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Keywords:

  • EEG;
  • Differential diagnosis;
  • Idiopathic generalized epilepsies

Abstract

  1. Top of page
  2. Abstract
  3. THE CONCEPT OF IDIOPATHIC GENERALIZED EPILEPSY AND THE CONVENTION OF THE TERMS GENERALIZED AND FOCAL IN EPILEPSIES AND SEIZURES
  4. EEG CHARACTERISTICS OF IDIOPATHIC GENERALIZED EPILEPSIES
  5. TYPICAL ABSENCES AND MYOCLONIC SEIZURES IN IDIOPATHIC GENERALIZED EPILEPSIES: MORPHOLOGIC AND OTHER CHARACTERISTICS
  6. THE PLACE OF EEG IN THE DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS OF IDIOPATHIC GENERALIZED EPILEPSY
  7. EEG AND PROGNOSIS OF IDIOPATHIC GENERALIZED EPILEPSIES
  8. CONCLUSIVE REMARKS
  9. REFERENCES

Summary:  This article concentrates on the role of electroencephalograms (EEGs) in the diagnosis and management of patients with idiopathic generalized epilepsies (IGEs). We review the morphologic and behavioral characteristics of the interictal and ictal EEG markers of IGE that should guide recording strategies to augment its diagnostic yield, and we attempt to delineate those particular features that may be relevant to different IGE syndromes. We also explore the electrographic boundaries between IGEs and cryptogenic/symptomatic generalized and focal epilepsies, and focal/secondary generalized epilepsies, with particular relevance to the phenomena of focal abnormalities and secondary bilateral synchrony, commenting on possible diagnostic pitfalls and areas of uncertainty.

It is true that the diagnosis of epilepsy is made primarily on clinical grounds, but clinical criteria alone may not be sufficient for characterization of its type, or infallible. There is evidence that early treatment can reduce the risk of seizure recurrence (1), and its efficacy depends largely on the appropriate drug choice in relation to the particular clinical syndrome. The EEG can contribute to this diagnostic refinement at different levels, and by implication to the overall management of patients with seizures. Late-onset epilepsy is not always partial, and a recent study of 300 adult patients with a first unprovoked seizure showed that the electroencephalogram (EEG) increased the accuracy of diagnosis (generalized vs. partial epilepsies) from 47% (based solely on clinical grounds) to 77% (2), confirming its value in adults, which is well known to be the case in children (3). On the other hand, the interictal EEG on its own cannot diagnose or exclude epilepsy and cannot indicate prognosis independently or the likelihood for seizure relapse after discontinuation of antiepileptic drugs (AEDs). This review discusses the particular uses and limitations of the EEG in idiopathic generalized epilepsies (IGEs), starting with a note on the relevant concepts, terminology, and conventions.

THE CONCEPT OF IDIOPATHIC GENERALIZED EPILEPSY AND THE CONVENTION OF THE TERMS GENERALIZED AND FOCAL IN EPILEPSIES AND SEIZURES

  1. Top of page
  2. Abstract
  3. THE CONCEPT OF IDIOPATHIC GENERALIZED EPILEPSY AND THE CONVENTION OF THE TERMS GENERALIZED AND FOCAL IN EPILEPSIES AND SEIZURES
  4. EEG CHARACTERISTICS OF IDIOPATHIC GENERALIZED EPILEPSIES
  5. TYPICAL ABSENCES AND MYOCLONIC SEIZURES IN IDIOPATHIC GENERALIZED EPILEPSIES: MORPHOLOGIC AND OTHER CHARACTERISTICS
  6. THE PLACE OF EEG IN THE DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS OF IDIOPATHIC GENERALIZED EPILEPSY
  7. EEG AND PROGNOSIS OF IDIOPATHIC GENERALIZED EPILEPSIES
  8. CONCLUSIVE REMARKS
  9. REFERENCES

The idea of generalized epilepsy and its evolution to what we now perceive as IGE was founded on the original observation of 3 Hz generalized spike-and-wave (GSW) discharges by Gibbs and coworkers in 1935 (4,5) in 12 children with absences. To explain such a unique electroclinical association, the so-called centrencephalic model of generalized epilepsy postulated the existence of a subcortical (within the thalamic midline structures, the center of the encephalon) pacemaker that would trigger and synchronize the GSW discharges (6). Subsequent clinical (7,8) and experimental (9) work showed that GSW discharges could originate from distinct cortical foci, and so the current model of generalized corticoreticular epilepsy was introduced in 1968 (7) to replace its centrencephalic predecessor. It is now understood that the cortex is abnormally and unevenly hyperexcitable and responds by spike-wave activity to essentially physiologic afferents from the thalamus and reticular-activating system, while the associated subcortical component becomes secondarily involved in the thalamocortical oscillations that maintain the discharge (10). Having identified the cortex as primarily abnormal, the electrographic signature of IGE becomes largely a convention, as together with the perfectly symmetrical, bilateral synchronous and regular 3 Hz GSW, it has to allow for any evidence of regional (presumed unstable as opposed to the stable symptomatic) cortical hyperexcitability, such as the now well-recognized focal spikes and regional accentuation of GSW (11,12). The clinical picture of IGE is also lenient and includes a range of—perfectly conceivable within the corticoreticular frame and usually short-lived—focal symptoms and signs, such as unilateral jerks and rotatory seizures (13–15,16) in juvenile myoclonic epilepsy (JME), versive absences (17), etc. Such a complex and versatile concept of IGE is hard to reconcile with the inflexible and simplified dichotomy between generalized and focal or partial for seizures, and generalized and localization-related for syndromes of the official International League Against Epilepsy (ILAE) seizure and syndrome classification system (18,19). More importantly, this taxonomy provides no platform for differentiating between what is now understood as IGE with pronounced regional electroclinical features, and focal epilepsies with a stable (symptomatic) cortical focus and rapid generalization: seizures with clinical changes that do not indicate initial involvement of both hemispheres and EEG patterns that are not initially bilateral must be focal (18) and therefore cannot exist within IGE (19). Such differentiation, however, is clearly important for the management of people with epileptic seizures, AED trials, and clinical, epidemiologic, and genetic research, and should not be negotiable.

What can the role of EEG be in this respect? Fast generalization secondary to a symptomatic focus can mimic IGE (8,20,21); focal and generalized epilepsies may coexist (22,23), and focal ictal semeiology in IGEs (13,15,17) should reflect nothing less than regional ictal discharges of varying duration. EEG interpretation is still empirical and may be completely meaningless and even misleading without knowledge of the clinical problem. There are no golden or infallible EEG rules or criteria for IGE, and it is the whole electroclinical picture of the individual patient that matters and not isolated EEG features. What we are prepared to accept as IGEs depends on our experience and ability to recognize distinct electroclinical patterns and presentations and associate them with other information in a meaningful way. In this sense, the term generalized is clearly problematic and confusing, and electroencephalographers should perhaps shift their attention from elaborating on the mere morphology of a bilateral and diffuse discharge to deducing its aetiology by identifying markers that would predict a stable (symptomatic) or unstable (idiopathic) regional hyperexcitability. Figs. 1 and 2 show deliberately exaggerated examples of focal EEG responses to photic stimulation in patients whose habitual clinical seizures, interictal and ictal EEG, and normal intellect and neuroimaging would perfectly fulfil the diagnostic criteria of JME, and whose treatment with carbamazepine would be medical error. Albeit rare, such cases render any rigid or indeed arbitrary (such as the rate of propagation) (24) electrographic criteria for primary and secondary generalization superfluous.

image

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

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image

Figure 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 of 11 years. Lower row: Monocular photic stimulation at 18 Hz in the same patient provoked a 26 s, perfectly focal subclinical discharge on the right.

