Atlas of Neonatal Electroencephalography, 3rd Edition

Chapter 7

Neonatal Seizures

The electrographic and clinical characteristics of seizures in the neonate are unique compared with those of older children and adults. In the neonate, interictal epileptiform discharges are rarely present to aid in diagnosis, electrographic seizure patterns vary widely, electrical seizure activity does not always accompany all behaviors currently considered to be seizures, and electrical seizure activity may occur without evident clinical seizures (Kellaway and Hrachovy, 1983; Mizrahi and Kellaway, 1987; Mizrahi and Kellaway, 1998).

This chapter addresses the electroencephalographic (EEG) and clinical features of neonatal seizures. Other pertinent issues concerning neonatal seizures that relate to epileptogenesis of the immature brain, the effect of seizures on the developing brain, pathophysiology, etiology, therapy, and prognosis are beyond the scope of an atlas of neonatal electroencephalography, but are considered in detail elsewhere (Bye et al., 1997; Clancy, 1996; Holmes, 2002; Lombroso, 1996a, 1996b; Mizrahi, 1999, 2001; Mizrahi and Clancy, 2000; Mizrahi and Kellaway, 1998; Mizrahi and Watanabe, 2002; Painter et al., 1999; Rennie, 1997; Scher, 1997, 2002; Stafstrom and Holmes, 2002; Swann, 2002; Swann and Hablitz, 2000; Tharp, 2002; Velisek and Moshe, 2002).

In considering neonatal seizures, important features of interpretation include recognition of EEG seizures and the determination of the significance of focal sharp waves that may occur between seizures. Electrical seizure activity in the newborn has some features similar to those of older children and adults, but also several features characteristic of the neonate. These are discussed later. As previously discussed in Chapters 4, 5 and 6, focal sharp waves in the neonatal EEG may be normal, of uncertain diagnostic significance, or abnormal. However, they generally do not correlate with the presence of epileptic seizures. Thus the finding of isolated sharp waves in an infant suspected of having had a seizure does not provide evidence that a seizure has occurred or will occur.

In addition, the correlation of electrical seizure activity with the occurrence of clinical seizures is critical. This is most effectively accomplished by direct observation at the bedside during EEG recording or by EEG-video monitoring. When the clinical behaviors in question are not witnessed directly or recorded on video, the neurophysiologist must rely on the description of the clinical event through notations made by the electroneurodiagnostic technologist (ENDT) at the time of recording.

CLINICAL CHARACTERISTICS OF NEONATAL SEIZURES

The occurrence of clinical seizures in neonates may often be the first, and sometimes the only, manifestation of central nervous system (CNS) dysfunction. As such, seizure occurrence represents an emergent problem since causes of seizures can be successfully treated, with the potential to limit associated brain injury. Direct or indirect alterations may occur in respiration, heart rate, or systemic blood pressure in association with seizures or their aggressive therapy. Traditionally, it has been believed that seizures in the developing brain do not cause further brain injury beyond that caused by seizure etiology. Although more recent data continue to suggest that the immature brain is more resistant to seizure-induced injury than is the mature brain (Albala et al., 1984; Sperber et al., 1991; Stafstrom et al., 1992; Thurber et al., 1994), recent animal studies also suggest that long-term consequences may result from seizures in the developing brain in terms of disturbances of learning, memory, or behavior (Cilio et al., 2003; de Rogalski et al., 2001;

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Holmes and Ben-Ari, 2001; Holmes et al., 2002; Villeneuve et al., 2000), although this still remains controversial.

The concepts of which motor and autonomic phenomena constitute clinical seizures have continually changed over the years (Burke, 1954; Cadilhac et al., 1959; Dreyfus-Brisac and Monod, 1964; Fenichel et al., 1979; Harris and Tizard, 1960; Kellaway and Hrachovy, 1983; Minkowski et al., 1955; Mizrahi and Kellaway, 1987; Perlman and Volpe, 1983; Rose and Lombroso, 1970; Volpe, 1973, 1989; Watanabe et al., 1977). More recently, greater consensus has occurred. All of the clinical behaviors currently considered neonatal seizures have been recorded and analyzed, using EEG/polygraphic/video monitoring (Biagioni et al., 1998; Bye and Flanagan, 1995; Mizrahi and Kellaway, 1987; Plouin, 2000; Scher et al., 1993). Some behaviors are not consistently accompanied by electrical seizure activity, and many consistently occur without ictal discharges (Mizrahi and Kellaway, 1987). Despite this variable relation of clinical seizures to electrical seizure activity, all clinical seizures occur in association with CNS disorders. These findings indicate that different types of neonatal seizures may reflect different pathophysiologic mechanisms—epileptic or nonepileptic—and regardless of their pathophysiology and relation to electrical seizure activity, the clinical behaviors known as neonatal seizures reliably indicate the presence of CNS dysfunction.

TERMINOLOGY AND CLASSIFICATION

Electroclinical Classification

Although the pathophysiologic mechanisms underlying neonatal seizures may still be debated, it is important to develop a working seizure-classification system that can be effectively used to identify specific abnormal clinical behaviors associated with CNS disease. Regardless of their pathophysiology, all of the phenomena considered to be seizures are “seizures” in the generic sense, without necessarily implying that they are all epileptic. Eventually it may become evident that some “seizures” are epileptic in origin, whereas others are initiated and elaborated by nonepileptic mechanisms.

