Epilepsy

Gregory N. Barnes

S. Todd Callahan

Epilepsy is the most common chronic neurological condition, af-fecting 1% of the adolescent and young adult (AYA) populations. Seizures—the main symptoms of epilepsy—are defined as recurrent electroclinical episodes of disturbed central nervous system (CNS) function. Two-thirds of AYAs with epilepsy have the potential for excellent seizure control with medication.¹ Most patients have a likelihood of eventual remission of their epilepsy but this outcome is dependent on the epileptic syndrome. Advances in basic science, neurogenetics, and clinical research have contributed to a greater understanding of the mechanisms of epilepsies as a cause of neurological disease. New medications and surgical techniques have improved the outcome of intractable epilepsy and reduced the morbidity for all epilepsy patients.²

For the adolescent or young adult who is also navigating the stresses of peer relationships, independence, and body image, epilepsy can be particularly trying. Fear, prejudice, and stigma of epilepsy are common in society, creating even more challenges for AYAs with this disease. The goals of health care of the adolescent or young adult with epilepsy include making an accurate diagnosis of the epileptic syndrome; evaluation of seizure triggers; treatment of underlying etiologies where possible; appropriate use of anticonvulsant drugs; and recognition and treatment of neurocognitive and/or comorbid psychosocial problems.

ETIOLOGY

Seizures are caused by an excessive discharge of a population of cortical neurons. The location and pattern of spread of activity determine the clinical expression. Recurrent, unprovoked seizures are the hallmark of epilepsy. The etiology of epilepsy may be due to genetics or secondary to remote insult to the nervous system. Infection, trauma, metabolic disturbances, drugs, drug withdrawal, or fever may also provoke seizures acutely. Seizures that occur only in the setting of an acute provocation are not generally classified as epilepsy. In some AYAs with epilepsy, situations or specific stimuli such as strobe lights may provoke seizures (reflex seizures).

EPIDEMIOLOGY

The prevalence of epilepsy in the general population is 2 per 250 with a higher prevalence in children. The incidence is 0.7 to 1 per 1,000 in the general population.³ The peak periods for the onset of idiopathic and age-related primary epilepsies are early childhood and adolescence. Epilepsy occurs slightly more often in males than in females (relative risk for males, 1.1 to 2.4 in various studies). In the US and Western Europe, epilepsy is slightly more common among lower socioeconomic groups. Epilepsy is more common in Mexico, South America, and Central America, and in immigrants from these areas in the US, at least partially due to the high incidence of cerebral cysticercosis. Mental retardation, cerebral palsy, and autism are associated with higher rates of epilepsy and lower rates of remission of childhood-onset epilepsy. Epilepsy is associated with an increased risk of death including sudden unexplained death.

CLINICAL MANIFESTATIONS

Table 23.1 lists classifications of seizures, based on the new international classifications.⁴

Seizure Components

The progression of a seizure is characterized by several temporal components:

An infrequent prodrome, which consists of altered behavior or mood occurring hours to days before the actual seizure. The individual may have an altered sensation or psychic symptom occurring just before other ictal manifestations.
The aura is actually part of the seizure, representing a simple partial seizure, usually with sensory, special sensory, or psychic symptoms.
The seizure event may include motor activity.
A postictal phase may include altered neurological function ranging from coma to mild lethargy, hemiplegia to minimal focal motor dysfunction, lasting minutes to 24 hours.

Grand Mal Seizures (Generalized Tonic-Clonic Seizures)

A generalized tonic-clonic seizure may have a brief, nondescript aura followed by the main seizure semiology. The main tonic phase involves forceful, postural contractions in flexion or extension. Usually, the early phase includes the following: early head deviation, a cry at the onset, loss of consciousness, fall to the ground, and biting the tongue or cheeks. In the clonic phase, the individual has bilateral, generally symmetrical, brisk jerking movements. Clonic movements have a discernible fast-slow component, as distinguished from other types of movement (writhing, sustained posturing, random bilateral nonsynchronous movements), which are less likely a part of a convulsion. After the tonic-clonic phase, the patient usually becomes flaccid, with or without incontinence of urine or stool, as the seizure stops. In the postictal state, the
patient is initially unconscious with decreased tone and reflexes. Patients may have fixed pupils. During recovery, a sleeplike state is observed but the patient is responsive to arousal. After recovery, confusion or headaches may be present.

