Figure 8-1.
Carbamazepine-Induced Myoclonic Seizure. A 3-year-old boy with a history of GTCS who developed frequent myoclonic jerks and drop attacks 2 weeks after starting the treatment with carbamazepine (CBZ). Ictal EEG during one of his myoclonic seizures shows a burst of generalized polyspike-and-slow-wave discharge followed by a brief diffuse electrodecrement and 5-Hz theta slowing. Myoclonic seizures and drop attacks disappeared 2 days after stopping CBZ.
CBZ is the most common antiepileptic drug (AED) causing AED-induced seizure worsening. CBZ can both aggravate and induce new seizure types including absence, atonic, or myoclonic seizures in patients with generalized epilepsies. Vigabatrin and gabapentin have been found to induce absence and myoclonic seizures. Benzodiazepines have been reported to precipitate tonic seizures in patients with Lennox–Gastaut syndrome. Lamotrigine has been reported to worsen myoclonic, clonic, and tonic-clonic seizures in the patients with Dravet syndrome.1–3 Therefore, “AED-induced seizure worsening” must be considered in all patients whose seizures are worse with the introduction of the new AED.
Figure 8-2.
Generalized Tonic-Clonic Seizure (GTCS). A 14-year-old girl with a history of idiopathic generalized epilepsy (IGE). EEG shows recruiting rhythm described as rhythmic generalized alpha and theta frequency activity. Approximately 22 sec into the seizure, the background activity becomes obscured by myogenic artifact (arrow head) during generalized tonic stiffening.
Figure 8-3.
Generalized Tonic-Clonic Seizure (GTCS). (Continued) The fast spike activity characterizes the tonic phase of GTCS. However, the background EEG activity becomes almost completely obscured by myogenic artifact during the tonic posturing. Digital high-frequency filter of myogenic artifact or EEG performed during paralyzing with muscle relaxant allows visualization of the EEG activity.
Figure 8-4.
Generalized Tonic-Clonic Seizure (GTCS). (Continued) During the clonic phase of GTCS, the fast spike activity becomes discontinuous and is replaced by high-voltage generalized polyspike-wave activity with polyspikes corresponding with clonic jerks and brief relaxation with slow waves. Immediately after the seizure stops, markedly generalized background suppression is noted. Very irregular diffuse slow-wave activity then follows and may last for minutes. In patients with secondarily GTCS, asymmetric postictal slowing can be a very important lateralizing sign.
Figure 8-5.
Tonic Phase of Generalized Tonic-Clonic Seizure; (Subdural EEG Recording). Subdural EEG allows visualization of the EEG activity during tonic phase of generalized tonic-clonic seizure without myogenic artifact. EEG shows 4-Hz spike-wave activity during tonic posturing. Tonic and clonic phase of GTCS share similar EEG finding of spike-wave activity but with different duration of relaxation (slow wave). Note myogenic artifact in the EKG channel that represents muscle contraction during the tonic phase of GTCS (lowest channel).
▪ Carbamazepine (CBZ) is the most common antiepileptic drug (AED).
▪ CBZ can both aggravate and induce new seizure types including absence, atonic, or myoclonic seizures (MS) in patients with generalized epilepsies.
▪ Vigabatrin and gabapentin have been found to induce absence and MS.
▪ Benzodiazepines have been reported to precipitate tonic seizures, especially when given intravenously in patients with Lennox-Gastaut syndrome.
▪ Lamotrigine has been reported in worsening myoclonic, clonic, and tonic-clonic seizures in the patients with Dravet syndrome.
▪ AED-induced seizure worsening must be considered in all patients whose seizures are worse with the introduction of the new AED.
(Figures 8-6, 8-7, 8-16, 8-18)
Figure 8-6.
Occipital Intermittent Rhythmic Delta Activity (OIRDA); Idiopathic Generalized Epilepsy. A 9-year-old girl with a history of GTCS whose seizures were aggravated by increasing dose of carbamazepine. EEG demonstrates intermittently bisynchronous rhythmic delta activity, maximally expressed in the posterior head regions, which are attenuated with eye opening (arrow).
