Ebook Current practice of clinical electroencephalography (4th edition): Part 2

(BQ) Part 2 book Current practice of clinical electroencephalography presents the following contents: Pediatric epilepsy syndromes, EEG in adult epilepsy, EEG voltage topography and dipole source modeling of epileptiform potentials, subdural electrode corticography, evoked potentials overview, neurophysiologic intraoperative monitoring.

10

DOUGLAS R NORDLI JR

Pediatric Epilepsy Syndromes

Introduction: Differential Diagnosis of Epilepsy According to Prominent EEG Features

The Familial Epilepsies (Epilepsies with Frequently Normal Interictal Backgrounds)

Benign Familial Neonatal EpilepsyBenign Familial Infantile EpilepsyAutosomal Dominant Nocturnal Frontal Lobe Epilepsy

Familial Lateral Temporal Lobe Epilepsy or Autosomal Dominant Epilepsy with Auditory Features

Familial Mesial Temporal Lobe Epilepsy

Genetic Generalized Spike-Wave Epilepsies

Myoclonic Epilepsy in InfancyMyoclonic-Astatic Epilepsy (Doose Syndrome)Childhood Absence Epilepsy

Epilepsy with Myoclonic AbsencesJuvenile Absence Epilepsy

Juvenile Myoclonic EpilepsyMasquerading Conditions

Self-limited Epilepsies with Focal Spikes

Panayiotopoulos SyndromeBenign Childhood Epilepsy with Centrotemporal Spikes or Rolandic Epilepsy

Late-Onset Occipital Lobe EpilepsyConditions Masquerading as Self-limited Epilepsies with Focal Stereotyped Spikes

Epilepsies with Encephalopathy (Epilepsies with Slowed Backgrounds and Multifocal Pleomorphic Spikes)

Epileptogenic EncephalopathiesEpileptic EncephalopathiesWest Syndrome

Late Infantile Epileptic EncephalopathyLennox-Gastaut Syndrome

Focal Structural Epilepsies

Infantile Seizures are Often SubtleThe Terms, “Simple” and “Complex” Are Difficult

to ApplyInfantile Focal Seizures May Have “Generalized”

Clinical FeaturesDifficulty Lateralizing Based upon Clinical FeaturesTypes of Infantile Focal Seizures and Their

Electroclinical Correlations

Conclusions References

Pediatric ePilePsy syndromes

284

for diagnosis These groupings provide some powerful information: if there are genetic predispositions, they predict the mode of inheritance, they in-form about the general prognosis, they have strong treatment implications, and they could be used as the basis for referral to tertiary epilepsy centers

Of course, this is the opposite of the way we as clinicians normally duct our evaluations A precise history and physical examination should

con-always come first It is the sine qua non portion of the epilepsy evaluation,

the basis of all we do, and the most important daily activity of the child neurologist A thorough history elicited with minimal interruption accom-panied by close observation of the child and family allows us to make the interpersonal connections that are critical for trust and healing

The interictal EEG, however, is a remarkably powerful tool and even though it sits in second place to our clinical assessment, it nevertheless informs us about the underlying pathophysiology in a manner that our naked senses never could For many years, our predecessors have appreciated that the various epilepsy syndromes have different relative contributions of genetic and structural components These thoughts were codified in the 2010 publication of the International League Against Epilepsy’s Classification Committee (1) In this chapter, we will see how the interictal EEG informs us about these fundamental characteristics The premise is simple: genetic and structural factors have markedly different EEG signatures, which allows the EEG to effectively categorize the epilepsies Indeed, the EEG findings can

be used as an endophenotype to explore the genetic basis of susceptibility to epilepsy (2) This type of epilepsy syndrome organization is highly practical and simultaneously it reveals some fundamental principles about the causes

of the epilepsies Another remarkable fact is that this can be usually plished with a relatively brief sample of the awake and sleep interictal EEG

accom-THE FAMILIAL EPILEPSIES (EPILEPSIES WITH FREQUENTLY NORMAL INTERICTAL BACKGROUNDS)

One of the five broad categories of EEG features seen in children with

epi-lepsy is a normal tracing The precise percentage of normal EEGs seen in

patients with epilepsy is difficult to determine, but it may be as low as 8% (3) One reason for a repeatedly normal tracing may be a remote location

of an epileptogenic lesion—one that does not readily allow for detection ing conventional scalp recording electrodes Normal tracings are also seen

us-in certaus-in distus-inctive epilepsy syndromes that share a common tic: they are familial epilepsies that are inherited in an autosomal dominant

characteris-TABLE 10.1 Organization of the Epilepsies by EEG Characteristics

Name

EEG background

Epileptiform activity Inheritance

general-Spikes are strongly inherited;

Spikes are strongly inher- ited; epilepsy

is minimally 4a Epileptogenic

Pleomorphic multifocal spikes Pleomorphic multifo- cal spikes;

remental responses

electrodec-If genetic, often

de novo

mutations, some autoso- mal recessive disorders; usu- ally not familial

5 Focal structural

epilepsies

Focal slowing, attenuation,

or both

Pleomorphic focal spikes

Minimal genetic contribution

INTRODUCTION: DIFFERENTIAL DIAGNOSIS OF

EPILEPSY ACCORDING TO PROMINENT EEG FEATURES

An unconventional but effective starting point for an organization of

pe-diatric epilepsies is the interictal EEG As shown in Table 10.1, the various

patterns encountered in clinical practice may be reduced to five discrete

in-terictal EEG groups There are two major domains: the organization of the

background and the characteristics of the epileptiform activity, most

impor-tantly the morphology of the interictal epileptiform discharges (IEDs) By

considering the age of onset, one can narrow down the epilepsy syndromes

to two or three possibilities, and the predominant seizure type will easily

guide one to the final diagnosis In a minority, most particularly the familial

epilepsies, verification of other similarly affected family members is critical

channels, responsible for the M-current (9) This slowly activating current regulates subthreshold neuronal excitability and therefore raises the pos-sibility that a medication like retigabine may be helpful since it blocks the M-current A closely related syndrome of benign neonatal-infantile sei-zures has been associated with a missense mutation in the SCN2A gene, which encodes the alpha-2 subunit of the voltage-gated sodium channel (2q24) (10).

Benign Familial Infantile Epilepsy

BFIE and sporadic forms (which may be similar disorders) have been reported by several different investigators working in different regions of the world (11–14) Affected infants have focal seizures, which may present with subtle behavioral arrest or, on the other extreme, apparent bilateral convulsive features Eye version, staring, oral automatism, and oxygen desaturation are other common elements, and these are commensurate with the location of onset of the seizures The interictal EEG is usually nor-mal, though some BFIEs may have peculiar low- or medium-voltage vertex spikes or sharp waves followed by a slow wave with a dome-like morphology (12,15) Ictal discharges often arise from the temporal region or posterior quadrant This finding is relatively nonspecific, since many focal seizures

in infants arise from the same region These disorders are inherited in an autosomal dominant fashion and several genes have been discovered, which often involve ion channels, but importantly, sometimes do not (16) Defects

in the ATP1A2 gene may cause familial hemiplegic migraine and ated infantile seizures (17) When there is associated paroxysmal kinesigenic dyskinesia, mutations in the proline-rich transmembrane protein (PRPT2) have been reported (18) Similar mutations have been identified in Japa-nese children (19) and even, rarely, have been found in sporadic cases (20) The fact that only 6 of the 16 probands in the Japanese study tested posi-tive indicates that there are clearly other genetic causes of BFIE still to be discovered

associ-Autosomal Dominant Nocturnal Frontal Lobe Epilepsy

Patients with ADNFLE have sudden awakenings with dystonic movements (tonic posturing) or violent movements Since the EEG findings are usually relatively bland, the seizures may be mistaken for sleep disorders, nocturnal paroxysmal dystonia, or nonepileptic seizures Rarely, the interictal EEG may show focal features such as slowing and spikes (21) Ictal recordings

fashion These may be considered the best examples of familial epilepsies

Why these epilepsies most often present with normal interictal backgrounds

is not entirely clear, but certainly, the normal background rhythms speak to

the absence of cognitive impairment and disability in the vast majority of

individuals with these epilepsies Here we encounter the first EEG-epilepsy

paradox: even though these epilepsies are strongly genetically determined

and spikes in other conditions have a strong genetic component (vide infra),

the most conspicuous feature of the background is the lack of interictal

epileptiform activity in these familial epilepsies

There are familial epilepsies for every epoch of pediatric life starting

with the neonatal period, and continuing to infancy, childhood, and

ado-lescence These include benign familial neonatal epilepsy (BFNE), benign

familial infantile epilepsy (BFIE), autosomal dominant nocturnal frontal

lobe epilepsy (ADNFLE), autosomal dominant epilepsy with auditory

fea-tures (ADEAF), and other autosomal dominant temporal lobe epilepsies

It is obvious from the titles of these epilepsies that they vary in age of

pre-sentation, the brain region commonly involved, and the clinical

manifesta-tions Generally, the combination of the clinical features and family history,

along with the mostly normal interictal EEG data, is sufficient to make a

diagnosis, but if confirmation is required, genetic testing can help By and

large, the outcome is favorable, although there are published cases of severe

phenotypes (4)

Benign Familial Neonatal Epilepsy

BFNE usually begins on the second or third day of life and resolves within

the first few months During seizures, neonates may have tonic posturing,

automatisms, apnea, or focal or generalized clonic activity The seizures

may rarely persist into adulthood Typically, the interictal EEG is normal,

though it may have focal or multifocal sharp waves, an excessively

discon-tinuous tracing for age or the theta-pointu alternant pattern The latter is

characterized by rhythmic 4- to 7-Hz activity, with admixed sharp waves,

with shifting laterality across the hemispheres, but it is by no means specific

for this disorder Authors describe a clinical sequence starting with

hyper-tonia and followed by apnea, autonomic signs, facial movements, and limb

clonus (5) In some of the recorded seizures, an electrodecrement heralds

the event and may last up to 19 seconds, followed by 1- to 2-minute

bilat-eral spikes or sharp waves (6), but focal seizures (7) and focal seizures with

secondary spread have also been recorded (8) The disorder has been

asso-ciated with mutations in the KCNQ2 and KCNQ3 voltage-gated potassium

Pediatric ePilePsy syndromes

286

symptoms is usually in adolescence of early adult life, but childhood onset

is also possible It is characterized by subtle seizures with auditory tions, infrequent nocturnal convulsions, and a good response to medications Seizures may be triggered by voices or noises The auditory hallucinations may be humming, clicking, ringing, or other noises Other sensory phenom-ena may also occur The interictal EEG is usually normal, though, as in the other familial disorders, IEDs may rarely be found and sporadic cases ap-pear to have a higher incidence of epileptiform discharges (25,26)

hallucina-Familial Mesial Temporal Lobe Epilepsy

The precise genetic cause of familial mesial temporal lobe epilepsy is not yet known This disorder usually presents in adults, never before age 10 years, and therefore, it will be only briefly mentioned here Seizures tend to be in-frequent, mild, and easily controlled with medication, contrasting them to other forms of mesial temporal lobe epilepsy (27) Seizures without alteration

are more distinctive and are characterized by bifrontal beta activity or other

rhythmic discharges (22) (Fig 10.1) The ictal discharges may lateralize or

even localize to a region, suggesting a focal structural lesion, and therefore,

a careful family history is warranted before considering focal respective

sur-gery in patients with nocturnal frontal lobe seizures Genetic screening for

the associated nicotinic acetylcholine receptor gene mutation (CHRNA4

and CHRNB2) is commercially available

Familial Lateral Temporal Lobe Epilepsy or Autosomal

Dominant Epilepsy with Auditory Features

Ottman described a pedigree in 1995 where most affected members

re-ported seizures with auditory symptoms and named the syndrome

autoso-mal dominant partial epilepsy with auditory features (ADPEAF [OMIM

600512]) (23) Subsequently, it was found that mutations of the leucine-rich

glioma-inactivated 1 LGI1 gene caused this disorder (24) The onset of

Figure 10.1: ictal recording in a 10 year old boy with adnFle note the

sudden change in the background as he awakens from sleep there is some admixed low-voltage rhythmic fast activity in the frontal regions.

myoclonia (Jeavons syndrome), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and epilepsy with generalized tonic-clonic sei-zures alone Treatment is generally with broad-spectrum agents, with the ex-ception of ethosuximide for CAE Patients in this category will also usually not require referral to a tertiary center, unless complications arise or special circumstances present themselves.

