Seizures and Epilepsy

What is the etymology of epilepsy ?

Epilepsy comes from the Greek “epi” meaning “upon,” and lambanein meaning to “take hold of.”

What is a seizure and what is epilepsy ?

A seizure is a single event characterized by the abnormal excessive synchronized firing of cortical neurons that usually results in altered sensation, perception, or motor activity. Between 2% and 4% of the population will have a seizure at some point in their lives. Epilepsy is defined as one or more of the following: (1) at least two unprovoked (or reflex) seizures occurring >24 hours apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures; or (3) diagnosis of an epilepsy syndrome. Between 0.5% and 1% of the population currently has epilepsy, and the lifetime risk of epilepsy is about 1% to 2%.

How are seizures classified?

Seizures are classified according to their clinical and electroencephalographic (EEG) characteristics. Classification schemes have been proposed in 1981, 1989, and most recently 2010. Terms from each scheme are still commonly in use ( Table 22-1 ).

What features distinguish focal- from generalized-onset seizures?

Focal seizures start in a specific area of the brain and have clinical and electrographic features that indicate onset from a single unilateral brain region. Generalized seizures appear to arise from both cerebral hemispheres at once. The manifestations of focal seizures depend on the area of the brain involved. Consciousness is likely to be impaired if the focal seizure involves the limbic system or a sufficiently large region of the brain. Focal seizures may then spread to adjacent areas or to contralateral or other more distant regions through thalamocortical and interhemispheric pathways, eventually resulting in secondarily generalized seizures.

What are the clinical features (semiology), EEG patterns, and common causes of seizures from different areas of the brain?

See Table 22-2 .

What causes generalized-onset seizures? At what age do they usually start?

Generalized-onset seizures (i.e., seizures that cannot be localized to one cerebral hemisphere at onset) usually have a genetic predisposition. The seizures typically begin before the age of 20 and are not associated with well-defined auras (an aura is the first subjective symptom of the seizure and represents a focal seizure).

French JA, Pedley TA: Initial management of epilepsy. N Engl J Med 359:166-176, 2008.

Fisher RS, et al.: ILAE official report: a practical definition of epilepsy. Epilepsia 55:475-482, 2014.

Commission on the Classification and Terminology of the International League Against Epilepsy: Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 22:489-501, 1981.

Berg AT, et al.: Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 51, 676-685, 2010.

Construct a chart describing the major types of generalized-onset seizures.

See Table 22-3 .

How can focal seizures with behavioral arrest (focal dyscognitive or complex partial seizures) and absence seizures be differentiated clinically?

Three main features may help to differentiate complex partial from absence seizures:

• 1.

  Complex partial seizures, unlike absence seizures, may be preceded by a well-defined aura.

• 2.

  On average, complex partial seizures last 60 to 90 seconds, whereas absence seizures usually last no more than 30 seconds.

• 3.

  After a complex partial seizure, the patient is usually confused or has some postictal cognitive problem. Absence seizures are not associated with a postictal state, and patients return to their baseline cognitive state at the end of the seizure.

• 4.

  Absence seizures are generally induced by hyperventilation while complex partial seizures are not.

Note : Automatisms can occur with both absence and complex partial seizures.

Define the term epileptic syndrome .

An epileptic syndrome is a constellation of signs and symptoms that may be associated with certain acquired pathologies or etiologies (symptomatic or structural/metabolic), lack an identifiable pathology or etiology (cryptogenic or unknown), or are likely genetic and follow a well-defined and accepted characteristic pattern (idiopathic or genetic). Syndromes may be associated with focal seizures that begin in one area of the cortex (such as mesial temporal sclerosis) or generalized seizures that appear throughout the cortex at onset (such as childhood absence epilepsy). Syndromic classification is useful because it can often predict prognosis and guide antiepileptic drug therapy. The most recent list of epilepsy syndromes is found at the International League Against Epilepsy website ( http://www.ilae-epilepsy.org ).

List the four most common presumed genetic epileptic syndromes.

• 1.

  Febrile convulsions

• 2.

  Benign childhood epilepsy with centrotemporal spikes

• 3.

  Childhood absence epilepsy

• 4.

  Juvenile myoclonic epilepsy

The first three syndromes usually are associated with spontaneous remission with age. Juvenile myoclonic epilepsy persists and usually responds to treatment with antiepileptic drugs.

Describe the Lennox–Gastaut syndrome.