OIRDA is seen almost exclusively in children and is associated with epilepsy, most commonly in idiopathic generalized epilepsy, especially absence epilepsy.4,5
Figure 8-7.
Occipital Intermittent Rhythmic Delta Activity (OIRDA); Idiopathic Generalized Epilepsy. (Same EEG recording as in Figure 8-6) The patient developed a staring episode with mild jerking of his body and upper extremities accompanied by generalized irregular 3-Hz spike-wave activity. This EEG confirms that OIRDA represents epileptiform activity.
▪ Seen almost exclusively in children and is associated with epilepsy, most commonly in idiopathic generalized epilepsy (IGE), especially absence epilepsy.
(Figures 8-8 and 8-42)
Figure 8-8.
Generalized Paroxysmal Fast Activity (GPFA); Idiopathic Generalized Epilepsy (IGE). A 10-year-old boy who started having his first seizure after TBI at 3 years of age. He did well until 9 years of age, when he started having breakthrough seizures consisting of GTCS and myoclonic seizures. He is otherwise normal. Brain MRI was normal. Interictal EEG 3 days after the last GTCS shows very frequent bursts of generalized paroxysmal fast activity (GPFA).
GPFA, occurring almost exclusively during sleep, is generated in neocortex. Activation of thalamic neurons in response to varying corticothalamic input patterns may be critical in setting the oscillation frequency of thalamocortical network interactions causing GPFA.6,7 Seventy-five percent of patients had clinical seizures associated with this activity, mostly tonic. Slow spike-and-wave complexes were present in half of the patients. Twenty-five percent of patients had normal background activity.8
▪ Occurring almost exclusively during sleep. It is generated in the neocortex. Activation of thalamic neurons in response to varying corticothalamic input patterns may be critical in setting the oscillation frequency of thalamocortical network interactions causing GPFA.
▪ Seventy-five percent of patients had clinical seizures associated with this activity, mostly tonic.
▪ Slow spike-and-wave complexes were present in half of the patients. Twenty-five percent of patients had normal background activity.
(Figures 8-9 and 8-10)
Figure 8-9.
Eye Closure Sensitivity (ECS); Juvenile Myoclonic Epilepsy (JME). A 14-year-old girl with a history of multiple types of seizures including absence, myoclonic, and generalized tonic-clonic seizure (GTCS). GTCS occurs exclusively within the first 1 hour after awakening. She was seizure free with lamotrigine but developed recurrent seizures after medication withdrawal. EEG shows generalized 4-Hz spike-and-wave activity consistently activated by eye closure.
ECS is more common in females. It may overlap with photosensitivity but is independent from photosensitivity. ECS can activate polyspike-wave discharges and myoclonic jerks. It can be seen in different epileptic syndromes including childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), eyelid myoclonia with absences (EMA), juvenile myoclonic epilepsy (JME), idiopathic generalized epilepsy (IGE with tonic-clonic seizure), generalized epilepsy with grand mal upon awakening GMA, and idiopathic occipital lobe epilepsy.9–11 REM sleep, similar to eye opening, plays a role in inhibiting EEG manifestations of JME with eye closure sensitivity.12
Figure 8-10.
Epilepsy with Grand Mal on Awakening (GMA); Eye Closure Sensitivity (ECS). A 17-year-old girl with a history of three GTCSs occurring exclusively within the first 1 hour after awakening at ages 13, 15, and 17. There were no other types of seizures. She was seizure free with lamotrigine for 2 years but developed recurrent seizures after medication withdrawal. EEG shows generalized 4 Hz (poly)spike-and-wave discharges activated by eye closure.
GTCS of epilepsy with grand mal on awakening (EGMA) occurs exclusively shortly after awakening. The second seizure peak is in the evening corresponding to the peak period of relaxation. Typical absences and myoclonic jerks occur in 10% and 22%, respectively. The majority of patients with EGMA have rare GTCS. Sleep deprivation is a major triggering factor.
The EEG of patients with GMA shows generalized (poly)spike-and-wave discharges on their first routine EEG in 44%, normal routine EEG but generalized (poly)spike-and-wave discharges on sleep EEG only in 32%, and no EEG abnormality at all in 24%.13 About 70% of those with additional absences or myoclonic jerks preceding GTCSs have generalized (poly)spike-and-wave discharges.14 A 24-hour video-EEG should be considered in patients suspected to have GMA. It is necessary to include sleep and awakening in the record.