Myoclonic Epilepsy in Infancy

The predominant seizure seen in MEI is myoclonus, as the name suggests fants who are developing normally have myoclonic jerks mostly of the head and proximal arms, occurring in isolation or in brief runs of recurrent jerks The ictal EEG shows a burst of generalized or diffuse spike-wave activity with the myoclonia, otherwise the interictal EEG is normal (33) (Fig. 10.2)

In-Myoclonic-Astatic Epilepsy (Doose Syndrome)

Myoclonic-astatic epilepsy may occur between late infancy and 6 years, but most often starts between 2 and 4 years Many children will have antecedent febrile seizures The prototypic seizure is a myoclonic-astatic attack, or now known as a myoclonic-atonic seizure (34) The seizure begins with a sudden jerk of the head or body followed by a sudden loss of tone, causing a head drop or body drop This may easily result in injury because of the combina-tion of the sudden propulsion from the myoclonus, the subsequent loss of postural tone, and the inability to have a protective reflex In addition to this seizure type, atonic seizures, isolated myoclonic jerks, absence seizures, and generalized clonic-tonic-clonic seizures occur Daytime tonic seizures are considered exclusionary by some, but nocturnal tonic seizures do occur, even in patients with excellent outcome

The interictal EEG may show biparietal rhythmic theta activity, and this may be the only abnormality early in the course of the illness (Fig 10.3) Bursts of 2- to 3-Hz generalized spike and polyspike-wave discharges fol-low and are often frequent These occur in brief bursts, usually consisting

of isolated spike waves, couplets, or triplets The repetition rate is therefore difficult to accurately measure, but it is often variable between the bursts Photosensitivity is common

The ictal accompaniment of the myoclonic-astatic seizure is a burst of generalized polyspike-wave discharge, where the after-going slow-wave discharge appears to have some high-frequency attenuation or diminished high-frequency activity (Fig 10.4)

of consciousness are more common than those with dyscognitive features

Many cases show normal imaging and EEG findings, and the presence of MR

changes or interictal epileptiform activity appears to predict intractability (28)

GENETIC GENERALIZED SPIKE-WAVE EPILEPSIES

Individuals with these forms of epilepsy have normal interictal backgrounds

with superimposed generalized spike-wave discharges (SWDs) These

dis-charges will usually be 3 Hz or greater, though, at times, some slower

spike-wave activity, circa 2.5 Hz may be seen, particularly in the younger child In

all cases, these occur on the backdrop of a normally developing child There

may be associated photoparoxysmal responses and some of these epilepsies

will show activation of spike waves with hyperventilation Spikes may

ap-pear more irregular and demonstrate fragmentation in the sleep record It is

not unusual to see focal features (focal slowing and focal spikes), but these

will show shifting laterality from study to study

As stated, the interictal EEG background is normal, but there may be

some important exceptions: rhythmic activity may intermittently

punctu-ate the record This may be seen as either intermittent rhythmic theta

ac-tivity, which is often in the biparietal regions (prominent in many cases of

myoclonic-atonic epilepsy described by Doose) or as intermittent rhythmic

delta, seen in either the occipital or the frontal regions (occipital

intermit-tent rhythmic delta activity [OIRDA] and frontal intermitintermit-tent rhythmic

delta activity [FIRDA], respectively)

Generalized spike waves and other paroxysmal features found in the EEGs

of individuals with these epilepsies have been known for some time to be

inherited in an autosomal dominant fashion with variable penetrance so that

a high proportion of family members of individuals with primary

general-ized epilepsy will have generalgeneral-ized spike waves (29,30) The clinical tendency

toward epilepsy has genetic contributors as well, but these are more complex

than the inheritance of the EEG trait Although the concordance rate for

pri-mary generalized epilepsy in twin studies are high (31), the recurrence risks in

first-degree relatives of patients with primary generalized epilepsies are much

lower than the truly familial epilepsies with monogenic transmission (32)

This argues for a more complex polygenic or oligogenic mode of inheritance

A wide variety of epilepsies are seen and the prognosis is generally very

favorable, although some will require treatment for prolonged periods

As-sociated epilepsies include myoclonic epilepsy in infancy (MEI), childhood

absence epilepsy (CAE), epilepsy with myoclonic-atonic seizures (EMA) (as

described by Doose), epilepsy with myoclonic absence, epilepsy with eyelid

Pediatric ePilePsy syndromes

288

Figure 10.3: myoclonic-atonic epilepsy as described by doose this

tracing was obtained in a 4-year-old and was punctuated by runs of rietal rhythmic theta activity that occurred when the patient was clearly not drowsy.

bipa-Figure 10.2: Benign myoclonic epilepsy of infancy this infant had

re-peated myoclonic jerks associated with this burst of generalized wave activity Generalized spike waves are very rarely seen in infants, and this is one notable exception.

Figure 10.4: doose syndrome A: this youngster had a myoclonic-atonic

seizure accompanied by this eeG correlate note the burst of

general-ized polyspike activity is followed by a brief epoch of relative

attenu-ation B: a 4-year-old with doose syndrome had a clonic-tonic-clonic

seizure, which is the typical type of convulsive event note the rhythmic

spike waves at the start of this page corresponding to the clonic phase

of the seizure, which give way to the more rapid ictal discharges

corre-sponding with the transition to the vibratory tonic phase.

B

Pediatric ePilePsy syndromes

290

Figure 10.5: cae this 8-year-old child has associated oirda.

Epilepsy with Myoclonic Absences

Epilepsy with myoclonic absences is a rare form of genetic generalized lepsy (39) It may occur at any time in infancy to adolescence, with a peak in the early school-age child, usually around 7 years (40) Myoclonic absences are characterized by tonic elevation of the arms, with repeated myoclonia of the shoulders, arms, and legs The events may be asymmetric or even uni-lateral with resultant head deviation Approximately two-thirds of children will also have tonic-clonic seizures

epi-The interictal EEG is normal at onset and about half of the cases show brief generalized spike-slow-wave discharges, sometimes with fragmen-tation The ictal EEG shows rhythmic 3-Hz generalized polyspike-wave discharges (Fig 10.7)

Juvenile Absence Epilepsy

JAE and JME are both discussed in the chapter on adult epilepsy and are therefore only briefly mentioned here for completeness This epilepsy has a peak onset between 9 and 13 years of age and most often absence attacks precede myoclonic jerks and generalized tonic-clonic seizures The prognosis

is not as favorable as CAE (41)

Childhood Absence Epilepsy

CAE generally begins between 2 and 10 years of age, with a peak in the early

school-age years From the very early observations of this form of epilepsy,

it was appreciated that absences are usually frequent, with scores to

hun-dreds of seizures in a day This gave rise to the name pyknolepsy, signifying

many seizures (35) Each individual seizure is typically brief, usually less

than 10 seconds The clinical onset and offset is abrupt, with brief

impair-ment of consciousness associated with unresponsiveness and interruption

of the ongoing activity Some rhythmic eyeblinking may occur, but more

pronounced myoclonus of the face or other body parts suggests a myoclonic

form of epilepsy

The interictal EEG is normal except that rhythmic delta activity may be

seen (Fig 10.5) The attacks are accompanied by bursts of generalized 3-Hz

SWDs These often have a frontal predominance and may have up to two

spikes per complex The frequency may slow slightly as the ictal discharge

continues Typical absence attacks often begin and end with rhythmic

slow-ing with a more restricted topography (Fig 10.6) Seizures are easily

acti-vated by hyperventilation, and are more frequent with lower blood glucose

levels (36,37) Ethosuximide is the most effective medication with the least

side effects (38)

Figure 10.6: A: cae the classic 3-Hz sWd is evident this was

asso-ciated with unresponsiveness, confirming that it was a clinical absence

attack B: same ictal discharge displayed with a longer page duration

to reveal the whole discharge note how the first few discharges and

last discharges are different than the main ictal pattern (dr solomon

moshé—personal comments.)

A

B

Pediatric ePilePsy syndromes

292

Figure 10.7: myoclonic absence this 6-year-old had an absence with

repeated subtle head nods and arm myoclonia note the slight stiffening

of the arm evident in the deltoid recording there is an accompanying burst of generalized spike-wave activity.

Figure 10.8: Jae Bursts of generalized sWds are present.

The interictal EEG background is normal, upon which are superimposed

fragments of diffuse spikes and polyspikes During absence attacks, there

are 3- to 4-Hz generalized polyspike-wave discharges (Fig 10.8)

Juvenile Myoclonic Epilepsy

The history of JME has been recently reviewed (42) In 1957, Janz and

Christian (43) established the essential components of JME and paid tribute

to Herpin’s work dating back to 1867 with the name “Impulsiv Petit Mal.” JME is characterized by mild myoclonic, generalized clonic-tonic-clonic sei-zures, and absence seizures Delgado-Escueta and Greenberg (44) searched for the genetic cause and in doing so highlighted the importance of this syn-drome in the United States Onset is typically in adolescence, with myoclonic seizures The myoclonic seizures are usually bilateral but mild to moderate,

in the sense that they may cause objects to drop but usually do not result in falls They typically occur after awakening and may precede or lead directly

into a convulsion Seizures are aggravated by fatigue, sleep deprivation, or

alcohol Myoclonus may occur with brief absences, and myoclonic status

epilepticus has been described If untreated, generalized clonic-tonic-clonic

seizures are frequent

The interictal EEG in JME shows a normal background that is

punctu-ated by bursts of fast generalized spike- or polyspike-wave activity with a

repetition rate between 3.5- and 6-HZ spike (Fig 10.9) During myoclonic

seizures, there are 10- to 16-Hz rapid spikes with slow waves

Photosensi-tivity is common Like many generalized epilepsies, fragmentation of the

epileptiform discharges including clearly focal spikes can occur while awake

or asleep (45)

JME, similar to JAE, may require life-long treatment (46) The calcium

channel, voltage-dependent beta-4 subunit (2q24), chloride channel 2

(3q26), GABA1RA (5q34), GABAR delta (1p36), and the EF-hand domain

(C-terminal)-containing 1 (6p12-11) have been associated with JME

Masquerading Conditions

There are some conditions that will produce fairly well-formed generalized

spikes, but usually on an abnormal interictal EEG background Examples

of this include GLUT-1 DS (Fig 10.10), hyperinsulinemia with

hyperam-monemia (Fig 10.11), and various forms of progressive myoclonus

epi-lepsy (Fig 10.12) PME (e.g EPM1, EPM2, mitochondrial cytopathies,

and neuronal ceroid lipofuscionses) The background slowing and clinical

histories will usually allow for easy separation of these cases, but not ways Some cases may escape detection, and therefore, the differential di-agnosis should be kept broad in cases that do not show a good response to initial treatment

al-SELF-LIMITED EPILEPSIES WITH FOCAL SPIKES

The epilepsies in this second group show two common features: they have normal interictal backgrounds and they contain highly stereotyped spikes These may be found in a single focus, in homologous regions, or in multiple foci In some circumstances, the multifocal spikes may appear almost simul-taneously These have been referred to as “clone-like” and they appear to be driven by a primary spike generator, which is posterior located and often of the smallest amplitude (47)

It is not difficult to find the spikes and they nearly always enhance with drowsiness and sleep Importantly, the epileptiform activity evident in sleep

is identical to the activity while awake On some occasions, the epileptiform discharges can be elicited by special maneuvers such as temporary loss of visual fixation or finger pulp tapping There is a general pattern for the spikes to be more posterior in the younger child and to “move” more an-teriorly with age This was described by Gibbs et al (48) and referred to as

Pediatric ePilePsy syndromes

294

Figure 10.10: GlUt-1 ds this 12-year-old child has bursts of generalized

sWds with a 3-Hz repetition rate note the slight irregular nature of the spike waves and the variability of the waveforms.

Figure 10.11: Hyperinsulinemia and hyperammonemia (HiHa) this

5-month-old has bursts of spikes that are posteriorly dominant, but mately will become generalized sWds, similar to those seen in GlUt-1 ds—two conditions where the brain is not receiving adequate supply of glucose.

ulti-spikes (BECTS) or RE, and late-onset occipital epilepsy (Gastaut type) (53) There is no described neonatal form of these epilepsies.

The spectrum of these disorders is undoubtedly larger than these described syndromes We have seen children in clinical practice who have self-limited epilepsies with stereotyped spikes in other locations, including the frontal and parietal lobes, but these have not been as well character-ized in the literature and apparently are not widely recognized In addition, there can be very severe forms of almost any epilepsy, and atypical benign partial epilepsy is one such example for this group Many highly regarded authorities also consider Landau-Kleffner syndrome and continuous spike-and-wave during sleep (CSWS) as extreme versions of these same disorders, though in 25 years of clinical practice, this author has not seen a single case transform from ordinary RE to Landau-Kleffner syndrome (LKS)

well-Imaging is not required for children with RE, and probably is senseless

in those with multifocal stereotyped spikes, a normal background, normal neurological examination, and concordant history for a self-limited epilepsy The challenging cases are those children with unifocal occipital or frontal stereotyped spikes Here, it may be prudent to image to exclude the possibil-ity of an underlying focal structural lesion, even if focal slowing and attenu-ation are not present

Most children with SEFS will not require referral to a tertiary center, suming the correct diagnosis is secured Prophylactic treatment is generally

as-Panayiotopoulos uses the apt term “Benign Childhood Seizure Susceptibility

Syndrome” or BCSSS for these conditions They almost invariably have

excel-lent outcome with regard to the cessation of seizures but may be associated

with learning, behavior, or attention issues that cause havoc if not properly

recognized and treated For this reason, one might substitute “self-limited” for

“benign.” Some prefer the term “epilepsy” to “seizure syndrome,” which yields

a shorter term: Self-Limited Epilepsies with Focal Stereotyped Spikes (SEFS).