TABLE 23.1 Classifications of Seizures

Generalized seizures: Bilaterally symmetrical, both in clinical and electroencephalographical manifestations, without focal features

Tonic-clonic, generalized convulsive, grand mal
Tonic seizures
Clonic seizures
Absence seizures
1. Simple (impaired consciousness only): Classic petit mal
2. Atypical: Disturbed consciousness plus myoclonic component, automatisms, autonomic component, or abnormality of postural tone
Akinetic (atonic) seizures
Myoclonic seizures

Partial seizures: Clinical and electroencephalographical onset is localized to one part of the brain (focal)

Simple partial seizures: No impairment of consciousness

Motor symptoms
Sensory symptoms
Autonomic symptoms
Special sensory (visual, auditory, olfactory, gustatory)
Psychic symptoms (fear, déjà vu, jamais vu, euphoria)

Complex partial seizures: Partial seizure with impairment of consciousness, includes most seizures described as “psychomotor.” Seizure may begin with impairment of consciousness or as a simple partial seizure and progress to impaired consciousness

Partial with secondary generalization: Either partial simple or complex partial seizures may secondarily generalize, producing a tonic-clonic or clonic convulsion similar to a primary generalized convulsion. A partial simple seizure may progress through a complex partial seizure or directly to a secondarily generalized seizure

Simple partial seizures progressing to generalized seizures
Complex partial seizures progressing to generalized seizures
Simple partial seizures progressing to complex partial seizures, progressing to generalized seizures

Typical Childhood Absence Epilepsy and Other Absence Seizures

Typical absence seizures in AYAs have no prodrome but often cluster after arousal from sleep. With abrupt onset and no aura, absence seizures are brief (3 seconds to 30 seconds) and are characterized by blank staring and loss of consciousness, usually without falling. In typical absence seizures, minor automatisms may be observed including blinking of eyes and movement of fingers. The seizure onset is abrupt and ends with near-immediate return to normal. In atypical absence seizures, the seizures may be (1) associated with automatisms, myoclonic movements, or loss of tone; (2) longer than 30 seconds; and/or (3) characterized by more gradual onset and less-immediate return to normal. After atypical absence seizures, there is no postictal confusion, but amnesia of the seizure is usual. One-third of absence seizures remit during adolescence (more likely in childhood absence epilepsy; less likely in adolescent-onset/juvenile absence epilepsy). The electroencephalogram (EEG) of typical absence seizures shows characteristic 3-Hz spike and wave activity. Other absence syndromes have generalized polyspike wave discharges, slow spike wave (Lennox-Gastaut syndrome), or faster 4- to 5-Hz spike wave (juvenile myoclonic epilepsy [JME] of Janz). Specific epileptic syndromes like JME with onset in adolescence combine absence with myoclonic seizures and occasional grand mal seizures, most prominent on arising in the morning.⁵ Early morning myoclonus may be viewed as “normal” by the patient and not reported without specific questioning. Patients with absence or absence plus myoclonic seizures are more likely to be photosensitive than those with other seizure types. While rare, “Video game”-related seizures are generally limited to these patients.

Myoclonic Seizures

Myoclonic jerks are brisk and irregular and may involve the trunk or extremities, in symmetric or asymmetrical fashion. The amplitude of myoclonic jerks may be small or large enough to cause the patient to fall. Patients are generally aware of the jerks if they are isolated. They may be unaware if myoclonic jerks are part of absence seizures. The differential diagnosis of myoclonic seizures includes tics, nonepileptic myoclonus, and other movement disorders. Myoclonus, usually occurring on rising in the morning, is a characteristic part of JME. Absence or generalized tonic-clonic seizures often occur in these patients. There is no prodrome, aura, or postictal period. The EEG usually shows bursts of spike wave or polyspike and wave in a generalized distribution. Photosensitivity may be demonstrated on EEG using strobe. Myoclonic seizures may be part of an epileptic encephalopathy, such as Lennox-Gastaut syndrome, beginning in early childhood and continuing in adolescence and young adulthood. Photomyoclonus occurs with exposure to a strobe or to strobe-like conditions in AYAs with photosensitive epilepsy. Other generalized seizures may also be present. Various degenerative conditions, including progressive myoclonic epilepsies and subacute sclerosing panencephalitis, may present during adolescence and young adulthood and may be characterized by myoclonic seizures.

