Neonatal Seizures

CHAPTER 7


images


Neonatal Seizures


The electrographic and clinical characteristics of seizures in the neonate are unique compared to 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 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, 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; Ellenberg et al., 1984; Glass, 2014; Hellstrom et al., 2015; Holmes, 2002; Holmes 2009; Holmes et al., 2002; Lombroso, 1996a, 1996b; McBride et al., 2000; Mizrahi, 1999, 2001; Mizrahi and Clancy, 2000; Mizrahi and Kellaway, 1998; Mizrahi and Watanabe, 2002; Ortibus et al., 1996; 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; Watanabe, 2014).


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 are characteristic of the neonate. These are discussed later. As previously discussed in Chapters 4 through 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 seizures 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 may often be the first, and sometimes the only, manifestation of central nervous system (CNS) dysfunction in the neonate. As such seizure occurrence represents an emergent problem since some 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 clinical seizures or with their aggressive therapy. While data suggest that the immature brain may be more resistant to seizure-induced injury than the mature brain (Albala et al., 1984; Sperber et al., 1991; Stafstrom et al., 1992; Thurber et al., 1994), recent data suggest that there may be both short-term and long-term consequences of seizures in the developing brain (Cilio et al., 2003; de Rogalski et al., 2001; Holmes and Ben-Ari, 2002; Holmes et al., 2002; Villeneuve et al., 2000).


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; Hrachovy and Kellaway, 1983; Minkowski et al., 1955; Mizrahi and Kellaway, 1987; Perlman and Volpe, 1983; Rose and Lombroso, 1970; Volpe, 1973; Watanabe et al., 1977). More recently, there has been greater consensus. All of the clinical behaviors currently considered as neonatal seizures have been recorded and analyzed, utilizing EEG/polygraphic/video monitoring in studies of characterization as well as seizure surveillance (Andropoulos et al., 2010; Biagioni, et al., 1998; Boylan et al., 2013; Bye and Flanagan, 1995; Clancy et al., 2005; Mizrahi and Kellaway, 1987; Plouin, 2000; Scher et al., 1993; Pressler and Mangum, 2013; Pisani et al., 2008; Nagarajan et al., 2011a). Some behaviors are not consistently accompanied by electrical seizure activity, and many behaviors consistently occurred without ictal discharges (Mizrahi and Kellaway, 1987). Despite this variable relationship of clinical seizures to electrical seizure activity, all clinical seizures occurred in association with CNS disorders. These findings indicate that different types of neonatal seizures may reflect different pathophysiological 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 (Boylan et al., 1999).


TERMINOLOGY AND CLASSIFICATION


Electroclinical Classification


Although the pathophysiologic mechanisms underlying neonatal seizure may 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 neonatal seizures. A classification system based on clinical features is presented in Table 7.1 along with other clinical signs that may aid in classification and the determination of their presumed pathophysiology (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 relationship between the electrical event and the clinical event: electroclinical seizures (an overlap in time of electrographic seizures and clinical seizures with close correlation), clinical-only seizures (with no concurrent electrographic seizures), and electrical-only seizures (with no concurrent clinical seizures).


Electroclinical Seizures

Electroclinical seizures are characterized by a temporal overlap between clinical seizures and electrical seizure activity on EEG. In many instances, the electrical seizure 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 the trunk, abdomen, neck, or tongue. Focal tonic seizures with asymmetrical trunk or limb posturing or tonic eye deviation are also associated with electrical seizure activity. In addition, some focal or generalized myoclonic jerks also are consistently accompanied by EEG seizures discharges. A special, and rare, circumstance is the occurrence of spasms associated with generalized voltage attenuation or generalized slow transients.


Focal clonic seizures may occur in infants who appear to be awake and alert and with an EEG background activity that may be normal. The etiological factors are most often 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 infants who have other types of seizures based upon the degree and distribution of accompanying brain injury.


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, motor automatisms, and some myoclonic seizures. Generalized 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” Dreyfus-Brisac and Monod (1964), as “subtle seizures” by Volpe (1973), and as “minimal seizures” by Lombroso (1974). Myoclonic jerks may also be present without accompanying EEG seizure discharges. They may be generalized, or they may be confined to limited muscle groups.


Table 7.1 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 asymmetrical posturing of the trunk
Sustained eye deviation
Cannot be provoked by stimulation or suppressed by restraint
Pathophysiology: epileptic


Generalized tonic


Sustained symmetrical 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






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. The etiology of these seizure types is most often hypoxic-ischemic encephalopathy. Compared with focal clonic seizures, clinical seizures without electrical seizure activity are more often associated with 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 seizures discharges (see later). Third, antiepileptic drugs (AEDs) may suppress the clinical component of the electroclinical seizure but not the electrical component: The clinical seizure may be controlled but electrical seizure activity may persist.


