Use and Abuse of EEG in the Diagnosis of Idiopathic Generalized Epilepsies

Epilepsia, 46(Suppl. 9):96–107, 2005Blackwell Publishing, Inc.C© International League Against Epilepsy

Use and Abuse of EEG in the Diagnosis of IdiopathicGeneralized Epilepsies

∗Michael Koutroumanidis and †Shelagh Smith

∗Department of Clinical Neurophysiology and Epilepsies, St Thomas’ Hospital, and †Department of Clinical Neurophysiology, TheNational Hospital for Neurology and Neurosurgery, London, United Kingdom

Summary: This article concentrates on the role of electroen-cephalograms (EEGs) in the diagnosis and management of pa-tients with idiopathic generalized epilepsies (IGEs). We reviewthe morphologic and behavioral characteristics of the interictaland ictal EEG markers of IGE that should guide recording strate-gies to augment its diagnostic yield, and we attempt to delineatethose particular features that may be relevant to different IGE

syndromes. We also explore the electrographic boundaries be-tween IGEs and cryptogenic/symptomatic generalized and focalepilepsies, and focal/secondary generalized epilepsies, with par-ticular relevance to the phenomena of focal abnormalities andsecondary bilateral synchrony, commenting on possible diag-nostic pitfalls and areas of uncertainty. Key Words: EEG—Differential diagnosis—Idiopathic generalized epilepsies.

It is true that the diagnosis of epilepsy is made primar-ily on clinical grounds, but clinical criteria alone may notbe sufficient for characterization of its type, or infallible.There is evidence that early treatment can reduce the riskof seizure recurrence (1), and its efficacy depends largelyon the appropriate drug choice in relation to the particularclinical syndrome. The EEG can contribute to this diag-nostic refinement at different levels, and by implicationto the overall management of patients with seizures. Late-onset epilepsy is not always partial, and a recent study of300 adult patients with a first unprovoked seizure showedthat the electroencephalogram (EEG) increased the accu-racy of diagnosis (generalized vs. partial epilepsies) from47% (based solely on clinical grounds) to 77% (2), con-firming its value in adults, which is well known to be thecase in children (3). On the other hand, the interictal EEGon its own cannot diagnose or exclude epilepsy and can-not indicate prognosis independently or the likelihood forseizure relapse after discontinuation of antiepileptic drugs(AEDs). This review discusses the particular uses and lim-itations of the EEG in idiopathic generalized epilepsies(IGEs), starting with a note on the relevant concepts, ter-minology, and conventions.

Address correspondence and reprint requests to MichaelKoutroumanidis at Department of Clinical Neurophysiology andEpilepsies Lambeth Wing, 3rd floor, St Thomas’ Hospital, London SE17EH, U.K. E-mail: [email protected]

This supplement has been supported through an unrestricted grantfrom UCB S.A., manufacturers of levetiracetam (Keppra�).

THE CONCEPT OF IDIOPATHIC GENERALIZEDEPILEPSY AND THE CONVENTION OF THE

TERMS GENERALIZED AND FOCAL INEPILEPSIES AND SEIZURES

The idea of generalized epilepsy and its evolution towhat we now perceive as IGE was founded on the originalobservation of 3 Hz generalized spike-and-wave (GSW)discharges by Gibbs and coworkers in 1935 (4,5) in 12children with absences. To explain such a unique electro-clinical association, the so-called centrencephalic modelof generalized epilepsy postulated the existence of a sub-cortical (within the thalamic midline structures, the cen-ter of the encephalon) pacemaker that would trigger andsynchronize the GSW discharges (6). Subsequent clini-cal (7,8) and experimental (9) work showed that GSWdischarges could originate from distinct cortical foci,and so the current model of generalized corticoreticularepilepsy was introduced in 1968 (7) to replace its centren-cephalic predecessor. It is now understood that the cortexis abnormally and unevenly hyperexcitable and respondsby spike-wave activity to essentially physiologic affer-ents from the thalamus and reticular-activating system,while the associated subcortical component becomes sec-ondarily involved in the thalamocortical oscillations thatmaintain the discharge (10). Having identified the cor-tex as primarily abnormal, the electrographic signature ofIGE becomes largely a convention, as together with theperfectly symmetrical, bilateral synchronous and regular3 Hz GSW, it has to allow for any evidence of regional

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EEG IN THE DIAGNOSIS OF IGE 97