The genetics of the EEG trait for the prototype of this category— rolandic

epilepsy (RE)—have been well worked out: spikes are inherited in an

au-tosomal dominant fashion with variable penetrance according to age (49)

A similar conclusion was reached with late-onset occipital epilepsy (50) The

clinical predisposition to epilepsy, however, appears to have a relatively small

genetic component as substantiated by an analysis of several twin registries

(51) Based on this and other information, it has been estimated that the

genetic contribution to the clinical susceptibility is small and certainly not

confined to just the transmission of the EEG trait (51) This is the second

EEG-epilepsy paradox: while centrotemporal spikes are seen in all

individu-als with RE and this trait has a genetic component, the trait alone cannot

explain the genetic contribution and, moreover, the genetic contribution to

the clinical susceptibility for epilepsy appears to be small (52)

Well-described self-limited epilepsies with stereotyped focal spikes include

Panayiotopoulos syndrome (PS), benign epilepsy with centrotemporal

Figure 10.12: Progressive myoclonus epilepsy this 16-year-old girl

has ePm1 and her eeG shows bursts of generalized polyspike-wave

discharges these were often associated with myoclonia, but also

occurred independently.

Pediatric ePilePsy syndromes

296

Figure 10.13: Ps note the abundant stereotyped occipital spikes in this

recording performed on a 4 year old.

avoided, unless seizures are particularly bothersome and recurrent, but in

those children with prolonged seizures like PS, it would be wise to provide

detailed instructions for an emergency plan, including administration of a

rescue benzodiazepine for prolonged seizures

Panayiotopoulos Syndrome

PS is a childhood susceptibility to focal, mainly autonomic, seizures Children

have normal physical and neuropsychological development, and peak age of

onset is at 4 to 5 years of age, with a range from 1 to 14 years The

preva-lence is about 13% among children, with a seizure onset between ages 3 and

6 years, and overall, about 0.2% to 0.3% of the general population of

chil-dren may be affected This figure may be much higher if chilchil-dren with

atypi-cal and inconspicuous presentation are included The autonomic seizures

consist of pallor, nausea, retching, and vomiting There may be associated

papillary changes and incontinence Cardiac, breathing, and

thermoregu-latory alterations may occur Cyanosis is seen, and in some severe cases,

cardiac asystole has been reported (54) Most seizures are nocturnal Many

parents describe eye deviation and listlessness, but the seizures may end with

hemiconvulsions or a Jacksonian march Autonomic status epilepticus may

occur, and very rarely, there may be an evolution to convulsive status ticus After the postictal period resolves, the child is perfectly normal There has been one report of an association with SCN1A mutation, but this find-ing was not reproduced in another family (55,56)

epilep-Neuroimaging is likewise normal In contrast, the EEG is very useful; 90% of EEGs show multifocal stereotyped spikes and spike waves with posterior accentuation (Fig 10.13) In follow-up EEGs, 17% had a shift

of epileptiform activity from the occipital to centrotemporal areas and 3%

to frontal areas (57) In PS, frontal spikes may be activated by occipital foci (58), resulting in the synchronous occipital and frontopolar spike phe-nomenon (59) (Fig 10.14) The ictal EEG demonstrates rhythmic delta activity intermixed with small spikes Onset is unilateral and most often posterior (57)

Benign Childhood Epilepsy with Centrotemporal Spikes or Rolandic Epilepsy

Benign childhood epilepsy with centrotemporal spikes or RE is a common form of childhood epilepsy with focal motor seizures, nocturnal general-ized tonic-clonic seizures, and stereotyped centrotemporal spikes that are

Figure 10.14: Ps spikes are not restricted to the occipital region in Ps

and in this case, both independent frontal spikes and so-called Fp-o

spikes are visible.

superimposed on a normal background (60) The age range is typically 3 to

12 years, with the majority being children in the early school-age years The

epilepsy spontaneously remits in nearly all cases, with or without treatment

Diurnal seizures often involve the face and are commonly accompanied

by an inability to speak (61) Sometimes there are poorly formed

vocaliza-tions or guttural sounds Despite this, children have preserved awareness

and can often recount details of the entire event to the surprise of their

parents Professionals seldom observe nocturnal seizures, so it is difficult

to determine if these begin as focal seizures or are generalized at the onset

Spikes are distinctive (Fig 10.15) They are stereotyped, medium to high

amplitude, diphasic maximal in the midtemporal and central (C3, C4) regions

and have a horizontal dipole (62,63) Spikes are enhanced in light sleep and

they maintain their same stereotyped morphology, which can help to

distin-guish them from spikes from other etiologies They may occur on one side,

both sides independently, or bisynchronously In some patients, spikes can be

blocked by active or passive contralateral hand movements (64) Spikes may

rarely be localized to the vertex (65) Parietal spikes may also be seen in some

children in response to tactile stimulation, and this may be another useful

clinical neurophysiological feature in children with RE (66,67)

Late-Onset Occipital Lobe Epilepsy

This variant of occipital epilepsy was first described by Gastaut (68), and fore, is oftentimes referred to by that name There are several distinguishing features that allow it to be separated from PS Late-onset occipital lobe epilepsy occurs in children and adolescents, and there does not appear to be any per-sistence into adult life Seizures often begin with visual symptoms (amaurosis, phosphenes, or figurative hallucinations), which may be followed by hemiclonic attacks and other focal manifestations Migraines often follow the seizure.The EEG shows very characteristic findings (Fig 10.16) There are fre-quent runs of occipital rhythmic high-voltage spike and SWDs, which may recur at 1.5 to 3 Hz These may predominate on one side or the other, are maximally expressed when the eyes are closed, and stop with visual fixation During a seizure, there are continuous unilateral occipital SWDs (68) In con-trast to PS, late-onset occipital lobe epilepsy does not show photosensitivity

there-Landau-Kleffner Syndrome (Acquired Epileptic Aphasia)

LKS is a rare epilepsy syndrome characterized by language regression and an abnormal EEG (69) In the classic presentation, LKS presents in a

Pediatric ePilePsy syndromes

298

A

Figure 10.15: A: there are abundant stereotyped centrotemporal

spikes evident in sleep B: these spikes have a horizontal dipole evident

on the referential montage.

B

Conditions Masquerading as Self-limited Epilepsies with Focal Stereotyped Spikes

Boys with Fragile X syndrome may also demonstrate monomorphic central spikes, although this may be less than 10% of all patients (70) Central spikes may also be seen in girls with Rett syndrome and these spikes may block with limb movements (64) In both Fragile X syndrome and Rett syndrome, the EEG background will often demonstrate slowing, and certainly the clin-ical features of both conditions are very different from those individuals with RE, so the practical distinction is not a difficult one This observa-tion has been used to support an inherent predisposition to seizures in these conditions rather than structural lesions (64)

EPILEPSIES WITH ENCEPHALOPATHY (EPILEPSIES WITH SLOWED BACKGROUNDS AND MULTIFOCAL

PLEOMORPHIC SPIKES)

In most epilepsies associated with an encephalopathy, the EEG ground reveals etiologically nonspecific abnormalities Hundreds of different causes can produce the same EEG appearance, and the EEGs usually share these common features: diffuse background slowing with pleomorphic multifocal epileptiform discharges Beyond the first year of life, many will also show diffuse spikes or polyspikes that are variable in

back-Figure 10.16: late-onset occipital epilepsy (Gastaut) this 8-year-old

has prominent occipital spikes on either side (arrows) and also some

nearly simultaneous frontal spikes in association with the occipital spikes

(arrow head), so-called Fp-o spikes.

previously normal child older than 4 years, with apparent word deafness or

“verbal auditory agnosia.” Seizures and behavior disturbances, particularly

hyperactivity, are common features Many well-respected epileptologists

consider LKS to be the most extreme end of a spectrum of the self-limited

epilepsies with focal EEG features In the author’s experience, it is very rare

to see LKS developing in this context Instead, many appear to have some

preexisting abnormality and, therefore, neuroimaging is needed

The term LKS variant refers to children without the classic features

These include children with involvement of anterior language areas with

concurrent expressive aphasias or oral-motor apraxia, sialorrhea, seizures,

and an abnormal EEG (stereotyped centrotemporal spikes) There are other

children who present with pervasive developmental disorder (autism) with

language regression and abnormal EEGs Finally, there is another group

of children with developmental language disorders and epileptiform EEGs

The EEG in LKS shows bilateral, multifocal spikes and spike-and-wave

discharges, occurring usually in the posterior regions, especially the

tempo-ral region, with a marked activation during sleep A careful review of the

EEGs in the author’s personal experience and published cases often shows

admixed focal slowing This feature is common and suggests the presence

of an underlying focal structural lesion IEDs may occur in many locations,

and may even be generalized Some centers require electrical status

epilep-ticus of slow-wave sleep to diagnose LKS, but at a minimum, most would

require some degree of sleep activation of the epileptiform discharges to

make the diagnosis

Pediatric ePilePsy syndromes

300

reflective of the underlying pathophysiology, but for the time being we must await a better characterization of this complex group of patients It is frus-trating work for even the most skilled pediatric electroencephalographers because the EEGs by themselves seldom suggest a specific diagnosis (Notable exceptions to this would be ring chromosome 20, malignant migrating focal seizures of infancy, and Angelman syndrome.) Usually, it

is the details of the clinical presentation that suggest the underlying cause (e.g., Dravet disease, epilepsy in females with mental retardation, etc.)

6 months of age) in a previously normal infant who develops prolonged generalized or unilateral febrile clonic seizures, followed by frequent afebrile convulsive seizures Subsequently, the child typically has other seizure types including myoclonic seizures, atypical absence, and eye flutter attacks There may be a family history of febrile seizures or epilepsy

The interictal EEG may initially be normal, although low-amplitude occipital polyspikes in some infants are present within the first year of life (Fig. 10.17) Multifocal spikes ensue and then generalized spikes, polyspikes, and spike-wave activity develop after the second year Most often, but not invariably, there is progressive background slowing, which does not strictly correlate with the frequency of seizures or amount of interictal epileptiform activity Photosensitivity is common and develops in the first phase of the disease

Dravet disease is usually (at least 70% to 80% of cases) associated with mutations in the SCN1A gene (72) Psychomotor retardation occurs, usu-ally beginning in the second year of life, with ataxia, interictal myoclonus, and hyperreflexia The seizures are typically treatment resistant

Malignant Migrating Focal Seizures in Infancy

Malignant migrating focal seizures in infancy is a severe condition that was first described in 1995 (73) It is characterized by nearly continuous intrac-table electrographic and electroclinical seizures involving multiple indepen-dent areas of onset, beginning in the first 6 months of life in normal infants with developmental delay Previously, the cause was elusive, but more recent reports have identified likely pathogenic KCNT1 and SCN1A mutations

in affected infants (74,75) It is quite rare, with an estimated prevalence

morphology If repetitive, these diffuse epileptiform discharges will

usu-ally have a slow repetition rate

Broadly speaking, there are two subtypes of EEGs found in children with

encephalopathy and epilepsy The first group has a continuous background

and can be called the epileptogenic encephalopathies, meaning that the same

factor or factors that produced the encephalopathy also caused the epilepsy

The second group shows some element of discontinuity, often with admixed

electrodecrements, and can be termed the epileptic encephalopathies

signi-fying that the epilepsy per se may be contributing to the encephalopathy

Ex-amples of the latter include early infantile epileptic encephalopathy (EIEE),

West syndrome (WS), late infantile epileptic encephalopathy (LIEE), and

Lennox-Gastaut syndrome (LGS)