▪ More common in females.
▪ It may overlap with but is independent from photosensitivity.
▪ ECS can activate polyspike-wave (PSW) discharges and myoclonic jerks (MJ).
▪ It can be seen in different epileptic syndromes including childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), eyelid myoclonia with absences (EMA), juvenile myoclonic epilepsy (JME), idiopathic generalized epilepsy (IGE with
▪ tonic-clonic seizure), generalized epilepsy with grand mal upon awakening (EGMA), and idiopathic occipital lobe epilepsy.
▪ Rapid eye movement (REM) sleep, similarly to eye opening, plays a role in inhibiting EEG manifestations of JME with ECS.
(Figures 8-2 to 8-5, 8-10, and 8-13)
▪ Occurs exclusively shortly after awakening.
▪ The second seizure peak is in the evening during the peak period of relaxation.
▪ Typical absences and MJ occur in 10% and 22% of EGMA, respectively. Majority of patients with EGMA have rare generalized tonic-clonic seizure (GTCS).
▪ Sleep deprivation is a major triggering factor.
▪ Generalized (poly)spike-and-wave discharges on their first routine electroencephalography (EEG) in 44%.
▪ Normal routine EEG but generalized (poly)spike-and-wave discharges on sleep EEG only in 32%.
▪ No EEG abnormality at all in 24%.
▪ About 70% of those with additional absences or MJs preceding GTCSs have generalized (poly)spike-and-wave discharges.
▪ A 24-hour video-EEG should be considered in patients suspected of having GMA and should include sleep and awakening.
▪ Tonic phase: Brief period of diffuse background attenuation with superimposed low-voltage fast activity or spikes. These activities become more synchronized, with increases in spiky configuration and decreases in frequency and amplitude (into 10 Hz activity called “Epileptic recruiting rhythm”)
▪ Clonic phase: Repetitive polyspike-slow-wave complexes interupt the 10-Hz fast activity in tonic phase. Subsequently, the amplitude increases and the polyspike-slow-wave complexes slow down to 1 Hz. The clonic jerks coreespond to the polyspikes, whereas the periodic atonia corresponds to the slow waves.
▪ Postictal period: Diffuse background suppression, bursts suppression, or triphasic wave pattern followed by diffuse polymorphic delta activity. Higher amplitude, faster frequency, and more rhythmic activity are noted as the patients recovers. Normal background activity may not be observed for 30 minutes to 24 hours. In children less than 6 years of age, bilateral occipital delta slowing is commonly seen.
(Figures 8-9, 8-11, 8-12 and 8-14)
Figure 8-11.
Juvenile Myoclonic Epilepsy (JME). A 17-year-old girl with JME. The patient was asked by an EEG technologist to count during frequent bursts of generalized polyspike-wave discharges. She skipped counting the number “19” during the burst of generalized 4- to 4.5-Hz polyspike-wave activity that lasted for only 1–1.5 sec. No visible jerk was noted during the burst.
As early as 0.5 sec after their onset of (poly)spike-wave discharges, the majority of patients will show inattention,15 suggesting that very short-lasting spells of a second or less may have a cognitive effect on the patient.16
Figure 8-12.
Juvenile Myoclonic Epilepsy (JME); Myoclonic Seizures. A 15-year-old girl with JME. EEG during myoclonic jerks (MJ) of the right arm (*) shows symmetrically bilateral synchronous polyspike-wave discharges time-locked with the jerk followed by 2-sec bilateral synchronous, 3-Hz polyspike-wave discharges, and a subsequent diffuse electrodecremental event.
A typical ictal EEG in myoclonic seizure is bilateral synchronous and symmetric polyspike-wave discharge, immediately preceding a myoclonic jerk. The polyspike component contains 5–20 spikes, with a frequency between 12 and 16 Hz. The amplitude of spikes is typically increasing and is maximal over the frontal leads where it reaches 200–300 μV. Slow waves of variable frequency (3–4 Hz) and amplitude (200–350 μV) often precede or follow the polyspikes that result in a polyspike-wave complex that lasts much longer than the MJ (approximately 2–4 sec). The number of spikes is associated with the MJ intensity: there are fewer spikes and a more pronounced slow component when the MJ is mild. Back averaging shows that the conduction time, between the apex of the spike and the onset of the MJ, is short (20–50 msec) and characteristic of a cortical myoclonus.17
Figure 8-13.