(presumed unstable as opposed to the stable symptomatic)cortical hyperexcitability, such as the now well-recognized focal spikes and regional accentuation ofGSW (11,12). The clinical picture of IGE is also lenientand includes a range of—perfectly conceivable withinthe corticoreticular frame and usually short-lived—focalsymptoms and signs, such as unilateral jerks and rota-tory seizures (13–15,16) in juvenile myoclonic epilepsy(JME), versive absences (17), etc. Such a complex andversatile concept of IGE is hard to reconcile with the in-flexible and simplified dichotomy between generalizedand focal or partial for seizures, and generalized andlocalization-related for syndromes of the official Interna-tional League Against Epilepsy (ILAE) seizure and syn-drome classification system (18,19). More importantly,this taxonomy provides no platform for differentiating be-tween what is now understood as IGE with pronouncedregional electroclinical features, and focal epilepsies witha stable (symptomatic) cortical focus and rapid general-ization: seizures with clinical changes that do not indicateinitial involvement of both hemispheres and EEG patternsthat are not initially bilateral must be focal (18) and there-fore cannot exist within IGE (19). Such differentiation,however, is clearly important for the management of peo-ple with epileptic seizures, AED trials, and clinical, epi-demiologic, and genetic research, and should not be ne-gotiable.

What can the role of EEG be in this respect? Fast gen-eralization secondary to a symptomatic focus can mimicIGE (8,20,21); focal and generalized epilepsies may coex-ist (22,23), and focal ictal semeiology in IGEs (13,15,17)should reflect nothing less than regional ictal dischargesof varying duration. EEG interpretation is still empiricaland may be completely meaningless and even misleading

FIG. 1. Left side: Generalized photoparoxysmal response at 50 Hz, transformed into a clearly focal 3.5 Hz rhythmic sharp slow activityover the left posterior quadrant. The patient, a 20-year-old woman with early morning myoclonic seizures and infrequent generalizedtonic–clonic seizures since her early teens reported no symptoms. Right side: Typical for idiopathic generalized epilepsy focal abnormalityin the same patient. Note the superior frontal topography that switched sides in other recordings, the normal regional background, and thelow aftercoming slow (see text, Differentiation from focal epilepsies with fast secondary generalization and the phenomenon of secondarybilateral synchrony: diagnostic uncertainties and pitfalls, and Table 1).

without knowledge of the clinical problem. There are nogolden or infallible EEG rules or criteria for IGE, and itis the whole electroclinical picture of the individual pa-tient that matters and not isolated EEG features. Whatwe are prepared to accept as IGEs depends on our ex-perience and ability to recognize distinct electroclinicalpatterns and presentations and associate them with otherinformation in a meaningful way. In this sense, the termgeneralized is clearly problematic and confusing, and elec-troencephalographers should perhaps shift their attentionfrom elaborating on the mere morphology of a bilateraland diffuse discharge to deducing its aetiology by identi-fying markers that would predict a stable (symptomatic)or unstable (idiopathic) regional hyperexcitability. Figs. 1and 2 show deliberately exaggerated examples of focalEEG responses to photic stimulation in patients whosehabitual clinical seizures, interictal and ictal EEG, andnormal intellect and neuroimaging would perfectly fulfilthe diagnostic criteria of JME, and whose treatment withcarbamazepine would be medical error. Albeit rare, suchcases render any rigid or indeed arbitrary (such as the rateof propagation) (24) electrographic criteria for primaryand secondary generalization superfluous.

EEG CHARACTERISTICS OF IDIOPATHICGENERALIZED EPILEPSIES

The electrographic hallmark of IGEs is a GSW dis-charge (in the sense that it occupies all areas of the cere-brum) that shows an abrupt bilateral and synchronous on-set, repeats itself (when it does so) at three cycles persecond or faster, and is of maximal amplitude over theanterior areas. GSW discharges occur interictally and inassociation with the three main seizure types of IGEs,

Epilepsia, Vol. 46, Suppl. 9, 2005

98 M. KOUTROUMANIDIS AND S. SMITH

FIG. 2. Upper row: Spontaneous during light sleep (left side) and photically induced at 18 Hz (right side) subclinical generalized spike-and-wave discharges in a 22-year-old woman with myoclonic seizures and infrequent generalized tonic–clonic seizures since the age of11 years. Lower row: Monocular photic stimulation at 18 Hz in the same patient provoked a 26 s, perfectly focal subclinical discharge onthe right.

namely typical absences (TA), myoclonic seizures (MS),and generalized tonic–clonic seizures (GTCS). Sponta-neous GTCS, recorded usually during prolonged videoEEG telemetry and only by chance during routine awakeor sleep recordings, can occur either on their own or, per-haps more frequently, follow a volley of MS or a clusterof TA/absence status epilepticus (SE) (25). Backgroundactivity is normal, and interictal focal, nonlocalizing ab-normalities may occur, usually fast spikes over the frontalareas (see section, Differentiation from focal epilepsieswith fast secondary generalization and the phenomenonof secondary bilateral synchrony: diagnostic uncertaintiesand pitfalls, and Table 1).