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EEG CHARACTERISTICS OF IDIOPATHIC GENERALIZED EPILEPSIES

  1. Top of page
  2. Abstract
  3. THE CONCEPT OF IDIOPATHIC GENERALIZED EPILEPSY AND THE CONVENTION OF THE TERMS GENERALIZED AND FOCAL IN EPILEPSIES AND SEIZURES
  4. EEG CHARACTERISTICS OF IDIOPATHIC GENERALIZED EPILEPSIES
  5. TYPICAL ABSENCES AND MYOCLONIC SEIZURES IN IDIOPATHIC GENERALIZED EPILEPSIES: MORPHOLOGIC AND OTHER CHARACTERISTICS
  6. THE PLACE OF EEG IN THE DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS OF IDIOPATHIC GENERALIZED EPILEPSY
  7. EEG AND PROGNOSIS OF IDIOPATHIC GENERALIZED EPILEPSIES
  8. CONCLUSIVE REMARKS
  9. REFERENCES

The electrographic hallmark of IGEs is a GSW discharge (in the sense that it occupies all areas of the cerebrum) that shows an abrupt bilateral and synchronous onset, repeats itself (when it does so) at three cycles per second or faster, and is of maximal amplitude over the anterior areas. GSW discharges occur interictally and in association with the three main seizure types of IGEs, namely typical absences (TA), myoclonic seizures (MS), and generalized tonic–clonic seizures (GTCS). Spontaneous GTCS, recorded usually during prolonged video EEG telemetry and only by chance during routine awake or sleep recordings, can occur either on their own or, perhaps more frequently, follow a volley of MS or a cluster of TA/absence status epilepticus (SE) (25). Background activity is normal, and interictal focal, nonlocalizing abnormalities may occur, usually fast spikes over the frontal areas (see section, Differentiation from focal epilepsies with fast secondary generalization and the phenomenon of secondary bilateral synchrony: diagnostic uncertainties and pitfalls, and Table 1).

Table 1. Differential diagnostic clinical and EEG features between IGE and focal symptomatic epilepsies
 Symptomatic focalIGE
  1. 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.

History
 Family historyRarely positive (familial FLE, TLE)Positive in up to 40%
 Febrile convulsionsProlonged and complicatedSimple
 OnsetOften during the 2nd half of first decadeUsually syndrome specific
 Natural historyOften biphasic (mesial TLE)Continuous
 Circadian variationUsually nonspecificUsually specific
Clinical features
 TriggersUnusualFrequent/multiple
 Aura/initial focal signsFrequentRare
 AutomatismsInvolve 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 SE
 Clonic movementsUnilateral and focal. The typical fragment of motor seizure in FLE but rare in TLE and late in ictal sequence.When asymmetrical/regional tend to switch sides and may involve different areas in the same patient (eyelids, proximal or distal upper limbs, etc.)
 Postictal symptoms/signsFrequentNever in TA and MS
Interictal EEG
Focal abnormalitiesAs a ruleUp to 30-40%
 MorphologyUsually single high-voltage spike-wave, sharp-wave (prominent aftercoming slow wave), mono- or polymorphic delta. Vertical asymmetryUsually >1 foci of low voltage fast spikes or sharp waves with small aftercoming slow if any. No delta activity. Vertical symmetry
 Regional backgroundDisturbedNormal
 Pattern of occurrenceConsistent, frequentRandom, infrequent
 Effect of sleepActivationNone
 TopographyLocalizing, usually anterior to mid-temporal in TLE. Stable over sequential recordingsNonlocalizing, usually superior frontal, frontopolar, or posterior. Shifting, unstable over sequential EEGs
 Electrical fieldRelatively largeRelatively small
 Temporal relation to GSWPossible (criterion for SBS)None
GSWUnusual (? frequency)As a rule
“Lead in” pattern from a focal discharge may exist (82,83)No “lead in” pattern

TYPICAL ABSENCES AND MYOCLONIC SEIZURES IN IDIOPATHIC GENERALIZED EPILEPSIES: MORPHOLOGIC AND OTHER CHARACTERISTICS

  1. Top of page
  2. Abstract
  3. THE CONCEPT OF IDIOPATHIC GENERALIZED EPILEPSY AND THE CONVENTION OF THE TERMS GENERALIZED AND FOCAL IN EPILEPSIES AND SEIZURES
  4. EEG CHARACTERISTICS OF IDIOPATHIC GENERALIZED EPILEPSIES
  5. TYPICAL ABSENCES AND MYOCLONIC SEIZURES IN IDIOPATHIC GENERALIZED EPILEPSIES: MORPHOLOGIC AND OTHER CHARACTERISTICS
  6. THE PLACE OF EEG IN THE DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS OF IDIOPATHIC GENERALIZED EPILEPSY
  7. EEG AND PROGNOSIS OF IDIOPATHIC GENERALIZED EPILEPSIES
  8. CONCLUSIVE REMARKS
  9. REFERENCES

Typical absences

TAs are characterized clinically by impaired consciousness (absence) that occurs without warning and also ceases suddenly and without postictal symptoms, and electrographically by 3 Hz or faster GSW or generalized poly-spike-and-wave (GPSW) (18) that terminates without subsequent electrical flattening. The term typical distinguishes these seizures from the slower (2.5 Hz or less) atypical absences in symptomatic or cryptogenic generalized epilepsies (see section, Differentiation between typical and atypical absences), whereas the term classical has been used to characterize the regular archetypical absences of childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE), but provides no additional information. The clinical manifestations of TAs vary significantly among patients (26–28), as do the associated ictal discharges, and some electroclinical profiles may be syndrome related (28). TA may occur alone or coexist with MS and GTCS, appear any time from early childhood to adulthood, occur randomly, in clusters or absence status epilepticus (SE) (29), and remit with age or persist during adulthood (30–34). The accompanying GSW discharge may be very brief or long, continuous or fragmented, with regular or varying intradischarge frequency, may consist of spike or multiple spike components or both, and even show nonconsistent side emphasis. It is usually faster and unstable in the opening phase (first second), becomes more regular and stable in the initial phase (next 3 s), and slows down towards the terminal phase (last 3 s) (28).

Myoclonic seizures

MS (jerks) are sudden, brief, bilateral symmetrical or asymmetrical clonic movements of distal/regional or axial muscles that usually occur in clear consciousness and with varying intensity while awake or sleep, singularly or organized in rhythmic but more frequently arrhythmic volleys, and spontaneously, in association with movements or intention of movements, or in response to simple or complex stimuli. From the EEG viewpoint, MS are characterized by brief (1–4 s) and fast generalized spike/double spike/polyspike and wave discharges with anterior maximum and varying intradischarge frequency. Discharges may be symmetrical or show variable side emphasis. MS frequently occur in some association with TA or GTCS (as in JAE and in most patients with JME) or may be the only seizure type, such as in benign myoclonic epilepsy in infancy (BMEI) and in some patients with JME. BMEI and JME are the archetypical myoclonic IGE syndromes, whereas the position of eyelid myoclonia with absences (EMA) and perioral myoclonia with absences (PMA) is intermediate between MS and TA as clinically prominent, repetitive regional myoclonias are associated with impairment of cognition and longer GPSW.

