration > 30 minutes.
Presentation
More common in those with mental handicaps or structural lesions, especially children.In established epilepsy, recent medication reduction/withdrawal, intercurrent illness, metabolic derangement, or progressive disease
should be considered.
Ensure any withdrawn/reduced AEDs are restarted.
If no history of epilepsy consider the following
• Febrile illness (children).• Cerebral infections (e.g. encephalitis, meningitis).
• Space-occupying lesion (e.g. tumour, haematoma).
• Subarachnoid haemorrhage.
• Cerebrovascular disease—haemorrhagic/ischaemic infarcts.
• Metabolic derangement: d glucose, d Na, diCa++.
• Alcohol intoxication/withdrawal.
• Toxicity (e.g. cocaine, carbon monoxide, tricyclic antidepressants).
• Pseudo-status epilepticus—may have a previous history/normal EEG.
Complications of status epilepticus
Management of status epilepticus
Management of status epilepticusContraception
Some AEDs induce hepatic enzymes that metabolise synthetic hormones, increasing the risk of contraceptive failure. This is most marked with carbamazepine, phenytoin and barbiturates, but clinically significant effects can be seen with lamotrigine and topiramate.If the AED cannot be changed, this can be overcome by giving higher-dose preparations of the oral contraceptive.
Sodium valproate and levetiracetam have no interaction with hormonal contraception.
Effects of epilepsy on pregnancy
Increase ×3 complications (bleeding, pre-eclampsia, miscarriage and still birth, IUGR, low birth weight, premature labour).Seizure frequency
No effect in most patients. i seizures usually in those with severe epilepsy.Causes:
• hormonal effects (oestrogen may be epileptogenic, progesterone convulsant and anticonvulsant properties);
• dilutional effect of i plasma volume.
• i metabolism by liver, fetus, placenta.
• d drug absorption due to, e.g. antacids, nausea/ vomiting;
• fatigue, sleep deprivation, anxiety.
New-onset seizures in pregnancy
• Incidence of epilepsy at child bearing age 20–30/100 000. Chance
development occurs due to factors listed earlier.
• i size of meningiomas, AVM, stroke, SAH, cerebral venous thrombosis.
• CT contraindicated. MRI safe.
• Pre-eclampsia and eclampsia:
• most common cause of new onset seizures;
pre-eclampsia (hypertension, proteinuria, oedema, liver dysfunction,
impaired clotting); eclampsia (confusion, focal signs, seizures, coma).
May progress to status epilepticus;
• treatment: magnesium sulfate IV 4g, followed by 10g IM. Then 5g IM
every 4 hours as required.
Management during pregnancy• Measurement of drug levels and dose i as necessary.• Folic acid 5 mg.
Management during labour
• Continue AED (IV if required).
• If high risk of seizures—clobazam 10–20 mg.
• If seizures occur during labour l caesarean section.
Post partum
• Enzyme inducing AEDs d vitamin K-dependent clotting factors with risk of ICH in neonate.• Give neonate 1 mg vitamin K at birth and at 28 days.
• Gradually reduce AED levels to prenatal doses.
Non-epileptic attack disorder(‘dissociative attacks’)
Patients may present with attacks that resemble epileptic seizures but are caused by psychological phenomena and have no abnormal EEG discharges.
Such attacks may be very prolonged, sometimes mimicking status epilepticus.
Epileptic and non-epileptic attacks may coexist and time and effort are needed to clarify the relative contribution of each, allowing more accurate and comprehensive treatment.
Non-epileptic attack disorder (NEAD) may be accompanied by dramatic flailing of the limbs and arching of the back, with side-to-side head movements and vocalising. Cyanosis and severe biting of the tongue are rare but incontinence can occur. Distress and crying are common following non-epileptic attacks.
The distinction between epileptic attacks originating in the frontal lobes and non-epileptic attacks may be especially difficult, and may require videotelemetry with prolonged EEG recordings.
Non-epileptic attacks are three times more common in women than in men and have been linked with a history of past or ongoing life trauma. They are not necessarily associated with formal psychiatric illness.