TYPICAL ABSENCES AND MYOCLONICSEIZURES IN IDIOPATHIC GENERALIZEDEPILEPSIES: MORPHOLOGIC AND OTHER

CHARACTERISTICS

Typical absencesTAs are characterized clinically by impaired conscious-

ness (absence) that occurs without warning and also ceasessuddenly and without postictal symptoms, and electro-

graphically by 3 Hz or faster GSW or generalized poly-spike-and-wave (GPSW) (18) that terminates withoutsubsequent electrical flattening. The term typical distin-guishes these seizures from the slower (2.5 Hz or less)atypical absences in symptomatic or cryptogenic general-ized epilepsies (see section, Differentiation between typ-ical and atypical absences), whereas the term classicalhas been used to characterize the regular archetypical ab-sences of childhood absence epilepsy (CAE) and juvenileabsence epilepsy (JAE), but provides no additional infor-mation. The clinical manifestations of TAs vary signifi-cantly among patients (26–28), as do the associated ictaldischarges, and some electroclinical profiles may be syn-drome related (28). TA may occur alone or coexist withMS and GTCS, appear any time from early childhood toadulthood, occur randomly, in clusters or absence statusepilepticus (SE) (29), and remit with age or persist duringadulthood (30–34). The accompanying GSW dischargemay be very brief or long, continuous or fragmented, withregular or varying intradischarge frequency, may consistof spike or multiple spike components or both, and evenshow nonconsistent side emphasis. It is usually faster andunstable in the opening phase (first second), becomes more



TABLE 1. Differential diagnostic clinical and EEG features between IGE and focal symptomatic epilepsies

Symptomatic focal IGE

HistoryFamily history Rarely positive (familial FLE, TLE) Positive in up to 40%Febrile convulsions Prolonged and complicated SimpleOnset Often during the 2nd half of first decade Usually syndrome specificNatural history Often biphasic (mesial TLE) ContinuousCircadian variation Usually nonspecific Usually specific

Clinical featuresTriggers Unusual Frequent/multipleAura/initial focal signs Frequent RareAutomatisms Involve trunk, arms/hands, and legs. Reactive

automatisms are frequentUp to about 2/3 of TA, rarely involving trunk or legs.

Reactive automatisms occur only in absence SEClonic movements Unilateral and focal. The typical fragment of

motor seizure in FLE but rare in TLE and latein ictal sequence.

When asymmetrical/regional tend to switch sides andmay involve different areas in the same patient(eyelids, proximal or distal upper limbs, etc.)

Postictal symptoms/signs Frequent Never in TA and MSInterictal EEGFocal abnormalities As a rule Up to 30-40%

Morphology Usually single high-voltage spike-wave,sharp-wave (prominent aftercoming slowwave), mono- or polymorphic delta. Verticalasymmetry

Usually >1 foci of low voltage fast spikes or sharpwaves with small aftercoming slow if any. No deltaactivity. Vertical symmetry

Regional background Disturbed NormalPattern of occurrence Consistent, frequent Random, infrequentEffect of sleep Activation NoneTopography Localizing, usually anterior to mid-temporal in

TLE. Stable over sequential recordingsNonlocalizing, usually superior frontal, frontopolar, or

posterior. Shifting, unstable over sequential EEGsElectrical field Relatively large Relatively smallTemporal relation to GSW Possible (criterion for SBS) None

GSW Unusual (? frequency) As a rule“Lead in” pattern from a focal discharge may

exist (82,83)No “lead in” pattern

EEG, electroencephalogram; IGE, idiopathic generalized epilepsy; FLE, frontal lobe epilepsy; TLE, temporal lobe epilepsy; TA, typical absences;SE, status epilepticus; MS, myoclonic seizures; SBS, secondary bilateral synchrony; GSW, generalized spike-and-wave.

regular and stable in the initial phase (next 3 s), and slowsdown towards the terminal phase (last 3 s) (28).

Myoclonic seizuresMS (jerks) are sudden, brief, bilateral symmetrical or

asymmetrical clonic movements of distal/regional or ax-ial muscles that usually occur in clear consciousness andwith varying intensity while awake or sleep, singularly ororganized in rhythmic but more frequently arrhythmic vol-leys, and spontaneously, in association with movements orintention of movements, or in response to simple or com-plex stimuli. From the EEG viewpoint, MS are charac-terized by brief (1–4 s) and fast generalized spike/doublespike/polyspike and wave discharges with anterior max-imum and varying intradischarge frequency. Dischargesmay be symmetrical or show variable side emphasis. MSfrequently occur in some association with TA or GTCS(as in JAE and in most patients with JME) or may be theonly seizure type, such as in benign myoclonic epilepsyin infancy (BMEI) and in some patients with JME. BMEIand JME are the archetypical myoclonic IGE syndromes,whereas the position of eyelid myoclonia with absences(EMA) and perioral myoclonia with absences (PMA) isintermediate between MS and TA as clinically prominent,

repetitive regional myoclonias are associated with impair-ment of cognition and longer GPSW.

