516463 research-article2014

EEGXXX10.1177/1550059413516463Clinical EEG and NeuroscienceLadino et al


A Unique Ictal EEG Pattern in a Patient with the Coexistence of Generalized and Focal Epilepsy

Clinical EEG and Neuroscience 2015, Vol. 46(2) 136­–141 © EEG and Clinical Neuroscience Society (ECNS) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1550059413516463 eeg.sagepub.com

Lady Diana Ladino1, Aaron Gleadow2, and José F. Téllez-Zenteno3

Abstract The coexistence of focal and generalized epilepsy is rare. We report on a 17-year-old male with drug-resistant focal epilepsy and idiopathic generalized epilepsy (IGE). He began to experience generalized tonic-clonic seizures (GTCS) at the age of 3 years, with a good response to phenobarbital. At the age of 14 years, he began to experience complex partial seizures (CPS). Videoelectroencephalography (video-EEG) telemetry showed the coexistence of right temporal spikes and bursts of generalized spike-wave (GSW). The ictal EEG showed a unique EEG pattern characterized by a 4- to 5-second burst of GSW followed by rhythmic delta activity over the right temporal region. A magnetic resonance image (MRI) showed right hippocampal sclerosis. The patient underwent a right temporal lobectomy that significantly improved his seizure control. He was rendered seizure free of the complex partial seizures and improvement of the GTCS. This case illustrates a very uncommon ictal EEG pattern, and shows that the decision for surgery in patients with focal drug-resistant epilepsy should not be affected by coexistent generalized epilepsy. Keywords classification, epilepsy surgery, idiopathic generalized epilepsy, seizures, temporal lobe epilepsy Received June 6, 2013; revised September 17, 2013; accepted November 19, 2013.



The current classification of the International League Against Epilepsy1 makes a distinction between epilepsy with a focal and a generalized onset. In generalized epilepsy, patients have simultaneous involvement of both sides of the body during seizures, and the EEG shows bilateral synchronous and symmetrical discharges. On the other hand, patients with localizationrelated epilepsies have focal semiology and EEG findings consistent with a localized onset for the seizures. Additionally, the International League Against Epilepsy1 points out that if a patient has focal and generalized seizures together, or in succession, with EEG showing focal and generalized findings, the distinction cannot be made. The coexistence of IGE and temporal lobe epilepsy (TLE) is a diagnostic and therapeutic challenge, especially if the seizures are resistant to antiepileptic drugs (AEDs), and the patient requires surgical treatment. We report a case with coexistence of focal epilepsy and IGE, with the patient achieving seizurefree status following an anterior temporal lobectomy. The main focus of this article is the description of a unique ictal EEG pattern in temporal epilepsy. In addition, we review the similar reported cases in the literature.

We present a patient with the coexistence of right TLE and IGE. The clinical history demonstrated 2 types of clinical seizures, and the EEG showed focal and generalized findings. Our patient underwent a temporal lobectomy with full resolution of the CPSs and improvement of the GTCSI. We also performed a comprehensive search for articles published from 1950 to 2013 using Medline, Embase, Index Medicus, Cochrane database, and bibliographies of pertinent reviews and original articles, to identify surgical cases with the coexistence of 1

Neurology Department, Hospital Pablo Tobón Uribe, Medellin, Antioquia, Colombia 2 Clinical Neurophysiology Laboratory, Royal University Hospital, Saskatoon, Saskatchewan, Canada 3 Division of Neurology, Department of Medicine, Royal University Hospital, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Corresponding Author: José F. Téllez-Zenteno, Division of Neurology, Department of Medicine, Royal University Hospital, University of Saskatchewan, 103 Hospital Drive, BOX 26, Room 1622. Saskatoon, Saskatchewan, S7N OW8, Canada. Email: [email protected] Full-color figures are available online at http://eeg.sagepub.com


Ladino et al Table 1.  Case Series of Patients With Partial and Generalized Epilepsy.

Prevalence (%)

Author (Year) 2

Niedermeyer (1968) Gabor and Marsan (1969)3 Sadler and Blume (1989)4 Geller et al (1995)5 Li et al (1996)6 Diehl et al (1998)7 Koutroumanidis et al (1999)8 Nicolson et al (2004)9 Jeha et al (2006)10 Wyllie et al (2007)11 Gupta et al (2007)12 Radhakrishnan et al (2011)13 Moseley et al (2012)14 Moseley et al (2012)15 Enatsu et al (2013)16 Total

Age in Years (Mean)

Surgical Treatment Seizure Febrile Family (No. of Surgical Free After Seizures (%) History (%) Patients) Treatment (%) Surgery (%)




