EPILEPSY – General Characteristics, Etiology, Pathogenesis, Classification, Partial Seizures, Primary Generalized Epilepsies, Common Epileptic Syndromes, Infantile Spasms, Lennox-Gastaut Syndrome, Benign Rolandic Epilepsy, Febrile Convulsions, Progressive Myoclonic Epilepsies (PME), Reflex Epilepsy, Epilepsy and Pregnancy and Management of Epilepsy
An epileptic seizure is electrophysiologically characterized by abnormal transient and excessive electrical discharge of cerebral neurons and clinically characterized by paroxysmal episodes of loss or excess of motor, sensory, autonomic or psychic functions with or without alteration in consciousness. The abnormal electrical discharges (epileptic or seizure discharges) may involve only a small part of the brain or a much wider area in both cerebral hemispheres. The clinical manifestations of epilepsy correspond to the activation of the brain area(s) affected by the electrical discharges. This explains the wide diversity of clinical forms that a seizure might take. The term epilepsy denotes the peripheral events resulting from the abnormal electrical discharges from the brain, recurring on two or more occasions.
In other words seizure is a symptom and epilepsy is a syndrome. Though epilepsy begins first with a seizure, not all first seizures lead to epilepsy. Seizures may often occur in acute systemic conditions such as metabolic disturbances (hypoglycemia), drug toxicity (chloroquine) and drug withdrawal (diazepam) but usually they do not constitute epilepsy.
ETIOLOGY OF EPILEPSY
In about 70% of cases of epilepsy, no cause can be determined even after extensive investigations (primary or idiopathic epilepsy). In the remaining group the etiology varies and is multifactorial depending upon the age of onset and the type of epilepsy. The causes include a large variety of genetically determined, congenital and acquired conditions. Among the acquired causes CNS infections (encephalitis, meningitis and brain abscess), cerebrovascular diseases (cerebral arteriovenous malformation, cerebral hemorrhage and infarction), perinatal hypoxic ischaemic cerebral damage, head trauma and brain tumours predominate. Drug induced seizures are common.
Most of the centrally acting drugs cause generalized convulsions following parenteral administration at high doses. Likewise, withdrawal of drugs like phenobarbitone, benzodiazepines and also alcohol may precipitate generalised convulsions. The onset of epilepsy due to hereditary, metabolic or genetic disorders like hypocalcemia and aminoaciduria is in childhood. Sturge-Weber syndrome and tuberous sclerosis usually lead to epilepsy in early life. Seizures in the first few days after birth are most commonly due to birth anoxia or neonatal intracerebral hemorrhage. Seizures in the first few weeks of life are due to CNS infections, hypocalcemia or other metabolic disturbances. Onset of seizures after the second week of life usually indicates developmental abnormalities of the brain.
Epilepsy due to birth trauma manifests in childhood but occasionally the first attack may occur in adult life. Cerebral tumours, head trauma, neurotuberculomas, neurocysticercosis, cerebrovascular disease (overt or salient) and presenile dementia are the common causes of late onset epilepsy.
Simple partial seizures starting in adult life should suggest a newly developed focal structural lesion in the brain (e.g. tumour, tuberculoma or cysticercosis). Complex partial seizures are most frequently due to unilateral temporal lobe damage such as mesial temporal sclerosis or hamartomas. Typical absence seizures and generalized tonic-clonic seizures without aura are almost exclusively manifestations of primary generalised epilepsy. Atypical absence and atonic, tonic or clonic seizures usually occur in children with mental retardation and brain damage due to a variety of causes. Myoclonic seizures can be a manifestation of primary generalised epilepsy as well as several other symptomatic epilepsies.