Physiologic behavior of generalized spike-and-wave in different states of vigilance, methods of activation and recommended recording strategies and techniques

Subclinical GSW/GPSW discharges and generalized seizures may occur spontaneously but may also be provoked by hyperventilation and specific triggers (35) (e.g., photic or pattern (36) stimulation, video games (37), thinking (38,39), reading and language-induced (40–42) epilepsies). With regard to reflex activation, specific stimuli activate the corresponding receptive brain areas or networks where the ictal discharge is generated (43,44), and despite the fact that most of the reflex seizures and epilepsies are associated with and classified within the IGEs, EEG phenomena such as asymmetrical or skewed (39,45,46) GSW, or generalized photoparoxysmal responses showing a clear focal (occipital) onset (47), or continuation (Fig. 1), and even perfectly focal discharges (Fig. 2) are acceptable within the frame of the corticoreticular model.

The spontaneous occurrence of GSW discharges and generalized seizures is influenced by the circadian rhythm. Early observations by Gowers (1885) on patients with seizures occurring mainly or exclusively in the early morning (48) were followed by others, including Janz, who is responsible for shaping the concept of awakening epilepsy (49,50). This early morning activation, particularly when awakening is not spontaneous but provoked, applies for all seizures (GTCS, TA, and MS), and is particularly characteristic for some syndromes (IGE with GTCS on awakening, JME, and EMA) and less so for others, including CAE and JAE. Forced awakening from daytime naps is also effective, showing that the transitional state from sleep to full wakefulness is the primary activating factor rather than the actual time of awakening. Janz also described a second peak of seizure occurrence in the evening hours of relaxation, but in contrast to the activation on awakening, this state is probably impossible to reproduce in the EEG lab. IGEs are also sleep-sensitive epilepsies: GSW are activated during drowsiness and light sleep and practically disappear during rapid eye movement sleep, regardless of the specific subsyndrome. The occurrence of GSW is particularly associated with phasic arousal events without behavioral awakening (51), and at microstructure sleep level with the unstable or dynamic phase of the cyclic alternating pattern that is periodically repeated throughout slow sleep, is associated with EEG desynchronization, and reflects microarousal responses (52–54). Sleep deprivation seems to activate GSW independently (55,56).

In the evaluation of the patient with newly presented generalized seizures of suspected idiopathic aetiology, the primary role of the EEG is not to diagnose or exclude epilepsy (57,58) but to support or suggest the diagnosis of IGE by demonstrating GSW in the absence of focal changes that would imply a symptomatic focus (see section, Differentiation from focal epilepsies with fast secondary generalization and the phenomenon of secondary bilateral synchrony: diagnostic uncertainties and pitfalls). At a second level, it is desirable to record TA or MS to facilitate syndromic diagnosis (see section, EEG characteristics in different idiopathic generalized epilepsy syndromes). Therefore, the first EEG, ideally video and performed before starting treatment, should be sufficiently long and include more than one overbreathing (OB) session if needed. For sleep EEG, partial SD the night before almost guarantees the natural occurrence of sleep, particularly if the recording is arranged for early afternoon, and contributes to maximal activation in combination with the effects of drowsiness and light sleep, and of OB and intermittent photo stimulation (IPS) performed immediately after provoked awakening. It is good practice to assess for possible changes of awareness, tone, and abnormal movements during GSW, for example, by demonstrating on video analysis an otherwise imperceptible hesitation in breath counting, a mild drop of outstretched arms, or a discrete and barely noticeable distal or regional myoclonus. Particular attention is needed when analysing video sleep recordings containing possible subtle clinical events.

Because of frequently unavoidable long EEG waiting lists and limited time availability, recording strategy must be flexible and depend on the clinical setting and available information. In children with typical (pyknoleptic) CAE, for example, simple OB may easily provoke clinical absences and a sleep EEG is rarely needed. In contrast, maximal activation from the beginning may be required when the diagnosis of IGE is possible but not clinically obvious, for instance in children with nonpyknoleptic episodic myoclonus associated with brief staring, or in adults with history of infrequent GTCS and episodes suggestive of nonconvulsive status. A routine EEG during the awake state in such cases is likely to be inconclusive, and therefore a waste of time and resources. Recording of spanioleptic (spanios means infrequent in Greek) absences may require more than one sleep EEG and occasionally a brief period of video telemetry, and the possibility of reflex mechanisms must be examined if TAs do not occur despite clear historical evidence. Follow-up EEGs may be useful for assessing the effectiveness of treatment in children with TAs (see section, EEG and prognosis of idiopathic generalized epilepsies), reconsideration of the provisional diagnosis in case of treatment failure, and when a new seizure type has allegedly appeared, signalling either evolution of the natural history of the disorder or AED-related side effects (such as lamotrigine- or carbamazepine-induced MS (59).

THE PLACE OF EEG IN THE DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS OF IDIOPATHIC GENERALIZED EPILEPSY

  1. Top of page
  2. Abstract
  3. THE CONCEPT OF IDIOPATHIC GENERALIZED EPILEPSY AND THE CONVENTION OF THE TERMS GENERALIZED AND FOCAL IN EPILEPSIES AND SEIZURES
  4. EEG CHARACTERISTICS OF IDIOPATHIC GENERALIZED EPILEPSIES
  5. TYPICAL ABSENCES AND MYOCLONIC SEIZURES IN IDIOPATHIC GENERALIZED EPILEPSIES: MORPHOLOGIC AND OTHER CHARACTERISTICS
  6. THE PLACE OF EEG IN THE DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS OF IDIOPATHIC GENERALIZED EPILEPSY
  7. EEG AND PROGNOSIS OF IDIOPATHIC GENERALIZED EPILEPSIES
  8. CONCLUSIVE REMARKS
  9. REFERENCES

EEG characteristics in different idiopathic generalized epilepsy syndromes

IGE syndromes and conditions predominantly manifesting with typical absences

These include CAE, JME, and phantom absences with late-onset GTCS and frequent absence status (PA-GTCS). TAs may occur in about 30% of patients with JME, while a significant number of patients with IGEs and TAs are impossible to classify. The actual video-EEG recording of TA in a child, adolescent, or adult is indispensable for the diagnosis and is usually successful if the recommended strategies and techniques are followed (see section, Typical absences and myoclonic seizures in idiopathic generalized epilepsies: morphologic and other characteristics).

In CAE, the typical EEG accompaniment of a TA is a bilateral synchronous, symmetrical, and regular 3–4 Hz SW discharge. The duration ranges from 4–30 s, is usually between 5 and 12 s, and exceptionally longer than 20 s (26,28,60–62). Interictally, the EEG is normal or it may show brief GSW. Some children exhibit long runs of posterior rhythmic delta activity that block on eye opening and increase by hyperventilation (63). These runs may persist after the remission of absences, constituting probably a genetic marker.