14.5 30.3

17 35

ND 10

14.5 20






ND 5 ND 0.57

6 4 1 2

6 5 4 2

24 25 16 23

0.93 0.2 12 5.6 1.8

9 7 50 10 12

10 12 1 2 9

3.4 ND ND 5

21 1 1 190

6 1 10 6.5

5.8 0

ND 11.4

2 0

12 0

100 —





ND 50 100 100

ND 50 100 ND

2 4 1 2

33 100 100 100

100 50 0 50

ND 26 8 9 21

11 57 ND ND 83

0 57 ND ND 8.3

1 4 50 10 12

11 57 100 100 100

100 100 72 80 66

28 11 13 18.6

48 0 0 41

9.5 0 0 24

21 1 1 125

100 100 100 66

57% Engel I-II 100 100 92 (74%)

Abbreviations: SO, seizure onset; ST, surgery time; ND, not described; POP, postoperative.

focal and generalized epilepsy. We used the following words: generalized epilepsy, focal epilepsy, partial epilepsy, temporal epilepsy, EEG, electroencephalogram, coexistence, concurrence, simultaneous, bisynchronous spike-waves, and epilepsy surgery. Of 170 references, 48 potentially eligible articles were reviewed in full text, and 15 fulfilled eligibility criteria and were included in the analysis. We selected only cases and reports of patients with generalized and focal findings demonstrated with EEG (Table 1). We ruled out cases with bilateral secondary synchrony.

Results Case Summary A 17-year-old right-handed male was referred to our epilepsy clinic with a remarkable family history of epilepsy (grandfather, grandmother, an aunt, and a cousin, all have IGE). His medical history was unremarkable. He began to experience GTCSs at the age of 3 years. All seizures lasted between 1 and 2 minutes; they began with loss of consciousness followed by symmetrical tonic-clonic movements in the 4 limbs. He never experienced focal clinical symptoms, or signs, before the age of 14 years. He was placed on phenobarbital, and despite treatment he experienced between 6 and 7 GTCSs per year. At the age of 14 years, he began to experience daily CPSs. He experienced an aura described as “something strange is happening,” followed by staring spells, associated with oral automatisms

and loss of awareness lasting 60 seconds. The patient had postictal confusion with rare secondary generalization. Seizure control was not achieved despite trials with 8 standard AEDs alone and in combination. A neuropsychological evaluation showed overall, normal cognitive functions. MRI revealed atrophy of the right hippocampus, with an increased signal on T2-weighted and FLAIR images consistent with a right mesial temporal sclerosis (MTS). Scalp video-EEG monitoring revealed normal background activity with spikes over the right temporal region, maximum at F8 and T4, and also frequent bursts of GSW with a bifrontal predominance (see Figure 1). Nine complex partial seizures were recorded in the telemetry, and all had a clear right temporal onset. All ictal events had a similar EEG pattern; the onset was characterized by bursts of GSW lasting between 4 and 5 seconds, followed by rhythmic, focal delta over the right temporal region (maximum at T4, T6, FP2). In the postictal phase, focal delta was present only in the right temporal region (Figure 2). Based on presurgical evaluation, we concluded that the patient not only had IGE but also focal symptomatic epilepsy due to the focal EEG features and the presence of MTS. Given the intractability of his focal epilepsy he underwent right temporal lobectomy at the age of 18 years. Histopathology revealed severe neuronal loss and gliosis involving predominantly the hippocampal sector CA1 and the dentate, consistent with MTS. His seizures improved significantly after epilepsy surgery. After 5 years of follow-up, he has not had any CPS and has only had 3 tonic-clonic seizures, always associated with lack of compliance of AED regimens.


Clinical EEG and Neuroscience 46(2)

Figure 1.  (A) This scalp EEG recording shows interictal generalized epileptiform discharges, consisting of 2- to 3-Hz spike and wave with a frontal predominance. In the same trace we can observe a spike over the right mid-temporal region (maximum T4). (B) This trace shows first a sharp wave over the right temporal region and then a burst of generalized spike wave at the end of the page.

Since surgery, the post-resection EEGs have shown slowing over the right temporal region, no focal spikes, and sporadic bursts of GSW (less frequent than before the surgery). Because of the presence of generalized epileptiform activity, medications have not been withdrawn after surgery. His current medications are Lamotrigine 250 mg twice a day and Levetiracetam 500 mg twice a day. The dose of medications has not been modified after surgery.


Figure 2.  (A) This figure shows one of the complex partial seizures recorded with video-EEG telemetry. The onset is characterized by bursts of generalized spike-wave (GSW), lasting 5 seconds, with a frequency of 2 Hz. At the end of the figure it is possible to identify rhythmic delta over the right temporal region maximum at F8 and T4. (B) This figure shows the progression of the seizure characterized by rhythmic theta and delta, maximum at F8-T4, with no generalized epileptiform activity. (C) Finally, this figure shows the postictal period where a focal delta is maximum at F8-T4.