Epilepsy with Grand Mal on Awakening (GMA); Photoparoxysmal Response (PPR). (Same recording as in Figure 8-12) EEG shows photoparoxysmal response during photic stimulation. GMA is positively correlated, and grand mal during sleep negatively correlated with photosensitivity.
Figure 8-14.
Juvenile Myoclonic Epilepsy (JME); Photoparoxysmal Response (PPR). EEG of a 15-year-old girl with JME. EEG during photic stimulation reveals photoparoxysmal response (PPR) with no clinical accompaniment.
PPR is described as generalized irregular spike/polyspike-and-wave complexes during photic stimulation. PPRs are seen in 30–40% of JME patients, compared to 18% in absence epilepsy.9 However, only 5% of patients suffer from clinical photosensitivity.18 Seventy-seven percent of patients with PPR have a history of epilepsy.19 In patients with seizures, a generalized PPR strongly suggests the diagnosis of primary generalized epilepsy.20
▪ JME is characterized by:
▸ MJs on awakening
▸ GTCS in all states.
▸ Typical absence in most patients
▪ Precipitating factors include sleep deprivation, fatigue, and alcohol intake.
▪ Generalized fast (4- to 6-Hz) PSW activity.
▪ Focal epileptiform activity is seen in about one third causing “pseudolateralization.”
▪ As early as 0.5 sec after the onset of (poly)spike-wave discharges, the majority of patients will show inattention, suggesting that very short-lasting spells of a second or less may have a cognitive effect on the patient.
▪ The typical ictal EEG in myoclonic seizure (MS) is a bilateral synchronous and symmetric PSW discharge, immediately preceding a MJ. The polyspike component contains 5–20 spikes, with a frequency between 12 and 16 Hz. The amplitude of spikes is typically increasing and maximal over the frontal leads where it reaches 200–300 μV. Slow waves of variable frequency (3–4 Hz) and amplitude (200–350 μV) often precede or follow the polyspikes, this results in a PSW complex that lasts much longer than the MJ (approximately 2–4 sec). The number of spikes is associated with the MJ intensity: there are few spikes and a more pronounced slow component when the MJ is mild.
▪ Back averaging shows that the conduction time, between the apex of the spike and the onset of the MJ, is short (20–50 msec) and characteristic of a cortical myoclonus.
▪ Ictal EEG during absence seizure in JME is different from CAE or JAE in that it consists of polyspike/double/triple preceding or superimposed on the slow waves with a frequency varying from 2 to 10 Hz with a mean of 3–5 Hz.
▪ Photoparoxysmal response (PPR) is described as generalized irregular spike/polyspike-and-wave complexes during photic stimulation.
▪ PPRs are seen in 30–40% in JME, compared to 18% in absence epilepsy. However, only 5% of patients suffer from clinical photosensitivity. Seventy-seven percent of patients with PPR have a history of epilepsy.
▪ In patients with seizures, a generalized PPR strongly suggests the diagnosis of primary generalized epilepsy.
(Figures 8-15 to 8-20)
Figure 8-15.
Childhood Absence Epilepsy (CAE). A 6-year-old boy with poor school performance and recurrent staring episodes.
Inclusion criteria for CAE are (1) onset at 4 -10 years (peak at 5–7), (2) normal neurological condition, (3) brief (4–20 sec) and frequent (tens per day) absence seizures with abrupt and severe impairment of consciousness, (4) EEG ictal discharges of generalized high-voltage spike and double (occasionally triples are allowed) spike-and-slow-wave complexes. They are rhythmic at about 3 Hz with a gradual and regular slowdown from the initial to the terminal phase of the discharge. Exclusion criteria for CAE are: (1) other types of seizure prior to or during the active stage of absence; (2) eyelid myoclonia, perioral myoclonia, rhythmic massive limb jerking, and single or arrhythmic myoclonic jerks —however, mild myoclonic elements of the eyes, eyebrows, and eyelids may be featured, particularly in the first 3 sec of the absence seizure; (3) mild or no impairment of consciousness during the 3- or 4-Hz discharges; (4) brief EEG 3- or 4-Hz spike-wave paroxysms of <4 sec, polyspikes (more than three), or ictal discharge fragmentations; and (5) visual (photic) and other sensory precipitation of clinical seizures.21
Figure 8-16.