A number of approaches are used in the classification of clinical neonatal seizures. A classification system based on the relation of EEG seizure patterns to clinical events is presented in Table 7-1 along with other clinical and electrographic signs that may aid in diagnosis (Kellaway and Mizrahi, 1987; Mizrahi and Kellaway, 1987). Table 7-2 lists seizure types, clinical features, electrographic correlates, and presumed pathophysiology. In addition, from the perspective of the neonatal EEG, neonatal seizures can be classified according to the temporal relation between the electrical event and the clinical event: electroclinical, clinical-only, and electrical-only seizures.

TABLE 7-1. Classification of neonatal seizures based on electroclinical findings

Clinical seizures with a consistent electrocortical correlate

 

(Pathophysiology: epileptic)

 

Focal clonic

   

Unifocal

   

Multifocal

   

Hemiconvulsive

   

Axial

 

Focal tonic

   

Asymmetric truncal posturing

   

Limb posturing

   

Sustained eye deviation

 

Myoclonic

   

Generalized

   

Focal

 

Spasms

   

Flexor

   

Extensor

   

Mixed extensor/flexor

Clinical seizures without a consistent electrocortical correlate

 

(Pathophysiology: presumed nonepileptic)

 

Myoclonic

   

Generalized

   

Focal

   

Fragmentary

 

Generalized tonic

   

Flexor

   

Extensor

   

Mixed extensor/flexor

 

Motor automatisms

   

Oral-buccal-lingual movements

   

Ocular signs

   

Progression movements

   

Complex purposeless movements

Electrical seizures without clinical seizure activity

From Mizrahi EM, Kellaway P. Diagnosis and management of neonatal seizures. Philadelphia: Lippincott-Raven, 1998.

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TABLE 7-2. Clinical characteristics, classification, and presumed pathophysiology of neonatal seizures

Classification

Characterization

Focal clonic

Repetitive, rhythmic contractions of muscle groups of the limbs, face, or trunk

   

May be unifocal or multifocal

   

May occur synchronously or asynchronously in muscle groups on one side of the body

   

May occur simultaneously, but asynchronously on both sides

   

Cannot be suppressed by restraint

   

Pathophysiology: epileptic

Focal tonic

Sustained posturing of single limbs

   

Sustained asymmetric posturing of the trunk

   

Sustained eye deviation

   

Cannot be provoked by stimulation or suppressed by restraint

   

Pathophysiology: epileptic

Generalized tonic

Sustained symmetric posturing of limbs, trunk, and neck

   

May be flexor, extensor, or mixed extensor/flexor

   

May be provoked or intensified by stimulation

   

May be suppressed by restraint or repositioning

   

Presumed pathophysiology: nonepileptic

Myoclonic

Random, single, rapid contractions of muscle groups of the limbs, face, or trunk

   

Typically not repetitive or may recur at a slow rate

   

May be generalized, focal, or fragmentary

   

May be provoked by stimulation

   

Presumed pathophysiology: may be epileptic or nonepileptic

Spasms

May be flexor, extensor, or mixed extensor/flexor

   

May occur in clusters

   

Cannot be provoked by stimulation or suppressed by restraint

   

Pathophysiology: epileptic

Motor automatisms

 
 

Ocular signs

Random and roving eye movements or nystagmus (distinct from tonic eye deviation)

   

May be provoked or intensified by tactile stimulation

   

Presumed pathophysiology: nonepileptic

 

Oral-buccal-lingual movements

Sucking, chewing, tongue protrusions

   

May be provoked or intensified by stimulation

   

Presumed pathophysiology: nonepileptic

 

Progression movements

Rowing or swimming movements

   

Pedaling or bicycling movements of the legs

   

May be provoked or intensified by stimulation

   

May be suppressed by restraint or repositioning

   

Presumed pathophysiology: nonepileptic

Complex purposeless movements

Sudden arousal with transient increased random activity of limbs

   

May be provoked or intensified by stimulation

   

Presumed pathophysiology: nonepileptic

From Mizrahi EM, Kellaway P. Diagnosis and management of neonatal seizures. Philadelphia: Lippincott-Raven, 1998, with permission.

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Electroclinical Seizures

Electroclinical seizures are characterized by a temporal overlap between clinical seizures and electrical seizure activity on EEG. In many instances, the electrical and clinical events are closely associated, with the onset and termination of both events coinciding. However, this may not always be the case: clinical onset may precede electrical onset, electrical onset may precede clinical onset, and either the clinical or electrical seizure may terminate first.

Focal clonic, focal tonic, and some myoclonic seizures and spasms are associated with electrical seizure activity. Some clinical features of focal clonic seizures are unique to this age group. The seizures may be multifocal with alternating, asynchronous, or migrating clonic jerking; hemiconvulsive, involving an entire side of the body; or may appear as clonic jerking of axial musculature of trunk, abdomen, neck, or tongue. Focal tonic seizures with asymmetric trunk or limb posturing or tonic eye deviation also are associated with electrical seizure activity. In addition, some focal or generalized myoclonic jerks also are consistently accompanied by EEG seizure discharges. A special, and rare, circumstance is the occurrence of spasms associated with generalized voltage attenuation or generalized slow sharp transients.

Focal clonic seizures most often occur in infants who appear to be awake and alert. Typically, the background EEG activity is normal. The etiologic factors are most often cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage, and, more rarely, metabolic disorders such as hypoglycemia and hypocalcemia. The short-term outcome of infants with focal clonic seizures is good compared with that of infants who have other types of seizures.