Physiologic behavior of generalized spike-and-wavein different states of vigilance, methods of activationand recommended recording strategiesand techniques

Subclinical GSW/GPSW discharges and generalizedseizures may occur spontaneously but may also be pro-voked by hyperventilation and specific triggers (35) (e.g.,photic or pattern (36) stimulation, video games (37), think-ing (38,39), reading and language-induced (40–42) epilep-sies). With regard to reflex activation, specific stimuli ac-tivate the corresponding receptive brain areas or networkswhere the ictal discharge is generated (43,44), and despitethe fact that most of the reflex seizures and epilepsiesare associated with and classified within the IGEs, EEGphenomena such as asymmetrical or skewed (39,45,46)GSW, or generalized photoparoxysmal responses show-ing a clear focal (occipital) onset (47), or continuation(Fig. 1), and even perfectly focal discharges (Fig. 2) areacceptable within the frame of the corticoreticular model.

The spontaneous occurrence of GSW discharges andgeneralized seizures is influenced by the circadian rhythm.Early observations by Gowers (1885) on patients with



seizures occurring mainly or exclusively in the early morn-ing (48) were followed by others, including Janz, who isresponsible for shaping the concept of awakening epilepsy(49,50). This early morning activation, particularly whenawakening is not spontaneous but provoked, applies for allseizures (GTCS, TA, and MS), and is particularly charac-teristic for some syndromes (IGE with GTCS on awaken-ing, JME, and EMA) and less so for others, including CAEand JAE. Forced awakening from daytime naps is also ef-fective, showing that the transitional state from sleep tofull wakefulness is the primary activating factor ratherthan the actual time of awakening. Janz also described asecond peak of seizure occurrence in the evening hours ofrelaxation, but in contrast to the activation on awakening,this state is probably impossible to reproduce in the EEGlab. IGEs are also sleep-sensitive epilepsies: GSW are ac-tivated during drowsiness and light sleep and practicallydisappear during rapid eye movement sleep, regardless ofthe specific subsyndrome. The occurrence of GSW is par-ticularly associated with phasic arousal events without be-havioral awakening (51), and at microstructure sleep levelwith the unstable or dynamic phase of the cyclic alternat-ing pattern that is periodically repeated throughout slowsleep, is associated with EEG desynchronization, and re-flects microarousal responses (52–54). Sleep deprivationseems to activate GSW independently (55,56).

In the evaluation of the patient with newly presentedgeneralized seizures of suspected idiopathic aetiology, theprimary role of the EEG is not to diagnose or excludeepilepsy (57,58) but to support or suggest the diagnosisof IGE by demonstrating GSW in the absence of focalchanges that would imply a symptomatic focus (see sec-tion, Differentiation from focal epilepsies with fast sec-ondary generalization and the phenomenon of secondarybilateral synchrony: diagnostic uncertainties and pitfalls).At a second level, it is desirable to record TA or MS tofacilitate syndromic diagnosis (see section, EEG charac-teristics in different idiopathic generalized epilepsy syn-dromes). Therefore, the first EEG, ideally video and per-formed before starting treatment, should be sufficientlylong and include more than one overbreathing (OB) ses-sion if needed. For sleep EEG, partial SD the night beforealmost guarantees the natural occurrence of sleep, partic-ularly if the recording is arranged for early afternoon, andcontributes to maximal activation in combination with theeffects of drowsiness and light sleep, and of OB and inter-mittent photo stimulation (IPS) performed immediatelyafter provoked awakening. It is good practice to assessfor possible changes of awareness, tone, and abnormalmovements during GSW, for example, by demonstratingon video analysis an otherwise imperceptible hesitation inbreath counting, a mild drop of outstretched arms, or a dis-crete and barely noticeable distal or regional myoclonus.Particular attention is needed when analysing video sleeprecordings containing possible subtle clinical events.

Because of frequently unavoidable long EEG waitinglists and limited time availability, recording strategy mustbe flexible and depend on the clinical setting and availableinformation. In children with typical (pyknoleptic) CAE,for example, simple OB may easily provoke clinical ab-sences and a sleep EEG is rarely needed. In contrast, max-imal activation from the beginning may be required whenthe diagnosis of IGE is possible but not clinically obvious,for instance in children with nonpyknoleptic episodic my-oclonus associated with brief staring, or in adults with his-tory of infrequent GTCS and episodes suggestive of non-convulsive status. A routine EEG during the awake statein such cases is likely to be inconclusive, and thereforea waste of time and resources. Recording of spanioleptic(spanios means infrequent in Greek) absences may requiremore than one sleep EEG and occasionally a brief periodof video telemetry, and the possibility of reflex mecha-nisms must be examined if TAs do not occur despite clearhistorical evidence. Follow-up EEGs may be useful for as-sessing the effectiveness of treatment in children with TAs(see section, EEG and prognosis of idiopathic generalizedepilepsies), reconsideration of the provisional diagnosisin case of treatment failure, and when a new seizure typehas allegedly appeared, signalling either evolution of thenatural history of the disorder or AED-related side ef-fects (such as lamotrigine- or carbamazepine-induced MS(59).

