Focal cortical dysplasia with prolonged ictal asystole, a case report.

INTRODUCTION: Cortical dysplasia carries significant morbidities such as seizures and delayed milestones. Focal cortical dysplasia (FCD) causes refractory epilepsy with various seizure types depending on the location and extent of the dysplasia. FCD in the temporal region and the insular cortex may cause ictal bradycardia (IB) and ictal asystole (IA). Video EEG (VEEG) with simultaneous EKG recording can better diagnose these cardiac abnormalities in FCD. We describe a case of refractory epilepsy. The patient's clinical seizures were usually followed by syncope. VEEG revealed frequent seizures some of which were associated with prolonged ictal asystole.
RESULTS: A 15 years old female was admitted to an epilepsy monitoring unit for VEEG. There were widespread fast abnormal discharges known as FREDs with a frequency of 16-20 Hz. She developed numerous habitual seizures and syncope. Some of these were associated with an EKG change in the form of asystole. The cardiac workup was normal. MRI revealed abnormalities in bilateral insular, temporal, and right parietal lobes.
CONCLUSION: This case highlights the significance of:●Fast rhythmic epileptiform discharges (FREDs) in cortical dysplasia.●Role of video-EEG monitoring.●Prolonged asystole and the potential role of cardiac intervention in the form of cardiac pacing and cardioneuroablation in decreasing syncope.

Introduction

Focal cortical dysplasia (FCD) is well known for its presentation as refractory epilepsy with various seizures types. Some of these seizures are associated with syncope or falls. It usually presents with refractory complex partial seizures (Guerrini et al., 1992a, Guerrini et al., 1992b). In about 8–12% of juvenile patients and infants, these abnormalities in cortical development are associated with developmental delay, poor cognition, and intractable epilepsies (Li et al., 1995, Semah et al., 1998). The FCD, in adults, usually manifests as seizures. One of the important causes of death in epileptic patients is a sudden unexpected death in epilepsy (SUDEP) that may incorporate the incidence of postictal bradycardia and postictal asystole (Tassi et al., 2002). The diagnosis of these cardiac abnormalities in a patient with refractory epilepsy especially with syncope can only be confirmed via simultaneous EEG and EKG recording (Novy et al., 2009). The confirmed diagnosis of FCD is done by histopathology however specific patterns in EEG are also important not only in diagnosis but in localization of the epileptic zone as well.

We report a child of FCD, identified by the specific EEG pattern known as focal rhythmic epileptiform discharges (FREDs) with a faster frequency of 16–20 Hz. Prolonged asystole of 23 s was observed in this case. To our knowledge, this is the longest asystole caused by cortical dysplasia.

Case presentation

A 15 years old school going, right-handed the girl was admitted to our epilepsy monitoring unit. She had a history of sudden episodes of absent-mindedness 3–4 times per day. Each episode lasted for several minutes. During a typical episode, the patient’s head would turn towards the left side; she would talk irrelevantly and respond poorly ending in sudden syncope. Episodes were stereotypic with several times injuries secondary to falls. There was no change in her seizure semiology for the last several years. In view of her frequent falls and syncope during seizures, her cardiac workup including EKG, echocardiography, Holter monitoring, etc was normal.

She had an abnormal postnatal history of severe neonatal hypoglycemia after a normal vaginal birth. Parents had noticed seizures since the age of five months. Her cognitive function test was normal but her school performance was poor due to refractory seizures. She was admitted to an epilepsy monitoring unit for seizure evaluation. Her medications included levetiracetam, lacosamide, clonazepam, and oxcarbazepine.

On examination, she was a cheerful young girl, cooperative and responding well to questions and commands. Her detailed neurological examination was unremarkable.

Her brain MRI scan revealed possible focal cortical thickening, agyria, and poor grey-white matter differentiation in bilateral insular, temporal, and parietal lobes (Fig. 1).

Fig. 1

MRI sequences of axial T1 (A & B), coronal FLAIR (C) and T2 (D) showing possible focal grey matter thickening with blurred grey and white matter differentiation involving various temporal and adjacent parieto-occipital lobes (arrow heads).

Her video EEG was performed with simultaneous EKG monitoring. During recording, there were intermittent abnormal focal fast discharges in the posterior aspect of the brain (mainly right temporo-occipital) both during awake and sleep state. These discharges were most likely FREDs (Fig. 2).

Fig. 2

A 10 s scalp EEG showing interictal, focal fast rhythmic epileptiform discharges(FREDs) (channel 8, 15 and 16) with amplitude (>100uV) and frequency o f 16–20 Hz in the posterior quadrants of the brain (predominantly right temporo-occipital with spread to the left occipital region).

During the VEEG there were multiple habitual seizures. These were typical with two of them having asystole and fall. In one such event, the EKG had baseline tachycardia that changed to bradycardia for 12 s and then followed by prolonged cardiac asystole lasting for 23 s. (Fig. 3, Fig. 4). During this period the patient was initially sitting on the bed, turned her head towards her left side, and started automatism of the right hand. This continued for several seconds until she fell down on the bed. There was complete asystole in EKG with complete body atonia. This was resumed by a normal cardiac rhythm. Simultaneous EEG demonstrated abnormal, rhythmic epileptiform discharges in the bilateral temporo-occipital regions, predominantly on the right side (Fig. 3).