There may be various contributions of genetic, metabolic, and structural

causes in each individual When genetic, though, some general rules apply

It is rare to find a familial predisposition to either the EEG features or the

epilepsy per se in these patients There are important genetic causes of the

encephalopathies, but for the most part, they are de novo mutations, and far

less frequently, diseases caused by recessive inheritance Standard autosomal

dominant inheritance is very rare Whole-exome scanning has led to the

dis-covery of more patients with oligogenic causes, meaning that two or more

gene mutations are conspiring to produce the precise phenotype In the case

of many epileptogenic encephalopathies, it is difficult to define a precise

epi-lepsy syndrome, but perhaps further work will lead to the discovery of new

electroclinical syndromes within this group

Epileptogenic Encephalopathies

The interictal EEG of patients with epileptogenic encephalopathies shows

diffuse background slowing with superimposed multifocal pleomorphic

spikes Diffuse spikes may also occur, but these will not appear uniform and

will vary in morphology from one complex to the next Background

volt-ages, even in infancy, are below 300 μV If severe, the backgrounds may lack

an anterior to posterior voltage, and frequency gradient and sleep

architec-ture may be disrupted In contrast to the true epileptic encephalopathies,

the backgrounds tend to be continuous and electrodecrements are not a

frequent feature

There are few well-recognized syndromes in this category, and one could

argue that this grouping contains a collection of specific diseases rather than

a list of epilepsy syndromes It is entirely possible, however, that new

electro-clinical syndromes will be described as work advances, linking new genetic

discoveries with the clinical presentation Some broad themes may emerge,

Figure 10.17: infant with dravet syndrome spikes and polyspikes,

often, first become apparent in the posterior head regions later in life,

diffuse spike waves will be found.

of 0.11 per 100,000 (76) Most seizures are focal and are accompanied by

autonomic manifestations or subtle version; many have motor

manifesta-tions that migrate from one side of the body to the other The outcome is

very unfavorable: during short-term follow-up, 3 of 14 patients described by

Coppola and colleagues (73) died, although there may be a wider clinical

spectrum of this disorder (77) Treatment is difficult, but there may be some

response to bromides, stiripentol with clonazepam, and levetiracetam (78)

The interictal EEG may be normal at the very onset but quickly becomes

abnormal in all cases with multifocal spikes and sleep abnormalities The ictal

EEG is characterized by monomorphic rhythmic theta or alpha activity

pro-gressively involving multiple sites, moving from one area to another (thus the

term migrating) (Fig 10.18) Additional seizures start in other areas without

any clear relationship to the original ongoing ictus so that the seizures do not

appear to simply spread to other regions, but to arise independently

Epileptic Encephalopathies

As mentioned earlier, there is a second subgroup of epilepsies with

encephalop-athy where the EEGs show some degree of discontinuity, manifested as a

dis-continuous background, with electrodecrements, or both The most important

reason to recognize this group is the possibility that the epilepsy, per se, can

contribute to the encephalopathy, and therefore, these conditions have urgent treatment implications These may rightfully be considered epileptic encepha-lopathies Ohtahara conceptualized a spectrum with age- related differences in clinical and EEG manifestations, but a common thread consisting of severe EEG findings, epileptic encephalopathy, and refractory seizures including tonic spasms (79) Examples include the early epileptic encephalopathies (including early myoclonic encephalopathy [EME] and EIEE), WS, LIEE, and LGS The additional importance of the electrodecrements is that they indicate a suscep-tibility to epileptic spasms, myoclonic-tonic, and generalized tonic seizures— seizure types that do not respond well to conventional antiseizure agents

Background Slowing and Disorganization Are Important Parts of the Epileptic Encephalopathy

What causes the epileptic encephalopathy? It is possible that IEDs momentarily impair the brain’s ability to respond with agility (80), but the most conspicuous feature of the EEGs in the patients is the background slowing and disorganiza-tion In many different experimental settings, memory has been tied to brain oscillations, and so it stands to reason that slowing of these rhythms would have a devastating effect on cognition (81) This association of slowing with

Pediatric ePilePsy syndromes

302

Figure 10.18: migrating focal (partial) seizures in infancy A: an ictal

discharge is seen involving the right temporal lobe; B: moments later,

there is an involvement of the left temporal region.

A

B

cognitive impairment has been well known to the clinical EEGer, but perhaps

has been misinterpreted as simply a marker of brain dysfunction rather than

a potent contributor to that dysfunction More research on epileptic

encepha-lopathies will hopefully provide additional clues to the cause of these

devas-tating effects and may provide novel therapeutic approaches where defects in

learning can be targeted independent of interictal spikes and seizures (82)

Early Epileptic Encephalopathies

Two well-recognized neonatal epileptic encephalopathies are EME and EIEE EME is quite rare and characterized by fragmentary or erratic partial

myoclonus, massive body myoclonus, focal motor seizures, and tonic spasms

(83) Massive myoclonus is not invariant and tonic spasms resembling tile spasms usually appear around 3 months of age Babies show a marked

infan-encephalopathy with altered alertness, hypotonia, and hyperreflexia

Neuro-imaging is usually unremarkable The classic association is with nonketotic

hyperglycinemia, though other progressive metabolic and

neurodegenera-tive disorders must be considered The prognosis is very poor and many

patients do not survive infancy

Portions of the EEG background show burst suppression, but unlike Ohtahara syndrome, this pattern may only be seen in sleep (Fig 10.19) There are abundant multifocal spikes scattered throughout the background Although the bursts are synchronous, the spikes themselves show no bilateral synchrony beyond the random chance of coinciding over the two hemispheres

A

Figure 10.19: early myoclonic encephalopathy this infant has nonketotic

hyperglycinemia A: massive myoclonias were noted with these busts

note the burst-suppression pattern B: in another portion of the tracing

with the infant more alert, the background is slightly more continuous

this variability in the burst-suppression intervals differentiates the eeG

from that seen in ohtahara syndrome.

B

Pediatric ePilePsy syndromes

304

Figure 10.20: eiee note the characteristic burst-suppression pattern.

A similar but distinct syndrome was described by Ohtahara and

col-leagues (84) and bears his name; it is also known as early infantile

epilep-tic encephalopathy (EIEE) It is also rare, but more common than EME

(in our experience) and characterized by tonic spasms in the first month

of life and an interictal EEG showing burst suppression (85) In contrast

to EME, the burst-suppression pattern occurs in both awake and asleep,

and the interburst interval tends to be relatively constant, often about 3 to

5  seconds (Fig 10.20) The prognosis is extremely poor, with a mortality

of 50% before the age of 1 month Ohtahara syndrome has been

associ-ated with a de novo mutation in the gene encoding STXBP1 (also known as

MUNC 18 -1), a protein essential for synaptic vesicle release, as well as with

the ARX mutation (86)

Transition into WS and LGS is common in the Ohtahara syndrome and

rare in EME (87)

West Syndrome

WS is characterized by the triad of infantile spasms, hypsarhythmia, and

developmental delay The peak onset is between 4 and 7 months and always

before 12 months of age Infantile spasms are a subset of epileptic spasms

that manifest in infancy (1,88) The spasms themselves consist of sudden myoclonic and tonic phases, including brief head nods, with quick extension and flexion movements of the trunk, arms, and legs, occurring in clusters and especially during transitions from sleeping to waking

The classic interictal EEG finding, hypsarhythmia (89) was coined by Gibbs and Gibbs It is derived from the Greek word hypselos, which means “high,”

indicating the magnitude of the voltage that generally

predominates—usu-ally above 300 μV (Special note: the Gibbs’ used one “r” in hypsarhythmia

and we follow the same spelling to honor their description of the term.) In the classic form, bursts of very high-voltage slow waves occur in an irregular fashion, superimposed on a completely disorganized background with no anterior to posterior voltage/frequency gradient There are abundant multi-focal and diffuse epileptiform discharges, which often have a posterior pre-dominance (Fig 10.21) The interictal epileptiform activity may consist of spikes, sharp waves, repetitive spikes, polyspikes, and paroxysmal fast activ-ity The findings usually increase in sleep and therefore a sleep recording is very helpful in the evaluation of infants with suspected spasms (90) From time to time, and particularly in sleep, the background may suddenly be in-terrupted by a generalized electrodecrement, or less commonly in only a few EEG channels or over one hemisphere

Likewise, the ictal EEG, occurring at the time of the actual infantile

spasms may be variable, but usually has an electrodecremental response,

lasting for several seconds (Fig 10.22) There are four different components

to an electrodecrement: (a) a high-amplitude diffuse but vertex-maximal

positive slow wave (the most common element) (91); (b) Admixed multifocal

IEDs “riding” on this underlying slow wave; (c) Diffuse attenuation of the

background lasting one to several seconds; (d) Low-voltage fast rhythms

often with a posterior predominance

Hypsarhythmia variants have been described and it is important to know that they exist, but the prognosis does not appear to correlate with any of these different patterns: increased interhemispheric synchronization, asymmetrical hypsarhythmia, hypsarhythmia with a consistent focus of abnormal discharge, hypsarhythmia with episodes of attenuation, and hypsarhythmia comprising primarily high-voltage slow activity with little sharp-wave or spike activity (85)

A large number of conditions can cause WS In addition to anatomic lesions, other disorders, especially metabolic and infectious, and now, an

Figure 10.21: Ws Hypsarhythmia is a high-voltage, disorganized

pattern with multifocal spikes.

Figure 10.22: Ws the eeG correlate of an infantile spasm is an

electro-decrement note the rhomboid shape discharge on the deltoid channel

this is the common polygraphic correlate of an infantile spasm Polygraphic

channels are very useful to quickly identify whether electrodecrements

have an associate clinical component.

Pediatric ePilePsy syndromes

306

Figure 10.23: liee the background in liee is not as high voltage as in

hypsarhythmia, and there is typically more organization still, phic multifocal spikes are seen.

pleomor-expanding list of specific genetic disorders, need to be excluded (92) It is

important to note that apparently generalized spasms may stem from focal

lesions, such as tumor, stroke, or a focal cortical dysplasia (93) Practice

parameters and consensus statements have stressed the importance of

ACTH and vigabatrin over other treatments (94,95) A UK study showed

that ACTH and oral prednisone have a better efficacy than vigabatrin (96)

Vigabatrin may be especially effective when spasms are caused by tuberous

sclerosis (97) Modern protocols have resulted in a higher rate of patients

that have been successfully treated, but developmental regression remains a

persistent problem (98)

In addition to cessation of spasms, the other goal of treatment is

normal-ization or improvement of the EEG In most cases, the EEG shows rapid

im-provement when treatment is effective Complete normalization may occur

and is the most gratifying response Normalization may be only temporary,

and if abnormalities return, one must be on guard not only for the return of

spasms but also for the potential of other seizure types to develop In cases

with a poor therapeutic response and especially in those with preexisting brain

damage, a transition to LIEE or LGS a transition to LIEE or LGS may occur

Late Infantile Epileptic Encephalopathy

Some infants develop or manifest epileptic spasms or seizures closely

resem-bling spasms beyond the first year of life This entity has been recognized

for many years and has gone by several names, including cryptogenic onset epileptic spasms, infantile epileptic encephalopathy with late-onset spasms or LIEE (99–101) Myoclonic-tonic seizures are commonly seen, and resemble something between an epileptic spasm and a diffuse tonic seizure There is a sudden myoclonic movement often involving the arms, head and trunk, followed by several seconds of tonic stiffening of the same body parts The tonic phase does not last as long as a typical generalized tonic seizure, and yet has a duration longer than the typical infantile spasm Similarly, polygraphic recordings show an intermediate signature between the rhomboid shape of an epileptic spasm and the prolonged rectangular shape of a tonic seizure Spasms or myoclonic-tonic seizures can occur sin-gly, but sometimes occur in groupings with irregular time intervals between each individual spasm This is in contrast to infantile spasms or periodic spasms in older children where the time interval between spasms is rather regular

late-The interictal EEG shows slowing, multifocal spikes and a moderately high-voltage background, but usually not above 300 μV (Fig 10.23) During spasms or myoclonic-tonic seizures, there are electrodecremental responses lasting several seconds (Fig 10.24) The seizures are refractory to many different treatments and the prognosis is severe with developmental delay

in the vast majority A number of infants will go on to LGS (101) Like its counterparts, EIEE, WS, and LGS, this condition is another epileptic encephalopathy with age-related EEG and clinical manifestations

Lennox-Gastaut Syndrome

LGS is another triad of intellectual disability, mixed seizures including

particularly nocturnal tonic seizures, and diffuse slow SWDs The

proto-typic seizure is nocturnal generalized tonic, but aproto-typical absence is also

very common Drop attacks or astatic seizures consisting either of tonic

or atonic components are another common feature and are troublesome

because they can lead to substantial injury Focal seizures also occur

While Gibbs and colleagues first noted a severe prognosis in patients with

slow spike-wave complexes (the so-called “petit mal variant”), in 1939 a

detailed account of the clinical and EEG features of these patients was

given by Lennox in 1960 and Gastaut in 1966 Niedermeyer (102)

pro-posed the term Lennox-Gastaut Syndrome in 1968 and followed this with a

review years later

The interictal background is slowed and often lacks the normal

organiza-tion A well-developed and maintained posterior dominant rhythm may be

absent and there are abundant superimposed pleomorphic multifocal IEDs

Many have to come to associate the slow spike-and-wave discharge (1.5 to

2.5 Hz) as being the hallmark of LGS, but bursts of slow spike-wave

activ-ity are also seen in other conditions (Fig 10.25) Paroxysmal bursts of fast

rhythms (10 Hz) are common and typically occur during the tonic seizure

(Fig 10.26)

Just as in the other epileptic encephalopathies, there are many different potential causes of LGS Despite modern imaging, genetic evaluations and metabolic testing there are still some cases where the etiology is unknown, but probably no one develops LGS on the backdrop of completely normal development—instead there is almost invariably a history of antecedent neurological abnormalities and developmental delay LGS usually starts be-tween the ages of 1 and 10 years, and about 10% to 20% of children with LGS have passed through WS before LGS becomes evident (103)

Gastaut and colleagues (104) divided tonic seizures into axial, zomelic, and global forms All seizures are relatively short, lasting 5 to

axorhi-20  seconds With axial seizures, there is eye opening and some axial stiffness Axorhizomelic seizures have additional involvement of the proximal limbs, and global forms show diffuse involvement Tonic seizures are common in non-REM sleep and have bilateral synchronous fast or moderately fast spike activity of about 10 to 25 Hz of medium to high voltage and frontal accen-tuation is the EEG concomitant of these attacks (“runs of rapid spikes”) Electrodecrements may also occur

In atypical absence seizure, the clinical onset and termination are less abrupt than in classical absences and are usually accompanied by diffuse SWDs with a 2.5-Hz or slower repetition rate Atypical absence status epilepticus may occur Astatic seizures are often accompanied by an electrodecrement

Figure 10.24: liee a common seizure is myoclonic-tonic, which is often

associated with an abrupt relative attenuation of the background

fol-lowing a diffuse slow-wave transient (resembling, but different from a

typical electrodecremental response) the polygraphic channel shows

the myoclonic and tonic components.