THE PLACE OF EEG IN THE DIAGNOSIS ANDDIFFERENTIAL DIAGNOSIS OF IDIOPATHIC

GENERALIZED EPILEPSY

EEG characteristics in different idiopathicgeneralized epilepsy syndromes

IGE syndromes and conditions predominantlymanifesting with typical absences

These include CAE, JME, and phantom absences withlate-onset GTCS and frequent absence status (PA-GTCS).TAs may occur in about 30% of patients with JME, while asignificant number of patients with IGEs and TAs are im-possible to classify. The actual video-EEG recording ofTA in a child, adolescent, or adult is indispensable for thediagnosis and is usually successful if the recommendedstrategies and techniques are followed (see section, Typi-cal absences and myoclonic seizures in idiopathic gener-alized epilepsies: morphologic and other characteristics).

In CAE, the typical EEG accompaniment of a TA is abilateral synchronous, symmetrical, and regular 3–4 HzSW discharge. The duration ranges from 4–30 s, is usu-ally between 5 and 12 s, and exceptionally longer than 20s (26,28,60–62). Interictally, the EEG is normal or it mayshow brief GSW. Some children exhibit long runs of pos-terior rhythmic delta activity that block on eye opening andincrease by hyperventilation (63). These runs may persist



FIG. 3. Video electroencephalogram (EEG) on a 42-year-old woman with juvenile absence epilepsy (JAE) and photosensitivity with typicalabsences since the age of 11 years and positive family history of seizures. All her EEGs have shown spontaneous (left side) and photicallyinduced (middle) TA, inconsistent bilateral frontopolar fast spikes, and strangely consistent bursts of left temporal rhythmic delta activity(right side). The latter are highly unusual for idiopathic generalized epilepsy and resemble interictal temporal delta activity indicative oftemporal lobe epilepsy (97). She never had any clinical evidence of complex partial seizures though, and brain magnetic resonance imagingwas normal, but she had suffered an episode of encephalitis during childhood that might have induced an apparently nonepileptogenicregional (left temporal) dysfunction that is irrelevant to JAE. The possibility of her absences being symptomatic (secondary to a left temporaldysfunction related to the meningitis) is rather remote and is not supported by the positive family history or electrographically.

after the remission of absences, constituting probably agenetic marker.

In JAE, the morphology of the ictal discharge is notfundamentally different than in CAE (Fig. 3), but TAsare less frequent, and random/infrequent MS and GTCSusually coexist (28,64).

Phantom TAs (brief simple absences that are so mildthat they are inconspicuous to the patient and impercepti-ble to the observer) may associate with late-onset GTCSand frequently with absence status in adults (31), but alsoin children (65). Video EEG (prompted by the GTCS)with breath counting or other cognitive testing during OBis mandatory for the diagnosis, when brief 3–4 Hz regularGSW are shown to interfere with cognitive performance.

Idiopathic generalized epilepsy syndromespredominantly manifesting with myoclonic seizures

In JME, the hallmark of the interictal and ictal dis-charges is the occurrence of polyspike-and-wave activity.Ictally, the number of polyspikes seems to correlate withthe intensity of the myoclonic jerks, and GPSW are usually

brief and irregular, with unstable intradischarge frequency,fragmentations, and multiple spikes that may override theslow components. They may also show fluctuating asym-metry or regional accentuations (14), and interictal focalabnormalities can occur in up to 40% of patients (11)(see section, Differentiation from focal epilepsies withfast secondary generalization and the phenomenon of sec-ondary bilateral synchrony: diagnostic uncertainties andpitfalls, and Fig. 4). Reflex seizure activation occurs fre-quently with variable stimuli; photosensitivity occurs inabout 40% of patients, while less frequent triggers includethinking or other high cognitive processes (38,39), read-ing or other language-related stimuli, and praxis induction(40,41,66). Coexistence of different triggers is possible,and full assessment and confirmation with activated videoEEG studies is important for treatment and management.

In BMEI, MS appear before the age of 3 years, involvethe neck and the proximal upper limbs, and are alwaysassociated with GPSW. Interictal abnormalities are rareand tend to increase during drowsiness and light sleep,and there is no photosensitivity (67).