The cortical neurons become abnormally excitable due to differentiation. The cytoplasm and cell membrane of such cells have increased permeability rendering them susceptible to activation by hyperthermia, hypoxia, hypoglycemia, and hyponatremia. Deficiency of the inhibitory neurotransmitter gamma-amino butyric acid (GABA) and disturbance of local regulation of extracellular K+, Na+, Ca2+ or Mg2+ are probably responsible for the membrane instability which leads to abnormal electrical discharge. Transition from normal to epileptiform behaviour of the brain is caused by greater spread and neuronal recruitment secondary to a combination of enhanced connectivity, enhanced excitatory transmission, failure of inhibitory mechanisms and changes in intrinsic neuronal properties. Generalized epilepsies are due to electrical activity occurring throughout the cerebral cortex, because of lowering of seizure threshold. Often this is genetically determined. If unchecked, this electrical discharge spreads to the ipsilateral and contralateral hemisphere across intra and interhemispheric pathways and also to the subcortical structures like basal ganglia and brain stem reticular nuclei, from where the excitatory activity is fed back to the rest of the cortex.
CLASSIFICATION OF EPILEPSIES
The classification of epilepsy has undergone several changes from time to time and it is likely that further changes may follow. To standardize the classification, the International League Against Epilepsy has suggested the following two classifications:
1. Classification of epileptic seizures: This is largely based on the seizure type and to a lesser extent on EEG findings. In this classification, seizures are divided into two main categories depending upon the location of the initial epileptic discharge in the brain, i.e. localized to a small area (partial seizures) or larger areas in both hemispheres (generalised seizures).
2. Classifications of epilepsies and epileptic syndromes: This is based on clinical manifestations, age of onset, genetic predisposition, associated neurological and other abnormalities, response to specific anti-epileptic drugs and overall prognosis.
Classification of Epileptic Seizures
A. Simple partial seizures
1. with motor manifestations
2. with somatosensory or special sensory manifestations
3. with autonomic manifestations
4. with psychic manifestations.
B. Complex partial seizures
1. with simple partial features at onset followed by impairment of consciousness
2. with impairment of consciousness at onset.
C. Partial seizures evolving to secondarily generalized seizures
1. simple partial seizure – generalised seizure
2. complex partial seizure – generalised seizure
3. simple partial seizure – complex partial seizure – generalised seizure.
A. Absence seizures
B. Myoclonic seizures
C. Clonic seizures
D. Tonic seizures
E. Tonic-clonic seizures
F. Atonic seizures
CLASSIFICATION OF EPILEPSIES AND EPILEPTIC SYNDROMES
1. Localization related (focal, local, partial) epilepsies and syndromes
1.1 Idiopathic with age related onset
Benign childhood epilepsy with centrotemporal spikes
Childhood epilepsy with occipital paroxysms
Primary reading epilepsy
Chronic progressive epilepsia partialis continua of childhood
Syndromes characterized by seizures with specific mode of precipitation
Temporal lobe epilepsies
Frontal lobe epilepsies
Parietal lobe epilepsies
Occipital lobe epilepsies
2. Generalised epilepsies and syndromes
2.1 Idiopathic with age related onset
Benign neonatal familial convulsions
Benign myoclonic epilepsy of infancy
Childhood absence epilepsy (pyknolepsy)
Juvenile absence epilepsy
Juvenile myoclonic epilepsy (impulsive petit mal)
Epilepsy with grand mal seizures on awakening
Other generalised idiopathic epilepsies not defined above
Epilepsies with seizures precipitated by specific modes of activation
West syndrome (infantile spasms, Salam seizures)
Epilepsy with myoclonic/astatic seizures
Epilepsy with myoclonic absences
2.3.1 Nonspecific etiology
Early myoclonic encephalopathy
Early infantile epileptic encephalopathy with suppression burst
Other symptomatic generalised epilepsies
2.3.2 Specific syndromes
Epilepsies, which form part of the clinical profile of certain neurological disorders
3. Epilepsies and syndromes, undetermined whether focal or generalised
3.1 With both generalised and focal seizures
Severe myoclonic epilepsy of infancy
Epilepsy with continuous spike and wave during slow wave sleep
Acquired epileptic aphasia
Other undetermined epilepsies not included above.