Pediatric ePilePsy syndromes

308

Figure 10.25: lGs this segment of eeG shows abundant slow

spike-wave activity.

Figure 10.26: lGs commonly seen are runs of rhythmic faster

frequen-cies, which may be associated with tonic seizures in sleep this tonic seizure was axorhizomelic.

FOCAL STRUCTURAL EPILEPSIES

A common cause of refractory focal seizures in children is a focal

struc-tural lesion involving the cortical grey mantle, and one of the commonest

lesions seen at epilepsy surgery is a cortical malformation Low-grade

glio-mas and vascular lesions are other important etiologies Focal structural

lesions, regardless of their nature, are often associated with focal slowing, attenuation, or both In addition, IEDs tend to be pleomorphic with varia-tions in their precise morphology and topography This contrast with the spikes is seen in those self-limited epilepsies with focal seizures—in the lat-ter, the spikes tend to be uniform or stereotypic One way to remember this distinction is to imagine spikes arising from any of a number of locations

habitual behavior may have difficulty identifying the onset of the event The infant is unable to vocalize the presence of an aura, cannot be asked about his or her experiences during the event to determine consciousness, does not exhibit contralateral dystonic hand postures, and does not show ipsilateral fine hand automatisms Well-developed secondary generalization with syn-chronized clonic activity of both sides of the body is rare, particularly in those epilepsies with focal structural lesions (113).

The Terms, “Simple” and “Complex”

Are Difficult to Apply

It can be extraordinarily difficult to reliably determine alteration of sciousness in most infants For these reasons, the terms “simple” and “com-plex” are difficult to apply with any degree of certainty to most infantile seizures, or for that matter, any child with a preexisting issue with commu-nication With adults, it is possible to ask the patient to follow commands, repeat phrases, and to recall test items None of these can be performed in the preverbal child Inattentiveness, such as not turning the head to alerting stimuli is not the same as altered consciousness

con-As a result, Dravet and colleagues (114) studied infants with focal epilepsy

and used the term undetermined partial seizures for three patients in whom

they experienced difficulty with this assessment Duchowny (115) accepted

the term complex partial in this setting, under the assumption that some

disturbance of consciousness must have occurred, based on unsuccessful tempts to influence attention by various maneuvers In a study at The Cleve-land Clinic Foundation, of videotaped seizures from infants under 2 years old with localization-related epilepsy, the authors found it impossible to be

at-as confident about level of consciousness, despite similar attempts (116) Nordli and colleagues (105) reached the same conclusions

Infantile Focal Seizures May Have “Generalized” Clinical Features

Seizures that appear to be widespread or diffuse are common in infants but they do not necessarily have a diffuse or generalized EEG correlate Two of the most important features in this category are also diffuse tonic postures and infantile spasms Diffuse tonic postures, even symmetric ones, are com-mon during infantile focal seizures, as are other symmetric motor phenomena (117) Several authors noted bilateral tonic stiffening or clonic or myoclonic movements during focal seizures in infants (110,115)

surrounding a cortical lesion, whereas the self-limited epilepsies without

focal structural lesions have an innate driver of the spikes that reproduces

the spikes with fidelity from one instance to the other A high-quality MRI

with a careful clinical reading is of course most useful, but a considerable

amount of information about the location of the lesion can be gleaned by a

careful inspection of the interictal and ictal EEG coupled with an analysis

of the ictal semiology This allows one to focus on a particular region of the

MRI and that specificity helps to uncover subtle cortical lesions

The ictal semiology in young children has some inherent limitations as it

relates to the ability to precisely localize lesions The clinical manifestations

of seizures in infants and younger children differ markedly from those in

older children and adults; the net impact of these differences restricts our

ability to precisely localize an ictal discharge based solely on clinical features

(105,106) These differences relate, at least in part, to factors intrinsic to

the immature brain, which bestow unique electrophysiological

characteris-tics, including the underlying normal brain development, the topography of

brain metabolism, development of myelinated connections, and properties

of ion channels and their associated ion gradients

As the child matures, the intrinsic properties of brain physiology change

and thereby alter the expression of seizures Gradually, seizures take on

char-acteristics seen in adults These changes occur in an orderly fashion so that

an ontogeny of ictal semiology can be described, just as one can characterize

and predict normal child development (107,108) A general understanding

of these key differences and some detailed knowledge of the electroclinical

correlation of infantile seizures allows the examiner to ask better questions

during the medical interview, aids the evaluation epilepsy surgery, and

in-creases the chances of making a correct epilepsy syndrome diagnosis

Infantile Seizures are Often Subtle

Many infantile seizures are subtle and lack declarative features seen in

adults (105,109) This is particularly true of those arising from the temporal

lobe and posterior quadrants: the infant may pause ongoing behaviors,

sud-denly stop his movement, and exhibit simplistic automatisms, like mouthing

movements (110–112) These have been referred to as behavioral arrest,

be-havioral change, or hypomotor seizures Oxygen desaturation may

accom-pany these events, and if connected to an oxygen saturation monitor, the

change in the tone of the monitor may be the first sign alerting observers

to the presence of the seizure Parents reliably and quickly detect the

pecu-liar change in the infant’s behavior, but others unfamipecu-liar with the child’s

Pediatric ePilePsy syndromes

310

Hypermotor: Another very rare infantile focal seizure is a hypermotor

sei-zure This is characterized by incessant nonpurposeful and disorganized movements Its electrographic correlate is a unilateral hemispheric onset

of rhythmic delta waves

Diffuse tonic-focal clonic: These seizures are characterized by a bilateral

symmetric tonic posture that followed or preceded unilateral or bilateral asymmetric myoclonic jerks Electrographically, these may arise from multiple regions and have variable ictal features, including rhythmic spikes, fast spike waves, and low-voltage fast activity

Spasms with focal features: This category includes spasms that are

accompa-nied by independent focal seizures and spasms that had markedly metric features, either clinical or electrographic These are commonly seen, but may require careful inspection of the clinical and EEG features

asym-in order to be appreciated

CONCLUSIONS

Most forms of pediatric epilepsy can be easily classified using clinical formation and data from the routine interictal EEG There are only five discrete clusters that provide the necessary information to triage the patient, initiate care, and provide general prognostic information (Table 10.1) One can arrive at a more detailed diagnosis by considering the age of presenta-tion and finally the predominant seizure type (Table 10.2) Not all EEGs are equally informative owing to random sampling and a variety of other fac-tors that influence the yield of the routine EEG, so repeated EEG sampling may be necessary to confidently classify Also, the passage of time is very helpful in allowing other clinical manifestations to present

in-Still, even with repeated follow-up, there will still be some children whose epilepsy cannot be precisely classified In these situations, it is most helpful

to fall back on simple principles and to consider the development of the child and the nature of the interictal EEG

The first three groupings of EEG patterns/epilepsies occur in the context

of a normally developing child with a normal EEG background for age and either no spikes or stereotyped spike morphology These children generally do well and usually do not require extensive evaluations and can likely be man-aged without special resources (Table 10.3) (There are always exceptions to every rule All infants and those children who fail to respond to the first one or two selected medications within these groups may benefit from special scrutiny

at a tertiary center.) Conversely, the fourth and fifth EEG patterns/ epilepsies occur on the backdrop of developmental delays or focal neurological defi-cits, slowed EEG backgrounds, and pleomorphic spikes These epilepsies raise

Difficulty Lateralizing Based upon Clinical Features

The ictal semiology provides fewer clues to the laterality of the seizure in

infants when compared to older children or adults This is largely due to the

paucity of declarative features such as contralateral limb dystonia,

ipsilat-eral hand automatisms, auras, and orderly secondary genipsilat-eralization Also,

the presence of diffuse postures or spasms obscures some other features and

makes it difficult to discern subtle asymmetries

Types of Infantile Focal Seizures

and Their Electroclinical Correlations

In one study, a total of 2,112 patients were reviewed and the authors found

109 distinct seizures in 77 infants (118) Overall, 13 seizure types were

identi-fied, of which 10 types were seen in patients with focal structural epilepsy

Behavioral arrest with version: These are one of most common forms of focal

seizure in infants During the seizures, infants have a prominent

behav-ioral arrest and pronounced version of the head, eyes, or both The vast

majority have a unilateral focal onset arising from the temporo-

parieto-occipital region Often involving rhythmic activity at onset More rarely,

pure behavioral arrest without version may also be seen

Focal clonic: These seizures are characterized by unilateral or bilateral

asym-metric myoclonic jerks of the limbs in all patients The electrographic onset

is focal in all patients, and more specifically anterior (frontal, central, or

frontal-central) in about three-fourths of patients Repetitive spikes were

observed in the majority of children with this seizure type, while other

patterns include low-voltage fast activity, attenuation, or rhythmic delta

Focal tonic: These seizures are characterized by a predominant asymmetric

tonic The electrographic correlate can arise from various regions, and

most often involved some type of rhythmic activity and less likely

low-voltage fast activity

Focal tonic-clonic: These seizures are less commonly seen and are

character-ized by unilateral myoclonic jerks and asymmetric tonic posturing, which

either preceded or followed the former Electrographically, these seizures

are accompanied by a rhythmic discharge at onset

Focal tonic-clonic with secondary generalization: These seizures are

uncom-mon, particularly in the very young They are characterized by an

asym-metric or symasym-metric tonic posture followed by unilateral or bilateral

asymmetric clonus The electrographic onset is a run of unilateral spikes

or rhythmic theta-alpha (RTA) pattern

Name EEG features Neonatal Infancy Childhood Adolescence

AD familial temporal lobe

2 Genetic generalized

spike-wave epilepsies

Normal background Stereotyped GSW

Childhood absence Epilepsy with myoclonic absence

Jeavons syndrome

Juvenile absence Juvenile myoclonic

3 Self-limited epilepsies

with focal spikes

Normal background Stereotyped focal and multifocal spikes

Late-onset occipital epilepsy (Gastaut) Atypical rolandic LKS

Early myoclonic epilepsy EIEE

WS

5 Focal structural

Table 10.3 Outcome of Epilepsy Syndromes Organized by Interictal EEG Characteristics

Quick referral

to specialist?

2 Genetic generalized spike-wave

epilepsies

Normal background Stereotyped GSW

Favorable, but some require long treatment No

3 Self-limited epilepsies with focal

spikes

Normal background Stereotyped focal and multifocal spikes

Epilepsy is self-limited but may still have co-morbid conditions

No 4a Epileptogenic encephalopathies Slowed background

Pleomorphic multifocal spikes

Pleomorphic multifocal spikes Some discontinuity, electrodecrements

5 Focal structural epilepsies Focal slowing/attenuation

Pleomorphic focal spikes

311

Pediatric ePilePsy syndromes

312

16 Guerrini R, Mink JW Paroxysmal disorders associated with PRRT2 mutations shake up

expectations on ion channel genes Neurology 2012;79:2086–2088.

17 Haan J, Terwindt GM, van den Maagdenberg AM, et al A review of the genetic

re-lation between migraine and epilepsy [review] Cephalalgia 2008;28(2):105–113

doi:10.1111/j.1468-2982.2007.01460.x.