FIG. 4. Video electroencephalogram (EEG) on a 16-year-old girl with a 2-year history of early morning myoclonic seizures (MS) andtwo generalized tonic–clonic seizures that were preceded by volleys of MS and occurred after sleep deprivation. Left and middle traces:examples of focal and abortive generalized discharges during sleep; Right trace: immediately after provoked awakening, she presentedsequential episodes of diffuse 15–18 Hz fast activity followed by polyspike-and-wave at 3 Hz, consistently induced by eye closure. The fastrhythms were associated with eyelid myoclonia, and the polyspike-wave component with a single jerk of the head to the right. Most of theseepisodes were associated with brief impairment of cognition, as evidenced by hesitations and mistakes in counting. A previous awakeEEG had shown typical MS and photoparoxysmal responses suggestive of juvenile myoclonic epilepsy (JME), but not eyelid myoclonia.It had also prompted treatment with sodium valproate, which had apparently eliminated the early morning MS. This video-EEG recordingafter provoked awakening demonstrated that the true electroclinical phenotype in this girl overlaps between JME and eyelid myocloniawith absences, and that the dose of valproate previously thought to be clinically therapeutic was in fact insufficient.

Idiopathic generalized epilepsy syndromes andconditions predominantly manifesting with prolongedrhythmic myoclonias associated with variableimpairment of consciousness

The hallmarks of EMA are TA associated with clonicmovements of the eyelids (68) and marked photosensitiv-ity. Symptoms usually start in early childhood and may beresistant to treatment. GTCS and random myoclonic jerksof the limbs may occur infrequently most likely after sleepdeprivation, fatigue, and alcohol intake. The ictal EEGmanifestations consist mainly of brief (3–6 s) generalizedbursts of typically polyspike-wave discharges at 3–6 Hz(69,70) that occur mainly after eye closure, and are par-ticularly aggressive on awakening when they can amountto absence SE. Electroclinical overlapping with JME mayexist, reflecting the predominant myoclonic nature of bothsyndromes, and their propensity to manifest with brief,usually mild absences (Fig. 4). Patients practicing self-induction should be differentiated from pure EMA andtreated accordingly (for full discussion on differentiation,including the relevant video-EEG criteria, see references71–75).

Video-EEG studies in PMA have shown that TAs areassociated with regional rhythmic myoclonias of the peri-oral facial muscles, but there are no characteristic featuresin the 3 Hz GSW discharge, and there is no photosensi-tivity. Infrequent GTCS usually coexist, and absence SEmay occur. Seizures may be pharmacoresistant, probablyfor life (76).

Myoclonic absences (MA) are characterized by rhyth-mic (3 Hz) myoclonias of the shoulders, arms, and legs,associated with a tonic contraction of the shoulders thatcauses elevation of the abducted arms, and 3 Hz GSWthat are similar to those in CAE and coincide with themyoclonias. The syndrome of MA is uncommon and theprognosis is favorable when MA (and sometimes simpleTA) is the only seizure type but bad when GTCS and fallscoexist (77).

Idiopathic generalized epilepsy with generalizedtonic–clonic seizures only

This diagnostic entity is meant to include not only pa-tients with GTCS on awakening (GTCSa) but also thosewith GTCS during evening hours of leisure and relaxation



(GTCSe), as well as those with random (GTCSr) or noc-turnal (GTCSn) seizures. Despite the apparent strictnessof the term, there is no consensus on whether or not TAs orMS (or episodes of absence SE) are accepted, and if theyare, to what extent and in what order in the natural history.The current classification system (19) accepts the presenceof TA and MS in GTCSa, allowing for potentially signifi-cant overlap with other IGE syndromes that share the sameseizures and activation on awakening, such as JME. Fromthe clinical viewpoint, a consistent story of MS precedingGTCSa (clonic–tonic–clonic sequence) would be perhapsin keeping with JME, but such seizures can occur in theabsence of independent MS, and in our experience, theusual seizure pattern in the individual patient is a com-bination of clonic–tonic–clonic and tonic–clonic seizuresrather than a pure culture of either. On the other hand,systematic absence of the initial clonic component couldbe also consistent with focal onset and fast generalization.Hence, the role of EEG is clearly important in the diag-nosis and classification of these conditions; sleep record-ings after sleep deprivation with OB on awakening mayreveal previously unnoticed phantom absences and pushthe diagnosis away from GTCSa (or alternatively showthat PA-GTCS are frequent in these patients and lead toamalgamation of the two conditions). On the other hand,the demonstration of GSW during sleep might suggest thediagnosis of IGE in patients with GTCS, and normal in-tellect, neurologic examination and imaging, rather thancryptogenic focal (for example frontal lobe) epilepsy. Theoriginal studies by Christian (1960) hinted that patientswith GTCSa may differ from those with GTCSn in thatGSW activity is present in 40% of the former (and in 70%when TA or MJ are allowed), but in only 3% of the latter(50,78,79), suggesting a different pathophysiology.