Clinical-Only Seizures

Some types of clinical seizures have no specific relation to electrical seizure activity. Those that occur in the absence of any electrical seizure activity include generalized tonic posturing, motor automatisms, and some myoclonic seizures. Generalized tonic posturing may be flexor or extensor or may be mixed extensor/flexor. Motor automatisms include oral-buccal-lingual movements such as lip-smacking, sucking, and tongue protrusion; ocular signs such as roving eye movements, blinking, and nystagmus; progression movements such as pedaling or stepping of legs, or swimming or rotary movements of the arms; and complex purposeless movements such as struggling or thrashing. These clinical events, referred to as “motor automatisms” (Mizrahi and Kellaway, 1987) are equivalent to some described as “little peripheral phenomena” or “anarchic” by Dreyfus-Brisac and Monod (1964); as “subtle seizures” by Volpe (1973); and as “minimal seizures” by Lombroso (1974). Myoclonic jerks also may be present without accompanying EEG seizure discharges. They may be generalized, or they may be confined to limited muscle groups.

Tonic posturing, motor automatisms, and myoclonic jerks most often occur in infants who are lethargic or obtunded. The EEG background activity is typically depressed and undifferentiated. In some infants with these types of seizures, recordings have shown no electrical activity of cerebral origin. The etiology of these seizure types is most often hypoxic-ischemic encephalopathy. Compared with focal clonic and focal tonic seizures, seizures unassociated with electrical seizure activity indicate a poorer prognosis, with high morbidity and mortality.

Electrical Seizure Activity without Evident Clinical Seizures

Subclinical electrical seizure activity—that is, electrical seizure activity with no clinical accompaniment (Clancy et al., 1988; Mizrahi and Kellaway, 1987)—occurs in several situations. This may occur in an infant who is pharmacologically paralyzed for respiratory care. Typically no behavioral changes are associated with seizure discharges of the depressed brain or alpha seizure discharges (see later). Third, antiepileptic drugs (AEDs) may suppress the clinical component of an electroclinical seizure but not the electrical component; the clinical seizure may be controlled, but electrical seizure activity may persist.

Additional Issues of Classification

Seizures That Are Predominantly Autonomic

It has been reported that some clinical seizures consist predominantly of changes in respiration, blood pressure, or heart rate; pupillary constriction or dilatation; pallor or flushing; or drooling or salivation (Mizrahi and Kellaway, 1998). The relation of these paroxysmal autonomic events to electrical seizure activity has not been firmly established, nor has the frequency of their occurrence as ictal phenomena. For example, apnea can occur as an ictal event with associated electrical seizure activity, but this is rare compared with other causes of apnea in newborns. If apnea occurs in close relation to an EEG seizure discharge, it is likely to be accompanied by other clinical seizure phenomena. Thus these autonomic features more likely occur as components of clinical seizures with motor manifestations than as the sole manifestation of a clinical seizure.

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Mixed Seizure Types

Several types of seizures may occur in the same infant: electroclinical, clinical only, and electrical only. For example, an infant with tonic posturing unassociated with electrical seizure activity also may exhibit focal clonic seizures that have a distinct electrical signature. In addition, electrical seizure activity may occur without behavioral correlates in infants who at other times have clinical seizures.

Epileptic Syndromes

Few well-defined epileptic syndromes are found in the neonate (Commission, 1989; Mizrahi and Clancy, 2000); two are benign, and two are catastrophic. The benign syndromes are benign neonatal convulsions and benign familial neonatal convulsions. These are characterized by focal clonic or focal tonic seizures that are electroclinical, have normal-background EEG activity, and typically have a good outcome (Plouin and Anderson, 2002).

Some neonatal seizures are considered idiopathic because no cause can be identified, and no long-term sequelae ensue. Many of these infants are thought to have benign neonatal convulsions, more recently referred to as benign idiopathic neonatal seizures (Plouin, 1990, 1992; Plouin and Anderson, 2002). The infants are typically term and products of normal pregnancy and delivery. The seizures are usually brief, most often clonic, and have their onset between days 4 and 6 of life. Dehan et al. (1977) described an interictal background EEG pattern that may be present in these infants, theta pointu alternant, although it is not considered specific to this disorder (Navelet et al., 1981; Plouin and Anderson, 2002) (see later).

Benign familial neonatal convulsions have a pattern of autosomal transmission based on a locus on chromosome 20 (Leppert et al., 1989; Quattlebaum et al., 1979). Singh and colleagues (1998) identified a submicroscopic deletion of chromosome 20q 13.3 and encoded a novel voltage-gated potassium channel, KCNQ2, as the basis of this disorder. This disorder is now considered to be one of several epileptic disorders characterized as a channelopathy (Noebels, 2001; Leppert, 2001). Benign familial neonatal convulsions had been considered to be benign because initial reports suggested no long-term neurologic sequelae. However, subsequent studies indicate that not all affected infants have normal outcomes (Ronen et al., 1993).

The catastrophic syndromes are early myoclonic encephalopathy (EME) (Aicardi and Goutieres, 1978; Aicardi, 1992) and early infantile epileptic encephalopathy (EIEE) (Ohtahara et al., 1976; Ohtahara et al., 1992). The catastrophic syndromes are compared in Table 7-3 and recently were reviewed by Aicardi and Ohtahara (2002).