In our literature review, we found 190 patients in 15 articles. The vast majority of studies were retrospective and originated from epilepsy centers. The mean prevalence of cases with focal and generalized epilepsy was 5% (0.2% to 14.5%). It is considered a rare phenomenon even in specialized centers. In our center, the prevalence of these cases is 1% (7 cases in 700 patients). Among all our patients, this is the only one who underwent surgery. The relative infrequency of these cases may reflect some degree of underdiagnosis because epileptologists are usually focused on patients with partial epilepsy who could be potential candidates for surgery. Furthermore, the coexistence of focal and generalized epilepsy can be difficult to diagnose in some patients. Clinical myoclonic jerks, especially when they are asymmetric, may be mistaken for focal motor seizures, whereas, typical absences particularly associated with mild automatisms can be misdiagnosed as limbic CPS.8

This coexistence of focal and generalized epilepsy is more commonly reported in the pediatric population.9,10 Gabor and Marsan3 reported 35 cases whose mean age was 18.6 years (range 8-28 years), and the mean seizure age onset was 6.5 years (range 1-12 years). Our case had an early seizure onset similar to the study by Gabor and Marsan.3 He also had TLE, which is the most common type of focal epilepsy associated with IGE.2,6,8-10,16 Some authors have reported that frontal epilepsy is more frequently associated with generalized epilepsy than temporal epilepsy.3 Our patient had a strong family history of epilepsy, with several family members affected with IGE since childhood. Li et al6 reported that a family history of epilepsy is a common characteristic of patients with the coexistence of focal and generalized epilepsy, and its presence can be as high as 24%. Our


Ladino et al patient did not have febrile seizures, another common reported risk factor.6-8,10 Some studies have reported prevalence of febrile seizures between 41% and 83%.6-8,10,13 Remote febrile seizures and a positive family history should alert physicians to the possibility of the coexistence. Electrographical findings that suggest the coexistence of generalized epilepsy in patients with focal epilepsy are the presence of slow background rhythms,3 photo-paroxysmal response,9 and generalized interictal discharges with hyperventilation.4,6 Gabor and Marsan3 reported 35 patients with coexisting focal and generalized epileptiform discharges. They compared the EEG findings of these patients with 65 control patients with only focal epileptiform activity. The study found that slowing of the background activity during wakefulness was present in 71% of patients with bisynchronous discharges and in only 30% of the control group (P < .001). In the majority of the patients the slowing was diffusely distributed over both hemispheres. Our case did not have these findings. Different ictal patterns have been described through history. In 1978, Geiger and Harner17 pointed out that focal hypersynchrony on the scalp EEG was an accurate localizing indication of cortical irritability. In 1996, Ebersole and Pacia18 described 3 different ictal rhythms in TLE. Type I is characterized by rhythmic 5- to 9-Hz theta activity that slowly evolves and remains localized to the temporal or subtemporal regions. It is the most specific pattern for seizures originating from the hippocampal areas. The Ebersole type II is characterized by rhythmic slow activity (2-5 Hz) with widespread temporal distribution. It is frequently associated with neocortical seizures. The Ebersole type III is characterized by diffuse ictal EEG changes or attenuation without clear lateralization. This pattern can be seen in hippocampal and temporal neocortical seizures. In the same year, Atalla et al19 described a special ictal pattern called start-stop-start phenomenon. Atalla et al19 found this pattern, using sphenoidal electrodes, in 13% of patients with TLE. The first “start” usually has a narrow field, typically in the sphenoidal electrodes. The mean duration of the “start” is 11 seconds, and usually the clinical onset correlates with these changes. The stop lasts 8 seconds, and the restart often had a different morphology, frequency, and a wider field. Atalla et al19 stated that the restart can be misinterpreted as the actual seizure onset. Other TLE ictal patterns include focal or regional background attenuation.20 Multiple scalp EEG expressions of TLE are likely a consequence of several factors, including the following: the accurate location of ictal onset, the underlying pathology, and the routes and speed of seizure propagation. Our patient had a rare ictal pattern characterized by a burst of slow frequency (2 Hz) GSW discharge lasting 5 seconds, followed by a clear rhythmic delta over the right temporal region. We recorded 9 CPSs and all of them had a similar EEG pattern. It is hard to explain the initial changes characterized by GSW; they could be related to an alteration of thalamic and temporal networks. An intact thalamocortical circuitry is required for the generation of typical spike-wave discharges.21 Spike-wave activity is rapidly synchronized, propagating via corticocortical networks from the