4. Special syndromes
4.1 Situation related seizures
Isolated seizures or status epilepticus
Seizures occurring only when there is an acute metabolic or toxic event caused by factors such as alcohol, drugs, eclampsia and nonketotic hyperglycemia
Partial seizures or focal seizures are due to a small epileptic focus in the brain. They are divided into two main categories.
a. simple partial seizure in which the seizure starts as a focal discharge and remains focal throughout without alteration of consciousness and
b. complex partial seizure when a seizure starts as a focal discharge, but consciousness is also altered or lost.
Simple Partial Seizures
These seizures may have motor, sensory, autonomic or psychic manifestations.
Simple focal or partial motor seizures are due to a discharging epileptic focus in the opposite frontal lobe (motor cortex). These consist of clonic movements of the hand, foot or angle of mouth or turning of the head or eyes. These movements may constitute the entire motor component of the seizure or may be followed by generalised clonic movements and loss of consciousness.
The term jacksonian motor seizures (Jacksonian epilepsy) is applied to the type where clonic contractions start in the fingers of one hand, one side of the face or the foot and slowly spread (march) to the other muscles on the same side of the body. This may or may not be followed by involvement of the opposite side and loss of consciousness. The presence of the characteristic march distinguishes Jacksonian seizures from partial motor seizures. However, both have the same localizing significance.
Complex Partial Seizures
These are defined as focal or partial seizures in which consciousness is impaired or lost. They are frequently due to epileptic discharges in the temporal or frontal lobes. Less commonly they may arise from discharges in other parts of the brain. This forms the single most common type of seizure in adults. The seizure usually consists of complex hallucination of perceptual illusions, indicating its origin from the temporal lobe. The hallucinations are usually auditory and visual but sometimes they may be olfactory or gustatory. The subjects may show increased familiarity (déjà vu) or unfamiliarity ( jamais vu) with the surroundings. In some cases these subjective experiences may constitute the entire seizure. Often this is followed by a period of unresponsiveness, during which the patient exhibits certain automatic behaviour like smacking of the lips or chewing movements (automatism). The patient may walk about or repeat a habitual act. However, when asked a question the unresponsiveness becomes evident.
Sometimes unprovoked aggression or laughter may be the striking feature. The automatism usually lasts for a few minutes, but may sometimes be prolonged. The patient is totally amnesic for the whole period of automatism. The EEG recorded during sleep or hyperventilation may demonstrate the temporal lobe focus. Rarely, other areas of brain like the orbital surface of the frontal lobe or limbic system may be seat of epileptic discharge.
Partial Seizures Evolving to Secondarily
In many cases the generalised seizures are not generalized from their onset. They start as partial seizures, either simple or complex and then soon spread to become generalised, usually as tonic-clonic convulsions. These are called partial seizures becoming secondarily generalised. In such cases the initial manifestations of partial seizures are called “aura” or warning symptoms.
PRIMARY GENERALISED EPILEPSIES
Primary Generalised Seizures
These are seizures in which there is no evidence of an epileptic focus, either clinically or on EEG, as opposed to secondary generalised seizures. The epileptic discharge involves both cerebral hemispheres simultaneously from the onset of the seizures. Hence, consciousness is almost invariably impaired or lost at the onset of the attack.
Generalised seizures are divided into several clinical types and some patients may suffer from more than one seizure type. Atypical seizure patterns may also occur, especially if the patient is on treatment.
Tonic Clonic Seizures
These are also called grand mal epilepsy. The seizure attack occurs in different stages sequentially. The stages may be subdivided into the prodromal phase, tonic phase, clonic phase and the postictal phase. The prodromal phase may start several hours before the ictus (fit). It consists of several subjective phenomena like depressed or apathetic mood, irritability, vague abdominal cramps or other funny sensations, which are easily recognised by the patient. In many instances there is no aura and the patient gets the attack without any forewarning. Presence of aura suggests the nature of the seizure as of focal onset (i.e.) partial seizure.