TABLE 7-3. Comparison of early myoclonic encephalopathy (EME) and early infantile epileptic encephalopathy (EIEE)

 

EME

EIEE

Age at onset

Neonatal period

Within first 3 mo

Neurologic status at onset

Abnormal at birth or at seizure onset

Always abnormal, even before seizure onset

Characteristic seizure type

Erratic or fragmentary myoclonus

Tonic spasms (early)

Additional seizure type

Massive myoclonus

Partial seizures

 

Partial seizures

Massive myoclonus (rare)

 

Tonic spasms (late)

Background EEG

Suppression burst

Suppression burst

Etiology

Inborn errors of metabolism

Cerebral dysgenesis

 

Familial

Anoxia

 

Cryptogenic

Cryptogenic

Natural course

Progressive impairment

Static impairment

Incidence of death

Very high, occurring in infancy

High, occurring in infancy, childhood, or adolescence

Status of survivors

Vegetative state

Severe mental retardation

   

Quadriplegia and bedridden status

Long-term seizure or syndrome evolution

Tonic spasms

West syndrome

 

Lennox-Gastaut syndrome

From Mizrahi EM, Clancy RR. Neonatal seizures: Early-onset seizure syndromes and their consequences for development. Ment Retard Dev Disabil Res Rev 2000;6:240-241, with permission; based on data from Aicardi J, Ohtahara S. Severe neonatal epilepsies with suppression-burst pattern. In: Roger J, Bureau M, Dravet C, et al., eds. Epileptic syndromes in infancy, childhood, and adolescence, 3rd ed. London: John Libbey, 2002:33-44.

INTERICTAL ELECTROENCEPHALOGRAPHIC FEATURES

Focal Sharp Waves

In older children and adults, a focal sharp wave or spike that may appear between electrical seizures typically indicates the potential for an electrical seizure to arise from that region. However, in the neonate, interictal epileptiform discharges are rarely present to aid in diagnosis. Despite this caveat, isolated sharp waves may arise in the same region of eventual electrical seizure onset, and in these exceptional instances, they are considered epileptiform (Fig. 7-1). However, focal

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sharp waves in the neonate typically are not considered evidence of a focal epileptogenic brain abnormality and therefore provide no useful information concerning the presence or absence of the potential for electrical or clinical seizures in a given infant. Focal sharp waves are discussed in detail in Chapters 5 and 6.

Background EEG Activity

The features of the background activity in infants suspected of having seizures may be helpful in diagnosis. The character of the background activity will provide information concerning the degree, if any, of brain injury and will provide the basis for consideration of possible diagnoses and prognosis (Bye et al., 1997; McBride et al., 2000; Ortibus et al., 1996). When recording infants suspected of having seizures, those with an abnormal background EEG are more likely eventually to have electroclinical seizures than are those with a normal background (Laroia et al., 1998). In neonates with documented clinical seizures, the degree of abnormality of the background activity may be associated with various seizure types: normal EEG background activity is more closely associated with electroclinical seizures, and abnormal background EEG activity is more closely associated with either clinical-only seizures (Mizrahi and Kellaway, 1987) or electrical-only seizures (Mizrahi and Kellaway, 1987; Pinto and Giliberti, 2001). The character of the background activity also may be helpful in the diagnosis of specific epileptic syndromes. The syndromes of EME and EIEE are associated with a suppression-burst pattern (Aicardi, 1992; Ohtahara, 1992). The background EEG activity of some infants with benign neonatal convulsions has been described as a theta pointu alternant pattern (Dehan et al., 1977), although it is not considered specific for the disorder (Navalet et al., 1981; Plouin and Anderson, 2002). This pattern is characterized by generalized theta activity that is occasionally associated with sharp waves. This activity is frequently asynchronous on the sides and occurs discontinuously or in a pattern that alternates with periods of generalized voltage attenuation. The pattern can be present during wakefulness and all stages of sleep. Theta pointu alternant may be present for several days after seizures have resolved. However, it can be associated with well-defined etiologies as well as the syndrome of benign neonatal convulsions.

Ictal EEG Features

Electrical seizure activity consists of sustained rhythmic activity with various morphologies, amplitudes, and frequencies. Electrical seizures are often characterized in terms of their evolution of appearance. The minimal duration of a discharge to be considered an electrical seizure has been defined as 10 seconds (Clancy and Legido, 1987), although this is admittedly arbitrary, and discharges of similar appearance but slightly shorter duration may have the same significance as those of 10 seconds (Oliveira et al., 2000) (Fig. 7-2).

Electrical seizure activity is rare before the age of 34 to 35 weeks CA. The precise CA at which the immature brain can consistently initiate and sustain electrical seizure activity has not been defined and may occur only rarely in the premature infant (Fig. 7-3). With increasing age, however, electrical seizure activity becomes more frequent and of longer duration (Scher et al., 1993).

All electrical seizure activity in the neonate begins focally, except for the generalized activity associated with some types of myoclonic jerks or with infantile spasms. The region of cortical involvement of the electrical seizure activity will determine the motor manifestations of the clinical seizures. The rate of repetition of the discharge will determine the rate of focal myoclonic and focal clonic activity: slower discharges are associated with slow myoclonic movements (Fig. 7-4); faster repetitive discharges are associated with sustained clonic activity (Fig. 7-5); and at times, fastest repetitive discharges are associated with focal tonic activity. Muscle group involvement also will determine clinical manifestations. Smaller muscle groups, with smaller degrees of excursion, may move more quickly in response to rhythmic discharges than do larger muscle groups.