Partial Simple Seizures

Benign focal epilepsy of childhood (also known as benign Rolandic epilepsy (BRE)) is the most common cause of focal motor seizures in childhood and early adolescence. Seizures in BRE are partial simple seizures usually involving the face or arm; seizures may secondarily generalize. Episodes are most likely to occur during drowsiness or sleep onset, or upon awakening. Seizures usually resolve by middle adolescence (14 to 16 years of age). Magnetic resonance imaging (MRI) of the brain in BRE is normal. In contrast, the onset of partial simple seizures during adolescence or young adulthood is more commonly associated with structural pathology (e.g., tumor, arteriovenous malformation, head injury, malformation, and stroke).

Sensory phenomena (aura) may be the only manifestation of a brief limited seizure. Most partial simple seizures are focal motor seizures in which consciousness is retained. Speech arrest and drooling may occur with ictal focus in the dominant hemisphere (left brain in the right-handed person). Focal clonic activity may “march” up an extremity or spread from arm to face or arm to leg, or vice versa. After the seizure, headache or postictal hemiparesis (Todd paralysis) may be present. BRE is associated with central temporal spikes, which are more commonly seen in sleep. The central temporal spikes are commonly bilateral, even if all observed seizures were on the same side. Other partial seizures may be associated with spikes or slowing in a unilateral distribution.

Partial Seizures with Complex Symptomatology

Partial seizures with complex symptomatology are seizures of focal onset accompanied by altered consciousness. These seizures may begin at any age. Although still unusual, structural pathology is more common than in generalized epilepsies or benign focal epilepsy of childhood. For instance, mesial temporal sclerosis may cause seizures of temporal lobe origin with onset during adolescence. Patients may report that “they know a seizure is coming,” which may occur hours or days before a partial complex seizure. Headaches and changes in mood and/or appetite may also be reported.

Typical partial complex seizures consist of the following sequence (any of these symptoms may be absent other than the altered state of consciousness):

Initial sensory, autonomic, or psychic symptoms lasting seconds to minutes; common phenomena include fear, déjà vu, “rising feeling” in abdomen, tingling, and visual, auditory, olfactory, or gustatory hallucination. Flushing or pallor may be observed. Consciousness is generally retained, and patient remembers this part of the seizure.
A blank stare combined with impairment of responsiveness and consciousness. The patient is motionless and does not remember events clearly during this phase, if at all.
Automatisms such as hand wringing, picking, lip smacking, walking aimlessly, grunting, gagging, or swallowing. Although destructive or injurious behavior may occur, directed deliberate violence does not. Consciousness is impaired or lost during this phase, and the patient is amnestic of events during this phase.
Complex partial seizures from the frontal lobe may produce thrashing, agitated movements, bicycling leg movements, or pelvic thrusting, which are difficult to distinguish from nonepileptic seizures. After the seizure, confusion, stupor, headache, and lethargy may last seconds to hours.

Seizure triggers include sleep deprivation, alcohol, or drug ingestion. The EEG may demonstrate focal spikes in temporal, frontal, or parietal areas (usually unilateral), but may also be normal. Features that help differentiate various seizures reported as “little seizures” or “staring spells” (partial complex, typical, and atypical absence) are listed in Table 23.2.