The tonic phase consists of rolling up of the eyes associated with stiffening of the limbs followed by clenching of the jaws, often resulting in injury to the tongue. The attack may be heralded by an epileptic cry as the entire musculature goes into spasm forcing air through the closed vocal cords. The patient becomes cyanosed due to spasm of respiratory muscles. This phase lasts for about 10 to 30 seconds.
The tonic phase is followed by clonic phase characterized by alternate flexion-extension movements of all the four limbs (convulsions), strenuous breathing, sweating, frothing of the mouth and excess salivation. Urine and feces may be voided. The clonic phase usually lasts for 1-2 minutes. This is followed by a deep comatose state, which lasts for about 5 minutes. The pupils slowly begin to react and the patient then resumes speech, but still remains confused. If left undisturbed, he goes into sleep for several hours and often wakes up with severe headache and at times, vomiting. This is the post-ictal phase and the patient does not remember anything that had happened.
Electroencephalogram (EEG) taken during the attack or sometimes even during the intervals shows generalized seizure discharges. The EEG is often normal in the interictal period.
Absence Seizures (Petit Mal)
These are seen mostly in children. These are distinguished by brevity and absence of motor phenomena. The child does not fall. The attacks come on without any warning and consciousness is impaired only for a brief period often < 10 seconds. The child abruptly stops all ongoing motor activity and speech. There is a vacant stare. External stimuli fail to evoke any response from the patient at that period. These attacks usually last for 2-10 sec after which the patient resumes the pre-seizure activity. At times there may be clonic movements of the eyelids or occasionally automatisms like smacking of lips or chewing movements. The attacks can be precipitated by hyperventilation. The attacks occur several times during the day, but they become less frequent or may even disappear in adolescence. Sometimes these may be replaced by tonicclonic seizures.
The EEG abnormality in petit mal epilepsy is diagnostic. It shows classic “three per second” spike and wave generalised discharges.
Juvenile Myoclonic Epilepsy (Myoclonic Jerks)
This term refers to brisk, brief contractions of one or several muscle groups or a single muscle. The movements are jerky, generally abrupt and uncontrollable and render the patient momentarily helpless. The attacks may occur as a single jerk or may recur every few seconds. Recovery from the attacks is immediate and the subject does not lose consciousness.
Juvenile myoclonic epilepsy (JME) starts in early adolescence. Myoclonic jerks occur with or without generalized tonic-clonic seizures. Attacks occur early in the morning on waking up. A small proposition of childhood absence seizures may evolve into JME. Often the myoclonus may be missed or misinterpreted as seizure activity. It is important to make a proper diagnosis since anti-epilepsy drugs such as phenytoin and carbamazapine may worsen the myoclonus.
Myoclonic jerks are not always ‘epileptic in origin, and may occur in many other non-epileptic neurological conditions. The abnormal electrical discharges may arise from the cerebral cortex, brainstem or spinal cord. Myoclonus may be associated with other forms of epilepsy like absences or generalised tonic-clonic seizures.
Myoclonus is seen in a variety of conditions. All types of metabolic encephalopathies like hepatic failure, renal failure, electrolyte disturbances and others may lead to myoclonus. It is an important feature of progressive myoclonic encephalopathy. At times it is precipitated by light, sound and touch stimuli.
These are less common generalised seizures characterized by sudden loss of postural tone and consciousness without any other motor phenomena. This may lead to sudden “drop” of the individual to the floor without any warning.
Atonic seizures have to be distinguished from cataplexy in which the drop attacks are not accompanied by loss of consciousness and syncope.