Site of Onset

Electrical seizure activity in the neonate most often arises in the central (Fig. 7-5) or temporal region (Fig. 7-6) of one hemisphere or the midline central region (Fig. 7-7). Less common sites of onset are occipital (Fig. 7-8) and frontal regions (Fig. 7-9).

Focality

Most often, in an individual infant, electrical seizure activity is unifocal—always arising from the same brain region. Seizures also may arise from more than one focal area so that, for example, the electrical seizures may arise from different foci at different times. They also may arise from two or more foci at the same time, but with the two foci firing asynchronously (Figs. 7-10, 7-11 and 7-12).

Frequency, Voltage, and Morphology

Frequency, voltage, and morphology may vary greatly within the same electrical seizure or from one seizure to the next in a given infant. The predominant frequency in a given seizure can be in the alpha, theta, beta, or delta ranges, or a mixture of these. The voltages of the activity also may vary, from extremely low (usually

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when faster frequencies are present) to very high (commonly seen when slow frequencies are present). The morphology of the electrical activity also may vary, consisting only of spikes of various durations, sharp waves, slow waves, or combinations of the waveforms within a given seizure. Examples of the variability of frequency, voltage, and morphology are shown in Figs. 7-13, 7-14, 7-15, 7-16, 7-17 and 7-18.

Involvement of Specific Brain Regions

An individual electrical seizure, once begun, may be confined to a specific region (Fig. 7-19), or it may spread to involve other regions (Fig. 7-20). Spread may be by a gradual widening of the focal area; by abrupt change from a small regional focus to involvement of the entire hemisphere; by migration of the electrical seizure from one area of a hemisphere to another (either in a jacksonian, but most often, in a nonjacksonian fashion); or from one hemisphere to the other.

Evolution of the Discharge

Some electrical seizure activity may begin abruptly with similar frequencies, voltages, and morphology that remain fairly constant throughout the seizure. However, more often, seizures undergo an evolution in appearance with their character changing throughout its course (Figs. 7-21 and 7-22). The changing character throughout an electrical seizure helps in differentiating other nonepileptic rhythmic activity or artifacts from electrical seizure activity.

Special Ictal Patterns

Some unique ictal patterns occur in neonates with severe encephalopathies: electrical “seizures of the depressed brain” and “alpha seizure discharges.” Electrical seizures of the depressed brain are seen in neonates whose background EEG activity is depressed and undifferentiated (Fig. 7-23). The discharges are typically low in voltage, long in duration, highly localized, may be unifocal or multifocal, and show little tendency to spread or otherwise change (Kellaway and Hrachovy, 1983). This seizure pattern typically is not accompanied by clinical seizure activity. The presence of this pattern suggests a poor prognosis.

The sudden but transient appearance of rhythmic activity in the alpha frequency band is referred to as alpha seizure activity (Knauss and Carlson, 1978; Willis and Gould, 1980;Watanabe et al., 1982) (Figs. 7-24 and 7-25). This pattern is characterized by the sudden appearance of rhythmic 8- to 12-Hz, 20- to 70-µV activity typically in one temporal or central region; however, it also can evolve from activity that is more clearly epileptic. In addition, it may occur simultaneously, but asynchronously with other electrical seizure activity (Fig. 7-26). Its presence is indicative of a severe encephalopathy and suggests a poor prognosis. This pattern also may be present in the absence of any clinical seizures. The paroxysmal alpha pattern should be differentiated from virtually continuous rhythmic, low-voltage activity that is a rare finding in the neonate associated with disorders such as congenital heart disease, chromosomal abnormalities, and administration of CNS active drugs (see Chapter 6) (Hrachovy and O'Donnell, 1996).

Generalized Electrical Seizure Patterns

Electrographic events that are considered generalized seizure patterns are rare in the neonate and are associated with only a few specific clinical seizure types. Generalized sharp transients may be associated with generalized myoclonus (Fig. 7-27). Spasms may occur in association with generalized voltage attenuation (Fig. 7-28) or generalized sharp transients.

Electrical Seizure Activity and Medication Effects

The most important effect medication may have on electroclinical seizures is the elimination of clinical seizures while electrical seizures persist. In addition to the occurrence of both electrical seizure activity of the depressed brain and the paroxysmal alpha pattern (e.g., alpha seizure pattern) discussed earlier, electrical seizure activity without clinical seizures may be present in infants treated with AEDs and in those treated with pharmacologic paralytic agents.

A common situation occurs during the short-term administration of AEDs in an infant with electroclinical seizures. This may result first in control of the clinical seizures with persistence of the electrical seizure (Fig. 7-29). The phenomenon has been termed “decoupling” of the clinical from the electrical seizure (Mizrahi and Kellaway, 1987). After continued AED administration, the electrical seizure activity may become modulated and may eventually be eliminated. However, frequently increasing AED dosage or additional agents may not completely eliminate electrical seizure discharges. In instances in which electrical seizures are controlled, they may recur without clinical accompaniment.

Another circumstance in which electrical seizures occur without clinical seizures because of pharmacologic therapy is when infants are paralyzed for respiratory ventilation and other medical reasons. Obviously, an infant who is paralyzed cannot manifest motor signs of seizures.