In JAE, the morphology of the ictal discharge is not fundamentally different than in CAE (Fig. 3), but TAs are less frequent, and random/infrequent MS and GTCS usually coexist (28,64).

image

Figure 3. Video electroencephalogram (EEG) on a 42-year-old woman with juvenile absence epilepsy (JAE) and photosensitivity with typical absences since the age of 11 years and positive family history of seizures. All her EEGs have shown spontaneous (left side) and photically induced (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 of temporal lobe epilepsy (97). She never had any clinical evidence of complex partial seizures though, and brain magnetic resonance imaging was normal, but she had suffered an episode of encephalitis during childhood that might have induced an apparently nonepileptogenic regional (left temporal) dysfunction that is irrelevant to JAE. The possibility of her absences being symptomatic (secondary to a left temporal dysfunction related to the meningitis) is rather remote and is not supported by the positive family history or electrographically.

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

Idiopathic generalized epilepsy syndromes predominantly manifesting with myoclonic seizures

In JME, the hallmark of the interictal and ictal discharges is the occurrence of polyspike-and-wave activity. Ictally, the number of polyspikes seems to correlate with the intensity of the myoclonic jerks, and GPSW are usually brief and irregular, with unstable intradischarge frequency, fragmentations, and multiple spikes that may override the slow components. They may also show fluctuating asymmetry or regional accentuations (14), and interictal focal abnormalities can occur in up to 40% of patients (11) (see section, Differentiation from focal epilepsies with fast secondary generalization and the phenomenon of secondary bilateral synchrony: diagnostic uncertainties and pitfalls, and Fig. 4). Reflex seizure activation occurs frequently with variable stimuli; photosensitivity occurs in about 40% of patients, while less frequent triggers include thinking or other high cognitive processes (38,39), reading or other language-related stimuli, and praxis induction (40,41,66). Coexistence of different triggers is possible, and full assessment and confirmation with activated video EEG studies is important for treatment and management.

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Figure 4. Video electroencephalogram (EEG) on a 16-year-old girl with a 2-year history of early morning myoclonic seizures (MS) and two 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 presented sequential episodes of diffuse 15–18 Hz fast activity followed by polyspike-and-wave at 3 Hz, consistently induced by eye closure. The fast rhythms were associated with eyelid myoclonia, and the polyspike-wave component with a single jerk of the head to the right. Most of these episodes were associated with brief impairment of cognition, as evidenced by hesitations and mistakes in counting. A previous awake EEG 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 recording after provoked awakening demonstrated that the true electroclinical phenotype in this girl overlaps between JME and eyelid myoclonia with absences, and that the dose of valproate previously thought to be clinically therapeutic was in fact insufficient.

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

Idiopathic generalized epilepsy syndromes and conditions predominantly manifesting with prolonged rhythmic myoclonias associated with variable impairment of consciousness

The hallmarks of EMA are TA associated with clonic movements of the eyelids (68) and marked photosensitivity. Symptoms usually start in early childhood and may be resistant to treatment. GTCS and random myoclonic jerks of the limbs may occur infrequently most likely after sleep deprivation, fatigue, and alcohol intake. The ictal EEG manifestations consist mainly of brief (3–6 s) generalized bursts of typically polyspike-wave discharges at 3–6 Hz (69,70) that occur mainly after eye closure, and are particularly aggressive on awakening when they can amount to absence SE. Electroclinical overlapping with JME may exist, reflecting the predominant myoclonic nature of both syndromes, and their propensity to manifest with brief, usually mild absences (Fig. 4). Patients practicing self-induction should be differentiated from pure EMA and treated accordingly (for full discussion on differentiation, including the relevant video-EEG criteria, see references 71–75).

Video-EEG studies in PMA have shown that TAs are associated with regional rhythmic myoclonias of the perioral facial muscles, but there are no characteristic features in the 3 Hz GSW discharge, and there is no photosensitivity. Infrequent GTCS usually coexist, and absence SE may occur. Seizures may be pharmacoresistant, probably for life (76).

Myoclonic absences (MA) are characterized by rhythmic (3 Hz) myoclonias of the shoulders, arms, and legs, associated with a tonic contraction of the shoulders that causes elevation of the abducted arms, and 3 Hz GSW that are similar to those in CAE and coincide with the myoclonias. The syndrome of MA is uncommon and the prognosis is favorable when MA (and sometimes simple TA) is the only seizure type but bad when GTCS and falls coexist (77).

Idiopathic generalized epilepsy with generalized tonic–clonic seizures only

This diagnostic entity is meant to include not only patients with GTCS on awakening (GTCSa) but also those with GTCS during evening hours of leisure and relaxation (GTCSe), as well as those with random (GTCSr) or nocturnal (GTCSn) seizures. Despite the apparent strictness of the term, there is no consensus on whether or not TAs or MS (or episodes of absence SE) are accepted, and if they are, to what extent and in what order in the natural history. The current classification system (19) accepts the presence of TA and MS in GTCSa, allowing for potentially significant overlap with other IGE syndromes that share the same seizures and activation on awakening, such as JME. From the clinical viewpoint, a consistent story of MS preceding GTCSa (clonic–tonic–clonic sequence) would be perhaps in keeping with JME, but such seizures can occur in the absence of independent MS, and in our experience, the usual seizure pattern in the individual patient is a combination of clonic–tonic–clonic and tonic–clonic seizures rather than a pure culture of either. On the other hand, systematic absence of the initial clonic component could be also consistent with focal onset and fast generalization. Hence, the role of EEG is clearly important in the diagnosis and classification of these conditions; sleep recordings after sleep deprivation with OB on awakening may reveal previously unnoticed phantom absences and push the diagnosis away from GTCSa (or alternatively show that PA-GTCS are frequent in these patients and lead to amalgamation of the two conditions). On the other hand, the demonstration of GSW during sleep might suggest the diagnosis of IGE in patients with GTCS, and normal intellect, neurologic examination and imaging, rather than cryptogenic focal (for example frontal lobe) epilepsy. The original studies by Christian (1960) hinted that patients with GTCSa may differ from those with GTCSn in that GSW 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 fast secondary generalization and the phenomenon of secondary bilateral synchrony: diagnostic uncertainties and pitfalls

Misinterpretation of IGEs for focal epilepsies and vice versa is possible and may seriously affect patient treatment and management, clinical and genetic research, and AED trials. From the clinical viewpoint, TA with automatisms may mimic complex partial seizures, asymmetric MS may resemble focal motor seizures, and absence SE may sound (and behave) like complex partial SE. Misdiagnosis may be encouraged by the asymmetric GSW discharges and focal spikes of IGEs (11,12,14), and by the apparently symmetric and regular GSW that may occasionally occur in symptomatic focal epilepsies (21,80). Coexistence of focal and generalized discharges, for example, may reflect IGE with nonlocalizing focal spikes (11,12), focal or multifocal symptomatic or cryptogenic epilepsy with secondary bilateral synchrony (81), or coexistence of focal epilepsy and IGE (22,23). The patient with JAE, whose EEG is depicted in Fig. 3, may exemplify a fourth alternative. Table 1 lists the main clinical and interictal EEG differential diagnostic features, with particular emphasis on the focal EEG abnormalities that would characterize idiopathic and symptomatic syndromes. The list is far from complete, and the reader is reminded that differentiation is a complex diagnostic process that takes into account all clinical and EEG features and may be neither infallible nor conclusive.