Fig. 3

Two consecutive traces EEG in a habitual seizure with syncope and fall. First with rhythmic seizure activity starting in bilateral (predominantly right) temporo-occipital region and second with bradycardia followed by complete asystole for 18 s. Note the minimal cerebral activity during asystole consistent with clinical syncope and fall with complete loss of body tone as well.

Fig. 4

Two consecutive EEG tracings few seconds before the seizures, showing rhythmic epileptiform discharges arising from bilateral temporo-occipital regions.

Discussion

Abnormalities in cortical development in the form of FCD is associated with developmental delays, poor cognition, and intractable epilepsy in about 8–12% of the cases (Li et al., 1995, Semah et al., 1998). Such abnormalities are not only evident in MRI, but affected FCD patients also have certain EEG patterns. The phenomenology of abnormal discharges associated with cortical dysplasia is described with various forms and frequencies namely rhythmic epileptiform discharges (REDs), continuous epileptiform discharges (CEDs) (Gambardella et al., 1996) and focal fast rhythmic epileptiform discharges (FREDs) (Kuruvilla and Flink, 2002). Our patient’s discharges are most likely FREDs but with higher frequencies of 16–20 Hz and having a discrete localization (Fig. 2). The high amplitude fast rhythmic activity associated with sharp waves were considered highly specific for severe cortical dysplasia by Quirk et al. (Quirk et al., 1993).

FCD can involve any region of the brain, including the temporal, insular, orbitotemporal, or parietal lobes with peculiar EKG abnormalities including bradycardia and asystole. FCD with a prolonged IA is less defined (Seeck et al., 2003, van der Lende et al., 2016). For the diagnosis of these cardiac abnormalities in a patient with cortical dysplasia with syncope, simultaneous EEG, and EKG recording is essential (Novy et al., 2009). The initial localization depends upon the MRI however the exact ascertainment of the epileptic zone is only possible with VEEG, occasionally including invasive EEG as well (Tassi et al., 2002).

The abnormal cortex in our patient is most likely the initial triggering zone. During the habitual seizure of the patient, there was rhythmic activity in the bilateral temporo-occipital regions (right more than left) followed by ictal asystole (Fig. 3, Fig. 4). This was a prolonged IA lasting for 23 s. IA is a relatively benign condition as compared to the post ictal asystole (van der Lende et al., 2016). This is a self-limiting phenomenon that is not reported as one of the potential causes of death in SUDEP, yet we believe a prolonged IA could potentially be dangerous. The danger of prolonged IA needs to be investigated further. In our case, the reason for the complete body atonia with syncope is IA, which increases the morbidity of the patient. (Ghearing et al., 2007) (Fig. 3, Fig. 4). Moreover, both semiology and the abnormal EEG the pattern indicated this was purely seizure activity rather than a primary cardiac event.

When a specific region of the brain, most likely left insular cortex, is stimulated electrically, this produces bradycardia and asystole (Oppenheimer et al., 1992). Besides the role of the insular cortex, areas of the temporal and frontal cortices should also be considered for symptom generation because the pathomechanism of IA is still unknown. Moreover, autonomic control of the heart rate may not be the same in all individuals (Reeves et al., 1996); it can be shifted to an atypical location in the brain by certain pathology (Leung et al., 2006). This is of interest because, despite identical semiology, only two seizures were associated with cardiac events. This could represent a different region of onset or spread to the adjacent posterior insular cortex that further propagates the initiation of bradycardia and asystole. In other words, focal epileptogenic lesions in one region mostly involve other distant structures, thus making an overall network of epileptogenic zones, especially in cases of FCD (Aubert et al., 2009).

In our patient's history, there are short intervals of disorientation, lack of awareness, or seizures that can best be explained by the frequent interictal FREDs; however, the true disruption to her functioning was the prolonged seizures with complete body atonia and syncope that the VEEG captured. The VEEG shows marked abnormal cardiac depressor responses during these prolonged seizures (Fig. 3, Fig. 4). This complete prolonged IA may necessitate further investigation regarding increased morbidity in this type of epilepsy with frequent syncope or body atonia. The role of placing a pacemaker for the ictal asystole is still controversial (Kepez and Erdogan, 2015), but Shihabuddin et al observed significant improvement and decrease in syncopal attacks mediated by ictal bradycardia and IA after insertion of cardiac pacemakers (Shihabuddin et al., 2014). Another relatively newer and successful option is cardioneuroablation that was first described by Pachon et al. in 2005. The procedure was performed successfully by Antolic and colleagues on a patient who did not suffer from IA again after the procedure (Antolic et al., 2018, Pachon M et al., 2005). In the light of above facts, cardiac intervention seems to be optimistic. It may help patients who are refractory to AEDs and need long-lasting relief from their illness (Reeves et al., 1996, Strzelczyk et al., 2008).

Conclusion

This case clearly highlights:

Various clinical, EEG, and MRI presentations of cortical dysplasias.

Fast rhythmic epileptiform discharges (FREDs) in cortical dysplasia.

The superiority of VEEG in localization of the specific epileptic zone or a network secondary to the FCD.

The potential role of pacemaker, cardioneuroablation, and other ways to lessen the morbidity in the form of falls and syncope.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.