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LIST OF FIGURES

Focal Sharp Waves

Fig. 7-1. Relation of interictal spikes to seizure activity

Ictal Electroencephalographic Features

Fig. 7-2. Discharge duration defines the seizure

Fig. 7-3. Seizure discharges in the premature infant

Fig. 7-4. Seizure discharges with focal myoclonus

Site of Onset

Fig. 7-5. Central onset of electrical seizure activity

Fig. 7-6. Temporal onset of electrical seizure activity

Fig. 7-7. Midline central onset of electrical seizure activity

Fig. 7-8. Occipital onset of electrical seizure activity

Fig. 7-9. Frontal onset of electrical seizure activity

Focality

Fig. 7-10. Multifocal electrical seizure activity

Fig. 7-11. Multifocal electrical seizure activity

Fig. 7-12. Multifocal electrical seizure activity

Frequency, Voltage, and Morphology

Fig. 7-13. High-voltage seizure activity

Fig. 7-14. Spike morphology of seizure discharges

Fig. 7-15. Spike morphology of seizure discharges

Fig. 7-16. Slow wave morphology of seizure discharges

Fig. 7-17. Slow wave morphology of seizure discharges

Fig. 7-18. Complex morphology of seizure discharges

Involvement of Specific Brain Regions

Fig. 7-19. Highly localized electrical seizures

Fig. 7-20. Spread of electrical seizure activity

Evolution of the Discharge

Fig. 7-21. Evolution in appearance of single electrical seizure

Fig. 7-22. Evolution in appearance of single electrical seizure

Special Ictal Patterns

Fig. 7-23. Seizure discharge of the depressed brain

Fig. 7-24. Alpha seizure discharge

Fig. 7-25. Modulation of an alpha seizure discharge

Fig. 7-26. Alpha seizure discharge coexisting with another seizure discharge

Generalized Electrical Seizure Patterns

Fig. 7-27. Seizure discharges with generalized myoclonus

Fig. 7-28. Generalized voltage attenuation with a spasm

Electrical Seizure Activity and Medication Effects

Fig. 7-29. Response to short-term AED therapy

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FIG. 7-1. Relation of interictal spikes to seizure activity. A: Intermittent low-voltage spikes are present in the left central region; their occurrence waxed and waned in other portions of the recording (not shown). B: Later in the recording, an electrical seizure arose from the same region associated with focal clonic activity of the right arm. The background EEG activity is within the range of normal variation. This EEG is from a 41-week CA infant with a left fronto-parietal lobe infarction.

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FIG. 7-1. (Continued)

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FIG. 7-2. Discharge duration defines the seizure. A brief discharge is present in the midline central region with a duration less than 10 seconds. Some sharp waves occur less regularly after the discharge. The background activity is depressed and undifferentiated in this 40-week CA infant with hypoxic-ischemic encephalopathy.

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FIG. 7-3. Seizure discharges in the premature infant. Segments A-C show continuous recordings. A: An electrical seizure begins in the right occipital region in this 28-week CA infant. B: The discharge persists with gradually reducing amplitude, although the amplitudes are quite high. C: The seizure discharge subsides. D: During the same recording, rhythmic alpha activity occurs in the midline frontal region lateralized to the left. E: This segment is continuous with D and shows the evolution of the seizure activity to recurrent rhythmic bursts superimposed on very high voltage slow sharp waves. No clinical events occurred with any of the electrical seizure activity.

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FIG. 7-3. (Continued)

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FIG. 7-3. (Continued)

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FIG. 7-3. (Continued)

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FIG. 7-3. (Continued)

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FIG. 7-4. Seizure discharges with focal myoclonus. Spike and slow-wave discharges recur at a slow, but regular rate in the right central region. A single, slow, myoclonic flexion of the left arm occurred in close association with each spike and slow-wave discharge. The background activity is within the range of normal variation in this term infant. This is a selected sample from a 12-channel EEG.

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FIG. 7-5. Central onset of electrical seizure activity. Rhythmic sharp waves arise in the left central region and remain confined to that region. This electrical activity occurred with a clinical seizure characterized by clonic activity of the right hand in this 40-week CA infant with a left frontal lobe infarction. When the electrical seizure discharge was correlated with computed tomography findings, the site of ictal onset coincided with the periphery of the lesion, a region that perhaps was more capable of generation of such a discharge than the most devitalized cortex at the center of the infarct. The EEG background activity is within the range of normal variation (not shown).

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FIG. 7-6. Temporal onset of electrical seizure activity. The electrical seizure begins in the left temporal region as low-voltage, fast, rhythmic sharp-wave activity, and then abruptly changes to rhythmic, moderately high voltage, slow activity with sharply contoured waves also involving the posterior region on that side. The seizure is brief, and in the final few seconds of the segments, there is little postictal change. No clinical seizures occurred during this brief electrical event. The interictal EEG background activity is within the range of normal variation (not shown). This sample is from a 40-week CA infant with an intracerebral hemorrhage in the left posterior temporal lobe.

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FIG. 7-7. Midline central onset of electrical seizure activity. Low-voltage, rhythmic sharp-wave activity arises in the midline central region and remains confined to that region throughout the seizure. Little evidence of this activity appears from electrodes covering adjacent brain regions. The background EEG activity is depressed and undifferentiated. The electrical event can be described as a “seizure discharge of the depressed brain.” No clinical seizures occurred in association with the electrical seizure activity. This EEG is from a 38-week CA infant with diffuse cerebral ischemia due to maternal hemorrhage before delivery.

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FIG. 7-8. Occipital onset of electrical seizure activity. Rhythmic sharp waves arise from the left occipital region with evolution to slower rhythmic waveforms not associated with clinical seizures. The interictal background activity is characterized as a suppression-burst pattern. This EEG is from a 40-week CA infant with meconium aspiration, right hemispheric intracerebral hemorrhage, subarachnoid hemorrhage, and congenital syphilis.