The possibility of secondary bilateral synchrony (SBS), a term coined by Jasper and Tükel in 1952 to distinguish bilateral synchronous discharges that arise from a unilateral cortical focus from those thought to arise subcortically (the now-abandoned concept of centroencephalic epilepsy or primary bilateral synchrony (81), is suggested by a consistent temporal and spatial relationship between a focal spike and an ensuing bilateral synchronous discharge (82). Blume and Pillay (1985) (83) studied the clinical correlates of SBS, using more elaborate criteria that required sequential spikes leading to SBS to occur for at least 2 s, and the morphology of the focal triggering spikes to clearly differ from that of the bisynchronous paroxysm, and to resemble that of other focal spikes from the same region. Half of their patients with SBS were mentally subnormal, 75% had spike-and-wave (SW) discharges slower than 3 Hz, and most had frontal lobe foci. However, such clear EEG evidence may not be necessarily available, and its absence should not automatically infer the diagnosis of IGE; cortical foci may lie within sulci or secondary generalization may be rapid. Occasionally, tumours may underlie regular 3 Hz SW (20,84), and typical absences responsive to sodium valproate may occur in association with periventricular nodular heterotopia (21). The overall association between GSW (and sometimes TA) with focal brain pathology is uncertain; lack of clear EEG evidence of SBS may be either coincidental, reflecting mere coexistence of symptomatic focal epilepsies with IGE, or due to strategic position of the lesion in the midline (8), perhaps in some association with a genetic predisposition. Caution, of course, is needed to avoid confusion between SBS and the diffuse discharge from a single parasagittal generator whose field extends across the midline. Distinction of SBS requires the demonstration of two independent but synchronously firing foci that occupy homologous brain areas, shown in coronal montages that employ midline electrodes (85).

Differentiation between typical and atypical absences

Atypical absences occur only in the context of mainly severe symptomatic or cryptogenic epilepsies of children with learning difficulties, who also suffer from frequent seizures of other types including tonic, atonic, and myoclonic/myoclonic–atonic seizures such as Lennox–Gastaut syndrome or myoclonic astatic epilepsy. As opposed to TA, onset and offset may be gradual, impairment of consciousness is usually mild to moderate and sometimes difficult to ascertain, and ictal changes of tone are usually more pronounced. The ictal discharge is slower (<2.5 Hz) and irregular, and may include other paroxysmal activity, especially during sleep. Background activity is usually abnormal, and consistent focal abnormalities or true SBS may exist.

The case of hyperventilation-induced high-voltage rhythmic slowing with or without altered responsiveness: electrographic expression of nonepileptic reduction of awareness or typical absences without spikes?

The appearance of diffuse and sometimes of relatively abrupt onset bursts of rhythmic high voltage 2–5 Hz slow activity during hyperventilation is frequent in children 8–12 years of age, depends on the effectiveness of overbreathing and the level of blood glucose, and should not be reported as interictal generalized epileptiform activity unless unequivocal spike wave components are seen (86). The situation may become more complicated on the rare occasion when such bursts (with or without notches) occur in association with some clinical evidence of reduced responsiveness, including arrest of activity, staring, smiling, yawning, and even oral or manual automatisms. More rigorous methodology during such bursts has demonstrated impaired motor responsiveness to auditory stimuli and verbal recall (87), whereas we have found hesitations of breath counting. Although different opinions exist (88), the prevailing view is that such electroclinical phenomena are nonepileptic in nature (87,89,90) and presumably relate to a cumulative physiologic effect that occurs during hyperventilation, with the “symptomatic” bursts representing one end of a much wider spectrum (90). In clinical practice, the diagnosis of absence epilepsy should not be entertained in the absence of a clear spike component either in such hyperventilation-induced bursts or elsewhere in the record, even in children referred because of possible absences. When in doubt or if the clinical evidence is compelling, repeating the EEG will enhance the chance to record TAs, or alternatively may disclose the poor consistency that characterizes these hyperventilation-induced bursts of slow in sequential recordings (90). Similar phenomena may occur in adults, although less frequently (86).

EEG AND PROGNOSIS OF IDIOPATHIC GENERALIZED EPILEPSIES

  1. Top of page
  2. Abstract
  3. THE CONCEPT OF IDIOPATHIC GENERALIZED EPILEPSY AND THE CONVENTION OF THE TERMS GENERALIZED AND FOCAL IN EPILEPSIES AND SEIZURES
  4. EEG CHARACTERISTICS OF IDIOPATHIC GENERALIZED EPILEPSIES
  5. TYPICAL ABSENCES AND MYOCLONIC SEIZURES IN IDIOPATHIC GENERALIZED EPILEPSIES: MORPHOLOGIC AND OTHER CHARACTERISTICS
  6. THE PLACE OF EEG IN THE DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS OF IDIOPATHIC GENERALIZED EPILEPSY
  7. EEG AND PROGNOSIS OF IDIOPATHIC GENERALIZED EPILEPSIES
  8. CONCLUSIVE REMARKS
  9. REFERENCES

Several studies have suggested that EEGs may contribute to the determination of prognosis, but as with its diagnostic yield, there are no gold-standard EEG criteria for remittance or persistence of seizures. The following individual EEG features appear to be of prognostic relevance: children with TAs and occipital intermittent 3 Hz rhythmic delta activity (OIRDA) are less likely to develop GTCS, whereas those with photosensitivity likely will (63,91–94). The occurrence of runs of polyspikes preceding a typical 3 Hz GSW has also been associated with persistence of TA, pharmacoresistance, and evolution to GTCS seizures (32). Myoclonic elements in TA are also associated with a less favorable outcome (91,92). In a series of 139 adults (>16 years of age) with IGE and ictal video EEG studies from St Thomas' Epilepsy clinic, a strong myoclonic component and photosensitivity were inversely associated with outcome. Fourteen of 67 patients with primarily 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 of 51 photosensitive patients became seizure-free, in contrast to 31 of 72 who were not photosensitive. The predictive value of hyperventilation-induced spike-wave activity or TA for outcome is less certain.

Repeat EEG studies may be useful in monitoring the response to treatment particularly in children with TA, as there is a very close correlation between clinical seizure control and electrographic abnormalities (95,96); such a relationship does not exist in other generalized seizures (tonic–clonic or myoclonic) or in partial epilepsies. Video EEG can therefore monitor the effectiveness of treatment and prompt dose adjustments if clinically unnoticeable TA are recorded. Withdrawal of AED therapy is not recommended while the EEG is still abnormal, and a burnt-out photoparoxysmal response may revive. Certainly, the predictive value of EEG is not absolute: GSW activity may persist after clinical recovery, and GTCS may occur in the absence of interictal EEG abnormalities (93).