COMMON EPILEPTIC SYNDROMES
Syn: Salaam spasm (hypsarrhythmia):
This condition is seen in infants below 1 year of age. This is characterized by brief sudden jerky flexion or less commonly extension movements of both arms, neck and torso. Usually these jerks or spasms occur in clusters, precipitated by sudden noise or tactile stimulus and may occur several times in a day. Usually there is evidence of other neurological disorders, secondary cerebral anoxia or birth injury. As the infant grows, the frequency of the spasms comes down but other forms of seizures may supervene. The characteristic EEG pattern is called hypsarrhythmia.
This is an epileptic syndrome with onset between 1 and 6 years of age. It is characterised by mental retardation, and intractable seizures with mixture of tonic, atonic, tonicclonic and atypical absence seizures. EEG shows diffuse slow and spike wave disturbances. The syndrome may occur without any definite cause or may be associated with a variety of neurodevelopmental or metabolic abnormalities in which case the prognosis is poor.
BENIGN ROLANDIC EPILEPSY
This is a common form of partial epilepsy in childhood with onset between 3 and 11 years. It is characterised by attacks of hemifacial twitches sometimes with involuntary vocalizations which may progress to a generalised or unilateral convulsion. These seizures usually or exclusively occur in sleep. The family history suggestive of autosomal dominant inheritance may be available. The EEG abnormality is highly characteristic showing frequent spike discharge in the rolandic area, especially during non-REM sleep. The prognosis is excellent as it is not associated with any other neurological, psychiatric or behavioural disorder and the seizures respond well to anticonvulsant drugs. In some they may remit spontaneously around puberty.
A febrile convulsion may be defined as a brief generalized convulsion occurring during fever in a child in the age group of 6 months to 5 years without pre-existing or concurrent neurological abnormalities or intracranial infection. About 70% of febrile convulsions occur in the age of 6 to 18 months. The convulsions usually last for a few seconds but may extend upto 15 min. At least 5% of children have one febrile fit before the age of 5 years and nearly 25-50% of them have recurrent attacks, but the risk progressively diminishes with age. A strong family history of febrile fits is evident in many cases. The fits usually occur when the rectal temperature rises above 39°C. Generally, the body temperature normalises after the fit. About 4 to 20% cases may develop convulsions even without noticeable fever. Though the risk of developing chronic epilepsy in such children is only about 2%, it is however higher than in the general population. The risk of developing epilepsy in later life is higher in the following groups:
1. When the first febrile convulsion is complicated, i.e. prolonged (> 30 minutes) or localised or is followed by multiple seizures in 24 hours.
2. Presence of neurological abnormalities before or after the onset of convulsion.
In general, the intellectual performance of children who had febrile convulsions does not differ from normal’s but prolonged or recurrent frequent febrile convulsions lead to brain damage and medial temporal sclerosis, which in later life, causes epilepsy.
PROGRESSIVE MYOCLONIC EPILEPSIES (PME)
These are rare, distinctive epileptic disorders with myoclonic seizures, tonic-clonic seizures and progressive neurologic dysfunction, particularly ataxia and dementia. Myoclonic seizures are described as sudden, brief, lightning like jerks that may be generalised or limited to one or more muscle groups. They are not associated with loss of consciousness and are frequently precipitated by stimuli such as movement, bright light or stress. Physiological myoclonus may occur in many normal persons during sleep or in other disease states. This has to be distinguished from PME. A heterogenous group of disorders may give rise to PME.
a. Biochemical disorders: Unverricht-Lundborg disease, Lafora body disease, neuronal ceroid lipofuscinosis, sialidosis, mitochondrial encephalomyopathy, noninfantile neuronopathic Gaucher’s disease, and others.
b. Clinically defined groups: May give rise to seizures West’s syndrome, Ramsay-Hunt syndrome (dyssynergia cerebellaris myoclonica), and others.
Diagnosis of these groups of disorders depends on the clinical patterns, characteristic fundal changes and biopsy studies of the skin, skeletal muscle, liver, rectal mucosa or brain. Study of these diseases is the realm of the specialist. Management consists of accurate diagnosis, genetic counselling and control of myoclonus by sodium valproate or clonazepam.