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FIG. 7-9. Frontal onset of electrical seizure activity. High-voltage, repetitive, slow sharp waves arise in the right frontal region and, after several seconds, appear as faster and sharper discharges that have spread to the right central region. With electrical seizure onset, a clinical seizure begins, characterized by initial extension of the left arm and leg, followed by clonic jerking of the left hand and foot. The interictal EEG background activity is within the range of normal variation (not shown). This occurred in a 40-week CA infant with trisomy 9 and multiple congenital anomalies, including tetralogy of Fallot, absent right kidney, and dysmorphic facial features.

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FIG. 7-10. Multifocal electrical seizure activity. Seizure discharges occur simultaneously, but asynchronously, in the central regions. No clinical seizures occurred in association with these electrical discharges; the infant had been treated with phenobarbital before EEG recording. The interictal EEG background activity is depressed and undifferentiated (not shown). This EEG is recorded from a 39-week CA infant with hypoglycemia.

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FIG. 7-11. Multifocal electrical seizure activity. Initially, rhythmic, moderate-voltage, sharp-wave activity arises from the right centrotemporal region. Another seizure discharge arises independently from the left temporal region, characterized by sharp- and slow-wave activity with complex morphology. No clinical seizures occurred with these electrical seizures. The EEG background activity is depressed and undifferentiated (not shown). This EEG is from a 39-week CA infant with meconium aspiration, cardiac failure, and persistent cyanosis and hypoxemia requiring extracorporeal membrane oxygenation.

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FIG. 7-12. Multifocal electrical seizure activity. Two seizure foci are present, each with distinct morphology. Rhythmic, slow, moderate-voltage activity is seen in the left occipital region, and independent, low- to moderate-voltage, rhythmic, fast activity in the right temporo-occipital region. The background activity is depressed and undifferentiated (not shown). No clinical seizures occurred with the electrical seizures. This EEG is from a 4-week-old infant, born at 38 weeks GA (42 weeks CA) with pneumococcal meningitis. Neuroimaging revealed bilateral subdural fluid collections, greater on the right; bilateral parasylvian petechial hemorrhages, and bilateral cerebral edema.

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FIG. 7-13. High-voltage seizure activity. High-voltage, repetitive, sharp and slow waves, mixed with some spike and slow waves, are present in the right central region with involvement of all of the hemisphere on that side. A clinical seizure coincided with the electrical seizure discharge and was characterized by focal clonic activity of left leg, face, and hand. The background EEG activity was depressed and undifferentiated (not shown). This EEG is from a 40-week CA infant with subarachnoid hemorrhage.

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FIG. 7-14. Spike morphology of seizure discharges. A seizure discharge arises from the right central region consisting of repetitive spike discharges occurring in association with a clinical seizure characterized by focal clonic activity of the left foot. This EEG is from a 41-week CA infant with group B streptococcal meningitis and associated cerebral infarction of the right posterior temporal and occipital lobes.

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FIG. 7-15. Spike morphology of seizure discharges. Repetitive spike and slow waves arise in the right centrotemporal region in association with a clinical seizure characterized by left arm, leg, and face focal clonic activity. The interictal background activity was within the range of normal variation for age (not shown). This EEG is from an 8-week-old, 34-week GA (42-week CA) infant with nonaccidental head trauma resulting in an intracerebral hemorrhage in the right frontal lobe.

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FIG. 7-16. Slow wave morphology of seizure discharges. Rhythmic, moderate-voltage, 3-Hz activity is present in the right central region and evolves to seizure activity, which is high in voltage, slower, and mixed with spike discharges. This occurred in association with focal clonic activity of the left hand. The background EEG activity is depressed and undifferentiated. This EEG is from a 38-week CA with meconium aspiration, persistent hypoxemia, and extracorporeal membrane oxygenation support.

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FIG. 7-17. Slow wave morphology of seizure discharges. High-voltage, slow rhythmic activity, mixed with occasional spikes, is present in the left central region and occurred in association with the focal clonic activity of the face, arm, and leg on the right. The interictal EEG background activity is within the range of normal variation (not shown). This EEG is from a 42-week CA infant with intraventricular hemorrhage in the left lateral ventricle near the head of the caudate and cerebral edema in the left frontal lobe adjacent to the hemorrhage.

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FIG. 7-18. Complex morphology of seizure discharges. Right central seizure discharges characterized by rhythmic slow activity with superimposed waves of faster frequency. Independent electrical seizure activity is seen in the right temporal region, consisting of rhythmic sharp waves that do not appear to be reflected in the activity of the central focus. This is associated with a clinical seizure characterized by focal clonic activity of the left arm and leg. The EEG background activity is within the range of normal variation (not shown). The EEG is from a 6-week-old, 37-week GA (43-week CA) infant with a history of congenital renal dysplasia and renal failure. The patient experienced a right frontal lobe infarction with evolution to a porencephalic cyst in that region.

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FIG. 7-19. Highly localized electrical seizures. Low-voltage, rhythmic, fast spikes arise in the right temporal region and remain confined to that region throughout the seizure. No clinical events were associated with the seizure discharge. The background EEG activity is depressed and undifferentiated. The EEG is from a 40-week CA infant with chronic hypoxemia due to congenital heart disease that included transposition of the great vessels. The patient was treated by balloon atrial septostomy.