18 Heron SE, Grinton BE, Kivity S, et al PRRT2 mutations cause benign familial

infan-tile epilepsy and infaninfan-tile convulsions with choreoathetosis syndrome Am J Hum Genet

2012;90:152–160.

19 Okumura A, Shimojima K, Kubota T, et al PRRT2 mutation in Japanese children

with benign infantile epilepsy Brain Dev 2013;35(7):641–646

doi:10.1016/j.brain-dev.2012.09.015 Epub November 3, 2012.

20 Specchio N, Terracciano A, Trivisano M, et al PRRT2 is mutated in familial and

non-familial benign infantile seizures Eur J Paediatr Neurol 2013;17:77–81.

21 Oldani A, Zucconi M, Asselta R, et al Autosomal dominant nocturnal frontal lobe epilepsy: a video-polysomnographic and genetic appraisal of 40 patients and delineation

of the epileptic syndrome Brain 1998;121(Pt 2):205–223.

22 Raju GP, Sarco DP, Poduri A, et al Oxcarbazepine in children with nocturnal

frontal-lobe epilepsy Pediatr Neurol 2007;37:345–349.

23 Ottman R, Risch N, Hauser WA, et al Localization of a gene for partial epilepsy to

chromosome 10q Nat Genet 1995;10:56–60.

24 Kalachikov S, Evgrafov O, Ross B, et al Mutations in LGI1 cause autosomal-dominant

partial epilepsy with auditory features Nat Genet 2002;30:335–341.

25 Winawer MR, Ottman R, Hauser WA, et al Autosomal dominant partial epilepsy with

auditory features: defining the phenotype Neurology 2000;54:2173–2176.

26 Bisulli F, Tinuper P, Avoni P, et al Idiopathic partial epilepsy with auditory features

(IPEAF): a clinical and genetic study of 53 sporadic cases Brain 2004;127:1343–1352.

27 Berkovic SF, McIntosh A, Howell RA, et al Familial temporal lobe epilepsy: a common

disorder identified in twins Ann Neurol 1996;40:227–235.

28 Morita ME, Yasuda CL, Betting LE, et al MRI and EEG as long-term seizure outcome

predictors in familial mesial temporal lobe epilepsy Neurology 2012;79:2349–2354.

29 Metrakos K, Metrakos JD Genetics of convulsive disorders, II: genetic and

electroen-cephalographic studies in centrencephalic epilepsy Neurology 1961;11:474–483.

30 Gerken H, Doose H On the genetics of EEG-anomalies in childhood 3: spikes and

waves Neuropadiatrie 1973;4:88–97.

31 Berkovic SF, Howell RA, Hay DA, et al Epilepsies in twins: genetics of the major

epi-lepsy syndromes Ann Neurol 1998;43:435–445.

32 Steinlein GK Genetics of epilepsy syndromes In: Engel J, Pedley TA, eds Epilepsy: a comprehensive textbook, 2nd ed Philadelphia, PA: Wolters Kluwer Lippincott Williams

& Wilkins, 2008:195–210.

33 Auvin S, Pandit F, De Bellecize J, et al Benign myoclonic epilepsy in infants:

electroclini-cal features and long-term follow-up of 34 patients Epilepsia 2006;47:387–393.

34 Doose H Myoclonic-astatic epilepsy Epilepsy Res Suppl 1992;6:163–168.

35 Adie WJ Pyknolepsy; a form of epilepsy in children, with a good prognosis Proc R Soc Med 1924;17:19–25.

36 Dlugos D, Shinnar S, Cnaan A, et al Pretreatment EEG in childhood absence epilepsy:

associations with attention and treatment outcome Neurology 2013;81:150–156.

37 Gibbs FA, Gibbs EL, Lennox WG Influence of the blood sugar level on the wave and

spike formation in petit mal epilepsy Arch NeurPsych 1939;41:1111–1116.

38 Glauser TA, Cnaan A, Shinnar S, et al Ethosuximide, valproic acid, and lamotrigine in

childhood absence epilepsy N Engl J Med 2010;362:790–799.

39 Tassinari CA, Lyagoubi S, Santos V, et al Study on spike and wave discharges in man,

II: clinical and electroencephalographic aspects of myoclonic absences [in French] Rev Neurol 1969;121:379–383.

more concerns and would benefit from prompt evaluations at centers with

special expertise in the management of child with epilepsy, including surgical

evaluations Patients in groups 4 and 5 require a careful review of imaging

to look not only for focal structural lesions that might be taken care of by

surgical treatment but also for clues to other causes of epilepsy In addition,

patients in group 4 can benefit from metabolic and genetic tests, particularly

in those with early onset of epilepsy The emphasis of this evaluation should

be on identifying those conditions that respond to specific treatments such as

GLUT-1 DS, pyridoxine responsive seizures, and creatine deficiency, to name

a few It is equally important to identify those specific treatments that should

be avoided such as valproate in patients with Alpers, or phenytoin in

progres-sive myoclonus epilepsies

REFERENCES

1 Berg AT, Berkovic SF, Brodie MJ, et al Revised terminology and concepts for

organiza-tion of seizures and epilepsies: report of the ILAE Commission on Classificaorganiza-tion and

Terminology, 2005–2009 Epilepsia 2010;51:676–685.

2 Helbig I, Lowenstein DH Genetics of the epilepsies: where are we and where are we

go-ing? Curr Opin Neurol 2013;26:179–185.

3 Binnie CD, Prior PF Electroencephalography J Neurol Neurosurg Psychiatry 1994;

57:1308–1319.

4 Derry CP, Heron SE, Phillips F, et al Severe autosomal dominant nocturnal frontal

lobe epilepsy associated with psychiatric disorders and intellectual disability Epilepsia

2008;49:2125–2129.

5 Plouin P, Kaminska A Neonatal seizures Handb Clin Neurol 2013;111:467–476.

6 Hirsch E, Velez A, Sellal F, et al Electroclinical signs of benign neonatal familial

convul-sions Ann Neurol 1993;34(6):835–841.

7 Aso K, Watanabe K Benign familial neonatal convulsions: generalized epilepsy? Pediatr

Neurol 1992;8(3):226–228.

8 Bye AM Neonate with benign familial neonatal convulsions: recorded generalized and

focal seizures Pediatr Neurol 1994;10(2):164–165.

9 Zara F, Specchio N, Striano P, et al Genetic testing in benign familial epilepsies of the

first year of life: clinical and diagnostic significance Epilepsia 2013;54:425–436.

10 Heron SE, Crossland KM, Andermann E, et al Sodium-channel defects in benign

fa-milial neonatal-infantile seizures Lancet 2002;360(9336):851–852 Erratum in: Lancet

2002;360(9344):1520.

11 Specchio N, Vigevano F The spectrum of benign infantile seizures [review] Epilepsy Res

2006;70(Suppl 1):S156–S167 Epub July 11, 2006.

12 Capovilla G, Vigevano F Benign idiopathic partial epilepsies in infancy [review] J Child

Neurol 2001;16(12):874–881.

13 Watanabe K, Negoro T, Aso K Benign partial epilepsy with secondarily generalized

sei-zures in infancy Epilepsia 1993;34(4):635–638.

14 Fukuyama Y Borderland of epilepsy with special reference to febrile convulsions and

so-called infantile convulsions Seishin-Igaku (Clin Psychiatry) 1963;5:211–223.

15 Bureau M, Cokar O, Maton B, et al Sleep-related, low voltage Rolandic and vertex

spikes: an EEG marker of benignity in infancy-onset focal epilepsies Epileptic Disord

2002;4:15–22.

65 Pedley TA, Tharp BR, Herman K Clinical and electroencephalographic characteristics

of midline parasagittal foci Ann Neurol 1981;9:142–149.

66 de Marco P, Tassinari CA Extreme somatosensory evoked potential (ESEP): an EEG sign

forecasting the possible occurrence of seizures in children Epilepsia 1981;22:569–575.

67 Manganotti P, Miniussi C, Santorum E, et al Influence of somatosensory input on oxysmal activity in benign rolandic epilepsy with “extreme somatosensory evoked poten-

71 Dalla Bernardina B, Capovilla G, Gattoni MB, et al Severe infant myoclonic epilepsy

[review, in French] Rev Electroencephalogr Neurophysiol Clin 1982;12(1):21–25.

72 Scheffer IE Does genotype determine phenotype? Sodium channel mutations

in Dravet syndrome and GEFS+ Neurology 2011;76(7):588–589 doi:10.1212/

WNL.0b013e31820d8b51 Epub January 19, 2011 PubMed PMID: 21248272.

73 Coppola G, Plouin P, Chiron C, et al Migrating partial seizures in infancy: a malignant

disorder with developmental arrest Epilepsia 1995;36:1017–1024.

74 Barcia G, Fleming MR, Deligniere A, et al De novo gain-of-function KCNT1 channel

mu-tations cause malignant migrating partial seizures of infancy Nat Genet 2012;44:1255–1259.

75 Freilich ER, Jones JM, Gaillard WD, et al Novel SCN1A mutation in a proband with

malignant migrating partial seizures of infancy Arch Neurol 2011;68:665–671.

76 McTague A, Appleton R, Avula S, et al Migrating partial seizures of infancy:

ex-pansion of the electroclinical, radiological and pathological disease spectrum Brain

2013;136:1578–1591.

77 Marsh E, Melamed SE, Barron T, et al Migrating partial seizures in infancy: expanding

the phenotype of a rare seizure syndrome Epilepsia 2005;46:568–572.

78 Coppola G Malignant migrating partial seizures in infancy Handb Clin Neurol

2013;111:605–609.

79 Yamatogi Y, Ohtahara S Age-dependent epileptic encephalopathy: a longitudinal study

Folia Psychiatr Neurol Jpn 1981;35:321–332.

80 Ebus S, Arends J, Hendriksen J, et al Cognitive effects of interictal epileptiform

dis-charges in children Eur J Paediatr Neurol 2012;16:697–706.

81 Hanslmayr S, Staudigl T How brain oscillations form memories—a processing based

perspective on oscillatory subsequent memory effects Neuroimage Neuroimage

2014;85(Pt 2):648–655 doi:10.1016/j.neuroimage.2013.05.121 Epub June 11, 2013

82 Chan KF, Burnham WM, Jia Z, et al GABAB receptor antagonism abolishes the

learning impairments in rats with chronic atypical absence seizures Eur J Pharmacol

2006;541:64–72.

83 Aicardi J, Goutieres F Neonatal myoclonic encephalopathy (author’s transl) [in French]

Rev Electroencephalogr Neurophysiol Clin 1978;8:99–101.

84 Ohtahara S, Ishida T, Oka E, et al On the specific age-dependent epileptic syndromes:

the early-infantile epileptic encephalopathy with suppression-burst No To Hattatsu

1976;8:270–280.

85 Hrachovy RA, Frost JD Jr, Kellaway P Hypsarrhythmia: variations on the theme sia 1984;25:317–325.

86 Deprez L, Weckhuysen S, Holmgren P, et al Clinical spectrum of early-onset epileptic

encephalopathies associated with STXBP1 mutations Neurology 2010;75:1159–1165.

87 Murakami N, Ohtsuka Y, Ohtahara S Early infantile epileptic syndromes with

suppres-sion-bursts: early myoclonic encephalopathy vs Ohtahara syndrome Jpn J Psychiatry Neurol 1993;47:197–200

40 Bureau M, Tassinari CA Epilepsy with myoclonic absences Brain Dev 2005;27:178–184.

41 Tovia E, Goldberg-Stern H, Shahar E, et al Outcome of children with juvenile absence

epilepsy J Child Neurol 2006;21:766–768.

42 Thomas P, Genton P, Gelisse P, et al Juvenile myoclonic epilepsy In: Bureau M, Genton

P, Dravet C, et al, eds Epileptic syndromes in infancy, childhood and adolescence, 5th ed

Montrouge, France: John Libbey Eurotext, 2012.

43 Janz D, Christian W Impulsiv petit mal Dtsch Z Nervenheilk 1957;176:346–386.

44 Delgado-Escueta AV, Greenberg D The search for epilepsies ideal for clinical and

mo-lecular genetic studies Ann Neurol 1984;16(Suppl):S1–S11.

45 So GM, Thiele EA, Sanger T, et al Electroencephalogram and clinical focalities in

juve-nile myoclonic epilepsy J Child Neurol 1998;13(11):541–545.

46 Camfield CS, Camfield PR Juvenile myoclonic epilepsy 25 years after seizure onset: a

popula-tion-based study Neurology 2009;73(13):1041–1045 doi:10.1212/WNL.0b013e3181b9c86f.