This epileptic syndrome usually begins before age 5 years and is characterized by generalized tonic–axial, atonic, and atypical absence seizures. Many patients also have myoclonic, partial, and tonic–clonic seizures. The EEG is characterized by a slow (2 to 2.5 Hz) frontocentral dominant spike and wave pattern, and patients have developmental delay. The seizures are usually refractory to medication, and status epilepticus is common. About 60% of patients have a clear underlying cause of encephalopathy (symptomatic or structural/metabolic).

Arzimanoglou A, French J, Blume WT, et al.: Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology. Lancet Neurol 8:82-93, 2009.

What are “benign” febrile seizures?

Benign febrile seizures (convulsions) are an inherited predisposition to developing a tonic–clonic seizure with a high fever. The description is limited to convulsions associated with high fever in children younger than the age of 5 years (usually between 6 and 36 months of age), with no cause for the seizure other than the fever. Benign febrile seizures are common, occurring in 3% to 5% of children younger than the age of 5 years. Most patients have only one or two seizures. Recent genetic analysis of families with febrile convulsions has defined specific associated gene defects (see [CR] , Table 22-4 ).

Are febrile seizures a risk factor for the development of epilepsy?

A single, isolated febrile seizure of short duration probably does not greatly influence the later development of epilepsy. The overall risk of developing epilepsy in the general population is approximately 1%, and in those with febrile seizures, the risk increases to approximately 3%. In general, if there are no other reasons to suspect recurrent seizures, such children are not treated. The following features, however, have been identified as risk factors for the development of epilepsy:

• 1.

  Underlying neurologic or developmental abnormality

• 2.

  Family history of nonfebrile seizures

• 3.

  Prolonged febrile convulsions

• 4.

  Multiple febrile convulsions

• 5.

  Atypical or focal features (complex febrile seizures)

Describe the syndrome of benign childhood epilepsy with centrotemporal spikes.

This syndrome accounts for about 15 to 20% of epilepsy cases younger than the age of 15 years. The seizures, which are mostly nocturnal, are associated with focal motor activity of the face with salivation. The seizures may generalize secondarily. Sensory symptoms may occur around the mouth in addition to motor components. Speech may not be possible. The EEG is characterized by a prominent interictal centrotemporal sharp wave with otherwise normal background. The sharp waves occur more frequently during sleep. This epilepsy typically remits spontaneously by the age of 16, regardless of treatment. Treatment for this focal epilepsy may be instituted, depending on how disruptive the seizures are. Therapy is individualized and ranges from no therapy with counseling and observation to chronic antiepileptic drug (AED) therapy.

Characterize juvenile myoclonic epilepsy.

This syndrome is characterized by multiple seizure types including (1) myoclonic seizures that often occur shortly after wakening, (2) generalized tonic–clonic seizures that tend to be precipitated by sleep deprivation, and (3) absence seizures. Interictally, the EEG typically shows a 4- to 6-Hz generalized spike-wave pattern. The generalized myoclonic jerks are associated with a generalized spike-wave discharge, and usually consciousness is not lost. Unlike the other common idiopathic epilepsies, juvenile myoclonic epilepsy does not usually remit with age. Valproate, topiramate, lamotrigine, levetiracetam, and primidone have been successful in treating seizures. Some of the other newer AEDs also may prove to be beneficial.

What systemic physiologic changes occur during a seizure?

For both absence and complex partial seizures, the patient may have a variety of autonomic alterations, including changes in pulse rate, perspiration, salivation, pupillary dilatation, and urinary incontinence. The most dramatic systemic changes occur during generalized tonic–clonic seizures, with increased blood pressure and pulse rate, increased autonomic nervous system activation, metabolic acidosis, and a drop in PO ₂ and increase in PCO ₂ during the apneic tonic phase. Prolonged generalized tonic–clonic seizures may have serious consequences including hyperkalemia or rhabdomyolysis.

What central nervous system physiologic changes occur during a seizure?

During a seizure, cerebral blood flow and glucose utilization in the brain are increased. There may be an accompanying increase in lactate and a decrease in pH, alterations in the concentration of neurotransmitters, an increase in extracellular potassium, and a decrease in extracellular calcium. Generalized tonic–clonic seizures and most complex partial seizures activate the hypothalamus and increase serum prolactin, a finding that may help to differentiate epileptic from nonepileptic (psychogenic) seizures with prolactin level assays postictally. Prolactin also may be elevated after syncope and hence cannot differentiate epileptic seizures from syncope.