Occipital Intermittent Rhythmic Delta Activity (OIRDA) and Generalized 3/sec Spike-Wave Activity; Childhood Absence Epilepsy. A 7-year-old boy with a recent diagnosis of childhood absence epilepsy. EEG during hyperventilation demonstrates both occipital intermittent rhythmic delta activity (OIRDA) (open arrow) and generalized 3/sec spike-wave activity (double arrows) in the same recording. The patient has been seizure free with ethosuximide.
OIRDA was first described in 1983 and was concluded to only be seen in children and not found to be helpful in diagnosing a seizure disorder or structural abnormality.22 Subsequent publications show that OIRDA is seen almost exclusively in children with epilepsy and it is rarely seen in children with diffuse encephalopathy. OIRDA is seen almost exclusively in children, less than 10–15 years old, and is associated with epilepsy, most commonly in idiopathic generalized epilepsy, especially absence epilepsy and, less commonly, in focal epilepsy.23–25
Figure 8-17.
Childhood Absence Epilepsy; Diffuse Rhythmic Delta Activity During Absence Seizure. A 12-year-old girl with a history of childhood absence epilepsy (CAE) in remission who presented with syncope. EEG during hyperventilation (HV) shows diffuse rhythmic 3-Hz delta activity with fronto-central predominance. Approximately 10 sec into the HV, the patient developed clinical absence seizures described as staring off, unresponsiveness, motionless, and lip smacking. The patient started moving immediately when the diffuse delta activity stopped. No postictal state is noted.
Diffuse 3-Hz rhythmic delta activity without spike component is an exceptional ictal EEG finding during an absence seizure.
Figure 8-18.
Asymmetric OIRDA; Childhood Absence Epilepsy. An 8-year-old boy with recurrent absence seizures after stopping ethosuximide. EEG shows an asymmetric, bilateral synchronous occipital rhythmic 2.5- to 3.5-Hz delta activity with shifting predominance between left and right hemispheres. The patient was seizure free again after ethosuximide was reintroduced.
OIRDA is found in children. Because it is age dependent, maturational factors probably play a role in the expression of OIRDA in children with epilepsy. OIRDA is not commonly associated with encephalopathy. It is more closely related to temporal intermittent rhythmic delta activity (TIRDA) than to FIRDA.4 OIRDA is seen during wakefulness and probably an epileptiform pattern. OIRDA is seen in absence and generalized tonic-clonic seizures. Its electrographic characteristics appear to differ between localization-related epilepsy and primary generalized epilepsy, particularly absence seizures. The frequency of the occipital rhythmic discharges in children with absences was generally faster (3–4 Hz) than in localization-related epilepsy (2–3 Hz).25
Figure 8-19.
Symptomatic Absence Seizure and ESES; Thalamic Heterotopia. A 6-year-old boy with intractable absence epilepsy and cognitive dysfunction caused by right thalamic heterotopia (arrow). Complete resection of heterotopia resulted in seizure freedom.
Alterations in normal thalamocortical reciprocal interactions are critical in the generation of the regular generalized spike-wave discharges (GSWD).26 Most patients with unilateral thalamic lesion and epilepsy showed GSWD.27–31 Absence status with GSWD caused by ischemic lesion in the left thalamus have been reported.27 Lesions of the inferior-medial-posterior thalamic structures might have a role in the pathogenesis of GSWD and ESES.29
Gray matter heterotopia is caused by a halt in neuronal radial migration.32 Although gray matter heterotopia is commonly associated with refractory epilepsy, it is still uncertain what role heterotopic lesions play in seizure onset and propagation and whether they are epileptogenic. Intracranial EEG investigations showed that seizures are generated sometimes by heterotopias, sometimes by distant cortex, or sometimes by both. However, neither the removal of the lesion alone nor mesial temporal resections lead to a favorable outcome, suggesting a more widespread epileptogenic network in these patients. Seizure onset in a heterotopia is sometimes completely outside the lesion and sometimes has an overlap with the lesion. The heterotopia is part of more complex circuitry involving the surrounding and distant cerebral cortex.33,34 High-frequency oscillations (HFOs), especially fast ripples, are closely linked to seizure-onset areas. In focal cortical dysplasia and sometimes in heterotopia, HFOs occur in lesional areas that are not part of the seizure onset zone, and they may indicate potential epileptogenicity of these lesions.35–37
Figure 8-20.