CONCLUSIVE REMARKS

  1. Top of page
  2. Abstract
  3. THE CONCEPT OF IDIOPATHIC GENERALIZED EPILEPSY AND THE CONVENTION OF THE TERMS GENERALIZED AND FOCAL IN EPILEPSIES AND SEIZURES
  4. EEG CHARACTERISTICS OF IDIOPATHIC GENERALIZED EPILEPSIES
  5. TYPICAL ABSENCES AND MYOCLONIC SEIZURES IN IDIOPATHIC GENERALIZED EPILEPSIES: MORPHOLOGIC AND OTHER CHARACTERISTICS
  6. THE PLACE OF EEG IN THE DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS OF IDIOPATHIC GENERALIZED EPILEPSY
  7. EEG AND PROGNOSIS OF IDIOPATHIC GENERALIZED EPILEPSIES
  8. CONCLUSIVE REMARKS
  9. REFERENCES

In summary, the EEG can

  • • 
    Support the diagnosis of IGE and assist its differential diagnosis from:
    • ○ 
      symptomatic focal epilepsies with fast generalization.
    • ○ 
      symptomatic generalized epilepsy.
  • • 
    Delineate the full clinical picture by video recording of all seizure types and variations, with implications for
    • ○ 
      Syndromic diagnosis.
    • ○ 
      Optimal selection of AED (i.e., clonazepam or levetiracetam when MS are prominent; lamotrigine if TA predominate)
  • • 
    Detect specific triggers or self-induction.
  • • 
    Diagnose nonepileptic conditions that mimic IGEs (i.e., staring attacks or hyperventilation-induced high-voltage rhythmic slowing mimicking TA, or jerks not associated with GSW discharges).
  • • 
    Assist in prognostication.
  • • 
    Monitor AED treatment and predict possible relapse after AED discontinuation (mainly in children with TA).
  • • 
    Detect/confirm new seizure types that may signal either evolution of natural history or adverse effects of AED.
  • • 
    Detect signs of AED intoxication.
  • • 
    Record previously unidentified seizures/interictal patterns/triggers when reconsidering initial diagnosis 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 syndromic diagnosis (GSW do not always indicate IGE, and focal changes do not necessarily suggest a symptomatic focus).
  • • 
    Prognostication and prediction of possible relapse after the discontinuation of AED treatment.