Differentiation from focal epilepsies with fastsecondary generalization and the phenomenon ofsecondary bilateral synchrony: diagnosticuncertainties and pitfalls

Misinterpretation of IGEs for focal epilepsies and viceversa is possible and may seriously affect patient treatmentand management, clinical and genetic research, and AEDtrials. From the clinical viewpoint, TA with automatismsmay mimic complex partial seizures, asymmetric MS mayresemble focal motor seizures, and absence SE may sound(and behave) like complex partial SE. Misdiagnosis maybe encouraged by the asymmetric GSW discharges andfocal spikes of IGEs (11,12,14), and by the apparentlysymmetric and regular GSW that may occasionally occurin symptomatic focal epilepsies (21,80). Coexistence offocal and generalized discharges, for example, may re-flect IGE with nonlocalizing focal spikes (11,12), focal ormultifocal symptomatic or cryptogenic epilepsy with sec-ondary bilateral synchrony (81), or coexistence of focalepilepsy and IGE (22,23). The patient with JAE, whose

EEG is depicted in Fig. 3, may exemplify a fourth alter-native. Table 1 lists the main clinical and interictal EEGdifferential diagnostic features, with particular emphasison the focal EEG abnormalities that would characterize id-iopathic and symptomatic syndromes. The list is far fromcomplete, and the reader is reminded that differentiationis a complex diagnostic process that takes into account allclinical and EEG features and may be neither infalliblenor conclusive.

The possibility of secondary bilateral synchrony (SBS),a term coined by Jasper and Tukel in 1952 to distinguishbilateral synchronous discharges that arise from a unilat-eral cortical focus from those thought to arise subcortically(the now-abandoned concept of centroencephalic epilepsyor primary bilateral synchrony (81), is suggested by a con-sistent temporal and spatial relationship between a focalspike and an ensuing bilateral synchronous discharge (82).Blume and Pillay (1985) (83) studied the clinical corre-lates of SBS, using more elaborate criteria that requiredsequential spikes leading to SBS to occur for at least 2s, and the morphology of the focal triggering spikes toclearly differ from that of the bisynchronous paroxysm,and to resemble that of other focal spikes from the sameregion. Half of their patients with SBS were mentally sub-normal, 75% had spike-and-wave (SW) discharges slowerthan 3 Hz, and most had frontal lobe foci. However, suchclear EEG evidence may not be necessarily available, andits absence should not automatically infer the diagnosisof IGE; cortical foci may lie within sulci or secondarygeneralization may be rapid. Occasionally, tumours mayunderlie regular 3 Hz SW (20,84), and typical absencesresponsive to sodium valproate may occur in associationwith periventricular nodular heterotopia (21). The overallassociation between GSW (and sometimes TA) with focalbrain pathology is uncertain; lack of clear EEG evidenceof SBS may be either coincidental, reflecting mere coexis-tence of symptomatic focal epilepsies with IGE, or due tostrategic position of the lesion in the midline (8), perhapsin some association with a genetic predisposition. Cau-tion, of course, is needed to avoid confusion between SBSand the diffuse discharge from a single parasagittal gen-erator whose field extends across the midline. Distinctionof SBS requires the demonstration of two independent butsynchronously firing foci that occupy homologous brainareas, shown in coronal montages that employ midlineelectrodes (85).

Differentiation between typical and atypical absencesAtypical absences occur only in the context of mainly

severe symptomatic or cryptogenic epilepsies of chil-dren with learning difficulties, who also suffer from fre-quent seizures of other types including tonic, atonic, andmyoclonic/myoclonic–atonic seizures such as Lennox–Gastaut syndrome or myoclonic astatic epilepsy. As op-posed to TA, onset and offset may be gradual, impairment



of consciousness is usually mild to moderate and some-times difficult to ascertain, and ictal changes of tone areusually more pronounced. The ictal discharge is slower(<2.5 Hz) and irregular, and may include other paroxys-mal activity, especially during sleep. Background activityis usually abnormal, and consistent focal abnormalities ortrue SBS may exist.

The case of hyperventilation-induced high-voltagerhythmic slowing with or without alteredresponsiveness: electrographic expression ofnonepileptic reduction of awareness or typicalabsences without spikes?