focal cortical site of origin, and the thalamocortical loop functions as an oscillatory network, with the 2 structures driving each other, resulting in amplification and sustenance of the discharges.22 The improvement of focal and generalized seizures in this patient after surgery was probably related not only to removal of the abnormal temporal region but also to the potential modification of an abnormal corticothalamic network where the temporal region had a critical role in the generation of seizures. Our patient underwent successful temporal lobectomy, with a full resolution of CPSs and improvement of generalized seizures. In the cases reported in the literature,2-16 125 out of 190 (65.7%) patients underwent surgery for focal refractory epilepsy. Ninetytwo out of 125 (73.6%) were seizure free after surgery. Many studies have documented seizure freedom rates ranging from 50% to 100% in these patients.8-10,13 A study in adults reported by Moseley et al14 evaluated long-term surgical outcomes in 21 patients with TLE and presurgical generalized interictal epileptiform discharges. Following amygdalohipocampectomy, 12 patients (57%) had favorable outcomes (Engel classification I-II). This result is comparable to the rates found in patients without generalized abnormalities.11 Therefore; the decision for epilepsy surgery should not be affected by the coexistence of IGE. Older series23,24 have reported that the presence of GSW is associated with higher risk of nonremission after surgery, although some recent studies4,6,10,11,14 have reported that the presence of generalized interictal discharges in patients with TLE is not a factor associated with lower rates of seizure freedom after surgery. Diehl et al7 reported an interesting case of a 16-year-old female, with TLE and hippocampal sclerosis, who underwent a right temporal lobectomy resulting in complete remission of CPSs. Eight months after surgery, she developed generalized myoclonic jerks, and video-EEG revealed abundant generalized poly-spike and GSW complexes. The authors suggested that the surgical resolution of her localization-related epilepsy somehow enabled the clinical expression of her genetic generalized epilepsy. Some studies have reported the presence of focal EEG abnormalities in patients with generalized epilepsy, specifically in patients with juvenile myoclonic epilepsy. Aliberti et al25 described the presence of focal epileptiform abnormalities (focal onset of generalized discharges, focal slow waves, and focal spikes) in 12 of 22 patients (54.5%) and in 18 of 49 EEGs (36.7%). Jayalakshmi et al26 reported focal EEG abnormalities in 92 of 266 (35%) patients with juvenile myoclonic epilepsy.

Physiopathology The pathophysiological mechanism underlying the coexistence of both types of epilepsy remains unknown. The common clinical features reported in these patients are early onset of seizures, young age, strong family history, and febrile seizures (among others), suggesting a simultaneous involvement of multiple genes to explain different seizure phenotypes.27 Other authors10,13 have suggested a link with the syndrome of generalized epilepsy with febrile seizures plus (GEFS+). Furthermore,

140 coexistence of 2 different types of epilepsies, usually starting with generalized epilepsy and followed by focal seizures, as with our patient, can be associated with a potential kindling phenomenon; where new focal structural changes in the cerebral cortex may be triggered by recurrent seizures.25 There is a hypothetical mechanism termed secondary temporalization, where paroxysmal activity with a centroencephalic origin might secondarily produce new epileptogenic areas in cortical areas with a low-threshold like the temporal regions. Although it is presumed to occur only in the context of generalized convulsions, it may also occur with nonconvulsive disorders, such as absence seizures.28,29 Our patient started having GTCSs in early childhood and then developed CPSs as an adult, suggesting potential kindling.

Conclusions The coexistence of IGE and partial epilepsy is uncommon, occurring in 5% of patients from epilepsy centers. Clinical characteristics and EEG features of both types of epilepsy occur in the same patient. A careful assessment of clinical semiology, EEG, and MRI is necessary to correctly diagnose these patients. In many with generalized epilepsy, the presence of MRI focal abnormalities is the main element to suspect coexistence with focal epilepsy. There are some clinical features to take into account in the potential diagnosis, such as early onset of epilepsy, young age at diagnosis, a strong epilepsy family history, and febrile seizures, as well as some electrographical features, such as the presence of diffuse slowing, activation of epileptiform activity during hyperventilation and photo-paroxysmal response. We described a new ictal EEG pattern characterized by GSW followed by rhythmic focal temporal delta. Finally, surgery should be considered for those cases with drug-resistant focal-onset seizures despite the coexistence of generalized epilepsy. Declaration of Conflicting Interests The author(s) declared no conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding Dr. Tellez-Zenteno receives grants from the University of Saskatchewan, the Royal University Hospital Foundation in Saskatoon, Saskatchewan, through the Mudjadik Thyssen Mining Professorship in Neurosciences and UCB Canada.

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A unique ictal EEG pattern in a patient with the coexistence of generalized and focal epilepsy.

The coexistence of focal and generalized epilepsy is rare. We report on a 17-year-old male with drug-resistant focal epilepsy and idiopathic generaliz...
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