ETIOLOGY/DIFFERENTIAL DIAGNOSIS OF SEIZURES

Etiology of Seizures

Symptomatic Seizures (due to Acute Systemic Disturbance or Trauma)

Acute metabolic disturbance (e.g., hypoglycemia, hyponatremia, and hypocalcemia)
Acute CNS infection (e.g., encephalitis and meningitis) or acute stroke
Intoxication (e.g., cocaine, alcohol, “ecstasy,” phencyclidine, ketamine, and inhalants)
Drug or alcohol withdrawal (e.g., prolonged barbiturates, sedatives, and benzodiazepines use)
Acute head trauma (impact seizure and seizure in first few days after significant head trauma)
Convulsive syncope: Brief tonic or clonic movements occurring after primary syncope

TABLE 23.2 Features of Absence and Complex Partial Seizures

Type	Aura	Loss of Consciousness	Duration	Automatisms	Postictal State	Memory of Event	Electroenceph alogram	Associated Abnormalities
Typical absence (Petit Mal)	None	Immediate	5-20 sec	Occasional simple automatisms	None	None	3-Hz spike wave	20% have grand mal seizures as well; mentally normal
Absence atypical	None	Immediate	5-45 sec	Occasional automatisms	None	None	Slow spike wave or polyspike	Myoclonus, drop attacks, grand mal; mental retardation more common
Complex partial	Often	Gradual or partial in some patients	5 sec-5 min	Frequent, more complicated	Frequent	Partial in some patients	Focal spikes	May have secondary generalization; structural lesions may underlie disorder

Acquired (Symptomatic or Secondary) Epilepsies due to Remote History of CNS Insult

Cerebral malformations: Macroscopic or microscopic (cortical dysgenesis)
Intrauterine infections (e.g., cytomegalovirus and toxoplasmosis), perinatal insult, or postneonatal infections (e.g., meningitis, encephalitis, and brain abscess)
Posttraumatic epilepsy
Tuberous sclerosis, brain tumors, and other mass lesions
Vascular malformations and infarctions or cysticercosis
Genetic changes due to progressive or degenerative conditions
Unknown but presumed symptomatic: Epileptic encephalopathies such as Lennox-Gastaut syndrome, and Dravet syndrome

Idiopathic Epilepsy (Also Called Age-Related Epilepsies)

Primary generalized epilepsies (also called genetic generalized epilepsies)
Benign focal epilepsy of childhood

Differential Diagnosis of Paroxysmal Events That May Mimic Seizure Activity

Vasovagal syncope, migraine, or orthostatic hypotension
Cardiac disease: arrhythmias, low-output states, and mitral valve prolapse
Hyperventilation and anxiety states
Sleep disturbances:
- Narcolepsy: Catalepsy, sleep attacks, sleep paralysis, and hypnagogic hallucinations
- Drowsiness or sleep attacks in patients with obstructive sleep apnea or sleep deprivation
- Sleepwalking, rapid eye movement sleep disturbance, and other parasomnias
- Night terrors
- Periodic leg movements in sleep⁶
Movement disorders:
- Tics
- Paroxysmal kinesiogenic choreoathetosis
- Stiff-man syndrome and other syndromes of continuous muscle fiber activity
- Dystonias (paroxysmal torticollis, activity-related dystonias, dystonia musculorum deformans, and drug-related)
- Pseudohypoparathyroidism: AYAs with hypocalcemia secondary to pseudohypoparathyroidism may present with seizure-like episodes that are primarily dystonic
- Restless leg syndrome
Pseudoseizures (nonepileptic seizures)
Episodic “staring” and inattention:
- Attention deficit disorder and
- Disorders of arousal.

Differentiating Grand Mal Seizures from Syncopal Episode

Table 23.3 compares grand mal seizures with syncopal episodes.

Differentiating Nonepileptic Seizures (Pseudoseizures) Versus Epilepsy

Table 23.4 compares pseudoseizures with epilepsy.

EVALUATION

History

Epilepsy is primarily a clinical diagnosis based on the history. The clinician should review the following with the observers of the event:

What was the adolescent or young adult doing before the episode began—sleeping, quiet, watching television, exercising, reading, or anxious? Where and when did the event occur?

TABLE 23.3 Grand Mal Seizures versus Syncopal Episodes

Component	Grand Mal	Syncope
Preictal	May have prodrome; aura may occur at time of loss of consciousness	Variable—may experience faint or dizzy feeling
Ictal	Violent body spasms; often cries out; sweaty appearance; may have incontinence after tonic-clonic component; coma after seizure	No stereotype; no abrupt onset; slowly falls to floor; cold and clammy May have mild twitching
Postictal	Gradual return to consciousness; confusion	Rarely; confusion