The appearance of diffuse and sometimes of relativelyabrupt onset bursts of rhythmic high voltage 2–5 Hz slowactivity during hyperventilation is frequent in children 8–12 years of age, depends on the effectiveness of over-breathing and the level of blood glucose, and should notbe reported as interictal generalized epileptiform activityunless unequivocal spike wave components are seen (86).The situation may become more complicated on the rareoccasion when such bursts (with or without notches) occurin association with some clinical evidence of reduced re-sponsiveness, including arrest of activity, staring, smiling,yawning, and even oral or manual automatisms. More rig-orous methodology during such bursts has demonstratedimpaired motor responsiveness to auditory stimuli andverbal recall (87), whereas we have found hesitations ofbreath counting. Although different opinions exist (88),the prevailing view is that such electroclinical phenom-ena are nonepileptic in nature (87,89,90) and presumablyrelate to a cumulative physiologic effect that occurs dur-ing hyperventilation, with the “symptomatic” bursts repre-senting one end of a much wider spectrum (90). In clinicalpractice, the diagnosis of absence epilepsy should not beentertained in the absence of a clear spike component ei-ther in such hyperventilation-induced bursts or elsewherein the record, even in children referred because of possi-ble absences. When in doubt or if the clinical evidence iscompelling, repeating the EEG will enhance the chanceto record TAs, or alternatively may disclose the poor con-sistency that characterizes these hyperventilation-inducedbursts of slow in sequential recordings (90). Similar phe-nomena may occur in adults, although less frequently(86).

EEG AND PROGNOSIS OF IDIOPATHICGENERALIZED EPILEPSIES

Several studies have suggested that EEGs may con-tribute to the determination of prognosis, but as with its di-agnostic yield, there are no gold-standard EEG criteria forremittance or persistence of seizures. The following indi-vidual EEG features appear to be of prognostic relevance:children with TAs and occipital intermittent 3 Hz rhythmicdelta activity (OIRDA) are less likely to develop GTCS,

whereas those with photosensitivity likely will (63,91–94). The occurrence of runs of polyspikes preceding atypical 3 Hz GSW has also been associated with persis-tence of TA, pharmacoresistance, and evolution to GTCSseizures (32). Myoclonic elements in TA are also associ-ated with a less favorable outcome (91,92). In a series of139 adults (>16 years of age) with IGE and ictal videoEEG studies from St Thomas’ Epilepsy clinic, a strongmyoclonic component and photosensitivity were inverselyassociated with outcome. Fourteen of 67 patients with pri-marily myoclonic syndromes and conditions (JME, EMA,PMA, JAE with prominent MS, etc.) became seizure-free,as opposed to 28 of 72 with nonmyoclonic (CAE, JAE,PA-GTSC, etc.) (p = 0.027), whereas only seven out of51 photosensitive patients became seizure-free, in contrastto 31 of 72 who were not photosensitive. The predictivevalue of hyperventilation-induced spike-wave activity orTA for outcome is less certain.

Repeat EEG studies may be useful in monitoring theresponse to treatment particularly in children with TA, asthere is a very close correlation between clinical seizurecontrol and electrographic abnormalities (95,96); such arelationship does not exist in other generalized seizures(tonic–clonic or myoclonic) or in partial epilepsies. VideoEEG can therefore monitor the effectiveness of treatmentand prompt dose adjustments if clinically unnoticeable TAare recorded. Withdrawal of AED therapy is not recom-mended while the EEG is still abnormal, and a burnt-outphotoparoxysmal response may revive. Certainly, the pre-dictive value of EEG is not absolute: GSW activity maypersist after clinical recovery, and GTCS may occur in theabsence of interictal EEG abnormalities (93).

CONCLUSIVE REMARKS

In summary, the EEG can

• Support the diagnosis of IGE and assist its differentialdiagnosis from:◦ symptomatic focal epilepsies with fast generaliza-

tion.◦ symptomatic generalized epilepsy.

• Delineate the full clinical picture by video recordingof all seizure types and variations, with implicationsfor◦ Syndromic diagnosis.◦ Optimal selection of AED (i.e., clonazepam or lev-

etiracetam when MS are prominent; lamotrigine ifTA predominate)

• Detect specific triggers or self-induction.• Diagnose nonepileptic conditions that mimic IGEs

(i.e., staring attacks or hyperventilation-inducedhigh-voltage rhythmic slowing mimicking TA, orjerks not associated with GSW discharges).

• Assist in prognostication.



• Monitor AED treatment and predict possible relapseafter AED discontinuation (mainly in children withTA).

• Detect/confirm new seizure types that may signal ei-ther evolution of natural history or adverse effects ofAED.

• Detect signs of AED intoxication.• Record previously unidentified seizures/interictal

patterns/triggers when reconsidering initial diagno-sis and reclassification after treatment failure.

Interictal EEG alone cannot be used for

• Establishing or excluding the diagnosis of epilepsy(including IGEs).

• Providing oversimplified clues for reliable syn-dromic diagnosis (GSW do not always indicate IGE,and focal changes do not necessarily suggest a symp-tomatic focus).

• Prognostication and prediction of possible relapse af-ter the discontinuation of AED treatment.

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Use and Abuse of EEG in the Diagnosis of Idiopathic Generalized Epilepsies