47 Panayiotopoulos CP Idiopathic childhood occipital epilepsies In: Roger J, Bureau M,

Dravet CH, et al, eds Epileptic syndromes in infancy, childhood, and adolescence

Eastle-ight, England: John Libbey, 2002:203–227.

48 Gibbs EL, Gillen HV, Gibbs FA Disappearance and migration of epileptic foci in

chil-dren Am J Dis Child (1960) 1954;88:596–603.

49 Bray PF, Wiser WC Evidence for a genetic etiology of temporal-central abnormalities in

focal epilepsy N Engl J Med 1964;271:926–933.

50 Kuzniecky R, Rosenblatt B Benign occipital epilepsy: a family study Epilepsia

1987;28:346–350.

51 Vadlamudi L, Kjeldsen MJ, Corey LA, et al Analyzing the etiology of benign rolandic

epilepsy: a multicenter twin collaboration Epilepsia 2006;47:550–555.

52 Doose H, Brigger-Heuer B, Neubauer B Children with focal sharp waves: clinical and

genetic aspects Epilepsia 1997;38:788–796.

53 Guerrini R, Pellacani S Benign childhood focal epilepsies Epilepsia 2012;53(Suppl 4):9–18.

54 Verrotti A, Salladini C, Trotta D, et al Ictal cardiorespiratory arrest in Panayiotopoulos

syndrome Neurology 2005;64:1816–1817.

55 Livingston JH, Cross JH, McLellan A, et al A novel inherited mutation in the voltage

sensor region of SCN1A is associated with Panayiotopoulos syndrome in siblings and

generalized epilepsy with febrile seizures plus J Child Neurol 2009;24:503–508.

56 Martin Del Valle F, Diaz Negrillo A, Ares Mateos G, et al Panayiotopoulos syndrome:

probable genetic origin, but not in SCN1A Eur J Paediatr Neurol 2011;15:155–157.

57 Specchio N, Trivisano M, Di Ciommo V, et al Panayiotopoulos syndrome: a clinical,

EEG, and neuropsychological study of 93 consecutive patients Epilepsia 2010;51(10):

2098–2107 doi:10.1111/j.1528-1167.2010.02639.x Epub September 21, 2010.

58 Leal AJ, Ferreira JC, Dias AI, et al Origin of frontal lobe spikes in the early onset

be-nign occipital lobe epilepsy (Panayiotopoulos syndrome) Clin Neurophysiol 2008;119(9):

1985–1991 doi:10.1016/j.clinph.2008.04.299 Epub July 11, 2008.

59 Yoshinaga H, Kobayashi K, Ohtsuka Y Characteristics of the synchronous occipital

and frontopolar spike phenomenon in Panayiotopoulos syndrome Brain Dev 2010;32(8):

603–608 doi:10.1016/j.braindev.2009.09.007 Epub October 7, 2009.

60 Nayrac P, Beaussart M Pre-rolandic spike-waves: a very peculiar EEG reading;

electro-clinical study of 21 cases [in French] Rev Neurol 1958;99:201–206.

61 Loiseau P, Beaussart M The seizures of benign childhood epilepsy with Rolandic

parox-ysmal discharges Epilepsia 1973;14:381–389.

62 Gregory DL, Wong PK Clinical relevance of a dipole field in rolandic spikes Epilepsia

1992;33:36–44.

63 Huiskamp G, van Der Meij W, van Huffelen A, et al High resolution spatio-temporal

EEG-MEG analysis of rolandic spikes J Clin Neurophysiol 2004;21:84–95.

64 Niedermeyer E, Naidu S Further EEG observations in children with the Rett syndrome

Brain Dev 1990;12:53–54.

Pediatric ePilePsy syndromes

314

88 Noachtar S, Binnie C, Ebersole J, et al A glossary of terms most commonly used by

clinical electroencephalographers and proposal for the report form for the EEG findings

The International Federation of Clinical Neurophysiology Electroencephalogr Clin

Neu-rophysiol Suppl 1999;52:21–41.

89 Gibbs FA, Gibbs EL Atlas of electroencephalography Cambridge, MA: Addison-Wesley,

1952:222–224.

90 Bower BD, Jeavons PM Infantile spasms and hypsarrhythmia Lancet 1959;1:605–609.

91 Fusco L, Vigevano F Ictal clinical electroencephalographic findings of spasms in West

syndrome Epilepsia 1993;34:671–678.

92 Mastrangelo M, Leuzzi V Genes of early-onset epileptic encephalopathies: from

geno-type to phenogeno-type Pediatr Neurol 2012;46:24–31.

93 Chugani HT, Shields WD, Shewmon DA, et al Infantile spasms, I: PET

identi-fies focal cortical dysgenesis in cryptogenic cases for surgical treatment Ann Neurol

1990;27:406–413.

94 Pellock JM, Hrachovy R, Shinnar S, et al Infantile spasms: a U.S consensus report

Epilepsia 2010;51:2175–2189.

95 Mackay MT, Weiss SK, Adams-Webber T, et al Practice parameter: medical treatment

of infantile spasms: report of the American Academy of Neurology and the Child

Neu-rology Society NeuNeu-rology 2004;62:1668–1681.

96 Lux AL, Edwards SW, Hancock E, et al The United Kingdom Infantile Spasms Study

(UKISS) comparing hormone treatment with vigabatrin on developmental and epilepsy

outcomes to age 14 months: a multicentre randomised trial Lancet Neurol 2005;4:712–717.

97 Chiron C, Dumas C, Jambaque I, et al Randomized trial comparing vigabatrin and

hydrocortisone in infantile spasms due to tuberous sclerosis Epilepsy Res 1997;26:389–395.

98 Bitton JY, Sauerwein HC, Weiss SK, et al A randomized controlled trial of flunarizine

as add-on therapy and effect on cognitive outcome in children with infantile spasms

Epilepsia 2012;53:1570–1576.

99 Eisermann MM, Ville D, Soufflet C, et al Cryptogenic late-onset epileptic spasms: an

overlooked syndrome of early childhood? Epilepsia 2006;47:1035–1042.

100 Nordli DR Jr, Korff CM, Goldstein J, et al Cryptogenic late-onset epileptic spasms or

late infantile epileptogenic encephalopathy? Epilepsia 2007;48:206–208.

101 Auvin S, Lamblin MD, Pandit F, et al Infantile epileptic encephalopathy with late-onset

spasms: report of 19 patients Epilepsia 2010;51:1290–1296.

102 Niedermeyer E The Lennox-Gastaut syndrome and its frontiers Clin Electroencephalogr

1986;17:117–126.

103 Niedermeyer E The Lennox-Gastaut syndrome: a severe type of childhood epilepsy

Dtsch Z Nervenheilkd 1969;195:263–282.

104 Gastaut H, Roger J, Ouahchi S, et al An electro-clinical study of generalized epileptic

seizures of tonic expression Epilepsia 1963;4:15–44.

105 Nordli DR Jr, Bazil CW, Scheuer ML, et al Recognition and classification of seizures in

infants Epilepsia 1997;38:553–560.

106 Hamer HM, Wyllie E, Luders HO, et al Symptomatology of epileptic seizures in the first

three years of life Epilepsia 1999;40:837–844.

107 Nordli DR Jr, Kuroda MM, Hirsch LJ The ontogeny of partial seizures in infants and

young children Epilepsia 2001;42:986–990.

108 Jayakar P, Duchowny M Complex partial seizures of temporal lobe origin in early

child-hood J Epilepsy 1990;3:41–45.

109 Duchowny M The syndrome of partial seizures in infancy J Child Neurol 1992;7:66–69.

110 Yamamoto N, Watanabe K, Negoro T, et al Complex partial seizures in children: ictal

manifestations and their relation to clinical course Neurology 1987;37:1379–1382.

111 Wyllie E, Chee M, Granstrom ML, et al Temporal lobe epilepsy in early childhood

Epilepsia 1993;34:859–868.

112 Karbowski K, Vassella F, Pavlincova E, et al Psychomotor seizures in infants and young

children [in German] EEG EMG Z Elektroenzephalogr Elektromyogr Verwandte Geb

115 Duchowny MS Complex partial seizures of infancy Arch Neurol 1987;44:911–914.

116 Acharya JN, Wyllie E, Luders HO, et al Seizure symptomatology in infants with

localization-related epilepsy Neurology 1997;48:189–196.

117 Brockhaus A, Elger CE Complex partial seizures of temporal lobe origin in children of

different age groups Epilepsia 1995;36:1173–1181.

118 Korff CM, Nordli DR Jr The clinical-electrographic expression of infantile seizures

Epilepsy Res 2006;70(Suppl 1):S116–S131.

Focal IEDGeneralized IEDPhoto-Epileptiform Discharges (Photoparoxysmal Response)

Ictal EEG

Features of Scalp-Recorded Ictal Discharges

Ictal EEG in Focal EpilepsyIctal EEG in Generalized Epilepsy

Limitation of Interictal and Ictal Scalp EEG Summary

References

IntRoDuctIon

The use of EEG in the evaluation of seizure disorders typically begins in the

outpatient setting as a procedure performed using scalp electrodes during the

interictal period Ictal EEG is now commonly performed with simultaneous

video recording, in either outpatient or inpatient setting The objective of this

chapter is to discuss the types of interictal epileptiform discharges (IEDs) and

ictal discharges recorded from the scalp in adults The emphasis of this chapter

is on the features of IEDs and ictal discharges and their clinical correlation

IntERIctaL EpILEptIfoRm DISchaRGES

According to the International Federation of Societies for

Elec-troencephalography and Clinical Neurophysiology, “epileptiform”

abnormalities “applies to distinctive waveforms or complexes resembling those recorded in a proportion of human subjects suffering from epi-leptic disorders and in animals rendered epileptic experimentally” (1) Another definition of epileptiform waveforms or patterns is that they are EEG abnormalities that are associated with a predisposition to experi-

encing or developing epileptic seizures The word predisposition is used

to indicate that the association between epileptiform abnormalities and seizure disorders is not absolute Presence of epileptiform discharges does not necessarily indicate that the patient has a seizure disorder (2) However, the detection of epileptiform abnormalities does increase the likelihood of an epileptic seizure disorder being present When the find-ing is taken together with the clinical history and other diagnostic test results, epileptiform abnormalities help in establishing the diagnosis of epileptic seizure disorders

EEG in Adult EpilEpsy

316

focal IED

Spikes/Sharp Waves

Spikes are transient waveforms with pointed peaks when displayed at a screen

resolution of approximately 30 mm per second (Fig 11.1) By definition,

du-ration of spikes varies from 20 to 70 milliseconds, whereas sharp waves are

wider with duration between 70 and 200 milliseconds (1) The distinction in

this regard between spikes and sharp waves is somewhat arbitrary The two

types of waves often occur in the same clinical disorder or the same patient

Spikes/sharp waves should have sufficient amplitudes to distinguish them

from the background, such as by a factor of two They are often polyphasic,

but the main component is usually surface-negative Surface-positive IEDs

are rare, and can occur at the site of craniotomy (3), particularly if lateral

convexity cortex is removed, but not more mesial cortex Central positive

sharp waves can be observed in infants with intraventricular hemorrhage or

periventricular white matter injury, but the discharges are a better indication

of encephalopathy than of epileptogenicity (4)

Spikes/sharp waves are often followed by a slow wave that can be smaller

or larger than the spike/sharp wave discharges themselves The spike/sharp wave with its after-going slow wave may be referred to as a “spike-and-slow-wave complex” (i.e., a complex is a series of two or more individual waves) The accompaniment of spikes/sharp waves by an after-going slow wave may not be constant in the same patient and at the same location When the spike/sharp wave is of negative polarity, as is most often the case, the after-coming wave will be negative as well Separating these two will be a deflec-tion of positive polarity

Focal Spikes/Sharp WavesCommon locations of focal spike/sharp-wave discharges, in the approximate order of frequency, are temporal, frontal, centrotemporal, parietal, occipi-tal, and midline central and/or paracentral The clinical correlation of focal spikes/sharp waves is with focal epilepsy; however, the likelihood that a given focal spike/sharp wave is associated with epilepsy varies with its location (5) For instance, the association is higher for temporal spikes/sharp waves than

figure 11.1: left midtemporal spike in a 33-year-old woman who had

been experiencing spells of smelling burnt rubber, followed by lip ing and behavior of confusion this spike discharge is not followed by

smack-an after-going slow wave MRi showed a cavernous smack-angioma at the left temporal lobe, despite lack of left temporal slowing during wake EEG.

with periventricular hemorrhage or leukomalacia and in young children with multifocal spikes/sharp waves, especially in the presence of global encepha-lopathy, such as with ischemic injury or lipid storage diseases (9,10).

