Psychiatric Manifestations and Treatment of Seizure Disorders

Basic Mechanism and Genetics

Epileptic seizures are caused by abnormal, repetitive firing of neurons. Although multiple etiologies may result in these discharges, it is believed that three key elements are con­tributory: neuronal membrane and ion channel character­istics; reduced action of the inhibitory neurotransmitter γ-aminobutyric acid (GABA); and increased activity of excitatory circuits through glutamate or other excitatory neurotransmitters. Absence seizures are believed to involve an abnormality in the circuitry between the thalamus and the cerebral cortex.

Certain epileptic syndromes, both focal and generalized, follow single-gene Mendelian inheritance patterns. Since 1995, genetic discoveries have linked idiopathic epilepsies to mutations in genes coding for voltage-gated channels, ligand-gated ion channels, and neurotransmitter receptors, as well as genes involved in synaptic vesicle release and the development and migration of neurons. Many other epilepsies with genetic predispositions are likely due to complex multiple-gene inheritance patterns, and targeted pharmacological strategies have not yet emerged from these findings.

Classification of Seizures

The ILAE broadly classifies epileptic seizures into two groups ( Box 77-1 ) : focal (partial) seizures (i.e., those with an initial onset in networks limited to one hemisphere of the brain); and generalized seizures (i.e., those that rapidly engage bilateral distributed networks). A third category consists of seizures that cannot be classified in these two categories.

Classification of Epilepsy by Etiology and Electro-clinical Syndrome

Epilepsy is classified according to its etiology as genetic, structural/metabolic, or unknown. Genetic epilepsies are those believed to be caused by a known or presumed genetic abnormality. These include the channelopathies (e.g., SCN1A mutations). Structural/metabolic causes for epilepsy include acquired lesions, such as tumors, strokes, infections, and trauma, as well as congenital malformations, some of which may be due to known genetic defects (e.g., tuberous sclerosis).

An electro-clinical syndrome is a specific recognizable complex of clinical features defined by age of onset, seizure types, EEG characteristics, and, at times, specific underlying etiologies ( Box 77-2 ). Electro-clinical syndromes can be diagnosed in a minority of patients with epilepsy and are more common among the pediatric epilepsies. The most common syndromes are self-limited and/or pharmaco-responsive and include juvenile myoclonic epilepsy, childhood absence epilepsy, juvenile absence epilepsy, and benign epilepsy with centro-temporal spikes (BECTS).

Generalized Seizures

Although there are multiple distinct types of generalized seizures, seizures are usually classified into three major groups: major motor seizures, absence seizures, and minor motor seizures.

Generalized tonic-clonic (GTC) seizures (also called “grand mal,” generalized convulsive, or major motor seizures) are the most common type of generalized seizure; they also occur when a focal seizure evolves to become secondarily generalized. In a purely GTC seizure, the first component is a loss of consciousness. This is followed by the tonic stage, characterized by contraction of the skeletal muscles, extension of the axial musculature, upward deviation of the eyes, and paralysis of the respiratory muscles due to thoraco-abdominal contractions. Once the tonic stage ends, the patient enters the clonic phase, which is characterized by high-amplitude, low-frequency rhythmic jerking movements lasting typically less than 1 minute. Once the seizure terminates, the patient is usually conscious but confused. If after 5 minutes the patient either does not wake up or has another seizure, the diagnosis of status epilepticus should be considered. Once a patient regains consciousness after a GTC, he or she enters the post-ictal period in which he or she typically falls asleep for up to several hours and wakes up with a headache.

Absence (“petit mal”) seizures are another form of generalized seizures. Absence seizures occur mainly during childhood and are less frequent after puberty. They are characterized by the arrest or suspension of consciousness for 5 to 10 seconds. Parents may not notice the typical brief seizures in an otherwise healthy child, but teachers will report that the child stares absently for short intervals throughout the day. Without treatment, absence seizures may occur up to 70 to 100 times a day, and such frequent blackouts can seriously impair a child's school performance. Absence seizures may sometimes be mistaken for inattention, leading to concern for ADHD. However, the physician can usually confirm the diagnosis by asking the child to hyperventilate, since this maneuver will typically precipitate an attack. Other signs include rhythmic blinking (at a rate of 3 blinks per second) and rudimentary motor behaviors, called automatisms , which also occur in adult temporal lobe epilepsy. Absence seizures are the easiest seizure type to diagnose because of the pathognomic EEG abnormality: a 3 Hz spike-and-wave pattern that is often elicited or accentuated when the child hyperventilates. On the other hand, children with ADHD tend to have greater difficulty staying on task and completing their homework, and episodes of inattention typically do not interrupt play, and are not associated with twitches or automatisms.