Jeavons Syndrome (Eyelid Myoclonia with Absence). A 2-year-old boy who developed absence seizures at 18 months of age. He also had GTCS, myoclonic seizures, and tooth brushing-induced seizure. He was also noted to have “eyelid myoclonia” during prolonged video-EEG monitoring. EEG shows 3-Hz polyspike-wave (PSW) discharges associated with eyelid myoclonic and absence seizure.
Jeavons syndrome is refers to idiopathic reflex epilepsy with eyelid myoclonia, eye-closure sensitive seizure, and photosensitivity. Seizures are brief (3–6 sec). Ictal EEG consists of generalized PSW at 3–6 Hz, usually occurring after eye closure. Eyelid myoclonia is resistant to treatment.38
▪ Age at onset between 4 and 10 years (peak at 5–7 years).
▪ Normal neurological state and development.
▪ Brief (4–20 sec) and frequent (tens per day) absence seizures with abrupt and severe impairment of consciousness.
▪ EEG ictal discharges of generalized high-voltage spike and double (maximum occasional 3 spikes are allowed) spike- and slow-wave complexes. They are rhythmic at around 3 Hz with a gradual and regular slow down from the initial to the terminal phase of the discharge.
▪ Other types of seizure, such as GTCS, or MJs, prior to or during the active stage of absences.
▪ Eyelid myoclonia, perioral myoclonia, rhythmic massivelimb jerking, and single or arrhythmic MJs of the head, trunk, or limbs. However, mild myoclonic elements of the eyes, eyebrows, and eyelids may be featured, particularly in the first 3 sec of the absence seizure.
▪ Mild or no impairment of consciousness during the 3 or 4 Hz discharges.
▪ Brief EEG 3- or 4-Hz spike-wave paroxysms of less than 4 sec, polyspikes (more than 3) or ictal discharge fragmentations.
▪ Visual (photic) and other sensory precipitation of clinical seizures.
▸ OIRDA is seen almost exclusively in children with epilepsy and it is rarely seen in children with diffuse encephalopathy.
▸ OIRDA is seen almost exclusively in children less than 10–15 years old and is associated with epilepsy, most commonly in IGE, especially absence epilepsy and, less commonly, focal epilepsy.
▸ The frequency of the occipital rhythmic discharges in children with absences was generally faster (3–4 Hz) than in localization-related epilepsy (2–3 Hz).24
▸ Diffuse 3-Hz rhythmic delta activity without spike component is an exceptional ictal EEG finding during the absence seizure.
▸ Alterations in normal thalamocortical reciprocal interactions are critical in the generation of the regular generalized spike-wave discharges characteristic of the IGEs.
▸ Most patients with unilateral thalamic lesion and epilepsy showed bilateral synchronous generalized spike-wave (GSW) discharges. Absence status with bilateral GSW discharges caused by ischemic lesion in the left thalamus was reported.
▸ Children with thalamic lesions should be monitored closely for ESES. Lesions of the inferior-medial-posterior thalamic structures might have a role in the pathogenesis of bilateral SW discharges and ESES by the mechanism of disinhibition, possibly through the GABA-ergic system of the zona incerta and its projections.
▸ Jeavons syndrome refers to idiopathic reflex epilepsy with eyelid myoclonia, eye closure sensitive seizure, and photosensitivity. Seizures are brief (3–6 sec). Ictal EEG consists of generalized PSW at 3–6 Hz, usually occurring after eye closure. Eyelid myoclonia is resistant to treatment.