The identification of focal spikes/sharp waves is very important in the agnosis of benign, age-related epilepsy syndromes (see Chapter 10) Spikes/sharp waves in these syndromes have distributions, morphology, and activa-tion factors that are characteristic for each syndrome The most common

di-is benign epilepsy of childhood with centrotemporal spikes (also known as benign epilepsy with centrotemporal spikes, BECT, or benign rolandic epi-lepsy) Other childhood syndromes of focal epilepsy are benign childhood epilepsy with occipital paroxysms and the syndrome of early-onset child-hood seizures with occipital spikes (Panayiotopoulos syndrome) (11).Multifocal Spikes

Multifocal spikes/sharp waves refer to the presence of multiple dent foci of spikes or sharp waves that involve both hemispheres (Fig 11.2) Although this abnormality can be seen at any age, it is most frequently observed in children aged 4 to 7 years (12) Background EEG slowing is

indepen-for rolandic or occipital spikes/sharp waves Approximately 90% of children

with anterior temporal spikes have seizures, whereas seizures are present in

only 38% of those with rolandic spikes Temporal lobe tissues, especially the

hippocampus and the amygdala, are some of the most epileptogenic The

temporal lobes are also frequently involved in pathologic conditions, such as

hypoxia, strokes, tumors, trauma, and vascular malformations In contrast,

many children with occipital IED do not have epilepsy; in fact, about 60% of

children with occipital spikes do not have epileptic seizure disorders (6), and

occipital IEDs are even encountered in nonepileptic persons with migraine

disorders (7) Other occipital discharges, known as “needle spikes,” can be

ob-served in the EEG of children who have congenital blindness but not epilepsy

(8) These occipital spikes are low in amplitude and sharp in configuration

Most focal spikes/sharp waves are surface negative at the scalp Positive

spikes/sharp waves are not common in the adult patient They can be seen

postoperatively when overlying convexity cortex is removed, but more mesial

cortex remains Synchronous, but spatially separated, positive and negative

spikes are evident when the spike voltage field is tangential rather than radial

Positive-polarity discharges are more frequently encountered in newborns

figure 11.2: Multifocal spikes appearing at F4, F8, p8, O1, and

bisyn-chronously at the occipital regions the patient had medically refractory

seizures since childhood note also the generalized slowing in the

back-ground EEG is displayed in laplacian montage the patient had other

EEG abnormalities, which, together with the clinical history, suggest lGs

(see Figs 11.7 and 11.9).

EEG in Adult EpilEpsy

318

distribution within a hemisphere, or more diffusely affecting a whole sphere The temporo-parietal-occipital region is most frequently involved PLEDs are highly associated with acute cerebral disorders, especially those producing structural lesions such as stroke (infarct or hematoma), brain trauma, herpes encephalitis, tumor, and abscess Rare causes include met-abolic encephalopathy, Creutzfeldt-Jakob disease, migraine, and toxic en-cephalopathy (e.g., aminophylline or alcohol intoxication)

hemi-Fifty percent of patients with PLEDs will develop seizures, most often

of a focal nature, with or without secondary generalization Reiher and colleagues (17) observed that PLEDs may be multiphasic and burst-like in appearance PLEDs-plus is the term they coined for this type of periodic activity, as opposed to the less complex morphology of PLEDs-proper PLEDs-plus carries a much higher association with clinical seizures and status epilepticus In fact, ictal activity is commonly recorded with PLEDs-plus

present in nearly all these patients, and 94% of them have seizures

General-ized motor seizures are the most common, occurring in 76% of patients (13)

Seizures are typically frequent, with half of the patients experiencing daily

seizures Concomitant neurological abnormalities are also common; 45%

of these patients have motor deficits and 82% have mental retardation and

developmental delay The majority (71%) have underlying structural brain

abnormalities or a history of brain injury

Periodic Lateralized Epileptiform Discharges

Periodic lateralized epileptiform discharges (PLEDs) are epileptiform

dis-charges or complexes that recur with a regular periodicity in one

hemi-sphere, usually every 0.3 to 4 seconds (14) (Fig 11.3) This periodic activity

may take the form of monophasic or polyphasic spikes or sharp waves,

which may or may not have accompanying slow waves (15,16) Although

very focal PLEDs have been observed, usually the discharges are regional in

figure 11.3: periodic lateralized epileptiform discharges (plEds) at

the right hemisphere in a 40-year-old man who had a small right frontal tumor the patient experienced a generalized convulsive seizure 12 hours before the EEG recording was performed.

Nearly 90% of patients with multifocal PLEDs have seizures Prognosis is dependent on the underlying cerebral disorder For example, patients with acute cerebral lesions or infections have a higher mortality than those whose PLEDs follow a bout of multiple seizures.

Temporal Intermittent Rhythmic Delta Activity

Temporal intermittent rhythmic delta activity (TIRDA) consists of mittent sinusoidal trains of rhythmic delta waves from the temporal region that typically last several seconds (Fig 11.4) (20,21) The most common frequency is 2 to 3 Hz Although anterior temporal is the predominant loca-tion, posterior TIRDA can also be observed TIRDA may appear in wake-fulness or sleep, but it is often most easily identified in drowsiness Reiher and colleagues (20) have demonstrated that TIRDA is highly correlated with

inter-a history of temporinter-al lobe seizures In inter-a cinter-ase-control study, inter-all pinter-atients with TIRDA were shown to have complex partial epilepsy (21), and the major-ity also had temporal spikes/sharp waves on their EEGs Temporal depth

PLEDs are transient and they may transform over days or weeks into

in-termittent monomorphic slow waves with or without sporadic spikes/sharp

waves The interval between discharges typically lengthens over time as well

These intermittent slow waves eventually disappear, possibly leaving

resid-ual focal slowing, which reflects the sequela of underlying brain damage

When PLEDs are recorded bilaterally, the term BIPLEDs is commonly

used These discharges may be temporally dependent or independent (18)

They are encountered in patients with severe hypoxic encephalopathy or

bilateral hemisphere destructive lesions BIPLEDs, particularly when

inde-pendent, are associated with a poor prognosis for survival or recovery of

normal neurological functions

In multifocal PLEDs, there are at least three foci of periodic activity

in-volving both hemispheres (19) Multifocal PLEDs are encountered in

pa-tients with severe and diffuse brain dysfunction or with multifocal lesions

of both cerebral hemispheres Etiologies include multifocal strokes,

infec-tion, a state of seizure exacerbainfec-tion, and toxic/metabolic encephalopathy

figure 11.4: temporal intermittent rhythmic delta activity (tiRdA;

indi-cated by a circle) at the right temporal lobe in a 32-year-old patient with

medically refractory epilepsy MRi showed evidence of right mesial

tem-poral sclerosis, in the form of hippocampal atrophy and fluid-attenuated

inversion recovery (FlAiR) signal abnormality.

EEG in Adult EpilEpsy

320

figure 11.5: Hyperventilation-induced paroxysm of 3-Hz

spike-and-waves in an 11-year-old girl who had behavioral arrest and eyelid ing during the paroxysm (interval between gridlines is 200 milliseconds.)

flutter-electrode recording during TIRDA on the scalp showed active spiking from

the amygdalohippocampal structures TIRDA is commonly associated with

underlying structural lesions In fact, two-thirds of the patients in the study

had pathology of the temporal lobe

Generalized IED

Generalized IEDs have a variety of forms—3-Hz spike-and-waves, atypical

spike-and-slow-waves, slow spike-and-wave discharges, hypsarhythmia, and

generalized repetitive fast discharge (GRFD)

3-Hz Spike-and-Wave

As the name implies, 3-Hz spike-and-wave discharges are runs of bilateral

spikes and after-coming slow waves that repeat rhythmically at a rate of three

cycles per second (Fig 11.5) Each burst typically lasts between 1 and

3 sec-onds, but longer runs occur, especially when activated by hyperventilation

(HV) or drowsiness These bilateral bursts are synchronous in timing and symmetric in amplitude between hemispheres, although shifting asymmetry

is common from burst to burst On close inspection, latency differences tween hemispheres can be detected, but usually by no more than 20 millisec-onds The amplitude of these discharges may be upward of several hundred microvolts and typically most prominent in the midline frontal region.3-Hz spike-and-wave discharges are the EEG signature of absence epilepsy

be-It is now known that even a brief burst can interfere with mental functioning The effect is subtle and may not be apparent by visual observation; however, neuropsychological testing has demonstrated that even a 1- or 2-second burst will briefly interrupt continuous motor tasks (22) Bursts of 3 seconds or longer duration are more consistently accompanied by the clinical signs of

an absence seizure, namely, behavioral arrest, staring, and/or eye fluttering

HV is a standard procedure for activating absence seizures and 3-Hz spike-and-wave bursts during EEG recording However, clinicians must be aware of pseudo-absence events that can occur in some children without

bursts The atypical spike-and-slow-wave pattern is more likely to occur as single bursts rather than in long repetitive runs Drowsiness and non-REM sleep activate generalized atypical spike-and-slow-wave discharges, and they may be entirely absent during wakefulness in some patients.

The clinical correlation of the generalized atypical spike-and-slow-wave abnormality is with primary generalized epilepsy, including benign myo-clonic epilepsy of early childhood, myoclonic-astatic epilepsy of early child-hood, juvenile myoclonic epilepsy (JME) of Janz, juvenile absence epilepsy, atypical absence epilepsy, epilepsy with grand mal on awakening, and pho-tosensitive epilepsy (26)

In patients with both 3-Hz and atypical spike-and-slow waves, it is not uncommon for focal spikes of low amplitude to appear during drowsiness

in the frontal or temporal regions These do not indicate an accompanying focal seizure disorder, as long as they are not abundantly present at a single location during wakefulness or sleep

epilepsy (23) This nonepileptic phenomenon has EEG features of runs of

high-voltage, semirhythmic to rhythmic, delta waves that may be slower than

the usual HV buildup This slowing is widely distributed, but often with a

maximal amplitude at the anterior head regions However, careful analysis

of the EEG in pseudo-absence spells shows that spikes are lacking, unlike

real 3-Hz spike wave Unfortunately, the clinical appearance of pseudo-

absence spells can mimic that of genuine absence seizures (24) Accordingly,

an EEG recording is required to differentiate the two

Generalized Atypical Spike-and-Slow-Waves

Generalized atypical spike-and-slow-wave discharges are bilaterally

synchro-nous complexes that resemble 3-Hz spike-and-wave discharges, but differ in

that they have variable rates, although mostly close to 4 Hz Also, the spike

component of the complexes is often polyphasic (25) (Fig 11.6) Moreover,

the complexes vary greatly in amplitude and morphology within and between

figure 11.6: Generalized atypical spike-and-slow-wave complexes in a

19-year-old woman who since age 13 years has had sporadic generalized

tonic-clonic seizures on awakening in the morning the patient did not

have myoclonic jerks or absence spells, but the recorded paroxysms,

such as the one shown in this figure, were sometimes accompanied by

brief arrest of activity.

EEG in Adult EpilEpsy

322

pattern is commonly seen as one of the EEG features of Lennox-Gastaut syndrome (LGS) in children and adults

Generalized Repetitive Fast Discharge

GRFD is also known as paroxysmal fast rhythm, generalized paroxysmal fast activity, or “runs of rapid spikes” (28,29) This pattern consists of bursts

of repetitive spikes in the alpha or beta frequency range (Fig 11.8) The bursts are generalized in distribution, typically last less than 10 seconds, and are of low to medium amplitude

Most GRFD occurs during sleep It can be considered an ictal rhythm, because tonic seizure activity sometimes accompanies it However, this tonic seizure activity may be subtle and take the form of tonic slow eye opening GRFD may also be accompanied by transient apnea or bradycardia in some children A particular type of GRFD, referred to as an electrodecrement,

Slow Spike-and-Waves (Sharp-and-Slow-Wave Complexes)

As the name indicates, the slow spike-and-wave discharge pattern is

charac-terized by complexes that occur slower than the “prototypical” 3-Hz

spike-and-wave discharge pattern of absence epilepsy (Fig 11.7), namely, around

1.0 to 2.5 Hz Moreover, the complexes are not as rhythmic, and the spike

component is replaced by longer-duration sharp waves (27) Compared to

3-Hz spike-and-wave pattern, persistent or fluctuating asymmetry of

am-plitude between hemispheres occurs more commonly with the slow

spike-and-wave pattern This pattern is also more likely to occur during waking as

a single discharge of one or a few complexes However, drowsiness or

non-REM sleep may activate trains of repeating slow spike-and-wave complexes,

sometimes similar to electrical status epilepticus during sleep (ESES) HV,

but not photic stimulation, may enhance slow spike-and-waves, but not as

reliably as it does the 3-Hz spike-and-wave pattern The slow spike-and-wave

figure 11.7: slow spike-and-wave, also called sharp-and-slow wave

(in-dicated by arrow), in the patient in Figs 11.2 and 11.9 (interval between

gridlines is 200 milliseconds.)