REFERENCES

  1. Top of page
  2. Abstract
  3. THE CONCEPT OF IDIOPATHIC GENERALIZED EPILEPSY AND THE CONVENTION OF THE TERMS GENERALIZED AND FOCAL IN EPILEPSIES AND SEIZURES
  4. EEG CHARACTERISTICS OF IDIOPATHIC GENERALIZED EPILEPSIES
  5. TYPICAL ABSENCES AND MYOCLONIC SEIZURES IN IDIOPATHIC GENERALIZED EPILEPSIES: MORPHOLOGIC AND OTHER CHARACTERISTICS
  6. THE PLACE OF EEG IN THE DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS OF IDIOPATHIC GENERALIZED EPILEPSY
  7. EEG AND PROGNOSIS OF IDIOPATHIC GENERALIZED EPILEPSIES
  8. CONCLUSIVE REMARKS
  9. REFERENCES
  • 1
    First Seizure Trial Group (FIR.S.T. Group). Randomised clinical trial on the efficacy of antiepileptic drugs in reducing the risk of relapse after a first unprovoked tonic- clonic seizure. Neurology 1993;43: 47883.
  • 2
    King MA, Newton MR, Jackson GD, et al. Epileptology of the first-seizure presentation: a clinical, electroencephalographic, and magnetic imaging study of 300 consecutive patients. Lancet 1998;352: 100711.
  • 3
    Hirtz D, Ashwal S, Berg A, et al. Practice parameter: evaluating a first nonfebrile seizure in children: report of the quality standards subcommittee of the American Academy of Neurology, The Child Neurology Society, and The American Epilepsy Society. Neurology 2000;55: 61623.
  • 4
    Gibbs FA, Davis H, Lennox WG. The electroencephalogram in epilepsy and in conditions of impaired consciousness. Arch Neurol Psychiatr 1935;34: 113348.
  • 5
    Gibbs FA, Gibbs EL, Lennox WG. Epilepsy: a paroxysmal cortical dysrhythmia. Brain 1937;60: 37788.
  • 6
    Penfield W, Jasper HH. Epilepsy and the functional anatomy of the human brain. Boston : Little, Brown & Co., 1954.
  • 7
    Gloor P. Generalized cortico-reticular epilepsies. Some considerations on the pathophysiology of generalized bilaterally synchronous spike and wave discharge. Epilepsia 1968;9: 24963.
  • 8
    Chauvel P, Kliemann F, Vignal JP, et al. The clinical signs and symptoms of frontal lobe seizures. Phenomenology and classification. Adv Neurol 1995;66: 11525.
  • 9
    Marcus EM, Watson CW, Simon SA. An experimental model of some varieties of petit mal epilepsy. Electrical-behavioral correlations of acute bilateral epileptogenic foci in cerebral cortex. Epilepsia 1968;9: 23348.
  • 10
    Avoli M, Kostopoulos G. Participation of corticothalamic cells in penicillin-induced generalized spike and wave discharges. Brain Res 1982;247: 15963.
  • 11
    Aliberti V, Grunewald RA, Panayiotopoulos CP, et al. Focal electroencephalographic abnormalities in juvenile myoclonic epilepsy. Epilepsia 1994;35: 297301.
  • 12
    Lombroso CT. Consistent EEG focalities detected in subjects with primary generalized epilepsies monitored for two decades. Epilepsia 1997;38: 797812.
  • 13
    Lancman ME, Asconape JJ, Golimstok A. Circling seizures in a case of juvenile myoclonic epilepsy. Epilepsia 1994;35: 3178.
  • 14
    Lancman ME, Asconape JJ, Penry JK. Clinical and EEG asymmetries in juvenile myoclonic epilepsy. Epilepsia 1994;35: 3026.
  • 15
    Aguglia U, Gambardella A, Le Piane E, et al. Idiopathic generalized epilepsies with versive or circling seizures. Acta Neurol Scand 1999;99: 21924.
  • 16
    Kiley MA, Smith SJ, Sander JW. Idiopathic generalized epilepsy presenting with hemiconvulsive seizures. Epilepsia 2000;41: 16336.
  • 17
    So EL, King DW, Murvin AJ. Misdiagnosis of complex absence seizures. Arch Neurol 1984;41: 6401.
  • 18
    Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981;22: 489501.
  • 19
    Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30: 38999.
  • 20
    Raymond AA, Fish DR, Sisodiya SM, et al. Abnormalities of gyration, heterotopias, tuberous sclerosis, focal cortical dysplasia, microdysgenesis, dysembryoplastic neuroepithelial tumour and dysgenesis of the archicortex in epilepsy. Clinical, EEG and neuroimaging features in 100 adult patients. Brain 1995;118: 62960.
  • 21
    Giza CC, Kuratani JD, Cokely H, et al. Periventricular nodular heterotopia and childhood absence epilepsy. Pediatr Neurol 1999;20: 3158.
  • 22
    Li LM, Donoghue MF, Smith SJM. Outcome of epilepsy surgery in patients with temporal lobe epilepsy associated with 3-4Hz generalized spike and wave discharges. J Epilepsy 1996;9: 2104.
  • 23
    Koutroumanidis M, Hennessy MJ, Elwes RD, et al. Coexistence of temporal lobe and idiopathic generalized epilepsies. Neurology 1999;53: 4905.
  • 24
    Binnie CD. Regional manifestation of idiopathic epilepsy. An electrophysiological view. In: WolfP, ed. Epileptic seizures and syndromes. London : John Libbey and Co, 1994: 2701.
  • 25
    Delgado-Escueta AV, Greenberg D, Weissbecker K, et al. Gene mapping in the idiopathic generalized epilepsies: juvenile myoclonic epilepsy, childhood absence epilepsy, epilepsy with grand mal seizures, and early childhood myoclonic epilepsy. Epilepsia 1990;31(suppl 3):S1929.
  • 26
    Penry JK, Porter RJ, Dreifuss RE. Simultaneous recording of absence seizures with video tape and electroencephalography. A study of 374 seizures in 48 patients. Brain 1975;98: 42740.
  • 27
    Stefan H, Burr W, Hinderbrand D, et al. In: KazamatsuriH, SeinoM, WardAA, eds. Advances in epileptology: the 13th Epilepsy International Symposium. New York : Raven Press, 1982: 198255.
  • 28
    Panayiotopoulos CP, Obeid T, Waheed G. Differentiation of typical absence seizures in epileptic syndromes. A video EEG study of 224 seizures in 20 patients. Brain 1989;112: 103956.
  • 29
    Agathonikou A, Panayiotopoulos CP, Giannakodimos S, et al. Typical absence status in adults: diagnostic and syndromic considerations. Epilepsia 1998;39: 126576.
  • 30
    Panayiotopoulos CP, Chroni E, Daskalopoulos C, et al. Typical absence seizures in adults: clinical, EEG, video-EEG findings and diagnostic/syndromic considerations. J Neurol Neurosurg Psychiatry 1992;55: 10028.
  • 31
    Panayiotopoulos CP, Koutroumanidis M, Giannakodimos S, et al. Idiopathic generalized epilepsy in adults manifested by phantom absences, generalized tonic-clonic seizures, and frequent absence status. J Neurol Neurosurg Psychiatry 1997;63: 6227.
  • 32
    Michelucci R, Rubboli G, Passarelli D, et al. Electroclinical features of idiopathic generalized epilepsy with persisting absences in adult life. J Neurol Neurosurg Psychiatry 1996;61: 4717.
  • 33
    Marini C, King MA, Archer JS, et al. Idiopathic generalized epilepsy of adult onset: clinical syndromes and genetics. J Neurol Neurosurg Psychiatry 2003;74: 1926.
  • 34
    Cutting S, Lauchheimer A, Barr W, et al. Adult-onset idiopathic generalized epilepsy: clinical and behavioral features. Epilepsia 2001;42: 13958.
  • 35
    Koutroumanidis M, Panayiotopoulos CP. Reflex seizures and reflex epilepsies. In: WallaceSJ, FarrellK, eds. Epilepsy in children. London : Arnold , 2004: 2004243.
  • 36
    Wilkins AJ, Darby CE, Binnie CD. Neurophysiological aspects of pattern-sensitive epilepsy. Brain 1979;102: 125.
  • 37
    Ferrie CD, De Marco P, Grunewald RA, et al. Video game induced seizures. J Neurol Neurosurg Psychiatry 1994;57: 92531.
  • 38
    Wilkins AJ, Zifkin B, Andermann F, et al. Seizures induced by thinking. Ann Neurol 1982;11: 60812.
  • 39
    Goossens LA, Andermann F, Andermann E, et al. Reflex seizures induced by calculation, card or board games, and spatial tasks: a review of 25 patients and delineation of the epileptic syndrome. Neurology 1990;40: 11716.
  • 40
    Wolf P. Reading epilepsy. In: RogerJ, BureauM, DravetC, et al., eds. Epileptic syndromes in infancy, childhood and adolescence. London : John Libbey & Company, 1992: 1992281.
  • 41
    Radhakrishnan K, Silbert PL, Klass DW. Reading epilepsy. An appraisal of 20 patients diagnosed at the Mayo Clinic, Rochester, Minnesota, between 1949 and 1989, and delineation of the epileptic syndrome. Brain 1995;118: 7589.
  • 42
    Koutroumanidis M, Koepp MJ, Richardson MP, et al. The variants of reading epilepsy. A clinical and video-EEG study of 17 patients with reading-induced seizures. Brain 1998;121: 140927.
  • 43
    Panayiotopoulos CP, Jeavons PM, Harding GF. Occipital spikes and their relation to visual responses in epilepsy, with particular reference to photosensitive epilepsy. Electroencephalogr Clin Neurophysiol 1972;32: 17990.
  • 44
    Wilkins AJ, Andermann F, Ives J. Stripes, complex cells and seizures. An attempt to determine the locus and nature of the trigger mechanism in pattern-sensitive epilepsy. Brain 1975;98: 36580.
  • 45
    Binnie CD, Wilkins AJ, De Korte RA. Interhemispheric differences in photosensitive epilepsy. II. Intermittent photic stimulation. Electroencephalogr Clin Neurophysiol 1981;52: 46972.