Additional Issues of Classification


Seizures With Autonomic Nervous System Features

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 or the frequency of their occurrence as ictal phenomena have not been firmly established. 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 motor or behavioral seizure phenomena. Thus, autonomic features more likely occur as components of clinical seizures with motor manifestations than as the sole manifestation of a clinical seizure.


Mixed Seizure Types

Several types of clinical seizures may occur in the same patient: electroclinical, clinical only, and electrical only. For example, an infant with tonic posturing unassociated with electrical seizure activity may also 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 either with or without electrical seizure discharges.


Table 7.2 Classification of Neonatal Seizures Based Upon Electroclinical Findings












CLINICAL SEIZURES WITH A CONSISTENT ELECTROCORTICAL SIGNATURE (PATHOPHYSIOLOGY: EPILEPTIC)


Focal clonic


   Unifocal


   Multifocal


   Hemiconvulsive


   Axial


Focal tonic


   Asymmetrical truncal posturing


   Limb posturing


   Sustained eye deviation


Myoclonic


   Generalized


   Focal


Spasms


   Flexor


   Extensor


   Mixed extensor/flexor


 


CLINICAL SEIZURES WITHOUT A CONSISTENT ELECTROCORTICAL SIGNATURE (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






Epileptic Syndromes

Few well-defined epileptic syndromes are found in the neonate (Berg et al., 2010); they range in severity from benign to those associated with poor outcomes. One of these syndromes is benign familial neonatal seizures. The seizures 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 Neubauer, 2012). There is 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 20q13.3 and encoded a novel voltage-gated potassium channel, KCNQ2, as the basis of this disorder. The disorder had been considered benign because initial reports suggested no long-term neurologic sequelae. However, subsequent studies indicated that not all affected infants have normal outcomes (Ronen et al., 1993).


Until recently, another benign syndrome, benign neonatal seizures, was recognized, but this designation has been eliminated as etiologies for these seizures have been identified (Berg et al., 2010). When considered as a syndromic group, these infants had also been characterized as having benign neonatal convulsions or benign idiopathic neonatal seizures (Plouin, 1992; Berg et al., 2010; Plouin and Anderson, 2002). As a group, the infants are typically full-term and products of normal pregnancy and delivery. The seizures are usually brief, most often clonic, and have their onset between 4 and 6 days of life. Dehan et al. (1977) described an interictal background EEG pattern that may present in these infants as theta pointu alternant, although it not considered specific to this disorder (Navelet et al., 1981; Plouin and Anderson, 2002) (see “Background EEG Activity” later).


There are two epileptic syndromes in the neonate associated with poor outcomes: early myoclonic encephalopathy (EME) (Aicardi, 1992; Aicardi and Goutieres, 1978) and early infantile epileptic encephalopathy (EIEE) (Ohtahara et al., 1978; Ohtahara et al., 1992). These are described and compared in Table 7.3 and have been reviewed by Aicardi and Ohtahara (2002). These disorders are characterized by suppression burst features on EEG and by early onset clinical seizures: erratic or fragmentary myoclonus in EME and tonic spasms in EIEE. There is a growing body of literature that has identified genetic mutations as the etiology of either syndrome recently summarized by Mizrahi and Milh (2012). Of note is the emerging evidence that a subset of neonates with encephalopathy, suppression burst EEG, and electroclinical seizures of various types have a KCNQ2 mutation and potassium channelopathy (Numis et al., 2014; Serino et al., 2013; Weckhuysen et al., 2012, 2013).


Table 7.3 Comparison of Early Myoclonic Encephalopathy (EME) and Early Infantile Epileptic Encephalopathy (EIEE)




















































































 


EME


EIEE


Age of onset


Neonatal period


Within first 3 months


Neurologic status


Abnormal at birth or at seizure onset


Always abnormal onset even prior to seizure onset


Characteristic seizure type


Erratic or fragmentary myoclonus


Tonic spasm


Additional seizure types


Massive myoclonus


Focal motor seizures


 


Simple partial seizures


 


 


Hemiconvulsions


 


 


Infantile spasms (tonic)


Generalized seizures


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 bed-ridden


Long-term seizure evolution


Infantile spasms


Infantile spasms


 


 


Lennox–Gastuat Syndrome






Source: Based upon data from Aicardi (1992) and Ohtahara et al. (1992).


Interictal EEG Features


Focal Sharp Waves

Only gold members can continue reading. Log In or Register to continue

Mar 8, 2018 | Posted by in PEDIATRICS | Comments Off on Neonatal Seizures
Premium Wordpress Themes by UFO Themes