Epilepsy precipitated by external stimuli has been designated as reflex epilepsy. The common stimuli which precipitate reflex epilepsy in susceptible people are hot water bath of the head, photic stimulation such as flickering light and TV watching, exposure to sunlight, reading, hearing music, startle and eating. Avoidance of precipitating factors and prophylactic anticonvulsants serve to prevent the attacks.
EPILEPSY AND PREGNANCY
One-fourth to one-third of pregnant women with epilepsy get aggravation of seizure tendency during pregnancy. Status epilepticus may complicate 1–2% of epileptics who are in labor. Since drug levels of antiepileptic drugs are lower in many pregnant women, it is better to monitor free drug levels every month during pregnancy. Risks of AED during pregnancy include the following;
First trimester of pregnancy—congenital malformation in child–12.3%
Status epilepticus: generalized convulsions during labour:
— Risk of hypoxia and acidosis for mother and fetus is high.
— Increased rate of neonatal hypoxia, low APGAR scores in the baby.
Pregnant women with epilepsy have higher risks of hyperemesis gravidarum, pre-eclampsia, abruptio placentae and premature labour. Serum AED levels rise after delivery and therefore monitoring is required.
Diagnosis of epilepsy is essentially clinical. History is most important in making the diagnosis. Careful interrogation of witnesses of an attack is essential to determine the nature of the diagnosis. Epilepsy should be differentiated from simple faint and syncopal attacks. The epileptic attack can occur during day or night regardless of the position of the patient. Syncopal attacks usually do not occur in the recumbent posture. Also the occurrence of pallor at the onset, gradual loss of consciousness and prompt return of consciousness on adopting recumbent posture are diagnostic of syncope. In epilepsy loss of consciousness is abrupt and consciousness returns only slowly. Occurrence of post-ictal headache and vomiting should suggest the possibility of epilepsy. So also, occurrence of seizure during deep sleep is a strong point in favour of epilepsy. Occurrence of injuries such as biting the tongue or due to falls should suggest seizure disorder since these are practically absent in hysterical convulsions.
Hysterical attacks should be differentiated by the lack of aura, absence of injuries and incontinence, presence of peculiar grimacing or squirming movements and the retention of consciousness during a motor seizure, which involves both sides of the body. Moreover hysterical convulsions are bizarre and they continue for long periods, as long as the patient is being observed.
Diagnosis of the type of epilepsy depends upon the description of the attack and clinical examination. The epileptic focus and pattern of epilepsy are determined by investigations.
The electroencephalogram (EEG) is the most useful investigation to establish the diagnosis of epilepsy. The EEG gives positive records in 60-90% of cases, if the records are repeated during or after an attack and after 24 hours of sleep deprivation. Refinements in EEG procedure include the use of special electrodes such as sphenoidal, nasoethmoidal, nasopharyngeal and in selected cases, intracerebral electrodes. Photic stimulation, sleep and hyperventilation are measures used to elicit abnormalities in the EEG.
However, normal EEG does not exclude the diagnosis of epilepsy. Conversely, a small number of normal persons may show paroxysmal EEG abnormalities. Thus EEG can be used only as an additional evidence to the clinical diagnosis of epilepsy. So, also its role in predicting remission or selection of antiepileptic drugs is also limited. But in confirmed epileptics with EEG abnormalities, the decision to stop drug therapy can be based on the persistence of the abnormality.
In epilepsy occurring for the first time after 20 years of age, partial epilepsy, presence of focal neurological deficit and in those where the disease is resistant to conventional treatment, further investigations to exclude anatomical abnormalities and space occupying lesions in the brain are indicated. These include CT and MRI scans of brain.
MANAGEMENT OF EPILEPSY
This consists of (i) treatment of the acute convulsions, and (ii) prophylactic management of convulsive and nonconvulsive seizures.
The latter consists of:
1. Removal of precipitating or causative factors.
2. Antiepileptic medication.
3. Social rehabilitation.