  • 46
    Ramani V. Reading epilepsy. Adv Neurol 1998;75: 24162.
  • 47
    Jeavons PM, Harding GF, Panayiotopoulos CP, et al. The effect of geometric patterns combined with intermittent photic stimulation in photosensitive epilepsy. Electroencephalogr Clin Neurophysiol 1972;33: 2214.
  • 48
    Gowers WR. Epilepsies and other chronic convulsive diseases. Their causes, symptoms and treatment. London : Churchill JA , 1881.
  • 49
    Janz D. ‘Aufwach’-epilepsien (als ausdruckeinerden ‘nacht’-oder ‘schlaf’-epilepsien gegenuberzustellenden verlaufsform epileptischer erkrankungen). Arch Z Neurol 1953;7398.
  • 50
    Janz D. Epilepsy with grand mal on awakening and sleep-waking cycle. Clin Neurophysiol 2000;111(suppl 2):S10310.
  • 51
    Niedermeyer E. Concerning the release mechanism of seizure potentials in central encephalytic epilepsy. [German]. Nervenarzt 1967;38: 724.
  • 52
    Terzano MG, Mancia D, Salati MR, et al. The cyclic alternating pattern as a physiologic component of normal NREM sleep. Sleep 1985;8: 13745.
  • 53
    Terzano MG, Parrino L, Anelli S, et al. Modulation of generalized spike-and-wave discharges during sleep by cyclic alternating pattern. Epilepsia 1989;30: 77281.
  • 54
    Gigli GL, Calia E, Marciani MG, et al. Sleep microstructure and EEG epileptiform activity in patients with juvenile myoclonic epilepsy. Epilepsia 1992;33: 799804.
  • 55
    Fountain NB, Kim JS, Lee SI. Sleep deprivation activates epileptiform discharges independent of the activating effects of sleep. J Clin Neurophysiol 1998;15: 6975.
  • 56
    Halasz P, Filakovszky J, Vargha A, et al. Effect of sleep deprivation on spike-wave discharges in idiopathic generalized epilepsy: a 4 x 24 h continuous long term EEG monitoring study. Epilepsy Res 2002;51: 12332.
  • 57
    Nicolaides P, Appleton RE, Beirne M. EEG requests in paediatrics: an audit. Arch Dis Child 1995;72: 5223.
  • 58
    Fowle AJ, Binnie CD. Uses and abuses of the EEG in epilepsy. Epilepsia 2000;41(suppl 3):S108.
  • 59
    Genton P. When antiepileptic drugs aggravate epilepsy. Brain Dev 2000;22: 7580.
  • 60
    Lennox WG, Lennox MA. Epilepsy and related disorders. Boston : Little, Brown & Co., 1960.
  • 61
    Hirsch E, Marescaux C. What are the relevant criteria for a better classification of epileptic syndromes with typical absences? In: MalafosseA, GentonP, HirschE, et al., eds. Idiopathic generalized epilepsies. London : John Libbey & Company Ltd, 1994: 199487.
  • 62
    Loiseau P, Duche B. Childhood absence epilepsy. In: DuncanJS, PanayiotopoulossCP, eds. Typical absences and related epileptic syndromes. London : Churchill Communications Europe , 1995: 1995152.
  • 63
    Cobb WA, Gordon N, Matthews SC, et al. The occipital delta rhythm in petit mal. Electroencephalogr Clin Neurophysiol 1961;13: 1423.
  • 64
    Wolf P, Inoue Y. Therapeutic response of absence seizures in patients of an epilepsy clinic for adolescents and adults. J Neurol 1984;231: 2259.
  • 65
    Panayiotopoulos CP, Ferrie CD, Koutroumanidis M, et al. Idiopathic generalized epilepsy with phantom absences and absence status in a child. Epileptic Disord 2001;3: 636.
  • 66
    Wolf P, Inoue Y. Complex reflex epilepsies: reading epilepsy and praxis induction. In: RogerJ, BureauM, DravetC, et al., eds. Epileptic syndromes in infancy, childhood and adolescence. Eastleigh , UK : John Libbey & Co Ltd, 2004: 2004315.
  • 67
    Dravet C, Bureau M. Benign myoclonic epilepsy in infancy. In: RogerJ, BureauM, DravetC, et al, eds. Epileptic syndromes in infancy, childhood and adolescence. 3rd ed. London : John Libbey & Co Ltd, 2002: 200269.
  • 68
    Panayiotopoulos CP, Agathonikou A, Koutroumanidis M, et al. Eyelid myoclonia with absences: the symptoms. In:DuncanJS, PanayiotopoulosCP, eds. Eyelid myoclonia with absences. London : John Libbey & Company Ltd, 1996: 199617.
  • 69
    Appleton RE, Panayiotopoulos CP, Acomb BA, et al. Eyelid myoclonia with typical absences: an epilepsy syndrome. J Neurol Neurosurg Psychiatry 1993;56: 13126.
  • 70
    Giannakodimos S, Panayiotopoulos CP. Eyelid myoclonia with absences in adults: a clinical and video- EEG study. Epilepsia 1996;37: 3644.
  • 71
    Panayiotopoulos CP, Giannakodimos S, Agathonikou A, et al. Eyelid myoclonia is not a manoeuvre for self-induced seizures in eyelid myoclonia with absences. In: DuncanJS, PanayiotopoulosCP, eds.Eyelid myoclonia with absences. London : John Libbey & Company Ltd, 1996: 199693.
  • 72
    Binnie CD. Differential diagnosis of eyelid myoclonia with absences and self-induction by eye closure. In: DuncanJS, PanayiotopoulosCP, eds. Eyelid myoclonia with absences. London : John Libbey & Company Ltd, 1996: 8992.
  • 73
    Ames FR. “Self-induction” in photosensitive epilepsy. Brain 1971;94: 78198.
  • 74
    Andermann K, Berman S, Cooke PM, et al. Self-induced epilepsy. A collection of self-induced epilepsy cases compared with some other photoconvulsive cases. Arch Neurol 1962;6: 4965.
  • 75
    Binnie CD, Darby CE, De Korte RA, et al. Self-induction of epileptic seizures by eye closure: incidence and recognition. J Neurol Neurosurg Psychiatry 1980;43: 3869.
  • 76
    Panayiotopoulos CP, Ferrie CD, Giannakodimos S, et al. Perioral myoclonia with absences: a new syndrome. In: WolfP, ed. Epileptic seizures and syndromes. London : John Libbey & Company Ltd, 1994: 14353.
  • 77
    Bureau M, Tassinari AC. The syndrome of myoclonic absences. In: RogerJ, BureauM, DravetC, et al., eds. Epileptic syndromes in infancy, childhood and adolescence. 3rd ed. Eastleigh , UK : John Libbey & Co, Ltd, 2002: 30512.
  • 78
    Christian W. Bioelectrical characteristics of daily periodic forms of the course of epileptic diseases. Dtsch Z Nervenheilkd 1960;181: 41344.
  • 79
    Christian W. The sleeping-waking period in sleeping-waking epilepsy. Nervenarzt 1961;32: 26675.
  • 80
    Ajmone MC, Lewis WR. Pathologic findings in patients with “centrencephalic” electroencephalographic patterns. Neuropsihijatrija 1960;10: 92230.
  • 81
    Tukel K, Jasper H. The electroencephalogram in parasagittal lesions. Electroencephalogr Clin Neurophysiol Suppl 1952;4: 48194.
  • 82
    Klass DW. Electroencephalographic manifestations of complex partial seizures. Adv Neurol 1975;11: 11340.
  • 83
    Blume WT, Pillay N. Electrographic and clinical correlates of secondary bilateral synchrony. Epilepsia 1985;26: 63641.
  • 84
    Ajmone-Marsan C, Lewis WR. Pathologic findings in patients with “centroencephalic” electroencephalographic patterns. Neurology 1960;10: 92230.
  • 85
    Daly DD. Epilepsy and syncope. Secondary bilateral synchrony. In: DalyDD, PedleyTA, eds. Current practice of clinical electroencephalography. 2nd ed.. Philadelphia , PA : Lippincott-Raven, 1997: 3101.
  • 86
    Kellaway P. An orderly approach to visual analysis: characteristics of the normal EEG of adults and children. In: DaleyDD, PedleyTA, eds. Clinical practice of clinical electroencephalography. 2nd ed. Philadelphia , PA : Lippincott-Raven, 1997: 13999.
  • 87
    Epstein MA, Duchowny M, Jayakar P. Altered responsiveness during hyperventilation-induced EEG slowing: a non-epileptic phenomenon in normal children. Epilepsia 1994;35: 12047.
  • 88
    Lee SI, Kirby D. Absence seizure with generalized rhythmic delta activity. Epilepsia 1988;29: 2627.
  • 89
    Engel GL, Ferris EB, Logan M. Hyperventilation: analysis of clinical symptomatology. Ann Intern Med 1947;27: 683704.
  • 90
    Lum LM, Connolly MB, Farrell K, et al. Hyperventilation - induced high-amplitude rhythmic slowing with altered consciousness: a video-EEG comparison with absence seizures. Epilepsia 2002;43: 13728.
  • 91
    Loiseau P, Pestre M, Dartigues JF, et al. Long-term prognosis in two forms of childhood epilepsy: typical absence seizures and epilepsy with rolandic (centrotemporal) EEG foci. Ann Neurol 1983;13: 6428.
  • 92
    Sato S, Dreifuss FE, Penry JK. Prognostic factors in absence seizures. Neurology 1976;26: 78896.
  • 93
    Hedstrom A, Olsson I. Epidemiology of absence epilepsy: EEG findings and their predictive value. Pediatr Neurol 1991;7: 1004.
  • 94
    Covanis A, Skiadas K, Loli N, et al. Absence epilepsy: early prognostic signs. Seizure 1992;1: 2819.
  • 95
    Duncan JS. Antiepileptic drugs and the electroencephalogram. Epilepsia 1987;28: 25966.
  • 96
    Appleton RE, Beirne M. Absence epilepsy in children: the role of EEG in monitoring response to treatment. Seizure 1996;5: 1478.
  • 97
    Koutroumanidis M, Martin-Miguel C, Hennessy MJ, et al. Interictal temporal delta activity in temporal lobe epilepsy: correlations with pathology and outcome. Epilepsia 2004;45: 135167.