Minor motor seizures most commonly involve myoclonic and atonic seizures. Although these seizures usually occur in childhood, adults may experience them. Myoclonic seizures are characterized by sudden, brief muscular contractions that may occur singly or repetitively. They must be distinguished from non-epileptic myoclonus. Unlike myoclonic seizures, atonic seizures are characterized by a loss of muscle tone.

Focal (Partial) Seizures

Focal seizures are conceptualized as beginning within discrete networks limited to one hemisphere and are frequently associated with brain lesions. Surprisingly, focal seizures may also be the result of single-gene mutations. Seizures with focal onset often propagate beyond the seizure-onset zone, and the specific symptoms reflect the functional specialization of the involved cerebral tissues. Thus, a careful history and/or observation of a seizure may provide important clues as to the seizure-onset zone as well as the pattern of propagation. Many focal seizures remain sub-clinical, detectable only with electrophysiological recordings, because they do not involve areas of cortex that produce manifestations observable to others or recognized by the patient. However, testing may reveal specific subtle deficits. A focal seizure may spread to involve both hemispheres and culminate in a generalized tonic-clonic seizure, a process called secondary generalization. Focal seizures are often classified as either simple or complex, depending on whether consciousness is affected, although these terms are not favored in the 2010 ILAE classification report, which recommends the use of the term “dyscognitive” to refer to seizures that affect consciousness or other cognitive domains. Epilepsy patients whose seizures begin focally in a consistent region of the brain may be cured if the seizure-onset zone can be identified and the epileptogenic tissues surgically resected.

The Post-ictal State

Following a seizure, there may be varying degrees of neurologic impairment, the nature and duration of which depend on the type and duration of the seizure, the amount of brain involved in the seizure, and the patient's baseline neurologic function.

There is typically no post-ictal impairment following an absence seizure, despite the apparently large region of cortex involved. Similarly, there is no appreciable post-ictal impairment following many simple partial seizures. Nevertheless, the post-ictal state is often characterized by some degree of dysfunction of the involved brain regions. On EEG, this manifests as regional attenuation and/or slow waves over the involved lobe or hemisphere. This dysfunction tends to resolve gradually over the subsequent minutes to hours after seizure termination. After a focal motor seizure, there may be weakness of the limb involved in the seizure, a phenomenon referred to as Todd's paresis. In an analogous phenomenon, sensory seizures may be followed by a corresponding sensory deficit.

Following a generalized tonic-clonic seizure, a patient is typically lethargic, confused, disoriented and may briefly be difficult to arouse. The patient will gradually regain awareness of his surroundings, but may remain amnestic for a portion of the post-ictal period. The patient may go to sleep following a convulsive seizure and wake up fully recovered. However, patients should be monitored during the post-ictal period to ensure recovery of normal vital signs and gradual return to the baseline state, as persistent abnormalities may indicate ongoing sub-clinical seizure activity.

Post-ictal agitation is not uncommon, and is typically seen during the period of confusion and disorientation. Aggressive behavior is usually not purposeful. For instance, a patient might punch into the air or lash out at people attempting to restrain him, but a targeted attack is unlikely to be secondary to a seizure. Typically, post-ictal aggression can be contained by calmly interacting with the patient and re-orienting him. Wrist or ankle restraints should be avoided unless absolutely necessary due to the potential for injury if another convulsion occurs, but padded side rails may be helpful to prevent patients from getting out of bed. Rarely, small doses of haloperidol may be used to control extremely violent or agitated behavior. Post-ictal confusion and occasionally aggression can be seen following focal temporal lobe seizures as well, and post-ictal wandering is common.

While most patients appear to be back to baseline within a few hours after a seizure, patients often report headache, fatigue, anergia, dysphoria and lack of mental clarity for 1–2 days after a seizure. Post-ictal depressive episodes, manic episodes, and psychotic episodes are occasionally seen (see “ Psychiatric disturbances in epilepsy ”).