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FIG. 7-20. Spread of electrical seizure activity. Electrical seizure activity begins in the midline central region (Cz) and then shifts to the left central region (C3), with less involvement at Cz. No clinical seizures were associated with the electrical seizure. The background EEG activity was characterized as suppression-burst (not shown). This EEG is from a 40-week CA infant with hypoxic-ischemic encephalopathy, persistent pulmonary hypertension, hepatic failure, and disseminated intravascular coagulation.

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FIG. 7-21. Evolution in appearance of a single electrical seizure (A-H). These samples of three selected channels of a 12-channel EEG show a single electrical seizure from beginning to end. The seizure is confined to the left temporal with a changing morphology of the waveforms. No clinical seizures were associated with these electrical seizures. The background activity is depressed and undifferentiated (not shown). This EEG is from a 40-week CA with meconium aspiration, hepatic and liver failure, hypoglycemia, and hypoxic-ischemic encephalopathy.

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FIG. 7-21. (Continued)

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FIG. 7-22. Evolution in appearance of a single electrical seizure (A-H). One electrical seizure that lasts approximately 80 sec is shown in eight contiguous samples. The seizure begins as low-voltage rhythmic theta activity in the left central region. A change in frequency and morphology is seen throughout the seizure discharge. The background EEG activity is undifferentiated. This EEG is from a 3-week-old infant, born at 40 weeks GA (43 weeks CA) with pyloric stenosis, intractable vomiting, and multiple electrolyte metabolic disorders.

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FIG. 7-22. (Continued)

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FIG. 7-23. Seizure discharge of the depressed brain. Low-voltage, rhythmic, monomorphic, slow sharp waves on the left persist virtually unchanged during the recorded seizure. No clinical seizures occurred during the electrical seizure. The background EEG is depressed and undifferentiated. This EEG is from a 38-week CA infant with persistently low Apgar scores, acidosis, subsequent multisystem organ failure, and hypoxic-ischemic encephalopathy.

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FIG. 7-24. Alpha seizure discharge. An alpha seizure discharge arises abruptly from the right temporal region, characterized by rhythmic sinusoidal activity. No clinical seizures were associated with this electrical seizure. The background activity is depressed and undifferentiated. This EEG is from a term infant with hypoxic-ischemic encephalopathy.

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FIG. 7-25. Modulation of an alpha seizure discharge. A: A seizure discharge is present in the left temporal region characterized by sinusoidal 10- to 11-Hz rhythmic activity that evolved from rhythmic sharp-wave activity. Independent, semiperiodic slow-wave transients also are present in the left occipital region. No clinical seizures occurred during these electrical seizures. The background activity is depressed and undifferentiated. This EEG is from a 38-week CA with postnatally acquired pneumococcal meningitis.B: Later in the same recording the electrical seizure modulated abruptly. As before, no clinical seizures occurred during these electrical seizures.

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FIG. 7-25. (Continued)

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FIG. 7-26. Alpha seizure discharge coexisting with another seizure discharge. A seizure discharge characterized by rhythmic 8-Hz sinusoidal activity evolves from rhythmic, slow, sharp-wave activity in the left temporofrontal region. Approximately halfway through this segment of EEG, an independent seizure discharge arises in the right temporal region consisting of low-voltage, rhythmic, slow, monomorphic sharp waves that can be characterized as seizure discharges of the depressed brain. No clinical seizures accompanied these electrical seizures. The background EEG activity is depressed and undifferentiated (not shown). This EEG is from a 12-week-old, former 26-week GA (38-week CA) infant who was initially hospitalized throughout the first 10 weeks of life and then discharged. He was readmitted 2 weeks later with nonaccidental head trauma with computed to-mography-demonstrated diffuse and bilateral cerebral edema; focal parenchymal hemorrhages in the left temporal, parietal, and occipital lobes; and posterior fossa subarachnoid hemorrhage.

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FIG. 7-27. Seizure discharges with generalized myoclonus. High voltage generalized transients are associated with myoclonic seizures characterized by brief, axial movements involving the trunk and shoulders. There is increased activity in the electromyogram channel after the occurrence of each generalized transient. Some bursting occurred in the absence of myoclonic movements (not shown). The background activity is characterized by a suppression-burst pattern. This EEG is from a 36-week CA infant with lissencephaly.

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FIG. 7-28. Generalized voltage attenuation with a spasm. This infant had a generalized flexor spasm during this brief EEG sample. It was associated with a generalized voltage attenuation. This EEG is from a 39-week CA infant with meconium aspiration, persistent pulmonary hypertension, and hypoxic-ischemic encephalopathy.

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FIG. 7-29. Response to short-term antiepileptic drug (AED) therapy. A: Electrical seizure activity arises from the right central region and clinically is associated with a focal clonic seizure of the left arm. This sample of the EEG was recorded before AED therapy. B: The infant then received phenobarbital (loading dose, 20 mg/kg, i.v.) and had no further clinical seizures. However, later during continued EEG recording, a recurrence of the electrical seizure activity was seen in the same region as that before AED therapy. No clinical seizures occurred during this electrical seizure. This is considered a “decoupling” of the clinical seizures from the electrical seizures. This EEG is from a 40-week CA infant with a region of focal cortical dysplasia in the right parietal lobe near the midline. (From Hrachovy RA, Mizrahi EM, Kellaway P. Electroencephalography of the newborn. In: Daly DD, Pedley TA, eds. Current practice of clinical electroencephalography, 2nd ed. New York: Raven Press, 1990:201-241, with permission.)